Ventricular Volume Overload Research Articles

2020 ACC/AHA Guideline for the Management of Patients With Valvular Heart Disease: A Report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines.

2020 ACC/AHA Guideline for the Management of Patients With Valvular Heart Disease: A Report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines.

Abstract 14952: Hemodynamic Comparison of Left Ventricular Function in Pressure Overload- versus Volume Overload-Induced Heart Failure Models by Invasive Pressure-Volume Analysis

Introduction: Both sustained left ventricular (LV) pressure overload (PO) and volume overload (VO) induces LV remodeling and eventually development of heart failure (HF). Using rat models, the present study aimed to provide a detailed comparison of distinct aspects of LV function in PO- and VO-induced HF. Methods: PO and VO was induced by transverse aortic constriction (TAC, n=12) and aortocaval shunt (AV-shunt, n=12) creation respectively. Controls underwent corresponding sham operations (n=11). LV remodeling was characterized by echocardiography, histology, qRT PCR, and western blot. LV function was assessed by invasive pressure-volume (P-V) analysis. Results: Both sustained PO and VO resulted in the development of HF, as evidenced by increased LV BNP mRNA expression, pulmonary edema, and characteristic symptoms. While the extent of LV hypertrophy was comparable between the HF models, PO induced concentric while VO evoked eccentric LV remodeling. P-V analysis revealed impaired systolic function in both HF models. Accordingly, decreased ejection fraction and impaired ventriculo-arterial coupling (calculated as the ratio of arterial elastance/LV contractility [VAC]: 0.38±0.05 vs. 1.30±0.13, ShamTAC vs. TAC and 0.52±0.08 vs. 1.17±0.13, ShamAV-Shunt vs. AV-shunt; p<0.05) was detected in both HF models. However, in case of VO the severely reduced LV contractility (slope of end-systolic P-V relationship: 1.79±0.19 vs. 0.52±0.06, ShamAV-Shunt vs. AV-shunt, p<0.05 and 2.14±0.28 vs. 2.03±0.21, ShamTAC vs. TAC p>0.05) underpinned the contractility-afterload mismatch, while in case of PO the increased afterload (arterial elastance: 0.77±0.07 vs. 2.64±0.28, ShamTAC vs. TAC and 0.80±0.07 vs. 0.54±0.05, ShamAV-Shunt vs. AV-shunt; p<0.05) was the main determinant. Furthermore, prolongation of active relaxation occurred to a greater extent in case of PO. In addition, increased myocardial stiffness was only observed in PO-induced HF. Conclusion: Systolic function was reduced in both HF models. However, different factors underpinned the impaired VAC in case of VO (reduced LV contractility) and PO (increased arterial elastance). Furthermore, although diastolic function deteriorated in both models, it occurred to a greater extent in case of PO.

Risk factors for severe pulmonary regurgitation after repair of tetralogy of Fallot with transannular patch.

Severe pulmonary regurgitation may result in right ventricular volume overload and decreased right ventricular function. Severe pulmonary regurgitation can be predicted prior to repair of tetralogy of Fallot. The aim of this study was to determine the risk factors for severe pulmonary regurgitation in repaired tetralogy of Fallot with transannular patch. This was a cross-sectional study in 43 patients with repaired tetralogy of Fallot using transannular patch. This study was carried out in Dr. Cipto Mangunkusumo hospital during 2015 to 2018. Participants were followed up for routine examination using echocardiography. We used bivariate and multivariate logistic regression using STATA 12.1 to identify risk factors for severe pulmonary regurgitation in this population. A total of 43 patients composed of 22 boys and 21 girls with repaired tetralogy of Fallot using transannular patch were enrolled in the study. Median age of participants was 6 years at admission (2.1-18.5 years) and 3.4 years (1-17 years) at repair. Median length of follow-up was 2.1(1-4.3) years. Risk factors associated with severe pulmonary regurgitation after tetralogy of Fallot repair were McGoon ratio > 1.8 (odds ratio = 6.9; 95% confidence interval = 1.6-30) and follow-up duration >1.9 years (odds ratio = 3.6; 95% confidence interval = 0.9-15.2). McGoon ratio > 1.8 and follow-up duration > 1.9 years are associated with severe pulmonary regurgitation after tetralogy of Fallot repair.

