Daily Cardiology Research Analysis
Analyzed 130 papers and selected 3 impactful papers.
Summary
Three impactful cardiology studies stood out today: a large NEJM randomized trial found no reduction in coronary-artery lesions with adjunctive prednisolone in unselected Kawasaki disease; a JACC RCT showed a sirolimus drug-eluting balloon is noninferior to usual care but inferior to repeat DES for single-layer in-stent restenosis; and a JAMA Cardiology imaging study demonstrated that [68Ga]FAPI-46 PET quantifies myocardial fibroblast activation and predicts reverse remodeling patterns in heart failure.
Research Themes
- Anti-inflammatory therapy in Kawasaki disease
- Drug-eluting balloon vs DES for coronary in-stent restenosis
- Molecular imaging of cardiac fibroblast activation in heart failure
Selected Articles
1. Randomized Trial of Adjunctive Prednisolone for Kawasaki Disease.
In a multicenter open-label RCT of 3,208 children with Kawasaki disease, adjunctive prednisolone did not reduce 1-month coronary-artery lesions versus standard therapy alone. Although fever resolved faster and CRP fell more with prednisolone and fewer needed rescue therapy, coronary outcomes and adverse events were similar through 3 months.
Impact: This large, well-conducted RCT provides definitive evidence against routine steroid add-on in unselected Kawasaki disease, challenging practices extrapolated from high-risk subgroups.
Clinical Implications: Do not routinely add prednisolone to initial IVIG-based therapy in unselected Kawasaki disease. Consider steroids only for validated high-risk phenotypes or refractory cases within evidence-based protocols.
Key Findings
- Primary endpoint: 1-month coronary-artery lesions 16.0% (prednisolone) vs 13.8% (standard), adjusted risk difference 1.1% (95% CI -1.0 to 3.4; P=0.31).
- Rescue therapy use was lower with prednisolone (4.6% vs 10.1%); median fever duration was shorter (8.4 vs 13.2 hours).
- CRP reduction at 72 hours was greater with prednisolone (67.5 vs 59.8 mg/L), but coronary z-score changes and 3-month coronary outcomes were similar.
- Medium-to-giant aneurysms at 3 months: 1.9% (prednisolone) vs 1.1% (standard); adverse events were similar between groups.
Methodological Strengths
- Large multicenter randomized controlled design with prespecified outcomes and trial registration.
- Robust sample size (N=3,208) enabling precise coronary outcomes assessment.
Limitations
- Open-label design may influence secondary symptom-based outcomes.
- Primary endpoint assessed at 1 month; generalizability beyond Chinese population and to specific high-risk phenotypes warrants caution.
Future Directions: Refine risk stratification to target glucocorticoids to validated high-risk KD subgroups; test alternative anti-inflammatory strategies with coronary endpoints and longer follow-up.
BACKGROUND: The effect of adjunctive glucocorticoids in the primary treatment of Kawasaki disease in unselected patients remains unknown. METHODS: In this multicenter, open-label, randomized, controlled trial in China, we assigned participants with newly diagnosed Kawasaki disease in a 1:1 ratio to receive prednisolone plus standard treatment or standard treatment alone. The primary outcome was the occurrence of coronary-artery lesions at 1 month after illness onset. Prespecified key secondary outcomes, for which analyses were not controlled for multiplicity, included receipt of rescue therapy, duration of fever, change in the C-reactive protein (CRP) level, and changes in coronary-artery z scores. RESULTS: A total of 3208 participants underwent randomization, with coronary-artery lesions detected at baseline in 870 of 3184 participants (27.3%). At 1 month, coronary-artery lesions were detected in 16.0% of the participants receiving prednisolone plus standard treatment and in 13.8% of those receiving standard treatment alone (adjusted risk difference, 1.1 percentage points; 95% confidence interval, -1.0 to 3.4; P = 0.31). Rescue therapy was used in 4.6% of the participants receiving prednisolone plus standard therapy and in 10.1% of those receiving standard treatment alone; the median duration of fever was 8.4 hours and 13.2 hours, respectively, and the reductions in the C-reactive protein level at 72 hours were 67.5 mg per liter and 59.8 mg per liter. Decreases in coronary-artery z scores were similar in the two groups. At 3 months, the incidence of coronary-artery lesions was 12.6% with prednisolone plus standard therapy and 10.5% with standard treatment alone; the percentage of participants with progression of coronary-artery lesions was 28.6% and 28.9%, respectively, and the incidence of medium-to-giant coronary-artery aneurysms was 1.9% and 1.1%. The overall incidence of adverse events did not differ significantly between the two groups. CONCLUSIONS: The addition of prednisolone to standard primary treatment for Kawasaki disease did not reduce the incidence of coronary-artery lesions at 1 month after illness onset. (Funded by the Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences and the National Natural Science Foundation of China; ClinicalTrials.gov number, NCT04078568.).
