Objective The aim of this study was to evaluate cardiac autonomic nervous system function using Holter-derived and standard electrocardiographic parameters in patients with myotonic dystrophy (dystrophia myotonica, DM) and no clinically overt heart involvement. Methods Eighty-four DM patients without conditions potentially influencing cardiac autonomic function were enrolled in the study: 44 with DM type 1 and 40 with DM type 2 (mean age 34.9 +/- 11.5 and 47.8 +/- 13.5 years, respectively). Two corresponding control groups of aged-matched healthy subjects were selected for DM1 (n =3D 35) and for DM2 (n =3D 30). Standard electrocardiography for QT interval dispersion and 24-h Holter monitoring with time-domain heart rate variability and heart rate turbulence were performed. Results No significant differences in time-domain heart rate variability parameters between DM1 or DM2 subjects and controls were observed. However, heart rate turbulence parameters were significantly impaired in DM1 patients as compared to their controls: turbulence onset (p =3D 0.025), and turbulence slope (p =3D 0.018). Moreover, turbulence slope was also impaired in DM2 patients (p =3D 0.042). As compared to controls, we observed an increased QT dispersion, both in DM1 (p =3D 0.003) and also in DM2 patients (p < 0.0001). No relationship between disease duration or neurological status and time-domain heart rate variability, heart rate turbulence, and QT dispersion was observed. Interpretation Despite normal time-domain heart rate parameters, impaired heart rate turbulence and increased QT dispersion may suggest cardiac autonomic nervous system dysfunction in DM patients. The present study is the first one in which heart rate turbulence and QT dispersion assessment were examined both in DM1 and DM2 patients.

Introduction: There are limited data on left (LV) and right ventricular (RV) diastolic function in systemic sclerosis (SSc) patients especially in relation to biomarkers of matrix remodeling. The aim of the study was to analyze LV and RV myocardial diastolic function in SSc patients at baseline and after at least 1 year of follow-up and its relation to serum tissue inhibitors of metalloproteinase 1 (TIMP-1) level. Material and methods: We prospectively studied 111 SSc patients (101 female, 10 male, age 54.2+/-13.8 years) and 21 age-matched controls (18 female, 3 male, age 49.3+/-10.5 years). After at least 1 year of observation (3.0+/-1.1 years) we reevaluated 69 of the SSc patients. Transthoracic echocardiography (Philips, iE33) for assessment of LV and RV diastolic function was performed and TIMP-1 serum level was measured. Results: Impaired LV relaxation was observed in 38 (34%) SSc patients and in 1 (5%) of the controls (p < 0.001). The mean E/A ratio was lower in patients with SSc than in controls (p = 0.002) and significantly decreased after the follow-up period (p = 0.02). Impaired RV relaxation was detected in 25 (22.5%) SSc patients and in 1 (5%) control subject (p < 0.001) but did not deteriorate after follow-up. Mean serum level of TIMP-1 was significantly elevated in the follow-up group compared to baseline examination (p = 0.0001). Serum TIMP-1 level correlated positively with E/E', both septal and lateral (r = 0.4, p = 0.002 and r = 0.32, p = 0.01). Conclusions: The LV and RV relaxation is impaired in SSc patients. Moreover, left ventricular diastolic function deteriorated after the follow-up period. The TIMP-1 serum levels correlate with echocardiographic parameters, providing a potent link for LV diastolic function and matrix remodeling in patients with SSc.

To externally validate the prognostic impact of copeptin, either alone or integrated in risk stratification models, in pulmonary embolism (PE), we performed a post hoc analysis of 843 normotensive PE patients prospectively included in three European cohorts. Within the first 30 days, 21 patients (2.5%, 95% CI 1.5-3.8) had an adverse outcome and 12 (1.4%, 95% CI 0.7-2.5) died due to PE. Patients with copeptin. 24 pmol.L-1 had a 6.3-fold increased risk for an adverse outcome (95% CI 2.6-15.5, p<0.001) and a 7.6-fold increased risk for PE-related death (95% CI 2.3-25.6, p=3D0.001). Risk classification according to the 2014 European Society of Cardiology (ESC) guideline algorithm identified 248 intermediate-high-risk patients (29.4%) with 5.6% (95% CI 3.1-9.3) at risk of adverse outcomes. A stepwise biomarker-based risk assessment strategy (based on high-sensitivity troponin T, N-terminal pro-brain natriuretic peptide and copeptin) identified 123 intermediate-high-risk patients (14.6%) with 8.9% (95% CI 4.5-15.4) at risk of adverse outcomes. The identification of patients at higher risk was even better when copeptin was measured on top of the 2014 ESC algorithm in intermediate-high-risk patients (adverse outcome OR 11.1, 95% CI 4.6-27.1, p<0.001; and PE-related death OR 13.5, 95% CI 4.2-43.6, p<0.001; highest risk group versus all other risk groups). This identified 85 patients (10.1%) with 12.9% (95% CI 6.6-22.0) at risk of adverse outcomes and 8.2% (95% CI 3.4-16.2) at risk of PE-related deaths. Copeptin improves risk stratification of normotensive PE patients, especially when identifying patients with an increased risk of an adverse outcome.

