Kim A Connelly

Hyperpolarized (13)C magnetic resonance reveals early- and late-onset changes to in vivo pyruvate metabolism in the failing heart.

Impaired energy metabolism has been implicated in the pathogenesis of heart failure. Hyperpolarized 13C magnetic resonance (MR), in which 13C‐labelled metabolites are followed using MR imaging (MRI) or spectroscopy (MRS), has enabled non‐invasive assessment of pyruvate metabolism. We investigated the hypothesis that if we serially examined a model of heart failure using non‐invasive hyperpolarized [13C]pyruvate with MR, the profile of in vivo pyruvate oxidation would change throughout the course of the disease.

Alternative Imaging Modalities in Ischemic Heart Failure (AIMI-HF) IMAGE HF Project I-A: study protocol for a randomized controlled trial

BackgroundIschemic heart disease (IHD) is the most common cause of heart failure (HF); however, the role of revascularization in these patients is still unclear. Consensus on proper use of cardiac imaging to help determine which candidates should be considered for revascularization has been hindered by the absence of clinical studies that objectively and prospectively compare the prognostic information of each test obtained using both standard and advanced imaging.Methods/DesignThis paper describes the design and methods to be used in the Alternative Imaging Modalities in Ischemic Heart Failure (AIMI-HF) multi-center trial. The primary objective is to compare the effect of HF imaging strategies on the composite clinical endpoint of cardiac death, myocardial infarction (MI), cardiac arrest and re-hospitalization for cardiac causes.In AIMI-HF, patients with HF of ischemic etiology (n = 1,261) will follow HF imaging strategy algorithms according to the question(s) asked by the physicians (for example, Is there ischemia and/or viability?), in agreement with local practices. Patients will be randomized to either standard (SPECT, Single photon emission computed tomography) imaging modalities for ischemia and/or viability or advanced imaging modalities: cardiac magnetic resonance imaging (CMR) or positron emission tomography (PET). In addition, eligible and consenting patients who could not be randomized, but were allocated to standard or advanced imaging based on clinical decisions, will be included in a registry.DiscussionAIMI-HF will be the largest randomized trial evaluating the role of standard and advanced imaging modalities in the management of ischemic cardiomyopathy and heart failure. This trial will complement the results of the Surgical Treatment for Ischemic Heart Failure (STICH) viability substudy and the PET and Recovery Following Revascularization (PARR-2) trial. The results will provide policy makers with data to support (or not) further investment in and wider dissemination of alternative ‘advanced’ imaging technologies.Trial registrationNCT01288560

Echocardiography vs. Cardiac Magnetic Resonance Imaging for the Diagnosis of Left Ventricular Thrombus: A Systematic Review.

BACKGROUND Left ventricular (LV) thrombi can occur in the setting of LV dysfunction especially in the acute postmyocardial infarction period. The ideal imaging strategy to detect LV thrombi is currently unknown. The objective of this study was to conduct a systematic review to compare the accuracy of transthoracic echocardiography (TTE) with that of cardiac magnetic resonance (CMR) imaging for the detection of LV thrombi. METHODS OvidMEDLINE, EMBASE, and Cochrane databases were searched for articles published between January 1, 1946 and July 31, 2013. After screening of all potentially relevant abstracts and articles, 7 studies were ultimately selected for this review. RESULTS Our results suggest that late gadolinium enhancement CMR imaging is the most accurate modality for the detection of LV thrombi (sensitivity 88%, specificity 99%), followed by cine-CMR imaging (sensitivity 58%-79%, specificity 99%, accuracy 95%, positive predictive value 93%-95%, negative predictive value 95%-96%), contrast TTE (sensitivity 23%-61%, specificity 96%-99%, accuracy 92%, positive predictive value 93%, negative predictive value 91%), and, finally, noncontrast TTE (sensitivity 24%-33%, specificity 94%-95%, accuracy 82%, positive predictive value 57%, negative predictive value 85%). Accuracy of TTE might be improved if a clear clinical indication is provided and with routine use of LV opacifying contrast agents. CONCLUSIONS Our findings indicate that late gadolinium enhancement CMR imaging is the most accurate sequence in the detection of LV thrombus, and should be favoured when there is a high index of suspicion. When CMR is contraindicated, unavailable, or impractical, our analysis argues for contrast-TTE in patients at high risk for developing LV thrombi.

