Kidney and Cardiovascular Effectiveness of SGLT2 Inhibitors vs GLP-1 Receptor Agonists in Type 2 Diabetes.

BACKGROUND: Emerging data suggest that glucagon-like peptide-1 receptor agonists (GLP-1 RAs) improve kidney outcomes for people with type 2 diabetes (T2D). Direct comparisons of the kidney and cardiovascular effectiveness of GLP-1 RA with sodium-glucose cotransporter 2 inhibitors (SGLT2i), a first-line therapy for this population, are needed. OBJECTIVES: The authors compared kidney and cardiovascular outcomes for new users of SGLT2i and GLP-1 RAs with T2D. METHODS: Using propensity score overlap weighting, we analyzed electronic health record data from 20 U.S. health systems contributing to PCORnet between 2015 and 2020. The primary kidney outcome was a composite of sustained 40% estimated glomerular filtration rate (eGFR) decline, incident end-stage kidney disease, or all-cause mortality over 2 years or until censoring. In addition, we examined cardiovascular and safety outcomes. RESULTS: The weighted study cohort included 35,004 SGLT2i and 47,268 GLP-1 RA initiators. Over a median of 1.2 years, the primary outcome did not differ between treatments (HR: 0.91; 95% CI: 0.81-1.02), although SGLT2i were associated with a lower risk of 40% eGFR decline (HR: 0.77; 95% CI: 0.65-0.91). Risks of mortality (HR: 1.08; 95% CI: 0.92-1.27), a composite of stroke, myocardial infarction, or death (HR: 1.03; 95% CI: 0.93-1.14), and heart failure hospitalization (HR: 0.95; 95% CI: 0.80-1.13) did not differ. Genital mycotic infections were more common for SGLT2i initiators, but other safety outcomes did not differ. The results were similar regardless of chronic kidney disease status. CONCLUSIONS: SGLT2i and GLP-1 RAs led to similar kidney and cardiovascular outcomes in people with T2D, though SGLT2i initiation was associated with a lower risk of 40% eGFR decline. (Evaluating Comparative Effectiveness of Empagliflozin in Type 2 Diabetes Population With and Without Chronic Kidney Disease; NCT05465317).

Diagnostic and therapeutic challenges for PCPs regarding heart failure with preserved ejection fraction and obesity: results of an online internet-based survey.

BACKGROUND: Obesity (body mass index ≥ 30 kg/m2) is a major risk factor for heart failure with preserved ejection fraction (HFpEF) and affects most patients with HFpEF. Patients living with obesity may experience delays in HFpEF diagnosis and management. We aimed to understand the clinical journey of patients with obesity and HFpEF and the role of primary care providers (PCPs) in diagnosing and managing patients with both conditions. METHODS: An anonymous, US population-based online survey was conducted in September 2020 among 114 patients with self-reported HFpEF and obesity and 200 healthcare providers, 61 of whom were PCPs who treat patients with HFpEF and obesity. RESULTS: Half of patients (51%) with HFpEF reported waiting an average of 11 months to discuss their symptoms with a PCP; 11% then received their diagnosis from a PCP. PCPs initiated treatment and oversaw the management of HFpEF only 35% of the time, and 44% of PCPs discussed obesity treatment medication options with their patients. Only 20% of PCPs indicated they had received formal obesity management training, and 79% of PCPs indicated they would be interested in obesity management training and support. CONCLUSION: PCPs could play a valuable role in addressing obesity and referring patients with obesity and signs and symptoms of HFpEF to cardiologists. Increased awareness of HFpEF and its link to obesity may help PCPs more quickly identify and diagnose their patients with these conditions.

Heart failure with preserved ejection fraction (HFpEF) is a common form of heart failure. Many patients who have HFpEF also have obesity or excess weight. We wanted to understand the medical experience of patients with HFpEF and obesity and the role that primary care providers (PCPs) play in managing patients with these diseases. We surveyed 114 patients with HFpEF and obesity and 200 healthcare providers who treat patients with HFpEF and obesity, 61 of whom were PCPs. One-quarter of patients had a major heart-related event that led to their HFpEF diagnosis. Half of the patients said they had an initial discussion about HFpEF symptoms with a PCP, but only one in ten were diagnosed by a PCP. Few PCPs said they received obesity management training, but most were interested in receiving more obesity management training and support. PCPs play an important role in organizing care for patients with HFpEF and obesity. However, there is room to improve HFpEF awareness and access to obesity management tools and strategies among PCPs.

