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1.
BMJ Case Rep ; 12(8)2019 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-31387863

RESUMO

The pathophysiology of narrow complex dilated cardiomyopathy is not defined, so therapeutic options are limited. By utilising the velocity equation, the pathophysiology of narrow complex cardiomyopathy allows above normal conduction propagation velocities. There are two pathophysiological theories that allow above normal conduction velocities and failure to capture the myocardium: (1)insulating fibres of the conduction system extending beyond the apex and (2) reduction of axon branching. A patient with narrow complex cardiomyopathy was subjected to graded increase in amplitude and pulse width pacing to overcome the failure of native conduction to capture the myocardium. Peak systolic strain maps demonstrated a progressive increase in apical contractility with increasing pulse width and amplitude. Ejection fraction improved from 17% to 31%. Understanding the pathophysiology of narrow complex cardiomyopathy leads to proposed therapies. One potential pacing therapy is multi-lead pacing at high amplitude and pulse width to capture myocardial cells not captured by native conduction.


Assuntos
Cardiomiopatia Dilatada/fisiopatologia , Sistema de Condução Cardíaco/fisiopatologia , Idoso , Estimulação Cardíaca Artificial/métodos , Cardiomiopatia Dilatada/terapia , Desfibriladores Implantáveis , Feminino , Insuficiência Cardíaca/etiologia , Frequência Cardíaca , Humanos
3.
Curr Med Sci ; 39(4): 513-522, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31346984

RESUMO

Necroptosis is a non-apoptotic programmed cell death pathway, which causes necrosis-like morphologic changes and triggers inflammation in the surrounding tissues. Accumulating evidence has demonstrated that necroptosis is involved in a number of pathological processes that lead to cardiovascular diseases. However, the exact molecular pathways linking them remain unknown. Herein, this review summarizes the necroptosis-related pathways involved in the development of various cardiovascular diseases, including atherosclerosis, cardiac ischemia-reperfusion injury, cardiac hypertrophy, dilated cardiomyopathy and myocardial infarction, and may shed light on the diagnosis and treatment of these diseases.


Assuntos
Apoptose/genética , Doenças Cardiovasculares/genética , Morte Celular/genética , /genética , Aterosclerose/genética , Aterosclerose/fisiopatologia , Cardiomegalia/genética , Cardiomegalia/fisiopatologia , Cardiomiopatia Dilatada/genética , Cardiomiopatia Dilatada/fisiopatologia , Doenças Cardiovasculares/fisiopatologia , Humanos , Infarto do Miocárdio/genética , Infarto do Miocárdio/fisiopatologia , Traumatismo por Reperfusão/genética , Traumatismo por Reperfusão/fisiopatologia , Transdução de Sinais/genética
4.
Eur J Radiol ; 117: 178-183, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31307645

RESUMO

PURPOSE: Dilated cardiomyopathy (DCM) is a common form of cardiomyopathy and it is associated with poor outcomes. A poor prognosis of DCM patients with low ejection fraction has been noted in the short-term follow-up. Machine learning (ML) could aid clinicians in risk stratification and patient management after considering the correlation between numerous features and the outcomes. The present study aimed to predict the 1-year cardiovascular events in patients with severe DCM using ML, and aid clinicians in risk stratification and patient management. MATERIALS AND METHODS: The dataset used to establish the ML model was obtained from 98 patients with severe DCM (LVEF < 35%) from two centres. Totally 32 features from clinical data were input to the ML algorithm, and the significant features highly relevant to the cardiovascular events were selected by Information gain (IG). A naive Bayes classifier was built, and its predictive performance was evaluated using the area under the curve (AUC) of the receiver operating characteristics by 10-fold cross-validation. RESULTS: During the 1-year follow-up, a total of 22 patients met the criterion of the study end-point. The top features with IG > 0.01 were selected for ML model, including left atrial size (IG = 0.240), QRS duration (IG = 0.200), and systolic blood pressure (IG = 0.151). ML performed well in predicting cardiovascular events in patients with severe DCM (AUC, 0.887 [95% confidence interval, 0.813-0.961]). CONCLUSIONS: ML effectively predicted risk in patients with severe DCM in 1-year follow-up, and this may direct risk stratification and patient management in the future.


