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1.
JAMA ; 2021 Oct 11.
Artigo em Inglês | MEDLINE | ID: mdl-34633405

RESUMO

Importance: Acutely ill inpatients with COVID-19 typically receive antithrombotic therapy, although the risks and benefits of this intervention among outpatients with COVID-19 have not been established. Objective: To assess whether anticoagulant or antiplatelet therapy can safely reduce major adverse cardiopulmonary outcomes among symptomatic but clinically stable outpatients with COVID-19. Design, Setting, and Participants: The ACTIV-4B Outpatient Thrombosis Prevention Trial was designed as a minimal-contact, adaptive, randomized, double-blind, placebo-controlled trial to compare anticoagulant and antiplatelet therapy among 7000 symptomatic but clinically stable outpatients with COVID-19. The trial was conducted at 52 US sites between September 2020 and June 2021; final follow-up was August 5, 2021. Prior to initiating treatment, participants were required to have platelet count greater than 100 000/mm3 and estimated glomerular filtration rate greater than 30 mL/min/1.73 m2. Interventions: Random allocation in a 1:1:1:1 ratio to aspirin (81 mg orally once daily; n = 164), prophylactic-dose apixaban (2.5 mg orally twice daily; n = 165), therapeutic-dose apixaban (5 mg orally twice daily; n = 164), or placebo (n = 164) for 45 days. Main Outcomes and Measures: The primary end point was a composite of all-cause mortality, symptomatic venous or arterial thromboembolism, myocardial infarction, stroke, or hospitalization for cardiovascular or pulmonary cause. The primary analyses for efficacy and bleeding events were limited to participants who took at least 1 dose of trial medication. Results: On June 18, 2021, the trial data and safety monitoring board recommended early termination because of lower than anticipated event rates; at that time, 657 symptomatic outpatients with COVID-19 had been randomized (median age, 54 years [IQR, 46-59]; 59% women). The median times from diagnosis to randomization and from randomization to initiation of study treatment were 7 days and 3 days, respectively. Twenty-two randomized participants (3.3%) were hospitalized for COVID-19 prior to initiating treatment. Among the 558 patients who initiated treatment, the adjudicated primary composite end point occurred in 1 patient (0.7%) in the aspirin group, 1 patient (0.7%) in the 2.5-mg apixaban group, 2 patients (1.4%) in the 5-mg apixaban group, and 1 patient (0.7%) in the placebo group. The risk differences compared with placebo for the primary end point were 0.0% (95% CI not calculable) in the aspirin group, 0.7% (95% CI, -2.1% to 4.1%) in the 2.5-mg apixaban group, and 1.4% (95% CI, -1.5% to 5.0%) in the 5-mg apixaban group. Risk differences compared with placebo for bleeding events were 2.0% (95% CI, -2.7% to 6.8%), 4.5% (95% CI, -0.7% to 10.2%), and 6.9% (95% CI, 1.4% to 12.9%) among participants who initiated therapy in the aspirin, prophylactic apixaban, and therapeutic apixaban groups, respectively, although none were major. Findings inclusive of all randomized patients were similar. Conclusions and Relevance: Among symptomatic clinically stable outpatients with COVID-19, treatment with aspirin or apixaban compared with placebo did not reduce the rate of a composite clinical outcome. However, the study was terminated after enrollment of 9% of participants because of an event rate lower than anticipated. Trial Registration: ClinicalTrials.gov Identifier: NCT04498273.

