Dilatation Of Right Ventricle Research Articles

3D-echocardiography for evaluation of the right ventricle in patients with repaired Tetralogy of Fallot: a comparison study with cardiac magnetic resonance

Abstract Background Patients with repaired Tetralogy of Fallot (ToF) need periodic instrumental assessments, due to complications they can meet during lifetime. Right ventricle (RV) dilation and dysfunction are some examples that explain why those patients regularly undergo Cardiac Magnetic Resonance (CMR), currently the gold standard method to detect these complications. Purpose 3D-echocardiography is an emerging tool to study RV, but there is little data supporting its use in congenital heart diseases. This study aimed at evaluating its accuracy in assessing RV dimensions and systolic function in ToF patients, in comparison to CMR. Methods 34 patients were prospectively enrolled after CMR performance. They all underwent standard 2D-echocardiography and Multi-Beat-ECG-triggered 3D Full-Volume acquisition. RV End Diastolic Volume (RV-EDV), End Systolic Volume and Ejection Fraction (RV-EF) were defined both in 3D-echocardiography and CMR. Results Post-hoc analysis of 3D images was performed through a vendor-independent software in 30 patients, resulting in a feasibility of 88%. A Bland-Altman analysis was performed, showing that 3D-echocardiography underestimates the RV-EDV/BSA of −27.39 mL/m2 on average (CI 95%: −29.46; −25.31, SD: 5.68 mL/m2), compared to CMR, as expected. However, when compared to normality reference, 3D-echocardiography identified RV dilatation with a significant correlation to CMR (V=0.66, p<0.001). Moreover, ROC curves showed that 3D-echo-RV-EDV/BSA is the echocardiographic measure that best correlates to CMR in detecting RV dilatation (AUC 1, CI 95%: 1.00; 1.00), followed by RVOT diameter in PLAX (AUC 0.89, CI 95%: 0.69; 0.99). Youden analysis suggested 77 mL/m2 (Se 95%, Sp 100%; J 0,95) as optimal limit to define RV dilatation in 3D-echocardiography. Regarding the RV-EF, the Bland-Altman analysis showed that 3D-echocardiography overestimates the RV-EF by 1,97% on average (CI 95%: 0.01; 3.95, SD: 5.43), compared to CMR. Secondly, accuracy of different echocardiographic parameters (both 2D and 3D) in detecting a RV systolic impairment was analyzed: ROC curves showed that RV-EF in 3D echocardiography is the measurement that best correlates to CMR in detecting RV dysfunction (AUC 0.92, CI 95%: 0.79–1.00), followed by Fractional Area Change (FAC) (AUC 0.78, CI 95%: 0.60; 0.96). Tricuspid Annular Plane Systolic Excursion (TAPSE) and tricuspid valve annular motion velocities in systole (S'-TDI), instead, showed very poor correlation. Conclusions 3D-echocardiography showed good agreement with CMR in defining RV dimensions and systolic function in ToF patients, even more than the bidimensional measurements cardiologists are used to. This could lead to a wider use of this tool in daily clinical practice, involving a reduction in the execution of the numerous CMR patients usually undergo. Moreover, it could be a valid instrument in patients with contraindication to CMR. Funding Acknowledgement Type of funding sources: None.

Different right ventricular maladaptation in heart failure patients with reduced or preserved ejection fraction: diagnostic and prognostic implication

Abstract Background The prognostic impact of right ventricle (RV) dysfunction and pulmonary hypertension (PH) in patients affected by chronic heart failure (HF) has been well described by several studies in both patients affected by HF with preserved ejection fraction (HFpEF) and HF with reduced ejection fraction (HFrEF). It has been been demonstrated that tricuspidal anular plane systolic excursion (TAPSE)/pulmonary artery systolic pressure (PASP) ratio, may provide additional prognostic information. However, the pathophysiological mechanisms leading to RV dysfunction may differ in HFpEF and HFrEF. Aims In this study we would like to evaluate: 1. Different RV adaptation in hospitalized HF patients with reduced or preserved EF 2. prognostic significance of an early echocardiographic assessment of RV structure comparing TAPSE/PASP vs s'/PASP in HFrEF and HFpEF. Methods We included 381 patients included in the study, 209 had HFrEF and 172 had HFpEF who were studied by echocardiography. S' wave and RV longitudinal function strain (RVLS) were obtained by apical four chamber view and optimal visualization of RV lateral free wall. RV diameter was measured at basal level below tricuspidal anular plane. Patients were followed for 6 months after discharge for the composite outcome of cardiovascular death and re-hospitalization. Results Patients with HFrEF demonstrated a larger RV end diastolic diameter (EDD) compared to HFpEF (43 [37–45] vs 39 [36–44] mm; p=0.009) and more reduced TAPSE (19 [16–21] vs 20 [17–22] mm; p=0.04). Whereas PASP values were similar in both groups. Conversely, s' wave and RVLS were much more reduced in HFpEF (9 [7–11] vs 12 [9–13] cm/sec; p=0.008; 16 [14–21] vs 20 [15–23]% p>0.05) than in HFrEF. TAPSE/PASP was significantly reduced in HFrEF (0.38 [0.29–0.42] vs 0.43 [0.35–0.48]; p=0.02). Conversely s'/PAPS was lower in HFpEF group (0.29 [0.24–0.33] vs 0.25 [0.21–0.31]; p=0.01). At univariate analysis several parameters were related to outcome: TAPSE≤14 mm, (HR 1.70 [1.14–2.52]; p=0.009), PASP≥40 mmHg (HR 1.51 [1.05–2.17]; p=0.02), RVEDD >38 mm (HR; 1.88 [1.36–2.61]; p<0.001), s wave<9 (HR1.88 [1.30–2.41] p<0.001),inferior cave vein diameter>21 mm (HR 1.90 [1.31–2.75]; p=0.001. Multivariable analysis confirmed prognostic role of TAPSE, RVEDD, IVC and s' wave. Therefore TAPSE /PAPS was associated with adverse event in HFrEF but not in HFpEF (HR 1,75 [1.41–2.92] in HFrEF, p=0.003; HR 1.02 [0.67–1.32] in HFpEF, p=0.55). Whereas, s/PAPS was associated with more increased risk in HFpEF (HR 1.88 [1.65–3.46] in HFpEF, p<0.001; HR 1.34 [1,08–4.32] in HFrEF, p=0.03). Conclusions Right ventricular dysfunction and maladaptation are associated with poor outcome in either HFrEF and HFpEF. Tissue excursion and longitudinal strain are much more impaired in HFpEF, whereas RV dilatation and reduced longitudinal function are closely related to HFrEF. Funding Acknowledgement Type of funding sources: None.

