Ranolazine as you have never seen it before: an antiarrhythmic for atrial fibrillation

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
J.P Sousa ◽  
L Puga ◽  
J Ribeiro ◽  
J Lopes ◽  
C Saleiro ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Cohort Studies ◽  
Meta Analysis ◽  
Rhythm Control ◽  
Current Evidence ◽  
Qtc Interval ◽  
Interval Prolongation ◽  
Qtc Interval Prolongation ◽  
Secondary Endpoints

Abstract Background Currently available pharmacological options for rhythm control in atrial fibrillation (AF) are overshadowed by suboptimal efficacy and both frequent and potentially severe adverse events. Recent studies have added evidence to the hypothesis that ranolazine might exert antiarrhythmic effects, particularly in atrial tachyarrhythmias. Purpose To perform a systematic review with meta-analysis in order to ascertain the potential role of ranolazine in the management of AF. Methods We systematically searched MEDLINE, Embase and Scopus for randomized controlled trials (RCTs) and cohort studies addressing the association between ranolazine and AF outcomes, published up until December 1, 2019. The primary endpoint was incidence of AF, which was evaluated under a ranolazine versus placebo design. In this regard, patients in the setting of postcardiac surgery were further investigated separately. Secondary endpoints included AF cardioversion outcomes, which were addressed through comparison between ranolazine plus amiodarone and amiodarone alone for proportional efficacy and temporal requirements (time-to-cardioversion). The latter analysis was also undertaken in a dose-sensitive fashion (≤1000mg vs. 1500mg of ranolazine). Tertiary endpoints covered AF burden and episodes, in paroxysmal AF patients, and safety outcomes, namely death, QTc interval prolongation and hypotension. Study-specific odds ratios (ORs) were pooled using meta-analytic techniques with a random-effects model. Results A total of 10 RCTs comprising 8.109 participants and 3 cohort studies encompassing 37.112 patients were regarded as eligible for evaluation. Ranolazine was found to attenuate patients' odds of developing AF (OR 0.53, 95% CI: 0.41–0.69, p<0.001, i2=58%). This effect held true, with an even larger effect size, in the context of post-cardiac surgery (OR 0.34, 95% CI: 0.16–0.72, p=0.005, i2=64%). Ranolazine increased the chances of successful AF cardioversion when added to amiodarone over amiodarone alone (OR 6.67, 95% CI: 1.49–29.89, p=0.01, i2=76%), while significantly reducing time-to-cardioversion [SMD 9.54h, 95% CI: −13.3–5.75, p<0.001, i2=99%]. Interestingly, cardioversion was faster with ≤1000mg of ranolazine (SMD −13.16h, 95% CI: −15.07–11.25, p<0.001, i2=95%) than with 1500mg (SMD −3.57h, 95% CI: −5.06–2.08, p<0.001, i2=23%). In paroxysmal AF, ranolazine was also proved to significantly reduce both AF burden and episodes. There were no safety signals regarding mortality odds, QTc interval prolongation (mostly clinically insignificant) and hypotension (mostly transitory). Conclusion Current evidence suggests that ranolazine provides an effective and safe option for a chemical rhythm control strategy in AF management, a field in which medical breakthroughs are desperately needed. Funding Acknowledgement Type of funding source: None

Role of Co-occurring Alcohol and Substances Abuse on QTc Interval Prolongation Among Psychiatric Patients: A Cross-sectional National Survey

2017 ◽  
Vol 41 (S1) ◽  
pp. S201-S202
Author(s):  
M. Corbo ◽  
T. Acciavatti ◽  
F. Fiori ◽  
R. Santacroce ◽  
A. Aguglia ◽  
...  
Keyword(s):  
National Survey ◽  
Psychotropic Drugs ◽  
Polymorphic Ventricular Tachycardia ◽  
Qtc Interval ◽  
Interval Prolongation ◽  
Qtc Prolongation ◽  
Cross Sectional ◽  
Star Network ◽  
Qtc Interval Prolongation

