FDA Approves Tendyne TMVR System for High-Risk Patients with Complex Mitral Valve Disease

Introduction

In a major regulatory milestone, the US Food and Drug Administration (FDA) has approved Tendyne, a transcatheter mitral valve replacement (TMVR) system developed by Abbott, for use in a carefully selected subset of high-risk patients with mitral valve disease. This landmark approval addresses a longstanding therapeutic gap for patients who are unsuitable for surgery and have anatomies unfavorable for transcatheter edge-to-edge repair (TEER).

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Tendyne: A New Option for a Difficult Population

The Tendyne system is now FDA-approved for patients with:

• Moderate-to-severe mitral regurgitation (MR)

• Severe mitral stenosis

• Moderate MR with moderate-or-greater mitral stenosis due to mitral annular calcification (MAC)

Importantly, these patients must be ineligible for surgery and have anatomy not suitable for TEER—a profile that has previously left clinicians with limited options.

The approval is supported by data from the SUMMIT trial, which evaluated outcomes in patients either randomized to Tendyne or to MitraClip-based TEER. The trial cohort notably included patients with extensive MAC, a calcific burden that renders traditional surgical and transcatheter repair approaches highly risky or technically infeasible.

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Why This Matters: The Clinical Challenge of MAC

Mitral annular calcification (MAC) significantly compromises the flexibility and function of the mitral annulus, leading to a complex spectrum of MR, stenosis, or mixed pathology. Patients with MAC are frequently elderly with multiple comorbidities, making them poor surgical candidates. As Dr. Paul Sorajja noted in the Abbott press release, “Many are considered too high risk for open-heart surgery.”

Until now, these patients had limited access to definitive therapy. TEER, while beneficial in many cases, requires favorable anatomy—something MAC often precludes due to leaflet rigidity and calcific extension.

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Guidelines: Bridging the Gap Between Evidence and Practice

• European Guidelines (ESC/EACTS 2021):

  • Primary MR: Surgical repair is the gold standard unless risk is prohibitive (Class I, Level B).

  • TEER: Considered for inoperable patients with suitable anatomy (Class IIb, Level B).

  • TMVR: May be considered in exceptional cases when neither surgery nor TEER is possible (Class IIb, Level C).

• US Guidelines (ACC/AHA 2020):

  • TEER: Reasonable for high/prohibitive risk patients with primary MR (Class IIa, Level B).

  • For secondary MR, TEER also has a Class IIa, Level B recommendation in selected symptomatic patients.

  • TMVR: Until now, it lacked formal guidance due to the absence of FDA approval.

With this new approval, Tendyne may soon be incorporated into future updates of the US guidelines, offering a lifesaving pathway for patients once considered beyond the reach of effective therapy.

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Global Context: Europe Leading the Way

Europe approved Tendyne five years earlier, based on the Tendyne Global Feasibility Study, allowing for real-world experience to accumulate in complex patients. The US approval will now enable similar progress domestically, offering physicians an expanded interventional toolkit.

Obicetrapib: A Promising CETP Inhibitor for LDL and Lp(a) Reduction

Introduction

Obicetrapib, a cholesteryl ester transfer protein (CETP) inhibitor developed by NewAmsterdam Pharma, has emerged as a promising lipid-lowering therapy. Unlike previous CETP inhibitors like anacetrapib, evacetrapib, torcetrapib, and dalcetrapib, which failed due to safety concerns, obicetrapib has shown impressive results in the BROADWAY and TANDEM trials. These studies, presented at the 2025 European Atherosclerosis Society Congress and published in the New England Journal of Medicine and The Lancet, highlight the potential of obicetrapib as a novel oral agent for managing low-density lipoprotein (LDL) and lipoprotein(a) [Lp(a)] in high-risk patients.

Background on CETP Inhibitors
CETP inhibitors have long been explored as a therapeutic option for cardiovascular disease, initially aiming to raise high-density lipoprotein (HDL) levels. However, this approach fell out of favor as studies like the ILLUMINATE trial demonstrated increased cardiovascular events and mortality with torcetrapib. The failure of earlier CETP inhibitors shifted the focus toward LDL reduction, which has proven to be a more effective strategy for reducing major adverse cardiovascular events (MACE).

