Stroke; A Journal Of Cerebral Circulation[JOURNAL]
Sun
200 papers
Effect of Empagliflozin as an Add-On Therapy on Decongestion and Renal Function in Patients With Diabetes Hospitalized for Acute Decompensated Heart Failure: A Prospective Randomized Controlled Study.
Tamaki S, Yamada T, Watanabe T … +20 more , Morita T, Furukawa Y, Kawasaki M, Kikuchi A, Kawai T, Seo M, Abe M, Nakamura J, Yamamoto K, Kayama K, Kawahira M, Tanabe K, Fujikawa K, Hata M, Fujita Y, Umayahara Y, Taniuchi S, Sanada S, Shintani A, Fukunami M
Circ Heart Fail · 2021 Mar · PMID 33663235 · Publisher ↗
BACKGROUND: Empagliflozin reduces the risk of hospitalization for heart failure in patients with type 2 diabetes and cardiovascular disease. We sought to elucidate the effect of empagliflozin as an add-on therapy on deco...
BACKGROUND: Empagliflozin reduces the risk of hospitalization for heart failure in patients with type 2 diabetes and cardiovascular disease. We sought to elucidate the effect of empagliflozin as an add-on therapy on decongestion and renal function in patients with type 2 diabetes admitted for acute decompensated heart failure. METHODS: The study was terminated early due to COVID-19 pandemic. We enrolled 59 consecutive patients with type 2 diabetes admitted for acute decompensated heart failure. Patients were randomly assigned to receive either empagliflozin add-on (n=30) or conventional glucose-lowering therapy (n=29). We performed laboratory tests at baseline and 1, 2, 3, and 7 days after randomization. Percent change in plasma volume between admission and subsequent time points was calculated using the Strauss formula. RESULTS: There were no significant baseline differences in left ventricular ejection fraction and serum NT-proBNP (N-terminal pro-B-type natriuretic peptide), hematocrit, or serum creatinine levels between the 2 groups. Seven days after randomization, NT-proBNP level was significantly lower in the empagliflozin group than in the conventional group (=0.040), and hemoconcentration (≥3% absolute increase in hematocrit) was more frequently observed in the empagliflozin group than in the conventional group (=0.020). The decrease in percent change in plasma volume between baseline and subsequent time points was significantly larger in the empagliflozin group than in the conventional group 7 days after randomization (=0.017). The incidence of worsening renal function (an increase in serum creatinine ≥0.3 mg/dL) did not significantly differ between the 2 groups. CONCLUSIONS: In this exploratory analysis, empagliflozin achieved effective decongestion without an increased risk of worsening renal function as an add-on therapy in patients with type 2 diabetes with acute decompensated heart failure. Registration: URL: https://www.umin.ac.jp/ctr/index.htm; Unique identifier: UMIN000026315.
Impact of Global Budget Payments on Cardiovascular Care in Maryland: An Interrupted Time Series Analysis.
Viganego F, Um EK, Ruffin J … +3 more , Fradley MG, Prida X, Friebel R
Circ Cardiovasc Qual Outcomes · 2021 Mar · PMID 33622052 · Publisher ↗
Background Global budget payments (GBP) are considered effective in containing health care expenditures; however, information on their impact on quality of cardiovascular care is limited. We aimed to evaluate the effects...
Background Global budget payments (GBP) are considered effective in containing health care expenditures; however, information on their impact on quality of cardiovascular care is limited. We aimed to evaluate the effects of GBP on utilization, outcomes, and costs for 3 major cardiovascular conditions. Methods We analyzed claims data of hospital admissions in Maryland from fiscal year 2013 to 2018. Using segmented regression, we evaluated temporal trends in hospitalizations, length of stay, percutaneous coronary intervention and coronary artery bypass grafting volumes, case mix-adjusted 30-day readmission rates, risk-standardized mortality rates, and hospitalization charges in patients with principal diagnosis of heart failure, acute ischemic stroke, and acute myocardial infarction (AMI) in relation to GBP implementation. Trends in global cardiovascular procedure charges/volumes were also studied. Results Hospitalization rates for congestive heart failure and AMI remained unaffected by GBP, while the gradient of ischemic stroke admissions decreased ( <0.0001). Length of stay slightly increased for patients with congestive heart failure (=0.03). Inpatient coronary artery bypass grafting surgeries decreased ( <0.0001). We observed a significant decrease in casemix-adjusted 30-day readmission rate in the AMI cohort beyond the prepolicy trend (=0.0069). There were no significant changes in mortality for any of the 3 conditions. Hospitalization charges increased for ischemic stroke ( <0.0001), remained constant for congestive heart failure (=0.1), and decreased for AMI (=0.0005). We observed a significant increase in electrocardiography rate charges ( <0.0001), coincidentally with a reduction in volumes (=0.0003). Conclusions Introducing GBP in Maryland had no perceivable adverse effects on inpatient outcomes and quality indicators for 3 major cardiovascular conditions. Savings were observed in the AMI cohort, possibly due to reduced unnecessary readmissions, efficiency improvements, or shifts to outpatient care. Reduced cardiovascular procedure volumes were counterbalanced by a proportional rise in charges. State-level adoption of GBP with pay-for-performance incentives may be effective for cost containment without adversely impacting quality of cardiovascular care.
Cerebral Embolic Protection and Outcomes of Transcatheter Aortic Valve Replacement: Results From the Transcatheter Valve Therapy Registry.
