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1.
JAMA Netw Open ; 5(5): e2211946, 2022 May 02.
Artigo em Inglês | MEDLINE | ID: mdl-35552723

RESUMO

Importance: Little is known about the long-term outcomes of mild valvular lesions. Objective: To examine the associations of 3 major types of valvular lesions (aortic stenosis, trace or mild aortic regurgitation, and trace or mild mitral regurgitation) with risk of cardiovascular mortality, coronary heart disease (CHD), stroke, heart failure, and atrial fibrillation. Design, Setting, and Participants: This cohort study analyzed data from the ongoing Atherosclerosis Risk in Communities study and focused on Black participants in the Jackson, Mississippi, site who underwent echocardiography at visit 3 from 1993 to 1995. Data analysis was conducted between April 2021 and February 2022. Exposures: Three valvular lesions were analyzed: aortic sclerosis, aortic regurgitation (trace or mild), and mitral regurgitation (trace or mild). Main Outcomes and Measures: The outcomes were cardiovascular mortality, coronary heart disease, heart failure, stroke, and atrial fibrillation. Multivariable Cox proportional hazards regression models were used to examine the independent associations between the 3 valvular lesions and these outcomes. Results: A total of 2106 Black participants were included, with a mean (SD) age of 59.1 (5.6) years and 1354 women (64.3%). The baseline prevalence was 7.7% for aortic sclerosis, 15.1% for aortic regurgitation (6.1% with trace, and 9.0% with mild), and 43.0% for mitral regurgitation (29.4% with trace, and 13.6% with mild). During a median (interquartile interval) follow-up of 22.5 (15.6-23.5) years, 890 participants developed at least 1 cardiovascular outcome. Each valvular lesion was significantly associated with at least 1 cardiovascular outcome: aortic sclerosis was associated with cardiovascular mortality (adjusted hazard ratio [HR], 1.54; 95% CI, 1.06-2.22), mild mitral regurgitation was associated with atrial fibrillation (HR, 1.47; 95% CI, 1.09-1.99), and trace or mild aortic regurgitation was associated with all outcomes (HRs ranging from 1.45 [95% CI, 1.17-1.81] to 1.75 [95% CI, 1.29-2.37]) except stroke. The total number of valvular lesions had graded associations with all cardiovascular outcomes except stroke: the HR of cardiovascular mortality was 1.77 (95% CI, 1.18-2.65) for those with 2 to 3 lesions and was 1.44 (95% CI, 1.05-1.96) for those with 1 lesion vs no lesions. Conclusions and Relevance: Results of this study indicate an association between valvular lesions, even at mild stage, and a long-term risk of cardiovascular events, suggesting the importance of recognizing and monitoring these valvular conditions.

2.
J Am Heart Assoc ; 11(9): e024292, 2022 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-35491988

RESUMO

Background Age-related left atrial (LA) structural and functional abnormalities may be related to subclinical cerebral infarcts (SCIs) and stroke. We evaluated the association of 3-dimensional echocardiographic LA contractility parameters with SCIs and stroke across the spectrum of tertiles of age increment in elderly patients with sinus rhythm, normal ejection fraction, and no history of atrial fibrillation. Methods and Results We enrolled 407 participants (mean age, 76±8 years; 40% men) from ARIC-NCS (Atherosclerosis Risk in Communities Neurocognitive Study) undergoing a brain magnetic resonance imaging and 3-dimensional echocardiographic examinations in 2011 to 2013. The sample was analyzed among age tertiles and subgroups: no cerebral magnetic resonance imaging-detectable infarcts (n=315), magnetic resonance imaging-diagnosed SCIs (n=58), and clinically diagnosed stroke (n=34). The frequency of SCIs significantly increased over age tertiles (P trend 0.023). LA global longitudinal strain-a 3-dimensional echocardiographic index of LA reservoir function-and E/e' divided by LA global longitudinal strain-an index of LA stiffness-worsened across age tertiles (P trend 0.014 and 0.001, respectively), and only in the categories of SCIs (P trend <0.001 and 0.045, respectively) and stroke (P trend 0.001 and 0.011, respectively). LA global longitudinal strain was negatively associated with increased odds of SCIs (P=0.036, P=0.008, and P=0.001, respectively) and strokes (P=0.043, P=0.015, and P=0.001, respectively) over age tertiles, with a significant interaction between age tertiles (interaction P=0.043 and P=0.010, respectively). E/e' divided by LA global longitudinal strain was positively associated with the presence of SCIs (P=0.037, P=0.007, and P=0.001, respectively) and strokes (P=0.045, P=0.007, and P=0.003, respectively) over age tertiles, with a significant interaction only for SCIs (interaction P=0.040) and not for clinical stroke. Conclusions In a large cohort study of elderly patients, among participants with sinus rhythm, normal ejection fraction, and no history of atrial fibrillation, measures of worse age-related LA reservoir function and stiffness are associated with higher odds of SCIs and stroke.


Assuntos
Apêndice Atrial , Fibrilação Atrial , Remodelamento Atrial , Acidente Vascular Cerebral , Idoso , Idoso de 80 Anos ou mais , Fibrilação Atrial/diagnóstico por imagem , Infarto Cerebral , Estudos de Coortes , Feminino , Humanos , Masculino , Acidente Vascular Cerebral/diagnóstico por imagem
3.
Eur J Heart Fail ; 2022 May 12.
Artigo em Inglês | MEDLINE | ID: mdl-35560696

RESUMO

AIMS: N-terminal pro-B-type natriuretic peptide (NT-proBNP), cardiac troponin T (cTnT) and soluble ST2 (sST2) provide complementary prognostic information in HF with reduced ejection fraction (HFrEF). We aimed to assess the association between changes in these markers with changes in cardiac structure, function and health status. METHODS AND RESULTS: Patients in the EVALUATE-HF trial (N=464) were randomized to sacubitril/valsartan or enalapril for 12 weeks, followed by 12-week open-label sacubitril/valsartan. Cardiac biomarkers, echocardiography, and Kansas City Cardiomyopathy Questionnaires (KCCQ) were completed at baseline, and after 12 and 24 weeks. A total of 410 patients (88%) had serial biomarker measurements available (mean age 67±9 years, 75% male and 75% white). After 24 weeks of treatment NT-proBNP, sST2 and cTnT decreased by median (Q1,Q3) -31% (-55%,+6%), -6% (-19%,+8%) and -3% (-13%,+8%), respectively (all P<0.001). Decreases in NT-proBNP were associated with reductions in cardiac volumes and improvements in systolic and diastolic function and health status. Decreases in cTnT were associated with reductions in LV mass, but not with changes in LV function or KCCQ. Decreases in sST2 were consistently associated with improvements in health status, but not with measures of cardiac structure or function. There were no effect modification from treatment on the associations investigated (P-for-interaction>0.05). CONCLUSION: In HFrEF, serial changes in NT-proBNP correlate with changes in several key measures of cardiac structure and health status. cTnT changes correlate with changes in LV mass and sST2 with changes in health status. These data highlight possible complementary pathophysiologic implications of changes NT-proBNP, cTnT and sST2.

