Pub Date : 2024-09-04DOI: 10.1016/j.ahj.2024.08.023
Masaki Kodaira, Mohammad Sazzad Hasan, Yoni Grossman, Carlos Guerrero, Liming Guo, Aihua Liu, Judith Therrien, Ariane Marelli
Background: Cardiovascular complications due to viral infection pose a significant risk in vulnerable patients such as those with congenital heart disease (CHD). Limited data exists regarding the incidence of influenza and its impact on cardiovascular outcomes among this specific patient population.
Methods: A retrospective cohort study was designed using the Canadian Congenital Heart Disease (CanCHD) database - a pan-Canadian database of CHD patients with up to 35 years of follow-up. CHD patients aged 40 to 65 years with influenza virus-associated hospitalizations between 2010 and 2017 were identified and 1:1 matched with CHD patients with limb fracture hospitalizations on age and calendar time. Our primary endpoint was cardiovascular complications: heart failure, acute myocardial infarction, atrial arrhythmia, ventricular arrhythmia, heart block, myocarditis, and pericarditis.
Results: Of the 303 patients identified with incident influenza virus-associated hospitalizations, 255 were matched to 255 patients with limb fracture hospitalizations. Patients with influenza virus-related hospitalizations showed significantly higher cumulative probability of cardiovascular complications at one year (0.16 vs. 0.03) and five years (0.33 vs. 0.15) compared to patients hospitalized with bone fracture. Time-dependent hazard function modeling demonstrated a significantly higher risk of cardiovascular complications within nine months post-discharge for influenza-related hospitalizations. This association was confirmed by Cox regression model (average hazard ratio throughout follow-up: 2.48; 95% CI: 1.59 - 3.84).
Conclusions: This pan-Canadian cohort study of adults with CHD demonstrated an association between influenza virus-related hospitalization and risk of cardiovascular complications during the nine months post discharge. This data is essential in planning surveillance strategies to mitigate adverse outcomes and provides insights into interpreting complication rates of other emerging pathogens, such as COVID-19.
{"title":"Risk of Cardiovascular Events after Influenza Infection-related Hospitalizations in Adults with Congenital Heart Disease -A Nationwide Population Based Study.","authors":"Masaki Kodaira, Mohammad Sazzad Hasan, Yoni Grossman, Carlos Guerrero, Liming Guo, Aihua Liu, Judith Therrien, Ariane Marelli","doi":"10.1016/j.ahj.2024.08.023","DOIUrl":"https://doi.org/10.1016/j.ahj.2024.08.023","url":null,"abstract":"<p><strong>Background: </strong>Cardiovascular complications due to viral infection pose a significant risk in vulnerable patients such as those with congenital heart disease (CHD). Limited data exists regarding the incidence of influenza and its impact on cardiovascular outcomes among this specific patient population.</p><p><strong>Methods: </strong>A retrospective cohort study was designed using the Canadian Congenital Heart Disease (CanCHD) database - a pan-Canadian database of CHD patients with up to 35 years of follow-up. CHD patients aged 40 to 65 years with influenza virus-associated hospitalizations between 2010 and 2017 were identified and 1:1 matched with CHD patients with limb fracture hospitalizations on age and calendar time. Our primary endpoint was cardiovascular complications: heart failure, acute myocardial infarction, atrial arrhythmia, ventricular arrhythmia, heart block, myocarditis, and pericarditis.</p><p><strong>Results: </strong>Of the 303 patients identified with incident influenza virus-associated hospitalizations, 255 were matched to 255 patients with limb fracture hospitalizations. Patients with influenza virus-related hospitalizations showed significantly higher cumulative probability of cardiovascular complications at one year (0.16 vs. 0.03) and five years (0.33 vs. 0.15) compared to patients hospitalized with bone fracture. Time-dependent hazard function modeling demonstrated a significantly higher risk of cardiovascular complications within nine months post-discharge for influenza-related hospitalizations. This association was confirmed by Cox regression model (average hazard ratio throughout follow-up: 2.48; 95% CI: 1.59 - 3.84).