Peak Tricuspid Regurgitation Velocity Research Articles

Effect of genotype on pulmonary hypertension risk in patients with thalassemia

Pulmonary hypertension is one of the major complications in patients with non-transfusion-dependent thalassemia (NTDT). Patients with NTDT have distinct genetic subgroups. Therefore, the effects of different genotype groups on pulmonary hypertension risk in patients with NTDT were assessed. A cross-sectional study was conducted in patients with NTDT aged ≥ 10 yr old at Srinagarind University Hospital and Udonthani Hospital, Thailand. Pulmonary hypertension risk was defined as peak tricuspid regurgitation velocity > 2.9 m/s by trans-thoracic echocardiography. Clinical characteristics and laboratory data that literature has indicated as risk factors for pulmonary hypertension were collected. The effect of genotype group on pulmonary hypertension risk was evaluated by using multivariate logistic regression analysis. Of 219 patients, pulmonary hypertension risk was found in 24 patients (10.96%). All patients were categorized into two groups according to genetic data that included: (i) β-thalassemia (139, 63.5%), (ii) α-thalassemia and combined α and β-thalassemia (80, 36.5%). Genotype groups were statistically and significantly associated with pulmonary hypertension risk based on the adjusted odds ratios after adjustment for other factors. Patients with β-thalassemia had a statistically significant higher risk for pulmonary hypertension risk (odds ratio = 9.47, P = 0.036) compared to patients with α-thalassemia and patients with combined α and β-thalassemia. The genotype group is an independent risk factor for pulmonary hypertension in patients with NTDT. Echocardiography should be routinely recommended for all patients with β-thalassemia. Routine screening in patients with α-thalassemia and combined α and β-thalassemia, however, may not be necessary or should focus on the older population.

Effects of respiration on the velocity of tricuspid regurgitation and estimation of systolic pulmonary artery pressure in patients with right ventricle systolic dysfunction

Objective. We investigated the effects of quiet respiration on the peak velocity of tricuspid regurgitation (TR) and estimation of systolic pulmonary artery pressure (SPAP) in patients with right ventricle (RV) systolic dysfunction using Doppler echocardiography. Methods. Continuous-wave Doppler spectra of TR were recorded in 32 patients with and 28 controls without RV systolic dysfunction. Electrocardiography and respiratory tracing were recorded simultaneously. Expiratory and inspiratory peak velocities of TR were acquired and averaged for five consecutive respiratory cycles. The SPAP during expiration and inspiration was calculated. Results. The velocity of TR and SPAP was not significantly different between expiration and inspiration in controls (2.77 ± 0.23 and 2.82 ± 0.26 m/s, P = 0.776; 35.94 ± 4.96 and 36.18 ± 5.12 mmHg, P = 0.747), whereas the velocity of TR and SPAP decreased significantly from expiration to inspiration in patients with RV systolic dysfunction (3.27 ± 0.35 and 2.59 ± 0.22 m/s, P < 0.001; 53.72 ± 7.39, 38.45 ± 5.63 mmHg, P < 0.001). Conclusions. Quiet respiration has significant effects on the velocity of TR in patients with RV systolic dysfunction. This factor should be taken into account when using Doppler echocardiography to estimate these patients’ SPAP, and the measurements should be performed in patients at the end of expiration.

Echocardiographic assessment of right heart indices in dogs with elevated pulmonary artery pressure associated with chronic respiratory disorders, heartworm disease, and chronic degenerative mitral valvular disease

The aim of this study was to evaluate right ventricular (RV) remodeling and right heart failure associated with different causes of elevated pulmonary arterial pressure (PAP) in dogs. In total, 169 client-owned dogs with tricuspid regurgitation (TR) and 40 client-owned clinically healthy dogs were included. Dogs with TR were further categorised as suffering from chronic respiratory disorders (CRD), heartworm disease (HWD), mild/moderate chronic degenerative mitral valvular disease (CDMD), and severe CDMD. Among the echocardiographic indices of the right heart, no significant difference in the tricuspid annular plane systolic excursion to aortic root diameter ratio was found among the clinical healthy controls and the four different TR categories. No significant differences in TR peak velocity and pulmonic regurgitation peak velocity were found among dogs in the four different TR categories. The ratio of the right to left ventricular basal diameter in the right ventricular-focused view was significantly higher in dogs with chronic respiratory disorders and dogs with heartworms. Left ventricular compression quantified using the eccentricity index and the ratio of the main pulmonary artery to aortic root diameter were significantly higher in dogs with HWD. Their right ventricular acceleration to ejection time (AT/ET) was significantly lower in dogs with HWD. Based on these findings, we conclude that right heart indices are affected by CRD, HWD, and moderate to severe CDMD. However, right heart indices derived from left heart measurements might be underestimated in dogs with CDMD.

