Pulmonary Pulse Pressure Research Articles

In vivo study of pulmonary artery remodeling and pulsatility in long Fontan patient

Abstract Background Pulmonary vasculopathy associated with Fontan circulation is a relatively unexplored entity that could have clinical and therapeutic implications. Purpose Our aim was to evaluate the physiology of the pulmonary artery in patients with Fontan circulation using conventional right heart catheterization (RHC) and intravascular ultrasound (IVUS). Methods From December 2022 to January 2024, data from all consecutive Fontan patients undergoing RHC were prospectively collected at a tertiary referral center for adult congenital heart disease. Pressures and pulmonary artery wall high-definition IVUS recordings (OptiCrossTM, 60 MHz, Boston Scientific) were recorded at rest and during apnea. Pathological Fontan pressure was defined when as exceeding 15 mmHg. IVUS pulsatility index was defined as [(systolic lumen area - diastolic lumen area)/(diastolic lumen area) ×100], Peterson's elastic modulus as (pulmonary pulse pressure/IVUS pulsatility index), and area of wall thickness as [(wall area - lumen area)/(lumen area) x100)]. In the literature, the mean ± standard deviation (SD) normal values of elastic modulus and wall thickness area have been reported as 21 ± 1.7 mmHg and 1.4 ± 1.3%, respectively, in healthy patients without pulmonary hypertension (1: doi: 10.1186/s12931-017-0568-z). We define an alteration in intrinsic pulmonary arterial wall viscoelastic properties as an elastic modulus > 70 mmHg, and we define structural pulmonary wall remodeling as an increase in wall thickness area greater than 5%. Results 13 patients were studied. Median age was 28.1 years interquartile range (IQR) (25.6- 41.4), 7 (53.9%) were female, and 4 (30,8%) were in functional New York Heart Associtation (NYHA) class I. RHC and pulmonary arterial wall IVUS values are presented in Figure 1. 6 (46.2%) had Fontan abnormal pressures at rest. All patients showed minimal pulse pressure in the pulmonary arteries synchronized with heart rate, median pulmonary pulse pressure (IQR) 3 (2-4) mmHg. This pulsatility was detected in the IVUS study in all patients, pulsatility index (median (IQR) 4.8 (3.3-10.1)) and elastic modulus (median (IQR) 51.5 (20.5-101.6) mmHg). All of them had some degree of structural pulmonary wall remodeling (>5% wall thickness area), and 10 (76.9%) of them had marked remodeling (> 10%). The median (IQR) of wall thickness area was 13.6 (10.5-18.3) % (Figure 2). We think that the pseudo-normality of the elastic modulus is due to a low pulmonary pulse pressure, however, structural remodeling could be secondary to the endothelial dysfunction present and described in arteries with very low pulsatility. Conclusions The IVUS evaluation of the pulmonary artery in Fontan patients may be useful for revealing significant information regarding pulmonary physiology. Pulmonary wall thickening has been observed, providing insight into altered structural remodeling of the pulmonary arteries in this population.

Derivation of Stroke Volume from Pulmonary Artery Pressures.

Intermittent cardiac output (CO) studies using thermodilution are considered the gold standard. We have developed a stroke volume (SV) calculator from pulmonary pulse pressure (PP) to allow continuous monitoring of SV and CO from PP. Hemodynamic data on 169 patients following orthotopic heart transplantation were used to compare our calculator-derived SV (and SV index, or SVi) against thermodilution-derived SV on admission into intensive care unit immediately following heart transplantation (T0) and 6h after admission (T6). The calculated SV correlated with thermodilution-derived SV T0 (r = 0.920, p < 0.001, coefficient of 0.539 and the constant of 2.06). The median calculator SV, adjusted for coefficient and constant, was 48.4ml (37.7, 60.7), comparable to the median thermodilution-derived SV 47.9ml (37.5, 61.0), p = 0.737 with acceptable agreement on Bland-Altman plots. The thermodilution-derived SVi was 28.1ml (19.7, 38.7) and adjusted calculator-derived SVi 28.9ml (19.7, 39.9), p = 0.781. At T6, median thermodilution-derived SVi was 27.7ml (19.5, 35.9) compared to the calculator-derived SVi median of 26.1ml (17.7, 37.7), p = 0.203. Changes in PP can be used to track changes in SV using this calculator. Changes in PP may be used to assess response to treatment in the early post-operative period.

Proportional pulmonary pulse pressure: A new index to assess response to veno-arterial extracorporeal membrane oxygenation.

