CARDIAC ABNORMALITIES
| UPDATE ON HYPERTROPHIC CARDIOMYOPATHY —Richard A. Lange, MD, Professor of Medicine, Johns
Hopkins University School of Medicine, and Chief of Clinical Cardiology, Johns Hopkins Hospital, Baltimore
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| Hypertrophic cardiomyopathy (HCM): definition—left ventricular (LV) hypertrophy in absence of identifiable
cause; LV wall thickness ≥15 mm; pattern—concentric (entire ventricle); apical (Yamaguchi’s disease); free wall;
septal (asymmetric septal hypertrophy; also called idiopathic hypertrophic subaortic stenosis, hypertrophic obstructive
cardiomyopathy; constitutes ≤25% of all HCM); incidence—1 in 500 adults
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| Asymmetric septal hypertrophy: septal bulging during diastole increases during systole; as blood injected into aorta,
anterior leaflet of mitral valved sucked into outflow tract, causing obstruction and systolic murmur; obstruction
and murmur increase—as LV chamber becomes smaller (eg, with volume depletion, Valsalva’s maneuver) or
contractility increases (eg, with exercise); obstruction and murmur decrease—as LV chamber enlarges (eg, volume
repletion, squatting maneuver)
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 | Outflow tract gradient: higher pressure in ventricle than aorta; increases with exercise; may be present at rest; severity
of gradient not associated with sudden cardiac death (SCD) or prognosis; gradient associated with development
of congestive heart failure (CHF)
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| Pathology of HCM: abnormality of muscle (myocyte disarray) and of vasculature (wall thickening of intramuscular
arterioles); patients may develop ischemia from small vessel disease; disorder of sarcomeric protein
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| “Athlete’s heart” vs HCM: intensive training, especially for endurance sports, associated with increased LV wall
thickness (always <16 mm) and cavity size; LV hypertrophy resolves when exercise stops; suspect HCM—if LV
wall enlarged (>14-15 mm in male patient; >12 mm in female patient), especially if LV cavity normal or small
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| Genetic aspects: abnormality of sarcomeric protein involved in contraction and relaxation (in 66%-75% of patients);
>150 mutations on ≥10 genes; autosomal dominant; incomplete penetrance; genotype-phenotype correlation undefined;
no role for genetic testing in HCM
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| Presentation: pulmonary congestion and dyspnea (90%); chest pain (75%); asymptomatic (10%-15%; diagnosed because,
eg, murmur detected, HCM in family); syncope (≈5%), due to arrhythmia (ventricular or atrial) or decreased
cardiac output; SCD (<5%)
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| Findings on evaluation: forceful point of maximal impulse (PMI); fourth heart sound (S4 ); bisferious pulse; pulmonary
vascular congestion; LV hypertrophy on electrocardiography (ECG); LV wall thickness on echocardiography
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| Natural history: symptoms usually stable or absent; symptoms increase with age; 10% to 15% of patients develop
CHF; SCD (annual incidence 1%-3%)
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| Sudden cardiac death: ≈33% of exercise-related SCD due to HCM (most during adolescence); major risk factors—
unexplained syncope; prior cardiac arrest; family history of SCD; sustained ventricular tachycardia (VT); nonsustained
VT (on Holter monitor); LV wall thickness ≥30 mm; abnormal blood pressure (BP) response during
exercise (BP falls); possible risk factors—atrial fibrillation (AF); ischemia; outflow tract obstruction; high-risk
genetic mutations; intense physical activity; risk factor impact—family history of SCD or syncope most significant
(quadruples risk); followed by wall thickness ≥30 mm, nonsustained VT, abnormal BP response; risk further
increased with ≥2 risk factors
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| Annual SCD risk stratification: history and physical examination; ask about syncope, family history; annual
echocardiography (LV wall thickness); Holter monitoring (for nonsustained VT); stress test (for abnormal BP response);
additional point—first-degree relatives need evaluation
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| Recreational sports: not applicable to patients at high risk (history of syncope, angina, surgery for HCM); avoid—
burst exertion (eg, basketball, tennis); adverse environmental conditions (eg, risk for volume depletion in extreme
heat); exercise programs focused on higher levels of achievement (competitive sports); intense isometric exercise;
extreme sports (eg, bungee jumping); permissible—bowling; golfing; brisk walking; skating; modest biking; hiking;
doubles tennis; swimming; treadmill; stationary bicycle; sports not requiring systematic training or pursuit of
excellence; encouraged—reasonable exercise
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| Medical therapy: obstructive HCM—to decrease contractility; β-blocker; calcium channel blocker, eg, verapamil;
