Pub Date : 2024-09-18DOI: 10.1101/2024.09.17.24313849
Farman Ali, Shaaf Ahmad, Aman Ullah, Adarsh Raja, Faizan Ahmed, Prinka Perswani, Ahsan Alam, Jishanth Mattumpuram, Muhammad Talha Maniya, Hamza Janjua, Tyler J Bonkowski, Aravinda Nanjundappa
BACKGROUND: Although there is increasing emphasis on introducing palliative care for patients with Heart failure, it is not well characterized where adults with HF spend their final days before death. AIM: This study analyzed the locations and circumstances of death among adults with HF in the United States using data from the CDC-WONDER database. METHODS: The study examined mortality data of individuals aged ≥20 years, with HF listed as the underlying cause of death between 1999 and 2023. The place of death was categorized as the emergency room (ER), hospice/nursing home, inpatient medical facility, or home. Multivariable logistic regression was used to determine the relationship between death location and demographic factors. RESULTS: From 1999 to 2023, HF-related deaths decreased from 1999 (3.60% and 143.6 AAMR) to 2010 (3.47% and 123.1 AAMR). From 2010 onwards, a gradual rise is seen, with the rate of HF deaths reaching 5.18% and 168.1 AAMR in 2023. Notably, deaths at home increased from 18.41% (50,648 of 275,132) in 1999 to 33.47% (132,470 of 395,826) in 2023 and deaths in hospice/nursing homes increased from 30.95% (85,144 of 275,132) in 1999 to 34.71% (116,634 of 336,014) in 2017 and then sudden fall was observed until 2023 to 29.54% (116,931 of 395,826). Older adults (65+) were more likely to die in inpatient facilities. Gender, ethnicity, and urbanization influenced the place of death, with males, whites, and those residing in large metropolitan areas more likely to die in medical facilities. CONCLUSIONS: We highlight the changing patterns in the locations of death among HF patients, emphasizing the need for improved home and hospice care services. Addressing disparities in healthcare access and enhancing palliative care are essential for improving end-of-life experiences. Further research is needed to investigate the factors that contribute to these trends.
{"title":"Where Adults with Heart Failure Die: Insights from the CDC-WONDER Database","authors":"Farman Ali, Shaaf Ahmad, Aman Ullah, Adarsh Raja, Faizan Ahmed, Prinka Perswani, Ahsan Alam, Jishanth Mattumpuram, Muhammad Talha Maniya, Hamza Janjua, Tyler J Bonkowski, Aravinda Nanjundappa","doi":"10.1101/2024.09.17.24313849","DOIUrl":"https://doi.org/10.1101/2024.09.17.24313849","url":null,"abstract":"BACKGROUND: Although there is increasing emphasis on introducing palliative care for patients with Heart failure, it is not well characterized where adults with HF spend their final days before death. AIM: This study analyzed the locations and circumstances of death among adults with HF in the United States using data from the CDC-WONDER database.\u0000METHODS: The study examined mortality data of individuals aged ≥20 years, with HF listed as the underlying cause of death between 1999 and 2023. The place of death was categorized as the emergency room (ER), hospice/nursing home, inpatient medical facility, or home. Multivariable logistic regression was used to determine the relationship between death location and demographic factors.\u0000RESULTS: From 1999 to 2023, HF-related deaths decreased from 1999 (3.60% and 143.6 AAMR) to 2010 (3.47% and 123.1 AAMR). From 2010 onwards, a gradual rise is seen, with the rate of HF deaths reaching 5.18% and 168.1 AAMR in 2023. Notably, deaths at home increased from 18.41% (50,648 of 275,132) in 1999 to 33.47% (132,470 of 395,826) in 2023 and deaths in hospice/nursing homes increased from 30.95% (85,144 of 275,132) in 1999 to 34.71% (116,634 of 336,014) in 2017 and then sudden fall was observed until 2023 to 29.54% (116,931 of 395,826). Older adults (65+) were more likely to die in inpatient facilities. Gender, ethnicity, and urbanization influenced the place of death, with males, whites, and those residing in large metropolitan areas more likely to die in medical facilities.\u0000CONCLUSIONS: We highlight the changing patterns in the locations of death among HF patients, emphasizing the need for improved home and hospice care services. Addressing disparities in healthcare access and enhancing palliative care are essential for improving end-of-life experiences. Further research is needed to investigate the factors that contribute to these trends.","PeriodicalId":501297,"journal":{"name":"medRxiv - Cardiovascular Medicine","volume":"17 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142258548","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 : 2024-09-17DOI: 10.1101/2024.09.16.24313782
Kuan-Chih Huang, Ting-Tse Lin, Cho-Kai Wu, Lung-Chun Lin, Lian-Yu Lin
Background Symptoms of heart failure with preserved ejection fraction (HFpEF) are closely related to elevated pulmonary capillary wedge pressure (PCWP) during exercise. Understanding right ventricular (RV) myocardial work, using RV pressure–strain loops to assess RV function in HFpEF, is lacking. The study aims to evaluate the effectiveness of right ventricular myocardial work parameters in diagnosing HFpEF and their correlation with pulmonary capillary wedge pressure during exercise. Methods The study included patients who underwent invasive cardiopulmonary exercise tests, measuring pressures at rest and during exercise to identify HFpEF. Echocardiography assessed left and right ventricular parameters. RV myocardial work was calculated using strain-rate and pressure curves, matched with ECG data. RV global constructive work (RV GCW), RV global work index (RV GWI), RV global wasted work (RV GWW), and RV global work efficiency (RV GWE) were analyzed and compared with invasively measured PCWP at rest and peak exercise. Results Forty-one patients with adequate data were enrolled, with 21 diagnosed with HFpEF. No significant differences in various echocardiographic parameters were found between HFpEF and non-HFpEF groups, except higher post-exercise PCWP and mean pulmonary artery pressure in HFpEF patients. HFpEF patients had higher RV GWW and lower RV GWE. RV GWW and RV GWE had higher predictive ability for HFpEF diagnosis compared to other echocardiographic parameters. RV GCW (r = 0.504, P = 0.001) and RV GWW (r = 0.621, P < 0.001) correlated with post-exercise ΔPCWP and exercise PCWP, with RV GWW independently associated with both after adjustment for confounding factors. Conclusions RV GWW is a novel predictive parameter that provides a better explanation of RV performance regarding post-exercise ΔPCWP than other standard echocardiographic parameters in HFpEF.
