Cardiology

Hypertrophic Cardiomyopathy: Management and Genetic Counseling

I. Hypertrophic Cardiomyopathy: What every physician needs to know.

Hypertrophic cardiomyopathy (HCM) is a genetic predisposition to left ventricular hypertrophy that is felt to most commonly arise from mutations in the genes encoding for cardiac sarcomere myofilaments. Classically, the hypertrophy is asymmetric, often involving primarily the ventricular septum, though any segment can be involved.

The hypertrophy can be evident at any age; however, most patients hypertrophy is detected after the onset of adolescence and, in some, may not be present until the fourth or fifth decade of life. The major pathophysiologic consequences include:

  • Dynamic left ventricular outflow tract obstruction (in up to 70% of cases)

  • Diastolic dysfunction

  • Increased risk of sudden cardiac arrest (approximately 1% annual event rate)

  • Intramyocardial fibrosis of variable degree

II. Diagnostic Confirmation: Are you sure your patient has Hypertrophic Cardiomyopathy?

The diagnosis of HCM is based on the demonstration, by cardiac imaging modalities (most commonly echocardiography, though CMR and Cardiac CT are perfectly viable), of left ventricular hypertrophy in the absence of other disease processes or conditions capable of resulting in the amount of hypertrophy present. There is no diagnostic test, including endomyocardial biopsy, that definitely confirms the diagnosis.

Other conditions that can result in increased left ventricular wall thickness include hypertension, chronic renal failure, glycogen storage diseases, Fabry disease, Freiderich's ataxia, amyloidosis, and physiologic adaptation to intense physical training. Clearly, several of these conditions would have extracardiac manifestations that should help cue the physician to the appropriate diagnosis. HCM typically has a greater degree of hypertrophy that is most commonly asymmetric, while the other conditions tend to concentric hypertrophy.

A. History Part I: Pattern Recognition:

Many HCM patients can lead normal or near-normal lifestyles with minimal symptoms. However, the most common symptomatic presentation is that of effort-related chest pain, dyspnea, or syncope/pre-syncope.

One of the hallmark features of this symptom complex, which at face value is similar to that of coronary artery disease or valvular aortic stenosis, is that the severity of the symptoms varies from day-to-day, or even within the same day. Patients have "good" days when they feel almost no limitation juxtaposed with days when activities of daily living are impacted. The presence of the symptoms that vary from day-to-day, in patients who do not fit the typical demographic profile of CAD or AS, should prompt consideration of HCM as the diagnosis.

B. History Part 2: Prevalence:

HCM is observed in approximately 1:500 individuals in populations around the globe.

C. History Part 3: Competing diagnoses that can mimic Hypertrophic Cardiomyopathy.

  • Hypertension—typically the LVH of hypertension is less severe and is concentric.

  • Chronic renal failure—LVH tends to be concentric and the renal failure is clinically manifest.

  • Glycogen storage diseases—more commonly observed in children.

  • Fabry disease—often associated with neurologic or renal effects; the LVH is more concentric and less severe than HCM.

  • Amyloid—LVH tends to be concentric; systemic disease can be apparent in some; specific imaging features can be helpful as can endomyocardial biopsy if cardiac amyloid is highly suspected

  • Athletic adaptation—LVH is less severe, is concentric, and there is associated borderline or mild LV cavity dilatation so that volume to mass ratio remains normal

D. Physical Examination Findings.

Key physical examination features include:

  • Normal carotid upstroke with possible bifid pulsation when there is outflow obstruction. The classical pulse contour is described as being "spike and dome" with the latter portion representing flow as the dynamic obstruction develops during ejection.

  • Abnormal apical pulsation

    • Sustained

    • Bifid

    • Trifid

  • Late peaking systolic ejection murmur at upper sternal border that increases in intensity with

    • Valsalva

    • Squat-to-stand

    • Exertion

    • Post-PVC

  • Mitral regurgitation murmur

  • Pulse pressure decreases after PVC (Brockenborough phenomenon)

E. What diagnostic tests should be performed?

  • Echocardiography

  • Resting 12-lead electrocardiogram

  • 24-hour ambulatory electrocardiogram

  • Exercise test

1. What laboratory studies (if any) should be ordered to help establish the diagnosis? How should the results be interpreted?

There are no specific laboratory tests that confirm HCM.

  • Serum protein electrophoresis can be useful to exclude conditions such as amyloidosis.

  • Genetic testing for HCM mutations is recommended for patients who want to use genetic analysis as the methodology to screen family members

  • Genetic testing for HCM mutations is recommended for atypical presentations of HCM.

  • Testing for Andersen-Fabry is recommended for atypical presentation, particularly if neurologic or nephrologic signs are present.

2. What imaging studies (if any) should be ordered to help establish the diagnosis? How should the results be interpreted?

