Top Cardiology Highlights from April 2025: Key Clinical Updates

April’s most-read cardiology news reflects the vibrancy and complexity of the field—drawing from major late-breaking trials, expert debates, and clinical pearls from the 2025 American College of Cardiology (ACC) Scientific Sessions in Chicago. This month’s top 10 spans topics from cerebral embolic protection in TAVI to the ongoing PCI vs. CABG debate, and fresh insights into managing ischemia with nonobstructive coronary arteries (INOCA).

Here’s what captivated clinicians this month:

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1. BHF PROTECT-TAVI Trial Dims Hope for Embolic Protection in TAVI

The British Heart Foundation-funded trial dealt another blow to cerebral embolic protection during transcatheter aortic valve implantation (TAVI). Despite expert disappointment, the door may not be fully closed yet on embolic filters.

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2. ACC WARRIOR Trial: No Clear Strategy Yet for INOCA

The trial focused on patients with ischemia with nonobstructive coronary arteries (INOCA), showing no reduction in cardiovascular events with intensive therapy. COVID-19 disruptions limited definitive conclusions.

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3. OPINION: The Cath Lab Attire Debate—Time to Update Dress Codes?

Discussion around sterile attire in the cath lab—like bouffant caps and beard covers—questions whether tradition is trumping evidence. Are the current infection-control measures overdone?

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4. RIVAWAR Trial: Rivaroxaban Stands Up to Warfarin for LV Thrombus Post-MI

In patients with left ventricular thrombus after myocardial infarction, rivaroxaban proved comparable to warfarin in efficacy and safety, offering clinicians a modern anticoagulation option.

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5. Final FAME 3 Results: PCI Matches CABG at 5 Years

Fractional flow reserve (FFR) and drug-eluting stents (DES) may have helped percutaneous coronary intervention (PCI) catch up with coronary artery bypass grafting (CABG) in multivessel disease patients.

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6. ACC SOUL: Oral Semaglutide Impresses in High-Risk Diabetes

The trial showed oral semaglutide outperformed standard care in high-risk type 2 diabetes patients. For those reluctant to use injectables, this could be a game changer.

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7. COMPARE-TAVI 1-Year Results: Myval Shows Strong Performance

The Myval valve stood its ground against industry leader Edwards Sapien in intermediate-risk TAVI patients. Room remains for new players in the growing TAVI space.

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8. Mavacamten Falls Short in Nonobstructive HCM Phase III Trial

Despite early hope, mavacamten didn’t improve outcomes in patients with nonobstructive hypertrophic cardiomyopathy (HCM). Experts now stress it’s a distinct entity from obstructive HCM.

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9. TRILUMINATE: TEER Lowers HF Hospitalizations at 2 Years

The tricuspid edge-to-edge repair (TEER) approach not only improved quality of life at 1 year, but also significantly cut heart failure hospitalizations by year 2.

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10. Evolut Low-Risk 5-Year Data: TAVI Keeps Pace with Surgery

The 5-year follow-up from the Evolut Low Risk Trial reaffirmed that TAVI remains a strong option, even among low-risk surgical candidates.

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Final Thoughts

April’s cardiology highlights underscore how rapidly practice evolves—both through rigorous clinical trials and the nuance of real-world experience. Whether you're a clinician, researcher, or student, staying informed on these trends is key to delivering the best care.

Lorundrostat Shows Promise for Treatment-Resistant Hypertension: Results from Advance-HTN Trial

Lorundrostat, a novel aldosterone synthase inhibitor, is emerging as a potent therapy for patients with treatment-resistant hypertension. In the phase IIb Advance-HTN trial, lorundrostat demonstrated significant blood pressure (BP) reduction in patients who were already on multiple antihypertensive medications.

Key Findings from the Advance-HTN Trial

• 15.4 mm Hg drop in 24-hour systolic BP after 12 weeks of treatment with 50 mg daily lorundrostat.

• Patients included in the study had persistent office BP readings ≥130/90 mm Hg despite two to five antihypertensive agents.

