INTERNATIONAL SOCIETY FOR HEART AND LUNG TRANSPLANTATION GUIDELINES FOR THE EVALUATION AND CARE OF CARDIAC TRANSPLANT CANDIDATES-2024.

The "International Society for Heart and Lung Transplantation Guidelines for the Evaluation and Care of Cardiac Transplant Candidates-2024" updates and replaces the "Listing Criteria for Heart Transplantation: International Society for Heart and Lung Transplantation Guidelines for the Care of Cardiac Transplant Candidates-2006" and the "2016 International Society for Heart Lung Transplantation Listing Criteria for Heart Transplantation: A 10-year Update." The document aims to provide tools to help integrate the numerous variables involved in evaluating patients for transplantation, emphasizing updating the collaborative treatment while waiting for a transplant. There have been significant practice-changing developments in the care of heart transplant recipients since the publication of the International Society for Heart and Lung Transplantation (ISHLT) guidelines in 2006 and the 10-year update in 2016. The changes pertain to 3 aspects of heart transplantation: (1) patient selection criteria, (2) care of selected patient populations, and (3) durable mechanical support. To address these issues, 3 task forces were assembled. Each task force was cochaired by a pediatric heart transplant physician with the specific mandate to highlight issues unique to the pediatric heart transplant population and ensure their adequate representation. This guideline was harmonized with other ISHLT guidelines published through November 2023. The 2024 ISHLT guidelines for the evaluation and care of cardiac transplant candidates provide recommendations based on contemporary scientific evidence and patient management flow diagrams. The American College of Cardiology and American Heart Association modular knowledge chunk format has been implemented, allowing guideline information to be grouped into discrete packages (or modules) of information on a disease-specific topic or management issue. Aiming to improve the quality of care for heart transplant candidates, the recommendations present an evidence-based approach.

Cross-Validation of Risk Scores for Patients Undergoing Transcatheter Edge-to-Edge Repair for Mitral Regurgitation.

Background: Risk scores may identify patients with mitral regurgitation (MR) who are at risk for adverse events, but who may still benefit from transcatheter edge-to-edge repair (TEER). We sought to cross-validate the MitraScore and COAPT risk score to predict adverse events in patients undergoing TEER. Methods: MitraScore validation was carried out in the COAPT population which included 614 patients with FMR who were randomized 1:1 to guideline-directed medical therapy (GDMT) with or without TEER and were followed for 2 years. Validation of the COAPT risk score was carried out in 1007 patients from the MIVNUT registry of TEER-treated patients with both FMR and degenerative MR who were followed for a mean of 2.1 years. The predictive value was assessed using the area under the receiver operating characteristic curve (AUC) plots. The primary outcome was all-cause mortality. Results: The MitraScore had fair to good predictive accuracy for mortality in the overall COAPT trial population (AUC, 0.67); its accuracy was higher in patients treated with TEER (AUC, 0.74) than GDMT alone (AUC, 0.65). The COAPT risk score had fair predictive accuracy for death in the overall MitraScore cohort (AUC, 0.64), which was similar in patients with FMR and degenerative MR (AUC, 0.64 and 0.66, respectively). There was a consistent benefit of treatment with TEER plus GDMT compared with GDMT alone in the COAPT trial population across all MitraScore risk strata. Conclusions: The COAPT risk score and MitraScore are simple tools that are useful for the prediction of 2-year mortality in patients eligible for or undergoing treatment with TEER.

Changes in Left Ventricular Function and Outcomes After Trancatheter Edge-to-Edge Repair for Secondary Mitral Regurgitation.

