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":null,"pages":null},"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}
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":null,"pages":null},"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":null,"pages":null},"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":null,"pages":null},"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}
Pub Date : 2022-05-31DOI: 10.1101/2022.05.30.22275704
R. Tabassum, S. Ruotsalainen, L. Ottensmann, M. Gerl, C. Klose, T. Tukiainen, M. Pirinen, K. Simons, E. Widén, S. Ripatti
Despite well-recognized difference in the atherosclerotic cardiovascular disease (ASCVD) risk between men and women, sex differences in risk factors and sex specific mechanisms in the pathophysiology of ASCVD remain poorly understood. Lipid metabolism plays a central role in the development of ASCVD. Understanding sex differences in lipids and their genetic determinants could provide mechanistic insights into sex differences in ASCVD and aid in precise risk assessment. Thus, we examined sex differences in plasma levels of 179 lipid species from 7,266 participants and performed sex-stratified genome-wide association studies (GWAS) to evaluate contribution of genetic factors in sex differences. We sought for replication using independent data from 2,045 participants. Significant sex differences in levels of 141 lipid species were observed (P<7.0x10-4). Interestingly, 121 lipid species showed significant age-sex interactions with opposite age-related changes in 39 lipid species. In general, most of the cholesteryl esters, ceramides, lysophospholipids and glycerides were higher in 45-50-year-old men compared with women of same age, but the sex-differences narrowed down or reversed with age. We did not observe any major differences in genetic effect in the sex stratified GWAS which suggests that common genetic variants do not have a major role in sex differences in lipidome. In conclusion, our study provides a comprehensive view of sex differences in circulatory lipids pointing to potential sex differences in lipid metabolism, and highlights need for sex- and age-specific prevention strategies.
{"title":"Lipidome‐ and Genome‐Wide Study to Understand Sex Differences in Circulatory Lipids","authors":"R. Tabassum, S. Ruotsalainen, L. Ottensmann, M. Gerl, C. Klose, T. Tukiainen, M. Pirinen, K. Simons, E. Widén, S. Ripatti","doi":"10.1101/2022.05.30.22275704","DOIUrl":"https://doi.org/10.1101/2022.05.30.22275704","url":null,"abstract":"Despite well-recognized difference in the atherosclerotic cardiovascular disease (ASCVD) risk between men and women, sex differences in risk factors and sex specific mechanisms in the pathophysiology of ASCVD remain poorly understood. Lipid metabolism plays a central role in the development of ASCVD. Understanding sex differences in lipids and their genetic determinants could provide mechanistic insights into sex differences in ASCVD and aid in precise risk assessment. Thus, we examined sex differences in plasma levels of 179 lipid species from 7,266 participants and performed sex-stratified genome-wide association studies (GWAS) to evaluate contribution of genetic factors in sex differences. We sought for replication using independent data from 2,045 participants. Significant sex differences in levels of 141 lipid species were observed (P<7.0x10-4). Interestingly, 121 lipid species showed significant age-sex interactions with opposite age-related changes in 39 lipid species. In general, most of the cholesteryl esters, ceramides, lysophospholipids and glycerides were higher in 45-50-year-old men compared with women of same age, but the sex-differences narrowed down or reversed with age. We did not observe any major differences in genetic effect in the sex stratified GWAS which suggests that common genetic variants do not have a major role in sex differences in lipidome. In conclusion, our study provides a comprehensive view of sex differences in circulatory lipids pointing to potential sex differences in lipid metabolism, and highlights need for sex- and age-specific prevention strategies.","PeriodicalId":17189,"journal":{"name":"Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2022-05-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"85388967","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. Burzotta, F. Graziani, C. Trani, C. Aurigemma, P. Bruno, A. Lombardo, G. Liuzzo, M. Nesta, G. Lanza, E. Romagnoli, G. Locorotondo, A. Leone, N. Pavone, Claudio Spalletta, G. Pelargonio, T. Sanna, N. Aspromonte, F. Cavaliere, F. Crea, M. Massetti
