Beneficial effects of pentoxifylline in patients with idiopathic dilated cardiomyopathy treated with angiotensin-converting enzyme inhibitors and carvedilol: results of a randomized study.

BACKGROUND: We previously reported beneficial effects of pentoxifylline, a xanthine-derived agent known to inhibit the production of tumor necrosis factor-alpha, in patients with idiopathic dilated cardiomyopathy treated with diuretics, digoxin, and ACE inhibitors. Since then, 3 large clinical trials showed important clinical benefits of beta-blockers in this population. Therefore, we designed the present study to establish whether in patients with heart failure already receiving treatment with ACE inhibitors and beta-blockers, the addition of pentoxifylline would have an additive beneficial effect. METHODS AND RESULTS: In a single-center, prospective, double-blind, randomized, placebo-controlled study, 39 patients with idiopathic dilated cardiomyopathy were randomized to pentoxifylline 400 mg TID (n=20) or placebo (n=19) if they had a left ventricular ejection fraction <40% after 3 months of therapy with digoxin, ACE inhibitors, and carvedilol. Primary end points were New York Heart Association functional class, exercise tolerance, and left ventricular function. Patients were followed up for 6 months. Five patients died (3 in the placebo group). Patients treated with pentoxifylline had a significant improvement in functional class compared with the placebo group (P:=0.01), with an increment in exercise time from 9.5+/-5 to 12.3+/-6 minutes (P:=0.1). Left ventricular ejection fraction improved from 24+/-9% to 31+/-13%, P:=0.03, in the treatment group. CONCLUSIONS: In patients with idiopathic dilated cardiomyopathy, the addition of pentoxifylline to treatment with digoxin, ACE inhibitors, and carvedilol is associated with a significant improvement in symptoms and left ventricular function.

Evidence against a myocardial factor as the cause of left ventricular dilation in active rheumatic carditis.

OBJECTIVES: The aim of this study was to determine whether left ventricular dilation and congestive heart failure in patients with acute rheumatic fever with carditis are accompanied by left ventricular contractile dysfunction. BACKGROUND: Acute rheumatic fever with carditis involves both the myocardium and endocardium, with consequent valvular regurgitation. The relative contribution of volume overload induced by valvular regurgitation and myocardial dysfunction due to rheumatic myocarditis to the overall degree of left ventricular dilation and congestive heart failure in these patients is unknown. METHODS: To investigate this, we evaluated 32 patients (15 male, 17 female, mean age 14 +/- 3 years) with documented active carditis and congestive heart failure. All 32 patients were found to have significant isolated mitral regurgitation or combined mitral and aortic regurgitation. Echocardiographic analysis of left ventricular dimensions and systolic performance was performed before and after isolated mitral or combined mitral and aortic valve replacement and the results were compared with those in 19 control subjects matched for age, gender and body surface area. RESULTS: Both preoperative left ventricular end-diastolic diameter and percent fractional shortening were significantly increased in patients compared with control subjects (57 +/- 7 vs. 43 +/- 3 mm, p < 0.001, and 38 +/- 6% vs. 33 +/- 1%, p < 0.001, respectively). After valve replacement, left ventricular end-diastolic diameter decreased significantly (57 +/- 7 to 47 +/- 6 mm, p < 0.001). Although percent fractional shortening decreased significantly postoperatively (38 +/- 6% to 32 +/- 6%, p < 0.001), the postoperative percent fractional shortening did not differ from that in control subjects (32 +/- 6% vs. 33 +/- 1%, p = NS). CONCLUSIONS: The results of this study indicate that left ventricular dilation and heart failure in patients with acute rheumatic carditis rarely occur in the absence of hemodynamically significant regurgitant valve lesions. Furthermore, rapid reduction in left ventricular dimensions and preservation of fractional shortening after isolated mitral or combined mitral and aortic valve replacement suggest that rheumatic carditis is not accompanied by any significant degree of myocardial contractile dysfunction.

Effect of abrupt mitral regurgitation after balloon valvuloplasty on myocardial load and performance.

