Myocardial Recovery Research Articles

Beyond hot flashes: Exploring the role of estrogen therapy in postmenopausal women for myocardial infarction prevention and recovery.

Myocardial infarction (MI) commonly known as "heart attack" results from the blockage of blood flow to the heart. Postmenopausal women face an elevated risk of MI due to declining estrogen levels, a hormone pivotal in maintaining cardiovascular health. It promotes vasodilation, reduce inflammation, and improves lipid profiles. While estrogen therapy shows promise in mitigating MI risk for postmenopausal woman, its efficacy in prevention and recovery remains a subject of debate. This review provides a critical assessment of existing evidence on estrogen therapy's cardioprotective effects for postmenopausal women. It delves into estrogen's role in vascular function enhancement, inflammation reduction, and lipid metabolism modulation. Additionally, it addresses the various forms of estrogen therapy, administration methods, dosage considerations, safety implications, and associated risks. The review highlights the existing controversies and knowledge gaps related to estrogen therapy for MI prevention. It underscores the urgency for in-depth research to decipher the nexus between estrogen therapy and MI risk, especially concerning primary prevention and specific postmenopausal subgroups. Future studies should investigate optimal formulations, doses, and administration routes of estrogen therapy as well as assess treatment timing and duration. Comparative studies and long-term follow-up are necessary to inform clinical decision-making and improve patient care. Addressing these research gaps will empower clinicians to make more judicious choices about estrogen therapy for MI prevention and recovery in postmenopausal women, aiming for enhanced patient outcomes.

Assessment of Autophagy Markers Suggests Increased Activity Following LVAD Therapy

Left ventricular reverse remodeling in heart failure is associated with improved clinical outcomes. However, the molecular features that drive this process are poorly defined. Left ventricular assist devices (LVADs) are the therapy associated with the greatest reverse remodeling and lead to partial myocardial recovery in most patients. In this study, we examined whether autophagy may be implicated in post-LVAD reverse remodeling. We found expression of key autophagy factors increased post-LVAD, while autophagic substrates decreased. Autolysosome numbers increased post-LVAD, further indicating increased autophagy. These findings support the conclusion that mechanical unloading activates autophagy, which may underly the reverse remodeling observed.

Re-Dosing del Nido cardioplegia in adult cardiac surgery: Perfusion characteristics and outcomes--Is there an optimal redosing strategy?

del Nido cardioplegia is utilized for myocardial protection in adult patients undergoing cardiac surgery; however, no standardized re-dosing protocol exists. We describe perfusion characteristics and clinical outcomes in adult cardiac surgery patients who were re-dosed with del Nido cardioplegia. Chart review was performed for adult patients undergoing cardiac surgery (specific inclusion/exclusion criteria below) who received exactly two doses of del Nido cardioplegia from 2012 to 2019; n = 542 patients. The main outcome was a composite endpoint comprised of operative mortality, myocardial infarction, post-operative cardiac support device (CSD), and postoperative decrease in ejection fraction (EF), which was analyzed via multivariable logistic regression (MVLR). A secondary analysis evaluated postoperative vasoactive-inotropic scores (VIS) via gamma log link regression (GLLR) as a more physiologic indication of myocardial recovery. MVLR demonstrated that increased total cardiopulmonary bypass (CPB) time was associated with a positive composite outcome (p < .001), whereas time between doses (p = .237) and the volume of each dose was not (p = .626). GLLR also demonstrated that prolonged CBP, decreased EF, congestive heart failure at time of surgery, and low hematocrit at the start of the surgery were all associated with higher VIS. In this retrospective study, variations in re-dosing strategy for del Nido cardioplegia do not affect postoperative outcomes and increased CPB time is associated with increased operative mortality, myocardial infarction, need for post-operative CSDs, and reduced postoperative EF, and increased VIS, irrespective of the re-dosing strategy. Further studies are warranted to to identify additional patient and operative characteristics that predispose to complications.

Acute aerobic exercise regulation of myocardial calcium homeostasis involves CASQ1, CASQ2, and TRDN.