IntroductionQTc interval prolongation is considered a risk factor for fatal polymorphic ventricular tachycardia, which can result in sudden cardiac death. Most psychotropic drugs have a dose-dependent potential to prolong the QTc interval. However, other factors require appropriate consideration, including: age; gender; other medications; electrolyte abnormalities; severe comorbid conditions, such as co-occurring alcohol or substances abuse/dependence.ObjectivesThe objective was to study the potential mediating roles of alcohol/substances abuse on QTc prolongation.AimsThe Italian research group STAR Network, in collaboration with the Young Italian Psychiatrists Association, aimed to evaluate the frequency of QTc interval prolongation in a sample of patients under treatment with psychotropic drugs through a cross-sectional national survey.MethodsA sample of 2411 unselected patients were enrolled after performing an ECG during the recruitment period. Sociodemographic and clinical characteristics were collected from medical records. Collected data underwent statistical analysis.ResultsA total of 11.2% of patients reported alcohol abuse, and only 8.9% psychotropic substances. According to the threshold, less than 20% of patients had a borderline value of QTc, and 1% a pathological value. Patients with co-occurring alcohol misuse and drug abuse were more likely to have longer QTc interval.ConclusionsThe present study describes the frequency of QTc prolongation in real-world clinical practice. Before prescribing a psychotropic drug, the physician should carefully assess its risks and benefits to avoid this type of adverse reaction, particularly when additional risk factors are present. The potential role of alcohol and substances on QTc length could be particularly useful in emergency settings.Disclosure of interestThe authors have not supplied their declaration of competing interest.

scholarly journals Cost-Effectiveness of Catheter Ablation for Rhythm Control of Atrial Fibrillation

2013 ◽  
Vol 2013 ◽  
pp. 1-11 ◽  
Author(s):  
Gord Blackhouse ◽  
Nazila Assasi ◽  
Feng Xie ◽  
Kathryn Gaebel ◽  
Kaitryn Campbell ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Cost Effectiveness ◽  
Catheter Ablation ◽  
Willingness To Pay ◽  
Normal Sinus Rhythm ◽  
Meta Analysis ◽  
Cost Effective ◽  
Rhythm Control ◽  
Current Evidence ◽  
Normal Sinus

Objective. The objective of this study is to evaluate the cost-effectiveness of catheter ablation for rhythm control compared to antiarrhythmic drug (AAD) therapy in patients with atrial fibrillation (AF) who have previously failed on an AAD.Methods. An economic model was developed to compare (1) catheter ablation and (2) AAD (amiodarone 200 mg/day). At the end of the initial 12 month phase of the model, patients are classified as being in normal sinus rhythm or with AF, based on data from a meta-analysis. In the 5-year Markov phase of the model, patients are at risk of ischemic stroke each 3-month model cycle.Results. The model estimated that, compared to the AAD strategy, ablation had $8,539 higher costs, 0.033 fewer strokes, and 0.144 more QALYS over the 5-year time horizon. The incremental cost per QALY of ablation compared to AAD was estimated to be $59,194. The probability of ablation being cost-effective for willingness to pay thresholds of $50,000 and $100,000 was estimated to be 0.89 and 0.90, respectively.Conclusion. Based on current evidence, pulmonary vein ablation for treatment of AF is cost-effective if decision makers willingness to pay for a QALY is $59,194 or higher.

scholarly journals Protective role of cardiac-specific overexpression of caveolin-3 in cirrhotic cardiomyopathy

2020 ◽  
Vol 318 (3) ◽  
pp. G531-G541 ◽  
Author(s):  
So Yeon Kim ◽  
Kang Ho Kim ◽  
Jan M. Schilling ◽  
Joseph Leem ◽  
Mehul Dhanani ◽  
...  
Keyword(s):  
Liver Transplantation ◽  
Protective Role ◽  
Qtc Interval ◽  
Interval Prolongation ◽  
Cirrhotic Cardiomyopathy ◽  
Contractile Responses ◽  
Cardiac Contractile ◽  
Qtc Interval Prolongation

