Chronic Ischemic Left Ventricular Dysfunction Research Articles

Metabolomics of repetitive myocardial stunning in chronic multivessel coronary artery stenosis: Effect of non-selective and selective β1-receptor blockers.

Chronic coronary artery stenosis can lead to regional myocardial dysfunction in the absence of myocardial infarction by repetitive stunning, hibernation or both. The molecular mechanisms underlying repetitive stunning-associated myocardial dysfunction are not clear. We used non-targeted metabolomics to elucidate responses to chronically stunned myocardium in a canine model with and without β-adrenergic blockade treatment. After development of left ventricular systolic dysfunction induced by ameroid constrictors on the coronary arteries, animals were randomized to 3months of placebo, metoprolol or carvedilol. We compared these two β-blockers with their different β-adrenergic selectivities on myocardial function, perfusion and metabolic pathways involved in tissue undergoing chronic stunning. Control animals underwent sham surgery. Dysfunction in stunned myocardium was associated with reduced fatty acid oxidation and enhanced ketogenic amino acid metabolism, together with alterations in mitochondrial membrane phospholipid composition. These changes were consistent with impaired mitochondrial function and were linked to reduced nitric oxide and peroxisome proliferator-activated receptor signalling, resulting in a decline in adenosine monophosphate-activated protein kinase. Mitochondrial changes were ameliorated by carvedilol more than metoprolol, and improvement was linked to nitric oxide and possibly hydrogen sulphide signalling. In summary, repetitive myocardial stunning commonly seen in chronic multivessel coronary artery disease is associated with adverse metabolic remodelling linked to mitochondrial dysfunction and specific signalling pathways. These changes are reversed by β-blockers, with the non-selective inhibitor having a more favourable impact. This is the first investigation to demonstrate that β-blockade-associated improvement of ventricular function in chronic myocardial stunning is associated with restoration of mitochondrial function. KEY POINTS: The mechanisms responsible for the metabolic changes associated with repetitive myocardial stunning seen in chronic multivessel coronary artery disease have not been fully investigated. In a canine model of repetitive myocardial stunning, we showed that carvedilol, a non-selective β-receptor blocker, ameliorated adverse metabolic remodelling compared to metoprolol, a selective β1-receptor blocker, by improving nitric oxide synthase and adenosine monophosphate protein kinase function, enhancing calcium/calmodulin-dependent protein kinase, probably increasing hydrogen sulphide, and suppressing cyclic-adenosine monophosphate signalling. Mitochondrial fatty acid oxidation alterations were ameliorated by carvedilol to a larger extent than metoprolol; this improvement was linked to nitric oxide and possibly hydrogen sulphide signalling. Both β-blockers improved the cardiac energy imbalance by reducing metabolites in ketogenic amino acid and nucleotide metabolism. These results elucidated why metabolic remodelling with carvedilol is preferable to metoprolol when treating chronic ischaemic left ventricular systolic dysfunction caused by repetitive myocardial stunning.

Current Role of Myocardial Viability Imaging Using Positron Emission Tomography in Patients with Chronic Ischemic Heart Failure and Left Ventricular Dysfunction

Current Role of Myocardial Viability Imaging Using Positron Emission Tomography in Patients with Chronic Ischemic Heart Failure and Left Ventricular Dysfunction

Novel Approach for Assessing Postinfarct Myocardial Injury and Inflammation Using Hybrid Somatostatin Receptor Positron Emission Tomography/Magnetic Resonance Imaging.

Novel Approach for Assessing Postinfarct Myocardial Injury and Inflammation Using Hybrid Somatostatin Receptor Positron Emission Tomography/Magnetic Resonance Imaging.