Background: Transcatheter edge-to-edge repair (TEER) improved outcomes in patients with heart failure (HF) and severe secondary mitral regurgitation (SMR) compared with guideline-directed medical therapy (GDMT) alone regardless of the severity of baseline left ventricular ejection fraction (LVEF). The study aimed to evaluate the effect of early changes in LVEF after TEER and GDMT alone in patients with HF and severe SMR. Methods: Within the COAPT trial, we evaluated outcomes according to changes in LVEF from baseline to 30 days. The primary outcome was all-cause death or HF hospitalization (HFH) between 30 days and 2 years. Results: Among 432 patients with paired echocardiographic data, 182 (42.1%) had increased LVEF (LVEF change 6.0% ± 4.9%) and 250 (57.9%) had a decrease or no change in LVEF (LVEF change -6.6% ± 5.6%) from baseline to 30 days. LVEF at 30 days increased more frequently with GDMT alone compared with TEER plus GDMT (51.4% vs 33.0%; P = .0001). Between 30 days and 2 years, there were no significant differences in death or HFH in the increase LVEF and the decrease LVEF groups (58.8% vs 51.4%; multivariable-adjusted HR, 0.97; 95% CI, 0.87-1.08; P = .59). TEER plus GDMT reduced the 30-day to 2-year rate of death or HFH compared with GDMT alone consistently in patients with increase LVEF and decrease LVEF (Pint = 0.75). Conclusions: Among patients with HF and severe SMR, early improvements in LVEF were more frequent with GDMT alone compared with TEER plus GDMT but were not associated with subsequent outcomes at 2 years. TEER reduced death or HFH during 2-year follow-up irrespective of early LVEF changes.

The utility of urine sodium-guided diuresis during acute decompensated heart failure.

Diuresis to achieve decongestion is a central aim of therapy in patients hospitalized for acute decompensated heart failure (ADHF). While multiple approaches have been tried to achieve adequate decongestion rapidly while minimizing adverse effects, no single diuretic strategy has shown superiority, and there is a paucity of data and guidelines to utilize in making these decisions. Observational cohort studies have shown associations between urine sodium excretion and outcomes after hospitalization for ADHF. Urine chemistries (urine sodium ± urine creatinine) may guide diuretic titration during ADHF, and multiple randomized clinical trials have been designed to compare a strategy of urine chemistry-guided diuresis to usual care. This review will summarize current literature for diuretic monitoring and titration strategies, outline evidence gaps, and describe the recently completed and ongoing clinical trials to address these gaps in patients with ADHF with a particular focus on the utility of urine sodium-guided strategies.

Three Year Outcomes After Bridge to Transplantation ECMO - Pre- and Post- 2018 UNOS Revised Heart Allocation System.

