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Importance: Whether protein risk scores derived from a single plasma sample could be useful for risk assessment for atherosclerotic cardiovascular disease (ASCVD), in conjunction with clinical risk factors and polygenic risk scores, is uncertain. Objective: To develop protein risk scores for ASCVD risk prediction and compare them to clinical risk factors and polygenic risk scores in primary and secondary event populations. Design, Setting, and Participants: The primary analysis was a retrospective study of primary events among 13â¯540 individuals in Iceland (aged 40-75 years) with proteomics data and no history of major ASCVD events at recruitment (study duration, August 23, 2000 until October 26, 2006; follow-up through 2018). We also analyzed a secondary event population from a randomized, double-blind lipid-lowering clinical trial (2013-2016), consisting of individuals with stable ASCVD receiving statin therapy and for whom proteomic data were available for 6791 individuals. Exposures: Protein risk scores (based on 4963 plasma protein levels and developed in a training set in the primary event population); polygenic risk scores for coronary artery disease and stroke; and clinical risk factors that included age, sex, statin use, hypertension treatment, type 2 diabetes, body mass index, and smoking status at the time of plasma sampling. Main Outcomes and Measures: Outcomes were composites of myocardial infarction, stroke, and coronary heart disease death or cardiovascular death. Performance was evaluated using Cox survival models and measures of discrimination and reclassification that accounted for the competing risk of non-ASCVD death. Results: In the primary event population test set (4018 individuals [59.0% women]; 465 events; median follow-up, 15.8 years), the protein risk score had a hazard ratio (HR) of 1.93 per SD (95% CI, 1.75 to 2.13). Addition of protein risk score and polygenic risk scores significantly increased the C index when added to a clinical risk factor model (C index change, 0.022 [95% CI, 0.007 to 0.038]). Addition of the protein risk score alone to a clinical risk factor model also led to a significantly increased C index (difference, 0.014 [95% CI, 0.002 to 0.028]). Among White individuals in the secondary event population (6307 participants; 432 events; median follow-up, 2.2 years), the protein risk score had an HR of 1.62 per SD (95% CI, 1.48 to 1.79) and significantly increased C index when added to a clinical risk factor model (C index change, 0.026 [95% CI, 0.011 to 0.042]). The protein risk score was significantly associated with major adverse cardiovascular events among individuals of African and Asian ancestries in the secondary event population. Conclusions and Relevance: A protein risk score was significantly associated with ASCVD events in primary and secondary event populations. When added to clinical risk factors, the protein risk score and polygenic risk score both provided statistically significant but modest improvement in discrimination.
Assuntos
Aterosclerose , Doenças Cardiovasculares , Proteômica , Feminino , Humanos , Masculino , Aterosclerose/epidemiologia , Aterosclerose/genética , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/epidemiologia , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Estudos Retrospectivos , Acidente Vascular Cerebral , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/etiologia , Doenças Cardiovasculares/mortalidade , Doenças Cardiovasculares/terapia , Medição de Risco , Adulto , Pessoa de Meia-Idade , Idoso , Islândia/epidemiologia , Ensaios Clínicos Controlados Aleatórios como AssuntoRESUMO
BACKGROUND: U.S. guidelines recommend consideration of sacubitril/valsartan in chronic heart failure (HF) and mildly reduced or preserved ejection fraction (EF). Whether initiation is safe and effective in EF >40% after a worsening heart failure (WHF) event is unknown. OBJECTIVES: PARAGLIDE-HF (Prospective comparison of ARNI with ARB Given following stabiLization In DEcompensated HFpEF) assessed sacubitril/valsartan vs valsartan in EF >40% following a recent WHF event. METHODS: PARAGLIDE-HF is a double-blind, randomized controlled trial of sacubitril/valsartan vs valsartan in patients with EF >40% enrolled within 30 days of a WHF event. The primary endpoint was time-averaged proportional change in amino terminal pro-B-type natriuretic peptide (NT-proBNP) from baseline through Weeks 4 and 8. A secondary hierarchical outcome (win ratio) consisted of: 1) cardiovascular death; 2) HF hospitalizations; 3) urgent HF visits; and 4) change in NT-proBNP. RESULTS: In 466 patients (233 sacubitril/valsartan; 233 valsartan), time-averaged reduction in the NT-proBNP was greater with sacubitril/valsartan (ratio of change: 0.85; 95% CI: 0.73-0.999; P = 0.049). The hierarchical outcome favored sacubitril/valsartan but was not significant (unmatched win ratio: 1.19; 95% CI: 0.93-1.52; P = 0.16). Sacubitril/valsartan reduced worsening renal function (OR: 0.61; 95% CI: 0.40-0.93) but increased symptomatic hypotension (OR: 1.73; 95% CI: 1.09-2.76). There was evidence of a larger treatment effect in the subgroup with EF ≤60% for NT-proBNP change (0.78; 95% CI: 0.61-0.98) and the hierarchical outcome (win ratio: 1.46; 95% CI: 1.09-1.95). CONCLUSIONS: Among patients with EF >40% stabilized after WHF, sacubitril/valsartan led to greater reduction in plasma NT-proBNP levels and was associated with clinical benefit compared with valsartan alone, despite more symptomatic hypotension. (Prospective comparison of ARNI with ARB Given following stabiLization In DEcompensated HFpEF; NCT03988634).
