QTc Time Research Articles

Combined gating and trafficking defect in Kv11.1 manifests as a malignant long QT syndrome phenotype in a large Danish p.F29L founder family

Background. Congenital long QT syndrome (LQTS) is a hereditary cardiac channelopathy characterized by delayed ventricular repolarization, syncope, torsades de pointes and sudden cardiac death. Thirty-three members of five apparently ‘unrelated’ Danish families carry the KCNH2:c.87C> A; p.F29L founder mutation. Methods and Results. Linkage disequilibrium mapping with microsatellites around KCNH2 enabled us to estimate the age of the founder mutation to be approximately 22 generations, corresponding to around 550 years. Neighbouring-Joining analysis disclosed one early and three later nodes. The median QTc time of the carriers was 490 ms (range: 415–589 ms) and no difference was seen between the different branches of the family. The mutation is malignant with a penetrance of 73%. Ten F29L carriers received implantable defibrillators (ICDs) (median age at implant 20 years), and of those four individuals experienced eight appropriate shocks. Patch-clamp analysis in HEK 293 cells, performed at 34°C disclosed a loss-of-function phenotype with fast deactivation, reduced steady-state inactivation current density and a positive voltage shift in inactivation. Western blotting of HEK 293 cells transfected with KCNH2:WT and KCNH2:c.87C> A revealed a reduced fraction of fully glycosylated hERG:p.F29L suggesting that this mutation results in defective trafficking. Conclusion. The altered channel gating kinetics in combination with defective trafficking of mutated channels is expected to result in reduced repolarizing current density and, thus, a LQTS phenotype.

Hyperbaric oxygen therapy reduces the risk of QTc interval prolongation in patients with diabetes and hard-to-heal foot ulcers

AimsHeart rate corrected QT (QTc) interval prolongation is a risk factor associated with increased mortality. Hyperbaric oxygen therapy (HBO) has previously been shown to have acute beneficial effects on QTc dispersion. The aim of this study was to evaluate long-term effects of HBO on QTc time in diabetic patients with hard-to-heal foot ulcers. MethodsIn a prospective, double-blinded placebo-controlled study, patients were randomized to 40 treatment sessions with either HBO or air (placebo), at 2.5 ATA. Patients fulfilling >35 completed treatment sessions were included in the evaluation. ResultsOf the initial 75 patients (38 HBO/37 placebo), two were excluded due to pacemaker use. Baseline characteristics were similar between groups. At the 2-year follow-up, QTc time was significantly shorter in the HBO compared to the placebo group (438 vs. 453ms, p<0.05). Further, fewer HBO treated patients had a QTc time >450ms (22 vs. 53 %, p<0.02). This difference seemed to be caused by a significant prolongation of the QTc interval in the placebo group (427 (419–459) at baseline vs. 456ms (424–469) after 2years), whereas no significant change was seen in HBO treated patients. ConclusionsHBO treatment might protect against QTc prolongation in this high-risk diabetic population.

Effects of three month nasal continuous positive airway pressure treatment on electrocardiographic, echocardiographic and overnight polysomnographic parameters in newly diagnosed moderate/severe obstructive sleep apnea patients.

