Project description:QTc prolongation and torsade de pointes (TdP) are significant adverse events linked to azole antifungals. Reports on QTc interval prolongation caused by these agents are limited. In this study, we report a case of a 77-year-old male with cardiovascular disease who experienced QTc prolongation and subsequent TdP while being treated with fluconazole for Candida albicans-induced knee arthritis. Additionally, a literature review was conducted on cases where QTc prolongation and TdP were triggered as adverse events of azole antifungal drugs. The case study detailed the patient's experience, whereas the literature review analyzed cases from May 1997 to February 2023, focusing on patient demographics, underlying diseases, antifungal regimens, concurrent medications, QTc changes, and outcomes. The review identified 16 cases, mainly in younger individuals (median age of 29) and women (75%). Fluconazole (63%) and voriconazole (37%) were the most common agents. Concurrent medications were present in 75% of cases, and TdP occurred in 81%. Management typically involved discontinuing or switching antifungals and correcting electrolytes, with all patients surviving. Risk assessment and concurrent medication review are essential before starting azole therapy. High-risk patients require careful electrocardiogram monitoring to prevent arrhythmias. Remote monitoring may enhance safety for patients with implanted devices. Further studies are needed to understand risk factors and management strategies.
Project description:BackgroundPatients with end-stage renal disease have very high mortality. In individuals on hemodialysis, cardiovascular deaths account for ~50% of all deaths in this population, mostly due to arrhythmia. To determine the causes of these arrhythmic deaths is essential in order to adopt preventive strategies. The main objective of this study was to investigate whether, the presence of QTc interval alterations, from electrolyte abnormalities or presence of rare genetic variants, could have a relationship with sudden arrhythmogenic deaths in end-stage renal disease patients.MethodsWe recorded the pre- and post-dialysis QTc interval in 111 patients undergoing hemodialysis. In 47 of them, we analyzed 24 SCD-related genes including the most prevalent genes associated with long QT syndrome using a custom resequencing panel.ResultsWe found a positive although not significant association between the presence of long QTc and mortality in a subset of end-stage renal disease patients. In addition, in five patients with long QTc only after dialysis (21.7%) we detected rare potentially pathogenic genetic variants. Three out of these five carriers subsequently died suddenly.ConclusionsGenetic background may be determinant in the risk of sudden cardiac death in these patients. We recommend evaluating the QTc interval before and after hemodialysis, and performing a genetic analysis of individuals with long QTc after hemodialysis.
Project description:Third-degree atrioventricular (AV) block can result in sudden cardiac death if no reliable escape rhythm is present. Here, we report a case of an 86-year-old female patient who developed a third-degree AV block leading to cardiac arrest. Surprisingly, sinus rhythm returned after 4 min of asystole, and she showed complete neurological recovery. Emergency services were contacted by the husband of an 86-year-old woman after she was found unconscious. Ambulance personnel diagnosed a third-degree AV block without an escape rhythm and transcutaneous pacing was started. At arrival on the emergency ward, pacing was inadequate, resulting in absence of circulation for ∼10 min. After consultation with the family, the patient turned out to have signed a 'do not resuscitate' order. Given the impression that the considerable delay deemed favourable neurological recovery unlikely, it was decided together with the family to stop the resuscitation. Subsequently, she had an intermittent junctional escape rhythm but eventually developed a documented asystole of more than 4 min. Against all expectations, she regained sinus rhythm and fully recovered. Eventually, a pacemaker was implanted and she was discharged home without neurological sequalae of the cardiac arrest. Autoresuscitation, also known as the Lazarus syndrome, is the spontaneous return of circulation after cardiac arrest and is incidentally seen after failed cardiopulmonary resuscitation (CPR). Autoresuscitation in the absence of CPR is highly unusual, but could, in this case, be due to the total AV block as the cause of the cardiac arrest.