4.
Chest ; 2022 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-35562059

RESUMO

BACKGROUND: Atrial fibrillation (AF) is widely perceived to originate from the left atrium (LA). It is unclear whether increases in right ventricular (RV) afterload in older adults plays an etiological role in AF genesis independent of LA and left ventricular (LV) remodeling. RESEARCH QUESTION: Is higher RV afterload associated with greater AF risk independent of LA and LV remodeling? STUDY DESIGN AND METHODS: In this observational prospective study, we included 2246 community-dwelling older adults (mean age, 75 years) without known cardiovascular disease, with LV ejection fraction >50%, LA volume index <34 ml/m2, and E/e' ratio <14 and a measurable functional tricuspid regurgitation jet velocity. From 2D-echocardiograms, we estimated pulmonary artery systolic pressure (PASP) and pulmonary vascular resistance (PVR). We ascertained incident AF (through 2018) from hospital discharge codes and death certificates. We estimated hazard ratios (HR) by Cox regression. RESULTS: During follow-up (median 6.3 years, interquartile interval 5.5-6.9 years), 215 participants developed AF. AF risk was significantly higher in the third (vs first) tertile of PASP [HR 1.65, 95% confidence interval (CI) 1.08 - 2.54] and PVR [HR 1.38, 95% CI 1.00 - 2.08] independent of LA and LV structure and function, heart rate, body mass index, prevalent sleep apnea, systemic blood pressure, antihypertensive medications, lung, kidney, and thyroid function. These associations persisted after further exclusion of participants with tricuspid regurgitation jet velocity >2.8 m/s and lateral and septal mitral annular velocity above age- and sex-specific reference limits. INTERPRETATION: In older adults, higher RV afterload is associated with greater AF risk independent of LA and LV remodeling. Future research should focus on confirming this novel association and elucidate underlying mechanisms.

5.
J Am Coll Cardiol ; 79(16): 1549-1561, 2022 04 26.
Artigo em Inglês | MEDLINE | ID: mdl-35450571

RESUMO

BACKGROUND: Limited data exist to characterize novel measures of left atrial (LA) structure and function in older adults without prevalent heart failure (HF). OBJECTIVES: The aim was to assess reference range of LA measures, their associations with N-terminal pro-B-type natriuretic-peptide (NT-proBNP) and the related risk for incident HF or death. METHODS: We analyzed LA structure (LA maximal [LAViMax] and minimal volume indexed by body surface area) and function (LA emptying fraction, LA reservoir, conduit, and contraction strain) in 4,901 participants from the ARIC (Atherosclerosis Risk In Communities) study (mean age 75 ± 5 years, 40% male, and 19% Black) without prevalent HF. We assessed sex-specific 10th and 90th percentile ARIC-based reference limits in 301 participants free of prevalent cardiovascular disease, and related LA measures to NT-proBNP and incident HF or death (median follow-up of 5.5 years) in the whole ARIC cohort. RESULTS: Approximately 20% of the overall population had LA abnormalities according to the ARIC-based reference limit. Each LA measure was associated with NT-proBNP and, except for LAViMax, with incident HF or death after multivariable adjustment (including left ventricular function and NT-proBNP). Results were consistent in participants with normal LAViMax (P for interaction > 0.05). LA measures were prognostic for both incident HF with preserved ejection fraction or death and incident HF with reduced ejection fraction or death. When added to HF risk factors and NT-proBNP (baseline C-statistics = 0.74) all LA measures, except for LAViMax, significantly enhanced the prognostic accuracy. CONCLUSIONS: Novel measures of LA structure and function, but not standard assessment by LAViMax, are associated with increased risk of incident HF or death regardless of measures of left ventricular function and NT-proBNP.


Assuntos
Cardiopatias , Insuficiência Cardíaca , Idoso , Idoso de 80 Anos ou mais , Biomarcadores , Feminino , Átrios do Coração/diagnóstico por imagem , Insuficiência Cardíaca/diagnóstico , Insuficiência Cardíaca/epidemiologia , Humanos , Masculino , Peptídeo Natriurético Encefálico , Fragmentos de Peptídeos , Volume Sistólico , Função Ventricular Esquerda
6.
JACC Heart Fail ; 10(5): 306-318, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35483792

RESUMO

OBJECTIVES: This study aimed to assess the prognostic importance of hyponatremia and the effects of dapagliflozin on serum sodium in the DAPA-HF (Dapagliflozin And Prevention of Adverse outcomes in Heart Failure) trial. BACKGROUND: Hyponatremia is common and prognostically important in hospitalized patients with heart failure with reduced ejection fraction, but its prevalence and importance in ambulatory patients are uncertain. METHODS: We calculated the incidence of the primary outcome (cardiovascular death or worsening heart failure) and secondary outcomes according to sodium category (≤135 and >135 mmol/L). Additionally, we assessed: 1) whether baseline serum sodium modified the treatment effect of dapagliflozin; and 2) the effect of dapagliflozin on serum sodium. RESULTS: Of 4,740 participants with a baseline measurement, 398 (8.4%) had sodium ≤135 mmol/L. Participants with hyponatremia were more likely to have diabetes, be treated with diuretics, and have lower systolic blood pressure, left ventricular ejection fraction, and estimated glomerular filtration rate. Hyponatremia was associated with worse outcomes even after adjustment for predictive variables (adjusted HRs for the primary outcome 1.50 [95% CI: 1.23-1.84] and all-cause death 1.59 [95% CI: 1.26-2.01]). The benefits of dapagliflozin were similar in patients with and without hyponatremia (HR for primary endpoint: 0.83 [95% CI: 0.57-1.19] and 0.73 [95% CI: 0.63-0.84], respectively, P for interaction = 0.54; HR for all-cause death: 0.85 [95% CI: 0.56-1.29] and 0.83 [95% CI: 0.70-0.98], respectively, P for interaction = 0.96). Between baseline and day 14, more patients on dapagliflozin developed hyponatremia (11.3% vs 9.4%; P = 0.04); thereafter, this pattern reversed and at 12 months fewer patients on dapagliflozin had hyponatremia (4.6% vs 6.7%; P = 0.003). CONCLUSIONS: Baseline serum sodium concentration was prognostically important, but did not modify the benefits of dapagliflozin on morbidity and mortality in heart failure with reduced ejection fraction. (Study to Evaluate the Effect of Dapagliflozin on the Incidence of Worsening Heart Failure or Cardiovascular Death in Patients With Chronic Heart Failure [DAPA-HF]: NCT03036124).


