RESUMO
BACKGROUND: Ferric carboxymaltose therapy reduces symptoms and improves quality of life in patients who have heart failure with a reduced ejection fraction and iron deficiency. Additional evidence about the effects of ferric carboxymaltose on clinical events is needed. METHODS: In this double-blind, randomized trial, we assigned ambulatory patients with heart failure, a left ventricular ejection fraction of 40% or less, and iron deficiency, in a 1:1 ratio, to receive intravenous ferric carboxymaltose or placebo, in addition to standard therapy for heart failure. Ferric carboxymaltose or placebo was given every 6 months as needed on the basis of iron indexes and hemoglobin levels. The primary outcome was a hierarchical composite of death within 12 months after randomization, hospitalizations for heart failure within 12 months after randomization, or change from baseline to 6 months in the 6-minute walk distance. The significance level was set at 0.01. RESULTS: We enrolled 3065 patients, of whom 1532 were randomly assigned to the ferric carboxymaltose group and 1533 to the placebo group. Death by month 12 occurred in 131 patients (8.6%) in the ferric carboxymaltose group and 158 (10.3%) in the placebo group; a total of 297 and 332 hospitalizations for heart failure, respectively, occurred by month 12; and the mean (±SD) change from baseline to 6 months in the 6-minute walk distance was 8±60 and 4±59 m, respectively (Wilcoxon-Mann-Whitney P = 0.02; unmatched win ratio, 1.10; 99% confidence interval, 0.99 to 1.23). Repeated dosing of ferric carboxymaltose appeared to be safe with an acceptable adverse-event profile in the majority of patients. The number of patients with serious adverse events occurring during the treatment period was similar in the two groups (413 patients [27.0%] in the ferric carboxymaltose group and 401 [26.2%] in the placebo group). CONCLUSIONS: Among ambulatory patients who had heart failure with a reduced ejection fraction and iron deficiency, there was no apparent difference between ferric carboxymaltose and placebo with respect to the hierarchical composite of death, hospitalizations for heart failure, or 6-minute walk distance. (Funded by American Regent, a Daiichi Sankyo Group company; HEART-FID ClinicalTrials.gov number, NCT03037931.).
Assuntos
Compostos Férricos , Insuficiência Cardíaca , Deficiências de Ferro , Humanos , Insuficiência Cardíaca/complicações , Insuficiência Cardíaca/tratamento farmacológico , Insuficiência Cardíaca/fisiopatologia , Deficiências de Ferro/complicações , Deficiências de Ferro/tratamento farmacológico , Qualidade de Vida , Volume Sistólico , Função Ventricular Esquerda , Compostos Férricos/administração & dosagem , Compostos Férricos/efeitos adversos , Compostos Férricos/uso terapêutico , Método Duplo-Cego , Administração Intravenosa , Assistência AmbulatorialRESUMO
BACKGROUND: In patients with symptomatic heart failure, sacubitril-valsartan has been found to reduce the risk of hospitalization and death from cardiovascular causes more effectively than an angiotensin-converting-enzyme inhibitor. Trials comparing the effects of these drugs in patients with acute myocardial infarction have been lacking. METHODS: We randomly assigned patients with myocardial infarction complicated by a reduced left ventricular ejection fraction, pulmonary congestion, or both to receive either sacubitril-valsartan (97 mg of sacubitril and 103 mg of valsartan twice daily) or ramipril (5 mg twice daily) in addition to recommended therapy. The primary outcome was death from cardiovascular causes or incident heart failure (outpatient symptomatic heart failure or heart failure leading to hospitalization), whichever occurred first. RESULTS: A total of 5661 patients underwent randomization; 2830 were assigned to receive sacubitril-valsartan and 2831 to receive ramipril. Over a median of 22 months, a primary-outcome event occurred in 338 patients (11.9%) in the sacubitril-valsartan group and in 373 patients (13.2%) in the ramipril group (hazard ratio, 0.90; 95% confidence interval [CI], 0.78 to 1.04; P = 0.17). Death from cardiovascular causes or hospitalization for heart failure occurred in 308 patients (10.9%) in the sacubitril-valsartan group and in 335 patients (11.8%) in the ramipril group (hazard ratio, 0.91; 95% CI, 0.78 to 1.07); death from cardiovascular causes in 168 (5.9%) and 191 (6.7%), respectively (hazard ratio, 0.87; 95% CI, 0.71 to 1.08); and death from any cause in 213 (7.5%) and 242 (8.5%), respectively (hazard ratio, 0.88; 95% CI, 0.73 to 1.05). Treatment was discontinued because of an adverse event in 357 patients (12.6%) in the sacubitril-valsartan group and 379 patients (13.4%) in the ramipril group. CONCLUSIONS: Sacubitril-valsartan was not associated with a significantly lower incidence of death from cardiovascular causes or incident heart failure than ramipril among patients with acute myocardial infarction. (Funded by Novartis; PARADISE-MI ClinicalTrials.gov number, NCT02924727.).
