Baseline Mean Pulmonary Artery Pressure Research Articles

Impact of different sequential triple oral combination therapies based selexipag on outcomes in pulmonary arterial hypertension.

While the GRIPHON study and others have confirmed the efficacy and safety of selexipag with single, dual, and initial triple combination therapy for patients with pulmonary arterial hypertension (PAH), multicenters studies concerning diverse triple oral combination therapies based on selexipag are limited. This study was conducted to evaluate the effects of various sequential triple oral combination therapies on PAH outcomes. A retrospective study was carried out involving 192 patients from 10 centers, who were receiving sequential triple oral combination therapy consisting of an endothelin receptor antagonist (ERA), a phosphodiesterase 5 inhibitor (PDE5i)/riociguat and selexipag. Clinical parameters, event-free survival, and all-cause survival were assessed and analyzed at baseline and posttreatment. Among the 192 patients, 37 were treated with ERA + riociguat + selexipag, and 155 patients received ERA + PDE5i + selexipag. Both sequential triple oral combination therapies improved the World Health Organization functional class and raised the count of low-risk parameters. As a result of the larger patients' population in the ERA + PDE5i + selexipag group, these individuals exhibited significant increases in 6-minutewalking distance(6MWD), pulmonary arterial systolic pressure,pulmonary arterial pressure, right ventricle, andeccentricity index, and significant decreases in N-terminal probrain natriuretic peptide after 6 months of treatment. Nevertheless, both sequential triple oral combination therapy groups demonstrated similar shifts in these clinical parameters between baseline and 6 months. Baseline 6MWD and mean pulmonary arterial pressure were independent predictors of survival in patients undergoing ERA + PDE5i + selexipag therapy. Importantly, no significant differences were found in 6-month event-free survival and all-cause survival between two groups. Different oral sequential triple combination therapies based on selexipag could comparably improve outcomes in patients with PAH.

Sonographic assessment of mean pulmonary artery pressure and diaphragmatic excursion in chronic respiratory failure patient after using home non-invasive positive pressure ventilation

BackgroundNon-invasive positive pressure ventilation (NIPPV) has emerged as a recognized and effective long-term therapeutic approach for individuals suffering from chronic respiratory insufficiency resulting from various diverse disorders. Nevertheless, providing home non-invasive positive pressure ventilation encounters several challenges, including compliance, training inadequacies, and limited resources. Therefore, the objective of this study was to observe the impact of home non-invasive positive pressure ventilation on patients with chronic respiratory failure, specifically focusing on its effects on the mean pulmonary artery pressure, diaphragmatic excursion, and associated complications.ResultsThe study included a total of 48 patients, consisting of 26 males (54.1%) and 22 females (45.9%). The baseline mean pulmonary artery pressure (PAP) was found to be 39.79 ± 7.51. Additionally, the baseline diaphragmatic excursion in quiet breathing was measured to be 1.80 ± 0.38 cm, while the baseline diaphragmatic excursion in deep breathing was recorded as 4.35 ± 0.99 cm. Following the implementation of home non-invasive ventilation, specifically bilevel-positive airway pressure or continuous positive airway pressure, significant improvements were observed in the aforementioned parameters. The most commonly reported complications among the patients included skin ulcers and aerophagia. Furthermore, mortality rate of 6.3% was observed.ConclusionsThe use of home non-invasive positive pressure ventilation has been shown to be a successful and sustainable therapeutic approach for persons suffering from chronic respiratory failure. This therapy method has significantly improved PAP, diaphragm force, and overall mortality rates. The use of ultrasonography to evaluate pulmonary pressure or diaphragmatic excursion is considered a beneficial and straightforward approach for the follow-up of subjects with chronic respiratory failure.

Sacubitril/valsartan affects pulmonary arterial pressure in heart failure with preserved ejection fraction and pulmonary hypertension.

AimsPrior studies have not fully characterized the haemodynamic effects of the angiotensin receptor‐neprilysin inhibitor (ARNI) sacubitril/valsartan in heart failure with preserved ejection fraction and pulmonary hypertension (HFpEF–PH). The aim of the Treatment of PH With Angiotensin II Receptor Blocker and Neprilysin Inhibitor in HFpEF Patients With CardioMEMS Device (ARNIMEMS‐HFpEF) study is to assess pulmonary artery pressure (PAP) dynamics by means of implanted PAP monitors in patients with HFpEF–PH treated with sacubitril/valsartan.Methods and resultsThis single‐arm, investigator‐initiated, interventional study included 14 consecutive ambulatory symptomatic HFpEF–PH patients who underwent CardioMEMS implantation prior to enrolment [mean ejection fraction 60.4 ± 7.2%, baseline mean PAP (mPAP) 33.9 ± 7.6 mmHg]. Daily PAP values were examined during three periods: a 6 week period after CardioMEMS implantation and before sacubitril/valsartan treatment (pre‐ARNI), a 6 week period with sacubitril/valsartan treatment (ARNI ON), and a 6 week period of sacubitril/valsartan withdrawal (ARNI OFF). The primary endpoint was change in mPAP with and without sacubitril/valsartan. Secondary endpoints included changes in 6 min walking distance, B‐line sum in lung ultrasound, and quality of life (QoL). During the study period, 1717 mPAP measurements were recorded. Between pre‐ARNI vs. ARNI ON, mPAP significantly declined by −4.99 mmHg [95% confidence interval (CI) −5.55 to −4.43]. Between ARNI ON vs. ARNI OFF, mPAP significantly increased by +2.84 mmHg [95% CI +2.26 to +3.42]. Between pre‐ARNI vs. ARNI ON, we found an improvement in 6 min walking distance, B‐lines, and QoL. Mean loop diuretic management did not differ between periods.ConclusionsSacubitril/valsartan significantly reduced mPAP in patients with HFpEF–PH, independent of loop diuretic management, together with improvement in functional capacity, lung congestion, and QoL. Sacubitril/valsartan may be a therapeutic alternative in HFpEF–PH.

