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We present the case of a 47-year-old man with a history of recurrent episodes of frontal headache, fever, and chest discomfort as well as longstanding, difficult to treat arterial hypertension. Clinical work-up revealed the unexpected finding of an underlying pheochromocytoma as well as recent "silent" myocardial infarction. Our case highlights the importance of paying attention to incidental cardiac findings on somatostatin receptor positron emission tomography/computed tomography, as routinely performed in patients with clinically suspected neuroendocrine tumors. These incidental cardiac findings cannot only indicate a primary or secondary (metastatic) neuroendocrine tumor, but also areas of myocardial inflammation, as somatostatin receptors cannot only be found on the majority of neuroendocrine tumors, but also among other tissues on the surface of activated macrophages and lymphocytes. The detection of myocardial inflammation is of clinical importance and its underlying etiology should be evaluated to prompt eventual necessary treatment, as it is a potential driving force for cardiac remodeling and poor prognosis.
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Tumores Neuroendócrinos , Compostos Organometálicos , Humanos , Inflamação , Masculino , Pessoa de Meia-Idade , Octreotida , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/métodos , Tomografia por Emissão de Pósitrons/métodos , Compostos Radiofarmacêuticos , Receptores de SomatostatinaRESUMO
BACKGROUND: Cardiac sarcoidosis (CS) and giant cell myocarditis (GCM) are rare diseases that share some similarities, but also display different clinical and histopathological features. We aimed to compare the demographics, clinical presentation, and outcome of patients diagnosed with CS or GCM. METHOD: We compared the clinical data and outcome of all adult patients with CS (n = 71) or GCM (n = 21) diagnosed at our center between 1991 and 2020. RESULTS: The median (interquartile range) follow-up time for patients with CS and GCM was 33.5 [6.5-60.9] and 2.98 [0.6-40.9] months, respectively. In the entire cohort, heart failure (HF) was the most common presenting manifestation (31%), followed by ventricular arrhythmias (25%). At presentation, a left ventricular ejection fraction of < 50% was found in 54% of the CS compared to 86% of the GCM patients (P = 0.014), while corresponding proportions for right ventricular dysfunction were 24% and 52% (P = 0.026), respectively. Advanced HF (NYHA ≥ IIIB) was less common in CS (31%) than in GCM (76%). CS patients displayed significantly lower circulating levels of natriuretic peptides (P < 0.001) and troponins (P = 0.014). Eighteen percent of patients with CS included in the survival analysis reached the composite endpoint of death or heart transplantation (HTx) compared to 68% of patients with GCM (P < 0.001). CONCLUSION: GCM has a more fulminant clinical course than CS with severe biventricular failure, higher levels of circulating biomarkers and an increased need for HTx. The histopathologic diagnosis remained key determinant even after adjustment for markers of cardiac dysfunction.
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Miocardite , Sarcoidose , Adulto , Células Gigantes/patologia , Humanos , Miocardite/diagnóstico , Miocardite/patologia , Miocardite/terapia , Sarcoidose/diagnóstico , Sarcoidose/epidemiologia , Sarcoidose/terapia , Volume Sistólico , Suécia/epidemiologia , Função Ventricular EsquerdaRESUMO
PURPOSE: Recognition of congestion and hypoperfusion in patients with chronic left ventricular dysfunction (LVD) has therapeutic and prognostic implications. In the present study we hypothesized that a multiparameter echocardiographic grading of right ventricular dysfunction (RVD) can facilitate the characterization of hemodynamic profiles. METHODS: Consecutive patients (n = 105, age 53 ± 14 years, males 77%, LV ejection fraction 28 ± 11%) referred for heart transplant or heart failure work-up, with catheterization and echocardiography within 48 h, were reviewed retrospectively. Three hemodynamic profiles were defined: compensated LVD (cLVD, normal pulmonary capillary wedge pressure (PCWP < 15 mmHg) and normal mixed venous saturation (SvO2 ≥ 60%)); decompensated LVD (dLVD, with increased PCWP) and LV failure (LVF, increased PCWP and reduced SvO2). We established a 5-point RVD score including pulmonary hypertension, reduced tricuspid annular plane systolic excursion, RV dilatation, ≥ moderate tricuspid regurgitation and increased right atrial pressure. RESULTS: The RVD score [median (IQR 25%;75%)] showed significant in-between the three groups differences with 1 (0;1), 1 (0.5;2) and 3.0 (2;3.5) in patients with cLVD, dLVD and LVF, respectively. The finding of RVD score ≥ 2 or ≥ 4 increased the likelihood of decompensation or LVF 5.2-fold and 6.7-fold, respectively. On the contrary, RVD score < 1 and < 2 reduced the likelihood 11.1-fold and 25-fold, respectively. The RVD score was more helpful than standard echocardiography regarding identification of hemodynamic profiles. CONCLUSIONS: In this proof of concept study an echocardiographic RVD score identified different hemodynamic severity profiles in patients with chronic LVD and reduced ejection fraction. Further studies are needed to validate its general applicability.
