Daily Cardiology Research Analysis
Analyzed 168 papers and selected 3 impactful papers.
Summary
Analyzed 168 papers and selected 3 impactful articles.
Selected Articles
1. Fractional flow reserve-guided percutaneous coronary intervention versus medical therapy for stable coronary artery disease: long-term results of the FAME 2 trial.
In long-term follow-up (median 11.2 years), FFR-guided PCI reduced the composite of death, MI, or urgent revascularization compared with medical therapy, driven predominantly by fewer urgent revascularizations (win ratio 1.25). There was no clear mortality benefit signal, but trends favored PCI for MI and strongly for urgent revascularization.
Impact: This study provides definitive long-term evidence supporting FFR-guided PCI in stable CAD, informing durable clinical decision-making beyond 5 years. The hierarchical win-ratio approach strengthens the robustness of composite outcome comparisons over extended follow-up.
Clinical Implications: For stable CAD with FFR-positive lesions, FFR-guided PCI should be considered to reduce future urgent revascularizations and possibly MI over the long term, while shared decision-making should acknowledge limited mortality differences.
Key Findings
- Median 11.2-year follow-up: primary composite (death/MI/urgent revascularization) favored FFR-guided PCI with a win ratio of 1.25 (95% CI 1.01–1.56).
- Component outcomes: win ratios 0.88 for all-cause death, 1.50 for myocardial infarction, and 4.57 for urgent revascularization.
- Number needed to treat was 17 to achieve a win in the hierarchical composite; benefit primarily due to fewer urgent revascularizations.
Methodological Strengths
- Randomized comparison with long-term follow-up across 16 hospitals.
- Hierarchical win-ratio analysis prioritizing mortality mitigates bias from missing nonfatal outcomes in deceased patients.
Limitations
- No clear mortality reduction; benefit driven mainly by fewer urgent revascularizations.
- Evolving PCI techniques and medical therapy over a decade may introduce treatment-era heterogeneity.
Future Directions: Evaluate cost-effectiveness and quality-of-life impacts of FFR-guided PCI over longer horizons and in contemporary practice with newer stents and adjunctive pharmacotherapy.
In patients with stable coronary artery disease (CAD), the long-term benefits of revascularization over medical therapy remain unclear. In the Fractional Flow Reserve versus Angiography for Multivessel Evaluation 2 trial, patients with hemodynamically significant stenoses (fractional flow reserve (FFR) ≤ 0.80) were randomized to receive FFR-guided percutaneous coronary intervention (PCI) plus medical therapy (n = 447) or medical therapy alone (n = 441). At 5 years, FFR-guided PCI reduced the risk of the primary composite outcome of time to death, myocardial infarction or urgent revascularization, largely because of fewer urgent revascularizations. We now report the long-term clinical outcomes from this trial. Sixteen hospitals, contributing 748 randomized patients (161 women, 21.5%), participated in the long-term follow-up. The primary composite outcome was analyzed hierarchically using the unstratified win ratio, which addressed differential missingness of data on nonfatal outcomes in deceased patients by prioritizing comparisons on time to death. At a median follow-up of 11.2 years, the primary endpoint occurred in 150 of 447 patients (33.6%) in the PCI group versus 182 of 441 (41.3%) in the medical therapy group. PCI was superior in 29.2% of comparisons, medical therapy in 23.3%, and the two groups were tied in 47.5%, resulting in a win ratio of 1.25 in favor of PCI (95% confidence interval (CI) 1.01-1.56, P = 0.043). The corresponding win difference was 5.9% (95% CI 0.2-11.6), and the number needed to treat was 17 (95% CI 9-500). Win ratios were 0.88 for all-cause death (95% CI 0.66-1.17), 1.50 for myocardial infarction (95% CI 0.98-2.31) and 4.57 for urgent revascularization (95% CI 2.53-8.24). During long-term follow-up, FFR-guided PCI in patients with stable CAD and hemodynamically significant stenoses reduced the composite of death, myocardial infarction or urgent revascularization, primarily because of fewer urgent revascularizations. These long-term findings reaffirm the efficacy of FFR-guided PCI over medical therapy in patients with stable CAD. ClinicalTrials.gov registration: NCT06159231 .