Project description:Total mortality and sudden cardiac death is highly prevalent in patients with chronic kidney disease (CKD). In CKD patients, the protein-bound uremic retention solute indoxyl sulfate (IS) is independently associated with cardiovascular disease. However, the underlying mechanisms of this association have yet to be elucidated. The relationship between IS and cardiac electrocardiographic parameters was investigated in a prospective observational study among early CKD patients. IS arrhythmogenic effect was evaluated by in vitro cardiomyocyte electrophysiological study and mathematical computer simulation. In a cohort of 100 early CKD patients, patients with corrected QT (QTc) prolongation had higher IS levels. Furthermore, serum IS level was independently associated with prolonged QTc interval. In vitro, the delay rectifier potassium current (IK) was found to be significantly decreased after the treatment of IS in a dose-dependent manner. The modulation of IS to the IK was through the regulation of the major potassium ion channel protein Kv 2.1 phosphorylation. In a computer simulation, the decrease of IK by IS could prolong the action potential duration (APD) and induce early afterdepolarization, which is known to be a trigger mechanism of lethal ventricular arrhythmias. In conclusion, serum IS level is independently associated with the prolonged QTc interval in early CKD patients. IS down-regulated IK channel protein phosphorylation and the IK current activity that in turn increased the cardiomyocyte APD and QTc interval in vitro and in the computer ORd model. These findings suggest that IS may play a role in the development of arrhythmogenesis in CKD patients.
Project description:BackgroundThere is limited pharmacologic therapy to reduce the QT interval in hereditary long QT syndrome (LQTS).Case summaryWe describe a child with Allan-Herndon-Dudley syndrome, Lennox-Gastaut epileptic syndrome (LGS), and LQTS Type 1 (LQTS1). Rufinamide was added to his antiepileptic medications to improve seizure control and was noted to be associated with a marked improvement in electrocardiogram QT interval. To the best of our knowledge, this is the first reported case of successful pharmacologic shortening of the QT interval in LQTS1.DiscussionThis case report highlights the potential benefits of rufinamide, a drug associated with mild QT shortening in normal individuals, to markedly reduce and normalize QT duration in a subject with LQTS1.
Project description:To investigate the effects of the combination of extracorporeal cardiopulmonary resuscitation and thrombolytic therapy on the recovery of vital organ function after prolonged cardiac arrest.Laboratory investigation.University laboratory.Pigs.Animals underwent 30-minute untreated ventricular fibrillation cardiac arrest followed by extracorporeal cardiopulmonary resuscitation for 6 hours. Animals were allocated into two experimental groups: t-extracorporeal cardiopulmonary resuscitation (t-ECPR) group, which received streptokinase 1 million units, and control extracorporeal cardiopulmonary resuscitation (c-ECPR), which did not receive streptokinase. In both groups, the resuscitation protocol included the following physiologic targets: mean arterial pressure greater than 70 mm Hg, cerebral perfusion pressure greater than 50 mm Hg, PaO2 150 ± 50 torr (20 ± 7 kPa), PaCO2 40 ± 5 torr (5 ± 1 kPa), and core temperature 33°C ± 1°C. Defibrillation was attempted after 30 minutes of extracorporeal cardiopulmonary resuscitation.A cardiac resuscitability score was assessed on the basis of success of defibrillation, return of spontaneous heart beat, weanability from extracorporeal cardiopulmonary resuscitation, and left ventricular systolic function after weaning. The addition of thrombolytic to extracorporeal cardiopulmonary resuscitation significantly improved cardiac resuscitability (3.7 ± 1.6 in t-ECPR vs 1.0 ± 1.5 in c-ECPR). Arterial lactate clearance was higher in t-ECPR than in c-ECPR (40% ± 15% vs 18% ± 21%). At the end of the experiment, the intracranial pressure was significantly higher in c-ECPR than in t-ECPR. Recovery of brain electrical activity, as assessed by quantitative analysis of electroencephalogram signal, and ischemic neuronal injury on histopathologic examination did not differ between groups. Animals in t-ECPR group did not have increased bleeding complications, including intracerebral hemorrhages.In a porcine model of prolonged cardiac arrest, t-ECPR improved cardiac resuscitability and reduced brain edema, without increasing bleeding complications. However, early electroencephalogram recovery and ischemic neuronal injury were not improved.
