Serial Cardiac Magnetic Resonance Research Articles

Myocardial Biopsy in a History of Light-Chain Amyloidosis Patient With Serial Cardiac Magnetic Resonance Imaging Not Suggestive of Cardiac Involvement.

Myocardial Biopsy in a History of Light-Chain Amyloidosis Patient With Serial Cardiac Magnetic Resonance Imaging Not Suggestive of Cardiac Involvement.

Serial Magnetic Resonance Imaging to Identify Early Stages of Anthracycline-Induced Cardiotoxicity

BackgroundAnthracycline-induced cardiotoxicity is a major clinical problem, and early cardiotoxicity markers are needed. ObjectivesThe purpose of this study was to identify early doxorubicin-induced cardiotoxicity by serial multiparametric cardiac magnetic resonance (CMR) and its pathological correlates in a large animal model. MethodsTwenty pigs were included. Of these, 5 received 5 biweekly intracoronary doxorubicin doses (0.45 mg/kg/injection) and were followed until sacrifice at 16 weeks. Another 5 pigs received 3 biweekly doxorubicin doses and were followed to 16 weeks. A third group was sacrificed after the third dose. All groups underwent weekly CMR examinations including anatomical and T2 and T1 mapping (including extracellular volume [ECV] quantification). A control group was sacrificed after the initial CMR. ResultsThe earliest doxorubicin-cardiotoxicity CMR parameter was T2 relaxation-time prolongation at week 6 (2 weeks after the third dose). T1 mapping, ECV, and left ventricular (LV) motion were unaffected. At this early time point, isolated T2 prolongation correlated with intracardiomyocyte edema secondary to vacuolization without extracellular space expansion. Subsequent development of T1 mapping and ECV abnormalities coincided with LV motion defects: LV ejection fraction declined from week 10 (2 weeks after the fifth and final doxorubicin dose). Stopping doxorubicin therapy upon detection of T2 prolongation halted progression to LV motion deterioration and resolved intracardiomyocyte vacuolization, demonstrating that early T2 prolongation occurs at a reversible disease stage. ConclusionsT2 mapping during treatment identifies intracardiomyocyte edema generation as the earliest marker of anthracycline-induced cardiotoxicity, in the absence of T1 mapping, ECV, or LV motion defects. The occurrence of these changes at a reversible disease stage shows the clinical potential of this CMR marker for tailored anthracycline therapy.

A Novel Atlas-Based Strategy for Understanding Cardiac Dysfunction in Patients with Congenital Heart Disease

Tetralogy of Fallot (TOF) is the most common form of cyanotic congenital heart disease. Infants diagnosed with TOF require surgical interventions to survive into adulthood. However, as a result of postoperative structural malformations and long-term ventricular remodeling, further interventions are often required later in life. To help identify those at risk of disease progression, serial cardiac magnetic resonance (CMR) imaging is used to monitor these patients. However, most of the detailed information on cardiac shape and biomechanics contained in these large four-dimensional (4D) data sets goes unused in clinical practice for lack of efficient and comprehensive quantitative analysis tools. While current global metrics of cardiac size and function, such as indexed ventricular mass and volumes, can identify patients at risk of further complications, they are not adequate to explain the underlying mechanisms causing the postoperative malfunctions, and help cardiologists plan optimal personalized treatments. We are proposing a novel approach that uses 4D ventricular shape models derived from CMR imaging exams to generate statistical atlases of ventricular shape and finite-element models of ventricular biomechanics to identify specific features of cardiac shape and biomechanical properties that explain variations in ventricular function. This study has the potential to discover novel biomarkers that precede adverse ventricular remodeling and dysfunction.

Multimodality imaging, single center, cross-sectional study in adolescents or young adults with repaired tetralogy of Fallout.