Introduction: In acute pulmonary embolism (APE) the increase of pulmonary vascular resistance depends on the thromboli load and potentially on the pulmonary bed contraction caused by neurohormonal reaction. Plasma levels of endothelin were reported to be elevated in pulmonary arterial hypertension. However, there are only a few studies assessing endothelin in patients with APE.Materials & Methods: Therefore in our study we evaluated endothelin concentration in 55 patients (29M, 26F, age 57 +/- 19 yrs) with confirmed APE for potential value in risk stratification. Patients were compared with 24 healthy volunteers at similar age. On admission blood samples were collected for plasma endothelin concentration. The quantitative assessment of right ventricular (RV) function was performed by echocardiography.Results: endothelin concentrations were similar in APE patients and in control group (1.41(0.22-9.68)pg/mL vs. 1.62(0.27-8.92)pg/mL; p = NS). There was no differences in endothelin levels between APE patients with and without RV dysfunction (1.46(0.38-4.54)pg/mL vs. 1.41(0.22-9.68)pg/mL; p = NS). Endothelin concentration did not differ between patients with serious adverse events and APE group with event-free clinical course (3.19(0.38-4.27)pg/mL vs. 1.38(0.22-9.68)pg/mL; p = NS). There was no significant correlation between endothelin levels and blood saturation, time from the first symptoms, heart rate, blood pressure, tricuspid valve regurgitation pressure gradient and other echocardiographic parameters.Conclusions: We concluded that plasma endothelin concentrations assessed on admission are not elevated in patients with APE and it does not play as important role in acute phase of increase of pressure in pulmonary arteries as in chronic pulmonary hypertension. (C) 2008 Elsevier Ltd. All rights reserved.

Myocardial stretch leads to the natriuretic peptides release in acute or chronic left ventricular dysfunction. However, there is an accumulating evidence that B-type natriuretic peptide (BNP) and its N-terminal fragment (NT-proBNP) may originate from right ventricle and their concentrations elevated in patients with acute pulmonary embolism (APE) especially when resulting in right ventricular dysfunction (RVD). Recently it is underlined that severity assessment of APE as well as the risk stratification and therapy selection is based both on patients' hemodynamic status and markers of myocardial injury and RVD. BNP and NT-proBNP are helpful in identifying patients with RVD in APE, emerging as an adjunctive tool to echocardiography. Elevated BNP or NT-proBNP levels are also significant predictors of death and/or complicated clinical course in APE. (C) 2008 Elsevier B.V. All rights reserved.

Introduction: According to current ESC guidelines not only hemodynamic parameters, but also indices of right ventricular dysfunction such as NT-proBNP have a significant prognostic value in acute pulmonary embolism (PE). MR-proADM is a significant predictor of short-term mortality in acute heart failure and adds prognostic value to NT-proBNP. We hypothesized that plasma MR-proADM is elevated in acute PE, correlates with the severity of PE and has prognostic value. We also compared prognostic values of MR-proADM and NT-proBNP for the prediction of early mortality in acute PE. Material & methods: We studied 98 patients (51 F/47 M, 59.6 +/- 18.4 yr) with acute PE. On admission blood samples were collected for MR-proADM and NT-proBNP. Results: MR-proADM reflected the severity of acute PE: 0.734 nmol/L in low-risk acute PE (0.384-1.342), 0.995 nmol/L in intermediate-risk acute PE (0.394-7.499) and 2.062 nmol/L in high-risk acute PE (0.447-3.098), p < 0.001. MR-proADM was higher in non-survivors than in survivors 2.123 nmol/L (1.5434.220), vs. 0.910 nmol/L (0.384-7.449), p = 0.0003. The AUC of MR-proADM and NT-proBNP ROC curves for predicting all-cause mortality were 0.935 (95% CI 0.861-0.977) and 0.844 (95% CI 0.749-0. 913), respectively. In univariable analysis NT-proBNP and MR-proADM were significant predictors of all-cause mortality HR 1.00 (95% CI 1.000-1.0002, p = 0.029) and 1.65 (95% CI 1.214-2.249, p = 0.015). However, in multivariate analysis, MR-proADM but not NT-proBNP was a significant predictor of all-cause mortality. Conclusion: NT-proBNP and MR-proADM are of similar predictive value in the assessment of outcome in acute PE, however MR-proADM seems to be superior in predicting all-cause mortality. (c) 2013 Elsevier Ltd. All rights reserved.

