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1.
Int J Cardiovasc Imaging ; 36(11): 2229-2238, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32666169

RESUMO

Diffusion-weighted imaging (DWI) has been confirmed to be associated with late gadolinium enhancement (LGE) in hypertrophic cardiomyopathy (HCM). In this context, we aimed to study whether DWI could reflect the active tissue injury and edema information of HCM which were usually indicated by T2 weighted images. Forty HCM patients were examined using a 3.0 T magnetic resonance scanner. Cine, T2-weighted short tau inversion recovery (T2-STIR), DWI and LGE sequences were acquired. T1 mapping was also included to quantify the focal and diffuse fibrosis. Cardiac troponin I (cTnI) was tested to assess the recently myocardial injury. Student's t-test, Mann-Whitney U test, One-way analysis, Kruskal-Wallis analysis, the Spearman correlation analysis, and multivariable regression were used in this study. The apparent diffusion coefficient (ADC) was significantly elevated in the cTnI positive group (P = 0.01) and correlated with LGE (ρ = 0.312, P = 0.049) and HighT2 extent (ρ = 0.443, P = 0.004) in the global level. In the segmental analysis, the ADC significantly differentiated the segments with and without HighT2/LGE presence (P = 0.00). The average ADC values were higher in segments with HighT2 and LGE coexistence than in those with only LGE presence (P < 0.05). Multivariable regression indicated that segmental HighT2 and LGE were both contributing factors to the ADC values. In this study of HCM, we confirmed that ADC as a molecular diffusion parameter reflects the replacement fibrosis of myocardium. Moreover, it also reveals edema extent and its association with serum cTnI.


Assuntos
Cardiomiopatia Hipertrófica/diagnóstico por imagem , Meios de Contraste/administração & dosagem , Imagem de Difusão por Ressonância Magnética , Edema Cardíaco/diagnóstico por imagem , Gadolínio DTPA/administração & dosagem , Imagem Cinética por Ressonância Magnética , Miocárdio/patologia , Adulto , Idoso , Biomarcadores/sangue , Cardiomiopatia Hipertrófica/sangue , Cardiomiopatia Hipertrófica/patologia , Edema Cardíaco/sangue , Edema Cardíaco/patologia , Feminino , Fibrose , Humanos , Masculino , Pessoa de Meia-Idade , Miocárdio/metabolismo , Valor Preditivo dos Testes , Troponina I/sangue
2.
Open Heart ; 7(1): e001152, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32201584

RESUMO

Background: Hypertrophic cardiomyopathy (HCM) is associated with an increased risk of adverse cardiac events. Beyond classic risk factors, relative myocardial ischaemia and succeeding myocardial alterations, which can be detected using either contrast agents or parametric mapping in cardiovascular magnetic resonance (CMR) imaging, have shown an impact on outcome in HCM. CMR may help to risk stratify using parametric T2* mapping. Therefore, the aim of the present study was to evaluate the association of T2* values or fibrosis with cardiovascular events in HCM. Methods: The relationship between T2* with supraventricular, ventricular arrhythmia or heart failure was retrospectively assessed in 91 patients with HCM referred for CMR on a 1.5T MR imaging system. Fibrosis as a reference was added to the model. Patients were subdivided into groups according to T2* value quartiles. Results: 47 patients experienced an event of ventricular arrhythmia, 25 of atrial fibrillation/flutter and 17 of heart failure. T2*≤28.7 ms yielded no association with ventricular events in the whole HCM cohort. T2* of non-obstructive HCM showed a significant association with ventricular events in univariate analysis, but not in multivariate analysis. For the combined endpoint of arrhythmic events, there was already an association for the whole HCM cohort, but again only in univariate analyses. Fibrosis stayed the strongest predictor in all analyses. There was no association for T2* and fibrosis with heart failure. Conclusions: Decreased T2* values by CMR only provide a small association with arrhythmic events in HCM, especially in non-obstructive HCM. No information is added for heart failure.


Assuntos
Cardiomiopatia Hipertrófica/diagnóstico por imagem , Imagem Cinética por Ressonância Magnética , Miocárdio/patologia , Adulto , Idoso , Arritmias Cardíacas/etiologia , Biomarcadores/sangue , Cardiomiopatia Hipertrófica/sangue , Cardiomiopatia Hipertrófica/complicações , Cardiomiopatia Hipertrófica/patologia , Progressão da Doença , Feminino , Fibrose , Insuficiência Cardíaca/etiologia , Humanos , Masculino , Pessoa de Meia-Idade , Miocárdio/metabolismo , Valor Preditivo dos Testes , Prognóstico , Estudos Retrospectivos , Fatores de Risco , Troponina T/sangue
3.
Mol Cell Proteomics ; 19(1): 114-127, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31243064