Trajectory of C-Reactive Protein and Incident Heart Failure in Black Adults: The Jackson Heart Study.

BACKGROUND: Increased hsCRP (high-sensitivity C-reactive protein), a marker of inflammation, is associated with incident cardiovascular events. We aim to determine whether the baseline or trajectory of hsCRP levels over time predicts incident heart failure (HF) hospitalization. METHODS: JHS (Jackson Heart Study) participants' (n=3920 Black adults) hsCRP levels were measured over 3 visits (from 2000 to 2013). We assessed the association of hsCRP at baseline (visit 1) with incident HF hospitalization using Cox proportional hazards models. Furthermore, we assessed the association of the trajectory of hsCRP over repeated measurements (visits 1-3) with incident HF using joint models. Hazard ratios are reflective of an increase in hsCRP by 1 SD on a log2 scale. We also assessed the association of change in hsCRP between visit 1 and visit 3 with Cox proportional hazards models by grouping patients by low (<2 mg/L) and high (≥2 mg/L) hsCRP levels. The 4 groups were low-to-low (referent), low-to-high, high-to-low, and high-to-high. RESULTS: Mean baseline age of participants was 54±13 years, and 63.8% were women. Over a median follow-up of 12 years, 308 (7.9%) participants were hospitalized with incident HF. Baseline hsCRP was not associated with incident HF (adjusted hazard ratio, 1.08 [95% CI, 0.96-1.22]). However, increasing hsCRP levels over repeated measures were associated with a higher risk of incident HF overall (adjusted hazard ratio, 1.22 [95% CI, 1.03-1.44]) and HF with preserved ejection fraction (adjusted hazard ratio, 1.30 [95% CI, 1.02-1.65]) but not HF with reduced ejection fraction (P>0.05). Furthermore, changes in hsCRP from low-to-high and high-to-low levels were associated with incident HF (P<0.05). CONCLUSIONS: While baseline hsCRP was not associated with incident HF, an increasing trajectory of hsCRP over time was associated with increased risk for incident HF (particularly HF with preserved ejection fraction). Temporal change in hsCRP may be an important marker of risk for incident HF with preserved ejection fraction in Black adults.

Ferric carboxymaltose and exercise capacity in heart failure with preserved ejection fraction and iron deficiency: the FAIR-HFpEF trial.

BACKGROUND AND AIMS: Evidence is lacking that correcting iron deficiency (ID) has clinically important benefits for patients with heart failure with preserved ejection fraction (HFpEF). METHODS: FAIR-HFpEF was a multicentre, randomized, double-blind trial designed to compare intravenous ferric carboxymaltose (FCM) with placebo (saline) in 200 patients with symptomatic HFpEF and ID (serum ferritin < 100 ng/mL or ferritin 100-299 ng/mL with transferrin saturation < 20%). The primary endpoint was change in 6-min walking test distance (6MWTD) from baseline to week 24. Secondary endpoints included changes in New York Heart Association class, patient global assessment, and health-related quality of life (QoL). RESULTS: The trial was stopped because of slow recruitment after 39 patients had been included (median age 80 years, 62% women). The change in 6MWTD from baseline to week 24 was greater for those assigned to FCM compared to placebo [least square mean difference 49 m, 95% confidence interval (CI) 5-93; P = .029]. Changes in secondary endpoints were not significantly different between groups. The total number of adverse events (76 vs. 114) and serious adverse events (5 vs. 19; rate ratio 0.27, 95% CI 0.07-0.96; P = .043) was lower with FCM than placebo. CONCLUSIONS: In patients with HFpEF and markers of ID, intravenous FCM improved 6MWTD and was associated with fewer serious adverse events. However, the trial lacked sufficient power to identify or refute effects on symptoms or QoL. The potential benefits of intravenous iron in HFpEF with ID should be investigated further in a larger cohort.

