Reduced Left Ventricular Contractility Research Articles

The effect of afterload on right ventricular pacing-induced left ventricular dysfunction: a translational study

Abstract Introduction Right ventricular (RV) pacing (RVP) impairs left ventricular (LV) function. Nevertheless, the interaction between arterial afterload and RVP-associated LV dysfunction has not been investigated yet. Purpose We sought to examine the effect of afterload on RVP-evoked LV hemodynamic changes in patients with aortic stenosis (AS) undergoing transcatheter aortic valve implantation (TAVI) as well as in a small animal model of sustained LV pressure overload (PO). Methods Thirty-five patients with AS and a previously implanted pacemaker underwent detailed echocardiographic examination immediately before TAVI and also on the second postoperative day. The ultrasound measurements were carried out during intrinsic, narrow QRS rhythm and during frequency-matched RVP as well. Global myocardial work index (GMWI) was calculated to assess LV contractility. In parallel, LV pressure-volume analysis was performed in Wistar rats with transverse aortic constriction (TAC) or sham operation (Sham) during intrinsic narrow QRS rhythm (termed as TAC-Vsense and Sham-Vsense) as well as during RVP (termed as TAC-Vpace and Sham-Vpace). RVP was achieved in rats by an octopolar electrophysiology catheter placed in the RV. Results RVP decreased LV contractility in AS patients before and after TAVI as well. Nevertheless, the extent of RVP-evoked LV dysfunction was alleviated following pressure unloading (ΔGMWI: -37±7 vs. -25±8%, before TAVI vs. after TAVI, P<0.05). Similarly, although RVP was associated with reduced LV contractility in both the TAC (the slope of the maximum rate of LV pressure rise-end-diastolic volume relation [dPdtmax-EDV]: 92±8 vs. 53±6mmHg/s/µl, TAC-Vsense vs. TAC-Vpace; P<0.05) and Sham groups (dPdtmax-EDV: 74±5 vs. 60±9 mmHg/s/µl, Sham-Vsense vs. Sham-Vpace; P<0.05), the negative inotropic effect of RVP was found to be stronger in the TAC compared to the Sham group (ΔdPdtmax-EDV: -42±4 vs. -19±6%; TAC vs. Sham, P<0.01). Furthermore, reduction of the maximal rate of LV pressure decrease (ΔdPdtmin: -20±3 vs. -5±5%, TAC vs. Sham, P<0.01) and prolongation of the active relaxation time constant (Δτ: 22±3 vs. 6±3%, TAC vs. Sham, P<0.01) also occurred to a greater extent in case of sustained LV PO, indicating augmented diastolic dysfunction. Conclusion Our translational results indicate that RVP-induced LV dysfunction might be afterload dependent.

TCT-639 Immediate Reduction in Left Ventricular Contractility After Mitral Transcatheter Edge-to-Edge Repair Is Associated With Lower Rates of Heart Failure Hospitalizations

TCT-639 Immediate Reduction in Left Ventricular Contractility After Mitral Transcatheter Edge-to-Edge Repair Is Associated With Lower Rates of Heart Failure Hospitalizations

Improved Cardiac Performance and Decreased Arrhythmia in Hypertrophic Cardiomyopathy With Non-β-Blocking R-Enantiomer Carvedilol.

