Myocardial extracellular volume fraction quantified by cardiovascular magnetic resonance is increased in diabetes and associated with mortality and incident heart failure admission

Wong, Timothy C.; Piehler, Kayla; Kang, Ian A.; Kadakkal, Ajay; Kellman, Peter; Schwartzman, David; Mulukutla, Suresh; Simon, Marc A.; Shroff, Sanjeev G.; Kuller, Lewis H.; Schelbert, Erik B.

doi:10.1093/eurheartj/eht193

Cited by 332 publications

(264 citation statements)

References 36 publications

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“…The ECV values in themselves are comparable with those reported in other heart conditions, such as post-myocarditis, cardiomyopathies, diabetic heart and thus it is unlikely that ECV would have any quantitative value in differentiating the post-takotsubo heart from other conditions 38,39 . The real significance of our findings is the striking lack of return to a normal myocardial structure in a condition considered until recently as "a fully reversible form of acute cardiomyopathy".…”

Section: Importance and Extent Of Systolic Diastolic And Extracellulsupporting

confidence: 74%

Alterations in Cardiac Deformation, Timing of Contraction and Relaxation, and Early Myocardial Fibrosis Accompany the Apparent Recovery of Acute Stress-Induced (Takotsubo) Cardiomyopathy: An End to the Concept of Transience

Schwarz

Ahearn

Srinivasan

et al. 2017

Journal of the American Society of Echocardiography

108

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Background: Takotsubo syndrome is an increasingly recognized cause of chest pain and occasionally of cardiogenic shock. Despite rapid improvement of the Left Ventricular Ejection Fraction (LV EF), recent registry data raises concerns about long term prognosis. We hypothesized that restoration of normal EF after acute tako-tsubo is not equivalent to full functional recovery. Methods: We prospectively recruited 52 takotsubo patients [according to the Mayo criteria plus cardiac magnetic resonance imaging (CMR) to exclude myocardial infarction] and 44 healthy controls of the same age, gender and cardiovascular co-morbidity distribution. We focused the investigation on takotsubo patients presenting with ST-elevation type ECG or malignant arrhythmias and with LV apical ballooning variant and examined a 4 months recovery end-point. Patients underwent Echocardiography assessment of LV myocardial deformation (Global longitudinal, radial and circumferential strain, LV twist, torsion, untwist, time to peak twist and untwist) and assessment of LV myocardial structure by pre and post contrast-enhanced CMR by T1 mapping acutely and at 4 months follow-up. Controls had a single time-point investigation. Data were analyzed using paired or unpaired tests, as appropriate for their distribution and corrected for multiple comparisons. Results: The patients' mean age was 66 years (range 28-87) and 92% were women. All abnormal echocardiographic indices observed acutely in takotsubo patients improved (but not necessarily normalized) at followup. Significant mechano-temporal alterations characterizing both systole (global longitudinal strain, apical circumferential strain, both p<0.01; left ventricular twist, twist rate and torsion, all p<0.0001) and diastole (untwist rate and time to peak untwisting, all p<0.001) persisted at 4 months follow-up when compared with controls, despite normalization of LV ejection fraction and volumes. Whilst native T1 (which demonstrates edema) normalized at 4 months follow-up only in segments contracting normally during the acute phase [T1=1180± 40.6ms (normally contracting, p=0.2 vs control values of 1189±16 ms) and 1208± 60.3 ms (dysfunctional segments, p<0.05 vs control)], the extracellular volume fraction (ECV, which demonstrates diffuse fibrosis) remained significantly abnormal in all LV segments (whether normally contracting, 0.328±0.043, p<0.001 or ballooning during acute presentation, 0.320±0.044, p<0.001, both vs control values of 0.273±0.045). Conclusion: In patients with the most clinically severe spectrum of takotsubo cardiomyopathy, regional LV systolic and diastolic deformation abnormalities persist beyond the acute event, despite normalization of global LV EF and size. In addition, although myocardial edema partly subsides, a process of global microscopic fibrosis develops in its place, detected as early as 4 months.Suggested Reviewers:Opposed Reviewers: 1 24 th March, 2017 Dear Dr Pearlman, Thank you once again for your comments and those of the associate editors. I think it i...

