<p>We read with great interest the observational study by Meunier et al. evaluating a stent-less strategy using drug-coated balloons (DCB) in coronary artery disease (CAD) [<span>1</span>]. The present single-center observational study evaluating the long-term effectiveness of a stent-less strategy with DCB angioplasty in CAD undoubtedly adds to the literature regarding contemporary percutaneous coronary intervention (PCI) [<span>1</span>]. Nevertheless, methodological limitations remain that could impact the reliability and generalizability of the findings, which were not fully addressed in the manuscript. Most critically, the absence of randomization and reliance on operator discretion for allocating stent-less versus bailout drug-eluting stent (DES) strategies raises concerns regarding selection bias and confounding. Randomized controlled trials (RCTs) such as BASKET-SMALL 2 and PICCOLETO II have demonstrated the importance of random allocation in minimizing selection bias and ensuring comparability across intervention arms, thereby providing more robust estimates of relative effectiveness between DCB and DES strategies [<span>2, 3</span>]. Employing a multicenter randomized design, as recommended in recent consensus statements, would also enhance external validity and facilitate application to broader clinical practice [<span>4, 5</span>]. Another key limitation relates to the lack of core laboratory adjudication and systematic use of intravascular imaging for lesion assessment and procedural outcome validation. RCTs and multicenter DCB registries increasingly mandate independent angiographic review and intravascular imaging such as OCT or IVUS to rigorously evaluate lesion morphology, residual stenosis, and dissection severity [<span>4</span>]. Studies have shown that core lab adjudication substantially reduces inter-observer variability and measurement bias, thereby improving endpoint ascertainment and clinical trial integrity [<span>5, 6</span>]. Furthermore, the manuscript provides insufficient detail regarding standardization and stratification of concomitant antiplatelet therapy, which may have influenced outcome measurements such as major adverse cardiac events and bleeding rates. The heterogeneity in antiplatelet regimens was noted but not adjusted for in the primary analyses. Recent RCTs including TWILIGHT and TICO have demonstrated that clearly defined, protocolized antiplatelet regimens and stratified reporting are essential for interpreting ischemic and bleeding risk profiles in PCI populations [<span>7, 8</span>]. To address these limitations, future studies should prioritize multicenter RCT designs with independent core laboratory angiographic adjudication and routine use of contemporary intravascular imaging. Endpoints must be standardized according to consensus definitions, with adjustment for confounders including antiplatelet therapy regimens, in line with recommendations from leading international PCI trials and expert stat
{"title":"Advancing the Design of Observational Studies in Drug-Coated Balloon Angioplasty: Bridging Practice With Evidence-Based Standards","authors":"Kunal Mahajan, Jaibharat Sharma, Surender Himral, Vivek Rana, Shekhar Vohra","doi":"10.1002/clc.70238","DOIUrl":"10.1002/clc.70238","url":null,"abstract":"<p>We read with great interest the observational study by Meunier et al. evaluating a stent-less strategy using drug-coated balloons (DCB) in coronary artery disease (CAD) [<span>1</span>]. The present single-center observational study evaluating the long-term effectiveness of a stent-less strategy with DCB angioplasty in CAD undoubtedly adds to the literature regarding contemporary percutaneous coronary intervention (PCI) [<span>1</span>]. Nevertheless, methodological limitations remain that could impact the reliability and generalizability of the findings, which were not fully addressed in the manuscript. Most critically, the absence of randomization and reliance on operator discretion for allocating stent-less versus bailout drug-eluting stent (DES) strategies raises concerns regarding selection bias and confounding. Randomized controlled trials (RCTs) such as BASKET-SMALL 2 and PICCOLETO II have demonstrated the importance of random allocation in minimizing selection bias and ensuring comparability across intervention arms, thereby providing more robust estimates of relative effectiveness between DCB and DES strategies [<span>2, 3</span>]. Employing a multicenter randomized design, as recommended in recent consensus statements, would also enhance external validity and facilitate application to broader clinical practice [<span>4, 5</span>]. Another key limitation relates to the lack of core laboratory adjudication and systematic use of intravascular imaging for lesion assessment and procedural outcome validation. RCTs and multicenter DCB registries increasingly mandate independent angiographic review and intravascular imaging such as OCT or IVUS to rigorously evaluate lesion morphology, residual stenosis, and dissection severity [<span>4</span>]. Studies have shown that core lab adjudication substantially reduces inter-observer variability and measurement bias, thereby improving endpoint ascertainment and clinical trial integrity [<span>5, 6</span>]. Furthermore, the manuscript provides insufficient detail regarding standardization and stratification of concomitant antiplatelet therapy, which may have influenced outcome measurements such as major adverse cardiac events and bleeding rates. The heterogeneity in antiplatelet regimens was noted but not adjusted for in the primary analyses. Recent RCTs including TWILIGHT and TICO have demonstrated that clearly defined, protocolized antiplatelet regimens and stratified reporting are essential for interpreting ischemic and bleeding risk profiles in PCI populations [<span>7, 8</span>]. To address these limitations, future studies should prioritize multicenter RCT designs with independent core laboratory angiographic adjudication and routine use of contemporary intravascular imaging. Endpoints must be standardized according to consensus definitions, with adjustment for confounders including antiplatelet therapy regimens, in line with recommendations from leading international PCI trials and expert stat","PeriodicalId":10201,"journal":{"name":"Clinical Cardiology","volume":"48 12","pages":""},"PeriodicalIF":2.3,"publicationDate":"2025-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12703820/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145755361","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
