His-ventricular Interval Research Articles

Recruitment of bundle branches with permanent His bundle pacing in a patient with advanced conduction system disease: What is the mechanism?

The patient was a 69-year-old man with coronary artery disease who presented with syncope. His electrocardiogram showed sinus rhythm with a first-degree atrioventricular block, right bundle branch block (RBBB), and left anterior fascicular block (LAFB), and he was referred for an electrophysiology (EP) study. Baseline electrograms suggested intra-Hisian conduction disease, with split His potentials, H′ and H, and an intra-Hisian interval of 78 ms (Figure 1A). It was difficult to maintain His catheter stability during the EP study, and only the distal His signal (H) was consistent, with an His-ventricular (HV) interval of 70 ms (Figure 1A). Decremental atrial pacing demonstrated progressive rate-related HV prolongation up to 280 ms, beyond which HV Wenckebach block occurred (Figure 1B). No arrhythmias were induced with programmed atrial or ventricular stimulation. Given the evidence of infranodal AV conduction disease with probable intra-Hisian disease, we decided to implant a pacemaker. Pacing from the proximal His bundle (HB) position with the His catheter resulted in a wide QRS complex (duration 164 ms) with RBBB/LAFB and a long stimulus-QRS interval, whereas pacing at the distal HB resulted in a narrower QRS using a pacing output of 5 mA at 2 ms (threshold). Given narrowing of the QRS with distal HB pacing, we decided to implant the ventricular lead in the HB region. Unipolar recordings from the tip electrode of a 3830 pace-sense lead (3830, Medtronic Inc., Minneapolis, MN) were used to map the HB region. As seen in Figure 2, recordings from the proximal HB reveal a large A with an HV interval of 64 ms, while recordings from the distal HB reveal a far-field atrial electrogram (A) with a shorter HV interval of 46 ms. Pacing at the distal HB (distal to the site of block/delay resulting in RBBB/LAFB) resulted in para-Hisian (nonselective HB) capture (His + V), evidenced by a narrow QRS of duration 124 ms and presence of a slurred upstroke indicating local myocardial capture. The threshold of para-Hisian capture was 0.5 V at 0.5 ms. The lead was implanted in the distal HB location. What is the mechanism of narrowing of the QRS complex by permanent HB pacing in this patient with conduction disease characterized by RBBB and LAFB? Figure 2Proximal and distal His bundle (HB) recordings (paper speed 50 mm/s) and paced QRS morphology using permanent His bundle lead (3830, Medtronic). A = atrial electrogram; H = His electrogram; V = local ventricular electrogram. View Large Image Figure Viewer Download Hi-res image

Verapamil-Sensitive Upper Septal Idiopathic Left Ventricular Tachycardia: Prevalence, Mechanism, and Electrophysiological Characteristics

ObjectivesThis study sought to demonstrate the prevalence, mechanism, and electrocardiographic and electrophysiological characteristics of upper septal idiopathic left fascicular ventricular tachycardia (US-ILVT). BackgroundILVT is classified into left anterior and posterior types with no clear data about US-ILVT. MethodsAmong 193 ILVT patients, we identified 12 patients (6.2%; age 41 ± 22 years, 7 men) with US-ILVT. ResultsOf 12 patients with US-ILVT, 6 patients (50%) had previous history of radiofrequency catheter ablation for common ILVT. Sustained VT (cycle length: 349 ± 53 ms) was seen in all patients with a QRS interval slightly wider (104 ± 18 ms) than that during sinus rhythm (90 ± 19 ms). The VT exhibited an identical QRS configuration as sinus rhythm in 6 (50%) and incomplete right bundle branch block configuration in another 6. His-ventricular interval during VT was always shorter than that during sinus rhythm (27 ± 5 ms vs. 47 ± 10 ms). Purkinje potentials were activated in a reverse direction to that of common ILVT; namely, the diastolic potential (P1) was activated retrogradely but the pre-systolic potential (P2) was activated antegradely. At the left upper-middle ventricular septum, P1 potential was recorded during VT, preceding the QRS by 54 ± 20 ms. Radiofrequency catheter ablation at that site eliminated the VT with no recurrence during a 58 ± 35 months of follow-up. ConclusionsUS-ILVT is an identifiable VT that shares common criteria with ILVT and has a narrow QRS interval. Some US-ILVT cases appeared after common ILVT ablation. It is a reverse type of common ILVT (orthodromic form) with baseline morphological abnormalities that might provide a potential substrate for such VT.

