Maternal and Fetal Outcomes in Pulmonary Hypertension During Pregnancy: A Contemporary Nationwide Analysis.

Pulmonary hypertension (PH) disproportionately affects women, presenting challenges during pregnancy. Historically, patients with PH are advised to avoid pregnancy; however, recent reports have indicated that the incidence of adverse events in pregnant patients with PH may be lower than previously reported. We conducted a retrospective cohort study in pregnant patients with PH using the National Readmission Database from January 1, 2016, to December 31, 2020. PH was categorized according to the World Health Organization classification. Primary end points include maternal mortality and 30-day nonelective readmission rate. Other adverse short-term maternal (cardiovascular and obstetric) and fetal outcomes were also analyzed. Of 9,922,142 pregnant women, 3,532 (0.04%) had PH, with Group 1 PH noted in 1,833 (51.9%), Group 2 PH in 676 (19.1%), Group 3 PH in 604 (17.1%), Group 4 PH in 23 (0.7%), Group 5 PH in 98 (2.8%), and multifactorial PH in 298 (8.4%). PH patients exhibited higher rates of adverse cardiovascular events (15.7% vs 0.3% without PH, p <0.001) and mortality (0.9% vs 0.01% without PH, p <0.001). Mixed PH and Group 2 PH had the highest prevalence of adverse cardiovascular events in the World Health Organization PH groups. Patients with PH had a significantly higher nonelective 30-day readmission rate (10.4% vs 2.3%) and maternal adverse obstetric events (24.2% vs 9.1%) compared with those without PH (p <0.001) (Figure 1). In conclusion, pregnant women with PH had significantly higher adverse event rates, including in-hospital maternal mortality (85-fold), compared with those without PH.

Heart Failure Patients and Implications of Obesity: A Single-Center Retrospective Study.

Background and objective The prevalence of heart failure (HF) is on the rise; currently, it affects around five million people in the United States (US) and the prevalence is expected to rise from 2.42% in 2012 to 2.97% in 2030. HF is a leading cause of hospitalizations and readmissions, accounting for a major economic burden to the US healthcare system. Obesity is a widely accepted risk factor of HF; however, data regarding its independent association with HF mortality and morbidity is heterogeneous. Globally, more than two-thirds of deaths attributable to high body mass index (BMI) are due to cardiovascular diseases (CVD). This study aimed to investigate the potential role of obesity (BMI >30 Kg/m2) in HF patients in terms of 30-day readmissions, in-hospital mortality, and the use of noninvasive positive pressure ventilation (NIPPV). Methods In this single-center, retrospective study, all adult (age: >18 years) patients who were hospitalized with a primary diagnosis of HF at the Abington Jefferson Hospital from January 2015 to January 2018 were included. Demographic characteristics were collected manually from electronic medical records. Outcomes were 30-day readmission due to HF, all-cause in-hospital mortality, and requirement for NIPPV. Multivariable logistic regression analysis was conducted to investigate the association of obesity with HF outcomes. Results A total of 1,000 patients were initially studied, of these 800 patients were included in the final analysis based on the inclusion criteria. Obese patients showed higher odds for 30-day readmissions and the use of NIPPV compared to non-obese patients. There was no significant difference in in-hospital mortality in obese vs. non-obese patients. Conclusions Based on our findings, BMI >30 Kg/m2 is an independent risk factor for HF readmissions. Additionally, our results highlight the importance of guidelines-directed medical therapy (GDMT) for HF exacerbation, a low threshold for use of NIPPV in obese patients, promotion of lifestyle modifications including weight loss, and early follow-up after discharge to prevent HF readmissions in the obese population.

Dietary nitrate-induced increases in human muscle power: high versus low responders.