The objective of the study was to determine the effects of nasal continuous positive airway pressure (nCPAP) therapy on left ventricular (LV) function and electrocardiographic parameters in newly diagnosed moderate/severe obstructive sleep apnea (OSA) patients without cardiovascular comorbidities and medical treatments. We examined 44 patients who underwent overnight polysomnography together with 24-hour Holter electrocardiography, cardiopulmonary exercise testing including heart rate recovery at 1 minute (HRR-1), echocardiography, surface electrocardiography, and those who were diagnosed with moderate/severe OSA apnea--hypopnea index ≥ 15. After 3 months of nCPAP treatment, the above-mentioned examinations were repeated. Forty-four patients completed the treatment period. Twelve weeks on effective nCPAP induced a significant increase in the mitral E/A ratio (P = 0.001), as well as reductions in isovolumic relaxation time (P = 0.001) and mitral deceleration time (DT) (P = 0.002). There were no significant differences in LV ejection fraction, LV mass index, and pulsed wave Doppler parameters. Mean heart rate was 79.2 ± 12.5 pulses/minute, maximum P-wave duration 117.5 ± 8.6 msec, P-wave dispersion (PWd) 54.6 ± 10.2 msec, corrected QT interval (QTc) 436.5 ± 40.5 msec, and QT dispersion (QTd) 46.3 ± 7.1 msec, which significantly decreased to 70.4 ± 9.6 pulses/minute (P < 0.001), 111.5 ± 8.7 msec (P < 0.001), 51.6 ± 8.9 msec (P < 0.001), 418.4 ± 31.2 msec (P < 0.001), and 33.8 ± 3.4 msec (P < 0.001), respectively. Exercise capacity at baseline determined as 10.5 ± 2.2 metabolic equivalents (METS) and HRR-1 (20.6 ± 11.7 bpm) significantly increased (12.1 ± 1.5 METS and 27.4 ± 8.6 bpm). There was no significant difference in aortic root parameters. Three-month nCPAP therapy significantly increased LV shortening fraction, with no effect on systolic function or aortic root diameters and a positive effect on heart rate, PWd, HRR-1, QTc and QTd time following nCPAP therapy.

Hypoglykämie und Herzrhythmusstörungen bei Patienten mit Diabetes Typ 2

Hypoglycemia is a common and potentially life-threatening adverse effect of inappropriate diabetes treatment. Typical cardiac complications are ischemia with angina pectoris, myocardial infarction, stroke and arrhythmias, such as atrial fibrillation (AF), ventricular tachycardia and heart failure. Elderly multimorbid patients with type 2 diabetes and polypharmacy and/or cardiac autonomous neuropathy represent a very high risk group for cardiovascular complications associated with hypoglycemia. Targets for glycemic control have to be adapted to the risk of hypoglycemia with a priority of stable glucose homeostasis without rapid fluctuations. Elderly patients with diabetes have a >20% risk of AF. At blood glucose levels of <3mmol/l with a duration of >30min, prolongation of QTc time and ventricular tachycardia occur with an increased risk of ventricular fibrillation and sudden death. Ventricular arrhythmias and AF significantly increase mortality in patients with heart failure. Rapid fluctuations with a mean amplitude of glucose excursion (MAGE) >5mmol/l promote vulnerability of electrical stability of the heart, particularly in frail patients with preexisting coronary heart disease and autonomic neuropathy. Antihyperglycemic agents, such as metformin, acarbose and sodium glucose cotransporter 2 (SGLT2) inhibitors have only a low risk of severe hypoglycemia. Dipeptidyl peptase 4 (DPP-IV) inhibitors and glucagon-like peptide 1 (GLP1) analogues as insulin secretagogues have a lower risk for hypoglycemia than sulfonylurea and insulin. Early basal insulin treatment in patients insufficiently controlled with metformin is efficient, safe and convenient. Targets for glucose control and HbA1c have to be individualized and the choice of drugs must be risk-adjusted. Risk of hypoglycemia should be used as guide in decision-making for safe treatment of diabetes.

Pathologic Q Waves and Prolonged QTc Time in Preoperative ECG Are Predictive for Perioperative Cardiovascular Events