Based on theoretical physiology, the ratio of pulmonary artery pulse pressure to mean pulmonary pressure (PP-MPAP), termed proportional pulmonary pulse pressure, provides a measure of coupling between the right ventricle and the pulmonary circulation. This study tested the hypothesis that lower PP-MPAP ratio was associated with left ventricular (LV) distension in patients with cardiogenic shock who underwent extracorporeal life support (ECLS). This is a retrospective observational single-centre study of 22 patients with cardiogenic shock who underwent ECLS as the primary support modality without and with LV distension and Impella unloading. The relationship between post-support PP-MPAP and 12-hour lactate clearance was also assessed. Of the 22 patients: 10 patients underwent additional Impella unloading due to LV distension (Group 1) and 12 patients on ECLS only without LV distension (Group 2). As predicted by the theoretical model, PP-MPAP on ECLS dropped in Group 1 (pre-Impella) from 0.473 ± 0.067 to 0.372 ± 0.087, p < 0.001; but increased in Group 2 patients without LV distension (0.518 ± 0.070 to 0.549 ± 0.072, p = 0.002). Impella support in Group 1 increased PP-MPAP (0.372 ± 0.087 to 0.615 ± 0.094, p < 0.001). On multiple regression analysis, post-support PP-MPAP was significantly associated with 12-hour lactate clearance. Changes in PP-MPAP is associated hemodynamic response to ECLS and 12-hour lactate clearance. This simple parameter may guide therapeutic optimization in cardiogenic shock and ECLS.

Proportional Pulmonary Artery Pulse Pressure Identifies Hemodynamic Response to Impella: Conceptualization and Clinical Validation

<h3>Purpose</h3> <b>1.</b> To describe the physiologic determinants of proportional pulmonary artery pulse pressure (= ratio of pulmonary pulse pressure to mean pulmonary pressure, PP-MPAP) <b>2.</b> clinical application of PP-MPAP in patients with cardiogenic shock (CS) who underwent left-sided Impella support. <h3>Methods</h3> <b>1.</b> Using established physiologic concepts and prior data, the change in PP-MPAP a was modelled over a range of hemodynamic parameters (Matlab, Mathworks). <b>2.</b> 16 patients with CS who underwent Impella support were included. Hemodynamic responder was defined as increase in cardiac power output index (CPOi)>20%. Clinical endpoint was lactate clearance 12 hours after Impella support. <h3>Results</h3> <b>1.</b> The relationship between stroke volume at different heart rates and PAWP was modelled [FIGURE]. <b>2.</b> 16 patients were included (age: 50±7 years; 13/16 males; 9/16 acute MI; 7/16 cardiomyopathy; LVEF: 17±4%). Impella reduced PAWP in all patients, but only 6/16 patients were responders. As predicted by the model, PP-MPAP increased in responders but dropped in non-responders. The increase in PP-MPAP correlated with increase in CPOi. The 10 non-responders were escalated to Ecpella (3(2-5)hours post-Impella), which increased PP-MPAP [TABLE]. 12-hour lactate clearance was greater in responders despite escalation to Ecpella in non-responders. Post-support PP-MPAP and the change in PP-MPAP were significantly associated with 12-hour lactate clearance. <h3>Conclusion</h3> PP-MPAP has a predictable relationship with stroke volume, and can identify hemodynamic responders to Impella, who had higher 12-hour lactate clearance.

Oral treprostinil improves pulmonary vascular compliance in pulmonary arterial hypertension

Oral treprostinil has been shown to improve exercise capacity and delay disease progression in patients with pulmonary arterial hypertension (PAH), but its effects on hemodynamics are not well-characterized. The FREEDOM-EV trial was a Phase III, international, placebo-controlled, double-blind, event-driven study in 690 participants with PAH who were taking a single oral PAH therapy. FREEDOM-EV demonstrated a significantly reduced risk for clinical worsening with oral treprostinil taken three times daily and did not uncover new safety signals in PAH patients. Sixty-one participants in the FREEDOM-EV trial volunteered for a hemodynamics sub-study. Pulmonary artery compliance (PAC), a ratio of stroke volume to pulmonary pulse pressure, significantly increased from Baseline to Week 24 in the oral treprostinil group compared with the placebo group (geometric mean 26.4% active vs. -6.0% placebo; ANCOVA p=0.007). There was a significant increase in cardiac output in the oral treprostinil group compared to the placebo group (geometric mean 11.3% active vs. -6.4% placebo; ANCOVA p=0.005) and a corresponding significant reduction in pulmonary vascular resistance (PVR) (geometric mean -21.5 active vs. -1.8% placebo; ANCOVA p=0.02) from Baseline to Week 24. These data suggest that increased compliance contributes to the physiological mechanism by which oral treprostinil improves exercise capacity and delays clinical worsening for patients with PAH.

