Group 3 Pulmonary Hypertension: From Bench to Bedside.

Pulmonary hypertension (PH) because of chronic lung disease is categorized as Group 3 PH in the most recent classification system. Prevalence of these diseases is increasing over time, creating a growing need for effective therapeutic options. Recent approval of the first pulmonary arterial hypertension therapy for the treatment of Group 3 PH related to interstitial lung disease represents an encouraging advancement. This review focuses on molecular mechanisms contributing to pulmonary vasculopathy in chronic hypoxia, the pathology and epidemiology of Group 3 PH, the right ventricular dysfunction observed in this population and clinical trial data that inform the use of pulmonary vasodilators in Group 3 PH.

Prognostic Implications of Right Ventricular Remodeling and Function in Patients With Significant Secondary Tricuspid Regurgitation.

BACKGROUND: In patients with significant (moderate and severe) tricuspid regurgitation (TR), the decision to intervene is influenced by right ventricular (RV) size and function. RV remodeling in significant secondary TR has been underexplored. The aim of this study was to characterize RV remodeling in patients with significant secondary TR and to investigate its prognostic implications. METHODS: RV remodeling was characterized by transthoracic echocardiography in 1292 patients with significant secondary TR (median age 71 [62-78]; 50% male). Four patterns of RV remodeling were defined according to the presence of RV dilation (tricuspid annulus≥40 mm) and RV systolic dysfunction (tricuspid annulus systolic excursion plane<17 mm): pattern 1, normal RV size and systolic function; pattern 2, dilated RV with preserved systolic function; pattern 3, normal RV size with systolic dysfunction; and pattern 4, dilated RV systolic dysfunction. The primary end point was all-cause mortality and the event rates were compared across the 4 patterns of RV remodeling. RESULTS: A total of 183 (14%) patients showed pattern 1 RV remodeling; 256 (20%) showed pattern 2; 304 (24%) presented with pattern 3; and 549 (43%) had pattern 4 RV remodeling. Patients with pattern 4 RV remodeling were more frequently male; more often had coronary artery disease, worse renal function, and impaired left ventricular ejection fraction; and were more often symptomatic. Only 98 (8%) patients underwent tricuspid valve annuloplasty during follow-up. During a median follow-up of 34 (interquartile range, 0-60) months, 510 (40%) patients died. The 5-year survival rate was significantly worse in patients presenting with patterns 3 and 4 RV remodeling in comparison with pattern 1 (52% and 49% versus 70%; P=0.002 and P<0.001, respectively), and were independently associated with poor outcome on multivariable analysis. CONCLUSIONS: In patients with significant secondary TR, patients with RV systolic dysfunction have worse clinical outcome regardless of the presence of RV dilation.

Evaluation and Management of Right-Sided Heart Failure: A Scientific Statement From the American Heart Association.

BACKGROUND AND PURPOSE: The diverse causes of right-sided heart failure (RHF) include, among others, primary cardiomyopathies with right ventricular (RV) involvement, RV ischemia and infarction, volume loading caused by cardiac lesions associated with congenital heart disease and valvular pathologies, and pressure loading resulting from pulmonic stenosis or pulmonary hypertension from a variety of causes, including left-sided heart disease. Progressive RV dysfunction in these disease states is associated with increased morbidity and mortality. The purpose of this scientific statement is to provide guidance on the assessment and management of RHF. METHODS: The writing group used systematic literature reviews, published translational and clinical studies, clinical practice guidelines, and expert opinion/statements to summarize existing evidence and to identify areas of inadequacy requiring future research. The panel reviewed the most relevant adult medical literature excluding routine laboratory tests using MEDLINE, EMBASE, and Web of Science through September 2017. The document is organized and classified according to the American Heart Association to provide specific suggestions, considerations, or reference to contemporary clinical practice recommendations. RESULTS: Chronic RHF is associated with decreased exercise tolerance, poor functional capacity, decreased cardiac output and progressive end-organ damage (caused by a combination of end-organ venous congestion and underperfusion), and cachexia resulting from poor absorption of nutrients, as well as a systemic proinflammatory state. It is the principal cause of death in patients with pulmonary arterial hypertension. Similarly, acute RHF is associated with hemodynamic instability and is the primary cause of death in patients presenting with massive pulmonary embolism, RV myocardial infarction, and postcardiotomy shock associated with cardiac surgery. Functional assessment of the right side of the heart can be hindered by its complex geometry. Multiple hemodynamic and biochemical markers are associated with worsening RHF and can serve to guide clinical assessment and therapeutic decision making. Pharmacological and mechanical interventions targeting isolated acute and chronic RHF have not been well investigated. Specific therapies promoting stabilization and recovery of RV function are lacking. CONCLUSIONS: RHF is a complex syndrome including diverse causes, pathways, and pathological processes. In this scientific statement, we review the causes and epidemiology of RV dysfunction and the pathophysiology of acute and chronic RHF and provide guidance for the management of the associated conditions leading to and caused by RHF.

