Jeffrey B. Lakier

Comparative hemodynamic and neurohormonal effects of intravenous captopril and digoxin and their combinations in patients with severe heart failure

The effects of intravenous captopril and intravenous digoxin given separately and in combination on rest and exercise hemodynamics were studied in 16 patients with severe heart failure and sinus rhythm. When given separately, both captopril and digoxin decreased the pulmonary capillary wedge pressure by, respectively, 24% (p = 0.003) and 34% (p = 0.004) and systemic vascular resistance by 23% (p = 0.09) and 20% (p = 0.03). Only digoxin increased cardiac index by 23% (p = 0.03) and stroke work index by 52% (p = 0.01). During maximal exercise, captopril alone decreased systemic vascular resistance by 28% (p = 0.0002) and increased cardiac index by 33% (p = 0.02). Digoxin alone decreased pulmonary capillary wedge pressure by 11% (p = 0.04) and increased stroke work index by 44% (p = 0.01). The combination of captopril and digoxin resulted in a decrease in pulmonary capillary wedge pressure and systemic vascular resistance and an increase in cardiac index and stroke work index both at rest and during exercise that was greater than values observed with either drug given alone. Cardiac index response to the combination of captopril and digoxin correlated with baseline serum aldosterone concentration (r = 0.81, p less than 0.001) and plasma renin activity (r = 0.74, p less than 0.0002). A significant decrease in norepinephrine concentration was noted after digoxin was administered alone or added to captopril. These findings demonstrate that in patients with severe heart failure, the acute administration of captopril and digoxin has an independent salutary hemodynamic effect. The combination of these agents, however, has an adjunctive effect on cardiac function at rest and during exercise.

Frequency spectra of the first heart sound and of the aortic component of the second heart sound in patients with degenerated porcine bioprosthetic valves

To determine the usefulness of the frequency of heart sounds in the assessment of porcine bioprosthetic valve degeneration, frequency spectra of phonocardiograms of the first heart sound and the aortic component of the second sound were analyzed in 31 patients with degenerated porcine bioprosthetic valves. Comparisons were made with 35 control patients whose valves were inserted 1 month or less. Among 23 patients with degenerated porcine bioprosthetic valves in the mitral position, the dominant frequency of the first heart sound was 95 +/- 11 Hz, which exceeded the first sound in 18 controls (51 +/- 3 Hz) (p less than 0.01). The degenerated mitral porcine bioprosthetic valves of 14 patients showed calcification or fibrosis and the first heart sound in these patients was 115 +/- 16 Hz, which exceeded that of control subjects (p less than 0.001). The degenerated mitral porcine bioprosthetic valves of 9 patients showed torn leaflets only, and the first heart sound in these patients was 64 +/- 9 Hz, which did not differ from that of control subjects. In the aortic position, 8 valves were degenerated and the aortic component of the second sound was 109 +/- 12 Hz, which was higher than that in 17 control subjects (63 +/- 4 Hz) (p less than 0.001). Only 2 of these degenerated valves showed tears unaccompanied by calcific deposits or fibrosis, and the frequencies were comparable to that of control subjects. These observations indicate that the frequency of heart sounds in patients with degenerated porcine bioprosthetic valves becomes abnormally elevated when degeneration is accompanied by calcification or fibrosis, which causes the cusps to stiffen.

Idiopathic degeneration of the aortic valve: A common cause of isolated aortic regurgitation

To establish the etiology of isolated aortic valvular regurgitation, histologic examination was carried out on 27 consecutive surgically removed aortic valves from patients with aortic regurgitation. In 12 patients, the regurgitation was due to rheumatic or syphilitic valvular disease or a congenital bicuspid aortic valve. In the remaining 15, no etiology was apparent. In the latter group, seven aortic valves were identified by the surgeon as redundant and eight as thickened and retracted. Despite these gross differences, the histologic features of the 15 valves were similar and consisted of increased and disorganized elastic and collagen fibers, with variable quantities of acid mucopolysaccharide and calcium. Although small foci of myxomatous stroma were present, they did not differ substantially from those observed in age-matched competent aortic valves removed at necropsy, nor were they as extensive as described in reports of floppy aortic valves. Idiopathic degeneration was the most common cause of aortic regurgitation, occurring in more than half of the surgically treated patients. An underlying defect in the synthesis of collagen or elastic fibers, similar to that described in mitral valve prolapse, may be an important feature in aortic valve degeneration.

Echocardiographic evaluation of porcine bioprosthetic valves: experience with 309 normal and 59 dysfunctioning valves.

To determine the clinical value of echocardiographic evaluation of porcine bioprosthetic valves, the findings in all patients who had porcine bioprosthetic valve replacement and adequate quality echocardiographic studies from 1978 to 1982 were analyzed. The study includes 309 normal and 59 dysfunctioning valves. Valve dysfunction resulted from spontaneous cusp degeneration in 39 (34 valve regurgitations, 5 stenoses), infective endocarditis in 12, paravalvular regurgitation in 5, regurgitation of redundant cusps, mitral valve thrombi, and aortic stent stenosis in 3 others. Echocardiographic findings were correlated with gross surgical pathologic or autopsy findings in 45 of the 59 dysfunctioning valves. Echocardiographic abnormalities were demonstrated in 41 of 59 (69%) dysfunctioning valves. A systolic mitral or diastolic aortic valve flutter was diagnostic of a regurgitant valve caused by a torn or unsupported cusp margin and was observed in 28 of 34 (82%) regurgitant valves with no false-positive studies. Echocardiographic cusp thickness of greater than or equal to 3 mm correctly identified all regurgitant and stenotic valves with gross anatomic evidence of localized or generalized cusp thickening or calcific deposits. Echocardiographic valve abnormalities were observed in only 4 of 12 patients with infective endocarditis and in 1 of 5 with paravalvular regurgitation. Thus, echocardiography provides important information regarding the function of porcine bioprosthetic valves and is of value in the decision to replace these valves, especially when dysfunction is due to spontaneous cuspal degeneration. Echocardiography is neither sensitive nor specific in patients with infective endocarditis and paravalvular regurgitation.

