High Pulmonary Artery Wedge Pressure Research Articles

The clinical and hemodynamic characteristics of pulmonary hypertension in patients with OSA-COPD overlap syndrome

BackgroundOur study aimed to assess the clinical and hemodynamic characteristics of pulmonary hypertension (PH) in patients with overlapping obstructive sleep apnea (OSA) and chronic obstructive pulmonary disease (COPD), referred to OSA-COPD overlap syndrome (OS). MethodsWe enrolled a total of 116 patients with OS, COPD, or OSA who underwent right heart catheterization (RHC) due to suspected PH. We conducted a retrospective analysis of the clinical and hemodynamic characteristics of these patients. ResultsAmong the three groups (OS group, n = 26; COPD group, n = 36; OSA group, n = 54), the prevalence of PH was higher in the OS group (n = 17, 65.4%)compared to OSA group (n = 26,48.1%) and COPD group (n = 20,55.6 %). Among three groups with PH, the superior vena cava pressure (CVP) and right ventricular pressure (RAP) were higher in the OS group than in the OSA group (P < 0.05). Patients in the OS and COPD groups had higher pulmonary artery wedge pressure (PAWP) than in the OSA group (14.88 ± 4.79 mmHg, 13.45 ± 3.68 mmHg vs. 11.00 ± 3.51 mmHg, respectively, P < 0.05). OS patients with PH exhibited higher respiratory event index (REI), time spent with SpO2 <90%, oxygen desaturation index (ODI), minimal SpO2 (MinSpO2) and mean SpO2 (MSpO2) compared to OS patients without PH. After adjusting for potential covariates, we found that MinSpO2 (OR 0.937, 95 % CI 0.882–0.994, P = 0.032), MSpO2 (OR 0.805, 95% CI 0.682–0.949, P = 0.010), time spent with SpO2 <90% (OR 1.422, 95% CI 1.137–1.780, P = 0.002), and FEV1 % pred (OR 0.977, 95 % CI 0.962–0.993, P = 0.005) were related to the development of PH. ConclusionsPatients with OS showed higher prevalence of PH, along with higher PAWP, CVP and RAP. Worse nocturnal hypoxemia was found in OS patients with PH.

Long Term Survival of Heritable Pulmonary Arterial Hypertension Associated with Hereditary Hemorrhagic Telangiectasia: A Case Series.

Hereditary hemorrhagic telangiectasia (HHT) is a hereditary disease characterized by recurrent epistaxis, mucocutaneous telangiectasias, and visceral arteriovenous malformations. Multiple genetic mutations have been linked to this rare disease, including ENG, ALK1 (ACVRL1), and MADH4. Pulmonary hypertension is a potential complication of HHT, with the most common phenotypes being World Health Organization (WHO) group 1 heritable pulmonary arterial hypertension (PAH), which is typically associated with ALK1 mutation; WHO group 2 pulmonary hypertension due to high output heart failure from hepatic arteriovenous malformations and/or anemia; and WHO group 2 due to high pulmonary artery wedge pressure. There is scarce evidence to help guide treatment of heritable PAH in HHT, and observational literature suggests that patients with HHT and heritable PAH have a worse prognosis compared to patients with idiopathic PAH. We describe the diagnosis, pulmonary hemodynamics, and detailed treatment courses of three patients with ALK1-associated HHT and PAH, who all exhibited objective clinical improvement with parenteral prostacyclins and oral agents.

Impact of severe secondary tricuspid regurgitation on rest and exercise hemodynamics of patients with heart failure and a preserved left ventricular ejection fraction.

