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1
Licata, Anthony, and Alistair Savage. "Hecke algebras, finite general linear groups, and Heisenberg categorification." Quantum Topology 4, no. 2 (2013): 125–85. http://dx.doi.org/10.4171/qt/37.
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Séguéla, Pierre-Emmanuel, Jean-Christophe Rozé, and Véronique Gournay. "Evolution of the QT interval in premature infants: a preliminary study." Cardiology in the Young 22, no. 4 (December 19, 2011): 430–35. http://dx.doi.org/10.1017/s1047951111001958.
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AbstractBackgroundThe association between long QT interval and sudden infant death syndrome has been clearly established. Several studies have been conducted to determine the evolution of the QT interval in childhood from birth, but only in full-term newborns. However, data on the QT interval in pre-term infants are extremely scarce. The objective was to describe the development of the QT interval in premature infants.Material and methodsIn a prospective monocentric study in a neonatal intensive care unit, pre-term newborns born before 37 weeks of gestation without congenital heart disease, family history of long QT, unstable haemodynamic status, or administration of drugs inducing QT interval prolongation were included with parental consent. An electrocardiogram was recorded in similar conditions weekly until discharge in each child. The corrected QT was calculated with Bazett's formula.ResultsIn all, 309 echocardiograms were recorded in 87 children, with gestational age ranging from 24–36 weeks. QT first increased after birth in very premature infants – less than 30 weeks of gestation – and then started to decrease, whereas it only decreased in more mature infants. When plotted against postmenstrual age, QT first increased, and then decreased after 32 weeks.DiscussionOur data suggest that the QT interval varies with postmenstrual age in very premature infants, reaching a peak at 32 weeks. These developmental changes may induce specific vulnerability to QT-lengthening medications in premature infants. This study underlines the need for specific pharmacological studies in this population.
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Orosz, Andrea, István Baczkó, Viktória Nagy, Henriette Gavallér, Miklós Csanády, Tamás Forster, Julius Gy Papp, András Varró, Csaba Lengyel, and Róbert Sepp. "Short-term beat-to-beat variability of the QT interval is increased and correlates with parameters of left ventricular hypertrophy in patients with hypertrophic cardiomyopathy." Canadian Journal of Physiology and Pharmacology 93, no. 9 (September 2015): 765–72. http://dx.doi.org/10.1139/cjpp-2014-0526.
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Stratification models for the prediction of sudden cardiac death (SCD) are inappropriate in patients with hypertrophic cardiomyopathy (HCM). We investigated conventional electrocardiogram (ECG) repolarization parameters and the beat-to-beat short-term QT interval variability (QT-STV), a new parameter of proarrhythmic risk, in 37 patients with HCM (21 males, average age 48 ± 15 years). Resting ECGs were recorded for 5 min and the frequency corrected QT interval (QTc), QT dispersion (QTd), beat-to-beat short-term variability of QT interval (QT-STV), and the duration of terminal part of T waves (Tpeak–Tend) were calculated. While all repolarization parameters were significantly increased in patients with HCM compared with the controls (QTc, 488 ± 61 vs. 434 ± 23 ms, p < 0.0001; QT-STV, 4.5 ± 2 vs. 3.2 ± 1 ms, p = 0.0002; Tpeak–Tend duration, 107 ± 27 vs. 91 ± 10 ms, p = 0.0015; QTd, 47 ± 17 vs. 34 ± 9 ms, p = 0.0002), QT-STV had the highest relative increase (+41%). QT-STV also showed the best correlation with indices of left ventricular (LV) hypertrophy, i.e., maximal LV wall thickness normalized for body surface area (BSA; r = 0.461, p = 0.004) or LV mass (determined by cardiac magnetic resonance imaging) normalized for BSA (r = 0.455, p = 0.015). In summary, beat-to-beat QT-STV showed the most marked increase in patients with HCM and may represent a novel marker that merits further testing for increased SCD risk in HCM.
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Olson, Stephen C., Ann Marie Horvath, Barbara M. Michniewicz, Allen J. Sedman, Wayne A. Colburn, Peter G. Welling, and Stephen C. Olson. "The Clinical Pharmacokinetics of Quinapril." Angiology 40, no. 4_part_2 (April 1989): 351–59. http://dx.doi.org/10.1177/000331978904000404.
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Quinapril (Q) and quinaprilat (QT) pharmacokinetics are dose pro portional following single oral 2.5- to 80-mg Q doses. Q absorption and hy drolysis to QT is rapid with peak Q and QT concentrations occurring one and two hours postdose, respectively. Peak plasma QT concentrations were approximately fourfold higher than those of Q (923 vs 207 ng/mL follow ing 40-mg Q). Dose-proportional QT area under the curve and dose-inde pendent percent of dose excreted in urine as QT demonstrate that the ex tent of Q conversion to QT is con stant over the dose range studied. Q and QT were eliminated from plasma with apparent half-lives of 0.8 and 1.9 hours and apparent plasma clear ances of 1,850 and 220 mL/min, re spectively, over the 2.5- to 80-mg dose range. Following oral 14C-Q, 61% and 37% of radiolabel was recovered in urine and feces, respectively. Q plus QT accounted for 46% of radioactiv ity circulating in plasma and 56% of that excreted in urine. Metabolism to compounds other than QT is not extensive. Two diketo piperazine metabolites of Q have been identified in plasma and urine, with approximately 6% of an admin istered dose excreted in urine as each of these metabolites. Peak plasma concentrations of these metabolites are similar to that of Q, and each is eliminated rapidly with a half-life of approximately one hour. Urinary ex cretion profiles indicate the presence of other minor metabolites. In summary, the absorption of Q and conversion to QT is rapid and dose-proportional, subsequent clear ance of both Q and QT is independ ent of dose, and metabolism to compounds other than QT is not ex tensive.
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Arpaci, Dilek, Mustafa Volkan Demir, Tayfun Garip, and Ali Tamer. "A Case of QT Prolongation Associated with Panhypopituitarism." Case Reports in Endocrinology 2013 (2013): 1–4. http://dx.doi.org/10.1155/2013/989745.
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We describe a 37-year-old patient with panhypopituitarism who experienced symptoms and signs of hormonal insufficiency and QT prolongation on electrocardiogram without electrolyte disturbances. After hormonal (steroidal and thyroid) replacement therapy electrocardiographic findings were normalized. Hormonal disorders should be considered as a cause of long QT intervals which may lead to torsade de pointes, even if plasma electrolyte levels are normal, because life-threatening arrhythmia is treatable by supplementation of the hormone that is lacking.
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SOYSAL GÜNDÜZ, Özgül, and Kezban ARMAGAN. "Increased QT dispersion and related factors in patients with systemic sclerosis." Anatolian Current Medical Journal 4, no. 4 (October 22, 2022): 368–73. http://dx.doi.org/10.38053/acmj.1132856.
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Introduction: Cardiac arrhythmias and sudden death may occur as a result of ventricular myocardial fibrosis or ischemia in patients with systemic sclerosis (SSc). QT prolongation and QT dispersion, which facilitate the development of ventricular fibrillation, are important cardiac problems associated with increased mortality. In this study, we aimed to investigate the prevalence of corrected QT dispersion (cQTD) and related factors in our patients with systemic sclerosis compared to healthy controls.
Material and Method: The 12-lead electrocardiograms with a rate of 25 mm/s of patients with no previous history of cardiovascular disease and controls were analyzed. cQTD was defined as the difference between the maximum QT interval and the minimum QT interval. Nailfold capillaroscopy examination was performed. Disease activity was evaluated using revised European Scleroderma Study Group activity index.
Results: Forty-nine SSc patients (45 females, mean age 53.26±10.63 years, and disease duration 8.0 (1-25) years) and 41 controls (37 females, mean age 49.29±8.02 years) were included. While the frequency of smoking was significantly higher in controls (p=0.025), erythrocyte sedimentation rate was higher in patients (p
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Shea, Kevin G., Jessica F. Burlile, Connor G. Richmond, Henry B. Ellis, Philip L. Wilson, Peter D. Fabricant, Stephanie Mayer, et al. "Quadriceps Tendon Graft Anatomy in the Skeletally Immature Patient." Orthopaedic Journal of Sports Medicine 7, no. 7 (July 2019): 232596711985657. http://dx.doi.org/10.1177/2325967119856578.
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Background:The quadriceps tendon (QT) is increasingly considered for primary and revision anterior cruciate ligament reconstruction in skeletally immature patients, as it may be harvested as a purely soft tissue graft with considerable tissue volume. Because of distinct rectus tendon (RT) separation from the QT complex, the potential for RT retraction exists and could lead to QT weakness after QT graft harvest.Purpose:To describe the anatomy of the pediatric QT and clarify decussation of the RT and QT to avoid the risk of delayed RT retraction and QT weakness after QT graft harvest.Study Design:Descriptive epidemiology study.Methods:Nine cadaveric knee specimens (aged 4-11 years) underwent gross dissection. Coronal-plane width and depth of the QT were measured at intervals proximal to the superior pole of the patella at distances of 0.0, 0.5, 1.0, and 1.5 times the length of the patella. The distance was measured from the superior patellar pole to the point of RT separation from the remainder of the deeper/posterior QT.Results:The median patellar length was 28 mm (interquartile range, 26-37 mm). The coronal-plane width of the QT was larger superficially/anteriorly when closest to the patella but wider when measured deeper/posteriorly as the tendon extended proximally. The median distance between the superior pole of the patella and RT separation from the QT was 0.95 times the patellar length. The distance to widening of the deeper/posterior aspect of the QT was 1.14 times the patellar length proximal to the patella.Conclusion:The RT begins a distinct separation from the QT above the superior pole of the patella at a median of 0.95 times the patellar length in skeletally immature specimens. The deeper/posterior aspect of the QT begins to increase in coronal-plane width proximally after a distance of 1.14 times the patellar length above the knee, while the superficial/anterior aspect of the tendon continues to narrow. Awareness of the separation of the RT from the QT, and the coronal-plane width variation aspects of the QT proximally, is important for surgeons utilizing the QT as a graft to avoid inadvertent release of the RT from the rest of the QT complex.
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Määttänen, Ilmari, Niklas Ravaja, Pentti Henttonen, Sampsa Puttonen, Kristian Paavonen, Heikki Swan, and Taina Hintsa. "Type 1 long QT syndrome and psychological stress in a laboratory setting." Journal of Health Psychology 25, no. 9 (January 22, 2018): 1213–21. http://dx.doi.org/10.1177/1359105317751617.
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Trait-like sensitivity to stress in long QT syndrome patients has been documented previously. In addition, mental stress has been associated with symptomatic status of long QT syndrome. We examined whether the symptomatic type 1 long QT syndrome patients would be more sensitive to mental stress compared to asymptomatic patients and whether there would be differences in task-related physiological stress reactions between type 1 long QT syndrome patients and healthy individuals. The study population consisted of 21 symptomatic and 23 asymptomatic molecularly defined KCNQ1 mutation carriers, their 32 non-carrier relatives and 46 non-related healthy controls, with mean ages of 37, 39, 35 and 23 years, respectively. Electrocardiography was utilised to calculate inter-beat interval and high frequency and low frequency heart rate variability. Blood pressure was measured and mean arterial pressure and pulse pressure were calculated. Stress was induced using three different tasks: mental arithmetic, reaction time and public speech. Stress responses of symptomatic and asymptomatic type 1 long QT syndrome patients were not statistically different in any of the stress tasks. Short-term physiological stress reactivity of symptomatic type 1 long QT syndrome patients appears to be normal and does not enhance the risk assessment of asymptomatic mutation carriers.
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Brady, William, Daniel DeBehnke, Dennis Laundrie, and Jeffrey A. Skiles. "21. Prolonged QT Intervals in Patients with Out-of-Hospital Ventricular Tachycardia Cardiac Arrest." Prehospital and Disaster Medicine 11, S2 (September 1996): S40. http://dx.doi.org/10.1017/s1049023x00045854.
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Objective: To determine the prevalence and outcome of out-of-hospital ventricular tachycardia (VT) cardiac arrest with a prolonged QT interval and to identify the subset with torsades de pointes (TdP).Methods: Design: Retrospective review. Setting: Fire department-based paramedic system. Participants: Non-traumatic VT cardiac arrest (1/91-12/94) with a supraventricular perfusing rhythm (SVPR) and a measurable QT interval. Interventions: QT interval was measured from a SVPR and corrected QT interval (QTc) was calculated (prolonged if ≥0.45 sec). VT was classified as polymorphic or monomorphic.Results: 190 patients met inclusion criteria. 51% of patients had a prolonged QTc (PQTc). The overall hospital discharge rate was 28.4%. No difference with respect to paramedic-witnessed arrests in each QTc group was found (25.8% normal QTc [NQTc] vs. 27.8% PQTc; p = 0.752). Patients with PQTc were less likely to be discharged from the hospital (19.6% vs. 37.6%; p = 0.01). Patients with PQTc were not more likely to have PVT (37% vs. 40%; p = 0.705). 16 (8.4%) patients had TdP. 27.8% of TdP and 26.8% of non-TdP patients were discharged (p = 0.912).
