Leandro Slipczuk

Background: The incremental prognostic value of regional myocardial flow reserve (MFR) assessed by positron emission tomography (PET) myocardial perfusion imaging (MPI) beyond global MFR remains unclear. We sought to evaluate the prognostic value of regional MFR in the international multicenter REFINE PET registry. Methods: This retrospective multicenter cohort study included 35,391 patients from 13 sites in the international REFINE PET registry who underwent rubidium-82 ( ⁸² Rb) and ¹³ N-ammonia ( ¹³ NH ₃ ) PET MPI. Abnormal MFR was defined as 90 days), and hospital admission for unstable angina. Results: During a mean follow-up of 4.0 ± 2.9 years, 9,903 patients (28.0%) experienced MACE. Annualized MACE rates increased stepwise across MFR-Groups 1-3 (4.0%/year, 7.5%/year, and 11.8%/year, respectively; p p p p <0.001). Conclusions: Regional MFR provided incremental prognostic value beyond conventional PET MPI findings, including global MFR, and may refine risk stratification, particularly when global MFR is preserved. Clinical perspectives: Global myocardial flow reserve (MFR) is widely used for risk stratification in patients undergoing positron emission tomography (PET) myocardial perfusion imaging (MPI). However, regional abnormalities in MFR may be overlooked when global MFR is preserved. In this international multicenter study of 35,391 patients, abnormal regional MFR was independently associated with major adverse cardiovascular events and provided incremental prognostic value beyond conventional clinical and PET-MPI findings, including global MFR and myocardial perfusion abnormalities. Importantly, even among patients with normal perfusion and preserved global MFR, those with abnormal regional MFR had a substantially higher annualized event rate than those with normal regional MFR (5.0% versus 2.8%). These findings highlight the importance of assessing regional MFR in addition to global MFR during routine PET-MPI interpretation. Graphic

BACKGROUND: Left ventricular ejection fraction reserve (LVEF-R), defined as stress EF minus rest EF, is a marker for high-risk coronary artery disease in patients undergoing positron emission tomography myocardial perfusion imaging, but its prognostic and diagnostic significance in large real-world populations remains incompletely defined. We aimed to analyze the association of LVEF-R with mortality and high-risk obstructive coronary artery disease in a large multicenter cohort. METHODS: We analyzed 34 976 patients from 13 sites who underwent gated rest and vasodilator stress positron emission tomography myocardial perfusion imaging from the Registry of Flow and Perfusion Imaging for Artificial Intelligence with PET. Associations between LVEF-R and all-cause mortality and cardiovascular death were assessed using multivariable Cox regression models. In a subset with invasive coronary angiography (n=6843), the relationship between LVEF-R and angiographic disease was evaluated. RESULTS: A total of 9392 (26.9%) patients had an LVEF-R5%, adjusted hazard ratios for all-cause mortality were 1.20 for LVEF-R 0% to 5% ([95% CI, 1.13–1.28]; P P P <0.001). A negative LVEF-R was also associated with high-risk coronary artery disease, including left main and 3-vessel disease. CONCLUSIONS: LVEF-R is an independent predictor of mortality, with a graded association between impaired reserve and adverse outcomes. A negative LVEF-R identifies patients with a higher likelihood of multivessel or left-main coronary artery disease, supporting its role as a clinically relevant marker of high-risk disease.

BACKGROUND: Myocardial perfusion imaging is used to guide risk stratification and revascularization decisions. We aimed to determine whether the prognostic value of ischemia on myocardial perfusion imaging and the association with early revascularization (ER) and outcomes differ across age groups. METHODS: We included 73 038 patients who underwent single photon emission computed tomography (n=45 252) or positron emission tomography (n=27 786) myocardial perfusion imaging across 20 sites from 2009 to 2024. ER was defined as revascularization within 90 days post-myocardial perfusion imaging. Propensity score-adjusted Cox models evaluated the interaction between age, ischemic burden (myocardial flow reserve for positron emission tomography), and ER for the primary outcome of all-cause death or nonfatal myocardial infarction. RESULTS: Median age was 66 years; 45.3% were 10%: 0.90 [0.64–1.26]), although precision was limited, likely reflecting, in part, the small number of patients undergoing ER (n=198). Among positron emission tomography patients, the myocardial flow reserve×ER association did not vary with age (3-way interaction P =0.689). In analyses excluding patients with ER, ischemia remained prognostic in all age groups, though its associated risk declined with advancing age. CONCLUSIONS: Ischemia remains prognostic across all ages and may help identify candidates who have improved outcomes with ER. In an exploratory analysis, this association appeared attenuated in patients aged ≥85 years, a hypothesis-generating observation. Positron emission tomography-derived myocardial flow reserve may provide complementary physiological information for treatment selection in older adults.

