Daily Cardiology Research Analysis
Three impactful cardiology studies stood out: a Circulation mechanistic study identified PYGM as a cardioprotective node in myocardial infarction via enhanced glycogenolysis and autophagic flux; a JAMA Cardiology multicenter cohort showed His–ventricular (HV) interval on EPS outperforms ECG criteria for predicting major bradyarrhythmic events in myotonic dystrophy type 1; and a JAMA Cardiology Medicare analysis quantified the rising incidence and timing patterns of TAVR reinterventions, informin
Summary
Three impactful cardiology studies stood out: a Circulation mechanistic study identified PYGM as a cardioprotective node in myocardial infarction via enhanced glycogenolysis and autophagic flux; a JAMA Cardiology multicenter cohort showed His–ventricular (HV) interval on EPS outperforms ECG criteria for predicting major bradyarrhythmic events in myotonic dystrophy type 1; and a JAMA Cardiology Medicare analysis quantified the rising incidence and timing patterns of TAVR reinterventions, informing long-term valve strategies.
Research Themes
- Cardioprotective metabolism and autophagy in myocardial infarction
- Arrhythmic risk stratification using electrophysiological markers in neuromuscular disease
- Health services epidemiology of TAVR reinterventions and lifetime valve management
Selected Articles
1. PYGM Protects Against Myocardial Infarction by Enhancing Glycogenolysis and Facilitating Autophagic Flux.
In human MI samples and mouse MI models, PYGM levels fall, and loss of PYGM worsens infarct-related dysfunction and injury. Restoring PYGM enhances glycogenolysis, activates glycolysis/PPP, improves autophagic flux (partly via Thbs1 suppression), and mitigates oxidative stress, thereby preserving cardiac function.
Impact: This study identifies PYGM as a mechanistic cardioprotective lever linking glycogen metabolism to autophagy in MI, revealing a druggable pathway (PYGM–Thbs1–autophagy axis).
Clinical Implications: While preclinical, targeting glycogenolysis/autophagy via PYGM or Thbs1 could inspire novel acute MI therapies to limit injury and improve recovery.
Key Findings
- PYGM levels decreased in patients with MI and in infarcted mouse myocardium, correlating with impaired function.
- PYGM deficiency exacerbated MI-induced dysfunction and injury, whereas AAV-mediated PYGM replenishment reversed these effects.
- Mechanistically, PYGM enhanced glycogenolysis and activated glycolysis and PPP, reduced oxidative stress, improved autophagic flux, and downregulated Thbs1; blocking autophagy attenuated PYGM’s protection.
Methodological Strengths
- Integrated human sample analyses with in vivo genetic gain/loss-of-function mouse models
- Mechanistic dissection including metabolic pathway assays and autophagy modulation (genetic/pharmacologic)
Limitations
- Translation to humans remains unproven; no interventional human data
- Potential off-target or safety concerns of manipulating glycogenolysis/autophagy not assessed clinically
Future Directions: Test PYGM/Thbs1-targeted strategies in large animal MI models and early-phase human studies; develop small molecules or gene therapies to modulate the PYGM–autophagy axis.
BACKGROUND: PYGM (muscle glycogen phosphorylase), the rate-limiting enzyme in glycogenolysis, plays an indispensable role in maintaining cardiac energy metabolism. However, the role of PYGM in the pathogenesis of myocardial infarction (MI) remains unclear. METHODS: The expression profiles of PYGM in cardiac tissues and plasma samples from subjects with MI were assessed using immunoblotting. The role of PYGM in MI was determined by evaluating the effects of PYGM deficiency and its replenishment through adeno-associated virus-mediated PYGM expression in mice with MI. RESULTS: We found that circulating PYGM levels and their cardiac contents were significantly decreased in patients with MI, which was associated with impaired cardiac function. Loss of PYGM significantly exacerbated MI-induced cardiac dysfunction and damage in mice, and replenishment of PYGM profoundly reversed these adverse effects. Mechanistically, PYGM enhanced glycogenolysis by activating glycolysis and the pentose phosphate pathway, thereby improving cardiac energy homeostasis and mitigating oxidative stress. In addition, PYGM improved MI-induced autophagic flux obstacles and alleviated MI-induced cardiac damage by suppressing the expression of Thbs1 (thrombospondin-1). Moreover, genetic deficiency or pharmacological blockage of autophagy attenuated the protective effects of PYGM against MI-induced cardiac injury, and cardiac-specific knockdown of Thbs1 substantially improved the adverse impact of MI on cardiac dysfunction and damage in PYGM-null mice. CONCLUSIONS: PYGM safeguards against MI-induced myocardial injury by stimulating glycogenolysis and promoting autophagic flux, thus preserving myocardial energy homeostasis.