RESUMO

Hypertrophic cardiomyopathy (HCM) is defined by pathological left ventricular hypertrophy (LVH). It is the commonest inherited cardiac condition and a significant number of high risk cases still go undetected until a sudden cardiac death (SCD) event. Plasma biomarkers do not currently feature in the assessment of HCM disease progression, which is tracked by serial imaging, or in SCD risk stratification, which is based on imaging parameters and patient/family history. There is a need for new HCM plasma biomarkers to refine disease monitoring and improve patient risk stratification. To identify new plasma biomarkers for patients with HCM, we performed exploratory myocardial and plasma proteomics screens and subsequently developed a multiplexed targeted liquid chromatography-tandem/mass spectrometry-based assay to validate the 26 peptide biomarkers that were identified. The association of discovered biomarkers with clinical phenotypes was prospectively tested in plasma from 110 HCM patients with LVH (LVH+ HCM), 97 controls, and 16 HCM sarcomere gene mutation carriers before the development of LVH (subclinical HCM). Six peptides (aldolase fructose-bisphosphate A, complement C3, glutathione S-transferase omega 1, Ras suppressor protein 1, talin 1, and thrombospondin 1) were increased significantly in the plasma of LVH+ HCM compared with controls and correlated with imaging markers of phenotype severity: LV wall thickness, mass, and percentage myocardial scar on cardiovascular magnetic resonance imaging. Using supervised machine learning (ML), this six-biomarker panel differentiated between LVH+ HCM and controls, with an area under the curve of ≥ 0.87. Five of these peptides were also significantly increased in subclinical HCM compared with controls. In LVH+ HCM, the six-marker panel correlated with the presence of nonsustained ventricular tachycardia and the estimated five-year risk of sudden cardiac death. Using quantitative proteomic approaches, we have discovered six potentially useful circulating plasma biomarkers related to myocardial substrate changes in HCM, which correlate with the estimated sudden cardiac death risk.


Assuntos
Cardiomiopatia Hipertrófica/sangue , Hipertrofia Ventricular Esquerda/sangue , Aprendizado de Máquina , Peptídeos/sangue , Proteômica/métodos , Adulto , Idoso , Biomarcadores/sangue , Cardiomiopatia Hipertrófica/diagnóstico , Estudos de Casos e Controles , Feminino , Humanos , Hipertrofia Ventricular Esquerda/diagnóstico , Masculino , Pessoa de Meia-Idade , Mutação , Fenótipo , Valor Preditivo dos Testes , Estudos Prospectivos , Sarcômeros/genética , Índice de Gravidade de Doença , Adulto Jovem
4.
Int J Cardiol ; 299: 186-191, 2020 01 15.
Artigo em Inglês | MEDLINE | ID: mdl-31303393

RESUMO

INTRODUCTION: We sought to determine prevalence and predictive accuracy of clinical markers (red flags, RF), known to be associated with specific systemic disease in a consecutive cohort of patients with hypertrophic cardiomyopathy (HCM). METHODS: We studied 129 consecutive patients (23.7 ±â€¯20.9 years, range 0-74 years; male/female 68%/32%). Pre-specified RF were categorized into five domains: family history; signs/symptoms; electrocardiography; imaging; and laboratory. Sensitivity (Se), specificity (Sp), negative predictive value (NPV), positive predictive value (PPV), and predictive accuracy of RF were analyzed in the genotyped population. RESULTS: In the overall cohort of 129 patients, 169 RF were identified in 62 patients (48%). Prevalence of RF was higher in infants (78%) and in adults >55 years old (58%). Following targeted genetic and clinical evaluation, 94 patients (74%) had a definite diagnosis (sarcomeric HCM or specific causes of HCM). We observed 14 RF in 13 patients (21%) with sarcomeric gene disease, 129 RF in 34 patients (97%) with other specific causes of HCM, and 26 RF in 15 patients (45%) with idiopathic HCM (p < 0.0001). Non-sarcomeric causes of HCM were the most prevalent in ages <1yo and > 55yo. Se, Sp, PPV, NPV and PA of RF were 97%, 70%, 55%, 98% and 77%, respectively. Single and clinical combination of RF (clusters) had an high specificity, NPV and predictive accuracy for the specific etiologies (syndromes/metabolic/infiltrative disorders associated with HCM). CONCLUSIONS: An extensive diagnostic work up, focused on analysis of specific diagnostic RF in patients with unexplained LVH facilitates a clinical diagnosis in 74% of patients with HCM.


Assuntos
Cardiomiopatia Hipertrófica/diagnóstico , Cardiomiopatia Hipertrófica/epidemiologia , Adolescente , Adulto , Idoso , Cardiomiopatia Hipertrófica/sangue , Criança , Pré-Escolar , Estudos de Coortes , Estudos Transversais , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Pessoa de Meia-Idade , Prevalência , Adulto Jovem
5.
Heart ; 106(3): 196-202, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31350276

