Fadi Adel, Adel Kabbara Allababidi, Yogesh N V Reddy
{"title":"Hepatopulmonary Syndrome or Portopulmonary Hypertension? Two Contrasting Cases of Exertional Hypoxemia From Liver Disease.","authors":"Fadi Adel, Adel Kabbara Allababidi, Yogesh N V Reddy","doi":"10.1161/CIRCHEARTFAILURE.124.012506","DOIUrl":"https://doi.org/10.1161/CIRCHEARTFAILURE.124.012506","url":null,"abstract":"","PeriodicalId":10196,"journal":{"name":"Circulation: Heart Failure","volume":" ","pages":"e012506"},"PeriodicalIF":7.8,"publicationDate":"2025-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143623686","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Simon Vanhentenrijk, Justin L Grodin, Silvio Nunes Augusto, W H Wilson Tang
{"title":"Hereditary Transthyretin Cardiac Amyloidosis With the p.V142I Variant: Mechanistic Insights and Diagnostic Challenges.","authors":"Simon Vanhentenrijk, Justin L Grodin, Silvio Nunes Augusto, W H Wilson Tang","doi":"10.1161/CIRCHEARTFAILURE.124.012469","DOIUrl":"https://doi.org/10.1161/CIRCHEARTFAILURE.124.012469","url":null,"abstract":"<p><p>The most common form of hereditary transthyretin cardiac amyloidosis (hATTR-CA) in the United States and the United Kingdom is the p.V142I variant. About 3% to 4% of patients with African ancestry carry this genetic predisposition to develop signs and symptoms of hATTR-CA. Nevertheless, clinical manifestations of hATTR-CA appear only late in the fifth and sixth decades of life, despite its clear genetic background. Imbalances in native protein-stabilizing and elementary breakdown cellular mechanisms are postulated as potential causes for affecting transthyretin structural integrity and myocardial fibril deposition. Noncoding variants, epigenetic and environmental factors, as well as gut microbiome derangements may serve as disease-modifying factors that feature detrimental amyloidogenic organ involvement and impact disease severity. Organ amyloid deposition varies widely among different carriers of a genetic transthyretin variant. The genotype-phenotype interdependence causes unpredictable phenotypic penetrance that results in a variety of signs and symptoms and patient outcomes. Cardiovascular biomarkers and multimodality imaging may identify initial amyloidogenic organ involvement. These early clinical clues through the course of hATTR-CA offer a window of opportunity for early treatment onset to cease disease progression and alter prognosis. Identifying at-risk patients requires information on the genetic background of probands and their relatives. Initiatives to reveal asymptomatic gene carriers early in the disease should be encouraged, as it necessitates stringent patient follow-up and immediate treatment onset to reduce the burden of heart failure hospitalization and mortality in hATTR-CA.</p>","PeriodicalId":10196,"journal":{"name":"Circulation: Heart Failure","volume":" ","pages":"e012469"},"PeriodicalIF":7.8,"publicationDate":"2025-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143623687","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Precision Medicine Is in the Eye of the Beholder.","authors":"Kenneth B Margulies","doi":"10.1161/CIRCHEARTFAILURE.125.012759","DOIUrl":"https://doi.org/10.1161/CIRCHEARTFAILURE.125.012759","url":null,"abstract":"","PeriodicalId":10196,"journal":{"name":"Circulation: Heart Failure","volume":" ","pages":"e012759"},"PeriodicalIF":7.8,"publicationDate":"2025-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143596409","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Kyohei Fujita, Patrick Desmond, Jordan Blondelle, Matúš Soták, Meenu Rohini Rajan, Madison Clark, Éric Estève, Yunghang Chan, Yusu Gu, Virginia Actis Dato, Valeria Marrocco, Nancy D Dalton, Majid Ghassemian, Aryanne Do, Matthew Klos, Kirk L Peterson, Farah Sheikh, Yoshitake Cho, Emma Börgeson, Stephan Lange
