Cardiac arrhythmia considerations of hormone cancer therapies

Barber, Mary; Nguyen, Lee S.; Wassermann, Johanna; Spano, Jean‐Philippe; Funck‐Brentano, Christian; Salem, Joe‐Elie

doi:10.1093/cvr/cvz020

Cited by 49 publications

(44 citation statements)

References 109 publications

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“…The mechanism seems to be the decrease in the L-type calcium channel current and increase of several K currents including rapidly activating delayed rectifier current (I k r ), slowly activating delayed rectifier current (I ks ) and inward rectifier current Fig. 3 Comparison of the amount of QTc and Tpe/QT ratio variation between treatment groups: group A = degarelix in association with enzalutamide; group B = degarelix in monotherapy (I k1 ) [3,19,21,23,24]. After orchiectomy, the QT interval becomes longer than in healthy age-matched male subjects [19].…”

Section: Discussionmentioning

confidence: 99%

Evolution of Electrocardiographic Repolarization Parameters During Antiandrogen Therapy in Patients with Prostate Cancer and Hypogonadism

et al. 2020

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We assessed the effects of antiandrogen therapy on ECG parameters of ventricular repolarization related to arrhythmic risk in 35 patients aged 70.3 ± 7 years with advanced prostate cancer treated with degarelix associated with enzalutamide (group A, 26 patients) or degarelix monotherapy (group B, 9 patients). We analyzed Fridericia corrected Q-T interval (QTc), Q-T dispersion (QTd), J-Tpeak interval (JTp), mean and maximum Tpeak-Tend interval (Tpe) and Tpe/QT ratio, Tpeak-Tend dispersion (Tped), index of cardio-electrophysiological balance (iCEB) from ECG tracings, and occurrence of ventricular premature beats (VPB) recorded by Holter ECG, before initiation of medication (M0) and after 6 months of treatment (M1). The groups had similar demographics except for a higher prevalence of prior myocardial infarction in group B (p = 0.01). All patients had low serum testosterone at M1. Baseline QTc, QTd, maxTpe/QT, meanTpe, maxTpe, Tped values were higher in B compared to A. They had a significant prolongation at M1 only in A. 20 patients in A and 6 in B had a 10% prolongation or decrease of iCEB (p = 0.66). In 5 patients, VPB severity increased from non-complex to complex: 3 in A and 2 in B (p = 0.31), but no sustained ventricular arrhythmia was registered. In conclusion, after 6 months of treatment, patients with hypogonadism on degarelix associated with enzalutamide had significant prolongation of QTc, QTd, maxTpe, meanTpe/ QT, maxTpe/QT, Tped compared to patients on degarelix alone. The proportion of patients with 10% iCEB variation was similar between groups. There was no record of severe arrhythmias during the first 6 months of treatment.

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Section: Discussionmentioning

confidence: 99%

Evolution of Electrocardiographic Repolarization Parameters During Antiandrogen Therapy in Patients with Prostate Cancer and Hypogonadism

et al. 2020

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“…Strychnine Pesticide 10, 46 0.43 ± 0.02 (EC50) Cardiac arrest, bradycardia, ECG changes (Heiser et al, 1992;Wood et al, 2002;Ponraj et al, 2017) 3.8 mg/L ∼11 (Barbagallo et al, 2001;Yang et al, 2010;Salem et al, 2016;Barber et al, 2019) 6500 µg (65 kg human, 100 µg/kg i.v. )…”

Section: ∼3500-8000mentioning

confidence: 99%

A Bitter Taste in Your Heart

2020

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The human genome contains ∼29 bitter taste receptors (T2Rs), which are responsible for detecting thousands of bitter ligands, including toxic and aversive compounds. This sentinel function varies between individuals and is underpinned by naturally occurring T2R polymorphisms, which have also been associated with disease. Recent studies have reported the expression of T2Rs and their downstream signaling components within non-gustatory tissues, including the heart. Though the precise role of T2Rs in the heart remains unclear, evidence points toward a role in cardiac contractility and overall vascular tone. In this review, we summarize the extra-oral expression of T2Rs, focusing on evidence for expression in heart; we speculate on the range of potential ligands that may activate them; we define the possible signaling pathways they activate; and we argue that their discovery in heart predicts an, as yet, unappreciated cardiac physiology.

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“…In vitro, androgens lead to the shortening of ventricular action potential duration. The mechanism seems to be the decrease in the myocardial cells L-type calcium channel current and an increase of several K currents, such as rapidly activating delayed rectifier current (Ik r), slowly activating delayed rectifier current (Iks), and inward rectifier current (Ik1 ) [25][26][27]. After orchiectomy, the QT interval becomes longer than in healthy age-matched male subjects.…”

Section: Cardiovascular and Cardiometabolic Effects Of Testosteronementioning

confidence: 99%

Testosterone: Friend or foe for the cardiovascular system in men?

2020

Ann Clin Anal Med

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Epidemiological studies showed that cardiovascular diseases occur 7-10 years earlier in men than in women. One in two men and one in three women will have coronary artery disease events at the age of 40, and this observation is attributed to many factors, including differences in the steroidal hormonal status. In experimental trials, testosterone showed both beneficial and deleterious effects on the cardiovascular system. In addition, some trials found low levels of serum testosterone in men with coronary artery disease or heart failure and that patients with hypogonadism are at higher risk of cardiovascular diseases than patients with a normal serum level of testosterone. Clinical studies demonstrated cardiovascular deleterious effects of hypogonadism but no improvement with testosterone replacement therapy. It is unclear whether the differences in cardiovascular risk between men and women are due to the hormonal status or socio-cultural status.

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Cardiac arrhythmia considerations of hormone cancer therapies

Cited by 49 publications

References 109 publications

Evolution of Electrocardiographic Repolarization Parameters During Antiandrogen Therapy in Patients with Prostate Cancer and Hypogonadism

Evolution of Electrocardiographic Repolarization Parameters During Antiandrogen Therapy in Patients with Prostate Cancer and Hypogonadism

A Bitter Taste in Your Heart

Testosterone: Friend or foe for the cardiovascular system in men?

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