{"title":"Right Ventricular Work and Pulmonary Capillary Wedge Pressure in Heart Failure with Preserved Ejection Fraction","authors":"Kuan-Chih Huang, Ting-Tse Lin, Cho-Kai Wu, Lung-Chun Lin, Lian-Yu Lin","doi":"10.1101/2024.09.16.24313782","DOIUrl":"https://doi.org/10.1101/2024.09.16.24313782","url":null,"abstract":"Background\u0000Symptoms of heart failure with preserved ejection fraction (HFpEF) are closely related to elevated pulmonary capillary wedge pressure (PCWP) during exercise. Understanding right ventricular (RV) myocardial work, using RV pressure–strain loops to assess RV function in HFpEF, is lacking. The study aims to evaluate the effectiveness of right ventricular myocardial work parameters in diagnosing HFpEF and their correlation with pulmonary capillary wedge pressure during exercise.\u0000Methods\u0000The study included patients who underwent invasive cardiopulmonary exercise tests, measuring pressures at rest and during exercise to identify HFpEF. Echocardiography assessed left and right ventricular parameters. RV myocardial work was calculated using strain-rate and pressure curves, matched with ECG data. RV global constructive work (RV GCW), RV global work index (RV GWI), RV global wasted work (RV GWW), and RV global work efficiency (RV GWE) were analyzed and compared with invasively measured PCWP at rest and peak exercise. Results\u0000Forty-one patients with adequate data were enrolled, with 21 diagnosed with HFpEF. No significant differences in various echocardiographic parameters were found between HFpEF and non-HFpEF groups, except higher post-exercise PCWP and mean pulmonary artery pressure in HFpEF patients. HFpEF patients had higher RV GWW and lower RV GWE. RV GWW and RV GWE had higher predictive ability for HFpEF diagnosis compared to other echocardiographic parameters. RV GCW (r = 0.504, P = 0.001) and RV GWW (r = 0.621, P < 0.001) correlated with post-exercise ΔPCWP and exercise PCWP, with RV GWW independently associated with both after adjustment for confounding factors.\u0000Conclusions\u0000RV GWW is a novel predictive parameter that provides a better explanation of RV performance regarding post-exercise ΔPCWP than other standard echocardiographic parameters in HFpEF.","PeriodicalId":501297,"journal":{"name":"medRxiv - Cardiovascular Medicine","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142258346","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 : 2024-09-17DOI: 10.1101/2024.09.16.24313783
Julia Gallucci, Justin Ng, Maria T. Secara, Brett D.M Jones, Colin Hawco, M. Omair Husain, Nusrat Husain, Imran B. Chaudhry, Aristotle N. Voineskos, Muhammad Ishrat Husain
Background: Depression is prevalent among patients with congestive heart failure (CHF) and is associated with increased mortality and healthcare utilization. However, most research has focused on high-income countries, leaving a gap in knowledge regarding the relationship between depression and CHF in low-to-middle-income countries (LMICs). This study aimed to delineate depressive symptom trajectories and identify potential risk factors for poor outcomes among CHF patients. Methods: Longitudinal data from 783 patients with CHF from public hospitals in Karachi, Pakistan was analyzed. Depressive symptom severity was assessed using the Beck Depression Inventory (BDI). Baseline and 6-month follow-up BDI scores were clustered through Gaussian Mixture Modeling to identify distinct depressive symptom subgroups and extract trajectory labels. Further, a random forest algorithm was utilized to determine baseline demographic, clinical, and behavioral predictors for each trajectory. Results: Four depressive symptom trajectories were identified: 'good prognosis,' 'remitting course,' 'clinical worsening,' and 'persistent course.' Risk factors associated with persistent depressive symptoms included lower quality of life and the New York Heart Association (NYHA) class 3 classification of CHF. Protective factors linked to a good prognosis included less disability and a non-NYHA class 3 classification of CHF. Conclusions: By identifying key characteristics of patients at heightened risk of depression, clinicians can be aware of risk factors and better identify patients who may need greater monitoring and appropriate follow-up care. Keywords: congestive heart failure, depressive symptom trajectories, low-to-middle-income countries, risk factors, protective factors, longitudinal study.
