ECG in the clinical and prognostic evaluation of patients with pulmonary arterial hypertension: an underestimated value

Background: Pulmonary arterial hypertension (PAH) is a rare disease leading to right ventricular (RV) failure and manifests in decreasing exercise tolerance. Our study aimed to assess the usefulness of electrocardiographic parameters reflecting right heart hypertrophy as predictors of clinical status in PAH. Methods: The retrospective analysis included 26 patients, mean 49 ± 17 years of age, diagnosed with PAH, and eligible to undergo cardiopulmonary exercise test (CPET). The relations between ECG values and parameters obtained in procedures such as six-minute walk test (6-MWT), echocardiography, right heart catheterization (RHC), and CPET were analyzed. Results: P-wave amplitude in lead II correlated positively with CPET parameter of respiratory response: minute ventilation to carbon dioxide production slope (VE/VCO 2 slope; r  = 0.436, p  = 0.029) and echocardiographic estimated RA pressure (RAP; r  = 0.504, p  = 0.02). RV Sokolow-Lyon index (RVSLI) positively correlated with echocardiographic parameters reflecting RV function, overload, and afterload–tricuspid regurgitation pressure gradient (TRPG; r  = 0.788, p  < 0.001), RV free wall thickness ( r  = 0.738, p  < 0.001), and mean pulmonary arterial pressure (mPAP ECHO ; r  = 0.62, p  = 0.0016), respectively, as well as VE/VCO 2 slope ( r  = 0.593, p  = 0.001) and mPAP assessed directly in RHC (mPAP RHC ; r  = 0.469, p  = 0.0497). R-wave in lead aVR correlated positively with TRPG ( r  = 0.719, p  < 0.001), mPAP ECHO ( r  = 0.446, p  = 0.033), and several hemodynamic criteria of PAH diagnosis: positively with mPAP RHC ( r  = 0.505, p  = 0.033) and pulmonary vascular resistance ( r  = 0.554, p  = 0.026) and negatively with pulmonary capillary wedge pressure ( r  = −0.646, p  = 0.004). QRS duration correlated positively with estimated RAP ( r  = 0.589, p  = 0.004), vena cava inferior diameter ( r  = 0.506, p  = 0.016), and RA area ( r  = 0.679, p  = 0.002) and negatively with parameters of exercise capacity: peak VO 2 ( r  = −0.486, p  = 0.012), CPET maximum load ( r  = − 0.439, p  = 0.025), and 6-MWT distance ( r  = −0.430, p  = 0.046). ROC curves to detect intermediate/high 1-year mortality risk (based on ESC criteria) indicate RVSLI (cut-off point: 1.57 mV, AUC: 0.771) and QRS duration (cut-off points: 0.09 s, AUC: 703 and 0.1 s, AUC: 0.759) as relevant predictors. Conclusion: Electrocardiography appears to be an important and underappreciated tool in PAH assessment. ECG corresponds with clinical parameters reflecting PAH severity

Paroxysmal Atrial Fibrillation in the Course of Acute Pulmonary Embolism: Clinical Significance and Impact on Prognosis

The relationship and clinical implications of atrial fibrillation (AF) in acute pulmonary embolism (PE) are poorly investigated. We aimed to analyze clinical characteristics and prognosis in PE patients with paroxysmal AF episode. Methods. From the 391 patients with PE 31 subjects with paroxysmal AF were selected. This group was compared with patients with PE and sinus rhythm (SR) and 32 patients with PE and permanent AF. Results. Paroxysmal AF patients were the oldest. Concomitant DVT varies between groups: paroxysmal AF 32.3%, SR 49.5%, and permanent AF 28.1% (p=0.02). The stroke history frequency was 4.6% SR, 12.9% paroxysmal AF, and 21.9% permanent AF (p<0.001). Paroxysmal AF comparing to permanent AF and SR individuals had higher estimated SPAP (56 versus 48 versus 47 mmHg, p=0.01) and shorter ACT (58 versus 65 versus 70 ms, p=0.04). Patients with AF were more often classified into high-risk group according to revised Geneva score and sPESI than SR patients. In-hospital mortality was lower in SR (5%) and paroxysmal AF (6.5%) compared to permanent AF group (25%) (p<0.001). Conclusions. Patients with PE-associated paroxysmal AF constitute a separate population. More severe impairment of the parameters reflecting RV afterload may indicate relation between PE severity and paroxysmal AF episode. Paroxysmal AF has no impact on short-term mortality

