Decrease In Pulmonary Vascular Resistance Research Articles

Balloon pulmonary angioplasty in patients with chronic thromboembolic pulmonary hypertension: short- and long-term results from a cohort in Brazil.

A significant number of patients with chronic thromboembolic pulmonary hypertension (CTEPH) are not eligible for pulmonary endarterectomy and may be treated with balloon pulmonary angioplasty (BPA). Although BPA programs have recently been developed in Brazil, no results have yet been published. The objective of this study was to assess the clinical and hemodynamic progression of the first patients treated with BPA at our center. This was an observational study of 23 patients with CTEPH enrolled in the BPA program of a specialized center in Brazil between 2015 and 2020. After a mean of 5.6 ± 1.3 sessions and 11 ± 2.8 treated segments/patient (at a mean of 6.7 ± 2.9 months post-BPA), there was a 26% decrease in mean pulmonary artery pressure (51 ± 11 vs. 38 ± 11 mmHg; p < 0.0001), a 43% decrease in pulmonary vascular resistance (10 ± 3.7 vs. 5.7 ± 3.3 WU; p < 0.0001), and a 22.5% increase in the cardiac index (2.38 ± 0.6 vs. 2.95 ± 0.6 L/min/m2; p < 0.0001). There was an increase in the six-minute walk distance and an improvement in functional class. Acute lung injury with clinical manifestations was observed after 7% of the BPA sessions. None of the patients required intubation. During a mean outpatient follow-up period of 38 ± 22 months, two patients were referred for additional BPA sessions due to clinical worsening and new hospitalizations. Two deaths were recorded (due to CTEPH progression and gastrointestinal bleeding, respectively). Among this first group of patients treated with BPA in Brazil, there was significant short- and long-term clinical improvement, together with a low frequency of complications.

Phosphodiesterase 9A inhibition improves aging-related increase in pulmonary vascular resistance in mice.

As individuals age, there is a gradual decline in cardiopulmonary function, often accompanied by cardiac pump dysfunction leading to increased pulmonary vascular resistance (PVR). Our study aims to investigate the changes in cardiac and pulmonary vascular function associated with aging. Additionally, we aim to explore the impact of phosphodiesterase 9A (PDE9A) inhibition, which has shown promise in treating cardiometabolic diseases, on addressing left ventricle (LV) dysfunction and elevated PVR in aging individuals. Young (3 months old) and aged (32 months old) male C57BL/6 mice were used. Aged mice were treated with the selective PDE9A inhibitor PF04447943 (1 mg/kg/day) through intraperitoneal injections for 10 days. LV function was evaluated using cardiac ultrasound, and PVR was assessed in isolated, ventilated lungs perfused under a constant flow condition. Additionally, changes in PVR were measured in response to perfusion of the endothelium-dependent agonist bradykinin or to nitric oxide (NO) donor sodium nitroprusside (SNP). PDE9A protein expression was measured by Western blots. Our results demonstrate the development of LV diastolic dysfunction and increased PVR in aged mice. The aged mice exhibited diminished decreases in PVR in response to both bradykinin and SNP compared to the young mice. Moreover, the lungs of aged mice showed an increase in PDE9A protein expression. Treatment of aged mice with PF04447943 had no significant effect on LV systolic or diastolic function. However, PF04447943 treatment normalized PVR and SNP-induced responses, though it did not affect the bradykinin response. These data demonstrate a development of LV diastolic dysfunction and increase in PVR in aged mice. We propose that inhibitors of PDE9A could represent a novel therapeutic approach to specifically prevent aging-related pulmonary dysfunction.

Effect of Acute Vasodilator Testing Using Oxygen in Pulmonary Hypertension Due to Left Heart Disease.

Pulmonary vasodilators, including oxygen, have not shown consistent beneficial effects on pulmonary hypertension due to valvular heart disease (PH-VHD). Therefore, the study aimed to assess the effect of 100% fractional inspiration of oxygen (FiO2) on pulmonary and systemic hemodynamics in patients with combined pre- and post-capillary pulmonary hypertension (CpcPH) and isolated post-capillary pulmonary hypertension (IpcPH) due to PH-VHD. This prospective study was conducted among patients with PH-VHD undergoing mitral or aortic valve replacement or repair. The study was conducted after induction of anesthesia and pulmonary artery catheterization. Cardiac output was obtained using thermodilution and all direct, and derived hemodynamic variables were obtained at 30% and 100% FiO2. The patients were stratified a priori into responders {(≥10mmHg fall in mean pulmonary artery pressure (MPAP)} and non-responders. Fifty-seven patients completed the acute vasodilator test. The mean age and body mass index of the study population was 41.8 ± 14.1years and 21.4 ± 4.6kg/m2, respectively. There was a significant decrease in MPAP (40.77 ± 12.07mmHg vs 36.74 ± 13.3mmHg; P < .001) and pulmonary vascular resistance (PVR) {(median; Interquartile range (IQR); 388; 371 vs 323; 362dynes sec.cm-5; P < .001) at 100% FiO2. Transpulmonary gradient (TPG) and diastolic pulmonary gradient (DPG) also decreased significantly (P < .001 and P < .001). Cardiac output did not change significantly. The magnitude of decrease in MPAP, PVR, TPG, DPG, and pulmonary artery compliance (PAC) between CpcPH and IpcPH was comparable. Responders did not show a significantly greater fall in MPAP, PVR, TPG, DPG, and PAC after surgery. Hyperoxia may lead to reduction in MPAP and PVR in both hemodynamic phenotypes of PH-VHD. A larger sample size is required to support or refute the findings of this study.

