Pub Date : 2026-02-01Epub Date: 2025-09-22DOI: 10.1016/j.ahj.2025.09.010
Rose Crowley Bmed, MD , Sonia Azzopardi RN , Annie Curtin RN , Georgia Rendell RN , Louise Segan MBBS , Jeremy William MBBS , Kenneth Cho MBBS , Nicholas D’Elia MBBS , Margareta Sutija PhD , Tommy Kende MBBS, PhD , David Chieng MBBS, PhD , Hariharan Sugumar MBBS, PhD , Aleksandr Voskoboinik MBBS, PhD , Sandeep Prabhu MBBS, PhD , Liang-Han Ling MBBS, PhD , Vaughan G Macefield BSc, PhD, DSc , Jonathan M Kalman MBBS, PhD , Peter M Kistler MBBS, PhD
Background
Lifestyle modification is a key pillar of atrial fibrillation (AF) management. Yoga has beneficial effects on cardiovascular health and has shown promise as an intervention in AF. However, randomized data are absent.
Objectives
To determine the effect of regular yoga on AF episodes and AF burden in people with paroxysmal or persistent AF over a 12-month period.
Methods
This is a randomized control trial of a yoga program in addition to standard care, compared to standard care alone in people with paroxysmal or persistent AF undergoing a rhythm control management strategy. 222 participants will be randomized 1:1 to the yoga intervention or control. Yoga will be conducted in studio and online with a target of at least 3 classes/week. Controls will be instructed to exercise for at least 150 minutes/week. Rhythm monitoring will be with implantable loop recorder, or ECG capable smartwatch with AF detection and twice daily ECGs. Autonomic metrics will be assessed in the laboratory by HRV, blood pressure variability and direct recordings of muscle sympathetic nerve activity. Following a 3-month training period, the dual primary endpoints of AF recurrence (time to recurrence, as defined by any sustained atrial tachyarrhythmia lasting >1 hour) and AF burden will be determined at 12 months.
Conclusions
This study aims to determine the impact of yoga on AF recurrence and burden in people with paroxysmal and persistent AF. Yoga may provide an effective noninvasive, nonpharmacologic lifestyle strategy in the management of AF.
Trial Registration
The trial was preregistered with the Australian New Zealand Clinical Trials Registry (ACTRN12624000264583).
{"title":"Yoga vs regular exercise for atrial fibrillation: Design of the yoga-AF randomized controlled trial","authors":"Rose Crowley Bmed, MD , Sonia Azzopardi RN , Annie Curtin RN , Georgia Rendell RN , Louise Segan MBBS , Jeremy William MBBS , Kenneth Cho MBBS , Nicholas D’Elia MBBS , Margareta Sutija PhD , Tommy Kende MBBS, PhD , David Chieng MBBS, PhD , Hariharan Sugumar MBBS, PhD , Aleksandr Voskoboinik MBBS, PhD , Sandeep Prabhu MBBS, PhD , Liang-Han Ling MBBS, PhD , Vaughan G Macefield BSc, PhD, DSc , Jonathan M Kalman MBBS, PhD , Peter M Kistler MBBS, PhD","doi":"10.1016/j.ahj.2025.09.010","DOIUrl":"10.1016/j.ahj.2025.09.010","url":null,"abstract":"<div><h3>Background</h3><div>Lifestyle modification is a key pillar of atrial fibrillation (AF) management. Yoga has beneficial effects on cardiovascular health and has shown promise as an intervention in AF. However, randomized data are absent.</div></div><div><h3>Objectives</h3><div>To determine the effect of regular yoga on AF episodes and AF burden in people with paroxysmal or persistent AF over a 12-month period.</div></div><div><h3>Methods</h3><div>This is a randomized control trial of a yoga program in addition to standard care, compared to standard care alone in people with paroxysmal or persistent AF undergoing a rhythm control management strategy. 222 participants will be randomized 1:1 to the yoga intervention or control. Yoga will be conducted in studio and online with a target of at least 3 classes/week. Controls will be instructed to exercise for at least 150 minutes/week. Rhythm monitoring will be with implantable loop recorder, or ECG capable smartwatch with AF detection and twice daily ECGs. Autonomic metrics will be assessed in the laboratory by HRV, blood pressure variability and direct recordings of muscle sympathetic nerve activity. Following a 3-month training period, the dual primary endpoints of AF recurrence (time to recurrence, as defined by any sustained atrial tachyarrhythmia lasting >1 hour) and AF burden will be determined at 12 months.</div></div><div><h3>Conclusions</h3><div>This study aims to determine the impact of yoga on AF recurrence and burden in people with paroxysmal and persistent AF. Yoga may provide an effective noninvasive, nonpharmacologic lifestyle strategy in the management of AF.</div></div><div><h3>Trial Registration</h3><div>The trial was preregistered with the Australian New Zealand Clinical Trials Registry (ACTRN12624000264583).</div></div>","PeriodicalId":7868,"journal":{"name":"American heart journal","volume":"292 ","pages":"Article 107278"},"PeriodicalIF":3.5,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145136249","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-02-01Epub Date: 2025-10-17DOI: 10.1016/j.ahj.2025.107290
Linda Ye MD , Michael P. Girouard MD, MBA , Alan S. Go MD , Jane Y. Liu MPH , Rishi V. Parikh MPH , Thida C. Tan MPH , Emily S. Lee MD , Grace Sun BA , Rami Halaseh MD , Ankeet S. Bhatt MD, MBA, ScM , Leonid Pravoverov MD , Sijie Zheng MD , Jana Svetlichnaya MD , Jesse K. Fitzpatrick MD , Harshith R. Avula MD, MPH , Keane K. Lee MD, MS , Sirtaz Adatya MD , David Ouyang MD , Parag Goyal MD, MSc , Alexander T. Sandhu MD, MS , Andrew P. Ambrosy MD, MPH
Background
Chronic kidney disease (CKD) is a major risk factor for heart failure (HF). However, the burden of worsening HF (WHF) events among adults with mild-to-moderate CKD has not been well described.
