High Output State Research Articles

Pathophysiology of High Output Arteriovenous Fistula with Heart Failure: A Systematic Review and Meta-analysis

Introduction: Arteriovenous Fistula (AVF) is extensively used as vascular access for haemodialysis patients. It induces a high output state, which is associated with cardiac remodeling. With High Output Heart Failure (HOHF), the AVF occupies a low pressure; reduced vascular resistance and increased venous return. The High Output Arteriovenous Fistula with Heart Failure (HOHF-AVF) patients often undergo a comprehensive assessment of type of underlying diseases, the degree of vasodilatation along with laboratory investigations and cardiac imaging. Hence identification of the pathophysiological determinants of HOHF-AVF is intriguing. Aim: To identify the pathophysiological determinants of HOHF-AVF. Materials and Methods: This systematic review was conducted from May 2021 to December 2021 at the Department of Cardiovascular Surgery, Imperial College, United Kingdom. Randomised Controlled Trials (RCTs), cohort, case-control, cross-sectional and descriptive studies, conducted on adult patients who underwent AVF creation or ligation and addressed the pathophysiological determinants of HOHFAVF were included. Studies conducted among Paediatric cases, case reports, and case series were excluded. Medline (PubMed), EMBASE, ProQuest, and the Cochrane database were searched, by utilising the key words {[(“HOHF” OR “High output heart failure”) AND (“AVF” OR “Arteriovenous fistula”)] AND (“LV parameters” OR “Structural Characteristics” OR “Echocardiographic indices)}. The searches were restricted from January 2000 to October 2021 with studies published in the English language. All the included studies were subjected to critical appraisal using the “Cochrane risk of bias assessment tool” for RCTs, and the “Joanna Briggs Institute (JBI) checklist” for cohort, case-control, cross-sectional and descriptive studies. For meta-analysis Mantel-Haenszel Odds Ratio (M.H. O.R.) with its 95% Confidence Interval (C.I), Mean Difference (M.D) with its 95 % C.I were computed. The Review Manager Software (Rev Man 5, Cochrane collabouration, Oxford, England) was used for data analytics. Results: Overall, 115 citations were identified from the initial search, of which 29 studies were retrieved. Later, 14 studies were excluded. Of the remaining 15 studies, 12 were subjected to meta-analysis. There was a change in Left Ventricular (LV) end diastolic diameter (M.D=2.0; p<0.001; 95% C.I=1.13 to 2.86), and cardiac index (M.D=0.63; p<0.001, 95% C.I=0.46 to 0.79) from baseline to atleast three months of postsurgery among HOHF-AVF patients. According to the AVF flow, there was a change in LV systolic diameter (M.D=-18.90; p<0.01; 95% C.I=-22.84 to-14.96), cardiac index (M.D=0.50; p=0.007; 95% C.I=0.14 to 0.86) and tricuspid annular plane systolic excursion (M.D=3.90; p=0.03; 95% C.I=0.30 to 7.50). Conclusion: Left ventricular end diastolic diameter and cardiac index were found to be the major determinants for a HOHFAVF. The left ventricular mass index, ejection fraction, posterior wall thickness, interventricular septum were not associated with HOHF-AVF. Left ventricular systolic diameter, cardiac index and tricuspid annular plane systolic excursion were the determinants of AVF flow.

Prevalence of Venovenous Shunting and High-Output State Quantified with 4D Flow MRI in Patients with Fontan Circulation.