Renal Outcomes Following Left Ventricular Assist Device Placement: A Single Center Experience

Introduction Renal dysfunction is a prognostic factor in morbidity and mortality after left ventricular assist device (LVAD) placement. As a result, poor renal function often affects a patient's eligibility for LVAD implantation. However, in some, cardiac output augmentation following LVAD placement may improve renal perfusion. The extent of change in renal function and predictors of long-term renal function post-LVAD implantation have not been well studied. Methods This retrospective cohort included consecutive patients who underwent LVAD implantation (HeartMate[HM] II and HM3) between 2008-2018 at a single center for both bridge-to-transplant and destination therapy (DT) indications. We examined the relationship of clinical parameters with changes in renal function 6 months post-LVAD. Glomerular filtration rate (GFR) was calculated using Modification of Diet in Renal Disease Study equation. We performed multivariable logistic regression analyses to determine predictors of decreased renal function. Results We examined 91 patients (mean age 59.7± 13.2, female 11%, HM II 89%, DT 68%). Post-LVAD, 52 patients (57.1%) improved and 39 (42.9%) had deterioration in renal function (Table). Among all patients, 16 (17.6%) had more than 25% reduction in GFR, 6 (6.6%) had a post-LVAD GFR of less than 30 mL/min/1.73 m2, and 2 (2.2%) developed end stage renal disease (ESRD) requiring dialysis. Of those patients who had improved GFR post-LVAD, 30 (57.7%) had more than 25% improvement in their GFR. Among patients who had a GFR 25% reduction in GFR (OR: 3.96, 95% CI 1.4 - 13.8), p=0.03). None of the other clinical parameters listed in the Table were associated with worse renal outcomes. Pre-LVAD GFR was also not predictive of >25% post-implant GFR reduction or the development of ESRD. Conclusion Renal function may improve after LVAD placement. In patients with long-term decreased renal function post-LVAD, the reduction in GFR was rarely severe. Elevated RA pressure, a marker of right ventricular dysfunction and volume overload, is potential predictor of poor renal outcomes after LVAD placement.

Echocardiographic Changes in Chronic Kidney Disease Patients on Maintenance Hemodialysis

IntroductionChronic kidney disease (CKD) carries a significant association with cardiac diseases, which suggests a minor reduction in the glomerular filtration rate (GFR) can act as an independent risk factor for causing cardiovascular abnormalities. Patients of CKD having cardiovascular disease (CVD) had three to thirty times higher risk of mortality as compared to the general population. In addition, mortality among cardiovascular patients has been found to be twofold higher in CKD stage 2 patients and three-fold higher in patients with stage 3 CKD, when collated to patients with normal renal function. Furthermore, cardiomyopathy among hemodialysis (HD) is due to the presence of coronary artery obstruction, reduction in coronary reserves, and left ventricular (LV) physiological-structural abnormalities secondary volume and pressure overload. Echocardiography is a gold standard diagnostic modality for the identification of cardiac structural and functional abnormalities. Therefore, the evaluation of echocardiographic parameters in patients of CKD can help to determine the risk and prognosis of CVD in patients of CKD. In the present study, we evaluated the echocardiographic findings in patients of CKD on maintenance hemodialysis.MethodsThis cross-sectional study was conducted in the nephrology unit of Jinnah Postgraduate Medical Center between March 2019 to October 2019. A total of 100 patients who were on maintenance for more than one year were included in the analysis. Two-dimensional transthoracic echocardiography was done in each patient for the determination of cardiac structural and functional parameters such as LV hypertrophy, LV systolic dysfunction, and LV diastolic dysfunction.ResultsThe mean age of the patients was 46.9±12.8 years. There was male dominance with male/female ratio 63/37. There were 39% hypertensive and 62% anemic patients. LV dysfunction was diagnosed in 31% of patients, LV diastolic dysfunction in 47% patients, and left ventricular hypertrophy (LVH) in 55% of patients. LVH was found in 74.3% hypertensive patients versus only 42.6% non-hypertensive patients (p-value 0.001). LV systolic dysfunction was also high in hypertensive patients, 46.1% versus 21.3% patients in non-hypertensive patients (p-value 0.008). ConclusionThere is a high frequency of cardiac functional and structural abnormalities in CKD patients on HD especially in patients having concomitant hypertension. LVH is the most common structural defect and LV diastolic dysfunction is the most common functional cardiac defect in CKD patients on hemodialysis.

