Stroke; A Journal Of Cerebral Circulation[JOURNAL]
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200 papers
Observational Comparative Research in Cardiovascular and Brain Health and Disease: A Scientific Statement From the American Heart Association.
Mac Grory B, Yeh RW, Beckman JA … +11 more , Kamel H, Lusk JB, Otto CM, Shi J, Smith EE, Xian Y, Zachrison KS, American Heart Association Stroke Council, Council on Clinical Cardiology, Council on Peripheral Vascular Disease, Council on Quality of Care and Outcomes Research
Circulation · 2026 Jun · PMID 42158988 · Publisher ↗
Resources for observational comparative research have expanded enormously in recent years to include very large sources of granular, routinely collected health care data and modern statistical, epidemiologic, and econome...
Resources for observational comparative research have expanded enormously in recent years to include very large sources of granular, routinely collected health care data and modern statistical, epidemiologic, and econometric techniques. This scientific statement provides an overview of best practices and analytic considerations in observational comparative studies from the perspective of investigators, sponsors, publishers, and consumers of observational research. Observational comparative research is a component of the research landscape that fulfills a role distinct from that of interventional studies in the evaluation of drugs, surgical procedures, medical devices, and health policies. Sources of systematic error (ie, bias) in observational comparative studies include selection bias, information bias, and confounding. Principles from statistical science and econometrics can potentially be used to make causal conclusions from observational data. Target trial emulation is a useful framework to guide the rational design and illuminate the limitations of observational studies. As with interventional research, a formal study protocol should be prepared before every observational study to enhance rigor, reduce data manipulation, and promote transparency of study reporting. Selection of the study data source is a key decision early in the design stage of a study, and should be chosen on the basis of concordance between the needs of the specific study question and the properties of the data set. We recommend the use of causal directed acyclic graphs to clearly specify the study exposure, end points, confounders, colliders, moderators, and mediators. Taken together, these recommendations promote rational design choices and cautious interpretation of the results of observational comparative studies.
Implications of Cranial Arterial Stenosis and Dolichoectasia for Cerebral Small-Vessel Disease Etiopathogenesis: Findings From a Prospective Mild Stroke Cohort.
Han F, Clancy U, Arteaga-Reyes C … +19 more , Thrippleton MJ, Valdés Hernández MDC, Jaime Garcia D, Stringer MS, Backhouse E, Chappell FM, Cheng Y, Liu DX, Zhang J, Jochems ACC, Sakka E, Jardine C, Barclay G, McIntyre D, Hamilton I, Brown R, Zhu YC, Doubal FN, Wardlaw JM
Circulation · 2026 Jun · PMID 42090170 · Full text
BACKGROUND: Stenosis and dolichoectasia of cranial arteries likely reflect distinct mechanisms. Their contributions to lacunar stroke and cerebral small-vessel disease (cSVD) remain contentious. We investigated the assoc...
BACKGROUND: Stenosis and dolichoectasia of cranial arteries likely reflect distinct mechanisms. Their contributions to lacunar stroke and cerebral small-vessel disease (cSVD) remain contentious. We investigated the associations of large-artery stenosis (LAS) and arterial widening with stroke subtype, cSVD markers, incident infarcts, and clinical outcomes. METHODS: We prospectively recruited patients with lacunar or mild nonlacunar stroke, with demographic, stroke-related, cognitive, functional, and magnetic resonance imaging (index and incident infarcts, cSVD markers) assessments at baseline and 1 year. LAS was defined as ≥50% intracranial or cervical artery stenosis; basilar artery dolichoectasia was defined by basilar artery diameter, bifurcation height, and lateral displacement; and intracranial carotid and middle cerebral artery diameters were also measured. Associations were estimated from multivariable logistic, linear, and proportional odds regression models adjusted for age, sex, and vascular risk factors. We further conducted a systematic literature review to synthesize evidence on relationships between large-artery pathology and cSVD. RESULTS: Among 229 patients (mean age, 65.9±11.1 years; 131 [57.2%] lacunar stroke), LAS and basilar artery dolichoectasia were present in 20.5% and 15.7%, respectively. After adjustment, LAS (odds ratio, 0.49 [95% CI, 0.23-0.99]) and the presence of any embolic source were associated with lower odds of lacunar versus non-lacunar stroke, and not with cSVD markers or incident infarcts. In contrast, basilar artery dolichoectasia was strongly associated with lacunar stroke (odds ratio, 4.67 [95% CI, 1.87-13.14]), higher cSVD scores (ordinal analysis; odds ratio, 2.57 [95% CI, 1.28-5.25]), incident infarcts (75% subcortical; odds ratio, 2.29 [95% CI, 1.01-5.14]), and greater progression of white matter hyperintensities over 1 year (β, 0.15 [95% CI, 0.01-0.29] per log-transformed volume). Similar associations were observed for wider intracranial arteries. The systematic review supported these findings. CONCLUSIONS: cSVD, including lacunar stroke, was unrelated to LAS but strongly associated with dolichoectasia and wider arteries. These findings support a nonatheromatous, intrinsic microvascular pathology, particularly segmental arteriolar disorganization, as the principal mechanism of lacunar stroke and cSVD. Mechanism-specific diagnostic and therapeutic strategies are warranted.
Modest Contribution of Bradykinin to Blood Pressure Reduction by Sacubitril/Valsartan in Chronic Heart Failure.
Gupta DK, Stevenson LW, Garner EM … +6 more , Maulion C, Nian H, Wright PR, Turcu AF, Wei S, Brown NJ
Circ Heart Fail · 2026 Jun · PMID 42028604 · Full text
BACKGROUND: Symptomatic hypotension can limit sacubitril/valsartan therapy. Neprilysin inhibition may augment vasodilators, such as bradykinin. We hypothesized that bradykinin contributes to blood pressure (BP) lowering...
BACKGROUND: Symptomatic hypotension can limit sacubitril/valsartan therapy. Neprilysin inhibition may augment vasodilators, such as bradykinin. We hypothesized that bradykinin contributes to blood pressure (BP) lowering with sacubitril/valsartan in stable ambulatory patients with heart failure and reduced ejection fraction <50%. METHODS: In a randomized, double-blind crossover trial, participants received intravenous infusion of the bradykinin B2 receptor inhibitor icatibant and a matching placebo for 6 hours following sacubitril/valsartan dosing at acute initiation (n=36) and after 8 weeks of chronic therapy (n=30). The primary end point was maximal change in mean arterial pressure (MAP). Plasma natriuretic peptides, urine cyclic GMP, urine volume, sodium excretion, renal plasma flow, and renovascular resistance were measured. RESULTS: The first dose of sacubitril/valsartan (50 mg) significantly lowered MAP by a mean maximum of ≈10 mm Hg, which was similar during icatibant and placebo. Within 6 hours after the first sacubitril/valsartan dose, plasma ANP (atrial natriuretic peptide [1-28]) and urine cGMP/creatinine increased significantly, whereas B-type NP (1-32) and NT-proBNP (N-terminal pro B-type natriuretic peptide) did not. Icatibant partially blunted the rise in urine cGMP/creatinine, but did not affect other parameters. After 8 weeks of sacubitril/valsartan titrated to maximally tolerated doses, baseline ANP (1-28) remained increased, and baseline MAP and NT-proBNP were decreased compared with before sacubitril/valsartan initiation. MAP decreased further after dose administration of sacubitril/valsartan, and the mean maximal reduction in MAP was significantly attenuated during icatibant compared with placebo (9 versus 12 mm Hg; =0.013). Icatibant also decreased renal plasma flow and increased renal vascular resistance after chronic dosing, without affecting heart rate, urine volume, urine sodium, cGMP/creatinine, or natriuretic peptides. CONCLUSIONS: BP lowering with sacubitril/valsartan occurs with both acute and chronic dosing. ANP (1-28) appears to mediate the initial BP reduction, whereas bradykinin contributes to BP lowering after dosing during chronic therapy. Clarifying these mechanisms may inform clinical management to optimize the benefit of this important heart failure and reduced ejection fraction therapy. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT04113109.
