All experts involved in the development of these guidelines have submitted declarations of interest. These have been compiled in a report and published in a supplementary document simultaneously to the guidelines. The report is also available on the ESC website www.escardio.org/Guidelines See the European Heart Journal online for supplementary data that includes background information and detailed discussion of the data that have provided the basis of the guidelines.Click here to access the corresponding ESC CardioMed chapters.

BACKGROUNDThe selective cardiac myosin activator omecamtiv mecarbil has been shown to improve cardiac function in patients with heart failure with a reduced ejection fraction. Its effect on cardiovascular outcomes is unknown. METHODSWe randomly assigned 8256 patients (inpatients and outpatients) with symptomatic chronic heart failure and an ejection fraction of 35% or less to receive omecamtiv mecarbil (using pharmacokinetic-guided doses of 25 mg, 37.5 mg, or 50 mg twice daily) or placebo, in addition to standard heart-failure therapy. The primary outcome was a composite of a first heart-failure event (hospitalization or urgent visit for heart failure) or death from cardiovascular causes. RESULTSDuring a median of 21.8 months, a primary-outcome event occurred in 1523 of 4120 patients (37.0%) in the omecamtiv mecarbil group and in 1607 of 4112 patients (39.1%) in the placebo group (hazard ratio, 0.92; 95% confidence interval [CI], 0.86 to 0.99; P = 0.03). A total of 808 patients (19.6%) and 798 patients (19.4%), respectively, died from cardiovascular causes (hazard ratio, 1.01; 95% CI, 0.92 to 1.11). There was no significant difference between groups in the change from baseline on the Kansas City Cardiomyopathy Questionnaire total symptom score. At week 24, the change from baseline for the median N-terminal pro-B-type natriuretic peptide level was 10% lower in the omecamtiv mecarbil group than in the placebo group; the median cardiac troponin I level was 4 ng per liter higher. The frequency of cardiac ischemic and ventricular arrhythmia events was similar in the two groups. CONCLUSIONSAmong patients with heart failure and a reduced ejection, those who received omecamtiv mecarbil had a lower incidence of a composite of a heart-failure event or death from cardiovascular causes than those who received placebo.

GLS is an independent predictor of all-cause mortality in HFrEF patients, especially in male patients without AF. Furthermore, GLS was a superior prognosticator compared with all other echocardiographic parameters.

Background Asymptomatic individuals account for a majority of sudden cardiac deaths (SCDs). Development of effective, low-cost, and non-invasive SCD risk stratification tools are necessary. Methods and Results Participants from the Atherosclerosis Risk in Communities study and Cardiovascular Health Study (n=20,177; age 59.3±10.1 years; age range 44–100; 56% female; 77% white) were followed for 14.0 years (median). Five ECG markers of global electrical heterogeneity (GEH) (sum absolute QRST integral, spatial QRST angle, spatial ventricular gradient (SVG) magnitude, SVG elevation, and SVG azimuth) were measured on standard 12-lead ECGs. Cox proportional hazards and competing risks models evaluated associations between GEH ECG parameters and SCD. A SCD competing risks score was derived using demographics, comorbidities, and GEH parameters. SCD incidence was 1.86 per 1,000 person-years. After multivariable adjustment, baseline GEH parameters and large increases in GEH parameters over time were independently associated with SCD. Final SCD risk scores included age, sex, race, diabetes, hypertension, coronary heart disease, and stroke, and GEH parameters as continuous variables. When GEH parameters were added to clinical/demographic factors, the C-statistic increased from 0.777 to 0.790 (p=0.008), the risk score classified 10-year SCD risk as high (>5%) in 7.2% of participants, 10% of SCD victims were appropriately reclassified into a high-risk category, and only 1.4% of SCD victims were inappropriately reclassified from high- to intermediate-risk. Net reclassification index was 18.3%. Conclusions Abnormal electrophysiological substrate quantified by GEH parameters is independently associated with SCD in the general population. Addition of GEH parameters to clinical characteristics improves SCD risk prediction.

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