Cirrhotic cardiomyopathy is a clinical syndrome in patients with liver cirrhosis characterized by blunted cardiac contractile responses to stress and/or heart rate-corrected QT (QTc) interval prolongation. Caveolin-3 (Cav-3) plays a critical role in cardiac protection and is an emerging therapeutic target for heart disease. We investigated the protective role of cardiac-specific overexpression (OE) of Cav-3 in cirrhotic cardiomyopathy. Biliary fibrosis was induced in male Cav-3 OE mice and transgene negative (TGneg) littermates by feeding a diet containing 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC; 0.1%) for 3 wk. Liver pathology and blood chemistries were assessed, and stress echocardiography, telemetry, and isolated heart perfusion studies to assess adrenergic responsiveness were performed. Cav-3 OE mice showed a similar degree of hyperdynamic contractility, pulmonary hypertension, and QTc interval prolongation as TGneg mice after 3 wk of DDC diet. Blunted systolic responses were shown in both DDC-fed Cav-3 OE and TGneg hearts after in vivo isoproterenol challenge. However, QTc interval prolongation after in vivo isoproterenol challenge was significantly less in DDC-fed Cav-3 OE hearts compared with DDC-fed TGneg hearts. In ex vivo perfused hearts, where circulatory factors are absent, isoproterenol challenge showed hearts from DDC-fed Cav-3 OE mice had better cardiac contractility and relaxation compared with DDC-fed TGneg hearts. Although Cav-3 OE in the heart did not prevent cardiac alterations in DDC-induced biliary fibrosis, cardiac expression of Cav-3 reduced QTc interval prolongation after adrenergic stimulation in cirrhosis. NEW & NOTEWORTHY Prevalence of cirrhotic cardiomyopathy is up to 50% in cirrhotic patients, and liver transplantation is the only treatment. However, cirrhotic cardiomyopathy is associated with perioperative morbidity and mortality after liver transplantation; therefore, management of cirrhotic cardiomyopathy is crucial for successful liver transplantation. This study shows cardiac myocyte specific overexpression of caveolin-3 (Cav-3) provides better cardiac contractile responses and less corrected QT prolongation during adrenergic stress in a cirrhotic cardiomyopathy model, suggesting beneficial effects of Cav-3 expression in cirrhotic cardiomyopathy.

scholarly journals QTc interval prolongation and life-threatening arrhythmias during hospitalization in patients with COVID-19. Results from a multi-center prospective registry

2020 ◽  
Author(s):  
Francesco Santoro ◽  
Francesco Monitillo ◽  
Pasquale Raimondo ◽  
Agostino Lopizzo ◽  
Gaetano Brindicci ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Heart Rate ◽  
Antiviral Therapy ◽  
Paroxysmal Atrial Fibrillation ◽  
Qtc Interval ◽  
Interval Prolongation ◽  
Heart Rates ◽  
Basal Heart Rate ◽  
Qtc Interval Prolongation ◽  
Life Threatening

Abstract Background Prolonged QTc interval and life-threatening arrhythmias (LTA) are potential drug induced complications previously reported with antimalarial, antivirals and antibiotics. Objectives To evaluate prevalence and predictors of QTc interval prolongation and incidence of LTA during hospitalization for COVID-19 among patients with normal admission QTc. Methods 110 consecutive patients were enrolled in a multicenter international registry. 12-lead ECG was performed at admission, after 7 and 14 days; QTc values were analyzed. Results Fifteen (14%) patients developed a prolonged-QTc (pQT) after 7 days (mean QTc increase 66±20msec, +16%, p<0.001); these patients were older, had higher basal heart rates, higher rates of paroxysmal atrial fibrillation, lower platelet count. QTc increase was inversely proportional to baseline QTc levels and leukocyte count and directly to basal heart rates(p<0.01).At multivariate stepwise analysis including age, male gender, paroxysmal atrial fibrillation, basal QTc values, basal heart rate and dual antiviral therapy, age(OR 1.06, 95% C.I. 1.00-1.13, p<0.05), basal heart rate(OR 1.07, 95% C.I. 1.02-1.13, p<0.01) and dual antiviral therapy(OR 12.46, 95% C.I. 2.09-74.20, p<0.1) were independent predictors of QT-prolongation.Incidence of LTA during hospitalization was 3.6%. One patient experienced cardiac arrest and three non-sustained ventricular tachycardia. LTAs were recorded after a median of 9 days from hospitalization and were associated with 50% of mortality rate. Conclusions After 7 days of hospitalization, 14% of patients with Covid-19 developed pQTc; age, basal heart rate and dual antiviral therapy were found as independent predictor of pQTc. Life threatening arrhythmias have an incidence of 3.6% and were associated with poor outcome.