The concept that mitral regurgitation masks myocardial dysfunction by reducing afterload and augmenting ejection performance has not been well established in humans. The effect of abruptly produced mitral regurgitation on left ventricular loading and performance was therefore evaluated in five patients who developed this complication after an otherwise successful percutaneous balloon mitral valvuloplasty. Mitral valve area by Gorlin formula calculated with forward flow increased from 0.92 +/- 0.14 to 2.75 +/- 0.82 cm2. Mean left atrial pressure did not decrease (19 +/- 4 to 19 +/- 6 mm Hg). The size of the left atrial V wave relative to mean left atrial pressure (peak V - mean left atrial pressure) increased from 7 +/- 4 to 19 +/- 6 mm Hg. Angiographic mitral regurgitation increased from 0+ or 1+ to greater than 3+ in each patient and regurgitant fraction increased from 0.23 +/- 0.11 to 0.55 +/- 0.09 (p less than 0.01). End-diastolic volume increased modestly from 148 +/- 15 to 159 +/- 15 ml (p = NS). Heart rate increased from 54 +/- 5 to 71 +/- 8 beats/min (p less than 0.05), which may have prevented further increases in preload by shortening the filling period. End-systolic stress decreased by 32% from 277 +/- 34 to 188 +/- 52 kdyn/cm2 (p less than 0.01) as a result of a 25% decrease in end-systolic pressure from 121 +/- 8 to 91 +/- 7 mm Hg and a 16% decrease in end-systolic volume from 67 +/- 13 to 56 +/- 8 ml (p = NS).(ABSTRACT TRUNCATED AT 250 WORDS)

Excessive vasoconstriction in rheumatic mitral stenosis with modestly reduced ejection fraction.

OBJECTIVES: The primary hypothesis examined was that underfilling due to inflow obstruction accounts for modestly depressed ejection performance in mitral stenosis. Having found little evidence to support this hypothesis, we sought to determine other factors that might differentiate patients with different levels of ejection performance. METHODS: Ventricular load and performance were compared in two groups of patients before and immediately after successful balloon valvuloplasty that was not complicated by mitral regurgitation: those in whom prevalvuloplasty ejection fraction was > or = 0.55 (group I, n = 10) and those in whom it was < 0.55 (group II, n = 11). RESULTS: Before valvuloplasty, mitral valve area was less in group II (0.65 cm2) than in group I (0.84 cm2, p = 0.02), but end-diastolic pressure (12 vs. 12 mm Hg in group I), end-diastolic wall stress (46 vs. 44 kdynes/cm2 in group I) and end-diastolic volume (152 vs. 150 ml in group I) were not less in group II, nor were these variables significantly reduced compared with those of a normal control group. In group II, end-systolic volume was larger (77 vs. 55 ml in group I, p = 0.001) and cardiac output was less (3.1 vs. 3.6 liters/min in group I, p = 0.03), possibly owing to higher systemic vascular resistance (2,438 vs. 1,921 dynes.s.cm-5 in group I, p = 0.05) and end-systolic wall stress (273 vs. 226 kdynes/cm2 in group I, p = 0.06), although mean arterial pressure in the two groups was similar (91 vs. 84 mm Hg in group I, p = 0.22). Group II patients also had higher values for pulmonary vascular resistance (712 vs. 269 dynes.s.cm-5 in group I, p = 0.03) and mean pulmonary artery pressure (47 vs. 29 mm Hg in group I, p = 0.02) despite similar values for mean left atrial pressure (20 vs. 18 mm Hg in group I, p = 0.35). After valvuloplasty, mitral valve area increased by 2.5- and 3-fold, respectively, in group I (to 2.1 cm2) and group II (to 2.0 cm2). Modest increases in left ventricular end-diastolic pressure, end-diastolic stress and end-diastolic volume (+9%) after valvuloplasty were statistically significant only for group II. End-systolic wall stress did not decline in either group II (281 kdynes/cm2) or group I (230 kdynes/cm2), and ejection fraction failed to increase significantly (0.49 to 0.51 for group II and 0.62 to 0.61 for group I) after valvuloplasty. Contractile performance estimated with a preload-corrected ejection fraction-afterload relation was within or near normal limits in all 19 patients in whom it was assessed. CONCLUSIONS: Excessive vasoconstriction may account for the higher afterload, lower ejection performance and lower cardiac output observed in a subset of patients with mitral stenosis because contractile dysfunction could not be detected and left ventricular filling--which was not subnormal despite severe inflow obstruction--improved only modestly after valvuloplasty.

Obstruction of mechanical heart valve prostheses: clinical aspects and surgical management.

