Coronary perfusion pressure is associated with adverse outcomes in advanced heart failure.

BACKGROUND: Myocardial perfusion is an important determinant of cardiac function. We hypothesized that low coronary perfusion pressure (CPP) would be associated with adverse outcomes in heart failure. Myocardial perfusion impacts the contractile efficiency thus a low CPP would signal low myocardial perfusion in the face of increased cardiac demand as a result of volume overload. METHODS: We analyzed patients with complete hemodynamic data in the Evaluation Study of Congestive Heart Failure and Pulmonary Artery Catheterization Effectiveness trial using Cox Proportional Hazards regression for the primary outcome of the composite risk of death, heart transplantation, or left ventricular assist device [(LVAD). DT × LVAD] and the secondary outcome of the composite risk of DT × LVAD and heart failure hospitalization (DT × LVADHF). CPP was calculated as the difference between diastolic blood pressure and pulmonary artery wedge pressure. Heart failure categories (ischemic vs non-ischemic) were also stratified based on CPP strata. RESULTS: The 158 patients (56.7 ± 13.6 years, 28.5% female) studied had a median CPP of 40 mmHg (IQR 35-52 mmHg). During 6 months of follow-up, 35 (22.2%) had the composite primary outcome and 109 (69.0%) had the composite secondary outcome. When these outcomes were then stratified based on the median, CPP was associated with these outcomes. Increasing CPP was associated with lower risk of both the primary outcome of DT × LVAD (HR 0.96, 95% CI 0.94-0.99 p = .002) and as well as the secondary outcome of DT × LVADHF (p = .0008) There was significant interaction between CPP and ischemic etiology (p = .04). CONCLUSION: A low coronary artery perfusion pressure below (median) 40mmHg in patients with advanced heart failure undergoing invasive hemodynamic monitoring with a pulmonary artery catheter was associated with adverse outcomes. CPP could useful in guiding risk stratification of advanced heart failure patients and timely evaluation of advanced heart failure therapies.

A systemic congestive index (systemic pulse pressure to central venous pressure ratio) predicts adverse outcomes in patients undergoing valvular heart surgery.

BACKGROUND AND AIMS: Invasive hemodynamics may provide a more nuanced assessment of cardiac function and risk phenotyping in patients undergoing cardiac surgery. The systemic pulse pressure (SPP) to central venous pressure (CVP) ratio represents an integrated index of right and left ventricular function and thus may demonstrate an association with valvular heart surgery outcomes. This study hypothesized that a low SPP/CVP ratio would be associated with mortality in valvular surgery patients. METHODS: This retrospective cohort study examined adult valvular surgery patients with preoperative right heart catheterization from 2007 through 2016 at a single tertiary medical center (n = 215). Associations between the SPP/CVP ratio and mortality were investigated with univariate and multivariate analyses. RESULTS: Among 215 patients (age 69.7 ± 12.4 years; 55.8% male), 61 died (28.4%) over a median follow-up of 5.9 years. A SPP/CVP ratio <7.6 was associated with increased mortality (relative risk 1.70, 95% confidence interval [CI] 1.08-2.67, p = .019) and increased length of stay (11.56 ± 13.73 days vs. 7.93 ± 4.92 days, p = .016). It remained an independent predictor of mortality (adjusted odds ratio 3.99, 95% CI 1.47-11.45, p = .008) after adjusting for CVP, mean pulmonary artery pressure, aortic stenosis, tricuspid regurgitation, smoking status, diabetes mellitus, dialysis, and cross-clamp time. CONCLUSIONS: A low SPP/CVP ratio was associated with worse outcomes in patients undergoing valvular heart surgery. This metric has potential utility in preoperative risk stratification to guide patient selection, prognosis, and surgical outcomes.

Increased left and right atrial volume indices are associated with decreased survival times post-cardiac arrest.

BACKGROUND: Left and right atrial volume indices (LAVI and RAVI) are markers of cardiac remodeling. LAVI and RAVI are associated with worse outcomes in other cardiac conditions. This study aimed to determine the associations of these atrial volume indices with survival time post-cardiac arrest. METHODS: This was a single center, retrospective study of patients with a sudden cardiac arrest event during index hospitalization from 2014-2018 based on pre-arrest parameters. The analysis was stratified based on whether a pulseless ventricular tachycardia/ventricular fibrillation (pVT/VF) event or a pulseless electrical activity (PEA)/asystole event occurred. Cox proportional hazards regression and model selection with best subsets approach evaluated the association of atrial volume parameters with survival times in the context of other covariates. RESULTS: Of 305 patients studied (64 ± 14 years, 37% female), the mean LAVI was 34.0 ± 15.8 mL/m2 (based on 162 reliable measurements), and mean RAVI was 25.0 ± 15.6 mL/m2 (based on 163 measurements). Increased atrial volume indices were most strongly associated with survival in patients who had sustained pVT/VF (LAVI HR 0.47, 95% CI 0.25-0.90, p = 0.020; RAVI HR 0.57, 95% CI 0.30-1.05, p = 0.074). In multivariable best subsets Cox regression with LAVI, RAVI, and 13 other scaled covariates, LAVI < 34 ml/m2 was by far the best single predictor of survival (p < 0.0001), and the next best predictor was the absence of pulmonary hypertension. CONCLUSION: Among patients with cardiac arrest from ventricular arrhythmias, those with no more than mild left atrial enlargement pre-arrest by LAVI measurement had the best prognosis. Additional studies are indicated to validate the importance of this finding for clinical management decisions. CONDENSED ABSTRACT: In patients with sudden cardiac arrest associated with ventricular arrhythmias, a left atrial volume index (LAVI) < 34 mL/m2 prior to the arrest had the strongest association with survival among fifteen candidate predictors. Pulmonary hypertension was more common in patients with an elevated right atrial volume index (RAVI), and the absence of pulmonary hypertension was the next best pre-arrest parameter predictive of survival. Larger studies are indicated to validate the use of LAVI for clinical management decisions in this condition.

Targeting a Single Alternative Polyadenylation Site Coordinately Blocks Expression of Androgen Receptor mRNA Splice Variants in Prostate Cancer.

Prostate cancer is the second leading cause of male cancer deaths due to disease progression to castration-resistant prostate cancer (CRPC). Androgen receptor (AR) splice variants including AR-V7 function as constitutively active transcription factors in CRPC cells, thereby promoting resistance to AR-targeted therapies. To date, there are no AR variant-specific treatments for CRPC. Here we report that the splicing of AR variants AR-V7 as well as AR-V1 and AR-V9 is regulated coordinately by a single polyadenylation signal in AR intron 3. Blocking this signal with morpholino technology or silencing of the polyadenylation factor CPSF1 caused a splice switch that inhibited expression of AR variants and blocked androgen-independent growth of CRPC cells. Our findings support the development of new therapies targeting the polyadenylation signal in AR intron 3 as a strategy to prevent expression of a broad array of AR variants in CRPC. Cancer Res; 77(19); 5228-35. ©2017 AACR.