Idan Roifman

Hyperpolarized 13C Metabolic MRI of the Human HeartNovelty and Significance

Rationale: Altered cardiac energetics is known to play an important role in the progression toward heart failure. A noninvasive method for imaging metabolic markers that could be used in longitudinal studies would be useful for understanding therapeutic approaches that target metabolism. Objective: To demonstrate the first hyperpolarized 13C metabolic magnetic resonance imaging of the human heart. Methods and Results: Four healthy subjects underwent conventional proton cardiac magnetic resonance imaging followed by 13C imaging and spectroscopic acquisition immediately after intravenous administration of a 0.1 mmol/kg dose of hyperpolarized [1-13C]pyruvate. All subjects tolerated the procedure well with no adverse effects reported ≤1 month post procedure. The [1-13C]pyruvate signal appeared within the chambers but not within the muscle. Imaging of the downstream metabolites showed 13C-bicarbonate signal mainly confined to the left ventricular myocardium, whereas the [1-13C]lactate signal appeared both within the chambers and in the myocardium. The mean 13C image signal:noise ratio was 115 for [1-13C]pyruvate, 56 for 13C-bicarbonate, and 53 for [1-13C]lactate. Conclusions: These results represent the first 13C images of the human heart. The appearance of 13C-bicarbonate signal after administration of hyperpolarized [1-13C]pyruvate was readily detected in this healthy cohort (n=4). This shows that assessment of pyruvate metabolism in vivo in humans is feasible using current technology. Clinical Trial Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT02648009.Rationale: Altered cardiac energetics is known to play an important role in the progression toward heart failure. A noninvasive method for imaging metabolic markers that could be used in longitudinal studies would be useful for understanding therapeutic approaches that target metabolism. Objective: To demonstrate the first hyperpolarized 13 C metabolic magnetic resonance imaging of the human heart. Methods and Results: Four healthy subjects underwent conventional proton cardiac magnetic resonance imaging followed by 13 C imaging and spectroscopic acquisition immediately after intravenous administration of a 0.1 mmol/kg dose of hyperpolarized [1- 13 C]pyruvate. All subjects tolerated the procedure well with no adverse effects reported ≤1 month post procedure. The [1- 13 C]pyruvate signal appeared within the chambers but not within the muscle. Imaging of the downstream metabolites showed 13 C-bicarbonate signal mainly confined to the left ventricular myocardium, whereas the [1- 13 C]lactate signal appeared both within the chambers and in the myocardium. The mean 13 C image signal:noise ratio was 115 for [1- 13 C]pyruvate, 56 for 13 C-bicarbonate, and 53 for [1- 13 C]lactate. Conclusions: These results represent the first 13 C images of the human heart. The appearance of 13 C-bicarbonate signal after administration of hyperpolarized [1- 13 C]pyruvate was readily detected in this healthy cohort (n=4). This shows that assessment of pyruvate metabolism in vivo in humans is feasible using current technology. Clinical Trial Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT02648009.

Coarctation of the Aorta and Coronary Artery Disease: Fact or Fiction?

Background— Aortic coarctation (CoA) is reported to predispose to coronary artery disease (CAD). However, our clinical observations do not support this premise. Our objectives were to describe the prevalence of CAD among adults with CoA and to determine whether CoA is an independent predictor of CAD or premature CAD. Methods and Results— The study population was derived from the Quebec Congenital Heart Disease Database. We compared patients with CoA and those with a ventricular septal defect, who are not known to be at increased risk of CAD. The prevalence of CAD in patients with CoA compared with those with ventricular septal defect was determined. We then used a nested case-control design to determine whether CoA independently predicted for the development of CAD. Of 756 patients with CoA who were alive in 2005, 37 had a history of CAD compared with 224 of 6481 patients with ventricular septal defect (4.9% versus 3.5%; P=0.04). Male sex (odds ratio [OR], 2.13; 95% confidence interval [CI], 1.62–2.80), hypertension (OR, 1.95; 95% CI, 1.44–2.64), diabetes mellitus (OR, 1.68; 95% CI, 1.09–2.58), age (OR per 10-year increase, 2.28; 95% CI, 2.09–2.48), and hyperlipidemia (OR, 11.58; 95% CI, 5.75–23.3) all independently predicted for the development of CAD. CoA did not independently predict for the development of CAD (OR, 1.04; 95% CI, 0.68–1.57) or premature CAD (OR for CoA versus ventricular septal defect, 1.44; 95% CI, 0.79–2.64) after adjustment for other factors. Conclusions— Although traditional cardiovascular risk factors independently predicted for the development of CAD, the diagnosis of CoA alone did not. Our findings suggest that cardiovascular outcomes of these patients may be improved with tight risk factor control.