One hundred patients (32 male) aged 5 months to 82 years (median 32 years) underwent 106 surgical procedures for 112 mechanical prosthetic valves obstructed by a thrombus (n = 61) or pannus (n = 7), or both (n = 44), between January 1, 1980 and December 31, 1989. The position of the obstructed prosthesis was aortic in 51 patients (48%), mitral in 49 (46%) and both aortic and mitral in 6 (6%). The types of obstructed prosthetic valves were Björk-Shiley (n = 51), St. Jude (n = 41) and Medtronic-Hall (n = 20). The time interval between valve replacement and obstruction ranged from 6 weeks to 13 years (median 4 years). Of 63% of patients in whom coagulation variables were available at the time of obstruction, 70% were receiving inadequate anticoagulant therapy. In 63% of the procedures the patient was in New York Heart Association functional class IV. Two patients underwent preoperative thrombolysis with incomplete results. Operative procedures included valve replacement (n = 81), valve declotting and excision of pannus (n = 23) and aortic valve replacement and mitral valve declotting (n = 2). The early mortality rate was 12.3% (13 patients), and there was no difference between surgery for mitral prostheses (12.2%) versus aortic prostheses (13.7%). The perioperative mortality rate was 17.5% (11 of 63 patients) in patients in functional class IV and 4.7% (2 of 43 patients) in those in functional classes I to III (p less than 0.05). For valve replacement, the mortality rate was 12% (10 of 81 patients) and for declotting of the prosthesis 13% (3 of 23 patients).(ABSTRACT TRUNCATED AT 250 WORDS)

Peripartum cardiomyopathy: analysis of clinical outcome, left ventricular function, plasma levels of cytokines and Fas/APO-1.

OBJECTIVES: 1) To evaluate the outcome of patients with peripartum cardiomyopathy (PPC) on current treatment for heart failure, 2) to assess the circulating plasma levels of cytokines and Fas receptors and 3) to identify predictors of prognosis. BACKGROUND: Previous studies in patients with PPC were done when angiotensin-converting enzyme (ACE) inhibitors and beta-adrenergic blocking agents were not routinely used in heart failure. Inflammatory cytokines play an important role in the pathogenesis and progression of heart failure of other etiologies. However, there is a paucity of data regarding cytokine expression in patients with PPC. Plasma concentrations of Fas receptors (an apoptosis-signalling receptor) have not been reported in this population. METHODS: We followed prospectively 29 consecutive black women with PPC. All patients were treated with diuretics, digoxin, enalapril and carvedilol. Echocardiograms were performed at baseline and after six months of treatment. Cytokine and soluble Fas/APO-1 plasma levels were measured at baseline. RESULTS: Tumor necrosis factor-alpha, interleukin-6 and Fas/APO-1 levels were significantly elevated in the study patients compared with 20 healthy volunteers. Eight patients died. sFas/APO-1 levels were significantly higher in patients who died compared with survivors (8.98 +/- 4.5 vs. 5.33 +/- 3 U/ml, respectively, p = 0.02). At six months, ejection fraction improved from 26.7 +/- 10 to 42.7 +/- 16%, p = 0.00003, with an increment of more than 10 U in 10 patients (28.1 +/- 4 to 51.9 +/- 8%, p = 0.000008). CONCLUSIONS: Cytokine and sFas levels are elevated in patients with PPC. Despite treatment with ACE inhibitors and beta-blockers, mortality remains high. However, in 34% of the patients, left ventricular function almost completely normalized.

A case for early surgery in native left-sided endocarditis complicated by heart failure: results in 203 patients.

From January 1982 to December 1988, 203 consecutive patients were selected for early valve replacement (mean 10 days from time of admission) if they had clinical evidence of native valve endocarditis with 1) vegetations on echocardiography, 2) severe valvular lesions, and 3) heart failure. Surgery was performed within 7 days of admission in 56% of patients and was done urgently because of hemodynamic deterioration in 108 (53%). All vegetations were identified by echocardiography and confirmed macroscopically at surgery. One hundred ten patients had isolated aortic valve infection, 50 had isolated mitral valve infection (p less than 0.05 for aortic vs. mitral) and 43 had double-valve infection. Mean aortic cross-clamp time was 57, 38 and 67 min, respectively. Sixty-four patients (32%) had extensive infection involving the anulus or adjacent tissues, or both; such infection more frequently involved the aortic than the mitral valve (p less than 0.05). Thirty-eight patients (35%) with aortic valve infection had abscess formation compared with 1 patient (2%) with mitral valve infection (p less than 0.05). Only eight patients (4%) died in the hospital. There were seven patients (3%) with a periprosthetic leak and five patients (3%) with early prosthetic valve endocarditis. Long-term follow-up, available in 174 hospital survivors (89%), revealed 10 deaths and two new ring leaks at 38 +/- 22 months. In conclusion, among patients with endocarditis who need surgery for heart failure, aortic valve infection is more prevalent than mitral valve infection and is more often associated with extensive infection, including abscess formation.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of simultaneous alterations in preload and afterload on measurements of left ventricular contractility in patients with dilated cardiomyopathy: comparisons of ejection phase, isovolumetric and end-systolic force-velocity indexes.