Assuntos
Cardiomiopatia Dilatada/fisiopatologia , Aprendizado de Máquina , Adulto , Idoso , Algoritmos , Teorema de Bayes , Cardiomiopatia Dilatada/mortalidade , Feminino , Humanos , Aprendizado de Máquina/tendências , Masculino , Pessoa de Meia-Idade , Prognóstico , Curva ROC
5.
J Stroke Cerebrovasc Dis ; 28(9): 2453-2458, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31311695

RESUMO

BACKGROUND: Although the incidence of cerebral infarction is higher in Duchenne muscular dystrophy (.75 per 100) than in the general population (7.5-11.4 per 100 000), only 18 cases have been reported, and prevention and management guidelines for infarction in this disorder remain lacking. PATIENTS AND METHODS: We encountered 2 cases of Duchenne muscular dystrophy with cerebral infarction. To clarify risk factors for such infarction in Duchenne muscular dystrophy, we reviewed 20 cases, including our 2 patients. RESULTS: Age at onset of infarction ranged from 4 to 31 years (n = 19). Most patients were 16-21 years old (14 of 19; 73.7%). Eighteen patients (90%) had dilated cardiomyopathy (DCM), showing a higher frequency than in the age-matched general Duchenne muscular dystrophy population. Left ventricular ejection fraction (LVEF) ranged from 10.2% to 42% (median, 20%; n = 9). Detectable cardiac thrombus and atrial fibrillation were rare (2 of 17; 11.8%, and 1 of 17; 5.9%, respectively). CONCLUSIONS: Presence of DCM with low LVEF seems to be the strongest risk factor for cerebral infarction in Duchenne muscular dystrophy.


Assuntos
Infarto Cerebral/etiologia , Distrofia Muscular de Duchenne/complicações , Adolescente , Adulto , Fatores Etários , Cardiomiopatia Dilatada/etiologia , Cardiomiopatia Dilatada/fisiopatologia , Infarto Cerebral/diagnóstico por imagem , Infarto Cerebral/fisiopatologia , Infarto Cerebral/terapia , Criança , Pré-Escolar , Imagem de Difusão por Ressonância Magnética , Nível de Saúde , Humanos , Masculino , Limitação da Mobilidade , Distrofia Muscular de Duchenne/diagnóstico , Distrofia Muscular de Duchenne/fisiopatologia , Distrofia Muscular de Duchenne/terapia , Prognóstico , Medição de Risco , Fatores de Risco , Volume Sistólico , Função Ventricular Esquerda , Adulto Jovem
6.
G Ital Cardiol (Rome) ; 20(6): 392-395, 2019 Jun.
Artigo em Italiano | MEDLINE | ID: mdl-31184326

RESUMO

The diagnostic approach to patients with cardiac sarcoidosis is challenging, as the disease may occur as a subclinical entity or have heterogeneous clinical manifestations ranging from ventricular arrhythmias to advanced cardiac failure. Therefore, while clinical suspicion remains key, imaging techniques such as nuclear magnetic resonance imaging and myocardial scintigraphy play an important confirmatory role. Final diagnosis requires histological proof on cardiac or extracardiac biopsy. A multidisciplinary context is essential for appropriate diagnosis, staging and management. We present the case of a young man with dilated cardiomyopathy in whom, following the onset of malignant and recurrent ventricular arrhythmias, a final diagnosis of cardiac sarcoidosis was reached based on a host of invasive and non-invasive diagnostic techniques, allowing tailored treatment.


Assuntos
Arritmias Cardíacas/etiologia , Cardiomiopatia Dilatada/complicações , Sarcoidose/complicações , Adulto , Cardiomiopatia Dilatada/fisiopatologia , Cardiopatias/complicações , Humanos , Masculino
7.
Nat Rev Dis Primers ; 5(1): 32, 2019 05 09.
Artigo em Inglês | MEDLINE | ID: mdl-31073128

RESUMO

Dilated cardiomyopathy (DCM) is a clinical diagnosis characterized by left ventricular or biventricular dilation and impaired contraction that is not explained by abnormal loading conditions (for example, hypertension and valvular heart disease) or coronary artery disease. Mutations in several genes can cause DCM, including genes encoding structural components of the sarcomere and desmosome. Nongenetic forms of DCM can result from different aetiologies, including inflammation of the myocardium due to an infection (mostly viral); exposure to drugs, toxins or allergens; and systemic endocrine or autoimmune diseases. The heterogeneous aetiology and clinical presentation of DCM make a correct and timely diagnosis challenging. Echocardiography and other imaging techniques are required to assess ventricular dysfunction and adverse myocardial remodelling, and immunological and histological analyses of an endomyocardial biopsy sample are indicated when inflammation or infection is suspected. As DCM eventually leads to impaired contractility, standard approaches to prevent or treat heart failure are the first-line treatment for patients with DCM. Cardiac resynchronization therapy and implantable cardioverter-defibrillators may be required to prevent life-threatening arrhythmias. In addition, identifying the probable cause of DCM helps tailor specific therapies to improve prognosis. An improved aetiology-driven personalized approach to clinical care will benefit patients with DCM, as will new diagnostic tools, such as serum biomarkers, that enable early diagnosis and treatment.