Both secondary tricuspid regurgitation (STR) and heart failure with preserved ejection fraction (HFpEF) are relevant public health problems in the elderly population, presenting with potential overlaps and sharing similar risk factors. However, the impact of severe STR on hemodynamics and cardiorespiratory adaptation to exercise in HFpEF remains to be clarified. To explore the impact of STR on exercise hemodynamics and cardiorespiratory adaptation in HFpEF. We analyzed invasive hemodynamics and gas-exchange data obtained at rest and during exercise from HFpEF patients with severe STR (HFpEF-STR), compared with 1:1 age-, sex-, and body mass index (BMI)- matched HFpEF patients with mild or no STR (HFpEF-controls). Twelve HFpEF with atrial-STR (mean age 72 years, 92% females, BMI 28 Kg/m2) and 12 HFpEF-controls patients were analyzed. HFpEF-STR had higher (p < 0.01) right atrial pressure than HFpEF-controls both at rest (10 ± 1 vs. 5 ± 1 mmHg) and during exercise (23 ± 2 vs. 14 ± 2 mmHg). Despite higher pulmonary artery wedge pressure (PAWP) at rest in HFpEF-STR than in HFpEF-controls (17 ± 2 vs. 11 ± 2, p = 0.04), PAWP at peak exercise was no more different (28 ± 2 vs. 29 ± 2). Left ventricular transmural pressure and cardiac output (CO) increased less in HFpEF-STR than in HFpEF-controls (interaction p-value < 0.05). This latter was due to lower stroke volume (SV) values both at rest (48 ± 9 vs. 77 ± 9 mL, p < 0.05) and at peak exercise (54 ± 10 vs. 93 ± 10 mL, p < 0.05). Despite these differences, the two groups of patients laid on the same oxygen consumption isophlets because of the increased peripheral oxygen extraction in HFpEF-STR (p < 0.01). We found an inverse relationship between pulmonary vascular resistance and SV, both at rest and at peak exercise (R 2 = 0.12 and 0.19, respectively). Severe STR complicating HFpEF impairs SV and CO reserve, leading to pulmonary vascular de-recruitment and relative left heart underfilling, undermining the typical HFpEF pathophysiology.

Dynamic chest radiography as a novel minimally invasive hemodynamic imaging method in patients with heart failure

PurposeDynamic chest radiography allows for non-invasive cardiopulmonary blood flow assessment. However, data on its use for heart failure hemodynamic assessment are scarce. We utilized dynamic chest radiography to estimate heart failure hemodynamics. MethodTwenty heart failure patients (median age, 67 years; 17 men) underwent dynamic chest radiography and right heart catheterization. The analyzed images were 16-bit images (grayscale range: 0–65,535). Right atrial, right pulmonary artery, and left ventricular apex pixel values (average of the grayscale values of all pixels within a region of interest) were measured. The correlations of the minimum, maximum, mean, amount of change, and rate of change in pixel values with right atrial pressure, pulmonary artery pressure, pulmonary artery wedge pressure, and cardiac index were analyzed. ResultsThe mean right atrial pixel value and mean right atrial pressure (R = −0.576, P = 0.008), mean right pulmonary artery pixel value and mean pulmonary artery pressure (R = −0.546, P = 0.013), and left ventricular apex pixel value change rate and mean pulmonary artery wedge pressure (R = −0.664, P = 0.001) or cardiac index (R = 0.606, P = 0.005) were correlated. The left ventricular apex pixel value change rate identified low cardiac index (area under the curve, 0.792; 95% confidence interval, 0.590–0.993; P = 0.031) and low cardiac index with high pulmonary artery wedge pressure (area under the curve, 0.902; 95% confidence interval, 0.000–1.000; P = 0.030). ConclusionsDynamic chest radiography is a minimally invasive tool for heart failure hemodynamic assessment.

Quantitative estimation of pulmonary artery wedge pressure from chest radiographs by a regression convolutional neural network

Abstract Introduction Recent studies reported that a convolutional neural network (CNN; a deep learning model) can detect elevated pulmonary artery wedge pressure (PAWP) from chest radiographs, the diagnostic images most commonly used for assessing pulmonary congestion in heart failure. However, no method has been published for quantitatively estimating PAWP from such radiographs. We hypothesized that a regression CNN, an alternative type of deep learning, could be a useful tool for quantitatively estimating PAWP from chest radiographs in cardiovascular diseases. Methods We retrospectively enrolled 936 patients with cardiovascular diseases who had undergone right heart catheterization (RHC) and chest radiography and estimated PAWP by constructing a regression CNN based on the VGG16 model. We randomly categorized 80% of the data as training data (training group, n=748) and 20% as test data (test group, n=188). Moreover, we tuned the learning rate–one of the model parameters–by 5-hold cross-validation of the training group. Correlations between PAWP measured by RHC (ground truth [GT] PAWP) and PAWP derived from the regression CNN (estimated PAWP) were tested. To visualize how the regression CNN assessed the images, we created a regression activation map (RAM), a visualization technique for regression CNN. Results Estimated PAWP correlated significantly with GT PAWP in both the training (r=0.76, P&amp;lt;0.001) and test group (r=0.62, P&amp;lt;0.001). Bland-Altman plots found a mean (SEM) difference between GT and estimated PAWP of −0.23 (0.16) mm Hg in the training and −0.05 (0.41) mm Hg in the test group. The RAM showed that our regression CNN model estimated high PAWP by focusing on the cardiomegaly and pulmonary congestion. In the test group, the area under the curve (AUC) for detecting elevated PAWP (≥18 mm Hg) produced by the regression CNN model was similar to the AUC of an experienced cardiologist (0.86 vs 0.83, respectively; P=0.24). Conclusion This proof-of-concept study shows that regression CNN can quantitatively estimate PAWP from standard chest radiographs in cardiovascular diseases. Funding Acknowledgement Type of funding sources: Private company. Main funding source(s): The Bayer Academic Support

