scholarly journals Small Conductance Ca2 +-Activated K+ (SK) Channel mRNA Expression in Human Atrial and Ventricular Tissue: Comparison Between Donor, Atrial Fibrillation and Heart Failure Tissue

2021 ◽  
Vol 12 ◽  
Author(s):  
Elisa Darkow ◽  
Thong T. Nguyen ◽  
Marina Stolina ◽  
Fabian A. Kari ◽  
Constanze Schmidt ◽  
...  
Keyword(s):  
Heart Failure ◽  
Atrial Fibrillation ◽  
Sinus Rhythm ◽  
Cardiac Disease ◽  
Differentially Expressed ◽  
Sk Channels ◽  
Expression Levels ◽  
Ventricular Tissue ◽  
Small Conductance ◽  
Selective Target

In search of more efficacious and safe pharmacological treatments for atrial fibrillation (AF), atria-selective antiarrhythmic agents have been promoted that target ion channels principally expressed in the atria. This concept allows one to engage antiarrhythmic effects in atria, but spares the ventricles from potentially proarrhythmic side effects. It has been suggested that cardiac small conductance Ca2+-activated K+ (SK) channels may represent an atria-selective target in mammals including humans. However, there are conflicting data concerning the expression of SK channels in different stages of AF, and recent findings suggest that SK channels are upregulated in ventricular myocardium when patients develop heart failure. To address this issue, RNA-sequencing was performed to compare expression levels of three SK channels (KCNN1, KCNN2, and KCNN3) in human atrial and ventricular tissue samples from transplant donor hearts (no cardiac disease), and patients with cardiac disease in sinus rhythm or with AF. In addition, for control purposes expression levels of several genes known to be either chamber-selective or differentially expressed in AF and heart failure were determined. In atria, as compared to ventricle from transplant donor hearts, we confirmed higher expression of KCNN1 and KCNA5, and lower expression of KCNJ2, whereas KCNN2 and KCNN3 were statistically not differentially expressed. Overall expression of KCNN1 was low compared to KCNN2 and KCNN3. Comparing atrial tissue from patients with AF to sinus rhythm samples we saw downregulation of KCNN2 in AF, as previously reported. When comparing ventricular tissue from heart failure patients to non-diseased samples, we found significantly increased ventricular expression of KCNN3 in heart failure, as previously published. The other channels showed no significant difference in expression in either disease. Our results add weight to the view that SK channels are not likely to be an atria-selective target, especially in failing human hearts, and modulators of these channels may prove to have less utility in treating AF than hoped. Whether targeting SK1 holds potential remains to be elucidated.

Abstract 15198: Predictors of Adverse Cardiovascular Outcomes in Patients With Atrial Fibrillation and Heart Failure With Preserved Systolic Function: A Topcat Americas Post Hoc Analysis

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Sanjeev Saksena ◽  
April Slee ◽  
Dhanunjaya Lakkireddy ◽  
Dipen Shah ◽  
Luigi Di Biase ◽  
...  
Keyword(s):  
Heart Failure ◽  
Atrial Fibrillation ◽  
Sinus Rhythm ◽  
Proportional Hazards ◽  
Systolic Function ◽  
Cox Proportional Hazards ◽  
Study Entry ◽  
Pump Failure ◽  
Death Time ◽  
Arrhythmogenic Substrate

Introduction: Presence of atrial fibrillation (AF) is known to increase mortality and impact cardiovascular(CV) outcomes in heart failure (HF) patients (pts) with preserved systolic function (pEF) but its causes are unknown Hypothesis: We hypothesized that AF presentation & clinical factors impact mode of death & CV outcomes of HFpEF pts in the TOPCAT AMERICAS trial. Methods: We analyzed demographic, clinical, ECG and AF presentation as predictors of CV mortality, sudden death( SCD) and pump failure death(PFD). We examined two AF presentations 1. Pts in sinus rhythm (SR, n=1319) compared to pts in AF (n=446) on ECG at study entry or 2. Pts with no AF event by history or ECG ( n=1007 ) compared to those with any AF event (n=760 ) during a mean follow up period of 2.9 years(yrs). Results: AF pts when compared to the rest of the study population were more likely to be older, male, Caucasian origin, have more alcohol use, diabetes, percutaneous coronary interventions. 5 yr CV mortality was higher in pts with AF on ECG (30%) than those in sinus rhythm (18%, p=0.014) but 5 yr SCD was lower (10% in AF on ECG & 7% in any AF) & comparable to SR (7% & 9% respectively, p=ns). 5 yr PFD was higher (13%) than SR (5%, p=0.007. )Table shows Cox proportional hazards analysis of covariates associated with time to CV death, time to SCD & time to PFD adjusted for baseline imbalances. Conclusions:: 1. CV death risk in HFpEF pts increased with age, in minorities, smokers, diabetics, with lower systolic bp, elevated heart rate & AF on ECG.. 2. SCD was more frequent in males, African Americans & diabetics but was low in both AF & SR, perhaps due to a dominant atrial & limited ventricular arrhythmogenic substrate in HFpEF. 3. PFD in HFpEF increased with age, ECG recorded AF & elevated heart rate.This may reflect importance of atrioventricular synchrony in HFpEF. 4. The recording of AF on ECG at study entry was more strongly associated with CV death & PFD, possibly due to greater AF burden in this group compared to those with any AF even..

P6361Prognostic value of discharge heart rate in acute heart failure patients: more relevant in atrial fibrillation?

