Increased QT Interval Dispersion Predicts 15-Year Cardiovascular Mortality in Type 2 Diabetic Subjects

Giunti, Sara; Gruden, Gabriella; Fornengo, Paolo; Barutta, Federica; Amione, Cristina; Ghezzo, Giuseppe; Cavallo‐Perin, P.; Bruno, Graziella

doi:10.2337/dc11-1397

Cited by 30 publications

(21 citation statements)

References 16 publications

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“…Third, unlike APDs in isolated myocytes, the ECG from hearts in situ is under the influence of the autonomic nervous system. ECG changes in diabetic patients include QT prolongation and increased QT dispersion (5,21,40). QT dispersion is more strongly associated with cardiovascular events than is QT prolongation in diabetic patients.…”

Section: Discussionmentioning

confidence: 99%

Type 2 diabetes induces subendocardium-predominant reduction in transient outward K⁺ current with downregulation of Kv4.2 and KChIP2

Sato

Kobayashi

Kuno

et al. 2014

American Journal of Physiology-Heart and Circulatory Physiology

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In the present study, we examined if and how cardiac ion channels are modified by type 2 diabetes mellitus (T2DM). Subendocardial (Endo) myocytes and subepicardial (Epi) myocytes were isolated from left ventricles of Otsuka-Long-Evans-Tokushima Fatty rats (OLETF) rats, a rat model of T2DM, and Otsuka-Long-Evans-Tokushima (LETO) rats (nondiabetic control rats). Endo and Epi myocytes were used for whole cell patch-clamp recordings and for protein and mRNA analyses. Action potential durations in Endo and Epi myocytes were longer in OLETF rats than in LETO rats, and the difference was larger in Endo myocytes. Steady-state transient outward K ϩ current (Ito) density was reduced in Endo but not Epi myocytes of OLETF rats compared with LETO rats, although the contribution of the fast component of Ito recovery from inactivation was smaller in both Endo and Epi myocytes of OLETF rats than in LETO rats. Kv4.2 protein was reduced only in Endo myocytes in OLETF rats, although voltage-gated K ϩ channel-interacting protein 2 (KChIP2) protein levels in both Endo and Epi myocytes were lower in OLETF rats than in LETO rats. Corresponding regional differences in mRNA levels of KChIP2 and Kv4.2 were observed between OLETF and LETO rats. mRNA levels of Iroquois homeobox 5 in Endo myocytes were 53% higher in OLETF rats than in LETO rats. Densities of inward rectifier K ϩ current and L-type Ca 2ϩ current and mRNA levels of Kv4.3 and Kv1.4 were similar in OLETF and LETO rats. In conclusion, T2DM induces Endo-predominant prolongation of the action potential duration via a reduction of the fast component of (18). Diabetes is one of the diseases underlying heart failure with preserved left ventricular (LV) ejection fraction (2), and the prognosis of heart failure has been shown to be substantially worsened by diabetes. A number of studies in the past two decades have disclosed abnormalities in the microcirculation, mitochondria, and metabolism in diabetic hearts, as recently reviewed elsewhere (18). However, knowledge of electrical remodeling in the heart by type 2 DM (T2DM) is very limited. Most of the earlier studies used models of type 1 DM (T1DM; i.e., streptozotocin-induced and alloxan-induced diabetes) and showed that the action potential (AP) duration (APD) was prolonged and that the transient outward K ϩ current (I to ), L-type Ca 2ϩ current (I Ca,L ), and inward rectifier K ϩ current (I K1 ) were reduced in T1DM (31,38,45). However, it remains unclear whether T2DM induces the same electrical remodeling as that induced by T1DM. Hyperglycemia is a common feature in all animal models of diabetes, but plasma levels of insulin and lipids are different in T1DM and T2DM and also in models of T2DM (28,44). In addition, characteristics of LV pressurevolume relationship are different in T1DM and T2DM (25), indicating a possible difference in modifications of excitationcontraction coupling between the two types of DM.In the present study, we aimed to characterize the influence of T2DM on APD and ion currents in cardiomyocytes. We used Ots...

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Section: Discussionmentioning

confidence: 99%

Type 2 diabetes induces subendocardium-predominant reduction in transient outward K⁺ current with downregulation of Kv4.2 and KChIP2

Sato

Kobayashi

Kuno

et al. 2014

American Journal of Physiology-Heart and Circulatory Physiology

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“…In terms of geographical distribution, a total of 14 articles were from Europe (including two from Germany [9,10], four from Italy [11][12][13][14], one from the Netherlands [15], four from Sweden [16][17][18][19] and three from the UK [20][21][22]), 20 were from the Asia-Pacific region (including three from Australia [23][24][25], 10 from China [26][27][28][29][30][31][32][33][34][35], five from Japan [36][37][38][39][40] and two from Taiwan [41,42]), 13 were from North America (including one from Canada [43] and 12 from the USA [44][45][46][47][48][49][50][51][52][53][54][55]), two were from the Middle East (both conducted in Iran …”