Mavacamten Versus Alcohol Septal Ablation in Obstructive Hypertrophic Cardiomyopathy: An Echocardiography-Derived Pressure-Volume Analysis.
Reil JC, Sequeira V, Coppée C … +8 more , Peters K, Federspiel JM, Steendijk P, Maack C, Waddingham MT, Rudolph V, Reil GH, Scholtz S
Circ Heart Fail · 2026 May · PMID 41969098 · Publisher ↗
BACKGROUND: Obstructive hypertrophic cardiomyopathy (oHCM) is characterized by left ventricular (LV) outflow tract obstruction, which increases afterload and chronically activates the Anrep response, a compensatory (afte...
BACKGROUND: Obstructive hypertrophic cardiomyopathy (oHCM) is characterized by left ventricular (LV) outflow tract obstruction, which increases afterload and chronically activates the Anrep response, a compensatory (afterload-driven) state of hyperdynamic systole, prolonged systolic ejection time, and increased myocardial workload. We investigated whether the myosin inhibitor mavacamten reverses this state, comparing its effects to the anatomic relief achieved by alcohol septal ablation. METHODS: Thirty-six patients with symptomatic oHCM were treated with mavacamten. Of these, 29 who achieved a resting LV outflow tract gradient <50 mm Hg at 3 months (responders) underwent echocardiography-derived pressure-volume analysis before and after therapy. For comparison, a separate cohort of 13 patients with oHCM underwent identical pressure-volume analysis before and 3 months post-alcohol septal ablation. Anrep-related indices were quantified: afterload (LV end-systolic pressure [LVESP] and effective arterial elastance [Ea]), contractility (end-systolic elastance [Ees] and end-systolic volume at 150 mm Hg [ESV]), and systolic ejection time. Myocardial workload (stroke work, potential energy, and pressure-volume area) and diastolic function (LV end-diastolic pressure [LVEDP], end-diastolic volume [EDV], and volume at an LVEDP of 15 mm Hg [V]) were also assessed. RESULTS: At baseline, all patients showed chronic activation of the Anrep response: elevated afterload (high LVESP and Ea), hypercontractility (high Ees and low ESV), and prolonged systolic ejection time, accompanied by increased mechanical workload (elevated stroke work, potential energy, and pressure-volume area). After 3 months, both mavacamten responders and alcohol septal ablation responders showed comparable ventricular unloading: reductions in afterload and contractility, shortened systolic ejection time, and decreased myocardial workload, all while preserving stroke volume. Diastolic indices improved (increased EDV and V, and decreased LVEDP). Conversely, in mavacamten nonresponders (persistent LV outflow tract gradient ≥50 mm Hg at 3 months), Anrep-related indices and myocardial workload did not change. CONCLUSIONS: In oHCM, chronic Anrep activation maintains cardiac output against elevated afterload at high energetic cost. Our finding that mavacamten and alcohol septal ablation produce comparable hemodynamic corrections establishes the reversal of this afterload-driven state as a central mechanistic target of therapy in oHCM.
Prognostic Factors for Long-Term Risk of Stroke After Transient Ischemic Attack or Minor Stroke: A Systematic Review and Meta-Analysis.
Khan F, Yogendrakumar V, Lun R … +25 more , Marx CE, Rochwerg B, Tran A, Fernando SM, Ganesh A, Barber PA, Ögren J, Ois A, Giralt-Steinhauer E, Khanevski AN, Leng X, Tian X, Leung TW, Verburgt E, Verhoeven J, de Leeuw FE, Ildstad F, Fandler-Höfler S, Aarnio K, von Sarnowski B, Lorenzetti DL, Coutts SB, Amarenco P, Hankey GJ, Hill MD
Circulation · 2026 Apr · PMID 41849763 · Publisher ↗
BACKGROUND: Patients with a transient ischemic attack (TIA) or minor stroke have an increased risk of subsequent stroke that persists for at least 10 years. We aimed to identify prognostic factors associated with long-te...
BACKGROUND: Patients with a transient ischemic attack (TIA) or minor stroke have an increased risk of subsequent stroke that persists for at least 10 years. We aimed to identify prognostic factors associated with long-term risk of stroke in this patient group and estimate their population attributable fraction (PAF). METHODS: A systematic review was performed of MEDLINE, Embase, and Web of Science for cohort studies including patients with TIA or minor stroke that evaluated factors for subsequent stroke over a follow-up period of ≥1 year. We pooled hazard ratios adjusted for relevant confounders using random-effect meta-analysis and determined the PAF of factors based on their pooled prevalence and adjusted hazard ratio. We assessed certainty of evidence using the grading of recommendations, assessment, development, and evaluation approach. The study is registered in PROSPERO (CRD42023476551). RESULTS: From 14 732 identified citations, we included 28 cohort studies comprising 86 810 patients with TIA or minor stroke (median age, 69 years [interquartile range, 65-71]; 52%-60% male patients). Factors that had high certainty evidence of association with increased long-term risk of stroke included older age (adjusted hazard ratio, 1.04 per year increase [95% CI, 1.02-1.05]); male sex (1.25, 1.15-1.36; PAF 13.0% [95% CI, 7.8-18.7]); atrial fibrillation (1.34, 1.18-1.52; 3.8% [95% CI, 0.3-9.9]); diabetes (1.52, 1.32-1.75; 7.7%, 3.1-14.1); hypertension (1.60, 1.31-1.94; 19.3%, 8.4-31.6); ischemic heart disease (1.67, 1.28-2.18; 10.7%, 2.8-22.9); history of stroke or TIA before the index event (1.70, 1.43-2.02; 12.0%, 5.2-21.4); smoking (1.29, 1.05-1.60; 11.2%, 1.0-30.7); ABCD (age, blood pressure, clinical features, duration of TIA, and presence of diabetes) score of ≥4 (1.59, 1.31-1.94; 18.0%, 2.9-39.9); presence of acute infarct on neuroimaging (1.97, 1.41-2.74; 19.0%, 5.2-38.9), including diffusion-weighted imaging-positive lesions (1.86, 1.02-3.37; 14.0%, 7.0-25.0); minor stroke as index event (1.75, 1.35-2.27 versus TIA; 28.0%, 10.2-47.6); presentation with aphasia or dysarthria (1.45, 1.24-1.69; 19.2%, 0.2-53.1); presentation with paresis (1.45, 1.15-1.84; 22.0%, 3.8-43.4); and etiologic stroke subtypes, including cardioembolism (2.16, 1.53-3.05; 14.6%, 3.1-33.5), large-artery atherosclerosis (2.19, 1.68-2.86; 13.2%, 5.1-25.5), and small-vessel disease (1.69, 1.14-2.49; 16.8%, 5.0-34.3). CONCLUSIONS: These findings can help identify patients with a particularly enduring risk of stroke who are most likely to benefit from ongoing monitoring and treatment and facilitate the development and implementation of targeted stroke prevention strategies.