BACKGROUND: Utilization of temporary mechanical circulatory support including veno-arterial extra-corporeal membrane oxygenation (VA-ECMO) as a bridge to heart transplantation (HT) has increased significantly under the revised United Network for Organ Sharing (UNOS) donor heart allocation system since October 2018. The revised heart allocation system aimed to lower waitlist times and mortality for the most critically ill patients requiring bi-ventricular, non-dischargeable, mechanical circulatory support. While previous reports have shown improved 1-year post-HT survival in the current Era, 3-year survival and factors associated with mortality among bridge to transplant (BTT) ECMO patients are not well described. METHODS: We queried the UNOS database for all adult (age ≥ 18 years) heart-only transplants performed between 2010 and 2019. Patients were stratified as either pre- (January 2010 to September 2018; Era 1) or post-allocation change (November 2018 to December 2019; Era 2) cohort based on their HT date. Baseline recipient characteristics and post-transplant outcomes were compared. A Cox regression analysis was performed to explore risk factors for 3-year mortality among BTT-ECMO patients in Era 2. For each Era, 3-year mortality was also compared between BTT ECMO patients and those transplanted without ECMO support. RESULTS: During the study period, 116 patients were BTT ECMO during Era 1 and 154 patients during Era 2. Baseline recipient characteristics were similar in both groups. Median age was 48 (36-58 IQR) years in Era 2 while it was 51 (27-58 IQR) years in Era 1. Majority of BTT-ECMO patients were males in both Era 2 and Era 1 (77.7% vs 71.5%, p = 0.28). Median ECMO run times while listed for HT were significantly shorter (4 days vs 7 days, p < 0.001) in Era 2. Waitlist mortality among BTT ECMO patients was also significantly lower in Era 2 (6.3% vs 19.3%, p < 0.001). Post-HT survival at 6 months (94.2% vs 75.9%, p < 0.001), 1 year (90.3% vs 74.2%, p < 0.001), and 3 years (87% vs 66.4%, p < 0.001) was significantly improved in Era 2 as compared to Era 1. Graft failure at 1 year (10.3% vs 25.8%, p = 0.0006) and 3 years (13.6% vs 33.6%, p=0.0001) was also significantly lower in Era 2 compared to Era 1. Three-year survival among BTT ECMO patients in Era 2 was similar to that of patients transplanted in Era 2 without ECMO support (87% vs 85.7%, p=0.75). In multi-variable analysis of BTT-ECMO patients in Era 2, every 1 kg/m2 increase in body mass index (BMI) was associated with higher mortality at 3 years (HR 1.09, 95% CI 1.02-1.15, p = 0.006). Similarly, both post-HT stroke (HR 5.58, 95% CI 2.57-12.14, p < 0.001) and post-HT renal failure requiring hemodialysis (HR 4.36, 95% CI 2.43-7.82, p < 0.001) were also associated with 3-year mortality. CONCLUSION: Three years post-HT survival in patients bridged with ECMO has significantly improved under the revised donor heart allocation system compared to prior system. BTT ECMO recipients under the revised system have significantly shorter ECMO waitlist run times, lower waitlist mortality and 3-year survival similar to those not bridged with ECMO. Overall, the revised allocation system has allowed more rapid transplantation of the sickest patients without a higher post-HT mortality.

Tricuspid Regurgitation in Patients With Heart Failure and Preserved Ejection Fraction: JACC State-of-the-Art Review.

Heart failure with preserved ejection fraction (HFpEF) is associated with high morbidity and mortality. Important risk factors for the development of HFpEF are similar to risk factors for the progression of tricuspid regurgitation (TR), and both conditions frequently coexist and thus is a distinct phenotype or a marker for advanced HF. Many patients with severe, symptomatic atrial secondary TR have been enrolled in current transcatheter device trials, and may represent patients at an advanced stage of HFpEF. Management of HFpEF thus may affect the pathophysiology of TR, and the physiologic changes that occur following transcatheter treatment of TR, may also impact symptoms and outcomes in patients with HFpEF. This review discusses these issues and suggests possible management strategies for these patients.

Heart Failure Drug Development Over the Eras: From the Heart Failure Collaboratory.

Over the past decade, the field of heart failure (HF) has witnessed remarkable progress in drug development, resulting in the approval of numerous groundbreaking drugs by the U.S. Food and Drug Administration. To address some of these challenges, the U.S. Food and Drug Administration has issued guidance documents that have been critical in contemporary HF drug development; however, there are still many challenges in need of investigation. This article leverages efforts of the Heart Failure Collaboratory and the scientific community to discuss the critical need for innovative trial designs, important concepts in clinical trials in the modern era, and the utilization of big data to accelerate HF drug development. At this inflection point in HF drug development, it is imperative that, as a global scientific community, we foster increased collaboration among researchers, clinicians, patients, and regulatory bodies. Only through such unified efforts can we navigate the complexities of HF, accelerate the development process, and ultimately deliver effective therapies that transform patient outcomes.

Leadless Ultrasound-Based Cardiac Resynchronization System in Heart Failure.