Background A multidisciplinary approach might be pivotal for the management of patients with valvular heart disease (VHD), but clinical outcome data are lacking. Methods and Results At our institution, since 2014, internal guidelines recommended heart team consultations for patients with VHD. The clinical/echocardiographic characteristics, treatment recommendations, performed treatment, and early clinical outcomes of consecutive, hospitalized patients with VHD undergoing heart team evaluation were collected. Surgical risk was prospectively assessed by the EuroSCORE II and STS‐PROM. The primary end point of the study was early mortality. A total of 1004 patients with VHD with high clinical complexity (mean age, 75 years; mean EuroSCORE II, 9.4%; mean STS‐PROM, 5.6%; 48% ischemic heart disease; 29% chronic kidney disease, 9% oncologic/hematologic diseases) were enrolled. The heart team recommended an interventional treatment for 807 (80%) patients and conservative management for 197 (20%) patients. Management crossovers occurred in only 5% of patients. The recommended intervention was cardiac surgery for 230 (23%) patients, percutaneous treatment in 516 (51%) patients, and hybrid treatment in 61 (6%) patients. Early mortality occurred in 24 patients (2.4%) and was independently predicted by aortic stenosis, left ventricular ejection fraction, pulmonary artery systolic pressure, and conservative management recommendation. In patients referred to treatment, observed early mortality (1.7%) was significantly lower (P<0.001) than expected on the bases of both the STS‐PROM (5.2%) and EuroSCORE II (9.7%). Conclusions Within the limitations of its single‐center and observational design, the present study suggests that heart team–based management of patients with complex VHD is feasible and allows referral to a wide spectrum of interventions with promising early clinical results.
{"title":"Clinical Impact of Heart Team Decisions for Patients With Complex Valvular Heart Disease: A Large, Single‐Center Experience","authors":"F. Burzotta, F. Graziani, C. Trani, C. Aurigemma, P. Bruno, A. Lombardo, G. Liuzzo, M. Nesta, G. Lanza, E. Romagnoli, G. Locorotondo, A. Leone, N. Pavone, Claudio Spalletta, G. Pelargonio, T. Sanna, N. Aspromonte, F. Cavaliere, F. Crea, M. Massetti","doi":"10.1161/JAHA.121.024404","DOIUrl":"https://doi.org/10.1161/JAHA.121.024404","url":null,"abstract":"Background A multidisciplinary approach might be pivotal for the management of patients with valvular heart disease (VHD), but clinical outcome data are lacking. Methods and Results At our institution, since 2014, internal guidelines recommended heart team consultations for patients with VHD. The clinical/echocardiographic characteristics, treatment recommendations, performed treatment, and early clinical outcomes of consecutive, hospitalized patients with VHD undergoing heart team evaluation were collected. Surgical risk was prospectively assessed by the EuroSCORE II and STS‐PROM. The primary end point of the study was early mortality. A total of 1004 patients with VHD with high clinical complexity (mean age, 75 years; mean EuroSCORE II, 9.4%; mean STS‐PROM, 5.6%; 48% ischemic heart disease; 29% chronic kidney disease, 9% oncologic/hematologic diseases) were enrolled. The heart team recommended an interventional treatment for 807 (80%) patients and conservative management for 197 (20%) patients. Management crossovers occurred in only 5% of patients. The recommended intervention was cardiac surgery for 230 (23%) patients, percutaneous treatment in 516 (51%) patients, and hybrid treatment in 61 (6%) patients. Early mortality occurred in 24 patients (2.4%) and was independently predicted by aortic stenosis, left ventricular ejection fraction, pulmonary artery systolic pressure, and conservative management recommendation. In patients referred to treatment, observed early mortality (1.7%) was significantly lower (P<0.001) than expected on the bases of both the STS‐PROM (5.2%) and EuroSCORE II (9.7%). Conclusions Within the limitations of its single‐center and observational design, the present study suggests that heart team–based management of patients with complex VHD is feasible and allows referral to a wide spectrum of interventions with promising early clinical results.","PeriodicalId":17189,"journal":{"name":"Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2022-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"73690372","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}
Y. Hannawi, Dhananjay Vaidya, L. Yanek, Michelle C. Johansen, B. Kral, L. Becker, D. Becker, P. Nyquist
Background The periventricular white matter is more sensitive to the systemic hemodynamic alterations than the deep white matter because of differences in its vascular structure and systemic circulation relationship. We hypothesize that periventricular white matter hyperintensity (PVWMH) volume shows greater association than deep white matter hyperintensity (DWMH) volume with vascular properties (VPs) reflecting arterial stiffness and cardiovascular remodeling, indicators of the systemic circulation. Methods and Results A total of 426 participants (age, 59.0±6.1 years; 57.5% women; and 39.7% Black race) in the Genetic Study of Atherosclerosis Risk who were aged ≥50 years and had brain magnetic resonance imaging were studied. VPs included pulse pressure, hypertensive response to exercise, diastolic brachial artery diameter, diastolic common carotid artery diameter, common carotid artery distensibility coefficient, and left ventricular function. The relative associations of VPs with PVWMH and DWMH as multiple measures within the same individual were determined using multilevel linear models. We also determined if age modified the differences in VPs associations with PVWMH and DWMH. Our findings indicated that, within the same subject, PVWMH volume had greater association than DWMH volume with pulse pressure (P=0.002), hypertensive response to exercise (P=0.04), diastolic brachial artery diameter (P=0.012), and diastolic common carotid artery diameter (P=0.04), independent of age and cardiovascular risk factors. The differences of PVWMH versus DWMH associations with VPs did not differ at any age threshold. Conclusions We show, for the first time, that PVWMH has greater association than DWMH, independent of age, with vascular measurements of arterial stiffness and cardiovascular remodeling suggesting that changes in the systemic circulation affect the PVWMH and DWMH differently.
