Normal Pulmonary Vascular Resistance Research Articles

The impact of ECPELLA on haemodynamics and global oxygen delivery: a comprehensive simulation of biventricular failure

BackgroundECPELLA, a combination of veno-arterial (VA) extracorporeal membrane oxygenation (ECMO) and Impella, a percutaneous left ventricular (LV) assist device, has emerged as a novel therapeutic option in patients with severe cardiogenic shock (CS). Since multiple cardiovascular and pump factors influence the haemodynamic effects of ECPELLA, optimising ECPELLA management remains challenging. In this study, we conducted a comprehensive simulation study of ECPELLA haemodynamics. We also simulated global oxygen delivery (DO2) under ECPELLA in severe CS and acute respiratory failure as a first step to incorporate global DO2 into our developed cardiovascular simulation.Methods and resultsBoth the systemic and pulmonary circulations were modelled using a 5-element resistance‒capacitance network. The four ventricles were represented by time-varying elastances with unidirectional valves. In the scenarios of severe LV dysfunction, biventricular dysfunction with normal pulmonary vascular resistance (PVR, 0.8 Wood units), and biventricular dysfunction with high PVR (6.0 Wood units), we compared the changes in haemodynamics, pressure–volume relationship (PV loop), and global DO2 under different VA-ECMO flows and Impella support levels.ResultsIn the simulation, ECPELLA improved total systemic flow with a minimising biventricular pressure–volume loop, indicating biventricular unloading in normal PVR conditions. Meanwhile, increased Impella support level in high PVR conditions rendered the LV–PV loop smaller and induced LV suction in ECPELLA support conditions. The general trend of global DO2 was followed by the changes in total systemic flow. The addition of veno-venous ECMO (VV-ECMO) augmented the global DO2 increment under ECPELLA total support conditions.ConclusionsThe optimal ECPELLA support increased total systemic flow and achieved both biventricular unloading. The VV-ECMO effectively improves global DO2 in total ECPELLA support conditions.

Pulmonary vascular dysfunction without pulmonary hypertension: A distinct phenotype in idiopathic pulmonary fibrosis.

Pulmonary vascular dysfunction in the absence of pulmonary hypertension (PH) has been observed in patients with idiopathic pulmonary fibrosis (IPF). We describe the prevalence and etiology of elevated pulmonary vascular resistance (PVR) without PH among patients with IPF. Hemodynamic, echocardiographic, and functional respiratory imaging (FRI) data was compared between patients with IPF without PH with normal (<3 wood units) and elevated PVR (≥3 wood units). Mortality between these two groups were compared to patients with IPF and PH. Of 205 patients with IPF, there were 146 patients without PH, of whom 114 (78.1%) had a normal PVR and 32 (21.9%) who had a high PVR. Functional testing and hemodynamics were similar in the two groups, except for the cardiac index which was significantly lower in patients with a high PVR (2.3 vs. 2.6 L/min/m2; p = 0.004). Echocardiographic comparison demonstrated a higher tricuspid regurgitant velocity in those with a high PVR (3.4 vs 3.0 m/s; p = 0.046). FRI revealed proportionately fewer large vessels as a proportion of the vasculature in the patients without PH and elevated PVRs. Among patients without PH, PVR was associated with increased mortality. In conclusion, patients with IPF without PH but a high PVR appear to be a distinct phenotype with a prognosis between those with and without PH, likely reflecting the continuum of vascular dysfunction. The basis for this unique hemodynamic profile could not be definitively discerned although FRI suggested an aberrant anatomical vascular response.

Factors influencing pulmonary arterial pressure in three related patients with Cantú syndrome: glyburide may provide precision care

A range of pulmonary arterial pressures was observed in three related patients with Cantú syndrome. The incident patient developed a moderately high pulmonary vascular resistance. Several factors influenced the severity of his pulmonary vascular disease and the events, which ultimately resulted in his death. However, he had an acute improvement in blood pressure and respiratory support after a single dose of glyburide when he was critically ill. The father and sister of the incident patient have evidence of mildly increased pulmonary arterial pressure with normal pulmonary vascular resistance. They are being treated with glyburide to potentially decrease the high cardiac output associated with a gain in KATP channel function. Additional experience with glyburide or other KATP channel inhibitors is needed to determine the most appropriate agent, dose, time, and duration of treatment for patients with Cantú syndrome.

Predictors of outcomes in mild pulmonary hypertension according to 2022 ESC/ERS Guidelines: the EVIDENCE-PAH UK study.

Interventional studies in pulmonary arterial hypertension completed to date have shown to be effective in symptomatic patients with significantly elevated mean pulmonary artery pressure (mPAP) (≥25 mmHg) and pulmonary vascular resistance (PVR) > 3 Wood Unit (WU). However, in health the mPAP does not exceed 20 mmHg and PVR is 2 WU or lower, at rest. The ESC/ERS guidelines have recently been updated to reflect this. There is limited published data on the nature of these newly defined populations (mPAP 21-24 mmHg and PVR >2-≤3 WU) and the role of comorbidity in determining their natural history. With the change in guidelines, there is a need to understand this population and the impact of the ESC/ERS guidelines in greater detail. A retrospective nationwide evaluation of the role of pulmonary haemodynamics and comorbidity in predicting survival among patients referred to the UK pulmonary hypertension (PH) centres between 2009 and 2017. In total, 2929 patients were included in the study. Patients were stratified by mPAP (<21 mmHg, 21-24 mmHg, and ≥25 mmHg) and PVR (≤2 WU, > 2-≤3 WU, and >3 WU), with 968 (33.0%) in the mPAP <21 mmHg group, 689 (23.5%) in the mPAP 21-24 mmHg group, and 1272 (43.4%) in the mPAP ≥25 mmHg group. Survival was negatively correlated with mPAP and PVR in the population as a whole. Survival in patients with mildly elevated mPAP (21-24 mmHg) or PVR (>2-≤3WU) was lower than among those with normal pressures (mPAP <21 mmHg) and normal PVR (PVR ≤ 2WU) independent of comorbid lung and heart disease [hazard ratio (HR) 1.36, 95% confidence interval (CI) 1.14-1.61, P = .0004 for mPAP vs. HR 1.28, 95% CI 1.10-1.49, P = .0012 for PVR]. Among patients with mildly elevated mPAP, a mildly elevated PVR remained an independent predictor of survival when adjusted for comorbid lung and heart disease (HR 1.33, 95% CI 1.01-1.75, P = .042 vs. HR 1.4, 95% CI 1.06-1.86, P = .019). 68.2% of patients with a mPAP 21-24 mmHg had evidence of underlying heart or lung disease. Patients with mildly abnormal haemodynamics were not more symptomatic than patients with normal haemodynamics. Excluding patients with heart and lung disease, connective tissue disease was associated with a poorer survival among those with PH. In this subpopulation evaluating those with a mPAP of 21-24 mmHg, survival curves only diverged after 5 years. This study supports the change in diagnostic category of the ESC/ERS guidelines in a PH population. The newly included patients have an increased mortality independent of significant lung or heart disease. The majority of patients in this new category have underlying heart or lung disease rather than an isolated pulmonary vasculopathy. Mortality is higher if comorbidity is present. Rigorous phenotyping will be pivotal to determine which patients are at risk of progressive vasculopathic disease and in whom surveillance and recruitment to studies may be of benefit. This study provides an insight into the population defined by the new guidelines.