Importance: Approximately 40% of patients with heart failure (HF) who are eligible for cardiac resynchronization therapy (CRT) either fail to respond or are untreatable due to anatomical constraints. Objective: To assess the safety and efficacy of a novel, leadless, left ventricular (LV) endocardial pacing system for patients at high risk for a CRT upgrade or whose coronary sinus (CS) lead placement/pacing with a conventional CRT system failed. Design, Setting, and Participants: The SOLVE-CRT study was a prospective multicenter trial, enrolling January 2018 through September 2022, with follow-up in March 2023. Data were analyzed from DATE MONTH, YEAR, through DATE MONTH, YEAR. The trial combined data from an initial randomized, double-blind study (n = 108) and a subsequent single-arm part (n = 75). It took place at 36 centers across Australia, Europe, and the US. Participants were nonresponders, previously untreatable (PU), or high-risk upgrades (HRU). All participants contributed to the safety analysis. The primary efficacy analysis (n = 100) included 75 PU-HRU patients from the single-arm part and 25 PU-HRU patients from the randomized treatment arm. Interventions: Patients were implanted with the WiSE CRT System (EBR Systems) consisting of a leadless LV endocardial pacing electrode stimulated with ultrasound energy delivered by a subcutaneously implanted transmitter and battery. Main Outcomes and Measures: The primary safety end point was freedom from type I complications. The primary efficacy end point was a reduction in mean LV end systolic volume (LVESV). Results: The study included 183 participants; mean age was 68.1 (SD, 10.3) years and 141 were male (77%). The trial was terminated at an interim analysis for meeting prespecified stopping criteria. In the safety population, patients were either New York Heart Association Class II (34.6%) or III (65.4%). The primary efficacy end point was met with a 16.4% (95% CI, -21.0% to -11.7%) reduction in mean LVESV (P = .003). The primary safety end point was met with an 80.9% rate of freedom from type I complications (P < .001), which included 12 study device system events (6.6%), 5 vascular events (2.7%), 3 strokes (1.6%), and 7 cardiac perforations which mostly occurred early in the study (3.8%). Conclusions and Relevance: The SOLVE-CRT study has demonstrated that leadless LV endocardial pacing with the WiSE CRT system is associated with a reduction in LVESV in patients with HF. This novel system may represent an alternative to conventional CRT implants in some HF patient populations. Trial Registration: ClinicalTrials.gov Identifier: NCT0292203.

American Heart Association Cardiogenic Shock Registry: Design and Implementation.

BACKGROUND: Cardiogenic shock is a morbid complication of heart disease that claims the lives of more than 1 in 3 patients presenting with this syndrome. Supporting a unique collaboration across clinical specialties, federal regulators, payors, and industry, the American Heart Association volunteers and staff have launched a quality improvement registry to better understand the clinical manifestations of shock phenotypes, and to benchmark the management patterns, and outcomes of patients presenting with cardiogenic shock to hospitals across the United States. METHODS: Participating hospitals will enroll consecutive hospitalized patients with cardiogenic shock, regardless of etiology or severity. Data are collected through individual reviews of medical records of sequential adult patients with cardiogenic shock. The electronic case record form was collaboratively designed with a core minimum data structure and aligned with Shock Academic Research Consortium definitions. This registry will allow participating health systems to evaluate patient-level data including diagnostic approaches, therapeutics, use of advanced monitoring and circulatory support, processes of care, complications, and in-hospital survival. Participating sites can leverage these data for onsite monitoring of outcomes and benchmarking versus other institutions. The registry was concomitantly designed to provide a high-quality longitudinal research infrastructure for pragmatic randomized trials as well as translational, clinical, and implementation research. An aggregate deidentified data set will be made available to the research community on the American Heart Association's Precision Medicine Platform. On March 31, 2022, the American Heart Association Cardiogenic Shock Registry received its first clinical records. At the time of this submission, 100 centers are participating. CONCLUSIONS: The American Heart Association Cardiogenic Shock Registry will serve as a resource using consistent data structure and definitions for the medical and research community to accelerate scientific advancement through shared learning and research resulting in improved quality of care and outcomes of shock patients.

