Monil Majmundar, Gabriel Ibarra, Ashish Kumar, Rajkumar Doshi, Palak Shah, Roxana Mehran, Grant W Reed, Rishi Puri, Samir R Kapadia, Sripal Bangalore, Ankur Kalra
Background The role of invasive management compared with medical management in patients with non-ST-segment-elevation myocardial infarction (NSTEMI) and advanced chronic kidney disease (CKD) is uncertain, given the increased risk of procedural complications in patients with CKD. We aimed to compare clinical outcomes of invasive management with medical management in patients with NSTEMI-CKD. Methods and Results We identified NSTEMI and CKD stages 3, 4, 5, and end-stage renal disease admissions using International Classification of Diseases, Tenth Revision, Clinical Modification (ICD-10-CM) codes from the Nationwide Readmission Database 2016 to 2018. Patients were stratified into invasive and medical management. Primary outcome was mortality (in-hospital and 6 months after discharge). Secondary outcomes were in-hospital postprocedural complications (acute kidney injury requiring dialysis, major bleeding) and postdischarge 6-month safety and major adverse cardiovascular events. Out of 141 052 patients with NSTEMI-CKD, 85 875 (60.9%) were treated with invasive management, whereas 55 177 (39.1%) patients were managed medically. In propensity-score matched cohorts, invasive strategy was associated with lower in-hospital (CKD 3: odds ratio [OR], 0.47 [95% CI, 0.43-0.51]; P<0.001; CKD 4: OR, 0.79 [95% CI, 0.69-0.89]; P<0.001; CKD 5: OR, 0.72 [95% CI, 0.49-1.06]; P=0.096; end-stage renal disease: OR, 0.51 [95% CI, 0.46-0.56]; P<0.001) and 6-month mortality. Invasive management was associated with higher in-hospital postprocedural complications but no difference in postdischarge safety outcomes. Invasive management was associated with a lower hazard of major adverse cardiovascular events at 6 months in all CKD groups compared with medical management. Conclusions Invasive management was associated with lower mortality and major adverse cardiovascular events but minimal increased in-hospital complications in patients with NSTEMI-CKD compared with medical management, suggesting patients with NSTEMI-CKD should be offered invasive management.
{"title":"Invasive Versus Medical Management in Patients With Chronic Kidney Disease and Non-ST-Segment-Elevation Myocardial Infarction.","authors":"Monil Majmundar, Gabriel Ibarra, Ashish Kumar, Rajkumar Doshi, Palak Shah, Roxana Mehran, Grant W Reed, Rishi Puri, Samir R Kapadia, Sripal Bangalore, Ankur Kalra","doi":"10.1161/JAHA.121.025205","DOIUrl":"10.1161/JAHA.121.025205","url":null,"abstract":"<p><p>Background The role of invasive management compared with medical management in patients with non-ST-segment-elevation myocardial infarction (NSTEMI) and advanced chronic kidney disease (CKD) is uncertain, given the increased risk of procedural complications in patients with CKD. We aimed to compare clinical outcomes of invasive management with medical management in patients with NSTEMI-CKD. Methods and Results We identified NSTEMI and CKD stages 3, 4, 5, and end-stage renal disease admissions using <i>International Classification of Diseases, Tenth Revision, Clinical Modification</i> (<i>ICD-10-CM</i>) codes from the Nationwide Readmission Database 2016 to 2018. Patients were stratified into invasive and medical management. Primary outcome was mortality (in-hospital and 6 months after discharge). Secondary outcomes were in-hospital postprocedural complications (acute kidney injury requiring dialysis, major bleeding) and postdischarge 6-month safety and major adverse cardiovascular events. Out of 141 052 patients with NSTEMI-CKD, 85 875 (60.9%) were treated with invasive management, whereas 55 177 (39.1%) patients were managed medically. In propensity-score matched cohorts, invasive strategy was associated with lower in-hospital (CKD 3: odds ratio [OR], 0.47 [95% CI, 0.43-0.51]; <i>P</i><0.001; CKD 4: OR, 0.79 [95% CI, 0.69-0.89]; <i>P</i><0.001; CKD 5: OR, 0.72 [95% CI, 0.49-1.06]; <i>P</i>=0.096; end-stage renal disease: OR, 0.51 [95% CI, 0.46-0.56]; <i>P</i><0.001) and 6-month mortality. Invasive management was associated with higher in-hospital postprocedural complications but no difference in postdischarge safety outcomes. Invasive management was associated with a lower hazard of major adverse cardiovascular events at 6 months in all CKD groups compared with medical management. Conclusions Invasive management was associated with lower mortality and major adverse cardiovascular events but minimal increased in-hospital complications in patients with NSTEMI-CKD compared with medical management, suggesting patients with NSTEMI-CKD should be offered invasive management.</p>","PeriodicalId":17189,"journal":{"name":"Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2022-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9238658/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"77148760","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Invasive Management for Non-ST-Segment-Elevation Myocardial Infarction and Chronic Kidney Disease: Does One Size Fit All?","authors":"Ayman Elbadawi, Islam Y Elgendy, Paul Kumfa","doi":"10.1161/JAHA.122.026390","DOIUrl":"10.1161/JAHA.122.026390","url":null,"abstract":"","PeriodicalId":17189,"journal":{"name":"Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2022-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9238646/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"88117805","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
S. Zahid, M. Khan, S. Gowda, N. Faza, M. Honigberg, A. Vaught, C. Guan, A. Minhas, E. Michos
