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.

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.

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.

Doppler and echocardiographic features of normal and dysfunctioning bioprosthetic valves.

Echocardiographic and Doppler studies were performed on 183 clinically normal and 58 severely dysfunctioning bioprosthetic mitral, aortic and tricuspid valves. The valve dysfunction resulted from spontaneous cusp degeneration in 49 instances and from paravalvular regurgitation in 9. The pulsed Doppler study demonstrated regurgitant flow in 36 (92%) of 39 regurgitant valves and 8 (90%) of 9 paravalvular regurgitant valves. Diagnostic echocardiographic features were present in only 51 and 10% of the patients, respectively. Although the Doppler regurgitant jet was peripheral in seven of the nine patients with paravalvular regurgitation, it was not possible to differentiate these patients from those who had valve degeneration and cusp tear at the periphery of the valve ring. Eight patients presented with a musical holosystolic murmur of mitral insufficiency. In all eight there was a characteristic honking intonation on the audio signal and a striated shuddering appearance on the video Doppler signal. Ten stenotic mitral bioprosthetic valves (less than or equal to 1.1 cm2 valve orifice) were identified by Doppler study. Diagnostic echocardiographic features were present in only two of these patients. The Doppler-derived valve orifice dimension correlated well (r = 0.83) with cardiac catheterization values. Fourteen asymptomatic or minimally symptomatic patients had echocardiographically thickened mitral cusps (greater than or equal to 3 mm). These patients had a significantly (p less than 0.0001) smaller valve area as compared with normal control valves, and during 4 to 24 months of follow-up, five of these patients developed severe valve regurgitation or stenosis. Doppler ultrasound is more sensitive than echocardiography in diagnosing bioprosthetic valve stenosis and regurgitation.(ABSTRACT TRUNCATED AT 250 WORDS)

Smoking and cardiovascular disease.

Cigarette smoking is the most preventable cause of cardiovascular morbidity and mortality. Smoking has been associated with a two-to fourfold increased risk of coronary heart disease, a greater than 70% excess rate of death from coronary heart disease, and an elevated risk of sudden death. These risks are compounded in the presence of hypertension, hypercholesterolemia, glucose intolerance, and diabetes, all of which exhibit a synergistic effect with smoking. The relationship between smoking and the risk of peripheral vascular disease has also been well documented. Smokers account for approximately 70% of patients with atherosclerosis obliterans and virtually all those with thromboangiitis obliterans. An association between smoking and cerebrovascular disease remains a matter of debate, although a higher risk of stoke and stroke-related mortality has been observed in smokers than in nonsmokers. Smoking has also been implicated in the development of cor pulmonale, but a direct association with congestive heart failure has not been established. Nicotine and carbon monoxide appear to play major roles in the cardiovascular effects of smoking. Both components adversely alter the myocardial oxygen supply/demand ratio and have been shown to produce endothelial injury, leading to the development of atherosclerotic plaque. Adverse effects on the lipid profile have been noted as well, but the relationship between these changes and the risk of cardiovascular disease remains to be confirmed. Notably, smoking cessation results in a dramatic reduction in the risk of mortality from both coronary heart disease and stroke. In light of the fact that the incidence of smoking has declined primarily among educated sectors of the U.S. population, future efforts must focus on providing effective education, including smoking cessation techniques, to the less-educated groups.

Inadvertent malposition of a transvenous-inserted pacing lead in the left ventricular chamber.

In conclusion, we propose the following approach to prevent and manage lead malposition in the left ventricle: A 12-lead electrocardiogram in the paced mode and an anterior and lateral chest view should be thoroughly inspected shortly after pacemaker implantation. A definitive diagnosis of malposition can be established with these tests. Development of any neurologic symptoms should be attributed to the malpositioned lead until proved otherwise. In such patients, serious consideration should be given to transcatheter or surgical lead extraction after a period of anticoagulation. If this is not possible, chronic anticoagulation with warfarin must be initiated, achieving an international normalized ratio of > or = 2.5. Antiplatelet therapy alone may not confer adequate protection against future cerebral events. Furthermore, most patients with neurologic manifestations do not have echocardiographic evidence of thrombus on the lead. Conversely, presence of thrombus is highly associated with neurologic symptoms. Any intraarterial lead must be removed due to inevitable complications. Patients who have remained completely asymptomatic for > or = 3 years may be followed carefully with no therapy. For asymptomatic patients diagnosed before this time period, we recommend empiric therapy with antiplatelet agents or low-dose warfarin (international normalized ratio 1.5-2) with careful observation for symptoms.

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.

Cardiac troponin I and cardiac enzymes after electrophysiologic studies, ablations, and defibrillator implantations.

Diagnostic electrophysiologic studies and defibrillator implantations with subsequent test discharges from the defibrillator do not cause an elevation in cardiac troponin I levels. All patients with an ablation had an elevation in the cardiac troponin I levels.