Background: Premature atherosclerotic cardiovascular disease (pASCVD) represents a major public health concern worldwide. This meta-analysis aimed to assess the (1) global and regional prevalence of cardiovascular risk factors (RFs) and genetic polymorphisms and (2) identify key predictors and clinically relevant cutoff values associated with pASCVD.Methods: We systematically searched electronic databases through December 2025 for studies comparing patients with pASCVD to age-matched healthy controls. Primary outcomes were global and regional prevalences of demographic, lifestyle, clinical, biochemical, and genetic risk factors. The secondary outcome was the assessment of their predictive power and determination of optimal cutoff values.Results: We included 290 studies with 8,871,668 participants (361,019 patients and 8,510,649 controls; mean age 43.2±1.3 years). Patients with pASCVD had higher prevalences of male sex, smoking, physical inactivity, high alcohol use, and other clinical risk factors and biomarkers compared with controls (all p<0.05). Genetic polymorphisms affecting endothelial function, oxidative stress, thrombosis, homocysteine metabolism, and lipid metabolism were more common in persons with pASCVD; low density lipoprotein receptor (LDLR) variants showed the strongest association with pASCVD (OR 7.97; p<0.001). The pooled prevalence of risk factors were: male sex 70%, current smoking 49%, dyslipidemia 46%, hypertension 36%, overweight 38%, obesity 29%, family history 36%, excessive alcohol use 35%, and diabetes 16%. The prevalence of current smoking was the highest in Europe (51%) and Asia (45%), hypertension was more common in the Americas, Europe, and Oceania (47, 36 and 35%, respectively); obesity was highest in the Americas and Europe (34 and 31%, respectively). Family history of CVD was similar across continents (35–42%). Smoking and overweight predominated in low-income regions, while obesity, dyslipidemia, hypertension, diabetes, and high alcohol use increased with rising income. Men had higher rates of smoking and dyslipidemia; women had higher rates of hypertension and obesity. Male sex and White and Black race were associated with increased pASCVD risk, while normal BMI was a protective factor (OR 0.50). Current smoking was the strongest lifestyle predictor (OR 3.05), followed by former smoking (OR 1.47), physical inactivity (OR 1.81), and high alcohol consumption (OR 1.85). Major clinical predictors included familial hypercholesterolemia (OR 4.05), diabetes (OR 3.65), hypertension (OR 3.10), and premature family history of pASCVD (OR 3.26). Elevated lipoprotein(a) ≥50 mg/dL (≥125 nmol/L) (OR 3.93) and LDL-C ≥160 mg/dL (≥4.1 mmol/L) (OR 3.22) showed the largest biomarker-related size effects.Interpretation: Premature ASCVD reflects early exposure to adverse cardiometabolic risk as well as genetic susceptibility. Major determinants include male sex, smoking, dyslipidemia, hypertension, obesity, and diabetes, with inflammatory biomarkers and genetic variants contributing incremental risk. Early identification of persons at risk and the initiation of intensive, life-course prevention strategies are essential to reduce the global burden of premature ASCVD.

