Short QT Interval Research Articles

A NOS1AP gene variant is associated with a paradoxical increase of the QT-interval shortening effect of digoxin.

Digoxin is characterized by a small therapeutic window and a QT-interval shortening effect. Moreover, it has been shown that the genetic variants of the nitric oxide synthase-1 adaptor protein (NOS1AP) gene are associated with QT-interval prolongation. We investigated whether the rs10494366 variant of the NOS1AP gene decreases the QT-interval shortening effect of digoxin in patients using this drug. We included 10,057 individuals from the prospective population-based cohort of the Rotterdam Study during a median of 12.2 (interquartile range (IQR) 6.7-18.1) years of follow-up. At study entry, the mean age was 64 years and almost 59% of participants were women. A total of 23,179 ECGs were longitudinally recorded, of which 334 ECGs were from 249 individuals on digoxin therapy. The linear mixed model analysis was used to estimate the effect of the rs10494366 variant on the association between digoxin use and QT-interval duration, adjusted for age, sex, RR interval, diabetes, heart failure, and history of myocardial infarction. In non-users of digoxin, the GG genotype was associated with a significant 6.5 ms [95% confidence interval (CI) 5.5; 7.5] longer QT-interval duration than the TT variant. In current digoxin users, however, the GG variant was associated with a significantly -23.9 [95%CI -29.5; -18.5] ms shorter mean QT-interval duration than in those with the TT variant with -15.9 [95%CI -18.7; -13.1]. This reduction was strongest in the high digoxin dose category [≥0.250 mg/day] with the GG genotype group, with -40.8 [95%CI -52.5; -29.2] ms changes compared to non-users. Our study suggests that the minor homozygous GGgenotype group of the NOS1AP gene rs10494366 variant is associated with a paradoxical increase of the QT-interval shortening effect of digoxin in a population of European ancestry.

Electrocardiographic Scaling Reveals Differences in Electrocardiogram Interval Durations Between Marine and Terrestrial Mammals.

Although the ability of marine mammals to lower heart rates for extended periods when diving is well documented, it is unclear whether marine mammals have electrophysiological adaptations that extend beyond overall bradycardia. We analyzed electrocardiographic data from 50 species of terrestrial mammals and 19 species of marine mammals to determine whether the electrical activity of the heart differs between these two groups of mammals. We also tested whether physiological state (i.e., anesthetized or conscious) affects electrocardiogram (ECG) parameters. Analyses of ECG waveform morphology (heart rate, P-wave duration, and PQ, PR, QRS, and QT intervals) revealed allometric relationships between body mass and all ECG intervals (as well as heart rate) for both groups of mammals and specific differences in ECG parameters between marine mammals and their terrestrial counterparts. Model outputs indicated that marine mammals had 19% longer P-waves, 24% longer QRS intervals, and 21% shorter QT intervals. In other words, marine mammals had slower atrial and ventricular depolarization, and faster ventricular repolarization than terrestrial mammals. Heart rates and PR intervals were not significantly different between marine and terrestrial mammals, and physiological state did not significantly affect any ECG parameter. On average, ECG interval durations of marine and terrestrial mammals scaled with body mass to the power of 0.21 (range: 0.19–0.23) rather than the expected 0.25—while heart rate scaled with body mass to the power of –0.22 and was greater than the widely accepted –0.25 derived from fractal geometry. Our findings show clear differences between the hearts of terrestrial and marine mammals in terms of cardiac timing that extend beyond diving bradycardia. They also highlight the importance of considering special adaptations (such as breath-hold diving) when analyzing allometric relationships.

ATP1A3-Encoded Sodium-Potassium ATPase Subunit Alpha 3 D801N Variant Is Associated With Shortened QT Interval and Predisposition to Ventricular Fibrillation Preceded by Bradycardia.