Quantitative estimation of pulmonary artery wedge pressure from chest radiographs by a regression convolutional neural network

Recent studies reported that a convolutional neural network (CNN; a deep learning model) can detect elevated pulmonary artery wedge pressure (PAWP) from chest radiographs, the diagnostic images most commonly used for assessing pulmonary congestion in heart failure. However, no method has been published for quantitatively estimating PAWP from such radiographs. We hypothesized that a regression CNN, an alternative type of deep learning, could be a useful tool for quantitatively estimating PAWP in cardiovascular diseases. We retrospectively enrolled 936 patients with cardiovascular diseases who had undergone right heart catheterization (RHC) and chest radiography and estimated PAWP by constructing a regression CNN based on the VGG16 model. We randomly categorized 80% of the data as training data (training group, n = 748) and 20% as test data (test group, n = 188). Moreover, we tuned the learning rate—one of the model parameters—by 5-hold cross-validation of the training group. Correlations between PAWP measured by RHC [ground truth (GT) PAWP] and PAWP derived from the regression CNN (estimated PAWP) were tested. To visualize how the regression CNN assessed the images, we created a regression activation map (RAM), a visualization technique for regression CNN. Estimated PAWP correlated significantly with GT PAWP in both the training (r = 0.76, P < 0.001) and test group (r = 0.62, P < 0.001). Bland–Altman plots found a mean (SEM) difference between GT and estimated PAWP of − 0.23 (0.16) mm Hg in the training and − 0.05 (0.41) mm Hg in the test group. The RAM showed that our regression CNN model estimated high PAWP by focusing on the cardiomegaly and pulmonary congestion. In the test group, the area under the curve (AUC) for detecting elevated PAWP (≥ 18 mm Hg) produced by the regression CNN model was similar to the AUC of an experienced cardiologist (0.86 vs 0.83, respectively; P = 0.24). This proof-of-concept study shows that regression CNN can quantitatively estimate PAWP from standard chest radiographs in cardiovascular diseases.

Hemodynamic assessment and risk classification for successful weaning of Impella in patients with cardiogenic shock.

Clinical predictors for successful weaning of patients from Impella heart pump have not been clarified. We aimed to elucidate the relationship between pulmonary artery catheter (PAC) parameters at the time of Impella weaning and subsequent outcomes. We enrolled consecutive patients who had received Impella for cardiogenic shock. PAC data were collected immediately before Impella weaning. Patients were classified as non-survivors if they died or required any mechanical circulatory support reintroduction within 30days of weaning. Of 81 patients enrolled, 61 underwent Impella weaning. Of these, 16 were non-survivors. Predictive indicators of non-survival were high pulmonary artery wedge pressure (PAWP; hazard ratio [HR] per 5mmHg 1.97, 95% CI 1.35-2.80; p<0.001), high mean pulmonary artery pressure (MPAP; HR per 5mmHg 1.90, 1.38-2.58; p<0.001), and low cardiac power output (CPO; HR per 0.1 Watts 0.71, 0.52-0.92; p=0.006). Cutoff values of PAWP 20mmHg, MPAP 22mmHg, and CPO 0.59 Watts showed strong associations with 30-day non-survival risk (low risk 8% in patients with low PAWP and high CPO or 4% in patients with low MPAP and high CPO; high risk 100% in patients with high PAWP and low CPO or 82% in patients with high MPAP and low CPO). PAWP or MPAP higher than the cutoff with CPO below the cutoff at Impella weaning were associated with worse outcomes. We proposed a risk classification model for successful Impella weaning using PAC.

High prevalence of occult left ventricular diastolic dysfunction detected by exercise stress test in systemic sclerosis