Proper integration of multiple imaging modalities in the routine follow-up of patients with repaired tetralogy of Fallout (TOF) is poorly supported by data. We report our single center comparative study between cardiac magnetic resonance (CMR) and echocardiography to assess equipoise in the clinical utility of these two imaging methods in an unselected consecutive cohort of TOF patients referred to our outpatient clinic. In this cross-sectional study, repaired TOF patients who underwent CMR and echocardiography within a 4-week period between 2010 and 2011 at our Center were included. Linear regression was used to analyze degree of inter modality correlation. A prediction model tested the association between functional data/probrain natriuretic peptide (Pro-BNP) with CMR. Fifty patients were included in the study (mean age 31 ± 18 years). The best predictors of right ventricle (RV) ejection fraction at CMR were tricuspid anular plane systolic excursion (tricuspid valve anular plane systolic excursion, R 0.37, P < 0.0001) and RV peak S-wave velocity (R 0.40, P < 0.001). Pro-BNP levels did present weak correlation with New York Heart Association functional class (R 0.31, P < 0.002) and QRS duration (R 0.32, P < 0.002) and a moderate correlation with right atrium area at CMR (R 0.46, P < 0.0001). We found limited correlation between the two imaging modalities in the evaluation of RV after intracardiac repair of TOF. Pro-BNP level presents moderate correlation with right atrium area measured with echocardiography. Serial CMR evaluations are needed in this patient population, but they may be interchanged by routine echocardiography in particular in patients with normal or stable echocardiographic parameters.

Progression of myocardial fibrosis in hypertrophic cardiomyopathy: mechanisms and clinical implications.

AimsMyocardial fibrosis as detected by late gadolinium enhancement (LGE) on cardiac magnetic resonance (CMR) is a powerful prognostic marker in hypertrophic cardiomyopathy (HCM) and may be progressive. The precise mechanisms underlying fibrosis progression are unclear. We sought to assess the extent of LGE progression in HCM and explore potential causal mechanisms and clinical implications.Methods and resultsSeventy-two HCM patients had two CMR (CMR1-CMR2) at an interval of 5.7 ± 2.8 years with annual clinical follow-up for 6.3 ± 3.6 years from CMR1. A combined endpoint of heart failure progression, cardiac hospitalization, and new onset ventricular tachycardia was assessed. Cine and LGE imaging were performed to assess left ventricular (LV) mass, function, and fibrosis on serial CMR. Stress perfusion imaging and cardiac energetics were undertaken in 38 patients on baseline CMR (CMR1). LGE mass increased from median 4.98 g [interquartile range (IQR) 0.97–13.48 g] to 6.30 g (IQR 1.38–17.51 g) from CMR1 to CMR2. Substantial LGE progression (ΔLGE ≥ 4.75 g) occurred in 26% of patients. LGE increment was significantly higher in those with impaired myocardial perfusion reserve (<MPRI 1.40) and energetics (phosphocreatine/adenosine triphosphate <1.44) on baseline CMR (P ≤ 0.01 for both). Substantial LGE progression was associated with LV thinning, increased cavity size and reduced systolic function, and conferred a five-fold increased risk of subsequent clinical events (hazard ratio 5.04, 95% confidence interval 1.85–13.79; P = 0.002).ConclusionMyocardial fibrosis is progressive in some HCM patients. Impaired energetics and perfusion abnormalities are possible mechanistic drivers of the fibrotic process. Fibrosis progression is associated with adverse cardiac remodelling and predicts an increased risk of subsequent clinical events in HCM.

Use of integrated imaging and serum biomarker profiles to identify subclinical dysfunction in pediatric cancer patients treated with anthracyclines

BackgroundAnthracycline induced cardiomyopathy is a major cause of mortality and morbidity among pediatric cancer survivors. It has been postulated that oxidative stress induction and inflammation may play a role in the pathogenesis of this process. Accordingly, the present study performed an assessment of biomarker profiles and functional imaging parameters focused upon potential early determinants of anthracycline induced cardiomyopathy.MethodsPatients (10–22 years) were prospectively enrolled between January 2013 and November 2014. Thirteen subjects completed the study and underwent serial cardiac magnetic resonance imaging and plasma biomarker profiling performed 24–48 h after the first anthracycline dose and at set dose intervals. In addition, we collected plasma samples from 62 healthy controls to examine normal plasma biomarker profiles.ResultsLeft ventricular ejection fraction (LVEF) decreased from 64.3 ± 6.2 at the first visit to 57.5 ± 3.3 (p = 0.004) 1 year after chemotherapy. A decline in longitudinal strain magnitude occurred at lower cumulative doses. A differential inflammatory/matrix signature emerged in anthracycline induced cardiomyopathy patients compared to normal including increased interleukin-8 and MMP levels. With longer periods of anthracycline dosing, MMP-7, a marker of macrophage proteolytic activation, increased by 165 ± 54% whereas interleukin-10 an anti-inflammatory marker decreased by 75 ± 13% (both p < 0.05). MMP7 correlated with time dependent changes in EF.ConclusionsAsymptomatic pediatric patients exposed to anthracycline therapy develop abnormal strain parameters at lower cumulative doses when compared to changes in EF. A differential biomarker signature containing both inflammatory and matrix domains occur early in anthracycline treatment. Dynamic changes in these domains occur with increased anthracycline doses and progression to anthracycline induced cardiomyopathy. These findings provide potential prognostic and mechanistic insights into the natural history of anthracycline induced cardiomyopathy.Trial registration numberNCT03211520 Date of Registration February 13, 2017, retrospectively registered.