To assess the ability of four-dimensional (4D) flow MRI to quantify flow volume of the Fontan circuit, including the frequency and hemodynamic contribution of systemic-to-pulmonary venovenous collateral vessels. In this retrospective study, patients with Fontan circulation were included from three institutions (2017-2021). Flow measurements were performed at several locations along the circuit by two readers, and collateral shunt volumes were quantified. The frequency of venovenous collaterals and structural defects were tabulated from concurrent MR angiography, contemporaneous CT, or catheter angiography and related to Fontan clinical status. Statistical analysis included Pearson and Spearman correlation and Bland-Altman analysis. Seventy-five patients (mean age, 20 years; range, 5-58 years; 46 female and 29 male patients) were included. Interobserver agreement was high for aortic output, pulmonary arteries, pulmonary veins, superior vena cava (Glenn shunt), and inferior vena cava (Fontan conduit) (range, ρ = 0.913-0.975). Calculated shunt volume also showed strong agreement, on the basis of the difference between aortic and pulmonary flow (ρ = 0.935). A total of 37 of 75 (49%) of the patients exhibited shunts exceeding 1.00 L/min, 81% (30 of 37) of whom had pulmonary venous or atrial flow volume step-ups and corresponding venovenous collaterals. A total of 12% of patients (nine of 75) exhibited a high-output state (>4 L/min/m2), most of whom had venovenous shunts exceeding 30% of cardiac output. Fontan flow and venovenous shunting can be reliably quantified at 4D flow MRI; high-output states were found in a higher proportion of patients than expected, among whom venovenous collaterals were common and constituted a substantial proportion of cardiac output.Keywords: Pediatrics, MR Angiography, Cardiac, Technology Assessment, Hemodynamics/Flow Dynamics, Congenital Supplemental material is available for this article. © RSNA, 2021.

52-Year-Old Woman With Palpitations, Abdominal Distension, and Severe Abdominal Pain

52-Year-Old Woman With Palpitations, Abdominal Distension, and Severe Abdominal Pain

A case report: percutaneous management of high-output heart failure from iatrogenic aortocoronary venous grafting to the coronary sinus

BackgroundAortocoronary arteriovenous fistula (ACAVF) due to iatrogenic bypass grafting to a cardiac vein is an exceedingly rare complication resulting from coronary artery bypass grafting (CABG) surgery. If not identified in a timely fashion, ACAVF has known significant clinical consequences related to left to right shunting and possible residual myocardial ischemia.Case presentationAn 82-year-old male with a history of CABG, presented with dyspnea. Over the span of 2 years following CABG, the patient experienced progressive exertional dyspnea and peripheral edema. The patient was found to have a new cardiomyopathy with a severely reduced ejection fraction at 30–35%. The patient underwent diagnostic left heart catheterization, and an ACAVF was discovered between a saphenous vein graft and the coronary sinus. The patient underwent successful percutaneous coiling of the ACAVF with no residual flow. Follow-up echocardiography at 3 months revealed restoration of left ventricular systolic function to 50% and significant improvement in heart failure symptoms.ConclusionsACAVF is an exceedingly rare iatrogenic complication of CABG that may result in residual ischemia from the non-grafted myocardial territory and other sequelae relating to left to right shunting and a high-output state. Management for this pathology includes but is not limited to the use of percutaneous coiling, implantation of covered stents, graft removal and regrafting, and ligation.

Cardiac failure and pulmonary hypertension secondary to renal arteriovenous malformation: a case report

BackgroundHeart failure is usually associated with a low-cardiac-output state; however, a minority of these patients are characterized by a high-output cardiac state, described as a cardiac index of > 4 L/minute/m2. Usually such circulation is associated with low systemic vascular resistance or arteriovenous malformation (AVM), resulting in depressurized circulation and a high-output cardiac state. Treating physicians should be cognizant of such pathology when investigating patients with heart failure. As an example, renal arteriovenous malformations are a rare vascular phenomena that are typically the result of iatrogenic, traumatic or congenital etiology. Generally, non-salient, most are detected as an incidental finding.Case presentationA 75-year-old Afro-Caribbean man with multiple comorbidities presented to the emergency department with a 6-month history of heart failure symptoms. Cardiac catheterization demonstrated a giant right renal AVM leading to a significant left-to-right, post-tricuspid shunt that was treated with transcatheter coiling.ConclusionsWe present this case to emphasize the significance of a detailed workup in a patient with heart failure symptoms.

