Omecamtiv mecarbil in chronic heart failure with reduced ejection fraction, GALACTIC‐HF: baseline characteristics and comparison with contemporary clinical trials

Aims: The safety and efficacy of the novel selective cardiac myosin activator, omecamtiv mecarbil, in patients with heart failure with reduced ejection fraction (HFrEF) is tested in the Global Approach to Lowering Adverse Cardiac outcomes Through Improving Contractility in Heart Failure (GALACTIC‐HF) trial. Here we describe the baseline characteristics of participants in GALACTIC‐HF and how these compare with other contemporary trials. Methods and Results: Adults with established HFrEF, New York Heart Association functional class (NYHA) ≥ II, EF ≤35%, elevated natriuretic peptides and either current hospitalization for HF or history of hospitalization/ emergency department visit for HF within a year were randomized to either placebo or omecamtiv mecarbil (pharmacokinetic‐guided dosing: 25, 37.5 or 50 mg bid). 8256 patients [male (79%), non‐white (22%), mean age 65 years] were enrolled with a mean EF 27%, ischemic etiology in 54%, NYHA II 53% and III/IV 47%, and median NT‐proBNP 1971 pg/mL. HF therapies at baseline were among the most effectively employed in contemporary HF trials. GALACTIC‐HF randomized patients representative of recent HF registries and trials with substantial numbers of patients also having characteristics understudied in previous trials including more from North America (n = 1386), enrolled as inpatients (n = 2084), systolic blood pressure < 100 mmHg (n = 1127), estimated glomerular filtration rate < 30 mL/min/1.73 m2 (n = 528), and treated with sacubitril‐valsartan at baseline (n = 1594). Conclusions: GALACTIC‐HF enrolled a well‐treated, high‐risk population from both inpatient and outpatient settings, which will provide a definitive evaluation of the efficacy and safety of this novel therapy, as well as informing its potential future implementation

Concomitant cat scratch disease and squamous cell carcinoma in a cardiac transplant

Cat scratch disease has been reported very rarely in cardiac transplant recipients. In a review of 1073 episodes of infection in 620 heart transplant patients over a 16 year period, only one case of infection secondary to Bartonella henselae was documented. Another case of hepatosplenic bacillary angiomatosis from B. henselae was reported 2 decades ago in a heart transplant recipient who had presented with fevers of unknown origin. Although the typical clinical manifestation is that of a skin lesion accompanied with lymphadenopathy, cat scratch disease may present with persistent fevers without a clinically overt infective focus in immunosuppressed individuals. Moreover, more than one disease process may coexist in immunocompromised hosts. While the lymphadenopathy in our patient was secondary to Cat scratch disease, interestingly, the adjacent skin lesion that was thought to represent unhealed site of inoculation of Bartonella was diagnosed as squamous cell carcinoma

Antigenic stimulation in the simian model of HIV infection yields dilated cardiomyopathy through effects of TNFalpha

OBJECTIVE: To investigate a role for endogenous myocardial cytokine production in the development of HIV-associated cardiomyopathy. DESIGN: Cardiomyopathy is a late-stage sequela of HIV infection. Although pathogenesis of this condition in HIV infection is poorly defined, inflammatory cytokines are recognized for their detrimental effects on myocardial structure and function. HIV infection is characterized by chronic immune activation and inflammatory cytokine dysregulation. As the myocardium itself is a rich potential source of inflammatory cytokines, HIV-mediated cytokine dysregulation may be an important contributor to development of HIV cardiomyopathy. An antigenic stimulation protocol conducted in the simian immunodeficiency virus (SIV) model of HIV infection was used to study the effects of endogenous cytokine production on myocardial structure and function. METHODS: Twenty-six rhesus monkeys were assigned to treatment groups for a 35-day study. Animals were SIV-infected; SIV-infected and treated with killed Mycobacterium avium complex bacteria (MAC); SIV-infected, MAC-treated, and given the TNFalpha antagonist etanercept; or uninfected and MAC-treated. All animals were subjected to weekly echocardiographic studies. Hearts were collected for further evaluation at euthanasia. RESULTS: SIV-infected, MAC-treated animals developed significant systolic dysfunction [left ventricular ejection fraction (LVEF) decline of 19 +/- 2%] and ventricular chamber dilatation [left ventricular end-diastolic diameter (LVEDD) increase of 26 +/- 6%] not seen in other groups. Concurrent treatment with etanercept prevented development of these changes, implicating a causative role of myocardial TNFalpha. CONCLUSIONS: SIV-infected animals develop exaggerated myocardial pathology on stimulation with the ubiquitous environmental agent MAC. These responses are TNFalpha-dependent and may play a significant role in the development of cardiomyopathy in HIV infection

Effect of glucagon-like peptide-1 (GLP-1) on glycemic control and left ventricular function in patients undergoing coronary artery bypass grafting.

Increasing evidence suggests that tight glycemic control improves clinical outcomes after coronary artery bypass grafting (CABG). However, the risk for hypoglycemia with insulin often results in less aggressive glycemic control. Glucagon-like peptide-1 (GLP-1) is a naturally occurring peptide whose insulinotropic effects are predicated on the glucose concentration, minimizing the risk for hypoglycemia. This study was conducted to examine whether perioperative treatment with GLP-1 would affect glycemic control and improve hemodynamic recovery after CABG. Twenty patients with coronary heart disease and preserved left ventricular function who were scheduled to undergo CABG were randomized to receive standard therapy at the discretion of the surgeon or treatment with GLP-1 (1.5 pmol/kg/min) as a continuous infusion beginning 12 hours before CABG and continuing for 48 hours. Perioperative hemodynamics, the left ventricular ejection fraction, plasma glucose, and requirements for insulin drips and inotropic support were monitored. There were no differences between groups in the preoperative, postoperative, or 7-day left ventricular ejection fraction (GLP-1 61 +/- 4%, control 59 +/- 3%) or cardiac index at 18 hours (GLP-1 3.0 +/- 0.2 L/min/m(2), control 3.3 +/- 0.4 L/min/m(2)). However, the control group required greater use of inotropic and vasoactive infusions during the 48 hours after the operation to achieve the same hemodynamic result. There were also more frequent arrhythmias requiring antiarrhythmic agents in the control group. GLP-1 resulted in better glycemic control in the pre- and perioperative periods (GLP-1 95 +/- 3 mg/dl, control 140 +/- 10 mg/dl,