Hypercontractility and arrhythmia are key pathophysiologic features of hypertrophic cardiomyopathy (HCM), the most common inherited heart disease. β-Adrenergic receptor antagonists (β-blockers) are the first-line therapy for HCM. However, β-blockers commonly selected for this disease are often poorly tolerated in patients, where heart-rate reduction and noncardiac effects can lead to reduced cardiac output and fatigue. Mavacamten, myosin ATPase inhibitor recently approved by the US Food and Drug Administration, has demonstrated the ability to ameliorate hypercontractility without lowering heart rate, but its benefits are so far limited to patients with left ventricular (LV) outflow tract obstruction, and its effect on arrhythmia is unknown. We screened 21 β-blockers for their impact on myocyte contractility and evaluated the antiarrhythmic properties of the most promising drug in a ventricular myocyte arrhythmia model. We then examined its in vivo effect on LV function by hemodynamic pressure-volume loop analysis. The efficacy of the drug was tested in vitro and in vivo compared with current therapeutic options (metoprolol, verapamil, and mavacamten) for HCM in an established mouse model of HCM (Myh6R403Q/+ and induced pluripotent stem cell (iPSC)-derived cardiomyocytes from patients with HCM (MYH7R403Q/+). We identified that carvedilol, a β-blocker not commonly used in HCM, suppresses contractile function and arrhythmia by inhibiting RyR2 (ryanodine receptor type 2). Unlike metoprolol (a β1-blocker), carvedilol markedly reduced LV contractility through RyR2 inhibition, while maintaining stroke volume through α1-adrenergic receptor inhibition in vivo. Clinically available carvedilol is a racemic mixture, and the R-enantiomer, devoid of β-blocking effect, retains the ability to inhibit both α1-receptor and RyR2, thereby suppressing contractile function and arrhythmias without lowering heart rate and cardiac output. In Myh6R403Q/+ mice, R-carvedilol normalized hyperdynamic contraction, suppressed arrhythmia, and increased cardiac output better than metoprolol, verapamil, and mavacamten. The ability of R-carvedilol to suppress contractile function was well retained in MYH7R403Q/+ iPSC-derived cardiomyocytes. R-enantiomer carvedilol attenuates hyperdynamic contraction, suppresses arrhythmia, and at the same time, improves cardiac output without lowering heart rate by dual blockade of α1-adrenergic receptor and RyR2 in mouse and human models of HCM. This combination of therapeutic effects is unique among current therapeutic options for HCM and may particularly benefit patients without LV outflow tract obstruction.

FRI500 Atypical Case Of Undifferentiated Shock

Abstract Disclosure: V. Vadini: None. P. Vasistha: None. Introduction: Shock is encountered frequently in the ICU. Undifferentiated shock, however, poses a diagnostic challenge. The differentials and work up are broad and time sensitive. Endocrinopathies are a known etiology but thyroid cardiomyopathy causing cardiogenic shock is rare. Clinical case: A 78 y old man presented to the ER with hypotension that did not improve after administration of 2.5 L IV fluids. Vasopressors were initiated and he was admitted to the ICU. Patient reported 2-month history of generalized weakness, nausea, vomiting, falls and poor oral intake. Review of systems was notable for 20-pound weight loss in 6 months, dyspnea with exertion, loss of appetite and occasional diarrhea. On exam, patient was afebrile, hypotensive 80/40, PR 87, O2 saturation > 90% on room air. He appeared pale with JVP measured at 11 cm of water. Pulse was irregular, heart sounds normal without murmurs. Bilateral lower extremities were mildly edematous. Strength in lower extremities was 4/5 proximal and distally. Labs were notable for normocytic anemia, troponin 1.05, elevated anion gap 18, lactate 1.8, creatinine 3.3 from a baseline of 1 and BNP 1425. ECG showed sinus rhythm with frequent premature atrial contractions. Chest Xray on admission was unremarkable. Additional labs were negative drug screen, normal cortisol, urinalysis. Blood cultures were sent. Overnight, the patient developed tachycardia and atrial fibrillation with rapid ventricular rate. Cardiology was consulted, bedside echo was suspicious for low left ventricular ejection fraction. The patient was anticoagulated with heparin. TSH was sent. He was requiring 2 vasopressors to maintain MAP>65. CT chest abdomen pelvis was unremarkable except stable pulmonary nodule. Patient became hypoxic on Day 2 of admission, CXR now showed features of pulmonary edema. TSH returned less than 0.01, free T4 4.69 Endocrinology was consulted, methimazole was started for thyrotoxicosis. Formal TTE showed LVEF 20-25% with global reduction in left ventricular contractility, dilated left atrium and mild MR. He was given furosemide for pulmonary edema. TSI and TRAB were positive indicating Grave’s disease. He was successfully transferred out of the ICU. Patient gradually became euvolemic with significant improvement in energy, appetite and functional capacity. He was able to participate in physical therapy and was eventually discharged to rehab. Conclusion: This case addresses an uncommon but potentially life-threatening cause of undifferentiated shock. Physical exam, history and high degree of suspicion are key in early identification and treatment. Although thyroid cardiomyopathy is rare, Grave’s disease is common and ruling our thyrotoxicosis should be included in preliminary work up of undifferentiated shock. Presentation: Friday, June 16, 2023

