RESUMO
INTRODUCTION: Abuse of anabolic-androgenic steroids (AAS) has been linked to a variety of different cardiovascular (CV) side effects, but still the clinical effects of AAS abuse on CV risk are not clear. The aim of this study was to assess the CV phenotype of a large cohort of men with long-term AAS use compared with strength-trained athletes without AAS use. METHODS: Fifty one strength-trained men with ≥3 years of AAS use was compared with twenty one strength-trained competing athletes. We verified substance abuse and non-abuse by blood and urine analyses. The participants underwent comprehensive CV evaluation including laboratory analyses, 12-lead ECG with measurement of QT dispersion, exercise ECG, 24 h ECG with analyses of heart rate variability, signal averaged ECG, basic transthoracic echocardiography, and coronary computed tomography angiography (CCTA). RESULTS: Hemoglobin levels and hematocrit were higher among the AAS users compared with non-users (16.8 vs. 15.0 g/dl, and 0.50% vs. 0.44%, respectively, both p < 0.01) and HDL cholesterol significantly lower (0.69 vs. 1.25 mmol/L, p < 0.01). Maximal exercise capacity was 270 and 280 W in the AAS and the non-user group, respectively (p = 0.04). Echocardiography showed thicker intraventricular septum and left ventricular (LV) posterior wall among AAS users (p < 0.01 for both), while LV ejection fraction was lower (50 vs. 54%, p = 0.02). Seven AAS users (17%) had evidence of coronary artery disease on CCTA. There were no differences in ECG measures between the groups. CONCLUSIONS: A divergent CV phenotype dominated by increased CV risk, accelerated coronary artery disease, and concentric myocardial hypertrophy was revealed among the AAS users.
Assuntos
Anabolizantes , Doença da Artéria Coronariana , Transtornos Relacionados ao Uso de Substâncias , Anabolizantes/efeitos adversos , Atletas , Humanos , Fenótipo , Esteroides/efeitos adversos , Congêneres da Testosterona/efeitos adversosRESUMO
OBJECTIVES: To evaluate the clinical utility and feasibility of a hybrid technique for obtaining vascular hemostasis by combining a suture- and a collagen-mediated system after transfemoral transcatheter aortic valve implantation (TF TAVI) in a real-world setting. METHODS: In 75 consecutive TF TAVI procedures, we investigated a hybrid closing method to achieve hemostasis at the large bore puncture site using a combination of one presuture closure system (ProGlide) and one collagen-mediated system (Angio-Seal). Vascular complications at puncture site were recorded until discharge. RESULTS: Successful hemostasis by the hybrid technique was achieved in 74 out of 75 patients, and the method was well tolerated by all patients. In 73 patients, (97.3%) neither puncture site related complications nor serious early or late bleedings were observed during a median hospital stay of 2 days postprocedure. CONCLUSION: This single-center registry study indicates that a percutaneous hybrid closure technique is safe and efficacious in closing large bore arteriotomies. It is an easy and reliable technique that may contribute to simplifying TAVI procedures. STUDY REGISTRATION: The data was collected from an internal quality control registry on treatment of patients with valvular heart disease with or without coronary artery disease, No 2014/17280, Oslo University Hospital, Ullevål.
Assuntos
Valva Aórtica/cirurgia , Cateterismo Periférico , Artéria Femoral , Hemorragia/prevenção & controle , Técnicas Hemostáticas/instrumentação , Procedimentos Cirúrgicos sem Sutura/instrumentação , Substituição da Valva Aórtica Transcateter , Dispositivos de Oclusão Vascular , Idoso , Idoso de 80 Anos ou mais , Cateterismo Periférico/efeitos adversos , Estudos de Viabilidade , Feminino , Hemorragia/etiologia , Técnicas Hemostáticas/efeitos adversos , Humanos , Masculino , Punções , Sistema de Registros , Estudos Retrospectivos , Procedimentos Cirúrgicos sem Sutura/efeitos adversos , Fatores de Tempo , Substituição da Valva Aórtica Transcateter/efeitos adversos , Resultado do TratamentoRESUMO
BACKGROUND: Self-care is key to the daily management of chronic heart failure (HF). After discharge from hospital, patients may struggle to recognize and respond to worsening HF symptoms. Failure to monitor and respond to HF symptoms may lead to unnecessary hospitalizations. OBJECTIVE: This study aimed to (1) determine the feasibility of lung impedance measurements and a symptom diary to monitor HF symptoms daily at home for 30 days following hospital discharge and (2) determine daily changes in HF symptoms of pulmonary edema, lung impedance measurements, and if self-care behavior improves over time when patients use these self-care monitoring tools. METHODS: This study used a prospective longitudinal design including patients from cardiology wards in 2 university hospitals-one in Norway and one in Lithuania. Data on HF symptoms and pulmonary edema were collected from 10 participants (mean age 64.5 years; 90% (9/10) male) with severe HF (New York Heart Association classes III and IV) who were discharged home after being hospitalized for an HF condition. HF symptoms were self-reported using the Memorial Symptom Assessment Scale for Heart Failure. Pulmonary edema was measured by participants using a noninvasive lung impedance monitor, the CardioSet Edema Guard Monitor. Informal caregivers aided the participants with the noninvasive measurements. RESULTS: The prevalence and burden of shortness of breath varied from participants experiencing them daily to never, whereas lung impedance measurements varied for individual participants and the group participants, as a whole. Self-care behavior score improved significantly (P=.007) from a median of 56 (IQR range 22-75) at discharge to a median of 81 (IQR range 72-98) 30 days later. CONCLUSIONS: Noninvasive measurement of lung impedance daily and the use of a symptom diary were feasible at home for 30 days in HF patients. Self-care behavior significantly improved after 30 days of using a symptom diary and measuring lung impedance at home. Further research is needed to determine if daily self-care monitoring of HF signs and symptoms, combined with daily lung impedance measurements, may reduce hospital readmissions.
