High Output State Research Articles

Investigation of metal-insulator-metal waveguides with elliptical-nanodisk resonator for high contrast ratio all-optical logic gates

Abstract This research focuses on the design and analysis of all-optical Exclusive OR(XOR), NOT, and OR logic gates based on metal-insulator-metal waveguides with elliptical-nanodisk resonators. The functionality of the proposed optical logic gates is determined by constructive and deconstructive signals which are applied to the input ports and control ports. To show the logic 0 (low) and logic 1 (high) output states, the limit of threshold transmission is 1.775 × 10−13 ∼0. The transmission (T) and contrast ratio (CR) are obtained to present the performance of the optical logic gates via the method of finite-difference time-domain. The maximum transmission is reached for the OR gate as 1.38 and the highest contrast ratio is 124.75 dB for the XOR and NOT logic gates. The designed logic devices are promising for improving more efficient optical signal information processing devices.

Chaotic responses across the potential barrier of bistable vortex-induced vibration energy harvesters

Large-amplitude interwell limit cycle oscillations (LCOs) are regarded as an ideal high-output state of multistable vibration energy harvesters. However, chaotic responses, which result in lower output voltages than interwell LCOs, can be observed in bistable vortex-induced vibration energy harvesters (VIVEHs). In this paper, the chaos in bistable VIVEHs is investigated through numerical simulation, theoretical analyses, and experimental validation. The distribution of the periodic solutions obtained by the incremental harmonic balance (IHB) method and chaos judgment using Lyapunov exponents are elucidated. It is found that the bistable VIVEH shows intrawell periodic solutions at high reduced wind speeds (RWSs) and period-doubling bifurcation appears with the periodic solutions turning into chaos with decreasing RWS. Analyses of the influence of nonlinear parameters on the chaotic responses identify the nonlinear stiffness as the dominant factor contributing to the chaos. Meanwhile, the chaotic responses and interwell LCOs would exist at the same RWS with different initial states. Finally, wind tunnel experiments confirm the occurrence of homologous chaotic responses of the bistable VIVEH which feature aperiodic jumping back and forth motion between two potential wells, in agreement with numerical simulations. Overall, this paper provides a framework for analyzing the chaotic responses of bistable VIVEHs, offering valuable insights for complex response mechanism understanding.

Beta-blockade for the treatment of refractory hypoxaemia during venovenous extracorporeal membrane oxygenation: An in-silico study.

Venovenous extracorporeal membrane oxygenation (VV ECMO) is used for refractory hypoxemia, although despite this, in high cardiac output states, hypoxaemia may persist. The administration of beta-blockers has been suggested as an approach in this scenario, however the physiological consequences of this intervention are not clear. We performed an in-silico study using a previously described mathematical model to evaluate the effect of beta-blockade on mixed venous and arterial saturations (, SaO2), in three different clinical scenarios and considered the potential effects of beta-blockers on, cardiac output, oxygen consumption and recirculation. Additionally we assessed the interaction of beta-blockade with haemoglobin concentration. In scenario 1: simulating a patient with high cardiac output and partial lung shunt decreased from increased 53.5% to 44.7% despite SaO2 rising from 74.2% to 79.2%. In scenario 2 simulating a patient with high cardiac output and complete lung shunt remained unchanged at 52.2% and SaO2 rose from 71.9% to 85%. In scenario 3 a patient with normal cardiac output and high recirculation fell from 50.8% to 25.5% and also fell from 82.4% to to 78.3%. Across the remaining modelling examples the effect on varied but oxygen delivery was consistently reduced across all scenarios. The administration of beta-blockers for refractory hypoxemia during VV ECMO are unpredictable and may reduce oxygen delivery, although this will vary with patient and circuit features. This study does not support the use of beta-blockers for this indication.

Impact of genotype on multi-organ iron and complications in patients with non-transfusion-dependent β-thalassemia intermedia.

We evaluated the impact of the genotype on clinical and hematochemical features, hepatic and cardiac iron levels, and endocrine, hepatic, and cardiovascular complications in non-transfusion-dependent (NTD) β-thalassemia intermedia (TI) patients. Sixty patients (39.09 ± 11.11years, 29 females) consecutively enrolled in the Myocardial Iron Overload in Thalassemia project underwent Magnetic Resonance Imaging to quantify iron overload, biventricular function parameters, and atrial areas and to detect replacement myocardial fibrosis. Three groups of patients were identified: homozygous β+ (N = 18), heterozygous β0β+ (N = 22), and homozygous β0 (N = 20). The groups were homogeneous for sex, age, splenectomy, hematochemical parameters, chelation therapy, and iron levels. The homozygous β° genotype was associated with significantly higher biventricular end-diastolic and end-systolic volume indexes and bi-atrial area indexes. No difference was detected in biventricular ejection fractions or myocardial fibrosis. Extramedullary hematopoiesis and leg ulcers were significantly more frequent in the homozygous β° group compared to the homozygous β+ group. No association was detected between genotype and liver cirrhosis, hypogonadism, hypothyroidism, osteoporosis, heart failure, arrhythmias, and pulmonary hypertension. Heart remodelling related to a high cardiac output state cardiomyopathy, extramedullary hematopoiesis, and leg ulcers were more pronounced in patients with the homozygous β° genotype compared to the other genotypes analyzed. The knowledge of the genotype can assist in the clinical management of NTD β-TI patients.

