Key Points:

• REALIZE-K trial was a double-blind, placebo-controlled, randomized withdrawal study investigating SZC’s ability to maintain normokalemia (NK) and optimize spironolactone therapy (≥25 mg daily) in HFrEF patients with or at risk of HK.
• In participants with HFrEF and hyperkalemia, SZC led to large improvements in the percentage of participants with normokalemia while on optimal spironolactone dose, and reduced risk of hyperkalaemia and down-titration/discontinuation of spironolactone.
• Although underpowered for clinical outcomes, more participants had HF events with SZC than placebo, which should be factored into the clinical decision making.

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Key Points:

• AI-ECHO RCT is the first randomized trial to evaluate AI-based automated analysis within a real-world clinical echocardiography workflow.
• The study demonstrated:
  • Improved Workflow Efficiency: AI-assisted workflows increased the number of daily examinations per sonographer and reduced examination time.
  • Enhanced Data Analysis: The number of parameters analyzed per study tripled on AI-assisted days, showcasing comprehensive capabilities.
  • High Diagnostic Accuracy: Strong concordance between AI-generated data and expert-reviewed results, with parameters like LVEF showing robust correlation.
  • Superior Image Quality: Higher rates of “excellent” ratings for images on AI-assisted days.

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Key Points:

• BROOKLYN was a phase III trial that assessed the safety and effectiveness of obicetrapib as an adjunct to maximally tolerated lipid-modifying therapies, in patients with heterozygous familial hypercholesterolemia (HeFH).
• Obicetrapib reduced LDL-C levels by 36.3% at day 84, reaching 41.5% at day 365.
• Obicetrapib also demonstrated a 54.3% reduction in lipoprotein(a) levels, addressing a key cardiovascular risk factor.
• Adverse events were comparable between groups, with no significant differences in serious adverse events or cardiovascular deaths.
• Obicetrapib also improved non-HDL cholesterol and apolipoprotein B levels, enhancing lipid management.

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Key Points:

• Sustained Efficacy: Continued improvements in cardiac biomarkers, functional capacity, and symptom relief over extended treatment periods.
• Safety Profile: Consistent safety findings with no new concerns emerging during long term use.
• Reduced Hospitalizations: Fewer heart failure hospitalizations, highlighting its clinical impact.
• Mechanism of Action: Stabilizes transthyretin to prevent amyloid fibril formation, mitigating myocardial damage.

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Key Takeaways:

1. Black patients with peripheral artery disease (PAD) had significantly higher major amputation rates than White patients across all U.S. states (3.0% vs. 0.9%, p<0.001), with disparities varying widely by state and correlating strongly with the Social Vulnerability Index (rho 0.46, p<0.001).
2. Geographic and community-level factors, including socioeconomic vulnerabilities, play a critical role in driving racial disparities in PAD treatment, emphasizing the need for equitable healthcare access and interventions targeting high-risk communities.

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Key Points:

• The presence of mitral annular calcification (MAC) in prior studies of transcatheter aortic valve replacement (TAVR) has been associated with poor outcomes, but these studies used semiqualitative assessment, whereas quantitative assessment has generally not been analyzed
• The CT-derived MAC score is a quantitative assessment that can used in patients undergoing TAVR, but its clinical significance has not been assessed
• In this study, MAC scores of moderate or severe were associated with increased mortality risk, and involvement of the anterolateral trigone (one component of the score) was independently associated with adverse outcomes
• The CT-derived MAC score may be a useful quantitative assessment of risk in severe AS patients requiring TAVR

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Key Points:

• Cardiac rehabilitation (CR) is a guideline-directed multifaceted intervention that is shown to improve cardiovascular morbidity and mortality, but enrollment is low, especially among underrepresented groups, owing due to multiple patient-level and health-system-level factors
• The mTECH-Rehab trial tested implementation of an equity-focused digital health intervention to determine improvement in functional capacity among study participants
• This study evaluated the functional capacity of participants after 12 weeks using the 6-minute walk test (6MWT) as well as various secondary outcomes important in cardiovascular disease (CVD) prevention
• Though the study’s methodology has been presented previously, preliminary results are forthcoming as the study is ongoing

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Key Takeaways:

• Zerlasiran, a short interfering RNA (siRNA) targeting lipoprotein(a) (Lp(a)), was well tolerated and led to significant reductions in Lp(a) serum concentrations in both healthy participants and patients with stable atherosclerotic cardiovascular disease (ASCVD).
• A single dose of 600 mg of zerlasiran resulted in a maximal median reduction of Lp(a) by 99%, with 90% and 89% reductions sustained at 201 days for the 300 mg and 450 mg doses, respectively.
• The study found no serious adverse events, with mild to moderate injection site reactions being the most common side effect. Elevations in C-reactive protein were transient and resolved by day 7.

