Lower Pulmonary Artery Compliance Research Articles

Association of pulmonary hypertension with the outcome in patients undergoing edge-to-edge mitral valve repair

ObjectivesThe association of pulmonary hypertension (PH) with the outcome after mitral transcatheter edge-to-edge repair (M-TEER) focusing on the new ESC/ERS guidelines definition for PH.BackgroundPH is frequently found in patients with...

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- & 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 & 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) & 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.

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.

MILD PULMONARY HYPERTENSION IN ADVANCED HEART FAILURE PATIENTS IS ASSOCIATED WITH BOTH ABNORMAL RESISTIVE AND PULSATILE LOAD AND LOWER 3-YEAR SURVIVAL

<h3>BACKGROUND</h3> Current guidelines require patients with heart failure (HF) being evaluated for advanced therapies such as heart transplantation or left ventricular assist device (LVAD) implantation to undergo right heart catheterization to identify the presence of pulmonary hypertension (PH). PH that is irreversible is a relative contraindication to heart transplantation and associated with poor prognosis. Based on the International Society for Heart and Lung Transplantation guidelines, reversibility is assessed with a vasodilator challenge if pulmonary artery systolic pressure (PASP) is > 50 mmHg, and either transpulmonary gradient (TPG) is > 15 mmHg or pulmonary vascular resistance (PVR) is > 3 WU. However, the most updated 6th World Symposium on Pulmonary Hypertension defined PH more broadly as to mean pulmonary artery pressure (mPAP) > 20 mmHg. As such, there is an intermediate group of patients with mild PH not meeting the threshold to receive a vasodilator challenge to determine whether mild PH is reversible. Our aim was to assess the hemodynamic characteristics of this group and determine whether they are at risk of worse clinical outcomes. <h3>METHODS AND RESULTS</h3> A retrospective analysis was performed of 175 patients with heart failure who were referred to our centre for right heart catheterization as part of evaluation for candidacy for advanced heart failure therapies. Patients were divided into three groups based on initial hemodynamics: patients with mPAP < 20 mmHg (No-PH, n=57), patients with significant PH meeting current guideline criteria for a vasodilator challenge (PH+V, n=41) and patients with mPAP > 20 mmHg that did not meet the threshold for vasodilator challenge (PH-V, n=77). Compared to the No-PH group, the PH-V group did not have a significantly different stroke volume index or cardiac index, however, they had a significantly higher PVR, indicating greater resistive load, and lower pulmonary artery compliance (PAC), indicating higher pulsatile load (Table). The PH-V group also had significantly higher mean right atrial pressure (mRAP) compared to the No-PH group, suggesting right ventricular decompensation. Composite pre-and post-intervention three-year survival after catheterization appeared lower in both PH+V and PH-V patients compared to the No-PH group (Figure). <h3>CONCLUSION</h3> HF patients assessed for advanced therapies identified as having mild PH have increased pulmonary pulsatile and resistive load, along with elevated right-sided filling pressures, and have increased mortality. Currently, this group does not undergo vasodilator testing to determine PH reversibility. Whether mild PH is modifiable, and its relationship to outcomes after heart transplantation or LVAD implant requires further study.

Association of obesity-related inflammatory pathways with lung function and exercise capacity

BackgroundObesity has multifactorial effects on lung function and exercise capacity. The contributions of obesity-related inflammatory pathways to alterations in lung function remain unclear.Research Question:To examine the association of obesity-related inflammatory pathways with pulmonary function, exercise capacity, and pulmonary-specific contributors to exercise intolerance. MethodWe examined 695 patients who underwent cardiopulmonary exercise testing (CPET) with invasive hemodynamic monitoring at Massachusetts General Hospital between December 2006–June 2017. We investigated the association of adiponectin, leptin, resistin, IL-6, CRP, and insulin resistance (HOMA-IR) with pulmonary function and exercise parameters using multivariable linear regression. ResultsObesity-related inflammatory pathways were associated with worse lung function. Specifically, higher CRP, IL-6, and HOMA-IR were associated with lower percent predicted FEV1 and FVC with a preserved FEV1/FVC ratio suggesting a restrictive physiology pattern (P ≤ 0.001 for all). For example, a 1-SD higher natural-logged CRP level was associated with a nearly 5% lower percent predicted FEV1 and FVC (beta −4.8, s.e. 0.9 for FEV1; beta −4.9, s.e. 0.8 for FVC; P < 0.0001 for both). Obesity-related inflammatory pathways were associated with worse pulmonary vascular distensibility (adiponectin, IL-6, and CRP, P < 0.05 for all), as well as lower pulmonary artery compliance (IL-6 and CRP, P ≤ 0.01 for both). InterpretationOur findings highlight the importance of obesity-related inflammatory pathways including inflammation and insulin resistance on pulmonary spirometry and pulmonary vascular function. Specifically, systemic inflammation as ascertained by CRP, IL-6 and insulin resistance are associated with restrictive pulmonary physiology independent of BMI. In addition, inflammatory markers were associated with lower exercise capacity and pulmonary vascular dysfunction.

