Pulmonary Artery Systolic Pressure Research Articles

May right heart failure cause pulmonary congestion in pulmonary arterial hypertension?

Abstract Aims Recent studies have shown that lung ultrasound-assessed pulmonary congestion is worse in heart failure when pulmonary vascular resistance (PVR) is increased, suggesting a paradoxical relationship between right heart failure and increased lung water content. Accordingly, we wondered if lung ultrasound would reveal otherwise clinically silent pulmonary congestion in patients with pulmonary arterial hypertension (PAH). Methods and results All patients referred for suspicion of PAH in a tertiary center from January 2020 to December 2022 underwent a complete diagnostic work-up including echocardiography, lung ultrasound and right heart catheterization. Pulmonary congestion was identified by lung ultrasound B-lines using an 8-site scan. The study enrolled 102 patients with idiopathic PAH (mean age 53±13; 71% female). WHO functional classes I, II and III were found respectively in 2, 52 and 46% of them. The N-terminal-pro-brain natriuretic peptide (NT-proBNP) was 377 pg/mL [interquartile range, IQR 218, 906]. B-lines were identified in 77 out of 102 patients (75%), with a median of 3 [IQR: 1-5]. At univariable analysis B-lines were positively correlated to male sex, age, NT-proBNP, systolic PA pressure (sPAP), right atrial pressure (RAP), PVR, left ventricular end-diastolic volume and tricuspid annulus plane systolic excursion (TAPSE), and negatively to cardiac output and stroke volume. At multivariable analysis, RAP (p<0.001; Fig 1), TAPSE/sPAP (p=0.001), and NT-proBNP (p=0.04) were independent predictors of B-lines. Conclusion Lung ultrasound commonly discloses pulmonary congestion in PAH. This finding is related to right ventricle to pulmonary artery uncoupling, and may tentatively be explained by increased central venous pressure impeding lymphatic outflow.Figure 1

Prognostic value of follow-up hemodynamics after initial treatment in pulmonary arterial hypertension

Abstract Background Hemodynamic variables such as right atrial pressure (RAP), cardiac index (CI) and mixed venous oxygen saturation (SvO2) have consistently been associated with survival in pulmonary arterial hypertension (PAH). The prognostic importance of hemodynamics after treatment initiation seems to be superior to baseline evaluation and stroke volume index (SVI) emerged as an independent prognostic parameter. New PAH treatments are, however, able to improve exercise capacity without increasing CI or SVI. Purpose The aim of this work was to define the prognostic role of follow-up hemodynamic parameters in a population of patients with idiopathic, hereditary, drug-induced PAH (I/H/D-PAH) and PAH associated with connective tissue disease (CTD-PAH) and congenital heart disease (CHD-PAH). Methods Treatment naïve PAH patients were assessed at baseline and at 1st follow-up (3-4 months after starting PAH-specific therapy; 1st F-UP) with 6-minute walk distance (6MWD), World Health Organization functional class (WHO-FC) and right heart catheterization (RHC). Collected hemodynamic parameters were: RAP, systolic, diastolic and mean pulmonary artery pressure (s/d/mPAP), CI, SVI, SvO2, pulmonary vascular resistance (PVR), pulmonary arterial compliance (PAC), cardiac efficiency (CE), pulmonary arterial elastance (Ea), resistance–compliance product (RC), right ventricular (RV) power, and RV stroke work index (RVSWI). The primary outcome was all cause death. We used stepwise Cox regression to assess variables obtained at baseline and at 1st F-UP. Results 794 patients with PAH were enrolled (54% I/H/D, 28% CTD, 18% CHD). A primary outcome occurred in 54% of patients over a median follow-up duration of 5.8 (2.4–11) years. In a multivariable model considering only baseline variables, no hemodynamic variables independently predicted prognosis but RAP. At first follow-up RHC (n=706), WHO-FC, 6-minute walk distance, RAP, and Ea were independently associated with death, adjusted for age, gender, and etiology of PAH. Because hemodynamic variables were highly correlated, we compared multivariable Cox regression models adding only variables with a correlation coefficient <0.6. In these models, RAP, Ea, PAC, CE, PVR, SvO2, CI, and SVI at follow-up RHC were independent predictors of death (Table). Conclusions Ea and right atrial pressure were the hemodynamic variables independently associated with death at 1st F-UP RHC after initial PAH treatment. These findings suggest that beyond improving RV function, RV afterload reduction can be considered a further treatment target.Table

Exercise stress echocardiography detects patients with paroxysmal/persistent atrial fibrillation

Abstract Background Atrial fibrillation (AF) is the most prevalent atrial tachyarrhythmia, affecting an estimated 2-4% of adults worldwide. AF is a well-recognized and treatable risk factor for stroke, but it often remains asymptomatic or subclinical, leading to underdiagnosis. This study aimed to identify distinguishing signs during exercise stress echocardiography (ESE) among patients in sinus rhythm (SR), with and without history of paroxysmal/persistent AF (PAF). Methods An international prospective cohort comprising 1035 consecutive patients was initially considered from 12 cardiology institutions. These patients were referred for clinically-driven ESE as part of the Stress Echo 2020-2030 study network. All patients underwent comprehensive ESE with the ABCDE protocol, which included assessment of B-lines, left ventricle contractile reserve (LVCR), ECG-based heart rate reserve (HRR), LV ejection fraction (EF), LV end-diastolic volume, E/e’, pulmonary artery systolic pressure estimation, tricuspid annular plane sytolic excursion (TAPSE), left atrium volume index (LAVi) and left atrium reservoir phase strain (LASr) at rest and with exercise. Results After excluding 89 patients who were in AF during the ESE, 946 patients in SR were included as the main study cohort (101 with and 845 without a history of PAF). A scoring system was then constructed using all independent variables that differentiate the two groups (those with and without history of PAF). Presence of systemic hypertension, rest LAVI>31ml/m2, rest |LASr|< 21%, stress LAVI >29 ml/m2, stress |LASr| <24%, stress E/e’ >7, ∆TAPSE <4.5 mm, HRR<1.87, and LVCR<1.6 were identified as the discriminators between patients with and without PAF. The composite score, summing all 9 items (with a total score range from 0 to 9), yielded a score of >4 as the best balance between sensitivity (87%) and specificity (60%) in predicting those with PAF. The receiver operating characteristic curve analysis of the scoring model showed an AUC of 0.79 (p-value <0.0001), Figure. Conclusion ESE evaluation can be a valuable adjunct for identifying patients in SR with history of PAF. This multifaceted approach enhances the potential for more accurate detection and clinical management of individuals in SR at risk for AF, who could be considered for aggressive monitoring programs to prevent the development of new onset AF and subsequent increase in cardiovascular risk.