RESUMO

OBJECTIVES: N-terminal probrain natriuretic peptide (NT-proBNP) predicts mortality and the development of heart failure in hypertrophic cardiomyopathy (HCM). Mid-regional proatrial natriuretic peptide (MR-proANP) is a stable by-product of production of atrial natriuretic peptide. We sought to compare the prognostic value of MR-proANP and NT-proBNP in HCM. METHODS: We prospectively enrolled a cohort of patients with HCM from different European centres and followed them. All patients had clinical, ECG and echocardiographic evaluation and measurement of MR-proANP and NT-proBNP at inclusion. RESULTS: Of 357 patients enrolled, the median age was 52 (IQR: 36-65) years. MR-proANP and NT-proBNP were both independently associated with age, weight, New York Heart Association (NYHA) class, left ventricular ejection fraction (LVEF), wall thickness and left atrial dimension. During a median follow-up of 23 months, 32 patients had a primary end point defined as death (n=6), heart transplantation (n=8), left ventricular assist device implantation (n=1) or heart failure hospitalisation (n=17). Both NT-proBNP and MR-proANP (p<10-4) were strongly associated with the primary endpoint, and the areas under the receiver operating characteristic (ROC) curves for both peptides were not significantly different. However, in a multiple stepwise regression analysis, the best model for predicting outcome was NYHA 1-2 vs 3-4 (HR=0.35, 95% CI 0.16 to 0.77, p<0.01), LVEF (HR=0.96, 95% CI 0.94 to 0.98, p=0.0005) and MR-proANP (HR=3.77, 95% CI 2.01 to 7.08, p<0.0001). CONCLUSIONS: MR-proANP emerges as a valuable biomarker for the prediction of death and heart failure related events in patients with HCM.


Assuntos
Fator Natriurético Atrial/sangue , Cardiomiopatia Hipertrófica/diagnóstico , Insuficiência Cardíaca/diagnóstico , Peptídeo Natriurético Encefálico/sangue , Fragmentos de Peptídeos/sangue , Adulto , Idoso , Biomarcadores/sangue , Cardiomiopatia Hipertrófica/sangue , Cardiomiopatia Hipertrófica/mortalidade , Cardiomiopatia Hipertrófica/terapia , Causas de Morte , Progressão da Doença , Europa (Continente) , Feminino , Insuficiência Cardíaca/sangue , Insuficiência Cardíaca/mortalidade , Insuficiência Cardíaca/terapia , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Prognóstico , Estudos Prospectivos , Reprodutibilidade dos Testes , Fatores de Risco , Fatores de Tempo
6.
Cardiovasc Pathol ; 43: 107150, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31639652

RESUMO

BACKGROUND: Whether current proposed biomarkers of myocardial fibrosis (BMFs) actually reflect the changes in fibrous characteristics of myocardial tissue remains unclear. The relation between peripheral BMFs and histological myocardial fibrosis in patients with hypertrophic cardiomyopathy (HCM) has been unknown. METHODS AND RESULTS: We studied 52 HCM patients who underwent a transaortic extended septal myectomy. Complete medical history was collected, and related examinations were performed. Echocardiography and cardiovascular magnetic resonance were employed to characterize cardiac morphology and function. Procollagen type I carboxy-terminal propeptide (PICP), C-terminal telopeptide of type I collagen (CITP), matrix metalloproteinases (total MMP-2 and total MMP-9), and tissue inhibitor of metalloproteinase 1 (TIMP-1) levels in both plasma and myocardial tissues were determined and compared. Myocardial fibrosis was detected with Masson's trichrome staining, and collagen volume fraction (CVF) was calculated. There was a significant correlation between plasma PICP levels and myocardial PICP contents (r=0.382, P=.007). Besides, plasma PICP (r=0.332, P=.020) levels correlated positively with CVF. In addition, plasma TIMP-1 levels were significantly correlated with myocardial TIMP-1 contents (r=0.282, P=.043). Plasma MMP-2 levels correlated positively with CVF (r=0.379, P=.006). Patients who took calcium channel blockers (CCBs; diltiazem or verapamil) had significantly lower plasma PICP levels, myocardial PICP content, and CVF in comparison with those who did not take CCBs. CONCLUSIONS: In patients with HCM, plasma PICP and MMP-2 levels quantitatively reflect myocardial fibrosis, suggesting that PICP and MMP-2 may be used as reliable BMFs. CCBs may attenuate cardiac fibrosis in patients with HCM.


Assuntos
Cardiomiopatia Hipertrófica/metabolismo , Metaloproteinase 2 da Matriz/análise , Miocárdio/química , Fragmentos de Peptídeos/análise , Pró-Colágeno/análise , Adolescente , Adulto , Idoso , Biomarcadores/análise , Biomarcadores/sangue , Cardiomiopatia Hipertrófica/sangue , Cardiomiopatia Hipertrófica/patologia , Cardiomiopatia Hipertrófica/cirurgia , Criança , Ensaio de Imunoadsorção Enzimática , Feminino , Fibrose , Humanos , Masculino , Metaloproteinase 2 da Matriz/sangue , Pessoa de Meia-Idade , Miocárdio/patologia , Fragmentos de Peptídeos/sangue , Pró-Colágeno/sangue , Adulto Jovem
7.
J Vet Cardiol ; 25: 41-51, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31568985

