Piotr Bienias

Heart rate turbulence assessment in systemic sclerosis: the role for the detection of cardiac autonomic nervous system dysfunction

OBJECTIVE To assess the heart rate turbulence (HRT) in patients with SSc as a method of assessment for cardiac autonomic nervous function. METHODS We prospectively studied 68 consecutive patients with SSc before inclusion in the study. After a detailed clinical evaluation, including echocardiography, 45 subjects [aged 54.6 (14.7) years; 40 women] underwent 24-h Holter monitoring for HRT and time- and frequency-domain heart rate variability (HRV) assessment. Results were compared with those in 30 age- and sex-matched healthy controls. RESULTS As compared with controls, HRT was impaired in SSc patients: the median turbulence onset (TO) was higher (P = 0.0001) and the median turbulence slope (TS) was lower (P = 0.0003). Abnormal HRT (TO > or =0.0% and/or TS < or =2.5 ms/RR) was found in 42% of SSc patients. Moreover, SSc duration correlated negatively with values of TS (r = -0.3; P = 0.045). HRT did not differ between diffuse and limited SSc groups. All estimated time- and the majority of frequency-domain values of HRV parameters in SSc were significantly lower than in controls. Significant correlations were also demonstrated between HRT and HRV parameters. CONCLUSIONS HRT, like HRV assessment, indicates a frequent impairment of the cardiac autonomic nervous system in SSc patients, irrespective of the SSc type.

Antiendothelial Cells Antibodies in Patients with Systemic Sclerosis in Relation to Pulmonary Hypertension and Lung Fibrosis

Although scleroderma is generally considered a fibrosing disease, it is now recognized that the underlying vascular pathology is playing a fundamental role in its pathogenesis. The present study was aimed at testing the prevalence of anti-endothelial cell antibodies (AECA) in systemic scleroderma (SSc) patients with and without pulmonary hypertension (PH) and in relation to the presence of pulmonary fibrosis. Fifty four SSc patients (50 females and 4 male, mean age 55.7 ± 16.3 years) were prospectively screened. All patients underwent transthoracic echocardiography with the estimation of pulmonary artery pressure (PAP) and tricuspid regurgitant peak gradient (TRPG). All patients suspected to have pulmonary hypertension were referred for right heart catheterization. Restrictive lung disease was confirmed by HRCT. A healthy control group included (n = 27; 7 men and 20 women, mean age 49.8 ± 12.1 years). The study of AECA was performed using the indirect immunofluorescence method on commercially available human umbilical vein endothelial cells. The HRCT scans in patients with suspected interstitial lung disease revealed signs of lung fibrosis in 15 (out of the 36 examined patients). TRPG at rest of 31 mmHg was demonstrated in 14 (21%) patients. During cardiac catheterization, arterial PH was found in two patients. Resting venous PH was found in one patient and an excessive post capillary PAP elevation at rest was demonstrated in 11 patients. At the baseline, 14/54 patients (26%) were positive for AECA. In the control group, the frequency of the antibodies was 3/27 (11%). No statistical correlation between antibody titter and the presentation of the disease existed. AECA were highly prevalent in a subgroup of patients suffering from interstitial pulmonary fibrosis. Out of the 15 patients suffering from lung fibrosis, 7 were AECA positive. The presence of AECA correlated very well with antinuclear antibodies (ANA), but was not related to the profile of ANA. Our findings support evidence that endothelial cell damage is involved in SSc, as there was increased prevalence of circulating AECA of the IgG isotype in SSc patients. AECA may also be related to the complications of SSc, like pulmonary fibrosis.

Electrocardiographic criteria of left ventricular hypertrophy in patients with morbid obesity.

Background: Obesity is frequently accompanied by systemic hypertension complicated by left ventricular hypertrophy (LVH). Standard electrocardiography (ECG) is generally accepted screening tool for LVH in systemic hypertension. The aim was to assess currently used ECG criteria in the diagnosis of LVH in morbidly obese patients.

Heart rate turbulence impairment and ventricular arrhythmias in patients with systemic sclerosis.

Background:  Arrhythmias, conduction disturbances, and cardiac autonomic nervous system dysfunction are the most frequent cardiovascular complications in systemic sclerosis (scleroderma). The aim of the study was to assess heart rate turbulence (HRT) in systemic sclerosis patients and to identify the relationship between HRT and occurrence of arrhythmias.

Andersen–Tawil syndrome: Report of 3 novel mutations and high risk of symptomatic cardiac involvement

Introduction: Andersen–Tawil syndrome (ATS) is a potassium channelopathy affecting cardiac and skeletal muscle. Periodic paralysis is a presenting symptom in some patients, whereas, in others, symptomatic arrhythmias or prolongation of QT in echocardiographic recordings will lead to diagnosis of ATS. Striking intrafamilial variability of expression of KCNJ2 mutations and rarity of the syndrome may lead to misdiagnosis. Methods: We report 15 patients from 8 Polish families with ATS, including 3 with novel KCNJ2 mutations. Results: All patients had dysmorphic features; periodic paralysis affected males more frequently than females (80% vs. 20%), and most attacks were normokalemic. Two patients (with T75M and T309I mutations) had aborted sudden cardiac death. An implantable cardioverter‐defibrillator was utilized in 40% of cases. Conclusions: KCNJ2 mutations cause a variable phenotype, with dysmorphic features seen in all patients studied, a high penetrance of periodic paralysis in males and ventricular arrhythmia with a risk of sudden cardiac death. Muscle Nerve 51: 192–196, 2015

Heart diastolic dysfunction in patients with systemic sclerosis

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.

