Nishimura, Rick

Background Chronic kidney disease ( CKD ) remains an independent predictor of cardiovascular morbidity and mortality. CKD complicates referral for percutaneous coronary intervention ( PCI ) in non–ST‐segment–elevation myocardial infarction ( NSTEMI ) patients because of the risk for acute kidney injury and the need for dialysis, with American College of Cardiology/American Heart Association guidelines underscoring the limited data on these patients. Methods and Results Using the National Inpatient Sample to analyze hospitalizations in the United States from 2004 to 2014, we sought to assess PCI utilization and in‐hospital outcomes in NSTEMI admissions with CKD . NSTEMI admissions were identified by International Classification of Diseases, Ninth Edition, Clinical Modification (ICD‐9‐CM) code 410.7. CKD admissions were identified by ICD‐9‐CM code 585. Propensity score–matched cohorts of patients with NSTEMI were matched for age, sex, comorbidities, race, median household income, primary payer status, and hospital characteristics. Of 4 488 795 hospitalizations for NSTEMI , 31% underwent PCI . Overall, 89% of admissions had no CKD . In addition, 32% of NSTEMI admissions with no CKD and 23%, 14%, and 22% with CKD stages 3, 4, and 5 underwent PCI , respectively. Hospitalized NSTEMI patients with CKD stages 4 and 5 had 41% and 20% less likelihood, respectively, of undergoing PCI compared with those with no CKD . Among hospitalized NSTEMI patients with no CKD or CKD stage 3, 4, or 5, PCI ‐treated groups had 63%, 57%, 39%, and 59% lower likelihood, respectively, of all‐cause, in‐hospital mortality compared with propensity score–matched medically managed groups. Conclusions PCI use decreased among hospitalized NSTEMI patients as CKD severity increased, and all‐cause, in‐hospital mortality was greater for NSTEMI patients admitted with more severe CKD regardless of treatment strategy.

Objective Female sex is a known risk factor for cardiac surgery, and tricuspid valve (TV) disease is more common in women. There are few data on sex-stratified surgical outcomes for isolated TV surgery. An administrative database was used to compare acute in-hospital outcomes between men and women undergoing isolated TV surgery. Methods Patients aged >18 who underwent TV repair or replacement from 2004 to 2013 were identified using the National Inpatient Sample. Patients were excluded if they had congenital heart disease, endocarditis, or were undergoing concomitant cardiac surgeries except coronary bypass. Results were weighted to represent national averages. Sex-stratified analysis was performed using propensity score matching to compare in-hospital mortality, postoperative complications and hospital costs. Results Over 10 years, women represented 58% of the 5005 TV surgeries performed. With propensity matching, hospital mortality (7.9% vs 7.7%; P=0.99) and median length of stay (11 vs 11 days; P=0.99) were similar between men and women. However, median hospital charges were higher for men ($166 000 vs $155 000; P=0.04). Conclusion Isolated TV surgery is rare, but women more commonly undergo the procedure. In-hospital mortality was similar between men and women after propensity matching, but remains markedly high for both men and women in comparison to that reported for left-sided isolated valve surgery.

Approximately half of patients with heart failure have preserved ejection fraction. There is no proven treatment that improves outcome. The pathophysiology of heart failure with preserved ejection fraction is complex and includes left ventricular systolic and diastolic dysfunction, pulmonary vascular disease, endothelial dysfunction, and peripheral abnormalities. Multiple lines of evidence point to impaired nitric oxide (NO)-cGMP bioavailability as playing a central role in each of these abnormalities. In contrast to traditional organic nitrate therapies, an alternative strategy to restore NO-cGMP signaling is via inorganic nitrite. Inorganic nitrite, previously considered to be an inert byproduct of NO metabolism, functions as an important in vivo reservoir for NO generation, particularly under hypoxic and acidosis conditions. As such, inorganic nitrite becomes most active at times of greater need for NO signaling, as during exercise when left ventricular filling pressures and pulmonary artery pressures increase. Herein, we present the rationale and design for the INDIE-HFpEF trial (Inorganic Nitrite Delivery to Improve Exercise Capacity in Heart Failure with Preserved Ejection Fraction), which is a multicenter, randomized, double-blind, placebo-controlled cross-over study assessing the effect of inhaled inorganic nitrite on peak exercise capacity, conducted in the National Heart, Lung, and Blood Institute–sponsored Heart Failure Clinical Research Network. Clinical Trial Registration URL: http://www.clinicaltrials.gov . Unique identifier: NCT02742129.

