Prevalence and clinical impact of atrioventricular conduction disease in patients with idiopathic pulmonary arterial hypertension

Background Although bradycardia-related sudden death is common in patients with idiopathic pulmonary arterial hypertension (IPAH), the prevalence and prognostic significance of atrioventricular (AV) conduction disease in this patient group is not well-established. Objectives – Determine the prevalence of AV conduction disorders in patients with IPAH – Investigate the relationship between AV block and functional outcomes and mortality. Method 12-lead electrocardiograms (ECGs) of patients with IPAH were analysed. Patients were categorised according to the presence or absence of AV block. Demographic, pulmonary haemodynamic, cardiac structural characteristics and expression of genes associated with cardiac conduction were compared and functional and mortality outcomes analysed between groups. Student's t-tests and χ2 tests were used to compare data. Survival was estimated using Kaplan-Meier analyses. Initial exploratory covariates were included in a univariate analysis and those terms with P-value of <0.1 were then used to generate a Cox proportional-hazards multivariate model. Results 135 IPAH patients (mean age 55±16 years, 28.1% male) were eligible for analysis. Median follow up was 9 years (interquartile range 4–14 years). AV block was seen in 34.8% of patients with IPAH compared to 10.8% of matched comparators (p<0.001), drawn from patients attending hospital for non-PAH related reasons. IPAH patients with conduction disease were more likely to be older (59±16 vs 53±17 years, p=0.038). AV block was associated with more severe right ventricular (RV) basal dilatation (5.1±1.0 vs 4.3±0.7cm, p=0.013) and worse RV function (fractional area change 26±9% vs 31±9%, p=0.14). Pulmonary haemodynamics, right atrial size and resting and exertional oxygen saturations were not significantly different. Expression of HCN1, HCN2, SCN1B, SCN5A, CAV1, and KCN2 genes in peripheral blood from a subcohort was similar between those with and without AV block. Lower 6 minute walk distances (344±153 vs 408±140m, p=0.035) and worse CAMPHOR scores across all 3 domains were seen in those with AV block (figure 1), and mortality was significantly higher (36.2 vs 13.6%, p=0.002) (figure 2). On multivariate analysis the presence of bundle branch block (BBB) was independently associated with a 2.1-fold increased risk of death (95% CI 1.89–4.85, p=0.045). Conclusions AV conduction disorders are more prevalent in IPAH than the general population, and are associated with worse prognosis and functional status. Prospective study is required to validate this finding. In our cohort AV block could not be explained by hypoxia, differences in pulmonary haemodynamics nor, in a small subgroup, by differential expression of specific transmembrane ion channels implicated in cardiac conduction. More detailed investigation into causal mechanisms of AV block in IPAH could establish whether improved prognosis could be achieved by treatment of AV block. FUNDunding Acknowledgement Type of funding sources: None. Figure 1 Figure 2

Pulmonary hypertension phenotypes in patients with systemic sclerosis

Pulmonary hypertension (PH) commonly affects patients with systemic sclerosis (SSc) and is associated with significant morbidity and increased mortality. PH is a heterogenous condition and several different forms can be associated with SSc, including pulmonary arterial hypertension (PAH) resulting from a pulmonary arterial vasculopathy, PH due to left heart disease and PH due to interstitial lung disease. The incidence of pulmonary veno-occlusive disease is also increased. Accurate and early diagnosis to allow optimal treatment is, therefore, essential. Recent changes to diagnostic haemodynamic criteria at the 6th World Symposium on Pulmonary Hypertension have resulted in therapeutic uncertainty regarding patients with borderline pulmonary haemodynamics. Furthermore, the optimal pulmonary vascular resistance threshold for diagnosing PAH and the role of exercise in identifying early disease require further elucidation. In this article we review the epidemiology, diagnosis, outcomes and treatment of the spectrum of pulmonary vascular phenotypes associated with SSc.

MO742PRELOAD DEPENDENCE OF PULMONARY HAEMODYNAMICS AND RIGHT VENTRICULAR PERFORMANCE: AN ECHOCARDIOGRAPHIC STUDY IN PATIENTS ON HAEMODIALYSIS

Background and Aims Haemodynamic cardiac changes in haemodialysis are associated with adverse cardiovascular outcomes and and they are difficult to measure. Systolic pulmonary artery pressure (SPAP) and right heart adaptation in relation to pre-existing preload are often disregarded. To determine volume-related changes in the pulmonary-right ventricle (RV) unit and the preload-dependence of its components, we analysed pulmonary haemodynamics and right ventricular performance, taking advantage of the plasma volume removal associated to haemodialysis (HD). Methods and results Fifty-three stable patients on chronic HD with LVEF >50% and without heart failure were recruited (mean age 63.0±12.4 years; 31.2% women; hypertension in 89% and diabetes in 53%) and evaluated just before and after HD (mean ultrafiltration volume 2.4±0.7l). SPAP from both times were available in 39 patients. After HD, SPAP decreased (42.2±12.6 to 33.7±11.6 mmHg, p<0.001) without modification of non-invasive pulmonary vascular resistance (1.75±0.44 to 1.75±0.40 eWU, p=0.94). Age and drop in the E/e’ ratio were the variables associated with greater reduction in PASP (p=0.022 and p=0.049, respectively). A significant reduction of right chamber sizes was observed, along with a diminution in measures of RV contractility, excluding RV longitudinal strain. Functional tricuspid regurgitation (FTR) diminution was observed in 26% of patients, occurring in every case with more than mild FTR. On multivariate analyses, left atrial size was the only predictor of pulmonary hypertension (defined as SPAP >40 mmHg) (OR 1.29 (1.07–1.56), p=0.006). Conclusion Rapid volemic changes determined by rapid fluid removal during hemodialysis; may affect FTR grading, RV size and contractility, with RV longitudinal strain being less variable than conventional parameters. SPAP decreases after HD, and this reduction is related to age and greater diminution of the E/e′ ratio.