PULMONARY TO SYSTEMIC PULSATILE AND RESISTIVE VASCULAR RESPONSES TO EXERCISE IN PATIENTS WITH PULMONARY HYPERTENSION SECONDARY TO LEFT HEART DISEASE (HFPEF)

<h3>BACKGROUND</h3> Systemic and pulmonary arterial stiffening with age are said to be linked, and contribute towards the development of pulmonary hypertension (PH) with age. Systemic arterial stiffening may contribute to the development of PH due to left heart disease (PH-LHD). However, the relationships between the systemic and pulmonary circuit have not been as well described in populations with pulmonary hypertension. Exercise during right heart catheterization (RHC) is used to discriminate between PH-LHD and pulmonary arterial hypertension (PAH). In this study we aimed to describe the relationships between pulmonary and systemic compliance (a measure of vascular stiffening, also referred to as pulsatile loading) and vascular resistance (a measure of resistive loading) at rest and during exercise RHC, in patients with normal hemodynamics, PH-LHD and PAH. We hypothesized that systemic and pulmonary arterial stiffening would be linked in PH-LHD but not PAH. <h3>METHODS AND RESULTS</h3> A retrospective hemodynamic analysis was conducted using data from 80 individuals (50% female, 59±15 years) with dyspnea and/or suspected pulmonary hypertension who underwent RHC and a bout of semi-upright submaximal cycling. Exercise hemodynamic classifications were as follows: Normal – change in mean pulmonary artery pressure (mPAP) over cardiac output (CO)(ΔmPAP/ΔCO ≥3.2 woods units (WU)), Exercise PAH - ΔmPAP/ΔCO >3.2WU and exercise pulmonary arterial wedge pressure (PAWP) < 20mmHg, and Exercise PH-LHD - ΔmPAP/ΔCO >3.2WU and PAWP >20mmHg with exercise. Proportional relationships between pulsatile load in the pulmonary vs. systemic circuit are displayed in Table 1. There was a significantly greater increase in the pulmonary pulse pressure (PPP) to systemic pulse pressure (SPP) (73±40% to 93±51% vs. 51±29% to 63±36%, p < 0.001) and pulmonary vascular resistance (PVR) to systemic vascular resistance (SVR) (26±16% to 39±27% vs. 14±11% to 25±18%, p < 0.01) from rest to exercise in the PAH group when compared to PH-LHD. Otherwise, there were no differences in the total pulmonary resistance (TPulmR) to total peripheral resistance (TPR) ratio. There was a significant correlation between pulmonary (PulmCp) and systemic compliance (SysCp), both at rest (r2=0.33, p < 0.01) and during exercise (r2=0.16, p=0.05), in the PH-LHD group (Figure 1). <h3>CONCLUSION</h3> The proportional vascular loads between the pulmonary and systemic circulations differ as expected between PAH and PH-LHD. However, the net proportional resistive load (TPulmR/TPR) was very similar. There was a significant relationship between systemic and pulmonary stiffening (pulsatile load) at rest and exercise only in the PH-LHD group, which provides support for the hypothesis that systemic arterial stiffening is a mechanism that promotes the development of PH-LHD.