{"title":"A longitudinal study of depressive symptom trajectories and risk factors in congestive heart failure","authors":"Julia Gallucci, Justin Ng, Maria T. Secara, Brett D.M Jones, Colin Hawco, M. Omair Husain, Nusrat Husain, Imran B. Chaudhry, Aristotle N. Voineskos, Muhammad Ishrat Husain","doi":"10.1101/2024.09.16.24313783","DOIUrl":"https://doi.org/10.1101/2024.09.16.24313783","url":null,"abstract":"Background: Depression is prevalent among patients with congestive heart failure (CHF) and is associated with increased mortality and healthcare utilization. However, most research has focused on high-income countries, leaving a gap in knowledge regarding the relationship between depression and CHF in low-to-middle-income countries (LMICs). This study aimed to delineate depressive symptom trajectories and identify potential risk factors for poor outcomes among CHF patients. Methods: Longitudinal data from 783 patients with CHF from public hospitals in Karachi, Pakistan was analyzed. Depressive symptom severity was assessed using the Beck Depression Inventory (BDI). Baseline and 6-month follow-up BDI scores were clustered through Gaussian Mixture Modeling to identify distinct depressive symptom subgroups and extract trajectory labels. Further, a random forest algorithm was utilized to determine baseline demographic, clinical, and behavioral predictors for each trajectory. Results: Four depressive symptom trajectories were identified: 'good prognosis,' 'remitting course,' 'clinical worsening,' and 'persistent course.' Risk factors associated with persistent depressive symptoms included lower quality of life and the New York Heart Association (NYHA) class 3 classification of CHF. Protective factors linked to a good prognosis included less disability and a non-NYHA class 3 classification of CHF. Conclusions: By identifying key characteristics of patients at heightened risk of depression, clinicians can be aware of risk factors and better identify patients who may need greater monitoring and appropriate follow-up care. Keywords: congestive heart failure, depressive symptom trajectories, low-to-middle-income countries, risk factors, protective factors, longitudinal study.","PeriodicalId":501297,"journal":{"name":"medRxiv - Cardiovascular Medicine","volume":"20 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142258344","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}
Objectives: This study aimed to investigate the relationship between Life's Essential 8 (LE8) and the Atherogenic Index of Plasma (AIP). Methods: We conducted an analysis of data from 8,215 U.S. adults aged 20 years and older, utilizing the National Health and Nutrition Examination Survey data from 2007 to 2018. Based on LE8 scores, Cardiovascular Health (CVH) was stratified into three levels—low, moderate, and high—while AIP was categorized into four risk levels: extremely low (AIP<-0.3), low (-0.3≤AIP<0.1), medium (0.1≤AIP<0.24), and high (AIP≤0.24). Weighted ordinal logistic regression analysis was utilized to examine the association between CVH scores and AIP risk levels, adjusting for potential confounding variables. Results: A significant inverse correlation exists between CVH scores and AIP risk levels (OR=0.51, 95%CI: 0.49-0.54, P<0.001). Higher CVH scores were associated with lower AIP risk levels, while lower CVH scores corresponded to elevated AIP risk levels. Notably, improvements in specific CVH components such as Body Mass Index and Blood Lipids exhibited a strong relationship with reductions in AIP risk levels. Conclusions: Enhancing CVH is vital for effectively reducing AIP risk levels, thus underscoring the critical importance of health management strategies in the prevention of cardiovascular diseases.
