Long QT syndrome — a cause of sudden death.

Sindrom dugog QT intervala (LQTS) je primarni aritmijski poremećaj koji može dovesti do pojave malignih ventrikularnih aritmija tipa torsades de pointe (TdP) i iznenadne srčane smrti. Obilježja u elektrokardiogramu (EKG) uključuju produljenje korigiranog QT intervala i abnormalnosti T-vala. Do danas identificirana genetska osnova za LQTS uključuje trinaest podložnih gena za LQTS: KCNQ1, KCNH2, SCN5A, ANK2, KCNE1, KCNE2, KCNJ2, CACNA1C, CAV3, SCN4B, AKAP9, SNTA1, i KCNJ5. Najčešći genotip su mutacije KCNQ1 te gotovo polovica pacijenata ima tu vrstu mutacije. Navedeni geni kodiraju ionske kanale i regulatorne proteine koji su uključeni u modulaciju struja srčanog akcijskog potencijala. Stečeni oblici LQTS-a mogu također biti uzrokovani genetskim mutacijama, u tim slučajevima nositelji mutacija razvijaju aritmije isključivo u određenim uvjetima (npr. uporaba određenih lijekova). Trenutna terapija uključuje primjenu beta-blokatora, ugradnju implantabilnog kardioverter defibrilatora (ICD) te simpatičku denervaciju srca. LQTS mutacije povezane su s iznenadnom srčanom smrti kod mladih i veoma mladih; a post-mortem genetska testiranja LQTS gena mogu biti korisna kod procjene uzroka iznenadne neobjašnjive smrti (sudden unexplained death). Kaskadni probir koristan je za identificiranje asimptomatskih članova obitelji koji mogu biti pod povećanim rizikom od iznenadne smrti. U ovom preglednom članku prikazali smo gene povezane s LQTS-om zajedno s opisom povezanih patofizioloških mehanizama.Long QT syndrome (LQTS) is a primary arrhythmic disorder that may lead to the precipitation of torsades de pointe (TdP) and sudden death. Electrocardiogram (ECG) features include prolongation of the corrected QT interval and T-wave abnormalities. The genetic basis of LQTS identified to date includes thirteen susceptibility genes for LQTS: KCNQ1, KCNH2, SCN5A, ANK2, KCNE1, KCNE2, KCNJ2, CACNA1C, CAV3, SCN4B, AKAP9, SNTA1, and KCNJ5. Mutations in KCNQ1 are by far the most frequent genotype with nearly half of the patients carrying KCNQ1 mutations. These genes code for ion channels and regulatory proteins that are involved in the modulation of the currents of the cardiac action potential (AP). Acquired forms of LQTS may also have underlying genetic mutations, in these cases mutation carriers develop arrhythmias only under certain conditions (e.g. use of certain medications). Current therapies include use of beta-blockers, implantable cardioverter defibrillators (ICD) and left cardiac sympathetic denervation. LQTS mutations have been associated with sudden death in the young and very young; and postmortem genetic testing in LQTS genes can be useful when assessing the cause of a sudden unexplained death. Cascade screening is also useful to identify asymptomatic family members that may be at risk of sudden death. Here we have reviewed the genes associated with LQTS along with the description of the related pathophysiological mechanisms

Long QT syndrome — a cause of sudden death.

