Digitalis Therapy in Patients With Ventricular Tachyarrhythmias

Abstract Objective: The study sought to assess the prognostic value of treatment with digitalis on long-term prognosis in patients with ventricular tachyarrhythmias and atrial fibrillation (AF) and/or heart failure (HF).Background: Data regarding outcome of digitalis therapy following ventricular tachyarrhythmias is limited.Methods: A large retrospective registry was used including consecutive patients with episodes of ventricular tachycardia (VT) or fibrillation (VF) from 2002 to 2015. Patients treated with digitalis were compared to patients without. The primary prognostic outcome was all-cause mortality at three years, secondary endpoints comprised of a composite arrhythmic endpoint (i.e., recurrences of ventricular tachyarrhythmias, sudden cardiac death) and cardiac rehospitalization. Kaplan Meier, multivariable cox regression and time trend analyses were applied for statistics.Results: A total of 831 patients were included (20% treated with digitalis and 80% without). At three years, digitalis treatment was not associated with all-cause mortality in patients with ventricular tachyarrhythmias (24% vs. 21%, log rank p=0.736; HR=1.063; 95% CI 0.746-1.515; p=0.736). However, digitalis therapy was associated with increased risk of the composite endpoint (38% vs. 23%; log rank p=0.001; HR=1.719; 95% CI 1.279-2.311; p=0.001) and cardiac rehospitalization (31% vs. 18%; log rank p=0.001; HR=1.829; 95% CI 1.318-2.538; p=0.001) at three years, which was still evident within multivariable Cox regression analyses. Finally, digitoxin was associated with worse prognosis than digoxin.Conclusion: Digitalis therapy was not associated mortality in patients with ventricular tachyarrhythmias, but with increased risk of the composite arrhythmic endpoint and cardiac rehospitalization at three years.

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

Cardiology ◽

10.1159/000497271 ◽

2019 ◽

Vol 142 (3) ◽

pp. 129-140

Author(s):

Tobias Schupp ◽

Michael Behnes ◽

Christel Weiss ◽

Christoph Nienaber ◽

Linda Reiser ◽

...

Keyword(s):

Heart Failure ◽

Atrial Fibrillation ◽

Cox Regression ◽

Ventricular Tachyarrhythmia ◽

Ventricular Tachyarrhythmias ◽

Digitalis Therapy ◽

Kaplan Meier ◽

Prognostic Outcome ◽

First Recurrence ◽

The Impact

Objective: This study sought to assess the impact of treatment with digitalis on recurrences of ventricular tachyarrhythmias in implantable cardioverter defibrillator (ICD) recipients with atrial fibrillation (AF) and heart failure (HF). Background: The data regarding outcomes of digitalis therapy in ICD recipients are limited. Methods: A large retrospective registry was used, including consecutive ICD recipients with episodes of ventricular tachyarrhythmia between 2002 and 2016. Patients treated with digitalis were compared to patients without digitalis treatment. The primary prognostic outcome was first recurrence of ventricular tachyarrhythmia at 5 years. Kaplan-Meier and multivariable Cox regression analyses were applied. Results: A total of 394 ICD recipients with AF and/or HF was included (26% with digitalis treatment and 74% without). Digitalis treatment was associated with decreased freedom from recurrent ventricular tachyarrhythmias (HR = 1.423; 95% CI 1.047–1.934; p = 0.023). Accordingly, digitalis treatment was associated with decreased freedom from appropriate ICD therapies (HR = 1.622; 95% CI 1.166–2.256; p = 0.004) and, moreover, higher rates of rehospitalization (38 vs. 21%; p = 0.001) and all-cause mortality (33 vs. 20%; p = 0.011). Conclusion: Among ICD recipients suffering from AF and HF, treatment with digitalis was associated with increased rates of recurrent ventricular tachyarrhythmias and ICD therapies. However, the endpoints may also have been driven by interactions between digitalis, AF, and HF.

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Clinical outcome of out-of-hospital vs. in-hospital cardiac arrest survivors presenting with ventricular tachyarrhythmias

Heart and Vessels ◽

10.1007/s00380-021-01976-y ◽

2021 ◽

Author(s):

Julian Müller ◽

Michael Behnes ◽

Tobias Schupp ◽

Linda Reiser ◽

Gabriel Taton ◽

...

