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1.
N Engl J Med ; 390(20): 1849-1861, 2024 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-38739079

RESUMO

BACKGROUND: One of the major determinants of exercise intolerance and limiting symptoms among patients with obstructive hypertrophic cardiomyopathy (HCM) is an elevated intracardiac pressure resulting from left ventricular outflow tract obstruction. Aficamten is an oral selective cardiac myosin inhibitor that reduces left ventricular outflow tract gradients by mitigating cardiac hypercontractility. METHODS: In this phase 3, double-blind trial, we randomly assigned adults with symptomatic obstructive HCM to receive aficamten (starting dose, 5 mg; maximum dose, 20 mg) or placebo for 24 weeks, with dose adjustment based on echocardiography results. The primary end point was the change from baseline to week 24 in the peak oxygen uptake as assessed by cardiopulmonary exercise testing. The 10 prespecified secondary end points (tested hierarchically) were change in the Kansas City Cardiomyopathy Questionnaire clinical summary score (KCCQ-CSS), improvement in the New York Heart Association (NYHA) functional class, change in the pressure gradient after the Valsalva maneuver, occurrence of a gradient of less than 30 mm Hg after the Valsalva maneuver, and duration of eligibility for septal reduction therapy (all assessed at week 24); change in the KCCQ-CSS, improvement in the NYHA functional class, change in the pressure gradient after the Valsalva maneuver, and occurrence of a gradient of less than 30 mm Hg after the Valsalva maneuver (all assessed at week 12); and change in the total workload as assessed by cardiopulmonary exercise testing at week 24. RESULTS: A total of 282 patients underwent randomization: 142 to the aficamten group and 140 to the placebo group. The mean age was 59.1 years, 59.2% were men, the baseline mean resting left ventricular outflow tract gradient was 55.1 mm Hg, and the baseline mean left ventricular ejection fraction was 74.8%. At 24 weeks, the mean change in the peak oxygen uptake was 1.8 ml per kilogram per minute (95% confidence interval [CI], 1.2 to 2.3) in the aficamten group and 0.0 ml per kilogram per minute (95% CI, -0.5 to 0.5) in the placebo group (least-squares mean between-group difference, 1.7 ml per kilogram per minute; 95% CI, 1.0 to 2.4; P<0.001). The results for all 10 secondary end points were significantly improved with aficamten as compared with placebo. The incidence of adverse events appeared to be similar in the two groups. CONCLUSIONS: Among patients with symptomatic obstructive HCM, treatment with aficamten resulted in a significantly greater improvement in peak oxygen uptake than placebo. (Funded by Cytokinetics; SEQUOIA-HCM ClinicalTrials.gov number, NCT05186818.).


Assuntos
Cardiomiopatia Hipertrófica , Fármacos Cardiovasculares , Teste de Esforço , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Benzilaminas , Miosinas Cardíacas/antagonistas & inibidores , Cardiomiopatia Hipertrófica/tratamento farmacológico , Cardiomiopatia Hipertrófica/fisiopatologia , Método Duplo-Cego , Tolerância ao Exercício/efeitos dos fármacos , Consumo de Oxigênio/efeitos dos fármacos , Uracila/análogos & derivados , Manobra de Valsalva , Obstrução do Fluxo Ventricular Externo/tratamento farmacológico , Obstrução do Fluxo Ventricular Externo/fisiopatologia , Obstrução do Fluxo Ventricular Externo/etiologia , Fármacos Cardiovasculares/farmacologia , Fármacos Cardiovasculares/uso terapêutico , Contração Miocárdica/efeitos dos fármacos , Contração Miocárdica/fisiologia , Administração Oral
2.
Circulation ; 149(7): 498-509, 2024 02 13.
Artigo em Inglês | MEDLINE | ID: mdl-37961906

RESUMO

BACKGROUND: Compared with men, women with hypertrophic cardiomyopathy (HCM) have a higher incidence of heart failure and worse outcomes. We investigated baseline clinical and echocardiographic characteristics and response to mavacamten among women compared with men in the EXPLORER-HCM study (Clinical Study to Evaluate Mavacamten [MYK-461] in Adults With Symptomatic Obstructive Hypertrophic Cardiomyopathy). METHODS: A prespecified post hoc analysis of sex from the blinded, randomized EXPLORER-HCM trial of mavacamten versus placebo in symptomatic patients with obstructive HCM was performed. Baseline characteristics were compared with t tests for continuous variables (expressed as mean values) and χ2 tests for categorical variables. Prespecified primary, secondary, and exploratory end points and echocardiographic measurements from baseline to end of treatment (week 30) were analyzed with ANCOVA for continuous end points and a generalized linear model with binomial distribution for binary end points, with adjustment for each outcome's baseline value, New York Heart Association class, ß-blocker use, and ergometer type. RESULTS: At baseline, women (n=102) were older (62 years versus 56 years; P<0.0001), had lower peak oxygen consumption (16.7 mL·kg-1·min-1 versus 21.3 mL·kg-1·min-1; P<0.0001), were more likely to be assigned New York Heart Association class III (42% versus 17%; P<0.0001), had worse health status (Kansas City Cardiomyopathy Questionnaire-Clinical Summary Score 64 versus 75; P<0.0001), and had higher baseline plasma NT-proBNP (N-terminal pro-B-type natriuretic peptide) levels (1704 ng/L versus 990 ng/L; P=0.004) than men (n=149). After 30 weeks of mavacamten treatment, similar improvements were observed in women and men in the primary composite end point (percentage difference on mavacamten versus placebo, 22% versus 19%, respectively; P=0.759) and in the secondary end points of change in postexercise left ventricular outflow tract gradient (-42.4 mm Hg versus -33.6 mm Hg; P=0.348), change in peak oxygen consumption (1.2 mL·kg-1·min-1 versus 1.6 mL·kg-1·min-1; P=0.633), and percentage achieving ≥1 New York Heart Association class improvement (41% versus 28%; P=0.254). However, women had greater improvement in health status (Kansas City Cardiomyopathy Questionnaire-Clinical Summary Score 14.8 versus 6.1; P=0.026) and in the exploratory end point of NT-proBNP levels (-1322 ng/L versus -649 ng/L; P=0.0008). CONCLUSIONS: Although at baseline women with symptomatic obstructive HCM enrolled in EXPLORER-HCM were older and had worse heart failure and health status than men, treatment with mavacamten resulted in similar improvements in the primary and most secondary EXPLORER-HCM end points and greater improvements in health status and NT-proBNP. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03470545.