High postoperative portal venous flow pulsatility indicates right ventricular dysfunction and predicts complications in cardiac surgery patients.

BACKGROUND: Right ventricular failure after cardiac surgery is associated with morbidity and mortality. Right ventricular dysfunction results in hepatic venous congestion, which impacts the portal circulation. We aimed to determine whether an increased portal flow pulsatility fraction was associated with right ventricular dysfunction in cardiac surgery patients. We also aimed to describe the haemodynamic factors and postoperative complications associated with an increased portal pulsatility in this setting. METHODS: We conducted a prospective single-centre cohort study, recruiting adults undergoing cardiac surgery. Portal flow was assessed before, during, and after surgery by Doppler ultrasound. A detailed haemodynamic and echocardiographic assessment was performed at the same time points. RESULTS: A total of 115 patients were included. Both systolic and diastolic right ventricular dysfunction were associated with a higher portal pulsatility fraction (P=0.008 and <0.001, respectively). A positive association was present between portal pulsatility fraction and measurements representative of venous pressure (central venous pressure, inferior vena cava diameter). A post-procedural portal pulsatility fraction ≥50% measured in the operating room was present in 21 (18.3%) patients and was associated with an increased risk of major complications (odds ratio=5.83, confidence interval, 2.04-16.68, P=0.001). The addition of portal flow assessment to a predictive model including EuroSCORE II and systolic right ventricular dysfunction improved prediction of postoperative complications. CONCLUSIONS: High portal flow pulsatility fraction is associated with right ventricular dysfunction, signs of venous congestion and decreased perfusion, and an increased risk of major complications. Portal vein Doppler ultrasound appears to be promising for risk assessment in the perioperative period. CLINICAL TRIALS REGISTRATION: NCT02658006.

Pulmonary Hypertension in Advanced Heart Failure: Assessment and Management of the Failing RV and LV.

PURPOSE OF REVIEW: In patients with heart failure with reduced ejection fraction, the presence of pulmonary hypertension (PH-LHD) has a significant impact on their prognosis. The purpose of this review is to explain the methods of diagnosing PH-LHD and then discuss the available therapeutic options. RECENT FINDINGS: We begin by examining the methods of assessment of PH-LHD-echocardiography, cardiopulmonary exercise testing, and right heart catheterization-with a particular focus on the importance of accurate measurement to ensure the proper determination of PH-LHD. We then focus primarily on management of PH-LHD, with an examination of trials of therapeutic options, use of mechanical circulatory support, and transplantation. This review highlights the complexities in diagnosis and management of PH-LHD. We outline a number of useful ways to maximize the yield of diagnostic testing, as well as give suggestions on the use of medical therapies, the role of both temporary mechanical support and left ventricular assist device, and finally the ways to best bridge these patients to transplantation.

Mechanical Circulatory Support Devices for Acute Right Ventricular Failure.

Right ventricular (RV) failure remains a major cause of global morbidity and mortality for patients with advanced heart failure, pulmonary hypertension, or acute myocardial infarction and after major cardiac surgery. Over the past 2 decades, percutaneously delivered acute mechanical circulatory support pumps specifically designed to support RV failure have been introduced into clinical practice. RV acute mechanical circulatory support now represents an important step in the management of RV failure and provides an opportunity to rapidly stabilize patients with cardiogenic shock involving the RV. As experience with RV devices grows, their role as mechanical therapies for RV failure will depend less on the technical ability to place the device and more on improved algorithms for identifying RV failure, patient monitoring, and weaning protocols for both isolated RV failure and biventricular failure. In this review, we discuss the pathophysiology of acute RV failure and both the mechanism of action and clinical data exploring the utility of existing RV acute mechanical circulatory support devices.

Right ventricular function in heart failure with preserved ejection fraction: a community-based study.

