Tricuspid Regurgitation Pressure Gradient Research Articles

Total bile acids levels as a stratification tool for screening portopulmonary hypertension in patients with decompensated cirrhosis.

Echocardiography is necessary for portopulmonary hypertension diagnosis, and identifying patients with cirrhosis who require it is challenging. In this study, we aimed to investigate the utility of the total bile acid (TBA) levels as a screening tool for identifying patients with decompensated cirrhosis who should undergo echocardiography for portopulmonary hypertension diagnosis. We evaluated 135 patients with decompensated cirrhosis who underwent liver transplantation. Subsequently, factors contributing to tricuspid regurgitation pressure gradient (TRPG) elevation (≥30mmHg) were analyzed using preoperative data, including the TBA levels. The median age of patients was 58years (61 women), and 45 and 90 patients had Child-Turcotte-Pugh grades of B and C, respectively. The median TRPG level was 21mmHg, and 17 patients (12.6%) showed TRPG elevation. Multiple logistic regression analysis revealed that elevated TBA (odds ratio 4.322; p=0.013) and main pulmonary artery diameter ≥33mm (odds ratio 4.333; p=0.016) were significantly associated with TRPG elevation. The TBA cut-off value (167.7μmol/L) showed a high diagnostic performance, with 70.6% sensitivity and 64.4% specificity. Ursodeoxycholic acid (UDCA) administration increased the TBA levels dose-dependently. Analysis stratified by UDCA use revealed that in patients not taking UDCA (n=59), elevated TBA levels and younger age significantly contributed to TRPG elevation. However, in those taking UDCA (n=76), this contribution disappeared, suggesting that UDCA consumption reduced TBA levels' efficiency in diagnosing TRPG elevation. The TBA levels may be a potential screening tool for TRPG elevation; however, caution is warranted when interpreting cases treated with UDCA.

Submaximal, Low-Dose Eccentric vs Traditional Cycling Exercise: Reduced Oxygen Uptake and Pulmonary Artery Pressure Assessed by Echocardiography in Healthy Middle-aged Adults. A Randomized Controlled, Crossover Trial

ObjectiveTo investigate the ventilatory and circulatory differences between eccentric (ECC) and concentric (CON) cycling exercise at submaximal, low-dose intensity from onset to end-exercise in healthy middle-aged participants. DesignRandomized controlled crossover trial. SettingThe participants underwent 1 ECC and 1 CON test according to stepwise incremental exercise protocols at identical, submaximal intensities. Breath-by-breath analyses of ventilatory gas exchange and echocardiography were used to assess cardiopulmonary function during exercise. Participants24 healthy middle-aged, untrained participants (14 women, 10 men, 50±14 years) were included. Interventions1 ECC and 1 CON test at submaximal intensities. Main Outcome MeasureThe main outcome was oxygen uptake (V'O2). ResultsThe V'O2 increase was reduced by -422 mL/min (-52%, 95% confidence interval: -513 to -292, P<.001) during ECC, as well as the ventilatory drive. Echocardiographic parameters, heart rate (-14%), cardiac output (-21%), stroke volume (-15%), and pulmonary artery pressure by tricuspid regurgitation pressure gradient (TRPG) (-26%) were also significantly reduced during ECC compared with CON at identical intensities. Participants reported significantly less dyspnea and unchanged perceived leg fatigue in ECC. ConclusionECC was well tolerated, and significant reductions were observed in V'O2, ventilation, and right ventricular load compared with CON, even at low intensity levels. This study, conducted on healthy middle-aged participants, did not raise concerns that would hinder further investigation of the effects of ECC in patients with severely limited cardiopulmonary disease, and it calls for further research on this topic.

Clinical use of macitentan in the treatment of connective tissue disease-associated pulmonary arterial hypertension.