Assuntos
Impedância Elétrica/uso terapêutico , Insuficiência Cardíaca/terapia , Autocuidado/métodos , Telemedicina/métodos , Idoso , Cuidadores , Feminino , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Alta do Paciente , Estudos Prospectivos , AutorrelatoRESUMO
BACKGROUND: Reduced left ventricular ejection fraction (LVEF) after acute myocardial infarction (MI) increases risk of cardiovascular (CV) hospitalizations, but evidence regarding its association with non-CV outcome is scarce. We investigated the association between LVEF and adjudicated cause-specific hospitalizations following MI complicated with low LVEF or overt heart failure (HF). METHODS: In an individual patient data meta-analysis of 19,740 patients from 3 large randomized trials, Fine and Gray competing risk modeling was performed to study the association between LVEF and hospitalization types. RESULTS: The most common cause of hospitalization was non-CV (nâ¯=â¯2,368 for HF, nâ¯=â¯1,554 for MI, and nâ¯=â¯3,703 for non-CV). All types of hospitalizations significantly increased with decreasing LVEF. The absolute risk increase associated with LVEF âª25% (vs LVEF â«35%) was 15.5% (95% CI 13.4-17.5) for HF, 4.7% (95% CI 3.0-6.4) for MI, and 10.4% (95% CI 8.0-12.8) for non-CV hospitalization. On a relative scale, after adjusting for confounders, each 5-point decrease in LVEF was associated with an increased risk of HF (hazard ratio [HR] 1.15, 95% CI 1.12-1.18), MI (HR 1.06, 95% CI 1.03-1.10), and non-CV hospitalization (HR 1.03, 95% CI 1.01-1.05). CONCLUSIONS: In a high-risk population with complicated acute MI, the absolute risk increase in non-CV hospitalizations associated with LVEF âª25% was two thirds of the absolute risk increase in HF hospitalizations and twice the absolute risk increase in MI hospitalizations. LVEF was an independent predictor of all types of hospitalization and appears as an integrative marker of sicker patient status.
Assuntos
Insuficiência Cardíaca/etiologia , Hospitalização/tendências , Infarto do Miocárdio/complicações , Volume Sistólico/fisiologia , Disfunção Ventricular Esquerda/etiologia , Função Ventricular Esquerda/fisiologia , Idoso , Causas de Morte/tendências , Europa (Continente)/epidemiologia , Feminino , Seguimentos , Insuficiência Cardíaca/mortalidade , Insuficiência Cardíaca/fisiopatologia , Ventrículos do Coração/fisiopatologia , Humanos , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/mortalidade , Fatores de Risco , Taxa de Sobrevida/tendências , Fatores de Tempo , Disfunção Ventricular Esquerda/mortalidade , Disfunção Ventricular Esquerda/fisiopatologiaRESUMO
BACKGROUND: Many patients with heart failure (HF) are treated with warfarin or non-vitamin K oral anticoagulants (NOACs). Randomized outcome-driven comparisons of different anticoagulant strategies in HF are lacking. Data from international, government-mandated registries may be useful in understanding the real-life use of various anticoagulants and how they are linked to outcomes. STUDY QUESTION: To assess 2015 annual all-cause mortality, myocardial infarction, and stroke rates co-reported for warfarin and NOACs in subjects with and without HF in the US Food and Drug Administration Adverse Event Reporting System (FAERS) database. STUDY DESIGN: We extracted and examined outcome cases in subjects with HF and on warfarin, dabigatran, rivaroxaban, apixaban, or edoxaban and stratified these according to anticoagulants. MEASURES AND OUTCOMES: Annual all-cause mortality, myocardial infarction, and stroke in FAERS. ANALYSIS METHOD: Odds ratio (OR) and χ(Equation is included in full-text article.)for oral anticoagulants from FAERS with and without HF among complete primary reports issued in 2015. RESULTS: FAERS reported 137,026 HF cases, with death co-reported in 42,942 (31.3%). In total, 11,278 (8.2%) HF patients were treated with anticoagulants, with more prescribed warfarin (n = 8260) than all NOACs combined (n = 3018). Very few reports for edoxaban were available. Warfarin consistently displayed a signal for excess adverse events compared to NOACs: OR (95% confidence interval) for the composite of mortality, myocardial infarction, and stroke were 1.91 (1.76-2.07) versus apixaban, 1.92 (1.81-2.03) versus dabigatran, 4.09 (3.38-4.37) versus rivaroxaban, and 2.64 (2.53-2.76) versus all NOACs combined (all P < 0.001). Warfarin, compared to all NOACs combined, demonstrated higher rates of all-cause mortality [OR = 2.69 (95% confidence interval, 2.49-2.90)], myocardial infarction [5.30 (4.17-6.74)], stroke [OR = 8.85 (6.61-11.84)], and ischemic stroke [OR = 12.73 (8.87-18.27); all P < 0.001]. CONCLUSIONS: Annual 2015 FAERS profiles in HF patients reveal that warfarin was numerically dominant. Warfarin was associated with higher risk of death, myocardial infarction, and stroke compared to NOACs. These observational data provide real-world insight into a potential safety benefit of NOACs over warfarin in the setting of HF.