Younger age at initiation of subcutaneous treprostinil is associated with better response in pediatric Group 1 pulmonary arterial hypertension.

Children with severe Group 1 pulmonary arterial hypertension (PAH) have an unpredictable response to subcutaneous treprostinil (TRE) therapy, which may be influenced by age, disease severity, or other unknown variables at time of initiation. In this retrospective single-center cohort study, we hypothesized that younger age at TRE initiation, early hemodynamic response (a decrease in pulmonary vascular resistance by ≥30% at follow-up catheterization), and less severe baseline hemodynamics (Rp:Rs < 1.1) would each be associated with better clinical outcomes. In 40 pediatric patients with Group I PAH aged 17 days-18 years treated with subcutaneous TRE, younger age (cut-off of 6-years of age, AUC 0.824) at TRE initiation was associated with superior 5-year freedom from adverse events (94% vs. 39%, p = 0.002), better WHO functional class (I or II: 88% vs. 39% p = 0.003), and better echocardiographic indices of right ventricular function at most recent follow-up. Neither early hemodynamic response nor less severe baseline hemodynamics were associated with better outcomes. Patients who did not have a significant early hemodynamic response to TRE by first follow-up catheterization were unlikely to show subsequent improvement in PVRi (1/8, 13%). These findings may help clinicians counsel families and guide clinical decision making regarding the timing of advanced therapies.

Hemodynamic response to inhaled nitric oxide in patients with pulmonary hypertension and chronic kidney disease: A retrospective cohort study.

Pulmonary hypertension (PH) associated with chronic kidney disease (CKD) (PH-CKD) affects approximately 20%-40% of CKD patients and is associated with increased morbidity and mortality. PH and CKD are both pathophysiologically associated with nitric oxide (NO) deficiency. The NO pathway, an important therapeutic domain in pulmonary arterial hypertension (PAH), is an intriguing but unexplored target in PH-CKD. We sought to improve understanding of the clinical significance of the NO pathway in patients with PH-CKD by assessing the hemodynamic response to inhaled NO (iNO) during right heart catheterization (RHC). In this retrospective cohort study, patients with diagnosis codes of PH and stage IV/V CKD or end-stage renal disease and estimated glomerular filtration rate < 60 mL/min/body surface areawho underwent RHC and hemodynamic drug study between July 2011 and June 2021 were eligible. Patients with mean pulmonary artery pressure (mPAP) > 20 mmHg and pulmonary vascular resistance (PVR) > 3Wood unitswere included. The final cohort included 37 patients (45.9% female, mean age 72.5 ± 9.7 years). A total of 56.7%of the cohort (21/37) had precapillary PH, while 43.2% (16/37) had combined precapillary postcapillary PH (Cpc-PH). Median survival was 3.1 years after RHC. iNO was associated with a significant decrease in both mPAP and PVR. Hemodynamic changes in mPAP and PVR were similar in precapillary and Cpc-PH groups. Among a small subset (n = 14) who were subsequently treated with PAH-targeted therapy, treatment response was mixed and did not reveal significant benefit. Further studies are warranted to better define the potential role of PAH therapy in PH-CKD.

Acute Hemodynamics in the Fontan Circulation: Open-Label Study of Vasopressin.

To describe the acute hemodynamic effect of vasopressin on the Fontan circulation, including systemic and pulmonary pressures and resistances, left atrial pressure, and cardiac index. Prospective, open-label, nonrandomized study (NCT04463394). Cardiac catheterization laboratory at Lucile Packard Children's Hospital, Stanford. Patients 3-50 years old with a Fontan circulation who were referred to the cardiac catheterization laboratory for hemodynamic assessment and/or intervention. A 0.03 U/kg IV (maximum dose 1 unit) bolus of vasopressin was administered over 5 minutes, followed by a maintenance infusion of 0.3 mU/kg/min (maximum dose 0.03 U/min). Comprehensive cardiac catheterization measurements before and after vasopressin administration. Measurements included pulmonary artery, atrial, and systemic arterial pressures, oxygen saturations, and systemic and pulmonary flows and resistances. There were 28 patients studied. Median age was 13.5 (9.1, 17) years, and 16 (57%) patients had a single or dominant right ventricle. Following vasopressin administration, systolic blood pressure and systemic vascular resistance (SVR) increased by 17.5 (13.0, 22.8) mm Hg ( Z value -4.6, p < 0.001) and 3.8 (1.8, 7.5) Wood Units ( Z value -4.6, p < 0.001), respectively. The pulmonary vascular resistance (PVR) decreased by 0.4 ± 0.4 WU ( t statistic 6.2, p < 0.001), and the left atrial pressure increased by 1.0 (0.0, 2.0) mm Hg ( Z value -3.5, p < 0.001). The PVR:SVR decreased by 0.04 ± 0.03 ( t statistic 8.1, p < 0.001). Neither the pulmonary artery pressure (median difference 0.0 [-1.0, 1.0], Z value -0.4, p = 0.69) nor cardiac index (0.1 ± 0.3, t statistic -1.4, p = 0.18) changed significantly. There were no adverse events. In Fontan patients undergoing cardiac catheterization, vasopressin administration resulted in a significant increase in systolic blood pressure, SVR, and left atrial pressure, decrease in PVR, and no change in cardiac index or pulmonary artery pressure. These findings suggest that in Fontan patients vasopressin may be an option for treating systemic hypotension during sedation or general anesthesia.

