Pulmonary Systolic Pressure Research Articles

9 The Burden of Bronchopulmonary Dysplasia and Pulmonary Vascular Disease in Premature Infants

Abstract Primary Subject area Neonatal-Perinatal Medicine Background Extremely premature infants are at a high risk of bronchopulmonary dysplasia (BPD) and BPD-associated pulmonary hypertension (PH). Prolonged patency of the ductus arteriosus (PDA) may worsen PH; however, due to the lack of evidence supporting improvement in outcomes after strategies to promote ductal closure, our center has adopted a strict non-intervention policy since 2013. Objectives Assess PH prevalence and severity, as well as the impact of BPD on echocardiographic parameters of cardiac performance. Design/Methods Retrospective cohort of infants <29 weeks gestational age at birth, admitted between 2015 and 2019, and without genetic/congenital anomalies. Measurements from the echocardiography acquired closest to 36 weeks were done by masked experts. Severe BPD was defined as positive pressure support at 36 weeks. PH was defined as an estimated systolic pulmonary pressure (SPAP) ≥40 mmHg or an abnormal septal curvature by eccentricity index (EI) (>1.3). Results Out of 387 infants, 222 were included, of which 27 (12%) were categorized as severe BPD and 78 (35%) had PH. Severe BPD was associated with lower birth weight (704±214 vs 842±229g, p<0.01), longer hospitalization (median 138 [IQR 108-167] vs 103 [IQR 86-125] days, p<0.01) and longer mechanical ventilation duration (median 82 [IQR 33-107] vs 17 [IQR 2-32] days, p<0.01), with no difference in gestational age at birth. Severe BPD was associated with PH (70% vs 43%, p<0.01). The combined outcome of death (after the 36 weeks echocardiography) or severe BPD was associated with PH (68% vs 30%, p<0.01), smaller left ventricle length in diastole (2.8±0.5 vs 3.0±0.5 cm, p=0.03), decrease in the tricuspid annular plane systolic excursion (0.7±0.2 vs 0.9±0.2 cm, p<0.01), abnormal EI (1.31±0.25 vs 1.17±0.18, p<0.01) and smaller right ventricle fraction area change (41.3±5.8 vs 47.8±7.6%, p<0.01), without a significant increase on SPAP (35±21 vs 35±14, p=0.15). Other echocardiographic markers were similar. Conclusion In the context of a PDA non-intervention policy, a third of our population was affected by PH at 36 weeks. Furthermore, those with severe BPD or death had signs of RV dysfunction (despite similar SPAP estimate), indicating that the effect of BPD on pulmonary vascular remodelling and cardiac function may be underestimated.

Stress echocardiography and outcomes after cardiac surgery in patients with ischemic mitral regurgitation

Abstract Background Ischaemic mitral regurgitation (IMR) is a frequent complication of coronary artery disease. This is generally associated with double mortality rates. Poor prognosis could be observed despite successful cardiac surgery. There is a gap about predictors of further negative outcomes after surgical treatment. Owing to the dynamic nature of IMR, we hypothesize that multiparametric stress echocardiography (SE) would be helpful in assessing risk stratification. Aim: To evaluate the relationship between multiparametric SE parameters and outcomes after cardiac surgery in patients with IMR. Methods We prospectively enrolled 30 patients (62.7±8.5 yrs, 18 men), who have severe IMR by ESC classification, referred for coronary artery bypass grafting (CABG) with or without mitral surgery. Before cardiac surgery, the patients performed semi-supine bicycle multiparametric SE. Wall motion abnormalities, systolic and diastolic volumes of left ventricle, B-lines (lung congestion feature), left atrium volume, pulmonary pressure, mitral regurgitation volume, and effective regurgitation orifice area (EROA) were assessed before and during exercise. Ejection fraction (EF) and left contractile reserve were calculated. All-cause death was an endpoint. Results All patients had indications for CABG due to severe three-vessel disease. Before exercising, EF was 42±12%, end-diastolic volume was 167±49 ml, systolic volume of left ventricle was 86±39 ml, left atrium was 103±37 ml, global longitudinal strain was 12±4%, index of wall motion abnormality was 1.83±0.48, EROA was 0.39±0.22 cm2, regurgitation volume was 58±27 ml, systolic pulmonary pressure was 43±16 mmHg, and B-lines were 2.4±2. During exercise, EF was 44±17%, end-diastolic volume was 148±54 ml, systolic volume of left ventricle was 98±44 ml, index of wall motion abnormality was 2.30±0.49, EROA was 0.45±0.2 cm2, regurgitation volume was 70±32 ml, systolic pulmonary pressure was 51±14 mmHg, and B-lines were 5.4±3.3. A median follow-up time was 332 days (224–335). ROC analysis demonstrated that left ventricle end-diastolic volume during exercise (the cut-off value 192 ml, area under the ROC curve 0.77, p<0.03), EROA during exercise (the cut-off value 0.37 cm2, the area 0.86, p<0.0003), regurgitant volume during stress (the cut-off value 82 ml, the area 0.79, p<0.02), the difference between stress and rest B-lines (the cut-off value 6 lines, the area 0.83, p<0.0001), the difference between stress and rest EROA (the cut-off value 0.15 cm2, the area 0.77, p=0.05) were associated with death. Conclusion The stress echocardiographic parameters were associated with increased mortality after cardiac surgery in patients with IMR over the 1-year follow-up. B-lines (objective evidence of severe congestive heart failure), EROA, regurgitation volume (severity of mitral regurgitation during exercise) were all associated with worse outcome. These preliminary results should be confirmed in the larger studies. Funding Acknowledgement Type of funding sources: None.