Exercise maintains cardiac calcium homeostasis and promotes cardiovascular health. This study explored temporal changes of calcium-related myocardial transcriptome changes during the recovery phase following a single bout of moderate-intensity aerobic exercise. Healthy male Sprague-Dawley rats were anesthetized with sodium pentobarbital after moderate-intensity aerobic exercise at four time points (0, 12, 24, and 72 h postexercise). The hearts were removed and RNA-seq and bioinformatics analyses were used to examine temporal transcriptional changes in the myocardium. Casq1, Casq2, and Trdn were identified as key genes in the regulation of calcium homeostasis during myocardial recovery. The highest expression of Casq1, Casq2, and Trdn genes and the proteins they encode occurred 24 h after exercise. An in vitro calcium overload heart model using the Langendorff heart perfusion method was used to examine myocardial calcium buffering capacity. Calcium overload caused the least changes in left ventricular developed pressure, infarct area, Lactate dehydrogenase release, and extent of morphological damage to myocardial cells, with the highest protein expressions of CASQ1, CASQ2, and TRDN at 24 h after acute exercise. This study indicates that maximal myocardial Ca2+ buffering capacity occurs 24 h postexercise in rats. Our study provides insights into exercise-mediated improvements in cardiovascular function and exercise preconditioning.NEW & NOTEWORTHY Acute aerobic exercise upregulates myocardial Casq1, Casq2, and Trdn genes and the proteins they encode in rats. Higher protein levels of CASQ1, CASQ2, and TRDN conferred an improved ability of the myocardium to resist calcium overload. Furthermore, 24 h postexercise is the time point with optimal myocardial calcium buffer capacity.

Myocardial Recovery, Metabolism, and Structure after Cardiac Arrest with Cardioplexol.

Clinical studies indicate encouraging cardioprotective potential for Cardioplexol. Its cardioprotective capacities during 45 minutes of ischemia compared with pure no-flow ischemia or during 90 minutes of ischemia compared with Calafiore cardioplegia were investigated experimentally. Forty-four rat hearts were isolated and inserted into a blood-perfused pressure-controlled Langendorff apparatus. In a first step, cardiac arrest was induced by Cardioplexol or pure no-flow ischemia lasting 45 minutes. In a second step, cardiac arrest was induced by Cardioplexol or Calafiore cardioplegia lasting 90 minutes. For both experimental steps, cardiac function, metabolic parameters, and troponin I levels were evaluated during 90 minutes of reperfusion. At the end of reperfusion, hearts were fixed, and ultrastructural integrity was examined by electron microscopy. Step 1: after 90 minutes of reperfusion, hearts exposed to Cardioplexol had significantly higher left ventricular developed pressure (CP-45': 74%BL vs. no-flow-45': 45%BL; p = 0.046) and significantly better maximal left ventricular relaxation (CP-45': 84%BL vs. no-flow-45': 51%BL; p = 0.012). Oxygen consumption, lactate production, and troponin levels were similar in both groups. Step 2: left ventricular developed pressure was lower (22 vs. 48% of BL; p = 0.001) and coronary flow was lower (24 vs. 53% of BL; p = 0.002) when Cardioplexol was used compared with Calafiore cardioplegia. Troponin I levels were significantly higher under Cardioplexol (358.9 vs. 106.1 ng/mL; p = 0.016). Cardioplexol significantly improves functional recovery after 45 minutes of ischemia compared with pure ischemia. However, Cardioplexol protects the myocardium from ischemia/reperfusion-related damage after 90 minutes of ischemia worse than Calafiore cardioplegia.

Heart Failure with Recovered Ejection Fraction in Patients with Vinculin Loss-of-function Variants

Predictors of myocardial recovery in heart failure (HF) are poorly understood. We explored if vinculin (VCL) variants are associated with myocardial recovery in dilated cardiomyopathy (DCM). Six infants with DCM with a VCL loss-of-function (LOF) variant were identified. Median age at diagnosis was 2 months, median LV ejection fraction was 24%, and median LV end-diastolic diameter z-score was 10.8. All patients received HF medications. Five patients (83%) showed normalization of LV function at a median age of 2.7 years. One patient progressed to end-stage HF requiring heart transplant. This case series identified a unique phenotype of HF with reduced ejection fraction at presentation that evolved to HF with recovered EF in over 80% of infant DCM cases with LOF VCL variants. These findings have prognostic implications for counseling and management of VCL-associated DCM and highlight a possible genetic basis for HF with recovered ejection fraction.Graphical abstract

LVAD therapy as a catalyst to heart failure remission and myocardial recovery.