Assuntos
Cardiomiopatia Dilatada/diagnóstico , Cardiomiopatia Dilatada/terapia , Autoimunidade/genética , Autoimunidade/fisiologia , Terapia de Ressincronização Cardíaca/métodos , Cardiomiopatia Dilatada/fisiopatologia , Ecocardiografia/métodos , Eletrocardiografia/métodos , Insuficiência Cardíaca/etiologia , Humanos , Inflamação/complicações , Inflamação/fisiopatologia , Imagem por Ressonância Magnética/métodos , Prognóstico , Qualidade de Vida/psicologia , Fatores Sexuais
9.
Intern Med ; 58(17): 2535-2538, 2019 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-31118397

RESUMO

A 79-year-old man with dilated cardiomyopathy and severe functional mitral regurgitation presented with general fatigue and dyspnea. Auscultation revealed a systolic regurgitant murmur with a minimized second heart sound due to a low output. On the other hand, the third heart sound was ultimately enhanced, being visible and palpable as a pulsatile knock of the precordium. Phonocardiography and echocardiography successfully confirmed early-diastolic rapid distension of the left ventricle along with rapid ventricular filling and abrupt deceleration of the atrioventricular blood flow to be the precise etiology of the ultimate third heart sound, indicating critically deteriorated hemodynamics due to massive mitral regurgitation combined with a low output.


Assuntos
Cardiomiopatia Dilatada/fisiopatologia , Ruídos Cardíacos/fisiologia , Insuficiência da Valva Mitral/fisiopatologia , Idoso , Baixo Débito Cardíaco/fisiopatologia , Dispneia/etiologia , Ecocardiografia , Fadiga/etiologia , Auscultação Cardíaca , Hemodinâmica/fisiologia , Humanos , Masculino , Fonocardiografia , Disfunção Ventricular Esquerda/fisiopatologia
10.
Pan Afr Med J ; 32: 34, 2019.
Artigo em Francês | MEDLINE | ID: mdl-31143339

RESUMO

We here report the case of a 38-year old woman with dilated cardiomyopathy induced by hypocalcaemia secondary to hypoparathyroidism. The patient had low calcium level (30 mg/L) and echocardiography showed dilated-hypokinetic cardiomyopathy with reduced left ventricular ejection fraction (31.4%). She received calcitherapy associated with vitamin D3 and her evolution was marked by the normalization of the size of the cardiac cavities and of the left ventricular ejection fraction after normocalcemia.


Assuntos
Cardiomiopatia Dilatada/etiologia , Hipocalcemia/complicações , Hipoparatireoidismo/complicações , Tireoidectomia/métodos , Adulto , Cálcio/administração & dosagem , Cálcio/sangue , Cardiomiopatia Dilatada/diagnóstico , Cardiomiopatia Dilatada/fisiopatologia , Colecalciferol/administração & dosagem , Feminino , Humanos , Hipocalcemia/etiologia , Hipoparatireoidismo/etiologia , Volume Sistólico , Resultado do Tratamento
11.
Hypertension ; 74(1): 47-55, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31132949

RESUMO

Emerging preclinical data suggest that splanchnic sympathetic nerve activation may play an important role in the pathophysiology of hypertension. We sought to determine the potential therapeutic application of catheter-based splanchnic denervation in a clinically relevant large animal model of hypertensive cardiomyopathy (hCMP). Sustained elevated blood pressure was induced in adult pigs using a combination of intravenous infusion of Ang II (angiotensin II) and subcutaneous implantation of deoxycorticosterone acetate pellets to establish a large animal model of hCMP. Serial changes in cardiac echocardiographic and invasive hemodynamic parameters and neurohumoral biomarkers were investigated in animals with hypertension alone (n=9) and hypertension with catheter-based splanchnic denervation (n=6). Another 6 pigs without hypertension induction served as controls. At 10 weeks, hypertensive animals developed sustained elevated blood pressure and phenotype of hCMP with significant systolic and diastolic dysfunction, and left ventricular remodeling and hypertrophy as determined by invasive hemodynamic and echocardiogram assessments, respectively, and increased venoarterial norepinephrine gradient over the myocardium, kidneys, and splanchnic organs compared with baseline. Catheter-based splanchnic denervation decreased the venoarterial norepinephrine gradient over the splanchnic organs associated with the reduced splenic sympathetic nerve innervation; attenuated the elevated blood pressure, left ventricular remodeling, and hypertrophy; and preserved left ventricular systolic and diastolic function at 20 weeks in pigs with hCMP. Our results provide novel mechanistic insight into the role of splenic sympathetic nerve innervation in hypertension and important proof-of-principle data for the therapeutic application of catheter-based splanchnic denervation in a large animal model of hCMP.