Assuntos
Aminobutiratos/uso terapêutico , Antagonistas de Receptores de Angiotensina/uso terapêutico , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Compostos de Bifenilo/uso terapêutico , Insuficiência Cardíaca/prevenção & controle , Infarto do Miocárdio/tratamento farmacológico , Ramipril/uso terapêutico , Valsartana/uso terapêutico , Idoso , Aminobutiratos/efeitos adversos , Antagonistas de Receptores de Angiotensina/efeitos adversos , Inibidores da Enzima Conversora de Angiotensina/efeitos adversos , Compostos de Bifenilo/efeitos adversos , Doenças Cardiovasculares/mortalidade , Método Duplo-Cego , Combinação de Medicamentos , Feminino , Hospitalização/estatística & dados numéricos , Humanos , Hipotensão/induzido quimicamente , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/complicações , Infarto do Miocárdio/mortalidade , Modelos de Riscos Proporcionais , Ramipril/efeitos adversos , Volume Sistólico , Valsartana/efeitos adversos , Disfunção Ventricular Esquerda/etiologiaRESUMO
BACKGROUND: In patients who survive an acute myocardial infarction (AMI), angiotensin-converting enzyme inhibitors decrease the risk of subsequent major cardiovascular events. Whether angiotensin-receptor blockade and neprilysin inhibition with sacubitril/valsartan reduce major coronary events more effectively than angiotensin-converting enzyme inhibitors in high-risk patients with recent AMI remains unknown. We aimed to compare the effects of sacubitril/valsartan on coronary outcomes in patients with AMI. METHODS: We conducted a prespecified analysis of the PARADISE-MI trial (Prospective ARNI vs ACE Inhibitors Trial to Determine Superiority in Reducing Heart Failure Events After MI), which compared sacubitril/valsartan (97/103 mg twice daily) with ramipril (5 mg twice daily) for reducing heart failure events after myocardial infarction in 5661 patients with AMI complicated by left ventricular systolic dysfunction, pulmonary congestion, or both. In the present analysis, the prespecified composite coronary outcome was the first occurrence of death from coronary heart disease, nonfatal myocardial infarction, hospitalization for angina, or postrandomization coronary revascularization. RESULTS: Patients were randomly assigned at a median of 4.4 [3.0-5.8] days after index AMI (ST-segment-elevation myocardial infarction 76%, non-ST-segment-elevation myocardial infarction 24%), by which time 89% of patients had undergone coronary reperfusion. Compared with ramipril, sacubitril/valsartan decreased the risk of coronary outcomes (hazard ratio, 0.86 [95% CI, 0.74-0.99], P=0.04) over a median follow-up of 22 months. Rates of the components of the composite outcomes were lower in patients on sacubitril/valsartan but were not individually significantly different. CONCLUSIONS: In survivors of an AMI with left ventricular systolic dysfunction and pulmonary congestion, sacubitril/valsartan-compared with ramipril-reduced the risk of a prespecified major coronary composite outcome. Dedicated studies are necessary to confirm this finding and elucidate its mechanism. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT02924727.
Assuntos
Insuficiência Cardíaca , Infarto do Miocárdio , Disfunção Ventricular Esquerda , Humanos , Aminobutiratos/uso terapêutico , Antagonistas de Receptores de Angiotensina/uso terapêutico , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Angiotensinas , Compostos de Bifenilo , Insuficiência Cardíaca/complicações , Insuficiência Cardíaca/diagnóstico , Insuficiência Cardíaca/tratamento farmacológico , Infarto do Miocárdio/tratamento farmacológico , Neprilisina/antagonistas & inibidores , Estudos Prospectivos , Ramipril/uso terapêutico , Receptores de Angiotensina , Volume Sistólico , Tetrazóis/uso terapêutico , Valsartana/uso terapêutico , Disfunção Ventricular Esquerda/complicaçõesRESUMO
BACKGROUND: Prior clinical trials have investigated intravenous iron in patients with heart failure (HF) and iron deficiency, but the safety and efficacy of this therapy remains unclear. METHODS: We report the baseline demographics and clinical characteristics of patients enrolled in the HEART-FID study and compare HEART-FID participants with patients within other contemporary clinical trials of patients with HF with reduced ejection fraction (HFrEF), including other intravenous iron trials. RESULTS: In the 3,065 participants randomized in HEART-FID, median (IQR) age was 69.7 (62.0-76.5) years, 1,037 (33.8%) were female, 322 (10.5%) were Black, median ejection fraction was 32% (25%-37%), 1,837 (60.0%) had ischemic etiology, and baseline median NT-proBNP was 1,462 (721-2,966) pg/mL. Median baseline hemoglobin was 12.6 (11.6-13.6) g/dL, and median 6-minute walk test distance was 272 (196-350) m, similar to prior intravenous iron HFrEF trials. Common comorbidities included atrial fibrillation/flutter (43.7%), and type 2 diabetes (45.2%). Compared with several recent HFrEF trials, patients enrolled in HEART-FID had similar baseline demographics and clinical characteristics, though a greater proportion of women and Black participants were recruited in HEART-FID. In HEART-FID, HFrEF therapy included a beta-blocker in 92.5%, angiotensin-converting enzyme inhibitor/angiotensin receptor blocker/angiotensin receptor-neprilysin inhibitors (ARNI) in 86.1% (with 29.7% ARNI), and a mineralocorticoid antagonist (MRA) in 55.6%. CONCLUSIONS: Patients enrolled in HEART-FID were similar to those enrolled in other contemporary HFrEF trials and registries, including trials of intravenous iron in HFrEF. However, the HEART-FID cohort is substantially larger and more racially diverse than prior trials of intravenous iron in HFrEF. TRIAL REGISTRATION: ClinicalTrials.gov (NCT03037931).
