Right Ventricular Dysfunction Research Articles

New Incremental Model for Predicting Mortality in Pre-Capillary Pulmonary Hypertension.

In pulmonary hypertension (PH), the identification of easily obtainable prognostic markers associated with right ventricular (RV) dysfunction and survival is needed. To evaluate the association of red cell distribution width (RDW) with clinical, echocardiographic parameters and survival in patients with pre-capillary PH, with the development of a mortality prediction model. Observational, longitudinal, and prospective study conducted from May 2019 to December 2022. Thirty-four patients with pre-capillary PH underwent two-dimensional echocardiography and complete blood count. A cutoff point of 14.5% was considered to define RDW as altered (≥14.5%) or normal (<14.5%). P values <0.05 were considered significant. The median RDW was 14.4%. There was a significant difference in peripheral arterial oxygen saturation (SpO2) (p=0.028), RV strain (p=0.047), and pericardial effusion (p=0.002) between the normal and elevated RDW groups. During a median follow-up of 15 months, 20.6% died. Patients with increased RDW had a shorter overall survival (44.7%, log-rank p=0.019), which was a predictor of mortality in univariate Cox regression (HR 8.55, p=0.048). The addition of RV strain <16% and SpO2 ≤93% to the model including RDW alone showed incremental value in predicting mortality (χ2=8.2, p=0.049; χ2=12.4, p=0.041), with increased area under the receiver operating characteristic curve (0.729 vs. 0.837 vs. 0.909) and decreased probability of survival (44.7% vs. 35.6% vs. 25%, log-rank p=0.019). RDW provides information on the severity of pre-capillary PH by correlating with echocardiographic parameters of RV dysfunction and mortality, which is best predicted by a model including RDW, RV strain and SpO2.

Right ventricular fibrosis in adults with uncorrected secundum atrial septal defect and pulmonary hypertension: a cardiovascular magnetic resonance study with late gadolinium enhancement, native T1 and extracellular volume.

Right ventricular (RV) fibrosis represents both adaptive and maladaptive responses to the overloaded RV condition. Its role in pulmonary hypertension (PH) associated with secundum atrial septal defect (ASD), which is the most common adult congenital heart disease (CHD), remains poorly understood. We enrolled 65 participants aged ≥18 years old with uncorrected secundum ASD who had undergone clinically indicated right heart catheterization (RHC), divided into the non-PH group (n = 7), PH group (n = 42), and Eisenmenger syndrome (ES) group (n = 16). We conducted cardiovascular magnetic resonance (CMR) studies with late gadolinium enhancement (LGE) imaging, native T1 mapping, and extracellular volume (ECV) measurement to evaluate the extent and clinical correlates of RV fibrosis. LGE was present in 94% of the population and 86% of the non-PH group, mostly located at the right ventricular insertion point (RVIP) regions. LGE in the septal and inferior RV region was predominantly observed in the ES group compared to the other groups (p = 0.031 and p < 0.001, respectively). The mean LGE scores in the ES and PH groups were significantly higher than those in the non-PH group (3.38 ± 0.96 vs. 2.74 ± 1.04 vs. 1.57 ± 0.79; p = 0.001). The ES and PH groups had significantly higher degrees of interstitial RV fibrosis compared to those in the non-PH group, indicated by native T1 (1,199.9 ± 68.9 ms vs. 1,131.4 ± 47.8 ms vs. 1,105.4 ± 44.0 ms; p < 0.001) and ECV (43.6 ± 6.6% vs. 39.5 ± 4.9% vs. 39.4 ± 5.8%; p = 0.037). Additionally, native T1 significantly correlated with pulmonary vascular resistance (r = 0.708, p < 0.001), RV ejection fraction (r = -0.468, p < 0.001) and peripheral oxygen saturation (r = -0.410, p = 0.001). In patients with uncorrected secundum ASD, RV fibrosis may occur before the development of PH and progressively intensify alongside the progression of PH severity. A higher degree of RV fibrosis, derived from CMR imaging, correlates with worse hemodynamics, RV dysfunction, and poorer clinical conditions.

The Sugen/Hypoxia Rat Model for Pulmonary Hypertension and Right Heart Failure.