Keyword(s):

Cardiac Arrest ◽

Propensity Score ◽

Propensity Score Matching ◽

Cox Regression ◽

Prognostic Impact ◽

Ventricular Tachyarrhythmias ◽

Increased Risk ◽

All Cause Mortality ◽

Hospital Cardiac Arrest

AbstractLimited data regarding the prognostic impact of ventricular tachyarrhythmias related to out-of-hospital (OHCA) compared to in-hospital cardiac arrest (IHCA) is available. A large retrospective single-center observational registry with all patients admitted due to ventricular tachyarrhythmias was used including all consecutive patients with ventricular tachycardia (VT) and fibrillation (VF) on admission from 2002 to 2016. Survivors discharged after OHCA were compared to those after IHCA using multivariable Cox regression models and propensity-score matching for evaluation of the primary endpoint of long-term all-cause mortality at 2.5 years. Secondary endpoints were all-cause mortality at 6 months and cardiac rehospitalization at 2.5 years. From 2.422 consecutive patients with ventricular tachyarrhythmias, a total of 524 patients survived cardiac arrest and were discharged from hospital (OHCA 62%; IHCA 38%). In about 50% of all cases, acute myocardial infarction was the underlying disease leading to ventricular tachyarrhythmias with consecutive aborted cardiac arrest. Survivors of IHCA were associated with increased long-term all-cause mortality compared to OHCA even after multivariable adjustment (28% vs. 16%; log rank p = 0.001; HR 1.623; 95% CI 1.002–2.629; p = 0.049) and after propensity-score matching (28% vs. 19%; log rank p = 0.045). Rates of cardiac rehospitalization rates at 2.5 years were equally distributed between OHCA and IHCA survivors. In patients presenting with ventricular tachyarrhythmias, survivors of IHCA were associated with increased risk for all-cause mortality at 2.5 years compared to OHCA survivors.

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Atrial Fibrillation Is Associated with Increased Mortality in Patients Presenting with Ventricular Tachyarrhythmias

Scientific Reports ◽

10.1038/s41598-019-49325-4 ◽

2019 ◽

Vol 9 (1) ◽

Author(s):

Michael Behnes ◽

Jonas Rusnak ◽

Gabriel Taton ◽

Tobias Schupp ◽

Linda Reiser ◽

...

Keyword(s):

Atrial Fibrillation ◽

Cox Regression ◽

Ventricular Tachyarrhythmia ◽

Prognostic Impact ◽

Ventricular Tachyarrhythmias ◽

Lv Dysfunction ◽

Kaplan Meier ◽

All Cause Mortality

Abstract Heterogenous data about the prognostic impact of atrial fibrillation (AF) in patients with ventricular tachyarrhythmias exist. Therefore, this study evaluates this impact of AF in patients presenting with ventricular tachyarrhythmias. 1,993 consecutive patients presenting with ventricular tachyarrhythmias (i.e. ventricular tachycardia and fibrillation (VT, VF)) on admission at one institution were included (from 2002 until 2016). All medical data of index and follow-up hospitalizations were collected during the complete follow-up period for each patient. Statistics comprised univariable Kaplan-Meier and multivariable Cox regression analyses in the unmatched consecutive cohort and after propensity-score matching for harmonization. The primary prognostic endpoint was long-term all-cause mortality at 2.5 years. AF was present in 31% of patients presenting with index ventricular tachyarrhythmias on admission (70% paroxysmal, 9% persistent, 21% permanent). VT was more common (67% versus 59%; p = 0.001) than VF (33% versus 41%; p = 0.001) in AF compared to non-AF patients. Long-term all-cause mortality at 2.5 years occurred more often in AF compared to non-AF patients (mortality rates 40% versus 24%, log rank p = 0.001; HR = 1.825; 95% CI 1.548–2.153; p = 0.001), which may be attributed to higher rates of all-cause mortality at 30 days, in-hospital mortality and mortality after discharge (p < 0.05) (secondary endpoints). Mortality differences were observed irrespective of index ventricular tachyarrhythmia (VT or VF), LV dysfunction or presence of an ICD. In conclusion, this study identifies AF as an independent predictor of death in patients presenting consecutively with ventricular tachyarrhythmias.

