Severe QT Prolongation Research Articles

Long QT Syndrome

A 34-year-old female who is 4 months postpartum presents after a nocturnal seizure. She was awakened at night by an alarm clock to feed her baby, spoke briefly with her husband, and suddenly lost consciousness, appearing to have epileptic-type movements before spontaneously recovering. On further questioning, she reported several syncopal events over the past 15 years, once when standing suddenly, also thought at the time to be a seizure. Previous neurological investigations were normal. A 12-lead ECG (Figure 1A) revealed a corrected QT interval of 550 ms with low-amplitude, notched T-waves. Figure 1. Electrocardiographic traces from leads II and V5 ( A , C–F ) and lead II ( B ) in patients with long QT syndrome. A , ECG traces from the initial patient described showing low-amplitude, notched T-waves characteristic of LQT2. B , Alternating T-wave axis and morphology (T-wave alternans) leading to an episode of torsades de pointes (TdP) triggered by a ventricular ectopic beat. C , Traces from a previously asymptomatic individual who suffered significant QT prolongation (QTc 570 ms) and ventricular fibrillation following a head injury and intracranial hemorrhage. D , On recovery his QT interval normalized (QTc 440 ms), but ( E ) showed marked prolongation 2 minutes into recovery on exercise testing (QTc 550 ms). Genetic analysis identified deletion of 10 amino acid residues in KCNQ1 . F , Severe QT prolongation (QTc 740 ms) in a 9-year-old child presenting with nocturnal seizures. Despite propranolol therapy he continued to have short runs of TdP and underwent primary prevention ICD implantation. A functionally deleterious missense mutation previously associated with severe phenotype was identified in SCN5A (c.G1231A; p.V411M). Long QT syndrome (LQTS) is an inherited cardiac condition caused by genetically encoded abnormalities in cardiac ion channels, characterized clinically by palpitations, syncope, and sudden cardiac death, with varying degrees of QT prolongation and T-wave morphological …

Vital Signs, QT Prolongation, and Newly Diagnosed Cardiovascular Disease During Severe Hypoglycemia in Type 1 and Type 2 Diabetic Patients

OBJECTIVE To assess vital signs, QT intervals, and newly diagnosed cardiovascular disease during severe hypoglycemia in diabetic patients. RESEARCH DESIGN AND METHODS From January 2006 to March 2012, we conducted a retrospective cohort study to assess type 1 and type 2 diabetic patients with severe hypoglycemia at a national center in Japan. Severe hypoglycemia was defined as the presence of any hypoglycemic symptoms that could not be resolved by the patients themselves in prehospital settings. RESULTS A total of 59,602 cases that visited the emergency room by ambulance were screened, and 414 cases of severe hypoglycemia were analyzed. The median (interquartile range) blood glucose levels were not significantly different between the type 1 diabetes mellitus (T1DM) (n = 88) and type 2 diabetes mellitus (T2DM) (n = 326) groups (32 [24-42] vs. 31 [24-39] mg/dL, P = 0.59). During severe hypoglycemia, the incidences of severe hypertension (≥180/120 mmHg), hypokalemia (<3.5 mEq/L), and QT prolongation were 19.8 and 38.8% (P = 0.001), 42.4 and 36.3% (P = 0.30), and 50.0 and 59.9% (P = 0.29) in the T1DM and T2DM groups, respectively. Newly diagnosed cardiovascular disease during severe hypoglycemia and death were only observed in the T2DM group (1.5 and 1.8%, respectively). Blood glucose levels between the deceased and surviving patients in the T2DM group were significantly different (18 [14-33] vs. 31 [24-39] mg/dL, P = 0.02). CONCLUSIONS T1DM and T2DM patients with severe hypoglycemia experienced many critical problems that could lead to cardiovascular disease, fatal arrhythmia, and death.

Serum concentration of eperisone hydrochloride correlates with QT interval

BackgroundEperisone hydrochloride is a centrally acting muscle relaxant prescribed for muscle stiffness that acts by depressing the activities of α and γ efferent neurons in the spinal cord and supraspinal structures. Although a case of eperisone-induced severe QT prolongation had been reported, the relationship between serum eperisone concentration and QT interval remains obscure. ObjectiveThe aim of this study was to investigate the relationship between serum eperisone concentration and QT interval. MethodsFour patients who overdosed on eperisone were admitted to our hospital between January 2010 and December 2011. We took simultaneous serial measurements of serum eperisone concentration and QT interval in the intensive care unit. In total, 22 measurement points were plotted for these patients. We analyzed the correlation between the serum eperisone concentration and corrected QT (QTc) interval. ResultsThree men and one woman (mean age, 50 years) overdosed on eperisone with an average dose of 3087.5 mg (therapeutic dose, 150 mg/day). The mean QTc interval at arrival was 592 ms (range, 444–825 ms), and the mean serum eperisone concentration at arrival was 1257.5 ng/mL (range, 14.5–4120.0 ng/mL). The correlation coefficient was 0.833 between serum eperisone concentration and QTc interval (P < .001). ConclusionSerum eperisone concentration correlates with QTc interval in patients who overdose on eperisone.