BackgroundPathogenic variation in the ATP1A3‐encoded sodium‐potassium ATPase, ATP1A3, is responsible for alternating hemiplegia of childhood (AHC). Although these patients experience a high rate of sudden unexpected death in epilepsy, the pathophysiologic basis for this risk remains unknown. The objective was to determine the role of ATP1A3 genetic variants on cardiac outcomes as determined by QT and corrected QT (QTc) measurements.Methods and ResultsWe analyzed 12‐lead ECG recordings from 62 patients (male subjects=31, female subjects=31) referred for AHC evaluation. Patients were grouped according to AHC presentation (typical versus atypical), ATP1A3 variant status (positive versus negative), and ATP1A3 variant (D801N versus other variants). Manual remeasurements of QT intervals and QTc calculations were performed by 2 pediatric electrophysiologists. QTc measurements were significantly shorter in patients with positive ATP1A3 variant status (P<0.001) than in patients with genotype‐negative status, and significantly shorter in patients with the ATP1A3‐D801N variant than patients with other variants (P<0.001). The mean QTc for ATP1A3‐D801N was 344.9 milliseconds, which varied little with age, and remained <370 milliseconds throughout adulthood. ATP1A3 genotype status was significantly associated with shortened QTc by multivariant regression analysis. Two patients with the ATP1A3‐D801N variant experienced ventricular fibrillation, resulting in death in 1 patient. Rare variants in ATP1A3 were identified in a large cohort of genotype‐negative patients referred for arrhythmia and sudden unexplained death.ConclusionsPatients with AHC who carry the ATP1A3‐D801N variant have significantly shorter QTc intervals and an increased likelihood of experiencing bradycardia associated with life‐threatening arrhythmias. ATP1A3 variants may represent an independent cause of sudden unexplained death. Patients with AHC should be evaluated to identify risk of sudden death.

Primary hyperparathyroidism associated with acquired long QT interval and ventricular tachycardia.

SummaryWe present a 54-year-old patient admitted to the emergency department due to loss of consciousness. The initial ECG registered monomorphic ventricular extrasystoles and prolonged QT interval (QT corrected (QTc) >500 ms). Sustained ventricular tachycardia (VT) was registered on 24-h Holter ECG monitoring, which clinically was presented as a crisis of consciousness. Coronary angiography and other visualization methods were normal. Implantable cardioverter-defibrillator (ICD) implantation was planned for the purpose of secondary prevention of sudden cardiac death (SCD). Laboratory and hormonal analyzes revealed primary hyperparathyroidism (PHPT), chronic kidney disease, and hypokalemia. Neck ultrasound showed a 25 mm, sharply outlined homogenous tumor mass which was separated from thyroid gland (TG) and exerted a mild impression on lower parts of the left lobe. Dual wash technetium-99m sestamibi parathyroid scintigraphy with single-photon emission CT (SPECT)/CT also showed the uptake of tracer behind the lower half of the left lobe of the TG. Surgical treatment, lower left parathyroidectomy, was performed, and pathohistological analysis verified parathyroid adenoma. The patient was rhythmically and hemodynamically stable for 7 days after surgery, without additional complaints, and was discharged from the hospital. Timely diagnosis of PHPT, correct assessment and surgical treatment, did not lead our patient to unnecessary ICD implantation. Our case suggests an additional intertwining of electrolyte disorders and ventricular arrhythmias in PHPT and more importantly emphasizes the need for caution when indicating ICD, even in patients with the most serious life-threatening arrhythmias.Learning pointsElectrolyte abnormalities in PHPT can have highly malignant consequences, and the occurrence of hypokalemia in the presence of hypercalcemia is underestimated in PHPT, and the consequences can be life-threatening.Although hypercalcemia causes shortened QT interval, concomitant severe hypokalemia may overcome hypercalcemia and prolong QT interval, even in the absence of structural heart disease or LQTS.Timely diagnosis of PHPT, correct assessment and surgical treatment, do not lead to unnecessary ICD implantation.

