Burden of Heart Failure in Patients With Tricuspid Regurgitation and Effect of Transcatheter Repair on Different Subdimensions of Quality of Life.

BACKGROUND: Right-sided heart failure (HF) due to severe tricuspid regurgitation (TR) is associated with reduced quality of life (QoL). Here, we analyzed the impact of TR on specific QoL dimensions and the effect of transcatheter tricuspid valve intervention (TTVI) on individual QoL items. METHODS AND RESULTS: In this study, we included 174 patients with HF (49% women; median age, 79 years; 97% New York Heart Association ≥3) with baseline QoL assessment undergoing TTVI by transcatheter edge-to-edge-repair at our center between April 2016 and March 2022. QoL was assessed by the standardized Minnesota Living With HF Questionnaire. QoL change after TTVI and correlation to functional end points were analyzed. In addition, all QoL domains and the 21 individual items of the Minnesota Living With HF Questionnaire were analyzed. TTVI significantly reduced TR (TR ≥3: baseline 95%, 1-year-follow-up 7%; P<0.001). Total Minnesota Living with HF Questionnaire score improved from 37 (interquartile range, 26-50) points to 31 (interquartile range, 17-42) points (median follow-up-interval, 355 days; P<0.001). QoL improvement was associated with positive New York Heart Association class, 6-minute walking distance, and actigraphy changes (all P<0.05). The detailed analysis revealed that all items of the physical-related QoL dimension were impaired at baseline and strongly improved after TTVI. In contrast, the emotional and "social" Minnesota Living With HF Questionnaire dimensions were largely unaffected at baseline, yet specific items improved with TTVI. CONCLUSIONS: In this single-center study, we delineate the QoL-associated disease burden of TR and identify specific QoL items that improved after TTVI. Our findings support TTVI in patients with reduced QoL and may add to the development of specific tools assessing the functional status of an increasing patient population undergoing TTVI.

Paravalvular Leak Closure After Transcatheter Tricuspid Valve-in-Ring Implantation: A Case Report.

Transcatheter tricuspid valve intervention (TTVI) has emerged as a promising alternative for patients with severe tricuspid regurgitation who are deemed high-risk for surgery. With advancements in device design and delivery systems, TTVI has shown promising outcomes in reducing tricuspid regurgitation severity and improving symptoms in selected patients. Paravalvular leaks (PVLs) are one of the most common complications faced, which can significantly contribute to patients' morbidity and mortality. Percutaneous PVL closure represents a minimally invasive approach to address this issue, but its efficacy and safety in the context of transcatheter tricuspid valve-in-ring implantation require further elucidation. We describe the case of a 44-year-old lady with a history of rheumatic valve disease status post-tricuspid valve annuloplasty with an incomplete ring who presented to cardiology clinics with symptomatic torrential tricuspid regurgitation. Due to the high risk of surgical reintervention secondary to severe right ventricular (RV) failure, she was denied surgical intervention. Therefore, she underwent transcatheter tricuspid valve-in-ring (TVIR) implantation with a 26 mm MyVal (Meril Life Sciences Pvt Ltd., Vapi, GJ, IND), which was complicated by a residual severe tricuspid paravalvular regurgitation. The defect was subsequently closed by a dedicated Occlutech PVL device (Occlutech, Helsingborg, SWE) measuring 18 mm x 10 mm. Post which, the patient had trivial tricuspid regurgitation and significant improvement in signs and symptoms with subsequent follow-up.

Congestive Hepatopathy: A Review of the Literature.

Congestive hepatopathy (CH), stemming from compromised hepatic venous flow or heightened intrahepatic pressure, represents a significant consequence of cardiovascular conditions like congestive heart failure (CHF). This review of literature encapsulates the core aspects of this condition, characterized by hepatic congestion, cellular injury, and impaired liver function. Diagnostic challenges arise due to symptoms mirroring primary liver diseases. Management revolves around addressing the underlying cause and mitigating fluid retention. This review of literature provides a snapshot of CH's complexity, emphasizing its clinical implications and the need for comprehensive understanding in clinical practice.

