Viable Dysfunctional Myocardium Research Articles

PREDICTION OF MYOCARDIAL VIABILITY ON THE BASIS OF SERUMBNP AND HSTROPONIN I LEVELS IN PATIENTS WITH CORONARYARTERY DISEASEWITH LVSYSTOLIC DYSFUNCTION

Introduction: Coronary artery disease (CAD) is the leading cause of heart failure (HF). Only viable dysfunctional myocardium (hibernation) is potentially recoverable with restoration of adequate perfusion. Cardiac imaging modalities have emerged with the ability to differentiate between myocardial scar and viable myocardium and are now often used to direct therapy decisions including revascularization. Decrease in wall motion score (WMS) and improvement in LV ejection fraction (LVEF) during DSE is considered as a surrogate marker for viability of myocardium. It is largely unknown how cardiac specific biomarkers are released in relation the presence and extent of hibernation in patients with ischemic HF. The objectives of this study are to assess the relationship and interaction of the biomarkers BNP and hs TnI with hibernation in patients with chronic ischemic HF. Materials and methods: It is a single center observational study which is conducted in Department of Cardiology, S.M.S. Medical College, Jaipur. 70 eligible patients with suspected ischemic cardiomyopathy (ICMP) are prospectively recruited into an imaging study using DSE to determine viability of myocardium. The patients also had blood sampling at baseline to determine biomarkers. Results: Mean age (in yrs) of patients is 63.78 ± 10.69 years. No patient is in NYHA I. 25.7 % of patients are in NYHA II (18 patients); 36 patients (51.4%) are in NYHA III and 16 patients (22.8%) are in NYHA IV. On comparison of baseline characteristics among patients with different NYHA class, there is a progressive increase in level of cardiac biomarkers with increase in NYHA class. Both BNP and hs TnI levels are significantly elevated in patients with Improvement in EF >10% as compared with Improvement in EF <10% There is a continuous relationship between increasing degrees of hibernation and increasing BNP and hs Trop I levels. HsTrop I had predicted a positive 56.6% change in Improvement in LVEF. HsTrop I had predicted a positive 52.5% change in decrease in WMS. Conclusion: The current study support the novel concept that the extent of LV hibernation are determinant of serum BNP and hs Trop I elevation in patients with ischemic HF and hs Trop I levels in patients with ischemic HF relate to the degree of hibernation.

РАЗРАБОТКА И АПРОБАЦИЯ ПРИМЕНЕНИЯ ПЕРФУЗИОННОЙ ОФЭКТ В КОМБИНАЦИИ С ДАЛАРГИНОВОЙ ПРОБОЙ ДЛЯ ВЫЯВЛЕНИЯ ЖИЗНЕСПОСОБНОГО МИОКАРДА У ПОСТИНФАРКТНЫХ БОЛЬНЫХ

Purpose: To develop a functional stress-test with Dalargin used as a pharmacological stress agent and to study its diagnostic capabilities for quantifying the general and segmental systolic function of the left ventricle in patients with IHD using SPECT and echo methods.
 Material and methods: The study comprised 29 male patients with CHD-angina of 2-3 functional classes, studied on 15–25 days (on average 20 ± 2.8 days) after a large-focal myocardial infarction. A fractional step-wise injection of Dalargin was performed with step doses as 0.1 mg / kg (1 ml up to a total of 8 ml, with intervals of 90 seconds, for a total of 12 minutes), in a supine position. After each dose of Dalargin, blood pressure, heart rate, ECG were recorded, and an echocardiographic assessment of hemodynamic parameters and local contractility was carried out. At the peak of the effect of dalargin, 99mTc-Tetrofosmin was administered intravenously (370 – 540 MBq), followed by chest SPECT.
 Results: The optimal dose of dalargin for assessing the contractility of the LV was 0.3 mg/kg. From the data of myocardial perfusion SPECT, at dalargin test, the number of segments with normal regional blood supply increased statistically significantly from 56,0 % to 64,7 %, the number of hypoperfused segments decreased from 41.0% to 33.7% as compared to rest, and the number of non-perfused ones – from 3.0 % to 1.6 %. Spearman’s correlation coefficient between segmental contractility and local perfusion at the top dalargin inotropic effect was high and significant (R=0.67, p<0.01). The sensitivity and specificity of the pharmacological test with intravenous administration of dalargin for prediction of postoperative improvement of perfusion and contractility of the viable myocardium were: sensitivity 78.8 %, specificity 76.4 %, diagnostic accuracy 77.6 %.
 Conclusion. The use of the agonist of the μ - and δ-opioid receptors dalargin as a pharmacological stress-agent at perfusion SPECT and Stress Echocardiography to assess the contractile reserve of a dysfunctional viable myocardium is informative and appropriate. In patients with IHD who have suffered a myocardial infarction and are referred to myocardial revascularization, dalargin can be employed as an effective stress-agent for assessing the reserve of perfusion and contractility of dysfunctional left ventricular myocardium using perfusion SPECT and echocardiography.

