Pulmonary Arterial Compliance Research Articles

Pulmonary arterial compliance and exercise capacity after balloon pulmonary angioplasty in chronic thromboembolic pulmonary hypertension.

To determine whether changes in pulmonary vascular resistance (PVR) and changes in pulmonary artery compliance (C pa) are associated with changes in exercise capacity assessed either by changes in peak oxygen consumption (V'O2 ) or by changes in 6-min walk distance (6MWD) in patients with chronic thromboembolic pulmonary hypertension (CTEPH) undergoing balloon pulmonary angioplasty (BPA). Invasive haemodynamic parameters, peak V'O2 and 6MWD were measured within 24 h, before and after BPA (interval 3.1±2.4 months) in 34 CTEPH patients without significant cardiac and/or pulmonary comorbidities, of whom 24 received at least one pulmonary hypertension-specific treatment. C pa was calculated according to the pulse pressure method: C pa=((SV/PP)/1.76+0.1), where SV is the stroke volume and PP is the pulse pressure. The resistance-compliance (RC)-time of the pulmonary circulation was calculated as the PVR and C pa product. After BPA, PVR decreased (562±234 versus 290±106 dyn·s·cm-5; p<0.001); C pa increased (0.90±0.36 versus 1.63±0.65 mL·mmHg-1; p<0.001); but RC-time did not change (0.325±0.069 versus 0.321±0.083 s; p=0.75). There were improvements in peak V'O2 (1.11±0.35 versus 1.30±0.33 L·min-1; p<0.001) and in 6MWD (393±119 versus 432±100 m; p<0.001). After adjustment for age, height, weight and gender, changes in exercise capacity, assessed either by peak V'O2 or 6MWD, were significantly associated with changes in PVR, but not with changes in C pa. Contrary to what has been reported in CTEPH patients undergoing pulmonary endarterectomy, in CTEPH patients undergoing BPA, changes in exercise capacity were not associated with changes in C pa.

Lung diffusion capacity correlates with pre-implant pulmonary hypertension and predicts outcome after LVAD implantation.

Diffusing capacity of the lung for carbon monoxide (DLCO ) reduction is common in heart failure (HF) and is associated with a worse prognosis. Correlations between DLCO and pulmonary hypertension (PH) are unclear, and published data are conflicting; it has been shown that DLCO impairment may persist or even worsen after normalization of pulmonary pressures following left ventricle assist device (LVAD) implantation, maybe reflecting persistent pulmonary damage. We aimed to investigate the impact of pre-implant DLCO and central haemodynamics on outcome in patients with advanced HF implanted with a LVAD. We retrospectively analysed pre-implant and post-implant data from 42 patients implanted with a LVAD at our institution. Out of 42 patients, 35 had post-capillary PH before implantation, including 17 with combined post- and pre-capillary PH (Cpc-PH). Median DLCO was 59% (IQR 47-68%), and it inversely correlated with pulmonary vascular resistance (PVR) (P 0.037) and diastolic pulmonary gradient (DPG) (P 0.042). Compared with baseline, LVAD resulted in improvement in LV diameter (LVDd, P<0.001), mitral regurgitation (P 0.022), and PH (mPAP 24 vs. 36mmHg, P<0.001; PAWP 12 vs. 23mmHg, P 0.001; pulmonary artery compliance, CPA 3.1 vs. 1.9mL/mmHg, P 0.021). Lower DLCO and Cpc-PH at baseline were associated with a better LV reverse remodelling post-implantation (P 0.027 for LVDd) but also with a smaller gain in CPA (P 0.049). Before LVAD implantation, DLCO impairment is associated with higher PVR and DPG, suggesting that it might be an expression of persistent pulmonary damage occurring in Cpc-PH. After LVAD implantation, both LV dimension and haemodynamics improve. Lower pre-implant DLCO is associated with better LV reverse remodelling.

Abstract 10541: Borderline Elevated Pulmonary Artery Pressures Not Meeting Criteria for Pulmonary Hypertension in Patients With Idiopathic Pulmonary Fibrosis is Associated With Lower Transplant-Free Survival