Abstract 12993: Higher Risk of Heart Failure in Patients With Sickle Cell Disease

Background: Sickle cell disease (SCD) is a known risk factor for the development of cardiovascular disease. Congestive heart failure (CHF) is a major cardiovascular complication in patients with SCD. A high-output cardiac state and increased systemic vascular resistance in SCD patients lead to ventricular hypertrophy and diastolic dysfunction. The subject of this study is to examine the risk of developing CHF in SCD when compared to patients without SCD using the All of Us Database. Methods: We conducted a propensity score matching (PSM) analysis to evaluate the effect of sickle cell disease (SCD) on the risk of developing congestive heart failure (CHF) in a cohort of 287,012 American individuals enrolled in the All of Us database. Covariates for matching included age, gender, race, ethnicity, income level, education level, marital status, cigarette exposure, alcohol exposure, drug exposure, and comorbidities. The resulting control group (n=761) was matched to the SCD patient group (n=761) based on propensity scores. A logistic regression analysis was then conducted to determine the association between SCD and CHF, adjusting for significant factors. Results: The logistic regression analysis revealed a significant association between SCD and CHF. In the unadjusted model, SCD patients had an odds ratio (OR) of 1.42 (95% CI: 1.09-1.84, p=0.009) for developing CHF compared to the control group. After adjusting for age group, income, marital status, drug exposure, and modified Charlson comorbidity index, the adjusted OR was 1.60 (95% CI: 1.20-2.15, p=0.002). Conclusion: Patients with SCD had an increased risk of developing CHF, compared to propensity score-matched controls.

Prenatal features of aneurysm of the posterior cerebral artery: a case report

BackgroundFetal cerebral aneurysm other than aneurysm of vein of Galen aneurysmal malformation (VGAM) is extremely rare. This report describes prenatal features of aneurysm of the posterior cerebral artery (APCA) with rapid progression and its natural intrauterine course of the disease, which has never been reported.Case presentationThis is the first report of prenatal features of APCA, detected at 34–36 weeks of gestation, simulating choroid plexus cyst or arachnoid cyst. The diagnosis was based on color flow ultrasound with tracing along the course of cerebral arteries. Also, rendered 3D color flow ultrasound was helpful in demonstrating course of the vessels feeding the aneurysm and supporting the diagnosis. The aneurysm showed nature of rapidly progressive changes, leading to leakage resulting in intracerebral and intraventricular hemorrhage as well as high output state associated with anemia. Prenatal diagnosis and management are very challenging. This case ended up with planned delivery at 37 weeks, giving birth to a surviving male newborn, weighing 2600 g. The neonatal CT brain scans and CTA confirmed the prenatal findings. The prognosis was relatively poor because of extensive intracerebral hemorrhage with severe hydrocephalus and brain midline shift. The couple opted for neonatal palliative care without neurosurgical correction.ConclusionThis study demonstrate that the most important tool for prenatal diagnosis is color Doppler ultrasound, which will demonstrate turbulent blood flow. Three-dimension color Doppler ultrasound is helpful in supporting the diagnosis. The case presented here suggests that the disease has a natural course of rapid progression and massive brain destruction or high output congestive heart failure can be expected.

Comparing the hemodynamic effect of a large arteriovenous fistula during high and low cardiac output states.

Background: A large arteriovenous fistula (AVF) is a low-resistant circuit that affects organ perfusion and systemic hemodynamics even in standard conditions. The extent of its' effect in critical states has not been elucidated yet. We used norepinephrine to create systemic vasoconstriction, dobutamine to create high cardiac output, and rapid right ventricle pacing as a model of acute heart failure in a porcine model of high-flow AVF circulation. Methods: The protocol was performed on nine domestic female pigs under general anesthesia. AVF was created by connecting two high-diameter ECMO cannulas inserted in the femoral artery and vein. Continuous hemodynamic monitoring was performed throughout the protocol. Three interventions were performed-moderate dose of norepinephrine (0.25ug/kg/min), moderate dose of dobutamine (10ug/kg/min) and rapid right ventricle pacing to simulate low cardiac output state with mean arterial pressure under 60mmHg. Measurements were taken with opened and closed arteriovenous fistula. Results: Continuous infusion of norepinephrine with opened AVF significantly increased mean arterial pressure (+20%) and total cardiac output (CO) (+36%), but vascular resistance remained virtually unchanged. AVF flow (Qa) rise correlated with mean arterial pressure increase (+20%; R = 0.97, p = 0.0001). Effective cardiac output increased, leading to insignificant improvement in organ perfusion. Dobutamine substantially increased cardiac output with insignificant effect on AVF flow and mean arterial pressure. Carotid artery blood flow increased significantly after dobutamine infusion by approximately 30%, coronary flow velocity increased significantly only in closed AVF state. The effective cardiac output using the heart failure model leading to decrease of carotid artery flow and worsening of brain and peripheral tissue oximetry. AVF blood flow also dropped significantly and proportionally to pressure, but Qa/CO ratio did not change. Therefore, the effective cardiac output decreased. Conclusion: In abovementioned extreme hemodynamic conditions the AVF flow was always directly proportional to systemic perfusion pressure. The ratio of shunt flow to cardiac output depended on systemic vascular resistance. These experiments highlight the detrimental role of a large AVF in these critical conditions' models.