  • Echocardiography is the primary imaging modality to establish the diagnosis and assess the pathophysiologic impact of HCM

  • Cardiac magnetic resonance imaging is recommended in the following situations:

    • Incomplete visualization by echocardiography

    • Suspicion of abnormal distribution of hypertrophy

    • Suspicion of apical aneurysm

    • Assessment of late gadolinium enhancement if SCD risk stratification is equivocal after assessment of standard risk markers

  • Exercise echocardiography can be useful for symptomatic patients in whom a resting gradient (>50 mmHg) was not found during resting echocardiography.

III. Management.

The management of HCM can be segmented into core counseling, family screening, assessment of risk of sudden cardiac death, and treatment of symptoms.

Core counseling

  • Patients should understand the prevalence of HCM as well as the fact that the majority of patients live a near-normal lifespan without advanced therapies but that for some patients significant symptoms and/or arrhythmias may occur.

  • Manage other diseases according to relevant guidelines

  • Participate in regular low-intensity physical activity as a part healthy lifestyle

  • Maintain hydration

  • Refrain from competitive athletics

Family screening

Screening of all first-degree relatives is recommended as HCM is generally recognized as an autosomal dominant condition.

  • Commencing at the onset of pubescence, participation in intense competitive athletics, or symptoms, whichever is earliest.

  • Either imaging or genetic testing can be used

    • If the patient chooses not to pursue genetic testing, or no clear HCM-associated mutation is identified, then screening with ECG andechocardiography is recommended.

      • Every 5 years for adult relatives not participating in athletics

      • Annually for athletes and adolescents

    • If a definitive HCM-associated mutations is identified, genetic screening becomes the preferred methodology

Sudden cardiac death risk assessment

The overall incidence of sudden cardiac death among HCM patients is approximately 1% per year. Several risk markers have been used to help identify HCM patients at higher than usual risk for whom an ICD may be recommended. All patients should have risk stratification at performed at initial evaluation and every 1 to 2 years thereafter.

The risk factors to be assessed include:

  • Personal history of cardiac arrest or sustained ventricular arrhythmia

  • Family history of sudden cardiac death in first-degree relatives

  • Maximum left ventricular wall thickness (high risk arbitrarily defined at greater than or equal to 30 mm)

  • Recent, unexplained syncope

  • Nonsustained ventricular tachycardia on a 24-hour ambulatory ECG

  • Hypotensive or flat blood pressure response to exercise

The decision to proceed with ICD placement is based on a personalized discussion with patient that includes a discussion of the risk for SCD as well as the complications of ICDs. Guidelines currently recommend:

Class I - Recommended

Personal history of cardiac arrest, sustained ventricular tachycardia, or ventricular fibrillation

Class IIa - Reasonable

Maximum left ventricular wall thickness equal to or greater than 30 mm

Recent, unexplained syncope

Family history of SCD in one or more first-degree relatives

Nonsustained ventricular tachycardia in the presence of other risk modifiers

Abnormal blood pressure in the presence of other risk modifiers

Class IIb - Uncertain

Isolated, nonsustained ventricular tachycardia

Isolated, abnormal blood pressure response to exercise

Management of symptoms

For patients with effort-related dyspnea, chest pain, or presyncope, pharmacologic management is the first line of therapy.

  • If possible avoid or eliminate pure vasodilators and high-dose diuretics

  • Beta-adrenergic blockade with goal resting HR 60-65 bpm, or verapamil

  • Disopyramide, added to beta-blockade or verapamil

Please note there are no proven benefits for these pharmacologic agents in asymptomatic patients.

If patients do not respond to pharmacologic therapy, or have intolerable side effects, then surgical myectomy or septal ablation are recommended as follows:

Class I - Recommended

Procedures should only be performed in centers with considerable experience with HCM and the procedures

Class IIa - Reasonable

Surgical myectomy is the standard therapy for most patients

Septal ablation is reasonable if there is prohibitive surgical risk

Class IIb - Uncertain

Septal ablation in the absence of increased surgical risk

A. Immediate management.

There is no empiric therapy with definitively proven efficacy for HCM.

B. Physical Examination Tips to Guide Management.

In the presence of exertional symptoms, a dynamic murmur that responds to maneuvers should prompt a thorough evaluation for resting or latent/provocable outflow tract obstruction.

  1. Standard transthoracic echocardiography with emphasis on identifying systolic anterior motion of the mitral valve, and documentation of peak instantaneous gradient.

  2. If gradient obtained in step 1 is <40 to 50 mmHg, then 2-D, color flow, and Doppler evaluation for gradient should be repeated during Valsalva maneuver

  3. If gradient obtained in step 2 is <40 to 50 mmHg, then consider an upright exercise test to determine if there is a gradient

  4. If exercise echocardiography is impractical or unhelpful, then consider invasive study with simultaneous echocardiography to elicit obstruction

C. Laboratory Tests to Monitor Response To, and Adjustments in, Management.

Genetic testing is available for HCM, although its primary role is to aid in screening relatives of known HCM patients. While phenotype-genotype correlations have been published, there are numerous and important deviations from those reported correlations. Additionally, the yield of genetic testing ranges from 40% to 60% and many identified variants of undetermined significance. Finally, the cost can be problematic for some patients.