Comparison of hemodynamic performance of self-expandable CoreValve versus balloon-expandable Edwards SAPIEN aortic valves inserted by catheter for aortic stenosis.

Transcatheter aortic valve implantation with the self-expandable CoreValve (CV) and the balloon-expandable Edwards SAPIEN (ES) bioprostheses has been widely used for the treatment of severe aortic stenosis. However, a direct comparison of the hemodynamic results associated with these 2 prostheses is lacking. The aim of the present study was to compare the hemodynamic performance of both bioprostheses. A total of 41 patients who underwent transcatheter aortic valve implantation with the CV prosthesis were matched 1:1 for prosthesis size (26 mm), aortic annulus size, left ventricular ejection fraction, body surface area, and body mass index with patients who underwent transcatheter aortic valve implantation with the ES prosthesis. Doppler-echocardiographic data were prospectively collected before the intervention and at hospital discharge, and all examinations were sent to, and analyzed in, a central echocardiography core laboratory. The mean transprosthetic residual gradient was lower (p = 0.024) in the CV group (7.9 ± 3.1 mm Hg) than in the ES group (9.7 ± 3.8 mm Hg). The effective orifice area tended to be greater in the CV group (1.58 ± 0.31 cm(2) vs 1.49 ± 0.24 cm(2), p = 0.10). The incidence of severe prosthesis-patient mismatch was, however, similar between the 2 groups (effective orifice area indexed to the body surface area ≤0.65 cm(2)/m(2); CV 9.8%, ES 9.8%, p = 1.0). The incidence of paravalvular aortic regurgitation was greater with the CV (grade 1 or more in 85.4%, grade 2 or more in 39%) than with the ES (grade 1 or more in 58.5%, grade 2 or more in 22%; p = 0.001). The number and extent of paravalvular leaks were greater in the CV group (p <0.01 for both comparisons). In conclusion, transcatheter aortic valve implantation with the CV prosthesis was associated with a lower residual gradient but a greater rate of paravalvular aortic regurgitation compared to the ES prosthesis. The potential clinical consequences of the differences in hemodynamic performance between these transcatheter heart valves needs to be addressed in future studies.

Hyperpolarized 13C Metabolic MRI of the Human Heart: Initial Experience.

Rationale: Altered cardiac energetics is known to play an important role in the progression toward heart failure. A noninvasive method for imaging metabolic markers that could be used in longitudinal studies would be useful for understanding therapeutic approaches that target metabolism. Objective: To demonstrate the first hyperpolarized 13C metabolic magnetic resonance imaging of the human heart. Methods and Results: Four healthy subjects underwent conventional proton cardiac magnetic resonance imaging followed by 13C imaging and spectroscopic acquisition immediately after intravenous administration of a 0.1 mmol/kg dose of hyperpolarized [1-13C]pyruvate. All subjects tolerated the procedure well with no adverse effects reported ≤1 month post procedure. The [1-13C]pyruvate signal appeared within the chambers but not within the muscle. Imaging of the downstream metabolites showed 13C-bicarbonate signal mainly confined to the left ventricular myocardium, whereas the [1-13C]lactate signal appeared both within the chambers and in the myocardium. The mean 13C image signal:noise ratio was 115 for [1-13C]pyruvate, 56 for 13C-bicarbonate, and 53 for [1-13C]lactate. Conclusions: These results represent the first 13C images of the human heart. The appearance of 13C-bicarbonate signal after administration of hyperpolarized [1-13C]pyruvate was readily detected in this healthy cohort (n=4). This shows that assessment of pyruvate metabolism in vivo in humans is feasible using current technology. Clinical Trial Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT02648009.Rationale: Altered cardiac energetics is known to play an important role in the progression toward heart failure. A noninvasive method for imaging metabolic markers that could be used in longitudinal studies would be useful for understanding therapeutic approaches that target metabolism. Objective: To demonstrate the first hyperpolarized 13 C metabolic magnetic resonance imaging of the human heart. Methods and Results: Four healthy subjects underwent conventional proton cardiac magnetic resonance imaging followed by 13 C imaging and spectroscopic acquisition immediately after intravenous administration of a 0.1 mmol/kg dose of hyperpolarized [1- 13 C]pyruvate. All subjects tolerated the procedure well with no adverse effects reported ≤1 month post procedure. The [1- 13 C]pyruvate signal appeared within the chambers but not within the muscle. Imaging of the downstream metabolites showed 13 C-bicarbonate signal mainly confined to the left ventricular myocardium, whereas the [1- 13 C]lactate signal appeared both within the chambers and in the myocardium. The mean 13 C image signal:noise ratio was 115 for [1- 13 C]pyruvate, 56 for 13 C-bicarbonate, and 53 for [1- 13 C]lactate. Conclusions: These results represent the first 13 C images of the human heart. The appearance of 13 C-bicarbonate signal after administration of hyperpolarized [1- 13 C]pyruvate was readily detected in this healthy cohort (n=4). This shows that assessment of pyruvate metabolism in vivo in humans is feasible using current technology. Clinical Trial Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT02648009.