Revascularization in Ischemic Heart Failure: A Review

Ischemic heart disease as a cause of heart failure is common in India, ranging from 48% to 71%. The pathoanatomic basis of LV dysfunction is not only due to infarcted myocardium, but also due to viable but dysfunctional myocardium (hibernating/stunned myocardium) and structural abnormalities (mitral regurgitation/ventricular septal defect aneurysm) consequent to obstructive coronary artery disease. Evaluation of dysfunctional but viable myocardium is a key determinant of recovery of LV function, and magnitude of recovery is proportional to the amount of dysfunctional viable myocardium which if more than 25% LV (4 segments out of 17 segments model) results in improvement in function and size (reverse remodeling). Most of the data regarding therapy come from observational, registry data showing better outcomes with coronary artery bypass graft than percutaneous coronary intervention and medical therapy. The need for more multicentric, randomized controlled trials regarding recovery of LV function by various therapies is more than ever now.

Echocardiography and CHA2DS2-VASc-HS score with adverse in-hospital outcomes in patients with non-st segment elevation myocardial infarction

Background After myocardial infarction, optimal clinical management depends critically on Echocardiography. Echocardiography is a versatile imaging modality for the management of patients with chest pain and assessment of left ventricular systolic function, diastolic function, and even myocardial and coronary perfusion which provides information regarding cardiac function and hemodynamics. Remodelling and heart failure, presence of inducible ischaemia, presence of dysfunctional viable myocardium, future risk of adverse events including risk of ventricular arrhythmias, need for anticoagulation, and other questions should be addressed. But it has some limitations. A clinical scoring is compared with echocardiography. Early detection of patients with non-ST segment elevation myocardial infarction (NSTEMI) who would suffer from adverse in-hospital outcomes is important for the therapeutic decision. Recently it was described that CHA2DS2-VASc-HS and CHA2DS2-VASc score is a predictor for severity and adverse in-hospital outcomes in patients with stable coronary artery disease (CAD) and acute coronary syndrome. The aim of our study was to assess the accuracy of the CHA2DS2-VASc-HS score predicting adverse in-hospital outcomes in NSTEMI patients. Methods 120 patients with NSTEMI were enrolled in this study. The CHA2DS2-VASc-HS score was calculated. The study subjects were divided into two groups. Patients’ with CHA2DS2-VASc-HS score > 4 were put into group I and score≤ 4 into group II. They were treated as per hospital treatment protocol and followed-up for adverse in-hospital outcomes (Heart failure, cardiogenic shock, recurrent ischemic pain, significant arrhythmia and death). Results It was observed that, patients with CHA2DS2-VASc-HS score > 4 had more adverse in-hospital outcomes than CHA2DS2-VASc-HS score ≤ 4 (20% vs. 3.3%, p = 0.01). Group I patients developed cardiogenic shock 10%, heart failure 4%, recurrent ischemia 11.7%, significant arrhythmia 1.7% and death 1.7% than group II patients (1.7%, 3.3%, 3.3%, 0% and 0% respectively). By risk measurement, CHA2DS2-VASc-HS score > 4 emerged as a risk factor for developing adverse in-hospital outcome (Relative risk = 6). Conclusion NSTEMI patients with high CHA2DS2-VASc-HS score have more adverse in-hospital outcomes. This score, which involves only clinical parameters, can be used as a predictor of outcomes in this group of patients.