Background Women with polycystic ovary syndrome (PCOS) have an increased risk of pregnancy‐associated complications. However, data on peripartum cardiovascular complications remain limited. Hence, we investigated trends, outcomes, and predictors of cardiovascular complications associated with PCOS diagnosis during delivery hospitalizations in the United States. Methods and Results We used data from the National Inpatient Sample (2002–2019). International Classification of Diseases, Ninth Revision (ICD‐9), or International Classification of Diseases, Tenth Revision (ICD‐10), codes were used to identify delivery hospitalizations and PCOS diagnosis. A total of 71 436 308 weighted hospitalizations for deliveries were identified, of which 0.3% were among women with PCOS (n=195 675). The prevalence of PCOS, and obesity among those with PCOS, increased during the study period. Women with PCOS were older (median, 31 versus 28 years; P<0.01) and had a higher prevalence of diabetes, obesity, and dyslipidemia. After adjustment for age, race and ethnicity, comorbidities, insurance, and income, PCOS remained an independent predictor of cardiovascular complications, including preeclampsia (adjusted odds ratio [OR], 1.56 [95% CI, 1.54–1.59]; P<0.01), eclampsia (adjusted OR, 1.58 [95% CI, 1.54–1.59]; P<0.01), peripartum cardiomyopathy (adjusted OR, 1.79 [95% CI, 1.49–2.13]; P<0.01), and heart failure (adjusted OR, 1.76 [95% CI, 1.27–2.45]; P<0.01), compared with no PCOS. Moreover, delivery hospitalizations among women with PCOS were associated with increased length (3 versus 2 days; P<0.01) and cost of hospitalization ($4901 versus $3616; P<0.01). Conclusions Women with PCOS had a higher risk of preeclampsia/eclampsia, peripartum cardiomyopathy, and heart failure during delivery hospitalizations. Moreover, delivery hospitalizations among women with PCOS diagnosis were associated with increased length and cost of hospitalization. This signifies the importance of prepregnancy consultation and optimization for cardiometabolic health to improve maternal and neonatal outcomes.
{"title":"Trends, Predictors, and Outcomes of Cardiovascular Complications Associated With Polycystic Ovary Syndrome During Delivery Hospitalizations: A National Inpatient Sample Analysis (2002–2019)","authors":"S. Zahid, M. Khan, S. Gowda, N. Faza, M. Honigberg, A. Vaught, C. Guan, A. Minhas, E. Michos","doi":"10.1161/JAHA.121.025839","DOIUrl":"https://doi.org/10.1161/JAHA.121.025839","url":null,"abstract":"Background Women with polycystic ovary syndrome (PCOS) have an increased risk of pregnancy‐associated complications. However, data on peripartum cardiovascular complications remain limited. Hence, we investigated trends, outcomes, and predictors of cardiovascular complications associated with PCOS diagnosis during delivery hospitalizations in the United States. Methods and Results We used data from the National Inpatient Sample (2002–2019). International Classification of Diseases, Ninth Revision (ICD‐9), or International Classification of Diseases, Tenth Revision (ICD‐10), codes were used to identify delivery hospitalizations and PCOS diagnosis. A total of 71 436 308 weighted hospitalizations for deliveries were identified, of which 0.3% were among women with PCOS (n=195 675). The prevalence of PCOS, and obesity among those with PCOS, increased during the study period. Women with PCOS were older (median, 31 versus 28 years; P<0.01) and had a higher prevalence of diabetes, obesity, and dyslipidemia. After adjustment for age, race and ethnicity, comorbidities, insurance, and income, PCOS remained an independent predictor of cardiovascular complications, including preeclampsia (adjusted odds ratio [OR], 1.56 [95% CI, 1.54–1.59]; P<0.01), eclampsia (adjusted OR, 1.58 [95% CI, 1.54–1.59]; P<0.01), peripartum cardiomyopathy (adjusted OR, 1.79 [95% CI, 1.49–2.13]; P<0.01), and heart failure (adjusted OR, 1.76 [95% CI, 1.27–2.45]; P<0.01), compared with no PCOS. Moreover, delivery hospitalizations among women with PCOS were associated with increased length (3 versus 2 days; P<0.01) and cost of hospitalization ($4901 versus $3616; P<0.01). Conclusions Women with PCOS had a higher risk of preeclampsia/eclampsia, peripartum cardiomyopathy, and heart failure during delivery hospitalizations. Moreover, delivery hospitalizations among women with PCOS diagnosis were associated with increased length and cost of hospitalization. This signifies the importance of prepregnancy consultation and optimization for cardiometabolic health to improve maternal and neonatal outcomes.","PeriodicalId":17189,"journal":{"name":"Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2022-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"84207401","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}
Yunjin Yum, S. Shin, Hakje Yoo, Yong Hyun Kim, Eung Ju Kim, G. Lip, H. J. Joo
Background Improved prediction of atrial fibrillation (AF) may allow for earlier interventions for stroke prevention, as well as mortality and morbidity from other AF‐related complications. We developed a clinically feasible and accurate AF prediction model using electronic health records and computerized ECG interpretation. Methods and Results A total of 671 318 patients were screened from 3 tertiary hospitals. After careful exclusion of cases with missing values and a prior AF diagnosis, AF prediction models were developed from the derivation cohort of 25 584 patients without AF at baseline. In the internal/external validation cohort of 117 523 patients, the model using 6 clinical features and 5 ECG diagnoses showed the highest performance for 3‐year new‐onset AF prediction (C‐statistic, 0.796 [95% CI, 0.785–0.806]). A more simplified model using age, sex, and 5 ECG diagnoses (atrioventricular block, fusion beats, marked sinus arrhythmia, supraventricular premature complex, and wide QRS complex) had comparable predictive power (C‐statistic, 0.777 [95% CI, 0.766–0.788]). The simplified model showed a similar or better predictive performance than the previous models. In the subgroup analysis, the models performed relatively better in patients without risk factors. Specifically, the predictive power was lower in patients with heart failure or decreased renal function. Conclusions Although the 3‐year AF prediction model using both clinical and ECG variables showed the highest performance, the simplified model using age, sex, and 5 ECG diagnoses also had a comparable prediction power with broad applicability for incident AF.