Progressive right ventricular enlargement due to pulmonary regurgitation: Clinical characteristics of a “low-risk” group

BackgroundThe optimal interval between serial cardiac magnetic resonance imaging (CMRI) scans for monitoring right ventricular (RV) enlargement in the setting of severe pulmonic valve regurgitation (PR) is unknown. The purposes of this study were to (1) determine the annual change in RV volume on serial CMRI scans and (2) identify the risk factors for rapid progression of RV enlargement. MethodsA retrospective study of adults with postintervention native valve PR and ≥2 CMRI scans at Mayo Clinic Rochester from 2000 to 2015 was conducted. Rapid progression of RV enlargement was defined as first upper quartile of annual increase in RV end-diastolic volume index (RVEDVi) for the cohort. ResultsOf the 63 patients (age, 36 ± 9 years) in the study, 43 (68%) had tetralogy of Fallot, whereas 20 (32%) had valvular pulmonic stenosis. Right ventricular outflow tract interventions that resulted in PR were balloon pulmonary valvuloplasty (n = 4; 7%), transannular patch repair (n = 30; 58%), and nontransannular patch repair (n = 18; 35%). Interval between baseline and second CMRI was 2 (1-4) years. In comparison to baseline CMRI, RVEDVi increased from 130 (109-141) to 135 (126-155) mL/m2 and median annual change in RVEDVi was 3.1 (1.7-5.9) mL/m2. Univariate risk factors for rapid progression of RV enlargement (annual increase in RVEDVi >6 mL/m2) were ≥moderate tricuspid regurgitation and RVEDVi >130 mL/m2. Among the 24 patients without these risk factors (low-risk subgroup), RVEDVi increased by only 3 (0-7) mL/m2 over 7 (5-9) years. ConclusionsPatients with PR without RVEDVi >130 mL/m2 and/or ≥moderate tricuspid regurgitation represent a low-risk subgroup that may be appropriate for clinical and echo follow-up but may potentially require infrequent CMRI follow-up.

Effects of renal sympathetic denervation on myocardial structure, function and perfusion: A serial CMR study

Background and aimsEchocardiographic studies have shown improvements in cardiac indices associated with renal sympathetic denervation (RDN), however, the benefits on myocardial perfusion have never been assessed. This trial was designed to study the effects of RDN on myocardial perfusion using cardiac magnetic resonance (CMR) imaging. MethodsA total of 14 patients with resistant hypertension were recruited for RDN and myocardial perfusion, alongside other CMR indices, was assessed at baseline and at 6 months. ResultsRDN showed significant reduction of mean office blood pressures from 181/100 ± 19/16 mmHg to 147/85 ± 19/17 mmHg, 6 months after the procedure (p < 0.0001). This was combined with significant improvement in regional aortic distensibility (p < 0.02) and associated with trends of improved myocardial perfusion reserve index (baseline = 2.2 ± 1; 6 months = 2.9 ± 1 units) (p = 0.08). Left ventricular end systolic volume index decreased from baseline to 6 months post procedure, 27 ± 13 ml/m2vs. 22 ± 10 ml/m2 (p = 0.03), but there was no significant change in left ventricular end diastolic volume index (p = 0.09). There was significant improvement in mean left ventricular ejection fraction from 68 ± 10% to 72 + 9%, 6 months post procedure (p = 0.04). T1 mapping failed to detect fibrosis in these patients at baseline and therefore no change was noted, however, extracellular volume percent improved from 46 ± 4% at baseline to 41 ± 8% at 6 months (p = 0.002). ConclusionsThis study demonstrates that renal sympathetic denervation increased myocardial perfusion by 32% as assessed by CMR, and, this was associated with improvements in cardiac volumes and function. Larger well controlled and randomized studies are required to assess the clinical significance of these findings.

