Survival in patients with pulmonary arterial hypertension (PAH) is closely related to right ventricular (RV) function. Although pulmonary load is an important determinant of RV systolic function in PAH, there remains a significant variability in RV adaptation to pulmonary hypertension. In this report, the authors discuss the emerging concepts of right heart pathobiology in PAH. More specifically, the discussion focuses on the following questions. 1) How is right heart failure syndrome best defined? 2) What are the underlying molecular mechanisms of the failing right ventricle in PAH? 3) How are RV contractility and function and their prognostic implications best assessed? 4) What is the role of targeted RV therapy? Throughout the report, the authors highlight differences between right and left heart failure and outline key areas of future investigation.

TAPSE powerfully reflects RV function and prognosis in PAH.

Rationale: Transthoracic Doppler echocardiography is recommended for screening for the presence of pulmonary hypertension (PH). However, some recent studies have suggested that Doppler echocardiographic pulmonary artery pressure estimates may frequently be inaccurate. Objectives: Evaluate the accuracy of Doppler echocardiography for estimating pulmonary artery pressure and cardiac output. Methods: We conducted a prospective study on patients with various forms of PH who underwent comprehensive Doppler echocardiography within 1 hour of a clinically indicated right-heart catheterization to compare noninvasive hemodynamic estimates with invasively measured values. Measurements and Main Results: A total of 65 patients completed the study protocol. Using Bland-Altman analytic methods, the bias for the echocardiographic estimates of the pulmonary artery systolic pressure was 20.6 mm Hg with 95% limits of agreement ranging from 138.8 to 240.0 mm Hg. Doppler echocardiography was inaccurate (defined as being greater than 610 mm Hg of the invasive measurement) in 48% of cases. Overestimation and underestimation of pulmonary artery systolic pressure by Doppler echocardiography occurred with a similar frequency (16 vs. 15 instances, respectively). The magnitude of pressure underestimation was greater than overestimation (230 6 16 vs. 119 6 11 mm Hg; P 5 0.03); underestimates by Doppler also led more often to misclassification of the severity of the PH. For cardiac output measurement, the bias was 20.1 L/min with 95% limits of agreement ranging from 12.2 to 22.4 L/min. Conclusions: Doppler echocardiography may frequently be inaccurate in estimating pulmonary artery pressure and cardiac output in patients being evaluated for PH.Keywords: echocardiography; pulmonary hypertension; pulmonary systolic pressure; cardiac output; accuracy Pulmonary hypertension (PH), a syndrome characterized by increased pulmonary vascular resistance and remodeling, is associated with significant morbidity and mortality, which are directly related to cardiac function (1). Although the definitive diagnosis of PH is currently established through right-heart catheterization, accurate noninvasive assessment of pulmonary arterial pressure and cardiac output (CO) is desirable both for diagnostic purposes and to assess response to therapy.Transthoracic Doppler echocardiography (DE) is recommended as the initial noninvasive modality in the screening and evaluation of PH (2). Echocardiography can be used to evaluate right-sided chamber size and function and the presence of pericardial effusion, which are known to impact survival (3-5). Frequently, DE is used to estimate the right ventricular systolic pressure by estimating the pressure gradient between the right ventricle and the right atrium using the modified Bernoulli equation, 4v 2 , where v equals the velocity of the tricuspid regurgitant jet. An estimated right atrial pressure is added to this number to approximate the right ventricular systolic pressure, which equals the pulmonary artery systolic pres...

Background: The prevalence and clinical significance of right ventricular (RV) systolic dysfunction (RVD) in patients with heart failure and preserved EF (HFpEF) are not well characterized. Methods and Results: Consecutive, prospectively identified HFpEF (Framingham HF criteria, EF ≥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 (TAPSE) and by semi-quantitative (normal, mild RVD or moderate-severe RVD) 2D assessment. Whether RVD was defined by semi-quantitative assessment or TAPSE ≤ 15 mm, HFpEF patients with RVD were more likely to have atrial fibrillation, pacemakers and chronic diuretic therapy. At echo, patients with RVD had slightly lower LVEF, worse diastolic dysfunction, lower blood pressure and cardiac output, higher pulmonary artery systolic pressure (PASP), and more severe RV enlargement and tricuspid valve regurgitation. Adjusting for age, sex, PASP and comorbidities, the presence of any RVD by semi-quantitative assessment was associated with higher all-cause (hazard ratio (HR) = 1.35 (1.03-1.77; p=0.03)) and cardiovascular (HR=1.85 (1.20-2.80; p=0.006)) mortality and higher first (HR=1.99 (1.35-2.90; p=0.0006) and multiple (HR=1.81 (1.18-2.78; p=0.007) HF hospitalization rates. RVD defined by TAPSE values showed similar but weaker associations with mortality and HF hospitalizations. Conclusions: In the community, RVD is common in HFpEF patients, associated with clinical and echocardiographic evidence of more advanced HF and predictive of poorer outcomes.

Visual inspection of the shape of the FVE(RVOT) provides insight into the hemodynamic basis of PH in a referral PH cohort. MSN is associated with the most severe pulmonary vascular disease and right heart dysfunction.

This study determined the changes in NO production from the coronary circulation of the conscious dog during exercise. The role of endogenous NO as it relates to coronary flow, myocardial work, and metabolism was also studied. Mongrel dogs were chronically instrumented for measurements of coronary blood flow (CBF), ventricular and aortic pressure, and ventricular diameter, with catheters in the aorta and coronary sinus. Acute exercise (5 minutes at 3.6, 5.9, and 9.1 mph) was performed, and hemodynamic measurements and blood samples were taken at each exercise level. Nitro-L-arginine (NLA, 35 mg/kg IV) was given to block NO synthesis, and the exercise was repeated. Blood samples were analyzed for oxygen, plasma nitrate/nitrite (an index of NO), lactate, glucose, and free fatty acid (FFA) levels. Acute exercise caused significant elevations in NO production by the coronary circulation (46 +/- 23, 129 +/- 44, and 63 +/- 32 nmol/min at each speed respectively, P < .05). After NLA, there was no measurable NO production at rest or during exercise. Blockade of NO synthesis resulted in elevations in myocardial oxygen consumption and reductions in myocardial FFA consumption for comparable levels of CBF and cardiac work. The metabolic changes after NLA occurred in the absence of alterations in myocardial lactate or glucose consumptions. NO production by the coronary circulation is increased with exercise and blocked by NLA. The absence of NO in the coronary circulation during exercise does not affect levels of CBF, because it shifts the relationship between cardiac work and myocardial oxygen consumption, suggesting that endogenous NO modulates myocardial metabolism.

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These studies indicate that nitrate is a reliable measure of NO metabolism in vivo but that because of the long half-life, nitrate will accumulate in plasma once it is produced. Because of the large volume of distribution (21% of body weight versus the 4% of body weight usually attributed to plasma volume, the compartment in which nitrate is measured), simple measures of plasma nitrate underestimate by a factor of 4 to 6 the actual production of nitrate or NO by the body. In disease states, such as heart failure, in which renal function and extracellular volume are altered, caution should be exercised when increases in nitrate in plasma as an index of NO formation are evaluated.