Serum Level of Heart Type Fatty Acid Binding Protein Before and after Treatment of Congestive Heart Failure in Children

Background: Heart failure (HF) in children is a clinical and pathophysiological syndrome that results from ventricular dysfunction, volume or pressure overload, either alone or in combination. This study aimed to estimate serum level of H-FABP before and after treatment of congestive heart failure, and correlate its level with severity of the disease. Patients and methods: The study was cohort control study. It included 30 infants and children; their ages ranged from two months to four years with heart failure diagnosed clinically and were admitted to Cardiology Unit of Pediatric Department, at Zagazig University Hospitals during the period from November 2017 to April 2018. They were divided into four groups, first group aged (2-12 month), second group (13-24 m), third group (25-36 m) and fourth group (37-48 m). Echocardiographic assessment of the heart was done using conventional Doppler echocardiography. Serum heart type fatty acid binding protein (H-FABP) level (estimated on patient admission and 1 week after treatment) was determined by quantitative sandwich enzyme linked immunosorbent assay (ELISA) technique. Results: There was a significant difference in the serum level of H-FABP in our patients before treatment (2.156 ± 1.156 ng/ml) compared with after treatment (0.882 ± 0.716 ng/ml). There was a significant positive correlation between serum H-FABP level and Ross classification. Conclusion: H-FABP may be used as diagnostic and prognostic predictor of adverse outcome in children with heart failure.

Serum Level of Heart Type Fatty Acid Binding Protein Before and after Treatment of Congestive Heart Failure in Children

Background: Heart failure (HF) in children is a clinical and pathophysiological syndrome that results from ventricular dysfunction, volume or pressure overload, either alone or in combination. This study aimed to estimate serum level of H-FABP before and after treatment of congestive heart failure, and correlate its level with severity of the disease. Patients and methods: The study was cohort control study. It included 30 infants and children; their ages ranged from two months to four years with heart failure diagnosed clinically and were admitted to Cardiology Unit of Pediatric Department, at Zagazig University Hospitals during the period from November 2017 to April 2018. They were divided into four groups, first group aged (2-12 month), second group (13-24 m), third group (25-36 m) and fourth group (37-48 m). Echocardiographic assessment of the heart was done using conventional Doppler echocardiography. Serum heart type fatty acid binding protein (H-FABP) level (estimated on patient admission and 1 week after treatment) was determined by quantitative sandwich enzyme linked immunosorbent assay (ELISA) technique. Results: There was a significant difference in the serum level of H-FABP in our patients before treatment (2.156 ± 1.156 ng/ml) compared with after treatment (0.882 ± 0.716 ng/ml). There was a significant positive correlation between serum H-FABP level and Ross classification. Conclusion: H-FABP may be used as diagnostic and prognostic predictor of adverse outcome in children with heart failure.

Galectin-3 as a Biomarker of Heart Failure in Children with Congenital Heart Disease

Background: Heart failure is defined as a clinical and pathophysiologic syndrome results from ventricular dysfunction, volume, or pressure overload, alone or both. Galectin-3 is a novel biomarker that mediates fibrosis in many organs like the heart that interest in galactin3 as a potential heart failure biomarker that reflects ongoing ventricular remodeling. Objective: To see if galectin-3 acts as a biomarker of heart failure in congenital heart disease and evaluate if there is a correlation between galectin-3 and severity of HF detected by Ross classification and echocardiogram. Patients and Methods: The present study included 38 cases with HF due to CHD admitted to PICU and pediatric department at Zagazig University Hospital from July 2018 to July 2019. Patients were selected to exclude heart failure other than congenital heart disease. Results: Galectin-3 level was significantly higher in children with CHD than age and sex-matched healthy children. There were statistically significant positive correlations between Galectin 3 and ROSS so higher Galectin-3 levels were associated with measures of HF severity. The level was significantly elevated in children with HF in comparison to those without HF, with a significant correlation with the disease severity. Galectin 3 had sensitivity 80%, specificity 100%, PPV 100% and PPN 71.4%. Conclusion: Galectin-3 has short term prognosis and can be used as a tool to help in HF diagnosis in children as a marker of disease severity (positive correlation between Ross classification and galectin-3 serum level was proved) and staging patients with acute HF due to congenital heart diseases.