Objectives
This study assessed the burden of WHF in a contemporary cohort of adults with mild-to-moderate CKD.
Methods
We identified adults with mild-to-moderate CKD (eGFR 30-59 mL/min/1.73m² or eGFR ≥60 mL/min/1.73m² with albuminuria) within a large, integrated healthcare delivery system from 2012 to 2021. Outcomes included hospitalizations, emergency department visits, and outpatient encounters for WHF, stratified by HF status and level of CKD.
Results
Among 375,495 adults with mild-to-moderate CKD, mean age was 64 ± 16 years, 54% were women, mean eGFR was 76 ± 26 mL/min/1.73m², and 6.5% had prior known HF. CKD stages G1A2 (31.6%), G2A2 (24.9%), and G3aA1 (25.1%) were most prevalent. Rates (95% CI) per 100 person-years for WHF events were 1.85 (1.83-1.87) for hospitalizations, 0.85 (0.84-0.86) for emergency department visits, and 0.83 (0.81-0.84) for outpatient encounters, resulting in a cumulative rate of 2.42 (2.40-2.44). Event rates were higher at lower eGFR and higher albuminuria levels.
Conclusions
WHF is a common source of morbidity in adults with earlier stage CKD, and particularly high in those with lower eGFR and greater albuminuria. These findings underscore the importance of implementing available and emerging cardioprotective and renoprotective therapies in this high-risk population.
{"title":"Worsening heart failure events in adults with mild-to-moderate chronic kidney disease","authors":"Linda Ye MD , Michael P. Girouard MD, MBA , Alan S. Go MD , Jane Y. Liu MPH , Rishi V. Parikh MPH , Thida C. Tan MPH , Emily S. Lee MD , Grace Sun BA , Rami Halaseh MD , Ankeet S. Bhatt MD, MBA, ScM , Leonid Pravoverov MD , Sijie Zheng MD , Jana Svetlichnaya MD , Jesse K. Fitzpatrick MD , Harshith R. Avula MD, MPH , Keane K. Lee MD, MS , Sirtaz Adatya MD , David Ouyang MD , Parag Goyal MD, MSc , Alexander T. Sandhu MD, MS , Andrew P. Ambrosy MD, MPH","doi":"10.1016/j.ahj.2025.107290","DOIUrl":"10.1016/j.ahj.2025.107290","url":null,"abstract":"<div><h3>Background</h3><div>Chronic kidney disease (CKD) is a major risk factor for heart failure (HF). However, the burden of worsening HF (WHF) events among adults with mild-to-moderate CKD has not been well described.</div></div><div><h3>Objectives</h3><div>This study assessed the burden of WHF in a contemporary cohort of adults with mild-to-moderate CKD.</div></div><div><h3>Methods</h3><div>We identified adults with mild-to-moderate CKD (eGFR 30-59 mL/min/1.73m² or eGFR ≥60 mL/min/1.73m² with albuminuria) within a large, integrated healthcare delivery system from 2012 to 2021. Outcomes included hospitalizations, emergency department visits, and outpatient encounters for WHF, stratified by HF status and level of CKD.</div></div><div><h3>Results</h3><div>Among 375,495 adults with mild-to-moderate CKD, mean age was 64 ± 16 years, 54% were women, mean eGFR was 76 ± 26 mL/min/1.73m², and 6.5% had prior known HF. CKD stages G1A2 (31.6%), G2A2 (24.9%), and G3aA1 (25.1%) were most prevalent. Rates (95% CI) per 100 person-years for WHF events were 1.85 (1.83-1.87) for hospitalizations, 0.85 (0.84-0.86) for emergency department visits, and 0.83 (0.81-0.84) for outpatient encounters, resulting in a cumulative rate of 2.42 (2.40-2.44). Event rates were higher at lower eGFR and higher albuminuria levels.</div></div><div><h3>Conclusions</h3><div>WHF is a common source of morbidity in adults with earlier stage CKD, and particularly high in those with lower eGFR and greater albuminuria. These findings underscore the importance of implementing available and emerging cardioprotective and renoprotective therapies in this high-risk population.</div></div>","PeriodicalId":7868,"journal":{"name":"American heart journal","volume":"292 ","pages":"Article 107290"},"PeriodicalIF":3.5,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145328176","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-02-01Epub Date: 2025-09-12DOI: 10.1016/j.ahj.2025.09.004
Joseph B Lerman MD , Dwight D. Koeberl MD, PhD , Shilpi Epstein MD , Lothar Roessig MD , Rodica Stan PhD , Meghan Halley PhD , Anjali T. Owens MD , Barry Greenberg MD , Kevin M. Alexander MD , Sharlene M. Day MD , Mathew S. Maurer MD , Eric D. Adler MD , Adrian F. Hernandez MD , Euan A Ashley MD, PhD , G. Michael Felker MD
Rare cardiovascular diseases, while individually uncommon, collectively affect millions of people worldwide and are associated with significant morbidity, mortality, and economic burden. Despite this considerable impact, most rare cardiovascular diseases lack approved treatments. Developing therapies for rare cardiovascular diseases requires overcoming a unique set of challenges. This includes barriers to accurate patient diagnosis (and therefore to trial cohort generation), small cohort sizes, the choice of effective clinical trial endpoints, unique ethical and regulatory concerns, and the often-substantial costs of such therapies (which may limit public access to treatment). Despite such challenges, the past decade has witnessed a significant increase in the successful development of rare cardiovascular disease therapies. This review provides an overview of the challenges, while also highlighting potential strategies to advance the field.
