Edmund C. Keung

Calcium current is increased in isolated adult myocytes from hypertrophied rat myocardium.

To study the effects of myocardial hypertrophy resulting from chronic pressure overload on excitation-contraction coupling, the cardiac transmembrane L-type calcium current (ICa) was investigated in the Goldblatt renovascular hypertensive (HBP) rat. ICa was measured in single myocytes enzymatically isolated from control (CTRL) and HBP rat hearts using the whole-cell, patch-clamp method. The peak ICa and ICa density (obtained by normalizing ICa to the average cell capacitative surface area) were larger in HBP cells (n = 15) than in CTRL cells (n = 10) at membrane potentials of -20 to 50 mV (p less than 0.01). The maximal peak ICa increased from 0.9 +/- 0.5 nA (mean +/- SD) in CTRL cells to 2.8 +/- 1.0 nA in HBP cells (p less than 0.001). The corresponding ICa density increased from 5.3 +/- 2.7 to 16.2 +/- 6.0 microA/cm2 (p less than 0.001). There was no shift in the current-voltage relation between CTRL and HBP cells. The time course of decay of HBP ICa in response to clamp steps to the plateau range of the action potential (membrane potential, Vm = -10 to 30 mV) was delayed when compared with that of CTRL ICa. The inactivation time constants (biexponential) for the maximal ICa were 6.9 +/- 1.9 and 36.0 +/- 9.3 msec for CTRL cells and 6.7 +/- 1.4 and 49.5 +/- 12.9 msec for HBP cells (p less than 0.05 for the slower component of the maximal ICa). There was no difference in the steady-state inactivation of ICa (f infinity) for the CTRL and HBP cells. From the maximal peak ICa, cytoplasmic free Ca2+ was estimated to reach a pCa of 6.95 +/- 0.07 for CTRL cells and 6.64 +/- 0.13 for HBP cells. It is concluded that ICa is increased with myocardial hypertrophy. The lengthening of the action potential in hypertrophied rat myocardium is due to an increase in peak current density and to the slower inactivation of the maximal ICa. The increased transmembrane flux of Ca2+ via ICa in HBP cells is inadequate to achieve a myoplasmic free Ca2+ level sufficient for direct partial activation of the contractile myofilaments. However, in the scheme of the calcium-triggered calcium release hypothesis such an increase could provide an increased amount of activator calcium and/or serve to amplify the release of Ca2+ from sarcoplasmic reticulum, thereby contributing to preserved peak developed tension in hypertrophied rat myocardium.

Dual-chamber implantable cardioverter-defibrillator selection is associated with increased complication rates and mortality among patients enrolled in the NCDR implantable cardioverter-defibrillator registry.

OBJECTIVES The aim of this study was to compare single- versus dual-chamber implantable cardioverter-defibrillator (ICD) implantation and complication rates in a large, real-world population. BACKGROUND The majority of patients enrolled in ICD efficacy trials received single-chamber devices. Although dual-chamber ICDs offer theoretical advantages over single-chamber defibrillators, the clinical superiority of dual-chamber models has not been conclusively proven, and they may increase complications. METHODS The National Cardiovascular Data Registry ICD Registry was used to examine the association between baseline characteristics and device selection in 104,049 patients receiving single- and dual-chamber ICDs between January 1, 2006, and December 31, 2007. A longitudinal cohort design was then used to determine in-hospital complication rates. RESULTS Dual-chamber devices were implanted in 64,489 patients (62%). Adverse events were more frequent with dual-chamber than with single-chamber device implantation (3.17% vs. 2.11%, p < 0.001), as was the rate of in-hospital mortality (0.40% vs. 0.23%, p < 0.001). After adjusting for demographics, medical comorbidities, diagnostic test data, and ICD indication, the odds of any complication (odds ratio: 1.40; 95% confidence interval: 1.28 to 1.52; p < 0.001) and in-hospital mortality (odds ratio: 1.45; 95% confidence interval: 1.20 to 1.74; p < 0.001) were increased with dual-chamber versus single-chamber ICD implantation. CONCLUSIONS In this large, multicenter cohort of patients, dual-chamber ICD use was common. Dual-chamber device implantation was associated with increases in periprocedural complications and in-hospital mortality compared with single-chamber defibrillator selection.