</p><p><strong>Conclusions: </strong>This pan-Canadian cohort study of adults with CHD demonstrated an association between influenza virus-related hospitalization and risk of cardiovascular complications during the nine months post discharge. This data is essential in planning surveillance strategies to mitigate adverse outcomes and provides insights into interpreting complication rates of other emerging pathogens, such as COVID-19.</p>","PeriodicalId":7868,"journal":{"name":"American heart journal","volume":null,"pages":null},"PeriodicalIF":3.7,"publicationDate":"2024-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142144983","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 : 2024-09-04DOI: 10.1016/j.ahj.2024.07.004
{"title":"Response to Tomoyuki Kawada: Blood and urine metal levels in patients with diabetes and cardiovascular disease","authors":"","doi":"10.1016/j.ahj.2024.07.004","DOIUrl":"10.1016/j.ahj.2024.07.004","url":null,"abstract":"","PeriodicalId":7868,"journal":{"name":"American heart journal","volume":null,"pages":null},"PeriodicalIF":3.7,"publicationDate":"2024-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142136321","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 : 2024-09-04DOI: 10.1016/j.ahj.2024.07.003
{"title":"Blood and urine metal levels in patients with diabetes and cardiovascular disease","authors":"","doi":"10.1016/j.ahj.2024.07.003","DOIUrl":"10.1016/j.ahj.2024.07.003","url":null,"abstract":"","PeriodicalId":7868,"journal":{"name":"American heart journal","volume":null,"pages":null},"PeriodicalIF":3.7,"publicationDate":"2024-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142136320","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 : 2024-09-03DOI: 10.1016/j.ahj.2024.08.014
Sheldon E Litwin, Jan Komtebedde, Barry A Borlaug, David M Kaye, Gerd Hasenfuβ, Rami Kawash, Elke Hoendermis, Scott L Hummel, Maja Cikes, Finn Gustafsson, Eugene Chung, Rajeev Mohan, Aaron L Sverdlov, Vijendra Swarup, Sebastian Winkler, Christopher S Hayward, Martin W Bergmann, Heiko Bugger, Scott McKenzie, Ajith Nair, Andreas Rieth, Daniel Burkhoff, Donald E Cutlip, Scott D Solomon, Dirk J van Veldhuisen, Martin B Leon, Sanjiv J Shah
Background: There is a little evidence regarding long-term safety and efficacy for atrial shunt devices in heart failure (HF).
Methods: The REDUCE LAP-HF I (n=44) and II (n=621) trials (RCT-I and -II) were multicenter, randomized, sham-controlled trials of patients with HF and ejection fraction >40%. Outcome data were analyzed from RCT-I, a mechanistic trial with 5-year follow-up, and RCT-II, a pivotal trial identifying a responder group (n=313) defined by exercise PVR <1.74 WU and no cardiac rhythm management device with 3-year follow-up.
Results: At 5 years in RCT I, there were no differences in cardiovascular (CV) mortality, HF events, embolic stroke, or new-onset atrial fibrillation between groups. After 3 years in RCT II, there was no difference in the primary outcome (hierarchical composite of CV mortality, stroke, HF events, and KCCQ) between shunt and sham in the overall trial. Compared to sham, those with responder characteristics in RCT-II had a better outcome with shunt (win ratio 1.6 [95% CI 1.2-2.2], P=0.006; 44% reduction in HF events [shunt 9 vs. control 16 per 100 patient-years], P=0.005; and greater improvement in KCCQ overall summary score [+17.9±20.0 vs. +7.6±20.4], P<0.001), while non-responders had significantly more HF events. Shunt treatment at 3 years was associated with a higher rate of ischemic stroke (3.2% vs. 0%, 95% CI 2% - 6.1%, p=0.032) and lower incidence of worsening kidney dysfunction (10.7% vs. 19.3%, p=0.041).
Conclusions: With up to 5 years of follow up, adverse events were low in patients receiving atrial shunts. In the responder group, atrial shunt treatment was associated with a significantly lower HF event rate and improved KCCQ compared to sham through 3 years of follow-up.