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Insuficiência Cardíaca , Hipotensão , Humanos , Neprilisina/uso terapêutico , Angiotensinas/farmacologia , Angiotensinas/uso terapêutico , Antagonistas de Receptores de Angiotensina/uso terapêutico , Antagonistas de Receptores de Angiotensina/farmacologia , Volume Sistólico , Tetrazóis/uso terapêutico , Tetrazóis/farmacologia , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Valsartana/uso terapêutico , Aminobutiratos/uso terapêutico , Aminobutiratos/farmacologia , Compostos de Bifenilo/uso terapêutico , Hipotensão/induzido quimicamente , Hipotensão/tratamento farmacológico , Combinação de MedicamentosRESUMO
AIMS: To describe outcomes associated with bridging strategies in patients with acute decompensated heart failure-related cardiogenic shock (ADHF-CS) bridged to durable left ventricular assist device (LVAD) or heart transplantation (HTx). METHODS AND RESULTS: Durable LVAD or HTx recipients from 2014 to 2019 with pre-operative ADHF-CS were identified in the Society of Thoracic Surgeons Adult Cardiac Surgery Database and stratified by bridging strategy. The primary outcome was operative or 30-day post-operative mortality. Secondary outcomes included post-operative major bleeding. Exploratory comparisons between bridging strategies and outcomes were performed using overlap weighting with and without covariate adjustment. Among 9783 patients with pre-operative CS, 8777 (89.7%) had ADHF-CS. Medical therapy (n = 5013) was the most common bridging strategy, followed by intra-aortic balloon pump (IABP; n = 2816), catheter-based temporary mechanical circulatory support (TMCS; n = 417), and veno-arterial extracorporeal membrane oxygenation (VA-ECMO; n = 465). Mortality was highest in patients bridged with VA-ECMO (22%), followed by catheter-based TMCS (10%), IABP (9%), and medical therapy (7%). Adverse post-operative outcomes were more frequent in LVAD recipients compared with HTx recipients. CONCLUSION: Among patients with ADHF-CS bridged to HTx or durable LVAD, the highest rates of death and adverse events during index hospitalization were observed in those bridged with VA-ECMO, followed by catheter-based TMCS, IABP, and medical therapy. Patients who received durable LVAD had higher rates of post-operative complications compared with HTx recipients. Prospective trials are needed to define optimal bridging strategies in patients with ADHF-CS.
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Insuficiência Cardíaca , Transplante de Coração , Coração Auxiliar , Adulto , Humanos , Choque Cardiogênico/etiologia , Choque Cardiogênico/terapia , Insuficiência Cardíaca/complicações , Insuficiência Cardíaca/terapia , Estudos Prospectivos , Transplante de Coração/efeitos adversos , Coração Auxiliar/efeitos adversos , Balão Intra-Aórtico/métodos , Resultado do Tratamento , Estudos RetrospectivosRESUMO
BACKGROUND: Little is known about the prevalence and post-surgical outcomes associated with cardiac intensive care unit (CICU) therapeutics among CICU patients referred for cardiac surgery. OBJECTIVES: The purpose of this study was to investigate the clinical characteristics and outcomes of CICU patients referred for cardiac surgery from the intensive care unit. METHODS: We analyzed characteristics and outcomes of CICU admissions referred from the CICU for cardiac surgery during 2017 to 2020 across 29 centers. The primary outcome was in-hospital mortality. RESULTS: Among 10,321 CICU admissions, 887 (8.6%) underwent cardiac surgery, including 406 (46%) coronary artery bypass graftings, 201 (23%) transplants or ventricular assist devices, 171 (19%) valve surgeries, and 109 (12%) other procedures. Common indications for CICU admission included shock (33.5%) and respiratory insufficiency (24.9%). Preoperative CICU therapies included vasoactive therapy in 52.2%, mechanical circulatory support in 35.9%, renal replacement in 8.2%, mechanical ventilation in 35.7%, and 17.5% with high-flow nasal cannula or noninvasive positive pressure ventilation. In-hospital mortality was 11.7% among all CICU admissions and 9.1% among patients treated with cardiac surgery. After multivariable adjustment, pre-op mechanical circulatory support and renal replacement therapy were associated with mortality, while respiratory support and vasoactive therapy were not. CONCLUSIONS: Nearly 1 in 12 contemporary CICU patients receive cardiac surgery. Despite high preoperative disease severity, CICU admissions undergoing cardiac surgery had a comparable mortality rate to CICU patients overall; highlighting the ability of clinicians to select higher acuity patients with a reasonable perioperative risk.
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BACKGROUND: Biomarkers are known to predict major adverse cardiovascular events. However, the association of biomarkers with complex coronary revascularization procedures or high-risk coronary anatomy at the time of revascularization is not understood. OBJECTIVES: We examined the associations between baseline biomarkers and major coronary events (MCE) and complex revascularization procedures. METHODS: FOURIER was a randomized trial of the proprotein convertase subtilisin-kexin type 9 inhibitor evolocumab vs placebo in 27,564 patients with stable atherosclerosis. We analyzed adjusted associations among the biomarkers, MCE (coronary death, myocardial infarction, or revascularization), and complex revascularization (coronary artery bypass graft or complex percutaneous coronary intervention) using a multimarker score with 1 point assigned for each elevated biomarker (high-sensitivity C-reactive protein ≥2 mg/L; N-terminal pro-B-type natriuretic peptide ≥450 pg/mL; high-sensitivity troponin I ≥6 ng/L; growth-differentiation factor-15 ≥1,800 pg/mL). RESULTS: When patients were grouped by the number of elevated biomarkers (0 biomarkers, n = 6,444; 1-2 biomarkers, n = 12,439; ≥3 biomarkers, n = 2,761), there was a significant graded association between biomarker score and the risk of MCE (intermediate score: HRadj: 1.57 [95% CI: 1.38-1.78]; high score: HRadj: 2.90 [95% CI: 2.47-3.40]), and for complex revascularization (intermediate: HRadj: 1.33 [95% CI: 1.06-1.67]; high score: HRadj: 2.07 [95% CI: 1.52-2.83]) and its components (Ptrend <0.05 for each). The number of elevated biomarkers also correlated with the presence of left main disease, multivessel disease, or chronic total occlusion at the time of revascularization (P < 0.05 for each). CONCLUSIONS: A biomarker-based strategy identifies stable patients at risk for coronary events, including coronary artery bypass graft surgery and complex percutaneous coronary intervention, and predicts high-risk coronary anatomy at the time of revascularization. These findings provide insight into the relationships between cardiovascular biomarkers, coronary anatomical complexity, and incident clinical events. (Further Cardiovascular Outcomes Research With PCSK9 Inhibition in Subjects With Elevated Risk [FOURIER]; NCT01764633).