RESUMO

OBJECTIVES: Growth differentiation factor (GDF) 11 has been shown to reduce cardiac hypertrophy in mice. Low levels of GDF-11 are associated with cardiac hypertrophy in humans. The authors hypothesized that plasma GDF-11 level is decreased in cats with hypertrophic cardiomyopathy (HCM). Given the close homology between GDF-11 and myostatin/GDF-8, GDF-8 levels were also assessed. ANIMALS: Thirty-seven client-owned cats were enrolled, including cats with normal cardiac structure (n = 16), cats with HCM or hypertrophic obstructive cardiomyopathy (HOCM; n = 14), and cats with HCM and congestive heart failure (CHF; n = 7). METHODS: Plasma samples were analyzed for GDF-8 and GDF-11 using liquid chromatography tandem-mass spectrometry. Levels of GDF-8 and GDF-11 were compared between cats with normal cardiac structure, HCM or HOCM, and CHF. RESULTS: No differences in GDF-11 concentrations were found between cats with normal cardiac structure and cats with HCM/HOCM, with or without history of CHF. Decreased GDF-8 concentrations were detected in cats with CHF compared to cats with HCM/HOCM without history of CHF (p=0.031) and cats with normal cardiac structure (p=0.027). Growth differentiation factor 8 was higher in cats with HOCM compared to those with CHF (p=0.002). No statistical difference was noted in GDF-8 level as a function of age, weight, or body condition score. CONCLUSIONS: Plasma GDF-11 was not different between cats with HCM/HOCM and cats with normal cardiac structure regardless of age. Plasma GDF-8 was decreased in cats with CHF compared to cats with normal cardiac structure and cats with asymptomatic HCM/HOCM, suggesting a possible role in CHF development.


Assuntos
Cardiomiopatia Hipertrófica/veterinária , Doenças do Gato/sangue , Fatores de Diferenciação de Crescimento/sangue , Insuficiência Cardíaca/veterinária , Miostatina/sangue , Animais , Cardiomiopatia Hipertrófica/sangue , Cardiomiopatia Hipertrófica/complicações , Gatos , Feminino , Insuficiência Cardíaca/sangue , Insuficiência Cardíaca/etiologia , Masculino
9.
Biomark Med ; 13(14): 1175-1186, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31364861

RESUMO

Aim: The aim of the study was to investigate the monocyte count to HDL cholesterol ratio (MHR) on the prognosis of patients with hypertrophic cardiomyopathy (HCM). Materials & methods: A total of 411 patients with HCM were assessed. The primary end point was cardiovascular death or malignant arrhythmic events. Results: During the follow-up, primary end point was developed in 54 (13.1%) patients. Receiver operating characteristic (ROC) analysis showed that using a cut-off level of 14.57, MHR predicted the occurrence of primary end point with a sensitivity of 72% and specificity of 72%. In the multivariate model, high MHR was the only significant predictor of the primary end point. Conclusion: This study showed that higher MHR level is an independent predictor of malignant arrhythmia and death in patients with HCM.


Assuntos
Cardiomiopatia Hipertrófica/diagnóstico , HDL-Colesterol/sangue , Monócitos/citologia , Cardiomiopatia Hipertrófica/sangue , Cardiomiopatia Hipertrófica/imunologia , Contagem de Células , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico
10.
Dis Markers ; 2019: 6487152, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31320942

RESUMO

The aim of this study was to compare NT-proBNP using the absolute values and NT-proBNP/ULN values that were standardized by age and gender between three subgroups: those without ischemia (negative hs-troponin I and no anginal pain (hsTnI-/AP-)), those with painless ischemia (hsTnI+/AP-), and those with painful ischemia (hsTnI+/AP+). Additionally, echocardiographic parameters were compared in these three subgroups. The absolute value of NT-proBNP was significantly higher in the painful ischemia subgroup (hsTnI-/AP- vs. hsTnI+/AP- vs. hsTnI+/AP+: 502 (174-833) vs. 969 (363-1346) vs. 2053 (323-3283) pg/ml; p = 0.018 for the whole-model analysis). The standardized value of NT-proBNP/ULN was gradually increased (hsTnI-/AP- vs. hsTnI+/AP- vs. hsTnI+/AP+: 3.61 + 0.63 vs. 6.90 + 1.31 vs. 9.35 + 1.87; p = 0.001 for the whole-model analysis). In the comparison between subgroups (hsTnI-/AP- vs. hsTnI+/AP- vs. hsTnI+/AP+), two echocardiographic parameters increased significantly. The left ventricular maximum wall thickness (LVMWT) at diastole was 1.99 ± 0.08 cm vs. 2.28 ± 0.13 cm vs. 2.49 ± 0.15 cm (p = 0.004 for the whole-model analysis). The maximal gradient of the provoked left ventricular outflow tract (LVOT) gradient increased significantly in only the painful-ischemia subgroup (11 (7-30) mmHg vs. 12 (9.35-31.5) mmHg vs. 100 (43-120) mmHg). In conclusion, both painless ischemia and painful ischemia are associated with a gradual, significant increase in NT-proBNP/ULN in comparison to the double-negative hsTnI/AP subgroup. In contrast, NT-proBNP is significantly higher in only the subgroup with painful ischemia.


