APPROACH TO THE ECG

 

Systematic Interpretation

Rate: Estimate by 300/number of small boxes between complexes (e.g., R waves); HR >100 = tachycardia, <60 = bradycardia

Rhythm: Regular or irregular QRS? Sinus: Regular upright P-wave in II/III/aVF/V₅/V₆, P before every QRS, QRS after every P

Axis: Heart rotates toward hypertrophy and away from ischemia; Look at lead I and aVF

 

I	aVF		Differential
+	+	Normal axis
+	−	Left-axis deviation	“physiologic,” LVH, LBBB, inferior MI LAFB, WPW
−	+	Right-axis deviation	RVH, RBBB, LPFB, WPW, lateral MI

Intervals: (1 horizontal big box = 200 ms = 5 small boxes, 1 small box

= 40 ms)

PR: Normal 120–200 ms (<1 big box); If >200 ms, 1st-degree AV block

QRS: Normal <100 ms; 100–120 ms → interventricular conduction delay (IVCD)

Territory: Septal (V₁), Ant (V₂–V₃), Lateral (V₄, I, aVL), Apical (V₅, V₆), Inferior (II, III, aVF)

 

Bundle Branch Blocks (if QRS ≥ 120 ms) (Circulation 2009;119:e235)
RBBB		1.  rSR’ in R precordial leads (V1, V2) 2.  Wide S-wave in I and V6

 

LBBB		1. Broad, slurred, monophasic R in I, aVL, V5 V6 (± RS in V5–V6 if cardiomegaly) 2. Absence of Q in I, V5 and V6 (may have narrow q in aVL) 3. ST and T-wave opposite major QRS deflection, LAD

QT: Measure from start of QRS to end of T-wave; correct for HR: QTc/

= QT/ Prolonged QT/QTc (>440 ms ♂, >460 ms ♀); DDx: Electrolytes, meds, congenital

Chamber size:

 

ECG P-wave criteria

Left Atrial Abnormality (LAA)

Right Atrial Abnormality (RAA)

LVH: Sokolow–Lyon: S in V₁ + R in V₅ or V₆ ≥35 mm, or R in aVL ≥11 mm

RVH: R > S in V₁ or R in V₁ ≥7 mm, S in V₅ or V₆ ≥7 mm

Ischemia (Circulation 2007;116:2634),

Q-waves (prior MI): Q-wave ≥20 ms in V₂–V₃ OR ≥30 ms and ≥1 mm in 2 contiguous leads ST elevations (STE): ≥1 mm ST elevation in any 2 contiguous leads except V₂–V₃, where it has to be ≥1.5 mm in ♀ or ≥2 mm ♂; DDx: LBBB, early repolarization, electrolytes, PE, Brugada ST depressions (STD): Horizontal or down-sloping ≥0.5 mm in 2 contiguous leads; DDx: Ischemia, LVH with strain, hypokalemia, digoxin T-wave Inversion (TWI): DDx: Ischemia, cardiomyopathy, abnl repolarization, electrolytes,

cerebral event If LBBB: STEMI by Sgarbossa’s criteria: STE ≥1 mm in lead with +QRS, or STD >1 mm in lead with—QRS, or STE

≥5 mm in lead with—QRS; paced rhythm precludes assessment New LBBB in setting chest pain/ischemic equivalent is STEMI until proven otherwise

 

SUDDEN CARDIAC DEATH

 

Background (Circulation 1998;98:2334; NEJM 2001;345:1473)

Definition: Unexpected natural death from a cardiac cause occurring soon (≤1 h, typically) after the onset of sx in an individual w/o other cause of death

Epidemiology: 300,000–400,000 cases/y, accounts for >50% of all cardiac deaths in US; in pts <35, usually 2/2 congenital heart disease; if

>35, usually due to CAD

Risk factors: CAD, CHF, inherited d/o (e.g., WPW, long QT) Pathophysiology: Predisposing condition (anatomic, functional) + transient factor (electrolytes, ischemia); primary arrhythmia is typically VF, VT, or VT → VF; bradyarrhythmias are thought to cause only 7% of SCD

Evaluation

Evaluation: Sx: Palpitations, chest pain, syncope (esp exertional syncope or syncope from a nonvagal mechanism), PMHx; CHF, CAD or s/sx of these; tx w/ QT-prolonging meds, FHx SCD, ventricular arrhythmia, structural heart disease

Exam: Signs of HF, valvular disease, hypertrophic changes, particularly HOCM

Initial workup: ECG (prior MI, conduction delays [incl LBBB, ↑QT], LVH, ventricular ectopy); TTE: If ↑ suspicion for heart failure or HOCM, stress test (if medium prob CAD—see Noninvasive Testing, or if indicated for sports clearance (see Sports Eval); further w/u per cardiology may include cardiac MRI for arrhythmogenic right ventricular CM (ARVC)

 

Inherited Disorders in Sudden Cardiac Death (Cardiology Consultation Advised)
HOCM: Asymmetric septal hypertrophy → outflow tract obstruction; prevalence of 1/500, yearly incidence of SCD of 2–4% in adults & 4–6% in children (NEJM 1997;336:775) ECG: LVH, STE, apical TWI, Q-wave in I, aVL, V4–V6; abnl ECG found in 95% of pts (JAMA 2002;287:1308)

 

 

WPW: Accessory tract bypasses AV node. In SVT (AFib esp), risk of rapid, 1:1 conduction down the bypass tract → VF ECG: Shortened PR interval & slurred upstroke of the QRS (delta waves)
Congenital Long QT Syndrome (LQTS): Mutations in Na or K channels → prolonged myocyte depolarization (↑ QT) → torsades de pointes; p/w syncope or may be asx ECG: Prolonged QT/QTc (>440 ms ♂, >460 ms ♀); pts w/ baseline QTc >500 are considered at high risk for SCD
Arrhythmogenic right ventricular dysplasia: Fibrous replacement of the RV>>>LV → arrhythmia; 2nd–4th decade of life; 50% with + FHx (NEJM 2017; 376:61). ECG: TWI in V1–V3, ε waves, RBBB, & prolonged QRS Cardiac MRI: E/o fatty infiltration, scarring, dilation/dysfunction of RV
Brugada syndrome: Mutations → ↓ Na current; may have ⊕ FHx ECG: Pseudo RBBB in w/ ST ↑ in V1–V3 (type 1) or a “saddle-back” morphology, most prominent in V2 (types 2 & 3); may be transient/only in context of inciting factors: Meds (antiarrhythmics, antidepressants, βB), fever, EtOH, cocaine, electrolyte disturbances
Acquired Disorders in Sudden Cardiac Death
Heart failure: Many pts w/ EF ≤35% qualify for ICDs; cards consultation advised (see “Heart Failure”).
Drug-induced QT prolongation: azcert.org contains a continually updated list of drugs known to affect the QT interval. If QT prolonged at baseline, d/c culprit medication
CAD or h/o MI: See “Coronary Artery Disease” for secondary prevention
Electrolyte abnormalities: Monitor Mg, K in pts with renal failure or on diuretics, especially if baseline ECG is abnormal (see “Potassium Disorders”)

 

CORONARY ARTERY DISEASE

 

Background (Circulation 2012;126:e354; NEJM 2012;366:54)

Coronary artery disease (CAD)/Ischemic heart disease (IHD): Signs, Symptoms, or complications of atherosclerotic deposition in the coronary vasculature; stable if sx controlled

Epidemiology: 1 in 2 ♂ & 1 in 3 ♀ will develop CAD (Circulation 2015;131:e29); CAD is the leading cause of death in US, responsible for 1 in 6 deaths (Circulation 2010;121:948)

Pathophysiology: Endothelial + intimal dysfunction, cholesterol deposition, foam cell accumulation → fatty streak; + inflammation → atheroma → fibrous cap formation & remodeling → calcification & plaque formation → stenosis (angina) or plaque rupture + thrombosis (MI ± HF or SCD) (Nature 2011;473:317; NEJM 2013;368:2004)

Risk factors: ↑ Risk: Smoking (2.9 OR), HLD, HTN (1.9 OR), DM (2.4 OR), obesity (1.1 OR), ↑ age, rheumatoid arthritis (RA) (3.1 ↑ RR), SLE, FHx of CAD, ♂ gender, HIV, XRT exposure, metabolic syndrome; CKD:

↓ GFR & ↑ proteinuria assoc w/ ↑ risk of CV events (Lancet 2010;375:2073); ↓ Risk: Daily fruits & vegetables (0.7 OR), regular EtOH consumption (0.91 OR), ASA, regular exercise (0.86 OR) (Circulation 2003;107:103; Lancet

2004;364:937; NEJM 2012;366:321)

Genetics: Complex inheritance assoc w/ multiple genetic loci (Nat Genet 2012;45:25) CAD risk equivalents: Carotid artery disease, PAD, AAA, DM, CKD

Definition of ⊕ FHx: MI or CAD death in 1° relative <50 y for ♂, <60

y for ♀

Women and CAD: Less likely than ♂ to have typical angina, & typically present at a later age than ♂ (Am Heart J 2006;151:813; Eur Heart J 2008;29:707)

CAD Presentations (Circulation 2012;126:e354)

Asymptomatic: Incidentally discovered on noninvasive testing

Stable angina: Substernal chest discomfort when myocardial O₂ demand > supply with characteristic quality that is provoked by exertion or emotional stress and relieved by rest or nitroglycerin; unstable angina occurs at rest or in escalating pattern

 

Acute coronary syndrome: Sx or asx (silent) disruption in coronary circulation detectable by ambulatory ECG or stress testing (ECG, TTE, or nuclear imaging); new Q-wave on ECG (Ann Intern Med 2001;135:801); risk of silent ischemia ↑ in DM & hypothyroid pts

Ischemic cardiomyopathy (CMP): EF ≤40% due to CAD Cardiac syndrome X/Microvascular angina: ♀ > ♂; angina + ST depression on ETT w/ nl angiography (NEJM 2007;356:830); due to microvascular CAD or hypersensitivity to cardiac pain (Circulation 2004;109:568); treated w/ βB, CCB, nitrates, reassurance

Evaluation

History: Assess for presence/quality of chest discomfort (see “Chest Pain”), presence of risk factors (above), activity level, DOE, diet, exercise, tob/EtOH use, FHx, depression & ED (often comorbid w/ CAD) (Circulation 2008;118:1768)

Risk estimation: Framingham risk model most commonly used in US; ASCVD risk calculator available (risk estimate includes CAD and stroke risk) at tools.acc.org/ASCVD-Risk-Estimator-Plus/

Diagnosis: Based on clinical history of angina in the presence of risk factors:

Noninvasive testing: See “Noninvasive Testing”

Coronary angiography: If high-risk noninvasive results (≥1 large or

≥2 mod size territories of ischemia on stress, or LV dilation), unexplained LV dysfunction, unable to undergo test, medically refractory angina, indeterminate noninvasive study

Workup: Waist circumference, BMI, lipids, & DM2 screening (see “Screening”); Holter useful in dx of silent ischemia, variant angina; may consider use of CRP & LpA for further risk stratification (Arch Intern Med 1997;157:1170; Circulation 2003;107:363; 499)

Coronary Artery Disease Prevention

 

Primary prevention                  Secondary prevention
Goal	Prevent disease	Prevent harm from disease
Exercise, healthy diet	X	X
Quit smoking, moderate EtOH	X	X
BMI 18.5–24.9, waist < 40″ ♂, 35″♀	X	X

 

Lipids at goal	X	X
DM well controlled	X	X
BP at goal (<140/90)	X	X
Aspirin	Based on risk of CVD, age	X (unless contraindicated)
ACE inhibitors/ARBs		DM2, HTN, MI, EF <40%, CKD
β-blockers		H/o MI or CHF

(AFP 2010;82:289; 2011;83:819; Circulation 2002;106:388; JACC 2006;47:2130)

Primary Prevention

Diet: ↑ Fruits, vegetables, fiber; ↓ red meat, trans fatty acid, sat fats, high-fructose corn syrup; stepwise 1–2 improvements q3–6mo may ↑ compliance (AFP 2009;79:571)

Mediterranean diet: ∼30% ↓CV events in high CV risk (NEJM 2013;368:1279); ↑ vegetables, locally sourced, min processed foods, ↓ red meat, <4 eggs/wk, moderate dairy, olive oil as main source of fat, moderate red wine, fresh fruit for dessert (AFP 2009;79:571) Vitamin supplementation: RCT do not demonstrate benefit of β- carotene, Vit C, or Vit E (JAMA 2005;294:56; 2008;300:2123; Lancet 2001;357:89; NEJM 1996;334:1145;1150); USPSTF does not recommend

vitamin supplementation in prevention (Ann Intern Med 2003;139:51) Diabetes, lipid, and blood pressure management; smoking cessation

Aspirin: In pts without known CAD, ASA ↓ risk of nonfatal MI (NNT =

162) but no mortality benefit & ↑ in bleeding (NNH = 73) (Arch Intern Med 2012;172:209); benefit of ASA must be weighed against risk of bleeding & incorporate pt preference (Ann Intern Med 2009;150:396; 405); bleeding risk likely to outweigh benefit in pts w/ Framingham 10-y risk score <10%; consider in pts w/ DM2 who have a 10-y CVD risk >5%, & in pts w/ CKD (Diabetes Care 2010;33:1395); Dose: 75–162 mg QD (ACC, AHA), 75– 100 mg QD (ACCP) (Chest 2012;141:e637s; JACC 2006;47:2130); in pts anticoagulated w/ warfarin, addition of ASA does not significantly ↓ risk of CV death, MI, & stroke (JACC 2003;41:62S)

 

USPSTF Recommendations for Aspirin in Primary Prevention of CAD (AFP 2016;94:660A)
Population	<50 y	50–59 y & ≥10%	60–69 y & ≥10%	≥70 y

 

		10-y CVD risk	10-y CVD risk
Recommendation	None given	Initiate aspirin	Shared decision making	None given

Secondary Prevention (Circulation 2012;126:e354; NEJM 2005;352:2524; 2007;357:1762)

Risk factor modification:

Diabetes: A1c goal <7% (avoid rosiglitazone)

Blood pressure: Goal per 2017 AHA/ACC guidelines <130/80

Lipid lowering (↓ LDL better): Mod–high potency statin; ezetimibe if statin intolerance Weight loss: BMI 18.5–24.9, waist circumference <40″ ♂, 35″ ♀

Exercise: 30–60 min of moderate-intensity aerobic activity 5–7x/wk

Smoking cessation: 36% reduction in mortality for pts with hx ACS (JAMA 2003;290:86) EtOH: limit ♀ to 1 drink/d; ♂ 1–2 drinks/d; Influenza vaccine

Aspirin: 75–150 mg QD or 325 mg QOD; ↓ CV morbidity & mortality by 20–25% (NEJM 2005;352:2524); variable absorption of enteric-coated ASA may ↓ effectiveness (Circulation 2013;127:377); clopidogrel in ASA intolerance

Bleeding risk: While ASA for CV protection assoc w/ ↑ risk of major GI (2.1 RR) & intracranial (1.7 RR) bleeds, absolute risk of bleeding is low (add’l 1.3 bleeds/1000 ASA treated pts compared to placebo) (Am J Med 2006;119:624); No difference between 75 and 325 mg/d in bleeding risk; in pts w/ hx GIB who must be on ASA,

1. pylori eradication + a PPI ↓ risk of rebleed (NEJM 2002;346:2033); ASA + esomeprazole superior to clopidogrel at ↓ risk of rebleed

(NEJM 2005;352:238)

ACE inhibitors: Pts w/ angina and CHF, DM2, CKD, HTN; meta- analysis of ACEI or ARB in pts w/ stable angina and a normal EF shows ↓ risk of overall mortality, nonfatal MI, CVA, and revascularization compared to standard medical Rx (AFP 2012;86:21) Cardiac rehab: Multidisciplinary program of exercise training, psychosocial support, nutritional/risk factor counseling; ↓ risk of MI, cardiac, & all-cause mortality (Am Heart J 2011;162:571); recommended by Medicare for pts w/ stable angina or who are s/p MI or CABG; Index of programs in US: www.aacvpr.org/Resources/Program-Directory

 

Sexual activity: Requires 4–5 METs (walking ∼4 mph on flat ground); sex ↑ HR & ↑ BP, causing pts to worry about triggering MI (Am J Cardiol 2000;86:27F; 51F); exercise training & medical Rx (ASA & βB) help mitigate risk; pts should wait 3–4 wk after MI & have a ⊖ ETT before resuming sexual activity (Am J Cardiol 2005;96:313)

Treatment of impotence: Reassurance in low-risk pts; PDE-5 inhibitors (sildenafil, vardenafil, tadalafil) contraindicated in pts on nitrates & α-blockers as can cause serious vasodilation/hypotension; should be used cautiously in pts w/ active ischemia, HF, low baseline BP, or on multiple BP meds

(JACC 1999;33:273)

CORONARY ARTERY DISEASE TREATMENT

 

 

Medical Management of CAD and Angina (Ann Int Med 2014;160:ITC1–16; NEJM 2016;374:1167)
Therapy	Considerations	Pathophysiology	Toxicities
βB	1st line; titrate to HR 55–60; compared to CCB, similar rate of MI/cardiac death, ↓ s/e (JAMA 1999;281: 1927). No clear survival benefit in angina	Bind to β receptors, ↓ O2 demand by ↓ HR & ↓ contractility, resulting in ↑ exercise tolerance, ↓ sx	HoTN, bronchoconstriction (safe in stable COPD), fatigue, nightmares, insomnia, worsening depression/ Raynaud’s (less so w/ β1-selective agents); taper rather than abrupt d/c due to w/d effects; antacids ↓ bioavailability of atenolol
CCB	May be used alone if βB contraindicated (i.e., bradycardia) or in combination w/ βB if sx not controlled by βB alone	Vasodilate & reduce contractility (NEJM 1982;307:1618)	Edema; verapamil & diltiazem may worsen CHF & should be used cautiously in pts w/ sinus or AV node dysfunction; verapamil s/e include constipation

 

Nitrates	Long acting: used as 2nd line; combine with βB or in place Sublingual: Acute angina or ppx before activities	↑ Arterial & venous dilatation, ↓ preload, ↓ myocardial O2 demand (NEJM 1998;338:520)	Flushing, HoTN, HA, syncope, nausea; tolerance; contraindicated in pts on sildenafil or w/ HOCM. Tachyphylaxis; 12– 14 h nitrate-free interval (usually at night).
Ranolazine	↓ Angina in pts w/ continued sx on βB, CCB, or nitrates	Works by ↓ Ca overload in ischemic myocytes	QTc prolonging; contraindicated in cirrhosis

 

Coronary Angiography & Revascularization (Circulation 2014;130:1749; JAMA 2013;310:2086; NEJM 2016;374:1954)

Indications: (1) Sx limit activities despite optimal medical Rx; (2) Pts do not tolerate medical Rx; (3) High likelihood of severe CAD based on noninvasive assessment (i.e., >50% left main disease, large area of myocardium at risk for ischemia)

Percutaneous coronary intervention (PCI): Includes stenting & balloon angioplasty (w/o stenting); preferred for 1 or 2 vessel disease w/o left main involvement, or in pts who are not surgical candidates; consider for highly select & stable pts w/ left main disease Bare metal stent (BMS): ↑ Restenosis compared to DES; requires a minimum of 1 mo of dual antiplatelet Rx compared to 3–6 mo for DES, ∴ BMS preferable in pts at ↑ risk for bleeding, noncompliance, or antiplatelet interruptions for procedures (NEJM 2007;356:984) Drug eluting stent (DES): Drug impregnated in stent is slowly released, ↓ neointimal growth & restenosis → less susceptible to restenosis in 1st y compared to BMS, but requires compliance w/ >3 mo of dual antiplatelet Rx due to ↑ risk of stent thrombosis 2/2 to delayed endothelialization compared to BMS (NEJM 2013;368:254)

CABG: (1) >50% stenosis in LM (↑ survival); (2) Diffuse 3 vessel disease (>70% stenosis) w/ large area of myocardium at risk or EF <40%; (3) Proximal LAD + another major coronary artery, or pts who are not PCI candidates; greatest benefit if LIMA–LAD

Medical Management Following Revascularization for MI (Circulation 2013;127:529)

In addition to secondary prevention medications in table above:

Antiplatelets: ASA + thienopyridine or ticagrelor for 12 mo (regardless of stent) ACEI: For pts w/ anterior STEMI, CHF, EF

<40%; consider for all STEMI survivors; use ARB in pts intolerant of ACEI Aldosterone antagonist: For pts already on an ACEI + βB & w/ EF <40%, sx CHF

βB: Continue for at least 3 y & consider indefinitely (Circulation 2011;124:2458) NTG: Pts should be instructed on PRN use & when to

 

seek medical attention

 

Antiplatelet Therapy (JACC 2016; 68:1082)

After CABG: ASA (75–100 mg QD) indefinitely + clopidogrel, may improve graft patency (JACC 2011;57:1639)—or ASA 325 mg QD for 9–12 mo depending on surgeon preference

Balloon angioplasty w/o stenting: ASA indefinitely (75–100 mg QD) + clopidogrel (75 mg QD) for 1 mo (Chest 2012;141:e637S)

PCI (DES/BMS) for stable angina: ASA (75–100 mg QD) indefinitely + clopidogrel (75 mg QD) OR prasugrel (10 mg BID) OR ticagrelor (90 mg BID) for a minimum of 1 mo (BMS) or 3 mo (newer DES). ≥12 mo preferred if ischemic > bleed risk (DAPT Score: tools.acc.org/DAPTriskapp; JAMA 2016;315:1735) as risk of MI, predominantly, unrelated to stent, persists until at least 30 mo post PCI (Circulation 2017;135).