Efficacy of interatrial shunt devices: an opening window to acute pulmonary hypertensive crisis and chronic pulmonary arterial hypertension.

The current study aimed to elucidate the efficacy of interatrial shunt device (IASD) for the treatment of acute pulmonary hypertensive crisis (PHC) and chronic pulmonary arterial hypertension (PAH). After establishing chronic PAH models using dehydrogenized monocrotaline (DHMCT), PAH dogs were implanted with IASDs (group A) or received no intervention (group B). One month later, DHMCT was injected again to establish an acute PHC. The prognosis, hemodynamics, ultrasound cardiography, electrocardiogram, and lung pathology of the dogs were observed. The baseline mean pulmonary arterial pressure increased from 12.70 ± 1.03 to 19.95 ± 1.75mmHg and established a chronic PAH model 2 months after DHMCT injection (1.50mg/kg). After an additional injection of DHMCT (1.50mg/kg) in the chronic PAH model, acute PHC occurred. Mean PAP, sPAP, and pulmonary vascular resistance increased to 22.67 ± 1.80mmHg, 35.70 ± 1.66mmHg, and 12.50 ± 3.50 WOOD U, respectively. Cardiac output (CO) decreased to 1.31 ± 0.26 L/min, and the right-to-left shunt caused hypoxemia. The survival rates of the dogs with and those without IASD were 70.0% and 22.2% (P = 0.037), respectively. Six months after PHC, the CO between the dogs with and those without IASD were 1.44 ± 0.11 L/min and 1.18 ± 0.04 L/min (P = 0.028). The long-term survival rates were 50.0% and 22.2%, respectively (P = 0.21). IASD might be efficacious and beneficial for treating acute PHC and chronic PAH, as well as improving prognosis.

Oxygen inhalation can selectively dilate pulmonary arteries in patients with chronic thromboembolic pulmonary hypertension before balloon angioplasty

BackgroundPulmonary injury is a major complication of balloon pulmonary angioplasty (BPA) for chronic thromboembolic pulmonary hypertension (CTEPH). Lung injury after BPA can be exacerbated by a high mean pulmonary arterial pressure (PAP). Although oxygen inhalation is expected to lower mean PAP in patients with CTEPH, no relevant investigation has been conducted. MethodsConsecutive patients with CTEPH who underwent BPA were enrolled in this study. We evaluated the hemodynamics using right heart catheterization while breathing ambient air and with administration of 5 L/min oxygen for 10 min. ResultsThis study included 52 consecutive patients with CTEPH, of whom 23 (44%) were treated with specific pulmonary vasodilators. Exposure to oxygen was well tolerated. Oxygen administration significantly decreased mean PAP by 3.8 ± 3.2 mmHg (p<0.001) and pulmonary vascular resistance by 0.8 ± 1.8 Wood units (p<0.001). Moreover, the ratio of pulmonary vascular resistance to systemic vascular resistance was significantly reduced by 13.5% (p<0.001). Multivariate regression analysis identified baseline mean PAP (β = -0.427, p = 0.006) as the only significant predictor of decreased mean PAP under oxygen administration. No significant difference in oxygen effect on mean PAP was found between patients with and without vasodilators. ConclusionsIn patients with CTEPH, 5 L/min supplemental oxygen inhalation could decrease mean PAP significantly by selective pulmonary artery dilatation, regardless of the usage of vasodilators, and thus could be helpful to maximize the safety of BPA. Clinical trial registrationUMIN Clinical Trials Registry (No.: UMIN000026882); URL: https://www.umin.ac.jp/ctr/index.htm.

Levosimendan, milrinone, and dobutamine in experimental acute pulmonary embolism.