Optimal scheduling of thermal-photovoltaic power generation system considering carbon emission

Increasing the proportion of clean energy is an inevitable trend of high-quality energy development. While enjoying the benefits of clean energy, traditional fossil energy enterprises face great challenges. In this study, coal power and photovoltaic power are selected as examples for analysis. Considering coal consumption, carbon emission, unit ramp conditions and photovoltaic abandonment, a comprehensive income model containing thermal power and photovoltaic power generation is proposed. The objective function of maximizing earnings is established and solved by genetic algorithm. The results show that the overall benefit will increase if the proportion of photovoltaic does not increase blindly. The unreasonable ratio of thermal and photovoltaic power and the imbalance of supply and consumption will lead to the decline of economic benefits and the increase of coal consumption and carbon emission. In the case of a high proportion of clean energy penetration, on the one hand, traditional power plants should be responsible for ensuring the instability of electricity output when the photovoltaic is weak, on the other hand, they need to give up some of the supply proportion when clean power is at a high output state. Therefore, while increasing the proportion of clean energy, it is necessary to improve the speed of load adjustment, the depth of peak regulation and the efficiency of low load work in traditional power plants to ensure the healthy development of new energy.

665 THE UNFORSEEN MECHANISM: A CASE OF DISTRIBUTIVE SHOCK SECONDARY TO REACTIVE HAEMOPHAGOCYTIC SYNDROME LEADING TO SEVERE REVERSIBLE BIVENTRICULAR DYSFUNCTION.

Abstract Distributive shock comprises a variety of processes causing dysregulated vasodilation with consequent life-threatening end-organ dysfunction. While sepsis constitutes by far its most common aetiology, other pathological mechanisms with different therapeutic targets may lead to a similar haemodynamic picture. We hereby present the case of a 35-year-old male with no past cardiological history and a recent diagnosis of stage IVsB Hodgkin's lymphoma relapse 10 years after effective disease eradication with first-line chemotherapy. Shortly after a single cycle of second-line chemotherapy, the patient presented with high fever, acute chest pain and dyspnea associated with marked hypotension and sinus tachycardia. Laboratory tests revealed pancytopenia and raised inflammatory markers as well as evidence of acute kidney injury and hepatocellular damage. Urgent thoracic CT revealed no signs of pneumonia while echocardiography demonstrated severe biventricular dysfunction with 25% left ventricular ejection fraction and severe functional mitral regurgitation. Due to worsening tachypnea and desaturation the patient was intubated and transferred to our Intensive Cardiac Care Unit where urgent instatement of circulatory support with iv fluids, blood transfusions, adrenaline and intra-aortic balloon pump were performed and empirical broad-spectrum antibiotic therapy was started after performing blood cultures from peripheral and central veins. Concurrent right ventricular catheterisation demonstrated high-output cardiac failure (Qs Fick 7.89 Qp/m2, Qs thermodilution 8.0 Qp/m2) with mild increase in biventricular filling pressures and post-capillary pulmonary hypertension. Endomyocardial biopsy in turn revealed only mild subendocardial fibrosis and oedema thus excluding myocarditis as a potential cause for the severe biventricular dysfunction. Due to worsening of renal function with persistent anuria despite circulatory support the patient required continuous veno-venous haemofiltration. Notably, over the coming days no pathogen was isolated from any of the cultures with haemodynamic and respiratory parameters gradually improving, allowing for weaning from circulatory and respiratory support. On further examination of blood tests on admission, hypertriglyceridemia, raised ferritin levels and thrombin consumption were noted. These biochemical features, together with the history of Hodgkin's lymphoma relapse, recent chemotherapy, pancytopenia and splenomegaly, suggestive of natural killer cell dysfunction-related haemophagocytosis, pointed to reactive haemophagocytic syndrome as a potential aetiology of the severe distributive shock (> 99% probability on recently published “HS Score” for Reactive Haemophagocytic Syndrome). This hypothesis was further corroborated by the gradual albeit not complete regression of the severe biventricular dysfunction after haemodynamic support suggesting that this may have represented a byproduct of the patient's high-output state. Unfortunately, due to lymphoma progression with severe multiorgan involvement the patient was admitted shortly after discharge and deceased thereafter. This case provides an example of the diversity of potential disease mechanisms underlying distributive shock where biventricular dysfunction may represent a reversible albeit severe bystander rather than the true driving factor of its life-threatening haemodynamic compromise.