C17 AN UNUSUAL CASE OF RIGHT HEART FAILURE AND PULMONARY HYPERTENSION: WET BERIBERI. THE IMPORTANCE OF DIFFERENTIAL DIAGNOSIS

Abstract Introduction High–output heart failure is a rare form of heart failure. Possible causes include vitamin B1 (thiamine) deficiency. This vitamin plays an important role in the aminoacids energy metabolism and in the transmission of nerve impulses. Thiamine deficiency can affect the cardiovascular (wet beriberi), nervous, and immune systems. Case report: This case report concerns a 73–year–old man with a history of alcohol abuse affected by arterial hypertension, persistent atrial fibrillation, COPD and alcoholic liver disease. Home therapy included low–dose diuretic, mineralocorticoid antagonists, anticoagulant, hypotensive drugs and oral antidiabetic drugs. Due to the occurrence of dyspnoea and progressive swelling of the lower limbs he was hospitalized. Transthoracic echocardiogram (TTE) showed mild biventricular dilatation with normal function. The Doppler study revealed moderate–severe tricuspid regurgitation (anulus dilatation) and indirect signs of an increase in pulmonary pressures. Blood tests showed a picture of cytopenia, altered hepatic synthesis indexes and high values of natriuretic peptides. He performed invasive hemodynamic evaluation with right heart catheterization which showed mild pulmonary hypertension (mPAP 28 mmHg) with normal pulmonary vascular resistance and an increase in cardiac index (CI 4.2 L/min/m2). The cardiopulmonary testing (CPET) indicated a slight reduction in functional capacity (pVo2 77% of predicted value) and initial pulmonary vascular involvement. In the following months the patient manifested haemodynamic instability with the need for intravenous diuretic therapy. At a subsequent check–up, the dosage of thiamin was performed, which was found to be deficient, so he started supplementation. In the next period the patient reported well–being and maintained euvolemia. At a hospital re–evaluation, he performed a new TTE evaluation which showed a reduction in ventricular volumes and tricuspidal regurgitation as well as a new evaluation of invasive cardiac output which showed a reduction in right sections pressure (mPAP 22 mmHg) with normalization of the CI value (2,20 L/min/m2). CPET showed almost the same results of the previous one. Conclusion Beriberi is a possible treatable cause of high–output heart failure. Although it is a rare pathology in Western countries, it should always be suspected in some categories of patients such as alcoholics, subjects with eating disorders and those undergoing bariatric surgery.

C47 ADAPTATION OF THE PULMONARY CIRCULATION AND OF THE RIGHT HEART IN INTRACARDIAC INVETERATE SHUNTS: UNDER PRESSURE OR LET IT FLOW?

Abstract Congenital heart disease can be associated with pulmonary hypertension (PH) development and heart right remodelling. Nevertheless, the adaptation of the pulmonary circulation and of the right heart can be extremely heterogeneous, so that an accurate diagnostic work up may be advisable when an intracardiac shunt is suspected. Case Presentation A 53 years old woman, with no relevant clinical history and asymptomatic, was incidentally found to have clinical, ECG and echocardiographic signs of PH, and was referred to our Center. Diagnostic and Therapeutic Work Up Echocardiography showed: normal left ventricle (LV 3D volumes 88/35 ml), mild left atrial dilatation (39 ml/m2); severe right chambers dilatation (RV 3D 347/124 ml, EF 3D 62%, AD 116 ml/m2), moderate tricuspid regurgitation with a regurgitant jet velocity of 2.9 m/s. Right heart catheterization showed normal pulmonary pressures at rest (mPAP 20, PAWP 5 mmHg), extremely high pulmonary blood flow (Qp 29 L/min, calculated with the direct Fick method), with normal pulmonary vascular resistance (PVR 0.5 WU). During the oxymetric run, a step up in hemoglobin saturation between superior vena cava and right atrium (from 74 to 97%) was found, with a Qp/Qs ratio of 5.5. During exercise, Qp reserve was normal, suggesting a normal contractile reserve function of RV despite the extreme dilatation. Additionally, the patient did not develop exercise PH and exercise capacity was normal, based on a measured oxygen consumption (VO2) at peak of 24 ml/kg/min (104% of predicted). Angio–CT of the chest was performed, confirming the presence of a sinus venosus atrial septal defect. The patient was then referred for surgical correction. Conclusion Echocardiography signs are useful to direct correctly diagnostic work up. A severe RV dilatation with normal systolic function in an asymptomatic middle age woman should raise the possibility of an intracardiac shunt. Despite a large intracardiac shunt with a high Qp/Qs ratio for decades, PVR was normal, confirming that individual predisposition may play a role in the development of PH in pre–tricuspid shunts. Exercise test showed an optimal RV reserve, suggesting a low cardiac surgery risk.

