Challenges and Insights: Severe Acute Right Ventricular Dysfunction in Pulmonary Hypertension.

Pulmonary hypertension (PH) is rarely a cause of syncope. We highlight an unusual presentation of pulmonary hypertension where management was a veritable challenge. We present a case report of a 35-year-old female with a history of stage 2 hypertension, polycystic ovarian syndrome, and obesity who presented to the hospital with a six-month history of progressive shortness of breath, lower extremity swelling, and recurrent syncope. Further evaluation with transthoracic echocardiography showed features consistent with severe pulmonary hypertension. This untreated severe pulmonary hypertension culminated in cardiogenic shock due to right ventricular (RV) failure. Successful care in this patient population entails preventing the acute downward spiral of decompensated right ventricular failure.

A review regarding the article `Right heart catheterization in idiopathic pulmonary hypertension: An all-inclusive necessity'.

Right heart catheterization (RHC) stands as a unique tool for both diagnosing and managing a broad spectrum of cardiovascular diseases. Though its origins trace back to the 18th century, the most substantial progress was achieved in the 20th century. The focus of this review is on pulmonary hypertension (PH), where RHC is recognized as the diagnostic gold standard. Parameters derived from this procedure are crucial for classifying PH into various subgroups, assessing the risk of adverse events or mortality, and informing treatment strategies. The European Society of Cardiology guidelines define PH as an increase in mean pulmonary artery pressure (PAPm) greater than 25 mmHg. The differentiation between pre- and post-capillary PH is based on the levels of pulmonary artery wedge pressure (PAWP). Furthermore, right atrial pressure (RAP), cardiac index (CI), and mixed venous oxygen saturation (SvO2) are the sole parameters recommended for prognostic assessment, specifically in patients with pulmonary arterial hypertension (PAH). Patients presenting with RAP exceeding 14 mmHg, CI less than 2.0 L/min/m2, and SvO2 below 60% are considered to be at a high risk (greater than 10%) of death within the subsequent year. A primary goal in the management of PAH is the early diagnosis to facilitate the swift initiation of treatment. This aims to minimize symptom burden, optimize the patient's biochemical, hemodynamic, and functional profile, and curtail adverse events. To achieve these objectives, clinicians must remain informed about emerging risk factors and be familiar with the revised hemodynamic definition for PAH.

Blood Cholesterol and Triglycerides Associate with Right Ventricular Function in Pulmonary Hypertension.

Background: Blood lipids are dysregulated in pulmonary hypertension (PH). Lower high-density lipoproteins cholesterol (HDL-C) and low-density lipoproteins cholesterol (LDL-C) are associated with disease severity and death in PH. Right ventricle (RV) dysfunction and failure are the major determinants of morbidity and mortality in PH. This study aims to test the hypothesis that dyslipidemia is associated with RV dysfunction in PH. Methods: We enrolled healthy control subjects (n=12) and individuals with PH (n=30) (age: 18-65 years old). Clinical characteristics, echocardiogram, 2-[18F] fluoro-2-deoxy-D-glucose positron emission tomography (PET) scan, blood lipids, including total cholesterol (TC), triglycerides (TG), lipoproteins (LDL-C and HDL-C), and N-terminal pro-B type Natriuretic Peptide (NT-proBNP) were determined. Results: Individuals with PH had lower HDL-C [PH, 41±12; control, 56±16 mg/dL, p<0.01] and higher TG to HDL-C ratio [PH, 3.6±3.1; control, 2.2±2.2, p<0.01] as compared to controls. TC, TG, and LDL-C were similar between PH and controls. Lower TC and TG were associated with worse RV function measured by RV strain (R=-0.43, p=0.02 and R=-0.37, p=0.05 respectively), RV fractional area change (R=0.51, p<0.01 and R=0.48, p<0.01 respectively), RV end-systolic area (R=-0.63, p<0.001 and R=-0.48, p<0.01 respectively), RV end-diastolic area: R=-0.58, p<0.001 and R=-0.41, p=0.03 respectively), and RV glucose uptake by PET (R=-0.46, p=0.01 and R=-0.30, p=0.10 respectively). NT-proBNP was negatively correlated with TC (R=-0.61, p=0.01) and TG (R=-0.62, p<0.02) in PH. Conclusion: These findings confirm dyslipidemia is associated with worse right ventricular function in PH.