Hybrid and parallel extracorporeal membrane oxygenation circuits

Hybrid and parallel extracorporeal membrane oxygenation circuits

Arteriovenous fistula-induced cardiac remodeling shows cardioprotective features in mice

ObjectiveArteriovenous fistulae (AVF) placed for hemodialysis have high flow rates that can stimulate left ventricular (LV) hypertrophy. LV hypertrophy generally portends poor cardiac outcomes, yet clinical studies point to superior cardiac-specific outcomes for patients with AVF when compared with other dialysis modalities. We hypothesize that AVF induce physiologic cardiac hypertrophy with cardioprotective features. MethodsWe treated 9- to 11-week-old C57Bl/6 male and female mice with sham laparotomy or an aortocaval fistula via a 25G needle. Cardiac chamber size and function were assessed with serial echocardiography, and cardiac computed tomography angiography. Hearts were harvested at 5 weeks postoperatively, and the collagen content was assessed with Masson's trichrome. Bulk messenger RNA sequencing was performed from LV of sham and AVF mice at 10 days. Differentially expressed genes were analyzed using Ingenuity Pathway Analysis (Qiagen) to identify affected pathways and predict downstream biological effects. ResultsMice with AVF had similar body weight and wet lung mass, but increased cardiac mass compared with sham-operated mice. AVF increased cardiac output while preserving LV systolic and diastolic function, as well as indices of right heart function; all four cardiac chambers were enlarged, with a slight decrement in the relative LV wall thickness. Histology showed preserved collagen density within each of the four chambers without areas of fibrosis. RNA sequencing captured 19 384 genes, of which 857 were significantly differentially expressed, including transcripts from extracellular matrix-related genes, ion channels, metabolism, and cardiac fetal genes. The top upstream regulatory molecules predicted include activation of angiogenic (Vegf, Akt1), procardiomyocyte survival (Hgf, Foxm1, Erbb2, Lin9, Areg), and inflammation-related (CSF2, Tgfb1, TNF, Ifng, Ccr2, IL6) genes, as well as the inactivation of cardiomyocyte antiproliferative factors (Cdkn1a, FoxO3, α-catenin). The predicted downstream effects include a decrease in heart damage, and increased arrhythmia, angiogenesis, and cardiogenesis. There were no significant sex-dependent differences in the AVF-stimulated cardiac adaptation. ConclusionsAVF stimulate adaptive cardiac hypertrophy in wild-type mice without heart failure or pathologic fibrosis. Transcriptional correlates suggest AVF-induced cardiac remodeling has some cardioprotective, although also arrhythmogenic features. (JVS–Vascular Science 2021;2:110-28.) Clinical RelevanceArteriovenous fistulae (AVF) are commonly used as access for hemodialysis in patients with end-stage renal disease. AVF induce a high-output state that is associated with long-term structural cardiac remodeling, including left ventricle hypertrophy, but this element has uncertain clinical significance. Although left ventricle hypertrophy has traditionally been associated with an increased risk of cardiovascular disease, clinical studies have suggested that cardiac-specific outcomes of patients with end-stage renal disease were better with AVF compared with other dialysis modalities. This study uses a mouse model of AVF to study the structural, functional, and molecular correlates of AVF-induced cardiac remodeling. It finds that AVF causes an adaptive cardiac hypertrophy without functional decline or fibrosis. Transcriptional correlates suggest an electrical remodeling and the upregulation of proangiogenic, procardiogenic, and prosurvival factors, implying that AVF-induced cardiac hypertrophy is potentially cardioprotective, but also arrhythmogenic.

Underlying Causes of High Output Heart Failure

In the U.S., each year, there are more than 500,000 new cases of all types of heart failure. With high output cardiac failure, there is an elevated cardiac output associated with several conditions and diseases, including obesity, chronic anemia, systemic arterio-venous fistula, hypercapnia, mitochondrial dysfunction, and hyperthyroidism. The underlying pathophysiologic mechanisms relate to a reduction in systemic vascular resistance from arterio-venous shunting or peripheral vasodilation. Often there is a decrease in systemic arterial blood pressure and neurohormonal activation leading to heart failure symptoms of dyspnea and fatigue. In a persistent high output state, patients may experience tachycardia, valvular abnormalities, and ventricular dilatation and/or hypertrophy. In this article, there is a review of high output heart failure, including the prevalence, pathophysiology, and common clinical causes of this disease.