Increasing carbohydrate oxidation improves contractile reserves and prevents hypertrophy in porcine right heart failure

In heart failure, myocardial overload causes vast metabolic changes that impair cardiac energy production and contribute to deterioration of contractile function. However, metabolic therapy is not used in heart failure care. We aimed to investigate the interplay between cardiac function and myocardial carbohydrate metabolism in a large animal heart failure model. Using magnetic resonance spectroscopy with hyperpolarized pyruvate and magnetic resonance imaging at rest and during pharmacological stress, we investigated the in-vivo cardiac pyruvate metabolism and contractility in a porcine model of chronic pulmonary insufficiency causing right ventricular volume overload. To assess if increasing the carbohydrate metabolic reserve improves the contractile reserve, a group of animals were fed dichloroacetate, an activator of pyruvate oxidation. Volume overload caused heart failure with decreased pyruvate dehydrogenase flux and poor ejection fraction reserve. The animals treated with dichloroacetate had a larger contractile response to dobutamine stress than non-treated animals. Further, dichloroacetate prevented myocardial hypertrophy. The in-vivo metabolic data were validated by mitochondrial respirometry, enzyme activity assays and gene expression analyses. Our results show that pyruvate dehydrogenase kinase inhibition improves the contractile reserve and decreases hypertrophy by augmenting carbohydrate metabolism in porcine heart failure. The approach is promising for metabolic heart failure therapy.

Detection of atrial shunt lesions with asingle echocardiographic parameter.

SummaryBackgroundUnrepaired left to right atrial shunt lesions can cause significant right ventricular (RV) volume overload. The parameter pulmonary to systemic shunt volume ratio (Qp:Qs) has been shown to detect even small differences between left and right ventricular stroke volume; however, four parameters are needed for its calculation. This study was carried out to evaluate the accuracy of the single parameter right ventricular outflow tract (RVOT) velocity time integral (VTI) to identify atrial shunt lesions.MethodsAll patients who underwent transesophageal echocardiography (TEE) examination at this institution between 1 January 2013 and 1 January 2018 were retrospectively analyzed. The RVOT-VTI was measured in the transthoracic echocardiography performed immediately before each TEE. The diagnostic accuracy for detection of atrial shunt lesions was tested.ResultsA total of 2797 patients with a median age of 67 years (interquartile range, IQR 54–77 years) were included in the final analysis. A total of 113 (4%) patients had a relevant atrial shunt lesion. The mean RVOT-VTI of the shunt group was 25 cm (SD ± 8.1 cm) and was significantly higher than that of the non-shunt group with 17 cm (SD ± 4.8 cm) (p < 0.001). The area under the curve (AUC) was 0.81. A total of 106 patients (93.8%) of the shunt group had a VTI of ≥16 cm. If the RVOT-VTI was <16 cm, the negative predictive value was 99.3%. If the RVOT-VTI was ≥25 cm, 22% of patients proved to have a significant shunt lesion.ConclusionIn this large retrospective analysis it could be shown that a low RVOT-VTI predicted the absence of significant atrial shunt lesions, while a high RVOT-VTI predicted the presence. The parameter should be applied in all patients with suspected atrial shunt lesions where calculation of Qp:Qs is impossible.Electronic supplementary materialThe online version of this article (10.1007/s00508-020-01659-0) contains supplementary material, which is available to authorized users.

The Natural and Unnatural History of Ventricular Septal Defects Presenting in Infancy: An Echocardiography-Based Review

Ventricular septal defect (VSD), the most common congenital heart defect, accounts for 40% of heart malformations. Despite this prevalence, there remains no consensus on the utility of echocardiography to guide modern-era treatment. In this study, we evaluated patients with isolated VSDs to test the hypothesis that echocardiographic evidence of left ventricular (LV) volume overload and type of VSD are associated with surgical intervention and to identify useful echocardiographic indicators for management of VSDs in infants and children. We reviewed 350 patients with VSDs diagnosed during the first year of life. Echocardiographic measurements were made at the time of diagnosis and at the endpoint. The VSD area was calculated using inner edge to inner edge dimensions obtained from two planes and indexed to body surface area. Aortic annulus dimension, left atrium to aortic root ratio, LV end-diastolic diameter, left atrial volume, VSD velocity-time integral, ejection fraction, and pulmonary to systemic blood flow ratio (Qp:Qs) were measured using conventional methods. One hundred seventy-seven muscular (50.5%) and 162 perimembranous (46%) VSDs accounted for the vast majority of defects. Only seven (4%) muscular defects required surgical closure, while 76 (47%) perimembranous defects required surgery. Indexed VSD area, VSD to aortic valve ratio, indexed left atrium volume, LV end-diastolic diameter, VSD velocity-time integral, and Qp:Qs at diagnosis were significantly different between the surgical and nonsurgical groups. Ventricular septal defect area > 50mm2/m2 at initial diagnosis was independently associated with risk for surgery (P=.0055). Indexed VSD area is an echocardiographic variable that can be easily measured at diagnosis and can provide insight into the likelihood of requiring surgical intervention regardless of the type and location of the defect.

Circulating Forms of B-Type Natriuretic Peptide in Very Preterm Infants.