{"title":"Developing therapeutics for rare cardiovascular diseases","authors":"Joseph B Lerman MD , Dwight D. Koeberl MD, PhD , Shilpi Epstein MD , Lothar Roessig MD , Rodica Stan PhD , Meghan Halley PhD , Anjali T. Owens MD , Barry Greenberg MD , Kevin M. Alexander MD , Sharlene M. Day MD , Mathew S. Maurer MD , Eric D. Adler MD , Adrian F. Hernandez MD , Euan A Ashley MD, PhD , G. Michael Felker MD","doi":"10.1016/j.ahj.2025.09.004","DOIUrl":"10.1016/j.ahj.2025.09.004","url":null,"abstract":"<div><div>Rare cardiovascular diseases, while individually uncommon, collectively affect millions of people worldwide and are associated with significant morbidity, mortality, and economic burden. Despite this considerable impact, most rare cardiovascular diseases lack approved treatments. Developing therapies for rare cardiovascular diseases requires overcoming a unique set of challenges<strong>.</strong> This includes barriers to accurate patient diagnosis (and therefore to trial cohort generation), small cohort sizes, the choice of effective clinical trial endpoints, unique ethical and regulatory concerns, and the often-substantial costs of such therapies (which may limit public access to treatment). Despite such challenges, the past decade has witnessed a significant increase in the successful development of rare cardiovascular disease therapies. This review provides an overview of the challenges, while also highlighting potential strategies to advance the field.</div></div>","PeriodicalId":7868,"journal":{"name":"American heart journal","volume":"292 ","pages":"Article 107272"},"PeriodicalIF":3.5,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145063085","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-02-01Epub Date: 2025-10-09DOI: 10.1016/j.ahj.2025.107287
Olivia Girolamo BMedSc , Muhammad Dzafir Ismail MBBS, MMed , Rosanna Tavella BSc, PhD , Eng Lee Ooi MBBS, PhD , Sivabaskari Pasupathy BSc, PhD , Sarena La BMedSc , Abdul Sheikh MBBS, MD , Christopher Zeitz MBBS, PhD , John Beltrame BSc, BMBS, PhD
Background
The Coronary Slow Flow Phenomenon (CSFP) is considered a coronary microvascular disorder and has been defined as a corrected thrombolysis in myocardial infarction frame count (cTFC) ≥25 frames. Recent invasive physiology studies have reported that cTFC is not a surrogate marker for coronary microvascular dysfunction (CMD), defined by an abnormal Coronary Flow Reserve (CFR), questioning the integrity of CSFP. This study evaluates the Functional Coronary Angiography (FCA) findings of patients with and without CSFP, as well as the relationship between cTFC and invasive coronary functional measures.
Methods
FCA utilizing a pressure-Doppler flow wire during adenosine infusion, and acetylcholine provocation, was undertaken in 103 patients with angina and non-obstructive coronary artery disease (<50% stenosis; ANOCA).
Results
The FCA findings revealed CMD (i.e. CFR<2) in 43%, inducible coronary artery spasm (58%) and microvascular spasm (13%) in patients with the CSFP (n = 69), which was similar to those without CSFP (n = 34). However, the CSFP patients had a lower resting coronary blood flow velocity (19 ± 7 vs 23 ± 7cm/s, P = .009) with higher resting microvascular resistance (5.8 ± 1.9 vs 4.4 ± 1.7mmHg/cm/s, P = .006) and higher hyperemic microvascular resistance (2.35 ± 1.09 vs 1.94 ± 0.93, P = .049), despite a similar hyperemic CFR (2.25 ± 0.84 vs 2.26 ± 0.58, P = .971) compared to those without CSFP. Furthermore, the cTFC as a continuous measure, correlated with resting coronary blood flow, resting/hyperemic resistance but not CFR.
