Prevalence and risk factors of prolonged QTc interval in HIV-infected patients: results of the HIV-HEART study.

BACKGROUND: Corrected QT (QTc) prolongation is predictive of cardiovascular mortality in both the general and human immunodeficiency virus (HIV) populations. OBJECTIVE: As part of the HIV-HEART study, we assessed the prevalence and risk factors of a prolonged QTc interval in patients with HIV infection. METHODS: In this cross-sectional cohort study, 802 unselected HIV-infected patients were included. Data were analyzed by the use of gender-specific QTc categories (men abnormal at > 440 ms and women abnormal at >460 ms). Multiple variables related to infection and treatment were collected. Results were analyzed with a multivariable model. RESULTS: The QTc interval was found to be prolonged in 154 patients (19.8%; 95% CI 17-23). The mean (+/-SD) QTc in men (n = 142) presenting with a prolonged QTc interval was 456 +/- 16.3 ms (range 441-548 ms). The mean (+/-SD) QTc in women (n = 12) presenting with a prolonged QTc interval was 479 +/- 9 ms (range 465-498 ms). In the multivariable model, female gender, diabetes mellitus, and arterial hypertension were associated with prolonged QTc. There were no parameters related to HIV independently associated with QT interval prolongation. In particular, no anti-HIV drug was associated with QTc prolongation. CONCLUSIONS: Our study demonstrated that in an HIV-infected population, QTc prolongation had a high prevalence of nearly 20% compared to the general population and was possibly influenced by common factors like gender, diabetes, and arterial hypertension.

Neurohumoral response and clinical effectiveness of continuous aortic flow augmentation in patients with decompensated heart failure.

The increasing number of patients with progressive or exacerbated heart failure that is refractory to medical treatment necessitates the development of innovative cardiac assist devices. The aim of this study was to investigate whether a new percutaneously inserted system, which allows continuous aortic flow augmentation (CAFA), could be shown to be clinically effective with neurohormonal benefit in patients admitted with decompensated heart failure. Patients with exacerbations of chronic heart failure were recruited for the study. A percutaneous circulation assist device (Cancion system) promoting CAFA was implanted for up to 4 days in each patient. Clinical improvement was evaluated by measuring the clinical status according to the New York Heart Association (NYHA) classification and biochemical parameters including troponin and B-type natriuretic peptide (BNP) as markers of cardiac necrosis and cardiac overload; these parameters were measured before, during, and after CAFA treatment. The decrease in BNP was determined after implantation, reaching, on average, a maximum decrease of 57% at 72 h (P = 0.04). The neurohumoral response remained significant (P < 0.05) up to 120 h after implantation, with a decrease in BNP levels of 37%, on average, compared to baseline values. Troponin I did not show any significant change during mechanical assistance (P > 0.2). All patients had improved clinical status according to the NYHA classification, and the improvement lasted for more than 1 week. Percutaneous heart-assist devices promoting CAFA offer clinical improvement and a neurohumoral response, with a significant BNP reduction in severe exacerbation of chronic heart failure that is refractory to medical treatment.

Bacterial DNA induces myocardial inflammation and reduces cardiomyocyte contractility: role of toll-like receptor 9.

AIMS: Myocardial function is severely compromised during sepsis. Several underlying mechanisms have been proposed. The innate immune system, i.e. toll-like receptor (TLR) 2 and 4, significantly contributes to cardiac dysfunction. Little is known regarding TLR9 and its pathogenic ligand bacterial DNA in the myocardium. We therefore studied the role of TLR9 in myocardial inflammation and cardiac contractility. METHODS AND RESULTS: Wild-type (WT, C57BL/6) and TLR9-deficient (TLR9-D) mice and isolated cardiomyocytes were challenged with synthetic bacterial DNA (CpG-ODN). Myocardial contractility as well as markers of inflammation/signalling were determined. Isolated cardiomyocytes incorporated fluorescence-marked CpG-ODN. In WT mice, CpG-ODN caused a robust response in hearts demonstrated by increased levels of tumour necrosis factor (TNF-alpha), interleukin (IL)-1beta, IL-6, inducible nitric oxide synthase (iNOS), and nuclear factor kappaB activity. This inflammatory response was absent in TLR9-D mice. Under similar conditions, contractility measurements of isolated ventricular cardiomyocytes demonstrated a TLR9-dependent loss of sarcomeric shortening after CpG-ODN exposure. This observation was iNOS dependent as the application of a specific iNOS inhibitor reversed sarcomeric shortening to normal levels. CONCLUSION: Our data suggest that bacterial DNA contributes to myocardial cytokine production and loss of cardiomyocyte contractility via TLR9.