RESUMO
Hypertrophic cardiomyopathy (HCM) is a heritable disease of heart muscle that increases the risk for heart failure, stroke, and sudden death, even in asymptomatic patients. With only 10-20% of affected people currently diagnosed, there is an unmet need for an effective screening tool outside of the clinical setting. Photoplethysmography uses a noninvasive optical sensor incorporated in commercial smart watches to detect blood volume changes at the skin surface. In this study, we obtained photoplethysmography recordings and echocardiograms from 19 HCM patients with left ventricular outflow tract obstruction (oHCM) and a control cohort of 64 healthy volunteers. Automated analysis showed a significant difference in oHCM patients for 38/42 morphometric pulse wave features, including measures of systolic ejection time, rate of rise during systole, and respiratory variation. We developed a machine learning classifier that achieved a C-statistic for oHCM detection of 0.99 (95% CI: 0.99-1.0). With further development, this approach could provide a noninvasive and widely available screening tool for obstructive HCM.
RESUMO
Background: Mavacamten, an orally administered, small-molecule modulator of cardiac myosin, targets underlying biomechanical abnormalities in obstructive hypertrophic cardiomyopathy (oHCM). Objective: To characterize the effect of mavacamten on left ventricular outflow tract (LVOT) gradient. Design: Open-label, nonrandomized, phase 2 trial. (ClinicalTrials.gov: NCT02842242). Setting: 5 academic centers. Participants: 21 symptomatic patients with oHCM. Intervention: Patients in cohort A received mavacamten, 10 to 20 mg/d, without background medications. Those in cohort B received mavacamten, 2 to 5 mg/d, with ß-blockers allowed. Measurements: The primary end point was change in postexercise LVOT gradient at 12 weeks. Secondary end points included changes in peak oxygen consumption (pVO2), resting and Valsalva LVOT gradients, left ventricular ejection fraction (LVEF), and numerical rating scale dyspnea score. Results: In cohort A, mavacamten reduced mean postexercise LVOT gradient from 103 mm Hg (SD, 50) at baseline to 19 mm Hg (SD, 13) at 12 weeks (mean change, -89.5 mm Hg [95% CI, -138.3 to -40.7 mm Hg]; P = 0.008). Resting LVEF was also reduced (mean change, -15% [CI, -23% to -6%]). Peak VO2 increased by a mean of 3.5 mL/kg/min (CI, 1.2 to 5.9 mL/kg/min). In cohort B, the mean postexercise LVOT gradient decreased from 86 mm Hg (SD, 43) to 64 mm Hg (SD, 26) (mean change, -25.0 mm Hg [CI, -47.1 to -3.0 mm Hg]; P = 0.020), and mean change in resting LVEF was -6% (CI, -10% to -1%). Peak VO2 increased by a mean of 1.7 mL/kg/min (SD, 2.3) (CI, 0.03 to 3.3 mL/kg/min). Dyspnea scores improved in both cohorts. Mavacamten was well tolerated, with mostly mild (80%), moderate (19%), and unrelated (79%) adverse events. The most common adverse events definitely or possibly related to mavacamten were decreased LVEF at higher plasma concentrations and atrial fibrillation. Limitation: Small size; open-label design. Conclusion: Mavacamten can reduce LVOT obstruction and improve exercise capacity and symptoms in patients with oHCM. Primary Funding Source: MyoKardia.