BROADWAY Trial Findings
The BROADWAY trial enrolled 2,530 patients with heterozygous familial hypercholesterolemia (FH) or atherosclerotic cardiovascular disease (ASCVD) who were already on maximally tolerated lipid-lowering therapy. Key results include:

• LDL Reduction: A 29.9% reduction in LDL at day 84 versus a 2.7% increase in the placebo group (P < 0.001). This effect was maintained through 1 year.

• Lp(a) Reduction: A 33.5% reduction in Lp(a) levels, highlighting its potential as a dual-action lipid-lowering therapy.

• Adverse Events: Comparable overall adverse event rates between obicetrapib (59.7%) and placebo (60.8%), with low rates of liver-enzyme (0.6%) and muscle enzyme (0.3%) abnormalities.

TANDEM Trial Findings
The TANDEM trial further tested obicetrapib in 407 patients with heterozygous FH or ASCVD, including those at high risk but not on statins. Key results include:

• Combination Therapy: Fixed-dose combination with ezetimibe achieved a 48.6% LDL reduction compared to placebo, a 27.9% reduction compared to ezetimibe monotherapy, and a 16.8% reduction compared to obicetrapib monotherapy.

• Adverse Events: Low rates of serious adverse events (3-7%) across all study arms, reinforcing the safety profile seen in BROADWAY.

Clinical Implications and Future Directions
The promising results from the BROADWAY and TANDEM trials position obicetrapib as a potentially important addition to the lipid-lowering toolkit. The PREVAIL study, expected to report outcomes in 2026, will be crucial for determining the long-term cardiovascular benefits of this agent. If successful, obicetrapib could fill a critical gap for patients with elevated LDL and Lp(a) levels who may not qualify for existing injectable therapies.

Key Takeaways

• Obicetrapib offers significant reductions in both LDL and Lp(a), addressing a critical need in lipid management.

• Safety profile appears favorable, with low rates of serious adverse events.

• The upcoming PREVAIL trial will provide crucial long-term efficacy data.

Conclusion
Obicetrapib represents a promising step forward in lipid management, potentially providing clinicians and patients with a novel oral option for comprehensive cholesterol control. With further validation, it could become a mainstay in the management of ASCVD and heterozygous FH.

Benefits of SGLT2 Inhibitors for Heart Failure: Real-World Evidence from a Large French Cohort Study

 Introduction

Heart failure (HF) remains a leading cause of morbidity and mortality worldwide, imposing a significant burden on healthcare systems and affecting millions of patients. In recent years, sodium-glucose cotransporter 2 (SGLT2) inhibitors have emerged as a cornerstone in the treatment of HF, offering benefits beyond their original use in type 2 diabetes management. A recent, large-scale, real-world study conducted in France provides robust evidence supporting the efficacy of SGLT2 inhibitors in improving outcomes for heart failure patients, reinforcing the urgency of early initiation in clinical practice.

Study Overview and Key Findings
The study, published in the May 2025 issue of JACC: Heart Failure, analyzed data from the French National Health Data System, which covers more than 99% of the population. The study included 191,357 adults with a recent HF hospitalization between 2021 and 2023, excluding those with prior exposure to SGLT2 inhibitors or early mortality/readmission within 30 days of discharge. Key findings include:

• Reduced All-Cause Mortality and HF Hospitalization: Patients who initiated SGLT2 inhibitors had a significantly lower risk of all-cause death or HF hospitalization (HR 0.71; 95% CI 0.67-0.75).

• Rapid and Sustained Benefits: Benefits were evident as early as 18 days after initiation, with continued advantage over a mean follow-up of 9 months.

• Consistent Efficacy Across Subgroups: The effects were consistent regardless of age, sex, diabetes status, LVEF, or type of SGLT2 inhibitor used.

• Increased Uptake Over Time: SGLT2 inhibitor use within 30 days of discharge increased from 5.1% in 2021 to 35.0% in 2023, highlighting growing clinical acceptance.

• Early Initiation is Critical: Patients initiating treatment had a lower median age (76 vs 84 years), were more likely to be male (61.5% vs 45.7%), and had more frequent comorbidities like diabetes and reduced LVEF.