Background: Heart failure (HF) with preserved ejection fraction (HFpEF) is a heterogeneous syndrome. Phenotyping patients into pathophysiologically homogeneous groups may enable better targeting of treatment. Obesity is common in HFpEF and has many cardiovascular effects, suggesting that it may be a viable candidate for phenotyping. We compared cardiovascular structure, function, and reserve capacity in subjects with obese HFpEF, those with nonobese HFpEF, and control subjects. Methods: Subjects with obese HFpEF (body mass index ≥35 kg/m 2 ; n=99), nonobese HFpEF (body mass index <30 kg/m 2 ; n=96), and nonobese control subjects free of HF (n=71) underwent detailed clinical assessment, echocardiography, and invasive hemodynamic exercise testing. Results: Compared with both subjects with nonobese HFpEF and control subjects, subjects with obese HFpEF displayed increased plasma volume (3907 mL [3563–4333 mL] versus 2772 mL [2555–3133 mL], and 2680 mL [2380–3006 mL]; P <0.0001), more concentric left ventricular remodeling, greater right ventricular dilatation (base, 34±7 versus 31±6 and 30±6 mm, P =0.0005; length, 66±7 versus 61±7 and 61±7 mm, P <0.0001), more right ventricular dysfunction, increased epicardial fat thickness (10±2 versus 7±2 and 6±2 mm; P <0.0001), and greater total epicardial heart volume (945 mL [831–1105 mL] versus 797 mL [643–979 mL] and 632 mL [517–768 mL]; P <0.0001), despite lower N-terminal pro-B-type natriuretic peptide levels. Pulmonary capillary wedge pressure was correlated with body mass and plasma volume in obese HFpEF ( r =0.22 and 0.27, both P <0.05) but not in nonobese HFpEF ( P ≥0.3). The increase in heart volumes in obese HFpEF was associated with greater pericardial restraint and heightened ventricular interdependence, reflected by increased ratio of right- to left-sided heart filling pressures (0.64±0.17 versus 0.56±0.19 and 0.53±0.20; P =0.0004), higher pulmonary venous pressure relative to left ventricular transmural pressure, and greater left ventricular eccentricity index (1.10±0.19 versus 0.99±0.06 and 0.97±0.12; P <0.0001). Interdependence was enhanced as pulmonary artery pressure load increased ( P for interaction <0.05). Compared with those with nonobese HFpEF and control subjects, obese patients with HFpEF displayed worse exercise capacity (peak oxygen consumption, 7.7±2.3 versus 10.0±3.4 and12.9±4.0 mL/min·kg; P <0.0001), higher biventricular filling pressures with exercise, and depressed pulmonary artery vasodilator reserve. Conclusions: Obesity-related HFpEF is a genuine form of cardiac failure and a clinically relevant phenotype that may require specific treatments.

Abstract Aims Short-term studies have reported left ventricular (LV) dilatation following surgical creation of arteriovenous fistulas (AVF) or arteriovenous grafts (AVGs), but chronic cardiac structural and functional changes have not been examined or related to clinical outcomes following AVF/AVG. We sought to characterize the long-term changes in cardiac structure and function in patients undergoing shunt creation for haemodialysis. Methods and results A retrospective analysis was performed of patients undergoing echocardiography before and after surgical AVF/AVG creation for the initiation of haemodialysis. 137 patients underwent echocardiographic examinations prior to AVF and 2.6 years (median) after AVF creation. Following AVF and dialysis initiation, there were reductions in blood pressure, body weight and estimated plasma volume coupled with modest reverse LV remodelling. In contrast, AVF/AVG creation was associated with significant right ventricular (RV) dilatation and deterioration in RV function. Incident heart failure (HF) developed in 43% of patients in tandem with greater RV remodeling. The development of RV dilation following surgical AVF/AVG was independently associated with increased risk of death [HR 3.9, 95% CI (1.7–9.2), P = 0.001]. Conclusion In long-term follow-up, RV remodelling and dysfunction develop following AVF/AVG creation and dialysis initiation, despite improved control of LV pressure load through dialysis. Deleterious effects on right heart structure and function are coupled with development of incident HF and increased risk of death. Further study is required to identify patients at greatest risk for detrimental AVF/AVG changes who may benefit from alternate forms of dialysis or potentially ligation of existing AVF.