Use of an intrapericardial, continuous-flow, centrifugal pump in patients awaiting heart transplantation.

BACKGROUND: Contemporary ventricular assist device therapy results in a high rate of successful heart transplantation but is associated with bleeding, infections, and other complications. Further reductions in pump size, centrifugal design, and intrapericardial positioning may reduce complications and improve outcomes. METHODS AND RESULTS: We studied a small, intrapericardially positioned, continuous-flow centrifugal pump in patients requiring an implanted ventricular assist device as a bridge to heart transplantation. The course of investigational pump recipients was compared with that of patients implanted contemporaneously with commercially available devices. The primary outcome, success, was defined as survival on the originally implanted device, transplantation, or explantation for ventricular recovery at 180 days and was evaluated for both noninferiority and superiority. Secondary outcomes included a comparison of survival between groups and functional and quality-of-life outcomes and adverse events in the investigational device group. A total of 140 patients received the investigational pump, and 499 patients received a commercially available pump implanted contemporaneously. Success occurred in 90.7% of investigational pump patients and 90.1% of controls, establishing the noninferiority of the investigational pump (P<0.001; 15% noninferiority margin). At 6 months, median 6-minute walk distance improved by 128.5 m, and both disease-specific and global quality-of-life scores improved significantly. CONCLUSIONS: A small, intrapericardially positioned, continuous-flow, centrifugal pump was noninferior to contemporaneously implanted, commercially available ventricular assist devices. Functional capacity and quality of life improved markedly, and the adverse event profile was favorable. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00751972.

Vigabatrin-induced peripheral visual field defects in patients with refractory partial epilepsy.

PURPOSE: Vigabatrin can cause retinopathy, resulting in bilateral visual field constriction. Previous analyses of results from a prospective, observational study assessing vigabatrin-induced visual field constriction (described below) employed a partially subjective interpretation of static perimetery. To affirm these previous findings through more objective, quantitative methodology, we now report data from a subset analysis of refractory partial epilepsy patients in the study who underwent Goldmann kinetic perimetry. METHODS: Patients aged ≥ 8 years with refractory partial seizures were enrolled and grouped: those receiving vigabatrin for ≥ 6 months (Group I); those who had received vigabatrin for ≥ 6 months and then had discontinued for ≥ 6 months (Group II); and those naïve to vigabatrin (Group III). Patients underwent static or kinetic perimetry, or both, every 4-6 months for ≤ 3 years. For kinetic perimetry, the temporal and nasal visual fields were measured along the horizontal meridian with the largest (V4e, IV4e) and smallest (I2e, I1e) isopters, respectively. RESULTS: Of 735 patients enrolled, 341 had Goldmann perimetry data. Of these, 258 received vigabatrin. Sixteen percent of vigabatrin-exposed patients had moderate visual field defects (30-60° retained temporal vision), and 3% had severe defects (< 30° retained temporal vision). Visual function questionnaire results indicated a weak correlation between visual field constriction severity and visual symptoms. CONCLUSIONS: These results affirm both an analysis of the same study based primarily on static perimetry and findings from cross-sectional studies. The present analysis verifies that visual field constriction, when it occurs, is most often mild or moderate and is not associated with symptoms of abnormal visual function. The clinical decision to prescribe vigabatrin should be based on a benefit-risk analysis for each individual patient.

Vigabatrin for the treatment of infantile spasms: final report of a randomized trial.

A large randomized study was conducted in patients with newly diagnosed infantile spasms to compare 2 doses of vigabatrin in achieving spasm cessation. High (100-148 mg/kg/d) and low (18-36 mg/kg/d) oral doses of vigabatrin were evaluated in a randomized, single-blind study of 14 to 21 days with subsequent open-label treatment up to 3 years. Spasm cessation was defined as 7 consecutive days of spasm freedom beginning within the first 14 days, confirmed by video-electroencephalogram. A total of 221 subjects comprised the modified intent-to-treat cohort. More subjects in the high-dose group achieved spasm cessation compared with the low-dose vigabatrin group (15.9% [17/107] vs 7.0% [8/114]; P = .0375). During follow-up, 39 of 171 (23%) subjects relapsed; 28 of 39 (72%) regained spasm freedom. Adverse events were primarily mild to moderate in severity. Vigabatrin had a dose-dependent effect in spasm reduction. Spasm cessation occurred rapidly and was maintained in the majority of infants.

Efficacy and safety of the selective aldosterone blocker eplerenone in Japanese patients with hypertension: a randomized, double-blind, placebo-controlled, dose-ranging study.

