Time course of infarct healing and left ventricular remodelling in patients with reperfused ST segment elevation myocardial infarction using comprehensive magnetic resonance imaging.
TL;DR: Infarct healing, with shrinkage of infarcted myocardium and wall thinning, occurs early post-MI as reflected by loss in LV mass and adjacent myocardial remodelling.
Abstract: Objective
To describe the time course of myocardial infarct (MI) healing and left ventricular (LV) remodelling and to assess factors predicting LV remodelling using cardiac MRI.
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TL;DR: In this early-stage study of patients with ICM, transendocardial injection of allogeneic and autologous MSCs without a placebo control were both associated with low rates of treatment-emergent SAEs, including immunologic reactions.
Abstract: Context Mesenchymal stem cells (MSCs) are under evaluation as a therapy for ischemic cardiomyopathy (ICM). Both autologous and allogeneic MSC therapies are possible; however, their safety and efficacy have not been compared. Objective To test whether allogeneic MSCs are as safe and effective as autologous MSCs in patients with left ventricular (LV) dysfunction due to ICM. Design, Setting, and Patients A phase 1/2 randomized comparison (POSEIDON study) in a US tertiary-care referral hospital of allogeneic and autologous MSCs in 30 patients with LV dysfunction due to ICM between April 2, 2010, and September 14, 2011, with 13-month follow-up. Intervention Twenty million, 100 million, or 200 million cells (5 patients in each cell type per dose level) were delivered by transendocardial stem cell injection into 10 LV sites. Main Outcome Measures Thirty-day postcatheterization incidence of predefined treatment-emergent serious adverse events (SAEs). Efficacy assessments included 6-minute walk test, exercise peak VO 2 , Minnesota Living with Heart Failure Questionnaire (MLHFQ), New York Heart Association class, LV volumes, ejection fraction (EF), early enhancement defect (EED; infarct size), and sphericity index. Results Within 30 days, 1 patient in each group (treatment-emergent SAE rate, 6.7%) was hospitalized for heart failure, less than the prespecified stopping event rate of 25%. The 1-year incidence of SAEs was 33.3% (n = 5) in the allogeneic group and 53.3% (n = 8) in the autologous group (P = .46). At 1 year, there were no ventricular arrhythmia SAEs observed among allogeneic recipients compared with 4 patients (26.7%) in the autologous group (P = .10). Relative to baseline, autologous but not allogeneic MSC therapy was associated with an improvement in the 6-minute walk test and the MLHFQ score, but neither improved exercise VO 2 max. Allogeneic and autologous MSCs reduced mean EED by −33.21% (95% CI, −43.61% to −22.81%; P Conclusions In this early-stage study of patients with ICM, transendocardial injection of allogeneic and autologous MSCs without a placebo control were both associated with low rates of treatment-emergent SAEs, including immunologic reactions. In aggregate, MSC injection favorably affected patient functional capacity, quality of life, and ventricular remodeling. Trial Registration clinicaltrials.gov Identifier: NCT01087996
1,049 citations
Cites background from "Time course of infarct healing and ..."
...Reverse remodeling was also evident by a reduction in the LV sphericity index (Figure 3).(21,22) Left ventricular volumes in individual groups revealed a statistically significant reduction in LV end-diastolic volumes only in the allogeneic group (Figure 3, eTable 2)....
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Journal Article•
TL;DR: In this article, the authors aimed to test whether pathological LVH, such as occurs in hypertrophic cardiomyopathy (HCM), hypertensive heart disease, or aortic stenosis, and physiological LVH in athletes, can be distinguished by means of left ventricular volume and geometric indices, derived from cardiovascular magnetic resonance imaging.
Abstract: Purpose. Determination of the underlying etiology of left ventricular hypertrophy (LVH) is a common, challenging, and critical clinical problem. The authors aimed to test whether pathological LVH, such as occurs in hypertrophic cardiomyopathy (HCM), hypertensive heart disease, or aortic stenosis, and physiological LVH in athletes, can be distinguished by means of left ventricular volume and geometric indices, derived from cardiovascular magnetic resonance imaging. Methods. A total of 120 subjects were studied on a 1.5 Tesla MR (Sonata, Siemens Medical Solutions, Erlangen, Germany) scanner, comprising healthy volunteers (18), competitive athletes (25), patients with HCM (35), aortic stenosis (24), and hypertensive heart disease (18). Left ventricular mass index, ejection fraction, end-diastolic, end-systolic and stroke volume index, diastolic wall thickness, wall thickness ratio and diastolic and systolic wall-to-volume ratios were determined. Results. Left ventricular (LV) mass indices were similar for al...
