Damien Mandry

Effect of Omega-3 Acid Ethyl Esters on Left Ventricular Remodeling After Acute Myocardial Infarction: The OMEGA-REMODEL Randomized Clinical Trial.

Background: Omega-3 fatty acids from fish oil have been associated with beneficial cardiovascular effects, but their role in modifying cardiac structures and tissue characteristics in patients who have had an acute myocardial infarction while receiving current guideline-based therapy remains unknown. Methods: In a multicenter, double-blind, placebo-controlled trial, participants presenting with an acute myocardial infarction were randomly assigned 1:1 to 6 months of high-dose omega-3 fatty acids (n=180) or placebo (n=178). Cardiac magnetic resonance imaging was used to assess cardiac structure and tissue characteristics at baseline and after study therapy. The primary study endpoint was change in left ventricular systolic volume index. Secondary endpoints included change in noninfarct myocardial fibrosis, left ventricular ejection fraction, and infarct size. Results: By intention-to-treat analysis, patients randomly assigned to omega-3 fatty acids experienced a significant reduction of left ventricular systolic volume index (–5.8%, P=0.017), and noninfarct myocardial fibrosis (–5.6%, P=0.026) in comparison with placebo. Per-protocol analysis revealed that those patients who achieved the highest quartile increase in red blood cell omega-3 index experienced a 13% reduction in left ventricular systolic volume index in comparison with the lowest quartile. In addition, patients in the omega-3 fatty acid arm underwent significant reductions in serum biomarkers of systemic and vascular inflammation and myocardial fibrosis. There were no adverse events associated with high-dose omega-3 fatty acid therapy. Conclusions: Treatment of patients with acute myocardial infarction with high-dose omega-3 fatty acids was associated with reduction of adverse left ventricular remodeling, noninfarct myocardial fibrosis, and serum biomarkers of systemic inflammation beyond current guideline-based standard of care. Clinical Trial Registration: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00729430.

Evaluation of Right Ventricular Remodeling Using Cardiac Magnetic Resonance Imaging in Co-Existent Chronic Obstructive Pulmonary Disease and Obstructive Sleep Apnea

Abstract Untreated chronic obstructive pulmonary disease (COPD) co-existing with obstructive sleep apnea (OSA), also known as overlap syndrome, has higher cardiovascular mortality than COPD alone but its underlying mechanism remains unclear. We hypothesize that the presence of overlap syndrome is associated with more extensive right ventricular (RV) remodeling compared to patients with COPD alone. Adult COPD patients (GOLD stage 2 or higher) with at least 10 pack-years of smoking history were included. Overnight laboratory-based polysomnography was performed to test for OSA. Subjects with an apnea-hypopnea index (AHI) >10/h were classified as having overlap syndrome (n = 7), else classified as having COPD-only (n = 11). A cardiac MRI was performed to assess right and left cardiac chambers sizes, ventricular masses, and cine function. RV mass index (RVMI) was markedly higher in the overlap group than the COPD-only group (19 ± 6 versus 11 ± 6; p = 0.02). Overlap syndrome subjects had a reduced RV remodeling index (defined as the ratio between RVMI and RV end-diastolic volume index) compared to the COPD-only group (0.27 ± 0.06 versus 0.18 ± 0.08; p = 0.02). In the overlap syndrome subjects, the extent of RV remodeling was associated with severity of oxygen desaturation (R2 = 0.65, p = 0.03). Our pilot results suggest that untreated overlap syndrome may cause more extensive RV remodeling than COPD alone.

Combined stress myocardial perfusion and late gadolinium enhancement imaging by cardiac magnetic resonance provides robust prognostic information to cardiac events

Background Accurate non-invasive risk stratification may management and impact survival of CAD patients. Stress perfusion CMR reliably assesses ventricular function, viability and myocardial ischemia in a single examination. While prognostic information may be derived from individual components of a comprehensive CMR exam, evidence that they provide complementary prognostic information is still limited. We sought to determine whether the presence of myocardial ischemia by stress perfusion CMR provides incremental prognostic information for major adverse cardiovascular events (MACE) beyond ventricular function, the presence of myocardial scar and traditional risk factors in a large cohort of patients referred for non-invasive assessment of CAD.

ST2 is reduced by high-dose omega-3 fatty acid treatment following acute MI and is correlated with reduction of the extracellular volume fraction of non-infarcted myocardium

ST2 is reduced by high-dose omega-3 fatty acid treatment following acute MI and is correlated with reduction of the extracellular volume fraction of non-infarcted myocardium Bobby Heydari, Shuaib Abdullah, James V Pottala, Ravi V Shah, Siddique A Abbasi, Damien Mandry, Heidi Lumish, Udo Hoffmann, Evan Appelbaum, Jiazuo Feng, Ron Blankstein, Michael Steigner, Joseph P McConnell, William Harris, Michael Jerosch-Herold, Raymond Y Kwong

Effect of Omega-3 Acid Ethyl Esters on Left Ventricular Remodeling After Acute Myocardial Infarction

