Isradipine improves endothelium-dependent vasodilation in normotensive coronary artery disease patients with hypercholesterolemia.

OBJECTIVE: The dihydropyridine calcium antagonist isradipine has anti-atherosclerotic effects in animals and improves endothelium-mediated nitric oxide (NO)-dependent vasodilation in vitro. As improved endothelial function may be beneficial we investigated its effects in patients with a high likelihood of endothelial dysfunction. DESIGN: Thirty patients (two female, age 55.4 +/- 10.5 years) with known coronary artery disease and elevated (> 6 mmol/l) total cholesterol (cholesterol: mean 6.7 +/- 0.78 mmol/l) or a cholesterol/high density lipoproteins (HDL) ratio of > 5 not on lipid lowering therapy, participated in the study. Endothelial vasodilator function was assessed before and after double-blind, randomized administration of isradipine 5 mg/day or placebo for 3 months. METHODS: Endothelial function was assessed as forearm blood flow (FBF, venous occlusion plethysmography) responses to graded brachial artery infusions of acetylcholine (Ach), to the NO-synthase blocker NG-monomethyl-L-arginine (L-NMMA) and to the endothelium-independent vasodilator sodium nitroprusside (SNP). Blood pressure was measured either directly from the brachial arterial or by sphygmomanometer during clinic visits. RESULTS: Blood pressure was unchanged in both groups after 3 months (isradipine: 88.8 versus 92.1 mmHg; placebo: 81.0 versus 82.5 mmHg; NS) but cholesterol levels decreased similarly in both groups (isradipine: 6.7 versus 6.1 mmol/l, NS; placebo: 6.6 versus 5.9 mmol/l, P< 0.05). The vasodilator response to SNP and the decrease in FBF in response to blockade of NO synthesis by L-NMMA were unchanged in both groups. However, isradipine, but not placebo, enhanced the NO-dependent vasodilator response to Ach (P < 0.05). CONCLUSION: Isradipine improves acetylcholine-mediated vasodilation in hypercholesterolemic patients independent of changes in lipids or blood pressure.

Rationale and perspective of endothelin-1 antagonism in acute heart failure.

A role of the potent and long-acting vasoconstrictor peptide endothelin (ET)- I in the pathophysiology of chronic human heart failure has been postulated, based upon indirect evidence such as elevated plasma ET-1 levels and their relationship to the degree of haemodynamic impairment. Acute heart failure shares many features of chronic heart failure, albeit in an exaggerated fashion. As both the mixed ETA/ETB-receptor antagonist bosentan and the selective ETA receptor antagonist BQ 123 acutely improved the haemodynamics of chronic heart failure patients, there seems to be good reason to believe that ET-1 receptor antagonism may also be of benefit in the setting of acute heart failure. However, appropriate trials will have to be performed to document the clinical benefit of such an approach. Finally, the question remains open as to whether mixed ET-1 receptor antagonists like bosentan will prove better, worse or equal to antagonists that block the ETA, receptor only.

[Long-term results of the surgical treatment in acute aortic valve endocarditis]. / Langzeitresultate der chirurgischen Behandlung der akuten Aortenklappenendokarditis.

