Daily Cardiology Research Analysis
Three impactful cardiology studies span intervention, device therapy, and precision systems biology. A double-blind randomized trial found periprocedural colchicine reduced new arrhythmias and leaflet thrombosis after TAVR but increased stroke risk, urging caution. An open-label RCT of an implanted microcurrent device improved LVEF, symptoms, and function in non-ischemic HFrEF, while proteomics-driven computational models predicted LVAD response from myocardial substrate preference, suggesting a
Summary
Three impactful cardiology studies span intervention, device therapy, and precision systems biology. A double-blind randomized trial found periprocedural colchicine reduced new arrhythmias and leaflet thrombosis after TAVR but increased stroke risk, urging caution. An open-label RCT of an implanted microcurrent device improved LVEF, symptoms, and function in non-ischemic HFrEF, while proteomics-driven computational models predicted LVAD response from myocardial substrate preference, suggesting avenues for metabolic personalization.
Research Themes
- Inflammation modulation and safety trade-offs in structural heart interventions
- Bioelectronic therapy to augment heart failure remodeling
- Computational precision phenotyping of myocardial metabolism to guide therapy
Selected Articles
1. Colchicine in patients with aortic stenosis undergoing transcatheter aortic valve replacement: a double-blind randomized trial.
Periprocedural colchicine reduced 30-day composite arrhythmic events and subclinical leaflet thrombosis after TAVR but was associated with an increased stroke signal leading to early trial termination. The double-blind design supports efficacy, yet safety concerns preclude routine use pending confirmatory studies.
Impact: This is the first randomized, double-blind evidence testing anti-inflammatory therapy at TAVR showing both benefit and harm, immediately informing procedural pharmacotherapy and safety monitoring.
Clinical Implications: Avoid routine periprocedural colchicine after TAVR outside trials; if considered, ensure vigilant stroke risk assessment and monitoring. Future protocols should balance arrhythmia prevention with cerebrovascular safety.
Key Findings
- Primary endpoint (new-onset AF or AV block requiring PPM at 30 days) was lower with colchicine: 10% vs 25% (risk difference −15.0%; p=0.031).
- Subclinical leaflet thrombosis was reduced with colchicine on imaging: 27% vs 54% (risk difference −27.1%; p=0.007).
- Stroke occurred more frequently with colchicine (8.3% vs 0%), triggering early termination (p=0.022).
Methodological Strengths
- Double-blind, placebo-controlled randomized design with intention-to-treat analysis
- Pre-specified imaging endpoint for leaflet thrombosis and interim safety monitoring
Limitations
- Single-centre, modest sample size; early termination limits power and generalizability
- Not powered for stroke; detailed dosing/timing strategies may influence risk
Future Directions: Conduct multicentre, adequately powered RCTs to confirm efficacy and delineate cerebrovascular risk; evaluate dose/timing, risk stratification, and mechanisms (e.g., platelet-leukocyte interactions, valve manipulation) underlying stroke signal.
An inflammatory process may increase the risk of arrhythmias after transcatheter aortic valve replacement (TAVR). In this single-centre, double-blind, placebo-controlled, randomized trial we investigated the efficacy of colchicine to reduce a composite of new-onset atrial fibrillation or atrioventricular conduction disturbances requiring the implantation of a permanent pacemaker at 30 days after TAVR. Between September 21, 2021 and April 25, 2024, 120 patients with aortic stenosis undergoing TAVR (mean age 80.6 ± 5 years, 64% male) were randomly allocated to treatment with colchicine (n = 60) or placebo (n = 60). The trial was prematurely stopped due to a higher rate of stroke in the experimental group in a pre-specified interim analysis (5 [8.3%] versus 0 at maximum available follow-up, p = 0.022). In the intention-to-treat population, the primary endpoint occurred in 6 patients (10%) in the colchicine group and in 15 patients (25%) in the placebo group (risk-difference -15.0%, 95% CI -28.3 to -1.7, p = 0.031). The prespecified imaging endpoint, subclinical leaflet thrombosis, was detected in 13 of 48 patients (27%) in the colchicine group versus 26 of 48 patients (54%) in the placebo group (risk difference -27.1%. 95% CI -46.0% to -8.2%, p = 0.007). Here, we show that periprocedural treatment with colchicine may reduce the incidence of new-onset arrhythmias and subclinical leaflet thrombosis after TAVR. However, given the premature termination of the trial due to an unexpected increase in the stroke rate among patients treated with colchicine, confirmatory trials are warranted to corroborate the effect of anti-inflammatory treatment on the incidence of arrhythmias and subclinical leaflet thrombosis after TAVR. The trial was an investigator-initiated study supported by dedicated grants from the Bangerter-Rhyner Foundation and the Swiss Life Foundation. ClinicalTrials.gov Identifier: NCT04870424.
2. Cardio-microcurrent device treatment for heart failure with reduced ejection fraction: Results from the C-MIC II open-label randomized controlled trial.
In non-ischemic HFrEF with LVEF 25–35% and NYHA III–IV, an implanted microcurrent generator added to GDMT improved LVEF by 5.1% at 6 months and significantly enhanced NYHA class, KCCQ scores, and 6-minute walk distance versus control. These results support bioelectronic therapy as a potential adjunct to medical therapy.
Impact: Provides randomized evidence that targeted microcurrent delivery can reverse adverse LV remodeling and improve patient-centered outcomes in advanced non-ischemic HFrEF.
Clinical Implications: If corroborated in larger, blinded, sham-controlled trials, microcurrent implants could become an adjunct option for symptomatic non-ischemic HFrEF with persistent dysfunction despite GDMT.
Key Findings
- LVEF improved by a mean 5.1% versus control at 6 months (95% CI 3.1–7.1; p<0.001).