{"title":"Long term safety and outcomes after atrial shunting for heart failure with preserved or mildly reduced ejection fraction: 5-year and 3-year follow-up in the REDUCE LAP-HF I and II trials.","authors":"Sheldon E Litwin, Jan Komtebedde, Barry A Borlaug, David M Kaye, Gerd Hasenfuβ, Rami Kawash, Elke Hoendermis, Scott L Hummel, Maja Cikes, Finn Gustafsson, Eugene Chung, Rajeev Mohan, Aaron L Sverdlov, Vijendra Swarup, Sebastian Winkler, Christopher S Hayward, Martin W Bergmann, Heiko Bugger, Scott McKenzie, Ajith Nair, Andreas Rieth, Daniel Burkhoff, Donald E Cutlip, Scott D Solomon, Dirk J van Veldhuisen, Martin B Leon, Sanjiv J Shah","doi":"10.1016/j.ahj.2024.08.014","DOIUrl":"https://doi.org/10.1016/j.ahj.2024.08.014","url":null,"abstract":"<p><strong>Background: </strong>There is a little evidence regarding long-term safety and efficacy for atrial shunt devices in heart failure (HF).</p><p><strong>Methods: </strong>The REDUCE LAP-HF I (n=44) and II (n=621) trials (RCT-I and -II) were multicenter, randomized, sham-controlled trials of patients with HF and ejection fraction >40%. Outcome data were analyzed from RCT-I, a mechanistic trial with 5-year follow-up, and RCT-II, a pivotal trial identifying a responder group (n=313) defined by exercise PVR <1.74 WU and no cardiac rhythm management device with 3-year follow-up.</p><p><strong>Results: </strong>At 5 years in RCT I, there were no differences in cardiovascular (CV) mortality, HF events, embolic stroke, or new-onset atrial fibrillation between groups. After 3 years in RCT II, there was no difference in the primary outcome (hierarchical composite of CV mortality, stroke, HF events, and KCCQ) between shunt and sham in the overall trial. Compared to sham, those with responder characteristics in RCT-II had a better outcome with shunt (win ratio 1.6 [95% CI 1.2-2.2], P=0.006; 44% reduction in HF events [shunt 9 vs. control 16 per 100 patient-years], P=0.005; and greater improvement in KCCQ overall summary score [+17.9±20.0 vs. +7.6±20.4], P<0.001), while non-responders had significantly more HF events. Shunt treatment at 3 years was associated with a higher rate of ischemic stroke (3.2% vs. 0%, 95% CI 2% - 6.1%, p=0.032) and lower incidence of worsening kidney dysfunction (10.7% vs. 19.3%, p=0.041).</p><p><strong>Conclusions: </strong>With up to 5 years of follow up, adverse events were low in patients receiving atrial shunts. In the responder group, atrial shunt treatment was associated with a significantly lower HF event rate and improved KCCQ compared to sham through 3 years of follow-up.</p><p><strong>Clinicaltrials: </strong>gov registration: NCT02600234, NCT03088033.</p>","PeriodicalId":7868,"journal":{"name":"American heart journal","volume":null,"pages":null},"PeriodicalIF":3.7,"publicationDate":"2024-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142139056","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 : 2024-09-02DOI: 10.1016/j.ahj.2024.08.020
Eva Havers-Borgersen, Christian Jøns, Jawad H Butt, Michael Rahbek Schmidt, Klaus Juul, Mathis Gröning, Chee Woon Lim, Annette Schophuus Jensen, Morten Smerup, Lars Køber, Emil L Fosbøl
Background: As more patients with congenital heart disease (CHD) survive into adulthood, the population of adults with CHD is expanding. This trend is accompanied by an increasing incidence of complications, including arrhythmias. However, the long-term risk of arrhythmias remains sparsely investigated.
Methods: In this observational cohort study, all Danish patients with CHD born from 1977 to 2024 were identified using registries and followed from date of birth until the occurrence of arrhythmia, emigration, death, or end of follow-up (March 2024). The risk of arrhythmias was assessed among patients with CHD and compared to age- and sex-matched controls from the background population.
Results: A total of 45,820 patients with CHD (50.9% men) were identified and matched with 183,280 controls from the background population. During a median follow-up of 21.5 years, 2.6% of patients with CHD and 0.2% of controls developed arrhythmias - corresponding to incidence rates (IR) of 1.2 (95%CI 1.2-1.3) and 0.1 (95%CI 0.1-0.1) per 1,000 PY, respectively, and a hazard ratio (HR) of 16.4 (95%CI 14.4-18.7). The most common arrhythmias in patients with CHD were advanced atrioventricular block (IR 0.4 [95%CI 0.4-0.4] per 1,000 PY) and atrial flutter/fibrillation (IR 0.5 [95%CI 0.5-0.6] per 1,000 PY). Patients with malformations of the heart chambers, transposition of the great arteries, tetralogy of Fallot, and atrioventricular septal defect were at the highest risk of arrhythmias. Moreover, the risk of arrhythmias among those with ASD was not negligible. In patients with CHD, arrhythmia was associated with a significantly higher risk of death (HR of 6.9 [95%CI 5.9-8.1]).