Rediscovering Clinical Utility of QT Dispersion: A Long-Forgotten Parameter

Clinical and experimental electrophysiological studies have shown the importance of inhomogeneous myocardial repolarization in ventricular arrhythmias' genesis. Increased dispersion of repolarisation provides a substrate for ventricular arrhythmias by generating functional unidirectional block areas, thereby predisposing to reentry. QT dispersion, defined as the difference between the longest and the shortest QT interval on the surface ECG, is a validated measure of repolarisation dispersion. QT dispersion predicts sudden death and ventricular arrhythmias in patients with chronic heart failure from coronary heart disease and various cardiac diseases

Patients With Primary Hyperparathyroidism Have Shorter QT/QTc Intervals

Background: Previous studies suggest that patients with primary hyperparathyroidism (PHPT) have subclinical cardiovascular disease, but data regarding cardiac conduction abnormalities are limited. The aim of this study was to assess cardiac conduction abnormalities in patients with PHPT compared to controls with thyroid disease (TD). Method: We conducted a retrospective analysis of patients over 40 years of age who underwent parathyroidectomy or thyroidectomy at a single tertiary institution between 2013 and 2018. Demographics and EKG parameters from pre-operative EKG reports were compared using the Mann-Whitney U and Chi Square tests. Regression was used to compare EKG differences between the PHPT and control groups adjusted for sex, age, and other variables found to be significant on univariate analysis. Results: A total of 1181 patients were analyzed, 51% in the PHPT group (n=602) and 49% in the TD group (n=579). The median age was 60.5 years (IQR 53.5–67.9) and there was no difference in sex between the cohorts. PHPT patients had a higher prevalence of hyperlipidemia (HLD, 49% vs 36%, p<0.001) and hypertension (HTN, 50.7% vs 42.1%, p<0.01), but had no differences in EKG rhythm patterns or prevalence of arrhythmia compared to TD patients. As expected, mean serum calcium levels were higher for the PHPT group, 10.74 (0.66) vs 9.53 (0.44). However, the PHPT group included both normocalcemic and hypercalcemic patients. The PHPT group had a lower median QT interval compared to the TD group, 386ms (IQR 368–406) vs 398ms (IQR 376–418), p<0.001 and a higher median PR value, 158ms (IQR 144–174.5) vs 156ms (IQR 143.5–171), p<0.05. More PHPT patients (n=21, 3.5%) had a short QTc interval (<360ms males/<370ms females), compared to TD controls (n=1, 0.2%). Among PHPT patients with a short QT interval, the proportion of patients with hypercalcemia (95%) was higher than that of the PHPT group overall (75%). On multivariable analysis, PHPT patients had a shorter QT interval than TD controls after controlling for sex, age, HLD, HTN. There was no difference between PHPT and TD when serum calcium was included in the model, suggesting that calcium mediates the relationship between QT interval and disease status. Conclusion: PHPT patients have shorter QT/QTc intervals compared to TD controls, but no increased prevalence of arrythmia at baseline. While the QT interval was associated with degree of serum calcium elevation, these findings in a large cohort suggest that PHPT is not associated with arrythmia at baseline among those undergoing parathyroidectomy.

Diagnostic accuracy of the response to the brief tachycardia provoked by standing in children suspected for long QT syndrome.