Despite the poor prognosis of systemic sclerosis (SSc) due to the co-occurrence of left ventricular diastolic dysfunction (LVDD), presence of occult LVDD has not been sufficiently investigated. This retrospective study aimed to reveal the prevalence and determinants of occult LVDD in patients with SSc by exercise stress test. Forty-five SSc patients (age, 63 ± 13 years; men/women, 6/39) with normal pulmonary artery pressure and pulmonary artery wedge pressure (PAWP) at rest underwent a symptom-limited exercise test with right heart catheterization using a supine cycle ergometer; haemodynamic parameters at rest, leg raise and during exercise were evaluated. Occult LVDD defined PAWP ≥ 25 mmHg during exercise was seen in 13 patients (29%). Higher PAWP, lower pulmonary vascular resistance and diastolic pulmonary pressure gradient, larger left atrium at rest, and higher PAWP during leg raise (15 ± 4 vs 10 ± 4 mmHg in non-LVDD group, p < 0.001) were observed in the occult LVDD group. The area under the ROC curve for PAWP after leg raise was largest at 0.83 (95% CI: 0.70–0.95, p = 0.001). About one-third (29%) of SSc patients with normal haemodynamics at rest showed occult LVDD. A higher PAWP after leg raise could be useful for detecting occult LVDD.

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

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

Right ventricular hemodynamics and performance in relation to perfusion during first year after heart transplantation.

AimsWe aim to evaluate changes in invasive haemodynamics, right ventricular (RV) function, and perfusion during the first year after heart transplantation (HTx) and to determine the relation between RV function and myocardial perfusion.Methods and resultsThirty patients were prospectively enrolled at the time of HTx. Right heart catheterization (RHC), comprehensive 2D and 3D echocardiography and cardiac biomarkers were performed at baseline (≤2 weeks after HTx) and at follow‐up 1, 3, 6, and 12 months after HTx. At 12 months, HTx patients were subjected to an exercise stress test with assessment of maximal oxygen consumption (VO2max). RV myocardial perfusion reserve was evaluated by 15O‐H2O positron emission tomography at baseline and at 3 and 12 months after HTx. A group of 43 healthy subjects served as echocardiographic controls and a subgroup comprising 16 healthy controls underwent exercise stress test with simultaneous RHC. At baseline, HTx patients had higher pulmonary artery wedge pressure (PAWP) and right atrial pressure (RAP) and pulmonary vascular resistance (PVR) than healthy controls whereas cardiac index (CI) was reduced (PAWP; 14 mmHg [8;17] vs. 8 mmHg [7;10]; RAP: 7 mmHg [4;11] vs. 5 mmHg [4;6]; PVR: 1.9 wood units [1.3;2.6] vs. 1.1 wood units [1.0;1.4]; CI 2.4 L/min/m2 [2.2;2.8] vs. 3.3 L/min/m2 [2.8;.3.6], all P < 0.05). Normalization of filling pressures and CI was seen 3–6 months after HTx. During follow‐up, RV function in terms of 3D ejection fraction (EF) and longitudinal strain (LS) improved in HTx patients but remained reduced compared with healthy controls at 12 months follow‐up (3D RV EF: 52 ± 7% vs. 60 ± 8%; RV LS: 22 ± 4% vs. 28 ± 5%, both P < 0.001). During follow‐up, RV perfusion reserve improved (baseline 2.1 ± 0.9; 3 months follow‐up 3.2 ± 0.8; 12 months follow‐up 3.7 ± 1.1, P < 0.0001). RV perfusion reserve significantly correlated to cardiac markers in terms of troponin T (r = −0.62, P < 0.0001), NT‐proBNP (r = −0.65, P < 0.0001), RAP (r = −0.43, P < 0.01) and CI (r = 0.37, P < 0.01) and with VO2max 12 months after HTx (r = 0.75, P < 0.01).ConclusionsNormalization of left and right atrial filling pressures is demonstrated within the first 3 to 6 months after HTx. RV function and RV perfusion reserve correlated and gradually improved during the first year after HTx but RV function remained reduced in HTx patients compared with healthy controls.

The isobaric pulmonary arterial compliance in pulmonary hypertension.

Pulmonary hypertension is associated with stiffening of pulmonary arteries which increases right ventricular pulsatile loading. High pulmonary artery wedge pressure (PAWP) in postcapillary pulmonary hypertension (Pc-PH) further decreases pulmonary arterial compliance (PAC) at a given pulmonary vascular resistance (PVR) compared with precapillary pulmonary hypertension, thus responsible for a higher total arterial load. In all other vascular beds, arterial compliance is considered as mainly determined by the distending pressure, due to non-linear stress-strain behaviour of arteries. We tested the applicability, advantages and drawbacks of two comparison methods of PAC depending on the level of mean pulmonary arterial pressure (mPAP; isobaric PAC) or PVR.Right heart catheterisation data including PAC (stroke volume/pulse pressure) were obtained in 112 Pc-PH (of whom 61 had combined postcapillary and precapillary pulmonary hypertension) and 719 idiopathic pulmonary arterial hypertension (iPAH).PAC could be compared over the same mPAP range (25–66 mmHg) in 792 (95.3%) out of 831 patients and over the same PVR range (3–10.7 WU) in only 520 (62.6%) out of 831 patients. The main assumption underlying comparisons at a given PVR was not verified as the PVR×PAC product (RC-time) was not constant but on the contrary more variable than mPAP. In the 788/831 (94.8%) patients studied over the same PAC range (0.62–6.5 mL·mmHg−1), PVR and thus total arterial load tended to be higher in iPAH.Our study favours comparing PAC at fixed mPAP level (isobaric PAC) rather than at fixed PVR. A reappraisal of the effects of PAWP on the pulsatile and total arterial load put on the right heart is needed, and this point deserves further studies.

