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Charles Antzelevitch

Publications and source records attributed to Charles Antzelevitch.

At least 19 recordsLinked to original sources
PubMed2007

Loss-of-function mutations in the cardiac calcium channel underlie a new clinical entity characterized by ST-segment elevation, short QT intervals, and sudden cardiac death.

BACKGROUND: Cardiac ion channelopathies are responsible for an ever-increasing number and diversity of familial cardiac arrhythmia syndromes. We describe a new clinical entity that consists of an ST-segment elevation in the right precordial ECG leads, a shorter-than-normal QT interval, and a history of sudden cardiac death. METHODS AND RESULTS: Eighty-two consecutive probands with Brugada syndrome were screened for ion channel gene mutations with direct sequencing. Site-directed mutagenesis was performed, and CHO-K1 cells were cotransfected with cDNAs encoding wild-type or mutant CACNB2b (Ca(v beta2b)), CACNA2D1 (Ca(v alpha2delta1)), and CACNA1C tagged with enhanced yellow fluorescent protein (Ca(v)1.2). Whole-cell patch-clamp studies were performed after 48 to 72 hours. Three probands displaying ST-segment elevation and corrected QT intervals < or = 360 ms had mutations in genes encoding the cardiac L-type calcium channel. Corrected QT ranged from 330 to 370 ms among probands and clinically affected family members. Rate adaptation of QT interval was reduced. Quinidine normalized the QT interval and prevented stimulation-induced ventricular tachycardia. Genetic and heterologous expression studies revealed loss-of-function missense mutations in CACNA1C (A39V and G490R) and CACNB2 (S481L) encoding the alpha1- and beta2b-subunits of the L-type calcium channel. Confocal microscopy revealed a defect in trafficking of A39V Ca(v)1.2 channels but normal trafficking of channels containing G490R Ca(v)1.2 or S481L Ca(v beta2b)-subunits. CONCLUSIONS: This is the first report of loss-of-function mutations in genes encoding the cardiac L-type calcium channel to be associated with a familial sudden cardiac death syndrome in which a Brugada syndrome phenotype is combined with shorter-than-normal QT intervals.

Adult↗
PubMed2006

Compound heterozygous mutations P336L and I1660V in the human cardiac sodium channel associated with the Brugada syndrome.

BACKGROUND: Loss-of-function mutations in SCN5A have been associated with the Brugada syndrome. We report the first Brugada syndrome family with compound heterozygous mutations in SCN5A. The proband inherited 1 mutation from each parent and transmitted 1 to each daughter. METHODS AND RESULTS: The effects of the mutations on the function of the sodium channel were evaluated with heterologous expression in TSA201 cells, patch-clamp study, and confocal microscopy. Genetic analysis revealed that the proband carried 2 heterozygous missense mutations (P336L and I1660V) on separate alleles. He displayed a coved-type ST-segment elevation and a prolonged PR interval (280 ms). One daughter inherited P336L and exhibited a prolonged PR (210 ms). The other daughter inherited mutation I1660V and displayed a normal PR interval. Both daughters had a slightly elevated, upsloping ST-segment elevation. The parents had normal ECGs. Patch-clamp analysis showed that the P336L mutation reduced I(Na) by 85% relative to wild type. The I1660V mutation produced little measurable current, which was rescued by room temperature incubation for 48 hours. Sodium channel blockers also rescued the I1660V current, with mexiletine proving to be the most effective. Confocal immunofluorescence showed that I1660V channels conjugated to green fluorescent protein remained trapped in intracellular organelles. CONCLUSIONS: Mutation P336L produced a reduction in cardiac I(Na), whereas I1660V abolished it. Only the proband carrying both mutations displayed the Brugada syndrome phenotype, whereas neither mutation alone produced the clinical phenotype. I1660V channels could be rescued pharmacologically and by incubation at room temperature. The present data highlight the role of compound heterozygosity in modulating the phenotypic expression and penetrance of Brugada syndrome.

Brugada Syndrome↗
PubMed2006

Genetic and biophysical basis for bupivacaine-induced ST segment elevation and VT/VF. Anesthesia unmasked Brugada syndrome.