Late results after surgery for acute infectious aortic endocarditis using allografts are compared with those achieved with bioprostheses or mechanical heart valves. Cryopreserved allografts were used in 74 (22%) and prosthetic heart valve in 262 out of 336 (78%) patients presenting acute aortic endocarditis. Prosthetic (p = 0.001) and destructive endocarditis (p = 0.001) were more frequent in patients receiving allografts. Mean follow-up time was 6.6 +/- 4 years (range, 3 to 28 years). The 30-day-mortality was 19% for allograft patients and 6% for those receiving prosthetic heart valves (p = 0.002). Early reoperation, postoperative renal failure and sepsis did not differ between groups. After 20 years, actuarial survival was 60% for mechanical heart valves, 44% for bioprosthesis and 38% for allografts (p = 0.003), reoperation was unnecessary in 52% of mechanical heart valves and 10% of bioprostheses and allografts (p = 0.0007). Acute infection at the time of operation (p = 0.0001), redo surgery (p = 0.0006), staphylococci (p = 0.0003), older age (p = 0.004) and mitral valve involvement (p = 0.004) were risk factors for late death, irrespective of preoperative antibiotic treatment and type of prosthesis used. A longer bypass and aortic cross-clamp time predicted early (p = 0.0001) and late survival (p = 0.0001), independently. Destructive aortic endocarditis has a poor long-term outcome irrespective of the use of allografts. Acute infection at the time of surgery predicted early and late death; however, surgery is indicated prior to secondary involvement of the mitral valve. The duration of preoperative antibiotic treatment did not affect outcome. A thorough surgical technique directly influences early and late survival.

[Timing of reoperation of degenerated aortic and mitral bioprostheses]. / Zeitpunkt der Reoperation bei degenerierten aortalen und mitralen Bioprothesen.

Reoperative surgery for degenerated aortic and mitral valve bioprostheses has a considerable mortality. This study compares life expectancy, mode of failure and predictors for emergency reoperation and reoperative mortality between degenerated aortic and mitral bioprostheses. A total of 265 bioprosthetic valve patients, 172 aortic and 93 mitral patients, were followed to assess the time period between first and redo valve replacement. Mean life expectancy for aortic bioprostheses was 10.4 +/- 4.3 (2 to 28.6) years, whereas it was 10.0 +/- 3.7 (0.9 to 20) years for mitral bioprostheses (group M). Emergency reoperation had to be performed in 31/172 group A (18%) and 16/93 group M (17%) patients. In group A, the reoperative mortality was 5.2%; it was 1.4% for elective and 22.6% for emergency reoperation (p < 0.0001; OR = 20.3). Reoperative mortality in group M patients was 5.4% and did not differ between elective and emergency surgery. Group A patients who died at reoperation had higher transvalvular gradients before the first operation (p = 0.007), received smaller sized bioprostheses (p = 0.03) and had a higher incidence of coronary artery disease (p = 0.001) and pulmonary artery hypertension (p = 0.009) acquired during the interval. Endocarditis being the reason for primary surgery (p = 0.004), postoperative pneumonia after the first procedure (p = 0.005), pulmonary artery hypertension (p = 0.0004), later recurrence of symptoms of valve degeneration (p = 0.04), acute onset of bioprosthetic regurgitation (p = 0.00002) and a lower left ventricular ejection fraction (p = 0.03) were risk factor for emergency surgery. There were no predictors of reoperative mortality identified in mitral valve patients. The life expectancy of aortic and mitral bioprostheses is acceptable even in a relatively young patient population (mean age 46 +/- 13 in group A and 45 +/- 12 years in group M patients). Patients with degenerated aortic bioprostheses undergoing emergency reoperation have an extraordinary high reoperative mortality. They can be identified as patients who had a history of endocarditis and higher transvalvular gradients prior to the first operation, who received smaller sized bioprostheses and acquired coronary artery disease and pulmonary artery hypertension during the interval. Thus, emergency reoperation is preventable, increasing overall life expectancy of patients with bioprostheses. There were no risk factors for reoperative mortality identified in bioprosthetic mitral valve patients.

[Long-term results after surgery for acute aortic endocarditis]. / Langzeitresultate der chirurgischen Behandlung der akuten Aortenklappenendokarditis.