Assuntos
Insuficiência Cardíaca , Hiponatremia , Disfunção Ventricular Esquerda , Compostos Benzidrílicos , Glucosídeos , Humanos , Hiponatremia/complicações , Hiponatremia/epidemiologia , Sódio , Volume Sistólico , Disfunção Ventricular Esquerda/complicações , Função Ventricular Esquerda
7.
JACC Heart Fail ; 10(5): 336-346, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35483796

RESUMO

OBJECTIVES: In this study, the authors sought to assess the relationship between AFF and outcomes, the treatment response to sacubitril/valsartan and first-detected AFF in patients with HFpEF enrolled in the PARAGON-HF trial. BACKGROUND: Atrial fibrillation and flutter (AFF) are common in heart failure with preserved ejection fraction (HFpEF) and increase the risk of adverse outcomes. METHODS: A total of 4,776 patients formed 3 groups: those with AFF according to electrocardiography (ECG) at enrollment (n = 1,552; 33%), those with history of AFF but without AFF on ECG at enrollment (n = 1,005; 21%), and those without history of AFF or AFF on ECG at enrollment (n = 2,219, 46%). We assessed outcomes, treatment response to sacubitril/valsartan in each group, and the risk associated with first-detected AFF in patients without any known AFF. The primary outcome was a composite of total heart failure hospitalizations and cardiovascular death. RESULTS: History of AFF and AFF at enrollment were associated with higher risk of the primary outcome (risk ratio [RR]: 1.36 [95% CI: 1.12-1.65] and RR: 1.31 [1.11-1.54], respectively), than no AFF. Neither history of AFF nor AFF at enrollment modified the treatment effect of sacubitril/valsartan. Post randomization AFF occurred in 12% of patients without previous AFF and was associated with 2.8-fold higher risk of the primary outcome, but it was not influenced by sacubitril/valsartan. CONCLUSIONS: History of AFF and AFF on ECG at enrollment were associated with a higher risk of the primary outcome. First-detected AFF was not influenced by sacubitril/valsartan, yet it was associated with increased risk of all subsequent outcomes and may represent a potential target for future HFpEF trials. (Efficacy and Safety of LCZ696 Compared to Valsartan, on Morbidity and Mortality in Heart Failure Patients With Preserved Ejection Fraction [PARAGON-HF]; NCT01920711).


Assuntos
Fibrilação Atrial , Insuficiência Cardíaca , Aminobutiratos , Antagonistas de Receptores de Angiotensina/uso terapêutico , Fibrilação Atrial/complicações , Fibrilação Atrial/tratamento farmacológico , Compostos de Bifenilo , Humanos , Volume Sistólico/fisiologia , Tetrazóis/uso terapêutico , Valsartana/efeitos adversos
8.
Ann Intern Med ; 2022 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-35467935

RESUMO

BACKGROUND: Frailty may modify the risk-benefit profile of certain treatments, and frail patients may have reduced tolerance to treatments. OBJECTIVE: To investigate the efficacy of dapagliflozin according to frailty status, using the Rockwood cumulative deficit approach, in DAPA-HF (Dapagliflozin and Prevention of Adverse Outcomes in Heart Failure). DESIGN: Post hoc analysis of a phase 3 randomized clinical trial. (ClinicalTrials.gov: NCT03036124). SETTING: 410 sites in 20 countries. PATIENTS: Patients with symptomatic heart failure (HF) with a left ventricular ejection fraction of 40% or less and elevated natriuretic peptide. INTERVENTION: Addition of once-daily 10 mg of dapagliflozin or placebo to guideline-recommended therapy. MEASUREMENTS: The primary outcome was worsening HF or cardiovascular death. RESULTS: Of the 4744 patients randomly assigned in DAPA-HF, a frailty index (FI) was calculable in 4742. In total, 2392 patients (50.4%) were in FI class 1 (FI ≤0.210; not frail), 1606 (33.9%) in FI class 2 (FI 0.211 to 0.310; more frail), and 744 (15.7%) in FI class 3 (FI ≥0.311; most frail). The median follow-up time was 18.2 months. Dapagliflozin reduced the risk for worsening HF or cardiovascular death, regardless of FI class. The differences in event rate per 100 person-years for dapagliflozin versus placebo from lowest to highest FI class were -3.5 (95% CI, -5.7 to -1.2), -3.6 (CI, -6.6 to -0.5), and -7.9 (CI, -13.9 to -1.9). Consistent benefits were observed for other clinical events and health status, but the absolute reductions were generally larger in the most frail patients. Study drug discontinuation and serious adverse events were not more frequent with dapagliflozin than placebo, regardless of FI class. LIMITATION: Enrollment criteria precluded the inclusion of very high-risk patients. CONCLUSION: Dapagliflozin improved all outcomes examined, regardless of frailty status. However, the absolute reductions were larger in more frail patients. PRIMARY FUNDING SOURCE: AstraZeneca.