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Anticolesterolemiantes , Doença da Artéria Coronariana , Intervenção Coronária Percutânea , Anticolesterolemiantes/uso terapêutico , Biomarcadores , Doença da Artéria Coronariana/induzido quimicamente , Doença da Artéria Coronariana/diagnóstico , Doença da Artéria Coronariana/cirurgia , Humanos , Pró-Proteína Convertase 9 , Fatores de Risco , Resultado do TratamentoRESUMO
BACKGROUND: Iron deficiency is common in heart failure and associated with worse outcomes. We examined the prevalence and consequences of iron deficiency in the DAPA-HF trial (Dapagliflozin and Prevention of Adverse-Outcomes in Heart Failure) and the effect of dapagliflozin on markers of iron metabolism. We also analyzed the effect of dapagliflozin on outcomes, according to iron status at baseline. METHODS: Iron deficiency was defined as a ferritin level <100 ng/mL or a transferrin saturation <20% and a ferritin level 100 to 299 ng/mL. Additional biomarkers of iron metabolism, including soluble transferrin receptor, erythropoietin, and hepcidin were measured at baseline and 12 months after randomization. The primary outcome was a composite of worsening heart failure (hospitalization or urgent visit requiring intravenous therapy) or cardiovascular death. RESULTS: Of the 4744 patients randomized in DAPA-HF, 3009 had ferritin and transferrin saturation measurements available at baseline, and 1314 of these participants (43.7%) were iron deficient. The rate of the primary outcome was higher in patients with iron deficiency (16.6 per 100 person-years) compared with those without (10.4 per 100 person-years; P<0.0001). The effect of dapagliflozin on the primary outcome was consistent in iron-deficient compared with iron-replete patients (hazard ratio, 0.74 [95% CI, 0.58-0.92] versus 0.81 [95% CI, 0.63-1.03]; P-interaction=0.59). Similar findings were observed for cardiovascular death, heart failure hospitalization, and all-cause mortality. Transferrin saturation, ferritin, and hepcidin were reduced and total iron-binding capacity and soluble transferrin receptor increased with dapagliflozin compared with placebo. CONCLUSIONS: Iron deficiency was common in DAPA-HF and associated with worse outcomes. Dapagliflozin appeared to increase iron use but improved outcomes, irrespective of iron status at baseline. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT03036124.
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Insuficiência Cardíaca , Deficiências de Ferro , Compostos Benzidrílicos , Biomarcadores , Ferritinas , Glucosídeos , Insuficiência Cardíaca/complicações , Insuficiência Cardíaca/tratamento farmacológico , Insuficiência Cardíaca/epidemiologia , Hepcidinas , Humanos , Ferro , Receptores da Eritropoetina/uso terapêutico , Receptores da Transferrina , Volume Sistólico , Transferrinas/farmacologia , Transferrinas/uso terapêuticoRESUMO
AIMS: Blood uric acid (UA) levels are frequently elevated in patients with heart failure and reduced ejection fraction (HFrEF), may lead to gout and are associated with worse outcomes. Reduction in UA is desirable in HFrEF and sodium-glucose cotransporter 2 inhibitors may have this effect. We aimed to examine the association between UA and outcomes, the effect of dapagliflozin according to baseline UA level, and the effect of dapagliflozin on UA in patients with HFrEF in the DAPA-HF trial. METHODS AND RESULTS: The association between UA and the primary composite outcome of cardiovascular death or worsening heart failure, its components, and all-cause mortality was examined using Cox regression analyses among 3119 patients using tertiles of UA, after adjustment for other prognostic variables. Change in UA from baseline over 12 months was also evaluated. Patients in tertile 3 (UA ≥6.8 mg/dl) versus tertile 1 (<5.4 mg/dl) were younger (66.3 ± 10.8 vs. 68 ± 10.2 years), more often male (83.1% vs. 71.5%), had lower estimated glomerular filtration rate (58.2 ± 17.4 vs. 70.6 ± 18.7 ml/min/1.73 m2 ), and more often treated with diuretics. Higher UA was associated with a greater risk of the primary outcome (adjusted hazard ratio tertile 3 vs. tertile 1: 1.32, 95% confidence interval [CI] 1.06-1.66; p = 0.01). The risk of heart failure hospitalization and cardiovascular death increased by 7% and 6%, respectively per 1 mg/dl unit increase of UA (p = 0.04 and p = 0.07). Spline analysis revealed a linear increase in risk above a cut-off UA value of 7.09 mg/dl. Compared with placebo, dapagliflozin reduced UA by 0.84 mg/dl (95% CI -0.93 to -0.74) over 12 months (p < 0.001). Dapagliflozin improved outcomes, irrespective of baseline UA concentration. CONCLUSION: Uric acid remains an independent predictor of worse outcomes in a well-treated contemporary HFrEF population. Compared with placebo, dapagliflozin reduced UA and improved outcomes irrespective of UA concentration.