Assuntos
Benzilaminas , Cardiomiopatia Hipertrófica , Uracila , Adulto , Feminino , Humanos , Masculino , Benzilaminas/uso terapêutico , Cardiomiopatia Hipertrófica/tratamento farmacológico , Insuficiência Cardíaca , Uracila/uso terapêutico , Uracila/análogos & derivados , Ensaios Clínicos Controlados Aleatórios como Assunto , Fatores Sexuais
3.
Circulation ; 149(22): 1717-1728, 2024 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-38583147

RESUMO

BACKGROUND: The impact of routine clinic use of patient-reported outcome (PRO) measures on clinical outcomes in patients with heart failure (HF) has not been well-characterized. We tested if clinic-based use of a disease-specific PRO improves patient-reported quality of life at 1 year. METHODS: The PRO-HF trial (Patient-Reported Outcome Measurement in Heart Failure Clinic) was an open-label, parallel, patient-level randomized clinical trial of routine PRO assessment or usual care at an academic HF clinic between August 30, 2021, and June 30, 2022, with 1 year of follow-up. In the PRO assessment arm, participants completed the Kansas City Cardiomyopathy Questionnaire-12 (KCCQ-12) at each HF clinic visit, and results were shared with their treating clinician. The usual care arm completed the KCCQ-12 at randomization and 1 year later, which was not shared with the treating clinician. The primary outcome was the KCCQ-12 overall summary score (OSS) between 12 and 15 months after randomization. Secondary outcomes included domains of the KCCQ-12, hospitalization and emergency department visit rates, HF medication therapy, clinic visit frequency, and testing rates. RESULTS: Across 17 clinicians, 1248 participants were enrolled and randomized to PRO assessment (n=624) or usual care (n=624). The median age was 63.9 years (interquartile range [IQR], 51.8-72.8), 38.9% were women, and the median baseline KCCQ-12 OSS was 82.3 (IQR, 58.3-94.8). Final KCCQ-12 (available in 87.9% of the PRO arm and 85.1% in usual care; P=0.16) median OSS were 87.5 (IQR, 68.8-96.9) in the PRO arm and 87.6 (IQR, 69.7-96.9) in the usual care arm with a baseline-adjusted mean difference of 0.2 ([95% CI, -1.7 to 2.0]; P=0.85). The results were consistent across prespecified subgroups. A post hoc analysis demonstrated a significant interaction with greater benefit among participants with a baseline KCCQ-12 OSS of 60 to 80 but not in less or more symptomatic participants. No significant differences were found in 1-year mortality, hospitalizations, emergency department visits, medication therapy, clinic follow-up, or testing rates between arms. CONCLUSIONS: Routine PRO assessment in HF clinic visits did not impact patient-reported quality of life or other clinical outcomes. Alternate strategies and settings for embedding PROs into routine clinical care should be tested. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT04164004.


Assuntos
Nível de Saúde , Insuficiência Cardíaca , Medidas de Resultados Relatados pelo Paciente , Qualidade de Vida , Humanos , Insuficiência Cardíaca/diagnóstico , Insuficiência Cardíaca/mortalidade , Insuficiência Cardíaca/terapia , Masculino , Feminino , Idoso , Pessoa de Meia-Idade
4.
N Engl J Med ; 387(17): 1569-1578, 2022 10 27.
Artigo em Inglês | MEDLINE | ID: mdl-36300973

RESUMO

BACKGROUND: Differences in the incidence of cardiopulmonary resuscitation (CPR) provided by bystanders contribute to survival disparities among persons with out-of-hospital cardiac arrest. It is critical to understand whether the incidence of bystander CPR in witnessed out-of-hospital cardiac arrests at home and in public settings differs according to the race or ethnic group of the person with cardiac arrest in order to inform interventions. METHODS: Within a large U.S. registry, we identified 110,054 witnessed out-of-hospital cardiac arrests during the period from 2013 through 2019. We used a hierarchical logistic regression model to analyze the incidence of bystander CPR in Black or Hispanic persons as compared with White persons with witnessed cardiac arrests at home and in public locations. We analyzed the overall incidence as well as the incidence according to neighborhood racial or ethnic makeup and income strata. Neighborhoods were classified as predominantly White (>80% of residents), majority Black or Hispanic (>50% of residents), or integrated, and as high income (an annual median household income of >$80,000), middle income ($40,000-$80,000), or low income (<$40,000). RESULTS: Overall, 35,469 of the witnessed out-of-hospital cardiac arrests (32.2%) occurred in Black or Hispanic persons. Black and Hispanic persons were less likely to receive bystander CPR at home (38.5%) than White persons (47.4%) (adjusted odds ratio, 0.74; 95% confidence interval [CI], 0.72 to 0.76) and less likely to receive bystander CPR in public locations than White persons (45.6% vs. 60.0%) (adjusted odds ratio, 0.63; 95% CI, 0.60 to 0.66). The incidence of bystander CPR among Black and Hispanic persons was less than that among White persons not only in predominantly White neighborhoods at home (adjusted odds ratio, 0.82; 95% CI, 0.74 to 0.90) and in public locations (adjusted odds ratio, 0.68; 95% CI, 0.60 to 0.75) but also in majority Black or Hispanic neighborhoods at home (adjusted odds ratio, 0.79; 95% CI, 0.75 to 0.83) and in public locations (adjusted odds ratio, 0.63; 95% CI, 0.59 to 0.68) and in integrated neighborhoods at home (adjusted odds ratio, 0.78; 95% CI, 0.74 to 0.81) and in public locations (adjusted odds ratio, 0.73; 95% CI, 0.68 to 0.77). Similarly, across all neighborhood income strata, the frequency of bystander CPR at home and in public locations was lower among Black and Hispanic persons with out-of-hospital cardiac arrest than among White persons. CONCLUSIONS: In witnessed out-of-hospital cardiac arrest, Black and Hispanic persons were less likely than White persons to receive potentially lifesaving bystander CPR at home and in public locations, regardless of the racial or ethnic makeup or income level of the neighborhood where the cardiac arrest occurred. (Funded by the National Heart, Lung, and Blood Institute.).


