March 3rd, 2014
Case: Palpitations in a Young Runner with Lamin A/C Deficiency
Anna Catino, MD and James Fang, MD
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:
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:
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.
3 Responses to “Case: Palpitations in a Young Runner with Lamin A/C Deficiency”
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I would recommend a defibrillator, initiate medical therapy with a beta-blocker (and likely an ACEI to follow), and recommend against competitive sports.
The NEJM printed a letter to the editor (N Engl J Med 2006; 354:209-210 January 12, 2006) describing a short prospective series in which 19 individuals with lamin A/C deficiency with some conduction defect were implanted with defibrillators – over just about three years of follow-up, 8 of them received appropriate ICD therapy. The average EF was 58%.
While we can’t be confident whether medical therapy will reduce this patient’s risk of sudden death, it may reduce the risk of developing symptomatic CHF.
1. How would you manage this patient?
Since the patient has AVB, episodes of VT, family history and self confirmation of Lamin Def. I recommend a ICD implantation, participate in moderate exercise, carvedilol, avoid vigorous exercise and follow up for the possibility of cardiac transplant. Is controversial but I like to know the CK serum level.
2. What are your considerations for device therapy (permanent pacemaker, ICD)?
This kind of patients are in high risk to develop malignant arrhythmias when they develop conduction disturbances which grant a pacemaker even before they have HF.
3. Would you initiate pharmacologic therapy? If so, what drugs?
Yes, B blocker Carvedilol because the antioxidant properties.
4. How would you advise the patient about participating in competitive sports, specifically long-distance running?
Do not participate, but regular moderate exercise could be beneficial.
For the moment we don’t have a clear pathway for this patients, more investigation is need it and we have more questions than answers.
I completely agree with Dr. Fang. Cardiolaminopathies usually worsen progressively, the patient should start betablockers and I would also add ACE inhibitors and probably spironolactone too. I think that the ICD is needed both because of VT and because of the incipient conduction disease he shows. CMR showing cardiac fibrosis also support the need of the ICD in this context. Definitely he should not be involved in competitive sports of any kind.