Infective endocarditis after transcatheter aortic valve implantation

Abstract Introduction Infective endocarditis (IE) is a potentially serious complication in patients with prosthetic heart valves. The objective of this study is to analyze and describe the incidence, baseline characteristics, risks factors and in-hospital evolution in IE after Transcatheter Aortic Valve Implantation (IE-TAVI). Methods All the TAVI implanted in our center since the beginning of the program have been included consecutively. Patients with a confirmed diagnosis of IE according to the “ESC Guidelines for the management of infective endocarditis” are identified and analyzed. Results 331 TAVI have been implanted in our center from June 2009 to February 2021. IE-TAVI incidence in our series is 2.7% (n=9 cases). In baseline analysis, we observed that insulin dependent diabetes mellitus, Barthel Score and Pulmonary systolic pressure >50mmHg are significantly associated with the appearance of IE-TAVI (TABLE 1). The most frequently microorganism is Enterococcus faecalis (44.4%; n=4) followed by Staphylococcus aureus (22.2%; n=2), Coagulase-negative staphylococci (22.2%; n=2) and Streptococcus viridans (11.1%; n=1). 77.8% of IE-TAVI (n=7) are Nosocomial IE or non-nosocomial healthcare-associated IE. 2 of them have been related to implantation (1 Enterococcus faecalis and 1 Coagulase-negative staphylococci) and 5 have been related to other interventions (2 after gastroscopy, 1 after percutaneous vascular intervention, 1 hemodialysis catheter infection and 2 unknown focus). 44.4% of IE-TAVI (n=4) were confirmed after performing Positron Emission Tomography (PET) scan. 3 cases (33.3%) were diagnosed with the initial Transthoracic Echocardiogram (TTE) and 2 cases (22.2%) were diagnosed after performing a Transesophageal Echocardiogram (TEE) (TABLE 2) 4 patients had an indication for surgery according to the ESC Guidelines (3 for persistent bacteremia and 1 for severe aortic regurgitation), but all were ruled out due to high surgical risk. Hospital mortality was 44.4% (n=4). The main predictor of hospital mortality was having an indication for surgery (p=0.028), which was present in 3 of the 4 deaths. The other death was due to digestive bleeding during hospitalization. Conclusions IE-TAVI is a serious disease with high in-hospital mortality. Insulin dependent diabetes mellitus, Barthel Score and Pulmonary systolic pressure >50mmHg are risk factors for IE-TAVI. PET-scan is the imaging test of choice when there were no echocardiographic findings. The main predictor of mortality is having an indication for surgery according to the ESC Guidelines. Funding Acknowledgement Type of funding sources: None.

Idiopathic pericardial effusion in patients with hypertrophic cardiomyopathy

The aims of this study were to examine the prevalence of moderate to large (moderate–large) idiopathic pericardial effusion (i-PEF) in patients with hypertrophic cardiomyopathy (HCM) and to identify clinical and echocardiographic hemodynamic profiles associated with pericardial effusion. A total of 292 adult patients with HCM were studied. Fifteen patients with a history of factors associated with pericardial effusion including myocardial infarction, heart surgery or cardiac procedure within the last 12 months, autoimmune disease, hydralazine use, chronic kidney disease stage 3–4, tuberculosis, and malignancy were excluded. Of 277 eligible patients with HCM, 11 patients (4%) with moderate-large i-PEF were identified. Clinical tamponade was present in 1 patient. Compared to patients with HCM who had no or small pericardial effusion, patients with moderate-large i-PEF were younger and more likely to have right ventricular (RV) hypertrophy and reverse septal curvature. These patients also exhibited a greater maximal septal thickness, mean and systolic pulmonary pressure, and right atrial pressure (p < 0.05 for all). Pericardial fluid analysis and histopathological exams were performed in 7 and 3 patients, respectively. All examinations revealed transudative and nonspecific etiology of pericardial effusion. Idiopathic pericardial effusion and cardiac tamponade in patients with HCM was uncommon. The pathophysiology involved in pericardial effusion remains undetermined. Patients with moderate-large i-PEF frequently exhibited a phenotype of pulmonary hypertension and RV pressure overload.

Global constructive myocardial work predicts left ventricular disfunction onset beyond longitudinal strain in patients with significant primary mitral regurgitation

Abstract Accurate surgical timing for significant primary mitral regurgitation (PMR) still remains an issue despite of several ways of left ventricular (LV) hidden disfunction detection, including LV global longitudinal strain (GLS). Since novel modalities such as myocardial work (MW) or area strain (AS) are currently available we assumed that they might predict surgical timing beyond known parameters. Methods 58 patients (31 female) 63±8 years, asymptomatic and with pulmonary systolic pressure (PSP) ≤45 mmHg on exercise echo test (ET), with PMR, in sinus rhythm, with ejection fraction (EF) ≥65% and GLS &amp;lt;−19.5% were enrolled into the study along with 23 healthy subjects matched by age and sex and followed up for 1 year. Comprehensive echocardiography (EchoCG) was performed with offline analysis including MW and AS by one experienced specialist. GW index (GWI) was obtained from pressure-strain loops derived from speckle tracking analysis multiplied by brachial systolic blood pressure.Global constructive work (GCW) as the sum of positive work due to myocardial shortening during systole and negative work due to lengthening during isovolumic relaxation, global wasted work (GWW) aa energy loss by myocardial lengthening in systole and shortening in isovolumic relaxation, and GW efficiency (GWE) as the percentage ratio of constructive work to the sum of constructive work and wasted work were obtained by the dedicated software. Results 13 (22%) patients with PMR became symptomatic or increase PSP &amp;gt;50 mmHg on ET in 1 year follow up. EF, GLS, AS and GWI did not differ between symptomatic patients and those who remained asymptomatic during follow up, however these patients had significantly lower values of GCW, and higher values of GWW (EF 68.3±6.1% vs 69.2±6.5%, p=NS; GLS –22.4±2.3% vs 23.1±3.2%, p=NS, GWI 2452±161 mmHg% vs 2479±147 mmHg%, p=NS; GCW 1875±119 mmHg% vs 2321±124 mmHg%, p&amp;lt;0.01; GWW 118±9 mmHg% vs 88±7 mmHg%, p&amp;lt;0.03; GWE 93±8% vs 96±9%, p=NS; AS −32.5±5.4% vs −34.3±6.1%, p=NS;). Patients with subsequent symptoms development had significantly lower values of GCW and higher values of GWW. Among all parameters GCW was the predictor of MR clinical course worsening (AUC 0.769). Conclusion MR GCW is able to predict clinical course of patients with PMR beyond known conventional parameters. Funding Acknowledgement Type of funding sources: Public Institution(s). Main funding source(s): City Hall resources

