Dilatation Of Right Ventricle Research Articles

Predictive value of Cardiac Magnetic Resonance: new and old parameters in the natural history of repaired Tetralogy of Fallot

BackgroundPatients with repaired Tetralogy of Fallot (rTOF) often develop pulmonary regurgitation (PR) and right ventricle (RV) dysfunction, experiencing increased mortality and morbidity rates in adulthood. Pulmonary valve replacement (PVR) timing to address PR is controversial. Cardiac Magnetic Resonance (CMR) is the gold standard for morpho-functional evaluation of complex cardiopathies. This study aims to identify CMR parameters predictive of adverse outcomes to help defining the best therapeutic management of rTOF patients.Methods130 rTOF patients who underwent CMR (2006–2019) were enrolled in this retrospective single-center study. CMR, clinical, ECG and exercise data were analyzed. Univariate and multivariate analyses identified clinical and CMR parameters predictive of adverse outcomes both individually (e.g., death, arrhythmias, heart failure (HF), pharmacological therapy, QRS ≥ 160ms) and as composite outcome.ResultsUnivariate analysis confirmed RV volumes and RV ejection fraction corrected for PR as adverse outcome predictors and identified interesting correlations: pulmonary artery bifurcation geometry and abnormal interventricular septum (IVS) motion with arrhythmias (p < .001; p = .037), HF (p = .049; p = .005), composite outcome (p = .039; p = .009); right atrium (RA) dimensions with the composite outcome and the outcomes individually (p < .001). The best predictive models by multivariate analysis included sex (male), RV and RA dilation for QRS ≥ 160ms, time form repair to CMR, age at TOF repair and IVS fibrosis for pharmacological therapy.ConclusionsBesides RV volumes, new adverse prognostic factors could guide rTOF therapeutic management: pulmonary arteries morphology, abnormal IVS motion, RV dysfunction, RA dilation. Perspective multicentric evaluation is needed to specify their effective role.

Kiosk 4R-FA-01 - CMR Derived RVEDV/LVEDV Ratio Improves Detection of Severe RV Dilation in Pre-capillary Pulmonary HTN Compared to Rvedvi

Kiosk 4R-FA-01 - CMR Derived RVEDV/LVEDV Ratio Improves Detection of Severe RV Dilation in Pre-capillary Pulmonary HTN Compared to Rvedvi

A Dynamic Sheep Model to Induce Pulmonary Hypertension and Right Ventricular Failure.

Decompensated right ventricular failure (RVF) in pulmonary hypertension (PH) is fatal, with limited medical treatment options. Developing and testing novel therapeutics for PH requires a clinically relevant large animal model of increased pulmonary vascular resistance and RVF. This manuscript describes the method to induce an ovine PH-RVF model that utilizes left pulmonary artery (LPA) ligation, progressive main pulmonary artery (MPA) banding, and insertion of an RV pressure line for monitoring. The PA cuff and RV pressure tubing are connected to subcutaneous access ports. This model of PH-RVF is a versatile platform to control not only the disease severity, but also the RV's phenotypic response. Subjects undergo progressive PA band adjustments twice per week for approximately 9weeks with sequential measures of RV pressure, PA cuff pressures, and mixed venous blood gas (SvO2). Subjects can further be exercised on a livestock treadmill while hemodynamic parameters are captured. At the initiation and endpoint of this model, ventricular function and dimensions are assessed using echocardiography. In this model, RV mean and systolic pressure increased to 28±5 and 57±7mmHg at week 1, and further to 44±7 and 93±18mmHg by week 9, respectively. Echocardiography demonstrates characteristic findings of PH-RVF, notably RV dilation, increased wall thickness, and septal bowing. The rate of PA banding has a significant impact on SvO2 and thus the model can be titrated to elicit varying RV phenotypes. When the PA cuff is tightened rapidly, it can lead to a precipitous decline in SvO2, leading to RV decompensation, whereas a slower, more paced strategy leads to an adaptive RV stress-load response that maintains physiologic SvO2. A faster rate of PA banding will also lead to more severe liver fibrosis. The addition of controlled exercise provides a useful platform for assessing the effects of physical exertion in a PH-RVF model. This chronic PH-RVF model provides a valuable tool for studying molecular mechanisms, developing diagnostic biomarkers, and evaluating mechanical circulatory support systems.

Obesity and heart failure with preserved ejection fraction.