Anthracyclines are cornerstone chemotherapeutic agents for several cancers but carry a substantial risk of cardiotoxicity. Multiple cardioprotective drugs have been investigated to prevent cardiac dysfunction in patients receiving anthracycline-based chemotherapy. This study evaluated and ranked the cardioprotective effects of these agents using network meta-analysis. A comprehensive search of PubMed, Cochrane, Scopus, and Web of Science from inception to September 22, 2024 identified randomized clinical trials and cohort studies assessing cardioprotective agents in cancer patients treated with anthracyclines. Interventions included angiotensin-converting enzyme inhibitors (ACEIs), angiotensin receptor blockers, beta-blockers, mineralocorticoid receptor antagonists, statins, sodium-glucose cotransporter 2 (SGLT2) inhibitors, and metformin. The primary outcome was change in left ventricular ejection fraction (LVEF). Secondary outcomes were left ventricular end-diastolic diameter (LVEDD), chemotherapy-related cardiac dysfunction (CTRCD), heart failure (HF), HF hospitalization, and all-cause mortality. Thirty-five studies were included, comprising 31 randomized controlled trials and 4 retrospective studies. Overall, cardioprotective therapy significantly improved LVEF, reduced CTRCD, all-cause mortality, HF incidence, and LVEDD, but had no significant effect on HF hospitalization. Subgroup and network meta-analyses showed that ACEIs plus beta-blockers, beta-blockers alone, statins, and ACEIs significantly improved LVEF versus controls, with ACEIs ranking highest. For CTRCD prevention, statins and beta-blockers significantly reduced risk, whereas ACEIs plus beta-blockers had the most favorable ranking. For mortality, the available retrospective SGLT2 inhibitor studies suggested an association with lower risk; however, because no randomized anthracycline-specific SGLT2 inhibitor trials were available and follow-up duration differed from the RCT evidence for other agents, this finding should be considered hypothesis-generating rather than definitive comparative evidence. ACEIs, beta-blockers, and statins appear effective for preserving cardiac function during anthracycline therapy. Treatment rankings, particularly for outcomes supported by sparse or observational evidence, should be interpreted cautiously, and further randomized trials are needed, particularly to evaluate SGLT2 inhibitors.

Purpose of review: Nonobstructive coronary artery disease (NOCA) is now frequently detected by coronary CT angiography (CCTA), but the term compresses biologically distinct patterns into a single anatomic label. This review examines how CT-derived markers can reorganize NOCA around plaque burden, inflammatory activity, clinical expression, and temporal change. Recent findings: Recent work distinguishes three related but distinct tasks in NOCA: identify disease, stratify risk, and define phenotypes that may inform future prevention strategies. CCTA addresses the atherosclerotic and prognostic dimensions by quantifying plaque burden, plaque composition, and high-risk features; CT-derived inflammatory and cardiometabolic markers may further identify active vascular and metabolic phenotypes. In symptomatic patients, CCTA and fractional flow reserve CT can evaluate epicardial anatomy and lesion-specific hemodynamic significance, but normal or nonobstructive findings do not exclude coronary microvascular dysfunction or vasospasm. In asymptomatic patients, coronary artery calcium and CCTA can reveal subclinical atherosclerosis and refine preventive risk assessment. Serial imaging and intervention studies suggest that adverse plaque phenotypes can stabilize or change with intensive prevention, but outcome-proven CCTA-guided treatment algorithms are still lacking. Summary: CCTA is evolving into a multidimensional phenotyping tool for NOCA. Its immediate value is refined risk stratification; whether these markers will improve outcomes remains unproven and should be tested prospectively.

Background and Aims: Epicardial adipose tissue (EAT) has emerged as an important cardiovascular biomarker that reflects both inflammatory and cardiometabolic risk. EAT volume and density vary significantly across populations, yet there is a lack of multicenter studies investigating the predictive value of population-specific EAT percentiles. Methods: In this multicenter study, we retrospectively analyzed low-dose computed tomography correction scans from 42,842 patients undergoing myocardial perfusion imaging. A derivation cohort of 15,082 patients was used to establish sex- and age-specific nomograms for EAT density and EAT volume indexed to body surface area. Percentile-based thresholds were tested for outcome prediction in a validation cohort of 27,760 patients. For clinical implementation, we developed an online EAT percentile calculator. Results: Percentile curves demonstrated increased BSA-indexed EAT volume and decreasing EAT density with age. Over a median follow-up of 3.6 years (IQR: 1.83 – 5.14), 4,956 patients experienced a nonfatal myocardial infarction or death. In multivariable Cox models, patients above the 95 ^th sex- and age-specific percentile had significantly worse outcomes for BSA-indexed EAT volume [adjusted hazard ratio 1.30, 95% CI: 1.14 – 1.49, p < 0.001] and EAT density [adjusted hazard ratio 1.7, 95% CI: 1.51 – 1.92, pth percentile (p<0.001). Conclusion: Age- and sex-specific EAT percentiles provide a clinically interpretable framework for contextualizing automated EAT measurements and identifying patients at increased cardiovascular risk. EAT density was a stronger prognostic marker and identified elevated risk even among patients with normal BMI, supporting its potential to provide information beyond conventional anthropometric assessment. Graphical