Patiromer-Facilitated Renin-Angiotensin-Aldosterone System Inhibitor Utilization in Patients With Heart Failure With or Without Comorbid Chronic Kidney Disease: Subgroup Analysis of DIAMOND Randomized Trial.

INTRODUCTION: Renin-angiotensin-aldosterone system inhibitor (RAASis; including mineralocorticoid receptor antagonists [MRAs]) benefits are greatest in patients with heart failure with reduced ejection fraction (HFrEF) and chronic kidney disease (CKD); however, the risk of hyperkalemia (HK) is high. METHODS: The DIAMOND trial (NCT03888066) assessed the ability of patiromer to control serum potassium (sK+) in patients with HFrEF with/without CKD. Prior to randomization (double-blind withdrawal, 1:1), patients on patiromer had to achieve ≥50% recommended doses of RAASi and 50 mg/day of MRA with normokalemia during a run-in period. The present analysis assessed the effect of baseline estimated glomerular filtration rate (eGFR) in subgroups of ≥/<60, ≥/<45 (prespecified), and ≥/<30 mL/min/1.73 m2 (added post hoc). RESULTS: In total, 81.3%, 78.9%, and 81.1% of patients with eGFR <60, <45, and <30 mL/min/1.73 m2 at screening achieved RAASi/MRA targets. A greater efficacy of patiromer vs placebo to control sK+ in patients with more advanced CKD was reported (p-interaction ≤ 0.027 for all eGFR subgroups). Greater effects on secondary endpoints were observed with patiromer vs placebo in patients with eGFR <60 and <45 mL/min/1.73 m2. Adverse effects were similar between patiromer and placebo across subgroups. CONCLUSION: Patiromer enabled use of RAASi, controlled sK+, and minimized HK risk in patients with HFrEF, with greater effect sizes for most endpoints noted in patient subgroups with lower eGFR. Patiromer was well tolerated by patients in all eGFR subgroups.

Optimal Medical Therapy and Outcomes Among Patients With Chronic Heart Failure With Reduced Ejection Fraction.

BACKGROUND: Optimal medical therapy (OMT) scoring may stratify clinical risk in real-world chronic heart failure with reduced ejection fraction (HFrEF) by integrating use and dosing of guideline-directed medical therapy (GDMT) for HFrEF. OBJECTIVES: The purpose of this study was to characterize patients and associated long-term clinical outcomes by OMT score-derived treatment groups. METHODS: CHAMP-HF (Change the Management of Patients with Heart Failure) included U.S. outpatients with chronic HFrEF receiving ≥1 GDMT. OMT subgroups were defined as suboptimal (score <3), acceptable (score = 3), and optimal (score ≥4) by baseline use and dose of GDMT, as proposed by the HF Collaboratory consortium. Cox proportional hazard analyses were used to assess for all-cause and cardiovascular death across subgroups, after adjusting for demographic and clinical covariates. RESULTS: The authors studied 4,582 participants enrolled in CHAMP-HF with available 2-year follow-up. Median age was 68 years, 1,327 (29%) were women, and 2,842 (62%) were White, non-Hispanic. Median OMT score across the population was 4 (Q1-Q3: 2-5), and 1,628 (35%) had suboptimal, 665 (14%) had acceptable, and 2,289 (50%) had optimal therapy. Participants with optimal treatment were younger, had higher annual household income, and were enrolled from practices with dedicated HF clinics (all P < 0.001) than participants with acceptable or suboptimal treatment. Participants with optimal treatment had lower all-cause death (adjusted HR: 0.77; 95% CI: 0.64-0.92) and cardiovascular death (adjusted HR: 0.79; 95% CI: 0.65-0.96) than those with suboptimal treatment. CONCLUSIONS: Across a large cohort of chronic ambulatory HFrEF, OMT scores stratified risk of all-cause and cardiovascular death.

Relationship between NT-proBNP, echocardiographic abnormalities and functional status in patients with subclinical siabetic cardiomyopathy.

