Sustained Ventricular Tachycardia in a Patient with Thalassemia Major

Bayar, Nermin; Arslan, Şakir; Erkal, Zehra; Küçükseymen, Selçuk

doi:10.1111/anec.12085

Cited by 4 publications

(7 citation statements)

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“…While it has been well acknowledged that IO results in cardiomyopathy [ 1 , 2 , 3 ], it remains unclear whether IO may play a causal role in cardiac arrhythmogenesis and how mitochondrial dysfunction might be involved [ 4 , 5 ]. Clinical studies have reported the occurrence of atrial and ventricular tachyarrhythmias in patients with IO conditions [ 4 , 29 , 30 , 31 , 32 , 33 , 34 ]. For example, sustained ventricular tachycardia was observed in thalassemic patients with IO [ 29 ] Furthermore, Mancuso et al found low voltages in ECG recordings, T wave inversions, and supraventricular arrhythmias in thalassemic patients suffering from heart failure, while their age and sex matched controls had no ECG abnormalities [ 30 ].…”

Section: Discussionmentioning

confidence: 99%

“…Clinical studies have reported the occurrence of atrial and ventricular tachyarrhythmias in patients with IO conditions [ 4 , 29 , 30 , 31 , 32 , 33 , 34 ]. For example, sustained ventricular tachycardia was observed in thalassemic patients with IO [ 29 ] Furthermore, Mancuso et al found low voltages in ECG recordings, T wave inversions, and supraventricular arrhythmias in thalassemic patients suffering from heart failure, while their age and sex matched controls had no ECG abnormalities [ 30 ]. In addition, O in patients with sickle cell disease and hereditary hemochromatosis has been associated with the incidence of sudden cardiac death induced by severe arrhythmias [ 35 , 36 ].…”

Section: Discussionmentioning

confidence: 99%

“…Furthermore, a very recent report has proposed that the mitochondrial calcium uniporter (mCU) may also transport Fe into mitochondria, while Mfrn2 serves to regulate mCU transport [ 46 ]. Interestingly, some recent studies have suggested that mCUs are also involved in brain and heart mitochondrial dysfunction under IO conditions [ 7 , 29 ]. As summarized in our review article [ 47 ], Fe also exerts effects on ion channels in cardiomyocytes, e.g., L- and T-type Ca channels, K and Na channels.…”

Section: Discussionmentioning

confidence: 99%

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Iron Overload, Oxidative Stress and Calcium Mishandling in Cardiomyocytes: Role of the Mitochondrial Permeability Transition Pore

et al. 2020

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Iron (Fe) plays an essential role in many physiological processes. Hereditary hemochromatosis or frequent blood transfusions often cause iron overload (IO), which can lead to cardiomyopathy and arrhythmias; however, the underlying mechanism is not well defined. In the present study, we assess the hypothesis that IO promotes arrhythmias via reactive oxygen species (ROS) production, mitochondrial membrane potential (∆Ψm) depolarization, and disruption of cytosolic Ca dynamics. In ventricular myocytes isolated from wild type (WT) mice, both cytosolic and mitochondrial Fe levels were elevated following perfusion with the Fe3+/8-hydroxyquinoline (8-HQ) complex. IO promoted mitochondrial superoxide generation (measured using MitoSOX Red) and induced the depolarization of the ΔΨm (measured using tetramethylrhodamine methyl ester, TMRM) in a dose-dependent manner. IO significantly increased the rate of Ca wave (CaW) formation measured in isolated ventricular myocytes using Fluo-4. Furthermore, in ex-vivo Langendorff-perfused hearts, IO increased arrhythmia scores as evaluated by ECG recordings under programmed S1-S2 stimulation protocols. We also carried out similar experiments in cyclophilin D knockout (CypD KO) mice in which the mitochondrial permeability transition pore (mPTP) opening is impaired. While comparable cytosolic and mitochondrial Fe load, mitochondrial ROS production, and depolarization of the ∆Ψm were observed in ventricular myocytes isolated from both WT and CypD KO mice, the rate of CaW formation in isolated cells and the arrhythmia scores in ex-vivo hearts were significantly lower in CypD KO mice compared to those observed in WT mice under conditions of IO. The mPTP inhibitor cyclosporine A (CsA, 1 µM) also exhibited a protective effect. In conclusion, our results suggest that IO induces mitochondrial ROS generation and ∆Ψm depolarization, thus opening the mPTP, thereby promoting CaWs and cardiac arrhythmias. Conversely, the inhibition of mPTP ameliorates the proarrhythmic effects of IO.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Iron Overload, Oxidative Stress and Calcium Mishandling in Cardiomyocytes: Role of the Mitochondrial Permeability Transition Pore