Shedding Light on Latent Pulmonary Vascular Disease in Heart Failure With Preserved Ejection Fraction

BackgroundAmong patients with heart failure with preserved ejection fraction (HFpEF), a distinct hemodynamic phenotype has been recently described, ie, latent pulmonary vascular disease (HFpEF-latentPVD), defined by exercise pulmonary vascular resistance (PVR) >1.74 WU. ObjectivesThis study aims to explore the pathophysiological significance of HFpEF-latentPVD. MethodsThe authors analyzed a cohort of patients who had undergone supine exercise right heart catheterization with cardiac output (CO) measured by direct Fick method, between 2016 and 2021. HFpEF-latentPVD patients were compared with HFpEF control patients. ResultsOut of 86 HFpEF patients, 21% qualified as having HFpEF-latentPVD, 78% of whom had PVR >2 WU at rest. Patients with HFpEF-latentPVD were older, with a higher pretest probability of HFpEF, and more frequently experienced atrial fibrillation and at least moderate tricuspid regurgitation (P < 0.05). PVR trajectories differed between HFpEF-latentPVD patients and HFpEF control patients (Pinteraction = 0.008), slightly increasing in the former and reducing in the latter. HFpEF-latentPVD patients displayed more frequent hemodynamically significant tricuspid regurgitation during exercise (P = 0.002) and had more impaired CO and stroke volume reserve (P < 0.05). Exercise PVR was correlated with mixed venous O2 tension (R2 = 0.33) and stroke volume (R2 = 0.31) in HFpEF-latentPVD patients. The HFpEF-latentPVD patients had had higher dead space ventilation during exercise and higher PaCO2 (P < 0.05), which correlated with resting PVR (R2 = 0.21). Event-free survival was reduced in HFpEF-latentPVD patients (P < 0.05). ConclusionsThe results suggest that when CO is measured by direct Fick, few HFpEF patients have isolated latent PVD (ie, normal PVR at rest, becoming abnormal during exercise). HFpEF-latentPVD patients present with CO limitation to exercise, associated with dynamic tricuspid regurgitation, altered ventilatory control, and pulmonary vascular hyperreactivity, portending a poor prognosis.

111 POST-OPERATIVE OUTCOME OF ADULT PATIENTS WITH PRE-TRICUSPID SHUNT UNDERGOING DEFECT CLOSURE

Abstract Background patients with pulmonary arterial hypertension (PAH) associated with corrected congenital heart disease (CHD) have a worse prognosis than other 3 groups of patients with PAH associated with CHD (Eisenmenger, small defect, prevalent systemic-to-pulmonary shunt). For this reason, in CHD the indication and timing of defect repair should be evaluated carefully. Current recommendations rely essentially on pulmonary vascular resistance (PVR) when deciding about defect closure, but this may be insufficient as PAH may develop even in cases of normal pre-operative PVR. In particular, patients with PVR below 3 WU are usually deemed operable and patients between 3 and 5 WU (gray zone) are deemed operable in case of significant persistence of left-to-right shunt. Detecting preoperative characteristics of patients who developed PAH after pre-tricuspid shunt repair can be helpful when deciding about CHD correction. Methods we enrolled adult patients referred to our centre for the suspicious of PAH after pre-tricuspid shunt correction from 2006 to 2021. We evaluated clinical, echocardiographic and hemodynamic parameters before and after defect repair (a post-correction hemodynamic evaluation was performed only in case of non-invasive signs of PAH) and PAH after defect closure was defined by the concomitant occurrence of a mean pulmonary artery pressure (mPAP) &amp;gt;25 mmHg and PVR &amp;gt;3 WU. Continuous variables were summarized using mean and standard deviation and Student's t-test was used for comparisons. Results sixty patients were included in the final analysis. After shunt repair, 10 patients (16.6%) were diagnosed with PAH during the long-term follow-up, with no differences given by the type of defect or type of correction. As expected, these patients already had an abnormal baseline hemodynamic profile: 7 had a clear PAH diagnosis before the correction [mPAP &amp;gt;25 mmHg with PVR between 3 and 5 WU and with a pulmonary/systemic cardiac output ratio of at least 1.5] while 3 had pulmonary hypertension related to high pulmonary blood flow (mPAP &amp;gt;25 mmHg and PVR &amp;lt;3 WU). At the baseline hemodynamic evaluation, patients with PAH after shunt repair had higher mPAP (39±6 vs 24±10 mmHg, p &amp;lt;0.001) and PVR (3.7±1.2 vs 1.5±0.9, p &amp;lt;0.001) and lower mixed venous oxygen saturation (81±3 vs 87±3, p &amp;lt;0.001). At the baseline echocardiographic evaluation, patients with PAH after shunt repair had a greater right ventricular hypertrophy (RV wall thickness 0.7±0.1 vs 0.5±0.2 cm, p= 0.011), tricuspid regurgitation jet velocity (424±63 vs 319±62 cm/s, p &amp;lt;0.001) and a significant lower RV fractional area change (34±8 vs 43±9%, p= 0.009). Conclusions currently there are no established evidence-based algorithms to predict the development of PAH after defect correction. Our study shows that this condition may persist or develop even when PVR values are lower than 5 WU despite a significant left-to-right shunt before defect closure. Patients with grey zone PVR values require a global clinical, instrumental and hemodynamic assessment that takes into account more than bare calculated PVR that, especially in patients with a high pulmonary blood flow, can be less reliable.