Pressure reflection in the pulmonary circulation by echocardiography in patients with left heart disease indicates reactive pulmonary hypertension

Background and aims: The two hemodynamic profiles in Left Heart Disease (LHD) with Pulmonary Hypertension (PH), passive PH with increased pulmonary venous pressure and reactive PH with increased Pulmonary Vascular Resistance (PVR), cannot be distinguished non-invasively. We hypothesized that echocardiographic signs of Pressure Reflection (PR) in the pulmonary circulation can be used to diagnose reactive PH. Methods: The study comprised 122 patients that were divided into three groups: patients without PH (No PH, n=61), patients with PH (pulmonary artery mean pressure, PAMP≥25 mmHg) and normal PVR (Passive PH, n=29) and patients with increased PVR (Reactive PH, n=32). Echocardiography and Right Heart Catheterization (RHC) was performed within 24 hours. Three PR variables were selected: the acceleration time in the Right Ventricular Outflow Tract (RVOT), the time interval between RVOT peak velocity and peak tricuspid regurgitant velocity and the right ventricular pressure increase after peak RVOT velocity. Separate cutoff values indicating either high likelihood (major criteria) or low likelihood (minor criteria) for PVR>3WU were investigated using Receiver Operator Characteristic (ROC) curves. Results: The mean±SD age was 50±14 years, and the percentage of males was 63%. Sixty-eight patients (56%) underwent RHC due to known or suspected LHD whereof 23 patients had dilated cardiomyopathy. Thirty-one patients (25%) were heart transplant recipients, 8 patients (7%) had cardiac amyloidosis and 15 patients (12%) were miscellaneous. No patient included in the study had PH or increased PVR due to other causes than left ventricular dysfunction. Sixty-six percent of patients with Reactive PH had mild to moderate PH (PAMP 25-40 mmHg). The proportion of patients with pulmonary capillary wedge pressure>15 mmHg was 14% in No PH, 97% in Passive PH and 74% in Reactive PH. The area under the ROC curve for PR variables was 0.82 to 0.89. With three major criteria present the likelihood of PVR>3 WU increases 27.3 fold (positive likelihood ratio) and absence of minor criteria decreases the likelihood 8.3 fold (negative likelihood ratio). Conclusions: Echocardiographic assessment of PR in patients with LHD can be used to identify or exclude reactive PH. Patients with reactive PH often have mild to moderate rather than severe PH.

Can echocardiography discriminate between pulmonary arterial hypertension and pulmonary hypertension related to left heart disease in patients with cardiovascular risk factors?

Purpose: As the prevalence of cardiovascular risk (CV) factors is increasing by age, the diagnosis of pulmonary arterial hypertension (PAH) is becoming more challenging. The purpose of this study was to assess whether transthoracic echocardiography may help to differentiate between PAH and pulmonary hypertension (PH) related to left heart disease (PH-LHD) in PH patients with CV factors before cardiac catheterization. Methods: We retrospectively studied consecutive incident PH patients at a single centre between 01 January 2008 and 15 July 2011. All patients underwent cardiac catheterization. We selected those who had at least one of the following CV factors: systemic hypertension, type 2 diabetes mellitus, permanent atrial fibrillation, coronary artery disease, obesity or mitral and/or aortic disease. We divided the patients into two groups: a PAH group (PAH-CV) and a PH-LHD group. After Bonferroni correction the statistical threshold shifted to 0.001 level. Results: The results are shown in Table 1. View this table: Table 1. Comparison of echocardiographic features Conclusions: 1. In PHLHD left atrial and ventricular dimensions are greater than in PAH 2. In PAH the right ventricle expands at the expense of the left ventricle 3. In PAH tricuspid regurgitation peak velocity is higher and pericardial effusion is more common. These differences show the potentially helpful role of echocardiography in discrimination between PAH and PH-LHD in patients with PH and CV factors.

Prognostic significance of tricuspid regurgitation peak velocity in patients with heart failure and preserved ejection fraction

Prognostic significance of tricuspid regurgitation peak velocity in patients with heart failure and preserved ejection fraction