Assuntos
Cateterismo Cardíaco/métodos , Cardiomiopatia Dilatada/cirurgia , Hipertensão/cirurgia , Nervos Esplâncnicos/cirurgia , Simpatectomia/métodos , Remodelação Ventricular/fisiologia , Análise de Variância , Animais , Determinação da Pressão Arterial , Cardiomiopatia Dilatada/fisiopatologia , Modelos Animais de Doenças , Ecocardiografia/métodos , Feminino , Hemodinâmica , Hipertensão/fisiopatologia , Distribuição Aleatória , Valores de Referência , Medição de Risco , Sus scrofa , Resultado do Tratamento
12.
Minerva Cardioangiol ; 67(4): 261-271, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31115242

RESUMO

BACKGROUND: Since left ventricular reverse remodeling (LVRR) and sphericity index (SI) are correlated with DCM patients' survival, we attempted to establish the relationship between LVRR, SI and left ventricle (LV) dimensions. METHODS: In 70 DCM patients, we measured EF, LV transverse (sLVd) and longitudinal (lLVd) diameters at hospital admission, then after 3 and 12 months. SI was assessed thus: SI=sLVd/lLVd. RESULTS: LVRR was present in 32 patients (52%). SI measurements were similar in LVRR-present and -absent groups at baseline (0.71 vs. 0.70) and differed after 3 and 12 months (0.61 vs. 0.72, P<0.005; 0.59 vs. 0.73, P<0.001; respectively). During 12 months, SI and sLVd decreased in the LVRR-present (0.71 vs. 0.61 vs. 0.59, P<0.05; 5.75 vs. 5.00 vs. 4.82 cm, P<0.001; respectively) and increased in the LVRR-absent cohort (0.70 vs. 0.72 vs. 0.73, P<0.001; 6.01 vs. 6.15 vs. 6.67, P<0.001; respectively). lLVd remained stable (8.23 vs. 8.16 vs. 8.38cm; 8.66 vs. 8.85 vs. 9.13 cm; respectively). SI was significantly correlated with sLVd but not with lLVd. At 3-month follow-up, SI (P<0.005, OR=14000 [95% CI: 5 - 3.9*107]) was found to be a significant LVRR predictor via univariate logistic regression. CONCLUSIONS: To summarize, changes in sLVd are crucial for changes in LV geometry, whereas lLVd has a negligible effect on this process. The presence of LVRR was not always associated with an improvement in SI and its absence with increase in SI. Since the assessment of SI is less complex than LVRR, SI as a significant LVRR predictor can be useful part of a regular echocardiography examination.


Assuntos
Cardiomiopatia Dilatada/fisiopatologia , Disfunção Ventricular Esquerda/fisiopatologia , Função Ventricular Esquerda/fisiologia , Remodelação Ventricular/fisiologia , Adulto , Cardiomiopatia Dilatada/diagnóstico por imagem , Ecocardiografia , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Disfunção Ventricular Esquerda/diagnóstico por imagem
13.
J Cardiovasc Med (Hagerstown) ; 20(7): 450-458, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30985353

RESUMO

OBJECTIVE: The objective was to provide an exhaustive characterization of ECG features in a large cohort of dilated cardiomyopathies (DCMs) and then investigate their possible prognostic role in the long term. BACKGROUND: ECG is an accessible, reproducible, low-cost diagnostic and prognostic tool. However, an extensive description of ECG features and their long-term prognostic role in a large cohort of DCM is lacking. METHODS: All available baseline ECGs of DCM patients enrolled from 1992 to 2013 were systematically analysed. Patients underwent to a complete clinical-laboratory evaluation. The study outcome measures were death or heart transplant (D/HT) and sudden death or malignant ventricular arrhythmias (SD/MVA). RESULTS: Four hundred and fourteen DCM patients were enrolled. During a median follow-up of 125 months, 55 and 57 patients experienced D/HT and SD/MVA, respectively. At multivariate analysis, left ventricular hypertrophy (P = 0.017), heart rate (HR, P = 0.005) and anterolateral T-wave inversion (P = 0.041) predicted D/HT. Regarding SD/MVA, S wave amplitude in V2 (P = 0.008), R wave amplitude in DIII (P = 0.007), anterolateral T-wave inversion (P = 0.017) emerged as predictors. At receiver-operating curve analyses, the addition of ECG models to the clinical-laboratory evaluation significantly increased the area under the curve both for D/HT (from 0.68 to 0.74, P = 0.042) and SD/MVA (from 0.70 to 0.77, P = 0.048). CONCLUSION: The exhaustive systematic evaluation of ECG has an incremental impact in the prognostication of a large cohort of DCM patients, also regarding the arrhythmic stratification.