{"title":"Combined Loss of Obsc and Obsl1 in Murine Hearts Results in Diastolic Dysfunction, Altered Metabolism, and Deregulated Mitophagy.","authors":"Kyohei Fujita, Patrick Desmond, Jordan Blondelle, Matúš Soták, Meenu Rohini Rajan, Madison Clark, Éric Estève, Yunghang Chan, Yusu Gu, Virginia Actis Dato, Valeria Marrocco, Nancy D Dalton, Majid Ghassemian, Aryanne Do, Matthew Klos, Kirk L Peterson, Farah Sheikh, Yoshitake Cho, Emma Börgeson, Stephan Lange","doi":"10.1161/CIRCHEARTFAILURE.124.011867","DOIUrl":"https://doi.org/10.1161/CIRCHEARTFAILURE.124.011867","url":null,"abstract":"<p><strong>Background: </strong>Muscle proteins of the obscurin protein family play important roles in sarcomere organization and sarcoplasmic reticulum and T-tubule architecture and function. However, their precise molecular functions and redundancies between protein family members as well as their involvement in cardiac diseases remain to be fully understood.</p><p><strong>Methods: </strong>To investigate the functional roles of Obsc (obscurin) and its close homolog Obsl1 (obscurin-like 1) in the heart, we generated and analyzed knockout mice for <i>Obsc</i>, <i>Obsl1</i>, as well as <i>Obsc/Obsl1</i> double knockouts.</p><p><strong>Results: </strong>We show that double-knockout mice are viable but show postnatal deficits in cardiac muscle sarcoplasmic reticulum and mitochondrial architecture and function at the microscopic, biochemical, and cellular levels. Altered sarcoplasmic reticulum structure resulted in perturbed calcium cycling, whereas mitochondrial ultrastructure deficits were linked to decreased levels of Chchd3 (coiled-coil-helix-coiled-coil-helix domain containing 3), a Micos (mitochondrial contact site and cristae organizing system) complex protein. Hearts of double-knockout mice also show altered levels of Atg4 proteins, novel Obsl1 interactors, resulting in abnormal mitophagy, and increased unfolded protein response. At the physiological level, loss of obscurin and Obsl1 resulted in a profound delay of cardiac relaxation, associated with metabolic signs of heart failure.</p><p><strong>Conclusions: </strong>Taken together, our data suggest that Obsc and Obsl1 play crucial roles in cardiac sarcoplasmic reticulum structure, calcium cycling, mitochondrial function, turnover, and metabolism.</p>","PeriodicalId":10196,"journal":{"name":"Circulation: Heart Failure","volume":" ","pages":"e011867"},"PeriodicalIF":7.8,"publicationDate":"2025-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143596354","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Sanjiv J Shah, Diana Bonderman, Barry A Borlaug, John G F Cleland, Gabriela Lack, Wentao Lu, Adriaan A Voors, Faiez Zannad, Mark T Gladwin
{"title":"Macitentan for Heart Failure With Preserved or Mildly Reduced Ejection Fraction and Pulmonary Vascular Disease: Results of the SERENADE Randomized Clinical Trial and Open-Label Extension Study.","authors":"Sanjiv J Shah, Diana Bonderman, Barry A Borlaug, John G F Cleland, Gabriela Lack, Wentao Lu, Adriaan A Voors, Faiez Zannad, Mark T Gladwin","doi":"10.1161/CIRCHEARTFAILURE.123.011381","DOIUrl":"10.1161/CIRCHEARTFAILURE.123.011381","url":null,"abstract":"<p><strong>Background: </strong>Despite favorable hemodynamic and neurohormonal effects, endothelin receptor antagonists have not improved outcomes in patients with heart failure (HF), possibly because they cause fluid retention.