Cardiorenal Syndrome in Right Heart Failure Due to Pulmonary Arterial Hypertension-The Right Ventricle as a Therapeutic Target to Improve Renal Function.

Cardiorenal syndrome (CRS) due to right ventricular (RV) failure is a disease entity emerging as a key indicator of morbidity and mortality. The multifactorial aspects of CRS and the left-right ventricular interdependence complicate the link between RV failure and renal function. RV failure has a direct pathophysiological link to renal dysfunction by leading to systemic venous congestion in certain circumstances and low cardiac output in other situations, both leading to impaired renal perfusion. Indeed, renal dysfunction is known to be an independent predictor of mortality in patients with pulmonary arterial hypertension (PAH) and RV failure. Thus, it is important to further understand the interaction between the RV and renal function. RV adaptation is critical to long-term survival in patients with PAH. The RV is also known for its remarkable capacity to recover once the aggravating factor is addressed or mitigated. However, less is known about the renal potential for recovery following the resolution of chronic RV failure. In this review, we provide an overview of the intricate relationship between RV dysfunction and the subsequent development of CRS, with a particular emphasis on PAH. Additionally, we summarize potential RV-targeted therapies and their potential beneficial impact on renal function.

Venoarterial Extracorporeal Membrane Oxygenation Therapy in Patients with Sickle Cell Disease: Case Series and Review for Intensive Care Physicians.

Sickle cell disease (SCD) is associated with substantial morbidity and early mortality in afflicted adults. Cardiopulmonary complications that occur at increased frequency in SCD such as pulmonary embolism, pulmonary arterial hypertension, and acute chest syndrome can acutely worsen right ventricular function and lead to cardiogenic shock. Mechanical circulatory support including venoarterial extracorporeal membrane oxygenation (VA ECMO) is being increasingly utilized to treat hemodynamic collapse in various patient populations. However, a paucity of literature exists to guide the use of mechanical circulatory support in adults with SCD where disease-related sequela and unique hematologic aspects of this disorder may complicate extracorporeal therapy and must be understood. Here, we review the literature and describe three cases of adult patients with SCD who developed cardiogenic shock from acute decompensated right heart failure and were treated clinically with VA ECMO. Using an in vitro ECMO system, we investigate a potential increased risk of systemic fat emboli in patients with SCD who may be experiencing vaso-occlusive events with bone marrow involvement given the high-volume shunting of blood from venous to arterial systems with VA ECMO. The purpose of this study is to describe available extracorporeal life support experiences, review potential complications, and discuss the special considerations needed to further our understanding of the utility of VA ECMO in those with SCD.

HeartMate 3 implantation with an emphasis on the biventricular configuration.

OBJECTIVES: Right ventricular failure following implantation of a durable left ventricular assist device (LVAD) is a major driver of mortality. Reported survival following biventricular (BiVAD) or total artificial heart (TAH) implantation remains substantially inferior to LVAD alone. We report our outcomes with LVAD and BiVAD HeartMate 3 (HM3). METHODS: Consecutive patients undergoing implantation of an HM3 LVAD between November 2014 and December 2021, at The Alfred, Australia were included in the study. Comparison was made between the BiVAD and LVAD alone groups. RESULTS: A total of 86 patients, 65 patients with LVAD alone and 21 in a BiVAD configuration underwent implantation. The median age of the LVAD and BiVAD groups was 56 years (Interquartile range 46-62) and 49 years (Interquartile range 37-55), respectively. By 4 years after implantation, 54% of LVAD patients and 43% of BiVAD patients had undergone cardiac transplantation. The incidence of stroke in the entire experience was 3.5% and pump thrombosis 5% (all in the RVAD). There were 14 deaths in the LVAD group and 1 in the BiVAD group. The actuarial survival for LVAD patients at 1 year was 85% and BiVAD patients at 1 year was 95%. CONCLUSIONS: The application of HM 3 BiVAD support in selected patients appears to offer a satisfactory solution to patients requiring biventricular support.