Butala NM, Makkar R, Secemsky EA … +9 more , Gallup D, Marquis-Gravel G, Kosinski AS, Vemulapalli S, Valle JA, Bradley SM, Chakravarty T, Yeh RW, Cohen DJ
Circulation · 2021 Jun · PMID 33619968 · Full text
BACKGROUND: Stroke remains a devastating complication of transcatheter aortic valve replacement (TAVR), which has persisted despite refinements in technique and increased operator experience. While cerebral embolic prote...
BACKGROUND: Stroke remains a devastating complication of transcatheter aortic valve replacement (TAVR), which has persisted despite refinements in technique and increased operator experience. While cerebral embolic protection devices (EPDs) have been developed to mitigate this risk, data regarding their impact on stroke and other outcomes after TAVR are limited. METHODS: We performed an observational study using data from the Society for Thoracic Surgeons/American College of Cardiology Transcatheter Valve Therapy Registry. Patients were included if they underwent elective or urgent transfemoral TAVR between January 2018 and December 2019. The primary outcome was in-hospital stroke. To adjust for confounding, the association between EPD use and clinical outcomes was evaluated using instrumental variable analysis, a technique designed to support causal inference from observational data, with site-level preference for EPD use within the same quarter of the procedure as the instrument. We also performed a propensity score-based secondary analysis using overlap weights. RESULTS: Our analytic sample included 123 186 patients from 599 sites. The use of EPD during TAVR increased over time, reaching 28% of sites and 13% of TAVR procedures by December 2019. There was wide variation in EPD use across hospitals, with 8% of sites performing >50% of TAVR procedures with an EPD and 72% performing no procedures with an EPD in the last quarter of 2019. In our primary analysis using the instrumental variable model, there was no association between EPD use and in-hospital stroke (adjusted relative risk, 0.90 [95% CI, 0.68-1.13]; absolute risk difference, -0.15% [95% CI, -0.49 to 0.20]). However, in our secondary analysis using the propensity score-based model, EPD use was associated with 18% lower odds of in-hospital stroke (adjusted odds ratio, 0.82 [95% CI, 0.69-0.97]; absolute risk difference, -0.28% [95% CI, -0.52 to -0.03]). Results were generally consistent across the secondary end points, as well as subgroup analyses. CONCLUSIONS: In this nationally representative observational study, we did not find an association between EPD use for TAVR and in-hospital stroke in our primary instrumental variable analysis, and found only a modestly lower risk of in-hospital stroke in our secondary propensity-weighted analysis. These findings provide a strong basis for large-scale randomized, controlled trials to test whether EPDs provide meaningful clinical benefit for patients undergoing TAVR.
Maternal Stroke: A Call for Action.
Elgendy IY, Bukhari S, Barakat AF … +4 more , Pepine CJ, Lindley KJ, Miller EC, American College of Cardiology Cardiovascular Disease in Women Committee
Circulation · 2021 Feb · PMID 33587666 · Full text
Maternal mortality rates have been steadily increasing in the United States, and cardiovascular mortality is the leading cause of death among pregnant and postpartum women. Maternal stroke accounts for a significant burd...
Maternal mortality rates have been steadily increasing in the United States, and cardiovascular mortality is the leading cause of death among pregnant and postpartum women. Maternal stroke accounts for a significant burden of cardiovascular mortality. Data suggest that rates of maternal stroke have been increasing in recent years. Advancing maternal age at the time of birth and the increasing prevalence of traditional cardiovascular risk factors, and other risk factors, as well, such as hypertensive disorders of pregnancy, migraine, and infections, may contribute to increased rates of maternal stroke. In this article, we provide an overview of the epidemiology of maternal stroke, explore mechanisms that may explain increasing rates of stroke among pregnant women, and identify key knowledge gaps for future investigation in this area.
Heart Disease and Stroke Statistics-2021 Update: A Report From the American Heart Association.
Virani SS, Alonso A, Aparicio HJ … +37 more , Benjamin EJ, Bittencourt MS, Callaway CW, Carson AP, Chamberlain AM, Cheng S, Delling FN, Elkind MSV, Evenson KR, Ferguson JF, Gupta DK, Khan SS, Kissela BM, Knutson KL, Lee CD, Lewis TT, Liu J, Loop MS, Lutsey PL, Ma J, Mackey J, Martin SS, Matchar DB, Mussolino ME, Navaneethan SD, Perak AM, Roth GA, Samad Z, Satou GM, Schroeder EB, Shah SH, Shay CM, Stokes A, VanWagner LB, Wang NY, Tsao CW, American Heart Association Council on Epidemiology and Prevention Statistics Committee and Stroke Statistics Subcommittee
Circulation · 2021 Feb · PMID 33501848 · Full text
BACKGROUND: The American Heart Association, in conjunction with the National Institutes of Health, annually reports the most up-to-date statistics related to heart disease, stroke, and cardiovascular risk factors, includ...