3.
PLoS One ; 16(9): e0257184, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34570768

RESUMO

BACKGROUND: Coronary microvascular dysfunction (CMD) is prevalent in symptomatic women with ischemia but no obstructive coronary artery disease (INOCA). Urine albumin-creatinine ratio (UACR) is a measure of renal microvascular endothelial dysfunction. Both are predictors of adverse cardiovascular events. It is unknown if CMD could be a manifestation of a systemic process. We evaluated the relationship between renal microvascular dysfunction and CMD as measured by invasive coronary function testing (CFT). METHODS AND RESULTS: We measured urine albumin and creatinine to provide UACR in 152 women enrolled in the Women's Ischemia Syndrome Evaluation-Coronary Vascular Dysfunction (WISE-CVD) study (2008-2015) with suspected INOCA who underwent CFT. Invasive CFT measures of endothelial and non-endothelial dependent coronary microvascular function were obtained. Subjects were divided into those with detectable (≥20 mg/g) and undetectable urine albumin (<20 mg/g). The group mean age was 54 ± 11 years, with a moderate cardiac risk factor burden including low diabetes prevalence, and a mean UACR of 12 ± 55 mg/g (range 9.5-322.7 mg/g). Overall, coronary endothelial-dependent variables (change in coronary blood flow and coronary diameter in response to cold pressor testing) had significant inverse correlations with log UACR (r = -0.17, p = 0.05; r = -0.18, p = 0.03, respectively). CONCLUSIONS: Among women with INOCA and relatively low risk factor including diabetes burden, renal microvascular dysfunction, measured by UACR, is related to coronary endothelial-dependent CMD. These results suggest that coronary endothelial-dependent function may be a manifestation of a systemic process. Enhancing efferent arteriolar vasodilatation in both coronary endothelial-dependent function and renal microvascular dysfunction pose potential targets for investigation and treatment. CLINICAL TRIAL REGISTRATION: https://clinicaltrials.gov/ct2/show/NCT00832702.

4.
Artigo em Inglês | MEDLINE | ID: mdl-34553438

RESUMO

OBJECTIVES: To evaluate the prescription sequence symmetry analysis assumption regarding balance between marker drug (i.e., medication used to treat a drug-induced adverse event) initiation rates before and after initiation of an index drug (i.e., medication that is potentially associated with the drug-induced adverse event) in the absence of prescribing cascades, we used a well-described example of loop diuretic initiation to treat dihydropyridine calcium channel blockers (DH CCB)-induced edema. STUDY DESIGN AND SETTING: The University of Florida Health Integrated Data Repository from June 2011 and July 2018 was used to assess temporal prescribing of DH CCB and loop diuretics within the prescription sequence symmetry analysis framework. Validation of the prescribing cascade was performed via clinical expert chart review. RESULTS: Among patients without heart failure who were initiated on DH CCB, 26 and 64 loop diuretics initiators started within 360 days before versus after DH CCB initiation, respectively, resulting in an adjusted sequence ratio (aSR) of 2.27 (95% CI, 1.44-3.58). Overall, 35 (54.7%) patients were determined to have a prescribing cascade. Removing patients who experienced a prescribing cascade resulted in an aSR of 1.05, 95% CI 0.62-1.78). CONCLUSION: Loop diuretic initiation rates before and after DH CCB initiation for reasons other a prescribing cascade were similar, thus confirming the prescription sequence symmetry analysis assumption.

5.
Clin Cardiol ; 2021 Sep 16.
Artigo em Inglês | MEDLINE | ID: mdl-34528718

RESUMO

BACKGROUND: Coronary microvascular dysfunction (CMD) is associated with heart failure with preserved ejection fraction (HFpEF); however, pathophysiology is not well described. HYPOTHESIS: We hypothesized that CMD in women with suspected ischemia with no obstructive coronary artery disease (INOCA) is associated with cardiomyocyte dysfunction reflected by plasma levels of a cardiomyocyte calcium handling protein, cardiac bridge integrator 1 (cBIN1). METHODS: Women with suspected INOCA undergoing coronary function testing were included. Coronary flow reserve, vasodilation to nitroglycerin, change in coronary blood flow (ΔCBF), and vasodilation to acetylcholine (ΔAch) were evaluated. cBIN1 score (CS) levels in these women (n = 39) were compared to women with HFpEF (n = 20), heart failure with reduced ejection fraction (HFrEF) (n = 36), and reference controls (RC) (n = 50). Higher CS indicates cardiomyocyte tubule dysfunction. RESULTS: INOCA, HFpEF, and HFrEF women were older than RC (p < .05). Higher CS was associated with vasoconstriction to acetylcholine (r = -0.43, p = .011) with a trend towards lower ΔCBF (r = 0.30, p = .086). Higher CS was specific for ΔAch and ΔCBF but had limited sensitivity. INOCA women had higher CS than RC, but lower CS than HFpEF/HFrEF groups (p < .001). CONCLUSIONS: CS, a plasma biomarker indicating poor cardiomyocyte health, was higher in women with suspected INOCA as compared to RC, but lower than in women with HFpEF. Elevated CS in suspected INOCA patients represents an intermediate group between health and disease, supporting the hypothesis that CMD may progress to HFpEF. Larger prospective cohort studies are needed to confirm the pathophysiological relationship between cBIN1, CMD, and HFpEF.