EXERCISE HEMODYNAMICS TO REVEAL LATENT PULMONARY VASCULAR ABNORMALITIES AMONG CHRONIC THROMBOEMBOLIC DISEASE PATIENTS

BACKGROUND Chronic thromboembolic pulmonary hypertension (CTEPH) is characterized by persistent and organized pulmonary thrombi and pulmonary hypertension (PH). Right heart catheterization (RHC) is the gold standard for diagnosis of PH, defined by a resting mean pulmonary artery pressure (mPAP) > 20 mmHg. Chronic organized thrombi, in the absence of PH at rest is termed chronic thromboembolic disease (CTED). Pulmonary endarterectomy (PEA) is indicated for CTEPH, however PEA is not routinely endorsed for CTED. Exercise is increasingly employed as a provocative maneuver during RHC to elicit abnormalities of pulmonary vascular and cardiac physiology in patients without PH at rest who are at risk of pulmonary vascular disease. Exercise RHC may expose abnormalities of pulsatile or resistive pulmonary vascular afterload in CTED patients and may potentially identify a subset of CTED patients who benefit from PEA surgery. We describe the proportion of CTED patients with latent pulmonary vascular hemodynamic abnormalities and their hemodynamic characteristics. METHODS AND RESULTS Consecutive patients with a resting mPAP ≤ 20 mmHg and CTED who completed an exercise hemodynamic study between November 2016 and September 2020 were included. We defined exercise abnormalities of pulmonary resistive load as mPAP/CO > 3 WU and exercise abnormalities of pulsatile load as the ratio of pulmonary pulse pressure to pulmonary artery wedge pressure (PP/PAWP) > 2.5. Thirty-seven CTED patients (32% female, 55±15 years) were analyzed. Resting hemodynamics for the entire cohort and exercise hemodynamics for patients with and without latent pulmonary vascular abnormalities are shown (Table 1). Twenty-two patients (59%) demonstrated latent pulmonary vascular abnormalities; 12 had an elevated pulsatile load (PP/PAWP 5.3±4.5), 5 had an elevated resistive load (mPAP/CO 3.7±0.7 WU) and 5 had both (mPAP/CO 3.7±0.5 WU, PP/PAWP 7.3±3.6). Patients with latent pulmonary vascular abnormalities exercised to lower work-rates (P=0.03) and had lower exercise PAWP (P=0.02). They were also characterized by higher pulmonary vascular resistance (P < 0.001) and impaired pulmonary artery compliance (P < 0.001) compared to patients without latent pulmonary vascular abnormalities. CONCLUSION Patients with CTED and resting mPAP ≤ 20mmHg, exercise demonstrated latent abnormal pulmonary vascular responses in over 50% of patients. These patients predominantly demonstrated abnormalities of pulsatile afterload relative to resistive afterload. Further study is required to understand if these patients benefit from PEA surgery. Chronic thromboembolic pulmonary hypertension (CTEPH) is characterized by persistent and organized pulmonary thrombi and pulmonary hypertension (PH). Right heart catheterization (RHC) is the gold standard for diagnosis of PH, defined by a resting mean pulmonary artery pressure (mPAP) > 20 mmHg. Chronic organized thrombi, in the absence of PH at rest is termed chronic thromboembolic disease (CTED). Pulmonary endarterectomy (PEA) is indicated for CTEPH, however PEA is not routinely endorsed for CTED. Exercise is increasingly employed as a provocative maneuver during RHC to elicit abnormalities of pulmonary vascular and cardiac physiology in patients without PH at rest who are at risk of pulmonary vascular disease. Exercise RHC may expose abnormalities of pulsatile or resistive pulmonary vascular afterload in CTED patients and may potentially identify a subset of CTED patients who benefit from PEA surgery. We describe the proportion of CTED patients with latent pulmonary vascular hemodynamic abnormalities and their hemodynamic characteristics. Consecutive patients with a resting mPAP ≤ 20 mmHg and CTED who completed an exercise hemodynamic study between November 2016 and September 2020 were included. We defined exercise abnormalities of pulmonary resistive load as mPAP/CO > 3 WU and exercise abnormalities of pulsatile load as the ratio of pulmonary pulse pressure to pulmonary artery wedge pressure (PP/PAWP) > 2.5. Thirty-seven CTED patients (32% female, 55±15 years) were analyzed. Resting hemodynamics for the entire cohort and exercise hemodynamics for patients with and without latent pulmonary vascular abnormalities are shown (Table 1). Twenty-two patients (59%) demonstrated latent pulmonary vascular abnormalities; 12 had an elevated pulsatile load (PP/PAWP 5.3±4.5), 5 had an elevated resistive load (mPAP/CO 3.7±0.7 WU) and 5 had both (mPAP/CO 3.7±0.5 WU, PP/PAWP 7.3±3.6). Patients with latent pulmonary vascular abnormalities exercised to lower work-rates (P=0.03) and had lower exercise PAWP (P=0.02). They were also characterized by higher pulmonary vascular resistance (P < 0.001) and impaired pulmonary artery compliance (P < 0.001) compared to patients without latent pulmonary vascular abnormalities. Patients with CTED and resting mPAP ≤ 20mmHg, exercise demonstrated latent abnormal pulmonary vascular responses in over 50% of patients. These patients predominantly demonstrated abnormalities of pulsatile afterload relative to resistive afterload. Further study is required to understand if these patients benefit from PEA surgery.

Left atrial conduit function modulates right ventricular afterload, exercise capacity and survival in heart failure patients.

To assess if left atrial phasic function characteristics modulate functional capacity/survival by impacting on the pulsatile component of right ventricular (RV) afterload, as represented by pulmonary arterial compliance (PAC). Sixty heart failure patients (67 ± 11 years, ejection fraction 39 ± 11%, range 20--62%) underwent 6 min walk test (6MWT) and 3D transthoracic echocardiography. Left atrial conduit was computed off-line, gathering simultaneous real-time 3D multibeats (six cycles) left atrial and left ventricular (LV) volume curves, with conduit (time) = [LV (time) - LV minimum volume] - [left atrial maximum volume - left atrial (time)], expressed as % LV stroke volume. Atrial stiffness (Kla) was computed using noninvasively assessed wedge pressure divided by left atrial reservoir (maximum - minimum) volume. PAC was obtained as ratio between RV stroke volume, obtained as pulsed Doppler RV outflow tract envelope∗cross-sectional area, and pulmonary pulse pressure, obtained by transforming tricuspid regurgitant velocity in millimetres of mercury and considering diastolic pulmonary as a fixed fraction of systolic pressure. Conduit averaged 34 ± 12%, PAC 3.1 ± 1.1 ml/mmHg, 6MWT 404 ± 154 m. Conduit was independent of LV volumes and ejection fraction, showing a direct dependence on noninvasive Kla (r = 0.56; P < 0.001). Dividing patients into tertiles according to 6MWT and to PAC, the largest conduit fraction was associated with the lowest functional capacity (P < 0.001) and most deranged PAC (P < 0.001), respectively, suggesting outmost RV haemodynamic burden. Tertiles of conduit predicted survival (P = 0.01). Conduit depends on noninvasively assessed Kla and appears to be increased in heart failure patients with lowest capacity and worst survival, likely as RV pulsatile afterload, as reflected by PAC, is highest in these individuals.

