Higher sPAP Research Articles

Elevated systolic pulmonary artery pressure is a substantial predictor of increased mortality after transcatheter aortic valve replacement in males, not in females

BackgroundWhile pulmonary hypertension (PH) in patients with severe aortic valve stenosis (AS) is associated with increased mortality after transcatheter aortic valve replacement (TAVR), there is limited data on gender differences in the effects on long-term survival.ObjectiveThe aim of this retrospective, multicenter study was to investigate the prognostic impact of pre-interventional PH on survival of TAVR patients with respect to gender.Methods303 patients undergoing TAVR underwent echocardiography to detect PH prior to TAVR via measurement of systolic pulmonary artery pressure (sPAP). Different cut-off values were set for the presence of PH. The primary endpoint was all-cause mortality at 1, 3 and 5 years.ResultsKaplan–Meier analysis by gender showed that only males exhibited significant increased mortality at elevated sPAP values during the entire follow-up period of 5 years (sPAP ≥ 40 mmHg: p ≤ 0.001 and sPAP ≥ 50 mmHg: p ≤ 0.001 in 1- to 5-year survival), whereas high sPAP values had no effect on survival in females. In Cox regression analysis based on the selected sPAP thresholds, male gender was an independent risk factor for long-term mortality after TAVR in all time courses.ConclusionMale gender was an isolated risk factor for premature death after TAVR in patients with echocardiographic evidence of PH and severe AS. This could mean that, the indication for TAVR should be discussed more critically in men with severe AS and an elevated sPAP, while in females, PH should not be an exclusion criterion for TAVR.Graphical abstractGraphical abstract of the study (Created with BioRender.com)Image material of CoreValve™ Evolut™ was kindly provided by © Medtronic Inc.

346 IMPACT OF EXERCISE-INDUCED PULMONARY HYPERTENSION ON THE RIGHT VENTRICLE AND WORSENING OF CARDIOVASCULAR RISK IN HIV PATIENTS

Abstract Background and Aim Exercise-induced pulmonary hypertension (ExPH), due to impaired pulmonary vascular and right ventricular contractile reserve on effort,predicts clinical outcomes, such as all-cause mortality or cardiovascular (CV) hospitalizations in patients with dyspnea on effort. We investigated its prognostic significance in HIV patients at risk for Pulmonary Arterial Hypertension (PAH). Methods In 52 consecutive HIV patients with either low (n=47) or intermediate probability (n=5) of PH at rest, we evaluated at time 0 and after 2 years the prognostic determinants of CV risk: onset or progression of heart failure/syncope; worsening of functional class; functional performance at the 6-Minute Walking Test and at cardiopulmonary exercise test (CPET); right atrial area; and pericardial effusion. We assigned a severity score 1-3 to each prognostic determinant, derived an overall CV risk score, and its 0-2 years change. Patients were classified as either at low, intermediate or high probability of ExPH at Stress Echocardiography (ESE), while ExPH at CPET was defined as absence of PH at rest, reduced peak VO2, VE/VCO2 >30 at anaerobic threshold, reduced O2 pulse, and ΔVO2/ΔW <9 mL/min/W. We then correlated ExPH at time 0 with clinical worsening (risk score increase >20% after 2 years). Results Right ventricle (RV) systolic function was significantly reduced in patients with ExPH compared to those without ExPH at CPET, as well as in patients with intermediate/high compared to those with low probability of ExPH at ESE, who exhibited worse values of TAPSE and FAC (p<0.001 and p=0.01, respectively). A significant higher proportion of patients with ExPH (CPET) or with intermediate/high probability of ExPH (ESE) had higher sPAP (p<0.001), mPAP (p=0.004), higher TRV (p=0.006) as well as higher right atrial area (p<0.001) and indexed right atrial volume (p=0.004). Total pulmonary vascular resistance (expressed by the ratio between TRV and velocity-time integral at the level of right ventricular outflow tract) was higher in patients with ExPH as well as in patients with intermediate/high probability of ExPH (p<0.001). Patients with intermediate/high probability of ExPH at ESE showed a trend towards clinical worsening compared to those with low probability of ExPH, albeit not statistically significant (p=0.137). In patients with low probability of ExPH, none had >20% increased CV risk score after 2 years. We found an association between higher NT-proBNP and the presence or intermediate/high probability of ExPH after 2 years (p=0.048 at CPET, p=0.033 at ESE). Conclusions At short follow-up, ExPH is associated with a worsening trend in the CV risk score which, if confirmed after longer follow-up, could contribute to better risk stratification in HIV patients.

Impact of Exercise-Induced Pulmonary Hypertension on Right Ventricular Function and on Worsening of Cardiovascular Risk in HIV Patients.