Abstract 182: Characterization of Electrophysiological and Conduction Parameters of the Heart in Trpm4-deficient Mice

TRPM4 is a Ca2+-activated non-selective cation channel that belongs to the family of the Transient Receptor Potential (TRP) ion channels. Importantly, TRPM4 is impermeable for Ca2+ and is involved in different Ca2+-dependent cell functions, such as exocytosis, contraction and cell death. Trpm4 is known to be expressed in atrial and ventricular cardiomyocytes. The interest in the functional role of TRPM4 in the heart has risen further by the discovery of Trpm4 mutations that are linked to cardiac conduction disorders, including Progressive Familial Heart Block type I (PFHBI) and Brugada Syndrome. Both gain-of-function and loss-of-function mutation were described in patients with cardiac conduction diseases. Recently, our group showed that TRPM4 plays a role during the late repolarization phase of the action potential in murine ventricular cardiomyocytes and that deletion of the Trpm4 gene leads to shorter ventricular action potentials. To characterize if deletion of Trpm4 has an effect on the conduction properties of the heart, an in depth electrophysiological study was performed in living mice. An octapolar catheter was inserted into the right atrium and ventricle of the heart to measure intracardial electrograms. The atrial-His (AH) and His-ventricular (HV) intervals were calculated and no differences were found between WT and Trpm4-deficient mice. Additionally, more detailed conduction parameters of the heart were determined by use of programmed electrical stimulation (PES) protocols. Sinus node recovery time (SNRT) was not different between WT and Trpm4-deficient mice. Effective refractory period of atrium (AERP), AV node (AVNERP) and ventricle (VERP) were in the same range in WT and Trpm4-deficient mice. Wenckebach periodicity, the parameter for AV nodal conduction, was also not different between WT and Trpm4-deficient mice. These results suggest that deletion of Trpm4 has no effects on the conduction properties of the murine heart.

Combined actions of ivabradine and ranolazine reduce ventricular rate during atrial fibrillation.

Ventricular rate during atrial fibrillation (AF) can be reduced by slowing atrioventricular (AV) node conduction and/or by decreasing dominant frequency of AF. We investigated whether combined administration of ivabradine and ranolazine reduces ventricular rate during AF. Ivabradine (maximum clinical dose, 0.25 mg/kg, and 0.10 mg/kg, i.v.) and ranolazine (2.4 mg/kg, i.v., bolus followed by 0.135 mg/kg/min) were studied in an anesthetized pig (N = 16) model of AF. Combined administration of 0.25 mg/kg ivabradine with ranolazine reduced ventricular rate during AF by 51.9 ± 9.7 beats/min (23%, P = 0.017) and dominant frequency of AF by 2.8 ± 0.5 Hz (32%, P = 0.005). It increased PR (P = 0.0002, P = 0.0007) and A-H intervals (P = 0.047, P = 0.002) during pacing at 130 and 180 beats/min, respectively, to a greater degree than additive effects of single agents. Combined administration of 0.1 mg/kg ivabradine with ranolazine exceeded additive effects of single agents on A-H intervals and dominant frequency of AF. Moreover, ranolazine potentiated low-dose ivabradine's reduction in ventricular rate, as combined administration more than doubled effects of the higher ivabradine dose alone and was similar to the combination with the higher dose. Neither drug nor their combination affected contractility (left ventricular [LV] dP/dt), QT or His-ventricular (H-V) intervals, or mean arterial pressure during sinus rhythm or AF. Combined administration of ivabradine and ranolazine at clinically safe levels decreases ventricular rate during AF by reducing AV node conduction and AF dominant frequency without QT prolongation or depression in contractility. Targeting these actions offers intrinsic advantages over conventional nodal agents, which can reduce contractility.