Normothermic &lt;i&gt;ex vivo&lt;/i&gt; lung perfusion using a developed solution followed by orthotopic left lung transplantation (experimental study)

The continued unavailability of adequate organs for transplantation to meet the existing demand has resulted in a major challenge in transplantology. This is especially felt in lung transplantation (LTx). LTx is the only effective method of treatment for patients with end-stage lung diseases. Normothermic ex vivo lung perfusion (EVLP) has been proposed to increase the number of donor organs suitable for transplant – EVLP has proven itself in a number of clinical trials. The ability to restore suboptimal donor lungs, previously considered unsuitable for transplantation, can improve organ functionality, and thus increase the number of lung transplants. However, widespread implementation of ex vivo perfusion is associated with high financial costs for consumables and perfusate.Objective: to test the developed solution on an ex vivo lung perfusion model, followed by orthotopic LT under experimental conditions.Materials and methods. The experiment included lung explantation stages, static hypothermic storage, EVLP and orthotopic left LTx. Perfusion was performed in a closed perfusion system. We used our own made human albumin-based perfusion solution as perfusate. Perfusion lasted for 2 hours, and evaluation was carried out every 30 minutes. In all cases, static hypothermic storage after perfusion lasted for 4 hours. The orthotopic single-lung transplantation procedure was performed using assisted circulation, supplemented by membrane oxygenation. Postoperative follow-up was 2 hours, after which the experimental animal was euthanized.Results. Respiratory index before lung explantation was 310 ± 40 mmHg. The PaO2/FiO2 ratio had positive growth dynamics throughout the entire EVLP procedure. Oxygenation index was 437 ± 25 mm Hg after 120 minutes of perfusion. Throughout the entire EVLP procedure, there was a steady decrease in pulmonary vascular resistance (PVR). Initial PVR was 300 ± 100 dyn×s/cm5; throughout the EVLP, PVR tended to fall, reaching 38,5 ± 12 dyn×s/cm5 at the end of perfusion.Conclusion. A safe and effective EVLP using our perfusate is possible. The developed orthotopic left lung transplantation protocol under circulatory support conditions, supplemented by membrane oxygenation, showed it is efficient and reliable.

Anomalous origin of the left main coronary artery from the right pulmonary artery: a case report