9.
JAMA Netw Open ; 5(4): e228873, 2022 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-35486404

RESUMO

Importance: Influenza infection is associated with increased cardiovascular hospitalization and mortality. Our prior systematic review and meta-analysis hypothesized that influenza vaccination was associated with a lower risk of cardiovascular events. Objective: To evaluate, via an updated meta-analysis, if seasonal influenza vaccination is associated with a lower risk of fatal and nonfatal cardiovascular events and assess whether the newest cardiovascular outcome trial results are consistent with prior findings. Data Sources: A previously published meta-analysis of randomized controlled trials (RCTs) and a large 2021 cardiovascular outcome trial. Study Selection: Studies with RCTs published between 2000 and 2021 that randomized participants to either influenza vaccine or placebo/control. Eligible participants were inpatients and outpatients recruited for international multicenter RCTs and randomized to receive either influenza vaccine or placebo/control. Data Extraction and Synthesis: PRISMA guidelines were followed in the extraction of study details, and risk of bias was assessed using the Cochrane Collaboration tool. Trial quality was evaluated using Cochrane criteria. Data were analyzed January 2020 and December 2021. Main Outcomes and Measures: Random-effects Mantel-Haenszel risk ratios (RRs) and 95% CIs were derived for a composite of major adverse cardiovascular events and cardiovascular mortality within 12 months of follow-up. Where available, analyses were stratified by patients with and without recent acute coronary syndrome (ACS) within 1 year of randomization. Results: Six published RCTs comprising a total of 9001 patients were included (mean age, 65.5 years; 42.5% women; 52.3% with a cardiac history). Overall, influenza vaccine was associated with a lower risk of composite cardiovascular events (3.6% vs 5.4%; RR, 0.66; 95% CI, 0.53-0.83; P < .001). A treatment interaction was detected between patients with recent ACS (RR, 0.55; 95% CI, 0.41-0.75) and without recent ACS (RR, 1.00; 95% CI, 0.68-1.47) (P for interaction = .02). For cardiovascular mortality, a treatment interaction was also detected between patients with recent ACS (RR, 0.44; 95% CI, 0.23-0.85) and without recent ACS (RR, 1.45; 95% CI, 0.84-2.50) (P for interaction = .006), while 1.7% of vaccine recipients died of cardiovascular causes compared with 2.5% of placebo or control recipients (RR, 0.74; 95% CI, 0.42-1.30; P = .29). Conclusions and Relevance: In this study, receipt of influenza vaccination was associated with a 34% lower risk of major adverse cardiovascular events, and individuals with recent ACS had a 45% lower risk. Given influenza poses a threat to population health during the COVID-19 pandemic, it is integral to counsel high-risk patients on the cardiovascular benefits of influenza vaccination.


Assuntos
Síndrome Coronariana Aguda , COVID-19 , Vacinas contra Influenza , Influenza Humana , Síndrome Coronariana Aguda/tratamento farmacológico , Idoso , Feminino , Fatores de Risco de Doenças Cardíacas , Humanos , Vacinas contra Influenza/uso terapêutico , Influenza Humana/tratamento farmacológico , Influenza Humana/prevenção & controle , Masculino , Estudos Multicêntricos como Assunto , Ensaios Clínicos Controlados Aleatórios como Assunto , Vacinação
10.
Circulation ; 2022 Apr 20.
Artigo em Inglês | MEDLINE | ID: mdl-35442064

RESUMO

Background: In a post hoc analysis, the frequency of occurrence of an early decline ("dip") in estimated glomerular filtration rate (eGFR) after initiation of dapagliflozin, and its association with outcomes, was evaluated in patients with heart failure and reduced ejection fraction (HFrEF) randomized in the Dapagliflozin and Prevention of Adverse outcomes in Heart Failure trial. Methods: HFrEF patients with or without type 2 diabetes and an eGFR ≥30 mL/min/1.73m2 were randomized to placebo or dapagliflozin 10mg daily. The primary outcome was the composite of worsening heart failure or cardiovascular death. The extent of the dip in eGFR between baseline and 2 weeks, patient characteristics associated with a >10% decline, and cardiovascular outcomes and eGFR slopes in participants experiencing this decline were investigated. Time-to-event outcomes were assessed in Cox regression from 14 days; eGFR slopes were assessed using repeated measure mixed effect models. Results: The mean change in eGFR between day 0 and 14 was -1.1 ml/min/1.73m2 (95% CI -1.5,-0.7) with placebo and -4.2 ml/min/1.73m2 (-4.6,-3.9) with dapagliflozin, giving a between treatment difference of 3.1 (2.6, 3.7) ml/min/1.73m2. The proportions of patients randomized to dapagliflozin experiencing a >10%, >20% and >30% decline in eGFR were: 38.2%, 12.6%, and 3.4%, respectively; for placebo they were 21.0%, 6.4% and 1.3%, respectively. The odds ratio for a >10% early decline in eGFR with dapagliflozin, compared with placebo, was 2.36 (95%CI 2.07-2.69), P<0.001. Baseline characteristics associated with a >10% decline in eGFR on dapagliflozin were older age, lower eGFR, higher ejection fraction, and type 2 diabetes. The hazard ratio for the primary outcome in patients in the placebo group experiencing a >10% decline in eGFR, compared with ≤10% decline in eGFR was 1.45 (95% CI 1.19-1.78). The corresponding hazard ratio in the dapagliflozin group was 0.73 (95% CI 0.59-0.91), P-interaction <0.001. A >10% initial decline in eGFR was not associated with greater long-term decline in eGFR or more adverse events. Conclusions: The average dip in eGFR after starting dapagliflozin was small and associated with better clinical outcomes, compared with a similar decline on placebo in patients with HFrEF. Large declines in eGFR were uncommon with dapagliflozin.

