scholarly journals Implications of SGLT Inhibition on Redox Signalling in Atrial Fibrillation

2021 ◽  
Vol 22 (11) ◽  
pp. 5937
Author(s):  
David Bode ◽  
Lukas Semmler ◽  
Christian U. Oeing ◽  
Alessio Alogna ◽  
Gabriele G. Schiattarella ◽  
...  
Keyword(s):  
Heart Failure ◽  
Atrial Fibrillation ◽  
Redox Balance ◽  
Potential Effect ◽  
Redox Signalling ◽  
Cellular Processes ◽  
Atrial Remodelling ◽  
Patients With Diabetes ◽  
Post Hoc ◽  
Insight Into

Atrial fibrillation (AF) is the most common sustained (atrial) arrhythmia, a considerable global health burden and often associated with heart failure. Perturbations of redox signalling in cardiomyocytes provide a cellular substrate for the manifestation and maintenance of atrial arrhythmias. Several clinical trials have shown that treatment with sodium-glucose linked transporter inhibitors (SGLTi) improves mortality and hospitalisation in heart failure patients independent of the presence of diabetes. Post hoc analysis of the DECLARE-TIMI 58 trial showed a 19% reduction in AF in patients with diabetes mellitus (hazard ratio, 0.81 (95% confidence interval: 0.68–0.95), n = 17.160) upon treatment with SGLTi, regardless of pre-existing AF or heart failure and independent from blood pressure or renal function. Accordingly, ongoing experimental work suggests that SGLTi not only positively impact heart failure but also counteract cellular ROS production in cardiomyocytes, thereby potentially altering atrial remodelling and reducing AF burden. In this article, we review recent studies investigating the effect of SGLTi on cellular processes closely interlinked with redox balance and their potential effects on the onset and progression of AF. Despite promising insight into SGLTi effect on Ca2+ cycling, Na+ balance, inflammatory and fibrotic signalling, mitochondrial function and energy balance and their potential effect on AF, the data are not yet conclusive and the importance of individual pathways for human AF remains to be established. Lastly, an overview of clinical studies investigating SGLTi in the context of AF is provided.

scholarly journals Incidence of atrial fibrillation, ischaemic heart disease and heart failure in patients with diabetes

2021 ◽  
Vol 20 (1) ◽  
Author(s):  
Amy Groenewegen ◽  
Victor W. Zwartkruis ◽  
Betül Cekic ◽  
Rudolf. A. de Boer ◽  
Michiel Rienstra ◽  
...  
Keyword(s):  
Heart Failure ◽  
Atrial Fibrillation ◽  
Heart Disease ◽  
Ischaemic Heart Disease ◽  
Incidence Rate ◽  
Diabetes Status ◽  
Increased Risk ◽  
Patients With Diabetes ◽  
Rate Ratios ◽  
Age And Sex

Abstract Background Diabetes has strongly been linked to atrial fibrillation, ischaemic heart disease and heart failure. The epidemiology of these cardiovascular diseases is changing, however, due to changes in prevalence of obesity-related conditions and preventive measures. Recent population studies on incidence of atrial fibrillation, ischaemic heart disease and heart failure in patients with diabetes are needed. Methods A dynamic longitudinal cohort study was performed using primary care databases of the Julius General Practitioners’ Network. Diabetes status was determined at baseline (1 January 2014 or upon entering the cohort) and participants were followed-up for atrial fibrillation, ischaemic heart disease and heart failure until 1 February 2019. Age and sex-specific incidence and incidence rate ratios were calculated. Results Mean follow-up was 4.2 years, 12,168 patients were included in the diabetes group, and 130,143 individuals in the background group. Incidence rate ratios, adjusted for age and sex, were 1.17 (95% confidence interval 1.06–1.30) for atrial fibrillation, 1.66 (1.55–1.83) for ischaemic heart disease, and 2.36 (2.10–2.64) for heart failure. Overall, incidence rate ratios were highest in the younger age categories, converging thereafter. Conclusion There is a clear association between diabetes and incidence of the major chronic progressive heart diseases, notably with heart failure with a more than twice increased risk.