Anomalous origin of the left coronary from the right pulmonary artery (AOLCARPA) is an extremely rare anomaly, which has been reported in only a few patients worldwide [1] An 8-month-old male patient weighing 5.7 kg came to our hospital with chief complaints of tachypnea while feeding and failure to thrive. ECG of the patient showed sinus tachycardia. The patient had a heart rate of 140/min and saturation of 99% on room air. Chest radiograph showed cardiomegaly. Transthoracic echocardiography showed moderate mitral regurgitation, dilated left atrium and ventricle, severe left ventricular (LV) dysfunction, global LV hypokinesia with an LV ejection fraction of 15–20%. Flow pattern in the left anterior descending artery and the left circumflex artery was reversed and the right coronary artery (RCA) was dilated. The left main coronary artery (LMCA) origin was not clear. As the diagnosis was unclear, computed tomography coronary angiography (CTCA) was done to delineate the coronary anatomy, which showed an anomalous origin of LMCA from the right pulmonary artery (RPA) (Figs. 1 and 2Figs 1, 2). Blood investigations including complete blood count, and liver and kidney function tests were normal. Preoperative medication of the patient included digoxin, spironolactone, furosemide, and milrinone infusion. The patient was posted for corrective repair of anomalous origin of the left coronary artery from the RPA.Figure 1: Computed tomography coronary angiography showing left main coronary artery (LMCA) arising from the right pulmonary artery (RPA). PROX LAD, proximal left anterior descending artery.Figure 2: (a) Midesophageal (ME) ascending aortic short-axis (SAX) view showing retrograde flow from left main coronary artery (LMCA) to right pulmonary artery (RPA). (b) Midesophageal (ME) four-chamber view showing dilated left ventricle (LV) and mitral regurgitation jet. (c) Origin of LMCA from RPA. LPA, left pulmonary artery; Asc Aorta, ascending aorta.On the day of surgery, the patient was taken to the operating room. Preoperative inotropic support of intravenous infusion of milrinone 0.5 µg/kg/min was continued. After attaching a multiparameter monitor with a five-lead ECG, noninvasive blood pressure monitor, and a pulse oximeter, general anesthesia was induced with intravenous fentanyl 2 µg/kg, midazolam 0.1 mg/kg, vecuronium 0.1 mg/kg, and endotracheal intubation was done. Femoral artery was cannulated for invasive arterial blood pressure monitoring, and central venous catheter was inserted in the right internal jugular vein. Anesthesia was maintained with isoflurane and intermittent boluses of fentanyl and vecuronium. Intraoperative ventilation was instituted with the goals of avoiding hypocarbia, hyperoxia, and alkalosis. An FiO2 of 0.35 was kept with PaO2 targets of 80–100 mm Hg to maintain pulmonary vascular resistance End-tidal carbon dioxide (EtCO2) was maintained between 40 and 42 mm Hg. Pre-bypass transesophageal echocardiography (TOE) examination was carried out with a pediatric 9T probe (Vivid I, GE; Vingmed Ultrasound, Horten, Norway). ME ascending aorta short-axis view showed the origin of LMCA from RPA (Fig. 2a). Midesophageal four-chamber view showed dilated LV and moderate mitral regurgitation (Fig. 2b). Heparin 400 IU/kg was given, and cardiopulmonary bypass was instituted. Cardiopulmonary bypass was established using aortobicaval cannulation with looping of both pulmonary artery branches. Myocardial preservation was obtained with antegrade cold blood potassium cardioplegia into the aorta and main pulmonary artery. Under low pump flows, LMCA origin was identified originating from the RPA (Fig. 2c). Medial trap door was made in the aorta and LMCA was anastomosed to the aorta (coronary translocation). Posterior annuloplasty of the mitral valve was performed through the trans-septal approach. Weaning from the cardiopulmonary bypass was uneventful with minimal inotropic support (milrinone 0.5 µg/kg/min; Epinephrine 0.04 µg/kg/min). The chest was kept open with a sterile membrane cover electively and the patient was shifted to the pediatric ICU with stable hemodynamics. AOLCARPA is an extremely rare congenital coronary anomaly. Only 10–20% of neonates survive till adulthood, and it depends on the adequacy of LV perfusion through collaterals to LCA from RCA and the proportion of coronary steal from the LCA to pulmonary artery [2] Coronary angiogram is usually done to delineate the anatomy and for the diagnosis. In this case, the origin of LMCA could not be visualized on transthoracic echocardiography (TTE) leading to inconclusive diagnosis. CTCA delineated the exact anatomy and showed its origin from RPA. Intraoperative TOE examination also revealed it as a case of AOLCARPA. Anesthetic management of patients presenting with ALOCARPA includes rapid and smooth intubation, while avoiding swings in blood pressure and heart rate. A decrease in pulmonary vascular resistance is avoided by preventing hyperventilation, hyperoxia and hypocarbia [3] The aim is to maintain a PaO2 of 80–100 mm Hg and an EtCO2 of 40–45 mm Hg. Both reduction and increase in afterload can hamper RCA perfusion and stroke volume, respectively. An optimum preload is required to ensure adequate cardiac output. CTCA and TOE examinations are useful modalities for delineating the coronary anatomy and help in planning the perioperative surgical and anesthetic management of the patient.

121 RELEVANCE OF COMORBIDITIES ON INITIAL COMBINATION THERAPY IN PULMONARY ARTERIAL HYPERTENSION

Abstract Rationale Demographic characteristics of pulmonary arterial hypertension (PAH) patients have changed over time, but the effects of cardiovascular risk factors on risk status and pulmonary vascular resistance (PVR) reduction with initial oral combination therapy are not known. Therefore, we tested the relevance of cardiovascular comorbidities in this setting. Methods The study enrolled 181 treatment-naive PAH patients with a 6- months (IQR 144-363 days) right heart catheterization and risk assessment after initial oral combination therapy. Results Group-A, 96 (53.0%) patients without cardiac comorbidities; Group-B, 54 (29.8%) patients with one cardiac comorbidity; Group-C, 31 (17.1%) patients with ≥2 cardiac comorbidities. Group-C patients were older with a balanced gender distribution. There was a significant difference in PVR reduction moving from the absence to one or ≥2 cardiac comorbidities, respectively, median -45.0%, -30.3%, -24.3%. A ERS/ESC low-risk status was present at first follow-up in 50 (52.0%) patients in Group-A, 19 (35.1%) in Group-B, and 9 (29.0%) in Group-C; a REVEAL 2.0 low-risk status was present at first follow-up in 41 (42.0%) patients in Group-A, 15 (27.7%) in Group-B, and 7 (22.6%) in Group-C. Group-A patients were 2.3 times more likely to achieve/maintain a low risk status compared with Group-B and -C (OR 2.27, 95% C.I. 1.15-4.54, p=0.02). No significant difference was observed between patients with non-cardiac comorbidities and those without comorbidities. Conclusion Initial oral combination therapy seems associated with a less effective response for patients with cardiovascular comorbidities compared with the others, related to the magnitude of treatment- induced decrease in PVR.

Pulmonary vascular reactivity to supplemental oxygen in Sherpa and lowlanders during gradual ascent to high altitude.