Atrial Infarction and Ischemic Mitral Regurgitation Contribute to Post-MI Remodeling of the Left Atrium

BackgroundLeft atrial (LA) remodeling after an acute myocardial infarction (MI) is poorly characterized regarding its determinants or its effect on ischemic mitral regurgitation (MR) development. ObjectivesThe purpose of this study was: 1) to compare LA structural remodeling in experimental MI swine models recapitulating the effects of left ventricular (LV) dysfunction, ischemic MR, and left atrial infarction (LAI); and 2) to analyze how LA remodeling influences ischemic MR development. MethodsThree models of MI were generated: 1) proximal left circumflex (LCx) coronary artery occlusion involving the LA branch (LAI group); 2) proximal LCx occlusion not involving the LA branch (LCx group); and 3) left anterior descending (LAD) occlusion (LAD group). Serial cardiac magnetic resonance scans were performed to define LA and LV remodeling and ischemic MR, and were correlated with histology. ResultsOcclusion of the LA branch (LAI group) induced a greater degree of LA dilation at 1 and 8 weeks post-MI than the LCx and LAD groups, along with early and severe impairment of LA function. In the LCx and LAD groups, LA dysfunction was less pronounced and not consistent. Development of ischemic MR was more pronounced in the LAI group than in the LCx group. Histology confirmed atrial infarction with extensive fibrosis in the LAI group and interstitial fibrosis in the LCx group. In the LAD group, LA remodeling was not observed by cardiac magnetic resonance or histology. ConclusionsWe provide the first experimental evidence of the deleterious effect of acute LAI on atrial structural remodeling, characterized by early LA dilation, dysfunction, and fibrosis, and early occurrence of ischemic MR.

Dynamic Edematous Response of the Human Heart to Myocardial Infarction: Implications for Assessing Myocardial Area at Risk and Salvage.

Clinical protocols aimed to characterize the post-myocardial infarction (MI) heart by cardiac magnetic resonance (CMR) need to be standardized to take account of dynamic biological phenomena evolving early after the index ischemic event. Here, we evaluated the time course of edema reaction in patients with ST-segment-elevation MI by CMR and assessed its implications for myocardium-at-risk (MaR) quantification both in patients and in a large-animal model. A total of 16 patients with anterior ST-segment-elevation MI successfully treated by primary angioplasty and 16 matched controls were prospectively recruited. In total, 94 clinical CMR examinations were performed: patients with ST-segment-elevation MI were serially scanned (within the first 3 hours after reperfusion and at 1, 4, 7, and 40 days), and controls were scanned only once. T2 relaxation time in the myocardium (T2 mapping) and the extent of edema on T2-weighted short-tau triple inversion-recovery (ie, CMR-MaR) were evaluated at all time points. In the experimental study, 20 pigs underwent 40-minute ischemia/reperfusion followed by serial CMR examinations at 120 minutes and 1, 4, and 7 days after reperfusion. Reference MaR was assessed by contrast-multidetector computed tomography during the index coronary occlusion. Generalized linear mixed models were used to take account of repeated measurements. In humans, T2 relaxation time in the ischemic myocardium declines significantly from early after reperfusion to 24 hours, and then increases up to day 4, reaching a plateau from which it decreases from day 7. Consequently, edema extent measured by T2-weighted short-tau triple inversion-recovery (CMR-MaR) varied with the timing of the CMR examination. These findings were confirmed in the experimental model by showing that only CMR-MaR values for day 4 and day 7 postreperfusion, coinciding with the deferred edema wave, were similar to values measured by reference contrast-multidetector computed tomography. Post-MI edema in patients follows a bimodal pattern that affects CMR estimates of MaR. Dynamic changes in post-ST-segment-elevation MI edema highlight the need for standardization of CMR timing to retrospectively delineate MaR and quantify myocardial salvage. According to the present clinical and experimental data, a time window between days 4 and 7 post-MI seems a good compromise solution for standardization. Further studies are needed to study the effect of other factors on these variables.

