Nemours Children’s Hospital Chief of Pediatric Cardiology, Gul Dadlani, MD on why ECG screening is gaining momentum with teen athletes.

Cardiology Pharmaceuticals

Zilebesiran Phase 2 Results Show Long-Lasting Blood Pressure Impact

Zilebesiran’s path towards becoming the first long-lasting antihypertensive medication gained more momentum, with new topline Phase 2 results demonstrating that a single injection significantly reduces systolic blood pressure through six months.

Alnylam Pharmaceuticals’ Zilebesiran is an investigational RNA interference therapeutic agent that inhibits hepatic angiotensinogen synthesis, which plays a key role in hypertension development. 

• Perhaps more notably, zilebesiran’s ability to control blood pressure over long periods could address the daily medication adherence challenges that often undermine hypertension care.

Zilebesiran is wrapping up an epic summer, starting with a Phase 1 trial showing that one injection can control blood pressure for up to six months, which was quickly followed by a co-development and co-commercialization alliance with Roche that’s worth up to $2.8B, and culminating with these new Phase 2 results from its KARDIA-1 trial.

The KARDIA-1 trial randomized 394 adults with untreated hypertension or taking one or more anti-hypertensive medications into one of five treatment arms, and followed them over 12-month and extended double-blind periods. 

• 150 mg zilebesiran every six months
• 300 mg zilebesiran every six months
• 300 mg zilebesiran every three months
• 600 mg zilebesiran every six months
• Placebo, followed by zilebesiran after six months

The 300 mg and 600 mg zilebesiran groups achieved the study’s primary endpoint, with at least 15 mmHg lower 24-hour systolic blood pressure levels than placebo patients (p<0.0001).

All zilebesiran groups also met key secondary endpoints, including significant changes in mean 24-hour SBP at six months and in office SBP at three and six months.

Like the Phase 1 trial, the KARDIA-1 trial’s zilebesiran group had a lower rate of serious adverse events than the placebo patients (3.6% vs. 6.7%), and no serious events were believed to be related to the drug.

Alnylam highlighted these Phase 2 results as more evidence of zilebesiran’s safety and sustained efficacy, supporting the drug’s continued research and development.

The Takeaway

Although zilebesiran has a lot more to prove, its initial Phase 1 and 2 results (along with its big support from Roche) show that it’s making solid progress towards becoming the first long-lasting antihypertensive medication. Given the challenges with bringing many patients’ hypertension under control, that could be a big deal.

Accurately Measuring Heart Rate Variability

Heart rate variability measurement and analysis involves two critical elements – the ability to accurately discern the R wave in noisy environments, and using the correct analysis method for a given application. Check out how Monebo’s Kinetic HRV ECG Algorithm excels at both of these essential tasks.

Us2.ai’s Heart Failure Screening Impact

See how Us2.ai’s echo AI solution improved heart failure screening in the NHS, reducing echo waiting times from 12 months to under 6 weeks.

The Wire

• Teen ECG Screening: Axios explored the trend towards testing teen athletes for heart conditions via ECG screening, driven by recent high-profile cardiac arrest cases and an alarming estimate that up to 80k teen athletes suffer fatal cardiac arrests annually. Although experts warn against the inefficiencies and risks that would come with screening all teen athletes, the article noted that “sudden cardiac death is still the top medical cause of death in athletes,” and cited a recent study showing that 3% of 11,500 student athletes in central Florida had abnormal ECG results.

• WATCHMAN FLX Pro FDA Approval: Boston Scientific announced the FDA approval of its new WATCHMAN FLX Pro Left Atrial Appendage Closure (LAAC) Device, which adds a number of new features and design elements to improve upon the well-established WATCHMAN FLX platform. Specifically, the WATCHMAN FLX Pro now features a polymer coating (reduces thrombus & supports healing), visualization markers (enhances device placement), and a broader size matrix (supports wider range of patients).

• Better Outcomes From Female Surgeons: A study in JAMA Surgery found that patients’ chances of a poor postoperative outcome, including death, are significantly lower if their surgeon is female. Of the one million patients included in the study, those treated by the 2,306 male surgeons were a whopping 25% more likely to die within 90 days than those treated by 700 female surgeons. The difference seemingly stems from performance outside the OR, such as women physicians better-preparing patients for surgery.

• Catheter Ablation Improves End-Stage HF Afib Outcomes: Results from the CASTLE-HTx trial strongly support the combination of catheter ablation and guideline-directed medical therapy for treating patients with Afib and end-stage heart failure. The study randomized 194 patients to either undergo catheter ablation or only receive medical therapy. After a median of 18 months, the ablation group had a far lower composite endpoint rate (8% vs. 30% = death, LV assist device implant, or urgent heart transplant) and a lower all-cause mortality rate (6% vs. 20%).

