Heart Failure/Transplantation
RCT: Sodium Zirconium Cyclosilicate Improves Spironolactone Uptitration in HFrEF but Raises Concern for Increased HF Events
28 Jan, 2025 | 10:00h | UTCBackground: Hyperkalemia remains a major barrier to optimal use of mineralocorticoid receptor antagonists (MRAs) in patients with heart failure and reduced ejection fraction (HFrEF). While MRAs significantly reduce morbidity and mortality, real-world data show that fears surrounding hyperkalemia often lead to MRA down-titration or discontinuation. Sodium zirconium cyclosilicate (SZC), a newer oral potassium binder, has shown promise in managing hyperkalemia. However, its impact on MRA optimization and clinical outcomes in HFrEF has not been fully established.
Objective: To determine whether SZC can enable optimal dosing of spironolactone (≥25 mg/day) by preventing hyperkalemia in patients with symptomatic HFrEF, and to assess potential effects on heart failure outcomes.
Methods: This prospective, double-blind, randomized-withdrawal trial (REALIZE-K) enrolled adult patients with left ventricular ejection fraction ≤40% (NYHA class II-IV), on guideline-directed medical therapy but not on a full-dose MRA due to either prevalent hyperkalemia (serum potassium [K⁺] 5.1-5.9 mEq/L) or high hyperkalemia risk. During an open-label run-in, spironolactone was up-titrated (target 50 mg/day), and participants with hyperkalemia received SZC. Only those who achieved normokalemia (3.5-5.0 mEq/L) on spironolactone ≥25 mg/day continued into a 6-month randomized-withdrawal phase (SZC vs placebo). The primary endpoint was maintenance of normokalemia while on ≥25 mg/day spironolactone without rescue therapy for hyperkalemia. Key secondary outcomes included the time to first hyperkalemia event, time to spironolactone dose reduction/discontinuation due to hyperkalemia, and changes in health-related quality of life (Kansas City Cardiomyopathy Questionnaire–Clinical Summary Score).
Results: A total of 203 participants were randomized (SZC: n=102; placebo: n=101). SZC significantly increased the proportion of participants who maintained normokalemia on ≥25 mg/day spironolactone (71% vs 36%; OR: 4.45; 95% CI: 2.89-6.86; p<0.001). Rates of hyperkalemia were also lower with SZC (HR: 0.51; 95% CI: 0.37-0.71; p<0.001), and fewer patients required spironolactone down-titration or discontinuation (HR: 0.37; 95% CI: 0.17-0.73; p=0.006). There was no difference in KCCQ-Clinical Summary Score between groups (p=0.72). Notably, more participants in the SZC arm had adjudicated heart failure events (10 vs 2 in placebo) over the 6-month period, although the trial was not powered to detect differences in clinical outcomes.
Conclusions: In patients with symptomatic HFrEF and prevalent or incident hyperkalemia, sodium zirconium cyclosilicate (SZC) successfully enabled higher spironolactone doses by maintaining potassium levels in the normal range. However, the increased rate of heart failure (HF) events in the SZC group raises concern, particularly given the study’s limited power for clinical outcomes and baseline imbalances favoring higher HF risk in the SZC group (older age, lower eGFR, higher NT-proBNP). Although these findings do not establish a definitive causal relationship, they underscore a possible risk of fluid retention and the importance of cautious use in higher-risk populations. Larger, event-driven trials are crucial to confirm whether SZC-related sodium exchange may exacerbate HF decompensation despite the benefits of more effective MRA therapy.
Implications for Practice: SZC offers clinicians a means to sustain or escalate spironolactone dosing in hyperkalemia-prone HFrEF patients who would otherwise face MRA discontinuation. Still, the unexpected signal of increased HF events highlights the need for vigilant patient selection, fluid status monitoring, and regular follow-up. Clinicians should balance the advantages of maintaining guideline-recommended MRA doses against potential costs, the patient’s baseline HF severity, and possible sodium retention. Individualized care, particularly in older patients or those with high NT-proBNP levels, remains critical until more robust outcome data are available.
Study Strengths and Limitations: Strengths include strict definitions of hyperkalemia, a rigorous protocol for titrating spironolactone and SZC, and high rates of concurrent guideline-directed therapies. Limitations encompass the modest sample size, short follow-up period, and imbalance in baseline risk factors favoring the placebo group. Also, the study was not powered for major clinical events, limiting interpretability of the heart failure outcome signals.
Future Research: Further large-scale, long-term investigations are needed to clarify whether the higher incidence of HF events seen with SZC reflects underlying population differences or a genuine treatment-related risk. Such studies should prioritize hard clinical endpoints (eg, HF hospitalization, cardiovascular mortality), capture real-world tolerability data, and incorporate cost-effectiveness analyses. Research into the mechanisms of sodium exchange in compromised HF patients may also help identify subgroups that stand to gain the most from potassium-binding strategies or, conversely, experience undue risk.