Effect of Ischemia Duration and Protective Interventions on the Temporal Dynamics of Tissue Composition After Myocardial Infarction.

The impact of cardioprotective strategies and ischemia duration on postischemia/reperfusion (I/R) myocardial tissue composition (edema, myocardium at risk, infarct size, salvage, intramyocardial hemorrhage, and microvascular obstruction) is not well understood. To study the effect of ischemia duration and protective interventions on the temporal dynamics of myocardial tissue composition in a translational animal model of I/R by the use of state-of-the-art imaging technology. Four 5-pig groups underwent different I/R protocols: 40-minute I/R (prolonged ischemia, controls), 20-minute I/R (short-duration ischemia), prolonged ischemia preceded by preconditioning, or prolonged ischemia followed by postconditioning. Serial cardiac magnetic resonance (CMR)-based tissue characterization was done in all pigs at baseline and at 120 minutes, day 1, day 4, and day 7 after I/R. Reference myocardium at risk was assessed by multidetector computed tomography during the index coronary occlusion. After the final CMR, hearts were excised and processed for water content quantification and histology. Five additional healthy pigs were euthanized after baseline CMR as reference. Edema formation followed a bimodal pattern in all 40-minute I/R pigs, regardless of cardioprotective strategy and the degree of intramyocardial hemorrhage or microvascular obstruction. The hyperacute edematous wave was ameliorated only in pigs showing cardioprotection (ie, those undergoing short-duration ischemia or preconditioning). In all groups, CMR-measured edema was barely detectable at 24 hours postreperfusion. The deferred healing-related edematous wave was blunted or absent in pigs undergoing preconditioning or short-duration ischemia, respectively. CMR-measured infarct size declined progressively after reperfusion in all groups. CMR-measured myocardial salvage, and the extent of intramyocardial hemorrhage and microvascular obstruction varied dramatically according to CMR timing, ischemia duration, and cardioprotective strategy. Cardioprotective therapies, duration of index ischemia, and the interplay between these greatly influence temporal dynamics and extent of tissue composition changes after I/R. Consequently, imaging techniques and protocols for assessing edema, myocardium at risk, infarct size, salvage, intramyocardial hemorrhage, and microvascular obstruction should be standardized accordingly.

P567Early diagnosis of anthracycline induced cardiotoxicity in a swine model by serial multiparametric cardiac magnetic resonance

P567Early diagnosis of anthracycline induced cardiotoxicity in a swine model by serial multiparametric cardiac magnetic resonance

Association of Concentric Left Ventricular Hypertrophy With Subsequent Change in Left Ventricular End-Diastolic Volume: The Dallas Heart Study.

In the conventional paradigm of the progression of left ventricular hypertrophy, a thick-walled left ventricle (LV) ultimately transitions to a dilated cardiomyopathy. There are scant data in humans demonstrating whether this transition occurs commonly without an interval myocardial infarction. Participants (n=1282) from the Dallas Heart Study underwent serial cardiac magnetic resonance ≈7 years apart. Those with interval cardiovascular events and a dilated LV (increased LV end-diastolic volume [EDV] indexed to body surface area) at baseline were excluded. Multivariable linear regression models tested the association of concentric hypertrophy (increased LV mass and LV mass/volume0.67) with change in LVEDV. The study cohort had a median age of 44 years, 57% women, 43% black, and 11% (n=142) baseline concentric hypertrophy. The change in LVEDV in those with versus without concentric hypertrophy was 1 mL (-9 to 12) versus -2 mL (-11 to 7), respectively, P<0.01. In multivariable linear regression models, concentric hypertrophy was associated with larger follow-up LVEDV (P≤0.01). The progression to a dilated LV was uncommon (2%, n=25). In the absence of interval myocardial infarction, concentric hypertrophy was associated with a small, but significantly greater, increase in LVEDV after 7-year follow-up. However, the degree of LV enlargement was minimal, and few participants developed a dilated LV. These data suggest that if concentric hypertrophy does progress to a dilated cardiomyopathy, such a transition would occur over a much longer timeframe (eg, decades) and perhaps less common than previously thought. URL: http://www.clinicaltrials.gov. Unique identifier: NCT00344903.