Pulmonary hypertension (PH) is a devastating disease, characterized by complex remodeling of the pulmonary vasculature. PH is classified into five groups based on different etiology, pathology, as well as therapy and prognosis. Animal models are essential for the study of underlying mechanisms, pathophysiology, and preclinical testing of new therapies for PH. The complexity of the disease with different clinical entities dictates the necessity for more than one animal model to resemble PH, as a single model cannot imitate the broad spectrum of human PH.Here we describe a detailed protocol for creating a rat model of PH with right ventricular (RV) failure. Furthermore, we present how to characterize it hemodynamically by invasive measurements of RV and pulmonary arterial (PA) pressures. Animals subjected to this model display severe pulmonary vascular remodeling and RV dysfunction. In this model, rats undergo a single subcutaneous injection of Sugen (SU5416, a vascular endothelial growth factor inhibitor) and are immediately exposed to chronic hypoxia in a hypoxia chamber for 3-6weeks. This Sugen/Hypoxia rat model resembles Group 1 PH.

The Prognostic Value of Right Ventricle Strain In Patients With Heart Failure With Reduced Ejection Fraction (HFrEF)

Background: RV dysfunction has been recognized as a powerful independent predictor of poor prognosis. Therefore, accurate evaluation of RV function is helpful for risk stratification in patients with HF, so as to guide clinicians to choose the best treatment and improve the prognosis of patients. Therefore, assessment of RV function is clinically important in almost all patients with heart disease. Objective: The main purpose of this study was to evaluate the prognostic value of right ventricular free wall longitudinal strain in patients with heart failure with reduced ejection fraction (HFrEF). Methods: We evaluated a prospective cohort of 126 patients with known or suspected HFrEF referred for echocardiographic evaluation. All underwent measurement of RV free-wall longitudinal strain (RVFWLS) by 2D transthoracic echocardiography. The primary study endpoint was the occurrence of death for any cause or hospitalization for heart failure. Results: From 126 eligible patients with chronic heart failure, 10 (8%) with RVFWLS not suitable for strain analysis were excluded, leaving a final study population of 116 patients. During the follow-up period of 24 months, 44 patients (38%) reached the composite end point: 18 patients died (15%), and 26 patients (22%) were hospitalized for worsening HF. Compared with patients without events, patients who reached the composite end point were older and prevalently men (P &lt;0.05). Patients with events also showed higher LV volumes, lower LVEF%, increased left atrial volume index (LAVI), increased pulmonary artery systolic pressure, and higher prevalence of severe MR and TR than event-free patients. Diastolic RV diameter was also significantly greater in this group. In this study, we found that a RVFWLS less negative of -19.3% was associated to outcomes with 75% sensitivity and 67% specificity P &lt; 0.001. A value of RVFWLS less than -19.3% was strongly associated to outcome with HR 1.9, 95% CI 1.487–2.7; P &lt; 0.001. Conclusion: RV free wall longitudinal strain seems to be more sensitive and accurate for the diagnosis of RV systolic dysfunction in patients with HFrEF, therefore assessment of RV function should be implemented by analysis of RVFWLS in patients with HFrEF, to improve identification of patients who are at high risk for adverse events.

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.

Time to assess more than prognosis: advancements and challenges in transcatheter tricuspid valve interventions.

We provide an overview about the current landscape of transcatheter tricuspid valve interventions (TTVI) and summarize recent findings from trials including TRILUMINATE, TRILUMINATE Pivotal, bRIGHT, TRICLASP, TRISCEND, TRISCEND II, TRICUS, and Cardioband TR EFS. These studies have demonstrated the safety and efficacy of TTVI. Yet, they have failed to show a prognostic benefit over conservative treatment. On the other hand, significant improvements in health status assessments have been observed. Assessment of right ventricular (RV) function prior to tricuspid interventions is crucial, as changes in preload and afterload may lead to RV failure which is associated with a high mortality. Therefore, this review emphasizes the impact of TTVIs on quality of life and explores the influence of RV dysfunction on therapeutic success and prognosis.

A multimodal approach identifies lactate as a central feature of right ventricular failure that is detectable in human plasma.