Introduction: Pulmonary hypertension (PH) in Idiopathic Pulmonary Fibrosis (IPF) is associated with poor outcomes. The hemodynamic definition of PH was revised from a mean pulmonary artery pressure (mPAP) ≥25 mmHg to &gt;20 mmHg. We sought to explore the implications of these criteria in patients with IPF with a focus on outcomes in those with an elevated mPAP not meeting criteria for Pre- or Post-capillary PH, herein termed Borderline PH. Methods: We identified patients with IPF who underwent chest CT, transthoracic echocardiography (TTE), and right heart catheterization (RHC) using the Mass General Brigham Research Patient Data Repository. Medical records were reviewed to confirm the diagnosis of IPF. Established hemodynamic criteria categorized patients by PH status. Patients with elevated mPAP &gt;20 mmHg not meeting the definition of Pre-capillary PH (PVR ≥3 Wood Units) or Post-capillary PH (PCWP ≥15 mmHg) were defined as Borderline PH. Categorical variables were assessed using Chi-squared, Continuous variables using Wilcoxon Rank-Sum, and transplant-free survival using Kaplan-Meier analysis and Gehan-Breslow-Wilcoxon test. Results: 212 patients were identified: PH Present (n=92), Borderline PH (n=45), and PH Absent (n=75). One year from RHC, transplant-free survival was lower in patients with PH Present (n=37/92, 40%; p = 0.0002) or Borderline PH (n=20/45, 45%; p = 0.009) compared to those without PH (n=49/75, 65%) (Figure 1). Additionally, patients with Borderline PH had lower Pulmonary Artery Pulsatility Index (3.6 (3.0-6.0) vs 6.5 (4.2-10.5); p &lt; 0.001), Pulmonary Artery Compliance (3.9 (3.2-4.6) vs 4.5 (3.4-5.8) mL/mmHg; p = 0.012), and an elevated Right Ventricular Stroke Work Index (9.9 (8.5-11.6) vs 7.3 (5.7-8.7) mmHg*mL/m 2 ; p &lt; 0.001) versus those without PH. Conclusions: In this retrospective study of patients with IPF, those with Borderline PH had lower rates of transplant-free survival and worse derived hemodynamics compared to those without PH.

Abstract 13442: Right Ventricular Outflow Tract Doppler Notching: A Sensitive Non-Invasive Discriminator of Pulmonary Vascular Disease in Patients With Heart Failure With Preserved Ejection Fraction

Introduction: Pulmonary hypertension (PH) in the setting of heart failure with preserved ejection fraction (PH-HFpEF) is further characterized as isolated post-capillary PH (IpcPH) or combined pre- &amp; post-capillary PH (CpcPH). This is distinguished by pulmonary vascular resistance (PVR) cut-off of 3 WU. Prior definitions used a diastolic pulmonary gradient (DPG) cut-off of 7mmHg to distinguish PH subtype. Studies have examined echocardiographic right ventricular outflow tract Doppler notching (RVOT-notch) as a correlate for pulmonary vascular disease, though its role in distinguishing PH-HFpEF subtype by current vs. prior definition has never been described. Hypothesis: Our study explores the ability of RVOT-notch to distinguish CpcPH from IpcPH in patients with PH-HFpEF, in the context of current PVR &amp; prior DPG cutpoints. Methods: We retrospectively reviewed patients with PH-HFpEF referred to our PH program who underwent right heart catheterization and echo (later reviewed independently by blinded cardiologists to assess RVOT-notch). Results: 86 patients with PH-HFpEF were reviewed with a mean age of 66 and female predominance. Patients with RVOT-notch had signs of worsening right heart function both via echocardiography (higher estimated PASP, more severe TR, lower TAPSE) &amp; hemodynamically (higher DPG, higher PVR, and lower pulmonary arterial compliance). RVOT-notch was able to distinguish CpcPH from IpcPH, with current PVR cut-off ≥3 WU (sensitivity 91%, specificity 68%, PPV 76%, NPV 88%) and prior DPG cut-off ≥7mmHg (sensitivity of 94%, specificity 58%, PPV 57%, NPV 94%). Conclusions: In PH-HFpEF, RVOT-notch is a sensitive marker of CpcPH, and notably better reflects the current PVR-based definition (PVR≥3) with better specificity than prior DPG-based definition. This could have implications as non-invasive screening for CpcPH in patients with PH-HFpEF. Further work is needed to validate this marker in larger cohorts.

Pulmonary arterial compliance in patients of CHD with increased pulmonary blood flow.

Pulmonary arterial compliance, the dynamic component of pulmonary vasculature, remains inadequately studied in patients with left to right shunts. We sought to study the pulmonary arterial compliance in patients with left to right shunt lesions and its utility in clinical decision-making. In this single-centre retrospective study, we reviewed cardiac catheterisation data of consecutive patients of left to right shunt lesions catheterised over one year. In addition to the various other parameters, pulmonary arterial compliance was calculated, as indexed pulmonary flow (Qpi) / (Heart rate × pulse pressure in the pulmonary artery). RC time was also calculated, as the product of pulmonary arterial compliance and pulmonary vascular resistance index. Patients were divided into "operable," "borderline," and "inoperable" based on the decision of the treating team, and the pulmonary arterial compliance values were evaluated in these groups to study if it can be utilised to refine the operability decision. 298 patients (Median age 16 years, 56% <18 years) with various acyanotic shunt lesions were included. Overall, the pulmonary arterial compliance varied with Qpi, pulmonary artery mean pressure, and pulmonary vascular resistance index, but did not vary with age, type of lesion, or transpulmonary gradients. The median pulmonary arterial compliance in patients with normal pulmonary artery pressure (Mean pulmonary artery pressure less than 20 mmHg) was 4.1 ml/mmHg/m2 (IQR 3.2). The median pulmonary arterial compliance for operable patients was 2.67 ml/mmHg/m2 (IQR 2.2). Median pulmonary arterial compliance was significantly lower in both inoperable (0.52 ml/mmHg/m2, IQR 0.34) and borderline (0.80 ml/mmHg/m2, IQR 0.36) groups when compared to operable patients (p < 0.001). A pulmonary arterial compliance value lower than 1.18 ml/mmHg/m2 identified inoperable patients with high sensitivity and specificity (95%, AUC 0.99). However, in borderline cases, assessment by this value did not agree with empirical clinical assessment.The median RC time for the entire study population was 0.47 S (IQR 0.30). RC time in operable patients was significantly lower than that in the inoperable patients (Median 0.40 IQR 0.23 in operable, 0.73 0.25 in inoperable patients (p < 0.001). Addition of pulmonary arterial compliance to the routine haemodynamic assessment of patients with shunt lesions may improve our understanding of the pulmonary circulation and may have clinical utility.