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Rhatomy, Sholahuddin, Roy Lisang, Noha Roshadiansyah Soekarno, and Bambang Kisworo. "Evaluation of Quadriceps Strength Post-medial Patellofemoral Ligament Reconstruction Using Quadriceps Tendon Autografts." Open Access Macedonian Journal of Medical Sciences 8, A (December 20, 2020): 943–46. http://dx.doi.org/10.3889/oamjms.2020.5551.
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BACKGROUND: Medial patellofemoral ligament (MPFL) reconstruction using quadriceps tendon (QT) grafts provides favorable results with minimal complications and can be performed in patients with open epiphyseal plates. Following MPFL reconstruction using QT grafts, the outcomes have been evaluated, but the residual quadriceps strength (QS) has never been evaluated.
AIM: We analyzed the knee’s range of motion (ROM), thigh circumference (TC), and QS at donor leg sites compared with those at contralateral healthy sites after MPFL reconstruction. The hypothesis was that there is no morbidity at donor sites.
MATERIALS AND METHODS: Patients who underwent MPFL reconstruction using QT autografts between January and December 2017 were recruited. The ROM, TC, and QS were measured 6 months postoperatively.
RESULTS: Twenty-one patients (8 men, 14 women; mean age, 28.40 ± 10.78 years [range, 16–45]) were included in the study. The TCs at the donor and contralateral sites (medians: 37 and 37.5 cm, respectively) showed no significant difference (p = 0.64). QS measurements showed means of 182 ± 4.6 N and 190 ± 4.7 N at the donor and contralateral sites, respectively (p = 0.376). There were no ROM deficits.
CONCLUSIONS: The ROM, TC, and QS at donor sites were similar to those at contralateral sites. The QT is a suitable graft for MPFL reconstruction.
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Choueiri, Toni K., Esteban Walker, Rachid C. Baz, Rony M. Abou-Jawde, Snehal G. Thakkar, Bridget McGowan, Megan Kelly, Steven Andresen, and Mohamad Hussein. "Aggressive Electrolytes Replacement in Multiple Myeloma (MM) Patients Receiving Arsenic Trioxide (ATO) Containing Regimens Alleviates the Need for Frequent Electrocardiogram (ECG) Monitoring." Blood 106, no. 11 (November 16, 2005): 5155. http://dx.doi.org/10.1182/blood.v106.11.5155.5155.
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Abstract Background: Arsenic trioxide (ATO) has shown activity in relapsed/refractory multiple myeloma (MM). An uncommon but life-threatening side effect of ATO is arrhythmia such as torsade de pointes (TdP), especially when QT or QTc (heart-rate corrected) intervals >500 milliseconds (ms). We evaluated the incidence and predictors of QT and QTc prolongation in MM patients treated with ATO. Methods: We reviewed prospectively collected demographic, laboratory and 766 weekly-ECG data on 48 patients treated in phase II trials with ATO. Patients received a median of 1.7 cycles (range 1–8) of 0.1–0.25 mg/Kg of IV ATO. Cycles consisted of 12 weeks of ATO (5-days/week for 1 week, then twice weekly for 11 weeks). Electrolytes were aggressively repleted to keep serum electrolytes as follows: K > 4 mEq/L, Mg > 2 mg/dL and Ca > 8.5 mg/dL. Endpoints included number of patients with QT and QTc prolongation (> 450 ms in males and > 470 ms in females), percentage of QT and QTc > 500 ms, and arrhythmia incidence. Predictors for QT and QTc prolongation were analyzed using a logistic regression model. Results: Median patient age was 67.4 years. 85% were Caucasians, 64 % were males, and 37% achieved a response to ATO (CR or PR). Throughout the study, median values for K, Mg, Ca were 4.3 (4.0, 4.5), 2.1 (1.9, 2.2), and 9.1 (8.6, 9.4), respectively. Prolonged QT and QTc intervals at any time during the study occurred in 6/48 patients (12.5%) and in 25/48 patients (52%), respectively. ATO therapy was held based on ECG changes in 2 patients. One of whom had both QT and QTc > 500 ms and was found to be on a phenothiazine derivative; the other patient had only QTc > 500 ms and was found to have severe hypomagnesemia and hypocalcemia. After discontinuing the offensive drug and correcting electrolytes, therapy was restarted without any further QT or QTc prolongation. Overall, QT and QTc intervals returned to baseline with subsequent doses indicating the absence of a cumulative dose-effect. The factors influencing QT and QTc considered in the statistical analyses were age, race, gender, and response. In univariate and multivariate analyses, the only variable associated with QT and QTc prolongation was male gender (p<0.01). No TdP or any other ATO-related arrhythmia occurred. Conclusion: ATO can result in prolongation of QT and to a higher degree QTc interval. QT and QTc are rarely prolonged > 500 ms. Males were more likely to develop QT and QTc prolongation. With repeated administration, a dose-cumulative effect does not seem to further prolong QT or QTc. ATO can be safely administered to patients with MM when electrolytes and concomitant medications are appropriately managed. Decisions based on ECG occurred in two patients during the first 12 weeks of therapy, utilizing 2/766 ECG’s (0.003%). Weekly ECG’s may therefore not be warranted in this clinical setting.
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VandenBerg, Curtis D., Mia J. Katzel, Veronica Beltran, Adriana S. Conrad-Forrest, and Tishya A. L. Wren. "EFFECT OF AUTOGRAFT TYPE ON RECOVERY OF KNEE EXTENSOR MECHANISM FUNCTION FOLLOWING ANTERIOR CRUCIATE LIGAMENT RECONSTRUCTION." Orthopaedic Journal of Sports Medicine 9, no. 7_suppl3 (July 1, 2021): 2325967121S0009. http://dx.doi.org/10.1177/2325967121s00094.
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Background: While multiple studies have shown clear benefits of autograft over allograft for anterior cruciate ligament reconstruction (ACLR) in young athletes, disagreement remains regarding the optimal autograft choice. Recovery from ACLR may be influenced by autograft type, which can include iliotibial band (IT), hamstring tendon (HT), quadriceps tendon (QT), or patellar tendon (PT) depending on skeletal maturity and surgeon preference. Hypothesis/Purpose: This study compared knee joint function among pediatric athletes with different types of ACLR autografts. We hypothesized that knee extensor function would recover faster for graft types that did not disrupt the knee extensor mechanism (i.e., IT and HT vs. PT and QT). Methods: This retrospective study examined 138 pediatric athletes (73 female; mean age 15.5, SD 2.2, range 8-21 years) who had undergone sports biomechanical testing in our motion analysis laboratory following recent unilateral ACLR (mean 7.7, range 3-18 months post-surgery). All reconstructions used autografts including 20 IT, 26 HT, 37 QT, and 55 PT. Lower extremity sagittal plane kinematics and kinetics were measured during vertical drop jump landing (41 cm height) and 45° cutting. Maximum knee flexion angles, internal knee extensor moments, and energy absorption during the landing phase (initial contact to peak knee flexion) of each movement were compared among graft types and sides (ACLR vs. contralateral) using linear mixed models with sex, age, and time since surgery as covariates. Results: Knee flexion was significantly lower on the operated vs. contralateral side for HT, QT, and PT during drop jump and for QT and PT during cutting (p<0.001). All graft types exhibited lower knee extensor moments and energy absorption on the operated side (p<0.05). This asymmetry was most pronounced for QT and PT and least pronounced for IT (Figure 1.1). Loading on the operated limb decreased from IT to HT to QT and PT, while loading on the contralateral limb increased similarly. Asymmetry of kinetics was significantly lower for IT compared with both QT and PT during both movements (p<0.01). Similar patterns were observed for HT but were not always statistically significant. No differences in asymmetry were observed between IT and HT or between QT and PT. Conclusion: Young athletes with IT and HT autografts exhibit greater engagement of the knee extensors during dynamic loading than peers with PT or QT autografts in the 18 months following ACLR. This may be due to extensor mechanism donor site morbidity associated with PT and QT grafts. Tables/Figures: [Figure: see text]
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Asefa, G., and M. Beriso. "Evaluation of black cumin genotypes for yield and yield related parameters in bale mid altitude, southeastern Ethiopia." International Journal of Agricultural Research, Innovation and Technology 10, no. 2 (January 21, 2021): 35–37. http://dx.doi.org/10.3329/ijarit.v10i2.51574.
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Fourteen black cumin genotypes were evaluated against standard checks for two consecutive years during 2018 to 2019 at Sinana, Goro and Gindhir to investigate high yielder and stable black cumin varieties. The mean total seed yield of genotypes across environment ranged from 24.54 to 16.07 Qt ha-1. The highest total seed yield was recorded from genotypes 242826-2 followed by 242826-2 (24.54 and 23.32 Qt ha-1) while the lowest total seed yield was obtained from local checks. These two genotypes have yield advantage of 22.41 and 14.96% over standard check Derbera. Based on their performance across location over standard checks these two genotypes will be promoted for variety verification for Bale mid altitude and similar agro ecologies.
Int. J. Agril. Res. Innov. Tech. 10(2): 35-37, December 2020
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Fialová, Kateřina, Jiří Blahák, Marek Motola, Jiří Jarkovský, Jan Mužík, and Marie Nováková. "Effect of perphenazine on electrogram of rat isolated heart." Acta Veterinaria Brno 80, no. 1 (2011): 87–92. http://dx.doi.org/10.2754/avb201180010087.
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The aim of this study was to clarify whether administration of antipsychotic perphenazine contributes to the electrophysiological changes of the isolated heart. Fourteen adult male Wistar rats were divided into two groups. Langendorff hearts were perfused with Krebs-Henseleit solution at constant pressure (85 mmHg) and 37 °C (CaCl2, 1.2 mM). The electrogram was recorded by touch-free method. The hearts of the first group were exposed to 3.10-5 M perphenazine, the hearts of the second group to 3.10-8 M perphenazine. The incidence of arrhythmias and the heart rate and QT interval changes were studied on electrogram during 30 min periods of control, the first perphenazine administration, washout, and the second drug administration. Perphenazine administration significantly prolonged QT (p < 0.001) and QTc (p < 0.05) in group 1. In group 2, QT and QTc prolongation was less pronounced (p < 0.05). A number of arrhythmias appeared, from single premature ventricular complexes to more severe ones in both groups. The heart rate changes were non-significant. We conclude that although phenothiazines are still medicaments of choice in certain psychoses, their cardiovascular side effects should be always taken in consideration.
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Blich, Miry, Edna Efrati, Ibrahim Marai, Mahmoud Suleiman, Lior Gepstein, and Monther Boulous. "Novel Clinical Manifestation of the Known SCN5A D1790G Mutation." Cardiology 132, no. 4 (2015): 228–32. http://dx.doi.org/10.1159/000437089.
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The D1790G mutation was found in all 24 patients of an extended long QT family but not in 200 chromosomes carried by healthy individuals. We describe a 37-year-old man presenting with a typical spontaneous type 1 Brugada pattern who in electrophysiological testing had easily inducible ventricular fibrillation. At the age of 47 years he had an atrial ventricular type 2 block documented by an exercise test and a Holter monitor. Genetic analysis revealed a known D1790G mutation in the gene encoding of the sodium channel (SCN5A) that until now has been associated only with the long QT phenotype. Although this mutation has not been associated with a reduction of sodium channel expression, we hypothesize that sodium currents are further diminished due to the 20-mV shift of the steady-state inactivation curve, and this could contribute to the Brugada phenotype. This case is important as it allows a better understanding of the underlying molecular mechanisms of Brugada syndrome. Moreover, this observation raises concern about the safety of class IC drug therapy in long QT type 3 patients and quinidine therapy in Brugada patients, and emphasizes the importance of a thorough clinical and genetic evaluation.
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Valdivieso Lama, Natalia, Carlos Barrionuevo Cornejo, Judith Vidal Ayllon, Luis Casanova Marquez, Claudio Flores Flores, Lourdes López Chavez, Cindy Alcarraz Molina, Rossana Ruiz Mendoza, and Shirley Quintana Truyenque. "Características clínicas y pronóstico de los pacientes con linfoma leucemia de células t del adulto." Oncología (Ecuador) 32, no. 3 (December 7, 2022): 320–33. http://dx.doi.org/10.33821/657.