The impact of drug-related QT prolongation on FDA regulatory decisions

The impact of drug-related QT prolongation on FDA regulatory decisions

Computational Predictions of Tissue-Specific Consequences of Long QT Mutations: Role of the Purkinje Fiber

The long QT syndrome (LQTS) is a heritable cardiac disorder that leads to prolongation of ventricular repolarization, episodes of ventricular arrhythmia, and sudden cardiac death. Mounting evidence has implicated the Purkinje fiber (PF) conduction system in the genesis of ventricular arrhythmias. This study assesses for tissue-specific consequences of the biophysical alterations induced by LQTS-related mutations, using computational models of ventricular and PF cells. Mutations causing LQT1 and LQT2 (in KCNQ1 and HERG, respectively) are first simulated by reducing density of the respective components of the delayed rectifier current. These mutations prolong action potential duration (APD) in ventricular myocytes more than in their PF counterparts, due to differences in the conductance and activation of plateau potassium currents between the two cell types. Next, the canonical LQT3 mutation delKPQ (in the cardiac NaV 1.5 sodium channel, encoded by SCN5A) is modeled in both tissue types (as described previously, by increasing entry into a bursting mode of channel gating, producing substantial late non-inactivating inward current). Marked APD prolongation is confirmed in both tissue types, exacerbated by slow stimulation rates or pauses in pacing. Simulation of another SCN5A mutation, F1473C, which clinically produces severe QT prolongation and heavy arrhythmia burden, is shown to have a markedly larger effect on PF cells than ventricular myocytes (including a propensity for repetitive early afterdepolarizations), owing to a depolarizing shift in the mutant channel availability and lower plateau potential in PF. Finally, the interactions between PF and ventricular cells at the tissue level are investigated in the context of these mutations in a cable model representing a section of ventricular wall. In conclusion, the biophysical alterations induced by LQT mutations may have significant tissue-specific consequences, with important implications for arrhythmia and its therapy.

Fragmented QRS is associated with torsades de pointes in patients with acquired long QT syndrome

Acquired long QT syndrome (LQTS) is a disease due to a secondary repolarization abnormality induced by various predisposing factors. In contrast to congenital LQTS, risk factors that produce acquired LQTS include organic heart diseases that often exhibit depolarization abnormality. Although various repolarization parameters have been evaluated in acquired LQTS, the existence of depolarization abnormality in association with torsades de pointes (TdP) has not been reported. The purpose of this study was to evaluate both repolarization (QT components) and depolarization parameters (fragmented QRS [fQRS]) in acquired LQTS patients with markedly prolonged QT interval. Seventy patients with acquired severe QT prolongation (QTc ≥ 550 ms) were studied. Thirty-two patients had syncope or TdP (syncope group). Thirty-eight patients did not have any symptoms (asymptomatic group). The existence of fQRS and QT components (QT, QTc, Tpe [interval between peak and end of T wave] intervals, and U-wave voltage) was analyzed. The syncope group had more frequent fQRS (81%) than did the asymptomatic group (21%, P < .01) and the incidence of fQRS was not different before and after removal of predisposing factors. The incidence of organic heart disease was not different between the two groups. No differences in QTc interval were noted between the syncope and asymptomatic groups, although the syncope group had longer QT and Tpe intervals and higher U wave than the asymptomatic group (P < .01). Acquired predisposing factors promoted repolarization abnormality (especially prolongation of QT and Tpe intervals), and the existence of fQRS had an important role in the development of TdP in patients with acquired LQTS.

A case of torsades de pointes induced by severe QT prolongation after an overdose of eperisone and triazolam in a patient receiving nifedipine

Introduction. Eperisone hydrochloride is a centrally acting muscle relaxant, and triazolam is a short-acting benzodiazepine. Although commonly prescribed, cardiotoxicity induced by a single overdose of either drug is comparatively rare. A patient receiving nifedipine developed torsades de pointes (TdP) because of prolongation of the corrected QT (QTc) interval after an overdose of eperisone hydrochloride and triazolam. Case report. A 60-year-old man receiving nifedipine was admitted in a comatose condition 3 h after ingesting 5,000 mg of eperisone and 2.5 mg of triazolam. Electrocardiogram showed sinus rhythm with prolongation of the QTc interval (820 ms). The serum electrolyte levels were as follows: potassium, 3.8 mEq/L; magnesium, 2.4 mg/dL. The serum drug concentrations were high: eperisone, 15,360 ng/mL; triazolam, 110.8 ng/mL. A temporary cardiac pacemaker was implanted immediately after the development of TdP, 11 h after the ingestion. The serum triazolam concentration normalized on day 2. The QTc interval and eperisone concentration normalized on day 6. Conclusion. Eperisone and triazolam overdose can cause life-threatening cardiotoxicity. Electrocardiographic monitoring and serial determination of QTc interval are likely the best way to observe these patients and evaluate the risk of cardiotoxicity.

Syndactyly and long QT syndrome (Ca V1.2 missense mutation G406R) is associated with hypertrophic cardiomyopathy

ong QT syndrome (LQTS) is a heterogeneous ion channel isorder caused by mutations in either the cardiac potassium hannel genes or the cardiac sodium channel gene SCN5A. anifestations of LQTS during fetal or neonatal life are ncommon and usually indicate a severe form of the disase. A specific cardiac L-type calcium channel dysfuncion has been reported to cause LQTS and syndactyly. This isorder, also called Timothy syndrome, is caused by the de ovo CaV1.2 missense mutation G406R. It appears to be a ultiorgan disease that includes congenital heart disease, ecurrent infections, hypoglycemia, and autism. The synrome is characterized by severe QT prolongation and lethal entricular arrhythmias in the first years of life. In this eport, we describe two neonates with Timothy syndrome nd extend the phenotype to include hypertrophic cardioyopathy and ventricular systolic dysfunction.

Isolated T wave alternans

Two patients with isolated T wave alternans are reported, with their vectocardiograms, their response to carotid sinus stimulation, and the response to calcium infusion in one of them with documented severe hypocalcemia. Eleven cases of the literature are briefly reviewed. The alternans of the T wave appears with severe QT prolongation, QT alternans, and an increased tendency to ventricular fibrillation. The findings are consistent with the hypothesis that T wave alternans may be the electrocardiographic manifestation of the transmembrane action potential alternans and could be related in some cases to hypocalcemia.