Assuntos
Diabetes Mellitus Tipo 2 , Insuficiência Cardíaca , Deficiências de Ferro , Humanos , Feminino , Idoso , Masculino , Insuficiência Cardíaca/complicações , Insuficiência Cardíaca/tratamento farmacológico , Diabetes Mellitus Tipo 2/tratamento farmacológico , Volume Sistólico , Ferro , Antagonistas de Receptores de Angiotensina/uso terapêuticoRESUMO
BACKGROUND: Dyspnea, the cardinal manifestation of chronic heart failure (CHF), may reflect both pulmonary oedema and pulmonary remodeling resulting in tissue stiffening. Emerging evidence suggests that predominance of distinct phenotypes of alveolar and recruited macrophages, designated M1 and M2, may regulate the course of inflammatory tissue repair and remodeling in the lung. METHODS: In a CHF rat model, we found fibrotic reinforcement of the extracellular matrix with an increase in monocyte chemotactic protein (MCP)-1/CCL2 in bronchoalveolar lavage (BAL), corresponding to a 3-fold increase in recruited macrophages. In this clinical cross sectional study, we aimed to examine potential mediators of leukocyte activation and lung infiltration in parallel BAL and blood from CHF patients compared to non-CHF controls. RESULTS: Mini-BAL and peripheral blood samples were obtained from hospitalized CHF, acute decompensated CHF and non-CHF patients. CHF patients and decompensated CHF patients demonstrated increases from non-CHF patients in BAL MCP-1, as well as the M2 macrophage cytokines interleukin-10 and transforming growth factor-ß. BAL and plasma MCP-1 were significantly correlated; however, MCP-1 was 20-fold higher in epithelial lining fluid in BAL, indicative of an alveolar chemotactic gradient. An increase in transglutaminase 2 positive M2 macrophages in parallel with a decrease in the MCP-1 receptor, CC chemokine receptor 2 (CCR2), was apparent in BAL cells of CHF patients compared to non-CHF. CONCLUSION: These data suggest a pathway of MCP-1 mediated M2 macrophage prevalence in the lungs of CHF patients which may contribute to pulmonary fibrotic remodeling and consequent increased severity of dyspnea.
Assuntos
Insuficiência Cardíaca , Fibrose Pulmonar , Ratos , Animais , Receptores CCR2/metabolismo , Monócitos/metabolismo , Fibrose Pulmonar/metabolismo , Estudos Transversais , Quimiocina CCL2/metabolismo , Pulmão/metabolismo , Proteínas Quimioatraentes de Monócitos/metabolismo , Insuficiência Cardíaca/patologia , DispneiaRESUMO
BACKGROUND: Recent clinical trials have demonstrated that sodium-glucose cotransporter 2 inhibitors (SGLT2i), which were previously only indicated in treatment of type 2 diabetes mellitus (T2DM), can markedly reduce heart failure hospitalisation (HFH), with less striking potential reductions in acute coronary syndromes and cardiac arrhythmias. To evaluate the impact of SGLT2i on cardiovascular outcomes in real-world practice, we performed a retrospective cohort analysis on South Australian (SA) data. METHODS: A total of 842 individuals with T2DM receiving SGLT2i were identified from SA public hospitals between 2011 and 2019. Episodes of care were temporally matched with those of 3,128 individuals with T2DM not receiving SGLT2i (control). Baseline characteristics were adjusted using inverse probability treatment weighting. The incidence of cardiovascular events at 12 and 24 months was evaluated using coded (International Classification of Diseases, Tenth Revision, Australian Modification [ICD-10-AM]) data. RESULTS: The primary outcome of HFH was lower with SGLT2i use at 12 months (adjusted hazard ratio [HRadj] 0.44; 95% confidence interval [CI] 0.29-0.68; p<0.001) and 24 months. There were also lower hospitalisations due to acute myocardial infarction (HRadj 0.42; 95% CI 0.21-0.85; p=0.015) and atrial or ventricular arrhythmias (HRadj 0.29; 95% CI 0.14-0.59; p=0.001), with no difference observed in hospitalisation due to ischaemic cerebrovascular events. There was no difference in all-cause mortality at 12 months but interestingly a higher rate at 24 months (HRadj 2.08; 95% CI 1.59-2.72; p<0.001). Despite this, similar reductions in cardiovascular outcomes were observed at 24 months. CONCLUSION: Use of SGLT2i in patients with T2DM in SA was associated with reductions in cardiovascular events even before their recent Pharmaceutical Benefits Scheme (PBS) listing for heart failure. Furthermore, this analysis supports that SGLT2i play a role not only in HFH reduction but also in reducing coronary and tachyarrhythmic events. This real-world evidence supports the use of SGLT2i as broadly protective cardiovascular drugs.