{"title":"Association Between Life's Essential 8 and Atherogenic Index of Plasma in Adults: Insights from NHANES 2007-2018","authors":"Longhui Xu, Kai-wen Ding, Guo-dong Yang, Xiao-xuan Han, Xiao Cong, Rong-hui Wang, Xin-ru Liu, Na Li, Cui-ping Xu","doi":"10.1101/2024.09.16.24313778","DOIUrl":"https://doi.org/10.1101/2024.09.16.24313778","url":null,"abstract":"Objectives: This study aimed to investigate the relationship between Life's Essential 8 (LE8) and the Atherogenic Index of Plasma (AIP).\u0000Methods: We conducted an analysis of data from 8,215 U.S. adults aged 20 years and older, utilizing the National Health and Nutrition Examination Survey data from 2007 to 2018. Based on LE8 scores, Cardiovascular Health (CVH) was stratified into three levels—low, moderate, and high—while AIP was categorized into four risk levels: extremely low (AIP<-0.3), low (-0.3≤AIP<0.1), medium (0.1≤AIP<0.24), and high (AIP≤0.24). Weighted ordinal logistic regression analysis was utilized to examine the association between CVH scores and AIP risk levels, adjusting for potential confounding variables. Results: A significant inverse correlation exists between CVH scores and AIP risk levels (OR=0.51, 95%CI: 0.49-0.54, P<0.001). Higher CVH scores were associated with lower AIP risk levels, while lower CVH scores corresponded to elevated AIP risk levels. Notably, improvements in specific CVH components such as Body Mass Index and Blood Lipids exhibited a strong relationship with reductions in AIP risk levels. Conclusions: Enhancing CVH is vital for effectively reducing AIP risk levels, thus underscoring the critical importance of health management strategies in the prevention of cardiovascular diseases.","PeriodicalId":501297,"journal":{"name":"medRxiv - Cardiovascular Medicine","volume":"71 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142258549","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 : 2024-09-16DOI: 10.1101/2024.09.15.24313717
Iman Beheshti, odelia elkana
Background: Cognitive reserve, often approximated by levels of education, is thought to protect against the deleterious effects of brain pathology on cognitive function. White matter hyperintensities (WMHs) are commonly associated with aging and cognitive decline, and higher WMH burden has been linked to the progression from healthy cognitive status (HC) to mild cognitive impairment (MCI). Understanding how cognitive reserve, as indicated by education, influences the relationship between WMH burden and cognitive outcomes can provide valuable insights for interventions aimed at delaying cognitive decline. Objective: This study investigates the moderating role of education, as a proxy for cognitive reserve, on the relationship between WMH burden and the transition from HC to MCI. Methods: Data were obtained from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database, focusing on participants classified as cognitively healthy at baseline. A total of 153 cognitively healthy adults at the baseline were split into two groups: one group (n=85) remained cognitively healthy for at least 7 years, while the other group (n=68) progressed to MCI within 7 years. A multiple linear regression model was used to examine the interaction between group membership, baseline age, education, and sex in predicting WMH loads. The primary focus was on the interaction between group membership and education to assess the protective effect of cognitive reserve. Results: The regression model explained 18.5% of the variance in WMH load. The analysis revealed statistically significant interaction between group membership and education on WMH loads (Interaction term: β = -0.097, p = 0.047), indicating that higher education levels are associated with a reduced WMH burden among individuals who progressed to MCI. The main effect of education alone was not significant, nor were the interactions involving sex (p > 0.05). Conclusion: These findings support the hypothesis that education, as a proxy for cognitive reserve, provides a protective effect against the accumulation of WMH burden in older adults. The results suggest that higher cognitive reserve may mitigate the impact of neurodegenerative processes, thereby delaying the transition from HC to MCI. This underscores the importance of educational attainment in the preservation of cognitive health during aging.
{"title":"Education as a Proxy for Cognitive Reserve: Moderating Effects on White Matter Hyperintensity Burden in Healthy Aging and Cognitive Decline","authors":"Iman Beheshti, odelia elkana","doi":"10.1101/2024.09.15.24313717","DOIUrl":"https://doi.org/10.1101/2024.09.15.24313717","url":null,"abstract":"Background: Cognitive reserve, often approximated by levels of education, is thought to protect against the deleterious effects of brain pathology on cognitive function. White matter hyperintensities (WMHs) are commonly associated with aging and cognitive decline, and higher WMH burden has been linked to the progression from healthy cognitive status (HC) to mild cognitive impairment (MCI). Understanding how cognitive reserve, as indicated by education, influences the relationship between WMH burden and cognitive outcomes can provide valuable insights for interventions aimed at delaying cognitive decline. Objective: This study investigates the moderating role of education, as a proxy for cognitive reserve, on the relationship between WMH burden and the transition from HC to MCI. Methods: Data were obtained from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database, focusing on participants classified as cognitively healthy at baseline. A total of 153 cognitively healthy adults at the baseline were split into two groups: one group (n=85) remained cognitively healthy for at least 7 years, while the other group (n=68) progressed to MCI within 7 years. A multiple linear regression model was used to examine the interaction between group membership, baseline age, education, and sex in predicting WMH loads. The primary focus was on the interaction between group membership and education to assess the protective effect of cognitive reserve. Results: The regression model explained 18.5% of the variance in WMH load. The analysis revealed statistically significant interaction between group membership and education on WMH loads (Interaction term: β = -0.097, p = 0.047), indicating that higher education levels are associated with a reduced WMH burden among individuals who progressed to MCI. The main effect of education alone was not significant, nor were the interactions involving sex (p > 0.05). Conclusion:\u0000These findings support the hypothesis that education, as a proxy for cognitive reserve, provides a protective effect against the accumulation of WMH burden in older adults. The results suggest that higher cognitive reserve may mitigate the impact of neurodegenerative processes, thereby delaying the transition from HC to MCI. This underscores the importance of educational attainment in the preservation of cognitive health during aging.","PeriodicalId":501297,"journal":{"name":"medRxiv - Cardiovascular Medicine","volume":"32 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142258348","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 : 2024-09-16DOI: 10.1101/2024.09.15.24313706