Evaluation of the effectiveness and prognostic significance of the use of CMR in determining the viability of the myocardium

Aim: to evaluate the effectiveness of the cardiac magnetic resonance (CMR) method with delayed contrast for the diagnosis of viable dysfunctional myocardium. Materials and methods. А total of 148 patients participated in the analysis of the study. Inclusion criteria: myocardial infarction in past medical history; myocardial ischemia according to stress tests; occlusion or subtotal stenosis of one or more coronary arteries according to digital angiography (SYNTAX score 0.05). The incidence of non-fatal MI was 1.4 and 8.1% in groups I and II, respectively ( p < 0.05). Conclusion. CMR with delayed contrast is more effective and sensitive for diagnosis of myocardial viability and patient prognosis after endovascular intervention, compared with stress echocardiography with dobutamine.

Results of percutaneous coronary interventions in patients with dysfunctional myocardium.

Aim: to evaluate immediate and long-term results of endovascular treatment of patients with dysfunctional viable myocardium. Material and methods. 220 patients were included in the study and were divided into 2 groups. The main group (n=138) included patients with proven ischemia and the presence of viable myocardium in the post-MI zone, on account of which they performed endovascular intervention on the arteries that supply the viable myocardium. The control group (n=82) was formed retrospectively and included patients who were on optimal medical therapy, with invasive diagnostics and endovascular treatment not performed by such patients. The viability of the myocardium was determined by the methods ofMRI of the heart with delayed contrast and the method of stress echocardiography with dobutamine. Inclusion criteria: angina pectoris II-IV functional class (CCS); the presence of proven myocardial ischemia according to stress tests; occlusion or subtotal stenosis of one or more coronary arteries according to digital angiography (SYNTAX score &lt;32); presence of segments with disturbed local contractility of left ventricular myocardium; presence of a viable myocardium in the zone of the occluded / stenotic artery; circulatory failure of I-III functional class (NYHA); left ventricular ejection fraction (LVEF) less than 50%. Results. The magnetic resonance imaging (RMI) with delayed contrasting at the preoperative stage allows to reliably estimate the existing violations of local contractility in the zone of the hibernated myocardium, in comparison with the method of stress echocardiography with dobutamine. After 12 and 18 months of follow-up, there was a significant increase in the incidence of non-fatal MI in the control group. In all patients in the long-term period after PCI completion, a significant increase in the left ventricular ejection fraction and an improvement in the local contractility of the myocardium are noted. Among patients who underwent MRI of the heart, it was possible to detect a significant decrease in the mass fraction of ischemic myocardium in the post-MI zone. There was a strong positive correlation (r = 0.54, p&lt;0.05) between the duration of myocardial hibernation and the timing of restoration of its function after PCI. Conclusion. PCI performance in patients with dysfunctional viable myocardium is highly effective, compared with patients receiving only medication. The method of MRI of the heart with delayed contrast allows judging more objectively the dynamics Оригинальные исследования of the restoration of the function of the hibernated viable myocardium and remodeling of the heart after the revascularization, in comparison with stress echocardiography with dobutamine.

Impact of Myocardial Viability Assessed by Delayed Enhancement Cardiovascular Magnetic Resonance on Clinical Outcomes in Real World Practice

Background: Delayed enhancement cardiovascular magnetic resonance imaging (DeCMRI) has become the preferred method for viability assessment. It is well established that viable dysfunctional myocardium has the potential for functional recovery after revascularization.

Past, present, and future of acute heart failure clinical trials-a high-risk population in search of a strategy.

Past, present, and future of acute heart failure clinical trials-a high-risk population in search of a strategy.

Rationale and design of a randomized controlled trial of allogeneic mesenchymal stem cells in patients with nonischemic cardiomyopathy.