*Indefinite clopidogrel: Shared decision for indefinite clopidogrel in PCI patients (DES or BMS), especially if at risk for catastrophic consequences from stent thrombosis (i.e., left main or proximal LAD stent) (NEJM 2014;371:2155); cardiology consultation advised

Warfarin + dual antiplatelet Rx (i.e., ASA + clopidogrel) – “Triple therapy”: If warfarin is needed for AF, mechanical valves, hx DVT, etc., use ASA 81 mg QD (JACC 2008;51:172); If w/ stent, consider stopping ASA after 1 mo (Lancet 2013;381:1107)

Mgmt of bleeding risk for dual antiplatelet (DAPT) Rx: Pts w/ hx GI bleeding: Use PPI; pts w/ GIB risk: Consider PPI in elderly, warfarin, steroids, NSAIDs, or H. pylori infection

Before elective noncardiac surgery: Elective noncardiac surgery should be delayed for 30 d after BMS, 3 mo after DES. Cardiac consultation advised if DAPT must be held. If DAPT held, restart ASA ASAP and then 2nd antiplatelet agent

 

 

CHEST PAIN AND NONINVASIVE TESTING

Background (AFP 2011;83:603; Circulation 2003;107:149; JAMA 2002;288:2745; NEJM

1979;300:1350)

Epidemiology: 6 million pts present w/ chest discomfort each year in US; Dx for pts presenting to PCPs: Musculoskeletal (36%), GI (19%), CV (16%), nonspecific (16%), psychiatric (8%), pulmonary (5%); Dx of CV disease ↑↑ in pts presenting to ER (54%)

Pretest probability of coronary artery disease: Stress testing indicated for pts w/ intermediate pretest probability (discussed below)

Definite/“classic” angina: (1) Substernal chest discomfort; (2) provoked by exertion/emotional stress; (3) relieved by rest/nitroglycerin “Atypical”/probable angina: Chest discomfort

 

w/ 2 of the 3 features of definite angina Nonischemic chest discomfort: ≤1 of the 3 features of definite angina

 

Pretest Probability of CAD
Age (y)	Sex	Typical/Definite	Atypical	Nonanginal	Asymptomatic
30–39	M	Intermediate	Intermediate	Low	Very low
	F	Intermediate	Very low	Very low	Very low
40–49	M	High	Intermediate	Intermediate	Low
	F	Intermediate	Low	Very low	Very low
50–59	M	High	Intermediate	Intermediate	Low
	F	Intermediate	Intermediate	Low	Very low
60–69	M	High	Intermediate	Intermediate	Low
	F	High	Intermediate	Intermediate	Low
Definition of probabilities: High >90%, intermediate 10–90%, low <10%, very low <5% ↑ pretest probability: DM2, HLD, smoking, Q-waves, or ST abnormalities

 

Differential Diagnosis of Chest Discomfort
	Diagnosis	Clues (AFP 2013;87:177)
Cardiovascular	Angina	Typically discomfort/pressure/burning/squeezing brought on by exertion, ↓ by rest or NTG; may radiate to jaw, neck, shoulder, arm, ± diaphoresis, nausea, paresthesias; levine sign (fist over chest)
	Unstable angina	Angina that is new-onset, worsening, or occurs at rest
	Diagnosis	Clues (AFP 2013;87:177)
Cardiovascular	Coronary vasospasm	Rest angina that abruptly resolves
	Aortic dissection	“Ripping or tearing” pain radiating to back, >20 mmHg difference in BP between arms, widened mediastinum on CXR. Loss of pulses; may be associated with new neurologic deficit or syncope.
	Pulmonary embolus	Dyspnea, tachypnea, tachycardia, hypoxemia, ± sudden pleuritic pain; H/o immobility, clotting, malignancy; ECG S1Q3TWI3.
	Pericarditis	Pleuritic discomfort worse supine, relieved by

 

		sitting forward; friction rub, diffuse ST elevation, PR ↓
	Myocarditis	Recent URI or flu-like illness → CHF; younger pts
	Valvular heart disease	Progressive angina/dyspnea, syncope
	Pericardial tamponade	↓ voltage ECG, electrical alternans, ⊕ pulsus
Pulmonary	Pneumonia	Fever, chills, cough, sputum, pleuritic pain, consolidation on chest exam; ⊕ CXR
	Pneumothorax	Acute onset pleuritic pain, dyspnea; ↓ breath sounds
	Pleurodynia	Chest pain from URI or coughing; Precordial catch syndrome is sudden pleuritic pain relieved by deep breathing thought caused by folding of pleura on itself
	Pulmonary HTN	Exertional dyspnea, fatigue, peripheral edema
GI	GERD	Burning brought on by eating, relieved by antacids; acid taste, dyspepsia, regurgitation
	Esophageal spasm	May respond to NTG; Provoked by swallowing
	Esophageal rupture	Mediastinal air on CXR, h/o vomiting/instrumentation.
	Other	Cholecystitis, pancreatitis, biliary & peptic ulcer disease
Other	Muscular pain	Pain w/ palpation, h/o injury, strain, repetitive use
	Rheumatic (fibromyalgia, rheumatoid/osteoarthritis)	Pain in other joints/tender points, h/o RA, OA, fibromyalgia
	Shingles	Dermatomal distribution, rash
	Psychiatric/anxiety	H/o φ problems, anxiety, ROS often pan- positive
	Rib fractures, bone mets	H/o malignancy, trauma, coughing

Evaluation (AFP 2005;72:2012; JAMA 2005;294:2623)

History: OPQRST—Other sx (diaphoresis, nausea, dyspnea), Provocative/Palliative factors (exertion, rest, breathing, eating, position), Quality (sharp, dull, throbbing, stabbing, pressure), Radiation/Risk factors, Severity (scale 1–10)/Site of pain, Timing: constant vs. intermittent, onset (abrupt vs. gradual), what were you

 

doing? Has this happened before?

Cardiac risk factors: Personal or FHx CAD (<55 y ♂ or <65 y ♀ in 1° relative), HTN, smoking, DM, obesity, HLD; exercise capacity (i.e., climbs stairs, runs) PE risk factors: Immobility, history of clotting, long plane/car rides, malignancy Other: Cocaine use, recent URI, hemoptysis, recent procedures/surgery

Atypical Presentations/Disparities: ↑ triage errors in women, minorities, elderly, diabetics, pts w/ dyspnea

Physical exam: VS: Including SaO₂ sat, BP in both arms (>10 mmHg difference → consider aortic dissection); ask patient to point where pain is; CV (JVP, heart murmurs, rubs, S₃, S₄, pulses), pulmonary (rales), abdominal (epigastric TTP), chest wall exam (TTP/reproducible), breast exam if sx; LE: edema, Homans sign

Diagnostics: CXR (PNA, widened mediastinum), ECG, labs (CBC,

electrolytes, D-dimer, troponin/CK per clinical suspicion); CT scan, stress testing (if intermediate pretest probability of CAD), TTE as needed

Management: Immediate ER referral of pts w/ life-threatening causes of chest pain (i.e., aortic dissection, pneumothorax, intermediate or high pretest probability for ACS or PE)

Patient information: JAMA 2009;301:1498; 2014;312:858; 2015;314:1990

NONINVASIVE CARDIAC TESTING

 

Indications

CAD diagnosis: Stress testing beneficial in pts w/ intermediate pretest probability of CAD to avoid false negatives in pts w/ ↑ pretest probability and to avoid false ⊕ in pts w/ ↓ pretest probability (NEJM 1979;301:230); see “Pretest Probability” table above; exercise ETT does not localize/quantify myocardial viability; pharmacologic/exercise imaging studies needed instead

Prognosis: In pts w/ stable angina after diagnosis or change in symptoms

Postrevascularization: Assess exercise tolerance & localize residual ischemia (need imaging)

 

Screening

Asymptomatic pts: In asx pts w/ low pretest probability, routine screening not recommended unless pt is in a high-risk occupation (e.g., airline pilots); risk eval using Framingham model w/ aggressive risk factor modification preferred (Ann Int Med 2016;164:479; NEJM 2003;349:465) Diabetes: No difference in cardiac events over ∼5 y in ASx DM2 pts who underwent adenosine-stress w/ imaging vs. no screening (DIAD

JAMA 2009;301:1547); ADA recs against screening ASx pts w/ DM2 (Diabetes Care 2012;35:S11); AHA/ACC recommends consideration of ETT in pts who plan to initiate vigorous exercise (JACC 2002;40:1531)

Prior to initiation of a rigorous exercise program: Consider exercise ETT in diabetics and in pts w/ intermediate or high risk of CAD

Pretest Counseling

To establish diagnosis of CAD as cause of symptoms: Hold βB, CCB, dipyridamole, and nitrates for 48 h and caffeine for 12 h prior to ETT/stress TTE (note: if concerns, d/w cardiology prior to testing); ACEI, statin ok to continue

To determine if known CAD is cause of current sx, for prognosis, or postrevascularization: Continue regular medications without interruption; βB/CCBs may limit ability to reach max HR

Choice of Test

Screening ECG: USPSTF & AHA recommend against ECG CAD screening in low-risk pts; insufficient evidence re: int/↑ risk pts (Ann Intern Med 2012;157:512; Circulation 2003;107:149)

ETT w/ ECG preferred for diagnosis, but may be limited due to arthritis, claudication, poor functional status, pulmonary disease, or inability to achieve 85% predicted maximal HR

Imaging studies (TTE or radionucleotide myocardial perfusion imaging [rPMI]) preferred in pts w/ prior PCI or CABG

Radionucleotide choice: Thallium detects viable myocardium; MIBI provides better images in ♀ or obese patients due to higher- energy photons, measures LVEF

“Stress testing”: Induces situation which (1) ↑ O₂ demand or ↑ coronary flow and (2) monitors for sx of ↓ supply; multiple combinations available; see table below

 

↑ Myocardial O₂ demand: Exercise (preferred, may be limited due to functional status, pulmonary disease, or inability to achieve 85% predicted max HR), chemical (adenosine, dobutamine) Monitor supply: ECG (often preferred, may be limited 2/2 abnl baseline

ECG such as LBBB); TTE or rPMI preferred for pts w/ prior

PCI/CABG

Ordering stress test: Choose stress modality (S) and ischemia assessment modality (I)

(S) Stress modality: Exercise (treadmill/recumbent bicycle) OR dobutamine OR vasodilator (adenosine, regadenoson, dipyridamole); generally, exercise preferred for diagnosis, but may be limited due to arthritis, claudication, poor functional status, pulmonary disease, or inability to achieve 85% max predicted HR

(I) Ischemia assessment: ECG +/– radionuclide myocardial imaging OR echo OR MRI; if pharmacologic (S) chosen, (I) must be an imaging modality (ECG not sufficient); TTE or rMPI preferred in pts w/ prior PCI or CABG, abnormal baseline ECG, or those who can’t exercise/need pharmacologic testing Radionuclide choice: Thallium detects viable myocardium; sestamibi (“mibi”) provides better images in ♀ or obese pts due to higher-energy photons, measures LVEF; assoc w/ 10–12 mSv (10x annual exposure in someone living at sea level; more than a diagnostic coronary cath); for comparison, US radiation workers allowed occupation exposure of ∼50 mSv annually)

Coronary artery calcium scoring: Screening in low-risk populations not recommended due to ↓ Sp and ↑ false ⊕ rate (AFP 2012;86:405; JACC 2007;49:378; JAMA 2014;312:837; NEJM 2012;366:294); consider ETT in pts w/

coronary calcium score >75th percentile

 

 

 

 

Features of Different Stress Testing Modalities (AFP 2007;75:2129)
Test	Comments
ETT ∼$160 (68% sensitive, 77% specific) (Ann Intern Med 1999;130:719; JAMA 2015;314:1968)	Pros: Standard test for most pts; cost-effective, widely available, gives functional capacity, prognosis, and provides information on pt symptoms; Cons: Requires exercise to 85–90% maximal HR (220-age in y); avoid if ECG shows WPW, V-paced, >1 mm ST↓ at rest, complete LBBB, LVH, or pt on digoxin; ECG changes in V1–V3 nondiagnostic in pts w/ RBBB; does not localize/quantify ischemia or myocardial viability; Contraindications: Recent MI (<2 d), unstable angina, symptomatic valvular heart dz, severe CHF/arrhythmias, myocarditis/pericarditis, aortic dissection, PE, systemic infections; left main disease (relative); Risks: 3.6 MI, 4.8 major arrhythmias, 0.5 deaths/10,000 ETT (Chest 1980;77:94)
Stress TTE ∼$375 (76–85% sensitive, 77– 88% specific) (JAMA 1998;280:913)	Pros: ↓ cost compared to nuclear imaging. Assesses functional capacity, EF, valve function, chamber size, myocardial viability, location, extent/severity of ischemia, & functional significance of CAD; Cons: Subjective interpretation, low-quality images in many pts, poor prognostic ability, avoid in LBBB, V-paced pts; ↓ sensitivity/specificity in LVH; ↑ false ⊕ in pts w/ HTN response to exercise, ↓ specificity w/ prior MI
Dobutamine TTE (80% sensitive, 84% specific)	Pros: No exercise involved, assesses myocardial viability, EF, chamber size, valve function, ↑ accuracy in pts w/ LBBB, best

 

(JACC 1997;30:595)	sensitivity/specificity of pharmacologic tests, may be used for prognosis after MI; Cons: Does not measure functional capacity, ↓ sensitivity for ECG Δs vs. ETT, subjective interpretation, risk of ventricular arrhythmia, contraindicated in aortic aneurysm, may cause coronary artery spasm; Risks: Rare (<0.2%) life-threatening complications (Am J Cardiol 2006;98:541)
Exercise rPMI (85% sensitive, 64% specific) (JAMA 1998;280:913)	Pros: Assess LV size, myocardial perfusion, functional significance of CAD, prognosis, & extent, location, & severity of ischemia, functional capacity, info on pt sx; ↑ accuracy w/ resting LV WMA; ↑ prognostic data compared to stress TTE; Cons: Cost, radiation exposure, variability between labs, high false ⊕ in pts w/ LBBB, or V-paced
Vasodilator (dipyridamole or adenosine) rPMI (89% sensitive, 75% specific) (Circulation 2003;108:1404)	Pros: No exercise involved, ↑ accuracy in pts w/ LBBB; Useful for dx and prognosis of CAD in pts unable to exercise. Cons: Does not measure functional capacity, ↓ Se for ECG Δs compared to ETT, pts must d/c theophylline 72 h & caffeine 24 h prior; risk of ischemia due to coronary steal w/ dipyridamole. ↓ accuracy w/ RV PPM, CCB, βB, nitrates. Contraindications: COPD/asthma, SSS, heart block; dobutamine rPMI may be used in pts w/ COPD or w/ adenosine/dipyridamole allergy
Coronary CT angiogram (Sensitivity ≥50% stenosis 85–98%, specificity 88–96% (Am J Med 2008;121:715)	Pros: AHA recommends against CTA screening in asx pts; may be useful in sx pts of int risk or w/ equivocal stress test results (Circulation 2008;118:586); useful to evaluate for anomalous coronary arteries Cons: Incidental findings (i.e., pulmonary nodules) ↑ pt anxiety and further diagnostic testing; radiation exposure. HR must be between 60 and 70 bpm or iv βB used. Pts w/ renal dysfunction, cardiac stents, severe calcification, and afib may be ineligible; cardiac MRI may be used in pts w/ contrast allergy or coronary artery calcification. (Am Heart J
	2006;151:404)

 

Testing Modality by Patient Characteristic (Circulation 2007;116:e418)
Patient Characteristic	Test Choice & Comments
Intermediate pretest probability (10–90%) w/o factors below	Exercise ECG treadmill test
WPW or >1 mm ST↓ at rest	Exercise perfusion or TTE
H/o PCI or CABG	Exercise perfusion or TTE
V-paced	Adenosine/dipyridamole rPMI
LBBB	Adenosine/dipyridamole rPMI, dobutamine TTE
Digoxin/LVH w/ <1 mm ST ↓	Exercise rPMI, TTE, or dobutamine TTE

 

Management of results: Cardiology consultation advised for intermediate-and high-risk stress test results; low-risk results may be medically managed

Patient information: Ann Intern Med 2012;157:1-38; JAMA 2008;300:1836

 

 

DYSLIPIDEMIA

Background (JAMA 2011;305:1086; NEJM 2005;353:1252)

Epidemiology: Dyslipidemia is a common problem affecting >1/3 of US adults; proper management can ↓ risk of stroke & CAD; high-risk pts receive greatest benefit from tx

Total cholesterol (TC) = LDL + HDL + VLDL (VLDL ≈ TG/5); formula valid if TG <400 mg/dL

Low-density lipoprotein cholesterol (LDL-C): “Bad cholesterol”; transports cholesterol to tissue; taken up by macrophages & endothelium → atheromas, endothelial dysfunction, & PLT aggregation → CAD/PAD; strong relationship w/ stroke/CAD risk: ↑ 30 mg/dL LDL → 30% ↑ in CAD

High-density cholesterol (HDL): “Good cholesterol”; HDL reverses cholesterol transport, removing it from tissue; ↓ HDL in familial syndromes, drugs (βB, BZD, steroids); ↑ HDL w/ aerobic exercise, wt loss, smoking cessation, diet; low HDL alone is not an indication to initiate drug treatment

Triglycerides (TG): Fatty acids from diet released by enterocytes into bloodstream; ↑ TG due to genetic disease, EtOH, smoking, DM2, obesity, hypothyroidism, pregnancy, medications (tamoxifen, CsA, βB, estrogens, PI)

Etiology: Most dyslipidemia 2/2 combination of diet, lifestyle, wt, & genetics

1°: Diet (saturated fat), sedentary lifestyle/obesity, heredity, ♂ gender, age 2°: Hypothyroidism, DM, nephrotic syndrome, CKD, EtOH, liver disease, medications (progestins, estrogens, anabolic steroids, corticosteroids, protease inhibitors, atypical

 

antipsychotics, retinoic acid derivatives, thiazides, βB, CsA) (Am J Cardiol 2012;110:823)

Screening: ♂ >35 y, ♀ >45 y; if risk factors for CAD then ♂/♀ >20 y; ✓

q5y if TC <200, more frequently if RFs or approaching tx threshold

Evaluation (Circulation 2014;129:S1; JAMA 2001;285:2486)

History: Lifestyle (activity), diet, ⊕ FHx premature CAD; risk factors (HTN, DM, smoking); presence or absence of clinical atherosclerotic cardiovascular disease (ASCVD): Includes ACS w/ or w/o resvascularization, CVA, TIA, & PAD; ask about muscle sx prior to statin Rx to establish baseline

Exam: BMI, carotid bruits, peripheral pulses, xanthoma, xanthelasma, corneal arcus

Labs: ✓ TC, HDL, LDL; HDL & LDL levels vary only 2–10% w/ fasting status; ∴fasting unnecessary unless info on TG (which vary up to 20% w/ fasting time) is needed (Ann Intern Med 2012;172:1707;1710); consider

• TSH, BUN/Cr, U/A (for nephrotic syndrome), A1c in pts w/ HLD

Monitoring therapy: If tx to target number, ✓ q6–8wk until goals reached, then q6–12mo; for most patients (tx based on CV risk assessment, not target lipid value), repeat only if clinically indicated q3–12 mo

Risk assessment: For those w/o known ASCVD, use Pooled Cohorts Equations Risk Calculator to predict 10-y risk of ASCVD events (defined as coronary death, nonfatal MI, fatal & nonfatal stroke) http://tools.acc.org/ASCVD-Risk-Estimator-Plus/ variables are age, gender, race, TC, HDL, DM, SBP, HTN Rx, smoking status

 

AHA Treatment Guidelines by Indication (Circulation 2014;129:S)
Indication	Recommendation/Notes
History of ASCVD	Pts ≤75 y: High-intensity statin Pts >75 y: Moderate-intensity statin
10-y ASCVD risk ≥7.5%, age 40–75 y	Moderate-or high-intensity statin
Diabetes, age 40–75 y	Moderate intensity statin If 10-y ASCVD risk ≥7.5% → high-intensity statin
LDL-C ≥190 mg/dL	High-intensity statin

 

Treatment (AFP 2011;84:551; Circulation 2014;129:S1; NEJM 1999;341:498)

General approach: Tx aim is to ↓CV risk; lifestyle & statins are primary tx;

ACC/AHA 2013 guidelines (Circulation 2014;129:S1) moved away from treating to target LDL; current paradigm is that initiation & intensity of therapy is dictated indication & calculated ASCVD risk Patients with LDL >190 mg/dL: Consider familial combined hyperlipidemia (1–2% population) or familial hypercholesterolemia & lipid specialist referral

Lifestyle: Aerobic exercise 30 min 3–4×/wk; some benefit after ∼6–12 mo; wt loss (2% wt loss ≅ 6% ↓ in LDL)

