Changes In Pulmonary Vascular Resistance Research Articles

The change in pulmonary vascular resistance after left ventricular assist device implantation – the predictive role of platelets revisited

E-mail: marijan.pasalic@yahoo.com Purpose: While analyzing the group of patients implanted with a left ventricular assist device (LVAD) at our institution to verify which of the preand postoperative factors constitute the optimal survival outcome predictors, we determined a significant increase in postoperative pulmonary vascular resistance (PVR) values in the expired patients1. The aim of this study was to further analyze the data in order to determine which of the preoperative factors were related to the aforementioned increase in postoperative PVR values. Methods: For the 20 patients (18 M, 2 F; mean age 58.7±8.3 years) that have been implanted with an LVAD in our institution during the past 2 years, preimplantation echocardiography, right heart catheterization (RHC) and laboratory data were collected and compared according to the values of the postimplantation PVR. The groups were compared by using the adequate statistical test (t-test, Mann Whitney U test, statistical significance set at 0.05). Correlation analysis and linear regression were performed. Results: Among the 20 patients, 14 had postoperative RHC data and 4 of them were proven to have elevated PVR values (>2.4 WU). When comparing the pts. with elevated to those with normal PVR values, no significant difference was found neither in the RV function (FAC 33±7% vs 22±12%, TAPSE 1,0±0,7 cm vs 1.6±0.5 cm, NS), nor in the RV and LV dimensions (RVIDd 34±9 mm vs 35±12 mm, LVIDd 65±10 mm vs 73±9 mm). The borderline significance was found in the left ventricular EF (28±3% vs 19±8%, p=0.06) and the degree of the MR (median values 1 vs 2, p=0.05). The preoperative RHC parameters were not found to be predictive of changes in postoperative PVR (preoperative PVR 4,2±3,4 vs 3,4±1,5 WU, C.I. 1,8±0,7 vs 1,9±0,4 L/min/m, TPG 14±11 vs 13±4 mmHg and RVSWI 11,4±2,2 vs 8,9±2,1, NS). As for the laboratory values, only the platelet count significantly differed between the groups (128 ±73 vs 246±65 E3/mm, p<0.05). The correlation analysis showed a strong negative correlation between the platelet count and postoperative PVR values (r=-0,761, p<0.01). The linear regression verified the following relationship between the variables PVR=6,247-0,017xPLT, p<0.01). Conclusion: These preliminary data show that the platelet count is a significant predictor of the postoperative PVR values in patients with an LVAD (a previously shown survival predictor1). Further investigation will be conducted to explain the role of platelets in the etiology of PVR in our group of pts.

STUDY ON PULMONARY VASCULAR RESISTANCE BY ECHOCARDIOGRAPHY IN PATIENTS WITH MITRAL STENOSIS

Objective: assessing changes in pulmonary vascular resistance by Doppler ultrasound in patients with mitral stenosis who had pulmonary hypertension and evaluating the relationship between pulmonary vascular resistance with the degree of heart failure (NYHA), mitral valve area and systolic pulmonary pressure. Methods: 56 patients with mitral stenosis were admitted to the Department of Cardiology, Hue Central Hospital. The Doppler ultrasound was maded in all patients. Results: The proportion of patients with pulmonary vascular resistance ≥ 2 Wood UI is 83,90%. Pulmonary vascular resistance in group with mild mitral stenosis was 2.55 ± 0.97 (Wood), in group with moderate mitral stenosis was 2.71 ± 1.27 (Wood) and in group with severe mitral stenosis was 3.70 ± 1, 24 (Wood). Pulmonary vascular resistance in the group with mild pulmonary hypertension was 2.80 ± 0.84 (Wood), moderate pulmonary hypertension was 2.96 ± 0.40 (Wood) and severe pulmonary hypertension was 4.73 ± 1.40 (Wood). There is a positive correlation between pulmonary vascular resistance with heart failure according to the NYHA classification (r=0.58 p&lt;0.0001), systolic pulmonary artery pressure (r = 0.79 and p &lt;0, 0001). There was a negative correlation between pulmonary vascular resistance with mitral valve area (r = -0.57 p &lt;0.0001). Conclusions: We found a good correlation between the pulmonary vascular resistance by Echo –Doppler and the severity of mitral stenosis, systolic pulmonary pressure, NYHA classification. Keywords: Pulmonary vascular resistance; mitral stenosis.

