Prolonged Corrected QT Research Articles

Comparison of sparfloxacin and ciprofloxacin in the treatment of community-acquired acute uncomplicated urinary tract infection in women

Urinary tract infection (UTI) is a common illness, with ≥30% of all women experiencing a UTI during their lifetime. Less than a decade ago, the standard therapy for acute uncomplicated UTIs involved treatment with ≥7 days of an antibacterial agent, but recent studies using a variety of newly introduced antibiotics, including the fluoroquinolones, have demonstrated that a 1- to 5-day treatment regimen can be equally effective. This randomized, double-masked, multicenter study was conducted to compare the efficacy and tolerability of a single dose of sparfloxacin with those of a 3-day regimen of sparfloxacin and a 7-day regimen of ciprofloxacin in the treatment of women with community-acquired acute uncomplicated urinary tract infection. A total of 1175 women were enrolled; 395 received sparfloxacin as a single 400-mg dose on day 1, 394 received sparfloxacin as a 400-mg loading dose on day 1 followed by 200 mg once daily for 2 additional days, and 386 received ciprofloxacin 250 mg twice daily for 7 days. Patients were comparable with respect to demographic characteristics and underlying conditions. A total of 954 patients were clinically assessable; 490 of these were also bacteriologically assessable. All patients treated were included in the tolerability analysis. Escherichia coli (75.4%), Klebsiella pneumoniae (4.9%), Enterococcus faecalis (4.6%), and Staphylococcus saprophyticus (4.1%) were the most commonly isolated organisms. In the all-treated population, clinical success was achieved 5 to 9 days after therapy in 91.8%, 92.2%, and 91.6% of patients in the single-dose sparfloxacin, 3-day sparfloxacin, and 7-day ciprofloxacin groups, respectively; bacteriologic success was observed in 91.7%, 92.6%, and 96.6% of those in the 3 groups. Sustained clinical success rates 4 to 6 weeks after therapy were 76.6%, 80.2%, and 79.5% in the single-dose sparfloxacin, 3-day sparfloxacin, and 7-day ciprofloxacin groups, respectively; sustained bacteriologic success rates were 80.7%, 90.1%, and 92.6%. The most common adverse events were nausea, headache, vaginal thrush, dizziness, and diarrhea; >92% of adverse events were mild or moderate in severity. The 2 drugs had comparable frequencies of adverse events, except for photosensitivity, which occurred in 3.3% of the 3-day sparfloxacin group, 1.3% of the single-dose sparfloxacin group, and 0.3% of the ciprofloxacin group ( P = 0.005). The 3-day sparfloxacin regimen was effective and well tolerated. The initial response to single-dose sparfloxacin treatment was comparable to the response to the other 2 regimens, but the single-dose regimen proved less effective over time, with higher rates of clinical recurrence and bacteriologic relapse. Sparfloxacin provides an alternative to ciprofloxacin for patients with acute uncomplicated urinary tract infection who are not at risk for photosensitivity reactions or adverse events associated with a prolonged corrected QT interval.

Prolonged QT interval predicts cardiac and all-cause mortality in the elderly. The Rotterdam Study.

To examine the association between heart-rate corrected QT prolongation and cardiac and all-cause mortality in the population-based Rotterdam Study among men and women aged 55 years or older and to compare the prognostic value of the QT interval, using different formulas to correct for heart rate. After exclusion of participants with arrhythmias or bundle branch block on the ECG, the study population consisted of 2083 men and 3158 women. The QT interval was computed by the Modular ECG Analysis System (MEANS). Data were analysed using Cox' proportional hazards model. Participants in the highest quartile of the heart-rate corrected QT interval had about a 70% age- and sex-adjusted increased risk for both all-cause mortality (hazard ratio (HR) 1.8; 95% CI:1.3-2.4) and cardiac mortality (HR 1.7; 95% CI:1.0-2.7) compared to those in the lowest quartile. In women, the increased risk associated with prolonged QT for cardiac death was more pronounced than in men. These risk estimates did not change after adjustment for potential confounders, including history of myocardial infarction, hypertension and diabetes mellitus. A prolonged heart-rate corrected QT interval is an independent predictor for cardiac and all-cause mortality in older men and women. The risk associated with prolonged QT is hardly affected by the heart-rate correction formula used.