Speckle-tracking echocardiography for predicting improvement of myocardial contractile function after revascularization: a meta-analysis of prospective trials

Some studies have indicated that the use of 2D-Speckle tracking echocardiography (2DSTE) aids in predicting recovery of myocardial contractile function after revascularization in patients with chronic ischemic left ventricular (LV) dysfunction or acute myocardial infarction (MI). The purpose of this meta-analysis was to evaluate the diagnostic accuracy of 2DSTE strain in the detection of myocardial viability at rest and during low-dose dobutamine (LDD) stress. A systematic review for all prospective trials using 2DSTE to assess myocardial viability until January 2019 was done. Using a standard approach of meta-analysis for diagnostic tests. Overall, nine studies including 525 patients with either chronic ischemic heart disease or acute MI fulfilled the inclusion criteria. Seven studies used longitudinal strain (LS) at rest, nine studies used circumferential strain (CS) at rest, four studies used LS during LDD stress, and four studies used CS during LDD stress. LS and CS during LDD stress showed equally high sensitivity (81.5% and 81.5% respectively) and specificity (81.3% and 81.4% respectively) for detecting reversible dysfunction. At rest, LS and CS showed equally lower sensitivity (67.1%, p < 0.0001 vs. LDD stress and 68.7%, p < 0.0001, vs. LDD stress, respectively) and specificity (64%, p < 0.0001 vs. LDD stress and 65.7%, p = 0.0008 vs. LDD stress, respectively) as compared with LDD stress. LS and CS by 2DSTE during LDD stress accurately identify reversible ischemic myocardial dysfunction in patients with chronic ischemic LV dysfunction or after MI. The use of LDD stress can be recommended over resting strain measures in this setting.

Myocardial Contrast Echocardiography – Use in Viability Assessment and Acute Myocardial Infarction

Myocardial contrast echocardiography (MCE) is now guideline-directed tool to assess myocardial perfusion both at rest and during stress. Its prognostic value has been established in the scenario of stable and unstable coronary artery disease and heart failure through assessment of myocardial ischemia, myocardial viability, coronary flow reserve, and microvascular dysfunction. We will discuss the pathophysiologic basis of MCE and its role in myocardial viability assessment both in the setting of chronic ischemic left ventricular dysfunction and acute myocardial infarction.

Comparison of Mesenchymal Stem Cell Efficacy in Ischemic Versus Nonischemic Dilated Cardiomyopathy

BackgroundIschemic cardiomyopathy (ICM) and dilated cardiomyopathy (DCM) differ in histopathology and prognosis. Although transendocardial delivery of mesenchymal stem cells is safe and provides cardiovascular benefits in both, a comparison of mesenchymal stem cell efficacy in ICM versus DCM has not been done.Methods and ResultsWe conducted a subanalysis of 3 single‐center, randomized, and blinded clinical trials: (1) TAC‐HFT (Transendocardial Autologous Mesenchymal Stem Cells and Mononuclear Bone Marrow Cells in Ischemic Heart Failure Trial); (2) POSEIDON (A Phase I/II, Randomized Pilot Study of the Comparative Safety and Efficacy of Transendocardial Injection of Autologous Mesenchymal Stem Cells Versus Allogeneic Mesenchymal Stem Cells in Patients With Chronic Ischemic Left Ventricular Dysfunction Secondary to Myocardial Infarction); and (3) POSEIDON‐DCM (Percutaneous Stem Cell Injection Delivery Effects on Neomyogenesis in Dilated Cardiomyopathy). Baseline and 1‐year cardiac structure and function and quality‐of‐life data were compared in a post hoc pooled analysis including ICM (n=46) and DCM (n=33) patients who received autologous or allogeneic mesenchymal stem cells. Ejection fraction improved in DCM by 7% (within‐group, P=0.002) compared to ICM (1.5%; within‐group, P=0.14; between‐group, P=0.003). Similarly, stroke volume increased in DCM by 10.59 mL (P=0.046) versus ICM (−0.2 mL; P=0.73; between‐group, P=0.02). End‐diastolic volume improved only in ICM (10.6 mL; P=0.04) and end‐systolic volume improved only in DCM (17.8 mL; P=0.049). The sphericity index decreased only in ICM (−0.04; P=0.0002). End‐diastolic mass increased in ICM (23.1 g; P<0.0001) versus DCM (−4.1 g; P=0.34; between‐group, P=0.007). The 6‐minute walk test improved in DCM (31.1 m; P=0.009) and ICM (36.3 m; P=0.006) with no between‐group difference (P=0.79). The New York Heart Association class improved in DCM (P=0.005) and ICM (P=0.02; between‐group P=0.20). The Minnesota Living with Heart Failure Questionnaire improved in DCM (−19.5; P=0.002) and ICM (−6.4; P=0.03; δ between‐group difference P=0.042) patients.ConclusionsMesenchymal stem cell therapy is beneficial in DCM and ICM patients, despite variable effects on cardiac phenotypic outcomes. Whereas cardiac function improved preferentially in DCM patients, ICM patients experienced reverse remodeling. Mesenchymal stem cell therapy enhanced quality of life and functional capacity in both etiologies.Clinical Trial Registration URL: http://www.clinicaltrials.gov. Unique identifiers: TAC‐HFT: NCT00768066, POSEIDON: NCT01087996, POSEIDON‐DCM: NCT01392625.