Vascular hyperreactivity in a rat model of bronchopulmonary dysplasia (715.2)

Bronchopulmonary dysplasia (BPD) develops in ~30% of premature infants and is associated with decreased alveolar and vascular development. We hypothesized that BPD is also associated with vascular hyperreactivity to hypoxic and hyperoxic challenges. A rat model of BPD was created by exposing newborn Sprague Dawley rats to 95% O2 (BPD) for 8 days after birth. Controls (CTL) were exposed to 21% O2. At 21‐25 days old, rats were anesthetized and a Millar conductance catheter was inserted into the left ventricle to obtain cardiac output. A fluid‐filled catheter was inserted into the right ventricle (RV) to measure pressure. Rats were ventilated with 100% O2 (10 min), and 10% O2 (10 min) and pulmonary vascular resistance (PVR) was calculated for each condition by dividing the RV pressure by cardiac output. BPD rats had RV hypertension at baseline compared to CTL (31±5 mmHg vs 16±2 mmHg, p=0.028), largely caused by increased cardiac output. Contrary to our hypothesis, BPD rats demonstrated little change in PVR to hypoxia and hyperoxia, suggesting that vascular reactivity is impaired in BPD. Given the observed baseline RV hypertension in the BPD group, our future studies will aim to investigate the impact on myocardial contractility in this model.Grant Funding Source: Supported by NIH 5R01HL115061

Bosentan for Sarcoidosis-Associated Pulmonary Hypertension: A Double-Blind Placebo Controlled Randomized Trial

<h3>Background</h3> Sarcoidosis-associated pulmonary hypertension (SAPH) is a common problem in patients with persistent dyspneic sarcoidosis. The objective of this study was to determine the effect of bosentan therapy on pulmonary arterial hemodynamics in patients with SAPH. <h3>Methods</h3> This 16-week study was a double-blind, placebo-controlled trial of either bosentan or placebo in patients with SAPH confirmed by right-sided heart catheterization. Patients were enrolled from multiple academic centers specializing in sarcoidosis care. They were stable on sarcoidosis therapy and were receiving no therapy for pulmonary hypertension. The cohort was randomized two to one to receive bosentan at a maximal dose of 125 mg or placebo bid for 16 weeks. Pulmonary function studies, 6-min walk test, and right-sided heart hemodynamics, including pulmonary artery mean pressure and pulmonary vascular resistance (PVR), were performed before and after 16 weeks of therapy. <h3>Results</h3> Thirty-five patients completed 16 weeks of therapy (23 treated with bosentan, 12 with placebo). For those treated with bosentan, repeat hemodynamic studies at 16 weeks demonstrated a significant mean ± SD fall in PA mean pressure (−4 ± 6.6 mm Hg, <i>P</i> = .0105) and PVR (−1.7 ± 2.75 Wood units, <i>P</i> = .0104). For the patients treated with placebo, there was no significant change in either PA mean pressure (1 ± 3.7 mm Hg, <i>P</i> > .05) or PVR (0.1 ± 1.42 Wood units, <i>P</i> > .05). There was no significant change in 6-min walk distance for either group. Two patients treated with bosentan required an increase of supplemental oxygen by > 2 L after 16 weeks of therapy. <h3>Conclusions</h3> This study demonstrated that bosentan significantly improved pulmonary hemodynamics in patients with SAPH. <h3>Trial registry</h3> ClinicalTrials.gov; No: NCT00581607; URL: www.clinicaltrials.gov

(716) - The Change in Pulmonary Vascular Resistance After LVAD Implantation - Can It Aid in Predicting Postimplantation Survival?

(716) - The Change in Pulmonary Vascular Resistance After LVAD Implantation - Can It Aid in Predicting Postimplantation Survival?