Effects of remote haemodynamic-guided heart failure management in patients with different subtypes of pulmonary hypertension: insights from the MEMS-HF study.

The CardioMEMS European Monitoring Study for Heart Failure (MEMS-HF) investigated safety and efficacy of pulmonary artery pressure (PAP)-guided remote patient management (RPM) in New York Heart Association (NYHA) class III outpatients with at least one heart failure hospitalization (HFH) during the previous 12 months. This pre-specified subgroup analysis investigated whether RPM effects depended on presence and subtype of pulmonary hypertension (PH). In 106/234 MEMS-HF participants, Swan-Ganz catheter tracings obtained during sensor implant were available for off-line manual analysis jointly performed by two experts. Patients were classified into subgroups according to current PH definitions. Isolated post-capillary PH (IpcPH) and combined post- and pre-capillary PH (CpcPH) were present in 38 and 36 patients, respectively, whereas 31 patients had no PH. Clinical characteristics were comparable between subgroups, but among patients with PH pulmonary vascular resistance was higher (p= 0.029) and pulmonary artery compliance lower (p= 0.003) in patients with CpcPH. During 12 months of PAP-guided RPM, all PAPs declined in IpcPH and CpcPH subgroups (all p< 0.05), whereas only mean and diastolic PAP decreased in patients without PH (both p< 0.05). Improvements in post- versus pre-implant HFH rates were similar in CpcPH (0.639 events/patient-year; hazard ratio [HR] 0.37) and IpcPH (0.72 events/patient-year; HR 0.45) patients. Participants without PH benefited most (0.26 events/patient-year; HR 0.17, p= 0.04 vs. IpcPH/CpcPH patients). Quality of life and NYHA class improved significantly in all subgroups. Outpatients with NYHA class III symptoms with at least one HFH during 1 year pre-implant benefitted significantly from PAP-guided RPM during post-implant follow-up irrespective of presence or subtype of PH at baseline.

Comparative prognostic value of parameters of right ventricular pulsatile afterload in patients with advanced heart failure awaiting heart transplantation

Abstract Background Right ventricular (RV) function demonstrated a strong impact on survival of patients with advanced heart failure with reduced ejection fraction (HFrEF). In particular, increased RV pulsatile afterload (RVPA) was associated with poor prognosis. Several right heart catheterization-derived parameters have been proposed to characterize RVPA, including pulmonary artery compliance (PAC), elastance (PAE) and pulsatile index (PAPi). However, among these indices, the best prognostic indicator is undetermined. Purpose To assess the prognostic relevance of RVPA parameters in patients with advanced HFrEF evaluated for heart transplantation. Methods 149 patients with end-stage HFrEF underwent right heart catheterization during the evaluation for heart transplantation. All patients were clinically followed up until death or any censoring events including heart transplantation, left ventricular assist device (LVAD) and hospitalization for acute heart failure. Cox regression and ROC-curve analysis were used to test the prognostic value of RVPA determinants. Multivariate regression models with C-statistics were used to test the independent predictive value of RVPA indices. Results The mean age of the study population was 56.6±10.1 years and 85.2% were male. The most frequent aetiology of HFrEF was ischemic cardiomyopathy (52.3%). Mean LV ejection fraction was 25.7±10.2%. During a mean follow up time of 17±15 months, 29 (19.5%) patients met the primary endpoint: 9 (6%) patients died, 4 (2.68%) patients underwent an urgent heart transplantation, 11 (7.3%) patients underwent urgent LVAD implantation (as bridge to transplantation therapy) and 5 (3.3%) were hospitalized for HF. Patients who met the primary endpoint were significantly older patients (61.2±7.8 vs 55.4±10.2, p=0.006) and with worse hemodynamic profile than event-free survivors (PAC [1.8±0.8 vs. 2.7±2.0, p=0.01], mPAP [33.5±11.3 vs. 29.3±11.0, p=0.05], PVR [3.0±1.6 vs. 2.6±2.0, p=0.09] and PAE [1.12±0.5 vs. 0.98±0.6, p=0.04]). Among the RVPA parameters PAC&amp;lt;1.9 mL/mmHg (HR 4.0, CI 1.3–6.0, p=0.007) and PAE&amp;gt;0.9 mmHg/mL (HR 2.5, 95% CI 1.1–5.2, p=0.02) were associated with the primary endpoint. On the contrary, PAPi was not significantly associated with the outcome. PAC demonstrated a superior predictive value for the composite adverse outcome compared with pulmonary vascular resistances (PVR) (AUC comparison p=0.019) and PAPi (p=0.03) but similar compared with PAE (p=0.19) and mPAP (p=0.51). In multivariable regression models, PAC, but not PAE showed incremental prognostic value compared with cardiac index (p=0.02). Conclusions Hemodynamic indices of RVPA are associated with worse survival in patients with end-stage heart failure. In particular, PAC and PAE demonstrated superior prognostic value compared with PAPi and steady-state PVR. Moreover, PAC showed incremental prognostic value compared with cardiac index in patients awaiting heart transplantation. Funding Acknowledgement Type of funding sources: None.