Assuntos
Benzilaminas/uso terapêutico , Cardiomiopatia Hipertrófica/tratamento farmacológico , Fármacos Cardiovasculares/uso terapêutico , Uracila/análogos & derivados , Função Ventricular Esquerda/efeitos dos fármacos , Administração Oral , Antagonistas Adrenérgicos beta/efeitos adversos , Antagonistas Adrenérgicos beta/uso terapêutico , Adulto , Idoso , Benzilaminas/efeitos adversos , Cardiomiopatia Hipertrófica/fisiopatologia , Fármacos Cardiovasculares/efeitos adversos , Relação Dose-Resposta a Droga , Quimioterapia Combinada , Tolerância ao Exercício , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Consumo de Oxigênio/efeitos dos fármacos , Estudos Prospectivos , Volume Sistólico/efeitos dos fármacos , Uracila/efeitos adversos , Uracila/uso terapêutico , Adulto JovemRESUMO
Heart Failure (HF) and chronic obstructive pulmonary disease (COPD) are morbid diseases that often coexist. In patients with coexisting disease, COPD is an independent risk factor for readmission and mortality. However, spirometry is often inaccurate in those with active heart failure. Therefore, we investigated the association between the presence of emphysema on computed tomography (CT) and readmission rates in smokers admitted with heart failure (HF). The cohort included a consecutive group of smokers discharged with HF from a tertiary center between January 1, 2014 and April 1, 2014 who also had a CT of the chest for dyspnea. The primary endpoint was any readmission for HF before April 1, 2016; secondary endpoints were 30-day readmission for HF, length of stay and all-cause mortality. Over the study period, there were 225 inpatient smokers with HF who had a concurrent chest CT (155 [69%] males, age 69±11 years, ejection fraction [EF] 46±18%, 107 [48%] LVEF of < 50%). Emphysema on CT was present in 103 (46%) and these were older, had a lower BMI, more pack-years, less diabetes and an increased afterload. During a follow-up of 2.1 years, there were 110 (49%) HF readmissions and 55 (24%) deaths. When separated by emphysema on CT, any readmission, 30-day readmission, length of stay and mortality were higher among HF patients with emphysema. In multivariable regression, emphysema by CT was associated with a two-fold higher (adjusted HR 2.11, 95% CI 1.41-3.15, p < 0.001) risk of readmission and a trend toward increased mortality (adjusted HR 1.70 95% CI 0.86-3.34, p = 0.12). In conclusion, emphysema by CT is a frequent finding in smokers hospitalized with HF and is associated with adverse outcomes in HF. This under recognized group of patients with both emphysema and heart failure may benefit from improved recognition and characterization of their co-morbid disease processes and optimization of therapies for their lung disease.
Assuntos
Insuficiência Cardíaca/mortalidade , Readmissão do Paciente , Doença Pulmonar Obstrutiva Crônica/mortalidade , Sistema de Registros , Fumar/mortalidade , Idoso , Idoso de 80 Anos ou mais , Intervalo Livre de Doença , Feminino , Insuficiência Cardíaca/complicações , Insuficiência Cardíaca/diagnóstico por imagem , Insuficiência Cardíaca/terapia , Humanos , Masculino , Pessoa de Meia-Idade , Doença Pulmonar Obstrutiva Crônica/complicações , Doença Pulmonar Obstrutiva Crônica/diagnóstico por imagem , Doença Pulmonar Obstrutiva Crônica/terapia , Estudos Retrospectivos , Fatores de Risco , Fumar/efeitos adversos , Fumar/terapia , Taxa de Sobrevida , Tomografia Computadorizada por Raios XRESUMO
After orthotopic heart transplantation (OHT), the allograft undergoes characteristic alterations in myocardial structure, including hypertrophy, increased ventricular stiffness, ischemia, and inflammation, all of which may decrease overall graft survival. Methods to quantify these phenotypes may clarify the pathophysiology of progressive graft dysfunction post-OHT. We performed cardiac magnetic resonance (CMR) with T1 mapping in 26 OHT recipients (mean age 47 ± 7 years, 30 % female, median follow-up post-OHT 6 months) and 30 age-matched healthy volunteers (mean age 50.5 ± 15 years; LVEF 63.5 ± 7 %). OHT recipients had a normal left ventricular ejection fraction (LVEF 65.3 ± 11 %) with higher LV mass relative to age-matched healthy volunteers (114 ± 27 vs. 85.8 ± 18 g; p < 0.001). There was no late gadolinium enhancement in either group. Both myocardial extracellular volume fraction (ECV) and intracellular lifetime of water (τic), a measure of cardiomyocyte hypertrophy, were higher in patients post-OHT (ECV: 0.39 ± 0.06 vs. 0.28 ± 0.03, p < 0.0001; τic: 0.12 ± 0.08 vs. 0.08 ± 0.03, p < 0.001). ECV was associated with LV mass (r = 0.74, p < 0.001). In follow-up, OHT recipients with normal biopsies by pathology (ISHLT grade 0R) in the first year post-OHT exhibited a lower ECV relative to patients with any rejection ≥2R (0.35 ± 0.02 for 0R vs. 0.45 ± 0, p < 0.001). Higher ECV but not LVEF was significantly associated with a reduced rejection-free survival. After OHT, markers of tissue remodeling by CMR (ECV and τic) are elevated and associated with myocardial hypertrophy. Interstitial myocardial remodeling (by ECV) is associated with cellular rejection. Further research on the impact of graft preservation and early immunosuppression on tissue-level remodeling of the allograft is necessary to delineate the clinical implications of these findings.