111 citations
TL;DR: New strategies have been developed to quantify myocardial viability using T1-mapping and equilibrium contrast enhanced MR techniques because existing delayed contrast enhancement MRI (DE-MRI) sequences are limited in detecting patchy microinfarct and diffuse fibrosis.
Abstract: Coronary artery disease is currently a worldwide epidemic with increasing impact on healthcare systems. Magnetic resonance imaging (MRI) sequences give complementary information on LV function, regional perfusion, angiogenesis, myocardial viability and orientations of myocytes. T2-weighted short-tau inversion recovery (T2-STIR), fat suppression and black blood sequences have been frequently used for detecting edematous area at risk (AAR) of infarction. T2 mapping, however, indicated that the edematous reaction in acute myocardial infarct (AMI) is not stable and warranted the use of edematous area in evaluating therapies. On the other hand, cine MRI demonstrated reproducible data on LV function in healthy volunteers and LV remodeling in patients. Noninvasive first pass perfusion, using exogenous tracer (gadolinium-based contrast media) and arterial spin labeling MRI, using endogenous tracer (water), are sensitive and useful techniques for evaluating myocardial perfusion and angiogenesis. Recently, new strategies have been developed to quantify myocardial viability using T1-mapping and equilibrium contrast enhanced MR techniques because existing delayed contrast enhancement MRI (DE-MRI) sequences are limited in detecting patchy microinfarct and diffuse fibrosis. These new techniques were successfully used for characterizing diffuse myocardial fibrosis associated with myocarditis, amyloidosis, sarcoidosis heart failure, aortic hypertrophic cardiomyopathy, congenital heart disease, restrictive cardiomyopathy, arrhythmogenic right ventricular dysplasia and hypertension). Diffusion MRI provides information regarding microscopic tissue structure, while diffusion tensor imaging (DTI) helps to characterize the myocardium and monitor the process of LV remodeling after AMI. Novel trends in hybrid imaging, such as cardiac positron emission tomography (PET)/MRI and optical imaging/MRI, are recently under intensive investigation. With the promise of higher spatial-temporal resolution and 3D coverage in the near future, cardiac MRI will be an indispensible tool in the diagnosis of cardiac diseases, coronary intervention and myocardial therapeutic delivery.
91 citations
Cites background from "Time course of infarct healing and ..."
...Additionally, DEMRI has the potential of measuring infarct resorption in animal models (57,58) and humans (59-61)....
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TL;DR: Luminal coronary artery diameter remained unaffected 3 months after epicardial IRE, purposely targeting the coronary arteries, and IRE can create deep lesions and is a safe modality for catheter ablation on or near coronary arteries.
Abstract: Background— Permanent coronary artery damage is a hazardous complication of epicardial radiofrequency ablation. Irreversible electroporation (IRE) is a promising nonthermal ablation modality able to create deep myocardial lesions. We investigated the effects of epicardial IRE on luminal coronary artery diameter and lesion depth. Methods and Results— In 5 pigs (60–75 kg), the pericardium was exposed using surgical subxiphoidal epicardial access. A custom deflectable octopolar 12-mm circular catheter with 2-mm ring electrodes was introduced in the pericardium via a steerable sheath. After coronary angiography (CAG), the proximal, mid, and distal left anterior descending, and circumflex coronary arteries were targeted with a single, cathodal 200 J application. CAG was repeated after IRE and after 3 months follow-up. Using quantitative CAG, the minimal luminal diameter at the lesion site was compared with the average of the diameters just proximal and distal to that lesion. Intimal hyperplasia and lesion size were measured histologically. CAG directly postablation demonstrated short-lasting luminal narrowing with normalization in the targeted area, suggestive of coronary spasm. After 3 months, all CAGs were identical to preablation CAGs: mean reference luminal diameter was 2.2±0.3 mm, mean luminal diameter at the lesion site was 2.1±0.3 mm ( P =0.35). Average intimal hyperplasia in all arteries was 2±4%. Median lesion depth was 6.4±2.6 mm. Conclusions— Luminal coronary artery diameter remained unaffected 3 months after epicardial IRE, purposely targeting the coronary arteries. IRE can create deep lesions and is a safe modality for catheter ablation on or near coronary arteries.
86 citations
Cites methods from "Time course of infarct healing and ..."
...Large lesions often showed tissue shrinkage as also seen after myocardial infarction.(14) When sufficient undamaged myocardium was present in the histological section, the estimated original epicardial contour was used to measure lesion depth....