Respect The Notch: Under-appreciated Pulmonary Vascular Disease and Hemodynamic Collapse Post Left Ventricular Assist Device Placement

Introduction Right ventricular (RV) failure occurs in 15-20% of patients post Left ventricular Assist Device (LVAD) implantation and has been associated with increased mortality. Herein we describe a case of severe RV failure post LVAD implantation and how proper identification of the etiology led to a positive outcome. Case description A 58-year-old male with non-ischemic cardiomyopathy is admitted with decompensated heart failure. Right heart catheterization (RHC) showed right atrial pressure (RAP) 5 mmHg, Pulmonary artery pressure (PAP): 45/25, wedge pressure (PCWP) 24 mm Hg, pulmonary vascular resistance (PVR) of 1.4 woods units and cardiac index of 1.7 on inotropes. The patient underwent HMIII LVAD implantation. Immediately postop the patient developed shock. TTE showed an akinetic and dilated RV. He was placed on VA ECMO emergently and then transitioned to a percutaneous right ventricular assist device (RVAD). The patient eventually required dialysis. Decision-making Multiple mechanisms lead to RV failure after LVAD implantation. These include increased RV preload (from increased cardiac output and venous return or blood/fluid administration perioperatively), decreased contractility (LV decompression resulting in intraventricular septal left shift and decreased septal contribution to RV contractility), RV infarct, ventricular arrhythmias, and increased RV afterload (unmasking of pulmonary hypertension or pulmonary embolism). On review of the patient's echocardiogram post RVAD placement, there was RVAD flow dependent notching of the RV outflow tract (RVOT) pulse wave doppler (Figure 1A,B). RVOT notching is a validated sign of high PVR and prompted further review of patient's pre LVAD RHCs and TTEs. Excluding the RHC and TTE immediately pre LVAD implantation, prior RHCs showed RAP:PCWP ratio of 0.7, PAP of 70s/30s and PVR as high as 5.4 with concordant RVOT notching on TTE. The narrower pulmonary pulse pressure on the RHC immediately preceding LVAD implantation suggested a failing RV and was discordant with the lower RAP:PCWP (0.25) and lower PVR. Under-occlusion of the PCWP most likely led to a falsely elevated PCWP and falsely reduced PVR. With aggressive pulmonary vasodilator therapy, hemodynamics improved, the RVAD was explanted and dialysis was successfully discontinued. Figure 1C shows improvement of RVOT notching with this treatment. Conclusion Severe RV failure post LVAD implantation has a significant impact on morbidity/mortality. The echocardiogram provides valuable pathophysiological insights and is an important asset to interpreting invasive hemodynamics, especially pertaining to RV failure.

UNCOUPLING OF PULMONARY PULSE PRESSURE AND PULMONARY ARTERIAL WEDGE PRESSURE DURING EXERCISE IN DYSPNEIC PATIENTS WITH NORMAL RESTING HEMODYNAMICS

Hemodynamic response to exercise is used to evaluate causes of dyspnea in suspected pulmonary hypertension (PH) related to pulmonary vascular or left heart disease. Such studies may disclose abnormal increases in mean pulmonary artery pressure (mPAP) in the context of cardiac output, even when hemodynamics in the resting state are within normal limits. We hypothesized that the relationship between the pulmonary artery wedge pressure (PAWP) and the pulmonary pulse pressure (PP), closely coupled in health, may further discriminate specific abnormalities of this integrated physiology.

PULMONARY ARTERIAL CAPACITANCE AND RENAL FUNCTION IN PATIENTS WITH HEART FAILURE WITH PRESERVED AND REDUCED EJECTION FRACTION

Pulmonary arterial capacitance (PAC) defined by stroke volume divided by pulmonary pulse pressure, is a novel right heart catheterization (RHC) index, which has been shown to be associated with mortality and more cardiac events in heart failure. Given the strong association between heart failure,

Cardiovascular mechanics in the early stages of pulmonary hypertension: a computational study.