Background: Omega-3 fatty acids from fish oil have been associated with beneficial cardiovascular effects, but their role in modifying cardiac structures and tissue characteristics in patients who have had an acute myocardial infarction while receiving current guideline-based therapy remains unknown. Methods: In a multicenter, double-blind, placebo-controlled trial, participants presenting with an acute myocardial infarction were randomly assigned 1:1 to 6 months of high-dose omega-3 fatty acids (n=180) or placebo (n=178). Cardiac magnetic resonance imaging was used to assess cardiac structure and tissue characteristics at baseline and after study therapy. The primary study endpoint was change in left ventricular systolic volume index. Secondary endpoints included change in noninfarct myocardial fibrosis, left ventricular ejection fraction, and infarct size. Results: By intention-to-treat analysis, patients randomly assigned to omega-3 fatty acids experienced a significant reduction of left ventricular systolic volume index (–5.8%, P=0.017), and noninfarct myocardial fibrosis (–5.6%, P=0.026) in comparison with placebo. Per-protocol analysis revealed that those patients who achieved the highest quartile increase in red blood cell omega-3 index experienced a 13% reduction in left ventricular systolic volume index in comparison with the lowest quartile. In addition, patients in the omega-3 fatty acid arm underwent significant reductions in serum biomarkers of systemic and vascular inflammation and myocardial fibrosis. There were no adverse events associated with high-dose omega-3 fatty acid therapy. Conclusions: Treatment of patients with acute myocardial infarction with high-dose omega-3 fatty acids was associated with reduction of adverse left ventricular remodeling, noninfarct myocardial fibrosis, and serum biomarkers of systemic inflammation beyond current guideline-based standard of care. Clinical Trial Registration: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00729430.

Characterization of subacute and convalescent fibrotic burden in the remote myocardium after acute infarction provides strong and incremental prediction of changes in left and right functions and final infarct size, incremental to knowledge of the subacute infarct size

Summary To test the hypothesis that fibrotic burden in remote myocardium quantified by CMR during early period of infarct healing is a strong determinant of the cardiac remodeling outcome. Background After acute myocardial infarction (AMI), co-existing myocardial stunning, ischemia, and architectural alteration may yield variable patterns of ventricular remodeling with potential long-term prognostic implications. We hypothesize that CMR quantification of fibrotic content, based on R1 (1/T1) assessment, in non-infarct myocardium early after infarction and during the infarct healing phases may provide novel prediction of the final infarct size and alteration of ventricular functions during infarct healing. Methods

CMR quantification of infarct tissue heterogeneity and remote myocardial fibrotic burden during convalescent phase following acute myocardial infarction (MI) provided strong and complementary evidence of ventricular arrhythmogenicity from quantitative microvolt T-wave alternans testing (the NHLBI PROSPECT-CMR study)

In patients with recent MI, elevated fibrotic burden within the remote myocardium quantified by CMR is strongly associated with post-exercise heart rate variability (HRV) and QT dispersion (QTD). In contrast, infarct tissue heterogeneity demonstrated strong association with prolonged mean QRS duration at rest and during exercise. We postulate that these patterns of ischemic structural/arrhythmogenic affiliations during convalescent infarct healing, likely reflect differences in depolarization/repolarization characteristics of different post-ischemic myocardium and sympathetic innervation.

Fibrotic content of LV myocardium quantified by CMR characterizes left atrial sizes and total left atrial emptying function incremental to LV functional parameters and LV myocardial mass index in patients with hypertrophic cardiomyopathy

Fibrotic burden of LV myocardium quantified by CMR provides additional information about LA size and mechanics than morphological severity of LV hypertrophy measured by LV mass index alone.

Infarct tissue heterogeneity by contrast-enhanced MRI is a novel predictor of mortality in patients with coronary artery disease with reduced left ventricular systolic function

While LVEF is the current most robust marker of mortality in pts with chronic CAD, an improved risk stratification method is necessary for guidance of medical or ICD therapy. Peri-infarct zone (PIZ) as a marker of infarcted heterogeneity has been associated with arrythmogenic substrates and reduced post-MI survival. However, the prognostic implication of PIZ has not been studied in a large cohort of CAD pts with long-term follow-up. In addition, whether this prognostic value of PIZ maintains among different LVEF categories is unknown.

Prediction of modifications in size and peri-infarct zone by T2-imaging after an acute myocardial infarction during longitudinal follow-up by cardiac MRI

Background Fat suppressed T2-weighted black blood turbo spin echo (BBTSE) imaging can detect myocardial edema developed after acute myocardial infarction (MI) and characterize the extent of myocardium at risk in comparison to late gadolinium enhancement (LGE) imaging. Purpose We hypothesized that T2-extent at baseline and changes during follow-up are associated with dynamic changes of infarct heterogeneity during the convalescence phase of infarct healing. We further explored the strength of association in quantifying T2-based myocardial edema, using a semi-automated method and manual tracing. Methods Fifty-one patients (40 men) underwent 3T cardiac MRI both at 18±10 days and 7.7±1.1 months after an acute MI, including: 3 short-axis slices of T2-weighted fat-suppressed BBTSE, LV function assessment by SSFP and LGE imaging. Area of hyperintensity on T2 images was assessed by a semi-automated method using a threshold of mean signal intensity in the remote ROI ± 2 SD and by manual tracing. In further analyses, correlations of T2 extent, expressed as the percentage of total myocardium, and other MRI results were assessed by Spearman correlation. Results Correlations between the T2 extent, LV parameters, infarct heterogeneity and their respective changes are displayed in the table. At baseline, hyperintense T2 myocardium was demonstrated in 50 patients (98%) and represented 20.5±14.0% of total myocardium. Baseline T2 size was inversely correlated with LVEF and was directly correlated with total MI size. Hyperintense T2 areas persisted in 12 patients (24%) at follow-up. Manual-tracing was correlated well with the semi-automated method (Spearman’s rho 0.84; P<0.0001). Table 1