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Insuficiência Cardíaca , Disfunção Ventricular Esquerda , Disfunção Ventricular Direita , Adulto , Idoso , Ecocardiografia , Insuficiência Cardíaca/diagnóstico , Hemodinâmica , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Volume Sistólico , Disfunção Ventricular Esquerda/diagnóstico por imagem , Disfunção Ventricular Esquerda/etiologia , Disfunção Ventricular Direita/diagnóstico por imagem , Disfunção Ventricular Direita/etiologia , Função Ventricular DireitaRESUMO
AIMS: Cardiac injury and remodelling are associated with the rearrangement of cardiac lipids. Glycosphingolipids are membrane lipids that are important for cellular structure and function, and cardiac dysfunction is a characteristic of rare monogenic diseases with defects in glycosphingolipid synthesis and turnover. However, it is not known how cardiac glycosphingolipids regulate cellular processes in the heart. The aim of this study is to determine the role of cardiac glycosphingolipids in heart function. METHODS AND RESULTS: Using human myocardial biopsies, we showed that the glycosphingolipids glucosylceramide and lactosylceramide are present at very low levels in non-ischaemic human heart with normal function and are elevated during remodelling. Similar results were observed in mouse models of cardiac remodelling. We also generated mice with cardiomyocyte-specific deficiency in Ugcg, the gene encoding glucosylceramide synthase (hUgcg-/- mice). In 9- to 10-week-old hUgcg-/- mice, contractile capacity in response to dobutamine stress was reduced. Older hUgcg-/- mice developed severe heart failure and left ventricular dilatation even under baseline conditions and died prematurely. Using RNA-seq and cell culture models, we showed defective endolysosomal retrograde trafficking and autophagy in Ugcg-deficient cardiomyocytes. We also showed that responsiveness to ß-adrenergic stimulation was reduced in cardiomyocytes from hUgcg-/- mice and that Ugcg knockdown suppressed the internalization and trafficking of ß1-adrenergic receptors. CONCLUSIONS: Our findings suggest that cardiac glycosphingolipids are required to maintain ß-adrenergic signalling and contractile capacity in cardiomyocytes and to preserve normal heart function.
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Glucosiltransferases , Miócitos Cardíacos , Animais , Cardiomegalia , Glucosiltransferases/genética , Camundongos , Receptores AdrenérgicosRESUMO
BACKGROUND: Temporal trends in clinical composition and outcome in dilated cardiomyopathy (DCM) are largely unknown, despite considerable advances in heart failure management. We set out to study clinical characteristics and prognosis over time in DCM in Sweden during 2003-2015. METHODS: DCM patients (n = 7873) from the Swedish Heart Failure Registry were divided into three calendar periods of inclusion, 2003-2007 (Period 1, n = 2029), 2008-2011 (Period 2, n = 3363), 2012-2015 (Period 3, n = 2481). The primary outcome was the composite of all-cause death, transplantation and hospitalization during 1 year after inclusion into the registry. RESULTS: Over the three calendar periods patients were older (p = 0.022), the proportion of females increased (mean 22.5%, 26.4%, 27.6%, p = 0.0001), left ventricular ejection fraction was higher (p = 0.0014), and symptoms by New York Heart Association less severe (p < 0.0001). Device (implantable cardioverter defibrillator and/or cardiac resynchronization) therapy increased by 30% over time (mean 11.6%, 12.3%, 15.1%, p < 0.0001). The event rates for mortality, and hospitalization were consistently decreasing over calendar periods (p < 0.0001 for all), whereas transplantation rate was stable. More advanced physical symptoms correlated with an increased risk of a composite outcome over time (p = 0.0043). CONCLUSIONS: From 2003 until 2015, we observed declining mortality and hospitalizations in DCM, paralleled by a continuous change in both demographic profile and therapy in the DCM population in Sweden, towards a less affected phenotype.