Diet: ↓ LDL ∼13% (JAMA 2011;306:831); ↑ fruits/veg, ↓ saturated fats & trans-fatty acids, 50% of total calories from complex carbs; AHA diet (heart.org); nutrition referral

Statins: HMG-CoA reductase inhibitors; ↓ cardiac & overall mortality in pts w/ or w/o CAD

Timing: QHS (liver cholesterol synthesis mostly at night when dietary intake lowest) Contraindications: Pregnancy (category X), breastfeeding

S/e: HA, nausea, (0.5–2%), sleep disturbance; ↑ LFTs

Muscle toxicity: Common (5%), may be bothersome but not dangerous; can be managed w/ reassurance, counseling, exercise, trial of alt statin; placebo effect may contribute (∼25% of pts reported myalgias w/ placebo alone in recent statin trial) (JAMA 2016;315:1580); true rhabdomyolysis/myositis rare (0.1–0.5%, ↑ risk if CKD, hypothyroid, >65 y, or given w/ gemfibrozil, macrolides, itraconazole, HIV PIs, or CsA) (JACC 2002;40:567); fluvastatin & pravastatin have lowest risk of muscle injury Interactions: Digoxin, warfarin grapefruit: Up to 8 oz or ½ a fruit QD OK

Monitoring: Baseline LFTs & CK; LFTs 12 wk after start; no need to re ✓ LFTs/CK unless per sx; d/c if CK >10× or LFTs >3× ULN

Pleiotropic effects: Atherosclerotic plaque stabilization/reduction (JAMA 2007;297:499), anti-inflammatory; no benefit in cancer prevention, conflicting evidence about prevention of dementia and increased risk of cognitive dysfunction

 

 

Statin Intensity and Dosing Recommendations
Statin intensity	High		Moderate	Low
Atorvastatin	40–80 mg		10–20 mg
Fluvastatin			80 mg	20–40 mg
Lovastatin			40 mg	20 mg
Pitavastatin			2–4 mg	1 mg
Pravastatin			40–80 mg	10–20 mg
Rosuvastatin	20–40 mg		5–10 mg
Simvastatin			20–40 mg	10 mg
Features of Individual Statins
Statin	Dose (mg)	LDL ↓	Comments
Atorvastatin	10–80	38–54%	Generic; preferred in CKD
Rosuvastatin	5–40	52–63%	May be taken at any time; ↑ HDL; ↓ drug–drug interactions; may have ↓ muscle toxicity
Simvastatin	10–80	28–41%	Generic; take in evening; highest drug–drug interactions (incl amlodipine), avoid 80 mg unless already tolerating >1 y 2/2 ↑myopathy risk
Pravastatin	10–80	19–40%	Preferred in liver disease; OK w/ warfarin; ↓ muscle toxicity; generic; ↓ interaction w/ fibrate; take in evening; least drug–drug interactions
Lovastatin	20–80	29–48%	Generic; take in evening
Fluvastatin	20–80	17–33%	Preferred in CKD; ↓ muscle toxicity; OK w/ warfarin
Pitavastatin	1–4	31–41%	May be taken at any time; OK w/ warfarin

Nonstatin lipid-lowering agents: 2013 guidelines do not advocate for addition of any nonstatin drug therapy given lack of evidence they ↓ ASCVD events; more recent evidence suggests addition of ezetimibe to simvastatin may improve CV outcomes (NEJM 2015; 372: 2387–2397); PCSK9 inhibitors (alirocumab, evolocumab) >> LDL reduction than statins, also

 

shown to improve CV outcomes (NEJM 2015;372:1489; 1500)

PCSK9 inhibitors: SC dosing, ↓LDL 61%; evolocumab; 140 mg q2wk, 520 mg q mo, alirocumab; 75–150 mg q2 wk; approved for pts w/FHx and/or ASCVD requiring further LDL lowering; s/e: injection site-reactions, myalgias, ?neurocognitive effects Fish oil (Ω3-acid ethyl esters): 4 g QD or 2 g BID; may ↑LDL, ↓TG 20– 50%; no Δ in HDL

Ezetimibe: 10 mg QD; ↓LDL 17%; can ↑LFTs when used w/statins

Fibrates: ↓LDL ∼10%, ↑HDL 5–20%, ↓TG 40–50%; s/e include

↑gallstones, ↑ risk of rhabdo with statins; gemfibrozil; (600 mg BID): can ↑INR on warfarin, fenofibrate; (145 mg/d nanocrystal, 160–200 mg/d micronized) can → rash, GI upset, myalgia, ↑LFTs,

↑CsA, avoid if CrCl <30

Bile sequestrants: ↓LDL 15–30%; Cholestyramine (2–24 g/d), Colestipol (5–30 g/d): effect additive to statins, take w/ meals; s/e: GI upset, ↓ drug absorption; avoid in biliary/bowel obstruction; effect additive to statins

Hypertriglyceridemia (AFP 2007;75:1365; J Fam Pract 2006;55:S1; NEJM

2007;357:1009)

Screen pts w/ ↑ TG for metabolic synd; blood glucose control key to ↓ TG in diabetics

150–199: Diet (fat <15% total cal, low sugar, ↓ EtOH), exercise (↓ TG up to 25%) 200–499: Consider Rx ↑ risk pts (CAD or equiv); non- HDL chol (TC – HDL) is a 2° target w/ a goal 30 mg/dL higher than LDL goal; statins↓ TG 5–33%

≥500: Ω3-acid ethyl esters (fish oil), fibrate, nicotinic acid to avoid pancreatitis

Patient information: JAMA 2013;309:1419; AFP 2010;81:1103

 

 

HYPERTENSION

Background (JACC 2017 AHA/ACC guidelines; JAMA 2014;311:507; J Clin HTN

2014;16:14)

Classification: Different cutoffs exist for ambulatory (home) readings, but office measurement cutoffs are below

 

Classification of Blood Pressure
	Normal	Elevated (previously pre- HTN)	Stage I HTN (previously pre- HTN)	Stage II HTN (previously stage I and II HTN)
Value (mm Hg)	<120/<80	120–129/<80	SBP 130–139 or DBP 80–89	SBP ≥140 or DBP ≥90
•  To diagnose HTN, BP readings must be elevated on ≥2 visits spaced >1 wk apart unless signs of end-organ damage, hypertensive emergency, or BP ≥ 180/110 mmHg • If SBP and DBP in 2 different categories, use the higher BP category

Epidemiology: According to 2017 guideline definitions, HTN affects 45% of US adults (although pharmacologic treatment is not recommended for many stage 1 patients; per prior guidelines with higher HTN cutoff of ≥140/≥90, affected 31% of US adults, all of whom had pharmacologic tx recommended)

BP control: According to 2017 guidelines, 53% of Americans are above target BP (by JNC 8 guidelines, 39% of Americans are above target BP)

Risk factors: Age, FHx, obesity, African ancestry, renal disease, high sodium diet, DM2, sedentary lifestyle, EtOH

Risks of HTN: Each 20 mmHg ↑ in SBP or 10 mmHg ↑ in DBP over 115/75 mmHg doubles risk of ASCVD-associated death (Lancet

2002;360:1903)

Benefits of lowering BP: 10 mmHg lower SBP → 20% ↓ major cardiac events, 28% ↓ HF, 13% ↓ mortality (Lancet 2016;387:957)

Evaluation (Ann Intern Med 2011;154:781; 2015;162:192; 163:778; NEJM 2003;348:610;

2006;355:385)

Screening (USPSTF): Annually if >40 y or obese or pre-HTN; q3–5 y if 18–39 w/o risk factors

History: Duration of HTN, comorbid conditions (CAD, CKD, stroke, DM, OSA, PAD, thyroid), evidence of end-organ damage, FHx, medication use, lifestyle

Adherence: Ask pts not at goal BP: “Did you take your meds today, at what time? Over the past 2 weeks, how many days did you not take your blood pressure medicine?”

Exam: Cardiac exam (LVH, murmurs, volume status, pulses),

 

fundoscopic, neuro, thyroid, BMI, auscultation for bruits (carotid, renal); average several BP measurements;

BP measurement: Seated, arm supported/level to heart, measured in both arms (JAMA 1995;273:1211); difference in BP measured by auscultation through bell vs. diaphragm of stethoscope is not clinically significant (Blood Press Monit 2016;21:178; J Hypertens 2005;23:499); proper cuff size key: small cuff overestimates SBP by up to 10 mmHg; manual cuffs should be inflated to 200–200 mmHg; high values on automatic cuffs should be confirmed manually; check supine + standing BP in elderly, fall risk, or diabetics to detect/avoid orthostatic HoTN w/ tx (difference in SBP >20 mmHg, HR >20, or sx such as dizziness); check leg BP in young pts w/ ↑ BP (eval for coarctation) Home BP monitors: Should be calibrated in office; pts should keep daily log

Ambulatory (24 h) BP Monitoring (ABPM): For episodic, resistant or white coat HTN; device measures BP q15–60 min while awake/sleeping PseudoHTN: Incorrect ↑ in BP due to stiffened arteries; should be suspected if brachial artery still palpable or may be rolled when cuff inflated 30 mmHg above systolic BP (Osler maneuver) or in pt w/ resistant HTN and no end-organ damage

Initial workup: CBC, electrolytes, LFTs, lipids, TSH, U/A, ECG, HbA1c

Treatment (Ann Int Med 2014;161:ITC1–15; JAMA 2013;310:1274; 2014;311:2216; NEJM

2015;373:2180)

 

Treatment Thresholds and Agents (JNC VIII; JAMA 2014;311:507; AHA/ACC 2017)
	Hx CVD or ASCVD risk >10%	ASCVD risk <10%	Age >65*	CKD	DM	Hx Stroke
Start Rx if BP ≥	130/80	<140/90	SBP 130	130/80	130/80	140/90 (130/80 if lacunar)
Goal BP <	130/80	130/80	SBP 130	130/80	130/80	130/80

*community-dwelling, ambulatory, noninstitutionalized seniors

Lifestyle modification for 3 mo can ↓ SBP by 10 mmHg (NEJM

 

2010;362:2102)

 

Benefit of Lifestyle Modifications (AHA/ACC 2017)
Modification	Average BP reduction	Notes
Weight loss	−5 mmHg	Aim for ideal body weight, est −1 mmHg/ 1 kg lost
DASH Diet	−11 mmHg	Fruits, vegetables, whole grains, and low-fat dairy products w/ ↓ saturated/trans fats (see nhlbi.nih.gov/health/public/heart/hbp/dash/new_dash.pdf)
High K	−4–5 mmHg	3.5–5 g/d, preferably via potassium-rich foods
Low Na	−5–6 mmHg	Reducing intake by at least 1 g/d, goal intake <1.5 g/d
Aerobic exercise	−5–8 mmHg	120–150 min/wk at 65–75% max HR Strength training (dynamic or isometric resistance) also beneficial
Alcohol	−4 mmHg	Reduce intake to ≤2 drinks/d (♂) or ≤1 drink/d (♀)

General principles: 1st-line drugs (ACEI, thiazides, CCB) have equal efficacy (BMJ 2009;338:b1665; JAMA 1993;270:713), except for pts w/ proteinuria (ACEI/ARB to ↓CKD progression, strong recommendation), pts of African ancestry (thiazide or CCB in absence of CKD; some data ACEI/ARB less effective, moderate–weak recommendation); overall degree of CV benefit related to how well BP is controlled; fewer side effects if lower doses of multiple meds (but concern for decreased adherence); mortality benefit to CCB + ACEI > CCB + thiazide

(ACCOMPLISH NEJM 2008;359:2417)

 

Pharmacologic Agents
Agent	Preferred pts	Considerations
ACEI/ARB	CKD; CHF; DM2	Cough w/ ACEI (∼15% pts); ↑ K in CKD; angioedema; avoid in ♀ who are/may become pregnant
CCB	AF African ancestry	Peripheral edema (esp amlodipine); Verapamil/diltiazem: nodal agents & ⊖ inotropes, contraindicated in ↓ EF or heart block; dihydropyridine (ie, amlodipine) preferred for isolated systolic HTN in elderly
Thiazides	Osteoporosis; Kidney stones (↓ renal Ca)	Hypokalemia, most common in 1st wks of tx, prevented by dietary salt

 

African ancestry

restriction; hyperglycemia, esp in DM; hyponatremia; may exacerbate gout & erectile dysfunction; ineffective in pts w/ CrCl <30; can combine with triamterene (Na+ channel antagonist); preferred in elderly with isolated systolic HTN

 

2nd-Line Agents
Drug class	Indications	Notes
αB	BPH, PTSD	Doxazosin, prazosin: ↑ risk of CHF (doxazosin), postural HoTN, nasal congestion; preferred in pheochromocytoma
Aldosterone antagonists	EF<40%	Spironolactone, eplerenone: ↑ K, esp w/ ACEI, DM, CKD; recommended in hyperaldosteronism or refractory HTN; gynecomastia & breast pain (less w/ eplerenone)
βB (JAMA 2013;310:1851)	AF, CAD; Propranolol if migraines, anxiety, ↑ thyroid	Atenolol, carvedilol, metoprolol, propranolol, nadolol, bisoprolol: Angina/rebound HTN on w/ abrupt discontinuation; may mask ↓ glucose in DM; may exacerbate asthma, COPD, impotence; caution in pts w/ conduction disease (heart block), pheo (unopposed α-stimulation); can cause nightmares, fatigue, ↓ exercise tolerance
Clonidine	Anxiety	Available in transdermal weekly dosing to help w/ adherence; anxiolytic; taper to avoid rebound HTN on discontinuation
Hydralazine		TID or preferably QID dosing so difficult med adherence; may cause rebound ↑HR, drug- induced lupus (rare)
Loop diuretics	CHF	Furosemide, bumetanide, torsemide: Useful in refractory HTN w/ CKD (CrCl <30 mmol/min)

Treatment failure: 50–60% of pts w/ HTN will achieve BP control w/ a single agent; 50–80% of pts who fail a 1st agent will achieve BP control by switching to a different agent in a different class, so a sequential single agent approach may be preferable to initial combination Rx (Arch Intern Med 1995;155:1757); may consider switching to a stronger drug within class if applicable; (e.g., not at goal on HCTZ → switch to

 

chlorthalidone, which is a longer-acting and more potent thiazide)

Resistant hypertension: HTN despite 3 drugs (including a diuretic) or 4 drugs dosed at 50% of the maximal dose (JAMA 2014;311:2216); important to r/o medication nonadherence or improper BP cuff size (Hypertension 2016;67:1085); general treatment approach is to r/o secondary causes of HTN (below) or pseudoHTN (above), discontinue any medications that may ↑ BP, check ambulatory BP; initial 3-drug treatment involves an ACEI/ARB + CCB + diuretic (chlorthalidone or furosemide if EGFR <30); if HTN persists then spironolactone may be added as a 4th agent; consider referral to HTN specialist in cases of failure of 4-drug regimens

 

Secondary Causes (JAMA 2014;311:2216)
Cause (% prevalence in resistant HTN)	Notes (Consider if < 30 y, sudden, severe or resistant HTN)
Sleep apnea (60–70%)	“Do you snore, wake up tired, fall asleep during the day?” (see “Obstructive Sleep Apnea”)
Hyperaldosteronism (7– 20%)	↓ K suggestive, but >50% pts normokalemic; ratio of plasma aldosterone:renin >20 off aldosterone antag/ACEI/ARB; confirm w/ saline infusion test; CT for ? adrenal adenomas or bilat adrenal hyperplasia (see “Adrenal Nodules”); Rx w/ aldosterone antagonist
Renal artery stenosis (2– 24%)	Carotid/abdominal bruits; ↑ Cr w/ ACEI/ARB; resistant HTN in young (fibromuscular dysplasia); renal artery U/S, CTA, or MRA
Medications and illicit substances (2–24%)	Antidepressants, NSAIDs, celecoxib, estrogen-OCPs, steroids, decongestants, diet pills, CsA, tacro, herbal meds, ginseng, cocaine, amphetamines
CKD (1–2%)	Proteinuria, elevated Cr, volume overload
Endocrine (1%)	Cushing syndrome, hypercalcemia, hyperthyroidism
White coat HTN	Seen in 10–20% of patients; consider in refractory HTN; ✓ home BP log vs. ambulatory BP monitoring (NEJM 2006;354:2368)
Pheochromocytoma	Palpitations, diaphoresis, pounding HA, episodic HTN; 24-h urine fractionated metanephrines, catecholamines
Aortic coarctation	Discrepancy in BP btw arms/legs, ↓ femoral pulses; abnl CXR

HTN Urgency/Emergency

Urgency: SBP ≥180 or DBP ≥110: May be safely treated in office/home if no significant CV comorbidities, good adherence, and follow-up (JAMA

 

Intern Med. 2016;176:981); ↓ BP to <160/<100 mmHg or by max 25%, then baseline BP in the next hours–days (to avoid cerebral/myocardial/renal ischemia from acute ↓); then standard BP goals

Emergency: HTN urgency + symptoms (chest pain, headache, CVA, papilledema, retinal hemorrhage, AKI): Refer to ED

 

PALPITATIONS AND ARRHYTHMIAS

Background (AFP 2005;71:743)

Definition: Sensation that the heart is beating abnormally; common complaint in ambulatory setting, ∼16% of outpatient visits (Arch Intern Med 1990;150:1685)

Premature ventricular contractions (PVCs): Found in ∼6% of middle-aged pts (Am Heart J 2002;143:535); may manifest as a skipped beat or palpitation

Premature atrial contractions (PACs): Activation of the atria from site other than SA node; may manifest as a skipped beat or palpitation Etiology: 43% cardiac, 31% psychiatric, 10% unknown (Am J Med 1996;100:138); may have >1 etiology (2/3 of pts dx w/ SVT meet criteria for panic d/o) (Arch Intern Med 1997;157:537)

Evaluation (AFP 2011;84:63; JAMA 2009;302:2135)

History: Ask patient to “tap out” rhythm; assoc sx: chest pain/pressure, neck pulsations, syncope/presyncope (most likely CHB or ventricular arrhythmia, rare in SVT), onset, duration, provocative factors (anxiety, exercise, EtOH, caffeine), palliative factors; Has this ever happened before? Review medications, supplements, illicits, EtOH; screen for depression (see “Depression”), anxiety/panic attacks (see “Anxiety & Panic Disorders”)

 

Noncardiac Palpitations (AFP 2005;71:743)
Diagnosis	Clinical Features
Anemia	Fatigue, pica, pallor; see “Anemia”
Depression	Lack of energy, suicidal ideation, disrupted sleep, guilt, inability to concentrate; (see “Depression”)
Dehydration/orthostasis	Assoc w/ standing, ⊕ orthostatic VS

 

Panic/anxiety disorder	Situational triggers (i.e. crowds), paresthesias, fear of losing control/dying, derealization, sweating (see “Anxiety & Panic Disorders”)
Hypoglycemia	Diaphoresis, relieved by eating
Medications/habits	Assoc w/ taking medication or habit (i.e. caffeine)
Thyrotoxicosis	Insomnia, weakness, frequent bowel movements, brittle hair, weight loss; (see “Thyroid Disorders”)
Postural tachycardia syndrome	Chronic fatigue/dizziness/lightheadedness, unexplained spells, inappropriate sinus tachycardia (Mayo Clin Proc 2012;87:1214)
Pheochromocytoma	HA, HTN, orthostasis, weight loss, hyperglycemia
Cardiac Palpitations (NEJM 2006;354:1039; 2012;367:1438)
Diagnosis	Clinical Features
AFib/Aflutter	Older at presentation, “irregular/fluttering” sensation; may present with presyncope, but syncope rare
Atrial tachycardia	Similar to ST but without appropriate stimulus
AV node dependent tachycardia (AVNRT, AVRT)	Younger at presentation, abrupt onset/termination; provoked by exercise; terminates w/ vagal maneuvers (carotid massage, valsalva); AVNRT may be provoked by bending over → standing; may manifest as “pounding in neck” due to AV dissociation
Left or right ventricular outflow tract tachycardia/VT	Younger pts; rapid palpitations w/ dizziness, syncope, provoked by exercise, ↑ catecholamines RVOT may terminate with vagal maneuvers
Premature atrial contraction	“Skipped” beat or “flip-flop” sensation, usually at rest (↑ incidence at ↓ HR)
PVCs	Similar to PACs; more common in pts with CMP, CAD; pt may report flip flopping, pause, or forceful contraction (i.e. after PVC)
Sinus tachycardia (ST)	Gradual onset, regular/fast, assoc w/ exercise/stress
Valvular heart disease	Murmurs heard on exam (see “Vaivular Heart Disease”)
Ventricular tachycardia, nonsustained ventricular tachycardia	More common in high-risk pts (CMP, CAD) & older pts; rapid palpitations w/ dizziness, presyncope, syncope; can be postexertion (long QT)

Exam: Heart sounds for signs of structural/valvular heart disease; assess JVP, edema, and pulmonary exam for CHF; mid-systolic click associated w/ mitral valve prolapse

Workup: Electrolytes + Mg, ECG; otherwise directed by sx; consider

 

CBC (evaluate anemia), TSH (thyrotoxicosis), serum/urine catecholamines/metanephrines (pheochromocytoma), fingerstick