{"title":"Association of Vascular Properties With the Brain White Matter Hyperintensity in Middle‐Aged Population","authors":"Y. Hannawi, Dhananjay Vaidya, L. Yanek, Michelle C. Johansen, B. Kral, L. Becker, D. Becker, P. Nyquist","doi":"10.1161/JAHA.121.024606","DOIUrl":"https://doi.org/10.1161/JAHA.121.024606","url":null,"abstract":"Background The periventricular white matter is more sensitive to the systemic hemodynamic alterations than the deep white matter because of differences in its vascular structure and systemic circulation relationship. We hypothesize that periventricular white matter hyperintensity (PVWMH) volume shows greater association than deep white matter hyperintensity (DWMH) volume with vascular properties (VPs) reflecting arterial stiffness and cardiovascular remodeling, indicators of the systemic circulation. Methods and Results A total of 426 participants (age, 59.0±6.1 years; 57.5% women; and 39.7% Black race) in the Genetic Study of Atherosclerosis Risk who were aged ≥50 years and had brain magnetic resonance imaging were studied. VPs included pulse pressure, hypertensive response to exercise, diastolic brachial artery diameter, diastolic common carotid artery diameter, common carotid artery distensibility coefficient, and left ventricular function. The relative associations of VPs with PVWMH and DWMH as multiple measures within the same individual were determined using multilevel linear models. We also determined if age modified the differences in VPs associations with PVWMH and DWMH. Our findings indicated that, within the same subject, PVWMH volume had greater association than DWMH volume with pulse pressure (P=0.002), hypertensive response to exercise (P=0.04), diastolic brachial artery diameter (P=0.012), and diastolic common carotid artery diameter (P=0.04), independent of age and cardiovascular risk factors. The differences of PVWMH versus DWMH associations with VPs did not differ at any age threshold. Conclusions We show, for the first time, that PVWMH has greater association than DWMH, independent of age, with vascular measurements of arterial stiffness and cardiovascular remodeling suggesting that changes in the systemic circulation affect the PVWMH and DWMH differently.","PeriodicalId":17189,"journal":{"name":"Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2022-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"80489883","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}
Hyoung Youn Lee, Y. Jung, N. Mamadjonov, K. Jeung, Min Chul Kim, K. Lim, Chang‐Yeop Jeon, Youngjeon Lee, Hyung-Joong Kim
Background Postischemic cerebral hypoperfusion has been indicated as an important contributing factor to secondary cerebral injury after cardiac arrest. We evaluated the effects of sodium nitroprusside administered via a subdural intracranial catheter on the microcirculation, oxygenation, and electrocortical activity of the cerebral cortex in the early postresuscitation period using a pig model of cardiac arrest. Methods and Results Twenty‐nine pigs were resuscitated with closed cardiopulmonary resuscitation after 14 minutes of untreated ventricular fibrillation. Thirty minutes after restoration of spontaneous circulation, 24 pigs randomly received either 4 mg of sodium nitroprusside (IT‐SNP group) or saline placebo (IT‐saline group) via subdural intracranial catheters and were observed for 5 hours. The same dose of sodium nitroprusside was administered intravenously in another 5 pigs. Compared with the IT‐saline group, the IT‐SNP group had larger areas under the curve for tissue oxygen tension and percent changes of arteriole diameter and number of perfused microvessels from baseline (all P<0.05) monitored on the cerebral cortex during the 5‐hour period, without severe hemodynamic instability. This group also showed faster recovery of electrocortical activity measured using amplitude‐integrated electroencephalography. Repeated‐measures analysis of variance revealed significant group–time interactions for these parameters. Intravenously administered sodium nitroprusside caused profound hypotension but did not appear to increase the cerebral parameters. Conclusions Sodium nitroprusside administered via a subdural intracranial catheter increased post–restoration of spontaneous circulation cerebral cortical microcirculation and oxygenation and hastened electrocortical activity recovery in a pig model of cardiac arrest. Further studies are required to determine its impact on the long‐term neurologic outcomes.