Aim: To perform an overall assessment of heart failure with preserved ejection fraction (HFpEF) adults with central obesity. Materials and Methods: We enrolled HFpEF patients with central obesity (n =73, mean age 52.4 ± 6.3 years) and without obesity (n =70, mean age 51.9 ± 7.1 years) and compared with an age-matched healthy subjects who had not suffered from HF (n = 69, mean age 52.3 ± 7.5 years). Physical examination, routine laboratory tests such as fasting blood glucose, fasting insulin, insulin resistance (HOMA) index, serum lipids, haemoglobin, creatinine, ALT, AST, uric acide, hs CRP, TSH, N-terminal proB-type natriuretic peptide (NT-proBNP) and standard transthoracic echocardiogram (2D and Doppler) examinations were performed and assessed. Results: The average values of diastolic blood pressure (DBP), glucose and lipid profiles, uric acide, hs CRP were found to be significantly higher among obese patients with HFpEF than non-obese. Despite more severe symptoms and signs of HF, obese patients with HFpEF had lower NT-proBNP values than non-obese patients with HFpEF (129±36.8 pg/ml, 134±32.5 pg/ml vs 131±30.4 pg/ml, 139±33.8 pg/ml respectively; p < 0.05). However, it was found that patients with high central (visceral) adiposity have more pronounced obesity-related LV diastolic dysfunction, lower E/e' ratio, lower mitral annular lateral e' velocity, an increased LV diastolic dimension and LV mass index. Compared with non-obese HFpEF and control subjects, obese patients displayed greater right ventricular dilatation (base, 35±3.13 mm, 36±4.7 mm vs 33±2.8 mm, 34±3.2 mm and 29±5.3 mm, 30±3.9 mm; length, 74±5 mm, 76±8 mm vs 67±4 mm, 69±6 mm and 60±3 mm, 61±5 mm respectively; p < 0.05), more right ventricular dysfunction (TAPSE 16±2 mm, 15±3 mm vs 17±2 mm, 17±1 mm and 19±2 mm, 20±3 mm respectively; p < 0.05). Conclusions: Obese patients with HFpEF have higher diastolic BP, atherogenic dyslipidemia, insulin resistance index values and greater systemic inflammatory biomarkers, despite lower NT-proBNP values, which increase the risk of cardiovascular events in future. Echocardiography examination revealed not only significant LV diastolic dysfunction, but also displayed greater RV dilatation and dysfunction.

Diagnostic Accuracy of Cardiac Point-of-Care Ultrasound in a Tertiary Medical Intensive Care Unit

Objective: Critical care echocardiography (CCE) is a useful tool for managing critically ill patients in intensive care. However, concerns exist regarding the accuracy of CCE examinations because of operator dependence. We sought to evaluate the accuracy of CCE examinations compared with cardiology-performed transthoracic echocardiogram (TTE). Design, Setting, and Subjects: We retrospectively reviewed charts of patients in a medical ICU in a large academic medical center in the United States. We compared CCE examinations performed by a fellow and reviewed by a staff physician between May 5, 2020, and December 31, 2021, to TTE obtained within 24 hours of the CCE examination. Intervention, Measurements, and Main Results: We developed a standardized process for documentation of all CCE examinations performed in the medical ICU. We assessed agreement (kappa statistic), sensitivity and specificity of CCE examination compared with TTE. Features included left ventricle (LV) systolic function, right ventricle (RV) size, RV systolic function, pericardial effusion, mitral insufficiency, tricuspid insufficiency, and aortic insufficiency. The study analyzed 504 pairs of CCE and TTE examinations. Kappa statistics for detecting LV and RV systolic dysfunction, pericardial effusion, and RV size ranged from 0.60 to 0.74. CCE showed high sensitivity and specificity for detecting LV and RV systolic dysfunction and pericardial effusion, with values ranging from 0.85 to 0.99. The kappa statistic for detecting RV dilation was 0.59, with a sensitivity of 0.71 and a specificity of 0.85. In contrast, CCE examinations were nondiagnostic for mitral, tricuspid, or aortic insufficiency in 60–70% of cases, whereas TTE examinations were nondiagnostic in 20–30% of cases. Kappa statistics for mitral, tricuspid, and aortic insufficiency ranged from 0.32 to 0.42. Conclusions: CCE is a reliable tool for assessing LV and RV systolic function, pericardial effusion, and RV size. However, CCE may be limited in its ability to detect mitral, tricuspid, or aortic insufficiency.