BACKGROUND: Brugada syndrome is an inherited disease associated with sudden cardiac death. The electrocardiographic pattern associated with Brugada syndrome has been linked to the use of sodium channel blockers, including antiarrhythmics, trycyclics and anesthetics. OBJECTIVE: We report a case of bupivacaine-induced Brugada syndrome, in which we investigated the genetic, biophysical and path physiological mechanism involved. METHODS AND RESULTS: The patient developed a Brugada-like electrocardiographic pattern twice under the influence of bupivacaine. The first occurrence was accompanied by ventricular tachycardia (VT) which subsided after withdrawal of the anesthetic. The VT was also observed during co-administration of diltiazem and isosorbide-5-mononitrate, agents thought to facilitate ST segment elevation in the Brugada syndrome. Genetic analysis revealed a missense mutation in the alpha subunit of the cardiac sodium channel, SCN5A. Biophysical analysis by whole-cell patch-clamping revealed a reduction in sodium current as a result of the mutation. The study of bupivacaine in the wedge model revealed use-dependent changes in conduction, heterogeneous loss of the action potential dome in RV epicardium and phase 2 re-entry when the preparations were pretreated with low concentrations of the calcium channel blocker verapamil. CONCLUSION: Our findings indicate that bupivacaine may induce the electrocardiographic and arrhythmic manifestations of the Brugada syndrome in silent carriers of SCN5A mutations. The data have important implications in the management of patients who develop ST segment elevation when under the influence of anesthetics such as bupivacaine.

Anesthesia, General↗
PubMed2006

Blinded validation of the isolated arterially perfused rabbit ventricular wedge in preclinical assessment of drug-induced proarrhythmias.

BACKGROUND: The development of preclinical models with high predictive value for the identification of drugs with a proclivity to induce Torsade de Pointes (TdP) in the clinic has long been a pressing goal of academia, industry and regulatory agencies alike. The present study provides a blinded appraisal of drugs, in an isolated arterially-perfused rabbit ventricular wedge preparation, with and without the potential to produce TdP. METHODS AND RESULTS: Thirteen compounds were tested for their potential for TdP using the rabbit left ventricular wedges. All investigators were blinded to the names, concentrations and molecular weights of the drugs. The compounds were prepared by the study sponsor and sent to the investigator as 4 sets of 13 stock solutions with the order within each set being assigned by a random number generator. Each compound was scored semi-quantitatively for its relative potential for TdP based on its effect on ventricular repolarization measured as QT interval, dispersion of repolarization measured as T(p-e)/QT ratio and early afterdepolarizations. Disclosure of the names and concentrations after completion of the study revealed that all compounds known to be free of TdP risk received a score of less or equal to 0.25, whereas those with known TdP risk received a score ranging from 1.00 to 7.25 at concentrations less than 100X their free therapeutic plasma C(max). CONCLUSIONS: Our study provides a blinded evaluation of the isolated arterially-perfused rabbit wedge preparation demonstrating both a high sensitivity and specificity in the assessment of 13 agents with varying propensity for causing TdP.

Action Potentials↗
PubMed2006

Tpeak-Tend and Tpeak-Tend dispersion as risk factors for ventricular tachycardia/ventricular fibrillation in patients with the Brugada syndrome.

OBJECTIVES: Our objective in this study was to evaluate Tpeak-Tend interval (Tp-e) and other electrocardiographic parameters as risk factors for recurrence of life-threatening cardiac events in patients with the Brugada syndrome (BS). BACKGROUND: The Tp-e interval in the electrocardiogram (ECG) has been reported to predict life-threatening arrhythmias in the long QT syndrome. METHODS: Twenty-nine patients with the ECG pattern of BS and 29 healthy age- and gender-matched controls were studied. The follow-up period was 42.65 +/- 24.42 months (range 11 to 108 months). RESULTS: Upon presentation, five patients had suffered aborted sudden death, five syncope, and two presyncope. Eleven patients with the ECG pattern of BS had a prolonged (>460 ms) QTc in V2 but usually not in inferior or left leads. No patient had abnormally prolonged QT dispersion. Programmed electrical stimulation induced ventricular tachycardia/fibrillation in 5 out of 26 patients. Inducibility did not predict recurrence of events. Cardioverter-defibrillators were implanted in 14 patients (all symptomatic and two asymptomatic). During follow-up, nine symptomatic patients experienced recurrences. Previous cardiac events and a QTc >460 ms in V2 were significant risk factors (p = 0.00002 and p = 0.03, respectively). Tp-e and Tp-e dispersion were significantly prolonged in patients with recurrences versus patients without events (104.4 and 35.6 ms vs. 87.4 and 23.2 ms; p = 0.006 and p = 0.03, respectively) or controls (90.7 and 17.9 ms; p = 0.02 and p = 0.001, respectively). CONCLUSIONS: Our study demonstrates significant correlation between previous events, QTc >460 ms in V2, Tp-e, and Tp-e dispersion and occurrence of life-threatening arrhythmic events, suggesting that these parameters may be useful in risk stratification of patients with the Brugada syndrome.