Conclusion
The conventional marker of CMD (i.e. CFR <2) was similar in patients with/without the CSFP. However alternative hemodynamic markers of impaired coronary microvascular function were abnormal in patients with the CSFP, including resting/hyperemic coronary microvascular resistance. Moreover, cTFC is a simple semi-quantitative marker correlated with coronary microvascular resistance and thus has clinical utility in the diagnosis of the CSFP.
{"title":"Functional coronary angiogram findings in angina with non-obstructive coronary arteries patients with coronary slow flow","authors":"Olivia Girolamo BMedSc , Muhammad Dzafir Ismail MBBS, MMed , Rosanna Tavella BSc, PhD , Eng Lee Ooi MBBS, PhD , Sivabaskari Pasupathy BSc, PhD , Sarena La BMedSc , Abdul Sheikh MBBS, MD , Christopher Zeitz MBBS, PhD , John Beltrame BSc, BMBS, PhD","doi":"10.1016/j.ahj.2025.107287","DOIUrl":"10.1016/j.ahj.2025.107287","url":null,"abstract":"<div><h3>Background</h3><div>The Coronary Slow Flow Phenomenon (CSFP) is considered a coronary microvascular disorder and has been defined as a corrected thrombolysis in myocardial infarction frame count (cTFC) ≥25 frames. Recent invasive physiology studies have reported that cTFC is not a surrogate marker for coronary microvascular dysfunction (CMD), defined by an abnormal Coronary Flow Reserve (CFR), questioning the integrity of CSFP. This study evaluates the Functional Coronary Angiography (FCA) findings of patients with and without CSFP, as well as the relationship between cTFC and invasive coronary functional measures.</div></div><div><h3>Methods</h3><div>FCA utilizing a pressure-Doppler flow wire during adenosine infusion, and acetylcholine provocation, was undertaken in 103 patients with angina and non-obstructive coronary artery disease (<50% stenosis; ANOCA).</div></div><div><h3>Results</h3><div>The FCA findings revealed CMD (i.e. CFR<2) in 43%, inducible coronary artery spasm (58%) and microvascular spasm (13%) in patients with the CSFP (<em>n</em> = 69), which was similar to those without CSFP (<em>n</em> = 34). However, the CSFP patients had a lower resting coronary blood flow velocity (19 ± 7 vs 23 ± 7cm/s, <em>P = .</em>009) with higher resting microvascular resistance (5.8 ± 1.9 vs 4.4 ± 1.7mmHg/cm/s, <em>P = .</em>006) and higher hyperemic microvascular resistance (2.35 ± 1.09 vs 1.94 ± 0.93, <em>P = .</em>049), despite a similar hyperemic CFR (2.25 ± 0.84 vs 2.26 ± 0.58, <em>P = .</em>971) compared to those without CSFP. Furthermore, the cTFC as a continuous measure, correlated with resting coronary blood flow, resting/hyperemic resistance but not CFR.</div></div><div><h3>Conclusion</h3><div>The conventional marker of CMD (i.e. CFR <2) was similar in patients with/without the CSFP. However alternative hemodynamic markers of impaired coronary microvascular function were abnormal in patients with the CSFP, including resting/hyperemic coronary microvascular resistance. Moreover, cTFC is a simple semi-quantitative marker correlated with coronary microvascular resistance and thus has clinical utility in the diagnosis of the CSFP.</div></div>","PeriodicalId":7868,"journal":{"name":"American heart journal","volume":"292 ","pages":"Article 107287"},"PeriodicalIF":3.5,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145257129","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-02-01Epub Date: 2025-11-01DOI: 10.1016/j.ahj.2025.107293
Kimberley I. Hemelrijk MD , Victor A. Jimenez-Diaz MD PhD , Jean Paul Vilchez MD , Juan F Oteo MD , Ivan Gomez-Blazquez MD , Manel Sabate MD, PhD , Victoria Vilalta MD PhD , Alberto Berenguer Jofresa MD FESC , Lluis Asmarats MD, PhD , Ignacio J Amat-Santos MD PhD , Antonio Tello-Montoliu MD , Jose M. de la Torre Hernandez MD, PhD , Xacobe Flores MD , Livia Gheorghe MD , Vicente Peral MD , Antonio J Muñoz-Garcia MD , Fernando Alfonso MD , Gabriela Tirado-Conte MD , Salvatore Brugaletta MD PhD , Gabriela Veiga MD, PhD , Luis Nombela-Franco MD PhD
Background
Patients undergoing transcatheter aortic valve implantation (TAVI) frequently experience life-threatening ischemic and bleeding complications. However, management of antithrombotic therapy after TAVI in patients without oral anticoagulation (OAC), particularly in patients with high burden for subsequent ischemic events, has limited evidence from randomized controlled trials.
Methods
The REAC TAVI2 trial is a prospective, multicenter, open-label, phase III randomized trial (NCT05283356). A total of 1206 patients undergoing TAVI with high ischemic risk (defined as concomitant coronary artery disease, diabetes mellitus or peripheral vascular disease) will be randomized in a 1:1 ratio to single antiplatelet therapy with aspirin (100 mg once daily) or low-dose ticagrelor (60 mg twice daily). The primary endpoint is the incidence of a net adverse clinical event (NACE) at 1-year after TAVI. NACE is defined as a composite of all-cause mortality, cerebrovascular events, myocardial infarction, progressive angina leading to emergency evaluation, rehospitalization or new coronary angiogram, clinical valve thrombosis, acute limb ischemia leading to hospitalization, and type 2, 3, or 5 bleeding. The secondary endpoint is the incidence of subclinical valve thrombosis detected by hypo-attenuated leaflet thickening and reduced leaflet motion at 3 and 12 months post-TAVI assessed by 4-dimensional computed tomography.