Normative Reference Values of Cardiac Output by Pulsed-Wave Doppler Echocardiography in Adults

Cardiac output (CO) is routinely assessed by pulsed-wave Doppler echocardiography, yet reference values in adults are lacking. We aim to establish normative values of CO and cardiac index (CI) by pulsed-wave Doppler-echocardiography and to analyze their relation with gender and age in nonobese and obese adults. We included 4,040 adults (mean age: 55 years, 53% women, 950 obese [body mass index ≥30 kg/m²]) with normal blood pressure, no history of cardiovascular disease, and normal transthoracic echocardiography. Normative reference CO and CI values for were calculated in 3,090 nonobese patients by quantile regression. CO normal limits were lower in females than in males (lower limit: 3.3 vs 3.5 L/min, upper limit: 7.3 vs 8.2 L/min). CI normal limits were identical for both genders (lower limit: 1.9 L/min/m², upper limit: 4.3 L/min/m²). Although the relation of CO to age was weak and observed only in women, CI of both genders was not influenced by age. CO of obese patients was significantly greater than that of their nonobese counterparts. CI of obese patients was not influenced by age and gender and was not significantly different than that of nonobese patients (lower limit 1.8 L/min/m², upper limit 4.1 L/min/m² for both genders). In conclusion, in a large adult population we establish normative reference values for CO and CI measured by Doppler-echocardiography. CI is a remarkably stable parameter that is not influenced by age, gender, and body size and should be used to define low- and high-output states.

Cardiomyopathy in Sickle Cell Disease.

Sickle cell disease (SCD) is an inherited disorder that occurs due to point mutation in the beta-globin chain resulting in the production of hemoglobin S that tends to become rigid and sickle-shaped under low oxygen concentration. These sickle-shaped red blood cells (RBCs) obstruct the blood vessels leading to reduced blood flow to the organs, causing ischemia and tissue fibrosis. These sickle RBCs being abnormal in shape are frequently sequestered by the spleen, creating a state of chronic anemia in the body. This chronic anemia leads to a high cardiac output state causing cardiac remodeling. To tackle chronic anemia, patients are frequently treated with blood transfusions that makes them more prone to the risk of iron overload (from newly transfused RBCs and iron release from the RBCs that just got sequestered as well as from volume overload) and volume overload causing left ventricular (LV) dilation. The above-mentioned mechanism of cardiac hypertrophy, along with LV dilation together, makes SCD-related cardiomyopathy unique cardiomyopathy with features of restrictive cardiomyopathy with LV dilation. It is interesting to note here that even though there is a presence of LV dilatation, Systolic dysfunction is very uncommon in SCD-related cardiomyopathy.

P1719 A rare complication of homozygous sickle cell disease and high output cardiac failure

Abstract Introduction/Background Sickle cell disease (SCD) is an autosomal recessive blood disorder characterised by chronic anaemia and abnormally shaped red blood cells. SCD impacts multiple organ systems causing effects on morbidity and mortality, including cardiovascular (CV). Long term SCD can have a significant impact on the heart through multiple pathways, including chronic anaemia, microvascular dysfunction and the development of hypertension and chronic kidney disease, leading to the development of a high-output state and adverse cardiac remodelling. We report a rare case of homozygous SCD with the development of high output cardiac failure complicated by the development of associated pulmonary hypertension. Case summary A 58 yr old female patient (Height 158cm, weight 51.25kg, cardiac index 4.01 L/min/m²) with known homozygous SCD (HbSS) undergoing regular transfusions for chronic anaemia was admitted following a routine transthoracic echocardiogram (Figure 1a & 1b) due to the presence of a moderate sized global pericardial effusion, severe tricuspid regurgitation, dilated right heart with impaired longitudinal function, and good left ventricular (LV) systolic function (LVEF Simpson’s biplane = 62 +/- 5%). In the months preceding this, the patient described progressive dyspnoea associated with decreasing workload and orthopnoea. On clinical examination there was evidence of right sided heart failure. Blood results demonstrated a longstanding anaemia (Hb 57 g/L) with MCV 109.6. NT-proBNP was 10233 ng/L. Cardiac magnetic resonance imaging demonstrated LV dilatation with hyperdynamic function, severe LV hypertrophy, and impaired longitudinal function (global longitudinal strain -9.7%). Cardiac output was elevated at 6.5 L/min. There was no late gadolinium enhancement and T2* mapping did not demonstrate cardiac iron loading (29.6ms). Right heart catheterisation confirmed pulmonary hypertension (pulmonary artery pressure 55/33, mean 46mmHg) due to left heart disease (PC wedge pressure (24/30, mean 24mmHg). The pericardial effusion was drained and the aspirate demonstrated a cellular infiltrate reflecting pericardial inflammation (moderate pus cells, no growth after 48hrs, total protein = 56 g/L, no histological evidence of malignancy). Additionally, the patient underwent intravenous diuresis and blood transfusion with improvement in clinical status. Discussion We report a rare cause of pulmonary hypertension due to elevated left ventricular end-diastolic pressure as a result of long-term high cardiac output in a patient who has established homozygous SCD. Long-term adverse cardiac remodelling in SCD is well described. Pulmonary hypertension is a rare multifactorial complication of this process and the precise mechanisms remain unclear. It confers a poor prognosis and the only current treatment is the management of the underlying condition. Pulmonary hypertension should always be considered in SCD patients with clinical and cardiac imaging evidence. Abstract P1719 Figure 1