{"title":"Effects of Sodium Nitroprusside Administered Via a Subdural Intracranial Catheter on the Microcirculation, Oxygenation, and Electrocortical Activity of the Cerebral Cortex in a Pig Cardiac Arrest Model","authors":"Hyoung Youn Lee, Y. Jung, N. Mamadjonov, K. Jeung, Min Chul Kim, K. Lim, Chang‐Yeop Jeon, Youngjeon Lee, Hyung-Joong Kim","doi":"10.1161/JAHA.122.025400","DOIUrl":"https://doi.org/10.1161/JAHA.122.025400","url":null,"abstract":"Background Postischemic cerebral hypoperfusion has been indicated as an important contributing factor to secondary cerebral injury after cardiac arrest. We evaluated the effects of sodium nitroprusside administered via a subdural intracranial catheter on the microcirculation, oxygenation, and electrocortical activity of the cerebral cortex in the early postresuscitation period using a pig model of cardiac arrest. Methods and Results Twenty‐nine pigs were resuscitated with closed cardiopulmonary resuscitation after 14 minutes of untreated ventricular fibrillation. Thirty minutes after restoration of spontaneous circulation, 24 pigs randomly received either 4 mg of sodium nitroprusside (IT‐SNP group) or saline placebo (IT‐saline group) via subdural intracranial catheters and were observed for 5 hours. The same dose of sodium nitroprusside was administered intravenously in another 5 pigs. Compared with the IT‐saline group, the IT‐SNP group had larger areas under the curve for tissue oxygen tension and percent changes of arteriole diameter and number of perfused microvessels from baseline (all P<0.05) monitored on the cerebral cortex during the 5‐hour period, without severe hemodynamic instability. This group also showed faster recovery of electrocortical activity measured using amplitude‐integrated electroencephalography. Repeated‐measures analysis of variance revealed significant group–time interactions for these parameters. Intravenously administered sodium nitroprusside caused profound hypotension but did not appear to increase the cerebral parameters. Conclusions Sodium nitroprusside administered via a subdural intracranial catheter increased post–restoration of spontaneous circulation cerebral cortical microcirculation and oxygenation and hastened electrocortical activity recovery in a pig model of cardiac arrest. Further studies are required to determine its impact on the long‐term neurologic outcomes.","PeriodicalId":17189,"journal":{"name":"Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2022-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"79008212","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}
G. Corn, Marie Lund, M. Hlatky, J. Wohlfahrt, M. Melbye
Background Change in low‐density lipoprotein cholesterol (LDL‐C) level after statin initiation varies widely among individuals, and in part may be because of factors shared by family members. Methods and Results We used the Danish national registers to identify 89 006 individuals who initiated statins between 2008 and 2018 and had LDL‐C measured immediately before and after the start of treatment. Among these, we identified 5148 first‐degree relatives and 3198 spouses. We decomposed the variation in attained LDL‐C level after statin initiation by applying a mixed‐effect model with 5 variance components (inter‐family and inter‐individual variance in pre‐statin LDL‐C level, inter‐family and inter‐individual variance in statin response, and residual variance). Results were presented as a percentage of the total variance explained by the different variance components. We found that half of the variation in attained LDL‐C level after statin initiation consisted of variance in statin response, approximately one third of variance in pre‐statin LDL‐C level, and the remaining 10% to 15% of residual variance. While the inter‐individual variance in statin response accounted for almost half of the LDL‐C variation in both cohorts, the inter‐family variance in statin response accounted for 3.3% among first‐degree relatives and for 6.0% among spouses. Conclusions Individual factors account for most of the variation in LDL‐C level after statin initiation; factors affecting statin response common within spouses and first‐degree relatives account for a similar share of variation. These results suggest a modest influence of shared genetics and shared familial environment on statin response.