Concomitant tricuspid valve surgery in patients with significant tricuspid regurgitation undergoing left ventricular assist device implantation: A systematic review and meta-analysis.

BACKGROUND: Significant tricuspid regurgitation (TR) is a predictor of right heart failure (RHF) and increased mortality following left ventricular assist device (LVAD) implantation, however the benefit of tricuspid valve surgery (TVS) at the time of LVAD implantation remains unclear. This study compares early and late mortality and RHF outcomes in patients with significant TR undergoing LVAD implantation with and without concomitant TVS. METHODS: A systematic search of four electronic databases was conducted for studies comparing patients with moderate or severe TR undergoing LVAD implantation with or without concomitant TVS. Meta-analysis was performed for primary outcomes of early and late mortality and RHF. Secondary outcomes included rate of stroke, renal failure, hospital and ICU length of stay. An overall survival curve was constructed using aggregated, reconstructed individual patient data from Kaplan-Meier (KM) curves. RESULTS: Nine studies included 575 patients that underwent isolated LVAD and 308 patients whom received concomitant TVS. Both groups had similar rates of severe TR (46.5% vs. 45.6%). There was no significant difference seen in risk of early mortality (RR 0.90; 95% CI, 0.57-1.42; p = 0.64; I2 = 0%) or early RHF (RR 0.82; 95% CI, 0.66-1.19; p = 0.41; I2 = 57) and late outcomes remained comparable between both groups. The aggregated KM curve showed isolated LVAD to be associated with overall increased survival (HR 1.42; 95% CI, 1.05-1.93; p = 0.023). CONCLUSIONS: Undergoing concomitant TVS did not display increased benefit in terms of early or late mortality and RHF in patients with preoperative significant TR. Further data to evaluate the benefit of concomitant TVS stratified by TR severity or by other predictors of RHF will be beneficial.

Performance of handheld ultrasound devices in diagnosis of pulmonary hypertension and right heart dysfunction in ICU patients.

AIM: The use of handheld ultrasonography devices (HHUD) has increased recently but there are limited data about their performance in the evaluation of right heart dysfunction (RHD) and pulmonary hypertension (PHT). The aim of the study is to compare the performance of a HHUD with a conventional ultrasound device (CUD) in assessing PHT and RHD. METHODS: This single-center prospective study was performed in a seven-bed teaching hospital intensive care unit (ICU). PHT and RHD criteria were compared by HHUD and CUD. Additional PHT criteria and right ventricle (RV) systolic and diastolic dysfunction criteria were also measured. RESULTS: Forty-six patients were included in the study. There was no significant difference between the imaging rates and mean values of the parameters measured by both devices. When the positivity rates for additional PHT parameters and RHD criteria were compared, there were no significant differences between the devices. In Bland-Altman's analysis, there was good agreement and there was no bias between the measurements of the two devices but left ventricular end-systolic eccentricity index (LVSEI), right atrium area (RAA), and pulmonary artery diameter (PAD). Ninety percent of the patients had PHT probability, of whom 43% had a low, 37% had intermediate and 10% had a high probability of PHT. Ninety-two percent of the patients had RHD and there was no significant difference between the devices in the diagnosis of RHD (p = .212). When RV systolic and diastolic dysfunction evaluations of the devices were compared according to the British Society of Echocardiography (BSE) criteria there was no significant difference between the devices' measurements in the evaluation of systolic and diastolic function. CONCLUSION: The imaging and measurement capabilities of the HHUDs for PHT and RHD parameters were similar to CUDs, and considering the inconsistent parameters, the HHUD can be useful in diagnosing these problems.

Successful management of HeartMate 3 in a patient with arrhythmogenic right ventricular cardiomyopathy.