BackgroundAdult long QT syndrome (LQTS) patients have inadequate corrected QT interval (QTc) shortening and an abnormal T-wave response to the sudden heart rate acceleration provoked by standing. In adults, this knowledge can be used to aid an LQTS diagnosis and, possibly, for risk stratification. However, data on the diagnostic value of the standing test in children are currently limited.ObjectiveTo determine the potential value of the standing test to aid LQTS diagnostics in children.MethodsIn a prospective cohort including children (≤18 years) who had a standing test, comprehensive analyses were performed including manual and automated QT interval assessments and determination of T-wave morphology changes.ResultsWe included 47 LQTS children and 86 control children. At baseline, the QTc that identified LQTS children with a 90% sensitivity was 435 ms, which yielded a 65% specificity. A QTc ≥ 490 ms after standing only slightly increased sensitivity (91%, 95% confidence interval [CI]: 80%–98%) and slightly decreased specificity (58%, 95% CI: 47%–70%). Sensitivity increased slightly more when T-wave abnormalities were present (94%, 95% CI: 82%–99%; specificity 53%, 95% CI: 42%–65%). When a baseline QTc ≥ 440 ms was accompanied by a QTc ≥ 490 ms and T-wave abnormalities after standing, sensitivity further increased (96%, 95% CI: 85%–99%) at the expense of a further specificity decrease (41%, 95% CI: 30%–52%). Beat-to-beat analysis showed that 30 seconds after standing, LQTS children had a greater increase in heart rate compared to controls, which was more evidently present in LQTS boys and LQTS type 1 children.ConclusionIn children, the standing test has limited additive diagnostic value for LQTS over a baseline electrocardiogram, while T-wave abnormalities after standing also have limited additional value. The standing test for LQTS should only be used with caution in children.

High heart rate associated early repolarization causes J-waves in both zebra finch and mouse.

High heart rates are a feature of small endothermic—or warm‐blooded—mammals and birds. In small mammals, the QT interval is short, and local ventricular recordings reveal early repolarization that coincides with the J‐wave on the ECG, a positive deflection following the QRS complex. Early repolarization contributes to short QT‐intervals thereby enabling brief cardiac cycles and high heart rates. We therefore hypothesized high hearts rates associate with early repolarization and J‐waves on the ECG of endothermic birds. We tested this hypothesis by comparing isolated hearts of zebra finches and mice and recorded pseudo‐ECGs and optical action potentials (zebra finch, n = 8; mouse, n = 8). In both species, heart rate exceeded 300 beats per min, and total ventricular activation was fast (QRS < 10 ms). Ventricular activation progressed from the left to the right ventricle in zebra finch, whereas it progressed from apex‐to‐base in mouse. In both species, the early repolarization front followed the activation front, causing a positive J‐wave in the pseudo‐ECG. Inhibition of early repolarization by 4‐aminopyridine reduced J‐wave amplitude in both species. Action potential duration was similar between ventricles in zebra finch, whereas in mouse the left ventricular action potential was longer. Accordingly, late repolarization had opposite directions in zebra finch (left‐right) and mouse (right‐left). This caused a similar direction for the zebra finch J‐wave and T‐wave, whereas in the mouse they were discordant. Our findings demonstrate that early repolarization and the associated J‐wave may have evolved by convergence in association with high heart rates.

Transient receptor potential vanilloid 4 channel participates in mouse ventricular electrical activity.

The TRPV4 channel is a calcium-permeable channel (PCa/PNa ∼ 10). Its expression has been reported in ventricular myocytes, where it is involved in several cardiac pathological mechanisms. In this study, we investigated the implication of TRPV4 in ventricular electrical activity. Left ventricular myocytes were isolated from trpv4+/+ and trpv4-/- mice. TRPV4 membrane expression and its colocalization with L-type calcium channels (Cav1.2) was confirmed using Western blot biotinylation, immunoprecipitation, and immunostaining experiments. Then, electrocardiograms (ECGs) and patch-clamp recordings showed shortened QTc and action potential (AP) duration in trpv4-/- compared with trpv4+/+ mice. Thus, TRPV4 activator GSK1016790A produced a transient and dose-dependent increase in AP duration at 90% of repolarization (APD90) in trpv4+/+ but not in trpv4-/- myocytes or when combined with TRPV4 inhibitor GSK2193874 (100 nM). Hence, GSK1016790A increased calcium transient (CaT) amplitude in trpv4+/+ but not in trpv4-/- myocytes, suggesting that TRPV4 carries an inward Ca2+ current in myocytes. Conversely, TRPV4 inhibitor GSK2193874 (100 nM) alone reduced APD90 in trpv4+/+ but not in trpv4-/- myocytes, suggesting that TRPV4 prolongs AP duration in basal condition. Finally, introducing TRPV4 parameters in a mathematical model predicted the development of an inward TRPV4 current during repolarization that increases AP duration and CaT amplitude, in accord with what was found experimentally. This study shows for the first time that TRPV4 modulates AP and QTc durations. It would be interesting to evaluate whether TRPV4 could be involved in long QT-mediated ventricular arrhythmias.NEW & NOTEWORTHY Transient receptor potential vanilloid 4 (TRPV4) is expressed at the membrane of mouse ventricular myocytes and colocalizes with non-T-tubular L-type calcium channels. Deletion of trpv4 gene in mice results in shortened QT interval on electrocardiogram and reduced action potential duration of ventricular myocytes. Pharmacological activation of TRPV4 channel leads to increased action potential duration and increased calcium transient amplitude in trpv4-/- but not in trpv4-/- ventricular myocytes. To the contrary, TRPV4 channel pharmacological inhibition reduces action potential duration in trpv4+/+ but not in trpv4-/- myocytes. Integration of TRPV4 channel in a computational model of mouse action potential shows that the channel carries an inward current contributing to slowing down action potential repolarization and to increase calcium transient amplitude, similarly to what is observed experimentally. This study highlights for the first time the involvement of TRPV4 channel in ventricular electrical activity.

