Daily Cardiology Research Analysis
Three high-impact studies advance cardiology across diagnosis, imaging, and population risk. An AI-enabled, demographically adjusted LVH threshold improves hypertrophic cardiomyopathy diagnosis and reduces sex/body-size bias. A large population-based cohort shows slow ascending aorta growth and low absolute event rates, informing surveillance intervals, while FAPI PET/MR maps fibroblast activation after MI, revealing an early peak and prolonged activity linked to adverse remodeling.
Summary
Three high-impact studies advance cardiology across diagnosis, imaging, and population risk. An AI-enabled, demographically adjusted LVH threshold improves hypertrophic cardiomyopathy diagnosis and reduces sex/body-size bias. A large population-based cohort shows slow ascending aorta growth and low absolute event rates, informing surveillance intervals, while FAPI PET/MR maps fibroblast activation after MI, revealing an early peak and prolonged activity linked to adverse remodeling.
Research Themes
- Personalized diagnostic thresholds in cardiomyopathy
- Molecular imaging of post-MI remodeling (FAPI PET/MR)
- Population-based risk and surveillance of ascending aortic disease
Selected Articles
1. Demographic-Based Personalized Left Ventricular Hypertrophy Thresholds for Hypertrophic Cardiomyopathy Diagnosis.
Using AI-derived CMR measurements across >50,000 individuals, the authors show that age-, sex-, and BSA-adjusted LVH thresholds (10–17 mm) substantially reduce misclassification and sex/body-size bias compared with the fixed 15-mm rule. Personalized z-scores improved HCM ascertainment, especially in women who often have lower absolute MWT but higher standardized burden.
Impact: This work challenges the long-standing 15-mm LVH criterion and offers a validated, equitable diagnostic framework that could reshape HCM detection and guideline thresholds.
Clinical Implications: Adopting demographically adjusted LVH thresholds and z-scores can reduce underdiagnosis in women and smaller-bodied individuals, refine referral for genetic testing, and better target surveillance in suspected HCM.
Key Findings
- Demographically adjusted LVH thresholds (10–17 mm) halved LVH ascertainment in the population cohort (4.3% to 2.2%) and reduced male skew from 89% to 56%.
- In the HCM cohort, a substantial fraction diagnosed with MWT <15 mm dropped from 27% to 7% (women) and 18% to 15% (men) using adjusted thresholds.
- Women showed lower absolute MWT but higher MWT z-scores, highlighting the need for standardized, personalized diagnostic metrics.
Methodological Strengths
- Very large, multi-cohort CMR dataset with AI-assisted standardized measurements.
- Use of z-scores and demographic adjustment to rigorously address bias across sex and body size.
Limitations
- Observational design without interventional validation of clinical outcomes using adjusted thresholds.
- Generalizability to non-CMR modalities (e.g., echocardiography) requires further study.
Future Directions: Prospective clinical trials should test whether adjusted thresholds improve outcomes, refine echocardiographic translation, and support guideline updates for HCM diagnosis.
BACKGROUND: Hypertrophic cardiomyopathy (HCM) is a leading cause of sudden cardiac death. Current diagnosis emphasizes the detection of left ventricular hypertrophy (LVH) using a fixed threshold of ≥15-mm maximum wall thickness (MWT). This study proposes a method that considers individual demographics to adjust LVH thresholds as an alternative to a 1-size-fits-all approach. METHODS: Left ventricular MWT was measured in 3 cohorts: a Reference Cohort of healthy adults (n = 5,067, no comorbidities), a Population Cohort (n = 43,239, with comorbidities), and an HCM Cohort from 6 international centers (n = 2,424). Measurement used cardiovascular magnetic resonance (CMR) and a validated artificial intelligence algorithm. The Reference Cohort was used to developed demographically adjusted LVH thresholds, and individualized z-scores based on age, sex, and body surface area (BSA), which were used to explore the other cohorts. RESULTS: The traditional ≥15-mm threshold classified 4.3% (n = 1,854) of the Population Cohort as hypertrophic, with a significant sex skew (89% male). Demographic-adjusted LVH thresholds (range: 10-17 mm) reduced ascertainment to 2.2% (n = 945), reducing the sex skew (56% male). Similar reductions in bias with height, weight, and age also occurred. The HCM cohort was found to have a 2:1 male-to-female ratio. A significant proportion of patients received diagnoses of HCM despite having MWT below the traditional LVH threshold (<15 mm): 27% of female individuals and 18% of male individuals. Using demographic-adjusted LVH thresholds reduced these proportions to 7% of female individuals and 15% of male individuals (P < 0.0001). Female patients had lower absolute MWT (18 mm vs 19 mm; P < 0.001) but higher MWT z-scores (5.1 vs 4.5; P = 0.05). CONCLUSIONS: Age, sex, and body size influence the normal heart MWT. Using a fixed LVH threshold ≥15 mm biases LVH ascertainment in both population and HCM cohorts. A demographic-adjusted approach for LVH improves ascertainment and diagnostic accuracy.
