Min Hye Kang, Weon Kim, J. S. Kim, K. Jeong, M. Jeong, J. Hwang, S. Hur, H. Hwang
Background Hydrophilic and lipophilic statins have similar efficacies in treating coronary artery disease. However, specific factors relevant to renal impairment and different arterial pathogeneses could modify the clinical effects of statin lipophilicity, and create differences in protective effects between statin types in patients with renal impairment. Methods and Results A total of 2062 patients with acute myocardial infarction with an estimated glomerular filtration rate <60 mL/min per 1.73 m2 were enrolled from the Korea Acute Myocardial Infarction Registry between November 2011 and December 2015. The primary end point was a composite of 2‐year major adverse cardiac and cerebrovascular events (MACEs) after acute myocardial infarction occurrence. MACEs were defined as all‐cause death, recurrent myocardial infarction, revascularization, and stroke. Propensity‐score matching and Cox proportional hazards regression were performed. A total of 529 patients treated with hydrophilic statins were matched to 529 patients treated with lipophilic statins. There was no difference in the statin equivalent dose between the 2 statin groups. The cumulative event rate of MACEs, all‐cause mortality, and recurrent myocardial infarction were significantly lower in patients treated with hydrophilic statins in the propensity‐score matched population (all P<0.05). In the multivariable Cox regression analysis, patients treated with hydrophilic statins had a lower risk for composite MACEs (hazard ratio [HR], 0.70 [95% CI, 0.55–0.90]), all‐cause mortality (HR, 0.67 [95% CI, 0.49–0.93]), and recurrent myocardial infarction (HR, 0.40 [95% CI, 0.21–0.73]), but not for revascularization and ischemic stroke. Conclusions Hydrophilic statin treatment was associated with lower risk of MACEs and all‐cause mortality than lipophilic statin in a propensity‐score matched observational cohort of patients with renal impairment following acute myocardial infarction.
{"title":"Hydrophilic Versus Lipophilic Statin Treatments in Patients With Renal Impairment After Acute Myocardial Infarction","authors":"Min Hye Kang, Weon Kim, J. S. Kim, K. Jeong, M. Jeong, J. Hwang, S. Hur, H. Hwang","doi":"10.1161/JAHA.121.024649","DOIUrl":"https://doi.org/10.1161/JAHA.121.024649","url":null,"abstract":"Background Hydrophilic and lipophilic statins have similar efficacies in treating coronary artery disease. However, specific factors relevant to renal impairment and different arterial pathogeneses could modify the clinical effects of statin lipophilicity, and create differences in protective effects between statin types in patients with renal impairment. Methods and Results A total of 2062 patients with acute myocardial infarction with an estimated glomerular filtration rate <60 mL/min per 1.73 m2 were enrolled from the Korea Acute Myocardial Infarction Registry between November 2011 and December 2015. The primary end point was a composite of 2‐year major adverse cardiac and cerebrovascular events (MACEs) after acute myocardial infarction occurrence. MACEs were defined as all‐cause death, recurrent myocardial infarction, revascularization, and stroke. Propensity‐score matching and Cox proportional hazards regression were performed. A total of 529 patients treated with hydrophilic statins were matched to 529 patients treated with lipophilic statins. There was no difference in the statin equivalent dose between the 2 statin groups. The cumulative event rate of MACEs, all‐cause mortality, and recurrent myocardial infarction were significantly lower in patients treated with hydrophilic statins in the propensity‐score matched population (all P<0.05). In the multivariable Cox regression analysis, patients treated with hydrophilic statins had a lower risk for composite MACEs (hazard ratio [HR], 0.70 [95% CI, 0.55–0.90]), all‐cause mortality (HR, 0.67 [95% CI, 0.49–0.93]), and recurrent myocardial infarction (HR, 0.40 [95% CI, 0.21–0.73]), but not for revascularization and ischemic stroke. Conclusions Hydrophilic statin treatment was associated with lower risk of MACEs and all‐cause mortality than lipophilic statin in a propensity‐score matched observational cohort of patients with renal impairment following acute myocardial infarction.","PeriodicalId":17189,"journal":{"name":"Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease","volume":"287 ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"91457414","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Xiaonan Chen, Hao Lin, Weiyao Xiong, Jia-Yu Pan, Shuying Huang, Shan Xu, Shufang He, Ming Lei, A. C. Chang, Huili Zhang
Background Heart failure with preserved ejection fraction (HFpEF) accounts for 50% of patients with heart failure. Clinically, HFpEF prevalence shows age and gender biases. Although the majority of patients with HFpEF are elderly, there is an emergence of young patients with HFpEF. A better understanding of the underlying pathogenic mechanism is urgently needed. Here, we aimed to determine the role of aging in the pathogenesis of HFpEF. Methods and Results HFpEF dietary regimen (high‐fat diet + Nω‐Nitro‐L‐arginine methyl ester hydrochloride) was used to induce HFpEF in wild type and telomerase RNA knockout mice (second‐generation and third‐generation telomerase RNA component knockout), an aging murine model. First, both male and female animals develop HFpEF equally. Second, cardiac wall thickening preceded diastolic dysfunction in all HFpEF animals. Third, accelerated HFpEF onset was observed in second‐generation telomerase RNA component knockout (at 6 weeks) and third‐generation telomerase RNA component knockout (at 4 weeks) compared with wild type (8 weeks). Fourth, we demonstrate that mitochondrial respiration transitioned from compensatory state (normal basal yet loss of maximal respiratory capacity) to dysfunction (loss of both basal and maximal respiratory capacity) in a p53 dosage dependent manner. Last, using myocardial‐specific p53 knockout animals, we demonstrate that loss of p53 activation delays the development of HFpEF. Conclusions Here we demonstrate that p53 activation plays a role in the pathogenesis of HFpEF. We show that short telomere animals exhibit a basal level of p53 activation, mitochondria upregulate mtDNA encoded genes as a mean to compensate for blocked mitochondrial biogenesis, and loss of myocardial p53 delays HFpEF onset in high fat diet + Nω‐Nitro‐L‐arginine methyl ester hydrochloride challenged murine model.