Right ventricular outflow tract Doppler flow analysis and pulmonary arterial coupling by transthoracic echocardiography in sepsis: a retrospective exploratory study

IntroductionRight ventricular (RV) and pulmonary vascular dysfunction appear to be common in sepsis. RV performance is frequently assessed in isolation, yet its close relationship to afterload means combined analysis with right ventricular outflow tract (RVOT) Doppler and RV–pulmonary arterial (RV–PA) coupling may be more informative than standard assessment techniques. Data on feasibility and utility of these parameters in sepsis are lacking and were explored in this study.MethodsThis is a retrospective study over a 3-year period of one-hundred and thirty-one patients admitted to ICU with sepsis who underwent transthoracic echocardiography (TTE) with RVOT pulsed wave Doppler. RVOT Doppler flow and RV–PA coupling was evaluated alongside standard measurements of RV systolic function and pulmonary pressures. RVOT Doppler analysis included assessment of pulmonary artery acceleration time (PAAT), velocity time integral and presence of notching. RV–PA coupling was assessed using tricuspid annular planar systolic excursion/pulmonary artery systolic pressure (TAPSE/PASP) ratio.ResultsPAAT was measurable in 106 (81%) patients, and TAPSE/PASP was measurable in 77 (73%). Seventy-three (69%) patients had a PAAT of ≤ 100 ms suggesting raised pulmonary vascular resistance (PVR) is common. RVOT flow notching occurred in 15 (14%) of patients. TRV was unable to be assessed in 24 (23%) patients where measurement of PAAT was possible. RV dysfunction (RVD) was present in 28 (26%), 26 (25%) and 36 (34%) patients if subjective assessment, TAPSE < 17 mm and RV dilatation definitions were used, respectively. There was a trend towards shorter PAAT with increasing severity of RVD. RV–PA uncoupling defined as a TAPSE/PASP < 0.31 mm/mmHg was present in 15 (19%) patients. As RV dilatation increased the RV–PA coupling ratio decreased independent of LV systolic function, whereas TAPSE appeared to be more susceptible to changes in LV systolic function.ConclusionRaised PVR and RV–PA uncoupling is seen in a significant proportion of patients with sepsis. Non-invasive assessment with TTE is feasible. The role of these parameters in assisting improved definitions of RVD, as well as their therapeutic and prognostic utility against standard parameters, deserves further investigation.

Therapeutic effects of nebulization-based delivery of anti-miR-146a in experimental pulmonary arterial hypertension

Abstract Pulmonary arterial hypertension (PAH), is a chronic disorder characterized by excessive pulmonary vascular remodelling, resulting in elevated pulmonary vascular resistance and right ventricle (RV) overload and failure. PAH remains incurable, and new therapeutic approaches are required. The microRNA-146a (miR-146a) promotes vascular smooth muscle cell proliferation and vascular neointimal hyperplasia, both important hallmarks of PAH. This study aimed to investigate the role of miR-146a in the pathophysiology of PAH and in the progression to RV hypertrophy and failure. Sprague Dawley rats received a subcutaneous injection of monocrotaline (MCT group) or vehicle (CTRL group) and, after fourteen days they were treated, by intratracheal nebulization, with an anti-miR-146a, forming four distinct groups: CTRL-treated; CTRL-untreated, MCT-treated, and MCT-untreated. Twenty-seven days after MCT injection, echocardiographic and invasive hemodynamic evaluations were performed in all animal groups. Also, wild-type (WT) and miR-146a knock-out (KO) (miR-146a−/−) mice were submitted to either 3 weeks of chronic hypoxia-induced PAH with weekly Sugen 5416 administration (SuHx). Compared to MCT-untreated rats, the MCT-treated rats showed decreased RV hypertrophy, (as measured by the Fulton index),decreased RV end-diastolic diameter/left ventricle end-diastolic diameter (RVEDD/LVEDD) ratio, and decreased in RV diastolic pressures. KO-SuHx group, when compared to WT-SuHx group, showed decreased RV hypertrophy (as measured by the Fulton index), and decreased RV systolic pressures and dilation, as well as lower RV end end-diastolic diameter (RVEDDi) and right atria area (RAAi). Our findings show that miR-146a pharmacological or genetic inhibition reduces RV remodelling and improves cardiac function. Thus, miR-146a represents a promising therapeutic target in PAH. Funding Acknowledgement Type of funding sources: Foundation. Main funding source(s): This research was supported by the Portuguese Foundation for Science and Technology (FCT).