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.

Correlation of late gadolinium enhancement MRI and quantitative T2 measurement in cardiac sarcoidosis

To investigate the potentially improved detection and quantification of cardiac involvement using novel late‐gadolinium‐enhancement (LGE) cardiac magnetic resonance imaging (MRI) and quantitative T2 measurement to achieve better myocardial tissue characterization in systemic sarcoidosis.

Temporal Trends in the Utilization of Noninvasive Diagnostic Tests for Coronary Artery Disease in Ontario Between 2008 and 2014: A Population-Based Study

The proliferation of cardiac diagnostic tests over the past few decades has received substantial attention from policymakers. However, contemporary population-based temporal trends of the utilization of noninvasive cardiac diagnostic tests for coronary artery disease are not known. Our objective was to examine the temporal trends in the utilization of coronary computed tomography angiography (CCTA), myocardial perfusion imaging (MPI), exercise stress testing (GXT), and stress echocardiography between 2008 and 2014. We performed a population-based repeated cross-sectional study of the adult population of Ontario between January 1, 2008 and December 31, 2014. Annual utilization rates of noninvasive cardiac diagnostic tests were computed. For each cardiac testing modality, a negative binomial regression model was used to assess temporal changes in test utilization. GXT and MPI collectively accounted for 88% of all cardiac noninvasive diagnostic tests throughout our study period. Age- and sex-standardized rates of GXT declined from 26.7/1000 adult population to 21.6/1000 adult population (mean annual reduction of 3.4%; P < 0.001). MPI rates declined from 21.1/1000 adult population to 19.5/1000 adult population (mean annual reduction of 1.3%; P < 0.001). Although utilization rates for both CCTA and stress echocardiography increased over time, the combined rate of all available tests decreased from 50.8/1000 adult population to 49.1/1000 adult population (mean annual reduction of 1.1%; P < 0.001). In conclusion, utilization rates for the most prevalent noninvasive cardiac diagnostic tests-GXT and MPI-declined over our study period. Furthermore, the overall test utilization rate also declined over time. We believe our findings are encouraging from a health policy perspective. Nonetheless, rising utilization rates for CCTA and stress echocardiography will need to be monitored in the future.

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.

Association between publication of appropriate use criteria and the temporal trends in diagnostic angiography in stable coronary artery disease: A population-based study

BACKGROUND The appropriate use criteria (AUC) were developed to aid clinicians in making clinical decisions regarding coronary angiography. The aim of the present study was to evaluate the association between the publication of the AUC criteria in diagnostic angiography and rates of angiography in Ontario. METHODS Our cohort consisted of all patients who underwent coronary angiography in Ontario from 1st October 2008 to 31st October 2013 for the indication of suspected stable coronary artery disease. We determined monthly age- and sex-standardized rates of angiography per 100,000 adults. To determine the association between the publication of the AUC for diagnostic angiograms and the rates of angiography, we conducted a time series analysis using an autoregressive integrated moving average model. As a sensitivity analyses, we evaluated the impact of the AUC on the rates of percutaneous coronary intervention (PCI) per 100 angiograms. RESULTS We included 114,551 angiograms for stable coronary artery disease. In the period prior to the publication of the AUC, the average monthly age- and sex-standardized rate of angiography was 18.7 per 100,000; post-AUC, the average monthly rate decreased to 17.6 per 100,000 adults (P = .037). In contrast, in the 29,358 PCIs included in the analysis, the monthly PCI rates per 100 angiograms were unchanged (25.2 pre-AUC; 26.8 post-AUC; P = .29). In the sensitivity analysis, the rate of appropriate/inappropriate and uncertain indication did not significantly change over the study period. CONCLUSIONS The publication of the diagnostic angiography AUC criteria was associated with a decrease in the population rates of diagnostic angiography. This suggests that the AUC potentially was associated with an increased threshold to pursue invasive diagnostic testing.