Late results after surgery for acute infectious aortic endocarditis using allografts are compared with those achieved with bioprostheses or mechanical heart valves. Cryopreserved allografts were used in 74 (22 %) and prosthetic heart valve in 262 out of 336 (78 %) patients presenting acute aortic endocarditis. Prosthetic (p = 0.001) and destructive endocarditis (p = 0.001) were more frequent in patients receiving allografts. Mean follow-up time was 6.6 ± 4 years (range, 3 to 28 years). The 30-daymortality was 19 % for allograft patients and 6 % for those receiving prosthetic heart valves (p = 0.002). Early reoperation, postoperative renal failure and sepsis did not differ between groups. After 20 years, actuarial survival was 60 % for mechanical heart valves, 44 % for bioprosthesis and 38 % for allografts (p = 0.003), reoperation was unnecessary in 52 % of mechanical heart valves and 10 % of bioprostheses and allografts (p = 0.0007). Acute infection at the time of operation (p = 0.0001), redo surgery (p = 0.0006), staphylococci (p = 0.0003), older age (p = 0.004) and mitral valve involvement (p = 0.004) were risk factors for late death, irrespective of preoperative antibiotic treatment and type of prosthesis used. A longer bypass and aortic cross-clamp time predicted early (p = 0.0001) and late survival (p = 0.0001), independently. Destructive aortic endocarditis has a poor long-term outcome irrespective of the use of allografts. Acute infection at the time of surgery predicted early and late death; however, surgery is indicated prior to secondary involvement of the mitral valve. The duration of preoperative antibiotic treatment did not affect outcome. A thorough surgical technique directly influences early and late survival.

[Timing of reoperation of degenerated aortic and mitral bioprostheses]. / Zeitpunkt der Reoperation bei degenerierten aortalen und mitralen Bioprothesen.

Reoperative surgery for degenerated aortic and mitral valve bioprostheses has a considerable mortality. This study compares life expectancy, mode of failure and predictors for emergency reoperation and reoperative mortality between degenerated aortic and mitral bioprostheses. A total of 265 bioprosthetic valve patients, 172 aortic and 93 mitral patients, were followed to assess the time period between first and redo valve replacement. Mean life expectancy for aortic bioprostheses was 10.4 ± 4.3 (2 to 28.6) years, whereas it was 10.0 ± 3.7 (0.9 to 20) years for mitral bioprostheses (group M). Emergency reoperation had to be performed in 31/172 group A (18 %) and 16/93 group M (17 %) patients. In group A, the reoperative mortality was 5.2 %; it was 1.4 % for elective and 22.6 % for emergency reoperation (p < 0.0001; OR = 20.3). Reoperative mortality in group M patients was 5.4 % and did not differ between elective and emergency surgery. Group A patients who died at reoperation had higher transvalvular gradients before the first operation (p = 0.007), received smaller sized bioprostheses (p = 0.03) and had a higher incidence of coronary artery disease (p = 0.001) and pulmonary artery hypertension (p = 0.009) acquired during the interval. Endocarditis being the reason for primary surgery (p = 0.004), postoperative pneumonia after the first procedure (p = 0.005), pulmonary artery hypertension (p = 0.0004), later recurrence of symptoms of valve degeneration (p = 0.04), acute onset of bioprosthetic regurgitation (p = 0.00002) and a lower left ventricular ejection fraction (p = 0.03) were risk factor for emergency surgery. There were no predictors of reoperative mortality identified in mitral valve patients. The life expectancy of aortic and mitral bioprostheses is acceptable even in a relatively young patient population (mean age 46 ± 13 in group A and 45 ± 12 years in group M patients). Patients with degenerated aortic bioprostheses undergoing emergency reoperation have an extraordinary high reoperative mortality. They can be identified as patients who had a history of endocarditis and higher transvalvular gradients prior to the first operation, who received smaller sized bioprostheses and acquired coronary artery disease and pulmonary artery hypertension during the interval. Thus, emergency reoperation is preventable, increasing overall life expectancy of patients with bioprostheses. There were no risk factors for reoperative mortality identified in bioprosthetic mitral valve patients.

Preoperative predictors of recurrent atrial fibrillation late after successful mitral valve reconstruction.