Connective tissue disease (CTD) is the second most common cause of the pulmonary arterial hypertension (PAH). Currently, clinical data concerning CTD-PAH is scarce. Our study aimed to assess the efficacy and safety of macitentan in the treatment of CTD-PAH. In this retrospective study, patients diagnosed with CTD-PAH at The First Affiliated Hospital of Soochow University from April 2020 to November 2021 were included. Of the patients, 9 were switched to macitentan monotherapy whereas 23 received initial combination therapy. The mean follow-up time was 24 weeks. Six-minute walking distance (6MWD), World Health Organization functional class (WHO-FC), serum N-terminal pro-brain natriuretic peptide (NT-proBNP), and echocardiography parameters before and after medication were assessed. Adverse reactions were also recorded and compared. After 24 weeks of treatment, 6MWD, NT-proBNP, systolic pulmonary artery pressure (sPAP) estimated by ultrasound, tricuspid regurgitation pressure gradient (TRPG) and tricuspid annular plane systolic excursion (TAPSE) in the macitentan monotherapy group revealed significant differences (Z=-2.67, Z=-2.67, t=6.20, t=5.60, t=-3.04, P<0.05). There were no statistically significant differences in right ventricular diameter (RVD), right atrial diameter (RAD), ascending aortic root inner diameter (AAO) and left ventricular end-diastolic diameter (LVEDd) (P>0.05). After 24 weeks of medication, the number of patients with WHO-FC grade III/IV symptoms decreased from 6 to 3, 1 to 0 respectively (P<0.05), and that of patients with WHO-FC grade I/II symptoms increased from 0 to 2, 2 to 4 respectively(P<0.05). After 24 weeks of treatment, 6MWD, NT-proBNP, LVEDd, sPAP and TRPG in the macitentan combined with sildenafil treatment group revealed statistically significant differences (Z=-4.11, Z=-3.74, Z=-3.83, t=6.88, t=6.54, P<0.001). Significant differences in RVD, RAD, and TAPSE were found (t=3.46, t=3.69, t=-3.12, P<0.05). There were no statistically significant variances in AAO between the groups (P>0.05). The number of patients with WHO-FC grade III/IV symptoms decreased from 16 to 8, 5 to 0 respectively (P<0.05), and that of patients with WHO-FC grade I/II symptoms increased from 0 to 1, 2 to 14 respectively (P<0.001). There were no statistically significant differences before and after treatment in 6MWD, NT-proBNP, RVD, RAD, AAO, LVEDd, sPAP, TRPG and TAPSE between the two groups (P>0.05). There were no statistically significant differences in alanine aminotransferase (ALT), aspartate aminotransferase (AST), serum creatinine (Scr) and hemoglobin (Hb) between 0 and 24 weeks (P>0.05). Exercise tolerance and cardiac function in patients with CTD-PAH were significantly improved after treatment with macitentan, which was well tolerated. Therefore, macitentan may be an effective and safe targeted drug for CTD-PAH.

Echocardiographic Profiling Predicts Clinical Outcomes After Mitral Transcatheter Edge-to-Edge Repair.

Prior studies investigating the impact of residual mitral regurgitation (MR), tricuspid regurgitation (TR), and elevated predischarge transmitral mean pressure gradient (TMPG) on outcomes after mitral transcatheter edge-to-edge repair (TEER) have assessed each parameter in isolation. We sought to examine the prognostic value of combining predischarge MR, TR, and TMPG to study long-term outcomes after TEER. We reviewed the records of 291 patients who underwent successful mitral TEER at our institution between March 2014 and June 2022. Using well-established outcomes-related cutoffs for predischarge MR (≥moderate), TR (≥moderate), and TMPG (≥5 mm Hg), 3 echo profiles were developed based on the number of risk factors present (optimal: 0 risk factors, mixed: 1 risk factor, poor: ≥2 risk factors). Discrimination of the profiles for predicting the primary composite end point of all-cause mortality and heart failure hospitalization at 2 years was examined using Cox regression. Overall, mean age was 76.7±10.6 years, 43.3% were women, and 53% had primary MR. Two-year event-free survival was 61%. Predischarge TR≥moderate, MR≥moderate, and TMPG≥5 mm Hg were risk factors associated with the primary end point. Compared with the optimal profile, there was an incremental risk in 2-year event-rate with each worsening profile (optimal as reference; mixed profile: hazard ratio (HR), 2.87 [95% CI, 1.71-5.17], P<0.001; poor profile: HR, 3.76 [95% CI, 1.84-6.53], P<0.001). Echocardiographic profile was statistically associated with the 2-year mortality end point (optimal as reference; mixed profile: HR, 3.55 [95% CI, 1.81-5.96], P<0.001; poor profile: HR, 3.39 [95% CI, 2.56-7.33], P=0.02). The echocardiographic profile integrating predischarge TR, MR, and TMPG presents a novel prognostic stratification tool for patients undergoing mitral TEER.

Right Ventricle Strain Assessed by 2-Dimensional Speckle Tracking Echocardiography (2D-STE) to Evaluate Pulmonary Hypertension in Dogs with Dirofilaria immitis.

Echocardiographic assessment of the right ventricle is helpful for analysing the pathophysiology of heartworm disease and detecting pulmonary hypertension (PH) in dogs. In veterinary cardiology, the study of myocardial deformation using two-dimensional speckle tracking (2D-STE) echocardiography has become increasingly acknowledged as useful for quantifying right ventricular function. The aim of this study was to evaluate the usefulness of myocardial deformation strain of the right ventricular free wall (FWS), global deformation strain of the right ventricle, including the interventricular septum (GS), and tissue motion annular displacement of the tricuspid valve (TMAD) in a cohort of dogs with heartworm (Dirofilaria immitis) disease and to determine cut-off values for detecting the presence of PH. Out of the 93 dogs tested, 71% were diagnosed with heartworm infection. PH was identified in 41% of the infected dogs following the American College of Veterinary Internal Medicine (ACVIM) guidelines, based on the peak tricuspid regurgitation velocity to calculate the tricuspid regurgitation pressure gradient (TRPG), while other routine measurements were used, including the right pulmonary artery distensibility index (RPADi). The 2D-STE mode measurements were determined using Right Ventricular Automated Function Imaging (RV AFI®) software. The statistical analysis showed significant differences in the studied parameters among dogs with and without PH. Additionally, sensitivity (sen) and specificity (sp) cut-off values were obtained (GS ≥ -21.25%, sen 96%, sp 86.4%; FWS ≥ -21.95%, sen 92.56%, sp 95.5%; TMAD ≤ 0.85 cm, sen 70.4%, sp 83.3%). These results demonstrated that GS, FWS, and TMAD could be used as supplementary and alternative variables to conventional echocardiographic measurements when detecting PH in dogs with heartworm disease.