BACKGROUND: The American Heart Association, in conjunction with the National Institutes of Health, annually reports the most up-to-date statistics related to heart disease, stroke, and cardiovascular risk factors, including core health behaviors (smoking, physical activity, diet, and weight) and health factors (cholesterol, blood pressure, and glucose control) that contribute to cardiovascular health. The Statistical Update presents the latest data on a range of major clinical heart and circulatory disease conditions (including stroke, congenital heart disease, rhythm disorders, subclinical atherosclerosis, coronary heart disease, heart failure, valvular disease, venous disease, and peripheral artery disease) and the associated outcomes (including quality of care, procedures, and economic costs). METHODS: The American Heart Association, through its Statistics Committee, continuously monitors and evaluates sources of data on heart disease and stroke in the United States to provide the most current information available in the annual Statistical Update. The 2021 Statistical Update is the product of a full year's worth of effort by dedicated volunteer clinicians and scientists, committed government professionals, and American Heart Association staff members. This year's edition includes data on the monitoring and benefits of cardiovascular health in the population, an enhanced focus on social determinants of health, adverse pregnancy outcomes, vascular contributions to brain health, the global burden of cardiovascular disease, and further evidence-based approaches to changing behaviors related to cardiovascular disease. RESULTS: Each of the 27 chapters in the Statistical Update focuses on a different topic related to heart disease and stroke statistics. CONCLUSIONS: The Statistical Update represents a critical resource for the lay public, policy makers, media professionals, clinicians, health care administrators, researchers, health advocates, and others seeking the best available data on these factors and conditions.
Research Priorities in Atrial Fibrillation Screening: A Report From a National Heart, Lung, and Blood Institute Virtual Workshop.
Benjamin EJ, Go AS, Desvigne-Nickens P … +23 more , Anderson CD, Casadei B, Chen LY, Crijns HJGM, Freedman B, Hills MT, Healey JS, Kamel H, Kim DY, Link MS, Lopes RD, Lubitz SA, McManus DD, Noseworthy PA, Perez MV, Piccini JP, Schnabel RB, Singer DE, Tieleman RG, Turakhia MP, Van Gelder IC, Cooper LS, Al-Khatib SM
Circulation · 2021 Jan · PMID 33493033 · Full text
Clinically recognized atrial fibrillation (AF) is associated with higher risk of complications, including ischemic stroke, cognitive decline, heart failure, myocardial infarction, and death. It is increasingly recognized...
Clinically recognized atrial fibrillation (AF) is associated with higher risk of complications, including ischemic stroke, cognitive decline, heart failure, myocardial infarction, and death. It is increasingly recognized that AF frequently is undetected until complications such as stroke or heart failure occur. Hence, the public and clinicians have an intense interest in detecting AF earlier. However, the most appropriate strategies to detect undiagnosed AF (sometimes referred to as subclinical AF) and the prognostic and therapeutic implications of AF detected by screening are uncertain. Our report summarizes the National Heart, Lung, and Blood Institute's virtual workshop focused on identifying key research priorities related to AF screening. Global experts reviewed major knowledge gaps and identified critical research priorities in the following areas: (1) role of opportunistic screening; (2) AF as a risk factor, risk marker, or both; (3) relationship between AF burden detected with long-term monitoring and outcomes/treatments; (4) designs of potential randomized trials of systematic AF screening with clinically relevant outcomes; and (5) role of AF screening after ischemic stroke. Our report aims to inform and catalyze AF screening research that will advance innovative, resource-efficient, and clinically relevant studies in diverse populations to improve the diagnosis, management, and prognosis of patients with undiagnosed AF.
Stroke Prevention in Atrial Fibrillation: Looking Forward.
Katsanos AH, Kamel H, Healey JS … +1 more , Hart RG
Circulation · 2020 Dec · PMID 33315494 · Publisher ↗
Ischemic strokes related to atrial fibrillation are highly prevalent, presenting with severe neurologic syndromes and associated with high risk of recurrence. Although advances have been made in both primary and secondar...
Ischemic strokes related to atrial fibrillation are highly prevalent, presenting with severe neurologic syndromes and associated with high risk of recurrence. Although advances have been made in both primary and secondary stroke prevention for patients with atrial fibrillation, the long-term risks for stroke recurrence and bleeding complications from antithrombotic treatment remain substantial. We summarize the major advances in stroke prevention for patients with atrial fibrillation during the past 30 years and focus on novel diagnostic and treatment approaches currently under investigation in ongoing clinical trials. Non-vitamin K antagonist oral anticoagulants have been proven to be safer and equally effective compared with warfarin in stroke prevention for patients with nonvalvular atrial fibrillation. Non-vitamin K antagonist oral anticoagulants are being investigated for the treatment of patients with atrial fibrillation and rheumatic heart disease, for the treatment of patients with recent embolic stroke of undetermined source and indirect evidence of cardiac embolism, and in the prevention of vascular-mediated cognitive decline in patients with atrial fibrillation. Multiple clinical trials are assessing the optimal timing of non-vitamin K antagonist oral anticoagulant initiation after a recent ischemic stroke and the benefit:harm ratio of non-vitamin K antagonist oral anticoagulant treatment in patients with atrial fibrillation and history of previous intracranial bleeding. Ongoing trials are addressing the usefulness of left atrial appendage occlusion in both primary and secondary stroke prevention for patients with atrial fibrillation, including those with high risk of bleeding. The additive value of prolonged cardiac monitoring for subclinical atrial fibrillation detection through smartphone applications or implantable cardiac devices, together with the optimal medical management of individuals with covert paroxysmal atrial fibrillation, is a topic of intensive research interest. Colchicine treatment and factor XIa inhibition constitute 2 novel pharmacologic approaches that might provide future treatment options in the secondary prevention of cardioembolic stroke attributable to atrial fibrillation.
Target: Stroke Was Associated With Faster Intravenous Thrombolysis and Improved One-Year Outcomes for Acute Ischemic Stroke in Medicare Beneficiaries.
Man S, Xian Y, Holmes DN … +6 more , Matsouaka RA, Saver JL, Smith EE, Bhatt DL, Schwamm LH, Fonarow GC
Circ Cardiovasc Qual Outcomes · 2020 Dec · PMID 33302714 · Publisher ↗
BACKGROUND: The benefit of intravenous thrombolytic therapy for acute ischemic stroke is time dependent. To assist hospitals in providing faster thrombolytic treatment, the American Heart Association launched target: str...