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Introducción: El objetivo del presente estudio fue determinar las características clínicas y pronóstico de los pacientes con Leucemia/Linfoma de Células T del Adulto (ATL) en el Instituto Nacional de Enfermedades Neoplásicas (INEN) de Perú. Metodología: Se realizó un estudio transversal, que incluyó por Se revisaron 188 historias clínicas y estudio patológico de pacientes con infección por HTLV-1 diagnosticados en el INEN durante 10 años, de quienes 150 tuvieron ATL. Resultados: 62% de los pacientes tuvieron el subtipo ATL linfoma, 37% subtipo agudo y 1% crónico. La mediana de edad fue 53 años (20-89); 51% fueron mujeres. Dentro de las características clínicas: ECOG > o = 2 (56%); estadio clínico III-IV (80%), síntomas B (58%); incremento de la deshidrogenasa láctica, LDH, (74%); leucocitosis (50%); hipercalcemia (46%) y anemia (36%). 122 pacientes (81,3%) recibieron tratamiento, 79% con quimioterapia (QT) y 4,6% radioterapia complementaria (RT); CHOP fue el esquema de QT más frecuente (89%). De los pacientes con QT tuvieron 18% RC, 32% RP, 7% EE y 13% PE. Conclusión: En este reporte en pacientes con ATL, la forma linfoma es el subtipo más frecuente, existe alta prevalencia de inmunofenotipo atípico y pobre respuesta al CHOP.
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Carlile, P. V., S. F. Hagan, and B. A. Gray. "Perfusion distribution and lung thermal volume in canine hydrochloric acid aspiration." Journal of Applied Physiology 65, no. 2 (August 1, 1988): 750–59. http://dx.doi.org/10.1152/jappl.1988.65.2.750.
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We investigated the effects of a brief period of positive end-expiratory pressure (PEEP) ventilation or nitroglycerin (NTG) infusion on the distribution of pulmonary blood flow and extravascular thermal volume (ETV) in anesthetized dogs with unilateral HCl lung injury. ETV was determined by the thermal dye technique by use of a monoexponential extrapolation to exclude recirculating indicator, and regional blood flow was determined by a particle distribution technique (radiolabeled plastic microspheres). The lungs were weighted after the animals were killed, and extravascular lung mass (ELM) was determined with the use of hemoglobin to correct for trapped lung blood. Measurements were obtained before instillation of HCl into the right lung and repeated 3 h later before, during, and after PEEP ventilation or NTG infusion. Fractional perfusion of the severely injured portion of the right lung (Qinj/QT) fell from 44.3 +/- 11.1% at base line to 27.8 +/- 15.4% after the onset of lung injury. PEEP produced an acute reversible increase in ETV (63 +/- 37% over average of pre- and post-PEEP values), and the changes in ETV were closely correlated with changes in Qinj/QT (r = 0.91). NTG infusion produced insignificant increases in ETV (14 +/- 10% over average of pre- and postinfusion values) and Qinj/QT (59 +/- 35%), but the changes in ETV and Qinj/QT were strongly correlated (r = 0.92). The fraction of extravascular lung mass detected by the thermodilution measurement averaged 0.44 (range 0.24-0.77).(ABSTRACT TRUNCATED AT 250 WORDS)
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Gervais, Anne-Sophie, Adrien Flahault, Chan Tevy, Camille Bastien-Tardif, Amy Al-Simaani, Anik Cloutier, Luu Thuy Mai, Abadir Sylvia, and Nuyt Anne-Monique. "97 Electrocardiographic features at rest and during exercise in young adults born preterm below 30 weeks of gestation." Paediatrics & Child Health 25, Supplement_2 (August 2020): e40-e41. http://dx.doi.org/10.1093/pch/pxaa068.096.
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Abstract Introduction/Background Preterm birth has adverse consequences on the cardiovascular system. Whether premature birth is associated with conduction and repolarisation abnormalities past childhood and into adulthood still needs to be demonstrated. An exercise test could reveal such abnormalities. Objectives We aimed to assess electrocardiographic changes, particularly corrected QT (QTc) prolongation, in a cohort of young adults born preterm, at rest and during exercise. Design/Methods We analysed the ECG of young adults (23.9±3.1 years) born term (≥37 weeks, n=53) and preterm (<30 weeks, n=49) at rest, peak exercise and 3 minutes into recovery during an exercise test on a cycle ergometer. We measured PR, QRS and QT intervals, calculated the QTc, and determined blood calcium, magnesium, potassium and fasting glucose. Results Mean gestational age was 39.7±1.1 and 27.3±1.3 weeks for the term and the preterm groups, respectively. Apart from an increased heart rate at rest in individuals born preterm, no significant difference was found between both groups for any other ECG parameters at rest (Table 1). None of the participants had a severely prolonged QTc (>500ms) at rest; exercise revealed severely prolonged QTc in two participants including one in the preterm group. The use of QT-prolonging medications did not influence ECG parameters in either groups. Conclusion We observed no significant difference in electrocardiographic measurements between young adults born preterm and term. Current results do not support avoidance of QT-prolonging medications in individuals born preterm.
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Schmücker, Malte, Jørgen Haraszuk, Per Hölmich, and Kristoffer W. Barfod. "Graft Failure, Revision ACLR, and Reoperation Rates After ACLR With Quadriceps Tendon Versus Hamstring Tendon Autografts: A Registry Study With Review of 475 Patients." American Journal of Sports Medicine 49, no. 8 (June 8, 2021): 2136–43. http://dx.doi.org/10.1177/03635465211015172.
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Background: It has been indicated that anterior cruciate ligament reconstruction (ACLR) with a quadriceps tendon (QT) graft has a higher risk of revision compared with ACLR performed with a hamstring tendon (HT) graft. Purpose/Hypothesis: To investigate whether ACLR with QT graft had a higher risk of graft failure, revision ACLR, or reoperation compared with HT graft in a high-volume center. We hypothesized that there would be no between-group differences. Study Design: Cohort study; Level of evidence, 3. Methods: This was a registry study with review of medical records. Our study cohort consisted of patients who underwent primary ACLR with either QT or HT graft performed at Copenhagen University Hospital Hvidovre between January 2015 and December 2018. The cohort was identified from the Danish Knee Ligament Reconstruction Registry and linked to the Danish National Patient Registry to identify all hospital contacts after ACLR. The outcome variables were graft failure (rerupture or >3-mm side-to-side difference in anteroposterior [AP] laxity), revision ACLR, reoperation due to cyclops lesion, reoperation due to meniscal injury, and reoperation due to any reason. AP laxity and pivot shift were assessed at 1 year. Kaplan-Meier estimates were used to evaluate the rates of events at 2 years, and comparison was performed with Cox regression analysis. Results: A total of 475 patients (252 HT, 223 QT) were included. The rate of graft failure at 2 years was 9.4% for the QT group and 11.1% for the HT group ( P = .46). For the QT and HT groups, respectively, the rate of revision ACLR was 2.3% and 1.6% ( P = .60), the rate of reoperation due to cyclops lesion was 5.0% and 2.4% ( P = .13), and the rate of reoperation due to meniscal injury was 4.3% and 7.1% ( P = .16). The rate of reoperation due to any reason was 20.5% and 23.6% ( P = .37). At 1-year follow-up, AP laxity was 1.4 mm for QT and 1.5 mm for HT ( P = .51), and the proportion of patients with a positive pivot shift was 29-30% for both groups. Conclusion: QT and HT grafts yielded similar rates of graft failure, revision ACLR, and reoperation at 2 years of follow-up after ACLR. Graft failure was found in 9% to 11% of patients. Patients with QT ACLR showed a non–statistically significant trend of higher risk for reoperation due to cyclops lesion, and those with HT showed a non–statistically significant trend of higher risk for reoperation due to meniscal injury.
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Heida, Annejet, Lisette J. M. E. van der Does, Ahmed A. Y. Ragab, and Natasja M. S. de Groot. "A Rare Case of the Digenic Inheritance of Long QT Syndrome Type 2 and Type 6." Case Reports in Medicine 2019 (June 20, 2019): 1–4. http://dx.doi.org/10.1155/2019/1384139.
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We report a 37-year-old woman with an out-of-hospital cardiac arrest caused by ventricular fibrillation due to digenic inheritance of long QT syndrome type 2 (KCNH2 gene) and type 6 (KCNE2 gene). During hospitalization, prolonged QTc intervals and frequent episodes of ventricular tachyarrhythmias manifested. Genetic testing identified a mutation of the KCNH2 gene and an unclassified variant, most likely pathogenic, of the KCNE2 gene. This digenic inheritance is extremely rare.
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Hunnicutt, Jennifer L., Chris M. Gregory, Michelle M. McLeod, Shane K. Woolf, Russell W. Chapin, and Harris S. Slone. "Quadriceps Recovery After Anterior Cruciate Ligament Reconstruction With Quadriceps Tendon Versus Patellar Tendon Autografts." Orthopaedic Journal of Sports Medicine 7, no. 4 (April 1, 2019): 232596711983978. http://dx.doi.org/10.1177/2325967119839786.
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Background: Quadriceps tendon (QT) autografts are being increasingly used for anterior cruciate ligament reconstruction (ACLR). A paucity of studies exist that compare QT autografts with alternative graft options. Additionally, concerns exist regarding quadriceps recovery after graft harvest insult to the quadriceps muscle-tendon unit. Purpose/Hypothesis: The purpose of this study was to compare quadriceps recovery and functional outcomes in patients with QT versus bone–patellar tendon–bone (BPTB) autografts. The hypothesis was that those with QT autografts would demonstrate superior outcomes. Study Design: Cohort study; Level of evidence, 3. Methods: Active patients with a history of primary, unilateral ACLR with soft tissue QT or BPTB autografts participated. Quadriceps recovery was quantified using variables of strength, muscle size, and activation. Knee extensor isometric and isokinetic strength was measured bilaterally with an isokinetic dynamometer and normalized to body weight. Quadriceps activation was measured with the superimposed burst technique. The maximal cross-sectional area of each quadriceps muscle was measured bilaterally using magnetic resonance imaging. Assessors of muscle size were blinded to the graft type and side of ACLR. Functional tests included hop tests and step length symmetry during walking, measured via spatiotemporal gait analysis. Self-reported function was determined with the International Knee Documentation Committee (IKDC) questionnaire. Neuromuscular and functional outcomes were expressed as limb symmetry indices (LSIs: [surgical limb/nonsurgical limb]*100%). Wilcoxon rank-sum tests were used to compare the LSIs and IKDC scores between groups. Results: There were 30 study participants (19 male, 11 female; median age, 22 years [range, 14-41 years]; median time since surgery, 8 months [range, 6-23 months]), with 15 patients in each group. There were no significant between-group differences in demographic variables or outcomes. LSIs were not significantly different between the QT versus BPTB group, respectively: knee extensor isokinetic strength at 60 deg/s (median, 70 [range, 41-120] vs 68 [range, 37-83]; P = .285), activation (median, 95 [range, 85-111] vs 92 [range, 82-105]; P = .148), cross-sectional area of the vastus medialis (median, 79 [range, 62-104] vs 77 [range, 62-95]; P = .425), single-leg hop test (median, 88 [range, 35-114] vs 77 [range, 49-100]; P = .156), and step length symmetry (median, 99 [range, 93-104] vs 98 [range, 92-103]; P = .653). The median IKDC scores between the QT and BPTB groups were also not significantly different: 82 (range, 67-94) versus 83 (range, 54-94); respectively ( P = .683). Conclusion: Patients with QT autografts demonstrated similar short-term quadriceps recovery and postsurgical outcomes compared with patients with BPTB autografts.
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Namgung, June. "Electrocardiographic Findings in Takotsubo Cardiomyopathy: ECG Evolution and Its Difference from the ECG of Acute Coronary Syndrome." Clinical Medicine Insights: Cardiology 8 (January 2014): CMC.S14086. http://dx.doi.org/10.4137/cmc.s14086.
