The Relationship between Extracellular Volume Compartments and Matrix Metalloproteinases-2 in Left Ventricular Remodeling after Myocardial Infarction. / A Relação entre Compartimentos de Volume Extracelular e Matriz Metaloproteinase 2 na Remodelação do Ventrículo Esquerdo após o Infarto do Miocárdio.

BACKGROUND: Matrix metalloproteinases (MMPs) can affect myocardial extracellular volume (ECV) and its compartments, and this can provide more detailed information about the mechanism of adverse left ventricular (LV) remodeling (AR) after acute myocardial infarction (MI). OBJECTIVES: To investigate the role of changes (Δ) in ECV compartments (matrix volume (MVi) and cell volume (CVi)) in the development of AR after MI, and their relationship with MMP-2 expressions. METHODS: Ninety-two first MI patients who underwent 3 Tesla cardiovascular magnetic resonance imaging performed 2 weeks (baseline) and 6 months post-MI. We measured T1 mapping with MOLLI sequences. ECV was performed post-gadolinium enhancement. ECV and LV mass were used to calculate MVi and CVi. AR was defined as an increase of ≥ 12% in LV end-diastolic volume in 6 months. MMPs were measured using a bead-based multiplex immunoassay system at first day (baseline) and 2 weeks post-MI. P <0.05 was accepted as statistically significant. RESULTS: Mean ECV and mean MVi baseline levels were higher in AR group compared to without AR group (42.9±6.4 vs 39.3±8.2%, p= 0.037; 65.2±13.7 vs 56.7±14.7 mL/m2, p=0.010; respectively). CVi levels was similar between groups. A positive correlation was found between baseline levels of MMP-2 and baseline levels of ECV (r=0.535, p<0.001) and MVi (r=0.549, p<0.001). Increased ΔMVi levels was independently predictor of AR (OR=1.03, p=0.010). ΔMVi had superior diagnostic performance compared to ΔECV in predicting AR (ΔAUC: 0.215±0.07, p<0.001). CONCLUSION: High MVi levels are associated with AR, and ΔMVi was independently predictor of AR. This may be associated with MMP-2 release due to increased inflammatory response.

FUNDAMENTO: As matrizes metaloproteinases (MMPs) podem afetar o volume extracelular (VEC) e seus compartimentos, e isso pode oferecer informações mais detalhadas sobre o mecanismo de remodelação adversa (RA) do ventrículo esquerdo (VE) após o infarto agudo do miocárdio (IM). OBJETIVOS: Investigar o papel que as alterações (Δ) nos compartimentos de VEC (volume matriz (MVi) e volume celular (CVi)) desempenham no desenvolvimento de RA após o IM, e sua relação com as expressões de MMP-2. MÉTODOS: Um total de noventa e dois pacientes com primeiro IM passaram por exames de imagens por ressonância magnética cardiovascular 3 Tesla realizados 2 semanas (linha de base) e 6 meses após o IM. Medimos o mapeamento T1 com sequências MOLLI. O VEC foi obtido após o realce pelo gadolínio. O VEC e a massa do VE foram usados para calcular o MVi e o CVi. A RA foi definida como um aumento de ≥ 12% no volume diastólico final do VE em 6 meses. As MMPs foram medidas usando-se um sistema de imunoensaio multiplex em grânulos no primeiro dia (linha de base) e 2 semanas após o IM. Um P valor <0,05 foi aceito como estatisticamente significativo. RESULTADOS: Os níveis de linha de base de MVi média e VEC médio foram mais altos no grupo com RA em comparação com o grupo sem RA (42,9±6,4 vs. 39,3±8,2 %, p= 0,037; 65,2±13,7 vs. 56,7±14,7 mL/m2, p=0,010; respectivamente). Os níveis de CVi eram semelhantes entre os grupos. Foi encontrada uma correlação positiva entre os níveis de linha de base de MMP-2 e os níveis de linha de base de VEC (r=0,535, p<0,001) e MVi (r=0,549, p<0,001). O aumento dos níveis de ΔMVi foi um preditor independente da RA (RC=1,03, p=0,010). O ΔMVi teve um desempenho diagnóstico superior quando comparado ao ΔVEC na previsão do (ΔAUC: 0,215±0,07, p<0,001). CONCLUSÃO: Níveis altos de MVi estão associados à RA, e o ΔMVi foi um preditor independente de RA. Isso pode estar associado à liberação de MMP-2 devido ao aumento da resposta inflamatória.