Conclusions: Patients with CHD are at significantly higher risk of arrhythmias than the background population, and those with complex CHD are at particularly high risk. In patients with CHD, arrhythmia is associated with an increased risk of death. Additional studies are warranted to investigate how we can improve the diagnosis and management of arrhythmias in CHD.
{"title":"Arrhythmias in Congenital Heart Disease: a Nationwide Cohort Study.","authors":"Eva Havers-Borgersen, Christian Jøns, Jawad H Butt, Michael Rahbek Schmidt, Klaus Juul, Mathis Gröning, Chee Woon Lim, Annette Schophuus Jensen, Morten Smerup, Lars Køber, Emil L Fosbøl","doi":"10.1016/j.ahj.2024.08.020","DOIUrl":"https://doi.org/10.1016/j.ahj.2024.08.020","url":null,"abstract":"<p><strong>Background: </strong>As more patients with congenital heart disease (CHD) survive into adulthood, the population of adults with CHD is expanding. This trend is accompanied by an increasing incidence of complications, including arrhythmias. However, the long-term risk of arrhythmias remains sparsely investigated.</p><p><strong>Methods: </strong>In this observational cohort study, all Danish patients with CHD born from 1977 to 2024 were identified using registries and followed from date of birth until the occurrence of arrhythmia, emigration, death, or end of follow-up (March 2024). The risk of arrhythmias was assessed among patients with CHD and compared to age- and sex-matched controls from the background population.</p><p><strong>Results: </strong>A total of 45,820 patients with CHD (50.9% men) were identified and matched with 183,280 controls from the background population. During a median follow-up of 21.5 years, 2.6% of patients with CHD and 0.2% of controls developed arrhythmias - corresponding to incidence rates (IR) of 1.2 (95%CI 1.2-1.3) and 0.1 (95%CI 0.1-0.1) per 1,000 PY, respectively, and a hazard ratio (HR) of 16.4 (95%CI 14.4-18.7). The most common arrhythmias in patients with CHD were advanced atrioventricular block (IR 0.4 [95%CI 0.4-0.4] per 1,000 PY) and atrial flutter/fibrillation (IR 0.5 [95%CI 0.5-0.6] per 1,000 PY). Patients with malformations of the heart chambers, transposition of the great arteries, tetralogy of Fallot, and atrioventricular septal defect were at the highest risk of arrhythmias. Moreover, the risk of arrhythmias among those with ASD was not negligible. In patients with CHD, arrhythmia was associated with a significantly higher risk of death (HR of 6.9 [95%CI 5.9-8.1]).</p><p><strong>Conclusions: </strong>Patients with CHD are at significantly higher risk of arrhythmias than the background population, and those with complex CHD are at particularly high risk. In patients with CHD, arrhythmia is associated with an increased risk of death. Additional studies are warranted to investigate how we can improve the diagnosis and management of arrhythmias in CHD.</p>","PeriodicalId":7868,"journal":{"name":"American heart journal","volume":null,"pages":null},"PeriodicalIF":3.7,"publicationDate":"2024-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142131661","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 : 2024-09-02DOI: 10.1016/j.ahj.2024.08.021
Michael D Nelson, Joanne M Gomez-Arnold, Janet Wei, Marie Lauzon, Sauyeh Zamani, Jenna Maughan, Okezi Obrutu, Chrisandra Shufelt, Eileen Handberg, Carl Pepine, C Noel Bairey Merz
Background: There are sex differences in left ventricular ejection fraction (LVEF) relevant to prognosis where women experience greater mortality at relatively higher LVEF compared to men, yet mechanistic understanding of this adverse prognosis is limited. Women with suspected ischemia with no obstructive coronary disease (INOCA) develop heart failure with preserved ejection fraction (HFpEF), yet contributors to LVEF remain largely unknown.
Methods: In 370 women with suspected ischemia with no obstructive coronary disease (INOCA) who prospectively underwent cardiac magnetic resonance imaging (CMRI), we investigated the contributions of LV morphology, function, and myocardial perfusion reserve on LVEF using univariate and multiple linear regression.