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Background Electrocardiogram (ECG) manifestations of takotsubo cardiomyopathy (TC) produce ST-segment elevation or T-wave inversion, mimicking acute coronary syndrome (ACS). We describe the ECG manifestation of TC, including ECG evolution, and its different points from ACS. Methods We studied 37 consecutive patients (age 67 ± 15 years, range 23-89, M:F = 12:25) from March 2004 to November 2012 with a diagnosis of TC who were proven to have apical ballooning on echocardiography or left ventricular angiography and normal coronary artery. We analyzed their standard 12-lead ECGs, including rate, PR interval, QRS duration, corrected QT (QTc) interval, ECG evolutions, and arrhythmia events. Results Two common ECG findings in TC were ST-segment elevation (n = 13, 35%) and T inversion (n = 24, 65%), mostly in the precordial leads. After ST-segment resolution, in a few days (3.5 days), diffuse and often deep T-wave inversion developed. Eight patients (22%) had transient Q-waves lasting a few days in precordial leads. No reciprocal ST-segment depression was noted. T-wave inversion continued for several months. QT prolongation (>440 milliseconds) was observed in 37 patients (97%). There were no significant life-threatening arrhythmias except atrial fibrillation (n = 6, 16%). Conclusion There are distinct differences between the ECGs of TC and ACS. These differences will help to differentiate TC from ACS.
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Chernoby, Katie, Michael F. Lucey, Carrie L. Hartner, Michelle Dehoorne, and Stephanie B. Edwin. "Impact of a clinical decision support tool targeting QT-prolonging medications." American Journal of Health-System Pharmacy 77, Supplement_4 (August 25, 2020): S111—S117. http://dx.doi.org/10.1093/ajhp/zxaa269.
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Abstract Purpose To evaluate the impact of a newly implemented clinical decision support (CDS) tool targeting QT interval–prolonging medications on order verification and provider interventions. Methods A multicenter, retrospective quasi-experimental study was conducted to evaluate provider response to CDS alerts triggered during ordering of QT-prolonging medications for adult patients. The primary outcome was the proportion of orders triggering QTc alerts that were continued without intervention during a specified preimplementation phase (n = 49) and during a postimplementation phase (n = 100). Patient risk factors for QTc prolongation, provider alert response, and interventions to reduce the risk of QTc-associated adverse events were evaluated. Results The rate of order continuation without intervention was 82% in the preimplementation phase and 37% in the postimplementation phase, representing an 55% reduction in continued verified orders following implementation of the QT-focused CDS tool. Most alerts were initially responded to by the prescriber, with pharmacist intervention needed in only 33% of cases. There were no significant differences in patient QTc-related risk factors between the 2 study groups (P = 0.11); the postimplementation group had a higher proportion of patients using at least 2 QTc-prolonging medications (48%, compared to 26% in the preimplementation group; P = 0.02). Conclusion Implementation of the CDS tool was associated with a reduction in the proportion of orders continued without intervention in patients at high risk for QTc-related adverse events.
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Колоцей, Л. В. "Association of Endothelial NO-Syntase Gene C786T Polymorphism with the Development of Drug-Induced Long QT Interval Syndrome Caused by Class III Antiarrhythmic Drugs." Рецепт, no. 4 (September 13, 2022): 542–55. http://dx.doi.org/10.34883/pi.2022.25.4.020.
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Цель. Установить взаимосвязь полиморфизма С786T гена эндотелиальной синтазы оксида азота (NOS3) с электрокардиографическими показателями реполяризации желудочков, а также риском развития лекарственно-индуцированного синдрома удлиненного интервала QT (СУИ QT) и неустойчивой полиморфной желудочковой тахикардии (ЖТ) на фоне приема антиаритмических препаратов III класса.Материалы и методы. В исследование включено 92 пациента: из них 75 (основная группа) – с ишемической болезнью сердца (ИБС) и/или артериальной гипертензией (АГ) и нарушениями ритма сердца, принимавших антиаритмические препараты III класса (амиодарон либо соталол), и 17 (контрольная группа) – с хроническими формами ИБС и/или АГ без анамнеза нарушений ритма сердца. В зависимости от наличия или отсутствия лекарственно-индуцированного СУИ QT, пациенты, принимавшие антиаритмические препараты, были разделены на 2 группы: «СУИ QT» (n=38) и «Без СУИ QT» (n=37). Из 75 пациентов, принимающих антиаритмические препараты III класса, у 10 отмечались пароксизмы неустойчивой полиморфной ЖТ по данным ХМ-ЭКГ. Всем пациентам проводились инструментальные, лабораторные и молекулярно-генетические методы исследования, в том числе определение полиморфизма С786T гена NOS3 с помощью методики полимеразной цепной реакции. Распределение аллелей и генотипов в исследуемых группах пациентов соответствовало равновесию Харди – Вайнберга (p>0,05).Результаты. У пациентов с лекарственно-индуцированным СУИ QT достоверно чаще встречались гомозиготный генотип ТT полиморфизма С786Т гена NOS3 (50,0%) по сравнению с пациентами без лекарственно-индуцированного СУИ QT (24,3%, p=0,039), а также рецессивная аллель Т данного полиморфизма (67,1% против 47,3%, p=0,022). У пациентов с полиморфной ЖТ на фоне лекарственно-индуцированного СУИ QT также чаще встречалcя генотип ТT полиморфизма С786Т гена NOS3 (70,0%) по сравнению с пациентами без неустойчивой полиморфной ЖТ (32,3%, p=0,033), а также аллель Т данного полиморфизма (80,0% против 53,8%, p=0,03). Пациенты с генотипом TT характеризуются увеличением продолжительности корригированного интервала QT (p=0,025) и JT (p=0,045), а также корригированного индекса кардиоэлектрофизиологического баланса (QTc/QRS) (p=0,034) по сравнению с пациентами с генотипом CC полиморфизма С786Т гена NOS3.Риск развития лекарственно-индуцированного СУИ QT на фоне приема антиаритмических препаратов III класса ассоциирован с наличием генотипа ТТ (ОР=1,45, 95% ДИ 1,12–1,87, p=0,005) и аллели Т (ОР=2,07, 95% ДИ 1,17–3,67, p=0,01) полиморфизма С786Т гена NOS3. Риск развития неустойчивой полиморфной ЖТ на фоне приема антиаритмических препаратов III класса также ассоциирован с наличием генотипа ТТ (ОР=4,13, 95% ДИ 2,11–8,12, p<0,0001) и аллели Т (ОР=1,48, 95% ДИ 1,13–1,94, p=0,004)вышеуказанного полиморфизма.Заключение. Установлено статистически значимое преобладание рецессивной аллели T и гомозиготного генотипа ТТ полиморфного варианта С786Т гена NOS3 у пациентов c СУИ QT по сравнению с пациентами без СУИ QT и контрольной группой (p<0,05). Пациенты с наличием аллели T и генотипа TT полиморфизма С786Т гена NOS3 имеют повышенный риск развития лекарственно-индуцированного СУИ QT, вызываемого приемом антиаритмических препаратов III класса, а также неустойчивой полиморфной ЖТ, что может учитываться при дифференцированной терапии пациентов с нарушениями ритма сердца. Purpose. To establish the relationship of C786T polymorphism of the endothelial nitric oxide synthase (NOS3) gene with electrocardiographic indicators of ventricular repolarization, as well as the risk of drug-induced long QT syndrome (LQTS) and non- sustained polymorphic ventricular tachycardia (VT) while taking class III antiarrhythmic drugs.Materials and methods. The study included 92 patients: 75 of them (main group) with coronary heart disease and/or hypertension and cardiac arrhythmias, taking class III antiarrhythmic drugs (amiodarone or sotalol) and 17 (control group) – with chronic forms of coronary artery disease and/or hypertension without a history of cardiac arrhythmias. Depending on the presence or absence of drug-induced LQTS, patients taking antiarrhythmic drugs were divided into 2 groups: "LQTS" (n=38) and "Without LQTS" (n=37). Of the 75 patients taking class III antiarrhythmic drugs, 10 had paroxysms of non- sustained polymorphic VT according to HM-ECG. All patients underwent instrumental, laboratory and molecular genetic research methods, including the determination of the C786T polymorphism of the NOS3 gene using the polymerase chain reaction technique. The distribution of alleles and genotypes in the studied groups of patients corresponded to the Hardy – Weinberg equilibrium (p>0.05).Results. In patients with drug-induced LQTS, the homozygous TT genotype of C786T polymorphism of the NOS3 gene was significantly more common (50.0%) compared with patients without drug-induced LQTS (24.3%, p=0.039), as well as the recessive allele T this polymorphism (67.1% vs 47.3%, p=0.022). In patients with polymorphic VT caused by drug-induced LQTS, the TT genotype of C786T polymorphism of the NOS3 gene was also more common (70.0%) compared with patients without non-sustained polymorphic VT (32.3%, p=0.033), as well as the T allele this polymorphism (80.0% vs 53.8%, p=0.03). Patients with the TT genotype are characterized by an increase in the duration of the corrected QT interval (p=0.025) and JT (p=0.045), corrected CEB index (p=0.034) compared with patients with the CC genotype of the C786T polymorphism of the NOS3 gene. The risk of drug-induced LQTS while taking class III antiarrhythmic drugs is associated with the presence of the TT genotype (RR=1.45, 95% CI 1.12–1.87, p=0.005) and the T allele (RR=2.07, 95% CI 1.17–3.67, p=0.01) of the C786T polymorphism of the NOS3 gene. The risk of non-sustained polymorphic VT while taking class III antiarrhythmic drugs is also associated with the presence of the TT genotype (RR=4.13, 95% CI 2.11–8.12, p<0.0001) and the T allele (RR=1.48, 95% CI 1.13–1.94, p=0.004) of the above mentioned polymorphism.Conclusion. A statistically significant predominance of the recessive T allele and the homozygous TT genotype of the C786T polymorphic variant of the NOS3 gene was found in patients with LQTS compared with patients without LQTS and the control group (p<0.05). Patients with the T allele and the TT genotype of the C786T polymorphism of the NOS3 gene have an increased risk of drug-induced LQTS caused by class III antiarrhythmic drugs, as well as non-sustained polymorphic VT, which can be taken into account in the differentiated therapy of patients with cardiac arrhythmias.
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Jumahat, Shaliza, Gan Kok Beng, Norbahiah Misran, Mohammad Tariqul Islam, Nurhafizah Mahri, and Mohd Hasni Ja’afar. "Automated QT Interval Measurement Using Modified Pan-Tompkins Algorithm with Independent Isoelectric Line Approach." Journal of Biomimetics, Biomaterials and Biomedical Engineering 44 (February 2020): 51–61. http://dx.doi.org/10.4028/www.scientific.net/jbbbe.44.51.
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The QT interval on the electrocardiogram (ECG) signal is known to have an important role in monitoring heart’s electrical activity because the presence of QT interval prolongation can be associated with life-threatening cardiac events. This interval can be identified and measured using either manual or automated techniques. Currently, studies on automated QT interval measurement algorithms are becoming a growing field, as they can provide the best solution to overcome misdiagnosis and timely issues resulting from manual identification. However, the physiological variability of the QRS complex and the fluctuation of the isoelectric line are prevalent issues that need to be considered in the automatic method. In this report, an algorithm to identify the QRS onset and T-wave offset for measuring the corrected QT interval (QTc) is proposed. This method uses an improved Pan-Tompkins algorithm from the previous work with independent of the isoelectric line approach for detecting the QRS onset and the T offset. The algorithm was implemented in Matlab and applied to the 60 seconds duration of 27 records in the PPUKM database with a sampling frequency of 500 Hz. The performance of the algorithm achieved a sensitivity of 100% for QRS onset detection and 100% for T offset detection. As for the accuracy, the algorithm’s performance obtained 100% for QRS onset detection and 99.56% for T offset detection. The mean error results with respect to manual annotation were 37±18.5 ms for QRS onset detection and 32±22.3 ms for T offset detection which was within ANSI/AAMI-EC57:1998 standard tolerance. The proposed algorithm exhibits reliable automated QTc measurement. Besides insensitive to morphological variations of ECG waves, the computational method is simple and possibly implemented as the basis for future software development for portable device applications.
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Pizzuto, Matthew F., Gen Suzuki, Michael D. Banas, Brendan Heavey, James A. Fallavollita, and John M. Canty. "Dissociation of hemodynamic and electrocardiographic indexes of myocardial ischemia in pigs with hibernating myocardium and sudden cardiac death." American Journal of Physiology-Heart and Circulatory Physiology 304, no. 12 (June 15, 2013): H1697—H1707. http://dx.doi.org/10.1152/ajpheart.00166.2013.