Ablative Instincts in a 22-year-old patient with a delta wave and syncope

A 22-year-old male experienced a presyncopal spell while studying for a university examination. The symptoms disappeared within a minute. On assessment in the emergency room, a 12-lead electrocardiogram (ECG) showed a delta wave suggestive of the presence of an accessory pathway (fig. 1). Transthoracic echocardiography was performed and did not detect any structural anomalies. The patient was referred for an electrophysiological study and elective radiofrequency catheter ablation of the accessory pathway (AP). Catheters were placed in the high right atrium (HRA), the His bundle (His), the right ventricular apex (RVA) and the coronary sinus (CS). Baseline cycle length in sinus rhythm, atrial-His (AH) and His-ventricular (HV) intervals were 866, 62 and 10 ms, respectively. Ventriculoatrial conduction was present at baseline with decremental conduction properties on incremental pacing and with the earliest retrograde atrial

Predictors of Advanced His-Purkinje Conduction Disturbances in Patients With Unexplained Syncope and Bundle Branch Block

BackgroundFor patients presenting with syncope and bundle branch block (BBB), results during electrophysiological studies (EPS) might depend on the electrocardiographic pattern of conduction disturbances. We sought to identify predictors of advanced His-Purkinje conduction disturbances (HPCDs) in these patients. MethodsIn this retrospective multicentre study, patients were included who: (1) presented with unexplained syncope; (2) had BBB (QRS duration ≥ 120 ms); and (3) were investigated with EPS. HPCD was diagnosed if the baseline His-ventricular interval was ≥ 70 ms or if second- or third-degree His-Purkinje block was observed during atrial pacing or pharmacological challenge. ResultsOf the 171 patients studied (72 ± 13 years, 64% male sex, mean left ventricular ejection fraction 57 ± 9%), advanced HPCD was found in 73 patients (43%). The following electrocardiographic features were associated with HPCD (P = 0.01): isolated right BBB (34.4%), right BBB with left anterior fascicular block (36.4%), left BBB (46.2%), and right BBB with left posterior fascicular block (LPFB, 78.6%). Multivariate analysis identified first-degree atrioventricular block (odds ratio, 2.4; 95% confidence interval, 1.2-4.7; P = 0.01) and LPFB (odds ratio, 4.8; 95% confidence interval, 1.3-18.5; P = 0.02) as the only 2 independent predictors of advanced HPCD. ConclusionsFor patients presenting with syncope and BBB, first-degree atrioventricular block and LPFB increased the likelihood of finding HPCDs during EPS. However, no single electrocardiographic feature could consistently predict the outcome of EPS, so this investigation is still necessary in assessing the need for pacemaker implantation, irrespective of the precise appearance of abnormalities on ECG.

Supraventricular tachycardia termination after atrial noncapture: What is the mechanism?

A 63-year-old man with a history of palpitations presented for electrophysiology study. Multipolar catheters were placed in the right atrium, His bundle region, right ventricle, and coronary sinus (CS), with the proximal CS electrode positioned at the CS ostium. Normal atrial-His and His-ventricular intervals were recorded during sinus rhythm.

Characterization of the distal insertion of atriofascicular accessory pathways and mechanisms of QRS patterns in atriofascicular antidromic tachycardia

