Ranolazine Prevents Levosimendan-Induced Atrial Fibrillation

Pharmacology ◽  
2018 ◽  
Vol 102 (3-4) ◽  
pp. 138-141 ◽  
Author(s):  
Christian Ellermann ◽  
Anja Kohnke ◽  
Dirk G. Dechering ◽  
Simon Kochhäuser ◽  
Florian Reinke ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Acute Decompensated Heart Failure ◽  
Experimental Studies ◽  
Decompensated Heart Failure ◽  
Underlying Mechanism ◽  
Limited Range ◽  
Antiarrhythmic Effect ◽  
Additional Treatment ◽  
Right Atrial ◽  
Positive Inotropic Drug

Objectives: Levosimendan is a calcium sensitizer that is used as positive inotropic drug in acute decompensated heart failure. An increased incidence of atrial fibrillation after levosimendan-treatment was observed in clinical and experimental studies. Due to the limited range of antiarrhythmic drugs, the aim of the present study was to assess potential antiarrhythmic effects of ranolazine in levosimendan-pretreated isolated rabbit hearts. Methods: Twelve rabbit hearts were excised and retrogradely perfused employing the Langendorff setup. Left and right atrial catheters were used to record monophasic action potentials and to obtain cycle length-dependent atrial action potential durations (aAPD90) and effective refractory periods (aERP). After obtaining baseline data, 0.5 µmol/L levosimendan was infused. Subsequently, 10 µmol/L ranolazine was administered. Results: Infusion of levosimendan led to a reduction of aAPD90 (–9 ms, p < 0.05) and aERP (–13 ms, p < 0.05). Additional treatment with ranolazine prolonged aAPD90 (+23 ms, p < 0.01) and aERP (+30 ms, p < 0.05). Under baseline conditions, a predefined pacing protocol induced 77 episodes of atrial fibrillation. Infusion of levosimendan enhanced the vulnerability to atrial fibrillation (132 episodes, p = 0.14). Further treatment with ranolazine had a significant antiarrhythmic effect (61 episodes, p < 0.05). Conclusions: In this study, ranolazine seems to prevent atrial fibrillation in levosimendan-pretreated hearts. Underlying mechanism is a prolongation of atrial repolarization and aERP.

scholarly journals Antiarrhythmic effect of ranolazine in combination with selective NCX-inhibition in an experimental model of atrial fibrillation

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
J Wolfes ◽  
C Ellermann ◽  
N Broer ◽  
K Willy ◽  
B Rath ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Experimental Model ◽  
Experimental Studies ◽  
Antiarrhythmic Effect ◽  
Right Atrial ◽  
Cellular Targets ◽  
Refractory Periods ◽  
Group 2 ◽  
Whole Heart ◽  
Group 1

Abstract Background Previous studies showed an antiarrhythmic effect of ranolazine in different clinical and experimental studies. The aim of this study was to investigate the effects of a combination of ranolazine with different selective NCX-inhibitors in an established experimental model of atrial fibrillation. Methods and results 18 hearts of New Zealand white rabbits were retrogradely perfused. Left and right atrial catheters were used to record monophasic action potentials. Hearts were paced at three different cycle lengths (350ms, 250ms, 150ms). Thereby, cycle-length dependent atrial action potential durations (aAPD90), atrial effective refractory periods (aERP) and atrial post-repolarization refractoriness (aPRR=aERP-aAPD90) were obtained. Vulnerability to AF was tested by a standardized protocol employing several trains of burst pacing. After generating baseline data, the hearts were perfused with a combination of acetylcholine (ACh, 1μM) and isoproterenol (Iso, 1μM) to increase occurrence of AF. Afterwards, the hearts were assigned to two groups and additionally perfused with a combination of 10 μM ranolazine and 1 μM of the selective NCX-inhibitor ORM-10103 (group 1: Rano-ORM) or 10 μM ranolazine and 1 μM of another NCX-inhibitor, SEA0400 (group 2: Rano-SEA). Infusion of ACh/Iso led to a shortening of aAPD90 (group 1/2: −27.2ms/−24.5ms p&lt;0.05), aERP (−29.2ms/−35.6ms p&lt;0.05), aPRR (−12.2ms/−13.7ms p=ns) and the occurrence of AF-Episodes was significantly increased (group 1: baseline 6 episodes to 34 episodes under ACh/Iso p&lt;0.05, group 2: baseline 7 episodes to 26 episodes under ACh/Iso p&lt;0.05). Additional perfusion with ranolazine and ORM-10103 did not alter aAPD90 (−0,47ms) while effective refractory periods (+21.4ms, p&lt;0.05) and aPRR (+43ms, p&lt;0.05) were significantly prolonged and AF episodes were effectively reduced to 15 episodes (p&lt;0.05). In group 2, Rano-SEA led to a slight decrease in aAPD90 (−9.5ms) while aERP (+13.3ms, p&lt;0.05) and aPRR (+19.8ms, p&lt;0.05) were prolonged. The occurrence of AF episodes was reduced to 15 episodes (p=0.1). Conclusion To our knowledge this is the first study investigating the effect of ranolazine combined with different selective NCX-inhibitors in an isolated whole-heart model of AF. Atrial repolarization was not significantly changed with either of the combinations. However, both combinations prolonged aERP and aPRR and thereby suppressed induction of AF. Combining novel cellular targets may therefore lead to new potentially interesting options for antiarrhythmic AF therapy that have to be tested in clinical studies. Funding Acknowledgement Type of funding source: None