Long-term prognosis of short QT interval in Korean patients: a multicenter retrospective cohort study

BackgroundShort QT syndrome is a rare, inherited channelopathy associated with sudden cardiac arrest (SCA) but the characteristics and prognosis of short QT interval (SQTI) in Korean patients remain unclear. This study aimed to determine the clinical characteristics and outcomes of SQTI in a Korean population.MethodsConsecutive patients with SQTI from January 1999 to March 2019 in three university hospitals in South Korea were recruited. SQTI was defined as a Bazett’s formula-corrected QT interval (QTc) ≤ 340 ms in serial electrocardiograms. Age- and sex-matched patients with a normal QTc and without overt cardiovascular disease were included in a 1:4 ratio. Clinical and ECG features and outcomes were compared between patients with and without SQTI.Results34 patients with SQTI [age, 23.5 (21–30.5) years; 31 male] were followed up for 4.8 (2.0–7.8) years. Early repolarization, tall T wave, and U wave were significantly more frequent in patients with SQTI than in those without SQTI. QT dispersion [44.0 (28.0–73.0) vs. 20.0 (12.0–35.0) ms, P < 0.001] was significantly wider and heart rate [52.0 (47.0–58.0) vs. 70.0 (62.3–84.0)/min, P < 0.001] was significantly slower in patients with SQTI than in those without. Atrial fibrillation (AF, 11.8% vs. 2.2%, P = 0.030) and ventricular arrhythmia (VA)/SCA (8.7% vs. 0%, P = 0.007) were significantly more frequent in patients with SQTI than in those without. SQTI was significantly associated with AF [odds ratio, 5.911; 95% confidence interval, 1.257–27.808; P = 0.025] and VA/SCA.ConclusionsIn this subset of Korean population, SQTI was associated with AF and VA/SCA.

In Silico Investigation of CACNA2D1 S755T Mutation Associated With Short QT Syndrome

Short QT syndrome (SQTS) is a genetic disease characterized by constantly short QT intervals and high risks of sudden death. SQTS6 is one of the identified SQTS genotype variants associated with the CACNA2D1 S755T mutation. However, the pathogenesis of SQTS induced arrhythmias remains unclear. To identify the underlying mechanisms of SQTS6 induced arrhythmias, a multi-scale human ventricle model comprising cell to organ levels was built. Cellular data was fitted at the cell level to reproduce the electrophysiological alterations reported in experiments. The influences were further explored at tissue and organ levels using idealized strand or tissue sheet models, and realistic ventricular slice and three-dimensional organ models. Simulation results suggested that, at the cellular level, the action potential duration (APD) and the effective refractory period (ERP) of myocytes were significantly abbreviated in the mutation condition. The unevenly changed APD and ERP led to transmural heterogeneity remodeling, and resulted in decreased temporal vulnerability. In addition, the S755T mutation shortened the critical length for initiating reentrant spiral waves, which enhanced the spatial vulnerability and provided substrates for reentry arrhythmias. Regarding the sustainability of arrhythmias, the evoked spiral waves or scroll waves persisted in the mutation condition but did not persist in the wild-type condition. The present study clearly suggested that the CACNA1DC S755T mutation can facilitate the initiation and maintenance of ventricular arrhythmias, and therefore contributes to higher risks of ventricular arrhythmias in SQTS6 patients.