Adult↗
PubMed2006

Functional expression of "cardiac-type" Nav1.5 sodium channel in canine intracardiac ganglia.

BACKGROUND: The autonomic nervous system has been implicated in several arrhythmogenic diseases, including long QT syndrome type 3 (LQT3) and Brugada syndrome. Scarce information on the cellular components of the intrinsic cardiac ganglia from higher mammals has limited our understanding of the role of the autonomic nervous system in such diseases. OBJECTIVES: The purpose of this study was to isolate and characterize the electrophysiologic properties of canine intracardiac neurons. METHODS: Action potentials (APs) and ionic currents were studied in enzymatically dissociated canine intracardiac neurons under current and voltage clamp conditions. Immunohistochemical and reverse transcription-polymerase chain reaction analysis was performed using freshly isolated intracardiac ganglia. RESULTS: APs recorded from intracardiac neurons displayed a tetrodotoxin-resistant (TTX-R) component. TTX-R APs were abolished in the absence of sodium but persisted in the absence of external calcium. Immunohistochemical studies showed the presence of TTX-R sodium channels in these ganglia. Sodium currents were characterized by two components with different affinities for TTX: a tetrodotoxin-sensitive (TTX-S) component and a TTX-R component. TTX-S current inactivation was characteristic of neuronal sodium currents, whereas TTX-R current inactivation time constants were similar to those previously reported for Na(v)1.5 channels. TTX sensitivity (IC(50) = 1.17 microM) of the TTX-R component was in the range reported for Na(v)1.5 channels. Expression of Na(v)1.5 channels in intracardiac ganglia was confirmed by PCR analysis and sequencing. CONCLUSION: Our results suggest that canine intracardiac neurons functionally express Na(v)1.5 channels. These findings open an exciting new door to our understanding of autonomically modulated arrhythmogenic diseases linked to mutations in Na(v)1.5 channels, including Brugada syndrome and LQT3.

Action Potentials↗
PubMed2006

Contemporary definitions and classification of the cardiomyopathies: an American Heart Association Scientific Statement from the Council on Clinical Cardiology, Heart Failure and Transplantation Committee; Quality of Care and Outcomes Research and Functional Genomics and Translational Biology Interdisciplinary Working Groups; and Council on Epidemiology and Prevention.

Classifications of heart muscle diseases have proved to be exceedingly complex and in many respects contradictory. Indeed, the precise language used to describe these diseases is profoundly important. A new contemporary and rigorous classification of cardiomyopathies (with definitions) is proposed here. This reference document affords an important framework and measure of clarity to this heterogeneous group of diseases. Of particular note, the present classification scheme recognizes the rapid evolution of molecular genetics in cardiology, as well as the introduction of several recently described diseases, and is unique in that it incorporates ion channelopathies as a primary cardiomyopathy.

American Heart Association↗
PubMed2006

Dimethyl lithospermate B, an extract of Danshen, suppresses arrhythmogenesis associated with the Brugada syndrome.

BACKGROUND: Dimethyl lithospermate B (dmLSB) is an extract of Danshen, a traditional Chinese herbal remedy, which slows inactivation of INa, leading to increased inward current during the early phases of the action potential (AP). We hypothesized that this action would be antiarrhythmic in the setting of Brugada syndrome. METHODS AND RESULTS: The Brugada syndrome phenotype was created in canine arterially perfused right ventricular wedge preparations with the use of either terfenadine or verapamil to inhibit INa and ICa or pinacidil to activate IK-ATP. AP recordings were simultaneously recorded from epicardial and endocardial sites together with an ECG. Terfenadine, verapamil, and pinacidil each induced all-or-none repolarization at some epicardial sites but not others, leading to ST-segment elevation as well as an increase in both epicardial and transmural dispersions of repolarization (EDR and TDR, respectively) from 12.9+/-9.6 to 107.0+/-54.8 ms and from 22.4+/-8.1 to 82.2+/-37.4 ms, respectively (P<0.05; n=9). Under these conditions, phase 2 reentry developed as the epicardial AP dome propagated from sites where it was maintained to sites at which it was lost, generating closely coupled extrasystoles and ventricular tachycardia and fibrillation. Addition of dmLSB (10 micromol/L) to the coronary perfusate restored the epicardial AP dome, reduced EDR and TDR to 12.4+/-18.1 and 24.4+/-26.7 ms, respectively (P<0.05; n=9), and abolished phase 2 reentry-induced extrasystoles and ventricular tachycardia and fibrillation in 9 of 9 preparations. CONCLUSIONS: Our data suggest that dmLSB is effective in eliminating the arrhythmogenic substrate responsible for the Brugada syndrome and that it deserves further study as a pharmacological adjunct to implanted cardioverter/defibrillator usage.