Reference: Kosiborod MN, Cherney DZI, Desai AS, et al. “Sodium Zirconium Cyclosilicate for Management of Hyperkalemia During Spironolactone Optimization in Patients With Heart Failure.” Journal of the American College of Cardiology. 2025; DOI: https://doi.org/10.1016/j.jacc.2024.11.014
Review: Heart Failure with Preserved Ejection Fraction
9 Jan, 2025 | 11:42h | UTCIntroduction: This summary reviews the 2025 New England Journal of Medicine article by Antonio Cannata, M.D., and Theresa A. McDonagh, M.D., which addresses the clinical syndrome of heart failure with preserved ejection fraction (HFpEF). The document describes its heterogeneous nature, diagnostic challenges, and emerging therapeutic approaches. Key objectives include emphasizing the importance of ruling out mimickers (e.g., respiratory disease or amyloidosis) and reviewing the evidence for guideline-directed therapies that reduce hospitalizations and improve quality of life.
Key Recommendations:
- Diagnostic Steps:
- Confirm an ejection fraction ≥50% and evidence of diastolic dysfunction or raised filling pressures.
- Exclude confounding conditions (e.g., COPD, hypertrophic cardiomyopathy, cardiac amyloidosis) through imaging (echocardiography, cardiac MRI) and relevant laboratory tests (natriuretic peptides).
- Consider invasive hemodynamic assessment if the diagnosis remains unclear.
- Initial Management:
- Diuretics: Use loop diuretics or thiazides to relieve congestion and peripheral edema. Titrate to the lowest effective dose once euvolemia is achieved.
- Blood Pressure and Comorbidity Control: Optimize antihypertensive therapy with agents such as renin–angiotensin–system (RAS) inhibitors or mineralocorticoid receptor antagonists (MRAs) to address underlying hypertension and other cardiovascular risk factors.
- Specific Pharmacotherapies:
- SGLT2 Inhibitors: Empagliflozin and dapagliflozin reduce the composite risk of cardiovascular death or heart-failure hospitalization, primarily by lowering hospitalization rates.
- RAS Blockade (ACE Inhibitors/ARBs/ARNIs): Although large trials did not show a clear mortality benefit, some studies indicated fewer hospitalizations.
- MRAs (e.g., Spironolactone, Finerenone): Evidence for HFpEF is mixed, though a recent trial (FINEARTS-HF) supports the potential role of finerenone in reducing hospitalization in patients with left ventricular ejection fraction ≥40%.
- GLP-1 Receptor Agonists: Agents like semaglutide (and the dual GIP/GLP-1 agonist tirzepatide) showed improvements in weight reduction, exercise tolerance, and quality of life in patients with HFpEF and obesity, suggesting an emerging cardiometabolic strategy.
- Beta-Blockers: Widespread use in HFpEF often relates to other comorbidities, but trials have not demonstrated significant outcome benefits specifically for preserved ejection fraction.
- Adjunct Therapies and Devices:
- Pulmonary Artery Pressure Monitoring (CardioMEMS): Can help guide diuretic adjustments and has shown reductions in hospitalizations for heart failure across ejection-fraction ranges.
- Interatrial Shunt Devices: Trials so far have not shown conclusive benefits and may pose increased risk in patients with higher ejection fractions.
- Lifestyle and Comorbidity Management:
- Address obesity, type 2 diabetes, and physical inactivity through dietary and exercise interventions.
- Evaluate for sleep-disordered breathing, as optimizing respiratory status can improve symptoms and reduce hospitalizations.
Conclusion: HFpEF is a complex syndrome often associated with obesity, hypertension, and other coexisting conditions that contribute to clinical variability. While no single agent has definitively reduced mortality, trials have shown meaningful reductions in hospitalizations and improvements in quality of life, especially with SGLT2 inhibitors and, in obese patients, GLP-1 receptor agonists. Ongoing research into pathophysiology-driven therapies may enhance future outcomes. For now, clinicians should employ a multimodal approach targeting volume status, cardiometabolic health, and comorbidity control to optimize management.
Reference:
Cannata A, McDonagh TA. Heart Failure with Preserved Ejection Fraction. New England Journal of Medicine. 2025;392:173–184.
DOI: https://doi.org/10.1056/NEJMcp2305181
RCT: Tirzepatide Reduces Heart Failure Events and Improves Health Status in Obese HFpEF Patients
16 Nov, 2024 | 16:42h | UTCBackground: Obesity significantly increases the risk of heart failure with preserved ejection fraction (HFpEF) due to visceral adiposity-induced systemic inflammation affecting the myocardium. Tirzepatide, a dual agonist of glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) receptors, induces substantial weight loss. However, its effects on cardiovascular outcomes in obese HFpEF patients were previously unknown.
Objective: To assess the impact of tirzepatide on cardiovascular events and health status in patients with HFpEF and obesity.
Methods: In this international, double-blind, randomized, placebo-controlled trial, 731 patients with HFpEF (ejection fraction ≥50%), a body-mass index (BMI) of at least 30, and New York Heart Association class II–IV symptoms were assigned to receive tirzepatide (up to 15 mg subcutaneously once weekly) or placebo for at least 52 weeks. The two primary endpoints were the composite of adjudicated death from cardiovascular causes or worsening heart-failure events, and the change from baseline to 52 weeks in the Kansas City Cardiomyopathy Questionnaire clinical summary score (KCCQ-CSS).
