Another condition with systolic anterior motion These conditions are met in another condition where systolic anterior motion and obstruction occurs. Certain patients after mitral annuloplasty for mitral regurgitation develop, as a complication, systolic anterior motion. Consequently surgical techniques have been developed to assure that the postoperative mitral coaptation point is posterior in the left ventricle, out of the way of ejection flow stream (24). An alternate technique uses a triangular anterior leaflet resection (25). Similarly, in HCM a new effective surgical technique addresses the problem of the mitral valve; the operation described by McIntosh reduces by plication the size of the anterior mitral leaflet, adding this procedure to traditional myectomy (26). Obstruction phase after mitral-septal contact After mitral-septal contact occurs a pressure gradient develops. The pressure gradient becomes the new hydrodynamic force on the obstructing mitral leaflet, pushing it further toward the septum (20). This, in turn, increases the pressure gradient which decreases the orifice further. An amplifying feedback loop is established in which obstruction begets further obstruction. This process is time-dependent; the longer in systole that it cycles the higher the final pressure gradient. The orifice narrows over time because of the rising pressure difference; the pressure difference rises over time because of the narrowing orifice. Progressive orifice narrowing explains why the peak of the continuous wave Doppler gradient occurs late in systole. Progressive narrowing also explains the concave contour of the continuous wave Doppler jet that is recorded in the LV outflow tract. This pattern of increasing acceleration is contrasted with that of aortic stenosis in figure 5. We believe that obstruction in HCM is best described as a flow drag triggered, time-dependent, amplifying feedback loop (20). Figure 5 Comparison of the Doppler velocity tracings of the high velocity jets of aortic stenosis and obstructive HCM. In aortic stenosis, as velocity increases acceleration decreases. In contrast, in obstructive HCM, as velocity increases, acceleration increases as well. In obstructive HCM, the rising pressure difference forces the mitral leaflet against the septum which decreases the orifice size and further increases the pressure difference. This amplifying feedback loop explains the concave contour seen in obstructive HCM (20). The orifice size changes as an inverse function of the pressure difference across the stenosis, with the pressure difference itself causing an increase in narrowing. In aortic stenosis this does not occur. Progressive orifice narrowing also explains why the jet peaks late in systole in obstructive HCM. Reprinted from Sherrid et al (8) by permission from the Journal of the American Society of Echocardiography 1997;10:707-12   1997 Mosby-Year Book Inc. Pharmacologic treatment Most symptomatic patients with obstructive hypertrophic cardiomyopathy can be managed successfully with medication (10). Patients are generally treated first with beta blockade. Unfortunately, this is often not effective in symptomatic patients with high resting gradients (27, 28). However, beta blockade does prevent the exercise related rise in gradient (27, 28). In addition, slowing heart rate improves filling in patients who have significant diastolic abnormalities. Verapamil was shown to lower gradients in an acute study after intravenous infusion (29). It has been shown to increase exercise tolerance (30). However, verapamil has been associated with as high as a 25% cardiac complication rate, including pulmonary edema and sudden death (31). This may occur because, in an individual patient, the vasodilating effects of verapamil may overshadow the negative inotropic effects. The high incidence of side effects was seen in a series of referral patients; side effects may not be as high in a less sick group of patients. Because of this we have used disopyramide for our patients who do not respond to beta blockade (32-34). Disopyramide is a potent negative inotrope. In normals, at rest, it has been shown to decrease echocardiographic left ventricular fractional shortening by 28% (35). It is quite effective in lowering outflow gradients, even in patients with high degrees of resting obstruction. The usual starting dose is 400-600 mg/day, using the controlled release preparation to allow twice a day dosing. Disopyramide levels can be monitored. Reduction in gradient has been observed with dosages and disopyramide levels lower than those needed for antiarrhythmic therapy (33). Exercise tolerance, as measured by treadmill time, is increased (34). Disopyramide dose can be limited by vagolytic side effects, dry mouth and exacerbation of prostatism. We have not observed proarrhythmia using disopyramide for obstructive HCM, nor has it been reported in the literature. Disopyramide can be used in combination with a beta blocker; beta blockade offers the advantage of slowing the exercise heart rate, and decreasing sympathetic mediated increase in gradient.   Rapid gradient elimination Gradients can vary spontaneously from day to day. A variety of circumstances of daily life have been shown to increase the gradient, including the post-prandial state, ethanol ingestion, erect posture and exercise. We routinely perform our echocardiographic studies after the patient has eaten. Doing so, we study the patient physiologically "at their worst"; this is useful when correlating symptoms of daily life with the echocardiogram. The process of finding the right drug to reduce outflow obstruction can be time consuming and frustrating for the symptomatic patient and the doctor alike. The physician seeks to give the smallest dose of drug(s) that works. So, drugs are generally introduced with gradually increasing dosage with echos performed after each dose change or with addition of a new drug. This strategy can not only result in prolonged hospital stays, repeated office visits and multiple echocardiograms, but it is also expensive. To facilitate rapid elimination of outflow obstruction we have evolved a system of acute drug testing with repeat echocardiograms on the same visit. Patients are treated using a clinical protocol of acute drug testing with the goal of rapid gradient elimination on sequential Doppler echocardiography (36). Intravenous metoprolol, to a dose of 15 mg is used first, unless contraindicated. If the Doppler gradient is reduced within 30 minutes to less than 30 mmHg, oral beta blockers are continued as sole therapy. If a > 30 mmHg gradient persisted, oral disopyramide is administered on the same day. We give disopyramide 250 mg as an oral loading dose and then repeat the echocardiogram 2 1/2 hours later (33). In patients with a contraindication to disopyramide, oral verapamil is begun 240-360 mg/day in divided doses (30). Treatment failures (defined as persistent gradient > 30 mmHg) are identified by Doppler within 48 hours and combination regimens are begun. PREVIOUS PAGE     NEXT PAGE