Surgical reduction of a high-flow dialysis fistula has long-term positive effects of the heart

Abstract Introduction Part of chronic haemodialysis patients develop a high-flow arteriovenous fistula (AVF). The volume overload caused by the presence of a high-flow AVF leads to increased cardiac output, dilation of cardiac chambers, increased pulmonary artery pressure or even to the development of high-output heart failure. Our previous data showed a positive effect of AVF flow-reducing surgery in 6 weeks follow-up. Purpose The purpose of this study was to analyse the long-term effect of AVF blood flow (Qa) reduction on cardiac structure and function. Methods We included patients with high-flow AVFs (defined as Qa over 1500 mL/min) indicated for blood flow reduction surgery for heart failure symptoms or pre-defined echocardiographic changes (left ventricular hypertrophy, severe secondary valvular regurgitations, or pulmonary hypertension). Echocardiography was performed one day before the surgery, the 6 weeks, 6 months, and 12 months thereafter. Qa was measured by ultrasound during the same visits. Results 27 patients were included, 20 men and 7 women, aged 57 ± 13 years. The procedure led to an immediate decrease in Qa. However, we observed failure of the procedure within 1 year in 8 (= 30%) patients defined by increased Qa back to pre-surgery values. Detailed results are displayed in Table 1. Estimated pulmonary arterial systolic pressure and left atrial volume remained significantly lower after 1 year despite the Qa rise. Effective cardiac output (= difference of cardiac output and Qa) rose immediately and remained increased during the follow-up period despite the increase in AVF blood flow. Conclusions We observed a long-time positive effect of AVF blood flow reduction surgery on the heart despite a significant Qa rise. The effective cardiac output remained increased despite the gradual increase of Qa, probably due to the adaptation of systemic arterioles.

Development and validation of a predicting model for risk of mortality in heart failure patients with mildly reduced ejection fraction post discharge

Abstract Background Prognostic prediction for heart failure with mildly reduced ejection fraction (HFmrEF) patients remains challenging. We aimed to create and validate a mortality risk prediction model for HFmrEF patients at 6-month, 1-year, and 3-year post discharge. Methods Clinical data of 1691 HFmrEF patients registered in the heart failure registry from 2015 to 2020 at the Heart Center of our hospital were analyzed. Patients were assigned into a training (1183 patients) and validation cohort (508 patients) at 7:3 ratio. Predictive variables for mortality at various period post discharge were identified by the Least Absolute Shrinkage and Selection Operator (LASSO) regression analysis. The predicting model was then established based on these variables. Model performance was evaluated with ROC curve and Decision Curve Analysis (DCA). Results Eight predictors were identified including age, NT-proBNP, hemoglobin levels, use of beta-blockers, ACEI/ARB, invasive ventilation, PCI procedures, and pulmonary artery systolic pressure values. The model achieved a C-index of 0.748 (training set) and 0.755 (validation set). Area Under the Curve (AUC) for training set at 6 months, 1 year, and 3 years were 0.813, 0.784, and 0.774, and AUC for validation set were 0.775, 0.744, and 0.770, respectively. The DCA analysis confirmed the favorable net benefit of the established nomogram model. Conclusion This predicting model might be used for post-discharge risk stratification and individual decision-making of post-discharge management in HFmrEF patients.

RV-PA uncoupling is a strong predictor of 3-year all-cause mortality in transthyretin amyloid cardiomyopathy

Abstract Background Right ventricle to pulmonary artery coupling (RV-PAc) describes the right ventricle's ability to adjust to an increased afterload which, in case of transthyretin amyloid cardiomyopathy (ATTR-CM), can result from increased left ventricular diastolic stiffness due to fibril deposition. While RV-PAc is a validated prognostic parameter in pulmonary arterial hypertension (PAH), its prognostic relevance in ATTR-CM remains unclear. This study sought to evaluate the prognostic implications of impaired RV-PAc on survival in ATTR-CM. Methods In this two-centre study, RV-PAc was investigated by the echocardiographic surrogate of ratio of tricuspid annular plane systolic excursion to estimated pulmonary arterial systolic pressure (TAPSE/PASP) in 418 ATTR-CM patients, all treated with TTR stabilizer. The primary outcome was all-cause mortality. Receiver operation curves and Youden’s J analysis were applied to identify an optimal cut-off value of RV-PAc ratio. Results Within a median time of 631 (IQR 361-983) days after diagnosis, 14.4% of patients died. RV-PAc ratio at first presentation emerged as a robust marker for risk stratification with a determined optimal cut-off of 0.382mm/mmHg (area under the curve (AUC) 0.746, 95% CI 0.68-0.82). Patients with RV-PAc ratio ≤0.382mm/mmHg (impaired RV-PAc, n=158) exhibited significantly lower survival (HR 4.07, 95% CI 2.26-7.33, p<0.001) within 3 years of follow up than those with RV-PAc ratio > 0.382mm/mmHg. In multivariate Cox regression analysis, incorporating a range of known prognostic variables, reduced RV-PAc was a strong echocardiographic predictor of mortality (Hazard Ratio (HR) 2.99, 95% Confidence Interval (CI) 1.63-5.51, p <0.001). Conclusion Impaired adaption of the RV to increased afterload is associated with worse outcome in ATTR-CM patients. RV-PAc ratio can serve as an echocardiographic predictor for all-cause mortality within three years after diagnosis. Therefore, determination of RV-PAc could improve risk stratification for ATTR-CM patients.Figure_1_Kaplan-Meier curves