2. The Nonsyndromic Ascending Thoracic Aorta in a Population-Based Setting: A 5-Year Prospective Cohort Study.
In a population-based prospective cohort, nonsyndromic ascending aorta growth was very slow (≈0.07–0.13 mm/year), and AAEs were rare (0.2% over ≈5 years). Diameter increment and family history independently predicted AAE, supporting individualized surveillance intervals beyond diameter alone.
Impact: These data provide real-world, prospective benchmarks for growth and event rates, challenging frequent surveillance for many and informing cost-effective, risk-tailored follow-up.
Clinical Implications: For many nonsyndromic adults, longer imaging intervals may be safe; risk models should incorporate diameter trajectory and family history rather than diameter alone.
Key Findings
- Mean ascending aorta growth was 0.07 mm/year (men) and 0.13 mm/year (women); growth did not accelerate with larger baseline diameters.
- AAEs were uncommon (0.2% over ≈5 years across 14,962 participants), with most events occurring at diameters <50 mm.
- Each 1-mm increase in diameter (HR 1.24) and family history (HR 5.43) independently increased AAE risk, supporting individualized surveillance.
Methodological Strengths
- Population-based, multicenter, prospective design with ECG-gated non-contrast CT and registry-linked outcomes.
- Large cohort for event estimation and separate imaging subset with serial scans for growth-rate calculation.
Limitations
- Predominantly male cohort limits generalizability to women; larger female cohorts are needed.
- Imaging limited to noncontrast CT; biomechanical factors or genetic modifiers were not assessed.
Future Directions: Develop and validate risk tools combining diameter, growth rate, family history, and clinical factors; test surveillance intervals prospectively, especially in women.
BACKGROUND: Prospective data on the clinical course of the ascending thoracic aorta are lacking. OBJECTIVES: This study sought to estimate growth rates of the ascending aorta and to evaluate occurrences of adverse aortic events (AAEs)-that is, thoracic aortic ruptures, type A aortic dissections, and thoracic aortic-related deaths. METHODS: In this prospective cohort study from the population-based, multicenter, randomized DANCAVAS (Danish Cardiovascular Screening trials) I and II, participants underwent cardiovascular risk assessments including electrocardiogram-gated, noncontrast computed tomography (CT) scans. The clinical database was supplemented with outcome data from Danish health care registries. Exclusion criteria were connective tissue disorders, bicuspid aortic valves, and survivors of a prior AAE. To estimate growth rates, participants with consecutive CT scans were followed from inclusion to last scan. To evaluate AAEs, the entire cohort was followed from inclusion to AAE; elective ascending aortic surgery; death; or December 31, 2021. RESULTS: In 2,026 individuals (77.3% men; mean age: 69.2 ± 3.1 years; median follow-up: 4.5 years [Q1-Q3: 3.4-4.7 years]), 4,897 CT scans were obtained, encompassing 1,374 individuals with baseline ascending aortas of <40.0 mm (68.3% men), 388 with baseline ascending aortas between 40.0 and 44.9 mm (94.5% men), 188 with baseline ascending aortas between 45.0 and 49.9 mm (98.4% men), and 76 men with baseline ascending aortas of ≥50 mm. The mean ascending aortic growth rates in men and women were 0.07 ± 0.5 mm/year and 0.13 ± 0.3 mm/year (P = 0.012), respectively. Growth rates did not increase with larger diameters, and no differences were observed between small (<39.9 mm; 0.11 ± 0.5 mm/year) and large (≥50 mm; 0.07 ± 0.6 