Acausal Modelling of Advanced-Stage Heart Failure and the Istanbul Heart Ventricular Assist Device Support with Patient Data.

In object-oriented or acausal modelling, components of the model can be connected topologically, following the inherent structure of the physical system, and system equations can be formulated automatically. This technique allows individuals without a mathematics background to develop knowledge-based models and facilitates collaboration in multidisciplinary fields like biomedical engineering. This study conducts a preclinical evaluation of a ventricular assist device (VAD) in assisting advanced-stage heart failure patients in an acausal modelling environment. A comprehensive object-oriented model of the cardiovascular system with a VAD is developed in MATLAB/SIMSCAPE, and its hemodynamic behaviour is studied. An analytically derived pump model is calibrated for the experimental prototype of the Istanbul Heart VAD. Hemodynamics are produced under healthy, diseased, and assisted conditions. The study features a comprehensive collection of advanced-stage heart failure patients' data from the literature to identify parameters for disease modelling and tovalidate the resulting hemodynamics. Regurgitation, suction, and optimal speeds are identified, and trends in different hemodynamic parameters are observed for the simulated pathophysiological conditions. Using pertinent parameters in disease modelling allows for more accurate results compared to the traditional approach of arbitrary reduction in left ventricular contractility to model dilated cardiomyopathy. The current research provides a comprehensive and validated framework for the preclinical evaluation of cardiac assist devices. Due to its object-oriented nature, the featured model is readily modifiable for other cardiovascular diseases for studying the effect of pump operating conditions on hemodynamics and vice versa in silico and hybrid mock circulatory loops. The work also provides a potential teaching tool for understanding the pathophysiology of heart failure, diagnosis rationale, and degree of assist requirements.

The left ventricle in well newborns versus those with perinatal asphyxia, haemodynamically significant ductus arteriosus or fetal growth restriction.

Hemodynamic changes accompanying the initial breaths at the time of birth are especially important for a smooth transition of fetal to neonatal circulation. Understanding the normal transitional physiology and the clinical impact of adverse adaptation is important for delineating pathology so as to guide physiologically relevant therapies. Disorders such as severe perinatal asphyxia, hemodynamically significant patent ductus arteriosus (and its surgical ligation) and utero-placental insufficiency underlying fetal growth restriction, can adversely affect left ventricular (LV) function. The left ventricle is the predominant chamber involved in systemic perfusion during postnatal life. Cardiac output is closely linked to afterload; the latter is determined by arterial properties such as stiffness and compliance. This article outlines normal transition in term and preterm infants. It also highlights the adverse impact of three not uncommon neonatal disorders on LV function. Perinatal asphyxia leads to a reduced LV output, superior vena cava and coronary artery blood flow and an increase in the troponin level. Multiple haemodynamic changes are observed in the premature infant with a large patent ductus arteriosus. They need careful analysis to determine when ligation should proceed. Ligation itself generally results in a dramatic increase in afterload which may lead to a reduction in LV contractility and the need for ionotropic support. Fetal growth restricted infants have a higher systolic pressure, a somewhat hypertrophied heart arising from an increased arterial wall thickness/stiffness and systemic peripheral resistance. Point of care ultrasound (POCUS) helps differentiate normal transition and that resulting from neonatal disorders. It may be increasingly utilized in guiding management.

Mitral annular dynamics are influenced by left ventricular load and contractility in an acute animal model.