Assuntos
População Negra , Reanimação Cardiopulmonar , Hispânico ou Latino , Parada Cardíaca Extra-Hospitalar , População Branca , Humanos , Reanimação Cardiopulmonar/estatística & dados numéricos , Serviços Médicos de Emergência/estatística & dados numéricos , Hispânico ou Latino/estatística & dados numéricos , Renda/estatística & dados numéricos , Parada Cardíaca Extra-Hospitalar/epidemiologia , Parada Cardíaca Extra-Hospitalar/etnologia , Parada Cardíaca Extra-Hospitalar/terapia , Características de Residência/estatística & dados numéricos , Fatores Raciais/estatística & dados numéricos , Incidência , Estados Unidos/epidemiologia , Sistema de Registros/estatística & dados numéricos , População Branca/estatística & dados numéricos , População Negra/estatística & dados numéricos
5.
Eur Heart J ; 45(36): 3735-3747, 2024 Sep 29.
Artigo em Inglês | MEDLINE | ID: mdl-39101625

RESUMO

BACKGROUND AND AIMS: The aim of this study was to determine the prognostic value of coronary computed tomography angiography (CCTA)-derived atherosclerotic plaque analysis in ISCHEMIA. METHODS: Atherosclerosis imaging quantitative computed tomography (AI-QCT) was performed on all available baseline CCTAs to quantify plaque volume, composition, and distribution. Multivariable Cox regression was used to examine the association between baseline risk factors (age, sex, smoking, diabetes, hypertension, ejection fraction, prior coronary disease, estimated glomerular filtration rate, and statin use), number of diseased vessels, atherosclerotic plaque characteristics determined by AI-QCT, and a composite primary outcome of cardiovascular death or myocardial infarction over a median follow-up of 3.3 (interquartile range 2.2-4.4) years. The predictive value of plaque quantification over risk factors was compared in an area under the curve (AUC) analysis. RESULTS: Analysable CCTA data were available from 3711 participants (mean age 64 years, 21% female, 79% multivessel coronary artery disease). Amongst the AI-QCT variables, total plaque volume was most strongly associated with the primary outcome (adjusted hazard ratio 1.56, 95% confidence interval 1.25-1.97 per interquartile range increase [559 mm3]; P = .001). The addition of AI-QCT plaque quantification and characterization to baseline risk factors improved the model's predictive value for the primary outcome at 6 months (AUC 0.688 vs. 0.637; P = .006), at 2 years (AUC 0.660 vs. 0.617; P = .003), and at 4 years of follow-up (AUC 0.654 vs. 0.608; P = .002). The findings were similar for the other reported outcomes. CONCLUSIONS: In ISCHEMIA, total plaque volume was associated with cardiovascular death or myocardial infarction. In this highly diseased, high-risk population, enhanced assessment of atherosclerotic burden using AI-QCT-derived measures of plaque volume and composition modestly improved event prediction.


Assuntos
Angiografia por Tomografia Computadorizada , Angiografia Coronária , Doença da Artéria Coronariana , Placa Aterosclerótica , Humanos , Feminino , Masculino , Pessoa de Meia-Idade , Placa Aterosclerótica/diagnóstico por imagem , Angiografia Coronária/métodos , Doença da Artéria Coronariana/diagnóstico por imagem , Idoso , Prognóstico , Fatores de Risco de Doenças Cardíacas , Fatores de Risco , Infarto do Miocárdio/epidemiologia , Infarto do Miocárdio/etiologia , Isquemia Miocárdica
6.
Circulation ; 148(3): 220-228, 2023 07 18.
Artigo em Inglês | MEDLINE | ID: mdl-37191040

RESUMO

BACKGROUND: Health status outcomes, including symptoms, function, and quality of life, are worse for Black compared with White patients with heart failure. Sodium-glucose cotransporter 2 inhibitors (SGLT2is) reduce cardiovascular mortality and improve health status in patients with heart failure, but whether the health status benefit of SGLT2is is similar across races is not established. The objective of this study was to compare the treatment effect of SGLT2is (versus placebo) on health status for Black compared with White patients with heart failure. METHODS: We combined patient-level data from 3 randomized clinical trials of SGLT2is: DEFINE-HF (Dapagliflozin Effect on Symptoms and Biomarkers in Patients With Heart Failure; n=263), PRESERVED-HF (Dapagliflozin in Preserved Ejection Fraction Heart Failure; n=324), and CHIEF-HF (A Study on Impact of Canagliflozin on Health Status, Quality of Life, and Functional Status in Heart Failure; n=448). These 3 United States-based trials enrolled a substantial proportion of Black patients, and each used the Kansas City Cardiomyopathy Questionnaire (KCCQ) to measure health status at baseline and after 12 weeks of treatment. Among 1035 total participants, selecting self-identified Black and White patients with complete information yielded a final analytic cohort of 935 patients. The primary endpoint was KCCQ Clinical Summary score. Twelve-week change in KCCQ with SGLT2is versus placebo was compared between Black and White patients by testing the interaction between race and treatment using multivariable linear regression models adjusted for trial, baseline KCCQ (as a restricted cubic spline), race, and treatment. The data that support the findings of this study are available from the corresponding author upon reasonable request. RESULTS: Among 935 participants, 236 (25%) self-identified as Black, and 469 (50.2%) were treated with an SGLT2i. Treatment with an SGLT2i, compared with placebo, resulted in KCCQ Clinical Summary score improvements at 12 weeks of +4.0 points (95% CI, 1.7-6.3; P=0.0007) in White patients and +4.7 points (95% CI, 0.7-8.7; P=0.02) in Black patients, with no significant interaction by race and treatment (P=0.76). Other KCCQ scales showed similar results. CONCLUSIONS: Treatment with an SGLT2i resulted in consistent and significant improvements in health status for both Black and White patients with heart failure.