In PAH metabolic abnormalities in multiple pathways are well-recognized features of right ventricular dysfunction, however, prior work has focused mainly on the use of a single "omic" modality to describe a single deranged pathway. We integrated metabolomic and epigenomic data using transcriptomics in failing and non-failing RVs from a rodent model to provide novel mechanistic insight and translated these findings to accessible human specimens by correlation with plasma from PAH patients. Study was conducted in a doxycycline-inducible BMPR2 mutant mouse model of RV failure. Plasma was collected from controls and PAH patients. Transcriptomic and metabolomic analyses were done on mouse RV tissue and human plasma. For mouse RV, we layered metabolomic and transcriptomic data for multiple metabolic pathways and compared our findings with metabolomic and transcriptomic data obtained for human plasma. We confirmed our key findings in cultured cardiomyocyte cells with BMPR2 mutation. In failing mouse RVs, (1) in the glycolysis pathway, glucose is converted to lactate via aerobic glycolysis, but may also be utilized for glycogen, fatty acid, and nucleic acid synthesis, (2) in the fatty acid pathway, FAs are accumulated in the cytoplasm because the transfer of FAs to mitochondria is reduced, however, the ß-oxidation pathway is likely to be functional. (3) the TCA cycle is altered at multiple checkpoints and accumulates citrate, and the glutaminolysis pathway is not activated. In PAH patients, plasma metabolic and transcriptomic data indicated that unlike in the failing BMPR2 mutant RV, expression of genes and metabolites measured for the glycolysis pathway, FA pathway, TCA cycle, and glutaminolysis pathway were increased. Lactate was the only metabolite that was increased both in RV and circulation. We confirmed using a stable isotope of lactate that cultured cardiomyocytes with mutant BMPR2 show a modest increase in endogenous lactate, suggesting a possibility of an increase in lactate production by cardiomyocytes in failing BMPR2 mutant RV. In the failing RV with mutant BMPR2, lactate is produced by RV cardiomyocytes and may be secreted out, thereby increasing lactate in circulation. Lactate can potentially serve as a marker of RV dysfunction in PAH, which warrants investigation.

Outcomes of Children With Hypoplastic Left Heart Syndrome and Heart Failure on Medical Therapy

BackgroundSystemic right ventricle (RV) dysfunction is associated with lower transplant-free survival (TFS) in hypoplastic left heart syndrome (HLHS), but the likelihood of functional improvement and utility of heart failure (HF) medications is not understood. ObjectivesThe authors aimed to describe TFS, HF medication use, and surgical interventions in HLHS patients with RV dysfunction with and without subsequent improvement in function. MethodsThe SickKids HF Database is a retrospective cohort that includes all pediatric HLHS patients with RV dysfunction lasting >30 days. We compared TFS, HF medications, and surgical interventions in HLHS patients with and without functional normalization. ResultsOf 99 patients with HLHS and RV dysfunction, 52% had normalized function for ≥30 days. TFS at 2 years after dysfunction onset was lower in those without normalization (14% vs 78%, P < 0.001). Patients without normalization were less likely to reach target dosing (TD) of HF medications (27% vs 47% on 1 medication at TD, P < 0.001) and undergo Fontan completion (7% vs 53%, P < 0.001). Clinical factors associated with improved TFS were normalization of function for ≥30 days, onset of dysfunction after bidirectional Glenn, and exposure to ACE inhibition. ConclusionsOur cohort of HLHS patients with systemic RV dysfunction demonstrated a novel finding of improved TFS in those with functional normalization for ≥30 days. Achieving TD of HF medications was associated with improved outcomes. This may reflect patient stability and tolerance for HF medication more than its therapeutic effect, but it can help inform decisions to proceed with surgical palliation or list for transplant.

Effect of left bundle branch pacing on right ventricular function: A 3-dimensional echocardiography study

BackgroundThe effect of left bundle branch pacing (LBBP) on right ventricular (RV) function is not well known, and there is conflicting evidence regarding whether cardiac resynchronization therapy improves RV function. ObjectivesThe study aimed to investigate the effect of LBBP on RV function and to evaluate the response of RV dysfunction (RVD) to LBBP. MethodsSixty-five LBBP candidates were prospectively included in the study and underwent echocardiography at baseline and 6-month follow-up. LBBP response was left ventricular (LV) reverse remodeling, defined as a reduction in LV end-systolic volume of ≥15% at follow-up. ResultsPatients were assigned to 2 subgroups on the basis of 3-dimensional echocardiography–derived RV ejection fraction (EF) before LBBP implantation: 30 patients (46%) in the no RVD group and 35 patients (54%) in the RVD group. The RVD group was characterized by higher N-terminal pro–brain natriuretic peptide levels, New York Heart Association functional class, and larger LV/RV size. LBBP induced a significant reduction in QRS duration, LV size, and improvement in LVEF and mechanical dyssynchrony in both the no RVD and RVD groups, and a significant improvement in RV volumes and RVEF in the RVD group (all P<.01). LBBP resulted in a similar percentage reduction in QRS duration, LV dimensions, LV volumes, and percentage improvement in LVEF in RVD and no RVD groups (all P＞.05). LV reverse remodeling (29 of 35 patients vs 27 of 30 patients; P = .323) in the RVD group was similar to that in the no RVD group after LBBP. ConclusionLBBP induces excellent electrical and mechanical resynchronization, with a significant improvement in RV volumes and function. RVD did not diminish the beneficial effects on LV reverse remodeling after LBBP.