</p><p><strong>Methods: </strong>In this randomized, double-blind, multicenter trial (SERENADE [Macitentan in Heart Failure With Preserved Ejection Fraction and Pulmonary Vascular Disease]), we evaluated the effects of an endothelin receptor antagonist, macitentan, in patients with HF, left ventricular ejection fraction ≥40%, and pulmonary vascular disease. After a 4-week placebo run-in (to ensure clinical stability), followed by a 5-week single-blind macitentan run-in, patients who did not exhibit fluid retention were randomized to macitentan or placebo. The primary end point was change in NT-proBNP (N-terminal pro-B-type natriuretic peptide; baseline to 24 weeks); secondary end points included change in KCCQ (Kansas City Cardiomyopathy Questionnaire) clinical summary score (baseline to 24 weeks) and time to worsening HF by 52 weeks.</p><p><strong>Results: </strong>Of 230 patients enrolled, 28 were excluded during the placebo run-in, 60 excluded during the macitentan run-in, and 142 were randomized. Macitentan had no effect on change in NT-proBNP (geometric mean ratio [macitentan/placebo], 1.02 [90% CI, 0.88-1.19]; <i>P</i>=0.79) or on secondary end points (placebo-corrected change in KCCQ clinical summary score, -3.5 [90% CI, -8.2 to +1.2]; <i>P</i>=0.22). Worsening HF occurred in 20 (28%) patients assigned to macitentan and 13 (18%) assigned to placebo (hazard ratio, 1.48 [90% CI, 0.83-2.67]; <i>P</i>=0.24). More macitentan-treated patients developed fluid retention (16 [23%] versus 10 [14%]) and cardiac adverse events (33 [46%] versus 22 [31%]) versus placebo.</p><p><strong>Conclusions: </strong>Despite a novel enrichment trial design to target pulmonary vascular disease and exclude treatment-related fluid retention in patients with HF and preserved/mildly reduced left ventricular ejection fraction, macitentan neither lowered NT-proBNP nor improved HF outcomes.</p><p><strong>Registration: </strong>URL: https://www.clinicaltrials.gov; Unique identifiers: NCT03153111 and NCT03714815.</p>","PeriodicalId":10196,"journal":{"name":"Circulation: Heart Failure","volume":" ","pages":"e011381"},"PeriodicalIF":7.8,"publicationDate":"2025-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143596359","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Natasha L Altman, Edward A Gill, Rami Kahwash, Leslie K Meyer, Jessica A Wagner, Anis Karimpour-Fard, Amber A Berning, Wayne A Minobe, Ian A Carroll, Eric R Jonas, Dobromir Slavov, Sitaramesh Emani, William T Abraham, Alexa R Gollah, Samuel L Ellis, Matthew R G Taylor, Sharon L Graw, Luisa Mestroni, Timothy A McKinsey, Peter M Buttrick, David P Kao, Michael R Bristow
{"title":"Heart Rate Reduction Is Associated With Reverse Left Ventricular Remodeling and Mechanism-Specific Molecular Phenotypes in Dilated Cardiomyopathy.","authors":"Natasha L Altman, Edward A Gill, Rami Kahwash, Leslie K Meyer, Jessica A Wagner, Anis Karimpour-Fard, Amber A Berning, Wayne A Minobe, Ian A Carroll, Eric R Jonas, Dobromir Slavov, Sitaramesh Emani, William T Abraham, Alexa R Gollah, Samuel L Ellis, Matthew R G Taylor, Sharon L Graw, Luisa Mestroni, Timothy A McKinsey, Peter M Buttrick, David P Kao, Michael R Bristow","doi":"10.1161/CIRCHEARTFAILURE.124.012484","DOIUrl":"https://doi.org/10.1161/CIRCHEARTFAILURE.124.012484","url":null,"abstract":"<p><strong>Background: </strong>Heart rate (HR) affects heart failure outcomes, via uncertain mechanisms that may include left ventricular remodeling. However, in human ventricular myocardium, HR change has not been associated with a particular remodeling molecular phenotype.