Animals↗
PubMed2006

Electrocardiographic changes predicting sudden death in propofol-related infusion syndrome.

BACKGROUND: The occurrence of metabolic acidosis, rhabdomyolysis, hyperkalemia, and sudden cardiac death after long-term, high-dose propofol infusion has been referred to as propofol infusion syndrome (PRIS). OBJECTIVES: The purpose of this study was to explore the ECG abnormalities observed in a patient with PRIS in order to identify possible pathophysiologic mechanisms of the syndrome. METHODS: ECG changes in the index case were characterized by down-sloping ST-segment elevation in precordial leads V1 to V3 (Brugada-like ECG pattern). We subsequently assessed the relationship between this ECG pattern and the propofol infusion rate, the development of arrhythmias, and the occurrence of sudden death in a previously described cohort of 67 head-injured patients, seven of whom had been identified as having PRIS. RESULTS: Six of the PRIS patients developed the ECG pattern of ST-segment elevation in leads V1 to V3 and died within hours of irrecoverable electrical storm. This ECG pattern was the first aberration recorded hours before the death of these patients. ECGs that were available for 30 of 60 unaffected patients exhibited a normal pattern. None of the 60 patients developed ventricular arrhythmias. CONCLUSION: Our findings indicate that development of an acquired Brugada-like ECG pattern in severely head-injured patients is a sign of cardiac electrical instability that predicts imminent cardiac death. Future studies will determine whether such an ECG pattern also predicts imminent cardiac arrhythmia in other patient populations.

Acidosis↗
PubMed2006

Cellular basis for electrocardiographic and arrhythmic manifestations of Andersen-Tawil syndrome (LQT7).

BACKGROUND: Andersen-Tawil syndrome, a skeletal muscle syndrome associated with periodic paralysis and long QT intervals on the ECG, has been linked to defects in KCNJ2, the gene encoding for the inward rectifier potassium channel (I(K1).) OBJECTIVES: The purpose of this study was to examine the cellular mechanisms underlying the ECG and arrhythmic manifestations of Andersen-Tawil syndrome. METHODS: To investigate the effects of KCNJ2 loss-of-function mutations responsible for Andersen-Tawil syndrome, we used barium chloride (BaCl(2)) to inhibit I(K1) in arterially perfused wedge preparation. Transmembrane action potentials (APs) were simultaneously recorded from endocardial, midmyocardial, and epicardial cells, together with a transmural ECG. RESULTS: BaCl(2) (1 to 30 microM) produced a concentration-dependent prolongation of the QT interval, secondary to a homogeneous prolongation of AP duration of the three cell types. QT interval was prolonged without an increase in transmural dispersion of repolarization (TDR). Low extracellular potassium (2.0 mM), isoproterenol (20-50 nM), and an abrupt increase in temperature (36 degrees C-39 degrees C) in the presence of 10 microM BaCl(2) did not significantly increase TDR but increased ectopic extrasystolic activity. Early afterdepolarizations were not observed under any condition. Spontaneous torsades de pointes arrhythmias were never observed, nor could they be induced with programmed electrical stimulation under any of the conditions studied. CONCLUSION: Our results provide an understanding of why QT prolongation associated with Andersen-Tawil syndrome is relatively benign in the clinic and provide further support for the hypothesis that the increase in TDR, rather than QT interval, is responsible for development of torsades de pointes.

Action Potentials↗
PubMed2006

Late-phase 3 EAD. A unique mechanism contributing to initiation of atrial fibrillation.

