Pub Date : 2025-12-01DOI: 10.1016/j.jcmg.2025.07.016
Sebastiaan Dhont MD , Wouter L'Hoyes MD , Sara Moura Ferreira MD , Pieter Martens MD, Msc, PhD , Jan Stassen MD , Guido Claessen MD, PhD , Sarah Stroobants MD , Siddharth Jogani MD , Ruta Jasaityte MD, PhD , Lieven Herbots MD, PhD , Jan Verwerft MD , Philippe B. Bertrand MD, PhD
Background
Atrial functional mitral regurgitation (AFMR) is prevalent among patients with heart failure with preserved ejection fraction (HFpEF) and associated with adverse outcome, yet this bidirectional association remains underexplored.
Objectives
The purpose of this study was to elucidate the pathophysiological and prognostic significance of AFMR in HFpEF, both at rest and during exercise.
Methods
In this multicenter cohort study, consecutive patients with HFpEF underwent cardiopulmonary exercise testing with echocardiography, with a particular focus on mitral regurgitation (MR) severity assessment in rest and during exercise. Longitudinal follow-up included cardiovascular hospitalizations and all-cause mortality.
Results
The study involved 429 patients with HFpEF (age 74 ± 8 years, 65% female). AFMR was observed in 35% of patients at rest (24% mild, 11% ≥ moderate). Increasing AFMR severity correlated with atrial fibrillation, larger left atrium volumes, reduced left atrial function, lower peak oxygen consumption, and increased exercise-induced pulmonary hypertension. After adjusting for age, sex, ventricular and atrial volume and function, moderate or severe MR remained linked with worse outcomes (HR: 4.03; 95% CI: 2.26-7.21; P < 0.001). During exercise, MR severity increased in 12% of patients based on guideline-based thresholds. Notably, even in patients without formal reclassification, an absolute increase in effective regurgitant orifice area ≥5 mm2 during exercise was independently predictive of adverse outcomes (HR: 2.43; 95% CI 1.34-4.41; P = 0.004). This increase was not related to systemic blood pressure, chronotropic incompetence, or left ventricular dysfunction.
Conclusions
AFMR is common in HFpEF and independently associated with adverse outcomes when moderate or severe at rest. Even mild, exercise-induced increases carry additional prognostic value, underscoring the relevance of both resting and dynamic AFMR assessment.
背景：心房功能性二尖瓣反流（AFMR）在保留射血分数（HFpEF）的心力衰竭患者中普遍存在，并与不良结局相关，但这种双向关联仍未得到充分探讨。目的：本研究的目的是阐明静息和运动时AFMR在HFpEF中的病理生理和预后意义。方法：在这项多中心队列研究中，连续的HFpEF患者通过超声心动图进行心肺运动试验，特别关注休息和运动期间二尖瓣反流（MR）严重程度的评估。纵向随访包括心血管住院和全因死亡率。结果：本研究纳入429例HFpEF患者（年龄74±8岁，65%为女性）。35%的患者在休息时观察到AFMR（24%轻度，11%≥中度）。AFMR严重程度的增加与心房颤动、左心房容量增大、左心房功能降低、峰值耗氧量降低和运动性肺动脉高压升高相关。在调整了年龄、性别、心室和心房容积和功能后，中度或重度MR仍然与较差的结果相关（HR: 4.03; 95% CI: 2.26-7.21; P < 0.001）。在运动期间，基于指南的阈值，12%的患者MR严重程度增加。值得注意的是，即使在没有正式重新分类的患者中，运动期间有效反流口面积≥5 mm2的绝对增加也是不良结局的独立预测因素（HR: 2.43; 95% CI 1.34-4.41; P = 0.004）。这种增加与全身血压、变时功能不全或左心室功能不全无关。结论：AFMR在HFpEF中很常见，并且在休息时与中度或重度不良结局独立相关。即使是轻微的运动引起的增加也具有额外的预后价值，强调静息和动态AFMR评估的相关性。