The management of right heart failure during durable left ventricular assist device (LVAD) support remains an unsolved issue so far. We had a 44-year-old male patient who was diagnosed with arrhythmogenic right ventricular cardiomyopathy and received HeartMate 3 LVAD (Abbott, USA) implantation as a bridge-to-transplant indication. The pump speed was adjusted as low as 4500 rpm to avoid the left ventricular narrowing and interventricular septal leftward shift. Riociguat was administered to decrease the afterload of the right ventricle and increase the preload of the left ventricle, in addition to the combination of neurohormonal blockers. Frequent low-flow alarm events eventually disappeared after amlodipine administration, and he was successfully returned to work. We here present a unique management in a patient with right heart failure due to arrhythmogenic right ventricular cardiomyopathy during HeartMate 3 LVAD support.

The Pathophysiology(ies) of Heart Failure in Adults with Congenital Heart Disease.

There is a growing, aging population of adults with congenital heart disease (CHD) with an increasing incidence of heart failure. Unquestioning extrapolation of widely applicable definitions of heart failure and guidelines for managing heart failure in adults with acquired heart failure to adults with CHD can be problematic. A nuanced and flexible application of clinical judgment founded on a deep understanding of underlying pathophysiology is needed to most effectively apply the many recent advances in managing acquired heart failure to the care of adults with CHD.

Echocardiographic evaluation of right heart failure which might be associated with DNA damage response in SU5416-hypoxia induced pulmonary hypertension rat model.

Right heart failure is the leading cause of death in pulmonary hypertension (PH), and echocardiography is a commonly used tool for evaluating the risk hierarchy of PH. However, few studies have explored the dynamic changes in the structural and functional changes of the right heart during the process of PH. Previous studies have found that pulmonary circulation coupling right ventricular adaptation depends on the degree of pressure overload and other factors. In this study, we performed a time-dependent evaluation of right heart functional changes using transthoracic echocardiography in a SU5416 plus hypoxia (SuHx)-induced PH rat model. Rats were examined in 1-, 2-, 4-, and 6-week using right-heart catheterization, cardiac echocardiography, and harvested heart tissue. Our study found that echocardiographic measures of the right ventricle (RV) gradually worsened with the increase of right ventricular systolic pressure, and right heart hypofunction occurred at an earlier stage than pulmonary artery thickening during the development of PH. Furthermore, sarco-endoplasmic reticulum calcium ATPase 2 (SERCA2), a marker of myocardial damage, was highly expressed in week 2 of SuHx-induced PH and had higher levels of expression of γ-H2AX at all timepoints, as well as higher levels of DDR-related proteins p-ATM and p53/p-p53 and p21 in week 4 and week 6. Our study demonstrates that the structure and function of the RV begin to deteriorate with DNA damage and cellular senescence during the early stages of PH development.

[18 F] -FAPI-42 PET/CT assessment of Progressive right ventricle fibrosis under pressure overload.

BACKGROUND: Right heart failure (RHF) is a complication of pulmonary hypertension (PH) and increases the mortality independently of the underlying disease. However, the process of RHF development and progression is not fully understood. We aimed to develop effective approaches for early diagnosis and precise evaluation of RHF. METHODS: Right ventricle (RV) pressure overload was performed via pulmonary artery banding (PAB) surgery in Sprague-Dawley (SD) rats to induce RHF. Echocardiography, right heart catheterization, histological staining, fibroblast activation protein (FAP) immunofluorescence and 18 F-labelled FAP inhibitor-42 ([18 F] -FAPI-42) positron emission tomography/computed tomography (PET/CT) were performed at day 3, week 1, 2, 4 and 8 after PAB. RNA sequencing was performed to explore molecular alterations between PAB and sham group at week 2 and week 4 after PAB respectively. RESULTS: RV hemodynamic disorders were aggravated, and RV function was declined based on right heart catheterization and echocardiography at week 2, 4 and 8 after PAB. Progressive cardiac hypertrophy, fibrosis and capillary rarefaction could be observed in RV from 2 to 8 weeks after PAB. RNA sequencing indicated 80 upregulated genes and 43 downregulated genes in the RV at both week 2 and week 4 after PAB; Gene Ontology (GO) analysis revealed that fibrosis as the most significant biological process in the RV under pressure overload. Immunofluorescence indicated that FAP was upregulated in the RV from week 2 to week 8 after PAB; and [18 F] -FAPI-42 PET/CT revealed FAPI uptake was significantly higher in RV at week 2 and further increased at week 4 and 8 after PAB. CONCLUSION: RV function is progressively declined with fibrosis as the most prominent molecular change after pressure overload, and [18 F] -FAPI-42 PET/CT is as sensitive and accurate as histopathology in RV fibrosis evaluation.