Pulmonary arterial hypertension

Pulmonary arterial hypertension (PAH) is a chronic and progressive disease leading to right heart failure and ultimately death if untreated. The first classification of PH was proposed in 1973. In 2008, the fourth World Symposium on PH held in Dana Point (California, USA) revised previous classifications. Currently, PH is devided into five subgroups. Group 1 includes patients suffering from idiopathic or familial PAH with or without germline mutations. Patients with a diagnosis of PAH should systematically been screened regarding to underlying mutations of BMPR2 gene (bone morphogenetic protein receptor type 2) or more rarely of ACVRL1 (activine receptor-like kinase type 1), ENG (endogline) or Smad8 genes. Pulmonary veno occusive disease and pulmonary capillary hemagiomatosis are individualized and designated as clinical group 1'. Group 2 'Pulmonary hypertension due to left heart diseases' is divided into three sub-groups: systolic dysfonction, diastolic dysfonction and valvular dysfonction. Group 3 'Pulmonary hypertension due to respiratory diseases' includes a heterogenous subgroup of respiratory diseases like PH due to pulmonary fibrosis, COPD, lung emphysema or interstitial lung disease for exemple. Group 4 includes chronic thromboembolic pulmonary hypertension without any distinction of proximal or distal forms. Group 5 regroup PH patients with unclear multifactorial mechanisms. Invasive hemodynamic assessment with right heart catheterization is requested to confirm the definite diagnosis of PH showing a resting mean pulmonary artery pressure (mPAP) of ≥ 25 mmHg and a normal pulmonary capillary wedge pressure (PCWP) of ≤ 15 mmHg. The assessment of PCWP may allow the distinction between pre-capillary and post-capillary PH (PCWP > 15 mmHg). Echocardiography is an important tool in the management of patients with underlying suspicion of PH. The European Society of Cardiology and the European Respiratory Society (ESC-ERS) guidelines specify its role, essentially in the screening proposing criteria for estimating the presence of PH mainly based on tricuspid regurgitation peak velocity and systolic artery pressure (sPAP). The therapy of PAH consists of non-specific drugs including oral anticoagulation and diuretics as well as PAH specific therapy. Diuretics are one of the most important treatment in the setting of PH because right heart failure leads to fluid retention, hepatic congestion, ascites and peripheral edema. Current recommendations propose oral anticoagulation aiming for targeting an International Normalized Ratio (INR) between 1.5-2.5. Target INR for patients displaying chronic thromboembolic PH is between 2–3. Better understanding in pathophysiological mechanisms of PH over the past quarter of a century has led to the development of medical therapeutics, even though no cure for PAH exists. Several specific therapeutic agents were developed for the medical management of PAH including prostanoids (epoprostenol, trepoprostenil, iloprost), endothelin receptor antagonists (bosentan, ambrisentan) and phosphodiesterase type 5 inhibitors (sildenafil, tadalafil). This review discusses the current state of art regarding to epidemiologic aspects of PH, diagnostic approaches and the current classification of PH. In addition, currently available specific PAH therapy is discussed as well as future treatments.

Elevated mean pulmonary artery pressure in patients with mild-to-moderate mitral stenosis: a useful predictor of worsening renal functions?

Renal dysfunction commonly accompanies the course of cardiac disorders and strongly associates with increased morbidity and mortality. Elevated central venous pressure is related to worsening renal function in patients with heart failure. However, predictors of worsening renal function in mitral stenosis-whose pathophysiologic process is similar to heart failure with regard to right heart dysfunction-are unknown. This study aimed to evaluate whether clinical and echocardiographic parameters might predict worsening renal function in patients with mild-to-moderate mitral stenosis. The current study has a prospective cohort design. Sixty consecutive patients (9 male, 51 female, mean age 50±13 years) with mild-to-moderate mitral stenosis were followed up for 34±13 months (range 1-60) and their renal functions were monitored. Worsening renal function was defined as a decline in glomerular filtration rate of ≥ 20% on follow-up. In order to presence or absence of worsening renal functions, study patients divided into two groups. Statistical analysis was performed using the Chi-square, Independent samples t / Mann-Whitney U tests, univariate and multivariate Cox proportional hazards analyses, receiver operating characteristic (ROC) and Kaplan-Meier curve analyses. Worsening renal function was observed in 14 patients (23%). In univariate analysis, male gender, mean pulmonary artery pressure (mPAP), peak tricuspid regurgitation velocity, systolic pulmonary artery pressure, digitalis and antiplatelet usage, right atrial size, and TEI index were determined to be predictors of worsening renal function. In a multivariate Cox proportional hazards model, mPAP (HR=1.136, 95% CI: 1.058-1.220, p<0.001) and male gender (HR=4.110, 95% CI: 1.812-9.322, p=0.001) were associated with increased risk of worsening renal function during the follow-up period. In ROC curve analysis, the optimal cut-off value of mPAP to predict worsening renal function was measured as more than 21 mmHg, with 78.6% sensitivity and 58.7% specificity (AUC 0.725, 95% CI 0.595-0.838). According to the Kaplan-Meier curve, a significant difference was found between those who had mPAP of >21 mmHg, and those who did not have, in terms of worsening renal function (p=0.006), and the difference between the groups increased after 30 months of follow-up. Elevated mean pulmonary artery pressure at the time of initial evaluation, in patients with mild-to-moderate mitral stenosis, might help to predict worsening renal function.