Assuntos
Cardiomegalia/diagnóstico por imagem , Transplante de Coração , Imagem Cinética por Ressonância Magnética , Miocárdio/patologia , Função Ventricular Esquerda , Remodelação Ventricular , Adulto , Idoso , Aloenxertos , Biópsia , Cardiomegalia/etiologia , Cardiomegalia/patologia , Cardiomegalia/fisiopatologia , Estudos de Casos e Controles , Estudos Transversais , Feminino , Fibrose , Rejeição de Enxerto/etiologia , Sobrevivência de Enxerto , Transplante de Coração/efeitos adversos , Humanos , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Valor Preditivo dos Testes , Fatores de Risco , Volume Sistólico , Fatores de Tempo , Resultado do TratamentoRESUMO
BACKGROUND: We aimed to develop a severity classification system of the main pulmonary artery diameter (mPA) and its ratio to the ascending aorta diameter (ratio PA) for the diagnosis and prognosis of pulmonary hypertension (PH) on computed tomography (CT) scans. METHODS: In 228 patients (136 with PH) undergoing right heart catheterization (RHC) and CT for dyspnea, we measured mPA and ratio PA. In a derivation cohort (n = 114), we determined cutpoints for a four-tier severity grading system that would maximize sensitivity and specificity, and validated it in a separate cohort (n = 114). Cutpoints for mPA were defined with ≤27 mm(F) and ≤29 mm(M) as the normal reference range; mild as >27 to <31 mm(F) and >29 to <31 mm(M); moderate≥31-34 mm; and severe>34 mm. Cutpoints for ratio PA were defined as normal ≤0.9; mild>0.9 to 1.0; moderate>1.0 to 1.1; and severe>1.1. RESULTS: Sensitivities for normal tier were 99% for mPA and 93% for ratio PA; while specificities for severe tier were 98% for mPA>34 mm and 100% for ratio PA>1.1. C-statistics for four-tier mPA and ratio PA were both 0.90 (derivation) and both 0.85 (validation). Severity of mPA and ratio PA corresponded to hemodynamics by RHC and echocardiography (both p < 0.001). Moderate-severe mPA values of ≥31 mm and ratio PA>1.1 had worse survival than normal values (all p ≤ 0.01). CONCLUSION: A CT-based four-tier severity classification system of PA diameter and its ratio to the aortic diameter has high accuracy for PH diagnosis with increased mortality in patients with moderate-severe severity grades. These results may support clinical utilization on chest and cardiac CT reports.
Assuntos
Aorta/diagnóstico por imagem , Aortografia/métodos , Angiografia por Tomografia Computadorizada/métodos , Hipertensão Pulmonar/diagnóstico por imagem , Artéria Pulmonar/diagnóstico por imagem , Interpretação de Imagem Radiográfica Assistida por Computador/métodos , Adulto , Idoso , Área Sob a Curva , Pressão Arterial , Estudos Transversais , Feminino , Humanos , Hipertensão Pulmonar/classificação , Hipertensão Pulmonar/fisiopatologia , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Prognóstico , Artéria Pulmonar/fisiopatologia , Curva ROC , Reprodutibilidade dos Testes , Índice de Gravidade de DoençaRESUMO
This pilot study used acoustic speech analysis to monitor patients with heart failure (HF), which is characterized by increased intracardiac filling pressures and peripheral edema. HF-related edema in the vocal folds and lungs is hypothesized to affect phonation and speech respiration. Acoustic measures of vocal perturbation and speech breathing characteristics were computed from sustained vowels and speech passages recorded daily from ten patients with HF undergoing inpatient diuretic treatment. After treatment, patients displayed a higher proportion of automatically identified creaky voice, increased fundamental frequency, and decreased cepstral peak prominence variation, suggesting that speech biomarkers can be early indicators of HF.
