Characterize Left Ventricular Outflow Obstruction in Hypertrophic Cardiomyopathy: DISCUSSION

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Importance of Hemodynamic Subsets

Classification of patients with HCM according to the nature and severity of LVOTO may have important therapeutic and prognostic implications. Patients with resting LVOTO manifest the most severe and frequent symptoms as well as the most profound hemodynamic systolic and diastolic abnormalities. Un­treated, this subset of patients has a poor prognosis, with one study reporting more than 50 percent to worsen symptomatically and 11 percent dying by four- year follow-up. For these reasons, aggressive therapy with Э-blockers, calcium antagonists, negative ino­tropic agents, and a lower threshold to performing septal myomectomy has been advised in this group of patients. Patients with nonobstructive HCM tend to have fewer symptoms, yet they may still demon­strate significant hemodynamic abnormalities related to the extent of left ventricular hypertrophy. Calcium antagonist therapy, which has primarily been advised in this group of patients, may provide symp­tomatic and hemodynamic improvement as well as result in regression of left ventricular hypertro­phy 1610,17 p_atients with latent LVOTO are usually the least symptomatic, with fewer atrial and ventricular arrhythmias, normal left ventricular end-diastolic pressures, and normal diastolic filling characteris­tics. Thus, blockers are considered agents of choice in treating this hemodynamic subset. Negative inotropic agents are believed to be contraindicated.

Echocardiography Characteristics of Subsets

Although this study made no attempt to reproduce the clinical, hemodynamic, or prognostic distinctions previously noted and summarized above, the echocar- diographic characteristics of the hemodynamic subsets noted in this study were similar to those previously described. Notably, patients with HCM with rest­ing LVOTO had the greatest amount of both septal and posterior wall hypertrophy and the greatest fre­quency and severity of systolic anterior movement of the mitral valve. Patients with latent LVOTO had less posterior wall hypertrophy than either those with resting LVOTO or those without LVOTO. Septal wall thickness, however, was increased in patients with latent LVOTO in comparison to patients without LVOTO. The frequency and severity of systolic anterior movement of the mitral valve in patients with latent LVOTO was intermediate to patients with resting LVOTO and those without LVOTO.
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Significance of Outflow Tract Gradients

Not only is the classification of patients according to the nature of LVOTO important, but so is an estimate of the severity of LVOTO. Although the controversy regarding the true pathologic significance of LVOTO persists, both “obstructionists” and “nonob- structionists” agree that elevated left ventricular pres­sures are detrimental to the left ventricle. There is good evidence to indicate that the degree of LVOTO relates to symptomatic status, and that improvement in symptoms resulting from either medical or surgical therapy is associated with concomitant decreases in the severity of LVOTO.

Although to our knowledge no previous study has characterized the distribution of hemodynamic sub­sets of patients with HCM using Doppler echocardi­ography, the data presented in this study are consistent with hemodynamic subsets identified previously by both clinical and invasive means. In a study by Rakowski et al, among 100 patients characterized clinically and hemodynamically by the nature of LVOTO, the distribution was such that 39 had resting LVOTO, 34 had latent LVOTO, and 27 had no obstruc­tion. Similarly, in 70 patients who were hemodyna­mically characterized by left ventricular manometry and transseptal left atrial catheterization, 39 percent had resting LVOTO, 40 percent had latent LVOTO, and 21 percent had no obstruction. In the current series we noted 43 percent with resting LVOTO, 30 percent with latent LVOTO, and 27 percent with no obstruction. Importantly, with the use of combined Doppler and echocardiography techniques, the diag­nosis of HCM can be established entirely by nonin­vasive means. This not only overcomes potential complications related to cardiac catheterization and transseptal puncture, but also is not complicated by concerns of artifactual gradients detected due to catheter entrapment.

Amyl Nitrite and Latent Obstruction

A variety of pharmacologic and physiologic maneu­vers may be employed to provoke latent LVOTO. Among those commonly used are the Valsalva maneu­ver, ventricular extrasystoles, and administration of sympathomimetic agents and Amyl. While induc­tion of extrasystoles and administration of sympatho­mimetics can be performed in the catheterization laboratory, they cannot be conveniently or safely used during routine echocardiography. The Valsalva maneu­ver, because it is difficult to perform, is frequently performed incorrectly and often results in loss of the Doppler signal due to chest wall movement; it has limited applicability in the evaluation of latent LVOTO. Amyl can be conveniently stored and administered. It has a rapid onset and offset of action, and during inhalation, continuous Doppler monitoring is possible so as to immediately detect any velocity changes.
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This study provides important information regard­ing normal values for left ventricular outflow tract velocities at rest and following inhalation of Amyl. The results for normal aortic outflow velocity are consistent with ranges reported by previous investigators. Amyl is a potent peripheral and coronary vasodilator that also acts to decrease venous return, resulting in a reflex tachycardia and a secondary inotropic re­sponse. By virtue of the inotropic, chronotropic, and vasodilatory effects of Amyl, an increase in cardiac output is observed. Previous studies in normal subjects indicate that while much of the increase in cardiac output is due to an increased heart rate, small increases in stroke volume also occur. This in addition to a decrease in left ventricular outflow dimension may account for the small but consistent increase in Dopp­ler peak left ventricular outflow velocity following Amyl inhalation in normal subjects. Thus, a physio­logically normal increase in Doppler velocity must be taken into account when identifying patients with provoked LVOTO.