Determination of viable myocardium through delayed enhancement cardiac magnetic resonance imaging combined with 18F-FDG PET myocardial perfusion/metabolic imaging before CABG.

PURPOSE: Study aims to investigate the consistency of delayed enhancement cardiac magnetic resonance imaging (DE-CMR) and 18F-FDG PET myocardial imaging in evaluating myocardial viability before CABG. METHODS: The study analyzed data from 100 patients who were examined with DE-CMR, PET imaging, and echocardiography before and after CABG. All subjects were followed up for 6-12 month post- CABG. RESULTS: DE-CMR and PET imaging have high consistency (90.1%; Kappa value = 0.71, p < 0.01) in determining myocardial viability. The degree of delayed enhancement was negatively correlated with the improvement in myocardial contractile function in this segment after revascularization (P < 0.001). The ratio of scarred myocardial segments and total DE score was significantly lower in the improvement group than non-improvement group. Multivariate regression identified that hibernating myocardium (OR = 1.229, 95%CI: 1.053-1.433, p = 0.009) was influencing factor of LVEF improvement after CABG. CONCLUSION: Both imaging techniques are consistent in evaluating myocardial viability. Detecting the number of hibernating myocardium by PET is also important to predict the left heart function improvement after CABG.

Neurogenic myocardial dysfunction post craniopharyngioma resection: A diagnostic dilemma.

Endoscopic transsphenoidal resection of craniopharyngioma is a commonly used technique. Cerebral vasospasm may occur in nearly 10% of cases leading to adverse neurological outcomes. Cardiopulmonary dysfunction may be seen in patients with severe vasospasm. The literature describing the occurrence of neurogenic stunned myocardium following craniopharyngioma resection in pediatric patients is very sparse. Here, we describe such a case managed with a combination of milrinone (to relieve vasospasm and improve cardiac pump function), noradrenaline (to obtain target blood pressure), and vasopressin (to control urine output). This case report proposes the treatment plan of neurogenic stunned myocardium following vasospasm in pediatric patients.

From Neurocardiology to Stroke-Heart Syndrome.

The Stroke-Heart syndrome is a major chapter in neurocardiology. Both brain-heart and stroke-heart correlations are based on neurophysiological studies that define and describe the relation between the central autonomic system and cardiac function and it will be presented in this narrative review. The Stroke-Heart syndrome groups the entire spectrum of cardiac changes - clinical, ECG, echocardiographic, biological, morphological - that occur in the first 30 days from the onset of stroke, especially in the first days. Their presence significantly marks the evolution and prognosis of stroke. The damage resulted from hypothalamus-pituitary-adrenal axis activation and high catecholamine release (adrenergic storm) targets mainly the myocyte and the microcirculation.The Takotsubo syndrome and Stunned myocardium are distinct forms of neurogenic myocardial ischemia - with changes in ECG, parietal motility, and biological markers - usually reversible although evolution towards cardiac dysfunction is also possible. The concept of Stroke-Heart syndrome and the brain-heart correlation brought new scientific information regarding stress cardiomyopathy or neurogenic myocardial injury.

Stem cell-derived exosome patch with coronary artery bypass graft restores cardiac function in chronically ischemic porcine myocardium.