</p><p><strong>Methods: </strong>Patients with nonischemic dilated cardiomyopathy (N=22) in sinus rhythm and refractory to β-blockade for both HR lowering and reverse remodeling were randomized 2:1 double-blind to the HCN4 (hyperpolarization-activated cyclic nucleotide-gated potassium channel 4) channel inhibitor ivabradine or placebo for 24 weeks treatment while maintaining target doses of β-blockers. Reverse remodeling was measured by left ventricular ejection fraction (LVEF), and myocardial gene expression by sequencing RNA extracted from endomyocardial biopsies. The primary statistical analysis was between HR change categories divided at the median, which resulted in Decreased HR (N=90) and Unchanged HR (N=8) groups.</p><p><strong>Results: </strong>Respective HRs at baseline and 24 weeks were as follows: Decreased HR, 82.9±6.8 and 69.7±8.0 beats per minute (<i>P</i>=0.0005) and Unchanged HR, 80.8±5.7 and 79.2±11.6 beats per minute (<i>P</i>=0.58). All completing Decreased HR subjects were treated with ivabradine, whereas in the Unchanged HR group, 3 received ivabradine and 5 placebo. In Decreased HR, LVEF increased from 29.4±8.8% at baseline to 44.2±9.4% at 24 weeks (<i>P</i>=0.0003), compared with respective values of 26.6±11.4% and 29.2±12.0% (<i>P</i>=0.28) in Unchanged HR. HR and LVEF changes were not different from a previously conducted β-blocker nonischemic dilated cardiomyopathy study subdivided into LVEF responders and nonresponders. However, differentially expressed genes (N=151) in the Decreased versus Unchanged HR groups were >99% nonconcordant and therefore individually unique compared with β-blocker HR/LVEF responders versus nonresponders (2 shared differentially expressed genes). Multiple unique differentially expressed genes in Decreased HR including <i>NRG1</i> upregulation are considered cardioprotective or involved in cardiac development.</p><p><strong>Conclusions: </strong>In patients with nonischemic dilated cardiomyopathy in sinus rhythm, HR lowering per se (1) is associated with substantial left ventricular reverse remodeling; (2) its absence can cause β-blocker reverse remodeling nonresponse; and (3) when from HCN4 channel inhibition, results in a unique molecular phenotype.</p><p><strong>Registration: </strong>URL: https://www.clinicaltrials.gov; Unique identifier: NCT02973594.</p>","PeriodicalId":10196,"journal":{"name":"Circulation: Heart Failure","volume":" ","pages":"e012484"},"PeriodicalIF":7.8,"publicationDate":"2025-03-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143572332","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Jessica Chadwick, Michael A Hinterberg, Folkert W Asselbergs, Hannah Biegel, Eric Boersma, Thomas P Cappola, Julio A Chirinos, Joseph Coresh, Peter Ganz, David A Gordon, Natasha Kureshi, Kelsey M Loupey, Alena Orlenko, Rachel Ostroff, Laura Sampson, Sama Shrestha, Nancy K Sweitzer, Stephen A Williams, Lei Zhao, Isabella Kardys, David E Lanfear
{"title":"Harnessing the Plasma Proteome to Predict Mortality in Heart Failure Subpopulations.","authors":"Jessica Chadwick, Michael A Hinterberg, Folkert W Asselbergs, Hannah Biegel, Eric Boersma, Thomas P Cappola, Julio A Chirinos, Joseph Coresh, Peter Ganz, David A Gordon, Natasha Kureshi, Kelsey M Loupey, Alena Orlenko, Rachel Ostroff, Laura Sampson, Sama Shrestha, Nancy K Sweitzer, Stephen A Williams, Lei Zhao, Isabella Kardys, David E Lanfear","doi":"10.1161/CIRCHEARTFAILURE.123.011208","DOIUrl":"https://doi.org/10.1161/CIRCHEARTFAILURE.123.011208","url":null,"abstract":"<p><strong>Background: </strong>We derived and validated proteomic risk scores (PRSs) for heart failure (HF) prognosis that provide absolute risk estimates for all-cause mortality within 1 year.