ECG: Baseline rarely documents culprit arrhythmia, but should be obtained on all pts with palpitations since can help w/ diagnosis of ischemic heart disease (see table below) Continuous (Holter) monitoring: 24–48 h or 7–14 d for Zio patch; best for pts with frequent sx or sx w/ activity; requires pts to keep log of symptoms/activities for best interpretation; 48–96 h monitors available, as well (Circulation 1999;100:886) Event monitor/loop recorder: Intermittent or continuous recording; pt can activate during sx; good for those with infrequent episodes Implantable loop recorders: Best for those w/ particularly infrequent episodes; can stay in place for up to 36 months Exercise treadmill test: Useful for provoking arrhythmias that occur during exercise, including SVT and the idiopathic outflow tract tachycardias EP testing (referral): Consider in pts w/ palpitations → syncope or serious sx, in pts who have known structural heart dz, or who are at risk for structural heart dz (Circulation 1995;92:673)

Risk stratification: (NEJM 1998;338:1369)

High-risk: ⊕ FHx of SCD, AF, CAD, arrhythmia; personal hx HTN, syncope or presyncope, valvular heart dz, CAD, CMP, HOCM, recurrent sx → ambulatory ECG monitoring; if ambulatory ECG (–) but arrhythmia still suspected → EP referral Low-risk: No evidence of structural heart disease/arrhythmia; H&P + ECG is sufficient

 

Resting ECG Findings and Potential Etiology (Adapted from NEJM 1998;338:1369)
ECG Finding	Etiology
Short PR, delta wave	Wolff–Parkinson White, AVRT
Long QT (often + bradycardia)	Polymorphic VT
Q waves (prior MI)	PVCs, NSVT, VT
Q waves in I, aVL, V4–V6 + LVH	Hypertrophic cardiomyopathy
P mitrale, LVH, PACs	Large L atrium → atrial fibrillation
PVCs with LBBB morphology & + axis	Right ventricular outflow tract tachycardia
PVCs with RBBB morphology & (–) axis	Left ventricular outflow tract tachycardia

 

Mobitz II		Complete heart block
Inverted T wave in V2, +/-epsilon wave		Arrhythmogenic right ventricular dysplasia
Identification of Tachycardia
QRS	Regular	Regularly Irregular	Irregularly Irregular
Narrow	Sinus rhythm Atrial tach Atrial flutter AVNRT/AVRT	Mobitz I Mobitz II Bi-/tri-geminy	Sick sinus Atrial fibrillation Multifocal atrial tach/wandering atrial pacemaker
		Regular rhythm w/ variable AV conduction
Wide	Above rhythms w/ aberrant conduction (baseline IVCD or BBB)
	Ventricular tach WPW Ventricular pacing		PVC Torsades/polymorphic VT VF

Management  (AFP 2011;84:63)

ER referral: (1) Syncope/near syncope with high-grade AV block; (2) Syncope in pts w/ known or high risk for cardiac disease (i.e., positive FHx for SCD); (3) Concern for VT; (4) Afib w/ slow or rapid ventricular response; (4) Symptomatic bradycardia Electrophysiology/cardiology referral: (1) Sustained or poorly tolerated palpitations; (2) High likelihood of structural heart disease in an otherwise stable pt; (3) Persistent SVT or PVCs not managed with β-blockers; (4) Unclear dx

PVCs or SVT: Some studies observed assoc w/ ↑ mortality, even for pts w/o heart disease (Heart 2012;98:1290); however, ↓ PVCs in pts w/o heart disease not shown to ↓ mortality (JACC 2006;48:e247); consider βB and eval for structural heart disease (i.e., TTE and/or stress test) if risk factors present; if sx persist despite βB or assoc w/ syncope, consider cards referral for antiarrhythmic Rx or EP evaluation (NEJM 2006;354:1039) PACs: Reassurance; discontinue triggers (i.e., caffeine, nicotine, EtOH, avoid stress); consider β-blockers for persistent symptoms

 

Atrial Fibrillation and Flutter

Background (Ann Int Med 2008;149:ITC5–2; 2017;ITC-34; Circulation 2014;130:2071;

 

2015;131:1648; JAMA 2001;285:2370; Mayo Clin Proc 2013;88:394)

Paroxysmal: <1 wk, terminates spontaneously or with Rx; persistent:

>1 wk, can be terminated w/ cardioversion; long-standing persistent:

(>1 y); permanent: (no sinus rhythm)

Valvular: 2° to valve dz (MR, MS, MVP, valve replacement/repair) vs.

nonvalvular

Secondary causes: Pericarditis, myocarditis, thyrotoxicosis, COPD, obesity, OSA, pheocromocytoma, cardiac surgery, MI, PE, CHF, PNA, EtOH (“holiday heart”), caffeine (69% of pts have no precipitant identified)

Prevalence: ↑ w/ age, underlying heart disease, men, Caucasians; 0.1% of adults age <55, 9% of adults >80; overall US prevalence ∼1% adults

Pathophysiology: Atrial fibrosis and loss of atrial muscle mass → nonhomogeneous wave propagation → creates multiple wavelets and focal automaticity (often originating in the pulm veins) → anatomical and electrical remodeling

Risk factors: ↑ atrial pressure (valvular disease, CHF, MI, cor pulmonale, PFO, COPD, CMP, HTN w/ LVH), ↑ atrial size (obesity, AFlutter), SVT, atrial ischemia (CAD), atrial fibrosis/infiltrate (age, amyloid, atrial neoplasm), neuro (SAH, CVA), genetics (family hx, European ancestry), EtOH abuse

Evaluation (Circulation 2006;114:e257; NEJM 2004;351:2408)

Symptoms: Asymptomatic (esp elderly, recurrent AF), SOB, DOE, fatigue, ↑ urination, lightheadedness (syncope rare), angina, palpitations, CVA, CHF; symptoms more prominent w/ paroxysmal, less evident w/ persistent and permanent

Exam: Irregularly irregular pulse, tachycardia, irregular heart sounds, ± HoTN

Workup: H&P (focused on classification criteria above, and signs of reversible causes), ECG (LVH, prior MI, bundle branch block, WPW which changes management options), CXR (cardiomegaly, pulm pathology), TTE (for new-onset AF); TSH and free T4 (hyperthyroidism), electrolytes, renal and LFTs function (to eval risk of toxicity w/ specific therapies); FOBT (prior to starting anticoag); eval for MI not necessary unless ischemic sx; ✓HR at rest and w/ exertion (i.e.,

 

walking) in pts w/ sx related to exertion; 12-lead ECG, 24–48 h Holter, loop recorder (if sx)

ECG DDx: AT, sinus tach w/ premature atrial beats, MAT, AFlutter, SR w/ frequent PACs; AF should have no discernible P-waves, no pattern in ventricular response

Additional testing to consider: Holter or 6-min walk test (eval rate control), TEE (if cardioversion planned), EP study (if AF due to SVT, WPW, ablation planned)

Indications for hospitalization: Hemodynamic instability, elderly, associated medical problem (i.e., 2° cause of AF), DCCV, initiation of antiarrhythmic therapy or heparin

Indications for cardiology referral: Failure of rate control, complex cardiac disease, candidates for PPM, defibrillator, ablation, or surgery

(AFP 2011;83:61)

Rate Control (Circulation 2010;123:104; JAMA 2015;314:278; NEJM 2002;347:1825;

2002;347:1834; 2008;358:2667)

Preferred initial approach in most patients, including those with CHF; no significant difference in survival or CVA w/ rate vs. rhythm control; aim is to prevent symptoms, hemodynamic instability, and tachycardia- mediated cardiomyopathy

Therapeutic goal: Lenient rate control (rest HR <110) as effective as strict rate control (rest HR <80, moderate exercise HR <110) in pts w/ persistent AF, well-controlled sx and an LVEF >40% (NEJM 2010;362:1363)

 

Pharmacologic Therapy (Ann Int Med 2008;149:ITC5–2; Circulation 2006;114:e257)
	Agent	Maintenance (PO)	Comments
βB	Atenolol Carvedilol Metoprolol Propranolol	25–100 mg QD 3.125–25mg BID 25–100 mg BID/TID 80–320 mg/d (total)	Preferred in CAD, CHF. Caution w/ COPD, asthma. Contraindicated in WPW. Use cautiously in decompensated CHF. Propranolol w/ minimal BP effect. Atenolol does not cross BBB.
CCB	Diltiazem Verapamil	120–360 mg QD divided doses 120–360 mg QD divided doses	Preferred in COPD/asthma; caution in CHF w/ decreased EF due to negative ionotropy; ↓ HR & BP through myocardial suppression. ↑ digoxin levels. Contraindicated in WPW.

 

Digoxin

0.125–0.5 mg QD

Useful in CHF/sedentary pts. Controls only resting HR (no effect on adrenergic tone). Adjust for CrCl. Avoid in paroxysmal AF, WPW. May cause heart block, ↓ HR. Levels correlate poorly w/ rate; >2 ng/mL toxic. Caution in elderly.

βB are the most effective agent for rate control; if single agent ineffective consider switching to a different class or using a combination (JACC 2004;43:1201); digoxin may be used as 2nd agent because of additive effect to βB or CCB on HR

Rhythm Control (Circulation 2010;123:104)

Therapeutic goal: Pursue rhythm control if AF symptomatic, rate control has failed, or if there is reasonable chance for prolonged SR (structurally normal heart); rhythm control associated with ↑ adverse drug effects and ↑ hospitalizations compared to rate control; hospitalization may be required for telemetry during initiation of some agents; TTE or stress test may be needed to select agent; refer to cardiology/EP for rhythm control

 

Common Medications Used to Maintain NSR (Cardiology Consultation Advised)
Drug (Class)	Dose (PO)	Adverse Effects and Comments
Amiodarone (III) (Arch Intern Med 2000; 160:1741; JAMA 2008;300:1784; NEJM 2005;352:1861; 2007;356:935)	200–400 mg QD (Load: 600–800 mg in divided doses QD up to 10 g total)	Most effective at maintaining NSR and least proarrhythmic but most long-term side effects: Pulmonary/thyroid/hepatotoxicity, neuropathy, skin photosensitivity, ↓ HR, optic neuritis, torsades, ↑ QTc; episodic Rx after cardioversion ↑ mortality and AF recurrence; ✓ TFTs, LFTs q6mo, baseline PFTs, CXR & ECG q12mo; ↓ warfarin/digoxin metabolism, follow INR/digoxin level closely; preferred for CHF, CAD, HTN w/ LVH; outpt initiation in select patients; anticoagulate prior to Rx due to CVA risk w/ conversion to NSR
Dofetilide (III)	0.5 mg BID	Torsades, ↑ QTc; dose adjustment in renal insufficiency; monitor K; preferred for CHF, CAD; initiation

 

		requires hospitalization for 72 h
Dronedarone (III)	400 mg BID	↓ HR & SBP, ↑ QTc, rare hepatotoxicity. ↑ mortality in symptomatic or severe HF (EF <35%); ↑ CVA, MI, systemic embolism, or CV mortality in pts w/ permanent AF and h/o CAD, CVA/TIA, symptomatic CHF, PAD, EF <40%, or ≥75 y w/ HTN & DM; better tolerated than amiodarone but ↓ effective; ✓ LFTs first 6 mo. May be initiated outpt. ↑ digoxin levels; no warfarin interaction
(J Cardiovasc Electrophys
2010;21:597; NEJM
2007;357:987; 2008;358:2678;
2009;360:668; 2011;365:2268)
Flecainide (IC)	200–300 mg	VT, CHF, AFlutter. Avoid in pts with CAD or structural heart disease; pretreat w/ βB or CCB to prevent AFlutter
Sotalol (III)	80–160 mg BID	Torsades, CHF, ↑ QTc, bradycardia, COPD exacerbation; adjust dose in renal insufficiency; ✓ K, QTc; used in CAD; initiation requires hospitalization

Counseling: Recurrence not indicative of failure; patients may have fewer and shorter episodes; rhythm control associated w/ arrhythmia → warn pts about significance of syncope/palpitations Nonpharmacologic Tx: Alternative in symptomatic patients who have failed antiarrhythmic tx

Radiofrequency ablation: AV node ablation + PPM if pharmacologic Rx inadequate (NEJM 2001;344:1043; 2002;346:2062); ∼80% success; requires uninterrupted anticoagulation (NEJM 2012;367:1587; JAMA 2014;311:692) Surgical “maze” procedure: 70–95% success if undergoing cardiac surgery

Cardioversion (Ann Intern Med 2003;139:1018; NEJM 2001;344:1411)

When: First episode or symptomatic AF (causing CHF exacerbation, angina, HoTN); address reversible causes of AF prior to cardioversion; pts w/ new-onset AF do not need maintenance antiarrhythmic therapy after cardioversion (Ann Intern Med 2003;139:1009)

How: Pharmacologic is less likely to be successful than DCCV; “Pill in Pocket”: Flecainide or propafenone safe as outpt if previously proven safe in hospital, pt w/o CAD, structural or conduction system disease,

 

prolonged QT (NEJM 2004;351:2384); consider βB or CCB to prevent rapid AV conduction w/ Aflutter

Anticoagulation: Risk of embolization identical for spontaneous, pharmacologic, or electrical cardioversion; if AF >48 h or ? duration or

<48 h w/ mitral stenosis or h/o thromboembolism → 3–5% risk of CVA; therefore, anticoagulate all patients for DCCV; Anticoagulate: >3 wk prior to cardioversion and ≥4 wk postcardioversion (due to atrial stunning), regardless of CHA₂DS₂-VASc score

TEE: Consider if patient hospitalized, at risk for bleeding from prolonged anticoagulation, or unlikely to tolerate prolonged AF; if TEE negative for thrombus, cardioversion may be performed with heparin → warfarin bridge or dabigatran (4 wk Rx)

Factors affecting success: Time in AF (better if AF <1 wk), LA size, age, pretreatment w/ antiarrhythmic (class IC or III) especially if prior DC cardioversion failed

ANTICOAGULATION (Circulation 2014;130:2071; JAMA 2015;313:1950)

 

Risk stratification: CHA₂DS₂-VASc most validated and clinically useful score for long-term anticoagulation in paroxysmal, chronic AF, and s/p cardioversion (JACC 2008;51:810)

Other risk factors (less validated): Age 65–74, female sex, CAD

Risk–benefit: Benefits of anticoagulation weighed vs. pt hx (i.e., GIB, falls, ICH, ↓ PLT, nonadherence, substance/EtOH abuse, psychiatric history, heavy NSAID use, liver disease, pregnancy); prognostic scores for bleeding risk available (Am J Med 2013;126:105); generally, anticoagulation ↑ risk of intracranial hemorrhage by ∼2x to 0.3–0.8%/y compared to pts who are not anticoagulated (Am J Med 2013;126:105); benefit of anticoagulation >> risk of bleeding at other, extracranial sites or from falls; risk–benefit analysis: www.sparctool.com

 

CHA2DS2-VASc Scoring for Stroke Risk (Circulation 2014;130:2071)

CHA2DS2-VASc: CHF (1 point), HTN (1), Age 65–74 (1); DM (1), hx Stroke/TIA (2), Vascular disease (prior MI, PAD, aortic plaque) (1), Age ≥75 (2), Sex, if female, (1)

 

CHA2DS2-VASc score 0 → Consider ASA (81–325 mg); 1 → ASA, warfarin, or direct oral anticoagulant (DOAC) based on pt preference & shared decision-making; ≥2 → Warfarin or DOAC; Pts w/ low initial score should be continually reassessed for anticoagulation

INR Goals (Blood 2012;119:3016)

Nonvalvular AF: 2–3; Valvular AF: Native valve, goal INR 2–3; prosthetic valve, goal INR 2.5–3.5; newer anticoagulants not eval for valvular AF

Valvular AFib: All valvular AF (i.e., rheum MS, valve prosthesis or repair, severe valvular disease) should be anticoagulated as stroke risk very high; DOACs not yet studied

Nonvalvular AF: Unless a reversible cause for AF is corrected, AF → long-term anticoagulation (even if in SR) regardless of AF classification (paroxysmal vs. persistent) or treatment (rate vs. rhythm) because CVA risk no different (Circulation 2015;131:1648); average CVA risk w/o anticoagulation ≈5%/y vs. 1.4% with warfarin; AF → 15% of CVA in US

(JAMA 2002;288:2441; 2003;290:2182; 2003;290:2685)

Warfarin: Only 60% of pts at goal INR in “usual” clinical practice (NEJM 2011;365:952); warfarin ↓ CVA risk by 68% vs. 21% for ASA but ↑ bleeding; most pts do not need LMWH bridge while awaiting therapeutic INR; consider LMWH bridge in pts at ↓ risk of bleeding, & h/o TIA/CVA or intracardiac thrombus

Use w/ antiplatelet agents: For pts on warfarin (i.e., AF w/ stent) ASA 81 mg QD and/or clopidogrel 75 mg QD may be used; aim for INR 2.0–2.5 due to ↑ bleeding Comparison w/ newer agents: Rivaroxaban/dabigatran: Fixed dose, rapid onset, ↓ drug & no food interactions, no monitoring, & no antidote (Am J Med 2013;126:105)

ASA w/ clopidogrel: Inferior to warfarin for stroke prevention (Lancet 2006;367:1903). Superior to ASA alone but with higher bleeding risk (NEJM 2009;360:2066); acceptable if pt/physician preference against warfarin or if pt unsuitable for warfarin

Periprocedural: Patients at low risk for thromboembolism (i.e., no mechanical valves, h/o thromboembolism, low EF, or mitral stenosis) do not need a heparin bridge during periprocedural discontinuation of anticoagulation if interruption is <7 d; consider bridging if high CHA2DS2-VASc (NEJM 2015;373:823)

 

Direct Oral Anticoagulants (DOAC) for Nonvalvular AF

 

Agent	Dosing	Efficacy & Safety vs. Warfarin
Dabigatran (Direct thrombin inhibitor)	150 mg BID (75 mg BID if CrCl 15–30)	↓ ischemic stroke & ICH; no ↑ in major bleeding (NEJM 2009;361:1139) Risks: GI side effects
Rivaroxaban (FXa inhib)	20 mg QD (15 mg QD if CrCl 15–50) w/ pm meal	≈ischemic stroke (NEJM 2011;365:883)
Apixaban (FXa inhib)	5 mg BID (2.5 mg BID if ≥2 of: ≥80 y, ≤60 kg, Cr ≥1.5 mg/dL)	≈ischemic stroke, ↓ mortality. (NEJM 2011;365:981)
Edoxaban (Fxa inhib)	60 mg QD if CrCl 51–95 (30 mg if CrCl 15–50)	60/30 mg: ≈ischemic stroke & ↓ major bleed incl ICH, 14% ↓ CV death (NEJM 2013; 369: 2093)
Caution with med interactions (ketoconazole, clarithromycin, rifampin, phenytoin); onset w/in hours; 1 missed dose may ↓ protection; dabigatran reversed w/ idarucizumab (NEJM 2015;373:511)

Nonpharmacologic therapy: Percutaneous LAA occlusion device (noninferior to warfarin (Lancet 2009;374:534)),but not yet FDA approved; surgical LAA amputation

Patient handout: AFP 2011;83:71; JAMA 2010;303:380;

2015;313:1070

ATRIAL FLUTTER

 

Evaluation

Definition: Reentrant atrial rhythm (typical cycle at rate of 300/min)

History: Similar to AFib

Risk factors: CHF, COPD, obesity, thyroid disease, mitral valve prolapsed, rheumatic heart disease

Evaluation: ECG (typically 2:1 conduction, absent P-waves, saw- toothed flutter waves, atrial rate ∼300 BPM), TTE; ✓CBC, Chem-12, TSH; CXR or ETT if indicated

Treatment

Cardioversion: Spontaneous, electrical, pharmacologic,

 

radiofrequency-ablation, or pacemaker-based; useful if pt symptomatic or if rate poorly controlled/tolerated

Rhythm control: Many of the same drugs used to maintain NSR in AF used in flutter

Rate control: CCB (verapamil or diltiazem)—use w/ caution in pts w/ sick sinus syndrome, AV block, and CHF; βB and digoxin also useful Anticoagulation: Managed in same way as pts w/ AF, including pericardioversion

 

SYNCOPE AND ORTHOSTASIS

Background (Eur Heart J 2009;30:2631; Heart Rhythm 2017:S1547; NEJM 2000;343:1856; 2002;347:878)

Definition: Abrupt, brief, total LOC & postural tone w/ spontaneous recovery Presyncope: Prodrome to LOC; Reflex/neurocardiogenic syncope “fainting:” Includes vasovagal, situational syncope (i.e., in relation to blood draw, micturition, or cough) & carotid hypersensitivity; neurally mediated vasodilatation/bradycardia → HoTN Epidemiology: 1–3% of ER visits, 11–33% lifetime risk, ↑ w/ age; orthostatic HoTN found in up to 20% pts >65 y w/ incidence ↑ w/ age

(Am J Med 2007;120:975)

Etiology: Unexplained (34–39%), vasovagal (14–21%), cardiac (10–

18%), orthostatic (10%), neurologic (7–10%), situational (3–5%),

medications (3%), psychiatric (1–2%), carotid hypersensitivity (1%) (Ann Intern Med 1997;126:989; Med Clin North Am 2001;85:423)