Longitudinal Changes in Segmental Aortic Stiffness Determined by Cardiac Magnetic Resonance in Children and Young Adults With Connective Tissue Disorders (the Marfan, Loeys-Dietz, and Ehlers-Danlos Syndromes, and Nonspecific Connective Tissue Disorders)

Aortic stiffness measured by cardiac magnetic resonance (CMR) in connective tissue disorder (CTD) patients has been previously shown to be abnormal and to be associated with adverse aortic outcomes. The rate of increase in aortic stiffness with normal aging has been previously described. However, longitudinal changes in aortic stiffness have not been characterized in CTD patients. We examined longitudinal changes in CMR-derived aortic stiffness in children and young adults with CTDs. A retrospective analysis of 50 children and young adults (median age, 20 years; range, 0.2 to 49; 40% < 18 years old) with a CTD, and with at least 2 CMR examinations (total 152 examinations) over a median duration of 3.9 (1 to 13.2) years was performed. Aortic stiffness measures (strain, distensibility, and β stiffness index) were calculated on each examination at the aortic root (AoR), ascending aorta, and descending aorta. Longitudinal changes in parameters were analyzed using linear mixed-effects models. Aortic strain and distensibility decreased with age, whereas the β stiffness index increased at all aortic segments. The average rates of decline in distensibility (x10-3 mm Hg-1 per 10-year increase in age) were 0.7, 1.3, and 1 at the AoR, ascending aorta, and descending aorta, respectively. The rates of decline in distensibility were not associated with the rates of AoR dilation or surgical AoR replacement. In conclusion, on serial CMR measurements in children and young adults with CTDs, aortic stiffness progressively increased with age, with rates of change only slightly higher than those previously reported in healthy adults.

012 Longitudinal cardiac magnetic resonance assessment of diffuse and replacement myocardial fibrosis in aortic stenosis

Objective To investigate whether cardiac magnetic resonance (CMR) can assess the progression and regression of myocardial fibrosis in patients with aortic stenosis (AS). Methods Sixty-three patients with aortic stenosis were followed up for 2 years with serial CMR and echocardiography: 28 patients (63±13 years, 68% male, 50% asymptomatic severe AS) did not undergo intervention ( natural history cohort ) and 35 patients (67±8 years, 73% male, 83% symptomatic severe AS) underwent aortic valve replacement (AVR) within the first year ( AVR cohort ). Replacement and diffuse myocardial fibrosis were assessed using the late gadolinium enhancement (LGE) and T1 mapping techniques respectively. Annualised change was calculated for all measures. Results In the natural history cohort, left ventricular mass index (LVMi) increased over time (6%±1%, p The AVR cohort displayed a fall in LVMi following surgery (−15%±2%, p Conclusion Changes in diffuse fibrosis can be tracked using iECV and increase with time in patients with AS alongside LV mass and replacement fibrosis. Following AVR there is a fall in LV mass driven predominantly by regression of cellular hypertrophy with more gradual reduction in diffuse fibrosis burden but no change in replacement fibrosis. Mid-wall LGE is present on baseline scan (white arrow) and new areas are seen on 1 year scan (red arrows). Following AVR there is no change in mid-wall LGE (white arrows). Annualised change in imaging measures is presented below in the natural history (black) and AVR (red) groups.

Microvascular leakage in acute myocardial infarction: characterization by histology, biochemistry, and magnetic resonance imaging.