disopyramide (Norpace; atrial stabilizing agent with negative inotropic properties); nonobstructive HCM—for pulmonary
congestion, diuretic (very low dose, carefully titrated); β-blocker; calcium channel blocker; “burned-out”
HCM—standard therapy for CHF
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| Other therapies: limited to patients with severe symptoms and high gradient; surgical myectomy (gold standard); alcohol
septal ablation; cardiac transplantation for nonobstructive HCM; automatic implantable cardioverter/defibrillator (AICD)
for patients at high risk for SCD (≥2 risk factors, ≥1 probably sufficient); myectomy—mortality risk <1% (in centers
where performed often and well); part of septum removed through aortotomy, removing outflow tract obstruction; alcohol
septal ablation—balloon catheter passed through septal artery; 100% alcohol injection causes infarction of
septal region; can almost eliminate gradient (in experienced centers); how procedures compare—myectomy
(slightly better gradient reduction; 40-yr follow-up; no septal scarring; invasive; low mortality) alcohol ablation (noninvasive;
limited follow-up; improves symptoms; creates scar at infarction [potential for ventricular arrhythmias];
techniques widely available)
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| Questions and answers: skeletal muscle involvement—not apparent in genetic abnormality; routine athletic
assessment—not cost-effective in absence of symptoms or family history; β-blockers and gradient—no dose-response
association between therapy and gradient; remember that gradient “doesn’t mean a whole lot”
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| ATRIAL FIBRILLATION: CURRENT APPROACHES TO TREATMENT —Gregory K. Feld, MD, Professor of
Medicine, and Director, Cardiac Electrophysiology Program, University of California, San Diego, School of Medicine
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| Epidemiology: AF disease of aging; present in ≈10% of population by seventh or eighth decade of life; ≤10 million
people in United States estimated to have AF; number grows with increase in elderly population
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| Definitions and mechanisms of AF
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| Paroxysmal AF: recurring and spontaneously converting AF; triggered by premature atrial contractions
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| Persistent AF: recurrent and sustained, requiring pharmacologic or electrical cardioversion; may be triggered by
premature atrial contractions but results from sustained reentry due to abnormal atrial tissue
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| Accepted (chronic) AF: term for persistent AF in patient treated for symptoms but not with cardioversion
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| Treatment issues: rate control vs rhythm control; anticoagulation and cardioversion; selection of antiarrhythmic
drugs; role of nonpharmacologic therapy (radiofrequency [RF] ablation; pacing; defibrillation)
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| Restoring sinus rhythm: potential benefits—ameliorate symptoms; preserve ventricular function; decrease stroke
risk; reduce mortality; actual benefits—reexamined in light of Atrial Fibrillation Follow-up Investigation of Rhythm
Management (AFFIRM) trial
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| Impact of AFFIRM trial: 5000 patients; 50% randomized to rate control with drugs and anticoagulation with warfarin
(Coumadin); 50% randomized to rhythm control with drugs and cardioversion; finding—mortality with
rhythm control slightly higher and associated with new arrhythmias, hospitalizations, and repeated cardioversion;
conclusion—rate control no worse than rhythm control; rhythm control may be worse (eg, proarrhythmic effects
of drugs); clinical practice—increased use of rate control to manage patients (when not symptomatic and successful
rhythm control unlikely)
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| Management of new-onset AF
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| Initial evaluation: for treatable underlying causes, eg, CHF, hyperthyroidism, uncontrolled hypertension
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| Hemodynamically unstable: cardioversion
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| Hemodynamically stable
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| <48 hr: rate control if needed; cardioversion
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| >48 hr: rate control if needed; anticoagulation for 3 to 4 wk; cardioversion
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| Early cardioversion: possible if transesophageal echocardiography [TEE] negative for thrombus
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| After cardioversion: anticoagulation for 4 to 12 wk
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| During anticoagulation: maintain normalized international ratio [INR] of 2 to 3; if <2, higher risk for stroke; if
>3, higher risk for intracranial hemorrhage
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| Continuing anticoagulation (4-12 wk following cardioversion): guidelines from American Heart Association and