Exercise-induced pulmonary hypertension (ExPH) predicts clinical outcomes, such as all-cause mortality and cardiovascular (CV) hospitalizations, in patients with dyspnea on effort. We investigated its prognostic significance in human immunodeficiency virus (HIV)-affected patients. In 52 consecutive HIV patients with either low (n = 47) or intermediate probability (n = 5) of PH at rest, we evaluated-at time 0 and after 2 years-the prognostic determinants of CV risk, according to the 2015 European Society of Cardiology (ESC)/European Respiratory Society (ERS) Guidelines. Patients were classified with or without ExPH at stress echocardiography (ESE) and cardiopulmonary exercise test (CPET). We then related ExPH at time 0 with clinical worsening (CV risk score increase >20% after 2 years). Right ventricle (RV) systolic function was significantly reduced in patients with ExPH compared to those without ExPH at CPET. This also occurred in patients with intermediate/high probability compared to those with low probability of ExPH at ESE. The former exhibited worse values of TAPSE and FAC (p < 0.001 and p = 0.01, respectively). A significantly higher proportion of patients with ExPH (CPET) or with intermediate/high probability of ExPH (ESE) had higher sPAP (p < 0.001), mPAP (p = 0.004) and higher TRV (p = 0.006), as well as higher right atrial area (p < 0.001) and indexed right atrial volume (p = 0.004). Total pulmonary vascular resistance (expressed by the ratio between TRV and the velocity-time integral at the level of the right ventricular outflow tract) was higher both in patients with ExPH and in those with intermediate/high probability of ExPH (p < 0.001). Patients with intermediate/high probability of ExPH at ESE showed a trend (p = 0.137) towards clinical worsening compared to those with low probability of ExPH. No patients with low probability of ExPH had a >20% increased CV risk score after 2 years. We found an association between higher NT-proBNP and the presence or intermediate/high probability of ExPH after 2 years (p = 0.048 at CPET, p = 0.033 at ESE). The assessment of ExPH may predict a trend of increasing CV risk score over time. If confirmed at a longer follow-up, ExPH could contribute to better risk stratification in HIV patients.

Coronavirus disease 2019 and cardiovascular disease: what we have learnt during the last 2 years.

Coronavirus disease 2019 and cardiovascular disease: what we have learnt during the last 2 years.

Right ventricular strain related to pulmonary artery pressure predicts clinical outcome in patients with pulmonary arterial hypertension.

In pulmonary arterial hypertension (PAH), the right ventricle (RV) is exposed to an increased afterload. In response, RV mechanics are altered. Markers which would relate RV function and afterload could therefore aid to understand this complex response system and could be of prognostic value. The aim of our study was to (i) assess the RV-arterial coupling using ratio between RV strain and systolic pulmonary artery pressure (sPAP), in patients with PAH, and (ii) investigate the prognostic value of this new parameter over other echocardiographic parameters. Echocardiograms of 65 pre-capillary PAH patients (45 females, age 61 ± 15 years) were retrospectively analysed. Fractional area change (FAC), sPAP, tricuspid annular plane systolic excursion, and RV free-wall (FW) longitudinal strain (LS) were measured. A primary endpoint of death or heart/lung transplantation described clinical endpoint. Patients who reached a clinical endpoint had worse functional capacity (New York Heart Association), reduced RV function, and higher sPAP. Left ventricle function was similar in both groups. Only RVFW LS/sPAP ratio was found as an independent predictor of clinical endpoint in multivariable analysis (hazard ratio 8.3, 95% confidence interval 3.2-21.6, P < 0.001). The RWFW LS/sPAP (cut-off 0.19) demonstrated a good accuracy for the prediction of reaching the clinical endpoint, with a sensitivity of 92% and specificity of 82.5%. RVFW LS/sPAP ratio significantly predicts all-cause mortality and heart-lung transplantation, and was superior to other well-established parameters, in patients with pre-capillary PAH. We therefore propose RVFW LS/sPAP as a new prognostic echocardiographic marker.

The MIDA quantitative international registry: prognostic implications of moderately elevated pulmonary artery pressure

Abstract Funding Acknowledgements Type of funding sources: None. Background Pulmonary hypertension is a frequent complication of severe degenerative mitral regurgitation (DMR) associated with major outcome implications. However, whether pulmonary hypertension is linked with worse outcome in less that severe MR is uncertain and even more unsubstantiated is the link of elevated systolic pulmonary artery pressure (sPAP) &amp;lt; 50mmHg with clinical presentation and outcome. Purpose To assess the outcome implication of sPAP elevation, even moderate, among mitral regurgitation severity subgroups. Methods The MIDA-Quantitative (MIDA-Q) unprecedented registries included 7373 consecutive patients (age 64 ± 17 years, 45% women, follow-up 5.5 ± 3.4 years) with isolated DMR diagnosed at tertiary (European/North-American/Middle East) centers in which systolic pulmonary artery pressure (sPAP) was measured prospectively at baseline. Long-term survival overall, under medical management and post-mitral surgery was analyzed. Results Elevated pulmonary pressure (sPAP &amp;gt;50mmHg) was observed in 1371 patients (19%, mean 63 ± 13mmHg) and moderate increase in pulmonary pressure (35&amp;lt; sPAP &amp;lt; 50mmHg) in 1874 patients (25%, mean 41 ± 14mmHg), with no/mild MR in 4067 (50%), moderate in 2073 (25%), and severe or above in 2047 (25%), mean ERO 0.24 ± 24cm2, RVol 37 ± 35mL and posterior leaflet prolapse in 34%. sPAP severe but also moderate both strongly and independently linked to more severe clinical presentation, with more dyspnea, more AFib, and impaired renal function (P ≤ 0.0001). &amp;lt;SPAP&amp;lt; &amp;gt;By sPAP categories, 35 &amp;lt; sPAP&amp;lt; 50mmHg (vs. 35mmHg) was independently associated with worse outcome under medical management adjusted-HR 1.62[1.40-1/87], with considerable excess-mortality for sPAP &amp;gt; 50mmHg (vs. &amp;lt;35mmHg) adjusted-HR 2.54[2.17-2.96], all P &amp;lt; 0.0001. As continuous variable, sPAP was associated with worse outcome adjusted-HR 1.25[1.21-1.29], P &amp;lt; 0.0001 per 10mmHg-increase. Mitral valve surgery (performed in 2378 patients, 32%) improved outcome without alleviating completely higher mortality associated with sPAP &amp;gt; 50mmHg (P &amp;lt; 0.0001). Conclusion In this very large international cohort of patients with DMR of all range and prospective sPAP grading, higher sPAP is associated at diagnosis with more severe clinical presentation. Long term, sPAP &amp;gt; 50mmHg but also 35-50mmHg is independently of all confounders, associated with worse mortality. Thus careful assessment and consideration for mitral surgery/transcatheter therapy is warranted even in patients with sPAP &amp;lt;50mmHg.&amp;lt;/SPAP&amp;lt; &amp;gt; Abstract Figure. Survival stratified by sPAP Categories Abstract Figure. Postop survival by sPAP Categories