OBJECTIVE: This study aimed to investigate whether or not the application of a stem cell-derived exosome-laden collagen patch (EXP) during coronary artery bypass grafting (CABG) can recover cardiac function by modulating mitochondrial bioenergetics and myocardial inflammation in hibernating myocardium (HIB), which is defined as myocardium with reduced blood flow and function that retains viability and variable contractile reserve. METHODS: In vitro methods involved exposing H9C2 cardiomyocytes to hypoxia followed by normoxic coculture with porcine mesenchymal stem cells. Mitochondrial respiration was measured using Seahorse assay. GW4869, an exosomal release antagonist, was used to determine the effect of mesenchymal stem cells-derived exosomal signaling on cardiomyocyte recovery. Total exosomal RNA was isolated and differential micro RNA expression determined by sequencing. In vivo studies comprised 48 Yorkshire-Landrace juvenile swine (6 normal controls, 17 HIB, 19 CABG, and 6 CABG + EXP), which were compared for physiologic and metabolic changes. HIB was created by placing a constrictor on the proximal left anterior descending artery, causing significant stenosis but preserved viability by 12 weeks. CABG was performed with or without mesenchymal stem cells-derived EXP application and animals recovered for 4 weeks. Before terminal procedure, cardiac magnetic resonance imaging at rest, and with low-dose dobutamine, assessed diastolic relaxation, systolic function, graft patency, and myocardial viability. Tissue studies of inflammation, fibrosis, and mitochondrial morphology were performed posttermination. RESULTS: In vitro data demonstrated improved cardiomyocyte mitochondrial respiration upon coculture with MSCs that was blunted when adding the exosomal antagonist GW4869. RNA sequencing identified 8 differentially expressed micro RNAs in normoxia vs hypoxia-induced exosomes that may modulate the expression of key mitochondrial (peroxisome proliferator-activator receptor gamma coactivator 1-alpha and adenosine triphosphate synthase) and inflammatory mediators (nuclear factor kappa-light-chain enhancer of activated B cells, interferon gamma, and interleukin 1ß). In vivo animal magnetic resonance imaging studies demonstrated regional systolic function and diastolic relaxation to be improved with CABG + EXP compared with HIB (P = .02 and P = .02, respectively). Histologic analysis showed increased interstitial fibrosis and inflammation in HIB compared with CABG + EXP. Electron microscopy demonstrated increased mitochondrial area, perimeter, and aspect ratio in CABG + EXP compared with HIB or CABG alone (P < .0001). CONCLUSIONS: Exosomes recovered cardiomyocyte mitochondrial respiration and reduced myocardial inflammation through paracrine signaling, resulting in improved cardiac function.

Hematomyelia Presenting with Neurogenic Stunned Myocardium.

Various neurological disorders and emotional stress may cause left ventricular dysfunction, known as a neurogenic stunned myocardium. A previously healthy 71-year-old woman collapsed immediately after experiencing left arm numbness and pain. Thereafter, the patient complained of anterior chest pain and became comatose. An electrocardiogram showed ST-segment elevation of I, aVL, and V2-3 and depression of II, III, and aVF. Echocardiography revealed anteroseptal hypokinesis of the left ventricle. Emergency coronary angiography revealed no significant stenosis in the coronary arteries; however, left ventriculography revealed obvious anteroseptal hypokinesis. When the patient regained consciousness the following day, tetraplegia was observed. Spinal computed tomography and magnetic resonance imaging revealed an intramedullary spinal cord hemorrhage from the medulla to the conus. The cardiac function recovered, but the patient remained tetraplegic with poor spontaneous respiration. Although its incidence is extremely rare, hematomyelia should be recognized as a potential cause of neurogenic stunned myocardium.

Cardioprotective Effect of Acute Intradialytic Exercise: A Comprehensive Speckle-Tracking Echocardiography Analysis.

SIGNIFICANCE STATEMENT: Hemodialysis (HD) can lead to acute left ventricular (LV) myocardial wall motion abnormalities (myocardial stunning) due to segmental hypoperfusion. Exercise during dialysis is associated with favorable effects on central hemodynamics and BP stability, factors considered in the etiology of HD-induced myocardial stunning. In a speckle-tracking echocardiography analysis, the authors explored effects of acute intradialytic exercise (IDE) on LV regional myocardial function in 60 patients undergoing HD. They found beneficial effects of IDE on LV longitudinal and circumferential function and on torsional mechanics, not accounted for by cardiac loading conditions or central hemodynamics. These findings support the implementation of IDE in people with ESKD, given that LV transient dysfunction imposed by repetitive HD may contribute to heart failure and increased risk of cardiac events in such patients. BACKGROUND: Hemodialysis (HD) induces left ventricular (LV) transient myocardial dysfunction. A complex interplay between linear deformations and torsional mechanics underlies LV myocardial performance. Although intradialytic exercise (IDE) induces favorable effects on central hemodynamics, its effect on myocardial mechanics has never been comprehensively documented. METHODS: To evaluate the effects of IDE on LV myocardial mechanics, assessed by speckle-tracking echocardiography, we conducted a prospective, open-label, two-center randomized crossover trial. We enrolled 60 individuals with ESKD receiving HD, who were assigned to participate in two sessions performed in a randomized order: standard HD and HD incorporating 30 minutes of aerobic exercise (HDEX). We measured global longitudinal strain (GLS) at baseline (T0), 90 minutes after HD onset (T1), and 30 minutes before ending HD (T2). At T0 and T2, we also measured circumferential strain and twist, calculated as the net difference between apical and basal rotations. Central hemodynamic data (BP, cardiac output) also were collected. RESULTS: The decline in GLS observed during the HD procedure was attenuated in the HDEX sessions (estimated difference, -1.16%; 95% confidence interval [95% CI], -0.31 to -2.02; P = 0.008). Compared with HD, HDEX also demonstrated greater improvements from T0 to T2 in twist, an important component of LV myocardial function (estimated difference, 2.48°; 95% CI, 0.30 to 4.65; P = 0.02). Differences in changes from T0 to T2 for cardiac loading and intradialytic hemodynamics did not account for the beneficial effects of IDE on LV myocardial mechanics kinetics. CONCLUSIONS: IDE applied acutely during HD improves regional myocardial mechanics and might warrant consideration in the therapeutic approach for patients on HD.