OBJECTIVE: Late outcome after mitral valve repair was examined to define preoperative predictors of recurrent atrial fibrillation late after successful mitral valve reconstruction. METHODS: One hundred and eighty-nine patients, 112 with preoperative sinus rhythm and 72 with preoperative chronic or intermittent atrial fibrillation, were followed for 12.2 +/- 10 years after valve repair. Clinic, hemodynamic end echocardiographic data were entered into Cox-regression and Kaplan-Meyer analysis to assess predictors for recurrent atrial fibrillation late after successful mitral valve repair. RESULTS: Univariate and multivariate predictors for recurrent atrial fibrillation late after successful mitral valve reconstruction were preoperative atrial fibrillation (P = 0.0001), preoperative antiarrhythmic drug treatment (P = 0.005), heart rate (P = 0.01), left ventricular ejection fraction (P = 0.01) and increased left ventricular posterior wall thickness (P = 0.05). Patients > 57.5 years with a mean pulmonary artery pressure > or =23 mm Hg and a history of preoperative antiarrhythmic drug treatment had an odds ratio of 53.33 (95% confidence limits 6.12-464.54) for atrial fibrillation late after successful mitral valve repair. CONCLUSION: Older patients with a history of atrial fibrillation, antiarrhythmic treatment or an elevated pulmonary artery pressure may present atrial fibrillation late after successful mitral valve repair. They could be considered for combined mitral valve reconstruction and surgery for atrial fibrillation even though sinus rhythm is present preoperatively.

Prognosis of medically treated patients referred for cardiac transplantation.

OBJECTIVES: To assess prognosis and factors influencing survival of transplant candidates in whom continued medial therapy was recommended in comparison to that of immediately listed patients. METHODS: Retrospective analysis of clinical, echocardiographic and hemodynamic data as related to survival or listing for transplantation of medically treated transplant candidates. PATIENTS: 160 patients considered 'too well' for cardiac transplantation and 133 patients immediately listed for transplantation. RESULTS: Forty-one of the medically treated patients deteriorated clinically and were listed after 10.7+/-12.3 months after initial evaluation. Mid-term prognosis (2 years) of patients never listed was comparable to that of immediately listed patients (74% vs. 70%) but long-term prognosis (5 years) was worse (41% vs. 54%, p<0.001). Cardiothoracic ratio and pulmonary capillary wedge pressure were independent predictors of survival (multivariate analysis) in patients whose NYHA class and physical working capacity improved and cardiothoracic ratio decreased significantly after adjustment of medical therapy. CONCLUSIONS: Mid-term prognosis of selected patients considered 'too well' for transplantation is comparable to patients immediately listed. Lower left ventricular filling pressures, smaller hearts on chest X-ray on initial evaluation, and improvement of symptoms during follow up may identify a subgroup of patients who do well on optimized therapy.

[Pharmacologic therapy of severe heart failure]. / Die medikamentöse Therapie der schweren Herzinsuffizienz.

Improvement of symptoms and, accordingly, quality of life, as well as prolongation of life, are the objectives of drug therapy in congestive heart failure patients. Diuretics are most effective in relieving symptoms related to congestion, and angiotensin converting enzyme inhibitors improve exercise capacity, reduce the incidence of decompensations and hence hospitalizations, and prolong life. Angiotensin type-1 receptor antagonists also seem to improve survival, while digoxin improves symptoms and morbidity but not survival in patients in sinus rhythm. The value of prophylactic antiarrhythmic therapy with amiodarone and oral anticoagulation in the presence of sinus rhythm is not established, and the role of newer dihydropyridine calcium antagonists and betablockers is also not precisely defined. These agents should only be considered in selected cases after careful consideration of potential advantages and risks, and should usually be used as an addition to established therapy. Better understanding of the pathophysiology of congestive heart failure will lead to the development of new treatment concepts, the clinical relevance of which will have to be tested in appropriately designed clinical trials.