背景:保留射血分数(HFpEF)的心力衰竭占心力衰竭患者的50%。临床上，HFpEF患病率存在年龄和性别差异。虽然大多数HFpEF患者是老年人，但也出现了年轻的HFpEF患者。迫切需要更好地了解潜在的致病机制。在这里，我们旨在确定衰老在HFpEF发病机制中的作用。方法与结果采用HFpEF饮食方案(高脂饮食+ Nω -硝基- L -精氨酸甲酯盐酸盐)诱导野生型和端粒酶RNA敲除小鼠(第二代和第三代端粒酶RNA成分敲除)衰老小鼠模型HFpEF。首先，雄性和雌性动物同样会患上HFpEF。其次，在所有HFpEF动物中，心脏壁增厚先于舒张功能障碍。第三，与野生型(8周)相比，第二代端粒酶RNA成分敲除组(6周)和第三代端粒酶RNA成分敲除组(4周)观察到HFpEF的加速发作。第四，我们证明了线粒体呼吸以p53剂量依赖的方式从代偿状态(正常的基础呼吸能力和最大呼吸能力的丧失)过渡到功能障碍(基础呼吸能力和最大呼吸能力的丧失)。最后，使用心肌特异性p53敲除动物，我们证明p53激活的丧失会延迟HFpEF的发展。结论p53的激活在HFpEF的发病机制中起作用。我们发现，短端粒动物表现出基础水平的p53激活，线粒体上调mtDNA编码基因作为补偿线粒体生物发生受阻的手段，心肌p53的缺失延迟了高脂肪饮食+ Nω -硝基- L -精氨酸甲酯盐化物挑战小鼠模型的HFpEF发病。
{"title":"p53‐Dependent Mitochondrial Compensation in Heart Failure With Preserved Ejection Fraction","authors":"Xiaonan Chen, Hao Lin, Weiyao Xiong, Jia-Yu Pan, Shuying Huang, Shan Xu, Shufang He, Ming Lei, A. C. Chang, Huili Zhang","doi":"10.1161/JAHA.121.024582","DOIUrl":"https://doi.org/10.1161/JAHA.121.024582","url":null,"abstract":"Background Heart failure with preserved ejection fraction (HFpEF) accounts for 50% of patients with heart failure. Clinically, HFpEF prevalence shows age and gender biases. Although the majority of patients with HFpEF are elderly, there is an emergence of young patients with HFpEF. A better understanding of the underlying pathogenic mechanism is urgently needed. Here, we aimed to determine the role of aging in the pathogenesis of HFpEF. Methods and Results HFpEF dietary regimen (high‐fat diet + Nω‐Nitro‐L‐arginine methyl ester hydrochloride) was used to induce HFpEF in wild type and telomerase RNA knockout mice (second‐generation and third‐generation telomerase RNA component knockout), an aging murine model. First, both male and female animals develop HFpEF equally. Second, cardiac wall thickening preceded diastolic dysfunction in all HFpEF animals. Third, accelerated HFpEF onset was observed in second‐generation telomerase RNA component knockout (at 6 weeks) and third‐generation telomerase RNA component knockout (at 4 weeks) compared with wild type (8 weeks). Fourth, we demonstrate that mitochondrial respiration transitioned from compensatory state (normal basal yet loss of maximal respiratory capacity) to dysfunction (loss of both basal and maximal respiratory capacity) in a p53 dosage dependent manner. Last, using myocardial‐specific p53 knockout animals, we demonstrate that loss of p53 activation delays the development of HFpEF. Conclusions Here we demonstrate that p53 activation plays a role in the pathogenesis of HFpEF. We show that short telomere animals exhibit a basal level of p53 activation, mitochondria upregulate mtDNA encoded genes as a mean to compensate for blocked mitochondrial biogenesis, and loss of myocardial p53 delays HFpEF onset in high fat diet + Nω‐Nitro‐L‐arginine methyl ester hydrochloride challenged murine model.","PeriodicalId":17189,"journal":{"name":"Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease","volume":"12 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"75233013","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
M. Segar, Kershaw V. Patel, A. Hellkamp, M. Vaduganathan, Y. Lokhnygina, Jennifer B. Green, S. Wan, A. Kolkailah, R. Holman, E. Peterson, V. Kannan, D. Willett, D. McGuire, A. Pandey
Background The WATCH‐DM (weight [body mass index], age, hypertension, creatinine, high‐density lipoprotein cholesterol, diabetes control [fasting plasma glucose], ECG QRS duration, myocardial infarction, and coronary artery bypass grafting) and TRS‐HFDM (Thrombolysis in Myocardial Infarction [TIMI] risk score for heart failure in diabetes) risk scores were developed to predict risk of heart failure (HF) among individuals with type 2 diabetes. WATCH‐DM was developed to predict incident HF, whereas TRS‐HFDM predicts HF hospitalization among patients with and without a prior HF history. We evaluated the model performance of both scores to predict incident HF events among patients with type 2 diabetes and no history of HF hospitalization across different cohorts and clinical settings with varying baseline risk. Methods and Results Incident HF risk was estimated by the integer‐based WATCH‐DM and TRS‐HFDM scores in participants with type 2 diabetes free of baseline HF from 2 randomized clinical trials (TECOS [Trial Evaluating Cardiovascular Outcomes With Sitagliptin], N=12 028; and Look AHEAD [Look Action for Health in Diabetes] trial, N=4867). The integer‐based WATCH‐DM score was also validated in electronic health record data from a single large health care system (N=7475). Model discrimination was assessed by the Harrell concordance index and calibration by the Greenwood‐Nam‐D’Agostino statistic. HF incidence rate was 7.5, 3.9, and 4.1 per 1000 person‐years in the TECOS, Look AHEAD trial, and electronic health record cohorts, respectively. Integer‐based WATCH‐DM and TRS‐HFDM scores had similar discrimination and calibration for predicting 5‐year HF risk in the Look AHEAD trial cohort (concordance indexes=0.70; Greenwood‐Nam‐D’Agostino P>0.30 for both). Both scores had lower discrimination and underpredicted HF risk in the TECOS cohort (concordance indexes=0.65 and 0.66, respectively; Greenwood‐Nam‐D’Agostino P<0.001 for both). In the electronic health record cohort, the integer‐based WATCH‐DM score demonstrated a concordance index of 0.73 with adequate calibration (Greenwood‐Nam‐D’Agostino P=0.96). TRS‐HFDM score could not be validated in the electronic health record because of unavailability of data on urine albumin/creatinine ratio in most patients in the contemporary clinical practice. Conclusions The WATCH‐DM and TRS‐HFDM risk scores can discriminate risk of HF among intermediate‐risk populations with type 2 diabetes.