The purpose of this study was to investigate the effects of loading conditions and left ventricular (LV) contractility on mitral annular dynamics. In 10 anesthetized pigs, eight piezoelectric transducers were implanted equidistantly around the mitral annulus. High-fidelity catheters measured left ventricular pressures and the slope of the end-systolic pressure-volume relationship (Ees ) determined LV contractility. Adjustments of pre- and afterload were done by constriction of the inferior caval vein and occlusion of the descending aorta. Mitral annulus area indexed to body surface area (MAAi ), annular circularity index (ACI), and non-planarity angle (NPA) were calculated by computational analysis. MAAi was more dynamic in response to loading interventions than ACI and NPA. However, MAAi maximal cyclical reduction (-Δr) and average deformational velocity (- ) did not change accordingly (p = 0.31 and p = 0.22). Reduced Ees was associated to attenuation in MAAi -Δr and MAAi - (r2 = 0.744; p = 0.001 and r2 = 0.467; p = 0.029). In conclusion, increased cardiac load and reduced LV contractility may cause deterioration of mitral annular dynamics, likely impairing coaptation and increasing susceptibility to valvular incompetence.

Complications and Mortality after CABG Surgery in Patients with Reduced Ejection Fraction

Coronary artery bypass grafting (CABG) is a complex, high-tech surgical intervention. Its success depends not only on the skill and experience of the surgeon but equally on the coherence of work and professionalism of all services involved in the operation. Severe left ventricular (LV) dysfunction after heart surgery is one of the main causes of cardiogenic shock, which is characterized by a local transient reduction of myocardial contractility (“stunned” myocardium) and/or significant cell damage caused by ischemia. In this state, systemic metabolic disorders often occur: increased concentration of free fatty acids, lactic acidosis, hypoxemia, and increased catecholamine content. General approaches to determining the risk of CABG surgery have not been definitively established. In addition, the data concerning the choice of optimal tactics in patients with a reduced ejection fraction (EF) are still limited. Relatively high early operative mortality in patients with reduced left ventricular EF requires further serious study.
 The aim. To determine the dominant complications and causes of fatal cases in patients with reduced LV contractility after CABG surgery.
 Materials and methods. The study included 210 patients with EF of 35% or less, who underwent CABG at the National Amosov Institute of Cardiovascular Surgery in the period from 01/01/2015 to 12/31/2021. Among them were 190 men (90.5%) and 20 women (9.5%). The age of the patients ranged from 29 to 83 years (61.1±8.9). Most patients underwent revascularization of three or more arteries.
 Results and discussion. In the group of patients with EF 35-30% in the postoperative period, acute heart failure (HF) occurred in 5 (3.8%) cases, respiratory failure (RF) was observed in 3 (2.3%) cases, renal failure in 3 (2.3%) cases, central nervous system (CNS) complications in 5 (3.8%). At the same time, along with the decrease in EF, the frequency of postoperative complications increased. In patients with EF below 24%, the frequency of postoperative complications increased significantly: acute HF was noted in 3 (15%) cases, RF in 5 (25%) cases, renal failure in 2 (10%) cases, CNS complications were noted in 0 (0%) cases. The duration of artificial lung ventilation increased significantly to 24.9±27.7 hours, the length of stay in the intensive care unit increased to 12.8±8 days, and the total length of stay of the patient in the hospital to 20.2±11.7 days.
 Conclusion. Based on the data we received, we concluded that: in patients with reduced LV myocardial contractility, such complications as HF, RF and renal failure, CNS complications most often occur; in addition, their frequency is higher than that in patients with preserved EF and increases with its decrease; one of the most frequent and life-threatening complications in this group of patients was acute HF; the use of intra-aortic balloon pump allows to avoid or improve treatment of HF and, at the same time, to increase survival in patients with reduced LV contractility.