Morphometric Characterization of an Ex Vivo Porcine Model of Functional Tricuspid Regurgitation

Emerging treatments for tricuspid valve (TV) regurgitation require realistic TV pathological models for preclinical testing. The aim of this work was to investigate structural features of fresh and defrosted porcine right-heart samples as models of mild and severe functional tricuspid regurgitation (FTR) condition in ex-vivo pulsatile flow platform. Ten fresh hearts were tested ex-vivo under steady and pulsatile flow in typical right-heart loading conditions. Hemodynamics and 3D echocardiographic imaging of TV and right ventricle (RV) were acquired. Hearts were then kept frozen for 14 days, defrosted, and tested again with the same protocol. Morphometric parameters of TV and RV were derived from 3D reconstructions based on echo data. Fresh samples showed a slightly dilated TV morphology, with coaptation gaps among the leaflets. Sample freezing induced worsening of TV insufficiency, with significant (p < 0.05) increases in annulus size (annulus area and perimeter 7.7–3.1% respectively) and dilation of RV (9.5%), which led to an increase in tenting volume (123.7%). These morphologic alterations reflected into a significant increment of regurgitation fraction (27%). Together, such results suggest that fresh porcine heart samples may be a reliable ex-vivo model of mild FTR condition, which can be enhanced through freezing/thawing treatment to model a severe pathological condition.

Right-to-left ventricle ratio determined by machine learning algorithms on CT pulmonary angiography images predicts prolonged ICU length of stay in operated chronic thromboembolic pulmonary hypertension.

Right-to-left ventricle diameter ratio (dRV/dLV) on CT pulmonary angiography (CTPA) is a predictor of outcomes in non-operated chronic thromboembolic pulmonary hypertension (CTEPH) patients. The purpose of this study is to evaluate the performance of a novel machine learning (ML) algorithm for dRV/dLV measurement in operated CTEPH patients and its association with post-operative outcomes. This retrospective study reviewed consecutive CTEPH patients who underwent pulmonary endarterectomy between 2013 and 2017. ML calculated dRV/dLV on pre-operative CTPA and compared with manual measures. Associations of dRV/dLV with patient characteristics and post-operative outcomes were evaluated including intensive care (ICU) and hospital length of stay (LOS) using multivariable linear regression analysis. Prolonged LOS was defined as greater than median. ML segmented the ventricles in 99/125 (79%) patients. The most common cause of failure was misidentification of the moderator band as the interventricular septum (7.9%). Mean dRV/dLV by ML was 1.4 ± 0.4 and strongly correlated with manual measures (r = 0.9-0.96 p < 0.0001). dRV/dLV was moderately correlated with measures of pulmonary hypertension on right heart catheterization and RV dilatation on echocardiogram (r = 0.5-0.6, p < 0.0001). dRV/dLV ≥ 1.2 was associated with proximal Jamieson type disease (p = 0.032), longer cardiopulmonary bypass (p = 0.037), aortic cross-clamp (p = 0.022) and circulatory arrest (p < 0.001) at surgery and dRV/dLV ≥ 1.6 with post-operative ECMO (p = 0.006). dRV/dLV was independently associated with prolonged ICU LOS (OR = 3.79, 95% CI 1.1-13.06, p = 0.035). dRV/dLV was associated with CTEPH severity and independently associated with prolonged ICU LOS. This CT parameter may therefore assist in perioperative planning. Further refinement of the ML algorithm or CTPA technique is required to avoid errors in ventricular segmentation. Automated right-to-left ventricle ratio measurement by machine learning is feasible and is independently associated with outcome after pulmonary endarterectomy.

A novel echocardiographic right ventricular dysfunction score can identify hemodynamic severity profiles in left ventricular dysfunction

PurposeRecognition of congestion and hypoperfusion in patients with chronic left ventricular dysfunction (LVD) has therapeutic and prognostic implications. In the present study we hypothesized that a multiparameter echocardiographic grading of right ventricular dysfunction (RVD) can facilitate the characterization of hemodynamic profiles.MethodsConsecutive patients (n = 105, age 53 ± 14 years, males 77%, LV ejection fraction 28 ± 11%) referred for heart transplant or heart failure work-up, with catheterization and echocardiography within 48 h, were reviewed retrospectively. Three hemodynamic profiles were defined: compensated LVD (cLVD, normal pulmonary capillary wedge pressure (PCWP < 15 mmHg) and normal mixed venous saturation (SvO2 ≥ 60%)); decompensated LVD (dLVD, with increased PCWP) and LV failure (LVF, increased PCWP and reduced SvO2). We established a 5-point RVD score including pulmonary hypertension, reduced tricuspid annular plane systolic excursion, RV dilatation, ≥ moderate tricuspid regurgitation and increased right atrial pressure.ResultsThe RVD score [median (IQR 25%;75%)] showed significant in-between the three groups differences with 1 (0;1), 1 (0.5;2) and 3.0 (2;3.5) in patients with cLVD, dLVD and LVF, respectively. The finding of RVD score ≥ 2 or ≥ 4 increased the likelihood of decompensation or LVF 5.2-fold and 6.7-fold, respectively. On the contrary, RVD score < 1 and < 2 reduced the likelihood 11.1-fold and 25-fold, respectively. The RVD score was more helpful than standard echocardiography regarding identification of hemodynamic profiles.ConclusionsIn this proof of concept study an echocardiographic RVD score identified different hemodynamic severity profiles in patients with chronic LVD and reduced ejection fraction. Further studies are needed to validate its general applicability.Graphical abstract