11.
Pilot Feasibility Stud ; 8(1): 87, 2022 Apr 21.
Artigo em Inglês | MEDLINE | ID: mdl-35449028

RESUMO

BACKGROUND: High-dose influenza vaccines provide better protection against influenza infection than standard-dose in persons aged 65 years and above; however, in most countries, high-dose vaccines are not widely implemented. Assessing the relative effectiveness of high-dose compared to standard-dose vaccines on hospitalizations and mortality would enable more robust public health and cost-effectiveness estimates. This study aims to investigate the feasibility of conducting a pragmatic randomized clinical trial in Denmark comparing high-dose to standard-dose vaccines utilizing existing vaccination infrastructure and the Danish nationwide health registries for data collection. METHODS: The DANFLU-1 trial (NCT05048589) is a pragmatic, open-label, active-controlled randomized trial randomizing Danish citizens aged 65-79 years to either high-dose quadrivalent influenza vaccine or standard-dose quadrivalent influenza vaccine. The study utilizes the infrastructure of a private vaccination provider (Danske Lægers Vaccinations Service) for recruitment, inclusion, randomization, and vaccination. All collection of baseline and follow-up data including safety monitoring is performed centrally by the Department of Cardiology at Herlev and Gentofte Hospital, Copenhagen, Denmark using the Danish nationwide health registries. The study aims to include 40,000 participants during the 2021/2022 influenza season. The primary endpoints address feasibility and include the number of participants enrolled, randomization balance, and representativeness compared to the Danish general population. Relative vaccine effectiveness will also be assessed, however, this feasibility study is not powered for clinical outcomes and may be affected by the COVID-19 pandemic. DISCUSSION: The DANFLU-1 study is investigating the feasibility of conducting a large-scale pragmatic clinical trial in Denmark utilizing existing infrastructure and the Danish nationwide registries. This will provide valuable insight, especially for potential future fully powered vaccine trials, but also for trials wishing to investigate other interventions. TRIAL REGISTRATION: Clinicaltrials.gov : NCT05048589 , registered September 17, 2021.

12.
JAMA Cardiol ; 2022 Apr 27.
Artigo em Inglês | MEDLINE | ID: mdl-35476049

RESUMO

Importance: Sex- and race-based differences in N-terminal pro-B-type natriuretic peptide (NT-proBNP) concentrations are poorly understood. Clinical decisions are often informed by absolute-as opposed to relative-risk, but absolute risk of incident heart failure (HF) associated with NT-proBNP concentration across these important demographic categories is unclear. Objective: To determine whether physiologic determinants of NT-proBNP concentrations account for sex and race differences, and to more uniformly predict HF risk using NT-proBNP in these demographic subgroups. Design, Setting, and Participants: In the longitudinal Atherosclerosis Risk in Communities epidemiologic prospective community-based cohort study, the association of NT-proBNP concentration with relative and absolute risk of HF by sex- and race-based categories was assessed at study visit 2 (1990-1992) and study visit 5 (2011-2013) using Cox and Poisson regression. These data were analyzed from June 2018 to October 2021. The contribution of clinical, anthropometric, echocardiographic, and laboratory parameters to sex- and race-based differences in NT-proBNP concentration was assessed at visit 5 using linear regression. Participants included were free of HF in midlife (visit 2; a total of 12 750 participants) and late life (visit 5; a total of 5191 participants). Exposures: NT-proBNP concentration. Main Outcomes and Measures: Incident HF or death. Results: Among the 5191 HF-free participants at visit 5, the mean (SD) age was 76.0 (5.2) years, 2104 (41%) were male, 1043 (20%) were Black, and the median (IQR) NT-proBNP concentration was 124 (64-239) pg/. In both midlife and late life, NT-proBNP concentration was lowest in Black men (median [IQR] concentration: visit 2, 30 [14-67] pg/mL; visit 5, 74 [34-153] pg/mL) and highest in White women (median [IQR] concentration: visit 2, 70 [42-111] pg/mL; visit, 5, 154 [82-268] pg/mL). Sex and race differences in NT-proBNP concentration persisted after accounting for age, income, education, area deprivation index, cardiovascular diseases, left ventricular structure (LV), LV function, LV wall stress, weight and fat mass, and estimated glomerular filtration rate. Substantial differences in the absolute risk of incident HF or death existed across the sex- and race-based categories at any NT-proBNP concentration (eg, 7-fold [rate ratio, 6.7; 95% CI, 4.6-9.9] and 3-fold [rate ratio, 2.7; 95% CI, 1.7-4.1] difference at visit 2 and visit 5, respectively, at guideline-recommended thresholds) with higher risk consistently observed among Black men and lower risk in White women. Results were replicated in a cohort of participants from the Cardiovascular Health Study. Conclusions and Relevance: In this study, sex- and race-based differences in NT-proBNP persisted after accounting for known physiologic determinants. Absolute risk associated with a given value of NT-proBNP varied substantially by sex and race. Consideration of NT-proBNP values in the context of sex and race allows for more uniform prediction of absolute risk across important demographic subgroups.

13.
J Am Heart Assoc ; 11(8): e021327, 2022 Apr 19.
Artigo em Inglês | MEDLINE | ID: mdl-35383463

RESUMO

Background Baseline and temporal changes in natriuretic peptide (NP) concentrations have strong prognostic value with regard to long-term cardiovascular risk stratification. To increase the clinical utility of NP sampling for patient management, we wanted to assess the incremental predictive value of 2 serial NP measurements compared with a single measurement and provide absolute risk estimates for cardiovascular death or heart failure hospitalization (HFH) within 6 months based on 2 serial NP measurements. Methods and Results Consecutive NP samples obtained from 5393 patients with a recent coronary event and type 2 diabetes enrolled in the ELIXA (Evaluation of Cardiovascular Outcomes in Patients With Type 2 Diabetes After Acute Coronary Syndrome During Treatment With Lixisenatide) trial were used to construct best logistic regression models with outcome of cardiovascular death or HFH (136 events). Absolute risk estimates of cardiovascular death or HFH within 6 months using either BNP (B-type natriuretic peptide) or NT-proBNP (N-terminal pro-BNP) serial measurements were depicted based on the concentrations of 2 serial NP measurements. During the 6-month follow-up periods, the incidence rate (±95% CIs) of cardiovascular death or HFH for patients was 14.0 (11.8‒16.6) per 1000 patient-years. Risk prediction depended on NP concentrations from both prior and current sampling. NP sampling 6 months apart improved the predictive value and reclassification of patients compared with a single sample (AUROC [Area Under the Receiver Operating Characteristic curve]: BNP, P=0.003. NT-proBNP, P<0.0001), with a majority of moderate-risk patients (6-month risk between 1% and 10%) being reclassified on the basis of the second NP sample. Conclusions Serial NP measurements improved prediction of imminent cardiovascular death or HFH in patients with coronary artery disease and type 2 diabetes. The absolute risk estimates provided may aid clinicians in decision-making and help patients understand their short-term risk profile.