• Lorundrostat outperformed placebo significantly, with placebo-adjusted BP drops of:

  • −7.9 mm Hg in the stable-dose group

  • −6.5 mm Hg in the dose-adjustment group

• 41% of patients on lorundrostat achieved systolic BP <125 mm Hg at 4 weeks versus 18% with placebo.

• Drug efficacy was independent of BMI—a key advantage in diverse patient populations.

Study Design Enhancements

• A standardized 3-week run-in phase ensured patients had optimized background therapy.

• The trial used 24-hour ambulatory BP monitoring, a gold standard, rather than relying solely on clinic measurements.

• A large number of Black participants were included, a group with a higher incidence of primary aldosteronism, which lorundrostat specifically targets.

Safety Considerations

• Adverse events were consistent with RAAS (renin-angiotensin-aldosterone system) modulation:

  • Hyperkalemia (serum K⁺ > 6.0 mmol/L) in 5-7% of treated patients

  • Mild drops in eGFR and occurrences of hyponatremia

• Serious adverse events were few and manageable with close monitoring.

• Longer-term safety remains under investigation in ongoing phase III studies.

Why Lorundrostat May Be a Game-Changer

• Targets the root hormonal cause of hypertension—aldosterone excess.

• Offers a new mechanism compared to beta-blockers, calcium channel blockers, or diuretics.

• Could serve as an earlier-line option in patients with confirmed aldosterone-driven hypertension.

• Potential for broader use in conditions like heart failure or chronic kidney disease pending further research.

What’s Next?

• Awaiting phase III data for regulatory approval.

• Emphasis now lies on tolerability, long-term efficacy, and comparison with existing agents like spironolactone.

• If approved, lorundrostat could become a go-to add-on agent in challenging hypertension cases, particularly when aldosterone plays a central role.

Summary Points

• Lorundrostat lowers BP by blocking aldosterone synthesis at the adrenal level.

• Leads to less sodium reabsorption and fluid retention, reducing BP.

• May cause hyperkalemia, so electrolytes must be monitored.

• Ideal candidate for patients with resistant hypertension and suspected aldosterone excess.

VT Ablation Gains Ground with New VANISH2 Trial Evidence

Catheter ablation for ventricular tachycardia (VT) is increasingly proving to be a superior treatment compared to traditional medical management in patients with ischemic cardiomyopathy. The latest support comes from the VANISH2 trial, which adds significant weight to earlier research and is expected to influence upcoming clinical guidelines.

Why VANISH2 Matters

Ventricular arrhythmias, especially in those with prior heart damage, are life-threatening and contribute to:

• Sudden cardiac death

• ICD shocks that can cause trauma and anxiety

• Frequent hospitalizations

• Progressive heart failure

Traditionally managed with antiarrhythmic drugs, many of which have substantial side effects, catheter ablation is now being considered earlier in treatment thanks to trials like VANISH2.

What VANISH2 Found

The VANISH2 trial, released in late 2024, compared first-line catheter ablation versus antiarrhythmic medications in patients with:

• Ischemic cardiomyopathy

• Clinically significant VT

• An implanted ICD

Results showed catheter ablation significantly reduced the risk of death or serious arrhythmias.

Strengthened by Meta-Analysis

A meta-analysis that included 10 trials and 1,440 patients (29% from VANISH2) found:

Outcome	Relative Risk (RR)	Confidence Interval (CI)	Significance
Composite Primary Outcome	0.81	0.66–0.99	✅ Significant
ICD Shocks	0.68	0.53–0.88	✅ Significant
VT Storm	0.74	0.56–0.98	✅ Significant
Recurrent VT	0.85	0.73–0.98	✅ Significant
Hospitalization	0.82	0.68–0.98	✅ Significant
Mortality	0.91	0.72–1.14	❌ Not Significant

🔍 Key Insight: Ablation is effective in reducing arrhythmic burden but hasn’t shown a clear mortality benefit, possibly due to competing comorbidities.

Future of VT Management

• There’s growing support for ablation as first-line therapy, especially in patients who are ICD recipients.

• Current European guidelines recommend ablation after amiodarone failure; VANISH2 may push that recommendation earlier in the care pathway.

• Experts argue that early intervention might change patient outcomes dramatically and avoid prolonged exposure to toxic drugs.