Trading on Sunspots

In a model with multiple Pareto-ranked equilibria, we show that the set of equilibria shrinks if we allow trade in assets that pay based on the realization of a sunspot acting as an equilibrium-selection device. When the probability of a low-output outcome is high, the desire to insure against it leads the poor to promise large transfers to the rich in the high-output state. The rich then lose the incentive to exert the effort needed to sustain the high output. Thus the opening of financial markets may destroy the high equilibrium. (JEL D51, D53, D82, E44, G12, G14, G21)

Functional and Molecular Heterogeneity of Aging Hematopoietic Stem Cells

Background: Aging hematopoiesis is characterized by increased numbers of hematopoietic stem cells (HSCs) that exhibit impaired self-renewal and long-term reconstitution potential. We previously demonstrated that differences in surface expression of c-Kit in young mouse HSCs could identify distinct functional HSC subsets, with c-Kithi HSCs exhibiting reduced self-renewal and megakaryocytic biased differentiation. We therefore sought to determine if similar functional and molecular differences may be observed in old HSCs. Methods: We evaluated c-Kithi and c-Kitlo subsets of HSCs (CD34-CD150+LSK) from young (8-12 wk), and old (18-20 mo) C57BL/6J mice. For competitive transplantation assays, 250 double sorted c-Kithi or c-Kitlo HSCs from aged CD45.2 mice were mixed with 5x105 unfractionated bone marrow mononuclear cells (BMMCs) from young CD45.1 mice. In parallel, we generated the chromatin accessibility and transcriptional profiles of c-Kithi and c-Kitlo HSCs from young and old mice. Results: We first performed competitive transplants of old c-Kithi and c-Kitlo HSCs into young recipients. These studies demonstrated age-related myeloid bias exhibited by both HSC subsets. In addition, similar to young HSCs, old c-Kithi HSCs exhibit significantly reduced long-term reconstitution capacity compared to old c-Kitlo HSCs. Next, to evaluate age-related functional differences, we performed equal competitive transplants in which equal numbers of c-Kithi or c-Kitlo old and young HSCs were transplanted into the same young recipient. These studies demonstrated that c-Kithi HSCs exhibit similar reconstituting capacity independent of age. In contrast, old c-Kitlo HSCs exhibited significantly reduced long-term reconstitution compared to their young counterparts, though with better-preserved self-renewal capacity, as reflected in their self-renewal quotients (SRQ). However, when we quantified the capacity of transplanted HSCs to give rise to downstream committed progenitors and mature hematopoietic cells, calculated as their differentiation quotient (DQ), old c-Kitlo HSCs exhibited markedly reduced DQ compared to their young counterparts. In contrast, c-kithi recipients showed that old c-Kithi HSCs gave rise to mature cell lineages more efficiently. To investigate molecular mechanisms driving heterogeneity in HSC aging, we evaluated the transcriptional profiles of young and old HSCs. Old c-Kitlo HSCs showed significant enrichment of genes associated with inflammation, interferon responses, and the quiescent state in comparison to old c-Kithi HSCs. On the other hand, old c-Kithi HSCs were enriched for cell cycle related and MYC target genes compared to old c-Kitlo HSCs and young HSCs. Old c-Kithi HSCs also exhibited increased expression of genes associated with high cell output state and high mitochondrial membrane potential, which is associated with a more active HSC cell state. To investigate the potential role of chromatin accessibility in determining the observed transcriptional changes, we performed ATAC-seq of young and old HSC subsets. Old HSCs exhibited more open chromatin peaks than young HSCs, with the number of peaks decreasing in the order of old c-Kitlo > old c-Kithi > young c-Kithi > young c-Kitlo HSCs. Evaluation of predicted transcription factor binding sites showed enrichment for CTCF and PU.1 sites in young c-Kitlo and c-Kithi HSCs, respectively, with PU.1 associated with high cell output states. In contrast, old c-Kitlo and c-Kithi HSCs were enriched for ERG and CTCF sites, respectively, with predicted binding sites enriched in genes associated with low and high cell output, respectively. These data suggest that differential ERG binding of quiescence and cellular output-related gene signatures regulate functional differences between old c-Kitlo and old c-Kithi HSCs. Conclusion: Overall, our studies demonstrate functional heterogeneity among old HSCs and identify a novel strategy to identify old HSCs with preserved self-renewal and long-term reconstitution capacity. Identifying and prospectively fractionating old HSCs offers a novel approach for investigating the molecular mechanisms underlying HSC aging.