Cardiac patterns for differentiation of neurogenic stunned myocardium in aneurysmal subarachnoid hemorrhage versus acute ischemic stroke.

AIMS: Neurogenic stunned myocardium (NSM) has heterogeneous presentations for acute ischemic stroke (AIS) and aneurysmal subarachnoid hemorrhage (SAH). We sought to better define NSM and differences between AIS and SAH by evaluating individual left ventricular (LV) functional patterns by speckle tracking echocardiography (STE). METHODS: We evaluated consecutive patients with SAH and AIS. Via STE, LV longitudinal strain (LS) values of basal, mid, and apical segments were averaged and compared. Different multivariable logistic regression models were created by defining stroke subtype (SAH or AIS) and functional outcome as dependent variables. RESULTS: One hundred thirty-four patients with SAH and AIS were identified. Univariable analyses using the chi-squared test and independent samples t-test identified demographic variables and global and regional LS segments with significant differences. In multivariable logistic regression analysis, when comparing AIS to SAH, AIS was associated with older age (OR 1.07, 95% CI 1.02-1.13, p = 0.01), poor clinical condition on admission (OR 7.74, 95% CI 2.33-25.71, p < 0.001), decreased likelihood of elevated admission serum troponin (OR .09, 95% CI .02-.35, p < 0.001), and worse LS basal segments (OR 1.18, 95% CI 1.02-1.37, p = 0.03). CONCLUSION: In patients with neurogenic stunned myocardium, significantly impaired LV contraction by LS basal segments was found in patients with AIS but not with SAH. Individual LV segments in our combined SAH and AIS population were also not associated with clinical outcomes. Our findings suggest that strain echocardiography may identify subtle forms of NSM and help differentiate the NSM pathophysiology in SAH and AIS.

An Adjuvant Stem Cell Patch with Coronary Artery Bypass Graft Surgery Improves Diastolic Recovery in Porcine Hibernating Myocardium.

Diastolic dysfunction persists despite coronary artery bypass graft surgery (CABG) in patients with hibernating myocardium (HIB). We studied whether the adjunctive use of a mesenchymal stem cells (MSCs) patch during CABG improves diastolic function by reducing inflammation and fibrosis. HIB was induced in juvenile swine by placing a constrictor on the left anterior descending (LAD) artery, causing myocardial ischemia without infarction. At 12 weeks, CABG was performed using the left-internal-mammary-artery (LIMA)-to-LAD graft with or without placement of an epicardial vicryl patch embedded with MSCs, followed by four weeks of recovery. The animals underwent cardiac magnetic resonance imaging (MRI) prior to sacrifice, and tissue from septal and LAD regions were collected to assess for fibrosis and analyze mitochondrial and nuclear isolates. During low-dose dobutamine infusion, diastolic function was significantly reduced in HIB compared to the control, with significant improvement after CABG + MSC treatment. In HIB, we observed increased inflammation and fibrosis without transmural scarring, along with decreased peroxisome proliferator-activated receptor-gamma coactivator (PGC1α), which could be a possible mechanism underlying diastolic dysfunction. Improvement in PGC1α and diastolic function was noted with revascularization and MSCs, along with decreased inflammatory signaling and fibrosis. These findings suggest that adjuvant cell-based therapy during CABG may recover diastolic function by reducing oxidant stress-inflammatory signaling and myofibroblast presence in the myocardial tissue.