{"title":"Atrial Functional Mitral Regurgitation and Exercise-Induced Changes in Heart Failure With Preserved Ejection Fraction","authors":"Sebastiaan Dhont MD , Wouter L'Hoyes MD , Sara Moura Ferreira MD , Pieter Martens MD, Msc, PhD , Jan Stassen MD , Guido Claessen MD, PhD , Sarah Stroobants MD , Siddharth Jogani MD , Ruta Jasaityte MD, PhD , Lieven Herbots MD, PhD , Jan Verwerft MD , Philippe B. Bertrand MD, PhD","doi":"10.1016/j.jcmg.2025.07.016","DOIUrl":"10.1016/j.jcmg.2025.07.016","url":null,"abstract":"<div><h3>Background</h3><div>Atrial functional mitral regurgitation (AFMR) is prevalent among patients with heart failure with preserved ejection fraction (HFpEF) and associated with adverse outcome, yet this bidirectional association remains underexplored.</div></div><div><h3>Objectives</h3><div>The purpose of this study was to elucidate the pathophysiological and prognostic significance of AFMR in HFpEF, both at rest and during exercise.</div></div><div><h3>Methods</h3><div>In this multicenter cohort study, consecutive patients with HFpEF underwent cardiopulmonary exercise testing with echocardiography, with a particular focus on mitral regurgitation (MR) severity assessment in rest and during exercise. Longitudinal follow-up included cardiovascular hospitalizations and all-cause mortality.</div></div><div><h3>Results</h3><div>The study involved 429 patients with HFpEF (age 74 ± 8 years, 65% female). AFMR was observed in 35% of patients at rest (24% mild, 11% ≥ moderate). Increasing AFMR severity correlated with atrial fibrillation, larger left atrium volumes, reduced left atrial function, lower peak oxygen consumption, and increased exercise-induced pulmonary hypertension. After adjusting for age, sex, ventricular and atrial volume and function, moderate or severe MR remained linked with worse outcomes (HR: 4.03; 95% CI: 2.26-7.21; <em>P</em> < 0.001). During exercise, MR severity increased in 12% of patients based on guideline-based thresholds. Notably, even in patients without formal reclassification, an absolute increase in effective regurgitant orifice area ≥5 mm<sup>2</sup> during exercise was independently predictive of adverse outcomes (HR: 2.43; 95% CI 1.34-4.41; <em>P</em> = 0.004). This increase was not related to systemic blood pressure, chronotropic incompetence, or left ventricular dysfunction.</div></div><div><h3>Conclusions</h3><div>AFMR is common in HFpEF and independently associated with adverse outcomes when moderate or severe at rest. Even mild, exercise-induced increases carry additional prognostic value, underscoring the relevance of both resting and dynamic AFMR assessment.</div></div>","PeriodicalId":14767,"journal":{"name":"JACC. Cardiovascular imaging","volume":"18 12","pages":"Pages 1285-1296"},"PeriodicalIF":15.2,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145023386","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-01DOI: 10.1016/j.jcmg.2025.07.019
Milind Y. Desai MD, MBA , Yuichiro Okushi MD , Kathy Wolski MPH , Jeffrey B. Geske MD , Anjali Tiku Owens MD , Qiuqing Wang MPH , Sara Saberi MS, MD , Andrew Wang MD , Paul Cremer MS, MD , Neal K. Lakdawala MD , Mark V. Sherrid MD , Albree Tower-Rader MD , David R. Fermin MD , Mark A. Zenker MD , Srihari S. Naidu MD , Kathy Lampl MD , Steven E. Nissen MD , Zoran Popovic MD, MPH
Background
In the VALOR-HCM (A Study to Evaluate Mavacamten in Adults With Symptomatic Obstructive HCM Who Are Eligible for Septal Reduction Therapy; NCT04349072) trial, patients with severely symptomatic obstructive hypertrophic cardiomyopathy (HCM) treated with mavacamten demonstrated significant improvement in left ventricular outflow tract (LVOT) gradients and echocardiographic indices of cardiac remodeling in the short term.