Abstract 14287: Iron Deficiency is Associated With More Severe Pulmonary Vascular Disease in Pulmonary Hypertension Due to Chronic Lung Disease

Background: Iron deficiency promotes pulmonary vascular remodeling in pre-clinical models, and is associated with worse outcomes in pulmonary arterial hypertension. However, the consequences of iron deficiency in patients with pulmonary hypertension due to chronic lung disease (Group 3 PH) are unexplored. Methods: We studied 122 consecutive Group 3 PH patients from the University of Minnesota Pulmonary Hypertension Repository. Serum soluble transferrin receptor (sTR) levels quantified iron deficiency. We evaluated the relationship between iron deficiency and pulmonary vascular disease, right ventricular (RV) function, exercise capacity, and survival. Results: The iron deficient group (&lt;4.8mg/L sTR) had significantly higher mean pulmonary arterial pressure (40±9 mmHg, n=59 vs. 44±13 mmHg, n=61; p =.02) and lower pulmonary arterial compliance (2.2±1.2 mL/mmHg, n=52 vs. 1.7±0.8 mL/mmHg, n=55; p =.01), but there was no difference in pulmonary vascular resistance. Moreover, there were trends for higher right atrial pressure (7±4 mmHg, n=58 vs. 9±6 mmHg, n=61; p =0.08) in iron deficient patients. However, iron deficiency did not significantly alter RV function by echocardiography, 6-minute walk distance, or survival. Conclusions: Iron deficiency in Group 3 PH is associated with worse pulmonary vascular disease. This suggests iron deficiency could contribute to pulmonary vascular disease in Group 3 PH, and future studies are needed to determine if iron replacement could be a therapy for this deadly type of PH.

Comparison of pulmonary vascular resistance and pulmonary artery compliance during exercise between IPAH and CTEPH with normal pulmonary artery pressure

Abstract Background Pulmonary vascular resistance (PVR) and pulmonary artery compliance (PAC) are inversely related. However, the little is known about dynamics during exercise by disease difference. The aim of this study was to reveal the relationships of PVR and PAC during exercise between idiopathic pulmonary arterial hypertension (IPAH) and chronic thromboembolic pulmonary hypertension (CTEPH) patients. Methods Sixty-two IPAH patients (45±9 y.o) and 359 CTEPH patients (63±13 y.o) with normal mean PAP and PAWP at rest underwent symptom-limited exercise test using supine cycle ergometer with right heart catheter. Results There were no differences between baseline mean PAP and PAWP in 2 groups, however, cardiac output, SaO2 and SvO2 were lower in CTEPH group. Lower PAC (2.9±1.1 vs. 3.7±1.7 ml/mmHg, p&amp;lt;0.001) and higher PVR (2.3±1.0 vs. 1.9±1.0 wood.unit, p=0.016) were observed in CTEPH group. These trends were also seen at peak exercise. PVR-PAC relationship in CTEPH group was leftward shift compared with IPAH group (Figure 1). Conclusion Resting and exercise PVR and PAC in CTEPH patients were worse than those in IPAH patients who had normal PAP and PAWP at rest. Figure 1 Funding Acknowledgement Type of funding source: None

Pulmonary vascular dysfunction among people aged over 65 years in the community in the Atherosclerosis Risk In Communities (ARIC) Study: A cross-sectional analysis.