An updated meta-analysis of hemodynamics markers of prognosis in patients with pulmonary hypertension due to left heart disease

Abstract Background Pulmonary hypertension (PH) is associated with a poor prognosis in patients with left heart disease (LHD). Several hemodynamic variables have been shown to predict outcome, including pulmonary vascular resistance (PVR), pulmonary artery compliance (PAC), and the diastolic pressure gradient (DPG). We sought to provide an updated analysis on the association of these variables with prognosis in PH-LHD. Methods We performed a systematic literature review including studies reporting association measurements between DPG and/or PVR and/or PAC and death in PH-LHD patients. These hemodynamic variables were extracted to estimate the pooled hazard ratio (HR) of adverse outcome for each one, and cumulative meta-analysis was performed to investigate temporal trends in the effects reported in the literature as well as the impact of sample size. Results 17 articles were identified, including 9716 patients with LHD, heterogeneous in terms of age, sex, and etiology of cardiac disease. In this large population, we found that PVR (HR, 1.09; 95% CI: 1.06–1.12), DPG (HR, 1.02; 95% CI: 1.01–1.02) and PAC (HR, 0.73; 95% CI: 0.76–0.81) were associated with an increased risk of adverse outcome, albeit with a less solid performance of DPG (Figure 1). Similar results were found when hemodynamic variables were analyzed according to the thresholds commonly applied in clinical practice, or subdividing cohorts according to the underlying LHD (either heart failure with preserved or reduced left ventricular ejection fraction, or valvular heart disease). Furthermore, cumulative metanalysis indicated that these results are consistently stable since 2018 (Figure 2). Conclusions Despite the heterogeneity of PH-LHD group and the intrinsic limitations of each variable, PVR, DPG, and PAC have an established prognostic value in PH-LHD. The strongest correlation with PVR and PAC supports their use in defining disease severity and identifying a subgroup of patients at higher risk of adverse outcome. We believe that these results are consistent through the years and unlikely to change with the addition of further studies. Funding Acknowledgement Type of funding sources: Private grant(s) and/or Sponsorship.

Right ventricular myocardial work in patients undergoing left ventricular assist device implant

Abstract Background Right ventricular failure (RVF) complicates 10 to 40% of left ventricular assist device (LVAD) implants, with necessity of high dose inotropic/vasodilatory drugs and right ventricular assist devices in severe cases. Prevention of RVF starts with appropriate patient selection for LVAD implant through extensive clinical, echocardiographic and hemodynamic evaluation. Purpose This study aimed to evaluate the performance of a novel non-invasive echocardiographic method for estimation of right ventricular myocardial work to predict RVF and death after LVAD implant. Methods Consecutive patients from May 2017 to February 2022 undergoing LVAD implant were retrospectively reviewed. Patients without a useful echocardiographic exam and/or a right heart catheterization prior to LVAD implant were excluded. Myocardial work analysis by Speckle Tracking Echocardiography (STE) was performed in these patients. The primary endpoints were RVF and death. Results The study included 23 patients (mean age 64±8 years, 91% men). Median follow-up time was 304 days (IQR: 23–1017). GWI significantly correlated with invasively-derived right ventricular stroke work index (RVSWI, r=0.538; p=0.008) and pulmonary arterial compliance (PAC, r=−0.522; p=0.013). Patients who experienced RVF (26.1%) had lower GWI (p=0.047) and GWE (p=0.001) and higher GWW (p=0.001). Patients who experienced death at 30 days after LVAD implant (26.1%) had lower GWE (p=0.005) and higher GWW (p=0.006). Performance for prediction of RVF after LVAD implant was greatest for GWE (AUC 0.92), followed by GWW (AUC 0.88) and GWI (AUC 0.78). A cut-off of 77% for GWE have a 100% sensibility and 82% specificity for prediction of RVF. At long term follow-up, death occurred in 4 patients (29%) in the GWE&amp;gt;77% group and in 6 patients (67%) in the GWE&amp;lt;77% group (hazard ratio for death, 0.24; 95% CI, 0.07 to 0.89, p=0.032). Conclusions Right ventricular myocardial work is a strong predictor of RVF after LVAD implant and death at long-term follow up. Its calculation should be implemented in the evaluation for LVAD candidacy. Funding Acknowledgement Type of funding sources: None.

An updated meta-analysis of hemodynamics markers of prognosis in patients with pulmonary hypertension due to left heart disease.