</p><p><strong>Methods: </strong>Plasma samples from individuals with HF with reduced ejection fraction (HFrEF; ejection fraction <40%; training/validation n=1247/762) and preserved ejection fraction (HFpEF; ejection fraction ≥50%; training/validation n=725/785) from 3 independent studies were run on the SomaScan Assay measuring ≈5000 proteins. Machine learning techniques resulted in unique 17- and 14-protein models for HFrEF and HFpEF that predict 1-year mortality. Discrimination was assessed via C-index and 1-year area under the curve (AUC), and survival curves were visualized. PRSs were also compared with Meta-Analysis Global Group in Chronic HF (MAGGIC) score and NT-proBNP (N-terminal pro-B-type natriuretic peptide) measurements and further assessed for sensitivity to disease progression in longitudinal samples (HFrEF: n=396; 1107 samples; HFpEF: n=175; 350 samples).</p><p><strong>Results: </strong>In validation, the HFpEF PRS performed significantly better (<i>P</i>≤0.1) for mortality prediction (C-index, 0.79; AUC, 0.82) than MAGGIC (C-index, 0.71; AUC, 0.74) and NT-proBNP (PRS C-index, 0.76 and AUC, 0.81 versus NT-proBNP C-index, 0.72 and AUC, 0.76). The HFrEF PRS performed comparably to MAGGIC (PRS C-index, 0.76 and AUC, 0.83 versus MAGGIC C-index, 0.75 and AUC, 0.84) but had a significantly better C-Index (<i>P</i>=0.026) than NT-proBNP (PRS C-index, 0.75 and AUC, 0.78 versus NT-proBNP C-index, 0.73 and AUC, 0.77). PRS included known HF pathophysiology biomarkers (93%) and novel proteins (7%). Longitudinal assessment revealed that HFrEF and HFpEF PRSs were higher and increased more over time in individuals who experienced a fatal event during follow-up.</p><p><strong>Conclusions: </strong>PRSs can provide valid, accurate, and dynamic prognostic estimates for patients with HF. This approach has the potential to improve longitudinal monitoring of patients and facilitate personalized care.</p>","PeriodicalId":10196,"journal":{"name":"Circulation: Heart Failure","volume":" ","pages":"e011208"},"PeriodicalIF":7.8,"publicationDate":"2025-03-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143572318","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Shubhadarshini Pawar, Kannu Bansal, J Dawn Abbott, Manreet K Kanwar, Navin K Kapur, Van-Khue Ton, Saraschandra Vallabhajosyula
{"title":"Transfer to Hub Hospitals and Outcomes in Cardiogenic Shock.","authors":"Shubhadarshini Pawar, Kannu Bansal, J Dawn Abbott, Manreet K Kanwar, Navin K Kapur, Van-Khue Ton, Saraschandra Vallabhajosyula","doi":"10.1161/CIRCHEARTFAILURE.124.012477","DOIUrl":"https://doi.org/10.1161/CIRCHEARTFAILURE.124.012477","url":null,"abstract":"<p><strong>Background: </strong>There are limited large-scale data on the outcomes of patients with cardiogenic shock (CS) transferred to hub centers. This study aimed to compare the characteristics and outcomes of transferred patients with CS versus those who were not transferred.</p><p><strong>Methods: </strong>Adults (aged ≥18 years) with a primary or secondary diagnosis of CS were identified from the Nationwide Readmissions Database (2016-2020) and stratified by transfer status. Overlap propensity score weighting was performed to assess the association between transfer status and in-hospital mortality. Secondary outcomes, including length of hospital stay, hospitalization costs, and readmissions for cardiac and noncardiac etiologies, were assessed using multivariable regression.