Pathogenesis: ↓ perfusion to cerebral cortex or reticular activating

system → LOC

DDx: Cardiovascular: Valvular heart disease (i.e., AS), PE, CAD, pHTN, subclavian steal, aortic dissection, cardiomyopathy, arrhythmia, tamponade, PPM failure; Neurologic: TIA/CVA, seizure, atypical migraine, SAH, cataplexy, drop attacks; Other: Falls, hemorrhage (GIB, ruptured aortic aneurysm, spleen, ectopic pregnancy), orthostasis/vasovagal, hypoglycemia, psychiatric, anaphylaxis, meds, EtOH, illicit, hyperventilation/hypocapnia, postexercise hypotension

Evaluation (AFP 2011;84:640; Ann Intern Med 2011;155:543; Circulation 2006;113:316;

 

NEJM 2013;369:966)

H&P: Does episode meet definition of syncope? Happened before and how often? What was pt doing prior? Does pt remember hitting ground? Associated sx: Chest pain, dyspnea, palpitations, prodrome, postictal state; provocative factors (exertion, changing position, eating, coughing, sneezing, swallowing, anxiety, pain, defecation/micturition); collateral historians; medication Δs; family hx of cardiac disease, SCD

 

Clues for Syncope in the Patient History (Eur Heart J 2009;30:2631; JACC 2002;40:142)

Reflex: Nausea, warmth, diaphoresis, pallor, lightheaded, fear, pain, emotional distress, instrumentation (i.e., blood draw), or prolonged (>20 min) standing Seizure: Aura, injury, tongue biting, incontinence, postictal state, seizure activity Arrhythmia: Palpitations; syncope while sitting or supine; usually sudden & unheralded Orthostatic HoTN: ↓ volume (diarrhea, GIB, vomiting, fever), dysautonomia (DM, amyloid, Parkinson’s, Shy-Drager, EtOH, prolonged bedrest), adrenal insuff, postural tachycardia syndrome (POTS); may present as fatigue/cognitive impairment in elderly Drugs: Medication changes or new medications? Vasoactive (α-and β-blockers, CCB, nitrates, antiHTN), diuretics, digoxin, EtOH, antidepressants, sedatives, erectile dysfunction medications, insulin. Antiemetics, antiarrhythmics, or antipsychotics (↑ QT)

Exam/Workup: Orthostatic BP, cardiac, pulmonary, neuro exams; survey body for trauma; ✓ tongue for injury; ✓ carotid bruits; ✓ volume status (JVP, mucous membranes, skin tenting); murmur concerning for aortic stenosis; consider rectal exam & guaiac if GIB suspected; ✓ UE vs. LE BP and pulse if subclavian steal suspected

Orthostasis: ↓ SBP by ≥20 mmHg or ↑ HR ≥20 bpm from supine to standing; standing → pooling of 0.5–1 L blood in LE/splanchnic circulation; BP should be measured at 2 and 5 min after position change Carotid massage: Consider in pts >40 y (avoid in pts w/ h/o carotid stenosis/bruits, severe arrhythmia, acute MI or TIA/CVA); Unilateral pressure to angle of jaw for 5–10 s; ⊕ test: ↓ SBP ≥50 mmHg (vasodepressor), asystole ≥3 s (cardioinhibitory), or both (mixed); perform in monitored setting w/ IV access (JAMA 2004;292:1221)

 

Potential Studies to Obtain in Syncope and Diagnostic Yield
Study	Yield	Patient Population (Med Clin North Am 2001;85:423)
H&P	45%	General pts w/syncope

 

ECG w/ rhythm strip	5%	General pts w/syncope
TTE	5–10%	Known or suspected heart disease
ETT	1%	Suspected CAD or exertional syncope. Perform after TTE
Holter	19%	Heart dz, suspicion for arrhythmia, abnormal ECG
Event recorder	34%	Frequent syncope, suspicion for arrhythmia, neg cardiac w/u
Implanted recorder	59%	Negative cardiac w/u & tilt table, infrequent syncope
EP studies	60%	Heart disease & suspicion for arrhythmia
EEG	1–2%	Witnessed seizure, h/o seizure, postictal state
Head CT	4%	Focal neuro deficits, seizure, head trauma, suspected TIA
Tilt testing	49%	Unexplained syncope, workup otherwise negative
Labs (based on history)		INR if on warfarin, UA/UCx if elderly, hCG, CBC, Chem-12, B12, am cortisol, syphilis, HIV, A1c, BNP, 24-h urine Na • Labs: INR if on warfarin, UA/UCx if elderly, hCG, CBC, Chem 12, consider B12, AM cortisol, syphilis, A1c, HIV, BNP, 24-h urine Na depending on clinical scenario

ECG findings: Bradycardia, tachycardia (usually associated w/ palpitations), afib/flutter, VT, AV or bundle branch blocks, abnormal PR, QT, or QRS intervals, pauses, Brugada syndrome (RBBB + STE in V₁–V₃), Q-waves, low voltage, WPW (short PR + upsloping QRS). Δ

from prior ECGs. PE: Right heart strain, S1, QIII, TWI in III Tilt table testing: Used to differentiate reflex syncope vs. orthostatic HoTN; exclude arrhythmias first in pts w/ heart dz TTE: Only if valvular or structural disease suspected by H&P or ECG

Cardiac monitor: If high arrhythmia suspicion; type determined by frequency of episodes: Holter (24–72 h), event or loop monitor (2–6 wk), external patch (2–14 d), implantable loop recorder (ILR) (2–3 y)

Management (AFP 2011;84:527; NEJM 2005;352:1004; 2008;358:615)

Red flags to consider hospitalization or intensive workup: Known or suspected heart dz (i.e., CAD, CHF, AS); abnormal ECG (see

 

above); severe lab abnormalities; FHx of SCD; syncope w/ exertion or when supine; syncope w/ palpitations, headache, chest pain, neurologic deficits, or dyspnea; older age & multiple comorbidities; abnormal physical exam; injury; absence of prodrome; new-onset seizures (AFP 2005;72:1492; 2011;84:640; Ann Intern Med 1997;127:76; NEJM

2000;343:1856)

Reassurance: Pts w/ single reflex syncopal episode, normal ECG, no red flags

Orthostatic HoTN: Hydration (2–2.5 L/d) & drink water rapidly (0.5 L in 5–15 min → up to 20 mmHg ↑ SBP that lasts 1–2 h), stand slowly & in stages, avoid hot weather, sleep w/ HOB at 10–20° (useful in supine HTN), compression hosiery, exercise, tense legs while standing; respiratory measures & handgrips (Lancet 1992;339:897; Neurology 2007;69:582); if HoTN is postprandial, pts should avoid EtOH & large or carbohydrate- rich meals, and not stand or do vigorous activities after eating (NEJM 1983;309:81). D/c precipitating meds & use short-acting antiHTN Rx (i.e., nitropaste) qhs when supine (Lancet Neurol 2008;7:451)

Fludrocortisone: ↑ fluid retention and blood volume; titrate dose in

0.1 mg increments each week; pts should keep log w/ orthostatic BPs; check supine BPs for HTN, monitor for edema & hypokalemia, avoid in ESRD, CHF (Lancet Neurol 2008;7:451); low-dose NSAIDs may augment effect Midodrine: α1-agonist; monitor for supine HTN; pts should keep log w/ orthostatic BPs; monitor for anxiety, GI upset, urinary retention, tachyphylaxis, avoid in CAD; combination w/ fludrocortisone → synergistic effect (JAMA 1997;277:1046) Dietary Na/salt tabs: Up to 10 g/d, esp if 24-h urine Na <170 mmol (goal = 150–200).

Preventing recurrent vasovagal syncope: Physical counterpressure (cross legs and tense, abdominal, & gluteal muscles, grip one hand with another & pull away, leg pumps, squeeze objects w/ hands), avoid triggers, lie down w/ legs elevated when sx occur (JACC 2006;48:1652); role of support stockings, abdominal binders, liberalized fluid/salt intake, midodrine, and fludrocortisone unclear, but may be considered on case basis; paroxetine found in a small RCT to ↓ recurrent syncope (JACC 1999;33:1227).

Driving: Document pt was counseled; DMV reporting requirements vary by state

 

Driving Restrictions in Syncope
Diagnosis	Private Drivers	Commercial Drivers
Unexplained syncope (single episode)	No restriction unless absence of prodrome, occurrence during driving, or heart disease	Determined after diagnosis and treatment established
Single reflex syncopal episode	No restrictions	No restriction unless during high risk activity
Recurrent/severe reflex syncope (i.e., no prodrome, syncope during driving, no provocative factors)	Until symptoms controlled	Permanent restriction unless effective treatment established

Adapted from Circulation 1996;94:1147; Eur Heart J 2009;30:2631

Prognosis: Cardiogenic syncope associated w/ 2-fold ↑ CV and all- cause mortality, up to 10% in 6 m and 50% in 5 y; no increased risk of CV or all-cause mortality w/ vasovagal syncope (NEJM 2002;347:878).

Patient information: JAMA 2004;292:1260

 

HEART FAILURE

Background (Circulation 2013;128:1810; JACC 2009;53:e1; J Card Failure 2010;16:475;

NEJM 2003;348:2007)

Definitions: Heart failure (HF) is a clinical syndrome of dyspnea, fatigue, & fluid retention; due to inability of the heart to pump sufficient blood to meet the body’s metabolic needs

Asymptomatic LV dysfunction: EF ≤40% noted on imaging done for other reasons (i.e., post-MI, revascularization); no prior hx clinical HF sx; progresses to sx HF ∼10%/y HF w/ reduced ejection fraction (HFrEF, systolic HF): Sx of HF & low EF (≤40%); Causes: CAD, valvular disease, HTN, PE, HIV, peripartum cardiomyopathy (CMP), cardiotoxic agents (doxorubicin), EtOH/substance abuse, infiltrative disease, connective tissue dz, thyroid disease, myocarditis, chronic tachycardia; varying degrees of LV enlargement may accompany HFrEF

HF w/ preserved EF (HFpEF, diastolic HF): Normal EF (≥50%) w/

 

sx of HF; half of all HF pts; most are elderly, ♀, & have HTN; ↓ diastolic relaxation, ↓ ventricular filling most commonly due to HTN, ischemia, or restrictive/infiltrative CMP; asx diastolic dysfunction assoc w/ progression to diastolic HF (Ann Int Med 2013;158:ITC5–1; JAMA 2003;289:194; 2011;306:856; NEJM 2017;376:897); other

causes include valvular/pericardial/congenital disease (Lancet 2003;362:777; NEJM 2008;359:2456); survival similar to slightly better than HF w/ ↓ EF (NEJM 2006;355:260) HFpEF, borderline: EF 41–49%,

with clinical characteristic & treatment patterns ∼ HFpEF

High-output HF: Syndrome of HF sx, ↑ CO & ↓ SVR, normal or ↑EF, due to AV fistula, pregnancy, hyperthyroidism, anemia, liver/renal dz, Paget, Beriberi, VSD

Epidemiology: 5.1 million adults in US, ∼2.2% prevalence which ↑ w/ age; accounts for >1 million hospitalizations annually (Circulation 2010;121:e46; JAMA 2003;289:194)

Risk factors: HTN, DM, metabolic syndrome, atherosclerotic coronary disease, EtOH, smoking, obesity (NEJM 2002;347:305), prior chest radiation, rheumatic fever, vitamin deficiencies, ↑ risk if parents had HF (NEJM

2006;355:138)

Evaluation (AFP 2004;70:2145; 2006;74:1893)

 

History                                                  Exam
First presentation with HF Referral to cardiologist for complete initial evaluation	Dyspnea, fatigue, PND (“Do you wake up at night short of breath, coughing, or choking?”), orthopnea (dyspnea lying flat), ↑ wt, weakness, edema, palpitations, CP, ↓ exercise tolerance/functional level; duration of sx Risk factors (above), depression, FHx; hx substance use, esp EtOH, cocaine, chemotherapy, alt medicines	✓  BMI, orthostatics Lung crackles (not always present), S3 and/or S4, displaced apical impulse, LV/RV heave, JVP Peripheral edema, ascites Pulsus alternans, peripheral vasoconstriction Signs of CAD/PAD (peripheral pulses, carotid bruits)
Subsequent visits (routine)	Dyspnea, fatigue, PND, orthopnea, edema, palpitations, CP, ?exercise tolerance, functional level Patient- reported outcome measures (PROMs),a ?depression Review log of daily wt, diet & med & exercise regimen adherence	Establish & document dry wt JVP, lung/cardiac exam as above

 

	Can pt afford meds + healthy food?
Subsequent visits (new/worse symptoms)	Change in symptoms Review log of daily wt, diet, & med adherence Exacerbation triggers: Infection, medication/diet adherence, arrhythmia (esp AF), anemia, EtOH, renal dysfunction, ischemia	Orthostatics Signs volume overload: Lung crackles, S3 +/– S4, JVP, edema, ascites Signs low cardiac output: tachycardia, pulsus alternans peripheral vasoconstriction

aPROMs: Detailed symptom questionnaires to better evaluate and track symptoms; lower scores assoc w/ HF hospitalizations, death; Kansas City Cardiomyopathy Questionnaire (KCCQ), Rose Dyspnea Scale (RDS), Minnesota Living w/ Heart Failure (MLHFQ), PHS2 (Patient Health Questionnaire)

 

Labs                                      Studies
First presentation with HF	CBC, electrolytes, BUN/Cr, Ca, Mg, A1c, BNP/NTproBNP,a LFTs (↑ in hepatic congestion), lipids, TSH, UA; if anemic ✓ iron studies, B12, folic acid	ECG, TTE, CXR (r/o pulmonary causes of dyspnea) Consider based on pt hx, usually by cardiologist: cath, stress test, sleep study, 6-min walk test, ✓ HIV, iron/ferritin, ACE level, SPEP, serum free light chains, ANA, dsDNA, urine metanephrines, selenium/thiamine level, Chagas, Lyme, carnitine, α-galactosidase
Subsequent visits (routine)	Electrolytes, BUN, Cr when titrating meds Establish BNP/NTproBNP at dry weight	ECG TTE per guidelines for follow-up of moderate/severe valve dz, or to reassess EF after MI, if candidate for ICD/CRT
Subsequent visits (new/worse symptoms)	Electrolytes, BUN, Cr BNP/NTproBNP	ECG TTE usually NOT helpful, unless concern for worsening valvular dz/missed MI

aBNP: ProBNP released by ventricles → cleaved to BNP (active) & NTproBNP (inactive); useful along w/ other factors in diagnosing CHF as cause of dyspnea in emergency & primary care settings (J Am Coll Cardiol 2003;42:1793; NEJM 2002;347:161); Nl values ↑ w/ age; falsely low in obesity; ↑ trend assoc w/ worse prognosis (BMJ 2005;330:625); target value to guide tx remains controversial (Circulation 2013;127:500; 509)

Classification (NEJM 2010;362:228; 1992;327:685; 1991;325:293; 1987;316:1429)

NYHA class used to guide therapy and determine treatment options

 

NYHA/AHA Heart Failure Classification
New York Heart Association		ACC/AHA Task Force
I	Sx w/ greater than normal activity	A	CHF risk factors. No sx or structural abnorm.
II	Sx w/ normal activity	B	⊕ structural dz. No sx
III	Sx w/ minimal activity	C	⊕ structural dz. Current or prior HF symptoms
IV	Sx at rest	D	End-stage HF, sx at rest
Mortality w/o Rx: NYHA I: 5% 1 y, 19% 4 y; II or III: 15% 1 y, 40% 4 y; IV: 63% 1 y. Prognostic calculator: Seattleheartfailuremodel.org (Circulation 2006;113:1424).

General Treatment Principles

Referral: Cardiology for new dx, workup, periodic evaluation; HF specialist/transplant center for pts w/ severe disease; consider advanced HF referral if:

• severe symptoms of HF with dyspnea at rest or minimal exertion (class IIIb–IV),
• episodes of fluid retention or evidence of peripheral hypoperfusion at rest,
• inability to exercise, 6-min walk distance ≤300 m, peak VO₂ <12– 14 mL/kg/min (as determined by cardiopulmonary exercise testing)
• ≥1 HF hospitalization in past 6 mo

HFpEF/Diastolic dysfunction: Focus on tx of underlying conditions; salt restriction & cautious use of diuretics; control HTN & rate in AF; ACEI/ARB assoc w/ ↓ mortality in observational but not RCT (JACC 2013;62:e147; JAMA 2012;308:2108), use βB if hx ischemia (NEJM 2004;351:1097);

referral for cardiac rehabilitation

Asymptomatic ↓EF: Initiate Rx (ACEI + βB as tolerated) when EF

≤40%

Treat reversible causes: Thyroid disease, tachycardia, anemia, hemochromatosis, HTN, renovascular disease, CAD, valvular disease, EtOH/cocaine abuse, malnutrition, SLE, sarcoid; CPAP in OSA & HF: ↑ EF & exercise tolerance but = survival (NEJM 2005;353:2025)

Lifestyle: Smoking/EtOH cessation, salt restriction (<2 g/d), fluid restriction (1.5–2 L/d), wt loss; nutrition referral; cardiac rehab & supervised exercise (JAMA 2009;301:1439; 2009;301:1451)

 

Immunizations: Influenza & pneumococcal vaccination

Care coordination/self-management: Daily wts (pt to call if ↑ >2–3 lb for 2 straight days), edema check, symptom log; prompt f/u appt (7–14 d for in-person visit, or telephone follow-up within 3 d after d/c for CHF flares (JAMA 2010;303:1716); involvement of cardiology, RNs, social workers, nutrition; frequent pt education & clinician contact; consider multidisciplinary HF-disease management program for those at high- risk of readmission

HF postdischarge visit goals: (1) initiate/titrate guideline-directed med tx, (2) identify causes of HF and barriers to care, (3) assessment of volume status and BP, adjust HF therapy accordingly, (4) check renal function and electrolytes, (5) HF education, self-care, emergency plan and adherence, (6) assess need for palliative care

Medications to avoid/use cautiously in HF pts: NSAIDs, corticosteroids, CCB (except amlodipine, felodipine (Br Heart J 1995;73:428; NEJM 1996;335:1107)), thiazolidinediones, metformin (can ↑ HF sx; JAMA 2003;290:81), cilostazol, class I & III antiarrhythmics (except amiodarone), anagrelide, amphetamines, carbamazepine, dronedarone, clozapine, ergots, β2–agonists (i.e., albuterol), herbal agents (Arch Intern Med 2004;164:709); monitor patients taking metformin (can ↑ HF sx; JAMA 2003;290:81)

Correction of anemia: Controversial; IV iron in NYHA II or III pts w/ iron deficiency ± anemia did ↓ sx, ↑ QoL (NEJM 2009;361:2436); darbepoetin in pts w/ sx HF & anemia not assoc w/ clinical benefit (Circulation 2008;117:526; NEJM 2013;368:1210) while meta-analysis of erythropoiesis- stimulating agents suggests otherwise (Am Heart J 2011;161:822); further studies needed; ESAs typically Rx’ed by hematology

Anticoagulation: HF pts w/o AF have ↑ risk of stroke, DVT, PE (Circulation 2007;115:2637); for pts w/ EF ≤35% in sinus rhythm no benefit to anticoagulation w/ ASA, clopidogrel, or warfarin (Am Heart J 2004;148:157; Circulation 2009;119:1616); major society guidelines recommend against anticoagulation for systolic HF unless hx thromboembolism or AF Atrial fibrillation: No survival benefit for rate vs. rhythm control in HF pts (NEJM 2008;358:2667), but rhythm control may ↓ severe sx (Circulation 2004); amiodarone (Circulation 1998;98:2574) & dofetilide (NEJM 1999;341:857) preferred; dronedarone assoc w/ ↑ mortality in severe systolic HF (NEJM

 

2008;358:2678); if rate control used, β-blockers are preferred unless otherwise contraindicated (can use verapamil and diltiazem in HFpEF); if treatment refractory, consider AV node ablation and CRT

Patient information: JAMA 2011;306:2175; AFP 2008;77:967;

2003;68:339

Treatment of HFrEF (Circ 2013;128:e240; 2016;135:839; JACC 2009;53:e1; J Card

Failure 2010;16:475)

 

 

Treatment of HFrEF by ACC/AHA Stage
Stage	Intervention (NEJM 2003;348:2007)
A	Treat HTN, DM, HLD, CAD, afib, obesity, metabolic syndrome, thyroid dz. Risk factor reduction & healthy lifestyle (JAMA 2009;302:394). ACEI or ARB in appropriate pts.
B	Above interventions + ACEI/ARB and/or βB in appropriate pts. Consider AICD in select pts (see below). Cardiac rehab referral.
C	Above interventions + diuretics/salt/fluid restriction in appropriate pts. ACEI in all pts, BB in stable pts. Avoid drugs that may worsen HF. Consider specialist referral, aldosterone antagonists, digoxin, hydralazine/nitrates, and CRT/AICD in select pts. Cardiac rehab referral
D	VAD, transplantation or hospice.