Summary
In patients undergoing TAVI without an indication for OAC, there is a need for antiplatelet therapy that provides protection against ischemic events without increasing bleeding, particularly in the subset of patients at heightened risk of ischemic events. The REAC-TAVI 2 is a randomized multicenter clinical trial designed to study the effect of single antiplatelet therapy with aspirin compared to low-dose ticagrelor on a composite outcome of all-cause mortality, ischemic, and bleeding events after TAVI.
{"title":"Rationale and design of REAC-TAVI 2: Single antiplatelet treatment with ticagrelor vs aspirin after transcatheter aortic valve implantation","authors":"Kimberley I. Hemelrijk MD , Victor A. Jimenez-Diaz MD PhD , Jean Paul Vilchez MD , Juan F Oteo MD , Ivan Gomez-Blazquez MD , Manel Sabate MD, PhD , Victoria Vilalta MD PhD , Alberto Berenguer Jofresa MD FESC , Lluis Asmarats MD, PhD , Ignacio J Amat-Santos MD PhD , Antonio Tello-Montoliu MD , Jose M. de la Torre Hernandez MD, PhD , Xacobe Flores MD , Livia Gheorghe MD , Vicente Peral MD , Antonio J Muñoz-Garcia MD , Fernando Alfonso MD , Gabriela Tirado-Conte MD , Salvatore Brugaletta MD PhD , Gabriela Veiga MD, PhD , Luis Nombela-Franco MD PhD","doi":"10.1016/j.ahj.2025.107293","DOIUrl":"10.1016/j.ahj.2025.107293","url":null,"abstract":"<div><h3>Background</h3><div>Patients undergoing transcatheter aortic valve implantation (TAVI) frequently experience life-threatening ischemic and bleeding complications. However, management of antithrombotic therapy after TAVI in patients without oral anticoagulation (OAC), particularly in patients with high burden for subsequent ischemic events, has limited evidence from randomized controlled trials.</div></div><div><h3>Methods</h3><div>The REAC TAVI2 trial is a prospective, multicenter, open-label, phase III randomized trial (NCT05283356). A total of 1206 patients undergoing TAVI with high ischemic risk (defined as concomitant coronary artery disease, diabetes mellitus or peripheral vascular disease) will be randomized in a 1:1 ratio to single antiplatelet therapy with aspirin (100 mg once daily) or low-dose ticagrelor (60 mg twice daily). The primary endpoint is the incidence of a net adverse clinical event (NACE) at 1-year after TAVI. NACE is defined as a composite of all-cause mortality, cerebrovascular events, myocardial infarction, progressive angina leading to emergency evaluation, rehospitalization or new coronary angiogram, clinical valve thrombosis, acute limb ischemia leading to hospitalization, and type 2, 3, or 5 bleeding. The secondary endpoint is the incidence of subclinical valve thrombosis detected by hypo-attenuated leaflet thickening and reduced leaflet motion at 3 and 12 months post-TAVI assessed by 4-dimensional computed tomography.</div></div><div><h3>Summary</h3><div>In patients undergoing TAVI without an indication for OAC, there is a need for antiplatelet therapy that provides protection against ischemic events without increasing bleeding, particularly in the subset of patients at heightened risk of ischemic events. The REAC-TAVI 2 is a randomized multicenter clinical trial designed to study the effect of single antiplatelet therapy with aspirin compared to low-dose ticagrelor on a composite outcome of all-cause mortality, ischemic, and bleeding events after TAVI.</div></div>","PeriodicalId":7868,"journal":{"name":"American heart journal","volume":"292 ","pages":"Article 107293"},"PeriodicalIF":3.5,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145429941","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Real-world characteristics and outcomes in patients with heart failure (HF) and reduced ejection fraction (HFrEF) treated with vericiguat remain unclear. We investigated patient characteristics, hypotension—the most relevant clinical event—, and outcomes after initiating vericiguat in patients with HFrEF.
Methods
In this nationwide, multicentre retrospective study involving 22 hospitals in Japan, we examined symptomatic or asymptomatic hypotension and drug discontinuation within 90 days after initiation of vericiguat in patients with left ventricular ejection fraction <45%. The association between hypotension and HF outcomes was also examined.
Results
Among the 799 patients with HFrEF, the mean age was 69.6 years, and 218 (27.3%) were female. Of them, 316 (39.5%) had New York Heart Association classification III or IV, and 329 (41.8%) had systolic blood pressure (sBP) <100 mm Hg. Hypotension was observed in 25.3% of patients within 90 days, with asymptomatic hypotension being the most common (17.9%). By contrast, drug discontinuation related to hypotension was less frequent (4.4%). After adjustment, sBP <100 mm Hg, low body mass index, and in-hospital vericiguat initiation were associated with the incidence of hypotension within 90 days. Patients who experienced hypotension had a greater risk of cardiovascular death or HF hospitalization than those who did not (P = .01).