ASSA13-10-3 The Value of Colour Doppler Echocardiography in the Elderly During the Procedure of Patent Ductus Arteriosus Occlusion

<h3>Background</h3> To investigate the value of colour Doppler echocardiography (CDE) in the closure of patent ductus arteriosus (PDA) in the elderly. <h3>Methods</h3> Before the occlusion, screening the indicantions for twenty-five elderly patients with PDA by CDE. Using the shunt flow signal of colour Doppler flow imaging (CDFI) to estimate the pulmonary side diameter of PDA, compare with the angiocardiography and determine its accuracy through statistics. Using the continuous wave Doppler (CW) to measure peak velocity of tricuspid regurgitation and estimate cross-tricuspid pressure gradient according to the simplified Bernoulli equation ΔP = 4V², together with the inherent right atrial pressure to estimate pulmonary artery pressure. Then compare cross-tricuspid pressure gradient and pulmonary artery pressure with cardiac catheterization. Determine its accuracy through statistics. All patients underwent interventional therapy and determine the efficacy of occlusion by CDE. <h3>Results</h3> all the occlusion of the elderly patients with PDA was successful through the examination by CDE. The diameter of the PDA pulmonary side estimated by the shunt flow signal had a positive correlation with angiocardiography (r = 0.71, P &lt; 0.001). Pulmonary artery pressure estimated by the CW had a positive correlation with cardiac catheterization contrast (r = 0.63, P &lt; 0.001). <h3>Conclusions</h3> CDE has an important value in the elderly during the procedure of patent ductus arteriosus occlusion. Using CDFI to estimate PDA pulmonary side diameter and CW to estimate pulmonary artery pressure before the occlusion is the key to screen the indication of occlusion. And it is also important for using CDFI to observe whether there was a residual PDA shunt after transcatheter closure.

ASSESSMENT OF MARKEDLY ELEVATED PULMONARY VASCULAR RESISTANCE BY ECHOCARDIOGRAPHY

The ratio of peak tricuspid regurgitation velocity to the time velocity integral of the right ventricular outflow tract (TRV/TVIRVOT) distinguishes elevated versus normal invasive pulmonary vascular resistance (PVRcath). We aim to validate TRV/TVIRVOT as a correlate of PVRcath and compare TRV/

PULMONARY VASCULAR RESISTANCE: A NOVEL METHOD OF NON-INVASIVE ESTIMATION AND ASSOCIATION WITH MORTALITY IN CRITICALLY ILL SURGICAL PATIENTS

Doppler-derived ratio of peak tricuspid regurgitant velocity (TRV, ms) to the right ventricular outflow tract time velocity integral (TVIRVOT, cm) is a reliable non-invasive method of estimating pulmonary vascular resistance (PVR). The easier to measure left ventricular outflow tract time velocity

A rabbit model of right-sided Staphylococcus aureus endocarditis created with echocardiographic guidance

BackgroundThe most widely used experimental models of infective endocarditis (IE) are the rabbit and rat models, in which cardiac valve lesions are induced by a polyethylene catheter introduced into the left ventricle through the aortic valve. Our study was designed to create a rabbit model of IE right-sided with echocardiographic guidance.MethodsThirty rabbits underwent both catheterization and inoculation (group A). These were divided into three subgroups of ten based on the time of catheter removal (immediately, after 24 h, and after death or moribundity for groups, A1, A2, and A3, respectively). Ten inoculated-only and ten catheterized-only rabbits served as controls. A catheter system consisted of a polyethylene catheter and a guide wire inside it. This system was passed through the rabbits’ tricuspid valves under echocardiographic guidance to damage them. The ratio of left ventricle to right ventricle (LV/RV) was measured in a four-chamber view before catheterization and at the time of death or moribundity. The peak velocity of tricuspid regurgitation (VTR) was measured in a four-chamber view at the time of catheterization and at the time of death or moribundity. Staphylococcus aureus (ATCC 29213) inoculation was performed 24 h after right heart catheterization to produce IE.ResultsIE was confirmed in 28 of 30 rabbits by macroscopic and histologic examination of tricuspid valves, blood cultures, and bacterial count in cardiac vegetations. Cardiac vegetations were confirmed in 25 of 28 IE rabbits by echocardiography. Enlargement of right ventricle dimension with a significantly decreased LV/RV ratio was confirmed in all IE rabbits at the time of death or moribundity than at the initial state (1.11 ± 0.35 vs. 1.95 ± 0.39, P < 0.01; 1.21 ± 0.34 vs. 1.98 ± 0.35, P < 0.01; 1.04 ± 0.31 vs. 2.00 ± 0.41, P < 0.01 for groups A1, A2, and A3, respectively). VTR was significantly higher in all the IE rabbits at the time of death or moribundity than at the time of catheterization (1.89 ± 0.46 vs 0.76 ± 0.45, P < 0.01; 2.04 ± 0.73 vs 0.68 ± 0.66, P < 0.01; 2.24 ± 0.51 vs 0.87 ± 0.55, P < 0.01 for group A1, A2 and A3, respectively).ConclusionThe models described herein closely reproduced the pathogenesis and pathophysiology of right heart catheter-induced endocarditis in humans. Echocardiographic guidance is helpful in the process of right heart catheterization. Some echocardiographic parameters, such as VTR and the LV/RV ratio could be used to assess the success or failure of the IE models.