Heart failure (HF) risk is highest in late life, and impaired pulmonary vascular function is a risk factor for HF development. However, data regarding the contributors to and prognostic importance of pulmonary vascular dysfunction among HF-free elders in the community are limited and largely restricted to pulmonary hypertension. Our objective was to define the prevalence and correlates of abnormal pulmonary pressure, resistance, and compliance and their association with incident HF and HF phenotype (left ventricular [LV] ejection fraction [LVEF] ≥ or < 50%) independent of LV structure and function. We performed cross-sectional and time-to-event analyses in a prospective epidemiologic cohort study, the Atherosclerosis Risk in Communities study. This is an ongoing, observational study that recruited 15,792 persons aged 45-64 years between 1987 and 1989 (visit 1) from four representative communities in the United States: Minneapolis, Minnesota; Jackson, Mississippi; Hagerstown, Maryland; and Forsyth County, North Carolina. The current analysis included 2,810 individuals aged 66-90 years, free of HF, who underwent echocardiography at the fifth study visit (June 8, 2011, to August 28, 2013) and had measurable tricuspid regurgitation by spectral Doppler. Echocardiography-derived pulmonary artery systolic pressure (PASP), pulmonary vascular resistance (PVR), and pulmonary arterial compliance (PAC) were measured. The main outcome was incident HF after visit 5, and key secondary end points were incident HF with preserved LVEF (HFpEF) and incident HF with reduced LVEF (HFrEF). The mean ± SD age was 76 ± 5 years, 66% were female, and 21% were black. Mean values of PASP, PVR, and PAC were 28 ± 5 mm Hg, 1.7 ± 0.4 Wood unit, and 3.4 ± 1.0 mL/mm Hg, respectively, and were abnormal in 18%, 12%, and 14%, respectively, using limits defined from the 10th and 90th percentile limits in 253 low-risk participants free of cardiovascular disease or risk factors. Left heart dysfunction was associated with abnormal PASP and PAC, whereas a restrictive ventilatory deficit was associated with abnormalities of PASP, PVR, and PAC. PASP, PVR, and PAC were each predictive of incident HF or death (hazard ratio per SD 1.3 [95% CI 1.1-1.4], p < 0.001; 1.1 [1.0-1.2], p = 0.04; 1.2 [1.1-1.4], p = 0.001, respectively) independent of LV measures. Elevated pulmonary pressure was predictive of incident HFpEF (HFpEF: 2.4 [1.4-4.0, p = 0.001]) but not HFrEF (1.4 [0.8-2.5, p = 0.31]). Abnormal PAC predicted HFrEF (HFpEF: 2.0 [1.0-4.0, p = 0.05], HFrEF: 2.8 [1.4-5.5, p = 0.003]), whereas abnormal PVR was not predictive of either (HFpEF: 0.9 [0.4-2.0, p = 0.85], HFrEF: 0.7 [0.3-1.4, p = 0.30],). A greater number of abnormal pulmonary vascular measures was associated with greater risk of incident HF. Major limitations include the use of echo Doppler to estimate pulmonary hemodynamic measures, which may lead to misclassification; inclusions bias related to detectable tricuspid regurgitation, which may limit generalizability of our findings; and survivor bias related to the cohort age, which may result in underestimation of the described associations. In this study, we observed abnormalities of PASP, PVR, and PAC in 12%-18% of elders in the community. Higher PASP and lower PAC were independently predictive of incident HF. Abnormally high PASP predicted incident HFpEF but not HFrEF. These findings suggest that impairments in pulmonary vascular function may precede clinical HF and that a comprehensive pulmonary hemodynamic evaluation may identify pulmonary vascular phenotypes that differentially predict HF phenotypes.

Effect of riociguat on pulmonary arterial compliance in the PATENT and CHEST studies.

Pulmonary arterial compliance is a measure of the pulsatile afterload of the right ventricle. Lower pulmonary arterial compliance is associated with reduced right ventricular function and worse prognosis in pulmonary hypertension. The effect of pulmonary vasodilators on pulmonary arterial compliance has not been evaluated in detail in pulmonary arterial hypertension or chronic thromboembolic pulmonary hypertension. In this post hoc analysis of patients with pulmonary arterial hypertension and chronic thromboembolic pulmonary hypertension in the PATENT and CHEST studies, we evaluated the change in pulmonary arterial compliance with riociguat versus placebo. Association of pulmonary arterial compliance with clinical outcomes was assessed using Kaplan–Meier and Cox proportional hazards analyses. Compared with placebo, riociguat significantly improved pulmonary arterial compliance in patients with pulmonary arterial hypertension or chronic thromboembolic pulmonary hypertension. Pulmonary arterial compliance at baseline was associated with survival and clinical worsening-free survival in pulmonary arterial hypertension but only with clinical worsening-free survival in chronic thromboembolic pulmonary hypertension. In patients with pulmonary arterial hypertension, pulmonary arterial compliance at follow-up ≥1.6 mL/mmHg was associated with better outcomes than pulmonary arterial compliance <1.6 mL/mmHg. In patients with chronic thromboembolic pulmonary hypertension, pulmonary arterial compliance at follow-up did not predict outcomes. Cox proportional hazards analyses showed no association between change in pulmonary arterial compliance and outcomes in patients with pulmonary arterial hypertension or chronic thromboembolic pulmonary hypertension. In conclusion, riociguat improved pulmonary arterial compliance in patients with pulmonary arterial hypertension or chronic thromboembolic pulmonary hypertension. Pulmonary arterial compliance at baseline or follow-up, rather than change in pulmonary arterial compliance, is of prognostic importance for outcomes.