Conclusions
Although hypotension was relatively common soon after starting vericiguat, they were not often associated with drug discontinuation. Patients experiencing hypotension had a greater risk of HF outcomes, but this would be primarily associated with their vulnerability, given the infrequent discontinuation.
{"title":"Vericiguat and hypotension in patients with heart failure and reduced ejection fraction: VERIFY-HF registry","authors":"Shingo Matsumoto MD, PhD , Takahito Nasu MD, PhD , Wataru Fujimoto MD, PhD , Nobuyuki Kagiyama MD, PhD , Yasuyuki Shiraishi MD, PhD , Shunsuke Ishii MD, PhD , Takeshi Ijichi MD, PhD , Gaku Nakazawa MD, PhD , Takanori Ikeda MD, PhD , Koshiro Kanaoka MD, PhD","doi":"10.1016/j.ahj.2025.09.013","DOIUrl":"10.1016/j.ahj.2025.09.013","url":null,"abstract":"<div><h3>Background</h3><div>Real-world characteristics and outcomes in patients with heart failure (HF) and reduced ejection fraction (HFrEF) treated with vericiguat remain unclear. We investigated patient characteristics, hypotension—the most relevant clinical event—, and outcomes after initiating vericiguat in patients with HFrEF.</div></div><div><h3>Methods</h3><div>In this nationwide, multicentre retrospective study involving 22 hospitals in Japan, we examined symptomatic or asymptomatic hypotension and drug discontinuation within 90 days after initiation of vericiguat in patients with left ventricular ejection fraction <45%. The association between hypotension and HF outcomes was also examined.</div></div><div><h3>Results</h3><div>Among the 799 patients with HFrEF, the mean age was 69.6 years, and 218 (27.3%) were female. Of them, 316 (39.5%) had New York Heart Association classification III or IV, and 329 (41.8%) had systolic blood pressure (sBP) <100 mm Hg. Hypotension was observed in 25.3% of patients within 90 days, with asymptomatic hypotension being the most common (17.9%). By contrast, drug discontinuation related to hypotension was less frequent (4.4%). After adjustment, sBP <100 mm Hg, low body mass index, and in-hospital vericiguat initiation were associated with the incidence of hypotension within 90 days. Patients who experienced hypotension had a greater risk of cardiovascular death or HF hospitalization than those who did not (<em>P</em> = .01).</div></div><div><h3>Conclusions</h3><div>Although hypotension was relatively common soon after starting vericiguat, they were not often associated with drug discontinuation. Patients experiencing hypotension had a greater risk of HF outcomes, but this would be primarily associated with their vulnerability, given the infrequent discontinuation.</div></div>","PeriodicalId":7868,"journal":{"name":"American heart journal","volume":"292 ","pages":"Article 107281"},"PeriodicalIF":3.5,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145136233","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-02-01Epub Date: 2025-09-30DOI: 10.1016/j.ahj.2025.107283
Joseph Rossano MD , Charles Canter MD , Cordula Wolf MD , Nicholas Favatella PharmD , Jeffrey Lockman PhD , Shilpa Puli PhD , Atefeh Javidialsaadi PhD , Joshua Dyme MD , Christina Crevar MS , Seema Mital MD
Background
Mavacamten, a first-in-class cardiac myosin inhibitor, is approved internationally for the treatment of symptomatic adult patients with obstructive hypertrophic cardiomyopathy (HCM) and has been shown to improve cardiac function and symptoms in adult patients across multiple phase 3 trials. The efficacy and safety of mavacamten in pediatric patients with obstructive HCM has not been evaluated.
Methods
SCOUT-HCM is a phase 3, randomized, placebo-controlled, double-blind, parallel-group, multicenter, international study in symptomatic adolescent patients (12 years to <18 years old) with obstructive HCM. The aim of the study is to assess the efficacy, safety, and pharmacokinetics of mavacamten in this population. Participants will be randomized 1:1 to mavacamten or placebo for 28 weeks, followed by a 28-week active-treatment period (when patients randomized to placebo will cross over to mavacamten) and an open-label long-term extension period for ≤144 weeks. Participants will initiate mavacamten at a dosage of 2.5 mg/day or 5 mg/day; dose titration will be based on echocardiographic assessment of Valsalva left ventricular (LV) outflow tract (LVOT) gradient and LV ejection fraction. The primary endpoint is change from baseline to week 28 in Valsalva LVOT gradient. Secondary endpoints include efficacy parameters of resting and post-exercise LVOT gradients, peak oxygen consumption, symptoms, and health status, plus safety and pharmacokinetic parameters.
Conclusions
SCOUT-HCM is the first clinical trial to evaluate a cardiac myosin inhibitor in adolescent patients with obstructive HCM. SCOUT-HCM will assess the utility of mavacamten in this patient population with an unmet clinical need.