Results: A majority 71% of participants had high LVEF (>65%), followed by 24% having normal LVEF (55-65%), and only 5% having low EF (<55%). Baseline characteristics were comparable among the three groups, with the exception of age which was six years higher in the high LVEF group (p<0.01). Women in the high LVEF group also had the lowest LV cavity volume, greatest LV mass-volume ratio, and highest LV end-systolic elastance (all p < 0.05, adjusted for age, BMI, diabetes, and blood pressure). Myocardial perfusion reserve index was low in all groups (mean MPRI < 2.1) but was not significantly different across the spectrum of LVEF (p=0.458).
Conclusions: Taken together, these data demonstrate that the majority of women with suspected INOCA have elevated LVEF related to smaller, thicker ventricles with greater contractility. Future work is needed to better understand the specific mechanisms driving morphologic and functional changes in women with INOCA, and relations to longer-term HFpEF and mortality.
{"title":"Contributors to high left ventricular ejection fraction in women with ischemia and no obstructive coronary artery disease: Results from the Women's Ischemia Syndrome Evaluation - Coronary Vascular Dysfunction (WISE-CVD) Study.","authors":"Michael D Nelson, Joanne M Gomez-Arnold, Janet Wei, Marie Lauzon, Sauyeh Zamani, Jenna Maughan, Okezi Obrutu, Chrisandra Shufelt, Eileen Handberg, Carl Pepine, C Noel Bairey Merz","doi":"10.1016/j.ahj.2024.08.021","DOIUrl":"https://doi.org/10.1016/j.ahj.2024.08.021","url":null,"abstract":"<p><strong>Background: </strong>There are sex differences in left ventricular ejection fraction (LVEF) relevant to prognosis where women experience greater mortality at relatively higher LVEF compared to men, yet mechanistic understanding of this adverse prognosis is limited. Women with suspected ischemia with no obstructive coronary disease (INOCA) develop heart failure with preserved ejection fraction (HFpEF), yet contributors to LVEF remain largely unknown.</p><p><strong>Methods: </strong>In 370 women with suspected ischemia with no obstructive coronary disease (INOCA) who prospectively underwent cardiac magnetic resonance imaging (CMRI), we investigated the contributions of LV morphology, function, and myocardial perfusion reserve on LVEF using univariate and multiple linear regression.</p><p><strong>Results: </strong>A majority 71% of participants had high LVEF (>65%), followed by 24% having normal LVEF (55-65%), and only 5% having low EF (<55%). Baseline characteristics were comparable among the three groups, with the exception of age which was six years higher in the high LVEF group (p<0.01). Women in the high LVEF group also had the lowest LV cavity volume, greatest LV mass-volume ratio, and highest LV end-systolic elastance (all p < 0.05, adjusted for age, BMI, diabetes, and blood pressure). Myocardial perfusion reserve index was low in all groups (mean MPRI < 2.1) but was not significantly different across the spectrum of LVEF (p=0.458).</p><p><strong>Conclusions: </strong>Taken together, these data demonstrate that the majority of women with suspected INOCA have elevated LVEF related to smaller, thicker ventricles with greater contractility. Future work is needed to better understand the specific mechanisms driving morphologic and functional changes in women with INOCA, and relations to longer-term HFpEF and mortality.</p><p><strong>Clinical trials registration: </strong>NCT02582021.</p>","PeriodicalId":7868,"journal":{"name":"American heart journal","volume":null,"pages":null},"PeriodicalIF":3.7,"publicationDate":"2024-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142131662","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 : 2024-09-02DOI: 10.1016/j.ahj.2024.08.022
Emmanuel De Cock, Shakeel Kautbally, Frank Timmermans, Kris Bogaerts, Claude Hanet, Walter Desmet, Olivier Gurné, Pascal Vranckx, Nick Hiltrop, Karl Dujardin, Philippe Vanduynhoven, Paul Vermeersch, Charles Pirlet, Kurt Hermans, Bert Van Reet, Bert Ferdinande, Adel Aminian, Willem Dewilde, Antoine Guédès, François Simon, Frederic De Roeck, Frédéric De Vroey, J Wouter Jukema, Peter Sinnaeve, Ian Buysschaert
Patients with coronary artery disease (CAD) remain vulnerable to future major atherosclerotic events after revascularization, despite effective secondary prevention strategies. Inflammation plays a central role in the pathogenesis of CAD and recurrent events. To date, there is no specific anti-inflammatory medicine available with proven effective, cost-efficient, and favorable benefit-risk profile, except for colchicine. Initial studies with colchicine have sparked major interest in targeting atherosclerotic events with anti-inflammatory agents, but further studies are warranted to enforce the role of colchicine role as a major treatment pillar in CAD. Given colchicine's low cost and established acceptable long-term safety profile, confirming its efficacy through a pragmatic trial holds the potential to significantly impact