The Renaissance in Lipid Lowering Therapies - Abstract Coming Soon!

Pamela Bowie Morris, MD, FACC, FAHA, FASPC, FESC, FNLA

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Atrial Myopathy – A New Target for Stroke and Dementia Prevention

Lin Yee Chen, MBBS, MS

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Atrial myopathy—characterized by alterations in left atrial function and structure—is a novel and independent risk factor for cardiovascular outcomes such as atrial fibrillation (AF), heart failure, and sudden cardiac death. More recently, atrial myopathy has been shown to be an independent risk factor for neurocognitive outcomes such as ischemic stroke and dementia. Importantly, atrial myopathy has been shown to confound the relationship of AF to neurocognitive outcomes such as ischemic stroke and dementia, raising the key question whether AF is actually an independent risk factor for the foregoing neurocognitive outcomes. Moreover, consideration of atrial myopathy can enhance risk prediction of ischemic stroke in patients with AF, thus refining the use of oral anticoagulation. Finally, the time is ripe for a clinical trial to test the hypothesis that in people with embolic stroke of undetermined source and atrial myopathy, anticoagulation can prevent recurrent ischemic stroke and dementia.

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Primum non nocere, secundum cavere, tertium sanare: Reaping the benefits while balancing radiation risks of cardiac imaging
Andrew Einstein, MD PhD

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​Developments in imaging have profoundly reshaped the landscape of cardiovascular care in the past few decades and improved outcomes for innumerable patients.  Each imaging modality has a unique profile of potential virtues for diagnosis, prognosis, and guidance of therapy.  At the same time, each has potential downsides, ranging from overtreatment and undertreatment, to kidney failure, to serious reactions to the drugs we use as part of imaging. Much of my research has focused on characterizing and reducing the burden of ionizing radiation from cardiac imaging.  Patients receive radiation from nuclear cardiology, cardiac CT, and fluoroscopy, and this radiation has been estimated to account for a fifth of all nontherapeutic radiation to Americans and thousands of cancers per year.  Nevertheless, it is a subject which has been hampered by both partisan downplay and intellectual dishonesty on the one hand, and sensationalism on the other.  In this talk, I’ll provide background on the growth and evolution of cardiac imaging, how we characterize and estimate radiation doses, and some epidemiological and biophysical data linking ionizing radiation to patient risks.  We’ll cover in some detail observational studies describing radiation dose to patients from nuclear cardiology and cardiac CT, with a focus on the IAEA Noninvasive Cardiology Protocols Study (INCAPS) 4, which we first presented at ESC 2025.  This study, conducted at 747 sites in 101 countries ranging from the US, UK, and Japan to Nicaragua, Burkina Faso, and Fiji, found remarkable variation in radiation doses and use of best practices across the globe. Radiation doses varied significantly between tests, centers, countries, and income levels. This was especially pronounced for coronary CTA, where median dose in low- and lower-middle income countries was >280% that in high-income countries, and median dose in Africa >500% that in Western Europe. Simultaneously, within income levels and world regions, marked variation was observed.  We’ll close with a discussion of opportunities to reduce and standardize radiation exposures from cardiac testing, including worldwide implementation of best practices.

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Clinical Presentation of End-Stage Atrial Myopathy in Longstanding Persistent or Permanent Atrial Fibrillation

​Jose Joglar, MD

​​Authors: Frans Serpa, MD; Nimesh Patel, MD; Jose A. Joglar, MD

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Background: Long-standing persistent or permanent atrial fibrillation (AF) can cause progressive atrial fibrosis, ultimately rendering the atrium electrically and mechanically inactive. This process can replace AF with alternative atrial rhythms, including atrial standstill. Recognizing this advanced atrial myopathy is crucial for clinical decision-making.

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Objective: To describe the clinical presentation of end-stage atrial myopathy in patients with longstanding AF. We characterized a spectrum of findings, including loss of fibrillatory wave amplitude, atrial standstill with junctional rhythms, and low-amplitude atrial tachycardias resistant to ablation.

Methods: We conducted a retrospective case series of seven patients with longstanding persistent AF and advanced atrial myopathy, analyzing ECGs, device interrogations, and electrophysiology (EP) study data.