We formulate and study a new mathematical model of pulmonary hypertension. Based on principles of fluid and elastic dynamics, we introduce a model that quantifies the stiffening of pulmonary vasculature (arteries and arterioles) to reproduce the hemodynamics of the pulmonary system, including physiologically consistent dependence between compliance and resistance. This pulmonary model is embedded in a closed-loop network of the major vessels in the body, approximated as one-dimensional elastic tubes, and zero-dimensional models for the heart and other organs. Increasingly severe pulmonary hypertension is modeled in the context of two extreme scenarios: (1) no cardiac compensation and (2) compensation to achieve constant cardiac output. Simulations from the computational model are used to estimate cardiac workload, as well as pressure and flow traces at several locations. We also quantify the sensitivity of several diagnostic indicators to the progression of pulmonary arterial stiffening. Simulation results indicate that pulmonary pulse pressure, pulmonary vascular compliance, pulmonary RC time, luminal distensibility of the pulmonary artery, and pulmonary vascular impedance are much better suited to detect the early stages of pulmonary hypertension than mean pulmonary arterial pressure and pulmonary vascular resistance, which are conventionally employed as diagnostic indicators for this disease.

Longitudinal change in pulmonary arterial capacitance as an indicator of prognosis and response to therapy and in pulmonary arterial hypertension.

Pulmonary arterial hypertension (PAH) is a chronic progressive disease that leads to right heart failure and death. Pulmonary arterial capacitance (PAC), defined as stroke volume divided by the pulmonary pulse pressure, has been identified as a prognostic factor in PAH. The impact of changes in PAC over time, however, is unclear. We evaluated changes in PAC over time to determine if such changes predicted transplant-free survival. A single-center retrospective study of consecutive group 1 PAH patients who had two or more right heart catheterizations (RHC) between January 2007 and June 2016 was undertaken. Hemodynamic data, clinical data, and outcomes were collected. Univariate and multivariate Cox proportional-hazards modelling to identify the contribution of risk factors for a composite outcome of death or lung transplantation was done. Mixed-effects logistic regression was performed to investigate the association between the change in PAC value over time and the composite outcome. A P value < 0.05 was considered significant. In total, 109 consecutive patients with a total of 300 RHC data were identified. PAC correlated inversely with functional status (P < 0.001) and inversely with pulmonary vascular resistance (P < 0.001). PAC values increased with the addition of new PAH-specific medications. Mixed effects logistic regression modeling using longitudinal data showed that a decrease in PAC over the study period was associated with increased mortality and transplantation (adjusted P = 0.039) over the study period. Change in PAC was a better predictor of outcome over the study period than baseline PAC or changes in other hemodynamic or clinical parameters. Decreases in PAC were predictive of increased mortality or transplantation in patients with group 1 PAH. There was a trend towards increased PAC in response to the addition of a PAH-specific medication. Our data support the use of PAC as a therapeutic target in PAH.

Pulmonary Arterial Capacitance Index Is a Strong Predictor for Adverse Outcome in Children with Idiopathic and Heritable Pulmonary Arterial Hypertension

To evaluate the clinical utility of pulmonary artery capacitance index (PACi) in the assessment of disease severity and prognostic value in children with idiopathic and heritable pulmonary arterial hypertension (PAH). PACi is defined as the ratio of stroke volume index over pulmonary pulse pressure. A retrospective study was performed to compare PACi, brain natriuretic peptide (BNP), 6-minute walk distance, New York Heart association (NYHA) functional class, and adverse outcomes (hospitalization due to heart failure, lung transplantation, and cardiac mortality) in 72 Japanese children (10 ± 3.6 years) with idiopathic and heritable PAH. PACi had significant correlations with pulmonary vascular resistance index (r =-0.73, P < .0001), BNP levels (r = -0.40, P = .0008), and 6-minute walk distance (r = 0.57, P < .05). Statistically significant differences in PACi were observed between NYHA functional class II vs combined III and IV (median; 1.1 vs 0.6 mL/mm Hg/m2, respectively, P < .05). There were 25 of 72 (35%) children who had an adverse event including initiation of hospitalization due to heart failure, lung transplantation, and death. Cumulative event-free survival rate was significantly lower when PACi was <0.85 mL/mm Hg/m2 (log-rank test, P < .0001). PACi correlated with BNP and NYHA functional class and may serve as a strong prognostic marker in children with idiopathic and heritable PAH.