Objectives
The authors sought to assess whether mavacamten results in sustained favorable long-term cardiac remodeling at 128 weeks (end of trial).
Methods
A total of 112 adult symptomatic obstructive HCM patients (mean age: 60.3 years; 50% men; and 94% NYHA functional class III/IV) who were referred for septal reduction therapy were randomized 1:1 to mavacamten or placebo for 16 weeks. Subsequently, placebo patients transitioned to and received 112 weeks of mavacamten, and the original mavacamten group received 128 weeks of mavacamten. All patients had comprehensive echocardiographic assessments (including LV and left atrial [LA] global longitudinal strain measurements using vendor neutral software [TOMTEC-ARENA TTA2, Philips Healthcare]) at baseline and 128-week follow-up.
Results
At week 128, there was a sustained improvement (mean percentage of change from baseline, all P < 0.05) in LVOT gradients (resting [–61%], post-Valsalva [–72%], and postexercise [–53%]), LV mass index (–11%), septal E/e′ (–18%), LV global longitudinal strain (4.5%), LA volume index (–6%), and LA strain (conduit strain [16%], contraction [35%], and reservoir [32%]). In 71 patients with ≥5 point improvement in the Kansas City Cardiomyopathy Questionnaire 23-item Clinical Summary Score (KCCQ-23-CSS), there was a significant and sustained improvement (all P < 0.05), whereas in 25 patients with <5 point improvement in the KCCQ-23-CSS, there was no significant improvement in various LA and LV strain values.
Conclusions
In the VALOR-HCM trial, treatment with mavacamten resulted in sustained favorable cardiac remodeling, including improvement in LVOT gradients, cardiac volumes, cardiac hypertrophy, diastolic function, and markers of LA and LV strain from baseline through week 128, suggesting disease modification. These favorable changes also occurred in association with meaningful improvement in quality of life.
{"title":"Long-Term Favorable Cardiac Remodeling in Obstructive Hypertrophic Cardiomyopathy Patients Treated With Mavacamten for Up to 128 Weeks","authors":"Milind Y. Desai MD, MBA , Yuichiro Okushi MD , Kathy Wolski MPH , Jeffrey B. Geske MD , Anjali Tiku Owens MD , Qiuqing Wang MPH , Sara Saberi MS, MD , Andrew Wang MD , Paul Cremer MS, MD , Neal K. Lakdawala MD , Mark V. Sherrid MD , Albree Tower-Rader MD , David R. Fermin MD , Mark A. Zenker MD , Srihari S. Naidu MD , Kathy Lampl MD , Steven E. Nissen MD , Zoran Popovic MD, MPH","doi":"10.1016/j.jcmg.2025.07.019","DOIUrl":"10.1016/j.jcmg.2025.07.019","url":null,"abstract":"<div><h3>Background</h3><div>In the VALOR-HCM (A Study to Evaluate Mavacamten in Adults With Symptomatic Obstructive HCM Who Are Eligible for Septal Reduction Therapy; <span><span>NCT04349072</span><svg><path></path></svg></span>) trial, patients with severely symptomatic obstructive hypertrophic cardiomyopathy (HCM) treated with mavacamten demonstrated significant improvement in left ventricular outflow tract (LVOT) gradients and echocardiographic indices of cardiac remodeling in the short term.</div></div><div><h3>Objectives</h3><div>The authors sought to assess whether mavacamten results in sustained favorable long-term cardiac remodeling at 128 weeks (end of trial).</div></div><div><h3>Methods</h3><div>A total of 112 adult symptomatic obstructive HCM patients (mean age: 60.3 years; 50% men; and 94% NYHA functional class III/IV) who were referred for septal reduction therapy were randomized 1:1 to mavacamten or placebo for 16 weeks. Subsequently, placebo patients transitioned to and received 112 weeks of mavacamten, and the original mavacamten group received 128 weeks of mavacamten. All patients had comprehensive echocardiographic assessments (including LV and left atrial [LA] global longitudinal strain measurements using vendor neutral software [TOMTEC-ARENA TTA2, Philips Healthcare]) at baseline and 128-week follow-up.