Atypical Adult-Onset Still's Disease Presenting With Seizures and Myocarditis Complicated by Macrophage Activation Syndrome.

Adult-onset Still's disease (AOSD) is a rare multi-systemic inflammatory disorder characterized by high spiking fevers, nonpruritic, salmon-colored rash, and severe polyarthralgia. Laboratory features typically include elevation in white blood cells, liver enzymes, and ferritin. Central nervous system and cardiac involvements, particularly myocarditis, are rare. Macrophage activation syndrome (MAS) is a well-described complication of AOSD, leading to a high mortality rate. Herein, we describe a case of AOSD complicated by MAS in a 32-year-old male presenting with atypical clinical manifestations, including recurrent seizures, scaly, pruritic, and hyperpigmented rash, and right heart failure due to lymphocytic myocarditis. The patient exhibited a delayed onset of fever, leukocytosis, and transaminitis that initially deterred eligibility for Yamaguchi criteria for AOSD. Bone marrow and lymph node biopsies did not show malignancy, infection, or hemophagocytosis. However, soluble interleukin-2 receptor alpha or soluble CD-25 was elevated. The patient experienced significant improvement on combination therapy of anakinra, methotrexate, and stress-dose steroids. HScore was later indicative of a high probability for MAS. Outpatient management involved prednisone, cyclosporine, and canakinumab for MAS. Seizure and myocarditis are possible presenting features of atypical AOSD. Early recognition of non-criteria AOSD and MAS and prompt initiation of therapy may prevent mortality.

The Role of Artificial Intelligence and Machine Learning in the Prediction of Right Heart Failure after Left Ventricular Assist Device Implantation: A Comprehensive Review.

One of the most challenging and prevalent side effects of LVAD implantation is that of right heart failure (RHF) that may develop afterwards. The purpose of this study is to review and highlight recent advances in the uses of AI in evaluating RHF after LVAD implantation. The available literature was scanned using certain key words (artificial intelligence, machine learning, left ventricular assist device, prediction of right heart failure after LVAD) was scanned within Pubmed, Web of Science, and Google Scholar databases. Conventional risk scoring systems were also summarized, with their pros and cons being included in the results section of this study in order to provide a useful contrast with AI-based models. There are certain interesting and innovative ML approaches towards RHF prediction among the studies reviewed as well as more straightforward approaches that identified certain important predictive clinical parameters. Despite their accomplishments, the resulting AUC scores were far from ideal for these methods to be considered fully sufficient. The reasons for this include the low number of studies, standardized data availability, and lack of prospective studies. Another topic briefly discussed in this study is that relating to the ethical and legal considerations of using AI-based systems in healthcare. In the end, we believe that it would be beneficial for clinicians to not ignore these developments despite the current research indicating more time is needed for AI-based prediction models to achieve a better performance.

Postoperative Pulmonary Artery Pulsatility Index Improves Prediction of Right Ventricular Failure After Left Ventricular Assist Device Implantation.

OBJECTIVES: This study evaluated whether the postoperative pulmonary artery pulsatility index (PAPi) is associated with postoperative right ventricular dysfunction after durable left ventricular assist device (LVAD) implantation. DESIGN: Single-center retrospective observational cohort study. SETTING: The University of Kansas Medical Center, a tertiary-care academic medical center. PARTICIPANTS: Sixty-seven adult patients who underwent durable LVAD implantation between 2017 and 2019. INTERVENTIONS: All patients underwent open cardiac surgery with cardiopulmonary bypass under general anesthesia with pulmonary artery catheter insertion. MEASUREMENTS AND MAIN RESULTS: Clinical and hemodynamic data were collected before and after surgery. The Michigan right ventricular failure risk score and the European Registry for Patients with Mechanical Circulatory Support score were calculated for each patient. The primary outcome was right ventricular failure, defined as a composite of right ventricular mechanical circulatory support, inhaled pulmonary vasodilator therapy for 48 hours or greater, or inotrope use for 14 days or greater or at discharge. Thirty percent of this cohort (n = 20) met the primary outcome. Preoperative transpulmonary gradient (odds ratio [OR] 1.15, 95% CI 1.02-1.28), cardiac index (OR 0.83, 95% CI 0.71-0.98), and postoperative PAPi (OR 0.85, 95% CI 0.75-0.97) were the only hemodynamic variables associated with the primary outcome. The addition of postoperative PAPi was associated with improvement in the predictive model performance of the Michigan score (area under the receiver operating characteristic curve 0.73 v 0.56, p = 0.03). An optimal cutoff point for postoperative PAPi of 1.56 was found. CONCLUSIONS: The inclusion of postoperative PAPi offers more robust predictive power for right ventricular failure in patients undergoing durable LVAD implantation, compared with the use of existing risk scores alone.