{"title":"Validation of the WATCH‐DM and TRS‐HFDM Risk Scores to Predict the Risk of Incident Hospitalization for Heart Failure Among Adults With Type 2 Diabetes: A Multicohort Analysis","authors":"M. Segar, Kershaw V. Patel, A. Hellkamp, M. Vaduganathan, Y. Lokhnygina, Jennifer B. Green, S. Wan, A. Kolkailah, R. Holman, E. Peterson, V. Kannan, D. Willett, D. McGuire, A. Pandey","doi":"10.1161/JAHA.121.024094","DOIUrl":"https://doi.org/10.1161/JAHA.121.024094","url":null,"abstract":"Background The WATCH‐DM (weight [body mass index], age, hypertension, creatinine, high‐density lipoprotein cholesterol, diabetes control [fasting plasma glucose], ECG QRS duration, myocardial infarction, and coronary artery bypass grafting) and TRS‐HFDM (Thrombolysis in Myocardial Infarction [TIMI] risk score for heart failure in diabetes) risk scores were developed to predict risk of heart failure (HF) among individuals with type 2 diabetes. WATCH‐DM was developed to predict incident HF, whereas TRS‐HFDM predicts HF hospitalization among patients with and without a prior HF history. We evaluated the model performance of both scores to predict incident HF events among patients with type 2 diabetes and no history of HF hospitalization across different cohorts and clinical settings with varying baseline risk. Methods and Results Incident HF risk was estimated by the integer‐based WATCH‐DM and TRS‐HFDM scores in participants with type 2 diabetes free of baseline HF from 2 randomized clinical trials (TECOS [Trial Evaluating Cardiovascular Outcomes With Sitagliptin], N=12 028; and Look AHEAD [Look Action for Health in Diabetes] trial, N=4867). The integer‐based WATCH‐DM score was also validated in electronic health record data from a single large health care system (N=7475). Model discrimination was assessed by the Harrell concordance index and calibration by the Greenwood‐Nam‐D’Agostino statistic. HF incidence rate was 7.5, 3.9, and 4.1 per 1000 person‐years in the TECOS, Look AHEAD trial, and electronic health record cohorts, respectively. Integer‐based WATCH‐DM and TRS‐HFDM scores had similar discrimination and calibration for predicting 5‐year HF risk in the Look AHEAD trial cohort (concordance indexes=0.70; Greenwood‐Nam‐D’Agostino P>0.30 for both). Both scores had lower discrimination and underpredicted HF risk in the TECOS cohort (concordance indexes=0.65 and 0.66, respectively; Greenwood‐Nam‐D’Agostino P<0.001 for both). In the electronic health record cohort, the integer‐based WATCH‐DM score demonstrated a concordance index of 0.73 with adequate calibration (Greenwood‐Nam‐D’Agostino P=0.96). TRS‐HFDM score could not be validated in the electronic health record because of unavailability of data on urine albumin/creatinine ratio in most patients in the contemporary clinical practice. Conclusions The WATCH‐DM and TRS‐HFDM risk scores can discriminate risk of HF among intermediate‐risk populations with type 2 diabetes.","PeriodicalId":17189,"journal":{"name":"Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease","volume":"10 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"74530878","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
M. Ribeiro, Carlos M Campos, Lucio T. Padilla, A. C. B. da Silva, J. E. T. de Paula, Marco A. Alcántara, Ricardo Santiago, Franklin Hanna, Franciele R da Silva, Karlyse C Belli, L. Azzalini, P. P. de Oliveira, G. Araujo, V. Sucato, K. Mashayekhi, A. Galassi, A. Abizaid, A. Quadros
Background Coronary perforation is a life‐threatening complication of acute percutaneous coronary intervention (PCI) for chronic total occlusions (CTO), but data on midterm outcomes are limited. Methods and Results Data from LATAM (Latin American)‐CTO Registry (57 centers; 9 countries) were analyzed. We assessed the risk of 30‐day, 1‐year major adverse cardiac events of coronary perforation using time‐to‐event and weighted composite end point analysis having CTO PCI without perforation as comparators. Additionally, we studied the independent predictors of perforation in these patients. Of 2054 patients who underwent CTO PCI between 2015 and 2018, the median Multicenter CTO Registry in Japan and Prospective Global Registry for the Study of Chronic Total Occlusion Intervention‐Chronic total occlusions scores were 2.0 (1.0–3.0) and 1.0 (0.0–2.0), respectively. The perforation rate was 3.7%, of which 55% were Ellis class 1. After 1‐year coronary perforation had higher major adverse cardiac events rates (24.9% versus 13.3%; P<0.01). Using weighted composite end point, perforation was associated with increased bleeding and ischemic events at 6 months (P=0.04) and 1 year (P<0.01). We found as independent predictors associated with coronary perforation during CTO PCI: maximum activated clotting time (P<0.01), Multicenter CTO Registry in Japan score ≥2 (P=0.05), antegrade knuckle wire (P=0.04), and right coronary artery CTO PCI (P=0.05). Conclusions Coronary perforation was infrequent and associated with anatomical and procedural complexity, resulting in higher risk of hemorrhagic and ischemic events. Landmark and weighted analysis showed a sustained burden of major events between 6 months and 1 year follow‐up.
