Multimodality Evaluation of Aortic Insufficiency and Aortitis in Rheumatologic Diseases.

Aortic insufficiency is commonly observed in rheumatologic diseases such as ankylosing spondylitis, systemic lupus erythematosus, antiphospholipid syndrome, Behçet's disease, granulomatosis with polyangiitis, and Takayasu arteritis. Aortic insufficiency with an underlying rheumatologic disease may be caused by a primary valve pathology (leaflet destruction, prolapse or restriction), annular dilatation due to associated aortitis or a combination of both. Early recognition of characteristic valve and aorta morphology on cardiac imaging has both diagnostic and prognostic importance. Currently, echocardiography remains the primary diagnostic tool for aortic insufficiency. Complementary use of computed tomography, cardiac magnetic resonance imaging and positron emission tomography in these systemic conditions may augment the assessment of underlying mechanism, disease severity and identification of relevant non-valvular/extracardiac pathology. We aim to review common rheumatologic diseases associated with aortic insufficiency and describe their imaging findings that have been reported in the literature.

Imaging Assessment of Endothelial Function: An Index of Cardiovascular Health.

Endothelial dysfunction is a key early mechanism in a variety of cardiovascular diseases and can be observed in larger conduit arteries as well as smaller resistance vessels (microvascular dysfunction). The presence of endothelial dysfunction is a strong prognosticator for cardiovascular events and mortality, and assessment of endothelial function can aid in selecting therapies and testing their response. While the gold standard method of measuring coronary endothelial function remains invasive angiography, several non-invasive imaging techniques have emerged for investigating both coronary and peripheral endothelial function. In this review, we will explore and summarize the current invasive and non-invasive modalities available for endothelial function assessment for clinical and research use, and discuss the strengths, limitations and future applications of each technique.

Cardiovascular Imaging in Stress Cardiomyopathy (Takotsubo Syndrome).

Stress cardiomyopathy (Takotsubo syndrome) is a reversible syndrome stemming from myocardial injury leading to systolic dysfunction and is usually noted in the setting of a stressful event, be it an emotional or physical trigger. While the exact pathophysiology behind stress cardiomyopathy is yet unknown, there is ample evidence suggesting that neurocardiogenic mechanisms may play an important role. Although historically stress cardiomyopathy was generally thought to be a relatively benign condition, there is growing recognition of the cardiovascular complications associated with it despite its reversibility. Our review aims to shed light onto key cardiovascular imaging modalities used to diagnose stress cardiomyopathy while highlighting the role that imaging plays in assessing disease severity, identifying complications, dictating treatment approaches, and in short-term and long-term prognosis.

Defining the Role of Point-of-Care Ultrasound in Cardiovascular Disease.

Echocardiography is the foundation for diagnostic cardiac testing, allowing for direct identification and management of various conditions. Point-of-care ultrasound (POCUS) has emerged as an invaluable tool for bedside diagnosis and management. The objective of this review is to address the current use and clinical applicability of POCUS to identify, triage, and manage a wide spectrum of cardiac conditions. POCUS can change diagnosis and management decisions of various cardiovascular conditions in a range of settings. In the outpatient setting, it is used to risk stratify and diagnose a variety of medical conditions. In the emergency department (ED) and critical care settings, it is used to guide triage and critical care interventions. Furthermore, the skills needed to perform POCUS can be taught to noncardiologists in a way that is retained and allows identification of normal and grossly abnormal cardiac findings. Various curricula have been developed that teach residents and advanced learners how to appropriately employ point-of-care ultrasound. In conclusion, POCUS can be a useful adjunct to the physical exam, particularly in critical care applications.

A novel bedside cardiopulmonary physical diagnosis curriculum for internal medicine postgraduate training.