The distal insertion of right atriofascicular pathways remains a source of debate. Moreover, there are various morphologies of preexcited QRS complexes involving atriofascicular pathways that have been poorly characterized. To characterize the distal insertion of atriofascicular accessory pathways and to provide a mechanism for the change in QRS morphology observed between short and long ventriculo-His (V-H) antidromic atrioventricular reentrant tachycardias (AVRTs) in the same patient. Thirteen patients with atriofascicular pathways and preexcited AVRT with short V-H and long V-H intervals were studied. For each patient, the tachycardia cycle length, V-H interval, QRS width, and axis were compared. A baseline His-ventricular interval was also recorded. The baseline His-ventricular interval was significantly longer than the V-H interval during antidromic AVRT (median 50 ms vs. 10 ms; P < .0001). Retrograde right bundle branch block increased the V-H interval (median 10 ms vs. 85 ms; P < .0001), the tachycardia cycle length (median of 302.5 ms vs. 350 ms; P < .0001), and the QRS width (median 120 ms vs. 140 ms; P < .0002). At least subtle changes in QRS morphology, axis, or QRS width were seen in all patients. The distal insertion of right atriofascicular pathways fuses with the right bundle branch. The various QRS morphologies seen during the change from short V-H to long V-H antidromic AVRT can be explained by fusion, particularly over the left anterior fascicle.

Two Cases of Supraventricular Tachycardia After Accessory Pathway Ablation

A 52-year-old man was referred for recurrent palpitations after 2 prior electrophysiology studies and ablations at an outside institution targeting right anteroseptal and left posterolateral accessory pathways (AP) for orthodromic reentrant tachycardia (ORT). Baseline ECG revealed sinus rhythm without preexcitation and an incomplete right bundle branch block. An ECG from his most recent tachycardia episode demonstrated a long RP tachycardia, with an incomplete right bundle branch block pattern at a rate of 135 beats per minute. Prior echocardiogram showed no evidence of structural heart disease. At electrophysiology study, the baseline atrial-His (AH) and His-ventricular (HV) intervals were both 58 ms. There was no preexcitation with incremental atrial pacing. There were spontaneous echo beats, which had a ventriculoatrial (VA) interval of 230 ms with concentric-appearing retrograde activation. Tachycardia with a cycle length (CL) of 460 ms was reproducibly initiated with programmed ventricular stimulation after a retrograde VA jump. Entrainment from the right ventricle (RV; mid-septum) showed a V-A-V response and a postpacing interval (PPI) of 583 ms without significant AH prolongation (Figure 1). Stim-A minus V-A time was 97 ms. Premature ventricular complexes (PVCs) from the septum during tachycardia advanced the atrium only if they were delivered ≥45 ms before the His deflection. Differential pacing was performed with entrainment from the RV apex yielding a PPI of 605 ms, whereas RV basal pacing resulted in a PPI of 601 ms. PPI from the proximalcoronary sinus (CS) was markedly prolonged (>50 ms over tachycardia CL) and was even longer from the mid CS (Figure 2). Mapping of the annular septum showed earliest retrograde activation at the mid right atrial (RA) septum. PPI with entrainment from here was 20 ms >tachycardia CL. What is the mechanism of the tachycardia, and what is the appropriate next step? Figure 1. Response to entrainment from the mid-right ventricular …

Paradoxical response during para-Hisian pacing

A 21-year-old man underwent electrophysiology study for recurrent palpitation and documented narrow complex tachycardia. The baseline 12-lead electrocardiogram showed sinus rhythm with intermittent preexcitation and positive delta waves in all precordial leads, inferior leads, and lead I. The sinus cycle length and atrio-His and His-ventricular intervals were 662, 70, and 37 ms (non-preexcited beat), respectively (Figure 1). Ventricular pacing showed concentric, nondecremental ventriculoatrial (VA) conduction.

Narrow QRS complex tachycardia: What is the mechanism?

A 30-year-old woman with a history of atrioventricular nodal reentrant tachycardia (AVNRT) who underwent slow pathway modification at the age of 12 years presented with recurrent palpitations and presyncope for 1 year. She was found to have recurrent supraventricular tachycardia sensitive to adenosine and was referred for electrophysiology study and catheter ablation. Baseline electrocardiogram showed sinus rhythm and right bundle branch block, with no evidence of preexcitation. Electrophysiology study showed an atrial-His (AH) interval of 73 ms, a His-ventricular interval of 48 ms, and an RR interval of 876 ms.

An atypical long RP tachycardia—What is the mechanism?