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
R Vidal-Perez ◽  
R Agra-Bermejo ◽  
D Pascual-Figal ◽  
F Gude Sampedro ◽  
C Abou Jokh ◽  
...  
Keyword(s):  
Heart Failure ◽  
Atrial Fibrillation ◽  
Heart Rate ◽  
Sinus Rhythm ◽  
Acute Heart Failure ◽  
Left Ventricular Ejection ◽  
Long Term Outcomes ◽  
All Cause Mortality ◽  
One Year

Abstract Background The prognostic impact of heart rate (HR) in acute heart failure (AHF) patients is not well known especially in atrial fibrillation (AF) patients. Purpose The aim of the study was to evaluate the impact of admission HR, discharge HR, HR difference (HRD) (admission- discharge) in AHF patients with sinus rhythm (SR) or AF on long- term outcomes. Methods We included 1398 patients consecutively admitted with AHF between October 2013 and December 2014 from a national multicentric, prospective registry. Logistic regression models were used to estimate the association between admission HR, discharge HR and HR difference and one- year all-cause mortality and HF readmission. Results The mean age of the study population was 72±12 years. Of these, 594 (42.4%) were female, 655 (77.8%) were hypertensive and 655 (46.8%) had diabetes. Among all included patients, 745 (53.2%) had sinus rhythm and 653 (46.7%) had atrial fibrillation. Only discharge HR was associated with one-year all-cause mortality (Relative risk (RR)= 1.182, confidence interval (CI) 95% 1.024–1.366, p=0.022) in SR. In AF patients discharge HR was associated with one-year all-cause mortality (RR= 1.276, CI 95% 1.115–1.459, p≤0.001). We did not observe a prognostic effect of admission HR or HRD on long-term outcomes in both groups. This relationship is not dependent on left ventricular ejection fraction (Figure 1) Effect of post-discharge heart rate Conclusions In AHF patients lower discharge HR, neither the admission nor the difference, is associated with better long-term outcomes especially in AF patients Acknowledgement/Funding Heart Failure Program of the Red de Investigaciόn Cardiovascular del Instituto de Salud Carlos III, Madrid, Spain (RD12/0042) and the Fondo Europeo de

scholarly journals Differentially expressed miRNAs in circulating exosomes between atrial fibrillation and sinus rhythm

2019 ◽  
Vol 11 (10) ◽  
pp. 4337-4348 ◽  
Author(s):  
Suyu Wang ◽  
Jie Min ◽  
Yue Yu ◽  
Liang Yin ◽  
Qing Wang ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Sinus Rhythm ◽  
Differentially Expressed ◽  
Differentially Expressed Mirnas

Prognostic value of the heart rate profile during exercise in patients with atrial fibrillation

2018 ◽  
Vol 25 (15) ◽  
pp. 1634-1641 ◽  
Author(s):  
Kazufumi Aihara ◽  
Yuko Kato ◽  
Shinya Suzuki ◽  
Takuto Arita ◽  
Naoharu Yagi ◽  
...  
Keyword(s):  
Heart Failure ◽  
Atrial Fibrillation ◽  
Heart Rate ◽  
Sinus Rhythm ◽  
Exercise Capacity ◽  
Resting Heart Rate ◽  
Peak Heart Rate ◽  
Chronotropic Response ◽  
Response Peak ◽  
Rate Profile

Aims This study aimed to investigate the correlation of heart rate profile during exercise with exercise capacity and heart failure occurrence in patients with atrial fibrillation compared with patients with sinus rhythm. Methods We analyzed 2231 patients (atrial fibrillation: n = 321, sinus rhythm: n = 1910) who underwent a symptom-limited maximal cardiopulmonary exercise test at our institute. Their heart rate profile during exercise was assessed using peak heart rate and chronotropic response; (peak heart rate−resting heart rate)/(220−age−resting heart rate). The endpoint was the occurrence of heart failure events, defined as hospitalization for heart failure or heart failure-related death. Results There were significant positive correlations of peak heart rate and chronotropic response to peak oxygen consumption, both in atrial fibrillation and sinus rhythm. During a median follow-up period of 1262 (interquartile range 974–2921) days, 117 (5.2%) heart failure events were observed. Multivariate analyses showed that peak heart rate and chronotropic response were statistically significant predictors of heart failure events both in atrial fibrillation (peak heart rate: heart rate 0.975, p = 0.002, chronotropic response: heart rate 0.196, p = 0.003) and in sinus rhythm (peak heart rate: heart rate 0.988, p = 0.036, chronotropic response: heart rate 0.347, p = 0.020). Bivariate models showed that compared with chronotropic response, peak heart rate was a stronger predictor of heart failure in atrial fibrillation, whereas the finding was reversed in sinus rhythm. Conclusion The exercise- heart rate profile was significantly related to exercise capacity and future heart failure events, regardless of rhythm. However, the impacts of peak heart rate and chronotropic response on the endpoint varied according to the cardiac rhythm.

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 Heart rate and long-term mortality according to the presence of sinus rhythm or atrial fibrillation in heart failure patients

2013 ◽  
Vol 34 (suppl 1) ◽  
pp. P1534-P1534
Author(s):  
M. De Antonio ◽  
J. Lupon ◽  
M. Domingo ◽  
E. Zamora ◽  
B. Gonzalez ◽  
...  
Keyword(s):  
Heart Failure ◽  
Atrial Fibrillation ◽  
Heart Rate ◽  
Sinus Rhythm ◽  
Heart Failure Patients ◽  
Long Term Mortality
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