Month: June 2024

Cardiology in H1 2024

Posted on by Jake Fishman

The first half of 2024 is now a wrap, and it was another big one in cardiology. Here are some of Cardiac Wire’s top six storylines from the last six months, plus some things to keep in mind as we head into 2024’s second half:

  • A Sick World – Over the course of H1 we’ve learned that 90% of US adults are at risk of developing cardiovascular-kidney-metabolic syndrome, artificial sweeteners that we consume every day are associated with increased CVD risks, many patients might have microplastics embedded in their plaque, and the number of Americans with CVD will surge by 60% during the next 25 years. Yikes.
  • TR Options – H1 brought the FDA approvals of Edwards’ EVOQUE transcatheter tricuspid valve replacement system and Abbott’s TriClip tricuspid edge-to-edge repair (TEER) system, giving US interventionalists the options to repair or replace the tricuspid valve for the first time. That’s a big change after years of only having surgical TR options, and it appears that more interventional TR devices are on the horizon.
  • GLP-1s are for CVD too – So far this year GLP-1s have gone from a weight loss and diabetes drug that “might” have cardiovascular benefits to becoming an FDA-approved and Medicare-covered option for CV event reduction. GLP-1s’ cardiovascular impact is likely to continue to expand, given growing evidence that it also improves HF symptoms.
  • Pulsed Field Awakening – Pulsed field ablation was the clear electrophysiology highlight of 2024 so far, after dominating conversations at HRS 2024, producing mounting evidence of its advantages, and scoring its first FDA approval.
  • AI Impact – Cardiology might not be the first specialty that comes to mind when discussing healthcare AI, but cardiovascular AI products are seeing major product, reimbursement, and adoption progress this year. We’re also seeing AI play a greater role at cardiovascular conferences, and a steady expansion of cardiovascular AI products beyond imaging and ECG modalities.

Shockwave Therapy’s Ischemic Heart Failure Potential

Posted on by Jake Fishman

New research out of Austria suggests that cardiac shockwave therapy could help address ischemic heart failure patients’ myocardial regeneration challenges, allowing meaningful LVEF and quality of life improvements, and potentially better outcomes.

  • Chronic ischemic heart failure patients are commonly treated with CABG revascularization, which helps control symptoms, but is less effective at improving LVEF. 
  • Shockwave therapy (SWT) transmits sonic pressure waves, generating a physical stimulus that’s shown to improve regeneration of ischemic myocardium in animal models, and has been used to treat humans for a range of conditions (tendonitis, leg ulcers, wounds, spinal cord injury, ED). 

With this in mind, Innsbruck University spin-off Heart Regeneration Technologies developed a SWT system that applies shock waves directly to patients’ hearts, with the goal of improving cardiac function by inducing angiogenesis and myocardium regeneration.

The new CAST-HF trial suggests that Heart Regeneration Technologies’ SWT combined with CABG does indeed lead to major LVEF improvements. 

The researchers randomized 63 patients with ischemic heart failure (LVEF ≤40%) to undergo CABG plus SWT or CABG plus a sham procedure, finding that at one year the SWT group had…

  • Greater improvements in LVEF (11.3% vs. 6.3%), the primary endpoint
  • Greater improvements in the 6-minute walking test (+127.5 vs. +43.6 meters)
  • Lower MLHFQ scores (11 vs. 17.3 points)

SWT’s potential was actually visible by six months, when it already had notable improvements to LVEF (10.5 vs. 5.7) and both of the quality of life metrics, with no device-related adverse or serious adverse events throughout the entire period. 

  • The SWT step also only takes about 10-15 minutes, and is performed during the usual reperfusion time, so it doesn’t affect anesthesia or operating times.

These are encouraging results to say the least, noting the strong association between better LVEF and improvements in survival and hospitalizations.

The next step is to hold larger trials to confirm if SWT’s myocardial function improvements actually translate to better outcomes, although Heart Regeneration Technologies is already targeting European regulatory approval by late 2024 and the first non-trial patient treatments in 2025.

The Takeaway

There’s still more to prove, but these results suggest that cardiac shockwave therapy could drive significant improvements for patients with chronic ischemic heart failure.

New Echo AI Model Could Streamline Mitral Regurgitation Diagnosis

Posted on by Jake Fishman

Columbia and Cornell researchers developed an echo AI model that could improve the difficult task of mitral regurgitation diagnosis, and might even represent an AI-driven step towards enhancing all valvular regurgitation assessments.