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Many survivors of sudden cardiac death (SCD) have normal global ventricular function and severe coronary artery disease but no evidence of symptomatic ischemia or infarction before the development of lethal ventricular arrhythmias, and the trigger for ventricular tachycardia (VT)/ventricular fibrillation (VF) remains unclear. We sought to identify the role of spontaneous ischemia and temporal hemodynamic factors preceding SCD using continuous telemetry of left ventricular (LV) pressure and the ECG for periods up to 5 mo in swine ( n = 37) with hibernating myocardium who experience spontaneous VT/VF in the absence of heart failure or infarction. Hemodynamics and ST deviation at the time of VT/VF were compared with survivors with hibernating myocardium as well as sham controls. All episodes of VT/VF occurred during sympathetic activation and were initiated by single premature ventricular contractions, and the VT degenerated into VF in ∼ 30 s. ECG evidence of ischemia was infrequent and no different from those that survived. Baseline hemodynamics were no different among groups, but LV end-diastolic pressure during sympathetic activation was higher at the time of SCD (37 ± 4 vs. 26 ± 4 mmHg, P < 0.05) and the ECG demonstrated QT shortening (155 ± 4 vs. 173 ± 5 ms, P < 0.05). The week before SCD, both parameters were no different from survivors. These data indicate that there are no differences in the degree of sympathetic activation or hemodynamic stress when VT/VF develops in swine with hibernating myocardium. The transiently elevated LV end-diastolic pressure and QT shortening preceding VT/VF raises the possibility that electrocardiographically silent subendocardial ischemia and/or mechanoelectrical feedback serve as a trigger for the development of SCD in chronic ischemic heart disease.
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McPate, Mark J., Rona S. Duncan, James T. Milnes, Harry J. Witchel, and Jules C. Hancox. "The N588K-HERG K+ channel mutation in the ‘short QT syndrome’: Mechanism of gain-in-function determined at 37°C." Biochemical and Biophysical Research Communications 334, no. 2 (August 2005): 441–49. http://dx.doi.org/10.1016/j.bbrc.2005.06.112.
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Ouwehand, Willem Hendrik, and Nicole Soranzo. "Functional Genomics Approaches to Platelet Signaling." Blood 116, no. 21 (November 19, 2010): SCI—37—SCI—37. http://dx.doi.org/10.1182/blood.v116.21.sci-37.sci-37.
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Abstract Abstract SCI-37 The count, volume and function of platelets varies in the population and there is ample evidence that all 3 quantitative traits (QT) are highly heritable. The control of platelet function is complex with a large number of forward and reverse regulatory pathways that promote and inhibit thrombus formation, respectively. We used 4 parallel genomics approaches with the aim to identify novel regulators of platelet function. First we established a genome-wide expression (GWE) HaemAtlas of all 8 haematological elements, including erythroblasts and megakaryocytes (MKs)(1). Mining of this data identified 279 transcripts that were relatively over-expressed in MKs if compared with the results obtained with the 7 remaining blood cell types. Of these, 75 transcripts encode membrane proteins, many with known and several with a hitherto unknown function (2). Second we determined the platelet response to ADP and a collagen mimetic in 500 healthy subjects of the Platelet Function Cohort (PFC)(3). WGE studies of platelet RNA samples from 37 PFC subjects, selected to be representative of the observed variation, identified 63 transcripts that were correlated with function. Third the 500 PFC samples were typed for 1536 SNPs tagging 108 candidate genes for sequence variation and this identified 19 associations (p-value ≤ 0.005) (3). All 19 QT loci (QTLs), but the GP6 gene, were novel. Based on the above 9 genes were selected for functional studies with platelets from genotyped healthy subjects and by morpholino-based gene knockdown in a model of laser-induced thrombus formation in Danio rerio (2,3). This identified BAMBI, COMMD7, LRRC32 and LRRFIP1 playing a role in the promotion and DCBLD2, ESAM, G6B and GTF2A2 in the inhibition of thrombus formation. Finally 2 of the 15 QTLs for platelet volume and count identified in about 15,000 healthy subjects with genome-wide typing information showed an effect on platelet function demonstrating that sequence variants that modify platelet volume may also exert an effect on function (4). (1) Macaulay, I. C. et al., Comparative gene expression profiling of in vitro differentiated megakaryocytes and erythroblasts identifies novel activatory and inhibitory platelet membrane proteins. Blood 109 (8), 3260 (2007); Watkins, N. A. et al., A HaemAtlas: characterizing gene expression in differentiated human blood cells. Blood 113 (19), e1 (2009); (2) O'Connor, M. N. et al., Functional genomics in zebrafish permits rapid characterization of novel platelet membrane proteins. Blood 113 (19), 4754 (2009).; (3) Jones, C. I. et al., A functional genomics approach reveals novel quantitative trait loci associated with platelet signaling pathways. Blood 114 (7), 1405 (2009); (4) Soranzo, N. et al., A genome-wide meta-analysis identifies 22 loci associated with eight hematological parameters in the HaemGen consortium. Nat Genet 41 (11), 1182 (2009). Disclosures: No relevant conflicts of interest to declare.
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Mistry, Sejal, Ramkiran Gouripeddi, Candace M. Reno, Samir Abdelrahman, Simon J. Fisher, and Julio C. Facelli. "Detecting hypoglycemia-induced electrocardiogram changes in a rodent model of type 1 diabetes using shape-based clustering." PLOS ONE 18, no. 5 (May 18, 2023): e0284622. http://dx.doi.org/10.1371/journal.pone.0284622.
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Sudden death related to hypoglycemia is thought to be due to cardiac arrhythmias. A clearer understanding of the cardiac changes associated with hypoglycemia is needed to reduce mortality. The objective of this work was to identify distinct patterns of electrocardiogram heartbeat changes that correlated with glycemic level, diabetes status, and mortality using a rodent model. Electrocardiogram and glucose measurements were collected from 54 diabetic and 37 non-diabetic rats undergoing insulin-induced hypoglycemic clamps. Shape-based unsupervised clustering was performed to identify distinct clusters of electrocardiogram heartbeats, and clustering performance was assessed using internal evaluation metrics. Clusters were evaluated by experimental conditions of diabetes status, glycemic level, and death status. Overall, shape-based unsupervised clustering identified 10 clusters of ECG heartbeats across multiple internal evaluation metrics. Several clusters demonstrating normal ECG morphology were specific to hypoglycemia conditions (Clusters 3, 5, and 8), non-diabetic rats (Cluster 4), or were generalized among all experimental conditions (Cluster 1). In contrast, clusters demonstrating QT prolongation alone or a combination of QT, PR, and QRS prolongation were specific to severe hypoglycemia experimental conditions and were stratified heartbeats by non-diabetic (Clusters 2 and 6) or diabetic status (Clusters 9 and 10). One cluster demonstrated an arrthymogenic waveform with premature ventricular contractions and was specific to heartbeats from severe hypoglycemia conditions (Cluster 7). Overall, this study provides the first data-driven characterization of ECG heartbeats in a rodent model of diabetes during hypoglycemia.
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Isbister, Geoffrey K., and Corrine R. Balit. "Bupropion Overdose: QTc Prolongation and its Clinical Significance." Annals of Pharmacotherapy 37, no. 7-8 (July 2003): 999–1002. http://dx.doi.org/10.1345/aph.1c481.
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OBJECTIVE: To investigate the cardiotoxicity of bupropion hydrochloride in deliberate self-poisoning. METHODS: A prospective study was conducted in a national poisons information center (PIC) of cases of adult deliberate self-poisoning with medical record follow-up of the patients. Fifty-nine cases of bupropion deliberate self-poisoning managed in the hospital, in which the New South Wales PIC was contacted for advice, were evaluated from November 2000 through July 2001. Clinical effects and electrocardiographic (ECG) parameters (QRS, QT, QTc) were the main outcome measures. RESULTS: ECGs were available for 17 of the 59 patients for analysis, 9 patients (53%) were women, and median patient age was 28 years (interquartile range 22–37). The mean ± SD ingested bupropion dose was 3.8 ± 3.1 g. Tachycardia occurred in 13 patients (76%; 95% CI 50 to 93) and hypertension in 8 patients (47%). There were no reports of hypotension or arrhythmias. There was a significantly increased QTc of 461 ± 34 msec in the patients with bupropion overdose compared with previously developed controls; 13 of the 17 cases had a QTc >440 msec (76%; 95% CI 50 to 93). The uncorrected QT interval did not differ from that of controls. CONCLUSIONS: A moderately prolonged QTc (>440 msec) is common in bupropion overdose. However, this may not be a result of intrinsic cardiac toxicity, but overcorrection of the QTc due to the tachycardia that occurs. It is important that the QTc is interpreted with caution in overdoses of agents that cause significant tachycardia (>100 beats/min).
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Cheney, F. W., M. J. Bishop, B. L. Eisenstein, and L. D. Artman. "Hypoxic pulmonary vasoconstriction does not affect hydrostatic pulmonary edema formation." Journal of Applied Physiology 62, no. 2 (February 1, 1987): 776–80. http://dx.doi.org/10.1152/jappl.1987.62.2.776.
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We studied the effects of regional hypoxic pulmonary vasoconstriction (HPV) on lobar flow diversion in the presence of hydrostatic pulmonary edema. Ten anesthetized dogs with the left lower lobe (LLL) suspended in a net for continuous weighing were ventilated with a bronchial divider so the LLL could be ventilated with either 100% O2 or a hypoxic gas mixture (90% N2–5% CO2–5% O2). A balloon was inflated in the left atrium until hydrostatic pulmonary edema occurred, as evidenced by a continuous increase in LLL weight. Left lower lobe flow (QLLL) was measured by electromagnetic flow meter and cardiac output (QT) by thermal dilution. At a left atrial pressure of 30 +/- 5 mmHg, ventilation of the LLL with the hypoxic gas mixture caused QLLL/QT to decrease from 17 +/- 4 to 11 +/- 3% (P less than 0.05), pulmonary arterial pressure to increase from 35 +/- 5 to 37 +/- 6 mmHg (P less than 0.05), and no significant change in rate of LLL weight gain. Gravimetric confirmation of our results was provided by experiments in four animals where the LLL was ventilated with an hypoxic gas mixture for 2 h while the right lung was ventilated with 100% O2. In these animals there was no difference in bloodless lung water between the LLL and right lower lobe. We conclude that in the presence of left atrial pressures high enough to cause hydrostatic pulmonary edema, HPV causes significant flow diversion from an hypoxic lobe but the decrease in flow does not affect edema formation.
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Karhan, Asuman N., Hayrettin H. Aykan, Ersin Gümüş, Yasemin Dönmez, Dursun Alehan, Süheyla Özkutlu, Hülya Demir, İnci N. Saltık Temizel, Hasan Özen, and Aysel Yüce. "Assessment of cardiac function and electrocardiographic findings in patients with Wilson’s disease." Cardiology in the Young 29, no. 09 (August 28, 2019): 1183–88. http://dx.doi.org/10.1017/s104795111900180x.
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AbstractBackground:This study evaluated cardiac function using tissue Doppler echocardiography and assessed electrocardiographic findings in children diagnosed with Wilson’s disease.Method:Asymptomatic patients with a diagnosis of Wilson’s disease (n = 43) were compared to healthy controls (n = 37) that were age and gender matched.Results:The standard electrocardiographic and conventional echocardiographic examinations were similar in both groups. The left ventricular ejection fraction, shortening fraction, and diastolic function were not significantly different between the two groups. The Tei index for mitral lateral, mitral septal, tricuspid lateral, tricuspid septal, and inter-ventricular septum on tissue Doppler echocardiography was higher in the patient group, yet it did not reach statistical significance. Mitral lateral and septal systolic annular velocity values were significantly lower in the patient group when compared to the control group (p = 0.02 and 0.04, respectively). Also, mitral lateral and septal isovolumetric contraction time values were higher in the patient group (p = 0.04). Although the left ventricular values were not significantly different, relative left ventricular wall thickness was higher in the patient group when compared to the control group, and concentric remodelling in the left ventricle was found in 7 (16%) of 42 patients. QT interval (p = 0.02) and P-wave dispersion values (p = 0.04) were significantly higher in the patient group compared to the control group, and these tend to predict arrhythmias.Conclusion:Our study based on the tissue Doppler echocardiography assessment indicated a subclinical systolic, rather than diastolic, dysfunction in the myocardium with increased QT interval and P-wave dispersion, despite the young age of the patients and short disease duration.
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Cortes, Jorge E., Hagop Kantarjian, James M. Foran, Darejan Ghirdaladze, Mamia Zodelava, Gautam Borthakur, Guy Gammon, et al. "Phase I Study of Quizartinib Administered Daily to Patients With Relapsed or Refractory Acute Myeloid Leukemia Irrespective of FMS-Like Tyrosine Kinase 3–Internal Tandem Duplication Status." Journal of Clinical Oncology 31, no. 29 (October 10, 2013): 3681–87. http://dx.doi.org/10.1200/jco.2013.48.8783.
