Refined Balloon Pulmonary Angioplasty in Chronic Thromboembolic Pulmonary Hypertension: Initial Results of U.S. Regional Program.

Objectives: We sought to evaluate the efficacy and safety of refined balloon pulmonary angioplasty (BPA) in the treatment of patients with chronic thromboembolic pulmonary hypertension (CTEPH). Background: BPA is rapidly evolving therapeutic option for patients with nonsurgical CTEPH. There are few US studies that have reported on the outcomes of this novel therapeutic option. Methods: This is a retrospective study of CTEPH patients that underwent BPA at Temple University Hospital. The primary efficacy endpoint was the change in pulmonary vascular resistance (PVR) after BPA as compared to baseline and the primary safety endpoint was the rate of hemoptysis within 24 hours. Secondary endpoints included death, WHO functional class, and 6-minute walk distance (6MWD). We used logistic regression to evaluate factors associated with a hemodynamic and functional response. Results: A total of 211 BPA sessions were performed on 77 patients (average 2.7 ± 1.7 sessions/patient). After BPA the mean PVR improved by 26% (P<0.001) while the mean 6MWD improved by 71.7 meters (P <0.001) and WHO functional class improved by one functional class (P <0.001). Ten sessions (4.7%) were complicated by hemoptysis. The independent factors associated with a improved functional and hemodynamic response included the pre-procedural use of riociguat, reduce baseline PA compliance and > 3 BPA sessions per patient. Conclusion: This single center study from the US showed that BPA with refined techniques in patients with CTEPH was safe and was associated with significant improvements in pulmonary hemodynamics and functional capacity.

Initial Right Ventricular Dysfunction Severity Identifies Severe Peripartum Cardiomyopathy Phenotype With Worse Early and Overall Outcomes: A 24-Year Cohort Study.

BACKGROUND: Outcomes in peripartum cardiomyopathy (PPCM) vary. We sought to determine whether severity of left or right ventricular dysfunction (RVD) at PPCM diagnosis differentially associates with adverse outcomes. METHODS AND RESULTS: We conducted a single-center retrospective cohort study of 53 patients with PPCM. The primary outcome was a composite of left ventricular assist device implantation, cardiac transplantation, or death. We used Kaplan-Meier curves to examine event-free survival and Cox proportional hazards models to examine associations of left ventricular (LV) ejection fraction <30%, LV end-diastolic diameter ≥60 mm, and moderate-to-severe RVD at PPCM diagnosis with the primary outcome. Median (interquartile range) follow-up time was 3.6 (1.4-7.3) years. Seventeen patients (32%) experienced the primary outcome, of whom 11 had moderate-to-severe RVD at time of PPCM diagnosis. Overall event-free survival differed by initial RVD severity and LV ejection fraction <30%, but not by LV end-diastolic diameter ≥60 mm. In univariable analyses, LV ejection fraction <30% and moderate-to-severe RVD were associated with the outcome (hazard ratios [95% confidence intervals] of 4.85 [1.11-21.3] and 4.26 [1.47-11.6], respectively). In a multivariable model with LV ejection fraction <30%, LV end-diastolic diameter ≥60 mm, and moderate-to-severe RVD, only moderate-to-severe RVD was independently associated with the outcome (hazard ratio [95% confidence interval], 3.21 [1.13-9.10]). Although most outcomes occurred within the first year, nearly a third occurred years after PPCM diagnosis. CONCLUSIONS: Initial moderate-to-severe RVD is associated with a more advanced cardiomyopathy phenotype and increased risk of adverse outcomes in PPCM, within and beyond the first year of diagnosis. By identifying a worse PPCM phenotype, initial moderate-to-severe RVD may prompt earlier consideration of advanced heart replacement therapies.

Methods for Evaluating Right Ventricular Function and Ventricular-Arterial Coupling.

Right ventricular function (RVF) carries great prognostic significance in heart failure and pulmonary hypertension (PH). Although there is considerable focus on RVF in pulmonary arterial hypertension, RVF is also of great importance in group 2 PH. This article will discuss assessment of RVF and evaluation of the Right Ventricle-Pulmonary Artery (RV-PA) coupling relationship. Cardiac imaging modalities allow direct visualization and assessment of RVF. Imaging modalities include the commonly utilized echo-Doppler imaging evaluating RV fractional area change, tricuspid annular plane systolic excursion and Tissue Doppler Imaging, in addition to the increasingly utilized cardiac magnetic resonance. Invasive hemodynamic assessment also plays an important role and can also be employed during exercise to help elucidate functional reserve. Cardiopulmonary exercise testing provides added insight into the mechanisms of cardiopulmonary disease. Cardiac imaging, invasive hemodynamics, and gas exchange stress testing can be combined to give a more sophisticated understanding of RVF. The RV-PA coupling relationship can be assessed using practical and clinically available metrics in order to gain clinically relevant understanding of the patients' physiologic state. RV-PA coupling assessments can be done using invasive, combined noninvasive-invasive, or non-invasive approaches. We also discuss our approaches in the assessment of the RV-PA coupling relationship.

Echocardiographic and hemodynamic predictors of mortality in idiopathic pulmonary fibrosis.