Results: Over a median follow-up of 104 weeks, death from cardiovascular causes or worsening heart-failure events occurred in 9.9% of patients in the tirzepatide group versus 15.3% in the placebo group (hazard ratio [HR], 0.62; 95% confidence interval [CI], 0.41 to 0.95; P=0.026). Worsening heart-failure events occurred in 8.0% with tirzepatide versus 14.2% with placebo (HR, 0.54; 95% CI, 0.34 to 0.85). At 52 weeks, the mean increase in KCCQ-CSS was 19.5 points in the tirzepatide group compared to 12.7 points in the placebo group (between-group difference, 6.9; 95% CI, 3.3 to 10.6; P<0.001). Adverse events leading to discontinuation occurred in 6.3% of tirzepatide patients versus 1.4% of placebo patients, mainly due to gastrointestinal symptoms.
Conclusions: Tirzepatide significantly reduced the risk of cardiovascular death or worsening heart failure and improved health status in patients with HFpEF and obesity.
Implications for Practice: These findings suggest that tirzepatide may be an effective therapeutic option for reducing heart failure events and enhancing quality of life in obese patients with HFpEF. Its benefits may be attributed to significant weight loss and anti-inflammatory effects, offering a potential new approach in managing this patient population.
Study Strengths and Limitations: Strengths include the randomized, double-blind design and a long median follow-up of 104 weeks. Limitations involve the exclusion of patients with BMI less than 30, which may limit applicability to non-obese HFpEF patients with increased visceral adiposity. Additionally, the higher rate of gastrointestinal adverse events leading to discontinuation in the tirzepatide group warrants cautious consideration.
Future Research: Further studies are needed to evaluate tirzepatide’s effects in HFpEF patients with lower BMI but increased visceral adiposity and to elucidate the mechanisms underlying its cardiovascular benefits.
RCT: Preemptive TAVR Does Not Improve Composite Outcomes but May Improve Quality of Life in HFrEF Patients with Moderate Aortic Stenosis
10 Nov, 2024 | 14:18h | UTCBackground: Heart failure with reduced ejection fraction (HFrEF) management emphasizes neurohormonal modulation and afterload reduction. Moderate aortic stenosis (AS) increases afterload, potentially worsening outcomes in HFrEF patients. While transcatheter aortic valve replacement (TAVR) is established for severe AS, its benefit in moderate AS remains uncertain.
Objective: To determine whether TAVR provides clinical benefits over guideline-directed medical therapy (GDMT) in patients with HFrEF and moderate AS.
Methods: In the TAVR UNLOAD randomized controlled trial, 178 symptomatic HFrEF patients (left ventricular ejection fraction 20%-50%) on GDMT with moderate AS were randomized 1:1 to receive TAVR with a balloon-expandable valve or clinical AS surveillance (CASS) with aortic valve replacement upon progression to severe AS. The primary endpoint was the hierarchical occurrence of: (1) all-cause death; (2) disabling stroke; (3) disease-related hospitalizations and heart failure equivalents; and (4) change from baseline in the Kansas City Cardiomyopathy Questionnaire Overall Summary Score (KCCQ-OSS).
Results: The mean age was 77 years, 20.8% were female, and 55.6% were in NYHA class III or IV. Median follow-up was 23 months. In the CASS group, 43% underwent TAVR due to progression to severe AS at a median of 12 months. TAVR was not superior to CASS for the primary endpoint (win ratio 1.31; 95% CI: 0.91-1.88; P = 0.14). However, at 1 year, TAVR resulted in a greater improvement in KCCQ-OSS compared with CASS (12.8 ± 21.9 vs 3.2 ± 22.8 points; P = 0.018). There were no significant differences in all-cause mortality or major adverse events between groups.
Conclusions: In HFrEF patients with moderate AS on GDMT, TAVR was not superior to clinical surveillance for the primary composite endpoint but was associated with improved quality of life at 1 year.
Implications for Practice: Preemptive TAVR may offer quality-of-life benefits in select symptomatic HFrEF patients with moderate AS but does not reduce mortality or major cardiovascular events compared to surveillance. Clinicians should weigh patient-specific factors when considering TAVR for moderate AS.
Study Strengths and Limitations: Strengths include being the first randomized trial assessing TAVR in moderate AS with HFrEF. Limitations involve being underpowered due to slow enrollment and protocol changes, and a high crossover rate (43% in the CASS group underwent TAVR), potentially attenuating differences between groups.
Future Research: Larger, adequately powered trials are needed to confirm these findings and identify patients who may benefit most from preemptive TAVR in moderate AS.
Guideline Summary: Sodium-Glucose Cotransporter-2 (SGLT-2) Inhibitors for Adults with Chronic Kidney Disease
4 Oct, 2024 | 11:14h | UTCIntroduction
A recent clinical practice guideline published in The BMJ titled “Sodium-glucose cotransporter-2 (SGLT-2) inhibitors for adults with chronic kidney disease” provides evidence-based recommendations on the use of SGLT-2 inhibitors in adults with chronic kidney disease (CKD), regardless of diabetes status. The guideline aims to assist clinicians in making informed decisions to improve patient outcomes in CKD management.