Testosterone use and shorter electrocardiographic QT interval duration in men living with and without HIV.

Testosterone usage (T-use) may alter risk factors for sudden cardiac death in men living with HIV (MLWH). Electrocardiographic QT interval prolongation, which could potentiate ventricular arrhythmias, has previously been associated with HIV infection and, separately, with low testosterone levels. We investigated whether T-use shortens the QT interval duration in MLWH and HIV-uninfected men. We utilized data from the Multicenter AIDS Cohort Study, a prospective, longitudinal study of HIV infection among men who have sex with men. Multivariable linear regression analyses were used to evaluate associations between T-use and corrected QT interval (QTc) duration. Testosterone usage was more common in MLWH compared with HIV-uninfected men (19% vs. 9%). In a multivariable regression analysis, T-use was associated with a 5.7ms shorter QT interval [95% confidence interval (CI): -9.5 to -1.9; P=0.003). Furthermore, stronger associations were observed for prolonged duration of T-use and recent timing of T-use. This study is the first known analysis of T-use and QTc interval in MLWH. Overall, our data demonstrate that recent T-use is associated with a shorter QTc interval. Increased T-use duration above a threshold of ≥50% of visits in the preceding 5years was associated with a shorter QTc interval while lesser T-use duration was not.

The impact of fever on myocardial repolarization parameters

Background:It has been reported in the literature that the increase in body temperature shortens QT interval on electrocardiogram through heart rate modulation. However, the effects of fever on ventricular repolarization are not clearly known. This study elaborates on QT interval of isolated fever, corrected QT (cQT), Tp-e interval, the ratio of corrected Tp-e (cTp-e) and Tp-e/QT, and their impacts on arrhythmia potential.Methods:This prospective study was performed on 74 patients without any active and chronic diseases other than fever and upper respiratory tract infection. The study included patients at the age of 18–50 years suffering from fever above 38.2 °C. QT and Tp-e intervals of the patients were measured from their ECGs taken in febrile and afebrile periods. cQT and cTp-e values were calculated according to Bazett, Fridericia, and Framingham formulations.Results:QT and Tp-e intervals were observed to be shorter in the febrile period (p < 0.001 and p = 0.006 respectively). cTp-e was found to be longer in the febrile period according to Bazett, Fridericia, and Framingham formulations (p < 0.001, p = 0.002, p < 0.001, respectively). Tp-e/QT ratio was found to be higher in the febrile period than in the afebrile period (p < 0.001).Conclusion:Although QT, cQT, and Tpe intervals were shorter, cTpe interval and Tpe/QT ratio were longer and higher in the febrile period, respectively. These findings may indicate that fever may create a proarrhythmic effect by causing variability in the transmural distribution of myocardial repolarization.

The Short QTc Is a Marker for the Development of Atrial Flutter and Atrial Fibrillation.