Right ventricular reverse remodelling after balloon pulmonary angioplasty

Balloon pulmonary angioplasty (BPA) has been reported to improve haemodynamics and functional capacity, with an acceptable risk, in patients with chronic thromboembolic pulmonary hypertension (CTEPH) who are not candidates for pulmonary endarterectomy. However, right ventricular (RV) function, an important predictor in CTEPH, remains to be elucidated. We aimed to examine the impact of BPA on RV remodelling and dysfunction relative to haemodynamic improvements in patients with inoperable CTEPH. 20 consecutive patients with inoperable CTEPH who underwent BPA with cardiovascular magnetic resonance before and after BPA were retrospectively studied. BPA led to significant amelioration of the mean pulmonary arterial pressure, cardiac index and pulmonary vascular resistance (PVR), without death or major complications. Furthermore, BPA significantly ameliorated right-sided heart failure symptoms and signs, and exercise capacity. Cardiovascular magnetic resonance revealed a marked improvement in RV end-diastolic and end-systolic volume index, with concomitant improvements in RV ejection fraction, mass and interventricular septal bowing after BPA. Changes in RV volumes strongly correlated with changes in cardiac index and PVR. BPA induced RV reverse remodelling and improved systolic dysfunction safely by ameliorating haemodynamics in patients with inoperable CTEPH. Evaluating RV function with cardiovascular magnetic resonance may be effective for noninvasively monitoring BPA efficacy.

Variation in platelet response may affect the hemodynamic response to vasoreactivity testing in patients with secondary pulmonary hypertension due to left heart disease

Cardiologia CROATICA Objectives: Pulmonary hypertension (PH) and vascular resistance in patients with pulmonary arterial hypertension (PAH) are caused by remodeling and thrombosis of small and medium sized pulmonary arteries and arterioles, as well as vasoconstriction. These patients have increased platelet aggregation and the activated platelets are major source of thromboxane A2 which is a strong vasopressor and proaggregation molecule. PGI2 and PGE1 have opposite effects. Misbalance in eicosanoids synthesis was observed in patients with PH. The results from vasoreactivity test, in which we measure the hemodynamic response to vasodilator, particularly change in mean pulmonary pressure (mPAP), pulmonary vascular resistance (PVR) and transpulmonary gradient (TPG) in patients with PH due to the left heart disease, influence the decision on future course of treatment. The goal: to test whether the change of platelet aggregation during vasoreactivity testing is related to hemodynamic response measured as the change in mPAP, PVR and TPG. Patients and Methods: Our pilot study included 38 patients with secondary PH due to the left heart disease, 29 men (76%) and 9 women (24%). The right heart catheterization was performed in all patients and vasoreactivity testing with PGE1 in 19 patients (50%). Platelet aggregation induced by addition of AA (ASPI test), ADP (ADP test) and collagen (COL-test) was measured in blood samples from pulmonary artery with Multiplate and repeated after vasoreactivity testing. Results: Patients with the reduction of platelet aggregation in ASPI test had stronger, but insignificant reduction in mPAP (p=0.08) and PVR (p=0.15). Significant reduction was observed in the reduction of TPG (p=0.03). The reduction of platelet aggregation in ADP test was not related to hemodynamic response to PGE1. Patients with the reduction of aggregation in collagen test had stronger, though insignificant reduction in mPAP (p=0.08). However, they had significant reduction in PVR (p=0.01) and TPG (p=0.05) in comparison to those with increased aggregation. Conclusion: The data analysis in our pilot study shows insufficient size of the sample to reach a final conclusion. However, it suggest a significant potential difference in vasoreactivity among patients who respond with a decrease and those who respond with an increase in platelet aggregation after testing with PGE1. We hypothesize that variations in platelet response to PGE1 modulate its hemodynamic effect on pulmonary circulation.

Effect of Optison on Pulmonary Artery Systolic Pressure and Pulmonary Vascular Resistance