scholarly journals Serial echocardiographical assessment for urgent control of rapid atrial fibrillation in acute heart failure

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
N Iwahashi ◽  
J Kirigaya ◽  
M Horii ◽  
Y Hanajima ◽  
T Abe ◽  
...  
Keyword(s):  
Heart Failure ◽  
Atrial Fibrillation ◽  
Confidence Interval ◽  
Odds Ratio ◽  
Acute Decompensated Heart Failure ◽  
Decompensated Heart Failure ◽  
Right Heart Catheterization ◽  
Heart Catheterization ◽  
Reduced Ejection Fraction ◽  
Initial Hospitalization

Abstract Objectives Doppler echocardiography is a well-recognized technique for noninvasive evaluation; however, little is known about its efficacy in patients with rapid atrial fibrillation (AF) accompanied by acute decompensated heart failure (ADHF). The aim of this study was to explore the usefulness of serial echocardiographical assessment for rapid AF patients with ADHF. Patients A total of 110 ADHF patients with reduced ejection fraction (HFrEF) and rapid AF who were admitted to the CCU unit and received landiolol treatmentto decrease the heart rate (HR) to &lt;110 bpm and change HR (ΔHR) of &gt;20% within 24 hours were enrolled. Interventions Immediately after admission, the patients (n=110) received landiolol, and its dose was increased to the maximum; then, we repeatedly performed echocardiography. Among them, 39 patients were monitored using invasive right heart catheterization (RHC) simultaneously with echocardiography. Measurements and main results There were significant relationships between Doppler and RHC parameters through the landiolol treatment (Figure, baseline–max HR treatment). We observed for the major adverse events (MAE) during initial hospitalization, which included cardiac death, HF prolongation (required intravenous treatment at 30 days), and worsening renal function (WRF). MAE occurred in 44 patients, and logistic regression analyses showed that the mean left atrial pressure (mLAP)-Doppler (odds ratio = 1.132, 95% confidence interval [CI]: 1.05–1.23, p=0.0004) and stroke volume (SV)-Doppler (odds ratio = 0.93, 95% confidence interval [CI]: 0.89–0.97, p=0.001) at 24 hours were the significant predictors for MAE, and multivariate analysis showed that mLAP-Doppler was the strongest predictor (odds ratio = 1.16, 95% CI: 0.107–1.27, p=0.0005) (Table). Conclusions During the control of the rapid AF in HFrEF patients withADHF, echocardiography was useful to assess their hemodynamic condition, even at bedside. Doppler for rapid AF of ADHF Funding Acknowledgement Type of funding source: None

P4504Pulmonary circulatory-right ventricular uncoupling in acute decompensated heart failure: a key mediator of congestion

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
M Losito ◽  
M Barki ◽  
V Labate ◽  
A Giammarresi ◽  
M Caracciolo ◽  
...  
Keyword(s):  
Heart Failure ◽  
Right Ventricular ◽  
Acute Decompensated Heart Failure ◽  
Decompensated Heart Failure ◽  
Right Atrial ◽  
Maximum Diameter ◽  
Group Iii ◽  
Non Invasive ◽  
Group I ◽  
Group Ii

