Short-Term Effects of Tolvaptan in Patients With Acute Heart Failure and Volume Overload.

BACKGROUND: In patients with acute heart failure (AHF), dyspnea relief is the most immediate goal. Renal dysfunction, diuretic resistance, and hyponatremia represent treatment impediments. OBJECTIVES: It was hypothesized that the addition of tolvaptan to a background diuretic improved dyspnea early in patients selected for an enhanced vasopressin antagonism response. METHODS: In a double-blind trial, patients were randomized to tolvaptan 30 mg/day or placebo. Study entry required hospitalization within the previous 36 h, active dyspnea, and any of the following: 1) estimated glomerular filtration rate <60 ml/min/1.73 m2; 2) hyponatremia; or 3) diuretic resistance (urine output ≤125 ml/h following intravenous furosemide ≥40 mg). The primary endpoint was a 7-point change in self-assessed dyspnea at 8 and 16 h, using a novel standardized approach. RESULTS: We randomized 250 patients. There was no difference in the primary endpoint of day 1 dyspnea reduction, despite significantly greater weight reduction with tolvaptan (-2.4 ± 2.1 kg vs. -0.9 ± 1.8 kg; p < 0.001). At day 3, dyspnea reduction was greater with tolvaptan (p = 0.01). There were 2 significant treatment-by-subgroup interactions: patients without elevated jugular venous pressure and those without ascites showed directional favorability of tolvaptan over placebo for the primary endpoint compared with patients with these findings. CONCLUSIONS: Despite rapid and persistent weight loss with tolvaptan compared with placebo, in patients with AHF who were selected for greater potential benefit from vasopressin receptor inhibition, tolvaptan was not associated with greater early improvement in dyspnea. Apparent subsequent differences in dyspnea warrant further exploration of the temporal relationship between diuresis and dyspnea relief and a possible clinical role for tolvaptan. (Randomized, Double-Blind, Placebo Controlled Study of the Short Term Clinical Effects of Tolvaptan in Patients Hospitalized for Worsening Heart Failure With Challenging Volume Management [SECRET of CHF]; NCT01584557).

Coronary computed tomography angiography predicts subsequent cardiac outcome events: results of the Visipaque CCTA registry study.

OBJECTIVES: To evaluate the diagnostic performance and predictive value of coronary computed tomography angiography (CCTA) on subsequent cardiac outcomes. BACKGROUND: CCTA has been suggested as an alternative method to invasive coronary angiography for detection of and ruling out coronary artery disease (CAD). However, the usefulness of CCTA findings in predicting patient outcome in routine clinical practice is still uncertain. MATERIALS AND METHODS: A prospective, multicenter registry study of CCTA with a Visipaque injection 320 mg I/ml was carried out in symptomatic patients suspected of having CAD as part of their medical care. CCTA findings were used to guide patient management decisions. Patient cardiac outcomes were followed at 1, 6, and 12 months after the CCTA procedure for the occurrence of major adverse cardiac event (MACE) (cardiac death, nonfatal myocardial infarction, or unstable angina requiring hospitalization). All cardiac outcome events or deaths were adjudicated independently. RESULTS: Of 874 patients (mean age=59 years; 51% men) who received Visipaque, 857 were included in the efficacy analysis. Using cardiac outcomes as the endpoint, the sensitivity of CCTA was 96.1, 95.8, and 94.7%, specificity was 84.5, 86.6, and 87.0%, and negative predictive value more than 99.0% at 1, 6, and 12 months, respectively. At 12 months, the rate of MACE was 5.7% (10/174) in patients with a positive CCTA (one or more ≥50% stenosis) and 0.1% (1/683) in patients with a negative CCTA (99.9% MACE-free survival rate). The Cox proportional hazards analysis with CCTA outcome, age, sex, reasons for CCTA, and cardiac risk factors as covariates showed a hazard ratio of 87.6 for positive versus negative CCTA (P=0.0001). CONCLUSION: CCTA is a highly accurate, noninvasive tool to detect or rule out subsequent cardiovascular events in patients with intermediate pretest probability of CAD or an uninterpretable/equivocal stress test. A positive CCTA finding contributed significantly toward the prediction of subsequent MACE whereas a negative CCTA carried excellent prognostic outcomes at 12 months.