B-type natriuretic peptide (BNP) is a cardiac hormone released with an N-terminal fragment (NTproBNP) under conditions of ventricular pressure or volume overload. BNP has been proposed for use as a biomarker of cardiac dysfunction in premature infants in the setting of hemodynamically significant patent ductus arteriosus (HsPDA) and bronchopulmonary dysplasia (BPD). In adult settings the presence of proBNP and glycosylated isoforms may affect assay interpretation. However, there are limited data on how immature preterm physiology may affect BNP or NTproBNP levels and no published data on post-translational BNP processing in premature infants. Pooled serial plasma samples from preterm infants born at less than 30 weeks gestation were analyzed for BNP congeners using Luminex® assay and high performance liquid chromatography. Samples were grouped according to clinical status: Group 1, no HsPDA and no BPD, Group 2 HsPDA and no/mild BPD, Group 3 HsPDA and moderate/severe BPD. Plasma from 15 infants was analyzed, and across all three groups NTproBNP predominated with minimal amounts of other isoforms; no glycosylation was detected. NTproBNP appears to be the predominant isoform across each of our clinical groups in our pooled sample analysis with no evidence of significant glycosylation. This suggests NTproBNP is likely to be a robust marker in this clinical setting.

P718 Unexpected finding during follow up for a suspected arrythmogenic right ventricular cardiomyopathy (ARVC)

Abstract Interatrial communication is the most common congenital defect found in adulthood, being the most common ostium secundum variety (70-80%). Superior and inferior sinus venosus defects are less usual, found in the 5-10% of cases of interatrial communication and frequently associated with anomalous pulmonary venous return (APVR). These defects are located near the junction of the superior (5%) or inferior (&amp;lt;1%) vena cava with the right atrium, which makes them difficult to diagnose by transthoracic ecocardiography (TTE). Case description: A 44-year-old man who is being followed up in our electrophysiology consulting with suspicion of ARVC (suggestive CMR with no gene found) after an episode of ventricular tachycardia (VT) 11 years ago. Asymptomatic since then under treatment with atenolol, except for an episode of chest pain that required a coronary computed tomography which described an image compatible with a patent foramen ovale and normal coronary arteries. During the follow-up a cardio magnetic resonance (CMR) is performed which showed a severely dilated right ventricle with diskinetic areas, no volume changes since last CMR (5 years ago) and preserved ejection fraction. A small interatrial communication located infero-posteriorly in the septum drawed our attention. Estimated QP/QS was 1.4. After this finding, we reviewed the CT made 4 years ago, where a flow from the left atrium to the right atrium could be seen. We decided to ask for both a transthoracic echocardiography (TTE) and a transesophageal echocardiography (TEE). TTE showed normal left ventricle, a dilated right ventricle with preserved function, no valvulopathies and normal pulmonary pressure. Shunt test with agitated saline was slightly positive after Valsalva maneuver, and QP/QS was again 1.4. TTE showed a small interatrial communication measuring 1.9x0.8cm, next to inferior vena cava`s drainage. Since right ventricle dilation could be due both to the atrial septal defect (ASD) and to the dysplasia, the case was discussed in the heart team, and as the defect was small, QP/QS was 1.4 and pulmonary pressure was normal we adopted a conservative approach. Inferior sinus venosus defects are one of the least common atrial septal defects. They are located in the atrial septum immediately above the orifice of the inferior vena cava and are often associated with partial anomalous connection of the right pulmonary veins. This location makes it difficult to see by means of a common TTE or TEE, and usually as in our case multimodal approach can be very helpful. Usually patients with this kind of atrial septal defect (ASD), signs of significant shunt (right ventricular volume overload, QP/QS≥1.5) and systolic PA pressure less than 50% of systemic pressure (with pulmonary vascular resistance less than one third of the systemic vascular resistance) are suggested for surgery. In this case the possibility of two pathologies overlapping makes it challenging for diagnosis and treatment. Abstract P718 Figure. Multimodal imaging for diagnosis.