Acute pulmonary embolism is a frequent condition in emergency medicine and potentially fatal. Cause of death is right ventricular failure due to increased right ventricular afterload from both pulmonary vascular obstruction and vasoconstriction. Inodilators are interesting drugs of choice as they may improve right ventricular function and lower its afterload. We aimed to investigate the cardiovascular effects of three clinically relevant inodilators: levosimendan, milrinone, and dobutamine in acute pulmonary embolism. We conducted a randomized, blinded, animal study using 18 female pigs. Animals received large autologous pulmonary embolism until doubling of baseline mean pulmonary arterial pressure and were randomized to increasing doses of each inodilator. Effects were evaluated with bi-ventricular pressure–volume loop recordings, right heart catheterization, and blood gas analyses. Induction of pulmonary embolism increased right ventricular afterload and pulmonary pressure (p < 0.05) causing right ventricular dysfunction. Levosimendan and milrinone showed beneficial hemodynamic profiles by lowering right ventricular pressures and volume (p < 0.001) and improved right ventricular function and cardiac output (p < 0.05) without increasing right ventricular mechanical work. Dobutamine increased right ventricular pressure and function (p < 0.01) but at a cost of increased mechanical work at the highest doses, showing an adverse hemodynamic profile. In a porcine model of acute pulmonary embolism, levosimendan and milrinone reduced right ventricular afterload and improved right ventricular function, whereas dobutamine at higher doses increased right ventricular afterload and right ventricular mechanical work. The study motivates clinical testing of inodilators in patients with acute pulmonary embolism and right ventricular dysfunction.

Levosimendan, milrinone and dobutamine in acute experimental pulmonary embolism

Abstract Funding Acknowledgements Type of funding sources: Foundation. Main funding source(s): Laerdal Foundation for Acute Medicine, Novo Nordisk Foundation Background/Introduction: Acute pulmonary embolism (PE) is a frequent condition in acute cardiac care and is potentially fatal. Cause of death is right ventricular (RV) failure due to increased RV afterload from both pulmonary vascular obstruction and vasoconstriction. Inodilators are interesting drugs of choice as they may improve RV function and lower its afterload. Purpose We aimed to investigate the cardiovascular effects of three clinically relevant inodilators: levosimendan, milrinone and dobutamine in acute PE. Methods We conducted a randomized, blinded, animal study using 18 female pigs. Animals received large autologous PE until doubling of baseline mean pulmonary arterial pressure and were randomized to four logarithmically increasing doses of each inodilator. Effects were evaluated with bi-ventricular pressure-volume loop recordings, right heart catheterization and blood gas analyses. Results Induction of PE increased RV afterload and pulmonary pressure (p &amp;lt; 0.05) causing RV dysfunction. Levosimendan and milrinone showed beneficial hemodynamic profiles by lowering RV pressures and volume (p &amp;lt; 0.001) and improved RV function and cardiac output (p &amp;lt; 0.05) without increasing RV mechanical work. Dobutamine increased RV pressure and function (p &amp;lt; 0.01) but at a cost of increased mechanical work at the highest doses, showing an adverse hemodynamic profile. See Figure. Conclusion(s): In a porcine model of acute PE, levosimendan and milrinone reduced RV afterload and improved RV function, whereas dobutamine at higher doses increased RV afterload and RV mechanical work. The study motivates clinical testing of inodilators in patients with acute PE and RV dysfunction. Abstract Figure. Inodilators in acute pulmonary embolism

Oxygen Therapy Lowers Right Ventricular Afterload in Experimental Acute Pulmonary Embolism.

To investigate if oxygen could unload the right ventricle and improve right ventricle function in a porcine model mimicking intermediate-high risk acute pulmonary embolism. Controlled, blinded, animal study. Tertiary university hospital, animal research laboratory. Female, Danish pigs (n = 16, approximately 60 kg). Acute autologous pulmonary embolism was induced until doubling of baseline mean pulmonary arterial pressure. Group 1 animals (n = 8) received increasing Fio2 (40%, 60%, and 100%) for time intervals of 15 minutes returning to atmospheric air between each level of Fio2. In group 2 (n = 8), the effects of Fio2 40% maintained over 75 minutes were studied. In both groups, pulmonary vasodilatation from inhaled nitric oxide (40 parts per million) was used as a positive control. Effects were evaluated by biventricular pressure-volume loop recordings, right heart catheterization, and arterial and mixed venous blood gasses. Pulmonary embolism increased mean pulmonary arterial pressure from 15 ± 4 to 33 ± 6 mm Hg (p = 0.0002) and caused right ventricle dysfunction (p < 0.05) with troponin release (p < 0.0001). In group 1, increasing Fio2 lowered mean pulmonary arterial pressure (p < 0.0001) and pulmonary vascular resistance (p = 0.0056) and decreased right ventricle volumes (p = 0.0018) and right ventricle mechanical work (p = 0.034). Oxygenation was improved and pulmonary shunt was lowered (p < 0.0001). Maximal hemodynamic effects were seen at Fio2 40% with no additional benefit from higher fractions of oxygen. In group 2, the effects of Fio2 40% were persistent over 75 minutes. Supplemental oxygen showed the same pulmonary vasodilator efficacy as inhaled nitric oxide (40 parts per million). No adverse effects were observed. In a porcine model mimicking intermediate-high risk pulmonary embolism, oxygen therapy reduced right ventricle afterload and lowered right ventricle mechanical work. The effects were immediately present and persistent and were similar to inhaled nitric oxide. The intervention is easy and safe. The study motivates extended clinical evaluation of supplemental oxygen in acute pulmonary embolism.

