The effect of dapagliflozin on ventricular arrhythmias, cardiac arrest, or sudden death in people with heart failure: a tick in another box for sodium-glucose cotransporter 2 inhibitors

Author(s):  
Theocharis Koufakis ◽  
George Giannakoulas ◽  
Pantelis Zebekakis ◽  
Kalliopi Kotsa
Author(s):  
Jae Hyung Cho ◽  
Rui Zhang ◽  
Stephan Aynaszyan ◽  
Kevin Holm ◽  
Joshua I. Goldhaber ◽  
...  

Circulation ◽  
2000 ◽  
Vol 101 (1) ◽  
pp. 40-46 ◽  
Author(s):  
John R. Teerlink ◽  
Muhammad Jalaluddin ◽  
Susan Anderson ◽  
Marrick L. Kukin ◽  
Eric J. Eichhorn ◽  
...  

1988 ◽  
Vol 116 (6) ◽  
pp. 1447-1454 ◽  
Author(s):  
William G Stevenson ◽  
Lynne W Stevenson ◽  
James Weiss ◽  
Jan H Tillisch

1999 ◽  
Vol 277 (1) ◽  
pp. H80-H91 ◽  
Author(s):  
H. Bradley Nuss ◽  
Stefan Kääb ◽  
David A. Kass ◽  
Gordon F. Tomaselli ◽  
Eduardo Marbán

The high incidence of sudden death in heart failure may reflect an increased propensity to abnormal repolarization and long Q-T interval-related arrhythmias. If so, cells from failing hearts would logically be expected to exhibit a heightened susceptibility to early afterdepolarizations (EAD). We found that midmyocardial ventricular cells isolated from dogs with pacing-induced heart failure exhibited an increased action potential duration and many more EAD than cells from nonpaced controls; this was the case both under basal conditions ( P < 0.01) and after lowering external K+concentration ([K+]o) to 2 mM and exposing cells to cesium (3 mM; P < 0.05). An unexpected finding was the occurrence of spontaneous depolarizations (SD, >5 mV) from the resting potential that were not coupled to prior action potentials. These SD were observed in 20% of failing cells ( n = 5 of 25) under basal ionic conditions but in none of the normal cells ( n = 0 of 27, P < 0.05). The net inward current that underlies SD is not triggered by Ca2+ oscillations and thus differs fundamentally from the currents that underlie delayed afterdepolarizations. We conclude that cardiomyopathic canine ventricular cells are intrinsically predisposed to EAD and SD. Because EAD have been linked to the pathogenesis of torsade de pointes, our results support the hypothesis that sudden death in heart failure often arises from abnormalities of repolarization. The frequent occurrence of SD points to a novel cellular mechanism for abnormal automaticity in heart failure.


Circulation ◽  
2000 ◽  
Vol 101 (25) ◽  
pp. 2975-2980 ◽  
Author(s):  
Tobias Opthof ◽  
Ruben Coronel ◽  
Han M. E. Rademaker ◽  
Jessica T. Vermeulen ◽  
Francien J. G. Wilms-Schopman ◽  
...  

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
M Mirabel ◽  
P Karapetiantz ◽  
E Marijon ◽  
C Le Beller ◽  
Z Reda Al-Sayed ◽  
...  

Abstract Background Immune checkpoint inhibitors (ICI) have significantly improved the prognosis of many advanced cancers, and may be given in non-metastatic cancer in the near future. ICI have recently been reported to induce fulminant cardiotoxic effects such as myocarditis, responsible for ∼50% mortality rates. Objective To estimate the risk of sudden death (SD) and ventricular arrhythmias in patients receiving ICI using the World Health Organization individual case safety report (ICSR) database, Vigibase (WHO international pharmacovigilance database). Methods The system organ class MEDRA was used to identify cases as ICSR with the terms sudden death, sudden cardiac death, cardiac arrest, ventricular fibrillation, ventricular tachycardia, ventricular arrhythmia and torsades de pointes (named as SD events) from Nov 1967 to Nov 2019. We used the ATC code L01 which regroups 219 antineoplastic agents including ICI avelumab (anti-PDL1), ipilimumab (anti CTLA4), nivolumab (anti-PD1) and pembrolizumab (anti-PD1). A disproportionality analysis was performed to estimate of relative Odds Ratio (ROR). Signals were considered significant when the lower boundary of the 99.97% confidence interval (ROR0.25) was ≥1. Results We found that avelumab was significantly associated with SD events (ROR0.25=1.7). This overreporting was not observed for other ICIs. Avelumab was associated with 12 cases of cardiac arrest (n=11) or sudden death (n=1), which were reported since 2017 as the drug became available. There were however no signals regarding other terms including ventricular arrhythmias. Conclusions In spite of the potential severity of ICI-myocarditis, ICI do not appear as associated with the occurrence of sudden death or life-threatening arrhythmias, with the exception of avelumab (anti-PDL1), one of the latest developed ICI, indicated in metastatic Merkel cell carcinoma and advanced renal cell carcinoma. Further attention is warranted to confirm this signal that may vary among ICI therapies. Funding Acknowledgement Type of funding source: None


Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Zachary K Wegermann ◽  
Shuang Li ◽  
Nathaniel Smilowitz ◽  
Hani Jneid ◽  
bryan H wilson ◽  
...  

Introduction: Stable patients with STEMI and successful reperfusion may be considered for early discharge; however, little is known about the incidence of late ventricular tachycardia or fibrillation (VT/VF occurring at least 1 day after PCI) that may warrant further monitoring. Methods: We identified 162,822 STEMI patients treated with primary PCI and without VT/VF on the day of PCI in the NCDR Chest Pain-MI Registry from January 2015-December 2018. A low risk subgroup (n=96,188) was identified by excluding patients with prior MI, heart failure, systolic BP<90 mmHg, cardiogenic shock, cardiac arrest, re-infarction on the day of PCI, or ejection fraction<40%. The incidence and timing of VT/VF (any VT≥7 beats or VF) was determined in the overall and low risk cohorts. The association between late VT/VF and in-hospital mortality was evaluated using multivariable logistic regression. Results: Late VT/VF occurred in 2.6% of patients overall and 1.8% in the low risk cohort. In patients with late VT/VF, cardiac arrest occurred in 20.3% and 7.7% of the overall and low risk cohorts, respectively. Many late VT/VF events (37.0% overall, 24.4% low risk cohort) occurred ≥2 days after PCI. Patients with late VT/VF were older, more likely to be men, and have prior cardiovascular disease or risk factors than patients without VT/VF; they also had higher rates of post-PCI heart failure, cardiogenic shock, cardiac arrest, and stroke ( Figure ). The risk of death was higher for patients with vs. without VT/VF in both the overall (15.4% vs. 2.4%, adjusted OR [aOR] 6.40, 95% CI 5.63-7.29) and low risk cohorts (3.7% vs. 0.5%, aOR 8.74, 95% CI 6.53-11.70). Conclusions: Late VT/VF after STEMI was infrequent but often occurred ≥2 days post-PCI and was associated with an increased risk of death, even in the low risk cohort. Novel ways to monitor and rapidly treat late VT/VF may avoid prolonged hospitalization after STEMI.


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