Right heart strain assessment on CTPA following acute pulmonary embolism: Interobserver variability between expert radiologists and physicians

BackgroundAccuracy of right heart strain (RHS) measured on computed tomography pulmonary angiogram (CTPA) scans by non-radiologists is unknown. We assessed inter-observer variability of four RHS features and determined the accuracy of measurements by respiratory physicians. Method1560 consecutive patients with acute PE were identified, and those who had a CTPA and an echocardiogram within 24-h included. CTPAs were independently scored prospectively by two radiologists, two thoracic physicians and a specialist registrar. Inter-observer variability was assessed, and diagnostic accuracy compared to echocardiography. Results182 patients (median age 62.8 years, IQR 49.8–71.5) with acute PE (7.7% high-risk, 40.7% intermediate high-risk, 31.3% intermediate low-risk and 20.3% low-risk) were included. Right ventricle to left ventricle diameter ratio (RV:LV) measurement had low inter-observer variability among the radiologists and non-radiologists with interclass correlation coefficient (ICC) of 0.95 (95%CI 0.92–0.97) and 0.96 (95%CI 0.94–0.97) respectively. RV:LV ratio had high diagnostic accuracy compared to RV dilatation on echocardiography (AUC 0.89, 95%CI 0.84–0.94 for radiologists and AUC 0.84, 95%CI 0.77–0.90 for non-radiologists). Main pulmonary artery to ascending aorta diameter ratio (MPA:Ao) measurement also had excellent agreement amongst the radiologists and non-radiologists (ICC 0.93 (95%CI 0.88–0.96) and 0.92 (95%CI 0.81–0.96) respectively). Significant variability was seen in the assessment of subjective features of RHS (leftward bowing of interventricular septum and contrast reflux into inferior vena cava) amongst the non-radiologists. ConclusionRV:LV and MPA:Ao diameter ratios on CTPA measured by non-radiologists have low inter-observer variability and good agreement with radiologists, and can be reliably used where an expert report is unavailable.

Pre- and Postprocedure Imaging of Transcatheter Pulmonary Valve Implantation.

Transcatheter pulmonary valve replacement (TPVR) is a minimally invasive procedure for treatment of right ventricular outflow tract (RVOT) dysfunction in surgically repaired congenital heart diseases. TPVR is performed in these patients to avoid the high risk and complexity of repeat surgeries. Several TPVR devices are now available to be placed in the right ventricle (RV) to pulmonary artery (PA) conduit, native RVOT, or surgical bioprosthetic valves. Imaging is used before TPVR to determine patient eligibility and optimal timing, which is critical to avoid irreversible RV dilatation and failure. Imaging is also required for evaluation of contraindications, particularly proximity of the RVOT to the left main coronary artery and its branches. Cross-sectional imaging provides details of the complex anatomy in which the TPVR device will be positioned and measurements of the RVOT, RV-PA conduit, or PA. Echocardiography is the first-line imaging modality for evaluation of the RVOT or conduit to determine the need for intervention, although its utility is limited by the complex RVOT morphology and altered anatomy after surgery. CT and MRI provide complementary information for TPVR, including patient eligibility, assessment of contraindications, and key measurements of the RVOT and PA, which are necessary for procedure planning. TPVR, performed using a cardiac catheterization procedure, includes a sizing step in which a balloon is expanded in the RVOT, which also allows assessment of the risk for extrinsic coronary artery compression. Follow-up imaging with CT and MRI is used for evaluation of postprocedure remodeling and valve function and to monitor complications. ©RSNA, 2022 Online supplemental material is available for this article.

Factors associated with discontinuation of pulmonary vasodilator therapy in children with bronchopulmonary dysplasia-associated pulmonary hypertension.

To evaluate factors associated with discontinuation of pulmonary vasodilator therapy in bronchopulmonary dysplasia-related pulmonary hypertension (BPD-PH). Retrospective study of neonatal, echocardiographic, and cardiac catheterization data in 121 infants with BPD-PH discharged on pulmonary vasodilator therapy from 2009-2020 and followed into childhood. After median 4.4 years, medications were discontinued in 58%. Those in whom medications were discontinued had fewer days of invasive support, less severe BPD, lower incidence of PDA closure or cardiac catheterization, and higher incidence of fundoplication or tracheostomy decannulation (p < 0.05). On multivariable analysis, likelihood of medication discontinuation was lower with longer period of invasive respiratory support [HR 0.95 (CI:0.91-0.99), p = 0.01] and worse RV dilation on pre-discharge echocardiogram [HR 0.13 (CI:0.03-0.70), p = 0.017]. In those with tracheostomy, likelihood of medication discontinuation was higher with decannulation [HR 10.78 (CI:1.98-58.59), p < 0.001]. In BPD-PH, childhood discontinuation of pulmonary vasodilator therapy is associated with markers of disease severity.