{"title":"Development and Validation of 3‐Year Atrial Fibrillation Prediction Models Using Electronic Health Record With or Without Standardized Electrocardiogram Diagnosis and a Performance Comparison Among Models","authors":"Yunjin Yum, S. Shin, Hakje Yoo, Yong Hyun Kim, Eung Ju Kim, G. Lip, H. J. Joo","doi":"10.1161/JAHA.121.024045","DOIUrl":"https://doi.org/10.1161/JAHA.121.024045","url":null,"abstract":"Background Improved prediction of atrial fibrillation (AF) may allow for earlier interventions for stroke prevention, as well as mortality and morbidity from other AF‐related complications. We developed a clinically feasible and accurate AF prediction model using electronic health records and computerized ECG interpretation. Methods and Results A total of 671 318 patients were screened from 3 tertiary hospitals. After careful exclusion of cases with missing values and a prior AF diagnosis, AF prediction models were developed from the derivation cohort of 25 584 patients without AF at baseline. In the internal/external validation cohort of 117 523 patients, the model using 6 clinical features and 5 ECG diagnoses showed the highest performance for 3‐year new‐onset AF prediction (C‐statistic, 0.796 [95% CI, 0.785–0.806]). A more simplified model using age, sex, and 5 ECG diagnoses (atrioventricular block, fusion beats, marked sinus arrhythmia, supraventricular premature complex, and wide QRS complex) had comparable predictive power (C‐statistic, 0.777 [95% CI, 0.766–0.788]). The simplified model showed a similar or better predictive performance than the previous models. In the subgroup analysis, the models performed relatively better in patients without risk factors. Specifically, the predictive power was lower in patients with heart failure or decreased renal function. Conclusions Although the 3‐year AF prediction model using both clinical and ECG variables showed the highest performance, the simplified model using age, sex, and 5 ECG diagnoses also had a comparable prediction power with broad applicability for incident AF.","PeriodicalId":17189,"journal":{"name":"Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2022-06-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"74865346","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}
Jessica Fernandez, F. A. Montiel Ishino, Faustine Williams, N. Slopen, Allana T. Forde
Background Hypertension and diabetes disproportionately affect older non‐Hispanic Black and Hispanic adults in the United States. Chronic stress may partially explain these disparities. This study identified underlying stress profiles of older US adults, analyzed stress profiles in relation to hypertension and diabetes, examined the distribution of stress profiles by race and ethnicity, and assessed patterns of change in latent classes of stress over time. Methods and Results Latent class analysis was conducted with a nationally representative sample of older US adults who completed 3 waves of the HRS (Health and Retirement Study) (ie, 2010 [n=6863], 2014 [n=4995], and 2018 [n=3089]). Latent classes of stress in 2010 (ie, stress profiles) were identified using 15 indicators of unmet needs within 5 categories (ie, physiological, safety/security, belonging, esteem, and self‐fulfillment). Hypertension and diabetes status were examined as outcomes of latent class membership at 3 time points, and race and ethnicity were examined in association with class membership, adjusting for sociodemographic covariates. Finally, a latent transition analysis examined the stability of latent class membership and racial and ethnic differences in the patterns of stress profiles experienced from 2010 to 2018. Five classes were identified: Generally Unmet Needs (13% of sample), Generally Met Needs (42% of sample), Unmet Self‐Efficacy/Goal Needs (12% of sample), Unmet Financial Needs (20% of sample), and Unmet Social Belonging Needs (13% of sample). Compared with the Generally Met Needs class, the Generally Unmet Needs class had higher odds of hypertension (odds ratio [OR], 1.80; [95% CI, 1.35–2.39]) and diabetes (OR, 1.94; [95% CI, 1.45–2.59]), and the Unmet Financial Needs class had higher odds of diabetes (OR, 1.50; [95% CI, 1.10–2.05]). Non‐Hispanic Black participants compared with non‐Hispanic White participants had higher odds of being members of the Generally Unmet Needs, Unmet Self‐Efficacy/Goal Needs, and Unmet Financial Needs classes (OR, 2.70; [95% CI, 1.59–4.58]; OR, 1.99; [95% CI, 1.15–3.43]; and OR, 4.74; [95% CI, 3.32–6.76], respectively). Class membership remained relatively stable over time, with 93% of participants remaining in Generally Met Needs and 78% of participants remaining in Generally Unmet Needs across time points. Compared with non‐Hispanic White participants, non‐Hispanic Black participants had lower odds of Generally Met Needs class membership at any time point (OR, 0.60; [95% CI, 0.42–0.84]) and had lower odds of moving into the Generally Met Needs class and higher odds of moving into the Unmet Financial Needs class from 2010 to 2014 (OR, 0.33; [95% CI, 0.13–0.86]; and OR, 3.02; [95% CI, 1.16–7.87], respectively). Conclusions Underlying classes of stress based on unmet needs were associated with hypertension and diabetes status. Racial and ethnic differences were observed for both latent class membership and transitions between classes ov
