Month: February 2023

LDL-TG’s Atherosclerosis Association

Posted on by Madeline Kane

Out of tens of thousands of blood-based molecules and biomarkers, triglyceride-rich LDL molecules (LDL-TG) emerged as a direct cause of atherosclerotic coronary artery disease (ASCAD). 

LDL-C and Apo-B are widely known CVD risk factors, but it’s still unclear which specific risk factors underlie atherosclerosis, and to what extent. To investigate this, the authors applied a hypothesis-free Bayesian network analysis and genetic studies to 665 patients with suspected CAD.

The authors assessed simultaneous associations between genotypes, gene expression levels, circulating biomarkers, and CT-based atherosclerosis levels, finding that… 

  • LDL-TG was directly upstream from atherosclerosis in the Bayesian analysis.
  • LDL-TG was associated with atherosclerosis independent of well-known factors like age, sex, LDL-C and ApoB levels.
  • Genetic variations that “turned off” the hepatic lipase gene correlated with LDL-TG levels and atherosclerosis.
  • LDL-TG was positively linked to triglycerides, sd-LDL, and inflammatory markers.

What’s new? These findings are consistent with previous literature, but also reveal that LDL-TG has a central causal role in ASCAD, potentially as a result of abnormal hepatic lipase activity.  

The Takeaway 

The study suggests that triglyceride-rich LDL particles directly cause atherosclerotic CAD. With the recent introduction of a simple and fully automated method to measure LDL-TG levels, this biomarker may become an important tool in the clinical assessment of atherosclerosis. 

The analysis also showcases a promising new approach to evaluate genetic predisposition to ASCAD, and demonstrates how big “omics” data combined with AI has the potential to reveal novel treatment avenues.

Uncovering the Long-Term CV Risks Following Pregnancy Complications

Posted on by Madeline Kane

A Swedish cohort study found that approximately 30% of pregnant women have a major pregnancy complication, which can lead to an elevated risk for ischemic heart disease that persists for decades.

Using data from 2.1M Swedish women, the authors examined five major types of adverse pregnancy outcomes: preterm delivery (< 37 weeks gestation), small for gestational age, preeclampsia, other hypertensive disorders of pregnancy, and gestational diabetes.

Women with one (or more) adverse pregnancy events had increased risk for CAD out to 46 years post-pregnancy.  

  • Over the follow-up period (median 25 years, maximum 46 years), 3.8% of women were diagnosed with ischemic heart disease.
  • 10 years postpartum, those who had pregnancy-related hypertensive disorders had the greatest CAD risk (adjusted HR 2.09), followed by those with preterm delivery (HR 1.72), preeclampsia (HR 1.54), gestational diabetes (HR 1.30), and a small-for-gestational-age infant (HR 1.10).
  • 10-19 years postpartum, having a small-for-gestational-age infant was associated with the highest CAD risk.
  • 20-29 years postpartum, gestational diabetes was associated with the highest risk.
  • 30-46 years postpartum, adjusted hazard ratios for CAD decreased but remained elevated compared with those without adverse pregnancy outcomes. 

The Takeaway

Long-term risks of pregnancy complications often go unmentioned between women and their physicians in routine practice. But this study reveals that adverse pregnancy outcomes are important lifelong risk factors for heart disease, and provide an opportunity to identify high-risk women earlier than with traditional risk factors alone. 

GE HealthCare Adds Echo Guidance with Caption Health Acquisition

Posted on by Madeline Kane

GE HealthCare took a major step towards expanding echo ultrasound exams to new users and settings, acquiring AI guidance startup Caption Health.

GE plans to integrate Caption’s AI guidance technology into its point-of-care ultrasound platform, specifically emphasizing how Caption’s tech will help streamline echo adoption among novice operators and bring heart failure exams into “doctors’ offices, the home, and alternate sites of care.”

  • That’s particularly notable given healthcare’s major shift outside of hospital walls, and the continued challenges with sonographer staffing levels.
  • That strategy is also helped by the fact that Caption already operates a unique home echo exam and virtual diagnosis service through partnerships with Portamedic and HeartBeat Health. 

GE didn’t disclose the tuck-in acquisition’s value, but Caption is relatively large for an imaging AI startup (79 employees on LinkedIn, >$62M raised) and is arguably the most established company in the ultrasound guidance segment (FDA & CE approved, CMS-reimbursed, notable alliances).

However, there’s still a sizable group of startups focusing on making echo exams easier and more accessible, including AI companies developing similar echo image acquisition guidance tools or creating AI solutions that automate echo measurements and reporting.

The acquisition is also another sign that the imaging AI consolidation trend remains in full swing, marking at least the ninth AI startup acquisition since January 2022 and the third so far in 2023. That consolidation has largely steered clear of cardiology-related AI startups before now, but it’s worth noting that this is the second AI guidance startup to be acquired by an ultrasound manufacturer in the last six months.

The Takeaway

Echo’s potential expansion to new users and clinical settings could create the kind of growth that most exams only experience once in their lifetime (or never experience), and ease of use will likely dictate how far echo is able to expand. That could make this acquisition particularly significant for GE HealthCare and for echo’s path towards far broader adoption.

Biosense Webster’s PFA Milestone

Posted on by Madeline Kane

J&J’s Biosense Webster subsidiary is making strides toward the completion of its pulsed field ablation (PFA) clinical trial, joining competitors Medtronic and Boston Scientific in the race for FDA approval. 