Aims: The value of ECG in the perioperative risk stratification under modern treatment options is uncertain. The main objective of the present analysis was to determine the usefulness of a pre-operative ECG derivation for evaluating the risk of perioperative morbidity and mortality. Methods: We performed a secondary analysis of the prospective, international, multicenter, observational “No-Risk” Study (N-terminal B-type natriuretic peptide [NT-proBNP] for the assessment of the perioperative cardiac risk after major noncardiac surgery) to determine the prognostic value of 12-lead ECG. Inclusion criteria were age >55 years and at least one of the following cardiovascular risk factors: arterial hypertension, diabetes mellitus, dyslipidemia, active smoking, and family history positive for coronary heart disease. The combined primary endpoint included total mortality, acute myocardial infarction (NSTEMI and STEMI), cardiopulmonary resuscitation, heart failure, and asystole or ventricular fibrillation during hospitalization. ECGs from 616 patients enrolled from 2006 to 2009 prior to noncardiac surgery in the No-Risk Study were analyzed. Results: The mean age was 67.6 (±8.1) years; 300 (48.7%) patients were male. Fourteen (2.3%) patients suffered from the combined primary endpoint while in the hospital. In Kaplan-Meier analyses, a pathologic Q wave and QTc > 500 ms were significantly related to the incidence of the primary endpoint (p p = 0.042, respectively), whereas other ECG parameters such as LBBB, RBBB, PQ interval, QRS interval, and others were not related to worse in-hospital outcome. Conclusion: The 12-lead ECG is still an important diagnostic tool for perioperative risk assessment of cardiovascular events in noncardiac surgery in patients at risk.

Prolonged QT interval by methadone: Relevance for daily practice? A prospective study in patients with cancer and noncancer pain

Increased methadone use in patients with pain has raised concerns that the effect of methadone on the QT interval duration and the potential risk of torsades de pointes (TdP) has been underestimated. Most studies on prolonged QT intervals by methadone are performed in maintenance patients; however, doses of methadone in pain treatment are much lower. Hardly any studies have prospectively addressed QT interval prolongation by methadone in patients with pain, and this study aims to address this literature gap. In a period of 3 years, while 130 patients used methadone as pain treatment at a stable dose for at least 1 week, 12-lead electrocardiograms (ECGs) were performed. Corrected QT times, demographic features, methadone dose, duration of therapy, and relevant comedication were documented. The findings included 50 percent of 130 patients, with a mean methadone dose of 18.2 mg/d, were potentially at risk for TdP. Beyond this, 5 percent were at definite risk for TdP. No correlations were found between QTc and gender, age, serum potassium or magnesium levels, methadone dose, underlying disease, or comedication. The study found that in our patients with pain, with relatively low doses of methadone, 5 percent had QTc times ≥500 ms and were thus at serious at risk for TdP. ECGs have to be made in all patients with methadone therapy 1 week after introducing methadone (or after dosage increases).

The impact of metabolic control and QTc prolongation on all-cause mortality in patients with type 2 diabetes and foot ulcers

The increased all-cause mortality in patients with chronic diabetic foot ulcers cannot fully be explained by traditional cardiovascular risk factors. The significance of heart-rate-corrected QT (QTc) prolongation, a finding often seen in these patients, is unknown. Recently, the importance of metabolic control and hypoglycaemia has been discussed. The aim of this study was to evaluate the impact of different HbA1c levels and QTc prolongation on all-cause mortality in the high-risk population of patients with type 2 diabetes mellitus and foot ulcers. All patients with type 2 diabetes, younger than 80 years, visiting our diabetes foot unit, with a foot ulcer duration >4 weeks, were screened for participation. Patients on dialysis were excluded. Patients were grouped according to HbA1c level and QTc time ≤ or > 440 ms. Patients (n = 214, median age 69.1 years) were grouped according to HbA1c level (HbA1c < 7.5% [<58 mmol/mol] n = 81, 7.5-8.9% [58-74 mmol/mol] n = 70, >8.9% [>74 mmol/mol] n = 63). Baseline characteristics, including use of potential hypoglycaemic drugs, were similar between groups. During the 8 years of follow-up 151 patients died (70.6%) and HbA1c < 7.5% (<58 mmol/mol) was strongly associated with increased mortality. The highest mortality was seen in patients with a combination of HbA1c < 7.5% (<58 mmol/mol) and QTc prolongation, with an 8 year mortality of 92.1% as compared with 48.8% in those with HbA1c < 7.5% (<58 mmol/mol) but without QTc prolongation. CONCLUSION/INTERPRETATIONS: HbA1c < 7.5% (<58 mmol/mol) in a high-risk population of patients with type 2 diabetes and foot ulcers is associated with a significantly higher mortality, particularly in patients with QTc prolongation.