Accuracy of right atrial pressure estimation by transthoracic echocardiography

Abstract Background/Introduction Transthoracic echocardiography provides an estimate of right atrial pressure (RAP) using the guideline-recommend method of measuring inferior vena cava (IVC) diameter and collapsibility. Despite being ubiquitously reported and necessary for the estimation pulmonary artery systolic pressure, the accuracy of this method for RAP estimation has not been rigorously validated. Purpose To evaluate the accuracy of the guideline-recommended method for the estimation of RAP by TTE. Methods A single center, retrospective chart review of patients who had a TTE and right heart catheterization (RHC) within 48 hours of each other from January 2018 to December 2020. Maximum and minimum IVC diameter were measured by trained study personnel. Accuracy was then stratified by the presence/absence of a history of two variables that could modify IVC diameter independent of RAP—syncope, which is associated with more dilated IVC in some studies and liver disease, which could result in compression (from parenchymal fibrosis surrounding the IVC) or dilation (from diversion of portal blood flow through the IVC among other mechanisms) of the IVC. Results The 117 patients who met inclusion criteria had a median age of 67 years old (interquartile range [IQR] 58 – 75) and median RAP of 13 mmHg (IQR 8 – 18) on RHC. The median time between TTE and RHC was 9.6 hours (IQR 3.8 – 24.5 hours) during which 24 (20.5%) patients received intravenous fluids (median 220 mL administered; IQR 145 – 320). Forty-three (35.9%) received diuretics between the studies with most patients receiving either 1 (26 patients, 61.9% of those who received diuretics) or 2 (13 patients, 31.0%) diuretic doses. In evaluating accuracy, only 26 patient’s (20.5%) RAP by RHC fell within estimated RAP range by TTE (Figure 1). After excluding the 60 patients who received fluids and/or diuretics between the TTE and RHC, the TTE estimate was still only accurate in 13 (22.8%) patients. When analyzing how each subcomponent of the TTE guidelines for RAP estimation correlated with RAP via RHC, maximum IVC diameter and percent collapsibility had Pearson’s correlation coefficients of 0.47 and 0.24 respectfully (Figure 2A and 2B). Past medical history was significant for syncope in 16 patients (13.7%) and liver disease in 8 patients (6.8%). Compared to those without each factor, the absolute accuracy of the TTE estimate was lower when stratified by a history of syncope (12.5% accurate vs 21.8%, p = 0.60) and liver disease (12.5% vs 21.2%, p = 0.90) though neither were statistically significant. Conclusion In this retrospective chart review, RAP estimation by TTE using the guideline-recommended method had limited accuracy. Prospective evaluation with minimal time between RHC and TTE is needed to validate the accuracy of the TTE guidelines.Accuracy of TTE for RAP estimationCorrelation between RAP & TTE Variables

Gender-related differences in the timing of intervention for aortic stenosis: focus on cardiac damage

Abstract Background and aim: There is an increasing awareness of gender-related differences in the management of cardiovascular diseases. Our aim was to assess whether cardiac damage prior to intervention for severe aortic stenosis (AS) differs according to gender. Methods Retrospective analysis of a prospective cohort of patients with AS who underwent surgical aortic valve replacement (SAVR) and transcatheter aortic valve replacement (TAVR) in a tertiary care center from 2017 to 2022. Echocardiographic parameters prior to surgery were collected, and patients were classified into categories of a cardiac damage staging system. (1) Several echocardiographic variables according to gender were evaluated. Results 869 patients were included, of which 350 underwent TAVR and 519 were treated with SAVR. Females represented 52.4% (n=272) of TAVR patients and 37.7% (n=132) of SAVR patients. In the echocardiogram performed before the intervention, both in the TAVR and the SAVR cohort, female patients had worse diastolic function (significantly higher values of E/e’), and greater involvement of pulmonary vasculature damage (significantly higher pulmonary artery systolic pressure and worse right ventricular-arterial coupling (Table-Figure 1). When applying an available cardiac damage staging system (1), we documented that women were treated at a statistically significant more advanced stage compared to men (Figure 2). Conclusions There are gender-related differences in the timing of aortic stenosis intervention, both with TAVR and SAVR. Women are operated on at a more advanced stage of cardiac damage, particularly regarding the parameters of diastolic function and right-side damage. These findings should be taken into account to improve intervention timing and outcomes, especially for women.Table-Figure 1Figure 2

Unravel novel therapeutic targets in heart failure and associated pulmonary hypertension

