The New Natural History of Marfan’s Syndrome
Abstract & Commentary
Synopsis: Death due to cardiac structural complications is rare in young Marfan’s patients followed carefully on medical therapy, but arrhythmogenic sudden death occurs and is more common in those with LV dilatation.
Source: Yetman AT, et al. J Amer Coll Cardiol. 2003;41:329-332.
It is believed that sudden death in marfan’s syndrome is usually due to aortic dissection and rupture. The ubiquitous use of pharmacologic therapy to abrogate this complication and the routine use of echo- cardiography to detect dangerous levels of aortic dilatation raises the issue of the natural history of Marfan’s syndrome in the modern era. Thus, Yetman and colleagues retrospectively reviewed the experience at 1 institution with 70 consecutive Marfan’s patients followed in a special clinic for up to 24 years. The patients were seen biannually, and echocardiograms were done every 6-12 months. In addition, ambulatory ECG monitoring was performed initially off medication and subsequently if clinically indicated. Patients were divided into those with ventricular premature beats (VPBs) > 10 per hour and compared to those with < 10 VPBs/hr. The 70 patients, 34 men and 36 women, had a median age of 10 years (range, birth to 52 years) at diagnosis and 17 years (range, 1.5-55 years) at final follow-up. The median follow-up was 6 years (range, 20 months to 25 years). A family history of Marfan’s syndrome was present in 24 patients, and 13 of these had a family history of sudden death. Although all patients were started on blood pressure-lowering medications, 83% were still on such therapy at final follow-up due to adverse effects. Drug therapy was mainly beta blockers (37%) and angiotensin receptor blockers (26%) Six patients (8%) underwent aortic surgery; all but 1 were elective. None had valve surgery. All 3 deaths were sudden and none of these patients had structural failure at autopsy. Thus, all were believed to be arrhythmogenic. All patients had echocardiographic evidence of cardiovascular involvement: 90% aortic root dilatation, 68% left ventricular (LV) dilatation, and 11% LV systolic dysfunction. On ECG all were in sinus rhythm, 16% had prolonged QTc, and 60% had prominent u waves. On ambulatory ECG monitoring, 13 (21%) had > 10 VPBs and 4 had nonsustained ventricular tachycardia. Ventricular ectopy was univariately associated with mitral valve prolapse (100% of the 13 patients with VPBs), mitral regurgitation, LV dilatation, prolonged QTc, and u waves. Interestingly beta-blocker use was more common in the frequent VPB group. Multiple logistic regression analysis showed that only LV size was independently associated with frequent ventricular ectopy. All 3 of the deaths were in the frequent VPB group. Also, of the 4 patients with nonsustained VT, 2 died suddenly, and 2 were alive, 1 on amiodarone and 1 on beta blocker. Yetman et al concluded that death due to cardiac structural complications is rare in young Marfan’s patients followed carefully on medical therapy, but arrhythmogenic sudden death occurs and is more common in those with LV dilatation.
Comment by Michael H. Crawford, MD
Most cardiologists are well aware of the need to perform routine echocardiograms in Marfan’s patients to detect increasing aortic size. Also, we recognize that mitral valve prolapse and aortic regurgitation can be a problem in some patients. However, ventricular tachyarrhythmias have not been prominent in our thinking. This modern natural history study suggests that sudden death due to ventricular arrhythmia is now the most common cause of death in young Marfan’s patients. Although some of the patients in this study had aortic surgery (8%), none died of aortic rupture, and none had mitral valve surgery.
This study represents intensive management of these patients in 1 center. Patients were seen at 6-month intervals with echoes every 6-12 months and routine ambulatory ECG monitoring at the time of diagnosis and during follow-up as necessary. Pharmacologic antihypertensive therapy was liberally used with 83% remaining on it long term. Despite the use of ambulatory ECG monitoring, apparently antiarrhythmic drugs other than beta blockers were not given, and none of the patients were given implantable defibrillators. Given the results, this decision is being questioned by the investigators.
By multivariate analysis only, LV dilatation was independently associated with frequent ventricular ectopy. Unfortunately, the study population is too small to assess the role of beta blockers and ACEI to prevent LV dilatation, but clearly this needs to be studied in this population. Apparently LV dilatation is common in Marfan’s patients even in the absence of regurgitation. Perhaps all Marfan’s patients should be on ACEI. Beta blockers can improve LV function in heart failure and prevent ventricular tachyarrhythmias in patients with ischemic heart disease. However, these beneficial effects may not occur in Marfan’s patients. Beta blockers may play a role in preventing shear forces in the aorta leading to dilatation and dissection, so they should probably remain as desirable therapy. This study suggests that in addition to beta blockers and ACEI, consideration should be given to antiarrhythmia therapy in those with demonstrated ventricular arrhythmias and those with LV dilatation that does not respond to ACEI and beta-blocker therapy. The role of defibrillators in Marfan’s patients remains to be elucidated, but this study suggests that they should be considered in patients with nonsustained VT on monitoring.
Dr. Crawford is Professor of Medicine, Mayo Medical School; Consultant in Cardiovascular Diseases, and Director of Research, Mayo Clinic, Scottsdale, AZ.
Synopsis: Death due to cardiac structural complications is rare in young Marfans patients followed carefully on medical therapy, but arrhythmogenic sudden death occurs and is more common in those with LV dilatation.You have reached your article limit for the month. Subscribe now to access this article plus other member-only content.
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