Left Atrial Improvement in Patients With Secondary Mitral Regurgitation and Heart Failure: The COAPT Trial.

BACKGROUND: Functional mitral regurgitation induces adverse effects on the left ventricle and the left atrium. Left atrial (LA) dilatation and reduced LA strain are associated with poor outcomes in heart failure (HF). Transcatheter edge-to-edge repair (TEER) of the mitral valve reduces heart failure hospitalization (HFH) and all-cause death in selected HF patients. OBJECTIVES: The aim of this study was to evaluate the impact of LA strain improvement 6 months after TEER on the outcomes of patients enrolled in the COAPT (Cardiovascular Outcomes Assessment of the MitraClip Percutaneous Therapy for Heart Failure Patients With Functional Mitral Regurgitation) trial. METHODS: The difference in LA strain between baseline and the 6-month follow-up was calculated. Patients with at least a 15% improvement in LA strain were labeled as "LA strain improvers." All-cause death and HFH were assessed between the 6 and 24-month follow-up. RESULTS: Among 347 patients (mean age 71 ± 12 years, 63% male), 106 (30.5%) showed improvement of LA strain at the 6-month follow-up (64 [60.4%] from the TEER + guideline-directed medical therapy [GDMT] group and 42 [39.6%] from the GDMT alone group). An improvement in LA strain was significantly associated with a reduction in the composite of death or HFH between the 6-month and 24-month follow-up, with a similar risk reduction in both treatment arms (Pinteraction = 0.27). In multivariable analyses, LA strain improvement remained independently associated with a lower risk of the primary composite endpoint both as a continuous variable (adjusted HR: 0.94 [95% CI: 0.89-1.00]; P = 0.03) and as a dichotomous variable (adjusted HR: 0.49 [95% CI: 0.27-0.89]; P = 0.02). The best outcomes were observed in patients treated with TEER in whom LA strain improved. CONCLUSIONS: In symptomatic HF patients with severe mitral regurgitation, improved LA strain at the 6-month follow-up is associated with subsequently lower rates of the composite endpoint of all-cause mortality or HFH, both after TEER and GDMT alone. (Cardiovascular Outcomes Assessment of the MitraClip Percutaneous Therapy for Heart Failure Patients With Functional Mitral Regurgitation [COAPT]; NCT01626079).

In vivo fluid dynamics of the Ventura interatrial shunt device in patients with heart failure.

AIMS: Interatrial shunts are under evaluation as a treatment for heart failure (HF); however, their in vivo flow performance has not been quantitatively studied. We aimed to investigate the fluid dynamics properties of the 0.51 cm orifice diameter Ventura shunt and assess its lumen integrity with serial transesophageal echocardiography (TEE). METHODS AND RESULTS: Computational fluid dynamics (CFD) and bench flow tests were used to establish the flow-pressure relationship of the shunt. Open-label patients from the RELIEVE-HF trial underwent TEE at shunt implant and at 6 and 12 month follow-up. Shunt effective diameter (Deff) was derived from the vena contracta, and flow was determined by the continuity equation. CFD and bench studies independently validated that the shunt's discharge coefficient was 0.88 to 0.89. The device was successfully implanted in all 97 enrolled patients; mean age was 70 ± 11 years, 97% were NYHA class III, and 51% had LVEF ≤40%. Patency was confirmed in all instances, except for one stenotic shunt at 6 months. Deff remained unchanged from baseline at 12 months (0.47 ± 0.01 cm, P = 0.376), as did the trans-shunt mean pressure gradient (5.1 ± 3.9 mmHg, P = 0.316) and flow (1137 ± 463 mL/min, P = 0.384). TEE measured flow versus pressure closely correlated (R2 ≥ 0.98) with a fluid dynamics model. At 12 months, the pulmonary/systemic flow Qp/Qs ratio was 1.22 ± 0.12. CONCLUSIONS: When implanted in patients with advanced HF, this small interatrial shunt demonstrated predictable and durable patency and performance.

