Katarzyna Irzyk

Refined balloon pulmonary angioplasty driven by combined assessment of intra-arterial anatomy and physiology – Multimodal approach to treated lesions in patients with non-operable distal chronic thromboembolic pulmonary hypertension – Technique, safety and efficacy of 50 consecutive angioplasties

BACKGROUND/OBJECTIVES Balloon pulmonary angioplasty (BPA) is an emerging therapeutic method in CTEPH. We aimed to prove the safety and efficacy of refined BPA driven by combined assessment of intra-arterial anatomy (IVUS/OCT) and physiology (pulmonary pressure ratio, PPR) in non-operable distal CTEPH. METHODS 11 pts (mean age 76, 59–84, 7 males) were enrolled in the BPA program according to the following inclusion criteria: 1. Non-operable CTEPH; 2. RHC with mPAP > 30 mm Hg; 3. At least one segmental perfusion defect at lung scintigraphy; 4. WHO class > II. Overall, 9 pts underwent 27 BPA sessions (mean 3 sessions per patient, range 1–5), 50 pulmonary arteries were dilated (mean 6 vessels per patient, range 3–9; 2.03 dilated arteries per session). All the angioplasties were performed according to an algorithm, which incorporated anatomical and functional assessment of targeted lesions. RESULTS We performed BPA of 32 web lesions, 5 ring-like stenosis and 13 complete obstructions. BPA resulted in clinical and hemodynamic improvement. WHO class improved from pre-BPA to post-BPA (p = 0.018), and 6 MWD increased from 304 m to 384 m (p = 0.03), NT-proBNP dropped from 1248 pg/ml to 730 pg/ml (p < 0.001). Mean PAP and PVR decreased (p = 0.01), while CO and CI increased (p = 0.01). All dilated arteries were patent at angiographic reassessment. No significant complications occurred and all treated patients are still alive. Insignificant transient reperfusion pulmonary oedema occurred in only 2 patients, who responded well to supplemental oxygen. CONCLUSIONS Refined BPA with assessment of intrapulmonary physiology using a pressure wire and precise evaluation of anatomy with IVUS and OCT provides hemodynamic and functional improvement, with minimal complications in distal non-operable CTEPH. This observation requires further validation in a large prospective study.

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.

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.

Refined balloon pulmonary angioplasty—A therapeutic option in very elderly patients with chronic thromboembolic pulmonary hypertension

INTRODUCTION/OBJECTIVES Balloon pulmonary angioplasty (BPA) is a developing treatment for inoperable chronic thromboembolic pulmonary hypertension (CTEPH). However, to our knowledge there are no published data on BPA in CTEPH subjects aged 75 or over. The aim of the study was to analyze clinical and hemodynamic outcomes of sequential BPA in very elderly patients disqualified from pulmonary endarterectomy (PEA). PATIENTS AND METHODS We enrolled 10 patients (4 male, 6 female, median age 81 [75-88]) with confirmed CTEPH, mPAP > 30 mmHg, and WHO class > II, disqualified from PEA. Overall, 10 patients underwent 39 BPA sessions (mean 3.9 sessions per patient, range 1-9), and 70 pulmonary arteries were dilated, (mean 6.5 vessels per patient, range 1-14). RESULTS Pulmonary angioplasty resulted in significant clinical and hemodynamic improvement in every patient: 6 MWT distance increased from a median of 221 m (80-320) to 345 (230-455) and plasma NT-proBNP levels decreased (P < 0.01). Sequential BPA resulted in normalization of mPAP (<25 mmHg) in 6 of 10 patients and mPAP decreased to 25-30 mmHg in three others. In the whole group mPAP decreased from 41 (31-53) mmHg to 23 (17-33) mmHg (P < 0.01). Overall, mean PAP and PVR decreased significantly in all cases, while CO and CI increased (P < 0.01). No severe complications occurred during BPA and over a median follow-up of 553 days (range 81-784), and all patients are still alive and in good general health. CONCLUSION This study demonstrated the safety and efficacy of refined BPA in CTEPH patients aged 75 or over, disqualified from PEA. Refined BPA may emerge as an alternative therapeutic strategy in very elderly CTEPH patients who are suitable for surgery, but this requires further validation in a large prospective study.

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.

High prevalence of severe coronary artery disease in elderly patients with non-operable chronic thromboembolic pulmonary hypertension referred for balloon pulmonary angioplasty

Introduction Balloon pulmonary angioplasty (BPA) is a new emerging catheter-based alternative treatment option for patients with inoperable chronic thromboembolic pulmonary hypertension (CTEPH). Aim To show that all elderly CTEPH patients referred for BPA are at higher risk of obstructive coronary artery disease and that, in daily practice, they should undergo invasive coronary angiography. Material and methods Eleven patients at the age of at least 65 years (6 males, 5 females, 77.2 ±5.9 years) with confirmed non-operable type II or type III CTEPH, considered for BPA, underwent elective coronary angiography. Severe obstructive coronary artery disease (CAD) was diagnosed when stenosis of left main coronary artery ≥ 50% or stenosis of ≥ 70% of epicardial arteries was angiographically confirmed. We also screened for CAD consecutive age- and sex-matched 114 PE survivors (52 males, 62 females, 74.8 ±7.2 years) with excluded CTEPH. Results Severe CAD was more frequent in elderly patients with non-operable type II or type III CTEPH candidates for BPA than in elderly acute PE survivors with excluded CTEPH (54.5% vs. 16.7%, p < 0.01), and therefore elderly CTEPH patients referred for BPA were at higher risk of CAD (OR = 5.9, 95% CI: 1.64–21.46, p = 0.007) when compared to elderly survivors after acute PE with excluded CTEPH. Conclusions All elderly CTEPH patients referred for BPA are at higher risk of severe CAD and should routinely undergo invasive coronary angiography before BPA.

Zmiany w układzie krążenia u pacjentów z toczniem rumieniowatym układowym

Systemic lupus erythematosus (SLE) is a systemic chronic, inflammatory, autoimmune disease, characterized by various clinical manifestations and production of multiple autoantibodies. Complex immune system dysfunctions as well as chronic inflammatory processes lead to internal organs and tissue failure. The most common cardiovascular manifestations among patients with SLE include accelerated coronary heart disease, pericarditis, myocarditis, valvular disease, Libman–Sacks nonbacterial endocarditis - the most characteristic cardiac manifestation of the SLE, conduction abnormalities, pulmonary hypertension, thromboembolic events, hypertension and heart failure. Accelerated atherosclerosis with coronary heart disease is of key importance for prognosis, particularly among young women. An increased risk of cardiovascular events among patients with SLE has been confirmed in multiple studies. Getting closer to understanding multiple mechanisms of cardiovascular disease and pathogenesis of atherosclerosis in SLE is critical to lower mortality rate in this group population. The aim of this article is to present aetiology and cardiovascular manifestations processes of SLE.