scholarly journals Association of Diabetes With Atrial Fibrillation Phenotype and Cardiac and Neurological Comorbidities: Insights From the Swiss‐AF Study

2021 ◽  
Author(s):  
Arjola Bano ◽  
Nicolas Rodondi ◽  
Jürg H. Beer ◽  
Giorgio Moschovitis ◽  
Richard Kobza ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Myocardial Infarction ◽  
Heart Failure ◽  
Atrial Fibrillation ◽  
Cognitive Impairment ◽  
Unique Identifier ◽  
Cross Sectional ◽  
Patients With Diabetes ◽  
History Of

Background Diabetes is a major risk factor for atrial fibrillation (AF). However, it remains unclear whether individual AF phenotype and related comorbidities differ between patients who have AF with and without diabetes. This study investigated the association of diabetes with AF phenotype and cardiac and neurological comorbidities in patients with documented AF. Methods and Results Participants in the multicenter Swiss‐AF (Swiss Atrial Fibrillation) study with data on diabetes and AF phenotype were eligible. Primary outcomes were parameters of AF phenotype, including AF type, AF symptoms, and quality of life (assessed by the European Quality of Life‐5 Dimensions Questionnaire [EQ‐5D]). Secondary outcomes were cardiac (ie, history of hypertension, myocardial infarction, and heart failure) and neurological (ie, history of stroke and cognitive impairment) comorbidities. The cross‐sectional association of diabetes with these outcomes was assessed using logistic and linear regression, adjusted for age, sex, and cardiovascular risk factors. We included 2411 patients with AF (27.4% women; median age, 73.6 years). Diabetes was not associated with nonparoxysmal AF (odds ratio [OR], 1.01; 95% CI, 0.81–1.27). Patients with diabetes less often perceived AF symptoms (OR, 0.74; 95% CI, 0.59–0.92) but had worse quality of life (β=−4.54; 95% CI, −6.40 to −2.68) than those without diabetes. Patients with diabetes were more likely to have cardiac (hypertension [OR, 3.04; 95% CI, 2.19–4.22], myocardial infarction [OR, 1.55; 95% CI, 1.18–2.03], heart failure [OR, 1.99; 95% CI, 1.57–2.51]) and neurological (stroke [OR, 1.39, 95% CI, 1.03–1.87], cognitive impairment [OR, 1.75, 95% CI, 1.39–2.21]) comorbidities. Conclusions Patients who have AF with diabetes less often perceive AF symptoms but have worse quality of life and more cardiac and neurological comorbidities than those without diabetes. This raises the question of whether patients with diabetes should be systematically screened for silent AF. Registration URL: https://www.clinicaltrials.gov ; Unique Identifier: NCT02105844.

scholarly journals Heart Failure Outcomes in Patients with Diabetes With and Without Atrial Fibrillation – Data From the EMPA-REG OUTCOME Study

2019 ◽  
Vol 28 ◽  
pp. S172
Author(s):  
M. Böhm ◽  
M. Brueckmann ◽  
D. Fitchett ◽  
J. George ◽  
S. Inzucchi ◽  
...  
Keyword(s):  
Heart Failure ◽  
Atrial Fibrillation ◽  
Outcome Study ◽  
Patients With Diabetes

scholarly journals The influence of atrial fibrillation on the levels of NT-proBNP versus GDF-15 in patients with heart failure

2019 ◽  
Vol 109 (3) ◽  
pp. 331-338 ◽  
Author(s):  
Bernadet T. Santema ◽  
Michelle M. Y. Chan ◽  
Jasper Tromp ◽  
Martin Dokter ◽  
Haye H. van der Wal ◽  
...  
Keyword(s):  
Heart Failure ◽  
Atrial Fibrillation ◽  
Sinus Rhythm ◽  
Plasma Levels ◽  
Validation Cohort ◽  
Post Hoc Analysis ◽  
Patients With Heart Failure ◽  
History Of ◽  
Post Hoc ◽  
Multivariable Adjustment