2. Sirolimus-Eluting Balloon vs Repeat Drug-Eluting Stent or Balloon Angioplasty for Coronary In-Stent Restenosis.
In the SELUTION4ISR RCT (n=418 randomized; per-protocol n=390), a sirolimus drug-eluting balloon was noninferior to a usual-care strategy (80% repeat DES) for 12-month target lesion failure. However, in single-layer ISR, the DEB was not noninferior to repeat DES, while outperforming plain balloon angioplasty; outcomes varied by operator-selected comparator.
Impact: This RCT refines treatment selection for ISR by positioning sirolimus DEB as a viable alternative when additional metal layers are undesirable, while confirming repeat DES superiority in single-layer ISR.
Clinical Implications: Consider sirolimus DEB as an option for ISR when avoiding further stent layers (e.g., small vessels, high metal burden), but favor repeat DES for single-layer ISR where long-term patency is critical. Lesion morphology and prior layers should guide therapy.
Key Findings
- Per-protocol 12-month TLF: 16.2% (DEB) vs 14.5% (control; mostly DES), meeting noninferiority to usual care.
- In single-layer ISR, DEB had higher TLF than DES (14.2% vs 6.5%), failing noninferiority to DES.
- DEB outperformed plain balloon angioplasty (lower TLF), with significant interaction by operator-selected comparator.
- No device-related complications reported; overall 30-day MACE 3.9%.
Methodological Strengths
- Randomized, controlled, multicenter design with prespecified Bayesian noninferiority framework.
- Clinically relevant composite endpoint (TLF) and stratified secondary analysis for single-layer ISR.
Limitations
- Primary analysis per-protocol rather than intention-to-treat; operator preselection of comparator introduces potential selection bias.
- Follow-up limited to 12 months; heterogeneity of ISR substrates not fully characterized.
Future Directions: Head-to-head DES vs DEB trials with ITT analyses across ISR phenotypes, longer follow-up, and intravascular imaging-defined substrates to optimize patient selection.
BACKGROUND: Drug-eluting stents (DESs) are recommended treatment for coronary in-stent restenosis (ISR) but are not used in >20% of cases. OBJECTIVES: The aim of the SELUTION4ISR (SELUTION SLR 014 In-stent Restenosis) trial was to assess the safety and effectiveness of a novel sirolimus drug-eluting balloon (DEB). METHODS: After successful lesion predilation, patients with ISR were randomly assigned to the SELUTION Sustained Limus Release (MedAlliance) DEB or a control strategy of usual care, including any approved DES or balloon angioplasty (BA) on the basis of operator selection prerandomization. Randomization to selected BA control treatment was limited to 20% of patients. The primary outcome was target lesion failure (TLF) (cardiac death, target vessel myocardial infarction, or clinically driven target lesion revascularization) assessed at 1 year in the per protocol group (all treated eligible patients with complete primary endpoint follow-up). Noninferiority was established if the upper limit of the 2-sided 95% credible interval was smaller than 10%. A sequential secondary hypothesis test was performed comparing DEB with DES in patients with single-layer ISR. RESULTS: From July 2020 to July 2024, 418 patients were randomly assigned to the DEB group (n = 210) or the control group (n = 208), with 390 patients per protocol (DEB, 197; control, 193 [154 DES; 39 BA]). TLF occurred in 32 (16.2%) of 197 patients in the DEB group and in 28 (14.5%) of 193 patients in the control group (difference: 1.7%; 95% credible interval: -5.5% to 8.9%; posterior probability of noninferiority: 98.80%). In the secondary hypothesis test, TLF occurred in 22 (14.2%) of 155 patients in the DEB group and in 9 (6.5%) of 138 patients in the DES control group (difference: 7.7%; 95% credible interval: 0.6%-14.6%, posterior probability for noninferiority: 76.07%). TLF according to operator selected control was higher for DEB compared with DES (15.3% vs 7.1%; difference: 8.1%; 95% credible interval: 1.4%-15.0%) and lower for DEB compared with BA (23.6% vs 43.6%; difference: 23.7%; 95% credible interval: -41.4% to -1.5%; P CONCLUSIONS: The sirolimus DEB was noninferior to a usual care control strategy including 80% repeat DES but not noninferior to DES for single-layer ISR for TLF at 12 months. There was significant interaction on the basis of operator selection of DES vs BA. (SELUTION SLR 014 In-stent Restenosis [SELUTION4ISR]; NCT04280029).
3. Myocardial Fibroblast Activation in Ischemic and Nonischemic Cardiomyopathy.
[68Ga]FAPI-46 PET/MRI revealed elevated myocardial fibroblast activation in HFrEF versus healthy controls, with focal high uptake in ischemic scars and diffuse lower-intensity uptake in nonischemic disease. Higher baseline uptake predicted less EF improvement over >6 months of optimized therapy.