Chronic Enalapril and Carvedilol Therapy in Beagle Dogs with Induced Chronic Ischemic Left-Ventricular Dysfunction: Effects on Angiotensin Responsiveness

Chronic Enalapril and Carvedilol Therapy in Beagle Dogs with Induced Chronic Ischemic Left-Ventricular Dysfunction: Effects on Angiotensin Responsiveness

Непосредственные результаты чрескожных коронарных вмешательств у больных хронической ишемической болезнью сердца и дисфункцией левого желудочка.

Непосредственные результаты чрескожных коронарных вмешательств у больных хронической ишемической болезнью сердца и дисфункцией левого желудочка.

Clinical role of post-angioplasty hyperemic microvascular resistances in chronic ischemic left ventricular dysfunction.

To investigate the impact of hyperemic microvascular resistances (HMRs) on myocardial perfusion and contractility after percutaneous coronary intervention (PCI) in chronic ischemic left ventricular dysfunction (CILVD). The current retrospective study included 48 patients with CILVD of the left anterior descending territory undergoing HMRs assessment before and after PCI with a dual-sensor intracoronary pressure-flow wire. The severity of resting myocardial underperfusion and contractile dysfunction of the left anterior descending territory was scored as summed rest score (SRS-T) by single photon emission tomography, wall motion score index (WMSI-T) and left ventricular ejection fraction (LVEF) by transthoracic echocardiography before PCI and after 3 months. Patients were divided into two groups according to the mean post-PCI HMRs. Mean post-PCI HMRs were 2.05 ± 0.43 mmHg/cm/s; increased HMRs (i.e. >2 mmHg/cm/s) were found in 17 patients (35.4%, group B) (3.29 ± 0.77 mmHg/cm/s), whereas 31 patients (64.6%, group A) showed lower values (1.35 ± 0.34 mmHg/cm/s; P < 0.001). Pre-PCI HMRs, WMSI-T and SRS-T were similar among groups.After PCI, a significant improvement of LVEF, WMSI-T and SRS-T was observed only in group A (6.6 ± 7.4%, 0.44 ± 0.42 and 3.9 ± 2.9, respectively) compared with group B (1.3 ± 1.9%, 0.02 ± 0.07 and 1.1 ± 1.9; P = 0.011, P < 0.001 and P = 0.028, respectively).Post-PCI HMRs predicted the absence of improvement of LVEF and WMSI-T at a cutoff value of 1.95 mmHg/cm/s (area under the curve 0.69 and 0.73; P = 0.038 and 0.017, respectively), with a positive predictive value of 96 and 100%, respectively. Increased post-PCI HMRs may predict the lack of functional improvement of the revascularized myocardium in CILVD.