Abstract 13710: Acute Beneficial Effects of a Rho-Kinase Inhibitor, Fasudil in Patients With Pulmonary Hypertension Due to Left Heart Disease

Introduction: The prognosis of reactive pulmonary hypertension (PH) due to left heart disease is poor, and the pathogenesis of the disease is not well understood. Rho-Kinase inhibitor, fasudil dilates vascular smooth muscle and may improve pulmonary hypertension. We evaluated the acute effects of fasudil on hemodynamic parameters in patients with pulmonary hypertension due to left heart disease prospectively. Methods: From 2016 June to 2022 May, 100 consecutive patients requiring hospitalization for worsening chronic heart failure were enrolled. All patients underwent invasive hemodynamic measurement though right heart catheterization.In patients with mean pulmonary arterial pressure greater than 25 mmHg at baseline, 30 mg of fasudil was administered intravenously for 30 minutes. The hemodynamic measurements were performed at baseline and after 30 minutes of fasudil. PH due to left heart disease is defined as mean pulmonary arterial pressure (mPAP) ≥25mmHg and mean pulmonary capillary wedge pressure (mPCWP) &gt;15mmHg. Patients with PH were classified into 2 types, depending on the elevation of pulmonary vascular resistance (PVR) or the diastolic pressure gradient (DPG): Reactive-PH with elevated PVR (&gt;3.0 Wood units: WU) and/or DPG (&gt;7mmHg), and Passive-PH with normal PVR (≤3.0 WU) and DPG (≤7mmHg). Results: Fifty patients (mean age 70 years; 14 women and 36 men) received administration of fasudil. 30 patients had Passive-PH, and 20 patients had Reactive-PH. PVR significantly decreased after administration of fasudil in both Passive-PH and Reactive-PH group (1.7 to 1.4 WU, 3.5 to 2.7 WU, P&lt;0.001). The rate of change in PVR after administration of fasudil was significantly higher in the Reactive-PH group compared to the Passive-PH group (33% vs 21 %, P&lt;0.05). mPAP and cardiac index significantly improved in both Passive-PH (34±8.5 vs. 28±8.2 mmHg, 2.7±0.7 vs. 2.9±0.8 l/min/m 2 , p&lt;0.05) and Reactive-PH group (41±7.9 vs. 33±9.0 mmHg, 2.2±0.6 vs. 2.4±0.6 l/min/m 2 , p&lt;0.05). Mean blood pressure and arterial oxygen saturation were unaffected by fasudil (87 to 84 mmHg, 99 to 90 mmHg, 98 to 97%, 97 to 97%, not significant). Conclusions: Fasudil improves pulmonary hypertension due to left heart disease without any detrimental effects on hemodynamics.

Mortality rates and cause of mortality in patients with mildly elevated pulmonary pressures versus PH: insights from the retrospective EVIDENCE-PAH study

Abstract Background Normal mean pulmonary artery pressure (mPAP) does not exceed 20 mmHg and normal pulmonary vascular resistance (PVR) does not exceed 2 Wood Units (WU). The thresholds used to define pre-capillary pulmonary hypertension (PH) – mPAP ≥25 mmHg and PVR &amp;gt;3 WU – are being evaluated. It is unclear if treatment would benefit patients with mildly elevated mPAP (≥21–&amp;lt;25 mmHg). Purpose The EVIDENCE-PAH study aims to describe mortality and hospitalisation outcomes, clinical characteristics, therapies, and quality of life during long-term follow-up of a national cohort of patients with different levels of mPAP and PVR. We report preliminary analyses focusing on mortality and its cause in patients stratified by their baseline (BL) mPAP. Methods This retrospective analysis included PAH-treatment-naïve patients with suspected PH who received a first right heart catheterisation (RHC) between 2009 and 2017 at any of the 7 UK tertiary PH centres, which assess all PH patients in the UK. A sample of patients with BL mPAP ≥25 mmHg (stratified by PVR and treatable versus non-treatable PH) was used as a control in this analysis. Baseline characteristics, mortality and cause of mortality were stratified by mPAP (&amp;lt;21, ≥21–&amp;lt;25, ≥25 mmHg) at BL (first RHC). Mortality was also stratified by BL PVR (&amp;lt;1, 1–&amp;lt;2, 2–&amp;lt;3, 3–&amp;lt;6, ≥6 WU). Mortality analysis was done without matching cohorts. Mortality data were obtained from the Office for National Statistics, NHS Digital. Results In total, 2926 patients were analysed (968, 689 and 1269 with mPAP &amp;lt;21, ≥21–&amp;lt;25, ≥25 mmHg, respectively). Mean observation was 6.1 years. BL characteristics are in Table. Survival worsened with increasing mPAP (p&amp;lt;0.0001) and increasing PVR (p&amp;lt;0.01) (Figure). After 5 years of follow-up, 187 (27.1%) patients with mPAP ≥21–&amp;lt;25 mmHg had died, compared with 162 (16.7%) and 595 (46.9%) patients in the lower and higher mPAP groups, respectively. In patients with mPAP ≥21–&amp;lt;25 mmHg, the most common main cause of death was respiratory disease (36.4%) – with scleroderma lung disease and interstitial lung disease accounting for 69.1% of these deaths – followed by cardiac disease (16.6%) and malignancy (15.0%) (Table). PH was the main cause of death for only 1.6% of patients with mildly elevated mPAP and it was a contributor to death in 6.8% (BL mPAP &amp;lt;21 mmHg), 10.2% (≥21–&amp;lt;25 mmHg), and 40.2% (≥25 mmHg) of cases. Conclusion Long-term survival in patients with mPAP ≥21–&amp;lt;25 mmHg was worse than in those with normal mPAP, and better than in those with the current definition of PH. While the main cause of death was mostly unrelated to PH and further analysis is needed to understand the impact of underlying disease, mildly elevated mPAP appears to confer a worse prognosis and should be closely monitored. These data show the relevant disease burden in patients with mPAP ≥21–&amp;lt;25 mmHg and the need to understand if they could benefit from treatment. PVR may be key in determining patients who might benefit. Funding Acknowledgement Type of funding sources: Private company. Main funding source(s): Actelion Pharmaceuticals Ltd., a Janssen pharmaceutical company of Johnson &amp; Johnson.