Continual Improvement in Pressure Gradient at the Lesion After Balloon Pulmonary Angioplasty for Chronic Thromboembolic Pulmonary Hypertension

BackgroundLung injury is a serious complication of balloon pulmonary angioplasty (BPA) for chronic thromboembolic pulmonary hypertension (CTEPH). Selecting a smaller balloon might minimize the occurrence of lung injury; however, it could also increase the risk of restenosis. MethodsWe analyzed the first target lesions in the initial BPA procedure in 34 consecutive patients with CTEPH. We measured proximal pressure with a guiding catheter and distal pressure with a pressure wire. We retrospectively investigated pressure gradients at the lesions before and immediately after the initial dilation with a smaller balloon and before the second procedure. ResultsThe proximal pressure decreased, and the distal pressure increased immediately after the initial balloon dilation. The pressure gradient at the lesion diminished significantly by the second procedure (from 26.4 ± 10.7 to 18.2 ± 9.9 mm Hg, P < 0.001) without serious complications. The residual pressure gradient had further diminished (to 9.8 ± 6.5 mm Hg, P = 0.02) until the second procedure. The reduction in pressure gradient at the lesion from immediately after the initial balloon dilation to the second procedure was positively correlated with both the baseline mean pulmonary arterial pressure (r2 = 0.23, P = 0.004) and residual pressure gradient immediately after the initial balloon dilation (r2 = 0.58, P < 0.001). ConclusionsThe residual pressure gradient at the lesion diminished continually after dilation with a smaller balloon. This strategy could decrease pulmonary arterial pressure safely. It would be reasonable to dilate the lesions sequentially in 2 procedures.

Abstract 13875: Pulmonary Artery Pressure Guided Heart Failure Management Reduces Hospitalizations Across All Stages of Chronic Kidney Disease

Introduction: Pulmonary artery pressure (PAP)-guided treatment reduces heart failure hospitalizations (HFH) in randomized and “real world” studies. Underlying CKD in HF patients portends poorer outcomes. This analysis was performed to determine if benefit of PAP-guided HF therapy persists with increasing CKD severity. Methods: This retrospective cohort study was conducted in NYHA Class III HF recipients of the PAP sensor enrolled in the CardioMEMS Post Approval Study. Patients were subdivided into quartiles of glomerular filtration rates estimated by MDRD equation (eGFR). Rates of HFH 1 year before versus 1 year after PAP sensor implantation were compared across quartiles of eGFR using the Andersen-Gill Cox proportional hazards model, while accounting for competing risk of death, advanced HF therapies, and progression to end-stage kidney disease. Multivariate analysis was performed to identify independent predictors of CKD (baseline eGFR &lt; 90 mL/min/1,73m 2 ) progression. Results: Among 1200 PAP sensor recipients, 1119 had concomitant CKD with CKD stages 3 and 4 occurring in 754 patients (67.4%). In CKD patients, 40.6%, 42.1%, and 17.3%, respectively, demonstrated worse, unchanged, or improved CKD stage. Compared to 12 pre-implant months, HFH rates dropped in 12 months after implant across all eGFR quartiles (Table). PA systolic, diastolic, and mean pressures decreased from baseline to 24 months in all GFR quartiles. The baseline mean PAP as a continuous variable independently predicted CKD progression (OR: 1.027, p= 0.0006). Conclusion: Reduction of HFH by PAP-guided therapy occurred across CKD stages in a large HF population receiving the CardioMEMS sensor after Food and Drug Administration approval. Thus, PAP monitoring enables safe HF therapy optimization even in patients with advanced CKD. Since higher baseline mean PAP independently forecasts CKD worsening, HF patients with this unfavorable hemodynamic value require intensified monitoring.

Usefulness of peripheral-pressure-directed balloon pulmonary angioplasty for chronic thromboembolic pulmonary hypertension