Obstructive Sleep Apnea and Pulmonary Hypertension: A Chicken-and-Egg Relationship.

Obstructive sleep apnea (OSA) is characterized by repeated episodes of upper airway obstruction during sleep, and it is closely linked to several cardiovascular issues due to intermittent hypoxia, nocturnal hypoxemia, and disrupted sleep patterns. Pulmonary hypertension (PH), identified by elevated pulmonary arterial pressure, shares a complex interplay with OSA, contributing to cardiovascular complications and morbidity. The prevalence of OSA is alarmingly high, with studies indicating rates of 20-30% in males and 10-15% in females, escalating significantly with age and obesity. OSA's impact on cardiovascular health is profound, particularly in exacerbating conditions like systemic hypertension and heart failure. The pivotal role of hypoxemia increases intrathoracic pressure, inflammation, and autonomic nervous system dysregulation in this interplay, which all contribute to PH's pathogenesis. The prevalence of PH among OSA patients varies widely, with studies reporting rates from 15% to 80%, highlighting the variability in diagnostic criteria and methodologies. Conversely, OSA prevalence among PH patients also remains high, often exceeding 25%, stressing the need for careful screening and diagnosis. Treatment strategies like continuous positive airway pressure (CPAP) therapy show promise in mitigating PH progression in OSA patients. However, this review underscores the need for further research into long-term outcomes and the efficacy of these treatments. This review provides comprehensive insights into the epidemiology, pathophysiology, and treatment of the intricate interplay between OSA and PH, calling for integrated, personalized approaches in diagnosis and management. The future landscape of OSA and PH management hinges on continued research, technological advancements, and a holistic approach to improving patient outcomes.

Escalating Oral Treprostinil Dose With Intravenous Treprostinil Bridging Therapy.

Oral treprostinil, approved for the treatment of pulmonary arterial hypertension, remains an attractive option in combination with other medications to delay disease progression and improve exercise capacity. However, patients are often challenged with the ability to overcome adverse effects as outpatients and reach effective doses in a timely manner. We describe a case of a 47-year-old female on oral treprostinil who presented to the clinic with worsening symptoms of disease, necessitating higher dosing. This patient was previously uptitrated outpatient with oral treprostinil, which had allowed her to remain stable for years. Once uptitrated with additional intravenous therapy, the oral treprostinil dose was gradually further increased to the new goal dosage, resulting in improvements in symptoms and right ventricular function. This case highlights the versatility of dose optimization of oral treprostinil with rapid bridging through intravenous therapy.

An Unusual Etiology of Severe Right Heart Failure Deserving of Wider Recognition.

A previously healthy 31-year-old man presented with worsening shortness of breath and a petechial rash. Echocardiography showed severe right-sided heart failure with midsystolic notching of the antegrade right ventricular outflow Doppler envelope suggesting pulmonary hypertension. An extensive work-up revealed scurvy, with a dramatic resolution of symptoms shortly after vitamin C supplementation.

Pulmonary Tumor Thrombotic Microangiopathy Caused by Esophageal Adenocarcinoma: A Case Report.

Pulmonary tumor thrombotic microangiopathy (PTTM ) is a rare condition of uncertain incidence given its likely underdiagnosis. PTTM has been described most frequently in association with gastric adenocarcinoma, but other primary malignancies have been identified. The prognosis of PTTM is very poor, and patients often die within days or weeks of diagnosis. There are, however, several medications currently being used with unknown therapeutic benefits. The case presented below describes a patient with PTTM and esophageal adenocarcinoma, which may be the first report of its kind. One other case of esophageal cancer associated with PTTM was found in the literature review, but it is of squamous cell carcinoma histology. Herein, we report a case of a male with rapidly progressive pulmonary hypertension and right heart failure who, in the course of treatment/evaluation, was found to have esophageal adenocarcinoma. While early diagnosis may not alter the course of the disease, antemortem diagnosis may identify better therapeutic options and better inform patients of their prognosis, allowing them to maintain autonomy in their medical decisions.

