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

Successful Treatment with S-1 and Oxaliplatin Combination Therapy in an Elderly Patient with Metastatic Colorectal Cancer Initially Presenting with Membranous Nephropathy

The incidence, morbidity, and mortality of colorectal cancer are increasing, largely owing to an increasingly aging population. Additionally, along with the increasing age of cancer patients, the number of patients with various comorbidities such as membranous nephropathy is also rising, and problems associated with the administration of chemotherapy to elderly patients with these conditions are becoming more common. Herein, we describe a case involving an 80-year-old woman who presented with general malaise, edematous limbs, and pleural effusion. An abdominal CT revealed multiple, relatively large, metastatic lesions in a wide area of the liver and left pleural effusion, and she was accordingly diagnosed with membranous nephropathy secondary to ascending colon cancer and multiple liver metastases. Despite her advanced age and the presence of membranous nephropathy, her general condition was favorable and chemotherapy was hence administered. Taking the toxicity profiles and the patient's preference into consideration, S-1 and oxaliplatin (SOX) therapy was selected, which showed a good tolerability. An abdominal CT after 8 cycles of SOX therapy revealed a marked reduction in the metastatic lesions in the liver and a decrease in the left pleural effusion, and the levels of tumor markers also decreased (partial response). At the latest follow-up, after the completion of 16 cycles, the condition of the patient remained stable, without any apparent signs of progressive disease. Based on this case, we conclude that, even for elderly patients with systemic complications or comorbid diseases, standard treatments should be considered after their general conditions, and therapeutic regimens have been sufficiently examined

Morphological Properties of Atrial Fibrillation Waves in Patients with Left Ventricular Dysfunction—Spectral Analysis of Atrial Fibrillation Waves in Dilated Cardiomyopathy—

AbstractIntroduction: Although the atrial fibrillation cycle length (FCL) is considered to shorten in persistent atrial fibrillation (AF) as a result of electrical remodeling, whether a long-term change remains in FCL in patients with left ventricular (LV) dysfunction is uncertain. Morphological properties of AF waves were analyzed in patients with dilated cardiomyopathy (DCM). Methods and Results: The study population consisted of 43 patients with persistent AF, and they were divided into a DCM group (n = 14) and a control group (n = 29). Fibrillation waves from surface ECG lead V1 were purified by subtracting the QRS-T complex template. Power spectral analysis was performed by Fast Fourier Transformation, and the mean FCL was determined by the peak power frequency in 20 epochs at each recording. The LV ejection fraction was lower in the DCM group (50 ± 18%) than the control (63 ± 8%, p = 0.001). The mean FCL was shorter in the DCM group (132 ± 14 ms) than the control (151 ± 23 ms, p = 0.007) and there was a significant correlation between the FCL and LV dimensions (p = 0.03). Conclusion: In patients with persistent AF and LV dysfunction, FCL was shorter in comparison with the control, and seemed to be influenced by LV dimensions