A model of acute congestion with progressive induction of pulmonary edema in sheep with chronic ischemic left-ventricular dysfunction: Preliminary results

A model of acute congestion with progressive induction of pulmonary edema in sheep with chronic ischemic left-ventricular dysfunction: Preliminary results

Prediction of Outcomes in Patients with Chronic Ischemic Cardiomyopathy by Layer-Specific Strain Echocardiography: A Proof of Concept

Cardiac magnetic resonance imaging (CMR) has been established as a powerful tool for predicting mortality. However, its application is limited by availability and various contraindications. The aim of this study was to evaluate the predictive value of layer-specific myocardial deformation analysis as assessed by strain echocardiography for cardiac events in patients with chronic ischemic left ventricular dysfunction in comparison with CMR. Three hundred ninety patients (mean age, 63±4years; 69% men; mean left ventricular ejection fraction [LVEF], 41±7%) with chronic ischemic cardiomyopathy were prospectively enrolled and underwent strain echocardiography and CMR within 3±1days. LVEF, wall motion score index, and circumferential strain (CS), longitudinal strain, and radial strain for total wall thickness and for three myocardial layers (endocardial, midmyocardial, and epicardial) were determined by echocardiography. The extent of total myocardial scar (TMS) was determined by CMR. Follow-up was obtained for a mean of 4.9±2.2years. Cardiac events were defined as readmission for worsening of heart failure, ventricular arrhythmias, or death of any cause. The incremental value of LVEF, strain parameters, and TMS to relevant clinical variables was determined in nested Cox models. There were 133 cardiac events (34%). Baseline clinical data associated with outcomes were age (hazard ratio [HR], 1.27; P=.04), diabetes mellitus (HR, 1.52; P=.001), and renal insufficiency (HR, 1.77; P=.001) by multivariate analysis. The addition of LVEF, global and endocardial strain parameters, and TMS increased the predictive power, but endocardial CS (HR, 1.52; P<.01) caused the greatest increment in model power (χ(2)=39.2, P<.001). Endocardial CS<-20% was found to be the optimal predictor of prognosis. Endocardial CS is a powerful predictor of cardiac events and appears to be a better parameter than LVEF, TMS by CMR, and other strain variables by echocardiography.

Prediction of long-term segmental and global functional recovery of hibernating myocardium after revascularisation based on low dose dobutamine and late gadolinium enhancement cardiovascular magnetic resonance.

BackgroundThis study sought to evaluate the relation between long-term segmental and global functional outcome after revascularisation in patients with chronic ischaemic left ventricular dysfunction (LVD) and baseline markers of viability: late gadolinium enhancement (LGE) transmurality and contractile reserve (CR).MethodsForty-two patients with chronic ischaemic LVD underwent low-dose dobutamine- (LDD) and late gadolinium enhancement (LGE) cardiovascular magnetic resonance (CMR) before surgical or percutaneous revascularisation. Regional and global left ventricular (LV) functions and LGE were repeatedly assessed 6 ± 1 and 35 ± 6 months after revascularisation. In total, 319 at baseline dysfunctional and successfully revascularised segments were available for statistical analysis.ResultsThe likelihood of long-term functional improvement was directly related to the presence of CR and inversely related to both the LGE and the degree of contractile dysfunction at baseline. The time course of functional improvement was protracted, with significantly more delay in segments with more extensive LGE (p = 0.005) and more severe contractile dysfunction at baseline (p = 0.002). The presence of CR was the predictor of earlier functional improvement (p < 0.0001). Using a definition of viable segment as a segment without any LGE or with any LGE and producing CR during LDD stimulation, ≥55% of viable segments from all dysfunctional and revascularised segments in a patient was the only independent predictor of significant improvement (≥5%) in the left ventricular ejection fraction (LVEF) after revascularisation, with a 72% sensitivity and an 80% specificity (AUC 0.76, p = 0.014). Reverse LV remodelling was observed in patients who had a significant amount of viable myocardium successfully revascularised.ConclusionsIn patients with chronic ischaemic LVD, improvement of dysfunctional but viable myocardium can be considerably delayed. Both the likelihood and the time course of functional improvement are related to the LGE, CR and the degree of contractile dysfunction at baseline. At 35 ± 6 months after revascularisation, patients with ≥55% of viable segments from all dysfunctional and revascularised segments significantly improve LVEF and experience reverse LV remodelling. A combination of LDD–CMR and LGE–CMR is a simple and powerful tool for identifying which patients with impaired LV function will benefit from revascularisation.