Assuntos
Acústica , Edema/diagnóstico , Insuficiência Cardíaca/complicações , Fonação , Acústica da Fala , Medida da Produção da Fala , Prega Vocal/fisiopatologia , Distúrbios da Voz/diagnóstico , Qualidade da Voz , Idoso , Idoso de 80 Anos ou mais , Diuréticos/uso terapêutico , Edema/tratamento farmacológico , Edema/etiologia , Edema/fisiopatologia , Feminino , Insuficiência Cardíaca/diagnóstico , Insuficiência Cardíaca/tratamento farmacológico , Insuficiência Cardíaca/fisiopatologia , Humanos , Pulmão/fisiopatologia , Masculino , Pessoa de Meia-Idade , Fonação/efeitos dos fármacos , Projetos Piloto , Valor Preditivo dos Testes , Respiração , Resultado do Tratamento , Prega Vocal/efeitos dos fármacos , Distúrbios da Voz/tratamento farmacológico , Distúrbios da Voz/etiologia , Distúrbios da Voz/fisiopatologia , Qualidade da Voz/efeitos dos fármacosAssuntos
American Heart Association , Circulação Assistida , Aprovação de Equipamentos , Circulação Extracorpórea , Circulação Assistida/instrumentação , Circulação Assistida/métodos , Intervalo Livre de Doença , Circulação Extracorpórea/instrumentação , Circulação Extracorpórea/métodos , Feminino , Insuficiência Cardíaca/mortalidade , Insuficiência Cardíaca/fisiopatologia , Insuficiência Cardíaca/terapia , Humanos , Masculino , Guias de Prática Clínica como Assunto , Taxa de Sobrevida , Estados Unidos/epidemiologia , United States Food and Drug AdministrationRESUMO
IMPORTANCE: Iron deficiency is present in approximately 50% of patients with heart failure with reduced left ventricular ejection fraction (HFrEF) and is an independent predictor of reduced functional capacity and mortality. However, the efficacy of inexpensive readily available oral iron supplementation in heart failure is unknown. OBJECTIVE: To test whether therapy with oral iron improves peak exercise capacity in patients with HFrEF and iron deficiency. DESIGN, SETTING, AND PARTICIPANTS: Phase 2, double-blind, placebo-controlled randomized clinical trial of patients with HFrEF (<40%) and iron deficiency, defined as a serum ferritin level of 15 to 100 ng/mL or a serum ferritin level of 101 to 299 ng/mL with transferrin saturation of less than 20%. Participants were enrolled between September 2014 and November 2015 at 23 US sites. INTERVENTIONS: Oral iron polysaccharide (n = 111) or placebo (n = 114), 150 mg twice daily for 16 weeks. MAIN OUTCOMES AND MEASURES: The primary end point was a change in peak oxygen uptake (VÌo2) from baseline to 16 weeks. Secondary end points were change in 6-minute walk distance, plasma N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels, and health status as assessed by Kansas City Cardiomyopathy Questionnaire (KCCQ, range 0-100, higher scores reflect better quality of life). RESULTS: Among 225 randomized participants (median age, 63 years; 36% women) 203 completed the study. The median baseline peak VÌo2 was 1196 mL/min (interquartile range [IQR], 887-1448 mL/min) in the oral iron group and 1167 mL/min (IQR, 887-1449 mL/min) in the placebo group. The primary end point, change in peak VÌo2 at 16 weeks, did not significantly differ between the oral iron and placebo groups (+23 mL/min vs -2 mL/min; difference, 21 mL/min [95% CI, -34 to +76 mL/min]; P = .46). Similarly, at 16 weeks, there were no significant differences between treatment groups in changes in 6-minute walk distance (-13 m; 95% CI, -32 to 6 m), NT-proBNP levels (159; 95% CI, -280 to 599 pg/mL), or KCCQ score (1; 95% CI, -2.4 to 4.4), all P > .05. CONCLUSIONS AND RELEVANCE: Among participants with HFrEF with iron deficiency, high-dose oral iron did not improve exercise capacity over 16 weeks. These results do not support use of oral iron supplementation in patients with HFrEF. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT02188784.
