The American journal of cardiology
-
Interventions involving calcium cycling may represent a promising approach to heart failure (HF) therapy because calcium handling is known to be deranged in human and experimental HF. Istaroxime is a sodium-potassium adenosine triphosphatase (ATPase) inhibitor with the unique property of increasing sarcoplasmic reticulum calcium ATPase (SERCA) isoform 2a (SERCA2a) activity. Because this was demonstrated in normal experimental models, we investigated whether istaroxime is able to improve global cardiac function and stimulate SERCA in failing hearts. ⋯ In left ventricular sarcoplasmic reticulum microsomes from AoB animals, 100 nmol/L istaroxime normalized the depressed (-32%) SERCA2a maximum velocity and increased SERCA activity (+17%). In muscle strips from hearts from patients undergoing cardiac transplantation, istaroxime (0.1-1.0 micromol/L) increased (in a concentration-dependent manner) developed tension, the maximum and minimum first derivative of tension, and absolute velocity of contraction, while stimulating SERCA activity in sarcoplasmic reticulum microsomes at physiologic free calcium concentrations. In conclusion, istaroxime is presently the only available compound that stimulates SERCA2a activity and produces a luso-inotropic effect in HF.
-
The customary interpretation of active-controlled noninferiority trials is founded on a number of unverifiable assumptions. These assumptions can be circumvented, and the semantic and statistic interpretation of the trials placed on a more rational foundation, if treatment comparisons are analyzed from a Bayesian perspective. In conclusion, the resultant probabilistic measures thereby render the meaning of noninferiority more transparent and clinically relevant.
-
In recent years, bariatric surgery has become an increasingly used therapeutic option for morbid obesity. The effect of weight loss after bariatric surgery on the predicted risk of coronary heart disease (CHD) has not previously been studied. We evaluated baseline (preoperative) and follow-up (postoperative) body mass index, CHD risk factors, and Framingham risk scores (FRSs) for 109 consecutive patients with morbid obesity who lost weight after laparoscopic Roux-en-Y gastric bypass surgery. ⋯ In conclusion, weight loss results in a significant decrease in FRS 10-year predicted CHD risk. Bariatric surgery decreases CHD risk to rates lower than the age- and gender-adjusted estimates for the general population. These data suggest substantial and sustained weight loss after bariatric surgery may be a powerful intervention to decrease future rates of myocardial infarction and death in the morbidly obese.
-
This study compared different measurements of repolarization duration in patients after infarction with and without conduction disturbances and evaluated the prognostic significance of repolarization parameters for predicting mortality in patients with conduction abnormalities. The study population consisted of 3,282 patients after recent myocardial infarction. Repolarization duration was measured using Bazett QTc and JTc (QTc minus QRS) and Rautaharju QT and JT(RR) formulas. ⋯ Repolarization parameters were uniformly dichotomized at the 75th percentile (QTc interval >490 ms, JTc interval >360 ms, QT(RR,QRS) interval >433 ms, JT(RR) interval >359 ms) to determine their prognostic significance for predicting mortality. After adjustment for significant clinical predictors of mortality, the hazard ratios were 1.65 for QTc interval (p = 0.062), 1.46 for JTc interval (p = 0.168), 1.71 for QT(RR,QRS) interval (p = 0.043), and 1.70 for JT(RR) interval (p = 0.044)(.) In conclusion, patients with left bundle branch block, right bundle branch block, or indeterminate ventricular conduction disturbances show longer repolarization duration than patients without these conduction disturbances, and QT(RR,QRS) and JT(RR) intervals reflect better than QTc repolarization duration in patients with conduction disturbances. QT(RR) and JT(RR) intervals significantly and independently predict mortality in patients after infarction with conduction disturbances.
-
Multicenter Study
Possible gender-related differences in the risk-to-benefit ratio of thrombolysis for acute submassive pulmonary embolism.
The indications for thrombolytic treatment in normotensive patients with pulmonary embolism (PE) are still the subject of debate, and it also remains questionable whether the efficacy and safety of thrombolysis are similar in men and women. To address the latter issue, the present study analyzed a large population of 428 women and 291 men with acute submassive PE derived from a prospective multicenter registry. Initial treatment consisted either of thrombolysis (<24 hours after diagnosis) or heparin alone. ⋯ Gender-specific differences were also observed with regard to the reduction of symptomatic PE recurrence (in men, from 21.6% to 8.2%, p = 0.009; in women, from 16.9% to 8.3%, p = 0.049). In contrast, thrombolysis resulted in a more than threefold increase in major bleeding in women (from 8.4% to 27.1%, p <0.001), a more pronounced effect than in men (from 6.9% to 15.1%, p = 0.055). In conclusion, the present study generated the hypothesis that women with submassive PE might benefit less from thrombolytic treatment in terms of survival and PE recurrence and that they could be exposed to a higher bleeding risk compared with men.