This article describes an ongoing study investigating the safety and efficacy of ischemia-tolerant mesenchymal stem cell (MSC) therapy in patients with nonischemic heart failure and dysfunctional viable myocardium without scarring. This study will follow principles of the previously described mechanistic translational-phase concept whereby the effect of the study agent on laboratory and imaging markers of cardiac structure and function will be tested in a small homogenous cohort with the goal to enhance the understanding of the effect of interventions on cardiac remodeling and performance. This single-blind, placebo-controlled, crossover, multicenter, randomized study will assess the safety, tolerability, and preliminary efficacy of a single intravenous (i.v.) dose of allogeneic ischemia-tolerant MSCs in individuals with heart failure of nonischemic cause, ejection fraction 40% or less, and dysfunctional viable myocardium who have been receiving guideline-directed medical therapy. Eligible patients will have no evidence of baseline replacement scarring on delayed-enhancement cardiac magnetic resonance (CMR). Approximately 20 patients will be randomized in a 1 : 1 ratio to receive an i.v. infusion of ischemia-tolerant MSCs or placebo. At 90 days, the two groups will undergo crossover and received the alternative treatment. The primary endpoint is safety, as evaluated through at least 1-year post-MSC infusion. Additional efficacy endpoints will include measures of cardiac structure and function, as evaluated by serial cine-CMR and transthoracic echocardiography at 90 and 180 days post-initial infusion. This pilot study will explore the safety and effects on cardiac structure and function of i.v. injection of ischemia-tolerant MSCs in a small homogenous cohort of nonischemic heart failure patients with reduced ejection fraction and absent replacement scarring on CMR. This study also represents a prospective mechanistic translational-phase study using baseline and serial CMR imaging in heart failure patients and serves as a potential model for design of future heart failure trials (ClinicalTrials.gov identifier: NCT02467387).

Revascularization of Chronic Hibernating Myocardium Stimulates Myocyte Proliferation and Partially Reverses Chronic Adaptations to Ischemia

BackgroundThe time course and extent of recovery after revascularization of viable dysfunctional myocardium are variable. Although fibrosis is a major determinant, myocyte structural and molecular remodeling may also play important roles. ObjectivesThis study sought to determine whether persistent myocyte loss and/or irreversibility of protein changes that develop in hibernating myocardium have an impact on functional recovery in the absence of infarction. MethodsSwine implanted with a chronic left anterior descending artery (LAD) stenosis to produce hibernating myocardium underwent percutaneous revascularization, with serial functional recovery evaluated for 1 month (n = 12). Myocardial tissue was evaluated to assess myocyte size, nuclear density, and proliferation indexes in comparison with those of normal animals and nonrevascularized controls. Proteomic analysis by 2-dimensional differential in-gel electrophoresis was used to determine the reversibility of molecular adaptations of hibernating myocytes. ResultsAt 3 months, physiological features of hibernating myocardium were confirmed, with depressed LAD wall thickening and no significant infarction. Revascularization normalized LAD flow reserve, with no immediate change in LAD wall thickening. Regional LAD wall thickening slowly improved but remained depressed 1 month post–percutaneous coronary intervention. Surprisingly, revascularization was associated with histological evidence of myocytes re-entering the growth phase of the cell cycle and increases in the number of c-Kit+ cells. Myocyte nuclear density returned to normal, whereas regional myocyte hypertrophy regressed. Proteomic analysis demonstrated heterogeneous effects of revascularization. Up-regulated stress and cytoskeletal proteins normalized, whereas reduced contractile and metabolic proteins persisted. ConclusionsDelayed recovery of hibernating myocardium in the absence of scar may reflect persistent reductions in the amounts of contractile and metabolic proteins. Although revascularization appeared to stimulate myocyte proliferation, the persistence of small immature myocytes may have contributed to delayed functional recovery.

Molecular and cellular basis of viable dysfunctional myocardium.

Heart failure is a leading cause of healthcare expenditures, hospitalization, and mortality in developed countries, and its burden is growing globally.1 With the aging of the population and increasing prevalence of chronic diseases, including hypertension, diabetes mellitus, and obesity, the current heart failure epidemic is guaranteed to significantly worsen in the near future. Thus, new disease-modifying treatments for heart failure are needed urgently and represent an area of intense investigation.2 Multiple studies in humans and animals have shown that the functionality of myocardial tissue of a failing heart can be restored. First, in ischemic heart failure because of severe coronary artery stenosis, revascularization therapy is known to improve heart function in a proportion of patients.3,4 Second, the mechanical unloading of the heart by left ventricular assist device (LVAD) is associated with improvements in cardiac function. In a recent report of 80 patients with heart failure who underwent implantation of a continuous-flow LVAD, the ejection fraction increased by >50% in about one third of the patients, with corresponding improvements in LV end-systolic and end-diastolic volumes and decreases in LV mass at 6 months after LVAD unloading.5 In addition, normalization of echocardiographic parameters has obviated completely the need for continuing LVAD support or cardiac transplantation in several patients.6,7 Importantly, the positive effects of mechanical unloading were noted in patients with both ischemic and nonischemic heart failure,5 suggesting that dysfunctional but potentially salvageable segments of myocardium exist in the failing heart regardless of pathogenesis. Third, in patients with broken heart syndrome (also known as Takotsubo cardiomyopathy), characterized by a rapid and severe loss of cardiac contractility secondary to emotional stress, myocardial function normalized spontaneously, again arguing for the reversibility of heart failure.8 In summary, although maladaptive changes observed in failing hearts were …