Ultrasound contrast agent safety has received recent attention based on reports of associated serious adverse events. The US Food and Drug Administration requested this postmarketing study of the effects of Optison on pulmonary hemodynamics. The aim of this study was to compare Optison and a placebo for effects on pulmonary artery systolic pressure (PASP) and pulmonary vascular resistance (PVR) during right-sided cardiac catheterization. This was a single-blind, crossover, placebo-controlled, multicenter study of Optison in subjects referred for clinically indicated cardiac catheterization. Based on screening echocardiographic PASP, subjects were assigned to 1 of 2 strata (1 = normal PASP [≤35 mm Hg] and 2 = elevated PASP [>35 mm Hg]), in which they were randomized to treatment arm A (intravenous 0.5 ml Optison and then intravenous 0.5 ml placebo [5% dextrose] 15 minutes later) or arm B (intravenous 0.5 ml placebo [5% dextrose] and then 0.5 ml Optison 15 minutes later). Baseline pulmonary hemodynamics were obtained within 60 minutes before the first injection and 2, 6, and 10 minutes after each injection. Thirty patients each received their assigned treatments. There were no clinically relevant increases from baseline in mean PASP or PVR (Wood units) in either stratum alone or the combined strata. There were no serious adverse events. In conclusion, there is no change in PASP or PVR after intravenous injection of Optison at a clinically relevant dose in patients with normal or elevated baseline PASP.

Utility of right ventricular Tei-index for assessing disease severity and determining response to treatment in patients with pulmonary arterial hypertension

BackgroundWe sought to evaluate the potential utility of echocardiography-derived morphological and functional right ventricular (RV) variables for assessing disease severity of pulmonary arterial hypertension (PAH) and determining the changes in the patient's hemodynamics in the clinical course. Methods and resultsThis study consisted of 24 normal controls (the control group) and 24 patients with PAH at rest or with exercise (the PAH group) who underwent echocardiography, right heart catheterization, plasma brain natriuretic peptide (BNP) measurement, and six-minute walk distance (6MWD) test. The PAH group had poorer RV echocardiographic variables than the control group. RV Tei-index was more strongly correlated with 6MWD, BNP, cardiac index, mean pulmonary arterial pressure, and pulmonary vascular resistance (PVR) than other RV echocardiography-derived variables including RV end-diastolic areas, RV fractional area change, and tricuspid annular plane systolic excursion. In 16 of the 24 patients who successfully underwent repeated examination during follow up (13.3±4.9 months; range, 5–24 months), PVR decreased from 486±380dynescm−5 to 346±252dynescm−5, and RV Tei-index decreased from 0.55±0.30 to 0.42±0.17, and the changes in RV Tei-index were correlated with the concomitant changes in PVR during the clinical course of PAH (r=0.706, p=0.002). Tricuspid annular plane systolic excursion and RV fractional area change did not change during the follow up. ConclusionsQuantitative echocardiography revealed that the measurement of RV Tei-index is of great clinical utility for predicting disease severity of PAH and determining the changes in the patient's hemodynamics in the clinical course.

Estimation of Blood Flow Resistance in the Lung with MRI

Cardiac magnetic resonance can be used to monitor pulmonary vascular resistance changes in animal models of pulmonary hypertension.

Noninvasive Monitoring of Serial Changes in Pulmonary Vascular Resistance and Acute Vasodilator Testing Using Cardiac Magnetic Resonance

The study sought to evaluate the ability of cardiac magnetic resonance (CMR) to monitor acute and long-term changes in pulmonary vascular resistance (PVR) noninvasively. PVR monitoring during the follow-up of patients with pulmonary hypertension (PH) and the response to vasodilator testing require invasive right heart catheterization. An experimental study in pigs was designed to evaluate the ability of CMR to monitor: 1) an acute increase in PVR generated by acute pulmonary embolization (n = 10); 2) serial changes in PVR in chronic PH (n = 22); and 3) changes in PVR during vasodilator testing in chronic PH (n = 10). CMR studies were performed with simultaneous hemodynamic assessment using a CMR-compatible Swan-Ganz catheter. Average flow velocity in the main pulmonary artery (PA) was quantified with phase contrast imaging. Pearson correlation and mixed model analysis were used to correlate changes in PVR with changes in CMR-quantified PA velocity. Additionally, PVR was estimated from CMR data (PA velocity and right ventricular ejection fraction) using a formula previously validated. Changes in PA velocity strongly and inversely correlated with acute increases in PVR induced by pulmonary embolization (r = -0.92), serial PVR fluctuations in chronic PH (r = -0.89), and acute reductions during vasodilator testing (r = -0.89, p ≤ 0.01 for all). CMR-estimated PVR showed adequate agreement with invasive PVR (mean bias -1.1 Wood units,; 95% confidence interval: -5.9 to 3.7) and changes in both indices correlated strongly (r = 0.86, p < 0.01). CMR allows for noninvasive monitoring of acute and chronic changes in PVR in PH. This capability may be valuable in the evaluation and follow-up of patients with PH.