Left atrial function is impaired in cardiac amyloidosis and other cardiomyopathies with hypertrophic phenotype: haemodynamic correlations, pathophysiological consequences and prognostic implications

Abstract Background Left atrial function (LAF) is emerging as a novel determinant of clinical status and outcome in cardiomyopathies. However, few studies compare LAF between CA subgroups and between CA and other hypertrophic cardiomyopathies. Purpose This study explores the LAF in cardiomyopathies with hypertrophic phenotype and between CA subgroups and its consequences on clinical status, haemodynamic consequences and survival. Methods We enrolled 50 patients with CA (26 with AL and 24 with wild type ATTR form), 75 patients with LV hypertrophy (LVH) [25 with hypertrophic cardiomyopathy (HCM), 25 with hypertensive cardiomyopathy (HypCM), and 25 with aortic stenosis (AS)]. Besides routine echocardiographic measurements, we analysed LAF using the phasic method (LAEI as reservoi, LAPEF as conduit, LAAEF as pump and TLAEF as total emptying LA function). Results The ATTR showed higher atrial dimensions with a significant reduction in the reservoir and total LA emptying function compared to the AL group (see Table 1). Instead, compared to the LVH group, CA patients showed higher atrial dimension with all LAF phasic parameters reduced, higher LV filling pressures and reduced biventricular function. Then, we further divided the CA and LVH group into subgroups based on the presence or absence of LA dysfunction (LADys+) defined as TLAEF values below the median [TLAEF &amp;lt;50,2%; range 9,3–70,9%]. Patients in CA/LADys+ group showed the worst NYHA class, higher sPAP and lower values of TAPSE and TAPSE/sPAP ratio (see Figure 2). After a follow-up of 24 months, 19 patients died from cardiovascular causes [0/8 in CA/LADys-, 15/42 in CA/LADys+, 0/60 in LVH/LADys- and 4/26 in LVH/LADys+ group; (log-rank χ2 29,6; p&amp;lt;0,0001)]. To predict whether LAF could predict cardiovascular deaths sequential multivariate model was employed, and TLAEF was entered together with established clinical and echocardiographic parameters (NYHA class, LAVI, E/Em, sPAP, TAPSE and TAPSE/sPAP ratio). At the final backward analysis, LAVI, TAPSE/sPAP and TLAEF were the independent prognosticators for adverse events. Discussion The LAF is significantly impaired in CA and associated with worst clinical status, higher incidence of RV dysfunction and higher LV filling and pulmonary pressure. Moreover, LADys is significant associated with higher cardiovascular mortality. LADys results from chronic pressure overload due to LA's exposition to the higher LV diastolic pressure due to impaired LV compliance, and from direct infiltration in CA The result is a progressive LA remodelling with an increased LA pressure and consequenT backward transmission to the pulmonary venous system and to RV. Conclusions The TLAEF is a novel parameter of LAF that correlates with increased pulmonary vascular resistance and RV dysfunction. It seems a promising novel prognosticator and amarker of the haemodynamic consequences of LADys. Funding Acknowledgement Type of funding sources: None. Table 1Figure 1

Easily available ECG and echocardiographic parameters for prediction of left atrial remodeling and atrial fibrillation recurrence after pulmonary vein isolation: A multicenter study.

The assessment of noninvasive markers of left atrial (LA) low-voltage substrate (LVS) enables the identification of atrial fibrillation (AF) patients at risk for arrhythmia recurrence after pulmonary vein isolation (PVI). In this prospective multicenter study, 292 consecutive AF patients (72% male, 62 ± 11 years, 65% persistent AF) underwent high-density LA voltage mapping in sinus rhythm. LA-LVS (<0.5 mV) was considered as significant at 2 cm2 or above.Preprocedural clinicalelectrocardiogramand echocardiographic data were assessed to identify predictors of LA-LVS. The role of the identified LA-LVS markers in predicting 1-year arrhythmia freedom after PVI was assessed in 245 patients. Significant LA-LVS was identified in 123 (42%) patients. The amplified sinus P-wave duration (APWD) best predicted LA-LVS, with a 148-ms value providing the best-balanced sensitivity (0.81) and specificity (0.88). An APWD over160 ms was associated with LA-LVS in 96% of patients, whereas an APWD under145 ms in 15%. Remaining gray zones improved their accuracy by introduction of systolic pulmonary artery pressure (sPAP)of 35 mmHg or above, age, and sex. According to COX regression, the risk of arrhythmia recurrence 12 months following PVI was twofold and threefold higher in patients with APWD145-160and over 160 ms, compared to APWD under145 ms. Integration of pulmonary hypertension further improved the outcome prediction in the intermediate APWD group: Patients with APWD 145-160 ms and normal sPAP had similar outcome than patients with APWD under145 ms (hazard ratio [HR] 1.62, p = .14), whereas high sPAP implied worse outcome (HR 2.56,p < .001). The APWD identifies LA-LVS and risk for arrhythmia recurrence after PVI. Our prediction model becomes optimized by means of integration of the pulmonary artery pressure.