Involvement of Abnormal Gut Microbiota Composition and Function in Doxorubicin-Induced Cardiotoxicity

ObjectivesDoxorubicin (Dox), a chemotherapeutic anthracycline agent for the treatment of a variety of malignancies, has a limitation in clinical application for dose-dependent cardiotoxicity. The purpose of this study was to explore the relationship between the composition/function of the gut microbiota and Dox-induced cardiotoxicity (DIC).MethodsC57BL/6J mice were injected intraperitoneally with 15 mg/kg of Dox, with or without antibiotics (Abs) administration. The M-mode echocardiograms were performed to assess cardiac function. The histopathological analysis was conducted by H&E staining and TUNEL kit assay. The serum levels of creatine kinase (CK), CK-MB (CK-MB), lactic dehydrogenase (LDH), and cardiac troponin T (cTnT) were analyzed by an automatic biochemical analyzer. 16S rRNA gene and metagenomic sequencing of fecal samples were used to explore the gut microbiota composition and function.Key FindingsDox caused left ventricular (LV) dilation and reduced LV contractility. The levels of cardiomyocyte apoptosis and myocardial enzymes were elevated in Dox-treated mice compared with the control (Con) group. 16S rRNA gene sequencing results revealed significant differences in microbial composition between the two groups. In the Dox group, the relative abundances of Allobaculum, Muribaculum, and Lachnoclostridium were significantly decreased, whereas Faecalibaculum, Dubosiella, and Lachnospiraceae were significantly increased compared with the Con group at the genus level. Functional enrichment with Cluster of orthologous groups of proteins (COG) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses showed that the Dox mice displayed different clusters of cellular processes and metabolism from the Con mice. The different species and their functions between the two groups were associated with the clinical factors of cardiac enzymes. Moreover, depletion of the gut microbiota could alleviate Dox-induced myocardial injury and cardiomyocyte apoptosis.ConclusionsThe study here shows that composition imbalance and functional changes of the gut microbiota can be one of the etiological mechanisms underlying DIC. The gut microbiota may serve as new targets for the treatment of cardiotoxicity and cardiovascular diseases.

The emerging role of reassessment of genetic testing results in the diagnosis of the unexplained sudden cardiac arrest's causes

Abstract Background The most common cause of Unexplained Sudden Cardiac Arrest (USCA) are hereditary primary arrhythmic syndromes and subclinical forms of cardiomyopathies. Both of them may be difficult to diagnose. Objective The aim of this study was to re-examine the role of genetic testing in patients after USCA during follow-up. Methods In the years 2014–2017 we studied 44 unrelated patients (pts) (23 men (53%), mean age 36 years) after USCA. All pts underwent cardiac evaluation including ECG, Holter, echo, coronary angiography, stress exercise test and, if necessary cardiac MRI and provocative drug testing. Standard diagnostic criteria were used according to currently available ESC guidelines. We performed next generation sequencing with panel covered coding regions of >4800 genes (26pts), 194 genes (5pts) and whole exome sequencing >2ehab724.3204 genes (5pts). Variants of frequency no greater than 0,001 in existing variants' databases and classified as damaging by at least 3 of applied software algorithms were assessed for pathogenicity according to ACMG standards. The enrolled patients were followed up. During the follow up, the classification of rare variants according to ACMG standards was repeated. Results Based on applicable standards and the clinical data collected, clinical diagnosis was made in 17 (39%) probands (Long QT Syndrome 21%, Brugada Syndrome 7%, Short QT Syndrome 7%, Early Repolarization Syndrome and Catecholaminergic Polymorphic Ventricular Tachycardia 2%, both). Genetic tests were performed in 36 pts. We identified 27 rare variants in 22 pts, in genes associated with inherited arrhythmia or cardiomyopathies, of these 23 rare variants were identified in years 2014–2017. The first classification was in 2017, then only 2 variants (in FLNC) were considered pathogenic and the remaining 21 were classified as Variants of Unknown Significance (VUS). During the years 2019–2021, 23 earlier identified rare variants were reclassified according to The American College of Medical Genetics and Genomics (ACMG) standards, of these 5 VUS became pathogenic/likely pathogenic variants. In addition, we performed genetic tests in next 5 pts – we identified 4 rare variants – 3 pathogenic and 1 VUS. Detection of certain hereditary background of SCA increased from 6,5% in years 2014–2017, to 25% in years 2019–2021. The median follow-up period was 2366 days (interquartile range 1785–2903 days). 17/44 (39%) pts had adequate discharge of ICD. Two pts were observed with reduction of left ventricular contractility and the development of the initial stages of dilated cardiomyopathy. Conclusion This study shows clinical utility of extensive clinical assessment and follow-up of patient after USCA. Routine genetic testing by next generation sequencing in the patients can help in diagnosis and re-evaluation of rare variants should be made during the follow-up. Funding Acknowledgement Type of funding sources: Public Institution(s). Main funding source(s): grant of National Institute of Cardiology, Warsaw, Poland