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Results: We identified seven patients (mean age 69 ± 14 years, 71% men) with long-standing persistent AF and multiple cardiometabolic comorbidities. Clinical presentations fell into three main categories. Four patients progressed from AF to atrial standstill with junctional rhythms (Figure 1A), confirmed by loss of fibrillatory waves on ECG and, in two cases, absent atrial capture and sensing on device interrogation (Figure 1B). Two patients presented with very low-amplitude atrial tachycardias (Figure 1C); one had multiple tachycardias and extensive fibrosis during an unsuccessful ablation. The final patient showed a transition from AF to AF with a competing junctional rhythm, possibly representing an intermediate stage.

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Conclusion: End-stage atrial myopathy, resulting from extensive fibrosis in long-standing AF, presents as a spectrum of rhythms, including atrial standstill with junctional rhythms and low-amplitude atrial tachycardias. These findings are often corroborated by absent atrial sensing/capture on device interrogation or extensive fibrosis on EP study. Recognition is critical to better tailor therapies, as these patients are typically poor candidates for AF ablation or atrial pacing.

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Using the Blood Donation System as Novel Strategy for Detection and Treatment of Familial Hypercholesterolemia

Amit Khera, MD, MSc, FACC, FAHA, MASPC

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Background: Familial Hypercholesterolemia (FH) is an autosomal dominant disorder resulting in very high low density lipoprotein cholesterol (LDL-C) from birth and up to a 15-fold increased risk of coronary artery disease.  Despite cheap and effective treatments, FH remains significantly underdiagnosed and undertreated.  Approximately 7 million people donate blood in the US every year with many blood donation centers performing total cholesterol screening at no charge, providing a readily available opportunity to diagnose FH.

 

Methods: This study analyzed deidentified data from Carter BloodCare donors aged ≥16 years between 2002 and 2016. Carter BloodCare, serving ~8 million people in Texas, routinely measures nonfasting serum cholesterol during donor screening. Data were examined from October 2017 to March 2019. Familial hypercholesterolemia was defined using Make Early Diagnosis to Prevent Early Death (MEDPED) criteria, applying age-specific cholesterol thresholds: ≥270 mg/dL (<20 years), ≥290 mg/dL (20–29 years), ≥340 mg/dL (30–39 years), and ≥360 mg/dL (≥40 years). For donors with multiple visits, the highest recorded cholesterol value was used in analyses to identify FH prevalence. Based on the results of this study, the The Blood DONor Awareness and TrEatment of Familial Hypercholesterolemia (DONATE-FH) trial was launched.

 

Results: The study included 1,178,102 individual donors with a total of 3,038,420 blood donations. Of all individual donors (median total cholesterol level, 183 [interquartile range (IQR), 157-212] mg/dL; median age, 32 [IQR, 19-47] years; 619 583 [52.6%] women), a total of 3473 individuals (or 1 in every 339) met criteria for FH, which is similar to the prevalence in the general population. This group had a median (IQR) total cholesterol of 332 (297-377) mg/dL. Estimated prevalence was higher at younger ages (<30 years: 1:257) compared with older ages (≥30 years: 1:469; P < .001) and in men (1:327) compared with women (1:351; P = .03).  Using the findings from this study, we launched the DONATE-FH trial which is a hybrid type 2 effectiveness-implementation study conducted at Carter BloodCare in Texas. Phase I employed mixed-methods guided by the Consolidated Framework for Implementation Research and Implementation Mapping to identify barriers and facilitators of LDL-C treatment among blood donors with FH (n=25), PCPs (n=7), and staff (N=8). Based on qualitative interviews, an implementation strategy bundle was developed including donor notification, educational materials, care navigation, and physician resources. Phase II is a randomized trial comparing this bundle to usual care, with primary outcome of LDL-C reduction at six months.  To date, 75 of an anticipated 100 donors with FH have been enrolled.  The characteristics of enrolled population include mean age 43.4 years, 56% female, 80% white race, mean baseline total cholesterol 326.0 mg/dl (±53.0) and LDL-C 214.2 (±51.6).