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) can lead to the development of pulmonary hypertension, which is associated with an increased risk of death. In pulmonary arterial hypertension, survival is directly related to the capacity of the right ventricle to adapt to elevated pulmonary vascular load. The relative importance of right ventricular function in IPF is not well understood. Our objective was to evaluate right ventricular echocardiographic and hemodynamic predictors of mortality in a cohort of patients with IPF referred for lung transplant evaluation. METHODS: We performed a retrospective cohort study of 135 patients who met 2011 American Thoracic Society/European Respiratory Society criteria for IPF and who were evaluated for lung transplantation at the Hospital of the University of Pennsylvania. RESULTS: Right ventricle:left ventricle diameter ratio (hazard ratio [HR], 4.5; 95% CI, 1.7-11.9), moderate to severe right atrial and right ventricular dilation (HR, 2.9; 95% CI, 1.4-5.9; and HR, 2.7; 95% CI, 1.4-5.4, respectively) and right ventricular dysfunction (HR, 5.5; 95% CI, 2.6-11.5) were associated with an increased risk of death. Higher pulmonary vascular resistance was also associated with increased mortality (HR per 1 Wood unit, 1.3; 95% CI, 1.1-1.5). These risk factors were independent of age, sex, race, height, weight, FVC, and lung transplantation status. Other hemodynamic indices, such as mean pulmonary artery pressure and cardiac index, were not associated with outcome. CONCLUSIONS: Right-sided heart size and right ventricular dysfunction measured by echocardiography and higher pulmonary vascular resistance by invasive hemodynamic assessment predict mortality in patients with IPF evaluated for lung transplantation.

Ventilatory inefficiency reflects right ventricular dysfunction in systolic heart failure.

BACKGROUND: An increased minute ventilation (VE)/carbon dioxide production (VCO2) relationship, an expression of ventilatory inefficiency (VI), is associated with increased morbidity and mortality in patients with left ventricular systolic dysfunction (LVSD). A direct link between VI and a specific cardiac abnormality has not been established. METHODS: We analyzed cardiopulmonary exercise test (CPET) data from patients (N=83) with severe LVSD (ischemic and nonischemic; left ventricular ejection fraction [LVEF] 19%±7%) and at least moderate exercise intolerance. Subjects were stratified into two groups based on the (VE/VCO2 ratio at anaerobic threshold (VE/VCO2@AT) (group 1 VE/VCO2@AT≤34; group 2 VE/VCO2@AT>34). Clinical, CPET, echocardiographic, and hemodynamic data were compared between groups. RESULTS: Group 2 subjects had lower exercise capacity (peak (VO2, 45.7%±11.8% vs 50.4±8.9% predicted; P<.05), with a significantly lower oxygen pulse (71.6%±24.5% vs 85.4±18.5% predicted) and maximum systolic BP (122±19 mm Hg vs 138±22 mm Hg; P<.001 for both), suggesting a more blunted stroke volume to exercise vs group 1. There were no differences in left ventricular (LV) size, LVEF, or mitral regurgitation between the two groups. In sharp contrast, group 2 had larger right ventricular (RV) dimensions (4.5±1.1 cm vs 3.9±0.8 cm) and more severe RV systolic dysfunction (RV fractional area change 26%±11% vs 33%±12%; tricuspid annular plane systolic excursion [TAPSE] 1.6±0.5 cm vs 2.0±0.5 cm; all P<.001) vs group 1. Multivariable analysis revealed that only TAPSE and Doppler-estimated pulmonary artery systolic pressure were independently associated with VE/VCO2@AT and the (VE/VCO2slope. The VE/VCO2@AT, VE/VCO2 slope, and TAPSE had nearly identical predictive value for death or transplant. CONCLUSIONS: The present study suggests that VI is a functional, noninvasive marker of more advanced right-sided heart dysfunction in patients with severe LVSD.

Longitudinal shortening accounts for the majority of right ventricular contraction and improves after pulmonary vasodilator therapy in normal subjects and patients with pulmonary arterial hypertension.

BACKGROUND: The right ventricle has a unique contraction pattern, with a greater portion of the shortening occurring in the longitudinal plane. However, the relative contributions of longitudinal and transverse shortening to overall right ventricular (RV) function have not been quantified. We sought to quantify the proportions of longitudinal and transverse shortening to RV function in normal subjects and in patients with pulmonary arterial hypertension (PAH) at baseline and following PAH-specific therapy. METHODS: The normal cohort comprised 90 subjects with normal clinical echocardiograms, whereas the PAH cohort included 36 patients, of whom 25 had echocardiograms before and after initiation of PAH-specific therapy. Assessment of RV function included tricuspid annular plane systolic excursion, RV fractional area change (RVFAC), and relative change in RV area in longitudinal and transverse planes. RESULTS: Longitudinal fractional area change (LFAC) accounted for the majority of total RVFAC (77% ± 14%) in normal subjects. Among patients with PAH, longitudinal shortening still represented the majority of RVFAC, even though it was less than in normal subjects (63% ± 18%, P < .0001). Following PAH therapy, overall RV function improved (RVFAC, 30% ± 13% to 36% ± 9%; P = .026), solely because of an increase in longitudinal area change. As a result, the proportion of longitudinal shortening increased (LFAC, 58% ± 18% to 69% ± 17%; P = .002), whereas transverse shortening fell (transverse fractional area change, 42% ± 18% vs 31% ± 17%; P = .002). CONCLUSIONS: Longitudinal shortening accounts for the majority of RV contraction in normal subjects and patients with PAH, although less so in PAH. Improved RV function following pulmonary vasodilator therapy occurs solely from improvements in longitudinal contraction, suggesting that longitudinal shortening may represent the afterload-responsive element of RV functional recovery.