Pulmonary Embolism Successfully Treated with Tenecteplase: A case report

Acute pulmonary embolism is a life-threatening situation when presenting with hypotension is called high-risk (massive) pulmonary embolism (PE) which is associated with mortality, especially if there is hemodynamic instability, right ventricular dysfunction with thrombus. Thrombolytic therapy can be lifesaving and leads faster improvement in hemodynamics in patients with acute pulmonary embolism and cardiogenic shock which accelerates the resolution of thrombus, reduction of RV dilatation, mortality and recurrent PE. Only three fibrinolytic agents namely Recombinant tissue-type plasminogen activator (rtPA), Streptokinase and Urokinase have been approved in the treatment of PE. We report the case of a 64 years old Bangladeshi female with a history of immobilization due to unilateral cut injury of foot, who presented with shortness of breath and intermittent chest pain for a duration of 7 days during OPD visit. ECG showed sinus tachycardia (HR-120bpm, regular) and poor progression of R wave. Echocardiography revealed dilated RV, PA with RV dysfunction, presence of McConnell’s sign, RV apical &amp; PA thrombus, flattened IVS, PHT, and minimal pericardial effusion, normal LV systolic function which was reported as suspected pulmonary embolism. Urgent hospitalization and CT pulmonary angiogram (CTPA) was done for confirmatory diagnosis which revealed large pulmonary thrombus in both right and left pulmonary artery. Thrombolysis with Tenecteplase (100ml) over 2 hours was started immediately along with intravenous normal saline and norepinephrine for hypotension, although, it was not recommended by the European Society of Cardiology (ESC) guideline, resulting a successful resolution of the PA thrombus and clinical improvement. She was discharged with oral anticoagulant Rivaroxaban. Bangladesh Heart Journal 2023; 38(2): 148-154

Impact of graft reperfusion on cardiac function assessed by transesophageal echocardiography during liver transplantation: an observational retrospective study

Cardiovascular instability is common during the reperfusion phase of orthotopic liver transplantation (OLT), and some patients experience a postreperfusion syndrome (PRS). However, there are no reports comparing the cardiac dysfunction between patients with PRS and those without. Thus, the aim of this study was to evaluate cardiac dysfunction in patients exhibiting PRS. This observational retrospective study included 34 patients who underwent OLT and were monitored with transesophageal echocardiography (TEE). The right ventricular/left ventricular (RV/LV) end diastolic area, tricuspid annular plane systolic excursion (TAPSE), left ventricular ejection fraction (LVEF) by Simpson method, pulsed Doppler of the mitral valve, and tissue Doppler motion of the mitral annulus were determined. Echocardiographic measurements were registered at the beginning of surgery and at 1 and 30 min after vascular unclamping. Patients with PRS (PRS group) were identified, and their echocardiographic parameters of ventricular function were compared with those in patients without PRS (non-PRS group). To check the evolution of diastolic-systolic dysfunction, general linear model-repeated measures were estimated. No patient presented systolic/diastolic dysfunction on the basal echocardiogram. One minute after vascular unclamping, the incidence of RV dilation was 4.5 times greater in patients with PRS (Cramer´s V > 0.6), and the incidence of RV systolic dysfunction was 62.5% in patients with PRS compared to 15.40% in patients without PRS (Cramer´s V = 0.45). The incidence of LV systolic dysfunction was 25% in patients with PRS compared to 0% in those without (Cramer´s V = 0.45), and left ventricular diastolic dysfunction was 4.8 times greater in patients with PRS (Cramer´s V = 0.45). No patient presented diastolic dysfunction type III. There were significant differences between groups in the evolutionary pattern at 1 and 30 min after unclamping for RV dilation (p = 0.008) and for TAPSE (p = 0.014). Liver graft reperfusion may alter cardiac function. Cardiac dysfunction was more frequent in patients with PRS. These patients exhibited temporary dysfunction of the RV associated with a varying degree of LV diastolic-systolic dysfunction. Trial registration: clinicaltrials.gov (NCT05175534). January 03, 2022; “retrospectively registered”.

Right ventricular dysfunction after therapy titration, but not at the time of index hospitalization, predicts prognosis in patients with new-onset acute heart failure