Abstract Background In heart failure (HF), levels of NT-proBNP are influenced by the presence of concomitant atrial fibrillation (AF), making it difficult to distinguish between HF versus AF in patients with raised NT-proBNP. It is unknown whether levels of GDF-15 are also influenced by AF in patients with HF. In this study we compared the plasma levels of NT-proBNP versus GDF-15 in patients with HF in AF versus sinus rhythm (SR). Methods In a post hoc analysis of the index cohort of BIOSTAT-CHF (n = 2516), we studied patients with HF categorized into three groups: (1) AF at baseline (n = 733), (2) SR at baseline with a history of AF (n = 183), and (3) SR at baseline and no history of AF (n = 1025). The findings were validated in the validation cohort of BIOSTAT-CHF (n = 1738). Results Plasma NT-proBNP levels of patients who had AF at baseline were higher than those of patients in SR (both with and without a history of AF), even after multivariable adjustment (3417 [25th–75th percentile 1897–6486] versus 1788 [682–3870], adjusted p < 0.001, versus 2231 pg/mL [902–5270], adjusted p < 0.001). In contrast, after adjusting for clinical confounders, the levels of GDF-15 were comparable between the three groups (3179 [2062–5253] versus 2545 [1686–4337], adjusted p = 0.36, versus 2294 [1471–3855] pg/mL, adjusted p = 0.08). Similar patterns of both NT-proBNP and GDF-15 were found in the validation cohort. Conclusion These data show that in patients with HF, NT-proBNP is significantly influenced by underlying AF at time of measurement and not by previous episodes of AF, whereas the levels of GDF-15 are not influenced by the presence of AF. Therefore, GDF-15 might have additive value combined with NT-proBNP in the assessment of patients with HF and concomitant AF. Graphic abstract

scholarly journals Diabetes is associated with atrial fibrillation phenotype, cardiac and neurological comorbidities: insights from the Swiss-AF study

2021 ◽  
Vol 42 (Supplement_1) ◽  
Author(s):  
A Bano ◽  
N Rodondi ◽  
J Beer ◽  
G Moschovitis ◽  
R Kobza ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Myocardial Infarction ◽  
Heart Failure ◽  
Atrial Fibrillation ◽  
Cognitive Impairment ◽  
Cross Sectional ◽  
Funding Sources ◽  
Patients With Diabetes ◽  
History Of

Abstract Background Diabetes mellitus is a major risk factor for atrial fibrillation (AF). However, it remains unclear whether individual AF phenotype and related comorbidities differ between AF patients with and without diabetes. Purpose To investigate the association of diabetes with AF phenotype, cardiac and neurological comorbidities in patients with documented AF. Methods Participants of the multicenter Swiss-AF study with available data on diabetes and AF phenotype were eligible. The primary outcomes were parameters of AF phenotype, including AF type (paroxysmal vs non-paroxysmal), AF symptoms (yes vs no), and quality of life (assessed by EQ-5D score). The secondary outcomes were cardiac (ie, history of hypertension, myocardial infarction, heart failure) and neurological comorbidities (ie, history of stroke, cognitive impairment). The cross-sectional association of diabetes with these outcomes was assessed using logistic and linear regression. Results were adjusted for age, sex, and cardiovascular risk factors. Results We included 2411 AF patients (27.4% women; median age, 73.6 years). Diabetes was not associated with non-paroxysmal AF (odds ratio [OR]=1.01; 95% confidence interval [CI]=0.81 to 1.27). Patients with diabetes less often perceived AF symptoms (OR=0.73; CI=0.59 to 0.91), but had worse quality of life (predicted mean difference in EQ-5D score: β=−4.54; CI=−6.40 to −2.68) than those without diabetes. Patients with diabetes were more likely to have cardiac comorbidities [history of hypertension (OR=3.04; CI=2.19 to 4.22), myocardial infarction (OR=1.55; CI=1.18 to 2.03), heart failure (OR=1.99; CI=1.57 to 2.51)] and neurological comorbidities [history of stroke (OR=1.39; CI=1.03 to 1.87), cognitive impairment (OR=1.75; CI=1.39 to 2.21)]. Conclusions In the Swiss-AF cohort population, patients with diabetes less often perceived AF symptoms, but had worse quality of life, more cardiac and neurological comorbidities than those without diabetes. These findings have significant clinical implications. The reduced perception of AF symptoms in patients with diabetes might result in a delayed AF diagnosis and consequently more adverse events, especially cardioembolic stroke. This raises the question whether patients with diabetes should be systematically screened for silent AF. Moreover, patients with concomitant AF and diabetes have increased likelihood of comorbidities and therefore deserve more attentive care. FUNDunding Acknowledgement Type of funding sources: None.