{"title":"Mavacamten in symptomatic adolescent patients with obstructive hypertrophic cardiomyopathy: design of the phase 3 SCOUT-HCM trial","authors":"Joseph Rossano MD , Charles Canter MD , Cordula Wolf MD , Nicholas Favatella PharmD , Jeffrey Lockman PhD , Shilpa Puli PhD , Atefeh Javidialsaadi PhD , Joshua Dyme MD , Christina Crevar MS , Seema Mital MD","doi":"10.1016/j.ahj.2025.107283","DOIUrl":"10.1016/j.ahj.2025.107283","url":null,"abstract":"<div><h3>Background</h3><div>Mavacamten, a first-in-class cardiac myosin inhibitor, is approved internationally for the treatment of symptomatic adult patients with obstructive hypertrophic cardiomyopathy (HCM) and has been shown to improve cardiac function and symptoms in adult patients across multiple phase 3 trials. The efficacy and safety of mavacamten in pediatric patients with obstructive HCM has not been evaluated.</div></div><div><h3>Methods</h3><div>SCOUT-HCM is a phase 3, randomized, placebo-controlled, double-blind, parallel-group, multicenter, international study in symptomatic adolescent patients (12 years to <18 years old) with obstructive HCM. The aim of the study is to assess the efficacy, safety, and pharmacokinetics of mavacamten in this population. Participants will be randomized 1:1 to mavacamten or placebo for 28 weeks, followed by a 28-week active-treatment period (when patients randomized to placebo will cross over to mavacamten) and an open-label long-term extension period for ≤144 weeks. Participants will initiate mavacamten at a dosage of 2.5 mg/day or 5 mg/day; dose titration will be based on echocardiographic assessment of Valsalva left ventricular (LV) outflow tract (LVOT) gradient and LV ejection fraction. The primary endpoint is change from baseline to week 28 in Valsalva LVOT gradient. Secondary endpoints include efficacy parameters of resting and post-exercise LVOT gradients, peak oxygen consumption, symptoms, and health status, plus safety and pharmacokinetic parameters.</div></div><div><h3>Conclusions</h3><div>SCOUT-HCM is the first clinical trial to evaluate a cardiac myosin inhibitor in adolescent patients with obstructive HCM. SCOUT-HCM will assess the utility of mavacamten in this patient population with an unmet clinical need.</div></div><div><h3>Trial registration</h3><div>ClinicalTrials.gov: NCT06253221</div></div>","PeriodicalId":7868,"journal":{"name":"American heart journal","volume":"292 ","pages":"Article 107283"},"PeriodicalIF":3.5,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145211409","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-02-01Epub Date: 2025-10-03DOI: 10.1016/j.ahj.2025.107285
Tayyab Shah MD , Samantha Coratti BA , David Farraday BA , Laurie Norton MA, MBE , Charles Rareshide MS , Jingsan Zhu MS, MBA , Michael G. Levin MD , Sae-Hwan Park PhD , Scott M. Damrauer MD , Jay S. Giri MD, MHS , Neel P. Chokshi MD, MBA , Benjamin M. Jackson MD, MS , Mitesh S. Patel MD, MBA , Alexander C. Fanaroff MD, MHS
Directly contacting eligible participants with an offer to join a randomized clinical trial (RCT) is an efficient recruitment method, but the effect of different outreach strategies on enrollment fraction and completion of the trial protocol is uncertain. In a study within a trial (SWAT) of an RCT testing a physical activity intervention in patients with peripheral artery disease, eligible patients were randomized to receive an email with an invitation to join the study and a link to the trial’s online platform (“opt-in”) or to receive an email framing participation as part of the standard of care followed by telephone outreach from a study coordinator (“opt-out”). Among 5176 participants contacted by unsolicited email (3909 opt-in, 1267 opt-out), enrollment fraction was 1.0% in the opt-in arm (n = 39) versus 3.6% in the opt-out arm (n = 45) (OR 3.65, 95% CI 2.37-5.64); there were no significant differences between opt-in and opt-out participants in the rate of completion of trial protocol steps. This SWAT of recruitment strategies demonstrates the potential for opt-out framing and active outreach to increase enrollment fraction without compromising protocol completion in direct-to-participant RCTs.