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Section: Importance and Extent Of Systolic Diastolic And Extracellulsupporting

confidence: 74%

Alterations in Cardiac Deformation, Timing of Contraction and Relaxation, and Early Myocardial Fibrosis Accompany the Apparent Recovery of Acute Stress-Induced (Takotsubo) Cardiomyopathy: An End to the Concept of Transience

Schwarz

Ahearn

Srinivasan

et al. 2017

Journal of the American Society of Echocardiography

108

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“…Alterations of the structural properties and intercellular coupling of the myocardium may have occurred with diabetes,52, 68, 69 weakening the electrotonic interaction between myocytes, which acts as a mechanism of suppression of repolarization variability in situ 54, 70. Thus, intervening structural remodeling may have cooperated with reduced Kv currents in promoting the repolarization heterogeneity found in the diabetic heart.…”

Section: Discussionmentioning

confidence: 99%

Reduction in Kv Current Enhances the Temporal Dispersion of the Action Potential in Diabetic Myocytes: Insights From a Novel Repolarization Algorithm

Meo

Meste

Signore

et al. 2016

JAHA

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BackgroundDiabetes is associated with prolongation of the QT interval of the electrocardiogram and enhanced dispersion of ventricular repolarization, factors that, together with atherosclerosis and myocardial ischemia, may promote the occurrence of electrical disorders. Thus, we tested the possibility that alterations in transmembrane ionic currents reduce the repolarization reserve of myocytes, leading to action potential (AP) prolongation and enhanced beat‐to‐beat variability of repolarization.Methods and ResultsDiabetes was induced in mice with streptozotocin (STZ), and effects of hyperglycemia on electrical properties of whole heart and myocytes were studied with respect to an untreated control group (Ctrl) using electrocardiographic recordings in vivo, ex vivo perfused hearts, and single‐cell patch‐clamp analysis. Additionally, a newly developed algorithm was introduced to obtain detailed information of the impact of high glucose on AP profile. Compared to Ctrl, hyperglycemia in STZ‐treated animals was coupled with prolongation of the QT interval, enhanced temporal dispersion of electrical recovery, and susceptibility to ventricular arrhythmias, defects observed, in part, in the Akita mutant mouse model of type I diabetes. AP was prolonged and beat‐to‐beat variability of repolarization was enhanced in diabetic myocytes, with respect to Ctrl cells. Density of Kv K+ and L‐type Ca2+ currents were decreased in STZ myocytes, in comparison to cells from normoglycemic mice. Pharmacological reduction of Kv currents in Ctrl cells lengthened AP duration and increased temporal dispersion of repolarization, reiterating features identified in diabetic myocytes.ConclusionsReductions in the repolarizing K+ currents may contribute to electrical disturbances of the diabetic heart.

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“…ECV quantification by T1 mapping has significant prognostic implications. Wong et al [40] have demonstrated an association between myocardial extracellular expansion and adverse clinical outcomes using ECV. T1 mapping techniques have another advantage of detecting diffuse fibrosis at early stages of the disease.…”

Section: The Role Of T1 Mapping For Detection Of Diffuse Myocardial Fmentioning

confidence: 99%

Cardiovascular magnetic resonance imaging in hypertrophic cardiomyopathy: Current state of the art

2016

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Myocardial extracellular volume fraction quantified by cardiovascular magnetic resonance is increased in diabetes and associated with mortality and incident heart failure admission

Cited by 332 publications

References 36 publications

Alterations in Cardiac Deformation, Timing of Contraction and Relaxation, and Early Myocardial Fibrosis Accompany the Apparent Recovery of Acute Stress-Induced (Takotsubo) Cardiomyopathy: An End to the Concept of Transience

Alterations in Cardiac Deformation, Timing of Contraction and Relaxation, and Early Myocardial Fibrosis Accompany the Apparent Recovery of Acute Stress-Induced (Takotsubo) Cardiomyopathy: An End to the Concept of Transience

Reduction in Kv Current Enhances the Temporal Dispersion of the Action Potential in Diabetic Myocytes: Insights From a Novel Repolarization Algorithm

Cardiovascular magnetic resonance imaging in hypertrophic cardiomyopathy: Current state of the art

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