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Purpose FMS-like tyrosine kinase 3–internal tandem duplication (FLT3-ITD) mutations in acute myeloid leukemia (AML) are associated with early relapse and poor survival. Quizartinib potently and selectively inhibits FLT3 kinase activity in preclinical AML models. Patients and Methods Quizartinib was administered orally at escalating doses of 12 to 450 mg/day to 76 patients (median age, 60 years; range, 23 to 86 years; with a median of three prior therapies [range, 0 to 12 therapies]), enrolled irrespective of FLT3-ITD mutation status in a phase I, first-in-human study in relapsed or refractory AML. Results Responses occurred in 23 (30%) of 76 patients, including 10 (13%) complete remissions (CR) of any type (two CRs, three CRs with incomplete platelet recovery [CRp], five CRs with incomplete hematologic recovery [CRi]) and 13 (17%) with partial remissions (PRs). Of 17 FLT3-ITD–positive patients, nine responded (53%; one CR, one CRp, two CRis, five PRs); of 37 FLT3-ITD–negative patients, five responded (14%; two CRps, three PRs); of 22 with FLT3-ITD–indeterminate/not tested status, nine responded (41%; one CR, three CRis, five PRs). Median duration of response was 13.3 weeks; median survival was 14.0 weeks. The most common drug-related adverse events (> 10% incidence) were nausea (16%), prolonged QT interval (12%), vomiting (11%), and dysgeusia (11%); most were ≤ grade 2. The maximum-tolerated dose was 200 mg/day, and the dose-limiting toxicity was grade 3 QT prolongation. FLT3-ITD phosphorylation was completely inhibited in an in vitro plasma inhibitory assay. Conclusion Quizartinib has clinical activity in patients with relapsed/refractory AML, particularly those with FLT3-ITD, and is associated with an acceptable toxicity profile.
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Mellor, Greg J., Pankaj Panwar, Andrea K. Lee, Christian Steinberg, Julie A. Hathaway, Kirsten Bartels, Susan Christian, et al. "Type 8 long QT syndrome: pathogenic variants in CACNA1C-encoded Cav1.2 cluster in STAC protein binding site." EP Europace 21, no. 11 (August 13, 2019): 1725–32. http://dx.doi.org/10.1093/europace/euz215.
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Abstract Aims Pathogenic gain-of-function variants in CACAN1C cause type-8 long QT syndrome (LQT8). We sought to describe the electrocardiographic features in LQT8 and utilize molecular modelling to gain mechanistic insights into its genetic culprits. Methods and results Rare variants in CACNA1C were identified from genetic testing laboratories. Treating physicians provided clinical information. Variant pathogenicity was independently assessed according to recent guidelines. Pathogenic (P) and likely pathogenic (LP) variants were mapped onto a 3D modelled structure of the Cav1.2 protein. Nine P/LP variants, identified in 23 patients from 19 families with non-syndromic LQTS were identified. Six variants, found in 79% of families, clustered to a 4-residue section in the cytosolic II–III loop region which forms a region capable of binding STAC SH3 domains. Therefore, variants may affect binding of SH3-domain containing proteins. Arrhythmic events occurred in similar proportions of patients with II–III loop variants and with other P/LP variants (53% vs. 48%, P = 0.41) despite shorter QTc intervals (477 ± 31 ms vs. 515 ± 37 ms, P = 0.03). A history of sudden death was reported only in families with II–III loop variants (60% vs. 0%, P = 0.03). The predominant T-wave morphology was a late peaking T wave with a steep descending limb. Exercise testing demonstrated QTc prolongation on standing and at 4 min recovery after exercise. Conclusion The majority of P/LP variants in patients with CACNA1C-mediated LQT8 cluster in an SH3-binding domain of the cytosolic II–III loop. This represents a ‘mutation hotspot’ in LQT8. A late-peaking T wave with a steep descending limb and QT prolongation on exercise are commonly seen.
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Sergeev, E. A., B. I. Geltser, S. M. Kh Said Shokh, V. N. Kotelnikov, and E. V. Markelova. "Assessment of indicators of pulmonary volemia and systemic inflammatory response in patients with comorbidity of chronic obstructive pulmonary disease and ischemic heart disease after coronary artery bypass grafting." Bulletin Physiology and Pathology of Respiration, no. 80 (July 16, 2021): 8–17. http://dx.doi.org/10.36604/1998-5029-2021-80-8-17.
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Inroduction. Systemic inflammatory response (SIR) is an obligatory manifestation of operational stress affecting the functional status of patients, which is important to consider in persons with comorbid pathology.Aim. Evaluation of the relationship between pulmonary volemia and SIR indicators in patients with comorbidity of chronic obstructive pulmonary disease (COPD) and ischemic heart disease (IHD) after coronary artery bypass grafting (CABG).Materials and methods. The study included 76 IHD patients aged 53 to 77 years who underwent CABG. Among the surveyed, 2 groups were identified: 39 patients with IHD and 37 – with a combination of IHD and COPD. The following indices were measured by transpulmonary thermodilution: pulmonary blood volume (PBV), extravascular lung water index (EVLWI), pulmonary vascular permeability index (PVPI), pulmonary shunt fraction (Qs/Qt). Determined the concentration in the blood of interleukin 6 and 10 (IL-6, IL-10), tumor necrosis factor-alpha (TNF-α); transforming growth factor-beta1 (TGFβ1), NLR - the ratio of neutrophils to lymphocytes; PLR – the ratio of platelets to lymphocytes.Results. The most pronounced disturbances in the water balance of the lungs, manifested by an increase in EVLWI, PVPI and Qs/Qt were recorded in patients with comorbidity of COPD and IHD immediately after withdrawal from cardiopulmonary bypass. The PBV level at all measurement points in patients with COPD was lower, which indicated the prevalence of right ventricular failure. SIR on operational stress in this category of patients was manifested by the discoordination of the cytokine profile: a sharp increase in the concentration of IL-6 and IL-10 against the background of a relatively stable level of TNFα and TGF-β1, as well as an increase in NLR and PLR.Conclusion. The unidirectional response of pulmonary volemia and SIR indicators to operational stress indicates the pathophysiological relationship of the studied phenomena.
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Çetin, Mecnun, İbrahim H. Yavuz, Mehmet Gümüştaş, and Göknur Ö. Yavuz. "P wave dispersion, Tpeak–Tend interval, and Tp-e/QT ratio in children with psoriasis." Cardiology in the Young 30, no. 3 (January 8, 2020): 318–22. http://dx.doi.org/10.1017/s1047951119002968.
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AbstractBackground:Psoriasis is a chronic inflammatory, multi-system disease that often begins in childhood and characterised by inflammatory skin, nails, scalp, and joint manifestations. The inflammation in psoriasis may promote some effect on the cardiac conduction system.Objective:The aim of this study is to investigate myocardial repolarisation anomaly on the conducting system in the paediatric psoriasis using P wave dispersion, Tpeak–Tend interval, and Tp-e/QT ratio.Methods:Forty-two patients diagnosed with psoriasis and 37 age- and sex-matched healthy children were enrolled in the study. Electrocardiographic parameters in psoriasis and control group were recorded from an electrocardiogram for each patient.Results:The results indicated that the parameters including Pdis, QTc dis, Tp-e dis interval, and Tp-e max/QTmax ratios, which are known to be key indicators for the prediction of severe atrial or ventricular arrhythmia and sudden cardiac death and also important parameters used as the indicators for the non-invasive evaluation of the transmural heterogeneity were significantly longer in the study group compared to the control group (p < 0.05).Conclusions:This study includes the evidence linking psoriasis with increased myocardial repolarisation heterogeneity. These findings suggest that this patient population may be at an increased risk for arrhythmias. Our findings may be a basis for further studies.
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Dietrichs, Erik S., Karen McGlynn, Andrew Allan, Adam Connolly, Martin Bishop, Francis Burton, Sarah Kettlewell, Rachel Myles, Torkjel Tveita, and Godfrey L. Smith. "Moderate but not severe hypothermia causes pro-arrhythmic changes in cardiac electrophysiology." Cardiovascular Research 116, no. 13 (February 7, 2020): 2081–90. http://dx.doi.org/10.1093/cvr/cvz309.
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Abstract Aims Treatment of arrhythmias evoked by hypothermia/rewarming remains challenging, and the underlying mechanisms are unclear. This in vitro experimental study assessed cardiac electrophysiology in isolated rabbit hearts at temperatures occurring in therapeutic and accidental hypothermia. Methods and results Detailed ECG, surface electrogram, and panoramic optical mapping were performed in isolated rabbit hearts cooled to moderate (31°C) and severe (17°C) hypothermia. Ventricular activation was unchanged at 31°C while action potential duration (APD) was significantly prolonged (176.9 ± 4.2 ms vs. 241.0 ± 2.9 ms, P < 0.05), as was ventricular repolarization. At 17°C, there were proportionally similar delays in both activation and repolarization. These changes were reflected in the QRS and QT intervals of ECG recordings. Ventricular fibrillation threshold was significantly reduced at 31°C (16.3 ± 3.1 vs. 35 ± 3.5 mA, P < 0.05) but increased at 17°C (64.2 ± 9.9, P < 0.05). At 31°C, transverse conduction was relatively unchanged by cooling compared to longitudinal conduction, but at 17°C both transverse and longitudinal conduction were proportionately reduced to a similar extent. The gap junction uncoupler heptanol had a larger relative effect on transverse than longitudinal conduction and was able to restore the transverse/longitudinal conduction ratio, returning ventricular fibrillation threshold to baseline values (16.3 ± 3.1 vs. 36.3 ± 4.3 mA, P < 0.05) at 31°C. Rewarming to 37°C restored the majority of the electrophysiological parameters. Conclusions Moderate hypothermia does not significantly change ventricular conduction time but prolongs repolarization and is pro-arrhythmic. Further cooling to severe hypothermia causes parallel changes in ventricular activation and repolarization, changes which are anti-arrhythmic. Therefore, relative changes in QRS and QT intervals (QR/QTc) emerge as an ECG-biomarker of pro-arrhythmic activity. Risk for ventricular fibrillation appears to be linked to the relatively low temperature sensitivity of ventricular transmural conduction, a conclusion supported by the anti-arrhythmic effect of heptanol at 31°C.
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Loukrakpam, Bidyarani, Laishram Geetanjali, O. Puinabati Luikham, and Sanjoy K. Shylla. "Electrocardiographic changes in patients with pre-eclampsia." Annals of Medical Physiology 3, no. 1 (March 22, 2019): 10–13. http://dx.doi.org/10.23921/amp.2019v3i1.26774.
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Pre-eclampsia is a hypertensive disorder of pregnancy that is associated with elevated maternal risk for cardiovascular disease. Electrocardiographic (ECG) changes in pre-eclampsia have been documented in some studies. Electrocardiography has recently emerged as a useful tool to evaluate cardiovascular complication during and after pregnancy. The present study was therefore undertaken to find out electrocardiographic changes in pre-eclamptic women, visiting Regional Institute of Medical Sciences, Manipur. The aim of this study was to determine the electrocardiographic changes in both pre-eclampsia and age matched normotensive pregnant women. In this study, 25 pregnant women (gestational age >20 weeks) with pre-eclampsia in the range of 18 to 45 years of age were recruited and compared with the equal number of age matched normotensive pregnant women. ECG parameters of pre-eclamptic women were compared with those of normotensive pregnant women. The data were then analyzed using SPSS software. Pre-eclamptic women showed significantly longer QRS (0.10±0.02 sec vs 0.09±0.05 sec), prolonged QT (0.401±0.03 sec vs 0.365±0.003sec) and QTc (457.73±37 msec vs 416.47± 25.4 msec) than control group. The study shows that electrocardiography can be used to evaluate cardiovascular risk in pre-eclamptic women.
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Hohnloser, Stefan H., Frank Baedeker, and Andreas van de Loo. "911-37 Quinidine or Sotalol-induced Changes in QT-Dispersion During Pharmacological Conversion Therapy of Atrial Fibrillation: Link to Proarrhythmia as Assessed in a Prospective, andomized Trial." Journal of the American College of Cardiology 25, no. 2 (February 1995): 66A. http://dx.doi.org/10.1016/0735-1097(95)91726-e.
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Gligic, Branko, Radoslav Romanovic, Goran Radjen, Dragan Tavciovski, Predrag Djuran, and Slobodan Obradovic. "Relationship between QT dispersion and reperfusion in the acute myocardial infarction." Vojnosanitetski pregled 60, no. 1 (2003): 19–27. http://dx.doi.org/10.2298/vsp0301019g.