Impact: Introduces a noninvasive biomarker of active myocardial fibrogenesis that differentiates etiologies and forecasts reverse remodeling, enabling precision phenotyping and antifibrotic trial enrichment.
Clinical Implications: [68Ga]FAPI-46 PET may complement CMR in heart failure phenotyping, identifying patients with active fibroblast signaling who are less likely to improve EF and who may benefit from targeted antifibrotic strategies.
Key Findings
- HFrEF patients had higher [68Ga]FAPI-46 SUVmax than healthy volunteers (2.7 vs 1.5; P<.001); healthy volunteers showed no activation.
- Ischemic cardiomyopathy showed highest uptake localized to infarcted regions (SUVmax ~3.2), whereas nonischemic cardiomyopathy showed diffuse lower-intensity uptake (SUVmax ~2.3) with basal septal predominance.
- Higher baseline FAPI uptake correlated with less EF improvement over >6 months (r=-0.52; P=.02).
- Ischemic cardiomyopathy had higher uptake than prior MI without HF despite similar infarct size (SUVmax 3.2 vs 2.5; P=.03).
Methodological Strengths
- Prospective case-control design including healthy volunteers, prior MI without HF, and HFrEF.
- Hybrid PET/MRI with quantitative SUV and repeat imaging to link baseline activation to remodeling.
Limitations
- Modest sample size and case-control design limit causal inference and generalizability.
- Access to [68Ga]FAPI-46 and standardization of acquisition/thresholds remain logistical hurdles.
Future Directions: Multicenter prognostic studies and interventional trials targeting fibroblast activation guided by FAPI PET to test antifibrotic therapies and refine thresholds for clinical use.
IMPORTANCE: Adverse myocardial remodeling and fibrosis contribute to heart failure progression and are thought to be driven by activated fibroblasts. Noninvasive assessment of myocardial fibroblast activation may improve phenotyping and risk stratification in heart failure. OBJECTIVE: To evaluate myocardial fibroblast activation in patients with heart failure with reduced ejection fraction using gallium 68-labeled fibroblast activation protein inhibitor 46 ([68Ga]FAPI-46) positron emission tomography (PET) and magnetic resonance imaging (MRI). DESIGN, SETTING, AND PARTICIPANTS: This was a prospective case-control study including patients with heart failure with reduced ejection fraction, patients with prior myocardial infarction without heart failure, and healthy volunteers. A subset of patients with heart failure underwent repeat imaging after more than 6 months. Data analysis was conducted from January 2024 to January 2025. EXPOSURE: All participants underwent [68Ga]FAPI-46 PET/MRI. MAIN OUTCOMES AND MEASURES: Myocardial fibroblast activation quantified using maximum standardized uptake values (SUVmax) of [68Ga]FAPI-46. RESULTS: A total of 81 participants were included (mean [SD] age, 66.2 [9.7] years; 22 [27%] female): 42 with heart failure (21 with heart failure due to ischemic cardiomyopathy from a previous myocardial infarction and 21 with a nonischemic etiology; mean [SD] left ventricular ejection fraction, 41% [9%]), 20 with a prior myocardial infarction but preserved left ventricular systolic function, and 19 healthy volunteers. No myocardial fibroblast activation was observed in healthy volunteers. All patients with heart failure demonstrated increased myocardial [68Ga]FAPI-46 uptake compared with healthy volunteers (mean [SD] SUVmax, 2.7 [1.5] vs 1.5 [0.3]; P < .001). Uptake was highest in patients with ischemic cardiomyopathy, localizing to regions of established myocardial infarction (mean [SD] SUVmax, 3.2 [1.1]). Patients with nonischemic cardiomyopathy exhibited a different pattern of diffuse, lower-intensity uptake (mean [SD] SUVmax, 2.3 [0.5]), with the highest signal in the basal septum irrespective of late gadolinium enhancement. Patients with ischemic cardiomyopathy had higher uptake than patients with prior myocardial infarction without heart failure (n = 20) despite no major difference in infarct size (mean [SD] SUVmax, 3.2 [1.1] vs 2.5 [0.3]; P = .03). Among patients with heart failure who underwent repeat imaging, higher baseline [68Ga]FAPI-46 uptake was associated with less improvement in ejection fraction with optimal medical therapy over time (r = -0.52; P = .02). CONCLUSIONS AND RELEVANCE: In this case-control study, patients with heart failure demonstrated persistent myocardial fibroblast activation with distinct spatial patterns according to cardiomyopathy etiology. Noninvasive imaging of fibroblast activation may provide mechanistic insights, aid risk stratification, and support the development of targeted antifibrotic therapies in heart failure.