Assuntos
Insuficiência Cardíaca , Qualidade de Vida , Humanos , Fatores Raciais , Insuficiência Cardíaca/diagnóstico , Insuficiência Cardíaca/tratamento farmacológico , Glucose , Sódio , Volume Sistólico , Ensaios Clínicos Controlados Aleatórios como Assunto
7.
Circulation ; 147(1): 8-19, 2023 01 03.
Artigo em Inglês | MEDLINE | ID: mdl-36335918

RESUMO

BACKGROUND: The ISCHEMIA trial (International Study of Comparative Health Effectiveness With Medical and Invasive Approaches) compared an initial invasive versus an initial conservative management strategy for patients with chronic coronary disease and moderate or severe ischemia, with no major difference in most outcomes during a median of 3.2 years. Extended follow-up for mortality is ongoing. METHODS: ISCHEMIA participants were randomized to an initial invasive strategy added to guideline-directed medical therapy or a conservative strategy. Patients with moderate or severe ischemia, ejection fraction ≥35%, and no recent acute coronary syndromes were included. Those with an unacceptable level of angina were excluded. Extended follow-up for vital status is being conducted by sites or through central death index search. Data obtained through December 2021 are included in this interim report. We analyzed all-cause, cardiovascular, and noncardiovascular mortality by randomized strategy, using nonparametric cumulative incidence estimators, Cox regression models, and Bayesian methods. Undetermined deaths were classified as cardiovascular as prespecified in the trial protocol. RESULTS: Baseline characteristics for 5179 original ISCHEMIA trial participants included median age 65 years, 23% women, 16% Hispanic, 4% Black, 42% with diabetes, and median ejection fraction 0.60. A total of 557 deaths accrued during a median follow-up of 5.7 years, with 268 of these added in the extended follow-up phase. This included a total of 343 cardiovascular deaths, 192 noncardiovascular deaths, and 22 unclassified deaths. All-cause mortality was not different between randomized treatment groups (7-year rate, 12.7% in invasive strategy, 13.4% in conservative strategy; adjusted hazard ratio, 1.00 [95% CI, 0.85-1.18]). There was a lower 7-year rate cardiovascular mortality (6.4% versus 8.6%; adjusted hazard ratio, 0.78 [95% CI, 0.63-0.96]) with an initial invasive strategy but a higher 7-year rate of noncardiovascular mortality (5.6% versus 4.4%; adjusted hazard ratio, 1.44 [95% CI, 1.08-1.91]) compared with the conservative strategy. No heterogeneity of treatment effect was evident in prespecified subgroups, including multivessel coronary disease. CONCLUSIONS: There was no difference in all-cause mortality with an initial invasive strategy compared with an initial conservative strategy, but there was lower risk of cardiovascular mortality and higher risk of noncardiovascular mortality with an initial invasive strategy during a median follow-up of 5.7 years. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT04894877.


Assuntos
Síndrome Coronariana Aguda , Doença da Artéria Coronariana , Humanos , Feminino , Idoso , Masculino , Tratamento Conservador , Teorema de Bayes , Doença da Artéria Coronariana/terapia , Síndrome Coronariana Aguda/terapia , Resultado do Tratamento
8.
J Card Fail ; 2024 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-39349160

RESUMO

BACKGROUND: A primary goal of treating patients with obstructive hypertrophic cardiomyopathy (oHCM) is to improve their symptoms, function, and quality of life. While the psychometric properties of the 23-item Kansas City Cardiomyopathy Questionnaire (KCCQ-23) have been described in oHCM, they have not been assessed for the shorter 12-item version (KCCQ-12), which is increasingly used in clinical practice. METHODS AND RESULTS: Using data from the EXPLORER-HCM trial, the psychometric properties of the KCCQ-12 were evaluated. The KCCQ-12 domain and summary scores had moderate correlations with the most relevant clinical (New York Heart Association class, exercise duration, peak oxygen consumption) and patient-reported measures (EQ-5D-5L visual analog scale, Work Productivity and Activity Impairment [WPAI] questionnaire, and Hypertrophic Cardiomyopathy Symptom Questionnaire [HCMSQ]). KCCQ-12 domain scores had strong internal consistency and test-retest reliability, demonstrated significant and proportional changes with different magnitudes of clinical change (assessed with the patient global impression of change and patient impression of severity), and demonstrated close equivalence to the KCCQ-23 scores. CONCLUSIONS: The KCCQ-12 demonstrated good psychometric performance for patients with oHCM, comparable to that of the KCCQ-23, supporting its use in clinical practice to care for patients with oHCM.

9.
J Card Fail ; 2024 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-39349158

RESUMO

BACKGROUND: In order to identify candidacy and treatment response for patients with obstructive hypertrophic cardiomyopathy (oHCM), clinicians need an accurate means of assessing symptoms, function, and quality of life. While the New York Heart Association (NYHA) Classification is most often used, the Kansas City Cardiomyopathy Questionnaire (KCCQ-23) is more accurate and sensitive to change, although less familiar to practicing clinicians. To support interpreting the KCCQ, we describe cross-sectional and changes in KCCQ scores in the context of the NYHA. METHODS: Participants from the EXPLORER-HCM trial (NCT03470545) completed the KCCQ-23 and clinicians assigned NYHA classes at study visits. Participants were included if they had baseline and week 30 data for cross-sectional and longitudinal changes. Median KCCQ-23 scores were compared by NYHA class at baseline and week 30 and by change in NYHA class from baseline to week 30. RESULTS: Cross-sectionally, the KCCQ-23 Overall Summary Scores (KCCQ-23 OSS) and Clinical Summary Scores (KCCQ-23 CSS) had an inverse relationship with NYHA at baseline and 30 weeks, with marked variations in KCCQ-23 scores among patients assigned to the same NYHA class. When improving from NYHA class II to I, the median changes in KCCQ-23 OSS and KCCQ-23 CSS were 10 (IQR 4, 22) and 8 (IQR 2, 20), respectively. The changes were larger when improving from NYHA class III to II and from NYHA class III to I. CONCLUSION: KCCQ-23 scores are inversely related to NYHA classes, with significant variability within classes. Changes in scores are not linear, suggest greater differences when patients move between NYHA Class II and III than Class I and II. These insights may help clinicians better understand cross-sectional and changes in KCCQ scores.