Abstract Background The degree of congestion in patients hospitalized for acute decompensated heart failure (ADHF) is estimated using traditional non-invasive markers such as echo-derived inferior vena cava diameter (IVCD) and NT-proBNP levels. The deterioration of right ventricular (RV) function and its uncoupling to pulmonary circulation (Pc) represents a turning point in terms of prognosis and clinical outcome in patients affected by heart failure. However, how RV-to-Pc uncoupling correlates with markers of decompensation and congestion in ADHF patients has never been explored. Purpose To investigate, in a cohort of ADHF patients, the association between the degree of RV-to-Pc uncoupling, assessed by the ratio between tricuspid annular plane systolic excursion (TAPSE) to pulmonary artery systolic pressure (PASP), IVCD and right atrial pressure (RAP) estimated at echocardiography. Methods Fourty-six ADHF patients both with reduced and preserved EF (mean age 73.15±10.85 years, 60.8% males) admitted to the Cardiology Department were prospectively enrolled within 24–48 hours from admission. In the acute phase all patients underwent transthoracic echocardiography and laboratory blood tests. Patients were then stratified in tertiles according to TAPSE/PASP ratio (group I: <0.4 mm/mmHg; group II: 0.4 to 0.6 mm/mmHg and group III: >0.6 mm/mmHg) correlating the degree of RV-to-Pc with non-invasive markers of congestion such as NT-proBNP, IVC maximum diameter and RAP. Other echocardiographic parameters including left ventricular (LV) systolic function and LV filling pressures were considered. Results An exponential inverse relationship was found between NT-pro-BNP levels at admission with levels decreasing progressively with the increment of the ratio (Group I: 12828±10600 ng/l; Group II 5549±5383 ng/l; Group III 3695±3870 ng/l; p=0.004) (Figure 1a). An analogous correlation was observed when considering the IVC maximum diameter (Group I: 20.87±5.37 mm; Group II 18.08±4.35 mm; Group III 10.9±3.36 mm; p<0.001) (Figure 1b) and the RAP estimated at echocardiography (Group I: 12.875±5.25 mmHg; Group II 9.157±4.82 mmHg; Group III 4±1.61 mmHg; p<0.001) (Figure 1c). In addition, progressively increasing values of LVEF (Group I: 28±11.3%; Group II 42±17.3%; Group III 49±11.8%; p=0.001) were detected from the lowest to the highest TAPSE/PASP tertiles. No correlation was observed in the three groups for E/E' values at admission (Group I: 17.17±6.7; Group II 19.42±8.36; Group III 15.92±5.7; p=0.5). Figure 1 Conclusions In ADHF, the association between RV to Pc uncoupling, echo-derived measures of congestion and natriuretic peptide levels is here described for the first time. The extent of RV dysfunction in ADHF deserves attention and seems to represent a critical and quite underestimated key mechanism between congestion resolution and in-hospital worsening HF.

Abstract 13532: Comparison of Inferior Vena Cava and Subclavian Vein Collapsibility Index by Ultrasound for Determination of Relative Intravascular Volume in Acute Decompensated Heart Failure

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Yvonne E Kaptein ◽  
Pedro D Salinas ◽  
Payal Sharma ◽  
Ana Christina Perez Moreno ◽  
Nasir Sulemanjee ◽  
...  
Keyword(s):  
Heart Failure ◽  
Inferior Vena Cava ◽  
Subclavian Vein ◽  
Inferior Vena ◽  
Acute Decompensated Heart Failure ◽  
Vena Cava ◽  
Decompensated Heart Failure ◽  
Right Atrial ◽  
Intravascular Volume ◽  
Collapsibility Index