Apolipoprotein D, a Novel Ligand for CD36, Is Essential for Blood-Brain Barrier Integrity.
Gong CX, Shi PX, Huang YJ … +30 more , Dai Y, Hu LL, Cheng XF, Zhang S, He MT, Wang JH, Meng ZY, Fang YL, Wang BQ, Zhao Y, He CK, Yang GQ, Zi WJ, Qiu ZM, Li FL, Lin S, Lu H, Zhao CH, Zhang C, Liu ZY, Dong MQ, Ouyang Q, Zheng HT, Niu JQ, Mei F, Sun BL, Zhou J, Xie Q, Li FF, Yang QW
Circulation · 2026 Apr · PMID 41645912 · Full text
BACKGROUND: The disruption of the blood-brain barrier (BBB) is a central pathogenic event in many central nervous system disorders. However, the mechanisms regulating BBB function remain incompletely understood, and effe...
BACKGROUND: The disruption of the blood-brain barrier (BBB) is a central pathogenic event in many central nervous system disorders. However, the mechanisms regulating BBB function remain incompletely understood, and effective treatments are lacking. Brain mural cells differ significantly from their peripheral counterparts, a distinction likely critical for maintaining BBB integrity. METHODS: We combined proteomic profiling of human brain peripheral mural cells with multiple ischemic stroke models (global apolipoprotein D [ApoD] knockout, mural cell-specific ApoD knockout, and adeno-associated virus-mediated ApoD overexpression) to evaluate the role of ApoD in BBB integrity. Mechanistic studies (co-immunoprecipitation, binding assays, including surface plasmon resonance, bio-layer interferometry, cross-linking mass spectrometry, and CD36 loss-of-function approaches, both in vitro and in vivo) were performed to determine how ApoD interacts with CD36 and inhibits its signaling. Finally, we assessed the effect of ApoD glycosylation on CD36 binding and tested therapeutic delivery of hypoglycosylated ApoD in stroke. RESULTS: Our study has shown an increased expression of ApoD in mural cells after ischemic stroke. We found that mural cell-derived ApoD functions as an inhibitory ligand of endothelial CD36, suppressing pathological endothelial proliferation, preserving BBB integrity, and promoting neurological recovery. Additionally, overexpression of ApoD in mural cells improved BBB integrity and enhanced functional recovery in -null mice. Mechanistically, ApoD competes with long-chain fatty acids for CD36 binding and directly attenuates downstream CD36 signaling. Furthermore, we reveal that peripheral hyperglycosylated ApoD (hyperglyco-ApoD) showed minimal effect on BBB integrity maintenance, whereas hypoglycosylation of ApoD enhances its binding affinity to CD36, amplifying its therapeutic efficacy. Exogenous administration of hypoglyco-ApoD via vein injection profoundly inhibited BBB disruption and improved neural function, especially in aging stroke. CONCLUSIONS: Our work identifies a previously unrecognized paracrine mechanism in which mural cell-derived ApoD directly engages endothelial CD36 to restrain pathological endothelial proliferation, thereby preserving BBB integrity and promoting neurological recovery after stroke. These findings further suggest that hypoglycosylated ApoD, with its higher CD36-binding affinity, merits investigation as a potential strategy to enhance BBB repair in central nervous system disorders.
Finerenone, Liver Biomarkers, and Heart Failure With Mildly Reduced/Preserved Ejection Fraction: An Analysis of FINEARTS-HF.
Butt JH, Henderson AD, Jhund PS … +21 more , Claggett BL, Desai AS, Borentain M, Rohwedder K, Dayoub R, De Sanctis Y, Lam CSP, Senni M, Shah SJ, Voors AA, Bauersachs J, Fonseca C, Linssen GCM, Petrie MC, Schou M, Verma S, Zannad F, Pitt B, Vaduganathan M, Solomon SD, McMurray JJV
Circ Heart Fail · 2026 Feb · PMID 41608790 · Publisher ↗
BACKGROUND: The prevalence and prognostic significance of liver biomarkers in heart failure (HF) with mildly reduced or preserved ejection fraction are uncertain, with both potential hemodynamic and metabolic contributio...
BACKGROUND: The prevalence and prognostic significance of liver biomarkers in heart failure (HF) with mildly reduced or preserved ejection fraction are uncertain, with both potential hemodynamic and metabolic contributions to liver dysfunction in these patients. We evaluated the prevalence and prognostic value of liver biomarkers and assessed the effects of the nonsteroidal mineralocorticoid receptor antagonist finerenone on these biomarkers and clinical outcomes in FINEARTS-HF (Finerenone Trial to Investigate Efficacy and Safety Superior to Placebo in Patients With Heart Failure). METHODS: FINEARTS-HF was a randomized, double-blind, placebo-controlled trial that enrolled 6001 patients with left ventricular ejection fraction ≥40%, evidence of structural heart disease, and elevated NT-proBNP (N-terminal pro-B-type natriuretic peptide) levels. Liver biomarkers examined were total bilirubin, alkaline phosphatase, alanine aminotransferase, and aspartate aminotransferase. RESULTS: Among 5873 patients with available baseline bilirubin measurements, 11.9% had elevated levels (>1.0 mg/dL). Higher bilirubin levels were associated with a greater risk of total worsening HF events and cardiovascular death. Compared with placebo, finerenone rapidly reduced bilirubin and alkaline phosphatase levels (but not transaminase levels), with effects sustained over time. Finerenone reduced the risk of total worsening HF events and cardiovascular death across all bilirubin tertiles (T1 [<0.4 mg/dL], rate ratio 0.94 [95% CI, 0.75-1.17]; T2 [0.5-0.6 mg/dL], 0.83 [0.66-1.05]; T3 [≥0.7 mg/dL], 0.77 [0.62-0.97]), with no significant interaction by bilirubin level (=0.43). Consistent effects were observed for the components of the primary outcome, all-cause death, and improvement in the Kansas City Cardiomyopathy Questionnaire total symptom score. CONCLUSIONS: Baseline bilirubin concentration was an independent predictor of worse outcomes but did not modify the benefits of finerenone on morbidity and mortality in HF with mildly reduced or preserved ejection fraction. Finerenone reduced bilirubin and alkaline phosphatase, suggesting a possible decongestive effect in HF with mildly reduced or preserved ejection fraction. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT04435626.