10.
J Card Fail ; 2024 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-39299541

RESUMO

BACKGROUND: Optimal management of outpatients with heart failure (HF) requires serially updating the estimates of their risk for adverse clinical outcomes to guide treatment. Patient-reported outcomes (PROs) are becoming increasingly used in clinical care. The purpose of this study was to determine whether the inclusion of PROs can improve the risk prediction for HF hospitalization and death in ambulatory patients with HF. METHODS AND RESULTS: We included consecutive patients with HF with reduced ejection fraction (HFrEF) and HF with preserved EF (HFpEF) seen in a HF clinic between 2015 and 2019 who completed PROs as part of routine care. Cox regression with a least absolute shrinkage and selection operator regularization and gradient boosting machine analyses were used to estimate risk for a combined outcome of HF hospitalization, heart transplant, left ventricular assist device implantation, or death. The performance of the prediction models was evaluated with the time-dependent concordance index (Cτ). Among 1165 patients with HFrEF (mean age 59.1 ± 16.1, 68% male), the median follow-up was 487 days. Among 456 patients with HFpEF (mean age 64.2 ± 16.0 years, 55% male) the median follow-up was 494 days. Gradient boosting regression that included PROs had the best prediction performance - Cτ 0.73 for patients with HFrEF and 0.74 in patients with HFpEF, and showed very good stratification of risk by time to event analysis by quintile of risk. The Kansas City Cardiomyopathy Questionnaire overall summary score, visual analogue scale and Patient Reported Outcomes Measurement Information System dimensions of satisfaction with social roles and physical function had high variable importance measure in the models. CONCLUSIONS: PROs improve risk prediction in both HFrEF and HFpEF, independent of traditional clinical factors. Routine assessment of PROs and leveraging the comprehensive data in the electronic health record in routine clinical care could help more accurately assess risk and support the intensification of treatment in patients with HF.

11.
J Vasc Surg ; 79(6): 1473-1482.e5, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38266885

RESUMO

BACKGROUND: As a key treatment goal for patients with symptomatic peripheral artery disease (PAD), improving health status has also become an important end point for clinical trials and performance-based care. An understanding of patient factors associated with 1-year PAD health status is lacking in patients with PAD. METHODS: The health status of 1073 consecutive patients with symptomatic PAD in the international multicenter PORTRAIT (Patient-Centered Outcomes Related to Treatment Practices in Peripheral Arterial Disease: Investigating Trajectories) registry was measured at baseline and 1 year with the Peripheral Artery Questionnaire (PAQ). The association of 47 patient characteristics with 1-year PAQ scores was assessed using a random forest algorithm. Variables of clinical significance were retained and included in a hierarchical multivariable linear regression model predicting 1-year PAQ summary scores. RESULTS: The mean age of patients was 67.7 ± 9.3 years, and 37% were female. Variables with the highest importance ranking in predicting 1-year PAQ summary score were baseline PAQ summary score, Patient Health Questionnaire-8 depression score, Generalized Anxiety Disorder-2 anxiety score, new onset symptom presentation, insurance status, current or prior diagnosis of depression, low social support, initial invasive treatment, duration of symptoms, and race. The addition of 19 clinical variables in an extended model marginally improved the explained variance in 1-year health status (from R2 0.312 to 0.335). CONCLUSIONS: Patients' 1-year PAD-specific health status, as measured by the PAQ, can be predicted from 10 mostly psychosocial and socioeconomic patient characteristics including depression, anxiety, insurance status, social support, and symptoms. These characteristics should be validated and tested in other PAD cohorts so that this model can inform risk adjustment and prediction of PAD health status in comparative effectiveness research and performance-based care.


Assuntos
Nível de Saúde , Claudicação Intermitente , Doença Arterial Periférica , Sistema de Registros , Determinantes Sociais da Saúde , Humanos , Feminino , Masculino , Idoso , Claudicação Intermitente/diagnóstico , Claudicação Intermitente/terapia , Claudicação Intermitente/psicologia , Claudicação Intermitente/epidemiologia , Doença Arterial Periférica/diagnóstico , Doença Arterial Periférica/terapia , Doença Arterial Periférica/psicologia , Doença Arterial Periférica/epidemiologia , Pessoa de Meia-Idade , Fatores de Tempo , Fatores de Risco , Inquéritos e Questionários , Saúde Mental , Fatores Socioeconômicos , Estudos Prospectivos
12.
Curr Opin Cardiol ; 39(6): 478-484, 2024 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-39254647

RESUMO

PURPOSE OF REVIEW: We review the limited available evidence informing coronary revascularization decisions in women and minorities, and introduce the RECHARGE trial program, which consists of two separate but integrated parallel multicenter, randomized trials comparing coronary artery bypass grafting (CABG) to percutaneous coronary intervention (PCI), one exclusively enrolling women (RECHARGE:Women) and one exclusively enrolling Black or Hispanic patients (RECHARGE:Minorities). RECENT FINDINGS: The extensive evidence base supporting coronary revascularization suffers from under-representation of women, minorities and minoritized populations, and the use of heterogeneous primary composite outcomes whose components have varying strengths of association with prognosis and quality-of-life (QOL). In RECHARGE, participants will be followed for up to 10 years, with QOL assessments at baseline, 30 days, 3 months, every 6 months for 3 years, and annually thereafter. The primary endpoint is the hierarchical composite of time to all-cause mortality, time-averaged change from baseline in the physical component of the SF-12v2 physical summary score, and time-averaged change from baseline in the mental component of the SF12v2 summary score, evaluated using a win ratio. Independently adjudicated major adverse cardiovascular and noncardiovascular events and disease-specific QoL will be secondary endpoints. SUMMARY: The RECHARGE trials are the first revascularization trials to enroll exclusively women and minority patients and to use patient-centered outcomes as their primary outcome.