Key Recommendations and Patient Care Implications
- Risk Stratification
- Assessment: Patients with CKD should be stratified based on their risk of disease progression and complications using estimated glomerular filtration rate (eGFR) and albuminuria levels, following the Kidney Disease Improving Global Outcomes (KDIGO) classification.
- Clinical Implication: Proper risk stratification guides the intensity of treatment and monitoring.
- Use of SGLT-2 Inhibitors
- Low to Moderate Risk Patients: For adults at low or moderate risk, the guideline suggests administering SGLT-2 inhibitors (weak recommendation in favor).
- Patient Care Impact: Clinicians should discuss potential benefits and risks with patients, considering individual preferences.
- High to Very High Risk Patients: For adults at high or very high risk, a strong recommendation is made to administer SGLT-2 inhibitors.
- Patient Care Impact: Clinicians should prioritize initiating SGLT-2 inhibitors in these patients to reduce risks of mortality and progression to kidney failure.
- Low to Moderate Risk Patients: For adults at low or moderate risk, the guideline suggests administering SGLT-2 inhibitors (weak recommendation in favor).
- Benefits of SGLT-2 Inhibitors
- Outcomes: Reduction in all-cause mortality, cardiovascular mortality, hospitalization for heart failure, kidney failure, non-fatal myocardial infarction, and non-fatal stroke.
- Clinical Implication: SGLT-2 inhibitors provide significant protective effects on cardiovascular and kidney health in CKD patients.
- Potential Harms and Monitoring
- Adverse Effects: Minimal increase in risks of acute kidney injury requiring dialysis, bone fractures, lower limb amputations, ketoacidosis, genital infections, or symptomatic hypovolemia.
- Patient Counseling: Patients should be informed about possible side effects and advised on when to seek medical attention.
- Monitoring: Routine laboratory monitoring is not generally necessary, except in high-risk individuals.
- Practical Considerations for Prescribing
- Initiation: Start SGLT-2 inhibitors in patients with eGFR ≥20 mL/min/1.73 m².
- Continuation: Medications can be continued even if eGFR falls below 20 mL/min/1.73 m² until dialysis is initiated.
- Dosage: Initiate at the highest possible dose without the need for titration.
- Drug Selection: Canagliflozin, dapagliflozin, and empagliflozin are suitable options.
- Concurrent Medications: Review and adjust diuretics to prevent volume depletion.
- Patient Education and Self-Management
- Sick Day Rules: Advise patients to temporarily discontinue SGLT-2 inhibitors during acute illnesses causing dehydration.
- Lifestyle Modifications: Encourage adherence to medication and healthy lifestyle changes to enhance treatment efficacy.
- Applicability and Exceptions
- Applicable Populations: Recommendations apply broadly to adults with CKD, with or without type 2 diabetes.
- Exceptions: Caution or alternative approaches may be necessary for patients:
- Receiving kidney replacement therapy.
- With kidney transplants, polycystic kidney disease, rare kidney diseases.
- With eGFR <20 mL/min/1.73 m² not on replacement therapy.
Conclusion
The guideline underscores the importance of incorporating SGLT-2 inhibitors into the management plan for adults with CKD to improve survival and reduce cardiovascular and kidney-related complications. Clinicians should evaluate each patient’s risk profile and engage in shared decision-making to optimize treatment outcomes.
Polled Analysis: Semaglutide Reduces Heart Failure Events in Obese Patients with HFpEF
12 Sep, 2024 | 13:39h | UTCStudy Design and Population: This post-hoc pooled analysis combined data from four randomized, placebo-controlled trials (SELECT, FLOW, STEP-HFpEF, and STEP-HFpEF DM) involving 3,743 participants with heart failure and preserved or mildly reduced ejection fraction (HFpEF). The participants had various comorbidities including obesity, diabetes, and atherosclerotic cardiovascular disease. They were randomized to receive either semaglutide or placebo.
Main Findings: Semaglutide significantly reduced the risk of the composite endpoint of cardiovascular death or worsening heart failure events compared to placebo (HR 0.69, 95% CI 0.53–0.89, p=0.0045). It also reduced worsening heart failure events alone (HR 0.59, 95% CI 0.41–0.82, p=0.0019). However, no significant reduction in cardiovascular death alone was observed (HR 0.82, 95% CI 0.57–1.16, p=0.25). Semaglutide was generally well tolerated, with fewer serious adverse events compared to placebo.
Implications for Practice: These findings suggest semaglutide may be an effective therapy to reduce heart failure-related events in obese patients with HFpEF. Although semaglutide did not reduce cardiovascular death, its ability to lower the risk of heart failure hospitalizations makes it a potential therapeutic option for managing HFpEF in this population, a condition with limited treatment choices.