OBJECTIVES: The study was designed to critically evaluate the clinical utility of ejection phase and nonejection phase indexes of contractile state in patients with severe left ventricular dysfunction. BACKGROUND: Ejection phase indexes of left ventricular systolic performance are unable to differentiate contractility changes from alterations in loading conditions. Isovolumetric and end-systolic force-velocity indexes have been proposed as alternative measurements of contractile state that are load independent. METHODS: Seventeen patients with nonischemic dilated cardiomyopathy were studied during cardiac catheterization. High fidelity central aortic and left ventricular pressure measurements were made with simultaneous echocardiographic recordings of chamber minor- and long-axis dimensions and wall thickness. Data were acquired under control conditions, during nitroprusside infusion and with dopamine (6 micrograms/kg per min). RESULTS: Patients were classified into those without (group 1, n = 10) and those with (group 2, n = 7) a decrease in end-diastolic circumferential wall stress in response to dopamine. There were no baseline differences between the groups in functional class, left ventricular chamber geometry or cardiovascular hemodynamics. Ejection phase indexes were variably altered by changes in preload, afterload and heart rate, thereby complicating physiologic interpretation of data. Dopamine increased the commonly used isovolumetric index, maximal rate of rise in left ventricular pressure (dP/dtmax), by 64% for group 1 but by only 16% for group 2 (p less than 0.001), resulting in an underestimation of contractile state change in 41% of patients. In contrast, the left ventricular end-systolic circumferential wall stress-rate-corrected velocity of fiber shortening relation, which incorporates afterload, ventricular wall mass and heart rate in its analysis, was a sensitive contractility measurement that was preload independent and equally augmented by dopamine for both groups. CONCLUSIONS: Of the left ventricular contractility indexes evaluated, the end-systolic circumferential wall stress-rate-corrected velocity of fiber shortening relation was the most physiologically appropriate for assessing pharmacologically induced changes in inotropic state that were accompanied by complex alterations in loading conditions in patients with dilated cardiomyopathy.

Long-term (3-month) effects of a new beta-blocker (nebivolol) on cardiac performance in dilated cardiomyopathy.

OBJECTIVES: This study examined the long-term (3-month) effects of nebivolol, a new beta-adrenergic blocking agent, on cardiac performance in patients with dilated cardiomyopathy. BACKGROUND: Several beta-blocking drugs have been reported to have a beneficial hemodynamic effect in patients with dilated cardiomyopathy, but few data obtained in a placebo-controlled randomized study have addressed the mechanisms of improvement. METHODS: Twenty-four patients with dilated idiopathic (n = 22) or ischemic (n = 2) cardiomyopathy (ejection fraction 0.15 to 0.40) in stable New York Heart Association functional class II or III were entered into a double-blind randomized trial of nebivolol, a new, potent, selective beta 1-antagonist. Exercise time, invasive hemodynamic data (12- and 24-h monitoring) and variables of left ventricular function were examined at baseline and after 3 months of orally administered nebivolol (1 to 5 mg/day, n = 11) or placebo (n = 13). RESULTS: Heart rate decreased (group mean 85 to 71 beats/min vs. 87 to 87 beats/min with placebo) and stroke volume increased significantly (group mean 43 to 55 ml vs. 42 to 43 ml) with nebivolol; decreases in systemic resistance, systemic arterial pressure, wedge pressure and pulmonary artery pressure were not significantly different from those with placebo. Similar hemodynamic results were obtained in the catheterization laboratory. Analysis of high fidelity measurements of left ventricular pressure showed a decrease in left ventricular end-diastolic pressure in the nebivolol group (group mean 21 to 15 vs. 24 to 20 mm Hg with placebo) but no change in the maximal rate of pressure development or in two variables of left ventricular relaxation (maximal negative rate of change of left ventricular pressure [dP/dtmax] and the time constant tau). Left ventricular mass decreased (p = 0.04). Despite a decrease in heart rate with nebivolol, there was a slight decrease in left ventricular end-diastolic volume (p = NS). End-systolic volume tended to decrease (p = 0.07) despite no reduction in end-systolic stress. The net result was a significant increase in ejection fraction (group mean 0.23 to 0.33 vs. 0.21 to 0.23 with placebo), presumably as a result of an increase in contractile performance. This effect was corroborated by an increase in a relatively load-independent variable of myocardial performance. CONCLUSIONS: Nebivolol improved stroke volume, ejection fraction and left ventricular end-diastolic pressure, not through a measurable reduction in afterload or a lusitropic effect, but by improving systolic contractile performance.