INTRODUCTION: Persons with diabetes are at risk for developing a cardiomyopathy through several pathophysiological mechanisms independent of traditional risk factors for heart failure. Among those with diabetic cardiomyopathy (DbCM), the relationship between natriuretic peptides, cardiac structural abnormalities and functional capacity is largely unknown. METHODS: In this prespecified subgroup analysis of the Aldose Reductase Inhibition for Stabilization of Exercise Capacity in Heart Failure (ARISE-HF) trial, 685 participants with asymptomatic DbCM underwent baseline echocardiography data, laboratory investigations, and functional assessments. Participants were stratified by N-terminal pro-B type natriuretic peptide (NT-proBNP) quartiles, and correlation with echocardiographic and functional parameters were assessed using Spearman correlation test. RESULTS: The median NT-proBNP was 71 (Q1, Q3: 33, 135) ng/L. No association was observed between NT-proBNP concentrations and echocardiographic parameters of either diastolic or systolic dysfunction including global longitudinal strain, left ventricular ejection fraction, left ventricular mass index, left atrial volume index, E/E', or right ventricular systolic pressure. In contrast, NT-proBNP was significantly correlated with overall Kansas City Cardiomyopathy Questionnaire score (rho = - 0.10; p = 0.007), the Physical Activity Scale in the Elderly (rho = - 0.12; p = 0.004), duration of cardiopulmonary exercise testing (rho = - 0.28; p < 0.001), peak VO2 (rho = - 0.26; p < 0.001), and ratio of minute ventilation/carbon dioxide production (rho = 0.12; p = 0.002). After adjustment for known confounders, the correlation with Physical Activity Scale in the Elderly and overall Kansas City Cardiomyopathy Questionnaire score was no longer significant. CONCLUSION: Among patients with subclinical DbCM, elevated NT-proBNP concentrations are associated with worse health status, lower activity levels, and reduced functional capacity, but not with cardiac structural abnormalities. These findings suggest that regardless of cardiac structural abnormalities, biomarker concentrations reflect important deterioration in functional capacity in affected individuals. TRIAL REGISTRATION: ARISE-HF, NCT04083339 Date Registered August 23, 2019.

Associations of SGLT-2i with Cardiorenal Outcomes Among Diabetics with Prostate Cancer on Hormone Therapy.

Background: Studies have reported associations between prostate cancer, type II diabetes mellitus (T2DM) and cardiovascular disease in the context of treatment with hormone therapy (HT). This study aimed to assess the role of Sodium-Glucose Cotransporter-2 Inhibitors (SGLT2i) in preventing adverse cardiovascular and renal outcomes in diabetics with prostate cancer. Methods: Patients ≥ 18 years of age with T2DM and prostate cancer who received HT between August 1, 2013, and August 31, 2021, were identified using the TriNetX research network. Patients were divided into two cohorts based on treatment with SGLT2i or alternative antidiabetic therapies. The primary outcome was the composite of all-cause mortality, new onset heart failure (HF), acute myocardial infarction (MI), and peripheral artery disease over two years from HT initiation. Results: After propensity score matching, 2,155 patients remained in each cohort. The primary composite outcome occurred in 218 patients (16.1%) in the SGLT2i cohort versus 355 patients (26.3%) in the non-SGLT2i cohort (HR 0.689, 95% CI 0.582-0.816; p < 0.001). Furthermore, SGLT2i were associated with significantly lower odds of HF, HF exacerbation, peripheral artery disease, atrial fibrillation/flutter, cardiac arrest, need for renal replacement therapy, overall emergency room visits/hospitalizations and all-cause mortality. Conclusions: Use of SGLT2i for the treatment of T2DM among patients with prostate cancer on HT is associated with favorable cardiovascular, renal and all-cause mortality outcomes. This observation supports the hypothesis that a therapeutically relevant link exists between HT and cardiovascular disease in the context of prostate cancer.

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.

Racial Differences in Diabetic Cardiomyopathy: The ARISE-HF Trial.