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Terapia de Ressincronização Cardíaca/tendências , Cardiomiopatia Dilatada/terapia , Fármacos Cardiovasculares/uso terapêutico , Cardioversão Elétrica/tendências , Transplante de Coração/tendências , Hospitalização/tendências , Idoso , Terapia de Ressincronização Cardíaca/efeitos adversos , Terapia de Ressincronização Cardíaca/mortalidade , Cardiomiopatia Dilatada/diagnóstico , Cardiomiopatia Dilatada/mortalidade , Cardiomiopatia Dilatada/fisiopatologia , Fármacos Cardiovasculares/efeitos adversos , Causas de Morte/tendências , Progressão da Doença , Cardioversão Elétrica/efeitos adversos , Cardioversão Elétrica/mortalidade , Feminino , Transplante de Coração/efeitos adversos , Transplante de Coração/mortalidade , Humanos , Masculino , Pessoa de Meia-Idade , Fenótipo , Prognóstico , Sistema de Registros , Fatores de Risco , Suécia , Fatores de TempoRESUMO
Heart transplantation (HTx) for patients with "giant cell myocarditis" (GCM) or "cardiac sarcoidosis" (CS) is still controversial. However, no single center has accumulated enough experience to investigate post-HTx outcome. The primary aim of this systematic review is to identify, appraise, and synthesize existing literature investigating whether patients who have undergone HTx because of GCM or CS have worse outcomes as compared with patients transplanted because of other etiologies. A systematic and comprehensive search will be performed using PubMed, Scopus, Web of Science, EMBASE, and Google Scholar, for studies published up to December 2019. Observational and interventional population-based studies will be eligible for inclusion. The quality of observational studies will be assessed using the Newcastle-Ottawa scale, while the interventional studies will be assessed using the Cochrane Effective Practice Organization of Care tool. The collected evidence will be narratively synthesized; in addition, we will perform a meta-analysis to pool estimates from studies considered to be homogenous. Reporting of the systematic review and meta-analysis will be in accordance with the Meta-analysis of Observational Studies in Epidemiology Preferred Reporting Items for Systematic reviews and Meta-Analysis guidelines. To our knowledge, this will be the first synthesis of outcomes, including survival, acute cellular rejection, and disease recurrence, in patients with either GCM or CS treated with HTx. Reviewing the suitability of HTx in this population and highlighting areas for further research will benefit both patients and healthcare providers. Trial registration: CRD42019140574.
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Rejeição de Enxerto/epidemiologia , Transplante de Coração/métodos , Miocardite/cirurgia , Seguimentos , Saúde Global , Humanos , Incidência , Fatores de Risco , Fatores de TempoRESUMO
BACKGROUND: Parvovirus B19 (PVB19) has emerged as one of the viruses possibly inducing chronic myocarditis and subsequent idiopathic dilated cardiomyopathy (IDCM). The aim of this work was to investigate the presence and long-term consequences of PVB19-DNA within myocardial biopsies from patients with IDCM and to compare the findings with those from donor hearts (control group). METHODS AND RESULTS: Forty hospitalized IDCM patients (age 47 ± 12 y) with mean left ventricular ejection fraction 27 ± 12% were included. The presence of PVB19-DNA in myocardial biopsies and of IgG and IgM antibodies in patient sera was analyzed. The control group consisted of 20 donor hearts. The follow-up time was 112 ± 57 months. PVB19-DNA was found in myocardial biopsies of both patients (73%) and control samples (55%; Pâ¯=â¯.25).Three deaths and 8 heart transplantations occurred in the IDCM group, and 6 deaths in the control group (ie, the recipients of the control hearts). No difference in transplantation-free survival between the PVB19-DNA positive/negative IDCM patients or transplant recipients was found. CONCLUSIONS: PVB19-DNA is a common finding in both patients with IDCM and in healthy donor hearts, not affecting prognosis. These findings support the view that PVB19 is an innocent bystander, frequently found in myocardium with low DNA copies, and not a plausible cause of IDCM.