BACKGROUND: The benefit of intravenous thrombolytic therapy for acute ischemic stroke is time dependent. To assist hospitals in providing faster thrombolytic treatment, the American Heart Association launched target: stroke quality initiative in January 2010 which disseminated feasible strategies to shorten door-to-needle times for thrombolytic therapy. This study aimed to examine whether target: stroke was associated with improved door-to-needle times and 1-year outcomes. METHODS: We analyzed Medicare beneficiaries aged ≥65 years receiving intravenous thrombolytic treatment for acute ischemic stroke at 1490 Get With The Guidelines-Stroke hospitals during January 2006 and December 2009 (preintervention, n=10 804) and January 2010 and December 2014 (postintervention, n=31 249). The median age was 80 years and 42.7% were male. RESULTS: The median door-to-needle times decreased from 80 minutes for the preintervention to 68 minutes for the postintervention (<0.001). The proportion of patients receiving intravenous thrombolysis with door-to-needle times 45 minutes and 60 minutes increased from 9.6% and 24.8% for preintervention to 17.1% and 40.6% for postintervention, respectively (<0.001). The annual rate of increase in the door-to-needle times of 60 minutes or less accelerated from 0.20% (95% CI, -0.43% to 0.83%) per each 4 quarters for preintervention to 5.68% (95% CI, 5.23%-6.13%) for postintervention (<0.001) which was further confirmed in piecewise multivariable generalized estimating analysis (adjusted odds ratio, 1.27 [95% CI, 1.19-1.35]). Cox proportional hazards analysis, after adjusting for patient and hospital characteristics and within-hospital clustering, showed that target: stroke was associated with lower all-cause readmission (40.4% versus 44.1%; hazard ratio, 0.91 [95% CI, 0.88-0.95]), cardiovascular readmission (19.7% versus 22.9%; hazard ratio, 0.85 [95% CI, 0.80-0.89]), and composite of all-cause mortality or readmission (56.0% versus 58.4%; hazard ratio, 0.96 [95% CI, 0.93-1.00]). The risk decline in all-cause mortality dissipated after risk adjustment (adjusted hazard ratio, 0.98 [95% CI, 0.94-1.02]). CONCLUSIONS: Target: stroke quality initiative was associated with faster thrombolytic treatment times for acute ischemic stroke and modestly lower 1-year all-cause and cardiovascular readmissions.
Surviving Severe Stroke-Our Next Big Challenge: Clinical Commentary on "The 'Less Than' Life?".
Zahuranec DB, Creutzfeldt CJ
Circ Cardiovasc Qual Outcomes · 2020 Dec · PMID 33280433 · Publisher ↗
Abstract loading — click title to view on PubMed.
The "Less Than" Life?
Van Kirk S
Circ Cardiovasc Qual Outcomes · 2020 Dec · PMID 33280432 · Publisher ↗
Abstract loading — click title to view on PubMed.
Association of White Matter Hyperintensities and Cardiovascular Disease: The Importance of Microcirculatory Disease.
Moroni F, Ammirati E, Hainsworth AH … +1 more , Camici PG
Circ Cardiovasc Imaging · 2020 Aug · PMID 33232175 · Publisher ↗
Cardiac and cerebrovascular diseases are currently the leading causes of mortality and disability worldwide. Both the heart and brain display similar vascular anatomy, with large conduit arteries running on the surface o...
Cardiac and cerebrovascular diseases are currently the leading causes of mortality and disability worldwide. Both the heart and brain display similar vascular anatomy, with large conduit arteries running on the surface of the organ providing tissue perfusion through an intricate network of penetrating small vessels. Both organs rely on fine tuning of local blood flow to match metabolic demand. Blood flow regulation requires adequate functioning of the microcirculation in both organs, with loss of microvascular function, termed small vessel disease (SVD) underlying different potential clinical manifestations. SVD in the heart, known as coronary microvascular dysfunction, can cause chronic or acute myocardial ischemia and may lead to development of heart failure. In the brain, cerebral SVD can cause an acute stroke syndrome known as lacunar stroke or more subtle pathological alterations of the brain parenchyma, which may eventually lead to neurological deficits or cognitive decline in the long term. Coronary microcirculation cannot be visualized in vivo in humans, and functional information can be deduced by measuring the coronary flow reserve. The diagnosis of cerebral SVD is largely based on brain magnetic resonance imaging, with white matter hyperintensities, microbleeds, and brain atrophy reflecting key structural changes. There is evidence that such structural changes reflect underlying cerebral SVD. Here, we review interactions between SVD and cardiovascular risk factors, and we discuss the evidence linking cerebral SVD with large vessel atheroma, atrial fibrillation, heart failure, and heart valve disease.
Efficacy of Dapagliflozin on Renal Function and Outcomes in Patients With Heart Failure With Reduced Ejection Fraction: Results of DAPA-HF.
Jhund PS, Solomon SD, Docherty KF … +24 more , Heerspink HJL, Anand IS, Böhm M, Chopra V, de Boer RA, Desai AS, Ge J, Kitakaze M, Merkley B, O'Meara E, Shou M, Tereshchenko S, Verma S, Vinh PN, Inzucchi SE, Køber L, Kosiborod MN, Martinez FA, Ponikowski P, Sabatine MS, Bengtsson O, Langkilde AM, Sjöstrand M, McMurray JJV
Circulation · 2021 Jan · PMID 33040613 · Full text
BACKGROUND: Many patients with heart failure and reduced ejection fraction (HFrEF) have chronic kidney disease that complicates pharmacological management and is associated with worse outcomes. We assessed the safety and...