Assuntos
Cardiomiopatia Hipertrófica/sangue , Isquemia Miocárdica/sangue , Peptídeo Natriurético Encefálico/sangue , Fragmentos de Peptídeos/sangue , Troponina I/sangue , Disfunção Ventricular/sangue , Adulto , Biomarcadores/sangue , Cardiomiopatia Hipertrófica/diagnóstico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Isquemia Miocárdica/diagnóstico , Sensibilidade e Especificidade , Disfunção Ventricular/diagnóstico
11.
J Cardiovasc Transl Res ; 12(6): 569-579, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31278493

RESUMO

High-throughput proteomics profiling has never been applied to discover biomarkers in patients with hypertrophic cardiomyopathy (HCM). The objective was to identify plasma protein biomarkers that can distinguish HCM from controls. We performed a case-control study of patients with HCM (n = 15) and controls (n = 22). We carried out plasma proteomics profiling of 1129 proteins using the SOMAscan assay. We used the sparse partial least squares discriminant analysis to identify 50 most discriminant proteins. We also determined the area under the curve (AUC) of the receiver operating characteristic curve using the Monte Carlo cross validation with balanced subsampling. The average AUC was 0.94 (95% confidence interval, 0.82-1.00) and the discriminative accuracy was 89%. In HCM, 13 out of the 50 proteins correlated with troponin I and 12 with New York Heart Association class. Proteomics profiling can be used to elucidate protein biomarkers that distinguish HCM from controls.


Assuntos
Proteínas Sanguíneas/análise , Cardiomiopatia Hipertrófica/sangue , Proteômica , Idoso , Biomarcadores/sangue , Cardiomiopatia Hipertrófica/diagnóstico , Estudos de Casos e Controles , Feminino , Ensaios de Triagem em Larga Escala , Humanos , Análise dos Mínimos Quadrados , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Mapas de Interação de Proteínas
12.
Biomolecules ; 9(7)2019 07 13.
Artigo em Inglês | MEDLINE | ID: mdl-31337005

RESUMO

Despite genetic heterogeneity, early manifestation of diastolic dysfunction (DD) is common in hypertrophic cardiomyopathy (HCM). Nitric oxide (NO) may contribute to myocardial relaxation. NO synthases (NOS) use l-arginine (Arg) as a substrate, as asymmetric dimethylarginine (ADMA) is a direct endogenous inhibitor of NOS. This study aimed to analyze the association of Arg and its derivates, i.e., l-homoarginine (hArg), ADMA and symmetric dimethylarginine (SDMA), with DD in HCM patients. In 215 HCM patients (mean age 54 ± 15 years, 58% male) transmitral and mitral annulus velocities were echocardiographically analyzed. Plasma concentrations of Arg derivatives were measured by liquid chromatography tandem-mass spectrometry. In 143 (70%) patients suffering from DD, ADMA showed the strongest association with DD (0.66 ± 0.16, 0.72 ± 0.24, and 0.76 ± 0.26 µmol/L, p < 0.01 for trend). In linear regression analyses, positive association per standard deviation increase of ADMA was found with E-wave (beta coefficient (95% confidence interval): 4.72 (0.43-9.01); p < 0.05) and mean E/E' (1.76 (0.73-2.79) p < 0.001). Associations were adjusted for age, sex, body mass index (BMI), diabetes mellitus, coronary artery disease, and arterial hypertension. Elevated ADMA is associated with the severity of DD in HCM. Higher ADMA level might lead to decreased NO production and thus an impaired myocardial relaxation pattern.


Assuntos
Arginina/análogos & derivados , Cardiomiopatia Hipertrófica/sangue , Adulto , Idoso , Arginina/sangue , Arginina/metabolismo , Cardiomiopatia Hipertrófica/fisiopatologia , Cromatografia Líquida , Ecocardiografia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Óxido Nítrico Sintase/metabolismo , Análise de Regressão
13.
BMC Cardiovasc Disord ; 19(1): 122, 2019 05 22.
Artigo em Inglês | MEDLINE | ID: mdl-31117937

RESUMO

BACKGROUND: Postoperative atrial fibrillation (POAF) is a common complication in patients with obstructive hypertrophic cardiomyopathy (HOCM) who undergo surgical myectomy. POAF is associated with poor outcome. The role of plasma big endothelin-1 level in predicting atrial fibrillation after surgical septal myectomy in HOCM patients has not well been studied. METHODS: A total of 118 patients with HOCM who underwent surgical septal myectomy were recruited in this study. Plasma big endothelin-1 level was measured. The heart rhythm was continuously monitored during hospital stay. Preoperative, intraoperative, and postoperative variables were collected. RESULTS: POAF developed among 26 of the 118 patients (22%) in this study. Compared with those without POAF, patients with POAF were significantly older (53.5 ± 10.6 vs. 47.3 ± 13.6 years, P = 0.033), more likely to undergo mitral valve surgery (38.5% vs. 18.5%, P = 0.032), and had higher plasma big endothelin-1 levels (0.41 ± 0.19 vs. 0.27 ± 0.14 pmol/l, P = 0.001), longer hospital stay (9.1 ± 3.7 vs. 7.5 ± 2.8 days, P = 0.022), larger preoperative left atria (48.0 ± 5.2 vs. 44.1 ± 5.9 mm; P = 0.003). In the receiver operating characteristic curve analysis, the area under the curve for big endothelin-1 was 0.734 (95% CI, 0.634 to 0.834, P<0.001). In multivariate logistic regression analysis, preoperative big endothelin-1 level (OR 100.7, 95%CI: 5.0-2020.0, P = 0.003) and left atrial diameter (OR 1.106, 95%CI: 1.015-1.205, P = 0.022) were independent predictors of POAF. CONCLUSION: Elevated preoperative plasma big endothelin-1 level is an independent predictor of POAF in HOCM patients undergoing surgical septal myectomy.