BACKGROUND: Diabetic cardiomyopathy (DbCM) increases risk of overt heart failure in individuals with diabetes mellitus. Racial and ethnic differences in DbCM remain unexplored. OBJECTIVES: The authors sought to identify racial and ethnic differences among individuals with type 2 diabetes mellitus, structural heart disease, and impaired exercise capacity. METHODS: The ARISE-HF (Aldolase Reductase Inhibitor for Stabilization of Exercise Capacity in Heart Failure) trial is assessing the efficacy of an aldose reductase inhibitor for exercise capacity preservation in 691 persons with DbCM. Baseline characteristics, echocardiographic parameters, and functional capacity were analyzed and stratified by race and ethnicity. RESULTS: The mean age of the study participants was 67.4 years; 50% were women. Black and Hispanic patients had lower use of diabetes mellitus treatments. Black patients had poorer baseline ventricular function and more impaired global longitudinal strain. Overall, health status was preserved, based on Kansas City Cardiomyopathy Questionnaire scores, but reduced exercise capacity was present as evidenced by reduced Physical Activity Scale for the Elderly (PASE) scores. When stratified by race and ethnicity and compared with the entire cohort, Black patients had poorer health status, more reduced physical activity, and a greater impairment in exercise capacity during cardiopulmonary exercise testing, whereas Hispanic patients also displayed compromised cardiopulmonary exercise testing functional capacity. White patients demonstrated higher physical activity and functional capacity. CONCLUSIONS: Racial and ethnic differences exist in baseline characteristics of persons affected by DbCM, with Black and Hispanic study participants demonstrating higher risk features. These insights inform the need to address differences in the population with DbCM. (Safety and Efficacy of AT-001 in Patients With Diabetic Cardiomyopathy [ARISE-HF]; NCT04083339).

Efficacy and safety of SGLT2 inhibitors with and without glucagon-like peptide 1 receptor agonists: a SMART-C collaborative meta-analysis of randomised controlled trials.

BACKGROUND: SGLT2 inhibitors and GLP-1 receptor agonists both improve cardiovascular and kidney outcomes in patients with type 2 diabetes. We sought to evaluate whether the benefits of SGLT2 inhibitors are consistent in patients receiving and not receiving GLP-1 receptor agonists. METHODS: We conducted a collaborative meta-analysis of trials included in the SGLT2 Inhibitor Meta-Analysis Cardio-Renal Trialists' Consortium, restricted to participants with diabetes. Treatment effects from individual trials were obtained from Cox regression models and pooled using inverse variance weighted meta-analysis. The two main cardiovascular outcomes assessed included major adverse cardiovascular events (nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death), and hospitalisation for heart failure or cardiovascular death. The main kidney outcomes assessed were chronic kidney disease progression (≥40% decline in estimated glomerular filtration rate [eGFR], kidney failure [eGFR <15 mL/min/1·73 m2, chronic dialysis, or kidney transplantation], or death due to kidney failure), and the rate of change in eGFR over time. Safety outcomes were also assessed. FINDINGS: Across 12 randomised, double-blind, placebo-controlled trials, 3065 (4·2%) of 73 238 participants with diabetes were using GLP-1 receptor agonists at baseline. SGLT2 inhibitors reduced the risk of major adverse cardiovascular events in participants both receiving and not receiving GLP-1 receptor agonists (hazard ratio [HR] 0·81, 95% CI 0·63-1·03 vs 0·90, 0·86-0·94; p-heterogeneity=0·31). Effects on hospitalisation for heart failure or cardiovascular death (0·76, 0·57-1·01 vs 0·78, 0·74-0·82; p-heterogeneity=0·90) and chronic kidney disease progression (0·65, 0·46-0·94 vs 0·67, 0·62-0·72; p-heterogeneity=0·81) were also consistent regardless of GLP-1 receptor agonist use, as was the effect on the chronic rate of change in eGFR over time (heterogeneity=0·92). Fewer serious adverse events occurred with SGLT2 inhibitors compared with placebo, irrespective of GLP-1 receptor agonist use (relative risk 0·87, 95% CI 0·79-0·96 vs 0·91, 0·89-0·93; p-heterogeneity=0·41). INTERPRETATION: The effects of SGLT2 inhibitors on cardiovascular and kidney outcomes are consistent regardless of the background use of GLP-1 receptor agonists. These findings suggest independent effects of these evidence-based therapies and support clinical practice guidelines recommending the use of these agents in combination to improve cardiovascular and kidney metabolic outcomes. FUNDING: National Health and Medical Research Council of Australia and the Ramaciotti Foundation.