Drugs that ↑ survival: ACEI, βB, ARB, hydralazine/nitrates (in African- Americans), aldosterone antagonists if EF<40%, ARNI

Drugs that ↓ symptoms: Digoxin, diuretics, βB, ACEI, ARBs, ARNI

 

Medications Used in Heart Failure with Reduced Ejection Fraction (NEJM 2010;362:228)
Rx Class, Starting Dose	Notes
Loop diuretics Furosemide 20 mg QD Bumetanide 0.5 mg QD Torsemide 5 mg QD Can give TID-QID; ideally q8 am, 1–2 pm	Titrate to wt ↓ 1 kg/d until euvolemic; monitor for ↓ Mg; If lack of urine output after dose, ↑ dose rather than freq; oral absorption of bumetanide/torsemide more predictable than furosemide; PO Bumetanide 1 mg ≈ torsemide 20 mg ≈ furosemide 40 mg; thiazides enhance diuresis by blocking distal Na reabsorption but may further ↓ K+/Mg2+ (NEJM 1998;339:387)
ACEIa Enalapril 2.5 mg BID Lisinopril 5 mg QD	↑ Survival in asx or sx pts w/ EF ≤35% (NEJM 1992;327:685; 1991;325:293), NYHA class II-IV (NEJM 1987;316:1429) Target dose: Enalapril 10 mg BID or lisinopril 20–35mg QD
βBa Bisoprolol 1.25 mg QD Carvedilol 3.125 mg BID Metoprolol XL 12.5 mg QD	↑ Overall & event-free survival in NYHA II–IV & EF ≤35–40% (JAMA 2000;283:1295; 2002;287:890; 2002;287:883; Lancet 1999;353:9; 2001;353; NEJM 1996;334:1349); improvement additive to ACEI (Ann Intern Med 2001;134:550); pts should be stable to avoid worsening sx;

 

	cardioselective βB (i.e., metoprolol) safe in pts w/ mild–mod reactive airway disease (COPD, asthma) (Ann Intern Med 2002;137:715). Target dose: Bisoprolol 10 mg QD or metoprolol XL 200 mg QD or carvedilol 25 mg BID
Angiotensin receptor blocker (ARB) Candesartan 4 mg QD Losartan 50 mg QD Valsartan 20 mg BID	↑ Survival in pts intolerant to ACEI w/ sx CHF & EF ≤40% (Lancet 2003;362:772); ↑ survival w/ high-dose losartan (150 mg QD) compared to low dose (50 mg QD) in pts w/ NYHA II–IV HF, EF ≤40%, & intolerant to ACEI (Lancet 2009;374:1840); candesartan ↓ risk of CV death or nonfatal MI in NYHA II–IV pts & is assoc w/ ↓ mortality risk compared to losartan (JAMA 2005;294:1794; 2011;305:175); ↑ adverse effects w/ combination of ACEI & ARB in pts w/ sx systolic HF → combo contraindicated (Arch Intern Med 2007;167:1930); use very cautiously in pts w/ hyperkalemia, HoTN, or renal insufficiency due to ACEI Target dose: Losartan 150 mg QD, candesartan 32 mg QD
(NEJM 2001;345:1667)
Angiotensin receptor neprilysin inhibitor (ARNIs) Sacubitril/valsartan fixed dose 24–26 mg BID	ARB added to inhibitor of neprilysin (enzyme that degrades natriuretic peptides, bradykinin, and other vasoactive peptides). ARNI decreased composite of CV death or HF hospitalization by 20%, similar across subgroups; ARNIs assoc w/ risk of HoTN, renal insufficiency and angioedema (NEJM 2014; 371:993) ARNI
	can replace ACEi/ARB in patients with persistently symptomatic HF to further reduce morbidity or mortality Target dose: Sacubitril/valsartan 97 mg/103 mg BID
Aldosterone antagonists Spironolactone 25 mg QD Eplerenone 25 mg QD (in pts w/ nl GFR)	↑ Survival in NYHA II–IV & EF ≤35% (NEJM 1999;341:709; 2011;364:11); monitor closely for ↑ K+; avoid in pts w/ baseline Cr ≥2.5 ♂, 2.0 ♀, or GFR ≤30 or K+ ≥5.0. Eplerenone ↓ endocrine s/e (i.e., gynecomastia) and ↑ survival in pts w/ NYHA II HF and EF ≤ 35% (NEJM 2011;364:11) or in pts w/ EF ≤40% after MI (NEJM 2003; 348:1309) Target dose: Spironolactone 50 mg
Hydralazine 25 mg TID + nitrate (isosorbide mononitrate 30 mg QD)	↑ Survival in African-Americans w/ EF ≤40% & persistent NYHA III to IV HF despite optimal medical Rx (NEJM 2004;351:2049); consider use in all patients who cannot tolerate ACEI/ARB Hydralazine assoc w/ lupus-like syndrome
Digoxin 0.125 mg QD (in pts w/ nl GFR)	Provide sx control in pts w/ EF ≤40% & NYHA II–IV despite optimal medical Rx; ↓ hospitalization for HF but not mortality (NEJM 1997;336:525); titrate to goal serum digoxin 0.5–0.9 ng/mL; ↑ levels ↑ toxicity & mortality (JAMA 2003;289:871); ✓ levels 6 h after dose
Ivabradine 5 mg BID	Blocks If channel in SA node to reduce HR in patients with HR ≥70 bpm at rest; can reduce HF hospitalization for patients with stable, chronic class II-I-II HF and LVEF ≤35% on GDMT; should not be administered to patients with MI in prior 2 mo

 

aDouble dose every 2 wk in stable HF pts; target maximally tolerated dose for each drug, or highest dose tolerated; some ACEI or βB is better than none (Eur J Heart Fail 2005;7:712)

Automatic implantable cardioverter defibrillator (AICD): ↓ Mortality by 23% in pts w/ persistent LVEF ≤35%, ischemic or nonischemic CMP, NYHA II or III HF despite optimal medical Rx for ≥3 mo (ischemic: >40 d post-MI) (NEJM 2005;352:222;225); candidates should have >1 y expected survival w/ good functional status; recent evidence for no improvement in mortality in nonischemic CM (NEJM 2016; 375: 1221)

Cardiac resynchronization therapy (CRT, biventricular pacing): ↑ NYHA functional status, ↓ sx, ↓ hospitalizations, ↓ all-cause mortality in NYHA III & IV pts w/ ↓ EF & ↑ QRS (JAMA 2007;297:2502; NEJM 2002;346:1845);

recommended in pts w/ QRS >120 ms, LVEF ≤35%, SR, NYHA II, III or ambulatory class IV despite medical Rx (best responders: LBBB + QRS

≥150 ms, women)

CRT + AICD benefits: (vs. AICD alone)

NYHA III/IV: Ischemic or nonischemic CMP pts w/ QRS >120 ms have ↑ QoL & functional status (JAMA 2003;289:2685) NYHA II/III: ↓ all- cause mortality or HF hospitalization (NEJM 2010;363:2385) NYHA I/II:

↓ ischemic or nonischemic CMP pts w/ QRS >130 ms and EF

≤30% have ↓ HF events but no mortality benefit (NEJM 2009;361:1329) Revascularization: For pts w/ EF ≤35% & multivessel CAD or proximal LAD stenosis >70%, CABG pts had ↓ morbidity and CV mortality (NEJM

2011;364:1607); CABG may also ↑ survival in patients with significant CAD

and mild–mod LV dysfunction (LVEF 35–50%)

 

VALVULAR HEART DISEASE

Evaluation (JAMA 2015;313:1050)

 

Auscultation of Murmurs (JAMA 1999;281:2231)
	Systolic	Diastolic
Early	Mitral or tricuspid regurgitation Ventricular septal defect	Aortic or pulmonic regurgitation
Middle	Aortic sclerosis, aortic stenosis, bicuspid aortic valve Atrial septal defect “Innocent” benign flow murmur

 

	HOCM Anemia or pregnancy	Mitral stenosis Tricuspid stenosis
Late	Mitral or tricuspid valve prolapse Pulmonic stenosis
Holo	Mitral or tricuspid regurgitation Ventricular septal defect
General approach: Murmurs are described by intensity (below), quality (harsh, blowing, scratchy), configuration (crescendo, decrescendo, crescendo–decrescendo), timing (systolic vs. diastolic), location, and radiation.
Murmur intensity: I: Softer than S1/S2. II: Equivalent to S1/S2. III: Louder than S1/S2, no palpable thrill. IV: Palpable thrill present. V: Loud with thrill; may be heard with slight stethoscope touch. VI: Heard without stethoscope.

Aortic Stenosis (AFP 2016;93:371; Ann Int Med 2017;166:ITC-1; JACC 2014;63:e57;

JAMA 2013;310:1490; Lancet 2009;373:956; NEJM 1997;337:32; 2002;346:677)

Etiology: Represents 20% of all pts w/ chronic valvular disease, ♂ predominance

Valvular: Calcific (age-related degenerative, most common), congenital (bicuspid or unicuspid); rheumatic (usually w/ AR & MV involvement) Subvalvular: LVOT obstruction (i.e., HOCM)

Supravalvular: Ascending aortic narrowing (e.g., William syndrome) Presentation and prognosis: If AVA <1 cm2, average survival time (AST) by symptoms:

Angina pectoris (35% of pts): O₂ mismatch due to ↑ myocardial mass; AST: 5 y Exertional syncope (15%): Sudden ↓ in CO due to mechanical obstruction or arrhythmia; AST: 3 y Exertional dyspnea (50%): Due to ↑ pulm capillary pressure; AST: 2 y CHF:

Systolic & diastolic dysfunction; AST: 1.5–2 y

Cardiac cachexia: Marked fatigability, weakness, peripheral cyanosis, orthopnea, PND, pulmonary edema; severe pHTN leading to RV failure

Exam: Systolic crescendo–decrescendo ejection murmur (also consider PS); timing of murmur peak (not volume) determines valve severity (early peaking → mild, late peaking → severe), murmur best heard at the base of the heart & radiates to the carotids; Gallavardin phenomenon: Radiation to apex; Pulsus parvus et tardus w/ slow rise & delayed sustained peak (severe disease only)

 

Paradoxic splitting of S₂ w/ eventual loss of S₂ w/ severe disease; S₄ due to LVH

Workup: ECG: LVH, ST depression, TWI (“strain pattern”) in I, aVL & V₅–V₆; TTE: Peak/mean gradients, jet velocity; natural progression w/ reduction of 0.1 cm2/y & ↑ in mean gradient of 7 mmHg/y (Circulation

2008;118:e523)

Cath: Eval for CAD prior to surgical intervention (incidence >50% in age >45 y), or confirm severity of AS if TTE & PE or clinical findings do not correlate

 

Classification of Aortic Stenosis (JACC 2014; 63(22))
Stage	Aortic Valve Area (cm2)	Aortic Jet Velocity (m/s)	Mean Gradient (mmHg)	Check TTE
Mild	>1.5	2–2.9	<20	q3–5y
Moderate	1–1.5	3–3.9	20–39	q1–2y
Severe	<1.0	≥4	≥40	q6–12mo
Very severe		≥5	≥60	Cardiology referral

Sclerosis: Focal thickening or calcification of valve cusps w/ a peak transaortic velocity ≤2 m/s; determination of valve area, jet velocity; precursor to mild AS

Treatment: Avoid isometrics (even if asx if severe AS); dehydration/hypovolemia

Medical: βB, ACEI for HTN & CAD; statins do not ↓ progression or diastolic dysfunction (Cardiovasc Ultrasound 2011;9:5; Circulation 2010;121:306); caution w/ antihypertensive Rx in severe AS; stenosis limits cardiac ability to ↑ BP

Surgical: Indicated in symptomatic/severe disease, or if progressive LV dilation, LVEF <50%, or aneurysmal, expanding aortic root or ascending aorta Percutaneous valvuloplasty: Temporary bridge to surgery for severely ill pts

Percutaneous valve replacement: Offered for high-risk surgical pts;

↓ mortality but ↑ incidence of stroke & vascular events, recent data suggest safety/efficacy in intermediate-risk pts (STS risk score = 4–8%) with similar rates of death or disabling stroke (Ann Int Med

 

2010;153:314; NEJM 2010;363:1597; 2016; 374:1609)

Aortic Regurgitation (Circulation 2005;112:125; JAMA 1999;281:2231; NEJM

1997;337:32; 2004;351:1539; 2006;355:385)

Etiology: Valvular vs. aortic root disease; valvular: Congenital (bicuspid, VSD), myxomatous degeneration, endocarditis, rheumatic (usually w/ assoc MV disease), nonpenetrating trauma; aortic root dilation → leaflet malcoaptation; idiopathic, cystic medial degeneration (Marfan’s, Ehlers Danlos), annuloaortic ectasia, osteogenesis imperfecta, HTN; retrograde type A aortic dissection, syphilis, ankylosing spondylitis

Presentation: Acute: Pulm edema ± cardiogenic shock, diffuse ST changes on ECG; Chronic: Palpitations, exertional dyspnea, orthopnea, PND, excessive diaphoresis; anginal CP (usually unresponsive to NTG) Exam: Wide pulse pressure if severe; high-pitch, decrescendo diastolic murmur (shorter murmur w/ more severe AR); Austin–Flint murmur: Soft, low-pitch rumbling mid-diastolic murmur; Corrigan pulse (“water- hammer”), capillary pulsations if severe & chronic

Maneuvers: Intensified w/ handgrip or squatting (↑ peripheral vascular resistance)

Workup: ECG: LVH, if severe → global ST depressions, TWI (“strain pattern”) in I, aVL & V₅–V₆; LA dilatation, QRS prolongation (assoc w/ poor prognosis); TTE: If severe, monitor LV function q6–12mo Treatment: Avoid isometric exercises; diuretics, vasodilators (ACEI,

dihydropyridine CCB, hydralazine); SBP <140; surgical replacement >

repair (rare), indications: Severe/symptomatic or if asymptomatic w/ LV dilation or dysfunction

Mitral Stenosis (ACC/AHA guidelines Circ 2017; Lancet 2009;374:1271; NEJM

1997;337:32)

Etiology: Rheumatic >>> calcification (ESRD or calciphylaxis); post- MV repair/replacement; congenital (mitral ring, parachute); rarely, myxoma, valvulitis (SLE, RA, amyloid, carcinoid), infiltration (e.g., mucopolysaccharidoses), radiation

 

Classification of Mitral Stenosis (JACC 2014; 63:2438)
Stage	Definition	Valve Anatomy	Hemodynamic Consequences	Check TTE

 

A	At risk of MS	Valve doming during diastole	None	N/A
B	Progressive MS	Valve doming during diastole, MVA >1.5 cm2	Mild–moderate LA enlargement	q3–5y
C	Asymptomatic severe MS	MVA <1.5 cm2, or <1.0 cm2 in very severe MS	Severe LA enlargement; PASP >30 mmHg	q1–2y
D	Symptomatic severe MS	MVA <1.5 cm2, or <1.0 cm2 in very severe MS	Severe LA enlargement; PASP >30 mmHg	q6–12 mo

History: Pulm congestion (dyspnea, hemoptysis); periph edema, tachycardia (↓ diastolic filling), ↓ exercise tolerance (can’t ↑ CO); AF: Loss of “atrial kick” (essential w/ ↑ LA pressure) can precipitate HF Exam: Soft, low-pitched mid-diastolic rumble at apex (best if in L lateral decubitus); loud, delayed S_1, opening snap (early diastolic, in expiration). Maneuvers: ⊕ murmur at ↑HR (exercise such as sit ups, squats)

Workup: ECG: Left atrial abnorm, AF, RVH (late stage); CXR: LA dilatation = straight upper L heart border; pulm congestion, ↑ main PA size; TTE: Transvalvular peak & mean gradients, valve area, restriction, & thickness of leaflets, RVSP

Treatment: Na restriction, diuresis for pulm congestion; rate control to

↑ diastolic filling time

Anticoagulation: Indicated if AF, or prior embolic event, or LAA thrombus

Percutaneous balloon valvotomy: In symptomatic pts with severe MS; contraindicated if heavily calcified valve, LAA thrombus & ≥ mod MR; consider in asymptomatic very severe MS (MVA <1.0 cm2) with favorable anatomy Surgical: Valves generally replaced (not easily repairable); indicated in pts w/ significant MR, severe valve distortion not amenable to percutaneous intervention; 10-y survival 70%; worse outcomes if ↓ CO, pHTN, & RV dysfunction

Mitral Regurgitation (NEJM 1997;337:32; 2001;345:740)

Etiology: Caused by damage or distortion of MV apparatus; it is critical to distinguish between primary and secondary MR. Primary: Components of valve (leaflets, chordae, papillary muscle) cause valve

 

incompetence, caused by myxomatous degeneration, IE, CTD, RHD, cleft mitral valve, radiation; acute MR due to pap muscle rupture during MI Secondary/functional: Valve is normal, but an abnormal/dilated LV causes annular dilation and prevents valve coaptation; acute funct MR due to inferior wall hypo/akinesis

Presentation: AF (↑ LA pressure); Pulm congestion/HF (LA pressure

→ ↑ pulm pressures→ fatigue, dyspnea); Right sided HF (↑ LA pressure→ pHTN → ↑ RV pressure)

Exam: Holosystolic, decrescendo murmur at apex, radiating to axilla; w/ posterior mitral leaflet prolapse/flail, regurgitant jet is eccentric & directed anteriorly, striking the LA wall adjacent to the aortic root, so sound transmitted to the base; soft S₁, low-pitched S₃ (tensing of

papillary muscles & chordae tendineae). In acute MR: S₄, shorter, softer murmur that is often hard to hear.

Maneuvers: ↑ w/ isometric exercise (e.g., handgrip); ↓ by strain phase of Valsalva

Diagnostic workup: ECG: LAE, AF ± LVH, if pulm HTN may have RV strain pattern (late stages); TTE: Estimate of severity based on color Doppler, regurgitant volume/fraction, jet width

Treatment: Avoid isometric exercises, keep afterload/BP low normal

Medical: Na restriction, BP control, diuresis; if AF, digoxin, βB. If secondary MR, medical therapy for symptomatic pts with systolic dysfunction Surgical:

Primary severe MR: Sx pts w/ LVEF >30%, asx pts w/ LVEF 30– 60% and/or LVESD ≥40 mm. Prefer MV repair >> replacement. Consider repair in asx pts, with low surgical risk (STS risk score

<1%) or those with atrial fibrillation and/or pulmonary hypertension (PASP >50 mmHg); if AF, may have valve reconstruction + annuloplasty ± LA Maze procedure or RFA. Patients with sx despite max med therapy and with prohibitive surgical risk can consider transcatheter mitral valve repair Secondary: MV repair or replacement may be considered for severely sx patients who have sx despite GDMT +/– CRT for HF or those undergoing other cardiac surgery

Mitral Valve Prolapse (Circulation 2002;106:1355; NEJM 1997;337:32; 1999;341:1;

2010;363:156)

 

Etiology: Thick, redundant myxomatous mitral leaflets & chordal elongation. If both leaflets involved/thickened: Barlow valve; Bimodal distribution: ♀ 15–30 y; ♂ >50 y. Pts w/ mitral valve prolapse have an approximately 1%/y risk of CHF, endocarditis, CVA, significant MR, or CHF

Presentation: Often asymptomatic but can be assoc w/ syncope, atypical CP, SCD (rare); Palpitations: Related to PVCs, paroxysmal SVT & VT, AF

Exam: Mid or late systolic click, after S₁ (sudden tensing of slack, elongated chordae tendineae or prolapsing mitral leaflet); Maneuvers: Earlier with standing, strain portion of Valsalva (↓ LV volume), diminishes w/ squatting & isometric exercises

Workup: ECG: LA enlargement, nl, biphasic, or inverted Tw in II, III, or

aVF; Echo: Quantify MR, est PA pressure, LV size/function Treatment: βB for CP & palpitations; Surgical: Valve repair if presence of significant MR as above (NEJM 2009;361:2261)

Tricuspid Regurgitation (JACC 2014; 63:2438)

Etiology: 20% are primary: Rheumatic, congenital (Ebstein), myxomatous degeneration, endocarditis, trauma from procedures (pacemaker, RV biopsy); 80% are secondary to RV dilatation Presentation: Often asx until advanced severe TR; right-sided volume overload (periph edema, bloating, ascites)

Exam: Holosystolic decrescendo murmur at RLSB; mod–sev TR audible over liver

Workup: ECG: RA hypertrophy, signs of RV dx (RVH, old IMI). TTE; if chronic severe TR, check LFTs, abdo US for cardiac cirrhosis Treatment: Diuretics, pulmonary vasodilators if pHTN; surgery if other valve sx and mod-sev sx TR, or mild–mod TR if annulus dilated/prior Rt HF; may consider for asx severe primary TR if progressive moderate/severe RV dilatation/dysfunction in the absence of pHTN

Tricuspid Stenosis (JACC 2014; 63:2438)

Very rare; generally rheumatic, and occurs along with tricuspid regurgitation; often presents as abdominal discomfort due to hepatic congestion; may be treated w/ percutaneous valvuloplasty if ≤mild TR; otherwise, TVR if sx and severe TS

 

Pulmonary Regurgitation (JACC 2014; 63:2438)

Etiology: Most often congenital, either primary or after valvotomy/right ventriculotomy for childhood repair of pulmonic stenosis (see “Adult Congenital Heart Disease”); endocarditis, carcinoid. Mild-moderate PR without another pathology is not concerning as long as RV normal size/function

Presentation: Often asx until severe; right-sided volume overload (periph edema, bloating, ascites), dyspnea, palpitations (Aflutter). If RV dilatation, may present w/ SCD/VT

Exam: Early diastolic blowing murmur at LUSB; louder w/ inspiration (more venous return)