An attention-based deep learning method for right ventricular quantification using 2D echocardiography: Feasibility and accuracy.

To test the feasibility and accuracy of a new attention-based deep learning (DL) method for right ventricular (RV) quantification using 2D echocardiography (2DE) with cardiac magnetic resonance imaging (CMR) as reference. We retrospectively analyzed images from 50 adult patients (median age 51, interquartile range 32-62 42% women) who had undergone CMR within 1 month of 2DE. RV planimetry of the myocardial border was performed in end-diastole (ED) and end-systole (ES) for eight standardized 2DE RV views with calculation of areas. The DL model comprised a Feature Tokenizer module and a stack of Transformer layers. Age, gender and calculated areas were used as inputs, and the output was RV volume in ED/ES. The dataset was randomly split into training, validation and testing subsets (35, 5 and 10 patients respectively). Mean RVEDV, RVESV and RV ejection fraction (EF) were 163±70mL, 82±42mL and 51%±8% respectively without differences among the subsets. The proposed method achieved good prediction of RV volumes (R2 =.953, absolute percentage error [APE]=9.75%±6.23%) and RVEF (APE=7.24%±4.55%). Per CMR, there was one patient with RV dilatation and three with RV dysfunction in the testing dataset. The DL model detected RV dilatation in 1/1 case and RV dysfunction in 4/3 cases. An attention-based DL method for 2DE RV quantification showed feasibility and promising accuracy. The method requires validation in larger cohorts with wider range of RV size and function. Further research will focus on the reduction of the number of required 2DE to make the method clinically applicable.

Advanced hemodynamic and cluster analysis for identifying novel RV function subphenotypes in patients with pulmonary hypertension

BackgroundQuantifying right ventricular (RV) function is important to describe the pathophysiology of in pulmonary hypertension (PH). Current phenotyping strategies in PH rely on few invasive hemodynamic parameters to quantify RV dysfunction severity. The aim of this study was to identify novel RV phenotypes using unsupervised clustering methods on advanced hemodynamic features of RV function. MethodsParticipants were identified from the University of Arizona Pulmonary Hypertension Registry (n=190). RV-pulmonary artery coupling (Ees/Ea), RV systolic (Ees) and diastolic function (Eed) was quantified from stored RV pressure waveforms. Consensus clustering analysis with bootstrapping was used to identify the optimal clustering method. Pearson correlation analysis was used to reduce collinearity between variables. RV cluster subphenotypes were characterized using clinical data and compared to pulmonary vascular resistance (PVR) quintiles. ResultsFive distinct RV clusters (C1-C5) with distinct RV subphenotypes were identified using k-medoids with a Pearson distance matrix. Clusters 1 and 2 both have low diastolic stiffness (Eed) and afterload (Ea) but RV-PA coupling (Ees/Ea) is decreased in C2. Intermediate cluster (C3) has a similar Ees/Ea as C2 but with higher PA pressure and afterload. Clusters C4 and C5 have increased Eed and Ea but C5 has a significant decrease in Ees/Ea. Cardiac output was high in C3 distinct from the other clusters. In the PVR quintiles, contractility increased and stroke volume decreased as a function of increased afterload. World Symposium PH classifications were distributed across clusters and PVR quintiles. ConclusionsRV-centric phenotyping offers an opportunity for a more precise-medicine based management approach.