Pulmonary and systemic hemodynamics are associated with myocardial injury in the acute respiratory distress syndrome.

BackgroundWhether right and left heart hemodynamics are associated with myocardial injury in the acute respiratory distress syndrome (ARDS) is not known.MethodsWe performed a retrospective cohort study of subjects who had right heart catheterization within the ALVEOLI trial and Fluid and Catheter Treatment Trial. Myocardial injury was assessed using a highly sensitive troponin assay (hsTn; Abbot ARCHITECT). Hemodynamic variables included right atrial pressure, pulmonary artery wedge pressure, cardiac index and stroke volume, pulmonary vascular resistance, pulmonary arterial compliance, and pulmonary effective arterial elastance. We performed linear, logistic, and Cox regression to determine the association of hemodynamic variables with myocardial injury and to determine if hemodynamics mediated the association between myocardial injury and death.ResultsAmong 252 ARDS patients, median day 0 troponin was 65.4 (13.8–397.8) ng/L. Lower cardiac index (β −0.23 SE 0.10; P < 0.001) and stroke volume (β −0.26 SE 0.005; P < 0.001), higher pulmonary vascular resistance (β 0.22 SE 0.11; P < 0.001), lower pulmonary arterial compliance (β −0.24 SE 0.06; P < 0.001), and higher arterial elastance (β 0.27 SE 0.43; P < 0.001) were associated with greater myocardial injury in univariable and adjusted models. Changes in stroke volume, cardiac index, pulmonary arterial compliance, pulmonary vascular resistance, and arterial elastance were all associated with progressive myocardial injury over three days. hsTn levels were associated with mortality; however, the association was attenuated after adjustment for each of stroke volume, pulmonary vascular resistance, pulmonary arterial compliance, and arterial elastance.ConclusionPulmonary vascular hemodynamics are associated with myocardial injury in ARDS, while filling pressures are not. Pulmonary vascular disease may represent a treatable contributor to myocardial injury in ARDS.

Age-related differences in hemodynamics and functional status in pulmonary arterial hypertension: Baseline results from the Pulmonary Hypertension Association Registry

The age of patients with pulmonary arterial hypertension (PAH) has increased, with registries now reporting mean ages of 50 to 65 years old. Limited data exist on age-related differences in hemodynamic and functional assessments in PAH. Adults with PAH in the Pulmonary Hypertension Association Registry were divided into 3 groups (18-50, 51-65, and >65 years old). Analysis of variance and chi-square testing were used to assess for baseline differences. Linear regression was used to examine the association of age with continuous hemodynamic and functional variables. A total of 769 patients with mean age of 56 ± 16 years were included. Older patients had more connective tissue disease-associated PAH and less drug-associated PAH. In linear regression models, each year of increased age was associated with shorter 6-minute walk distance (-3.37 meters; 95% CI, -3.97 to -2.76), lower mean pulmonary arterial pressure (-0.21 mmHg; 95% CI, -0.27 to -0.15), and lower pulmonary vascular resistance (-0.06 Wood units; 95% CI, -0.09 to -0.04). Pulmonary arterial compliance, cardiac index, right ventricular stroke work index, and percent predicted 6-minute walk distance were unrelated to age; resistance-compliance time was negatively related to age (-3 milliseconds per year; 95% CI, -4 to -2). Relative to their pulmonary vascular resistance, older patients have lower pulmonary artery compliance and worse right ventricular performance. Based on these findings, we suspect that age influences right ventricular loading conditions and the response of the right ventricle to increased afterload.