2. An unbiased molecular characterisation of peripartum cardiomyopathy hearts identifies mast cell chymase as a new diagnostic candidate.
Using multi-omics profiling of human PPCM hearts, the authors identified mast cell activation with robust upregulation of chymase and carboxypeptidase A3 as PPCM-specific features. Serum chymase levels strongly predicted cardiomyopathy among peripartum women, positioning chymase as a promising diagnostic biomarker.
Impact: This study bridges mechanistic tissue insights with translational serum biomarker data, addressing a major diagnostic gap in PPCM. It offers a plausible path toward earlier and more specific diagnosis in a high-risk population.
Clinical Implications: Serum chymase may facilitate earlier, noninvasive diagnosis of PPCM and help distinguish it from non-peripartum dilated cardiomyopathy, potentially guiding monitoring and targeted therapies.
Key Findings
- PPCM hearts exhibited consistent upregulation of mast cell proteins chymase and carboxypeptidase A3 across deep proteomics, single-nucleus, and spatial transcriptomics.
- Serum proteomics in a larger peripartum cohort showed chymase strongly predicted cardiomyopathy in peripartum women.
- Canonical end-stage heart failure markers were regulated in both PPCM and NPCM, but mast cell–related changes were PPCM-specific.
Methodological Strengths
- Orthogonal, multi-omics characterization (deep proteomics, single-nucleus and spatial transcriptomics) in human tissue with appropriate controls and NPCM comparators.
- Translational validation via serum proteomics in an expanded peripartum cohort.
Limitations
- Tissue analyses are derived from end-stage disease samples; exact sample sizes and selection criteria are not specified in the abstract.
- Observational, cross-sectional design limits causal inference and therapeutic validation.
Future Directions: Prospective diagnostic studies to establish serum chymase thresholds and performance, mechanistic dissection of mast cell pathways in PPCM, and exploration of chymase or mast cell–targeted therapies.
BACKGROUND: Peripartum cardiomyopathy (PPCM) is a rare form of acute heart failure that develops in women towards the end of pregnancy or early postpartum. No effective, specific treatment for PPCM is available and heart transplantation or mechanical circulatory support may be required in severe cases where drug treatment for heart failure is insufficient. The mechanisms through which the disease progresses are not well understood, and despite similar clinical characteristics to dilated cardiomyopathy of other aetiologies (non-peripartum cardiomyopathy; NPCM) it is not known how the molecular remodelling differs between these groups. We aimed to provide insight into the human PPCM heart using unbiased methodologies, and to use changes occurring within the heart tissue to facilitate biomarker discovery. METHODS: We obtained heart tissue from female patients with end stage disease receiving either heart transplantation or left ventricular assist device implantation, or from organ donors without heart disease as a control group. We performed deep proteomics, single nucleus transcriptomics and spatial transcriptomics, providing a comprehensive map of the molecular phenotype in advanced PPCM compared to both control and NPCM hearts. CENTRAL FINDINGS: Consistent with similarities in the clinical phenotypes of PPCM and NPCM, we observed regulation of canonical markers of end-stage heart failure in both PPCM and NPCM hearts in comparison to controls. Among the changes specific to PPCM and that were consistently observed across multiple data types and cohorts was an upregulation of chymase and carboxypeptidase A3, consistent with mast cell proliferation/activation. Analysis of the proteome of peripheral blood serum from a larger cohort of patients with PPCM and controls showed that chymase was strongly predictive of cardiomyopathy in peripartum women. CONCLUSIONS: PPCM heart tissue is characterised by increased mast cell proteins chymase and carboxypeptidase A3. Chymase may have clinical utility as a biomarker for the diagnosis of cardiomyopathy in peripartum women.
3. Simultaneous Bright- and Black-Blood 3D Whole-Heart MRI for Integrated Coronary Plaque Detection and Luminal Stenosis Assessment: A Prospective Comparison with CT Coronary Angiography.