Abstract 15617: Severe Heart Failure: Fistulous Connection Between Ectatic Left Anterior Descending Artery, Coronary Sinus, and Left Ventricular Cavity

Introduction: Arteriovenous coronary fistula of LAD to the coronary sinus is a rare vascular anomaly present in 0.002% of the general population. We report a rare case of fistulous connection between exceptionally large LAD and coronary sinus into the LV cavity leading to severe systolic heart failure. Case: A 39-year-old male with no past medical history presented to the ED with complaints of dyspnea, chest pain and lower extremity edema for the past 3 months. The chest pain was substernal, squeezing, non-radiating, 2/10 in intensity, exacerbated by exertion and alleviated with rest. The patient did not have any cardiology work up in the past. Vitals were stable. The patient had irregular rhythm with prominent JVD and bilateral lower extremity edema on examination. Troponins were negative, BNP was elevated and thyroid function was normal. Chest x-ray showed cardiomegaly. EKG showed atrial fibrillation with no significant ST segment changes or Q waves. Echocardiogram showed severe systolic left ventricular dysfunction with an ejection fraction of 15-20% and moderate to severe secondary mitral regurgitation. Cardiac catheterization showed large ectatic LAD with mild stenosis in mid segment. An abnormal connection was noted between LAD and coronary sinus draining directly into the left ventricle. He was discharged on guideline directed medical therapy for heart failure. Discussion: Fistula between LAD, coronary sinus and LV cavity is a unique organic heart disease. Our patient presented with heart failure with no apparent identifiable cause. On angiography an ectatic LAD was connected to the coronary sinus and LV cavity which created a high output state on the LV. The management of this rare pathology is complex due to variable presentation and lack of specific treatment guidelines. Careful selection of certain cases for therapeutic intervention can result in better outcomes than medical therapy alone.

Cardiac and Hemodynamic Manifestations of Hereditary Hemorrhagic Telangiectasia.

The autosomal dominant trait hereditary hemorrhagic telangiectasia (HHT) causes multiorgan dysplastic lesions of the vasculature that can activate multiple physiological cascades leading to a broad array of cardiovascular diseases. Up to 78% of patients with HHT develop hepatic arteriovenous malformations (AVMs), which cause a hyperdynamic circulatory state secondary to hepatic/portal shunting. This condition can eventually progress to high-output cardiac failure (HOCF) with continued peripheral tissue hypoxemia. Treatment for HOCF is often limited to supportive measures (diuretics and treatment of anemia); however, recent studies using systemic bevacizumab have shown promise by substantially reducing the cardiac index. In the context of liver AVMs and high cardiac output, the pulmonary vasculature can also experience high flow. Without adequate dilation of pulmonary vessels, post-capillary pulmonary hypertension can develop. Another form of pulmonary hypertension observed in HHT, pulmonary arterial hypertension, is caused by HHT-related mutations in ENG and ACVRL1 causing congestive arteriopathy. Post-capillary pathogenesis is addressed by reducing the high-output state, whereas the pre-capillary state is treated with supportive mechanisms (diuretics, oxygen) and agents targeting pulmonary vasoreactivity: endothelin-1 receptor antagonists and phosphodiesterase-5 inhibitors. If either form of pulmonary hypertension is left untreated or proves refractory and progresses, the common hemodynamic complication is right heart failure. Targeted right heart therapies involve similar strategies to those of pulmonary arterial hypertension, with several experimental approaches under study. In this review, we describe in detail the mechanisms of pathogenesis, diagnosis, and treatment of the hemodynamic complications and associated cardiovascular diseases that may arise in patients with HHT.

Off-label Rescue Agents for Vasoplegic Syndrome after Cardiopulmonary Bypass

Abstract Introduction: Cardiovascular disease is the number one cause of death in the United States today1. Cardiopulmonary bypass (CPB) is a common technique used in the surgical management of cardiovascular disease. A relatively common complication of CPB is vasoplegia, which has an approximate incidence of anywhere from 5-25%1-8. Methylene blue is used to treat vasoplegic syndrome (VS) when higher dose vasopressors are ineffective. Vasoplegic syndrome (VS) is defined as a syndrome of low systemic vascular resistance (SVR) in the presence of normal or high cardiac output1-4. Generally, VS is characterized as a high cardiac output state (CI < 2.2 L/min/m2) with difficulty maintaining a mean arterial pressure (MAP) greater than 60 mmHg despite increasing vasopressor requirements1-3,7. The focus of this case report is to examine methylene blue’s effectiveness in treating vasoplegia after weaning from CPB. This case report will also compare and contrast methylene blue and another rescue agent, hydroxocobalamin, and how they combat vasoplegia. Case presentation: The case involved a 65-year-old male presenting for an aortic root and aortic valve replacement and removal of an abscess in his heart. The patient was under general anesthesia, put on cardiopulmonary bypass and then underwent a deep hypothermic circulatory arrest for the placement of the aortic root graft and aortic valve. Weaning from bypass was difficult as a result of vasoplegia, for which methylene blue was given when vasopressor requirements were increasing. Discussion: Methylene blue is a guanylyl cyclase inhibitor that has been found to increase SVR and decrease vasopressor requirements in vasoplegic syndrome by inhibiting nitric oxide synthase (NOS), thus limiting the production of nitric oxide (NO) as well as inhibiting the enzyme guanylyl cyclase and preventing vasodilation5. The timing of administration of methylene blue is debatable, being that it is commonly given postoperatively, but the literature favors earlier administration in high-risk patients that will be placed on CPB2-5. Typical dosing for methylene blue is 2 mg/kg intravenously (IV) but increasing the dose to 3 mg/kg can be used to account for the larger volume of distribution (Vd) that is present in patients on CPB2. The only true contraindications for methylene blue are a hypersensitivity to the drug and a deficiency in the glucose-6-phosphate dehydrogenase, which is the enzyme that is responsible for turning methylene blue into its metabolites1-8. Treating VS with methylene blue after CPB has shown significantly quicker recovery and normal hemodynamics, shorter duration of vasopressor infusions, less incidence of renal complications, shorter length of stay (LOS) and less 30-day mortality6.

