A 45-year-old man presents to cardiology clinic to establish care. He has had several months of progressive dyspnea on exertion while playing basketball. He also reports intermittent palpitations for the last month. Two weeks ago, he passed out while playing and attributed this to exertion and dehydration. He denies smoking and alcohol intake.

Family history is significant for sudden cardiac death in his father at the age of 50 years. Autopsy has shown a thick heart, but he is unaware of the exact diagnosis. He has two children, ages 12 and 15 years old, who are healthy.

Vitals signs are blood pressure of 124/84 mmHg, heart rate of 70 bpm, and normal respiratory rate. On auscultation, a systolic murmur is present at the left lower sternal border. A 12-lead ECG showed normal sinus rhythm with signs of LVH and associated repolarization abnormalities. Echocardiography reveals normal LV chamber volume, preserved LVEF, asymmetric septal hypertrophy with wall thickness up to 16mm, systolic anterior motion of the anterior mitral valve leaflet with 2+ eccentric posteriorly directed MR, and resting LVOT gradient of 30mmHg which increases to 60mmHg on Valsalva.

You discuss your concern for an inherited cardiomyopathy, namely hypertrophic cardiomyopathy. In addition to medical management of his symptoms and referral to electrophysiology for ICD evaluation, which of the following is appropriate at this time?

A 

Order blood work for genetic testing

B 

Referral for genetic counseling

C 

Cardiac MRI

D 

Coronary angiogram

E 

All of the above

Explanation  

The correct answer is B – referral for genetic counseling. 

Several factors on clinical evaluation may indicate a possible underlying genetic cardiomyopathy. Clues may be found in:

·       Cardiac morphology – marked LV hypertrophy, LV noncompaction, RV thinning or fatty replacement on imaging or biopsy

·       12-lead ECG – abnormal high or low voltage or conduction, and repolarization, altered RV forces

·       Presence of arrhythmias – frequent NSVT or very frequent PVCs, sustained VT or VF, early onset AF, early onset conduction disease

·       Extracardiac features – skeletal myopathy, neuropathy, cutaneous stigmata, and other possible manifestations of specific syndromes

In select patients with nonischemic cardiomyopathy, referral for genetic counseling and testing is reasonable to identify conditions that could guide treatment for patients and family members (Class 2a, LOE B-NR). In first-degree relatives of selected patients with genetic or inherited cardiomyopathies, genetic screening and counseling are recommended to detect cardiac disease and prompt consideration of treatments to decrease HF progression and sudden death (Class 1, LOE B-NR).

No controlled studies have shown clinical benefits of genetic testing for cardiomyopathy, but genetic testing contributes to risk stratification and has implications for treatment, currently most often for decisions regarding defibrillators for primary prevention of sudden death and regarding exercise limitation for hypertrophic cardiomyopathy and the desmosomal variants. Consultation with a trained counselor before and after genetic testing helps patients to understand and weigh the implications of possible results for their

own lives and those of family members, including possible discrimination on the basis of genetic information. Unless shown to be free of the genetic variant(s) implicated in the proband, first-degree relatives of affected probands should undergo periodic screening with echocardiography and electrocardiography.

In this patient with likely hypertrophic cardiomyopathy, a family history of sudden cardiac death, recent unexplained syncope, and two children, a referral for genetic counseling is appropriate at this time. However, option A is incorrect because ordering genetic testing without meeting a trained counselor is not advised. 

Main Takeaway 

Patients with the possibility of genetic cardiomyopathies should be referred to trained genetic counselors before and after genetic testing to understand the implications of the testing and results.

Guideline Loc. 

Section 4.3, Table 7