The management of chronic heart failure over the past decade has witnessed tremendous strides in medical optimization and device therapy including the use of left ventricular assist devices (LVAD). What we once thought of as irreversible damage to the myocardium is now demonstrating signs of reverse remodeling and recovery. Myocardial recovery on the structural, molecular, and hemodynamic level is necessary for sufficient recovery to withstand explant and achieve sustained recovery post-LVAD. Guideline-directed medical therapy and unloading have been shown to aid in recovery with the potential to successfully explant the LVAD. This review will summarize medical optimization, assessment for recovery, explant methodologies and outcomes post-recovery with explant of durable LVAD.

Study of predictors of low cardiac output syndrome after cardiac valve surgery

Objective: Low cardiac output syndrome (LCOS) is defined as a decrease in cardiac index (CI) &lt;2.0L/min/m2 and systolic blood pressure &lt;90mmHg, accompanied by signs of a tissue hypoperfusion (cool peripheries, clammy skin, altered mental status, reduced urine output, elevated serum lactate levels) and the need for medication or mechanical circulatory support to improve hemodynamics [4,7]. LCOS is one of the serious complications after open cardiac surgery with a rate of 2-14% depending on the patient and the risk of death increases 12-25 times [3]. Besides modern equipment, early detection and timely treatment reduce mortality as well as increase myocardial recovery. LCOS prognostic factors play an important role. The aim of this study is to identify the prognostic signs of LCOS after valvular surgery.&#x0D; Subjects and methods: A cross-sectional descriptive study on patients undergoing valvular heart surgery at the Cardiovascular Anesthesiology Department - Cardiovascular Center - Hue Central Hospital from February 2022 to July 2022. LCOS is the dependent variable and the independent variable was divided into three groups before surgery, during surgery and after surgery. The data were processed by software R4.2.2. Using univariate logistic regression to identify independent prognostic factors. &#x0D; Results: A study on 60 patients after heart valve surgery showed that: LCOS after heart valve surgery has a rate of 28.3% with an average time of 5.88 hours after surgery. Through univariate logistic regression analysis, the results found independent prognostic factors including: EF &lt;=40% at preoperative time points (OR=12.9, 95%CI 1.73 – 26.5), EF 0h (OR) =2.3, 95%CI 2.4-8.9), EF 4h (OR=2.9, 95%CI 1.9-6.7), EF 24h (OR=1.9, 95%CI 1.5-9.5), lactate at 0h postoperative time (OR=1.81, 95%CI 1.25-2.8), 4h (OR=1.41, 95%CI 1.13-1.85), 8h (OR=1.38, 95%CI 1.14-1.73), 12h (OR=1.35, 95%CI 1.11-1.72), creatinine at 24 h after surgery (OR=1.02, 95%CI 1.01-1.04), time to extracorporeal circulation (OR=1.02, 95%CI 1.02-1.04), time to clamp aorta (OR=1.2, 95%CI 1.1-1.2).[1]&#x0D; Conclusion: Low cardiac output syndrome is one of the serious complications after heart valve surgery, early detection and timely treatment reduce the risk of death for patients. The study showed that many factors before, during and after surgery are independent prognostic factors for LCOS after surgery.

Evaluating Indices for Non-invasive Myocardial Recovery Assessment in LVAD-Supported Heart Failure Patients.

Accurate assessment of myocardial recovery (MR) under left ventricular assist device (LVAD) support is essential for clinicians to manage heart failure patients. However, current techniques for assessing MR are time-consuming, invasive, and infrequent. Measuring MR using indices derived from LVAD operating data instead provides a potential real-time alternative. Several of these indices for assessing the MR of LVAD-supported heart failure patients were collated from the literature and subject to a comprehensive comparative analysis. The objective of this analysis was to determine the most accurate index for assessing systolic cardiac function under LVAD-support, characterized by maximal end-systolic elastance (Emax), while remaining insensitive to preload & afterload. The indices were compared in computational simulation, utilizing an LVAD + cardiovascular system model to sweep through a large array of Emax and resistance conditions. Results demonstrated the index that correlated best with Emax, showing the highest accuracy, was the ratio between maximum flow acceleration and flow pulsatility (average R2 =0.9790). The same index also exhibited the lowest % variation (sensitivity) to preload & afterload (1.32% & 13.53% respectively). However, opportunities for improvement remain among current recovery assessment indices, with this study providing a baseline of performance for potential future indices to improve upon.Clinical relevance- This study presents a potential real-time measure of native cardiac function in LVAD-supported heart failure patients to support patient management and further recovery.

Left Ventricular Assist Device explantation using a new double patch technique.