Assuntos
Doença da Artéria Coronariana , Diabetes Mellitus Tipo 2 , Insuficiência Cardíaca , Biomarcadores , Doença da Artéria Coronariana/complicações , Doença da Artéria Coronariana/diagnóstico , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/epidemiologia , Insuficiência Cardíaca/diagnóstico , Insuficiência Cardíaca/epidemiologia , Hospitalização , Humanos , Peptídeo Natriurético Encefálico , Peptídeos Natriuréticos , Fragmentos de Peptídeos , Valor Preditivo dos Testes , Prognóstico , Vasodilatadores
14.
Circulation ; 2022 Mar 31.
Artigo em Inglês | MEDLINE | ID: mdl-35354306

RESUMO

Background: In the REDUCE LAP-HF II trial, implantation of an atrial shunt device did not provide, overall, clinical benefit for patients with heart failure and preserved or mildly reduced ejection fraction (HFpEF/HFmrEF). However, pre-specified analyses identified differences in response in subgroups defined by pulmonary artery systolic pressure during submaximal exercise, right atrial (RA) volume, and sex. Shunt implantation reduces left atrial (LA) pressures but increases pulmonary blood flow, which may be poorly tolerated in patients with pulmonary vascular disease (PVD). Based upon these results, we hypothesized that patients with latent PVD, defined as elevated pulmonary vascular resistance (PVR) during exercise, might be harmed by shunt implantation, and conversely that patients without PVD might benefit. Methods: REDUCE LAP-HF II enrolled 626 patients with HF, EF ≥40%, exercise pulmonary capillary wedge pressure ≥25 mmHg, and resting PVR <3.5 WU who were randomized 1:1 to atrial shunt device or sham control. The primary outcome, a hierarchical composite of cardiovascular death, nonfatal ischemic stroke, recurrent HF events, and change in health status, was analyzed using the win ratio. Latent PVD was defined as PVR ≥1.74 WU (highest tertile) at peak exercise, measured prior to randomization. Results: Compared to patients without PVD (n=382), those with latent PVD (n=188) were older, had more atrial fibrillation and right heart dysfunction, and were more likely to have elevated LA pressure at rest. Shunt treatment was associated with worse outcomes in patients with PVD (win ratio 0.60, [95% CI 0.42, 0.86]; p=0.005) and signal of clinical benefit in patients without PVD (win ratio 1.31 [95% CI 1.02, 1.68]; p=0.038). Patients with larger RA volumes and men had worse outcomes with the device, and both groups were more likely to have pacemakers, HFmrEF, and increased LA volume. For patients without latent PVD or pacemaker (n=313, 50% of randomized patients), shunt treatment resulted in more robust signal of clinical benefit (win ratio 1.51 [95% CI 1.14, 2.00]; p=0.004). Conclusions: In patients with HFpEF/HFmrEF, the presence of latent PVD uncovered by invasive hemodynamic exercise testing identifies patients who may worsen with atrial shunt therapy, whereas those without latent PVD may benefit.

15.
JACC Heart Fail ; 10(3): 184-197, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-35241246

RESUMO

OBJECTIVES: This report describes the baseline clinical profiles and management of DELIVER (Dapagliflozin Evaluation to Improve the Lives of Patients With Preserved Ejection Fraction Heart Failure) trial participants and how these compare with those in other contemporary heart failure with preserved ejection fraction trials. BACKGROUND: The DELIVER trial was designed to evaluate the effects of the sodium-glucose cotransporter-2 inhibitor dapagliflozin on cardiovascular death, heart failure (HF) hospitalization, or urgent HF visits in patients with HF with mildly reduced and preserved left ventricular ejection fraction (LVEF). METHODS: Adults with symptomatic HF and LVEF >40%, with or without type 2 diabetes mellitus, elevated N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels, and evidence of structural heart disease were randomized to dapagliflozin 10 mg once daily or matching placebo. RESULTS: A total of 6,263 patients were randomized (mean age: 72 ± 10 years; 44% women; 45% type 2 diabetes mellitus; 45% with body mass index ≥30 kg/m2; and 57% with history of atrial fibrillation or flutter). Most participants had New York Heart Association functional class II symptoms (75%). Baseline mean LVEF was 54.2 ± 8.8% and median NT-proBNP of 1,399 pg/mL (IQR: 962 to 2,210 pg/mL) for patients in atrial fibrillation/flutter compared with 716 pg/mL (IQR: 469 to 1,281 pg/mL) in those who were not. Patients in both hospitalized and ambulatory settings were enrolled, including 10% enrolled in-hospital or within 30 days of a hospitalization for HF. Eighteen percent of participants had HF with improved LVEF. CONCLUSIONS: DELIVER is the largest and broadest clinical trial of this population to date and enrolled high-risk, well-treated patients with HF with mildly reduced and preserved LVEF. (Dapagliflozin Evaluation to Improve the Lives of Patients With Preserved Ejection Fraction Heart Failure [NCT03619213]).


Assuntos
Fibrilação Atrial , Diabetes Mellitus Tipo 2 , Insuficiência Cardíaca , Inibidores do Transportador 2 de Sódio-Glicose , Idoso , Idoso de 80 Anos ou mais , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/tratamento farmacológico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Peptídeo Natriurético Encefálico/uso terapêutico , Fragmentos de Peptídeos , Inibidores do Transportador 2 de Sódio-Glicose/farmacologia , Inibidores do Transportador 2 de Sódio-Glicose/uso terapêutico , Volume Sistólico , Função Ventricular Esquerda
16.
JAMA ; 327(12): 1138-1148, 2022 03 22.
Artigo em Inglês | MEDLINE | ID: mdl-35315884