BACKGROUND: Physicians spend less time at the bedside in the modern hospital setting which has contributed to a decline in physical diagnosis, and in particular, cardiopulmonary examination skills. This trend may be a source of diagnostic error and threatens to erode the patient-physician relationship. We created a new bedside cardiopulmonary physical diagnosis curriculum and assessed its effects on post-graduate year-1 (PGY-1; interns) attitudes, confidence and skill. METHODS: One hundred five internal medicine interns in a large U.S. internal medicine residency program participated in the Advancing Bedside Cardiopulmonary Examination Skills (ACE) curriculum while rotating on a general medicine inpatient service between 2015 and 2017. Teaching sessions included exam demonstrations using healthy volunteers and real patients, imaging didactics, computer learning/high-fidelity simulation, and bedside teaching with experienced clinicians. Primary outcomes were attitudes, confidence and skill in the cardiopulmonary physical exam as determined by a self-assessment survey, and a validated online cardiovascular examination (CE). RESULTS: Interns who participated in ACE (ACE interns) by mid-year more strongly agreed they had received adequate training in the cardiopulmonary exam compared with non-ACE interns. ACE interns were more confident than non-ACE interns in performing a cardiac exam, assessing the jugular venous pressure, distinguishing 'a' from 'v' waves, and classifying systolic murmurs as crescendo-decrescendo or holosystolic. Only ACE interns had a significant improvement in score on the mid-year CE. CONCLUSIONS: A comprehensive bedside cardiopulmonary physical diagnosis curriculum improved trainee attitudes, confidence and skill in the cardiopulmonary examination. These results provide an opportunity to re-examine the way physical examination is taught and assessed in residency training programs.

Cardiac Safety of TGF-ß Receptor I Kinase Inhibitor LY2157299 Monohydrate in Cancer Patients in a First-in-Human Dose Study.

Transforming growth factor-beta (TGF-ß) signaling plays an important role in the fetal development of cardiovascular organs and in the repair mechanisms of the heart. Hence, inhibitors of the TGF-ß signaling pathway require a careful identification of a safe therapeutic window and a comprehensive monitoring of the cardiovascular system. Seventy-nine cancer patients (67 glioma and 12 solid tumor) enrolled in a first-in-human dose study and received the TGF-ß inhibitor LY2157299 monohydrate (LY2157299) as monotherapy (n = 53) or in combination with lomustine (n = 26). All patients were monitored using 2D echocardiography/color and Spectral Doppler (2D Echo with Doppler) every 2 months, monthly electrocardiograms, thorax computer tomography scans every 6 months, and monthly serum brain natriuretic peptide (BNP), troponin I, cystatin C, high-sensitivity C-reactive protein (hs-CRP). Administration of LY2157299 was not associated with medically relevant cardiovascular toxicities, including patients treated ≥6 months (n = 13). There were no increases of troponin I, BNP, or hs-CRP or reduction in cystatin C levels, which may have been considered as signs of cardiovascular injury. Blood pressure was generally stable during treatment. Imaging with echocardiography/Doppler showed an increase in mitral and tricuspid valve regurgitation by two grades of severity in only one patient with no concurrent clinical symptoms of cardiovascular injury. Overall, this comprehensive cardiovascular monitoring for the TGF-ß inhibitor LY2157299 did not detect medically relevant cardiac toxicity and hence supports the evaluation of LY2157299 in future clinical trials.

Omega-3 in SLE: a double-blind, placebo-controlled randomized clinical trial of endothelial dysfunction and disease activity in systemic lupus erythematosus.

Accelerated atherosclerosis remains a major cause of death in late systemic lupus erythematosus (SLE). Omega-3 has been reported to have benefit for endothelial dysfunction, one of the earliest stages of atherosclerosis, and to reduce disease activity in SLE. We performed a randomized, double-blind placebo-controlled trial to examine the effect of Omega-3 on endothelial function, disease activity, inflammatory markers and lipids in SLE. SLE patients (n = 85, mean age 47, 55% Caucasian, 38% African-American, 94% female) were randomly assigned to 3 g of Omega-3 (Lovaza, GSK) versus placebo for 12 weeks. Endothelial function was measured at baseline and at 12 weeks using flow-mediated dilation, calculated using high-resolution B-mode ultrasound of the brachial artery diameter in response to vasoactive stimuli (hyperemia). Disease activity was measured using the physician global assessment and SELENA-SLEDAI score. Inflammatory markers (sICAM-1, sVCAM-1, IL-6) and fasting lipid profile were done at baseline and 12-week follow-up. There was no difference between the treatment groups with respect to changes in flow-mediated dilation parameters or disease activity. An average increase in LDL cholesterol of 3.11 mg/dL (±21.99) was found with Omega-3 versus a decrease of 1.87 mg/dL (±18.29) with placebo (p = 0.0266). In this trial, Omega-3 did not improve endothelial function, disease activity, nor reduce inflammatory markers in SLE. Longer trials might be required if there are delayed clinical effects. There was evidence that Omega-3 may increase LDL cholesterol, but not the LDL/HDL ratio.