The Hypoxic Tricuspid: A Flail Tricuspid Valve With Patent Foramen Ovale.

Etiologies of tricuspid regurgitation are often explored in patients with symptoms of right-sided heart failure. Blunt chest trauma is the major cause of traumatic tricuspid valve regurgitation (TTVR), a secondary type of tricuspid regurgitation. It is a rare condition; however, it may lead to severe consequences if not treated in a timely manner. TTVR should be considered in a patient presenting with chest trauma. In this case, we report a case of a young male who presented after a motor vehicle accident with secondary tricuspid valve regurgitation due to blunt chest trauma as well as a patent foramen ovale.

Initial Triple Combination Therapy Including Intravenous Prostaglandin I2 for the Treatment of Patients with Severe Pulmonary Arterial Hypertension.

Upfront combination therapy including intravenous prostaglandin I2 (PGI2-IV) is recognized as the most appropriate treatment for patients with severe pulmonary arterial hypertension (PAH). This retrospective study aimed to determine reasons why this therapy is not used for some patients with severe PAH and describe the hemodynamic and clinical prognoses of patients receiving initial combination treatment with (PGI2-IV+) or without (PGI2-IV-) PGI2-IV.Data for patients with severe PAH (World Health Organization Functional Class III/IV and mean pulmonary arterial pressure [mPAP] ≥ 40 mmHg) were extracted from the Japan Pulmonary Hypertension Registry. Overall, 73 patients were included (PGI2-IV + n = 17; PGI2-IV- n = 56). The PGI2-IV+ cohort was younger than the PGI2-IV- cohort (33.8 ± 10.6 versus 52.6 ± 18.2 years) and had higher mPAP (58.1 ± 12.9 versus 51.8 ± 9.0 mmHg), greater prevalence of idiopathic PAH (88% versus 32%), and less prevalence of connective tissue disease-associated PAH (0% versus 29%). Hemodynamic measures, including mPAP, showed improvement in both cohorts (post-treatment median [interquartile range] 38.5 [17.0-40.0] for the PGI2-IV + cohort and 33.0 [25.0-43.0] mmHg for the PGI2-IV - cohort). Deaths (8/56) and lung transplantation (1/56) occurred only in the PGI2-IV - cohort.These Japanese registry data indicate that older age, lower mPAP, and non-idiopathic PAH may influence clinicians against using upfront combination therapy including PGI2-IV for patients with severe PAH. Early combination therapy including PGI2-IV was associated with improved hemodynamics from baseline, but interpretation is limited by the small sample size.

Migrated Inferior Vena Cava (IVC) Filter Presenting as Tricuspid Valve Mass, Right-Sided Heart Failure, and Parodoxical Emboli.

A 58-year-old male with an unknown medical history presented with acute encephalopathy, receptive aphasia, and hypertensive emergency. The patient did not have any family members from whom a collateral history could be obtained. He underwent X-rays of the abdomen and bilateral humeri/femurs to check for foreign bodies. He was found to have right femoral open reduction and internal fixation with retained screw fragments. He was diagnosed with ischemic stroke on MRI. Transthoracic echocardiogram (TTE) revealed right-sided heart failure and a tricuspid valve mass as well as right to left shunting. This raised concern for large atrial septal defect (ASD) with paradoxical embolization from tricuspid valve mass. Transesophageal echocardiogram (TEE) redemonstrated large ASD. Concern was raised for the ASD closure device as the cause of this "tricuspid mass." Due to history of orthopedic procedure, it was hypothesized that the patient had an IVC filter placed in the setting of pulmonary embolism (PE) prior to an orthopedic procedure. The tricuspid valve was visualized under fluoroscopy and was confirmed to be a migrated IVC filter. He was taken to the operating room (OR) for cardiac surgery for the removal of the IVC filter and repair of ASD. Surprisingly, no ASD was found.