Ginsenoside Rb1 Improves Post-Cardiac Arrest Myocardial Stunning and Cerebral Outcomes by Regulating the Keap1/Nrf2 Pathway.

The prognosis of cardiac arrest (CA) is dismal despite the ongoing progress in cardiopulmonary resuscitation (CPR). ginsenoside Rb1 (Gn-Rb1) has been verified to be cardioprotective in cardiac remodeling and cardiac ischemia/reperfusion (I/R) injury, but its role is less known in CA. After 15 min of potassium chloride-induced CA, male C57BL/6 mice were resuscitated. Gn-Rb1 was blindly randomized to mice after 20 s of CPR. We assessed the cardiac systolic function before CA and 3 h after CPR. Mortality rates, neurological outcome, mitochondrial homeostasis, and the levels of oxidative stress were evaluated. We found that Gn-Rb1 improved the long-term survival during the post-resuscitation period but did not affect the ROSC rate. Further mechanistic investigations revealed that Gn-Rb1 ameliorated CA/CPR-induced mitochondrial destabilization and oxidative stress, partially via the activation of Keap1/Nrf2 axis. Gn-Rb1 improved the neurological outcome after resuscitation partially by balancing the oxidative stress and suppressing apoptosis. In sum, Gn-Rb1 protects against post-CA myocardial stunning and cerebral outcomes via the induction of the Nrf2 signaling pathway, which may offer a new insight into therapeutic strategies for CA.

Persistent diastolic dysfunction in chronically ischemic hearts following coronary artery bypass graft.

OBJECTIVE: A porcine model was used to study diastolic dysfunction in hibernating myocardium (HM) and recovery with coronary artery bypass surgery (CABG). METHODS: HM was induced in Yorkshire-Landrace juvenile swine (n = 30) by placing a c-constrictor on left anterior descending artery causing chronic myocardial ischemia without infarction. At 12 weeks, animals developed the HM phenotype and were either killed humanely (HIB group; n = 11) or revascularized with CABG and allowed 4 weeks of recovery (HIB+CABG group; n = 19). Control pigs were matched for weight, age, and sex to the HIB group. Before the animals were killed humanely, cardiac magnetic resonance imaging (MRI) was done at rest and during a low-dose dobutamine infusion. Tissue was obtained for histologic and proinflammatory biomarker analyses. RESULTS: Diastolic peak filling rate was lower in HIB compared with control (5.4 ± 0.7 vs 6.7 ± 1.4 respectively, P = .002), with near recovery with CABG (6.3 ± 0.8, P = .06). Cardiac MRI confirmed preserved global systolic function in all groups. Histology confirmed there was no transmural infarction but showed interstitial fibrosis in the endomysium in both the HIB and HIB+CABG groups compared with normal myocardium. Alpha-smooth muscle actin stain identified increased myofibroblasts in HM that were less apparent post-CABG. Cytokine and proteomic studies in HM showed decreased peroxisome proliferator-activator receptor gamma coactivator 1-alpha (PGC1-α) expression but increased expression of granulocyte-macrophage colony-stimulating factor and nuclear factor kappa-light-chain enhancer of activated B cells (NFκB). Following CABG, PGC1-α and NFκB expression returned to control whereas granulocyte-macrophage colony-stimulating factor, tumor necrosis factor-α, and interferon gamma remained increased. CONCLUSIONS: In porcine model of HM, increased NFκB expression, enhanced myofibroblasts, and collagen deposition along with decreased PGC1-α expression were observed, all of which tended toward normal with CABG. Estimates of impaired relaxation with MRI within HM during increased workload persisted despite CABG, suggesting a need for adjuvant therapies during revascularization.

ATP-Sensitive Potassium Channel Opener Diazoxide Reduces Myocardial Stunning in a Porcine Regional With Subsequent Global Ischemia Model.