What is the central question of this study? How does hypoxic pulmonary vasoconstriction and the response to supplemental oxygen change over time at high altitude? What is the main finding and its importance? Lowlanders and partially de-acclimatized Sherpa both demonstrated pulmonary vascular responsiveness to supplemental oxygen that was maintained for 12days' exposure to progressively increasing altitude. An additional 2 weeks' acclimatization at 5050m altitude rendered the pulmonary vasculature minimally responsive to oxygen similar to the fully acclimatized non-ascent Sherpa. Additional hypoxic exposure at that time point did not augment hypoxic pulmonary vasoconstriction. Prolonged alveolar hypoxia leads to pulmonary vascular remodelling. We examined the time course at altitude, over which hypoxic pulmonary vasoconstriction goes from being acutely reversible to potentially irreversible. Study subjects were lowlanders (n=20) and two Sherpa groups. All Sherpa were born and raised at altitude. One group (ascent Sherpa, n=11) left altitude and after de-acclimatization in Kathmandu for ∼7days re-ascended with the lowlanders over 8-10days to 5050m. The second Sherpa group (non-ascent Sherpa, n=12) remained continuously at altitude. Pulmonary artery systolic pressure (PASP) and pulmonary vascular resistance (PVR) were measured while breathing ambient air and following supplemental oxygen. During ascent PASP and PVR increased in lowlanders and ascent Sherpa; however, with supplemental oxygen, lowlanders had significantly greater decrease in PASP (P=0.02) and PVR (P=0.02). After ∼14days at 5050m, PASP decreased with supplemental oxygen (mean decrease: 3.9mmHg, 95% CI 2.1-5.7mmHg, P<0.001); however, PVR was unchanged (P=0.49). In conclusion, PASP and PVR increased with gradual ascent to altitude and decreased via oxygen supplementation in both lowlanders and ascent Sherpa. Following ∼14days at 5050m altitude, there was no change in PVR to hypoxia or O2 supplementation in lowlanders or either Sherpa group. These data show that both duration of exposure and residential altitude influence the pulmonary vascular responses to hypoxia.

Efficacy and safety of balloon pulmonary angioplasty for patients with chronic thromboembolic pulmonary hypertension comorbid to chronic obstructive pulmonary disease

Abstract Background Balloon pulmonary angioplasty (BPA) would be promising treatment option for non-operable chronic thromboembolic pulmonary hypertension (CTEPH). However, BPA for CTEPH with Chronic obstructive pulmonary disease (COPD) might exacerbate ventilation perfusion mismatch. The aim is to evaluate the efficacy and safety of BPA for CTEPH with moderate or severe COPD. Method Data from 149 CTEPH patients were collected retrospectively who underwent BPA from March 2011 to June 2021. Patients were divided according to the comorbidity of COPD: a COPD group (defined as forced expiratory volume in one second (FEV1.0) / forced vital capacity (FVC)&amp;lt;70% and FEV1.0&amp;lt;80% predicted [n=32]) or a non-COPD group [n=101]. Mild COPD patients (n=16) were excluded. Hemodynamics and respiratory parameters were compared. Results Hemodynamics improved similarly in both group (percent decrease of pulmonary vascular resistance; −61.1±12.3% in a COPD group, −65.8±11.1% in a non-COPD group, p=N.S). Patients in a COPD group showed improved respiratory function and oxygenation with FEV1.0% from 61.8±7.0% to 66.5±10.2% (p=0.02), and partial pressure of arterial oxygen from 60.9±10.6mmHg to 69.3±13.6mmHg (p&amp;lt;0.01). Higher vital capacity (r2=0.123, p=0.024), higher diffusing capacity for lung carbon monoxide (r2=0.308, p=0.028) at baseline were correlated with larger improvement of oxygenation after BPA in multivariate linear analyses. Lung injury per session was 1.6% in a COPD group. Conclusion The efficacy and safety of BPA for non-operable CTEPH with COPD were equivalent to those of patients without COPD. Oxygenation and FEV1.0% also improved in COPD patients. BPA might be considered even though patients comorbid COPD. Funding Acknowledgement Type of funding sources: None.

Relevance of comorbidities on initial combination therapy in pulmonary arterial hypertension.

Demographic characteristics of pulmonary arterial hypertension (PAH) patients have changed over time, but the effects of cardiovascular risk factors on risk status and pulmonary vascular resistance (PVR) reduction with initial oral combination therapy are not known. Therefore, we tested the relevance of cardiovascular comorbidities in this setting. The study enrolled 181 treatment-naive PAH patients with a 6-month (IQR 144-363 days) right heart catheterisation and risk assessment after initial oral combination therapy. Group A included 96 (53.0%) patients without cardiac comorbidities; Group B included 54 (29.8%) patients with one cardiac comorbidity; Group C included 31 (17.1%) patients with two cardiac comorbidities or more. Group C patients were older with a balanced sex distribution. There was a significant difference in PVR reduction moving from the absence to one or at least two cardiac comorbidities, respectively: median -45.0%, -30.3%, -24.3%. A European Respiratory Society/European Society of Cardiology low-risk status was present at first follow-up in 50 (52.0%) patients in Group A, 19 (35.1%) in Group B and 9 (29.0%) in Group C; a REVEAL 2.0 low-risk status was present at first follow-up in 41 (42.0%) patients in Group A, 15 (27.7%) in Group B and 7 (22.6%) in Group C. Group A patients were 2.3 times more likely to achieve/maintain a low-risk status compared with Group B and C (OR 2.27, 95% CI 1.15-4.54, p=0.02). No significant difference was observed between patients with non-cardiac comorbidities and those without comorbidities. Initial oral combination therapy seems associated with a less effective response for patients with cardiovascular comorbidities compared with the others, related to the magnitude of treatment-induced decrease in PVR.