scholarly journals QT Interval Prolongation Associated with Intramuscular Ziprasidone in Chinese Patients: A Case Report and a Comprehensive Literature Review with Meta-Analysis

2014 ◽  
Vol 2014 ◽  
pp. 1-8 ◽  
Author(s):  
Xian-Bin Li ◽  
Yi-Lang Tang ◽  
Wei Zheng ◽  
Chuan-Yue Wang ◽  
Jose de Leon
Keyword(s):  
Assessment Tool ◽  
Meta Analysis ◽  
Chinese Patients ◽  
Close Monitoring ◽  
Qtc Interval ◽  
Interval Prolongation ◽  
Qt Interval Prolongation ◽  
Qtc Interval Prolongation ◽  
First Time ◽  
Careful Screening

Intramuscular (IM) ziprasidone has been associated with QTc interval prolongations in patients with preexisting risk factors. A 23-year-old male Chinese schizophrenia patient experienced an increase of QTc interval of 83 milliseconds (ms) after receiving 20 mg IM ziprasidone (baseline and increased QT/QTc were, respectively, 384/418 and 450/501). This was rated as a probable adverse drug reaction (ADR) by the Liverpool ADR causality assessment tool. A systematic review including all types of trials reporting the effect of IM ziprasidone on the QTc interval prolongation identified 19 trials with a total of 1428 patients. Mean QTc change from baseline to end of each study was −3.7 to 12.8 ms after IM ziprasidone. Four randomized trials (3 of 4 published in Chinese) were used to calculate a meta-analysis of QTc interval prolongation which showed no significant differences between IM ziprasidone and IM haloperidol groups (risk ratio 0.49 to 4.31, 95% confidence interval 0.09 to 19.68,P= 0.06 to 0.41). However, our review included two cases of patients who experienced symptoms probably related to QTc prolongation after IM ziprasidone. Thus, careful screening and close monitoring, including baseline ECG, should be considered in patients receiving IM ziprasidone for the first time.

scholarly journals Prognostic Efficacy of Tumor-Stroma Ratio in Women With Breast Cancer: A Meta-Analysis of Cohort Studies

2021 ◽  
Vol 11 ◽  
Author(s):  
Pengli Jiang ◽  
Yulong Chen ◽  
Bin Liu
Keyword(s):  
Breast Cancer ◽  
Cohort Studies ◽  
Meta Analysis ◽  
Disease Free Survival ◽  
Tumor Stroma ◽  
Current Evidence ◽  
Cancer Specific Survival ◽  
Free Survival ◽  
Prognostic Predictor

BackgroundTumor-stroma ratio (TSR) has been suggested as an emerging prognostic predictor in women with breast cancer. However, previous studies evaluating the association between TSR and survival in women with breast cancer showed inconsistent results. We performed a meta-analysis to systematically evaluate the possible prognostic role of TSR in breast cancer.MethodsRelevant cohort studies were obtained via search of PubMed, Embase, and Web of Science databases. A random-effects model, which incorporated the potential heterogeneity, was used to pool the results.ResultsTwelve cohort studies with 6175 patients were included. Nine of the 12 studies used 50% as the cutoff to divide the patients into those with stroma-rich (low TSR) and stroma-poor (high TSR) tumors. Pooled results showed that compared women with stroma-poor tumor, those with stroma-rich tumor were associated with worse survival outcomes (disease-free survival [DFS]: hazard ratio [HR] = 1.56, 95% confidence interval [CI]: 1.32 to 1.85, P < 0.001; overall survival [OS]: HR = 1.67, 95% CI: 1.46 to 1.91, P < 0.001; and cancer-specific survival [CSS]: HR = 1.75, 95% CI: 1.40 to 2.20, P < 0.001). Analysis limited to women with triple-negative breast cancer (TNBC) showed consistent results (DFS: HR: 2.07, 95% CI: 1.59 to 2.71, P < 0.001; OS: HR: 2.04, 95% CI: 1.52 to 2.73, P < 0.001; and CSS: HR: 2.40, 95% CI: 1.52 to 3.78, P < 0.001).ConclusionsCurrent evidence from retrospective studies supports that tumor TSR is a prognostic predictor or poor survival in women with breast cancer.

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