Abstract Background Balloon pulmonary angioplasty (BPA) in expert center may be considered in patients with chronic thromboembolic pulmonary hypertension (CTEPH) who are technically non-operable for pulmonary endarterectomy. BPA based on objective quantitative methods has not been established. The endpoint at BPA sessions has not been clarified yet. Objectives The purpose of this study was to investigate the usefulness of BPA according to peripheral pressure measured by pressure wire or catheter. Methods This study included consecutive 143 CTEPH who underwent cardiopulmonary exercise test with right heart catheterization after BPA. All patients were divided into 2 groups such as angio-guided (n=47) group or pressure-guidedgroup (n=96). In pressure-guided group, the pulmonary arterial pressure (PAP) proximal and distal to the target lesion and the ratio of the 2 pressures were measured by the pressure wire or catheter. the endpoint was determined to when the pressure ratio of distal to proximal pressures was &amp;gt;0.7 to 0.8 finally. The dilation was stopped when the distal mean PAP after each dilation reached 35 mm Hg and when the baseline mean PAP was &amp;gt;35 mm Hg. Changes of hemodynamic parameters such as PAP and pulmonary vascular resistance (PVR) from baseline, and mean PAP and PVR at peak oxygen consumption, and pulmonary arterial pressure – cardiac output (PA-CO) slope were compared between two groups. All data except changes of hemodynamics from baseline were expressed by median [25th percentile-75th percentile]. Changes of hemodynamics from baseline were expressed by average [95% confidence interval] Results The median age and male were 66 [56–72] years old and 35. There were no significant differences in number of sessions and dilated vessels between two groups (Angio-guided group vs. Pressure-guided group: 4 [3–6] vs. 4 [3–5], P&amp;gt;0.05; 19 [12–22] vs. 17 [13–22], P&amp;gt;0.05). Changes of PAP and PVR from baseline in pressure-guided group was significantly higher than in angio-guided groups (Angio-guided group vs. Pressure-guided group; ΔPAP: −19 [−20 to −17] vs. −20 [−21 to −20], P&amp;gt;0.05; ΔPVR: −6.0 [−6.3 to −5.7] vs. −6.6 [−6.8 to −6.3], P&amp;lt;0.01). Mean PAP and PVR at peak oxygen consumption (VO2) and PA-CO slope in pressure-guided group were significantly lower than in angio-guided group (Angio-guided group vs. Pressure-guided group; PAP at VO2: 43 [36–50] vs. 39 [34–43], P&amp;lt;0.05; PVR at VO2: 2.7 [1.9–4.5] vs. 2.2 [1.6–2.9], P&amp;lt;0.01; PA-CO slope: 3.8 [2.1–5.2] vs. 2.9 [1.9–4.0], P&amp;lt;0.05). Conclusions Peripheral-pressure-directed BPA can improve hemodynamics at rest and exercise more effectively. Funding Acknowledgement Type of funding source: None

Pulmonary hypertension and pregnancy. Is it time to reconsider recommendations in certain groups? Contemporary outcomes in a tertiary referral centre

Abstract Background and aims Pregnancy is as a major risk scenario for pulmonary hypertension (PH) females. Disease targeted therapy (DTT) has dramatically changed prognosis in certain PH groups, namely: pulmonary arterial hypertension (PAH), chronic thromboembolic PH (CTEPH) or segmental-PH; also facilitating pregnancy management. In spite a more benign course in the responders to calcium channel blockers subgroup (R-CCB), maternal mortality is thought to remain high and current recommendations still consider all PH-patients as very high risk (mWHO IV). We aimed to analyse pregnancy outcomes in PAH, CTEPH and segmental-PH in a contemporary cohort and to specifically assess pregnancy risks in the R-CCB subgroup. Methods and results All pregnant PAH, CTEPH and segmental PH patients and patients transferred within 8 weeks post-delivery between January 2000 and January 2020 to our centre were studied. 28 pregnancies were included. Mean age 28±6 years. Underlying aetiology: 10 (36%) Idiopathic-PAH, 4 (14%) Heritable-PAH (1 of them veno-occlussive disease-POVD-), 2 (7.1%)PAH-connective tissue disease, 9 (32,1%) PAH-congenital heart disease (1 Eisenmenger), 1 (3.6%) CPETH, 2 (7.1%) segmental-HP. 21% were R-CCB. From the overall 28 pregnancies, 32% underwent early termination of pregnancy (ETP). When pregnancy was continued in non-responders, 5 (23%) were admitted from cardiac causes and up to 13% required inotropes. 66.7% of non-responders patients needed uptitration of PH-DTT along pregnancy (19% being discharged on prostacyclins). Considering the whole cohort, two patients (7.1%) died along the pregnancy period, both non-responders PAH (1 IPAH and 1 POVD). One died at ETP and the other one 48 hours after C-section at week 22. No R-CCB presented with maternal complications, and all continued on CCB without needing any change on treatment. Regarding the new-born, average gestational age was 28 weeks and 53% suffered from some neonatal morbidity (only 1 R-CCB), including 1 neonatal death. From a haemodynamic perspective, baseline mean pulmonary artery pressure (mPAP) was 41.9±15 mmHg, pulmonary vascular resistances (PVR) were at 7.1±4 WU. If haemodynamics were also available after pregnancy (53%), no significant increase in PVR was noted, although the required DTT was remarkably higher. Survival-free of death or lung transplantation (Figure 1) was calculated at 78.57% over a median long-term follow-up of 6 years. Conclusions DTT has improved outcomes in pregnant PH females. Although mortality related to pregnancy appears high but not prohibited, maternal and neonatal morbidity is still very high. Moreover, ETP in this population is not without complications. In addition, DTT often requires uptitration suggesting disease progression. Nevertheless, R-CCB females appear to be able to complete pregnancy without events supporting our suggestion to reconsider their estimated pregnancy-associated risks. Figure 1. 5-year survival Funding Acknowledgement Type of funding source: None

Association between Arrhythmia and Pulmonary Artery Pressure in Heart Failure Patients Implanted with a Cardiac Defibrillator and Ambulatory Pulmonary Artery Pressure Sensor.