Temporary Right Ventricular Assist Device Support for Acute Right Heart Failure: A Single-Center Experience.

INTRODUCTION: Severe right ventricular (RV) failure is associated with significant morbidity and mortality. Although right ventricular assist devices (RVADs) are increasingly used for refractory RV failure, there is limited data on their short- and long-term outcomes. Therefore, we undertook this study to better understand our experience with temporary RVADs. METHODS: We conducted a retrospective review of all RVADS performed from 2017 to 2021. Patients supported with surgical RVADs, the Protek Duo device, and the Impella RP device were included. Patients were stratified by the type of RVAD and by etiology of RV failure. Survival was assessed by the Kaplan-Meier method and multivariable Cox proportional hazards regression models. RESULTS: From 2017 to 2021, 42 patients underwent RVAD implantation: 32 with a Protek Duo, 6 with an Impella RP, and 4 with a surgical RVAD. Majority of patients were already supported with an alternate form of mechanical support. Most patients had impaired renal function, decreased hepatic function, and lactic acidosis at the time of cannulation. The median duration of RVAD support was 8.5 [5-19] d. Survival to decannulation was 68.4%, to discharge was 47.4%, and to 1-y was 40.2%. Multivariable analysis identified elevated total bilirubin levels to be associated with 30-d mortality while increased hemoglobin levels were protective. After RVAD cannulation, the median number of pressors and inotropes was lower (P < 0.01) and the lactic acidosis was less (P < 0.01). CONCLUSIONS: In conclusion, RVAD support is associated with lower lactate levels, and decreased number of vasoactive medications, but is associated with significant morbidity and mortality.

Right Heart Failure in the Intensive Care Unit: Etiology, Pathogenesis, Diagnosis, and Treatment.

Right heart (RH) failure carries a high rate of morbidity and mortality. Patients who present with RH failure often exhibit complex aberrant cardio-pulmonary physiology with varying presentations. The treatment of RH failure almost always requires care and management from an intensivist. Treatment options for RH failure patients continue to evolve rapidly with multiple options available, including different pharmacotherapies and mechanical circulatory support devices that target various components of the RH circulatory system. An understanding of the normal RH circulatory physiology, treatment, and support options for the RH failure patients is necessary for all intensivists to improve outcomes. The purpose of this review is to provide clinical guidance on the diagnosis and management of RH failure within the intensive care unit setting, and to highlight the different pathophysiological manifestations of RH failure, its hemodynamics, and treatment options available at the disposal of the intensivist.

Outcomes and Prognostic Factors of Pulmonary Hypertension Patients Undergoing Emergent Endotracheal Intubation.