Genetic Architecture of N-Terminal Pro-B-Type Natriuretic Peptide in a Multiancestry Study Population.
Shetty NS, Pampana A, Gaonkar M … +22 more , Nayak A, Bal HS, Patel N, Vekariya N, Smith JG, Morrison AC, Yu B, Psaty BM, Boerwinkle E, Floyd JS, Rotter JI, Taylor KD, Lange LA, Irvin MR, Cushman M, Rich SS, Vasan RS, Wang TJ, Guo X, Li P, Arora G, Arora P
Circ Genom Precis Med · 2026 Feb · PMID 41603044 · Full text
BACKGROUND: NPs (natriuretic peptides) are bioactive hormones crucial for regulating blood pressure, glucose homeostasis, and lipid metabolism. Despite the high heritability of circulating NP levels, the genetic determin...
BACKGROUND: NPs (natriuretic peptides) are bioactive hormones crucial for regulating blood pressure, glucose homeostasis, and lipid metabolism. Despite the high heritability of circulating NP levels, the genetic determinants of NP regulation, particularly across ancestries and sexes, remain poorly understood. The objective of the current study was to identify genetic variants associated with NT-proBNP (N-terminal pro-B-type NP) levels in a multiancestry study population. METHODS: Whole genome sequencing and array-based data from 81 213 individuals without heart failure were analyzed from the Trans-Omics for Precision Medicine cohorts, UK Biobank, All of Us Research Program, and REGARDS (Reasons for Geographic and Racial Differences in Stroke) study to identify common, rare, and structural variants associated with NT-proBNP levels. The main outcome of the study was rank-based inverse normal and standardized NT-proBNP levels. Genetic associations with NT-proBNP were examined, followed by gene prioritization, transcriptome-wide association studies, colocalization, and rare variant analyses. RESULTS: Nine novel loci and 3 previously reported loci were identified to be associated with NT-proBNP levels. Novel structural variants were detected across 12 loci. Similar effect sizes were observed for both common and rare variants. Key genes such as (10q26.11) and (4q24) were identified through gene prioritization, with prior animal models supporting their therapeutic relevance. Rare variant analysis identified 6 masks with significant associations, specifically non-coding masks, suggesting regulatory modulation of NT-proBNP. CONCLUSIONS: This study identifies novel common, rare, and structural variants associated with NT-proBNP levels, highlighting the contribution of both coding and regulatory non-coding variation. These findings advance our understanding of the genetic architecture of NT-proBNP and may inform future cardiometabolic therapeutic strategies.
2026 Heart Disease and Stroke Statistics: A Report of US and Global Data From the American Heart Association.
Palaniappan LP, Allen NB, Almarzooq ZI … +45 more , Anderson CAM, Arora P, Avery CL, Baker-Smith CM, Bansal N, Currie ME, Earlie RS, Fan W, Fetterman JL, Barone Gibbs B, Heard DG, Hiremath S, Hong H, Hyacinth HI, Ibeh C, Jiang T, Johansen MC, Kazi DS, Ko D, Kwan TW, Leppert MH, Li Y, Magnani JW, Martin KA, Martin SS, Michos ED, Mussolino ME, Ogungbe O, Parikh NI, Perez MV, Perman SM, Sarraju A, Shah NS, Springer MV, St-Onge MP, Thacker EL, Tierney S, Urbut SM, Van Spall HGC, Voeks JH, Whelton SP, Wong SS, Zhao J, Khan SS, American Heart Association Council on Epidemiology and Prevention Statistics Committee and Stroke Statistics Committee
Circulation · 2026 Mar · PMID 41562125 · Publisher ↗
BACKGROUND: The American Heart Association annually reports the most up-to-date statistics related to heart disease, stroke, and cardiovascular risk factors, including core health behaviors (smoking, physical activity, n...
BACKGROUND: The American Heart Association annually reports the most up-to-date statistics related to heart disease, stroke, and cardiovascular risk factors, including core health behaviors (smoking, physical activity, nutrition, sleep, and obesity) and health factors (cholesterol, blood pressure, glucose control, and cardiovascular-kidney-metabolic syndrome) that contribute to cardiovascular health. The 2026 Heart Disease and Stroke Statistics Update presents the latest data on a range of major clinical heart and circulatory disease conditions (including stroke, brain health, complications of pregnancy, kidney disease, congenital heart disease, rhythm disorders, sudden cardiac arrest, subclinical atherosclerosis, coronary heart disease, cardiomyopathy, heart failure, valvular disease, venous thromboembolism, and peripheral artery disease) and the associated outcomes (including quality of care, procedures, and economic costs). METHODS: The American Heart Association, through its Epidemiology and Prevention Statistics Committee, continuously monitors and evaluates sources of data on heart disease and stroke in the United States and globally to provide the most current information available in the annual Statistics Update with review of published literature through the year before writing. The 2026 Statistics Update is the product of a full year's worth of effort in 2025 by dedicated volunteer clinicians and scientists, committed government professionals, and American Heart Association staff members. This year's edition includes a new chapter on cardiovascular-kidney-metabolic syndrome, as well as an expanded chapter on tobacco and nicotine use and exposure. RESULTS: Each of the chapters in the Statistics Update focuses on a different topic related to heart disease and stroke statistics. CONCLUSIONS: The Statistics Update represents a critical resource for the lay public, policymakers, media professionals, clinicians, health care administrators, researchers, health advocates, and others seeking the best available data on these factors and conditions.
Impact of Pregnancy on Mortality in Dilated Cardiomyopathy: Immediate and 12-Month Postpartum Outcomes: Data From the InCor Pregnancy and Heart Disease Registry.
Avila MS, Bacal F, Fernandes F … +2 more , Tarasoutchi F, Avila WS
Circ Heart Fail · 2026 May · PMID 41492777 · Publisher ↗
BACKGROUND: Pregnant women with dilated cardiomyopathy (DCM) face high risks of complications and maternal death due to hemodynamic overload, withdrawal of teratogenic but essential therapies, and limited treatment optio...
BACKGROUND: Pregnant women with dilated cardiomyopathy (DCM) face high risks of complications and maternal death due to hemodynamic overload, withdrawal of teratogenic but essential therapies, and limited treatment options during pregnancy. To evaluate maternal and fetal outcomes in women with DCM during pregnancy and up to 12 months postpartum, across different etiologies, and identify predictors of maternal death. METHODS: Prospective cohort of pregnant women with confirmed DCM enrolled in the InCor Pregnancy and Heart Disease Registry. All received standardized cardio-obstetric care. Left ventricular ejection fraction was assessed by echocardiography; brain natriuretic peptide was evaluated when available. Treatment during pregnancy included β-blockers, hydralazine, diuretics, nitrates, enoxaparin, and hospitalization when needed. Guideline-directed therapy was resumed postpartum. Outcomes included maternal (heart failure, arrhythmias, thromboembolism, death) and obstetric/fetal complications. Logistic regression identified predictors of maternal mortality. RESULTS: Among 983 registry patients (2013-2023), 90 had DCM. Causes were peripartum (32), idiopathic (21), myocarditis (15), Chagas disease (11), and others (11). Maternal complications occurred in 51.1% during pregnancy, 36.0% in the early postpartum period (up to 6 weeks after delivery), and 38.6% in the late postpartum period (from 6 weeks to 12 months after delivery). All 9 maternal deaths (10%) occurred postpartum-mostly due to heart failure-at a mean of 8.8±3.1 months. Cesarean section was performed in 75%, with 10% fetal loss and 33.8% prematurity. Mean birth weight was 2606 g. Left ventricular ejection fraction improved from 32% at diagnosis to 39% during pregnancy and 42% at 12 months. Lower left ventricular ejection fraction (odds ratio, 0.87; =0.006) and prior thromboembolism (odds ratio, 15.5; =0.017) were independent predictors of death. CONCLUSIONS: Pregnancy in women with DCM was associated with high morbidity and late mortality. Reduced left ventricular ejection fraction and a history of thromboembolism were independent predictors of maternal death.