Echocardiographic Assessment of Right Ventricular–Arterial Coupling in Predicting Prognosis of Pulmonary Arterial Hypertension Patients

In response to an increased afterload in pulmonary arterial hypertension (PAH), the right ventricle (RV) adapts by remodeling and increasing contractility. The idea of coupling refers to maintaining a relatively constant relationship between ventricular contractility and afterload. Twenty-eight stable PAH patients (mean age 49.5 ± 15.5 years) were enrolled into the study. The follow-up time of this study was 58 months, and the combined endpoint (CEP) was defined as death or clinical deterioration. We used echo TAPSE as a surrogate of RV contractility and estimated systolic pulmonary artery pressure (sPAP) reflecting RV afterload. Ventricular–arterial coupling was evaluated by the ratio between these two parameters (TAPSE/sPAP). In the PAH group, the mean pulmonary artery pressure (mPAP) was 47.29 ± 15.3 mmHg. The mean echo-estimated TAPSE/sPAP was 0.34 ± 0.19 mm/mmHg and was comparable in value and prognostic usefulness to the parameter derived from magnetic resonance and catheterization (ROC analysis). Patients who had CEP (n = 21) had a significantly higher mPAP (53.11 ± 17.11 mmHg vs. 34.86 ± 8.49 mmHg, p = 0.03) and lower TAPSE/sPAP (0.30 ± 0.21 vs. 0.43 ± 0.23, p = 0.04). Patients with a TAPSE/sPAP lower than 0.25 mm/mmHg had worse prognosis, with log-rank test p = 0.001. the echocardiographic estimation of TAPSE/sPAP offers an easy, reliable, non-invasive prognostic parameter for the comprehensive assessment of hemodynamic adaptation in PAH patients

Interleukin-6 signaling in patients with chronic heart failure treated with cardiac resynchronization therapy

Introduction: Increased expression of interleukin-6 (IL-6) has been described in left ventricular dysfunction in the course of chronic heart failure. Cardiac resynchronization therapy (CRT) is a unique treatment method that may reverse the course of chronic heart failure (CHF) with reduced ejection fraction (HF-REF). We aimed to evaluate the IL-6 system, including soluble IL-6 receptor (sIL-6R) and soluble glycoprotein 130 (sgp130), in HF-REF patients, with particular emphasis on CRT effects. Material and methods: The study enrolled 88 stable HF-REF patients (63.6 ±11.1 years, 12 females, EF < 35%) and 35 comorbidity-matched controls (63.5 ±9.8 years, 7 females). Forty-five HF-REF patients underwent CRT device implantation and were followed up after 6 months. Serum concentrations of IL-6, sIL-6R and sgp130 were determined using ELISA kits. Results : The HF-REF patients had higher IL-6 (median: 2.6, IQR: 1.6–3.8 vs. 2.1, IQR: 1.4–3.1 pg/ml, p = 0.03) and lower sIL-6R concentrations compared to controls (median: 51, IQR: 36–64 vs. 53. IQR 44–76 ng/ml, p = 0.008). There was no significant difference between sgp130 concentrations. In the HF-REF group IL-6 correlated negatively with EF (r = –0.5, p = 0.001) and positively with BNP (r = 0.5, p = 0.008) and CRP concentrations (r = 0.4, p = 0.02). Patients who presented a positive response after CRT showed a smaller change of sIL-6R concentration compared to nonresponders (ΔsIL-6R: –0.2 ±7.1 vs. 7 ±14 ng/ml; p = 0.04). Conclusions : HF-REF patients present higher IL-6 and lower sIL-6R levels. IL-6 concentration reflects their clinical status. CRT-related improvement of patients’ functional status is associated with a smaller change of sIL-6R concentration in time