Maximal neuromuscular power is an important determinant of athletic performance and also quality of life, independence, and perhaps even mortality in patient populations. We have shown that dietary nitrate (NO3- ), a source of nitric oxide (NO), improves muscle power in some, but not all, subjects. The present investigation was designed to identify factors contributing to this interindividual variability. Healthy men (n = 13) and women (n = 7) 22-79 year of age and weighing 52.1-114.9 kg were studied using a randomized, double-blind, placebo-controlled, crossover design. Subjects were tested 2 h after ingesting beetroot juice (BRJ) either containing or devoid of 12.3 ± 0.8 mmol of NO3- . Plasma NO3- and nitrite (NO2- ) were measured as indicators of NO bioavailability and maximal knee extensor speed (Vmax ), power (Pmax ), and fatigability were determined via isokinetic dynamometry. On average, dietary NO3- increased (P < 0.05) Pmax by 4.4 ± 8.1%. Individual changes, however, ranged from -9.6 to +26.8%. This interindividual variability was not significantly correlated with age, body mass (inverse of NO3- dose per kg), body mass index (surrogate for body composition) or placebo trial Vmax or fatigue index (in vivo indicators of muscle fiber type distribution). In contrast, the relative increase in Pmax was significantly correlated (r = 0.60; P < 0.01) with the relative increase in plasma NO2- concentration. In multivariable analysis female sex also tended (P = 0.08) to be associated with a greater increase in Pmax. We conclude that the magnitude of the dietary NO3- -induced increase in muscle power is dependent upon the magnitude of the resulting increase in plasma NO2- and possibly female sex.

Dietary Nitrate Increases VO2peak and Performance but Does Not Alter Ventilation or Efficiency in Patients With Heart Failure With Reduced Ejection Fraction.

BACKGROUND: Patients with heart failure with reduced ejection fraction (HFrEF) exhibit lower efficiency, dyspnea, and diminished peak oxygen uptake (VO2peak) during exercise. Dietary nitrate (NO3-), a source of nitric oxide (NO), has improved these measures in some studies of other populations. We determined the effects of acute NO3- ingestion on exercise responses in 8 patients with HFrEF using a randomized, double-blind, placebo-controlled, crossover design. METHODS AND RESULTS: Plasma NO3-, nitrite (NO2-), and breath NO were measured at multiple time points and respiratory gas exchange was determined during exercise after ingestion of beetroot juice containing or devoid of 11.2 mmol of NO3-. NO3- intake increased (P < .05-0.001) plasma NO3- and NO2- and breath NO by 1469 ± 245%, 105 ± 34%, and 60 ± 18%, respectively. Efficiency and ventilation during exercise were unchanged. However, NO3- ingestion increased (P < .05) VO2peak by 8 ± 2% (ie, from 21.4 ± 2.1 to 23.0 ± 2.3 mL.min-1.kg-1). Time to fatigue improved (P < .05) by 7 ± 3 % (ie, from 582 ± 84 to 612 ± 81 seconds). CONCLUSIONS: Acute dietary NO3- intake increases VO2peak and performance in patients with HFrEF. These data, in conjunction with our recent data demonstrating that dietary NO3- also improves muscle contractile function, suggest that dietary NO3- supplementation may be a valuable means of enhancing exercise capacity in this population.

Bariatric Surgery-Induced Cardiac and Lipidomic Changes in Obesity-Related Heart Failure with Preserved Ejection Fraction.

OBJECTIVE: To determine the effects of gastric bypass on myocardial lipid deposition and function and the plasma lipidome in women with obesity and heart failure with preserved ejection fraction (HFpEF). METHODS: A primary cohort (N = 12) with HFpEF and obesity underwent echocardiography and magnetic resonance spectroscopy both before and 3 months and 6 months after bariatric surgery. Plasma lipidomic analysis was performed before surgery and 3 months after surgery in the primary cohort and were confirmed in a validation cohort (N = 22). RESULTS: After surgery-induced weight loss, Minnesota Living with Heart Failure questionnaire scores, cardiac mass, and liver fat decreased (P < 0.02, P < 0.001, and P = 0.007, respectively); echo-derived e' increased (P = 0.03), but cardiac fat was unchanged. Although weight loss was associated with decreases in many plasma ceramide and sphingolipid species, plasma lipid and cardiac function changes did not correlate. CONCLUSIONS: Surgery-induced weight loss in women with HFpEF and obesity was associated with improved symptoms, reverse cardiac remodeling, and improved relaxation. Although weight loss was associated with plasma sphingolipidome changes, cardiac function improvement was not associated with lipidomic or myocardial triglyceride changes. The results of this study suggest that gastric bypass ameliorates obesity-related HFpEF and that cardiac fat deposition and lipidomic changes may not be critical to its pathogenesis.