Ayesha Imran Butt, Fazila Afzal, Sukaina Raza, FNU Namal, Dawood Ahmed, Hassaan Abid, Muhammad Hudaib, Zainab Safdar Ali Sarwar, Soha Bashir, Asadullah Khalid, Umer Hassan, Mohammad Ebad Ur Rehman, Huzaifa Ahmad Cheema, Ali Husnain, Usama Anwar, Muhammad Mohid Tahir, Adeel Ahmad, Wajeeh Ur Rehman, Raheel Ahmed
Abstract Background: Contrast-induced nephropathy (CIN) is a potentially serious complication of intravenous or intra-arterial contrast administration during angiographic procedures that results in renal dysfunction. This meta-analysis assesses the efficacy and safety of nicorandil for the prevention of CIN in patients undergoing percutaneous coronary intervention (PCI) or coronary angiography (CAG). Methods: Cochrane Central Register of Controlled Trials, MEDLINE, Embase, and ClinicalTrials.gov were used to perform a thorough literature search from their inception to July 2024. A random-effects meta-analysis was performed on RevMan and pooled estimates were presented as forest plots. The Mantel-Haenszel method was used for dichotomous outcomes and risk ratios (RRs) were calculated along with 95% confidence intervals (95% CI). Results: This meta-analysis included 12 RCTs consisting of 2787 participants (nicorandil: 1418, control: 1394). The use of nicorandil was protective against CIN (RR 0.38, 95% CI 0.29-0.50). The incidence of major adverse events was comparable in both groups (RR 0.77, 95% CI 0.52-1.13, p=0.18). Similarly, the use of nicorandil did not affect the risk of developing stroke (RR 1.05), myocardial infarction (RR 0.90), heart failure (RR 0.81), cardiac death (RR 0.90), and dialysis (RR 0.70). Conclusion: This study revealed that nicorandil effectively reduced the risk of developing CIN in patients undergoing angiographic procedures like PCI or coronary angiography. However, more RCTs should be conducted for a more definitive conclusion.
{"title":"Efficacy and Safety of Nicorandil for Prevention of Contrast-Induced Nephropathy in Patients Undergoing Coronary Procedures: A Systematic Review and Meta-Analysis","authors":"Ayesha Imran Butt, Fazila Afzal, Sukaina Raza, FNU Namal, Dawood Ahmed, Hassaan Abid, Muhammad Hudaib, Zainab Safdar Ali Sarwar, Soha Bashir, Asadullah Khalid, Umer Hassan, Mohammad Ebad Ur Rehman, Huzaifa Ahmad Cheema, Ali Husnain, Usama Anwar, Muhammad Mohid Tahir, Adeel Ahmad, Wajeeh Ur Rehman, Raheel Ahmed","doi":"10.1101/2024.09.15.24313706","DOIUrl":"https://doi.org/10.1101/2024.09.15.24313706","url":null,"abstract":"Abstract\u0000Background: Contrast-induced nephropathy (CIN) is a potentially serious complication of intravenous or intra-arterial contrast administration during angiographic procedures that results in renal dysfunction. This meta-analysis assesses the efficacy and safety of nicorandil for the prevention of CIN in patients undergoing percutaneous coronary intervention (PCI) or coronary angiography (CAG).\u0000Methods: Cochrane Central Register of Controlled Trials, MEDLINE, Embase, and ClinicalTrials.gov were used to perform a thorough literature search from their inception to July 2024. A random-effects meta-analysis was performed on RevMan and pooled estimates were presented as forest plots. The Mantel-Haenszel method was used for dichotomous outcomes and risk ratios (RRs) were calculated along with 95% confidence intervals (95% CI).\u0000Results: This meta-analysis included 12 RCTs consisting of 2787 participants (nicorandil: 1418, control: 1394). The use of nicorandil was protective against CIN (RR 0.38, 95% CI 0.29-0.50). The incidence of major adverse events was comparable in both groups (RR 0.77, 95% CI 0.52-1.13, p=0.18). Similarly, the use of nicorandil did not affect the risk of developing stroke (RR 1.05), myocardial infarction (RR 0.90), heart failure (RR 0.81), cardiac death (RR 0.90), and dialysis (RR 0.70).\u0000Conclusion: This study revealed that nicorandil effectively reduced the risk of developing CIN in patients undergoing angiographic procedures like PCI or coronary angiography. However, more RCTs should be conducted for a more definitive conclusion.","PeriodicalId":501297,"journal":{"name":"medRxiv - Cardiovascular Medicine","volume":"16 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142258347","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 : 2024-09-15DOI: 10.1101/2024.09.13.24313662
Abdulla Damluji, Scott A Bruce, Gordon Reeves, Amy M. Pastva, Alain G Bertoni, Robert J Mentz, David Whellan, Dalane Kitzman, Christopher R deFilippi
Introduction: Circulating biomarkers play an important role in patients with heart failure (HF) for risk stratification and mechanistic insights. We aimed to examine if a diverse set of biomarkers in the REHAB-HF trial would predict improvement in physical function following a 12-week tailored physical therapy rehabilitation intervention compared to attention control. Methods: The study population consisted of participants ≥60 years of age who were hospitalized with acute HF and randomized to a subsequent multidomain outpatient physical rehabilitation intervention vs. attention control with outcomes of 12-week functional change including the Short Physical Performance Battery (SPPB) and six-minute walk distance (6MWD). Blood was collected prior to randomization and at 12-weeks for cardiac, renal, and inflammatory biomarkers. Linear trends across progressively higher biomarker values versus improvement in functional outcomes based on treatment assignment were evaluated. Classification and regression trees (CART) were created to estimate optimal biomarker levels associated with differential improvement in the two functional outcomes. Results: A total of 242 of 349 participants (69%) had baseline biomarkers measured. In an adjusted regression model, higher baseline cardiac troponin (cTn) I and T were associated with greater gains in SPPB and 6MWD respectively with the rehabilitation intervention (P=0.04 and 0.03 for interaction) versus attention control. In the CART analysis of the physical rehabilitation and attention control participants, those with baseline C-reactive protein (CRP) ≥9.9 mg/L and hs-cTnT ≥36 ng/L receiving the rehabilitation intervention had a 129 m (95% CI 78-180m) greater 12-week 6MWD increase vs attention control. In contrast, for participants with CRP<9.9 mg/L there was no significant incremental 6MWD difference (30m, 95% CI -0.5m, 60.2m). For SPPB, a CRP ≥9.9 mg/L and creatinine ≥1.4 mg/dL optimally identified a differential improvement with the rehabilitation intervention versus attention control. The biomarkers (except for creatinine) decreased by 12 weeks post hospitalization but with no differences based on treatment assignment. Conclusion: Higher baseline levels of biomarkers of inflammation, cardiac injury, and renal dysfunction identified older adults after a HF hospitalization with the greatest differential improvement in physical function with a rehabilitation intervention. Biomarkers may help clinicians predict the benefits of this treatment.