Jiedu Quyu Decoction mitigates monocrotaline-induced right-sided heart failure associated with pulmonary artery hypertension by inhibiting NLRP3 inflammasome in rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Right-side heart failure could accelerate mortality in patients of pulmonary hypertension, Jiedu Quyu Decoction (JDQYF) was used to manage pulmonary hypertension, but its right-sided heart protective effect associated with pulmonary artery hypertension is still unclear. AIM OF THE STUDY: Here, we evaluated the therapeutic effect of JDQYF on monocrotaline-induced right-sided heart failure associated with pulmonary arterial hypertension in Sprague-Dawley (SD) rats and investigated the potential mechanism of action. MATERIALS AND METHODS: The main chemical components of JDQYF were detected and analyzed using ultra-high-performance liquid chromatography quadrupole time-of-flight mass spectrometry. The effects of JDQYF were investigated using a rat model of monocrotaline-induced right-sided heart failure associated with pulmonary arterial hypertension. We assessed the morphology of cardiac tissue using histopathology and the structure and function of the right heart using echocardiography. The biomarkers of heart failure, atrial natriuretic peptide and B-type natriuretic peptide, as well as serum pro-inflammatory markers, interleukin (IL)-1ß, and IL-18, were measured by enzyme-linked immunosorbent assay (ELISA). Furthermore, the mRNA and protein expression levels of NLRP3 (NOD-, LRR-, and pyrin domain-containing 3), capase-1, IL-1ß, and IL-18 in the right heart tissue were examined by real-time quantitative reverse transcription PCR and western blotting. RESULTS: JDQYF improved ventricular function, alleviated pathological lesions in the right cardiac tissue, reduced the expression levels of biomarkers of heart failure and serum pro-inflammatory factors (IL-1ß and IL-18), and downregulated the mRNA and protein expression levels of NLRP3, caspase-1, IL-1ß, and IL-18 in the right cardiac tissue. CONCLUSIONS: JDQYF possesses cardioprotective effect against right heart failure induced by pulmonary arterial hypertension, possibly owing to reduction of cardiac inflammation through the inhibition of NLRP3 inflammasome activation.

Initial clinical experience of intravenous tolvaptan sodium phosphate in patients with congestive heart failure.

Tolvaptan sodium phosphate (Samtas®; Otsuka Pharmaceutical, Tokyo, Japan) is a newly available intravenous aquaretic diuretic (commercially available from May 2022), which acts as an arginine vasopressin V2 receptor antagonist. Thus far, optimal patient selection as well as safety and efficacy in real-world practice remain unknown. We experienced two patients with congestive heart failure treated with tolvaptan sodium phosphate. In one patient with right-sided heart failure, oral tolvaptan was converted to intravenous tolvaptan sodium phosphate, and another one with right and left-sided heart failure and impaired swallowing function received intravenous tolvaptan sodium phosphate on a de novo basis. Following the initiation of tolvaptan sodium phosphate, their congestive symptoms ameliorated immediately without any complications. Tolvaptan sodium phosphate may be safe and effective in real-world practice, although further studies are warranted to establish optimal patient selection and clinical management. Learning objective: We report here an initial experience of newly-introduced intravenous tolvaptan sodium phosphate in real-world practice. The novel medication might be particularly suitable for those with severe thirst, congestive gut edema, or requiring rapid amelioration of systemic/pulmonary congestion, although further accumulating experiences are warranted to establish optimal therapeutic strategy.

Efficacy of levosimendan infusion in patients undergoing a left ventricular assist device implant in a propensity score matched analysis of the EUROMACS registry-the Euro LEVO-LVAD study.