Assuntos
Tolerância ao Exercício , Ferritinas/sangue , Insuficiência Cardíaca/fisiopatologia , Compostos de Ferro/administração & dosagem , Deficiências de Ferro , Consumo de Oxigênio , Volume Sistólico/fisiologia , Administração Oral , Idoso , Método Duplo-Cego , Feminino , Nível de Saúde , Insuficiência Cardíaca/complicações , Insuficiência Cardíaca/metabolismo , Humanos , Compostos de Ferro/efeitos adversos , Masculino , Pessoa de Meia-Idade , Peptídeo Natriurético Encefálico/sangue , Fragmentos de Peptídeos/sangue , Qualidade de Vida , Fatores de Tempo , Transferrina/metabolismo , Resultado do Tratamento , Teste de CaminhadaRESUMO
Approximately half of patients with heart failure have preserved ejection fraction. There is no proven treatment that improves outcome. The pathophysiology of heart failure with preserved ejection fraction is complex and includes left ventricular systolic and diastolic dysfunction, pulmonary vascular disease, endothelial dysfunction, and peripheral abnormalities. Multiple lines of evidence point to impaired nitric oxide (NO)-cGMP bioavailability as playing a central role in each of these abnormalities. In contrast to traditional organic nitrate therapies, an alternative strategy to restore NO-cGMP signaling is via inorganic nitrite. Inorganic nitrite, previously considered to be an inert byproduct of NO metabolism, functions as an important in vivo reservoir for NO generation, particularly under hypoxic and acidosis conditions. As such, inorganic nitrite becomes most active at times of greater need for NO signaling, as during exercise when left ventricular filling pressures and pulmonary artery pressures increase. Herein, we present the rationale and design for the INDIE-HFpEF trial (Inorganic Nitrite Delivery to Improve Exercise Capacity in Heart Failure with Preserved Ejection Fraction), which is a multicenter, randomized, double-blind, placebo-controlled cross-over study assessing the effect of inhaled inorganic nitrite on peak exercise capacity, conducted in the National Heart, Lung, and Blood Institute-sponsored Heart Failure Clinical Research Network. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT02742129.
Assuntos
Tolerância ao Exercício/fisiologia , Insuficiência Cardíaca/fisiopatologia , Nitratos/administração & dosagem , Ensaios Clínicos Controlados Aleatórios como Assunto/métodos , Volume Sistólico/fisiologia , Função Ventricular Esquerda/fisiologia , Teste de Esforço , Tolerância ao Exercício/efeitos dos fármacos , Insuficiência Cardíaca/tratamento farmacológico , Humanos , Função Ventricular Esquerda/efeitos dos fármacosRESUMO
Advances in cardiac imaging have resulted in greater recognition of cardiac amyloidosis in everyday clinical practice, but the diagnosis continues to be made in patients with late-stage disease, suggesting that more needs to be done to improve awareness of its clinical manifestations and the potential of therapeutic intervention to improve prognosis. Light chain cardiac amyloidosis, in particular, if recognized early and treated with targeted plasma cell therapy, can be managed very effectively. For patients with transthyretin amyloidosis, there are numerous therapies that are currently in late-phase clinical trials. In this review, we address common questions encountered in clinical practice regarding etiology, clinical presentation, diagnosis, and management of cardiac amyloidosis, focusing on recent important developments in cardiac imaging and biochemical diagnosis. The aim is to show how a systematic approach to the evaluation of suspected cardiac amyloidosis can impact the prognosis of patients in the modern era.
Assuntos
Amiloidose/diagnóstico , Cardiomiopatias/diagnóstico , Idoso , Amiloidose/terapia , Cardiomiopatias/terapia , Humanos , Pessoa de Meia-IdadeRESUMO
BACKGROUND: While abnormal left ventricular (LV) global longitudinal strain (GLS) has been described in patients with heart failure with preserved ejection fraction (HFpEF), its prevalence and clinical significance are poorly understood. METHODS AND RESULTS: Patients enrolled in the RELAX trial of sildenafil in HFpEF (LV ejection fraction ≥50%) in whom two-dimensional, speckle-tracking LV GLS was possible (n = 187) were analysed. The distribution of LV GLS and its associations with clinical characteristics, LV structure and function, biomarkers, exercise capacity and quality of life were assessed. Baseline median LV GLS was -14.6% (25th and 75th percentile, -17.0% and -11.9%, respectively) and abnormal (≥ - 16%) in 122/187 (65%) patients. Patients in the tertile with the best LV GLS had lower N-terminal pro-brain natriuretic peptide (NT-proBNP) [median 505 pg/mL (161, 1065) vs. 875 pg/mL (488, 1802), P = 0.008) and lower collagen III N-terminal propeptide (PIIINP) levels [median 6.7 µg/L (5.1, 8.1) vs. 8.1 µg/L (6.5, 10.5), P = 0.001] compared with the tertile with the worst LV GLS. There was also a modest linear relationship with LV GLS and log-transformed NT-proBNP and PIIINP (r = 0.29, P < 0.001 and r = 0.19, P = 0.009, respectively). We observed no linear association of LV GLS with Minnesota Living with Heart Failure scores, 6-min walk distance, peak oxygen consumption, or expiratory minute ventilation/carbon dioxide excretion slope. CONCLUSIONS: Impaired LV GLS is common among HFpEF patients, indicating the presence of covert systolic dysfunction despite normal LV ejection fraction. Impaired LV GLS was associated with biomarkers of wall stress and collagen synthesis and diastolic dysfunction but not with quality of life or exercise capacity, suggesting other processes may be more responsible for these aspects of the HFpEF syndrome.