Prognostic impact of echocardiographic derived precapillary wedge pressure and pulmonary vascular resistances in patients with heart failure

Abstract Background A reliable echocardiographic algorithm for the estimation of precapillary wedge pressure (PCWP) and pulmonary vascular resistances (PVR) has been recently validated by our group in a large cohort of patients undergoing right heart catheterization (RHC) (1). Those metrics may add relevant clinical and prognostic information in patients with heart failure (HF). Objective To assess the clinical/prognostic significance of echocardiographic derived PCWP and PVR in a large cohort of chronic HF patients on modern treatments. Methods Outpatients with chronic HF with either reduced (≤40%) or mildly reduced LVEF (41–49%) underwent a thorough clinical multiparametric assessment and were followed-up for a composite endpoint of cardiac death, appropriate ICD shock, or first HF hospitalization. Results Out of 1,483 patients prospectively enrolled (70±12 years, 73% males, 42% ischemic etiology, LVEF 35±8%), PCWP (16.4±5.8 mmHg) was elevated (&amp;gt;15 mmHg) in 53% of cases, while PVR (1.7±0.7) was elevated (&amp;gt;3 WU) in 6% of cases. Of the latter group, most (92%) had also elevated PCWP. Patients with increased PCWP were older, had a higher heart rate and lower cardiac output, showed a higher degree of left and right chamber remodeling, had a higher neurohormonal activation, worse renal function, worse functional capacity and ventilatory efficiency on effort (all p&amp;lt;0.001). Those patients with high PCWP and PVR showed higher heart rate and pulmonary pressures, lower cardiac output, and right ventricular function, higher neurohormonal activation, lower functional capacity and ventilatory efficiency on effort compared to patients with high PCWP but normal PVR (all p&amp;lt;0.01). The optimal prognostic cut-point was identified for both PCWP (16.2 mmHg) and PVR (2 WU) by log-rank maximal likelihood ratio. Over a median follow-up of 22 (8–37) months, both measures significantly stratified patients for the risk of the primary endpoint at Kaplan-Meier analysis (log-rank 92.9, p&amp;lt;0.001 for PCWP; log-rank 17.3, p&amp;lt;0.001 for PVR). At multivariable Cox regression analysis (adjusted for age, sex, ischemic HF etiology, renal function, LVEF, and NT-proBNP), PCWP (hazard ratio, HR 1.77 [95% CI 1.30–2.40], p&amp;lt;0.001) but not PVR (HR 1.15 [95% CI 0.88–1.51], p=0.31) remained an independent predictor of the primary outcome. Conclusion The estimation of PCWP and PVR by echocardiography add relevant clinical and prognostic information and may help in the decision making in patients with HF. Funding Acknowledgement Type of funding sources: None.

P245 A RARE CAUSE OF OVERESTIMATION OF PULMONARY PRESSURE BY ECHOCARDIOGRAPHY: WHEN HEMODYNAMICS RELIEVES ECHOCARDIOGRAPHY AND ECHOCARDIOGRAPHY EXPLAINS HEMODYNAMICS

Abstract Echocardiography is the gatekeeper of the diagnostic workflow of pulmonary hypertension (PH). However, it lacks precision, and right heart catheterization (RHC) may be needed in selected cases. A morbidly obese 47–year–old woman (BMI= 58 Kg/m2) with dyspnea NYHA II was referred to our Center after a high probability of PH was found at echocardiography, this latter performed as a routine assessment before bariatric surgery. Despite a suboptimal acoustic window, the tricuspid regurgitant jet profile was well–defined, with an estimated systolic pulmonary artery pressure (PAP) of 100 mmHg. There were no overt echocardiographic signs of left heart disease. During RHC, mean PAP was just above normal values, with filling pressures at the upper limit of normal (Figure 1), high cardiac index (3.6 L/min/m2) and normal pulmonary vascular resistance (1.4 WU). The echocardiographic estimate of high systolic PAP was explained by an intraventricular RV pressure gradient of about 100 mmHg (Figure 2). Oximetry ruled out a significant intracardiac shunt. Since resting hemodynamics did not explain the patient’s symptoms, the patient pre–test probability of having heart failure with preserved ejection fraction (HFpEF) was intermediate–high, and PAWP was in a grey–zone. Accordingly, we performed an exercise RHC. The test eventually unmasked HFpEF, as witnessed by an abnormal increase of PAWP and LV end–diastolic pressure (Figure 1 panel C and D). Exercise capacity was mildly reduced (71% of predicted) due to peripheral limitation with normal cardiac and respiratory reserves. Transesophageal echocardiography was then performed. It showed a muscular obstruction below the infundibulum dividing the RV into a high–pressure apical portion and a low–pressure infundibulum (Figure 3). This rare congenital anomaly was also associated with a restrictive perimembranous ventricular septal defect. Double–chambered RV has been reported to present rarely in adults, but it might be a cause of false Doppler echocardiographic estimate of PAP. Based on a meticulous invasive hemodynamic characterization at rest and during exercise, integrated with cardiovascular imaging, we could perform such a diagnosis. This congenital anomaly did not fully explain the patient’s symptoms, which may better be attributed to cardiovascular complication of obesity (HFpEF). Accordingly, we referred the patient for bariatric surgery first, postponing the indication to cardiac surgery during the follow–up.