{"title":"Risk Burden of Coronary Perforation in Chronic Total Occlusion Recanalization: Latin American CTO Registry Analysis","authors":"M. Ribeiro, Carlos M Campos, Lucio T. Padilla, A. C. B. da Silva, J. E. T. de Paula, Marco A. Alcántara, Ricardo Santiago, Franklin Hanna, Franciele R da Silva, Karlyse C Belli, L. Azzalini, P. P. de Oliveira, G. Araujo, V. Sucato, K. Mashayekhi, A. Galassi, A. Abizaid, A. Quadros","doi":"10.1161/JAHA.121.024815","DOIUrl":"https://doi.org/10.1161/JAHA.121.024815","url":null,"abstract":"Background Coronary perforation is a life‐threatening complication of acute percutaneous coronary intervention (PCI) for chronic total occlusions (CTO), but data on midterm outcomes are limited. Methods and Results Data from LATAM (Latin American)‐CTO Registry (57 centers; 9 countries) were analyzed. We assessed the risk of 30‐day, 1‐year major adverse cardiac events of coronary perforation using time‐to‐event and weighted composite end point analysis having CTO PCI without perforation as comparators. Additionally, we studied the independent predictors of perforation in these patients. Of 2054 patients who underwent CTO PCI between 2015 and 2018, the median Multicenter CTO Registry in Japan and Prospective Global Registry for the Study of Chronic Total Occlusion Intervention‐Chronic total occlusions scores were 2.0 (1.0–3.0) and 1.0 (0.0–2.0), respectively. The perforation rate was 3.7%, of which 55% were Ellis class 1. After 1‐year coronary perforation had higher major adverse cardiac events rates (24.9% versus 13.3%; P<0.01). Using weighted composite end point, perforation was associated with increased bleeding and ischemic events at 6 months (P=0.04) and 1 year (P<0.01). We found as independent predictors associated with coronary perforation during CTO PCI: maximum activated clotting time (P<0.01), Multicenter CTO Registry in Japan score ≥2 (P=0.05), antegrade knuckle wire (P=0.04), and right coronary artery CTO PCI (P=0.05). Conclusions Coronary perforation was infrequent and associated with anatomical and procedural complexity, resulting in higher risk of hemorrhagic and ischemic events. Landmark and weighted analysis showed a sustained burden of major events between 6 months and 1 year follow‐up.","PeriodicalId":17189,"journal":{"name":"Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease","volume":"96 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"73884229","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
M. Nelson, Olivia N. Gilbert, P. Duncan, D. Kitzman, G. Reeves, D. Whellan, R. Mentz, Haiying Chen, L. Hewston, Karen M Taylor, A. Pastva
Background The REHAB‐HF (Rehabilitation Therapy in Older Acute Heart Failure Patients) trial showed that a novel, early, transitional, tailored, progressive, multidomain physical rehabilitation intervention improved physical function and quality of life in older, frail patients hospitalized for acute decompensated heart failure. This analysis examined the relationship between intervention adherence and outcomes. Methods and Results Adherence was defined as percent of sessions attended and percent of sessions attended adjusted for missed sessions for medical reasons. Baseline characteristics were examined to identify predictors of session attendance. Associations of session attendance with change in physical function (Short Physical Performance Battery [primary outcome], 6‐minute walk distance, quality of life [Kansas City Cardiomyopathy Questionnaire], depression, and clinical events [landmarked postintervention]) were examined in multivariate analyses. Adherence was 67%±34%, and adherence adjusted for missed sessions for medical reasons was 78%±34%. Independent predictors of higher session attendance were the following: nonsmoking, absence of myocardial infarction history and depression, and higher baseline Short Physical Performance Battery. After adjustment for predictors, adherence was significantly associated with larger increases in Short Physical Performance Battery (parameter estimate: β=0.06[0.03–0.10], P=0.001), 6‐minute walk distance (β=1.8[0.2–3.5], P=0.032), and Kansas City Cardiomyopathy Questionnaire score (β=0.62[0.26–0.98], P=0.001), and reduction in depression (β=−0.08[−0.12 to 0.04], P<0.001). Additionally, higher adherence was significantly associated with reduced 6‐month all‐cause rehospitalization (rate ratio: 0.97 [0.95–0.99], P=0.020), combined all‐cause rehospitalization and death (0.97 [0.95–0.99], P=0.017), and all‐cause rehospitalization days (0.96 [0.94–0.99], P=0.004) postintervention. Conclusions In older, frail patients with acute decompensated heart failure, higher adherence was significantly associated with improved patient‐centered and clinical event outcomes. These data support the efficacy of the comprehensive adherence plan and the subsequent intervention‐related benefits observed in REHAB‐HF. Registration URL: https://clinicaltrials.gov/; Unique identifier: NCT02196038.