Pulmonary vascular capacitance as a predictor of vasoreactivity in idiopathic pulmonary arterial hypertension tested by adenosine

Background:Acute pulmonary vasoreactivity testing has been recommended in the diagnostic work-up of patients with idiopathic pulmonary arterial hypertension (IPAH). Pulmonary arteriolar capacitance (Cp) approximated by stroke volume divided by pulmonary pulse pressure (SV/PP) is considered as an independent predictor of mortality in patients with IPAH.Objectives:We sought to evaluate any differences in baseline and adenosine Cp between vasoreactive and non-vasoreactive IPAH patients tested with adenosine.Patients and Methods:Fourteen patients with IPAH and a vasoreactive adenosine vasoreactivity testing according to the ESC guidelines were compared with 24 IPAH patients with nonreactive adenosine test results.Results:There were no statistical significant differences between the two groups regarding NYHA class, body surface area, heart rate, and systemic blood pressure during right heart catheterization. Hemodynamic study showed no statistical significant differences in cardiac output/Index, mean pulmonary artery pressure, pulmonary vascular resistance, and baseline Cp between the two groups. There was a statistical significant but weak increase in adenosine Cp in vasoreactive group compared to non-reactive group (P = 0.04). Multivariable analysis showed an association between Cp and vasoreactivity (Beta = 2, P = 0.04, OR = 0.05 (95%CI = 0.003 - 0.9).Conclusions:Cp could be considered as an index for the prediction of vasoreactivity in patients with IPAH. Prediction of long-term response to calcium channel blockers in patients with IPAH and a positive vasoreactive test by this index should be addressed in further studies.

Intermittent positive pressure ventilation increases diastolic pulmonary arterial pressure in advanced COPD

ObjectivesTo measure the impact of intermittent positive pressure ventilation (IPPV) on diastolic pulmonary arterial pressure (dPAP) and pulmonary pulse pressure in patients with advanced COPD. BackgroundThe physiological effects of raised intrathoracic pressures upon the pulmonary circulation have not been fully established. Methods22 subjects with severe COPD receiving IPPV were prospectively assessed with pulmonary and radial arterial catheterization. Changes in dPAP were assessed from end-expiration to early inspiration during low and high tidal volume ventilation. ResultsInspiration during low tidal volume IPPV increased the median [IQR] dPAP by 3.9 [2.5–4.8] mm Hg (P < 0.001). During high tidal volume, similar changes were observed. The IPPV-associated change in dPAP was correlated with baseline measures of PaO2 (rho = 0.65, P = 0.005), pH (rho = 0.64, P = 0.006) and right atrial pressure (rho = −0.53, P = 0.011). ConclusionsIn severe COPD, IPPV increases dPAP and reduces pulmonary pulse pressure during inspiration.

PT372 Quantification of Intramyocardial Triglyceride by 1H-Magnetic Resonance Spectroscopy Using Fewer Number of Signal Averages Has High Feasibility, Excellent Agreement, and Significant Time Savings Compared to the “Gold Standard” Spectrum with 128 Signal Averages

Reliable markers of early disease are needed in pulmonary arterial hypertension (PAH). As measures of the contribution of abnormal vascular compliance to overall vascular resistance, resting and exercise pulmonary capacitance—defined as the stroke volume divided by the change in pulmonary pulse pressure—may be sensitive markers of early disease.We examined all patients in our pulmonary hypertension database with idiopathic PAH, who had undergone rest and exercise right heart catheterisation in one sitting. Standard haemodynamic measurements were obtained, including pulmonary capacitance. These results were compared to age- and sex-matched normal controls.We analysed 27 right heart catheterisations in idiopathic PAH patients and 23 in controls. Mean pulmonary artery pressure (MPAP), mean pulmonary capillary wedge pressure (mPCWP), pulmonary vascular resistance (PVR) and right ventricular stroke work index (RVSWI) were significantly higher at baseline in diseased patients, while Cardiac Index (CI) and pulmonary capacitance were significantly lower. MPAP, mPCWP, cardiac index and RVSWI increased significantly in both groups with exercise. Pulmonary capacitance decreased significantly in both groups. Pulmonary vascular resistance decreased with exercise in the control group only. Capacitance and PVR were inversely correlated at rest (time-constant of 0.79 s) and with exercise (time-constant of 0.56 s). The receiver operating characteristic (ROC) curve for capacitance as a diagnostic marker demonstrated an AUC of 0.96 at rest and 0.95 with exercise.In idiopathic pulmonary arterial hypertension (IPAH) there is a reduction in pulmonary capacitance at baseline and left-shift of the inverse capacitance-PVR relationship with exercise. Both resting and exercise pulmonary capacitance have potential as diagnostic markers in early disease.

