Anna Tyrka

Pulmonary artery pulse wave velocity in idiopathic pulmonary arterial hypertension.

BACKGROUND Idiopathic pulmonary artery (PA) hypertension (IPAH) is associated with severe PA remodelling. Although the resulting increase in pulse wave velocity (PWV) might be of major pathophysiological relevance, little is known about PA-PWV in IPAH. The aim of this study was to characterize PA-PWV and its predictors in patients with IPAH. METHODS We studied 26 consecutive patients with incident IPAH aged 55.0 (45.0-66.0) years (62% female) and 10 control subjects without pulmonary hypertension. PA-PWV was measured invasively; PA wall thickness and diameter were assessed using intravascular and transthoracic ultrasonography. RESULTS PA-PWV was higher in IPAH than in control subjects (10.0 [7.5-14.0] m/s vs 3.5 [1.9-4.0] m/s; P < 0.001) as was also PA diameter and PA wall thickness. In IPAH patients, in univariate analysis PA-PWV was greater in men than in women and in patients with body mass index (BMI) < 25 kg/m(2) than with BMI ≥ 25 kg/m(2) and correlated positively with symptomatic disease duration, mean PA pressure, pulmonary vascular resistance, creatinine level, and negatively with low-density lipoprotein (LDL) cholesterol and triglyceride level but not with PA diameter or PA wall thickness. In multiple regression analysis mean PA pressure, LDL cholesterol level and BMI < 25 kg/m(2) were the main predictors of PA-PWV in IPAH patients (R(2) = 77%; P < 0.001). CONCLUSIONS PA-PWV is increased in IPAH patients. High PA pressure, low LDL cholesterol level, and BMI < 25 kg/m(2) explain most of its variability in this group.

Changes in exercise capacity and cardiac performance in a series of patients with Eisenmenger's syndrome transitioned from selective to dual endothelin receptor antagonist.

BACKGROUND Differences in clinical effects between selective and dual endothelin (ET) receptor antagonists (ERA) in patients with pulmonary arterial hypertension (PAH) are currently unknown. We aimed to assess prospectively how transition from selective (sitaxsentan) to dual (bosentan) ERA affected exercise capacity and cardiocirculatory performance in patients with Eisenmengers syndrome. METHODS A series of seven stable patients with Eisenmengers syndrome aged 40.0 (30.0-56.0) years old treated with sitaxsentan were assessed before and three months after transition to bosentan. Six minute walk test and magnetic resonance to assess LV and RV mass, volume and ejection fraction, and pulmonary flow, and laboratory tests were performed. RESULTS We observed an increase in LV mass [96.5 (66.0-116.0) vs. 123.0 (93.0-146.0)g; p=0.03], LV ejection fraction [55.0 (44.0-63.0) vs. 65.0 (58.0-70.0)%; p=0.02)], and pulmonary flow [64 (53.0-71.0) vs. 69.0 (55.0-84.0)ml/beat; p=0.046]. This was accompanied by an increase of oxygen saturation, elongation of 6MWD [435.0 (378.0-482.3) vs. 474 (405.0-534.7); p=0.02], decrease of NTproBNP level and increase of ET-1 level. CONCLUSIONS Three month follow-up of stable patients with Eisenmengers syndrome transitioned from sitaxsentan to bosentan revealed improvement of exercise capacity despite significant elevation of ET-1 level. Concurrent increase of LV ejection fraction and pulmonary flow might have contributed to these favourable effects.

Low-density lipoprotein cholesterol and survival in pulmonary arterial hypertension

Low-density lipoprotein cholesterol(LDL-C) is a well established metabolic marker of cardiovascular risk, however, its role in pulmonary arterial hypertension (PAH) has not been determined. Therefore we assessed whether LDL-C levels are altered in PAH patients, if they are associated with survival in this group and whether pulmonary hypertension (PH) reversal can influence LDL-C levels. Consecutive 46 PAH males and 94 females were age matched with a representative sample of 1168 males and 1245 females, respectively. Cox regression models were used to assess the association between LDL-C and mortality. The effect of PH reversal on LDL-C levels was assessed in 34 patients with chronic thromboembolic pulmonary hypertension (CTEPH) undergoing invasive treatment. LDL-C was lower in both PAH (2.6 ± 0.8 mmol/l) and CTEPH (2.7 ± 0.7 mmol/l) patients when compared to controls (3.2 ± 1.1 mmol/l, p < 0.001). In PAH patients lower LDL-C significantly predicted death (HR:0.44/1 mmol/l, 95%CI:0.26–0.74, p = 0.002) after a median follow-up time of 33(21–36) months. In the CTEPH group, LDL-C increased (from 2.6[2.1–3.2] to 4.0[2.8–4.9]mmol/l, p = 0.01) in patients with PH reversal but remained unchanged in other patients (2.4[2.2–2.7] vs 2.3[2.1–2.5]mmol/l, p = 0.51). We concluded that LDL-C level is low in patients with PAH and is associated with an increased risk of death. Reversal of PH increases LDL-C levels.