Abstract Introduction and aims The prognostic implications of right ventricular dysfunction (RVD) in patients with left ventricular (LV) disease has gained more attention over the last years. However, the role of RV function in new-onset acute heart failure (NoAHF) has only recently come into focus. The description of RVD is often confined to its longitudinal function. In the present study of patients with NoAHF, we aimed at (I) comparing the prognostic ability of RV longitudinal function with a novel echocardiographic RVD score and (II) to test the hypothesis that RVD conveys more prognostic information if it persists after titration of heart failure therapy. Methods Patients aged 18 to 70 years, admitted between 2015 and 2018 to a tertiary center with NoAHF were retrospectively included, provided that they did not have previous heart failure diagnosis or therapy and that complete echocardiograms were available at the time of index hospital admission and after titration of heart failure therapy. The RVD score allocates one point each for tricuspid annular plane systolic excursion (TAPSE) &amp;lt;17 mm (longitudinal dysfunction), right ventricular diastolic area index &amp;gt;11.5 (women) or &amp;gt;12.6 cm2/m2 (men) (RV dilatation), ≥moderate tricuspid regurgitation (RV deformation) and vena cava inferior collapsibility &amp;lt;50% (increased right atrial pressure). An RVD score ≥2 was defined as significant RVD. Patients were followed for the composite endpoint of death from all causes, heart transplantation or implantation of LV assist device until September 2022. Results Two-hundred and ten patients were followed for a median of 60 months. At index hospitalization, LV ejection fraction (LVEF) was 28±10%, TAPSE was 16±4 mm and 36% of the patients had a RVD score ≥2. Eighty-eight percent of the patients had LVEF&amp;lt;40%. At the end of the follow-up, 53 (25%) patients met the endpoint. At index hospitalization, there were no significant differences in any echocardiographic parameters between patients meeting and not meeting the endpoint. After titration of heart failure therapy, there were significant differences in LVEF (33% vs 46%, P&amp;lt;0.001), TAPSE (16 vs 19 mm, P = 0.001) and the proportion of patients with RVD score ≥2 (4% vs 36%, P&amp;lt;0.001). Figure 1 and 2 show Kaplan-Meier curves for survival free of composite endpoint in patients with and without RVD despite therapy titration, defined as TAPSE &amp;lt;17 mm or as RVD score ≥2. The unadjusted hazard ratio (95% CI) for TAPSE was 2.5 (1.5-4.4) and for RVD score 7.9 (4.4-14.0). Conclusions At index hospitalization, neither LVEF nor RV function can predict the prognosis in patients with NoAHF. However, the persistence or onset of RV dysfunction after titration of heart failure therapy does. A multiparametric echocardiographic RVD score might provide improved prognostic stratification when compared to TAPSE.Kaplan-Meier, TAPSE≥17mm vs &amp;lt;17mmKaplan-Meier, RVDS&amp;lt;2 vs ≥2

Abstract 18520: Impaired Ubiquitin-Proteasome Function in Right Ventricular Myocardium Correlates to Postoperative Outcomes in Tetralogy of Fallot

Introduction: At the time of initial repair, patients with Tetralogy of Fallot (TOF) undergo a sudden shift from a pressure to volume loaded right ventricle (RV). It is difficult to predict how TOF RVs will respond to this hemodynamic transition. Identifying mechanisms and targets may enable interventions to improve outcomes. Hypothesis: RV myocardial gene expression profiles at the time of TOF repair correlate to pre- and early postoperative clinical outcomes. Methods: RNAseq was performed from RV myocardium resected at the time of initial TOF repair (n=44). Gene expression profiling was performed using a weighted gene correlation network analysis (WGCNA) against pre- and post-op clinical variables. Mouse pulmonary artery band (PAB, n=9) stratified by degree of RV dilation was used to correlate pathways. Results: WGCNA identified a gene module that was associated with younger age at repair and worse TOF postop outcomes (prolonged milrinone, decreased right atrial and right ventricular strain) without a concomitant association with preop oxygen saturation. Biological process gene-set enrichment analysis using the 2023 Gene Ontology library revealed enrichment of regulators for ubiquitination, cell cycle/mitosis, DNA repair, microtubule polymerization, and Rho/GTPase. PAB mouse RV demonstrated a RV-dilation severity-dependent increase in bound ubiquitin (R 2 =0.61, p=0.01) and loss of free ubiquitin (R 2 =0.72, p=0.004; Figure). Conclusions: WGCNA reveals a RV myocardial gene expression profile that is associated with preoperative characteristics and early postoperative outcomes, and which is enriched for ubiquitination regulators. The PAB mouse recapitulates a severity-dependent increase in bound ubiquitin and loss of free ubiquitin which is consistent with literature suggesting proteostatic dysfunction and accumulation of misfolded proteins in RVF. Targeting proteostatic disruption prior to TOF repair may improve postoperative outcomes.

Abstract 15728: Incidence and Impact of Right Ventricular Dysfunction in the Outcomes of Septic Shock