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Key Takeaways:

• The AMULET IDE trial compared the AMPLATZER Amulet occluder with the Watchman 2.5 device in patients with nonvalvular atrial fibrillation (NVAF) at high risk of thromboembolism.
• Patients with the Amulet occluder were significantly more likely to be free from oral anticoagulation (OAC) at 5 years compared with the Watchman device (94.0% vs. 90.9%, p = 0.009) and clinical outcomes, including rates of ischemic stroke or systemic embolism (7.4% vs. 7.1%, p = 0.851) and major bleeding (20.1% vs. 20.0%, p = 0.882), were similar between the devices.
• Strokes in the Amulet occluder group were less often fatal or disabling compared to the Watchman group (22 vs. 39 events, p = 0.030).

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Key Takeaways:

1. In this international registry, 266 patients with dual pathology, aortic stenosis and cardiac amyloidosis were identified and matched.  A control cohort of lone AS receiving aortic valve replacement was used for outcome comparison.
2. ATTR-specific medication, predominantly tafamidis, significantly improved survival in patients with dual aortic stenosis (AS) and transthyretin-associated cardiac amyloidosis (ATTR-CA) (adjusted HR 0.42; 95% CI 0.24–0.72), emphasizing its role in managing this complex pathology.
3. Aortic valve replacement (AVR), particularly in severe AS, provided substantial survival benefits (HR 0.42; 95% CI 0.25–0.72), with the combination of AVR and ATTR-specific therapy yielding outcomes comparable to lone AS patients undergoing AVR.

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Key Points:

• Patients with peripheral artery disease (PAD) at an increased risk of both major adverse cardiovascular events (MACEs) and major adverse limb events (MALEs)
• Bempedoic acid is thought to reduce MACEs in primary and secondary prevention patients, but it is unknown whether the same can be said for MALEs
• The CLEAR Outcomes trial randomized patients to either bempedoic acid versus placebo to determine rates of MALEs, and some rates of MACEs, among at risk patients and patients diagnosed with PAD
• The study showed significant reduction in MALEs for all patients and patients with diagnosed PAD, as well as reduction in composite MACEs and MALEs, suggesting a possible role for bempedoic acid in PAD treatment and prevention

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KEY POINTS:

• Historically women have been underrepresented in cardiovascular clinical trials, however, rates of Heart Failure with Preserved Ejection Fraction are rising more rapidly in women
• FINEARTS-HF trial enrolled 46% of female participants and demonstrated a reduction in heart failure exacerbations in both sexes with the use of finerenone, compared to placebo

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Key Takeaways:

1. KRAKEN was an international, multicenter, placebo controlled, phase 2 trial that tested the effects of muvalaplin at different doses—10 mg, 60 mg or 240 mg, taken daily—vs placebo for 12 weeks.
2. Muvalaplin reduced Lp(a) levels by up to 85.8% at the highest dose (240 mg/day), with 96.7% of participants in this group achieving Lp(a) levels below 125 nmol/L.
3. The safety profile of muvalaplin was favorable, with mild to moderate gastrointestinal events being the most common side effects and no significant concerns regarding liver function or systemic inflammation markers.
4. Muvalaplin represents a significant advancement in addressing elevated Lp(a) levels, offering a potential oral treatment option that could reduce cardiovascular risk in individuals with high Lp(a) concentrations.

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Key Takeaways:

• The ONCO PE trial demonstrated that an 18-month treatment with rivaroxaban significantly reduced recurrent venous thromboembolism (VTE) compared to a 6-month treatment in patients with cancer and acute low-risk pulmonary embolism (PE) (5.6% vs. 19.1%; OR, 0.25; 95% CI, 0.09–0.72; P=0.01).
• There was no statistically significant increase in major bleeding events with the longer rivaroxaban treatment (7.8% vs. 5.6%; OR, 1.43; 95% CI, 0.44–4.70; P=0.55).
• The study highlights the benefits of extended anticoagulation in preventing thrombotic events in this patient population, though individual bleeding risks must be considered.

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Key Points:

• Anthracycline (ANT)-based chemotherapy is a known cancer treatment regimen but results in cardiotoxicity secondary to heart failure
• The SARAH trial explored whether the angiotensin receptor-neprilysin inhibitor (ARNi), sacubitril/valsartan, might be cardioprotective against heart failure among high-risk patients receiving ANT therapy
• The study investigated treatment with ARNI versus placebo for 6 months to determine the incidence of worsened global longitudinal strain (GLS) in the left ventricle (LV) as well as other secondary outcomes
• The SARAH trial found lower rates of worsened GLS as well as improved GLS in the ARNi group compared to the control group, raising questions about the benefits of ARNi for prevention of cardiotoxicity in high-risk patients

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Key Takeaways:

1. In this secondary analysis of the SELECT Trial, semaglutide 2.4 mg once weekly significantly reduced the risk of major adverse cardiovascular events (MACE) in patients with or without a history of coronary artery bypass grafting (CABG), with a greater absolute risk reduction observed in the CABG group (2.3% vs. 1.0%).
2. Patients with prior CABG, who were at higher baseline cardiovascular risk, experienced fewer serious adverse events with semaglutide (38%) compared to placebo (44%), reinforcing its efficacy and safety in this high-risk subgroup.