Surface Electrocardiographic Characteristics of Right and Left Atrial Flutter

Background There is little information about the surface expression of non‐cavotricuspid isthmus (CTI)‐ dependent right atrial (RA) or left atrial (LA) flutter circuits. Methods and Results We retrospectively evaluated 32 episodes (in 26 patients) of atypical RA and 22 episodes (in 21 patients) of LA flutter. The surface ECG of 13 patients with lower‐loop reentry was similar to that of their pattern during counterclockwise (CCW) CTI atrial flutter (AFL), except for decreased amplitude of the terminal forces in the inferior leads. In 11 of 24 episodes characterized by high or multiple breaks over the crista, the ECG showed changes that depended on the initial activation sequence of the LA. In 7 of 8 episodes of upper‐loop reentry, the ECG pattern completely mimicked that for clockwise (CW) CTI AFL. All 11 patients with an LA septal circuit showed a typical ECG pattern characterized by prominent forces in lead V1 with flat deflections in the other surface leads. Eleven patients with other LA circuits had a more variable pattern but showed decreased voltage in the inferior leads compared with that of a group with CCW‐CTI AFL (1.6±1 vs 2.68±0.7 mV, respectively; P<0.05). Conclusions The RA surface‐ECG patterns different from those of CCW or CW‐CTI could still be CTI dependent. In contrast, a typical CW‐CTI surface pattern was always seen in patients with upper‐loop reentry, which was non‐CTI dependent. LA AFL circuits had either flat or low‐amplitude forces in the inferior leads. (Circulation. 2003;108:60‐66.)

Long-term electrical survival analysis of Riata and Riata ST silicone leads: National Veterans Affairs experience

BACKGROUND A medical device advisory issued by St Jude Medical in November 2011 estimated 0.63% all-cause abrasion rate on their Riata and Riata ST silicone high-voltage lead families (Riata/ST), leading to Food and Drug Administration class I recall. We performed an independent comparative, long-term electrical survival analysis of Riata/ST and 3 other high-voltage lead families in a large national cohort of patients. OBJECTIVE To evaluate long-term electrical survival of Riata/ST leads relative to other commonly evaluated high-voltage leads. METHODS Failure rates of Riata/ST, Sprint Quattro Secure (Quattro), Sprint Fidelis (Fidelis), and Endotak Reliance G/SG (Endotak) leads from the Veterans Administrations National Cardiac Device Surveillance Center database, consisting of 24,145 patients with remote transmissions since 2003, were analyzed. Survival Probabilities were determined with Kaplan-Meier survival analysis and compared using the log-rank test. RESULTS Of 1,403 Riata/ST, 6,091 Quattro, 5,073 Fidelis, and 2,401 Endotak leads identified, 5-year survival probability of Riata/ST leads (97.5%) was significantly lower than that of Quattro (99.3%) and Endotak (99.4%) leads (P <.0001) but higher than that of Fidelis leads (89.6%) (P <.0001). Riata ST leads showed a 5-year survival of 95.5% (95% confidence interval 92.4-97.4) compared to 98.4% (95% confidence interval 97.1-99.1) in Riata leads (P = .003). CONCLUSIONS There is decreased survival probability of Riata/ST leads compared to other contemporary high-voltage leads, with decreased survival of Riata ST silicone compared to Riata lead series. Careful long-term follow-up should be maintained in patients with Riata/ST leads in order to prevent inappropriate shocks or failed device interventions. Our results were determined in advance of Food and Drug Administration class I recall, which suggested that large-scale remote monitoring may be an effective tool for continued implantable cardioverter-defibrillator system surveillance.

Role of intravenous isoproterenol in the electrophysiologic induction of atrioventricular node reentrant tachycardia in patients with dual atrioventricular node pathways.