Assuntos
Diabetes Mellitus Tipo 2 , Insuficiência Cardíaca , Humanos , Austrália do Sul/epidemiologia , Austrália , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/epidemiologia , Estudos Retrospectivos , Insuficiência Cardíaca/tratamento farmacológico , Insuficiência Cardíaca/epidemiologia , Átrios do Coração , Glucose , SódioRESUMO
INTRODUCTION: Experienced echocardiographers can quickly glean diagnostic information from limited echocardiographic views. The use of limited cardiac ultrasound, particularly as a screening tool, is increasing. During the COVID-19 pandemic, limited cardiac ultrasound has the major advantage of reducing exposure time between sonographer and patient. The sensitivity and negative predictive value of a "screening" echocardiogram with highly limited views is uncertain. AIM/METHOD: We examined the accuracy of limited echocardiography in 203 consecutive, de novo studies. We used six images: parasternal long axis, with colour Doppler over the mitral valve, and aortic valve, and apical four-chamber with colour Doppler over the mitral valve, and tricuspid valve. We compared the interpretation of 12 subjects with the final echocardiogram report, (gold standard). The subjects comprised four experienced echocardiography-specialised cardiologists, four experienced cardiologists with non-imaging subspecialty interests, and four senior cardiac sonographers. Studies were graded as: (1) normal or (2) needs full study (due to inadequate images or abnormality detected). Sensitivity, specificity, negative predictive value, positive predictive value and accuracy are reported. RESULTS: Forty-one per cent (41%) of studies were normal by the gold standard report. Overall, a screening echocardiogram had a sensitivity of 71.2%, specificity of 57.1% to detect an abnormal echocardiogram, negative predictive value 58.4%, positive predictive value of 70.2%, and accuracy of 65.4%. When inadequate images were excluded, overall accuracy was nearly identical at 64.6%. The overall accuracy between the three groups of interpreters was similar: 66.5% (95% CI 63.1-69.7) for echocardiography-specialised cardiologists, 65.3% (95% CI 61.9-68.5) for non-echocardiography specialised cardiologists, and 64.4% (95% CI 61.0-67.7) for sonographers. These groups are all highly experienced practitioners. There was no difference in sensitivity or specificity comparing echocardiography-specialised cardiologists with cardiologists of other subspecialty experience. Comparing cardiologists to sonographers, cardiologists had lower sensitivity (echocardiography specialists 67.6%, 95% CI 63.2-71.8, non-echocardiography specialists 62.0%, 95% CI 57.4-66.4) compared to sonographers (84.0% [95% CI 80.4-87.2, p<0.05]), but cardiologists had higher specificities (64.9% [95% CI 59.5-70.0] for the echocardiography specialists, and 69.9% [95% CI 64.7-74.8] for non echocardiography specialists), compared to 36.6% (95% CI 31.4-42.0, p<0.05) for the sonographer group. When looking at only the studies considered to be interpretable, cardiologists had higher positive predictive value (echocardiography specialists 73.7%, 95% CI 69.0-78.1, non echocardiography specialists 74.1%, 95% CI 68.8-79.9), as compared to sonographers (64.3%, 95% CI 59.8-68.5%). CONCLUSIONS: Limited cardiac ultrasound as a screening tool for a normal heart had a sensitivity of only 71%, when performed and interpreted by experienced personnel, raising questions regarding the safety of this practice. Caution is especially recommended in extrapolating its use to non-specialised settings.
Assuntos
COVID-19 , Pandemias , Ecocardiografia/métodos , Humanos , Programas de Rastreamento , Valva MitralRESUMO
OBJECTIVE: Frailty is common in the aortic stenosis (AS) population and impacts outcomes after both transcatheter and surgical aortic valve replacement (TAVR and sAVR, respectively). Frailty can significantly impact the decision regarding the suitability of a patient for aortic valve intervention, with frail patients often excluded. Since many frailty tools use indicators which may be influenced by AS itself, some of which are subjectively symptom driven, we sought to determine the impact of intervention on frailty scores. METHODS: A prospective, observational cohort study included patients being assessed for aortic valve (AV) intervention with either TAVR or sAVR due to severe aortic stenosis. Patients were assessed for symptoms at baseline, and 1- and 6-months post intervention subjectively, using the New York Heart Association (NYHA) class and the Kansas City Cardiomyopathy Questionnaire (KCCQ), and objectively, using a 6-minute walk test (6MWT). These were compared with frailty at baseline and final review using the Fried Frailty Scale (FFS). RESULTS AND CONCLUSIONS: Sixty-six (66) patients completed pre- and post-intervention reviews. The mean FFS score was significantly lower, indicating less frailty, at 6 months relative to pre procedure (1.18 vs 1.73, p=0.002). This correlated with the change in symptoms (p<0.001). Between intervention groups, the final mean FFS of both groups decreased significantly, with TAVR to 1.33 (p=0.030) and sAVR to 0.8 (p=0.015). There was no difference in the degree of improvement between interventions (p=0.517). Aortic valve intervention improves frailty scores in both TAVR and sAVR treated patients.
Assuntos
Estenose da Valva Aórtica , Fragilidade , Implante de Prótese de Valva Cardíaca , Substituição da Valva Aórtica Transcateter , Valva Aórtica/cirurgia , Estenose da Valva Aórtica/diagnóstico , Estenose da Valva Aórtica/cirurgia , Fragilidade/diagnóstico , Implante de Prótese de Valva Cardíaca/métodos , Humanos , Estudos Prospectivos , Fatores de Risco , Substituição da Valva Aórtica Transcateter/métodos , Resultado do TratamentoRESUMO
BACKGROUND: In pulmonary arterial hypertension (PAH), progressive right ventricular (RV) dysfunction is believed to be largely secondary to RV ischaemia. A recent pilot study has demonstrated the feasibility of Oxygen-sensitive (OS) cardiovascular magnetic resonance (CMR) to detect in-vivo RV myocardial oxygenation. The aims of the present study therefore, were to assess the prevalence of RV myocardial ischaemia and relationship with RV myocardial interstitial changes in PAH patients with non-obstructive coronaries, and corelate with functional and haemodynamic parameters. METHODS: We prospectively recruited 42 patients with right heart catheter (RHC) proven PAH and 11 healthy age matched controls. The CMR examination involved standard functional imaging, OS-CMR imaging and native T1 mapping. An ΔOS-CMR signal intensity (SI) index (stress/rest signal intensity) was acquired at RV anterior, RV free-wall and RV inferior segments. T1 maps were acquired using Shortened Modified Look-Locker Inversion recovery (ShMOLLI) at the inferior RV segment. RESULTS: The inferior RV ΔOS-CMR SI index was significantly lower in PAH patients compared with healthy controls (9.5 (- 7.4-42.8) vs 12.5 (9-24.6)%, p = 0.02). The inferior RV ΔOS-CMR SI had a significant correlation to RV inferior wall thickness (r = - 0.7, p < 0.001) and RHC mean pulmonary artery pressure (mPAP) (r = - 0.4, p = 0.02). Compared to healthy controls, patients with PAH had higher native T1 in the inferior RV wall: 1303 (1107-1612) vs 1232 (1159-1288)ms, p = 0.049. In addition, there was a significant difference in the inferior RV T1 values between the idiopathic PAH and systemic sclerosis associated PAH patients: 1242 (1107-1612) vs 1386 (1219-1552)ms, p = 0.007. CONCLUSION: Blunted OS-CMR SI suggests the presence of in-vivo microvascular RV dysfunction in PAH patients. The native T1 in the inferior RV segments is significantly increased in the PAH patients, particularly among the systemic sclerosis associated PAH group.
