Daily Cardiology Research Analysis
Today’s top cardiology research spans translational innovation, imaging‑driven risk stratification, and metabolic prevention after myocardial infarction. A new red‑light opsin (ChReef) enables efficient, sustained optogenetic control of cardiomyocytes, while a CMR‑based score (DERIVATE Risk Score 2.0) markedly improves arrhythmic risk prediction in non‑ischaemic cardiomyopathy, and dapagliflozin reduces new‑onset type 2 diabetes after MI across glycaemic and BMI strata.
Summary
Today’s top cardiology research spans translational innovation, imaging‑driven risk stratification, and metabolic prevention after myocardial infarction. A new red‑light opsin (ChReef) enables efficient, sustained optogenetic control of cardiomyocytes, while a CMR‑based score (DERIVATE Risk Score 2.0) markedly improves arrhythmic risk prediction in non‑ischaemic cardiomyopathy, and dapagliflozin reduces new‑onset type 2 diabetes after MI across glycaemic and BMI strata.
Research Themes
- Bioelectronic/optogenetic therapeutics for cardiac control
- CMR-based risk stratification in non-ischaemic cardiomyopathy
- SGLT2 inhibition to prevent new-onset diabetes after MI
Selected Articles
1. Efficient and sustained optogenetic control of sensory and cardiac systems.
The authors engineer ChReef, a red-shifted opsin with minimal desensitization and fast closure that achieves stable, low-light optogenetic pacing and depolarization block in cardiomyocyte clusters. AAV delivery to retinal ganglion cells restores vision in blind mice under weak illumination, and nanojoule-threshold auditory pathway activation is demonstrated in rodents and non-human primates, supporting LED-based optical cochlear implants.
Impact: This work provides a broadly applicable optogenetic actuator that enables efficient cardiac pacing at low irradiance and cross-system sensory restoration, opening avenues for non-electrical bioelectronic therapies.
Clinical Implications: While preclinical, ChReef suggests a future route to light-based cardiac pacing/defibrillation and sensory neuroprosthetics with potentially reduced energy, improved spatial selectivity, and minimized tissue heating compared with electrical approaches.
Key Findings
- Engineered opsin ChReef showed minimal photocurrent desensitization, unitary conductance ~80 fS, and ~30 ms closing kinetics enabling reliable low‑light control.
- Red‑light optical pacing and depolarization block were achieved in ChReef‑expressing cardiomyocyte clusters.
- AAV‑mediated ChReef expression in retinal ganglion cells restored visual function in blind mice under very low illumination (e.g., tablet screen).
- Auditory pathway stimulation at nanojoule thresholds was demonstrated in rodents and non‑human primates, supporting LED‑based optical cochlear implants.
Methodological Strengths
- Cross-system validation (cardiac, visual, auditory) including rodent and non-human primate models
- Robust biophysical characterization (desensitization, conductance, kinetics) and in situ AAV gene delivery
Limitations
- Preclinical proof‑of‑concept without long‑term safety or arrhythmia efficacy testing in large‑animal hearts
- Clinical translation depends on safe gene delivery, immunogenicity control, and optical energy delivery strategies
Future Directions: Evaluate long‑term cardiac safety and efficacy in large‑animal arrhythmia models, optimize delivery (AAV serotypes, promoters) and light hardware, and compare against electrical pacing in energy, selectivity, and tissue effects.
Optogenetic control is used to manipulate the activity of specific cell types in vivo for a variety of biological and clinical applications. Here we report ChReef, an improved variant of the channelrhodopsin ChRmine. ChReef offers minimal photocurrent desensitization, a unitary conductance of 80 fS and closing kinetics of 30 ms, which together enable reliable optogenetic control of cells at low light levels with good temporal fidelity and sustained stimulation. We demonstrate efficient and reliable red-light pacing and depolarization block of ChReef-expressing cardiomyocyte clusters. We used adeno-associated-virus-based gene transfer to express ChReef in retinal ganglion cells, where it restores visual function in blind mice with light sources as weak as an iPad screen. Toward optogenetic hearing restoration, ChReef enables stimulation of the auditory pathway in rodents and non-human primates with nanojoule thresholds, enabling efficient and frequency-specific stimulation by LED-based optical cochlear implants.
2. Redefining the risk of major arrhythmic events in non-ischaemic cardiomyopathy: insights from the DERIVATE-NICM study.
In 1,384 NICM patients, midwall LGE presence and scar location independently predicted major arrhythmic events. The multi‑parametric DERIVATE Risk Score 2.0, incorporating LGE pattern distribution, substantially improved risk reclassification over LVEF and the prior DERIVATE 1.0, with findings validated in an external cohort.
Impact: This study operationalizes CMR scar patterns into a validated, clinically applicable risk score that outperforms EF‑based selection for primary prevention ICD in NICM.
Clinical Implications: CMR‑guided risk stratification beyond LVEF (considering midwall LGE presence and location) should inform ICD candidacy in NICM and may reduce under‑/over‑treatment.
Key Findings
- Among 1,384 NICM patients (median follow‑up 959 days), MAACE occurred in 9.2%.
- Independent predictors: male sex (HR 1.605), lower LVEF per % (HR 0.977), and midwall LGE presence/location (weighted HR 1.066; all significant).
- DERIVATE Risk Score 2.0 achieved a net reclassification improvement of 54.52% vs. LVEF 35% cut‑off and outperformed DERIVATE 1.0; results were validated in a separate cohort.