{"title":"Familial Resemblance in Low‐Density Lipoprotein Cholesterol Response to Statins in the Danish Population","authors":"G. Corn, Marie Lund, M. Hlatky, J. Wohlfahrt, M. Melbye","doi":"10.1161/JAHA.121.025465","DOIUrl":"https://doi.org/10.1161/JAHA.121.025465","url":null,"abstract":"Background Change in low‐density lipoprotein cholesterol (LDL‐C) level after statin initiation varies widely among individuals, and in part may be because of factors shared by family members. Methods and Results We used the Danish national registers to identify 89 006 individuals who initiated statins between 2008 and 2018 and had LDL‐C measured immediately before and after the start of treatment. Among these, we identified 5148 first‐degree relatives and 3198 spouses. We decomposed the variation in attained LDL‐C level after statin initiation by applying a mixed‐effect model with 5 variance components (inter‐family and inter‐individual variance in pre‐statin LDL‐C level, inter‐family and inter‐individual variance in statin response, and residual variance). Results were presented as a percentage of the total variance explained by the different variance components. We found that half of the variation in attained LDL‐C level after statin initiation consisted of variance in statin response, approximately one third of variance in pre‐statin LDL‐C level, and the remaining 10% to 15% of residual variance. While the inter‐individual variance in statin response accounted for almost half of the LDL‐C variation in both cohorts, the inter‐family variance in statin response accounted for 3.3% among first‐degree relatives and for 6.0% among spouses. Conclusions Individual factors account for most of the variation in LDL‐C level after statin initiation; factors affecting statin response common within spouses and first‐degree relatives account for a similar share of variation. These results suggest a modest influence of shared genetics and shared familial environment on statin response.","PeriodicalId":17189,"journal":{"name":"Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2022-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"72616783","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}
Background Despite successful recanalization, up to half of patients with acute ischemic stroke caused by large‐vessel occlusion treated with endovascular treatment (EVT) do not recover to functional independence. We aim to evaluate the role of cerebral circulation time (CCT) as outcome predictor after EVT. Methods and Results We retrospectively enrolled consecutive patients with acute ischemic stroke–large‐vessel occlusion undergoing EVT. Three categories of CCT based on digital subtraction angiography were studied: CCT of the stroke side, CCT of the healthy side), and change of CCT of the stroke side versus CCT of the healthy side. Dramatic clinical recovery was defined as a 24‐hour National Institutes of Health Stroke Scale score ≤2 or ≥8 points drop. A modified Rankin Scale score ≤2 at 3 months was considered a favorable outcome. Logistic regression analysis was performed to evaluate the prediction of CCT on prognosis. One hundred patients were enrolled, of which 38 (38.0%) experienced a dramatic clinical recovery and 43 (43.0%) achieved a favorable outcome. Logistic regression analysis found that shorter change of CCT of the stroke side versus CCT of the healthy side and CCT of the stroke side were independent positive prognostic factors for dramatic clinical recovery (odds ratio [OR], 0.189; P=0.033; OR, 0.581; P=0.035) and favorable outcomes (OR, 0.142; P=0.020; OR, 0.581; P=0.046) after adjustment for potential confounders. A model including the change of CCT of the stroke side versus CCT of the healthy side also had significantly higher area under the curve values compared with the baseline model in patients with dramatic clinical recovery (0.780 versus 0.742) or favorable outcome (0.759 versus 0.713). Conclusions To our knowledge, this is the first report that CCT based on digital subtraction angiography data exhibits an independent predictive performance for clinical outcome in patients with acute ischemic stroke–large‐vessel occlusion after EVT. Given that this readily available CCT can provide alternative perfusion information during EVT, a prospective, multicenter trial is warranted.