Introduction: Accurate assessment of relative intravascular volume is needed to guide management of acute decompensated heart failure (ADHF). Current assessments include history and physical examination (specific but not sensitive), and N-terminal prohormone of brain natriuretic peptide (NT-proBNP) (sensitive but not specific).Ultrasound (US) of inferior vena cava (IVC) collapsibility with respiration is commonly used to assess intravascular volume and right atrial pressure (RAP) but may be technically challenging. US of subclavian vein (SCV) collapsibility may provide an alternative assessment. Hypothesis: In ADHF, SCV collapsibility index (CI) may correlate with IVC CI and RAP. Methods: Prospective study of non-ventilated patients with ADHF who had NT-proBNP within 24 hours of paired IVC and SCV diameter measurements by US. Results: Forty-two patients (median age 66.5 years, 45% female, and 64% white) were enrolled, with 52 encounters. Cardiovascular comorbidities included hypertension (93%), chronic kidney disease (64%), coronary artery disease (55%), atrial fibrillation/flutter (55%), and valvular disease (55%). Of 38 patients with known heart failure, 63% had HFrEF, 16% HFmrEF, and 21% HFpEF.Correlation of paired IVC CI and SCV CI with relaxed breathing was R = 0.65 (N = 36). Correlation of paired IVC CI and SCV CI with forced inhalation was R = 0.47 (N = 36). Log 10 NT-proBNP was inversely correlated with IVC CI (R = -0.35; N = 51) and SCV CI (R = -0.33; N = 36). For patients with right heart catheterization within 24 hours of US, correlation of RAP to IVC CI was R = -0.53 (N = 9), and RAP to SCV CI was R = -0.65 (N = 9). Moderate or severe tricuspid regurgitation decreased CI independently of intravascular volume and RAP (figure). Conclusions: US measurements of SCV CI correlate well with paired IVC CI in non-ventilated ADHF. RAP by RHC correlated better with SCV CI than with IVC CI. SCV CI may be a reliable alternative to IVC CI in assessing relative intravascular volume.

Abstract 12975: A New Systemic Inflammation-nutrition Index Provides the Additional Long-term Prognostic Information to Ahead Score in Patients With Admitted for Acute Decompensated Heart Failure

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Takahisa Yamada ◽  
Testuya Watanabe ◽  
Takashi Morita ◽  
Yoshio Furukawa ◽  
Shunsuke Tamaki ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Heart Failure ◽  
Atrial Fibrillation ◽  
Systemic Inflammation ◽  
Acute Decompensated Heart Failure ◽  
Decompensated Heart Failure ◽  
Prognostic Information ◽  
Heart Failure Patients ◽  
Ahead Score

Background: Comorbidities are associated with poor clinical outcome in heart failure patients. AHEAD (A: atrial fibrillation; H: hemoglobin; E: elderly; A: abnormal renal parameters; D: diabetes mellitus) score has been related to clinical outcomes in patients with acute decompensated heart failure (ADHF). On the other hand, systemic inflammation plays a critical role in the outcomes of heart failure. Malnutrition is also associated with poor outcome in heart failure patients. It has been recently reported that advanced lung cancer inflammation index (ALI), which is calculated as body mass index х serum albumin / neutrophil to lymphocyte ratio, is an independent prognostic marker in several types of cancer. We sought to investigate the prognostic value of the combination of AHEAD score and ALI in ADHF patients. Methods and Results: We studied 263 patients admitted for ADHF and discharged with survival. At the discharge, we obtained ALI and AHEAD score (range 0-5, atrial fibrillation, hemoglobin <13 mg/dL for men and 12 mg/dL for women, age >70 years, creatinine >130 μmol/L, and diabetes mellitus). During a follow-up period of 5.0±4.2 yrs, 67 patients had cardiovascular death (CVD). At multivariate Cox analysis, AHEAD score and ALI were significantly independently associated with CVD, independently of prior heart failure hospitalization, systolic blood pressure and serum sodium level. The patients with both greater AHEAD score (≥median value=3) and lower ALI (≤median value=42.3) had a significantly increased risk of CVD than those with either and none of them (45% vs 24% vs 13%, p<0.0001, respectively). Conclusion: ALI would provide the additional long-term prognostic information to AHEAD score in patients with ADHF.

A Low-Dose β1-Blocker Effectively and Safely Slows the Heart Rate in Patients with Acute Decompensated Heart Failure and Rapid Atrial Fibrillation

Cardiology ◽  
2013 ◽  
Vol 127 (2) ◽  
pp. 105-113 ◽  
Author(s):  
Shigeki Kobayashi ◽  
Wakako Murakami ◽  
Takeki Myoren ◽  
Hiroki Tateishi ◽  
Shinichi Okuda ◽  
...  
Keyword(s):  
Heart Failure ◽  
Atrial Fibrillation ◽  
Heart Rate ◽  
Low Dose ◽  
Acute Decompensated Heart Failure ◽  
Decompensated Heart Failure
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