</p><p><strong>Results: </strong>Of 314 098 patients with CS (27% with acute myocardial infarction-related CS and 73% with nonacute myocardial infarction-related CS), 30 630 (9.8%) were transferred. In the unweighted population, compared with nontransferred patients, transferred patients were on average younger (65 versus 68 years), had higher comorbidities, and were more likely to be cared for at large teaching hospitals. During the hospitalization, they had higher rates of renal failure, pulmonary artery catheter use, and mechanical circulatory support use. In-hospital mortality was lower in transferred patients-39.1% versus 47.1%; unadjusted odds ratio (OR), 0.71 (95% CI, 0.70-0.73); adjusted OR, 0.73 ([95% CI, 0.71-0.76]; <i>P</i><0.001). This was consistent across subgroups of CS cause, age, sex, hospital location, mechanical circulatory support use, and presence of cardiac arrest. The transferred cohort had lower costs and length of stay, but more frequent all-cause (adjusted OR, 1.21 [95% CI, 1.16-1.27]), cardiac (adjusted OR, 1.16 [95% CI, 1.11-1.22]), heart failure (adjusted OR, 1.14 [95% CI, 1.08-1.21]), and noncardiac readmissions (adjusted OR, 1.68 [95% CI, 1.21-2.33]) at 30 days postdischarge compared with the nontransferred cohort.</p><p><strong>Conclusions: </strong>Despite higher comorbidity, organ failure, and use of cardiac/noncardiac procedures, patients with CS who were transferred to hub centers had lower in-hospital mortality, hospitalization costs, and length of stay.</p>","PeriodicalId":10196,"journal":{"name":"Circulation: Heart Failure","volume":" ","pages":"e012477"},"PeriodicalIF":7.8,"publicationDate":"2025-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143556039","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Alexander C Egbe, Yogesh N V Reddy, William R Miranda, C Charles Jain, Heidi M Connolly, Barry A Borlaug
{"title":"Hemodynamics of Exercise-Induced Hypertension and Relationship to Outcomes in Adults With Coarctation of the Aorta.","authors":"Alexander C Egbe, Yogesh N V Reddy, William R Miranda, C Charles Jain, Heidi M Connolly, Barry A Borlaug","doi":"10.1161/CIRCHEARTFAILURE.124.012459","DOIUrl":"https://doi.org/10.1161/CIRCHEARTFAILURE.124.012459","url":null,"abstract":"<p><strong>Background: </strong>Exercise-induced hypertension (EIH) is common in adults with coarctation of the aorta (COA), but there are limited data about hemodynamics and outcomes in such patients. The purpose of this study was to assess changes in arterial load during exercise in patients with COA with versus without EIH, and the relationship to clinical outcomes.</p><p><strong>Methods: </strong>We compared Doppler-derived arterial load indices (effective arterial elastance index, total arterial compliance index, systemic vascular resistance index), and clinical indices of disease severity (pulmonary congestion, aerobic capacity, and cardiovascular biomarkers) between adults with repaired COA and healthy controls. EIH was defined as systolic blood pressure (BP) at peak exercise >210 mm Hg in men or >190 mm Hg in women.</p><p><strong>Results: </strong>In this prospective cohort study, we assessed patients with COA (n=41, age 43±14 years, 26 [63%] men) and healthy controls (n=41). Although both groups had similar resting systolic BP, the COA group had higher Doppler-derived arterial load indices at rest, as well as a greater rise in systolic BP and Doppler-derived arterial load indices at each stage of exercise, leading to a higher prevalence of EIH in the COA group (37% versus 10%; <i>P</i>=0.004). Compared with patients with COA without EIH (n=26, 63%), those with EIH had higher arterial load at rest and during exercise, as well as worse cardiac dysfunction, pulmonary congestion, and biomarkers of cardiovascular remodeling, despite no significant differences in resting systolic BP.</p><p><strong>Conclusions: </strong>BP assessment during exercise can improve risk stratification and identify patients who may benefit from intensification of medical therapy.</p>","PeriodicalId":10196,"journal":{"name":"Circulation: Heart Failure","volume":" ","pages":"e012459"},"PeriodicalIF":7.8,"publicationDate":"2025-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143556037","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Mingming Yang, Toru Kondo, Pooja Dewan, Akshay S Desai, Carolyn S P Lam, Martin P Lefkowitz, Milton Packer, Jean L Rouleau, Muthiah Vaduganathan, Michael R Zile, Pardeep S Jhund, Lars Køber, Scott D Solomon, John J V McMurray