Background: Early identification of high-risk individuals is key for the prevention of cardiovascular disease (CVD). The aim of this study was to assess the potential impact of a family history of metabolic syndrome (fhMetS) on the risk of metabolic disorders (abnormal body mass, lipid profile, glucose metabolism, insulin resistance, and blood pressure) in healthy young individuals. Methods: We studied CVD risk factors in 90 healthy volunteers, aged 27-39 years; of these, 78 had fhMetS and 12 were without fhMetS (control group). Fasting serum lipids, glucose, and insulin levels were assayed, and anthropometric parameters and blood pressure using, an ambulatory blood pressure monitoring system, were measured. Nutritional and physical activity habits were assessed. Results: Despite similar nutritional and physical activity habits, abnormal body mass was found in 53.2% of the fhMetS participants and 46.1% of the control participants (p = 0.54). The occurrence of obesity was 19.4% and 0%, respectively (p = 0.69). Compared to the control participants, fhMetS was associated with significantly higher total cholesterol (5.46 mmol/L vs. 4.69 mmol/L, p < 0.030), low-density lipoprotein cholesterol ( 3.28 mmol/L vs. 2.90 mmol/L, p < 0.032), and non-high-density lipoprotein cholesterol ( 3.74 mmol/L vs. 3.25 mmol/L, p < 0.016) levels, in addition to lower fasting glucose levels ( 4.51 mmol/L vs. 4.81 mmol/L, p < 0.042). A positive correlation between fasting glucose and insulin levels (r = 0.28; p < 0.015) was detected in the fhMetS participants. Higher mean daytime systolic blood pressure (121.5 mmHg vs. 113.3 mmHg, p < 0.035), mean daytime diastolic blood pressure ( 79.0 mmHg vs. 74.5 mmHg, p < 0.045), and mean nighttime diastolic blood pressure ( 64.0 mmHg vs. 59.5 mmHg, p < 0.019) were observed in the fhMetS group. Conclusions: More than 50% of the fhMetS participants had excess weight or a lipid disorder, which may indicate an increased risk of cardiovascular disease and the need for regular ambulatory assessment of serum lipid concentrations in young people with a family history of MetS.

Background Current diagnostic ECG criteria of left ventricular hypertrophy in obese patients are still lacking. Objective Methods To assess the current ECG diagnostic criteria of LVH, and to validate our previously proposed criteria in a group of patients with morbid obesity. A group of consecutive 429 obese patients (MOP) with BMI of at least 35 kg/m(2) (mean age 38.6 +/- 8.9 years, BMI 48.7 +/- 9.0 kg/m(2); 323 females, 106 males) were included. Results Conclusion The diagnosis of LVH in MOPs was confirmed only by RaVL of 7.5 mm, Cornell index of 12.5 mm; Cornell index x QRS duration of 1,125 mm x ms and Romhilt-Estes score of 1. None of the criteria proposed to date is appropriate in super-morbidly obese patients. Our study confirmed that none of the currently used voltage-based ECG criteria is appropriate for diagnosing LVH in morbidly obese patients. Further studies are required.