Long-acting beneficial effect of percutaneously intramyocardially delivered secretome of apoptotic peripheral blood cells on porcine chronic ischemic left ventricular dysfunction

The quantity of cells with paracrine effects for use in myocardial regeneration therapy is limited. This study investigated the effects of catheter-based endomyocardial delivery of secretome of 2.5 × 109 apoptotic peripheral blood mononuclear cells (APOSEC) on porcine chronic post-myocardial infarction (MI) left ventricular (LV) dysfunction and on gene expression. Closed-chest reperfused MI was induced in pigs by 90-min occlusion followed by reperfusion of the mid-LAD (day 0). At day 30, animals were randomized to receive porcine APOSEC (n = 8) or medium solution (control; n = 8) injected intramyocardially into the MI border zone using 3D NOGA guidance. At day 60, cardiac MRI with late enhancement and diagnostic NOGA (myocardial viability) were performed. Gene expression profiling of the infarct core, border zone, and normal myocardium was performed using microarray analysis and confirmed by quantitative real-time PCR. Injection of APOSEC significantly decreased infarct size (p < 0.05) and improved cardiac index and myocardial viability compared to controls. A trend towards higher LV ejection fraction was observed in APOSEC vs. controls (45.4 ± 5.9% vs. 37.4 ± 8.9%, p = 0.052). Transcriptome analysis revealed significant downregulation of caspase-1, tumor necrosis factor and other inflammatory genes in APOSEC-affected areas. rtPCR showed higher expression of myogenic factor Mefc2 (p < 0.05) and downregulated caspase genes (p < 0.05) in APOSEC-treated pigs. In conclusion, overexpression of MEF2c and repression of caspase was related to decreased infarct size and improved cardiac function in secretome-treated animals. Altered gene expression 1-month post-APOSEC treatment proved the long-acting effects of cell-free therapy with paracrine factors.

Transendocardial Mesenchymal Stem Cells and Mononuclear Bone Marrow Cells for Ischemic Cardiomyopathy

Whether culture-expanded mesenchymal stem cells or whole bone marrow mononuclear cells are safe and effective in chronic ischemic cardiomyopathy is controversial. To demonstrate the safety of transendocardial stem cell injection with autologous mesenchymal stem cells (MSCs) and bone marrow mononuclear cells (BMCs) in patients with ischemic cardiomyopathy. A phase 1 and 2 randomized, blinded, placebo-controlled study involving 65 patients with ischemic cardiomyopathy and left ventricular (LV) ejection fraction less than 50% (September 1, 2009-July 12, 2013). The study compared injection of MSCs (n=19) with placebo (n = 11) and BMCs (n = 19) with placebo (n = 10), with 1 year of follow-up. Injections in 10 LV sites with an infusion catheter. Treatment-emergent 30-day serious adverse event rate defined as a composite of death, myocardial infarction, stroke, hospitalization for worsening heart failure, perforation, tamponade, or sustained ventricular arrhythmias. No patient had a treatment-emergent serious adverse events at day 30. The 1-year incidence of serious adverse events was 31.6% (95% CI, 12.6% to 56.6%) for MSCs, 31.6% (95% CI, 12.6%-56.6%) for BMCs, and 38.1% (95% CI, 18.1%-61.6%) for placebo. Over 1 year, the Minnesota Living With Heart Failure score improved with MSCs (-6.3; 95% CI, -15.0 to 2.4; repeated measures of variance, P=.02) and with BMCs (-8.2; 95% CI, -17.4 to 0.97; P=.005) but not with placebo (0.4; 95% CI, -9.45 to 10.25; P=.38). The 6-minute walk distance increased with MSCs only (repeated measures model, P = .03). Infarct size as a percentage of LV mass was reduced by MSCs (-18.9%; 95% CI, -30.4 to -7.4; within-group, P = .004) but not by BMCs (-7.0%; 95% CI, -15.7% to 1.7%; within-group, P = .11) or placebo (-5.2%; 95% CI, -16.8% to 6.5%; within-group, P = .36). Regional myocardial function as peak Eulerian circumferential strain at the site of injection improved with MSCs (-4.9; 95% CI, -13.3 to 3.5; within-group repeated measures, P = .03) but not BMCs (-2.1; 95% CI, -5.5 to 1.3; P = .21) or placebo (-0.03; 95% CI, -1.9 to 1.9; P = .14). Left ventricular chamber volume and ejection fraction did not change. Transendocardial stem cell injection with MSCs or BMCs appeared to be safe for patients with chronic ischemic cardiomyopathy and LV dysfunction. Although the sample size and multiple comparisons preclude a definitive statement about safety and clinical effect, these results provide the basis for larger studies to provide definitive evidence about safety and to assess efficacy of this new therapeutic approach. clinicaltrials.gov Identifier: NCT00768066.