Diltiazemin Ondansetron ile Birlikte Kullanımının Anestezi Almış Sıçan Elektrokardiyografisi Üzerindeki Etkisinin Değerlendirilmesi

Objective: This study investigated the changes in electrocardiograms in rats after combined use of ondansetron and diltiazem. Material and Methods: Seventeen rats were included in the study but data were collected from 11 rats with available data. After anesthesia, electrocardiogram records of rats for the initial 5 minutes were considered ''Baseline'' record. Following this, rats received intravenous ondansetron injection and their electrocardiograms were recorded for another 5 minutes. The same procedure was repeated with intravenous diltiazem injection. Results: After ondansetron injection QTc from 9 rats were longer and 2 rats were shorter compared to baseline (before the administration of ondansetron). When diltiazem was given after ondansetron, in 10 rats out of 11, the QTc time was correlated negatively with measurements obtained before diltiazem. There was no statistically significant difference between the baseline QTc measurements and the QTc obtained after the administration of diltiazem. Conclusion: The combined use of ondansetron and diltiazem does not lead to any change in rat electrocardiography.

Investigation of the protective effects of L-carnitine and L-arginine on cardiovascular changes induced by ACTH and dexamethasone in rabbits

To determine the protective effects of L-carnitine on cardiovascular changes that may occur in rabbits treated with adrenocorticotropic hormone (ACTH) and dexamethasone (DEX). Materials and methods: Rabbits of equal weight were divided into 7 groups with 6 animals in each. Blood samples were collected from all groups on days 1, 7, and 14, and blood pressure values and ECG monitoring were recorded. Nitric oxide (NO), creatine kinase MB (CK-MB), and troponin I (TnI) levels were determined in blood samples. Heart rate, QT, and corrected QT (QTc) values were calculated from ECG records. Results: The QT and QTc times were prolonged significantly (P < 0.001) in the ACTH-treated groups compared to the control group, and L-carnitine had no protective effect. Moreover, CK-MB (P < 0.05) and TnI (P < 0.001) levels were higher in the ACTH-treated groups than they were in the control group. Conclusion: Application of ACTH results in prolongation of QT and QTc intervals and increases in CK-MB and TnI levels, which are indicators of heart muscle damage.

Analysis of pro-arrhythmic effects induced by different routes of administration of bone marrow stem cells

There has been repeated concern that intramyocardial (i.m.) delivery of cells could cause ventricular arrhythmias. The aim of the study was to evaluate the pro-arrhythmic effects of bone marrow stem cell (BMSC) injection and compare different routes of administration. An ischemia reperfusion injury was induced in New Zealand rabbits by temporal ligation of anterior descending coronary artery. Homologous BMSCs were isolated, cultured and re-suspended for injection. We compared different routes of BMSC injections, intramyocardial (i.m.) versus intravenous (i.v.) administration of cells. A control group was treated with i.m. injections of saline. The hourly number of supra- and ventricular premature contractions (VPCs), QT interval time and QTc time were recorded and calculated. At Day 7 after cell injections, VPCs were more frequent in the groups treated with i.m. BMSCs and i.m. saline compared with i.v. BMSCs (132 ±19; 54±14 and 34±9, respectively; P<0.01 within groups), whereas at Day 21 the number of VPCs was higher in the 2 groups treated with either i.m. or i.v. BMSCs compared with saline (96±23; 52±19 and 25±20, respectively; P<0.001 within groups). QTc time interval was prolonged during ischemia, and recovered in control and in the group treated with i.v. cells, whereas it remained longer in rabbits treated with i.m. BMSCs. These findings show that i.m. BMSC injections induced a high number of pre-arrhythmic events suggesting changes in cardiac electrophysiological properties. The i.v. administration of cells resulted in lower VPC beats and in a temporary QT prolongation. These results suggest that the combination of BMS cells and i.m. injections induced an electrical remodeling that contributed to the development of arrhythmias.