Pulmonary hypertension (PH) is associated with a poor prognosis in left heart disease (LHD). We sought to provide an updated analysis on the association of hemodynamic variables, such as pulmonary vascular resistance (PVR), pulmonary artery compliance (PAC), and diastolic pressure gradient (DPG), with prognosis in PH-LHD, through a systematic literature review. Sixteen articles were identified, including 9600 patients with LHD, heterogeneous in terms of age, sex, and etiology of cardiac disease. In this large population, PVR (hazard ratio [HR], 1.07; 95% confidence interval [CI]: 1.05-1.0), DPG (HR, 1.02; 95% CI: 1.01-1.02) and PAC (HR, 0.76; 95% CI: 0.69-0.84) were associated with an increased risk of adverse outcome, albeit with a less solid performance of DPG. Similar results were found when hemodynamic variables were analyzed according to the thresholds commonly applied in clinical practice, or subdividing cohorts according to the underlying LHD. Furthermore, cumulative metanalysis indicated that these results are consistently stable since 2018. Thus, PVR, DPG and PAC have an established prognostic value in PH-LHD. These results are consistent through the years and unlikely to change with further studies.

Low Pulmonary Artery Pulsatility Index by Echocardiography Is Associated With Increased Mortality in Pulmonary Hypertension

Pulmonary hypertension (PH) is a progressive pulmonary vascular disorder with elevated mortality risk. The pulmonary artery (PA) pulsatility index (PAPi) based on invasively acquired parameters has emerged as a hemodynamic risk predictor. Whether noninvasively derived PAPi (PA pulse pressure divided by right atrial pressure) is valuable is unclear. Consecutive patients undergoing transthoracic echocardiography for known or suspected PH were included with conventional echocardiographic measures of PA systolic, PA diastolic, and estimated right atrial pressures. In those patients with PH (mean PA pressure > 20mm Hg), PAPi was divided into 3 groups: <1.5, 1.5 to 3, and >3. Mortality was assessed over 5years. Of 1,045 patients enrolled, 64% had PH. Patients with the lowest PAPi had higher N-terminal-pro hormone B-type natriuretic peptide levels, larger right ventricles (RVs), worse RV systolic function, and greater degrees of tricuspid regurgitation. In patients with PH, PAPi was inversely proportional to the risk of death, with PAPi <3 associated with a 1.96-fold increased risk of death (95% CI, 1.45-2.64, P<.0001). At multivariate analysis, RV longitudinal systolic strain (hazard ratio [HR]=1.45, 1.24-1.71; P<.0001), PAPi <3 (HR=1.76, 1.31-2.37; P=.0002), and the presence of a pericardial effusion (HR=1.64, 1.20-2.26 P=.003) were independently associated with increased mortality. In age- and sex-adjusted models, PAPi was incremental to PA compliance. In patients with PH, low PAPi derived noninvasively by transthoracic echocardiography is associated with markers of right heart failure, RV dysfunction, and worse survival. PAPi could be incorporated into the conventional echo parameters reported in patients with PH and may be a useful predictor of outcome.

Comparative Prognostic Value of Parameters of Pulsatile Right Ventricular Afterload in Patients With Advanced Heart Failure Awaiting Heart Transplantation

Right ventricular pulsatile afterload (RVPA) demonstrated a strong impact on survival of patients with advanced heart failure (HF) with reduced ejection fraction. The best prognostic parameter of RVPA is unknown. The aim of this work was to examine the prognostic relevance of pulmonary artery compliance (PAC), pulmonary artery elastance (PAE), and pulmonary artery pulsatile index (PAPi) in a consecutive cohort of patients with advanced HF evaluated for heart transplantation (HT). A total of 149 patients with end-stage HF underwent right-sided cardiac catheterization and were clinically followed up until death or any censoring events, including HT, left ventricular assist device, and hospitalization for acute HF. The primary endpoint occurred in 29 patients (19.5%) during a median follow-up time of 12 (interquartile range 3 to 34) months. This cohort presented a worse hemodynamic profile than event-free survivors. PAC <1.9 mL/mm Hg (hazard ratio 3, 95% confidence interval 1.3 to 6.0, p=0.007) and PAE >0.9 mmHg/mL (hazard ratio 2.5, 95% confidence interval 1.1 to 5.2, p=0.02) were associated with the adverse outcome. On the contrary, PAPi was not associated with the outcome. PAC demonstrated a superior predictive value for the composite adverse outcome compared with pulmonary vascular resistance (area under the curve comparison p=0.019) and PAPi (p=0.03) but similar compared with PAE (p=0.19) and mean pulmonary arterial pressure (p=0.51). PAC, but not PAE, showed incremental prognostic value compared with cardiac index (p=0.02). In conclusion, hemodynamic indexes of RVPA are associated with worse survival in patients with end-stage HF. PAC and PAE demonstrated superior prognostic value compared with PAPi and pulmonary vascular resistance. Moreover, PAC showed incremental prognostic value compared with cardiac index in patients awaiting HT.