Workup: ECG: RA hypertrophy, signs of RV dilation TTE: RV size, function

Treatment: Diuretics; BB and ACEi may be beneficial for RV remodeling; surgery for severe PR and symptoms or RV enlargement

Pulmonic Stenosis (JACC 2014; 63:2438)

Etiology: Most often congenital (valvular stenosis, subpulmonic or supravalvar stenosis); carcinoid, tumors possible

Presentation: Dyspnea, right-sided HF

Exam: Systolic ejection murmur at LUSB; pulmonic stenosis opening click becomes softer w/ inspiration (only Rt-sided heart sound to do that)

Treatment: Valvulotomy (with great long-term results for ≤ moderate isolated PS) vs. PVR depending on pathology

 

AORTIC DISEASE

Background (AFP 2006;73:1198; 2015;91:538; Circulation 2006;113:e463; 2008;117:242;

2010;121(13); JAMA 2007;297:395; Lancet 2005;365:1577; NEJM 2014;371:2101)

Location: Thoracic (TAA), abdominal (AAA), thoracoabdominal or multiple

 

Aortic Diameter in Health and Disease
		Upper Limit Normal (cm)		Abnormal (cm)
		Women	Men	Women	Men

 

Atherosclerotic: Most common, assoc w/ typical atherosclerotic risk factors (smoking, age >65, HTN, as well as HLD, CAD/PVD, & FHx); also assoc w/ COPD & PCKD

Congenital: Marfan, Ehlers–Danlos, association of TAA w/ bicuspid AoV

Infectious: Bacterial inflammation of aortic wall caused mainly by Staph & Salmonella Inflammatory AAA (5–10% cases): Pts typically p/w back/abdominal pain; CT/MRI notable for periaortic inflammation & fibrosis; ESR/CRP ↑ (JAMA 2007;297:395)

Prevalence: AAA: 1.3–8.9% in ♂ & 1–2.2% in ♀, ↑ w/ age; ∼10k deaths/y

Risk factors: AAA: Age, ♂, smoking, HTN, HLD, bicuspid AV, CAD or PAD, FHx; TAA: Incl most AAA risk factors, consider familial syndrome, genetic syndromes, e.g., Marfan, Loeys–Dietz, and inflammatory disorders, e.g., GCA, Takayasu’s

Dissection: If acute → ER; Risk factors: HTN, bicuspid AoV, coarctation, h/o rapid progression, connective tissue dz (e.g., Marfan), cocaine, trauma, recent cath (JAMA 2002;287:2262); type A (TAA: ascending aorta and/or aortic arch) → surgical emergency; type B (descending TAA w/o involvement of the ascending aorta, or AAA) → medically managed with BP control, unless perfusion to kidneys/other organs compromised

Evaluation (Circulation 2005;111:816; EHJ 2014;34:2873; JAMA 2009;302:2015;

2015;313:1156)

History: Both TAA and AAA are often asx and incidental; may have vague, chronic CP/abdominal radiating to back/flank

Exam: Often unremarkable; TAA: Rarely evident on exam, should eval for associated pathology, e.g., AoV dz. AAA: Sensitivity of palpation for AAA 4–4.9 cm = 50%, >5 cm 76%; limited by body habitus (JAMA

 

1999;281:77)

Red flags: Suspect dissection in pts w/ risk factors (above) & abrupt onset of severe, “tearing or ripping pain,” radiating to back, mediastinal or aortic widening on CXR, or >20 mmHg BP difference between arms; If suspected → ED (Arch Int Med 2000;160:2977)

Screening: If aneurysm identified, perform assessment of the entire aorta and AoV

AAA: USPSTF grade B recommendation for men ages 65–75 who have ever smoked to receive one-time screening ultrasound; grade C recommendation for one-time screening in male nonsmokers ages 65–75; no routine screening recommended for women unless clinical history warrants evaluation (EHJ 2014; 34:2873– 2926); CT or MRA useful for inflammatory AAA & for perioperative eval to define anatomy; consider targeted screening of 1st-degree relatives of patients with AAA TAA: Recommended for 1° relatives of pts w/ TAA to r/o familial syndrome; preferred diagnostic strategy is CT/MR angiography or TTE/TEE (similar high sens/spec) (Arch Intern Med 2006;166:1350); MRI preferred if aortic root involvement; consider evaluation of 1° relatives of pts w/ bicuspid AoV for asymptomatic TAA and/or bicuspid AoV

Surveillance of known aortic aneurysms:

TAA: Rupture risk ↑ w/ larger diameter, ↑ rate of expansion; repeat imaging at 6 mo & then annually if stable; also screen for coexisting AAA AAA: Rupture risk ↑ w/ larger diameter, ↑ rate of expansion, HTN, smoking; some studies suggest for small AAA (<5.5 cm), longer surveillance intervals may be used (JAMA 2013;309:806), however optimal screening intervals are debated

 

AAA Surveillance (EHJ 2014; 34:2873–2926; Eur J Vasc Surg 2011; S1–S58; Circulation 2013; 127)
AAA Diameter	Interval (ACC/AHA)	AAA Diameter	Interval (ESC)
4–5.4 cm	q6–12mo	4–5–5.4 cm	q12mo
Annual rupture risk by diameter (cm): <5.5:		4–4.4 cm	q2y
≤1%, 5.5–5.9: 9.4%, 6–6.9: 10.2%, ≥7:		<4 cm	q3y
32.5%

Treatment (Circulation 2006;113:e463; 2008;117:1883; 2010;121:1544; JAMA

2009;302:2015)

 

Medical: Smoking cessation, manage HTN, HLD; limited evidence for βBs, ACEI, abx (PLoS ONE 2008;3:e1895); statins may have mortality benefit (Am J Cardiol 2006;97:279); benefits of ASA likely to outweigh risk given ↑ prevalence of CAD in this population

Surgical:

AAA: Repair if diameter >5.5 cm, expansion >5 mm in 6 mo, complications (e.g., hematoma, ulcer, infection), genetic syndrome, pregnancy or if pt is symptomatic; consider repair in ♀ if >5 cm (Lancet 1998;352:1649; NEJM 2002;346:1437) TAA: Repair if >5.5

cm; consider repair >5 cm if sx, rapid expansion, FHx dissection, at experienced center in low-risk pt, familial syndrome (Marfan, Ehlers–Danlos) (JACC 2016;133:680); consider repair if >4.5 cm if Loeys–Dietz, or FHx dissection at <5 cm Endovascular repair: Available for descending TAA & AAA; may be considered for pts ineligible for open repair; typically requires healthy aorta below renal arteries & adequate iliac arteries; similar all-cause mortality (J Vasc Surg 2011;53:1167; Nat Rev Cardiol 2013;10:122; NEJM 2010;362:1863;

2015;373:328), but requires surveillance imaging, has higher leak rates/reoperation.

Patient handouts: AFP 2006;73:1205 & JAMA 2009;302:2050

 

 

CAROTID DISEASE

Background (JAMA 2008;300:81; NEJM 2000;342:1693; 2013;369:1143; Neurology

2003;60:1429)

Epidemiology: ∼700,000 stroke/y in US (85% ischemic); internal carotid artery (ICA) disease prevalence = 0.5% by age 50, 10% by age 80 (Stroke 2010;41:1294); 15% strokes are caused by ICA disease; ∼36% of pts who p/w TIA are found to have ICA disease

Pathophysiology: Plaques form in common carotid bulb, extend to ICA → ulceration & rupture → embolization → TIA or stroke

Risk factors: Smoking (RR = 2), African ancestry, HTN, DM, metabolic synd, ♂, HLD

Asymptomatic: Defined as no prior hx TIA or stroke; asx pts w/ a stenosis ≤60% → 1.6%/y risk of stroke; ≥60% stenosis → 3.2%/y risk of stroke

 

Symptomatic: Defined by hx TIA (transient focal neuro deficit or amaurosis fugax) or nondisabling stroke (in a vascular territory supplied by a stenosis) w/in the last 6 mo; carries ↑ risk of future vascular events so managed more aggressively

Evaluation (Circulation 2011;124:e54; JAMA 2015;313:192; Lancet 2006;367:1503)

Screening: Routine screening of asx pts not recommended (USPSTF) (Ann Intern Med 2007;147:854); new stroke, TIA, or carotid bruit should prompt testing; consider screening in high-risk pts with ≥2 of HTN, HLD, smoking, FHx of atherosclerosis <60 y or CVA (IIB, LOE C) or in pts w/ symptomatic PAD, CAD, or aortic aneurysm (IIb, LOE C)

History and exam: Most asx cases detected due to a carotid bruit on exam; assess for TIA/stroke sx (see “Stroke”) incl homonymous hemianopsia, sensory loss, or motor deficits (NEJM 2005;352:2618); in comparison, vertebrobasilar insufficiency → cranial nerve loss, diplopia, vertigo, or dysarthria (NEJM 2005;352:2618)

Diagnosis: Duplex U/S: Most widely used & studied; evaluates artery based on peak-systolic velocity (85–92% sensitive, 77–89% specific, operator dependent, should be performed in an accredited lab) (J Vasc Surg 1993;17:152); MRA: 88–97% sensitive, 89–96% specific (Stroke

2008;39:2237); CTA: 68–84% sensitive, 91–97% specific (Stroke 2004;35:2306); MRA tends to overestimate & CTA tends to underestimate degree of stenosis (J Neurol Neurosurg Psychiatry 2002;73:21)

Surveillance: Periodic surveillance with yearly duplex is reasonable for patients with >50% stenosis identified by prior testing; longer intervals or cessation of surveillance may be appropriate after stability is proven

Management (Circulation 2011;124:e54; JAMA 2013;310:1612; NEJM 2008;358:1617)

Medical management: Manage HLD (see “Dyslipidemia”), HTN (see “Hypertension”), DM (see “Diabetes Mellitus”), smoking (see “Tobacco Use”); education about s/sx of TIA, stroke, & amaurosis fugax

 

Antiplatelet Agents for Stroke Prevention (Circulation 2011;124:e54; J Vasc Surg 2009;50:431)
Indication	Regimen
Asymptomatica	ASA 81 mg QD or clopidogrel 75 mg QD
2° prevention	ASA/dipyridamole 25/200 mg BID or ASA 75–325 mg QD or clopidogrel 75 mg QD
S/p carotid artery stenting	ASA 81–325 mg QD & periprocedural clopidogrel

 

	(loading dose + 75 mg QD ×4–6 wk)
S/p CEA (Chest 2008;133:630S)	ASA/Dipyridamole 25/200 mg BID or ASA 81–325 mg QD or clopidogrel 75 mg QD

aBenefit in stroke prevention is not clearly established, though can prevent MI and other ischemic CV events.

Revascularization: Choice of interventional tx w/ carotid endarterectomy (CEA) or carotid artery stenting (CAS) is controversial & evolving, thus a vascular medicine or surgery consult is reasonable for any ICA stenosis >50%; following revascularization (CEA or CAS), reasonable to perform noninvasive imaging at 1 mo, 6 mo, and yearly to assess patency and exclude new or contralateral lesions Asymptomatic: Consider CEA in pts w/ ≥70% stenosis on U/S; if ultrasound shows moderate stenosis (50–69%) despite high clinical suspicion, consider CTA/MRA for further evaluation; CEA pts should have reasonable life expectancy & be a good surgical candidate; CEA should be done by experienced surgeons in center w/ <3% morbidity/mortality; NNT to prevent 1 stroke in 3 y = ∼33 pts (Cochrane Database Syst Rev 2005;CD001923); CAS controversial as effectiveness not studied against medical therapy alone (Crest, NEJM 2010;363:11); CAS noninferior to CEA in ASx pts (NEJM 2016;374:1011)

Symptomatic: In good surgical candidates who have reasonable life

expectancy, interventional options include (Cochrane Database Syst Rev 2011;

NEJM 1991;325:445):

CEA: Indicated for patients at average or low surgical risk who suffer nondisabling CVA or TIA within 6 mo if ipsilateral ICA is >70% stenotic and rate of perioperative stroke is <6%; CEA timing: Greatest benefit if done ≤2 wk for mild stroke/TIA to avoid early CVA risk (Lancet 2004;363:915) Stenting (CAS): Indicated as alternative to CEA for symptomatic pts at low–intermediate risk for complications and anticipated rate of perioperative stroke or mortality is <6% in patients with anatomy suitable to endovascular intervention; other clinical scenarios favoring CAS include high-risk surgical patients, restenosis after prior CEA or CAS, FMD-related disease or stenosis due to XRT; ↑ risk of stroke/death & ↓ risk of MI w/in 30 d of procedure as compared to CEA; long-term outcomes similar; pts ≥70 y have 2× ↑ risk periprocedural stroke or

 

death w/ stenting vs. CEA (Lancet 2010;376:1062; NEJM 2010;363:11) <50% stenosis: CEA nonbeneficial or harmful

Total occlusion: Intervention is contraindicated (Class III)

Risk modeling: stroke.ox.ac.uk

Patient education: ncbi.nlm.nih.gov/pubmedhealth/PMH0004669

 

 

PERIPHERAL ARTERY DISEASE

Background (AFP 2013;88:306; Am J Med 2010;123:790; Circulation 2013;127:1425; JAMA

2006;295:536; 547)

Definition: Atherosclerosis, most commonly found in the aorta, iliac, & LE arteries; Critical limb ischemia is severe PAD w/ e/o chronic (>2 wk) of rest pain, nonhealing wounds, ulcers, or gangrene (JAMA Surgery 2016;151:1070)

Epidemiology: ∼20% of adults > 55 y & is assoc w/ ↑ risk for CV events & all-cause mortality

Risk factors: Age > 40 y, race (non-Hispanics & pts of African ancestry disproportionately affected, even after controlling for risk factors), smoking (5-fold ↑ in PAD compared to lifetime nonsmokers), DM (risk doubles w/ impaired glucose tolerance, up to 4-fold ↑ w/ DM), HTN (independent risk factor, ↑ severity assoc w/ ↑ risk), HLD, FHx, other atherosclerosis, e.g., coronary, carotid, mesenteric

Evaluation (Ann Int Med 2007;ITC3–1; JACC 2017;69:e71; NEJM 2001;344:1608; 2016;374:861)

History: Claudication: Exertional leg pain relieved w/ rest; 50% of PAD pts asx; atypical sx (exercise intolerance, joint pain, or limb numbness) more common in ♀; pain at rest suggests critical limb ischemia = 50% risk of amputation or death at 1 y

Exam: ↓ or absent distal pulses, bruits, but can also be nl; look for ulcers, gangrene, elevation pallor and dependent rubor, and pulses/bruits in other vascular beds

Ankle–brachial index (ABI): Systolic ankle to systolic arm pressure; simple, inexpensive, noninvasive doppler SBP of leg (higher of dorsalis pedis or posterior tibial arteries) divided by higher SBP of right/left brachial arteries (NEJM 2009;361:e40); pts w/o sx should not be screened

 

for PAD (JAMA 2016;316:1486)

ABI ≤0.9: Abnormal, 0.91–0.99: Borderline, 1.0–1.4: Normal, ≥1.4: Noncompressible calcified arteries won’t compress w/ cuff; ∴ falsely ↑ SBP reading Exercise treadmill ABIs: Consider in pts w/ borderline/normal ABIs with exertional non–joint-related leg discomfort

Other studies: Duplex U/S, CTA, & MRA used more for endovascular or surgical revascularization planning; consider screening for AAA in patients with symptomatic PAD

Contrast angiography: Gold standard, only performed if plan for endovascular tx

 

 

 

Treatment (Circulation 2006;113:1474; J Vasc Surg 2007;45:S5; Mayo Clin Proc 2008;8:944)

 

Goals: Sx relief, mgmt of related CV diseases (CAD, stroke) Risk factor modification: Smoking cessation assoc w/ ↓ progression, rates of amputation, incidence of rest ischemia;

aggressive DM, HTN, HLD management; structured exercise can ↑ walking distance by 100–150%, comparable to surgery Pharmacologic therapy

Anti-PLT: ASA 75–325 mg; clopidogrel may be superior (CAPRIE Lancet 1996;348:1329) to ↓ risk MI, CVA & vascular death in pts w/ sx PAD (class I) or ASx PAD (class IIa); utility of antiplatelet use in borderline ABI (0.91–0.99) is uncertain; role of dual antiplatelet therapy (aspirin and clopidogrel) in PAD is uncertain in pts who have not undergone revascularization Vorapaxar: Adding vorapaxar to existing antiplatelet therapy ↓ acute limb ischemia and peripheral revascularization, but did not ↓ risk of CV death, MI or CVA (Circulation 2013;127:1522), practice guidelines offer as IIb recommendation Cilostazol (PDE inhibitor): Improves sx and walking duration in claudication

Revascularization: Indications: Claudication that interferes w/ activity, ischemic rest pain, nonhealing ulcer/gangrene

Endovascular: 1st choice due to ↓ morbidity/mortality compared to surgery

Surgery: Indicated if endovascular approach is not possible or if recurrent failure of endovascular approach occurs; when surgery is chosen, autologous vein bypass to the popliteal artery is preferred over prosthetic grafts

Follow-up after revascularization: Periodic clinical evaluation including reassessment of cardiovascular risk factors and limb symptoms; pts undergoing revascularization should receive periodic ABIs and duplex ultrasound

Patient information: JAMA 2009;301:236

 

 

LOWER EXTREMITY EDEMA AND ULCERS

 

LOWER EXTREMITY EDEMA

 

Background (AFP 2005;71:2111; 2013;88:102)

Causes: Δ in hydrostatic/oncotic pressure, ↓ lymph drainage, ↑ capillary permeability

Unilateral/asymmetric DDx: DVT, cellulitis, lymphedema, venous insufficiency, popliteal (Baker) cyst, ruptured muscle/tendon Bilateral/symmetric DDx: CHF/RHF, nephrotic syndrome, cirrhosis, venous insufficiency, malnutrition, hypothyroidism, lymphatic disease, IVC thrombosis, lipedema, pregnancy/premenstrual or idiopathic, vasculitis (rare), Meds: CCB (amlodipine), steroids, estrogens, hydralazine, thiazolidinediones, diazoxide, pramipexole, minoxidil, NSAIDs (in CHF or cirrhosis), docetaxel

Evaluation

History: Onset (acute vs. chronic), location, assoc sx (dyspnea, orthopnea, pain, urinary), hx CAD/CHF/HTN/DM/EtOH/clotting, medications; hx immobility, malignancy, surgery (i.e., LN dissection venous harvest for CABG), radiation or cath, filariasis (where endemic), recurrent cellulitis/lymphangitis, prior DVT; consider OSA → pHTN Exam: HEENT (periorbital edema), lungs (crackles), CV (JVP, TR, RV heave, S₃/S₄), abdominal (HSM, pulsatile liver, ascites); lower extremities (✓ limb circumference, ✓ peripheral pulses, e/o venous insufficiency); pattern of edema involving dorsal foot & toes (Stemmer sign) suggests lymphedema; sharp demarcation at ankle, sparing the foot suggests lipedema

Diagnostics: As dictated by hx; consider BUN/Cr, LFTs including

albumin, U/A for protein, blood, D-dimer or venous duplex U/S for unilateral/bilateral disease; TTE, CXR, BNP, D-dimer, TFTs, CBC, per clinical suspicion

Treatment

General measures: Treat underlying etiology; low salt diet (<2 g/d), properly fitted compression stockings (>20 mmHg), fluid restriction, limb elevation (30 min QID)

For hypervolemic states: Loop diuretics (+ spironolactone in cirrhosis) Diuretics: Not effective in venous insufficiency; benefit limited to hypervolemic states; 1st line is loop diuretic; monitor for ↓ K, AKI, dehydration

 

Patient information: AFP 2005;71:2118

Lymphedema (AFP 2013;88:online; Am J Med 2001;110:288; BMJ 2000;320:1527)

Causes: ↓ Lymphatic flow due to LN dissection, XRT, malignancy, filariasis, recurrent cellulitis, obesity, congenital, RA, psoriasis Diagnosis: Localized, nonpitting, gradual swelling/heaviness of limb, including involvement on the dorsum of the foot, worse at day’s end; does not improve w/ recumbency; cutaneous fibrosis, dry/scaly skin, peau d’orange, ⊕ Stemmer sign (unable to lift skin at base of upper surface of 2nd digits); edema may be monitored by measuring limb circumference at set points (i.e., wrists); MRI or CT helpful if dx unclear; consider malignant lymphatic obstruction in new or worsening lymphedema

Complications: Discomfort > cellulitis >> lymphangiosarcoma (particularly in LE)

Prevention: Skin/nail care to prevent infection; avoid tight clothing and dependent positioning for long periods; avoid phlebotomy, vaccination, IVs in affected limb; hot climates, baths, & saunas may exacerbate; encourage wt loss; ROM & wt exercises

Treatment: Manual lymph drainage/compression (bandages, hose, intermittent pneumatic compression); for severe cases, surgery & cold laser tx (data unclear); Diuretics not beneficial

CHRONIC VENOUS DISEASE

 

Background (JAMA 2012;308:2612; J Vasc Surg 2011;53:2S; NEJM 2006;355:488; 2009;360:2319)

Definition: Clinical syndrome due to ↑ pressure in venous system, 2/2 obstruction/reflux