A Rare Case of ALCAPA in Adult Asymptomatic Patient and Unusual Collateral Circulation: A Case Report

Anomalous Origin of the Left Coronary Artery from Pulmonary Artery (ALCAPA) syndrome is a rare congenital anomaly where the left main coronary artery arises from the pulmonary artery (PA) and the right coronary artery (RCA) originates normally from the aorta. The rapid decrease in pulmonary vascular resistance (PVR) soon after birth reverses the blood flow to the PA resulting in a left to right shunt and severe left ventricle (LV) ischemia. Left untreated, this congenital anomaly is associated with premature death. Rarely, some patients can survive to adult age due to development of collateral circulation usually from an ecstatic RCA. Most adult patients with ALCAPA die at mean age of 35 years. Very few cases were reported in the literature to survive until late 40s or 50s. We present the case of ALCAPA in an asymptomatic 54-year-old woman who found to have unusual collateral circulation justifying the absence of significant symptoms. Our patient underwent surgical correction with good results. We also review cases of ALCAPA that has been reported in the literature and we summarize treatment strategies. Learning objective: recognition of ALCAPA as one of coronary anomalies in adults even in asymptomatic individuals and recognition of the best diagnostic modality and the optimal management according to available literature.

Baseline Sex Differences in Pulmonary Arterial Hypertension Randomized Clinical Trials.

Rationale: Sex-based differences in pulmonary arterial hypertension (PAH) are known, but the contribution to disease measures is understudied. Objectives: We examined whether sex was associated with baseline 6-minute-walk distance (6MWD), hemodynamics, and functional class. Methods: We conducted a secondary analysis of participant-level data from randomized clinical trials of investigational PAH therapies conducted between 1998 and 2014 and provided by the U.S. Food and Drug Administration. Outcomes were modeled as a function of an interaction between sex and age or sex and body mass index (BMI), respectively, with generalized mixed modeling. Results: We included a total of 6,633 participants from 18 randomized clinical trials. A total of 5,197 (78%) were female, with a mean age of 49.1 years and a mean BMI of 27.0 kg/m2. Among 1,436 males, the mean age was 49.7 years, and the mean BMI was 26.4 kg/m2. The most common etiology of PAH was idiopathic. Females had shorter 6MWD. For every 1 kg/m2 increase in BMI for females, 6MWD decreased 2.3 (1.6-3.0) meters (P < 0.001), whereas 6MWD did not significantly change with BMI in males (0.31 m [-0.30 to 0.92]; P = 0.32). Females had lower right atrial pressure (RAP) and mean pulmonary artery pressure, and higher cardiac index than males (all P < 0.03). Age significantly modified the sex by RAP and mean pulmonary artery pressure relationships. For every 10-year increase in age, RAP was lower in males (0.5 mm Hg [0.3-0.7]; P < 0.001), but not in females (0.13 [-0.03 to 0.28]; P = 0.10). There was a significant decrease in pulmonary vascular resistance (PVR) with increasing age regardless of sex (P < 0.001). For every 1 kg/m2 increase in BMI, there was a 3% decrease in PVR for males (P < 0.001), compared with a 2% decrease in PVR in females (P < 0.001). Conclusions: Sexual dimorphism in subjects enrolled in clinical trials extends to 6MWD and hemodynamics; these relationships are modified by age and BMI. Sex, age, and body size should be considered in the evaluation and interpretation of surrogate outcomes in PAH.

Persistent Pulmonary Hypertension of the Newborn and Possible Premature Ductal Closure with History of In Utero Exposure to a Selective Serotonin Reuptake Inhibitor

Persistent pulmonary hypertension of the newborn more often affects term and near-term infants. It occurs when the anticipated postnatal decrease in pulmonary vascular resistance fails to occur. There is evidence in animal models of premature ductal closure and persistent pulmonary hypertension of the newborn in fetal mice with in-utero exposure to selective serotonin reuptake inhibitors, commonly prescribed antidepressants in pregnancy. This case raises suspicion about an association in a neonate between in-utero exposure to selective serotonin reuptake inhibitors and persistent pulmonary hypertension of the newborn secondary to premature ductal closure.

Beneficial Effects of Pulmonary Vasodilators on Pre-Capillary Pulmonary Hypertension in Patients with Chronic Kidney Disease on Hemodialysis.