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Cardiomiopatia Dilatada/patologia , Cardiomiopatia Dilatada/virologia , Endocárdio/patologia , Endocárdio/virologia , Miocárdio/patologia , Parvovirus B19 Humano/isolamento & purificação , Adulto , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Estudos ProspectivosRESUMO
OBJECTIVES: To quantify healthcare resource use (HRU) and costs in relation to carcinoid syndrome (CS) and carcinoid heart disease (CHD) in a real-world setting, and to provide perspective on treatment patterns. MATERIALS AND METHODS: Patient data and HRU were collected retrospectively from three Swedish healthcare registers. Adult patients diagnosed with metastatic gastroenteropancreatic neuroendocrine tumors (GEP-NETs) grade 1 or 2 and CS who purchased somatostatin analogs (SSAs), and experienced controlled (defined by SSAs use) and uncontrolled (defined by SSAs dose escalation) CS for ≥8 months during the study period were included. Patients diagnosed with CHD from the date of the GEP-NET diagnosis were included in the CHD study group. RESULTS: Overall, total HRU cost increased with uncontrolled CS and CHD. Total resource cost was 15,500/patient during controlled CS (8 months), rising to 21,700/patient during uncontrolled CS (8 months), representing an increase of â¼40% (6200/patient). Costs/patient were driven mainly by SSA use, tumor-related medical interventions and examinations. The total mean cost/year of disease was 1100/patient without CHD, compared to 4600/patient with CHD, a difference of 3500/patient. Excluding SSA cost burden, the main drivers of increased cost in CHD patients were surgical interventions and echocardiography. CONCLUSIONS: This study provides a comprehensive overview of the treatment patterns and burden of uncontrolled CS symptoms and CHD using Swedish national register data. Increases in medical interventions and examinations HRU and increased SSA use suggest that SSA dose escalation alone may not effectively control the symptoms associated with uncontrolled CS, highlighting an unmet treatment need in this patient group.
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Doença Cardíaca Carcinoide/economia , Doença Cardíaca Carcinoide/terapia , Neoplasias Intestinais/complicações , Síndrome do Carcinoide Maligno/economia , Síndrome do Carcinoide Maligno/terapia , Tumores Neuroendócrinos/complicações , Neoplasias Pancreáticas/complicações , Antagonistas da Serotonina/economia , Neoplasias Gástricas/complicações , Idoso , Doença Cardíaca Carcinoide/diagnóstico , Custos e Análise de Custo , Feminino , Custos de Cuidados de Saúde , Humanos , Masculino , Síndrome do Carcinoide Maligno/diagnóstico , Pessoa de Meia-Idade , Sistema de Registros , Estudos Retrospectivos , Antagonistas da Serotonina/uso terapêutico , SuéciaRESUMO
AIMS: The pathophysiology of heart failure with preserved ejection fraction (HFPEF) is not fully understood. A recently proposed mechanism for HFPEF is that it is a systemic pro-inflammatory state induced by comorbidities, leading to microvascular endothelial dysfunction and subsequent cardiac remodeling and dysfunction. We hypothesize that targeting comorbidities will improve outcomes in elderly patients with HFPEF. Thus, the aim of this study is to determine whether the combination of systematic screening and optimal management of prespecified comorbidities associated with HFPEF improves outcomes. METHODS: This multicenter, prospective, randomized intervention trial uses an open procedure with blinded endpoint assessment. Patients with HFPEF aged >60 years (n = 360) will be randomized 1:1 to the usual care or intervention arm of the trial. When randomized to the intervention arm, all patients will be systematically screened and optimally treated for the most frequent cardiovascular, metabolic, respiratory, and renal comorbidities. The primary endpoint is a composite clinical score that classifies each randomized patient as improved or deteriorated based on objective and subjective data at a 24-month follow-up performed by a blinded endpoint committee. CONCLUSION: Rather than targeting cardiac dysfunction, our study aims to present evidence for a possible paradigm shift in the management of HFPEF. Our novel concept focuses on the management of comorbidities as predisposing factors in HFPEF.
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Doença Crônica/terapia , Insuficiência Cardíaca/terapia , Idoso , Comorbidade , Insuficiência Cardíaca/fisiopatologia , Humanos , Estudos Prospectivos , Volume SistólicoRESUMO
AIMS: Risk stratification of patients with new-onset acute heart failure (AHF) is important but remains challenging. In the present study, we evaluated the prognostic value of a new multiparameter right ventricular dysfunction (RVD) score. METHODS AND RESULTS: Patients (n = 210) hospitalized due to new-onset AHF between 2015 and 2018 were retrospectively included. Mean age was 56 ± 10 years, 24% were female and median left ventricular ejection fraction was 28% (interquartile range 20; 34%). The RVD score, tricuspid annular plane systolic excursion (TAPSE), and fractional area change (FAC) were determined at index hospitalization and after therapy titration. The 4-point RVD score included reduced TAPSE, right ventricular enlargement, moderate or severe tricuspid regurgitation and increased central venous pressure. The study endpoint was a composite of all-cause mortality, left ventricular assist device implantation, and heart transplantation. After 60 months median follow-up time, 53 (25%) patients met the endpoint. At index hospitalization, there were no significant differences in any echocardiographic parameter between patients with and without the endpoint. After therapy titration, there were differences in TAPSE (16 vs. 19 mm, P = 0.001), FAC (33 vs. 40%, P < 0.001) and the proportion of patients with RVD score ≥2 (36 vs. 4%, P < 0.001). The presence of RVD despite therapy titration had different impact on survival depending on the parameter considered: the proportion of patients free from events after 1 year was 87% in patients with TAPSE <17 mm, 89% in patients with FAC <35% and 65% in patients with RVD score ≥2. In a multivariable analysis, RVD score ≥2 after therapy titration, but not TAPSE <17 mm or FAC < 35%, remained associated with a higher risk of the composite endpoint (hazard ratio 3.11, 95% confidence interval 1.44-6.74). CONCLUSIONS: A novel multiparametric RVD score might improve prognostic stratification in patients with new-onset AHF. RVD after therapy titration, but not at index hospitalization is associated with a higher risk of the composite endpoint.