{"title":"Effect of opt-in versus opt-out framing on trial recruitment: a study within a trial of the GAMEPAD randomized trial","authors":"Tayyab Shah MD , Samantha Coratti BA , David Farraday BA , Laurie Norton MA, MBE , Charles Rareshide MS , Jingsan Zhu MS, MBA , Michael G. Levin MD , Sae-Hwan Park PhD , Scott M. Damrauer MD , Jay S. Giri MD, MHS , Neel P. Chokshi MD, MBA , Benjamin M. Jackson MD, MS , Mitesh S. Patel MD, MBA , Alexander C. Fanaroff MD, MHS","doi":"10.1016/j.ahj.2025.107285","DOIUrl":"10.1016/j.ahj.2025.107285","url":null,"abstract":"<div><div>Directly contacting eligible participants with an offer to join a randomized clinical trial (RCT) is an efficient recruitment method, but the effect of different outreach strategies on enrollment fraction and completion of the trial protocol is uncertain. In a study within a trial (SWAT) of an RCT testing a physical activity intervention in patients with peripheral artery disease, eligible patients were randomized to receive an email with an invitation to join the study and a link to the trial’s online platform (“opt-in”) or to receive an email framing participation as part of the standard of care followed by telephone outreach from a study coordinator (“opt-out”). Among 5176 participants contacted by unsolicited email (3909 opt-in, 1267 opt-out), enrollment fraction was 1.0% in the opt-in arm (<em>n</em> = 39) versus 3.6% in the opt-out arm (<em>n</em> = 45) (OR 3.65, 95% CI 2.37-5.64); there were no significant differences between opt-in and opt-out participants in the rate of completion of trial protocol steps. This SWAT of recruitment strategies demonstrates the potential for opt-out framing and active outreach to increase enrollment fraction without compromising protocol completion in direct-to-participant RCTs.</div></div>","PeriodicalId":7868,"journal":{"name":"American heart journal","volume":"292 ","pages":"Article 107285"},"PeriodicalIF":3.5,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145231441","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-02-01Epub Date: 2025-10-19DOI: 10.1016/j.ahj.2025.107292
William J. He MD MHS , Brenton R. Prescott MS , Vanessa Xanthakis PhD , Gary F. Mitchell MD , Susan Cheng MD , Ramachandran S. Vasan MD
Background
Previous studies have reported that obesity-related metabolic abnormalities (eg, diabetes and hypertension) lead to myocardial dysfunction and adverse cardiac remodeling. However, it is unclear whether such cardiac remodeling is from obesity or obesity-related metabolic abnormalities. We hypothesize that overweight and obesity are associated with adverse cardiac remodeling independent of associated metabolic abnormalities.
Methods
We evaluated 6,639 participants from the Framingham Heart Study who underwent echocardiography and had no prevalent cardiovascular disease. Individuals were classified into 6 obesity sub-phenotypes based on metabolic health (metabolically healthy or metabolically unhealthy) and body mass index (normal weight, overweight, or obese). Obesity subphenotypes were related to echocardiographic measures using multivariable regression analyses.
Results
Mean age was 49 years and 55% were women. Overweight and obesity were consistently associated with adverse cardiac remodeling in both metabolic healthy and unhealthy participants. Among metabolically healthy participants, compared to the normal weight group (referent), overweight and obesity were significantly associated with increased left ventricular mass (11.6 and 21.4 gm), left atrium end-systolic dimension (0.27 and 0.48 cm), global longitudinal strain (0.82 and 1.06%), and the ratio of early diastolic trans-mitral flow velocity to early diastolic mitral annulus velocity (0.35 and 0.87) (all P < .001). Additionally, obesity was significantly associated with mitral annular plane systolic excursion (0.08 cm, P < .001) and relative wall thickness (0.01, P = .001) compared to the normal weight referent group.
Conclusions
Increasing body weight was associated with adverse cardiac remodeling regardless of metabolic health status, which suggests that obesity may directly increase the risk of adverse cardiac remodeling.
{"title":"Association of obesity subphenotypes with indices of cardiac remodeling in the Framingham heart study","authors":"William J. He MD MHS , Brenton R. Prescott MS , Vanessa Xanthakis PhD , Gary F. Mitchell MD , Susan Cheng MD , Ramachandran S. Vasan MD","doi":"10.1016/j.ahj.2025.107292","DOIUrl":"10.1016/j.ahj.2025.107292","url":null,"abstract":"<div><h3>Background</h3><div>Previous studies have reported that obesity-related metabolic abnormalities (eg, diabetes and hypertension) lead to myocardial dysfunction and adverse cardiac remodeling. However, it is unclear whether such cardiac remodeling is from obesity or obesity-related metabolic abnormalities. We hypothesize that overweight and obesity are associated with adverse cardiac remodeling independent of associated metabolic abnormalities.</div></div><div><h3>Methods</h3><div>We evaluated 6,639 participants from the Framingham Heart Study who underwent echocardiography and had no prevalent cardiovascular disease. Individuals were classified into 6 obesity sub-phenotypes based on metabolic health (metabolically healthy or metabolically unhealthy) and body mass index (normal weight, overweight, or obese). Obesity subphenotypes were related to echocardiographic measures using multivariable regression analyses.</div></div><div><h3>Results</h3><div>Mean age was 49 years and 55% were women. Overweight and obesity were consistently associated with adverse cardiac remodeling in both metabolic healthy and unhealthy participants. Among metabolically healthy participants, compared to the normal weight group (referent), overweight and obesity were significantly associated with increased left ventricular mass (11.6 and 21.4 gm), left atrium end-systolic dimension (0.27 and 0.48 cm), global longitudinal strain (0.82 and 1.06%), and the ratio of early diastolic trans-mitral flow velocity to early diastolic mitral annulus velocity (0.35 and 0.87) (all <em>P</em> < .001). Additionally, obesity was significantly associated with mitral annular plane systolic excursion (0.08 cm, <em>P</em> < .001) and relative wall thickness (0.01, <em>P</em> = .001) compared to the normal weight referent group.</div></div><div><h3>Conclusions</h3><div>Increasing body weight was associated with adverse cardiac remodeling regardless of metabolic health status, which suggests that obesity may directly increase the risk of adverse cardiac remodeling.</div></div>","PeriodicalId":7868,"journal":{"name":"American heart journal","volume":"292 ","pages":"Article 107292"},"PeriodicalIF":3.5,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145342938","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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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