Risk of atrial fibrillation in hypertrophic cardiomyopathy: a clustering analysis based on the French registry on hypertrophic cardiomyopathy (REMY)

Abstract Funding Acknowledgements Type of funding sources: Public hospital(s). Main funding source(s): CHU Rennes, Inserm, LTSI – UMR 1099, F-35000 Rennes, France Assistance Publique-Hôpitaux de Paris-Centre Université de Paris, University of Paris onbehalf REMY register Paroxysmal or chronic atrial fibrillation (AF) is frequent in hypertrophic cardiomyopathy (HCM),(20%-25% of patients), and is often considered as an important disease turning point. The aim of this study is to determine HCM-phenogroups with different risk of AF-occurrence at 5-year. We applied the Bayesian method to differentiate phenogroups of patients with different risks of AF across a French hospital registry of adult HCM(REMY). Data were prospectively recorded on 5 years follow-up. 1431 HCM patients were recruited, including 1275 analyzed. The population included 412 women. AF-occurred in 167 (11.6%) patients. 3 phenogroups were defined according to their common characteristics. Patients at the highest risk were more often female, with more frequent comorbidities, greatest anteroposterior LA diameter, diastolic dysfunction, outflow-tract obstruction or mitral valve abnormality, and presented higher sPAP or right ventricular dysfunction. These also had a higher risk of all-cause hospitalizations and death. Based on a clustering analysis, 3 phenogroups of HCM according to the risk of AF occurrence can be identified. It can indicate which patients should be more monitored. 3 different AF-risk groups Intermediate risk group n = 524 High-risk group n= 207 Low-risk group n = 544 P Gender = Males (%) 338 (64.5) 103 (49.8) 422 (77.6) &amp;lt;0.001 Age (median [IQR]) 59.00 [47.00, 66.00] 63.00 [54.00, 74.00] 50.00 [38.00, 60.00] &amp;lt;0.001 Stroke (%) 29 (5.5) 44 (21.3) 5 (0.9) &amp;lt;0.001 Right ventricular failure (%) 10 (1.9) 41 (19.8) 0 (0.0) &amp;lt;0.001 None Mitral regurgitation (%) 207 (42.2) 25 (12.6) 416 (81.2) &amp;lt;0.001 Moderate to severe mitral regurgitation (%) 258 (52.6) 143 (72.3) 92 (18) &amp;lt;0.001 Mitral Valve elongation (%) 113 (23.5) 48 (24.9) 62 (12.1) Abnormal insertion of a papillary muscle (%) 13 (2.7) 12 (6.2) 6 (1.2) Mitral valve SAM (%) 214 (40.8) 115 (55.6) 77 (14.2) &amp;lt;0.001 Basal obstruction (%) 196 (37.4) 119 (57.5) 54 (9.9) &amp;lt;0.001 Anteroposterior LA diameter (mm) (median [IQR]) 44.00 [38.00, 49.00] 47.00 [42.00, 51.00] 39.00 [33.00, 43.00] &amp;lt;0.001 Mitral E/e’ Lateral (median [QR]) 10.00 [8.00, 13.53] 15.00 [10.11, 20.00] 7.50 [5.80, 10.00] &amp;lt;0.001 Mitral E/e’ Septal (median [QR]) 15.00 [11.18, 19.55] 18.40 [14.20, 23.50] 10.50 [8.33, 13.88] &amp;lt;0.001 Normal sPAP (%) 354 (82.1) 74 (39.6) 435 (98.0) &amp;lt;0.001 Event AF (%) 80 (15.3) 60 (29.0) 27 (5.0) &amp;lt;0.001 Any cause death (%) 29 (5.5) 36 (17.4) 7 (1.3) &amp;lt;0.001 Any cause hospitalization (%) 174 (33.2) 113 (54.6) 56 (10.3) &amp;lt;0.001 3 different groups on their caracteristics and AF-risk Abstract Figure.

Comparison of catheter-directed thrombolysis and anticoagulation in intermediate-risk pulmonary embolism: A retrospective analysis

BACKGROUND AND OBJECTIVES: The selection of escalation of care strategies for the treatment of intermediate-risk pulmonary embolism (PE) is a matter of debate. Here, we aimed to assess the features of our population treated either with anticoagulation (AC) alone or catheter-directed thrombolysis (CDT). We also sought to identify a relationship between high residual systolic pulmonary artery pressure (sPAP) and demographic and clinical variables. PATIENTS AND METHODS: The retrospective data of 30 intermediate-high-risk PE patients were analyzed. CDT was used in 14 (46.7%) cases. Enoxaparin (b. i. d) injections were administered in the AC group. In the CDT group, patients received 5 mg bolus dose of alteplase followed by 1 mg/h infusion for 24 h. Estimated sPAP at presentation and discharge was recorded. A value equal to or greater than 40 mmHg in the latter was accepted as a significant rise. RESULTS: The patients in the CDT group had a lower HAS-BLED score (2 [0–3] vs. 1 [0–3], P = 0.03). Although initial sPAP values were comparable among treatment arms, sPAP at discharge was significantly lower in the CDT group (mmHg, 42 ± 11.2 vs. 33.6 ± 9.7, P = 0.04). The reduction in sPAP at discharge was also significantly higher in this group. The degree of reduction in sPAP was considerably correlated with baseline sPAP (r: 63.2, P CONCLUSION: CDT was preferred over AC when lower bleeding risk was anticipated for intermediate-high-risk PE patients in our sample population. Eventually, CDT provided lower discharge sPAP levels and a greater reduction in sPAP. However, the factors associated with high sPAP at discharge were only high baseline sPAP measurement and HAS-BLED score.