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Key Points:

• In patients with treatment-refractory symptomatic obstructive hypertrophic cardiomyopathy (HCM), invasive septal reduction therapies (SRT)—alcohol septal ablation or surgical myectomy—are often the last resort for symptom management. Septal reduction therapies are limited in availability and associated with procedural risks.
• The VALOR-HCM trial demonstrated that mavacamten significantly reduced the need for SRT in severely symptomatic HCM patients at 16, 32, and 56 weeks.
• At 128 weeks, mavacamten provided sustained freedom from SRT, with nearly 90% of patients remaining on long-term therapy.

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Key Points

• Both chronic kidney disease (CKD) and cardiovascular disease (CVD) are prevalent in type 2 diabetes (T2DM), contributing to morbidity and mortality.
• The FLOW trial demonstrated that semaglutide, a GLP-1 receptor agonist, was associated with a 24% relative risk reduction in the primary composite kidney outcome compared to placebo among those with T2DM.
• This analysis stratified by baseline CVD status and CVD risk, and found consistent renal benefits across these subgroups without evidence of a heterogeneous treatment effect.

CKD and CVD  are leading causes of death and disability in patients with T2DM. Both conditions often coexist, increasing the risk of adverse outcomes. Semaglutide, a glucagon-like peptide-1 (GLP-1) receptor agonist, has shown promise in improving glycemic control and reducing the risk of CV events, but its effects on CKD outcomes, particularly in subgroups defined by CVD risk, are less well understood.

On November 18^th  2024, findings from “Benefits of Semaglutide on Chronic Kidney Disease Outcomes by Cardiovascular Status or Risk in the FLOW trial” were presented at AHA Scientific Sessions 2024.

The FLOW trial was a phase 3, double-blind, randomized controlled study designed to assess the effects of semaglutide on CKD progression in patients with type 2 diabetes. The study included 3,533 participants with type 2 diabetes and CKD, who were randomized to receive weekly subcutaneous semaglutide 1.0 mg or placebo. Participants met one of two inclusion criteria: eGFR 50–75 mL/min/1.73 m² with a urine albumin creatinine ratio (UACR) >300 to <5,000 mg/g, or eGFR 25–<50 mL/min/1.73 m² with a UACR >100 to <5,000 mg/g. Patients were followed for a median of 3.4 years. The trial’s primary endpoint was a composite of kidney failure (eGFR <15 mL/min/1.73 m², dialysis, or transplant), ≥50% eGFR decline from baseline, and kidney or CV death. This pre-specified subgroup analyses  stratified the participants by prior cardiovascular events or  CVD risk, including myocardial infarction (MI), stroke, peripheral artery disease (PAD) in those with baseline CVD, and CVD risk estimated using the PREVENT score in those without baseline CVD (categorized into <20% or ≥ 20%).

At baseline, participants had a mean age of 67 years, 30% were female, mean eGFR was 47 mL/min/1.73 m², and median UACR was 568 mg/g. In the overall population, semaglutide reduced the relative risk of the composite kidney outcome by 24% compared to placebo (HR: 0.76; 95% CI: 0.66–0.88). Annual eGFR decline was also slower with semaglutide. Benefits were consistent across all CVD and CV risk subgroups. Among those with prior MI, stroke, or PAD, hazard ratios ranged from 0.72 to 0.95, showing no significant heterogeneity. Patients with higher baseline CV risk (PREVENT score ≥20%) experienced similar reductions in kidney outcomes (HR: 0.73; 95% CI: 0.58–0.91) compared to those with lower risk scores (HR: 0.73; 95% CI: 0.49–1.08).

These FLOW trial results demonstrate that semaglutide provides substantial benefits in slowing CKD progression and reducing kidney failure in type 2 diabetes, regardless of cardiovascular status or risk. The findings underscore the broad applicability of semaglutide in managing the dual burden of diabetes and CKD.

Key Points:

• Many patients in low- and middle-Income countries are unable to obtain new pacemaker devices. It is unknown if reconditioned pacemakers are as effective as new pacemakers.
• In this randomized clinical trial, 298 patients who had class I indications for a pacemaker but no financial means to obtain one were given either a reconditioned pacemaker or a new pacemaker at implant.
• Reconditioned pacemakers was found to be non-inferior to new pacemakers for infection and lead complications at 90 days.

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Key Points:

• It is unknown if linear ablation with ethanol infusion of the vein of Marshall (EIVOM) in addition to pulmonary vein isolation (PVI) improves outcomes as compared to PVI alone in patients with persistent atrial fibrillation.
• In this investigator-initiated, open-label randomized clinical trial, 498 patients with persistent atrial fibrillation without a history of ablation were randomized in a 1:1 fashion.
• Linear ablation with EIVOM plus PVI was associated with freedom from atrial arrhythmia recurrence at 12 months compared to PVI alone.

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