Peritoneal dialysis as a therapeutic solution in elderly patients with cardiorenal syndrome and heart failure: a case-series report

Abstract Background The aim of this work was to evaluate the impact of peritoneal dialysis (PD) on venous congestion, right ventricle function, systolic arterial pulmonary pressure and clinical functional status in elderly patients with cardiorenal syndrome (CRS) and chronic heart failure (HF). Methods A case series of 21 (17 males, 70±11 years) consecutive pts with diuretic-resistance heart failure and right ventricular dysfunction (median renal failure duration (RF) 60 months, range 13–287 months, mean ejection fraction 36±11%) having been engaged in PD (median of 12.5 months, range 2–28); 77% of the pts were under Automated Peritoneal Dialysis (APD), whereas the rest were under Continuous Ambulatory PD (CAPD). Patients' Pulmonary Artery Systolic Pressure (PASP), Central Venus Pressure (CVP) – through compression sonography – and body weight were evaluated in 6 intermediate clinical visits. Results During the follow-up period, the mortality rate was 8 deaths out of 21 pts (38%) (or 3 deaths/100 person-months).A significant reduction by 29.9% in PASP levels (p=0.013)and by 42% in CVP levels (p&amp;lt;0.001), and in right ventricular function was observed; whereas pts weight increased by 3.7% (p=0.001). NYHA class improved in 12 pts; whereas, in the rest pts remained constant (p=0.046). In 8 pts complications were reported (mainly presence of staphylococcus. aureus). Conclusion PD seems to confer a substantial benefit in clinical status, in line with improvement in venous congestion and right ventricle systolic pressure among elderly HF patients with CRS. Funding Acknowledgement Type of funding sources: None.

Impact of right ventricular dysfunction after MitraClip treatment as a bridge to heart transplantation: insights from the MitraBridge registry

Abstract Background MitraClip treatment has been recently proposed as a “bridge strategy” solution for advanced heart failure (HF) patients with significant functional mitral regurgitation (MR), who are potential candidates or are waiting for cardiac replacement therapy (LVAD or heart transplantation, HTx). In this clinical scenario, left-ventricular-related right ventricular dysfunction (RVD) represents an important prognostic factor. Purpose Our study aimed to investigate the possible prognostic implication of RVD in advanced HF patients treated with MitraClip as a bridge to HTx strategy. Methods RVD was assessed using the relationship between tricuspid annular peak systolic excursion (TAPSE) and pulmonary artery systolic pressure (PASP). All patients from the MitraBridge registry for whom these two echocardiographic parameters were available, were included in the study. A cut-off value of TAPSE/PASP ratio &amp;lt;0.36 was used to defined RVD, as previously reported. The primary outcome was a composite end-point of all-cause death or rehospitalization for HF at 2-year. For patients who underwent LVAD implantation or HTx, follow-up data were censored at the time of those events. Results A total of 80 patients were included in the study. The median TAPSE/PASP ratio was 0.35 (25th-75th: 0.27–0.46), with 43 (54%) patients having a TAPSE/PASP ratio &amp;lt;0.36 (RVD group). The latter had a prevalent MR ischemic etiology (49% vs 38%), with a more frequent history of percutaneous coronary intervention (46.5% vs 22%, p=0.02). Except for TAPSE (15.7±3.6 mm vs 19.2±3.7 mm, p=0.001) and PASP (61±14 mmHg vs 39.5±9.5 mmHg, p&amp;lt;0.001), the other echocardiographic characteristics were similar between the two study groups (overall mean left ventricular ejection fraction 26.9±8%, median left ventricular end-diastolic volume index 120.7, 25th-75th: 102.2–146.5 mL/m2). After a median follow-up time of 508 (25th-75th: 160–899) days, elective HTx occurred in 12 patients (7 from the RVD group), while LVAD implantation was performed in 13 patients (7 from the RVD group). The primary outcome occurred in 30 patients (38%) with a 2-year Kaplan-Meier estimate of freedom from the composite end-point of 41%. At univariate (HR 1.3 95% CI 0.6–2.8, p=0.451) and multivariate (HR 1.6 CI 0.7–3.8, p=0.249) Cox-regression analysis, TAPSE/PASP ratio &amp;lt;0.36 was not identified as an independent predictor of primary outcome. Indeed, at follow-up echocardiographic control (median time 252, 25th-75th: 122–365 days), a significant improvement in TAPSE/PASP ratio was observed in the RVD group (baseline median TAPSE/PASP ratio 0.27, 25th-75th: 0.22–0.32 vs follow-up median TAPSE/PASP ratio 0.37, 25th-75th: 0.28–0.47, p&amp;lt;0.001). Conclusion In advanced HF patients with functional MR, MitraClip treatment could prevent or ameliorate left-ventricular-related RVD, allowing safe access to HTx or LVAD. Funding Acknowledgement Type of funding sources: None.