Myocardial Deformation Imaging by Two-Dimensional Speckle-Tracking Echocardiography for Prediction of Global and Segmental Functional Changes after Acute Myocardial Infarction: A Comparison with Late Gadolinium Enhancement Cardiac Magnetic Resonance

Myocardial deformation analysis by speckle-tracking echocardiography (STE) has been shown to accurately predict viability in patients with chronic ischemic left ventricular (LV) dysfunction. The aim of this study was to evaluate two-dimensional STE for the prediction of global and segmental LV functional changes after acute myocardial infarction (AMI) in comparison with late gadolinium enhancement (LGE) cardiac magnetic resonance (CMR). In 93 patients (mean age, 60 ± 11 years) with first AMIs (55 with ST-segment elevation myocardial infarctions and 38 with non-ST-segment elevation myocardial infarctions) treated with acute percutaneous coronary intervention, global peak longitudinal strain was determined to describe global function by STE, and peak systolic circumferential and longitudinal strain was determined for segmental function analysis. LGE CMR was performed to define the amounts of global and segmental myocardial scar. STE and LGE CMR were performed within 48 hours of AMI. At 6-month follow-up, transthoracic echocardiography was repeated to determine global und segmental LV recovery and adverse LV remodeling (increase in end-systolic volume > 15%). Accuracy to predict global functional improvement as well as LV remodeling at 6-month follow-up after AMI was similar for STE and LGE CMR (areas under the curve, 0.715 vs 0.729 [P = .8830] and 0.806 vs 0.824 [P = .7141], respectively). Peak systolic circumferential strain < -14.2% had sensitivity of 71.6% and specificity of 58.1% to predict segmental functional improvement. Compared with LGE CMR, the predictive accuracy of transmural STE for segmental functional improvement at 6-month follow-up was lower (area under the curve, 0.788 vs 0.668; P = .0001). Predictive accuracy for segmental functional improvement could be improved by analysis of endocardial circumferential strain (area under the curve, 0.700 vs 0.668 for transmural speckle-tracking echocardiographic analysis; P = .0023). Two-dimensional STE allows the prediction of global functional recovery as well as LV remodeling after AMI with accuracy comparable with that of LGE CMR. Accuracy to predict segmental functional recovery using transmural deformation analysis by two-dimensional STE is inferior compared with LGE CMR but can be improved by a layer-specific analysis of endocardial deformation.