Surgical shunt ligation for a congenital extrahepatic portosystemic shunt with pulmonary hypertension: A case report.

Introduction and importanceCongenital extrahepatic portosystemic shunt (CEPS) presents with various symptoms due to abnormal communication between the portal venous system and inferior vena cava. And Klippel-Trenaunay-Weber syndrome is another rare congenital disorder characterized by vascular malformations.Case presentationA 16-year-old male with Klippel-Trenaunay-Weber syndrome was referred to our hospital for surgical treatment of pulmonary hypertension due to CEPS since childhood. Dyspnea had developed about two years before presentation at our hospital and gradually worsened. Right heart catheterization had revealed pulmonary hypertension and a high cardiac output state associated with a portosystemic shunt. Although pulmonary vasodilators improved the dyspnea, pulmonary hypertension remained. The patient was then referred to our hospital for surgical shunt occlusion. The results of the preoperative and intraoperative shunt occlusion tests were within acceptable limits. Therefore, primary shunt ligation was performed. There were no postoperative complications. Continuous intravenous vasodilator was tapered off four months after discharge. No additional or increased doses of medications were required for four years after surgery.Clinical discussionSurgical shunt ligation for CEPS is effective but can cause acute portal hypertension. Primary shunt ligation could be performed without complications according to the criteria for safe shunt occlusion.ConclusionSurgical portosystemic shunt ligation could be performed safely and ameliorated pulmonary hypertension. Patients with CEPS, especially young patients, should be referred to a tertiary center while asymptomatic, and early therapeutic intervention is necessary.

Predictors Of Right Heart Failure Post Liver Transplant

Background Cardiac complications in liver cirrhosis are associated with increased mortality following liver transplant. Pre-transplant guidelines recommend risk stratification with 2D and dobutamine stress echocardiography, which may lead to coronary angiography or right heart catheterization. There is a paucity of data on the utility of RV hemodynamics during the perioperative period. Our objective was to determine if certain preoperative RV measurements distinguish which patients will experience post liver transplant RV failure. METHODS A retrospective study of liver transplant patients from 2015 through 2020 at the University of Cincinnati Medical Center was performed following IRB approval. Out of 389 patients, 13 had right heart failure based on ICD 10 code and discharge documentation. Preoperative echocardiographic data at baseline and peak stress were collected along with pre and postoperative RHC hemodynamics for comparison to age matched controls. Data was analyzed using two sample T tests in SPSS software. RESULTS Pre-operative RA pressure was higher in the RV failure group (12.5 vs. 6 p<0.001) and baseline PAPI was lower (1.97. vs. 3.54 p=0.02). Baseline TAPSE (2.05 vs. 2.52 p=0.03), stress TAPSE (2.75 vs. 3.22 p=0.02), and TAPSE augmentation (0.13 vs. 0.39 p=0.02) were lower in the RV failure group. Postoperatively, the RV failure group had higher RA pressure (10.01 vs. 7.46 p=0.04) and lower PAPI (1.44 vs. 3.34 p=0.004). There were no differences in mean PA and wedge pressure. The RV failure group had significantly more ventilator days (7.62 vs. 1.92 p<0.001), inotrope use (3.38 vs. 0 p<0.001), and pulmonary vasodilator use (1.93 vs. 0 p<0.001). Thirty day post-transplant mortality was 23% in the RV failure group and 0% in the control group. Data is represented in figure 1. DISCUSSION Cirrhosis causes hyperdynamic cardiac output leading to difficulty determining a pathologic level of dysfunction in these patients. Mean normal TAPSE and PAPI in the literature are 2.0cm and 2.75, respectively, but in our control group mean TAPSE was 2.52cm and PAPI was 3.54. This is likely explained by the high cardiac output state in cirrhosis. In the RV failure group, TAPSE and PAPI were within the normal range suggesting the need to identify a different baseline for patients with a hyperdynamic state due to cirrhosis. Mean PA pressure, commonly used to determine perioperative risk, did not have any discriminating ability between groups. Impaired RV reserve demonstrated by reduced TAPSE augmentation to stress may be a better predictor of RV failure in this patient population and identify patients that may be at risk for significant 30 day post-transplant mortality.