Repeat Mitral Valve Interventions After Transcatheter Edge-to-Edge Repair: The COAPT Trial.

The frequency and effectiveness of repeat mitral valve interventions (RMVI) after transcatheter edge-to-edge repair (TEER) for secondary mitral regurgitation (MR) are unknown. We aimed to examine the rate of and outcomes after RMVI after TEER in the Cardiovascular Outcomes Assessment of the MitraClip Percutaneous Therapy for Heart Failure Patients with Functional Mitral Regurgitation (COAPT) trial. Only 3.9% of COAPT trial patients required a repeat mitral valve intervention during 4-year follow-up which was successful in 90% of cases but was associated with an increased rate of heart failure (HF) hospitalizations (HFH). The COAPT trial randomized HF patients with severe secondary MR to TEER with the MitraClip device plus guideline-directed medical therapy (GDMT) versus GDMT alone. We evaluated the characteristics and outcomes of patients who had an RMVI during 4-year follow-up. A MitraClip implant was attempted in 293 patients randomized to TEER+GDMT, 10 of whom underwent an RMVI procedure (9 repeat TEER and 1 surgical mitral valve replacement) after 4 years of follow-up (cumulative incidence 3.90%, 95% confidence interval [CI] 2.08 to 7.08; median 182 days after the initial procedure). Patients with RMVI had larger mitral annular diameters, fewer clips implanted, and were more likely to have ≥3+MR at discharge compared with those without RMVI. Reasons for RMVI included failed index procedure because of difficult transseptal puncture (n = 2) or tamponade (n = 1); residual or recurrent severe MR after an initially successful procedure (n = 5); partial clip detachment (n = 1); and site-assessed mitral stenosis (n = 1). RMVI was successful in 8/10 (80%) patients. Patients who underwent RMVI had higher 4-year rates of HFH but similar mortality compared with those without RMVI. The annualized incidence rates of all HFH in patients who underwent RMVI were 234 events per 100 person-years (95% CI 139 to 395) pre-RMVI and 46 per 100 person-years (95% CI 25 to 86) post-RMVI as compared with 32 events per 100 patient-years (95% CI 28 to 36) in patients without RMVI. The rate ratio of HFH was reduced after RMVI in patients who underwent RMVI (0.20, 95% CI 0.09 to 0.45). In conclusion, the cumulative incidence of RMVI after 4 years was 3.9% in patients who underwent TEER for severe secondary MR in the COAPT trial. Patients who underwent RMVI were at increased risk of HFH which was reduced after the RMVI procedure. Clinical Trial Registration: Clinical Trial Name: Cardiovascular Outcomes Assessment of the MitraClip Percutaneous Therapy for Heart Failure Patients With Functional Mitral Regurgitation (The COAPT Trial) (COAPT) ClinicalTrial.gov Identifier: NCT01626079 URL:https://clinicaltrials.gov/ct2/show/NCT01626079.

Bias in team decision-making for advanced heart failure therapies: model application.

Bias in advanced heart failure therapy allocation results in inequitable outcomes for minoritized populations. The purpose of this study was to examine how bias is introduced during group decision-making with an interprofessional team using Breathett's Model of Heart Failure Decision-Making. This was a secondary qualitative descriptive analysis from a study focused on bias in advanced heart failure therapy allocation. Team meetings were recorded and transcribed from four heart failure centers. Breathett's Model was applied both deductively and inductively to transcripts (n = 12). Bias was identified during discussions about patient characteristics, clinical fragility, and prior clinical decision-making. Some patients were labeled as "good citizens" or as adherent/non-adherent while others benefited from strong advocacy from interprofessional team members. Social determinants of health also impacted therapy allocation. Interprofessional collaboration with advanced heart failure therapy allocation may be enhanced with the inclusion of patient advocates and limit of clinical decision-making using subjective data.