Rare Variants in HTRA1, SGTB, and RBM12 Confer Risk of Atherosclerotic Cardiovascular Disease Independent of Traditional Cardiovascular Risk Factors.
Lockhart SM, Puri A, Zhao Y … +9 more , Saudek V, Gardner EJ, Kentistou KA, Lam BYH, Day FR, O'Rahilly S, Perry JRB, Ong KK, Jackrel ME
Circ Genom Precis Med · 2025 Dec · PMID 41190437 · Full text
BACKGROUND: Atherosclerosis is a pathophysiological process common to a range of cardiovascular diseases. We reasoned that considering clinical presentations of atherosclerosis across the coronary, peripheral, and cerebr...
BACKGROUND: Atherosclerosis is a pathophysiological process common to a range of cardiovascular diseases. We reasoned that considering clinical presentations of atherosclerosis across the coronary, peripheral, and cerebrovasculature as a single entity would enhance statistical power to identify rare genetic variation driving pathological processes across multiple vascular beds. METHODS: We performed an exome-wide association study of atherosclerotic cardiovascular disease in 434 438 UK Biobank participants of European ancestry. RESULTS: We identified rare, predicted damaging variants in HTRA1, SGTB, and RBM12 to be associated with risk of atherosclerotic cardiovascular disease, independent of known risk factors. Both SGTB and HTRA1 were downregulated in the aorta of patients with coronary artery disease compared with controls. Loss-of-function variants in the RNA-binding protein RBM12 increased the risk of coronary, cerebrovascular, and peripheral vascular diseases to a similar extent. SGTB increased the risk of atherosclerotic cardiovascular disease in the coronary and peripheral circulations but not the cerebrovasculature. While loss-of-function variants in HTRA1 are known to cause monogenic stroke syndromes, we found that damaging missense variants in HTRA1 are associated with increased risk of disease in both the cerebrovascular and coronary circulation. Surprisingly, the increased risk of coronary artery disease was driven predominantly by a single missense variant (p.R227W; minor allele frequency, 0.009). In vitro, the R227W mutant HTRA1 efficiently proteolyzed the disordered substrate casein but not aggregated α-synuclein. In contrast, a stroke risk-raising variant (D320N) could not efficiently process any of the tested substrates. CONCLUSIONS: We identified novel genetic variants predisposing to atherosclerotic cardiovascular diseases that act independently of established cardiovascular risk factors. The observed phenotypic and functional heterogeneities between HTRA1 variants suggest that distinct biochemical mechanisms drive HTRA1-related vascular disease in the brain and heart.
Prognostic Value of Natriuretic Peptide Levels in Heart Failure With Recovered Ejection Fraction.
Kodur N, Gunsalus P, Milinovich A … +2 more , Dalton JE, Tang WHW
Circ Heart Fail · 2025 Nov · PMID 41178541 · Publisher ↗
BACKGROUND: There are currently no robust clinical markers for assessing prognosis in patients with heart failure (HF) with recovered left ventricular ejection fraction (LVEF). This study sought to investigate whether NT...
BACKGROUND: There are currently no robust clinical markers for assessing prognosis in patients with heart failure (HF) with recovered left ventricular ejection fraction (LVEF). This study sought to investigate whether NT-proBNP (N-terminal pro-B-type natriuretic peptide) measured at the time of LVEF recovery is an independent predictor of prognosis among patients with HF with recovered LVEF. METHODS: This retrospective cohort study (2009-2024) included 3935 patients with HF with recovered LVEF (previous LVEF of ≤40% with subsequent improvement to ≥50%) and available NT-proBNP data at the time of LVEF recovery. Patients were categorized into 7 different NT-proBNP groups, which were compared using Kaplan-Meier analysis and multivariable Cox regression to evaluate the outcome of LVEF relapse (decrease in LVEF by ≥10% to <50%) and the composite outcome of HF hospitalization or all-cause death. RESULTS: The median value of NT-proBNP at the time of LVEF recovery was 1341 pg/mL (interquartile range, 400-4207). The probability of remaining free from LVEF relapse and the composite outcome decreased across NT-proBNP groups. After multivariable adjustment, NT-proBNP was an independent predictor of both LVEF relapse and the composite outcome, with higher NT-proBNP levels associated with higher risk of both outcomes in a dose-response manner. Even near-normal NT-proBNP levels (125-299 pg/mL) were associated with poorer prognosis relative to normal levels (<125 pg/mL), with a 46% higher risk of LVEF relapse and 82% higher risk of the composite outcome. This relationship was consistent and similar across age, sex, atrial fibrillation status, and renal function, but was modified by body mass index, with higher body mass index associated with higher risk. Notably, NT-proBNP was predictive of the composite outcome even when patients sustained LVEF recovery without experiencing LVEF relapse. CONCLUSIONS: NT-proBNP is an independent and robust predictor of prognosis in patients with HF with recovered LVEF and may therefore be used to guide further optimization of pharmacotherapy.
Heart Stress and Blood Pressure Management in Older Adults: Post Hoc Analysis of the ASPREE Trial.
Cai A, Bayes-Genis A, Ryan J … +18 more , Feng Y, Januzzi JL, Tonkin AM, Zheng J, Nelson MR, Neumann JT, Woods RL, Tran C, Schutte AE, Pandey A, Chen LY, Liu L, Zhang J, McNeil JJ, Beilin L, Tes HF, Parati G, Zhou Z
Circulation · 2025 Dec · PMID 41122849 · Full text
BACKGROUND: Blood pressure (BP) management in older adults is complex because of age-related physiological changes and uncertainty around ideal systolic BP (SBP) targets. Heart stress (HS), defined by age-adjusted elevat...