Background: Emergent endotracheal intubations (ETI) in pulmonary hypertension (PH) patients are associated with increased mortality. Post-intubation interventions that could increase survivability in this population have not been explored. We evaluate early clinical characteristics and complications following emergent endotracheal intubation and seek predictors of adverse outcomes during this post-intubation period. Methods: Retrospective cohort analysis of adult patients with groups 1 and 3 PH who underwent emergent intubation between 2005-2021 in medical and liver transplant ICUs at a tertiary medical center. PH patients were compared to non-PH patients, matched by Charlson Comorbidity Index. Primary outcomes were 24-h post-intubation and inpatient mortalities. Various 24-h post-intubation secondary outcomes were compared between PH and control cohorts. Results: We identified 48 PH and 110 non-PH patients. Pulmonary hypertension was not associated with increased 24-h mortality (OR 1.32, 95%CI 0.35-4.94, P = .18), but was associated with inpatient mortality (OR 4.03, 95%CI 1.29-12.5, P = .016) after intubation. Within 24 h post-intubation, PH patients experienced more frequent acute kidney injury (43.5% vs. 19.8%, P = .006) and required higher norepinephrine dosing equivalents (6.90 [0.13-10.6] mcg/kg/min, vs. 0.20 [0.10-2.03] mcg/kg/min, P = .037). Additionally, the median P/F ratio (PaO2/FiO2) was lower in PH patients (96.3 [58.9-201] vs. 233 [146-346] in non-PH, P = .001). Finally, a post-intubation increase in PaCO2 was associated with mortality in the PH cohort (post-intubation change in PaCO2 +5.14 ± 16.1 in non-survivors vs. -18.7 ± 28.0 in survivors, P = .007). Conclusions: Pulmonary hypertension was associated with worse outcomes after emergent endotracheal intubation than similar patients without PH. More importantly, our data suggest that the first 24 hours following intubation in the PH group represent a particularly vulnerable period that may determine long-term outcomes. Early post-intubation interventions may be key to improving survival in this population.

Incidence and risk factors of late right heart failure in chronic mechanical circulatory support.

BACKGROUND: Late right heart failure (LRHF) is a common complication during long-term left ventricular assist device (LVAD) support. We aimed to identify risk factors for LRHF after LVAD implantation. METHODS: Patients undergoing primary LVAD implantation between 2006 and 2019 and surviving the perioperative period were included for this study (n = 261). Univariate Cox proportional hazards analysis was used to assess the association of clinical covariates and LRHF, stratified for device type. Variables with p < 0.10 entered the multivariable model. In a subset of patients with complete echocardiography or right catheterization data, this multivariable model was extended. Postoperative cardiopulmonary exercise test data were compared in patients with and without LRHF. RESULTS: Nineteen percentage of patients suffered from LRHF after a median of 12 months, of which 67% required hospitalization. A history of atrial fibrillation (AF) (HR: 2.06 [1.08-3.93], p = 0.029), a higher preoperative body mass index (BMI) (HR: 1.07 [1.01-1.13], p = 0.023), and intensive care unit (ICU) duration (HR: 1.03 [1.00-1.06], p = 0.025) were independent predictors of LHRF in the multivariable model. A significant relation between the severity of tricuspid regurgitation (TR) and LRHF (HR: 1.91 [1.13-3.21], p = 0.016) was found in patients with echocardiographic data. Patients with LRHF demonstrated a lower maximal workload and peak VO2 at 6 months postoperatively. CONCLUSION: A history of AF, BMI, and longer ICU stay may help identify patients at high risk for LRHF. Severity of TR was significantly related to LRHF in a subset of patients.

The combination of supervised and unsupervised learning based risk stratification and phenotyping in pulmonary arterial hypertension-a long-term retrospective multicenter trial.