Assuntos
Insuficiência Cardíaca , Disfunção Ventricular Esquerda , Idoso , Compostos Benzidrílicos , Feminino , Glucosídeos/farmacologia , Insuficiência Cardíaca/complicações , Humanos , Masculino , Pessoa de Meia-Idade , Volume Sistólico , Ácido Úrico , Disfunção Ventricular Esquerda/complicaçõesRESUMO
Prolonged use of dual antiplatelet therapy (DAPT) post-percutaneous coronary intervention (PCI) has been shown to reduce the risk of major adverse cardiovascular events (MACE), but with increased bleeding. It remains unknown whether biomarkers of platelet activation may be useful for identifying patients at increased risk of MACE. The DAPT study was a randomized trial of 12 versus 30 months of DAPT in patients who underwent PCI. Serum biomarkers [myeloid-related protein (MRP)-8/14, P-selectin, soluble CD-40 ligand (sCD40L)] were assessed in 1399 patients early post-PCI. On-treatment platelet reactivity index (PRI) using VASP phosphorylation was assessed in 443 patients randomized to continued DAPT at 1 year. MACE was defined as CV death, MI, or ischemic stroke. Multivariable models were adjusted for baseline characteristics, index event, and stent type. A stepwise increase in the risk of MACE was observed with increasing tertiles of both MRP-8/14 and P-selectin (p-trend = 0.04 for both). After multivariable adjustment, the adjusted HR (95% CI) for MACE in patients in the top tertile was 1.94 (1.14-3.30) for MRP-8/14 and 1.62 (0.99-2.64) for P-selectin. In contrast, baseline sCD40L was not associated with CV risk. Among patients randomized to continued DAPT, higher on-treatment platelet reactivity was not significantly associated with risk of MACE (p-trend = 0.32; adj-HR T3 vs. T1 1.54, 95% CI 0.20-12.18) or bleeding (P-trend = 0.17; adj-HR 0.25, 95% CI 0.05-1.21). MRP-8/14 and soluble P-selectin may be useful for identifying patients at increased risk of MACE after PCI. The utility of on-treatment platelet function testing requires further study.Clinical Trial Registration https://www.clinicaltrials.gov . Unique identifier NCT00977938.
Assuntos
Calgranulina A/sangue , Calgranulina B/sangue , Reestenose Coronária , Hemorragia , Selectina-P/sangue , Intervenção Coronária Percutânea/efeitos adversos , Biomarcadores/sangue , Ligante de CD40/sangue , Reestenose Coronária/sangue , Reestenose Coronária/etiologia , Reestenose Coronária/prevenção & controle , Monitoramento de Medicamentos/métodos , Terapia Antiplaquetária Dupla/efeitos adversos , Terapia Antiplaquetária Dupla/métodos , Duração da Terapia , Feminino , Hemorragia/sangue , Hemorragia/induzido quimicamente , Hemorragia/prevenção & controle , Humanos , Masculino , Pessoa de Meia-Idade , Intervenção Coronária Percutânea/instrumentação , Intervenção Coronária Percutânea/métodos , Testes de Função Plaquetária/métodos , Reprodutibilidade dos Testes , Medição de Risco/métodosRESUMO
OBJECTIVES: This study compared the efficacy and safety of sacubitril/valsartan to enalapril in Black and non-Black Americans with acute decompensated heart failure (ADHF). BACKGROUND: Black patients have a different response to treatment with angiotensin-converting enzyme inhibitors compared with other racial and ethnic groups. How Black patients with ADHF respond to sacubitril/valsartan, an angiotensin receptor-neprilysin inhibitor, is unclear. PIONEER-HF was a double-blind randomized clinical trial of sacubitril/valsartan versus enalapril in hospitalized patients with ADHF following hemodynamic stabilization. METHODS: In a pre-specified subgroup analysis, we examined changes in N-terminal pro-B-type natriuretic peptide, clinical outcomes, and safety according to race. RESULTS: The study population, all enrolled in the United States, included 316 (36%) Black participants, 515 (58%) White participants, and 50 (5.7%) participants of other racial groups. The reduction in N-terminal pro-B-type natriuretic peptide concentration at weeks 4 and 8 was significantly greater with sacubitril/valsartan than enalapril in both Black (ratio of change with sacubitril/valsartan vs. enalapril: 0.71; 95% confidence interval [CI]: 0.58 to 0.88) and non-Black patients (ratio of change: 0.71; 95% CI: 0.61 to 0.83; interaction p = 1.00). Compared with enalapril, sacubitril/valsartan also reduced the pre-specified exploratory composite of cardiovascular death or HF rehospitalization in both Black (hazard ratio: 0.47; 95% CI: 0.24 to 0.93) and non-Black patients (hazard ratio: 0.65; 95% CI: 0.40 to 1.06; interaction p = 0.44). CONCLUSIONS: Among Black patients admitted with ADHF in the United States, the in-hospital initiation of sacubitril/valsartan was more effective than enalapril in reducing natriuretic peptide levels and the composite of cardiovascular death or HF rehospitalization. The effect of sacubitril/valsartan did not differ by race. (Comparison of Sacubitril/Valsartan Versus Enalapril on Effect on NT-proBNP in Patients Stabilized From an Acute Heart Failure Episode [PIONEER-HF]; NCT02554890).
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Aminobutiratos , Antagonistas de Receptores de Angiotensina , Compostos de Bifenilo , Enalapril , Insuficiência Cardíaca , Neprilisina , Valsartana , Negro ou Afro-Americano , Aminobutiratos/uso terapêutico , Antagonistas de Receptores de Angiotensina/uso terapêutico , Angiotensinas , Compostos de Bifenilo/uso terapêutico , Combinação de Medicamentos , Enalapril/uso terapêutico , Insuficiência Cardíaca/tratamento farmacológico , Insuficiência Cardíaca/etnologia , Humanos , Valsartana/uso terapêuticoRESUMO
BACKGROUND: The PIONEER-HF (comParIson Of sacubitril/valsartaN versus Enalapril on Effect on nt-pRo-bnp in patients stabilized from an acute Heart Failure episode) trial demonstrated the efficacy and safety of sacubitril/valsartan (S/V) in stabilized patients with acute decompensated heart failure (HF) and reduced ejection fraction. OBJECTIVES: The study sought to determine whether and how prior HF history and treatment with an angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) affected the results. METHODS: The PIONEER-HF trial was a prospective, multicenter, double-blind, randomized clinical trial enrolling 881 patients with an ejection fraction ≤40%. Patients were randomly assigned 1:1 to in-hospital initiation of S/V (n = 440) versus enalapril (n = 441). Pre-specified subgroup analyses were performed based on prior HF history (i.e., de novo HF vs. worsening chronic HF) and treatment with an ACE inhibitor or ARB (i.e., ACE inhibitor or ARB-yes vs. ACE inhibitor or ARB-no) at admission. RESULTS: At enrollment, 303 (34%) patients presented with de novo HF and 576 (66%) patients with worsening chronic HF. A total of 421 (48%) patients had been treated with an ACE inhibitor or ARB, while 458 (52%) had not been treated with an ACE inhibitor or ARB. N-terminal pro-B-type natriuretic peptide declined significantly in all 4 subgroups (p < 0.001), with greater decreases in the S/V versus the enalapril arm (p < 0.001). There was no interaction between prior HF history (p = 0.350) or ACE inhibitor or ARB treatment (p = 0.880) and the effect of S/V versus enalapril on cardiovascular death or rehospitalization for HF. The incidences of adverse events were comparable between S/V and enalapril across all 4 subgroups. CONCLUSIONS: Among patients admitted for acute decompensated HF, S/V was safe and well tolerated, led to a significantly greater reduction in N-terminal pro-B-type natriuretic peptide, and improved clinical outcomes compared with enalapril irrespective of previous HF history or ACE inhibitor or ARB treatment. (Comparison of Sacubitril/Valsartan Versus Enalapril on Effect of NT-proBNP in Patients Stabilized From an Acute Heart Failure Episode [PIONEER-HF]; NCT02554890).
