Relationship of ejection fraction and natriuretic peptide trajectories in heart failure with baseline reduced and mid-range ejection fraction.

BACKGROUND: The prognostic importance of trajectories of neurohormones relative to left ventricular function over time in heart failure with reduced and mid-range EF (HFrEF and HFmrEF) is poorly defined. OBJECTIVE: To evaluate left ventricular ejection fraction (LVEF) and B-type natriuretic peptide (BNP) trajectories in HFrEF and HFmrEF. METHODS: Analyses of LVEF and BNP trajectories after incident HF admissions presenting with abnormal LV systolic function were performed using 3 methods: a Cox proportional hazards model with time-varying covariates, a dual longitudinal-survival model with shared random effects, and an unsupervised analysis to capture 3 discrete trajectories for each parameter. RESULTS: Among 1,158 patients (68.9 ± 13.0 years, 53.3% female), both time-varying LVEF measurements (P=.001) and log-transformed BNP measurements (p-values=2 × 10-16) were independently associated with survival during 6 years after covariate adjustment. In the dual longitudinal/survival model, both LVEF and BNP trajectories again were independently associated with survival (P<.0001 in each model); however, LVEF was more dynamic than BNP (P <.0001 for time covariate in LVEF longitudinal model versus P=.88 for the time covariate in BNP longitudinal model). In the unsupervised analysis, 3 discrete LVEF trajectories (dividing the cohort into approximately thirds) and 3 discrete BNP trajectories were identified. Discrete LVEF and BNP trajectories had independent prognostic value in Kaplan-Meier analyses (P<.0001), and substantial membership variability across BNP and LVEF trajectories was noted. CONCLUSION: Although LVEF trajectories have greater temporal variation, BNP trajectories provide additive prognostication and an even stronger association with survival times in heart failure patients with abnormal LV systolic function.

Pulmonary Artery Proportional Pulse Pressure (PAPP) Index Identifies Patients With Improved Survival From the CardioMEMS Implantable Pulmonary Artery Pressure Monitor.

BACKGROUND: Pulmonary artery proportional pulse pressure (PAPP) was recently shown to have prognostic value in heart failure (HF) with reduced ejection fraction (HFrEF) and pulmonary hypertension. We tested the hypothesis that PAPP would be predictive of adverse outcomes in patients with implantable pulmonary artery pressure monitor (CardioMEMS™ HF System, St. Jude Medical [now Abbott], Atlanta, GA, USA). METHODS: Survival analysis with Cox proportional hazards regression was used to evaluate all-cause deaths and HF hospitalisation (HFH) in CHAMPION trial1 patients who received treatment with the CardioMEMS device based on the PAPP. RESULTS: Among 550 randomised patients, 274 had PAPP ≤ the median value of 0.583 while 276 had PAPP>0.583. Patients with PAPP≤0.583 (versus PAPP>0.583) had an increased risk of HFH (HR 1.40, 95% CI 1.16-1.68, p=0.0004) and experienced a significant 46% reduction in annualised risk of death with CardioMEMS treatment (HR 0.54, 95% CI 0.31-0.92) during 2-3 years of follow-up. This survival benefit was attributable to the treatment benefit in patients with HFrEF and PAPP≤0.583 (HR 0.50, 95% CI 0.28-0.90, p<0.05). Patients with PAPP>0.583 or HF with preserved EF (HFpEF) had no significant survival benefit with treatment (p>0.05). CONCLUSION: Lower PAPP in HFrEF patients with CardioMEMS constitutes a higher mortality risk status. More studies are needed to understand clinical applications of PAPP in implantable pulmonary artery pressure monitors.

High-fat or ethinyl-oestradiol intake during pregnancy increases mammary cancer risk in several generations of offspring.

Maternal exposures to environmental factors during pregnancy influence the risk of many chronic adult-onset diseases in the offspring. Here we investigate whether feeding pregnant rats a high-fat (HF)- or ethinyl-oestradiol (EE2)-supplemented diet affects carcinogen-induced mammary cancer risk in daughters, granddaughters and great-granddaughters. We show that mammary tumourigenesis is higher in daughters and granddaughters of HF rat dams and in daughters and great-granddaughters of EE2 rat dams. Outcross experiments suggest that the increase in mammary cancer risk is transmitted to HF granddaughters equally through the female or male germ lines, but it is only transmitted to EE2 granddaughters through the female germ line. The effects of maternal EE2 exposure on offspring's mammary cancer risk are associated with changes in the DNA methylation machinery and methylation patterns in mammary tissue of all three EE2 generations. We conclude that dietary and oestrogenic exposures in pregnancy increase breast cancer risk in multiple generations of offspring, possibly through epigenetic means.