Pattern Recognition of Abnormal Left Ventricle Wall Motion in Cardiac MR

There are four main problems that limit application of pattern recognition techniques for recognition of abnormal cardiac left ventricle (LV) wall motion: (1) Normalization of the LVs size, shape, intensity level and position; (2) defining a spatial correspondence between phases and subjects; (3) extracting features; (4) and discriminating abnormal from normal wall motion. Solving these four problems is required for application of pattern recognition techniques to classify the normal and abnormal LV wall motion. In this work, we introduce a normalization scheme to solve the first and second problems. With this scheme, LVs are normalized to the same position, size, and intensity level. Using the normalized images, we proposed an intra-segment classification criterion based on a correlation measure to solve the third and fourth problems. Application of the method to recognition of abnormal cardiac MR LV wall motion showed promising results.

Thrombus aspiration during primary percutaneous coronary intervention is associated with reduced myocardial edema, hemorrhage, microvascular obstruction and left ventricular remodeling

BackgroundThrombus aspiration (TA) has been shown to improve microvascular perfusion during primary percutaneous coronary intervention (PCI) for patients with ST-segment elevation myocardial infarction (STEMI). The objective of our study was to assess the relationship between TA and myocardial edema, myocardial hemorrhage, microvascular obstruction (MVO) and left ventricular remodeling in STEMI patients using cardiovascular magnetic resonance (CMR).MethodsSixty patients were enrolled post primary PCI and underwent CMR on a 1.5 T scanner at 48 hours and 6 months. Patients were retrospectively stratified into 2 groups: those that received TA (35 patients) versus that did not receive thrombus aspiration (NTA) (25 patients). Myocardial edema and myocardial hemorrhage were assessed by T2 and T2* quantification respectively. MVO was assessed via a contrast-enhanced T1-weighted inversion recovery gradient-echo sequence.ResultsAt 48 hours, infarct segment T2 (NTA 57.9 ms vs. TA 52.1 ms, p = 0.022) was lower in the TA group. Also, infarct segment T2* was higher in the TA group (NTA 29.3 ms vs. TA 37.8 ms, p = 0.007). MVO incidence was lower in the TA group (NTA 88% vs. TA 54%, p = 0.013).At 6 months, left ventricular end-diastolic volume index (NTA 91.9 ml/m2 vs. TA 68.3 ml/m2, p = 0.013) and left ventricular end systolic volume index (NTA 52.1 ml/m2 vs. TA 32.4 ml/m2, p = 0.008) were lower and infarct segment systolic wall thickening was higher in the TA group (NTA 3.5% vs. TA 74.8%, p = 0.003).ConclusionTA during primary PCI is associated with reduced myocardial edema, myocardial hemorrhage, left ventricular remodeling and incidence of MVO after STEMI.

Comparison of the frequencies of myocardial edema determined by cardiac magnetic resonance in diabetic versus nondiabetic patients having percutaneous coronary intervention for ST elevation myocardial infarction.

The specific mechanisms by which diabetes may affect the myocardial tissue response to ischemia are unclear. Our objective was to prospectively quantify the degree of myocardial edema in diabetics versus nondiabetics with ST elevation myocardial infarction using cardiac magnetic resonance. Fifty-two patients (16 diabetics and 36 nondiabetics) were enrolled after primary percutaneous coronary intervention and underwent cardiac magnetic resonance on a 1.5-T scanner at 48 hours and 6 months. Myocardial edema was quantified using a T2 mapping technique, and infarct size and microvascular obstruction size were assessed by way of a contrast-enhanced T1-weighted inversion recovery gradient-echo sequence. The infarct segment T2 was elevated in diabetics compared with nondiabetics (59.0 ± 8.0 vs 50.8 ± 3.1 ms, p <0.001) at 48 hours. Multivariate analysis demonstrated that diabetes (p <0.001) and symptom-to-balloon time (p = 0.04) were independent predictors of the degree of acute myocardial edema. Infarct size was nonsignificantly higher in the diabetic group at 48 hours (26.9 ± 9.4% vs 20.1 ± 10.1% of myocardium, p = 0.07) and 6 months (17.1 ± 6.3% vs 13.4 ± 6.1% of myocardium, p = 0.09). Microvascular obstruction size was equivalent in both groups, and there was a trend toward lower myocardial salvage index in diabetics (34.2 ± 11.8 vs 49.6 ± 13.4, p = 0.08). In conclusion, diabetes is associated with increased myocardial edema in the acute phase after primary percutaneous coronary intervention. Our results offer insight into the complex processes that characterize myocardial tissue response to injury in diabetic patients.