Increased Spironolactone Dosing in Acute Heart Failure Alters Potassium Homeostasis but Does not Enhance Decongestion.

BACKGROUND: The ATHENA-HF (Aldosterone Targeted Neurohormonal Combined with Natriuresis Therapy in Heart Failure) clinical trial found no improvements in natriuretic peptide levels or clinical congestion when spironolactone 100 mg/day for 96 hours was used in addition to usual treatment for acute heart failure. METHODS: We performed a post hoc analysis of ATHENA-HF to determine whether spironolactone treatment induced any detectable pharmacodynamic effects and whether patients with potentially greater aldosterone activity experienced additional decongestion. Trial subjects previously treated with spironolactone were excluded. We first examined for changes in renal potassium handling. Using the baseline serum potassium level as a surrogate marker of spironolactone activity, we then divided each treatment arm into tertiles of baseline serum potassium and explored for differences in laboratory and clinical congestion outcomes. RESULTS: Among spironolactone-naïve patients, the change in serum potassium did not differ after 24 hours or 48 hours but was significantly greater with spironolactone treatment compared to placebo at 72 hours (0.23 ± 0.55 vs 0.03 ± 0.60 mEq/L; P = 0.042) and 96 hours (0.32 ± 0.51 vs 0.13 ± 0.72 mEq/L; P = 0.046). Potassium supplementation was similar at treatment start and at 24 hours, but spironolactone-treated patients required substantially less potassium replacement at 48 hours (24% vs 36%; P = 0.048), 72 hours (21% vs 37%; P = 0.013), and 96 hours (11% vs 38%; P < 0.001). When the treatment arms were divided into tertiles of baseline serum potassium, there were no differences in the 96-hour log N-terminal pro-B-type natriuretic peptide levels, net fluid loss, urine output, or dyspnea relief in any of the potassium groups, with no effect modification by treatment exposure. CONCLUSIONS: Spironolactone 100 mg/day for 96 hours in patients receiving intravenous loop diuresis for acute heart failure has no clear added decongestive ability but does meaningfully limit potassium wasting.

Association of Medication Adherence and Health Status in Heart Failure With Reduced Ejection Fraction: Insights From the CHAMP-HF Registry.

BACKGROUND: The foundation for managing heart failure with reduced ejection fraction (HFrEF) is adherence to guideline-directed medical therapy. Finding an association between medication adherence and patients' health status (their symptoms, function, and quality of life) can be used to underscore its importance to patients. METHODS: The association of self-reported medication adherence in US outpatients with HFrEF enrolled in the Change the Management of Patients with Heart Failure registry from 2015 to 2017 was compared with their health status at baseline and 12 months later. A secondary analysis of changes in adherence between baseline and 6 months with 6-month health status was also performed. Medication adherence was assessed with the self-reported 4-item Morisky-Green-Levine Medication Adherence Scale, with scores ≥1 classified as nonadherent. The primary health status outcome was the disease-specific 12-item Kansas City Cardiomyopathy Questionnaire Overall Summary Score (KCCQ-OS; range, 0-100; higher is better). Robust linear regression models adjusted for confounders were used. RESULTS: After excluding those who died (n=316) or did not provide 12-month KCCQ (n=1285), 3495 outpatients with HFrEF were included, of whom 1108 (31.7%) reported being nonadherent. Nonadherent participants were younger, had significantly worse baseline health status (-5.83-point difference; P<0.001), and showed less improvement at 12 months (-1.7-point difference in mean change; P=0.017) than adherent participants. Among nonadherent patients at baseline, those whose adherence improved trended toward greater 6-month health status improvements than those remaining nonadherent (fully adjusted difference of 2.52 points; P=0.054). CONCLUSIONS: In HFrEF, medication nonadherence was associated with worse health status and less improvement over the following year. Improvements in adherence were associated with better health status than remaining nonadherent, underscoring the importance of supporting adherence with guideline-directed medical therapy in patients with HFrEF.