P1729 Abnomral course of pulmonary vein causing right heart dilatation

Abstract Funding Acknowledgements None Introduction Partial anomalous pulmonary venous return is a rare congenital cardiac anomaly that usually involves the right pulmonary vein and an atrial septal defect. It is accounted for 0.7%. Isolated partial anomalous pulmonary venous return with an intact atrial septum is even rarer, and this condition is usually treated surgically in younger patients. We report a case of a young female, incidentally found to have a right upper pulmonary vein draining into the right atrium, confirmed by TOE and CT Venography pulmonary, with moderate right ventricular enlargement, without pulmonary hypertension, intra-cardiac shunt or accompanied congenital anomaly. A decision of surgical correction was made. We conclude that it is important to suspect PAPVC in patients with right ventricular volume overload, even in absence of ASD. Case presentation A 26-year-old female, not known to have any chronic illness. She was referred because of poor appetite and low weight, to cardiology evaluation for accidental murmur finding during examination. She had no other symptoms. The TOE was done which showed left pulmonary veins are normal, the right lower pulmonary vein is normal, and there is high suspicion of aberrant right upper pulmonary vein draining in the right atrium, no evidence of intra-cardiac shunt. CT Venography pulmonary revealed anomalous (Giant) right superior pulmonary vein to the superior vena cava and draining to the right atrium. Figure 1. Patient was referred for surgical correction. Discussion Partial anomalous pulmonary venous return is a type of left to right shunt. It is a rare congenital abnormal cardiac defect in which the pulmonary veins draining into the right atrium (RA) directly or indirectly by venous connection. Its accounted for 0.4 to 0.7%. However, as this rate is based upon autopsy data, the true prevalence of PAPVR may actually be higher. PAPVR is frequently associated with other congenital heart disease, most commonly ASD, in &amp;gt;75% of patients. It is estimated that 10% to 15% of patients with ASD and up to 85% of patients with sinus venosus ASD have PAPVC. Exclusive of ASD, other more complex cardiac malformations occur in ∼20% of patients. PAPVR can also be an isolated defect with intact atrial septum. TOE is more sensitive than TTE in detecting PAPVR. A potential limitation of echocardiography is the availability of acoustic windows. If all four PVs are not identified emptying into the left atrium on TEE, CCT and CMR may provide complementary data . CONCLUSION In conclusion, missed diagnosis always occurs in PAPVR, the debauched and blood flow of pulmonary vein should be over-viewed carefully during TEE examination. In a patient with unexplained RV enlargement PAPVC (one or more pulmonary veins) should be considered in the differential diagnosis. Multi-modality cardiac imaging using echocardiography, CT angiography and CMR may provide a comprehensive noninvasive evaluation of PAPVC. Abstract P1729 Figure. Fig1 TOE (Top),CT (Bottom) of RUPV

Abnormal left ventricular flow organization following repair of tetralogy of Fallot

BackgroundLeft ventricular intracavitary flow (LVICF) characteristics reflect diastolic function. Right ventricular (RV) volume overload due to pulmonary regurgitation (PR) adversely impacts interventricular interactions and left ventricular (LV) function. This aimed to determine whether patients with PR and mild to moderate RV dilation after repair of tetralogy of Fallot (TOF) repair have abnormal LVICF, and to determine whether RV dilation and biventricular function correlate with LVICF abnormalities. MethodsPatients with repaired TOF with PR (n = 11) and controls (n = 11) underwent LVICF analysis. LV end-diastolic volume was partitioned into 4 flow components: direct flow, retained inflow, delayed ejection flow, and residual volume. Flow components were correlated with indexed biventricular size, function, and LV strain. ResultsThe TOF patients had reduced direct flow (35% vs 25%; P = .004) and increased residual volume (15% vs 24%; P = .026) compared with controls. Retained inflow and delayed ejection flow did not differ. Reduced direct flow correlated with increased RV end-diastolic volume index (R = 0.44; P = .042), RV end-systolic volume index (R = −0.46; P = .032), reduced RV ejection fraction (R = 0.45; P = .036), and reduced LV circumferential strain (R = 0.52; P = .014). Increased residual volume correlated with increased RV end-systolic volume index (R = 0.52; P = .013), reduced LV ejection fraction (R = −0.54; P = .010), and reduced LV circumferential strain (R = −0.44; P = .040). ConclusionsPatients with repaired TOF with mild to moderate RV dilation have abnormal LV diastolic direct flow and increased recirculating residual volume. These changes correlate with the degree of RV dilation and impaired LV function.