Pulmonary artery obstruction index, pulmonary artery diameter and right ventricle strain as prognostic CT findings in patient with acute pulmonary embolism

ObjectiveThis study was designed to determine predictors of pulmonary hypertension and signs of right heart dysfunction caused by pulmonary embolism (PE) that may lead to early detection of high-risk patients. So the predictive value of pulmonary artery obstruction index (PAOI), measured by pulmonary CT angiography (PCTA) in the acute setting, in predicting the patients susceptible to PE cardiac complications was evaluated. Also two other PCTA indices, pulmonary artery diameter (PAD), and right ventricle (RV) strain, in these patients were investigated and their predictive value for cardiac complications on follow up echocardiography were demonstrated. Materials and methodsIn the study 120 patients with a definite diagnosis of PE were included. The PAOI, PAD and RV strain were measured using PCTA at the time of the initial diagnosis. Transthoracic echocardiography was done 6 months after the diagnosis of PE and RV echocardiographic indices were measured. Pearson correlation was used to investigate correlation between PAOI, PAD, RV strain and signs of right heart dysfunction. ResultsPAOI was strongly correlated with systolic pulmonary artery pressure (SPAP) (r=0.83), RV systolic pressure (r=0.78) and RV wall thickness (r=0.61) in long-term follow up echocardiography. A higher rate of RV dysfunction and RV dilation was detected among the patients with higher PAOI (P<0.001). PAOI≥18 was strongly predictive for development of RV dysfunction. Also developments of pulmonary hypertension, RV systolic hypertension, RV dilation, RV dysfunction, and RV hypertrophy were significantly more common among patients with higher PAD and RV strain (P<0.001). ConclusionsPAOI, PAD and RV strain are sensitive and specific PCTA indices that can predict the development of long-term complications such as pulmonary hypertension and right heart dysfunction, at the time of initial PE diagnosis.

THERAPEUTIC EFFECTS OF NEBULIZATION- BASED DELIVERY OF ANTI-MIR-146A IN EXPERIMENTAL PULMONARY ARTERIAL HYPERTENSION

Objective: Pulmonary arterial hypertension (PAH), is a chronic disorder characterized by excessive pulmonary vascular remodelling, resulting in elevated pulmonary vascular resistance and right ventricle (RV) overload and failure. PAH remains incurable, and new therapeutic approaches are required. The microRNA-146a (miR-146a) promotes vascular smooth muscle cell proliferation and vascular neointimal hyperplasia, both important hallmarks of PAH. This study aimed to investigate the role of miR-146a in the pathophysiology of PAH and in the progression to RV hypertrophy and failure. Design and method: Sprague Dawley rats received a subcutaneous injection of monocrotaline (MCT group) or vehicle (CTRL group) and, after fourteen days they were treated, by intratracheal nebulization, with an anti-miR-146a, forming four distinct groups: CTRL-treated; CTRL-untreated, MCT-treated, and MCT-untreated. Twenty-seven days after MCT injection, echocardiographic and invasive hemodynamic evaluations were performed in all animal groups. Also, wild-type (WT) and miR-146a knock-out (KO) (miR-146a-/-) mice were submitted to either 3 weeks of chronic hypoxia-induced PAH with weekly Sugen 5416 administration (SuHx). Results: Compared to MCT-untreated rats, the MCT-treated rats showed decreased RV hypertrophy, (as measured by the Fulton index), decreased RV end-diastolic diameter/left ventricle end-diastolic diameter (RVEDD/LVEDD) ratio, and decreased in RV diastolic pressures. KO-SuHx group, when compared to WT-SuHx group, showed decreased RV hypertrophy (as measured by the Fulton index), and decreased RV systolic pressures and dilation, as well as lower RV end end-diastolic diameter (RVEDDi) and right atria area (RAAi). Conclusions: Our findings show that miR-146a pharmacological or genetic inhibition reduces RV remodelling and improves cardiac function. Thus, miR-146a represents a promising therapeutic target in PAH.

AN INTERESTING CASE OF CARDIAC ARREST DURING THE CREATION OF AV FISTULA

TYPE: Case Report TOPIC: Cardiovascular Disease INTRODUCTION: We present an intersting case of cardiac arrest due to hemodynamic compromise occurring soon after AV fistula creation. CASE PRESENTATION: 45-year-old woman with medical history of ESRD on hemodialysis and pulmonary hypertension presented for left-arm AV fistula creation. Initial parts of the procedure went uneventful. However, towards the end of procedure, 10 minutes after unclamping of the graft, patient became hypotensive and suffered from cardiac arrest secondary to pulseless ventricular tachycardia progressing to torsades. Patient received CPR and multiple defibrillator shocks, epinephrine, IV magnesium sulfate and amiodarone boluses. Blood gas showed pH of 7.05 and lactate 6.5 mmol/L. Potassium, magnesium and phosphate levels were normal. She was started on epinephrine drip for hemodynamic support and heparin drip due to concern of PE. STAT TTE showed severe LVH with LVEF of 55 to 60%, moderate pulmonary hypertension, normal RV size and function. CTA of chest did not show any evidence of pulmonary embolism therefore heparin was stopped. Patient was transferred to ICU where she remained stable and had a full neurologic recovery. DISCUSSION: AV fistula creation in patients with pre-existing pulmonary hypertension and RV dysfunction could result in increased venous return and RV preload leading to acute RV dilatation. This could cause septal shift towards the left resulting in decreased LV preload, leading to decreased cardiac output, potentially resulting in hypotension. Decreased coronary and systemic perfusion could also result in myocardial ischemia and RV failure leading to arrhythmias and death. CONCLUSIONS: Physicians should be aware of this potentially fatal acute complication of AV fistula creation. DISCLOSURE: Nothing to declare. KEYWORD: Cardiac Arrest, AV Fistula, hemodynamic effects, dialysis access, high output cardiac failure