OBJECTIVES: Early right-sided heart failure (RHF) was seen in 22% of recipients of a left ventricular assist device (LVAD) in the European Registry for Patients with Mechanical Circulatory Support (EUROMACS). However, the optimal treatment of post-LVAD RHF is not well known. Levosimendan has proven to be effective in patients with cardiogenic shock and in those with end-stage heart failure. We sought to evaluate the efficacy of levosimendan on post-LVAD RHF and 30-day and 1-year mortality. METHODS: The EUROMACS Registry was used to identify adults with mainstream continuous-flow LVAD implants who were treated with preoperative levosimendan compared to a propensity matched control cohort. RESULTS: In total, 3661 patients received mainstream LVAD, of which 399 (11%) were treated with levosimendan pre-LVAD. Patients given levosimendan had a higher EUROMACS RHF score [4 (2- 5.5) vs 2 (2- 4); P < 0.001], received more right ventricular assist devices (RVAD) [32 (8%) vs 178 (5.5%); P = 0.038] and stayed longer in the intensive care unit post-LVAD implant [19 (8-35) vs 11(5-25); P < 0.001]. Yet, there was no significant difference in the rate of RHF, 30-day, or 1-year mortality. Also, in the matched cohort (357 patients taking levosimendan compared to an average of 622 controls across 20 imputations), we found no evidence for a difference in postoperative severe RHF, RVAD implant rate, length of stay in the intensive care unit or 30-day and 1-year mortality. CONCLUSIONS: In this analysis of the EUROMACS registry, we found no evidence for an association between levosimendan and early RHF or death, albeit patients taking levosimendan had much higher risk profiles. For a definitive conclusion, a multicentre, randomized study is warranted.

Shear Wave Dispersion Slope of the Liver Can Predict Adverse Outcomes in Patients with Pulmonary Hypertension.

Pulmonary hypertension (PH) often causes right-sided heart failure (HF), inducing organ damage. Shear wave elastography (SWE) is a novel ultrasound technique for characterizing tissue. Some studies have reported that shear wave dispersion slope (SWDS) enables the assessment of early hepatic damage in HF. This study aimed to evaluate the prognostic impact of SWDS in patients with PH.This single-center cohort study enrolled 36 patients with PH who underwent SWE at Okayama University Hospital between March 2018 and April 2021. Patients were divided into 2 groups on the basis of the median value of SWDS: low SWDS group (SWDS < 12.4 m/second/kHz, n = 18) and high SWDS group (SWDS ≥ 12.4 m/second/kHz, n = 18). The primary endpoint was the complex of all-cause death or hospitalization for HF. During the follow-up of 391 ± 288 days, all-cause death or hospitalization for HF occurred in 8 patients. One patient died in the low SWDS group. Three patients died and 4 patients were hospitalized for HF in the high group. Kaplan-Meier analysis revealed that the event-free survival rate was significantly worse in the high SWDS group than in the low SWDS group (log-rank, P = 0.01). In univariate Cox proportional hazards analysis, high SWDS was associated with the events (hazard ratio 10.8; 95% confidence interval 1.89-202, P = 0.005).An elevated SWDS was associated with a high rate of events in patients with PH. SWDS has the potential to predict adverse outcomes in patients with PH.

An Unusual Presentation of Eisenmenger Syndrome in a Middle-Aged Woman Without Known Cardiac History.

Eisenmenger syndrome (ES) is a severe cardiac complication that arises from an untreated congenital cardiac defect, leading to the reversal of shunt flow, pulmonary hypertension, and cyanosis. This uncommon complication most frequently arises from small ventricular septal defects that are undiagnosed due to a lack of symptoms. However, it may arise from the reversal of any left-to-right cardiac shunt. In the following report, we present a case of acute-onset ES in a 52-year-old woman with no past cardiac history. The patient presented to the emergency department with a clinical presentation consistent with likely pulmonary embolism; however, after extensive work-up, this etiology of respiratory failure was deemed incorrect. After rapid respiratory decline requiring mechanical ventilation, the medical team performed two transthoracic echocardiograms (one with agitated saline study), one transesophageal echocardiogram, and a right cardiac catheterization on the patient. This work-up revealed pulmonary hypertension, right heart failure, and an atrial septal defect. Given these findings, the work-up was suggestive of ES secondary to an atrial septal defect shunt reversal. Because of the complexity of treatment, the patient was transferred via air to a university tertiary medical institution for extracorporeal membrane oxygenation along with other advanced treatments. This case provides a framework for the clinical presentation and treatment of this life-threatening disease. We hope that this information will help providers understand the clinical presentation, work-up, treatment, and prognosis of patients with Eisenmenger syndrome.