  • Transthoracic echocardiography is the go-to modality for mitral regurgitation diagnosis, but these exams are difficult to perform and prone to high variability.

The researchers set out to solve this problem using AI, and indeed showed that AI could perform MR exams at the same level as academic echo labs.

Using 52,702 Columbia-sourced TTEs for model training and validation, the researchers developed their end-to-end AI system to intake complete TTE studies, identify color MR Doppler videos, then accurately determine MR severity on a 4-step scale (none/trace, mild, moderate, and severe). 

They then tested their AI against 8,987 TTEs from an internal Columbia dataset and 8,208 TTEs from an external Cornell dataset, finding that the model achieved high…

  • Agreement with cardiologist interpretations – 82% & 79% accuracy (k = 0.84 & 0.80)
  • Performance for detecting moderate/severe MR – 0.98 & 0.98 AUROCs

Most misclassification disagreements between the AI and cardiologists involved exams with none/trace or mild MR, while the AI maintained robust performance across different MR types (slightly lower with eccentric MR cases).

  • When the AI and cardiologist disagreed, an adjudication panel sided with the AI and cardiologists about a quarter of the time each, while half the time they thought the answer was in the middle.
  • The researchers also found that AI trained to use multiple TTE views outperformed models using the apical 4-chamber view (82% vs. 80%).

Next up, the researchers plan to continue their echo AI efforts, including expanding to other valvular and cardiac assessments, and bringing their research into clinical settings.

The Takeaway

Echocardiography has long been an AI hotspot due to its importance, prevalence, and its challenges with efficiency and variability, but most clinical-level echo AI solutions have focused on heart failure and aortic stenosis so far. Although Columbia and Cornell’s new AI model is still in its early stages, this study makes a solid case for how much more echo AI can help, including across a full range of valvular regurgitation assessments.

Marea Therapeutics’ Cardiometabolic Mission

Posted on by Jake Fishman

Marea Therapeutics emerged this week, announcing $190M in Series A/B funding and a mission to develop “a new generation of medicines for cardiometabolic diseases” – starting with their drug candidate targeting remnant cholesterol.

Marea got its start from a tweet by UCSF cardiologist Ethan J. Weiss, MD, regarding his interest in metabolism and a protein (Angptl4) that blocks lipoprotein lipase (LPL) and regulates how the body stores fat.

  • A follow-up Twitter comment directed Dr. Weiss to a Novartis molecule that targets Angptl4, and by 2022 Weiss had co-founded Marea Therapeutics and licensed the drug candidate from Novartis.
  • Since then, Marea has assembled a solid founding team, and gained backing by some of the biggest investors in life sciences.

They have also turned that Novartis drug candidate into their lead program, MAR001, a monoclonal antibody that targets ANGPTL4, and is intended to address the untreated lipid and metabolic drivers of cardiovascular events in high-risk patients.

Marea believes that by blocking Angptl4 and altering its LPL activity, MAR001 could lower remnant cholesterol, correct adipose tissue, and bring improvements to triglyceride distribution, metabolic function, and insulin sensitivity — potentially reducing cardiovascular events. 

  • That’s different from most current cholesterol approaches that mainly target LDL reduction, but previous research has shown that remnant cholesterol carries cardiovascular risks that are independent of LDL-C, apoB, and other traditional risk factors.
  • Despite this evidence, there are currently no other available targeted therapies for remnant cholesterol reduction and improving metabolic function.

Marea still has to prove MAR001’s performance, although in its Phase 1 trial MAR001 significantly lowered remnant cholesterol levels and improved metabolic biomarkers. 

  • Results from its current Phase 1b/2a trial is due to be completed by the end of 2024, and its Phase 2b trial is scheduled to start in early 2025.

Marea’s pipeline will also extend beyond MAR001, as it develops other candidates targeting “untapped nodes driving cardiometabolic diseases.”

The Takeaway

Nothing happens fast in cardiology, and that’s especially true for brand new cholesterol and cardiometabolic approaches. That said, five million cardiovascular patients in the U.S. have elevated remnant cholesterol – and none of them are receiving remnant cholesterol treatments – so Marea’s efforts might be worth waiting for.

The Rise of Private Equity Cardiology Practice Acquisitions

Posted on by Jake Fishman

New research in JAMA highlighted the rapid growth of private equity-backed cardiology practice acquisitions, while revealing some interesting geographic factors driving this growth.

The PE acquisition trend started slowly, with just one PE-backed acquisition of a seven-location cardiology practice in 2019, followed by an acquisition of another small practice in 2020. 