Project description:The aetiology of sudden cardiac arrest can often be identified to underlying cardiac pathology. Mitral valve prolapse is a relatively common valvular pathology with symptoms manifesting with increasing severity of mitral regurgitation (MR). It is unusual for severe MR to be present without symptoms, and there is growing evidence that this subset of patients may be at increased risk of sudden cardiac arrest or death. The difficulty lies in identifying those patients at risk and applying measures that are appropriate to halting progression to cardiac arrest. This article examines the association of mitral valve prolapse with cardiac arrests, the underlying pathophysiological process and the strategies for identifying those at risk.
Project description:BackgroundA prolonged PR interval is common among cardiac resynchronization therapy (CRT) candidates; however, the association between PR interval and outcomes is unclear, and the data are conflicting.MethodsWe conducted inverse probability weighted analyses of 26 451 CRT-eligible (ejection fraction ≤35, QRS ≥120 ms) patients from the National Cardiovascular Data Registry ICD Registry to assess the association between a prolonged PR interval (≥230 ms), receipt of CRT with defibrillator (CRT-D) versus implantable cardioverter defibrillator (ICD), and outcomes. We first tested the association between a prolonged PR interval and outcomes among patients stratified by device type. Next, we performed a comparative effectiveness analysis of CRT-D versus ICD among patients when stratified by PR interval. Using Medicare claims data, we followed up with patients up to 5 years for incident heart failure hospitalization or death.ResultsPatients with a PR≥230 ms (15%; n=4035) were older and had more comorbidities, including coronary artery disease, atrial arrhythmias, diabetes mellitus, and chronic kidney disease. After risk adjustment, a PR≥230 ms (versus PR<230 ms) was associated with increased risk of heart failure hospitalization or death among CRT-D (hazard ratio, 1.23; 95% confidence interval, 1.14-1.31; P<0.001) but not ICD recipients (hazard ratio, 1.08; 95% confidence interval, 0.97-1.20; P=0.17) (Pinteraction=0.043). CRT-D (versus ICD) was associated with lower rates of heart failure hospitalization or death among patients with PR<230 ms (hazard ratio, 0.79; 95% confidence interval, 0.73-0.85; P<0.001) but not PR≥230 ms (hazard ratio, 1.01; 95% confidence interval, 0.87-1.17; P=0.90) (Pinteraction=0.0025).ConclusionsA PR≥230 ms is associated with increased rates of heart failure hospitalization or death among CRT-D patients. The real-world comparative effectiveness of CRT-D (versus ICD) is significantly less among patients with a PR≥230 ms in comparison with patients with a PR<230 ms.
Project description:Two studies (ROADMAP and ORIENT) evaluating the renoprotective effects of olmesartan medoxomil (OM) in patients with type 2 diabetes suggested OM is associated with increased cardiovascular mortality. We conducted a thorough QTc study to evaluate the effects of OM on cardiac repolarization. A randomized, double-blind, phase 1 study was conducted per E14 Guidance to assess the effects of single doses of OM therapeutic dose (40 mg), OM supratherapeutic dose (160 mg), placebo, or moxifloxacin (MOXI; 400 mg) on QTc in 56 healthy subjects. The primary endpoint was the baseline-adjusted, placebo-corrected QTc interval using Fridericia's formula (ΔΔQTcF) for OM and MOXI. Assay sensitivity was concluded if lower limit of 1-sided 95%CI > 5 milliseconds of ΔΔQTcF for MOXI. No threshold pharmacologic effect for OM was concluded if upper limit of 1-sided 95%CI <10 milliseconds for ΔΔQTcF at any timepoint. Pharmacokinetics, ECGs, and safety were assessed. Assay sensitivity was demonstrated. The largest upper limit of the 1-sided 95%CI for ΔΔQTcF was <5 milliseconds for OM. No clinically significant changes were observed in ECGs. Pharmacokinetics and safety profile were consistent with previous data. Therapeutic and supratherapeutic OM doses had no clinically significant effect on cardiac repolarization and were well tolerated.