Abstract 12727: Liver Elasticity in Elderly Heart Failure Patient

Introduction: Liver elastography is a novel ultrasound technique assessing elasticity of liver tissue. Clinical indication of liver elastography remains unrevealed. Moreover, reports about relationship between liver stiffness and heart failure subtypes haven’t well been published. Hypothesis: We have investigated the cardio-hepatic interaction using liver elastography in heart failure subtypes. Methods: We prospectively enrolled 58 consecutive patients with heart failure admission from April 2022 to March 2023. Liver elastography, transthoracic echocardiography and blood sampling were done at the time of discharge from heart failure treatment. Results: Patients were divided into two groups according to the left ventricular ejection fraction (LVEF) of echocardiography: heart failure with reduced ejection fraction (HFrEF) group (EF ≦40%, n = 11) and non-HFrEF group (EF &gt;40%, n = 31). The mean age of all patients was 83 ± 11 years. The mean age and the prevalence of hypertension and diabetes mellitus was higher in non-HFrEF group than in HFrEF group. The prevalence of taking sodium glucose co-transporter 2 (SGLT2) inhibitors was lower in non-HFrEF group than in HFrEF group. LV end-diastolic diameter, LV end-systolic diameter was larger in HFrEF group than in non-HFrEF group. Tricuspid regurgitation pressure gradient (TRPG) was higher in non-HFrEF group than in HFrEF group. Inferior vena cava diameter was not different between two groups. The mean values of almost liver function tests of all patients were within the normal range. eGFR was lower in non-HFrEF group than in HFrEF group. Liver elasticity was higher in non-HFrEF group than in HFrEF group (7.1 ± 2.7 vs. 5.1 ± 1.5 hPa; P=0.008) indicating liver stiffness. Pearson’s correlation coefficient showed that liver elasticity was positively correlated with the prevalence of diabetes mellitus, LVEF, TRPG, serum creatinine, aspartate aminotransferase, γ-glutamyl transpeptidase and was negatively correlated with LV end-diastolic diameter, LV end-systolic diameter. Conclusions: Liver stiffness was elevated in EF-preserved heart failure patients. Liver elasticity was correlated with parameters of congestion (TRPG) and useful for the assessment of congestion in patients with heart failure.

Dynamic changes in echocardiographic parameters in acute decompensated heart failure: REALITY-ECHO

BackgroundAppropriate evaluation of hemodynamic status is vital in the management of acute heart failure (AHF). We aimed to investigate the changes in echocardiographic parameters during very acute phases of AHF and their association with clinical outcomes. MethodsPatients who were admitted to four Japanese hospitals with AHF were prospectively enrolled. Comprehensive echocardiography and B-type natriuretic peptide (BNP) were assessed both on admission and the second day. ResultsA total of 271 patients (80 ± 12 years old, 52 % male) was included. Overall, transmitral E velocity, E/A, tricuspid regurgitation pressure gradient (TRPG), and inferior vena cava diameter significantly decreased, and stroke volume and left ventricular ejection fraction showed a significant increase by the second day, whereas E/e′ did not change. On the second day, BNP increased in 50 patients (18 %). Despite similar baseline characteristics, patients with increased BNP showed a significantly smaller improvement in transmitral flow parameters (E and A velocity, E/A, and flow patterns) and a smaller decrease in TRPG compared with patients with decreased BNP. Other echocardiographic parameter changes were not different between the groups. A combination of improvement in transmitral flow and TRPG was significantly associated with 90-day and 1-year composite events of all-cause death and heart failure hospitalization after adjustment by the Get With the Guidelines-Heart Failure risk score. ConclusionsEchocardiographic parameters show a dynamic change in the very acute phase of AHF. Several parameters, such as the transmitral flow and TRPG might be useful in monitoring favorable hemodynamic change.