Assuntos
Anticoagulantes/efeitos adversos , Insuficiência Cardíaca/tratamento farmacológico , Varfarina/efeitos adversos , Administração Oral , Sistemas de Notificação de Reações Adversas a Medicamentos/estatística & dados numéricos , Anticoagulantes/administração & dosagem , Anticoagulantes/uso terapêutico , Feminino , Insuficiência Cardíaca/complicações , Insuficiência Cardíaca/mortalidade , Humanos , Masculino , Infarto do Miocárdio/complicações , Infarto do Miocárdio/epidemiologia , Acidente Vascular Cerebral/complicações , Acidente Vascular Cerebral/epidemiologia , Resultado do Tratamento , Estados Unidos/epidemiologia , United States Food and Drug Administration , Vitamina K/antagonistas & inibidores , Varfarina/uso terapêuticoRESUMO
BACKGROUND: Noninvasive telemonitoring (TM) can be used in heart failure (HF) patients to perform early detection of decompensation at home, prevent unnecessary health care utilization, and decrease health care costs. However, the evidence is not sufficient to be part of HF guidelines for follow-up care, and we have no knowledge of how TM is used in the Nordic Baltic region. OBJECTIVE: The aim of this study was to describe health care professionals' (HCPs) perception of and presumed experience with noninvasive TM in daily HF patient care, perspectives of the relevance of and reasons for applying noninvasive TM, and barriers to the use of noninvasive TM. METHODS: A cross-sectional survey was performed between September and December 2016 in Norway and Lithuania with physicians and nurses treating HF patients at either a hospital ward or an outpatient clinic. A total of 784 questionnaires were sent nationwide by postal mail to 107 hospitals. The questionnaire consisted of 43 items with close- and open-ended questions. In Norway, the response rate was 68.7% (226/329), with 57 of 60 hospitals participating, whereas the response rate was 68.1% (310/455) in Lithuania, with 41 of 47 hospitals participating. Responses to the closed questions were analyzed using descriptive statistics, and the open-ended questions were analyzed using summative content analysis. RESULTS: This study showed that noninvasive TM is not part of the current daily clinical practice in Norway or Lithuania. A minority of HCPs responded to be familiar with noninvasive TM in HF care in Norway (48/226, 21.2%) and Lithuania (64/310, 20.6%). Approximately half of the HCPs in both countries perceived noninvasive TM to be relevant in follow-up of HF patients in Norway (131/226, 58.0%) and Lithuania (172/310, 55.5%). For physicians in both countries and nurses in Norway, the 3 most mentioned reasons for introducing noninvasive TM were to improve self-care, to reduce hospitalizations, and to provide high-quality care, whereas the Lithuanian nurses described ability to treat more patients and to reduce their workload as reasons for introducing noninvasive TM. The main barriers to implement noninvasive TM were lack of funding from health care authorities or the Territorial Patient Fund. Moreover, HCPs perceive that HF patients themselves could represent barriers because of their physical or mental condition in addition to a lack of internet access. CONCLUSIONS: HCPs in Norway and Lithuania are currently nonusers of TM in daily HF care. However, they perceive a future with TM to improve the quality of care for HF patients. Financial barriers and HF patients' condition may have an impact on the use of TM, whereas sufficient funding from health care authorities and improved knowledge may encourage the more widespread use of TM in the Nordic Baltic region and beyond.