Right Ventricle Response to Major Lung Resection (the RIVER Study).

Backgrounds: Major lung resection is associated with high postoperative morbidity and mortality, especially due to cardiorespiratory complications. Right ventricle (RV) ejection, pulmonary artery (PA) pressure, and tone are tightly coupled. Since the RV is exquisitely sensitive to changes in afterload, an acute increase in RV outflow resistance (i.e., acute pulmonary embolism [PE]) will cause acute RV dilatation and, a reduction of left ventricle compliance too, rapidly spiraling to acute cardiogenic shock and death. We investigated the changing in RV performance after major lung resection. Materials and Methods: We carried out transthoracic echocardiography (TTE) aiming at searching for the incidence of early RV systolic dysfunction (defined as tricuspid annulus plane systolic excursion [TAPSE] <17 cm, S'-tissue Doppler imaging <10 cm/s) and estimate the RV-PA coupling by the TAPSE/pulmonary artery pressures (PAPs) ratio after major lung resection. The TTE has been performed before and immediately after surgery. Results: After the end of the operation the echocardiographic parameters of the RV function worsened. TAPSE decreased from 24 (21 ÷ 28) to 18 (16 ÷ 22) mm (P = 0.015) and PAPs increased from 26 (25 ÷ 30) to 30 (25 ÷ 39) mmHg (P = 0.013). TAPSE/PAPs ratio decreased from 0.85 (0.80 ÷ 0.90) to 0.64 (0.54 ÷ 0.79) mm/mmHg (P = 0.002). Conclusions: In line with previous reports, after major lung resection the increase in afterload reduces the RV function, but the impairment remains clinically not relevant. The different clinical picture of an acute cor pulmonale due to PE implies that the pathogenesis of cardiac failure involves more pathways than the mere mechanic occlusion of the blood flow.

Fallo agudo de ventrículo derecho debido a microangiopatía / Right ventricle failure secondary to thrombotic microangiopathy

La microangiopatía trombótica tumoral pulmonar es una enfermedad infrecuente con un diagnóstico de elevada complejidad,que requiere una alta sospecha clínica. La detección precoz es importante debido al mal pronóstico en estadios avanzados.Presentamos el caso de un varón de 39 años ingresado en el hospital para estudio por tos, disnea progresiva, hipertensiónpulmonar y adenopatías abdominales. Durante su ingreso sufrió parada cardiorrespiratoria que no respondió a maniobrasde reanimación cardiopulmonar avanzadas. El examen post mortem mostró hallazgos compatibles con microangiopatíatrombótica tumoral pulmonar secundaria a adenocarcinoma gástrico en estadio avanzado.(AU)

Pulmonary tumour thrombotic microangiopathy is an infrequent disease with a high complex diagnosis that requires highclinical suspicion. Early detection is important because of the poor prognosis in advanced stages. We introduce a case of a39-year-old male admitted in hospital with symptoms of cough, progressively worsening dyspnea, pulmonary hypertensionand abdominal adenopathies. During admission he suffered a cardiac arrest with no response to advanced cardiopulmonaryresuscitation manoeuvres. Post mortem study revealed a pulmonary tumoral thrombotic microangiopathy secondary to gastricadenocarcinoma in advanced stage.(AU)

Redo heart transplantation in a high-risk patient due to severe aortic regurgitation and accompanying right ventricular failure after LVAD implantation and temporary RVAD support.