Case presentation A 44-year-old man with recurrent palpitations and electrocardiogram-documented long RP interval supraventricular tachycardia despite metoprolol therapy underwent diagnostic electrophysiologic evaluation. His resting 12-lead electrocardiogram was normal. During sinus rhythm, atrio-His (AH) and His-ventricular intervals measured 51 and 39 ms, respectively. Antegrade dual atrioventricular (AV) nodal physiology was not observed. In the baseline state, tachycardia could not be induced but on isoproterenol, the patient

An unusual wide QRS complex tachycardia: What is the mechanism?

Case presentation A 15-year-old boy was referred to our institution because of a single episode of rapid nonsyncopal palpitations in the absence of structural heart disease. A regular wide QRS complex tachycardia (210 beats/min, left-bundle-branchblock morphology) (Figure 1A) that was terminated by a bolus of intravenous adenosine in his hospital of origin was documented. An electrophysiological study was subsequently performed. A traumatic right bundle branch block developed during catheter positioning and was present throughout the entire procedure. The baseline sinus cycle length and atrial-His (AH) and His-ventricular intervals were 810, 95, and 45 ms, respectively. Dual atrioventricular (AV) node physiology and a single AV nodal echo beat were demonstrated. Ventricular pacing during sinus rhythm showed ventriculoatrial conduction that was concentric and decremental. During isoproterenol infusion, a sustained tachycardia (Figure 1B) with QRS and cycle length alternans was reproducibly induced by programmed atrial stimulation. Induction of the tachycardia by atrial extrastimulus testing and the response to a single premature atrial extrastimulus introduced during His refractoriness were repeatedly observed (Figure 2). Overdrive ventricular pacing during tachycardia at a pacing cycle length of 10–20 ms below the atrial rate failed to affect the atria. What is the mechanism of the tachycardia? What is the cause of QRS and cycle length alternans?

A long RP-interval tachycardia: What is the mechanism?

c p I H d f “ l d c “ Case presentation A 31-year-old man with a long history of palpitations underwent diagnostic electrophysiologic study. Baseline 12lead electrocardiogram and echocardiography were normal. Atrio-His and His-ventricular intervals measured 83 and 44 ms, respectively. Dual atrioventricular (AV) node physiology was observed during programmed atrial extrastimulation. Spontaneous ventricular premature depolarizations repeatedly induced a long RP-interval supraventricular tachycardia that consistently terminated during attempts to entrain it from the ventricle (Figure 1, top). Retrograde ventriculoatrial (VA) conduction was midline and identical to that during tachycardia, with the response to para-Hisian pacing at a cycle length of 700 ms shown in Figure 1 (bottom). Figures 2 and 3 show reinduction of tachycardia after its termination during attempted entrainment and development of transient right bundle branch block during tachycardia, respectively. Based on these findings, what is the mechanism of tachycardia?

Prophylactic pacemaker implantation in familial amyloid polyneuropathy

Familial amyloid polyneuropathy (FAP) is an autosomic dominant disease with a high rate of conduction disorders and increased risk of sudden death. Prophylactic cardiac pacing may be considered in asymptomatic patients with FAP. However, the potential benefits are unknown. To document conduction disorders in a large series of FAP and the incidence of high-degree atrioventricular (AV) block in patients with prophylactic pacemaker (PM). From January 1999 to January 2010, 262 patients with FAP were retrospectively evaluated. Prophylactic PM was implanted in patients with His-ventricular interval ≥ 70 ms, His-ventricular interval >55 ms associated with a fascicular block, a first-degree AV block, or a Wenckebach anterograde point ≤ 100 beats/min. The spontaneous AV conduction was then analyzed by temporarily inhibiting the PM. As compared with patients with prophylactic PM (n = 100) and patients implanted given a class I/IIa indication (n = 18), the patients who did not require PM (n = 144) were younger and displayed less severe cardiac involvement. Follow-up after prophylactic PM implantation was analyzed in 95 of the 100 patients over 45 ± 35 months, and a high-degree AV block was documented in 24 of the 95 patients (25%). The risk of high-degree AV block was higher in patients with first-degree AV block or Wenckebach anterograde point ≤ 100 beats/min (hazard ratio 3.5; 95% confidence interval 1.2-10) while microvoltage on surface electrocardiogram reduced the risk (hazard ratio 0.2; 95% confidence interval 0.1-0.7). In FAP with conduction disorders, prophylactic PM implantation prevented major cardiac events in 25% of the patients over a 45-month mean follow-up. It is suggested that prophylactic PM implantation prevented symptomatic bradycardia in these patients.