Clinical and Paraclinical Findings of Primary Pulmonary Hypertension in Children

Background: Given the significant morbidity and mortality of juvenile pulmonary arterial hypertension (PAH), understanding the clinical and paraclinical findings of this condition can aid in the early diagnosis and identification of helpful factors in its treatment. Objectives: This study aimed to evaluate the clinical and paraclinical findings of idiopathic pulmonary arterial hypertension (iPAH) in children. Methods: This cross-sectional study was carried out on 20 children with iPAH who were assessed in terms of pulmonary hypertension or hospitalized at the cardiac ward of Imam Reza hospital, Mashhad, Iran, during January 2018 to October 2001. The clinical data, chest X-ray (CXR), electrocardiographic, echocardiographic, cardiac catheterization findings, and mortality results were extracted from the medical records and recorded in a researcher-made questionnaire. Results: The current study’s findings revealed a higher prevalence of iPAH in females (70%) than men, as well as in term neonates compared to preterm newborns. The most common clinical findings were active dyspnea, heart murmur, and cyanosis. Prominent pulmonary conus, right atrial enlargement (RAE), and right ventricular hypertrophy (RVH) were the most common CXR findings. The right axis deviation, RVH, and RAE were the most common abnormal findings of electrocardiography, respectively. Based on echocardiographic findings, dilated right atrium and dilated right ventricle were reported in all subjects. The mean of tricuspid regurgitation pressure gradient (TRPG) and peak systolic pressure gradient (PSPG) were 76.33 ± 22.8 and 44.2 ± 13.18 mmHg, respectively. The mean ratios of systolic pulmonary artery pressure (PAP), diastolic PAP, and mean pulmonary artery pressure (mPAP) to aortic systolic pressure were estimated at 0.92, 0.78, and 0.88, respectively. The results confirmed a significant relationship between mPAP and consanguinity (P = 0.03). In addition, the findings demonstrated a correlation between echocardiographic findings (i.e., TRPG and PSPG) and systolic PAP, diastolic PAP, and mPAP (P &lt; 0.05). In total, 56.3% of the patients expired, most of whom (37.5%) were the younger children. Conclusions: The findings suggest that IPAH should be considered as a possible diagnosis in various clinical manifestations, including respiratory distress, hepatomegaly, ascites and even neurological symptoms. Since there are no specific symptoms, therefore a set of history, physical examination, laboratory findings, and clinical suspicion should be taken into consideration.

Prevalence of transthyretin amyloidosis among heart failure patients with preserved ejection fraction in Japan

AbstractAimsHeart failure with preserved ejection fraction (HFpEF), which is caused by wide various conditions, has become a major public health problem. Transthyretin amyloid cardiomyopathy (ATTR‐CM), which is thought to be an underdiagnosed disease, can cause HFpEF. Non‐invasive diagnosis using 99mTechnetium (Tc)‐pyrophosphate (PYP) scintigraphy enables accurate diagnosis of ATTR‐CM. The aim of this study was to clarify the prevalence and characteristics of ATTR‐CM among Japanese patients with HFpEF.Methods and resultsThis study was a multicentre, prospective, observational study conducted in Japan. We enrolled 373 patients with HFpEF [left ventricular (LV) ejection fraction ≥50%] aged ≥65 years who were admitted to the department of cardiology from September 2018 to January 2022. A 99mTc‐PYP scintigraphy scan was performed during admission in all eligible patients. Cardiac 99mTc‐PYP retention was graded according to a previously reported visual scale ranging from 0 to 3 points. The scan was considered positive when it revealed moderate‐to‐severe 99mTc‐PYP uptake (Grade 2–3) in both ventricles. Patients were divided into ATTR‐CM and non‐ATTR‐CM patients according to positive (Grade 2–3) or negative (Grade 0–1) 99mTc‐PYP scintigraphy, respectively. Medical history, blood tests, electrocardiogram, echocardiography, and magnetic resonance imaging in the two groups of patients were compared. Among the 373 patients with HFpEF, 53 patients (14.2%; 95% confidence interval: 10.7–17.7) showed positive uptake on 99mTc‐PYP scintigraphy. An endomyocardial biopsy was performed in 32 patients and confirmed amyloidosis in all cases. There were no significant differences between the two groups in age, severity of heart failure as assessed by the New York Heart Association (NYHA) functional classification, renal function values, left ventricular ejection fraction, and tricuspid regurgitant pressure gradient (ATTR‐CM, n = 53 vs. non‐ATTR‐CM, n = 320). Patients in the ATTR‐CM group had a higher N‐terminal pro‐brain natriuretic peptide level [2314 (1081–3398) vs. 900 (415–1828), P &lt; 0.001], higher sensitive troponin T level (0.074 ± 0.049 vs. 0.035 ± 0.038, P &lt; 0.001), and higher mean LV maximal wall thickness [12.5 (11–14) vs. 10.5 (9.5–11.5), P &lt; 0.001].ConclusionsATTR‐CM is an underdiagnosed disease with a significant prevalence in Japanese patients with HFpEF. This study showed that results of examinations for ATTR‐CM patients appear to be worse than those for non‐ATTR‐CM patients, but clinical severities of heart failure as assessed by the NYHA functional classification are similar in ATTR‐CM and non‐ATTR‐CM patients, and the clinical overlap between ATTR‐CM and non‐ATTR‐CM is high.

Echocardiographic Assessment of the Pulmonary Vein to Pulmonary Artery Ratio in Canine Heartworm Disease.