Abstract 8823: Abnormal Cardiac Innervation in Ventricular Fibrillation Patients with and Without Brugada Syndrome

Abnormal cardiac innervation in patients with ventricular fibrillation (VF) has been reported. We investigated autonomic function in 48 successfully resuscitated VF patients using heart rate variability (HRV) as measured by Holter ECG and 123 I-metaiodobenzylguanidine ( 123 I-MIBG) scintigraphy. Eight patients were excluded because of hypertrophic cardiomyopathy (N = 2), arrhythmogenic right ventricular cardiomyopathy (N = 3), catecholamine-sensitive ventricular tachycardia (N = 1), and long QT syndrome (N = 2). Patients who could not discontinue internal remedies (N = 5) were also excluded. Fifteen patients (42 ± 14 years, 15 males) were diagnosed with Brugada syndrome (BS), and the remaining 20 patients (47 ± 6 years, 8 males) were diagnosed with idiopathic VF (IVF). QTc time was longer in the IVF patients than in the BS patients (450.1 ± 10.1 ms vs. 389.4 ± 21.0 ms, P &lt; 0.05). RMS40 was lower in the BS patients than in the IVF patients (13.9 ± 2.2 mV vs. 20.9 ± 3.6 mV, P &lt; 0.05). Parameters of HRV were similar in both groups, but abnormal circadian variations of HRV were observed in 53.3% of BS patients and 13.3% of IVF patients. The washout ratio was higher in the IVF patients than in the BS patients (36.3 ± 4.3 vs. 26.0 ± 2.1). The 123 I-MIBG uptake was increased in lateral regions in BS patients. Regionally reduced 123 I-MIBG uptake was observed with many variations in all patients, but no significant difference was observed between groups. These results demonstrated impairment of sympathetic innervation or enhanced activity of the sympathetic nervous system in patients with VF, particularly indicating sympathetic hypertonia in IVF and imbalance of circadian HRV in BS. These findings may have an impact on the arrhythmogenesis of such patients.

Alterations in QTc and PR intervals in renal transplant patients receiving immunosuppressive drugs

IntroductionKidney transplantation is the treatment of choice for most patients with end-stage renal disease (ESRD). Strategies to increase donor organ availability and to prolong the transplanted kidney's survival have become...

Impact of different immunosuppressive drugs on QT interval in renal transplant patients

IntroductionKidney transplantation is the treatment of choice for most patients with end-stage renal disease (ESRD). Strategies to increase donor organ availability and to prolong the transplanted kidney's survival have become...

Diagnostic accuracy of a new detection algorithm for atrial fibrillation in cardiac telemonitoring with portable electrocardiogram devices

Background Telemedical approaches targeting cardiac outpatients try to include electrocardiogram (ECG) analysis. Increasing numbers of monitored patients require automated preanalysis of the ECG to prioritize the evaluation for the clinical professional to enable an efficient intervention. Methods ECGs were recorded from 60 patients, both with a standard 12-lead ECG and with a new handheld ECG device having dry electrodes for direct skin contact. Recordings of the handheld device were automatically analyzed by a new algorithm. The 12-lead recordings were evaluated by a blinded cardiologist and then compared to the automated analysis of the handheld ECG. Sensitivity and specificity of the algorithm for the detection of atrial fibrillation (AF) were calculated. Results A total of 60 ECG strips having 122 ± 36 beats were registered. One hundred percent of the ECG strips were sufficient for automated heart rate count; 96.6%, for automated AF analysis; and 80%, for PQ, QRS, and QTc time measurements. AF detection had a sensitivity of 92.9% and a specificity of 90.9%. There was no difference in heart rate count between automated and manual analysis (median, 71 vs 70 beats per minute; P = .51). Automated measurements of a summary complex showed no difference for PQ time (165 vs 161 milliseconds, P = .50) but overestimated QRS (119 vs 90 milliseconds, P = .001) and QTc (489 vs 417 milliseconds, P < .001) times as compared to the 12-lead recordings analyzed manually. Conclusion The new algorithm is suitable for automated preanalysis of the ECG data with regard to AF. It could be used for rapid selection of ECGs with relevant rhythm abnormalities from a large pool. Electrocardiographic data remain to be evaluated by health care professionals for exact diagnosis.