Serial echocardiography assessment and clinical outcomes among pregnant women with Tetralogy of Fallot

Abstract Funding Acknowledgements Type of funding sources: None. Following advancements in intracardiac repair of Tetralogy of Fallot (TOF), a greater proportion of patients survive well beyond child-bearing age. Pulmonary regurgitation (PR) and subsequent progressive right ventricular dilatation occur frequently as an intrinsic complication of surgical repair of TOF. High-output states such as pregnancy may exacerbate these late complications. The advocation of pre-pregnancy pulmonary valve replacement to mitigate pregnancy-related cardiac burden has remained controversial. This study aims to delineate the outcomes of pregnancy among women with repaired TOF. 105 pregnant episodes among were identified from a cohort of 240 adult female patients with TOF between 1990 to 2021. Patients with echocardiographic studies performed within 1 year prior to and following delivery were included for cardiac functional analysis. A paired sample t-test was performed to compare echocardiographic parameters between pre-delivery and post-delivery periods. Linear regression was used to identify changes to identify significant changes in echocardiographic parameters among patients with a baseline of severe PR. Within all pregnant episodes (n = 105), 65 successful pregnancies, 16 spontaneous miscarriages, 21 termination of pregnancies and 3 ectopic pregnancies were recorded. The mean maternal age was 28.9 (±6.7) years with deliveries at 37.86 (30-41) gestational weeks. Cardiovascular events occurred in 19 pregnancies with 4 patients having gestational hypertension, 4 patients with pre-eclampsia toxemia, 7 patients with heart failure symptoms and 4 patients with arrhythmias. Other complications included 4 patients with gestational diabetes mellitus, 3 patients with impaired glucose tolerance, 2 patients with anemia, 3 patients with maternal thyroid disease and 1 patients with proteinuria. Echocardiographic studies demonstrated significant changes in left ventricular ejection fraction (LVEF) (Pre-delivery = 60.69 ±8.73; post-delivery = 59.39 ±9.36) (P = 0.007), left ventricular end diastolic volume (LVEDV) (Pre-delivery: 89.71mL ±18.22mL; Post-delivery: 80.96mL ±12.32mL; P = 0.007), left end systolic volume (LVESV) (Pre-delivery: 35.43 ±12.36; Post-delivery: 32.70 ± 8.83; P = 3.7x10-5) and right ventricular index of myocardial performance score (Pre-delivery: 0.34 ±0.12; Post-delivery: 0.33 ±0.12; P = 0.007). Patients with severe PR was found to have significantly worse right ventricular global longitudinal strain (RV GLS) (P = 0.029). 2 patients progressed to severe PR following delivery. Adult female patients with TOF can have viable pregnancies with acceptable mortality and morbidity. Deterioration in echocardiographic parameters were identified when comparing between pre-delivery and post-delivery studies. TOF patients should be closely monitored throughout and post-delivery for detection of deterioration of cardiac function and clinical symptoms.

Left atrial reservoir strain may be a load independent index of diastolic dysfunction in liver cirrhosis patients

Abstract Funding Acknowledgements Type of funding sources: None. Introduction Cirrhotic cardiomyopathy is characterized by high cardiac output, reduced peripheral resistance and diastolic dysfunction. Specifically, diastolic dysfunction has been correlated with the prognosis in liver cirrhotis patients independently of the disease severity. Left atrial reservoir strain (LASr) is a novel index which is inversely correlated with left ventricular end-diastolic pressure, but has not been adequately studied in cirrhotic patients. Purpose To investigate the correlations between LASr and diastolic function or disease severity in cirrhotic patients. Methods Echocardiographic analysis of 51 consecutive cirrhotic patients was performed and images were analyzed off-line. LASr was calculated semi-automatically using dedicated software and was feasible in 49 patients. Clinical and biochemical examination was used to assess severity of liver disease by calculating MELD-Na score. Results Mean age was 58.0± 8.6 years, 37 (75.5%) were males, mean MELD-Na score was 15.6 ±7.5 and mean LASr was 39.7 ±12.5. LASr correlated with age (r=-0.415, p = 0.003), LAVI (r=-0.329, p = 0.022), e’ (r = 0.476, p = 0.001), E/e (r=-0.401, p = 0.004) and GLS (r=-0.388, p = 0.006), but not with ejection fraction, stroke volume or MELD-Na score. MELD-Na score correlated with ejection fraction (r = 0.316, p = 0.029), stroke volume (r = 0.549, p &amp;lt; 0.001), left atrial volume index (r = 0.575, p &amp;lt; 0.001), GLS (r = 0.521, p &amp;lt; 0.001), right atrial end systolic area (r = 0.368, p = 0.011) and right ventricular diameter (r = 0.541, p &amp;lt; 0.001) reflecting high cardiac output state in patients with advanced cirrhosis. LASr was significantly lower in patients with E/e’ &amp;gt;14 (22.5 ± 13.6) when compared to patients with E/e’ 8-14 (37.3± 10.6, p = 0.039) and E/e’&amp;lt;8 (44.7± 12.0, p = 0.003). The two latter groups also differed significantly (p = 0.034). LASr correlation with E/e’ was the only statistically significant correlation in a multiple regression model including left ventricular end diastolic volume, ejection fraction and left atrial volume (B=-1.371, P = 0.023). Correlation of LASr with MELD-Na score remained non-significant. Conclusion LASr correlates inversely with E/e’ ratio in liver cirrhotic patients, but does not correlate with load dependent echocardiographic parameters and disease severity. Hence in this special population, LASr may be an earlier and more specific index of diastolic dysfunction than traditional echocardiographic indices. Further studies are needed to examine the prognostic significance of LASr in cirrhotic patients.