P5263Genotype and cardiac findings in non transfusion dependent thalassemia patients

Abstract Background In non transfusion dependent thalassemia (NTDT) the lack of a clear genotype-phenotype relationship complicates the already complex and extensive scenario in clinical practice. Purpose Our aim was to detect if the presence of a β°/β° homozygous genotype was associated to different rate of cardiac findings by Cardiovascular Magnetic Resonance (CMR) and cardiac complications. Methods We considered 81 patients with thalassemia intermedia never transfused o who received occasional transfusions (37.7±11.4 years, 39 females) consecutively enrolled in the Myocardial Iron Overload in Thalassemia project. CMR was used to quantify iron overload (T2* technique), biventricular morphological and functional parameters (cine sequences), and the presence of myocardial fibrosis (late gadolinium enhancement-LGE technique). All cardiac complications were classified according to international guidelines. Results Two groups of patients were identified: non homozygous β°/β° genotype (N=61) and homozygous β°/β° genotype (N=20.) No significant differences for sex and age were found between the groups. Patients with homozygous β°/β° genotype had lower mean haemoglobin levels (8.6±1.1g/dl vs 9.2±1.2 g/dl) but the difference did not reach the statistical significance (P=0.060). No patient showed cardiac iron and global heart T2* values were comparable between the two groups. Left atrial area index, left ventricular (LV) end-diastolic, end-systolic and stroke volume indexes, LV mass index, right ventricular end-diastolic and end-systolic volume indexes were significantly higher in the homozygous β°/β° group (see Table). Frequencies of heart failure and arrhythmias were comparable between the groups. Non-β0/β0 homozygous genotype β0/β0 homozygous genotype P Left Atrial Area (cm2/m2) 13.87±2.59 16.63±2.59 0.001 LV EDVI (ml/m2) 94.88±15.59 112.94±21.52 0.003 LV ESVI (ml/m2) 35.22±9.55 41.88±9.70 0.018 LV SVI (ml/m2) 61.98±12.57 69.81±11.20 0.029 LV mass index (g/m2) 61.26±10.15 68.63±15.89 0.030 RV EDVI (ml/m2) 91.27±23.50 107.53±23.87 0.019 RV ESVI (ml/m2) 33.93±17.55 40.81±15.20 0.043 Conclusions Heart remodelling related to a high cardiac output state cardiomyopathy was more pronounced in patients with homozygous β°/β° genotype. These data can support the knowledge of different phenotypic groups in the management of NTDT patients.

Preoperative Noncoronary Cardiovascular Assessment and Management of Kidney Transplant Candidates.