Three-month cardiac outcomes of survivors of COVID-19 presenting to a district general hospital in West Hertfordshire, UK

Abstract Background COVID-19 is novel entity associated with significant morbidity and mortality. Most patients recover completely, however, a proportion describe persistent symptoms consistent with cardiopulmonary disturbance. The long-term cardiac and respiratory outcomes of COVID-19 are not known. Purpose The aim of this study was to undertake a comprehensive cardiopulmonary assessment of survivors of COVID-19 with post recovery symptoms. The cardiac findings are presented here. Methods Survivors of COVID-19 presenting to a general hospital in West Hertfordshire between 18 March 2020 and 15 May 2020, were reviewed at 3 months using a structured prespecified protocol. Patients with persistent symptoms and those admitted to the intensive care unit (ICU) were invited to attend a clinical assessment comprising an electrocardiogram (ECG), echocardiography, chest x-ray (CXR) and pulmonary function tests. At follow up, patients were categorised according to disease course: 1) monitored via a community based virtual hospital, 2) admitted for supplemental oxygen, 3) requiring non-invasive ventilation and 4) ICU admission. Results 448 eligible patients were evaluated by telephone. 11 patients admitted to ICU and 147 patients with persistent symptoms were invited for further assessment. At presentation, hospitalised patients were older, had higher levels of obesity and increased rates of hypertension than those managed virtually (p&amp;lt;0.05). Among hospitalised patients, the degree of pulmonary infiltration on CXR was higher, ROX index for intubation lower, eGFR lower, C-reactive protein levels higher and lymphocyte counts lower, compared to those managed virtually (p&amp;lt;0.05). The prevalence of known respiratory conditions was higher among patients admitted to hospital, with a trend towards statistical significance (p=0.051). There were no differences in the prevalence of known cardiac disorders and other co-morbidities amongst both patient groups (table 1). At follow up, CXR appearances were improved and similar among patients monitored virtually, those admitted for supplemental oxygen, those requiring non-invasive ventilation and those treated on ICU. There were no differences in heart rhythm and ECG parameters in the four patient groups. Left ventricular systolic and diastolic dimensions, Simpson's biplane ejection fraction, left atrial volume and left ventricular filling pressures were similar in all four patient groups. There were no differences in right ventricular dimensions, right ventricular fractional area change, tricuspid annular plane systolic excursion and pulmonary artery systolic pressures among patients irrespective of disease severity (table 2). Conclusions At 3 months, we identified no differences in ECG indices and echocardiographic parameters of left and right ventricular function among survivors of COVID-19, independent of disease course. The findings of this study argue against significant cardiac sequalae following COVID-19 infection. Funding Acknowledgement Type of funding sources: None.

Clinical outcome after MitraClip procedure: role of right ventricle

Abstract Background MitraClip system is a device for percutaneous edge-to-edge repair of the mitral valve in symptomatic patients with severe mitral regurgitation (MR) not eligible for surgery, but frequently heart failure symptoms remain substantial on mid-term follow-up. Recently, right ventricular (RV) to pulmonary arterial (PA) coupling has emerged as a relevant prognostic predictor in heart failure but little is known about its prognostic role in patients after MitraClip implantation. Purpose To identify echocardiographic predictors of clinical outcome after MitraClip procedure, with a particular focus on RV-PA coupling. Methods We retrospectively analyzed the data of patients with severe MR who underwent MitraClip implantation between April 2015 and October 2019 at our Institution. Echocardiographic data were assessed at baseline, 3 and 12 months after the procedure; RV to PA coupling was assessed using the ratio between tricuspid annular plane systolic excursion (TAPSE) and pulmonary artery systolic pressure (PASP). Functional class was assessed at 12 months of follow-up. Significance level was set to 0.05 and SPSS was used for statistical analysis. Results 41 patients were included (age 77.1±7.3, 71% male, BMI 25.8±5.5). MR was primary, functional and mixed in 22, 76 and 2% of patients, respectively. 1/2/3 mitraclips were implanted in 39/56/5% of patients, respectively. Echocardiographic data at baseline, at 3 and 12 months follow-up are shown in Table. NYHA class at 12 months significantly correlated with TAPSE and PASP at 3 months follow-up echocardiogram (beta coefficient −0.83 and 0.78 respectively). On the contrary, NYHA class did not show a correlation with left ventricular ejection fraction (LVEF) or residual MR grade. At 12 months 44% of patients showed an improvement in NYHA class; these patients had a better TAPSE (22.7±1.3 vs 19.4±4.6 mm), a lower PASP (37.9±10.2 vs 48.5±12.9 mmHg) and a better TAPSE/PASP (0.61±0.2 vs 0.42±0.2) compared to patients who did not improve their functional class, while LVEF and residual MR did not differ. Conclusion In this sample of significant MR undergoing repair with MitraClip System, patients with functional class improvement at 12 months follow-up showed a better RV-coupling without difference in LV function and residual MR. Funding Acknowledgement Type of funding sources: None. Table 1

The right ventricular-pulmonary circulation coupling in ischaemic heart disease; a stress echocardiography study

Abstract Objectives This study sought to assess the right ventricular (RV) - pulmonary circulation coupling in patients with coronary artery disease (CAD), preserved echocardiographic indices of right ventricular systolic function and normal pulmonary artery systolic pressure (PASP). Background Patients with CAD are at increased risk for developing left, and ultimately right heart failure. The analysis of underlying mechanisms of worsening RV function has been limited to the hemodynamic sequelae of increased left ventricular (LV) filing pressure leading to pulmonary hypertension. It has been reported that evaluation of RV functional state by using the tricuspid annular plane systolic excursion (TAPSE)/PASP ratio as a surrogate for the RV length-force is of clinical prognostic relevance in patients with known pulmonary hypertension; its role has not been extensively explored in other cardiac conditions including myocardial ischaemia. We hypothesized that the TAPSE/PASP ratio may be able to identify early and subtle changes in RV function in patients with CAD, normal estimated resting PASP, and preserved TAPSE. Methods Data were obtained from a prospectively maintained database, and 223 consecutive patients with preserved right ventricular systolic function (TAPSE≥16mm), and normal resting PASP (≤35mmHg), undergoing stress echocardiography (SE) for suspected coronary artery disease were included. Exclusion criteria: non-ischaemia study, severe valvular disease, poor image quality, resting pulmonary hypertension, reduced right ventricular systolic function. Transthoracic 2-D Doppler echocardiogram was performed by an accredited sonographer at rest and during stress phase and reviewed by two cardiologists unaware of clinical data. Results Fifty-three (24%) SE studies were positive for ischaemia and 170 (76%) negative. Demographic characteristics of both groups are shown in Table 1. All patients had TAPSE≥16mm and a PASP≤35mmHg as per inclusion criteria. The mean TAPSE/PASP ratio was significantly lower in patients with a positive SE suggestive of CAD than controls (0.84±0.22 vs 0.93±0.24, P=0.024). The TAPSE/PASP ratio showed significant correlation with the maximum workload (Watts) achieved (r=0.17, P=0.015) and exercise time (min) (r=0.15, P=0.031), and an inverse correlation with age (r=−0.26, P&amp;lt;0.001) and the development of inducible exertional breathlessness (Exp(B) 0.11, 95% CI 0.028–0.457, P=0.002) on SE. Conclusion Resting TAPSE/PASP was reduced in patients with positive SE, compared to controls. Indexing RV function to RV load, with the use of the TAPSE/PASP ratio identified early changes in RV-pulmonary circulation coupling in CAD patients without resting pulmonary hypertension; this may denote the beginning of subclinical RV dysfunction. Funding Acknowledgement Type of funding sources: None. Table 1