Mitral valve aneurysm after infective endocarditis in the billowing mitral leaflet syndrome.

Mitral valve aneurysm is an uncommon complication of infective endocarditis. This report describes a patient with severe regurgitation due to perforations in a mitral aneurysm who required mitral valve replacement 9 years after a staphylococcal infection was superimposed on a billowing mitral leaflet. The unusual auscultatory signs and angiographic appearance could have led to diagnosis of the aneurysm.

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.

Mechanism of a musical systolic murmur caused by a degenerated porcine bioprosthetic valve.

The cause of a musical (cooing) murmur produced by a degenerated bioprosthetic valve in the mitral position was investigated. Spectral analysis of the murmur recorded at the chest wall at the site of the maximum palpable impulse showed virtually all sound in a narrow frequency band around the dominant frequency of 158 hertz. The same valve, surgically removed and mounted in the mitral position in a pulse duplicating system, produced an audible musical murmur detected by a phonocatheter in the atrial chamber. Nearly all of the sound-pressure occurred in a narrow band of frequency around 145 hertz. High speed motion pictures (500 frames/s) showed systolic flutter of a flail leaflet. The frequency of this leaflet flutter was 142 hertz. Hot film anemometry showed minimal turbulence, all located near the margin of the regurgitant leaflet. The intensity of the murmur was unrelated to the intensity of turbulence. A second degenerated bioprosthetic valve that produced in vivo a typical blowing holosystolic mitral regurgitant murmur produced in vitro a murmur with a broad range of frequencies (20 to 500 hertz). With this valve, the intensity of the murmur was related to the intensity of the turbulence. Motion pictures showed no leaflet flutter. Flutter of an insufficient valve leaflet causing uniform and periodic high frequency fluctuating pressures therefore appeared to be the cause of the musical quality of the systolic murmur in a degenerated bioprosthetic valve.

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.

Echocardiographic changes in the thickness of porcine valves with time.

To assess the ability of M-mode echocardiography to detect the incidence and frequency of porcine xenograft valve thickening, echocardiograms were obtained in 147 mitral and aortic porcine xenograft valves implanted in 131 patients. The patients were divided into an early group in whom the echocardiograms were performed within two months of valve replacement, and intermediate group studied two to 48 months after surgery, and a late group 48 months or longer after surgery. The porcine cusp echoes were visualized with proper gain settings, enlarged, and then recorded on a strip chart. The mean thickness of both the mitral and the aortic cusps was measured with the valve in the coapted position. The mean thickness of the porcine mitral valve increased from 1.23 +/- 0.12 in the early group to 2.3 mm +/- 0.19 in the late group (P less than .02). Aortic valve thickness increased from 0.91 mm +/- 0.07 in the early group to 2.1 mm +/- 0.37 (P less than .05) in the late group. A significant change in valve thickness was not observed in the intermediate group. In the late group of valves, 21/82 (27 percent) had a thickness greater than 3 mm. Nine of these valves (43 percent) have required replacement because of clinical dysfunction. Only 1.6 percent (1/61) of the valves in the late group with a thickness of less than 3 mm had or developed severe porcine valve insufficiency (P less than 0.001). In all ten instances, the echocardiographic assessment of valve thickness was validated on gross examination of the valve removed at surgery. This study indicates that the thickness of both mitral and aortic porcine valves can be measured by M-mode echocardiography. Valve thickness increases after 48 months and those valves with thickening of 3 mm or more are at a higher risk of developing clinical evidence of valve dysfunction.

Differences in the shape of the normal, cardiomyopathic, and volume overloaded human left ventricle.

A transformation from the normal elliptical shape of the left ventricle that may accompany various disease states and that may be indicative of myocardial remodeling, has not been completely addressed in part because of the need for a descriptor of shape that is independent of chamber size. Accordingly, the goal of this study was twofold: to derive dimensionless echocardiographic descriptors of left ventricle chamber shape that are independent of chamber volume and to use these descriptors to quantitatively compare the shape of left ventricles that were either of normal size (81 +/- 17 ml, 19 patients) or were enlarged secondary to idiopathic cardiomyopathy (194 +/- 61 ml, 46 patients) or chronic aortic or mitral valve incompetence (196 +/- 67 ml, 14 patients). Two-dimensional and M-mode determined descriptors of left ventricle shape based on its width, length, and area were found to be independent of left ventricle volume. These descriptors were significantly greater in cardiomyopathy compared with the normal or dilated left ventricle secondary to valvular incompetence, indicating that the left ventricle had become nearly spherical. A spherical shape of the left ventricle was not observed with valvular incompetence. The ability to classify a patient as having either a normal or a cardiomyopathic left ventricle by discriminant function analysis was enhanced when both left ventricle size and shape were considered. In a prospective study using discriminant function and fractional shortening, we found that patients with valvular incompetence could be classified as having either a normal discriminant function and fractional shortening, an abnormal discriminant function and normal fractional shortening, or an abnormal discriminant function and fractional shortening.(ABSTRACT TRUNCATED AT 250 WORDS)

Origin and clinical relevance of musical murmurs.