Blood Volume Analysis and Cardio-renal syndrome: from bench to bedside.

BACKGROUND: This review delves into the intricate landscape of cardiorenal syndrome (CRS) and highlights the pivotal role of Blood Volume Analysis (BVA) in improving patient care and outcomes. SUMMARY: BVA offers a direct and highly accurate quantification of intravascular volume, red blood cell volume, and plasma volume, complete with patient-specific norms. This diagnostic tool enhances the precision of diuretic and red cell therapies, significantly elevating the effectiveness of conventional care. KEY MESSAGES: · Comprehensive Understanding: Our objectives encompass a comprehensive understanding of how BVA informs the evaluation and treatment of CRS, including its subtypes, pathophysiology, and clinical significance. · BVA Principles and Advantages: We delve into BVA principles, techniques, and measurements, elucidating its diagnostic potential and advantages compared to commonly used surrogate measures. · Clinical Relevance: We dissect the clinical relevance of BVA in various CRS scenarios, emphasizing its unique contributions to each subtype. · Improving patient outcomes: By assessing the tangible impact of BVA on patient outcomes through meticulous analysis of relevant clinical studies, we unveil its potential to enhance health outcomes and optimize resource utilization. · Multidisciplinary Collaboration: Acknowledging the challenges and limitations associated with BVA's clinical implementation, we underscore the importance of multidisciplinary collaboration among cardiologists, nephrologists, and other clinicians. · Future Directions: Finally, we identify research gaps and propose future directions for BVA and CRS, contributing to ongoing advancements in this field and patients affected by this complicated clinical syndrome.

A Patch Wearable Cardioverter-Defibrillator for Patients at Risk of Sudden Cardiac Arrest.

BACKGROUND: For many patients, sudden cardiac arrest (SCA) risk is elevated temporarily. Wearable cardioverter-defibrillators (WCDs) can monitor and treat SCA during these temporary periods. Traditional WCDs can be uncomfortable, require frequent maintenance, and cannot be used when showering, resulting in poor compliance and avoidable SCA deaths. The Jewel is a novel, water-resistant patch-wearable cardioverter-defibrillator (P-WCD) with a machine learning detection algorithm designed to improve compliance and protection against SCA. OBJECTIVES: This study aims to demonstrate the safety and clinical effectiveness of a novel P-WCD. METHODS: The Jewel IDE Study, a prospective, single-arm study conducted at 30 U.S. sites, enrolled patients at SCA risk due to ventricular tachycardia/ventricular fibrillation who were not candidates for or refused an implantable defibrillator. The primary safety endpoint was <15% patients with clinically significant cutaneous adverse device effects and the primary effectiveness endpoint was <2 inappropriate shocks/100 patient-months. Secondary endpoints were ≥1 successful ventricular tachycardia/ventricular fibrillation conversion and wear time compliance of >14.1 h/d. RESULTS: A total of 305 patients (mean age: 57.9 years; 30.2% female, 27.9% non-White) were enrolled, of which 290 had available device data. The clinically significant cutaneous adverse device effect rate was 2.30% (upper 1-sided 98% CI: 4.80); none were severe. No device-related deaths or serious adverse events were reported. The inappropriate shock rate was 0.36/100 patient-months (upper 1-sided 98% CI: 1.53). Of 11 shocks in 9 patients, 9 shocks were adjudicated to be appropriate. Eight of 9 shocks were successful with a single shock. Median wear time compliance was 23.5 (20.7-23.9) h/d. CONCLUSIONS: The novel P-WCD is a safe and effective WCD with high patient compliance. There were no deaths due to noncompliance and a high number of successful conversions (Jewel IDE study [A Clinical Evaluation of the Jewel P-WCD in Subjects at High Risk for Sudden Cardiac Arrest]; NCT05201495).

Summary and Panel Discussion.

In this video, Javed Butler, MD, Jonathan Rich, MD, Rachel Pessah-Pollack, MD, and John E. Anderson, MD, summarize the key points of the enhanced publication "Role of SGLT2 Inhibitors in the Management of Heart Failure With and Without Type 2 Diabetes." The panel then delves deeper into some of the topics raised.