CARVEDILOL POPULATION PHARMACOKINETIC ANALYSIS – APPLIED VALIDATION PROCEDURE

Carvedilol is a nonselective beta blocker/alpha-1 blocker, which is used for treatment of essential hypertension, chronic stable angina, unstable angina and ischemic left ventricular dysfunction. The aim of this study was to describe carvedilol population pharmacokinetic (PK) analysis as well as the validation of analytical procedure, which is an important step regarding this approach. In contemporary clinical practice, population PK analysis is often more important than standard PK approach in setting a mathematical model that describes the PK parameters. Also, it includes the variables that have particular importance in the drugs pharmacokinetics such as sex, body mass, dosage, pharmaceutical form, pathophysiological state, disease associated with the organism or the presence of a specific polymorphism in the isoenzyme important for biotransformation of the drug. One of the most frequently used approach in population PK analysis is the Nonlinear Modeling of Mixed Effects NONMEM modeling. Analytical methods used in the data collection period is of great importance for the implementation of a population PK analysis of carvedilol in order to obtain reliable data that can be useful in clinical practice. High performance liquid chromatography (HPLC) analysis of carvedilol is used to confirm the identity of a drug and provide quantitative results and also to monitor the efficacy of the therapy. Analytical procedures used in other studies could not be fully implemented in our research as it was necessary to perform certain modification and validation of the method with the aim of using the obtained results for the purpose of a population pharmacokinetic analysis. Validation process is a logical terminal phase of analytical procedure development that provides applicability of the procedure itself. The goal of validation is to ensure consistency of the method and accuracy of results or to confirm the selection of analytical method for a given sample and drug. This study confirmed the importance of using valid analytical procedure for the purpose of carvedilol population pharmacokinetic analysis. Identification of demographic, pathophysiological and other factors that may influence the population carvedilol PK parameters gives the physician the possibility of a more comprehensive overview of the patient and better optimization of the therapeutical regimen. Acta Medica Medianae 2013;52(3):18-24.

Prediction of global and segmental functional changes after acute myocardial infarction by 2D speckle-tracking echocardiography and cardiac magnetic resonance imaging

Purpose: Myocardial deformation analysis by 2-dimensional (2D) speckle-tracking echocardiography (STE) has been shown to accurately predict viability in patients with chronic ischemic LV dysfunction. This study evaluated STE for prediction of global and segmental left ventricular (LV) functional changes after acute myocardial infarction (AMI) in comparison with late gadolinium enhancement cardiac magnetic resonance (LGE). Methods: In 93 patients (60±11 years) with first AMI (55 with ST-segment elevation myocardial infarction (STEMI) and 38 with Non-ST-segment elevation myocardial infarction (NSTEMI)), all treated by acute percutaneous coronary intervention peak global longitudinal strain was determined to describe global function by STE and peak systolic circumferential strain was determined for segmental function analysis. LGE was performed to define the amount of global and segmental myocardial scar. STE and LGE were performed within 48 hours after AMI. At 6 months follow-up transthoracic echocardiography was repeated to determine global (increase of ejection fraction ≥5%) and segmental (improvement of wall motion score at least one grade) LV recovery as well as global LV remodeling (increase of end-systolic volume >15%). Results: Accuracy to predict global functional improvement and LV remodeling at 6 months follow-up after AMI was similar for STE vs. LGE (AUC=0.715 vs. AUC=0.729, p=0.8830 and AUC=0.806 vs. AUC=0.824; p=0.7141, respectively). In patients with STEMI accuracy of circumferential strain analysis by STE to predict segmental functional improvement was non-inferior compared to analysis of LGE (AUC=0.679 vs. AUC=0.755; p=0.0512), while in patients with NSTEMI accuracy of strain analysis by STE for prediction of segmental functional improvement was lower compared to LGE (AUC=0.666 vs. AUC=0.838; p=0.0004). Conclusions: In patients with AMI, accuracy to predict global functional recovery as well as LV remodeling by 2D STE is comparable to LGE. In patients with STEMI, myocardial deformation analysis by 2D STE allows prediction of segmental functional recovery with non-inferior accuracy compared to LGE, while accuracy to predict segmental functional improvement is less in patients with NSTEMI.