Introduction: Sepsis and its associated systemic inflammatory response syndrome in the heart can lead to septic cardiomyopathy. We aim to explore new onset cardiac dysfunction in septic shock patients and its association of right heart dysfunction with hospital outcomes. Hypothesis: Early development of correct ventricular abnormalities due to septic shock may lead to worse hospital outcomes. Methods: We conducted a retrospective study of 102 patients who were hospitalized at the Mayo Clinic between August 2018 and September 2022 with septic shock and had at least one pre-sepsis echo (within one year before admission) and one post-sepsis echo (within seven days of access). Information on patient demographics, comorbidities, echo parameters, and outcomes was collected from our sepsis database and retrospective chart review. Categorical variables were described as percentages and compared by Chi-square test, and continuous variables as medians and compared using an independent sample t-test. Statistical analysis was performed using BlueSky Statistics v10.3.1. Results: Our study included 102 patients with a median age of 68 (55, 78) years, the majority being men (68%) and Caucasians (80%). Between pre- and post-sepsis echos, there was a noticeable decrease in LVEF (60% vs 50.5 %; p=0.002). Moreover, there was an increase in reduced RV function (31.6% vs. 62.6%, p&lt;0.001), reduced LV function (56.5% vs. 85.2%, p=0.048), and RV dilatation (35.8% vs. 51.5%, p=0.03). There was also a noticeable decrease in IVC collapsibility of more than 50% (65.9% vs 22.9%, p&lt;0.001). There was no significance in terms of demographics, comorbidities, and baseline vitals and labs among patients with RV dysfunction and without RV dysfunction except for a lower LVEF (49% vs 62 %, p= 0.004) and decreased &gt;50 % IVC collapsibility (14.5% vs 48%, p=0.005) in RV dysfunction group. We found no differences in hospital mortality, ICU and hospital LOS, or mechanical ventilation requirements amongst patients with RV abnormalities in function and size. Conclusions: Our retrospective study shows that abnormalities in RV function and RV size are commonly observed in the initial week of septic shock. However, such RV abnormalities did not translate into worse hospital outcomes.

Abstract 17616: The Association Between Hypokinetic Left Ventricle And Pulmonary Embolism

Case Description: A 49-year-old male patient working as a public transport driver presented with syncope lasting a few minutes, followed by non-exertional substernal discomfort. He was hemodynamically stable with a normal physical examination. Laboratory tests revealed an elevated D-dimer of 1146 mg/L and troponin peaking at 1.38 ng/mL. CT Pulmonary angiography was performed, revealing a saddle embolus with signs of right heart strain (Figure 1). A transthoracic echocardiogram revealed a left ventricular (LV) ejection fraction (EF) of 31-35%, and moderately decreased left ventricular systolic function. A venous duplex and hypercoagulability workup yielded negative results. Left-heart catheterization showed normal coronary arteries. A repeat transthoracic echocardiogram three days later showed improvement in LV systolic function with an EF of 41-45% and normal LV function. He was discharged on apixaban with appropriate follow-up. Discussion: Saddle embolism is one of the rare but life-threatening forms of pulmonary embolism. It causes RV dilatation and flattening of the interventricular septum towards the left side, decreasing cardiac output via the “Reverse Bernheim Effect". Rarely, it affects LV contractility and LV ejection fraction. Together, this can lead to severe hemodynamic instability and increase the risk of complications like pulmonary infarction, cardiac arrhythmias, and cardiogenic shock. Therefore, clinicians must be aware of this possibility, as early detection and timely treatment improve patient outcomes.

Abstract 13652: Machine Learning Prediction of RV End-Diastolic Volume in Patients With Pulmonary Regurgitation

Introduction: RV end-diastolic volume (RVEDV) by cardiac MRI (cMRI) guides intervention in congenital heart disease. Guideline directed linear and area measurements from two-dimensional echocardiography (2DE) have poor univariable linear correlation with RVEDV. We hypothesized that non-linear modeling of 2DE RV measurements may predict cMRI volume. Aims: We sought to develop a prediction algorithm for RVEDV from guideline-directed RV 2DE measurements. Methods: Patients from 2009 to 2022 with &gt; mild pulmonary regurgitation and cMRI +/- 3 months were included. 2DE measurements were: RV end-diastolic (RVED) apical 4-chamber area, basal RVED diameter (d), mid RVED d, tricuspid annulus d, RVED length; PSLAX proximal RVOT d; PSSAX proximal RVOT d, distal RVOT d. A gradient-boosting decision trees algorithm (XGBoost) regressed cMRI RVEDV (mL) using 2DE inputs (including missing data) with leave-one-out crossvalidation. Predicted RVEDV was BSA-indexed to examine performance at clinical threshold 150 mL/m 2 . Intraclass correlation coefficient (ICC) in 30 samples was measured. Results: Of 243 subjects (median age 21 [IQR 16-31] y, 58% tetralogy of Fallot, 22% congenital pulmonary stenosis s/p intervention), 19% had cMRI RVEDV &gt; 150 mL/m 2 . Missing ranged from 5% (basal RVED d) to 17% (PSSA proximal RVOT), and ICC ranged from 0.46 (basal RVED d) to 0.78 (tricuspid annulus). Mean absolute error was 40 mL (27 mL/m 2 ). At the predicted threshold 150 mL/m 2 had 39% sensitivity, 87% specificity, 40% positive predictive value, and 86% negative predictive value for true RV dilation. Conclusion: Prediction of RVEDV from guideline recommended 2DE RV measurements is possible. Detection of clinically significant RV dilation has low sensitivity but may be helpful in ruling out cases. Sources of error include interrater variability and missing data due to poor visualization of the RV on 2DE. Future work to develop a consistent and informative feature set for modeling is required.