Cohort Study: Lower Risk of Cardiovascular Complications in Post–COVID-19 Vaccine Myocarditis Compared to Conventional Etiologies
7 Sep, 2024 | 20:36h | UTCStudy Design and Population: This French nationwide cohort study included 4,635 individuals aged 12-49 hospitalized for myocarditis between December 2020 and June 2022. The cohort was divided into three groups: 558 patients with post–COVID-19 mRNA vaccine myocarditis, 298 with post–COVID-19 infection myocarditis, and 3,779 with conventional myocarditis.
Main Findings: At 18 months of follow-up, the frequency of cardiovascular events was significantly lower in the postvaccine myocarditis group (5.7%) compared to conventional myocarditis (13.2%) with a weighted hazard ratio (wHR) of 0.55 (95% CI, 0.36-0.86). Hospital readmission for myopericarditis occurred in 3.2% of postvaccine cases, 4.0% of post–COVID-19 cases, and 5.8% of conventional cases. The all-cause mortality rate was 0.2% for postvaccine myocarditis, 1.3% for post–COVID-19 myocarditis, and 1.3% for conventional myocarditis.
Implications for Practice: Postvaccine myocarditis patients, primarily young males, experience fewer complications compared to conventional myocarditis, but long-term follow-up is still needed. These findings should guide future mRNA vaccine recommendations and clinical management for myocarditis patients.
Reference: Semenzato L. et al. (2024). Long-term Prognosis of Myocarditis Attributed to COVID-19 mRNA Vaccination, SARS-CoV-2, or Conventional Etiologies. JAMA, Online. DOI: http://doi.org/10.1001/jama.2024.16380
Link: https://jamanetwork.com/journals/jama/fullarticle/2822933
RCT: Finerenone Reduces Worsening Heart Failure Events in Patients with Mildly Reduced or Preserved Ejection Fraction
6 Sep, 2024 | 22:03h | UTCStudy Design and Population: This international, double-blind, randomized clinical trial included 6,001 patients with heart failure and a left ventricular ejection fraction of 40% or greater. Patients were randomly assigned to receive either finerenone (20 mg or 40 mg daily) or placebo in addition to standard therapy, with a median follow-up period of 32 months.
Main Findings: The finerenone group experienced a 16% reduction in the composite primary outcome of worsening heart failure events and death from cardiovascular causes compared to placebo (rate ratio, 0.84; 95% CI, 0.74 to 0.95; P=0.007). Specifically, total worsening heart failure events were lower in the finerenone group (rate ratio, 0.82; 95% CI, 0.71 to 0.94; P=0.006), but cardiovascular mortality did not significantly differ between the groups (hazard ratio, 0.93; 95% CI, 0.78 to 1.11). Finerenone was linked to an increased risk of hyperkalemia.
Implications for Practice: Finerenone reduces worsening heart failure events in patients with mildly reduced or preserved ejection fraction, making it a viable addition to standard heart failure therapy. However, clinicians should monitor for hyperkalemia, a known side effect, and the lack of significant mortality benefit highlights the need for further investigation into long-term cardiovascular outcomes.
RCT: Vutrisiran Reduces Mortality and Cardiovascular Events in Patients with Transthyretin Amyloidosis Cardiomyopathy
6 Sep, 2024 | 21:57h | UTCStudy Design and Population: This double-blind, randomized clinical trial evaluated the efficacy of vutrisiran in 655 patients with transthyretin amyloidosis with cardiomyopathy (ATTR-CM). Participants were randomly assigned to receive either vutrisiran (25 mg) or placebo every 12 weeks for up to 36 months. The study population included patients both with and without baseline tafamidis treatment.
Main Findings: Vutrisiran treatment significantly reduced the risk of death from any cause and recurrent cardiovascular events compared to placebo (HR: 0.72, 95% CI: 0.56–0.93, p=0.01). In monotherapy patients (no tafamidis), the hazard ratio was 0.67 (95% CI: 0.49–0.93, p=0.02). Vutrisiran also preserved physical function, showing less decline in the 6-minute walk test distance (mean difference: 26.5 meters, p<0.001) and quality of life (mean KCCQ-OS difference: 5.8 points, p<0.001). Adverse events were comparable between groups.
Implications for Practice: Vutrisiran offers a promising treatment option for reducing mortality, cardiovascular events, and functional decline in ATTR-CM patients. Its favorable safety profile supports its potential use in long-term management.
RCT: Beta-Blocker Interruption Post-Myocardial Infarction Increases Cardiovascular Events Without Improving Quality of Life – N Engl J Med
31 Aug, 2024 | 19:04h | UTCStudy Design and Population: This multicenter, open-label, randomized, noninferiority trial included 3,698 patients across 49 sites in France. Participants had a history of myocardial infarction, a left ventricular ejection fraction of at least 40%, and had not experienced a cardiovascular event in the past six months. The study compared outcomes between patients who either interrupted or continued long-term beta-blocker therapy, with a minimum follow-up of one year.
Main Findings: Interruption of beta-blocker treatment resulted in a higher incidence of adverse cardiovascular events (23.8%) compared to continuation (21.1%), with a hazard ratio of 1.16 (95% CI, 1.01 to 1.33). The difference did not meet the criteria for noninferiority (P=0.44). Additionally, there was no significant improvement in quality of life among patients who discontinued beta-blockers.