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Background. QT dispersion (QTd) represents the parameter of the expanded heterogeneity of myocard of ventricles. The aim of this study was to examine the dynamics of changes of QTd during the first 5 days of the acute myocardial infarction (AMI) in dependence to noninvasively estimated success of thrombolytic therapy. Methods. Thirty six patients with AMI were included in the study. All patients were treated with alteplaze according to rapid protocol. QTd (QTc max-QTc min) was measured immediately after the reception (0 min), after the thrombolytic therapy (90 min) and since the 2nd to the 5th day of the hospitalization. Reperfusion was estimated on the basis of electrocardiographic and biohumoral parameters. Results. In the group of 36 patients, 22 male and 11 female, both parameters of the reperfusion were not compatible in 3 patients. The other 23 patients had the reperfusion, while 10 patients did not have it. At the reception there was no significant difference of QTd between the group with reperfusion (79?34 ms) and the group without reperfusion (65?19 ms). After receiving alteplase, the average QTd in the group with reperfusion was 67?31 ms, which was not shorter in relation to the group without reperfusion (70?23 ms). Since the 2nd day of AMI, significantly smaller QTd in patients with reperfusion was not registered compared with the patients without the reperfusion (54?17 vs.73?20 ms), whereas since the 3rd day the difference became significant (46?16 vs. 87?24 ms). On the 4th day it was 43?12 vs. 78?21 ms, and on the 5th day it was 38?11 vs. 62?23 ms. On the 1st day significant difference of QTd between the groups with and without reperfusion was not registered in the group of patients with anterior AMI (0 min: 97?47 vs. 72?16; 90 min 68?47 vs. 72?20) whereas on the 2nd day it became statistically significant (51?15 vs. 74?20 on the 2nd day, 51?20 vs. 88?24 on the 3rd day, 46?10 vs. 81?19 on the 4th day and 40?8 vs. 69?22 ms on the 5th day. In the group of patients with inferolateral AMI, only on the 3rd day significant difference of QTd between the group with and the group without reperfusion was registered (43?14 vs. 69?29 ms), while in all other measuring it was not registered (0 min: 69?22 vs. 42?9; 90 min: 67?20 vs. 67?41; 55?19 vs. 60?25 on the 2nd day; 41?14 vs. 51?6 on the 4th day and 51?12 vs. 37?8 ms on the 5th day). Conclusion. Qt dispersion was of significantly shorter duration in patients with the successfully performed reperfusion in relation to the patients without the reperfusion. In patients with the anterior AMI, QTd was significantly different in patients with in relation to the patients without the reperfusion in distinction with the patients with inferolateral AMI.
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Roozen, Geert V. T., Ruchika Meel, Joyce Peper, William D. F. Venter, Roos E. Barth, Diederick E. Grobbee, Kerstin Klipstein-Grobusch, and Alinda G. Vos. "Electrocardiographic and echocardiographic abnormalities in urban African people living with HIV in South Africa." PLOS ONE 16, no. 2 (February 2, 2021): e0244742. http://dx.doi.org/10.1371/journal.pone.0244742.
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Background Studies from high income countries report that HIV-positive people have an impaired systolic and diastolic cardiac function compared to HIV-negative people. It is unclear if results can be translated directly to the Sub-Saharan Africa context. This study assesses electro- and echocardiographic characteristics in an urban African population, comparing HIV-positive people (treated and not yet treated) with HIV-negative controls. Methods We conducted a cross-sectional study in Johannesburg, South Africa. We enrolled HIV-positive participants from three randomized controlled trials that had recruited participants from routine HIV testing programs. HIV-negative controls were recruited from the community. Data were collected on demographics, cardiovascular risk factors, medical history and electrocardiographic and echocardiographic characteristics. Results In total, 394 HIV-positive participants and 153 controls were enrolled. The mean age of HIV-positive participants was 40±9 years (controls: 35±10 years), and 34% were male (controls: 50%). Of HIV-positive participants 36% were overweight or obese (controls: 44%), 23% had hypertension (controls: 28%) and 12% were current smoker (controls: 37%). Median time since HIV diagnosis was 6.0 years (IQR 2.3–10.0) and median treatment duration was 4.0 years (IQR 0.0–8.0), 50% had undetectable viral load. The frequency of anatomical cardiac abnormalities was low and did not differ between people with and without HIV. We observed no relation between HIV or anti-retroviral therapy (ART) and systolic or diastolic heart function. There was an association between ART use and corrected QT interval: +11.8 ms compared to HIV-negative controls (p<0.01) and +18.9 ms compared to ART-naïve participants (p = 0.01). We also observed a higher left ventricular mass index in participants on ART (+7.8 g/m2, p<0.01), but this association disappeared after adjusting for CD4 cell count, viral load and HIV-duration. Conclusion The low number of major cardiac abnormalities in this relatively young, well managed urban African HIV-positive population is reassuring. The increase in corrected QT interval and left ventricular mass may contribute to higher cardiac mortality and morbidity in people living with HIV in the long term.
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Patel, Salma, Wojciech Zareba, Raymond Woosley, Karolina Perez, Xiaojuan Xia, Chris Wendel, Imran Patel, Jerod Miller, Stuart Quan, and Sairam Parthasarathy. "0441 Positive airway pressure therapy associated changes in ventricular repolarization in patients with heart failure." SLEEP 46, Supplement_1 (May 1, 2023): A196. http://dx.doi.org/10.1093/sleep/zsad077.0441.
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Abstract Introduction Obstructive sleep apnea (OSA) is associated with prolonged ventricular repolarization at baseline that further increases during sleep when an apnea/hypopnea event occurs. Aggressive treatment of OSA with positive airway pressure therapy (PAP) may further prolong ventricular repolarization during apnea/hypopnea events particularly in patients with heart failure (HF). The goal of this study was to evaluate how ventricular repolarization changes during apnea/hypopnea events in patients with heart failure with reduced (HFrEF) and preserved (HFpEF) ejection fraction and in those patients without HF. Methods Thirty patients with OSA in each of the following groups were randomly selected from a dataset of 2,817 patients: HFrEF, HFpEF and no HF failure. Overnight polysomographies (PSG) for these patients were reviewed and beat-to beat measurements during apnea/hypopnea events were obtained at baseline (without PAP) and on the highest PAP setting attempted. Fridericia’s heart rate corrections were used to calculate QTc. QT variability was measured as the standard deviation of QT intervals (SDQT). Results The electrocardiogram was analyzable for n=11 with HFrEF (age 71± 17 years , 91% male) , n=28 with HFpEF (age 71± 12 years , 43% male) and n=30 without HF (age 57± 12 years , 50% male). In those with HFrEF, the mean (SD) QTc increased from 442(12)ms to 452(13)ms and SDQT increased from 9(2) to 13 (2) from baseline to the highest level of PAP attempted. In those with HFpEF, the mean (SD) QTc decreased from 448 (8) to 436 (8) ms and SDQT increased from 10 (1) to 11 (1) from baseline to the highest level of PAP attempted. In those without HF, the mean (SD) QTc increased from 429(37) to 439(56) and SDQT was stable from 8(6) to 8(8) from baseline (no PAP) to the highest level of PAP attempted. There were significant differences noted between the groups in changes in QTc (p=0.002) and SDQT (p=0.048) on PAP when compared to baseline. Conclusion Patients with HFrEF had increases in both QTc and SDQT with PAP at high pressures placing them at greater risk for ventricular arrhythmias. Support (if any) AASM Foundation (203-JF-18), NIH (HL126140, 2L30HL154400-023), University of Arizona (5299903; 5833261; 4258021)
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Dagradi, Federica, Carla Spazzolini, Silvia Castelletti, Matteo Pedrazzini, Maria-Christina Kotta, Lia Crotti, and Peter J. Schwartz. "Exercise Training-Induced Repolarization Abnormalities Masquerading as Congenital Long QT Syndrome." Circulation 142, no. 25 (December 22, 2020): 2405–15. http://dx.doi.org/10.1161/circulationaha.120.048916.
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Background: The diagnosis of long QT syndrome (LQTS) is rather straightforward. We were surprised by realizing that, despite long-standing experience, we were making occasional diagnostic errors by considering as affected subjects who, over time, resulted as not affected. These individuals were all actively practicing sports—an observation that helped in the design of our study. Methods: We focused on subjects referred to our center by sports medicine doctors on suspicion of LQTS because of marked repolarization abnormalities on the ECG performed during the mandatory medical visit necessary in Italy to obtain the certificate of eligibility to practice sports. They all underwent our standard procedures involving both a resting and 12-lead ambulatory ECG, an exercise stress test, and genetic screening. Results: There were 310 such consecutive subjects, all actively practicing sports with many hours of intensive weekly training. Of them, 111 had a normal ECG, different cardiac diseases, or were lost to follow-up and exited the study. Of the remaining 199, all with either clear QTc prolongation and/or typical repolarization abnormalities, 121 were diagnosed as affected based on combination of ECG abnormalities with positive genotyping (QTc, 482±35 ms). Genetic testing was negative in 78 subjects, but 45 were nonetheless diagnosed as affected by LQTS based on unequivocal ECG abnormalities (QTc, 472±33 ms). The remaining 33, entirely asymptomatic and with a negative family history, showed an unexpected and practically complete normalization of the ECG abnormalities (their QTc shortened from 492±37 to 423±25 ms [ P <0.001]; their Schwartz score went from 3.0 to 0.06) after detraining. They were considered not affected by congenital LQTS and are henceforth referred to as “cases.” Furthermore, among them, those who resumed similarly heavy physical training showed reappearance of the repolarization abnormalities. Conclusion: It is not uncommon to suspect LQTS among individuals actively practicing sports based on marked repolarization abnormalities. Among those who are genotype-negative, >40% normalize their ECG after detraining, but the abnormalities tend to recur with resumption of training. These individuals are not affected by congenital LQTS but could have a form of acquired LQTS. Care should be exercised to avoid diagnostic errors.
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Tran, Phu N., Jiansong Sheng, Aaron L. Randolph, Claudia Alvarez Baron, Nicolas Thiebaud, Ming Ren, Min Wu, et al. "Mechanisms of QT prolongation by buprenorphine cannot be explained by direct hERG channel block." PLOS ONE 15, no. 11 (November 6, 2020): e0241362. http://dx.doi.org/10.1371/journal.pone.0241362.
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Buprenorphine is a μ-opioid receptor (MOR) partial agonist used to manage pain and addiction. QTC prolongation that crosses the 10 msec threshold of regulatory concern was observed at a supratherapeutic dose in two thorough QT studies for the transdermal buprenorphine product BUTRANS®. Because QTC prolongation can be associated with Torsades de Pointes (TdP), a rare but potentially fatal ventricular arrhythmia, these results have led to further investigation of the electrophysiological effects of buprenorphine. Drug-induced QTC prolongation and TdP are most commonly caused by acute inhibition of hERG current (IhERG) that contribute to the repolarizing phase of the ventricular action potentials (APs). Concomitant inhibition of inward late Na+ (INaL) and/or L-type Ca2+ (ICaL) current can offer some protection against proarrhythmia. Therefore, we characterized the effects of buprenorphine and its major metabolite norbuprenorphine on cardiac hERG, Ca2+, and Na+ ion channels, as well as cardiac APs. For comparison, methadone, a MOR agonist associated with QTC prolongation and high TdP risk, and naltrexone and naloxone, two opioid receptor antagonists, were also studied. Whole cell recordings were performed at 37°C on cells stably expressing hERG, CaV1.2, and NaV1.5 proteins. Microelectrode array (MEA) recordings were made on human induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs). The results showed that buprenorphine, norbuprenorphine, naltrexone, and naloxone had no effect on IhERG, ICaL, INaL, and peak Na+ current (INaP) at clinically relevant concentrations. In contrast, methadone inhibited IhERG, ICaL, and INaL. Experiments on iPSC-CMs showed a lack of effect for buprenorphine, norbuprenorphine, naltrexone, and naloxone, and delayed repolarization for methadone at clinically relevant concentrations. The mechanism of QTC prolongation is opioid moiety-specific. This remains undefined for buprenorphine, while for methadone it involves direct hERG channel block. There is no evidence that buprenorphine use is associated with TdP. Whether this lack of TdP risk can be generalized to other drugs with QTC prolongation not mediated by acute hERG channel block warrants further study.
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Chistyakova, M. V., and A. V. Govorin. "FEATURES OF HEART LESIONS IN PATIENTS WITH VIRAL LIVER CIRRHOSIS." Rational Pharmacotherapy in Cardiology 14, no. 3 (July 5, 2018): 387–92. http://dx.doi.org/10.20996/1819-6446-2018-14-3-387-392.