2. Electrocardiogram vs Electrophysiological Study and Major Conduction Delays in Myotonic Dystrophy Type 1.
Among 706 adults with DM1 followed for a median of 5.9 years, the HV interval was the strongest predictor of major bradyarrhythmic events, outperforming ECG-based PR/QRS criteria. An HV threshold of ≥65 ms further improved sensitivity and reclassification for identifying patients who may benefit from prophylactic pacing.
Impact: This refines current guideline thresholds by demonstrating superior prognostic utility of EPS-derived HV interval and supports a lower HV threshold to better capture high-risk patients.
Clinical Implications: EPS with HV interval assessment should be prioritized for risk stratification in DM1, and a threshold of ≥65 ms may be considered to guide prophylactic pacemaker decisions.
Key Findings
- In multivariable models, HV interval (per unit increase) was significantly associated with MBAEs, whereas PR/QRS ECG criteria were not.
- EPS-based criterion had higher reliability (HR 2.89 vs 1.95) and sensitivity (68.35% vs 34.76%) than ECG-based criteria; 28.8% of MBAE patients were accurately reclassified.
- Lowering HV threshold to ≥65 ms improved sensitivity to 90.18% and improved net reclassification by 33.7%.
Methodological Strengths
- Large multicenter registry with long median follow-up
- Robust statistical approach including joint models and assessment of time-varying covariates
Limitations
- Retrospective cohort design may introduce selection bias
- Generalizability beyond French tertiary centers and device-era changes may limit applicability
Future Directions: Prospective validation of HV ≥65 ms threshold and integration into decision algorithms; evaluate outcomes of pacing strategies guided by EPS in randomized or pragmatic trials.
IMPORTANCE: For the prevention of sudden cardiac death in myotonic dystrophy type 1 (dystrophia myotonica; DM1), professional practice guidelines recommend pacemaker implantation in asymptomatic patients with a PR interval greater than or equal to 240 milliseconds and/or QRS duration greater than or equal to 120 milliseconds on electrocardiogram (ECG), or a His-ventricular (HV) interval greater than or equal to 70 milliseconds during electrophysiological study (EPS), as class IIa indications. OBJECTIVE: To determine which of these strategies-ECG or EPS based-is more effective in predicting major bradyarrhythmic events (MBAEs). DESIGN, SETTING, AND PARTICIPANTS: This was a cohort analysis of retrospectively collected longitudinal data from the DM1 Heart Registry. The setting included cardiology and neurology departments of 6 French university hospitals. Study participants were selected from individuals enrolled in the DM1 Heart Registry between 2000 and 2020. The DM1 Heart Registry includes adults with genetically confirmed DM1. Included patients had a history of first EPS after 1999 and no personal history of advanced atrioventricular block or sustained ventricular tachycardia. Study data were analyzed from January to July 2025. EXPOSURES: ECG- and EPS-based strategies. MAIN OUTCOMES AND MEASURES: The primary outcome was MBAEs, defined as sudden cardiac death, resuscitated cardiac arrest, or second-degree type II or complete atrioventricular block. RESULTS: Of 1778 adults with genetically confirmed DM1 enrolled in the DM1 Heart Registry, a total of 706 patients (mean [SD] age, 42 [13] years; 359 male [51%]) were included in this study. At baseline, 273 patients (38%) had an HV interval greater than or equal to 70 milliseconds, and 232 (32%) met ECG criteria. Over a median (IQR) follow-up of 5.9 (2.3-9.7) years, 99 patients (14%) experienced an MBAE. In multivariable Cox and joint models incorporating baseline and time-varying values of PR and QRS durations, the HV interval was the only variable significantly associated with the incidence of MBAEs (hazard ratio [HR], 1.77; 95% CI, 1.46-2.16; P < .001 and HR, 1.78; 95% CI, 1.40-2.22; P = .001, respectively). Compared with ECG-based criteria, the EPS criterion proved to be a more reliable (HR, 2.89; 95% CI, 1.92-4.34 vs HR, 1.95; 95% CI, 1.31-2.89) and more sensitive (performance index [SE], 68.35% [6.24%] vs 34.76% [6.47%]) predictor of MBAE and accurately reclassified 28.8% of patients with an MBAE. Lowering the threshold to HV greater than or equal to 65 milliseconds further improved sensitivity (performance index [SE], 90.18% [3.85%]) and net reclassification improvement (33.7%; 95% CI, 19.6%-48.2%) for MBAE prediction. CONCLUSIONS AND RELEVANCE: In this cohort of patients with DM1, the HV interval outperformed ECG criteria in predicting MBAEs. An HV threshold greater than or equal to 65 milliseconds may enhance risk stratification for prophylactic pacing.