Prevalence of Cardiac Sarcoidosis in Middle-Aged Adults Diagnosed with High-Grade Atrioventricular Block

IntroductionAtrioventricular block may be idiopathic or a secondary manifestation of an underlying systemic disease. Cardiac sarcoidosis is a significant underlying cause of high-grade atrioventricular block, posing diagnostic challenges and significant clinical implications. This study aimed to assess the prevalence and clinical characteristics of cardiac sarcoidosis among younger patients presenting with unexplained high-grade atrioventricular block. MethodsWe evaluated patients aged between 18 and 65 years presenting with unexplained high-grade atrioventricular block, who were systematically referred for cardiac magnetic resonance imaging, positron emission tomography-computed tomography, or both, prior to pacemaker implantation. Subjects with suspected cardiac sarcoidosis based on imaging findings were further referred for tissue biopsy. Cardiac sarcoidosis diagnosis was confirmed based on biopsy results. ResultsOverall, 30 patients with high-grade atrioventricular block were included in the analysis. The median age was 56.5 years (interquartile range 53-61.75, years). In 37%, cardiac magnetic resonance imaging, positron emission tomography-computed tomography, or both, were suggestive of cardiac sarcoidosis, and in 33% cardiac sarcoidosis was confirmed by tissue biopsy. Compared with idiopathic high-grade atrioventricular block patients, all cardiac sarcoidosis patients were males (100% vs 60%, P = .029), were more likely to present with heart failure symptoms (50% vs 10%, P = .047), had thicker inter-ventricular septum on echocardiography (12.2 ± 2.7 mm vs 9.45 ± 1.6 mm, P = .002), and were more likely to present with right ventricular dysfunction (33% vs 10%, P = .047). ConclusionsCardiac sarcoidosis was confirmed in one-third of patients ≤ 65 years, who presented with unexplained high-grade atrioventricular block. Cardiac sarcoidosis should be highly suspected in such patients, particularly in males who present with heart failure symptoms or exhibit thicker inter-ventricular septum and right ventricular dysfunction on echocardiography.

Effects of empagliflozin on right ventricular adaptation to pressure overload.

Right ventricular (RV) failure is the prime cause of death in patients with pulmonary arterial hypertension. Novel treatment strategies that protect the RV are needed. Empagliflozin, a sodium-glucose co-transporter-2 inhibitor, shows cardioprotective effects on the left ventricle in clinical and preclinical studies, but its direct effects on RV remain elusive. We investigated the effects of empagliflozin on RV dysfunction induced by pulmonary trunk banding (PTB). Male Wistar rats (116 ± 10 g) were randomized to PTB or sham surgery. One week after surgery, PTB animals received empagliflozin mixed into the chow (300 mg empagliflozin/kg chow; PTB-empa, n = 10) or standard chow (PTB-control, n = 10). Sham rats (Sham, n = 6) received standard chow. After five weeks, RV function was evaluated by echocardiography, cardiac MRI, and invasive pressure-volume measurements. PTB caused RV failure evident by decreased cardiac output compared with sham. PTB-empa rats had a 49% increase in water intake compared with PTB-control yet no differences in hematocrit or blood glucose. Treatment with empagliflozin decreased RV end-systolic pressures without any changes in RV cardiac output or ventricular-arterial coupling (Ees/Ea). The decrease in RV end-systolic pressure was complemented by a slight reduction in RV cross sectional area as a sign of reduced hypertrophy. Load-independent measures of RV systolic and diastolic function were not affected in PTB-empa rats compared with PTB-control. Empagliflozin treatment reduced RV end-systolic pressure in RV failure induced by pressure overload. Further studies are needed to elucidate whether this simply relates to a diuretic effect and/or additional independent beneficial RV effects.

Relationship between Plasma D-Dimer Level and Pulmonary Hypertension as well as Right Ventricle Dysfunction in Patient Post Pneumonia COVID-19