A Relação entre Compartimentos de Volume Extracelular e Matriz Metaloproteinase 2 na Remodelação do Ventrículo Esquerdo após o Infarto do Miocárdio / The Relationship between Extracellular Volume Compartments and Matrix Metalloproteinases-2 in Left Ventricular Remodeling after Myocardial Infarction

Resumo Fundamento: As matrizes metaloproteinases (MMPs) podem afetar o volume extracelular (VEC) e seus compartimentos, e isso pode oferecer informações mais detalhadas sobre o mecanismo de remodelação adversa (RA) do ventrículo esquerdo (VE) após o infarto agudo do miocárdio (IM). Objetivos: Investigar o papel que as alterações (Δ) nos compartimentos de VEC (volume matriz (MVi) e volume celular (CVi)) desempenham no desenvolvimento de RA após o IM, e sua relação com as expressões de MMP-2. Métodos: Um total de noventa e dois pacientes com primeiro IM passaram por exames de imagens por ressonância magnética cardiovascular 3 Tesla realizados 2 semanas (linha de base) e 6 meses após o IM. Medimos o mapeamento T1 com sequências MOLLI. O VEC foi obtido após o realce pelo gadolínio. O VEC e a massa do VE foram usados para calcular o MVi e o CVi. A RA foi definida como um aumento de ≥ 12% no volume diastólico final do VE em 6 meses. As MMPs foram medidas usando-se um sistema de imunoensaio multiplex em grânulos no primeiro dia (linha de base) e 2 semanas após o IM. Um P valor <0,05 foi aceito como estatisticamente significativo. Resultados: Os níveis de linha de base de MVi média e VEC médio foram mais altos no grupo com RA em comparação com o grupo sem RA (42,9±6,4 vs. 39,3±8,2 %, p= 0,037; 65,2±13,7 vs. 56,7±14,7 mL/m2, p=0,010; respectivamente). Os níveis de CVi eram semelhantes entre os grupos. Foi encontrada uma correlação positiva entre os níveis de linha de base de MMP-2 e os níveis de linha de base de VEC (r=0,535, p<0,001) e MVi (r=0,549, p<0,001). O aumento dos níveis de ΔMVi foi um preditor independente da RA (RC=1,03, p=0,010). O ΔMVi teve um desempenho diagnóstico superior quando comparado ao ΔVEC na previsão do (ΔAUC: 0,215±0,07, p<0,001). Conclusão: Níveis altos de MVi estão associados à RA, e o ΔMVi foi um preditor independente de RA. Isso pode estar associado à liberação de MMP-2 devido ao aumento da resposta inflamatória.

Abstract Background: Matrix metalloproteinases (MMPs) can affect myocardial extracellular volume (ECV) and its compartments, and this can provide more detailed information about the mechanism of adverse left ventricular (LV) remodeling (AR) after acute myocardial infarction (MI). Objectives: To investigate the role of changes (Δ) in ECV compartments (matrix volume (MVi) and cell volume (CVi)) in the development of AR after MI, and their relationship with MMP-2 expressions. Methods: Ninety-two first MI patients who underwent 3 Tesla cardiovascular magnetic resonance imaging performed 2 weeks (baseline) and 6 months post-MI. We measured T1 mapping with MOLLI sequences. ECV was performed post-gadolinium enhancement. ECV and LV mass were used to calculate MVi and CVi. AR was defined as an increase of ≥ 12% in LV end-diastolic volume in 6 months. MMPs were measured using a bead-based multiplex immunoassay system at first day (baseline) and 2 weeks post-MI. P <0.05 was accepted as statistically significant. Results: Mean ECV and mean MVi baseline levels were higher in AR group compared to without AR group (42.9±6.4 vs 39.3±8.2%, p= 0.037; 65.2±13.7 vs 56.7±14.7 mL/m2, p=0.010; respectively). CVi levels was similar between groups. A positive correlation was found between baseline levels of MMP-2 and baseline levels of ECV (r=0.535, p<0.001) and MVi (r=0.549, p<0.001). Increased ΔMVi levels was independently predictor of AR (OR=1.03, p=0.010). ΔMVi had superior diagnostic performance compared to ΔECV in predicting AR (ΔAUC: 0.215±0.07, p<0.001). Conclusion: High MVi levels are associated with AR, and ΔMVi was independently predictor of AR. This may be associated with MMP-2 release due to increased inflammatory response.