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It is still debated whether arterial elasticity provides prognostic information for cardiovascular risk beyond blood pressure measurements in a healthy population. To investigate the association between arterial elasticity obtained by radial artery pulse wave analysis and risk for cardiovascular diseases (CVD) in men and women. In 2002-2005, 2362 individuals (men=1186, 50.2%) not taking antihypertensive medication were included. C2 (small artery elasticity) was measured using the HDI/Pulse Wave CR2000. Data on acute myocardial infarction or stroke, fatal or non-fatal, was obtained between 2002-2019. Cox- regression was used to investigate associations between C2 and future CVD, adjusting for confounding factors such as age, sex, systolic blood pressure, heart rate, HOMA-IR (Homeostatic Model Assessment for Insulin Resistance), LDL- cholesterol, CRP (C-Reactive Protein), alcohol consumption, smoking and physical activity. At baseline, the mean age of 46 ± 10.6 years and over the follow-up period, we observed 108 events 70 events in men [event rate: 5.9%], 38 in women [event rate: 3.2%]. In the fully adjusted model, and for each quartile decrease in C2, there was a significant increase in the risk for incident CVD by 36%. (HR = 1.36, 95% CI: 1.01-1.82, p = 0.041). The results were accentuated for all men (HR = 1.74, 95% CI: 1.21-2.50, p = 0.003) and women over the age of 50 years (HR = 1.70, 95% CI: 0.69-4.20). We showed a strong and independent association between C2 and CVD in men. In women after menopause, similar tendencies and effect sizes were observed.
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Doenças Cardiovasculares , Infarto do Miocárdio , Masculino , Humanos , Feminino , Adulto , Pessoa de Meia-Idade , Estudos Longitudinais , Fatores de Risco , Doenças Cardiovasculares/diagnóstico , Doenças Cardiovasculares/epidemiologia , Infarto do Miocárdio/epidemiologia , Elasticidade , Progressão da Doença , Artéria RadialRESUMO
BACKGROUND: Early substitution of calcineurin inhibitor (CNI) with mammalian target of rapamycin inhibitors has been shown to improve kidney function and reduce intimal hyperplasia in heart transplant (HTx) recipients but data on long-term outcome of such a regime are still sparse. METHODS: In the SCHEDULE trial, 115 de novo HTx recipients were randomized to (1) everolimus with reduced exposure of CNI followed by CNI withdrawal at week 7-11 post-transplant or (2) standard-exposure with CNI. Both groups received mycophenolate mofetil and corticosteroids. Herein we report on the 10-12-year long-term follow-up of the study. RESULTS: A total of 78 patients attended the follow-up visit at a median time of 11 years post-transplant. In the everolimus intention to treat (ITT) group 87.5% (35/40 patients) still received everolimus and in the CNI ITT group 86.8% (33/38) still received CNI. Estimated glomerular filtration rate (eGFR) (least square mean (95% CI)) at the 10-12 years visit was 82.7 (74.2-91.1) ml/min/1.73 m2 and 61.0 (52.3-69.7) ml/min/1.73 m2 in the everolimus and CNI group, respectively (p < 0.001). Graft function measured by ejection fraction, ECG, NT-proBNP and drug safety were comparable between groups. During the study period there was a total of 28 deaths, but there was no difference in survival between the everolimus and the CNI group (aHR 0.61 (95% CI 0.29-1.30) p = 0.20). For the composite endpoint of death, re-transplantation, myocardial infarction, PCI, dialysis, kidney transplantation or cancer no between group differences were found (aHR 1.0 (95% CI 0.57-1.77) p = 0.99). CONCLUSIONS: De novo HTx patients randomized to everolimus and low dose CNI followed by CNI free therapy sustained significantly better long-term kidney function than patients randomized to standard therapy. The graft function at 10-12 years was similar in both groups and there was no difference in survival.