BACKGROUND: Blood pressure (BP) management in older adults is complex because of age-related physiological changes and uncertainty around ideal systolic BP (SBP) targets. Heart stress (HS), defined by age-adjusted elevation in NT-proBNP (N-terminal pro-B-type natriuretic peptide) levels, may improve cardiovascular disease (CVD) risk stratification and support more individualized BP management. METHODS: We conducted a post hoc analysis of ASPREE (Aspirin in Reducing Events in the Elderly) involving 11 941 community-dwelling older adults without CVD at enrollment (mean age, 75.1 years; 53.5% women). HS was defined by NT-proBNP ≥150 pg/mL for participants 65 to 74 years of age and ≥300 pg/mL for participants ≥75 years of age. Participants were categorized into 4 groups by hypertension and HS status. The primary outcome was total CVD events (a composite of nonfatal myocardial infarction, fatal or nonfatal stroke, coronary heart disease death, or hospitalization for heart failure). Associations between hypertension and SBP with total CVD events were examined by HS status using Cox proportional-hazards models and restricted cubic spline. SBP was evaluated categorically (<120, 120-129, 130-139, 140-159, or ≥160 mm Hg) and continuously. A landmark sensitivity analysis excluded participants with CVD events or censoring in the first 2 years, with follow-up starting at year 3. RESULTS: HS was present in 25.8% of participants. Compared with the reference group (no hypertension or HS), adjusted hazard ratios (95% CI) for total CVD events were 1.41 (1.18-1.70) for hypertension + no HS, 1.79 (1.34-2.39) for no hypertension + HS, and 2.32 (1.89-2.84) for hypertension + HS (<0.001). Among participants without HS, the lowest incidence of total CVD events occurred at SBP 130 to 139 mm Hg, showing a U-shaped association across SBP levels (=0.011). Among participants with HS, risk increased linearly with SBP ( =0.85) and was lowest at SBP <120 mm Hg. Landmark analyses yielded generally consistent findings. CONCLUSIONS: HS is common in older adults and jointly associated with hypertension and increased CVD risk. The SBP-CVD relationship differs by HS status, suggesting a potential value of HS for guiding individualized BP management. Prospective studies are warranted to determine whether HS-guided strategies improve BP control and reduce CVD risk in older adults.
Bailout Intracranial Angioplasty or Stenting After Thrombectomy for Acute Large Vessel Occlusion: 1-Year Outcomes of ANGEL-REBOOT.
Gao F, Tong X, Wei M … +53 more , Yao X, Li L, Pan Y, Jia B, Nguyen TN, Yang M, Sun D, Feng G, Yuan G, Xu C, Yuan Z, Wan Y, Wang J, Jing P, Yang X, Wu Z, Hu W, Jiang Y, Wang C, Wen C, Tang J, Luo X, Wu Y, Shen R, Zheng T, Sun Y, Chang M, Liu Y, Haihua Y, Li D, Yin B, Jia W, Wan D, Xu G, Guo Z, Sun D, Wang Y, Duan J, Wang L, Wang G, Wei L, Ma G, Huo X, Mo D, Ma N, Ren Z, Liu L, Zhao X, Wang Y, Fiehler J, Wang Y, Miao Z, ANGEL-REBOOT Study Group
Circulation · 2025 Nov · PMID 41122847 · Publisher ↗
BACKGROUND: The long-term benefits of bailout intracranial angioplasty or stenting (BAOS) after thrombectomy in patients with acute large vessel occlusion remain unclear. This study compared BAOS with standard therapy in...
BACKGROUND: The long-term benefits of bailout intracranial angioplasty or stenting (BAOS) after thrombectomy in patients with acute large vessel occlusion remain unclear. This study compared BAOS with standard therapy in patients with large vessel occlusion with unsuccessful recanalization (expanded Thrombolysis In Cerebral Infarction score 0-2a) or >70% residual stenosis after thrombectomy. METHODS: ANGEL-REBOOT (Randomized Study of Bailout Intracranial Angioplasty Following Thrombectomy for Acute Large Vessel Occlusion) was a multicenter, open-label, blinded-end point, randomized trial conducted across 36 Chinese hospitals. Patients ≥18 years of age with anterior or posterior circulation large vessel occlusion within 24 hours of stroke onset were enrolled. After identification of thrombectomy failure or high-grade residual stenosis, patients were randomly assigned to the BAOS group (intervention) or the standard therapy group (control), in which thrombectomy was continued or terminated. The use of tirofiban was permitted in both groups during and after the procedure. In the intention-to-treat population, the primary outcome was analyzed using an assumption-free ordinal analysis (Wilcoxon-Mann-Whitney test) to compare the modified Rankin Scale scores (ordinal variable ranging from 0 to 6) between groups at 1-year follow-up, from which the generalized odds ratio was derived. Secondary outcomes included stroke recurrence in the treated artery and all-cause mortality within 1 year, analyzed using Cox proportional hazards models. RESULTS: A total of 348 patients were randomly assigned (176 to the BAOS group and 172 to the standard therapy group) and followed for 90 days, from December 19, 2021, to June 2, 2023. Of these, 326 patients (166 in the BAOS group and 160 in the standard therapy group) completed the 1-year follow-up. Compared with standard therapy, BAOS significantly improved the 1-year modified Rankin Scale score distribution (generalized odds ratio, 1.34 [95% CI, 1.05-1.73]; =0.02). Fewer stroke recurrences in the treated artery occurred in the BAOS group than in the standard therapy group (7 of 166 [4%] versus 21 of 160 [13%]; hazard ratio, 0.30 [95% CI, 0.13-0.71]; =0.006). One-year mortality rates were similar between groups (25 of 166 [15%] versus 27 of 160 [17%]; hazard ratio, 0.87 [95% CI, 0.50-1.50]). CONCLUSIONS: Among Chinese patients with large vessel occlusion with unsuccessful recanalization or high-grade residual stenosis after thrombectomy, BAOS was associated with reduced disability and stroke recurrence after 1 year compared with standard therapy. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT05122286.
Association of Component Strategies of the Target Stroke Phase 3 Nationwide Quality Improvement Program With Accelerated Door-to-Puncture and Door-In-Door-Out Times for Ischemic Stroke Endovascular Thrombectomy in the United States.
Mac Grory B, Asif KS, Xu H … +23 more , Alhanti B, B Lusk J, Hasan D, Park S, Boehme AK, Zachrison KS, Goyal M, Southerland AM, Jadhav A, Ortega Gutierrez S, Hassan A, Fargen K, Sheth KN, Jauch EC, Xian Y, Peterson ED, Smith EE, Messe SR, Schwamm LH, Panagos P, Wira C, Saver JL, Fonarow GC
Circ Cardiovasc Qual Outcomes · 2025 Nov · PMID 41111412 · Full text
BACKGROUND: The Target Stroke Phase III program is a national quality improvement initiative led by the American Heart Association, which sought to improve the quality of care for patients with acute stroke undergoing ac...