Early (EAD) and delayed (DAD) afterdepolarizations-induced triggered activity is capable of initiating and maintaining cardiac arrhythmias. EAD-induced triggered responses are traditionally thought to be involved in the generation of ventricular arrhythmias under long QT conditions and are precipitated by bradycardia or long pauses. In contrast, DAD-induced triggered activity commonly underlies arrhythmias precipitated by tachycardia. Spontaneous release of calcium from the sarcoplasmic reticulum (SR) secondary to cellular calcium overload induces DADs and some forms of EADs. Recent studies from our laboratory have uncovered a novel mechanism giving rise to triggered activity, termed "late-phase 3 EAD," which combines properties of both EAD and DAD, but has its own unique character. Late-phase 3 EAD-induced triggered extrasystoles represent a new concept of arrhythmogenesis in which abbreviated repolarization permits "normal SR calcium release" to induce an EAD-mediated closely coupled triggered response, particularly under conditions permitting intracellular calcium loading. This review briefly describes the mechanisms and properties of late-phase 3 EADs, how they differ from conventional EADs and DADs, as well as their role in the initiation of cardiac arrhythmias, such as atrial fibrillation.

Action Potentials↗
PubMed2006

Brugada syndrome.

First introduced as a new clinical entity in 1992, the Brugada syndrome is associated with a relatively high risk of sudden death in young adults, and occasionally in children and infants. Recent years have witnessed a striking proliferation of papers dealing with the clinical and basic aspects of the disease. Characterized by a coved-type ST-segment elevation in the right precordial leads of the electrocardiogram (ECG), the Brugada syndrome has a genetic basis that thus far has been linked only to mutations in SCN5A, the gene that encodes the alpha-subunit of the sodium channel. The Brugada ECG is often concealed, but can be unmasked or modulated by a number of drugs and pathophysiological states including sodium channel blockers, a febrile state, vagotonic agents, tricyclic antidepressants, as well as cocaine and propranolol intoxication. Average age at the time of initial diagnosis or sudden death is 40 +/- 22, with the youngest patient diagnosed at 2 days of age and the oldest at 84 years. This review provides an overview of the clinical, genetic, molecular, and cellular aspects of the Brugada syndrome, incorporating the results of two recent consensus conferences. Controversies with regard to risk stratification and newly proposed pharmacologic strategies are discussed.

Brugada Syndrome↗
PubMed2006

The role of sodium channel current in modulating transmural dispersion of repolarization and arrhythmogenesis.

Ventricular myocardium in larger mammals is composed of three distinct cell types: epicardial, M, and endocardial cells. Epicardial and M cell, but not endocardial cell, action potentials have a prominent I(to)-mediated notch. M cells are distinguished from the other cell types in that they display a smaller I(Ks), but a larger late I(Na) and I(Na-Ca). These ionic differences may account for the longer action potential duration (APD) and steeper APD-rate relationship of the M cell. The difference in the time course of repolarization of phase 1 and phase 3 contributes to the inscription of the electrocardiographic J wave and T wave, respectively. These repolarization gradients are modulated by electrotonic interactions, [K(+)](o), and agents or mutations that alter net repolarizing current. An increase in late I(Na), as occurring under a variety of pathophysiological states or in response to certain toxins, leads to a preferential prolongation of the M cell action potential, thus prolonging the QT interval and increasing transmural dispersion of repolarization (TDR), which underlies the development of torsade de pointes (TdP) arrhythmias. Agents that reduce late I(Na) are effective in reducing TDR and suppressing TdP. A reduction in peak I(Na) or an increase in net repolarizing current in the early phases of the action potential can lead to a preferential abbreviation of the action potential of epicardium in the right ventricle, and thus the development of a large TDR, phase 2 reentry, and polymorphic ventricular tachycardia associated with the Brugada syndrome.

Action Potentials↗
PubMed2006

Cellular basis for the repolarization waves of the ECG.

One hundred years after Willem Einthoven first recorded the electrocardiogram (ECG), physicians and scientists are still debating the cellular basis for the various waves of the ECG. In this review, our focus is on the cellular basis for the J, T, and U waves of the ECG. The J wave and T wave are thought to arise as a consequence of voltage gradients that develop as a result of the electrical heterogeneities that exist within the ventricular myocardium. The presence of a prominent action potential notch in epicardium but not endocardium gives rise to a voltage gradient during ventricular activation that inscribes the J wave. Transmural and apico-basal voltage gradients developing as a result of difference in the time course of repolarization of the epicardial, M, and endocardial cell action potentials, and the more positive plateau potential of the M cell contribute to inscription of the T wave. Amplification of these heterogeneities results in abnormalities of the J wave and T wave, leading to the development of the Brugada, long QT, and short QT syndromes. The basis for the U wave has long been a matter of debate. One theory attributes the U wave to mechanoelectrical feedback. A second theory ascribes it to voltage gradients within ventricular myocardium and a third to voltage gradients between the ventricular myocardium and the His-Purkinje system. Although direct evidence in support of any of these three hypotheses is lacking, recent studies involving the short QT syndrome have generated renewed interest in the mechanoelectrical hypothesis.