Myocardial oxygenation in hibernating myocardium: insights from blood oxygen level dependent imaging pre and post revascularization

Background The mechanisms underlying hibernating myocardium are controversial. Whether de-oxygenation occurs at rest and/or stress in severely dysfunctional viable (i.e. hibernating) myocardium is currently unknown. By utlising the paramagnetic properties of deoxy-haemoglobin, blood oxygen level dependent magnetic resonance imaging (BOLD-MRI) can detect oxygenation and myocardial ischemia. We applied BOLD imaging to examine the pathophysiological relationship between coronary stenosis, regional wall motion abnormalities, ventricular scar and myocardial oxygenation in hibernating myocardium. Methods BOLD imaging was acquired at rest and stress after 5 minutes of administration of adenosine (140 μg/kg/min) and assessed quantitatively (using a BOLD signal intensity index [stress/resting signal intensity] in 11 patients pre and median of 8 months (207, 299 days) post revascularisation. Late gadolinium (LGE) images were acquired using a T1 weighted segmented inversion recovery sequence and regional wall motion abnormalities (RWM) were scored pre and post revascularization using standard criteria. All segments were matched for BOLD, RWM and LGE analysis. Significant stenosis were classed as >50% by QCA. Results

Abstract 002: Blinded Head-to-Head Comparison of Intracoronary Allogeneic Cardiosphere-Derived Cells (icCDCs) Versus Allogeneic Mesenchymal Stem Cells (icMSCs) in Swine with Hibernating Myocardium

Background: Autologous icCDCs and icMSCs each improve myocardial function by stimulating endogenous myocyte proliferation. Since few myocytes arise directly from the injected cells, we evaluated the feasibility and comparative efficacy of allogeneic icCDCs vs. icMSCs. Methods: Studies were conducted in a blinded fashion. Immunosuppressed swine (cyclosporine 200 mg/day, N=26) with hibernating myocardium from a chronic LAD stenosis were randomized to receive vehicle, ~35 x 10 6 icMSCs, or ~35 x 10 6 icCDCs. Cells were infused into the 3 major coronary arteries at ~10 6 cells/min under continuous flow conditions. LAD function and pathologic indices of myocyte regeneration and proliferation were assessed 1 month later. Results: Baseline LAD wall thickening (%WT) was reduced in all animals (LAD 38 ± 2% vs. 83 ± 5% in remote, p&lt;0.01) but not different between treatment groups. One month later, LAD %WT remained depressed in vehicle-treated animals but increased to a similar extent following icCDCs and icMSCs (Table). Intracoronary cell therapy also produced large reciprocal increases in nuclear density and reductions in myocyte size with no differences between cell types. Indices of myocyte proliferation (Ki67 and phospho-Histone H3) remained elevated following icCDC treatment but had returned towards control in icMSC-treated animals. Conclusion: Our data demonstrate the feasibility of intracoronary allogeneic icCDC and icMSC infusion to treat viable dysfunctional myocardium without employing the “stop-flow” technique. Both cell types produce an equivalent increase in myocyte number and LAD function after 4-weeks but proliferative indices remain elevated after icCDCs.