Disproportionate functional mitral regurgitation: clinical validation of a new conceptual framework

Abstract Background Disproportionate functional mitral regurgitation (FMR) is a novel concept that tries to identify hemodynamically significant FMR by readjusting the effective regurgitant orifice area (EROA) and regurgitant volume (RegVol) cut-offs according to left ventricular end-diastolic volume (LVEDV) and left ventricular ejection fraction (LVEF). However, this theoretical concept lacks clinical validation. The aim of this study was to assess the clinical significance of disproportionate FMR. Methods Patients with at least mild FMR and reduced LVEF (&amp;lt;50%) who underwent transthoracic echocardiography between 2010 and 2014 were retrospectively identified in our laboratory database. Optimal medical therapy (including cardiac resynchronization when indicated) for ≥3 months was a prerequisite for inclusion. Hemodynamically significant FMR was defined as regurgitant fraction &amp;gt;50% and the patient-specific theoretical RegVol cut-off was calculated according to the formula presented in Fig. 1a. The difference between the estimated RegVol by the PISA method and the theoretical RegVol cut-off was considered to represent the haemodynamic burden of MR. The primary endpoint was all-cause death. Patients were censured if mitral intervention or heart transplant was undertaken. Survival analysis was used to assess the effect of disproportionate FMR on mortality in 2 subgroups (LVEF &amp;lt;30% and 30–49%). Results A total of 289 patients (median age 69 years [IQR 60–77], 75% male, 53% of ischemic aetiology) were included. More than 90% were on beta-blockers and renin-angiotensin inhibitors, 44% on aldosterone receptor antagonists, and 73% had implanted devices. The median LVEF and LVEDV were 34% (IQR 27–41) and 170mL (IQR 128–220), respectively. Median EROA was 10mm2 (IQR 3–21) and RegVol was 15 mL (IQR 4–30). RegVol distribution across the cohort was: &amp;lt;10mL: 41%; 10–20mL: 18%; 20–30mL: 15% and &amp;gt;30mL: 26%. Disproportionate FMR was present in 83 patients (29%). These patients had significantly higher SPAP values (41mmHg [IQR 33–50] vs. 33mmHg [IQR 29–40]; p&amp;lt;0.001). During a median follow-up of 44 months (IQR 19–73), 106 patients died. In the LVEF &amp;lt;30% subgroup, age (HR 1.05 per year [1.02–1.08]; p&amp;lt;0.001), LVEF (HR 0.94 per 1% [0.89–0.99]; p=0.042) and TAPSE (HR 0.92 per mm [0.86–0.99]; p=0.030) were independent predictors of mortality. In the LVEF 30–49% subgroup, age (HR 1.05 per year [1.02–1.08]; p=0.003), LVEF (HR 0.94 per 1% [0.89–0.99]; p=0.020) and disproportionate FMR (HR 1.02 per mL [1.01–1.03]; p=0.01) were independently associated with increased mortality. Conclusions Disproportionate FMR proved to be an important independent predictor of mortality in patients with LVEF between 30–49%. These findings were not replicated in those with LVEF&amp;lt;30%, where the degree of biventricular dysfunction seems to outweigh all other echocardiographic parameters, leaving FMR as a bystander. Figure 1 Funding Acknowledgement Type of funding source: None

Association between serum levels of osteopontin and systolic pulmonary artery pressure among healthy adults post acute high altitude exposure

Objective: To explore the association between serum levels of osteopontin (OPN) and systolic pulmonary artery pressure (sPAP) in healthy men following acute high altitude exposure. Methods: According to the inclusion and exclusion criteria, this observational study included 94 male subjects (aged from 18 to 30 years, dwelling in lowland<500 m) who ascended to Litang (4 100 m) from Chongqing (400 m) by bus with a stair-like journey within 7 days in June 2013. Data including basic information, OPN, superoxide dismutase (SOD), and malondialdehyde (MDA) and echocardiographic derived sPAP were collected within 48 hours before ascent and within 2-7 hours after arrival. Accordingly, subjects were divided into 3 groups based on the tertiles of sPAP after acute high altitude exposure: low sPAP group (26.8-32.3 mmHg (1 mmHg=0.133 kPa)) (n=31), middle sPAP group (32.4-37.4 mmHg) (n=32) and high sPAP group (37.5-55.6 mmHg) (n=31). Associations of serum OPN and SOD levels with sPAP were analysed by univariate and multivariate linear regression analysis. Results: After acute high altitude exposure, the levels of sPAP were significantly increased (P<0.001). There were no differences in age, height, weight, body mass index, percent of Han nationality and smoking among 3 subgroups. However, following acute high altitude exposure, the levels of heart rate, systolic and diastolic blood pressure elevated (all P<0.05), whereas the levels of oxygen saturation were reduced in the total subjects and all subgroups (all P<0.05). Moreover, systolic blood pressure of subjects in the high sPAP group was higher than that in low and middle sPAP groups (both P<0.05), and diastolic blood pressure of subjects in high sPAP group was higher than that in low sPAP group (P<0.05). The serum levels of OPN were increased in total cohort(27.9 (22.5,34.0) μg/L vs. 25.6 (18.4, 33.1) μg/L, P<0.05)， and high sPAP group (P<0.05), whereas no differences were found in serum SOD and MDA levels among groups. Furthermore, the serum level of OPN in high sPAP group was higher than that in low sPAP group at high altitude (P<0.05), and there was a trend for decline in SOD level with increasing sPAP (P>0.05). Results from univariable linear regression analysis showed that the serum levels of OPN (r=0.32, P=0.002) and SOD (r=-0.22，P=0.032) were linearly correlated with sPAP in total cohort after high altitude exposure. Multivariate regression analysis showed that the serum levels of OPN(β=0.310，P=0.002) and SOD (β=-0.199，P=0.043) were independently associated with the levels of sPAP at high altitude. Conclusion: After acute high altitude exposure, the serum level of OPN is positively associated with sPAP, suggesting that OPN may be a novel bio-marker for predicting the increase of pulmonary pressure in response to acute high altitude exposure.