Assuntos
Antagonistas de Receptores de Angiotensina/administração & dosagem , Inibidores da Enzima Conversora de Angiotensina/administração & dosagem , Insuficiência Cardíaca/tratamento farmacológico , Insuficiência Cardíaca/mortalidade , Neprilisina/antagonistas & inibidores , Sistema Renina-Angiotensina/efeitos dos fármacos , Idoso , Aminobutiratos/administração & dosagem , Compostos de Bifenilo , Morte , Método Duplo-Cego , Combinação de Medicamentos , Enalapril/administração & dosagem , Feminino , Insuficiência Cardíaca/fisiopatologia , Humanos , Masculino , Pessoa de Meia-Idade , Neprilisina/fisiologia , Estudos Prospectivos , Receptores de Angiotensina/fisiologia , Sistema Renina-Angiotensina/fisiologia , Tetrazóis/administração & dosagem , ValsartanaRESUMO
Although coronavirus disease 2019 (COVID-19) predominantly disrupts the respiratory system, there is accumulating experience that the disease, particularly in its more severe manifestations, also affects the cardiovascular system. Cardiovascular risk factors and chronic cardiovascular conditions are prevalent among patients affected by COVID-19 and associated with adverse outcomes. However, whether pre-existing cardiovascular disease is an independent determinant of higher mortality risk with COVID-19 remains uncertain. Acute cardiac injury, manifest by increased blood levels of cardiac troponin, electrocardiographic abnormalities, or myocardial dysfunction, occurs in up to ~60% of hospitalized patients with severe COVID-19. Potential contributors to acute cardiac injury in the setting of COVID-19 include (1) acute changes in myocardial demand and supply due to tachycardia, hypotension, and hypoxemia resulting in type 2 myocardial infarction; (2) acute coronary syndrome due to acute atherothrombosis in a virally induced thrombotic and inflammatory milieu; (3) microvascular dysfunction due to diffuse microthrombi or vascular injury; (4) stress-related cardiomyopathy (Takotsubo syndrome); (5) nonischemic myocardial injury due to a hyperinflammatory cytokine storm; or (6) direct viral cardiomyocyte toxicity and myocarditis. Diffuse thrombosis is emerging as an important contributor to adverse outcomes in patients with COVID-19. Practitioners should be vigilant for cardiovascular complications of COVID-19. Monitoring may include serial cardiac troponin and natriuretic peptides, along with fibrinogen, D-dimer, and inflammatory biomarkers. Management decisions should rely on the clinical assessment for the probability of ongoing myocardial ischemia, as well as alternative nonischemic causes of injury, integrating the level of suspicion for COVID-19.
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Betacoronavirus , Doenças Cardiovasculares/complicações , Infecções por Coronavirus/complicações , Pneumonia Viral/complicações , Monofosfato de Adenosina/análogos & derivados , Monofosfato de Adenosina/uso terapêutico , Alanina/análogos & derivados , Alanina/uso terapêutico , Antimaláricos/uso terapêutico , Antivirais/uso terapêutico , Betacoronavirus/imunologia , Betacoronavirus/patogenicidade , Biomarcadores/sangue , COVID-19 , Cloroquina/uso terapêutico , Infecções por Coronavirus/tratamento farmacológico , Humanos , Hidroxicloroquina/uso terapêutico , Hipóxia/complicações , Pandemias , Plasma/imunologia , Pneumonia Viral/tratamento farmacológico , Receptor Tipo 2 de Angiotensina/metabolismo , Fatores de Risco , SARS-CoV-2 , Cardiomiopatia de Takotsubo/etiologia , Internalização do VírusRESUMO
INTRODUCTION: Extracorporeal membrane oxygenation (ECMO) is a life-saving technology capable of restoring perfusion but is not without significant complications that limit its realizable therapeutic benefit. ECMO-induced hemodynamics increase cardiac afterload risking left ventricular distention and impaired cardiac recovery. To mitigate potentially harmful effects, multiple strategies to unload the left ventricle (LV) are used in clinical practice but data supporting the optimal approach is presently lacking. MATERIALS & METHODS: We reviewed outcomes of our ECMO population from September 2015 through January 2019 to determine if our LV unloading strategies were associated with patient outcomes. We compared reactive (Group 1, n = 30) versus immediate (Group 2, n = 33) LV unloading and then compared patients unloaded with an Impella CP (n = 19) versus an intra-aortic balloon pump (IABP, n = 16), analyzing survival and ECMO-related complications. RESULTS: Survival was similar between Groups 1 and 2 (33 vs 42%, P = .426) with Group 2 experiencing more clinically-significant hemorrhage (40 vs. 67%, P = .034). Survival and ECMO-related complications were similar between patients unloaded with an Impella versus an IABP. However, the Impella group exhibited a higher rate of survival (37%) than predicted by their median SAVE score (18%). DISCUSSION: Based on this analysis, reactive unloading appears to be a viable strategy while venting with the Impella CP provides better than anticipated survival. Our findings correlate with recent large cohort studies and motivate further work to design clinical guidelines and future trial design.