P1833The c-fos mRNA expression reveals persistent myocardial stretch in the right ventricle during asphyxiated cardiac arrest

Abstract Background Donation after circulatory death (DCD) heart transplantation has been debated over the past decades because of the shortage of donor. The right ventricular dysfunction is one of the remaining problems for clinical implication of DCD heart transplantation. DCD hearts suffering from the volume overload have a potential to aggravate the right ventricular dysfunction after heart transplantation. The c-fos mRNA is one of the “immediate” response genes to mechanical stresses, such as myocardial cell stretch, without neural and humoral factors. In this study, we assessed myocardial stretch during asphyxiated cardiac arrest using c-fos mRNA expression. Purpose The purpose of this study is to reveal the impact of right ventricular volume overload during asphyxiated cardiac arrest. Methods Male Wistar rats (8 weeks of age, n=18) were anesthetized with paralyzed ventilation. The trachea was dissected and ligated to initiate asphyxiation. Hearts were harvested at 3 time points: 0, 15 and 30 minutes after termination of the ventilation. Free walls of right and left ventricle were sectioned and immersed in RNA stabilization solution as soon as possible. Total RNA was extracted from these tissues using a guanidine thiocyanate-phenol-chloroform method and cDNA was synthesized using a reverse transcriptase. Next, we measured the quantified expression level by using the droplet digital PCR method with a probe and primers for c-fos gene. Expression of c-fos level was divided by extracted TATA binding protein (TBP) level as a control marker, the ratio of c-fos and TBP was used in analysis. Results In the left ventricle, the expression of c-fos rapidly increased by 15 minutes (0.81±0.24 (c-fos/TBP), p&lt;0.05 by one-way ANOVA followed by the Dunnett's test) compared to at 0 minutes (0.21±0.06), but the expression level recovered to the baseline level at 30 minutes after termination of the ventilation (0.19±0.03). On the other hand, in the right ventricle, the c-fos expression was gradually elevated and peaked at 30 minutes (0.88±0.20, p&lt;0.05 by the Dunnett's test) compared to at 0 minutes (0.22±0.05). Conclusion These results suggest that the volume overload to the right ventricle during asphyxiated cardiac arrest prolongs compared to that to the left ventricle, which may cause the right ventricular dysfunction after DCD heart transplantation.

Chronic Severe Aortic Regurgitation: Should We Lower Operating Thresholds?

Chronic Severe Aortic Regurgitation: Should We Lower Operating Thresholds?

Abstract 861: Inner Mitochondrial Collapsing in Response to Acute Overstretch of Rat Ventricular Papillary Muscles

Introduction: The effect of acute ventricular volume overload on organelles such as myofibrils and mitochondria are incompletely understood. Purpose: We performed acute overstretch on cardiac papillary muscle to investigate the functional and morphological changes. Methods: We used male SD-rats (10-12 weeks old) and dissected papillary muscles from the right ventricle. A papillary muscle preparation was stretched to Lmax. We overstretched it within 2 seconds up to 110% of Lmax (110%Overstretch; 110%OS) or 120% of Lmax (120%OS), and stimulated it (1Hz, 36°C) with tension measurement, compared with Lmax group. After the measurement of tension, we analyzed the morphological changes in muscle fibers and organelles using a Transmission electron microscopy (TEM). Results: The active tension after overstretch was immediately decreased to 67.8±3.8% in 110%OS, and to 17.3±4.0% in 120%OS. In TEM study, muscle fibers kept their well-organized structures and the sarcomere length was stretched to 2.4 μm in 110%OS, and to 2.6 μm in 120%OS. In contrast, in 110%OS, inner mitochondrial density was lower than that in Lmax, indicating swelled mitochondria. In 120%OS, inner mitochondrial empty space with vacuolation was found in the large area of myocardium, indicating that inner mitochondria cristae were susceptible to mechanical stress-induced deterioration. Conclusions: Acute overstretch of rat papillary muscles causes inner mitochondrial collapsing with preserved the sarcomere structure. It could account for the mechanisms of acute volume-overloaded heart failure.

Physiological and Clinical Consequences of Right Ventricular Volume Overload Reduction After Transcatheter Treatment for Tricuspid Regurgitation