Abstract 9290: Clinical, Electrocardiographic, and Genetic Characteristics of Patients with Idiopathic Ventricular Fibrillation Associated with Early Repolarization

Background: Early repolarization or J-wave has generally been considered benign for decades. However, we and others recently reported that early repolarization is associated with idiopathic ventricular fibrillation (VF). This study aimed to investigate its clinical and genetic characteristics and to identify risk factors for arrhythmia events. Methods and results: This study included 38 patients (32 men; age, 42±17 years) with idiopathic VF associated with early repolarization. All of the patients had arrhythmia events. The events occurred during sleeping (n=12) or at rest (n=9) in more than half of the patients. An electrical storm defined as ≥3 episodes of VF during 24 hours was observed in 8 patients (21%). A family history of sudden cardiac death was reported in 7 patients (18%). In 12-lead electrocardiograms, early repolarization was present in the inferior leads in 9 patients, in the lateral/precordial leads in 12 patients, and in both of the inferior and lateral/precordial leads in the remaining 17 patients. Conduction disease, mostly prolongation of PR interval, was present in 13 patients (34%). The heart rate was slower, and the PR interval and QRS duration were longer in patients with idiopathic VF compared to 190 age- and sex-matched healthy controls. VF was inducible by programmed electrical stimulation in 15 of 27 patients (55%). We identified loss-of-function mutations in SCN5A in 3 unrelated patients, and interestingly, His-ventricular interval was prolonged in all of them. During a follow-up of 6.0±5.7 years, VF recurred in 9 patients. Multivariate analyses revealed that a family history of sudden cardiac death and a history of electrical storm were associated with increased risk of arrhythmia recurrences. The age of arrhythmia onset, gender, lead location of early repolarization, activity at the initial event, conduction disease, or inducibility of VF were not associated with the risk of recurrences. Conclusions: This study showed the clinical and genetic characteristics of idiopathic VF associated with early repolarization, suggesting the underlying mechanism for arrhythmia susceptibility. Our data may be useful for risk stratification for arrhythmia events.

Electrocardiographic Characteristics and SCN5A Mutations in Idiopathic Ventricular Fibrillation Associated With Early Repolarization

Recently, we and others reported that early repolarization (J wave) is associated with idiopathic ventricular fibrillation. However, its clinical and genetic characteristics are unclear. This study included 50 patients (44 men; age, 45 ± 17 years) with idiopathic ventricular fibrillation associated with early repolarization, and 250 age- and sex-matched healthy controls. All of the patients had experienced arrhythmia events, and 8 (16%) had a family history of sudden death. Ventricular fibrillation was inducible by programmed electric stimulation in 15 of 29 patients (52%). The heart rate was slower and the PR interval and QRS duration were longer in patients with idiopathic ventricular fibrillation than in controls. We identified nonsynonymous variants in SCN5A (resulting in A226D, L846R, and R367H) in 3 unrelated patients. These variants occur at residues that are highly conserved across mammals. His-ventricular interval was prolonged in all of the patients carrying an SCN5A mutation. Sodium channel blocker challenge resulted in an augmentation of early repolarization or development of ventricular fibrillation in all of 3 patients, but none was diagnosed with Brugada syndrome. In heterologous expression studies, all of the mutant channels failed to generate any currents. Immunostaining revealed a trafficking defect in A226D channels and normal trafficking in R367H and L846R channels. We found reductions in heart rate and cardiac conduction and loss-of-function mutations in SCN5A in patients with idiopathic ventricular fibrillation associated with early repolarization. These findings support the hypothesis that decreased sodium current enhances ventricular fibrillation susceptibility.