Assuntos
Insuficiência Cardíaca Sistólica/fisiopatologia , Ventrículos do Coração/fisiopatologia , Contração Miocárdica/fisiologia , Volume Sistólico/fisiologia , Função Ventricular Esquerda/fisiologia , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/sangue , Método Duplo-Cego , Ecocardiografia , Tolerância ao Exercício/fisiologia , Feminino , Seguimentos , Insuficiência Cardíaca Sistólica/sangue , Insuficiência Cardíaca Sistólica/diagnóstico , Ventrículos do Coração/diagnóstico por imagem , Humanos , Masculino , Pessoa de Meia-Idade , Peptídeo Natriurético Encefálico/sangue , Consumo de Oxigênio , Fragmentos de Peptídeos/sangue , Pró-Colágeno/sangue , Qualidade de Vida , Estudos Retrospectivos , Fatores de TempoRESUMO
Given the emerging recognition of left atrial structure and function as an important marker of disease in heart failure with preserved ejection fraction (HF-pEF), we investigated the association between left atrial volume and function with markers of disease severity and cardiac structure in HF-pEF. We studied 100 patients enrolled in the PhosphdiesteRasE-5 Inhibition to Improve CLinical Status and EXercise Capacity in Diastolic Heart Failure (RELAX) trial who underwent cardiac magnetic resonance (CMR), cardiopulmonary exercise testing, and blood collection before randomization. Maximal left atrial volume index (LAVi; N = 100), left atrial emptying fraction (LAEF; N = 99; including passive and active components (LAEFP, LAEFA; N = 80, 79, respectively) were quantified by CMR. After adjustment for multiple testing, maximal LAVi was only associated with age (ρ = 0.39), transmitral filling patterns (medial E/e' ρ = 0.43), and N-terminal pro-BNP (NT-proBNP; ρ = 0.65; all p<0.05). Lower LAEF was associated with older age, higher transmitral E/A ratio and higher NT-proBNP. Peak VO2 and VE/VCO2 slope were not associated with left atrial structure or function. After adjustment for age, sex, transmitral E/A ratio, CMR LV mass, LV ejection fraction, and creatinine clearance, NT-proBNP remained associated with maximal LAVi (ß = 0.028, p = 0.0007) and total LAEF (ß = -0.033, p = 0.001). Passive and active LAEF were most strongly associated with age and NT-proBNP, but not gas exchange or other markers of ventricular structure or filling properties. Left atrial volume and emptying function are associated most strongly with NT-proBNP and diastolic filling properties, but not significantly with gas exchange, in HFpEF. Further research to explore the relevance of left atrial structure and function in HF-pEF is warranted.