Limitations to Consider

• Differences in trial designs, patient populations, and ablation techniques limit how broadly we can generalize.

• Meta-analyses can blur findings when trials are too heterogeneous.

Yet, the core message remains strong: Catheter ablation is a powerful, underused tool in managing VT. VANISH2 may mark the turning point in making ablation standard early care.

PRAETORIAN-XL Trial: Fewer Lead-Related Complications With Subcutaneous ICDs

 Key Highlights From the Study

• PRAETORIAN-XL, an extended follow-up of the original PRAETORIAN trial, compared subcutaneous ICDs (S-ICDs) with transvenous ICDs over a median follow-up of 7.3 years.

• Primary endpoint (all major and minor device-related complications) showed no significant difference: 8.0% (S-ICD) vs 11.6% (transvenous ICD).

• S-ICDs had significantly fewer:

• Major complications needing intervention: 5.7% vs 10.2%

• Lead-related complications: 2.4% vs 8.3%

📌 Key Concepts

• S-ICD eliminates the need for intracardiac leads, reducing risks like lead failures, infections, cardiac perforation, and tamponade.

• Most S-ICD complications occurred post-crossover to another device, often CRT-D, due to heart failure progression.

• Battery-related issues arose ~5–6 years post-implantation with first-generation S-ICDs.

🩺 Clinical Takeaways

• S-ICD is favored in younger patients without pacing needs, especially those at high risk for infection or with vascular anomalies.

• Transvenous ICDs remain simpler to implant (often under conscious sedation) and allow for future pacing, which may become necessary.

• Crossover rates: ~10–12% in both groups; often due to evolving heart failure requiring device upgrade.

🧠 Expert Opinion

• Electrophysiologists urge individualized decision-making, noting:

  • ICD technology continues to evolve.

  • No definitive winner—choice should depend on patient-specific risk factors.

🔍 Bottom Line

While S-ICDs reduce major and lead-related complications, they are not yet the universal choice. Tailoring ICD therapy to individual patient profiles remains the gold standard in modern electrophysiology.

Beyond Weight Loss: GLP-1 Agents in AF Secondary Prevention

GLP-1 receptor agonists may reduce atrial fibrillation (AF)-related events in patients with obesity and type 2 diabetes, according to the TRANSFORM-AF study.

The observed benefit was not fully explained by weight loss, suggesting pleiotropic effects beyond weight management.

Patients treated with GLP-1 drugs had a lower risk of hospitalization, cardioversion, ablation, or death compared to those on other diabetes medications.

Potential benefits appeared greater in patients with severe obesity (BMI > 40 kg/m²).

Weight loss differences between GLP-1 and other therapies were modest (14.1% vs 10.9%), reinforcing a metabolic mechanism beyond weight loss.

Use of GLP-1 agents could complement conventional AF management strategies like ablation and antiarrhythmic drugs.

Experts emphasized the need for randomized controlled trials (RCTs) but acknowledged ethical and practical challenges in designing them.

The findings shift attention toward targeting cardiometabolic risk factors (like obesity) in the secondary prevention of AF.

Although promising, the study limitations include its observational design, mostly male population, and potential for unmeasured confounders.

Future direction: Combining GLP-1 therapy with lifestyle modifications may represent a pivotal change in managing AF in obese and diabetic patients.

Meta-Analysis Highlights Potential Utility of CCT-FFR in Stable CAD Management

The clinical implications of CCT-derived fractional flow reserve (FFRct) in managing stable coronary artery disease (CAD) continue to be a subject of ongoing discussion. To further elucidate the potential benefits of incorporating this non-invasive modality into our diagnostic armamentarium, a meta-analysis was conducted comparing outcomes in patients with suspected stable CAD undergoing FFRct as a first-line strategy versus conventional non-urgent cardiovascular testing guided by clinical assessment.