Assuntos
Pessoal de Saúde/normas , Insuficiência Cardíaca/terapia , Telemedicina/métodos , Estudos Transversais , Feminino , Insuficiência Cardíaca/patologia , Serviços de Assistência Domiciliar , Humanos , Masculino , Autocuidado , Inquéritos e QuestionáriosRESUMO
Aims: Recent guidelines recommend that patients with heart failure and left ventricular ejection fraction (LVEF) 40-49% should be managed similar to LVEF ≥ 50%. We investigated the effect of beta-blockers according to LVEF in double-blind, randomized, placebo-controlled trials. Methods and results: Individual patient data meta-analysis of 11 trials, stratified by baseline LVEF and heart rhythm (Clinicaltrials.gov: NCT0083244; PROSPERO: CRD42014010012). Primary outcomes were all-cause mortality and cardiovascular death over 1.3 years median follow-up, with an intention-to-treat analysis. For 14 262 patients in sinus rhythm, median LVEF was 27% (interquartile range 21-33%), including 575 patients with LVEF 40-49% and 244 ≥ 50%. Beta-blockers reduced all-cause and cardiovascular mortality compared to placebo in sinus rhythm, an effect that was consistent across LVEF strata, except for those in the small subgroup with LVEF ≥ 50%. For LVEF 40-49%, death occurred in 21/292 [7.2%] randomized to beta-blockers compared to 35/283 [12.4%] with placebo; adjusted hazard ratio (HR) 0.59 [95% confidence interval (CI) 0.34-1.03]. Cardiovascular death occurred in 13/292 [4.5%] with beta-blockers and 26/283 [9.2%] with placebo; adjusted HR 0.48 (95% CI 0.24-0.97). Over a median of 1.0 years following randomization (n = 4601), LVEF increased with beta-blockers in all groups in sinus rhythm except LVEF ≥50%. For patients in atrial fibrillation at baseline (n = 3050), beta-blockers increased LVEF when < 50% at baseline, but did not improve prognosis. Conclusion: Beta-blockers improve LVEF and prognosis for patients with heart failure in sinus rhythm with a reduced LVEF. The data are most robust for LVEF < 40%, but similar benefit was observed in the subgroup of patients with LVEF 40-49%.
Assuntos
Antagonistas Adrenérgicos beta/uso terapêutico , Insuficiência Cardíaca , Volume Sistólico/fisiologia , Idoso , Fibrilação Atrial , Método Duplo-Cego , Feminino , Insuficiência Cardíaca/tratamento farmacológico , Insuficiência Cardíaca/mortalidade , Insuficiência Cardíaca/fisiopatologia , Humanos , Masculino , Pessoa de Meia-Idade , Placebos , Ensaios Clínicos Controlados Aleatórios como AssuntoRESUMO
Compared to men, women with heart failure (HF) are often older, smoke less, and have more preserved ejection fraction (EF) and hypertensive HF rather than HF of ischemic etiology. Gender-stratified outcomes on comorbidities data in HF are scarce. Women have traditionally been underrepresented in HF trials. Although data suggest that overall prognosis may be better in women, they experience lower quality of life with greater functional impairment from HF compared to men. Gender differences have been reported for comorbid diabetes, chronic obstructive pulmonary disease, renal dysfunction, anemia, and depression and may explain gender disparity in outcomes. However, possible confounding of comorbidities with known prognostic determinants in HF (such as EF) as well as gender differences in the utilization of medical therapies obscures interpretation. In this review, we will explore the evidence for gender differences in non-cardiovascular comorbidities in HF. Our findings may guide clinicians to individualize HF care, according to best practice, in the hope of improving prognosis for this chronic and debilitating condition.
Assuntos
Insuficiência Cardíaca/epidemiologia , Anemia/epidemiologia , Artrite/epidemiologia , Comorbidade , Depressão/epidemiologia , Diabetes Mellitus/epidemiologia , Feminino , Insuficiência Cardíaca/fisiopatologia , Humanos , Masculino , Doença Pulmonar Obstrutiva Crônica/epidemiologia , Insuficiência Renal Crônica/epidemiologia , Fatores SexuaisRESUMO
BACKGROUND: Atrial fibrillation and heart failure often coexist, causing substantial cardiovascular morbidity and mortality. ß blockers are indicated in patients with symptomatic heart failure with reduced ejection fraction; however, the efficacy of these drugs in patients with concomitant atrial fibrillation is uncertain. We therefore meta-analysed individual-patient data to assess the efficacy of ß blockers in patients with heart failure and sinus rhythm compared with atrial fibrillation. METHODS: We extracted individual-patient data from ten randomised controlled trials of the comparison of ß blockers versus placebo in heart failure. The presence of sinus rhythm or atrial fibrillation was ascertained from the baseline electrocardiograph. The primary outcome was all-cause mortality. Analysis was by intention to treat. Outcome data were meta-analysed with an adjusted Cox proportional hazards regression. The study is registered with Clinicaltrials.gov, number NCT0083244, and PROSPERO, number CRD42014010012. FINDINGS: 18,254 patients were assessed, and of these 13,946 (76%) had sinus rhythm and 3066 (17%) had atrial fibrillation at baseline. Crude death rates over a mean follow-up of 1·5 years (SD 1·1) were 16% (2237 of 13,945) in patients with sinus rhythm and 21% (633 of 3064) in patients with atrial fibrillation. ß-blocker therapy led to a significant reduction in all-cause mortality in patients with sinus rhythm (hazard ratio 0·73, 0·67-0·80; p<0·001), but not in patients with atrial fibrillation (0·97, 0·83-1·14; p=0·73), with a significant p value for interaction of baseline rhythm (p=0·002). The lack of efficacy for the primary outcome was noted in all subgroups of atrial fibrillation, including age, sex, left ventricular ejection fraction, New York Heart Association class, heart rate, and baseline medical therapy. INTERPRETATION: Based on our findings, ß blockers should not be used preferentially over other rate-control medications and not regarded as standard therapy to improve prognosis in patients with concomitant heart failure and atrial fibrillation. FUNDING: Menarini Farmaceutica Internazionale (administrative support grant).
