380 Left heart disease phenotype and use of pulmonary vasodilators in elderly patients with pulmonary arterial hypertension: the Patriarca registry

Aims The prevalence of occult left heart disease (LHD) and the feasibility of vasodilator therapy in the progressively growing population of elderly subjects with pulmonary arterial hypertension (PAH) are under scrutiny. We evaluated the presence of a LHD phenotype and the patterns of vasodilator treatment in such patients. Methods and results The PATRIARCA registry collected cross-sectional data from 180 subjects with PAH or chronic thromboembolic pulmonary hypertension and ≥70 years of age in 11 Italian centres between 1 December 2019 and 15 September 2020. After excluding patients with CTEPH or incomplete follow-up haemodynamic parameters, 77 individuals with PAH diagnosed at ≥ 65 years of age according to current guidelines were included in the analysis. A LHD phenotype was defined as follows, expanding the criteria adopted in the AMBITION trial: (i) ≥3 among body mass index ≥30 kg/m2, systemic hypertension, diabetes, and significant coronary artery disease; (ii) 2 of the risk factors for LHD above and ≥1 among permanent atrial fibrillation, left ventricular (LV) hypertrophy, LV ejection fraction <50%, at least moderate mitral or aortic valve disease, and left atrial dilation; (iii) pulmonary vascular resistance (PVR) between 3 and 3.75 WU or PVR between 3.75 and 6.25 WU in the presence of a pulmonary artery wedge pressure (PAWP) of 13–15 mmHg. Forty-one (53%) patients had a LHD phenotype according to the most recent clinical and haemodynamic evaluation, which was performed 16 (4–35) months after diagnosis (Figure). As per definition, they had higher rates of comorbidities and more often echocardiographic signs of LHD (not shown). The frequency of NYHA classes I–II was comparable between the two groups, while the 6 min-walking distance tended to be lower in subjects with a LHD phenotype than in those without (Figure, left panel). Furthermore, these latter had lower PVR and higher PAWP. No differences were seen in treatment with pulmonary vasodilators, with around 50% of patients receiving double oral combination therapy in both groups (Figure, right panel). During the study period, 7 (17%) and 4 (11%) patients died in the LHD and no-LHD groups, respectively (P = 0.40). Conclusions In this real-world cohort of elderly patients, a LHD phenotype was common despite an initial haemodynamic diagnosis of PAH. However, it did not appear to cause simplification or discontinuation of pulmonary vasodilator therapy. Longitudinal studies are needed to determine whether and how a LHD phenotype affects the use and effects of PAH drugs in the elderly.

Abstract 11597: Characterization of Epinephrine Use During Extracorporeal Cardiopulmonary Resuscitation

Introduction: Guidelines recommend dosing Epinephrine (Epi) at regular intervals during pediatric cardiac arrest, including patients requiring extracorporeal membrane oxygenation (ECMO). The impact of Epi-induced vasoconstriction on systemic afterload and veno-arterial ECMO support is poorly understood. Hypothesis: Higher total dose of Epi and shorter interval between Epi dose and ECMO flow during cardiac arrest will increase systemic afterload and interfere with ECMO support. Methods: This is an ancillary study to a single-center, retrospective observational study of patients 0-18 years old who required ECMO cannulation during resuscitation over a six-year period. Patients were excluded if ECMO was initiated prior to arrest or if the resuscitation record was incomplete. The primary exposure was time from last dose of Epi to initiation of ECMO flows; secondary exposures included cumulative Epi dose delivered and indexed to arrest time. Mean arterial pressure (MAP) and systemic vasodilator therapy were used as surrogates for systemic afterload; ECMO pump speed and vasoactive-inotrope score (VIS) were used as measures of ECMO support. Results: A total 92 events in 87 patients analyzed. The patient cohort was 53% female with median (IQR) age of 122 (30-478) days, weight 4.4 (3.3 - 8.7) kg, and 43% single ventricle physiology. On average, Epi was given 7 (4 - 10) times during a 35 (27 - 44) min arrest, for a total dose of 65 (37 - 101) mcg/kg; the last dose was given 6 (2 -16) min prior to the initiation of ECMO flows. In the 6 hours following initiation of ECMO, MAP increased from 42 (36 - 56) mmHg to 57 (47 - 70) mmHg, (p<0.0001). Shorter interval between last Epi dose and ECMO initiation trended with higher MAP after 1 hour of support (estimate -0.43, p=0.06) and associated with increased of vasodilators within 6 hours of ECMO (vasodilators used (1 - 6) vs not used 9 (3 - 16) min, p=0.05). No other associations were found between Epi delivery, MAP, vasodilator use, pump speed or VIS. Conclusion: There is limited evidence to support that regular dosing of Epi throughout a cardiac arrest is associated with clinically significant increases in afterload after ECMO cannulation. Additional studies are needed to validate findings against ECMO flows and clinically relevant outcomes.

