Electrocardiographic characteristics in patients with heart failure and normal ejection fraction: a systematic review and meta‐analysis

Background: Little is known about ECG abnormalities in patients with heart failure and normal ejection fraction (HeFNEF) and how they relate to different etiologies or outcomes. Methods and Results: We searched the literature for peer‐reviewed studies describing ECG abnormalities in HeFNEF other than heart rhythm alone. Thirty five studies were identified and 32,006 participants. ECG abnormalities reported in patients with HeFNEF include atrial fibrillation (prevalence 12%–46%), long PR interval (11%–20%), left ventricular hypertrophy (LVH, 10%–30%), pathological Q waves (11%–18%), RBBB (6%–16%), LBBB (0%–8%), and long JTc (3%–4%). Atrial fibrillation is more common in patients with HeFNEF compared to those with heart failure and reduced ejection fraction (HeFREF). In contrast, long PR interval, LVH, Q waves, LBBB, and long JTc are more common in patients with HeFREF. A pooled effect estimate analysis showed that QRS duration ≥120 ms, although uncommon (13%–19%), is associated with worse outcomes in patients with HeFNEF. Conclusions: There is high variability in the prevalence of ECG abnormalities in patients with HeFNEF. Atrial fibrillation is more common in patients with HeFNEF compared to those with HeFREF. QRS duration ≥120 ms is associated with worse outcomes in patients with HeFNEF. Further studies are needed to address whether ECG abnormalities correlate with different phenotypes in HeFNEF

Resonant leptogenesis in a predictive SO(10) grand unified model

An SO(10) grand unified model considered previously by the authors featuring lopsided down quark and charged lepton mass matrices is successfully predictive and requires that the lightest two right-handed Majorana neutrinons be nearly degenerate in order to obtain the LMA solar neutrino solution. Here we use this model to test its predictions for baryogenesis through resonant-enhanced leptogenesis. With the conventional type I seesaw mechanism, the best predictions for baryogenesis appear to fall a factor of three short of the observed value. However, with a proposed type III seesaw mechanism leading to three pairs of massive pseudo-Dirac neutrinos, resonant leptogenesis is decoupled from the neutrino mass and mixing issues with successful baryogenesis easily obtained.Comment: 22 pages including 1 figure; published version with reference adde

Assessment of variation in immunosuppressive pathway genes reveals TGFBR2 to be associated with prognosis of estrogen receptor-negative breast cancer after chemotherapy

Introduction: Tumor lymphocyte infiltration is associated with clinical response to chemotherapy in estrogen receptor (ER) negative breast cancer. To identify variants in immunosuppressive pathway genes associated with prognosis after adjuvant chemotherapy for ER-negative patients, we studied stage I-III invasive breast cancer patients of European ancestry, including 9,334 ER-positive (3,151 treated with chemotherapy) and 2,334 ER-negative patients (1,499 treated with chemotherapy). Methods: We pooled data from sixteen studies from the Breast Cancer Association Consortium (BCAC), and employed two independent studies for replications. Overall 3,610 single nucleotide polymorphisms (SNPs) in 133 genes were genotyped as part of the Collaborative Oncological Gene-environment Study, in which phenotype and clinical data were collected and harmonized. Multivariable Cox proportional hazard regression was used to assess genetic associations with overall survival (OS) and breast

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