The association between ventricular arrhythmia (VA) burden or defibrillator therapy and pulmonary artery pressure (PAP) has not been characterized in an ambulatory setting; thus, we sought in the present research to determine the relationship between ambulatory PAP and VA burden. A retrospective cohort study involving patients with an implantable cardiac defibrillator and CardioMEMS™ PAP sensor (Abbott Laboratories, Chicago, IL, USA) both transmitting remotely into the Merlin.net™ patient care network (Abbott Laboratories, Chicago, IL, USA) was conducted. VA and therapy burden in the six months following sensor implant were stratified by the baseline mean PAP. Patients with PAPs of 25 mmHg to 35 mmHg and those with PAPs of 35 mmHg or more were compared with individuals with PAPs of less than 25 mmHg. The change in VA burden was reported using the averaged mean PAP reduction during the first three months. A total of 162 patients aged 69.4 years ± 10.9 years were included (74% male) with a baseline mean PAP of 36.2 mmHg ± 10.4 mmHg. Twenty patients with a baseline mean PAP of less than 25 mmHg had no VAs over six months. For 61 patients with a baseline mean PAP of between 25 mmHg and 35 mmHg, the annualized number of days with ventricular tachycardia (VT)/ventricular fibrillation (VF) was 1.65/patient-year (p < 0.001), with 8% of patients having VT/VF events. For 81 patients with a baseline mean PAP of 35 mmHg or more, 19% of patients had a VT/VF event and an annualized number of days with VT/VF events of 1.45/patient-year (p < 0.001). When analyzing the treatment effect, a reduction of 3 mmHg or more in mean PAP over three months reduced arrhythmia burden over the next three months as compared with in patients without such an improvement. In conclusion, it is indicated that VAs are associated with high PAPs, and a reduction in PAP may lead to a reduction in VAs in real-world ambulatory patients.

Predictors of Hemodynamic Response to Intra-Aortic Balloon Pump Therapy in Patients with Acute Decompensated Heart Failure and Cardiogenic Shock

Introduction There is renewed interest in the utility of the intra-aortic balloon pump (IABP) for short-term and durable support in patients with chronic systolic heart failure (HF) who present with acute decompensation and cardiogenic shock (CS). However, the clinical characteristics of IABP-responders and non-responders remain incompletely defined. We sought to identify predictors of early IABP response to guide optimal use of IABP therapy in this population. Methods We retrospectively analyzed the records of chronic systolic HF patients who presented at our institution between 2011-2018 with acute decompensated HF with hemodynamic evidence of CS and underwent IABP placement. IABP-responder was defined as having an immediate increase in cardiac output (CO) and an immediate decrease in mean pulmonary artery pressure (MPAP) above the median values of the cohort. Logistic regression was used to identify predictors of hemodynamic response. Results During the study period, 218 chronic systolic HF patients underwent IABP insertion for acute decompensation with CS. The mean age was 59.4 ±13.4 years, 79.8% were men, and 38.5% had ischemic cardiomyopathy (ICM). The average hemodynamic response to IABP in the whole cohort was a CO increase of 0.57 ±0.85L/min and a MPAP reduction of 5.1 ±7.6mmHg; IABP-responders had a CO increase of 1.21 ±0.87L/min and a MPAP reduction of 12.1 ±5.9mmHg (figure). Univariable predictors of IABP-response were ICM, presence of severe mitral regurgitation, baseline heart rate, elevated MPAP, and elevated systemic vascular resistance (SVR). Following multivariable logistic regression, independent predictors of IABP-response were elevated baseline SVR (OR 2.05, 95% CI 1.01 - 4.17; p=0.047) and elevated MPAP (OR 2.47, 95% CI 1.23 - 5.00; p=0.01). MPAP reduction decreased the odds of death or need for escalation to another short-term circulatory support device while CO increase did not [OR 0.52 (0.28 - 0.97; p=0.04) vs. 0.83 (0.45 - 1.54; p=0.56)]. Conclusions A subset of chronic systolic HF patients had a robust hemodynamic response to IABP insertion with CO augmentation and MPAP reduction. Elevated baseline SVR and MPAP are predictors of robust response following device insertion. These parameters may be used to identify patients who may respond favorably to IABP counterpulsation therapy.

French experience of balloon pulmonary angioplasty for chronic thromboembolic pulmonary hypertension.

AimsTo evaluate safety and efficacy of balloon pulmonary angioplasty (BPA) in a large cohort of patients with chronic thromboembolic pulmonary hypertension (CTEPH).MethodsFrom 2014 to 2017, 184 inoperable CTEPH patients underwent 1006 BPA sessions. Safety and efficacy during the first 21 months (initial period) were compared with those of the last 21 months (recent period). A total of 154 patients had a full evaluation after a median duration of 6.1 months.ResultsOverall, there was a significant improvement in New York Heart Association functional class, 6-min walk distance (mean change +45 m), and a significant decrease in mean pulmonary artery pressure (PAP) and in pulmonary vascular resistance (PVR) by 26% and 43%, respectively. The percentage decreases of mean PAP and PVR were 22% and 37% in the initial period versus 30% and 49% in the recent period, respectively (p<0.05). The main complications included lung injury, which occurred in 9.1% of 1006 sessions (13.3% in the initial period versus 5.9% in the recent period; p<0.001). Per-patient multivariate analysis revealed that baseline mean PAP and the period during which BPA procedure was performed (recent versus initial period) were the strongest factors related to the occurrence of lung injury. 3-year survival was 95.1%.ConclusionThis study confirms that a refined BPA strategy improves short-term symptoms, exercise capacity and haemodynamics in inoperable CTEPH patients with an acceptable risk–benefit ratio. Safety and efficacy improve over time, underscoring the unavoidable learning curve for this procedure.