Assuntos
Cardiomiopatia Dilatada/diagnóstico , Eletrocardiografia , Frequência Cardíaca , Adulto , Arritmias Cardíacas/diagnóstico por imagem , Arritmias Cardíacas/mortalidade , Arritmias Cardíacas/fisiopatologia , Cardiomiopatia Dilatada/mortalidade , Cardiomiopatia Dilatada/fisiopatologia , Cardiomiopatia Dilatada/cirurgia , Morte Súbita Cardíaca/epidemiologia , Feminino , Transplante de Coração , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Prognóstico , Estudos Retrospectivos , Fatores de Risco , Fatores de Tempo
14.
PLoS One ; 14(4): e0215818, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31009519

RESUMO

This study aimed to analyze changes in the expression of autophagy- and phagocytosis-related genes in patients with dilated cardiomyopathy (DCM), especially in relation to left ventricular (LV) dysfunction. Furthermore, transmission electron microscopy of the diseased tissue was carried out to investigate if the gene expression changes are translated into ultrastructural alterations. LV tissue samples from patients with DCM (n = 13) and from controls (CNT; n = 10) were analyzed by RNA-sequencing, whereupon the altered expression (P < 0.05) of 13 autophagy- and 3 phagocytosis-related genes was observed. The expression changes of the autophagy-related genes NRBP2 and CALCOCO2 were associated with cardiac dysfunction and remodeling (P < 0.05). The affected patients had a higher activity of these degradation processes, as evidenced by the greater number of autophagic structures in the DCM tissue (P < 0.001). Differences in the ultrastructural distribution were also found between the DCM and CNT tissues. These results show that in patients with DCM, the altered expression of NRBP2 and CALCOCO2 is related to LV dysfunction and remodeling. Clarification of the molecular mechanisms of cardiac autophagy would help in the future development of therapies to improve LV performance.


Assuntos
Cardiomiopatia Dilatada/genética , Proteínas Nucleares/genética , RNA Mensageiro/genética , Receptores Citoplasmáticos e Nucleares/genética , Disfunção Ventricular Esquerda/genética , Antagonistas Adrenérgicos beta/uso terapêutico , Adulto , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Autofagia/genética , Cardiomiopatia Dilatada/tratamento farmacológico , Cardiomiopatia Dilatada/metabolismo , Cardiomiopatia Dilatada/fisiopatologia , Estudos de Casos e Controles , Diuréticos/uso terapêutico , Feminino , Perfilação da Expressão Gênica , Regulação da Expressão Gênica , Ventrículos do Coração/metabolismo , Ventrículos do Coração/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Antagonistas de Receptores de Mineralocorticoides/uso terapêutico , Miocárdio/metabolismo , Miocárdio/patologia , Proteínas Nucleares/metabolismo , RNA Mensageiro/metabolismo , Receptores Citoplasmáticos e Nucleares/metabolismo , Análise de Sequência de RNA , Disfunção Ventricular Esquerda/tratamento farmacológico , Disfunção Ventricular Esquerda/metabolismo , Disfunção Ventricular Esquerda/fisiopatologia
15.
Turk Kardiyol Dern Ars ; 47(3): 207-215, 2019 Apr.
Artigo em Turco | MEDLINE | ID: mdl-30982820

