Daily Cardiology Research Analysis
A randomized trial (CENTURY) showed that an intensive lifestyle-plus-medical program with PET coronary flow capacity guidance reduced death, myocardial infarction, and revascularization in chronic coronary disease. Mechanistic imaging from PROSPECT II linked elevated lipoprotein(a) specifically to focal vulnerable coronary plaques, distinct from LDL-related diffuse atherosclerosis. In Medicare patients >60 years, PFO closure lowered recurrent ischemic stroke versus medical therapy, albeit with s
Summary
A randomized trial (CENTURY) showed that an intensive lifestyle-plus-medical program with PET coronary flow capacity guidance reduced death, myocardial infarction, and revascularization in chronic coronary disease. Mechanistic imaging from PROSPECT II linked elevated lipoprotein(a) specifically to focal vulnerable coronary plaques, distinct from LDL-related diffuse atherosclerosis. In Medicare patients >60 years, PFO closure lowered recurrent ischemic stroke versus medical therapy, albeit with slightly higher early AF/VTE risks.
Research Themes
- Physiology-guided comprehensive management in stable coronary artery disease
- Lipoprotein(a) as a driver of focal vulnerable plaque formation
- Stroke prevention strategies in older patients with patent foramen ovale
Selected Articles
1. Optimal medical care and coronary flow capacity-guided myocardial revascularization vs usual care for chronic coronary artery disease: the CENTURY trial.
In this randomized trial (n=1,028), a comprehensive PET–coronary flow capacity–guided program combining intensive lifestyle modification and aggressive goal-directed medical therapy reduced 11-year all-cause mortality, death/MI, late revascularization, and MACE compared with usual care. Revascularization within 90 days was rare and predominantly reserved for severely reduced CFC.
Impact: It provides randomized evidence that physiology-guided comprehensive care changes hard outcomes over a decade in chronic CAD, supporting a shift toward integrated, goal-based management with selective revascularization.
Clinical Implications: Adopt integrated programs that combine intensive lifestyle intervention and goal-directed pharmacotherapy with PET-based CFC to triage revascularization, aiming to reduce mortality and MI in stable CAD.
Key Findings
- Comprehensive care lowered 11-year all-cause mortality (4.7% vs 8.2%; P=0.023).
- Death or MI was reduced (7.0% vs 11.1%; P=0.024) and late revascularization decreased (9.5% vs 14.8%; P=0.021).
- Major adverse cardiac events were significantly lower (20.5% vs 29.9%; P=0.0006).
- Only 5.4% underwent early revascularization, predominantly guided by severely reduced CFC.
Methodological Strengths
- Randomized design with long-term (up to 11 years) outcomes and repeated PET physiology.
- Comprehensive, protocolized intervention with clear CFC-based revascularization criteria.
Limitations
- Single-center programmatic model may limit generalizability across health systems.
- Open-label comprehensive care with frequent contacts may introduce performance bias.
Future Directions: Multicenter pragmatic trials to test PET-CFC–guided comprehensive care pathways, cost-effectiveness analyses, and implementation frameworks across diverse healthcare settings.
2. Lipoprotein(a), Cholesterol, Triglyceride Levels, and Vulnerable Coronary Plaques: A PROSPECT II Substudy.
In 865 recent MI patients with 3-vessel NIRS–IVUS imaging, TC, LDL-C, and non-HDL-C tracked pancoronary plaque and lipid burden, whereas Lp(a) uniquely associated with focal vulnerable plaques. This mechanistic distinction provides a rationale for Lp(a)-targeted therapies to reduce MI risk by addressing plaque vulnerability.
Impact: It clarifies that Lp(a) is linked to focal plaque vulnerability rather than diffuse plaque burden, refining pathophysiologic understanding and informing targeted Lp(a)-lowering strategies.
Clinical Implications: Beyond LDL-C lowering for diffuse atherosclerosis, consider Lp(a) assessment to identify patients at risk for focal vulnerability who may benefit from emerging Lp(a)-lowering therapies.
Key Findings
- TC, LDL-C, and non-HDL-C associated with pancoronary plaque volume and lipid core burden (P<0.01).
- Lp(a) was independently associated with focal vulnerable plaques (P=0.01), not with diffuse plaque burden.
- HDL-C and triglycerides were not highlighted as drivers of focal vulnerability in multivariable models.
Methodological Strengths
- Three-vessel, coregistered NIRS–IVUS imaging after culprit treatment enabling whole-coronary assessment.
- Rigorous multivariable analyses defining focal vulnerable plaque by standardized thresholds.
Limitations
- Observational, post-MI cohort; causality cannot be inferred and selection bias possible.
- Single baseline lipid/lipoprotein measurements; generalizability beyond recent MI populations is uncertain.
Future Directions: Prospective studies linking Lp(a) lowering to reduction in imaging-defined vulnerable plaques and clinical MI, and integration with CT/NIRS-IVUS risk modeling.
3. PFO Device Closure in Patients >60 Years of Age With Ischemic Stroke: Results From U.S. Medicare Beneficiaries.
In Medicare beneficiaries >60 years with ischemic stroke and PFO/ASD, propensity-matched analysis showed PFO closure reduced recurrent ischemic stroke (HR 0.62) compared with medical therapy, with acceptable safety but higher early venous thromboembolism and atrial fibrillation/flutter.
Impact: Expands real-world evidence supporting PFO closure beyond age 60, a population not addressed by prior RCTs, with implications for guideline refinement and shared decision-making.
Clinical Implications: For selected older patients with ischemic stroke and PFO, device closure may be considered to reduce recurrent stroke, with counseling on early AF/VTE risks and post-procedure monitoring.
Key Findings
- PFO closure reduced recurrent ischemic stroke vs medical therapy (HR 0.62; P=0.007).
- No difference in 30-day mortality; higher VTE (1.86% vs 0.37%) and AF/flutter (1.41% vs 0.64%) after closure.
- Median follow-up 2.58 years in a matched cohort of 5,508 beneficiaries (median age 71).
Methodological Strengths
- Large, national Medicare cohort with device registry linkage and 1:4 propensity score matching.
- Evaluation of both efficacy (recurrent stroke) and 30-day safety endpoints.
Limitations
- Observational design with potential residual confounding and selection bias.
- Generalizability limited to U.S. Medicare population; device-specific effects not randomized.
Future Directions: Prospective studies or pragmatic trials in older patients, optimized antithrombotic strategies post-closure, and risk models to balance stroke reduction vs AF/VTE.