Assuntos
Antagonistas Adrenérgicos beta/uso terapêutico , Fibrilação Atrial/tratamento farmacológico , Fibrilação Atrial/mortalidade , Insuficiência Cardíaca/tratamento farmacológico , Insuficiência Cardíaca/mortalidade , Fibrilação Atrial/complicações , Eletrocardiografia , Insuficiência Cardíaca/complicações , Humanos , Tempo de Internação/estatística & dados numéricos , Admissão do Paciente/estatística & dados numéricos , Ensaios Clínicos Controlados Aleatórios como Assunto , Acidente Vascular Cerebral/mortalidadeRESUMO
Heart failure (HF) is predominantly a disease that affects the elderly population, a cohort in which comorbidities are common. The majority of comorbidities and the degree of their severity have prognostic implications in HF. Polypharmacy in HF is common, has increased throughout the past 2 decades, and may pose a risk for adverse drug interactions, accidental overdosing, or medication nonadherence. Polypharmacy, in particular in the elderly, is rarely assessed in traditional clinical trials, highlighting a need for entirely novel HF research strategies.
Assuntos
Insuficiência Cardíaca/complicações , Insuficiência Cardíaca/tratamento farmacológico , Polimedicação , Fatores Etários , Idoso , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/epidemiologia , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/prevenção & controle , Humanos , Fatores de RiscoRESUMO
Hypertension, coronary artery disease and heart failure affect over half of the adult population in most Western societies, and are prime causes of CV morbidity and mortality. With the ever-increasing worldwide prevalence of CV disease due to ageing and the "diabetes" pandemic, guideline groups have recognized the importance of achieving cardioprotection in affected individuals as well as in those at risk for future CV events. The renin-angiotensin-aldosterone system (RAAS) is the most important system controlling blood pressure (BP), cardiovascular and renal function in man. As our understanding of the crucial role of RAAS in the pathogenesis of most, if not all, CV disease has expanded over the past decades, so has the development of drugs targeting its individual components. Angiotensin-converting enzyme inhibitors (ACEi), Ang-II receptor blockers (ARB), and mineralcorticoid receptor antagonists (MRA) have been evaluated in large clinical trials for their potential to mediate cardioprotection, singly or in combination. Direct renin inhibitors are currently under scrutiny, as well as novel dual-acting RAAS-blocking agents. Herein, we review the evidence generated from large-scale clinical trials of cardioprotection achieved through RAAS-blockade.
Assuntos
Cardiotônicos/farmacologia , Sistema Renina-Angiotensina/fisiologia , Antagonistas de Receptores de Angiotensina/farmacologia , Inibidores da Enzima Conversora de Angiotensina/farmacologia , Animais , Doenças Cardiovasculares/tratamento farmacológico , Humanos , Renina/antagonistas & inibidoresRESUMO
Transgenic mice with cardiac-specific expression of a peptide inhibitor of G protein-coupled receptor kinase (GRK)3 [transgenic COOH-terminal GRK3 (GRK3ct) mice] display myocardial hypercontractility without hypertrophy and enhanced α(1)-adrenergic receptor signaling. A role for GRK3 in the pathogenesis of heart failure (HF) has not been investigated, but inhibition of its isozyme, GRK2, has been beneficial in several HF models. Here, we tested whether inhibition of GRK3 modulated evolving cardiac hypertrophy and dysfunction after pressure overload. Weight-matched male GRK3ct transgenic and nontransgenic littermate control (NLC) mice subjected to chronic pressure overload by abdominal aortic banding (AB) were compared with sham-operated (SH) mice. At 6 wk after AB, a significant increase of cardiac mass consistent with induction of hypertrophy was found, but no differences between GRK3ct-AB and NLC-AB mice were discerned. Simultaneous left ventricular (LV) pressure-volume analysis of electrically paced, ex vivo perfused working hearts revealed substantially reduced systolic and diastolic function in NLC-AB mice (n = 7), which was completely preserved in GRK3ct-AB mice (n = 7). An additional cohort was subjected to in vivo cardiac catheterization and LV pressure-volume analysis at 12 wk after AB. NLC-AB mice (n = 11) displayed elevated end-diastolic pressure (8.5 ± 3.1 vs. 2.9 ± 1.2 mmHg, P < 0.05), reduced cardiac output (3,448 ± 323 vs. 4,488 ± 342 µl/min, P < 0.05), and reduced dP/dt(max) and dP/dt(min) (both P < 0.05) compared with GRK3ct-AB mice (n = 16), corroborating the preserved cardiac structure and function observed in GRK3ct-AB hearts assessed ex vivo. Increased cardiac mass and myocardial mRNA expression of ß-myosin heavy chain confirmed the similar induction of cardiac hypertrophy in both AB groups, but only NLC-AB hearts displayed significantly elevated mRNA levels of brain natriuretic peptide and myocardial collagen contents as well as reduced ß(1)-adrenergic receptor responsiveness to isoproterenol, indicating increased LV wall stress and the transition to HF. Inhibition of cardiac GRK3 in mice does not alter the hypertrophic response but attenuates cardiac dysfunction and HF after chronic pressure overload.
