Sustained Pericarditis Recurrence Risk Reduction With Long-Term Rilonacept.

Background: Rilonacept, a once-weekly interleukin-1 alpha and beta cytokine trap, reduced pericarditis recurrence in the phase 3 study, RHAPSODY (Rilonacept Inhibition of Interleukin-1 Alpha and Beta for Recurrent Pericarditis: A Pivotal Symptomatology and Outcomes Study). The RHAPSODY long-term extension further explored recurrent pericarditis natural history and treatment duration decision-making during 24 additional months of open-label rilonacept treatment.

Methods And Results: Seventy-four patients commenced the long-term extension, with a median (maximum) total rilonacept duration of 22 (35) months.

Effect of Personalized Accelerated Pacing on Quality of Life, Physical Activity, and Atrial Fibrillation in Patients With Preclinical and Overt Heart Failure With Preserved Ejection Fraction: The myPACE Randomized Clinical Trial.

Importance: Patients with heart failure with preserved ejection fraction (HFpEF) with a pacemaker may benefit from a higher, more physiologic backup heart rate than the nominal 60 beats per minute (bpm) setting.

Objective: To assess the effects of a moderately accelerated personalized backup heart rate compared with 60 bpm (usual care) in patients with preexisting pacemaker systems that limit pacemaker-mediated dyssynchrony.

Design, Setting, And Participants: This blinded randomized clinical trial enrolled patients with stage B and C HFpEF from the University of Vermont Medical Center pacemaker clinic between June 2019 and November 2020.

Interleukin-1 Trap Rilonacept Improved Health-Related Quality of Life and Sleep in Patients With Recurrent Pericarditis: Results From the Phase 3 Clinical Trial RHAPSODY.

Background Recurrent pericarditis is characterized by painful flares and inflammation, which negatively impact health-related quality of life. RHAPSODY (rilonacept inhibition of interleukin-1 alpha and beta for recurrent pericarditis: a pivotal symptomatology and outcomes study) evaluated the efficacy and safety of rilonacept (IL-1α and -β cytokine trap) in recurrent pericarditis. A secondary analysis of these data evaluated the patient-reported outcome questionnaire score change during the trial.

Recurrent Pericarditis: a Stubborn Opponent Meets New Treatments in 2022.

Purpose Of Review: Our goal in writing this review was to provide a comprehensive appraisal of current therapies for idiopathic recurrent pericarditis with a particular focus on the newest therapeutic agents. We sought to understand the role of the inflammasome in the pathophysiology of pericarditis and how it informs the use of interleukin-1 (IL-1)-directed therapies.

Recent Findings: The latest research on this topic has focused on the critical role of the NLRP3 (NACHT, leucine-rich repeat, and pyrin domain-containing protein) inflammasome.

Acute Kidney Injury and Renin-Angiotensin System Inhibition Following Transcatheter Aortic Valve Replacement.

Objective: To identify renin-angiotensin system (RAS) inhibition utilization and discontinuation after transcatheter aortic valve replacement (TAVR) and identify predictors of use and discontinuation.

Background: RAS inhibition after TAVR has been associated with lower cardiac mortality and heart failure readmissions.

Methods: We analyzed 735 consecutive TAVR patients (2014-2019) who survived to hospital discharge at a high-volume TAVR center to determine the utilization and discontinuation of RAS inhibition after TAVR and identify predictors of use and discontinuation.

Health-related quality of life in patients with recurrent pericarditis: results from a phase 2 study of rilonacept.

Background: Impact of recurrent pericarditis (RP) on patient health-related quality of life (HRQoL) was evaluated through qualitative patient interviews and as an exploratory endpoint in a Phase 2 trial evaluating the efficacy and safety of rilonacept (IL-1α/IL-1β cytokine trap) to treat RP.

Methods: Qualitative interviews were conducted with ten adults with RP to understand symptoms and HRQoL impacts, and the 10-item Patient-Reported Outcomes Measurement Information System Global Health (PROMIS GH) v1.2 was evaluated to determine questionnaire coverage of patient experience.

Heart Rate-Induced Myocardial Ca Retention and Left Ventricular Volume Loss in Patients With Heart Failure With Preserved Ejection Fraction.

Background Increases in heart rate are thought to result in incomplete left ventricular (LV) relaxation and elevated filling pressures in patients with heart failure with preserved ejection fraction (HFpEF). Experimental studies in isolated human myocardium have suggested that incomplete relaxation is a result of cellular Ca overload caused by increased myocardial Na levels. We tested these heart rate paradigms in patients with HFpEF and referent controls without hypertension.

Enhancing diastolic function by strain-dependent detachment of cardiac myosin crossbridges.

The force response of cardiac muscle undergoing a quick stretch is conventionally interpreted to represent stretching of attached myosin crossbridges (phase 1) and detachment of these stretched crossbridges at an exponential rate (phase 2), followed by crossbridges reattaching in increased numbers due to an enhanced activation of the thin filament (phases 3 and 4). We propose that, at least in mammalian cardiac muscle, phase 2 instead represents an enhanced detachment rate of myosin crossbridges due to stretch, phase 3 represents the reattachment of those same crossbridges, and phase 4 is a passive-like viscoelastic response with power-law relaxation. To test this idea, we developed a two-state model of crossbridge attachment and detachment.