Assuntos
Intervenção Coronária Percutânea , Humanos , Feminino , Intervenção Coronária Percutânea/métodos , Doença da Artéria Coronariana/cirurgia , Doença da Artéria Coronariana/terapia , Grupos Minoritários , Ensaios Clínicos Controlados Aleatórios como Assunto , Ponte de Artéria Coronária , Qualidade de Vida , Revascularização Miocárdica/métodos
13.
Vasc Med ; : 1358863X241274758, 2024 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-39319857

RESUMO

BACKGROUND: Healthcare utilization for patients with peripheral artery disease (PAD) is high, but stratifying patients' risk of hospitalization at initial evaluation is challenging. We examined the association between health status at PAD presentation and risk of (1) combined all-cause hospital admissions and emergency department (ED) visits and (2) all-cause hospital admissions. METHODS: Patients with claudication enrolled at US sites in the PORTRAIT registry were included. Health status was assessed using the Peripheral Artery Questionnaire (PAQ), a PAD-specific patient-reported outcome measure. Crude overall and cause-specific hospital admissions and ED visits were reported by PAQ overall summary score (PAQ-OS) ranges (0-24, 25-49, 50-74, and 75-100). Kaplan-Meier survival and unadjusted and adjusted Cox proportional hazards models examined the association between baseline PAQ scores and (1) combined all-cause hospital admissions or ED visits and (2) all-cause hospital admissions over 12 months. RESULTS: Of 796 patients, 349 (44%) had a hospital admission or ED visit over 12 months. Patients in the lowest (PAQ-OS = 0-24) versus the highest range (PAQ-OS = 75-100) had higher rates of 12-month (53.3% vs 22.4%) hospital admission and ED visits. In the adjusted model, each 10-point decrease in PAQ-OS was associated with a higher risk of all-cause hospital admission and ED visits (HR = 1.1, 95% CI 1.1-1.2, p < 0.0010) and all-cause hospital admission (HR = 1.1, 95% CI 1.1-1.2, p < 0.0010) at 12 months. CONCLUSION: PAD-specific health status is associated with an increased risk of healthcare utilization. Baseline health status may help stratify risk in patients with PAD, although replication and further validation of results are necessary.

14.
Eur Heart J ; 44(21): 1890-1909, 2023 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-37098746

RESUMO

Conventional randomized controlled trials (RCTs) can be expensive, time intensive, and complex to conduct. Trial recruitment, participation, and data collection can burden participants and research personnel. In the past two decades, there have been rapid technological advances and an exponential growth in digitized healthcare data. Embedding RCTs, including cardiovascular outcome trials, into electronic health record systems or registries may streamline screening, consent, randomization, follow-up visits, and outcome adjudication. Moreover, wearable sensors (i.e. health and fitness trackers) provide an opportunity to collect data on cardiovascular health and risk factors in unprecedented detail and scale, while growing internet connectivity supports the collection of patient-reported outcomes. There is a pressing need to develop robust mechanisms that facilitate data capture from diverse databases and guidance to standardize data definitions. Importantly, the data collection infrastructure should be reusable to support multiple cardiovascular RCTs over time. Systems, processes, and policies will need to have sufficient flexibility to allow interoperability between different sources of data acquisition. Clinical research guidelines, ethics oversight, and regulatory requirements also need to evolve. This review highlights recent progress towards the use of routinely generated data to conduct RCTs and discusses potential solutions for ongoing barriers. There is a particular focus on methods to utilize routinely generated data for trials while complying with regional data protection laws. The discussion is supported with examples of cardiovascular outcome trials that have successfully leveraged the electronic health record, web-enabled devices or administrative databases to conduct randomized trials.


Assuntos
Doenças Cardiovasculares , Registros Eletrônicos de Saúde , Dados de Saúde Coletados Rotineiramente , Humanos , Ensaios Clínicos Controlados Aleatórios como Assunto
15.
Circulation ; 146(20): e286-e297, 2022 11 15.
Artigo em Inglês | MEDLINE | ID: mdl-36252117

RESUMO

Peripheral artery disease (PAD) is chronic in nature, and individualized chronic disease management is a central focus of care. To accommodate this reality, tools to measure the impact and quality of the PAD care delivered are necessary. Patient-reported outcomes (PROs) and instruments to measure them, that is, PRO measures, have been well studied in the research and clinical trial context, but a shift toward integrating them into clinical practice has yet to take place. A framework to use PRO measures as indicators of the quality of PAD care delivered, that is, PRO performance measures (PRO-PMs), is provided in this scientific statement. Measurement goals to consider by PAD clinical phenotypes are provided, as well as an overview of potential benefits of adopting PRO-PMs in the clinical practice of PAD care, including reducing unwanted variability and promoting health equity. A central discussion with considerations for risk adjustment of PRO-PMs, individualized PAD care, and the need for patient engagement strategies is offered. Furthermore, necessary conditions in terms of required competencies and training to handle PRO-PM data are discussed because the interpretation and handling of these data come with great responsibility and consequences for designing care that adopts a broader framework of risk that goes beyond the inclusion of biomedical variables. To conclude, health system perspectives and an agenda to reach the next steps in the implementation of PRO-PMs in PAD care are offered.


Assuntos
American Heart Association , Doença Arterial Periférica , Humanos , Estados Unidos , Medidas de Resultados Relatados pelo Paciente , Doença Arterial Periférica/diagnóstico , Doença Arterial Periférica/terapia , Participação do Paciente , Nível de Saúde
16.
Circulation ; 145(17): 1294-1307, 2022 04 26.
Artigo em Inglês | MEDLINE | ID: mdl-35259918

RESUMO

BACKGROUND: ISCHEMIA (International Study of Comparative Health Effectiveness with Medical and Invasive Approaches) compared an initial invasive treatment strategy (INV) with an initial conservative strategy in 5179 participants with chronic coronary disease and moderate or severe ischemia. The ISCHEMIA research program included a comprehensive quality-of-life (QOL) substudy. METHODS: In 1819 participants (907 INV, 912 conservative strategy), we collected a battery of disease-specific and generic QOL instruments by structured interviews at baseline; at 3, 12, 24, and 36 months postrandomization; and at study closeout. Assessments included angina-related QOL (19-item Seattle Angina Questionnaire), generic health status (EQ-5D), depressive symptoms (Patient Health Questionnaire-8), and, for North American patients, cardiac functional status (Duke Activity Status Index). RESULTS: Median age was 67 years, 19.2% were female, and 15.9% were non-White. The estimated mean difference for the 19-item Seattle Angina Questionnaire Summary score favored INV (1.4 points [95% CI, 0.2-2.5] over all follow-up). No differences were observed in patients with rare/absent baseline angina (SAQ Angina Frequency score >80). Among patients with more frequent angina at baseline (SAQ Angina Frequency score <80, 744 patients, 41%), those randomly assigned to INV had a mean 3.7-point higher 19-item Seattle Angina Questionnaire Summary score than conservative strategy (95% CI, 1.6-5.8) with consistent effects across SAQ subscales: Physical Limitations 3.2 points (95% CI, 0.2-6.1), Angina Frequency 3.2 points (95% CI, 1.2-5.1), Quality of Life/Health Perceptions 5.3 points (95% CI, 2.8-7.8). For the Duke Activity Status Index, no difference was estimated overall by treatment, but in patients with baseline SAQ Angina Frequency scores <80, Duke Activity Status Index scores were higher for INV (3.2 points [95% CI, 0.6-5.7]), whereas patients with rare/absent baseline angina showed no treatment-related differences. Moderate to severe depression was infrequent at randomization (11.5%-12.8%) and was unaffected by treatment assignment. CONCLUSIONS: In the ISCHEMIA comprehensive QOL substudy, patients with more frequent baseline angina reported greater improvements in the symptom, physical functioning, and psychological well-being dimensions of QOL when treated with an invasive strategy, whereas patients who had rare/absent angina at baseline reported no consistent treatment-related QOL differences. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT01471522.


