Mechanisms Of Right Ventricular Dysfunction Research Articles

Strategies in Patients with Right Ventricular Failure on Mechanical Ventilation

Right ventricular failure is a complex clinical syndrome, and is a challenge for the intensivist to diagnose in critically ill patients, more so in patients receiving mechanical ventilation. Acute RV failure is a sudden deterioration of RV function and an inability of the RV to pump adequate cardiac output to the pulmonary circulation, thereby leading to inadequate cardiac output to the systemic circulation. The most common causes of acute RV failure are acute RV myocardial infarction, massive pulmonary embolism, congenital heart diseases, and severe pulmonary arterial hypertension. Over the years, RV has been considered a passive chamber of the heart and has received less focus about the way it functions and how efficiently the RV dysfunction can be managed. The National Heart Lung and Blood Institute in 2006 convened a working group to better understand the mechanisms of right ventricular dysfunction and the various ways and means to diagnose and manage right ventricular dysfunction.

Right ventricular area strain from 3-dimensional echocardiography: Mechanistic insight of right ventricular dysfunction in pediatric pulmonary hypertension

Right ventricular (RV) function is a major contributor to the outcome of pulmonary arterial hypertension (PAH). Adult studies demonstrated that regional and global changes in RV deformation are prognostic in PAH using 3-dimensional echocardiography (3DE). However, regional and global dynamic changes in RV mechanics have not been described in pediatric PAH. We compared 3DE RV regional and global deformation between pediatric patients who had associated PAH with congenital heart disease (APAH-CHD), pediatric patients who had idiopathic PAH (IPAH), and normal controls, and evaluated the clinical outcomes. A total of 48 controls, 47 patients with APAH-CHD, and 45 patients with IPAH were evaluated. 3DE RV sequences were analyzed and post-processed to extract global and regional deformation (circumferential, longitudinal, and area strain). Statistical analyses compared the sub-groups on the basis of global and regional deformation, and outcome analysis was performed. Patients with PAH had significantl8y different global and regional deformation (p < 0.001) compared with controls. Patients with APAH-CHD and and those with IPAH significantly differed in global circumferential strain (p < 0.010), area strain (inlet septum, p = 0.041), and circumferential strain at the inlet septum (p < 0.019), apex free wall (p < 0.004), and inlet free wall (p < 0.004). Circumferential strain at the inlet free wall and circumferential, longitudinal, and area strain at the apex free wall were predictors of adverse events. RV regional and global strain differ between controls and pediatric patients with PAH. RV apical free-wall area strain provides insight into the mechanism of RV dysfunction in pediatric patients with PAH, with regional strain emerging as outcome predictors, suggesting that this novel measure may be considered as a future measure of RV function.

Molecular mechanisms of right ventricular dysfunction in pulmonary arterial hypertension: focus on the coronary vasculature, sex hormones, and glucose/lipid metabolism.

Pulmonary arterial hypertension (PAH) is a rare, life-threatening condition characterized by dysregulated metabolism, pulmonary vascular remodeling, and loss of pulmonary vascular cross-sectional area due to a variety of etiologies. Right ventricular (RV) dysfunction in PAH is a critical mediator of both long-term morbidity and mortality. While combinatory oral pharmacotherapy and/or intravenous prostacyclin aimed at decreasing pulmonary vascular resistance (PVR) have improved clinical outcomes, there are currently no treatments that directly address RV failure in PAH. This is, in part, due to the incomplete understanding of the pathogenesis of RV dysfunction in PAH. The purpose of this review is to discuss the current understanding of key molecular mechanisms that cause, contribute and/or sustain RV dysfunction, with a special focus on pathways that either have led to or have the potential to lead to clinical therapeutic intervention. Specifically, this review discusses the mechanisms by which vessel loss and dysfunctional angiogenesis, sex hormones, and metabolic derangements in PAH directly contribute to RV dysfunction. Finally, this review discusses limitations and future areas of investigation that may lead to novel understanding and therapeutic interventions for RV dysfunction in PAH.