European Neuroendocrine Tumor Society (ENETS) 2022 Guidance Paper for Carcinoid Syndrome and Carcinoid Heart Disease

European Neuroendocrine Tumor Society (<scp>ENETS</scp>) 2022 Guidance Paper for Carcinoid Syndrome and Carcinoid Heart Disease

Computational modeling identifies the cellular electromechanical effects of disrupted intracellular calcium handling in arrhythmogenic cardiomyopathy patients

Abstract Funding Acknowledgements Type of funding sources: Public grant(s) – National budget only. Main funding source(s): NWO - ZonMw (VIDI grant 016.176.340 to JL) Dutch Heart Foundation (ERA-CVD JTC2018 grant 2018T094; Dr. Dekker Program grant 2015T082 to JL) The Netherlands Cardio Vascular Research Initiative (CVON): the Dutch Heart Foundation, Dutch Federation of University Medical Center, the Netherlands Organization for Health Research and Development and the Royal Netherlands Academy of Sciences (CVON-eDETECT 2015-12 and CVON-PREDICT2 2018-30 to TvV). Background Patients with arrhythmogenic cardiomyopathy (ACM), an inherited progressive cardiac disease, mostly remain asymptomatic until the occurrence of life-threatening arrhythmias. Previous research identified disturbed calcium handling as a potential disease-initiating mechanism [1], but how this translates to arrhythmogenesis and cardiac mechanical dysfunction remains unknown. Purpose To characterize disturbed molecular regulators of intracellular calcium (Ca2+) handling in patients with ACM and predict their effects on action potential (AP), calcium transient (CaT) and tension development in both left and right ventricles (LV, RV) using a computer model of cellular electromechanics. Methods We performed gene expression (qPCR) and protein level (Western blot) analysis using LV and RV tissue samples obtained from 5 ACM patients who underwent heart transplant and 5 controls with no history of cardiac disease. Changes in protein levels were implemented in our recent human electromechanical cardiomyocyte computer model [2]. CaT, AP and tension traces were simulated and compared to control. Clinical data (age, sex, genetics, ECG, echocardiography) were related to the simulation outcome. Results Measured protein levels varied significantly between the 5 patients and between individual LV and RV samples. Exemplary results for one ACM patient are shown in the figure below. In the LV, AP duration was shorter than control (221ms vs. 255ms), CaT peak was increased (0.52µM vs. 0.39µM) but CaT amplitude was reduced due to increased diastolic Ca2+ (0.26µM vs. 0.060µM). Relaxation was also impaired, as shown by a longer CaT and tension duration (965ms vs. 640ms), and an increased diastolic tension (10mN vs. 4.8mN). In the RV, AP duration was shortened, and CaT and tension peak were lower than in the LV (0.37µM and 13.6mN). Diastolic levels were elevated compared to control, and CaT and tension development were prolonged. This can be related to the measured Ca2+ changes: in the LV, a lower activity of the sodium-calcium exchanger (NCX) (22% of control) and SERCA pump (52%) combined with an increased ryanodine receptor (RyR) activity (96%) may impair the extrusion of Ca2+, leading to accumulation of Ca2+ and increased diastolic Ca2+ levels. In the RV, milder changes in NCX (48% of control) and RyR (11%) may explain the larger Ca2+ extrusion, leading to lower CaT peak and diastolic levels. The patient showed a normal LV size, a severely dilated RV, as well as a poor LV fractional shortening suggesting increased ventricular stiffness, in line with the potential impaired relaxation shown by the simulations. Conclusion By integrating protein level data from ACM patients into a computational model of cellular electromechanics, we quantified the electromechanical effects of patient-specific Ca2+ handling changes. Future whole-heart extensions of this work have the potential to identify and understand proarrhythmic mechanisms in ACM patients.

P392 A MULTIMODALITY IMAGING DIAGNOSIS OF A CHALLENGING CASE OF CONCOMITANT GROUP 1 PULMONARY HYPERTENSION AND PARADOXICALLY LOW–FLOW, LOW–GRADIENT AORTIC STENOSIS