Value of Echocardiographic Right Ventricular and Pulmonary Pressure Assessment in Predicting Transcatheter Tricuspid Repair Outcome

ObjectivesThe aim of this study was to assess the value of echocardiographic right ventricular (RV) and systolic pulmonary artery pressure (sPAP) assessment in predicting transcatheter tricuspid edge-to-edge valve repair (TTVR) outcome. BackgroundRV dysfunction and pulmonary hypertension are associated with poor prognosis and are systematically sought during tricuspid regurgitation evaluation. The value of echocardiographic assessment in predicting TTVR outcome is unknown. MethodsData were taken from the TriValve (Transcatheter Tricuspid Valve Therapies) registry, which includes patients undergoing TTVR at 14 European and North American centers. The primary outcome was 1-year survival free from hospitalization for heart failure, and secondary outcomes were 1-year survival and absence of hospital admission for heart failure at 1 year. ResultsOverall, 249 patients underwent TTVR between June 2015 and 2018 (mean tricuspid annular plane systolic excursion [TAPSE] 15.8 ± 15.3 mm, mean sPAP 43.6 ± 16.0 mm Hg). Tricuspid regurgitation grade ≥3+ was found in 96.8% of patients at baseline and 29.4% at final follow-up; 95.6% were in New York Heart Association functional class III or IV initially, compared with 34.3% at follow-up (p < 0.05). Final New York Heart Association functional class did not differ among TAPSE and sPAP quartiles, even when both low TAPSE and high sPAP were present. Rates of 1-year survival and survival free from hospitalization for heart failure were 83.9% and 78.7%, respectively, without significant differences according to baseline echocardiographic RV characteristics (TAPSE, fractional area change, and end-diastolic area) and sPAP (p > 0.05 for all). ConclusionsTTVR provides clinical improvement, with 1-year survival free from hospital readmission >75% in patients with severe tricuspid regurgitation. Conventional echocardiographic parameters used to assess RV function and sPAP did not predict clinical outcome after TTVR.

Outcomes and Risk Factors of Systolic Pulmonary Artery Pressure Progression in Patients with Systemic Rheumatic Diseases: Follow-up Results from a Korean Registry.

Objectives This study aims to investigate the outcomes and risk factors associated with the progression of systolic pulmonary artery pressure (sPAP) in patients with systemic rheumatic diseases.Patients and methods A total of 532 patients (73 males, 459 females; median age 49 years; interquartile range (IQR), 36 to 62 years) registered with the Registry of Pulmonary Hypertension Associated with Rheumatic Diseases were included. Mortality curves were constructed using the Kaplan- Meier method and comparisons were performed using the log-rank test. A paired t-test was performed to evaluate the patients with markedly elevated sPAP between baseline and follow-up.Results The average follow-up duration was 31 months (IQR, 9 to 60 months). Of the patients, 196 had follow-up echocardiographs at least one year later. We defined the sPAP over 60 mmHg as markedly elevated. Patients in the increased sPAP above 60 mmHg at follow-up and persistently markedly elevated sPAP were associated with worse outcomes in all-cause mortality and pulmonary arterial hypertension-related mortality (p<0.001). In patients with systemic sclerosis, the majority of patients remained static within their pressure group or rose progressively: the patients with markedly elevated sPAP at follow-up were higher than those at baseline (32% versus 15%, p<0.01). In patients with mixed connective tissue disease (MCTD) or rheumatoid arthritis (RA), the majority of patients remained static within their pressure group or gradually improved: the patients with markedly elevated sPAP at follow-up were lower than those at baseline (RA=14% versus 29%, MCTD=5% versus 16%, p<0.05).Conclusion Persistently high sPAP or increase of sPAP over 60 mmHg at follow-up was associated with increased mortality. There were some differences in the progression of sPAP according to the underlying rheumatic diseases.