There are several surgical approaches for explantation of an LVAD after recovery of cardiac function. Thus, remaining ventricular assist device components may bear significant risks of infection or thrombosis. We hereby report our technique and two-center experience with explantation of LVADs using a new double patch technique. From March 2019-April 2021, 5 patients underwent LVAD explantation after myocardial recovery (HVAD, n = 2; HeartMate 3, n = 3). Mean patient age was 50.3 years (100% male) and mean time on LVAD was 23.1 ± 20.8 months. Primary heart failure aetiology was dilated cardiomyopathy (n = 4) and myocarditis (n = 1).LVAD explantation was performed using a median sternotomy and cardiopulmonary bypass. The LVAD was stopped, and the outflow graft clamped. The outflow graft was ligated and sutured close to the aortic anastomosis. The driveline was clipped and removed. Under induced fibrillation, the attachment of the LVAD was released from the apical cuff and the LVAD was removed. A round pericardial patch was fixed from the inner of the ventricle. This already seals the apex of the heart. An additional Goretex patch is continuously sutured epicardially over the suture ring. The 5 cases showed technically uncomplicated explantation of the LVADs. During the follow-up of mean 16.4 ± 16.9 months, survival of 100% was observed. There were no bleeding complications or thromboembolic events during follow-up. LVAD explantation with the double patch technique is feasible and safe. This technique allows discontinuation of anticoagulation. There was a 30-day survival of 100%. Further studies are needed to provide better evidence for LVAD explantation and long-term follow-up.

Myocardial recovery following left ventricular assist device implantation.

Durable left ventricular assist devices (LVADs) have consistently shown improved mortality and morbidity in patients with end-stage heart failure. Select patients with LVADs may experience significant enough myocardial recovery after device implantation to allow for explantation or decommissioning. While earlier trials suggested a high incidence of recovery, real-world clinical data have demonstrated this to be a much rarer phenomenon. Whether or not patients experience recovery, practices such as speed optimization and usage of guideline-directed medical therapy can improve patient outcomes.

Natural shear waves show sequential changes in myocardial stiffness In paediatric multi-inflammatory systemic syndrome post COVID

Abstract Funding Acknowledgements Type of funding sources: Private grant(s) and/or Sponsorship. Main funding source(s): Egyptian ministry of research and higher education Background Multi-inflammatory systemic syndrome post COVID infection (MIS-C) in children causes myocarditis and affects myocardial diastolic function. Recent high frame rate echocardiography allows to assess myocardial shear waves (SW). SW are mechanical waves generated by mitral and aortic valve closure (MVC &amp; AVC). Their propagation velocities are related to myocardial stiffness (MS), a determinant of diastolic function. Nevertheless, this has not yet been tested in paediatric cardiology and in this pathology. Purpose This study aimed at exploring the changes in natural SW propagation velocity as measure of myocardial diastolic properties in paediatric patients with MIS-C. Methods Seven MIS-C children (mean age 6.7 ±3.6 years) were prospectively followed over 6 months (group A). As a control group; one hundred-four healthy volunteers (HV) (mean age 10.2 ±4.4 years) were recruited (group B). High-frame rate echocardiography was used to obtain parasternal long axis views of all subjects at a frame rate of 1580 ±113 Hz. An anatomical M-mode was drawn along the interventricular septum and Tissue Doppler acceleration maps were extracted to measure SW propagation speed after MVC and AVC (Figure 1). Independent sample t-test was used to compare between both groups. Repeated measures analysis of variance (ANOVA) was used to show sequential changes during follow-up. Results SW propagation velocities were significantly higher among MIS-C patients than in HV group after both MVC (4.3 ±0.6 m/s vs 2.8 ±0.3 m/s respectively, p&amp;lt;0.001) and AVC (5.2 ±0.6 m/s vs 3.0 ±0.3 m/s respectively; p&amp;lt;0.001). Interestingly, SW propagation speeds in MIS-C patients declined significantly with myocardial recovery during course of disease (figure 2) and normalised 6 months post discharge (MVC: 2.9 ±0.3 m/s; P&amp;lt;0.001, AVC: 3.2 ±0.4 m/s; P&amp;lt;0.001) compared to admission. Conclusions SW speed found to be 1.5 to 1.7 fold higher with myocardial inflammation in MIS-C patients compared to HV. Values normalised within 6 months. These findings indicate that SW velocities can show sequential changes in the course of a disease and suggest that SW imaging has potential to serve as a new non-invasive diagnostic tool in paediatric cardiac diseases.