Abstract A 76 year old woman was admitted to our hospital for self–limiting dyspnoea (NYHA class III) in oxygen dependence and frequent lipothymia following Valsalva manoeuvres. She was previously admitted to a Spoke Centre for heart failure (HF) with preserved ejection fraction (EF) and a new diagnosis of “pre–capillary pulmonary hypertension (PH)”. Despite a diagnosis of PH of unclear aetiology, she was started on macitentan without being reassessed for functional capacity due to Covid emergency; because of worsening symptoms, she was admitted to our Hub Centre. Resting ECG showed right axis deviation, right ventricle (RV) hypertrophy, first–degree atrioventricular block and right bundle branch block. Transthoracic echocardiography (TTE) showed reduced left ventricular (LV) volume with preserved EF (diastolic volume= 37 ml, EF = 88%), severe right atrial and RV dilation with flattening of the interventricular septum, estimated pulmonary artery systolic pressure (PASP) of 124 mmHg, and moderate calcific aortic stenosis (peak aortic velocity 3.3 m/s, mean gradient 25 mmHg, valve area 1.1 cm2). Right and left heart catheterization showed severe pre–capillary PH (mean pulmonary pressure 60 mmHg, mean wedge 11 mmHg, pulmonary vascular resistance 14.41 WU), a severe aortic valve stenosis (aortic valve area 0.68 cmq and peak–to–peak gradient 25 mmHg, slight reduction of cardiac index 2.04 l/min/mq) and no significant coronary artery disease. The degree of aortic stenosis was considered as moderate–severe by integrating data of transesophageal echocardiography (planimetric area 1cm2) and assessment of calcium score (1615 Agatson units). Pneumological causes, chronic thromboembolic PH, rheumatologic diseases, HIV infection, paraneoplastic origin and veno–occlusive disease were all ruled out as potential PH causes and a diagnosis of Idiopathic pulmonary arterial hypertension (IPAH) was finally made. The Heart Team established the best therapeutic option was a transcatheter aortic valve replacement (TAVI) allowing better haemodynamic tolerability of PH therapy. The patient underwent TAVI and was started on PH therapy; a complete atrio–ventricular block developed after the procedure, requiring permanent pacemaker (PM) implantation. Unfortunately, few days later, the patient died following pacemaker’s lead dislocation. Conclusion PH has a diverse aetiology, and prognosis is generally poor, especially in patients with severe comorbidities.

C63 PHENOTYPE – GENOTYPE RELATIONSHIP IN ARRHYTHMOGENIC CARDIOMYOPATHY

Abstract Background Arrhythmogenic cardiomyopathy (ACM) is a primary disease of the myocardium with arrhythmic manifestations and fibro–fatty replacement either of the right (RV) or the left ventricle (LV) at the cardiac magnetic resonance (CMR). Over the last decade, different mutations in cardiac genes associated with heterogeneous phenotypes have been identified. Aim To investigate the genotype–phenotype relationships in ACM patients. Firstly, the phenotypic expression was defined in definite mutation carriers. Secondly, the prognostic significance of mutations was assessed across different phenotypes. Methods The study population included 281 patients with suspected ACM, based on family history, clinical and electrocardiographic evaluation, echocardiographic and CMR findings (Fig.1), studied at our Institution since 2012. All patients underwent genetic evaluation using Sanger sequencing and NGS of mutations in desmosomal (desmoplakin [DSP], plakophilin–2[PKP2], plakoglobin[JUP], desmoglein–2 [DSG2], desmocollin–2 [DSC2]) or non desmosomal genes. The composite endpoint included cardiac death, sustained and non–sustained ventricular tachycardia (VT), ventricular fibrillation (VF), appropriate defibrillator shock/antitachycardia pacing (ATP). Results The genetic test was positive in 113 patients (40%), 82 (73%) for desmosomal genes (41 DSP, 15 DSG2, 15 PKP2, 5 JUP, 6 DSC2), and 31 (27%) for non–desmosomal genes (4 titin, 2 TMEM 43, 2 lamin A/C, 23 others). Gene–positive compared to gene–negative (n = 168, 60%) patients showed a higher prevalence of LV ejection fraction (EF)&amp;lt;50% (14%vs.6%, p&amp;lt;0.011), LV and RV LGE (62%vs.46%, p &amp;lt; 0.001, 20%vs.12%, p&amp;lt;0.02), RV dilatation (27%vs.17%, p&amp;lt;0.041) (Table 1). DSG2 mutations were associated mainly to biventricular (7/15,46%) or RV involvement (4/15,26%), while DSP mutations to LV involvement (24/41,58%). During a median 36–month follow–up (IQ.range 12–56), 55 patients (19%) experienced the composite endpoint (35 non–sustained VT; 11 sustained VT – 3 ATP, 1 defibrillator–shock–; 9 VF, all treated by defibrillator–shock). At Kaplan–Meier analysis, DSP mutations were associated with the worst prognosis (Fig. 3). Conclusion Diverse genotypes were differently associated with LV dysfunction/LGE, RV dilatation/LGE. DSP mutations were associated with higher arrhythmic risk. Genetic screening may result in a better risk stratification, useful for clinical decision–making.

Increased RV:LV ratio on chest CT-angiogram in COVID-19 is a marker of adverse outcomes

BackgroundRight ventricular (RV) dilation has been used to predict adverse outcomes in acute pulmonary conditions. It has been used to categorize the severity of novel coronavirus infection (COVID-19) infection. Our study aimed to use chest CT-angiogram (CTA) to assess if increased RV dilation, quantified as an increased RV:LV (left ventricle) ratio, is associated with adverse outcomes in the COVID-19 infection, and if it occurs out of proportion to lung parenchymal disease.ResultsWe reviewed clinical, laboratory, and chest CTA findings in COVID-19 patients (n = 100), and two control groups: normal subjects (n = 10) and subjects with organizing pneumonia (n = 10). On a chest CTA, we measured basal dimensions of the RV and LV in a focused 4-chamber view, and dimensions of pulmonary artery (PA) and aorta (AO) at the PA bifurcation level. Among the COVID-19 cohort, a higher RV:LV ratio was correlated with adverse outcomes, defined as ICU admission, intubation, or death. In patients with adverse outcomes, the RV:LV ratio was 1.06 ± 0.10, versus 0.95 ± 0.15 in patients without adverse outcomes. Among the adverse outcomes group, compared to the control subjects with organizing pneumonia, the lung parenchymal damage was lower (22.6 ± 9.0 vs. 32.7 ± 6.6), yet the RV:LV ratio was higher (1.06 ± 0.14 vs. 0.89 ± 0.07). In ROC analysis, RV:LV ratio had an AUC = 0.707 with an optimal cutoff of RV:LV ≥ 1.1 as a predictor of adverse outcomes. In a validation cohort (n = 25), an RV:LV ≥ 1.1 as a cutoff predicted adverse outcomes with an odds ratio of 76:1.ConclusionsIn COVID-19 patients, RV:LV ratio ≥ 1.1 on CTA chest is correlated with adverse outcomes. RV dilation in COVID-19 is out of proportion to parenchymal lung damage, pointing toward a vascular and/or thrombotic injury in the lungs.