Assuntos
Quinase 3 de Receptor Acoplado a Proteína G/fisiologia , Cardiopatias/tratamento farmacológico , Hipertensão/complicações , Miócitos Cardíacos/fisiologia , Adenilil Ciclases/metabolismo , Agonistas Adrenérgicos beta/farmacologia , Animais , Cardiomegalia/etiologia , Cardiomegalia/patologia , Fibrose Endomiocárdica/patologia , Quinase 3 de Receptor Acoplado a Proteína G/antagonistas & inibidores , Quinase 3 de Receptor Acoplado a Proteína G/genética , Cardiopatias/etiologia , Cardiopatias/fisiopatologia , Insuficiência Cardíaca/prevenção & controle , Imuno-Histoquímica , Isoproterenol/farmacologia , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Endogâmicos CBA , Miocárdio/enzimologia , Miocárdio/metabolismo , Miócitos Cardíacos/enzimologia , RNA Mensageiro/biossíntese , RNA Mensageiro/genética , Função Ventricular Esquerda/fisiologiaRESUMO
CCN2/connective tissue growth factor (CTGF), a CCN family matricellular protein repressed in healthy hearts after birth, is induced in heart failure of various etiologies. Multiple cellular and biological functions have been assigned to CCN2/CTGF depending on cellular context. However, the functions and mechanisms of action of CCN2/CTGF in the heart as well as its roles in cardiac physiology and pathophysiology remain unknown. Transgenic mice with cardiac-restricted overexpression of CTGF (Tg-CTGF) were generated and compared with nontransgenic littermate control (NLC) mice. Tg-CTGF mice displayed slightly lower cardiac mass and inconspicuous increase of myocardial collagen compared with NLC mice but no evidence of contractile dysfunction. Analysis of the myocardial transcriptome by DNA microarray revealed activation of several distinct gene programs in Tg-CTGF hearts involved in cardioprotection and growth inhibition. Indeed, Tg-CTGF mice subjected to ischemia-reperfusion injury by in situ transient occlusion of the left anterior descending coronary artery in vivo displayed reduced vulnerability with markedly diminished infarct size. These findings were recapitulated in isolated hearts perfused with recombinant human (h)CTGF before the ischemia-reperfusion procedure. Consistently, Tg-CTGF hearts, as well as isolated adult cardiac myocytes exposed to recombinant hCTGF, displayed enhanced phosphorylation and activity of the Akt/p70S6 kinase/GSK-3ß salvage kinase pathway and induction of several genes with reported cardioprotective functions. Inhibition of Akt activities also prevented the cardioprotective phenotype of hearts from Tg-CTGF mice. This report provides novel evidence that CTGF confers cardioprotection by salvage phosphokinase signaling leading to inhibition of GSK-3ß activities, activation of phospho-SMAD2, and reprogramming of gene expression.
Assuntos
Fator de Crescimento do Tecido Conjuntivo/farmacologia , Traumatismo por Reperfusão Miocárdica/metabolismo , Traumatismo por Reperfusão Miocárdica/fisiopatologia , Animais , Cardiotônicos/farmacologia , Células Cultivadas , Fator de Crescimento do Tecido Conjuntivo/genética , Perfilação da Expressão Gênica , Quinase 3 da Glicogênio Sintase/metabolismo , Glicogênio Sintase Quinase 3 beta , Humanos , Masculino , Camundongos , Camundongos Transgênicos , Infarto do Miocárdio/metabolismo , Traumatismo por Reperfusão Miocárdica/tratamento farmacológico , Traumatismo por Reperfusão Miocárdica/genética , Miócitos Cardíacos/efeitos dos fármacos , Miócitos Cardíacos/metabolismo , Miócitos Cardíacos/fisiologia , Fosforilação , Proteínas Proto-Oncogênicas c-akt/metabolismo , Proteínas Quinases S6 Ribossômicas 70-kDa/metabolismo , Proteína Smad2/metabolismoRESUMO
In this article, we report on a patient with chronic and modestly elevated plasma troponin T (TnT) levels and frequent hospitalizations following the first admission until his death one year later. The patient was initially admitted for dyspnea and discharged from hospital with a diagnosis of non-ST elevation acute myocardial infarction (AMI). Coronary angiography and echocardiography were normal, but the patient received the (false) diagnosis of AMI at two further admissions, based purely on elevated TnT. Shortly thereafter, severe respiratory failure with restrictive-type spirometry pattern became the predominant clinical symptom, with constantly elevated TnT levels at frequent re-admissions. Due to inconsistent follow-up by primarily junior and non-specialist staff at a number of different wards, pulmonary function tests and previous smoking history were mis-interpreted as typical of chronic obstructive pulmonary disease (COPD). The patient received standard COPD treatment without any improvement. After a year of gradually worsening respiratory failure and repeated hospitalizations, thorough assessment by a pulmonologist and neurologist established the final diagnosis of amyotrophic lateral sclerosis (ALS). The patient died shortly thereafter. While progressive respiratory failure is well-known to determine morbidity and mortality in patients with ALS, chronically elevated TnT levels in the absence of coronary artery disease have, to our best knowledge, not been described so far. We suggest that chronic myocardial hypoxia due to ALS-related hypoxic respiratory failure was the most likely underlying etiology for the elevated TnT levels seen here but other mechanism such as immune-mediated myocardial injury cannot be excluded.