RESUMO

Importance: Atrial myopathy-characterized by alterations in left atrial (LA) function and size-is associated with ischemic stroke, independent of atrial fibrillation (AF). Electrocardiographic markers of atrial myopathy are associated with dementia, but it is unclear whether 2-dimensional echocardiographic (2DE)-defined LA function and size are associated with dementia. Objective: To examine the association of LA function and size with incident dementia. Design, Setting, and Participants: The Atherosclerosis Risk in Communities (ARIC) study is a community-based prospective cohort. An exploratory, retrospective analysis was conducted. ARIC centers are located in Forsyth County, North Carolina; Jackson, Mississippi; Washington County, Maryland; and suburban Minneapolis, Minnesota. For this analysis, visit 5 (2011-2013) served as the baseline. Participants without prevalent AF and stroke and who had 2DEs in 2011-2013 were included and surveilled through December 31, 2019. Exposures: LA function (reservoir strain, conduit strain, contractile strain, emptying fraction, passive emptying fraction, and active emptying fraction), and LA size (maximal and minimal volume index) as evaluated by 2DE. Main Outcomes and Measures: Dementia cases were identified using in-person and phone cognitive assessments, hospitalization codes, and death certificates. Cox proportional hazards models were used. Results: Among 4096 participants (mean [SD] age, 75 [5] years; 60% women; 22% Black individuals), 531 dementia cases were ascertained over a median follow-up of 6 years. Dementia incidence for the lowest LA quintile was 4.80 for reservoir strain, 3.94 for conduit strain, 3.29 for contractile strain, 4.20 for emptying fraction, 3.67 for passive emptying fraction, and 3.27 for active emptying fraction per 100 person-years. After full-model adjustments, there were statistically significant associations between measures of LA function and dementia; the hazard ratios (HRs) from the lowest vs highest quintile for reservoir strain were 1.98 (95% CI, 1.42-2.75); for conduit strain, 1.50 (95% CI, 1.09-2.06); for contractile strain, 1.57 (95% CI, 1.16-2.14); for emptying fraction, 1.87 (95% CI, 1.31-2.65); and for active emptying fraction, 1.43 (95% CI, 1.04-1.96). LA passive emptying fraction was not significantly associated with dementia (HR, 1.26 [95% CI, 0.93-1.71]). Dementia incidence for the highest LA maximal volume index quintile was 3.18 per 100 person-years (HR for highest vs lowest quintile, 0.77 [95% CI, 0.58-1.02]) and for the highest minimal volume index quintile was 3.50 per 100 person-years (HR for the highest vs lowest quintile, 0.95 [95% CI, 0.71-1.28]). Both measures were not significantly associated with dementia. These findings were robust to sensitivity analyses that excluded participants with incident AF or stroke. Conclusions and Relevance: In this exploratory analysis of a US community-based cohort, several echocardiographic measures of lower LA function were significantly associated with an increased risk of subsequent dementia. Measures of LA size were not significantly associated with dementia risk. These findings suggest that impaired LA function may be a risk factor associated with dementia.


Assuntos
Função do Átrio Esquerdo , Demência/diagnóstico por imagem , Demência/fisiopatologia , Ecocardiografia , Átrios do Coração/anatomia & histologia , Átrios do Coração/diagnóstico por imagem , Idoso , Idoso de 80 Anos ou mais , Demência/epidemiologia , Feminino , Humanos , Incidência , Masculino , Tamanho do Órgão , Estudos Retrospectivos
17.
Eur Heart J ; 2022 Mar 23.
Artigo em Inglês | MEDLINE | ID: mdl-35325102

RESUMO

AIMS: In GALACTIC-HF, the cardiac myosin activator omecamtiv mecarbil compared with placebo reduced the risk of heart failure events or cardiovascular death in patients with heart failure with reduced ejection fraction. We explored the influence of atrial fibrillation or flutter (AFF) on the effectiveness of omecamtiv mecarbil. METHODS AND RESULTS: GALACTIC-HF enrolled patients with New York Heart Association (NYHA) Class II-IV heart failure, left ventricular ejection fraction ≤35%, and elevated natriuretic peptides. We assessed whether the presence or absence of AFF, a pre-specified subgroup, modified the treatment effect for the primary and secondary outcomes, and additionally explored effect modification in patients who were or were not receiving digoxin. Patients with AFF (n = 2245, 27%) were older, more likely to be randomized as an inpatient, less likely to have a history of ischaemic aetiology or myocardial infarction, had a worse NYHA class, worse quality of life, lower estimated glomerular filtration rate, and higher N-terminal pro-B-type natriuretic peptide. The treatment effect of omecamtiv mecarbil was modified by baseline AFF (interaction P = 0.012), with patients without AFF at baseline deriving greater benefit. The worsening of the treatment effect by baseline AFF was significantly more pronounced in digoxin users than in non-users (interaction P = 0.007); there was minimal evidence of effect modification in those patients not using digoxin (P = 0.47) or in digoxin users not in AFF. CONCLUSION: Patients in AFF at baseline were less likely to benefit from omecamtiv mecarbil than patients without AFF, although the attenuation of the treatment effect was disproportionally concentrated in patients with AFF who were also receiving digoxin.Clinical Trial Registration: NCT02929329.

18.
J Am Heart Assoc ; 11(6): e022308, 2022 03 15.
Artigo em Inglês | MEDLINE | ID: mdl-35253447

RESUMO

Background Whether cardiac structure and function abnormalities associated with dysglycemia are sufficient to explain the increased risk of death or heart failure (HF) remains unclear. Methods and Results We analyzed 6059 participants (mean age, 75±5 years; 58% women; and 22% Black individuals) who attended the ARIC (Atherosclerosis Risk in Communities) study visit 5 examination (2011-2013). Participants were categorized as no diabetes, pre-diabetes, and diabetes (on the basis of medical history and glycated hemoglobin values). We assessed whether diabetes modified the association between echocardiographic measures of cardiac structure and function and the composite of all-cause death or HF hospitalization and then estimated the extent to which the increased risk of the composite outcome associated with diabetes was explained by cardiac structure and function. Diabetes was prevalent in 33.5% of the subjects. Death or HF occurred in 1111 (18%) at a rate of 3.6 per 100 person-years. Both measures of cardiac structure and function and diabetes status were significantly associated with worse prognosis after accounting for clinical confounders. While diabetes was consistently associated with a higher risk of events, it did not significantly modify the association between cardiac abnormalities and the risk of death or HF, except for subjects with higher left atrial volume who showed higher relative risk of events (P for interaction <0.001). Measures of cardiac structure and function accounted for ≈16% of the increased risk of death or HF associated with diabetes. Similar results were observed analyzing subjects without prevalent heart disease. Conclusions In a biracial cohort of older adults, the increased risk of events associated with diabetes was partially explained by cardiac structure and function abnormalities.


