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Effect of moderate potassium-elevating treatment in long QT syndrome: the TriQarr Potassium Study.
Marstrand, P, Almatlouh, K, Kanters, JK, Graff, C, Christensen, AH, Bundgaard, H, Theilade, J
Open heart. 2021;(2)
Abstract
BACKGROUND In long QT syndrome (LQTS), beta blockers prevent arrhythmias. As a supplement, means to increase potassium has been suggested. We set to investigate the effect of moderate potassium elevation on cardiac repolarisation. METHODS Patients with LQTS with a disease-causing KCNQ1 or KCNH2 variant were included. In addition to usual beta-blocker treatment, patients were prescribed (1) 50 mg spironolactone (low dose) or (2) 100 mg spironolactone and 3 g potassium chloride per day (high dose+). Electrocardiographic measures were obtained at baseline and after 7 days of treatment. RESULTS Twenty patients were enrolled (10 low dose and 10 high dose+). One patient was excluded due to severe influenza-like symptoms, and 5 of 19 patients completing the study had mild side effects. Plasma potassium in low dose did not increase in response to treatment (4.26±0.22 to 4.05±0.19 mmol/L, p=0.07). Also, no change was observed in resting QTcF (QT interval corrected using Fridericia's formula) before versus after treatment (478±7 vs 479±7 ms, p=0.9). In high dose+, potassium increased significantly from 4.08±0.29 to 4.48±0.54 mmol/L (p=0.001). However, no difference in QTcF was observed comparing before (472±8 ms) versus after (469±8 ms) (p=0.66) high dose+ treatment. No patients developed hyperkalaemia. CONCLUSION In patients with LQTS, high dose+ treatment increased plasma potassium by 0.4 mmol/L without cases of hyperkalaemia. However, the potassium increase did not shorten the QT interval and several patients had side effects. Considering the QT interval as a proxy for arrhythmic risk, our data do not support that potassium-elevating treatment has a role as antiarrhythmic prophylaxis in patients with LQTS with normal-range potassium levels. TRIAL REGISTRATION NUMBER NCT03291145.
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Relationship between dialytic parameters and reviewer confirmed arrhythmias in hemodialysis patients in the monitoring in dialysis study.
Tumlin, JA, Roy-Chaudhury, P, Koplan, BA, Costea, AI, Kher, V, Williamson, D, Pokhariyal, S, Charytan, DM, ,
BMC nephrology. 2019;(1):80
Abstract
BACKGROUND Hemodialysis patients have high rates of sudden death, but relationships between serum electrolytes, the dialysis prescription, and intra-dialytic shifts in fluid and electrolyte with arrhythmia are uncertain. METHODS We analyzed sixty-six hemodialysis patients who underwent loop recorder implantation with continuous electrocardiographic monitoring, weekly to bi-weekly testing of pre- and post-dialysis electrolytes, and detailed capture of dialysis prescription and flow sheet data for 6 months. The incidence rate ratio (IRR) of reviewer confirmed arrhythmias (RCA) during dialysis through 8 h after dialysis and associations with serum chemistries and dialytic parameters were assessed using adjusted, negative-binomial regression. RESULTS Among 66 individuals with a mean age of 56 years, 12,480 events were detected in 64 (97%) patients. RCA nadired 12-24 h after dialysis and increased during the final 12 h of the inter-dialytic interval through the first 8 h after dialysis. Higher pre-dialysis serum magnesium concentration was associated with lower incidence rate ratio for arrythmia (IRR per 1 mg/dL increase 0.49, 95% CI; 0.25, 0.94), as was dialysate calcium concentration > 2.5 mEq/L vs. 2.5 mEq/L (IRR 0.52, 95% CI: 0.39, 0.70). Neither intradialytic serum potassium nor weight change were significantly associated with RCA rate. However, there was effect modification such that arrhythmia rate was maximal with concurrently high intradialytic volume and potassium removal (Pinteraction = 0.01). CONCLUSIONS Intra and post-dialytic arrhythmias are common in hemodialysis. Additional studies designed to further elucidate whether modification of the serum magnesium concentration, dialysate calcium concentration, and the extent of intradialytic potassium and fluid removal reduces the risk of per-dialytic arrhythmia are warranted. TRIAL REGISTRATION Clinicaltrials.gov NCT01779856. Prospectively registered on January 22, 2013.
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Long-term rhythm monitoring with an implantable loop recorder in patients after the first clinical atrial fibrillation episode. Towards an individualized management.