BACKGROUND: The Target Stroke Phase III program is a national quality improvement initiative led by the American Heart Association, which sought to improve the quality of care for patients with acute stroke undergoing acute reperfusion therapy including endovascular thrombectomy (EVT). METHODS: A retrospective, observational cohort study was performed using data from the American Heart Association Get With The Guidelines-Stroke Program between January 1, 2017, and March 31, 2022. Three categories of patients were analyzed: (1) patients who arrived directly at the thrombectomy hospital and had EVT, (2) patients who were transferred in from a nonthrombectomy hospital and had EVT, and (3) patients at a nonthrombectomy hospital who were potentially eligible for EVT, received intravenous thrombolysis, and were transferred out. The primary end point of this study for thrombectomy hospitals was door-to-puncture time. RESULTS: In direct-arriving EVT patients, 2 Target Stroke Phase III strategies were independently associated with shorter door-to-puncture time: (1) alerting the neurointerventional team based on emergency medical services prenotification (-21.9 [95% CI, -42.5 to -1.3] minutes) and (2) performance of a brain computed tomography and computed tomography angiography in all patients presenting ≤24 hours from time last known well (-6.6 [95% CI, -11.8 to -1.5] minutes). In transfer-in EVT patients, 2 Target Stroke Phase III strategies were independently associated with a shorter door-to-puncture time: (1) increased use of stroke screening tools (-3.5 [95% CI, -6.4 to -0.6] minutes per 25% increase in use of the screening tool) and (2) increased use of a camera during telestroke consultations (-5.8 [95% CI, -10.7 to -0.9] minutes per 25% increase in camera use). CONCLUSIONS: Several Target Stroke Phase III strategies are associated with more timely care, which are distinctly different for thrombectomy and nonthrombectomy hospitals and for patients arriving by emergency medical services compared with interfacility transfer.
Impact of Cerebral Embolic Protection on Cognitive Function After Transcatheter Aortic Valve Implantation: Data From the BHF PROTECT-TAVI Randomized Trial.
Kennedy J, Blackman DJ, Dodd M … +8 more , Poggesi A, Read L, Jamal Z, Evans R, Clayton T, Kharbanda RK, Hildick-Smith D, BHF PROTECT-TAVI Investigators
Circulation · 2025 Nov · PMID 40884786 · Full text
BACKGROUND: In addition to the risk of stroke, patients undergoing transcatheter aortic valve implantation (TAVI) are susceptible to a decline of neurocognitive function. This may occur because of embolization of materia...
BACKGROUND: In addition to the risk of stroke, patients undergoing transcatheter aortic valve implantation (TAVI) are susceptible to a decline of neurocognitive function. This may occur because of embolization of material (eg, valve or calcium) to the brain. Cerebral embolic protection (CEP) devices are engineered to capture this debris, potentially mitigating its incidence. METHODS: This is a secondary analysis of the BHF PROTECT-TAVI trial (British Heart Foundation Randomized Trial of Routine Cerebral Embolic Protection in Transcatheter Aortic Valve Implantation), in which participants with aortic stenosis from across 33 centers in the United Kingdom were randomly assigned at a 1:1 ratio to undergo TAVI with a CEP device (SENTINEL, Boston Scientific; SENTINEL CEP group) or TAVI without a CEP device (control group). This analysis is restricted to those who underwent cognitive assessment. The primary outcome was the mean change in the telephone version of the Montreal Cognitive Assessment (t-MoCA) between baseline and 6 to 8 weeks after TAVI. The secondary outcome was a ≥3-point drop in total t-MoCA score between baseline and 6 to 8 weeks after TAVI. RESULTS: A total of 3535 participants, 1763 in the SENTINEL CEP group and 1772 in the control group (mean age 81.0 years, 37.7% women) randomized in BHF PROTECT-TAVI were included in the modified intention-to-treat population for this analysis. The median t-MoCA at presentation was 18 (interquartile range, 16-20). The median t-MoCA at 6 to 8 weeks was 20 (interquartile range, 17-21). The mean change in total t-MoCA score between baseline and 6 to 8 weeks adjusted for the baseline score was 0.83 (95% CI, 0.70-0.96) in the SENTINEL CEP group and 0.91 (95% CI, 0.79-1.04) in the control group. There was no difference in means between the treatment groups (-0.07 [95% CI, -0.22 to 0.09], =0.42). The incidence of a ≥3-point drop in the total t-MoCA score was 154 of 1763 (8.7%) in the SENTINEL CEP group and 142 of 1772 (8.0%) in the control group. The corresponding risk difference was 0.72% (95% CI, -1.10 to 2.55; =0.44). These findings were robust to sensitivity analyses. There was no evidence of an interaction between treatment assignment and any of the subgroups assessed. CONCLUSIONS: In the BHF PROTECT-TAVI trial, the use of CEP did not impact cognition after TAVI. REGISTRATION: URL: https://www.isrctn.com; Unique identifier: ISRCTN16665769.
Sacubitril/Valsartan and Prevention of Cardiac Dysfunction During Adjuvant Breast Cancer Therapy: The PRADA II Randomized Clinical Trial.
Omland T, Heck SL, Holte E … +10 more , Lilleaasen AM, Gynnild MN, Fagerland MW, Vinje-Jakobsen V, Næs AL, Blix ES, Larsen AI, Geisler J, Gulati G, Wethal T
Circulation · 2025 Oct · PMID 40884047 · Full text
BACKGROUND: Anthracycline- and trastuzumab-associated cardiotoxicity may lead to cardiac dysfunction and dose reduction or halt of potentially life-saving adjuvant cancer therapy. Whether angiotensin receptor/neprilysin...
BACKGROUND: Anthracycline- and trastuzumab-associated cardiotoxicity may lead to cardiac dysfunction and dose reduction or halt of potentially life-saving adjuvant cancer therapy. Whether angiotensin receptor/neprilysin inhibitors can prevent cancer therapy-related cardiac dysfunction and injury remains to be established. METHODS: PRADA II (Prevention of Cardiac Dysfunction During Adjuvant Breast Cancer Therapy) was a randomized, parallel-group, placebo-controlled, double-blind, multicenter trial conducted at 4 academic medical centers in Norway that evaluated the cardioprotective effect of sacubitril/valsartan versus placebo administered concomitantly with anthracycline-containing breast cancer therapy and continued for 18 months. The target dose was 97/103 mg BID. The primary outcome was change in left ventricular ejection fraction by cardiovascular magnetic resonance from prior to initiation of chemotherapy to 18 months thereafter. Secondary outcomes included change in echocardiographic global longitudinal strain, circulating cardiac troponins, and NT-proBNP (N-terminal pro-B-type natriuretic peptide). RESULTS: In total, 138 women (mean±SD age: 54.0±9.4 years) were randomized. The overall decline in left ventricular ejection fraction from baseline to 18 months was 2.2 percentage points (95% CI, 1.1 to 3.3) in the placebo group and 1.1 percentage points (95% CI, -0.01 to 2.2) in the sacubitril/valsartan group. The between-group difference was 1.1 percentage points (95% CI, -0.4 to 2.7; =0.16). Left ventricular global longitudinal strain was normal and remained stable in the sacubitril/valsartan group throughout the study (change from baseline to 18 months, -0.3 [95% CI, -0.80 to 0.2]). In contrast, there was a progressive decline in the placebo group (change from baseline to 18 months, 0.5 [95% CI, 0.05 to 1.0]). The between-group difference was -0.9 (95% CI, -1.5 to -0.2). The mean increases in NT-proBNP and cardiac troponin I concentrations from baseline to 18 months were greater in the placebo group than in the sacubitril/valsartan group (log difference, 0.3 [95% CI, 0.05 to 0.6] for NT-proBNP and 0.5 [95% CI, 0.1to 1.0] for cardiac troponin I). CONCLUSIONS: Anthracycline-based treatment for early breast cancer was associated with a reduction in left ventricular ejection fraction that was not significantly attenuated by sacubitril/valsartan. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03760588.
