CardioExchange Archive

A previously healthy 26-year-old man is seen for evaluation of palpitations. He reports “skipped beats” since age 18, with occasional short runs of fast, strong beats that are precipitated by alcohol use and marked exertion. He denies associated symptoms such as syncope, chest pain, and shortness of breath.      

His medical history is unremarkable, and he takes no medications. He is currently a graduate student and an avid long-distance runner, having run several marathons. He denies tobacco and illicit drug use and drinks alcohol socially.

The young man has an extensive family history of cardiac disease related to lamin A/C deficiency. His father was the index patient, diagnosed as heterozygous for the mutation at age 54, following cardiac resynchronization therapy (CRT) upgrade of an implantable cardioverter-defibrillator (ICD). The father had been diagnosed with atrial fibrillation and high-degree atrioventricular block at age 46, requiring pacemaker placement. He experienced ventricular tachycardia (VT) at age 50, requiring ICD placement with the subsequent CRT upgrade at 54. Four of the father’s six siblings carry the lamin A/C deficiency: One suffered a sudden cardiac death, one had a heart transplant, two received ICDs, two received pacemakers, and three have undergone catheter ablation for atrial fibrillation. Average onset for cardiac involvement has been age 40.

The young patient’s baseline ECG shows sinus arrhythmia, a PR interval of 204 msec, low-voltage P waves, and right-axis deviation. An ambulatory ECG monitor showed multiple episodes of nonsustained VT.  

Genetic analysis reveals lamin A/C deficiency.

A transthoracic echocardiogram shows low-normal systolic function (LV ejection fraction, 53%) and high-normal LV size. Cardiac MRI shows significantly delayed enhancement in the mid myocardium of the basal to mid septum, and in the basal inferior and inferolateral walls.

Questions:

1. How would you manage this patient?

2. What are your considerations for device therapy (permanent pacemaker, ICD)?

3. Would you initiate pharmacologic therapy? If so, what drugs?

4. How would you advise the patient about participating in competitive sports, specifically long-distance running?

Response:

James Fang, MD

March 10, 2014

1. How would you manage this patient?

Patients with laminopathies (Disease Models & Mechanisms 2011; 4:562) are generally at risk for very rapidly progressive heart failure and premature sudden death (Circulation 2000; 101:473; J Am Coll Cardiol 2002; 39:981). There is often associated conduction-system disease and skeletal-muscle involvement (e.g., Emery-Dreifuss). Inheritance is usually autosomal dominant. Although this patient’s LVEF remains above 50%, his risk for arrhythmia is high (N Engl J Med 2006; 354:209).

2. What are your considerations for device therapy (permanent pacemaker, ICD)?

I would consider ICD therapy for primary prophylaxis despite the preserved LVEF because of the underlying disease, myocardial scarring, family history, and symptomatic nonsustained ventricular tachycardia (N Engl J Med 2006; 354:209).

3. Would you initiate pharmacologic therapy? If so, what drugs?

I would consider beta-blockers, although the recommendation is not based upon a substantial evidence base.

4. How would you advise the patient about participating in competitive sports, specifically long-distance running?

I would recommend against long distance running in general.

Follow-Up:

Anna Catino, MD

March 18, 2014

Thank you for the insightful responses. The patient underwent successful ICD implantation for primary prevention, given his MRI findings and NSVT on Holter monitor. Follow-up interrogation of the device has revealed short bursts of NSVT and atrial tachycardia, but the patient has not had any sustained arrhythmias. As you all note, it is unclear whether prophylactic use of ACE inhibitors or beta-blockers is beneficial prior to LV dysfunction, although some animal data suggest that carvedilol may delay LV dilation and dysfunction when introduced prophylactically (Circ Res 2010; 106:573). At this time, the patient has not started either therapy because he is concerned about side effects at his young age. He has been advised to limit participation in competitive sports but to continue moderate-intensity exercise.