Peter J. Leary

The diastolic pulmonary gradient does not predict survival in patients with pulmonary hypertension due to left heart disease.

OBJECTIVES This study sought to evaluate if diastolic pulmonary gradient (DPG) can predict survival in patients with pulmonary hypertension due to left heart disease (PH-LHD). BACKGROUND Patients with combined post- and pre-capillary PH-LHD have worse prognosis than those with passive pulmonary hypertension. The transpulmonary gradient (TPG) and pulmonary vascular resistance (PVR) have commonly been used to identify high-risk patients. However, these parameters have significant shortcomings and do not always correlate with pulmonary vasculature remodeling. Recently, it has been suggested that DPG may be better a marker, yet its prognostic ability in patients with cardiomyopathy has not been fully assessed. METHODS A retrospective cohort of 1,236 patients evaluated for unexplained cardiomyopathy at Johns Hopkins Hospital was studied. All patients underwent right heart catheterization and were followed until death, cardiac transplantation, or the end of the study period (mean time 4.4 years). The relationships between DPG, TPG, or PVR and survival in subjects with PH-LHD (n = 469) were evaluated with Cox proportional hazards regression and Kaplan-Meier analyses. RESULTS DPG was not significantly associated with mortality (hazard ratio [HR]: 1.02, p = 0.10) in PH-LHD whereas elevated TPG and PVR predicted death (HR: 1.02, p = 0.046; and HR: 1.11, p = 0.002, respectively). Similarly, DPG did not differentiate survivors from non-survivors at any selected cut points including a DPG of 7 mm Hg. CONCLUSIONS In this retrospective study of patients with cardiomyopathy and PH-LHD, an elevated DPG was not associated with worse survival.

Prognostic value of the pre-transplant diastolic pulmonary artery pressure–to–pulmonary capillary wedge pressure gradient in cardiac transplant recipients with pulmonary hypertension

BACKGROUND Although the transpulmonary gradient (TPG) and pulmonary vascular resistance (PVR) are commonly used to differentiate heart failure patients with pulmonary vascular disease from those with passive pulmonary hypertension (PH), elevations in TPG and PVR may not always reflect pre-capillary PH. Recently, it has been suggested an elevated diastolic pulmonary artery pressure-to-pulmonary capillary wedge pressure gradient (DPG) may be a better indicator of pulmonary vascular remodeling, and therefore, may be of added prognostic value in patients with PH being considered for cardiac transplantation. METHODS Using the United Network for Organ Sharing (UNOS) database, we retrospectively reviewed all primary adult (age > 17 years) orthotropic heart transplant recipients between 1998 and 2011. All patients with available pre-transplant hemodynamic data and PH (mean pulmonary artery pressure ≥ 25 mm Hg) were included (n = 16,811). We assessed the prognostic value of DPG on post-transplant survival in patients with PH and an elevated TPG and PVR. RESULTS In patients with PH and a TPG > 12 mm Hg (n = 5,827), there was no difference in survival at up to 5 years post-transplant between high DPG (defined as ≥3, ≥5, ≥7, or ≥10 mm Hg) and low DPG (<3, <5, <7, or <10 mm Hg) groups. Similarly, there was no difference in survival between high and low DPG groups in those with a PVR > 3 Wood units (n = 6,270). Defining an elevated TPG as > 15 mm Hg (n = 3,065) or an elevated PVR > 5 (n = 1,783) yielded similar results. CONCLUSIONS This large analysis investigating the prognostic value of DPG found an elevated DPG had no effect on post-transplant survival in patients with PH and an elevated TPG and PVR.

Three-dimensional analysis of right ventricular shape and function in pulmonary hypertension

Right ventricular (RV) failure is a key determinant of morbidity and mortality in pulmonary hypertension (PH). The present study aims to add to existing descriptions of RV structural and functional changes in PH through a comprehensive three-dimensional (3D) shape analysis. We performed 3D echocardiography on 53 subjects with PH and 19 normal subjects. Twenty short-axis slices from apex to tricuspid centroid were measured to characterize regional shape: apical angle, basal bulge, eccentricity, and area. Transverse shortening was assessed by fractional area change (FAC) in each short-axis slice, longitudinal contraction was assessed by tricuspid annular plane systolic excursion (TAPSE) and global function by RV ejection fraction. Multivariate logistic analysis was used to compare the association of RV parameters with New York Heart Association (NYHA) class. Compared to normal, RV function in PH is characterized by decreased stroke volume index (SVi), fractional area change and ejection fraction. Increased eccentricity, apical rounding and bulging at the base characterize the shape of the RV in PH. Increased SVi, ejection fraction and mid-ventricular FAC were associated with less severe NYHA class in adjusted analyses. The RV in idiopathic PH (iPAH) was observed to have a larger end-diastolic volume and decreased function compared with connective tissue disease associated PH (ctd-PH). This work describes increased eccentricity and decreased systolic function in subjects with PH. Functional parameters were associated with NYHA class and heterogeneity in the phenotype was noted between subjects with iPAH and ctd-PH.