Abstract Background Heart Failure (HF) is a complex clinical syndrome with poor prognosis. Pulmonary hypertension (PH) often complicates HF but can hardly be addressed therapeutically. Sodium-glucose co-transporter 2 inhibitors (SGLT2i) improve cardiovascular outcomes in patients with HF. Whether SGLT2i positively impact on HF-associated PH is poorly understood. Omics offer great promise in the discovery of novel biomarkers and therapeutic targets for HF and PH. Aims We investigated novel markers associated with HF and PH, as well as how these biomarkers vary in response to HF-modyfing therapies, including SGLT2i. We also explored the impact of SGLT2i, compared with conventional anti-HF therapy, on HF-associated PH and right ventricular function. Methods Seventy-four patients with HF and reduced ejection fraction (HFrEF) with/without diabetes were divided into a gliflozin (G)-group receiving 10 mg/day empagliflozin or dapagliflozin, and a control (C)-group receiving conventional anti-HF therapy. Resting echocardiography, analyses on senescence markers [leucocyte telomere length (LTL), mitochondrial DNA copy number (mtDNAcn)], as well as measurement of two microRNAs (miRNA-21 and miRNA-92, recently implicated in response to treatment in HFpEF patients), were performed. Shotgun proteomic analyses were conducted on peripheral blood mononuclear cells. Results Compared to group C, group G had a significantly higher ejection fraction (EF, 42±13 vs 33±8, p=0.001), reduced left ventricular filling pressures (11±3 vs 15±5, p=0.001), reduced pulmonary artery systolic pressure (PAPs, 31±11 vs 46±15, p=0.001), better right ventricular-pulmonary artery coupling index (0.64±0.31 vs 0.44±0.22, p=0.002), increased LTL (Figure 1 A), higher mtDNAcn (Figure 1 B), reduced miRNA-21 levels (Figure 1 C) and no significant changes of miRNA-92 (Figure 1 D). Functional proteomic analysis showed that, compared with the C-group, the protein cargo from the G-group was able to trigger several biological pathways, showing a significant activation of T lymphocytes immune response (p-value=9.67x10-06, z-score=2.21) chemotaxis of monocytes (p-value=9.39x10-07, z-score=2.0), leukocytes (p-value=9.67x10-10, z-score=2.0)and phagocytes (p-value)=3.10x10-10, z-score=2.03) (Figure 2). Compared with the C-group, the G-group showed a downregulation of activin signaling pathway (z-score=-2.12), which is a novel therapeutic target in pulmonary arterial hypertension (PAH). Conclusions In HF patients, SGLT2i therapy is associated with improved left ventricular function and improved pulmonary hemodynamics. Activin is overactive in HF patients and its serum levels may be reduced by SGLT2i. SGLT2i may preserve LTL and mtDNA-cn as well as modulate the expression of specific miRNA implied in the regulation of endothelial function. SGLT2i may represent an additional therapeutic tool in patients with HF-associated PH, an area with no approved treatment options beyond traditional HF therapy.Figure 1:genomic analysesFigure 2:proteomic analyses

The effects of SGLT2 inhibitors on right ventricle functions in heart failure patients: update meta-analysis of the current literature

Abstract Background There is some discrepancy in the present studies concerning the effect of sodium-glucose cotransporter type 2 (SGLT2) inhibitors on right ventricular (RV) functions in heart failure (HF) patients. The current meta-analysis was focused on determining the impact of SGLT2 inhibitors on RV functions in such individuals. Methods Two independent investigators searched PubMed, Google Scholar, and the Cochrane Library for articles of interest. To analyze heterogeneity, Higgins' I2 as well as prediction intervals and Egger's test were utilized to assess heterogeneity. The Newcastle-Ottawa standard ratings approach was used to assess the quality of observational studies. The Robin-I risk of bias algorithm was used to assess the bias risks of randomized studies. Results This meta-analysis evaluated 8 studies in total. Over the follow-up time frame, patients who used SGLT-2 inhibitors had substantially lower systolic pulmonary artery pressure (sPAP) and higher TAPSE values (mean difference (MD) = 1.30 [0.78;1.82], p =0.002 and MD =-5.39 [-7.88; -2.89], p=0.003, respectively). There was no significant difference in RVS’ values between follow-up and baseline (MD=1.38 [-1.35;3.80], p=0.169). However, as compared to the baseline period, fractional area contraction (FAC) values were substantially larger at the end of the follow-up period (MD=5.40 [3.74;7.07], p=0.015). Conclusion To the best of our knowledge, this is the first meta-analysis assessing the impact of SGLT2 inhibitors on RV function in HF patients. Our findings suggest that SGLT2 inhibitors may improve RV performance in HF patients.

A decade of follow-up: atrial fibrillation, pulmonary pressure, and the progression of tricuspid regurgitation

Abstract Background While Atrial fibrillation is considered a risk factor for tricuspid regurgitation (TR), prospective long term data in the field is lacking. This analysis aimed to identify risk factors of TR progression during a decade of follow up among patients with and without AF. Methods Patients with full echocardiographic and clinical follow of at least 5 years were included. Individuals presenting with significant TR at baseline were excluded. Patients were divided into two groups based on baseline diagnosis of AF, followed by stratification according to systolic pulmonary artery pressure (sPAP). The primary outcome was the occurrence of new significant TR (≥ Moderate). Results Study population included 15,957 patients with a median age of 63 (IQR: 54-72) of whom 6,068 (38%) were women and 1,837 (11.5%) had baseline AF. During a median follow-up period of 11 years (8.5 – 13.5), 1,191 (7.5%) patients developed significant TR. Compared with sinus rhythm, patients with AF were 4 and 2 times more likely to develop significant TR during follow up in a univariate and multivariate models, respectively (95% CI 3.66 - 4.68 and 1.98 – 2.56, p < 0.001 for both). Older age, female sex, chronic kidney disease (CKD), left heart disease (LHD) and impaired right ventricular (RV) function, rate control and permanent AF were all risk factors for TR progression. The association of baseline AF with TR during follow up was sPAP – dependent, such that among patients with normal sPAP AF associated risk was high while among patients with high baseline sPAP AF-associated risk was significantly lower (HR 2.87 vs. 1.77; p for interaction < 0.001). Competing risk analysis with death as competing event yielded consisted results. Conclusions Baseline AF is a strong and independent risk factor for TR development. This association is more pronounced among patients with normal pulmonary arterial pressures, emphasizing the need for focused research on preventing TR development in this population.