The role of temporal changes of pro-inflammatory cytokines in the development of adverse cardiac remodeling after ST-elevation myocardial infarction.

Introduction: Increasing evidence supports the view that pro-inflammatory cytokines play a role in fibrosis after myocardial infarction (MI). It has been suggested that interleukin (IL)-12p40, a pro-inflammatory cytokine, can induce interferon γ (IFN-γ) and matrix metalloproteinase (MMP). However, the role of IL-12p40 in adverse cardiac remodeling (AR) after ST-elevation MI (STEMI) is unclear. Aim: To examine the role of temporal changes of pro-inflammatory cytokines in the development of post-STEMI AR. Material and methods: A total of 43 patients with STEMI for the first time ever were prospectively analyzed. In cardiac magnetic resonance imaging at 6 months after STEMI, a decrease of left ventricular end-diastolic volume by ≥ 12% was defined as reverse cardiac remodeling (RR), and a 12% increase was defined as AR. Cytokine concentrations were measured on the first day (baseline) and 2 weeks after STEMI. Results: Mean IL-12p40 (59.1 ±14.5 vs. 46.7 ±9.1 pq/ml, p = 0.001), median IFN-γ (20.4 vs. 16.2 pq/ml, p = 0.048) and median MMP-2 (33866 vs. 20691 pq/ml, p = 0.011) baseline concentrations were higher in AR than RR. In patients with AR, IL-12p40 level was lower at 2 weeks than baseline (p < 0.001). There was a positive correlation between the baseline concentrations of IL-12p40, IFN-γ, MMP-2, C-reactive protein and infarct size (p < 0.05). Increased IL-12p40 and MMP-2 baseline levels were independently associated with AR (OR = 1.14, p = 0.010; OR = 1.08, p = 0.035). Conclusions: In the initial phase of MI, greater release of pro-inflammatory cytokines was associated with increased MMP-2 levels. Elevated expression of IL-12 and MMP-2 had an independent association with AR. This may be related to the excessive inflammatory response in the initial phase of MI.

Copeptin levels predict left ventricular systolic function in STEMI patients: A 2D speckle tracking echocardiography-based prospective observational study.

In the present study, we aimed to investigate whether copeptin values on admission are related to left ventricle (LV) systolic function and its improvement at 6 months in ST-segment elevation myocardial infarction (STEMI) patients.In this single-center, prospective observational study, we included 122 STEMI patients from January 2016 to November 2016. LV systolic functions in the form of global longitudinal strain (GLS) in addition to conventional echocardiography parameters were evaluated on admission and at 6-month. Serum copeptin levels were determined using an ultrasensitive immunofluorescence assay.The study population was divided into 2 groups according to median values of copeptin. GLS was significantly lower in patients with high copeptin levels compared to those with low copeptin levels at early stage and 6-month (-16% (16-16.5) vs -15% (15-15.5), P < .001 and -18% (18-19) vs -16% (16-16.25), P < .001, respectively). Copeptin values were negatively correlated with an early and 6-month GLS (r = -0.459 at early stage and r = -0.662 at 6-month). In addition, we observed that copeptin values were negatively correlated with the improvement of GLS at 6-month follow-up (r = -0.458, P < .001 and r = -0.357, P = .005, respectively).Serum copeptin levels in STEMI patients at the time of admission may predict early and 6-month LV systolic function assessed by two-dimensional GLS. To the best of our knowledge, this study is the first to specifically address the relationship between copeptin values and GLS in STEMI patients.