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TL;DR: In an epicardial porcine model with blood around the application site, continuous circular lesions, deep enough for electric pulmonary vein isolation, were created with a single circular 200-J application.
Abstract: Background— Recently, we demonstrated the feasibility and safety of circular electroporation ablation in porcine pulmonary vein ostia, but the relationship between the magnitude of the application and lesion dimensions is still unknown.
Methods and Results— An in vivo porcine study was performed on left ventricular epicardium submerged under 10 mm of blood, using devices that mimic a 20-mm-diameter 7F circular ablation catheter. Model D contained 10 separate electrodes, whereas model M consisted of 1 circular electrode. Ablations were performed at 50, 100, and 200 J with model D and at 100 J with model M. Lesion dimensions were measured after 3-week survival. All applications resulted in smooth voltage waveforms demonstrating the absence of vapor globe formation, arcing, and a pressure wave. Applications up to 100 J with model D resulted in separate lesions under the electrodes. At 200 J, continuous deep circular lesions were created despite the use of separate electrodes. There was a significant relationship between applied current and median lesion depth, with a slope of 0.17 mm/A. At 100 J, there was no difference in lesion depth or width between models D and M. The electrodes and ablation site directly after ablation showed no signs of thermal damage.
Conclusions— In an epicardial porcine model with blood around the application site, continuous circular lesions, deep enough for electric pulmonary vein isolation, were created with a single circular 200-J application. Lesions were continuous despite the use of separate electrodes. Lesion depth increased with the magnitude of the application.
76 citations
Cites methods from "Time course of infarct healing and ..."
...Large lesions often showed tissue thinning, as is also common after myocardial infarction.(8) When sufficient undamaged myocardium was present in the histological section, the estimated original epicardial contour was used to measure lesion depth....
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References
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TL;DR: Valsartan is as effective as captopril in patients who are at high risk for cardiovascular events after myocardial infarction and the combination of the two on mortality in this population of patients.
Abstract: background Angiotensin-converting–enzyme (ACE) inhibitors such as captopril reduce mortality and cardiovascular morbidity among patients with myocardial infarction complicated by left ventricular systolic dysfunction, heart failure, or both. In a double-blind trial, we compared the effect of the angiotensin-receptor blocker valsartan, the ACE inhibitor captopril, and the combination of the two on mortality in this population of patients. methods Patients receiving conventional therapy were randomly assigned, 0.5 to 10 days after acute myocardial infarction, to additional therapy with valsartan (4909 patients), valsartan plus captopril (4885 patients), or captopril (4909 patients). The primary end point was death from any cause. results During a median follow-up of 24.7 months, 979 patients in the valsartan group died, as did 941 patients in the valsartan-and-captopril group and 958 patients in the captopril group (hazard ratio in the valsartan group as compared with the captopril group, 1.00; 97.5 percent confidence interval, 0.90 to 1.11; P=0.98; hazard ratio in the valsartanand-captopril group as compared with the captopril group, 0.98; 97.5 percent confidence interval, 0.89 to 1.09; P=0.73). The upper limit of the one-sided 97.5 percent confidence interval for the comparison of the valsartan group with the captopril group was within the prespecified margin for noninferiority with regard to mortality (P=0.004) and with regard to the composite end point of fatal and nonfatal cardiovascular events (P<0.001). The valsartan-and-captopril group had the most drug-related adverse events. With monotherapy, hypotension and renal dysfunction were more common in the valsartan group, and cough, rash, and taste disturbance were more common in the captopril group. conclusions Valsartan is as effective as captopril in patients who are at high risk for cardiovascular events after myocardial infarction. Combining valsartan with captopril increased the rate of adverse events without improving survival.
2,305 citations
"Time course of infarct healing and ..." refers background in this paper
...Adverse LV remodelling, defined as an increase in LV end-systolic volume following myocardial infarction, is associated with progression to heart failure and poor outcome, and is hence a widely used marker of disease severity [7]....
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TL;DR: CRT in patients with moderate-to-severe heart failure who were treated with optimal medical therapy is associated with reverse LV remodeling, improved systolic and diastolic function, and decreased MR.