Valve unit instead of intensive care unit admission after transcatheter edge-to-edge tricuspid valve repair

Abstract Background Standardization of periprocedural pathways reduces the length of hospital stay and thus healthcare costs and increases patient safety. Post-procedure admission to the intensive care unit (ICU) after transcatheter edge-to-edge tricuspid valve repair (T-TEER) has been the standard of care. Due to the COVID-19 pandemic related decline in high-care hospital beds, our center established primary admission to a dedicated general cardiologic care ward, the valve unit (VU). Aim To assess benefits and risks of admission to the VU instead of ICU after T-TEER. Methods This retrospective observational study included 270 consecutive patients who underwent T-TEER between March 2017 and June 2023 at our university hospital. Patients were admitted to the ICU post-procedure up to April 9th 2020 as standard (ICU-group, n = 53). Subsequent patients were planned for admission to a dedicated VU (VU-group, n = 217). We compared the groups and assessed length of hospital stay and in-hospital complications. In the VU-group, we examined unplanned transfer to the ICU (cross-over) and its predictors. Results Monitoring at the VU included continuous telemetric ECG-recording, oxygen saturation assessment, periodical blood pressure measurements and 24-hours physician presence. In contrast to the ICU, only non-invasive blood pressure measurements, less frequent laboratory controls and less intense fluid monitoring took place. The postinterventional hospital stay of patients with planned VU admission was significantly shorter compared to patients with planned ICU admission (median 4 (interquartile range (IQR) 3 - 5) vs. 4 (IQR 4 - 5) days, p = 0.030). Remarkably, overall complication rates were low and cardiogenic shock, infections, bleeding, vascular complications, delirium and acute kidney injury requiring dialysis were similar in both groups. 37 patients that were planned for VU had to cross over to unplanned ICU admission (17.1 %). Patients that had crossed over to unplanned ICU treatment had significantly higher risk for acute kidney injury (20.0 vs. 10.0%, p = 0.039) and in-hospital mortality (5.6 vs. 0%, p = 0.045). Higher systolic pulmonary artery pressure (sPAP) (OR 1.048, 95 %-CI 1.015 – 1.082, p = 0.003), NYHA functional class >= III (OR 9.176, 95 % CI 1.141 – 74.396, p = 0.037), and pre-interventional tricuspid regurgitation (TR) grade V (OR 2.941, 95 % CI 1.089 – 7.970, p = 0.033) were found to independently predict cross-over to unplanned ICU treatment. Conclusion Postinterventional admission to the VU instead of ICU after T-TEER shortens postprocedural hospital stay. A small proportion of had an unplanned transfer to ICU, which was accompanied by slightly higher complication rates. This cross-over affects patients with more advanced disease indicated by high pulmonary pressures, NYHA class and TR grade. Thus, admission to a valve unit is favorable for most patients after T-TEER, but those with advanced disease should be monitored more closely.

Clinical, echocardiographic and haemodynamic predictors of morbidity and mortality in pulmonary hypertension: a nation-wide registry

Abstract Background and aims In this retrospective analysis of a nation-wide registry on pulmonary arterial hypertension (PAH), group IV and V, we aimed to evaluate the clinical, echocardiographic,haemodynamic and neurohumoral predictors of morbidity and mortality. Methods This study included 903 patients enrolled from 24 cardiology centers participating in the RegiStry on clInical outcoMe and sUrvival in pulmonaRy hypertension Groups (SIMURG II). ESC/ERS 2022 risk scoring model was used for risk predictions at baseline assessment. Composite endpoint (CEP) definitions were adopted from the SERAPHIN and GRIPHON trials. Results Age was 51.27 + 21.37 years, and 72 % of patients were female. Incident cases were noted in 65.9 % of overall group. Idiopathic PAH (IPAH), PAH-associated with congenital heart diseases (CHD-PAH), PAH-associated with connective tissue diseases (CTD-PAH), porto-PAH, Group IV and V pulmonary hypertension (PH) were documented in 33 %, 33.5 %, 12 %, 1.6 %, 20 % and 1.7 % of overall patients, respectively. Background mono and dual targeted combinations, and sequential dual or triple combinations were noted in 17 %, 57 % and 26 % of patients, respectively. Baseline low-, intermediate- and high-risk were noted in 1.2 %, 14.1 %, and 84.7 %, respectively. Median follow-up time was 867 (412-1667) days. Overall rates of mortality and CEP were 26 % and 39%, respectively. Prevalent versus incident cases were associated signifinatly lower mortality and CEP rates (p=0.028 and p=0.024, respectively). Mortality and CEP rates were 31 % and 44 % in IPAH, 20 % and 39 % in CHD-PAH, 31 % and 43 % in CTD-PAH, and 25 % and 30 % in group IV patients, respectively. CHD-PAH compared with other groups was associated with a higher Kaplan-Meier (K-M) survival and CEP-free survival (p< 0.0001 and p=0.00023, respectively). Survival was associated with prevalent versus incident status, baseline functional class (FC) and six-minute walk distance (6MWD) in all subgroups (p<0.0001 for all), NT-brain natriuretic peptide and right atrial area in IPAH,CHD-PAH and CTD-PAH, and mixed venous O2 saturation % in IPAH and CHD-PAH (p varying from <0.0001 to 0.027). But, TAPSE / systolic pulmonary artery pressure ratio, right atrial-pulmonary capillary wedge pressure difference, pulmonary vascular resistance and its ratio to systemic vascular resistance, cardiac index were not related with survival. Baseline high versus intermediate /low risk was associated with a lower overall survival and CEP-free survival ( p=0.03 and p=0.003, respectively). Male sex [hazard ratio(HR):1.73;1.2-2,51,p = 0.004], 6MWD (p<0.001), FC III/IV (HR: 2.52;1.47-4.32, p<0.001) and baseline low-risk (HR:0.37;0.21-0.65, p<0.001) were independent predictors of mortality. Conclusions Our nation-wide data revealed current insights regarding the clinical, echocardiographic,haemodynamic and neurohumoral predictors of morbidity and mortality in PAH and group IV PH.