The thromboxane receptor antagonist NTP42 improves haemodynamics, inhibits remodelling, and restores function within the cardiopulmonary system in preclinical pulmonary arterial hypertension models

Abstract Background Pulmonary arterial hypertension (PAH) is a rare and fatal disease characterised by a progressive increase of pulmonary artery pressure leading to right heart failure. While current PAH therapies provide symptomatic relief and some improvement in quality of life, they show limited benefit in preventing disease progression and often have severe side effects. Recent studies by us reported that a novel thromboxane A2 receptor (TP) antagonist NTP42 attenuated multiple disease hallmarks of PAH in two preclinical models of the disease. Purpose The aim of this study was to assess the efficacy of a novel oral formulation of NTP42 developed for pharmaceutical use on monocrotaline (MCT)-induced PAH in rats across a range of cardiopulmonary parameters, and when compared with standard of care (SOC) PAH therapies. It also aimed to evaluate the expression of the TP, the target receptor for NTP42, in tissues from the MCT-induced PAH model and related disease models. Methods PAH was induced by subcutaneous injection of 60 mg/kg MCT. Rats were randomly assigned to 7 groups: (1) No MCT; (2) MCT Only; (3) MCT+NTP42 Formulation (1 mg/kg); (4) MCT+Sildenafil (50 mg/kg); (5) MCT+Macitentan (30 mg/kg), (6) MCT+Selexipag (1 mg/kg), and (7) MCT+Riociguat (5 mg/kg), where in all cases twice-daily oral dosing was initiated 7 days post-MCT and continued for 22 days. Results The results show that the formulated NTP42 reduced the severity of MCT-induced PAH as determined from haemodynamic measurements of mean pulmonary artery pressure (mPAP) and right ventricular systolic pressure (RVSP), Fulton's Index of cardiac hypertrophy and histological assessments of pulmonary vascular remodelling, pulmonary oedema, inflammation and fibrosis, and right ventricular fibrosis. In addition, these assessments showed that NTP42 inhibited these effects at least to a similar extent relative to the SOC drugs Sildenafil, Macitentan, Selexipag and Riociguat. Notably, unlike most of the PAH SOCs, NTP42 had no adverse effects on liver weight and or on hepatic histopathology. Importantly, NTP42 had no effects on either the systemic mean arterial pressure (mAP) or heart rate (HR). Furthermore, while abundant expression of the target TP was noted in numerous cell and tissue types of both cardiac and pulmonary tissue, there were highly significant upregulations of TP expression observed following PAH-induction (RV, &amp;gt;2-fold, p=0.0002). Conclusions Taken together, these data demonstrate that NTP42 significantly attenuates MCT-induced PAH and to a similar or greater extent relative to market leader PAH SOC drugs. Notably, we reveal that expression of the TP, the target receptor for NTP42, was shown to be highly significantly upregulated throughout the cardiopulmonary system, validating the potential importance of this largely ignored PAH target ripe for pharmaceutical intervention. Funding Acknowledgement Type of funding sources: Public grant(s) – EU funding. Main funding source(s): EU Horizon 2020 SME Instrument

Comparative efficacy and safety of mycophenolate mofetil and azathioprine in combination with corticosteroids in the treatment of lymphocytic myocarditis

Abstract Purpose To compare of the efficacy and safety of mycophenolate mofetil (MM) and azathioprine in combination with corticosteroids in the treatment of lymphocytic myocarditis. Methods The study included 45 patients with lymphocytic myocarditis, 34 male, the average age 48.1±11.2 years. The diagnosis of myocarditis is verified by endomyocardial biopsy. In ten patients of both groups, the parvovirus B19 DNA was detected in the myocardium. All patients had heart failure 3 [3; 3] NYHA class. High immune activity was indicated by the presence of anti-heart antibodies in all patients. Group 1 included twenty-six patients who received MM 2 g per day. Twenty of them were naive; six patients received MM instead of azathioprine, which was canceled due to cytopenia and/or insufficient effect. Group 2 included nineteen patients who received azathioprine at an average dose of 100 [75; 150] mg per day. Patients of both groups also received methylprednisolone in an average starting dose 24 [24; 32] mg per day and standard therapy for heart failure. Initial group distribution was random. Patients in both groups did not differ significantly in baseline parameters. The mean follow-up period was 23 [8; 57] months (12 and 34 months in the groups). The study is approved by the university ethics committee. Results The level of anti-heart antibodies significantly decreased in both groups. In both groups there was a significant improvement in the structural and functional parameters of the heart: NYHA class decreased from 3 [2.75; 3] to 2 [1; 2] (group 1, p&amp;lt;0.001) and from 3 [3; 3] to 2 [1; 2] (group 2, p&amp;lt;0.001), LV EF increased initially from 30.6±7.8 to 40.1±7.5% (group 1, p&amp;lt;0.001) and from 27.9±8.1 to 37.1±7.6% (group 2, p&amp;lt;0.01), by the end of follow-up to 45.9±9.0% (group 1, p&amp;lt;0.001) and to 42.4±13.7% (group 2, p&amp;lt;0.01). LV EDD significantly decreased from 6.4±0.6 to 6.1±0.8 cm (p&amp;lt;0.01), left atria size from 4.9±0.7 to 4.3±0.6 cm (p&amp;lt;0.05) and pulmonary arteria systolic pressure from 37.8±12.3 to 29.3±7.6 (p&amp;lt;0.05) only in the group 1. No direct side effects of MM were noted. Cytopenia due to treatment of azathioprine developed in 3 patients and required its replacement. There were no significant differences between groups 1 and 2 in overall mortality (7.7 vs 15.8%) and the transplant + death rate (7.7 vs 21.1%). The better survival in the MM group may be due to a shorter follow-up period. Conclusion In patients with lymphocytic myocarditis, a combination of moderate doses of corticosteroids with MM is at least no less effective and safe than steroids with azathioprine. With a shorter follow-up period, the tendency to lower mortality and a more pronounced improvement in structural parameters with better tolerance was noted in the MM group. MM should be considered as an alternative option in the treatment of isolated lymphocytic myocarditis. Funding Acknowledgement Type of funding sources: None.