A total of 151 naturally heartworm-infected and 66 healthy dogs were included in the study. The presence/absence of PH was based on the right pulmonary artery distensibility index (RPAD index < 29.5%), and the PV:PA ratio was echocardiographically measured by the time-motion mode (M mode) and two-dimensional mode (2D mode). Other echocardiographic parameters were also assessed (pulmonary trunk to aorta ratio, tricuspid regurgitation pressure gradient, and AT:ET ratio). The results of the PV:PA ratio showed a highly positive correlation between the M and 2D modes (r = 0.928). The PV:PA ratio obtained by the M mode was identified as the strongest predictor for RPAD index (R2 0.628, p < 0.0001) with a good diagnostic accuracy (AUC = 0.99). The results of PV/PA by the 2D mode showed a similar prediction for the RPAD index (R2 0.606, p < 0.0001) with a good diagnostic accuracy (AUC = 0.98). Both of the 2D and M modes' PV:PA ratios decreased significantly with the presence of PH. A cut-off value of ≤0.845 showed high sensitivity and specificity for the M mode (97% and 94%, respectively) and the 2D mode (96% and 93%, respectively). The PV:PA ratio may be useful as a complementary diagnostic method for the estimation of moderate or severe PH in dogs with heartworm.

Functioning of the Human Heart in the Pron-Position.

Aim To study intracardiac hemodynamics in healthy men in supine and prone positions.Material and methods This echocardiography study included 14 apparently healthy men at a mean age of 38 years.Results In a prone position, the heart configuration and location in the chest changed, the heart rate increased by 7.3 %, and the transaortic flow velocity decreased by 13.7 %. Also, early and late right ventricular diastolic filling velocities and the pulmonary artery flow velocity were increased by 31.7, 11.4, and 5.6 %, respectively. In the intact tricuspid valve, the velocity and regurgitation pressure gradient were reduced by 7 % and 14.2 %, respectively.Conclusion In a prone position, spatial changes in the location of the heart and its structures influence velocities of intracardiac blood flow, which may initiate the development of heart failure if the prone position is long-lasting.

Long-Term Clinical Outcomes in Patients With Severe Tricuspid Regurgitation.

Background The natural history and optimal interventional timing in patients with isolated severe tricuspid regurgitation (TR) have not been well studied. This study aimed to investigate long-term clinical outcomes and risk factors associated with poor prognosis in patients with isolated severe TR. Methods and Results Consecutive transthoracic echocardiographic examinations in 2877 patients with isolated severe TR were retrospectively reviewed. Patients with significant left-sided valve disease or repeated examinations were excluded. Primary outcome was defined as a composite of all-cause death and hospitalization for heart failure. Among the 613 enrolled patients (mean age, 74±13 years; men, 38%), 141 died, and 62 were hospitalized for heart failure during the median follow-up period of 26.5 (interquartile range, 6.0-57.9) months. The 5-year event-free rate was 60.1%. TR pressure gradient (adjusted hazard ratio [HR], 1.03 [95% CI, 1.01-1.04]), blood urea nitrogen (adjusted HR, 1.02 [95% CI, 1.01-1.04]), left atrial volume index (adjusted HR, 1.01 [95% CI, 1.002-1.02]), and serum albumin (adjusted HR, 0.56 [95% CI, 0.36-0.95]) were identified as independent predictors of adverse events. A risk model based on the 4 clinical factors that included pulmonary hypertension (TR pressure gradient >40 mm Hg), elevated blood urea nitrogen levels (>25 mg/dL), decreased albumin levels (<3.7 g/dL), and left atrial enlargement (left atrial volume index <34 mL/m2) revealed a graded increase in the risk of adverse events (P<0.001). Conclusions The prognosis of isolated severe TR is not always favorable. Careful attention should be paid to patients with concomitant risk factors, such as pulmonary hypertension, elevated blood urea nitrogen levels, decreased albumin levels, and left atrial enlargement.

Tricuspid regurgitation pressure gradient to diagnose pulmonary hypertension: a diagnostic accuracy study

Background Pulmonary hypertension carries significant morbidity and mortality in children. Early diagnosis and management may improve outcomes in children with pulmonary hypertension. Heart catheterization, a gold standard for diagnosing pulmonary hypertension, is an invasive procedure and not widely available. Echocardiography can be used as an alternative diagnostic tool for pulmonary hypertension.&#x0D; Objective To determine the diagnostic value of tricuspid regurgitation pressure gradient on echocardiography compared to heart catheterization to diagnose pulmonary hypertension in children.&#x0D; Methods This diagnostic test study was done with medical record data of children with acyanotic congenital heart disease who underwent cardiac catheterization and echocardiography procedures from January 2018 to December 2020 at Dr. Sardjito Hospital, Yogyakarta, Indonesia.&#x0D; Data were analyzed to obtain sensitivity, specificity, positive and negative predictive values, as well as positive and negative likelihood ratios.&#x0D; Results A total of 98 children with acyanotic congenital heart disease were included. The sensitivity and specificity of the tricuspid regurgitation pressure gradient to determine pulmonary artery pressure compared to heart catheterization were 64.4% and 54.5%, respectively. The positive likelihood ratio was 1.42. The pre-test and post-test probability of this study were 88.7% and 91.7%, respectively.&#x0D; Conclusion Tricuspid regurgitation pressure gradient measured using echocardiography has poor sensitivity and specificity to diagnose pulmonary hypertension.

Effect of acetazolamide on pulmonary vascular haemodynamics in patients with COPD going to altitude: a randomised, placebo-controlled, double-blind trial.