The pretransplant risk assessment for patients with ESKD who are undergoing evaluation for kidney transplant is complex and multifaceted. When considering cardiovascular disease in particular, many factors should be considered. Given the increasing incidence of kidney transplantation and the growing body of evidence addressing ESKD-specific cardiovascular risk profiles, there is an important need for a consolidated, evidence-based model that considers the unique cardiovascular challenges that these patients face. Cardiovascular physiology is altered in these patients by abrupt shifts in volume status, altered calcium-phosphate metabolism, high-output states (in the setting of arteriovenous fistulization), and adverse geometric and electrical remodeling, to name a few. Here, we present a contemporary review by addressing cardiomyopathy/heart failure, pulmonary hypertension, valvular dysfunction, and arrhythmia/sudden cardiac death within the ESKD population.

Confidence Collapse in a Multi-Household, Self-Reflexive DSGE Model

We investigate a multi-household DSGE model in which past aggregate consumption impacts the confidence, and therefore consumption propensity, of individual households. We find that such a minimal setup is extremely rich, and leads to a variety of realistic output dynamics: high output with no crises; high output with increased volatility and deep, short lived recessions; alternation of high and low output states where relatively mild drop in economic conditions can lead to a temporary confidence collapse and steep decline in economic activity. The crisis probability depends exponentially on the parameters of the model, which means that markets cannot efficiently price the associated risk premium. We conclude by stressing that within our framework, narratives become an important monetary policy tool, that can help steering the economy back on track.

PH Grand Rounds: A Case of Pulmonary Hypertension Associated With High Cardiac Output State from Arteriovenous Fistula–Or Is It?

PH Grand Rounds: A Case of Pulmonary Hypertension Associated With High Cardiac Output State from Arteriovenous Fistula–Or Is It?

SAT-593 Thyrotoxic Heart Disease: Rare but Serious Manifestation of Congestive Heart Failure

Background: Excess thyroid hormone alters the hemodynamics of the heart and vascular system resulting in a hyper-dynamic circulatory state which can lead to thyrotoxic heart disease. Clinical case: A 48-year-old male presented to the hospital with several days of rapid heart rate and weakness. He denied prior medical history, medication or supplement intake. Pertinent exam revealed a very thin, hoarse gentleman with shallow breathing and obvious hand tremors; heart exam with irregular rate and tachycardia, absent peripheral edema and bibasilar crackles bilaterally. EKG was consistent with atrial fibrillation with rapid ventricular response. Lab work revealed a pro-BNP of 4000 and positive D-dimer. CTA-Thorax was consistent with CHF with cardiomegaly, large pleural effusions, pulmonary edema and an incidental finding of thyromegaly. Echocardiogram revealed global LV hypokinesis with Ejection Fraction of 10-15%. TSH was <0.005, free Thyroxine >8.00, and Triiodothyronine was 27.04. Thyroid ultrasound showed heterogeneous enlarged gland with hypervascularity and no focal nodules. Graves’ Disease was confirmed with thyroid stimulating Immunoglobulin of 507. Methimazole and hydrocortisone were initiated along with Metoprolol and digoxin for rate control. Thyroid hormone has significant impact on cardiac function, structure and the vascular system. In the vasculature, T3 works to decrease systemic vascular resistance via direct vasodilatation. The decrease in SVR activates RAAS resulting in retention of sodium and fluid. Thyroid hormone also stimulates erythropoiesis which results in an increase in blood volume and stroke volume. In the heart, T3 enters the myocyte via specific transport proteins and via transcription-and non-transcription-mediated effects, increases contractility and relaxation of the cells. Given the increased metabolism, low SVR and increase in total blood volume, this creates a high cardiac output state. Untreated high-output state leads to ventricular dilatation, persistent tachycardia and eventual heart failure. Thus, prompt diagnosis and treatment of cardiac dysfunction is key. Of most importance is correction of thyroid dysfunction with either anti-thyroid medication, radioactive iodine ablation or thyroidectomy. This can possibly reverse and “cure” patient’s systolic heart failure. Conclusion: We present a case of thyrotoxicosis -induced cardiomyopathy with left ventricular ejection fraction of 10% secondary to undiagnosed Graves disease and emphasize the importance of thyroid disease as a possible cause of systolic heart failure.