Riociguat for the Treatment of Pulmonary Arterial Hypertension

BackgroundRiociguat, a soluble guanylate cyclase stimulator, has been shown in a phase 2 trial to be beneficial in the treatment of pulmonary arterial hypertension.MethodsIn this phase 3, double-blind study, we randomly assigned 443 patients with symptomatic pulmonary arterial hypertension to receive placebo, riociguat in individually adjusted doses of up to 2.5 mg three times daily (2.5 mg–maximum group), or riociguat in individually adjusted doses that were capped at 1.5 mg three times daily (1.5 mg–maximum group). The 1.5 mg–maximum group was included for exploratory purposes, and the data from that group were analyzed descriptively. Patients who were receiving no other treatment for pulmonary arterial hypertension and patients who were receiving endothelin-receptor antagonists or (nonintravenous) prostanoids were eligible. The primary end point was the change from baseline to the end of week 12 in the distance walked in 6 minutes. Secondary end points included the change in pulmonary vascular resistance, N-terminal pro–brain natriuretic peptide (NT-proBNP) levels, World Health Organization (WHO) functional class, time to clinical worsening, score on the Borg dyspnea scale, quality-of-life variables, and safety.ResultsBy week 12, the 6-minute walk distance had increased by a mean of 30 m in the 2.5 mg–maximum group and had decreased by a mean of 6 m in the placebo group (least-squares mean difference, 36 m; 95% confidence interval, 20 to 52; P<0.001). Prespecified subgroup analyses showed that riociguat improved the 6-minute walk distance both in patients who were receiving no other treatment for the disease and in those who were receiving endothelin-receptor antagonists or prostanoids. There were significant improvements in pulmonary vascular resistance (P<0.001), NT-proBNP levels (P<0.001), WHO functional class (P=0.003), time to clinical worsening (P=0.005), and Borg dyspnea score (P=0.002). The most common serious adverse event in the placebo group and the 2.5 mg–maximum group was syncope (4% and 1%, respectively).ConclusionsRiociguat significantly improved exercise capacity and secondary efficacy end points in patients with pulmonary arterial hypertension. (Funded by Bayer HealthCare; PATENT-1 and PATENT-2 ClinicalTrials.gov numbers, NCT00810693 and NCT00863681, respectively.)

Utility of Electrocardiogram in the Assessment and Monitoring of Pediatric Pulmonary Hypertension

Purpose Adult studies have shown utility of ECGs in disease stratification and monitoring in pulmonary hypertension (PH). We sought to identify the ECG findings that are present in pediatric PH and correlate with disease severity and change over time. Methods and Materials We retrospectively identified all patients ≤21 years old with PH (Dana Point 1.1 and 3.7) confirmed by catheterization (cath) and had an ECG within 60 days of cath. ECG and cath findings included: right axis deviation (RAD); right atrial enlargement (RAE); right ventricular hypertrophy (RVH) and strain; pulmonary artery pressure (PAP) and capillary wedge pressure; right atrial pressure; cardiac index; and indexed pulmonary vascular resistance (PVR). A change in PVR of ≥20% was deemed significant between caths. Results We identified 48 patients (46% group 1.1), yielding 107 cath-ECG pairs. Median age at cath was 49 months (IQR: 4-202). Median PVR was 7.2 WU/m2 (2.2-27.9). Of the 107 pairs, 94% had ECG abnormalities: 54% with RAD; 80% with RVH; 57% with a rSR’/qR in V1/V4R; 19% with RAE; and 3% with bundle branch block. Individual ECG parameters weakly correlated with PVR and the transpulmonary gradient (TPG). Combination of RAD and RVH significantly correlated with PVR (β=3.9), PAP (β=14.8), and TPG (β=15.1), (p Conclusions ECG abnormalities are common in pediatric PH. RAD and RVH on ECG was associated with worse hemodynamics, while their absence predicted a lack of disease progression.