6.
Am J Med ; 2021 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-34343507

RESUMO

Syndromes of cardiac ischemia with nonobstructive coronary arteries have been increasingly recognized as a clinical entity with heterogeneous clinical presentations, commonly encountered in women. Knowledge of pathophysiology and clinical risk factors is key to ensuring appropriate diagnostic evaluation and management for these often-neglected patients. In this review, we discuss the epidemiology, risk factors, and clinical presentations of these syndromes. We provide algorithms for diagnosis and management of these entities based on current scientific knowledge and highlight some of the key knowledge gaps and ongoing trials in this emerging field.

8.
Cardiovasc Res ; 2021 Aug 13.
Artigo em Inglês | MEDLINE | ID: mdl-34387303

RESUMO

Exogenous cell-based therapy has emerged as a promising new strategy to facilitate repair of hearts damaged by acute or chronic injury. However, the field of cell-based therapy is handicapped by the lack of standardized definitions and terminology, making comparisons across studies challenging. Even the term "stem cell therapy" is misleading because only a small percentage of cells derived from adult bone marrow, peripheral blood, or adipose tissue meets the accepted hematopoietic or developmental definition of stem cells. Furthermore, cells (stem or otherwise) are dynamic biological products, meaning that their surface marker expression, phenotypic and functional characteristics, and the products they secrete in response to their microenvironment can change. It is also important to point out that most surface markers are seldom specific for a cell type. In this article, we discuss the lack of consistency in the descriptive terminology used in cell-based therapies and offer guidelines aimed at standardizing nomenclature and definitions to improve communication among investigators and the general public.

9.
Clin Pharmacol Ther ; 110(3): 723-732, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34231218

RESUMO

We sought to identify genome-wide variants influencing antihypertensive drug response and adverse cardiovascular outcomes, utilizing data from four randomized controlled trials in the International Consortium for Antihypertensive Pharmacogenomics Studies (ICAPS). Genome-wide antihypertensive drug-single nucleotide polymorphism (SNP) interaction tests for four drug classes (ß-blockers, n = 9,195; calcium channel blockers (CCBs), n = 10,511; thiazide/thiazide-like diuretics, n = 3,516; ACE-inhibitors/ARBs, n = 2,559) and cardiovascular outcomes (incident myocardial infarction, stroke, or death) were analyzed among patients with hypertension of European ancestry. Top SNPs from the meta-analyses were tested for replication of cardiovascular outcomes in an independent Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) study (n = 21,267), blood pressure (BP) response in independent ICAPS studies (n = 1,552), and ethnic validation in African Americans from the Genetics of Hypertension Associated Treatment study (GenHAT; n = 5,115). One signal reached genome-wide significance in the ß-blocker-SNP interaction analysis (rs139945292, Interaction P = 1.56 × 10-8 ). rs139945292 was validated through BP response to ß-blockers, with the T-allele associated with less BP reduction (systolic BP response P = 6 × 10-4 , Beta = 3.09, diastolic BP response P = 5 × 10-3 , Beta = 1.53). The T-allele was also associated with increased adverse cardiovascular risk within the ß-blocker treated patients' subgroup (P = 2.35 × 10-4 , odds ratio = 1.57, 95% confidence interval = 1.23-1.99). The locus showed nominal replication in CHARGE, and consistent directional trends in ß-blocker treated African Americans. rs139945292 is an expression quantitative trait locus for the 50 kb upstream gene NTM (neurotrimin). No SNPs attained genome-wide significance for any other drugs classes. Top SNPs were located near CALB1 (CCB), FLJ367777 (ACE-inhibitor), and CES5AP1 (thiazide). The NTM region is associated with increased risk for adverse cardiovascular outcomes and less BP reduction in ß-blocker treated patients. Further investigation into this region is warranted.


Assuntos
Anti-Hipertensivos/uso terapêutico , Doenças Cardiovasculares/induzido quimicamente , Doenças Cardiovasculares/genética , Sistema Cardiovascular/efeitos dos fármacos , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/genética , Hipertensão/tratamento farmacológico , Afro-Americanos/genética , Idoso , Pressão Sanguínea/efeitos dos fármacos , Pressão Sanguínea/genética , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/etiologia , Feminino , Estudo de Associação Genômica Ampla/métodos , Humanos , Hipertensão/genética , Masculino , Pessoa de Meia-Idade , Testes Farmacogenômicos/métodos , Polimorfismo de Nucleotídeo Único/genética
10.
Am Heart J ; 241: 38-49, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34224684