BACKGROUND: Many patients with heart failure and reduced ejection fraction (HFrEF) have chronic kidney disease that complicates pharmacological management and is associated with worse outcomes. We assessed the safety and efficacy of dapagliflozin in patients with HFrEF, according to baseline kidney function, in the DAPA-HF trial (Dapagliflozin and Prevention of Adverse-outcomes in Heart Failure). We also examined the effect of dapagliflozin on kidney function after randomization. METHODS: Patients who have HFrEF with or without type 2 diabetes and an estimated glomerular filtration rate (eGFR) ≥30 mL·min·1.73 m were enrolled in DAPA-HF. We calculated the incidence of the primary outcome (cardiovascular death or worsening heart failure) according to eGFR category at baseline (<60 and ≥60 mL·min·1.73 m) and used eGFR at baseline as a continuous measure, as well. Secondary cardiovascular outcomes and a prespecified composite renal outcome (≥50% sustained decline eGFR, end-stage renal disease, or renal death) were also examined, along with a decline in eGFR over time. RESULTS: Of 4742 patients with a baseline eGFR, 1926 (41%) had eGFR <60 mL·min·1.73 m. The effect of dapagliflozin on the primary and secondary outcomes did not differ by eGFR category or examining eGFR as a continuous measurement. The hazard ratio (95% CI) for the primary end point in patients with chronic kidney disease was 0.71 (0.59-0.86) versus 0.77 (0.64-0.93) in those with an eGFR ≥60 mL·min·1.73 m (interaction =0.54). The composite renal outcome was not reduced by dapagliflozin (hazard ratio=0.71 [95% CI, 0.44-1.16]; =0.17) but the rate of decline in eGFR between day 14 and 720 was less with dapagliflozin, -1.09 (-1.40 to -0.77) versus placebo -2.85 (-3.17 to -2.53) mL·min·1.73 m per year (<0.001). This was observed in those with and without type 2 diabetes ( for interaction=0.92). CONCLUSIONS: Baseline kidney function did not modify the benefits of dapagliflozin on morbidity and mortality in HFrEF, and dapagliflozin slowed the rate of decline in eGFR, including in patients without diabetes. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03036124.
Racial and Ethnic Differences in Biomarkers, Health Status, and Cardiac Remodeling in Patients With Heart Failure With Reduced Ejection Fraction Treated With Sacubitril/Valsartan.
Ibrahim NE, Piña IL, Camacho A … +9 more , Bapat D, Felker GM, Maisel AS, Butler J, Prescott MF, Abbas CA, Solomon SD, Januzzi JL, Prospective Study of Biomarkers, Symptom Improvement and Ventricular Remodeling During Entresto Therapy for Heart Failure (PROVE-HF) Study Investigators
Circ Heart Fail · 2020 Nov · PMID 33016100 · Full text
BACKGROUND: Among patients with heart failure and reduced ejection fraction (left ventricular (LV) ejection fraction ≤40%), sacubitril/valsartan (S/V) treatment is associated with improved health status and reverse cardi...
BACKGROUND: Among patients with heart failure and reduced ejection fraction (left ventricular (LV) ejection fraction ≤40%), sacubitril/valsartan (S/V) treatment is associated with improved health status and reverse cardiac remodeling. Data regarding racial and ethnic differences in response to S/V are lacking. METHODS: This was an analysis from the PROVE-HF study (Prospective Study of Biomarkers, Symptom Improvement and Ventricular Remodeling During Entresto Therapy for Heart Failure). Longitudinal changes in NT-proBNP (N-terminal pro-B-type natriuretic peptide), cardiac reverse remodeling, and health status scores were compared between groups using multivariate latent growth curve modeling. RESULTS: Among the 782 patients included in this study, 22.7% were non-Hispanic Black (from here referred to as Black), 14.9% were Hispanic, and 62.4% were non-Hispanic White (from here referred to as White). At baseline, compared with White patients, Black and Hispanic patients had lower NT-proBNP (=0.34) and differences between groups in baseline values for LV end-diastolic volume index and LV end-systolic volume index were negligible (<0.10). Following S/V initiation, NT-proBNP decreased in all 3 groups (<0.0001) associated with improvements in LV ejection fraction, LV end-diastolic volume index, and LV end-systolic volume index. Although total improvement in LV measures was similar between groups, Black patients averaged larger gains in the first half of the trial while White patients averaged larger gains in the second half. Improvements in Kansas City Cardiomyopathy Questionnaire-23 Total Symptom scores were seen in all 3 groups. Treatment with S/V was well-tolerated. CONCLUSIONS: Among Black, Hispanic, and White patients with heart failure and reduced ejection fraction, treatment with S/V was associated with similar reduction in NT-proBNP, improvement in health status, and reverse remodeling. More data regarding racial and ethnic responses to heart failure and reduced ejection fraction treatment are needed. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02887183.
Atrial Fibrillation and Dementia.
Bunch TJ
Circulation · 2020 Aug · PMID 32804567 · Publisher ↗
Atrial fibrillation is associated with multiple adverse comorbidities, including the development of dementia in patients with and without a history of stroke. Mechanistic models have been proposed to explain the associat...