Credit Allocation, Pollution, and Sustainable Growth: Theory and Evidence from China

ABSTRACT This article studies how credit decisions made by banks affect environmental pollution and the sustainable growth path. Our model suggests that with credit discrimination, the economy may experience a high output and heavy pollution steady state, but there will be welfare losses. Based on the model, we perform an empirical study using panel data from 30 provinces in China. The study results show that credit preference toward highly polluting sectors has an adverse impact on the environment. Arguably, encouraging sustainable banking may help developing countries like China to address environmental challenges.

Pulmonary hypertension and severe right heart failure following lumbar spinal surgery

Pulmonary hypertension is a disease process affecting the pulmonary circulation and is defined by an increase in pulmonary artery pressure subsequently causing right ventricular failure. Vascular complications, including arteriovenous fistulae, are recognised, but are uncommon complications of spinal surgery. Arteriovenous fistulae increase venous return to the right heart and can induce a high-output cardiac state, mimicking pulmonary arterial hypertension and right heart failure. We present a 47-year-old man with a 1 year history of worsening dyspnoea, exertional pre-syncope and leg swelling presenting with severe right heart failure. The previous year, he had complex spinal surgery, which included discectomy, laminectomy and bilateral nerve reconstruction at L5-S1 level. Initial non-invasive investigations including echocardiography and chest imaging raised the possibility of right heart failure presumed secondary to pulmonary vascular disease. Clinical examination and right heart catheterisation were in keeping with a high cardiac output state, and invasive saturation monitoring was suggestive of a sub-diaphragmatic shunt. Subsequent imaging confirmed the presence of an iatrogenic ilio-iliac arteriovenous fistula. The patient underwent urgent endovascular repair, which resulted in resolution of his symptoms and haemodynamics. We describe the case and present a review of the relevant literature.

The High Output State of Sickle Cell Patients: Associations with Anemia-Related Organ Damage

Introduction:As longevity of sickle cell disease (SCD) patients increases, chronic organ damage becomes more prevalent. Tricuspid regurgitation velocity (TRV) ≥2.5 m/sec) has long been considered a reliable indicator of pulmonary hypertension (PH). However, studies using right heart catherization confirmed PH in only 25% of patients with TRV elevation, despite the independent association of an elevated TRV with mortality. Since TRV elevation is also associated with anemia and cardiac remodeling on trans-thoracic echocardiography (TTE), we hypothesized that an elevated TRV may also identify SCD patients with a hyperdynamic circulation due to severe anemia, putting them at higher risk for anemia-related organ damage and early mortality.We aimed to determine the associations between TRV elevation and other high output parameters on TTE with anemia-related organ damage and to assess what echocardiographic parameters predict anemia-related organ damage and mortality.Methods:In this retrospective, longitudinal study, SCD patients were followed from the oldest TTE onwards. At baseline and after follow-up, TTE parameters of cardiac function (including TRV and signs of volume and pressure overload), anemia-related organ damage (microalbuminuria, renal failure, stroke, leg ulcers, priapism, diastolic dysfunction) and mortality were assessed. Logistic and cox regression analyses were applied to analyze associations between baseline echocardiographic findings and laboratory results with development of anemia-related organ damage during follow-up to identify predictors of organ damage.Results:In total 254 patients were included in the study cohort. The mean follow-up was 6.0 years (4.0-8.0 yr). Elevated TRV was found at baseline in 58/254 (22.8%) patients versus 196/254 (77.2%) patients with a normal TRV. Patients with an elevated TRV had an increased cardiac output (59 dL/min vs. 52 dL/min; P <0.01), E-wave velocity (104 cm/sec vs. 94 cm/sec; P=.03), septal E/e‘-ratio (9.2 vs. 7.9; P=.02), left ventricular (LV) mass index (111 g/m2 vs. 94 g/m2; P <0.01) and left atrial (LA) volume index (50 g/m2 vs. 39 g/m2; P <0.01) compared to patients with a normal TRV, which remained unchanged during follow-up. At baseline and upon follow up microalbuminuria (28% vs. 15%; P 0.03) and renal failure (7% vs. 0%; P <0.01) were more prevalent in patients with TRV elevation as compared to patients without TRV elevation. The composite incidence of new forms of anemia-related organ damage after follow-up was higher in patients with an elevated TRV (45% vs. 27%; P 0.02). An elevated LV mass index (representing pressure overload) and septal E/e‘-ratio (representing volume overload) were associated with TRV and a higher prevalence of anemia-related organ damage at baseline, but not with new organ damage upon follow-up or mortality. Predictors of organ damage after follow-up were hemoglobin level (OR 0.7 [0.5 - 0.9]; P <0.01) and age (OR 3.1 [1.7 - 5.5]; P <0.01) and new organ damage was predicted by lactate dehydrogenase (LDH) (OR 1.5 [1.1-2.0]; P=.02) and age (OR 2.0 [1.3 - 3.0]; P <0.01).Conclusion:A high output state in SCD patients is associated with an elevated TRV and anemia-related organ damage, in particular nephropathy, mainly as a consequence of severe anemia and increasing age. These associations may better explain early mortality in these patients despite the fact that only a limited part of these patients do have pulmonary hypertension. Patients with an elevated TRV or other signs of a high output state are at risk of anemia-related organ damage (in particular nephropathy) and should be monitored closely. Early administration of available treatment modalities should be considered. DisclosuresNo relevant conflicts of interest to declare.