<p>Sudden cardiac death (SCD) remains an unresolved issue even in the contemporary era of implantable cardioverter-defibrillator therapy (ICD), largely because of the difficulty in accurate risk prediction. The present study sought to identify clinical features of SCD victims with non-ischemic myocardial fibrosis [<span>1</span>]. The authors found that fragmented QRS complexes or a history of transient loss of consciousness (TLOC) were major characteristics of such patients. While this is an important contribution, several concerns arise.</p><p>Our group previously reported that the presence of a J-wave, reflecting repolarization abnormalities—similar to QT prolongation and T-wave inversion—was associated with ventricular fibrillation as the terminal electrocardiographic event [<span>2</span>]. Conversely, a fragmented QRS represents an abnormality of depolarization rather than repolarization. In the present study, were the terminal electrocardiograms (ECGs) of SCD victims with fragmented QRS more commonly asystole or pulseless electrical activity rather than ventricular fibrillation? How do the authors interpret the relationship between different types of polarization abnormalities and the final rhythm observed? Clarifying this relationship would be crucial for risk stratification and further pathophysiological understanding.</p><p>Another concern lies in the limited availability of clinical data. Only 28% of victims had ECGs available, and merely 11% had both ECG and medical history [<span>1</span>]. Such a restricted dataset raises the possibility of selection bias and questions the generalizability of the findings. Moreover, TLOC, although frequent, is not necessarily of cardiac origin. Without detailed adjudication, including differentiation from neurological or reflex-mediated causes, the specificity of this marker as an indicator of impending SCD remains uncertain.</p><p>The pathophysiological link between fragmented QRS and myocardial fibrosis was also insufficiently addressed [<span>1</span>]. Prior studies have demonstrated that fragmented QRS may reflect impaired conduction due to localized scar or interstitial fibrosis, and that it correlates with abnormal global longitudinal strain [<span>3</span>]. Moreover, fragmented QRS is also associated with arrhythmic events in other entities such as Brugada syndrome. However, whether fragmented QRS in the setting of primary myocardial fibrosis is merely a surrogate of structural remodeling or a direct arrhythmogenic substrate remains unanswered.</p><p>It should also be emphasized that the features highlighted in this study—fragmented QRS and TLOC—are neither novel nor specific to primary myocardial fibrosis. Given that ICD implantation cannot be justified in all individuals with these findings alone, we believe these markers should be integrated into a broader, multi-modal risk stratification strategy. Cardiac magnetic resonance imaging to detect diffuse or patchy fibrosis, genetic testing f
{"title":"Detailed Association Between Electrocardiogram Abnormality and Primary Myocardial Fibrosis","authors":"Yu Nomoto, Naoya Kataoka, Teruhiko Imamura","doi":"10.1002/clc.70237","DOIUrl":"10.1002/clc.70237","url":null,"abstract":"<p>Sudden cardiac death (SCD) remains an unresolved issue even in the contemporary era of implantable cardioverter-defibrillator therapy (ICD), largely because of the difficulty in accurate risk prediction. The present study sought to identify clinical features of SCD victims with non-ischemic myocardial fibrosis [<span>1</span>]. The authors found that fragmented QRS complexes or a history of transient loss of consciousness (TLOC) were major characteristics of such patients. While this is an important contribution, several concerns arise.</p><p>Our group previously reported that the presence of a J-wave, reflecting repolarization abnormalities—similar to QT prolongation and T-wave inversion—was associated with ventricular fibrillation as the terminal electrocardiographic event [<span>2</span>]. Conversely, a fragmented QRS represents an abnormality of depolarization rather than repolarization. In the present study, were the terminal electrocardiograms (ECGs) of SCD victims with fragmented QRS more commonly asystole or pulseless electrical activity rather than ventricular fibrillation? How do the authors interpret the relationship between different types of polarization abnormalities and the final rhythm observed? Clarifying this relationship would be crucial for risk stratification and further pathophysiological understanding.</p><p>Another concern lies in the limited availability of clinical data. Only 28% of victims had ECGs available, and merely 11% had both ECG and medical history [<span>1</span>]. Such a restricted dataset raises the possibility of selection bias and questions the generalizability of the findings. Moreover, TLOC, although frequent, is not necessarily of cardiac origin. Without detailed adjudication, including differentiation from neurological or reflex-mediated causes, the specificity of this marker as an indicator of impending SCD remains uncertain.</p><p>The pathophysiological link between fragmented QRS and myocardial fibrosis was also insufficiently addressed [<span>1</span>]. Prior studies have demonstrated that fragmented QRS may reflect impaired conduction due to localized scar or interstitial fibrosis, and that it correlates with abnormal global longitudinal strain [<span>3</span>]. Moreover, fragmented QRS is also associated with arrhythmic events in other entities such as Brugada syndrome. However, whether fragmented QRS in the setting of primary myocardial fibrosis is merely a surrogate of structural remodeling or a direct arrhythmogenic substrate remains unanswered.</p><p>It should also be emphasized that the features highlighted in this study—fragmented QRS and TLOC—are neither novel nor specific to primary myocardial fibrosis. Given that ICD implantation cannot be justified in all individuals with these findings alone, we believe these markers should be integrated into a broader, multi-modal risk stratification strategy. Cardiac magnetic resonance imaging to detect diffuse or patchy fibrosis, genetic testing f","PeriodicalId":10201,"journal":{"name":"Clinical Cardiology","volume":"48 12","pages":""},"PeriodicalIF":2.3,"publicationDate":"2025-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12703648/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145755352","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Mushood Ahmed, Muhammad Burhan, Aimen Shafiq, Tallal Mushtaq Hashmi, Raheel Ahmed, Marat Fudim, Robert J. Mentz, Gregg C. Fonarow
This comprehensive meta-analysis reveals that GLP-1 and dual GLP-1/GIP receptor agonists are associated with reduced risk of composite cardiovascular endpoints and worsening heart failure events. However, no statistically significant differences were observed regarding all-cause or cardiovascular mortality.