Assuntos
Isquemia Miocárdica/etiologia , Miocárdio/metabolismo , Oxigênio/metabolismo , Hipertensão Arterial Pulmonar/complicações , Disfunção Ventricular Direita/etiologia , Função Ventricular Direita , Idoso , Estudos de Casos e Controles , Circulação Coronária , Feminino , Humanos , Imagem Cinética por Ressonância Magnética , Masculino , Microcirculação , Pessoa de Meia-Idade , Isquemia Miocárdica/diagnóstico por imagem , Isquemia Miocárdica/metabolismo , Isquemia Miocárdica/fisiopatologia , Estudos Prospectivos , Hipertensão Arterial Pulmonar/diagnóstico por imagem , Hipertensão Arterial Pulmonar/metabolismo , Hipertensão Arterial Pulmonar/fisiopatologia , Austrália do Sul , Disfunção Ventricular Direita/diagnóstico por imagem , Disfunção Ventricular Direita/metabolismo , Disfunção Ventricular Direita/fisiopatologia , Função Ventricular EsquerdaRESUMO
BACKGROUND: Hydrostatic lung injury followed by pulmonary remodelling variably complicates cardiogenic acute pulmonary oedema (APO). Pulmonary remodelling may be regulated by the balance between distinct phenotypes of pulmonary macrophages; activated/inflammatory (M1), and reparative/anti-inflammatory (M2), derived from circulating monocyte populations. The aim of this study was to identify biomarkers in peripheral blood that are consistent with hydrostatic lung injury and pulmonary remodelling in APO and which follow the variable clinical course. METHODS: To examine peripheral markers of lung inflammation, resolution and remodelling, 18 patients, admitted to the intensive care unit (ICU) with a clinical diagnosis of APO, were enrolled. Admission, 12- and 24-hour post-admission bloods were assayed for cytokines by ELISA (R&D Systems, Minneapolis, MN, USA) and leukocyte surface markers by flow cytometry. RESULTS: Admission PaO2 to FiO2 ratio was positively correlated with Mon 2 (intermediate) monocyte prevalence, through increasing ratio of CD16+ monocytes to CD11b+ and CD40+ monocytes, and negatively correlated with Mon 1 (classical) monocyte prevalence, through decreasing ratio of CD16+ monocytes to CD62L+. Secondary cohort analysis compared 10 APO patients with established chronic heart failure (CHF) to eight without CHF. An increase in monocyte chemotactic peptide (MCP)-1, monocyte prevalence, and CD16-CD62L+ monocytes with CHF, all characteristic of monocyte activation to a Mon 1 phenotype, were found in the CHF APO patients. CONCLUSIONS: Increased systemic monocyte prevalence and expression of cell surface markers suggest a Mon 1 profile in CHF patients during episodes of APO. Future studies should define the role of systemic monocyte prevalence and activation in decompensated CHF.
Assuntos
Citocinas/sangue , Monócitos/metabolismo , Edema Pulmonar/sangue , Doença Aguda , Idoso , Biomarcadores/sangue , Estudos de Casos e Controles , Feminino , Citometria de Fluxo , Humanos , MasculinoRESUMO
BACKGROUND: Nutraceuticals are pharmacologically active substances extracted from vegetable or animal food and administered to produce health benefits. We recently reviewed the current evidence for nutraceuticals in patients diagnosed with heart failure as part of the writing of the Australian Guidelines for the prevention, diagnosis, and management of heart failure. METHODS: A systematic search for studies that compared nutraceuticals to standard care in adult patients with heart failure was performed. Studies were included if >50 patients were enrolled, with ≥6 months follow-up. If no studies met criteria then studies <50 patients and <6 months follow-up were included. The primary outcomes included mortality/survival, hospitalization, quality of life, and/or exercise tolerance. Iron was not included in this review as its role in heart failure is already well established. RESULTS: Forty studies met the inclusion criteria. The strongest evidence came from studies of polyunsaturated fatty acids, which modestly decreased mortality and cardiovascular hospitalizations in patients with mostly New York Heart Association class II and III heart failure across a range of left ventricular ejection fraction. Coenzyme Q10 may decrease mortality and hospitalization, but definite conclusions cannot be drawn. Studies that examined nitrate-rich beetroot juice, micronutrient supplementation, hawthorn extract, magnesium, thiamine, vitamin E, vitamin D, L-arginine, L-carnosine, and L-carnitine were too small or underpowered to properly appraise clinical outcomes. CONCLUSION: Only one nutraceutical, omega-3 polyunsaturated fatty acid, received a positive recommendation in the Australian heart failure guidelines. Although occasionally showing some promise, all other nutraceuticals are inadequately studied to allow any conclusion on efficacy. Clinicians should favor other treatments that have been clearly shown to decrease mortality.