Clinical Implications and Urgency
The findings underscore the critical need to initiate guideline-directed medical therapy (GDMT) early in the management of HF. Delays in SGLT2 inhibitor initiation expose patients to unnecessary clinical risks, as highlighted by Stephen Greene, MD (Duke Clinical Research Institute). The rapid benefits observed in this study further reinforce the need for aggressive, proactive HF management, comparable to the urgency seen in oncology care.

Key Takeaways for Clinicians

1. Early Initiation Saves Lives: SGLT2 inhibitors reduce all-cause mortality and HF hospitalization risk significantly.

2. Rapid Impact: Benefits can emerge within days, reinforcing the need for prompt therapy.

3. Broad Patient Benefit: Efficacy is consistent across diverse patient groups, including those with advanced age and multiple comorbidities.

4. Rising Uptake: Increased use reflects growing awareness, but gaps remain in real-world practice.

5. Urgency in HF Management: Treat HF with the same urgency as other life-threatening conditions.

Early Cardiogenic Shock: Underrecognized and Often Undertreated

 Introduction 

Early cardiogenic shock (CS) remains a significant clinical challenge, often leading to poor outcomes if not identified and managed promptly. Despite its severe implications, it is frequently underrecognized, with only one in four patients having any electronic medical record (EMR) documentation indicating their shock status. These findings were highlighted in a multicenter study presented at the Society for Cardiovascular Angiography and Interventions (SCAI) 2025 Scientific Sessions in Washington, DC. This article summarizes the critical insights from this study and their implications for clinical practice.

SCAI SHOCK Classification and Study Design The SCAI SHOCK classification system, widely adopted for staging cardiogenic shock, includes five stages:

• A (At Risk) – Patients with a potential risk of shock

• B (Beginning) – Patients with isolated hypotension or hypoperfusion

• C (Classic) – Patients with clear evidence of shock

• D (Deteriorating) – Patients with worsening shock

• E (Extremis) – Patients in severe, life-threatening shock

The study included 500 patients admitted to six hospitals within the Brown University Health System between 2017 and 2022. It specifically focused on patients in SCAI Stage B shock, characterized by isolated hypotension or hypoperfusion.

Key Findings: Poor Outcomes in Early Shock Patients in Stage B shock had concerning outcomes, with approximately 25% requiring transfer to a higher level of care, deteriorating to a more severe shock stage, or dying during hospitalization. The median time to this primary endpoint was 16 hours. Importantly, those with poorer outcomes had a median duration of 11 hours in SCAI B shock compared to 5 hours in those with favorable outcomes, defined as survival without shock stage escalation or transfer for higher care.

Predictors of Poor Outcome Several factors were identified as predictors of poor outcomes in SCAI B shock:

• Acute Kidney Injury (AKI) – Strongly correlated with poor outcomes, particularly when present in more advanced stages.

• Diuretic Resistance – Indicated a failing cardiorenal response.

• Oliguria – Decreased urine output in the prior 24 hours was a significant warning sign.

In-hospital mortality rates were notably higher among those with hypotension (15.4%) compared to those with hypoperfusion (9.5%). Deterioration to a higher shock class occurred in 36.3% of those with hypotension, versus 11.8% with hypoperfusion.

Importance of Early Detection and Response The study's lead author emphasized the need for enhanced education across disciplines, including emergency department staff and emergency medical services (EMS), to recognize early cardiogenic shock. Dr. Vallabhajosyula also suggested that smart EMR-based detection tools, similar to those used for sepsis, could significantly improve early recognition and intervention.

Future Directions Improving early detection and documentation of SCAI Stage B shock should be a research priority. Additionally, better understanding the cardiorenal implications of early cardiogenic shock could guide more effective management strategies.

Key Takeaways for Clinicians

• Early Identification is Critical: Recognizing Stage B shock early can significantly alter patient outcomes.

• Monitor for Key Predictors: Watch for AKI, diuretic resistance, and oliguria as critical early indicators of poor prognosis.

• Implement Detection Tools: Consider integrating EMR sniffers to improve early shock recognition.