Elevated serum brain natriuretic peptide (BNP) released from myocytes of ventricles upon stretch have been found in patients with isolated right ventricular (RV) pressure overload. However, limited data suggest that serum BNP may be elevated in systemic sclerosis (SSc) patients, especially with RV dysfunction. We assessed serum N-terminal proBNP (NT-proBNP) in SSc and evaluated whether it reflects the severity of RV overload. We prospectively studied 51 consecutive patients (47F, mean age 53.3 +/- 15.2 years) with SSc (mean disease duration 9 +/- 12.4 years). The control group formed 31 healthy subjects (27F, mean age 52.6 +/- 12.1 years). NT-proBNP level, 6-minute walking test (6MWT), and transthoracic echocardiography (TTE) for the assessment of RV overload were performed. Serum NT-proBNP exceeded the reference value of 125 pg/mL in 31 (61%) SSc patients. The mean serum log NT-proBNP concentration in SSc was higher than in controls (2.138 +/- 0.527 vs. 1.634 +/- 0.420 pg/mL, p<0.001). 13 (25%) SSc patients have tricuspid regurgitation peak gradient (TRPG) exceeding 31 mmHg reflecting pulmonary arterial hypertension (PAH). The SSc presented other echocardiographic signs of RV overload. Mean 6MWT distance was shorter in SSc than in controls (528 +/- 100 vs. 617 +/- 80 m, p<0.001). NT-proBNP level correlated positively with TRPG, RV diameter, RV Tei index and negatively with 6MWT distance. ROC analysis identified >115 pg/ml as the best NT-proBNP threshold predicting PAH for SSc patients (sensitivity 92%, specificity 44%). Results of our study suggest that NT-proBNP measurement is a useful screening method for PAH in SSc patients. Since elevated plasma NT-proBNP level reflects the degree of right ventricular overload and limitation of exercise capacity, abnormal NT-proBNP levels should imply further evaluation including echocardiography.

OBJECTIVE: Various clinical and biochemical parameters predict the prognosis of patients with acute pulmonary embolism(APE). Treatment of APE can improve a patient's hemodynamic status, restoring adequate peripheral organ perfusion. Therefore, we hypothesized that improvement of renal function can predict short term prognosis of APE patients.; MATERIAL & METHOD: We evaluated 232 consecutive patients (94 men,aged 67 =C2=B1 18 years) with APE proven by spiral computer tomography. Blood samples were collected for creatinine assays on admission and 72 hours later, the glomerular filtration rate(eGFR) was estimated using the MDRD formula.; RESULTS: During the first 72 hours, 6 subjects died, while during the first 30 days 24(10%) subjects died (APE mortality 8%). On admission eGFR<60 ml/min was present in 113 patients(49%) and after 72 hours in 85 patients(38%). In 26 patients(11%) eGFR on admission was <60 ml/min and renal function did not improve during subsequent 72 hours. In this group the 30-day all-cause and APE-related mortality rates were 27% and 23%, respectively, while serious adverse events occurred in 38% of them. 206 patients with eGFR>60 ml/min showed a more favorable prognosis (8% 30-day all-cause mortality) than subjects with eGFR<60 ml/min and a stable eGFR during the first 72 hours (27% mortality rate, p<0.003). Persistent renal dysfunction predicted all-cause and PE-related 30-day mortality (hazard risk 2.53(CI 95%:0.96-6.68),p=3D0.06 and 3.04(CI 95%:1.28-7.26),p=3D0.01, respectively).; CONCLUSION: Approximately 50% of patients with APE have at least a moderately impaired renal function on admission. Renal function improves within 72 hours in patients with a good prognosis, while "persistent" renal dysfunction indicates an increased mortality. Copyright =C2=A9 2012 Elsevier Ltd. All rights reserved.

BACKGROUND: Heart rate turbulence (HRT) impairment is a validated and an independent indicator of cardiovascular death. There are limited data on HRT in pulmonary hypertension (PH), so we assessed potential HRT alterations in PH, especially in relation to its severity.; METHODS: Thirty-three out of 41 patients were enrolled in the study aged 49.7 =C2=B1 15.9 years (22 with arterial, 11 with chronic thromboembolic PH). Routine evaluations, right heart catheterization, and 24-hour Holter monitoring with heart rate variability and HRT assessment were performed.; RESULTS: HRT was significantly impaired in PH patients, as compared to 25 healthy controls: mean turbulence onset (TO) was -0.27% versus -2.60% (P < 0.0001), and median turbulence slope (TS) was 3.13 versus 13.5 msRR (P < 0.0001). Abnormal HRT (TO =E2=89=A5 0.0% and/or TS =E2=89=A4 2.5 ms/RR) was found in 63.3% of PH patients. Patients with PH and abnormal HRT presented more compromised functional, biochemical, and hemodynamic status than PH patients with normal TO and TS values. Multivariate stepwise regression analysis showed that TO value was related to oxygen desaturation <90% in 6-minute walking test (6-MWT; OR 0.41, P < 0.001) and was related to N-Terminal pro-B type Natriuretic Peptide concentration (OR 0.40, P < 0.001); TS was related to 6-MWT distance (OR 0.53, P < 0.0001).; CONCLUSIONS: Patients with arterial or chronic thromboembolic PH are characterized by significant impairment of HRT which is related to the disease severity. We hypothesize that patients with abnormal HRT could be considered as subjects with an increased risk of cardiovascular death, however, it needs further investigation. =C2=A9 2014 Wiley Periodicals, Inc.