BACKGROUND: The prevalence and clinical significance of right ventricular (RV) systolic dysfunction (RVD) in patients with heart failure and preserved ejection fraction (HFpEF) are not well characterized. METHODS AND RESULTS: Consecutive, prospectively identified HFpEF (Framingham HF criteria, ejection fraction ≥50%) patients (n=562) from Olmsted County, Minnesota, underwent echocardiography at HF diagnosis and follow-up for cause-specific mortality and HF hospitalization. RV function was categorized by tertiles of tricuspid annular plane systolic excursion and by semiquantitative (normal, mild RVD, or moderate to severe RVD) 2-dimensional assessment. Whether RVD was defined by semiquantitative assessment or tricuspid annular plane systolic excursion ≤15 mm, HFpEF patients with RVD were more likely to have atrial fibrillation, pacemakers, and chronic diuretic therapy. At echocardiography, patients with RVD had slightly lower left ventricular ejection fraction, worse diastolic dysfunction, lower blood pressure and cardiac output, higher pulmonary artery systolic pressure, and more severe RV enlargement and tricuspid valve regurgitation. After adjustment for age, sex, pulmonary artery systolic pressure, and comorbidities, the presence of any RVD by semiquantitative assessment was associated with higher all-cause (hazard ratio=1.35; 95% confidence interval, 1.03-1.77; P=0.03) and cardiovascular (hazard ratio=1.85; 95% confidence interval, 1.20-2.80; P=0.006) mortality and higher first (hazard ratio=1.99; 95% confidence interval, 1.35-2.90; P=0.0006) and multiple (hazard ratio=1.81; 95% confidence interval, 1.18-2.78; P=0.007) HF hospitalization rates. RVD defined by tricuspid annular plane systolic excursion values showed similar but weaker associations with mortality and HF hospitalizations. CONCLUSIONS: In the community, RVD is common in HFpEF patients, is associated with clinical and echocardiographic evidence of more advanced HF, and is predictive of poorer outcomes.

Laterality of CT-measured hepatic extracellular volume fraction in patients with chronic thromboembolic pulmonary hypertension.

PURPOSE: This study examines the hepatic extracellular volume fraction (ECV) disparity between the left and right lobes (ECV_left and ECV_right) in patients with chronic thromboembolic pulmonary hypertension (CTEPH), its association with right heart catheterization (RHC) metrics, and with intolerance to increased pulmonary hypertension (PH)-targeted medication dosages. METHODS: We retrospectively analyzed 72 CTEPH-diagnosed patients who underwent equilibrium-phase abdominal dual-energy CT (DECT) and RHC. Hepatic ECVs, derived from DECT's iodine maps using circular regions of interest in the liver and aorta, were correlated with RHC parameters via Spearman's rank correlation and lobe differences through the Wilcoxon signed-rank test. Logistic regression assessed cases with ECV_left exceeding ECV_right by > 0.05, while receiver operating characteristic curve analysis gauged ECVs' predictive power for medication intolerance. RESULTS: Of the 72 patients (57 females; median age 69), ECV_total (0.24, IQR 0.20-0.27) moderately correlated with RHC parameters (rs = 0.28, -0.24, 0.3 for mean pulmonary arterial pressure, cardiac index [CI], and pulmonary vascular resistance index, respectively). ECV_left significantly surpassed ECV_right (0.25 vs. 0.22, p < 0.001), with a greater ECV_left by > 0.05 indicating notably lower CI (p < 0.001). In 27 patients on PH medication, ECV_left effectively predicted medication intolerance (AUC = 0.84). CONCLUSION: In CTEPH patients, hepatic ECV correlated with RHC metrics, where elevated left lobe ECV suggested reduced CI and potential medication intolerance.

Autonomic Dysregulation in Pulmonary Hypertension: Role of Physical Exercise.

Pulmonary hypertension (PH) is a rare and severe condition characterized by increased pressure in the pulmonary circulation, often resulting in right ventricular failure and death. The autonomic nervous system (ANS) plays a crucial role in the cardiovascular and pulmonary controls. Dysfunction of ANS has been implicated in the pathogenesis of cardiopulmonary diseases. Conversely, dysfunctions in ANS can arise from these diseases, impacting cardiac and pulmonary autonomic functions and contributing to disease progression. The complex interaction between ANS dysfunction and PH plays a crucial role in the disease progression, making it essential to explore interventions that modulate ANS, such as physical exercise, to improve the treatment and prognosis of patients with PH. This review addresses autonomic dysfunctions found in PH and their implications for the cardiopulmonary system. Furthermore, we discuss how physical exercise, a significant modulator of ANS, may contribute to the prognosis of PH. Drawing from evidence of aerobic and resistance exercise training in patients and experimental models of PH, potential cardiovascular benefits of exercise are presented. Finally, we highlight emerging therapeutic targets and perspectives to better cope with the complex condition. A comprehensive understanding of the interaction between ANS and PH, coupled with targeted physical exercise interventions, may pave the way for innovative therapeutic strategies and significantly improve the treatment and prognosis of vulnerable patients.