Does the presence of severe pulmonary hypertension affect survival at 5 years follow-up in patients who underwent TAVI for severe aortic stenosis?

Abstract Background Pulmonary hypertension (PH) is common in patients with severe aortic stenosis (AS) and is associated with increased mortality after transcatheter aortic valve implantation (TAVI) as well as surgical aortic valve replacement (SAVR). Preprocedural systolic pulmonary artery pressure (sPAP) often improves after TAVI because the most common type of PH is postcapillary PH secondary to left-sided heart disease, which potentially improves after treatment for AS. However, there are limited data regarding the prognostic impact on outcomes after TAVI and their predictors. Purpose The aim of this study is to compare survival at 5 years between patients with severe PH against those who did not have severe PH who underwent TAVI. Methods Between January 2012 until December 2022, we carried out a retrospective study of all patients who underwent TAVI at our hospital. Severe PH was defined as the presence of sPAP >40mmHg on echocardiography. Patients with aortic regurgitation and mixed aortic valve disease were excluded. Co-morbid pulmonary disease was defined as the presence of any significant pulmonary disease including COPD and Asthma. Co-morbid neurological disease was defined as the presence of any significant neurological disease including CVA/ TIA. Diabetes mellitus was defined as per WHO and included patients who were diet, medication and insulin controlled. Survival status and date of death were ascertained from our electronic health records. Counts and incidence rates of clinical outcomes at 5-year follow-up were computed from Kaplan-Meier analysis (See Figure 1). A Cox proportional hazards model was used to compute HRs and 95% CIs for the study outcomes. Results Of the 274 patients available for analysis, 115 (14%) patients had severe PH. The mean age was 84 years in both cohorts whilst patients in the severe PH cohort were frailer by Katz Index Score. Death occurred in 67 patients out of 115 patients who had severe PH and in 87 out of 158 patients who did not have severe PH after a median follow-up time of 4.1 years (58% vs 55%; adjusted HR: 1.04; 95% CI: 0.71-1.51; P = 0.86). Conclusion Our data shows that presence of severe pulmonary hypertension in severe aortic disease patients who had undergone TAVI did not affect survival at 5 years follow up compared to patients without severe pulmonary hypertension undergoing TAVI. Determining predictors of mortality in this high-risk cohort is likely to be complex and multifactorial, owing to the severe multi-comorbidity precluding them from SAVR.

Real-world evidence on pulmonary arterial hypertension: interim analysis from the Italian observational study INSPECTIO

Abstract Background Pulmonary arterial hypertension (PAH) is a rare, progressive disease leading to right-sided heart failure. The interest in risk assessment based on non-invasive parameters is growing, and insights from clinical practice are needed in this regard. INSPECTIO is an Italian observational study aimed at filling this knowledge gap. The results of an interim analysis at month 12 are presented below. Purpose The primary objective was to assess the change from baseline to month 12 in the number of the non-invasive low-risk parameters among World Health Organization functional class, 6-minutes walking distance, Brain Natriuretic Peptide (BNP) or N-terminal proBNP. Secondary objectives are the evaluation of echocardiographic and haemodynamic parameters, and the proportion of patients in which the therapy was optimized according to the guidelines. Methods Prospective, multicentre study on PAH patients at low/intermediate mortality risk treated with macitentan and/or selexipag as part of the oral combination therapy. Results Among 177 patients who were enrolled in 29 centres, 148 patients [median age 63.0 years (Q1/Q3: 53.5/73.0), 76.4% females] completed the 12-month follow up and were considered for this analysis. The median time from PAH diagnosis was 22.6 months (4.9/60.1). Sixty-four (43.2%) patients had idiopathic PAH; 4 (2.7%) heritable; 80 (54.1%) associated with other diseases [58 (72.5%) connective tissue disease, 11 (13.8%) congenital heart disease corrected for at least one year, 5 (6.3%) portal hypertension, 5 (6.3%) human immunodeficiency virus infection, 1 (1.3%) drug and toxins]. At baseline, 45.9% patients and 28.4% were in double and triple oral combination therapy, respectively. Primary objective: at month 12, the number of noninvasive low-risk parameters increased in 43 (29.1%) patients and remained stable in 80 (54.1%) patients [mean change 0.16 (p=0.017)]. The values at baseline, at month 12 and the change from baseline for each noninvasive parameter are shown in Table 1. Mean right atrial (RA) area (end-systole) and tricuspid annular plane systolic excursion (TAPSE) remained unchanged while a reduction of systolic pulmonary artery pressure (sPAP) was observed. Regarding the haemodynamic parameters, the mean pulmonary arterial pressure decreased [median change -4.5, (p=0.0346)], while cardiac index, pulmonary vascular resistance, and RA pressure remained stable (Table 2). The number of patients on triple therapy increased from 42 to 51 (+21.4%). Conclusions This study confirms that a noninvasive low-risk profile can be achieved with current combination PAH therapy. The modest or absent changes in echocardiographic and hemodynamic parameters suggest that treatment of PAH in real world is yet to be improved; on the other hand, the optimization of therapy in a significant portion of patients can possibly account for the improvement or stabilization observed.Noninvasive parametersEcho and hemodynamic parameters

Right ventricular to pulmonary artery coupling credicts poor outcomes after interatrial shunting in heart failure