Metabolomic Signatures Associated With Pulmonary Arterial Hypertension Outcomes.

BACKGROUND: Pulmonary arterial hypertension (PAH) is a complex disease characterized by progressive right ventricular (RV) failure leading to significant morbidity and mortality. Investigating metabolic features and pathways associated with RV dilation, mortality, and measures of disease severity can provide insight into molecular mechanisms, identify subphenotypes, and suggest potential therapeutic targets. METHODS: We collected data from a prospective cohort of PAH participants and performed untargeted metabolomic profiling on 1045 metabolites from circulating blood. Analyses were intended to identify metabolomic differences across a range of common metrics in PAH (eg, dilated versus nondilated RV). Partial least squares discriminant analysis was first applied to assess the distinguishability of relevant outcomes. Significantly altered metabolites were then identified using linear regression, and Cox regression models (as appropriate for the specific outcome) with adjustments for age, sex, body mass index, and PAH cause. Models exploring RV maladaptation were further adjusted for pulmonary vascular resistance. Pathway enrichment analysis was performed to identify significantly dysregulated processes. RESULTS: A total of 117 participants with PAH were included. Partial least squares discriminant analysis showed cluster differentiation between participants with dilated versus nondilated RVs, survivors versus nonsurvivors, and across a range of NT-proBNP (N-terminal pro-B-type natriuretic peptide) levels, REVEAL 2.0 composite scores, and 6-minute-walk distances. Polyamine and histidine pathways were associated with differences in RV dilation, mortality, NT-proBNP, REVEAL score, and 6-minute walk distance. Acylcarnitine pathways were associated with NT-proBNP, REVEAL score, and 6-minute walk distance. Sphingomyelin pathways were associated with RV dilation and NT-proBNP after adjustment for pulmonary vascular resistance. CONCLUSIONS: Distinct plasma metabolomic profiles are associated with RV dilation, mortality, and measures of disease severity in PAH. Polyamine, histidine, and sphingomyelin metabolic pathways represent promising candidates for identifying patients at high risk for poor outcomes and investigation into their roles as markers or mediators of disease progression and RV adaptation.

Chronic Expanding Haematoma Causing Stenosis of the Right Ventricular Outflow Tract and Pulmonary Hypertension.

A chronic expanding haematoma (CEH) is an encapsulated mass that gradually increases in size from repeated internal bleeding and neovascularization. We herein report a 69-year-old man who was admitted with dyspnoea on exertion after undergoing thymic carcinoma resection 17 years ago. Chest computed tomography showed a heterogeneous mass in the anterior mediastinum and compression of the right ventricle, and pulmonary artery. Right cardiac catheterisation revealed pulmonary hypertension that was relieved after resection of the diagnosed CEH mass. This report highlights the mechanism underlying anterior mediastinal CEH-induced stenotic compression of the right ventricle-pulmonary artery outflow and subsequent pulmonary hypertension.

Biomarkers in Pulmonary Arterial Hypertension.

Pulmonary arterial hypertension (PAH) is a severe medical condition characterized by elevated pulmonary vascular resistance (PVR), right ventricular (RV) failure, and death in the absence of appropriate treatment. The progression and prognosis are strictly related to the etiology, biochemical parameters, and treatment response. The gold-standard test remains right-sided heart catheterization, but dynamic monitoring of systolic pressure in the pulmonary artery is performed using echocardiography. However, simple and easily accessible non-invasive assays are also required in order to monitor this pathology. In addition, research in this area is in continuous development. In recent years, more and more biomarkers have been studied and included in clinical guidelines. These biomarkers can be categorized based on their associations with inflammation, endothelial cell dysfunction, cardiac fibrosis, oxidative stress, and metabolic disorders. Moreover, biomarkers can be easily detected in blood and urine and correlated with disease severity, playing an important role in diagnosis, prognosis, and disease progression.