{"title":"Hypertension and Diabetes Status by Patterns of Stress in Older Adults From the US Health and Retirement Study: A Latent Class Analysis","authors":"Jessica Fernandez, F. A. Montiel Ishino, Faustine Williams, N. Slopen, Allana T. Forde","doi":"10.1161/JAHA.121.024594","DOIUrl":"https://doi.org/10.1161/JAHA.121.024594","url":null,"abstract":"Background Hypertension and diabetes disproportionately affect older non‐Hispanic Black and Hispanic adults in the United States. Chronic stress may partially explain these disparities. This study identified underlying stress profiles of older US adults, analyzed stress profiles in relation to hypertension and diabetes, examined the distribution of stress profiles by race and ethnicity, and assessed patterns of change in latent classes of stress over time. Methods and Results Latent class analysis was conducted with a nationally representative sample of older US adults who completed 3 waves of the HRS (Health and Retirement Study) (ie, 2010 [n=6863], 2014 [n=4995], and 2018 [n=3089]). Latent classes of stress in 2010 (ie, stress profiles) were identified using 15 indicators of unmet needs within 5 categories (ie, physiological, safety/security, belonging, esteem, and self‐fulfillment). Hypertension and diabetes status were examined as outcomes of latent class membership at 3 time points, and race and ethnicity were examined in association with class membership, adjusting for sociodemographic covariates. Finally, a latent transition analysis examined the stability of latent class membership and racial and ethnic differences in the patterns of stress profiles experienced from 2010 to 2018. Five classes were identified: Generally Unmet Needs (13% of sample), Generally Met Needs (42% of sample), Unmet Self‐Efficacy/Goal Needs (12% of sample), Unmet Financial Needs (20% of sample), and Unmet Social Belonging Needs (13% of sample). Compared with the Generally Met Needs class, the Generally Unmet Needs class had higher odds of hypertension (odds ratio [OR], 1.80; [95% CI, 1.35–2.39]) and diabetes (OR, 1.94; [95% CI, 1.45–2.59]), and the Unmet Financial Needs class had higher odds of diabetes (OR, 1.50; [95% CI, 1.10–2.05]). Non‐Hispanic Black participants compared with non‐Hispanic White participants had higher odds of being members of the Generally Unmet Needs, Unmet Self‐Efficacy/Goal Needs, and Unmet Financial Needs classes (OR, 2.70; [95% CI, 1.59–4.58]; OR, 1.99; [95% CI, 1.15–3.43]; and OR, 4.74; [95% CI, 3.32–6.76], respectively). Class membership remained relatively stable over time, with 93% of participants remaining in Generally Met Needs and 78% of participants remaining in Generally Unmet Needs across time points. Compared with non‐Hispanic White participants, non‐Hispanic Black participants had lower odds of Generally Met Needs class membership at any time point (OR, 0.60; [95% CI, 0.42–0.84]) and had lower odds of moving into the Generally Met Needs class and higher odds of moving into the Unmet Financial Needs class from 2010 to 2014 (OR, 0.33; [95% CI, 0.13–0.86]; and OR, 3.02; [95% CI, 1.16–7.87], respectively). Conclusions Underlying classes of stress based on unmet needs were associated with hypertension and diabetes status. Racial and ethnic differences were observed for both latent class membership and transitions between classes ov","PeriodicalId":17189,"journal":{"name":"Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2022-06-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"74121496","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}
Michael Hauke, Robert Eckenstaler, A. Ripperger, Anna Ender, Heike Braun, R. Benndorf
Background The small GTPase RhoA (Ras homolog gene family, member A) regulates a variety of cellular processes, including cell motility, proliferation, survival, and permeability. In addition, there are reports indicating that RhoA‐ROCK (rho associated coiled‐coil containing protein kinase) activation is essential for VEGF (vascular endothelial growth factor)‐mediated angiogenesis, whereas other work suggests VEGF‐antagonistic effects of the RhoA‐ROCK axis. Methods and Results To elucidate this issue, we examined human umbilical vein endothelial cells and human coronary artery endothelial cells after stable overexpression (lentiviral transduction) of constitutively active (G14V/Q63L), dominant‐negative (T19N), or wild‐type RhoA using a series of in vitro angiogenesis assays (proliferation, migration, tube formation, angiogenic sprouting, endothelial cell viability) and a human umbilical vein endothelial cells xenograft assay in immune‐incompetent NOD scid gamma mice in vivo. Here, we report that expression of active and wild‐type RhoA but not dominant‐negative RhoA significantly inhibited endothelial cell proliferation, migration, tube formation, and angiogenic sprouting in vitro. Moreover, active RhoA increased endothelial cell death in vitro and decreased human umbilical vein endothelial cell‐related angiogenesis in vivo. Inhibition of RhoA by C3 transferase antagonized the inhibitory effects of RhoA and strongly enhanced VEGF‐induced angiogenic sprouting in control‐treated cells. In contrast, inhibition of RhoA effectors ROCK1/2 and LIMK1/2 (LIM domain kinase 1/2) did not significantly affect RhoA‐related effects, but increased angiogenic sprouting and migration of control‐treated cells. In agreement with these data, VEGF did not activate RhoA in human umbilical vein endothelial cells as measured by a Förster resonance energy transfer–based biosensor. Furthermore, global transcriptome and subsequent bioinformatic gene ontology enrichment analyses revealed that constitutively active RhoA induced a differentially expressed gene pattern that was enriched for gene ontology biological process terms associated with mitotic nuclear division, cell proliferation, cell motility, and cell adhesion, which included a significant decrease in VEGFR‐2 (vascular endothelial growth factor receptor 2) and NOS3 (nitric oxide synthase 3) expression. Conclusions Our data demonstrate that increased RhoA activity has the potential to trigger endothelial dysfunction and antiangiogenic effects independently of its well‐characterized downstream effectors ROCK and LIMK.
