Novel insights into the pathobiology of pulmonary hypertension in heart failure with preserved ejection fraction.

Heart failure (HF) with preserved ejection fraction (HFpEF) is the most common cause of pulmonary hypertension (PH) worldwide and is strongly associated with adverse clinical outcomes. The American Heart Association recently highlighted a call to action regarding the distinct lack of evidence-based treatments for PH due to poorly understood pathophysiology of PH attributable to HFpEF (PH-HFpEF). Prior studies have described cardiophysiological mechanisms to explain the development of isolated postcapillary PH (ipc-PH); however, the consequent increase in pulmonary vascular (PV) resistance (PVR) may lead to the less understood and more fatal combined pre- and postcapillary PH (cpc-PH). Metabolic disease and inflammatory dysregulation have been suggested to predispose PH, yet the molecular mechanisms are unknown. Although PH-HFpEF has been studied to partly share vasoactive neurohormonal mediators with primary pulmonary arterial hypertension (PAH), clinical trials that have targeted these pathways have been unsuccessful. The increased mortality of patients with PH-HFpEF necessitates further study into viable mechanistic targets involved in disease progression. We aim to summarize the current pathophysiological and clinical understanding of PH-HFpEF, highlight the role of known molecular mechanisms in the progression of PV disease, and introduce a novel concept that lipid metabolism may be attenuating and propagating PH-HFpEF.NEW & NOTEWORTHY Our review addresses pulmonary hypertension (PH) attributable to heart failure (HF) with preserved ejection fraction (HFpEF; PH-HFpEF). Current knowledge gaps in PH-HFpEF pathophysiology have led to a lack of therapeutic targets. Thus, we address identified knowledge gaps in a comprehensive review, focusing on current clinical epidemiology, known pathophysiology, and previously studied molecular mechanisms. We also introduce a comprehensive review of polyunsaturated fatty acid (PUFA) lipid inflammatory mediators in PH-HFpEF.

The Association Between Myocardial Bridging and Hypertrophic Cardiomyopathy and Their Implications on Percutaneous Coronary Intervention Outcomes: A Retrospective Study.

Hypertrophic cardiomyopathy (HCM) is a complex cardiac disorder, often associated with adverse outcomes, including sudden cardiac death. Myocardial bridging (MB), where a coronary artery segment traverses intramurally within the myocardium, complicates coronary blood flow dynamics. This retrospective study investigates the relationship between MB and HCM and their impact on percutaneous coronary intervention (PCI) outcomes. Data from the 2019 National Inpatient Sample (NIS), representing 20% of U.S. hospitalizations, was utilized. Patients with both HCM and MB undergoing PCI were identified and analyzed. The study assessed inpatient outcomes, including mortality, length of stay, hospital cost, and post-PCI complications (atrial fibrillation, acute kidney injury, bleeding, coronary dissection). Patients with HCM and MB exhibited distinct demographics. The study did not find significant associations between HCM/MB and inpatient mortality, length of stay, or hospital cost. However, HCM patients had a higher incidence of atrial fibrillation and acute kidney injury post-PCI (aOR 2.33, 95% CI 1.46 to 3.71, p ≤ 0.001). MB was linked to increased occurrences of acute heart failure (aOR 0.62, 95% CI 0.42-0.92, p = 0.02) and post-PCI bleeding (aOR 4.88, 95% CI 1.17-20.2, p = 0.03). This nationwide study reveals unique demographic profiles for HCM and MB patients. Notably, HCM patients face higher risks of post-PCI complications, including atrial fibrillation and acute kidney injury. These findings provide fresh insights into the MB-HCM relationship and its implications for PCI outcomes. They emphasize the need for tailored interventions and improved patient management in cases involving both HCM and MB.

A profile on the CardioMEMS HF system in the management of patients with early stages of heart failure: an update.