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Aim. To study the structural and functional parameters of the heart, as well as the effect of antiviral therapy on certain cardiohemodynamic parameters in patients with viral liver cirrhosis (VLC).Material and methods. 96 patients with VLC (median age 42.1 [36;44] years, median duration of the disease – 3.5 [2.8;6.7] years) were examined. Patients without ascites (n=59) were included into the 1st group, and patients with ascites (n=37) – into the 2nd group. The control group included 21 healthy volunteers. Standard and tissue echocardiography, Holter monitoring of electrocardiogram were performed in all participants.Results. Ventricular extrasystoles (class I to IVB) were found in 8 (13%) patients of the 1st group and in 12 (33%) patients in the 2nd group. The corrected interval of QT in the patients of the 1st group was 457.9 [442;468] msec, in the second group – 478 [433;502] msec, in control – 427.9 [406;438] msec (p<0.001). Supraventricular arrhythmias were represented by supraventricular extrasystoles in 15 (25%) patients of the 1st group and 18 (50%) – of the 2nd group; paroxysmal atrial fibrillation in 2 (3%) and 7 (19%) patients, respectively. The systolic velocity Sm of the lateral wall (3, 9 segments) in patients with ascites was lower by 23% and 25%, respectively, compared with the patients of the 1st group; Tei index increased in patients with ascites compared with the control group and the 1st group, p<0.001. In patients with VLC without ascites, the parameters characterizing the mass of the myocardium of the left ventricle increased, the left atrium and pulmonary artery widened. These disorders increased in patients with ascites; besides the systolic pressure in the pulmonary artery increased, and segmental and global systolic function of the left ventricle decreased. Antiviral therapy was accompanied by a decrease in the mass of the left ventricular myocardium, the index of left atrial volume and systolic pressure in the pulmonary artery.Сonclusion. The increase in the myocardium mass of left ventricle, left atrium, pulmonary artery diameter, as well as cardiac arrhythmia and prolongation of the corrected QT interval were found in patients with VLC without ascites. These changes were more pronounced in patients with ascites, and additionally they increased pressure in the pulmonary artery and decreased systolic function of the ventricles of the heart. The antiviral therapy had a positive effect on some cardiohemodynamic parameters.
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Zhang, Yanmin, Xiaomin Li, Ying Yang, Jie Wang, Xinru Gao, and Mengyun Fan. "The combined novel KCNQ1 frameshift I145Sfs*92 and nonsense W392X variants caused Jervell and Lange-Nielsen syndrome in a Chinese infant presenting with sustained foetal bradycardia." EP Europace 22, no. 12 (August 23, 2020): 1880–84. http://dx.doi.org/10.1093/europace/euaa154.
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Abstract Aims We report clinical and molecular analysis of an infant presenting with foetal bradycardia and clinical outcome of Jervell and Lange-Nielsen syndrome (JLNS). Methods and results Clinical, electrocardiogram (ECG), and echocardiographic data were collected from members in a three-generation family. Whole exomes were amplified and sequenced for proband. The identified variants were verified in the remaining members. The pathogenicity of candidate variants was predicted using multiple software programmes. A 28-year-old non-consanguineous Chinese woman at 23 weeks’ gestation presenting with sustained foetal bradycardia of 100 b.p.m. Immunological disorders and infection were excluded. The infant was delivered at 37 weeks’ gestation with 2700-g birthweight. QTc was prolonged in both ECG and Holter recording. Hearing tests confirmed bilateral sensorineural hearing loss. Genetic testing demonstrated that the infant carried a novel frameshift c.431delC (p.I145Sfs*92) and a novel nonsense c.1175G>A (p.W392X) compound variants of KCNQ1 inherited from mother and father, respectively, in autosomal recessive inheritance. Only relative II-5 carrying heterozygous KCNQ1-I145Sfs*92 variant had prolonged QTc, while the other carriers did not have prolonged QT, suggesting an autosomal dominant inheritance of LQT1 phenotype with incomplete penetrance in the family. Conclusion We report the novel frameshift KCNQ1-I145Sfs*92 and nonsense KCNQ1-W392X compound variants in autosomal recessive inheritance that caused JLNS presenting as sustained foetal bradycardia for the first time. Meanwhile, KCNQ1-I145Sfs*92 heterozygous variant demonstrated LQT1 phenotype in autosomal dominant inheritance with incomplete penetrance.
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Conte, Giulio, Daniel Scherr, Radoslaw Lenarczyk, Estelle Gandjbachkh, Stéphane Boulé, Michael D. Spartalis, Elijah R. Behr, Arthur Wilde, and Tatjana Potpara. "Diagnosis, family screening, and treatment of inherited arrhythmogenic diseases in Europe: results of the European Heart Rhythm Association Survey." EP Europace 22, no. 12 (October 21, 2020): 1904–10. http://dx.doi.org/10.1093/europace/euaa223.
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Abstract The spectrum of inherited arrhythmogenic diseases (IADs) includes disorders without overt structural abnormalities (i.e. primary inherited arrhythmia syndromes) and structural heart diseases (i.e. arrhythmogenic ventricular cardiomyopathy, hypertrophic cardiomyopathy). The aim of this European Heart Rhythm Association (EHRA) survey was to evaluate current clinical practice and adherence to 2015 European Society of Cardiology Guidelines regarding the management of patients with IADs. A 24-item centre-based online questionnaire was presented to the EHRA Research Network Centres and the European Cardiac Arrhythmia Genetics Focus Group members. There were 46 responses from 20 different countries. The survey revealed that 37% of centres did not have any dedicated unit focusing on patients with IADs. Provocative drug challenges were widely used to rule-out Brugada syndrome (BrS) (91% of centres), while they were used in a minority of centres during the diagnostic assessment of long-QT syndrome (11%), early repolarization syndrome (12%), or catecholaminergic polymorphic ventricular tachycardia (18%). While all centres advised family clinical screening with electrocardiograms for all first-degree family members of patients with IADs, genetic testing was advised in family members of probands with positive genetic testing by 33% of centres. Sudden cardiac death risk stratification was straightforward and in line with current guidelines for hypertrophic cardiomyopathy, while it was controversial for other diseases (i.e. BrS). Finally, indications for ventricular mapping and ablation procedures in BrS were variable and not in agreement with current guidelines in up to 54% of centres.
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Romero, Jose R., Alicia Rivera, Adriana Muñiz, Ronald Nagel, and Mary E. Fabry. "Arginine Diet for Sickle Transgenic Mice Reduces Endothelin-1-Stimulated Gardos Channel Activity." Blood 110, no. 11 (November 16, 2007): 3399. http://dx.doi.org/10.1182/blood.v110.11.3399.3399.
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Abstract Arginine (ARG) supplementation (5% arginine in chow) restores plasma ARG levels in S+S-Antilles mice to that found in C57BL mice and is associated with a reduction in Ca++ activated K+ channel (Gardos channel) activity, MCHC and high density red cells (Romero, Blood 99(4):2002). However the mechanisms for these effects are not entirely clear. Endothelin-1 (ET) is a potent vasoconstrictor that has been shown to activate Gardos channel activity and reduce MCHC. We hypothesized that reduced ET could account for the decrease in Gardos channel activity. We report here that arginine diet reduced ET levels in mouse plasma from 137 ± 10 to 89 ± 17 pmol/ml using a modified HPLC technique originally proposed by Kumarathasan (Anal Biochem299:37, 2001). We measured Gardos channel activity in ex vivo red cells as the influx of 86Rb in the presence or absence 10μM clotrimazole. Consistent with our previous report, we observed that ARG supplementation was associated with a decrease in Gardos Channel activity. In addition, incubation of red cells with 500 nmol/L of ET for 15 min at 37°C stimulated an increase in Gardos channel activity in cells from both ARG supplemented vs non-supplemented mice that was sensitive to 1 mmol/L of the specific ET receptor B antagonist, BQ788 (9.4 ± 2.5 vs 14.6 ± 3.8 mmol/L cell x h, respectively). However, the maximal response of the Gardos channel activity to ET was significantly blunted in ARG supplemented vs non-supplemented mice (15.7 ± 2.8 vs 22.1 ± 2.2 mmol/L cell x h, p<0.03, n=5). We also performed QT-RT PCR using Taqman assays on aortas from these mice and observed that mRNA expression of both ET and ET receptor A levels were significantly decreased in ARG supplemented vs non-supplemented mice (p<0.05, n=5) while ET receptor B levels were not significantly affected (n=5). Thus, our results suggest that reduced ET is in part responsible for the blunted Gardos channel activity in arginine supplemented mice and raises the possibility that ET metabolism is modulated by arginine supplementation. We conclude that arginine supplementation of sickle cell patients may have multiple benefits including reduced polymer formation, reduced vasoconstriction, and reduced inflammatory response.
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Real-Delor, Raúl E., Giovanni J. Pirelli-Cubas, Jorge L. Ortiz-Martínez, Andrés E. Orrego-Martínez, Keila N. Mendoza-Ayala, Pamela N. Medina-Valdez, Aurelio L. Larrea-Alarcón, et al. "Frecuencia de prolongación del intervalo QTc en adultos infectados con VIH de Paraguay en 2020." Revista Peruana de Investigación en Salud 5, no. 3 (July 20, 2021): 173–79. http://dx.doi.org/10.35839/repis.5.3.935.
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Introducción: el intervalo QTc prolongado predispone a arritmias graves. Diversos medicamentos, entre ellos los antirretrovirales, pueden prolongarlo. Los objetivos fueron determinar las características demográficas, clínicas y la frecuencia del intervalo QTc prolongado en pacientes con VIH. Métodos: estudio observacional, prospectivo, con grupo control. Se incluyeron varones y mujeres, mayores de 18 años, portadores de infección por VIH, que acudieron al Hospital Nacional (Itauguá, Paraguay) durante 2020. Actuaron como grupo control los estudiantes de Medicina. Se excluyeron todos los sujetos que no dieron su consentimiento y los portadores de arritmias. Se midieron variables demográficas, clínicas, laboratoriales y electrocardiograma de 12 canales en reposo. El estudio contó con la aprobación del Comité de Ética de la Universidad Privada del Este (Paraguay). Resultados: ingresaron al estudio 39 pacientes con VIH y 39 controles sanos. La edad media de los casos fue 37 ± 11 años, siendo 59% del sexo masculino. La comorbilidad más frecuente en los casos fue la obesidad (7,6%). Los valores medios de urea, creatinina, K, Ca y Mg en los casos se hallaban en rango normal. Se detectó 18% de QTc prolongado en casos y 0% en los controles. Estos sujetos con alteración electrocardiográfica se hallaban todos en tratamiento antirretroviral y antibiótico múltiple de conocida asociación con QTc prolongado. Conclusión: la frecuencia de QTc prolongado en pacientes con VIH fue del 18% y en controles sanos fue del 0%. Se recomienda el control periódico del electrocardiograma en pacientes con VIH en tratamiento con fármacos que prolongan el intervalo QT.
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Di Veroli, Giovanni Y., Mark R. Davies, Henggui Zhang, Najah Abi-Gerges, and Mark R. Boyett. "High-throughput screening of drug-binding dynamics to HERG improves early drug safety assessment." American Journal of Physiology-Heart and Circulatory Physiology 304, no. 1 (January 1, 2013): H104—H117. http://dx.doi.org/10.1152/ajpheart.00511.2012.
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The use of computational models to predict drug-induced changes in the action potential (AP) is a promising approach to reduce drug safety attrition but requires a better representation of more complex drug-target interactions to improve the quantitative prediction. The blockade of the human ether-a-go-go-related gene (HERG) channel is a major concern for QT prolongation and Torsade de Pointes risk. We aim to develop quantitative in-silico AP predictions based on a new electrophysiological protocol (suitable for high-throughput HERG screening) and mathematical modeling of ionic currents. Electrophysiological recordings using the IonWorks device were made from HERG channels stably expressed in Chinese hamster ovary cells. A new protocol that delineates inhibition over time was applied to assess dofetilide, cisapride, and almokalant effects. Dynamic effects displayed distinct profiles for these drugs compared with concentration-effects curves. Binding kinetics to specific states were identified using a new HERG Markov model. The model was then modified to represent the canine rapid delayed rectifier K+ current at 37°C and carry out AP predictions. Predictions were compared with a simpler model based on conductance reduction and were found to be much closer to experimental data. Improved sensitivity to concentration and pacing frequency variables was obtained when including binding kinetics. Our new electrophysiological protocol is suitable for high-throughput screening and is able to distinguish drug-binding kinetics. The association of this protocol with our modeling approach indicates that quantitative predictions of AP modulation can be obtained, which is a significant improvement compared with traditional conductance reduction methods.