4D flow-sensitive MR estimation of pulmonary vascular resistance

Background Pulmonary arterial hypertension (PAH) is characterized by progressive increase in pulmonary vascular resistance (PVR), leading to right ventricular (RV) failure [1]. PVR is calculated using right heart catheterization (RHC), from the trans-pulmonary pressure gradient (ΔP) and pulmonary flow (QPA). Doppler echocardiography can estimate PVR from the ratio of peak tricuspid regurgitation velocity (TRV) to main pulmonary artery velocity time-integral (MPA flow) [2]. MRI is increasingly used to assess right ventricular (RV) function in PAH. Determining PVR from MRI could enable a more complete characterization of RV and PA interactions in PAH. The purpose of this study was to non-invasively estimate PVR from TRV/QPA using a 4D flow-sensitive MRI sequence in humans [3]. Methods Six PAH patients referred for right heart catheterization (RHC) and six healthy volunteers were scanned according to an IRB-approved protocol. In patients, RHC was performed clinically within 1 week of the MRI in patients with PAH. PVRRHC was calculated as follows: PVR=ΔP/QPA. 4D flow MRI (Phase Contrast with Vastly undersampled Isotropic Projection Reconstruction - PC VIPR) was performed on 3T clinical scanners (GE Healthcare, Waukesha, WI) after the administration of gadolinium-based contrast agents. PC VIPR parameters: FOV=32 x 32 x 22 cm, isotropic 1.3 mm spatial resolution, TR/TE = 6.3/2.1 ms, Venc=150 cm/s, scan time: ~10 min using respiratory and retrospective ECG gating. Post-processing was done using Ensight (CEI, Apex, NC) and MatLab (The Mathworks, Natick, MA) to measure peak TRV and QPA. Statistical analysis included regression analysis to evaluate the correlation between TRV/QPA and PVRRHC. Ar egression equation was derived to calculate PVRMRI. Differences between PVRMRI and PVRRHC were assessed using Bland-Altman analysis. TRV/QPA ratios in healthy controls were compared to those in PAH patients using Student t-test. Results Average (± standard deviation) PVRRHC was 7.15 ± 3.56 UW. The Pearson correlation coefficient between TRV/QPA and PVRRHC was 0.94. The equation derived from linear regression was PVRMRI = 0.69*PVRRHC 2.84 UW. Using this equation, the average (± standard deviation) PVRMRI was 7.15 ± 3.35 (p=0.99). The mean difference between PVRMRI and PVRRHC was 0 with positive and negative levels of agreement of 2.4 and -2.4, respectively. Differences in TRV/QPA in healthy controls and PAH patients were statistically significant (p=0.0003).

Noninvasive assessment of elevated pulmonary vascular resistance in children with pulmonary hypertension secondary to congenital heart disease: A comparative study between five different Doppler indices

BackgroundPulmonary vascular resistance (PVR) is an important hemodynamic parameter in patients with congenital heart disease (CHD). Noninvasive estimation of PVR represents an attractive alternative to invasive measurements. MethodsThe study included 175 patients with pulmonary hypertension (PH) secondary to CHD. All patients underwent full echocardiographic study and invasive hemodynamic measurements. The study population was then subdivided into four subgroups. Each of the following Doppler indices was measured in one of these four subgroups: peak tricuspid regurgitant velocity (TRV), the ratio of the TRV to the velocity time integral of the right ventricular outflow tract (TRV/TVIRVOT), peak velocity of tricuspid annular systolic motion (TSm), heart rate corrected acceleration time and infliction time of the proximal left pulmonary artery (ATc, InTc). The data obtained was correlated with invasive PVR measurement. An ROC curve analysis was done to generate cutoff points with the highest balanced sensitivity and specificity to predict PVR>6WU/m2. The receiver operating characteristics (ROC) curves were compared with each other to determine the most reliable cutoff point in predicting elevated PVR>6WU/m2. ResultsThere was a significant correlation between both the TRV and TSm and invasive measurement of PVR (r=−0.511, 0.387 and P value=0.0002, 0.006 respectively). The TSm and TRV cutoff values were the most reliable to predict elevated PVR>6 WU/m2. A TSm cutoff value of ⩽16.16cm/s provided the best balanced sensitivity (85.7%) and specificity (66.7%) to determine PVRCATH>6 WU/m2. A cutoff value less than 7.62cm/s had 100% specificity to predict PVRCATH>6 WU/m2. A TRV cutoff value of >3.96m/s provided the best balanced sensitivity (66.7%) and specificity (100%) to determine PVRCATH>6 WU/m2. Both TRV and TSm had the highest area under the ROC curve among the 5 DOPPLER indices studied. ConclusionPrediction of elevated PVR in children with PH secondary to CHD could be achieved noninvasively using a number of Doppler indices. Among the five Doppler indices examined in the current study, the peak TRV and the TSm of the lateral tricuspid annulus had the highest balanced sensitivity and specificity to predict PVRI>6 WU/m2.