The relation between QTc interval prolongation and diabetic complications. The EURODIAB IDDM Complication Study Group.

The prevalence of QT interval prolongation is higher in people with diabetes and its complications. Sudden death has been reported as a common cause of death in insulin-dependent diabetic patients affected by autonomic neuropathy. It has been postulated that QT prolongation predisposes to cardiac arrhythmias and sudden death. In this analysis the prevalence of QT interval prolongation and its relation with diabetic complications were evaluated in the EURODIAB IDDM Complications Study (3250 insulin-dependent diabetic patients attending 31 centres in 16 European countries). Five consecutive RR and QT intervals were measured with a ruler on the V5 lead of the resting ECG tracing and the QT interval corrected for the previous cardiac cycle length was calculated according to the Bazett's formula. The prevalence of an abnormally prolonged corrected QT was 16% in the whole population, 11% in males and 21 % in females (p < 0.001). The mean corrected QT was 0.412 s in males and 0.422 s in females (p < 0.001). Corrected QT duration was independently associated with age, HbA1c and blood pressure. Corrected QT was also correlated with ischaemic heart disease and nephropathy but this relation appeared to be stronger in males than in females. Male patients with neuropathy or impaired heart rate variability or both showed a higher mean adjusted corrected QT compared with male patients without this complication. The relation between corrected QT prolongation and autonomic neuropathy was not observed among females. In conclusion we have shown that corrected QT in insulin-dependent diabetic female patients is longer than in male patients, even in the absence of diabetic complications known to increase the risk of corrected QT prolongation.

Consultation with the Specialist: The Long QT Syndrome

Consultation with the Specialist: The Long QT Syndrome

Arrhythmias after astemizole overdose

Astemizole, a relatively new H1 blocker, has been reported to cause ventricular arrhythmias in the poisoned patient. We present two cases of astemizole poisoning, one with asystole followed by ventricular fibrillation occurring 11 hours after ingestion treated with defibrillation and one with an isolated finding of a prolonged corrected QT interval. Electrocardiogram monitoring to detect conduction defects can identify patients at risk of developing life-threatening arrhythmias.

Comparison of QT dispersion in hypertrophic cardiomyopathy between patients with and without ventricular arrhythmias and sudden death

Recent studies have suggested that interlead QT variability on the surface electrocardiogram, defined as QT dispersion, may reflect regional variations in myocardial recovery of excitability.1-4 The finding of a decreased QT dispersion in patients with different heart diseases treated with class III agents, sotalo13 and amiodarone,5T6 further supports this theory. A significant QT dispersion was found both in patients with congenital and acquired long QT interva12,5,7%s and in patients with myocardial infarction. 2,3,g~10 In hypertrophic cardiomyopathy (HC), the presence of electrical instability is a potentially important determinant of sudden death.“-l3 The pathologic substrate of the disease may create the conditions for QT interval prolongation and nonhomogeneous recovery of excitability.14 Dritsas et all5 recently showed a prolonged corrected QT interval (QTc) and increased QTc dispersion in 24 patients with HC compared with normal subjects, but a comparison between patients with and without ventricular arrhythmias was not done. This study assesses QT dispersion in HC patients with and without documented serious ventricular arrhythmias and sudden death. Twenty-six patients with NC (19 males and 7 females, mean age 37 t- 13 years, range 8 to 57) attending our institution for outpatient follow-up evaluation, or referred for risk stratification

Cardiotoxic effects of astemizole overdose in children

Astemizole, a nonsedating antihistamine, caused a prolonged corrected QT interval, ventricular dysrhythmias, and atrioventricular heart block after overdose in five children. Cardiotoxic effects lasted an average of 2 1/2 days. Children poisoned with astemizole need emergent medical evaluation, a 12-lead electrocardiogram with calculation of the corrected QT interval, and continuous cardiac monitoring for 24 hours.