Feasibility, Reproducibility, and Prognostic Value of Exercise Echocardiography for Cardiac Output Reserve Assessment in Fontan Physiology.
Egbe AC, Abozied O, Abdelhalim AT … +4 more , ElZalabany S, Kholeif Z, Reddy YNV, Borlaug BA
Circ Heart Fail · 2025 Sep · PMID 40856614 · Full text
BACKGROUND: The purpose of this study was to assess the feasibility and prognostic value of cardiac output (CO) reserve assessment using exercise echocardiography in Fontan patients. We hypothesized that adults with Font...
BACKGROUND: The purpose of this study was to assess the feasibility and prognostic value of cardiac output (CO) reserve assessment using exercise echocardiography in Fontan patients. We hypothesized that adults with Fontan palliation had lower CO reserve compared with controls, and impaired CO reserve was associated with greater congestion (NT-proBNP [N-terminal pro-B-type natriuretic peptide]) and cardiovascular events (death/transplant/heart failure hospitalization) in Fontan patients. METHODS: Thirty-seven Fontan patients and 61 controls underwent exercise echocardiography using a supine cycle ergometer. Doppler-derived CO and oxygen consumption (VO) were assessed at rest and every stage of exercise. CO reserve was calculated as ∆CO/Watt (∆CO/W) and ∆CO/∆VO. RESULTS: Assessment of CO reserve was feasible in 95% of the Fontan group with modest reproducibility. Although both groups had similar CO at rest, the Fontan group had lower CO reserve with exercise as evidenced by lower ∆CO/W ratio (46±17 versus 57±19 mL/W; <0.001) and lower ∆CO/∆VO ratio (4.48±1.02 versus 5.37±2.18 mL/mL; =0.03). There was a correlation between ∆CO/W ratio and log NT-proBNP (r=0.65; <0.001), and between ∆CO/∆VO ratio and log NT-proBNP (r=0.53; =0.009). Impaired CO reserve was associated with congestion and cardiovascular events and provided improved prognostication (higher area under the curve and C statistics) above conventional echocardiographic indices and treadmill peak VO. CONCLUSIONS: Patients with Fontan palliation had lower CO reserve, and impaired CO reserve was associated with congestion and cardiovascular events. Further studies are required to determine whether cardiac interventions can improve CO reserve and whether changes in CO reserve can be used as a surrogate end point for therapeutic response.
Molecular Phenogroups in Heart Failure: Large-Scale Proteomics in a Population-Based Cohort.
Downie CG, Shearer JJ, Kuku KO … +5 more , Bielinski SJ, Kizer JR, Psaty BM, Joo J, Roger VL
Circ Genom Precis Med · 2025 Aug · PMID 40665907 · Full text
BACKGROUND: Heart failure (HF) is a heterogeneous syndrome with high mortality. The need for a new taxonomy of HF is recognized; up to now, such phenomapping efforts have primarily used clinical data. Proteomics offers p...
BACKGROUND: Heart failure (HF) is a heterogeneous syndrome with high mortality. The need for a new taxonomy of HF is recognized; up to now, such phenomapping efforts have primarily used clinical data. Proteomics offers potential for more precise phenotypic identification and mechanistic insights. However, few phenomapping studies have used this approach, and all have focused on targeted cardiovascular proteomics panels and a restricted HF ejection fraction group. METHODS: We measured over 7000 plasma proteins in a population-based cohort of 1351 patients with HF, used k-means clustering to identify distinct phenogroups, and compared their clinical characteristics and all-cause mortality. RESULTS: Three proteomics-defined phenogroups were identified, with substantial differences in survival (phenogroup 1 5-year survival probability, 65% [95% CI, 61%-68%]; phenogroup 2, 45% [40%-51%]; phenogroup 3, 26% [22%-30%]), independent of clinical characteristics. Phenogroups also exhibited differences in several measures suggesting poorer health, including NT-proBNP (N-terminal pro-B-type natriuretic peptide), kidney function, and Meta-Analysis Global Group in Chronic Heart Failure scores, but did not differ by ejection fraction or New York Heart Association class. CONCLUSIONS: Our study demonstrates that molecular phenomapping can stratify patients with HF into distinct subgroups that go beyond predefined clinical classifications.
Midterm Outcomes in a Pooled Cohort of Harmony Transcatheter Pulmonary Valve Recipients.
Morray BH, Gillespie MJ, Cheatham JP … +13 more , Salavitabar A, Peng L, Jones TK, Levi DS, Gray RG, Asnes J, Cabalka AK, Fujimoto K, Qureshi AM, Bergersen L, Benson LN, Haugan D, McElhinney DB
Circ Cardiovasc Interv · 2025 Sep · PMID 40665900 · Full text
BACKGROUND: The Harmony transcatheter pulmonary valve (TPV) is designed to treat severe pulmonary regurgitation in the native or surgically repaired right ventricular (RV) outflow tract. Early outcomes after TPV replacem...
BACKGROUND: The Harmony transcatheter pulmonary valve (TPV) is designed to treat severe pulmonary regurgitation in the native or surgically repaired right ventricular (RV) outflow tract. Early outcomes after TPV replacement with the Harmony valve have been positive, but longer-term data are limited. METHODS: The study included patients who received a commercially available TPV22 or TPV25 device as part of the nonrandomized, prospective Native Outflow Tract Early Feasibility Study, Harmony Pivotal Trial, and Continued Access Study. Patients completed at least 3 years of follow-up, and outcomes to 5 years were reported when available. RESULTS: Eighty-nine patients were catheterized, and 86 were successfully implanted with a Harmony TPV. Median duration of follow-up was 5 (range 0-6) years in the TPV22 group and 3 (1-4) years in the TPV25 group. At 3 years, all patients with a TPV22 and 96% of those with a TPV25 had ≤mild pulmonary regurgitation. By magnetic resonance imaging, significant improvements from preimplant to 2 years were observed in RV end-diastolic volume index, RV to left ventricular end-diastolic volume ratio, and effective RV stroke volume (all <0.001). SF-36 quality-of-life scores improved after Harmony implantation and were sustained over 3 years. Early cases of ventricular tachycardia resolved, and there were no new arrhythmias. Adverse events up to 5 years included 3 deaths unrelated to the device or procedure, 2 cases of endocarditis that were treated (1 medically, 1 transcatheter debulking of a vegetation) and resolved, 6 patients with RV outflow tract obstruction or thrombosis resulting in valve-in valve procedures, and 1 major stent fracture resulting in surgical explant. CONCLUSIONS: At 3 to 5 years, Harmony TPV replacement resulted in sustained valve competence, beneficial cardiac remodeling, and improved quality of life. Continued monitoring is needed to assess long-term outcomes and valve performance. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT01762124; NCT02979587.
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