Assessment of mitral valve area by 3D planimetry after percutaneous mitral valve repair

Abstract Background Percutaneous mitral valve (MV) repair has become an effective therapeutic alternative to MV surgery in high-risk surgical patients with severe MR. Persistent pulmonary hypertension after mitral valve replacement has shown an increased risk of morbidity and mortality. Improvement of pulmonary systolic arterial pressure (PSAP) post-MitraClip has been reported, however relative mitral stenosis may hamper this benefit. Few data is available regarding the best echocardiographic parameter to determine mitral stenosis after the procedure. Purpose To evaluate the correlation between the residual mitral valve area (MVA) by 3D planimetry, the pressure half time (PHT) and the transmitral gradient after percutaneous edge-to-edge mitral repair. Methods This is a single-center, retrospective study. We enrolled 88 consecutive patients who underwent a percutaneous MV repair with the MitraClip system between 2010 and 2020 at our tertiary university hospital, with eligibility evaluation by transesophageal echocardiogram (TEE). All patients had moderate to severe (3+) or severe (4+) primary or secondary MR. Results The mean age was 76.2±10.4 years and 64.8% of the patients were male. Above 88% of patients were in New York Heart Association class III/IV. Baseline 3D planimetry MVA was 5.3±1.4cm2 and mean gradient pre-implantation was 1.8±0.8mmHg. After the procedure, MVA reduced to 2.9±0.8cm2 and mean gradient was 2.8±1.4mmHg. Both 3D planimetry and mean gradient were very significantly correlated (r −0.5; p&amp;lt;0.001) (Figure 1), whereas no correlation was note between mean gradient and PHT (r 0.17; p=0.117) Conclusion After MitraClip implantation, the assessment of mitral valve area by 3D planimetry is significantly correlated with the transmitral mean gradient, unlike PHT. Funding Acknowledgement Type of funding sources: None. Figure 1. Correlation of post-procedural 3D MVA and transmitral mean gradient

Myocardial injury in stress echocardiography: comparison of dobutamine, dipyridamole and dynamic stress echocardiography – single centre study

Abstract Background Stress echocardiography (SE) plays important role in investigation of the patients with chest pain. Adverse events rate is higher in dobutamine stress echocardiography on comparison to dobutamine stress echocardiography (ExSE) or dipyridamole stress echocardiography (DIP). Dynamic stress (ExSE) is recommended as the first-choice method according to the current guidelines. Purpose Response to the different stressors was studied in several studies with controversial results. This study aimed to investigate myocardial injury during stress echocardiography measured by the serum high sensitivity troponin (hsTnT) in a low risk population and whether there is a difference in hsTnT response between various stressors. Methods 135 patients (DSE n=46, ExsE n=46, Dip n=43) investigated for chest pain with suspicion on angina with negative diagnostic stress echocardiography were enrolled in the study. HsTnT was measured before and at 180 min. after the test was terminated. Patients with baseline elevated hsTnT levels (≥14 pg/ml), impaired LV EF (&amp;lt;50%), regional wall motion abnormalities, previous acute coronary syndrome and/or revascularisation, known epicardial coronary artery stenosis &amp;gt;50%, diabetes, prediabates (fasting glycemia at the day of the test ≥5,6 mmol/l, left ventricle hypertrophy &amp;gt;13 mm, baseline uncontrolled hypertension (BP &amp;gt;160/100 mmHg), estimated systolic pulmonary pressure &amp;gt;45 mmHg, more than moderate valvular disease, and patient who experienced dobutmine side effect (hypotension, atrial fibrillation) were excluded from the study. Results HsTnT increased in DSE and ExSE, but not in DIP group [9,4 (1,5–58,6), 1,1 (−0,9–15,7), −0,1 (−1,4–2,1) ng/L, p&amp;lt;0,001]. Similar result was found In DSE and ExSE subgroups without atropine [5,3 (0,4–45,3) vs 1,1 (−1,1–15,7) ng/L, p&amp;lt;0,001]. Adding atropine during SE triggered much greater hsTnT release in DSE [40,1 (3,7–160,3) vs 5,3 (0,4–45,3) ng/L, p&amp;lt;0,001], but not in ExSE group [0,6 (−0,9–22,7) vs 1,1 (−1,1–15,7) ng/L, p=0,786]. Moderate correlation of hsTnT rise with DSE length was observed (r=0,43). Conclusions DSE leads to significant myocardial injury multiplied when atropine is used. No injury was observed in DIP and only mild was revealed in ExSE. This finding support ExSE as the preferred stress echocardiography method. Whether significant myocardial injury is causative of the higher adverse event rates in DSE remains to be determined. Funding Acknowledgement Type of funding sources: Public Institution(s). Main funding source(s): University Hospital Hradec Kralove, Czech RepublicFaculty of Medicine Hradec Kralove, Charles University, Czech Republic hsTnT change 0–180 min. the whole grouphsTnT change 0–180 min. w/wo atropine

Long term follow up of elderly patients treated with self-expanding transcatheter aortic valve implantation; a single center experience