Optic Disk Cupping and Electrocardiographic Abnormalities in an American Pedigree with Leber's Hereditary Optic Neuropathy

We examined the clinical characteristics of affected and unaffected members of an American black family with the 11778 mitochondrial DNA mutation associated with Leber's hereditary optic neuropathy. Thirty-six individuals from four generations were included. All maternally related subjects were shown to be essentially homoplasmic for the 11778 mitochondrial DNA mutation in blood. Paternally related subjects did not carry this mutation. Patients affected with optic neuropathy had optic nerve head cupping. Loss of unmyelinated axons from the prelaminar optic nerve may be responsible for cupping in these patients. Electrocardiographic analysis of subjects carrying the 11778 mitochondrial DNA mutation disclosed statistically significant (P = .02) prolongation of the corrected OT interval as compared to control subjects. While the clinical significance of this magnitude of corrected QT prolongation is unknown, it may represent a systemic manifestation of the 11778 mutation. No electrocardiographic evidence of preexcitation syndromes was seen.

The congenital long QT syndromes in childhood

Twenty-three children and young persons with a congenital long QT syndrome were identified; the median age at the time of referral was 10 years (range 4 days to 19 years) and 14 patients (61%) had a family history of the syndrome. Among the 19 patients with symptoms, the initial symptom was syncope in 13 (69%), aborted sudden death in 5 (26%) and near drowning in 1 (5%). There were three deaths during a combined follow-up period of 67 patient-years (average annual mortality rate 4.5%). Patients who did not respond to therapy with a beta-adrenergic blocker and those who died were significantly younger than the remaining patients at the time of diagnosis (p ≤ 0.05 for both).Analysis of 44 treadmill exercise tests performed by 16 patients revealed significant prolongation of the median corrected QT (QTc) interval in response to exercise, with maximal prolongation present after 2 min of recovery (median QTc interval 0.52 s versus a baseline value of 0.47 s, p < 0.001). Characteristic changes in T wave configuration were noted in 8 of 15 patients on at least one occasion during ambulatory Holter electrocardiographic monitoring, including T wave alternation in two patients, both of whom died shortly afterward.It is suggested that the congenital long QT syndrome is associated with a significant mortality rate in childhood despite the use of conventional therapy in symptomatic patients. Ambulatory Holter monitoring and treadmill exercise testing may be helpful, both in confirming the diagnosis of a long QT syndrome and in monitoring the adequacy of treatment. Children presenting with sustained ventricular arrhythmias appear to merit early consideration of dual therapy (beta-blockade plus cardiac pacemaker or left cardiac sympathectomy).

Medical Complications of Eating Disorders in Adolescents

Anorexia nervosa and bulimia are occurring with increased frequency among adolescents and preadolescents. To determine the range and severity of medical complications encountered in younger anorectic and bulimic patients, we reviewed the medical records of 65 adolescents and preadolescents, aged 10 to 20 years, who were observed in the Eating Disorders Clinic of the Children's Hospital at Stanford. Significant medical instability was present in the majority of our patients. A total of 55% of anorectic patients and 22% of bulimic patients required hospitalization for medical reasons during the study period. Cardiovascular abnormalities were frequent, including bradycardia, prolonged corrected QT intervals, dysrhythmias, and marked orthostatic pulse and BP instability. Hypothermia, with temperatures less than 35.5 degrees C, was common. Renal abnormalities included pyuria, hematuria, and proteinuria. Electrolyte derangements occurred in patients who vomited or purged. Hypokalemia was most common, but hypocalcemia, hypomagnesemia, and hypophosphatemia were also noted. The majority of our pediatric patients with eating disorders had evidence of physiologic derangement requiring medical intervention. The need for adolescents and preadolescents with eating disorders to receive ongoing medical monitoring in concert with psychiatric treatment and the need for therapists and medical practitioners to become familiar with the potential medical sequelae of eating disorders are underscored by our data.