Efficacy of different drug classes used to initiate antihypertensive treatment in black subjects: results of a randomized trial in Johannesburg, South Africa.

BACKGROUND: Thiazides are recommended to initiate antihypertensive drug treatment in black subjects. OBJECTIVE: To test the efficacy of this recommendation in a South African black cohort. METHODS: Men and women (N = 409), aged 18 to 70 years, with a mean ambulatory daytime diastolic blood pressure between 90 and 114 mm Hg, were randomized to 13 months of open-label treatment starting with the nifedipine gastrointestinal therapeutic system (30 mg/d, n = 233), sustained-release verapamil hydrochloride (240 mg/d, n = 58), hydrochlorothiazide (12.5 mg/d, n = 58), or enalapril maleate (10 mg/d, n = 60). If the target of reducing daytime diastolic blood pressure below 90 mm Hg was not attained, the first-line drugs were titrated up and after 2 months other medications were added to the regimen. RESULTS: While receiving monotherapy (2 months, n = 366), the patients' systolic and diastolic decreases in daytime blood pressure averaged 22/14 mm Hg for nifedipine, 17/11 mm Hg for verapamil, 12/8 mm Hg for hydrochlorothiazide, and 5/3 mm Hg for enalapril. At 2 months the blood pressure of more patients treated with nifedipine was controlled: 133 (63.3%, P

Comparison of single-dose nifedipine and captopril for chronic severe aortic regurgitation.

The effects of a single dose of either nifedipine 20 mg (n = 10) or captopril 50 mg (n = 10) were compared in 20 patients with symptomatic, chronic severe aortic regurgitation using angiography and micromanometer left ventricular pressure measurements. At 90 minutes, mean arterial pressure was reduced comparably after both drugs (86 +/- 15 to 76 +/- 18 mm Hg for nifedipine vs 95 +/- 19 to 77 +/- 18 mm Hg for captopril, p = NS between groups by analysis of variance), as was wedge pressure (11 +/- 5 to 9 +/- 4 mm Hg vs 13 +/- 9 to 9 +/- 5 mm Hg for captopril). Systemic vascular resistance was reduced more (p = 0.01) after nifedipine than after captopril (1,549 +/- 468 to 1,067 +/- 291 dynes s cm-5 vs 1,632 +/- 559 to 1,436 +/- 392 dynes s cm-5). Heart rate declined after captopril (84 +/- 14/min to 75 +/- 15/min, p = 0.002) but not after nifedipine (78 +/- 13 min to 80 +/- 14 min). Forward stroke volume increased after nifedipine (58 +/- 14 to 70 +/- 16 ml, p < 0.001) but not after captopril (58 +/- 17 to 59 +/- 16 ml). Thus, cardiac output increased after nifedipine (4.4 +/- 0.9 to 5.5 +/- 1.2 liters/min, p < 0.001) but decreased after captopril (4.8 +/- 1.2 to 4.3 +/- 1.0, p = 0.004).(ABSTRACT TRUNCATED AT 250 WORDS)

Anterior mitral leaflet retraction--a new echocardiographic predictor of severe mitral regurgitation following balloon valvuloplasty by the Inoue technique.

Echocardiographic quantification of the severity of anterior mitral leaflet retraction aids prediction of severe mitral regurgitation after balloon valvuloplasty.

Effects of a single oral dose of captopril on left ventricular performance in severe mitral regurgitation.