INTRODUCTION: Over the past decade, there have been noteworthy advances in the evaluation and treatment of heart failure (HF). Despite an improved understanding of this chronic disease, HF is still one of the leading causes of morbidity and mortality in the United States and worldwide. Decompensation and rehospitalization of HF patients remain an integral problem in disease management, with significant economic implications. Remote monitoring systems have been developed to detect HF decompensation early and address it before hospitalization. The CardioMEMS HF system is a wireless pulmonary artery (PA) monitoring system that detects changes in PA pressure and transmits data to the healthcare provider. As changes in PA pressures occur early during HF decompensation, the CardioMEMS HF system allows providers to institute timely changes in HF medical therapies to alter the course of the decompensation. The use of the CardioMEMS HF system has been shown to reduce HF hospitalization and improve quality of life. AREAS COVERED: This review will focus on the available data supporting the expanded utilization of the CardioMEMS system in patients with HF. EXPERT OPINION: The CardioMEMS HF system is a relatively safe and cost-effective device that reduces the incidence of HF hospitalization and qualifies as intermediate-to-high value medical care.

Endovascular Transcatheter Aortic Valve Replacement Outcomes in Hypertrophic Cardiomyopathy: Insights from the National Inpatient Sample (2014-2018).

BACKGROUND: Outcomes of patients with hypertrophic cardiomyopathy (HCM) following transcatheter aortic valve replacement (TAVR) remain largely unknown. OBJECTIVES: This study sought to assess the clinical characteristics and outcomes of HCM patients following TAVR. METHODS: We queried the National Inpatient Sample from 2014 to 2018 for TAVR hospitalizations with and without HCM, creating a propensity-matched cohort to compare outcomes. RESULTS: 207,880 patients that underwent TAVR during the study period, 810 (0.38%) had coexisting HCM. In the unmatched population, TAVR patients with HCM compared to those without HCM, were more likely to be female, had a higher prevalence of heart failure, obesity, cancer, and history of pacemaker/implantable cardioverter defibrillation, and were more likely to have nonelective and weekend admissions (p for all <0.05). TAVR patients without HCM had higher prevalence of coronary artery disease, prior percutaneous coronary intervention, prior coronary artery bypass grafting, and peripheral arterial disease compared to their counterparts (p for all <0.05). In the propensity-matched cohort, TAVR patients with HCM had significantly higher incidence of in-hospital mortality, acute kidney injury/hemodialysis, bleeding complications, vascular complications, permanent pacemaker requirement, aortic dissection, cardiogenic shock, and mechanical ventilation requirement. CONCLUSION: Endovascular TAVR in HCM patients is associated with an increased incidence of in-hospital mortality and procedural complications.

Early surgery or conservative management for asymptomatic severe aortic stenosis: Meta-analysis of RECOVERY and AVATAR.

The standard practice for management for asymptomatic severe aortic stenosis with a normal left ventricular systolic function is conservative management with a few exceptions. This practice is challenged by two recent randomized controlled trials (RCT). All the prior data is observational. We performed a meta-analysis of these 2 RCTs to determine if early surgical aortic valve replacement in this patient population is beneficial compared with the standard conservative therapy.

Early versus late discharge after transcatheter aortic valve replacement and readmissions for permanent pacemaker implantation.