Heart failure in patients with high homocysteine levels

Increased levels of homocysteine (HHcy) can induce both systolic and diastolic left ventricular (LV) dysfunction that may evolve until chronic heart failure (HF). It is known that HHcy acts as an independent risk factor for atherosclerosis and hypercoagulation. This condition may cause coronary artery disease (CAD. Chronic reduction of oxygen supply to the myocardium can induce a reduction in LV contractility. These conditions can further evolve towards HF with reduced ejection fraction (HFrEF). But, HHcy can be also responsible for adverse cardiac remodeling for accumulation and proliferation of interstitial collagen, increased fibrosis and myocardial stiffness and preserved LV ejection fraction (HFpEF). Both HF can be further favoured by the advanced age, hypertension, diabetes and others. The administration of some nutrients, such as folic acid and B12 vitamin can delay or avoid these cardiac complications. However, the cellular mechanisms behind the adverse effects of Hcy on cardiac remodeling and pump function are not understood.

To Vent or Not to Vent: A Loaded Question During Venoarterial Extracorporeal Membrane Oxygenation Support for Cardiogenic Shock

To Vent or Not to Vent: A Loaded Question During Venoarterial Extracorporeal Membrane Oxygenation Support for Cardiogenic Shock

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.

Ibudilast, a Phosphodiesterase Inhibitor and Toll-Like Receptor-4 Antagonist, Improves Hemorrhagic Shock and Reperfusion-Induced Left Ventricular Dysfunction by Reducing Myocardial Tumor Necrosis Factor α

ObjectivesRapid loss of blood volume causes ischemic injury to myocardial cells and impairs cardiac function. Subsequent reperfusion, although necessary to revitalize stunned tissues, can induce production of reactive oxygen species and inflammation, causing further tissue damages and weakening cardiac function. Ibudilast, a Toll-like receptor-4 (TLR4) antagonist and an inhibitor of phosphodiesterase-4, possesses antioxidative and anti-inflammatory capacities. In this study, we aim to examine the protective efficacy of ibudilast against hemorrhagic shock and reperfusion (HSR)-induced myocardial injury and cardiac dysfunction. MethodsStudies were conducted on male Sprague-Dawley rats in 3 groups: sham-operated, HSR with, and HSR without pretreatment of ibudilast. Hemorrhagic shock was induced by withdrawing blood from the femoral artery until the mean aortic pressure dropped to around 40 mm Hg; reperfusion was conducted by replenishing blood after 120 minutes of hemorrhagic shock, and the observation continued for another 240 minutes. The left ventricular (LV) contractility, diastolic suction capacity, and ventricular stiffness were evaluated using simultaneous LV pressure, and volume was recorded during a temporary inferior vena cava constriction at the end of reperfusion. Ibudilast (10 mg/kg) was administered intraperitoneally 3 days and 20 minutes prior to HSR. Serum creatine kinase myocardial band (CK-MB) was examined at the end of both HSR, and serum CK-MB, myocardial TLR4 protein expression, and malondialdehyde (MDA) and tumor necrosis factor (TNF)-α levels at the end of reperfusion. ResultsHSR induced an increase in serum CK-MB. Subsequent reperfusion further increased serum CK-MB, upregulated myocardial TLR4 protein expression, and increased tissue levels MDA and TNF-α vs the sham (P < .05). HSR reduced LV contractility, prolonged LV relaxation time, and increased LV diastolic stiffness. Ibudilast pretreatment attenuated HSR-induced TLR4 protein expression, reduced myocardial MDA and TNF-α levels, and protected against cardiac dysfunction. ConclusionsIbudilast pretreatment reduced myocardial TLR4 expression, decreased MDA and TNF-α levels, and protected against HSR-induced decrease in LV contractility, prolonged LV relaxation time, and increased diastolic stiffness.

