James Januzzi, MD after the official release of aficamten’s SEQUOIA-HCM trial results.

Heart Failure

Aficamten Shines in SEQUOIA-HCM Trial

Cytokinetics’ obstructive hypertrophic cardiomyopathy drug aficamten excelled in its SEQUOIA-HCM Phase 3 trial, significantly improving peak oxygen uptake, while achieving all secondary effectiveness and safety endpoints.

• HCM causes the heart muscle to become abnormally thick, limiting the heart’s pumping function, while leading to reduced exercise capacity and increased CV risks.
• Aficamten is a selective cardiac myosin inhibitor that treats HCM by reducing active actin-myosin bridges during each cardiac cycle, thus suppressing myocardial hypercontractility.
• HCM care appears to be entering a new era, following the 2022 approval of Bristol Myers Squibb’s Camzyos, significant HCM awareness efforts from BMS, and the HCM treatment guidelines’ recent addition of myosin inhibitors (like Camzyos and aficamten).

SEQUOIA-HCM had all the makings of a well-designed trial (randomized, placebo-controlled, dose-adjusted, double-blind, multicenter, international, 40.8% women) and showed powerful improvements among 282 randomized HCM patients during 24 weeks of treatment. 

Patients in the aficamten group achieved a far greater change in peak oxygen uptake versus placebo (1.8 vs. 0.0 mcg/kg/minute), which was the primary endpoint, while significantly improving all 10 secondary endpoints.

• Highlighted secondary endpoint improvements included: KCCQ-CSS (+7 points), increase of at least NYHA class (58.5% vs. 24.3%), reduced LVOT-G after the Valsalva maneuver (–50 mm Hg), and proportion of patients with <30 mm Hg LVOT-G after the Valsalva maneuver (49.3% vs. 3.6%).
• Aficamten’s impact on exercise capacity appeared to be similar across subgroups, including patients who were severely symptomatic (NYHA class III or IV heart failure) and functionally limited (peak oxygen uptake of ≤18 mcg/kg/minute). 
• Aficamten also proved to be well-tolerated, with similar adverse events as the placebo, and no instances of worsening heart failure or treatment interruptions due to low LVEF.

Many HCM watchers are particularly interested in how aficamten compared to mavacamten (BMS’ Camzyos), and SEQUOIA-HCM showed similar benefits overall. However, unlike mavacamten, aficamten maintained its performance among patients on beta-blockers, and its shorter half-life allowed faster dose escalation (and faster effective dose identification).

The Takeaway

The complete SEQUOIA-HCM results suggest that a new and potentially more effective treatment option for symptomatic obstructive HCM is on the way, which could prove to be a big deal for the 680k to 1.1M HCM patients in the U.S and a very big deal for the Cytokinetics.

A CCTA-Based Approach to Heart Attack Prevention

Cardiologists are increasingly relying on cardiac CT angiograms as a heart disease diagnostic tool. See what’s driving this trend in this Cleerly report detailing the key attributes of CCTA exams, evidence of its effectiveness, and CCTA’s medical guideline support.

The Benefits of Outsourced Post-Processing

Using an outsourced cardiac image post-processing solution doesn’t have to mean sacrificing control of the results. Discover how PIA’s customizable post-processing workflow can help you get the most out of your images.

The Wire

• Wynn Hospital Pauses Open Heart Surgeries: Upstate New York’s Wynn Hospital temporarily paused its open heart surgeries after receiving an “immediate jeopardy” notice from New York State Department of Health inspectors, a rare notification reserved for programs that have caused or are likely to soon cause patient injury. Wynn will continue to perform all other cardiac services and procedures, but won’t reopen its open heart surgery program until an external review is completed, while suggesting that firing its two cardiac surgeons is “definitely a possibility.” 

• Traditional Lipids Can’t Replace ApoB: A study of nearly 300k adults suggests that lipid markers aren’t a suitable proxy for apolipoprotein B, which is the most accurate marker for ASCVD risk. The study found that LDL-C, non-HDL-C, and triglycerides correlated with ApoB levels, but these markers had significant variability in measured ApoB. For example patients with a triglyceride level of 115 mg/dL had ApoB levels ranging between 67.8 and 147.4 md/dL.

• Medtronic Adds AI to LINQ ICMs: Medtronic added its artificial intelligence-based AccuRhythm AI solution to all of its Reveal LINQ ICMs in the United States, Australia, and New Zealand, with a European rollout coming later this year. Medtronic expects that AccuRhythm AI will reduce false AFib and atrial pause alerts by 85%, while preserving true alerts at 98.2% and 99.9% rates, thus saving 186 hours of false alert reviews annually for every 200 patients.

• TAVR’s Cardiogenic Shock Benefits: The use of TAVR in patients with aortic stenosis and cardiogenic shock has increased over the last several years while SAVR procedures have declined. A new SCAI study suggests that this shift is partially due to TAVR’s lower risk of stroke (OR=0.48), kidney injury, and bleeding, with similar mortality rates as SAVR. The real benefit, though, was that TAVR allowed for shorter hospital stays and lower costs, making it a more than feasible treatment option for this high-risk population.