American College of Cardiology
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| Persistent or accepted AF: <65 yr of age—if no risk factors (hypertension; CHF; history of stroke), aspirin or
nothing; if risk factor present, warfarin; >65 yr of age—warfarin; age not contraindication, unless indicated
by history, eg, falls, coagulation problem
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| After single episode: anticoagulation not warranted without evidence of recurrence
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| Pharmacologic rate control: calcium channel blocker or β-blocker, or both; if ineffective, add digoxin (not first-line
because exercise overcomes benefits)
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| Pharmacologic rhythm control: initiated when AF recurs during rate control therapy; patients without structural
heart disease—class I drugs; class IA (vagally mediated AF; disopyramide); class IC (flecainide; propafenone
[Rythmol]); patients with CHF or coronary artery disease (CAD)—class III drugs; amiodarone (drug of choice in
CHF; several risk factors, eg, liver toxicity, pulmonary toxicity; eventually require discontinuation in 15%-20% of
patients); dofetilide (may be used in CHF; follow algorithm for dosing); sotalol (avoid in severe CHF); high relapse
rate—study found ≈50% at 6 mo, ≤60% at ≈1 yr; amiodarone exception (≈65% effective); therapy for paroxysmal
AF—taking 225 mg of flecainide (followed by antiarrhythmic drug) converts acute episode of AF in 90% of patients
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| Nonpharmacologic therapy: ablation (with pacing) or modification of atrioventricular (AV) node (alleviates 90% of
symptoms); pacing therapy; defibrillator therapy; RF ablation for paroxysmal AF
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| Consequences of rapid ventricular rate: development of CHF and dilated cardiomyopathy; controlling AF shown to
correct ventricular dysfunction
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| AV node procedures: while ablation or modification of AV node significantly improves ventricular function and
quality-of-life scores, patients report exercise tolerance ≤20% less than normal; modification less expensive than
implanting pacemaker but effective ≤60% of time; if modification ineffective, speaker ablates AV node and implants
pacemaker (possible in same procedure)
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| Atrial pacing and defibrillation: atrial pacing effective only in sick sinus syndrome; defibrillation of atrium painful,
but accepted by some patients; with onset of AF, patient activates remote control device for cardioversion and
defibrillation; study of implantable cardioverter/defibrillator (ICD) found 86% efficacy, but antiarrhythmic therapy
required; premature beats set off new episode of AF
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| New procedure: designed to cure AF by eliminating underlying triggers located in pulmonary veins; placing catheters
and electrodes enables detection and ablation of source in muscle within pulmonary vein; results—paroxysmal
AF cure rate (80%-95%; may require repeat procedures); persistent or accepted AF cure rate (≈70%); complication
rate (1%-2%)
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| Questions and answers: persistent vs paroxysmal AF—event monitoring device for differential diagnosis; patient
may be hospitalized if heart failure or syncope present; initial management—rate control for patient presenting in
emergency department with symptoms and high ventricular rate; consequently, many patients spontaneously convert
to sinus rhythm; if not, patients admitted and given pharmacologic antiarrhythmic therapy (options include IV
ibutilide; efficacy ≈40%; involves risks); cardioversion remains option; atrial flutter—treatment not necessary if
asymptomatic; otherwise, ablation of flutter improves AF; when anticoagulation contraindicated—elevated risk
of stroke unavoidable; available therapy (aspirin; clopidogrel [Plavix]); role of heparin—may be added after myocardial
infarction; mechanism of action different from that of warfarin
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Educational Objectives
| The goal of this program is to educate internists about contemporary concepts of hypertrophic cardiomyopathy
(HCM) and atrial fibrillation (AF). After hearing and assimilating this program, the clinician will be better able to:
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| 1. Diagnose HCM.
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| 2. Counsel patients on genetic, exercise-related, and prognostic aspects of HCM.
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| 3. Evaluate and manage patients with new-onset AF.
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| 4. Manage pharmacologic therapies in patients with AF, including rate-control, rhythm-control, and anticoagulation.
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| 5. Advise patients on nonpharmacologic therapies for AF, including atrioventricular (AV) node procedures,
defibrillator therapy, and ablation of underlying triggers for AF.