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Fibrinogen Concentrate to Cardiac Surgery Patients with Ongoing Bleeding does not Increase the Risk of Thromboembolic Complications or Death

Thrombosis and Haemostasis ◽

10.1055/s-0039-3402759 ◽

2020 ◽

Vol 120 (03) ◽

pp. 384-391 ◽

Cited By ~ 2

Author(s):

Katarina Waldén ◽

Anders Jeppsson ◽

Salmir Nasic ◽

Martin Karlsson

Keyword(s):

Cardiac Surgery ◽

Cox Regression ◽

Composite Endpoint ◽

University Hospital ◽

Sensitivity Analyses ◽

Thromboembolic Complications ◽

Fibrinogen Concentrate ◽

Increased Risk ◽

Significant Difference ◽

Secondary Endpoints

Abstract Background We investigated whether fibrinogen concentrate administration to bleeding patients is associated with an increased risk of thromboembolic complications and death. Methods All consecutive patients who underwent first-time cardiac surgery at Sahlgrenska University Hospital from 2009 to 2014 were included. Patients, who had received fibrinogen concentrate, were compared with those who had not received fibrinogen concentrate. The primary endpoint was a composite of thromboembolic complications and death within 1 year after surgery. Secondary endpoints included the composite and mortality within 30 days and mortality within 1 year after surgery. Multivariable logistic regression and Cox regression models were used to compare the groups. Propensity score (PS)-matched models were used for sensitivity analyses. Results A total of 5,408 patients were included in the present study, of which 564 (10.4%) received fibrinogen concentrate. The composite endpoint occurred in 3.5% of patients at 30 days and 10.5% at 1 year. There was no significant difference between the groups in the composite endpoint at 1 year (adjusted hazard ratio [HR]: 1.11, 95% confidence interval [CI]: 0.84–1.46, p = 0.45) or in the secondary endpoints, that is, mortality at 1 year (adjusted HR: 1.38, 95% CI: 0.93–2.04, p = 0.11), composite at 30 days (adjusted odds ratio [OR]: 1.07, 95% CI: 0.64–1.81, p = 0.79) and mortality at 30 days (adjusted OR: 1.00, 95% CI: 0.51–1.96, p = 0.50). The results of the sensitivity analyses were consistent with those of main analyses. Conclusion Perioperative administration of fibrinogen concentrate to bleeding cardiac surgery patients is not associated with an increased risk of thromboembolic complications or death.

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Macrophage-modulating cytokines predict adverse outcome in heart failure

Thrombosis and Haemostasis ◽

10.1160/th09-06-0399 ◽

2010 ◽

Vol 103 (02) ◽

pp. 435-441 ◽

Cited By ~ 21

Author(s):

Philipp Hohensinner ◽

Kathrin Rychli ◽

Gerlinde Zorn ◽

Martin Hülsmann ◽

Rudolf Berger ◽

...

Keyword(s):

Heart Failure ◽

Mononuclear Cells ◽

Cox Regression ◽

Adverse Outcome ◽

Composite Endpoint ◽

Advanced Heart Failure ◽

Colony Stimulating Factor ◽

Increased Risk ◽

All Cause Mortality ◽

Stimulating Factor

SummaryCytokines regulating the mobilisation, recruitment and survival of mononuclear cells may play an important role in progression of heart failure. Therefore, we investigated the role of granulocyte colony stimulating factor (G-CSF), monocyte chemoattractant protein 1 (MCP-1) and macrophage colony stimulating factor (M-CSF) in patients with advanced heart failure. G-CSF, MCP-1 and M-CSF were determined in plasma of 351 patients with advanced heart failure by specific ELISAs. During a median follow up period of 16 months (95% confidence interval [CI]: 15–17 months) 175 patients (50%) experienced the composite endpoint rehospitalisation and all-cause mortality. M-CSF tertiles were associated with a gradually increasing risk with hazard ratios (HR) of 2.2 (95% CI: 1.5–3.2; for trend, p<0.001) for the composite endpoint and 2.6 (95% CI: 1.5–4.6; for trend, p=0.002) for all-cause mortality comparing third and first tertile. These associations remained significant in a multivariable Cox regression model after adjustment for BNP and other known risk factors (p=0.043 and p=0.024). High MCP-1 concentrations were associated with an increased risk of all-cause mortality with an adjusted HR of 1.9 (third vs. first tertile, 95% CI: 1.1–3.3; for trend, p=0.034). In contrast, G-CSF tertiles were not significantly associated with the composite endpoint or all-cause mortality in multivariable Cox regression. In conclusion, the independent and concentration-dependent association of macrophage-modulating cytokines and in particular of M-CSF with adverse outcome in advanced HF patients suggests that these cytokines may play an important pathophysiological role in progression of cardiomyopathy.