Animals↗
PubMed2005

Potential proarrhythmic effects of biventricular pacing.

Resynchronization therapy involving right ventricular endocardial and left ventricular epicardial pacing improves cardiac output, quality of life, and New York Heart Association functional class in patients with congestive heart failure. Although a great deal of attention has been directed at showing the mechanical benefits and in fine-tuning the biventricular pacing configuration and protocol, little attention has been focused on the consequences of reversing the direction of activation of the left ventricular wall. Recent basic science and clinical studies have shown a proarrhythmic effect of reversing the direction of activation of the left ventricular wall. Reversal of the normal activation sequence prolongs the QT interval and increases the existing transmural dispersion of repolarization, creating the substrate and trigger for re-entrant arrhythmias under long QT conditions. A number of case reports of R-on-T extrasystoles and ventricular tachyarrhythmia induction as a result of biventricular pacing support this observation, and raise concern that biventricular pacing may be proarrhythmic in select cases, particularly when associated with a prolonged QT interval. Our focus in this review is on current understanding of transmural heterogeneity of repolarization that exists across the left ventricular wall, how this dispersion of repolarization is amplified as a consequence of reversal of the normal activation sequence, and how these basic experimental findings may apply to patients receiving cardiac resynchronization therapy.

Animals↗
PubMed2005

The homeodomain transcription factor Irx5 establishes the mouse cardiac ventricular repolarization gradient.

Rhythmic cardiac contractions depend on the organized propagation of depolarizing and repolarizing wavefronts. Repolarization is spatially heterogeneous and depends largely on gradients of potassium currents. Gradient disruption in heart disease may underlie susceptibility to fatal arrhythmias, but it is not known how this gradient is established. We show that, in mice lacking the homeodomain transcription factor Irx5, the cardiac repolarization gradient is abolished due to increased Kv4.2 potassium-channel expression in endocardial myocardium, resulting in a selective increase of the major cardiac repolarization current, I(to,f), and increased susceptibility to arrhythmias. Myocardial Irx5 is expressed in a gradient opposite that of Kv4.2, and Irx5 represses Kv4.2 expression by recruiting mBop, a cardiac transcriptional repressor. Thus, an Irx5 repressor gradient negatively regulates potassium-channel-gene expression in the heart, forming an inverse I(to,f) gradient that ensures coordinated cardiac repolarization while also preventing arrhythmias.

Action Potentials↗
PubMed2005

Provocation of sudden heart rate oscillation with adenosine exposes abnormal QT responses in patients with long QT syndrome: a bedside test for diagnosing long QT syndrome.

AIMS: As arrhythmias in the long QT syndrome (LQTS) are triggered by heart rate deceleration or acceleration, we speculated that the sudden bradycardia and subsequent tachycardia that follow adenosine injection would unravel QT changes of diagnostic value in patients with LQTS. METHODS AND RESULTS: Patients (18 LQTS and 20 controls) received intravenous adenosine during sinus rhythm. Adenosine was injected at incremental doses until atrioventricular block or sinus pauses lasting 3 s occurred. The QT duration and morphology were studied at baseline and at the time of maximal bradycardia and subsequent tachycardia. Despite similar degree of adenosine-induced bradycardia (longest R-R 1.7+/-0.7 vs. 2.2+/-1.3 s for LQTS and controls, P=NS), the QT interval of LQT patients increased by 15.8+/-13.1%, whereas the QT of controls increased by only 1.5+/-6.7% (P<0.001). Similarly, despite similar reflex tachycardia (shortest R-R 0.58+/-0.07 vs. 0.55+/-0.07 s for LQT patients and controls, P=NS), LQTS patients developed greater QT prolongation (QTc=569+/-53 vs. 458+/-58 ms for LQT patients and controls, P<0.001). The best discriminator was the QTc during maximal bradycardia. Notched T-waves were observed in 72% of LQT patients but in only 5% of controls during adenosine-induced bradycardia (P<0.001). CONCLUSION: By provoking transient bradycardia followed by sinus tachycardia, this adenosine challenge test triggers QT changes that appear to be useful in distinguishing patients with LQTS from healthy controls.

Adenosine↗