PFA devices deliver short electrical pulses to scar tissue in the heart and interrupt irregular electrical pathways that cause AFib. The new approach has gained attention among electrophysiologists because it causes less tissue damage than the current standard ablation procedures.  

The analysis, dubbed inspIRE, evaluated Biosense Webster’s PFA system among 226 patients with drug-refractory paroxysmal AFib (40 in wave I and 186 in wave II).

Here are key findings from during the procedure:  

  • Entrance block was achieved in 100% of patients.
  • PVI without reconnection was achieved in 96-97% of target veins. 
  • Mean procedure time declined from 82.4 minutes in wave I to 70.1 minutes in wave II. 

At one year, the researchers found: 

  • 71% of patients experienced no atrial arrhythmia (above the performance goal of 50%)
  • 0% of patients experienced procedure-related safety events 

The Takeaway

Pulsed field ablation has had tremendous commercial success in Europe, and now medtech companies are vying to establish their product as effective and be the first to the US market. Biosense Webster’s inspIRE trial was the latest of the three companies to report clinical trial progress and suggests that PFA FDA approval is on the horizon.

Challenging the HFpEF Treatment Dogma

Posted on by Madeline Kane

The landmark myPACE trial found that patients with HFpEF who have their pacemakers’ set to a higher backup resting heart rate reaped important health benefits. The findings challenge the long-standing belief among cardiologists that patients with HFpEF and diastolic dysfunction benefit from lower heart rates.  

The authors screened 1,500 patients with HFpEF and randomly assigned 107 of them to receive either standard pacing at 60 bpm or a higher rate based on age, height, and ejection fraction. The screening process was so selective because they only included those with existing pacemakers that allowed the researchers to increase the heart rate without exacerbating RV dyssynchrony. 

At one year, the personalized accelerated pacing led to improvements in… 

  • NT-proBNP levels (-109 pg/dL vs. +128 pg/dL) 
  • Physical activity levels (+47 minutes/day vs. -22 minutes/day)
  • AFib (27% relative risk reduction) 

The Takeaway
The study rewrites the long-held view that lower pacing is better for people with HFpEF. Of course, this is just one, small RCT, and larger scale studies are necessary to confirm the findings. Interestingly, the findings do align with a 2021 study that found that beta blocker withdrawal in HFpEF patients improved maximal functional capacity.

The Power of Low Lifelong LDL-C

Posted on by Madeline Kane

A high-impact genetic association study found that people with certain genetic variants were 50% less likely to develop coronary heart disease. The findings reveal the importance of maintaining low LDL-C (or “bad” cholesterol) levels over a lifetime.

Pharmacological LDL-C management may reduce the risk of developing CHD by 22%, but this study found that people who had variations in either APOB or PCSK9 (two genes known to be associated with LDL-C) were even more protected against CHD. 

The authors combined genetic and clinical data from more than 200,000 participants from 5 NHLBI prospective cohorts and the UK Biobank. Of these, 139 (0.7%) carried a truncating mutation in either APOB or PCSK9–switching these genes off. 

Over a median of 21.5 years…

  • A CHD event (like a heart attack or death) was far less likely in APOB or PCSK9 variation carriers than noncarriers (8.6% vs. 16%), corresponding to a 49% reduced CHD risk (HR: 0.51). 
  • Carriers had a 45 to 49 mg/dL lower average untreated LDL-C level. 

To put the magnitude of the 49% reduced CHD risk into perspective, here is how traditional risk factors affected the likelihood of developing CHD. 

  • No diabetes reduced risk by 53%
  • No hypertension reduced risk by 25%
  • Not smoking reduced risk by 43%. 

That’s right: a APOB or PCSK9 variation carrier who smokes is more protected against CHD than a noncarrier who does not smoke. 

The Takeaway
Analysis of DNA variants that turn off APOB or PCSK9 revealed the power of lifelong low LDL-C. For LDL, it’s not only about how low the levels are, but for how long those levels have stayed low.

Echo AI Model for CAC Scoring

Posted on by Madeline Kane

A Cedars-Sinai-led team developed an echocardiography AI model that accurately assessed coronary artery calcium buildup, potentially revealing a safer, more economical, and more accessible approach to CAC scoring.

The researchers used 1,635 Cedars-Sinai patients’ transthoracic echocardiogram (TTE) videos paired with their CT-based Agatston CAC scores to train an AI model to predict patients’ CAC scores based on their PLAX view TTE videos. 

When tested against Cedars-Sinai TTEs that weren’t used for AI training, the TTE CAC AI model detected…

  • Zero CAC patients with “high discriminatory abilities” (AUC: 0.81)
  • Intermediate patients “modestly well” (≥200 scores; AUC: 0.75)
  • High CAC patients “modestly well” (≥400 scores; AUC: 0.74)

When validated against 92 TTEs from an external Stanford dataset, the AI model similarly predicted which patients had zero and high CAC scores (AUCs: 0.75 & 0.85).

More importantly, the TTE AI CAC scores accurately predicted patients’ future risks. TTE CAC scores predicted one-year mortality similarly to CT CAC scores, and they even improved overall prediction of low-risk patients by downgrading patients who had high CT CAC scores and zero TTE CAC scores.

The Takeaway

CT-based CAC scoring is widely accepted, but it isn’t accessible to many patients, and concerns about its safety and value (cost, radiation, incidentals) have kept the USPSTF from formally recommending it for coronary artery disease surveillance. We’d need a lot more research and AI development efforts, but if TTE CAC AI solutions like this prove to be reliable, it could make CAC scoring far more accessible and potentially even more accepted.

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