Background: In patients with chronic kidney disease (CKD) on hemodialysis, comorbid pulmonary hypertension (PH) aggravates exercise tolerance and eventually worsens the prognosis. The treatment strategy for pre-capillary PH, including combined pre- and post-capillary PH (Cpc-PH), has not been established. Objectives: This study aimed to evaluate the impact of pulmonary vasodilators on exercise tolerance and pulmonary hemodynamics in patients with CKD on hemodialysis. Methods and Results: The medical records of 393 patients with suspected PH who underwent right heart catheterization were reviewed. Of these, seven patients had isolated pre-capillary PH and end-stage CKD on hemodialysis. Pulmonary vasodilators decreased pulmonary vascular resistance from 5.9 Wood units (interquartile range (IQR), 5.5–7.6) at baseline to 3.1 Wood units (IQR, 2.6–3.3) post-treatment (p = 0.02) as well as increased pulmonary capillary wedge pressure from 10 mmHg (IQR, 7–11) to 11 mmHg (IQR, 8–16) (p = 0.04). Pulmonary vasodilators increased the World Health Organization functional class I or II from 0% to 100% (p = 0.0002) and the 6 min walk distance from 273 m (IQR, 185–365) to 490 m (IQR, 470–550) (p = 0.03). Conclusions: Pulmonary vasodilators for PH in patients with CKD on hemodialysis decrease pulmonary vascular resistance and eventually improve exercise tolerance. Pulmonary vasodilators may help hemodialysis patients with pre-capillary PH, although careful management considering the risk of pulmonary edema is required.

Hemodynamic effects of balloon pulmonary angioplasty for the treatment of total and subtotal pulmonary artery occlusions in inoperable chronic thromboembolic pulmonary hypertension

BackgroundBalloon pulmonary angioplasty (BPA) has become a therapeutic option for inoperable chronic thromboembolic pulmonary hypertension (CTEPH). Despite significant improvement in the technique, treatment of subtotal (STO) and total (TO) pulmonary artery occlusions with BPA may pose risk, but the efficacy is less known. AimWe aimed to evaluate the safety and efficacy of BPA in STO/TO. MethodsWe included consecutive patients with inoperable CTEPH, who underwent BPA treatment. To evaluate the efficacy and safety we grouped all BPA sessions into these in which recanalization of at least one STO or TO was performed and into those without. The primary efficacy outcome was a decrease of pulmonary vascular resistance (PVR) after BPA sessions with STO/TO recanalization as compared to those without. ResultsWe analysed 169 BPA sessions in 50 CTEPH patients. Out of a total number of 831 lesions subjected for BPA, 169 were classified as STOs or TOs [123 (15,6%) and 39 (4,7%) respectively]. At least one STO/TO recanalization was successfully performed during 90 BPA sessions. Three (2,3%) STOs and 8 (20,5%) TOs were not recanalized despite repeated attempts. Recanalization of at least one STO/TO at the level of segmental pulmonary artery was associated with a significant PVR improvement as compared to subsegmental-only STO/TO recanalizations or no recanalizations (−126 ± 192 vs −38 ± 135 dyn·s·cm − 5, p = 0.007). The rate of complications was similar in STO/TO and non-STO/TO lesions (4.1% vs 2.4%, p = 0.22). ConclusionsThe use of BPA for the recanalization of subtotal and total PA occlusions is safe and feasible. Recanalization of segmental occlusive lesions leads to a significant improvement in PVR as compared to dilatation of nonocclusive ones.

Hemodynamic Implications of Sildenafil in Candidates for Heart Transplantation with Group 2 Pulmonary Hypertension: A Single Latin-American Center Registry

<h3>Purpose</h3> Heart failure is the most common cause of Group 2 pulmonary hypertension (PH). When it becomes fixed, it increases morbidity and mortality in heart transplantation (HTx). Reversing this situation is difficult, but the use of selective pulmonary vasodilators such as sildenafil could be a simple pharmacological tool in this setting. <h3>Objectives</h3> To analyze the prevalence of PH and the effect of Sildenafil in HTx candidates and its impact on mortality. <h3>Methods</h3> Patients who had undergone HTx over a ten-year period were analyzed retrospectively. PH was defined as mean pulmonary artery pressure (PAP) ≥25mmHg and/or pulmonary vascular resistance (PVR) > 3UW. Among the P with PH those who received sildenafil (Group A) and those who did not (Group B) were compared. Quantitative variables were compared with t-test or Mann-Whitney, and nominals with Fisher's test. Survival was analyzed using the log-rank test. A p<0.05 was considered significant <h3>Results</h3> From 01/2008 to 12/2018, 294 P undergone HTx, 30 P (10%) with combined transplantation, pediatric, re-transplantation, and without data, were excluded. Of the 217 P analyzed, 153 P (70%) presented PH, of whom 77P (51%) received sildenafil. Baseline characteristics are described in Table 1a. The causes for which 76 P (49%) with PH did not receive treatment with sildenafil were: intolerance to vasodilators, treatment with vasopressors, pulmonary congestion, and a tendency to reserve selective pulmonary vasodilators for those patients under previous treatment with ACEIs, ARAII or ARNI. Table 1b describes the hemodynamic variables for both groups. Table 1a shows a decrease in MPAP, transpulmonary gradient, and PVR without changes in cardiac index in Group A. There was no difference in mortality between both groups (graphic 1) <h3>Conclusion</h3> The use of Sildenafil in P with Group 2 PH could be an effective strategy to improve the hemodynamic profile during the candidacy for HTx, without impact on survival.