Clinical Practice Associated with a Switch from and to Ziprasidone during Routine Inpatient Treatment of Patients with Schizophrenia

Ziprasidone (ZIP) shows a low propensity for metabolic side effects but can prolong QTc time. It is unclear how these features translate into clinical reality. Charts of inpatients with schizophrenia and switched from (ZIP − , n = 27) or to ZIP (ZIP + , n = 24) were reviewed. Clinical data including documented switch reasons were anonymously analyzed. Comorbidity, body mass index (BMI) at admission, illness severity, side effects, illness duration, and length of stay were comparable in both groups. About 2/3 of ZIP+ were women (1/3 of ZIP − , P = 0.035); ZIP+ patients were younger (P = 0.017), had higher BMI values (P = 0.042), and received higher chlorpromazine equivalents before switch (P = 0.004) whereas ZIP doses were comparable (136 versus 141 mg/d). More patients in ZIP− versus ZIP+ were switched because of previous weight gain (P = 0.006) and depression (P = 0.085) whereas single reasons for ZIP− versus ZIP+ were mainly persisting positive symptoms (P = 0.089) and patients' choice (P = 0.10). The results of the naturalistic study corroborate controlled trials.

Recurrent Episodes of Stroke-Like Symptoms Due to Accidental Intoxication With Doxepin

Back to table of contents Previous article Next article LETTERFull AccessRecurrent Episodes of Stroke-Like Symptoms Due to Accidental Intoxication With DoxepinKatrin Gade,Mathias Bähr M.D.Pawel Kermer M.D.,Katrin GadeSearch for more papers by this author,Mathias Bähr M.D.Search for more papers by this authorPawel Kermer M.D.Search for more papers by this author,Published Online:1 Apr 2010https://doi.org/10.1176/jnp.2010.22.2.247.e23AboutSectionsPDF/EPUB ToolsAdd to favoritesDownload CitationsTrack Citations ShareShare onFacebookTwitterLinked InEmail To the Editor: Tricyclic antidepressants are used for treatment of mood disorders, anxiety, sleep disturbance, pain and psychosomatic symptoms. 1 Intoxication can lead to disorientation, hallucinations, unconsciousness, seizures, apnea, hypotension and conduction defects in the heart. 2 Here, we report a patient presenting repeatedly with stroke-like symptoms due to accidental doxepin intoxication underscoring the importance of a careful assessment of the patient’s drug history including hands-on examination of the actual medication. Case ReportA 64-year-old man with non-insulin-dependent diabetes mellitus was repeatedly referred to the emergency room presenting recurrent episodes of headache, dizziness, vertigo, impairment of gaze and speech, loss of balance, nausea, and muscle weakness. Neurological examination constantly revealed a somnolent patient with nystagmus, gait ataxia, dysarthria, dysmetric coordination, and general weakness without unambiguous paresis, sensory deficit, or reflex abnormalities. When the patient first presented, we suspected stroke, and he was monitored on our stroke unit for 24 hours. A peripheral vestibular disease was excluded by caloric testing. However, MRI scans showed no sign of fresh ischemia, intracerebral bleeding, or stenosis of cerebral arteries. A lumbar puncture revealed normal findings, and cardiologic examination showed no pathologies except for a patent foramen ovale without aneurysm. Since symptoms disappeared within 24 hours, the patient was diagnosed with a transitory ischemic attack and released with 100 mg/day of acetylsalicylic acid. A few days later, he returned with exactly the same symptoms, this time accompanied by mild hypoglycemia. After glucose infusion, the symptoms disappeared slowly, routine blood glucose measurements showed normal results under a reduced dose of his antidiabetic medication. Soon after being released, the patient fell into a glass door because of sudden abnormal weakness in both legs. A tentative antiepileptic treatment with levetiracetam was started suspecting epileptic seizure, although EEG and sleep deprivation EEG were normal. Unfortunately, this could not prevent reoccurrence of symptoms after hospital release. Since symptoms exclusively appeared at home and never in the hospital, we finally examined the patient’s home medication. Surprisingly, we found blisters of 100 mg doxepin tablets that had been prescribed a long time ago for sleeping disturbances and looked very similar to the patient’s antidiabetic pills. Although the patient denied doxepin intake during the last months, gas-chromatographic screening of his urine even some days after the suspected last intake revealed larger amounts of doxepin, which he obviously had taken by mistake instead of his antidiabetics.Discussion We report a case of recurrent accidental doxepin intoxication presenting with stroke-like symptoms, even though this substance was not part of the patient’s regular medication. Unexpectedly, ECG recordings never revealed extended QTc times or other signs of conduction defects in the heart. 2 Moreover, this case shows impressively that even in times of modern diagnostics, careful analysis of the patient’s drug history including hands-on examination of home medication is important and sometimes can be diagnostic. Department of Psychiatry and Psychotherapy, Medical School, University of Göttingen, Göttingen, GermanyDepartment of Neurology, Medical School, University of Göttingen, Göttingen