Adenosine reverses life-threatening persistent pulmonary hypertension of the neonate refractory to triple vasodilator therapy

Persistent pulmonary hypertension of the neonate can cause acute and life-threatening hypoxia, but preterm neonates are not suitable candidate to extra-corporeal life support. We report the unique case of an extremely preterm neonates with life-threatening persistent pulmonary hypertension refractory to triple vasodilator therapy (nitric oxide, iloprost, and bosentan), which has been successfully treated with the addition of adenosine continuous infusion.

Characteristics of chronic thromboembolic pulmonary hypertension in Ireland

Chronic thromboembolic pulmonary hypertension (CTEPH) is a rare and under-recognised complication of acute pulmonary embolism. Information regarding the characteristics of CTEPH in Ireland is limited, and the aim of this retrospective cohort study was to address this knowledge gap. Seventy-two cases of CTEPH were diagnosed in the National Pulmonary Hypertension Unit (NPHU) in Ireland between 2010 and 2020. This accounted for 6% of all referrals to the unit and translates to an estimated annual incidence of 1.39 per million population (95% confidence interval, 0.33–2.46). The prevalence of diagnosed CTEPH in Ireland in 2020 was estimated at 12.05 per million population (95% CI 9.00–15.10). The average duration of symptoms prior to CTEPH diagnosis was 23 (±22) months. Patients with CTEPH were more likely to be male (n = 40, 56%), older (60 ± 17 years) and have identifiable risk factors for CTEPH (n = 61, 85%) at diagnosis. Regarding treatment, pulmonary hypertension (PH) vasodilator therapy was prescribed in 75% (n = 54) within 12 months of diagnosis, inferior vena cava filters were placed in 24% (n = 17) and 97% (n = 70) of cases were anticoagulated. Pulmonary endarterectomy was performed in 35% (n = 25), balloon pulmonary angioplasty in 6% (n = 4). One-, three- and five-year survival was 93%, 80% and 65% from the time of diagnosis, and this was significantly better in patients who underwent pulmonary endarterectomy (p = 0.01). This is the first study describing the characteristics of CTEPH in Ireland and highlights suboptimal disease recognition and referral for the assessment for pulmonary endarterectomy.

Anesthesia modality does not affect clinical outcomes of intra-arterial vasodilator treatment in patients with symptomatic cerebral vasospasms

Background: Delayed cerebral ischemia and cerebral vasospasm remain the leading causes of poor outcome in survivors of aneurysmal subarachnoid hemorrhage. Refractory cerebral vasospasms can be treated with endovascular vasodilator therapy, which can either be performed in conscious sedation or general anesthesia. The aim of this study is to compare the effect of the anesthesia modality on long-term clinical outcomes in patients undergoing endovascular vasodilator therapy due to cerebral vasospasm and hypoperfusion. Methods: Modified Rankin Scale (mRS) scores were retrospectively analyzed at time of discharge from the hospital and six months after aneurysmal subarachnoid hemorrhage. Additionally, National Institutes of Health Stroke Scale (NIHSS) was assessed 24 hours before, immediately before, immediately after, and 24 hours after endovascular vasodilator therapy, and at discharge and six months. Interventional parameters such as duration of intervention, choice and dosage of vasodilator and number of arteries treated were also recorded. Results: A total of 98 patients were included in this analysis and separated into patients who had interventions in conscious sedation, general anesthesia and a mix of both. Neither mRS at discharge nor at six months showed a significant difference for functionally independent outcomes (mRS 0-2) between groups. NIHSS before endovascular vasodilator therapy was significantly higher in patients receiving interventions in general anesthesia but did not differ anymore between groups six months after the initial bleed. Conclusion: This study did not observe a difference in outcome whether patients underwent endovascular vasodilator therapy in general anesthesia or conscious sedation for refractory cerebral vasospasms. Hence, the choice should be made for each patient individually.

Changes in the Pulmonary Artery Wave Reflection in Dogs with Experimentally-Induced Acute Pulmonary Embolism and the Effect of Vasodilator

Pulmonary hypertension (PH) is a complex syndrome that has been frequently diagnosed in dogs and humans and can be detected by Doppler echocardiography and invasive catheterization. Recently, PAWR attracts much attention as a noninvasive approach for the early detection of PH. The present study aims to investigate the PAWR changes in acute pulmonary embolism (APE) and highlight the response of PAWR variables to vasodilator therapy in dogs. For this purpose, anesthesia and catheterization were performed in 6 Beagle dogs. After that, APE was experimentally conducted by Dextran microsphere administration, followed by vasodilator (Nitroprusside; 1μg/kg/min/ IV) administration. The hemodynamics, echocardiography, PVR and PAWR variables were evaluated at the baseline, after APE and after administration of nitroprusside. The result showed a significant increase in PVR, PAP, tricuspid regurgitation (TR) as well as PAWR variables following APE induction compared with the baseline (p < 0.05). Vasodilation caused by administration of nitroprusside reduced the mean atrial pressure, PVR and PAWR parameters. There were a significant correlation and linear regression between PAWR indices and PVR as well as right ventricular function parameters. In conclusion, PAWR is not only correlated with PVR but also the right ventricular function parameter, which indicates that PAWR may be useful as a new evaluation method in PH, considering that PAWR can assess both right ventricular afterload and right ventricular function.