RESUMO

OBJECTIVE: Dilated cardiomyopathy (DCM) is a disorder featuring left ventricular dysfunction, heart failure, and a poor prognosis. The etiology is still unclear, despite diagnostic and therapeutic developments. This study was an evaluation of factors affecting the life span of a group of idiopathic DCM patients. METHODS: A total of 79 patients from between October 2005 and October 2017 with a diagnosis of idiopathic DCM were evaluated retrospectively. Demographic characteristics, clinical information, left ventricular function, treatment, and follow-up of the patients were reviewed based on hospital records. Age, gender, parental consanguinity, cardiomegaly on telecardiography, reduced ejection fraction (EF) and shortening fraction (SF), degree of mitral regurgitation, and intracardiac thrombosis were determined to affect prognosis. RESULTS: The patients were aged 20+-60 months, and the male/female ratio was 1.02/1. The patients most frequently presented with heart failure signs and symptoms (n=59, 74.7%). The most common physical examination findings were a murmur (n=53, 67.1%) and tachycardia (n=48, 60.8%). Cardiomegaly was observed on telecardiography in 73.4% of the patients. The EF and SF values were 35.7+-12.6% and 17.3+-6.5%, respectively. In all, 42 (53.2%) patients had mitral regurgitation of grade 2 or higher. The duration of follow-up was between 1 and 156 months (20+-34.9 months). Intracardiac thrombosis was detected in 4 (5.1%) patients. The mortality rate was 36.7%. When the prognostic factors were compared according to survival time, it was determined that survival was reduced in cases of parental consanguinity, low EF, and cardiomegaly. CONCLUSION: The most important negative markers affecting the length of survival of DCM patients were parental consanguinity, cardiomegaly detected on telecardiography, and a reduced EF level.


Assuntos
Cardiomiopatia Dilatada/epidemiologia , Disfunção Ventricular Esquerda/fisiopatologia , Adolescente , Cardiomegalia/diagnóstico por imagem , Cardiomiopatia Dilatada/mortalidade , Cardiomiopatia Dilatada/fisiopatologia , Criança , Serviços de Saúde da Criança , Pré-Escolar , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Prognóstico , Estudos Retrospectivos , Análise de Sobrevida , Turquia/epidemiologia
16.
Gen Thorac Cardiovasc Surg ; 67(11): 925-933, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30972531

RESUMO

OBJECTIVES: To analyze our surgical experiences with surgical ventricular restoration (SVR) for dilated ischemic cardiomyopathy (ICM) and to determine the significance of preoperative right ventricular (RV) function on outcomes. METHODS AND RESULTS: This study retrospectively analyzed 19 patients who underwent SVR between April 2010 and May 2016. Their mean age and New York Heart Association functional class were 62 ± 11 years and 2.9 ± 0.8, respectively. The preoperative mean left ventricular (LV) end-systolic volume index and LV ejection fraction (LVEF) were 134 ± 56 mL/m2 and 24 ± 7%, respectively. The preoperative mean RV fractional area change (RVFAC) to quantify RV systolic function was 33 ± 13%, as assessed by transthoracic echocardiography. The mean follow-up period was 47 ± 20 months. Three patients died of cardiac causes during the follow-up, with the 3-year and 5-year freedoms from cardiac-related death of 89% and 79%, respectively. Major adverse cardiac events (MACEs) occurred in ten patients, with the 3-year and 5-year MACE-free survival rates of 58% and 41%, respectively. RVFAC (risk ratio [RR] = 0.92, 95% confidence interval [CI] 0.86-0.98, p = 0.01) and LVEF (RR = 0.83, 95% CI 0.68-0.97, p = 0.02) were significant predictors of MACEs in the multivariate analysis. Patients with RVFAC of < 35% had significantly poorer MACE-free survival rates (33% at 3 years) than those with RVFAC of ≥ 35% (80% at 3 years). CONCLUSION: SVR for ICM provided acceptable freedom from cardiac-related death; however, MACEs commonly occurred and was associated with RV dysfunction.


Assuntos
Cardiomiopatia Dilatada/fisiopatologia , Cardiomiopatia Dilatada/cirurgia , Disfunção Ventricular Direita/fisiopatologia , Função Ventricular Direita , Adulto , Idoso , Ecocardiografia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Isquemia Miocárdica/cirurgia , Estudos Retrospectivos , Volume Sistólico , Taxa de Sobrevida , Sístole , Resultado do Tratamento , Disfunção Ventricular Direita/diagnóstico por imagem , Função Ventricular Esquerda
17.
Nat Biomed Eng ; 3(2): 147-157, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30923642

RESUMO

Dilated cardiomyopathy (DCM) is a leading cause of morbidity and mortality worldwide; yet how genetic variation and environmental factors impact DCM heritability remains unclear. Here, we report that compound genetic interactions between DNA sequence variants contribute to the complex heritability of DCM. By using genetic data from a large family with a history of DCM, we discovered that heterozygous sequence variants in the TROPOMYOSIN 1 (TPM1) and VINCULIN (VCL) genes cose-gregate in individuals affected by DCM. In vitro studies of patient-derived and isogenic human-pluripotent-stem-cell-derived cardio-myocytes that were genome-edited via CRISPR to create an allelic series of TPM1 and VCL variants revealed that cardiomyocytes with both TPM1 and VCL variants display reduced contractility and sarcomeres that are less organized. Analyses of mice genetically engineered to harbour these human TPM1 and VCL variants show that stress on the heart may also influence the variable penetrance and expressivity of DCM-associated genetic variants in vivo. We conclude that compound genetic variants can interact combinatorially to induce DCM, particularly when influenced by other disease-provoking stressors.