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Metformin use and cardiovascular outcomes after acute myocardial infarction in patients with type 2 diabetes: a cohort study

Cardiovascular Diabetology ◽

10.1186/s12933-019-0972-4 ◽

2019 ◽

Vol 18 (1) ◽

Cited By ~ 4

Author(s):

Daniel I. Bromage ◽

Tom R. Godec ◽

Mar Pujades-Rodriguez ◽

Arturo Gonzalez-Izquierdo ◽

S. Denaxas ◽

...

Keyword(s):

Myocardial Infarction ◽

Type 2 Diabetes ◽

Acute Myocardial Infarction ◽

Composite Endpoint ◽

Care Hospital ◽

Primary Care Hospital ◽

Increased Risk ◽

All Cause Mortality ◽

Secondary Endpoints

Abstract Background The use of metformin after acute myocardial infarction (AMI) has been associated with reduced mortality in people with type 2 diabetes mellitus (T2DM). However, it is not known if it is acutely cardioprotective in patients taking metformin at the time of AMI. We compared patient outcomes according to metformin status at the time of admission for fatal and non-fatal AMI in a large cohort of patients in England. Methods This study used linked data from primary care, hospital admissions and death registry from 4.7 million inhabitants in England, as part of the CALIBER resource. The primary endpoint was a composite of acute myocardial infarction requiring hospitalisation, stroke and cardiovascular death. The secondary endpoints were heart failure (HF) hospitalisation and all-cause mortality. Results 4,030 patients with T2DM and incident AMI recorded between January 1998 and October 2010 were included. At AMI admission, 63.9% of patients were receiving metformin and 36.1% another oral hypoglycaemic drug. Median follow-up was 343 (IQR: 1–1436) days. Adjusted analyses showed an increased hazard of the composite endpoint in metformin users compared to non-users (HR 1.09 [1.01–1.19]), but not of the secondary endpoints. The higher risk of the composite endpoint in metformin users was only observed in people taking metformin at AMI admission, whereas metformin use post-AMI was associated with a reduction in risk of all-cause mortality (0.76 [0.62–0.93], P = 0.009). Conclusions Our study suggests that metformin use at the time of first AMI is associated with increased risk of cardiovascular disease and death in patients with T2DM, while its use post-AMI might be beneficial. Further investigation in well-designed randomised controlled trials is indicated, especially in view of emerging evidence of cardioprotection from sodium-glucose co-transporter-2 (SGLT2) inhibitors.

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Prognostic Significance of Diabetes Mellitus in Patients with Atrial Fibrillation

10.21203/rs.3.rs-137390/v1 ◽

2020 ◽

Author(s):

Andreas S Papazoglou ◽

Anastasios Kartas ◽

Athanasios Samaras ◽

Evangelos Akrivos ◽

Ioannis Vouloagkas ◽

...