Prognostic meaning of right ventricular function and output reserve in patients with systemic sclerosis

BackgroundThe objective of this study was to investigate the prognostic impact of right ventricular (RV) function at rest and during exercise in patients with systemic sclerosis (SSc) presenting for a screening for pulmonary hypertension (PH).MethodsIn this study, data from SSc patients who underwent routinely performed examinations for PH screening including echocardiography and right heart catheterization at rest and during exercise were analysed. Uni- and multivariable analyses were performed to identify prognostic parameters.ResultsOut of 280 SSc patients screened for PH, 225 were included in the analysis (81.3% female, mean age 58.1±13.0 years, 68% limited cutaneous SSc, WHO-FC II–III 74%, 24 manifest PH). During the observation period of 3.2±2.7 (median 2.6) years 35 patients died. Tricuspid annular plane systolic excursion (TAPSE) at rest <18 mm (p=0.001), RV output reserve as increase of cardiac index (CI) during exercise <2 l/min (p<0.0001), RV pulmonary vascular reserve (Δ mean pulmonary artery pressure/Δ cardiac output) ≥3 mmHg/l/min (p<0.0001), peak CI <5.5 l/min/m2 (p=0.001), pulmonary arterial compliance <2 ml/mmHg (p=0.002), TAPSE/systolic pulmonary arterial pressure (sPAP) ratio ≤0.6 ml/mmHg (p<0.0001) and echocardiographic qualitative RV function at rest (p<0.0001) significantly predicted worse survival. In the multivariable analysis TAPSE/sPAP ratio and diffusion capacity for carbon monoxide ≤65% were identified as independent prognostic predictors and had 75% sensitivity and 69% specificity to predict future development of pulmonary vascular disease (PVD) during follow-up.ConclusionsThis study demonstrates that assessment of RV function at rest and during exercise may provide crucial information to identify SSc patients who are at a high risk of poor outcome and for the development of PH and/or PVD.

Pulmonary artery acceleration time in young children is determined by heart rate and transpulmonary gradient but not by pulmonary blood flow: A simultaneous echocardiography—cardiac catheterization study

Pulmonary artery acceleration time (PAAT) is considered useful for the non-invasive evaluation of pulmonary artery pressure (PAP) and pulmonary vascular resistance (PVR). PAAT is dependent on PAP, PVR, pulmonary artery compliance, stroke volume, and heart rate. Its relative dependency on these determinants may differ between young and older children, raising uncertainty regarding its utility in young children. We aim to identify the primary determinants of the PAAT in children less than 36 months undergoing cardiac catheterization and its utility for the diagnosis of elevated PVR. We prospectively studied 42 children undergoing cardiac catheterization and simultaneous echocardiography. We determined the correlations of PAAT to the above-mentioned determinants and evaluated receiver operator characteristic (ROC) curves for diagnosis of PVR indexed to body surface area (PVRi) ≥3 Wu*m2 . Median age was 11.5 (IQR 5.2, 21.2) months. Moderate correlations were found between PAAT and mean PAP (R = -.66, p < .001), PVRi (R = -.54, p = .004), pulmonary artery compliance (R = .65, p < .001), transpulmonary gradient (R = -.67, p < .001), stroke volume (R = .61, p = .002), and heart rate (R = -.63, p < .001). In multivariate regression modeling, only transpulmonary gradient and heart rate were independent determinants of PAAT. PAAT ≤77 msec had acceptable utility for diagnosing PVRi ≥ 3 Wu*m2 (AUC .8 [.64, .95], n = 36), low sensitivity (59%), and excellent specificity (94%). Transpulmonary gradient and heart rate, but not pulmonary blood flow, are important determinants of PAAT in children <36 months undergoing cardiac catheterization. PAAT has low sensitivity for diagnosing elevated PVRi, therefore, should not be solely relied upon in screening for elevated PVRi in young children.

Right Ventricular Dyssynchrony in Patients With Chronic Thromboembolic Pulmonary Hypertension and Pulmonary Arterial Hypertension.

Chronic thromboembolic pulmonary hypertension (CTEPH) and pulmonary arterial hypertension (PAH) are characterized by elevated pulmonary arterial pressure resulting in right heart failure. Right ventricular (RV) dyssynchrony may be associated with early-stage RV dysfunction; however, the differences in RV dyssynchrony between CTEPH and PAH and the factors contributing to RV dyssynchrony remain unclear.Methods and Results: Forty-four patients (CTEPH, 26; PAH, 18) were enrolled in this study. RV dyssynchrony was assessed by determining the standard deviation of the intervals from the peak QRS to peak systolic strain for 6 segments of the RV free and septal wall by using 2-dimensional speckle-tracking echocardiography (RV-6SD). The RV-6SD, pulmonary hemodynamics, echocardiographic findings, and patient demographics in CTEPH and PAH patients were compared and their correlations with RV-6SD were investigated. CTEPH patients were older and had significantly higher pulse pressure of the pulmonary artery (PP), tricuspid valve regurgitation pressure gradient, and RV-6SD, and lower pulmonary arterial compliance (PAC), despite showing comparable pulmonary arterial pressures. Age-adjusted multiple logistic analysis showed that RV-6SD and PAC were predictors of CTEPH rather than PAH. RV-SD6 was positively correlated with PP and RV dimension and negatively correlated with PAC. CTEPH patients showed more evident RV dyssynchrony than PAH patients. Low PAC and a widened PP may delay RV free wall motion and cause RV dyssynchrony.