{"title":"Intervention Adherence in REHAB‐HF: Predictors and Relationship With Physical Function, Quality of Life, and Clinical Events","authors":"M. Nelson, Olivia N. Gilbert, P. Duncan, D. Kitzman, G. Reeves, D. Whellan, R. Mentz, Haiying Chen, L. Hewston, Karen M Taylor, A. Pastva","doi":"10.1161/JAHA.121.024246","DOIUrl":"https://doi.org/10.1161/JAHA.121.024246","url":null,"abstract":"Background The REHAB‐HF (Rehabilitation Therapy in Older Acute Heart Failure Patients) trial showed that a novel, early, transitional, tailored, progressive, multidomain physical rehabilitation intervention improved physical function and quality of life in older, frail patients hospitalized for acute decompensated heart failure. This analysis examined the relationship between intervention adherence and outcomes. Methods and Results Adherence was defined as percent of sessions attended and percent of sessions attended adjusted for missed sessions for medical reasons. Baseline characteristics were examined to identify predictors of session attendance. Associations of session attendance with change in physical function (Short Physical Performance Battery [primary outcome], 6‐minute walk distance, quality of life [Kansas City Cardiomyopathy Questionnaire], depression, and clinical events [landmarked postintervention]) were examined in multivariate analyses. Adherence was 67%±34%, and adherence adjusted for missed sessions for medical reasons was 78%±34%. Independent predictors of higher session attendance were the following: nonsmoking, absence of myocardial infarction history and depression, and higher baseline Short Physical Performance Battery. After adjustment for predictors, adherence was significantly associated with larger increases in Short Physical Performance Battery (parameter estimate: β=0.06[0.03–0.10], P=0.001), 6‐minute walk distance (β=1.8[0.2–3.5], P=0.032), and Kansas City Cardiomyopathy Questionnaire score (β=0.62[0.26–0.98], P=0.001), and reduction in depression (β=−0.08[−0.12 to 0.04], P<0.001). Additionally, higher adherence was significantly associated with reduced 6‐month all‐cause rehospitalization (rate ratio: 0.97 [0.95–0.99], P=0.020), combined all‐cause rehospitalization and death (0.97 [0.95–0.99], P=0.017), and all‐cause rehospitalization days (0.96 [0.94–0.99], P=0.004) postintervention. Conclusions In older, frail patients with acute decompensated heart failure, higher adherence was significantly associated with improved patient‐centered and clinical event outcomes. These data support the efficacy of the comprehensive adherence plan and the subsequent intervention‐related benefits observed in REHAB‐HF. Registration URL: https://clinicaltrials.gov/; Unique identifier: NCT02196038.","PeriodicalId":17189,"journal":{"name":"Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease","volume":"99 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"76077024","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
T. Gallo, C. Heise, R. Woosley, J. Tisdale, Malinda S. Tan, S. Gephart, Corneliu C Antonescu, D. Malone
Background Torsade de pointes (TdP) is a potentially fatal cardiac arrhythmia that is often drug induced. Clinical decision support (CDS) may help minimize TdP risk by guiding decision making in patients at risk. CDS has been shown to decrease prescribing of high‐risk medications in patients at risk of TdP, but alerts are often ignored. Other risk‐management options can potentially be incorporated in TdP risk CDS. Our goal was to evaluate actions clinicians take in response to a CDS advisory that uses a modified Tisdale QT risk score and presents management options that are easily selected (eg, single click). Methods and Results We implemented an inpatient TdP risk advisory systemwide across a large health care system comprising 30 hospitals. This CDS was programmed to appear when prescribers attempted ordering medications with a known risk of TdP in a patient with a QT risk score ≥12. The CDS displayed patient‐specific information and offered relevant management options including canceling offending medications and ordering electrolyte replacement protocols or ECGs. We retrospectively studied the actions clinicians took within the advisory and separated by drug class. During an 8‐month period, 7794 TdP risk advisories were issued. Antibiotics were the most frequent trigger of the advisory (n=2578, 33.1%). At least 1 action was taken within the advisory window for 2700 (34.6%) of the advisories. The most frequent action taken was ordering an ECG (n=1584, 20.3%). Incoming medication orders were canceled in 793 (10.2%) of the advisories. The frequency of each action taken varied by drug class (P<0.05 for all actions). Conclusions A modified Tisdale QT risk score–based CDS that offered relevant single‐click management options yielded a high action/response rate. Actions taken by clinicians varied depending on the class of the medication that evoked the TdP risk advisory, but the most frequent was ordering an ECG.