{"title":"Active RhoA Exerts an Inhibitory Effect on the Homeostasis and Angiogenic Capacity of Human Endothelial Cells","authors":"Michael Hauke, Robert Eckenstaler, A. Ripperger, Anna Ender, Heike Braun, R. Benndorf","doi":"10.1161/JAHA.121.025119","DOIUrl":"https://doi.org/10.1161/JAHA.121.025119","url":null,"abstract":"Background The small GTPase RhoA (Ras homolog gene family, member A) regulates a variety of cellular processes, including cell motility, proliferation, survival, and permeability. In addition, there are reports indicating that RhoA‐ROCK (rho associated coiled‐coil containing protein kinase) activation is essential for VEGF (vascular endothelial growth factor)‐mediated angiogenesis, whereas other work suggests VEGF‐antagonistic effects of the RhoA‐ROCK axis. Methods and Results To elucidate this issue, we examined human umbilical vein endothelial cells and human coronary artery endothelial cells after stable overexpression (lentiviral transduction) of constitutively active (G14V/Q63L), dominant‐negative (T19N), or wild‐type RhoA using a series of in vitro angiogenesis assays (proliferation, migration, tube formation, angiogenic sprouting, endothelial cell viability) and a human umbilical vein endothelial cells xenograft assay in immune‐incompetent NOD scid gamma mice in vivo. Here, we report that expression of active and wild‐type RhoA but not dominant‐negative RhoA significantly inhibited endothelial cell proliferation, migration, tube formation, and angiogenic sprouting in vitro. Moreover, active RhoA increased endothelial cell death in vitro and decreased human umbilical vein endothelial cell‐related angiogenesis in vivo. Inhibition of RhoA by C3 transferase antagonized the inhibitory effects of RhoA and strongly enhanced VEGF‐induced angiogenic sprouting in control‐treated cells. In contrast, inhibition of RhoA effectors ROCK1/2 and LIMK1/2 (LIM domain kinase 1/2) did not significantly affect RhoA‐related effects, but increased angiogenic sprouting and migration of control‐treated cells. In agreement with these data, VEGF did not activate RhoA in human umbilical vein endothelial cells as measured by a Förster resonance energy transfer–based biosensor. Furthermore, global transcriptome and subsequent bioinformatic gene ontology enrichment analyses revealed that constitutively active RhoA induced a differentially expressed gene pattern that was enriched for gene ontology biological process terms associated with mitotic nuclear division, cell proliferation, cell motility, and cell adhesion, which included a significant decrease in VEGFR‐2 (vascular endothelial growth factor receptor 2) and NOS3 (nitric oxide synthase 3) expression. Conclusions Our data demonstrate that increased RhoA activity has the potential to trigger endothelial dysfunction and antiangiogenic effects independently of its well‐characterized downstream effectors ROCK and LIMK.","PeriodicalId":17189,"journal":{"name":"Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2022-06-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"80458402","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. Madan, J. Abbott, R. Lennon, D. So, Andrea M MacDougall, M. McLaughlin, V. Murthy, J. Saw, C. Rihal, M. Farkouh, N. Pereira, S. Goodman
Background TAILOR‐PCI (Tailored Antiplatelet Initiation to Lessen Outcomes due to decreased Clopidogrel Response After Percutaneous Coronary Intervention) studied genotype‐guided selection of antiplatelet therapy after percutaneous coronary intervention versus conventional therapy with clopidogrel. The presence of CYP2C19 loss‐of‐function alleles in patients treated with clopidogrel may be associated with increased risk for ischemic events. We report a prespecified sex‐specific analysis of genotyping and associated cardiovascular outcomes from this study. Methods and Results Associations between sex and major adverse cardiac events (MACE: cardiovascular death, myocardial infarction, stroke, stent thrombosis, and severe recurrent ischemia) and Bleeding Academic Research Consortium (BARC) bleeding at 12 months were analyzed using Cox proportional‐hazards models. Among 5276 randomized patients, loss‐of‐function carriers were observed in ≈36% of both sexes, and >80% of carriers were heterozygotes. At 12 months, after adjustment for baseline differences, risks of MACE (HR , 1.28 [0.97 to 1.68]; P=0.088) and BARC bleeding (hazard ratio [HR], 1.36 [0.91 to 2.05]; P=0.14) were comparable among women and men. There were no significant interactions between sex and treatment strategy for MACE interaction P value (Pint =0.59) or BARC bleeding (P int=0.47) nor for sex and genotype (MACE P int=0.15, and BARC bleeding P int=0.60). Conclusions CYP2C19 loss‐of‐function alleles were present in ≈1 in 3 women and men. Women had similar adjusted risks of MACE and bleeding as men following percutaneous coronary intervention. Genotype‐guided therapy did not significantly reduce the risk of MACE or bleeding relative to conventional therapy for both sexes. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT01742117.