Increased platelet content of SDF-1alpha is associated with worse prognosis in patients with pulmonary prterial hypertension

Inflammatory processes and platelet activity play an important role in the pathophysiology of pulmonary arterial hypertension (PAH). Enhanced IL-6 signaling and higher concentration of stromal-derived factor alpha (SDF-1) have been previously shown to be linked with prognosis in PAH. We hypothesized that platelets of PAH patients have higher content of IL-6 and SDF-1 and thus are involved in disease progression. We enrolled into study 22 PAH patients and 18 healthy controls. Patients with PAH presented significantly higher plasma concentrations and platelet contents of IL-6, sIL-6R, and SDF-1 than healthy subjects (platelet content normalized to protein concentration: IL-6 (0.85*10–10 [0.29 – 1.37] vs. 0.45*10–10 [0.19–0.65], sIL-6R 1.54*10–7 [1.32–2.21] vs. 1.14*10–7 [1.01–1.28] and SDF-1 (2.72*10–7 [1.85–3.23] vs. 1.70*10–7 [1.43–2.60], all p < 0.05). Patients with disease progression (death, WHO class worsening, or therapy escalation, n = 10) had a significantly higher platelet SDF-1/total platelet protein ratio (3.68*10–7 [2.45–4.62] vs. 1.69*10–7 [1.04–2.28], p = 0.001), with no significant differences between plasma levels. Kaplan–Meier analysis revealed that patients with higher platelet SDF-1/total platelet protein ratio had more frequently deterioration of PAH in the follow-up (15.24 ± 4.26 months, log-rank test, p = 0.01). Concentrations of IL-6, sIL-6 receptor and SDF-1 in plasma and platelets are elevated in PAH patients. Higher content of SDF-1 in platelets is associated with poorer prognosis. Our study, despite of limitation due to small number of enrolled patients, suggests that activated platelets may be an important source of cytokines at the site of endothelial injury, but their exact role in the pathogenesis of PAH requires further investigation

Impact of the COVID-19 pandemic on pulmonary hypertension patients : insights from the BNP-PL national database

We aimed to evaluate the clinical course and impact of the SARS-CoV-2 pandemic on the rate of diagnosis and therapy in the complete Polish population of patients (pts) with pulmonary arterial hypertension (PAH-1134) and CTEPH (570 pts) treated within the National Health Fund program and reported in the national BNP-PL database. Updated records of 1704 BNP-PL pts collected between March and December 2020 were analyzed with regard to incidence, clinical course and mortality associated with COVID-19. Clinical characteristics of the infected pts and COVID-19 decedents were analyzed. The rates of new diagnoses and treatment intensification in this period were studied and collated to the proper intervals of the previous year. The incidence of COVID-19 was 3.8% (n = 65) (PAH, 4.1%; CTEPH, 3.2%). COVID-19-related mortality was 28% (18/65 pts). Those who died were substantially older and had a more advanced functional WHO class and more cardiovascular comorbidities (comorbidity score, 4.0 ± 2.1 vs. 2.7 ± 1.8; p = 0.01). During the pandemic, annualized new diagnoses of PH diminished by 25–30% as compared to 2019. A relevant increase in total mortality was also observed among the PH pts (9.7% vs. 5.9% pre-pandemic, p = 0.006), whereas escalation of specific PAH/CTEPH therapies occurred less frequently (14.7% vs. 21.6% pre-pandemic). The COVID-19 pandemic has affected the diagnosis and treatment of PH by decreasing the number of new diagnoses, escalating therapy and enhancing overall mortality. Pulmonary hypertension is a risk factor for worsened course of COVID-19 and elevated mortality