Assuntos
Suplementos Nutricionais , Ácidos Graxos Ômega-3/administração & dosagem , Insuficiência Cardíaca/dietoterapia , Insuficiência Cardíaca/diagnóstico , Ensaios Clínicos Controlados Aleatórios como Assunto/métodos , HumanosRESUMO
BACKGROUND: Acute decompensated heart failure (ADHF) carries a high event rate following discharge. The complex interplay between age, frailty and decongestion may lend itself to a functional test. METHODS: In the doorbell test the patient simulates answering the doorbell. They are timed rising from a recumbent position, bending over twice and walking 10 metres, this time is added to the change in respiratory rate. We aimed to determine if the doorbell test was associated with post ADHF events (death or readmission). The test was performed at hospital discharge, with follow up at 30-days and 1-year. RESULTS: In 74 patients at 30-days there was a 14% event rate. At 1-year there were 40 (54%) events (9 deaths and 31 readmissions, 28 were cardiovascular of which 14 were [heart failure] HF). Amongst those who had an event at 30-days only doorbell test scores were different (58 [36,72] vs 32 [26,53] p < 0.05). One-year (1-year) events were associated with doorbell test scores (47 [29,62] vs 30 [26,42] p < 0.05), body weight (78 kg [68,94] vs 95 [76,105] (p < 0.05), creatinine (134 mmol/L [114, 173] vs 99 [82, 133] p < 0.01) and age (76 years [61,86] vs 67 [53, 73] p < 0.01). Heart failure readmissions were associated with doorbell test scores (56 [46,68] vs 30 [26,47] p < 0.001). Death was associated with body weight (74 kg [69,81] vs 88 [72,101] p < 0.05) and age (83 years [78,86] vs 69 [55,77] p < 0.01). After age stratification, the hazard ratio for heart failure readmission associated with a high doorbell test score was 11.08 (95%C.I. 2.01-61.17 p = 0.006), while the hazard ratio for 1-year cardiovascular readmission was 4.62 (95%C.I. 1.71-12.51 p = 0.003). There was no association with 1-year mortality. CONCLUSION: The doorbell test represents a novel test of multiple domains of the ADHF pre-discharge state and demonstrates an association with 30-day and 1-year rehospitalisation.
Assuntos
Teste de Esforço/métodos , Fragilidade/diagnóstico , Insuficiência Cardíaca/diagnóstico , Caminhada/fisiologia , Doença Aguda , Idoso , Feminino , Fragilidade/complicações , Fragilidade/fisiopatologia , Insuficiência Cardíaca/complicações , Insuficiência Cardíaca/fisiopatologia , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de RiscoAssuntos
Aminobutiratos/uso terapêutico , Anti-Hipertensivos/uso terapêutico , Compostos de Bifenilo/uso terapêutico , Insuficiência Cardíaca/tratamento farmacológico , Ramipril/uso terapêutico , Valsartana/uso terapêutico , Aminobutiratos/farmacologia , Anti-Hipertensivos/farmacologia , Compostos de Bifenilo/farmacologia , Combinação de Medicamentos , Humanos , Ramipril/farmacologia , Valsartana/farmacologiaRESUMO
INTRODUCTION: Heart failure (HF) is a clinical syndrome that is secondary to an abnormality of cardiac structure or function. These clinical practice guidelines focus on the diagnosis and management of HF with recommendations that have been graded on the strength of evidence and the likely absolute benefit versus harm. Additional considerations are presented as practice points. Main recommendations: Blood pressure and lipid lowering decrease the risk of developing HF. Sodium-glucose cotransporter 2 inhibitors decrease the risk of HF hospitalisation in patients with type 2 diabetes and cardiovascular disease. An echocardiogram is recommended if HF is suspected or newly diagnosed. If an echocardiogram cannot be arranged in a timely fashion, measurement of plasma B-type natriuretic peptides improves diagnostic accuracy. Angiotensin-converting enzyme inhibitors, ß-blockers and mineralocorticoid receptor antagonists improve outcomes in patients with HF associated with a reduced left ventricular ejection fraction. Additional treatment options in selected patients with persistent HF associated with reduced left ventricular ejection fraction include switching the angiotensin-converting enzyme inhibitor to an angiotensin receptor neprilysin inhibitor; ivabradine; implantable cardioverter defibrillators; cardiac resynchronisation therapy; and atrial fibrillation ablation. Multidisciplinary HF disease management facilitates the implementation of evidence-based HF therapies. Clinicians should also consider models of care that optimise medication titration (eg, nurse-led titration). Changes in management as a result of the guideline: These guidelines have been designed to facilitate the systematic integration of recommendations into HF care. This should include ongoing audit and feedback systems integrated into work practices in order to improve the quality of care and outcomes of patients with HF.
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Insuficiência Cardíaca , Austrália , Insuficiência Cardíaca/diagnóstico , Insuficiência Cardíaca/prevenção & controle , Insuficiência Cardíaca/terapia , HumanosRESUMO
BACKGROUND: Paravalvular aortic regurgitation (PAR) following transcatheter aortic valve implantation (TAVI) is well acknowledged. Despite improvements, echocardiographic measurement of PAR largely remains qualitative. Cardiovascular magnetic resonance (CMR) directly quantifies AR with accuracy and reproducibility. We compared CMR and transthoracic echocardiography (TTE) analysis of pre-operative and post-operative aortic regurgitation in patients undergoing both TAVI and surgical aortic valve replacement (AVR). METHODS: Eighty-seven patients with severe aortic stenosis undergoing TAVI (56 patients) or AVR were recruited. CMR (1.5 T) and transthoracic echocardiography (TTE) were carried out pre-operatively and a median of 6 days post-operatively. The CMR protocol included regurgitant aortic flows using through-plane phase-contrast velocity. None/trivial, mild, moderate and severe AR by CMR was defined as ≤8%, 9-20%, 21-39%, >40% regurgitant fractions respectively. RESULTS: Pre- and post-operative left ventricular ejection fraction (LVEF) was similar. Post-procedure aortic regurgitant fraction using CMR was higher in the TAVI group (TAVI 16 ± 13% vs. AVR 4 ± 4%, p < 0.01). Comparing CMR to TTE, 27 of 56 (48%) TAVI patients had PAR which was at least one grade more severe on CMR than TTE (Z = -4.56, p <0.001). Sensitivity analysis confirmed the difference in PAR grade between TTE and CMR in the TAVI group (Z = -4.49, p < 0.001). CONCLUSION: When compared to CMR based quantitative analysis, TTE underestimated the degree of paravalvular aortic regurgitation. This underestimation may in part explain the findings of increased mortality associated with mild or greater AR by TTE in the PARTNER trial. Paravalvular aortic regurgitation post TAVI assessed as mild by TTE may in fact be more severe.