Postnatal Hyperoxia Exposure Durably Impairs Right Ventricular Function and Mitochondrial Biogenesis.

Prematurity complicates 12% of births, and young adults with a history of prematurity are at risk to develop right ventricular (RV) hypertrophy and impairment. The long-term risk for pulmonary vascular disease, as well as mechanisms of RV dysfunction and ventricular-vascular uncoupling after prematurity, remain poorly defined. Using an established model of prematurity-related lung disease, pups from timed-pregnant Sprague Dawley rats were randomized to normoxia or hyperoxia (fraction of inspired oxygen, 0.85) exposure for the first 14 days of life. After aging to 1 year in standard conditions, rats underwent hemodynamic assessment followed by tissue harvest for biochemical and histological evaluation. Aged hyperoxia-exposed rats developed significantly greater RV hypertrophy, associated with a 40% increase in RV systolic pressures. Although cardiac index was similar, hyperoxia-exposed rats demonstrated a reduced RV ejection fraction and significant RV-pulmonary vascular uncoupling. Hyperoxia-exposed RV cardiomyocytes demonstrated evidence of mitochondrial dysregulation and mitochondrial DNA damage, suggesting potential mitochondrial dysfunction as a cause of RV dysfunction. Aged rats exposed to postnatal hyperoxia recapitulate many features of young adults born prematurely, including increased RV hypertrophy and decreased RV ejection fraction. Our data suggest that postnatal hyperoxia exposure results in mitochondrial dysregulation that persists into adulthood with eventual RV dysfunction. Further evaluation of long-term mitochondrial function is warranted in both animal models of premature lung disease and in human adults who were born preterm.

Hemodynamic Predictors of Survival in Scleroderma-related Pulmonary Arterial Hypertension

Pulmonary arterial hypertension (PAH) related to systemic sclerosis (SSc) has a poorer prognosis compared with other forms of PAH for reasons that remain unexplained. To identify risk factors of mortality in a well-characterized cohort of patients with PAH related to systemic sclerosis (SSc-PAH). Seventy-six consecutive patients with SSc (64 women and 12 men; mean age 61 +/- 11 yr) were diagnosed with PAH by heart catheterization in a single center, starting in January 2000, and followed over time. Kaplan-Meier estimates were calculated and mortality risk factors were analyzed. Forty (53%) patients were in World Health Organization functional class III or IV. Mean pulmonary artery pressure was 41 +/- 11 mm Hg, pulmonary vascular resistance (PVR) was 8.6 +/- 5.6 Wood units, and cardiac index was 2.4 +/- 0.7 L/min/m(2). Median follow-up time was 36 months, with 42 deaths observed. Survival estimates were 85%, 72%, 67%, 50%, and 36% at 1, 2, 3, 4, and 5 years, respectively. Multivariate analysis identified PVR (hazard ratio [HR], 1.10; 95% confidence interval [CI], 1.03-1.18; P < 0.01), stroke volume index (HR, 0.94; 95% CI, 0.89-0.99; P = 0.02), and pulmonary arterial capacitance (HR, 0.43; 95% CI, 0.20-0.91; P = 0.03) as strong predictors of survival. An estimated glomerular filtration rate less than 60 ml/min/1.73 m(2) portended a threefold risk of mortality. Our results suggest that specific components of right ventricular dysfunction and renal impairment contribute to increased mortality in SSc-PAH. Understanding the mechanisms of right ventricular dysfunction in response to increased afterload should lead to improved targeted therapy in these patients.

227 Strain rate imaging reveals myocardial ischemia as mechanism of right ventricular dysfunction after acute pulmonary embolism

evaluation before treadmill EE using the modified Bruce protocol. Pulmonary artery systolic pressure (PASP) was estimated in left lateral desubitus, in upright position before exercise was started and at peak workload from peak tricuspid regurgitant jet velocities according to the equation: PASP=4V2+5mmHg. PASP 60mmHg Conclusions: A high percentage (62%) of CMD pts with normal PASP at rest revealed a pathological increase of PASP during treadmill exercise, classified as severe in 3 of them. The clinical significance of these findings are not known but might reveal the usefulness of EE in the early screening of PAH and underscore the need for long term follow-up of these pts with the purpose of clarifying the clinical implications of our study.