ObjectivesThis study sought to examine the impact of chronic right ventricular (RV) volume overload and implications of tricuspid regurgitation (TR) reduction on biventricular function. BackgroundSevere TR is a major determinant of adverse outcomes in advanced heart failure patients. The understanding of TR pathophysiology and implications of correction is still limited. Transcatheter tricuspid edge-to-edge repair (TTVR) is a new treatment option in patients at high surgical risk and provides a unique pathophysiological model without confounding effects of cardiac surgery. MethodsTwenty-nine patients (78 ± 4 years of age) with severe isolated TR and high surgical risk underwent TTVR using the MitraClip system, and of these 18 underwent repeated cardiac magnetic resonance. Clinical follow-up was realized at 1 and 6 months after the intervention. ResultsTR fraction was reduced from 41% to 21% (p < 0.01) without increase in RV afterload (p = 0.52) and RV end-diastolic volume (p < 0.01), and RV stroke volume decreased (p = 0.03), whereas RV effective forward flow increased (p = 0.03). Left ventricular (LV) filling improved with an increase in LV end-diastolic volume (p = 0.01) and LV stroke volume (p = 0.02), leading to an augmentation of cardiac indices (2.2 ± 0.6 l/min/m2 vs. 2.7 ± 0.6 l/min/m2; p < 0.01) with similar results at 6 months follow-up. After TTVR, New York Heart Association functional class significantly improved (p < 0.01), peripheral edema decreased (p = 0.01), and 6-min walk distance increased by 20% and 22% after 1 and 6 months, respectively (p < 0.01). ConclusionsTTVR reduces chronic RV volume overload without increase in RV afterload, improves RV performance and LV filling, and enhances cardiac output. These changes translate into symptomatic and functional improvement. These implications for biventricular physiology and clinical status are maintained at 6 months follow-up.

SUN-224 N-TERMINAL PRO-B-TYPE NATRIURETIC PEPTIDE IS A PREDICTOR OF CHRONIC KIDNEY DISEASE INCIDENCE IN AN ASIAN GENERAL POPULATION:THE OHASAMA STUDY

N-terminal pro-B-type natriuretic peptide (NT-proBNP) is a screening marker for heart failure. A previous study demonstrated the positive association between NT-proBNP level and chronic kidney disease (CKD) incidence in individuals aged ≥65 years in the United States. As no report has described the relationship between NT-proBNP level and CKD incidence in Asian populations, we investigated this in the Japanese population. We followed up 867 participants without CKD, history of cardiovascular disease, and atrial fibrillation from the general population of Ohasama, Japan. We defined CKD as an estimated glomerular filtration rate (eGFR) of <60 mL/min per 1.73 m2 and/or proteinuria. The primary outcome was defined as CKD incidence determined during the annual checkups from 2002 to 2014. In accordance with previous studies, the participants were classified into four groups according to NT-proBNP level (<30.0, 30.0–54.9, 55.0–124.9, and ≥125.0 pg/mL). NT-proBNP was measured by using an electrochemiluminescence immunoassay (Roche Diagnostics, Tokyo, Japan). The Cox proportional hazards model was applied to assess adjusted hazard ratios (HRs) for CKD incidence after adjustment for sex, age, body mass index, current smoking status, alcohol consumption, diabetes mellitus, hypercholesterolemia, history of cardiovascular disease, systolic blood pressure, use of antihypertensive drugs, and eGFR at baseline. The participants’ mean age was 59.1 years, and 587 (67.7%) were women. The median (interquartile range) NT-proBNP level was 41.3 pg/mL (23.5–70.0 pg/mL). During the mean follow-up period of 9.7 years, 177 participants developed CKD. When we used the group with NT-proBNP levels of <30.0 pg/mL as reference, the adjusted HRs (95% confidence interval) for CKD incidence in the 30.0-54.9, 55.0-124.9, and ≥125.0 pg/mL groups were 1.34 (0.90–2.01), 1.25 (0.81–1.92), and 1.83 (1.05–3.18), respectively. Natural log-transformed (ln) NT-proBNP was also associated with the risk of CKD (HR [95% confidence interval] per 1-SD increase in lnNT-proBNP (1.30 [1.05–1.61]). Although we performed the stratification analyses according to age, sex, baseline eGFR, use of hypertensive medication, or hypertension for the risk of CKD, no significant interactions were observed between these factors and lnNT-proBNP for the risk for CKD (interaction P ≥ 0.33). The lowest HR per 1-SD increase in lnNT-proBNP was observed in the participants aged <65 years (HR [95% confidence interval] per 1-SD increase in lnNT-proBNP: 1.06 [0.75–1.49]). The present study demonstrated for the first time the association between NT-proBNP level and elevated risk of CKD in an Asian population. The participants with NT-proBNP levels of ≥125.0 pg/mL had a higher CKD risk than those with NT-proBNP levels of <30.0 pg/mL in the present study. This suggests that NT-proBNP can be a significant predictor of CKD incidence in Asian populations. NT-proBNP level is enhanced by ventricular wall stretch or volume overload, which is related to venous congestion. Venous congestion results in renal dysfunction. Moreover, elevated NT-proBNP levels suggest the reduced clearance rate caused by subclinical renal dysfunction because renal excretion is the main route of clearance for NT-proBNP. NT-proBNP level is not only a screening marker for heart failure but also a predictive indicator of kidney prognosis.