Assuntos
Cardiomiopatia Dilatada/genética , Predisposição Genética para Doença , Variação Genética , Animais , Cardiomiopatia Dilatada/fisiopatologia , Matriz Extracelular/metabolismo , Feminino , Regulação da Expressão Gênica , Humanos , Padrões de Herança/genética , Masculino , Camundongos , Modelos Biológicos , Contração Muscular/genética , Miócitos Cardíacos/metabolismo , Miócitos Cardíacos/patologia , Linhagem , Células-Tronco Pluripotentes/metabolismo , Regulação para Cima/genética
18.
Echocardiography ; 36(4): 702-706, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30868655

RESUMO

BACKGROUND: The differentiation between dilated cardiomyopathy (DCM) and systolic dysfunction caused by coronary artery disease (CAD) based on clinical and echocardiographic presentation can be difficult in some cases. AIM: Our study aimed to define differences in myocardial function between patients with ischemic and nonischemic etiology of reduced left ventricular ejection fraction using 2D speckle tracking echocardiography (STE). MATERIAL AND METHODS: We retrospectively analyzed 90 patients (mean age 65 ± 11 years, 70% male) with de novo diagnosed reduced left ventricular ejection fraction (≤45% as determined by the transthoracic echocardiography), who were referred for coronary angiography to determine the presence of significant CAD. On the basis of coronary angiography results, patients were divided into two subgroups as follows: 45 subjects with significant CAD (group A) and 45 subjects without CAD (group B). Acquired transthoracic echocardiographic images were assessed off-line using 2DSTE. In each patient, we calculated arithmetic mean, median value, and standard deviation of regional longitudinal strain and strain rate of 18 left ventricular segments. RESULTS: Standard deviation of the regional peak early diastolic strain rate was significantly higher in group A than in group B (P = 0.01). The cutoff value with the highest diagnostic value was >0.37/s-its sensitivity and specificity for the diagnosis of CAD were 73% and 53%, respectively. The remaining parameters did not differ significantly between the study groups. CONCLUSIONS: Patients with systolic dysfunction resulting from CAD have significantly more heterogeneous regional longitudinal early diastolic strain rate assessed by 2DSTE than patients with DCM.


Assuntos
Cardiomiopatia Dilatada/diagnóstico por imagem , Doença da Artéria Coronariana/diagnóstico por imagem , Ecocardiografia/métodos , Disfunção Ventricular Esquerda/diagnóstico por imagem , Idoso , Cardiomiopatia Dilatada/complicações , Cardiomiopatia Dilatada/fisiopatologia , Doença da Artéria Coronariana/complicações , Doença da Artéria Coronariana/fisiopatologia , Diagnóstico Diferencial , Feminino , Ventrículos do Coração/diagnóstico por imagem , Ventrículos do Coração/fisiopatologia , Humanos , Interpretação de Imagem Assistida por Computador/métodos , Masculino , Pessoa de Meia-Idade , Reprodutibilidade dos Testes , Estudos Retrospectivos , Sensibilidade e Especificidade , Disfunção Ventricular Esquerda/etiologia , Disfunção Ventricular Esquerda/fisiopatologia
19.
Cell Physiol Biochem ; 52(3): 435-438, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30873819

RESUMO

BACKGROUND/AIMS: Tachycardiomyopathy (TCM) is a largely reversible form of non-ischemic heart failure. The underlying mechanism are, however, still today poorly understood. Recent data indicate distinct changes in mitochondrial distribution in these patients, compared to other non-ischemic cardiomyopathies.This study investigated underlying mechanisms in mitochondrial dynamics in endomyocardial biopsy samples (EMB) from patients with TCM and compared them to patients with dilated cardiomyopathy (DCM), which show similar clinical features. METHODS: Focused mRNA analyses were performed on routinely obtained paraffinfixed EMB specimen from patients fulfilling TCM diagnosis criteria, as well as patients with DCM to elucidate regulatory changes in mitochondrial fusion, fission and mitophagy. RESULTS: In patients with TCM we were able to identify mRNA of Mitofusin 1 and 2, two effector proteins regulating mitochondrial fusion, to be strongly upregulated compared to patients with DCM. Conclusively, we did not find differences in the mRNA expression of mitochondrial fission regulators including DRP1, Fis1, MFF, MiD49, and MiD51. Furthermore, we did not find significant changes in PINK1 expression, an important mediator for mitochondrial autophagy. CONCLUSION: The mRNA upregulation of Mitofusin 1 and 2 provides first insight into the complex changes of mitochondrial dynamics in cardiomyocytes of patients with reversible heart failure due to TCM.