{"title":"Clinician Responses to a Clinical Decision Support Advisory for High Risk of Torsades de Pointes","authors":"T. Gallo, C. Heise, R. Woosley, J. Tisdale, Malinda S. Tan, S. Gephart, Corneliu C Antonescu, D. Malone","doi":"10.1161/JAHA.122.024338","DOIUrl":"https://doi.org/10.1161/JAHA.122.024338","url":null,"abstract":"Background Torsade de pointes (TdP) is a potentially fatal cardiac arrhythmia that is often drug induced. Clinical decision support (CDS) may help minimize TdP risk by guiding decision making in patients at risk. CDS has been shown to decrease prescribing of high‐risk medications in patients at risk of TdP, but alerts are often ignored. Other risk‐management options can potentially be incorporated in TdP risk CDS. Our goal was to evaluate actions clinicians take in response to a CDS advisory that uses a modified Tisdale QT risk score and presents management options that are easily selected (eg, single click). Methods and Results We implemented an inpatient TdP risk advisory systemwide across a large health care system comprising 30 hospitals. This CDS was programmed to appear when prescribers attempted ordering medications with a known risk of TdP in a patient with a QT risk score ≥12. The CDS displayed patient‐specific information and offered relevant management options including canceling offending medications and ordering electrolyte replacement protocols or ECGs. We retrospectively studied the actions clinicians took within the advisory and separated by drug class. During an 8‐month period, 7794 TdP risk advisories were issued. Antibiotics were the most frequent trigger of the advisory (n=2578, 33.1%). At least 1 action was taken within the advisory window for 2700 (34.6%) of the advisories. The most frequent action taken was ordering an ECG (n=1584, 20.3%). Incoming medication orders were canceled in 793 (10.2%) of the advisories. The frequency of each action taken varied by drug class (P<0.05 for all actions). Conclusions A modified Tisdale QT risk score–based CDS that offered relevant single‐click management options yielded a high action/response rate. Actions taken by clinicians varied depending on the class of the medication that evoked the TdP risk advisory, but the most frequent was ordering an ECG.","PeriodicalId":17189,"journal":{"name":"Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease","volume":"165 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"76552627","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
B. Shahim, B. Redfors, B. Lindman, Shmuel Chen, T. Dahlén, Tamim Nazif, S. Kapadia, Z. Gertz, Aaron Crowley, Ditian Li, V. Thourani, S. Kodali, A. Zajarías, V. Babaliaros, R. Guyton, S. Elmariah, H. Herrmann, D. Cohen, M. Mack, Craig R. Smith, M. Leon, I. George
Background The neutrophil‐to‐lymphocyte ratio (NLR) as a marker of systemic inflammation has been associated with worse prognosis in several chronic disease states, including heart failure. However, few data exist on the prognostic impact of elevated baseline NLR or change in NLR levels during follow‐up in patients undergoing transcatheter or surgical aortic valve replacement (TAVR or SAVR) for aortic stenosis. Methods and Results NLR was available in 5881 patients with severe aortic stenosis receiving TAVR or SAVR in PARTNER (Placement of Aortic Transcatheter Valves) I, II, and S3 trials/registries (median [Q1, Q3] NLR, 3.30 [2.40, 4.90]); mean NLR, 4.10; range, 0.5–24.9) and was evaluated as continuous variable and categorical tertiles (low: NLR ≤2.70, n=1963; intermediate: NLR 2.70–4.20, n=1958; high: NLR ≥4.20, n=1960). No patients had known baseline infection. High baseline NLR was associated with increased risk of death or rehospitalization at 3 years (58.4% versus 41.0%; adjusted hazard ratio [aHR], 1.39; 95% CI, 1.18–1.63; P<0.0001) compared with those with low NLR, irrespective of treatment modality. In both patients treated with TAVR and patients treated with SAVR, NLR decreased between baseline and 2 years. A 1‐unit observed decrease in NLR between baseline and 1 year was associated with lower risk of death or rehospitalization between 1 year and 3 years (aHR, 0.86; 95% CI, 0.82–0.89; P<0.0001). Conclusions Elevated baseline NLR was independently associated with increased subsequent mortality and rehospitalization after TAVR or SAVR. The observed decrease in NLR after TAVR or SAVR was associated with improved outcomes. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT00530894, NCT0134313, NCT02184442, NCT03225001, NCT0322141.