Approximately 40% of Japanese patients with essential hypertension, including low-renin hypertension, are inadequately managed. Low-renin hypertension generally responds poorly to angiotensin-converting enzyme inhibitors and angiotensin-receptor blockers, but may respond more optimally to diuretics, calcium channel blockers, and aldosterone blockers. This multicenter, randomized, double-blind, placebo-controlled, parallel-group, dose-ranging study evaluated the efficacy and safety of the selective aldosterone blocker eplerenone in 193 Japanese patients with essential hypertension. Although not a study inclusion criterion, baseline active plasma renin levels were consistently low (5.7-10.1 mU/L); most patients met the criteria for low-renin hypertension (< or =42.5 mU/L; normal range, 7-76 mU/L). Patients received placebo or eplerenone 50, 100, or 200 mg once daily for 8 weeks. Systolic blood pressure decreased significantly (-6.8 to -10.6 mm Hg vs. -2.1 mm Hg; p< or =0.0022 vs. placebo). Eplerenone offers significant blood pressure reduction with good tolerability in Japanese patients with hypertension, including those with low-renin hypertension.

Symptoms and the distress they cause: comparison of an aldosterone antagonist and a calcium channel blocking agent in patients with systolic hypertension.

BACKGROUND: Although there has been increasing recognition that a substantial part of the cardiovascular, central nervous system, and renal conditions induced by renin-angiotensin-aldosterone system activation reflects an action of aldosterone, the potential influence of therapy designed to block aldosterone has been limited by the fact that spironolactone (until recently the only aldosterone antagonist available) exerts a substantial array of adverse effects. We sought to compare the magnitude of the distress induced by a widely used calcium channel blocking agent, amlodipine, and a new aldosterone antagonist, eplerenone, in patients treated for systolic hypertension. METHODS: A total of 269 patients older than 50 years with systolic hypertension were randomized to either eplerenone, 50 mg/d, or amlodipine, 2.5 mg/d, and titrated to a maximum 200-mg eplerenone dose or 10-mg amlodipine dose. Patients were followed up for 24 weeks. Quality-of-life questionnaires (SF-36 Health Survey) and a validated instrument for assessing symptom distress (Symptom Distress Index) were administered at randomization and 24 weeks after starting treatment. RESULTS: The systolic blood pressure response to eplerenone and amlodipine did not differ (eplerenone = -20.5 mm Hg and amlodipine = -20.1 mm Hg). For the quality-of-life analysis, 119 patients were randomized to eplerenone and 122 to amlodipine. No significant treatment group differences in the Symptom Distress Index were detected at baseline. There was an overall significant treatment effect on symptom distress in favor of eplerenone (P =.03). Indeed, Symptom Distress Index showed significant worsening distress in 36 of 71 symptoms in the amlodipine arm and none in the eplerenone arm. Significant treatment effect in favor of eplerenone was observed in 5 symptoms: ankle swelling, weight gain, nocturia, increased urination, and shortness of breath. Patients with symptom distress also showed an erosion of psychosocial measures of quality of life (P<.001). CONCLUSIONS: The aldosterone antagonist eplerenone is substantially better tolerated than the widely used calcium-channel blocking agent amlodipine, with comparable reductions in systolic blood pressure. This feature should improve therapeutics in patients in whom blockade of aldosterone's effect would be helpful.

Eplerenone, a selective aldosterone blocker, in patients with left ventricular dysfunction after myocardial infarction.

BACKGROUND: Aldosterone blockade reduces mortality and morbidity among patients with severe heart failure. We conducted a double-blind, placebo-controlled study evaluating the effect of eplerenone, a selective aldosterone blocker, on morbidity and mortality among patients with acute myocardial infarction complicated by left ventricular dysfunction and heart failure. METHODS: Patients were randomly assigned to eplerenone (25 mg per day initially, titrated to a maximum of 50 mg per day; 3319 patients) or placebo (3313 patients) [correction] in addition to optimal medical therapy. The study continued until 1012 deaths occurred. The primary end points were death from any cause and death from cardiovascular causes or hospitalization for heart failure, acute myocardial infarction, stroke, or ventricular arrhythmia. RESULTS: During a mean follow-up of 16 months, there were 478 deaths in the eplerenone group and 554 deaths in the placebo group (relative risk, 0.85; 95 percent confidence interval, 0.75 to 0.96; P=0.008). Of these deaths, 407 in the eplerenone group and 483 in the placebo group were attributed to cardiovascular causes (relative risk, 0.83; 95 percent confidence interval, 0.72 to 0.94; P=0.005). The rate of the other primary end point, death from cardiovascular causes or hospitalization for cardiovascular events, was reduced by eplerenone (relative risk, 0.87; 95 percent confidence interval, 0.79 to 0.95; P=0.002), as was the secondary end point of death from any cause or any hospitalization (relative risk, 0.92; 95 percent confidence interval, 0.86 to 0.98; P=0.02). There was also a reduction in the rate of sudden death from cardiac causes (relative risk, 0.79; 95 percent confidence interval, 0.64 to 0.97; P=0.03). The rate of serious hyperkalemia was 5.5 percent in the eplerenone group and 3.9 percent in the placebo group (P=0.002), whereas the rate of hypokalemia was 8.4 percent in the eplerenone group and 13.1 percent in the placebo group (P<0.001). CONCLUSIONS: The addition of eplerenone to optimal medical therapy reduces morbidity and mortality among patients with acute myocardial infarction complicated by left ventricular dysfunction and heart failure.