B0 Vs. Non-B0 Genotype: Differences in Non-Transfusion-Dependent Thalassemia Patients

Background: In non transfusion dependent thalassemia (NTDT) the lack of a clear genotype-phenotype relationship complicates the already complex and extensive scenario in clinical practice. Our aim was to detect if the presence of a β°/β° homozygous genotype is associated to increased iron overload and rate of complications.Methods: We considered 81 patients with thalassemia intermedia never transfused o who received occasional transfusions (37.7±11.4 years, 39 females) enrolled in the Myocardial Iron Overload in Thalassemia (MIOT) project. Magnetic Resonance Imaging (MRI) was used to quantify iron overload (T2* technique), biventricular morphological and functional parameters (cine sequences), and the presence of myocardial fibrosis (late gadolinium enhancement-LGE technique). All complications were classified according to international guidelines.Results: Two groups of patients were identified: non homozygous β°/ β° genotype (N=61) and homozygous β°/ β° genotype (N=20.) No significant differences for sex and age were found between the groups.The frequency of non chelated patients was significantly lower in the homozygous β°/β° group (17.6% vs 49.1%; P=0.026) and the frequency of desferrioxamine therapy was 70.6 in the homozygous β°/β° group and 43.4 in the non homozygous β°/β° group (P=0.051).Patients with homozygous β°/β° genotype had lower mean haemoglobin levels (8.6±1.1g/dl vs 9.2±1.2 g/dl) but the difference did not reach the statistical significance (P=0.060).Serum ferritin levels, liver transaminases and MRI liver iron concentarion (LIC) values were comparable between the groups.No patient showed cardiac iron and global heart T2* values were comparable between the two groups.Left atrial area index, left ventricular (LV) end-diastolic, end-systolic and stroke volume indexes, LV mass index, right ventricular end-diastolic and end-systolic volume indexes were significantly higher in the homozygous β°/β° group (see Table).Frequencies of heart failure and arrhythmias were comparable between the groups.No patient showed diabetes or hypoparathyroidism and there was no difference between groups in terms of frequency of hypogonadism or hypothyroidism. Conversely, patients with homozygous β°/β° genotype had a significant higher frequency of osteoporosis (50.0% vs 16.7%; P=0.003). Among patients with osteoporosis, 75% were treated with DFO therapy.Conclusions: Heart remodelling related to a high cardiac output state cardiomyopathy was more pronounced in patients with homozygous β°/β° genotype. Osteoporososis was significantly more frequent in patients with homozygous β°/β° genotype, treated for more than two-thirds with DFO therapy. These data support the knowledge of different phenotypic groups in the management of NTDT patients. [Display omitted] DisclosuresPepe:Chiesi Farmaceutici S.p.A., ApoPharma Inc., and Bayer: Other: No profit support.