3. Contemporary Incidence and Procedural Volume of Transcatheter Aortic Valve Reintervention.
Using Medicare data (2012–2024), the study found increasing reintervention volumes: 2,374 redo TAVR and 1,346 TAVR explants after 410,720 index TAVRs, with annual incidence rising to 0.28% by 2023. Redo TAVR predominates beyond 5 years from index TAVR, highlighting evolving lifetime management.
Impact: Quantifies real-world reintervention patterns at scale, informing counseling, surveillance intervals, and procedural planning for lifetime valve management.
Clinical Implications: Programs should anticipate growing redo-TAVR volumes, especially beyond 5 years, optimize follow-up imaging, and develop algorithms to select redo TAVR vs explant vs SAVR.
Key Findings
- Among 410,720 TAVRs (2012–2024), 2,374 redo TAVRs and 1,346 TAVR explants were identified; annual reintervention incidence rose from 0.17% (2019) to 0.28% (2023).
- Redo TAVR was most common within 3 months after index TAVR (17.3%), whereas explant peaked at 1–2 years (19.2%); beyond 5 years, redo TAVR predominated (88.5%).
- Valve-in-valve TAVR (after SAVR) and redo SAVR volumes contextualize broader reintervention trends in aortic valve replacement.
Methodological Strengths
- Nationwide claims analysis with very large denominator and longitudinal span
- Clear operational definitions for reintervention categories and time-interval analyses
Limitations
- Claims-based retrospective design susceptible to coding errors and limited clinical granularity
- Incidence estimates may not generalize beyond Medicare population or to non-U.S. systems
Future Directions: Link procedural patterns to patient-level outcomes to define optimal redo strategies; assess durability by valve type and anatomy; model lifetime management pathways.
IMPORTANCE: Transcatheter aortic valve replacement (TAVR) reintervention is performed by either redo TAVR or TAVR explant. There is insufficient data on contemporary TAVR reintervention procedural incidence and volume. OBJECTIVE: To evaluate contemporary procedural volumes of redo TAVR and TAVR explant. DESIGN, SETTING, AND PARTICIPANTS: This retrospective analysis of redo TAVR and TAVR explant annual incidence and procedural volume was performed from January 2012 to June 2024. For comprehensive assessment of aortic valve replacement, analysis of SAVR reintervention annual incidence and procedural volume was also performed. Data were obtained through the US Centers for Medicare & Medicaid Services Virtual Research Data Center. Patients with prior TAVR or SAVR who underwent subsequent TAVR or SAVR were included. EXPOSURES: Patients who underwent a TAVR after TAVR defined the redo TAVR group, while patients who underwent SAVR after TAVR defined the TAVR explant group. Patients who underwent a TAVR after SAVR defined the valve-in-valve (ViV) TAVR group, while patients who underwent SAVR after SAVR defined the redo SAVR group. Analysis of annual incidences and procedural volumes of all groups at different time intervals was conducted. MAIN OUTCOMES AND MEASURES: The primary outcome was annual incidence and procedural volume of both redo TAVR and TAVR explant. The secondary outcome was annual incidence and procedural volume of both ViV TAVR and redo SAVR. RESULTS: Of 410 720 total TAVRs from 2012 to 2024, 2374 redo TAVRs and 1346 TAVR explants were identified. Of 299 780 total SAVRs from 2012 to 2024, 5044 ViV-TAVRs and 4202 redo SAVRs were identified. Since 2020, there have been 1518 redo TAVRs and 1007 TAVR explants. The annual incidence of TAVR reintervention has changed from 0.17% in 2019 to 0.28% in 2023. Although the most common time interval for redo TAVR after index TAVR was within 3 months (410 of 2374 [17.3%]) and for TAVR explant after index TAVR was 1 to 2 years (259 of 1346 [19.2%]), redo TAVR was the predominant procedure beyond 5 years from the index TAVR (725 of 819 [88.5%]). CONCLUSIONS AND RELEVANCE: In this study, annual volumes of both redo TAVR and TAVR explant continued to increase, particularly in recent years. Redo TAVR is frequently performed over 5 years from the index TAVR. Future analysis to determine the appropriate TAVR reintervention strategy for individual patients is needed.