Tetralogy of Fallot and aortic root dilation: a long-term outlook.

Dilation of the sinus of Valsalva (SoV) has been increasingly observed after repaired tetralogy of Fallot (TOF). We estimate the prevalence of SoV dilation in adults with repaired TOF and analyze possible factors related to aortic disease. Adults with TOF [n = 109, median age 33.2 years (range 18.1 to 69.5)] evaluated at Johns Hopkins Hospital from 2001 to 2009 were reviewed in an observational retrospective cohort study. Median follow-up was 27.3 (range 0.1-48.8) years. SoV dilation was defined as >95 % confidence interval adjusted for age and body surface area (z-score > 2). The prevalence of SoV dilation was 51 % compared with that of a normal population with a mean z-score of 2.03. Maximal aortic diameters were ≥ 4 cm in 39 % (42 of 109), ≥ 4.5 cm in 21 % (23 of 109), ≥ 5 cm in 8 % (9 of 109), and ≥ 5.5 cm in 2 % (2 of 109). There was no aortic dissection or death due contributable to aortic disease. Aortic valve replacement was performed in 1.8 % and aortic root or ascending aorta (AA) replacement surgery in 2.8 % of patients. By multivariate logistic regression analysis, aortic regurgitation (AR) [odds ratio (OR) = 3.09, p = 0.005], residual ventricular septal defect (VSD) (OR = 4.14, p < 0.02), and TOF with pulmonary atresia (TOF/PA) (OR = 6.75, p = 0.03) were associated with increased odds of dilated aortic root. SoV dilation after TOF repair is common and persists with aging. AR, residual VSD, and TOF/PA are associated with increased odds of dilation. AA evaluation beyond the SoV is important. Indexed values are imperative to avoid bias on the basis of age and body surface area.

Influence of atrial function and mechanical synchrony on LV hemodynamic status in heart failure patients on resynchronization therapy.

OBJECTIVES: The aim of this study was to evaluate atrial and ventricular function in patients undergoing cardiac resynchronization therapy (CRT). BACKGROUND: Right atrial pacing (AP) in CRT induces delays in electrical and mechanical activation of the left atrium. The influence of atrial sensing (AS) versus AP on ventricular performance in CRT and the mechanisms underlying the differences between AS and AP in CRT have not been fully elucidated. METHODS: Fifty-five patients with heart failure undergoing CRT for 9 ± 12.5 months and 22 control subjects without heart failure were enrolled. Conventional and tissue Doppler echocardiography was performed to examine atrial and ventricular mechanics and hemodynamic status. RESULTS: The optimal atrioventricular interval was shorter in AS compared with AP mode (126 ± 19 ms vs. 155 ± 20 ms, p < 0.0001). Left ventricular (LV) outflow tract time-velocity integral (22 ± 7 cm vs. 20 ± 7 cm, p < 0.001), diastolic filling period (468 ± 124 ms vs. 380 ± 93 ms, p < 0.001), and global strain (-32 ± 24% vs. -27 ± 22%, p = 0.001) were greater in AS compared with AP mode. Atrial strain was higher in AS compared with AP mode in the right atrium (-28.2 ± 8.6% vs. -22.6 ± 7.6%, p = 0.0007), interatrial septum (-17.1 ± 6.5% vs. -13.2 ± 5.4%, p = 0.002), and left atrium (-16.4 ± 11.0% vs. -13.6 ± 8.5%, p = 0.02). There was no difference in intraventricular dyssynchrony but significantly lower atrial dyssynchrony in AS compared with AP mode (31 ± 19 ms vs. 42 ± 24 ms, p = 0.0002). CONCLUSIONS: AS is associated with preserved atrial contractility and atrial synchrony, resulting in optimal LV diastolic filling, stroke volume, and LV systolic mechanics. This pacing mode maximizes LV performance and the hemodynamic benefit of CRT in patients with heart failure.

Hypertrophy-associated polymorphisms ascertained in a founder cohort applied to heart failure risk and mortality.