Pathophysiology: Incompetent valves/thrombosis → reflux → stasis

→ pain, edema, dermatitis, lipodermatosclerosis (circumferential hyperpigmentation, induration), ulcers

Epidemiology and risk factors: Overall prevalence of 50% in adults

(BMJ 2007;335:83; NEJM 2006;355:488; 2009;360:2319); incidence ↑ w/ age,

pregnancy, ⊕ FHx, obesity, hx LE trauma, DVT; following DVT, cumulative rates 7% at 1 y, 14% at 5 y, & 20% at 10 y

 

Venous Disease Spectrum (BMJ 2007;335:83; NEJM 2009;360:2319)
Signs	Disease	Prevalence (%)
Telangiectasias	Dilated dermal veins (“spider veins”)	50–85
Varicose veins	Dilated, tortuous, SC veins	10–40
Edema, pain, ulcers	Deep, usually w/ venous reflux	1–16

History: Pain (↑ at night, ↓ w/ elevation, exercise), heaviness/achiness, cramps, itching

Exam: Erythema, lipodermatosclerosis (hyperpigmentation + induration), ulcers (above ankle, classically medial, w/ irregular/sloped borders), bleeding

Varicose veins: SC, tortuous dilated veins >3 mm; may hemorrhage, thrombose, or → thrombophlebitis; cosmetically distressing; categorized by CEAP classification involving clinical signs, etiology, anatomy and pathophysiology, scored 0–6; scores >2 warrant referral to vascular specialist (AFP 2008;78:1289; J Vasc Surg 2009;49:498)

Stasis dermatitis: Eczematous reaction: Pruritic, erythematous, papular rash w/ overlying scale; simultaneous contact dermatitis (from topical agents) or infection

Evaluation: Clinical dx; severity of s/sx correlate w/ degree of venous incompetence; refer sx pts for duplex U/S to assess acute vs. remote DVT, reflux severity/site, as this guides tx options; venous reflux (>0.5 s of reverse flow) c/w diagnosis of venous insufficiency

General treatment: Walking, seated ankle flexion, leg elevation, stockings & massage to promote O₂ transport, prevent edema & progression to venous insufficiency

Compression stockings: Effective but poor compliance; avoid in pts w/ PAD and ABI <0.5; ↑ pressures work better; Class I: DVT ppx (10–18 mmHg), Class II: ↓ edema (20–30 mmHg); Contraindicated: severe PAD, acute cellulitis Skin care: Nonsoap cleansers, emollients, short course of topical corticosteroids Medications: Pentoxifylline + compression effective at ulcer healing; venoactive agents (e.g., escin & stanozolol ↓ sx)

Intervention: Consider vein ablation after 6 mo failed med Rx; ablation contraindicated in pregnancy, thrombosis, PAD, joint disease

Chemical ablation: Foam or liquid sclerosing agent → endothelial

 

damage/scarring; preferred for telangiectasias, reticular & small varicose veins; contraindicated if PFO

Thermal ablation: Laser delivers heat to veins; surface tx used for telangiectasias and reticular veins; endovenous lasers/RF probes used for saphenous vein Mechanical ablation: Vein ligation, stripping, phlebectomy

Other: Percutaneous iliac stenting, deep valve reconstruction

Patient information: AFP 2010;81:1003; JAMA 2012;308:2638;

2013;309:1306; vascularweb.org; vdf.org

LOWER-EXTREMITY ULCERS

 

Differential: Venous or arterial insufficiency, neuropathic (i.e., diabetic), pressure (i.e., decubitus), rheumatologic disease, malignancy, calciphylaxis, thromboembolism, Buerger disease, pyoderma gangrenosum, necrobiosis lipoidica, sickle cell

Workup: Assessment for osteomyelitis (i.e., wound probes to bone or has bone visible), infection (erythema, warmth, tenderness, swelling), screen for neuropathy (monofilament, tuning fork); ✓ pulses: If not palpable → ABI; segmental Doppler pressures & volume recordings once PAD diagnosed; duplex imaging, ESR/CRP, CTA/MRA, MRI for osteomyelitis as indicated; consider plain films for foreign body; biopsy ulcers present >3 mo to rule out malignancy

 

Clinical Features of Ulcers by Etiology
Ulcer Type	Arterial	Venous	Diabetic/Neuropathic
Location	Toes/heel/pressure points	Malleolar, lateral, posterior calf	Plantar region/bony prominences
Appearance	Irregular, pale/cyanotic	Irregular, pink base, exudative, shallow	Punched out, deep
Foot temp	Cold	Warm	Warm
Pain	+ (worse lying flat)	None/mild	–
Pulses	–	+	±

 

Veins	Collapsed	Varicosed	Dilated
Sensation	Variable	+	–
Deformities	–	–	+
Skin	Shiny, taut, pallor	Erythema, edema	Shiny, taut, doughy

(Adapted from AFP 2010;81:989; Ann Intern Med 2003;138:326; J Vasc Surg 2000;31:S1) Treatment (AFP 2010;81:989; Ann Int Med 2016;ITC18–1; Cochrane Database Syst Rev 2007;CD001733; JAMA 2005;293:217; NEJM 2004;351:48; Wound Rep Regen 2006;14:649):

Local therapy: Debridement of necrotic tissue (surgical vs. enzymatic); consider tetanus vaccination; daily self-inspection, elevation, avoid walking barefoot; smoking cessation; control HTN, HLD, DM2; keep wounds moist; wound care/podiatry/vascular referral for osteomyelitis prevention

Arterial: Anti-PLT medications; vascular specialist referral for revascularization; debridement should be performed after vascularization; consider hyperbaric O₂ if wound does not heal despite revascularization or if revascularization not possible

Venous: ASA; compression stockings (30→40 mmHg

(contraindicated if severe PAD) + pentoxifylline; worn indefinitely to prevent recurrence; abx only if infection present; elevation 30 min QID & o/n; skin grafting in chronic ulcers; ASA may help venous ulcer healing: abx not useful unless e/o systemic infection (↑ pain, ↑ redness, fever) Diabetic/neuropathic: Pressure off- loading w/ a contact cast/cast walker; ⊖ pressure therapy; revascularization of PAD; becaplermin gel (PLT-derived growth factor); consider tissue-engineered skin; role of hyperbaric O₂

unclear; prevention includes regular foot inspection, custom footwear, debridement of calluses, treating fungal infection, f/u q6mo for neuropathy, q1–3mo if hx ulcer; for ulcer; (see “Diabetic Foot Infection” subsection of “Skin & Soft Tissue Infection”); Amitriptyline, gabapentin, or pregabalin for neuropathic pain

Wound dressings: See “Wound Care”

 

 

SPORTS AND EXERCISE CLEARANCE

 

 

Background (AFP 2010;81:55; 2015; 92:371; JAMA 2003;289:2913; 2005;294:3011)

Exercise recommendations: 30 min of aerobic activity at least 5 d per week & preferably all days, or 25 min of vigorous physical activity 3×/wk AND moderate–high intensity muscle strengthening activity at least 2 d per week (∼50% of adults in US participate in regular physical activity)

(JAMA 2008;299:30)

Benefits of exercise: Pts w/ highest level of physical activity have 30– 40% ↓risk of CV disease vs. pts w/ lowest level, regardless of age, race, or gender (Circulation 2010;122:743); exercise ↓ risk of HTN, HLD, DM2, obesity, osteoporosis, stroke, depression, anxiety, & some cancers; inactivity → 5.3 million deaths annually worldwide (Lancet 2012;380:219) Risks of exercise: Risk of SCD in healthy pts is ∼1/1.51 million episodes of vigorous exertion (NEJM 2000;343:1355); ∼1/200,000 young athletes/y (Circulation 2007;115:1643), perhaps higher in college athletes

(Circulation 2011;123:1594)

Long-distance running: Cardiac arrest rate of 0.54/100,000 marathon & half-marathon participants, majority due to CAD or HOCM (NEJM 2012;366:130)

Types of exercise: Range in intensity, risk of collision (Adapted from Circ

2015;132:e326)

 

→ Increasing Static	High (>30%)	Bobsledding/ Luge Field events (throwing) Gymnastics Martial arts Rock climbing Sailing Water Skiing Weight Lifting Windsurfing	Body building Downhill skiing Skateboarding Snow boarding Wrestling	Boxing Canoeing Kayaking Cycling Decathlon Rowing Speed skating Triathlon
	Moderate (10–20%)	Archery Auto racing Diving Equestrian Motorcycling	American football Field events (jumping) Rodeoing Rugby Running (sprint) Surfing	Basketball Ice hockey Cross-country skiing Lacrosse Running (middle distance) Swimming

 

Component →			Synchronized swimming “Ultra” racing	Team handball Tennis
	Low (<10%)	Bowling Cricket Curling Golf Riflery Yoga	Baseball/softball Fencing Table Tennis Volleyball	Badminton Cross-country skiing (classic technique) Field Hockey Orienteering Race walking Racquetball/squash Running (long distance) Soccer
		Low (<50%)	Moderate (50– 75%)	High (>75%)
	→ Increasing Dynamic Component →

*High intensity dynamic exercise ↑ volume load on LV by ↑ HR and stroke volume (↑ EDV, ↓ ESV). High intensity static exercise ↑ pressure load on LV by ↑ ventricular arterial pressure and contractile state.

Common pathologies encountered with physical activity:

Young adults: HOCM (0.2% prevalence), coronary artery anomalies, aortic aneurysms, bicuspid AV, myocarditis, undiagnosed Marfan, congenital aortic/pulmonic stenosis; arrhythmias (long QT, Brugada, WPW) Older adults (>35 y): CAD → MI or ischemic arrhythmia

Exercise-induced bronchoconstriction: See “Asthma” (AFP 2011;84:427); asthma should be well controlled at rest and with exertion prior to clearance; rescue inhaler should be available Concussion: Immediate, reversible LOC after head trauma w/ brief period of amnesia (see “Concussion”) Commotio cordis: Blunt impact to chest (hockey puck, baseball, bodily collision) → V-Fib & SCD; prevent w/ chest protection, access to AEDs (NEJM 2010;362:917)

Evaluation (Circulation 2015;132:e256; NEJM 2003;349:1064)

Guidelines: ACC/AHA recommend 14-step hx/exam (below); ideally performed 6 wk prior to start of activity to allow for further testing

ECG: Adding ECG is cost-effective based on European data ($42,900/y of life saved), not known in US where prevalence of LQTS and ARVD is lower (Ann Intern Med 2010;152:276); European

 

Society of Cardiology & Olympic committee recommend ECG (Eur Heart J 2005;26:1422); adding ECG to H&P improves Se (99.8%) but ↓ Sp (false ⊕ rate 9.6%) (Heart 2011;97:1573); ACC/AHA suggests screening may be considered in small cohorts with close physician involvement, though mass screening is not recommended

History: Exercise hx, current peak activity level, hx heart disease, syncope, pulm disease, dyspnea, injuries, surgery, concussion; medications (incl OTC, herbal, supplements); illicits; screen for eating d/o; FHx of cardiac disease, arrhythmia, SCD

Exam: Major joints, scoliosis, Marfan features, cardiac exam (esp murmurs)

 

AHA 14-Step Preparticipation Screening of High-School & College Athletes
Personal History (Circulation 2007;11512: 1643; Circulation 2015; 132:e262)	(1) Exertional CP/discomfort; (2) Syncope or near syncope; (3) Excessive exertional or otherwise unexplained dyspnea/fatigue; (4) Hx heart murmur; (5) HTN (6) Prior restriction from sports (7) Prior testing of the heart
Family History	(8) Premature death related to heart disease or SCD; ask about drownings, car accidents, specific syndromes to ↑ recall; (9) Disability from heart disease in close relative <50 y; (10) Knowledge of FHx of hypertrophic/dilated CMP, ion channelopathy, long QT, Marfan, or arrhythmias
Physical Exam	(11) Murmur (listen supine & sitting, looking for signs of LVOT obstruction); (12) Femoral pulses to r/o aortic coarctation (13) Stigmata of Marfan; (14) Brachial artery BP (seated)
Contraindications for Sports Participation (AFP 2015;92:371)
•  Myocarditis or pericarditis •  Acute hepatomegaly or splenomegaly •  Untreated eating disorders •  Recent concussion (avoid contact sports) •  Severe, uncontrolled HTN •  Sickle cell dz (no high exertion, contact, or collision sports) •  Hemophilia or von Willebrand dz (contact sports)		•  Hypertrophic cardiomyopathy •  Long QT syndrome •  Poorly controlled convulsions (no dangerous activities) •  Recurrent burning UE pain/weakness until C-spine cleared •  Suspected CAD until fully evaluated •  Drug abuse

Cardiology referral: If abnl exam, FHx suspicious for SCD, or concerning factors found in 14-step exam; pt should not be cleared to participate prior to cardiology visit; recommendations for sports clearance & allowed sports for pts vary by condition (Am J Med

 

2012;125:742)

Documentation: Screening exam should be complete prior to signing any clearance paperwork (JAMA 2005;294:3011); document: “Pt is seen in consultation for exercise/sports clearance, & underwent the 14-step AHA preparticipation screening which revealed (no abnormalities) that would preclude participation in (sport); pt was counseled in preventative measures specific to sport, i.e., wearing a helmet.” HIPAA-compliant release necessary for provider to disclose info to party other than pt

Evaluation of Specific Populations (JACC 2015;66:2385; JAMA 2003;289:2913)

Previously inactive pts: Begin w/ short duration, moderate-intensity exercise & ↑ duration as tolerated; ETT prior to vigorous exercise program in pts w/ DM2 or cardiac risk factors (♂ >40 y, ♀ >55 w/ >2 CAD risk factors [see “Coronary Artery Disease”])

Chronically ill: As for previously inactive pts, unless: severe HTN, arrhythmias, uncontrolled metabolic dz, high-degree AV block, unstable angina, severe AS, recent ECG changes/cardiac event, acute myocarditis/pericarditis, or fall risk

Pts w/ cardiac disease (EF <50%, ischemia/arrhythmia w/ exercise,

>50% stenosis coronary artery): Cards eval prior to exercise (JACC 2005;45:1348); pts s/p MI or PCI can return to light exercise after 1 wk, sports after 4–6 wk, specific cardiac rehab program recommended; post-CABG pts may exercise after 4–6 wk if sternal wound is stable Mitral valve prolapse (MVP): No specific recommendations exist for pts with MVP and history of syncope, arrhythmia, personal or family history of SCD; if these issues exist, they should be thoroughly investigated independent of valvular disease (JACC 2006;48:e247); if MVP leads to severe mitral regurgitation, pt should be limited from at least some sports if evidence of LV enlargement or LVEF <60% Anticoagulation: Patients receiving therapeutic long-term anticoagulation should not engage in sports where impact is expected, e.g., ice hockey, American football

Sickle cell trait: Not justification to disqualify from competitive sports, however preventative strategies for acute events and prospective awareness of emergency medical strategies is recommended should one occur

Known predisposition to SCD, arrhythmia, Brugada syndrome,

 

myocarditis, HOCM, long-QT, Marfan, congenital heart disease: Detailed recommendations by ACC/AHA Scientific Statement (JACC 2015;66:2385); cardiology consultation advised

Counseling  (JAMA 2003;289:2913)

Moderate-intensity exercise defined as (1) Able to speak but not sing while exercising; (2) Maximum HR 65–75% of age-adjusted maximal HR (220-age) (AFP 2006;74:437)

Potential activities: Brisk walk (i.e., outside or in the mall during winter), yoga, tai chi, stair climbing, stationary bike, arm curls w/ wt every time there is a TV commercial, dancing, golf, tennis, vacuuming, jogging, calisthenics

 

5A’s of Provider Exercise Counseling

Assess: Eval pts current level of exercise/activity

Advise: Relate current health to activity benefit (i.e., exercise will help your BP)

Agree: Agree w/ pt if they are planning exercise plan & address barriers; set goals for duration, intensity of exercise

Assist: Help pt in developing strategies to achieve goals; involve nutrition, PT

Arrange f/u: Either appt or have someone from the office call to check how pt is doing & if there is anything that can be done to optimize care

Patient education: AFP 2006;74:2095;2097 (getting started w/ exercise); JAMA 2011;306:114 (concussion); JAMA 2005;294:3048 (fitness), shapeup.org

 

ADULT CONGENITAL HEART DISEASE

Background (Circulation 2008;118:2395; 2015;131:1884; NEJM 2000;342:256)

Epidemiology: Birth incidence ∼0.8%; significant ↑ in pediatric survival due to surgical and medical therapies have led to ↑ adult congenital heart disease (CHD) population; since 2000, prevalence adults

>children with CHD (Circulation 2007;115:163; Semin Thorac Cardiovasc Surg

2010;13:26), resulting in ↑ medical complexity, resource use (AJC 2016;118:906)

Etiology: Genetic (sporadic vs. syndromes w/ assoc cardiac abnl

 

[Down, Turner’s, Di George]); in utero exposures: ∼8–10%; maternal EtOH, infections (rubella), meds (dilantin, isotretinoin, thalidomide), metabolic synd (poorly controlled DM, PKU)

Noncyanotic CHD: BAV and VSD are most common CHD overall > ASD > coarctation (Circulation 2008;118:1768); in adults, ASD > VSD; many with CHD diagnosed as adults for the first time; if suspect ACHD, obtain history of exercise capacity, cardiac ROS, cyanosis (blue lips, fingers with exertion); h/o gestational exposures, growth and childhood sx, FHx

Cyanotic CHD: Most severe forms of CHD, including R → L shunts leading to hypoxia; most patients require palliative shunts in childhood to allow some flow to the lungs and development of pulmonary tree (shunt from subclavian artery, aorta, or SVC, IVC; see below); tetralogy of Fallot (TOF) most common cyanotic CHD in adults

Simple CHD: Bethesda classification (JACC 2001;37:1161): isolated congenital AV or MV disease (except parachute or cleft MV), isolated PFO/small ASD/small VSD; mild pulmonic stenosis; ligated or occluded ductus arteriosus; repaired secundum or sinus venosus ASD without other defects/shunts

Frequent complications in adulthood: Arrhythmias, heart block, sudden cardiac death, HF, pHTN, renal insufficiency, liver disease, and cirrhosis; many reversible if treated early

Evaluation

Detailed history crucial: Diagnoses, prior surgeries; 1 or 2 functional ventricles; presence of Eisenmenger syndrome (pulmonary pressures > systemic pressures); baseline BP and O₂ (many cyanotic pts have “normal” O₂ ∼ 80s at rest, 60s w/ exertion)

Exam: CV exam, JVP, surgical scars (sternotomy vs. thoracotomy), O₂ saturation, BP both arms; absent/weak pulse in one arm normal if prior Blalock–Taussig shunt

Workup: ECG (atrial vs. ventricular arrhythmias), CXR, labs

(NTproBNP ↑ at baseline in complex ACHD and “normal” ranges undefined; however ↑ above baseline assoc w/ HF and has prognostic value; obtain copies of prior records/outpatient physician

 

Diagnosis	Suggestive Features in   History, Exam	Suggestive ECG, Imaging
Atrial septal defect (ASD)	Unexplained TIA/CVA/ arterial emboli, atrial arrhythmias. ASD flow is silent (low gradient). May have wide fixed S2, loud P2, RV heave, PA tap. Look for ASD if unexplained RV overload	LAD in 15% primum ASD; RAD if large secundum or venosus ASD. Ectopic atrial rhythm in 15% sinus venosus ASD, 1st AVB if primum ASD
Ventricular septal defect (VSD)	Often murmur since childhood Holosystolic murmur; louder if smaller defect (higher gradient). Supracristal VSD may → aortic leaflet prolapse → AI murmur	RBBB; LAD/AVB if AV canal defect. LA + LV dilated if large shunt. RAD + RVH if pulmonary HTN
Bicuspid aortic valve	Soft aortic ejection click; AS or AI murmur. Check arm/leg BP for ?coarct	Assoc w/ ascending aortic aneurysms, coarctation
PDA	Continuous murmur	LV dilatation, dysfunction
Sub/supra-AS	Dyspnea, CP w/ exertion. FHx, AS murmur
Ebstein anomaly	Hx palpitations. PFO, secundum ASD common. TR murmur on exam	WPW in 25%, RA enlarged 1st AVB, RBBB
Transposition of great arteries	Progressive HF from failing RV. AV valve regurgitation. Prominent S2 (aortic valve closer to sternum)	Heart block (2% per year) Q-wave in Rt precordial leads (V1, V3R, inferior leads)

Management

Cardiology follow-up: All ACHD pts should have cardiologist; moderate–severe ACHD need regular follow-up with ACHD cardiologist (q6mo–1y depending on diagnosis); tertiary care follow-up assoc w/ more guideline-based care and improved outcomes (Circulation 2014;129:1804); all pts with moderate–severe ACHD should see ACHD cardiologist regularly

Prevention: Screen for atherosclerotic risk factors, including diabetes, metabolic synd, CAD are increasingly common, especially as pts often sedentary; encourage lifestyle changes, check cholesterol and treat per general guidelines; age-appropriate cancer screening (esp since life

 

expectancy continues to ↑)

Endocarditis prophylaxis: Per general guidelines (see “Infectious Diseases”)

Resources for patients: International Society for Adults with Congenital Heart Disease (isachd.org), Adults with Congenital Heart Disease Assoc (ACHA.org)