{"title":"Neutrophil‐to‐Lymphocyte Ratios in Patients Undergoing Aortic Valve Replacement: The PARTNER Trials and Registries","authors":"B. Shahim, B. Redfors, B. Lindman, Shmuel Chen, T. Dahlén, Tamim Nazif, S. Kapadia, Z. Gertz, Aaron Crowley, Ditian Li, V. Thourani, S. Kodali, A. Zajarías, V. Babaliaros, R. Guyton, S. Elmariah, H. Herrmann, D. Cohen, M. Mack, Craig R. Smith, M. Leon, I. George","doi":"10.1161/JAHA.121.024091","DOIUrl":"https://doi.org/10.1161/JAHA.121.024091","url":null,"abstract":"Background The neutrophil‐to‐lymphocyte ratio (NLR) as a marker of systemic inflammation has been associated with worse prognosis in several chronic disease states, including heart failure. However, few data exist on the prognostic impact of elevated baseline NLR or change in NLR levels during follow‐up in patients undergoing transcatheter or surgical aortic valve replacement (TAVR or SAVR) for aortic stenosis. Methods and Results NLR was available in 5881 patients with severe aortic stenosis receiving TAVR or SAVR in PARTNER (Placement of Aortic Transcatheter Valves) I, II, and S3 trials/registries (median [Q1, Q3] NLR, 3.30 [2.40, 4.90]); mean NLR, 4.10; range, 0.5–24.9) and was evaluated as continuous variable and categorical tertiles (low: NLR ≤2.70, n=1963; intermediate: NLR 2.70–4.20, n=1958; high: NLR ≥4.20, n=1960). No patients had known baseline infection. High baseline NLR was associated with increased risk of death or rehospitalization at 3 years (58.4% versus 41.0%; adjusted hazard ratio [aHR], 1.39; 95% CI, 1.18–1.63; P<0.0001) compared with those with low NLR, irrespective of treatment modality. In both patients treated with TAVR and patients treated with SAVR, NLR decreased between baseline and 2 years. A 1‐unit observed decrease in NLR between baseline and 1 year was associated with lower risk of death or rehospitalization between 1 year and 3 years (aHR, 0.86; 95% CI, 0.82–0.89; P<0.0001). Conclusions Elevated baseline NLR was independently associated with increased subsequent mortality and rehospitalization after TAVR or SAVR. The observed decrease in NLR after TAVR or SAVR was associated with improved outcomes. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT00530894, NCT0134313, NCT02184442, NCT03225001, NCT0322141.","PeriodicalId":17189,"journal":{"name":"Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease","volume":"16 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"91212986","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Hao Zhang, K. Jamieson, J. Grenier, A. Nikhanj, Zeyu Tang, Faqi Wang, Shaohua Wang, J. Seidman, C. Seidman, R. Thompson, J. Seubert, G. Oudit
Background Myocardial iron deficiency (MID) in heart failure (HF) remains largely unexplored. We aim to establish defining criterion for MID, evaluate its pathophysiological role, and evaluate the applicability of monitoring it non‐invasively in human explanted hearts. Methods and Results Biventricular tissue iron levels were measured in both failing (n=138) and non‐failing control (NFC, n=46) explanted human hearts. Clinical phenotyping was complemented with comprehensive assessment of myocardial remodeling and mitochondrial functional profiles, including metabolic and oxidative stress. Myocardial iron status was further investigated by cardiac magnetic resonance imaging. Myocardial iron content in the left ventricle was lower in HF versus NFC (121.4 [88.1–150.3] versus 137.4 [109.2–165.9] μg/g dry weight), which was absent in the right ventricle. With a priori cutoff of 86.1 μg/g d.w. in left ventricle, we identified 23% of HF patients with MID (HF‐MID) associated with higher NYHA class and worsened left ventricle function. Respiratory chain and Krebs cycle enzymatic activities were suppressed and strongly correlated with depleted iron stores in HF‐MID hearts. Defenses against oxidative stress were severely impaired in association with worsened adverse remodeling in iron‐deficient hearts. Mechanistically, iron uptake pathways were impeded in HF‐MID including decreased translocation to the sarcolemma, while transmembrane fraction of ferroportin positively correlated with MID. Cardiac magnetic resonance with T2* effectively captured myocardial iron levels in failing hearts. Conclusions MID is highly prevalent in advanced human HF and exacerbates pathological remodeling in HF driven primarily by dysfunctional mitochondria and increased oxidative stress in the left ventricle. Cardiac magnetic resonance demonstrates clinical potential to non‐invasively monitor MID.