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AIMS: In heart failure (HF) with reduced left ventricular ejection fraction (HFrEF), the prognosis appears better in non-ischaemic than in ischaemic aetiology. Infrequent diagnostic work-up for ischaemic heart disease (IHD) in HF is reported. In this study, we compared short-term response to initiated guideline-directed medical treatment (GDMT) in recent-onset HFrEF of non-ischaemic (non-IHF) vs. ischaemic (IHF) aetiology and evaluated the frequency of coronary investigation. METHODS AND RESULTS: Patients hospitalized with recent-onset HFrEF [left ventricular ejection fraction (LVEF) < 40%] between 1 January 2016 and 31 December 2019 were included. Treatment response was determined by use of a hierarchical clinical composite outcome classifying each patient as worsened, improved, or unchanged based on hard outcomes (mortality, heart transplantation, and HF hospitalization) and soft outcomes (± ≥10 unit change in LVEF, ± ≥30% change in N-terminal pro-B-type natriuretic peptide, and ± ≥1 point change in New York Heart Association functional class) during 28 weeks of follow-up. The associations between baseline characteristics and composite changes were analysed with multiple logistic regression. Among the 364 patients analysed, 47 were not investigated for IHD. Comparing non-IHF (n = 203) vs. IHF (n = 114), patients were younger (mean age 61.0 vs. 69.4 years, P < 0.001) with lower mean LVEF (26% vs. 31%, P < 0.001), but with similar male predominance (70.4% vs. 75.4%, P = 0.363). For non-IHF vs. IHF, the composite outcomes were worsened (19.1% vs. 43.9%, P < 0.001) and improved (74.2% vs. 43.9%, P < 0.001). After multivariable adjustments, IHF was associated with increased odds for worsening [odds ratio (OR) 2.94; 95% confidence interval (CI) 1.51-5.74; P = 0.002] and decreased odds for improvement (OR 0.35; 95% CI 0.18-0.65; P < 0.001). In cases without previous IHD or new-onset myocardial infarction (n = 261), a decision for coronary investigation was made in 69.0%. CONCLUSIONS: In recent-onset HFrEF, patients with non-IHF responded better to GDMT than patients with IHF. Almost one-third of patients selected for follow-up at HF clinics were never investigated for IHD.
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Insuficiência Cardíaca , Transplante de Coração , Isquemia Miocárdica , Humanos , Masculino , Pessoa de Meia-Idade , Feminino , Volume Sistólico/fisiologia , Função Ventricular Esquerda/fisiologia , PrognósticoRESUMO
BACKGROUND: Pulmonary hypertension (PH) is frequent in patients with heart failure and reduced ejection fraction (HFrEF) with 2 different phenotypes: isolated postcapillary PH (IpcPH) and, with the worst prognosis, combined pre- and postcapillary PH (CpcPH). The aims of the present echocardiography study were to investigate (1) the ability to identify PH phenotype in patients with HFrEF using the newly adopted definition of PH (mean pulmonary artery pressure >20 mm Hg) and (2) the relationship between PH phenotype and right ventricular (RV) function. METHODS: One hundred twenty-four patients with HFrEF consecutively referred for heart transplant or heart failure workup were included with echocardiography and right heart catheterization within 48 hours. We estimated systolic pulmonary artery pressure (sPAPDoppler) and used a method to detect increased pulmonary vascular resistance (>3 Wood units) based on predefined thresholds of 3 pressure reflection (PRefl) variables (the acceleration time in the RV outflow tract [RVOT], the interval between peak RVOT and peak tricuspid regurgitant velocity, and the RV pressure augmentation following peak RVOT velocity). RESULTS: Using receiver operator characteristic analysis in a derivation group (n = 62), we identified sPAPDoppler ≥35 mm Hg as a cutoff that in a test group (n = 62) increased the likelihood of PH 6.6-fold. The presence of sPAPDoppler >40 mm Hg and 2 or 3 positive PRefl variables increased the probability of CpcPH 6- to 8-fold. A 2-step approach with primarily assessment of sPAPDoppler and the supportive use of PRefl variables in patients with mild/moderate PH (sPAPDoppler 41-59 mm Hg) showed 76% observer agreement and a weighted kappa of 0.63. The steady-state (pulmonary vascular resistance) and pulsatile (compliance, elastance) vascular loading are increased in both IpcPH and CpcPH with a comparable degree of RV dysfunction. CONCLUSIONS: The PH phenotype can be identified in HFrEF using standard echocardiographic assessment of pulmonary artery pressure with supportive use of PRefl variables in patients with mild to moderate PH.
