Digitalis Therapy and Risk of Recurrent Ventricular Tachyarrhythmias and ICD Therapies in Atrial Fibrillation and Heart Failure

Schupp, Tobias; Behnes, Michael; Weiß, Christel; Nienaber, Christoph; Reiser, Linda; Bollow, Armin; Taton, Gabriel; Reichelt, Thomas; Ellguth, Dominik; Engelke, Niko; Rusnak, Jonas; Weidner, Kathrin; Akin, Muharrem; Mashayekhi, Kambis; Borggrefe, Martin; Akın, İbrahim

doi:10.1159/000497271

Cited by 5 publications

(5 citation statements)

References 36 publications

(47 reference statements)

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“…We screened the full text of the remaining 83 studies and 62 articles were excluded due to the following reasons: (a) the full text of the article could not be located ( n = 4); (b) the data of the articles were insufficient or duplicated ( n = 5); (c) the articles were off topic ( n = 42); (d) the articles were reviews or commentaries ( n = 11). Finally, 21 studies [ 10 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 ] encompassing 44,761 ICD or CRT-D recipients were included in this systematic review and meta-analysis.…”

Section: Resultsmentioning

confidence: 99%

“…The baseline characteristics of the studies included in our analysis are presented in Table 1 . Among the 21 articles, 10 studies reported the appropriate shock rate [ 10 , 13 , 14 , 18 , 21 , 22 , 24 , 26 , 30 , 32 ], 2 studies [ 13 , 16 ] reported the time to the first appropriate shock, and 14 articles reported the mortality of ICD or CRT-D recipients [ 10 , 13 , 15 , 17 , 23 , 25 , 27 , 28 , 29 , 31 , 32 ]. Six of the included articles were prospective studies and fifteen were retrospective studies.…”

Section: Resultsmentioning

confidence: 99%

“…( A ) Forest plot of the association between digitalis and risk of appropriate shocks. ( B ) Forest plot assessing the time to first appropriate shock in ICD or CRT-D recipients administered digitalis [ 10 , 13 , 14 , 16 , 18 , 21 , 22 , 24 , 26 , 30 , 32 ].…”

Section: Figurementioning

confidence: 99%

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Effect of Digitalis on ICD or CRT-D Recipients: A Systematic Review and Meta-Analysis

Zhuo

Liu

et al. 2023

JCM

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Background: Digitalis has been widely utilized for heart failure therapy and several studies have demonstrated an association of digitalis and adverse outcome events in patients receiving implantable cardioverter defibrillators (ICDs) or cardiac resynchronization therapy defibrillators (CRT-Ds). Hence, we conducted this meta-analysis to assess the effect of digitalis on ICD or CRT-D recipients. Methods: We systematically retrieved relevant studies using the Cochrane Library, PubMed, and Embase database. A random effect model was used to pool the effect estimates (hazard ratios (HRs) and 95% confidence intervals (CIs)) when the studies were of high heterogeneity, otherwise a fixed effect model was used. Results: Twenty-one articles containing 44,761 ICD or CRT-D recipients were included. Digitalis was associated with an increased rate of appropriate shocks (HR = 1.65, 95% CI: 1.46–1.86, p < 0.001) and a shortened time to first appropriate shock (HR = 1.76, 95% CI: 1.17–2.65, p = 0.007) in ICD or CRT-D recipients. Furthermore, the all-cause mortality increased in ICD recipients with digitalis therapy (HR = 1.70, 95% CI: 1.34–2.16, p < 0.01), but the all-cause mortality was unchanged in CRT-D recipients (HR = 1.55, 95% CI: 0.92–2.60, p = 0.10) or patients who received ICD or CRT-D therapy (HR = 1.09, 95% CI: 0.80–1.48, p = 0.20). The sensitivity analyses confirmed the robustness of the results. Conclusion: ICD recipients with digitalis therapy may tend to have higher mortality rates, but digitalis may not be associated with the mortality rate of CRT-D recipients. Further studies are required to confirm the effects of digitalis on ICD or CRT-D recipients.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

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Effect of Digitalis on ICD or CRT-D Recipients: A Systematic Review and Meta-Analysis

Zhuo

Liu

et al. 2023

JCM

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“…Perhaps the use of digoxin heightens the risk of ventricular and atrial arrhythmias, which are known complications of digoxin. 24 While the DIG trial shows there is a reduction in death because of HF with chronic digoxin use, there was a reciprocal heightened risk of mortality attributable to arrhythmias. 15 In addition, myocardial ischemia increases the risk of fatal ventricular arrhythmias with digoxin therapy, 25 which may be problematic for patients with PAH as they are at risk for RV ischemia because of loss of right coronary artery perfusion during systole and capillary rarefaction.…”

Section: Discussionmentioning

confidence: 99%

Effect of Chronic Digoxin Use on Mortality and Heart Failure Hospitalization in Pulmonary Arterial Hypertension