To assess the role of intravenous isoproterenol for the facilitation of electrophysiologic induction of atrioventricular (AV) node reentrant tachycardia, 20 patients with dual AV node pathways who lacked inducible AV node reentrant tachycardia at control study had a constant isoproterenol infusion administered and underwent repeat study. Six (30%) of 20 patients (group I) had inducible AV node reentrant tachycardia during isoproterenol infusion whereas the other 14 (70%) patients (group II) did not. Paroxysmal supraventricular tachycardia was clinically documented in all 6 group I patients compared to 3 (21%) of 14 group II patients (p = 0.002). The sensitivity and specificity of isoproterenol-facilitated induction of AV node reentrant tachycardia were 67 and 100%, respectively. The isoproterenol-facilitated induction of sustained AV node reentry was mediated by resolution of the weak link in anterograde slow pathway in 2 (33%) patients, in retrograde fast pathway in 3 (50%) and in both anterograde slow and retrograde fast pathways in 1 (17%) patient. Four group I patients were given intravenous propranolol, 0.2 mg/kg body weight, and had complete suppression of isoproterenol-facilitated induction of AV node reentry. Thus, intravenous isoproterenol is a rather sensitive and highly specific adjunct to electrophysiologic induction of AV node reentrant tachycardia in patients with dual AV node pathways but without inducible sustained AV node reentry.

Intravenous Propafenone for Termination of Reentrant Supraventricular Tachycardia: A Placebo-Controlled, Randomized, Double-Blind, Crossover Study

To assess the antiarrhythmic efficacy of intravenous propafenone, 20 patients with inducible sustained supraventricular tachycardia received propafenone, 2 mg/kg body weight, or placebo in a double-blind, randomized, crossover study. Three patients had intra-atrial reentrant tachycardia, 3 had atrioventricular nodal reentrant tachycardia, and 14 had atrioventricular reciprocating tachycardia associated with the Wolff-Parkinson-White syndrome. Termination of supraventricular tachycardia occurred in 15 of the 20 patients receiving propafenone but 0 of the 11 patients receiving placebo (p less than 0.01). Propafenone prolonged refractoriness and slowed conduction of the atrium, the atrioventricular node, and accessory atrioventricular bypass tracts, and these effects provided antiarrhythmic action to halt tachycardia. No adverse effects were observed in any patient. We conclude that intravenous propafenone is safe and effective in the acute treatment of various forms of reentrant supraventricular tachycardia.

Reentry Within the Cavotricuspid Isthmus: An Isthmus Dependent Circuit

Background: We describe a new cavotricuspid isthmus (CTI) circuit.

Ca2+ regulates the kinetics of tension development in intact cardiac muscle

The goal of this study was to determine whether Ca2+ plays a role in regulating tension development kinetics in intact cardiac muscle. In cardiac muscle, this fundamental issue of Ca2+ regulation has been controversial. The approach was to induce steady-state tetanic contractions of intact right ventricular trabeculae from rat hearts at varying external Ca2+concentrations ([Ca2+]) at 22°C. During tetani, cross bridges were mechanically disrupted and the kinetics of tension redevelopment were assessed from the rate constant of exponential tension redevelopment ( k tr). There was a relationship between k tr and external [Ca2+] that was similar in form to the relationship between tension and [Ca2+]. Thus a close relationship also existed between k tr and tension ( r = 0.88; P < 0.001); whereas at maximal tetanic tension (saturating cytosolic [Ca2+]), k tr was 16.4 ± 2.2 s-1 (mean ± SE, n = 7), at zero tension (low cytosolic [Ca2+]), k tr extrapolated to 20% of maximum (3.3 ± 0.7 s-1). Qualitatively similar results were obtained using different mechanical protocols to disrupt cross bridges. These data demonstrate that tension redevelopment kinetics in intact cardiac muscle are influenced by the level of Ca2+ activation. These findings contrast with the findings of one previous study of intact cardiac muscle. Activation dependence of tension development kinetics may play an important role in determining the rate and extent of myocardial tension rise during the cardiac cycle in vivo.The goal of this study was to determine whether Ca2+ plays a role in regulating tension development kinetics in intact cardiac muscle. In cardiac muscle, this fundamental issue of Ca2+ regulation has been controversial. The approach was to induce steady-state tetanic contractions of intact right ventricular trabeculae from rat hearts at varying external Ca2+ concentrations ([Ca2+]) at 22 degreesC. During tetani, cross bridges were mechanically disrupted and the kinetics of tension redevelopment were assessed from the rate constant of exponential tension redevelopment (ktr). There was a relationship between ktr and external [Ca2+] that was similar in form to the relationship between tension and [Ca2+]. Thus a close relationship also existed between ktr and tension (r = 0.88; P < 0. 001); whereas at maximal tetanic tension (saturating cytosolic [Ca2+]), ktr was 16.4 +/- 2.2 s-1 (mean +/- SE, n = 7), at zero tension (low cytosolic [Ca2+]), ktr extrapolated to 20% of maximum (3.3 +/- 0.7 s-1). Qualitatively similar results were obtained using different mechanical protocols to disrupt cross bridges. These data demonstrate that tension redevelopment kinetics in intact cardiac muscle are influenced by the level of Ca2+ activation. These findings contrast with the findings of one previous study of intact cardiac muscle. Activation dependence of tension development kinetics may play an important role in determining the rate and extent of myocardial tension rise during the cardiac cycle in vivo.