Tissue-Based Predictors of Impaired Right Ventricular Strain in Coronary Artery Disease: A Multicenter Stress Perfusion Study.

BACKGROUND: Right ventricular (RV) dysfunction is known to impact prognosis, but its determinants in coronary artery disease are poorly understood. Stress cardiac magnetic resonance (CMR) has been used to assess ischemia and infarction in relation to the left ventricle (LV); the impact of myocardial tissue properties on RV function is unknown. METHODS: Vasodilator stress CMR was performed in patients with known coronary artery disease at 7 sites between May 2005 and October 2018. Myocardial infarction was identified on late gadolinium enhancement-CMR, and infarct transmurality was graded on a per-segment basis. Ischemia was assessed on stress CMR based on first-pass perfusion and localized by using segment partitions corresponding to cine and late gadolinium enhancement analyses. RV function was evaluated by CMR-feature tracking for primary analysis with a global longitudinal strain threshold of 20% used to define impaired RV strain (RVIS); secondary functional analysis via RV ejection fraction was also performed. RESULTS: A total of 2604 patients were studied, among whom RVIS was present in 461 patients (18%). The presence and magnitude of RVIS were strongly associated with LV dysfunction, irrespective of whether measured by LV ejection fraction or wall motion score (P<0.001 for all). Regarding tissue substrate, regions of ischemic and dysfunctional myocardium (ie, hibernating myocardium) and infarct size were each independently associated with RVIS (both P<0.001). During follow-up (median, 4.62 [interquartile range, 2.15-7.67] years), 555 deaths (21%) occurred. Kaplan-Meier analysis for patients stratified by presence and magnitude of RV dysfunction by global longitudinal strain and RV ejection fraction each demonstrated strong prognostic utility for all-cause mortality (P<0.001). RVIS conferred increased mortality risk (hazard ratio, 1.35 [95% CI, 1.11-1.66]; P=0.003) even after controlling for LV function, infarction, and ischemia. CONCLUSIONS: RVIS in patients with known coronary artery disease is associated with potentially reversible LV processes, including LV functional impairment due to ischemic and predominantly viable myocardium, which confers increased mortality risk independent of LV function and tissue substrate.

Lethal complication: Ventricular septal perforation and right ventricular infarction after acute myocardial infarction.

Here, we report a case of ventricular septal perforation complicated with right ventricular infarction after inferior acute myocardial infarction, which was associated with a poor clinical outcome despite the successful surgical treatment.

Effects of BPA on right ventricular mechanical dysfunction in patients with inoperable CTEPH - A cardiac magnetic resonance study.

PURPOSE: The aim of this study was to assess effects of balloon pulmonary angioplasty (BPA) on right ventricular (RV) mechanical dysfunction in patients with inoperable chronic thromboembolic pulmonary hypertension (CTEPH) via MRI. METHOD: MRI at 1.5 Tesla and right heart catheterization were performed before and 6 months after BPA in 30 CTEPH patients (mean age 63.4 ± 10.6 years; 17 female). Feature-tracking strain analysis, including global longitudinal (GLS), circumferential (GCS), and radial (GRS) strain, was performed and compared with right ventricular function, myocardial remodelling (assessed by native T1 times), and pulmonary haemodynamics (mean pulmonary arterial pressure and pulmonary vascular resistance). RESULTS: RVEF (35.9% to 48.4%) increased and mPAP (42.1 mmHg to 33.1 mmHg) and PVR (551.8 to 377.7 dyn∙s/cm5) decreased after BPA (all p < 0.0001). Moreover, RV strain increased (GLS -19.9 to -24.0%, p = 0.0003; GCS -9.4 to -11.0%, p = 0.0022; GRS 38.2 to 50.7%, p = 0.001) and septal native area-adjusted T1 time (AA-T1) decreased (1019.4 to 988.7 ms, p < 0.0001). GLS revealed the best correlations with RVEF (before BPA r = -0.75; after BPA r = -0.54), mPAP (r = 0.36; r = 0.52), PVR (r = 0.49; r = 0.48), and AA-T1 (r = 0.44; 0.19). CONCLUSION: RV mechanical dysfunction, pulmonary haemodynamics, and myocardial remodelling are markedly improved by BPA. Moreover, RV strain values showed good correlations with RV function, pulmonary haemodynamics, and myocardial remodelling. Therefore, strain analysis might provide new insights regarding therapy outcome, monitoring, and prognosis.