et al. 2020

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“…These patients are lost due to cardiac failure and cardiac complications that occur as a result of iron deposition in the heart. In patients with thalassemia major, mortality rates reduced significantly due to intravenous and oral chelation therapy [3, 4]. Our patient could have reached the age of 23 because he had received regular chelation therapy.…”

Section: Discussionmentioning

confidence: 99%

“…Personalized treatment is usually applied in patients with VT due to iron overload. In literature, ICD implantation was performed in two similar cases [4, 8]. In our case, the implantation of DDD-ICD was coordinated with the decision of 3 electrophysiologists.…”

Section: Discussionmentioning

confidence: 99%

QT Prolongation and Associated Ventricular Tachycardia due to Cardiac Iron Load in a Patient with Thalassemia Major

Demirtaş

Sümbül

et al. 2019

Case Reports in Hematology

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We report the case of a 23-year-old male with thalassemia major who developed long QT and continuous ventricular tachycardia (VT). Electrocardiography, echocardiography, and cardiac magnetic resonance imaging (MRI) were used for diagnosis and risk stratification. VT causes and treatments are presented and discussed. Ventricular arrhythmia can be treated by normalizing QT interval with high-dose beta-blocker therapy. However, MRI-compatible internal cardiac defibrillator implantation was performed due to the high risk in this patient.

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Involvement of cytosolic and mitochondrial iron in iron overload cardiomyopathy: an update

et al. 2018

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Iron overload cardiomyopathy (IOC) is a major cause of death in patients with diseases associated with chronic anemia such as thalassemia or sickle cell disease after chronic blood transfusions. Associated with iron overload conditions, there is excess free iron that enters cardiomyocytes through both L- and T-type calcium channels thereby resulting in increased reactive oxygen species being generated via Haber-Weiss and Fenton reactions. It is thought that an increase in reactive oxygen species contributes to high morbidity and mortality rates. Recent studies have, however, suggested that it is iron overload in mitochondria that contributes to cellular oxidative stress, mitochondrial damage, cardiac arrhythmias, as well as the development of cardiomyopathy. Iron chelators, antioxidants, and/or calcium channel blockers have been demonstrated to prevent and ameliorate cardiac dysfunction in animal models as well as in patients suffering from cardiac iron overload. Hence, either a mono-therapy or combination therapies with any of the aforementioned agents may serve as a novel treatment in iron-overload patients in the near future. In the present article, we review the mechanisms of cytosolic and/or mitochondrial iron load in the heart which may contribute synergistically or independently to the development of iron-associated cardiomyopathy. We also review available as well as potential future novel treatments.

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Sustained Ventricular Tachycardia in a Patient with Thalassemia Major

Cited by 4 publications

References 7 publications

Iron Overload, Oxidative Stress and Calcium Mishandling in Cardiomyocytes: Role of the Mitochondrial Permeability Transition Pore

Iron Overload, Oxidative Stress and Calcium Mishandling in Cardiomyocytes: Role of the Mitochondrial Permeability Transition Pore

QT Prolongation and Associated Ventricular Tachycardia due to Cardiac Iron Load in a Patient with Thalassemia Major

Involvement of cytosolic and mitochondrial iron in iron overload cardiomyopathy: an update

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