Chang

Giorgio

Schmitz

et al. 2023

JAHA

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Background Digoxin acutely increases cardiac output in patients with pulmonary arterial hypertension (PAH) and right ventricular failure; however, the effects of chronic digoxin use in PAH are unclear. Methods and Results Data from the Minnesota Pulmonary Hypertension Repository were used. The primary analysis used likelihood of digoxin prescription. The primary end point was a composite of all‐cause mortality or heart failure (HF) hospitalization. Secondary end points included all‐cause mortality, HF hospitalization, and transplant‐free survival. Multivariable Cox proportional hazards analyses determined the hazard ratios (HR) and 95% CIs for the primary and secondary end points. Among 205 patients with PAH in the repository, 32.7% (n=67) were on digoxin. Digoxin was more often prescribed to patients with severe PAH and right ventricular failure. After propensity score‐matching, 49 patients were digoxin users, and 70 patients were nonusers; of these 31 (63.3%) in the digoxin group and 41 (58.6%) in nondigoxin group met the primary end point during a median follow‐up time of 2.1 (0.6–5.0) years. Digoxin users had a higher combined all‐cause mortality or HF hospitalization (HR, 1.82 [95% CI, 1.11–2.99]), all‐cause mortality (HR, 1.92 [95% CI, 1.06–3.49]), HF hospitalization (HR, 1.89 [95% CI, 1.07–3.35]), and worse transplant‐free survival (HR, 2.00 [95% CI, 1.12–3.58]) even after adjusting for patient characteristics and severity of PAH and right ventricular failure. Conclusions In this retrospective, nonrandomized cohort, digoxin treatment was associated with greater all‐cause mortality and HF hospitalization, even after multivariate correction. Future randomized controlled trials should assess the safety and efficacy of chronic digoxin use in PAH.

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“…Nowadays, MF detection primarily occurs via imaging or measuring the expression of related biomarkers; however, biomarkers that are directly associated with MF have not been identified (7,8). Diuretics, Digitalis and angiotensin-converting enzyme inhibitors are used to delay chronic HF in clinical settings, but display side effects and are not suitable for long-term treatment (9,10). Therefore, the identification of novel drugs and therapeutic targets to delay MF and prevent HF is important.…”

Section: Introductionmentioning

confidence: 99%

Matrix metalloproteinase 3 regulates angiotensin II‑induced myocardial fibrosis cell viability, migration and apoptosis

Jin

et al. 2020

Mol Med Rep

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Angiotensin II (AngII) is a central signaling molecule of the renin-angiotensin system that serves a vital role in myocardial fibrosis (MF). The present study aimed to investigate the effects of matrix metalloproteinase (MMP)3 on MF progression. To induce cellular fibrosis, H9C2 rat myocardial cells were treated with AngII for 24 h. Subsequently, cells were treated with levocarnitine, or transfected with small interfering (si)RNA-negative control or siRNA-MMP3 (1/2/3). Cell viability, apoptosis and migration were assessed by performing Cell Counting Kit-8, flow cytometry and Transwell assays, respectively. Reverse transcription-quantitative PCR (RT-qPCR) and western blotting were performed to determine the expression levels of MF biomarkers, including disease-, apoptosis-and oxidative stress-related genes. Compared with the control group, AngII significantly inhibited H9C2 cell viability and migration, and significantly increased H9C2 cell apoptosis (P<0.05). However, compared with AngII-treated H9C2 cells, MMP3 knockdown significantly inhibited fibrotic H9C2 cell viability and migration, but increased fibrotic H9C2 cell apoptosis (P<0.05). The RT-qPCR results demonstrated that MMP3 knockdown significantly downregulated the expression levels of AXL receptor tyrosine kinase, AngII receptor type 1, α-smooth muscle actin and Collagen I in AngII-treated H9C2 cells (P<0.05). Moreover, compared with AngII-treated cells, MMP3 knockdown significantly decreased Bcl-2 expression levels , but significantly increased caspase-3 and p53 expression levels in AngII-treated cells (P<0.05). Additionally, compared with AngII-treated cells, MMP3 knockdown significantly decreased MMP3, MMP9, STAT3, p22Phox and p47Phox expression levels in AngII-treated cells (P<0.05). The present study indicated that MMP3 knockdown altered myocardial fibroblast cell viability, migration and apoptosis by regulating apoptosis-and oxidative stress-related genes, thus delaying MF progression.

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Digitalis Therapy and Risk of Recurrent Ventricular Tachyarrhythmias and ICD Therapies in Atrial Fibrillation and Heart Failure

Cited by 5 publications

References 36 publications

Effect of Digitalis on ICD or CRT-D Recipients: A Systematic Review and Meta-Analysis

Effect of Digitalis on ICD or CRT-D Recipients: A Systematic Review and Meta-Analysis

Effect of Chronic Digoxin Use on Mortality and Heart Failure Hospitalization in Pulmonary Arterial Hypertension

Matrix metalloproteinase 3 regulates angiotensin II‑induced myocardial fibrosis cell viability, migration and apoptosis

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