Background ATP-sensitive potassium channels are inhibited by ATP and open during metabolic stress, providing endogenous myocardial protection. Pharmacologic opening of ATP potassium channels with diazoxide preserves myocardial function following prolonged global ischemia, making it an ideal candidate for use during cardiac surgery. We hypothesized that diazoxide would reduce myocardial stunning after regional ischemia with subsequent prolonged global ischemia, similar to the clinical situation of myocardial ischemia at the time of revascularization. Methods and Results Swine underwent left anterior descending occlusion (30 minutes), followed by 120 minutes global ischemia protected with hyperkalemic cardioplegia±diazoxide (N=6 each), every 20 minutes cardioplegia, then 60 minutes reperfusion. Cardiac output, time to wean from cardiopulmonary bypass, left ventricular (LV) function, caspase-3, and infarct size were compared. Six animals in the diazoxide group separated from bypass by 30 minutes, whereas only 4 animals in the cardioplegia group separated. Diazoxide was associated with shorter but not significant time to wean from bypass (17.5 versus 27.0 minutes; P=0.13), higher, but not significant, cardiac output during reperfusion (2.9 versus 1.5 L/min at 30 minutes; P=0.05), and significantly higher left ventricular ejection fraction at 30 minutes (42.5 versus 15.8%; P<0.01). Linear mixed regression modeling demonstrated greater left ventricular developed pressure (P<0.01) and maximum change in ventricular pressure during isovolumetric contraction (P<0.01) in the diazoxide group at 30 minutes of reperfusion. Conclusions Diazoxide reduces myocardial stunning and facilitates separation from cardiopulmonary bypass in a model that mimics the clinical setting of ongoing myocardial ischemia before revascularization. Diazoxide has the potential to reduce myocardial stunning in the clinical setting.

Cardioprotective effects of enteral vs. parenteral lactoferrin administration on myocardial ischemia-reperfusion injury in a rat model of stunned myocardium.

BACKGROUND: Lactoferrin, an iron-binding glycoprotein, is known to have protective effects against intestinal and cerebral ischemia-reperfusion (IR) injuries; however, its cardioprotective effects against the stunned myocardium are unknown. This study aimed to test the hypothesis that lactoferrin has cardioprotective effects against stunned myocardium. METHODS: Using isolated rat hearts (Langendorff system), we determined the effects of lactoferrin administered enterally and by direct cardiac perfusion. Rat hearts were perfused using the Langendorff system, and two experiments were performed. In experiment 1, the hearts were divided into the enteral lactoferrin (E-LF) 7.5 m, 15 m, 30 m, and 60 m groups, where lactoferrin (1000 mg/kg) was administered enterally 7.5, 15, 30, and 60 min, respectively, before perfusion; and a control group, where saline was administered 30 min before perfusion. In experiment 2, hearts were allocated to the perfusate lactoferrin (P-LF) 15 and 100 groups, where 15 mg/L and 100 mg/L lactoferrin were respectively added to the perfusate, and a control group. Each group was perfused for 20 min prior to 15 min of no-flow ischemia with pacing, followed by 20 min of reperfusion. The primary outcome was the maximum left ventricular derivative of pressure development (LV dP/dt max) 15 min after reperfusion. Myocardial phospho-protein kinase B (p-Akt) was assayed using western blotting. RESULTS: The LV dP/dt max 15 min after reperfusion in the E-LF 15 and 30 m groups was significantly higher than that in the control group. However, the effects disappeared in the E-LF 60 m group. In the second experiment, there were no significant differences in LV dP/dt max. Myocardial p-Akt was not significantly activated in any lactoferrin group. CONCLUSION: Cardioprotection was observed 15-30 min after enteral lactoferrin but not by direct cardiac perfusion with lactoferrin. Myocardial p-Akt was not associated with the cardioprotective effect. The cardioprotective effect may be induced by enteral lactoferrin-induced substances.

A Rare Case of Postoperative Extradural Hematoma in the Posterior Fossa Complicated by Both Stunned Myocardium and Neurogenic Pulmonary Edema.

Acute neurological insult can trigger a cascade of events in other organ systems such as the heart and lung. Neurogenic stunned myocardium (NSM) and Neurogenic pulmonary edema (NPE) are mostly reported after stroke, subarachnoid hemorrhage, or seizures whenever sympathetic storm and autonomic dysregulation occurs. We report here for the first time, a case of postoperative infratentorial extradural hematoma in a patient triggering NSM and NPE at the same time. The challenges involved in the management of such a patient are described in this case report. The patient was successfully managed and discharged home with no new neurological deficits.