1414Vasodilator challenge with levosimendan as alternative to nitric oxide in advanced heart failure heart transplant candidates

Abstract Introduction Vasodilator challenge (VC) during right heart catheterization in heart transplant (HTx) candidates is warranted whenever pulmonary artery (PA) systolic pressure ≥50 mmHg and either transpulmonary gradient (TPG) ≥15 mmHg or pulmonary vascular resistance (PVR) &gt;3 WU as long as systolic arterial blood pressure &gt;85 mmHg. Nitric oxide (NO) remains the mainstay but in doubtful cases a 24–48h course of diuretics, inotropes and vasoactive agents may be required. Our aim is to report our centre's experience with levosimendan (LEVO) as alternative to NO in VC in HTx candidates due to advanced heart failure (HF). Methods VC records with either NO (20 ppm for 5–10 mins) or within 72h of LEVO infusion (12 mg/kg/min for 24–48h) carried out between 2009 and September 2018 were retrieved from the centre's database. Analysis was carried out with Fisher's exact test or Student's t-test for categorical and continuous variables, respectively, or the equivalent non-parametric test for non-normal distribution variables. Data are presented as counts and percentage, or mean ± standard deviation and median, percentile 25–75, for categorical and continuous variables, respectively. Results Baseline demographic and clinical characteristics from 26 patients (NO=13; LEVO=13) were similar between groups (12% female; 54±10 years of age; left ventricular ejection fraction 20±7%; BNP 1550±1090 pg/mL; 88% on NYHA III-IV). Although no differences were observed in baseline cardiac index (CI, 1.6±0.3 vs 1.4±0.4 L/min.m-2, in NO and LEVO, respectively), LEVO patients showed higher right ventricular systolic (70±10 vs 60±13 mmHg; p=0.036) and diastolic pressures (16±4 vs 11±5 mmHg; p=0.009) and lower PA compliance (0.9±0.2 vs 1.3±0.4 ml/mmHg; p=0.007) as well as a trend for increased PA wedge pressure (26±4 vs 21±4 mmHg; p=0.09), translating worse hemodynamics. Upon VC only LEVO decreased PA pressure and the increase in CI was higher compared with NO (2.5±0.8 vs 1.9±0.5 L/min.m-2, p=0.004) thus PVR reduction was comparable between groups (7.8±2.7 to 4.7±1.8 vs 6.3±2.3 to 3.6±2.1 WU, respectively). Also, only LEVO increased right (497, 387–837 to 791, 570–946 mmHg.mL.m-2; p=0.006) and left ventricular stroke work index (895, 807–1364 to 1257, 1107–2957 mmHg.mL.m-2; p=0.005) and cardiac power output (0.4±0.1 to 0.6±0.1 W; p&lt;0.001). Increase in PA compliance was also higher in LEVO (89±98 vs 22±30 Δ%, p=0.04). On the other hand, NO increased wedge pressure whereas LEVO had no effect thus TPG reduction was higher with NO (42±24% vs 17±27% drops, respectively; p=0.022). After HTx (NO=4; LEVO=10) mortality was similar in both groups (25% vs 30%; p=1.00). Conclusion LEVO is a safe and effective alternative in PVR reduction for VC. Its positive inotropic effect and long-lasting hemodynamic improvement may improve clinical status before HTx and allow better scrutiny of suitable candidates.

Right Ventricular-Arterial Uncoupling During Exercise in Heart Failure With Preserved Ejection Fraction: Role of Pulmonary Vascular Dysfunction

Right ventricular (RV) dysfunction is associated with shortened life expectancy in heart failure with preserved ejection fraction (HFpEF). The contribution of pulmonary vascular dysfunction to RV dysfunction in HFpEF is not well understood. We investigated rest and exercise invasive pulmonary hemodynamics, ventilation, and gas exchange in 67 patients with HFpEF (of whom 28 had an abnormal pulmonary vascular response during exercise referred to as HFpEF+PVR group and 39 had a normal pulmonary vascular response during exercise referred to as HFpEF group) and in 21 matched control subjects. Both groups of patients with HFpEF had a markedly decreased peak oxygen consumption (Vo2), decreased oxygen delivery, and impaired chronotropic response. Single beat analysis of RV pressure waveforms was used to compute the end-systolic elastance (Ees) and pulmonary arterial elastance (Ea). Right ventricular-pulmonary artery (RV-PA) coupling was measured as the ratio of Ees/Ea. Exercise was associated with a preserved Ees response but a decreased Ees/Ea in patients with HFpEF with a normal PVR response, indicating partially preserved RV contractile reserve. In HFpEF+PVR, exercise-induced increase in Ees was markedly reduced, resulting in decreased Ees/Ea and RV-PA uncoupling. Patients with HFpEF+PVR with an exercise-induced decrease in Ees/Ea had lower pulmonary artery compliance, lower peak Vo2, and lower stroke volume than patients with HFpEF. We conclude that RV-PA uncoupling is common in HFpEF and is caused by both intrinsic RV contractile impairment and afterload mismatch. Resting and dynamic RV-PA uncoupling in HFpEF is driven by an increase in RV pulsatile rather than resistive afterload. However, with the additive effects of increased RV resistive afterload, RV-PA uncoupling worsens dynamically during exercise.