COPD may predispose to symptomatic pulmonary hypertension at high altitude. We investigated haemodynamic changes in lowlanders with COPD ascending to 3100 m and evaluated whether preventive acetazolamide treatment would attenuate the altitude-induced increase in pulmonary artery pressure (PAP). In this randomised, placebo-controlled, double-blind, parallel-group trial, patients with COPD Global Initiative for Chronic Obstructive Lung Disease grades 2-3 who were living <800 m and had peripheral oxygen saturation (S pO2 ) >92% and arterial carbon dioxide tension <6 kPa were randomised to receive either acetazolamide (125-250 mg·day-1) or placebo capsules, starting 24 h before ascent from 760 m and during a 2-day stay at 3100 m. Echocardiography, pulse oximetry and clinical assessments were performed at 760 m and after the first night at 3100 m. Primary outcome was PAP assessed by tricuspid regurgitation pressure gradient (TRPG). 112 patients (68% men, mean±sd age 59±8 years, forced expiratory volume in 1 s (FEV1) 61±12% pred, S pO2 95±2%) were included. Mean±sd TRPG increased from 22±7 to 30±10 mmHg in 54 patients allocated to placebo and from 20±5 to 24±7 mmHg in 58 patients allocated to acetazolamide (both p<0.05) resulting in a mean (95% CI) treatment effect of -5 (-9 to -1) mmHg (p=0.015). In patients assigned to placebo at 760/3100 m, mean±sd S pO2 was 95±2%/88±3%; in the acetazolamide group, the respective values were 94±2%/90±3% (both p<0.05), resulting in a treatment effect of +2 (1 to 3)% (p=0.001). In lowlanders with COPD travelling to 3100 m, preventive acetazolamide treatment attenuated the altitude-induced rise in PAP and improved oxygenation.

Prevalence and implications of exercise pulmonary hypertension in chronic thromboembolic pulmonary disease

Abstract Introduction Recent international statement on chronic thromboembolic pulmonary hypertension proposed the definition of chronic thromboembolic pulmonary disease (CTEPD) and advocated further research regarding its clinical characteristic, natural history, and therapeutic strategy. Exercise pulmonary hypertension (Ex-PH) has been considered a mild degree of pulmonary hypertension (PH) among patients with normal pulmonary hemodynamics at rest. However, the clinical significance of Ex-PH in CTEPD remains unknown. Purpose In the patients with CTEPD, we aimed to verify 1) the prevalence and clinical profiles of Ex-PH, 2) effect of BPA on pulmonary vascular response after exercise in Ex-PH, 3) long-term clinical outcomes of conservative management in non-Ex-PH. Methods We retrospectively reviewed 26 patients with CTEPD (median age 65 years, 38% male), who underwent cardiopulmonary exercise test with right heart catheterization (CPET-RHC). The definitions of CTEPD are the following 1) pulmonary artery occlusion due to organic thrombus confirmed by imaging studies after ≥3 months of anticoagulation, 2) mPAP&amp;lt;25 mmHg and PAWP≤15 mmHg at rest. PQslope was plotted using multipoint plots. Ex-PH was defined by PQ slope&amp;gt;3.0, and the patients were divided into Ex-PH and non-Ex PH groups. Clinical profiles and long-term outcomes were compared between two groups. The patients in Ex-PH groupunderwent CPET-RHC 6–12 months after balloon pulmonary angioplasty (BPA). In Non-Ex-PH group, serial measurements of echocardiography were performed. Results Overall, 5 and 21 patients were categorized as CTEPD with PH (mPAP 21–24mmHg) and without PH (mPAP≤20mmHg), and 14 and 12 were categorized Ex-PH and non-Ex-PH groups, respectively. Although all 5 patients with CTEPD with PH were classified as Ex-PH group (Figure 1), there was no significant difference in baseline hemodynamics at rest between Ex-PH and non-Ex-PH groups (mPAP: 19.5 [18.4–20.6] vs. 17.7 [16.6–18.9] mmHg, PVR: 2.2 [1.7–2.7] vs. 2.3 [1.9–2.8] wood units, P&amp;gt;0.05, respectively). PQ slope was significantly higher in Ex-PH group (4.6 [3.2–6.0] vs. 1.31 [0.2–2.8], p=0.002). There were no differences in respiratory function test, blood gas analysis, and 6-minute walk distance between two groups. There were no major adverse events such as all-cause mortality and hospitalization for PH in overall cohort. Among Ex-PH group, BPA decreased PQslope (4.8 [3.6–6.4] to 2.3 [1.9–3.0], p&amp;lt;0.05). Among no-Ex-PH group, there was no significant change in tricuspid regurgitation pressure gradient (28 [17–33] to 27 [21–36] mmHg, p&amp;gt;0.05) over the 997 [651–1451] days. Conclusion Ex-PH was common in patients with CTEPD, and there were no clinical profiles differentiating Ex-PH from non-Ex-PH, except parameters of CPET-RHC. BPA improved an abnormal pulmonary vascular response to exercise in Ex-PH. The conservative management in non-Ex-PH was feasible. Randomized clinical trials will be needed to further investigate this treatment strategy. Funding Acknowledgement Type of funding sources: None.