Cardiac findings in Behçet’s patients

Behçet's disease is a chronic multi-system inflammatory disorder and the severity and clinical manifestations of Behçet's patients may show geographic variation. We aimed to detect the cardiac findings in 30 Behçet's patients and compare them with the normal population (n = 29). We used color-doppler echocardiography and transesophageal echocardiography in combination. We calculated manually QT intervals and QT dispersion (QTd) from twelve-lead ECG recordings. There was no E/A inversion and coronary ischemia in all patients or control group. The E velocity difference between groups was not significant. The mean A velocity was significantly lower in Behçet's patients than normal group. The mean DT was 154.4 +/- 5.8 msec in Behçet's patients and 122.59 +/- 0.96 msec in control group (P < 0.0001). The mean IVRT was 75.66 +/- 1.36 msec in Behçet's patients and 69.1 +/- 0.55 msec in control group (P < 0.0001). There was no QTc time difference between the Behçet's patients and the control group. The mean QT dispersion (QTd) interval was 45.46 +/- 2.65 msec in Behçet's patients and 31.83 +/- 1.23 msec in control group (P < 0.0001). Atrial septal aneurysm, mitral valve prolapse and insufficiency, tricuspid valve insufficieny, and pulmonary hypertension frequencies in Behçet's patients were significantly higher than in the control group. We concluded that Behçet's cardiac involvement may effect cardiac structure and cause diastolic dysfunction, electrical instability and structural abnormalities. We also concluded that cardiac involvement in Behçet's disease may be specific for this geographic area.

Neutral effects of the novel analgesic tapentadol on cardiac repolarization due to mixed ion channel inhibitory activities

AbstractTapentadol is a novel analgesic with µ‐opioid receptor agonistic and norepinephrine reuptake inhibiting activities at submicromolar concentrations. Given that inhibition of cardiac potassium currents by noncardiovascular pharmaceuticals is a critical issue in drug development, the potential effects of tapentadol on myocardial repolarization were evaluated. Tapentadol concentration‐dependently inhibited hERG‐related currents in CHO cells with 250 and 750 times lower potency than haloperidol and sertindole. In electrically stimulated guinea pig papillary muscles, tapentadol at 10 and 100 µM shortened the action potential duration at 30% of repolarization (APD30) and APD90. Maximum effects (100 µM) were more pronounced on APD30 than on APD90. In contrast, the hERG inhibitor, d,l‐sotalol concentration‐dependently (1–100 nM) prolonged APD90 without affecting APD30. In isolated, perfused, spontaneously beating guinea pig hearts, volume‐conducted ECGs revealed that tapentadol reduced heart rate (HR) and prolonged uncorrected QT time, but did not affect HR‐corrected QTc time. The hERG inhibitor, dofetilide (0.01 and 0.1 µM) reduced HR and prolonged QT and QTc time. PR time was prolonged by tapentadol but not by dofetilide. Intravenous infusion of tapentadol (3, 6, 9mg/kg) in conscious dogs led to suprapharmacological plasma concentrations of up to 12 µM (2,531 ng/ml). QT time decreased in tapentadol‐treated dogs in parallel to an increase in HR, whereas HR‐corrected QTc time was not affected. In conclusion, the in vitro effects of tapentadol suggest mixed ion channel activities on potassium, calcium, and sodium channels at supra‐pharmacological concentrations. These activities may be neutralizing, resulting in lack of a net effect of tapentadol on cardiac repolarization. Drug Dev Res 1–12, 2010 © 2010 Wiley‐Liss, Inc.