RESUMO

BACKGROUND: Patients with refractory angina (RA) have poor quality of life and new therapies are needed. XC001 is a novel adenoviral vector expressing multiple isoforms of vascular endothelial growth factor (VEGF) promoting an enhanced local angiogenic effect. METHODS: The Epicardial Delivery of XC001 Gene Therapy for Refractory Angina Coronary Treatment (EXACT) trial is a 6-month (with 6-month extension) phase 1/2, first-in-human, multicenter, open-label, single-arm, dose-escalation study to evaluate the safety, tolerability, and preliminary efficacy of XC001 in patients with RA. The trial will enroll 33 patients in an initial (n = 12) ascending dose-escalation phase (1 × 109, 1 × 1010, 4 × 1010, and 1 × 1011 viral particles), followed by phase 2 (n = 21) assessing the highest tolerated dose. Patients must have stable Canadian Cardiovascular Society (CCS) class II-IV angina on maximally tolerated medical therapy without options for conventional revascularization, demonstrable ischemia on stress testing, and angina limiting exercise tolerance. XC001 will be delivered directly to ischemic myocardium via surgical transthoracic epicardial access. The primary outcome is safety via adverse event monitoring through 6 months. Efficacy assessments include difference from baseline to month 6 in time to 1 mm of ST segment depression, time to angina, and total exercise duration; myocardial blood flow at rest, and stress and coronary flow reserve by positron emission tomography; quality of life; CCS functional class; and angina frequency. CONCLUSIONS: The EXACT trial will determine whether direct intramyocardial administration of XC001 in patients with RA is safe and evaluate its effect on exercise tolerance, myocardial perfusion, angina and physical activity, informing future clinical investigation. CLINICAL TRIAL REGISTRATION: NCT04125732.

11.
Cells ; 10(6)2021 06 17.
Artigo em Inglês | MEDLINE | ID: mdl-34204247

RESUMO

Hypertension is associated with gut bacterial dysbiosis and gut pathology in animal models and people. Butyrate-producing gut bacteria are decreased in hypertension. RNA-seq analysis of gut colonic organoids prepared from spontaneously hypertensive rats (SHR) and normotensive Wistar Kyoto (WKY) rats was used to test the hypothesis that impaired interactions between the gut microbiome and gut epithelium are involved and that these would be remediated with butyrate supplementation. Gene expressions in immune responses including antigen presentation and antiviral pathways were decreased in the gut epithelium of the SHR in organoids and confirmed in vivo; these deficits were corrected by butyrate supplementation. Deficits in gene expression driving epithelial proliferation and differentiation were also observed in SHR. These findings highlight the importance of aligned interactions of the gut microbiome and gut immune responses to blood pressure homeostasis.

13.
Mayo Clin Proc ; 96(8): 2102-2113, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34144802

RESUMO

OBJECTIVE: To investigate the trend and outcomes of acute pulmonary embolism (PE) during pregnancy and puerperium using a large national database. PATIENTS AND METHODS: The National Inpatient Sample was queried to identify pregnancy-related hospitalizations in the United States from January 1, 2007, through September 30, 2015. Temporal trends in the rates of acute PE and in-hospital mortality rates were extracted. RESULTS: Among 37,524,314 hospitalizations, 6,333 patients (0.02%) had acute PE. The prevalence of comorbidities and risk factors such as hypertension, obesity, and smoking increased, but rates of acute PE did not change significantly (18.01 in 2007 vs 19.36 in 2015, per 100,000 hospitalizations, Ptrends=.21). Advanced therapies were used in a small number of women (systemic thrombolysis: 2.4%, surgical pulmonary embolectomy: 0.5%, and inferior vena cava filter in 8.3%). Rates of in-hospital mortality were almost 200-fold higher among those who had acute PE (29.3 vs 0.13, per 1000 pregnancy-related, P<.001). The rate of in-hospital mortality did not change among women with acute PE (2.6% in 2007 vs 2.5% in 2015, Ptrends=.74). CONCLUSION: In this contemporary analysis of pregnancy-related hospitalizations, acute PE was uncommon, but rates have not decreased over the past decade. Acute PE during pregnancy and puerperium was associated with high maternal mortality, and the rates of in-hospital mortality have not improved. Future studies to improve prevention and management of acute PE during pregnancy and puerperium are warranted.