Traffic-related Air Pollution and the Right Ventricle. The Multi-ethnic Study of Atherosclerosis

RATIONALE Right heart failure is a cause of morbidity and mortality in common and rare heart and lung diseases. Exposure to traffic-related air pollution is linked to left ventricular hypertrophy, heart failure, and death. Relationships between traffic-related air pollution and right ventricular (RV) structure and function have not been studied. OBJECTIVES To characterize the relationship between traffic-related air pollutants and RV structure and function. METHODS We included men and women with magnetic resonance imaging assessment of RV structure and function and estimated residential outdoor nitrogen dioxide (NO2) concentrations from the Multi-ethnic Study of Atherosclerosis, a study of individuals free of clinical cardiovascular disease at baseline. Multivariable linear regression estimated associations between NO2 exposure (averaged over the year prior to magnetic resonance imaging) and measures of RV structure and function after adjusting for demographics, anthropometrics, smoking status, diabetes mellitus, and hypertension. Adjustment for corresponding left ventricular parameters, traffic-related noise, markers of inflammation, and lung disease were considered in separate models. Secondary analyses considered oxides of nitrogen (NOx) as the exposure. MEASUREMENTS AND MAIN RESULTS The study sample included 3,896 participants. In fully adjusted models, higher NO2 was associated with greater RV mass and larger RV end-diastolic volume with or without further adjustment for corresponding left ventricular parameters, traffic-related noise, inflammatory markers, or lung disease (all P < 0.05). There was no association between NO2 and RV ejection fraction. Relationships between NOx and RV morphology were similar. CONCLUSIONS Higher levels of NO2 exposure were associated with greater RV mass and larger RV end-diastolic volume.

Protocol for exercise hemodynamic assessment: performing an invasive cardiopulmonary exercise test in clinical practice.

Invasive cardiopulmonary exercise testing (iCPET) combines full central hemodynamic assessment with continuous measurements of pulmonary gas exchange and ventilation to help in understanding the pathophysiology underpinning unexplained exertional intolerance. There is increasing evidence to support the use of iCPET as a key methodology for diagnosing heart failure with preserved ejection fraction and exercise-induced pulmonary hypertension as occult causes of exercise limitation, but there is little information available outlining the methodology to use this diagnostic test in clinical practice. To bridge this knowledge gap, the operational protocol for iCPET at our institution is discussed in detail. In turn, a standardized iCPET protocol may provide a common framework to describe the evolving understanding of mechanism(s) that limit exercise capacity and to facilitate research efforts to define novel treatments in these patients.

Right ventricular afterload sensitivity dramatically increases after left ventricular assist device implantation: A multi-center hemodynamic analysis

BACKGROUND Right ventricular (RV) failure is a source of morbidity and mortality after left ventricular assist device (LVAD) implantation. In this study we sought to define hemodynamic changes in afterload and RV adaptation to afterload both early after implantation and with prolonged LVAD support. METHODS We reviewed right heart catheterization (RHC) data from participants who underwent continuous-flow LVAD implantation at our institutions (n = 244), excluding those on inotropic or vasopressor agents, pulmonary vasodilators or additional mechanical support at any RHC assessment. Hemodynamic data were assessed at 5 time intervals: (1) pre-LVAD (within 6 months); (2) early post-LVAD (0 to 6 months); (3) 7 to 12 months; (4) 13 to 18 months; and (5) very late post-LVAD (18 to 36 months). RESULTS Sixty participants met the inclusion criteria. All measures of right ventricular load (effective arterial elastance, pulmonary vascular compliance and pulmonary vascular resistance) improved between the pre- and early post-LVAD time periods. Despite decreasing load and pulmonary artery wedge pressure (PAWP), RAP remained unchanged and the RAP:PAWP ratio worsened early post-LVAD (0.44 [0.38, 0.63] vs 0.77 [0.59, 1.0], p < 0.001), suggesting a worsening of RV adaptation to load. With continued LVAD support, both RV load and RAP:PAWP decreased in a steep, linear and dependent manner. CONCLUSIONS Despite reducing RV load, LVAD implantation leads to worsened RV adaptation. With continued LVAD support, both RV afterload and RV adaptation improve, and their relationship remains constant over time post-LVAD. These findings suggest the RV afterload sensitivity increases after LVAD implantation, which has major clinical implications for patients struggling with RV failure.