Assuntos
Oxigenação por Membrana Extracorpórea/efeitos adversos , Coração Auxiliar , Balão Intra-Aórtico , Disfunção Ventricular Esquerda/etiologia , Disfunção Ventricular Esquerda/terapia , Idoso , Feminino , Hemodinâmica , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Taxa de Sobrevida , Resultado do Tratamento , Disfunção Ventricular Esquerda/mortalidade , Disfunção Ventricular Esquerda/fisiopatologiaRESUMO
Background Trimethylamine N-oxide (TMAO) may have prothrombotic properties. We examined the association of TMAO quartiles with major adverse cardiovascular events (MACE) and the effect of TMAO on the efficacy of ticagrelor. Methods and Results PEGASUS-TIMI 54 (Prevention of Cardiovascular Events in Patients With Prior Heart Attack Using Ticagrelor Compared to Placebo on a Background of Aspirin - Thrombolysis in Myocardial Infarction 54) randomized patients with prior myocardial infarction to ticagrelor or placebo (median follow-up 33 months). Baseline plasma concentrations of TMAO were measured in a nested case-control study of 597 cases with cardiovascular death, myocardial infarction, or stroke (MACE) and 1206 controls matched for age, sex, and estimated glomerular filtration rate [eGFR]. Odds ratios (OR) were used for the association between TMAO quartiles and MACE, adjusting for baseline clinical characteristics (age, sex, eGFR, region, body mass index, hypertension, hypercholesterolemia, diabetes mellitus, smoking, peripheral artery disease, index event, aspirin dosage and treatment arm), and cardiovascular biomarkers (hs-TnT [high-sensitivity troponin T], hs-CRP [high-sensitivity C-reactive protein], NT-proBNP [N-terminal-pro-B-type natriuretic peptide]). Higher TMAO quartiles were associated with risk of MACE (OR for quartile 4 versus quartile 1, 1.43, 95% CI, 1.06-1.93, P trend=0.015). The association was driven by cardiovascular death (OR 2.25, 95% CI, 1.28-3.96, P trend=0.003) and stroke (OR 2.68, 95% CI, 1.39-5.17, P trend<0.001). After adjustment for clinical factors, the association persisted for cardiovascular death (ORadj 1.89, 95% CI, 1.03-3.45, P trend=0.027) and stroke (ORadj 2.01, 95% CI, 1.01-4.01, P trend=0.022), but was slightly attenuated after adjustment for cardiovascular biomarkers (cardiovascular death: ORadj 1.74, 95% CI, 0.88-3.45, P trend=0.079; and stroke: ORadj 1.82, 95% CI, 0.88-3.78, P trend=0.056). The reduction in MACE with ticagrelor was consistent across TMAO quartiles (P interaction=0.92). Conclusions Among patients with prior myocardial infarction, higher TMAO levels were associated with cardiovascular death and stroke but not with recurrent myocardial infarction. The efficacy of ticagrelor was consistent regardless of TMAO levels. Registration URL: https://www.cliniâcaltrâials.gov; Unique identifiers: PEGASUS-TIMI 54, NCT01225562.
Assuntos
Bactérias/metabolismo , Terapia Antiplaquetária Dupla , Microbioma Gastrointestinal , Intestinos/microbiologia , Metilaminas/sangue , Infarto do Miocárdio/tratamento farmacológico , Inibidores da Agregação Plaquetária/uso terapêutico , Ticagrelor/uso terapêutico , Idoso , Aspirina/uso terapêutico , Estudos de Casos e Controles , Terapia Antiplaquetária Dupla/efeitos adversos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/sangue , Infarto do Miocárdio/microbiologia , Infarto do Miocárdio/mortalidade , Inibidores da Agregação Plaquetária/efeitos adversos , Ensaios Clínicos Controlados Aleatórios como Assunto , Recidiva , Medição de Risco , Fatores de Risco , Prevenção Secundária , Acidente Vascular Cerebral/sangue , Acidente Vascular Cerebral/mortalidade , Acidente Vascular Cerebral/prevenção & controle , Trombose/sangue , Trombose/mortalidade , Trombose/prevenção & controle , Ticagrelor/efeitos adversos , Fatores de Tempo , Resultado do Tratamento , Estados Unidos , Regulação para CimaRESUMO
Intensive antithrombotic therapy reduces major adverse cardiovascular events (MACE) and major adverse limb events (MALE) in patients with peripheral artery disease (PAD). Recent studies have suggested heterogeneity in risk and benefit in those with and without concomitant coronary artery disease (CAD) and peripheral revascularization. We evaluated the risk of MACE and MALE in patients with PAD stratified by history of concomitant CAD and prior peripheral revascularization and whether the efficacy and safety of vorapaxar were similar in these subgroups. The TRA 2°P-TIMI 50 trial randomized 26,449 patients with prior MI, ischemic stroke, or PAD to vorapaxar or placebo. This analysis examined the effect of vorapaxar in a broad population of 6136 patients with PAD. Overall, vorapaxar significantly reduced MACE (HR 0.85, 95% CI 0.73, 0.99; p = 0.034) and MALE (HR 0.70, 95% CI 0.53, 0.92; p = 0.011) in patients with PAD. The absolute risk reduction (ARR) for MACE was greater in patients with PAD and CAD versus those with PAD alone (-2.2% vs 0.1%: number needed to treat (NNT) 45 vs 1000). Conversely, the ARR for MALE was higher in those with prior lower extremity revascularization (2.5% vs 0.2%: NNT 40 vs 500). Vorapaxar increased major bleeding (HR 1.39, 95% CI 1.12, 1.71; p = 0.003). The net clinical outcome in all patients with PAD was reduced with vorapaxar (HR 0.82, 95% CI 0.72, 0.94; p = 0.004), with benefits driven by reductions in MACE for those with CAD and by reductions in MALE for those with prior peripheral revascularization. Among patients with PAD, vorapaxar resulted in a net clinical benefit; however, the drivers of benefit were heterogeneous, with greater reductions in MACE in those with concomitant CAD and greater reductions in MALE in those with prior lower extremity revascularization, and unclear benefit in patients with neither. These clinical characteristics may be useful in identifying the subgroups of patients with PAD most likely to benefit from potent antithrombotic therapies. ClinicalTrials.gov Identifier: NCT00526474.