P314 WHEN TAKO–TSUBO TRAPS… NOT ONLY OCTOPUSES

Abstract The case we present involves a 75 years–old woman with no cardiological past medical history, who presented to our attention complaining of sudden onset thoracic pain associated with dyspnea, dry cough, nausea and an episode of vomit. She called 911 rapidly coming to our Hospital. In the Emergency room an EKG showed ST segment depression in the inferior leads and in the blood test a remarkable increase in HS–Troponin level was evident. An echocardiogram showed mid and apical left ventricle segments hypokinesia with moderately reduced Ejection Fraction (45%); notably, right ventricle was increased in dimension with moderate tricuspid regurgitation and mild pulmonary hypertension. Because of this last find, D–dimer was checked and a pulmonary angio– CT was performed which excluded active pulmonary embolism. Next day she underwent coronary angiography which showed no coronary lesion able to explain the clinical and echocardiographic presentation; left ventriculography was also performed showing an increase in end–systolic volume with hypokinesia of the anterolateral, apical and diaphragmatic walls and an Ejection Fraction (EF) of 30%. These findings allowed us to make the diagnosis of Tako–Tsubo syndrome, also known as stress–induced cardiomyopathy. Few days later, a cardiac magnetic resonance (CMR) was performed showing whole apical and antero–lateral mid ventricular hypokinesia with compensatory hyperkinesia of basal segments; T2–weighted sequences were positive at the hypokinetic segments with no specific Late Gadolinium Enhanced (LGE) images. What’s more, an atrial septal defect type “ostium secundum” was clearly evident, causing a left–to–right shunt hemodynamically significant (Qp/Qs of about 2,8) with right atrial and right ventricle dilatation. Pulmonary artery and its main branches were dilated too. After these findings, lady underwent right heart cardiac catheterization that reported a Qp/Qs of 3,24 and a shunt flow of 8,78 L/min, with a cardiac index of 2,5 L/min/m2 and normal pulmonary vascular resistance (0,7 Wood Units). Because of these measures the patient was discharged from our Cardiology Unit and referred to the Interventional Cardiology centre of our city for the percutaneous closure of the hemodynamically significant atrial septal defect. This case is curious because it shows how things in Cardiology can be deeply and unpredictably connected.

Hemodynamic Changes After Left Ventricular Assist Device Implantation Among Heart Failure Patients With and Without Elevated Pulmonary Vascular Resistance

BackgroundLeft ventricular assist devices (LVADs) may reverse elevated pulmonary vascular resistance (PVR) which is associated with worse prognosis in heart failure (HF) patients. We aim to describe the temporal changes in hemodynamic parameters before and after LVAD implantation among patients with or without elevated PVR.MethodsHF patients who received continuous-flow LVAD (HeartMate 2&3) at a tertiary medical center and underwent right heart catheterization with PVR reversibility study before and after LVAD surgery. Patients were divided into 3 groups: normal PVR (<4WU); reversible PVR (initial PVR ≥4WU with positive reversibility); and non-reversible (persistent PVR ≥4WU).ResultsOverall, 85 LVAD patients with a mean age of 58 years (IQR 49–64), 65 patients (76%) were male; 60 patients had normal PVR, 20 patients with reversible and 5 patients with non-reversible PVR pre-LVAD. All patients with elevated PVR (≥4WU) had higher pulmonary pressures (PP) and increased trans-pulmonary gradient (TPG) compared to patients with normal PVR (p < 0.05). Patients with non-reversible PVR were more likely to have a significantly lower baseline cardiac output (CO) compared to all other groups (p ≤ 0.02). Hemodynamic parameters and PVR post LVAD were similar in all study groups. Patients with baseline elevated PVR (reversible and non-reversible) demonstrated a significant improvement in PP and TPG compared to patients with normal baseline PVR (p ≤ 0.05). The improvement in CO and PVR post-LVAD in the non-reversible PVR group was significantly greater compared to all other groups (p < 0.01). There were no significant differences between study groups in post LVAD and post heart transplantation course.ConclusionHemodynamic parameters improved after LVAD implantation, regardless of baseline PVR and reversibility, and enabled heart transplantation in patients who were ineligible due to non-reversible elevated PVR. Our findings suggest that mitigation of elevated non-reversible PVR is related to reduction in PP and increase in CO.

Not All Ventricular Arrhytmias Require A Reduction In LVAD Speed.

Background Despite hemodynamic optimization, ventricular arrhythmias following left ventricular assist device (LVAD) may persist. We present a case in which transthoracic echocardiogram (TTE) paired with LVAD waveform analysis at time of ventricular arrhythmias assisted in differential diagnosis for the precipitating etiology and helped guide management decisions. Case A 78-year-old African American male with stage D heart failure due to ischemic cardiomyopathy underwent implantation of a HeartWare LVAD. Post-operatively, the patient was weaned off inotropes and pressors with gradual speed adjusted to 2600 rpm over the course of a week. Following optimization, he had several episodes of ventricular tachycardia and ventricular fibrillation requiring defibrillation. The likely etiology of trigger was from a fascicular based premature ventricular contraction or suck down event from speed optimization. Intracardiac hemodynamics with Swan-Ganz catheter revealed normal filling pressures, cardiac index and pulmonary vascular resistance with low suspicion for right ventricular failure. An echocardiogram was without evidence of cardiac tamponade. Furthermore, at the time of TTE, another ventricular arrhythmia was captured (Figure 1). The inflow cannula was visualized to be well-positioned and there was no suction event, despite the ongoing arrhythmia. The left ventricle was not excessively decompressed either with an LVIDD at 4.9 cm with speed increased to 2700 rpm. HeartWare waveforms were visualized real-time without evidence of speed drops or alarms. The patient remained hemodynamically stable with a mean arterial pressure of 78 mmHg. He was successfully managed with metoprolol and sotalol. Conclusion Real-time waveforms on LVAD paired with a TTE can aide in the management in patients with ventricular arrhythmias. As this case demonstrates, not all ventricular arrhythmias merit a reduction in speed, particularly in those patients with normal pulmonary vascular resistance. Despite hemodynamic optimization, ventricular arrhythmias following left ventricular assist device (LVAD) may persist. We present a case in which transthoracic echocardiogram (TTE) paired with LVAD waveform analysis at time of ventricular arrhythmias assisted in differential diagnosis for the precipitating etiology and helped guide management decisions. A 78-year-old African American male with stage D heart failure due to ischemic cardiomyopathy underwent implantation of a HeartWare LVAD. Post-operatively, the patient was weaned off inotropes and pressors with gradual speed adjusted to 2600 rpm over the course of a week. Following optimization, he had several episodes of ventricular tachycardia and ventricular fibrillation requiring defibrillation. The likely etiology of trigger was from a fascicular based premature ventricular contraction or suck down event from speed optimization. Intracardiac hemodynamics with Swan-Ganz catheter revealed normal filling pressures, cardiac index and pulmonary vascular resistance with low suspicion for right ventricular failure. An echocardiogram was without evidence of cardiac tamponade. Furthermore, at the time of TTE, another ventricular arrhythmia was captured (Figure 1). The inflow cannula was visualized to be well-positioned and there was no suction event, despite the ongoing arrhythmia. The left ventricle was not excessively decompressed either with an LVIDD at 4.9 cm with speed increased to 2700 rpm. HeartWare waveforms were visualized real-time without evidence of speed drops or alarms. The patient remained hemodynamically stable with a mean arterial pressure of 78 mmHg. He was successfully managed with metoprolol and sotalol. Real-time waveforms on LVAD paired with a TTE can aide in the management in patients with ventricular arrhythmias. As this case demonstrates, not all ventricular arrhythmias merit a reduction in speed, particularly in those patients with normal pulmonary vascular resistance.