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Insuficiência da Valva Aórtica/diagnóstico , Estenose da Valva Aórtica/terapia , Valva Aórtica , Cateterismo Cardíaco/efeitos adversos , Implante de Prótese de Valva Cardíaca/efeitos adversos , Hemodinâmica , Imageamento por Ressonância Magnética , Idoso , Idoso de 80 Anos ou mais , Valva Aórtica/diagnóstico por imagem , Valva Aórtica/fisiopatologia , Insuficiência da Valva Aórtica/diagnóstico por imagem , Insuficiência da Valva Aórtica/etiologia , Insuficiência da Valva Aórtica/fisiopatologia , Estenose da Valva Aórtica/diagnóstico , Estenose da Valva Aórtica/fisiopatologia , Feminino , Implante de Prótese de Valva Cardíaca/métodos , Humanos , Masculino , Valor Preditivo dos Testes , Reprodutibilidade dos Testes , Índice de Gravidade de Doença , Volume Sistólico , Fatores de Tempo , Resultado do Tratamento , Ultrassonografia , Função Ventricular EsquerdaRESUMO
BACKGROUND: Myocardial ischemia is a major cause of death in chronic kidney disease (CKD) patients, which can be caused by either epicardial or microvascular coronary artery disease (CAD). Although renal transplantation improves survival, cardiovascular disease remains a major cause of mortality in post renal transplant recipients, including those with no significant epicardial CAD pre-transplant. We aim to utilize stress cardiovascular magnetic resonance (CMR) and MR coronary angiography (MRCA) to assess silent myocardial ischemia and epicardial CAD in renal transplant recipients. METHODS: Forty-five subjects: twenty renal transplant (RT) with no known CAD, fifteen liver transplant (LT) controls without prior CKD and no known CAD, and ten hypertensive (HT) controls underwent stress perfusion CMR and MRCA. RESULTS: A total of 1308 myocardial segments (576 of RT, 468 of LT, and 264 of HT) were compared using mixed linear modeling. Left ventricular mass index, septal diameter and presence of diabetes mellitus were similar between the groups. The mean transmural MPRI was significantly lower in the RT and LT groups compared to HT controls (1.19 ± 0.50 in RT versus 1.23 ± 0.36 in LT versus 2.04 ± 0.32 in HT controls, p < 0.0001), in the subepicardium (1.33 ± 0.57 in RT versus 1.30 ± 0.33 in LT versus 2.01 ± 0.30 in HT controls, p < 0.001), and in the subendocardium (1.19 ± 0.54 in RT versus 1.11 ± 0.31 in LT versus 1.85 ± 0.34 in HT controls, p < 0.0001). Seven (35%) RT and five (33%) LT had significant epicardial CAD compared to none in HT controls, p = 0.12. One RT and one LT had LGE suggesting sub-endocardial infarction. CONCLUSIONS: RT recipients have impaired myocardial perfusion independent of LVH or diabetes mellitus. The impaired myocardial perfusion in RT is similar to LT without prior renal disease, thus unlikely related to previous CKD. It is not fully explained by the presence of significant epicardial CAD, and therefore most likely represents microvascular CAD.
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Doença da Artéria Coronariana/diagnóstico , Circulação Coronária , Transplante de Rim , Transplante de Fígado , Imagem Cinética por Ressonância Magnética , Microcirculação , Imagem de Perfusão do Miocárdio/métodos , Adulto , Idoso , Doenças Assintomáticas , Estudos de Casos e Controles , Angiografia Coronária , Doença da Artéria Coronariana/diagnóstico por imagem , Doença da Artéria Coronariana/etiologia , Doença da Artéria Coronariana/fisiopatologia , Feminino , Humanos , Transplante de Rim/efeitos adversos , Modelos Lineares , Transplante de Fígado/efeitos adversos , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Valor Preditivo dos Testes , Fatores de Risco , Resultado do TratamentoRESUMO
BACKGROUND: Chronic heart failure (CHF) following coronary artery ligation and myocardial infarction in the rat leads to a homeostatic reduction in surface tension with associated alveolar type II cell hyperplasia and increased surfactant content, which functionally compensates for pulmonary collagen deposition and increased tissue stiffness. To differentiate the effects on lung remodelling of the sudden rise in pulmonary microvascular pressure (Pmv) with myocardial infarction from its consequent chronic elevation, we examined a hypertensive model of CHF. METHODS: Cardiopulmonary outcomes due to chronic pulmonary capillary hypertension were assessed at six and 15 weeks following abdominal aortic banding (AAB) in the rat. RESULTS: At six weeks post-surgery, despite significantly elevated left ventricular end-diastolic pressure, myocardial hypertrophy and increased left ventricular internal circumference in AAB rats compared with sham operated controls (p≤0.003), lung weights and tissue composition remained unchanged, and lung compliance was normal. At 15 weeks post-surgery increased lung oedema was evident in AAB rats (p=0.002) without decreased lung compliance or evidence of tissue remodelling. CONCLUSION: Despite chronically elevated Pmv, comparable to that resulting from past myocardial infarction (LVEDP>19mmHg), there is no evidence of pulmonary remodelling in the AAB model of CHF.