{"title":"Impact of Multimorbidity on Mortality in Heart Failure With Mildly Reduced and Preserved Ejection Fraction.","authors":"Mingming Yang, Toru Kondo, Pooja Dewan, Akshay S Desai, Carolyn S P Lam, Martin P Lefkowitz, Milton Packer, Jean L Rouleau, Muthiah Vaduganathan, Michael R Zile, Pardeep S Jhund, Lars Køber, Scott D Solomon, John J V McMurray","doi":"10.1161/CIRCHEARTFAILURE.124.011598","DOIUrl":"https://doi.org/10.1161/CIRCHEARTFAILURE.124.011598","url":null,"abstract":"<p><strong>Background: </strong>How different combinations of comorbidities influence risk at the patient level and population level in patients with heart failure with mildly reduced ejection fraction/heart failure with preserved ejection fraction is unknown. We aimed to investigate the prevalence of different combinations of cardiovascular and noncardiovascular comorbidities (ie, multimorbidity) and associated risk of death at the patient level and population level.</p><p><strong>Methods: </strong>Using patient-level data from the TOPCAT trial (Treatment of Preserved Cardiac Function Heart Failure With an Aldosterone Antagonist) and PARAGON-HF trial (Prospective Comparison of ARNI With ARB Global Outcomes in HF With Preserved Ejection Fraction), we investigated the 5 most common cardiovascular and noncardiovascular comorbidities and the resultant 45 comorbidity pairs. Cox proportional hazard models were used to calculate the population-attributable fractions for all-cause mortality and the relative excess risk due to interaction for each comorbidity pair.</p><p><strong>Results: </strong>Among 6504 participants, 95.2% had at least 2 of the 10 most prevalent comorbidities. The comorbidity pair with the greatest patient-level risk was stroke and peripheral artery disease (adjusted hazard ratio, 1.88 [95% CI, 1.27-2.79]), followed by peripheral artery disease and chronic obstructive pulmonary disease (1.81 [95% CI, 1.31-2.51]), and coronary artery disease and stroke (1.67 [95% CI, 1.33-2.11]). The pair with the highest population-level risk was hypertension and chronic kidney disease (CKD; adjusted population-attributable fraction, 14.8% [95% CI, 9.2%-19.9%]), followed by diabetes and CKD (13.3% [95% CI, 10.6%-16.0%]), and hypertension and diabetes (11.9% [95% CI, 7.1%-16.5%). A synergistic interaction (more than additive risk) was found for the comorbidity pairs of stroke and coronary artery disease (relative excess risk due to interaction, 0.61 [95% CI, 0.13-1.09]), diabetes and CKD (relative excess risk due to interaction, 0.46 [95% CI, -0.15 to 0.77]), and obesity and CKD (relative excess risk due to interaction, 0.24 [95% CI, 0.01-0.46]).</p><p><strong>Conclusions: </strong>The risk associated with comorbidity pairs differs at the patient and population levels in heart failure with mildly reduced ejection fraction/heart failure with preserved ejection fraction. At the population level, hypertension, CKD, and diabetes account for the greatest risk, whereas at the patient level, polyvascular disease and chronic obstructive pulmonary disease are the most important.</p>","PeriodicalId":10196,"journal":{"name":"Circulation: Heart Failure","volume":" ","pages":"e011598"},"PeriodicalIF":7.8,"publicationDate":"2025-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143536613","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}