Although our observations are limited to studies performed on a degenerated bioprosthetic valve that produced a musical murmur, we believe that they can be applied to musical murmurs caused by abnormal natural valves. Several points regarding the characteristics of musical murmurs have been clarified. A musical murmur results from a uniform periodic vibration of a cardiac structure. A non-musical murmur results from turbulent blood flow which initiates random vibrations of adjacent structures. The broad spectrum of frequency of a non-musical murmur reflects the broad range of random fluctuations of blood velocity that characterizes turbulent blood flow. The frequency, amplitude, and time of occurrence during systole or diastole of a musical murmur are dependent upon the hemodynamics in the vicinity of the vibrating structure. Variability of all of these characteristics of the murmur, therefore, may be expected. Musical murmurs may have a purer tone at a site distal to the source than close to the source. This may reflect a superimposition of a broad spectrum of noise due to turbulence close to the valve. With distance from the valve, turbulence attenuates more than the sound-pressure fluctuations which are due to the uniform vibrations of the valve. A pure tone, uncontaminated by this broad spectrum of noise due to turbulence, therefore, is heard at some distance from the valve.

Myocardial infarction with an initially normal electrocardiogram--angiographic findings.

To analyze the paradox of acute myocardial infarction (AMI) with an initially normal electrocardiogram (ECG), we reviewed the records of 732 patients discharged with a final diagnosis of AMI over a 2-year period. Twenty-one patient were identified whose initial ECG was normal and who underwent coronary arteriography during the index hospitalization. According to the ECG evolution, three distinct groups were identified: Group 1: those who subsequently developed ST elevation or Q waves (n = 7), Group 2: those who developed ST depression or T-wave inversion (n = 8), and Group 3: those whose ECG remained normal ( n = 6). Peak creatine kinase (CK), timing of the first ECG change, life-threatening complications, and location of the infarct-related coronary lesion were recorded. Infarct-related coronary lesions were also classified into those in a major coronary trunk versus those in secondary branches. The incidence of AMI with a normal ECG was 3.7%. There was no difference in the frequency of coronary artery involvement in the groups studied: left anterior descending (33%), right coronary artery (38%), and circumflex (28%). All ECG changes developed within the first 48 h of hospitalization; 17 +/- 15 in Group 1, and 24 +/- 12 h in Group 2. All six patients who had a persistently normal ECG (Group 3) had lesions in branch vessels (p < 0.05 when compared with Group 1 plus Group 2). Patients who developed ST elevation or Q waves (Group 1) always had a major artery trunk involved (p < 0.05 when compared with Group 2 plus Group 3). Patients in Group 3 had less myocardial damage and fewer complications compared with the other two groups. Myocardial infarction with an initial normal ECG is uncommon and may result from involvement of any of the three coronary arteries. Electrocardiographic evolution usually occurs within the first 48 h of hospitalization. Patients whose ECGs remain normal appear to have culprit lesions in coronary branches, smaller infarctions, and fewer in-hospital complications.

Prevention of early postoperative renal dysfunction in cardiac transplantation.

Fifty six patients undergoing cardiac transplantation were immunosuppressed with a multi-drug induction regimen in which Cs administration was delayed postoperatively until satisfactory hemodynamics and renal function were achieved. The advantage of this approach is the absence of acute renal dysfunction in the early postoperative period. This immunosuppressive regimen was well tolerated and without significant detrimental effects on patient survival, graft rejection, or infection.

Bronchial arteriovenous malformation in a child with hemoptysis. A case report.

Pulmonary arteriovenous (AV) malformations occur sporadically and in the pediatric population are most commonly associated with hereditary hemorrhagic telangiectasia. Hemoptysis is an infrequent presentation in this age group. Pulmonary angiography is considered to be the definitive diagnostic modality. The authors describe an otherwise healthy eleven-year- old girl who presented with massive hemoptysis secondary to a large bronchial AV malformation unrelated to any congenital anomalies. The pulmonary angiogram appeared normal and the diagnosis was established by digital subtraction aortography. Successful embolotherapy was performed by selective injection of polyvinyl alcohol particles into the culprit bronchial artery.

Left ventricular-right atrial fistula following mitral valve replacement.

Acquired intracardiac shunt after prosthetic valve replacement is a rare complication, and reoperation for correction of this disorder carries a high mortality rate. We report such a case of left ventricular-right atrial fistula after mitral valve replacement in which the patient died of multiple complications. Awareness, prevention, and early diagnosis are, therefore, extremely important.