RC time (resistance×compliance) is related to residual symptom after pulmonary endarterectomy in chronic thromboembolic pulmonary hypertension.

BackgroundRight ventricular (RV) afterload is widely assessed by pulmonary vascular resistance (PVR). However, RV afterload is underestimated because PVR does not account for the pulsatile load. The pulsatile load is often evaluated by pulmonary arterial compliance (PAC). The RC (resistance-compliance) time, which is calculated from the product of PVR and PAC, is considered to remain constant under medical therapy. However, little is known on how RC time is affected by invasive therapy in chronic thromboembolic pulmonary hypertension (CTEPH). This study aimed to evaluate change of RC time in patients underwent pulmonary endarterectomy (PEA). Furthermore, we investigated the clinical relevance of RC time.MethodsWe reviewed consecutive 50 patients except for death case underwent PEA. Baseline clinical parameters including RC time before performing PEA and follow-up were evaluated. Patients was classified as decrease or non-decrease according to change of RC time. Furthermore, we classified patients into a NYHA I group who had no symptom after treatment and a residual symptom group in order to investigate the relationship of RC time to residual symptoms.ResultsRC time was significantly decreased after PEA (0.54 ± 0.16 to 0.45 ± 0.12 sec, p < 0.001). Residual symptom after PEA of Decrease group were significantly better than that of Non-decrease group in RC time (12 patients, 40% vs. 11 patients, 78.6%, p < 0.02). Furthermore, multivariate analysis revealed that only RC time after PEA was independently associated with residual symptom (OR 1.026, 95% CI 1.005–1.048; p = 0.017).ConclusionsRC time was decreased after PEA, and might be a possible indicator for predicting PEA success.

Impact of Recipients Pre-Operative Right Ventricular Dysfunction on Heart Transplantation Outcomes

Purpose To evaluate the impact of recipients pre-operative right ventricular dysfunction on heart transplantation (Htx) outcomes. Methods We retrospectively analyzed 517 consecutive adult patients who underwent Htx between January 2000 and December 2020, focusing on right heart catheter hemodynamic data, mostly. Results In-hospital mortality was 8%. Severe Early Graft Failure (EGF) occurred in 6.6% of patients. Right ventricular function and pulmonary circulation hemodynamic variables were weighted in terms of influence on in-hospital mortality: Central Venous Pressure (CVP) [OR 1.09 (1.03;1.15), p=0.004], Pulmonary Artery Systolic Pressure (PASP) [OR 1.02 (1.00;1.04), p=0.05], CVP/ Pulmonary Capillary Wedge Pressure (PCWP) ratio [OR 2.78 (1.14;6.80), p=0.025], Pulmonary Vascular Resistance (PVR) [OR 1.15 (1.01;1.32), p=0.042], Trans-Pulmonary Gradient (TPG) [OR 1.11 (1.03;1.18), p=0.003] and Diastolic Trans-Pulmonary Gradient (DPG) [OR 1.10 (1.02;1.20), p=0.015]. Thereafter, PASP [OR 1.03 (1.00;1.05), p=0.016] and TPG [OR 1.08 (1.01;1.17), p=0.03] did impact negatively on the occurrence of EGF. Preoperative right ventricular dysfunction did not result to influence on follow-up (FU) mortality. On the multivariable analysis, CVP and TPG resulted to be independent predictors of in-hospital mortality while TPG of EGF. By spitting patients population into 4 hemodynamic profiles in terms of pulsatile load, focusing on Pulmonary Artery Compliance (PACi), and right ventricle hemodynamic response to load, focusing on CVP:PCWP ratio, we resulted to have a high PACi/high PVC:PCWP profile with a higher risk of in-hospital mortality [OR 2.40 (1.04;5.54), p=0.05] and EGF [OR 3.40 (1.32;7.28), p= 0.01]. Overall survival at 1, 5 and 10 years was 89.4%, 80.8% and 66.4%, respectively. By analyzing the four hemodynamic profiles, patients with low PACi/high PVC:PCWP showed the worst survival (Log-rank=0.045). Conclusion In our patients population, CVP and TPG resulted to be independent risk factors of in-hospital mortality while TPG of EGF. Thus, the detection of pre-operative right ventricular dysfunction in potential heart transplant recipients should be managed early and treated properly in terms of preoperative clinical optimization to improve the postoperative outcomes. To evaluate the impact of recipients pre-operative right ventricular dysfunction on heart transplantation (Htx) outcomes. We retrospectively analyzed 517 consecutive adult patients who underwent Htx between January 2000 and December 2020, focusing on right heart catheter hemodynamic data, mostly. In-hospital mortality was 8%. Severe Early Graft Failure (EGF) occurred in 6.6% of patients. Right ventricular function and pulmonary circulation hemodynamic variables were weighted in terms of influence on in-hospital mortality: Central Venous Pressure (CVP) [OR 1.09 (1.03;1.15), p=0.004], Pulmonary Artery Systolic Pressure (PASP) [OR 1.02 (1.00;1.04), p=0.05], CVP/ Pulmonary Capillary Wedge Pressure (PCWP) ratio [OR 2.78 (1.14;6.80), p=0.025], Pulmonary Vascular Resistance (PVR) [OR 1.15 (1.01;1.32), p=0.042], Trans-Pulmonary Gradient (TPG) [OR 1.11 (1.03;1.18), p=0.003] and Diastolic Trans-Pulmonary Gradient (DPG) [OR 1.10 (1.02;1.20), p=0.015]. Thereafter, PASP [OR 1.03 (1.00;1.05), p=0.016] and TPG [OR 1.08 (1.01;1.17), p=0.03] did impact negatively on the occurrence of EGF. Preoperative right ventricular dysfunction did not result to influence on follow-up (FU) mortality. On the multivariable analysis, CVP and TPG resulted to be independent predictors of in-hospital mortality while TPG of EGF. By spitting patients population into 4 hemodynamic profiles in terms of pulsatile load, focusing on Pulmonary Artery Compliance (PACi), and right ventricle hemodynamic response to load, focusing on CVP:PCWP ratio, we resulted to have a high PACi/high PVC:PCWP profile with a higher risk of in-hospital mortality [OR 2.40 (1.04;5.54), p=0.05] and EGF [OR 3.40 (1.32;7.28), p= 0.01]. Overall survival at 1, 5 and 10 years was 89.4%, 80.8% and 66.4%, respectively. By analyzing the four hemodynamic profiles, patients with low PACi/high PVC:PCWP showed the worst survival (Log-rank=0.045). In our patients population, CVP and TPG resulted to be independent risk factors of in-hospital mortality while TPG of EGF. Thus, the detection of pre-operative right ventricular dysfunction in potential heart transplant recipients should be managed early and treated properly in terms of preoperative clinical optimization to improve the postoperative outcomes.