Background: High rate of coagulopathy and pulmonary thromboembolism in coronavirus disease 2019 (COVID-19), which is represented by an increase in plasma D-Dimer levels is believed to be related to pulmonary hypertension (PH) and right ventricle (RV) dysfunction. Objective: To evaluate the relationship between plasma D-Dimer levels with PH and RV dysfunction assessed from transthoracic echocardiography (TTE) in patients post COVID-19 pneumonia. Methods: Observational research with a cross-sectional design. Estimated mean pulmonary arterial pressure (mPAP) was calculated from Mahan's formula obtained from pulmonary artery acceleration time (PAAT) and RV function was assessed from RV free wall strain (RV FWS), tricuspid annular plane systolic excursion (TAPSE), and fractional area change (FAC). D-Dimer levels during hospitalisation were obtained from medical records and actual D-Dimer was obtained at the time of echocardiography. Results: Total 40 patients post-COVID-19 pneumonia underwent TTE in a median of 11 days after negative PCR. There was a significant correlation between peak D-Dimer levels with mPAP (r=0.526, p&lt;0.001), RV FWS (r=-0.506, p=0.001), TAPSE (r=-0.498, p=0.001), and FAC (r=0.447, p=0.004). Multivariate analysis found peak D-Dimer ≥4530 µg/L independently associated with PH with odds ratio (OR) 6.6, (95% CI 1.1-10; p=0.048), but not with RV dysfunction. Conclusion: Peak D-Dimer level correlates with echocardiographic parameters of RV function and mPAP in patients with COVID-19 infection. Peak D-Dimer ≥4530 µg/L might increase risk of PH, but not RV dysfunction in patient post pneumonia COVID-19.

CILP-1 Is a Biomarker for Backward Failure and Right Ventricular Dysfunction in HFrEF.

CILP-1 regulates myocardial fibrotic response and remodeling and was reported to indicate right ventricular dysfunction (RVD) in pulmonary hypertension (PH) and heart failure (HF). This study examines CILP-1 as a potential biomarker for RVD and prognosis in heart failure with reduced ejection fraction (HFrEF) patients on guideline-directed medical therapy. CILP-1 levels were measured in 610 HFrEF patients from a prospective registry with biobanking (2016-2022). Correlations with echocardiographic and hemodynamic data and its association with RVD and prognosis were analyzed. The median age was 62 years (Q1-Q3: 52-72), 77.7% of patients were male, and the median NT-proBNP was 1810 pg/mL (Q1-Q3: 712-3962). CILP-1 levels increased with HF severity, as indicated by NT-proBNP and NYHA class (p < 0.0001, for both). CILP-1 showed a weak-moderate direct association with increased left ventricular filling pressures and its sequalae, i.e., backward failure (LA diameter rs = 0.15, p = 0.001; sPAP rs = 0.28, p = 0.010; RVF rs = 0.218, p < 0.0001), but not with cardiac index (CI) and systemic vascular resistance (SVR). CILP-1 trended as a risk factor for all-cause mortality (crude HR for 500 pg/mL increase: 1.03 (95%CI: 1.00-1.06), p = 0.053) but lost significance when it was adjusted for NT-proBNP (adj. HR: 1.00 (95%CI: 1.00-1.00), p = 0.770). No association with cardiovascular hospitalization was observed. CILP-1 correlates with HFrEF severity and may indicate an elevated risk for all-cause mortality, though it is not independent from NT-proBNP. Increased CILP-1 is associated with backward failure and RVD rather than forward failure. Whether CILP-1 release in this context is based on elevated pulmonary pressures or is specific to RVD needs to be further investigated.

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

Management Strategies in Arrhythmogenic Cardiomyopathy across the Spectrum of Ventricular Involvement.

Improved disease recognition through family screening and increased life expectancy with appropriate sudden cardiac death prevention has increased the burden of heart failure in arrhythmogenic cardiomyopathy (ACM). Heart failure management guidelines are well established but primarily focus on left ventricle function. A significant proportion of patients with ACM have predominant or isolated right ventricle (RV) dysfunction. Management of RV dysfunction in ACM lacks evidence but requires special considerations across the spectrum of heart failure regarding the initial diagnosis, subsequent management, monitoring for progression, and end-stage disease management. In this review, we discuss the unique aspects of heart failure management in ACM with a special focus on RV dysfunction.

Right Ventricular Dysfunction on Transthoracic Echocardiography and Long-Term Mortality in the Critically Unwell: A Systematic Review and Meta-Analysis.