Large mobile left ventricular thrombus in a patient with dilated cardiomyopathy: a case report and review of literature

Dilated cardiomyopathy (DCMP) and the resultant left ventricular (LV) dysfunction are risk factors for thrombus formation in the heart. Once formed, depending on their size, location, and mobility, LV thrombi have the tendency to embolise, sometimes with dire consequences. Early detection and treatment are important to reduce thromboembolic events and in resolution of LV thrombus. Two-dimensional (2D) echocardiography is the most commonly used technique for the diagnosis and follow-up of such cases. Here, we present a case of 30 years old female with DCMP with congestive heart failure (CHF) who developed a large mobile LV thrombus and was managed on anticoagulants to prevent distal embolisation. This case highlights that LV thrombi can even occur in patients in sinus rhythm who have reduced LV contractility.

Prolongation of the Agonal Phase in the DCD Donor Results in Impairment of Myocardial Contractility Following DCD Heart Resuscitation

Purpose Circulatory arrest follows withdrawal of supportive therapy in the DCD donor. The agonal phase following withdrawal can be prolonged and may be associated with hypoxia and hypotension. Our aim was to evaluate the impact of the duration of the agonal period on the capacity for cardiac resuscitation. Methods Rats (n = 6/group) were subjected to hypoventilation using a mechanical ventilator and exposed to either brief (5 mins), moderate (30 mins) or prolonged (60 mins) hypoxia and hypotension prior to circulatory arrest. This method was used to simulate an agonal phase of varying duration. Following circulatory arrest 15 minutes of warm ischemia was observed prior to reperfusion with extracorporeal membrane oxygenation (ECMO). ECMO reperfusion was followed by cardiac resuscitation. Load independent left ventricular (LV) contractility was assessed at baseline and following resuscitation via the end-systolic pressure volume relationship (ESPVR). Results Hypoventilation was followed by a decrease in oxygen saturation (pre 96% vs post 48%), mean arterial pressure (pre 72 +/- 14 vs. post 41 +/- 5 mm Hg) and pH (pre 7.49 +/- 0.1 vs. post 6.99 +/- 0.1). There was no difference between groups in LV contractility at baseline. Following circulatory arrest and cardiac resuscitation all groups demonstrated a decline in contractile function from baseline. There was marked reduction in LV contractility in animals with a 60-minute agonal phase (ESPVR: 60 minutes; 0.17 +/- 0.08, 30 minutes; 0.66 +/- 0.16, 5 minutes; 0.47 +/- 0.09, p Conclusion Brief or moderate exposure to hypoxia and hypotension prior to circulatory arrest was associated with satisfactory recovery of contractile function. Prolonged exposure to these conditions was associated with a significant decline in LV contractility. In the human DCD donor marked prolongation of the agonal phase may limit cardiac donation.

198 Heart failure increases mitochondrial s-nitrosylation

Heart failure affects over 5 50 000 people living in the United Kingdom (1) and roughly half of those present with reduced cardiac ejection fraction (2). The electron transport chain...

Blood pressure reduction after gastric bypass surgery is explained by a decrease in cardiac output.