the global burden of cardiovascular disease. The COL BE PCI trial is an investigator-initiated, multicenter, double-blind, event-driven trial. It will enroll 2,770 patients with chronic or acute CAD treated with percutaneous coronary intervention (PCI) at 19 sites in Belgium, applying lenient in- and exclusion criteria and including at least 30% female participants. Patients will be randomized between 2 hours and 5 days post-PCI to receive either colchicine 0.5 mg daily or placebo on top of contemporary optimal medical therapy and without run-in period. All patients will have baseline hsCRP measurements and a Second Manifestations of Arterial Disease (SMART) risk score calculation. The primary endpoint is the time from randomization to the first occurrence of a composite endpoint consisting of all-cause death, spontaneous non-fatal myocardial infarction, non-fatal stroke, or coronary revascularization. The trial is event-driven and will continue until 566 events have been reached, providing 80% power to detect a 21 % reduction in the primary endpoint taking a premature discontinuation of 15% into account. We expect a trial duration of approximately 44 months. The COL BE PCI Trial aims to assess the effectiveness and safety of administering low-dose colchicine for the secondary prevention in patients with both chronic and acute coronary artery disease undergoing PCI. Trial registration: ClinicalTrials.gov: NCT06095765.
{"title":"Low-dose colchicine for the prevention of cardiovascular events after percutaneous coronary intervention: rationale and design of the COL BE PCI trial: Short title: Rationale and design of the COL BE PCI trial.","authors":"Emmanuel De Cock, Shakeel Kautbally, Frank Timmermans, Kris Bogaerts, Claude Hanet, Walter Desmet, Olivier Gurné, Pascal Vranckx, Nick Hiltrop, Karl Dujardin, Philippe Vanduynhoven, Paul Vermeersch, Charles Pirlet, Kurt Hermans, Bert Van Reet, Bert Ferdinande, Adel Aminian, Willem Dewilde, Antoine Guédès, François Simon, Frederic De Roeck, Frédéric De Vroey, J Wouter Jukema, Peter Sinnaeve, Ian Buysschaert","doi":"10.1016/j.ahj.2024.08.022","DOIUrl":"https://doi.org/10.1016/j.ahj.2024.08.022","url":null,"abstract":"<p><p>Patients with coronary artery disease (CAD) remain vulnerable to future major atherosclerotic events after revascularization, despite effective secondary prevention strategies. Inflammation plays a central role in the pathogenesis of CAD and recurrent events. To date, there is no specific anti-inflammatory medicine available with proven effective, cost-efficient, and favorable benefit-risk profile, except for colchicine. Initial studies with colchicine have sparked major interest in targeting atherosclerotic events with anti-inflammatory agents, but further studies are warranted to enforce the role of colchicine role as a major treatment pillar in CAD. Given colchicine's low cost and established acceptable long-term safety profile, confirming its efficacy through a pragmatic trial holds the potential to significantly impact the global burden of cardiovascular disease. The COL BE PCI trial is an investigator-initiated, multicenter, double-blind, event-driven trial. It will enroll 2,770 patients with chronic or acute CAD treated with percutaneous coronary intervention (PCI) at 19 sites in Belgium, applying lenient in- and exclusion criteria and including at least 30% female participants. Patients will be randomized between 2 hours and 5 days post-PCI to receive either colchicine 0.5 mg daily or placebo on top of contemporary optimal medical therapy and without run-in period. All patients will have baseline hsCRP measurements and a Second Manifestations of Arterial Disease (SMART) risk score calculation. The primary endpoint is the time from randomization to the first occurrence of a composite endpoint consisting of all-cause death, spontaneous non-fatal myocardial infarction, non-fatal stroke, or coronary revascularization. The trial is event-driven and will continue until 566 events have been reached, providing 80% power to detect a 21 % reduction in the primary endpoint taking a premature discontinuation of 15% into account. We expect a trial duration of approximately 44 months. The COL BE PCI Trial aims to assess the effectiveness and safety of administering low-dose colchicine for the secondary prevention in patients with both chronic and acute coronary artery disease undergoing PCI. Trial registration: ClinicalTrials.gov: NCT06095765.</p>","PeriodicalId":7868,"journal":{"name":"American heart journal","volume":null,"pages":null},"PeriodicalIF":3.7,"publicationDate":"2024-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142131663","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 : 2024-08-30DOI: 10.1016/j.ahj.2024.08.017
Background
Accelerometer-measured physical activity is an increasingly used endpoint in heart failure (HF) trials. We investigated the determinants of accelerometer-measured physical activity and the relationship with patient-reported health status.