{"title":"Circulating Biomarkers as Predictors of Improvement in Physical Function in Hospitalized Older Adults with Geriatric Syndromes: Findings from the REHAB-HF Trial","authors":"Abdulla Damluji, Scott A Bruce, Gordon Reeves, Amy M. Pastva, Alain G Bertoni, Robert J Mentz, David Whellan, Dalane Kitzman, Christopher R deFilippi","doi":"10.1101/2024.09.13.24313662","DOIUrl":"https://doi.org/10.1101/2024.09.13.24313662","url":null,"abstract":"Introduction: Circulating biomarkers play an important role in patients with heart failure (HF) for risk stratification and mechanistic insights. We aimed to examine if a diverse set of biomarkers in the REHAB-HF trial would predict improvement in physical function following a 12-week tailored physical therapy rehabilitation intervention compared to attention control. Methods: The study population consisted of participants ≥60 years of age who were hospitalized with acute HF and randomized to a subsequent multidomain outpatient physical rehabilitation intervention vs. attention control with outcomes of 12-week functional change including the Short Physical Performance Battery (SPPB) and six-minute walk distance (6MWD). Blood was collected prior to randomization and at 12-weeks for cardiac, renal, and inflammatory biomarkers. Linear trends across progressively higher biomarker values versus improvement in functional outcomes based on treatment assignment were evaluated. Classification and regression trees (CART) were created to estimate optimal biomarker levels associated with differential improvement in the two functional outcomes. Results: A total of 242 of 349 participants (69%) had baseline biomarkers measured. In an adjusted regression model, higher baseline cardiac troponin (cTn) I and T were associated with greater gains in SPPB and 6MWD respectively with the rehabilitation intervention (P=0.04 and 0.03 for interaction) versus attention control. In the CART analysis of the physical rehabilitation and attention control participants, those with baseline C-reactive protein (CRP) ≥9.9 mg/L and hs-cTnT ≥36 ng/L receiving the rehabilitation intervention had a 129 m (95% CI 78-180m) greater 12-week 6MWD increase vs attention control. In contrast, for participants with CRP<9.9 mg/L there was no significant incremental 6MWD difference (30m, 95% CI -0.5m, 60.2m). For SPPB, a CRP ≥9.9 mg/L and creatinine ≥1.4 mg/dL optimally identified a differential improvement with the rehabilitation intervention versus attention control. The biomarkers (except for creatinine) decreased by 12 weeks post hospitalization but with no differences based on treatment assignment. Conclusion: Higher baseline levels of biomarkers of inflammation, cardiac injury, and renal dysfunction identified older adults after a HF hospitalization with the greatest differential improvement in physical function with a rehabilitation intervention. Biomarkers may help clinicians predict the benefits of this treatment.","PeriodicalId":501297,"journal":{"name":"medRxiv - Cardiovascular Medicine","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142258350","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 : 2024-09-15DOI: 10.1101/2024.09.14.24313670
Stephen Burgess, Helene T Cronje, Emil deGoma, Yung Chyung, Dipender Gill
Background Abdominal aortic aneurysm (AAA) represents a significant cause of mortality, yet no medical therapies have proven efficacious. The aim of the current study was to leverage human genetic evidence to inform clinical development of interleukin-6 (IL6) signaling inhibition for treatment of AAA. Methods We focused on rs2228145, a missense variant in the IL6R gene region whose associations are expressed per additional copy of the C allele, corresponding to the genetically-predicted effect of IL6 signaling inhibition. We consider genetic associations with AAA risk in the AAAgen consortium (39,221 cases, 1,086,107 controls) and UK Biobank (2215 cases, 365,428 controls). To validate against known effects of IL6 signaling inhibition, we present associations with rheumatoid arthritis, polymyalgia rheumatica, and severe COVID-19. To explore mechanism specificity, we present associations with thoracic aortic aneurysm, intracranial aneurysm, and coronary artery disease. We further evaluated associations with measures of the abdominal aorta in UK Biobank, and explored genetic associations in clinically-relevant subgroups of the population. Results We observed strong genetic associations with AAA risk in the AAAgen consortium and in UK Biobank: odds ratio (OR) 0.91 (95% confidence interval [CI]: 0.90 to 0.92, p = 4x10-30) and OR 0.90 (95% CI: 0.84, 0.96, p=0.0007), respectively. The association with AAA risk in UK Biobank was linear in the number of minor alleles: OR 0.91 (95% CI: 0.83, 1.00) in heterozygotes and OR 0.80 (95% CI: 0.71, 0.92) in minor homozygotes. The association was similar for fatal AAA, but with greater uncertainty due to the lower number of events. The association with AAA was of greater magnitude than associations with coronary artery disease and even rheumatologic disorders for which IL6 inhibitors have been approved. No strong associations were observed with thoracic aortic aneurysm, intracranial aneurysm, or abdominal aorta diameter in the general population without AAA. Associations attenuated towards the null in populations with concomitant inflammatory or connective tissue disease. Conclusions This drug target Mendelian randomization study supports that IL6 signaling inhibition will be efficacious for treating AAA, but not other types of aneurysmal disease. These findings serve to help inform clinical development of IL6 signaling inhibition for AAA treatment.