Atrial fibrillation is associated with multiple adverse comorbidities, including the development of dementia in patients with and without a history of stroke. Mechanistic models have been proposed to explain the association of AF and dementia. Alterations of brain perfusion from embolic events, bleeding, and rhythm-related hypoperfusion underlie many of these models. Multiple mediators such as oxidative injury, inflammatory and autoimmune mechanisms, and genetic predisposition also interplay in the disease association. There are potential therapeutic opportunities to reduce dementia risk, including early and effective use of anticoagulation and strategies to improve brain perfusion through rhythm and rate control approaches. Prospective trials are needed to evaluate these therapeutic opportunities that carefully measure cognitive function and dementia incidence.
Cardiac Emerinopathy: A Nonsyndromic Nuclear Envelopathy With Increased Risk of Thromboembolic Stroke Due to Progressive Atrial Standstill and Left Ventricular Noncompaction.
Ishikawa T, Mishima H, Barc J … +21 more , Takahashi MP, Hirono K, Terada S, Kowase S, Sato T, Mukai Y, Yui Y, Ohkubo K, Kimoto H, Watanabe H, Hata Y, Aiba T, Ohno S, Chishaki A, Shimizu W, Horie M, Ichida F, Nogami A, Yoshiura KI, Schott JJ, Makita N
Circ Arrhythm Electrophysiol · 2020 Oct · PMID 32755394 · Publisher ↗
BACKGROUND: Mutations in the nuclear envelope genes encoding and are responsible for Emery-Dreifuss muscular dystrophy. However, mutations often manifest dilated cardiomyopathy with conduction disturbance without obvi...
BACKGROUND: Mutations in the nuclear envelope genes encoding and are responsible for Emery-Dreifuss muscular dystrophy. However, mutations often manifest dilated cardiomyopathy with conduction disturbance without obvious skeletal myopathic complications. On the contrary, the phenotypic spectrums of mutations are less clear. Our aims were to determine the prevalence of nonsyndromic forms of emerinopathy, which may underlie genetically undefined isolated cardiac conduction disturbance, and the etiology of thromboembolic complications associated with mutations. METHODS: Targeted exon sequencing was performed in 87 probands with familial sick sinus syndrome (n=36) and a progressive cardiac conduction defect (n=51). RESULTS: We identified 3 X-linked recessive mutations (start-loss, splicing, missense) in families with cardiac conduction disease. All 3 probands shared a common clinical phenotype of progressive atrial arrhythmias that ultimately resulted in atrial standstill associated with left ventricular noncompaction (LVNC), but they lacked early contractures and progressive muscle wasting and weakness characteristic of Emery-Dreifuss muscular dystrophy. Because the association of LVNC with has never been reported, we further genetically screened 102 LVNC patients and found a frameshift mutation in a boy with progressive atrial standstill and LVNC without complications of muscular dystrophy. All 6 male mutation carriers of 4 families underwent pacemaker or defibrillator implantation, whereas 2 female carriers were asymptomatic. Notably, a strong family history of stroke observed in these families was probably due to the increased risk of thromboembolism attributable to both atrial standstill and LVNC. CONCLUSIONS: Cardiac emerinopathy is a novel nonsyndromic X-linked progressive atrial standstill associated with LVNC and increased risk of thromboembolism.
Radionuclide Imaging of the Molecular Mechanisms Linking Heart and Brain in Ischemic Syndromes.
Bengel FM, Hermanns N, Thackeray JT
Circ Cardiovasc Imaging · 2020 Aug · PMID 35939791 · Publisher ↗
For the heart and the brain, clinical observations suggest that an acute ischemic event experienced by one organ is associated with an increased risk for future acute events and chronic dysfunction of the reciprocal orga...
For the heart and the brain, clinical observations suggest that an acute ischemic event experienced by one organ is associated with an increased risk for future acute events and chronic dysfunction of the reciprocal organ. Beyond atherosclerosis as a common systemic disease, various molecular mechanisms are thought to be involved in this interaction. Molecular-targeted nuclear imaging may identify the contribution of factors, such as the neurohumoral, circulatory, or especially the immune system, by combining specific radiotracers with whole-body acquisition and global as well as regional multiorgan analysis. This may be integrated with complementary functional imaging markers and systemic biomarkers for comprehensive network interrogation. Such systems-based strategies go beyond the traditional organ-centered approach and provide novel mechanistic insights, information about temporal dynamics, and a foundation for future interventions aiming at optimal preservation of function of both organs.
Carotid Atherosclerosis Evolution When Targeting a Low-Density Lipoprotein Cholesterol Concentration <70 mg/dL After an Ischemic Stroke of Atherosclerotic Origin.
Amarenco P, Hobeanu C, Labreuche J … +8 more , Charles H, Giroud M, Meseguer E, Lavallée PC, Gabriel Steg P, Vicaut É, Bruckert E, Touboul PJ
Circulation · 2020 Aug · PMID 32594766 · Publisher ↗
BACKGROUND: The TST trial (Treat Stroke to Target) showed the benefit of targeting a low-density lipoprotein cholesterol (LDL-C) concentration of <70 mg/dL in terms of reducing the risk of major cardiovascular events in...