Neurogenic stunned myocardium resulting from surgical brainstem handling during resection of paediatric recurrent medulloblastoma-a possible brain heart interaction.

BACKGROUND: Neurogenic stunned myocardium (NSM) is characterised by an acute onset cardiac dysfunction following an acute neurological insult which mimics acute coronary syndrome. CASE DETAILS: A 12-year-old male child was admitted to the neuro-intensive care unit (NICU) following midline suboccipital craniotomy and resection of recurrent medulloblastoma. Postoperatively, in NICU, he developed tachycardia and hypotension, which was unresponsive to fluid challenge requiring norepinephrine infusion. Intraoperatively, during tumour resection from the dorsal medulla, episodes of hypertension and bradycardia were observed. Intraoperative blood loss was adequately managed with a stable hemodynamic profile without postoperative anaemia. An electrocardiogram showed sinus tachycardia with T wave inversion, and blood investigation revealed elevated cardiac troponin T levels. Point of care ultrasound (POCUS) of heart and lung showed features of NSM. Infusion dobutamine was added to achieve a target mean arterial pressure of 65 mm Hg with concomitant furosemide infusion and fluid restriction. Daily POCUS assessment of cardiac contractility and volume status was done. The patient was weaned from vasoactive drugs and ventilator following improvement of cardiac function and was discharged from NICU after 17 days. CONCLUSION: NSM results from the excessive release of catecholamines following stimulation of trigger zones in the brain. To date, a handful of cases of pediatric NSM following primary brain tumour are reported where hydrocephalus resulted in trigger zone activation. In this presented case, direct brain stem stimulation during tumour resection might have triggered NSM. Irrespective of the cause, timely diagnosis and execution of supportive management in our patient resulted in a positive outcome.

Neurogenic stunned myocardium in acute ischemic stroke.

BACKGROUND AND PURPOSE: Neurogenic myocardial injury occurs as a result of dysregulation of autonomic nervous system. The aim of this study was to explore the frequency of elevated troponin and dynamic ST segment/T wave changes and their relation with left ventricular (LV) systolic functions in acute ischemic stroke patients. METHODS: One hundred and twenty-five patients (mean age: 65.1±15.2years, 76 male) presenting with acute ischemic stroke were consecutively included. 12-lead electrocardiogram was taken to assess dynamic ST segment/T wave changes, conventional transthoracic echocardiography to determine LV ejection fraction (LVEF). High-sensitive cardiac troponin I (hs-cTnI) level>0.04ng/mL was accepted as elevated. RESULTS: Twenty-seven patients (21.6%) had elevated hs-cTnI and 60 patients (48%) had dynamic ST segment/T wave changes. The stroke patients with elevated hs-cTnI had significantly higher NT-proBNP values (2302±3450pg/mL vs 799±2075pg/mL p<0.001) and higher frequency of ST segment/T wave changes (85.2% vs 37.8% p<0.001), and lower LVEF (52.2±13.6% vs 61.0±8.5% p=0.002) compared to patients with normal troponin levels. The patients with ST segment/T wave changes had significantly higher frequencies of hyper-lipidemia (31.7% vs 15.4% p=0.031) and coronary artery disease (CAD) (43.3% vs 13.8% p<0.001), hs-cTnI (0.19±0.55ng/mL vs 0.02±0.01ng/mL p<0.001) and NT-proBNP levels (1430±2564pg/mL vs 842±2425pg/mL p=0.016), and lower LVEF (56.1±11.7% vs 61.9±8.3% p=0.009). Linear regression analysis revealed presence of CAD, but not ST segment/T wave changes as an independent predictor of hs-cTnI (p=0.034). LVEF was independently associated with hs-cTnI (p=0.003) and presence of CAD (p=0.009) when adjusted by age, sex and presence of ST segment/T wave changes. CONCLUSION: Troponin elevation and ST segment/T wave changes occurring in patients suffering acute ischemic stroke, especially in those with CAD, may be a sign of neurogenic stunned myocardium.