The Effect of Percutaneous Coronary Intervention of Chronically Totally Occluded Coronary Arteries on Left Ventricular Global and Regional Systolic Function

BACKGROUND Percutaneous coronary intervention (PCI) is frequently attempted to open chronic total occlusions (CTOs) and restore epicardial coronary flow. Data suggest adverse outcomes in the case of PCI failure. We hypothesized that failure to open a CTO might adversely affect regional cardiac function and promote deleterious cardiac remodelling, and success would improve global and regional cardiac function assessed using cardiac magnetic resonance and velocity vector imaging. METHODS Thirty patients referred for PCI to a CTO underwent cardiac magnetic resonance examination before and after the procedure. Left ventricular function and transmural extent of infarction was assessed in these patients. Regional cardiac function using Velocity Vector Imaging version 3.0.0 (Siemens) was assessed in 20 patients. RESULTS Successful CTO opening (thrombolysis in myocardial infarction 3 flow) occurred in 63% of patients. Left ventricular ejection fraction significantly increased after successful PCI (50 ± 13% to 54 ± 11%; P < 0.01). Global longitudinal strain (GLS) fell significantly in the failed group (Δ = -25 ± 17%; P = 0.02) in contrast with successful PCI in which GLS did not change (Δ 20 ± 32%; P = 0.17). GLS rate followed a pattern similar to GLS (failed, Δ -30 ± 17%; P < 0.01 vs success Δ 25 ± 48%; P = 0.34). In contrast, radial and circumferential strain/strain rate were not different between groups after success/failed PCI. CONCLUSIONS Regional cardiac function assessment using velocity vector imaging showed a significant decline in GLS and GLS rate in patients in whom PCI failed to open a CTO, with no change in global measures of cardiac function.

Evolution of right ventricular function post‐acute ST elevation myocardial infarction

To characterize the evolution of right ventricular (RV) function post‐myocardial infarction (MI), to describe the culprit vessel involved with RV injury and to assess the concordance between RV injury on magnetic resonance imaging (MRI) and RV infarct on electrocardiogram (EKG).

Prognostic value of myocardial T2 mapping post reperfused acute myocardial infarction

Methods Fifty-four patients were enrolled post primary percutaneous coronary intervention (PCI) and underwent CMR on a 1.5T scanner at 48 hours. Myocardial edema was quantified using a T2 mapping technique, while infarct size was assessed via a contrast-enhanced T1-weighted inversion recovery gradient-echo sequence. Information regarding four clinical outcomes: a) mortality, b) repeat myocardial infarction, c) heart failure hospitalization and d) repeat revascularization was collected at 12 months post index primary PCI. Our primary clinical endpoint was a composite of these 4 outcome measures of major adverse cardiovascular events (MACE). The Cox proportional hazards regression model was used to calculate the relative risk of MACE for increased T2 values, adjusted for baseline characteristics related to increased edema (diabetes status, symptom to balloon time, infarct size). Results The mean age was 59.6 ± 8.2 years, 88% were males, 35% were diabetics, 44% were hypertensive. The mean symptom to balloon time was 395 ± 230 minutes and mean door to balloon time was 81.5 ± 39 minutes. The mean T2 value was higher in the infarct segment compared to remote segment (55.1 ± 7.6 ms vs 40.2 ± 2.6 ms, p<0.001). Patients with MACE (n=12) had higher infarct segment T2 values compared to patients that did not (64.4 ± 7.3 ms vs 51.1 ± 5.8 ms, p<0.001). After adjustment for variables associated with increased edema, a T2 value of ≥ 62 ms was associated with a hazard ratio of 1.04 (95% CI:1.01-1.07, p=0.009) for MACE at 12 months (Table 1). Conclusions In reperfused STEMI patients, higher T2 values in the infarct segment are associated with worse prognosis. This suggests the need to develop therapies aimed at reducing myocardial edema post acute myocardial infarction.

The non-glycemic effects of incretin therapies on cardiovascular outcomes, cognitive function and bone health

The incretin therapies, glucagon-like peptide-1 receptor agonists and dipeptidyl-peptidase-4 inhibitors, have been developed to lower blood glucose levels in patients with Type 2 diabetes. However, in addition to being a treatment strategy to improve metabolic control, incretin therapies have shown effects independent of glycemic control, including the potential to positively impact cardiovascular events, cognitive deficits and bone mineral density. This paper outlines the non-glycemic effects of incretin therapies on cardiovascular disease, cognitive function and bone health.