Abstract 17742: Anterior Papillary Muscle Rupture After a Motor Vehicle Collision: A Rare Case of Torrential Tricuspid Regurgitation After Blunt Cardiac Injury

Introduction: Blunt cardiac injury is difficult to diagnose in the setting of polytrauma. Here we present a rare case of a torrential tricuspid regurgitation from a ruptured anterior papillary muscle after a motor vehicle collision (MVC). Case: A 55-year-old male presented to the ED after an MVC. He was hemodynamically unstable and hypoxic en route complaining of severe chest and left leg pain. Imaging demonstrated multiple rib fractures, a left acetabular fracture, and left open distal femur fracture. EKG identified atrial fibrillation with RVR and nonspecific ST changes. Labs were significant for leukocytosis and a troponin elevation to 11.98 concerning for blunt cardiac injury. A TTE demonstrated a mobile density in the RA and RV consistent with papillary muscle rupture and severe tricuspid regurgitation. An underfilled left ventricle compressed by the right heart and dilated RV were noted with septal flattening consistent with RV pressure and volume overload. Cardiothoracic surgery was consulted and recommended delayed tricuspid valve repair after other acute injuries were addressed considering the need for full anticoagulation. While in the ICU, his orthopedic injuries were addressed though his hemodynamics were complicated by frequent orthopedic interventions requiring blood transfusions. He later underwent TV replacement and it was found that the anterior papillary muscle was ruptured at its base without leaflet perforation. One week post-operatively the patient suffered a hypoxic PEA arrest. The shock team was consulted and he underwent bedside ECMO cannulation with impella placement for LV failure. After ten days on ECMO he was decannulated. Ultimately, the patient recovered well and was discharged to acute rehab. Discussion: MVCs are a leading cause of traumatic tricuspid insufficiency. However, this life-threatening condition may go undetected due polytrauma and the presence of coexisting distracting injuries. Guidelines are needed for the specific management of traumatic tricuspid regurgitation and associated right heart dysfunction. Additionally, the need for multiple surgical interventions can preclude anticoagulation which is a unique barrier to urgent valve replacement in these patients.

Abstract 12001: To Bleed or Not to Bleed: The Challenging Management of Saddle Pulmonary Embolism in a Patient With Widely Metastatic Breast Cancer

Introduction: In patients with high-risk pulmonary embolism (PE), anticoagulation (AC) is the mainstay of treatment before and after systemic thrombolysis and/or catheter-directed therapy. Our case highlights a challenging clinical decision where AC had to be initiated due to hemodynamic instability despite its controversial role in patients with CNS metastases. Case Description: A 52 years old female with ER+/PR+/HER2- breast cancer with widespread brain &amp; vertebral metastases presented after a syncopal event. She had tachycardia and hypotension necessitating IV fluids and vasopressors. Echocardiogram showed RV dilation with reduced systolic function &amp; septal wall motion concerning for RV pressure overload. CTA of chest showed large saddle PE with extension into bilateral segmental arteries and enlarged RV. Significant labs: Troponin-I 1.64 ng/mL, BNP 186 pg/mL, hemoglobin 8 g/dL, and platelets 54,000/μl. She was initiated on IV heparin but given worsening hemodynamic instability, she underwent catheter-based thrombectomy with improvement in hemodynamics. Serial CT head showed no evidence of intracranial hemorrhage but she developed diffuse alveolar hemorrhage necessitating intubation. Her bleeding eventually resolved, and she was extubated and discharged on DOAC. Discussion: This patient had high-risk PE given her hemodynamic instability, elevation in cardiac biomarkers, and RV strain on imaging. Treatment includes AC followed by systemic thrombolysis or catheter-directed therapy followed by AC. This patient’s management was complicated due to widespread metastases, thrombocytopenia and anemia. AC was nonetheless initiated due to her hemodynamic instability and patient eventually required thrombectomy. Conclusion: Brain metastases are an absolute contraindication to systemic thrombolysis, but the role of systemic AC is controversial. Our case highlights the importance of personalized decision-making regarding AC.