Assuntos
Doença das Coronárias , Qualidade de Vida , Idoso , Angina Pectoris/terapia , Doença Crônica , Tratamento Conservador , Feminino , Humanos , Isquemia , Masculino
17.
Circulation ; 146(17): 1268-1280, 2022 10 25.
Artigo em Inglês | MEDLINE | ID: mdl-35862109

RESUMO

BACKGROUND: Clinical and anatomical characteristics are often considered key factors in deciding between percutaneous coronary intervention (PCI) or coronary artery bypass grafting (CABG) in patients with complex coronary artery disease (CAD) such as left-main CAD or 3-vessel disease. However, little is known about the interaction between self-reported preprocedural physical/mental health and clinical outcomes after revascularization. METHODS: This subgroup analysis of the SYNTAXES trial (SYNTAX Extended Survival), which is the extended follow-up of the randomized SYNTAX trial (Synergy Between PCI With Taxus and Cardiac Surgery) comparing PCI with CABG in patients with left-main CAD or 3-vessel disease, stratified patients by terciles of Physical (PCS) or Mental Component Summary (MCS) scores derived from the preprocedural 36-Item Short Form Health Survey, with higher PCS and MCS scores representing better physical and mental health, respectively. The primary end point was all-cause death at 10 years. RESULTS: A total of 1656 patients with preprocedural 36-Item Short Form Health Survey data were included in the present study. Both higher PCS and MCS were independently associated with lower 10-year mortality (10-point increase in PCS adjusted hazard ratio, 0.84 [95% CI, 0.73-0.97]; P=0.021; in MCS adjusted hazard ratio, 0.85 [95% CI, 0.76-0.95]; P=0.005). A significant survival benefit with CABG over PCI was observed in the highest PCS (>45.5) and MCS (>52.3) terciles with significant treatment-by-subgroup interactions (PCS Pinteraction=0.033, MCS Pinteraction=0.015). In patients with both high PCS (>45.5) and MCS (>52.3), 10-year mortality was significantly higher with PCI compared with CABG (30.5% versus 12.2%; hazard ratio, 2.87 [95% CI, 1.55-5.30]; P=0.001), whereas among those with low PCS (≤45.5) or low MCS (≤52.3), there were no significant differences in 10-year mortality between PCI and CABG, resulting in a significant treatment-by-subgroup interaction (Pinteraction=0.002). CONCLUSIONS: Among patients with left-main CAD or 3-vessel disease, patient-reported preprocedural physical and mental health status was strongly associated with long-term mortality and modified the relative treatment effects of PCI versus CABG. Patients with the best physical and mental health had better 10-year survival with CABG compared with PCI. Assessment of self-reported physical and mental health is important when selecting the optimal revascularization strategy. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; SYNTAXES Unique identifier: NCT03417050. URL: https://www. CLINICALTRIALS: gov; SYNTAX Unique identifier: NCT00114972.


Assuntos
Doença da Artéria Coronariana , Stents Farmacológicos , Intervenção Coronária Percutânea , Humanos , Doença da Artéria Coronariana/cirurgia , Saúde Mental , Medidas de Resultados Relatados pelo Paciente , Fatores de Risco , Resultado do Tratamento , Ensaios Clínicos Controlados Aleatórios como Assunto
18.
N Engl J Med ; 382(17): 1619-1628, 2020 04 23.
Artigo em Inglês | MEDLINE | ID: mdl-32227754

RESUMO

BACKGROUND: In the ISCHEMIA-CKD trial, the primary analysis showed no significant difference in the risk of death or myocardial infarction with initial angiography and revascularization plus guideline-based medical therapy (invasive strategy) as compared with guideline-based medical therapy alone (conservative strategy) in participants with stable ischemic heart disease, moderate or severe ischemia, and advanced chronic kidney disease (an estimated glomerular filtration rate of <30 ml per minute per 1.73 m2 or receipt of dialysis). A secondary objective of the trial was to assess angina-related health status. METHODS: We assessed health status with the Seattle Angina Questionnaire (SAQ) before randomization and at 1.5, 3, and 6 months and every 6 months thereafter. The primary outcome of this analysis was the SAQ Summary score (ranging from 0 to 100, with higher scores indicating less frequent angina and better function and quality of life). Mixed-effects cumulative probability models within a Bayesian framework were used to estimate the treatment effect with the invasive strategy. RESULTS: Health status was assessed in 705 of 777 participants. Nearly half the participants (49%) had had no angina during the month before randomization. At 3 months, the estimated mean difference between the invasive-strategy group and the conservative-strategy group in the SAQ Summary score was 2.1 points (95% credible interval, -0.4 to 4.6), a result that favored the invasive strategy. The mean difference in score at 3 months was largest among participants with daily or weekly angina at baseline (10.1 points; 95% credible interval, 0.0 to 19.9), smaller among those with monthly angina at baseline (2.2 points; 95% credible interval, -2.0 to 6.2), and nearly absent among those without angina at baseline (0.6 points; 95% credible interval, -1.9 to 3.3). By 6 months, the between-group difference in the overall trial population was attenuated (0.5 points; 95% credible interval, -2.2 to 3.4). CONCLUSIONS: Participants with stable ischemic heart disease, moderate or severe ischemia, and advanced chronic kidney disease did not have substantial or sustained benefits with regard to angina-related health status with an initially invasive strategy as compared with a conservative strategy. (Funded by the National Heart, Lung, and Blood Institute; ISCHEMIA-CKD ClinicalTrials.gov number, NCT01985360.).