Assuntos
Fibrilação Atrial/etiologia , Procedimentos Cirúrgicos Cardíacos/efeitos adversos , Cardiomiopatia Hipertrófica/cirurgia , Endotelina-1/sangue , Frequência Cardíaca , Adulto , Idoso , Fibrilação Atrial/sangue , Fibrilação Atrial/diagnóstico , Fibrilação Atrial/fisiopatologia , Biomarcadores/sangue , Cardiomiopatia Hipertrófica/sangue , Cardiomiopatia Hipertrófica/diagnóstico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento , Regulação para Cima
15.
Int Heart J ; 60(2): 327-335, 2019 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-30626765

RESUMO

Atrial fibrillation (AF) is the most common arrhythmia in patients with hypertrophic cardiomyopathy (HCM). Data regarding the correlations of biomarkers and AF in HCM patients are rather limited. We sought to explore the associations between the presence of AF and circulating biomarkers reflecting cardiovascular function (N-terminal pro-brain natriuretic peptide, NT-pro BNP), endothelial function (big endothelin-1, big ET-1), inflammation (high-sensitivity C-reactive protein), and myocardial damage (cardiac troponin I, cTnI) in HCM patients with and without left ventricular outflow tract obstruction (LVOTO).In all, 375 consecutive HCM in-hospital patients were divided into an AF group (n = 90) and a sinus rhythm (SR) group (n = 285) according to their medical history and electrocardiogram results.In comparison with the SR group, peripheral concentrations of big ET-1, NT-pro BNP, and cTnI were significantly higher in patients with AF. Only the biomarker of big ET-1, together with palpitation and left atrial diameter (LAD), was independently associated with AF in HCM patients. Ln big ET-1 was positively related to Ln NT-pro BNP, LAD, and heart rate, but negatively related to left ventricular ejection fraction. Combined measurements of big ET-1 ≥ 0.285 pmol/L and LAD ≥ 44.5 mm indicated good predictive values in the presence of AF, with a specificity of 94% and a sensitivity of 85% in HCM patients.Big ET-1 has been identified as an independent determinant of AF, regardless of LVOTO, and is significantly related to parameters representing cardiac function and remodeling in HCM. Big ET-1 might be a valuable index to evaluate the clinical status of AF in HCM patients.


Assuntos
Fibrilação Atrial/sangue , Cardiomiopatia Hipertrófica/sangue , Endotelina-1/sangue , Volume Sistólico , Obstrução do Fluxo Ventricular Externo/sangue , Remodelação Ventricular , Fibrilação Atrial/complicações , Fibrilação Atrial/diagnóstico , Biomarcadores/sangue , Proteína C-Reativa/análise , Cardiomiopatia Hipertrófica/complicações , Cardiomiopatia Hipertrófica/diagnóstico , Cardiomiopatia Hipertrófica/fisiopatologia , China , Correlação de Dados , Ecocardiografia/métodos , Eletrocardiografia/métodos , Feminino , Átrios do Coração/diagnóstico por imagem , Humanos , Masculino , Pessoa de Meia-Idade , Peptídeo Natriurético Encefálico/sangue , Fragmentos de Peptídeos/sangue , Estudos Retrospectivos , Troponina I/sangue , Obstrução do Fluxo Ventricular Externo/diagnóstico
16.
Sci Rep ; 9(1): 20350, 2019 12 30.
Artigo em Inglês | MEDLINE | ID: mdl-31889077

RESUMO

Hypertrophic cardiomyopathy (HCM) is one of the most common hereditary heart diseases and is associated with a high risk of sudden cardiac death. HCM is characterized by pronounced hypertrophy of cardiomyocytes, fiber disarray and development of fibrosis and can be divided into a non-obstructive (HNCM) and obstructive form (HOCM) therefore requiring personalized therapeutic therapies. In the present study, we investigated the expression patterns of several circulating circular RNAs (circRNAs) as potential biomarkers in patients with HCM. We included 64 patients with HCM and 53 healthy controls to the study and quantitatively measured the expression of a set of circRNAs already known to be associated with cardiac diseases (circDNAJC6) and/or being highly abundant in blood (circTMEM56 and circMBOAT2). Abundancy of circRNAs was then correlated to relevant clinical parameters. Serum expression levels of circRNAs DNAJC6, TMEM56 and MBOAT2 were downregulated in patients with HCM. The inverse association between circRNA levels and HCM remained unchanged even after adjusting for confounding factors. All circRNAs, evaluated separately or in combination, showed a robust discrimination capacity when comparing control subjects with HCM, HNCM or HOCM patients (AUC from 0.722 to 0.949). Two circRNAs, circTMEM56 and circDNAJC6, significantly negatively correlated with echocardiographic parameters for HOCM. Collectively, circulating circRNAs DNAJC6, TMEM56 and MBOAT2 can distinguish between healthy and HCM patients. In addition, circTMEM56 and circDNAJC6 could serve as indicators of disease severity in patients with HOCM. Thus, circRNAs emerge as novel biomarkers for HCM facilitating the clinical decision making in a personalized manner.