Subclinical cardiac stiffness is associated with arterial stiffness in healthy young nulligravid women: Potential links to preeclampsia.

Objectives: Preeclampsia is an independent risk factor for subsequent cardiovascular disease and diastolic dysfunction and has been linked to arterial stiffness. We hypothesized that arterial stiffness would be associated with echocardiographic markers of diastolic dysfunction in healthy nulligravid women.

Study Design: 31 healthy nulligravid women underwent assessment of peripheral arterial stiffness via aorto-femoral pulse wave velocity, popliteal distensibility and β stiffness measures as well as hemodynamic response to volume challenge.

Characterization of the Obese Phenotype of Heart Failure With Preserved Ejection Fraction: A RELAX Trial Ancillary Study.

Objective: To characterize the obese heart failure with preserved ejection fraction (HFpEF) phenotype in a multicenter cohort.

Patients And Methods: This was a secondary analysis of the randomized clinical trial RELAX (Phosphodiesterase-5 Inhibition to Improve Clinical Status and Exercise Capacity in Heart Failure with Preserved Ejection Fraction) performed between October 1, 2008, and February 1, 2012. Patients with HFpEF were classified by body mass index (BMI) as obese (BMI≥35 kg/m) and nonobese (BMI<30 kg/m) for comparison.

Effect of Inorganic Nitrite vs Placebo on Exercise Capacity Among Patients With Heart Failure With Preserved Ejection Fraction: The INDIE-HFpEF Randomized Clinical Trial.

Importance: There are few effective treatments for heart failure with preserved ejection fraction (HFpEF). Short-term administration of inorganic nitrite or nitrate preparations has been shown to enhance nitric oxide signaling, which may improve aerobic capacity in HFpEF.

Objective: To determine the effect of 4 weeks' administration of inhaled, nebulized inorganic nitrite on exercise capacity in HFpEF.

Pro-Inflammatory Biomarkers in Stable Versus Acutely Decompensated Heart Failure With Preserved Ejection Fraction.

Background: Underlying inflammation has been increasingly recognized in heart failure with a preserved ejection fraction (HFpEF). In this study we tested the hypothesis that pro-inflammatory biomarkers are elevated in patients with acutely decompensated HFpEF (AD-HFpEF) compared with patients with stable HFpEF (S-HFpEF).

Methods And Results: Using a post hoc analysis the serum biomarkers tumor necrosis factor-alpha, high-sensitivity C-reactive protein interleukin 6 and pentraxin 3 (PTX3) and clinical, demographic, echocardiographic-Doppler and clinical outcomes data were analyzed in HFpEF patients enrolled in NHLBI Heart Failure Research Network clinical trials which enrolled patients with either AD-HFpEF or S-HFpEF.

Mechanical Intervention for Aortic Valve Stenosis in Patients With Heart Failure and Reduced Ejection Fraction.

The risk and benefit of mechanical interventions in valvular heart disease have been primarily described among patients with normal ejection fraction. The advent of nonsurgical mechanical interventions for aortic stenosis (transcatheter aortic valve replacement) may alter the risk-benefit ratio for patients who would otherwise be at increased risk for valve surgery. This review describes the epidemiology and pathophysiology of aortic stenosis with heart failure and reduced ejection fraction and summarizes the current registry and clinical trial data applicable to this frequently encountered high-risk group.

Abundance, localization, and functional correlates of the advanced glycation end-product carboxymethyl lysine in human myocardium.

Advanced glycation end-products (AGEs) play a role in the pathophysiology of diabetes mellitus (DM) and possibly hypertension (HTN). In DM, AGEs accumulate in myocardium. Little is known about AGEs in myocardium.

Pericardial Effusion.

The normal pericardial sac contains up to 50 mL of fluid, which consists of a plasma ultrafiltrate. Anything greater constitutes a pathologic effusion. The curvilinear pressure-volume relationship of the pericardial sac dictates hemodynamic consequences of a pericardial effusion and is responsible for rapidly accumulating fluid that causes cardiac tamponade.

Relaxation and the Role of Calcium in Isolated Contracting Myocardium From Patients With Hypertensive Heart Disease and Heart Failure With Preserved Ejection Fraction.

Background: Relaxation characteristics and Ca homeostasis have not been studied in isolated myocardium from patients with hypertensive heart disease (HHD) and heart failure with preserved ejection fraction (HFpEF). Prolonged myocardial relaxation is believed to play an important role in the pathophysiology of these conditions. In this study, we evaluated relaxation parameters, myocardial calcium (Ca), and sodium (Na) handling, as well as ion transporter expression and tested the effect of Na-influx inhibitors on relaxation in isolated myocardium from patients with HHD and HFpEF.

Heart rate-induced modifications of concentric left ventricular hypertrophy: exploration of a novel therapeutic concept.

Lowering the heart rate is considered to be beneficial in heart failure (HF) with reduced ejection fraction (HFrEF). In a dilated left ventricle (LV), pharmacological heart rate lowering is associated with a reduction in LV chamber size. In patients with HFrEF, this structural change is associated with better survival.