Assuntos
Angiografia Coronária , Ponte de Artéria Coronária , Nível de Saúde , Isquemia Miocárdica/tratamento farmacológico , Isquemia Miocárdica/cirurgia , Intervenção Coronária Percutânea , Insuficiência Renal Crônica/complicações , Idoso , Teste de Esforço , Feminino , Seguimentos , Estilo de Vida Saudável , Humanos , Análise de Intenção de Tratamento , Masculino , Pessoa de Meia-Idade , Isquemia Miocárdica/complicações , Isquemia Miocárdica/mortalidade , Razão de Chances , Modelos de Riscos Proporcionais , Inquéritos e Questionários
19.
N Engl J Med ; 382(15): 1408-1419, 2020 04 09.
Artigo em Inglês | MEDLINE | ID: mdl-32227753

RESUMO

BACKGROUND: In the ISCHEMIA trial, an invasive strategy with angiographic assessment and revascularization did not reduce clinical events among patients with stable ischemic heart disease and moderate or severe ischemia. A secondary objective of the trial was to assess angina-related health status among these patients. METHODS: We assessed angina-related symptoms, function, and quality of life with the Seattle Angina Questionnaire (SAQ) at randomization, at months 1.5, 3, and 6, and every 6 months thereafter in participants who had been randomly assigned to an invasive treatment strategy (2295 participants) or a conservative strategy (2322). Mixed-effects cumulative probability models within a Bayesian framework were used to estimate differences between the treatment groups. The primary outcome of this health-status analysis was the SAQ summary score (scores range from 0 to 100, with higher scores indicating better health status). All analyses were performed in the overall population and according to baseline angina frequency. RESULTS: At baseline, 35% of patients reported having no angina in the previous month. SAQ summary scores increased in both treatment groups, with increases at 3, 12, and 36 months that were 4.1 points (95% credible interval, 3.2 to 5.0), 4.2 points (95% credible interval, 3.3 to 5.1), and 2.9 points (95% credible interval, 2.2 to 3.7) higher with the invasive strategy than with the conservative strategy. Differences were larger among participants who had more frequent angina at baseline (8.5 vs. 0.1 points at 3 months and 5.3 vs. 1.2 points at 36 months among participants with daily or weekly angina as compared with no angina). CONCLUSIONS: In the overall trial population with moderate or severe ischemia, which included 35% of participants without angina at baseline, patients randomly assigned to the invasive strategy had greater improvement in angina-related health status than those assigned to the conservative strategy. The modest mean differences favoring the invasive strategy in the overall group reflected minimal differences among asymptomatic patients and larger differences among patients who had had angina at baseline. (Funded by the National Heart, Lung, and Blood Institute and others; ISCHEMIA ClinicalTrials.gov number, NCT01471522.).


Assuntos
Angina Pectoris/epidemiologia , Isquemia Miocárdica/terapia , Revascularização Miocárdica/métodos , Qualidade de Vida , Idoso , Angiografia Coronária , Ponte de Artéria Coronária , Doença das Coronárias/diagnóstico por imagem , Doença das Coronárias/tratamento farmacológico , Doença das Coronárias/cirurgia , Feminino , Nível de Saúde , Humanos , Masculino , Pessoa de Meia-Idade , Índice de Gravidade de Doença , Inquéritos e Questionários , Resultado do Tratamento
20.
N Engl J Med ; 382(17): 1608-1618, 2020 04 23.
Artigo em Inglês | MEDLINE | ID: mdl-32227756

RESUMO

BACKGROUND: Clinical trials that have assessed the effect of revascularization in patients with stable coronary disease have routinely excluded those with advanced chronic kidney disease. METHODS: We randomly assigned 777 patients with advanced kidney disease and moderate or severe ischemia on stress testing to be treated with an initial invasive strategy consisting of coronary angiography and revascularization (if appropriate) added to medical therapy or an initial conservative strategy consisting of medical therapy alone and angiography reserved for those in whom medical therapy had failed. The primary outcome was a composite of death or nonfatal myocardial infarction. A key secondary outcome was a composite of death, nonfatal myocardial infarction, or hospitalization for unstable angina, heart failure, or resuscitated cardiac arrest. RESULTS: At a median follow-up of 2.2 years, a primary outcome event had occurred in 123 patients in the invasive-strategy group and in 129 patients in the conservative-strategy group (estimated 3-year event rate, 36.4% vs. 36.7%; adjusted hazard ratio, 1.01; 95% confidence interval [CI], 0.79 to 1.29; P = 0.95). Results for the key secondary outcome were similar (38.5% vs. 39.7%; hazard ratio, 1.01; 95% CI, 0.79 to 1.29). The invasive strategy was associated with a higher incidence of stroke than the conservative strategy (hazard ratio, 3.76; 95% CI, 1.52 to 9.32; P = 0.004) and with a higher incidence of death or initiation of dialysis (hazard ratio, 1.48; 95% CI, 1.04 to 2.11; P = 0.03). CONCLUSIONS: Among patients with stable coronary disease, advanced chronic kidney disease, and moderate or severe ischemia, we did not find evidence that an initial invasive strategy, as compared with an initial conservative strategy, reduced the risk of death or nonfatal myocardial infarction. (Funded by the National Heart, Lung, and Blood Institute and others; ISCHEMIA-CKD ClinicalTrials.gov number, NCT01985360.).


Assuntos
Angiografia Coronária , Ponte de Artéria Coronária , Isquemia Miocárdica/tratamento farmacológico , Isquemia Miocárdica/cirurgia , Intervenção Coronária Percutânea , Insuficiência Renal Crônica/complicações , Antagonistas Adrenérgicos beta/uso terapêutico , Idoso , Bloqueadores dos Canais de Cálcio/uso terapêutico , Teste de Esforço , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/prevenção & controle , Isquemia Miocárdica/complicações , Isquemia Miocárdica/mortalidade , Fatores de Risco
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