N-terminal pro–B-type natriuretic peptide for monitoring after balloon pulmonary angioplasty for chronic thromboembolic pulmonary hypertension

Balloon pulmonary angioplasty (BPA) is an emerging interventional treatment option for chronic thromboembolic pulmonary hypertension (CTEPH). The non-invasive monitoring of CTEPH patients is a clinical challenge. In this study we examined changes in N-terminal pro-B-type natriuretic peptide (NT-proBNP) in patients undergoing BPA for inoperable CTEPH and related them to peri-procedural success. In this study we analyzed a total of 51 consecutive patients who underwent BPA treatment and completed a 6-month follow-up (6-MFU) between March 2014 and March 2017. Serum samples for NT-proBNP measurement were collected before every BPA and at 6-MFU. The 51 patients underwent 265 interventions involving angioplasty of a total of 410 vessels. The 6-month survival rate was 96.1%. The baseline (BL) mean pulmonary artery pressure (PAP) was 39.5 ± 12.1 mm Hg, pulmonary vascular resistance (PVR) was 515.8 ± 219.2 dynes/s/cm5 and the median NT-proBNP level was 820 (153 to 1,871.5) ng/liter. At BL, World Health Organization functional class (FC) was ≥III in 96.1% of the patients, whereas, at 6-MFU, 11.8% were in WHO FC ≥III. At 6-MFU, mean PAP (32.6 ± 12.6 mm Hg; p < 0.001), PVR (396.9 ± 182.6 dynes/s/cm5; p < 0.001) and NT-proBNP (159.3 [84.4 to 464.3] ng/liter; p < 0.001) levels were reduced. The decrease in NT-proBNP levels correlated with the decrease in mean PAP (rrs = 0.43, p = 0.002) and PVR (rrs = 0.50, p = 0.001). A reduction in the NT-proBNP level of 46% indicated a decrease in mean PAP of ≥25% (area under the curve [AUC] = 0.71) and a reduction of 61% indicated a decrease in PVR of ≥35% (AUC 0.77). Our results demonstrate that NT-proBNP levels decrease after BPA, providing valuable evidence of procedural success. NT-proBNP measurement allows identification of patients who are BPA non-responders and may thus be a valuable adjunct in therapy monitoring.

Abstract 24015: Genome-Wide Association Study of Vasodilator Response in Pulmonary Arterial Hypertension

Introduction: Pulmonary arterial hypertension (PAH) is a rare and fatal disease associated with variable therapeutic response, suggesting a genetic contribution. Vasodilator-responsive PAH accounts for a minority of PAH cases and is associated with dramatically improved survival over vasodilator-nonresponsive PAH. The objective of our study was to identify genetic influences on vasodilator drug response in PAH. Methods: Two cohorts of patients with Group I PAH confirmed by right heart catheterization were derived from the PAH Biobank (NHLBI R24HL105333), representing over 40 US institutions. Differences between hemodynamics at rest (baseline mean pulmonary arterial pressure, mPAP) and after vasodilator (nitric oxide, prostacyclin) administration were determined to define acute vasodilator drug response (with unchanged cardiac index) as a continuous measure. All cases were genotyped using HumanOmni5 with single nucleotide polymorphism (SNP) call rate &gt;99%, minor allele frequency (MAF)&gt;3%, and Hardy-Weinberg p-value&gt;0.01. Analysis was restricted to cases with European ancestry. We performed linear regressions in an additive model for acute vasodilator drug response with adjustment for baseline mPAP, age, gender, and first 3 principal components. A Bonferroni-corrected alpha=5x10 -8 was used in the discovery cohort and alpha=0.05 was used in the replication cohort. Results: The discovery cohort included 434 PAH cases and the replication cohort included 49 less severe PAH cases. QQ-plots showed no evidence of genomic inflation (lambda=1.00). Association of the intronic SNP rs8057488 (MAF 0.05) in the sorting nexin 29 gene ( SNX29 ) with acute vasodilator drug response reached genome-wide significance in the discovery cohort (beta= -7.03 mmHg, p=3.39x10 -8 ). A significant association between rs8057488 and acute vasodilator drug response was also observed in the replication cohort (beta = -6.48 mmHg, p=0.03). Conclusion: These findings implicate a novel association between SNX29 variation and differential responses to vasodilator treatment in Group I PAH. While requiring further replication in a larger independent cohort, these observations advance our understanding of the molecular underpinnings in PAH.

Progression of mean pulmonary arterial pressure in idiopathic pulmonary fibrosis with mild to moderate restriction.