Volume Overload: Prevalence, Risk Factors, and Functional Outcome in Survivors of Septic Shock

RATIONALE Survivors of septic shock have impaired functional status. Volume overload is associated with poor outcomes in patients with septic shock, but the impact of volume overload on functional outcome and discharge destination of survivors is unknown. OBJECTIVES This study describes patterns of fluid management both during and after septic shock. We examined factors associated with volume overload upon intensive care unit (ICU) discharge. We then examined associations between volume overload upon ICU discharge, mobility limitation, and discharge to a healthcare facility in septic shock survivors, with the hypothesis that volume overload is associated with increased odds of these outcomes. METHODS We retrospectively reviewed the medical records of 247 patients admitted with septic shock to an academic county hospital between June 2009 and April 2012 who survived to ICU discharge. We defined volume overload as a fluid balance expected to increase the subjects admission weight by 10%. Statistical methods included unadjusted analyses and multivariable logistic regression. MEASUREMENTS AND MAIN RESULTS Eighty-six percent of patients had a positive fluid balance, and 35% had volume overload upon ICU discharge. Factors associated with volume overload in unadjusted analyses included more severe illness, cirrhosis, blood transfusion during shock, and higher volumes of fluid administration both during and after shock. Blood transfusion during shock was independently associated with increased odds of volume overload (odds ratio [OR], 2.65; 95% confidence interval [CI], 1.33-5.27; P = 0.01) after adjusting for preexisting conditions and severity of illness. Only 42% of patients received at least one dose of a diuretic during their hospitalization. Volume overload upon ICU discharge was independently associated with inability to ambulate upon hospital discharge (OR, 2.29; 95% CI, 1.24-4.25; P = 0.01) and, in patients admitted from home, upon discharge to a healthcare facility (OR, 2.34; 95% CI, 1.1-4.98; P = 0.03). CONCLUSIONS Volume overload is independently associated with impaired mobility and discharge to a healthcare facility in survivors of septic shock. Prevention and treatment of volume overload in patients with septic shock warrants further investigation.

Maternal, perinatal, and postneonatal outcomes in women with chronic heart disease in Washington State.

OBJECTIVE: To explore the association between the presence of maternal heart disease and maternal, perinatal, and infant outcomes. METHODS: We conducted a population-based retrospective cohort study using Washington State birth certificates linked with hospital discharge records of mothers noted to have maternal congenital heart disease, ischemic heart disease, heart failure, or pulmonary hypertension. Women who gave birth between 1987 and 2009 (n=2,171) were compared with a sample of mothers without these conditions (n=21,710). We described characteristics of pregnant women with heart disease over time. Logistic regression estimated the association between chronic maternal heart disease and small-for-gestational-age (SGA) neonates as well as perinatal, postneonatal, and maternal death. RESULTS: The proportion of births to women with reported heart disease increased 224% between the 1987 and 1994 and 2002 and 2009 calendar periods. Chronic maternal heart disease was associated with increased risk of SGA (62 additional SGA newborns per 1,000 births, 95% confidence interval [CI] 46–78; P<.001), perinatal death (14 additional deaths per 1,000 births, 95% CI 8–20; P<.001), postneonatal death (5 additional deaths per 1,000 births, 95% CI 2–9; P<.001), and maternal death (5 additional deaths per 1,000 births, 95% CI 2–9; P<.001). CONCLUSION: The presence of chronic maternal heart disease is associated with elevated risk for poor maternal, perinatal, and postneonatal outcomes. LEVEL OF EVIDENCE: II

Pulmonary Arterial Compliance Improves Rapidly after Left Ventricular Assist Device Implantation

Pulmonary artery compliance (PAC) contributes to right ventricular (RV) afterload, is decreased in the setting of increased left ventricular (LV) filling pressures, and may be an important component of World Health Organization (WHO) group II pulmonary hypertension (PH). Left ventricular assist device (LVAD) implantation can rapidly change LV filling, but its relationship with PAC is unknown. Right heart catheterization was performed preoperatively, postoperatively (between 48 and 72 hours), and >30 days post-LVAD implantation in a cohort of 64 patients with end-stage systolic heart failure. Within 72 hours, LVAD implantation was associated with an increase in PAC (2.0—3.7 ml/mm Hg, p < 0.0001), a decrease in pulmonary vascular resistance (3.5—1.7 Wood units, p < 0.0001). Pulmonary arterial compliance did not increase further at the >30 post-LVAD time point (3.7 ± 1.7 to 3.6 ± 0.44 ml/mm Hg, p = 0.44). Pulmonary artery compliance improves rapidly after LVAD implantation. This suggests that more permanent changes in the pulmonary vascular bed may not be responsible for the abnormal PAC observed in WHO group II PH.

Pulmonary Hypertension in Congenital Heart Disease: Beyond Eisenmenger Syndrome.

Patients with adult congenital heart disease have an increased risk of developing pulmonary hypertension. There are several mechanisms of pulmonary hypertension in patients with adult congenital heart disease, and understanding them requires a systematic approach to define the patients hemodynamics and physiology. This article reviews the updated classification of pulmonary hypertension in patients with adult congenital heart disease with a focus on pathophysiology, diagnostics, and the evaluation of pulmonary hypertension in special adult congenital heart disease populations.