Assuntos
Doença da Artéria Coronariana/complicações , Fibrinolíticos/uso terapêutico , Lactonas/uso terapêutico , Doença Arterial Periférica/tratamento farmacológico , Inibidores da Agregação Plaquetária/uso terapêutico , Piridinas/uso terapêutico , Idoso , Doença da Artéria Coronariana/diagnóstico , Doença da Artéria Coronariana/mortalidade , Procedimentos Endovasculares , Feminino , Fibrinolíticos/efeitos adversos , Hemorragia/induzido quimicamente , Humanos , Lactonas/efeitos adversos , Masculino , Pessoa de Meia-Idade , Doença Arterial Periférica/complicações , Doença Arterial Periférica/diagnóstico , Doença Arterial Periférica/mortalidade , Inibidores da Agregação Plaquetária/efeitos adversos , Piridinas/efeitos adversos , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento , Procedimentos Cirúrgicos VascularesRESUMO
Importance: In PIONEER-HF, among stabilized patients with acute decompensated heart failure (ADHF), the in-hospital initiation of sacubitril/valsartan was well tolerated and led to improved outcomes compared with enalapril. However, there are limited data comparing the strategies of in-hospital vs postdischarge initiation of sacubitril/valsartan. Objective: To describe changes in N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels in patients recently hospitalized for ADHF and switching from taking enalapril to taking sacubitril/valsartan after discharge and compare clinical outcomes for patients randomized to receive in-hospital initiation of sacubitril/valsartan vs in-hospital initiation of enalapril who later switched to taking sacubitril/valsartan during an open-label extension phase. Interventions: Sacubitril/valsartan titrated to 97/103 mg twice daily. Design, Setting, and Participants: The PIONEER-HF trial was a multicenter, randomized, double-blind, active-controlled trial conducted at 129 US sites between May 2016 and May 2018 that compared the in-hospital initiation of sacubitril/valsartan vs enalapril (titrated to target dose, 10 mg twice daily) for 8 weeks among patients admitted for ADHF with reduced ejection fraction and hemodynamic stability. All patients were to continue in a 4-week, open-label study of sacubitril/valsartan; of 881 patients enrolled in PIONEER-HF, 832 (94%) continued in the open-label study. Main Outcomes and Measures: Changes in NT-proBNP levels from week 8 to 12 as well as the exploratory composite of heart failure rehospitalization or cardiovascular death from randomization through week 12. Results: Of 881 participants, 226 (27.7%) were women, 487 (58.5%) were white, 297 (35.7%) were black, 15 (1.8%) were Asian, and 73 (8.8%) were of Hispanic ethnicity; the mean (SD) age was 61 (14) years. For patients who continued to take sacubitril/valsartan, NT-proBNP levels declined -17.2% (95% CI, -3.2 to -29.1) from week 8 to 12. The NT-proBNP levels declined to a greater extent for those switching from taking enalapril to sacubitril/valsartan after the week 8 visit (-37.4%; 95% CI, -28.1 to -45.6; P < .001; comparing changes in 2 groups). Over the entire 12 weeks of follow-up, patients that began taking sacubitril/valsartan in the hospital had a lower hazard for the composite outcome compared with patients that initiated enalapril in the hospital and then had a delayed initiation of sacubitril/valsartan 8 weeks later (hazard ratio, 0.69; 95% CI 0.49-0.97). Conclusions and Relevance: Switching patients' treatment from enalapril to sacubitril/valsartan at 8 weeks after randomization led to a further 37% reduction in NT-proBNP levels in patients with heart failure with reduced ejection fraction and a recent hospitalization for ADHF. Trial Registration: ClinicalTrials.gov identifier: NCT02554890.
Assuntos
Aminobutiratos/uso terapêutico , Antagonistas de Receptores de Angiotensina/uso terapêutico , Insuficiência Cardíaca/sangue , Insuficiência Cardíaca/tratamento farmacológico , Peptídeo Natriurético Encefálico/análise , Neprilisina/antagonistas & inibidores , Fragmentos de Peptídeos/análise , Tetrazóis/uso terapêutico , Doença Aguda , Idoso , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Compostos de Bifenilo , Combinação de Medicamentos , Enalapril/uso terapêutico , Feminino , Hospitalização , Humanos , Masculino , Pessoa de Meia-Idade , Alta do Paciente , ValsartanaRESUMO
Background Small studies have suggested an association between markers of collagen turnover and adverse outcomes in heart failure ( HF ). We examined C-terminal telopeptide (beta- CT x) and the risk of cardiovascular death or new or worsening HF in non- ST -elevation acute coronary syndrome. Methods and Results We measured baseline serum beta- CT x, NT -pro BNP (N-terminal pro-B-type natriuretic peptide), hsTnT (high-sensitivity cardiac troponin T) and hs CRP (high-sensitivity C-reactive protein) (Roche Diagnostics) in a nested biomarker analysis (n=4094) from a study of patients with non- ST -elevation acute coronary syndrome. The relationship between quartiles of beta- CT x and cardiovascular death or HF over a median follow-up time of 12 months was analyzed using adjusted Cox models. Higher beta- CT x levels identified a significantly higher risk of cardiovascular death/ HF (Q4 10.9% versus Q1 3.8%, Logrank P<0.001). After multivariable adjustment, beta- CT x in the top quartile (Q4) was associated with cardiovascular death/ HF (Q4 versus Q1: adjusted hazard ratio 2.22 [1.50-3.27]) and its components (Q4 versus Q1: cardiovascular death: adjusted hazard ratio 2.48 [1.46-4.21]; HF : adjusted hazard ratio 2.04 [1.26-3.30]). In an adjusted multimarker model including NT -pro BNP , hsTnT, and hs CRP , beta- CT x remained independently associated with cardiovascular death/ HF (Q4 versus Q1: adjusted hazard ratio 1.98 [1.34-2.93]) and its components. Beta- CT x correlated weakly with NT -pro BNP ( r=0.17, P<0.001) and left ventricular ejection fraction ( r=-0.05, P=0.008) and did not correlate with hsTnT ( r=0.02, P=0.20), or hs CRP ( r=-0.03, P=0.09). Conclusions Levels of beta- CT x, a biomarker of collagen turnover, were associated with cardiovascular death and HF in patients with non- ST -elevation acute coronary syndrome. This biomarker, which correlated only weakly or not significantly with traditional biomarkers of cardiovascular death and HF , may provide complementary pathobiological insight and risk stratification in these patients.