The physiological significance of a coronary stenosis differentially affects contractility and mitochondrial function in viable chronically dysfunctional myocardium

The reversibility of viable dysfunctional myocardium after revascularization is variable and the reasons for this are unknown. Using 2D-DIGE, we tested the hypothesis that this could reflect the extent of molecular remodeling of myocardial tissue in the absence of infarction. Swine with a progressive left anterior descending (LAD) stenosis were studied 2 months (n = 18) or 3 months (n = 22) post-instrumentation. Coronary flow reserve (vasodilated/rest) was severely reduced at 2 months (LAD 2.6 ± 0.4 versus 5.1 ± 0.4 in normal, p < 0.05) and became critically impaired after 3 months (LAD 1.1 ± 0.2, p < 0.05 vs. 2 months). Despite progression in stenosis severity, reductions in wall thickening at 2 months (LAD 37 ± 4% vs. remote 86 ± 9%, p < 0.05) were unchanged at 3 months (LAD 32 ± 3%, p = ns). Contractile dysfunction was primarily related to reductions (LAD/normal) in contractile proteins which were not affected by stenosis severity (e.g., troponin T, 2 months 0.82 ± 0.03 vs. 0.74 ± 0.03 at 3 months, p-ns). In contrast, mitochondrial function and proteins were normal at 2 months but declined with progression to a critical stenosis (state 3 respiration at 3 months 145 ± 13 vs. 216 ± 5 ng-atoms O2 mg(-1) min(-1) at 2 months, p < 0.05). In a similar fashion, increases in stress (e.g., αB-crystalline 2.13 ± 0.2 vs. 1.17 ± 0.13 at 2 months, p < 0.05) and cytoskeletal proteins (e.g., desmin 1.63 ± 0.12 vs. 1.24 ± 0.10 at 2 months, p < 0.05) only developed with more advanced remodeling from a critical stenosis. We conclude that similar degrees of chronic contractile dysfunction can have diverse intrinsic molecular adaptations to ischemia. This spectrum of adaptations may underlie variability in the time course and extent of reversibility in viable chronically dysfunctional myocardium after revascularization.

Prognostic Value of Myocardial Viability by Delayed-Enhanced Magnetic Resonance in Patients With Coronary Artery Disease and Low Ejection Fraction: Impact of Revascularization Therapy

The purpose of this study was to evaluate the impact of myocardial viability assessment by delayed-enhanced cardiac magnetic resonance (DE-CMR) and of revascularization therapy on survival in patients with coronary artery disease (CAD) and low ejection fraction (EF). Prior studies have shown that DE-CMR predicts recovery of left ventricular (LV) dysfunction after revascularization. The authors prospectively evaluated survival of 144 consecutive patients (130 males, age 65 ± 11 years) with CAD and LV dysfunction (EF: 24 ± 7%) undergoing DE-CMR. Eighty-six patients underwent complete revascularization of dysfunctional myocardium (79 coronary artery bypass grafting, 7 percutaneous coronary intervention), whereas 58 patients remained under medical treatment. Over the 3-year median follow-up, 49 patients died. Three-year survival was significantly worse in medically treated patients with dysfunctional viable than with nonviable myocardium (48% vs. 77% survival, p = 0.02). By contrast, in revascularized patients, survival was similar whether myocardium was viable or not (88% and 71% survival, respectively, p = NS). Hazard of death of viable myocardium remaining under medical treatment versus complete revascularization was 4.56 (95% confidence interval [CI]: 1.93 to 10.8). Cox multivariate analysis indicated that interaction of revascularization and viability provided significant additional value (chi-square test = 13.1, p = 0.004) to baseline predictors of survival (New York Heart Association functional class, wall motion score, and peripheral artery disease). More importantly, in 43 pairs of propensity score-matched patients, hazard of death (hazard ratio: 2.5 [95% CI: 1.1 to 6.1], p = 0.02) remained significantly higher for medically treated patients rather than for those with fully revascularized viable myocardium. Without revascularization, presence of dysfunctional viable myocardium by DE-CMR is an independent predictor of mortality in patients with ischemic LV dysfunction. This observation may be useful for pre-operative selection of patients for revascularization.