D. Long-term management.

  • The success of pharmacologic therapy for obstructive HCM (Figure 1) is based on the status of the patient's symptoms.

  • The outflow tract obstruction varies significantly throughout the day and is not a reliable indicator of the efficacy of therapy

Figure 1

Suggested treatments for symptomatic obstructive HCM

E. Common Pitfalls and Side-Effects of Management

  • Most patients can be managed successfully with pharmacologic therapy

  • Avoidance of pure vasodilators and high-dose diuretics is important

  • If vasodilator therapy is required for comorbid conditions (e.g., hypertension), consider using them in conjunction with beta-blockers, or verapamil

  • In acute settings or postoperatively:

    • Avoid hypovolemia or hyperdynamic states

    • Avoid inotropic therapies

    • Avoid intraaortic balloon counterpulsation

IV. Management with Co-Morbidities

Hypertension can pose a difficult therapeutic challenge in HCM patients as many standard antihypertensives (e.g., dihydropyridine class calcium channel blockers, angiotensive converting enzyme inhibitors, angiotensin receptor blockers) can exacerbate the tendency to symptomatic left ventricular outflow tract obstruction.

If a patient's symptoms and hypertension cannot both be controlled simultaneously, then it is reasonable to consider definitive relief of outflow tract obstruction. Anecdotally, it has been observed that hypertension control can be more easily achieved after relief of the obstruction.

Sleep related breathing disorders may occur more commonly in HCM patients. Screening, and therapy when appropriate, is recommended. As coronary artery disease can increase the risk of complications in HCM, careful control of traditional cardiovascular risk factors is warranted.

Counseling

  • Family screening is recommended, as described, for all first-degree relatives.

  • Diet and exercise as part of a healthy lifestyle is advocated.

  • Pregnancy is generally well tolerated for HCM patients and it is reasonable to pursue vaginal delivery.

V. Patient Safety and Quality Measures

A. Appropriate Prophylaxis and Other Measures to Prevent Readmission.

N/A

B. What's the Evidence for specific management and treatment recommendations?

Gersh, BJ, Maron, BJ, Bonow, RO. "2011 ACCF/AHA guidelines for the diagnosis and treatment of hypertrophic cardiomyopathy". J Am Coll Cardiol. vol. 142. 2011. pp. e153-203.

Adelman, AG, Shah, PM, Gramiak, R, Wigle, ED. "Long-term propranolol therapy in muscular subaortic stenosis". Br Heart J. vol. 32. 1970. pp. 804-11.

Bonow, RO, Dilsizian, V, Rosing, DR, Maron, BJ, Bacharach, SL, Green, MV. "Verapamil-induced improvement in left ventricular diastolic filling and increased exercise tolerance in patients with hypertrophic cardiomyopathy: Short-and long-term effects". Circulation. vol. 72. 1985. pp. 853-64.

Sherrid, MV, Barac, I, McKenna, WJ. "Multicenter study of the efficacy and safety of disopyramide in obstructive hypertrophic cardiomyopathy". J Am Coll Cardiol. vol. 45. 2005. pp. 1251-58.

Woo, A, Williams, WG, Choi, R. "Clinical and echocardiographic determinants of long-term survival after surgical myectomy in obstructive hypertrophic cardiomyopathy[see comment]". Circulation. vol. 111. 2005. pp. 2033-41.

Ommen, SR, Maron, BJ, Olivotto, I. "Long-term effects of surgical septal myectomy on survival in patients with obstructive hypertrophic cardiomyopathy". J Am Coll Cardiol. vol. 46. 2005. pp. 470-76.

McLeod, CJ, Ommen, SR, Ackerman, MJ. "Surgical septal myectomy decreases the risk for appropriate implantable cardioverter defibrillator discharge in obstructive hypertrophic cardiomyopathy". Eur Heart J. vol. 28. 2007. pp. 2583-88.

Sorajja, P, Valeti, U, Nishimura, RA. "Outcome of alcohol septal ablation for obstructive hypertrophic cardiomyopathy". Circulation. vol. 118. 2008. pp. 131-9.

Cate, FJ, Soliman, OI, Michels, M. "Long-term outcome of alcohol septal ablation in patients with obstructive hypertrophic cardiomyopathy: a word of caution". Circ Heart Fail. vol. 3. 2010. pp. 362-9.

Ommen, SR, Gersh, BJ. "Sudden cardiac death risk in hypertrophic cardiomyopathy". Eur Heart J. vol. 30. 2009. pp. 2558-9.

C. DRG Codes and Expected Length of Stay.

2012 ICD-9-CM Diagnosis Code 425.1

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