Incremental value of myocardial work in predicting beneficial response to aortic valve replacement in patients with aortic stenosis

Abstract The predictors of favorable clinical response to aortic valve replacement (AVR) in aortic stenosis (AS) are still insufficiently defined. The increased LV afterload in AS affects the interpretation of the majority of LV systolic indices, which are load-dependent. The estimation of myocardial work (MW) is a newly developed approach, which, allowing correction of global longitudinal strain (GLS) for LV afterload, gives a more adequate insight into the intrinsic LV contractility. Aim To investigate whether the assessment of MW can improve the prediction of clinical and neurohormonal improvement post AVR in patients with AS. Methods We evaluated 126 patients (75±9 years) with severe AS who underwent transcatheter AVR (n=100) or surgical AVR (n=26). Transthoracic echocardiography, blood sampling and 6 min walk test (6MWT) were performed pre and 3 months post AVR. The following indices of MW were assessed: global work index (GWI), global constructive work (GCW), global wasted work (GWW), global work efficiency (GWE). Results Post-AVR changes in the clinical and echocardiographic profile are presented in Table. Post-treatment increase in 6MWT distance was noted in 95 patients, and decrease in NT-proBNP in 94 patients. In multivariable analysis including clinical parameters and echocardiographic indices of cardiac function, morphology and aortic valve hemodynamic, baseline GWW was the only independent echocardiographic predictor of post-AVR improvement in 6MWT distance (beta=−0.24, SE 0.09, p=0.01), whereas baseline GWE was, in addition to tricuspid regurgitation pressure gradient (TRPG) and E/e' ratio, independently associated with the post-AVR decrease in NT-proBNP (beta=0.27, SE 0.09, p=0.004). Conclusions In patients with severe AS undergoing AVR, higher values of GWW do not favor post-treatment functional improvement as assessed by 6MWT. The beneficial neurohormonal response to AVR is more pronounced in patients with less efficient LV contraction at baseline. Funding Acknowledgement Type of funding sources: None.

Right Heart Echocardiography Parameters and Other Predictors to Evaluate Mechanical Cardiac Support Necessity During Lung Transplantation

Lung transplantation (LuTx) is a challenge when right heart function fails. Mechanical circulatory support (MCS) is then necessary. We aimed to investigate whether preoperative transthoracic echocardiography (TTE) can predict MCS use and help to exclude the sickest patients. Between 2011 and 2018, 52 patients at our institution received LuTx and qualified for this study: 35 bilateral, 16 single, 1 lobar [1] and 1 retransplantation procedure. Of these, 22 were operated using MCS and 30 without MCS. The patients were aged between 18 and 65 years, and 23 were women. The indications were lung fibrosis for 18 patients, chronic obstructive lung disease for 16, cystic fibrosis for 15, primary pulmonary hypertension for 2 and bronchiectasis for 1. TTE was performed up to 30 days before treatment and 1 to 7 days after. Patients undergoing MCS versus patients not undergoing MCS: preoperative right ventricular systolic pressure 56.5 (30) vs 37.8 (11.5) mm Hg (P=.03); tricuspid regurgitation pressure gradient 48.7 (27) vs 30.2 (10.8) mm Hg (P=.015); tricuspid annular plane systolic excursion 17.8 (4.3) vs 19.9 (2.8) mm Hg (P=.04); pulmonary artery diameter 27.5 (5.2) vs 23.9 (4.1) mm (P=.004); age 41.9 (14.1) vs 54.3 (11.8) years (P=.001). Patients who were Dead versus patients who were alive pulmonary valve acceleration time of 82.8 (24.1) vs 104.9 (27.2) ms (hazard ratio [HR]=0.959, 95% confidence interval [CI]=0.923-0.996 per ms, P=.02) and pulmonary artery diameter of 28.9 (5.8) vs 24.4 (4.1) mm HR=1.225, 95% CI=1.028-1.460 per 1 mm, P=.016 were predictors of death. Preoperative TTE parameters: right ventricular systolic pressure, tricuspid regurgitation pressure gradient, tricuspid annular plane systolic excursion, and pulmonary artery diameter predicted MCS use during LuTx. Certain values of valve acceleration time and pulmonary artery diameter could help discern LuTx qualification.