Sindrom dugog QT intervala (LQTS) je primarni aritmijski poremećaj koji može dovesti do pojave malignih ventrikularnih aritmija tipa torsades de pointe (TdP) i iznenadne srčane smrti. Obilježja u elektrokardiogramu (EKG) uključuju produljenje korigiranog QT intervala i abnormalnosti T-vala. Do danas identificirana genetska osnova za LQTS uključuje trinaest podložnih gena za LQTS: KCNQ1, KCNH2, SCN5A, ANK2, KCNE1, KCNE2, KCNJ2, CACNA1C, CAV3, SCN4B, AKAP9, SNTA1, i KCNJ5. Najčešći genotip su mutacije KCNQ1 te gotovo polovica pacijenata ima tu vrstu mutacije. Navedeni geni kodiraju ionske kanale i regulatorne proteine koji su uključeni u modulaciju struja srčanog akcijskog potencijala. Stečeni oblici LQTS-a mogu također biti uzrokovani genetskim mutacijama, u tim slučajevima nositelji mutacija razvijaju aritmije isključivo u određenim uvjetima (npr. uporaba određenih lijekova). Trenutna terapija uključuje primjenu beta-blokatora, ugradnju implantabilnog kardioverter defibrilatora (ICD) te simpatičku denervaciju srca. LQTS mutacije povezane su s iznenadnom srčanom smrti kod mladih i veoma mladih; a post-mortem genetska testiranja LQTS gena mogu biti korisna kod procjene uzroka iznenadne neobjašnjive smrti (sudden unexplained death). Kaskadni probir koristan je za identificiranje asimptomatskih članova obitelji koji mogu biti pod povećanim rizikom od iznenadne smrti. U ovom preglednom članku prikazali smo gene povezane s LQTS-om zajedno s opisom povezanih patofizioloških mehanizama.Long QT syndrome (LQTS) is a primary arrhythmic disorder that may lead to the precipitation of torsades de pointe (TdP) and sudden death. Electrocardiogram (ECG) features include prolongation of the corrected QT interval and T-wave abnormalities. The genetic basis of LQTS identified to date includes thirteen susceptibility genes for LQTS: KCNQ1, KCNH2, SCN5A, ANK2, KCNE1, KCNE2, KCNJ2, CACNA1C, CAV3, SCN4B, AKAP9, SNTA1, and KCNJ5. Mutations in KCNQ1 are by far the most frequent genotype with nearly half of the patients carrying KCNQ1 mutations. These genes code for ion channels and regulatory proteins that are involved in the modulation of the currents of the cardiac action potential (AP). Acquired forms of LQTS may also have underlying genetic mutations, in these cases mutation carriers develop arrhythmias only under certain conditions (e.g. use of certain medications). Current therapies include use of beta-blockers, implantable cardioverter defibrillators (ICD) and left cardiac sympathetic denervation. LQTS mutations have been associated with sudden death in the young and very young; and postmortem genetic testing in LQTS genes can be useful when assessing the cause of a sudden unexplained death. Cascade screening is also useful to identify asymptomatic family members that may be at risk of sudden death. Here we have reviewed the genes associated with LQTS along with the description of the related pathophysiological mechanisms

Time‐dependent antiarrhythmic effects of flecainide on induced atrial fibrillation in horses

Background, Objective: Pharmacological treatment of atrial fibrillation (AF) in horses can be challenging because of low efficacy and adverse effects. Flecainide has been tested with variable efficacy. To test whether the efficacy of flecainide is dependent on AF duration. Animals and Methods: Nine Standardbred mares. Factorial study design. All horses were instrumented with a pacemaker and assigned to a control or an AF group. On day 0, all horses were in sinus rhythm and received 2 mg/kg flecainide IV. Atrial fibrillation subsequently was induced in the AF group by pacemaker stimulation. On days 3, 9, 27, and 55, flecainide was administered to all horses, regardless of heart rhythm. Results: Conclusions and Clinical ImportanceAll horses in AF cardioverted to sinus rhythm on days 3 and 9. On day 27, 5/6 horses cardioverted, whereas only 2/6 cardioverted on day 55. The time from the start of flecainide infusion to cardioversion (range, 3-185min, log transformed) showed linear correlation with the cumulative duration of AF (r(2)=.80, P<.0001). Flecainide induced abnormal QRS complexes in 4/6 AF horses and 1/3 controls. A positive correlation was found between heart rate before flecainide infusion and number of abnormal QRS complexes (0.14, P<.05). One horse suffered from cardiac arrest and died after flecainide infusion. Flecainide is effective for cardioversion of short-term induced AF, but the effect decreases with AF duration. Controlling heart rate may minimize adverse effects caused by flecainide, but the drug should be used with great caution

Mobile app-based symptom-rhythm correlation assessment in patients with persistent atrial fibrillation

Background: The assessment of symptom-rhythm correlation (SRC) in patients with persistent atrial fibrillation (AF) is challenging. Therefore, we performed a novel mobile app-based approach to assess SRC in persistent AF.Methods: Consecutive persistent AF patients planned for electrical cardioversion (ECV) used a mobile app to record a 60-s photoplethysmogram (PPG) and report symptoms once daily and in case of symptoms for four weeks prior and three weeks after ECV. Within each patient, SRC was quantified by the SRC-index defined as the sum of symptomatic AF recordings and asymptomatic non-AF recordings divided by the sum of all recordings.Results: Of 88 patients (33% women, age 68 +/- 9 years) included, 78% reported any symptoms during recordings. The overall SRC-index was 0.61 (0.44-0.79). The study population was divided into SRC-index tertiles: low (= 0.73). Patients within the low (vs high) SRC-index tertile had more often heart failure and diabetes mellitus (both 24.1% vs 6.9%). Extrasystoles occurred in 19% of all symptomatic non-AF PPG recordings. Within each patient, PPG recordings with the highest (vs lowest) tertile of pulse rates conferred an increased risk for symptomatic AF recordings (odds ratio [OR] 1.26, 95% coincidence interval [CI] 1.04-1.52) and symptomatic non-AF recordings (OR 2.93, 95% CI 2.16-3.97). Pulse variability was not associated with reported symptoms.Conclusions: In patients with persistent AF, SRC is relatively low. Pulse rate is the main determinant of reported symptoms. Further studies are required to verify whether integrating mobile app-based SRC assessment in current workflows can improve AF management