For comparable decreases in systemic resistance, angiotensin-converting enzyme inhibitors produce a lesser increase in cardiac output than do previously used vasodilators. Although the reason for this is not yet clear, the possibility of a negative inotropic effect of angiotensin-converting enzyme inhibitors was demonstrated by intracoronary injection. The effects of an oral dose of captopril on systolic performance were assessed by examining left ventricular (LV) pressure-volume loops obtained with simultaneous cineangiography and micromanometer pressure recordings before and 90 minutes after administration of oral captopril (25 to 50 mg) in 18 patients with chronic, severe mitral regurgitation. Group 1 (n = 9) was given captopril alone, and group 2 (n = 9) was given captopril plus atropine (0.04 mg/kg intravenous) to assess the role of parasympathetic activity in mediating the effects of captopril. Captopril reduced heart rate (90 to 81 beats/min; p less than 0.002) and LV end-diastolic pressure (13 to 10 mm Hg; p = 0.03), despite a slight increase in end-diastolic volume (257 to 264 ml; p = not significant) that suggests improved diastolic properties. Despite a decrease in end-systolic pressure (103 to 90 mm Hg; p less than 0.001), ejection fraction did not increase (0.60 to 0.58; p = not significant) owing to an increase in end-systolic volume (107 to 114 ml; p = 0.008). Contractile performance, estimated from the end-systolic pressure/volume quotient, was consistently depressed by captopril, as was the relation of preload-corrected ejection fraction to end-systolic stress.(ABSTRACT TRUNCATED AT 250 WORDS)

Effectiveness of enalapril in combination with low-dose hydrochlorothiazide versus enalapril alone for mild to moderate systemic hypertension in black patients.

The importance of concomitant low-dose hydrochlorothiazide was assessed in black hypertensive patients treated with enalapril. Left ventricular (LV) mass and function, metabolic parameters, 24-hour ambulatory blood pressure (BP), exercise duration, and systolic BP response were evaluated before and after drug therapy. Enalapril 20 mg (group 1) or enalapril 20 mg plus hydrochlorothiazide 12.5 mg (single tablet; group 2) was given to 38 patients for 9 weeks in a double-blind, placebo-controlled, randomized study. LV mass measured 61 +/- 17 versus 102 +/- 23 g/m2, and 24-hour ambulatory BP measured 120 +/- 8/75 +/- 6 versus 155 +/- 12/100 +/- 6 mm Hg in matched control subjects (n = 40) versus hypertensive patients, respectively. No clinically important changes occurred in total cholesterol, serum uric acid or potassium in either group. Enalapril slightly reduced 24-hour ambulatory BP from 154 +/- 15/100 +/- 7 mm Hg to 148 +/- 19/96 +/- 11 mm Hg after treatment (p < 0.05 for systolic BP); systolic BP load (70% to 59%, p < 0.05), and diastolic BP load (67% to 60%, p = NS) decreased. Baseline BP decreased from 157 +/- 9/101 +/- 6 to 132 +/- 13/86 +/- 8 mm Hg (p < 0.0001); systolic BP load (64% to 29%, p < 0.0001), and diastolic BP load (64% to 33%, p < 0.0001) decreased in group 2. Exercise systolic BP was attenuated (p = 0.007, group 2; p = NS, group 1) and duration increased (p = NS) only in group 2.(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of mitral regurgitation and volume loading on pressure half-time before and after balloon valvotomy in mitral stenosis.

Doppler pressure half-time (PHT) is frequently used to assess mitral valve area (MVA), but the reliability of PHT has recently been challenged, specifically in the setting of balloon mitral valvotomy when hemodynamics have been abruptly altered. The effect of volume loading both before and after balloon mitral valvotomy on computation of MVA by Gorlin and by PHT in 18 patients with high-fidelity micromanometer measurements of left atrial and left ventricular pressure was therefore examined. Echocardiographic MVA increased from 0.91 +/- 0.15 to 1.97 +/- 0.42 cm2 after valvotomy. Volume loading produced significant increases in left atrial pressure (16 to 23 before and 12 to 20 mm Hg after valvotomy), in cardiac output (3.7 to 4.1 before and 3.9 to 4.6 liters/min after valvotomy), and in mitral valve gradient (11 to 14 before and 5 to 7 mm Hg after valvotomy). These hemodynamic changes were associated with modest but significant decreases in PHT and increases in MVA estimated by 220/PHT (0.66 to 0.81 before and 1.64 to 1.96 cm2 after valvotomy), whereas the MVA by Gorlin was not affected in a consistent fashion by volume loading (0.85 to 0.89 before and 1.66 to 1.69 cm2 after valvotomy). The correlation between Gorlin MVA and 220/PHT was only fair (r = 0.73, p less than 0.001) and was significantly poorer among patients with greater than 1+ mitral regurgitation (r = 0.72) than among those with less or no regurgitation (r = 0.79) (p = 0.001 by analysis of covariance for mitral regurgitation effect).(ABSTRACT TRUNCATED AT 250 WORDS)

Long-term follow-up of St. Jude Medical prosthesis in a young rheumatic population using low-level warfarin anticoagulation: an analysis of the temporal distribution of causes of death.