Estimation of Pulmonary Vascular Resistance: Correlation between Echocardiography and Catheterization Data in Patients with Congenital Heart Disease

The ratio of peak tricuspid regurgitation velocity (TRV) and right ventricular outflow time-velocity integral (TVI RVOT) has been described as a good correlate of pulmonary vascular resistance (PVR). However, this method has not been well studied in congenital heart disease. Twenty patients with post-tricuspid shunt lesions who were planned to undergo cardiac catheterization were enrolled for the study. The ratio of TRV/TVI(RVOT) was measured via transthoracic echocardiography and correlated with invasively derived PVR (PVR(CATH)). PVR(CATH) was measured by cardiac catheterization. Fick's principle was used to calculate the pulmonary blood flow and oxygen consumption was assumed. Linear regression analysis was done to find the correlation between TRV/TVI(RVOT) and PVR(CATH). There was a significant correlation between the two variables, r = 0.635(P = 0.003). Subgroup analysis revealed that this correlation was better at lower values of PVR(CATH) (r = 0.817 for PVR < 6 Wood units (WU)) than higher values (r = 0.659 for PVR > 6 WU). TRV/TVI(RVOT) ratio of greater than 0.145 predicted with 80% sensitivity and specificity a PVR > 6 WU. There is modest correlation between TRV/TVI(RVOT) ratio and invasively derived PVR in congenital shunt lesions, especially in PVR < 6 WU. TRV/TVI(RVOT) ratio could be useful in identifying patients with congenital shunts whose PVR is likely to be <6 WU, and hence, do not need cardiac catheterization.

Integration of Genomic and Genetic Approaches Highlight a Novel Validated Gene Signature for Pulmonary Hypertension Associated with Sickle Cell Disease

Abstract 511 Background:Pulmonary hypertension (PH) is a serious complication of sickle cell disease (SCD) associated with increased mortality. Gene expression profiles of peripheral blood mononuclear cells (PBMC) and genetic strategies have been studied in pulmonary arterial hypertension and in SCD. We hypothesized that a PBMC-derived gene signature in SCD patients may be utilized as a PH biomarker which may be further validated using integrated genomic and genetic strategies. Methods & Results: Twenty-seven patients with homozygous SCD underwent transthoracic echocardiography and PBMC isolation for genome—wide expression profiling. An independent SCD cohort (n=132) was genotyped using Affymetrix 6.0 SNP array and also underwent TTE. PH was defined as estimated right ventricular systolic pressure (RVSP)>30 mmHg with a peak tricuspid regurgitation velocity (TRV)>2.5m/s. Genome-wide mRNA and miRNA expression profiles were correlated against PH severity using RVSP (correlation coefficient ρR) and TRV (ρT) as surrogates. Utilizing a correlation threshold (ρR2>0.15, ρT2>0.15) for prioritization yielded 631 transcripts and 12 miRNAs. A support vector machine analysis on the transcripts identified a 10 gene signature which discriminated patients with and without echo-defined PH with 100% accuracy. This gene signature was then validated in an independent cohort of SCD patients with PH confirmed by right heart catheterization (n=10) and without PH (n=10) with 90% accuracy. In silico analyses of the top PH-related miRNAs revealed strong binding predictions of miR-301a to polypeptide N-acetylgalactosaminyltransferase 13 (GALNT13), a PH signature gene, which was further validated by microarray data confirming correlation between miR-301a and GALNT13 expression (p=0.024). Genome-wide association study in 132 adult SCD patients comparing echo-defined PH (n=51) versus no PH (n=81) revealed 12 significant SNPs, which were within or upstream to the PH signature genes (Table 1, P<0.01). Seven of the 12 SNPs were associated with GALNT13, further validating this top candidate PH signature gene. Integrating all available genomic and genetic information from a sub-population of 24 patients with SCD revealed significant expression quantitative trait loci (eQTLs) associated with echo-defined PH. Within our PH signature genes, we found four trans-acting eQTLs, based on a FDR<5% with Bonferroni-Holm correction (p=2.1 e-07 for all four) and 1 cis-acting eQTL (p=0.6e-04) upstream of the adenosine A2B receptor gene (ADORA2B) based on a nominal p value 1e–03. Conclusion: These genomic signatures are potential biomarkers to screen at-risk populations in SCD for the presence of PH. Integrative analyses with genomic and genetic analyses highlight ADORA2B and GALNT13, a glycosyltransferase enzyme, as potential candidate genes in SCD-related PH.Table ITop SNPs associated with PH signature genes and echo-defined PHSNPPH Signature GeneMinor AlleleMinor Allele FrequencyP ValueOdds RatioFrequency- SCD PH casesFrequency- SCD controlsPositionrs799813GALNT13G0.20730.00090.28040.1020.277Intronicrs6701513PREFLPG0.26520.00202.3740.36270.2037Upstreamrs4664705GALNT13T0.36640.00282.2380.470.3025Upstreamrs10920634PREFLPT0.35980.00352.2170.4510.3025Upstreamrs16851575PREFLPC0.3750.00470.44890.29410.4259Upstreamrs2794452PRELPC0.46150.00490.47330.34310.538Upstreamrs4664706GALNT13A0.36740.00652.0710.46080.3086Upstreamrs7603830GALNT13A0.42370.00700.48280.320.4877Upstreamrs799761GALNT13G0.49620.00941.9630.5980.4321Intronicrs16834781GALNT13T0.20.010.37130.11960.25Intronicrs16834331GALNT13A0.13640.010.32230.068630.179Upstreamrs3818943PREFLPG0.47350.010.50070.4020.5185Upstream Disclosures:No relevant conflicts of interest to declare.