Indipendent predictors of akinetic segment recovery during dobutamine infusion assessed by cardiac magnetic resonance

Abstract Funding Acknowledgements Type of funding sources: None. Background Myocardial viability assessment can guide myocardial revascularization in patients with coronary artery disease. Non-invasive imaging modalities are routinely used for detection of viable myocardium and the highest diagnostic performance is provided by Cardiac Magnetic Resonance (CMR): it combines high sensibility (95%) by delayed enhancement (DE) assessment and high specificity (91%) by evaluation of myocardial systolic thickening recovery at increasing dose of dobutamine (Db-systolic recovery). Purpose Identification of independent predictors for Db-systolic recovery of akinetic segments supplied by a chronic total occlusion (CTO) coronary artery. The second purpose was to develop a diagnostic tool as alternative to dobutamine stress imaging to provide an estimation of myocardial response to inotropic agents. Methods This single center prospective observational study enrolled 47 consecutive patients referred to CMR for evaluation of inducible ischemia and myocardial viability in the territory of one or more CTOs. All enrolled patients presented basal akinetic segments in the CTO territory. Cine-Steady State Free Precession (SSFP) sequences were acquired both in basal and at increasing dose of dobutamine to evaluate Db-systolic recovery. Stress perfusion imaging and DE were then acquired to detect inducible ischemia and necrotic areas. Post-processing CMR-Feature Tracking strain analysis provided both radial and circumferential strain on basal, mid and apical short axis planes. Results Table 1 lists clinical characteristics of the study population. A total of 189 akinetic segments supplied by a CTO were detected and divided into viable and non-viable groups according to their ability to recover or not at increasing dose of dobutamine, respectively. Parameters of each akinetic segment significantly (p value &amp;lt; 0.05) associated with viability at univariate analysis were included in the multivariable binary logistic regression to identify independent predictors of Db-systolic recovery (Table 2). These independent predictors have been then included in a logistic regression model as continuous variable except for Transmural Extent of DE which can be either 1 or 0 according to DE&amp;lt;75% or ≥75%, respectively: L= −5.459 + 0.033 * (Radial Peak Systolic Strain) + 0.067 * (Circumferential Endocardial Peak Systolic Strain) + 1.808 * (Transmural Extent of DE) + 0.358 * (Diastolic Wall Thickness). When L ≥ 0 the model predicts contractile recovery during dobutamine infusion with an accuracy of 83.1%. Conclusion This CMR prospective study identifies independent predictors of contractile recovery at increasing dose of dobutamine and provides a diagnostic tool which might substitute dobutamine assessment with a good accuracy, reducing acquisition time and adverse events in patients with CTOs. An external validation study is needed to assess the consistency of this model for clinical purposes.

Longitudinal Assessment of Left Ventricular Function in Patients with Myopericarditis After mRNA COVID-19 Vaccination.

Multiple reports have described myopericarditis following mRNA COVID-19 vaccination. However, data on the persistence of subclinical myocardial injury assessed by left ventricular (LV) longitudinal strain (LVLS) is limited. Our aim was to assess LV function longitudinally in our cohort of COVID-19 vaccine-related myopericarditis using ejection fraction (EF), fractional shortening (FS), LVLS, and diastolic parameters. Retrospective, single-center review of demographic, laboratory, and management data was performed on 20 patients meeting diagnostic criteria for myopericarditis after mRNA COVID-19 vaccination. Echocardiographic images were obtained on initial presentation (time 0), at a median of 12 days (7.5, 18.5; time 1), and at a median of 44 days (29.5, 83.5; time 2). FS was calculated by M-mode, EF by 5/6 area-length methods, LVLS by utilization of TOMTEC software, and diastolic function by tissue Doppler. All parameters were compared across pairs of these time points using Wilcoxon signed-rank test. Our cohort consisted predominantly of adolescent males (85%) with mild presentation of myopericarditis. The median EF was 61.6% (54.6, 68.0), 63.8% (60.7, 68.3), 61.4% (60.1, 64.6) at times 0, 1, and 2, respectively. Upon initial presentation, 47% of our cohort had LVLS < -18%. The median LVLS was -18.6% (-16.9, -21.0) at time 0, -21.2% at time 1 (-19.4, -23.5) (p = 0.004) and -20.8% (-18.7, -21.7) at time 2 (p = 0.004, as compared to time 0). Though many of our patients had abnormal strain during acute illness, LVLS improved longitudinally, indicating myocardial recovery. LVLS can be used as marker of subclinical myocardial injury and risk stratification in this population.