• Cross-Disciplinary Training Needed: Educate ED and EMS personnel to enhance early shock detection.

Conclusion Early cardiogenic shock presents a high-risk scenario, even in patients with isolated hypotension or hypoperfusion. Proactive detection and timely intervention are essential to improve outcomes, highlighting the need for system-wide awareness and advanced predictive tools.

Pulsed-Field Ablation for Atrial Fibrillation: Promising, But Not Without Risk

 Introduction

Pulsed-field ablation (PFA) has rapidly emerged as a novel technique for the treatment of atrial fibrillation (AF), offering the potential for tissue-specific ablation with fewer catastrophic complications than traditional thermal methods. However, new data presented at Heart Rhythm 2025 raises concerns about subclinical injury, cerebral embolism, and coronary complications, challenging the narrative that PFA is the “perfect” solution. As the electrophysiology (EP) community embraces this innovation, a deeper understanding of its safety profile is critical.

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Safety Signals from the NEMESIS-PFA Registry

The NEMESIS-PFA registry (n=871) compared PFA to radiofrequency ablation (RFA) and identified significantly greater increases in biomarkers of myocardial injury, hemolysis, and renal stress in PFA-treated patients.

• Cardiac biomarkers like troponin rose substantially higher post-PFA (median: 13,551 vs 128 ng/dL).

• Indicators of hemolysis—including LDH, haptoglobin, and free hemoglobin—also rose, suggesting red blood cell destruction.

• Creatinine levels increased more in the PFA group, raising concerns about acute kidney injury.

• Left atrial ejection fraction (LAEF) dropped more sharply (20% vs 5%), indicating transient atrial dysfunction.

These findings suggest that although PFA avoids esophageal and phrenic nerve injury, it may induce other systemic effects with unclear long-term significance. The biophysical characteristics of PFA catheters—such as electrode geometry, pulse parameters, and electric field strength—likely influence these effects.

🔗 NEMESIS-PFA registry results in JACC: Clinical Electrophysiology

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Asymptomatic Cerebral Emboli (ACE): PEACE-AF Findings

In the PEACE-AF study, brain MRI within 72 hours post-PFA revealed asymptomatic cerebral emboli (ACE) in 34% of patients.

• Older age and persistent AF were associated with increased ACE risk.

• No clinical stroke or TIA occurred, but long-term neurological outcomes are pending.

While ACE is not unique to PFA, its incidence and potential cognitive implications merit further investigation and systematic surveillance in future trials.

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Coronary Complications: Mild but Present

A third study assessed PFA near coronary arteries during cavotricuspid isthmus (CTI) or mitral isthmus ablation. Despite using intracoronary nitroglycerin, 47% of patients developed severe coronary spasm (>70% narrowing).

• OCT at 3 months showed luminal narrowing and vascular wall thickening, indicating mild coronary stenosis.

• No patients developed angina or required revascularization, but the data signal a need for vigilance, especially in catheter-specific contexts.

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PFA: Still an Evolutionary Technology

Despite these findings, PFA maintains several clear advantages:

• It avoids atrioesophageal fistula, a rare but often fatal complication of thermal ablation.

• It is faster, reducing procedure and left atrial dwell time.

• Some data suggest superior efficacy for rhythm control in select populations.

Ongoing device innovations include dual-mode catheters (e.g., Medtronic’s Sphere-9, capable of both PFA and RFA), which may allow tailored energy delivery based on anatomy and risk.

🔗 Medtronic Sphere-9 and Affera system

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Expert Perspectives: Caution Over Hype

Experts agree that PFA is a step forward, but not the panacea it's sometimes marketed to be:

• “We’ve traded one set of major problems for another set of possibly less dire but still significant issues,” said electrophysiologist Dhanunjaya Lakkireddy.

• “All EPs should understand that PFA is not universally safe, and safety varies by system design,” said Wilber Su.

• A special issue of Pacing and Clinical Electrophysiology on PFA fundamentals is expected to help standardize operator understanding.

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Key Takeaways for Clinicians

• PFA reduces catastrophic risks like atrioesophageal fistula, but introduces concerns related to myocardial injury, hemolysis, renal dysfunction, and cerebral emboli.