- Higher proportions achieved ≥1 NYHA class improvement and ≥5-point KCCQ-OSS increase in the device group (both p<0.001).
- ≥30% increase in 6-minute walk distance was more frequent with the device (risk difference 38.3%; p<0.002).
Methodological Strengths
- Randomized controlled design with pre-specified functional and patient-reported endpoints
- Modified intention-to-treat analysis and clinically meaningful outcomes
Limitations
- Open-label design without sham control; small sample size
- Short follow-up (6 months); safety profile and durability need further study
Future Directions: Undertake multicentre, sham-controlled, blinded RCTs to validate efficacy, define mechanisms (electro-kinetics, edema resolution), and quantify safety and device-related adverse events over longer follow-up.
AIMS: In patients with heart failure, alterations in electrical fields generated within the myocardium have been associated with myocardial oedema which can act as a substrate for left ventricular dysfunction. Safety and efficacy of a direct microcurrent therapy using an implanted generator (C-MIC) remain uncertain. METHODS AND RESULTS: Ambulatory patients with non-ischaemic dilated cardiomyopathy with left ventricular ejection fraction (LVEF) of 25% to 35% and New York Heart Association (NYHA) class III-IV were randomized to C-MIC (device) or control group in addition to guideline-directed medical therapy. The primary endpoint was change in LVEF at 6 months. Pre-specified secondary endpoints included 6-min walk distance (6MWD), Kansas City Cardiomyopathy Questionnaire overall summary score (KCCQ-OSS), and NYHA functional class. Of 70 patients randomized, 65 were included in modified intention-to-treat analysis (C-MIC device: n = 32; control: n = 33). At 6 months, treatment with C-MIC versus control improved LVEF (mean difference: 5.1%; 95% confidence interval [CI] 3.1-7.1%, p < 0.001). The proportions of patients with improvement in at least one NYHA class (risk difference: 68.9%; 95% CI 50.6-87.2, p < 0.001), an increase of ≥5 points in KCCQ-OSS (risk difference: 60.0%; 95% CI 42.3-77.6, p < 0.001), and an increase of ≥30% in 6MWD (risk difference: 38.3%; 95% CI 14.4-62.2) were substantially higher in the device versus control group (p < 0.002). CONCLUSIONS: In patients with non-ischaemic chronic heart failure with reduced ejection fraction, the C-MIC device compared with control improved LVEF, symptoms, functional capacity and quality of life.
3. Computational modelling of myocardial metabolism in patients with advanced heart failure.
Proteomics-driven, patient-specific metabolic models revealed reduced ATP capacity and heterogeneous substrate preferences in advanced HF. The modeled fatty acid-to-glucose utilization ratio strongly predicted LV functional recovery after LVAD (C-index 0.94), nominating substrate manipulation (e.g., fatty acids, carnitine) as testable interventions.
Impact: Introduces a scalable systems approach linking myocardial proteomes to bioenergetic phenotypes and prognostic response, advancing precision cardiology for therapy guidance.
Clinical Implications: Personalized metabolic profiling may stratify HF patients for LVAD outcomes and identify candidates for substrate-targeted therapies (e.g., carnitine supplementation) pending prospective validation.
Key Findings
- Advanced HF patients showed reduced ATP production capacity versus controls (p<0.01) with substantial interindividual variability.
- Model-derived fatty acid-to-glucose utilization ratio predicted ≥10% LVEF improvement after LVAD with C-index 0.94 (p<0.01).
- Simulations suggested fatty acid administration and carnitine supplementation (in low mitochondrial carnitine) could restore substrate utilization.
Methodological Strengths
- Two independent cohorts with proteomics-based parameterization of personalized models
- External validation via prediction of LVAD response with high discrimination
Limitations
- Observational design; prospective interventional validation is lacking
- Biopsy-derived proteomics may limit generalizability and feasibility in routine care
Future Directions: Prospective trials testing substrate-targeted therapies guided by model phenotypes; evaluation of less invasive omics surrogates to enable broader clinical implementation.
AIMS: Perturbations of myocardial metabolism and energy depletion are well-established hallmarks of heart failure (HF), yet methods for their systematic assessment remain limited in humans. This study aimed to determine the ability of computational modelling of patient-specific myocardial metabolism to assess individual bioenergetic phenotypes and their clinical implications in HF. METHODS AND RESULTS: Based on proteomics-derived enzyme quantities in 136 cardiac biopsies, personalized computational models of myocardial metabolism were generated in two independent cohorts of advanced HF patients together with sex- and body mass index-matched non-failing controls. The bioenergetic impact of dynamic changes in substrate availability and myocardial workload were simulated, and the models' ability to predict the myocardial response following left ventricular assist device (LVAD) implantation was assessed. Compared to controls, HF patients had a reduced ATP production capacity (p < 0.01), although there was remarkable interindividual variance. Utilization of glucose relative to fatty acids was generally higher in HF patients, depending on substrate availability and myocardial workload. The ratio of fatty acid to glucose utilization was associated with reverse cardiac remodelling after LVAD implantation and highly predictive of an improvement in left ventricular ejection fraction ≥10% (C-index 0.94 [0.81-1.00], p < 0.01). System-level simulations identified fatty acid administration and carnitine supplementation in those with low mitochondrial carnitine content as potential pharmacological interventions to restore myocardial substrate utilization. CONCLUSIONS: Computational modelling identified a subset of advanced HF patients with preserved myocardial metabolism despite a similar degree of systolic dysfunction. Substrate preference was associated with the myocardial response after LVAD implantation, which suggests a role for substrate manipulation as a therapeutic approach. Computational assessment of myocardial metabolism in HF may improve understanding of disease heterogeneity, individual risk stratification, and guidance of personalized clinical decision-making in the future.