Acute pulmonary embolism: part I: epidemiology, pathophysiology, and diagnosis.

This New Frontiers article reviews the epidemiology, pathophysiology, diagnosis, treatment, and prevention of pulmonary embolism (PE) in 2 parts. In this first section we summarize the mechanisms of right ventricular dysfunction, arterial hypoxemia, and other abnormalities of gas exchange. For diagnosis, we streamline and expedite the work-up. For the second part we provide a contemporary approach to risk stratification to determine which patients may warrant intervention beyond use of heparin and warfarin alone. We conclude with an overview of contemporary concepts in optimizing prophylaxis. PE is a common cardiovascular and cardiopulmonary illness with an incidence in the United States that exceeds 1 per 1000 and a mortality rate 15% in the first 3 months after diagnosis. 1 This makes PE possibly as deadly an illness as acute myocardial infarction. Nevertheless, the lay public has not been well educated about PE. Consequently, early detection and prompt presentation for medical evaluation have lagged far behind the public awareness of acute coronary syndromes and stroke. Although discussion of the etiology of PE has classically focused on acquired and inherited causes of hypercoagulability, there is also an association between atherosclerotic disease and spontaneous venous thrombosis.2 The most common reversible risk factor for PE is obesity, an increasing pandemic in our society. Other common reversible risk factors include cigarette smoking and hypertension. Nevertheless, public fascination with PE has centered on long-haul air travel, a rare cause of venous thromboembolism. 3 PE also occurs in the context of illness attributable to surgery, trauma, immobilization, cancer,4 oral contraceptives,5 pregnancy, and postmenopausal hormone replacement therapy, 6 as well as medical conditions such as pneumonia and congestive heart failure. Genetic predisposition to venous thrombosis is being increasingly recognized, 7 and twin studies have demonstrated the important contribution of an inherited prothrombotic state. 8 Increased levels of clotting factors and activation peptides contribute to the risk of PE. Deficiencies of anticoagulant factors also increase thrombotic risk.9 Pathophysiology

Mechanisms of right ventricular dysfunction after pulmonary resection

Significant right ventricular (RV) dysfunction as measured by increased end-diastolic volume and reduced ejection fraction has been documented in the postoperative period after pulmonary resection. We hypothesized that changes in RV contractile state or afterload may contribute to this RV pump dysfunction. In part one of the study, RV preload was altered on postoperative day 2 (n = 6) by rapid infusion of Hespan to a total of 250, 500, and 1,000 mL. The relationship between RV stroke work and end-diastolic volume was plotted using linear regression. This preload recruitable stroke work relation had been previously validated as a load-insensitive index of RV contractility. The slopes of the preoperative relation (n = 35) and postoperative relation were compared. In part two of the study, RV afterload was reduced by continuous infusion of prostaglandin E1 (n = 6) through postoperative day 2 and RV pump function was assessed. Comparison of the slopes of the preload recruitable stroke work relation plotted preoperatively and on postoperative day 2 revealed no significant difference, indicating no change in RV contractile state. Infusion of prostaglandin E1 in the postoperative period (n = 6) significantly reduced pulmonary vascular resistance (3.67 +/- 0.19 versus baseline 5.72 +/- 0.19 dyne . s . cm-5/ m2; p < 0.05). However, RV ejection fraction remained significantly reduced (0.34 +/- 0.01 versus baseline 0.42 +/- 0.01; p < 0.05) and end-diastolic volume significantly increased (105 +/- 5 versus baseline 93 +/- 2 mL/m2; p < 0.05). Heart rate was increased compared with baseline throughout the postoperative period. The present study suggests that RV dysfunction after pulmonary resection is not caused by primary alterations in contractility or immediate changes in afterload. Better control of heart rate with minimal effect on inotropy may enhance RV pump function.