The reason for the decrease in blood pressure (BP) in the first weeks after gastric bypass surgery remains to be elucidated. We show that the reduction in BP following surgery is caused by a decrease in cardiac output. In addition, the maximal ascending slope in systolic blood pressure decreased suggesting a reduction in left ventricular contractility and cardiac workload. These findings help to understand the physiological changes following gastric bypass surgery and are relevant in light of the increased risk of heart failure in these patients.

The Effects of Experimental Sleep Apnea on Cardiac and Respiratory Functions in 6 and 18 Month Old Dystrophic (mdx) Mice.

Duchenne muscular dystrophy (DMD) is a fatal disease where over 90% of patients succumb to respiratory or cardiac failure. Sleep apnea and sleep disordered breathing (SDB) are noted in a plurality of DMD patients, and the resulting nocturnal episodic hypoxia (EH) cannot be ruled out as a contributing factor to cardiac and respiratory dysfunction. In this study, we investigated the impact of long-term episodic hypoxia, which mimics the cyclic hypoxia seen in sleep apnea, on cardiac and respiratory function in a murine model of DMD (mdx mice). Since the severity and prevalence of sleep apnea in DMD increases with age, we studied the impact of EH on young (6-month) and on older (18-month) mdx mice. Mice were either exposed for 12 weeks to EH (8 hours/day, 5 days/week) or to room air. We noted a significant increase in left ventricular (LV) dilatation (transthoracic echocardiography) on EH exposure in both age groups, but reduced LV contractility was seen only in 6-month old mice. With EH exposure, an increased fibrosis (hydroxyproline) was noted in both cardiac and diaphragm muscle in 18-month but not 6-month old mice. No significant change in relative diaphragm strength (in-vitro) was noted on EH exposure in 18-month old mice. In contrast, EH exposed 6-month old mice showed a significant increase in relative diaphragm strength. EH exposure did not result in any significant change in ventilatory parameters (barometric plethysmography) in awake 6-month old mdx mice. In contrast, 18-month old mdx mice showed considerable ventilatory dysfunction, consistent with reduced ventilatory reserve. Our findings highlight that sleep apnea impacts respiratory and cardiac function in muscular dystrophy, and that EH can have divergent effects on both systems. To our knowledge, this is the first comprehensive study to investigate the impact of EH on cardiac and respiratory function in mdx mice.

Abstract 19128: Acute Changes in Left Ventricular Contractility Following Mitraclip Implantation Depend on Left Atrial Volume

Background: The acute hemodynamic changes following elimination of mitral regurgitation is a much discussed issue, particularly in patients with severely compromised left ventricular function where the incompetent mitral valve was regarded as a pop-off valve. Herein, we investigated the acute changes of ventricular contractility in relation to left atrial volume. Methods and results: Echocardiographic left atrial and left ventricular longitudinal strain measurements before and 3 days after the procedure were performed in 19 patients (mean age: 77.9±7.9, 47% female, 73,7% functional mitral valve regurgitation, 26,3% degenerative mitral valve regurgitation) undergoing MitraClip implantation at our institution. Procedural success with reduction in MR to grade 2+ or less was achieved in all patients. Overall there was no significant change in left atrial or ventricular global or regional longitudinal strain after the procedure. However, a strong correlation was observed between worsening in left ventricular strain and left atrial volume (r: -0.72, p&lt;0.01), i.e. there was a greater reduction in left ventricular contractility after clip implantation in patients with larger left atrial volumes. Multivariate, linear regression analyses revealed that left atrial volume predicted the change of left ventricular longitudinal strain following MitraClip implantation (r2: -0.07, p&lt;0.01) independently of left ventricular ejection fraction (r2: -0.05, p=0.40), mitral regurgitant volume (r2: -0.09, p=0.09) and left atrial strain (r2: -0.03, p=0.85). Discussion: Our data suggest that enlarged left atria act as a low-resistance reservoir in mitral regurgitation. As a consequence elimination of mitral regurgitation in these patients leads to worsening of left ventricular contractility whereas in smaller atria left ventricular contractility is not negatively affected by elimination of MR.