Multi-omic and multispecies analysis of right ventricular dysfunction

Right ventricular failure (RVF) is a leading cause of morbidity and mortality in multiple cardiovascular diseases, but there are no treatments for RVF as therapeutic targets are not clearly defined. Contemporary transcriptomic/proteomic evaluations of RVF are predominately conducted in small animal studies, and data from large animal models are sparse. Moreover, a comparison of the molecular mediators of RVF across species is lacking. Transcriptomics and proteomics analyses defined the pathways associated with cardiac magnetic resonance imaging (MRI)-derived values of RV hypertrophy, dilation, and dysfunction in control and pulmonary artery banded (PAB) pigs. Publicly available data from rat monocrotaline-induced RVF and pulmonary arterial hypertension patients with preserved or impaired RV function were used to compare molecular responses across species. PAB pigs displayed significant right ventricle/ventricular (RV) hypertrophy, dilation, and dysfunction as quantified by cardiac magnetic resonance imaging. Transcriptomic and proteomic analyses identified pathways associated with RV dysfunction and remodeling in PAB pigs. Surprisingly, disruptions in fatty acid oxidation (FAO) and electron transport chain (ETC) proteins were different across the 3species. FAO and ETC proteins and transcripts were mostly downregulated in ratsbut were predominately upregulated in PAB pigs, which more closely matched the human response. All species exhibited similar dysregulation of the dilated cardiomyopathy and arrhythmogenic right ventricular cardiomyopathy pathways. The porcine metabolic molecular signature was more similar to human RVF than rodents. These data suggest there may be divergent molecular responses of RVF across species, and pigs may more accurately recapitulate metabolic aspects of human RVF.

Echocardiographic parameters in COVID-19 patients and their association with ICU mortality: a prospective multicenter observational study

BackgroundEchocardiography has become an integral part of the management of critically ill patients. It helps to diagnose and treat various conditions. COVID-19 patients can develop cardiac dysfunction. We planned to study the echocardiographic parameters in COVID-19 patients.MethodsWe conducted a prospective observational multicenter study after institutional ethical committee approval. COVID-19 pneumonia patients admitted to the intensive care unit (ICU) were enrolled. The echocardiographic evaluation was done within 24–48 hours of admission. Assessment of the left and right heart with systolic and left ventricular diastolic function evaluation was done. The primary outcome was ICU mortality. The secondary outcomes were the length of ICU stay and duration of mechanical ventilation.ResultsAmong 573 patients mean age was 57.17 (14.67) with 68.60% being males. On day 1 of ICU, invasive mechanical ventilation was used in 257 (45%) patients. One hundred and forty-eight (25.83%) patients were on vasopressors when echocardiography was performed. Severe left ventricle (LV) systolic dysfunction was seen in 8.7% of patients and had higher odds of mortality [2.48(1.058–5.807), p = 0.037] followed by E and e′ with odds ratio of [0.984(0.971–0.998), p = 0.021] and 0.897 (0.805–0.998), p = 0.046], respectively. E/e′ indicative of filling pressure of the LV was not found to be significant. Troponin I, E/A, and RV dilatation were similar among survivors and non-survivors.ConclusionEchocardiographic evaluation in COVID-19 patients showed severe LV systolic dysfunction was associated with ICU mortality. E/e′ was not found to be significant but lower e′ was associated with higher mortality.Trial registration IEC 131/2020, CTRI/2020/06/025858 date 13th June 2020

A rare cause of mixed hypertrophic and dilated phenotype cardiomyopathy – the MELAS syndrome

Abstract Introduction MELAS is a systemic hereditary condition that can present as hypertrophic or mixed hypertrophic and dilated phenotype cardiomyopathy in young individuals, although a late-onset form is also described in the literature. Genetic testing is essential for correct diagnosis and appropriate management. Case presentation We present the case of a 22-year-old male who was referred to our center after being diagnosed with NYHA class III heart failure with a mixed hypertrophic and dilated cardiomyopathy. His medical history included stroke episodes, seizures, progressive hypoacusis, neurocognitive impairment, and muscle atrophy. Lactic acidosis and elevated CK levels were also noted. The ECG revealed short PR interval and delta wave in lateral leads. TTE showed mildly dilated and hypertrophied LV and RV with severe biventricular systolic impairment. The CMR study was relevant for ring-like subepicardial fibrosis, predominantly in the medium and apical segments. Brain MRI showed multifocal supratentorial subcortical stroke-like lesions in both cerebral hemispheres, involving multiple vascular territories and following a migratory pattern. Genetic testing confirmed a pathogenic MT-TL1 mutation (m.324A&gt;G) and the patient was diagnosed with MELAS. Further management included specific lifestyle recommendations and cascade genetic screening, as well as starting GDMT for HFrEF. Three months after discharge, his clinical status improved. However, the LVEF remained reduced. After careful consideration, an ICD was implanted for primary prevention. Conclusion A red-flag approach in this young patient, which took into consideration the stroke-like episodes, lactic acidosis, seizures, hypoacusis, myopathy, as well as the short PR interval, led to the correct diagnosis, further confirmed by using the appropriate genetic test. Failure to diagnose affects the patient’s prognosis, as their prognosis and clinical status are influenced by enforcing specific recommendations.