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Pressão Sanguínea , Capilares/fisiopatologia , Insuficiência Cardíaca/fisiopatologia , Hipertensão/fisiopatologia , Infarto do Miocárdio/fisiopatologia , Animais , Doença Crônica , Modelos Animais de Doenças , Insuficiência Cardíaca/etiologia , Masculino , Infarto do Miocárdio/complicações , Ratos , Ratos Sprague-DawleyRESUMO
AIMS: Ferric carboxymaltose (FCM) is guideline-recommended for iron deficiency (ID) in heart failure with reduced ejection fraction (HFrEF). Despite a well-established safety profile, the magnitude and clinical significance of FCM-induced hypophosphataemia in HFrEF remains unclear. This pre-specified substudy of HEART-FID evaluated serum phosphate, 1,25-dihydroxyvitamin D, and plasma parathyroid hormone (PTH) subsequent to FCM. METHODS AND RESULTS: HEART-FID was a randomized, double-blind, placebo-controlled trial of ambulatory patients with HFrEF and ID randomized to FCM versus placebo. This substudy assessed mean change from baseline across eight visits over 6 months for the following endpoints: serum phosphate, 25-hydroxyvitamin D, 1,25-dihydroxyvitamin D, and PTH, in addition to the clinical severity of potential hypophosphataemia. Overall, 133 patients (n = 62 FCM, n = 71 placebo) were prospectively enrolled. Mean age was 68 ± 11 years, 55 (41.4%) were women, and 29 (21.8%) had chronic kidney disease. Phosphate levels decreased in 34 (57.6%) patients in the FCM group compared with 7 (10.3%) in the placebo group. Mean change in phosphate levels reached a nadir at day 21 (-0.36 ± 0.27 mmol/L) subsequent to FCM infusion with 28 (51%) having moderate-to-severe hypophosphataemia. Reductions in 1,25-dihydroxyvitamin D were also observed, whilst PTH increased. These biochemical changes returned to baseline levels by day 91. Serum levels of 25-hydroxyvitamin D remained stable throughout the study. No serious adverse events associated with hypophosphataemia were reported. CONCLUSIONS: Transient moderate-to-severe hypophosphataemia was frequent subsequent to FCM infusion, accompanied by 1,25-dihydroxyvitamin D decrease and PTH increase. Serum levels of 25-hydroxyvitamin D remained stable. No evidence of symptomatic hypophosphataemia was reported, collectively indicating FCM-related hypophosphataemia to be clinically benign and transient in HFrEF.
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BACKGROUND: Clinical trials in heart failure (HF) traditionally use time-to-event analyses focusing on death and hospitalization for HF. These time-to-first event analyses may have more limited abilities to assess the probability of benefiting from a therapy, especially if that benefit manifests as improved functional status rather than reduced risk of death or HF hospitalization. Hierarchical end points including clinical outcomes and patient status measures allow for ranked evaluation of outcomes in 1 metric assessing whether patients randomized to intervention or control are more likely to derive an overall benefit while also allowing more patients to contribute to the primary outcome. METHODS: We review the rationale for using hierarchical end points in HF trials, provide examples of HF trials that used this type of end point, and discuss its use in the HEART-FID trial (Randomized Placebo-Controlled Trial of Ferric Carboxymaltose as Treatment for Heart Failure With Iron Deficiency), the largest HF trial to date implementing a hierarchical end point analysis for the primary outcome. RESULTS: Using a hierarchical end point as the primary outcome allows for the inclusion of different types of outcomes in 1 ranked end point, making it possible to more holistically assess the potential utility of a new therapy on patient well-being and outcomes. CONCLUSIONS: Hierarchical end points assess the potential utility of a new therapy on patient well-being and outcome more holistically than time-to-first event analysis. Trials that would not have been feasible due to decreasing rates of death and hospitalization in the HF population can use hierarchical end points to successfully power studies to identify promising HF therapies. The HEART-FID trial used hierarchical end points to better determine the role of intravenous ferric carboxymaltose in patients with HF. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03037931.
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Insuficiência Cardíaca , Maltose/análogos & derivados , Humanos , Insuficiência Cardíaca/diagnóstico , Insuficiência Cardíaca/tratamento farmacológico , Resultado do Tratamento , Compostos Férricos , Hospitalização , Volume Sistólico , Ensaios Clínicos Controlados Aleatórios como AssuntoRESUMO
Recently it has been demonstrated that high resolution transthoracic echocardiography (HRTTE) is able to detect differences in the wall thickness of the left anterior descending coronary artery (LAD) between patients with coronary artery disease (CAD) and normal volunteers. We sought to validate this technique, develop a normal range of values and demonstrate the test-retest variability of each measurement. Two hundred forty-two volunteer participants had a HRTTE study to measure their LAD wall thickness, luminal, and external diameters. Thirty of these subjects had these measurements taken on 3 separate occasions by 2 different echosonographers. All subjects were free of clinical CAD, hypertension, hyperlipidemia, and diabetes mellitus. The average anterior wall thickness was 1.1 ± 0.2 mm; posterior wall thickness was 1.1 ± 0.2 mm, luminal diameter 2.2 ± 0.6 mm, and external elastic membrane (EEM) diameter 4.5 ± 0.9 mm. The bias of the measurements within the same operator for LAD wall thickness, luminal diameter, and EEM was 0.042, -0.06, and -0.077 mm, respectively. The bias of the measurements between 2 different operators for LAD wall thickness, luminal diameter, and EEM was 0.082, -0.077, and -0.027 mm, respectively. In conclusion, HRTTE measurement of the LAD vessel is reproducible within and between operators in normal volunteers. This technique therefore warrants further study as a potential screening modality for subclinical coronary atherosclerosis.