A three-stage approach was undertaken using genome-wide, case-control, and case-only association studies to identify genetic variants associated with heart failure mortality. In an Amish founder population (n = 851), cardiac hypertrophy, a trait integral to the adaptive response to failure, was found to be heritable (h² = 0.28, p = 0.0002) and GWAS revealed 21 candidate hypertrophy SNPs. In a case (n = 1,610)-control (n = 463) study in unrelated Caucasians, one of the SNPs associated with hypertrophy (rs2207418, p = 8 × 10⁻6), was associated with heart failure, RR = 1.85(1.25-2.73, p = 0.0019). In heart failure cases rs2207418 was associated with increased mortality, HR = 1.51(1.20-1.97, p = 0.0004). There was consistency between studies, with the GG allele being associated with increased ventricular mass (~13 g/m²) in the Amish, heart failure risk, and heart failure mortality. This SNP is in a gene desert of chromosome 20p12. Five genes are within 2.0 mbp of rs2207418 but with low LD between their SNPs and rs2207418. A region near this SNP is highly conserved in multiple vertebrates (lod score = 1,208). This conservation and the internal consistency across studies suggests that this region has biologic importance in heart failure, potentially acting as an enhancer or repressor element. rs2207418 may be useful for predicting a more progressive form of heart failure that may require aggressive therapy.

Accuracy of Doppler echocardiography in the hemodynamic assessment of pulmonary hypertension.

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 -0.6 mm Hg with 95% limits of agreement ranging from +38.8 to -40.0 mm Hg. Doppler echocardiography was inaccurate (defined as being greater than +/-10 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 (-30 +/- 16 vs. +19 +/- 11 mm Hg; P = 0.03); underestimates by Doppler also led more often to misclassification of the severity of the PH. For cardiac output measurement, the bias was -0.1 L/min with 95% limits of agreement ranging from +2.2 to -2.4 L/min. CONCLUSIONS: Doppler echocardiography may frequently be inaccurate in estimating pulmonary artery pressure and cardiac output in patients being evaluated for PH.

The genetic response to short-term interventions affecting cardiovascular function: rationale and design of the Heredity and Phenotype Intervention (HAPI) Heart Study.

BACKGROUND: The etiology of cardiovascular disease (CVD) is multifactorial. Efforts to identify genes influencing CVD risk have met with limited success to date, likely because of the small effect sizes of common CVD risk alleles and the presence of gene by gene and gene by environment interactions. METHODS: The HAPI Heart Study was initiated in 2002 to measure the cardiovascular response to 4 short-term interventions affecting cardiovascular risk factors and to identify the genetic and environmental determinants of these responses. The measurements included blood pressure responses to the cold pressor stress test and to a high salt diet, triglyceride excursion in response to a high-fat challenge, and response in platelet aggregation to aspirin therapy. RESULTS: The interventions were carried out in 868 relatively healthy Amish adults from large families. The heritabilities of selected response traits for each intervention ranged from 8% to 38%, suggesting that some of the variation associated with response to each intervention can be attributed to the additive effects of genes. CONCLUSIONS: Identifying these response genes may identify new mechanisms influencing CVD and may lead to individualized preventive strategies and improved early detection of high-risk individuals.

Diagnostic accuracy of arterial phase 64-slice multidetector CT angiography for left atrial appendage thrombus in patients undergoing atrial fibrillation ablation.

INTRODUCTION: Multidetector CT (MDCT) is used prior to atrial fibrillation ablation (AFA) to anatomically guide ablation procedures. Whether 64-slice MDCT also can be used to diagnose left atrial thrombus is not known. METHODS: We sought to determine the accuracy and interobserver variability of MDCT in the evaluation of left atrial thrombus prior to AFA. We enrolled 50 patients scheduled for AFA who underwent 64-slice MDCT scan and transesophageal echocardiography prior to the procedure. Three experienced observers reviewed all the MDCT images for the presence of a left atrial thrombus, and two different readers interpreted the transesophageal echocardiograms (TEE), which were used as the gold standard. All observers were blinded to clinical data and each other. RESULTS: Interobserver variability between the three MDCT readers was poor (highest kappa statistic 0.43, P = 0.001). Diagnostic accuracy was highly variable, with sensitivities ranging from 100% to 50% and specificities ranging from 85% to 44%. TEE reader agreement was 98%. CONCLUSION: MDCT demonstrates high interobserver variability and has only modest diagnostic accuracy for the detection of left atrial thrombus in patients undergoing AFA procedure. Potential factors affecting the accuracy of MDCT include image quality and the difficulty of distinguishing clot from pectinate muscle. MDCT likely is not the optimal method to detect left atrial thrombus using current techniques and standards of interpretation.