Comparison of atrial fibrillation predictors in patients with acute coronary syndrome using ticagrelor or clopidogrel

Background/aim: Ticagrelor is a drug widely used in patients with acute coronary syndromes (ACS) that specifically increases the plasma level of adenosine, which is likely to cause atrial fibrillation (AF). Therefore, in this study we aimed to investigate the electrocardiographic and echocardiographic predictors of AF development after P2Y12 receptor antagonists in ACS patients. Materials and methods: This cross-sectional study included 831 patients with ACS (486 [58.5%] with ST elevated myocardial infarction [STEMI] and 345 [41.5%] with non-ST elevated myocardial infarction [NSTEMI]). Patients were divided into ticagrelor (n = 410) and clopidogrel (n = 421) groups. P wave properties including P wave dispersion and atrial electromechanical conduction properties were measured as AF predictors with surface ECG and tissue Doppler imaging. Results: Baseline characteristics such as age, sex, heart rate, blood pressure, and laboratory parameters were almost the same in the ticagrelor and clopidogrel groups. The statistical analysis showed no significant difference in P wave dispersion (PWD) between ticagrelor and clopidogrel groups (40.98 ± 12 ms versus 40.06 ± 12 ms, P = 0.304). Subgroups analysis according to ACS types also showed no significant difference in PWD (NSTEMI: 41.16 ± 13.8 ms versus 40.76 ± 13.55 ms, P = 0.799; STEMI: 40.9 ± 12.62 ms versus 39.19 ± 11.18 ms, P = 0.132). In addition, we did not find significant difference in atrial electromechanical delay (EMD) with tissue Doppler imaging (interatrial EMD 24.11 ± 3.06 ms versus 24.46 ± 3.23 ms, P = 0.279). Conclusion: In conclusion, we did not find any difference in detailed electrocardiographic and echocardiographic parameters as AF predictors between ticagrelor and clopidogrel groups in patients with ACS

Pulmonary Arterial Hemodynamic Assessment by a Novel Index in Systemic Sclerosis Patients: Pulmonary Pulse Transit Time.

OBJECTIVES: Systemic sclerosis (SSc) is a chronic, inflammatory, and autoimmune connective tissue disease that is associated with vascular lesions, and fibrosis of the skin and visceral organs. Cardiac complications may occur as a secondary effect of SSc as a result of pulmonary arterial hypertension and interstitial lung disease. The objective of this study was to assess whether the pulmonary pulse transit time (pPTT) could serve as a diagnostic marker for pulmonary arterial alterations in patients with SSc, prior to development of pulmonary hypertension. METHODS: Twenty-five SSc patients as a study group and 25 age- and sex-matched healthy volunteers for the control group were recruited to the study. Right ventricle function parameters, such as tricuspid annular plane systolic excursion (TAPSE), estimated pulmonary artery systolic pressure (ePASP), right ventricular dimensions, right ventricle fractional area changes, and myocardial perfusion index (MPI) were measured and calculated. Pulmonary pulse transit time was defined as the time interval between the R-wave peak in the ECG and the corresponding peak late systolic pulmonary vein flow velocity. RESULTS: Right ventricle myocardial performance index (RVMPI) and eSPAP were significantly higher in the SSc group than the controls (p = 0.032, p = 0.012, respectively). Pulmonary pulse transit time and TAPSE was shorter in the patients with SSc (p = 0.006, p = 0.015, respectively). In correlation analysis, pPTT was inversely correlated with RVMPI (r = - 0.435, p = 0.003), eSPAP (r = - 0.434, p = 0.003), and disease duration (r = - 0.595, p = 0.003). Conversely, it positively correlated with TAPSE (r = 0.345, p = 0.022). CONCLUSION: pPTT was found to be shorter in SSc patients. pPTT might serve as a surrogate marker of pulmonary hemodynamics in patients with SSc, even prior to the development of pulmonary hypertension.

Atrial fibrillation following synthetic cannabinoid abuse.