Impact of Impella protected-percutaneous coronary intervention on left ventricle function recovery of patients with extensive coronary disease and poor left ventricular function

BackgroundThe use of Impella support is increasingly adopted to “protect” patients with severe coronary artery disease (CAD) and left ventricle (LV) dysfunction undergoing percutaneous coronary intervention (PCI). AimsTo evaluate the impact of Impella-protected (Abiomed, Danvers, Massachusetts, USA) PCIs on myocardial function recovery. MethodsPatients with significant LV dysfunction undergoing multi-vessel PCIs with pre-intervention Impella implantation were evaluated by echocardiography before PCI and at median follow up of 6 months: global and segmental LV contractile function were assessed by LV ejection fraction (LVEF) and wall motion score index (WMSI), respectively. Extent of revascularization was graded using the British Cardiovascular Intervention Society Jeopardy score (BCIS-JS). Study endpoints were LVEF and WMSI improvement, and its correlation with revascularization. ResultsA total of 48 high surgical risk (mean EuroSCORE II 8) patients with median LVEF value of 30%, extensive wall motion abnormalities (median WMSI 2.16), and severe multi-vessel CAD (mean SYNTAX score 35) were included. PCIs brought a significant reduction of ischemic myocardium burden with BCIS-JS decrease from mean value of 12 to 4 (p < 0.001). At follow-up, WMSI reduced from 2.2 to 2.0 (p = 0.004) and LVEF increased from 30% to 35% (p = 0.016). WMSI improvement was proportional to the baseline impairment (R − 0.50, p < 0.001), and confined to revascularized segments (from 2.1 to 1.9, p < 0.001). ConclusionsIn patients with extensive CAD and severe LV dysfunction, multi-vessel Impella-protected PCI was associated to an appreciable contractile recovery, mainly determined by regional wall motion improvement in revascularized segments.

Human-umbilical cord matrix mesenchymal cells improved left ventricular contractility independently of infarct size in swine myocardial infarction with reperfusion.

Human umbilical cord matrix-mesenchymal stromal cells (hUCM-MSC) have demonstrated beneficial effects in experimental acute myocardial infarction (AMI). Reperfusion injury hampers myocardial recovery in a clinical setting and its management is an unmet need. We investigated the efficacy of intracoronary (IC) delivery of xenogeneic hUCM-MSC as reperfusion-adjuvant therapy in a translational model of AMI in swine. In a placebo-controlled trial, pot-belied pigs were randomly assigned to a sham-control group (vehicle-injection; n = 8), AMI + vehicle (n = 12) or AMI + IC-injection (n = 11) of 5 × 105 hUCM-MSC/Kg, within 30 min of reperfusion. AMI was created percutaneously by balloon occlusion of the mid-LAD. Left-ventricular function was blindly evaluated at 8-weeks by invasive pressure-volume loop analysis (primary endpoint). Mechanistic readouts included histology, strength-length relationship in skinned cardiomyocytes and gene expression analysis by RNA-sequencing. As compared to vehicle, hUCM-MSC enhanced systolic function as shown by higher ejection fraction (65 ± 6% vs. 43 ± 4%; p = 0.0048), cardiac index (4.1 ± 0.4 vs. 3.1 ± 0.2 L/min/m2; p = 0.0378), preload recruitable stroke work (75 ± 13 vs. 36 ± 4 mmHg; p = 0.0256) and end-systolic elastance (2.8 ± 0.7 vs. 2.1 ± 0.4 mmHg*m2/ml; p = 0.0663). Infarct size was non-significantly lower in cell-treated animals (13.7 ± 2.2% vs. 15.9 ± 2.7%; Δ = -2.2%; p = 0.23), as was interstitial fibrosis and cardiomyocyte hypertrophy in the remote myocardium. Sarcomere active tension improved, and genes related to extracellular matrix remodelling (including MMP9, TIMP1 and PAI1), collagen fibril organization and glycosaminoglycan biosynthesis were downregulated in animals treated with hUCM-MSC. Intracoronary transfer of xenogeneic hUCM-MSC shortly after reperfusion improved left-ventricular systolic function, which could not be explained by the observed extent of infarct size reduction alone. Combined contributions of favourable modification of myocardial interstitial fibrosis, matrix remodelling and enhanced cardiomyocyte contractility in the remote myocardium may provide mechanistic insight for the biological effect.