</div></div><div><h3>Results</h3><div>At week 128, there was a sustained improvement (mean percentage of change from baseline, all <em>P</em> < 0.05) in LVOT gradients (resting [–61%], post-Valsalva [–72%], and postexercise [–53%]), LV mass index (–11%), septal E/e′ (–18%), LV global longitudinal strain (4.5%), LA volume index (–6%), and LA strain (conduit strain [16%], contraction [35%], and reservoir [32%]). In 71 patients with ≥5 point improvement in the Kansas City Cardiomyopathy Questionnaire 23-item Clinical Summary Score (KCCQ-23-CSS), there was a significant and sustained improvement (all <em>P</em> < 0.05), whereas in 25 patients with <5 point improvement in the KCCQ-23-CSS, there was no significant improvement in various LA and LV strain values.</div></div><div><h3>Conclusions</h3><div>In the VALOR-HCM trial, treatment with mavacamten resulted in sustained favorable cardiac remodeling, including improvement in LVOT gradients, cardiac volumes, cardiac hypertrophy, diastolic function, and markers of LA and LV strain from baseline through week 128, suggesting disease modification. These favorable changes also occurred in association with meaningful improvement in quality of life.</div></div>","PeriodicalId":14767,"journal":{"name":"JACC. Cardiovascular imaging","volume":"18 12","pages":"Pages 1300-1311"},"PeriodicalIF":15.2,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145069498","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-01DOI: 10.1016/j.jcmg.2025.10.019
Thierry G Donati,Francesca Ortelli,Monika Hebeisen,Alexandros Protonotarios,Paul A S Olsen,Ardan M Saguner,Firat Duru,Konstantinos Savvatis,Perry M Elliott,Kristina H Haugaa,Felix C Tanner
BACKGROUNDRight ventricular outflow tract (RVOT) dilatation is a phenotypic feature of arrhythmogenic right ventricular cardiomyopathy (ARVC). The echocardiographic RVOT diameter is part of the 2010 Task Force Criteria and is widely measured in clinical practice. Nevertheless, few data exist on its prevalence, diagnostic value, and prognostic significance.OBJECTIVESThis study aimed to explore the association of RVOT diameter with adverse outcomes in ARVC patients without (primary prevention) or with (secondary prevention) previous ventricular arrhythmia (VA), identify the best RVOT diameter for diagnosing ARVC, and understand whether isolated RVOT dilatation occurs in ARVC.METHODSPatients with definite ARVC and genetic testing results were included in a cross-sectional outcome study. Isolated RVOT dilatation was defined as an enlarged RVOT diameter without concurrent right ventricular (RV) end-diastolic area dilatation. The diagnostic power of RVOT diameter was assessed compared with 100 healthy control subjects. The time to first event after baseline echocardiography was analyzed by Cox regression.RESULTSThe cohort consisted of 370 patients (mean age: 47 years; 56% male; 65% primary prevention; median follow-up: 6.8 years [Q1-Q3: 3.8-10.5 years]; 136 events [100 VA; 35 deaths]). RVOT dilatation occurred in 69% and isolated dilatation in 24% of patients. All RVOT diameters had similar diagnostic power (RVOT3/body surface area, AUC: 0.71 [95% CI: 0.66-0.76]) and a similar association with VA (RVOT3/body surface area, HR: 1.08 [95% CI: 1.04-1.13]; P < 0.001) or death (HR: 1.26 [95% CI: 1.18-1.35]; P < 0.001). Dilated RVOT was associated with a shorter time to VA or death in primary prevention and death in secondary prevention, and its feasibility was higher, its reproducibility was better, and its outcome association was stronger than those of RV free-wall strain.CONCLUSIONSIsolated RVOT dilatation occurred in more than 20% of ARVC patients. All RVOT diameters showed good diagnostic power, were strongly associated with time to adverse events, were associated with adverse events in primary and secondary prevention, and exhibited superior feasibility, reproducibility, and outcome association compared with RV free-wall strain.