Assuntos
Hospitalização/estatística & dados numéricos , Complicações Cardiovasculares na Gravidez/epidemiologia , Embolia Pulmonar/epidemiologia , Doença Aguda , Adulto , Feminino , Mortalidade Hospitalar/tendências , Humanos , Incidência , Período Pós-Parto , Gravidez , Complicações Cardiovasculares na Gravidez/terapia , Embolia Pulmonar/terapia , Estudos Retrospectivos , Fatores de Risco , Terapia Trombolítica/métodos , Estados Unidos/epidemiologia , Filtros de Veia Cava , Adulto Jovem
14.
PLoS Med ; 18(6): e1003599, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-34061831

RESUMO

BACKGROUND: Randomised evidence on the efficacy of blood pressure (BP)-lowering treatment to reduce cardiovascular risk in patients with atrial fibrillation (AF) is limited. Therefore, this study aimed to compare the effects of BP-lowering drugs in patients with and without AF at baseline. METHODS AND FINDINGS: The study was based on the resource provided by the Blood Pressure Lowering Treatment Trialists' Collaboration (BPLTTC), in which individual participant data (IPD) were extracted from trials with over 1,000 patient-years of follow-up in each arm, and that had randomly assigned patients to different classes of BP-lowering drugs, BP-lowering drugs versus placebo, or more versus less intensive BP-lowering regimens. For this study, only trials that had collected information on AF status at baseline were included. The effects of BP-lowering treatment on a composite endpoint of major cardiovascular events (stroke, ischaemic heart disease or heart failure) according to AF status at baseline were estimated using fixed-effect one-stage IPD meta-analyses based on Cox proportional hazards models stratified by trial. Furthermore, to assess whether the associations between the intensity of BP reduction and cardiovascular outcomes are similar in those with and without AF at baseline, we used a meta-regression. From the full BPLTTC database, 28 trials (145,653 participants) were excluded because AF status at baseline was uncertain or unavailable. A total of 22 trials were included with 188,570 patients, of whom 13,266 (7%) had AF at baseline. Risk of bias assessment showed that 20 trials were at low risk of bias and 2 trials at moderate risk. Meta-regression showed that relative risk reductions were proportional to trial-level intensity of BP lowering in patients with and without AF at baseline. Over 4.5 years of median follow-up, a 5-mm Hg systolic BP (SBP) reduction lowered the risk of major cardiovascular events both in patients with AF (hazard ratio [HR] 0.91, 95% confidence interval [CI] 0.83 to 1.00) and in patients without AF at baseline (HR 0.91, 95% CI 0.88 to 0.93), with no difference between subgroups. There was no evidence for heterogeneity of treatment effects by baseline SBP or drug class in patients with AF at baseline. The findings of this study need to be interpreted in light of its potential limitations, such as the limited number of trials, limitation in ascertaining AF cases due to the nature of the arrhythmia and measuring BP in patients with AF. CONCLUSIONS: In this meta-analysis, we found that BP-lowering treatment reduces the risk of major cardiovascular events similarly in individuals with and without AF. Pharmacological BP lowering for prevention of cardiovascular events should be recommended in patients with AF.


Assuntos
Anti-Hipertensivos/uso terapêutico , Fibrilação Atrial/epidemiologia , Pressão Sanguínea/efeitos dos fármacos , Doenças Cardiovasculares/prevenção & controle , Hipertensão/tratamento farmacológico , Idoso , Anti-Hipertensivos/efeitos adversos , Fibrilação Atrial/diagnóstico , Fibrilação Atrial/fisiopatologia , Doenças Cardiovasculares/diagnóstico , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/fisiopatologia , Feminino , Insuficiência Cardíaca/epidemiologia , Insuficiência Cardíaca/fisiopatologia , Insuficiência Cardíaca/prevenção & controle , Humanos , Hipertensão/diagnóstico , Hipertensão/epidemiologia , Hipertensão/fisiopatologia , Masculino , Pessoa de Meia-Idade , Isquemia Miocárdica/epidemiologia , Isquemia Miocárdica/fisiopatologia , Isquemia Miocárdica/prevenção & controle , Fatores de Proteção , Ensaios Clínicos Controlados Aleatórios como Assunto , Medição de Risco , Fatores de Risco , Acidente Vascular Cerebral/epidemiologia , Acidente Vascular Cerebral/fisiopatologia , Acidente Vascular Cerebral/prevenção & controle , Resultado do Tratamento
15.
Pharmacotherapy ; 41(9): 710-721, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34170559