Abstract Background Left atrial decompression is under investigation for heart failure (HF) with the potential to improve symptoms and potentially clinical outcomes. However, heterogeneous outcomes have been observed in randomized controlled studies. Purpose This study aimed to explore whether right ventricular (RV) -pulmonary artery (PA) coupling, as assessed from the tricuspid annular plane systolic excursion (TAPSE) /systolic PA pressure ratio, can be useful in predicting outcomes after implantation of the interatrial shunting device. Methods A total of 106 HF patients, n=62 with reduced ejection fraction (HFrEF), n=44 with preserved ejection fraction (HFpEF), were prospectively enrolled in the PRELIEVE registry with the Atrial Flow Regulator (AFR) implantation. Serious adverse events included cardiovascular mortality and HF worsening (W). Results Serious adverse events (SAEs) occurred in a total of 19 (18%) patients. There were no differences in baseline comorbidities, KCCQ scores, the 6-minute walking distance between patients with and without SAEs (Table). Patients with SAEs showed higher systolic pulmonary arterial pressure, NT-proBNP, serum creatinine and lower TAPSE/PASP ratio. Incidence of SAEs was higher in patients within the first TAPSE/PASP vs the third tertile (59% vs 12%, p=0.026), respectively. A TAPSE/PASP of <0.55 was identified to bear the most optimal sensitivity to predict the event (AUC=0.683, CI95% (0.533-0.833). Conclusion The reduced TAPSE/PASP ratio was associated with higher rates of serious adverse events in patients with heart failure undergoing controlled inter-atrial shunting. The hypothesis generating finding that reduced RV-PA coupling may identify potential clinical non-responders to left atrial decompression should be further prospectively validated.

Pulmonary valve acceleration fraction as a novel echo parameter to evaluate systolic pulmonary artery pressure during exercise echocardiography

Abstract Background/Introduction Long-COVID is a disabling chronic condition. Some patients have features of exercise-induced pulmonary hypertension (PHT) but non-invasive assessment during exercise stress echo (SE) is often limited by absence of reliable jet of tricuspid regurgitation (TR). We aimed to investigate novel Doppler echo parameters elicited from right ventricular (RV) outflow tract to aid diagnosis of exercise induced PHT among patients referred to our centre with Long-COVID symptoms. Purpose We investigated the ratio of the pulmonary valve acceleration time (PV AccT) to RV ejection time (RV ET) to calculate the pulmonary acceleration fraction (PV AccT/RV ET), thereby adjusting to heart rate. To identify its utility to estimate pulmonary artery pressure (PASP) during SE we correlated the PV AccT/RV ET and the TR-estimated RV systolic pressure (RVSP) in patients referred for evaluation of exercise-induced PHT in Long-Covid patients. Methods We developed a dedicated Covid-19 SE protocol to assess RV and pulmonary hemodynamics. From November 2022 to February 2023 all consecutive patients with Long-COVID symptoms underwent supine bike exercise with 3-min increments of workload of 25W. We did not evaluate the inferior vena cava during exercise, therefore estimated pressures from maximal TR jet velocities only. Results We enrolled 93 consecutive patients. The mean age was 50.1 years, 42.9% were female. No patients had RV impairment or RVSP >40mmHg at baseline. The average exercise time was 12.4 minutes, only 33% achieved the sub-maximum target heart rate (THR), in 50/93 (53.7%) reasons for termination were recorded as shortness of breath. The pulmonary acceleration fraction could be recorded in every patient at rest and at stress, while 20/92 (21.7%) patients had insufficient spectral Doppler profile of TR to estimate RVSP. The PV acceleration fraction was correlated with the available RVSPs during exercise (Spearman’s ϱ -0.446 (95% CI -0.606- -0.251[p<0.0001]). ROC analysis indicated a pulmonary acceleration fraction ≤0.44 was associated with the maximum Youden index to discriminate an increase in RVSP >20mmHg during exercise (AUC =0.731 [p<0.001]) with a sensitivity and specificity of 70.0% and 80.0%. In logistic regression analysis, a PV acceleration fraction ≤0.44 was independently associated with an increase in RVSP>20mmHg during exercise independently of age, gender and baseline LVEF, LVEDV, TAPSE and baseline RVSP (p<0.001). Conclusions Significant proportion of Long-COVID patients are limited by symptoms and not able to achieve THR during exercise. PV Acc T/ PV ET correlates well to RVSP and can be used to estimate PA pressure. A threshold of 0.44 appears independently associated with a benchmark of PA systolic pressure increase of >20mmHg. Further studies needed to evaluate this new marker of pulmonary hypertension in other group of patients.

Pulmonary hypertension in patients on chronic hemodialysis

Abstract Introduction Pulmonary hypertension (PH) is a common condition in patients with advanced chronic kidney disease and is associated with higher morbidity and mortality. High arteriovenous fistula (AVF) flow is one of known etiological factors, but the association of AVF flow within the acceptable range and PH has not been tested. Moreover, the prevalence of PH differed among various studies. Purpose The aims of this study were: 1. to describe the prevalence of PH in the Czech hemodialysis population; 2. to analyze the relation between dialysis fistula flow and PH; 3. to reveal other etiology of PH in a cross-sectional non-invasive trial. Methods We analyzed index visits of the cohort CZecking HF-CKD study (ISRCTN 18275480). Thus, this is a cross-sectional analysis based on detailed echocardiography with cardiac output (CO) calculation, evaluation of the central venous pressure (CVP) and AVF flow, bio-impedance and basic laboratory tests. All these measurements were done within an hour. The presence of PH was based on the peak systolic pulmonary arterial pressure (PASP) estimation above 35 mmHg. Results We analyzed data of 162 patients. They were 73,2 ± 12,6 years old, dialysis vintage 30 ± 69 months. Pulmonary hypertension was present in 35 % of analyzed patients. Among these patients, mild PH was present in 35 %, moderate in 53 % and severe in 12 %. There was no significant impact of AVF/AVG flow on the presence of PH or PASP value (Table 1.). However patients with PH had higher prevalence of heart failure (HF), which was present in 86 % of patients with PH and only in 46 % without PH (p<0.00001), see Figure 1. This and other differences presented in Table 1. document significant contribution of postcapillary PH. Patients with PH were also more overhydrated when considered by CVP, by overhydration measurement using bioelectrical impedance analysis and had higher N-terminal pro brain natriuretic peptide (NTproBNP) (Table 1.). There was a positive correlation between systemic vascular resistance (SVR) and PASP (R=0,333, p= .001). Conclusions PH is present in approximately one third of the dialysis patients. The presence of heart failure and changes of left heart chambers show for the postcapillary etiology of PH. Neither the prevalence nor the severity of PH were significantly related to arteriovenous access flow.