Short-Term Costs and Hospitalization Rates in Patients With Adult Congenital Heart Disease After Pulmonic Valve Replacement.

In the adult congenital heart disease (ACHD) population, pulmonary valve replacement (PVR) is a common intervention, its benefit, however, has been incompletely investigated. This study investigates short- and intermediate-term outcomes after PVR in ACHD. Using State Inpatient Databases from the Healthcare Cost and Utilization Project, we investigated both hospitalization rate and financial burden accrued over the 12-month period after PVR compared with the 12 months before. Among 202 patients who underwent PVR, per patient-year hospitalization rates doubled in the year after PVR compared with the year before (0.16 vs 0.36, p = 0.006). With the exception of postprocedural complications, the most common reasons for hospitalization were unchanged after surgery: 22% of patients were admitted with equal or greater frequency after PVR. These patients experienced higher inpatient costs both at index admission and in the year after PVR (p = 0.004 and p <0.001, respectively). Univariate predictors of increased hospitalizations after PVR were age ≥50 years (p = 0.016), transposition of the great arteries, or conotruncal abnormalities (p <0.001), lipid disorders (p = 0.025), hypertension (p = 0.033), and number of chronic conditions ≥4 (p = 0.004). Multivariate analysis identified transposition of the great arteries or conotruncal abnormalities as an independent risk factor for increased hospitalization and cost post-PVR (p ≤0.001). In conclusion, short-term costs and hospitalization rates increase after PVR in a small group of patients with ACHD.

Epstein-Barr virus-associated nephrotic syndrome.

Acute infection with Epstein-Barr virus (EBV) causes fever, fatigue and pharyngitis. Renal involvement in systemic EBV infections typically manifests as acute tubular necrosis or tubulointerstitial nephritis. Rarely, EBV infection causes nephrotic syndrome due to minimal change disease. A 22-year-old male with infectious mononucleosis (IM) presented with nephrotic syndrome. Renal biopsy showed minimal change disease with diffuse foot process effacement of the podocytes. Treatment with methylprednisone led to rapid and complete clinical remission. Minimal change nephropathy is a very rare manifestation of EBV infection and should be considered in patients with IM and proteinuria.

Myocardial injury after ischemia-reperfusion in mice deficient in Akt2 is associated with increased cardiac macrophage density.

Akt2 protein kinase has been shown to promote cell migration and actin polymerization in several cell types, including macrophages. Because migrating macrophages constitute an important inflammatory response after myocardial ischemia, we determined cardiac macrophage expression after ischemia-reperfusion (I/R) injury and cryo-injury in mice lacking Akt2 (Akt2-KO). At 7 days post-I/R, Akt2-KO cardiac tissues showed an increase in immunohistochemical staining for macrophage markers (Galectin 3 and F4/80) compared with wild-type (WT) mice, indicating macrophage density was increased in the injured Akt2-KO myocardium. This change was time dependent because macrophage density was similar between WT and Akt2-KO myocardium at 3 days post-I/R, but by 7 and 14 days post-I/R, macrophage density was significantly increased in Akt2-KO myocardium. Concomitantly, infarct size was larger and cardiac function was reduced in Akt2-KO mice subjected to I/R. However, when cryo-infarction produced similar infarct sizes in the anterior wall in both WT and Akt2-KO mice, macrophage density remained higher in Akt2-KO mouse myocardium, suggesting Akt2 regulates myocardial macrophage density independent of infarct size. Consistently, bone marrow from Akt2-KO mice enhanced myocardial macrophage density in both C57/B6 WT and Akt2-KO recipient mice. Finally, reciprocal ex-vivo coculturing of macrophages and cardiac myocytes showed that activated Akt2-KO peritoneal macrophages had reduced mobility and adhesion when compared with WT littermate controls. Thus, although Akt-2 KO mice did not affect the initial inflammation response after injury and Akt2 deficiency has been shown to impair cell migration or motility in macrophages, our data suggested a novel mechanism in which increasing retention of Akt2-KO macrophages resulted in increasing cardiac Akt2-KO macrophage density in the myocardial space.