• Biomarker elevations and drop in atrial function post-PFA highlight a need for longitudinal safety surveillance.

• ACE incidence post-PFA (34%) supports MRI-based follow-up and neurological assessments in trials.

• Coronary spasm and stenosis may occur with PFA applied near coronary vasculature, warranting caution in such regions.

• Future catheter designs should allow selective energy delivery to balance safety and efficacy in different anatomical zones.

EARLY TAVR Trial Confirms Benefit of Early Aortic Valve Intervention Across All Age Groups

Introduction

In a paradigm-shifting update for cardiologists managing severe aortic stenosis (AS), new data from the EARLY TAVR trial reveal that patients, regardless of age—derive significant benefit from early transcatheter aortic valve implantation (TAVI) even before symptoms emerge. These findings, presented at SCAI 2025, come on the heels of FDA approval for the Sapien 3 valve for asymptomatic severe AS, signaling a strong shift toward proactive intervention over watchful waiting.

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The Case for Early TAVI: A Progressive, Unpredictable Disease

Severe AS has long been recognized as a progressive and potentially deadly disease, even when asymptomatic. The EARLY TAVR trial confirms that early intervention with TAVI reduces the composite risk of death, stroke, or unplanned cardiovascular hospitalization, compared with clinical surveillance.

“You want to do the procedure electively when the patient is stable,” said investigators, emphasizing the importance of planning ahead and initiating shared decision-making.

Source: NEJM
 

Key Findings Across Age Groups

The trial stratified patients into four age groups: 65–69, 70–74, 75–79, and 80+. The primary outcome consistently favored TAVI across all age brackets:

• 65–69 years:
  Dramatic reduction in death, stroke, or HF hospitalization:
  TAVI 4.7% vs Surveillance 25.6% (P = 0.016)
  Stroke rates: 0% with TAVI vs 13% with surveillance

• 80+ years:
  Stroke: 4.2% with TAVI vs 16.5% with surveillance
  HF hospitalization: 8.7% vs 19.4% (P = 0.008)

• 70–74 years:
  HF hospitalization reduced: 0.8% with TAVI vs 9.2% (P = 0.005)

Despite differences in comorbidity burden across age groups, the benefit of early TAVI persisted. Conversion to AVR in the surveillance group occurred at similar rates regardless of age, and importantly, 25% of strokes occurred during the wait period before delayed AVR.

Practical Implications for Clinicians

• Get dental clearance early to avoid procedural delays.

• Start shared decision-making discussions during the asymptomatic stage.

• Recognize early symptoms may be underestimated, as up to 20% of “asymptomatic” patients had guideline-based indications for AVR after workup.

• Consider subclinical cardiac damage and valve calcification progression when delaying treatment.

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Edwards Lifesciences' FDA-approved Sapien 3 TAVI platform for asymptomatic severe AS
Image source

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Key Takeaways for Busy Clinicians

• Early TAVI outperforms surveillance in asymptomatic severe AS, regardless of age.

• Major endpoints—death, stroke, HF hospitalization—are reduced with TAVI.

• Benefits are particularly striking in younger (65–69) and older (80+) patients.

• Up to 25% of strokes occurred during the watchful waiting period.

• Clinicians should begin planning early with thorough workups and shared decision-making.

TAVI in Women: Patient-Prosthesis Mismatch Doesn’t Impact Long-Term Survival

Introduction
As transcatheter aortic valve implantation (TAVI) expands into younger and lower-risk populations, patient-prosthesis mismatch (PPM) remains a hot topic—particularly in women with smaller annuli. A new multicenter analysis presented at the SCAI 2025 Scientific Sessions offers a reassuring message: while women are more likely than men to develop PPM after TAVI, this does not translate into worse long-term survival.

This finding challenges traditional assumptions about PPM and underscores the need for nuanced, patient-centered valve selection—especially for female patients.

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Understanding PPM in the Context of TAVI
PPM occurs when the effective orifice area of the prosthetic valve is too small relative to the patient’s body size, potentially leading to higher gradients and adverse outcomes. While this is a known concern in surgical aortic valve replacement (SAVR), its implications in the TAVI era are more complex.