Efficient measurement of multiple ventricular assist device patient-reported outcomes: Creation of a 20-item profile from the MCS A-QOL study.

BACKGROUND: Patient-reported outcome (PRO) measures of distinct concepts are often put together into patient profile assessments. When brief, profile assessments can decrease respondent burden and increase measure completion rates. In this report, we describe the creation of 5 self-reported 4-item short forms and the Mechanical Circulatory Support: Measures of Adjustment and Quality of Life (MCS A-QOL) 20-item profile to assess PROs specific to adjustment and health-related quality of life (HRQOL) among patients who undergo left ventricular assist device (LVAD) implantation. METHODS: Using a cross-sectional sample of patients (n = 620) who underwent LVAD implantation at 12 U.S. sites or participated in the MyLVAD.com support group, we created 5 4-item short forms: Satisfaction with Treatment, ventricular assist device (VAD) Team Communication, Being Bothered by VAD Self-care and Limitations, Self-efficacy Regarding VAD self-care, and Stigma, which we combined into a 20-item profile. Analyses included intercorrelations among measures, Cronbach's alpha (i.e., internal consistency reliability)/score-level-specific reliability, and construct validity. RESULTS: The 620 patients were mean age = 57 years, 78% male, 70% White, and 56% on destination therapy LVADs. Intercorrelations among the 5 4-item measures were low to moderate (≤0.50), indicating they are associated yet largely distinct, and correlations with calibrated measures and 6-item short forms were ≥0.76, indicating their ability to reflect full-item bank scores. Internal consistency reliability for the 5 4-item short forms ranged from acceptable (≥0.70) to good (≥0.80). Construct validity was demonstrated for these measures. CONCLUSIONS: Our 5 4-item short forms are reliable and valid and may be used individually or together as a 20-item profile to assess adjustment and HRQOL in patients who undergo LVAD implantation.

Efficacy and Safety of Dapagliflozin in Patients With Acute Heart Failure.

BACKGROUND: The primary goals during acute heart failure (AHF) hospitalization are decongestion and guideline-directed medical therapy (GDMT) optimization. Unlike diuretics or other GDMT, early dapagliflozin initiation could achieve both AHF goals. OBJECTIVES: The authors aimed to assess the diuretic efficacy and safety of early dapagliflozin initiation in AHF. METHODS: In a multicenter, open-label study, 240 patients were randomized within 24 hours of hospital presentation for hypervolemic AHF to dapagliflozin 10 mg once daily or structured usual care with protocolized diuretic titration until day 5 or hospital discharge. The primary outcome, diuretic efficiency expressed as cumulative weight change per cumulative loop diuretic dose, was compared across treatment assignment using a proportional odds model adjusted for baseline weight. Secondary and safety outcomes were adjudicated by a blinded committee. RESULTS: For diuretic efficiency, there was no difference between dapagliflozin and usual care (OR: 0.65; 95% CI: 0.41-1.02; P = 0.06). Dapagliflozin was associated with reduced loop diuretic doses (560 mg [Q1-Q3: 260-1,150 mg] vs 800 mg [Q1-Q3: 380-1,715 mg]; P = 0.006) and fewer intravenous diuretic up-titrations (P ≤ 0.05) to achieve equivalent weight loss as usual care. Early dapagliflozin initiation did not increase diabetic, renal, or cardiovascular safety events. Dapagliflozin was associated with improved median 24-hour natriuresis (P = 0.03) and urine output (P = 0.005), expediting hospital discharge over the study period. CONCLUSIONS: Early dapagliflozin during AHF hospitalization is safe and fulfills a component of GDMT optimization. Dapagliflozin was not associated with a statistically significant reduction in weight-based diuretic efficiency but was associated with evidence for enhanced diuresis among patients with AHF. (Efficacy and Safety of Dapagliflozin in Acute Heart Failure [DICTATE-AHF]; NCT04298229).