Marijuana and its synthetic forms, called synthetic cannabinoids (SCs), are used as recreational drugs. Bonzai is a kind of SC. Adverse cardiovascular events have been reported with abuse of marijuana and SCs, including arrhythmia, myocardial infarction, and sudden cardiac death. Presently described is a case of a 23-year-old, previously healthy man, who was admitted to the emergency department with atrial fibrillation after Bonzai abuse. Sinus rhythm was restored during observation.

Pulmonary arterial hemodynamic assessment by a novel index in systemic lupus erythematosus patients: pulmonary pulse transit time.

OBJECTIVE: Systemic lupus erythematosus (SLE) is a chronic, inflammatory, and autoimmune connective tissue disease. One of the leading causes of mortality among SLE patients is pulmonary hypertension. The aim of this study was to evaluate the association between echocardiographic findings, including the pulmonary pulse transit time and pulmonary hypertension parameters, in SLE patients. METHODS: Thirty SLE patients (aged 39.9±11 years, 28 females) as the study group and 34 age- and sex-matched healthy volunteers (aged 37.9±11.5 years, 31 females) as the control group were included in the study. After detailed medical histories were recorded, 12-lead electrocardiography, blood tests, and echocardiography were performed in the groups. In addition to basic echocardiographic measurements, other specialized right ventricular indicators [i.e, Tricuspid Annular Plane Systolic Excursion (TAPSE), estimated pulmonary artery systolic pressure (ePASP), right ventricular dimensions, and myocardial performance index (MPI)] were measured. The pulmonary pulse transit time was defined as the time interval between the R-wave peak in ECG and the corresponding peak late-systolic pulmonary vein flow velocity. RESULTS: The mean disease duration was 121.1±49.9 months. The mean age at diagnosis was 35.0±15.4 years. The mean RV MPI was higher (p=0.026), mean TAPSE measurements were shorter (p=0.021), and mean ePASP was higher (p=0.036) in the SLE group than in the control group. In addition, pPTT was significantly shorter in the SLE group (p=0.003). pPTT was inversely correlated with disease duration (p<0.001), MPI (p=0.037), and ePASP (p=0.02) and positively correlated with TAPSE (p<0.001). CONCLUSION: SLE patients have higher pPTT values than controls. Further, pPTT shows an inverse correlation with disease duration, MPI, and ePASP and a positive correlation with TAPSE.

Endocan and Non-Dipping Circadian Pattern in Newly Diagnosed Essential Hypertension.

BACKGROUND AND OBJECTIVES: Non-dipper hypertension is frequently accompanied by endothelial dysfunction and activation. Previous studies suggested that endocan may be a novel endothelial dysfunction marker. This study aims to investigate the association between circadian blood pressure (BP) pattern and plasma endocan levels together with high-sensitivity C-reactive protein (hsCRP) in patients with newly diagnosed untreated hypertension. SUBJECTS AND METHODS: Twenty-four hour ambulatory blood pressure monitoring was recorded in 35 dipper, 35 non-dipper hypertensives and 35 healthy controls. Endocan levels were measured by enzyme-linked immunosorbent assay. Serum levels of hsCRP were also recorded. RESULTS: Despite similar daytime and 24-hour average BP values between dippers and non-dippers, statistically significant high nocturnal BP was accompanied by a non-dipping pattern (Systolic BP: 132±9 vs. 147±11 mmHg; Distolic BP: 80±7 vs. 91±9 mmHg, respectively, p<0.001 for both). Non-dipper patients demonstrated higher endocan levels compared to dippers and normotensives (367 (193-844) pg/mL, 254 (182-512) pg/mL and 237 (141-314) pg/ml, respectively, p<0.001). HsCRP levels were significantly higher in non-dippers than the other groups (p=0.013). In a multivariate logistic regression analysis, endocan (p=0.021) and hsCRP (p=0.044) were independently associated with a non-dipping pattern. CONCLUSION: Elevated endocan levels were found in non-dipper groups. Endocan and hsCRP were found to be independently associated with a non-dipping pattern. We suggest that elevated levels of endocan in non-dipper hypertensive patients might be associated with a longer duration of exposure to high BP. These results point to the possible future role of endocan in selection of hypertensive patients at higher risk or target organ damage.