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Insuficiência Cardíaca , Hipertensão Pulmonar , Disfunção Ventricular Esquerda , Humanos , Hipertensão Pulmonar/diagnóstico , Insuficiência Cardíaca/diagnóstico , Insuficiência Cardíaca/diagnóstico por imagem , Artéria Pulmonar/diagnóstico por imagem , Volume Sistólico , Ecocardiografia , FenótipoRESUMO
Background: Giant cell myocarditis (GCM) and cardiac sarcoidosis (CS) are, in contrast to acute non-fulminant myocarditis (ANFM), rare inflammatory diseases of the myocardium with poor prognosis. Although echocardiography is the first-line diagnostic tool in these patients, their echocardiographic appearance has so far not been systematically studied. Methods: We assessed a total of 71 patients with endomyocardial biopsy-proven GCM (n = 21), and CS (n = 25), as well as magnetic resonance-verified ANFM (n = 25). All echocardiographic examinations, performed upon clinical presentation, were reanalysed according to current guidelines including a detailed assessment of right ventricular (RV) dysfunction. Results: In comparison with ANFM, patients with either GCM or CS were older (mean age (±SD) 55 ± 12 or 53 ± 8 vs 25 ± 8 years), more often of female gender (52% or 24% vs 8%), had more severe clinical symptoms and higher natriuretic peptide levels. For both GCM and CS, echocardiography revealed more frequently signs of left ventricular (LV) dysfunction in form of a reduced ejection fraction (p < 0.001), decreased cardiac index (p < 0.001) and lower global longitudinal strain (p < 0.001) in contrast to ANFM. The most prominent increase in LV end-diastolic volume index was observed in CS. In addition, RV dysfunction was more frequently found in both GCM and CS than in ANFM (p = 0.042). Conclusions: Both GCM and CS have an echocardiographic and clinical appearance that is distinct from ANFM. However, the method cannot further differentiate between the two rare entities. Consequently, echocardiography can strengthen the initial clinical suspicion of a more severe form of myocarditis, thus warranting a more rigorous clinical work-up.
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BACKGROUND: Giant cell myocarditis (GCM) and cardiac sarcoidosis (CS) are rare inflammatory diseases of the myocardium with poor prognosis. Little is known about the cardiovascular magnetic resonance (CMR) appearance of GCM and the methods ability to distinguish the two rare entities from one another. METHODS: We assessed a total of 40 patients with endomyocardial biopsy-proven GCM (n = 14) and CS (n = 26) concerning their clinical and CMR appearance in a blinded manner. RESULTS: Patients with GCM and CS were of similar median age (55 vs 56 years), and a male predominance was observed in both groups. In GCM, median levels of troponin T (313 vs 31 ng/L, p < 0.001), and natriuretic peptides (6560 vs 676 pg/mL, p < 0.001) were higher than in CS, and the clinical outcome worse (p = 0.04). On CMR imaging, the observed alterations of left and right ventricular (LV/RV) dimensions and function were similar. GCM showed multifocal LV late gadolinium enhancement (LGE) with a similar longitudinal, circumferential, and radial distribution as in CS, including suggested signature imaging biomarkers of CS like the "hook sign" (71% vs 77%, p = 0.702). The median LV LGE enhanced volume was 17% and 22% in GCM and CS (p = 0.150), respectively. The number of RV segments with pathologically increased T2 signal and/or LGE were most extensive in GCM. CONCLUSIONS: The CMR appearance of both GCM and CS is highly similar, making the differentiation between the two rare entities solely based on CMR challenging. This stands in contrast to the clinical appearance, which seems to be more severe in GCM.
Assuntos
Miocardite , Sarcoidose , Humanos , Masculino , Pessoa de Meia-Idade , Feminino , Meios de Contraste , Imagem Cinética por Ressonância Magnética/métodos , Gadolínio , Imageamento por Ressonância Magnética/métodos , Sarcoidose/diagnóstico por imagem , Espectroscopia de Ressonância Magnética , Células Gigantes/patologia , Valor Preditivo dos TestesRESUMO
AIMS: Due to the shortage of heart donors, increasing numbers of heart transplantation (HTx) candidates are receiving long-term mechanical circulatory support (MCS) as bridge-to-transplantation. Treatment with MCS is associated with increased formation of anti-human leukocyte antigen antibodies (allosensitization), but whether this affects post-HTx outcomes is unclear. METHODS AND RESULTS: We included all adult patients who received long-term MCS as bridge-to-transplantation and underwent subsequent HTx at our centre between 2008 and 2018. We also enrolled medically treated HTx recipients without prior MCS as controls. These controls were matched by age, sex, diagnosis, and transplantation era. Outcome parameters were compared between the two study groups. A total of 126 patients (48 ± 15 years, 84% male) were included of whom 64 were bridged with MCS and 62 were matched controls. Pre-HTx allosensitization occurred more frequently in the MCS group than in the control group (27% vs. 11%, P = 0.03). At post-HTx year 10, the overall survival probability was 84% among patients treated with MCS and 90% among those medically managed (P = 0.32). At post-HTx year 1, freedom from treated rejections (≥ISHLT 2R) was 69% in the MCS group and 70% in the control group (P = 0.94); and freedom from any rejection was 8% and 5%, respectively (P = 0.98). There were no differences in renal function or cardiac allograft vasculopathy (grade ≥ 1) between groups at 1, 3, and 5 years post-HTx. CONCLUSIONS: Although patients treated with MCS had a higher frequency of pre-HTx allosensitization, there were no significant differences in post-HTx graft survival, biopsy-proven rejections, or renal function as compared with patients not bridged with MCS.