  • Subsequent years brought more and larger acquisitions, culminating in 2023 when PE platforms acquired 35 practices with roughly 220 combined locations.
  • All together, PE firms acquired 50 practices with 320 locations between 2019 and 2023.

This run of cardiology practice acquisitions spanned 22 states, but largely targeted practices in Florida (80), Texas (76), and Arizona (29) due to those states’ size, demographics (e.g older patients), and regulatory environments (e.g. rules for opening new ASCs). 

  • In fact, there’s now seven states where PE-acquired practices account for more than 10% of all cardiology practices, including Rhode Island (13 of 35), Nevada (14 of 53), Louisiana (21 of 89), Arizona (29 of 165), Oklahoma (13 of 82), Texas (76 of 675), and Florida (80 of 798).
  • Those geographic trends were largely driven by the two largest PE-backed platforms –  Cardiovascular Associates of America and US Heart & Vascular – which operate all PE practices in seven states (AZ, GA, IA, KS, NJ, RI, SC) and over 60% of PE-acquired practices in Florida, Georgia, and Texas.
New research in JAMA highlighted the rapid growth of private equity-backed cardiology practice acquisitions, while revealing some interesting geographic factors driving this growth.

Despite PE’s momentum, these acquisitions represent just 3.9% of cardiology practice locations in the US (330 of 8,223), and there’s reason to believe that 2023’s acquisition pace might not continue going forward.

  • So far in 2024 we’ve only identified four PE acquisitions, with three from CVAUSA, and just one by Cardiovascular Logistics… although it’s likely that other unannounced acquisitions happened this year.
  • Additionally, many cardiology practices have already consolidated into hospital or corporate-owned groups, leaving just 10k of the US’ 33k cardiologists within independent practices (80% of them working in practices with under 10 physicians).

That creates a very different acquisition environment than seen with specialties that underwent major private equity consolidations (e.g. radiology or dermatology), and will likely force PE platforms to target both private and hospital-employed groups.

The Takeaway

Private equity’s massive expansion across US healthcare largely skipped cardiology before 2021, but recent trends suggest that PE will have a much greater influence within cardiology going forward — especially in PE-friendly states.

New Calculations Could Slash Statin-Eligible Population

Posted on by Jake Fishman

A JAMA paper suggests that if the CVD guidelines adopt the AHA’s new PREVENT cardiovascular risk equations, it might slash the US’s eligible preventive statin user population by nearly 40%.

In November 2023 the AHA launched the PREVENT risk equations, which take into account a wider range of cardiovascular, kidney, and metabolic health measures to estimate 10- and 30-year risks of heart attack, stroke, and heart failure. 

  • The new equations notably added sex-specific risks and cardiovascular-kidney-metabolic syndrome metrics, while eliminating race since it’s not a biological factor.
  • The PREVENT calculator also represented a big change from 2013’s Pooled Cohort Equation (PCE), which was released before many CKM treatments were available, and faced criticism for overestimating CVD risks.

To evaluate PREVENT’s impact, the researchers applied the PREVENT and PCE equations to 3,785 adults aged 40 to 75 years without known ASCVD, 20.7% of whom currently take statins…

  • Patients had far lower estimated 10-year ASCVD risks with the PREVENT equations compared to the PCEs (4.3% vs. 8%).
  • The PREVENT equations’ estimated risks were lower across all age, sex, and racial subgroups.
  • PREVENT’s risk reductions were greatest among Black adults (5.1% vs. 10.9%) and people between 70 and 75 years (10.2% vs. 22.8%).
  • The PREVENT equations reclassified very few patients as higher risk for ASCVD, and most were classified to lower risk groups.

Add that all together, and transitioning to the PREVENT equations could reduce the number of Americans who meet the criteria for primary prevention statin therapy from 45.4M to 28.3M, while allowing 4.1M adults who are currently taking statins to get off their meds. 

The PREVENT equations aren’t included in the CVD guidelines yet, but their addition is expected by many, and the AHA has already launched a PREVENT calculator that’s intended for clinician use.

The Takeaway

There’s a good chance that the new PREVENT equations will have a major impact on patient care, reducing the number of low-risk patients who are prescribed statins, while hopefully increasing statin adherence among the highest-risk patients.

Edwards’ Strong Five-Year Small Annulus TAVR Outcomes

Posted on by Jake Fishman

Edwards Lifesciences and Medtronic’s fight for TAVR supremacy took an interesting turn last week, after Edwards showed that its SAPIEN 3 valve has similar five-year outcomes among patients with both small and large aortic annulus, regardless of their mean gradients and rates of prothesis-patient mismatch (PPM).