Continuous Flow Left Ventricular Assist Devices Improve Survival in Reactive but Not Fixed Type 2 Pulmonary Hypertension Compared with Medical Therapy

Purpose Left heart failure is often complicated by pulmonary hypertension (T2PH), which can progress from ‘reactive' (RPH) to a'fixed' (FPH), significantly increasing morbidity and mortality. Continuous flow left ventricular assist devices (VAD) can reverse T2PH. We aimed to determine if treatment with VAD therapy improves morbidity and mortality in T2PH in both RPH and FPH. Methods and Materials All right heart catheters were analysed from Jan 2008 to Oct 2012 in our institution. Selection criteria: cardiac index 2.8 l/min/m 2 , pulmonary capillary wedge pressure>15mmHg, mean pulmonary arterial pressure>25mmHg, and transpulmonary gradient>15mmHg OR pulmonary vascular resistance (PVR)>3.0WU. FPH group had TPG>15 or PVR>3.0 after vasodilator challenge. Baseline and follow-up data were analysed. Results 62 patients had T2PH (15FPH, 47 RPH). 21 had VAD therapy (6FPH, 15RPH), and 41 medical therapy (9 FPH, 32 RPH). PVR was significantly reduced by VAD but not medical therapy [Table 1]. Cardiovascular admissions were reduced byVAD cf medical therapy (p Conclusions VAD therapy significantly improves survival in T2PH patients with RPH. Patients with FPH benefited from VAD therapy by having reduced hospital admissions but this study did not show a survival benefit. LVADMedicalFPH (n=6)RPH (n=15)FPH (n=9)RPH (n=32)NYHA4433INTERMACS1177002070036640110417465695-7003323PVR pre-treatment7.26.356.85.1PVR post-treatment3.82.116.24.6p-value (PVR change)

Tracheal occlusion alters pulmonary circulation in the fetal lamb with normally developing lungs

BackgroundTracheal occlusion (TO) promotes fetal lung growth through an increase in intraluminal pressure. Although evidence suggests that fetal TO (FETO) decreases the occurrence of pulmonary hypertension in severe congenital diaphragmatic hernia, controversies on its effect on the pulmonary circulation remain. Therefore, we investigated the effects of FETO on the lung hemodynamics in a chronically catheterized fetal lamb model. MethodsFifteen pregnant ewes were operated on between 125 and 128days of gestation (term: 145days). Catheters and ultrasonic flow transducer were placed through a left thoracotomy in the lamb fetus to determine aortic, pulmonary and left atrial pressures, and left pulmonary artery blood flow. A balloon was positioned between the carina and vocal cords under fetoscopic control. The animals were assigned to either control (n=6) or FETO (n=9) groups. TO was performed by inflating the balloon. We studied the acute effects of temporary (2-h) and prolonged (4-day) TO on basal pulmonary vascular tone and on the pulmonary vascular reactivity to acetylcholine and to increased fetal oxygen tension. ResultsWe found that left pulmonary blood flow (LPA) increased and pulmonary vascular resistance (PVR) decreased by 20% during brief TO (p<0.05). After balloon deflation, LPA blood flow further increased by 40%, and PVR decreased by 50% compared to baseline values (p<0.05). In contrast, no change in LPA blood flow or PVR was observed during prolonged TO. Moreover, the vasodilator responses to acetylcholine and to increased fetal PaO2 were blunted during TO. ConclusionsThese data indicate that antenatal tracheal occlusion promotes active pulmonary vasodilation, which is partly blunted by the mechanical effects of elevation of the intraluminal pressure.

Pulmonary circulatory changes after bilateral total knee arthroplasty during regional anesthesia

Study ObjectiveTo monitor the pulmonary hemodynamics of patients undergoing bilateral total knee arthroplasty (BTKA) intraoperatively and up to 24 hours following surgery. DesignProspective observational study. SettingUniversity-affiliated teaching hospital. Patients30 ASA physical status 2 and 3 patients scheduled for single-stage, cemented BTKA during epidural anesthesia. InterventionsPulmonary artery catheters were in all patients. MeasurementsSystemic vascular resistance (SVR), pulmonary vascular resistance (PVR), the ratio of PVR to SVR at baseline, at the beginning of surgery, and after each knee implantation were recorded and compared with measurements taken one day postoperatively (POD 1). Main ResultsOn POD 1, PVR/SVR was increased by 30% compared with baseline (P < 0.0001) and by 20% versus the end of surgery (P < 0.0001). Systemic vascular resistance decreased during surgery and was significantly lower than baseline at 24 hours after surgery (P < 0.0001). No significant change in PVR was noted during surgery. ConclusionThe PVR/SVR ratio on the day following BTKA was increased. This change may represent the different effects of inflammatory perioperative stresses on the pulmonary and systemic vasculature.