Cardiac microvascular obstruction (MVO) after ischemia-reperfusion (I/R) has been well studied, but microvascular leakage (MVL) remains largely unexplored. We characterized MVL in the mouse I/R model by histology, biochemistry, and cardiac magnetic resonance (CMR) imaging. I/R was induced surgically in mice. MVL was determined by administrating the microvascular permeability tracer Evans blue (EB) and/or gadolinium-diethylenetriaminepentaacetic acid contrast. The size of MVL, infarction, and MVO in the heart was quantified histologically. Myocardial EB was extracted and quantified chromatographically. Serial CMR images were acquired from euthanized mice to determine late gadolinium enhancement (LGE) for comparison with MVL quantified by histology. I/R resulted in MVL with its severity dependent on the ischemic duration and reaching its maximum at 24-48 h after reperfusion. The size of MVL correlated with the degree of left ventricular dilatation and reduction in ejection fraction. Within the risk zone, the area of MVL (75 ± 2%) was greater than that of infarct (47 ± 4%, P < 0.01) or MVO (36 ± 4%, P < 0.01). Contour analysis of paired CMR-LGE by CMR and histological MVL images revealed a high degree of spatial colocalization (r = 0.959, P < 0.0001). These data indicate that microvascular barrier function is damaged after I/R leading to MVL. Histological and biochemical means are able to characterize MVL by size and severity while CMR-LGE is a potential diagnostic tool for MVL. The size of ischemic myocardium exhibiting MVL was greater than that of infarction and MVO, implying a role of MVL in postinfarct pathophysiology.NEW & NOTEWORTHY We characterized, for the first time, the features of microvascular leakage (MVL) as a consequence of reperfused myocardial infarction. The size of ischemic myocardium exhibiting MVL was significantly greater than that of infarction or no reflow. We made a proof-of-concept finding on the diagnostic potential of MVL by cardiac magnetic resonance imaging.

Longitudinal changes in adolescents with TOF: implications for care

We sought to identify predictors of change in right ventricular function and exercise capacity in adolescents following repair for tetralogy of Fallot. We performed a longitudinal study with serial cardiac magnetic resonance imaging and/or exercise stress tests. Patients with interim intervention on the pulmonary valve were excluded. Paired t-test was used to detect longitudinal changes and multivariable regression models were built to identify predictors of change. Initial and follow up magnetic resonance and exercise stress test studies were available for 65 and 63 subjects, respectively. Age at initial testing was 11.7 ± 2.7 years. Average follow up time was 4.5 ± 1.8 (magnetic resonance) and 4.0 ± 1.6 (exercise test) years. There was a significant increase in right ventricular end diastolic and systolic volume (119 ± 34 to 128 ± 35 ml/m2, P = 0.006; 49 ± 20 to 56 ± 23 ml/m2, P = 0.001, respectively), and a decrease in right ventricular ejection fraction (60 ± 7 to 56 ± 8%, P = 0.001), with no significant change in pulmonary regurgitant fraction or right ventricular cardiac index. Predictors of right ventricular dilation over time included: time elapsed from surgical repair, severity of pulmonary insufficiency and right ventricular dilation at the initial magnetic resonance imaging. Of those, time elapsed from surgical repair had the most significant effect. There was no change in exercise capacity. In the adolescent with tetralogy of Fallot, longer time from surgery, more pulmonary insufficiency and greater right ventricular dilation at initial magnetic resonance imaging are associated with progressive right ventricular dilation. These results suggest early monitoring with magnetic resonance imaging might identify those at highest risk for progressive disease.

Characterization of the Changes in Cardiac Structure and Function in Mice Treated With Anthracyclines Using Serial Cardiac Magnetic Resonance Imaging.

Anthracyclines are cardiotoxic; however, there are limited data characterizing the serial changes in cardiac structure and function after anthracyclines. The aim of this study was to use cardiac magnetic resonance to characterize anthracycline-induced cardiotoxicity in mice. This was a longitudinal cardiac magnetic resonance and histological study of 45 wild-type male mice randomized to doxorubicin (n=30, 5 mg/kg of doxorubicin/week for 5 weeks) or placebo (n=15). A cardiac magnetic resonance was performed at baseline and at 5, 10, and 20 weeks after randomization. Measures of primary interest included left ventricular ejection fraction, myocardial edema (multiecho short-axis spin-echo acquisition), and myocardial fibrosis (Look-Locker gradient echo). In doxorubicin-treated mice versus placebo, there was an increase in myocardial edema at 5 weeks (T2 values of 32±4 versus 21±3 ms; P<0.05), followed by a reduction in left ventricular ejection fraction (54±6 versus 63±5%; P<0.05) and an increase in myocardial fibrosis (extracellular volume of 0.34±0.03 versus 0.27±0.03; P<0.05) at 10 weeks. There was a strong association between the early (5 weeks) increase in edema and the subacute (10 weeks) increase in fibrosis (r=0.90; P<0.001). Both the increase in edema and fibrosis predicted the late doxorubicin-induced mortality in mice (P<0.001). Our data suggest that, in mice, anthracycline-induced cardiotoxicity is associated with an early increase in cardiac edema and a subsequent increase in myocardial fibrosis. The early increase in edema and subacute increase in fibrosis are strongly linked and are both predictive of late mortality.