Key insights include:

• Women had higher rates of predicted and echocardiographically measured severe PPM than men:

  • Predicted severe PPM: 1.7% (women) vs. 0.1% (men)

  • Measured severe PPM: 7.3% (women) vs. 5.4% (men)

• Despite this, 5-year survival was unaffected by PPM severity in women.

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Study Details
A total of 3,016 TAVI patients (44% women, mean age 80) treated across six hospitals within the Baylor Scott & White Healthcare System (2012–2021) were retrospectively analyzed:

• Balloon-expandable valves (Edwards Sapien series) were used in 74% of patients.

• Women were more likely to experience moderate or severe PPM, especially with balloon-expandable devices.

Despite theoretical concerns, measured or predicted PPM had no significant impact on 5-year survival—even among women with higher mismatch rates.

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The Valve Type Question: Self-Expanding vs Balloon-Expandable
Interestingly, moderate PPM was more frequent with balloon-expandable valves:

• Predicted moderate PPM: 31.3% (balloon-expandable) vs. 8.2% (self-expanding)

• Measured moderate PPM: 22.9% vs. 11%, respectively

Yet, a slight survival trend was noted:

• Women with self-expanding valves and moderate PPM showed a lower unadjusted 5-year survival vs. those without PPM (P = 0.0230)

• After risk adjustment, this trend disappeared—likely due to the small sample size (only 26% had self-expanding valves).

The SMART trial and other studies suggest self-expanding valves may offer better hemodynamics in small annuli, making them a valuable option for women.

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Sex-Based Differences: Real-World vs Clinical Trials
A notable finding: men with PPM fared worse than women at 5 years, contradicting older assumptions and highlighting the role of sex-specific physiology and valve-patient interactions.

This emphasizes the need for real-world data to complement clinical trials, especially when making lifetime management decisions in aortic stenosis.

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Clinical Implications & Future Research Directions
Although PPM remains undesirable, this study suggests it may be less clinically impactful after TAVI—especially for women—than previously thought.

Key considerations:

• Individualized valve selection remains crucial.

• PPM should still be avoided when possible, but its presence may not mandate aggressive interventions in women.

• Ongoing trials comparing SAVR with root enlargement vs TAVI in women may further clarify optimal strategies.

As more low-risk and younger patients undergo TAVI, the long-term impact of PPM—and valve choice—will become increasingly relevant.

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Key Takeaways for Clinicians

• Women undergoing TAVI have higher rates of PPM, especially with balloon-expandable valves.

• Despite this, 5-year survival is unaffected, suggesting PPM after TAVI may not carry the same mortality risk as with SAVR.

• Self-expanding valves may reduce PPM incidence in women with small annuli but didn’t confer a clear long-term survival benefit in this study.

• Men may be more adversely affected by PPM than women, highlighting sex-based differences in outcomes.

• Real-world evidence continues to refine valve selection and lifetime planning in aortic stenosis.

Unequal Access to GLP-1 Medications: The Stark Reality for Obesity Care in the U.S.

Introduction:

Despite their game-changing role in obesity and cardiometabolic disease management, GLP-1 receptor agonists remain out of reach for the vast majority of eligible Americans. A recent study analyzing data from over 277 million electronic health records reveals that fewer than 3% of qualifying patients with obesity received these therapies. Even more concerning are the stark disparities based on sex, race, socioeconomic status, and geography. The problem, however, appears rooted not in clinical inertia but in systemic access barriers.

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The Study: A National Lens on Prescribing Trends

Published in JAMA in May 2025, the research by Chungsoo Kim, PharmD, PhD, and colleagues at Yale School of Medicine, analyzed over 39 million U.S. adults with obesity but no type 2 diabetes using the Epic Cosmos Dataset, one of the largest collections of EHR data in the nation.

• Eligibility Criteria: Adults with BMI ≥30 kg/m² or BMI ≥27 kg/m² with one obesity-related comorbidity.

• Study Window: July 2020 to October 2024.

• GLP-1 Agents Tracked: Semaglutide (Wegovy) and Tirzepatide (Zepbound).