In a prospective head-to-head comparison with CCTA, the BOOST CMR sequence detected 88% of plaques and achieved 81% agreement in stenosis grading, while quantifying plaque signal (PMR) across plaque types. It enables simultaneous lumen and plaque assessment in a single, non-contrast, free-breathing acquisition.
Impact: This sequence integrates anatomical lumen imaging with vessel wall/plaque characterization without radiation or contrast, addressing a key limitation of current first-line testing. It could broaden access to comprehensive coronary assessment in patients unsuitable for CCTA.
Clinical Implications: BOOST CMR may serve as a radiation- and contrast-free alternative for anatomical and plaque imaging in stable chest pain, particularly in patients with renal dysfunction or contrast allergy, pending larger validation and outcome studies.
Key Findings
- BOOST detected 63/72 (88%) CCTA-identified plaques and showed 81% agreement with CCTA in stenosis grading across severity categories.
- Plaque-to-myocardium ratio (PMR) was significantly higher than healthy vessel-to-myocardium ratio (0.64 ± 0.16 vs 0.36 ± 0.11; p<0.001) across calcified, partially calcified, and non-calcified plaques.
- Hypertension and family history of premature cardiovascular disease were associated with higher PMR values.
Methodological Strengths
- Prospective, within-patient comparison to CCTA with predefined quantitative metrics (PMR/HVMR).
- Single non-contrast, free-breathing acquisition generating co-registered bright- and black-blood images.
Limitations
- Single-center sample of 60 patients; reduced agreement in moderate-to-severe stenosis categories.
- No invasive angiographic gold standard or clinical outcomes were assessed.
Future Directions: Multicenter validation with larger cohorts, inclusion of invasive reference standards and outcomes, and optimization for challenging lesion subtypes.
BACKGROUND: Coronary computed tomographic angiography (CCTA) is a first-line test for anatomical evaluation of the coronary arteries in stable chest pain. Despite technical advances, CCTA requires breath hold and exposes patients to ionising radiation and contrast agents. Coronary cardiovascular magnetic resonance angiography (CCMRA) has been limited by long and unpredictable scan times, lower spatial resolution, and restricted plaque characterisation. We developed a novel CMR sequence, BOOST, which produces a co-registered bright-blood image for lumen visualisation and a T1-weighted black-blood image for vessel wall and plaque assessment from a single scan with predictable scan times. OBJECTIVES: To compare the BOOST-CCMRA sequence with CCTA for plaque characterisation and stenosis evaluation in patients with stable chest pain. METHODS: 60 consecutive patients (mean age 56 years, 60% male) with stable chest pain were prospectively enrolled. All underwent CCTA followed by BOOST-CCMRA on a 1.5T MRI scanner. Coronary plaques identified on CCTA and were analysed on the black-blood BOOST image using the signal from plaque to derive the plaque-to-myocardium ratio (PMR); a healthy vessel-to-myocardium ratio (HVMR) was derived as reference. Plaque morphology was assessed by CCTA appearance. Luminal stenosis was assessed on BOOST bright-blood images and compared with CCTA. RESULTS: Of 60 patients, 35 had plaque on CCTA, with 72 plaques identified. Nine were not detected on BOOST, giving an 88% detection success. BOOST showed agreement with CCTA in stenosis grading for 51 of 63 lesions (81%): 23/26 (88%) minimal, 20/24 (83%) mild, 4/7 (57%) moderate, 3/5 (60%) severe, and 1/1 (100%) occlusion. PMR was significantly higher than HVMR (0.64 ± 0.16 vs 0.36 ± 0.11; p < 0.001) across all plaque subtypes (calcified 0.53 ± 0.11, partially calcified 0.70 ± 0.15, non-calcified 0.69 ± 0.16, all p < 0.001 vs HVMR). Hypertension and family history of premature cardiovascular disease were associated with higher PMR values. CONCLUSIONS: The BOOST sequence allows simultaneous evaluation of coronary lumen and plaque characteristics in a single non-contrast CCMRA acquisition, with reliable plaque identification and good agreement with CCTA for stenosis severity assessment. This approach may offer free-breathing alternative, without radiation or contrast, for integrated anatomical and plaque imaging in patients with stable chest pain.