Left ventricular filling pressure in Tetralogy of Fallot: Correlation between invasive and noninvasive indices

BackgroundLeft heart filling pressures, as measured by pulmonary artery wedge pressure (PAWP), is associated with heart failure related mortality. Because of the prognostic importance of PAWP, several echocardiographic indices have been proposed for noninvasive assessment of PAWP. However, these indices have not been validated in the congenital heart disease population. The purpose of this study was to determine the correlation between echocardiographic indices of PAWP, and the effect of high PAWP on transplant-free survival in adults with tetralogy of Fallot (TOF). MethodsRetrospective study of adult TOF patients that underwent cardiac catheterization at Mayo Clinic, 1990–2017. We selected these pre-defined set of echocardiographic indices of LV diastolic function: mitral valve early velocity (E), mitral valve early and late velocity ratio (E/A), mitral valve deceleration time (DT), mitral annular tissue Doppler early velocity (e′), and left atrial volume index (LAVI). ResultsOf the echocardiographic indices analyzed among 213 patients (age 37 ± 14 years), only E velocity (β = 5.83, standard error = 1.52, p < 0.001) and LAVI (β = 0.14, standard error = 0.05, p = 0.007) correlated with PAWP. LAVI > 28 ml/m2 had sensitivity of 79% and specificity of 63% (AUC 0.712), and E velocity > 1.0 m/s had sensitivity of 66% and specificity of 89% (AUC 0.692), for detecting PAWP > 15 mmHg. LAVI > 28 ml/m2 was associated with reduced 10-year transplant-free survival (49% vs 90%, p < 0.001). ConclusionThis study supports the use of LAVI for noninvasive assessment of PAWP and for prognostication. Further studies are required to validate these results in a different population.

Determinants and Prognostic Implications of Left-Heart Filling Pressures in Tetralogy of Fallot

BackgroundElevated pulmonary artery wedge pressure (PAWP) is the hallmark of left-heart failure and is responsible for heart failure symptoms and mortality. Although PAWP typically correlates with right atrial pressure (RAP), it is primarily dependent on left-heart myocardial properties and volume status. As right-heart disease can occur in the absence of left-heart disease in patients with tetralogy of Fallot (TOF), we hypothesized that RAP was the primary determinant of PAWP in this population. MethodsA cohort study of adults with TOF that underwent right-heart catheterization at Mayo Clinic Rochester (1990 to 2017) to determine the relationship among RAP, PAWP, and mortality. ResultsAmong 213 patients (male 105; age 37 ± 14 years), the mean PAWP was 14 ± 5 mm Hg, and RAP was 11 ± 5 mm Hg. RAP was the strongest predictor of PAWP (β = 0.68, standard error = 0.06, P < 0.001), independent of left-heart disease and atherosclerotic cardiovascular risk factors. The patients with high PAWP also had normal tissue Doppler velocities, suggesting normal left-ventricular myocardial properties. PAWP was an independent predictor of death/transplant (hazard ration [HR] 1.11, 95% confidence interval [CI], 1.03-1.20, P = 0.004). However, when RAP was incorporated into the regression model, RAP (and not PAWP) became the independent predictor of outcomes (HR 1.14, 95% CI, 1.06-1.22, P = 0.001). ConclusionsThe current study showed that RAP was the primary determinant of PAWP and accounts, to some extent, for the mortality in patients with TOF and high PAWP. The data provide new insight in the pathophysiology of disease progression for symptomatic patients with TOF.