Assuntos
Esclerose Lateral Amiotrófica/sangue , Esclerose Lateral Amiotrófica/diagnóstico , Erros de Diagnóstico , Troponina T/sangue , Idoso , Esclerose Lateral Amiotrófica/complicações , Biomarcadores , Hipóxia Celular , Doença das Coronárias/diagnóstico , Progressão da Doença , Dispneia/etiologia , Evolução Fatal , Seguimentos , Humanos , Hipóxia/etiologia , Hipóxia/patologia , Masculino , Infarto do Miocárdio/diagnóstico , Miocárdio/imunologia , Miocárdio/metabolismo , Miocárdio/patologia , Doença Pulmonar Obstrutiva Crônica/diagnóstico , Insuficiência Respiratória/etiologiaRESUMO
BACKGROUND: Thyroid storm is a life-threatening condition. Refractory cardiogenic shock and cardiac arrest are rare complications of thyroid storm and the treatment options are limited. CASE SUMMARY: A 35-year- old woman treated for Grave's disease was admitted with thyrotoxicosis complicated by infection and neutropenia caused by thionamide treatment. After treatment including beta-blockers, steroids, and Lugol's iodine solution, she went into cardiac arrest. Echocardiography after resuscitation demonstrated severe biventricular heart failure. The patient was in refractory cardiogenic shock with recurrent cardiac arrest and mechanical circulatory support with a veno-arterial extra corporal membrane oxygenation (V-A ECMO) circuit was established. After 2 days on V-A ECMO and supportive treatment with iodine solution, glucocorticosteroids, and levosimendan, her myocardial function recovered and thyroid hormone levels were normalized. Veno-arterial extra corporal membrane oxygenation was discontinued, and the patient was treated with early total thyroidectomy. The patient made a full recovery with no neurological/cognitive impairment, as assessed after 4 weeks. DISCUSSION: Adverse reactions to standard treatment of hyperthyroidism contributed to this patient's development of thyroid storm and the following refractory cardiogenic shock. When she was critically unstable, levosimendan improved myocardial function while inotropic support with dobutamine was ineffective, likely due to prolonged beta-antagonist administration. Temporary support with V-A ECMO, until effective lowering of thyroid hormone levels and improvement in myocardial function were obtained, was life-saving in this young patient and may be considered in refractory cardiogenic shock caused by thyroid storm.
RESUMO
Hypertension constitutes a major risk factor for heart failure with preserved ejection fraction (HFpEF). HFpEF is a prevalent clinical syndrome with increased cardiovascular morbidity and mortality. Specific guideline-directed medical therapy (GDMT) for HFpEF is not established due to lack of positive outcome data from randomized controlled trials (RCTs) and limitations of available studies. Although available evidence is limited, control of blood pressure (BP) is widely regarded as central to the prevention and clinical care in HFpEF. Thus, in current guidelines including the 2018 European Society of Cardiology (ESC) and European Society of Hypertension (ESH) Guidelines, blockade of the renin-angiotensin system (RAS) with either angiotensin-converting enzyme inhibitors or angiotensin receptor blockers provides the backbone of BP-lowering therapy in hypertensive patients. Although superiority of RAS blockers has not been clearly shown in dedicated RCTs designed for HFpEF, we propose that this core drug treatment strategy is also applicable for hypertensive patients with HFpEF with the addition of some modifications. The latter apply to the use of spironolactone apart from the treatment of resistant hypertension and the use of the angiotensin receptor neprilysin inhibitor. In addition, novel agents such as sodium-glucose co-transporter-2 inhibitors, currently already indicated for high-risk patients with diabetes to reduce heart failure hospitalizations, and finerenone represent promising therapies and results from ongoing RCTs are eagerly awaited. The development of an effective and practical classification of HFpEF phenotypes and GDMT through dedicated high-quality RCTs are major unmet needs in hypertension research and calls for action.