Assuntos
Diabetes Mellitus , Insuficiência Cardíaca , Idoso , Idoso de 80 Anos ou mais , Diabetes Mellitus/epidemiologia , Ecocardiografia/métodos , Feminino , Átrios do Coração , Insuficiência Cardíaca/diagnóstico , Humanos , Masculino , Fatores de Risco , Volume Sistólico , Função Ventricular Esquerda
19.
Lancet ; 399(10330): 1130-1140, 2022 03 19.
Artigo em Inglês | MEDLINE | ID: mdl-35120593

RESUMO

BACKGROUND: Placement of an interatrial shunt device reduces pulmonary capillary wedge pressure during exercise in patients with heart failure and preserved or mildly reduced ejection fraction. We aimed to investigate whether an interatrial shunt can reduce heart failure events or improve health status in these patients. METHODS: In this randomised, international, blinded, sham-controlled trial performed at 89 health-care centres, we included patients (aged ≥40 years) with symptomatic heart failure, an ejection fraction of at least 40%, and pulmonary capillary wedge pressure during exercise of at least 25 mm Hg while exceeding right atrial pressure by at least 5 mm Hg. Patients were randomly assigned (1:1) to receive either a shunt device or sham procedure. Patients and outcome assessors were masked to randomisation. The primary endpoint was a hierarchical composite of cardiovascular death or non-fatal ischemic stroke at 12 months, rate of total heart failure events up to 24 months, and change in Kansas City Cardiomyopathy Questionnaire overall summary score at 12 months. Pre-specified subgroup analyses were conducted for the heart failure event endpoint. Analysis of the primary endpoint, all other efficacy endpoints, and safety endpoints was conducted in the modified intention-to-treat population, defined as all patients randomly allocated to receive treatment, excluding those found to be ineligible after randomisation and therefore not treated. This study is registered with ClinicalTrials.gov, NCT03088033. FINDINGS: Between May 25, 2017, and July 24, 2020, 1072 participants were enrolled, of whom 626 were randomly assigned to either the atrial shunt device (n=314) or sham procedure (n=312). There were no differences between groups in the primary composite endpoint (win ratio 1·0 [95% CI 0·8-1·2]; p=0·85) or in the individual components of the primary endpoint. The prespecified subgroups demonstrating a differential effect of atrial shunt device treatment on heart failure events were pulmonary artery systolic pressure at 20W of exercise (pinteraction=0·002 [>70 mm Hg associated with worse outcomes]), right atrial volume index (pinteraction=0·012 [≥29·7 mL/m2, worse outcomes]), and sex (pinteraction=0·02 [men, worse outcomes]). There were no differences in the composite safety endpoint between the two groups (n=116 [38%] for shunt device vs n=97 [31%] for sham procedure; p=0·11). INTERPRETATION: Placement of an atrial shunt device did not reduce the total rate of heart failure events or improve health status in the overall population of patients with heart failure and ejection fraction of greater than or equal to 40%. FUNDING: Corvia Medical.


Assuntos
Cateterismo Cardíaco , Insuficiência Cardíaca , Adulto , Cateterismo Cardíaco/instrumentação , Flavinas , Átrios do Coração/cirurgia , Insuficiência Cardíaca/fisiopatologia , Humanos , Luciferases , Masculino , Volume Sistólico
20.
JACC Heart Fail ; 10(2): 119-128, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-35115085

RESUMO

OBJECTIVES: This study assessed changes in B-type natriuretic peptide (BNP) among patients with heart failure with reduced ejection fraction (HFrEF) treated with sacubitril/valsartan (Sac/Val) according to standard prescribing information. BACKGROUND: Through inhibition of neprilysin, Sac/Val may increase BNP concentrations. METHODS: In an individual patient analysis from the EVALUATE-HF (Study of Effects of Sacubitril/Valsartan vs. Enalapril on Aortic Stiffness in Patients With Mild to Moderate HF With Reduced Ejection Fraction) (n = 221) and the PROVE-HF (Effects of Sacubitril/Valsartan Therapy on Biomarkers, Myocardial Remodeling and Outcomes) (n = 146) studies, we examined changes in BNP, N-terminal pro-BNP (NT-proBNP), and urinary cyclic guanosine monophosphate (ucGMP) from baseline to week 4 and week 12. RESULTS: Median (IQRs) concentration of BNP at baseline, week 4, and week 12 were 145 [IQR: 55-329], 136 [IQR: 50-338], and 135 [IQR: 51-299] ng/L, respectively. There was no significant change from baseline to week 4 (0% [-30% to +41%]; P = 0.36) or week 12 (+1% [-36% to +50%]; P = 0.97). By week 12, one-half of the study participants had a BNP decline. There was no association between Sac/Val dose and BNP changes. Change in BNP was directly associated with change in NT-proBNP (rho: = 0.81; P < 0.001), which decreased by -30% (-50% to -8%) and -32% (-54% to -1%) to weeks 4 and 12 (P < 0.001 for both). In contrast, change in BNP was only weakly associated with change in ucGMP (rho: = 0.19; P < 0.001). Increases in ucGMP were observed regardless of whether BNP was decreased (+11% [-34% to +115%]), unchanged (+34% [-15% to +205%]), or increased (+57% [-12% to +14%]). CONCLUSIONS: In this pooled analysis of patients with HFrEF with standard indications for Sac/Val treatment, there was no significant overall increase in BNP concentrations, and patients demonstrated increase in ucGMP regardless of the trajectory of BNP change. (Study of Effects of Sacubitril/Valsartan vs. Enalapril on Aortic Stiffness in Patients With Mild to Moderate HF With Reduced Ejection Fraction [EVALUATE-HF]; NCT02874794) (Effects of Sacubitril/Valsartan Therapy on Biomarkers, Myocardial Remodeling and Outcomes [PROVE-HF]; NCT02887183).


Assuntos
Insuficiência Cardíaca , Aminobutiratos/uso terapêutico , Antagonistas de Receptores de Angiotensina/uso terapêutico , Biomarcadores , Compostos de Bifenilo , Diuréticos/uso terapêutico , Combinação de Medicamentos , Enalapril/uso terapêutico , Insuficiência Cardíaca/tratamento farmacológico , Humanos , Peptídeo Natriurético Encefálico/uso terapêutico , Volume Sistólico/fisiologia , Tetrazóis/uso terapêutico , Valsartana/uso terapêutico , Vasodilatadores/uso terapêutico
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