P4690Effects of pulmonary artery wedge pressure on right ventricular pulsatile loading in pulmonary hypertension: a reappraisal based on pulmonary arterial isobaric stiffness

Abstract Background Pulmonary hypertension (PH) is associated with stiffening of pulmonary arteries. Previous studies have suggested that high pulmonary artery wedge pressure (PAWP) in postcapillary PH (Pc-PH) further augments PA stiffness at a given level of pulmonary vascular resistance as compared to pulmonary arterial hypertension (PAH). However, these studies do not take into account differences in distending pressure (mean PA pressure, mPAP), which has an effect on stiffness due to non-linear stress-strain behavior of arteries. Purpose To compare total PA stiffness between Pc-PH and idiopathic PAH (iPAH) studied at similar mPAP (isobaric stiffness). Methods This was an analysis of right heart catheterization results obtained in 112 Pc-PH and 112 iPAH patients extracted from the French PAH network registry and matched for mPAP (median 38 vs 39 mmHg, P=NS), age (70.5 years each) and sex (64% female each). Total PA stiffness was calculated as the ratio of PA pulse pressure to indexed stroke volume. Results Total PA stiffness (n=224) increased with mPAP (Spearman's rho = 0.66) and decreased with PAWP (rho = - 0.17) (each P&lt;0.01). The isobaric stiffness was lower in Pc-PH (median (IQR) = 0.91 (0.64–1.39) mmHg/mL/m2) than in iPAH (1.18 (0.83–1.62) mmHg/mL/m2, P&lt;0.01). The patients were then stratified according to their mPAP (25–35 mmHg, n=74 (37/37); 36–43 mmHg, n=75 (34/41); and 44–66 mmHg, n=75 (41/34)). The isobaric stiffness was lower in Pc-PH than iPAH in the 1st mPAP tertile (0.62 vs 0.83 mmHg/mL/m2, P=0.06), in the 2nd mPAP tertile (0.76 vs 1.22 mmHg/mL/m2, P&lt;0.01) and in the 3rd mPAP tertile (1.41 vs 1.77 mmHg/mL/m2, P&lt;0.01). The pulmonary vascular resistance was lower in Pc-PH than iPAH in every mPAP tertile (each P&lt;0.01). Finally, Pc-PH had a higher indexed stroke volume than iPAH (37 (29–48) vs 32 (27–40) mL/m2, P&lt;0.01) while systolic PA pressure and PA pulse pressure were similar. Conclusion Unexpectedly, the isobaric pulmonary arterial stiffness was lower in Pc-PH than iPAH patients. It is proposed that PAWP attenuates the increase in RV pulsatile loading in PH when the natural high-strain-induced stiffening was accounted for. This may contribute to a less impaired right ventricular-PA coupling leading to higher indexed stroke volume in Pc-PH than iPAH despite similar PA pressure. At every mPAP level, both the lower PA stiffness and lower pulmonary vascular resistance in Pc-PH than in iPAH may contribute to explain differences in the pressure overload-induced right ventricular adaptation between the two diseased groups, a point that deserves to be confirmed by further studies. Acknowledgement/Funding University regular funds

Relation of Lymphangiogenic Factor Vascular Endothelial Growth Factor-D to Elevated Pulmonary Artery Wedge Pressure

Lymphatic flow is augmented in states of chronic heart failure (cHF). However, the biological mechanism driving increased lymphatic flow capacity (lymphangiogenesis) in cHF is unknown. Recent studies have indicated that vascular endothelial growth factors (VEGF-A, -C, and -D) are involved in lymphangiogenesis. This study examined the association between VEGF-A, -C, and -D levels, invasively measured hemodynamics, and heart failure symptoms. Subjects who underwent clinically indicated right heart catheterization at Medical University of South Carolina between 12/2016 and 7/2018 were eligible for inclusion. These subjects underwent clinical assessment of cHF severity (including 6MWT and KCCQ), hemodynamic assessment with right heart catheterization, laboratory studies including B-type natriuretic peptide, and concomitant measurement of VEGF-A, -C, and -D. Fifty-six patients were included for analysis. Subjects with elevated pulmonary artery wedge pressure (PAWP) had significantly higher VEGF-D levels (263 ± 415 pg/ml vs 65 ± 101 pg/ml; p = 0.02). PAWP was not associated with VEGF-A or VEGF-C levels. When stratified by VEGF-D, subjects with elevated VEGF-D had clinical and hemodynamic characteristics associated with worse HF severity (lower ejection fraction, higher b-type natriuretic peptide, higher PAWP, lower cardiac output), but were not more symptomatic by Kansas City Cardiomyopathy Questionnaire scores and had similar 6-minute walk test distance compared with subjects with lower VEGF-D. Subjects with an elevated VEGF-D were more likely to have a diagnosis of heart failure for >3 years. In conclusion, VEGF-D is associated with elevated PAWP in cHF, and elevated VEGF-D may mitigate cHF symptoms.