{"title":"Sex‐Specific Differences in Clinical Outcomes After Percutaneous Coronary Intervention: Insights from the TAILOR‐PCI Trial","authors":"M. Madan, J. Abbott, R. Lennon, D. So, Andrea M MacDougall, M. McLaughlin, V. Murthy, J. Saw, C. Rihal, M. Farkouh, N. Pereira, S. Goodman","doi":"10.1161/JAHA.121.024709","DOIUrl":"https://doi.org/10.1161/JAHA.121.024709","url":null,"abstract":"Background TAILOR‐PCI (Tailored Antiplatelet Initiation to Lessen Outcomes due to decreased Clopidogrel Response After Percutaneous Coronary Intervention) studied genotype‐guided selection of antiplatelet therapy after percutaneous coronary intervention versus conventional therapy with clopidogrel. The presence of CYP2C19 loss‐of‐function alleles in patients treated with clopidogrel may be associated with increased risk for ischemic events. We report a prespecified sex‐specific analysis of genotyping and associated cardiovascular outcomes from this study. Methods and Results Associations between sex and major adverse cardiac events (MACE: cardiovascular death, myocardial infarction, stroke, stent thrombosis, and severe recurrent ischemia) and Bleeding Academic Research Consortium (BARC) bleeding at 12 months were analyzed using Cox proportional‐hazards models. Among 5276 randomized patients, loss‐of‐function carriers were observed in ≈36% of both sexes, and >80% of carriers were heterozygotes. At 12 months, after adjustment for baseline differences, risks of MACE (HR , 1.28 [0.97 to 1.68]; P=0.088) and BARC bleeding (hazard ratio [HR], 1.36 [0.91 to 2.05]; P=0.14) were comparable among women and men. There were no significant interactions between sex and treatment strategy for MACE interaction P value (Pint =0.59) or BARC bleeding (P int=0.47) nor for sex and genotype (MACE P int=0.15, and BARC bleeding P int=0.60). Conclusions CYP2C19 loss‐of‐function alleles were present in ≈1 in 3 women and men. Women had similar adjusted risks of MACE and bleeding as men following percutaneous coronary intervention. Genotype‐guided therapy did not significantly reduce the risk of MACE or bleeding relative to conventional therapy for both sexes. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT01742117.","PeriodicalId":17189,"journal":{"name":"Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2022-06-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"84847529","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}
F. Moroni, L. Azzalini, L. Søndergaard, G. Attizzani, S. García, H. Jneid, M. Mamas, R. Bagur
Background There is a concern that resheathing/repositioning of transcatheter heart valves during transcatheter aortic valve implantation (TAVI) may lead to an increased risk of periprocedural complications. We aimed to evaluate the short‐ and long‐term impact on clinical outcomes of resheathing for repositioning of transcatheter heart valves during TAVI procedures. Methods and Results We conducted a systematic search of Embase, MEDLINE, and Cochrane Central Register of Controlled Trials databases to identify studies comparing outcomes between patients requiring resheathing/repositioning during TAVI and those who did not. Random‐effects meta‐analyses were used to estimate the association of resheathing compared with no resheathing with clinical outcomes after TAVI. Seven studies including 4501 participants (pooled mean age, 80.9±7.4 years; 54% women; and 1374 [30.5%] patients requiring resheathing/repositioning) were included in this study. No significant differences between the 2 groups were identified with regards to safety: 30‐day mortality (n=3125; odds ratio [OR], 0.74 [95% confidence interval [CI], 0.41–1.33]; I 2=0%), stroke (n=4121; OR, 1.09 [95% CI, 0.74–1.62]; I 2=0%), coronary obstruction (n=3000; OR, 2.35 [95% CI, 0.17–33.47]; I 2=75%), major vascular complications (n=3125; OR, 0.92 [95% CI, 0.66–1.33]; I 2=0%), major bleeding (n=3125; OR, 1.13 [95% CI, 0.94–2.01]; I 2=39%), acute kidney injury (n=3495; OR, 1.30 [95% CI, 0.64–2.62]; I 2=44%), and efficacy outcomes: device success (n=1196; OR, 0.77 [95% CI, 0.51–1.14]; I 2=0%), need for a second valve (n=3170; OR, 2.86 [95% CI, 0.96–8.48]; I 2=62%), significant (moderate or higher) paravalvular leak (n=1151; OR, 1.53 [95% CI, 0.83–2.80]; I 2=0%), and permanent pacemaker implantation (n=1908; OR, 1.04 [95% CI, 0.68–1.57]; I 2=58%). One‐year mortality was similar between groups (n=1972; OR, 1.00 [95% CI, 0.68–1.47]; I 2=0%). Conclusions Resheathing of transcatheter heart valves during TAVI is associated with similar periprocedural risk compared with no resheathing in several patient‐important outcomes. These data support the safety of current self‐expanding transcatheter heart valves with resheathing features. Registration URL: https://www.crd.york.ac.uk/prospero/; Unique identifier: CRD42021273715.