Key Findings:

• Only 2.3% (887,110) of eligible patients received a GLP-1 prescription.

• Those prescribed were generally younger (mean 47.3 years) and had a higher BMI (mean 39.0 kg/m²) than those not treated.

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Disparities in Access: Who Is Being Left Behind?

The study uncovered consistent and troubling disparities in prescribing patterns:

1. Gender Disparities

• Women were 2.5 times more likely to be prescribed a GLP-1 agonist than men (3.0% vs 1.2%).

2. Racial and Ethnic Inequities

• Non-Hispanic White: 2.4%

• Non-Hispanic Black: 2.3%

• Hispanic: 1.8%

• Non-Hispanic Asian: 1.7%
  The lower rates among racial and ethnic minorities suggest systemic barriers beyond provider bias, including insurance coverage, affordability, and awareness.

3. Socioeconomic and Geographic Gaps

• Patients in rural regions: 1.5%

• Patients in urban regions: 2.4%

• Those in highly vulnerable socioeconomic areas: 1.9%

• Those in less vulnerable areas: 2.6%

The growth in prescription rates over time was concentrated in metropolitan, affluent areas, with minimal gains in rural or socially disadvantaged communities.

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Not a Physician Problem—It’s a System Problem

Interestingly, clinician access was not the limiting factor. Patients who eventually received a GLP-1 prescription had, on average, five clinical encounters in the preceding year, suggesting that provider interaction alone does not account for the underutilization.

Instead, cost and insurance coverage emerged as key drivers of disparity. The high out-of-pocket price of GLP-1 drugs—often exceeding $1,000 per month—and inconsistent insurance approvals create formidable barriers, especially for marginalized groups.

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Beyond Obesity: Expanding Clinical Promise of GLP-1s

GLP-1 receptor agonists have demonstrated benefit not only in weight loss and glycemic control but also in cardiovascular outcomes, heart failure, atrial fibrillation, and even obstructive sleep apnea. As evidence grows, equitable access becomes not just a health equity issue but a cardiovascular prevention imperative.

Learn more about GLP-1 clinical applications in obesity and cardiometabolic health from the American Diabetes Association and the American Heart Association.

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Conclusion: Call to Action

The glaring gap in GLP-1 utilization reflects deep-rooted systemic inequities, not clinical oversight. As policy evolves and new data emerge, stakeholders—health systems, payers, policymakers, and pharma—must prioritize strategies to expand affordability, coverage, and geographic reach.

Ensuring fair access to life-changing therapies like GLP-1s is not just a matter of good medicine—it’s a matter of health justice.

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Key Takeaways for Clinicians

• Fewer than 3% of eligible U.S. patients with obesity received GLP-1 drugs from 2020 to 2024.

• Significant disparities were seen by sex, race/ethnicity, and geography, independent of provider access.

• Men, minority groups, rural dwellers, and socioeconomically vulnerable populations had markedly lower access.

• Cost and insurance coverage, not physician bias, are the primary barriers.

• As GLP-1 agents show benefit across multiple cardiometabolic diseases, ensuring equitable access is vital to maximizing their public health impact.

Is Left Bundle Branch Area Pacing the Future of CRT?

 New Data Suggests Superior Outcomes Over Biventricular Pacing

Introduction

Cardiac resynchronization therapy (CRT) has long been dominated by biventricular (BiV) pacing, especially for patients with heart failure (HF) and reduced ejection fraction. But as physiological pacing gains momentum, left bundle branch area pacing (LBBAP) has emerged as a potentially superior alternative. Recent results from the International Collaborative LBBAP Study (I-CLAS) presented at Heart Rhythm 2025 further support this shift, offering compelling data favoring LBBAP over traditional BiV pacing.

LBBAP vs BiV: The Study at a Glance

The I-CLAS trial retrospectively analyzed outcomes of 2,579 patients (mean age 70 years, 32% women) with LVEF ≤50%, NYHA class II-IV HF, and QRS ≥130 ms or high ventricular pacing burden. After propensity-score matching, 780 well-balanced pairs were studied.