Assuntos
Cardiomiopatia Hipertrófica/diagnóstico , Cardiomiopatia Hipertrófica/genética , Ácidos Nucleicos Livres , RNA Circular/sangue , Biomarcadores , Cardiomiopatia Hipertrófica/sangue , Estudos de Casos e Controles , Ecocardiografia , Feminino , Testes de Função Cardíaca , Humanos , Masculino , Razão de Chances , Curva ROC
17.
J Physiol ; 597(5): 1337-1346, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30552684

RESUMO

KEY POINTS: Intense physical activity, a potent stimulus for sympathetic nervous system activation, is thought to increase the risk of malignant ventricular arrhythmias among patients with hypertrophic cardiomyopathy (HCM). As a result, the majority of patients with HCM deliberately reduce their habitual physical activity after diagnosis and this lifestyle change puts them at risk for sequelae of a sedentary lifestyle: weight gain, hypertension, hyperlipidaemia, insulin resistance, coronary artery disease, and increased morbidity and mortality. We show that plasma catecholamine levels remain stably low at exercise intensities below the ventilatory threshold, a parameter that can be defined during cardiopulmonary exercise testing, but rise rapidly at higher intensities of exercise. These findings suggest that cardiopulmonary exercise testing may be a useful tool to provide an individualized moderate-intensity exercise prescription for patients with HCM. ABSTRACT: Intense physical activity, a potent stimulus for sympathetic nervous system activation, is thought to increase the risk of malignant ventricular arrhythmias among patients with hypertrophic cardiomyopathy (HCM). However, the impact of exercise intensity on plasma catecholamine levels among HCM patients has not been rigorously defined. We conducted a prospective observational case-control study of men with non-obstructive HCM and age-matched controls. Laboratory-based cardiopulmonary exercise testing coupled with serial phlebotomy was used to define the relationship between exercise intensity and plasma catecholamine levels. Compared to controls (C, n = 5), HCM participants (H, n = 9) demonstrated higher left ventricular mass index (115 ± 20 vs. 90 ± 16 g/m2 , P = 0.03) and maximal left ventricular wall thickness (16 ± 1 vs. 8 ± 1 mm, P < 0.001) but similar body mass index, resting heart rate, peak oxygen consumption (H = 40 ± 13 vs. C = 42 ± 7 ml/kg/min, P = 0.81) and heart rate at the ventilatory threshold (H = 78 ± 6 vs. C = 78 ± 4% peak heart rate, P = 0.92). During incremental effort exercise in both groups, concentrations of adrenaline and noradrenaline were unchanged through low- and moderate-exercise intensity until reaching a catecholamine threshold (H = 82 ± 4 vs. C = 85 ± 3% peak heart rate, P = 0.86) after which levels of both molecules rose rapidly. In patients with mild non-obstructive HCM, plasma catecholamine levels remain stably low at exercise intensities below the ventilatory threshold but rise rapidly at higher intensities of exercise. Routine cardiopulmonary exercise testing may be a useful tool to provide an individualized moderate-intensity exercise prescription for patients with HCM.


Assuntos
Cardiomiopatia Hipertrófica/reabilitação , Epinefrina/sangue , Terapia por Exercício , Norepinefrina/sangue , Adulto , Cardiomiopatia Hipertrófica/sangue , Cardiomiopatia Hipertrófica/fisiopatologia , Exercício Físico/fisiologia , Teste de Esforço , Frequência Cardíaca , Ventrículos do Coração/fisiopatologia , Humanos , Masculino , Adulto Jovem
18.
Clin Chem Lab Med ; 57(4): 532-539, 2019 03 26.
Artigo em Inglês | MEDLINE | ID: mdl-30205637

RESUMO

Background Hypertrophic cardiomyopathy (HCM) is a serious disorder and one of the leading causes of mortality worldwide. HCM is characterized as left ventricular hypertrophy in the absence of any other loading conditions. In previous studies, mutations in at least 50 genes have been identified in HCM patients. Methods In this research, the genetic lesion of an HCM patient was identified by whole exome sequencing. Real-time polymerase chain reaction (PCR), immunofluorescence and Western blot were used to analyze the effects of the identified mutation. Results According to whole exome sequencing, we identified a de novo mutation (c.814T>C/p.F272L) of SET and MYND domain containing histone methyltransferase 1 (SMYD1) in a Chinese patient with HCM exhibiting syncope. We then generated HIS-SMYD1-pcDNA3.1+ (WT and c.814T>C/p.F272L) plasmids for transfection into AC16 cells to functionalize the mutation. The immunofluorescence experiments indicated that this mutation may block the SMYD1 protein from entering the nucleus. Both Western blot and real-time PCR revealed that, compared with cells transfected with WT plasmids, the expression of HCM-associated genes such as ß-myosin heavy chains, SMYD1 chaperones (HSP90) and downstream targets including TGF-ß were all disrupted in cells transfected with the mutant plasmid. Previous studies have demonstrated that SMYD1 plays a crucial role in sarcomere organization and heart development. Conclusions This novel mutation (c.814T>C/p.F272L) may be the first identified disease-causing mutation of SMYD1 in HCM patients worldwide. Our research expands the spectrum of HCM-causing genes and contributes to genetic counseling for HCM patients.