BACKGROUND: Accurate risk stratification in pulmonary arterial hypertension (PAH), a devastating cardiopulmonary disease, is essential to guide successful therapy. Machine learning may improve risk management and harness clinical variability in PAH. METHODS: We conducted a long-term retrospective observational study (median follow-up: 67 months) including 183 PAH patients from three Austrian PAH expert centers. Clinical, cardiopulmonary function, laboratory, imaging, and hemodynamic parameters were assessed. Cox proportional hazard Elastic Net and partitioning around medoid clustering were applied to establish a multi-parameter PAH mortality risk signature and investigate PAH phenotypes. RESULTS: Seven parameters identified by Elastic Net modeling, namely age, six-minute walking distance, red blood cell distribution width, cardiac index, pulmonary vascular resistance, N-terminal pro-brain natriuretic peptide and right atrial area, constituted a highly predictive mortality risk signature (training cohort: concordance index = 0.82 [95%CI: 0.75 - 0.89], test cohort: 0.77 [0.66 - 0.88]). The Elastic Net signature demonstrated superior prognostic accuracy as compared with five established risk scores. The signature factors defined two clusters of PAH patients with distinct risk profiles. The high-risk/poor prognosis cluster was characterized by advanced age at diagnosis, poor cardiac output, increased red cell distribution width, higher pulmonary vascular resistance, and a poor six-minute walking test performance. CONCLUSION: Supervised and unsupervised learning algorithms such as Elastic Net regression and medoid clustering are powerful tools for automated mortality risk prediction and clinical phenotyping in PAH.

[2022 ESC/ERS guidelines on the diagnostics and treatment of pulmonary hypertension : A focussed review]. / 2022 ESC/ERS-Leitlinien zur Diagnostik und Therapie der pulmonalen Hypertonie : Ein fokussierter Überblick.

Pulmonary hypertension (PH) is a hemodynamic state that can be caused by a variety of underlying conditions. The pathophysiology is complex and can involve several organ systems, requiring a multidisciplinary approach to differential diagnostics and management. This review article provides a comprehensive overview of the most important changes in the updated 2022 European Society of Cardiology (ESC)/European Respiratory Society (ERS) guidelines on the diagnostics and treatment of pulmonary hypertension, as compared to the previous 2015 version. A special focus is on (i) updated hemodynamic definitions of PH, including general definition, precapillary vs. postcapillary PH, isolated postcapillary PH (IpcPH), combined postcapillary and precapillary PH (CpcPH), (ii) the clinical presentation and classification of PH, (iii) the diagnostic approach as well as (iv) specific aspects of pulmonary arterial hypertension (PAH, group 1), including risk assessment, treatment and PAH with comorbidities, PH associated with left heart (group 2) or lung disease (group 3), and chronic thromboembolic pulmonary hypertension (CTEPH, group 4). Regarding the latter, the specific diagnostic algorithm and the multimodal approach to treatment are presented. Finally, for each of the PH groups, clinically relevant aspects and innovations are briefly and concisely presented.

A novel metrics to predict right heart failure after left ventricular assist device implantation.

BACKGROUND: Right Heart Failure (RHF) is a severe complication that can occur after left ventricular assist device (LVAD) implantation, increasing early and late mortality. Although numerous RHF predictive scores have been developed, limited data exist on the external validation of these models. We therefore aimed at comparing existent risk score models and identifying predictors of severe RHF at our center. METHODS: In this retrospective, single-center analysis, clinical, biological and functional data were collected in patients implanted with a LVAD between 2011 and 2020. Early severe RHF was defined as the use of inotropes for ≥ 14 days, nitric oxide use for ≥ 48 h or unplanned right-sided circulatory support. Risk models were evaluated for the primary outcome of RHF or RVAD implantation by means of logistic regression and receiver operating characteristic curves. RESULTS: Among 92 patients implanted, 24 (26%) developed early severe RHF. The EUROMACS-RHF risk score performed the best in predicting RHF (C = 0.82-95% CI: 0.68-0.90), compared with the other scores (Michigan, CRITT). In addition, we developed a new model, based on four variables selected for the best reduced logistic model: the INTERMACS level, the number of inotropes used, the ratio of right atrial/pulmonary capillary wedge pressure and the ratio of right ventricle/left ventricle diameters by echocardiography. This model demonstrated significant discrimination of RHF (C = 0.9-95% CI: 0.76-0.96). CONCLUSION: Amongst available risk scores, EUROMACS-RHF performs best to predict the occurrence of RHF after LVAD implantation. Our model's performance compares well to the EUROMACS-RHF score, adding a more objective parameter to RV function evaluation.