Adverse diastolic remodeling after reperfused ST-elevation myocardial infarction: An important prognostic indicator

We sought to determine the relationship of adverse diastolic remodeling (ie, worsening diastolic or persistent restrictive filling) with infarct scar characteristics, and to evaluate its prognostic value after ST-segment elevation myocardial infarction (STEMI). Severe diastolic dysfunction (restrictive filling) has known prognostic value post STEMI. However, ongoing left ventricular (LV) remodeling post STEMI may alter diastolic function even if less severe. There were 218 prospectively recruited STEMI patients with serial echocardiograms (transthoracic echocardiography) and cardiac magnetic resonance imaging (CMR) performed, at a median of 4 days (early) and 55 days (follow-up). LV ejection fraction and infarct characteristics were assessed by CMR, and comprehensive diastolic function assessment including a diastolic grade was evaluated on transthoracic echocardiography. 'Adverse diastolic remodeling' occurred if diastolic function grade either worsened (≥1 grade) between early and follow-up imaging, or remained as persistent restrictive filling at follow-up. Follow-up infarct scar size (IS) predicted adverse diastolic remodeling (area under the curve 0.86) and persistent restrictive filling (area under the curve 0.89). The primary endpoint of major adverse cardiovascular events (MACE) occurred in 48 patients during follow-up (mean, 710±79 days). Kaplan-Meier analysis showed that adverse diastolic remodeling (n=50) and persistent restrictive filling alone (n=33) were significant predictors of MACE (both P<.001). Multivariate Cox analysis, when adjusted for TIMI risk score and CMR IS, microvascular obstruction, and LV ejection fraction, showed adverse diastolic remodeling (HR 3.79, P<.001) was an independent predictor of MACE, as was persistent restrictive filling alone (HR 2.61, P=.019). Larger IS is associated with adverse diastolic remodeling. Following STEMI, adverse diastolic remodeling is a powerful prognostic marker, and identifies a larger group of 'at-risk' patients, than does persistent restrictive filling alone.

Overexpression of A kinase interacting protein 1 attenuates myocardial ischaemia/reperfusion injury but does not influence heart failure development.

A kinase interacting protein 1 (AKIP1) stimulates physiological growth in cultured cardiomyocytes and attenuates ischaemia/reperfusion (I/R) injury in ex vivo perfused hearts. We aimed to determine whether AKIP1 modulates the cardiac response to acute and chronic cardiac stresses in vivo. Transgenic mice with cardiac-specific overexpression of AKIP1 (AKIP1-TG) were created. AKIP1-TG mice and their wild-type (WT) littermates displayed similar cardiac structure and function. Likewise, cardiac remodelling in response to transverse aortic constriction or permanent coronary artery ligation was identical in AKIP1-TG and WT littermates, as evidenced by serial cardiac magnetic resonance imaging and pressure-volume loop analysis. Histological indices of remodelling, including cardiomyocyte cross-sectional diameter, capillary density, and left ventricular fibrosis were also similar in AKIP1-TG mice and WT littermates. When subjected to 45 min of ischaemia followed by 24 h of reperfusion, AKIP1-TG mice displayed a significant two-fold reduction in myocardial infarct size and reductions in cardiac apoptosis. In contrast to previous reports, AKIP1 did not co-immunoprecipitate with or regulate the activity of the signalling molecules NF-κB, protein kinase A, or AKT. AKIP1 was, however, enriched in cardiac mitochondria and co-immunoprecipitated with a key component of the mitochondrial permeability transition (MPT) pore, ATP synthase. Finally, mitochondria isolated from AKIP1-TG hearts displayed markedly reduced calcium-induced swelling, indicative of reduced MPT pore formation. In contrast to in vitro studies, AKIP1 overexpression does not influence cardiac remodelling in response to chronic cardiac stress. AKIP1 does, however, reduce myocardial I/R injury through stabilization of the MPT pore. These findings suggest that AKIP1 deserves further investigation as a putative treatment target for cardioprotection from I/R injury during acute myocardial infarction.