Ventricular Assist Device (VAD) Implantation in a Patient with Complex Congenital Heart Disease (CHD)

<h3>Introduction</h3> VAD implantation in complex CHD patients presents physiologic and anatomic challenges. Few such cases have been described. <h3>Case Report</h3> We report a 41-year-old man with a history of dextrocardia, unbalanced atrioventricular (A-V) septal defect, single ventricle, heterotaxy with right atrial isomerism and asplenia, bilateral superior vena cava, pulmonic stenosis, and systemic hypertension. He had undergone surgical palliation including bilateral BT shunts (age 3 months and 7 years) and central aortopulmonary shunt at age 13 years. At age 14 years, he underwent bilateral bidirectional Glenn and extracardiac Fontan repair, followed by mechanical A-V valve replacement at age 21 years and epicardial pacemaker placement for paroxysmal atrial tachycardia (AT). He had recurrent heart failure hospitalizations requiring inotropes. Echocardiography now demonstrated moderate aortic regurgitation. Cardiac catheterization on milrinone and dobutamine found elevated Fontan pressures to 21 mmHg (panel A), reduced cardiac index to 1.4 L/min/m², normal pulmonary vascular resistance and no transhepatic gradient. An intra-aortic balloon pump was placed with improvement of his Fontan pressures to 17 mmHg. However, he subsequently developed refractory AT and cardiogenic shock. Due to cardiac deterioration, he underwent urgent HeartMate3 implantation and aortic valve repair with Park stitch (B: pre-op; C: post-op image) as a bridge to transplant. Surgical approach was an upper hemisternotomy and an anterior right thoracotomy at the 6th intercostal space. His course was complicated by postoperative bleeding requiring re-exploration of the chest, as well as acute kidney injury requiring temporary hemodialysis with subsequent renal recovery. He was transferred to acute rehab 3 weeks after surgery and was discharged home on guideline-directed medical therapy. <h3>Summary</h3> We report an adult patient with dextrocardia, Fontan repair, and single ventricle who underwent successful VAD implantation.

Intrahepatic Portosystemic Shunt In Cardiac Amyloidosis: Turning Off The Faucet Leads To Resolution Of Hepatic Encephalopathy And Improvement In Heart Failure Symptoms

<h3>Introduction</h3> Spontaneous portosystemic shunts (SPSS) are extremely rare and usually extrahepatic due to portal hypertension in the setting of cirrhosis. Current knowledge regarding SPSS in adults in the absence of cirrhosis is limited. The implications of SPSS in patients with transthyretin amyloid cardiomyopathy (ATTR-CM) are unknown. <h3>Case</h3> A 76-year-old man with a history of HTN, CAD and systolic dysfunction (EF 45%) presented to the hospital with symptoms of HF exacerbation and cognitive dysfunction. Initial cardiac labs were notable for a borderline elevated troponin and high natriuretic peptic level. Hepatic labs were notable for mild elevation in transaminases, thrombocytopenia and an elevated ammonia level. Transthoracic echocardiogram (TTE) revealed that the EF was stable at 45%, but there was biatrial enlargement and progression of concentric LVH to 1.8cm and resultant small LV cavity (EDV index 39ml/m²), suspicious for infiltrative cardiomyopathy (Fig A). SPEP/UPEP with immunofixation and serum free light chains were normal and Tc-99m PYP study was consistent with ATTR-CM (Fig B). Abdominal US revealed a large intrahepatic venous shunt from the right portal vein to the right hepatic vein. Right heart catheterization, portal venogram and liver biopsy revealed a right atrial pressure of 14mmHg, cardiac output of 6.2L/min, normal pulmonary vascular resistance, hepatic vein pressure of 14mmHg, portal vein pressure of 15mmHg, confirmation of the large SPSS (Fig C) and no evidence of cirrhosis. The patient underwent embolization of the SPSS with a 22mm vascular plug (Fig D). Following closure, the patient's HF symptoms and HE improved dramatically and his abnormal hepatic labs normalized. He was started on a stabilizer for the treatment of his ATTR-CM. At one year, he has not had recurrent symptoms of HE, nor repeat hospitalization for HF exacerbation. <h3>Discussion</h3> This patient most likely had a SPSS that only manifested clinically in the setting of elevated right atrial and hepatic pressures due to the development of ATTR-CM. Ultimately, the decision was made to close the SPSS for two reasons. The first was to treat HE—in the same way that transjugular intrahepatic portosystemic shunt (TIPS) procedure can cause HE and subsequent TIPS closure can be an effective treatment for refractory HE. The second was to improve HF symptoms. Although this patient's cardiac output was "normal", it was likely actually high in the context of the severe LVH and small LV cavity due to ATTR-CM and the increased venous return was poorly tolerated given the underlying restrictive cardiomyopathy.