This study assesses the long-term (mean 52+/-24 months) performance of the St. Jude Medical (SJM) valve in 200 young (mean age 31+/-13 years) rheumatic patients on low-level warfarin anticoagulation combined with dipyridamole. Follow-up was 95% complete and comprised 867 patient-years. There were 33 deaths (3.8%/patient-year). Death was valve related in 12 cases and due to left ventricular dysfunction in 10. Death due to left ventricular dysfunction occurred earlier after surgery than death due to other causes (10+/-7 vs 29+/-18 months, p <0.005); these patients had larger preoperative left ventricular dimensions than the rest of the group (end-systolic diameter 51+/-13 vs 37+/-16 mm, end-diastolic diameter 66+/-13 vs 50+/-19 mm, p = 0.006). Actuarial probability of survival was 81% at 86 months and probability of event-free survival was 71%. The median international normalized ratio was 1.88+/-0.54. Thromboembolism (13 events) occurred at a linearized rate of 1.5%/patient-year. There were 11 major bleeding episodes (1.3%/patient-year), 4 cases of prosthetic valve endocarditis (0.8%/patient-year), and 12 paraprosthetic leaks (1.4%/patient-year). No valve obstructions or reoperations occurred. Thus, the SJM valve performs well on low-level anticoagulation combined with dipyridamole. Left ventricular dysfunction was a common cause of death in the early postoperative period.

Comparison of intravenous amrinone and dobutamine in congestive heart failure due to idiopathic dilated cardiomyopathy.

A prospective randomized study was performed in 46 consecutive patients with refractory congestive heart failure (CHF) due to idiopathic dilated cardiomyopathy to compare the hemodynamic responses to 48-hour infusions of amrinone and dobutamine. Both drugs substantially reduced pulmonary arterial wedge pressure, right atrial pressure and systemic vascular resistance and increased cardiac index. Amrinone caused a greater decrease in right atrial pressure than dobutamine (p less than 0.02) and had a positive chronotropic effect not observed with dobutamine (p less than 0.01). The increase in heart rate produced by amrinone correlated inversely with the changes in right atrial and pulmonary arterial wedge pressures, suggesting a baroreceptor response to reduced preload. Dobutamine produced a larger increase in stroke volume index than amrinone (p less than 0.01). Ninety-one percent of patients receiving amrinone and only 65% receiving dobutamine had reduction of greater than or equal to 30% in pulmonary arterial wedge pressure (p less than 0.05). Cardiac index increased greater than or equal to 30% in similar numbers of patients given amrinone (74%) and dobutamine (65%). Negative fluid balance was recorded in all patients receiving amrinone and in 78% of patients receiving dobutamine (p less than 0.05). Target hemodynamic criteria were achieved in 83% of patients receiving 10 micrograms/kg/min of amrinone. The effective maintenance dose of dobutamine was extremely variable. No clinically important adverse effects were observed with either drug regimen. Both amrinone and dobutamine are effective and safe agents for short-term parenteral therapy of patients with dilated cardiomyopathy in severe CHF that is unresponsive to oral medication.(ABSTRACT TRUNCATED AT 250 WORDS)

Frequency and severity of intravascular hemolysis after left-sided cardiac valve replacement with Medtronic Hall and St. Jude Medical prostheses, and influence of prosthetic type, position, size and number.