Implications for Practice: The findings suggest that in patients with a history of myocardial infarction and stable cardiovascular health, continuing beta-blocker therapy is preferable to interruption. Discontinuation may increase the risk of adverse cardiovascular outcomes without offering quality of life benefits, supporting the ongoing use of beta-blockers in this population.
RCT: Hypothermic Oxygenated Perfusion Trends Toward Lower Primary Graft Dysfunction in Heart Transplantation – The Lancet
17 Aug, 2024 | 19:38h | UTCStudy Design and Population: This randomized, controlled, open-label, multicenter clinical trial evaluated the safety and efficacy of hypothermic oxygenated machine perfusion (HOPE) compared to static cold storage (SCS) in preserving donor hearts for transplantation. Conducted across 15 transplant centers in eight European countries, the study enrolled 229 adult heart transplant candidates between November 2020 and May 2023. The trial included 204 patients who received a transplant and met the study’s inclusion and exclusion criteria.
Main Findings: The primary composite endpoint, including cardiac-related death, graft dysfunction, and rejection within 30 days post-transplant, occurred in 19% of patients in the HOPE group compared to 30% in the SCS group, reflecting a 44% risk reduction (HR 0.56, 95% CI 0.32–0.99, p=0.059). Notably, primary graft dysfunction was significantly lower in the HOPE group (11% vs. 28%, RR 0.39, 95% CI 0.20–0.73). The incidence of major adverse cardiac transplant events was also reduced with HOPE (18% vs. 32%, RR 0.56, 95% CI 0.34–0.92).
Implications for Practice: HOPE showed a potential clinical benefit by reducing the incidence of primary graft dysfunction and major adverse cardiac events after heart transplantation. Although the primary endpoint was not statistically significant, the observed risk reductions suggest that HOPE could improve outcomes in heart transplantation. Further research is needed to confirm these findings and optimize donor heart preservation strategies.
2024 ACC Expert Consensus Decision Pathway on Clinical Assessment, Management, and Trajectory of Patients Hospitalized With Heart Failure – J Am Coll Cardiol
14 Aug, 2024 | 12:47h | UTCIntroduction: The American College of Cardiology (ACC) has released a focused update on the 2019 Expert Consensus Decision Pathway (ECDP) for the management of patients hospitalized with heart failure (HF). This update reflects new evidence and aligns with the latest ACC/AHA/HFSA heart failure guidelines.
Key Points:
1 – SGLT Inhibitors in Hospitalization:
– The update emphasizes the use of sodium-glucose cotransporter 2 (SGLT2) inhibitors during hospitalization for heart failure, regardless of left ventricular ejection fraction (LVEF). These medications should be initiated early, provided the patient is hemodynamically stable and there are no contraindications such as type 1 diabetes or severe kidney dysfunction.
2 – Triage and Admission Criteria:
– Patients with a new diagnosis of HF with rapidly progressing symptoms, severe congestion, or higher disease complexity should generally be admitted from the emergency department (ED). Some low-risk patients may be managed in an observation unit or via Hospital at Home (HaH) programs.
3 – Daily Trajectory Review:
– The clinical trajectory of hospitalized HF patients should be reviewed daily to monitor for effective decongestion and the need for initiation of guideline-directed neurohormonal therapies. Adjustments should be made based on patient response.
4 – Neurohormonal Therapy Optimization:
– Strategies for optimizing neurohormonal therapies, including beta-blockers, angiotensin receptor/neprilysin inhibitors (ARNIs)/angiotensin-converting enzyme (ACE) inhibitors/angiotensin receptor blockers (ARBs), and mineralocorticoid antagonists (MRAs), are updated. Therapy should be personalized based on patient tolerance, hemodynamics, and kidney function.
5 – Decongestion Strategies:
– The update provides enhanced guidance on diuretic therapy, including the use of dual nephron blockade and carbonic anhydrase inhibitors like acetazolamide for patients not responding adequately to loop diuretics.
6 – Palliative Care Integration:
– The role of palliative care has been highlighted, particularly for patients with worsening HF or those not responding to standard treatments. Early referral to palliative care can improve advance directive completion rates and reduce readmissions.
7 – Discharge and Follow-Up:
– Detailed discharge planning is crucial, including providing patients and caregivers with comprehensive information on medications, follow-up appointments, and the importance of adhering to the prescribed regimen. Telehealth may be utilized for post-discharge follow-up.
Conclusion: This focused update to the ACC ECDP provides essential guidance for the clinical management of patients hospitalized with heart failure. It emphasizes the early initiation of SGLT inhibitors, careful daily trajectory reviews, optimization of neurohormonal therapies, and the integration of palliative care. These updates aim to improve patient outcomes by addressing both short-term and long-term management strategies.
2024 AHA/ACC/AMSSM/HRS/PACES/SCMR Guideline for the Management of Hypertrophic Cardiomyopathy – J Am Coll Cardiol
11 May, 2024 | 14:20h | UTCIn a significant advancement for the treatment of hypertrophic cardiomyopathy (HCM), the American Heart Association and the American College of Cardiology, along with other leading societies, have released updated guidelines to optimize patient care. Here are the essential updates and recommendations for practicing physicians:
1 – Updated Diagnostic Strategies: The guideline emphasizes the use of advanced imaging techniques and genetic testing to enhance diagnostic accuracy, enabling personalized treatment approaches.