Role of cardiomyocytes in right ventricle viscoelasticity with pulmonary hypertension development

BackgroundThe myocardium is viscoelastic, which means there exists elastic and viscous resistant forces during cardiac motion. It has been shown that cardiomyocyte (CM) or muscle fiber has significant viscoelasticity, and microtubule depolymerization via colchicine treatment reduces the CM’s viscoelasticity. However, most prior study is focused on the left ventricle, and the role of CM in right ventricle (RV) viscoelasticity in healthy and pulmonary hypertensive (PH) states is poorly understood. Our goal is to evaluate the contribution of CM to RV viscoelasticity in healthy and PH rats. We hypothesize that CM contributes to both healthy and PH RV viscoelasticity.MethodsAll procedures were approved by Colorado State University IACUC. 6‐week‐old male rats were treated with 3‐week monocrotaline (MCT) (60 mg/kg) to induce PH, and intact healthy rats served as control. RV function was quantified by echocardiography and in vivo pressure‐volume (PV) measurements. After euthanasia, RV free wall underwent equibiaxial stress relaxation in a relaxant bath to obtain passive, biaxial viscoelasticity pre and post colchicine treatment (0.3mM). The tissue was stretched at 20% of strain and with physiological ramp speed (5Hz). Relaxation modulus and normalized stress at 0.01 s were used to quantify elasticity and viscosity. Student t test was performed.ResultsIn vivo RV function measurements showed the development of PH and RV failure in MCT rats (Table 1). Marked RV dilation and decreased fractional shortening confirmed the RV failure establishment. PV loop data with fewer samples (n=3) also implies declines in cardiac output, contractility (Ees) and ventricular‐vascular coupling (Ees/Ea). At the baseline, PH development led to increased viscoelasticity in the RV (Fig. 1). Mechanical data before and after colchicine treatment showed reduced elasticity in both healthy and MCT RVs (Fig. 1A&amp;B). The percentage reduction in elasticity was similar between groups, indicating a similar contribution of CM to RV elasticity. Unexpectedly, we did not observe significant change in viscosity after colchicine treatment in both groups (Fig. 1C&amp;D). Moreover, the control RVs were isotropic, whereas the MCT RVs showed marked anisotropy in elasticity (Fig. 1B).ConclusionOur results demonstrated similar impact of CM on RV viscoelasticity before and after PH development, despite the CM hypertrophy. Colchicine reduced elasticity in healthy and MCT RVs, but minimally changed RV viscosity. These findings will deepen the understanding of biomechanical mechanism of RV failure associated with viscoelastic changes.

PO-704-07 HIGH INCIDENCE OF ARRHYTHMOGENIC SUBSTRATE AND VENTRICULAR TACHYCARDIA INDUCIBILITY IN REPAIRED TETRALOGY OF FALLOT PATIENTS UNDERGOING PRE-PULMONARY VALVE REPLACEMENT EP STUDY

Sudden cardiac death due to ventricular arrythmias (VAs) remains a concern for patients with repaired Tetralogy of Fallot (rToF). The presence of slowly conducting anatomic isthmuses (SCAI) have been shown predict VA induction during invasive EP study (EPS). Pulmonary valve replacement (PVR) is often needed in rToF and may lead to surgical exclusion of critical isthmuses by prosthetic material. Describe incidence and predictors of SCAIs and VT inducibility in rToF patients prior to PVR. All patients (2019-2021) undergoing PVR with rToF were referred for EPS, electroanatomic mapping and programmed stimulation. SCAI were defined as a conduction velocity across defined anatomic isthmuses of <0.5m/s. Ablation was recommended at all SCAIs, regardless of inducibility. Univariate analysis was performed to identify predictors of the presence of SCAI or VT inducibility at EPS. Twenty-four patients underwent EPS with mapping. SCAI was identified in 54% of patients (PV to VSD isthmus in all, VSD to tricuspid annulus in 3, and RV to PA in one). VT was inducible in 54% of these, and 12/13 patients with SCAI were ablated. No VT was seen in follow-up of 16 +/- 19 months. Age at EPS (p=0.037), moderate-severe RV dilation (p=0.36), and absence of prior PVR (p=0.035) were predictive of SCAI presence. SCAI are seen in over one half of rTOF patients undergoing pre-PVR EPS. Given the high incidence of arrhythmogenic substrate and inducible VT without exclusionary clinical predictors in this cohort, all rTOF patients undergoing PVR should undergo pre-PVR EPS for risk stratification.