 

Conclusions: The prevalence of FH in a large cohort of blood donors was similar to the estimated prevalence of this disorder in the general population. The blood donor screening program could be a novel strategy to detect and implement treatment for individuals with potential FH, particularly younger individuals in whom early detection and treatment is especially important.  The ongoing DONATE-FH trial may establish a novel paradigm for treatment of FH that involves partnership with the community blood donor system, with the intent to rapidly scale this program to the large number of community-based blood centers throughout the country, having an immediate impact on gaps in FH care.

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Transthyretin Cardiac Amyloidosis - Transition from a Rare and Underrecognized Condition to a Commonly Encountered and Treatable Disorder

Mathew Mauer, MD

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Dr. Maurer research focused on transthyretin cardiac amyloidosis (ATTR=CA). He and colleagues have demonstrated that technetium-based isotopes employed for >50 years in nuclear medicine for bone imaging can be repurposed for the non-invasive diagnosis of ATTR cardiac amyloidosis replacing an endomyocardial biopsy. Using this technique, ATTR-CA has been demonstrated to be prevalent in patients with heart failure, severe aortic stenosis, in those with carpal tunnel syndrome and with a hypertrophic cardiomyopathy phenotype. Leveraging data from national and international registries, he elucidated genotype-phenotype relationship and has focused on underrepresented minorities who have West African ancestry and harbor a variant in TTR that is present in >1.5 million Black Americans. He has won awards for his mentorship of the next generation of clinical researchers from NIA and Columbia University, fostering the careers of numerous faculty from diverse backgrounds. Finally, he spearheaded drug development in the arena, being the Chair of the Steering Committee for the ATTR-ACT trial, which demonstrated the efficacy of tafamidis, a TTR stabilizer and Helios-B, which demonstrated the efficacy of vutrisiran, a TTR gene silencer. Collectively, his research changes the diagnostic and therapeutic landscape for cardiac amyloidosis. A disease that formerly was conceived as uncommon and untreatable is now increasingly recognized with available therapies that dramatically extend survival and mitigate symptoms. Advances in noninvasive diagnosis coupled with concurrent demonstration of efficacy and approval of specific therapies has shifted cardiac amyloidosis from a rarely encountered and untreatable “zebra,” to a condition that cardiovascular clinicians now consider in daily practice.

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Climate Change, Environmental Pollution and Health: A Story of Unintended Consequences, Complexity,

Regime Change and Geopolitical Context

Sanjay Rajagopalan, MD, MBA, FAHA, FACC

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Climate change and environmental pollution have become defining health challenges of the 21st century, exerting profound effects through pathways that are interconnected, nonlinear, and shaped by global systems of energy, economics, and policy. Cardiovascular disease—already the leading cause of death worldwide sits at the center of this evolving landscape. This presentation reframes climate change and pollution as core determinants of cardiovascular health, emerging from a complex adaptive system in which unintended
consequences, mathematical feedback loops, and geopolitical pressures interact to influence exposure and disease risk. Understanding these developments through the lens of complexity science helps explain why seemingly small policy changes can have outsized health impacts. Pollution and climate systems exhibit threshold effects, reinforcing feedback loops, and nonlinear dynamics that make reversal increasingly difficult once degradation accelerates. At the same time, geopolitical factors, energy insecurity, supply-chain fragility,
and competition for strategic minerals shape national decisions around fossil fuels and renewable technologies, further influencing exposure patterns and health trajectories.

Combustion processes responsible for rising carbon dioxide levels also generate fine particulate matter (PM₂.₅), nitrogen oxides, volatile organic compounds, and toxic aerosols. Though CO₂ persists in the atmosphere for centuries and PM₂.₅ for days, their biological impacts converge on shared mechanisms: oxidative stress, endothelial dysfunction, autonomic imbalance, systemic inflammation, and heightened
arrhythmia susceptibility. Advances in satellite-based exposure assessment and atmospheric modeling have strengthened the evidence linking small increases in PM₂.₅ with higher rates of myocardial infarction, stroke, heart failure, arrhythmias, and all-cause mortality. At population scales, the cardiovascular burden attributable to pollution rivals or exceeds that of many traditional risk factors.