Abstract Background and aims The information of long term clinical performance of transcatheter heart valves is limited. Our aim is to assess the clinical outcomes and rate of structural valve deterioration (SVD) in patients after self-expanding transcatheter aortic valve implantation (TAVI) at 10-year follow-up. Methods A total of 141 consecutive patients undergoing self-expanding TAVI for native aortic valve stenosis or failed aortic surgical bioprosthesis, between 2008 and 2012 at our institution were included. We considered SVD as defined for the consensus statement from the European Association of Percutaneous Cardiovascular Interventions (European Society of Cardiology/European Association for Cardio-Thoracic Surgery). SVD cumulative incidence was calculated considering death in the absence of valve damage as a competitive risk. Results At the time of TAVI mean age was 78±5 years, male 44%. Percutaneous prosthesis implanted were self-expanding in 100% of patients (size: 26 mm in 72%, 29 mm in 28%). Mortality at 1, 5, and 10-year follow-up was 14%, 32%, and 72%, respectively. There was one death due to prosthetic valve endocarditis. Of the total cohort, 11 patients had severe SVD, with a cumulative incidence at 10 years of 8,21 (95% CI 4.09- 14.14%). The rate of SVD at 4, 6, 8, and 10 years was 0%, 1.41%, 2.83%, and 8.21%, respectively (Figure 1 and 2). Of the 11 patients with severe SVD, seven died, two patients had reintervention (both had redo TAVI), and the other two patients remain in close follow-up. In survivors at 10-year follow-up (n=41) the median of mean gradient was 8 mmHg (interquartile Rank 6–13 mmHg) and in 8.4% an prosthetic valve regurgitation ≥moderate was detected. Diabetes, chronic obstructive pulmonary disease, chronic kidney disease, previous stroke and high pulmonary systolic pressure were independent predictors of global mortality. SVD was not associated with any of studied variables (Age, arterial hypertension, obesity, chronic kidney disease, atrial fibrillation, previous aortic bioprosthesis, left ventricle function &amp;lt;50%, prosthetic valve regurgitation, valve size and ballon postdilatation) Conclusions A low rate of SVD at 10-year follow-up was observed in this serie of elderly patients with severe aortic stenosis treated with self-expanding TAVI. This study provides insights into the long-term performance of self-expanding TAVI. Funding Acknowledgement Type of funding sources: None. Cumulative incidence of SVD and deathSVD with confidence intervals

Correlation between Pulmonary Artery Hypertension Caused by Acyanotic CHD with Left to Right Shunt and Increased Level of Endothelin-1

Background: Pulmonary hypertension is defined as a resting mean pulmonary artery pressure (mPAP) of 25 mmHg or above. PAH is a frequent complication of congenital heart disease (CHD), particularly in patients with left-to-right (systemic-to-pulmonary) shunts. Objective: The present study aimed to investigate changes in the blood level of endothelin-1 (ET-1) in patients of PAH complicated by acyanotic CHD and to detect possible correlation with different hemodynamic parameters. Patient and methods: 48 children were recruited in Pediatric Cardiology Unit, Pediatrics Department in Zagazig University Hospitals after obtaining the required permissions and informed consent from the their caregivers. They were divided into Group (A), which included 24 children with acyanotic CHD with left to right shunt with PAH and Group B included 24 children with acyanotic CHD with left to right shunt but no PAH. All children were subjected to clinical and radiological examination, echocardiography and measurement of endothelin-1 level as well as correlation between the studied parameters were performed. Results: the present results showed that Group A was significantly associated with previous need of hospital admission and insignificantly associated with ICU need. Endothelin-1 was significantly negatively correlated with weight and oxygen saturation (SPO2) but significantly positively correlated with systolic blood pressure (SBP), heart rate (HR), respiratory rate (RR) and pulmonary blood pressure. Significant area under the curve (AUC) with cutoff value >1.55 with sensitivity 85.05 and specificity 91.1%. Conclusion: Pulmonary hypertension (PAH) complicated by CHD can be predicted by estimation of endothelin-1 (ET-1) as an indicator of endothelial injury.

Mortality in Systemic Sclerosis-Associated Interstitial Lung Disease in Brazil: A Real-Life, Long-Term Follow-up Observational Study.

The aim of this study was to identify risk factors associated with mortality in patients with systemic sclerosis (SSc), particularly those with interstitial lung disease (ILD), over a long-term follow-up in a large Brazilian SSc cohort. We conducted a medical records review study of 380 scleroderma patients from 1982 to 2019. Systemic sclerosis ILD was considered in those with evidence of ILD on chest high-resolution computed tomography (HRCT). Causes of death were determined. Among the 380 SSc patients, SSc-ILD on chest HRCT was observed in 227 patients (59.7%). Seventy-two patients (18.9%) died during a mean follow-up of 7.2 years since the SSc diagnosis; among them, 57 (79.2%) had SSc-ILD, compared with 15 (20.8%) without SSc-ILD (p < 0.001). Of the 72 deaths, 51.4% were considered related to SSc, and ILD was the leading cause of death. The overall survival rates at 5, 10, and 15 years were 87.9%, 81.5%, and 74.9%, respectively. Kaplan-Meier analysis showed a significantly worse prognosis among patients with SSc-ILD than among those without ILD (p < 0.001). Among patients with SSc-ILD, disease duration of less than 4 years (p < 0.001), forced vital capacity <80% at baseline (p = 0.017), and pulmonary systolic arterial pressure ≥40 mm Hg on echocardiography (p < 0.001) were significantly associated with mortality by multivariate analysis. In Brazilian SSc patients, the presence of ILD was associated with a worse prognosis. The higher mortality among SSc-ILD patients, especially those with a shorter disease duration and forced vital capacity <80%, highlights the need for early screening and closer monitoring before irreversible lung function deterioration occurs.

DYSPNEA IN AN ADULT WITH ATRIAL SEPTAL DEFECT AND SJÔGREN’S SYNDROME: WHO’S TO BLAME?