Assuntos
Insuficiência Cardíaca , Hipertensão , Antagonistas de Receptores de Angiotensina/uso terapêutico , Inibidores da Enzima Conversora de Angiotensina , Insuficiência Cardíaca/tratamento farmacológico , Humanos , Hipertensão/tratamento farmacológico , Volume SistólicoRESUMO
Adrenomedullin (AM) is a potent vasorelaxing peptide with natriuretic, diuretic, and growth inhibitory properties. Plasma concentrations and myocardial AM expression are increased in heart failure (HF). Since AM and AM binding sites are abundantly expressed in the lungs, we investigated to what extent pulmonary AM and AM receptor subtypes [CRLR/RAMP2 (AM1) and CRLR/RAMP3 (AM2)] are changed in HF and whether the lungs contribute to the increased plasma concentrations of AM reported in HF. Pulmonary AM mRNA and protein expression were increased by 2.8- and 2.6-fold, respectively, whereas mRNA expression of RAMP2 and CRLR was decreased in rats with HF 7 days after induction of MI compared to sham-operated rats (P < 0.05). Pulmonary AM receptor density was substantially decreased in HF rats compared to sham (3.7 +/-0.6 vs. 29.9 +/- 1.1 fmol/mg membrane protein; P < 0.05). Immunoreactivities against AM and the AM receptor components CRLR, RAMP2, and RAMP3 in the pulmonary tissue were seen in vascular smooth muscle cells, vascular endothelial cells, and in alveolar macrophages. AM mRNA expression in alveolar macrophages obtained from HF rats by bronchoalveolar lavage was 2.9-fold higher than in sham-operated rats (P < 0.05). An even more substantial increase of AM mRNA expression was found in alveolar macrophages from patients with HF (10-fold, P < 0.05), and this increase displayed a negative correlation to left ventricular systolic function (P < 0.05). Furthermore, a net release of AM from the lungs into the circulation was only found in HF patients with the most severe left ventricular systolic dysfunction. Thus, our data demonstrate increased expression and decreased receptor binding of AM in the lungs in severe HF. Furthermore, our data indicate that alveolar macrophages are an important source of pulmonary AM in both experimental and clinical HF. Finally, a net release of AM from the lungs into the circulation was only found in patients with severe systolic dysfunction.
Assuntos
Adrenomedulina/metabolismo , Insuficiência Cardíaca/metabolismo , Pulmão/metabolismo , Macrófagos Alveolares/metabolismo , Receptores de Peptídeos/metabolismo , Animais , Sítios de Ligação , Pressão Sanguínea , Proteína Semelhante a Receptor de Calcitonina , Expressão Gênica , Insuficiência Cardíaca/imunologia , Insuficiência Cardíaca/fisiopatologia , Humanos , Imuno-Histoquímica , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Pulmão/patologia , Masculino , Proteínas de Membrana/metabolismo , Infarto do Miocárdio/metabolismo , Infarto do Miocárdio/fisiopatologia , Miocárdio/patologia , Tamanho do Órgão , RNA Mensageiro/metabolismo , Ratos , Ratos Wistar , Proteína 2 Modificadora da Atividade de Receptores , Proteína 3 Modificadora da Atividade de Receptores , Proteínas Modificadoras da Atividade de Receptores , Receptores de Adrenomedulina , Receptores da Calcitonina/metabolismo , Sístole , Função Ventricular EsquerdaRESUMO
In ischemic congestive heart failure (CHF), anemia is associated with poor prognosis. Whether anemia develops in nonischemic CHF is uncertain. The hematopoietic inhibitors TNF-alpha and nitric oxide (NO) are activated in ischemic CHF. We examined whether mice with ischemic or nonischemic CHF develop anemia and whether TNF-alpha and NO are involved. We studied mice (n = 7-9 per group) with CHF either due to myocardial infarction (MI) or to overexpression of the Ca(2+)-binding protein calsequestrin (CSQ) or to induced cardiac disruption of the sarcoplasmic reticulum Ca(2+)-ATPase 2 gene (SERCA2 KO). Hematopoiesis was analyzed by colony formation of CD34(+) bone marrow cells. Hemoglobin concentration was 14.0 +/- 0.4 g/dl (mean +/- SD) in controls, while it was decreased to 10.1 +/- 0.4, 9.7 +/- 0.4, and 9.6 +/- 0.3 g/dl in MI, CSQ, and SERCA2 KO, respectively (P < 0.05). Colony numbers per 100,000 CD34(+) cells in the three CHF groups were reduced to 33 +/- 3 (MI), 34 +/- 3 (CSQ), and 39 +/- 3 (SERCA2 KO) compared with 68 +/- 4 in controls (P < 0.05). Plasma TNF-alpha nearly doubled in MI, and addition of anti-TNF-alpha antibody normalized colony formation. Inhibition of colony formation was completely abolished with blockade of endothelial NO synthase in CSQ and SERCA2 KO, but not in MI. In conclusion, the mechanism of anemia in CHF depends on the etiology of cardiac disease; whereas TNF-alpha impairs hematopoiesis in CHF following MI, NO inhibits blood cell formation in nonischemic murine CHF.