Utility of tissue Doppler and strain echocardiography in arrhythmogenic right ventricular dysplasia/cardiomyopathy.

Arrhythmogenic right ventricular dysplasia (ARVD) is a heritable cardiomyopathy characterized by the fibrofatty replacement of right ventricular (RV) myocardium leading to RV failure and arrhythmias. This study evaluated the potential utility of tissue Doppler echocardiography (TDE) and strain echocardiography (SE) to quantitatively assess RV function and their potential role in diagnosing ARVD. Images of 30 patients with ARVD (diagnosed by task force criteria) and 36 healthy controls were obtained. Peak systolic velocity, early diastolic velocity, displacement, strain rate, strain, outflow tract diameter, and fractional RV area change were measured in all subjects. Peak RV systolic velocity (6.4 +/- 2.2 vs 9 +/- 1.6 cm/s, p <0.0001), early diastolic velocity (-6.7 +/- 2.7 vs -9.4 +/- 2 cm/s, p <0.0001), displacement (13.7 +/- 5.8 vs 18.7 +/- 3.5 mm, p <0.0003), strain rate (-1 +/- 0.7 vs -2 +/- 1 s(-1), p = 0.002), and strain (-10 +/- 6% vs -28 +/- 11%, p = 0.001) were significantly lower in patients with ARVD compared with controls, respectively. Sensitivity and specificity, respectively, were 67% and 89% for systolic velocity, 77% and 71% for displacement, 73% and 87% for strain, 50% and 96% for strain rate, 53% and 93% for outflow tract diameter, and 47% and 83% for fractional area change. RV systolic velocity and displacement were significantly lower than in controls, even in the subset of patients with ARVD with apparently normal right ventricles by conventional echocardiography. Inter- and intraobserver agreement was high. In conclusion, TDE and SE enable the detection of ARVD via the quantification of RV function and may have potential clinical value in the assessment of patients with suspected ARVD. Peak RV systolic velocity <7.5 cm/s and peak RV strain <18% best identify patients with ARVD.

Comparison of novel echocardiographic parameters of right ventricular function with ejection fraction by cardiac magnetic resonance.

BACKGROUND: Assessment of right ventricular (RV) function by echocardiography is challenging. Newer techniques such as tissue Doppler echocardiography and strain echocardiography may allow accurate and quantitative assessment of RV function. We sought to determine which echocardiographic variable or variables best correlated with RV ejection fraction (RVEF) by cardiac magnetic resonance. METHODS: We performed conventional echocardiography, tissue Doppler echocardiography, strain echocardiography, and cardiac magnetic resonance on 53 individuals, of which 10 patients had arrhythmogenic RV dysplasia without pulmonary hypertension, and 43 were control subjects. RV fractional area change (FAC), Tei index, isovolumic acceleration, peak systolic velocity (S'), tissue displacement, systolic strain (Ss) rate, and Ss were measured. RESULTS: RVEF, FAC, S', tissue displacement, isovolumic acceleration, Ss rate, and Ss were significantly lower in patients compared with control subjects (P < or = .05 in all) but not the Tei index (P = .07). Regression analysis revealed a significant correlation between S', tissue displacement, Ss rate, Ss, and FAC with RVEF (P < .05 for all) but not with isovolumic acceleration and Tei index (P = .13 and .39, respectively). Multivariate analysis demonstrated a persistent significant relationship between S' and FAC with RVEF (both P < .05). However, feasibility, and intraobserver and interobserver agreement, were substantially lower for FAC. A cut-off value of 8.8 cm/s for S' had sensitivity and specificity of 80% and 79% (area under the curve 0.87, P = .01), respectively, for prediction of RVEF less than 45%. CONCLUSION: Tissue Doppler echocardiographically derived S' best correlates with cardiac magnetic resonance-derived RVEF with high reproducibility and may facilitate simple and quantitative assessment of RV function.

Advanced glycation endproduct crosslink breaker (alagebrium) improves endothelial function in patients with isolated systolic hypertension.