scholarly journals HEART FAILURE OUTCOMES IN PATIENTS WITH DIABETES WITH AND WITHOUT ATRIAL FIBRILLATION - DATA FROM THE EMPA-REG OUTCOME STUDY

2019 ◽  
Vol 35 (10) ◽  
pp. S197
Author(s):  
S. Verma ◽  
M. Böhm ◽  
M. Brueckmann ◽  
D. Fitchett ◽  
J. George ◽  
...  
Keyword(s):  
Heart Failure ◽  
Atrial Fibrillation ◽  
Outcome Study ◽  
Patients With Diabetes

scholarly journals Lenient vs. strict rate control in patients with atrial fibrillation and heart failure: a post-hoc analysis of the RACE II study

2013 ◽  
Vol 15 (11) ◽  
pp. 1311-1318 ◽  
Author(s):  
Bart A. Mulder ◽  
Dirk J. Van Veldhuisen ◽  
Harry J.G.M. Crijns ◽  
Jan G.P. Tijssen ◽  
Hans L. Hillege ◽  
...  
Keyword(s):  
Heart Failure ◽  
Atrial Fibrillation ◽  
Rate Control ◽  
Post Hoc Analysis ◽  
Post Hoc

scholarly journals Role of obesity and hypertension in the incidence of atrial fibrillation, ischaemic heart disease and heart failure in patients with diabetes

2021 ◽  
Vol 20 (1) ◽  
Author(s):  
Lucia La Sala ◽  
Antonio E. Pontiroli
Keyword(s):  
Heart Failure ◽  
Atrial Fibrillation ◽  
Primary Care ◽  
Body Mass Index ◽  
Heart Disease ◽  
Ischaemic Heart Disease ◽  
Heart Diseases ◽  
Treatment Of Hypertension ◽  
Patients With Diabetes

AbstractIn a cohort study performed using primary care databases in a General Practitioners Network, Groenewegen et al. report a clear association between diabetes and incidence of the major chronic progressive heart diseases, notably heart failure (Groenewegen et al. in Cardiovasc Diabetol 20:123, 2021). However, no mention is made of body mass index and hypertension in the methods or in the results. Obesity is linked to hypertension and hypertension is a major risk factor for all cardiovascular diseases, and prospective studies have shown that obesity and hypertension contribute significantly to atrial fibrillation in persons with diabetes. The data would be improved by assessing the role of obesity and of hypertension in the incidence of heart diseases in these patients. This would also lead to a better and personalized treatment of patients with diabetes, for instance through weight loss and intensification of treatment of hypertension, to modify the incidence of atrial fibrillation, ischaemic heart disease and heart failure.

scholarly journals Effect of alirocumab on incidence of atrial fibrillation after acute coronary syndromes: insights from ODYSSEY OUTCOMES

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
R Lopes ◽  
P.G Steg ◽  
D.L Bhatt ◽  
V.A Bittner ◽  
A Dauchy ◽  
...  
Keyword(s):  
Heart Failure ◽  
Atrial Fibrillation ◽  
Acute Coronary Syndromes ◽  
Strong Predictor ◽  
Potential Effect ◽  
Major Adverse Cardiovascular Events ◽  
Funding Source ◽  
Private Company ◽  
History Of ◽  
Coronary Syndromes