Elevation of mean pulmonary arterial pressure (MPAP) is associated with poor prognosis in patients with idiopathic pulmonary fibrosis (IPF), yet the progression of MPAP in patients with IPF has not been sufficiently elucidated. We evaluated serial changes in MPAP and its determinants in patients with IPF with mild to moderate restriction. We retrospectively reviewed patients with IPF who underwent initial evaluations including right heart catheterization (RHC) in our institute from May 2007 to December 2013 with follow-up RHC at least 1 year later. Patients with forced vital capacity (FVC) < 50% predicted or those with pulmonary artery wedge pressure >15 mm Hg were excluded. A total of 95 patients were included. Median follow-up time of second RHC was 1.8 years. MPAP increased significantly at follow-up (from 16.8 to 20.2 mm Hg; P < 0.001), and annual change in MPAP (ΔMPAP) was 1.8 mm Hg/year. In multiple regression analysis, the lowest oxygen saturation (SpO2 ) at 6-min walk test (6MWT) was an independent predictor of ΔMPAP. When adjusted for age, sex, baseline MPAP and FVC % predicted, ΔMPAP was a significant predictor of mortality (hazard ratio: 1.21; P = 0.001). ΔMPAP was significantly associated with desaturation in the 6MWT, and with increased mortality in patients with IPF with mild to moderate restriction.

Left Ventricular Myocardial Fibrosis, Atrophy, and Impaired Contractility in Patients With Pulmonary Arterial Hypertension and a Preserved Left Ventricular Function: A Cardiac Magnetic Resonance Study.

Using a cardiac magnetic resonance (CMR) approach we investigated left ventricular (LV) myocardial changes associated with pulmonary arterial hypertension (PAH) by strain analysis and mapping techniques. Seventeen patients with PAH (9 men; mean age, 64.2±13.6 y) and 20 controls (10 men, 63.2±10.5 y) were examined using CMR at 1.5 T. Native LV T1-relaxation times (T1) and extracellular volume fraction (ECV) were assessed using a MOLLI sequence, T2-relaxation times (T2) by means of a gradient spin-echo sequence, and LV longitudinal strain (LVS) and right ventricular (RV) longitudinal strain (RVS) by means of CMR feature tracking. The hematocrit and serum levels of pro-Brain Natriuretic Peptide were determined on the day of the CMR examination. Pulmonary arterial pressure and 6-minute walking distance were assessed as part of the clinical evaluation. T1 and ECV were higher (1048.5±46.6 vs. 968.3±22.9 ms and 32.4%±5.7% vs. 28.4%±3.8%; P<0.05) and LVS was lower in patients with PAH (-18.0±5.6 vs. -23.0±2.9; P<0.01) compared with controls. LV mass and interventricular septal thickness were lower in PAH patients (65.7±18.0 vs. 86.7±26.9 g and 7.6±1.9 vs. 10±2.4 mm; P<0.05); there were no differences in LV ejection fraction (61.2%±6.9% vs. 61.9%±6.7%; P=0.86). T1-derived parameters correlated significantly with RVS, LVS, the 6-minute walking distance, RV ejection fraction, pro-Brain Natriuretic Peptide, and baseline mean pulmonary arterial pressure. There were no significant differences in T2. In patients with PAH, changes in T1 and ECV support the hypothesis of LV myocardial fibrosis and atrophy with a consecutively impaired contractility despite a preserved LV function, possibly due to longstanding PAH-associated LV underfilling.

CMR fluoroscopy right heart catheterization for cardiac output and pulmonary vascular resistance: results in 102 patients

BackgroundQuantification of cardiac output and pulmonary vascular resistance (PVR) are critical components of invasive hemodynamic assessment, and can be measured concurrently with pressures using phase contrast CMR flow during real-time CMR guided cardiac catheterization.MethodsOne hundred two consecutive patients underwent CMR fluoroscopy guided right heart catheterization (RHC) with simultaneous measurement of pressure, cardiac output and pulmonary vascular resistance using CMR flow and the Fick principle for comparison. Procedural success, catheterization time and adverse events were prospectively collected.ResultsRHC was successfully completed in 97/102 (95.1%) patients without complication. Catheterization time was 20 ± 11 min. In patients with and without pulmonary hypertension, baseline mean pulmonary artery pressure was 39 ± 12 mmHg vs. 18 ± 4 mmHg (p < 0.001), right ventricular (RV) end diastolic volume was 104 ± 64 vs. 74 ± 24 (p = 0.02), and RV end-systolic volume was 49 ± 30 vs. 31 ± 13 (p = 0.004) respectively. 103 paired cardiac output and 99 paired PVR calculations across multiple conditions were analyzed. At baseline, the bias between cardiac output by CMR and Fick was 5.9% with limits of agreement −38.3% and 50.2% with r = 0.81 (p < 0.001). The bias between PVR by CMR and Fick was −0.02 WU.m2 with limits of agreement −2.6 and 2.5 WU.m2 with r = 0.98 (p < 0.001). Correlation coefficients were lower and limits of agreement wider during physiological provocation with inhaled 100% oxygen and 40 ppm nitric oxide.ConclusionsCMR fluoroscopy guided cardiac catheterization is safe, with acceptable procedure times and high procedural success rate. Cardiac output and PVR measurements using CMR flow correlated well with the Fick at baseline and are likely more accurate during physiological provocation with supplemental high-concentration inhaled oxygen.Trial registrationClinicaltrials.gov NCT01287026, registered January 25, 2011.