Rationale and use of vasodilators in the management of congestive heart failure

Burch’s initial description of hexamethonium for the relief of intractable ventricular dysfunction’ was largely ignored until recently when a landslide of literary material has emerged proclaiming the effects of vasodilator therapy in the management of patients with congestive heart failure. Several comprehensive reviews of vasodilator therapy have been published.‘-” Nevertheless, a number of areas concerning this therapy remain clouded. In this presentation, we attempt to synthesize the results of numerous investigations and reviews into a form that may assist in the evaluation of this therapy.

Comparison of radionuclide and enzymatic estimate of infarct size in patients with acute myocardial infarction.

A comparison was made of the estimated size of the myocardial infarction occurring in 26 patients with a first infarction using creatine kinase (CK) enzyme release between radionuclide gated blood pool measurement of total and regional ventricular function and thallium-201 scintigraphic measurement of myocardial perfusion defects. Creatine kinase estimates of infarct size (enzymatic infarct size) correlated closely with the percent of abnormal contracting regions, left ventricular ejection fraction and thallium-201 estimates of percent of abnormal perfusion area (r = 0.78, 0.69 and 0.74, respectively, p less than 0.01). A close correlation also existed between percent abnormal perfusion area and percent of abnormal contracting regions (r = 0.81, p less than 0.01) and left ventricular ejection fraction (r = 0.69, p less than 0.01). Enzymatic infarct size was larger in anterior (116 +/- 37 CK-g-Eq) than inferior (52 +/- 29 CK-g-Eq) myocardial infarction (p less than 0.01) and was associated with significantly more left ventricular functional impairment as determined by left ventricular ejection fraction (33 +/- 7 versus 60 +/- 10%) (p less than 0.01) and percent abnormal perfusion area (58 +/- 14 versus 13 +/- 12) (p less than 0.01). No significant correlation was observed between enzymatic infarct size and right ventricular ejection fraction. These different methods of estimating infarct size correlated closely with each other in these patients with a first uncomplicated myocardial infarction.

Sequential radionuclide angiographic assessment of left and right ventricular performance and quantitative thallium-201 scintigraphy following acute myocardial infarction

Sequential changes in radionuclide angiographic measurement of left and right ventricular performance and quantitative thallium-201 scintigraphy were studied in 20 patients sustaining their first acute myocardial infarction (AMI). The studies were performed on the average 29.4 hours and 9.4 days after hospital admission. Anterior infarction had greater impairment of left ventricular (LV) performance in terms of ejection fraction and percentage of abnormal contraction area in addition to larger thallium-201 perfusion defects. At the time of the late study evidence of thallium-201 perfusion of infarcted area was seen in 14 of 20 patients, five of whom demonstrated improvement of regional wall motion. The remaining patients in the reperfused group and all of the patients in the nonperfused group failed to show evidence of LV functional improvement. This study indicates that reperfusion as measured by thallium-201 scintigraphy does occur spontaneously in 70% of patients with AMI and only in those patients with established reperfusion is there any potential for improvement in LV performance.

Hemodynamic determinants of the frequency and amplitude of a musical murmur produced by a regurgitant mitral bioprosthetic valve

The purpose of this study was to assess the hemodynamic determinant of the amplitude and frequency of a musical murmur produced by a regurgitant degenerated bioprosthetic valve in the mitral position. The prosthetic valve, obtained at surgery, was studied in the mitral position of an in vitro pulse duplicating system. In vitro, the valve produced a musical murmur that was caused by flutter of a flail leaflet. When the peak pressure difference between the left ventricle and left atrium was increased from 95 to 150 mm Hg, the fundamental frequency of the musical murmur increased from 91 to 187 hertz and the amplitude increased from 2,080 to 11,420 dynes/cm2. The fundamental frequency of the musical murmur was linearly related to the peak systolic pressure difference between the left ventricle and the left atrium (correlation coefficient [r] = 0.99). Similarly, the fundamental frequency of the musical murmur was linearly related to the magnitude of regurgitant flow across the valve (r = 0.99); and the regurgitant flow as expected was linearly related to the systolic pressure difference between the left ventricle and left atrium. The amplitude of the musical murmur was also related to both the peak systolic pressure difference between the left ventricle and left atrium (r = 0.99) and the magnitude of regurgitant flow (r = 0.99). These results indicate that the magnitude of regurgitant flow, determined by the systolic pressure difference between the left ventricle and left atrium, was a determinant of both the amplitude and the frequency of the musical murmur.

General anesthesia for intractable ventricular tachycardia

Abstract We report 2 patients who had recurrent life-threatening ventricular tachycardia (VT) unresponsive to usual medical management. Both patients had severe left ventricular dysfunction and were successfully treated by general anesthesia.