{"title":"Right Ventricular Outflow Tract Diameter for Event Prediction in Arrhythmogenic Right Ventricular Cardiomyopathy: Incremental Value Over Echocardiographic Free-Wall Strain.","authors":"Thierry G Donati,Francesca Ortelli,Monika Hebeisen,Alexandros Protonotarios,Paul A S Olsen,Ardan M Saguner,Firat Duru,Konstantinos Savvatis,Perry M Elliott,Kristina H Haugaa,Felix C Tanner","doi":"10.1016/j.jcmg.2025.10.019","DOIUrl":"https://doi.org/10.1016/j.jcmg.2025.10.019","url":null,"abstract":"BACKGROUNDRight ventricular outflow tract (RVOT) dilatation is a phenotypic feature of arrhythmogenic right ventricular cardiomyopathy (ARVC). The echocardiographic RVOT diameter is part of the 2010 Task Force Criteria and is widely measured in clinical practice. Nevertheless, few data exist on its prevalence, diagnostic value, and prognostic significance.OBJECTIVESThis study aimed to explore the association of RVOT diameter with adverse outcomes in ARVC patients without (primary prevention) or with (secondary prevention) previous ventricular arrhythmia (VA), identify the best RVOT diameter for diagnosing ARVC, and understand whether isolated RVOT dilatation occurs in ARVC.METHODSPatients with definite ARVC and genetic testing results were included in a cross-sectional outcome study. Isolated RVOT dilatation was defined as an enlarged RVOT diameter without concurrent right ventricular (RV) end-diastolic area dilatation. The diagnostic power of RVOT diameter was assessed compared with 100 healthy control subjects. The time to first event after baseline echocardiography was analyzed by Cox regression.RESULTSThe cohort consisted of 370 patients (mean age: 47 years; 56% male; 65% primary prevention; median follow-up: 6.8 years [Q1-Q3: 3.8-10.5 years]; 136 events [100 VA; 35 deaths]). RVOT dilatation occurred in 69% and isolated dilatation in 24% of patients. All RVOT diameters had similar diagnostic power (RVOT3/body surface area, AUC: 0.71 [95% CI: 0.66-0.76]) and a similar association with VA (RVOT3/body surface area, HR: 1.08 [95% CI: 1.04-1.13]; P < 0.001) or death (HR: 1.26 [95% CI: 1.18-1.35]; P < 0.001). Dilated RVOT was associated with a shorter time to VA or death in primary prevention and death in secondary prevention, and its feasibility was higher, its reproducibility was better, and its outcome association was stronger than those of RV free-wall strain.CONCLUSIONSIsolated RVOT dilatation occurred in more than 20% of ARVC patients. All RVOT diameters showed good diagnostic power, were strongly associated with time to adverse events, were associated with adverse events in primary and secondary prevention, and exhibited superior feasibility, reproducibility, and outcome association compared with RV free-wall strain.","PeriodicalId":14767,"journal":{"name":"JACC. Cardiovascular imaging","volume":"19 1","pages":""},"PeriodicalIF":14.0,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145663997","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-11-27DOI: 10.1016/j.jcmg.2025.10.023
Elliott S Moss,Edward G Jones,Shaine A Morris,Tam T Doan
