Unanswered ethical and scientific questions for trials of invasive interventions for coronary disease: The case of single vessel disease

Trials in the 1990s demonstrated that medical therapy is as effective as invasive therapies for treating single-vessel coronary disease. Yet more recent studies enrolling patients with this condition have focused on evaluating only invasive approaches, namely, stenting versus coronary artery bypass surgery. Several ethical and scientific questions remain unanswered regarding the conduct of these later trials. Were they justified? Why wasn't a medical therapy arm included? Were subjects informed about the availability of medical therapy as an equivalent option? Was optimized medical therapy given prior to randomization? The absence of clear answers to these questions raises the possibility of serious bias in favor of invasive interventions. Considering that medical therapy is underutilized in patients with coronary disease, efforts should focus more on increasing utilization of medical therapy and proper selection of noninvasive interventions

Differential Prognostic Impact of Resting Heart Rate in Older Compared With Younger Patients With Chronic Heart Failure: Insights From TIME-CHF

Background: There is little information regarding the prognostic role of resting heart rate (HR) in older compared with younger patients with chronic heart failure (HF). Methods and Results: In patients enrolled in the Trial of Intensified Medical Therapy in Elderly Patients With Congestive Heart Failure (TIME-CHF) with sinus rhythm, effects of baseline HR (>= 70 vs = 75 years; n = 186) and younger ( Conclusions: In contrast to HF patients aged = 75 years

Circulating biomarkers of distinct pathophysiological pathways in heart failure with preserved vs. reduced left ventricular ejection fraction

Aims The aim of this study was to evaluate whether biomarkers reflecting pathophysiological pathways are different between heart failure with preserved (HFpEF) and reduced ejection fraction (HFrEF) and whether the prognostic value of biomarkers is different in HFpEF vs. HFrEF. Methods and resultsA total of 458 HFrEF (LVEF 40%) and 112 HFpEF (LVEF 50%) patients aged 60 years with NYHA class II from TIME-CHF were included. Endpoints are 18-month overall and HF hospitalization-free survival. After correction for baseline characteristics that differed between the HF types, i.e. age, gender, body mass index, systolic blood pressure, cause of HF, and AF, HFpEF patients exhibited higher soluble interleukin 1 receptor-like 1 [ST2; 37.6 (28.5-54.7) vs. 35.7 (25.6-52.2), P = 0.02], high sensitivity C-reactive protein (hsCRP; 8.54 (3.39-25.86) vs. 6.66 (2.42-15.39), P = 0.01), and cystatin-C [1.94 (1.57-2.37) vs. 1.75 (1.39-2.12), P = 0.01]. In contrast, HFrEF patients exhibited higher NT-proBNP [2142 (1473-4294) vs. 4202 (2239-7411), P 0.10 for both endpoints), except for cystatin-C which had less prognostic impact in HFpEF (P <0.01). ConclusionBiomarker levels suggest a different amount of activation of several pathophysiological pathways between HFpEF and HFrEF. No important differences in the prognostic value of biomarkers in HFpEF vs. HFrEF were found except for cystatin-C, and for NT-proBNP in the NT-proBNP-guided study arm only, both of which had less prognostic value in HFpEF. Trial registrationISRCTN4359647