Prognostic Power of Pulmonary Arterial Compliance Is Boosted by a Hemodynamic Unloading Test With Glyceryl Trinitrate in Heart Failure Patients With Post-capillary Pulmonary Hypertension.

BackgroundPulmonary hypertension (PH) is an established risk factor in patients with heart failure (HF). However, right heart catheterisation (RHC) and vasoreactivity testing (VRT) are not routinely recommended in these patients.MethodsThe primary objective of the present study was to explore the impact of VRT using sublingual glyceryl trinitrate (GTN) on transplant/ventricular assist device-free survival in HF patients with post-capillary PH. RHC parameters were correlated retrospectively with the primary outcome.ResultsThe cohort comprised 154 HF patients with post-capillary PH undergoing RHC with GTN-VRT at a tertiary heart failure centre. Multiple parameters were associated with survival. After adjustment for established prognosis-relevant clinical variables from the MAGGIC Score, variables with the most relevant odds ratios (OR) obtained after GTN-VRT were: calculated effective pulmonary arterial (PA) elastance (adjusted OR 2.26, 95%CI 1.30–3.92; p = 0.004), PA compliance (PAC-GTN; adjusted OR 0.45, 95%CI 0.25–0.80; p = 0.006), and total pulmonary resistance (adjusted OR 2.29, 95%CI 1.34–3.93; p = 0.003). Forest plot analysis including these three variables as well as PAC at baseline, delta PAC, and the presence of combined post- and pre-capillary PH revealed prognostic superiority of PAC-GTN, which was confirmed by Kaplan-Meier analysis.ConclusionsIn our cohort of symptomatic HF patients with post-capillary PH, improved PAC after administration of GTN was associated with survival independent of established hemodynamic and clinical risk factors. VRT using GTN may be better described as unloading test due to GTN's complex effects on the circulation. This could be used for advanced prognostication and should be investigated in further studies.

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.

Change in pulmonary arterial compliance and pulmonary pulsatile stress after balloon pulmonary angioplasty.

Although the underlying pathology of chronic thromboembolic pulmonary hypertension (CTEPH) is mechanical obliteration of the major pulmonary vessels, high pulsatile stress penetrating into the normal distal pulmonary microvasculature resulting from reduced pulmonary arterial compliance (CPA) may cause progressive deterioration in pulmonary hemodynamics. Hypothetically, balloon pulmonary angioplasty (BPA) may be beneficial in reducing CPA and pulsatile stress in patients with CTEPH. In total, 26 patients with available pre- and post-BPA right heart catheterization results were included in the study. BPA was performed in a series of staged procedures by 2 experienced interventional cardiologists. The median CPA showed a 59.2% increase (1.03 to 1.64 mL/mm Hg, p=0.005). The median pre-BPA pulsatile stress product decreased by 20.7% (4,266 to 3,380 mm Hg/min, p=0.003). A linear regression model established that the percent change in CPA after BPA accounted for 21.8% of the explained variability in the change in 6-minute walk test (p=0.009). Our results indicate that BPA decreases CPA and pulmonary pulsatile stress. These changes may be partly responsible for the improvement in functional capacity after BPA.