BACKGROUND: We report a 62-year-old patient who received redo-orthotopic heart transplantation due to worsening severe aortic regurgitation after 19 months of continuous flow left ventricular assist device  (LVAD) (cf-LVAD) and temporary right ventricular assist device (RVAD) support for 1 month. CASE REPORT: The patient received a heartware LVAD (heartware ventricular assist device) and annuloplasty of the tricuspid valve due to end-stage heart failure (as a consequence of dilated cardiomyopathy) and severe tricuspid regurgitation in addition to right-sided extracorporeal membrane oxygenation (ECMO) implantation. Postoperatively due to the inability to wean the implanted ECMO, a temporary RVAD was implanted after which the patient's condition improved so that it had been explanted later and the patient was discharged after 9 months. In immediate postoperative echo, minimal aortic regurgitation was noted but in the follow-up transthoracic echocardiograms, there was a gradual increase in the severity of aortic regurgitation with worsening both right and left ventricular functions. Transcatheter aortic valve implantation was not an option due to unfavorable anatomical issues. That's why the patient was listed for urgent heart transplantation, performed 19 months after the LVAD implantation. The postoperative course was complicated due to acute renal failure. After recompensation, dialysis, and intensive physiotherapy, the patient could be discharged home after 3 months. CONCLUSION: Severe aortic regurgitation is a recognizable complication after cf-LVAD implantation which in our case was managed successfully with orthotopic heart transplantation in this high-risk patient.

Novel p38 Mitogen-Activated Protein Kinase Inhibitor Reverses Hypoxia-Induced Pulmonary Arterial Hypertension in Rats.

Mitogen-activated protein kinase (MAPK) signaling is strongly implicated in cardiovascular remodeling in pulmonary hypertension (PH) and right ventricle (RV) failure. The effects of a newly designed p38 inhibitor, LASSBio-1824, were investigated in experimentally induced PH. Male Wistar rats were exposed to hypoxia and SU5416 (SuHx), and normoxic rats were used as controls. Oral treatment was performed for 14 days with either vehicle or LASSBio-1824 (50 mg/kg). Pulmonary vascular resistance and RV structure and function were assessed by echocardiography and catheterization. Histological, immunohistochemical and Western blot analysis of lung and RV were performed to investigate cardiovascular remodeling and inflammation. Treatment with LASSBio-1824 normalized vascular resistance by attenuating vessel muscularization and endothelial dysfunction. In the heart, treatment decreased RV systolic pressure, hypertrophy and collagen content, improving cardiac function. Protein content of TNF-α, iNOS, phosphorylated p38 and caspase-3 were reduced both in lung vessels and RV tissues after treatment and a reduced activation of transcription factor c-fos was found in cardiomyocytes of treated SuHx rats. Therefore, LASSBio-1824 represents a potential candidate for remodeling-targeted treatment of PH.

Porto-pulmonary arterial hypertension: Translation of pathophysiological concepts to the bedside.

Porto-pulmonary arterial hypertension (PoPAH) is a form of pulmonary arterial hypertension (PAH) that affects patients with cirrhosis, and - to a lesser extent - patients with non-cirrhotic liver diseases. Compared with other forms of PAH, PoPAH is more prevalent in male, in older subjects, and is characterized by lower mean pulmonary arterial pressure (mPAP) and lower pulmonary vascular resistance (PVR) with higher cardiac output. Despite more favorable hemodynamics and functional class, patients with PoPAH have a significantly worse survival than patients with other forms of PAH, likely because of liver-related events and therapeutic barriers to PAH-specific therapy. Furthermore, here cardiopulmonary and hepatic complications may affect treatment efficacy. These patients have been excluded from most randomized clinical trials testing PAH-specific treatments. To date, there is only one study investigating efficacy, safety, tolerability and pharmacokinetics of PAH-specific therapy in patients with PoPAH in a randomized placebo-controlled setting. In this trial the use of the endothelin-1 receptor antagonist macitentan showed clear hemodynamic benefit without safety concerns. However, the drug effects on functional capacity and mortality remain unclear. Here we review the current knowledge on the pathophysiology and management of PoPAH and report a case vignette of a patient with PoPAH due to hepatorenal polycystic disease.