Effects of balloon pulmonary angioplasty procedure on electrocardiographic parameters in patients with chronic thromboembolic pulmonary hypertension.

AIM: The aim of the present study was to evaluate the value of electrocardiography (ECG) in predicting postoperative hemodynamic improvement in patients with chronic thromboembolic pulmonary hypertension (CTEPH) undergoing balloon pulmonary angioplasty (BPA). MATERIAL AND METHODS: A total of 32 patients were included in the study. During ECG analysis, parameters that have been suggested to be related to right ventricular hypertrophy and/or dilatation were evaluated. The significance of the change in each parameter obtained at the pre-BPA visit and at the scheduled control visit 6 months after BPA was tested. In addition to ECG analysis, data related to right heart catheterization (RHC) and echocardiography, B-type natriuretic peptide (BNP) levels and World Health Organization (WHO) functional classifications of all patients were also recorded. The relationship between the amount of possible change in ECG parameters and the amount of possible change in hemodynamic parameters was investigated. RESULTS: The Daniel score, which has been suggested to have prognostic value in acute pulmonary embolism, decreased from 8.22 ± 5.68 to 6.56 ± 5.55 after the BPA procedure (p: 0.035). Among all parameters studied, only T wave height (V2 t) in V2 derivation changed significantly from -0.77 ± 2.39 to 1.27 ± 2.58 mm (p: 0.036). The amount of change in V2 T was found to significantly correlate with the amount of change in systolic right ventricular pressure, mean pulmonary artery pressure, pulmonary vascular resistance, and systemic vascular resistance. CONCLUSION: Postprocedural T wave changes in lead V2 might serve as a marker of hemodynamic improvement in patients with CTEPH who undergo BPA.

Intravenous prostacyclins for right ventricular failure following left ventricular assist device in paediatric heart failure.

Right ventricular failure after placement of left ventricular assist device in paediatric heart failure is associated with increased mortality. We report successful use of intravenous prostacyclin for right ventricular support and pulmonary hypertension after initiation of left ventricular assist device support. This suggests that intravenous prostacyclins may be an important therapy in right ventricular failure following ventricular assist device implantation.

Mitochondrial Integrity Is Critical in Right Heart Failure Development.

Molecular processes underlying right ventricular (RV) dysfunction (RVD) and right heart failure (RHF) need to be understood to develop tailored therapies for the abatement of mortality of a growing patient population. Today, the armament to combat RHF is poor, despite the advancing identification of pathomechanistic processes. Mitochondrial dysfunction implying diminished energy yield, the enhanced release of reactive oxygen species, and inefficient substrate metabolism emerges as a potentially significant cardiomyocyte subcellular protagonist in RHF development. Dependent on the course of the disease, mitochondrial biogenesis, substrate utilization, redox balance, and oxidative phosphorylation are affected. The objective of this review is to comprehensively analyze the current knowledge on mitochondrial dysregulation in preclinical and clinical RVD and RHF and to decipher the relationship between mitochondrial processes and the functional aspects of the right ventricle (RV).

Tricuspid Regurgitation and Right Heart Failure: The Role of Imaging in Defining Pathophysiology, Presentation, and Novel Management Strategies.

During the last few years, there has been a substantial shift in efforts to understand and manage secondary or functional tricuspid regurgitation (TR) given its prevalence, adverse prognostic impact, and symptom burden associated with progressive right heart failure. Understanding the pathophysiology of TR and right heart failure is crucial for determining the best treatment strategy and improving outcomes. In this article, we review the complex relationship between right heart structural and hemodynamic changes that drive the pathophysiology of secondary TR and discuss the role of multimodality imaging in the diagnosis, management, and determination of outcomes.