• Corteria’s HF Funding: French biopharma Corteria scored $71M in Series A financing that it will use to advance its heart failure therapy pipeline. Corteria was founded in 2021 by a pair of Sanofi cardiovascular leaders, and currently has three HF therapy candidates: 1) a once-daily subcutaneous CRF23 agonist for worsening heart failure, 2) a once-monthly subcutaneous CRF23 agonist for right heart failure; and 3) An AVP (arginine vasopressin) neutralizing monoclonal antibody for acute heart failure with hyponatremia.

• HF Hospital at Home: Home-based care might be better for many patients with worsening heart failure, but this innovative approach still faces significant hurdles. That’s from a Circulation: Heart Failure paper that detailed hospital at home (HaH) care’s HF advantages (similar care at lower-costs, no isolation from family). However, HaH for worsening HF largely remains limited because it’s currently appropriate for a small portion of patients, and would require new and more-permanent reimbursements, better research evidence, improved patient selection models, and greater patient/family readiness.

• FDA to Modernize 510(k) Rules: The FDA is planning to modernize its 510(k) program, one of the most popular regulatory paths to market for lower-risk cardiology products. The agency issued draft guidances in three areas: 1) selecting a predicate device for 510(k) submissions, 2) using clinical data in applications, and 3) evidentiary expectations for 510(k) implant devices. The FDA also noted that starting October 1, all 510(k) applications must be submitted electronically with its eSTAR process.

• Redo-TAVR Evidence: A large Lancet registry study provided perhaps the strongest evidence yet supporting redo-TAVR, when using more modern balloon-expandable transcatheter valves. Analysis of 350k patients who underwent redo-TAVR or native-TAVR between 2011 and 2022 (1,320 redo-TAVR) found that redo-TAVR had low procedural complication rates that were similar to native-TAVR, with no significant differences in death or stroke at 30 days (4.7% vs 4.0%; 2.0% vs 1.9%) and similar moderate or severe aortic regurgitation rates at 1 year (1.8% vs 3.3%).

• Vektor’s vMap Updates: Vektor Medical added a range of enhancements to its AI-based vMap solution, which supports EP procedures by mapping arrhythmias using 12-lead ECG data. The new vMap software features directly target automation and advanced visualization, including Beat Assist (recommends beats of interest that might be arrhythmia source), Upgraded Heart Model (more realistic and detailed representation of the heart), and Automated ECG Baseline Correction (removes baseline noise from input ECG signals).

• Semaglutide’s T1D Impact: We might be able to add type 1 diabetes to semaglutide’s list of managed diseases, in addition to T2D, obesity, and CVD. In a small 10-patient study with potentially life-altering implications, all patients who began taking low-dose semaglutide shortly after their diagnosis were able to discontinue post-meal insulin within three months, while seven of the patients were able to stop taking daily insulin. The group’s HbA1C also dropped from 11.7% to 5.9%. This small study earned a big reaction from the medical community, and should pave the way for larger trials.

• Hiring Top Exec Concern: Healthcare workforce challenges unfortunately aren’t going anywhere soon, with PwC’s August Pulse Survey finding that 8 in 10 healthcare executives still view hiring and retaining talent as their organization’s top risk. Health execs were more likely to report workforce concerns than the average across all industries (82% vs. 71%), but PwC still expects more layoffs, strikes, and rate increases as long as inflationary pressures continue.

The True Measure of Cardiac Risk

How can AI help physicians “see” beyond conventional lipid profiles? Tune in to this upcoming webinar, examining how Cleerly’s AI-QCT solution complements conventional approaches to evaluating heart disease risk factors, and improve coronary artery disease diagnosis and heart attack risk assessments. Reserve your spot today in order to join live on September 21st.

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 Resource Wire

• Gain in-depth knowledge of fluoroscopic anatomy and cutting-edge imaging techniques with renowned expert, Dr. Nicolo Piazza. This five-session master class is happening now through November. Register now!

• Looking to optimize your cardiovascular imaging services, but don’t know what to measure? Check out this Change Healthcare report for insights on how to track and evaluate your cardiovascular imaging performance, assess quality, and enhance operational efficiency. Read the full article now and start measuring what matters!

• What happens when HeartFlow’s FFRCT Analysis is adopted nationwide? See how the NHS’ nationwide implementation of HeartFlow’s FFRCT solution led to significant reductions in cardiovascular and all-cause mortality, plus solid efficiency gains.