Keyword(s):

Diabetes Mellitus ◽

Atrial Fibrillation ◽

Cox Regression ◽

Survival Rates ◽

Prognostic Significance ◽

Composite Outcome ◽

Kaplan Meier ◽

Increased Risk ◽

All Cause Mortality ◽

Hba1c Levels

Abstract Background: There are limited data on the association of diabetes mellitus (DM) and levels of glycated hemoglobin (HbA1c) with outcomes in patients with atrial fibrillation (AF).Methods: This retrospective cohort study included patients who were recently hospitalized with a primary or secondary diagnosis of AF from December 2015 through June 2018. Kaplan-Meier curves and Cox-regression adjusted hazard ratios (aHR) were calculated for the primary outcome of all-cause mortality and for the secondary outcomes of cardiovascular (CV) mortality, stroke and the composite outcome of CV death or hospitalization. Spline curve models were fitted to investigate associations of HbA1c values and mortality among patients with AF and DM.Results: In total 1140 AF patients were included, of whom 373 (32.7%) had DM. During a median follow-up of 2.6 years, 414 (37.3%) patients died. The presence of DM was associated with a higher risk of all-cause mortality (aHR=1.44, 95% confidence intervals [CI]: 1.12-1.85), CV mortality (aHR=1.44, 95% CI: 1.08-1.93), stroke (aHR=2.62, 95% CI: 1.24-5.53) and the composite outcome of hospitalization or CV death (aHR=1.28, 95% CI: 1.06-1.54). In AF patients with comorbid DM, the spline curves showed a positive linear association between HbA1c levels and outcomes, with values 7.6-8.2% being independent predictors of increased all-cause mortality, and values <6.2% predicting significantly decreased all-cause and CV mortality.Conclusions: The presence of DM on top of AF was associated with a 1.5-fold increased risk for all-cause or CV mortality and excess morbidity. HbA1c levels lower than 6.2% were independently related to better survival rates.

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Advanced Liver Fibrosis Predicts Unfavorable Long-Term Prognosis in First-Ever Ischemic Stroke or Transient Ischemic Attack

Cerebrovascular Diseases ◽

10.1159/000510436 ◽

2020 ◽

Vol 49 (5) ◽

pp. 474-480

Author(s):

Minyoul Baik ◽

Hyo Suk Nam ◽

Ji Hoe Heo ◽

Hyung Jong Park ◽

Beom Kyung Kim ◽

...

Keyword(s):

Ischemic Stroke ◽

Liver Fibrosis ◽

Transient Ischemic Attack ◽

Cox Regression ◽

Advanced Fibrosis ◽

Increased Risk ◽

All Cause Mortality ◽

Long Term Prognosis ◽

Ischemic Attack

Introduction: There are a limited number of studies investigating the relationship between the degree of liver fibrosis and the long-term prognosis, especially ischemic stroke (IS) recurrence, in first-ever IS or transient ischemic attack (TIA). Objective: We investigated whether there are differences in the long-term all-cause and cardiovascular mortalities and IS recurrence based on the degree of liver fibrosis in first-ever IS or TIA. Methods: This analysis included 2,504 patients with first-ever IS or TIA recruited from a prospective stroke cohort. Liver fibrosis was predicted using the fibrosis-4 (FIB-4) index, and advanced fibrosis was defined as an FIB-4 index of >3.25. Using Cox regression models, we compared the all-cause and cardiovascular mortalities and IS recurrence. As measures for the additive predictive value of the FIB-4 index for prediction of all-cause mortality, the integrated area under the receiver operating characteristic curve (iAUC), net reclassification improvement (NRI), and integrated discrimination improvement (IDI) were used. Results: There were 231 (9.2%) patients with advanced fibrosis. During a median follow-up of 1.2 years, the cumulative all-cause and cardiovascular mortalities were 6.4 and 1.9%, and IS recurrence was observed in 5.3%. The advanced fibrosis was associated with an increased risk of all-cause mortality (hazard ratio [HR] = 3.98, 95% confidence interval [CI] = 2.40–6.59), cardiovascular mortality (HR = 4.48, 95% CI = 1.59–12.65), and IS recurrence (HR = 1.95, 95% CI = 1.05–3.65). Adding the FIB-4 index to the model consisting of traditional cardiovascular risk factors improved the predictive accuracy for all-cause mortality as measured using the iAUC (from 0.7594 to 0.7729) and for all-cause mortality at 1 year as measured using the NRI (38.6%) and IDI (0.037). Conclusions: The burden of liver fibrosis is associated with unfavorable long-term prognosis, including recurrent IS, in first-ever IS or TIA.