Brief Report: Effect of ambrisentan treatment on exercise‐induced pulmonary hypertension in systemic sclerosis: A prospective single‐center, open‐label pilot study

Exercise-induced pulmonary hypertension (ePH) may represent an early, clinically relevant phase in the spectrum of pulmonary vascular disease. The purpose of this pilot study was to describe the changes in hemodynamics and exercise capacity in patients with systemic sclerosis (SSc) spectrum-associated ePH treated with open-label daily ambrisentan. Patients were treated with ambrisentan, 5 mg or 10 mg once daily, for 24 weeks. At baseline and 24 weeks, patients with SSc spectrum disorders exercised in a supine position, on a lower extremity cycle ergometer. All patients had normal hemodynamics at rest. We defined baseline ePH as a mean pulmonary artery pressure of >30 mm Hg with maximum exercise and a transpulmonary gradient (TPG) of >15 mm Hg. The primary end point was change in pulmonary vascular resistance (PVR) with exercise. Secondary end points included an improvement from baseline in 6-minute walking distance, health-related quality of life assessments, and cardiopulmonary hemodynamics. Of the 12 enrolled patients, 11 completed the study. At 24 weeks there were improvements in mean exercise PVR (85.8 dynes × second/cm(5) ; P = 0.003) and mean distance covered during 6-minute walk (44.5 meters; P = 0.0007). Improvements were also observed in mean exercise cardiac output (1.4 liters/minute; P = 0.006), mean pulmonary artery pressure (-4.1 mm Hg; P = 0.02), and total pulmonary resistance (-93.0 dynes × seconds/cm(5) ; P = 0.0008). Three patients developed resting pulmonary arterial hypertension during the 24 weeks. Exercise hemodynamics and exercise capacity in patients with SSc spectrum-associated ePH improved over 24 weeks with exposure to ambrisentan. Placebo-controlled studies are needed to confirm whether this is a drug-related effect and to determine optimal therapeutic regimens for patients with ePH.

Abstract 18354: Cardiac Magnetic Resonance Allows Noninvasive and Accurate Monitoring of Serial Changes in Pulmonary Vascular Resistance and the Acute Vasodilator Response in Chronic Pulmonary Hypertension

Background: Monitoring pulmonary vascular resistance (PVR) during the follow-up of patients with pulmonary hypertension (PH) and the acute vasodilator response require invasive right heart catheterization. A noninvasive method would be valuable. Hypothesis: Cardiac magnetic resonance (CMR) allows noninvasive monitoring of PVR and the acute vasodilator response. Methods: Two experimental models of chronic PH were developed in pigs. A precapillary PH model was induced by repeated pulmonary embolization with microspheres (n=8). A postcapillary PH model was generated with surgical banding of the main pulmonary vein (n=10). At baseline and every month, animals were evaluated by CMR (pulmonary artery mean flow velocity [PAvel] from phase-contrast images) with simultaneous invasive quantification of PVR using a CMR-compatible Swan-Ganz catheter (N=60 pairs of measurements). Generalized estimating equations analysis was used to correlate repeated measurements of PVR and PAvel. Additionally, correlation between acute changes in PAvel and PVR induced by pulmonary embolization (n=10) or vasodilator administration (n=10) inside the magnet was assessed using Spearman correlation. Results: Both models generated chronic PH (mPAP=30.8±4.8 and 54.5±12.8, pre and postcapillary respectively) with typical changes on pathology. CMR-model based on PAvel strongly correlated with serial measurements of PVR in both precapillary (r=0.86, p&lt;0.01) and postcapillary (r=0.97, p&lt;0.01, examples in figure A) models. Additionally, acute changes in PAvel were strongly correlated with the increase in PVR induced by acute embolization (r=-0.98, p&lt;0.001, figure B) or the fall in PVR produced by vasodilator testing (r=-0.89, p&lt;0.001, figure C). Conclusions: CMR allows noninvasive and accurate monitoring of acute and chronic changes in PVR and the acute vasodilator response in a broad spectrum of PH. This may be very valuable for the evaluation and follow-up of patients with PH.