BACKGROUND: The TST trial (Treat Stroke to Target) showed the benefit of targeting a low-density lipoprotein cholesterol (LDL-C) concentration of <70 mg/dL in terms of reducing the risk of major cardiovascular events in 2860 patients with ischemic stroke with atherosclerotic stenosis of cerebral vasculature. The impact on carotid atherosclerosis evolution is not known. METHODS: TST-PLUS (Treat Stroke to Target-Plaque Ultrasound Study) included 201 patients assigned to an LDL-C concentration of <70 mg/dL and 212 patients assigned to a target of 100±10 mg/dL. To achieve these goals, investigators used the statin and dosage of their choice and added ezetimibe as needed. Ultrasonographers were certified and carotid ultrasound examinations were performed using M'Ath software at baseline and at 2, 3, and 5 years. All images were uploaded to the Intelligence in Medical Technologies database directly from the carotid ultrasound device. The central core laboratory performed all offline measurements of the intima-media thickness of both common carotid arteries blinded from the randomization arm. The main outcomes were newly diagnosed atherosclerotic plaque on carotid bifurcation or internal carotid artery using the Mannheim consensus definition and between-group comparison of common carotid arteries intima-media thickness change. RESULTS: After a median follow-up of 3.1 years, the achieved LDL-C concentrations were 64 mg/dL (1.64 mmol/L) in the lower-target group and 106 mg/dL (2.72 mmol/L) in the higher-target group. Compared with the higher-target group, patients in the lower-target group had a similar incidence of newly diagnosed carotid plaque: 46/201 (5-year rate, 26.1%) versus 45/212 (5-year rate, 29.7%). The change in common carotid arteries intima-media thickness was -2.69 µm (95% CI, -6.55 to 1.18) in the higher-target group and -10.53 µm (95% CI, -14.21 to -6.85) in the lower-target group, resulting in an absolute between-group difference of -7.84 µm (95% CI, -13.18 to -2.51; =0.004). CONCLUSIONS: In patients with ischemic stroke and atherosclerosis, an LDL-C target of <70 mg/dL (1.8 mmol/L) did not reduce the incidence of new carotid plaques but produced significantly greater regression of carotid atherosclerosis than an LDL-C target of 90 to 110 mg/dL. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT01252875.
Extracellular Vesicle-Mediated Delivery of Circular RNA SCMH1 Promotes Functional Recovery in Rodent and Nonhuman Primate Ischemic Stroke Models.
Yang L, Han B, Zhang Z … +25 more , Wang S, Bai Y, Zhang Y, Tang Y, Du L, Xu L, Wu F, Zuo L, Chen X, Lin Y, Liu K, Ye Q, Chen B, Li B, Tang T, Wang Y, Shen L, Wang G, Ju M, Yuan M, Jiang W, Zhang JH, Hu G, Wang J, Yao H
Circulation · 2020 Aug · PMID 32441115 · Publisher ↗
BACKGROUND: Stroke is a leading cause of adult disability that can severely compromise the quality of life of patients, yet no effective medication currently exists to accelerate rehabilitation. A variety of circular RNA...
BACKGROUND: Stroke is a leading cause of adult disability that can severely compromise the quality of life of patients, yet no effective medication currently exists to accelerate rehabilitation. A variety of circular RNA (circRNA) molecules are known to function in ischemic brain injury. Lentivirus-based expression systems have been widely used in basic studies of circRNAs, but safety issues with such delivery systems have limited exploration of the potential therapeutic roles for circRNAs. METHODS: Circular RNA SCMH1 (circSCMH1) was screened from the plasma of patients with acute ischemic stroke by using circRNA microarrays. Engineered rabies virus glycoprotein-circSCMH1-extracellular vesicles were generated to selectively deliver circSCMH1 to the brain. Nissl staining was used to examine infarct size. Behavioral tasks were performed to evaluate motor functions in both rodent and nonhuman primate ischemic stroke models. Golgi staining and immunostaining were used to examine neuroplasticity and glial activation. Proteomic assays and RNA-sequencing data combined with transcriptional profiling were used to identify downstream targets of circSCMH1. RESULTS: CircSCMH1 levels were significantly decreased in the plasma of patients with acute ischemic stroke, offering significant power in predicting stroke outcomes. The decreased levels of circSCMH1 were further confirmed in the plasma and peri-infarct cortex of photothrombotic stroke mice. Beyond demonstrating proof-of-concept for an RNA drug delivery technology, we observed that circSCMH1 treatment improved functional recovery after stroke in both mice and monkeys, and we discovered that circSCMH1 enhanced the neuronal plasticity and inhibited glial activation and peripheral immune cell infiltration. CircSCMH1 binds mechanistically to the transcription factor MeCP2 (methyl-CpG binding protein 2), thereby releasing repression of MeCP2 target gene transcription. CONCLUSIONS: Rabies virus glycoprotein-circSCMH1-extracellular vesicles afford protection by promoting functional recovery in the rodent and the nonhuman primate ischemic stroke models. Our study presents a potentially widely applicable nucleotide drug delivery technology and demonstrates the basic mechanism of how circRNAs can be therapeutically exploited to improve poststroke outcomes.
Cardiac Energetics in Patients With Aortic Stenosis and Preserved Versus Reduced Ejection Fraction.
Peterzan MA, Clarke WT, Lygate CA … +13 more , Lake HA, Lau JYC, Miller JJ, Johnson E, Rayner JJ, Hundertmark MJ, Sayeed R, Petrou M, Krasopoulos G, Srivastava V, Neubauer S, Rodgers CT, Rider OJ
Circulation · 2020 Jun · PMID 32438845 · Full text
BACKGROUND: Why some but not all patients with severe aortic stenosis (SevAS) develop otherwise unexplained reduced systolic function is unclear. We investigate the hypothesis that reduced creatine kinase (CK) capacity a...