Assuntos
Cardiomiopatia Hipertrófica/genética , Proteínas de Ligação a DNA/genética , Proteínas Musculares/genética , Fatores de Transcrição/genética , Cardiomiopatia Hipertrófica/sangue , Proteínas de Ligação a DNA/sangue , Humanos , Masculino , Proteínas Musculares/sangue , Mutação , Fatores de Transcrição/sangue , Células Tumorais Cultivadas , Sequenciamento Completo do Exoma
19.
Herz ; 44(4): 347-353, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29147972

RESUMO

BACKGROUND: Osteopontin (OPN) is an extracellular matrix glycoprotein that plays a role in a variety of cellular activities associated with inflammatory and fibrotic responses. Increased OPN levels in myocardium and plasma have been demonstrated in patients with dilated cardiomyopathy (DCM). However, nothing is known about OPN levels in patients with hypertrophic cardiomyopathy (HCM). Therefore, the aim of our study was to compare plasma OPN levels in patients with these two most common cardiomyopathies. PATIENTS AND METHODS: We examined plasma OPN as well as creatinine, C­reactive protein (CRP), brain-type natriuretic peptide (BNP), and troponin I levels in 64 patients with DCM, 43 patients with HCM, and 75 control subjects. Transthoracic echocardiography was also performed on all cardiomyopathy patients. RESULTS: Plasma OPN levels were significantly elevated in patients with DCM compared with HCM patients (95 ± 43 vs. 57 ± 21 ng/ml; p < 0.001) and control subjects (54 ± 19 ng/ml; p < 0.001); however, there was no difference between HCM patients and control subjects. New York Heart Association (NYHA) class III or IV disease was more frequently present in DCM patients than in HCM subjects (44 % vs. 2 %, p < 0.0001). In multivariate analysis, BNP and CRP levels together with NYHA class were found to be significant predictors of plasma OPN levels in DCM patients (p = 0.002, p = 0.029, and p < 0.001 for BNP, CRP, and NYHA, respectively). CONCLUSION: Plasma OPN levels were associated with overall heart failure severity rather than with specific cardiomyopathy subtype in patients suffering from DCM or HCM, respectively.


Assuntos
Cardiomiopatia Dilatada , Cardiomiopatia Hipertrófica , Osteopontina , Cardiomiopatia Dilatada/sangue , Cardiomiopatia Hipertrófica/sangue , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Miocárdio , Peptídeo Natriurético Encefálico , Osteopontina/sangue
20.
Kardiol Pol ; 77(2): 181-189, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30566209

RESUMO

BACKGROUND: Alcohol septal ablation (ASA) is an alternative to surgical treatment in patients with hypertrophic obstructive cardiomyopathy (HOCM). Through alcohol-induced necrosis, ASA leads to an increase in left ventricular outflow tract (LVOT) diameter and a decrease in LVOT pressure gradient. AIM: We sought to assess the effect of ASA on left ventricular (LV) wall thickness and mass, left atrial (LA) size, and N-terminal pro-B-type natriuretic peptide (NT-proBNP) level. METHODS: The study cohort consisted of 50 patients with HOCM (30 in the ASA group, 20 in the optimal pharmacotherapy group [OPG]). Transthoracic echocardiography (TTE), cardiac magnetic resonance (CMR), and NT-proBNP level analysis were performed at baseline and at six months. RESULTS: All parameters are presented as means. In the ASA group, the maximal LVOT pressure gradient decreased from 122.7 to 54.8 mmHg directly after ASA and to 37.2 mmHg after a further six months (p < 0.0001). The NT-proBNP level decreased from 2174.4 to 1103.4 pg/mL (p < 0.001). On TTE, the interventricular septum (IVS) thickness decreased to from 23.6 to 19.4 mm (p < 0.0001) and the lateral wall (LW) thickness decreased from 15.9 to 14.2 mm (p < 0.007). On CMR, basal IVS thickness decreased from 23.7 to 18.0 mm (p < 0.0001) and the LW thickness decreased from 13.2 to 12.2 mm (p = 0.02). IVS mass reduced from 108.9 to 91.5 g (-16%; p < 0.001). All of the above parameters remained unchanged in the OPG. CONCLUSIONS: Successful ASA reduces LV hypertrophy and improves parameters of the LV overload, resulting in LV wall hy-pertrophy regression, and LA size and NT-proBNP level reduction. The above parameters may be as useful in assessing the efficacy of ASA as the LVOT gradient itself.


Assuntos
Técnicas de Ablação , Cardiomiopatia Hipertrófica/cirurgia , Átrios do Coração/patologia , Ventrículos do Coração/patologia , Peptídeo Natriurético Encefálico/sangue , Fragmentos de Peptídeos/sangue , Adulto , Idoso , Procedimentos Cirúrgicos Cardíacos , Cardiomiopatia Hipertrófica/sangue , Cardiomiopatia Hipertrófica/diagnóstico por imagem , Cardiomiopatia Hipertrófica/patologia , Ecocardiografia , Etanol , Feminino , Átrios do Coração/diagnóstico por imagem , Ventrículos do Coração/diagnóstico por imagem , Humanos , Hipertrofia Ventricular Esquerda , Masculino , Pessoa de Meia-Idade , Tamanho do Órgão , Estudos Prospectivos , Resultado do Tratamento
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