Assuntos
Síndrome Coronariana Aguda/sangue , Colágeno Tipo I/sangue , Infarto do Miocárdio sem Supradesnível do Segmento ST/sangue , Peptídeos/sangue , Síndrome Coronariana Aguda/diagnóstico , Síndrome Coronariana Aguda/mortalidade , Idoso , Biomarcadores/sangue , Proteína C-Reativa/análise , Progressão da Doença , Feminino , Insuficiência Cardíaca/mortalidade , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Peptídeo Natriurético Encefálico/sangue , Infarto do Miocárdio sem Supradesnível do Segmento ST/diagnóstico , Infarto do Miocárdio sem Supradesnível do Segmento ST/mortalidade , Fragmentos de Peptídeos/sangue , Valor Preditivo dos Testes , Prognóstico , Ensaios Clínicos Controlados Aleatórios como Assunto , Medição de Risco , Fatores de Risco , Fatores de Tempo , Troponina T/sangueRESUMO
Background Growth differentiation factor (GDF)-15 has been shown to predict cardiovascular (CV) outcomes in acute coronary syndrome (ACS) using non-commercial assays. We evaluated the prognostic performance of GDF-15 measured with the first clinically available assay. Furthermore, we evaluated whether GDF-15 was associated with CV death or heart failure (HF) across the spectrum of risk in non-ST-segment elevation (NSTE)-ACS. Methods We measured baseline GDF-15 (Roche, Elecsys) in 4330 patients with NSTE-ACS enrolled in MERLIN-TIMI 36. Patients were categorized using a priori thresholds of GDF-15 levels (<1200, 1200-1800, ≥1800 ng/L) and stratified according to estimated clinical risk per TIMI risk score (0-2, 3-4, and ≥5). Cox modeling included age, sex, BMI, smoking, HF, diabetes, renal function, NT-proBNP, hsTnT, and hsCRP. Results There were 2286 (53%), 1104 (25%), and 940 (22%) pts with GDF-15 <1200, 1200-1800, and ≥1800 respectively. GDF-15 was significantly associated after multivariable adjustment with CV death/HF modeled either as a categorical (1200-1800 ng/L: Adj hazard ratios [HR] 1.55 [1.09-2.19]; ≥1800 ng/L: Adj HR 1.94 [1.34-2.79]) or continuous variable (Adj HR 1.36 [1.16-1.60] per 1-unit increase in log2-transformed GDF-15). Notably, there was an interaction (Pinteraction=0.003) between TIMI risk score and GDF-15, with GDF-15 identifying the greatest incremental relative risk in those at lowest risk based on the TIMI risk score alone. Conclusions Using a clinically available assay, GDF-15 can be applied using established cut-off points to independently predict risk of CV death/HF in patients with NSTE-ACS. This incremental risk appears to be particularly robust among individuals traditionally identified as low risk.
Assuntos
Síndrome Coronariana Aguda/patologia , Fator 15 de Diferenciação de Crescimento/sangue , Síndrome Coronariana Aguda/mortalidade , Idoso , Biomarcadores/sangue , Feminino , Insuficiência Cardíaca/mortalidade , Insuficiência Cardíaca/patologia , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Prognóstico , Modelos de Riscos Proporcionais , Fatores de RiscoRESUMO
AIMS: Klotho, an essential co-receptor for fibroblast growth factor (FGF)-23, has potentially beneficial inhibitory effects on the renin-angiotensin system. Limited data exist on the prognostic value of Klotho and FGF-23 levels in combination or their ability to predict benefit from angiotensin-converting enzyme (ACE) inhibition. METHODS AND RESULTS: A total of 3555 patients with stable ischaemic heart disease and left ventricular ejection fraction > 40% enrolled in the PEACE trial of trandolapril vs. placebo had Klotho levels drawn at randomization. Patients were characterized by quartiles of Klotho and FGF-23 concentrations. Six-year Kaplan-Meier rates and adjusted risk were calculated in the placebo arm for the composite of cardiovascular (CV) death or hospitalization for heart failure and its components. Low [quartile (Q) 1-3] Klotho concentration was associated with an increased rate of CV death or hospitalization for heart failure as compared with Q4 (8.2% vs. 4.2%; P = 0.03). After multivariable adjustment for clinical variables and renal and CV biomarkers (estimated glomerular filtration rate, cystatin-C, urine albumin-to-creatinine ratio, FGF-23, high-sensitivity troponin T, N-terminal pro-B-type natriuretic peptide, and high-sensitivity C-reactive protein), low Klotho concentration remained strongly associated with increased risk of CV death or hospitalization for heart failure [adjusted hazard ratio (HR) 2.62; 95% confidence interval (CI) 1.35-5.08; P < 0.01]. The combination of low Klotho and high (Q4) FGF-23 concentration identified patients at particularly elevated risk (adjusted HR 3.99; 95% CI 1.67-9.56; P < 0.01). This high-risk combination additionally predicted benefit from trandolapril (HR 0.39; 95% CI 0.23-0.68; Pinteraction < 0.01). CONCLUSIONS: Low Klotho concentration is associated with an increased risk of CV death or heart failure hospitalization in patients with stable ischaemic heart disease. The combination of low Klotho and high FGF-23 further identifies patients at distinctly elevated risk who derive clinical benefit from the ACE-inhibitor trandolapril.