Role of prenatal cardiovascular magnetic resonance imaging in determining pregnancy risk in repaired Tetralogy of Fallot patients

Abstract Funding Acknowledgements Type of funding sources: None. Addressing pregnancy risks poses as a new challenge among women with repaired tetralogy of Fallot (TOF). The high-output state of pregnancy may predispose women to late complications of repaired TOF. However, guidelines regarding antenatal and or perinatal cardiovascular assessment has not been outlined. Noninvasive modalities such as cardiac magnetic resonance imaging (CMR) that do not require the utilization of ionizing radiation are feasible methods of assessment. Risk stratification of baseline CMR parameters has been sparsely investigated among repaired TOF cohorts. This study aims to identify baseline CMR parameters that may predict adverse outcomes of pregnancy among women with repaired TOF. Sixty-five successful pregnancies were recorded from a cohort of 105 pregnant episodes. Patients with CMR studies performed within 5 years prior to delivery events were included. Adverse clinical outcomes of interest included arrhythmia, heart failure admissions, gestational hypertension, pre-eclampsia toxemia and all-cause mortality. Baseline CMR parameters regarding ventricular mechanics such as left and right ventricular end-diastolic and end-systolic volumes, left and right ventricular ejection fractions and pulmonary regurgitant fraction were measured, and their association with adverse clinical outcomes were evaluated using an independent-samples t-test. Within all 65 successful pregnancies, 26 baseline CMR images were obtained and included in this study. The mean maternal age was 29.7 ± 6.7 years old with a mean birth weight of 2.91 ± 0.49 kg at a mean gestational age of 38.4 ± 2.0 weeks. There was a total of 12 patients with adverse clinical outcome: 5 patients with heart failure hospitalizations, 4 patients with gestational hypertension, 4 patients with arrhythmia and 2 patients with pre-eclampsia toxemia. Assessment of baseline CMR parameters of ventricular mechanics revealed that increased left ventricular end-diastolic volumes (LVEDV) (144.7mL/m2 ± 4.9; P = 0.011), left ventricular end-systolic volumes (LVESV) (65.1mL/m2 ± 9.4; P = 0.004), right ventricular end-diastolic volumes (RVEDV) (235.2 ± 29.0; P = 0.021) and right ventricular end-systolic volumes (RVESV) (122.2mL/m2 ± 38.1; P = 0.033) were associated with an increased incidence of arrhythmia during pregnancy. Nonetheless, there was no significant association between baseline ventricular mechanics with heart failure, gestational hypertension, and pre-eclampsia toxemia. Baseline assessment of cardiac magnetic resonance imaging among pregnant TOF women revealed that larger left and right ventricular volumes were associated with arrythmia development during pregnancy. Further studies with larger cohort sizes evaluating the role of antenatal and perinatal cardiovascular imaging assessment using CMR in predicting the risks of cardiovascular complications during pregnancy are warranted.

High Output Heart Failure in Multiple Myeloma: Pathogenetic Considerations

Simple SummaryMultiple myeloma is a plasma cell disorder that accounts for around 10% of all haematological malignancies. This neoplasia is often associated with a significant prevalence of cardiovascular complications resulting from several factors, unrelated and/or related to the disease. Among cardiovascular complications, the high output heart failure is of great importance as it is related to a worse prognosis for patients. It is important to point out that, despite the availability of more and more numerous and effective drugs, myeloma remains an incurable disease, with frequent relapses and several treatment lines, with the need, therefore, for a careful evaluation of patients, especially from a cardiological point of view. For this reason, we are proposing a comprehensive overview of different pathogenetic mechanisms responsible for high output heart failure in multiple myeloma, including artero-venous shunts, enhanced angiogenesis, glutamminolysis, hyperammonemia and hemorheological alterations, with the belief that a multidisciplinary approach, in clinical evaluation is critical for the optimal management of the patient.The high output heart failure is a clinical condition in which the systemic congestion is associated to a high output state, and it can be observed in a non-negligible percentage of hematological diseases, particularly in multiple myeloma, a condition in which the risk of adverse cardiovascular events may increase, with a worse prognosis for patients. For this reason, though an accurate literature search, we provided in this review a complete overview of different pathogenetic mechanisms responsible for high output heart failure in multiple myeloma. Indeed, this clinical finding is present in the 8% of multiple myeloma patients, and it may be caused by artero-venous shunts, enhanced angiogenesis, glutamminolysis, hyperammonemia and hemorheological alterations with increase in plasma viscosity. The high output heart failure in multiple myeloma is associated with significant morbidity and mortality, emphasizing the need for a multidisciplinary approach.