Pulmonary Artery Dilatation Correlates With the Risk of Unexpected Death in Chronic Arterial or Thromboembolic Pulmonary Hypertension

Right ventricular failure does not explain all cases of death in patients with chronic pulmonary hypertension. Searching for alternative explanations, we evaluated the prognostic significance of main pulmonary artery (PA) dilatation in patients with pulmonary arterial hypertension (PAH) or chronic thromboembolic pulmonary hypertension (CTEPH). A retrospective outcome analysis was made of 264 patients (aged 46 ± 17 years; women, 69%; PAH, 82%) who underwent both CT scan measurement of the PA and right-sided heart catheterization (mean PA pressure, 57.6 ± 16.5 mm Hg) at initial evaluation. The diameter of the PA ranged from 28 to 120 mm (mean, 39 ± 8.6 mm; median, 38 mm) and was largest in patients with unrepaired congenital defects (42.6 ± 7.6 mm). Pulmonary pulse pressure (P = .04), lower age (P = .03), and duration of symptoms (P &lt; .001) were independently but weakly related to PA diameter. During follow-up (median, 38 months), 99 patients (37%) died. Of these 99 deaths, 73 (74%) were due to heart failure or comorbidities, and 26 (26%) were unexpected deaths (UE-Ds). PA diameter (hazard ratio [HR], 1.06 per 1 mm; 95% CI, 1.03-1.08), heart rate (HR, 1.30 per 10 beats/min; 95% CI, 1.01-1.66), and systolic pulmonary arterial pressure (HR, 1.02 per 1 mm Hg; 95% CI, 1.01-1.04) were the only independent predictors of UE-D and differed from the usual predictors found in the study group for all-cause mortality. PA diameter ≥ 48 mm had 95% specificity and 39% sensitivity and carried 7.5 times higher risk of UE-D (95% CI, 3.4-16.5; P &lt; .0001) during follow-up. PA dilatation emerges as an independent risk factor for death unexplained by right ventricular failure or comorbidities in patients with PAH and CTEPH. The possible mechanisms include, but are not limited to, PA compression of the left main coronary artery, PA rupture, or dissection with cardiac tamponade.

Prognostic Role of Pulmonary Arterial Capacitance in Advanced Heart Failure

Right ventricular (RV) dysfunction frequently occurs and independently prognosticates in left-sided heart failure. It is not clear which RV afterload measure has the greatest impact on RV function and prognosis. We examined the determinants, prognostic role, and response to treatment of pulmonary arterial capacitance (PAC, ratio of stroke volume over pulmonary pulse pressure), in relation to pulmonary vascular resistance (PVR) in heart failure. We reviewed 724 consecutive patients with heart failure who underwent right heart catheterization between 2000 and 2005. Changes in PAC were explored in an independent cohort of 75 subjects treated for acute decompensated heart failure. PAC showed a strong inverse relation with PVR (r=-0.64) and wedge pressure (r=-0.73), and provides stronger prediction of significant RV failure than PVR (area under the curve ROC 0.74 versus 0.67, respectively, P=0.003). During a mean follow-up of 3.2±2.2 years, both lower PAC (P<0.0001) and higher PVR (P<0.0001) portend more adverse clinical events (all-cause mortality and cardiac transplantation). In multivariate analysis, PAC (but not PVR) remains an independent predictor (Hazard ratio=0.92 [95% CI: 0.84-1.0, P=0.037]). Treatment of heart failure resulted in a decrease in PVR (270±165 to 211±88 dynes·s(-1)·cm(-5), P=0.002), a larger increase in PAC (1.65±0.64 to 2.61±1.42 mL/mm Hg, P<0.0001), leading to an increase in pulmonary arterial time constant (PVR×PAC) (0.29±0.12 to 0.37±0.15 second, P<0.0001). PAC bundles the effects of PVR and left-sided filling pressures on RV afterload, explaining its strong relation with RV dysfunction, poor long-term prognosis, and response to therapy.

Relationship of Pulmonary Arterial Capacitance and Mortality in Idiopathic Pulmonary Arterial Hypertension

The purpose of this study was to determine if pulmonary vascular capacitance predicts survival in patients with idiopathic pulmonary arterial hypertension (IPAH). The prognosis of patients with IPAH is difficult to predict, despite knowledge of clinical and hemodynamic parameters previously identified as predictors. We proposed a capacitance index of stroke volume divided by pulmonary pulse pressure (SV/PP) and prospectively gathered data on IPAH patients who underwent a right heart catheterization. SV/PP was analyzed as a predictor of mortality after adjusting for other modifiers of risk. During 4-year follow-up of 104 patients, 21 patients died. When compared with conventional markers, SV/PP was the strongest univariate predictor of mortality (hazard ratio 17.0 per ml.mm Hg(-1) decrease, 95% confidence interval 13.0 to 22.0; p < 0.0001). In successive bivariate analysis, SV/PP was the only predictor of mortality. In quartile analysis, the lowest SV/PP quartile had a 4-year mortality of 61%; the highest SV/PP had no deaths. The capacitance index (SV/PP) is a strong independent predictor of mortality in patients with IPAH.