OBJECTIVE: To examine the rate of readmission for permanent pacemaker (PPM) implantation with early versus late discharge after transcatheter aortic valve replacement (TAVR). BACKGROUND: There is a current trend toward early discharge after TAVR. However, paucity of data exists on the impact of such practice on readmissions for PPM implantation. METHODS: The Nationwide Readmission Database 2016-2018 was queried for all hospitalizations where patients underwent TAVR. Hospitalizations were stratified into early (Days 0 and 1) versus late (≥Day 2) discharge groups. Observations in which PPM was required in the index admission were excluded. Multivariable regression analyses involving patient- and hospital-related variables were utilized. The primary outcome was 90-day readmission for PPM implantation. RESULTS: The final analysis included 68,482 TAVR hospitalizations, 20,261 (29.6%) with early versus 48,221 (70.4%) with late discharge. Early discharge after TAVR increased over the study period (16.2% in 2016 vs. 37.9% in 2018, Ptrend < 0.01). Nevertheless, 90-day readmission for PPM implantation remained stable (1.8% in 2016 vs. 2.0% in 2018, Ptrend = 0.32). The 90-day readmission rate for PPM implantation (2.0% vs. 1.8%; adjusted odds ratio: 1.15; 95% confidence interval: 0.95-1.39; p = 0.15) and median time-to-readmission (5 days [interquartile range, IQR 3-9] vs. 5 days [IQR 3-14], p = 0.92) were similar with early versus late discharge. Similar rates were observed regardless of whether readmission was elective versus not. Early discharge was associated with lower hospitalization cost ($39,990 ± $13,681 vs. $46,750 ± $18,218, p < 0.01) compared with late discharge. CONCLUSION: In patients who did not require PPM during the index TAVR hospitalization, the rate of readmission for PPM implantation was similar with early versus late discharge.

Coronary Artery Aneurysms in ST-Elevation Myocardial Infarction (From a United States Based National Cohort).

This study aimed to study group differences in patients presenting with ST-elevation myocardial infarction (STEMI) based on the presence or absence of associated coronary artery aneurysms (CAA). The cause-and-effect relationship between CAAs and STEMI is largely unknown. The Nationwide Readmission database was used to identify and study group differences of patients with STEMI and with and without CAA from 2014 to 2018. The primary outcome in the 2 groups was mortality. Secondary outcomes in the 2 groups included differences in clinical outcomes, cardiovascular interventions performed, and prevalence of coronary artery dissection. The total number of patients with STEMI included was 1,038,299. In this sample, 1,543 (0.15%) had CAA. Compared with those without CAA, patients with CAAs and STEMI were younger (62.6 vs 65.4), more likely to be male (78 vs 66%), and had a higher prevalence of a history of Kawasaki disease (2.5 vs 0.01%). A difference exists in the prevalence of coronary dissection in patients with STEMI with and without CAA (73% vs 1%). Patients with CAA were more often treated with coronary artery bypass grafting (13.1 vs 5.6%), thrombectomy (16.5 vs 6%), and bare-metal stent implantation (8 vs 4.4). Patients in the CAA STEMI group had lower all-cause mortality (6.3 vs 11.7%). In conclusion, there are important differences in patients with STEMI with and without CAA, which include, but are not limited to, factors such as patient profile, the risk for coronary dissection, treatment, outcomes, and mortality.

The Association of Chronic Kidney Disease With Outcomes Following Percutaneous Left Atrial Appendage Closure.

OBJECTIVES: The aim of this study was to investigate the associations of chronic kidney disease (CKD) and end-stage renal disease (ESRD) with in-hospital and short-term outcomes using a large national database representative of contemporary clinical practice. BACKGROUND: CKD and ESRD are associated with increased risk for stroke and bleeding in patients with atrial fibrillation on oral anticoagulation. Left atrial appendage closure (LAAC) may provide a reasonable alternative for these patients; however, the impact of CKD and ESRD on in-hospital and short-term outcomes following LAAC remain largely unknown. METHODS: The Nationwide Readmissions Database was used to identify LAAC procedures from 2016 to 2017 in patients with no CKD, CKD (stages I-V), and ESRD. Multivariable logistic regression models were used to assess in-hospital and short-term outcomes. The primary outcome was in-hospital mortality. RESULTS: Of 21,274 patients who underwent LAAC during the study period, 3,954 (18.6%) had CKD and 571 (2.7%) had ESRD. ESRD was associated with increased risk for in-hospital mortality compared with no CKD (3.3% vs 0.4%; adjusted odds ratio: 6.48; 95% confidence interval: 3.35-12.50; P < 0.001) and CKD (3.3% vs 0.5%; adjusted odds ratio: 11.43; 95% confidence interval: 4.77-27.39; P < 0.001). CKD was associated with increased risk for in-hospital acute kidney injury or hemodialysis and stroke or transient ischemic attack. ESRD and CKD were associated with increased readmissions extending to 90 days compared with no CKD, and ESRD was associated with increased readmissions compared with CKD. There was no difference with respect to other in-hospital outcomes. CONCLUSIONS: ESRD is associated with higher in-hospital mortality, and CKD is associated with higher rates of stroke or transient ischemic attack in patients undergoing LAAC. Further research is needed to assess the impact of CKD and ESRD on long-term outcomes in these patients.