{"title":"Mitral Annular Disjunction in Pediatric Loeys-Dietz Syndrome: A Step Toward Deep Phenotyping.","authors":"Elliott S Moss,Edward G Jones,Shaine A Morris,Tam T Doan","doi":"10.1016/j.jcmg.2025.10.023","DOIUrl":"https://doi.org/10.1016/j.jcmg.2025.10.023","url":null,"abstract":"","PeriodicalId":14767,"journal":{"name":"JACC. Cardiovascular imaging","volume":"140 1","pages":""},"PeriodicalIF":14.0,"publicationDate":"2025-11-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145644902","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-11-26DOI: 10.1016/j.jcmg.2025.10.024
Dermot M Phelan,Guido Claessen,Thijs M H Eijsvogels,Timothy W Churchill,Elizabeth H Dineen,Sabiha Gati,J Sawalla Guseh,Jeffrey J Hsu,Ankit B Shah,Brett W Sperry,Meagan M Wasfy,Andre La Gerche,Matthew W Martinez,Michael Papadakis,Aaron L Baggish,Jonathan H Kim,
Masters athletes (MAs), defined as individuals ≥35 years of age who are engaged in competitive or high-volume recreational sports or exercise training, comprise a growing group regularly cared for in sports cardiology. The cardiovascular care of MAs can be challenging because many of the classical tenets in sports cardiology and exercise physiology were derived from young, competitive athletes and therefore do not fully generalize to the care of MAs. Appropriate implementation of multimodality cardiovascular imaging is essential to guide the risk stratification and clinical management of MAs. In this state-of-the-art review, physiological and pathologic considerations unique to MAs are highlighted. The strengths and limitations of specific cardiovascular imaging modalities are reviewed along with guidance on their appropriate use in the care of MAs. The purpose of this document is to represent the first primary reference on best practice considerations for the use of multimodality cardiovascular imaging in the care of MAs.
{"title":"Cardiovascular Imaging Considerations for Masters-Aged Athletes.","authors":"Dermot M Phelan,Guido Claessen,Thijs M H Eijsvogels,Timothy W Churchill,Elizabeth H Dineen,Sabiha Gati,J Sawalla Guseh,Jeffrey J Hsu,Ankit B Shah,Brett W Sperry,Meagan M Wasfy,Andre La Gerche,Matthew W Martinez,Michael Papadakis,Aaron L Baggish,Jonathan H Kim, ","doi":"10.1016/j.jcmg.2025.10.024","DOIUrl":"https://doi.org/10.1016/j.jcmg.2025.10.024","url":null,"abstract":"Masters athletes (MAs), defined as individuals ≥35 years of age who are engaged in competitive or high-volume recreational sports or exercise training, comprise a growing group regularly cared for in sports cardiology. The cardiovascular care of MAs can be challenging because many of the classical tenets in sports cardiology and exercise physiology were derived from young, competitive athletes and therefore do not fully generalize to the care of MAs. Appropriate implementation of multimodality cardiovascular imaging is essential to guide the risk stratification and clinical management of MAs. In this state-of-the-art review, physiological and pathologic considerations unique to MAs are highlighted. The strengths and limitations of specific cardiovascular imaging modalities are reviewed along with guidance on their appropriate use in the care of MAs. The purpose of this document is to represent the first primary reference on best practice considerations for the use of multimodality cardiovascular imaging in the care of MAs.","PeriodicalId":14767,"journal":{"name":"JACC. Cardiovascular imaging","volume":"72 1","pages":""},"PeriodicalIF":14.0,"publicationDate":"2025-11-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145644936","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-11-24DOI: 10.1016/j.jcmg.2025.10.012