Supraventricular and Ventricular Arrhythmias Are Related to the Type of Myotonic Dystrophy but Not to Disease Duration or Neurological Status.

Patients 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.

Tricuspid annulus plane systolic excursion (TAPSE) has superior predictive value compared to right ventricular to left ventricular ratio in normotensive patients with acute pulmonary embolism

Introduction Right ventricular dysfunction (RVD) is an indicator of poor prognosis in normotensive patients with acute pulmonary embolism (APE). The aim of this study was to compare right ventricular (RV)/left ventricular (LV) ratio measured by echocardiography and multidetector computed tomography (MDCT) with tricuspid annulus plane systolic excursion (TAPSE) as a prognostic factor of APE-related 30-day mortality. Material and methods We examined 76 patients with confirmed APE, hemodynamically stable at admission. We evaluated the prognostic value of RV/LV ratio in the apical 4-chamber view and TAPSE measured at echocardiography and the MDCT RV/LV ratio. Results Thirty-day APE-related mortality was 10.5% (8 patients). The area under the curve (AUC) for TAPSE in the prediction of APE-related mortality was higher (p < 0.00001) (0.905, 95% CI: 0.828–0.983) than the AUC of the echo RV/LV ratio (0.427, 95% CI: 0.183–0.672) and MDCT RV/LV ratio (0.371, 95% CI: 0.145–0.598). In univariable Cox analysis, TAPSE was the only significant mortality predictor, with hazard ratio (HR) 0.73 (95% CI: 0.62–0.87, p = 0.0004). In multivariable Cox analysis TAPSE was the only significant mortality predictor, with HR 0.62 (95% CI: 0.46–0.85; p = 0.003), while age, heart rate, and RV/LV ratio in echo or MDCT were non-significant. TAPSE ≤ 15 mm was a significant predictor of APE-related mortality, with HR 26.2 (95% CI: 3.2–214.1; p = 0.002), PPV 44% and NPV 98%. Conclusions The TAPSE is preferable to echo and MDCT RV/LV ratio for risk stratification in initially normotensive patients with APE. The TAPSE ≤ 15 mm identifies patients with an increased risk of 30-day APE-related mortality.

Assessment of systemic and pulmonary arterial remodelling in women with systemic sclerosis.

Objectives: Systemic sclerosis (SSc) leads to pulmonary circulation dysfunctionand there are some indications of systemic circulation impairment. We evaluated the influence of SSc on the elastic properties of large systemic arterial walls and potential correlations between systemic and pulmonary circulation involvement. Method: We examined 75 consecutive women (mean age 53.13 ± 10.1 years) with confirmed SSc [mean disease duration (DD) 7.1 ± 9.1 years] and 21 age-matched female volunteers (mean age 52.6 ± 8.3 years, ns). Pulse wave velocity (PWV) and transthoracic echocardiography were performed. SSc patients were divided into two groups according to the median of DD: ≤ 3 years (39 patients) and > 3 years (36 patients). Results: Patients with DD > 3 years had higher PWV than those with DD ≤ 3 years and controls (log PWV: 2.23 ± 0.23 vs. 2.13 ± 0.16 and vs. 2.11 ± 0.16 m/s; p = 0.028 and 0.029, respectively). In addition, echocardiographic indices showed impaired right ventricular (RV) function in the patients with DD > 3 years. Also in these SSc patients, PWV correlated with clinical and echocardiographic parameters of pulmonary circulation: age (r = 0.64, p < 0.0001), acceleration time of pulmonary ejection (AcT; r = −0.38, p = 0.021), and tricuspid regurgitation peak gradient (TRPG; r = 0.34, p = 0.04). Multiple linear regression analysis showed that PWV was independently associated with DD (β = 0.22, p = = 0.02), AcT (β = −0.215, p = 0.03), and age (β = 0.44, p < 0.001). Conclusions: In patients with SSc lasting more than 3 years, the disease is characterized by increased stiffness of the large systemic arteries. Longer duration of SSc leads simultaneously to the increased stiffness of the large systemic arteries and to the progressive impairment of RV function and its coupling to the pulmonary arterial bed.

Pro- and antiangiogenic markers in patients with pulmonary complications of systemic scleroderma.

Systemic sclerosis (SSc) is an autoimmune disorder characterized by skin and internal organs fibrosis and concomitant vascular abnormalities. Although SSc is considered mainly fibrosing disease, underlying vascular pathology plays a fundamental role in its pathogenesis. We have focused on positive and negative serum markers of angiogenesis and fibrosis (pigment epithelium-derived factor [PEDF], vascular endothelial growth factor [VEGF], and soluble VEGF receptor [sVEGFR]), in progressive SSc patients at baseline and after follow-up in relation to cardiopulmonary complications (systemic hypertension [HT], pulmonary arterial hypertension [PAH] and pulmonary fibrosis [PF]). VEGF and PEDF but not sVEGFR were reciprocally regulated in SSc progression. Moreover, VEGF/PEDF ratio significantly increased during follow up suggesting that it might be used as a biomarker of disease progression. No correlation between the studied markers and cardiopulmonary complications was observed. In conclusion, VEGF and PEDF level, and the VEGF/PEDF ratio are significantly changed in the course of SSc progression and these markers can be used to assess SSc activity.