{"title":"Transcatheter Aortic Valve Implantation With and Without Resheathing and Repositioning: A Systematic Review and Meta‐analysis","authors":"F. Moroni, L. Azzalini, L. Søndergaard, G. Attizzani, S. García, H. Jneid, M. Mamas, R. Bagur","doi":"10.1161/JAHA.121.024707","DOIUrl":"https://doi.org/10.1161/JAHA.121.024707","url":null,"abstract":"Background There is a concern that resheathing/repositioning of transcatheter heart valves during transcatheter aortic valve implantation (TAVI) may lead to an increased risk of periprocedural complications. We aimed to evaluate the short‐ and long‐term impact on clinical outcomes of resheathing for repositioning of transcatheter heart valves during TAVI procedures. Methods and Results We conducted a systematic search of Embase, MEDLINE, and Cochrane Central Register of Controlled Trials databases to identify studies comparing outcomes between patients requiring resheathing/repositioning during TAVI and those who did not. Random‐effects meta‐analyses were used to estimate the association of resheathing compared with no resheathing with clinical outcomes after TAVI. Seven studies including 4501 participants (pooled mean age, 80.9±7.4 years; 54% women; and 1374 [30.5%] patients requiring resheathing/repositioning) were included in this study. No significant differences between the 2 groups were identified with regards to safety: 30‐day mortality (n=3125; odds ratio [OR], 0.74 [95% confidence interval [CI], 0.41–1.33]; I 2=0%), stroke (n=4121; OR, 1.09 [95% CI, 0.74–1.62]; I 2=0%), coronary obstruction (n=3000; OR, 2.35 [95% CI, 0.17–33.47]; I 2=75%), major vascular complications (n=3125; OR, 0.92 [95% CI, 0.66–1.33]; I 2=0%), major bleeding (n=3125; OR, 1.13 [95% CI, 0.94–2.01]; I 2=39%), acute kidney injury (n=3495; OR, 1.30 [95% CI, 0.64–2.62]; I 2=44%), and efficacy outcomes: device success (n=1196; OR, 0.77 [95% CI, 0.51–1.14]; I 2=0%), need for a second valve (n=3170; OR, 2.86 [95% CI, 0.96–8.48]; I 2=62%), significant (moderate or higher) paravalvular leak (n=1151; OR, 1.53 [95% CI, 0.83–2.80]; I 2=0%), and permanent pacemaker implantation (n=1908; OR, 1.04 [95% CI, 0.68–1.57]; I 2=58%). One‐year mortality was similar between groups (n=1972; OR, 1.00 [95% CI, 0.68–1.47]; I 2=0%). Conclusions Resheathing of transcatheter heart valves during TAVI is associated with similar periprocedural risk compared with no resheathing in several patient‐important outcomes. These data support the safety of current self‐expanding transcatheter heart valves with resheathing features. Registration URL: https://www.crd.york.ac.uk/prospero/; Unique identifier: CRD42021273715.","PeriodicalId":17189,"journal":{"name":"Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2022-06-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"87440705","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}
Monique M. Gardner, G. Keim, J. Hsia, A. Mai, J. William Gaynor, Andrew C. Glatz, N. Yehya
Background Neonates with heart disease requiring cardiopulmonary bypass surgery are at high risk for mortality and morbidity. As it is rare, short‐term mortality is difficult to use as a primary outcome for clinical studies. We proposed “ICU‐30” as a binary composite “poor” outcome consisting of: (1) mortality within 30 days, (2) intensive care unit (ICU) admission ≥30 days, or (3) ICU readmission before day 30. To measure the utility of this composite, we assessed its prognostic properties for 6‐ and 12‐month mortality. Methods and Results This was a retrospective single‐center cohort study of neonates requiring cardiopulmonary bypass between 2013 and 2020. Mortality among patients with and without the ICU‐30 outcome was compared using log‐rank tests and Cox regression. Areas under the receiver operating characteristic curves assessed the ability of the composite to predict 12‐month mortality. In 887 neonates, 232 (26.2%) experienced the ICU‐30 outcome, with more prolonged ICU stays and readmissions (both ≥9%) than 30‐day mortality (4.2%). ICU‐30 was associated with higher rates of 6‐ and 12‐month mortality (log‐rank P<0.001) and predicted 12‐month mortality with area under the receiver operating characteristic of 0.81 (95% CI, 0.77–0.85). In 30‐day survivors, both prolonged ICU stay (hazard ratio, 12.3; 95% CI, 6.70–22.7; P<0.001) and ICU readmission (hazard ratio, 2.99; 95% CI, 1.17–7.63; P=0.02) were associated with 12‐month mortality. Conclusions ICU‐30, a composite outcome of mortality, ICU length of stay, or ICU readmission by 30 days was associated with 6‐ and 12‐month mortality in neonates requiring cardiopulmonary bypass. ICU‐30 is captured in routine data collection and appears to be a valid binary patient‐centered outcome.