Abstract: Background— Cardiac resynchronization therapy (CRT) has recently emerged as an effective treatment for patients with moderate to severe systolic heart failure and ventricular dyssynchrony. The purpose of the present study was to determine whether improvements in left ventricular (LV) size and function were associated with CRT. Methods and Results— Doppler echocardiograms were obtained at baseline and at 3 and 6 months after therapy in 323 patients enrolled in the Multicenter InSync Randomized Clinical Evaluation (MIRACLE) trial. Of these, 172 patients were randomized to CRT on and 151 patients to CRT off. Measurements were made of LV end-diastolic and end-systolic volumes, ejection fraction, LV mass, severity of mitral regurgitation (MR), peak transmitral velocities during early (E-wave) and late (A-wave) diastolic filling, and the myocardial performance index. At 6 months, CRT was associated with reduced end-diastolic and end-systolic volumes (both P<0.001), reduced LV mass (P<0.01), increased ejection f...
1,128 citations
TL;DR: This study demonstrates the linkage between attenuation of left ventricular enlargement by captopril after infarction and improved clinical outcome and two-dimensional echocardiography provides important and independent prognostic information in patients afterinfarction.
Abstract: BACKGROUNDLeft ventricular enlargement after myocardial infarction increases the likelihood of an adverse outcome. In an echocardiographic substudy of the Survival and Ventricular Enlargement (SAVE) Trial, we assessed whether captopril would attenuate progressive left ventricular enlargement in patients with left ventricular dysfunction after acute myocardial infarction and, if so, whether this would be associated with improved clinical outcome.METHODS AND RESULTSTwo-dimensional transthoracic echocardiograms were obtained in 512 patients at a mean of 11.1 +/- 3.2 days after infarction and were repeated at 1 year in 420 survivors. Left ventricular size was assessed as left ventricular cavity areas at end diastole and end systole and left ventricular function as percent change in cavity area from end diastole to end systole. Patients were randomly assigned to placebo or captopril, and the incidence of adverse cardiovascular events consisting of cardiovascular death, heart failure requiring either hospitaliz...
819 citations
"Time course of infarct healing and ..." refers background in this paper
...The use of cardiac MRI appears particularly appealing both in clinical trials and to determine the effect of interventions for the individual patient [2]....
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TL;DR: Almost 26% of patients may develop limited leftventricular dilatation within 4 weeks after first infarction, which helps to restore cardiac index and stroke index at rest and to preserve exercise performance and therefore remains compensatory.
Abstract: BACKGROUNDLeft ventricular enlargement and the development of chronic heart failure are potent predictors of survival in patients after myocardial infarction. Prospective studies relating progressive ventricular enlargement in individual patients to global and regional cardiac dysfunction and the onset of late chronic heart failure are not available. It was the aim of this study to define the relation between left ventricular dilatation and global and regional cardiac dysfunction and to identify early predictors of enlargement and chronic heart failure in patients after myocardial infarction.METHODS AND RESULTSLeft ventricular volumes, regional area shrinkage fraction in 18 predefined sectors (gated single photon emission computed tomography), global ejection fraction, and hemodynamics at rest and during exercise (supine bicycle, 50 W, 4 minutes, Swan-Ganz catheter) were assessed prospectively 4 days, 4 weeks, 6 months, and 1.5 and 3 years after first myocardial infarction. Seventy patients were assigned ...
683 citations
TL;DR: MRI is a highly sensitive and reliable tool to detect morphologic and functional sequelae of AMI providing baseline MRI parameters with relevant predictive power for LV adverse remodelling and occurrence of MACE.
Abstract: Aims Because of its high spatial resolution and tissue contrast, magnetic resonance imaging (MRI) was used to assess cardiac structure and function in a large population of patients with acute myocardial infarction (AMI).
Methods and results One hundred and ten patients were studied by MRI 6.1±2.2 days after AMI. Infarct size (IS), persistent microvascular obstruction (PMO), left and right ventricular (LV/RV) volumes, and functions were measured. The same MRI measurements were repeated in 89 patients after a mean follow-up period of 225±92 days. IS was 11.9±7.3% of total LV muscle mass. PMO was detected in 51/110 (46.4%) patients and comprised 15.6±8.5% of IS and 2.8±2.3% of LV muscle mass. Papillary muscle infarct was seen in 26%, RV infarction in 16%, pericarditis in 40%, and pericardial effusion in 66% of the patients. During follow-up, there were 16 major adverse cardiac events (MACE) including seven deaths. IS, PMO, and amount of transmural infarction were predictive for LV adverse remodelling defined as >20% increase in LV end-diastolic volume. Multivariable analysis revealed LV end-diastolic volume, LV ejection fraction, and PMO as significant predictors for the occurrence of MACE.
Conclusion MRI is a highly sensitive and reliable tool to detect morphologic and functional sequelae of AMI providing baseline MRI parameters with relevant predictive power for LV adverse remodelling and occurrence of MACE.
482 citations