This analysis encompassed five studies (three randomized controlled trials and two observational studies), representing a total of 5,282 patients. The studies compared two distinct diagnostic and management strategies:

• CCT-FFR as a first strategy: In this approach, patients initially underwent Coronary Computed Tomography Angiography (CCTA). CCTA is a non-invasive imaging technique that uses X-rays and contrast dye to visualize the coronary arteries. If CCTA revealed the presence of coronary artery stenosis (narrowing), further analysis was often performed to calculate the fractional flow reserve derived from CCTA (FFRct). FFRct is a computational technique that uses CCTA images to estimate how much a stenosis limiting blood flow to the heart muscle. This functional information helps determine the physiological significance of the stenosis. Management decisions, such as whether to pursue invasive coronary angiography or revascularization (e.g., PCI or CABG), were then guided by the CCTA and, when performed, the FFRct results.

• Non-urgent cardiovascular testing after a clinical judgment (Control Group): This strategy involved a more traditional approach to evaluating patients with suspected stable CAD. Patients underwent a clinical assessment, including a review of their symptoms, risk factors, and medical history. Based on this assessment, physicians selected appropriate non-invasive or invasive diagnostic tests. These tests could include:

  • Exercise stress testing: To evaluate heart function during physical exertion.

  • Nuclear stress testing (SPECT): To assess blood flow to the heart muscle.

  • Stress echocardiography: To assess heart function and wall motion during stress.

  • Invasive coronary angiography (ICA): A procedure in which a catheter is inserted into the coronary arteries to visualize them with X-rays.

The choice and sequence of these tests were determined by the physician's clinical judgment, following established guidelines.

Of the total patients, 2604 underwent CCT-FFR as the initial strategy, while 2678 patients comprised the control group, receiving standard clinical assessment and subsequent non-invasive or invasive testing as deemed appropriate. Quantitative synthesis of the data revealed the following key findings:

• Reduced Invasive Coronary Angiography (ICA) Rates: The CCT-FFR strategy was associated with a significant reduction in the overall rate of ICA (OR 1.57, 95% CI 1.36–1.81, p < 0.001).

• Lower Rates of Non-Obstructive CAD on ICA: Notably, the likelihood of undergoing ICA and demonstrating no obstructive CAD was substantially lower in the CCT-FFR group (OR 6.63, 95% CI 4.79–9.16, p < 0.001).

• Increased Rates of Coronary Revascularization: Conversely, patients in the CCT-FFR arm underwent coronary revascularization more frequently compared to the control group (OR 0.48, 95% CI 0.38–0.62, p < 0.001).

• Comparable 1-Year Major Adverse Cardiac Events (MACE): Despite the differential rates of subsequent procedures, there was no statistically significant difference in the incidence of 1-year MACE between the two strategies (OR 1.11, 95% CI 0.86–1.44, p = 0.42). Similarly, rates of nonfatal myocardial infarction (OR 0.73, 95% CI 0.41–1.33, p = 0.31), all-cause mortality (OR 1.29, 95% CI 0.47–3.54, p = 0.63), and unplanned revascularization for angina (OR 0.99, 95% CI 0.65–1.49, p = 0.95) were comparable between the groups.

Conclusion:

This meta-analysis suggests that in the management of stable CAD, an initial strategy incorporating CCT-FFR is associated with lower overall rates of ICA and a reduced likelihood of ICA demonstrating non-obstructive disease. Furthermore, this approach appears to facilitate higher rates of coronary revascularization. However, it is important to note that these differences did not translate into a statistically significant difference in 1-year clinical outcomes, as assessed by MACE.

These findings warrant careful consideration as we strive to optimize diagnostic pathways for patients with stable CAD. While CCT-FFR demonstrates potential for reducing unnecessary invasive procedures and potentially guiding more targeted revascularization, further investigation into its long-term clinical impact and cost-effectiveness is warranted.

Key Take-Home Points:

• CCT-FFR as an initial strategy in stable CAD management is associated with fewer overall ICAs.

• The use of CCT-FFR leads to a lower likelihood of ICAs revealing no significant blockages.

• CCT-FFR appears to result in higher rates of coronary revascularization.

• Despite these differences in procedures, 1-year rates of MACE, MI, mortality, and unplanned revascularization were similar between the CCT-FFR and standard care groups.

• While CCT-FFR shows promise in refining diagnostic pathways and potentially guiding treatment, its long-term clinical impact requires further study.