Optimizing the Detection of Bidirectional Block Across the Flutter Isthmus for Patients With Typical Isthmus-Dependent Atrial Flutter

The purpose of this study was to show that multipolar electrographic recordings along the subeustachian isthmus (SI) can better differentiate slow conduction from complete isthmus block after atrial flutter ablation, leading to a lower incidence of recurrent atrial flutter (Afl). Despite the presence of various techniques to identify bidirectional conduction block (BDB) after isthmus ablation for typical Afl, several studies, including a report from a national registry, suggest that radiofrequency ablation is still associated with a 15% recurrence rate. Thus, techniques that can distinguish slow conduction from complete isthmus block have the potential for reducing long-term recurrences. We evaluated patients who underwent radiofrequency ablation for typical isthmus-dependent Afl. Patients were separated into 2 groups. Group A underwent assessment of BDB with conventional methods. In group B, BDB was assessed by placing a multipolar catheter along the floor of the SI, pacing adjacent to the line of radiofrequency application, and assessing electrographic activation on either side. One hundred thirty-one cases of Afl ablation were analyzed (86 in group A, 45 in group B). Over a mean follow-up period of 17 months, recurrence rates of Afl were 16.5% in group A and 4.3% in group B (p = 0.043). Thus, assessment of BDB by placement of a multipolar catheter across the SI after ablation of typical Afl is associated with a significant reduction in long-term recurrence of Afl.

Electrophysiologic demonstration of concealed conduction in anomalous atrioventricular bypass tracts

To demonstrate the occurrence of concealed conduction in anomalous atrioventricular (AV) bypass tracts, 11 patients were selected for study. Two had a right-sided and nine had a left-sided bypass tract. Electrode catheters were placed in the right atrium, coronary sinus, AV junction and right ventricle. After every eighth atrial or ventricular driving beat (A1 or V1) at a constant cycle length, two successive atrial or ventricular premature beats (A2 and A3 or V2 and V3) were delivered. The A1A2 or V1V2 interval was fixed at 30 ms greater than the effective refractory period of the atrium or right ventricle, but less than the effective refractory period of the bypass tract in the anterograde or retrograde direction. This allows A2 or V2 to capture the atrium or ventricle, but not conduct in the bypass tract. The A3 or V3 was delivered from late diastole with a progressively shorter A2A3 or V2V3 interval until atrial or ventricular refractoriness was encountered. In the anterograde direction, the presence of A2 prevented A3 conduction in the bypass tract despite A1A3 intervals being longer than the anterograde effective refractory period of the bypass tract in 8 of the 11 patients. In the retrograde direction, the presence of V2 prevented V3 conduction in the bypass tract despite V1V3 intervals being longer than the retrograde effective refractory period of the bypass tract in 3 of the 11 patients. Thus, using the technique of programmed electrical stimulation, concealed conduction in anomalous AV bypass tracts can be demonstrated in both anterograde and retrograde directions.