Serum Chloride Levels Track With Survival in Patients With Pulmonary Arterial Hypertension

Serum chloride is an important homeostatic biomarker in left heart failure, with significant prognostic implications. The impact of serum chloride in the long-term survival of patients with pulmonary arterial hypertension (PAH) is unknown. We tested whether serum chloride levels are associated with long-term survival in patients with PAH. We included patients with idiopathic or heritable PAH who had a basic metabolic panel performed at the time of their diagnostic right heart catheterization. Laboratory results were recorded both at diagnosis and 6-month follow-up. We included 277 patients, mean age 51 ± 18 years and 73%women, of whom 254 had a follow-up electrolyte determination at 6months. Serum chloride was 102.9 ± 3.9mM/L at diagnosis. A serum chloride≤ 100mM/L was noted in 65 (24%) and 53 (21%) patients at diagnosis and 6months, respectively. Patients with serum chloride≤ 100mM/L at 6months tracked with increase mortality when adjusted by age, sex, pulmonary vascular resistance, diuretics or prostacyclin analogs usage, and serum creatinine and sodium at 6months (hazard ratio, 1.83; 95%CI, 1.11-3.00). This group of patients was older, with decreased functional capacity, had worse renal function, took more diuretics, had higher pulmonary artery wedge pressure but lower mean pulmonary artery pressure, transpulmonary gradient, and pulmonary vascular resistance. Serum chloride at 6months from the PAH diagnosis is a strong and independent predictor of mortality in patients with idiopathic or heritable PAH, even after adjusting serum sodium, renal function, diuretic, and prostacyclin analog usage.

The importance of blood pressure response to Valsalva maneuver in patients with puhnonary hypertension

Objective To use a simple bedside technique to verify the pathophysiological mechanism of pulmonary hypertension （PH） in different races. Method The Valsalva maneuver （VM） was performed in patients referred to a specialty PH clinic. The blood pressure response of patients to VM was in different fashions. The blood pressure （BP） was measured by using cuff and stethoscope. When the cuff was inflated to 15 mmHg above the systolic pressure, sound could be heard by auscultation during VM and when the cuff was deflated the sound disappeared over 3 heart beats which was considered as abnormal BP response, and less than 3 heart beats defined as normal BP response. The right heart catheterization in patients with PH as a part of the standard evaluation. Results This study included 84 patients with a mean age of （63 ± 16） years. Those with abnormal BP response to VM had higher pulmonary artery wedge pressure （PAWP） [（22.5±6.6） vs. （11.9±4.3） mmHg, P 〈0.0001] and lower pulmonary vascular resistance [（5.8 ± 4.0） vs. （8.1 ± 4.6 ） WU, P = 0.01]. Blood pressure response to VM did not correlate with mean pulmonary artery （PA） pressure [（46.2 ± 9.9） vs. （43.4 ±10.4） mmHg, P =0.20] or cardiac index （both 2.4 ± 0.6 L/min/m^2）. The abnormal BP response to VM had high sensitivity （89.4%）, specificity （86.1%） and accuracy （86.9%） for determining PAWP〉 15 mmHg.Conclusions BP response to Valsalva maneuver provides important information about left heart filling pressures in patients with PH. Key words: Pulmonary hypertension; Hemodynamics; Valsalva maneuver

Acute Hemodynamic Effects of Intravenous Sildenafil Citrate in Congestive Heart Failure: Comparison of Phosphodiesterase Type-3 and -5 Inhibition

The reversibility of elevated pulmonary vascular resistance in heart failure bears an important relation to outcome after cardiac transplantation. The phosphodiesterase 3 (PDE3) and PDE5 inhibitors both increase levels of cyclic nucleotides in the vascular smooth muscle, causing vasodilatation. PDE3 inhibitors also have direct inotropic effects. We contrasted the acute hemodynamic responses to intravenous PDE3 and PDE5 inhibitors in patients with congestive cardiac failure to assess their relative suitability for reversibility testing in this setting. Thirty patients undergoing assessment for cardiac transplantation underwent right heart catheterization. Patients were randomized to receive an intravenous bolus of milrinone (0.05 mg/kg) or sildenafil citrate at a high (0.43 mg/kg) or low dose (0.05 mg/kg). Differences between low- and high-dose sildenafil were not significant. Both agents caused similar reductions in systemic and pulmonary vascular resistance. Milrinone caused significantly greater reductions in pulmonary artery wedge and mean pulmonary artery pressure, and increases in heart rate. In all study groups, greater increases in cardiac index (>25%) were seen in patients with a higher pulmonary artery wedge pressure at baseline (29 +/- 1 vs 20 +/- 2 mm Hg; p < 0.001). In end-stage congestive cardiac failure, intravenous milrinone and sildenafil both cause similar reductions in systemic and pulmonary vascular resistance; however, milrinone has more cardiac selective effects on left ventricular filling and heart rate. Both agents appear to have a suitable hemodynamic profile for testing of reversibility of secondary pulmonary hypertension in congestive cardiac failure. Larger studies are needed to confirm these results.