2 – Risk Assessment Tools: Revised tools for sudden cardiac death (SCD) risk assessment are detailed, aiding clinicians in making informed decisions regarding the use of implantable cardioverter-defibrillators (ICDs).
3 – Management of Obstructive HCM: New recommendations for the pharmacological treatment of symptomatic obstructive HCM include the use of disopyramide and advanced therapies such as septal reduction when initial medication does not suffice.
4 – Guidelines on Exercise and Lifestyle: The guidelines provide a nuanced approach to physical activity, recognizing the benefits while outlining the risks for patients with HCM. Detailed advice is offered on managing competitive sports involvement and other lifestyle considerations.
5 – Multidisciplinary Approach: The guidelines advocate for a team-based approach involving specialized HCM centers, ensuring patients benefit from comprehensive expertise and the latest treatment modalities.
6 – Innovations in Treatment: Highlighting new therapeutic options like myosin inhibitors, the guidelines underscore their role in managing obstructive symptoms when traditional medications are inadequate.
7 – Special Populations: Detailed sections on the management of HCM in children and pregnant women, addressing the unique challenges these groups face.
These guidelines represent a cornerstone in the evolving landscape of HCM management, embodying a commitment to enhancing outcomes and quality of life for patients through evidence-based practices and collaborative care.
Reference (link to free full-text):
RCT: Empagliflozin does not reduce heart failure hospitalization or death post-myocardial infarction
29 Apr, 2024 | 12:39h | UTCThis randomized, placebo-controlled trial assessed empagliflozin in preventing heart failure or death in patients recently hospitalized for acute myocardial infarction. Among 6,522 patients divided evenly into empagliflozin and placebo groups, there was no significant difference in the primary outcome—a composite of heart failure hospitalization or death—after 17.9 months. The empagliflozin group saw 8.2% experiencing the primary outcome versus 9.1% in the placebo group, yielding a non-significant hazard ratio of 0.90 (95% CI, 0.76 to 1.06; P=0.21). The results indicate that empagliflozin does not effectively reduce the risk of heart failure or mortality compared to placebo in this setting.
Reference (link to abstract – $ for full-text):
RCT: Semaglutide significantly improves symptoms and weight loss in HFpEF and type 2 diabetes patients
29 Apr, 2024 | 12:36h | UTCThis randomized clinical trial evaluated the effects of semaglutide on 616 patients with obesity-related heart failure with preserved ejection fraction (HFpEF) and type 2 diabetes. Patients received weekly doses of 2.4 mg semaglutide or a placebo for 52 weeks. The study’s primary findings included a significant improvement in heart failure–related symptoms, as measured by the Kansas City Cardiomyopathy Questionnaire clinical summary score (average increase of 13.7 points in the semaglutide group versus 6.4 points in the placebo group). Additionally, semaglutide treatment resulted in a mean 9.8% reduction in body weight compared to 3.4% with placebo. Secondary outcomes also favored semaglutide, showing enhancements in 6-minute walk distance and reductions in C-reactive protein levels. Notably, semaglutide was associated with fewer serious adverse events compared to placebo.
Reference (link to abstract – $ for full-text):
RCT: Efficacy and safety of microaxial flow pump in STEMI-related cardiogenic shock
28 Apr, 2024 | 20:17h | UTCThis randomized clinical trial assessed the impact of a microaxial flow pump (Impella CP) on mortality in 355 patients with ST-segment elevation myocardial infarction (STEMI) complicated by cardiogenic shock. Patients were randomly assigned to receive either the microaxial flow pump plus standard care or standard care alone. The primary outcome was mortality at 180 days. Results showed a significant reduction in death rates in the microaxial flow pump group (45.8%) compared to the standard care group (58.5%) with a hazard ratio of 0.74 (95% CI, 0.55 to 0.99; P=0.04). However, the incidence of severe adverse events was notably higher in the microaxial flow pump group, including severe bleeding and device-related complications.
Reference (link to abstract – $ for full-text):
Pooled Analysis: Semaglutide improves symptoms and reduces weight in obesity-related heart failure with preserved ejection fraction
28 Apr, 2024 | 16:33h | UTCThis pooled analysis of the STEP-HFpEF and STEP-HFpEF DM randomized trials assessed the efficacy of semaglutide in 1,145 participants with obesity-related heart failure and preserved ejection fraction, across 129 research sites globally. Participants, who had a BMI of at least 30 kg/m2 and varied cardiovascular conditions, were administered 2.4 mg of semaglutide weekly for 52 weeks. Semaglutide significantly improved heart failure-related symptoms (7.5 points increase in KCCQ-CSS), reduced body weight by 8.4%, and increased the 6-min walk distance by 17.1 meters, compared to placebo. The treatment also demonstrated safety, with fewer serious adverse events than the placebo group. These benefits were consistent across various subgroups, confirming semaglutide’s potential as a treatment in this patient population.