Discrepancy between myocardial perfusion and fatty acid metabolism following acute myocardial infarction for evaluating the dysfunctional viable myocardium

ObjectiveFollowing acute myocardial infarction (AMI) the area of myocardial perfusion and metabolism mismatch is designated as dysfunctional viable myocardium. 123I-beta-methyl iodophenyl pentadecanoic acid (BMIPP) is clinically very useful for evaluating myocardial fatty acid metabolism, and 99mTc-Tetrofosmin (TF) is a widely used tracer for myocardial perfusion. This study was designed to evaluate the degree of discrepancy between BMIPP and TF at the subacute state of AMI. MethodsFifty-two patients (aged 59 ± 10 years; mean 46 years) with AMI were enrolled, and all of them underwent percutaneous coronary intervention (PCI). Patients were classified according to ST-T change and PCI timing. 123I-beta-methyl iodophenyl pentadecanoic acid and TF cardiac scintigraphy were performed on 7 ± 3.5 days of admission using a dual headed gamma camera. Perfusion and fatty acid metabolism defect were scored on a 17 segments model. ResultsThe mean BMIPP defect score on early and delayed images were 16.67 ± 10.19 and 16.25 ± 10.40, respectively. The mean TF defect score was 10 ± 7.69. Defect score of BMIPP was significantly higher than that of the TF (P < 0.0001; 95% CI 4.32–7.02), and there was a strong correlation between perfusion and metabolism defect score (r = 0.89, P < 0.00001). Forty-seven (90%) patients showed mismatched defect (BMIPP > TF), and 5 (10%) patients showed matched defect (BMIPP = TF). Mismatched defect score (MMDS) was significantly higher in patients with ST-segment elevation myocardial infarction (STEMI) than that of non-ST-segment elevation myocardial infarction (NSTEMI) (P < 0.041; 95% CI 0.11–5.19). ConclusionAt the subacute state of AMI, most of the patients showed perfusion-metabolism mismatch, which represents the dysfunctional viable myocardium, and patients with STEMI showed higher mismatch.

Abstract 8851: Intracoronary Infusion of Cardiosphere-Derived Cells (icCDCs) Improves Cardiac Function by Stimulating Myocyte Proliferation in Non-Infarcted Hibernating Myocardium with No Effect in Normal Myocardium

Background: icCDCs have been shown to improve function and reduce fibrotic area when regionally infused into infarcted myocardium. Their ability to improve flow and function in viable dysfunctional myocardium in the absence of scar is unclear. Methods: Swine (n=12) with collateral-dependent hibernating myocardium from a chronic LAD occlusion were studied 4-months after instrumentation in the closed-chest propofol sedated state. CDCs were isolated from myocardial biopsies at the time of initial instrumentation. We assessed regional flow, LAD wall thickening (%LADWT) and global EF before and 4 weeks after icCDCs (∼40x10 6 cells) into each of the 3 major coronary arteries. Autologous (n=3) as well as non-autologous CDCs with cyclosporine treatment (200mg/day; n=3) had similar effects and results were pooled and compared to untreated swine (n=6). Histological analysis was performed to assess the frequency of Ki-67 and phospho-Histone H3 (pHH3) positive myocytes along with myocyte nuclear density and myocyte diameter. Results: Infusion of icCDCs in normal animals (icCDCs; n=5 vs. untreated; n=6) did not affect regional (%LADWT 51±1% vs. 48±3%, p-ns) or global function (EF: 70±2% vs. 70±3%, p-ns). In contrast, in hibernating myocardium, %LADWT increased from 23±6 to 51±5 % (p&lt;0.01) and EF increased from 57±1 to 71±4 % (p&lt;0.01) after icCDCs. There was no change in LAD coronary flow reserve (adenosine vasodilated flow/ resting flow 1.88 ± 0.20 to 2.03 ± 0.31, p-ns). icCDCs increased the number of Ki-67 and pHH3 positive myocytes (Table). This was accompanied by a prominent increase in myocyte nuclear density with reduced myocyte size suggesting the formation of new myocytes. Conclusion: We conclude that icCDCs result in a robust improvement in function in hibernating myocardium. This is not secondary to increases in myocardial perfusion but is secondary to pronounced myocyte proliferation and regeneration with newly formed myocytes in diseased but not normal myocardium.