SHOCK4: Utilizing Mechanical Circulatory Support and Immunomodulation for the Management of Fulminant Lymphocytic Myocarditis: Case Series

Purpose: Five consecutive patients with biopsy-proven lymphocytic myocarditis (LM) presented to our medical center with cardiogenic shock (CS) requiring Mechanical Circulatory Support (MCS) and Immunomodulatory therapy. We present our experience and highlight the variability of presentation and management strategies. Methods: Five consecutive patients presented to our center between 3/1/2022 and 12/1/2022 with acute onset ventricular dysfunction and CS (Table). One had an out-of-hospital cardiac arrest. Due to the fulminant presentation and lack of typical risk factors, there was high clinical suspicion for myocarditis. One patient had positive influenza A testing. Results: All patients were managed acutely with VA-ECMO with or without left ventricular ventilation. All patients underwent an endomyocardial biopsy which showed virus-negative LM. Immunomodulatory therapy strategies varied among patients. Our initial approach was Methylprednisolone for 3 days and IVIG for all. Moreover, for those with a slower rate of recovery, or continued high inflammatory markers, plasmapharesis was utilized in addition to prolonged prednisone and/or azathioprine courses (Table). Of the five subjects, two had myocardial recovery, one developed chronic myocarditis, one developed chronic heart failure, and one required a durable LVAD. Conclusion: Lymphocytic myocarditis is a rare inflammatory disorder of the heart characterized by mononuclear cellular infiltrate and ventricular dysfunction. Fulminant myocarditis is characterized by CS or cardiac arrest. Prompt diagnosis is critical because the prognosis and recovery are better than with nonspecific histological findings or giant cell myocarditis (1,2). Our series and others have demonstrated MCS key role in decreasing mortality while treating the myocardial consequences of inflammatory injury (5-7). While viral infections are the most common cause found in 30-40% of cases (1,3,4), only one patient in our series had an influenza A infection, and none had positive viral testing on the biopsy. We found no consistent history of COVID-19 infection or vaccination among the patients. There is no consensus on the best strategy for immunomodulatory therapy, and more extensive studies with long-term outcomes are needed.

P50: Heart and Kidney Transplant and Recovery after Left Ventricular Assist Device and Intermittent Hemodialysis: Systematic Review and Individual-Participant-Data Meta-analysis

Background: Patients with left ventricular assist devices (LVADs) who require chronic intermittent dialysis (iHD) are considered to have poor prognosis despite paucity of supportive evidence, most of which is limited to case reports and very small single-center cohorts. This systematic review and individual-participant-data meta-analysis aims to study the main outcomes of patients receiving iHD during durable LVAD support, including heart, kidney, and heart-kidney transplantation (HT, KT, HKT, respectively) and mortality. Methods: We retrieved citations from ClinicalTrials.gov, Cochrane, Embase, PubMed, and Web of Science through systematic searches. We selected cohort studies (with n ≥5) of patients who were started on iHD at any point during durable LVAD support, excluding patients who exclusively received continuous renal replacement therapy but no actual iHD. We conducted Kaplan-Meier survival estimations and graphs, and compared mortality data between groups using the Gehan-Breslow-Wilcoxon test. P <.05 was considered statistically significant. We did not pursue inputations for missing data. Results: Six studies with a total of 64 patients met selection criteria. Their median age was 57.5 (46-64.5) years, 49 (76.6%) were men, 46 (86.8%) patients had a HeartMate (HM) 2, whereas 5 (9.4%) had a HM3, and 2 (3.8%) had an HVAD. Twenty-eight (66.7%) patients had LVADs as bridge to HT, and 14 (33.3%) as destination therapy. Only 26 (65%) were reported to have a history of CKD. Patients were initiated on iHD at a median of 18 (7-48) days after LVAD implantation, and remained on iHD for 68 (36-185) days. Eleven (17.2%) patients received HT, and at least 1 additional patient achieved myocardial recovery with LVAD explantation. Four (4.3%) patients became recipients of HKT, including one patient who had recovered enough of their renal function as to stop needing iHD prior to transplantation. Twenty-seven (42.2%) experienced renal recovery. Thirty-one (48.4%) patients died at 103 (64-308) days after initiation of iHD. According to Kaplan-Meier survival calculations, median survival was estimated at 153 (SE 217.5; CI 65-835) days (Figure 1). Survival after initiation of iHD was statistically significantly longer for patients who received HT (mortality: 2 [6.4%] vs 16 [11.6%]; p=.0346; median survival: 1972 [SE 98.8; 799-] days vs 93 [SE 10.3; CI 57-404] days), as evidenced in Figure 2. Survival comparisons between groups stratified based on other outcomes (HKT, renal recovery, composite HKT/renal recovery) did not reach statistical significance. Conclusions: The 18.8% of patients who achieved dual heart and kidney recovery and/or transplantation after being supported with LVAD and iHD experienced a significantly longer median survival. Only one patient experienced dual heart-kidney recovery. Larger contemporary multicenter cohort studies are warranted on this topic.Figure 1. Kaplan-Meier Survival Estimate (for the whole sample)Figure 2. Kaplan-Meier Survival Estimate According to Heart Transplant Status