ASD and more frequently the ostium secundum type is a relatively common adult congenital heart disease. Sjogren’s syndrome on the other side is the second most frequent auto immune disease, Involving the lungs in 9–20% of patients. We report the case of a 69 years old woman, complaining of a long-standing dyspnea and was diagnosed with Sjogren’s syndrom. Her CT scan and pulmonary function tests were normal. That lead to investigate for pulmonary hypertension as a potential cause for her dyspnea. A TTE was performed and estimated her systolic pulmonary pressure at 30 mmhg, and showed an OS ASD with left to right shunt. Right heart catheterization calculated her mPaP at 20 mmhg. She is scheduled for percutaneous closure of her OS ASD. There are only few cases reporting an association between ASD and Sjogren’s syndrome in polyendocrine syndrome, and even fewer without polyendocrine syndrome. Farook and Al. discussed a case of a women presenting OS ASD with SS complicated with PAH, suggesting an association between the two pathologies by inflammatory process, and Inoue et Al. presented a case of a women with polyartritis rheumatoid and Sjogren’s syndrome complicated with PAH, inducing a right to left shunt through a patent foramen oval. In our case, the ostium secundum type ASD with left to right shunt with mild pulmonary hypertension is probably the reason for her dyspnea, as there was no interstitial lung disease with normal CT and PFT.Unfortunately, there is no sufficient data suggesting an eventual association between ASD and Sjogren’s syndrome without polyendocrine syndrome. The learning point is the importance of screening for congenital heart disease in adult with unexplained dyspnea.

Improvement in Metabolic Co-Morbidities after Implantation of CardioMEMS in Patients with Heart Failure with Preserved Ejection Fraction Phenotype.

Background: Heart failure with preserved ejection fraction (HFpEF) patients often have other comorbidities, including obesity, dyslipidemia, hypertension, and diabetes, comprising the metabolic syndrome. The impacts of hemodynamic monitoring via CardioMEMS on these co-morbidities remain unknown. Methods: A retrospective analysis of 29 patients with HFpEF (EF 45% or greater) and CardioMEMS was performed at a single center. Weight, body mass index (BMI), systolic blood pressures (SBP), high-density lipoprotein (HDL), triglycerides (TGL), hemoglobin A1C (HbA1c), and pulmonary artery diastolic pressures (PADP) were assessed at baseline and six months post-implant. Paired t-tests and the Wilcoxon signed-rank test were used, as appropriate, to test differences between time points. Results: These patients were 69% female, with a mean age of 73 years, and 62% had non-ischaemic cardiomyopathies (NICM). At the time of CardioMEMS implantation, average PADP was 20.1 mmHg ± 5.7, weight was 102.6 kg ± 22.7, BMI was 38.0 kg/m2 ± 8.3, SBP was 135 mmHg ± 19, HDL was 42.4 mg/dL ± 11.3, and median TGL was 130 mg/dL (100, 180). At six months we witnessed a decrease by 20.9% in PADP to 15.9 mmHg ± 5.8, (p < 0.001). In addition, the following was noted: weight decreased by 2.5% to 100.0 kg ± 23.2, (p = 0.006), BMI reduced by 2.6% to 37.0 ± 8.2, (p = 0.002), SBP decreased by 6.7% to 126 mmHg ± 16 (p < 0.001), HDL increased by 10.8% to 47 mg/dL ± 11.9 (p < 0.001), and TGL decreased by 15.4% to 110 mg/dL (105, 135) (p = 0.001). 62% of patients were diabetic with no significant improvements in HbA1C values at the 6-month follow-up. Conclusion: The utilization of CardioMEMS to optimize PADP results in an improvement in the comorbidities associated with the metabolic syndrome. Further studies are warranted to validate these findings and delineate clinical significance.

B-PO05-182 IS THERE A POINT IN EVALUATING RIGHT VENTRICULAR GLOBAL LONGITUDINAL STRAIN PRIOR TO CARDIAC RESYNCHRONIZATION THERAPY?

Cardiac resynchronization therapy (CRT) is a well proven treatment for heart failure patients with reduced ejection fraction (HFrEF). There is a strong need to find new factors that predict and/or influence the response to CRT. Most previous studies have focused mainly on the left ventricle (LV). The role of the right ventricle (RV) in CRT patients is uncertain. We sought to analyze the value of right ventricle global longitudinal strain (RVGLS) evaluation prior to CRT. Our study included patients with HFrEF undergoing CRT. RVGLS was measured using two-dimensional images acquired from the four-chamber view for offline analysis using the strain software (EchoPAC, General Electric Vingmed Ultrasound). RVGLS was calculated by the average of 6 segmental values of the lateral wall and interventricular septum. We used the absolute value of RVGLS, measured prior to CRT and twelve months after implantation. The study population consisted of fifty-four patients with a mean age 64.0 ± 13.8 years, 55% male gender, 29% ischemic etiology of HFrEF. A baseline lower RVLGS was associated with more adverse cardiovascular events (HF hospitalizations and death) during follow up (r=-0.46, p=0.007) and a higher NYHA class at baseline (r=-0.49, p =0.003). RVGLS value varied significantly among NYHA classes (F (54,2) = 5, p =0.01). A lower baseline RVGLS was associated with a lower LVEF (r=0.47, p =0.004) and a more dilated LV (r=-0.46, p =0.004). A low RVGLS was also correlated with higher estimated pulmonary systolic pressure (p<0.001). Baseline RVGLS was significantly lower in patients without echocardiographic response to CRT compared to responders (p<0.001). RVGLS proved to be a good predictor for response to CRT with a good ability to discriminate between responders and non-responders (AUC = 0.85, 95% CI, 0.70-1). We propose a cut off value for RVGLS = - 12 (sensibility 73%, specificity 80%). Evaluation of RVGLS provides valuable prognostic information in HF patients undergoing CRT. A lower baseline RVGLS predicts lack of response to CRT and was associated with more adverse cardiovascular events during follow up. Measurement of RVGLS may be useful in the evaluation of HFrEF patients prior to CRT, pending validation in larger studies.