Abstract P2135: A Novel Pkp2 Mouse Model Of Genetic Arrhythmogenic Right Ventricular Cardiomyopathy And Its Rescue By Gene Therapy

Background: Arrhythmogenic right ventricular cardiomyopathy (ARVC) is an inherited cardiac disorder in which cardiomyocytes lack structural integrity and signaling is compromised resulting in the disruption of normal rhythms and formation of fibrosis. Patients suffer from arrhythmia and are at increased risk of sudden cardiac death and heart failure. Previous work has demonstrated that heterozygous mutations in the desmosomal gene, plakophilin-2 ( PKP2 ), are the most common cause of ARVC. Our objective was to investigate the mechanisms of ARVC development and test a potential ARVC gene therapy strategy using a novel mouse model of Pkp2. Methods: A knock-in (KI) mouse model with a point mutation corresponding to human PKP2 ( PKP2 c.2146-1G&gt;C or Pkp2 KI) was generated via CRISPR/Cas9 technology. High fat diet (HFD) was used to induce the ARVC phenotype in the Pkp2 KI heterozygous (het) mice. The Pkp2 KI het mice were crossed with a cardiac-specific Pkp2 cKO (αMHC-Cre ERT ) mouse to generate a tamoxifen inducible model (KIxKO). Cardiac function was assessed by echocardiography and arrhythmia burden by EKG. The KIxKO animals received AAV:PKP2 via retro-orbital injection. Results: Pkp2 KI het animals with normal chow had slow and mild ARVC development, and 50% decrease in PKP2 protein expression, with right ventricle (RV) dilation not occurring until animals were 9 months old. Induction with HFD from 8 weeks hastened and worsened the RV dilation. In contrast, the KIxKO mice exhibited &gt;90% decrease in PKP2 protein expression and a correspondingly severe ARVC phenotype starting from 3 weeks after Tamoxifen induction. This included a high arrhythmia burden and both RV area dilation and decreased ejection fraction, indicating the mice eventually progressed to biventricular heart failure. This resulted in 100% mortality in KIxKO animals by 9 weeks post-tamoxifen induction. A single dose of AAV:PKP2 gene therapy (6E13 vg/kg) maintained ejection fraction, prevented ARVC development and improved survival in the KIxKO mice after 9 weeks of treatment. Conclusion: The current results demonstrated that AAV:PKP2 gene therapy may be a promising therapeutic approach to treat ARVC patients with PKP2 mutations resulting in haploinsufficiency.

Abstract P2029: Ror2-mediated Proteostatic Disruption As A Novel Mechanism For Right Ventricular Failure

No therapies exist to reverse right ventricular failure (RVF), in part because RVF molecular drivers have been incompletely characterized. We recently identified RVF-severity dependent re-expression of the developmental noncanonical WNT receptor Ror2 in dilated and ischemic cardiomyopathy RV. We now demonstrate that Ror2 plays a novel role in regulating cardiomyocyte proteostasis (Figure). NRVMs with Ror2 overexpression (Ror2 OE ) are smaller, rounder and demonstrate fragmented sarcomeres, loss of intercalated disc proteins, and reduced ubiquitination. Knockdown of Ror2 (Ror2 KD ) reveals opposing phenotypes. RNAseq of Ror2 OE vs Ror2 KD revealed striking downregulation of chaperone genes (Hspa1a/b, Cryab, Hsp90aa1, Hsph1/d1, etc.) and upregulation of genes involved in proteolysis (Rcn3, Nkd2, Mapk12). Using Suc-LLVY-AMC and GFP-degron, we find that proteasome activity is enhanced in Ror2 OE and inhibited in Ror2 KD . MG-132 proteasomal inhibition reversed structural phenotypes in Ror2 OE NRVMs. In vivo cardiac Ror2 OE caused RV dilation and systolic and diastolic dysfunction, more prominently in male mice. In male Ror2 OE RVs, proteasome activity was enhanced and ubiquitin staining of RV cardiomyocytes was reduced. Finally, PAB caused a 5-fold increase in triton soluble and 40-fold increase in triton insoluble Ror2 expression, which correlated to severity of RV hypertrophy and dilation. Studies to test the efficacy of Ror2 KD for PAB RVF are ongoing. In sum, our work suggests that reactivation on non-canonical Wnt signaling contributes to RVF, unveiling a novel potential therapeutic target.

Cone repair after tricuspid valve replacement in Ebstein anomaly.

Cone repair after tricuspid valve replacement in Ebstein anomaly.