The histone deacetylase inhibitor SAHA exerts a protective effect against myocardial ischemia/reperfusion injury by inhibiting sodium-calcium exchanger

Calcium overload performs a crucial function in the pathogenesis of myocardial ischemia-reperfusion (I/R) damage, which contributes to mitochondrial impairment and apoptosis of cardiomyocytes. Suberoylanilide hydroxamic acid (SAHA), a small molecule histone deacetylases inhibitor with modulatory capacity on Na+-Ca2+ exchanger (NCX), is proven to have protective potential towards cardiac remodeling and injury, but the mechanism remains unclear. Hence, Hence, our present research explored the modulation of NCX-Ca2+-CaMKII by SAHA in myocardial I/R damage. Our outcomes indicate that in vitro hypoxia and reoxygenation models of myocardial cells, SAHA treatment inhibited the increase in expression of NCX1, intracellular Ca2+ concentration, expression of CaMKII and self-phosphorylated CaMKII, and cell apoptosis. In addition, SAHA treatment improved myocardial cell mitochondrial swelling inhibited mitochondrial membrane potential diminution and the openness of the mitochondrial permeability transition pore, and protected against mitochondrial dysfunction following I/R injury. In vivo, SAHA treatment alleviated the decrease in FS% and EF%, the increase in the myocardial infarct area, and myocardial enzyme levels caused by I/R injury, while also reducing myocardial cell apoptosis, and inhibiting mitochondrial fission and mitochondrial membrane rupture. These results indicated that SAHA treatment alleviated myocardial cell apoptosis as well as mitochondrial dysfunction resulting from myocardial I/R impairment, and contributed to myocardial function recovery by inhibiting the NCX-Ca2+-CaMKII pathway. These findings offered additional theoretical support to explore the mechanism of SAHA as a therapeutic agent in cardiac I/R damage and develop new treatment strategies.

Changing Concepts in Treatment of ST-Segment Elevation Myocardial

ST-Segment Elevation Myocardial (STEMI) is a lifethreatening condition that requires emergent, complex, well-coordinated treatment. Although the primary goal of treatment is simple to describe, reperfusion as quickly as possible- the management process is complicated and is affected by multiple factors including location, patient and practitioners’ characteristics. Indeed, treatment of acute STEMI has progressed considerably over the past 100 years, from the early stages of bed rest and development of thrombolytics and myocardial reperfusion, to today’s current strategy with a variety of mechanical and pharmacologic modalities. But the debate continues regarding optimal antithrombotic/anticoagulant and interventional strategies employed. Given the scientific and technological advantages, treatment strategies can be catered to better suit the patient and their presentation. Fibrinolytic therapy did save the lives compared to placebo, but at best restored Thrombolysis in Myocardial Infarction (TIMI) 3 Flow in 55-70% cases with increased incidence of recurrent ischaemia and infarction and intracranial haemorrhage. From Primary Angioplasty in Myocardial Infarction (PAMI) to 23 RCTs of Thrombolysis in Myocardial Infarction (TIMI) Vs Lysis showed that there is significant reduction in death (7.0% Vs 9.3%), Re-infarction (2.5% Vs 6.8%), haemorrhagic stroke (0.1% Vs 1.0%) and total stroke (1.0%) in Percutaneous Coronary Intervention (PCI) group. STEMI success has plateaued because of suboptimal salvage of myocardium and high rates of non-culprit lesion related events and reperfusion injury. Promising approaches should be further explored like hypothermia, stem cell and super-saturated oxygen therapy and PiCSO to enhance myocardial recovery and reduce infarct size. Bangladesh J Medicine 2023; Vol. 34, No. 2(1) Supplement: 182