Key Clinical Outcomes:

• Primary Composite Endpoint (Death or HF hospitalization):

  • LBBAP: 22.2%

  • BiV: 30.8%

  • HR 0.81, 95% CI 0.66–0.99

• Heart Failure Hospitalization Alone:

  • LBBAP: 13.6%

  • BiV: 20.8%

  • HR 0.63, 95% CI 0.49–0.82

• All-Cause Mortality:

• LBBAP: 12.4%

• BiV: 18.2% (NS trend)

Improved Ventricular Function and Arrhythmia Burden

LBBAP showed significantly better LVEF improvement:

• +12% vs +9%

• More patients achieved LVEF gain ≥15% (36% vs 28%, P = 0.004)

Arrhythmic Events (LBBAP vs BiV):

• Non-sustained VT: 4.9% vs 10.9%

• Sustained VT/VF: 4.0% vs 8.1%

• ICD shocks: 3.7% vs 6.8%

• New-onset AF: 2.3% vs 8.5%

These findings underscore LBBAP’s ability to maintain more physiologic ventricular activation, reduce arrhythmogenicity, and potentially lower the need for antiarrhythmic therapies or device interventions.

Procedural Safety and Complications

LBBAP also had a lower procedural complication rate:

• Overall complications: 3.5% vs 6.5%

• Lower incidence of lead dislodgement, pericardial effusion, and infections

Image Source: ACC.org

Practice Implications and Remaining Questions

Despite favorable results, this study was nonrandomized, retrospective, and conducted in high-volume centers with LBBAP expertise. Thus, the generalizability to all clinical settings remains uncertain.

According to experts like Rajesh Kabra, MD, ongoing RCTs and long-term lead performance data are crucial before LBBAP becomes mainstream. Current pacing guidelines by ESC, EHRA, and HRS support conduction system pacing selectively, but individualized patient selection remains the best approach until randomized trial evidence matures.

Key Takeaways for Clinicians

• LBBAP significantly lowers HF hospitalizations and arrhythmic events compared to BiV pacing.

• It leads to greater LVEF improvement and fewer procedural complications.

• While promising, these data stem from observational studies; results from ongoing RCTs are awaited.

• Operator experience and patient anatomy are pivotal in successful LBBAP implantation.

• Until stronger data emerge, tailoring CRT strategy based on patient profile and institutional expertise is recommended.

FDA Greenlights TAVI for Asymptomatic Severe Aortic Stenosis: A Paradigm Shift in Valve Therapy

Introduction

In a landmark decision, the U.S. Food and Drug Administration has approved the use of transcatheter aortic valve implantation (TAVI) using the Sapien 3 platform for asymptomatic patients with severe aortic stenosis (AS). This represents a major shift in the management of AS, driven by compelling evidence from the EARLY TAVR trial.

Groundbreaking Evidence: The EARLY TAVR Trial

The FDA’s decision is anchored in the robust data from the EARLY TAVR trial involving 901 patients. Conducted at multiple centers and led by Dr. Philippe Généreux, this randomized trial compared early intervention with TAVI versus watchful waiting in patients with severe AS but no symptoms.

Key outcomes from the trial:

• Risk of death, stroke, or CV hospitalization was halved with early TAVI (HR 0.50).
• Primary driver of benefit: fewer hospitalizations and urgent interventions in the TAVI arm.
• Notably, 70% of patients in the watchful waiting group required TAVI within 2 years due to symptom progression.

Safety and Clinical Implications

Importantly, early intervention with TAVI did not increase the 30-day cardiovascular mortality, confirming that early treatment is safe even in patients without overt symptoms. Current clinical guidelines, which recommend 6- to 12-month surveillance, may soon require reevaluation.

This regulatory approval is expected to:

• Expand treatment candidacy for TAVI to a broader patient population.
• Encourage earlier referral of asymptomatic patients for structural evaluation.
• Potentially improve long-term outcomes by preempting symptom onset and adverse events.

Key Takeaways for Clinicians

• TAVI is now FDA-approved for asymptomatic severe AS with the Sapien 3 valve.
• The EARLY TAVR trial supports a proactive approach, reducing major cardiovascular events.
• Early TAVI is safe and well-tolerated, challenging the status quo of surveillance.
• This shift may redefine standard care pathways in structural cardiology.