A short QT interval has been difficult to define, and there is debate whether it exists outside of an extremely small group of individuals with inherited channelopathies and whether it predicts cardiac arrhythmias. The objective was to identify cases with short QT and their consequences. Our hospital ECG database was screened for cases with a QTc based on the Bazett formula (QTcBZT) of less than 340 ms. The QTc was recalculated using the spline (QTcRBK) formula, which more accurately adjusts for the heart rate and identifies cases based on percentile distribution of the QT interval. The exclusion criteria were presence of bundle branch block, arrhythmias, or electronic pacemakers. An age- and sex-matched cohort was obtained from individuals with normal QT intervals with the same exclusion criteria. There were 28 cases with a short QTc (QTcRBK < 380 ms). The age was 69.6 ± 14.6 years (mean ± SD) (50% males). The QT interval was 305.7 ± 61.1 ms with QTcRBK 308.4 ± 31.4 ms. Subsequent ECGs showed atrial flutter in 21%, atrial fibrillation in 18%, and atrial tachycardia in 4% of cases. Thus, atrial arrhythmias occurred in 43% of cases. This incidence was significantly (p < 0.0001) greater than the incidence of atrial arrhythmias in age- and sex-matched controls. In conclusion, a short QT interval can be readily identified based on the first percentile of the new QTc formula. A short QTc is an important marker for the development of atrial arrhythmias, including atrial flutter and atrial fibrillation, with the former predominating. It should be part of patient assessment and warrants consideration to develop strategies for detection and prevention of atrial arrhythmias.

Short QT syndrome: The current evidences of diagnosis and management.

There are many cardiac arrhythmias and sudden cardiac death (SCD) related to channelopathies or ion channel disorders. Short QT syndrome (SQTS) is an inherited cardiac channelopathy principally caused by defective functioning of both potassium–calcium ion channel that lead to abnormal shortening of QT interval, and an increased risk of ventricular and atrial arrhythmias. Tall T waves in all lead electrocardiogram (ECG), peaked T waves, and narrow‐based T waves that are reminiscent of the typical “desert tent” T waves of hyperkalemia are frequently associated with SQTS. Diagnosis is based on patient's family history, evaluation of symptoms (palpitations and cardiac arrest), and 12‐lead ECG. It can be time challenging because of the wide range of QT interval in healthy subjects. Implantable cardioverter defibrillator (ICD) is the first‐line therapy in SQTS. Quinidine has the potential to be an effective pharmacological therapy for SQTS patients, especially in young children who are not feasible in ICD implantation, because of the ability to prolong QT interval.

Dermatomyositis Presenting as Life-threatening Hypercalcemia

Dermatomyositis is a rare disease characterized by classic skin lesions and muscle weakness. In rare cases, life-threatening hypercalcemia may develop caused by regression of dystrophic calcifications. Here we report a 36-year-old man who presented with progressive proximal weakness, difficulty in ambulation, and weight loss. He had the V-sign, Gottron’s papules, and hard, chalky nodules on both antecubital, thigh, and hip areas. Laboratory examinations revealed hypercalcemia (3.47 mmol/L) and shortened QT interval. Workup for malignancy and tuberculosis yielded negative results. Biopsy of the antecubital areas revealed calcinosis cutis. Serum calcium levels gradually normalized with hydration and steroids. Our case illustrated that a high index of suspicion for dermatomyositis is warranted for early diagnosis and ascertaining the etiology of hypercalcemia is vital in the management of this life-threatening complication. While hypercalcemia from dermatomyositis may respond to steroids, to date, individualization of treatment remains the standard of care. (J Rheum Dis 2020;27:285-289)

Does a short QT interval increase the risk of cardiac death in healthy people?

Does a short QT interval increase the risk of cardiac death in healthy people?

Antiarrhythmic Properties of Elsholtzia ciliata Essential Oil on Electrical Activity of the Isolated Rabbit Heart and Preferential Inhibition of Sodium Conductance.