{"title":"Characterization of “ICU‐30”: A Binary Composite Outcome for Neonates With Critical Congenital Heart Disease","authors":"Monique M. Gardner, G. Keim, J. Hsia, A. Mai, J. William Gaynor, Andrew C. Glatz, N. Yehya","doi":"10.1161/JAHA.122.025494","DOIUrl":"https://doi.org/10.1161/JAHA.122.025494","url":null,"abstract":"Background Neonates with heart disease requiring cardiopulmonary bypass surgery are at high risk for mortality and morbidity. As it is rare, short‐term mortality is difficult to use as a primary outcome for clinical studies. We proposed “ICU‐30” as a binary composite “poor” outcome consisting of: (1) mortality within 30 days, (2) intensive care unit (ICU) admission ≥30 days, or (3) ICU readmission before day 30. To measure the utility of this composite, we assessed its prognostic properties for 6‐ and 12‐month mortality. Methods and Results This was a retrospective single‐center cohort study of neonates requiring cardiopulmonary bypass between 2013 and 2020. Mortality among patients with and without the ICU‐30 outcome was compared using log‐rank tests and Cox regression. Areas under the receiver operating characteristic curves assessed the ability of the composite to predict 12‐month mortality. In 887 neonates, 232 (26.2%) experienced the ICU‐30 outcome, with more prolonged ICU stays and readmissions (both ≥9%) than 30‐day mortality (4.2%). ICU‐30 was associated with higher rates of 6‐ and 12‐month mortality (log‐rank P<0.001) and predicted 12‐month mortality with area under the receiver operating characteristic of 0.81 (95% CI, 0.77–0.85). In 30‐day survivors, both prolonged ICU stay (hazard ratio, 12.3; 95% CI, 6.70–22.7; P<0.001) and ICU readmission (hazard ratio, 2.99; 95% CI, 1.17–7.63; P=0.02) were associated with 12‐month mortality. Conclusions ICU‐30, a composite outcome of mortality, ICU length of stay, or ICU readmission by 30 days was associated with 6‐ and 12‐month mortality in neonates requiring cardiopulmonary bypass. ICU‐30 is captured in routine data collection and appears to be a valid binary patient‐centered outcome.","PeriodicalId":17189,"journal":{"name":"Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2022-06-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"85391835","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}
Jun Wan, Shao-bin Lin, Zhuli Yu, Z. Song, Xuefeng Lin, Rongning Xu, Songlin Du
Background Extracellular vesicles (EVs) are a popular treatment candidate for myocardial injury. This work investigated the effects of mesenchymal stem cells (MSCs)–secreted EVs–derived miR‐200b‐3p on cardiomyocyte apoptosis and inflammatory response after myocardial infarction (MI) through targeting BCL2L11 (Bcl‐2–like protein 11) . Methods and Results EVs from MSCs were isolated and identified. EVs from MSCs with transfection of miR‐200b‐3p for overexpression were injected into MI mice. The effect of miR‐200b‐3p on cardiac function, infarction area, myocardial fibrosis, cardiomyocyte apoptosis, and inflammatory response was determined in MI mice. The targeting relationship between miR‐200b‐3p and BCL2L11 was verified, and the interaction between BCL2L11 and NLR family pyrin domain containing 1 (NLRP1) was also verified. MI mice were injected with an overexpressing BCL2L11 lentiviral vector to clarify whether BCL2L11 can regulate the effect of miR‐200b‐3p on MI mice. EVs from MSCs were successfully extracted. MSCs‐EVs improved cardiac function and reduced infarction area, apoptosis of cardiomyocytes, myocardial fibrosis, and inflammation in MI mice. Upregulation of miR‐200b‐3p further enhanced the effects of MSCs‐EVs on the myocardial injury of MI mice. BCL2L11 was targeted by miR‐200b‐3p and bound to NLRP1. Upregulation of BCL2L11 negated the role of miR‐200b‐3p–modified MSCs‐EVs in MI mice. Conclusions A summary was obtained that miR‐200b‐3p–encapsulated MSCs‐EVs protect against MI‐induced apoptosis of cardiomyocytes and inflammation via suppressing BCL2L11.
{"title":"Protective Effects of MicroRNA‐200b‐3p Encapsulated by Mesenchymal Stem Cells–Secreted Extracellular Vesicles in Myocardial Infarction Via Regulating BCL2L11","authors":"Jun Wan, Shao-bin Lin, Zhuli Yu, Z. Song, Xuefeng Lin, Rongning Xu, Songlin Du","doi":"10.1161/JAHA.121.024330","DOIUrl":"https://doi.org/10.1161/JAHA.121.024330","url":null,"abstract":"Background Extracellular vesicles (EVs) are a popular treatment candidate for myocardial injury. This work investigated the effects of mesenchymal stem cells (MSCs)–secreted EVs–derived miR‐200b‐3p on cardiomyocyte apoptosis and inflammatory response after myocardial infarction (MI) through targeting BCL2L11 (Bcl‐2–like protein 11) . Methods and Results EVs from MSCs were isolated and identified. EVs from MSCs with transfection of miR‐200b‐3p for overexpression were injected into MI mice. The effect of miR‐200b‐3p on cardiac function, infarction area, myocardial fibrosis, cardiomyocyte apoptosis, and inflammatory response was determined in MI mice. The targeting relationship between miR‐200b‐3p and BCL2L11 was verified, and the interaction between BCL2L11 and NLR family pyrin domain containing 1 (NLRP1) was also verified. MI mice were injected with an overexpressing BCL2L11 lentiviral vector to clarify whether BCL2L11 can regulate the effect of miR‐200b‐3p on MI mice. EVs from MSCs were successfully extracted. MSCs‐EVs improved cardiac function and reduced infarction area, apoptosis of cardiomyocytes, myocardial fibrosis, and inflammation in MI mice. Upregulation of miR‐200b‐3p further enhanced the effects of MSCs‐EVs on the myocardial injury of MI mice. BCL2L11 was targeted by miR‐200b‐3p and bound to NLRP1. Upregulation of BCL2L11 negated the role of miR‐200b‐3p–modified MSCs‐EVs in MI mice. Conclusions A summary was obtained that miR‐200b‐3p–encapsulated MSCs‐EVs protect against MI‐induced apoptosis of cardiomyocytes and inflammation via suppressing BCL2L11.","PeriodicalId":17189,"journal":{"name":"Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2022-06-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"79136178","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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