Abstract 18676: Early Changes of Pulmonary Vascular Remodelling After Pulmonary Thrombendarterectomy Measured by Cardiac MRI

Purpose: Chronic Thrombembolic Hypertension (CTEPH) occurs in about 3.8% of patients with acute pulmonary embolism. The longterm prognosis is poor, however pulmonary thrombendarterectomy (PEA) offers a potential cure with excellent outcome. Several surrogate markers of pulmonary vascular remodelling have been defined. The max. PA velocity and acceleration time (AT) or its equivalent normalised over ejection times (AT/ET) reflect pulmonary pressure, the relative area change of the PA (RAC) and PA-flow-contour analysis derived dicrotic notch are indicative of changes of pulmonary vascular resistance (PVR). All these parameters can be measured excellently by cardiac magnetic resonance (CMR). In the present study we sought to quantitate surrogate markers of pulmonary vascular remodelling and reverse remodelling before and after PEA by CMR. Methods: patients underwent CMR 2 ± 1 day before and 10 ± 2 days after PEA. Flow/Time curves, PA area and PA max. velocity were derived from Phase-Contrast velocity encoded gradient echo sequences. The temporal resolution was adjusted to 11 ms, sequences were acquired with three signal averages in free breathing to allow for longer acquisition times needed for increased temporal resolution. All numerical data are presented as means ± SD, differences were tested with t-test for paired data, differences in frequencies were tested with McNemar's test. Results: 65 patients were included, mean age 56 ± 16, 28 females. PA peak velocity improved from 61 ± 17 cm/s to 74 ± 19, p = 0.001, AT/ET improved from 0.32 ± 0.06 to 0.36 ± 0.09, p = 0.002, RAC showed a trend to lower values and decreased from 29 ± 1.9% to 25 ± 1.2%, p = 0.1, a diastolic notch was found in 51 of 65 patients before PEA and only in 12 of 65 patients post surgery, p = 0.0001. In those patients in which the notch persisted, there was a trend to smaller notch ratios post PEA 1.37 ± 0.17 vs. 1.12 ± 0.24, p = 0.06. Conclusion: CMR is an excellent tool to monitor pulmonary vascular remodelling after PEA for CTEPH. We were able to demonstrate improved surrogate markers of PA pressure and resistance as early as 10 days after PEA in a large series of 65 patients.

Acute haemodynamic response in relation to plasma vardenafil concentrations in patients with pulmonary hypertension

To evaluate the acute haemodynamic effects of a single oral dose of vardenafil and to study the drug concentration in relation to haemodynamic effects in patients with pulmonary hypertension (PH). Sixteen patients with PH (aged 29-85\ years), received one single oral dose of vardenafil (5, 10 or 20 mg). The haemodynamic effect was assessed over a 60 min period. Vardenafil plasma concentrations were measured after 15, 30, 45 and 60 min using liquid chromatography-tandem mass spectrometry. At 60 min a reduction in mPAP with a median % decrease of -20.3% (range -48.3 to 3.0; P < 0.001) and an increase in cardiac output and the cardiac index with a median % change of 10.6% (range -25.0 to 88.1; P = 0.015) and 12.1% (range -24.0 to 94.4; P = 0.01) respectively was observed. The pulmonary vascular resistance (PVR) was reduced with a median % decrease of -28.9% (range -61.5 to -5.9; P < 0.001), and pulmonary selectivity was reflected by a median percent reduction of -16.9% (range -49.0 to 16.5; P = 0.002; n = 14) in the PVR/systemic vascular resistance ratio. There was a correlation between the plasma concentrations of vardenafil and change in mPAP (r = -0.579, P = 0.019) and between vardenafil concentrations and change in PVR (r = -0.662, P = 0.005). Vardenafil causes rapid changes in cardiopulmonary haemodynamics and there is a correlation between plasma vardenafil drug concentration and the acute changes in mPAP as well as PVR in patients with PH.