mm/year) (P = 0.60) aortas. In men with dilated aortas between 45.0 and 49.9 mm, 3.2% progressed to ≥50.0 mm over 4.6 years (Q1-Q3: 4.0-5.6 years). Among all 14,962 nonsyndromic participants (95.0% men; mean age: 67.7 ± 3.7 years; median follow-up: 5.0 years [Q1-Q3: 4.1-5.8 years]), 23 (0.2%) encountered AAEs (31/100,000 person-years), and 26 (0.2%) underwent elective ascending aortic surgery. In size groups of <40.0, 40.0 to 44.9, 45.0 to 49.9, and ≥50.0 mm, proportions of AAEs were 10 of 11,382 (0.1%), 5 of 2,997 (0.2%), 7 of 493 (1.4%), and <3 of 90, respectively. Adjusted HRs for AAE were 1.24 (95% CI: 1.16-1.33; P < 0.001) for each 1-mm increase in diameter and 5.43 (95% CI: 1.99-14.82; P = 0.001) for a family history of aortic aneurysms. CONCLUSIONS: In men aged 60 to 74 years, growth of the ascending aorta was slow, questioning the currently recommended (bi)annual surveillance scan intervals. Additionally, 95% of AAE case patients presented with diameters of <50.0 mm upon the event, highlighting the need for individualized risk stratifications in addition to diameter. Larger prospective studies in aneurysmal women are warranted.
3. Myocardial Fibroblast Activation After Acute Myocardial Infarction: A Positron Emission Tomography and Magnetic Resonance Study.
Using [68Ga]-FAPI PET/MR in 40 MI patients, fibroblast activation peaked within one week, extended beyond infarct territories, and persisted for years with gradual decline. Activity levels correlated with subsequent LV remodeling, highlighting a therapeutic window and a candidate biomarker for anti-fibrotic strategies.
Impact: First-in-human serial mapping of fibroblast activation dynamics after MI provides a mechanistic imaging biomarker linked to remodeling, enabling precision timing for anti-fibrotic therapies.
Clinical Implications: FAPI PET/MR may guide risk stratification and the initiation/monitoring of anti-fibrotic interventions in the subacute phase of MI to mitigate adverse remodeling.
Key Findings
- Fibroblast activation peaked within 1 week post-MI and extended beyond the infarct region.
- Activation declined slowly but persisted for years, indicating prolonged remodeling biology.
- Higher FAPI signal was associated with subsequent LV remodeling, suggesting prognostic utility and a therapeutic window.
Methodological Strengths
- Hybrid PET/MR enables simultaneous molecular (FAPI) and structural/functional assessment.
- Serial time-course characterization provides dynamic insights rather than static snapshots.
Limitations
- Single-center, modest sample size (n=40) limits generalizability and outcome power.
- Radiotracer availability and standardization may constrain widespread clinical adoption.
Future Directions: Multicenter studies to validate prognostic thresholds, test anti-fibrotic therapies timed to peak activation, and evaluate cost-effectiveness and clinical utility.
BACKGROUND: Myocardial fibrosis is a key healing response after myocardial infarction driven by activated fibroblasts. Gallium-68-labeled fibroblast activation protein inhibitor ([ OBJECTIVES: The aim of this study was to investigate the intensity, distribution, and time-course of fibroblast activation after acute myocardial infarction. METHODS: A total of 40 patients with acute myocardial infarction underwent hybrid [ RESULTS: Myocardial [ CONCLUSIONS: Myocardial fibroblast activation peaks within a week of acute myocardial infarction and extends beyond the infarct region. It declines slowly with time, persists for years, and is associated with subsequent left ventricular remodeling. (PROFILE-MI-The FAPI Fibrosis Study; NCT05356923).