Correspondence

Hypertrophic Cardiomyopathy and Outflow Tract Obstruction

N Engl J Med 2003; 348:1815-1816May 1, 2003

Article

To the Editor:

In the article by Maron et al. (Jan. 23 issue)1 about the effect of left ventricular outflow tract obstruction on the clinical outcome in hypertrophic cardiomyopathy, the authors conclude that patients with obstructive hypertrophic cardiomyopathy have a higher risk of death from cardiovascular causes, stroke, or sudden death than do patients without obstruction. They also suggest that over a low threshold of 30 mm Hg, the magnitude of the gradient does not add any prognostic information. Does this mean that a patient with a gradient of 40 mm Hg has the same risk as a patient with a gradient at rest of 140 mm Hg? Should we apply the same criteria to indicate the need for myectomy or alcohol septal ablation in these two patients?

The authors say they cannot exclude the possibility that particularly marked degrees of obstruction may adversely affect the prognosis in certain patients. Why did they not analyze the risk for patients with very severe gradients (i.e., more than 90 or 100 mm Hg) in their study population?

Lorenzo Monserrat, M.D.
Juan Canalejo Hospital, 15006 A Coruña, Spain
lorenzo_monserrat@canalejo.org

Manuel Penas-Lado, M.D.
Hospital Provincial, 36071 Pontevedra, Spain

Alfonso Castro-Beiras, M.D.
Juan Canalejo Hospital, 15006 A Coruña, Spain

1 References

1
Maron MS, Olivotto I, Betocchi S, et al. Effect of left ventricular outflow tract obstruction on clinical outcome in hypertrophic cardiomyopathy. N Engl J Med 2003;348:295-303
Full Text | Web of Science | Medline

To the Editor:

Maron and colleagues have addressed one of the vital issues in hypertrophic cardiomyopathy — the effect of the outflow gradient on the long-term clinical outcome. However, they did not separately address the subgroup of patients with midcavitary obstruction, which should be discussed separately in any long-term observational study.1 The prevalence of midcavitary obstruction is estimated at 1 percent; however, it is known to vary considerably among different patient populations.

Khurshid Iqbal, M.D., D.M.
Nisar A. Tramboo, M.D., D.M.
Khalid Mohi-Ud-Din, M.D., D.M.
Sher-i-Kashmir Institute of Medical Sciences, 190011 Srinagar, India
khurshid@vsnl.com

1 References

1
Kuhn H, Mercier J, Kohler E, Frenzel H, Hort W, Loogen F. Differential diagnosis of hypertrophic cardiomyopathies: typical (subaortic) hypertrophic obstructive cardiomyopathy, atypical (mid-ventricular) hypertrophic obstructive cardiomyopathy and hypertrophic non-obstructive cardiomyopathy. Eur Heart J 1983;4:Suppl F:93-104
Web of Science | Medline

To the Editor:

I would like some clarification of seemingly contradictory data that Maron et al. presented in Table 1 of their article. This table lists deaths related to hypertrophic cardiomyopathy in the group of patients with outflow tract obstruction and in the group without obstruction (14 percent of patients with obstruction and 11 percent without obstruction, with sudden death in 7 percent and 6 percent, heart failure in 4 percent and 4 percent, and stroke in 3 percent and 1 percent, respectively) before the end of the study period. According to Table 1, there were no significant differences in these outcomes between the group with resting outflow obstruction and the group without obstruction. These results seem to be at odds with the data presented in Figures 1, 2, and 4, which show significant increases in each of these end points among patients with outflow obstruction at rest.

Daniel M. Spevack, M.D.
New York University School of Medicine, New York, NY 10016
danielspevack@yahoo.com

Author/Editor Response

Monserrat et al. note that at a level above 30 mm Hg, the magnitude of the left ventricular outflow tract gradient did not add prognostic information in our study population of patients with hypertrophic cardiomyopathy. When the relation between a greater magnitude of obstruction (≥30 mm Hg) and the end points of progression to severe symptoms and death from heart failure or stroke were analyzed, no significant differences were identifiable. This result probably reflects the dynamic nature of subaortic obstruction in hypertrophic cardiomyopathy, with even modest gradients at rest (30 to 50 mm Hg) representing a marker for the potential generation of much higher gradients with physical exertion (which are responsible for disabling symptoms).

However, we do not believe these data imply a sweeping alteration in management strategies for patients with severe symptoms that are refractory to drug therapy, in whom gradients of 50 mm Hg or more at rest or with provocation are required for major therapeutic interventions (surgical myectomy or alcohol septal ablation).1 Monserrat et al. pose the important question of whether the management considerations for a hypothetical patient with a modest resting gradient of 40 mm Hg (undoubtedly, >50 mm Hg with exertion) are the same as those for a patient with an extreme resting gradient of 140 mm Hg. On the basis of our data, major interventions are justified in both clinical circumstances. To determine whether patients with severe refractory symptoms and resting gradients of only 30 to 50 mm Hg are eligible for surgery or ablation, it is our practice to provoke obstruction with physiologic exercise (with the use of exercise echocardiography, not pharmacologic agents) to demonstrate that symptoms related to heart failure that are elicited during physical exertion are associated with inducible gradients of 50 mm Hg or more.

In response to Iqbal et al.: we did not separately analyze the extraordinarily small subgroup of patients with midcavitary obstruction in comparison with patients who had typical subaortic obstruction due to mitral-valve systolic anterior motion. Since both levels of obstruction may produce substantially increased left ventricular pressures, we have no reason to predict any significant differences in the clinical outcome between these subgroups.

Dr. Spevack suggests that Table 1 in our article, which shows no statistical difference in mortality between patients with obstruction and those without obstruction, is at odds with Figures 1, 2, and 4. We do not agree. The data in Table 1 do not represent legitimate statistical comparisons of the clinical outcome over time (substantiated by our use of the notation “NA,” for “not applicable”). Time-to-event (Kaplan–Meier) analyses of survival, the results of which are shown in Figures 1, 2, and 4, are the proper statistical method for demonstrating the relation between the outflow gradient and the clinical outcome over time in prospectively evaluated cohorts of patients.

Martin S. Maron, M.D.
Tufts–New England Medical Center, Boston, MA 02111

Iacopo Olivotto, M.D.
Ospedaliera di Careggi, 50132 Florence, Italy

Barry J. Maron, M.D.
Minneapolis Heart Institute Foundation, Minneapolis, MN 55407
hcm.maron@mhif.org

1 References