Accuracy of Estimated versus Calculated Mean Pulmonary Arterial Pressure

<h3>Purpose</h3> Less than half of heart failure physicians calculate mean pulmonary arterial pressures (mPAP). Rather, they are reported from approximation between the systolic and diastolic pulmonary pressures. Imprecise assessment of mPAP will result in inaccurate calculation of the pulmonary vascular resistance (PVR), which can alter perceived eligibility for heart transplantation (HT). We sought to assess for differences between reported and calculated mPAP and associated PVR. <h3>Methods</h3> We retrospectively analyzed consecutive patients undergoing right heart catheterization with milrinone drug study at our institution (2/2013-11/2019). Hemodynamics were measured at baseline and again after a 50 mcg/kg milrinone load. We retrospectively calculated the mPAP as (2/3)*(diastolic PA) + (1/3)*(systolic PA), as well as the corresponding PVR. We compared the median reported and calculated mPAPs at baseline and following milrinone study. Finally, we assessed the number of patients in which calculation of mPAP reclassified the PVR across the cut-off of 3.5 WU, which is often used to determine eligibility for HT. <h3>Results</h3> A total of 224 patients were included - median age 57 (IQR 48-66) years, 34% women, and 31% ischemic cardiomyopathy. At baseline, median mPAP remained the same when comparing the calculated (40 mmHg, IQR 31-47) versus the reported mPAP (40 mmHg, IQR 32-48), though calculation resulted in significantly less variation in measurements (<i>p<</i>0.001). Calculated PVR, 3.5 WU (IQR 2.3-4.6), was significantly lower than reported PVR, 3.8 WU (IQR 2.5-5.1), <i>p<</i> 0.001. After milrinone study, final calculated mPAP, 33 mmHg (IQR 26-41), again had significantly less variability compared to reported, 33 mmHg (IQR 25-42), <i>p</i><0.001, and subsequent PVR was significantly lower with calculated mPAP, PVR 2.65 WU (IQR 1.88-3.70), compared to reported mPAP, PVR 2.78 WU (IQR 1.93-3.78), <i>p</i><0.001. There were 46 patients (21%) in which the PVR transitioned across the PVR cutoff of 3.5 WU after calculation of mPAP - 40 (18%) had PVR decrease to ≤ 3.5 from > 3.5, and 6 (3%) had PVR increase to > 3.5 from ≤ 3.5. <h3>Conclusion</h3> Calculation of mPAP resulted in less variation in measurement, affecting downstream calculation of PVR. More than one in five patients had PVR values transition across the cut-off of 3.5 WU following calculation of mPAP, which could alter subsequent eligibility for HT.

Hidden systolic dysfunction of the right ventricle in patients with increased pulmonary vascular resistance 3 months after COVID-19 pneumonia

Funding AcknowledgementsType of funding sources: None.BackgroundCoronavirus disease 2019 (COVID-19) is caused by the novel severe acute respiratory syndrome coronavirus 2. Pulmonary vascular resistance (PVR) is an important hemodynamic variable used in the management of patients with cardiovascular and pulmonary pathology. Doppler echocardiography has significantly impacted clinical medicine by its ability to assess intracardiac hemodynamics noninvasively. It seems actual to reveal the relationship between right heart function and lungs involvement in COVID-19.PurposeTo assess the relationship right ventricular (RV) echocardiographic structural and functional parameters with indicators of increased pulmonary vascular resistance (PVR) in patients 3 months after COVID-19 pneumonia.Methods96 patients (mean age 47.6 ± 15.2 years) were examined during hospitalization and at control visit (3 months follow-up). The equation tricuspid regurgitation velocity / time-velocity integral of the RV outflow tract X 10 + 0.16 has been used to determine PVR. Patients were divided into 2 groups: I group (n = 31) – patients with increase of PVR ≥1.5 Wood unit (WU) and II group (n = 65) – with decrease of PVR <1.5 WU.ResultsAt baseline groups did not differ in main clinical characteristics, including severity of lung involvement in COVID-19 by computed tomography (32.7 ± 22.1% vs 36.5 ± 20.4%, р=0.418). Linear, planimetric and volumetric parameters did not differ significantly between groups. At the control visit RV free wall (FW) global endocardial longitudinal strain (LS) (-19.3 [-17.9; -25.8] % in group I vs -23.4 [-19.8; -27.8] % in group II, p = 0.048), tricuspid annular plane systolic excursion (21.7 ± 3.8 mm vs 23.3 ± 3.4 mm, p = 0.040) and RV maximum systolic velocity assessed by tissue Doppler imaging (12.3 ± 2.4 cm/s vs 13.4 ± 2.0 cm/s, p = 0.024) were significantly reduced in group I, systolic pulmonary artery pressure (sPAP) according to Otto C. (32.0 [26,0; 35.0] mm Hg vs 23.0 [20.0; 28.0] mm Hg, p <0.001) was significantly increased in group I. According to logistic regression only endocardial RV FW LS (OR 0.859; 95% CI 0.746 - 0.989; p = 0.034) and sPAP (OR 1.248; 95% CI 1.108 - 1405; p <0.001) had an independent relationship with increase of PVR. According to Spearman correlation analysis the moderate relationship was found between PVR and mean pulmonary artery pressure according to Mahan G. (r = 0.516, p = 0.003), PVR and RV–pulmonary artery coupling (r=-0.509, p = 0.007) in group I at the control visit.ConclusionHidden RV systolic dysfunction defined as decreased endocardial RV FW LS to -19.3% is associated with increased PVR ≥1.5 WU in patients 3 months after COVID-19 pneumonia. Figure. RV FW LS by STE