Papakonstantinou, PE, Simantirakis, EN
Minerva cardioangiologica. 2019;(2):121-130
Abstract
Although atrial fibrillation (AF) is an arrhythmia with a variable clinical profile (symptomatic and asymptomatic episodes), the first symptomatic episode leads to its initial diagnosis in most cases. Nowadays, continuous and remote long-term cardiac rhythm monitoring is feasible by the use of implantable loop recorders. The data concerning the AF recurrences and progression after the first electrocardiographic-documented clinical AF episode demonstrates that a high percentage of patients may not suffer any other AF recurrence, or may present a low recurrence rate of the arrhythmia in the future. The AF burden may play a key role in the management of the arrhythmia as far as the decision-making for anticoagulation, rate and/or rhythm control therapy is concerned. There is evidence that a higher AF burden is associated with a higher risk of ischemic stroke. Non-vitamin K antagonists (NOACs) anticoagulants are increasingly used in the management of AF, providing a more predictable effect with rapid onset and offset of their action. The use of these agents in combination with devices that provide a continuous remote rhythm monitoring capability has encouraged anticoagulation strategies based on the AF burden. Data from tailored anticoagulation studies in AF are in favor of the long-term rhythm monitoring, ensuring a patient-centered approach with a better evaluation and more individualized management of AF, especially in patients with intermediate thromboembolic risk and high bleeding risk. Further large randomized trials are needed, not only to evaluate such strategies but also to elucidate the long-term cardiac rhythm monitoring in the AF management.
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Clinical applications of T-wave alternans assessed during exercise stress testing and ambulatory ECG monitoring.
Verrier, RL, Malik, M
Journal of electrocardiology. 2013;(6):585-90
Abstract
Analytical methods to measure T-wave alternans (TWA), a beat-to-beat fluctuation in the morphology of the ST-segment and T wave in the electrocardiogram (ECG), have been developed to address the unmet challenge of identifying individuals at increased risk for sudden cardiac death. Conventional noninvasive markers including left ventricular ejection fraction have significant limitations as many individuals who die suddenly have relatively preserved ventricular mechanical function. TWA is an attractive marker as it is closely linked to ECG heterogeneity and abnormalities in calcium handling, key factors in arrhythmogenesis. The objectives of this review are to summarize the clinical evidence supporting use of TWA in risk stratification and to discuss its current and potential applications in guiding device and medical therapy.
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Identifying drug-induced repolarization abnormalities from distinct ECG patterns in congenital long QT syndrome: a study of sotalol effects on T-wave morphology.
Graff, C, Andersen, MP, Xue, JQ, Hardahl, TB, Kanters, JK, Toft, E, Christiansen, M, Jensen, HK, Struijk, JJ
Drug safety. 2009;(7):599-611
Abstract
BACKGROUND The electrocardiographic QT interval is used to identify drugs with potential harmful effects on cardiac repolarization in drug trials, but the variability of the measurement can mask drug-induced ECG changes. The use of complementary electrocardiographic indices of abnormal repolarization is therefore warranted. Most drugs associated with risk are inhibitors of the rapidly activating delayed rectifier potassium current (I(Kr)). This current is also inhibited in the congenital type 2 form of the long QT syndrome (LQT2). It is therefore possible that electrocardiographic LQT2 patterns might be used to identify abnormal repolarization patterns induced by drugs. OBJECTIVE To develop distinct T-wave morphology parameters typical of LQT2 and investigate their use as a composite measure for identification of d,l-sotalol (sotalol)-induced changes in T-wave morphology. METHODS Three independent study groups were included: a group of 917 healthy subjects and a group of 30 LQT2 carriers were used for the development of T-wave morphology measures. The computerized measure for T-wave morphology (morphology combination score, MCS) was based on asymmetry, flatness and notching, which are typical ECG patterns in LQT2. Blinded to labels, the new morphology measures were tested in a third group of 39 healthy subjects receiving sotalol. Over 3 days the sotalol group received 0, 160 and 320 mg doses, respectively, and a 12-lead Holter ECG was recorded for 22.5 hours each day. Drug-induced prolongation of the heart rate corrected QT interval (QTcF) was compared with changes in the computerized measure for T-wave morphology. Effect sizes for QTcF and MCS were calculated at the time of maximum plasma concentrations and for maximum change from baseline. Accuracy for separating baseline from sotalol recordings was evaluated by area under the receiver operating characteristic curves (AUCs) using all recordings from the time immediately post-dose to maximum change. RESULTS MCS separated baseline recordings from sotalol treatment with higher accuracy than QTcF for the 160 mg dose: (AUC) 84% versus 72% and for the 320 mg dose: (AUC) 94% versus 87%, p < 0.001. At maximum serum-plasma concentrations and at maximum individual change from baseline, the effect sizes for QTcF were less than half the effect sizes for MCS, p < 0.001. Effect sizes at peak changes of the mean were up to 3-fold higher for MCS compared with QTcF, p < 0.001. In subjects receiving sotalol, T-wave morphology reached similarity to LQT2, whereas QTcF did not. CONCLUSION Distinct ECG patterns in LQT2 carriers effectively quantified repolarization changes induced by sotalol. Further studies are needed to validate whether this measure has general validity for the identification of drug-induced disturbed repolarization.
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Effect of oral L-type calcium channel blocker on repetitive paroxysmal atrial fibrillation: spectral analysis of fibrillation waves in the Holter monitoring.