Elsholtzia ciliata essential oil (E. ciliata) has been developed in Lithuania and internationally patented as exerting antiarrhythmic properties. Here we demonstrate the pharmacological effects of this herbal preparation on cardiac electrical activity. We used cardiac surface ECG and a combination of microelectrode and optical mapping techniques to track the action potentials (APs) in the Langendorff-perfused rabbit heart model during atrial/endo-/epi-cardial pacing. Activation time, conduction velocity and AP duration (APD) maps were constructed. E. ciliata increased the QRS duration and shortened QT interval of ECG at concentrations of 0.01–0.1 μL/mL, whereas 0.3 μL/mL (0.03%) concentration resulted in marked strengthening of changes. In addition, the E. ciliata in a concentration dependent manner reduced the AP upstroke dV/dtmax and AP amplitude as well as APD. A marked attenuation of the AP dV/dtmax and a slowing spread of electrical signals suggest the impaired functioning of Na+-channels, and the effect was use-dependent. Importantly, all these changes were at least partially reversible. Our results indicate that E. ciliata modulates cardiac electrical activity preferentially inhibiting Na+ conductance, which may contribute to its effects as a natural antiarrhythmic medicine.

Metformin Shortens Prolonged QT Interval in Diabetic Mice by Inhibiting L-Type Calcium Current: A Possible Therapeutic Approach.

The incidence and mortality of cardiovascular disease in diabetic patients are 2-3 times higher than those in non-diabetic patients. Abnormal function of the L-type calcium channel in myocardial tissue might result in multiple cardiac disorders such as a prolonged QT interval. Therefore, QT prolongation is an independent risk factor of cardiovascular disease in patients with diabetes mellitus. Metformin, a hypoglycemic agent, is widely known to effectively reduce the occurrence of macrovascular diseases. The aim of the present study was to evaluate the effect of metformin on prolonged QT interval and to explore potential ionic mechanisms induced by diabetes. Diabetic mouse models were established with streptozotocin and an electrocardiogram was used to monitor the QT interval after 4 weeks of metformin treatment in each group. Action potential duration (APD) and L-type calcium current (ICa-L) were detected by patch-clamp in isolated mice ventricular cardiomyocytes and neonatal cardiomyocytes of mice. The expression levels of CACNA1C mRNA and Cav1.2 were measured by real-time PCR, western blot and immunofluorescence. A shortened QT interval was observed after 4 weeks of metformin treatment in diabetic mice. Patch-clamp results revealed that both APD and ICa-L were shortened in mouse cardiomyocytes. Furthermore, the expression levels of CACNA1C mRNA and Cav1.2 were decreased in the metformin group. The same results were also obtained in cultured neonatal mice cardiomyocytes. Overall, these results verify that metformin could shorten a prolonged QT interval by inhibiting the calcium current, suggesting that metformin may play a role in the electrophysiology underlying diabetic cardiopathy.

Concomitant Treatment with Proton Pump Inhibitors and Cephalosporins Does Not Enhance QT-Associated Proarrhythmia in Isolated Rabbit Hearts.

Recent results from data mining analyses and reports of adverse drug events suggest a QT-prolonging drug-drug interaction resulting from the combination of distinct proton pump inhibitors and cephalosporins. Therefore, this study aimed at investigating the effect of the suspected QT-prolonging combinations of lansoprazole + ceftriaxone and esomeprazole + cefazolin, respectively. 26 hearts of New Zealand White rabbits were retrogradely perfused and paced at different cycle lengths. After generating baseline data, the hearts were assigned to two groups: In group 1, hearts were treated with 5µM lansoprazole. Thereafter, 200µM ceftriaxone was infused additionally. Group 2 was perfused with 10µM esomeprazole followed by 250µM cefazolin. In group 1, lansoprazole did not significantly alter QT intervals and APD90. Additional treatment with ceftriaxone significantly shortened QT interval, APD90 and slightly reduced dispersion of repolarization compared to sole lansoprazole infusion. In group 2, esomeprazole led to a significant shortening of the QT interval without altering APD90 or dispersion. Additional treatment with the antibiotic cefazolin further shortened QT interval, APD90 and reduced the dispersion of repolarization. Incidence of ventricular arrhythmias was not significantly altered in both groups. This is the first experimental whole-heart study that investigated the impact of a concomitant treatment with proton pump inhibitors and cephalosporins. In contrast to previous reports, the combination of both agents did not cause QT prolongation but instead shortened QT interval and action potential duration. As a consequence, no triggered activity occurred in the presence of a stable dispersion of repolarization.