Assuntos
Insuficiência Cardíaca , Transplante de Coração , Coração Auxiliar , Adulto , Humanos , Masculino , Feminino , Insuficiência Cardíaca/cirurgia , Insuficiência Cardíaca/diagnóstico , Resultado do Tratamento , Coração Auxiliar/efeitos adversos , Estudos Retrospectivos , Fatores de Tempo , Transplante de Coração/efeitos adversosRESUMO
Background Cardiac involvement can be an initial manifestation in sarcoidosis. However, little is known about the association between various clinical phenotypes of cardiac sarcoidosis (CS) and outcomes. We aimed to analyze the relation of different clinical manifestations with outcomes of CS and to investigate the relative importance of clinical features influencing overall survival. Methods and Results A retrospective cohort of 141 patients with CS enrolled at 2 Swedish university hospitals was studied. Presentation, imaging studies, and outcomes of de novo CS and previously known extracardiac sarcoidosis were compared. Survival free of primary composite outcome (ventricular arrhythmias, heart transplantation, or death) was assessed. Machine learning algorithm was used to study the relative importance of clinical features in predicting outcome. Sixty-two patients with de novo CS and 79 with previously known extracardiac sarcoidosis were included. De novo CS showed more advanced New York Heart Association class (P=0.02), higher circulating levels of NT-proBNP (N-terminal pro-B-type natriuretic peptide) (P<0.001), and troponins (P<0.001), as well as a higher prevalence of right ventricular dysfunction (P<0.001). During a median (interquartile range) follow-up of 61 (44-77) months, event-free survival was shorter in patients with de novo CS (P<0.001). The top 5 features predicting worse event-free survival in order of importance were as follows: impaired tricuspid annular plane systolic excursion, de novo CS, reduced right ventricular ejection fraction, absence of ß-blockers, and lower left ventricular ejection fraction. Conclusions Patients with de novo CS displayed more severe disease and worse outcomes compared with patients with previously known extracardiac sarcoidosis. Using machine learning, right ventricular dysfunction and de novo CS stand out as strong overall predictors of impaired survival.
Assuntos
Cardiomiopatias , Sarcoidose , Disfunção Ventricular Direita , Humanos , Volume Sistólico , Função Ventricular Esquerda , Estudos Retrospectivos , Suécia/epidemiologia , Função Ventricular Direita , Sarcoidose/epidemiologiaRESUMO
The adult heart develops hypertrophy to reduce ventricular wall stress and maintain cardiac function in response to an increased workload. Although pathological hypertrophy generally progresses to heart failure, physiological hypertrophy may be cardioprotective. Cardiac-specific overexpression of the lipid-droplet protein perilipin 5 (Plin5) promotes cardiac hypertrophy, but it is unclear whether this response is beneficial. We analyzed RNA-sequencing data from human left ventricle and showed that cardiac PLIN5 expression correlates with up-regulation of cardiac contraction-related processes. To investigate how elevated cardiac Plin5 levels affect cardiac contractility, we generated mice with cardiac-specific overexpression of Plin5 (MHC-Plin5 mice). These mice displayed increased left ventricular mass and cardiomyocyte size but preserved heart function. Quantitative proteomics identified sarcoplasmic/endoplasmic reticulum Ca2+ ATPase 2 (SERCA2) as a Plin5-interacting protein. In situ proximity ligation assay further confirmed the Plin5/SERCA2 interaction. Live imaging showed increases in intracellular Ca2+ release during contraction, Ca2+ removal during relaxation, and SERCA2 function in MHC-Plin5 versus WT cardiomyocytes. These results identify a role of Plin5 in improving cardiac contractility through enhanced Ca2+ signaling.