Despite these scientific advances, recent U.S. policy decisions have weakened environmental protections at a critical moment. Air pollution levels have gone up on account of wildfires and are on an incremental arc, thanks to relaxation of automobile emissions standards, expansion of fossil fuel extraction, and delays in transitioning heavy industry toward cleaner alternatives. Transportation remains a dominant source of greenhouse gases and loosening emissions standards will disproportionately harm already vulnerable communities. Based on established exposure–response functions, even small increases in ambient particulate levels are expected to result in thousands of additional preventable cardiovascular deaths.

The health care sector itself contributes 8–10% of U.S. carbon emissions, with hospitals representing some of the most energy-intensive facilities in the economy. This places cardiology in a dual position: affected by climate change yet also implicated in driving it. Embedding sustainability into cardiovascular care offers an opportunity to reduce emissions while improving efficiency and decreasing costs. Sustainability should be recognized as a central principle of preventive cardiology, preventing exposure, preventing disease, and
preventing unnecessary resource consumption.

This presentation argues that climate change and environmental pollution constitute the next frontier of cardiovascular prevention. Cardiologists must engage these issues not as peripheral concerns but as integral to our mission to improve population health. Addressing the convergence of climate, pollution, complexity, and geopolitics will require reframing prevention, advocating for science-based policy, and embracing sustainability as a clinical and institutional priority. In doing so, we can help shape a more resilient and health-promoting future.

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LDL Cholesterol: Lowest for Longest is Best Across the Spectrum of Risk

Marc Sabatine, MD, MHP

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Early randomized, placebo-controlled, cardiovascular outcomes trials, such as the 4S trial, demonstrated the clinical benefit of statins in patients with a prior myocardial infarction and very high LDL cholesterol levels. Subsequent trials, such as the CARE trial, challenged the notion that we should accept so-called “average” LDL cholesterol levels in patients with a prior myocardial infarction. These trials showed lower rates of major adverse cardiovascular events when LDL cholesterol levels were decreased with statin therapy from ~140 mg/dL to ~100 mg/dL. Based on these data cholesterol treatment guidelines recommended an LDL cholesterol goal of <100 mg/dL in patients with coronary heart disease. PROVE IT – TIMI 22 was the first trial to demonstrate the clinical benefit of high- vs. moderate-intensity statin therapy in patients with a recent acute coronary syndrome. The high-intensity statin arm achieved an LDL-C of 62 mg/dL, and on that basis the cholesterol guidelines adopted a target of <70 mg/dL in very high-risk patients.

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The first cardiovascular outcomes trial demonstrating the clinical benefit of adding a nonstatin to a statin was IMPROVE IT (TIMI 40). Ezetimibe reduced LDL cholesterol by 24% from 70 mg/dL to 54 mg/dL and reduced the risk of major adverse cardiovascular events in patients with a recent acute coronary syndrome.

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The advent of PCSK9 inhibitors permitted the testing of even more potent nonstatin therapy. In the FOURIER (TIMI 59) trial, we demonstrated that in patients with a prior major atherosclerotic cardiovascular disease event, the additional of evolocumab to statin therapy reduced LDL-C levels by 59% down to a median of 30 mg/dL and, over a median of just 2.2 years of follow-up, reduced the risk of major adverse cardiovascular events by 15-20%.

Most recently, in the VESALIUS-CV (TIMI 66) trial, we investigated the benefit of adding evolocumab to statin therapy in patients with atherosclerosis or diabetes, but without a prior myocardial infarction or stroke. The goal was to see whether intensive therapy could prevent a first major atherosclerotic cardiovascular disease event. Evolocumab lowered LDL cholesterol levels by 55% down to a median of 45 mg/dL. Over a median of 4.6 years of follow-up, evolocumab reduced the risk of major adverse cardiovascular events by 25%. There was also a nominally lower rate of all-cause mortality. Results were consistent across subgroups, including patients with diabetes and no qualifying atherosclerosis.

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Current dyslipidemia guidelines recommend LDL cholesterol goals of under 55 to 70 mg/dL in very high-risk patients and to consider a goal of under 40 mg/dL only in patients with recurrent events or polyvascular disease. The findings from FOURIER and VESALIUS-CV support more intensive LDL cholesterol lowering down to ~40 mg/dL in patients across the entire spectrum of atherosclerotic cardiovascular disease and in patients at high risk for atherosclerosis.