{"title":"Human genetic evidence to inform clinical development of interleukin-6 signaling inhibition for abdominal aortic aneurysm","authors":"Stephen Burgess, Helene T Cronje, Emil deGoma, Yung Chyung, Dipender Gill","doi":"10.1101/2024.09.14.24313670","DOIUrl":"https://doi.org/10.1101/2024.09.14.24313670","url":null,"abstract":"Background\u0000Abdominal aortic aneurysm (AAA) represents a significant cause of mortality, yet no medical therapies have proven efficacious. The aim of the current study was to leverage human genetic evidence to inform clinical development of interleukin-6 (IL6) signaling inhibition for treatment of AAA. Methods\u0000We focused on rs2228145, a missense variant in the IL6R gene region whose associations are expressed per additional copy of the C allele, corresponding to the genetically-predicted effect of IL6 signaling inhibition. We consider genetic associations with AAA risk in the AAAgen consortium (39,221 cases, 1,086,107 controls) and UK Biobank (2215 cases, 365,428 controls). To validate against known effects of IL6 signaling inhibition, we present associations with rheumatoid arthritis, polymyalgia rheumatica, and severe COVID-19. To explore mechanism specificity, we present associations with thoracic aortic aneurysm, intracranial aneurysm, and coronary artery disease. We further evaluated associations with measures of the abdominal aorta in UK Biobank, and explored genetic associations in clinically-relevant subgroups of the population. Results\u0000We observed strong genetic associations with AAA risk in the AAAgen consortium and in UK Biobank: odds ratio (OR) 0.91 (95% confidence interval [CI]: 0.90 to 0.92, p = 4x10-30) and OR 0.90 (95% CI: 0.84, 0.96, p=0.0007), respectively. The association with AAA risk in UK Biobank was linear in the number of minor alleles: OR 0.91 (95% CI: 0.83, 1.00) in heterozygotes and OR 0.80 (95% CI: 0.71, 0.92) in minor homozygotes. The association was similar for fatal AAA, but with greater uncertainty due to the lower number of events. The association with AAA was of greater magnitude than associations with coronary artery disease and even rheumatologic disorders for which IL6 inhibitors have been approved. No strong associations were observed with thoracic aortic aneurysm, intracranial aneurysm, or abdominal aorta diameter in the general population without AAA. Associations attenuated towards the null in populations with concomitant inflammatory or connective tissue disease. Conclusions\u0000This drug target Mendelian randomization study supports that IL6 signaling inhibition will be efficacious for treating AAA, but not other types of aneurysmal disease. These findings serve to help inform clinical development of IL6 signaling inhibition for AAA treatment.","PeriodicalId":501297,"journal":{"name":"medRxiv - Cardiovascular Medicine","volume":"42 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142258349","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 : 2024-09-14DOI: 10.1101/2024.09.13.24313646
Pranav Sharma, Renae Judy, Shuai Yuan, Corry Gellatly, Katie L Saxby, Matthew J. Bown, Michael Levin, Scott M. Damrauer
Introduction: Lipoprotein(a) (Lp(a)) is a circulating apolipoprotein B (ApoB) containing particle that has been observationally linked to atherosclerotic cardiovascular disease and is the target of emerging therapeutics. Recent work has highlighted the role of circulating lipoproteins in abdominal aortic aneurysm (AAA). We sought to triangulate human observational and genetic evidence to evaluate the role of Lp(a) in AAA. Methods: We tested the association between circulating levels of Lp(a) and clinically diagnosed abdominal aortic aneurysms while controlling for traditional AAA risk factors and levels of ApoB using logistic regression among 795 individuals with and 374,772 individuals without AAA in the UK Biobank (UKB). Multivariable Mendelian randomization (MVMR) was used to test for putatively causal associations between Lp(a) and AAA controlling for ApoB. Genetic instruments for Lp(a) and ApoB were created from genome-wide association studies (GWAS) of Lp(a) and ApoB comprising 335,796 and 418,505 UKB participants, respectively. The instruments were tested for association with AAA using data from a GWAS of 39,221 individuals with and 1,086,107 without AAA. Results: Elevated Lp(a) levels were observationally associated with an increased risk of AAA (OR 1.04 per 10 nmol/L Lp(a); 95%CI 1.02-1.05; P<0.01). Clinically elevated Lp(a) levels (>150nmol/L) were likewise associated with an increased risk of AAA (OR 1.47; 95% CI 1.15-1.88; P < 0.01) when compared to individuals with Lp(a) levels <150nmol/L. MVMR confirmed a significant, ApoB-independent association between increased Lp(a) and increased risk of AAA (OR 1.13 per SD increase in Lp(a); 95%CI 1.02-1.24; P<0.02). Conclusion: Both observational and genetic analyses support an association between increased Lp(a) and AAA risk that is independent of ApoB. These findings suggest that Lp(a) may be a therapeutic target for AAA and drive the inclusion of AAA as an outcome in clinical trials of Lp(a) antagonists.