Reference (link to abstract – $ for full-text):
M-A: Cardiovascular benefits of SGLT2 inhibitors in patients without diabetes
22 Mar, 2024 | 11:07h | UTCStudy Design and Population: This meta-analysis investigated the cardiovascular (CV) outcomes associated with sodium-glucose cotransporter-2 inhibitors (SGLT2i) in patients without diabetes mellitus (DM). By systematically reviewing online databases, the authors identified and included six randomized controlled trials (RCTs) in their analysis. These trials compared SGLT2i with placebo/control in a total of 12,984 participants, who were followed for an average duration of 17.7 months. The study population comprised mainly patients with heart failure (HF), chronic kidney disease, or myocardial infarction, with a mean age of 64 years, where 72% were men and the mean hemoglobin A1C level was 5.7%.
Main Findings: The use of SGLT2i was associated with a significant reduction in composite CV death or hospitalization for HF, with an odds ratio (OR) of 0.77 (95% confidence interval [CI], 0.68 to 0.87, p < 0.0001), primarily due to a decrease in hospitalization for HF (OR 0.70, 95% CI 0.60 to 0.81, p < 0.00001). No significant differences were observed in CV death, all-cause death, or major adverse CV events when comparing SGLT2i to placebo. Notably, serious adverse events were lower with the use of empagliflozin compared to placebo.
Implications for Practice: This meta-analysis highlights the significant CV benefits of SGLT2i treatment in reducing CV death or hospitalization for HF in patients without DM, compared with placebo. These findings suggest the potential for broader use of SGLT2i in populations without diabetes to improve cardiovascular outcomes.
Reference: Sahib Singh et al. (2024). Cardiovascular Outcomes With Empagliflozin and Dapagliflozin in Patients Without Diabetes. The American Journal of Cardiology, Published: February 29, 2024. DOI: https://doi.org/10.1016/j.amjcard.2024.02.039. Access the study here: [Link]
Cohort Study | Younger age at hypertrophic cardiomyopathy diagnosis, male sex among predictors of developing LV systolic dysfunction
11 Aug, 2023 | 15:16h | UTC
Commentary on Twitter
@sarahaboualaiwi and colleagues provide new #clinicalresearch; Left Ventricular Systolic Dysfunction in #HCM diagnosed in childhood, Important insights into prevalence and prognosis from the SHaRe Registry #Circulation @sday_hcm @CSHeartResearch @tikuowens https://t.co/2TJ0XMe3B7 pic.twitter.com/o2mhcNjUfw
— Circulation (@CircAHA) June 2, 2023
Cohort Study | U-shaped relationship between BMI and mortality in heart failure patients
11 Aug, 2023 | 15:12h | UTCBody mass index and survival in people with heart failure – Heart
Commentary on Twitter
Body mass index and survival in people with heart failurehttps://t.co/W20GR5qjTM pic.twitter.com/s2nX2sBZj7
— Heart_BMJ (@Heart_BMJ) August 2, 2023
Review | Management of worsening heart failure with reduced ejection fraction
7 Aug, 2023 | 15:03h | UTC
Commentary on Twitter
How do you manage patients with worsening #HFrEF? This review by @SJGreene_md, @JavedButler1 and team provides the latest evidence-based guidance for the medical management of this high-risk population. https://t.co/REAqsrHDjI#JACC #CardioTwitter @ShelleyZieroth @DCRINews pic.twitter.com/rZYD25vCoG
— JACC Journals (@JACCJournals) August 5, 2023
Review | Cardiorenal syndrome in the hospital
7 Aug, 2023 | 14:36h | UTCCardiorenal Syndrome in the Hospital – Clinical Journal of the American Society of Nephrology
Commentary on Twitter
The cardiorenal syndrome refers to a group of complex, bidirectional pathophysiological pathways involving dysfunction in both the heart and kidney. This Review focuses on the cardiorenal syndrome encountered in the hospital setting https://t.co/f05vpOPzCx pic.twitter.com/4Is5A2F1km
— CJASN (@CJASN) July 31, 2023
Registry Analysis | Takotsubo syndrome outcomes influenced by trigger type and patient characteristics
3 Aug, 2023 | 13:14h | UTCCommentary: Takotsubo Trigger Type Matters, With Physical Shocks Linked to Worse Outcomes – TCTMD
Study | Left ventricular dysfunction in brain-dead heart donors – incidence, reversibility, and implications
31 Jul, 2023 | 14:09h | UTCLeft Ventricular Dysfunction Associated With Brain Death: Results From the Donor Heart Study – Circulation (free for a limited period)
Registry Analysis | Similar 1-year mortality rates post-TAVR in cardiogenic shock patients surviving 30-day mark
31 Jul, 2023 | 13:47h | UTC
Commentary on Twitter
Outcomes of transcatheter aortic valve replacement in patients with cardiogenic shock https://t.co/Ci1MIWVYuE @escardio #EHJ #ESCYoung @ehj_ed @rladeiraslopes pic.twitter.com/zwvFUT8lKt
— European Society of Cardiology Journals (@ESC_Journals) June 29, 2023