The role of parathyroid hormone and cardiac output in pulmonary hypertension in hemodialysis patients

Introduction: High prevalence of pulmonary hypertension has been reported in patients with chronic renal failure, especially those undergoing hemodialysis. Objectives: Considering the high prevalence of pulmonary hypertension in hemodialysis patients and uncertainty about the causes, the present study planned to investigate the role of parathyroid hormone (PTH) and cardiac ejection fraction (EF %) in development of pulmonary hypertension. Patients and Methods: By simple census sampling, all patients on hemodialysis in the hemodialysis center of Birjand University of Medical Sciences were enrolled. After obtaining written consent, the EF% and systolic pulmonary artery pressure (sPAP) were determined using echocardiography (MEDISON V10 model, Korea). The cut-point of less than 35 mm Hg was considered for normal sPAP. The blood sample was prepared to assay PTH using COBAS411 and ROCH kit. Independent t test or Man-Whitney test were used to compare means. P value &lt;0.05 was considered significant. Results: A totsl of 114 patients were enrolled in the study. Finally 89 patients, including 49 (55.1%) male and 40 (44.9%) female completed the study. The mean age and mean sPAP of the studied patients were 55.14 ± 15.68 years and 30.65 ± 12.10 mm Hg respectively. Among the studied patients, normal and high sPAP were reported in 60 (67.4%) and 29 (32.6%) cases respectively. Cardiac EF% in patients with normal and high sPAP was 59.08 ± 2.83 versus 56.37 ± 4.79 respectively (P = 0.01). PTH was determined 275.12 ± 218.44 versus 395.67 ± 332.05(pg/mL) (P = 0.03), in patients with normal and high sPAP respectively. Conclusion: The prevalence of pulmonary hypertension in the studied patients was 32.6%. Patients in the pulmonary hypertension group had higher levels of PTH and lower cardiac EF%.

P216 Cardiac amyloidosis is not a single disease: an echocardiographic study of light chain vs transthyretin forms

Abstract Background Cardiac amyloidosis (CA) is described as one entity. However, several subtypes of amyloid can infiltrate the heart: light chain (AL) and tranthyretin (ATTR) are the most common. Purpose To characterize the specific findings of the CA subtypes as a tool to aid differential diagnosis between AL and ATTR CA. Material and methods: Consecutive patients with CA were evaluated by clinical examination, ECG, cardiac biomarkers and echocardiography with both conventional and myocardial deformation study of the left ventricle (LV), left atrium (LA) and right ventricle (RV). Amyloid subtype was described using light chain assessment for AL-CA and 99Tc-HMPD scintigraphy and TTR gene sequencing for ATTR-CA. Results 32 patients with CA were included, 13 with ATTR and 19 with AL. Patients in AL group were significantly older, with higher levels of cardiac biomarkers. At similar LV EF and wall thickness, they had lower GLS. LA function parameters were also lower in AL pts (table). Using ROC curves, the best predictors for AL diagnosis were NTproBNP (AUC 0.937) and Tn levels (AUC 0.958), as well as LV GLS and pericardial fluid presence (both AUC 0.750). Conclusions At similar LV wall thickness and ejection fraction, cardiac dysfunction appears to be more severe in AL pts, with lower global LV longitudinal strain, worse LA function, higher sPAP and NTproBNP. ATTR (13 pts) AL (19 pts) p Age (years) 50 ± 12 60 ± 8 0.01 NTproBNP (pg/mL) 3066 ± 3720 11755 ± 9114 0.02 hsTnI (ng/mL) 0.005 ± 0.008 0.147 ± 0.161 0.04 Pericardial fluid (%) 53% 100% 0.002 LVEDV (mL) 88 ± 25 75 ± 38 NS LVMi (g/m2) 166 ± 47 168 ± 41 NS LVEF (%) 50 ± 8 49 ± 16 NS LV GLS (%) -12.1 ± 3.8 -8.9 ± 4.5 0.04 Septal Basal/Apical LS 0.33 ± 0.17 0.25 ± 0.27 NS LAVi (mL/m2) 46 ± 21 45 ± 14 NS LAEF 4CV (%) 35 ± 21 24 ± 8 0.05 LA systolic strain (%) 17.4 ± 11.9 10.5 ± 5.0 0.02 RV free wall thickness (mm) 7.0 ± 1.5 7.6 ± 1.4 NS RV 6-segments strain (%) -15 ± 4 -10 ± 8 0.09 sPAP (mmHg) 36.6 ± 12.0 48.6 ± 17.2 0.04

Abstract 17250: Underestimation of RV Volume by 3D Echocardiography in Patients With Severe PAH

Background: Right ventricular (RV) volume is a significant predictor of mortality in pulmonary arterial hypertension (PAH). RV volume measured by 3D echocardiography (3DE) an attractive imaging modality because it is faster and cheaper than cardiac MRIs. However, newer semi-automated speckle tracking 3DE has not been validated against cardiac MRI (CMR) in patients with severe PAH and dilated RVs. This study investigated the feasibility of 3DE to measure RV volumes in a prevalent cohort of patients with severe PAH. Methods: Patients with severe PAH with a 3DE and CMR within 30 days were included. RV endocardial contours were performed using TomTec 4D RV analysis© for 3DE and Circle Cardiovascular Imaging 42© for CMR. Results: Patients (n = 11) had severe PAH as classified as having high sPAP (66.4±5.0 mmHg), and reduced RV ejection fraction as measured by CMR (37.7±2.9%). In two patients, 3DE was not obtainable due to suboptimal definition of ventricular walls. In the remaining patients, there were systematic underestimation of volumes by 3DE (EDV bias: -71.5 LOA: 63.7; ESV -58.7: LOA: 72.7) and appears to be volume dependent (Fig 1A ). Lack of agreement seemed to possibly be related to extrapolation of poorly defined lateral wall RV endocardium by 3DE in patients with a large right ventricle (Fig 1B). Conclusion: Lack of agreement between CMR and 3DE derived RV volumes suggests the need for further validation of 3DE in patients with severe PAH.