Borek Foldyna,Ibrahim Hadzic,Thomas Mayrhofer,Júlia Karády,Jana Taron,Márton Kolossváry,Vineet K Raghu,Sara McCallum,Kayla Paradis,Marissa R Diggs,Sarah M Chu,Alex B Lu,Charurut Somboonwit,Jose I Bernardino,Michael P Dubé,Craig A Sponseller,Markella V Zanni,Gerald S Bloomfield,Carlos D Malvestutto,Carl J Fichtenbaum,Judith A Aberg,Judith S Currier,Heather J Ribaudo,Pamela S Douglas,Michael T Lu,Steven K Grinspoon
BACKGROUNDThe effects of statin therapy on pericoronary adipose tissue (PCAT) and its relationship with plaque progression and outcomes in people with HIV (PWH) remain poorly understood.OBJECTIVESThe aim of this study was to evaluate PCAT density changes over time; statin effects on PCAT; and associations among PCAT changes, coronary plaque, and clinical outcomes.METHODSIn the REPRIEVE (Randomized Trial to Prevent Vascular Events in HIV) mechanistic computed tomographic (CT) substudy (n = 753, mean age 51 ± 6 years, 17% women), PCAT density was measured from noncontrast CT images at baseline and 2 years, while coronary plaque volumes (total, calcified, and noncalcified) were assessed from contrast-enhanced CT angiograms. Analyses were stratified by coronary artery disease burden (segment involvement score 0, 1-3, or ≥4) and adjusted for technical parameters, atherosclerotic cardiovascular disease risk, body mass index, inflammatory biomarkers, and statin allocation. Associations among PCAT, plaque changes, and events (all-cause mortality, major adverse cardiovascular events [MACE], and MACE or death) were evaluated.RESULTSBaseline PCAT density was -87.7 ± 10.5 HU, increasing by 4.5 HU (95% CI: 3.8-5.2; P < 0.001) over 2 years. Pitavastatin prevented this increase in participants with segment involvement scores ≥4 (-1.7 HU vs +3.8 HU; P = 0.016, pitavastatin vs placebo, respectively). Greater PCAT density was associated with higher noncalcified plaque volume (per +10 HU, +5.0 mm3; P = 0.075) and reduced calcified plaque progression (-3.2 mm3; P = 0.031). Over a median of 6.3 years, 4.2% of patients died. Baseline PCAT density was independently associated with all-cause mortality (HR per +10 HU: 1.95; 95% CI: 1.03-3.69; P = 0.040), but not MACE.CONCLUSIONSPCAT density increases over time in PWH, but pitavastatin mitigates this in those with high coronary artery disease burden. PCAT density is associated with vulnerable plaque morphology and all-cause mortality, supporting its potential as a prognostic imaging biomarker in PWH. (Randomized Trial to Prevent Vascular Events in HIV [REPRIEVE]; NCT02344290).
背景：他汀类药物治疗对HIV （PWH）患者冠状动脉周围脂肪组织（PCAT）的影响及其与斑块进展和结局的关系仍知之甚少。目的：本研究的目的是评估PCAT密度随时间的变化；他汀类药物对PCAT的影响；以及PCAT变化、冠状动脉斑块和临床结果之间的关系。方法在REPRIEVE（预防HIV血管事件的随机试验）机制计算机断层扫描（CT）亚研究（n = 753，平均年龄51±6岁，17%为女性）中，通过基线和2年的非对比CT图像测量PCAT密度，同时通过增强CT血管造影评估冠状动脉斑块体积（总、钙化和非钙化）。根据冠状动脉疾病负担（节段累及评分0、1-3或≥4）对分析进行分层，并根据技术参数、动脉粥样硬化性心血管疾病风险、体重指数、炎症生物标志物和他汀类药物分配进行调整。评估PCAT、斑块变化和事件（全因死亡率、主要不良心血管事件[MACE]以及MACE或死亡）之间的关系。结果基线PCAT密度为-87.7±10.5 HU， 2年内增加4.5 HU （95% CI: 3.8 ~ 5.2; P < 0.001）。匹伐他汀阻止了节段累及评分≥4的参与者的这种增加（-1.7 HU vs +3.8 HU; P = 0.016，匹伐他汀vs安慰剂）。更大的PCAT密度与更高的非钙化斑块体积（每+10 HU， +5.0 mm3, P = 0.075）和更少的钙化斑块进展（-3.2 mm3, P = 0.031）相关。在中位6.3年期间，4.2%的患者死亡。基线PCAT密度与全因死亡率独立相关（HR / +10 HU: 1.95; 95% CI: 1.03-3.69; P = 0.040），但与MACE无关。结论：PWH患者的spcat密度随时间增加，但匹伐他汀可减轻高冠状动脉疾病负担患者的spcat密度。PCAT密度与易损斑块形态和全因死亡率相关，支持其作为PWH预后成像生物标志物的潜力。预防HIV血管事件的随机试验[REPRIEVE]； NCT02344290)。