Exercise unmasks distinct pathophysiologic features in heart failure with preserved ejection fraction and pulmonary vascular disease.

Pulmonary hypertension (PH) and pulmonary vascular disease (PVD) are common and associated with adverse outcomes in heart failure with preserved ejection fraction (HFpEF). Little is known about the impact of PVD on the pathophysiology of exercise intolerance. Heart failure with preserved ejection fraction patients (n = 161) with elevated pulmonary capillary wedge pressure (≥15 mmHg) at rest were classified into three groups: non-PH-HFpEF (n = 21); PH but no PVD (isolated post-capillary PH, IpcPH; n = 95); and PH with PVD (combined post- and pre-capillary PH, CpcPH; n = 45). At rest, CpcPH-HFpEF patients had more right ventricular (RV) dysfunction and lower pulmonary arterial (PA) compliance compared to all other groups. While right atrial pressure (RAP) and left ventricular transmural pressure (LVTMP) were similar in HFpEF with and without PH or PVD at rest, CpcPH-HFpEF patients demonstrated greater increase in RAP, enhanced ventricular interdependence, and paradoxical reduction in LVTMP during exercise, differing from all other groups (P < 0.05). Lower PA compliance was correlated with greater increase in RAP with exercise. During exercise, CpcPH-HFpEF patients displayed an inability to enhance cardiac output, reduction in forward stroke volume, and blunted augmentation in RV systolic performance, changes that were coupled with marked limitation in aerobic capacity. Heart failure with preserved ejection fraction patients with PVD demonstrate unique haemodynamic limitations during exercise that constrain aerobic capacity, including impaired recruitment of LV preload due to excessive right heart congestion and blunted RV systolic reserve. Interventions targeted to this distinct pathophysiology require testing in patients with HFpEF and PVD.

Acute Biventricular Mechanical Circulatory Support for Cardiogenic Shock.

BackgroundBiventricular failure is associated with high in‐hospital mortality. Limited data regarding the efficacy of biventricular Impella axial flow catheters (BiPella) support for biventricular failure exist. The aim of this study was to explore the clinical utility of percutaneously delivered BiPella as a novel acute mechanical support strategy for patients with cardiogenic shock complicated by biventricular failure.Methods and ResultsWe retrospectively analyzed data from 20 patients receiving BiPella for biventricular failure from 5 tertiary‐care hospitals in the United States. Left ventricular support was achieved with an Impella 5.0 (n=8), Impella CP (n=11), or Impella 2.5 (n=1). All patients received the Impella RP for right ventricular (RV) support. BiPella use was recorded in the setting of acute myocardial infarction (n=11), advanced heart failure (n=7), and myocarditis (n=2). Mean flows achieved were 3.4±1.2 and 3.5±0.5 for left ventricular and RV devices, respectively. Total in‐hospital mortality was 50%. No intraprocedural mortality was observed. Major complications included limb ischemia (n=1), hemolysis (n=6), and Thrombolysis in Myocardial Infarction major bleeding (n=7). Compared with nonsurvivors, survivors were younger, had a lower number of inotropes or vasopressors used before BiPella, and were more likely to have both devices implanted simultaneously during the same procedure. Compared with nonsurvivors, survivors had lower pulmonary artery pressures and RV stroke work index before BiPella. Indices of RV afterload were quantified for 14 subjects. Among these patients, nonsurvivors had higher pulmonary vascular resistance (6.8; 95% confidence interval [95% CI], 5.5–8.1 versus 1.9; 95% CI, 0.8–3.0; P<0.01), effective pulmonary artery elastance (1129; 95% CI, 876–1383 versus 458; 95% CI, 263–653; P<0.01), and lower pulmonary artery compliance (1.5; 95% CI, 0.9–2.1 versus 2.7; 95% CI, 1.8–3.6; P<0.05).ConclusionsThis is the largest, retrospective analysis of BiPella for cardiogenic shock. BiPella is feasible, reduces cardiac filling pressures and improves cardiac output across a range of causes for cardiogenic shock. Simultaneous left ventricular and RV device implantation and lower RV afterload may be associated with better outcomes with BiPella. Future prospective studies of BiPella for cardiogenic shock are required.