Mechanism and prognostic role of qR in V1 in patients with pulmonary arterial hypertension

BACKGROUND The presence of qR pattern in lead V1 of the 12-lead surface ECG has been proposed as a risk marker of death in patients with pulmonary arterial hypertension (PAH). We aimed to validate these findings in the modern era of PAH treatment and additionally to assess the relation of qR in V1 to PAH severity. We also investigated the possible mechanisms underlying this ECG sign. METHODS Consecutive patients with PAH excluding patients with congenital heart defect were recruited between February 2008 and January 2016. A 12-lead standard ECG was acquired and analyzed for the presence of qR in V1 and other potential prognostic patterns. Cardiac magnetic resonance and echocardiography were used for structural (masses and volumes) and functional (ejection fraction, eccentricity index) characterization of left (LV) and right (RV) ventricles. Standard markers of PAH severity were also assessed. RESULTS We enrolled 66 patients (19 males), aged 50.0±15.7years with idiopathic PAH (n=52) and PAH associated with connective tissue disease (n=14). qR in V1 was present in 26(39.4%) patients and was associated with worse functional capacity, hemodynamics and RV function. The main structural determinants of qR in V1 were RV to LV volume ratio (OR: 3.99; 95% CI: 1.47-10.8, p=0.007) and diastolic eccentricity index (OR: 15.0; 95% CI: 1.29-175.5, p=0.03). During observation time of 30.5±19.4months, 20 (30.3%) patient died, 13 (50%) patients with qR and 7 (17.5%) patients without qR pattern. Electrocardiographic determinants of survival were qR (HR: 3.06, 95% CI: 1.21-7.4; p=0.02) and QRS duration (HR: 1.02, 95% CI: 1.01-1.04; p=0.01). CONCLUSIONS Presence of qR in V1 reflects RV dilation and diastolic interventricular septum flattening. It is a sign of advanced PAH and predicts the risk of death in this population.

Right atrium enlargement predicts clinically significant supraventricular arrhythmia in patients with pulmonary arterial hypertension

Background: Right atrial (RA) enlargement is a common finding in patients with pulmonary arterial hypertension (PAH) and an important predictor of mortality, however its relation to the risk of atrial arrhythmias has not been assessed. Objectives: To assess whether RA enlargement is associated with supraventricular arrhythmias (SVA) and whether it predicts new clinically significant SVA (csSVA). Methods: Patients with PAH were recruited between January 2010 and December 2014 and followed until January 2017. csSVA was diagnosed if it resulted in hospitalization. To assess predictors of new csSVA, only patients without a history of SVA at baseline were analyzed. Results: Among 97 patients, any SVA was observed in 45 (46.4%) and included permanent atrial fibrillation(AF, n = 8), paroxysmal AF (n = 10), permanent atrial flutter (AFl, n = 1), paroxysmal AFl (n = 2) or other types of supraventricular tachycardia (n = 24). Patients with SVA as compared to patients without SVA were characterized by older age, lower distance in a 6‐minute test, higher NT‐proBNP, higher RA area index (RAai), left atrial area index, mean right atrial pressure (mRAP) and were more commonly treated with &bgr;‐blocker. Eighty five patients who were in sinus rhythm at baseline assessment and had no history of significant SVA were observed for 37 ± 19.9 months. During that time csSVA occurred in 15.3%. In univariate models, the occurrence of csSVA were predicted by age, right ventricular ejection fraction, right ventricular end diastolic index, RAai and mRAP, but in multivariate model only RAai remained significant predictor for csSVA (HR of 1.23, 95%CI: 1.11–1.36, p < 0.001). The optimal threshold for RA enlargement as discriminator of csSVA was 21.7 cm2/m2. Conclusions: In PAH patients RA enlargement is associated with increased prevalence of SVA. RAai is an independent predictor of hospitalization due to csSVA.