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Discussed on This Program
Amiodarone HCl [Cordarone, Pacerone]
Aspirin (acetylsalicylic acid; ASA) [several trade names]
Clopidogrel bisulfate [Plavix] Disopyramide [Norpace, Norpace CR]
Dofetilide [Tikosyn] Flecainide acetate [Tambocor]
Propafenone HCl [Rythmol]
Sotalol HCl [Betapace, Betapace AF]
Verapamil HCl [Calan, Calan SR, Covera-HS, Isoptin SR, Verelan, Verelan PM] Warfarin sodium [Coumadin]
Suggested Reading
Abbas AE et al: Alcohol septal ablation for hypertrophic obstructive cardiomyopathy. J Interv Cardiol 18:155, 2005;
Dimitrow PP et al: The non-invasive documentation of coronary microcirculation impairment: role of transthoracic
echocardiography. Cardiovasc Ultrasound 3:18, 2005; Feld GK: Catheter ablation of atrial fibrillation: what is the
best technique for achieving a high cure rate with acceptable risk?. J Am Coll Cardiol 43:2054, 2004; Feld GK: Evolution
of diagnostic and interventional cardiac electrophysiology: a brief historical review. Am J Cardiol 84:115R,
1999; Feld GK: New approaches for the management of atrial fibrillation: role of ablation of atrial flutter. J Cardiovasc
Electrophysiol 10:1188, 1999; Feld GK: Radiofrequency ablation of atrial flutter using large-tip electrode catheters.
J Cardiovasc Electrophysiol 15:S18, 2004; Feld GK: Radiofrequency catheter ablation versus modification of
the AV node for control of rapid ventricular response in atrial fibrillation. J Cardiovasc Electrophysiol 6:217, 1995;
Garg A et al: Atrial Flutter. Curr Treat Options Cardiovasc Med 3:277, 2001; Klein GJ et al: Primary prophylaxis of
sudden death in hypertrophic cardiomyopathy, arrhythmogenic right ventricular cardiomyopathy, and dilated cardiomyopathy.
J Cardiovasc Electrophysiol 16 Suppl 1:S28, 2005; Matsumoto AY et al: Relationships among exercise
capacity, hypertrophy, and left ventricular diastolic function in nonobstructive hypertrophic cardiomyopathy. Am
Heart J 150:144, 2005; Minakata K et al: Mechanisms for recurrent left ventricular outflow tract obstruction after
septal myectomy for obstructive hypertrophic cardiomyopathy. Ann Thorac Surg 80:851, 2005; Murphy RT et al:
Genetics and cardiomyopathy: where are we now?. Cleve Clin J Med 72:465, 2005; Olivotto I et al: Gender-related
differences in the clinical presentation and outcome of hypertrophic cardiomyopathy. J Am Coll Cardiol 46:480,
2005; Olshansky B et al: The Atrial Fibrillation Follow-up Investigation of Rhythm Management (AFFIRM) study:
approaches to control rate in atrial fibrillation. J Am Coll Cardiol 43:1201, 2004; Roberts R et al: Current concepts
of the pathogenesis and treatment of hypertrophic cardiomyopathy. Circulation 112:293, 2005; Santini M et al:
Atrial fibrillation and heart failure. Europace 5 Suppl 1:S55, 2004; Soni A et al: Sudden death in nondilated cardiomyopathies:
pathophysiology and prevention. Curr Heart Fail Rep 2:118, 2005; Thaman R et al: Reversal of Inappropriate
Peripheral Vascular Responses in Hypertrophic Cardiomyopathy. J Am Coll Cardiol 46:883, 2005;
Watkins H et al: The prognostic impact of septal myectomy in obstructive hypertrophic cardiomyopathy. J Am Coll
Cardiol 46:477, 2005.
Faculty Disclosure
In adherence to ACCME guidelines, the Audio-Digest Foundation requests all lecturers to disclose any significant financial
relationship with the manufacturer or provider of any commercial product or service discussed. For this issue,
the faculty reported nothing to disclose.
Dr. Lange was recorded at 50th Annual Topics in Clinical Medicine, sponsored by Johns Hopkins University School
of Medicine, May 2-6, 2005, in Baltimore; Dr. Feld, at Topics and Advances in Internal Medicine, sponsored by the
University of California, San Diego, School of Medicine, March 3-9, 2005, in San Diego. The Audio-Digest Foundation
thanks the speakers and the sponsors for their cooperation in the production of this program.
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