When right ventricular pressure meets volume: The impact of arrival time of reflected waves on right ventricle load in pulmonary arterial hypertension.

Right ventricular (RV) wall tension in pulmonary arterial hypertension (PAH) is determined not only by pressure, but also by RV volume. A larger volume at a given pressure generates more wall tension. Return of reflected waves early after the onset of contraction, when RV volume is larger, may augment RV load. We aimed to elucidate: (1) the distribution of arrival times of peak reflected waves in treatment-naïve PAH patients; (2) the relationship between time of arrival of reflected waves and RV morphology; and (3) the effect of PAH treatment on the arrival time of reflected waves. Wave separation analysis was conducted in 68 treatment-naïve PAH patients. In the treatment-naïve condition, 54% of patients had mid-systolic return of reflected waves (defined as 34-66% of systole). Despite similar pulmonary vascular resistance (PVR), patients with mid-systolic return had more pronounced RV hypertrophy compared to those with late-systolic or diastolic return (RV mass/body surface area; mid-systolic return 54.6 ± 12.6 g m-2 , late-systolic return 44.4 ± 10.1 g m-2 , diastolic return 42.8 ± 13.1 g m-2 ). Out of 68 patients, 43 patients were further examined after initial treatment. At follow-up, the stiffness of the proximal arteries, given as characteristic impedance, decreased from 0.12 to 0.08 mmHg s mL-1 . Wave speed was attenuated from 13.3 to 9.1 m s-1 , and the return of reflected waves was delayed from 64% to 71% of systole. In conclusion, reflected waves arrive at variable times in PAH. Early return of reflected waves was associated with more RV hypertrophy. PAH treatment not only decreased PVR, but also delayed the timing of reflected waves. KEY POINTS: Right ventricular (RV) wall tension in pulmonary arterial hypertension (PAH) is determined not only by pressure, but also by RV volume. Larger volume at a given pressure causes larger RV wall tension. Early return of reflected waves adds RV pressure in early systole, when RV volume is relatively large. Thus, early return of reflected waves may increase RV wall tension. Wave reflection can provide a description of RV load. In PAH, reflected waves arrive back at variable times. In over half of PAH patients, the RV is exposed to mid-systolic return of reflected waves. Mid-systolic return of reflected waves is related to RV hypertrophy. PAH treatment acts favourably on the RV not only by reducing resistance, but also by delaying the return of reflected waves. Arrival timing of reflected waves is an important parameter for understanding the relationship between RV load and its function in PAH.

[Study on the synchronization of biventricular beats with the control mode of left ventricular assist device].

Right ventricular (RV) failure has become a deadly complication of left ventricular assist device (LVAD) implantation, for which desynchrony in bi-ventricular pulse resulting from a LVAD is among the important factor. This paper investigated how different control modes affect the synchronization of pulse between LV (left ventricular) and RV by numerical method. The numerical results showed that the systolic duration between LV and RV did not significantly differ at baseline (LVAD off and cannula clamped) (48.52% vs. 51.77%, respectively). The systolic period was significantly shorter than the RV systolic period in the continuous-flow mode (LV vs. RV: 24.38% vs. 49.16%) and the LV systolic period at baseline. The LV systolic duration was significantly shorter than the RV systolic duration in the pulse mode (LV vs. RV: 28.38% vs. 50.41%), but longer than the LV systolic duration in the continuous-flow mode. There was no significant difference between the LV and RV systolic periods in the counter-pulse mode (LV vs. RV: 43.13% vs. 49.23%). However, the LV systolic periods was shorter than the no-pump mode and much longer than the continuous-flow mode. Compared with continuous-flow and pulse mode, the reduction in rotational speed (RS) brought out by counter-pulse mode significantly corrected the duration of LV systolic phase. The shortened duration of systolic phase in the continuous-flow mode was corrected as re-synchronization in the counter-pulse mode between LV and RV. Hence, we postulated that the beneficial effects on RV function were due to re-synchronizing of RV and LV contraction. In conclusion, decreased RS delivered during the systolic phase using the counter-pulse mode holds promise for the clinical correction of desynchrony in bi-ventricular pulse resulting from a LVAD and confers a benefit on RV function.