RESUMO

STUDY OBJECTIVE: To assess the effectiveness of sacubitril/valsartan versus angiotensin receptor antagonist therapy for prevention of heart failure (HF)-related hospitalization and all-cause hospitalization in a large cohort of patients with heart failure with reduced ejection fraction (HFrEF). DESIGN: Retrospective cohort study. DATA SOURCE: IBM® MarketScan® research databases (2014-2018). PATIENTS: Patients aged 18 years or older with their first HFrEF hospitalization on or after January 1, 2015, who initiated sacubitril/valsartan or angiotensin receptor antagonist after hospital discharge. INTERVENTION: Sacubitril/Valsartan versus Angiotensin receptor antagonist. MEASUREMENTS AND MAIN RESULTS: The index date was the first sacubitril/valsartan or angiotensin receptor antagonist fill date. After 1 up to 3 propensity score matching, Cox proportional hazards regression was used with robust variance estimators to compare HF-related and all-cause hospitalizations between treatments. Subgroup and sensitivity analyses were conducted to assess the robustness of the main analysis. After propensity score matching, 1,088 sacubitril/valsartan and 2,839 angiotensin receptor antagonist new users were included. The crude incidence of HF-related hospitalization was 13 per 100 person-years for sacubitril/valsartan users and 18 per 100 person-years for angiotensin receptor antagonist users. Compared with angiotensin receptor antagonist use, sacubitril/valsartan use was associated with 27% lower risk of HF-related hospitalization (adjusted hazard ratio, 0.73; 95% confidence interval, 0.58-0.91; p = 0.006) and 31% lower risk of all-cause hospitalization (adjusted hazard ratio, 0.69; 95% confidence interval, 0.61-0.79; p < 0.001). Subgroup analyses revealed no significant heterogeneity, including subpopulations with chronic kidney disease or coronary artery disease. CONCLUSIONS: Compared with angiotensin receptor antagonists, sacubitril/valsartan was associated with lower risk of HF-related and all-cause hospitalizations. Our data suggest that, when added sequentially, sacubitril/valsartan should be the preferred initial agent over angiotensin receptor antagonists.

16.
Int J Cardiol ; 336: 1-7, 2021 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-34087335

RESUMO

The role of cardiac magnetic resonance (CMR) in identifying mechanisms for myocardial infarction with non-obstructed coronary arteries (MINOCA) is well established. Recent reports have highlighted the potentially key role of invasive management in this diagnostic process. Intravascular ultrasound (IVUS) and optical coherence tomography (OCT) allow precise evaluation of coronary anatomy, and assessment of coronary physiology in the catheter laboratory provides information on the hemodynamic significance of sub-critical atherosclerosis and on coronary microvascular dysfunction (CMD). We reviewed the evidence for the contribution of invasive diagnostic techniques in identifying provisional causes for MINOCA. Overall, among 82 studies including 8457 patients were selected. In the acute phase, 16 studies with IVUS or OCT (1207 patients) disclosed that plaque disruption and spontaneous coronary artery dissection had a pooled prevalence of 38% (95% confidence intervals (CI): 29% to 51%) and 16% (95% CI: 9% to 27%), respectively. In 18 studies, coronary function testing (1449 patients) showed a pooled prevalence of spontaneous and/or provoked epicardial coronary spasm of ~28% (95% CI:17% to 41%). In 3 studies (456 patients), the pooled prevalence of CMD was ~32% (95% CI: 20% to 49%). In the subacute phase, 42 CMR studies (5821 patients) showed that a pooled prevalence of myocarditis, takotsubo syndrome and cardiomyopathy of 26% (95% CI: 12% to 40%), 11% (95% CI: 5% to 25%), and 7% (95% CI: 1% to 19%), respectively. In 12 studies on thrombophilia screening (n = 834), the pooled prevalence of thrombotic disorder was ~11% (95% CI: 7%% to 25%). In conclusion, the pathophysiology of MINOCA can be established in the majority of cases using both invasive and non-invasive tools to provide direction for appropriate management.