New Approaches to Assessment and Management of Tricuspid Regurgitation Before Intervention.

Severe tricuspid regurgitation (TR) is a progressive condition associated with substantial morbidity, poor quality of life, and increased mortality. Patients with TR commonly have coexisting conditions including congestive heart failure, pulmonary hypertension, chronic lung disease, atrial fibrillation, and cardiovascular implantable electronic devices, which can increase the complexity of medical and surgical TR management. As such, the optimal timing of referral for isolated tricuspid valve (TV) intervention is undefined, and TV surgery has been associated with elevated risk of morbidity and mortality. More recently, an unprecedented growth in TR treatment options, namely the development of a wide range of transcatheter TV interventions (TTVI) is stimulating increased interest and referral for TV intervention across the entire medical community. However, there are no stepwise algorithms for the optimal management of symptomatic severe TR before TTVI. This article reviews the contemporary assessment and management of TR with addition of a medical framework to optimize TR before referral for TTVI.

Genitourinary Tract Infections in Patients Taking SGLT2 Inhibitors: JACC Review Topic of the Week.

Sodium-glucose cotransporter-2 inhibitors (SGLT2is) have been shown to reduce adverse cardiovascular events in patients with type 2 diabetes mellitus, all-cause mortality, and heart failure hospitalization in patients with heart failure, as well as adverse renal outcomes. However, concerns regarding the heightened risk of genitourinary (GU) infections, particularly urinary tract infections, remain a significant barrier to their wider adoption. Addressing these misconceptions using existing evidence is needed to ensure proper risk-benefit assessment and optimal utilization of this efficacious therapy. This review aims to provide a balanced perspective on the evidence-based cardiovascular and renal benefits of SGLT2is and the associated risk of GU infections. We also summarize and propose clinical practice considerations for SGLT2i-associated GU infections focusing on patients with cardiovascular disease.

Interatrial shunt therapy in advanced heart failure: Outcomes from the open-label cohort of the RELIEVE-HF trial.

AIMS: Heart failure (HF) outcomes remain poor despite optimal guideline-directed medical therapy (GDMT). We assessed safety, effectiveness, and transthoracic echocardiographic (TTE) outcomes during the 12 months after Ventura shunt implantation in the RELIEVE-HF open-label roll-in cohort. METHODS AND RESULTS: Eligibility required symptomatic HF despite optimal GDMT with ≥1 HF hospitalization in the prior year or elevated natriuretic peptides. The safety endpoint was device-related major adverse cardiovascular or neurological events at 30 days, compared to a prespecified performance goal. Effectiveness evaluations included the Kansas City Cardiomyopathy Questionnaire (KCCQ) at baseline, 1, 3, 6, and 12 months and TTE at baseline and 12 months. Overall, 97 patients were enrolled and implanted at 64 sites. Average age was 70 ± 11 years, 97% were in New York Heart Association class III, and half had left ventricular ejection fraction (LVEF) ≤40%. The safety endpoint was achieved (event rate 0%, p < 0.001). KCCQ overall summary score was improved by 12-16 points at all follow-up timepoints (all p < 0.004), with similar outcomes in patients with reduced and preserved LVEF. At 12 months, left ventricular end-systolic and end-diastolic volumes were reduced (p = 0.020 and p = 0.038, respectively), LVEF improved (p = 0.009), right ventricular end-systolic and end-diastolic areas were reduced (p = 0.001 and p = 0.030, respectively), and right ventricular fractional area change (p < 0.001) and tricuspid annular plane systolic excursion (p < 0.001) improved. CONCLUSION: Interatrial shunting with the Ventura device was safe and resulted in favourable clinical effects in patients with HF, regardless of LVEF. Improvements of left and right ventricular structure and function were consistent with reverse myocardial remodelling. These results would support the potential of this shunt device as a treatment for HF.