Assuntos
Átrios do Coração/patologia , Insuficiência Cardíaca/patologia , Insuficiência Cardíaca/fisiopatologia , Volume Sistólico , Idoso , Envelhecimento/metabolismo , Envelhecimento/fisiologia , Biomarcadores/metabolismo , Exercício Físico , Feminino , Fibrose , Insuficiência Cardíaca/metabolismo , Hemodinâmica , Humanos , Masculino , Pessoa de Meia-Idade , Peptídeo Natriurético Encefálico/metabolismo , Tamanho do Órgão , Fragmentos de Peptídeos/metabolismoAssuntos
Broncodilatadores/uso terapêutico , Hemodinâmica/efeitos dos fármacos , Hipertensão Pulmonar/tratamento farmacológico , Óxido Nítrico/uso terapêutico , Administração por Inalação , Broncodilatadores/administração & dosagem , Feminino , Humanos , Hipertensão Pulmonar/fisiopatologia , Masculino , Pessoa de Meia-Idade , Óxido Nítrico/administração & dosagemRESUMO
OBJECTIVES: This study sought to investigate relationships between insulin-like growth factor-binding protein-7 (IGFBP7) and parameters of diastolic function or functional capacity in patients with heart failure and preserved ejection fraction (HFpEF) who were randomized to receive sildenafil or placebo. BACKGROUND: IGFBP7 was previously found to be associated with diastolic function in heart failure with reduced ejection fraction, but it is unclear whether these associations are present in HFpEF. METHODS: At baseline and 24 weeks, IGFBP7, imaging studies, and peak oxygen consumption (Vo2max) were obtained and compared in 160 patients with HFpEF who were randomized to receive sildenafil or placebo. RESULTS: Patients with supramedian baseline IGFBP7 concentrations were older, had signs of systemic congestion and worse renal function, and had higher concentrations of prognostic heart failure biomarkers including amino-terminal pro-B-type natriuretic peptide (p < 0.05). Higher baseline IGFBP7 was modestly correlated with worse diastolic function: higher E velocity (Spearman correlation [ρ] = 0.40), E/E' (ρ = 0.40), left atrial volume index (ρ = 0.39), and estimated right ventricular systolic pressure (ρ = 0.41; all p < 0.001) and weakly correlated with transmitral E/A (ρ = 0.26; p = 0.006). Notably, change in IGFBP7 was significantly correlated with change in E, E/A, E/E', and right ventricular systolic pressure. Elevated baseline IGFBP7 was associated with lower baseline Vo2max (13.2 vs. 11.1 ml/min/kg; p < 0.001), and change in IGFBP7 was weakly inversely correlated with change in Vo2max (ρ = -0.19; p = 0.01). Subjects receiving sildenafil had a decrease in IGFBP7 over 24 weeks, in contrast to placebo-treated patients (median change in IGFBP7 -1.5 vs. +13.6 ng/ml; p < 0.001). CONCLUSIONS: In patients with HFpEF, IGFBP7 may be a novel biomarker of diastolic function and exercise capacity.
Assuntos
Insuficiência Cardíaca Diastólica/sangue , Proteínas de Ligação a Fator de Crescimento Semelhante a Insulina/sangue , Consumo de Oxigênio , Volume Sistólico , Atividades Cotidianas , Idoso , Biomarcadores/sangue , Feminino , Insuficiência Cardíaca/sangue , Insuficiência Cardíaca/tratamento farmacológico , Insuficiência Cardíaca/fisiopatologia , Insuficiência Cardíaca Diastólica/tratamento farmacológico , Insuficiência Cardíaca Diastólica/fisiopatologia , Humanos , Masculino , Pessoa de Meia-Idade , Peptídeo Natriurético Encefálico/sangue , Fragmentos de Peptídeos/sangue , Ensaios Clínicos Controlados Aleatórios como Assunto , Citrato de Sildenafila/uso terapêutico , Vasodilatadores/uso terapêuticoRESUMO
BACKGROUND: Conversations about goals of care and cardiopulmonary resuscitation (CPR)/intubation for patients with advanced heart failure can be difficult. This study examined the impact of a video decision support tool and patient checklist on advance care planning for patients with heart failure. METHODS: This was a multisite, randomized, controlled trial of a video-assisted intervention and advance care planning checklist versus a verbal description in 246 patients ≥64 years of age with heart failure and an estimated likelihood of death of >50% within 2 years. Intervention participants received a verbal description for goals of care (life-prolonging care, limited care, and comfort care) and CPR/intubation plus a 6-minute video depicting the 3 levels of care, CPR/intubation, and an advance care planning checklist. Control subjects received only the verbal description. The primary analysis compared the proportion of patients preferring comfort care between study arms immediately after the intervention. Secondary outcomes were CPR/intubation preferences and knowledge (6-item test; range, 0-6) after intervention. RESULTS: In the intervention group, 27 (22%) chose life-prolonging care, 31 (25%) chose limited care, 63 (51%) selected comfort care, and 2 (2%) were uncertain. In the control group, 50 (41%) chose life-prolonging care, 27 (22%) selected limited care, 37 (30%) chose comfort care, and 8 (7%) were uncertain (P<0.001). Intervention participants (compared with control subjects) were more likely to forgo CPR (68% versus 35%; P<0.001) and intubation (77% versus 48%; P<0.001) and had higher mean knowledge scores (4.1 versus 3.0; P<0.001). CONCLUSIONS: Patients with heart failure who viewed a video were more informed, more likely to select a focus on comfort, and less likely to desire CPR/intubation compared with patients receiving verbal information only. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01589120.