Assuntos
Cardiomiopatia Dilatada/genética , GTP Fosfo-Hidrolases/genética , Mitocôndrias/genética , Dinâmica Mitocondrial/genética , Proteínas de Transporte da Membrana Mitocondrial/genética , Proteínas Mitocondriais/genética , RNA Mensageiro/genética , Biópsia , Cardiomiopatia Dilatada/classificação , Cardiomiopatia Dilatada/diagnóstico , Cardiomiopatia Dilatada/fisiopatologia , GTP Fosfo-Hidrolases/metabolismo , Regulação da Expressão Gênica , Frequência Cardíaca/fisiologia , Humanos , Proteínas de Membrana/genética , Proteínas de Membrana/metabolismo , Proteínas Associadas aos Microtúbulos/genética , Proteínas Associadas aos Microtúbulos/metabolismo , Mitocôndrias/metabolismo , Mitocôndrias/patologia , Proteínas de Transporte da Membrana Mitocondrial/metabolismo , Proteínas Mitocondriais/metabolismo , Miócitos Cardíacos/metabolismo , Miócitos Cardíacos/patologia , Fatores de Alongamento de Peptídeos/genética , Fatores de Alongamento de Peptídeos/metabolismo , Proteínas Quinases/genética , Proteínas Quinases/metabolismo , RNA Mensageiro/metabolismo
20.
Transplant Proc ; 51(2): 369-371, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30879543

RESUMO

OBJECTIVES: To evaluate whether the levels of some molecules implicated in nucleocytoplasmic transport in human cardiomyocytes are related to the severity of heart failure (HF) in patients on the heart transplantation (HT) waiting list, and to determine whether there is a differential pattern of molecular alteration between ischemic cardiomyopathy (ICM) and non-ischemic dilated cardiomyopathy (DCM). METHODS: Sixty-three blood samples collected before HT were analyzed to identify the levels of IMPORTIN5 (IMP5); IMPORTINalpha2; ATPaseCaTransp (ATPCa); NUCLEOPORIN153kDa (Nup153); NUCLEOPORIN160kDa (Nup160); RANGTPaseAP1 (RanGAP1) and EXPORTIN4 (EXP4). These data were then compared between patients with advanced HF with or without the need for ventricular support with extracorporeal membrane oxygenation (ECMO) as a bridge for HT, as well as between patients with non-ischemic DCM and patients with ICM. RESULTS: Thirty-three patients had ICM, 26 had non-ischemic DCM, and 4 had heart disease. Seventeen patients required ventricular assistance as a bridge to HT. The levels of ATPCa, RanGAP1, and IMP5 were significantly higher in patients with ECMO, while EXP4 was significantly higher in patients without ECMO. Patients with DCM showed higher levels of IMP5, RanGAP1, and Nup153 than those with ICM. CONCLUSION: Patients with advanced HF in critical condition (with ECMO as a bridge for HT) presented with significantly higher levels of ATPCa, RanGAP1, and IMP5, while patients with DCM had significantly higher levels of RanGAP1, IMP5, and Nup153. It remains to be clarified whether the determination of these molecules would facilitate the early identification of this group or if their alteration occurs as consequence of circulatory support with ECMO.


Assuntos
Transporte Ativo do Núcleo Celular/fisiologia , Insuficiência Cardíaca/metabolismo , Miócitos Cardíacos/metabolismo , Adulto , Cardiomiopatia Dilatada/complicações , Cardiomiopatia Dilatada/metabolismo , Cardiomiopatia Dilatada/fisiopatologia , Feminino , Insuficiência Cardíaca/etiologia , Insuficiência Cardíaca/fisiopatologia , Transplante de Coração , Humanos , Masculino , Pessoa de Meia-Idade , Isquemia Miocárdica/complicações , Isquemia Miocárdica/metabolismo , Isquemia Miocárdica/fisiopatologia , Medição de Risco , Listas de Espera
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