ECG Markers of Hemodynamic Improvement in Patients with Pulmonary Hypertension

Introduction Several diagnostic tests have been recommended for risk assessment in pulmonary hypertension (PH), but the role of electrocardiography (ECG) in monitoring of PH patients has not been yet established. Therefore the aim of the study was to evaluate which ECG patterns characteristic for pulmonary hypertension can predict hemodynamic improvement in patients treated with targeted therapies. Methods Consecutive patients with pulmonary arterial hypertension (PAH) or chronic thromboembolic pulmonary hypertension (CTEPH) were eligible to be included if they had had performed two consecutive right heart catheterization (RHC) procedures before and after starting of targeted therapies. Patients were followed up from June 2009 to July 2017. ECG patterns of right ventricular hypertrophy according to American College of Cardiology Foundation were assessed. Results We enrolled 80 patients with PAH and 11 patients with inoperable CTEPH. The follow-up RHC was performed within 12.6 ± 10.0 months after starting therapy. Based on median change of pulmonary vascular resistance, we divided our patients into two subgroups: with and without significant hemodynamic improvement. RV1, max⁡RV1,2 + max⁡SI,aVL − SV1, and PII improved along with the improvement of hemodynamic parameters including PVR. They predicted hemodynamic improvement with similarly good accuracy as shown in ROC analysis: RV1 (AUC: 0.75; 95% CI: 0.63–0.84), PII (AUC: 0.67, 95% CI: 0.56–0.77), and max⁡RV1,2 + max⁡SI,aVL − SV1 (0.73; 95% CI: 0.63–0.82). In Cox regression only change in RV1 remained significant mortality predictor (HR: 1.12, 95% CI: 1.01–1.24). Conclusion Electrocardiogram may be useful in predicting hemodynamic effects of targeted therapy in precapillary pulmonary hypertension. Decrease of RV1, max⁡RV1,2 + max⁡SI,aVL − SV1, and PII corresponds with hemodynamic improvement after treatment. Of these changes a decrease of R wave amplitude in V1 is associated with better survival.

Corrigendum to “ECG Markers of Hemodynamic Improvement in Patients with Pulmonary Hypertension”

[This corrects the article DOI: 10.1155/2018/4606053.].

Clinical response to calcium channel blockers in a hemodynamically unstable patient with reactive idiopathic pulmonary arterial hypertension

Acute vasoreactivity testing is indicated in patients with idiopathic pulmonary arterial hypertension (IPAH) to identify subjects who will respond favorably to long-term treatment with calcium channel blockers (CCB) [1]. The result of the test determines the choice of treatment and predicts survival of the patient [2, 3]. It has been suggested that molecular etiology of IPAH is different in patients who respond or do not respond to CCB treatment [4]. In the current guidelines [1, 5] acute va-soreactivity testing is recommended in all patients with IPAH but treatment with CCB is advised only in those in World Health Organization functional class (WHO-FC) I–III. No guidelines are provided for patients with positive acute vasoreactivity testing who are in WHO-FC IV or who are hemodynamically unstable. We present a case of a 29-year-old woman who was urgently admitted to the reference center for pulmonary hypertension from her local hospital due to rapidly progressing dyspnea and recurrent episodes of syncope. Her symptoms started 2 months before and progressed to WHO-FC IV at the time of admission. She presented with resting dyspnea, blood pressure of 90/60 mm Hg, a heart rate of 85 beats per minute and arterial blood saturation of 95%. The electrocardiogram showed sinus rhythm with an incomplete right bundle branch block. Echocardiography showed typical signs of precapillary pulmonary hypertension with right ventricular dysfunction (Table I). N-terminal pro b-type natriuretic pep-tide (NT-proBNP) was significantly elevated (Table I). On the first day of hospitalization the patient experienced syncope after minimal exertion. It was followed by prolonged hypotension which required management with intravenous fluid and continuous infusion of dobutamine. After hemodynamic stabilization, still on dobutamine, she underwent further diagnostic tests according to the current guidelines [1]. She was HIV negative ; pulmonary function tests and lung perfusion scans were normal. Abdominal USG and laboratory tests excluded liver disease. Physical examination and laboratory tests did not suggest a diagnosis of connective tissue disease. Echocardiography was negative for congenital heart disease. These results together with right heart catheterization (day 4) confirmed the diagnosis of IPAH (Table I) [6]. Acute pulmonary vasoreactivity (20 ppm of nitric oxide over 5 min) was positive. Mean pulmonary artery pressure decreased from 49 mm Hg to 26 mm Hg without a change in the cardiac index (2.1 l/min/m 2). We started treatment with amlodipine