Methods
Post-hoc analysis of the Empire HF trial, including outpatients with HF with reduced ejection fraction (HFrEF). Physical activity was quantified as average accelerometer counts per minute (CPM) with higher values representing higher activity. We investigated associations between activity level and clinical variables, including age, sex, and body mass index, as well as patient-reported health status assessed by Kansas City Cardiomyopathy Questionnaire (KCCQ).
Results
Complete data were available in 180 (95%) patients (86% male, mean age 65 year). Baseline median physical activity level was 1,318 CPM (Q1-Q3 1,111-1,585). Age and anemia were independently associated with activity level (β-coefficients: −10 CPM per year age increase [95% CI −16 to −5.1], P = .00015, and −126 CPM for anemia [95% CI −9.1 to −244], P = .035). Significant independent associations were observed between activity level and all KCCQ summary scores (β-coefficient point estimates of 3.7, 4.6, and 4.9 CPM, all P < .02). For 12-week changes in KCCQ-summary scores, only the KCCQ-CSS was associated with activity level; mean increase of 17.5 CPM [95% CI 1.5 to 34.0], P = 0.032, per 5-point increase in KCCQ-CSS. Associations were not modified by treatment allocation (interaction P-values > .05).
Conclusions
In patients with HFrEF, older age and anemia were independently associated with lower activity. Moreover, physical activity only weakly increased with better health status, suggesting that changes in physical activity reflect improvements in patients’ health status to a limited degree. This highlights the need to better understand the endpoint with regards to all other health parameters to ease interpretation in future HF trials.
{"title":"Accelerometer-measured physical activity in patients with heart failure and reduced ejection fraction: Determinants and relationship with patient-reported health status","authors":"","doi":"10.1016/j.ahj.2024.08.017","DOIUrl":"10.1016/j.ahj.2024.08.017","url":null,"abstract":"<div><h3>Background</h3><p>Accelerometer-measured physical activity is an increasingly used endpoint in heart failure (HF) trials. We investigated the determinants of accelerometer-measured physical activity and the relationship with patient-reported health status.</p></div><div><h3>Methods</h3><p>Post-hoc analysis of the Empire HF trial, including outpatients with HF with reduced ejection fraction (HFrEF). Physical activity was quantified as average accelerometer counts per minute (CPM) with higher values representing higher activity. We investigated associations between activity level and clinical variables, including age, sex, and body mass index, as well as patient-reported health status assessed by Kansas City Cardiomyopathy Questionnaire (KCCQ).</p></div><div><h3>Results</h3><p>Complete data were available in 180 (95%) patients (86% male, mean age 65 year). Baseline median physical activity level was 1,318 CPM (Q1-Q3 1,111-1,585). Age and anemia were independently associated with activity level (β-coefficients: −10 CPM per year age increase [95% CI −16 to −5.1], <em>P</em> = .00015, and −126 CPM for anemia [95% CI −9.1 to −244], <em>P</em> = .035). Significant independent associations were observed between activity level and all KCCQ summary scores (β-coefficient point estimates of 3.7, 4.6, and 4.9 CPM, all <em>P</em> < .02). For 12-week changes in KCCQ-summary scores, only the KCCQ-CSS was associated with activity level; mean increase of 17.5 CPM [95% CI 1.5 to 34.0], <em>P</em> = 0.032, per 5-point increase in KCCQ-CSS. Associations were not modified by treatment allocation (interaction <em>P</em>-values > .05).</p></div><div><h3>Conclusions</h3><p>In patients with HFrEF, older age and anemia were independently associated with lower activity. Moreover, physical activity only weakly increased with better health status, suggesting that changes in physical activity reflect improvements in patients’ health status to a limited degree. This highlights the need to better understand the endpoint with regards to all other health parameters to ease interpretation in future HF trials.</p></div>","PeriodicalId":7868,"journal":{"name":"American heart journal","volume":null,"pages":null},"PeriodicalIF":3.7,"publicationDate":"2024-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0002870324002205/pdfft?md5=90ab1af541729a5f7e4c80e436878665&pid=1-s2.0-S0002870324002205-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142103690","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-08-29DOI: 10.1016/j.ahj.2024.08.011
Background
Direct oral anticoagulants are the standard of care for stroke prevention in eligible patients with atrial fibrillation and atrial flutter; however, bleeding remains a significant concern, limiting their use. Milvexian is an oral Factor XIa inhibitor that may offer similar anticoagulant efficacy with less bleeding risk.