OBJECTIVES: Arterial stiffening and endothelial dysfunction are hallmarks of aging, and advanced glycation endproducts (AGE) may contribute to these changes. We tested the hypothesis that AGE crosslink breakers enhance endothelial flow-mediated dilation (FMD) in humans and examined the potential mechanisms for this effect. METHODS: Thirteen adults (nine men, aged 65 +/- 2 years) with isolated systolic hypertension (systolic blood pressure > 140 mmHg, diastolic blood pressure < 90 mmHg or pulse pressure > 60 mmHg) on stable antihypertensive therapy were studied. Subjects received placebo (2 weeks) then oral alagebrium (ALT-711; 210 mg twice a day for 8 weeks). Subjects and data analyses were blinded to treatment. Arterial stiffness was assessed by carotid augmentation index (AI) and brachial artery distensibility (ArtD) using applanation tonometry and Doppler echo, and endothelial function by brachial FMD. Serum markers of collagen metabolism and vascular inflammation were assessed. RESULTS: Alagebrium reduced carotid AI by 37% (P = 0.007) and augmented pressure (16.4 +/- 10 to 9.6 +/- 9 mmHg; P < 0.001). Heart rate, arterial pressures, and ArtD, were unchanged. FMD increased from 4.6 +/- 1.1 to 7.1 +/- 1.1% with alagebrium (P < 0.05), and was unrelated to altered shear stress or regional arterial distensibility. However, FMD change was inversely related to markers of collagen synthesis, p-selectin and intracellular cell adhesion molecule (all P < 0.05). Alagebrium-associated changes in plasma nitrite plus nitrate was inversely correlated with plasma matrix metalloproteinase 9 and type I collagen (P = 0.007). CONCLUSIONS: Alagebrium enhances peripheral artery endothelial function and improves overall impedance matching. Improved endothelial function correlates better with reduced vascular fibrosis and inflammation markers than with vessel distensibility. AGE-crosslink breakers may reduce cardiovascular risk in older adults by reduced central arterial stiffness and vascular remodeling.

Exercise-induced hypertension, endothelial dysfunction, and coronary artery disease in a marathon runner.

Aerobic activity performed on a regular basis is 1 of several lifestyle recommendations endorsed to reduce risk of coronary disease. However, 1 potential concern of arduous aerobic activity is exercise-induced hypertension. This is the first case to our knowledge, of accelerated coronary calcification in an otherwise asymptomatic middle-aged male marathon runner devoid of traditional cardiovascular risk factors. As a consequence of exercise-induced hypertension and associated oxidative stress, improvement of endothelial dysfunction occurred after antioxidant supplementation. In conclusion, vigorous aerobic activity in susceptible individuals may promote oxidative stress and coronary atherosclerosis.

Tricuspid annular displacement predicts survival in pulmonary hypertension.

RATIONALE: Right ventricular (RV) function is an important determinant of prognosis in pulmonary hypertension. However, noninvasive assessment of the RV function is often limited by complex geometry and poor endocardial definition. OBJECTIVES: To test whether the degree of tricuspid annular displacement (tricuspid annular plane systolic excursion [TAPSE]) is a useful echo-derived measure of RV function with prognostic significance in pulmonary hypertension. METHODS: We prospectively studied 63 consecutive patients with pulmonary hypertension who were referred for a clinically indicated right heart catheterization. Patients underwent right heart catheterization immediately followed by transthoracic echocardiogram and TAPSE measurement. RESULTS: In the overall cohort, a TAPSE of less than 1.8 cm was associated with greater RV systolic dysfunction (cardiac index, 1.9 vs. 2.7 L/min/m2; RV % area change, 24 vs. 33%), right heart remodeling (right atrial area index, 17.0 vs. 12.1 cm(2)/m), and RV-left ventricular (LV) disproportion (RV/LV diastolic area, 1.7 vs. 1.2; all p < 0.001), versus a TAPSE of 1.8 cm or greater. In patients with pulmonary arterial hypertension (PAH; n = 47), survival estimates at 1 and 2 yr were 94 and 88%, respectively, in those with a TAPSE of 1.8 cm or greater versus 60 and 50%, respectively, in subjects with a TAPSE less than 1.8 cm. The unadjusted risk of death (hazard ratio) in patients with a TAPSE less than 1.8 versus 1.8 cm or greater was 5.7 (95% confidence interval, 1.3-24.9; p = 0.02) for the PAH cohort. For every 1-mm decrease in TAPSE, the unadjusted risk of death increased by 17% (hazard ratio, 1.17; 95% confidence interval, 1.05-1.30; p = 0.006), which persisted after adjusting for other echocardiographic and hemodynamic variables and baseline treatment status. CONCLUSIONS: TAPSE powerfully reflects RV function and prognosis in PAH.