{"title":"Myocardial Iron Deficiency and Mitochondrial Dysfunction in Advanced Heart Failure in Humans","authors":"Hao Zhang, K. Jamieson, J. Grenier, A. Nikhanj, Zeyu Tang, Faqi Wang, Shaohua Wang, J. Seidman, C. Seidman, R. Thompson, J. Seubert, G. Oudit","doi":"10.1161/JAHA.121.022853","DOIUrl":"https://doi.org/10.1161/JAHA.121.022853","url":null,"abstract":"Background Myocardial iron deficiency (MID) in heart failure (HF) remains largely unexplored. We aim to establish defining criterion for MID, evaluate its pathophysiological role, and evaluate the applicability of monitoring it non‐invasively in human explanted hearts. Methods and Results Biventricular tissue iron levels were measured in both failing (n=138) and non‐failing control (NFC, n=46) explanted human hearts. Clinical phenotyping was complemented with comprehensive assessment of myocardial remodeling and mitochondrial functional profiles, including metabolic and oxidative stress. Myocardial iron status was further investigated by cardiac magnetic resonance imaging. Myocardial iron content in the left ventricle was lower in HF versus NFC (121.4 [88.1–150.3] versus 137.4 [109.2–165.9] μg/g dry weight), which was absent in the right ventricle. With a priori cutoff of 86.1 μg/g d.w. in left ventricle, we identified 23% of HF patients with MID (HF‐MID) associated with higher NYHA class and worsened left ventricle function. Respiratory chain and Krebs cycle enzymatic activities were suppressed and strongly correlated with depleted iron stores in HF‐MID hearts. Defenses against oxidative stress were severely impaired in association with worsened adverse remodeling in iron‐deficient hearts. Mechanistically, iron uptake pathways were impeded in HF‐MID including decreased translocation to the sarcolemma, while transmembrane fraction of ferroportin positively correlated with MID. Cardiac magnetic resonance with T2* effectively captured myocardial iron levels in failing hearts. Conclusions MID is highly prevalent in advanced human HF and exacerbates pathological remodeling in HF driven primarily by dysfunctional mitochondria and increased oxidative stress in the left ventricle. Cardiac magnetic resonance demonstrates clinical potential to non‐invasively monitor MID.","PeriodicalId":17189,"journal":{"name":"Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease","volume":"26 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"91029731","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
In this issue of the Journal of the American Heart Association (JAHA), Zhang and colleagues1 have reported that the intake of omega3 (ω3) polyunsaturated fatty acids (PUFAs), docosahexaenoic acid (DHA), and eicosapentaenoic acid (EPA) are associated with a reduction in blood pressure (BP) and identified the optimal dose of 2 to 3 g/d. Although these findings are not entirely novel, they are robust and provide insights into the longstanding debate on the role of ω3 PUFAs in modifying cardiovascular risk.
{"title":"Blood Pressure–Lowering Effects of Omega‐3 Polyunsaturated Fatty Acids: Are These the Missing Link to Explain the Relationship Between Omega‐3 Polyunsaturated Fatty Acids and Cardiovascular Disease?","authors":"M. George, Ajay K. Gupta","doi":"10.1161/JAHA.121.026258","DOIUrl":"https://doi.org/10.1161/JAHA.121.026258","url":null,"abstract":"In this issue of the Journal of the American Heart Association (JAHA), Zhang and colleagues1 have reported that the intake of omega3 (ω3) polyunsaturated fatty acids (PUFAs), docosahexaenoic acid (DHA), and eicosapentaenoic acid (EPA) are associated with a reduction in blood pressure (BP) and identified the optimal dose of 2 to 3 g/d. Although these findings are not entirely novel, they are robust and provide insights into the longstanding debate on the role of ω3 PUFAs in modifying cardiovascular risk.","PeriodicalId":17189,"journal":{"name":"Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease","volume":"2 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"91132709","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-06-01DOI: 10.1016/j.jpainsymman.2022.04.117
C. Graham, R. Schonnop, T. Killackey, D. Kavalieratos, S. Bush, L. Steinberg, Susanna Mak, Kieran Quinn, S. Isenberg
{"title":"Exploring Health Care Providers' Experiences of Providing Collaborative Palliative Care for Patients With Advanced Heart Failure At Home: A Qualitative Study","authors":"C. Graham, R. Schonnop, T. Killackey, D. Kavalieratos, S. Bush, L. Steinberg, Susanna Mak, Kieran Quinn, S. Isenberg","doi":"10.1016/j.jpainsymman.2022.04.117","DOIUrl":"https://doi.org/10.1016/j.jpainsymman.2022.04.117","url":null,"abstract":"","PeriodicalId":17189,"journal":{"name":"Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease","volume":"126 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"80669049","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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