{"title":"Statin Effects on Pericoronary Adipose Tissue Density in People With HIV: Insights From the REPRIEVE Trial.","authors":"Borek Foldyna,Ibrahim Hadzic,Thomas Mayrhofer,Júlia Karády,Jana Taron,Márton Kolossváry,Vineet K Raghu,Sara McCallum,Kayla Paradis,Marissa R Diggs,Sarah M Chu,Alex B Lu,Charurut Somboonwit,Jose I Bernardino,Michael P Dubé,Craig A Sponseller,Markella V Zanni,Gerald S Bloomfield,Carlos D Malvestutto,Carl J Fichtenbaum,Judith A Aberg,Judith S Currier,Heather J Ribaudo,Pamela S Douglas,Michael T Lu,Steven K Grinspoon","doi":"10.1016/j.jcmg.2025.10.012","DOIUrl":"https://doi.org/10.1016/j.jcmg.2025.10.012","url":null,"abstract":"BACKGROUNDThe effects of statin therapy on pericoronary adipose tissue (PCAT) and its relationship with plaque progression and outcomes in people with HIV (PWH) remain poorly understood.OBJECTIVESThe aim of this study was to evaluate PCAT density changes over time; statin effects on PCAT; and associations among PCAT changes, coronary plaque, and clinical outcomes.METHODSIn the REPRIEVE (Randomized Trial to Prevent Vascular Events in HIV) mechanistic computed tomographic (CT) substudy (n = 753, mean age 51 ± 6 years, 17% women), PCAT density was measured from noncontrast CT images at baseline and 2 years, while coronary plaque volumes (total, calcified, and noncalcified) were assessed from contrast-enhanced CT angiograms. Analyses were stratified by coronary artery disease burden (segment involvement score 0, 1-3, or ≥4) and adjusted for technical parameters, atherosclerotic cardiovascular disease risk, body mass index, inflammatory biomarkers, and statin allocation. Associations among PCAT, plaque changes, and events (all-cause mortality, major adverse cardiovascular events [MACE], and MACE or death) were evaluated.RESULTSBaseline PCAT density was -87.7 ± 10.5 HU, increasing by 4.5 HU (95% CI: 3.8-5.2; P < 0.001) over 2 years. Pitavastatin prevented this increase in participants with segment involvement scores ≥4 (-1.7 HU vs +3.8 HU; P = 0.016, pitavastatin vs placebo, respectively). Greater PCAT density was associated with higher noncalcified plaque volume (per +10 HU, +5.0 mm3; P = 0.075) and reduced calcified plaque progression (-3.2 mm3; P = 0.031). Over a median of 6.3 years, 4.2% of patients died. Baseline PCAT density was independently associated with all-cause mortality (HR per +10 HU: 1.95; 95% CI: 1.03-3.69; P = 0.040), but not MACE.CONCLUSIONSPCAT density increases over time in PWH, but pitavastatin mitigates this in those with high coronary artery disease burden. PCAT density is associated with vulnerable plaque morphology and all-cause mortality, supporting its potential as a prognostic imaging biomarker in PWH. (Randomized Trial to Prevent Vascular Events in HIV [REPRIEVE]; NCT02344290).","PeriodicalId":14767,"journal":{"name":"JACC. Cardiovascular imaging","volume":"110 1","pages":""},"PeriodicalIF":14.0,"publicationDate":"2025-11-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145645015","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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