Intravascular hemolysis occurs often in patients with mechanical heart valve prostheses, but in most cases is of mild degree and subclinical. The severity of hemolysis is reported to be related to the type, position and size of prostheses used, as well as the presence of valve malfunction. Hemolysis was evaluated in 170 patients with St. Jude Medical (SJM) and 80 patients with Medtronic Hall (MH) prostheses, with normal mechanical function. The presence and severity of hemolysis was assessed on the basis of serum lactic dehydrogenase, serum haptoglobin, blood hemoglobin and reticulocyte levels as well as the presence of schistocytes. Overall, patients with SJM prostheses had greater frequency (51.2 vs 18.7%, p < 0.005) and severity (p < 0.005) of hemolysis than patients with MH prostheses, irrespective of position and size. No patient had decompensated anemia. The frequency of hemolysis was similar in both groups with double-valve replacement, whereas severity was greater with SJM than MH prostheses (p < 0.001). The number and position of the prostheses were correlated with severity of hemolysis: Double-valve replacement and mitral position were correlated with greater hemolysis than single-valve replacement (p < 0.01) and aortic position (p < 0.01). Valve size, cardiac rhythm and time from operation did not correlate either with frequency or severity of hemolysis. It is concluded that in normally functioning SJM and MH prostheses: (1) hemolysis is frequent but never severe; (2) SJM demonstrates greater frequency and severity when compared with MH valve; and (3) number, position, but not size, significantly affect the severity of hemolysis.

Beneficial effect of atrial pacing in severe acute aortic regurgitation and role of M-mode echocardiography in determining the optimal pacing interval.

The effect of atrial pacing on cardiac performance was assessed in 11 men (aged 20 to 64 years) with recent-onset severe aortic regurgitation (AR), all of whom had diastolic closure of the mitral valve on the echocardiogram. Thermodilution cardiac outputs were determined, and aortic, left ventricular and pulmonary arterial wedge pressures recorded. Once baseline recordings were completed, the pacing rate was increased by increments of 10 beats/min (70, 80, 90...) to a maximal rate of 140 beats/min. The optimal pacing interval, obtained from hemodynamic data, was defined as that at which the lowest filling pressure was associated with the highest cardiac index. This was then compared with a pacing interval derived from the R wave of the electrocardiogram to the diastolic mitral closing point on the M-mode echocardiogram. Such an interval would shorten diastole without affecting forward mitral flow. Atrial pacing improved the overall hemodynamic state in all patients; the most favorable hemodynamics were achieved at heart rates between 110 and 130 beats/min (mean: 120 +/- 8). At the optimal rate, left ventricular end-diastolic pressure decreased from 46 +/- 7 to 23 +/- 12 mm Hg (p less than 0.001), and the pulmonary arterial wedge pressure from 28 +/- 8 to 16 +/- 7 mm Hg (p less than 0.001), while the cardiac index increased from 2.34 +/- 0.46 to 2.63 +/- 0.49 liters/min/m2 (p less than 0.01). The mean difference between the optimal pacing interval determined from the hemodynamic data and the interval derived from the echocardiogram was 18 +/- 21 ms.(ABSTRACT TRUNCATED AT 250 WORDS)

Results of percutaneous balloon mitral valvotomy in young adults.

The results of percutaneous balloon mitral valvotomy (PBMV) were evaluated in 235 young patients (mean age 29 +/- 11 years) with symptomatic rheumatic mitral stenosis, and the single-balloon Inoue technique was compared with the double-balloon Mansfield technique. PBMV was associated with a significant increase in Gorlin mitral valve area (0.78 +/- 0.23 to 1.61 +/- 0.64 cm2; p < 0.001), and improvement in New York Heart Association functional class (2.78 +/- 0.59 to 1.28 +/- 0.58; p < 0.001). Mitral regurgitation increased significantly (0.4 +/- 0.6 to 1.3 +/- 1.0; p < 0.001), but was significant (> or = 3+) only in 19 patients (8%). Comparison of the Inoue and Mansfield techniques showed a significantly lower Gorlin mitral valve area after PBMV (1.55 +/- 0.56 vs 1.74 +/- 0.74 cm2; p < 0.05), but a lower incidence of mitral regurgitation by color Doppler echocardiography (1.1 +/- 0.7 vs 1.5 +/- 0.8; p < 0.05) in the Inoue group. Patients were divided into those with nonpliable (valve score > 8; group I) and pliable (score < or = 8; group II) valves. Although significant increases in mitral valve area were obtained in both groups, mitral valve area by planimetry was significantly lower in group I (1.49 +/- 0.46 vs 1.86 +/- 0.44 cm2; p < 0.05), whereas there was no difference in the amount of color Doppler mitral regurgitation (1.5 +/- 1.0 vs 1.2 +/- 0.7; p = NS).(ABSTRACT TRUNCATED AT 250 WORDS)