Assuntos
Infarto do Miocárdio , Placa Aterosclerótica , Cardiomiopatia de Takotsubo , Angiografia Coronária , Vasos Coronários/diagnóstico por imagem , Humanos
17.
Int J Cardiol ; 338: 196-203, 2021 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-34126132

RESUMO

BACKGROUND: Ischemic heart disease and the resulting heart failure continue to carry high morbidity and mortality, and a breakthrough in our understanding of this disorder is needed. The adult spiny mouse (Acomys cahirinus) has evolved the remarkable capacity to regenerate full-thickness skin tissue, including microvasculature and cartilage, without fibrosis or scarring. We hypothesized that lack of scarring and resulting functional regeneration also applies to the adult Acomys heart. METHODS AND RESULTS: We compared responses of the Acomys heart to CD1 outbred Mus heart following acute left anterior descending coronary artery ligation to induce myocardial infarction. Both Acomys and Mus hearts showed decreased ejection fraction (EF) after ligation. However, Acomys hearts showed significant EF recovery to pre-ligation values over four weeks. Histological analysis showed comparable infarct area 24-h after ligation with a similar collateral flow in both species' hearts, but subsequently, Acomys displayed reduced infarct size, regenerated microvasculature, and increased cell proliferative activity in the infarcted area. CONCLUSIONS: These observations suggest that adult Acomys displays remarkable cardiac recovery properties after acute coronary artery occlusion and may be a useful model to understand functional recovery better. TRANSLATIONAL PERSPECTIVE: Adult Acomys provides a novel mammalian model to further investigate the cardioprotective and regenerative signaling mechanisms in adult mammals. This opens the door to breakthrough treatment strategies for the injured myocardium and help millions of patients with heart failure secondary to tissue injury with irreversible damage.


Assuntos
Regeneração , Pele , Adulto , Animais , Cicatriz , Fibrose , Humanos , Murinae , Pele/patologia
18.
Am Heart J ; 239: 27-37, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-33984318

RESUMO

BACKGROUND: Hypertension (HTN) is frequently linked with depression (DEP) in adults with cardiovascular disease (CVD), yet the underlying mechanism and successful management remain elusive. We approached this knowledge gap through the lens that humans are eukaryote-prokaryote "meta-organisms," such that cardiovascular disease dysregulation is a mosaic disorder involving dysbiosis of the gut. We hypothesized that patients diagnosed with hypertension plus depression harbor a unique gut microbial ecology with attending functional genomics engaged with their hosts' gut/brain axis physiology. METHODS: Stool microbiome DNA was analyzed by whole metagenome shotgun sequencing in 54 subjects parsed into cohorts diagnosed with HTN only (N = 18), DEP only (N = 7), DEP plus HTN (DEP-HTN) (N = 8), or reference subjects with neither HTN nor DEP (N = 21). A novel battery of machine-learning multivariate analyses of de-noised data yielded effect sizes and permutational covariance-based dissimilarities that significantly differentiated the cohorts (false discovery rate (FDR)-adjusted P ≤ .05); data clustering within 95% confidence interval). RESULTS: Metagenomic significant differences extricated the four cohorts. Data of the cohort exhibiting DEP-HTN were germane to the interplay of central control of blood pressure concomitant with the neuropathology of depressive disorders. DEP-HTN gut bacterial community ecology was defined by co-occurrence of Eubacterium siraeum, Alistipes obesi, Holdemania filiformis, and Lachnospiraceae bacterium 1.1.57FAA with Streptococcus salivariu. The corresponding microbial functional genomics of DEP-HTN engaged pathways degrading GABA and beneficial short chain fatty acids (SCFA), and are associated with enhanced sodium absorption and inflammasome induction. CONCLUSIONS: These data suggest a new putative endotype of hypertension, which we denote "depressive-hypertension" (DEP-HTN), for which we posit a model that is distinctive from either HTN alone or DEP alone. An "endotype" is a subtype of a heterogeneous pathophysiological mechanism. The DEP-HTN model incorporates a unique signature of microbial taxa and functional genomics with crosstalk that putatively intertwines host pathophysiology involving the gastrointestinal tract with disruptions in central control of blood pressure and mood. The DEP-HTN endotype model engages cardiology with gastroenterology and psychiatry, providing a proof-of-concept foundation to explore future treatments, diagnosis, and prevention of HTN-coupled mood disorders.