d-dimer (DD) levels are used in the diagnostic workup of suspected acute pulmonary embolism (APE), but data on DD for early risk stratification in APE are limited. In this post hoc analysis of a prospective observational study of 270 consecutive patients, we aimed to optimize the discriminant capacity of the simplified pulmonary embolism severity index (sPESI), an APE risk assessment score currently used, by combining it with DD for in-hospital adverse event prediction. We found that DD levels were higher in patients with complicated versus benign clinical course 7.2 mg/L (25th-75th percentile: 4.5-27.7 mg/L) versus 5.1 mg/L (25th-75th percentile: 2.1-11.2 mg/L), P =3D .004. The area under the curve of DD for serious adverse event (SAE) was 0.672, P =3D .003. d-dimer =3D1.35 mg/L showed 100% negative predictive value for SAE and identified 11 sPESI =E2=89=A51 patients with a benign clinical course, detecting the 1 patient with SAE from sPESI =3D 0. d-dimer >15 mg/L showed heart rate for SAE 3.04 (95% confidence interval [CI]: 1-9). A stratification model which with sPESI + DD >1.35 mg/L demonstrated improved prognostic value when compared to sPESI alone (net reclassification improvement: 0.085, P =3D .04). d-dimer have prognostic value, values <1.35 mg/L identify patients with a favorable outcome, improving the prognostic potential of sPESI, while DD >15 mg/L is an independent predictor of SAE.=20

BackgroundPatients with myotonic muscular dystrophy (dystrophia myotonica, DM) are at risk of sudden cardiac death due to diverse arrhythmias, especially progressive atrioventricular (AV) conduction abnormalities. However, there are limited data on supraventricular and potentially life-threatening ventricular arrhythmias, especially according to type 1 and type 2 DM. MethodsA group of 94 unselected consecutive patients with genetically confirmed DM and 45 healthy controls underwent electrocardiography, echocardiography, and 24-hour Holter monitoring. DM1 was diagnosed in 51, while DM2 in 43 patients (with mean age of 37.3 12.5 and 48.3 13.3 years, respectively). ResultsDM1 subjects presented more frequently intraventricular conduction defects (29.4% vs 6.6%, P =3D 0.0003) and first-degree AV block (25.0% vs 4.6%, P =3D 0.008) than DM2 patients. Nonsustained supraventricular tachycardia (37.2% vs 3.8%, P =3D 0.001) and nonsustained ventricular tachycardia and/or R-on-T ventricular beats (23.2% vs 7.8%, P =3D 0.04) were more frequently observed in DM2 than in DM1. No relationship between disease duration and neurological status and occurrence of arrhythmias was observed. Multivariate analysis showed that independent predictor for bradyarrhythmias occurrence was DM1 only (odds ratio [OR] 6.4, 95% confidence interval [CI] 2.0-20.8, P =3D 0.002), while for supraventricular or ventricular arrhythmias occurrence it was DM2 (OR 4.1, 95% CI 1.5-11.4, P =3D 0.007) and increased age (OR 1.09, 95% CI 1.05-1.15, P < 0.0001). ConclusionsIn the relatively large groups of DM1 and DM2 patients, we observed frequent various arrhythmias, which warrant their close cardiac monitoring. DM1 subjects when compared to DM2 presented more frequently intraventricular and AV conduction defects. However, all types of tachyarrhythmias (except atrial fibrillation) were more frequently observed in DM2 patients.

Noncompaction of the ventricular myocardium is I recently recognized genetic cardiomyopathy. The left ventricle is the most affected site, but ventricular involvement has been reported ill some cases. Diagnosis is made with 2-dimensional echocardiography or cardiac magnetic resonance imaging. The major clinical manifestations are heart failure, arrhythmias and embolic events A 20-year old man had left and right ventricular noncompaction complicated by severe pulmonary hypertension. which is one of the first cases of biventricular noncompaction associated with severe pulmonary hypertension, Pulmonary hypertension may be a consequence of increased pulmonary venous pressures caused by systolic and diastolic heart dysfunction Secondary 10 noncompaction. (Circ J 2009, 73: 2163-2165)