Porcine Model of the Arterial Switch Operation: Implications for Unique Strategies in the Management of Hypoplastic Left Ventricles.

There are no reports on the performance of the arterial switch operation (ASO) in a normal heart with normally related great vessels. The objective of this study was to determine whether the ASO could be performed in a healthy animal model. Cardiopulmonary bypass (CPB) and coronary translocation techniques were used to perform ASO in neonatal piglets or a staged ASO with prior main pulmonary artery (PA) banding. Primary ASO was performed in four neonatal piglets. Coronary translocation was effective with angiograms confirming patency. Piglets could not be weaned from CPB due to right ventricle (RV) dysfunction. To improve RV function for the ASO, nine piglets had PA banding. All survived the procedure. Post-banding RV pressure increased from a mean of 20.3 ± 2.2 mmHg to 36.5 ± 7.3 mmHg (p = 0.007). At 58 ± 1 days post-banding, piglets underwent cardiac MRIs revealing RV hypertrophy, and RV pressure overload with mildly reduced RV function. Catheterization confirmed RV systolic pressures of 84.0 ± 6.7 mmHg with LV systolic pressure 83.3 ± 6.7 mmHg (p = 0.43). The remaining five PA banded piglets underwent ASO at 51 ± 0 days post-banding. Three of five were weaned from bypass with patent coronary arteries and adequate RV function. We were able to successfully perform an arterial switch with documented patent coronary arteries on standard anatomy great vessels in a healthy animal model. To our knowledge this is the first time this procedure has been successfully performed. The model may have implications for studying the failing systemic RV, and may support a novel approach for management of borderline, pulsatile left ventricles.

Study on the synchronization of biventricular beats with the control mode of left ventricular assist device / 生物医学工程学杂志

Right ventricular (RV) failure has become a deadly complication of left ventricular assist device (LVAD) implantation, for which desynchrony in bi-ventricular pulse resulting from a LVAD is among the important factor. This paper investigated how different control modes affect the synchronization of pulse between LV (left ventricular) and RV by numerical method. The numerical results showed that the systolic duration between LV and RV did not significantly differ at baseline (LVAD off and cannula clamped) (48.52%

Right ventricle failure in patients treated with left ventricular assist device.

This review article aim to highlight the right ventricular function peri left ventricular assist device implantation, and to assess the incidence, physiopathology, predictors, management and prognosis, of right ventricular failure post-implant.

Transcatheter edge-to-edge tricuspid repair for recurrence of valvular regurgitation after left ventricular assist device and tricuspid ring implantation.

Tricuspid regurgitation in patients with left ventricular assist device (LVAD) has a significant impact on prognosis and quality of life, and its effects on liver and renal function could negatively impact planned heart transplantation. The aim of the present case is to report the feasibility and the clinical impact of tricuspid transcatheter edge-to-edge repair in LVAD patients as adjunctive bridge to transplantation strategy. A 59-year-old female patient previously treated with LVAD implantation (HeartMate III) and tricuspid valve repair with 32 mm rigid ring (Medtronic Contour 3D) as bridge to transplantation developed recurrence of significant tricuspid regurgitation with right ventricular decompensation needing inotropic support. Preoperative echo showed torrential tricuspid valve regurgitation Effective regurgitant orifice area(EROA 1.4 cm2 ) with suspicious of partial detachment of the prosthetic ring. The patient was successfully treated with transcatheter edge-to-edge repair with the MitraClip XTR device. Tricuspid regurgitation was reduced by 50% (postoperative EROA 0.7 cm2 ). She remained stable under continuous inotropic support with no other episodes of right ventricular decompensation and was successfully transplanted 30 days after the clipping procedure. Transcatheter treatment of tricuspid regurgitation in a patient with LVAD was an effective strategy to gain time and bridge the patient to heart transplantation.