An indicator of sudden cardiac death during brief coronary occlusion: electrocardiogram QT time and the role of collaterals

The coronary collateral circulation has a beneficial role regarding all-cause and cardiac mortality. Hitherto, the underlying mechanism has not been clarified. The aim of this prospective study was to assess the effect of the coronary collateral circulation on electrocardiogram (ECG) QTc time change during short-term myocardial ischaemia. A total of 150 patients (mean age 63 +/- 11 years, 38 women) were prospectively included in this study. An ECG was recorded at baseline and during a standardized 1 min coronary balloon occlusion. QT interval was measured before, during, and after balloon occlusion and was corrected for heart rate (QTc). Simultaneously obtained collateral flow index (CFI), expressing collateral flow relative to normal anterograde flow, was determined based on intracoronary pressure measurements. During occlusion of the left anterior descending coronary artery mean QTc interval increased from 422 +/- 33 to 439 +/- 36 ms (P < 0.001), left circumflex occlusion led to an increase from 414 +/- 32 to 427 +/- 27 ms (P < 0.001). QTc was not influenced by occlusion of the right coronary artery (RCA) (417 +/- 35 and 415 +/- 34 ms, respectively; P = 0.863). QTc change during occlusion of the left coronary artery was inversely correlated with CFI (R(2) = 0.122, P = 0.0002). Myocardial ischaemia leads to QT prolongation during a controlled 1 min occlusion of the left, but not the RCA. QT prolongation is inversely related to collateral function indicating a protective mechanism of human coronary collaterals against cardiac death.

Cardiac repolarization and striatal dopamine transporter function are interrelated

In Parkinson's disease, striatal dopamine transporter (DAT) binding and cardiac sympathetic function are disturbed. In addition, heart rate (HR)-corrected cardiac repolarisation time (QTc interval), which is partly under autonomic control, is prolonged. Whether there is physiological coupling between striatal DAT binding and QTc time (QTc-DAT relation) is not known. The purpose of this study is to evaluate QTc-DAT relation in healthy young adults. Thirty-five participants (18 women, age 26.4+/-1.8 years; mean+/-SD) were studied with iodine-123 labelled 2beta-carbomethoxy-3beta-(4-iodophenyl) nortropane single photon emission tomography. Signal-averaged ECG was recorded at rest from each participant. QTc interval was computed with Bazett's correction and with the approach by Karjalainen, getting QTc and QTk intervals, respectively. Mean striatal DAT binding, as (striatum-cerebellum)/cerebellum, was 2.63+/-0.31. Mean HR, QT, QTc and QTk intervals were 66+/-9 bpm, 340+/-25 ms, 354+/-18 ms and 351+/-16 ms, respectively. HR-QT correlation was -0.63, P value of less than 0.001. HR was not related to striatal DAT binding. QTc-DAT and QTk-DAT relations were significant, r = -0.50, P = 0.004 and r = -0.59, P = 0.0002, respectively. In linear regression model, striatal DAT binding explained 35% of the variance of QTk interval (95% confidence interval: -46.9 to -13.0, P = 0.0002). This study suggests significant physiological QTc-DAT relation in young healthy adults. QTc interval measurements might carry diagnostically important information in clinical conditions, which have an effect on both striatal DAT binding and cardiac sympathetic function.