Adverse prognostic implications of increased left ventricular force in hypertrophic cardiomyopathy

Abstract Background The left ventricular (LV) force, also known as elastance, serves as a load-independent indicator of contractility and can be noninvasively assessed through echocardiography. In hypertrophic cardiomyopathy (HCM), the heightened presence of the active state of myosin heads results in an increased LV force. Purpose To assess the prognostic value of increased LV elastance at rest in patients with HCM. Methods We enrolled 1420 HCM patients (age 50±16 years, 907 males, 64%) with ejection fraction (EF) ≥50%, referred for rest transthoracic echocardiography (TTE) in 10 quality-controlled labs from 7 countries. TTE assessment included peak left ventricular outflow tract gradient (LVOTG), EF, and LV force (systolic blood pressure + LVOTG/LV end-systolic volume assessed with 2-D, mmHg/mL). All patients were followed up. All-cause death was the outcome measure. Results At a median follow-up of 83 months, 150 deaths occurred (Group 1). At study entry, Group 1 patients had the same ESC-Sudden cardiac death score compared to survivors (Group 2). In Group 1 compared to Group 2, TTE showed higher values of MR severity, E/e’ , left atrial volume index, estimated systolic pulmonary artery pressure, and force (see table). At multivariable Cox analysis, only age (HR =1.08, 95% CI=1.03-1.14, p=0.001) and force > median value of 5.3 mmHg/mL (HR = 2.14, 95% CI 1.53-2.99, p=0.020) were independent predictors of mortality. Ten-year survival was 95% in the pooled first (<3.8 mmHg/mL) and second (3.8-5.2 mmHg/mL) quartiles vs 80% in the pooled third (5.3-7.8 mmHg/mL) and fourth quartiles (>7.8 mmHg/mL), see figure. Conclusion HCM patients with higher values of resting LV elastance show a worse survival, highlighting the dark prognostic side of an excess of force in these patients. Table Legends E/e’, early mitral inflow to early mitral annulus motion ratio, EF, left ventricular ejection fraction, LAVI, left atrial volume index; LVOTG, left ventricular outflow tract peak gradient, MR, mitral regurgitation; MWT, maximal wall thickness, NYHA, New York Heart Association classification, RWT, relative wall thickness; SCD risk, risk score for sudden cardiac death in hypertrophic cardiomyopathy, SPAP, systolic pulmonary arterial pressure.Table.Clinical and TTE findingsFigure.Survival in the force quartiles

TAPSE/sPAP by echocardiography to detect elevated pulmonary vascular resistance> 4 WU in postcapillary pulmonary hypertension patients: insights from the French PH HF registry

Abstract Background Post-capillary pulmonary hypertension (pcPH) lacks effective treatment options. Patients with a PVR > 4 WU, known as combined pcPH (cpcPH), may benefit from investigational drugs like sotatercept. Identifying cpcPH patients suitable for vasodilation therapy in echocardiography labs is critical. Purpose To pinpoint an echocardiographic parameter capable of detecting cpcPH patients with a PVR above 4WU, addressing a common challenge in clinical practice. Methods In this study, 225 participants from the French PH-HF registry, all diagnosed with heart failure and a preserved ejection fraction, were examined. These patients underwent right heart catheterization and got ultrasound examinations within a 24-hour timeframe. The pulmonary vascular resistance were calculated using previously established methods, and data from standard echocardiography, including assessments of diastolic function, were gathered. Results 69 patients exhibited a pulmonary vascular resistance (PVR) greater than 4 WU, while 156 patients had a PVR ≤ 4 WU. Age averaged 69±12 years. Mean pulmonary artery pressure, wedge pressure, cardiac output, and pulmonary vascular resistance were 39±9 mm Hg, 22±4 mm Hg, 5.1±1.7 l/min, and 3.5±2.0 WU, respectively. Comparative analysis between patients with PVR ≤ 4 WU and those with PVR > 4 WU revealed similar ejection fraction (EF), left atrial volume index, and E/A ratio by echocardiography (p=0.97, p=0.69, p=0.43, respectively). However, patients with PVR > 4 WU showed elevated E/e’ (p=0.008), higher systolic pulmonary artery pressure (sPAP, p=0.001), but reduced myocardial S and e’ tissue Doppler velocities (p=0.001) and tricuspid annular plane systolic excursion (TAPSE) (p=10^-5). Notably, the relationship between TAPSE/sPAP and PVR > 4 was curvilinear and strong (p=0.001, FIG 1). Using ROC curve analysis, patients with TAPSE/sPAP < 0.38 mm/mmHg were identified to have PVR > 4 WU with a sensitivity and specificity of 68%. Conclusion Within the scope of postcapillary pulmonary hypertension, right ventricular arterial coupling is a simple ultrasound parameter potentially effective in identifying individuals exhbiting PVR > 4 WU with a good sensitivityFigure 1:PRV and coupling plotFigure 2:RV coupling ROC