The Predictability of Echocardiography in Children with Primary Pulmonary Hypertension and Its Comparison with Cardiac Catheterization Parameters

Background: Pulmonary hypertension (PH) is a serious problem with high mortality in children, so early diagnosis of this condition is critical. Echocardiography is a non-invasive hemodynamic assessment tool, which facilitates serial follow-ups for hypertensive patients. Objectives: The aim of this study was to evaluate the importance of echocardiographic parameters in children with PH and their correlation with cardiac catheterization parameters. Methods: This cross-sectional study was performed on the records of 20 children with primary PH referred to the pediatric Cardiology Department and clinic of Imam Reza Hospital, Mashhad, Iran, during 2001-2016. The correlation between echocardiography and cardiac catheterization findings was assessed to determine the predictability of echocardiographic parameters in primary pulmonary hypertension. Results: Based on the findings, the mean values of tricuspid regurgitation pressure gradient (TRPG) and peak early diastolic transpulmonary valve pressure gradient (PRPG) were 76.33 ± 22.8 and13.18 ± 44.2 mmHg, respectively. The mean of RA systolic pressure, RA diastolic pressure, RA mean pressure were 13.62 ± 4.43, 5.12 ± 2.1, and 6.77 ± 4.08, respectively. The analysis of data showed a significant correlation between systolic pulmonary artery pressure (PAP) and TRPG (r = 0.62; P = 0.008). We found no significant correlation between systolic PAP and PRPG (r = 0.58; P = 0.03). Additionally, diastolic PAP significantly correlated with TRPG (r = 0.67; P = 0.003) and PRPG (r = 0.64; P = 0.04). Moreover, a significant correlation was observed between mean PAP and TRPG (r = 0.66; P = 0.004) and PRPG (r = 0.64; P = 0.04). Conclusions: Echocardiographic approach is a safe and sensitive method for diagnosis of primary pulmonary hypertension. We found a strong correlation between mean PAP and two variables of TRPG and PRPG.

Simple algorithm to narrow down the candidates to receive echocardiography in patients with chronic liver disease for suspected pulmonary hypertension.

Portopulmonary hypertension (PoPH) is a subtype of pulmonary arterial hypertension related to portal hypertension. The definitive diagnosis of PoPH is made by invasive right heart catheterization. Alternatively, pulmonary arterial hypertension may be recognized noninvasively from the tricuspid regurgitant pressure gradient (TRPG), measured by echocardiography. In this study, we aimed to establish a simple algorithm to identify chronic liver disease patients with a high TRPG value in order to narrow down the candidates to receive echocardiography. TRPG was measured by echocardiography in 152 patients with chronic liver disease. Factors predictive of TRPG >30 mmHg were investigated. There were 28 (18%) cases with TRPG >30 mmHg. Independent factors associated with a high TRPG were the presence of shortness of breath, high serum brain natriuretic peptide (BNP), and low serum albumin. Child-Pugh class or the presence of ascites, varices, or encephalopathy was not associated with TRPG. There was a correlation between the serum BNP and TRPG, and the optimal cutoff value of BNP by the Youden index was 122 pg/mL, and by 100% sensitivity was 50 pg/mL. A combination of these factors identified patients with a high probability of TRPG >30 mmHg (n=12, positive predictive value [PPV] of 83%), no probability (n=80, PPV 0%), and intermediate probability (n=60, PPV 25-34%). This algorithm has reduced the number of patients needing echocardiography by 53%. A simple algorithm using the presence of shortness of breath, serum BNP, and albumin levels can narrow down the candidates to receive echocardiography.

Enhanced nuclear localization of phosphorylated MLKL predicts adverse events in patients with dilated cardiomyopathy.

The role of necroptosis in dilated cardiomyopathy (DCM) remains unclear. Here, we examined whether phosphorylation of mixed lineage kinase domain-like protein (MLKL), an indispensable event for execution of necroptosis, is associated with the progression of DCM. Patients with DCM (n=56, 56±15years of age; 68% male) were enrolled for immunohistochemical analyses of biopsies. Adverse events were defined as a composite of death or admission for heart failure or ventricular arrhythmia. Compared with the normal myocardium, increased signals of MLKL phosphorylation were detected in the nuclei, cytoplasm, and intercalated discs of cardiomyocytes in biopsy samples from DCM patients. The phosphorylated MLKL (p-MLKL) signal was increased in enlarged nuclei or nuclei with bizarre shapes in hypertrophied cardiomyocytes. Nuclear p-MLKL level was correlated negatively with septal peak myocardial velocity during early diastole (r=-0.327, P=0.019) and was correlated positively with tricuspid regurgitation pressure gradient (r=0.339, P=0.023), while p-MLKL level in intercalated discs was negatively correlated with mean left ventricular wall thickness (r=-0.360, P=0.014). During a median follow-up period of 3.5years, 10 patients (18%) had adverse events. To examine the difference in event rates according to p-MLKL expression levels, patients were divided into two groups by using the median value of nuclear p-MLKL or intercalated disc p-MLKL. A group with high nuclear p-MLKL level (H-nucMLKL group) had a higher adverse event rate than did a group with low nuclear p-MLKL level (L-nucMLKL group) (32% vs. 4%, P=0.012), and Kaplan-Meier survival curves showed that the adverse event-free survival rate was lower in the H-nucMLKL group than in the L-nucMLKL group (P=0.019 by the log-rank test). Such differences were not detected between groups divided by a median value of intercalated disc p-MLKL. In δ-sarcoglycan-deficient (Sgcd-/- ) mice, a model of DCM, total p-MLKL and nuclear p-MLKL levels were higher than in wild-type mice. The results suggest that increased localization of nuclear p-MLKL in cardiomyocytes is associated with left ventricular diastolic dysfunction and future adverse events in DCM.