Deterioration of Mitral Valve Competence After the Repair of Atrial Septal Defect in Adults

Although mild mitral regurgitation (MR) associated with atrial septal defect (ASD) is believed to improve by ASD closure alone, new-onset MR or aggravation of preexisting mild MR may also develop after ASD closure. We sought to determine the preoperative risk factors for the postoperative deterioration of mitral valve competence in adults with ASD. Retrospective review of 286 adults with ASD who had undergone surgical closure of ASD between January 2004 and December 2009 was performed. Patients with significant preoperative MR (≥III/IV) that necessitated mitral valve intervention were excluded. Preoperative MR grades were 0 in 204 patients, I in 67 patients, and II in 15 patients. After ASD repair, MR degree did not change or improved in most of the patients (204 of 286, 71%), whereas 82 patients (82 of 286, 29%) showed aggravated or new-onset MR, including 18 patients whose MR degree increased by grade 2 or more. Univariable analysis revealed older age, preoperative atrial fibrillation, large left atrial size, large indexed ASD size, high peak tricuspid regurgitation velocity, and associated tricuspid valve surgery or Maze procedure as risk factors for new-onset or aggravated MR, but only older age (odds ratio, 1.058; 95% confidence interval, 1.025 to 1.092; p = 0.0005) and indexed ASD size (odds ratio, 1.120; 95% confidence interval, 1.042 to 1.205; p = 0.0022) remained significant on multivariable analysis. The ratio of postoperative left ventricular end-diastolic volume to preoperative left ventricular end-diastolic volume was greater in patients with new-onset or aggravated MR (p = 0.016). Mitral valve competence may deteriorate after ASD closure in older patients with large ASD.

Echo Doppler Predictors of Pulmonary Artery Hypertension in Patients with Systemic Sclerosis

Evaluate echocardiographic predictors of pulmonary artery hypertension (PAH) in a prospective cohort of patients with systemic sclerosis (SSc). 38 patients with SSc who did not have PAH and significant left heart disease, with peak tricuspid regurgitant velocity (TRV) ≤ 2.8 m/sec and systolic pulmonary artery pressure (sPAP) < 40 mmHg on echo Doppler were enrolled. Patients underwent: clinical assessment, NT-proBNP, and DLco measurements. Echo Doppler evaluation included right ventricular (RV) dimensions, tricuspid annular plan systolic excursion, fractional area change, tricuspid DTI systolic velocity, Tei index, pulmonary flow acceleration time (AcT), ratio of TRV to RV outflow tract time-velocity integral (TVI) and a parameter of disturbed RV ejection (TRV/AcT). After a planned 12-month follow-up we evaluated the predictive value of these parameters for the development of PAH, as demonstrated by right heart catheterization (RHC). Criteria for RHC were TRV ≥ 3 m/sec or sPAP ≥ 40 mmHg. Four patients developed PAH. Only TRV/TVI and TRV/AcT ratios significantly predicted PAH development (TRV/TVI ratio ≥ 0.16 [predefined and ROC confirmed]: OR 99, CI 95%: 4.865-2015, P = 0.004; TRV/AcT ratio ≥ 0.022 [predefined and ROC confirmed]: OR 12.68, CI 95% 1.163-379.3, P = 0.036). Both parameters showed a good diagnostic power (TRV/TVI ratio: ROC area 79%, sensitivity 75%, specificity 97% and diagnostic accuracy 94.74% for cutoff value of 0.16; TRV/AcT ratio: ROC area 75%, sensitivity 75%, specificity 71% and diagnostic accuracy 72% for cutoff value of 0.022). This prospective study identified increased values of the two ratios TRV/TVI and TRV/AcT as predictors of PAH in SSc.