Methodological Strengths
- Large cohort with external validation and multi‑parametric CMR integration
- Robust multivariable modelling and net reclassification improvement analysis
Limitations
- Observational registry design with potential residual confounding
- CMR acquisition/interpretation variability across centers may affect generalizability
Future Directions: Prospective implementation studies to test DERIVATE 2.0‑guided ICD strategies versus standard care, and integration with genetic and electroanatomic markers to further refine risk.
AIMS: Selection of the patients for implantable cardioverter defibrillator primary prevention therapy in non-ischaemic cardiomyopathy (NICM) needs to be improved. To evaluate the additional prognostic value of a new cardiac magnetic resonance (CMR) score based on late gadolinium enhancement (LGE) pattern distribution (DERIVATE Risk Score 2.0) when compared with previously published DERIVATE Risk Score 1.0, which is based solely on quantitative parameters, in a cohort of NICM patients enrolled in the DERIVATE registry. METHODS AND RESULTS: One thousand three hundred and eighty-four NICM patients with chronic heart failure and left ventricular ejection fraction (LVEF) < 50% were evaluated for primary sudden cardiac death prevention therapy. Major adverse arrhythmic cardiac events (MAACEs) were the primary endpoint. During a median follow-up of 959 days, MAACE occurred in 128 (9.2%) patients. In the multivariate analyses, male gender [hazard ratio (HR): 1.605 (95% confidence interval, CI: 1.051-2.451); P = 0.028], LVEF per point % [HR: 0.977 (95% CI: 0.961-0.993); P = 0.005] and presence and location of midwall LGE [weighted HR: 1.066 (95% CI: 1.045-1.086), P < 0.001] were independent predictors of MAACE. A multi-parametric CMR-weighted predictive-derived score (DERIVATE Risk Score 2.0) provided a higher additional prognostic value vs. transthoracic echocardiography-LVEF cut-off of 35% when compared with the previous published DERIVATE Risk Score 1.0 with a net reclassification improvement of 54.52% (95% CI: 36.52-72.52%; P < 0.001). These findings were confirmed in the validation cohort. CONCLUSION: The presence of midwall LGE, but also the location of scar, confers an added and independent MAACE risk to a large NICM population influencing the choice of treatment.
3. Impact of Dapagliflozin on Cardiometabolic Outcomes After Acute Myocardial Infarction According to Baseline Glycemic Status and Body Mass Index: Subanalyses of the DAPA-MI Trial.
In 3,425 DAPA‑MI participants without prior T2DM, dapagliflozin reduced new‑onset diabetes after MI both in normoglycemia (HR 0.40; trend) and prediabetes (HR 0.74; significant), irrespective of BMI category. Heart failure symptom benefit was greater in prediabetes than in normoglycemia.
Impact: These data extend SGLT2 inhibitor benefits to prevention of incident T2DM after MI across glycaemic and BMI strata, supporting early post‑MI initiation even in non‑diabetic patients.
Clinical Implications: Consider initiating dapagliflozin early after MI in eligible patients without T2DM to reduce diabetes incidence and improve symptoms, while continuing standard secondary prevention.
Key Findings
- In normoglycemia (n=1,926), new‑onset T2DM was 0.6% with dapagliflozin vs 1.6% with placebo (HR 0.40; 95% CI 0.15–1.03).
- In prediabetes (n=1,499), new‑onset T2DM was 10.1% vs 13.1% (HR 0.74; 95% CI 0.55–0.99).
- Benefits were consistent across BMI strata (<25, 25–<30, ≥30 kg/m²) and HF symptom burden improved more in prediabetes.
Methodological Strengths
- Randomized, placebo‑controlled parent trial with prespecified subgrouping by HbA1c and BMI
- Clinically meaningful endpoints (incident T2DM, symptom burden) and large sample
Limitations
- Subanalysis; not powered for hard cardiovascular outcomes by subgroups
- Exclusion of patients with established T2DM limits generalizability to broader MI populations
Future Directions: Assess durability of diabetes prevention, impact on micro/macrovascular outcomes, and cost‑effectiveness of early post‑MI SGLT2i in non‑diabetic populations.
BACKGROUND: Dapagliflozin improved cardiometabolic outcomes following myocardial infarction in patients without prior type-2 diabetes (T2DM) in the DAPA-MI (dapagliflozin in patients with myocardial infarction) trial. The effect of glycemic status and body mass index (BMI) post-myocardial infarction requires elucidation. METHODS: Participants with T2DM diagnosis, without baseline hemoglobin A1c, or not receiving any study medication, were excluded. Eligible participants were categorized, according to baseline hemoglobin A1c, as normoglycemic (<5.7% [39 mmol/mol]) or prediabetes (5.7 to <6.5% [48 mmol/mol]) and according to baseline BMI (<25, 25 to <30, and ≥30 kg/m RESULTS: Of 4017 DAPA-MI participants, 3425 were eligible. In 1926 with baseline normoglycemia, new-onset T2DM occurred in 0.6% and 1.6% assigned to dapagliflozin and placebo, respectively (hazard ratio, 0.40 [95% CI, 0.15-1.03]); in 1499 with prediabetes at baseline, new-onset T2DM occurred in 10.1% and 13.1%, respectively (hazard ratio, 0.74 [05% CI, 0.55-0.99]; CONCLUSIONS: Dapagliflozin reduced the occurrence of new-onset T2DM following myocardial infarction, regardless of baseline hemoglobin A1c or BMI. Dapagliflozin provided greater reduction in heart failure symptom burden in those with prediabetes compared with normoglycemia.