RECOVER IV investigator William O’Neill, MD to TCTMD, after his Impella trial was halted.

There are few areas of healthcare with more innovation than artificial intelligence, but most of those solutions never make it past being published in a medical journal – providing no additional value to medical care or the solutions’ developers. In the latest Cardiac Wire Show, Bunkerhill Health CEO Nishith Khandwala discusses Bunkerhill’s unique approach to solving this problem and the impact they are having in cardiology, radiology, and beyond.

Pharmaceuticals

Marea Therapeutics’ Cardiometabolic Mission

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.

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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.

The Bunkerhill Blueprint

Advancing an AI solution from concept to clinic used to take years, but Bunkerhill Health is closing that gap at lightning speed. See how Bunkerhill is streamlining AI training, validation, approval, and commercialization to get better AI tools into clinical practice, faster.

The Wire

• Pregnancy Hypertension Rising: New research published in AHA suggests that the prevalence of chronic hypertension during pregnancy doubled in the U.S. between 2008 and 2021, jumping from 1.8% to 3.7% of pregnancies (n=1.9m). The use of antihypertensive medication among pregnant individuals with chronic hypertension remained stable at between 57% and 60%, while increases in labetalol use (up from 19% to 42%) made it the most common antihypertensive during pregnancy, replacing methyldopa (down from 29% to 2%).

• IV AAs Reduce AKIs After Cardiac Surgery: In a recent multinational trial, IV amino acids significantly reduced cardiac surgery patients’ acute kidney injury (AKI) rates. Among 3,511 adults undergoing cardiac surgery, those who received amino acids had a far lower incidence of AKI compared to placebo (26.9% vs. 31.7%). Notably, severe AKI (Stage 3 AKI) was 44% less frequent with patients in the amino acids group.

• Elixir’s Breakthrough Status: Elixir Medical’s DynamX sirolimus-eluting coronary bioadaptor system landed FDA Breakthrough Device designation, potentially streamlining the implant’s path towards approval. The designation specifically targets improving coronary luminal diameter, restoring hemodynamic modulation, and reducing plaque progression in patients with symptomatic ischemic heart disease. Elixir Medical has reason to be optimistic about the DynamX, after 2-year outcomes showed solid advantages over Medtronic’s Resolute Onyx Drug-Eluting Stent.

• Lp(a) and OxPL’s HF Impact: A new AHA study suggests that high Lp(a) and oxidized phospholipid (OxPL) levels are linked to greater heart failure progression. The researchers followed 714 individuals with stage A/B HF for an average of 3.7 years, finding that participants with Lp(a) ≥150 nmol/L had far higher risk for progression to symptomatic HF (HR: 1.90) or the composite of HF/cardiovascular death (HR: 1.71). Higher OxPL was similarly associated with HF progression risk, particularly when added to higher Lp(a).

• Elutia EluPro’s FDA: The Elutia EluPro BioEnvelope just became the first FDA-cleared antibiotic-eluting biologic envelope, used to avoid infection following cardiac pacemaker and defibrillator implantations. EluPro features embedded antibiotics (rifampin and minocycline) that are released over an extended period combined with a “natural extracellular tissue matrix” to create a “BioEnvelope” that over time regenerates into a protective pocket of a patient’s own tissue. 

• Novice Echo AI for Heart Failure: The combination of Us2.ai’s echo AI software and EchoNous’ handheld ultrasound enabled novice healthcare professionals to perform point-of-care heart failure screening, with good results. In a paper in Nature Scientific Reports (and originally presented at ACC 2023), researchers in the PANES-HF trial found that novices with no echo AI experience who scanned 96 symptomatic patients had good performance (AUC=0.88), sensitivity (85%), specificity (91%), and positive (79%) and negative (94%) predictive values. 

• Predicting Cardiac Arrests: University of Washington researchers found that common EHR data can be used to identify people with higher risks of suffering out-of-hospital cardiac arrests (OHCAs). The researchers analyzed EHR data from 2,366 individuals with OHCA and 23,660 matched controls, finding significant differences in the OHCA group (longer QT interval, substance abuse, fluid and electrolyte disorder, higher heart rate). The EHR machine learning models identified OHCA individuals far more accurately than a model based on cardiovascular risk factors (AUROC: 0.80-0.85 vs. 0.66).

• CVAUSA Adds athenahealth: Major private equity-owned cardiology MSO Cardiovascular Associates of America selected athenahealth as its practices’ go-to health IT platform. The alliance gives CVAUSA’s 23 practices preferred status to purchase athenaOne, athenahealth’s suite of EHR, revenue cycle management, and patient engagement solutions. Given that more than half of CVAUSA’s practices were acquired in the last 18 months, the athenahealth partnership might be a key step in bringing these practices under a unified platform.

• Heat’s Heart Attack Risks: A small laboratory-based study showed that as body temperature increases, so does the risk for myocardial ischemia. In the study of 61 participants, a 1.5 degree Celsius rise in core temperature increased myocardial blood flow by 208% in healthy young adults, 179% in healthy older adults, and by 164% among older adults with CAD. Even scarier, seven out of 20 patients in the CAD group had imaging evidence of asymptomatic heat-induced myocardial ischemia.

• Impella’s RECOVER IV Halted: The RECOVER IV trial evaluating Abiomed’s Impella pump has been halted, now that the previous DanGer Shock trial demonstrated that the Impella pump actually does save lives during STEMI and cardiogenic shock. The decision came from RECOVER IV’s data and safety monitoring board, likely due to the ethical issues of continuing a randomized trial on a device that’s proven to work on these extremely sick patients.

• Fortune 42: Healthcare had a strong showing in this year’s Fortune 500, with 42 medical companies included in the list of businesses with the most annual revenue across all industries. UnitedHealth Group scored healthcare’s top spot at five overall, followed by fourteen pharma companies (starting with Pfizer at rank 38), five for-profit health systems (HCA ranked highest at 66), and six device manufacturers (Abbott was highest at 99). Other notable cardiology-focused companies included J&J, BMS, Merck, Amgen, Regeneron, Boston Scientific, Medtronic, and Cardinal Health.

Monebo’s AF ECG Algorithm

Atrial fibrillation is often difficult to characterize with an automated algorithm due to the changing waveform morphology, system, or muscle noise. This is especially true given the size constraints of ambulatory devices to detect AFib. See how Monebo’s Kinetic AF ECG Algorithm overcomes these size limitations without sacrificing accuracy.

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

The Resource Wire

• Where to Go for Cardio AI? TeraRecon’s Cardio Suite is a collection of hand-selected, vendor-neutral Cardiology AI algorithms that aid in the analysis and interpretation of echocardiograms and chest CTs. Learn about TeraRecon’s AI offering and how they improve efficiency and accuracy here.

• AI-Driven Novice Heart Failure Screening: We hear a lot about AI’s potential to expand echocardiography to far more users and clinical settings, and a study using Us2.ai’s AI-automated echo analysis and reporting solution showed that echo AI might make novice-led heart failure screening possible.

• Forging the Future of Cardiovascular Care: Cardiology is changing, and for the better. Get a view into Lee Health Heart Institute’s medical director Richard Chazal, MD’s vision for a new era in cardiology, driven by imaging, AI and personalized medicine.

• 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.