Abstract Background Atrial fibrillation (AF) is a marker of risk in patients presenting with acute coronary syndromes (ACS). The potential effect of inhibiting proprotein convertase subtilisin/kexin type 9 (PCSK9) on the incidence of AF is unknown. Methods The ODYSSEY OUTCOMES trial compared randomized treatment with the PCSK9 inhibitor alirocumab or placebo in patients with recent ACS and residual dyslipidaemia despite optimal statin therapy. The current analysis determined: 1) whether alirocumab treatment influenced incident AF; 2) whether a history of AF influenced the risk of major adverse cardiovascular events (MACE); and 3) whether there was interaction between AF at baseline and randomized treatment on MACE. AF was determined from the medical history and investigator reports of adverse events. Results Of 18,924 participants, 662 (3.5%) had a history of AF at randomization and 18,262 (96.5%) had no history of AF. Of the latter category, 499 (2.7%) had incident AF. Older age, randomization in South America or Eastern Europe, history of heart failure or myocardial infarction, and higher body mass index were factors associated with incident AF. Treatment with alirocumab or placebo did not influence incident AF (2.2% vs 2.6%, respectively; hazard ratio 0.90, 95% confidence interval 0.75–1.08; Figure). Patients with a history of AF had a greater burden of comorbidities, including cerebrovascular disease, peripheral artery disease, hypertension and heart failure; they also had higher rates of MACE (Table). There was no significant interaction between AF and randomized treatment on risk of MACE (P interaction=0.78) Conclusions Although treatment with alirocumab did not significantly modify the risk of incident AF after ACS in this analysis, future studies with more sensitive and systematic methods of ascertainment may be warranted. History of AF is a strong predictor of risk of recurrent MACE after ACS. Funding Acknowledgement Type of funding source: Private company. Main funding source(s): Sanofi, Regeneron Pharmaceuticals, Inc

scholarly journals Prognostic implications of valvular heart disease in patients with non-valvular atrial fibrillation

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Athanasios Samaras ◽  
Eleni Vrana ◽  
Anastasios Kartas ◽  
Dimitrios V. Moysidis ◽  
Andreas S. Papazoglou ◽  
...  
Keyword(s):  
Heart Failure ◽  
Atrial Fibrillation ◽  
Heart Disease ◽  
Valvular Heart Disease ◽  
Cox Regression ◽  
Wide Spectrum ◽  
Heart Failure Hospitalization ◽  
Prognostic Effect ◽  
History Of ◽  
Post Hoc

Abstract Background Valvular heart disease (VHD) in non-valvular atrial fibrillation (AF) is a puzzling clinical entity. The aim of this study was to evaluate the prognostic effect of significant VHD (sVHD) among patients with non-valvular AF. Methods This is a post-hoc analysis of the MISOAC-AF trial (NCT02941978). Consecutive inpatients with non-valvular AF who underwent echocardiography were included. sVHD was defined as the presence of at least moderate aortic stenosis (AS) or aortic/mitral/tricuspid regurgitation (AR/MR/TR). Cox regression analyses with covariate adjustments were used for outcome prediction. Results In total, 983 patients with non-valvular AF (median age 76 [14] years) were analyzed over a median follow-up period of 32 [20] months. sVHD was diagnosed in 575 (58.5%) AF patients. sVHD was associated with all-cause mortality (21.6%/yr vs. 6.5%/yr; adjusted HR [aHR] 1.55, 95% confidence interval [CI] 1.17–2.06; p = 0.02), cardiovascular mortality (16%/yr vs. 4%/yr; aHR 1.70, 95% CI 1.09–2.66; p = 0.02) and heart failure-hospitalization (5.8%/yr vs. 1.8%/yr; aHR 2.53, 95% CI 1.35–4.63; p = 0.02). The prognostic effect of sVHD was particularly evident in patients aged < 80 years and in those without history of heart failure (p for interaction < 0.05, in both subgroups). After multivariable adjustment, moderate/severe AS and TR were associated with mortality, while AS and MR with heart failure-hospitalization. Conclusion Among patients with non-valvular AF, sVHD was highly prevalent and beared high prognostic value across a wide spectrum of clinical outcomes, especially in patients aged < 80 years or in the absence of heart failure. Predominantly AS, as well as MR and TR, were associated with worse prognosis.

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