• Acoramidis’ ITT Improvements: New analysis from the Phase 3 ATTRibute-CM study further highlighted the efficacy and safety of BridgeBio Pharma’s ATTR-CM treatment acoramidis. Among the study’s intention-to-treat population (N=632), acoramidis significantly reduced all-cause mortality (p=0.04), while the drug was associated with a 25% lower risk of death among 21 high-risk participants with Stage 4 chronic kidney disease. Acoramidis use showed no clinical safety concerns with either group.

• Preventing Tech Team Injuries: Preventing MSK injuries among allied health staff in interventional and echocardiography labs could be as simple as having them perform routine stretching exercises. Mayo Clinic researchers had 68 technologists and nursing staffers complete a 15-minute daily stretching routine for one year, after which participants reported a decrease in median Disability of Arm, Shoulder, and Hand (DASH) scores (5.2 to 2.6).

• A Case for TAVR NDD: An AHA study showed promising outcomes for patients who undergo TAVR with Medtronic’s Evolut valves and are discharged the following day. Next-day discharge (NDD) was associated with lower 30-day readmission rates (6.3% vs. 8.4%) and better 1-year outcomes than patients discharged beyond one day, including reduced mortality and fewer complications. NDD rates also increased from 45.4% to 62.1% between the first and last quarters of the 2019-2021 study period (n=29,597).

• GE Adds Medis QFR: GE HealthCare and Medis Medical Imaging launched a new partnership that will make the Medis Quantitative Flow Ratio (Medis QFR) solution available to cath labs via GE’s Allia interventional cardiology platform. Medis QFR uses angiography analysis to provide cath lab teams with image-based physiology of coronary obstructions, helping them determine if a PCI is required, select which lesions should be treated, and create their PCI treatment plan.

• Claims-Based MACE Predictor: A novel prediction model using real-world data from medical and pharmacy claims accurately predicted 1-year MACE risk for 6.6M adults with type 2 diabetes (concordance index of 0.74). The ACME model integrates 30 variables to forecast MACE events, addressing major limitations of standard prediction models, including reliance on data that may not be routinely available.

• PFA Is Durable Despite Redos: New findings from a European study examining pulsed-field ablation (PFA) for AFib found that while 23% patients had arrhythmia recurrence leading to redo procedures, 71% of pulmonary veins maintained durable isolation during the redo. Operator experience mattered, as those with prior cryoballoon ablation experience had higher durability rates. However, neither operator experience (>5 years vs. <5 years) nor PFA device size significantly affected outcomes.

• Early Preeclampsia Risk Screening: A Fetal Medicine Foundation (FMF) screening algorithm that combines biophysical, biochemical, and ultrasound markers successfully detected preeclampsia risk in early pregnancy. In the PREDICTION study of 7,554 participants who were in the first trimester, the FMF algorithm’s detection rates were about 63% for preterm preeclampsia and 77% for early onset preeclampsia, with 16% false positives.

Advance Your Vessel Analysis

Ready to advance your EVAR planning? See how you could leverage TeraRecon’s EVAR (Vessel Analysis) package to streamline and enhance your complex aortic intervention planning.

Us2.ai’s Contrast Echo Correlations

Check out what might be the first study evaluating the performance of AI-automated contrast echocardiography exams, which found that Us2.ai’s echo AI solution produced LV measurements with “good to excellent agreement” with human experts.

The Resource Wire

• Incidental CAC Predicts Long-Term Risks: What if you could identify which of your asymptomatic patients have high risks of future cardiac events? Stanford-led researchers used Bunkerhill Health’s Incidental CAC algorithm to do just that, finding that patients with ≥100 incidental CAC scores had a 24% 10-year risk of developing ASCVD and far higher risks of major adverse events.

• ECG Data You Can Trust: Noise and artifacts can make automated ECG analysis less reliable than what’s required for the exacting standards of cardiac safety trials. Monebo’s Kinetic Intervals ECG Algorithm provides precise interval measurements between any two points on the ECG waveform, allowing clinicians to utilize data they can trust.

• Experience the future of learning: Medtronic Academy 2.0 is here! Unlock your ultimate destination for structural heart medical education with the newly redesigned Medtronic Academy 2.0. Gain access to expert-led courses, webinars, and a wealth of resources to stay ahead in cardiovascular care. Visit now!

• A Solution for Your Entire Cardiology Service Line: The pace of change in healthcare can be dizzying, creating new and more complex challenges for cardiology departments to overcome. See how Merge Cardio and Merge Hemo can turn those challenges into opportunities for greater workflow efficiency and improved care.

• Advancing CAD Risk Assessments: When HeartFlow used its Plaque Analysis solution to analyze more than 11,000 CCTAs in the DECODE Study, the solution achieved 95% agreement with IVUS and led to changes in two out of every three patients’ treatment plans. See how HeartFlow Plaque Analysis can help you accurately assess your patients’ CAD risks and personalize their treatment.