Hemodynamic Phenotyping of Pulmonary Hypertension in Left Heart Failure.

Increased pulmonary venous pressure secondary to left heart disease is the most common cause of pulmonary hypertension (PH). The diagnosis of PH due to left heart disease relies on a clinical probability assessment followed by the invasive measurements of a mean pulmonary artery pressure (PAP) ≥25 mm Hg and mean wedged PAP (PAWP) >15 mm Hg. A combination of mean PAP and mean PAWP defines postcapillary PH. Postcapillary PH is generally associated with a diastolic pulmonary pressure gradient (diastolic PAP minus mean PAWP) <7 mm Hg, a transpulmonary pressure gradient (mean PAP minus mean PAWP) <12 mm Hg, and pulmonary vascular resistance ≤3 Wood units (WU). This combination of criteria defines isolated postcapillary PH. Postcapillary PH with elevated vascular gradients and pulmonary vascular resistance defines combined post- and precapillary PH (Cpc-PH). Postcapillary PH is associated with a decreased survival in proportion to increased pulmonary vascular gradients, decreased pulmonary arterial compliance, and reduced right ventricular function. The Cpc-PH subcategory occurs in 12% to 13% of patients with PH due to left heart disease. Patients with Cpc-PH have severe PH, with higher diastolic pulmonary pressure gradient, transpulmonary pressure gradient, and pulmonary vascular resistance and more pronounced ventilatory responses to exercise, lower pulmonary arterial compliance, depressed right ventricular ejection fraction, and shorter life expectancy than isolated postcapillary PH. Cpc-PH bears similarities to pulmonary arterial hypertension. Whether Cpc-PH is amenable to therapies targeting the pulmonary circulation remains to be tested by properly designed randomized controlled trials.

Changes in main pulmonary artery diameter during follow-up have prognostic implications in pulmonary arterial hypertension.

A dilated pulmonary artery (PA) is a common finding in patients with pulmonary arterial hypertension (PAH). Little is known on the variations in PA size over time and whether these changes track with disease severity and/or predict long-term survival. We included patients with PAH who had at least two computed tomography (CT) scans of the chest done on different visits. Both scans matched the use of i.v. contrast. Pairs of CT scans were compared in 113 PAH patients. During a median (interquartile range (IQR)) time difference between scans of 8 (IQR: 3.5-20.0) months, we noted an increase in main PA diameter of 0.5 ± 1.8 mm (mean ± SD) (P = 0.008). When CT scans were performed >12 months apart (n = 47), the main PA diameter increased or decreased by >1 mm in 40% and 13% of the patients, respectively. An increase in main PA diameter was associated with lower PA compliance, higher right ventricular (RV) systolic pressure, worse RV function and a decline in 6-min walk distance. During a median (IQR) follow-up of 33 (IQR: 4.5-47) months, 53 (46.9%) patients died. The change in PA diameter was a significant predictor of mortality (hazard ratio (HR) per mm increase: 1.33 (95% CI: 1.11-1.61), P = 0.002) when adjusted for difference in time and slice thickness between CT scans, age, gender, PAH aetiology and pulmonary vascular resistance. In PAH patients, an increase in CT-derived main PA diameter over time is associated with progression in pulmonary pressures, RV dysfunction, a decline in functional capacity and higher mortality.

RV Contractile Function and its Coupling to Pulmonary Circulation in Heart Failure With Preserved Ejection Fraction: Stratification of Clinical Phenotypes and Outcomes