The study analyzed 1,355 low or intermediate risk patients with symptomatic aortic stenosis who received an Edwards SAPIEN 3 balloon-expandable valve and were included in the PARTNER 2/S3i registry or PARTNER 3 trial. Roughly a third of those patients (476) had a small aortic annulus (≤ 430 mm2).

After five years, patients with small and large aortic annulus had…

  • Similar rates of death/disabling stroke – 36.3% vs. 35.8%
  • Similar all-cause mortality – 28.5% vs 29.3%
  • A nonsignificant difference in aortic valve reintervention – 2.7% vs. 1.8%
  • Similar rates of bioprosthetic valve fracture – 2.9% vs. 2.1%

When analyzing small annulus patients based on PPMs and mean gradients (≥20 mm Hg), there was no difference in stroke and all-cause mortality metrics, nor were there differences in reintervention and bioprosthetic valve fracture. 

Although Medtronic wasn’t mentioned, it’s easy to view these results as a response to the recent SMART trial, which found that Medtronic’s Evolut self-expanding valve had key one-year advantages over Edwards’ SAPIEN 3 valves in patients with small aortic annuli. 

  • In the SMART trial, the devices had similar rates of death, disabling stroke, or HF hospitalization (9.4% vs. 10.6%). However, Medtronic’s Evolut had much lower bioprosthetic-valve dysfunction (9.4% vs. 41.6%), hemodynamic structural valve dysfunction (3.5% vs. 32.8%), and aortic-valve mean gradient (7.7 vs. 15.7 mm Hg).

Many people walked away from that ACC Late Breaker with a hunch that the Evolut might prove to be better for people with small aortic annuli. However, we’re going to have to see the SMART trial’s five-year results to know for sure, or better understand whether metrics like gradients and PPM actually affect outcomes.

The Takeaway

While the SMART trial might have shown early signs of the Evolut valve’s hemodynamic advantages in small aortic annuli patients, Edwards new five-year SAPIEN 3 data suggests that there might not be an association between PPM or mean gradients and actual clinical outcomes. At least for now, we don’t have any long-term data that suggests otherwise.

Philips Expands & Integrates Echo AI Platform

Posted on by Jake Fishman

Philips’ ultrasound AI strategy took another big step this week, with the launch of its next-generation echo AI platform, which will come integrated with the company’s cardiovascular ultrasound systems and bring a range of new echo-automating capabilities. 

Philips’ new AI-enabled cardiovascular ultrasound platform includes a combination of established and first-to-market AI applications that come fully integrated with its EPIQ CVx and Affiniti CVx echo scanners, with a focus on speeding up echo teams’ cardiac ultrasound analysis.

The announcement specifically highlighted Philips’ first-of-their-kind…

  • Segmented Wall Motion app – an automated tool for segmental wall motion scoring and identifying disorders such as coronary artery disease and cardio-oncology issues.
  • 3D Mitral Regurgitation Volume Quantification app – a tool for the automated analysis of MR flow dynamics, supporting valve treatment decision-making (not yet FDA cleared).

The platform also includes solutions for automated LVEF measurements, LV strain analysis, and the automated selection of the most appropriate LV images.

Philips has been developing echo AI solutions for some time through its ultrasound and Tomtec teams, and boosted its echo AI portfolio and development capabilities through its acquisition of DIA Image Analysis almost exactly one year ago.

However, this launch is perhaps most notable for bringing the “deep” integration of AI tools into Philips’ cardiovascular ultrasound systems, making AI a core part of its scanners’ feature set and value proposition, rather than an add-on.

  • That integration could be particularly notable from a usability perspective, and could also help drive AI adoption given the continued barriers experienced when selling / buying AI as standalone solutions. 
  • It might also be a sign of an echo AI integration trend, noting that GE HealthCare has been steadily expanding its Caption AI echo guidance solution to more of its echo scanners since acquiring Caption Health last year.

The Takeaway

With all the imaging AI acquisitions that have taken place over the last few years, Philips’ echo AI integration is a reminder why the only acquisitions made by the big OEMs targeted cardiovascular ultrasound AI solutions (no other indications or modalities). 

AI tools like these make cardiovascular ultrasound systems faster and easier to use, and scanner integrations like these might have a multiplying effect on echo AI’s adoption and overall impact.

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