Hypokalemia as a cause of cardiac arrest: Results of electrophysiologic testing and long-term follow-up

Hypokalemia is known to cause malignant ventricular arrhythmias.‘.” It is occasionally discovered in patients resuscitated from cardiac arrest.“-: Do these patients require antiarrhythmic drug therapy or is maintenance of normal potassium levels adequate to prevent recurrent cardiac arrest? We performed electrophysiologic studies in 10 patients with cardiac arrest associated with hypokalemia. The clinical and laboratory features are summarized in Table I. Six patients presented with ventricular fibrillation, two presented with monomorphic ventricular tachycardia, and two presented with polymorphic ventricular tachycardia with morphologic features suggesting torsade de pointes. Six patients had at least one episode of polymorphic ventricular tachycardia on post resuscitation rhythm strips. All had diuretic induced hypokalemia (2.2 to 3.3 mEq/L) and all had prolonged corrected QT intervals

Biochemical evidence of myocardial injury after severe head trauma

Serum levels of creatine kinase (CK) and its myocardial isoenzyme (CK-MB) were measured and serial ECG recorded in 24 male and 6 female patients with severe head trauma. All patients were comatose, but no patient sustained a spinal or chest injury. Total CK activity was elevated in at least one sample in each patient. Elevated CK-MB activity was found in 28 patients. The serial CK-MB data did not follow the same pattern as that of patients suffering from myocardial infarctions. The mean CK-MB remained elevated for at least 3 days after injury, although individual patterns were variable. ECG abnormalities included prolonged corrected QT interval (QTc) in 90% and a variety of nonspecific ST segment and T wave changes in 53%. These ECG findings are consistent with other clinical studies of severe neurological disorders, particularly cerebrovascular accidents. The elevated CK-MB activity indicates that ongoing myocardial damage occurs in patients with severe head injury. Although the underlying mechanism is not entirely clear, an excessive release of catecholamines is the most likely mechanism accounting for diffuse myocardial damage, prolonged elevated CK-MB values and the observed ECG abnormalities.

Retinal detachment due to macular holes.

<h3>Objective</h3> To evaluate the extent of hydroxychloroquine-induced corrected QT (QTc) prolongation and its relation to COVID-19 infection severity and incidence of polymorphic ventricular arrhythmias and sudden arrhythmic deaths. <h3>Design</h3> A large-scale cohort study with retrospective analysis of baseline and on-therapy QT interval corrected using Bazett and Fridericia formulas. <h3>Setting</h3> A multicentre study involving eight secondary and tertiary care hospitals of the Abu Dhabi Health Services Company (SEHA), United Arab Emirates. <h3>Participants</h3> 2014 patients consecutively admitted with PCR-confirmed SARS-CoV-2 infection between 1 March 2020 and 1 June 2020. <h3>Interventions</h3> Treatment with hydroxychloroquine alone or in combination with azithromycin for at least 24 hours and with a baseline ECG and at least one ECG after 24 hours of therapy. <h3>Main outcome measures</h3> Maximal QTc interval prolongation and its relationship to clinical severity, polymorphic ventricular tachycardia and sudden arrhythmic death while on treatment. <h3>Results</h3> The baseline QTc_(Bazett) was 427.6±25.4 ms and the maximum QTc_(Bazett) during treatment was 439.2±30.4 ms (p&lt;0.001). Severe QTc prolongation (QTc ≥500 ms) was observed in 1.7%–3.3% of patients (Fridericia and Bazett, respectively). There were no cases of polymorphic ventricular arrhythmia or hydroxychloroquine-related arrhythmic death. QTc prolongation was more pronounced in combination therapy compared with hydroxychloroquine alone (22.2 ms vs 11.0 ms, p&lt;0.001) and in patients with higher COVID-19 clinical severity (asymptomatic: 428.4±25.4 ms, severe COVID-19 infection: 452.7±35.7 ms, p&lt;0.001). The overall in-hospital mortality was 3.97% and deceased patients had longer on-therapy QTc_(Bazett) than survivors (459.8±21.4 ms vs 438.4±29.9 ms, p&lt;0.001). <h3>Conclusions</h3> The incidence of severe QTc prolongation with hydroxychloroquine was low and not associated with ventricular arrhythmia. The safety concerns surrounding the use of hydroxychloroquine may have been overestimated; however, caution should be exercised when using hydroxychloroquine in patients with risk factors for QT prolongation.