Niwano, S, Fukaya, H, Sasaki, T, Hatakeyama, Y, Fujiki, A, Izumi, T
Europace : European pacing, arrhythmias, and cardiac electrophysiology : journal of the working groups on cardiac pacing, arrhythmias, and cardiac cellular electrophysiology of the European Society of Cardiology. 2007;(12):1209-15
Abstract
AIMS: The electrical remodelling is considered to play a role in promoting arrhythmogenic substrate of atrial fibrillation (AF), and intracellular calcium overload may play a key role, especially in its early phase. The effect of oral verapamil on repetitive paroxysmal AF (PAF) was evaluated in clinical cases. METHODS AND RESULTS Thirty-five patients with repetitive PAF (total PAF duration >2/24 h) were divided into two groups with and without verapamil administration (240 mg/day) and they were followed-up for 12 months. Before and after the follow-up period, 24 h Holter ECG was recorded. In each Holter recording, total PAF duration and the longest PAF duration was evaluated and spectral analysis was performed for fibrillation waves in PAF episodes to evaluate the fibrillatory frequency. Total PAF duration was prolonged by 45 +/- 79 min in the control group (n = 18) whereas shortened by 25 +/- 55 min in the verapamil group (n = 17, P = 0.005). The fibrillatory frequency was increased from 5.66 +/- 1.05 to 6.73 +/- 1.02 Hz in the control group and was unchanged in the verapamil group. There was inverse relationship between Deltatotal PAF duration and Deltafibrillatory frequency (P = 0.0002). CONCLUSION Verapamil prevented the increase in fibrillatory frequency in PAF patients in relatively long-term observation. Verapamil might be effective for prevention of the electrophysiological change and increase in PAF episodes at least in specific type of PAF cases.
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Dynamic analysis of the QT interval in long QT1 syndrome patients with a normal phenotype.
Lande, G, Kyndt, F, Baró, I, Chabannes, D, Boisseau, P, Pony, JC, Escande, D, Le Marec, H
European heart journal. 2001;(5):410-22
Abstract
AIMS: In families with the long QT syndrome penetrance may be low: up to 70% of gene carriers may have a normal QTc interval. These patients require therapy, similar to that in those with longer QTc intervals, but identifying them, using molecular analysis, is difficult to apply on a large scale. A large French family affected by the long QT1 syndrome was followed-up over a 25-year period. In adult males but not in females, the QTc interval normalized after puberty. We aimed to find clinical criteria, based on ambulatory ECG recordings so that we could improve diagnosis in affected members with a normal QTc. METHODS AND RESULTS Linkage analysis and direct sequencing were an indicator of the long QT1 gene in our family. Reverse transcription-polymerase chain reaction analysis demonstrated abnormal transcripts in lymphocytes from silent gene carriers. The functional profile of mutated protein isoforms was investigated using the patch-clamp technique. Dynamic analysis of ventricular depolarization was conducted using Holter recordings in patients, and in sex- and age-matched controls. Circadian variations of the QTc interval and the QT/RR relationship were assessed. Sensitivity, specificity, and predictive values were evaluated for proposed clinical criteria. We found that dynamic analysis of the QT interval permitted individual diagnosis in mutation carriers even when the QTc interval was normal (adult males). CONCLUSION Dynamic analysis of the QT interval is of diagnostic value in the long QT1 syndrome in patients with a normal phenotype. Clinical implications include improvement in screening and patient management.
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[Effect of probucol on cardiac electrophysiology in anginal patients with hyperlipidemia and diabetes mellitus type II].
Anikin, VV, Savin, VV, Lupanov, VP, Razygraev, RA
Terapevticheskii arkhiv. 2000;(8):28-30
Abstract
AIM: To investigate effects of a hypolipidemic drug with antioxidant action probucol on electrophysiological parameters of the heart in patients with ischemic heart disease (IHD), stable angina (SA), hyperlipoproteinemia (HLP) and diabetes mellitus (DM) type II. MATERIAL AND METHODS The trial entered 48 IHD patients (11 males and 37 females) aged 47-73 years with SA functional class II and III (39.4 and 60.6%, respectively), secondary HLP (mean group total cholesterol 6.5 +/- 0.17 mmol/l), DM type II (mean fast glucose 7.7 +/- 1.8 mmol/l) and obesity (mean body mass index 29.7 +/- 2.2 kg/m2). Transesophageal pacing of the left ventricle was conducted in all the patients before probucol treatment and 18 hours, 1 month and 3 months after it. RESULTS Probucol (a single dose 500 mg) significantly reduced the time of recovery of sinus node function. Three months of probucol administration in a dose 1000 mg/day enhanced pacemaker activity of the sinus node. CONCLUSION In addition to a beneficial effect on lipid metabolism (a decrease of total cholesterol by 13.4%, LDLP cholesterol by 15.2%, triglycerides by 15.8%), probucol enhanced pacemaker activity of the sinus node. This makes it perspective in patients with sinus node dysfunction. Caution is necessary in prescribing probucol to patients with supraventricular tachycardia caused by re-entry mechanism.