Bupropion in the treatment of postural orthostatic tachycardia syndrome (POTS): a single-center experience.

Postural orthostatic tachycardia syndrome (POTS) is estimated to impact millions of people each year. However, there is no established gold standard for its treatment. Bupropion is a norepinephrine and a dopamine reuptake inhibitor and has been implicated as a potential treatment for POTS. We performed a non-randomized retrospective chart review on 47 patients with POTS with statistical analysis evaluating for significant findings including reduced orthostasis and improvement of symptoms with the use of bupropion. Bupropion was not associated with a statistically significant improvement in orthostatic vitals but there was an overall reduction in reported syncope. While the use of bupropion does not show a statistically significant impact on orthostatic vitals in patients with POTS, it did show a degree of improvement in syncope and as such might be useful in patients with syncope-predominant POTS.

A Case of Acute Massive Bioprosthetic Mitral Valve Thrombosis Leading to Fulminant Heart Failure.

Bioprosthetic valve thrombosis has been considered to be extremely unlikely, typically freeing patients from the potential complications of long-term anticoagulation. However, there have been several documented cases of bioprosthetic valve thrombosis and there are concerns that its incidence may be underreported. Experience with diagnosis and management of this condition is limited. Here, we present a case of acute massive bioprosthetic mitral thrombosis manifesting as fulminant heart failure.

PD-1-dependent restoration of self-tolerance in the NOD mouse model of diabetes after transient anti-TCRß mAb therapy.

AIMS/HYPOTHESIS: T cells play a major role in the pathogenesis of type 1 diabetes, and there is great interest in developing curative immunotherapies targeting these cells. In this study, a monoclonal antibody (mAb) targeting the T cell receptor ß-chain (TCRß) was investigated for its ability to prevent and reverse disease in mouse models of diabetes. METHODS: RIP-OVA(hi) (C57BL/6-Tg(Ins2-OVA)59Wehi/WehiJ) mice adoptively transferred with ovalbumin-specific T cells (an induced model of diabetes) and NOD mice (a spontaneous model of diabetes) were used to test anti-TCRß mAb therapy as a means of preventing and reversing type 1 diabetes. RESULTS: A single dose of anti-TCRß completely prevented disease in RIP-OVA(hi) mice without inducing the release of inflammatory cytokines. Transient anti-TCRß therapy prevented diabetes in 90% of NOD mice and reversed the disease after its onset in 73% of NOD mice. Long after the remission of type 1 diabetes, the anti-TCRß treated mice were able to reject BALB/c skin allografts with normal kinetics while maintaining normoglycaemia. Treatment did not cause significant reductions in lymphocyte numbers in the spleen or pancreatic lymph nodes, but did result in a decreased percentage of chemokine receptor 9 (CCR9) positive, CD8(+) T cells. Notably, anti-TCRß therapy increased the expression of programmed death 1 (PD-1) on the surface of the T cells; PD-1 expression is important for maintaining anti-TCRß-induced self-tolerance, as type 1 diabetes recurs in mice following a blockade of PD-1 signalling. CONCLUSIONS/INTERPRETATION: Anti-TCRß mAb is a safe and effective immunotherapy that results in reduced numbers of CCR9(+) T cells, an increased expression of PD-1 on T cells and the restoration of self-tolerance in NOD mice.