Value of low-dose dobutamine stress echocardiography on defining true severe low gradient aortic stenosis in patients with preserved left ventricular ejection fraction

Low-dose dobutamine stress echocardiography (DSE) is a valuable tool to distinguish true-severe (TS) from pseudo-severe (PS) low gradient aortic valve stenosis (LGAS) in patients with reduced left ventricular ejection fraction (LVEF). However, only scanty studies reported the clinical utility of DSE in differentiating TS-LGAS patients with preserved LVEF. We investigated the clinical utility of DSE in LGAS patients with preserved LVEF and the echocardiographic determinants suggestive of TS-LGAS. 130 consecutive LGAS patients [indexed aortic valve area (AVA) ≤ 0.6cm2/m2 and mean trans-aortic pressure gradient (PGmean) < 40mmHg] with preserved (≥ 50%, n = 63) and reduced (< 50%, n = 67) LVEF were included. DSE defined TS-LGAS (projected AVA ≤ 1 cm2) in 61.2% patients with reduced LVEF and in 68.3% patients with preserved LVEF. Multivariate logistic regression analysis showed that baseline AVA was an independent determinant of TS-LGAS both in LVEF ≥ 50% (OR 0.45, P = 0.004) and LVEF < 50% groups (OR 0.55, P = 0.005). Reduced septal and lateral mitral annular plane systolic excursion (MAPSE, OR 0.72 and 0.75, P = 0.013 and 0.016) and septal TDI-s´ were significantly associated with TS-LGAS in patients with LVEF ≥ 50%. Higher systolic pulmonary artery pressure (SPAP, OR 1.43, P = 0.045) was associated with TS-LGAS in patients with LVEF < 50%. DSE is useful to define TS-LGAS also in patients with preserved LVEF. Lower baseline AVA values are linked with TS-LGAS in both patients with reduced and preserved LVEF. Reduced MAPSE and septal TDI-s´ are suggestive of TS-LGAS in patients with preserved LVEF, while higher SPAP is associated with TS-LGAS in patients with reduced LVEF.

Exhaled Nitric Oxide Changes During Acclimatization to High Altitude: A Descriptive Study.

This study describes differences in the partial pressures of exhaled nitric oxide (PeNO) between subjects fully acclimatized (ACC) to 5300 m and those who have just arrived to high altitude. PeNO was determined in eight subjects newly exposed and nonacclimatized (non-ACC) to high altitude and compared with that in nine subjects who had ACC to high altitude for 1 month. In addition, systolic pulmonary artery pressure (sPAP) and arterial oxygen saturation (SaO2) were measured in all participants. These measurements were repeated in the non-ACC group 5 and 9 days later. PeNO levels on day 1 were significantly higher in the non-ACC versus ACC cohort (8.7 ± 3.5 vs. 3.9 ± 2.2 nmHg, p = 0.004). As the non-ACC group remained at altitude, PeNO levels fell and were not different when compared with those of the ACC group by day 9 (5.9 ± 2.4 vs. 3.9 ± 2.2 nmHg, p = 0.095). Higher sPAP was correlated with lower PeNO levels in all participants (R = -0.50, p = 0.043). PeNO levels were not correlated with SaO2. As individuals acclimatized to high altitude, PeNO levels decreased. Even after acclimatization, PeNO levels continued to play a role in pulmonary vascular tone.

Prevalence and determinants or right ventricular dysfunction in severe aortic stenosis

Systolic pulmonary artery pressure (sPAP) is a well-known predictor of outcome in patients with valvular heart disease. In spite of this fact, limited data are available regarding the assessment of RV function in patients with aortic stenosis (AS). Aim of this study is therefore to evaluate the prevalence and the determinants of RV dysfunction in severe AS patients 301 patients (mean age: 79.7 ± 8.7, male sex 55.5%) with severe AS underwent 2D echocardiography and speckle tracking echocardiography (STE) for the evaluation of left ventricular and RV function, aortic valve gradients and sPAP. A tricuspid annular plane systolic excursion (TAPSE) ≤ 17 mm was used to define reduced RV ventricular function. RV function was impaired in 24% of patients (patients with reduced TAPSE had an impaired LV ejection fraction (LVEF) (49.2 ± 15.4 vs. 57.9 ± 10.9%, P < 0.0001), significantly altered STE parameters (GLS: −10.3 ± 3.9 vs. −13.2 ± 3.5%, GCS: −7.0 ± 3.0 vs. −10.4 ± 4.9%, GRS: 18.7 ± 11.6 vs. 28.4 ± 15.6, all P < 0.001) and a higher sPAP (48.4 ± 15.8 vs. 40.9 ± 12.7 mmHg, P = 0.002) with respec to patients with a normal RV function. Correlates of a reduced TAPSE were: LVEF ( β = 0.35, P < 0.0001), LV global longitudinal, circumferential and radial strain ( β = −0.40, β = −0.40, β = 0.37 respectively, all P < 0.0001), LV indexed stroke volume ( β = 0.44, s < 0.0001), lnNT-proBNP ( β = −0.51, P < 0.0001) and sPAP ( β = −0.27, P < 0.0001). At Kaplan-Meier survival curve, a TAPSE ≤ 17 mm was associated with a reduced survival in patients with AS (Log-Rank test, P = 0.034). In patients with severe AS, RV function impairment is frequent and is associated with a poor prognosis. The correlations of TAPSE highlight the RV-LV interdependence in AS patients. Further studies will clarify the real and independent prognostic value of RV function in severe AS patients and test for the RV reverse remodelling after treatment of the AS.