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Sex differences in transaortic flow rate and association with all-cause mortality in patients with severe aortic stenosis

European Heart Journal - Cardiovascular Imaging ◽

10.1093/ehjci/jeab045 ◽

2021 ◽

Author(s):

Sahrai Saeed ◽

Anastasia Vamvakidou ◽

Spyridon Zidros ◽

George Papasozomenos ◽

Vegard Lysne ◽

...

Keyword(s):

Sex Differences ◽

Aortic Stenosis ◽

Flow Rate ◽

Cox Regression ◽

Left Ventricular ◽

Left Ventricular Ejection ◽

Ventricular Ejection Fraction ◽

Cox Regression Analysis ◽

Increased Risk ◽

All Cause Mortality

Abstract Aims It is not known whether transaortic flow rate (FR) in aortic stenosis (AS) differs between men and women, and whether the commonly used cut-off of 200 mL/s is prognostic in females. We aimed to explore sex differences in the determinants of FR, and determine the best sex-specific cut-offs for prediction of all-cause mortality. Methods and results Between 2010 and 2017, a total of 1564 symptomatic patients (mean age 76 ± 13 years, 51% men) with severe AS were prospectively included. Mean follow-up was 35 ± 22 months. The prevalence of cardiovascular disease was significantly higher in men than women (63% vs. 42%, P < 0.001). Men had higher left ventricular mass and lower left ventricular ejection fraction compared to women (both P < 0.001). Men were more likely to undergo an aortic valve intervention (AVI) (54% vs. 45%, P = 0.001), while the death rates were similar (42.0% in men and 40.6% in women, P = 0.580). A total of 779 (49.8%) patients underwent an AVI in which 145 (18.6%) died. In a multivariate Cox regression analysis, each 10 mL/s decrease in FR was associated with a 7% increase in hazard ratio (HR) for all-cause mortality (HR 1.07; 95% CI 1.03–1.11, P < 0.001). The best cut-off value of FR for prediction of all-cause mortality was 179 mL/s in women and 209 mL/s in men. Conclusion Transaortic FR was lower in women than men. In the group undergoing AVI, lower FR was associated with increased risk of all-cause mortality, and the optimal cut-off for prediction of all-cause mortality was lower in women than men.

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Mortality in patients with atrial fibrillation with or without heart failure following hospital discharge

European Heart Journal ◽

10.1093/ehjci/ehaa946.0362 ◽

2020 ◽

Vol 41 (Supplement_2) ◽

Author(s):

A Kartas ◽

A Samaras ◽

D Vasdeki ◽

G Dividis ◽

G Fotos ◽

...

Keyword(s):

Heart Failure ◽

Atrial Fibrillation ◽

Primary Endpoint ◽

Cox Regression ◽

Cross Sectional ◽

Tertiary Center ◽

All Cause Mortality ◽

Endpoint Event ◽

Secondary Endpoints ◽

Sectional Analysis

Abstract Background The association of heart failure (HF) with the prognosis of atrial fibrillation (AF) remains unclear. OBJECTIVES To assess all-cause mortality in patients following hospitalization with comorbid AF in relation to the presence of HF. Methods We performed a cross-sectional analysis of data from 977 patients discharged from the cardiology ward of a single tertiary center between 2015 and 2018 and followed for a median of 2 years. The association between HF and the primary endpoint of death from any cause was assessed using multivariable Cox regression. Results HF was documented in 505 (51.7%) of AF cases at discharge, including HFrEF (17.9%), HFmrEF (16.5%) and HFpEF (25.2%). A primary endpoint event occurred in 212 patients (42%) in the AF-HF group and in 86 patients (18.2%) in the AF-no HF group (adjusted hazard ratio [aHR] 2.27; 95% confidence interval [CI], 1.65 to 3.13; P<0.001). HF was associated with a higher risk of the composite secondary endpoint of death from any cause, AF or HF-specific hospitalization (aHR 1.69; 95% CI 1.32 to 2.16 p<0.001). The associations of HF with the primary and secondary endpoints were significant and similar for AF-HFrEF, AF-HFmrEF, AF-HFpEF. Conclusions HF was present in half of the patients discharged from the hospital with comorbid AF. The presence of HF on top of AF was independently associated with a significantly higher risk of all-cause mortality than did absence of HF, irrespective of HF subtype. Funding Acknowledgement Type of funding source: None

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