BACKGROUND: Why some but not all patients with severe aortic stenosis (SevAS) develop otherwise unexplained reduced systolic function is unclear. We investigate the hypothesis that reduced creatine kinase (CK) capacity and flux is associated with this transition. METHODS: We recruited 102 participants to 5 groups: moderate aortic stenosis (ModAS) (n=13), SevAS, left ventricular (LV) ejection fraction ≥55% (SevAS-preserved ejection fraction, n=37), SevAS, LV ejection fraction <55% (SevAS-reduced ejection fraction, n=15), healthy volunteers with nonhypertrophied hearts with normal systolic function (normal healthy volunteer, n=30), and patients with nonhypertrophied, non-pressure-loaded hearts with normal systolic function undergoing cardiac surgery and donating LV biopsy (non-pressure-loaded heart biopsy, n=7). All underwent cardiac magnetic resonance imaging and P magnetic resonance spectroscopy for myocardial energetics. LV biopsies (AS and non-pressure-loaded heart biopsy) were analyzed for CK total activity, CK isoforms, citrate synthase activity, and total creatine. Mitochondria-sarcomere diffusion distances were calculated by using serial block-face scanning electron microscopy. RESULTS: In the absence of failure, CK flux was lower in the presence of AS (by 32%, =0.04), driven primarily by reduction in phosphocreatine/ATP (by 17%, <0.001), with CK unchanged (=0.46). Although lowest in the SevAS-reduced ejection fraction group, CK flux was not different from the SevAS-preserved ejection fraction group (>0.99). Accompanying the fall in CK flux, total CK and citrate synthase activities and the absolute activities of mitochondrial-type CK and CK-MM isoforms were also lower (<0.02, all analyses). Median mitochondria-sarcomere diffusion distances correlated well with CK total activity (=0.86, =0.003). CONCLUSIONS: Total CK capacity is reduced in SevAS, with median values lowest in those with systolic failure, consistent with reduced energy supply reserve. Despite this, in vivo magnetic resonance spectroscopy measures of resting CK flux suggest that ATP delivery is reduced earlier, at the moderate AS stage, where LV function remains preserved. These findings show that significant energetic impairment is already established in moderate AS and suggest that a fall in CK flux is not by itself a necessary cause of transition to systolic failure. However, because ATP demands increase with AS severity, this could increase susceptibility to systolic failure. As such, targeting CK capacity and flux may be a therapeutic strategy to prevent and treat systolic failure in AS.
Lattice-Tip Focal Ablation Catheter That Toggles Between Radiofrequency and Pulsed Field Energy to Treat Atrial Fibrillation: A First-in-Human Trial.
Reddy VY, Anter E, Rackauskas G … +12 more , Peichl P, Koruth JS, Petru J, Funasako M, Minami K, Natale A, Jais P, Nakagawa H, Marinskis G, Aidietis A, Kautzner J, Neuzil P
Circ Arrhythm Electrophysiol · 2020 Jun · PMID 32383391 · Publisher ↗
BACKGROUND: The tissue selectivity of pulsed field ablation (PFA) provides safety advantages over radiofrequency ablation in treating atrial fibrillation. One-shot PFA catheters have been shown capable of performing pulm...
BACKGROUND: The tissue selectivity of pulsed field ablation (PFA) provides safety advantages over radiofrequency ablation in treating atrial fibrillation. One-shot PFA catheters have been shown capable of performing pulmonary vein isolation, but not flexible lesion sets such as linear lesions. A novel lattice-tip ablation catheter with a compressible 9-mm nitinol tip is able to deliver either focal radiofrequency ablation or PFA lesions, each in 2 to 5 s. METHODS: In a 3-center, single-arm, first-in-human trial, the 7.5F lattice catheter was used with a custom mapping system to treat paroxysmal or persistent atrial fibrillation. Toggling between energy sources, point-by-point pulmonary vein encirclement was performed using biphasic PFA posteriorly and either temperature-controlled irrigated radiofrequency ablation or PFA anteriorly (RF/PF or PF/PF, respectively). Linear lesions were created using either PFA or radiofrequency ablation. RESULTS: The 76-patient cohort included 55 paroxysmal and 21 persistent atrial fibrillation patients undergoing either RF/PF (40 patients) or PF/PF (36 patients) ablation. The pulmonary vein isolation therapy duration time (transpiring from first to last lesion) was 22.6±8.3 min/patient, with a mean of 50.1 RF/PF lesions/patient. Linear lesions included 14 mitral (4 RF/2 RF+PF/8 PF), 34 left atrium roof (12 RF/22 PF), and 44 cavotricuspid isthmus (36 RF/8 PF) lines, with therapy duration times of 5.1±3.5, 1.8±2.3, and 2.4±2.1 min/patient, respectively. All lesion sets were acutely successful, using 4.7±3.5 minutes of fluoroscopy. There were no device-related complications, including no strokes. Postprocedure esophagogastroduodenoscopy revealed minor mucosal thermal injury in 2 of 36 RF/PF and 0 of 24 PF/PF patients. Postprocedure brain magnetic resonance imaging revealed diffusion-weighted imaging+/fluid-attenuated inversion recovery- and diffusion-weighted imaging+/fluid-attenuated inversion recovery+ asymptomatic lesions in 5 and 3 of 51 patients, respectively. CONCLUSIONS: A novel lattice-tip catheter could safely and rapidly ablate atrial fibrillation using either a combined RF/PF approach (capitalizing on the safety of PFA and the years of experience with radiofrequency energy) or an entirely PF approach. Registration: URL: https://www.clinicaltrials.gov; Unique identifiers: NCT04141007 and NCT04194307.
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