Abstract 9262: Prognostic Value of Myocardial Viability by Delayed Enhanced MR in Patients with Coronary Artery Disease and Low Ejection Fraction. Impact of Revascularization Therapy

Background. Prior works showed that delayed-enhanced cardiac magnetic resonance (DE-cMR) predicts recovery of left ventricular dysfunction (LVD) after revascularization in coronary artery disease (CAD). We sought to evaluate impact of myocardial viability assessment by DE-cMR and of revascularization therapy on survival of patients (pts) with low ejection fraction (EF). Methods and Results. We prospectively evaluated survival of 144 consecutive pts (130 males, 65±11 years) with CAD and LVD (EF 24±7%) undergoing DE-cMR. 86 pts underwent complete revascularization of dysfunctional myocardium (79 CABG, 7 PCI), while 58 pts remained under medical treatment. Pts were considered to have viable myocardium if &gt;4 dysfunctional segments had &lt;50% transmurality of DE. Over 3-years median follow-up 49 pts died. 3-year survival was significantly worse in pts with dysfunctional viable myocardium remaining under medical treatment (48%) than in medically treated pts with non-viable myocardium (77%, p=0.02 by log-rank test). By contrast, in revascularized pts, survival was similar whether myocardium was viable or not (88 and 71% survival respectively, p=NS). Hazard of death of medically treated viable myocardium was 4.56 [95% CI 1.93-10.8]. Cox multivariate analysis indicated that interaction of revascularization and viability provided significant additional value (X2=13.1, p=.004) to baseline predictors of survival (NYHA class, wall motion score and peripheral arterial disease). More importantly, in 43 pairs of propensity score matched pts for treatment selection, hazard of death (2.5 [95% CI 1.1-6.1, p=0.02]) remained significantly higher for medically treated rather than revascularized viable myocardium (Figure). Conclusions. Without revascularization, presence of viable myocardium by DE-cMR is an independent predictor of mortality in pts with ischemic LVD. This observation may be useful for preoperative selection of pts for revascularization.

Cardiac imaging after myocardial infarction

After myocardial infarction, optimal clinical management depends critically on cardiac imaging. Remodelling and heart failure, presence of inducible ischaemia, presence of dysfunctional viable myocardium, future risk of adverse events including risk of ventricular arrhythmias, need for anticoagulation, and other questions should be addressed by cardiac imaging. Strengths and weaknesses, recent developments, choice, and timing of the different non-invasive techniques are reviewed for this frequent clinical scenario.

123I-BMIPP and 99mTc-TF discordance on myocardial scintigraphy and it’s correlation with functional recovery following acute myocardial infarction: role of conventional echocardiography

(123)I-beta-methyl-iodophenyl pentadecanoic acid (BMIPP) and (99m)Tc-Tetrofosmin (TF) mismatch designated as stunned myocardium having both systolic and diastolic components. The degree of mismatch might reflect subsequent functional improvement, and this study was designed to unravel the impact of mismatched defect score (MMDS) on recovery of both systolic and diastolic function following acute myocardial infarction (AMI). Forty patients with recent AMI were recruited, and all of them underwent emergency percutaneous coronary intervention. Echocardiography and BMIPP and TF cardiac scintigraphy were performed on 7 +/- 3 days of admission. Follow up echocardiography was performed after 3 months. MMDS were compared with the systolic [ejection fraction (EF) and wall motion score index (WMSI)] and diastolic [peak velocity of early diastolic filling of mitral inflow/peak early diastolic velocity of the mitral annulus(E/E') and left atrial volume index(LAVI)] parameters. BMIPP defect score was significantly higher than the TF defect score and there was a strong positive correlation between them (r = 0.90, P < 0.00001). Thirty-two (80%) patients showed mismatched defect and rest 8(20%) showed matched defect. Of 32 patients 24(75%), 22(69%), 19(59%), and 20(62.5%) showed improved EF, WMSI, E/E' and LAVI respectively. Conversely out of 8 only 2(25%), 1(12.5%), and 2(25%) patients showed improvement of EF, WMSI and LAVI, respectively. E/E' was not improved in patients with matched defect. MMDS were significantly correlated with the improvement of EF (r = -0.46, P = 0.002), WMSI (r = 0.41, P = 0.007), E/E' (r = 0.56, P < 0.0002), and LAVI (r = 0.44, P = 0.004). Mismatched defect score could predict the approximate amount of viable dysfunctional myocardium, and the degree of mismatch showed a significant correlation with the improvement of both systolic and diastolic function.