An unusual long RP tachycardia: What is the mechanism?

A 43-year-old woman with frequent palpitations since childhood underwent diagnostic electrophysiologic evaluation. She had failed treatment with both metoprolol and flecainide. Transthoracic echocardiography was normal, and her 12-lead electrocardiogram showed no ventricular preexcitation. At baseline, atrio-His (AH) and His-ventricular intervals measured 103 and 54 ms, respectively, dual atrioventricular (AV) node physiology was not observed, ventriculoatrial (VA) conduction was intermittent at a pacing cycle length (PCL) of 600 ms, and nonsustained runs of tachycardia occurred spontaneously and became incessant on administration of isoproterenol (0.5 G/min) (Figure 1, upper panel). Tachycardia terminated fter administration of 3 mg of adenosine (Figure 1, ower panel). Figure 2 shows a ventricular premature epolarization (VPD) delivered during tachycardia when he His bundle is refractory (upper panel) and an attempt t entrainment of tachycardia from the ventricle (lower anel). Figure 3 shows successful entrainment of tachyardia from both the ventricle (upper panel) and the trium (lower panel) at a cycle length 10 ms shorter than tachycardia. Based upon these findings, what is the mechanism of tachycardia?

His Bundle Extrasystoles Revisited: The Great Electrocardiographic Masquerader

A 74-year-old man with past history of near syncope presented with frequent periods of second-degree atrioventricular block (2° AVB). An electrophysiological study revealed prolonged atrial-His and His-ventricular (HV) intervals and frequent His bundle (H) extrasystoles. The latter manifested in the surface electrocardiogram as premature atrial, junctional, or ventricular beats, as well as 2° AVB that mimicked Wenckebach or Mobitz II block. Procainamide markedly suppressed H extrasystole. However, because of the presence of prolonged HV interval and history of presyncope, a permanent pacemaker was inserted. The case illustrates the varied manifestation of H extrasystole and presents guidelines for management.

The Cardiac Conduction System

The human heart beats 2.5 billion times during a normal lifespan, a feat accomplished by cells of the cardiac conduction system (CCS). The functional components of the CCS can be broadly divided into the impulse-generating nodes and the impulse-propagating His-Purkinje system. Human diseases of the conduction system have been identified that alter impulse generation, impulse propagation, or both. CCS dysfunction is primarily due to acquired conditions such as myocardial ischemia/infarct, age-related degeneration, procedural complications, and drug toxicity. Inherited forms of CCS disease are rare, but each new mutation provides invaluable insight into the molecular mechanisms governing CCS development and function. Applying a multidisciplinary approach, which includes human genetic screening, biophysical analysis, and transgenic mouse technology, has yielded a broad array of gene families involved in maintaining normal CCS physiology (Figure 1). In this review, we discuss gene families that have been implicated in human CCS diseases of rhythm, conduction block, accessory conduction, and development (Table). We also investigate evolving therapeutic strategies that may serve as adjuvant or replacement therapy to current implantable pacemakers. Figure 1. Cardiac conduction system cell. Genes identified in human cardiac conduction system disease are highlighted. View this table: Table. Genetic Basis of Conduction System Disease The human sinoatrial node (SAN) is a crescent-shaped, intramural structure with its head located subepicardially at the junction of the right atrium and the superior vena cava and its tail extending 10 to 20 mm along the crista terminalis.26 The SAN has complex 3-dimensional tissue architecture with central and peripheral components made up of distinct ion channel and gap junction expression profiles.27 Central and peripheral cells have different action potential characteristics and conduction properties (Figure 2).27 Experimental and computational models have demonstrated that SAN heterogeneity is necessary to maintain normal automaticity and impulse conduction.28,–,30 Figure 2. Electrophysiological heterogeneity of the …