Right ventricular dysfunction (RVD) is common in the critically ill. To date studies exploring RVD sequelae have had heterogenous definitions and diagnostic methods, with limited follow-up. Additionally much literature has been pathology specific, limiting applicability to the general critically unwell patient. We conducted a systematic review and meta-analysis to evaluate the impact of RVD diagnosed with transthoracic echocardiography (TTE) on long-term mortality in unselected critically unwell patients compared to those without RVD. A systematic search of EMBASE, Medline and Cochrane was performed from inception to March 2022. All RVD definitions using TTE were included. Patients were those admitted to a critical or intensive care unit, irrespective of disease processes. Long-term mortality was defined as all-cause mortality occurring at least 30 days after hospital admission. A priori subgroup analyses included disease specific and delayed mortality (death after hospital discharge/after the 30th day from hospital admission) in patients with RVD. A random effects model analysis was performed with the Dersimionian and Laird inverse variance method to generate effect estimates. Of 5985 studies, 123 underwent full text review with 16 included (n = 3196). 1258 patients had RVD. 19 unique RVD criteria were identified. The odds ratio (OR) for long term mortality with RVD was 2.92 (95% CI 1.92-4.54, I2 76.4%) compared to no RVD. The direction and extent was similar for cardiac and COVID19 subgroups. Isolated RVD showed an increased risk of delayed mortality when compared to isolated left/biventricular dysfunction (OR 2.01, 95% CI 1.05-3.86, I2 46.8%). RVD, irrespective of cause, is associated with increased long term mortality in the critically ill. Future studies should be aimed at understanding the pathophysiological mechanisms by which this occurs. Commonly used echocardiographic definitions of RVD show significant heterogeneity across studies, which contributes to uncertainty within this dataset.

Tissue Doppler vs. conventional parameters for diagnosis of tamponading pericardial effusion: a cross-sectional study in tertiary referral center

BackgroundConventional signs of tamponade include right ventricular and atrial collapse and respiratory variation in mitral inflow velocities. Despite being reliable, they are qualitative in nature and are not well correlated with clinical signs of deterioration or improvement. Tamponade is invariably preceded and associated with diastolic dysfunction, and tissue Doppler imaging (TDI) can help in early detection of it, earlier than conventional signs. For this purpose, 36 patients presenting with pericardial effusion have been subjected to echocardiography, including effusion dimensions, presence or absence of routine signs of tamponade and TDI-derived LV and RV E/E′ ratios, as well as clinical signs of tamponade to test the diagnostic accuracy of echocardiographic parameters against them.ResultsRight atrial and ventricular collapse were the least accurate in the detection of tamponade, while effusion dimension > 14 mm was the most accurate among conventional parameters to point toward tamponade. RV and LV diastolic dysfunction as evidenced by E/E′ ratio showed 100% sensitivity in predicting tamponade, while LV E/E′ ratio showed the highest specificity (100%) in the same context. The higher diagnostic accuracy of LV E/E′ ratio might be also related to the presence of chronic kidney disease patients, with an already jeopardized LV function.ConclusionsTDI technology is now available in most of the portable echocardiography machines and can serve as part of point-of-care echocardiography in the early detection of cardiac tamponade and in decision making for pericardiocentesis. Larger studies can help in consolidating the impression driven from our small-scale cross-sectional study.

Pulmonary Hypertension-Associated Right Ventricular Cardiomyocyte Remodelling Reduces Treprostinil Function.

(1) Pulmonary hypertension (PH)-associated right ventricular (RV) failure is linked to a reduction in pulmonary vasodilators. Treprostinil has shown effectiveness in PAH patients with cardiac decompensation, hinting at potential cardiac benefits. We investigated treprostinil's synergy with isoprenaline in RV and LV cardiomyocytes. We hypothesised that disease-related RV structural changes in cardiomyocytes would reduce contractile responses and cAMP/PKA signalling activity. (2) We induced PH in male Sprague Dawley rats using monocrotaline and isolated their ventricular cardiomyocytes. The effect of in vitro treprostinil and isoprenaline stimulation on contraction was assessed. FRET microscopy was used to study PKA activity associated with treprostinil stimulation in AKAR3-NES FRET-based biosensor-expressing cells. (3) RV cells exhibited maladaptive remodelling with hypertrophy, impaired contractility, and calcium transients compared to control and LV cardiomyocytes. Combining treprostinil and isoprenaline failed to enhance inotropy in PH RV cardiomyocytes. PH RV cardiomyocytes displayed an aberrant contractile behaviour, which the combination treatment could not rectify. Finally, we observed decreased PKA activity in treprostinil-treated PH RV cardiomyocytes. (4) PH-associated RV cardiomyocyte remodelling reduced treprostinil sensitivity, inotropic support, and impaired relaxation. Overall, this study highlights the complexity of RV dysfunction in advanced PH and suggests the need for alternative therapeutic strategies.