Outcome of Prolonged Ventricular Fibrillation and CPR in a Rat Model of Chronic Ischemic Left Ventricular Dysfunction

Patients with chronic left ventricular (LV) dysfunction are assumed to have a lower chance of successful CPR and lower likelihood of ultimate survival. However, these assumptions have rarely been documented. Therefore, we investigated the outcome of prolonged ventricular fibrillation (VF) and CPR in a rat model of chronic LV dysfunction. Sprague-Dawley rats were randomized to (1) chronic LV dysfunction: animals underwent left coronary artery ligation; and (2) sham control. Echocardiography was used to measure cardiac performance before surgery and 4 weeks after surgery. Four weeks after surgical intervention, 8 min of VF was induced and defibrillation was delivered after 8 min of CPR. LV dilation and low ejection fraction were observed 4 weeks after coronary ligation. With optimal chest compressions, coronary perfusion pressure values during CPR were well maintained and indistinguishable between groups. There were no differences in resuscitability and numbers of shock required for successful resuscitation between groups. Despite the significantly decreased cardiac index in LV dysfunction animals before induction of VF, no differences in cardiac index were observed between groups following resuscitation, which was associated with the insignificant difference in postresuscitation survival. In conclusion, the outcomes of CPR were not compromised by the preexisting chronic LV dysfunction.

MYOCARDIAL VIABILITY- ASSESSMENT AND CLINICAL RELEVANCE

The assessment of myocardial viability is an important indication for noninvasive imaging in patients with coronary artery disease and chronic ischemic left ventricular dysfunction. Left ventricular function is a major determinant of survival in coronary artery disease. The goal of myocardial viability assessment is to differentiate patients with potentially reversible from irreversible left ventricular dysfunction9. In patients with chronic coronary artery disease and left ventricular dysfunction, there exists an important subpopulation in which revascularization may significantly improve regional or global left ventricular function, as well as symptoms and hence therapeutic and prognostic benefits in selected patients. The underlying pathophysiology involves reversible myocardial dysfunction (hibernation or stunning) which may exist independently or may coexist within the same patient. Stunned myocardium refers to the state of persistent regional dysfunction after a transient period of ischemia followed by reperfusion, most commonly present in acute coronary syndromes. Hibernating myocardium refers to a condition of chronic sustained abnormal contraction due to chronic underperfusion in patients with coronary artery disease in whom revascularization causes recovery of function. These states of potentially reversible left ventricular dysfunction commonly have preserved cell membrane integrity and metabolic activity to maintain cellular functions in the absence of normal myocyte contractility secondary to resting ischemia. Stunned myocardium improves its function early post revascularization, whereas hibernating myocardium may need longer time to fully recover in function. Furthermore, exercise capacity improved in patients with viable myocardium, and long term prognosis appeared favorable if patients with viable myocardium underwent revascularization. Viable myocardium has unique characteristics and these form the basis for the different imaging modalities that are currently available for the assessment of myocardial viability. A number of diagnostic techniques have emerged for differentiating viable from non viable myocardium in dysfunctional regions. These include evaluation of regional perfusion, cell membrane integrity, and metabolism using nuclear techniques with various radionuclide tracers; contractile reserve using dobutamine echocardiography or magnetic resonance imaging. More conventional approaches of identifying scarred and necrotic myocardium including presence of occluded coronary artery, regional contractile dysfunction, Q waves on electrocardiogram have been shown to be less accurate. New modalities include use of metabolic tracers with single photon emission tomography (SPECT), precise quantitative metabolic evaluation with positron emission tomography (PET), assessment of microvascular integrity with contrast echocardiography and use of magnetic resonance imaging (MRI). Most of these techniques are reasonably accurate in predicting myocardial viability.

Revascularization in patients with chronic ischaemic myocardial dysfunction: insights from cardiovascular magnetic resonance imaging

In patients with chronic ischaemic left ventricular dysfunction, revascularization may lead to symptomatic and prognostic improvement. Cardiovascular magnetic resonance (CMR) imaging with its high spatial resolution provides the qualitative and quantitative, global and regional information on myocardial anatomy and function. In combination with a gadolinium-based contrast agent, CMR allows an accurate quantification of the myocardial scar and predicts the likelihood of functional recovery after revascularization. The aim of this review is to summarize our current understanding of the detection of myocardial viability using CMR, and why it may be the preferred technique in the assessment of patients with ischaemic cardiomyopathy.