{"title":"Lipoprotein (a) is associated with increased risk of Abdominal Aortic Aneurysm","authors":"Pranav Sharma, Renae Judy, Shuai Yuan, Corry Gellatly, Katie L Saxby, Matthew J. Bown, Michael Levin, Scott M. Damrauer","doi":"10.1101/2024.09.13.24313646","DOIUrl":"https://doi.org/10.1101/2024.09.13.24313646","url":null,"abstract":"Introduction: Lipoprotein(a) (Lp(a)) is a circulating apolipoprotein B (ApoB) containing particle that has been observationally linked to atherosclerotic cardiovascular disease and is the target of emerging therapeutics. Recent work has highlighted the role of circulating lipoproteins in abdominal aortic aneurysm (AAA). We sought to triangulate human observational and genetic evidence to evaluate the role of Lp(a) in AAA.\u0000Methods: We tested the association between circulating levels of Lp(a) and clinically diagnosed abdominal aortic aneurysms while controlling for traditional AAA risk factors and levels of ApoB using logistic regression among 795 individuals with and 374,772 individuals without AAA in the UK Biobank (UKB). Multivariable Mendelian randomization (MVMR) was used to test for putatively causal associations between Lp(a) and AAA controlling for ApoB. Genetic instruments for Lp(a) and ApoB were created from genome-wide association studies (GWAS) of Lp(a) and ApoB comprising 335,796 and 418,505 UKB participants, respectively. The instruments were tested for association with AAA using data from a GWAS of 39,221 individuals with and 1,086,107 without AAA. Results: Elevated Lp(a) levels were observationally associated with an increased risk of AAA (OR 1.04 per 10 nmol/L Lp(a); 95%CI 1.02-1.05; P<0.01). Clinically elevated Lp(a) levels (>150nmol/L) were likewise associated with an increased risk of AAA (OR 1.47; 95% CI 1.15-1.88; P < 0.01) when compared to individuals with Lp(a) levels <150nmol/L. MVMR confirmed a significant, ApoB-independent association between increased Lp(a) and increased risk of AAA (OR 1.13 per SD increase in Lp(a); 95%CI 1.02-1.24; P<0.02).\u0000Conclusion: Both observational and genetic analyses support an association between increased Lp(a) and AAA risk that is independent of ApoB. These findings suggest that Lp(a) may be a therapeutic target for AAA and drive the inclusion of AAA as an outcome in clinical trials of Lp(a) antagonists.","PeriodicalId":501297,"journal":{"name":"medRxiv - Cardiovascular Medicine","volume":"23 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142258372","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}
This case report demonstrates the feasibility of creating immersive 3D visualizations ( 3D Virtual reality and 3D printing) from fetal echocardiographic volume datasets for both normal heart and a heart with transposition of great arteries. Immersive 3D technologies could emerge as powerful tools in future for understanding fetal cardiac anatomy for clinical decision making as well as training and research.
{"title":"Three-Dimensional virtual reality-based visualization of fetal cardiac anatomy using spatio-temporal image correlation (STIC) ultrasound datasets of normal and abnormal hearts.","authors":"Balu Vaidyanathan, Harikrishnan Anil Maya, Sarin Xavier, Mahesh Kappanayil","doi":"10.1101/2024.09.11.24313355","DOIUrl":"https://doi.org/10.1101/2024.09.11.24313355","url":null,"abstract":"This case report demonstrates the feasibility of creating immersive 3D visualizations ( 3D Virtual reality and 3D printing) from fetal echocardiographic volume datasets for both normal heart and a heart with transposition of great arteries. Immersive 3D technologies could emerge as powerful tools in future for understanding fetal cardiac anatomy for clinical decision making as well as training and research.","PeriodicalId":501297,"journal":{"name":"medRxiv - Cardiovascular Medicine","volume":"11 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142258375","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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