Methods
LIBREXIA AF (NCT05757869) is a global phase III, randomized, double-blind, parallel-group, event-driven trial to compare milvexian with apixaban in participants with atrial fibrillation or atrial flutter. Participants are randomly assigned to milvexian 100 mg or apixaban (5 mg or 2.5 mg per label indication) twice daily. The primary efficacy objective is to evaluate if milvexian is noninferior to apixaban for the prevention of stroke and systemic embolism. The principal safety objective is to evaluate if milvexian is superior to apixaban in reducing the endpoint of International Society of Thrombosis and Hemostasis (ISTH) major bleeding events and the composite endpoint of ISTH major and clinically relevant nonmajor (CRNM) bleeding events. In total, 15,500 participants from approximately 1,000 sites in over 30 countries are planned to be enrolled. They will be followed until both 430 primary efficacy outcome events and 530 principal safety events are observed, which is estimated to take approximately 4 years.
Conclusion
The LIBREXIA AF study will determine the efficacy and safety of the oral Factor XIa inhibitor milvexian compared with apixaban in participants with either atrial fibrillation or atrial flutter.
{"title":"Milvexian vs apixaban for stroke prevention in atrial fibrillation: The LIBREXIA atrial fibrillation trial rationale and design","authors":"","doi":"10.1016/j.ahj.2024.08.011","DOIUrl":"10.1016/j.ahj.2024.08.011","url":null,"abstract":"<div><h3>Background</h3><p>Direct oral anticoagulants are the standard of care for stroke prevention in eligible patients with atrial fibrillation and atrial flutter; however, bleeding remains a significant concern, limiting their use. Milvexian is an oral Factor XIa inhibitor that may offer similar anticoagulant efficacy with less bleeding risk.</p></div><div><h3>Methods</h3><p>LIBREXIA AF (NCT05757869) is a global phase III, randomized, double-blind, parallel-group, event-driven trial to compare milvexian with apixaban in participants with atrial fibrillation or atrial flutter. Participants are randomly assigned to milvexian 100 mg or apixaban (5 mg or 2.5 mg per label indication) twice daily. The primary efficacy objective is to evaluate if milvexian is noninferior to apixaban for the prevention of stroke and systemic embolism. The principal safety objective is to evaluate if milvexian is superior to apixaban in reducing the endpoint of International Society of Thrombosis and Hemostasis (ISTH) major bleeding events and the composite endpoint of ISTH major and clinically relevant nonmajor (CRNM) bleeding events. In total, 15,500 participants from approximately 1,000 sites in over 30 countries are planned to be enrolled. They will be followed until both 430 primary efficacy outcome events and 530 principal safety events are observed, which is estimated to take approximately 4 years.</p></div><div><h3>Conclusion</h3><p>The LIBREXIA AF study will determine the efficacy and safety of the oral Factor XIa inhibitor milvexian compared with apixaban in participants with either atrial fibrillation or atrial flutter.</p></div><div><h3>Trial registration</h3><p>ClinicalTrials.gov NCT05757869</p></div>","PeriodicalId":7868,"journal":{"name":"American heart journal","volume":null,"pages":null},"PeriodicalIF":3.7,"publicationDate":"2024-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0002870324002060/pdfft?md5=9d5dedf46b35a702a85245f6480f289f&pid=1-s2.0-S0002870324002060-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142103692","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}