Echocardiographic Evaluation of Pulmonary Haemodynamics - A Review

Pulmonary haemodynamic status has got significant clinical and prognostic significance both in structural and nonstructural heart diseases. But diagnostic accuracy depends on much care in evaluation and logical correlation of different echocardiographic parameters. Though the Doppler studies play crucial role in estimating Pulmonary haemodynamics, careful observation of 2-D measurements of different structures as well as RV systolic and diastolic function are vital issues to be addressed and correlated for diagnostic accuracy. Tricuspid Valve, RVOT and Pulmonary valve pathologies also demand vivid correlation while estimating PA pressures and pulmonary vascular resistance. Mere presence of elevated pulmonary artery systolic pressure is not enough to define pulmonary hypertension (PH). Before declaring a patient having PH a comprehensive evaluation of right heart haemodynamics is to be performed carefully to avoid unnecessary cardiac catheterization or to avoid inadvertent initiation of PH therapy. Cardiovasc. j. 2021; 13(2): 200-216

Pulmonary Hypertension in COVID-19 Pneumoniae: It Is Not Always as It Seems

A patient affected by COVID-19 pneumonia may develop pulmonary hypertension (PH) and secondary right ventricular (RV) involvement, due to lung parenchymal and interstitial damage and altered pulmonary haemodynamics, even in non-advanced phases of the disease. This is a consequence of hypoxic vasoconstriction of the pulmonary circulation, the use of positive end-expiratory pressure (PEEP) in mechanical ventilation, pulmonary endothelial injury, and local inflammatory thrombotic and/or thromboembolic processes. We report the case of a young man admitted with a diagnosis of COVID-19 pneumoniae with PH unrelated to viral infection and in whom partial anomalous pulmonary venous drainage (PAPVD) was eventually diagnosed.

Response to exercise in patients with pulmonary arterial hypertension treated with combination therapy

Pulmonary arterial hypertension (PAH) -specific combination therapy improves pulmonary haemodynamics at rest in patients with PAH; nevertheless, exertional dyspnoea remains. We investigated pulmonary haemodynamic response to exercise, and the relation to ventilatory efficiency and hypoxemia in patients with PAH treated with combination therapy. Thirty-two clinically stable patients with PAH undergoing combination therapy underwent cardiopulmonary exercise testing with right-heart catheterisation. Haemodynamic impairment was moderate-to-severe before treatment. However, it was significantly improved, and in 13 patients after treatment, the mean pulmonary arterial pressure (mPAP) at rest was <25 mmHg. The mPAP significantly increased from 27.9±10.7 to 45.9±16.7 mmHg (p<0.01) during exercise. The cardiac index increased inadequately, and the total pulmonary resistance (TPR) significantly increased from 5.74±3.42 to 6.58±3.82 Wood units (p<0.01). The mPAP/cardiac output (CO) slope was steep (10.0±6.7 mmHg·L−1·min−1). It significantly correlated with both the minute ventilation/carbon dioxide output slope (r=0.51, p<0.01) and peripheral arterial oxygen saturation/workload slope (r=−0.41, p=0.02). The mPAP/CO slope also significantly correlated with mPAP at rest (r=0.73, p<0.01) and TPR at rest (r=0.64, p<0.01). Even after pulmonary haemodynamics at rest was significantly improved in PAH patients with PAH-specific combination therapy, the mPAP/CO slope was steep and the steep mPAP/CO slope related to decreased ventilatory efficiency and the severity of hypoxemia. The mPAP/CO slope was steeper in patients with higher mPAP and TPR at rest.

Longitudinal assessment of cardiac function in infants with Down’s syndrome using novel echocardiography techniques – project protocol

Background: Down’s syndrome (DS) is the most common chromosomal abnormality globally. Ireland has one of the highest rates of DS in the western world with an incidence of 1:444 live births. Congenital heart disease (CHD) and pulmonary hypertension (PH) are the commonest morbidities affecting the cardiovascular system in DS. PH is associated with significant morbidity and an increase risk of mortality. The impact of the diagnosis of DS, the presence of CHD and the associated PH on myocardial function during transition and over the first 2 years of age in this population is not well defined and warrants further study. In particular, serial measurements of pulmonary pressures in this population over the first week of age are lacking. This study aims to characterise myocardial function and pulmonary haemodynamics in infants with Down syndrome during the transitional period (over the first week of age) and throughout the first two years of age. Methods: A prospective, observational study utilising novel echocardiography techniques to assess myocardial function and pulmonary haemodynamics over the first two years of age in infants with Down Syndrome. A population of healthy infants without CHD or a diagnosis of DS will be recruited as controls. This study will be conducted across the three Dublin maternity units. Discussion: In total, 70 babies with DS have been enrolled into this study with 292 echocardiograms performed to date. Further evaluation of cardiac performance in DS infants with and without CHD may yield more insight into the pathophysiology of cardiac dysfunction and pulmonary hypertension that are recognised features in these patients. This could aid in our ability to monitor and treat patients, as well as improve our ability to predict outcomes.