Range of right heart measurements in top-level athletes: The training impact

ObjectivesTo explore the full range of right heart dimensions and the impact of long-term intensive training in athletes. BackgroundAlthough echocardiography has been widely used to distinguish the athlete's heart from pathologic left ventricular (LV) hypertrophy, only few reports have described right ventricular (RV) and right atrial (RA) adaptations to extensive physical exercise. Methods650 top-level athletes [395 endurance- (ATE) and 255 strength-trained (ATS); 410 males (63.1%); mean age 28.4±10.1; 18–40years] and 230 healthy age- and sex-comparable controls underwent a transthoracic echocardiographic exam. Along with left heart parameters, right heart measurements included: RV end-diastolic diameters at the basal and mid-cavity level; RV base-to-apex length; RV proximal and distal outflow tract diameters; RA long and short diameters; and RA area. Tricuspid annular plane systolic excursion and RV tissue Doppler systolic peak velocity were assessed as indexes of RV systolic function. Pulmonary artery systolic pressure (PASP) was estimated from the peak tricuspid regurgitant velocity. ResultsATS showed increased sum of wall thickness and relative wall thickness, whereas left atrial volume, LV end-diastolic volume, LV stroke volume and PASP were significantly higher in ATE. RV and RA measurements were all significantly greater in ATE than in ATS and controls. ATE also showed improved early diastolic RV function, whereas RV systolic indexes were comparable among groups. On multivariate analysis, type and duration of training (p<0.01), PASP (p<0.01) and LV stroke volume (p<0.001) were the only independent predictors of the main RV and RA dimensions in athletes. ConclusionsThis study delineates the upper limits of RV and RA dimensions in highly-trained athletes. Right heart measurements were all significantly greater in elite endurance-trained athletes than in age- and sex-matched strength athletes and controls. This should be considered as a “physiologic phenomenon” when evaluating athletes for sports eligibility.

Pulmonary Artery Acceleration Time Provides an Accurate Estimate of Systolic Pulmonary Arterial Pressure during Transthoracic Echocardiography

Transthoracic echocardiographic estimates of peak systolic pulmonary artery pressure are conventionally calculated from the maximal velocity of the tricuspid regurgitation (TR) jet. Unfortunately, there is insufficient TR to determine estimated peak systolic pulmonary artery pressure (EPSPAP) in a significant number of patients. To date, in the absence of TR, no noninvasive method of deriving EPSPAP has been developed. Five hundred clinically indicated transthoracic echocardiograms were reviewed over a period of 6 months. Patients with pulmonic stenosis were excluded. Pulsed-wave Doppler was used to measure pulmonary artery acceleration time (PAAT) and right ventricular ejection time. Continuous-wave Doppler was used to measure the peak velocity of TR (TR(Vmax)), and EPSPAP was calculated as 4 × TR(Vmax)(2)+ 10 mm Hg (to account for right atrial pressure). The relationship between PAAT and EPSPAP was then assessed. Adequate imaging to measure PAAT was available in 99.6% of patients (498 of 500), but 25.3% (126 of 498) had insufficient TR to determine EPSPAP, and 1 patient had significant pulmonic stenosis. Therefore, 371 were included in the final analysis. Interobserver variability for PAAT was 0.97. There were strong inverse correlations between PAAT and TR(Vmax) (r= -0.96), the right atrial/right ventricular pressure gradient (r= -0.95), and EPSPAP (r= -0.95). The regression equation describing the relationship between PAAT and EPSPAP was log(10)(EPSPAP)= -0.004 (PAAT)+ 2.1 (P < .001). PAAT is routinely obtainable and correlates strongly with both TR(Vmax) and EPSPAP in a large population of randomly selected patients undergoing transthoracic echocardiography. Characterization of the relationship between PAAT and EPSPAP permits PAAT to be used to estimate peak systolic pulmonary artery pressure independent of TR, thereby increasing the percentage of patients in whom transthoracic echocardiography can be used to quantify pulmonary artery pressure.