Usefulness of the Pulmonary Arterial Systolic Pressure to Predict Pulmonary Arterial Wedge Pressure in Patients With Normal Left Ventricular Systolic Function

Tissue Doppler imaging combined with transmitral Doppler permits estimation of pulmonary artery wedge pressure (PAWP) in many, but not all, patients, whereas pulmonary artery systolic pressure (PASP) and cardiac output (time-velocity integral method) are routinely measured. It was hypothesized that simple Doppler echocardiographic measurements could be used to estimate PAWP in many patients by rearranging the equation for pulmonary vascular resistance ([mean pulmonary artery pressure - (left atrial pressure/cardiac output)] x 80). Data from 69 patients (mean age 59 +/- 15 years) were reviewed, including cardiac output, transmitral mitral E wave velocity, and lateral tissue Doppler imaging mitral annular early diastolic velocity. PAWP was determined in the 2 ways of (1) measured (PAWPm) using the regression equation PAWPm = 1.91 + (1.24 * transmitral mitral E wave velocity/mitral annular early diastolic velocity) developed and validated by Nagueh, and (2) using a nomogram that we developed to predict PAWP when cardiac output and PASP were known. Moderately strong correlation was found between PASP and PAWPm (r = 0.73), and this correlation improved when excluding patients with pulmonary or liver disease and restricting cardiac output to 3.5 to 6.0 L/min (physiologic range; r = 0.81). Furthermore, the relation between PAWPm and PASP allowed for discrimination of high versus low PAWP: 36 of 37 patients with PASP < or =30 mm Hg had PAWPm < or =15 mm Hg (sensitivity 97%, specificity 47%). Conversely, 9 of 9 patients with PASP > or =40 mm Hg had PAWPm > or =12 mm Hg (sensitivity 100%, specificity 70%). Predicted PAWP correlated well with PAWPm (r = 0.63) and improved when patients with liver or pulmonary disease were excluded (r = 0.83). In conclusion, PASP strongly correlated with PAWP, and this principle can be exploited to rapidly detect patients with low or high PAWP.

Changes in Plasma N-Terminal proBNP Levels and Ventricular Filling Pressures During Intensive Unloading Therapy in Elderly With Decompensated Congestive Heart Failure and Preserved Left Ventricular Systolic Function

Background Plasma B-type natriuretic peptide (BNP) levels depend on left ventricular (LV) filling pressures and correlate with the state of neurohormonal modulation in patients with congestive heart failure (CHF). In these subjects, therapy of decompensated CHF can determine acute changes in BNP levels. Methods and Results We defined the sequential pattern of N-terminal (T) proBNP in elderly with decompensated CHF and preserved LV systolic function undergoing intensive unloading therapy, assessed the prevalence of patients who significantly reduced NTproBNP at the end of treatment, and verified the relations between changes in NTproBNP and ventricular filling pressures. NTproBNP was measured in 30 patients hospitalized for worsening CHF with LV ejection fraction >50% at admission and after 2 to 4 and 6 to 8 days from the start of treatment. Patients who exhibited a reduction in NTproBNP >35% from baseline to 8-day evaluation were defined as “responders.” Twelve healthy subjects matched for age and sex were used as controls. NTproBNP was significantly higher in CHF patients than controls in all time points, to a greater extent in baseline evaluation (2982 [lower/upper quartile 1273/8146] versus 235 [150/280] pg/mL). A progressive, linear reduction of NTproBNP was detected in CHF patients during unloading. At Day 8, 18 patients (60%) resulted in “responders,” whereas 12 (40%) were “nonresponders.” The former could be predicted through higher pulmonary artery wedge pressure at baseline. Surprisingly, ventricular filling pressures similarly declined in responders and non responders. At Day 8, NTproBNP was yet 7-fold higher in CHF patients than controls. Conclusion Intensive unloading therapy is associated with a significant short-term reduction in NTproBNP in elderly with CHF and preserved LV systolic function. This behavior is progressive and linear during the first week and parallels a reduction in ventricular filling pressures which, however, does not differ between patients who significantly reduce NTproBNP and those who do not. Thus the short-term changes in NTproBNP during intensive unloading therapy in our patients do not depend only on the acute improvement in hemodynamic conditions.