ObjectivesThis study sought to investigate how right ventricular (RV) contractile function and its coupling with pulmonary circulation (PC) stratify clinical phenotypes and outcome in heart failure preserved ejection fraction (HFpEF) patients. BackgroundPulmonary hypertension and RV dysfunction are key hemodynamic abnormalities in HFpEF. MethodsThree hundred eighty seven HFpEF patients (mean age 64 ± 12 years, 59% females, left ventricular ejection fraction 59 ± 7%) underwent RV and pulmonary hemodynamic evaluation by echocardiography (entire population) and right heart catheterization (219 patients). Patients were investigated by tricuspid annular plane systolic excursion (TAPSE) to pulmonary artery systolic pressure (PASP) relationship and stratified according to TAPSE/PASP ratio tertiles (1: <0.35; 2: 0.35 to 0.57; 3: >0.57). Specifically, TAPSE/PASP ratio was taken as a noninvasive index of RV to PC coupling based on the correlation with invasively evaluated RV systolic elastance/arterial elastance (r = 0.35; p < 0.0001). ResultsGroups had similar prevalence of comorbidities except for a higher prevalence of atrial fibrillation and kidney dysfunction in tertile 1. Progressively increasing levels of natriuretic peptides, worse systemic and pulmonary hemodynamics, abnormal exercise aerobic capacity and ventilatory inefficiency were observed from the highest to lowest TAPSE/PASP tertile. TASPE/PASP correlated with pulmonary artery compliance (r = 0.69; p < 0.0001). Remarkably, the tertile 1 group distributed along the worse portion of the curve at lower pulmonary artery compliance and higher pulmonary vascular resistances. In addition, the TAPSE/PASP ratio emerged as an independent predictor of worse outcomes. ConclusionsA thorough assessment of RV-PC coupling and RV contractile function stratify HFpEF phenotypes at different level of risk. These observations shift the interest toward therapeutic strategies that may benefit the right heart as primary unmet need in the complex pathophysiology of the HFpEF syndrome.

Development of a servo pump system for in vivo loading of pathological pulmonary artery impedance on the right ventricle of normal rats.

Pulmonary artery (PA) impedance provides detailed information on right ventricular (RV) afterload in pulmonary hypertension (PH). This study aimed to examine PA impedance in a rat model of monocrotaline-induced PH (MCT-PH) and to develop an experimental system for in vivo loading of pathological PA impedance on the RV of normal rats. PA impedance was quantified in normal (n= 10) and MCT-PH rats (n= 10) using a three-element Windkessel (3-WK) model. Compared with normal rats, MCT-PH rats had higher characteristic impedance (ZC) and peripheral pulmonary resistance (RP) (ZC: 0.121 ± 0.039 vs. 0.053 ± 0.017 mmHg·min·ml(-1), P< 0.001; RP: 0.581 ± 0.334 vs. 0.252 ± 0.105 mmHg·min·ml(-1), P= 0.013) and lower pulmonary artery compliance (CP) (0.242 ± 0.131 vs. 0.700 ± 0.186 ml/mmHg, P< 0.001). In another group of 10 normal rats, a computer-controlled servo pump was connected to the left PA for loading PA impedance with parameters in pathological ranges designed by the 3-WK model. Activation of the servo pump decreased the error of measured vs. target PA impedance (modulus: from 0.047 ± 0.020 without pump activation to 0.019 ± 0.007 with pump activation,P< 0.001; phase: 0.085 ± 0.028 to 0.043 ± 0.012 radians,P< 0.001). In conclusion, MCT-PH increases ZC and RP and decreases CP Our servo pump system, which is capable of imposing arbitrary PA impedance with pathological parameters, may offer a unique opportunity to delineate the pathological significance of PA impedance in PH.

Lung congestion in chronic heart failure: haemodynamic, clinical, and prognostic implications.

The goal of the study was to examine the prognostic impact, haemodynamic and clinical features associated with lung congestion in patients with chronic heart failure (HF). HF patients (n = 186) and HF-free controls (n = 21) underwent right heart catheterization, echocardiography, pulmonary function testing and chest radiography that was blindly scored for the presence and severity of lung oedema. Lung congestion correlated directly with pulmonary vascular resistance (PVR, P = 0.004) and inversely with pulmonary artery (PA) compliance (P < 0.001) and the diffusion limit for carbon monoxide (DLCO , P = 0.009). Compared with dry lung HF, wet lung HF patients (congestion score > median) had 25% lower PA compliance and 25-35% higher PVR, transpulmonary gradients and PA pressures (40 vs. 32 mmHg, P < 0.001) despite marginally higher PA wedge pressure (PAWP; 22 vs. 19 mmHg, P = 0.002). Wet lung HF patients displayed more right ventricular (RV) dilatation and dysfunction, more restrictive ventilation and greater reduction of DLCO . The strongest correlates of lung congestion were NT-proBNP, haemoglobin, albumin, and glomerular filtration, all surpassing PAWP. After a median of 333 days (interquartile range 80-875), 59 patients (32%) died. Lung congestion was associated with reduced survival (P < 0.0001), even after adjusting for PAWP, NT-proBNP, anaemia, CAD and renal dysfunction. Interstitial lung oedema is associated with pulmonary vascular disease, RV overload and dysfunction and increased mortality in HF. These data reinforce the importance of aggressive decongestion in HF and suggest that novel agents aimed at reducing lung water may help to deter progression of pulmonary vascular disease and biventricular HF.