Section: Methodsmentioning

confidence: 99%

Cardiovascular risk profiles in Type 2 diabetes and the impact of geographical setting

Smith-Palmer¹,

Boye

Pérez-Nieves

et al. 2014

Expert Review of Endocrinology & Metabolism

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Cardiovascular (CV) disease is a leading morbidity and mortality in Type 2 diabetes (T2DM). Previous studies have shown geographic differences in the prevalence of CV and renal diseases. A literature review of longitudinal ( ‡5 years) studies including ‡1000 T2DM patients and reporting CV endpoints was performed to compare risk profiles. Key differences between geographies included a relatively higher prevalence of microalbuminuria in East Asian relative to North American and European patients, which in turn is an important CV risk factor. Patients from East Asia also have a relatively higher incidence of stroke and lower incidence of coronary heart disease. Overall, there are differences in CV risk in T2DM patients between different regions and that long-term studies from Africa, the Middle East and Latin America are lacking.

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“…The clinical utility of the QT d as a predictor of cardiovascular mortality has been reported in various cardiovascular diseases, such as hypertension, chronic renal failure undergoing dialysis, type 2 diabetes, acute ST-elevation myocardial infarction undergoing primary percutaneous coronary intervention, metabolic syndrome, and obstructive sleep apnea syndrome, in previous studies (36)(37)(38)(39)(40)(41). Preeclampsia and other states that lead to abnormal uterine perfusion may change the ventricular repolarization before clinical symptoms occur (15).…”

Section: Discussionmentioning

confidence: 99%

P-Wave and QT Dispersion in Pregnant Women with Preeclampsia

Çakmak¹,

Çakmak²,

Özgen³

et al. 2016

JAREM

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Objective: Preeclampsia is an important cause of maternal and fetal mortality and morbidity worldwide. P-wave dispersion (P d ) and QT interval dispersion (QT d ) are direct measures of the nonhomogenity of atrial depolarization and ventricular repolarization, respectively, in electrocardiography (ECG). Recent studies have reported a significant role of prolonged P d and QT d in various cardiovascular diseases. Because the effect of acute pressure overload, which occurs in a preeclamptic setting, on the intra-and/or interatrial and ventricular conduction times remains unknown, we aimed to investigate the relation of P d and QT d with the presence and severity of preeclampsia.Methods: Forty-eight consecutive pregnant women with preeclampsia and 55 healthy, age-matched pregnant women were included in this retrospective study between January and September 2015. The pregnant women with preeclampsia were divided into two groups according to disease severity as follows: mild and severe preeclampsia. A 12-lead ECG was performed for all the pregnant women before cesarean section operation.Results: Compared with the healthy pregnant women, P d and QT d were significantly prolonged in patients with preeclampsia. Moreover, in the subgroups of preeclampsia, P d was significantly increased in the severe group. P d and QT d were directly related to systolic and diastolic blood pressure, which are well-known validated indicators for the severity of preeclampsia. Conclusion:Preeclampsia triggers an alteration of atrial depolarization and ventricular repolarization, which are evidenced by the prolongation of ECG parameters such as P d and QT d . ECG is a noninvasive, easy to use, and easily available diagnostic tool, which can be used in the assessment of atrial and ventricular electrical activity in pregnant women with preeclampsia.

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Increased QT Interval Dispersion Predicts 15-Year Cardiovascular Mortality in Type 2 Diabetic Subjects

Cited by 30 publications

References 16 publications

Type 2 diabetes induces subendocardium-predominant reduction in transient outward K⁺ current with downregulation of Kv4.2 and KChIP2

Type 2 diabetes induces subendocardium-predominant reduction in transient outward K⁺ current with downregulation of Kv4.2 and KChIP2

Cardiovascular risk profiles in Type 2 diabetes and the impact of geographical setting

P-Wave and QT Dispersion in Pregnant Women with Preeclampsia

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Increased QT Interval Dispersion Predicts 15-Year Cardiovascular Mortality in Type 2 Diabetic Subjects

Cited by 30 publications

References 16 publications

Type 2 diabetes induces subendocardium-predominant reduction in transient outward K+ current with downregulation of Kv4.2 and KChIP2

Type 2 diabetes induces subendocardium-predominant reduction in transient outward K+ current with downregulation of Kv4.2 and KChIP2

Cardiovascular risk profiles in Type 2 diabetes and the impact of geographical setting

P-Wave and QT Dispersion in Pregnant Women with Preeclampsia

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Type 2 diabetes induces subendocardium-predominant reduction in transient outward K⁺ current with downregulation of Kv4.2 and KChIP2

Type 2 diabetes induces subendocardium-predominant reduction in transient outward K⁺ current with downregulation of Kv4.2 and KChIP2