尽管血管再通成功，但在接受血管内治疗(EVT)的大血管闭塞引起的急性缺血性卒中患者中，有多达一半的患者不能恢复功能独立。我们的目的是评估脑循环时间(CCT)作为EVT后预后预测因子的作用。方法和结果我们回顾性地招募了连续的急性缺血性卒中大血管闭塞患者进行EVT。研究了基于数字减影血管造影的三种CCT:卒中侧CCT、健康侧CCT，以及卒中侧CCT与健康侧CCT的变化。显著的临床恢复被定义为24小时美国国立卫生研究院卒中量表评分下降≤2或≥8分。3个月时改良Rankin量表评分≤2分被认为是一个有利的结果。采用Logistic回归分析评估CCT对预后的预测。100例患者入组，其中38例(38.0%)临床恢复显著，43例(43.0%)预后良好。Logistic回归分析发现，卒中侧CCT较健康侧和卒中侧CCT变化较短是显著临床恢复的独立阳性预后因素(优势比[OR]， 0.189;P = 0.033;或者,0.581;P=0.035)和良好结局(OR, 0.142;P = 0.020;或者,0.581;P=0.046)，校正了潜在混杂因素。与基线模型相比，包含卒中侧CCT与健康侧CCT变化的模型在临床恢复显著(0.780 vs 0.742)或预后良好(0.759 vs 0.713)的患者曲线下面积值也显著更高。据我们所知，这是首次报道基于数字减影血管造影数据的CCT对EVT后急性缺血性卒中大血管闭塞患者的临床结果具有独立的预测作用。鉴于这种现成的CCT可以在EVT期间提供替代灌注信息，因此有必要进行前瞻性的多中心试验。
{"title":"Cerebral Circulation Time After Thrombectomy: A Potential Predictor of Outcome After Recanalization in Acute Stroke","authors":"Jia-Qi Wang, Ying-Jia Wang, Jingsong Qiu, Wei Li, Xian-Hui Sun, Yong-Gang Zhao, Xin Liu, Ziai Zhao, Liang Liu, Thanh N. Nguyen, Huisheng Chen","doi":"10.1161/JAHA.122.025853","DOIUrl":"https://doi.org/10.1161/JAHA.122.025853","url":null,"abstract":"Background Despite successful recanalization, up to half of patients with acute ischemic stroke caused by large‐vessel occlusion treated with endovascular treatment (EVT) do not recover to functional independence. We aim to evaluate the role of cerebral circulation time (CCT) as outcome predictor after EVT. Methods and Results We retrospectively enrolled consecutive patients with acute ischemic stroke–large‐vessel occlusion undergoing EVT. Three categories of CCT based on digital subtraction angiography were studied: CCT of the stroke side, CCT of the healthy side), and change of CCT of the stroke side versus CCT of the healthy side. Dramatic clinical recovery was defined as a 24‐hour National Institutes of Health Stroke Scale score ≤2 or ≥8 points drop. A modified Rankin Scale score ≤2 at 3 months was considered a favorable outcome. Logistic regression analysis was performed to evaluate the prediction of CCT on prognosis. One hundred patients were enrolled, of which 38 (38.0%) experienced a dramatic clinical recovery and 43 (43.0%) achieved a favorable outcome. Logistic regression analysis found that shorter change of CCT of the stroke side versus CCT of the healthy side and CCT of the stroke side were independent positive prognostic factors for dramatic clinical recovery (odds ratio [OR], 0.189; P=0.033; OR, 0.581; P=0.035) and favorable outcomes (OR, 0.142; P=0.020; OR, 0.581; P=0.046) after adjustment for potential confounders. A model including the change of CCT of the stroke side versus CCT of the healthy side also had significantly higher area under the curve values compared with the baseline model in patients with dramatic clinical recovery (0.780 versus 0.742) or favorable outcome (0.759 versus 0.713). Conclusions To our knowledge, this is the first report that CCT based on digital subtraction angiography data exhibits an independent predictive performance for clinical outcome in patients with acute ischemic stroke–large‐vessel occlusion after EVT. Given that this readily available CCT can provide alternative perfusion information during EVT, a prospective, multicenter trial is warranted.","PeriodicalId":17189,"journal":{"name":"Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2022-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"73828646","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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