Assuntos
Afeto/fisiologia , Biota/genética , Depressão , Disbiose , Microbioma Gastrointestinal , Hipertensão , Adulto , Ciências Biocomportamentais , Depressão/diagnóstico , Depressão/metabolismo , Depressão/fisiopatologia , Disbiose/diagnóstico , Disbiose/fisiopatologia , Disbiose/psicologia , Fezes/microbiologia , Feminino , Microbioma Gastrointestinal/genética , Microbioma Gastrointestinal/fisiologia , Trato Gastrointestinal/microbiologia , Trato Gastrointestinal/fisiopatologia , Humanos , Hipertensão/diagnóstico , Hipertensão/metabolismo , Hipertensão/psicologia , Aprendizado de Máquina , Masculino , Redes e Vias Metabólicas , Metagenoma
19.
N Engl J Med ; 384(21): 1981-1990, 2021 05 27.
Artigo em Inglês | MEDLINE | ID: mdl-33999548

RESUMO

BACKGROUND: The appropriate dose of aspirin to lower the risk of death, myocardial infarction, and stroke and to minimize major bleeding in patients with established atherosclerotic cardiovascular disease is a subject of controversy. METHODS: Using an open-label, pragmatic design, we randomly assigned patients with established atherosclerotic cardiovascular disease to a strategy of 81 mg or 325 mg of aspirin per day. The primary effectiveness outcome was a composite of death from any cause, hospitalization for myocardial infarction, or hospitalization for stroke, assessed in a time-to-event analysis. The primary safety outcome was hospitalization for major bleeding, also assessed in a time-to-event analysis. RESULTS: A total of 15,076 patients were followed for a median of 26.2 months (interquartile range [IQR], 19.0 to 34.9). Before randomization, 13,537 (96.0% of those with available information on previous aspirin use) were already taking aspirin, and 85.3% of these patients were previously taking 81 mg of daily aspirin. Death, hospitalization for myocardial infarction, or hospitalization for stroke occurred in 590 patients (estimated percentage, 7.28%) in the 81-mg group and 569 patients (estimated percentage, 7.51%) in the 325-mg group (hazard ratio, 1.02; 95% confidence interval [CI], 0.91 to 1.14). Hospitalization for major bleeding occurred in 53 patients (estimated percentage, 0.63%) in the 81-mg group and 44 patients (estimated percentage, 0.60%) in the 325-mg group (hazard ratio, 1.18; 95% CI, 0.79 to 1.77). Patients assigned to 325 mg had a higher incidence of dose switching than those assigned to 81 mg (41.6% vs. 7.1%) and fewer median days of exposure to the assigned dose (434 days [IQR, 139 to 737] vs. 650 days [IQR, 415 to 922]). CONCLUSIONS: In this pragmatic trial involving patients with established cardiovascular disease, there was substantial dose switching to 81 mg of daily aspirin and no significant differences in cardiovascular events or major bleeding between patients assigned to 81 mg and those assigned to 325 mg of aspirin daily. (Funded by the Patient-Centered Outcomes Research Institute; ADAPTABLE ClinicalTrials.gov number, NCT02697916.).


Assuntos
Aspirina/administração & dosagem , Doenças Cardiovasculares/tratamento farmacológico , Inibidores da Agregação Plaquetária/administração & dosagem , Idoso , Aspirina/efeitos adversos , Aterosclerose/tratamento farmacológico , Doenças Cardiovasculares/mortalidade , Doenças Cardiovasculares/prevenção & controle , Feminino , Hemorragia/induzido quimicamente , Hospitalização , Humanos , Masculino , Adesão à Medicação/estatística & dados numéricos , Pessoa de Meia-Idade , Infarto do Miocárdio/epidemiologia , Infarto do Miocárdio/prevenção & controle , Inibidores da Agregação Plaquetária/efeitos adversos , Prevenção Secundária , Acidente Vascular Cerebral/epidemiologia , Acidente Vascular Cerebral/prevenção & controle
20.
Artigo em Inglês | MEDLINE | ID: mdl-33978865

RESUMO

Ischemic heart disease (IHD) is a leading global cause of ill-health and premature death. Clinical research into IHD is providing new insights into the pathophysiology, epidemiology and treatment of this condition. The major endotypes of IHD include coronary heart disease (CHD) and vasomotor disorders, including microvascular angina and vasospastic angina. Considering unselected patients presenting with stable chest pain, the pre-test probability of CHD is higher in men whereas the pre-test probability of a vasomotor disorder is higher in women. The diagnostic accuracy of diagnostic tests designed to assess coronary anatomy and disease and/or coronary vascular function (functional tests) differ for coronary endotypes. Clinical management should therefore be personalized and take account of sex-related factors. In this review, we consider the definitions of angina and myocardial ischemia. We then appraise the mechanistic links between myocardial ischemia and anginal symptoms and the relative merits of non-invasive and invasive diagnostic tests and related clinical management. Finally, we describe the rationale and importance of stratified medicine of IHD.

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