Meeting abstracts from the 15th international conference on neonatal and childhood pulmonary vascular disease

Meeting abstracts from the 15th international conference on neonatal and childhood pulmonary vascular disease

EP188: Novel HECW2 variant presenting with tachypnea and multisystemic congenital malformations

HECW2, otherwise known as NEDL2, encodes for a member of the HECT family of E3 ubiquitin ligases and stabilizes p73, a key mediator in neurodevelopment. HECW2 is primarily expressed in the brain, heart, and lungs. Heterozygous variants have been associated with developmental delays, intellectual disability, epilepsy, hypotonia, scoliosis and dysmorphic features. Systemic complications which have been reported include cardiomyopathy, skeletal abnormalities including pectus excavatum, and various brain abnormalities including white matter disease, cortical atrophy, ex-vacuo ventriculomegaly, and thinning of the corpus callosum. While many reported cases of HECW2-related disorder have been from de novo variants, there have been reports of familial inheritance with variable expressivity. To date, there have been no reported cases of HECW2-related disorder presenting with persistent tachypnea. A newborn male with a history of intrauterine growth restriction born at 39 2/7 weeks gestation to a 31 year old G4P0212 mother and a 35 year old father presented in the perinatal period with unexplained persistent tachypnea, difficulty feeding, persistent diaphoresis and failure to thrive. Pectus excavatum was noted at birth and initial evaluation for the persistent tachypnea showed multiple vertebral anomalies, congenital scoliosis and mild cardiomegaly on chest X-ray. Renal ultrasound demonstrated left central calyceal dilation. Echocardiogram and CT heart with contrast demonstrated multiple abnormalities including anomalous pulmonary venous return with right upper pulmonary vein draining into the superior vena cava (SVC), secundum atrial septal defect (ASD), dilated main pulmonary artery, right atrium and ventricle, mild right and left ventricular hypertrophy, mild tricuspid regurgitation and mild to moderate pulmonary regurgitation. CT imaging also demonstrated severe tracheobronchomalacia associated with left mainstem bronchus compression resulting in air trapping within the left lung. Cardiac catheterization was attempted for possible closure of the patient’s secundum ASD, but was unsuccessful due to inability to capture retroaortic rim. Diagnostic evaluation during catheterization demonstrated mild pulmonary hypertension, normal pulmonary vascular resistance (PVR) and a Qp:Qs of 1.9:1 consistent with pulmonary overcirculation. Tachypnea and significantly increased work of breathing persisted despite initiation of furosemide diuresis to manage pulmonary overcirculation. The patient ultimately required BiPap for respiratory support, though tachypnea persisted. A G-tube was placed to ensure safe formula administration. Additional physical exam findings included hypotonia, macrocephaly, infraorbital creases with almond-shaped eyes, ocular hypertelorism, broad nasal bridge and tip, mild retrognathia, arachnodactyly with larger hands and feet compared to growth centiles and Y-shaped gluteal fold. Family history was remarkable for White ancestry. A maternal half-sister was healthy. A 2 year old brother had speech delay. The patient’s father had a history of mild congenital scoliosis, heart murmur and intellectual disability. The patient’s mother had a history of anemia, heart murmur and learning delays. There was no history of genetic conditions, recurrent pregnancy loss, or infant death. Chromosomal microarray analysis (CMA) demonstrated no clinically significant findings (ISCN: arr[hg19](1-22x2,(X,Y)x1). Trio exome sequencing with mitochondrial analysis, performed from a peripheral blood sample, demonstrated a paternally inherited likely pathogenic variant in HECW2 (NM_020760.1:c.2581 C>T) in exon 11. While this variant has not been previously published as benign or pathogenic, in silico analysis demonstrated a potential deleterious effect of the arginine to tryptophan substitution on structure and/or function. Mitochondrial analysis was negative/normal. We present the first documented case of HECW2-related disorder presenting with perinatal tachypnea. The patient’s hypotonia, feeding difficulties, dysmorphic features, pectus excavatum, vertebral malformations, scoliosis, and cardiac involvement correlate with previously described manifestations of HECW2-related disorder.

Abstract 6991: Impaired Systemic Oxygen Extraction Relates to Reduced Exercise Capacity in Post-COVID-19 Long Hauler Syndrome

Introduction: Following acute coronavirus 2019 (COVID-19) disease, at least 10% of patients report some form of residual limitation, most commonly dyspnea and fatigue. These COVID-19 “long haulers” experience symptoms that are largely unexplained by pulmonary function testing (PFT), echocardiogram and chest computed tomography (CT). Using invasive cardiopulmonary exercise testing, this pilot study characterized exercise limitation in 5 patients with persistent symptoms 1 year following mild COVID-19 illness. Methods: Following written informed consent, data were obtained in accordance with an IRB-approved protocol entailing placement of radial and pulmonary arterial catheters for pressure monitoring and blood sampling prior to and during maximum upright incremental exercise. Rest and exercise pulmonary hemodynamics, ventilation and gas exchange were recorded. Aerobic exercise capacity was estimated by peak O 2 consumption (VO 2 ). Results: All patients had normal biventricular and valvular function on resting echocardiogram, no evident parenchymal lung disease on CT, and normal PFTs. Resting mean pulmonary arterial pressure was ≤20 mmHg for all patients with pulmonary vascular resistance &lt;3 Woods units. At maximum exercise, all patients exhibited normal respiratory, cardiac output (% predicted), and total pulmonary vascular resistance responses, but demonstrated clearly depressed aerobic capacity (peak VO 2 &lt;80% predicted). Reduced peak VO 2 was associated with impaired systemic O 2 extraction as indicated by an arterial-venous O 2 content difference (adjusted for hemoglobin) of &lt;80% ( Figure 1 ). Conclusion: This case series provides preliminary evidence that reduced peak aerobic capacity among long haulers is primarily attributable to a peripheral (i.e., impaired systemic O 2 extraction), rather than central cardiopulmonary, limitation. These results suggest that systemic microcirculatory dysfunction contributes to exercise limitation.