Hybrid therapy for ventricular arrhythmia management.

Optimum arrhythmia management has evolved to couple ICD therapy with catheter ablative and drug therapy to attempt to eliminate or reduce arrhythmia risk. No longer should the clinician approach such therapy as a choice among single alternative strategies only. Optimum patient management includes not only recognition of the indications and benefits of such hybrid therapy but also a complete understanding of potential pitfalls of such therapy.

Localization of arrhythmogenic triggers of atrial fibrillation.

INTRODUCTION: Mapping procedures to identify triggers of atrial fibrillation from pulmonary veins (PVs) are not well established. We sought to determine the value of multipolar recordings from the coronary sinus (CS) and crista terminalis (CT) for identifying the origin of paced and atrial premature depolarizations (APDs) initiating atrial fibrillation from left versus right PVs. METHODS AND RESULTS: Fifteen patients with paroxysmal atrial fibrillation refractory to medications had decapolar catheters (5-mm electrode, 2-mm interelectrode spacing) placed in the CS and posterior medial to the CT. Bipolar electrograms were recorded at each site. Electroanatomic left atrial endocardial maps were created in sinus rhythm, and each PV was identified and paced. During spontaneous APDs initiating atrial fibrillation and PV pace maps, the atrial activation and the earliest electrogram at CS and CT were compared. PV sites were designated as sites of origin of APDs when (1) intracardiac electrograms in the CS and CT during arrhythmogenic APDs matched those of PV pace maps, (2) local activation preceded CS and CT recordings by at least 40 msec (all sites), and (3) atrial depolarizations were eliminated by application of radiofrequency energy (24/26 sites). Pacing from each of the 30 right PV sites resulted in proximal to distal CS activation and later recordings at the CS than the CT (earliest CS-CT activation range: -15 to -58 msec, mean -32 +/- 12). In contrast, pacing from the left PV sites typically (28/30 sites) activated the CS from the distal to proximal poles and demonstrated simultaneous or earlier (CS-CT range: -14 to +54 msec, mean 13 +/- 17) recordings of the CS than the CT (P < 0.0001). For 13 APDs mapped to the right PVs, CS minus CT activation was -17 to -49 msec (mean -31 +/- 8). For 13 APDs localized to the left PVs, the CS minus CT activation time ranged from -8 to +28 msec (mean 14 +/- 15). CONCLUSION: Activation sequence mapping from multipolar catheters placed in the CS and along the posterior medial CT rapidly differentiates right and left PV sites of origin of atrial depolarization.

Relationship between heart rate and oxygen kinetics during constant workload exercise.

BACKGROUND: Oxygen uptake during constant workload exercise increases exponentially from its resting value before reaching a steady state. The difference between the actual rate of oxygen consumption at the onset of exercise and the steady state is an oxygen deficit. Similarly, the normal sinus node increases its rate at the onset of exercise before achieving a steady state, thereby producing a heart rate deficit. The purpose of this study was to test the hypothesis that elimination of the heart rate deficit by an instantaneous increase in heart rate at the onset of constant workload exercise to the steady-state level would reduce the oxygen deficit and improve the perceived difficulty of exertion as compared with the chronotropic response of the normal sinus node. METHODS AND RESULTS: Ten subjects with normal sinus node function who had DDD pacemakers implanted for AV block completed a symptom-limited maximal treadmill exercise test using the Chronotropic Assessment Exercise Protocol (CAEP) to assess sinus node function, maximal heart rate, and VO2max. The subjects then performed constant workload exercise tests (6-min duration) at a workload equal to approximately 50% of metabolic reserve with the pacemaker randomly programmed to each of three patterns of chronotropic response: (1) DDD (lower rate 60 beats/min); (2) Fast (lower rate abruptly programmed to the expected value at 50% metabolic reserve); and (3) Overpaced (lower rate at least 80% of the age predicted maximum). The oxygen deficit was lower with the fast chronotropic response (434 +/- 238 mL O2) than with either the DDD (512 +/- 233; P = 0.02), or overpaced chronotropic patterns (488 +/- 238; P = 0.02 vs fast). The rate constant for change in VO2 was highest with the fast chronotropic pattern (2.85 +/- 1.38) compared with either the DDD (2.25 +/- 0.64; P = 0.01) or overpaced (2.38 +/- 0.43; P = 0.02) patterns. The Borg perceived exertion rating was lowest with the fast chronotropic response (P = 0.02 vs DDD and P = 0.02 vs overpaced). CONCLUSIONS: The results of this study suggest that oxygen kinetics and exertional symptoms are improved by an abrupt increase in pacing rate at the onset of exercise to a value that is appropriate for metabolic demand as compared with the DDD pacing mode in patients with normal sinus node function. In contrast, an overly aggressive chronotropic response was not associated with improved oxygen kinetics or exertional symptoms.

Receptor-mediated cardioprotective effects of endogenous adenosine are exerted primarily during reperfusion after coronary occlusion in the rabbit.

BACKGROUND: We hypothesized that: (1) endogenous adenosine released during ischemia/reperfusion reduces infarct size and preserves postischemic myocardial blood flow by receptor-mediated mechanisms and (2) this cardioprotection is exerted predominantly during reperfusion. METHODS AND RESULTS: Sixty-one anesthetized open-chest rabbits subjected to 30 minutes of coronary occlusion and 120 minutes of reperfusion were randomized to six groups: group 1, saline (Vehicle) (n = 10) to allow receptor interaction of endogenous adenosine (Ado) during ischemia/reperfusion; group 2, Ado-receptor blockade during both ischemia and reperfusion with intravenous 8-p-sulfophenyltheophyl-line (10 mg/kg) (SPTIR, n = 10); group 3, Ado-receptor blockade in multiple doses during both ischemia and reperfusion (MSPTIR, n = 11); group 4, blockade during reperfusion (SPTR, n = 10); group 5, blockade during reperfusion with PD115,199 (6 mg/kg) (PDR, n = 10); and group 6, blockade after 30 minutes of reperfusion (SPT30R, n = 10) to allow adenosine receptor interaction during early reperfusion. Transmural myocardial blood flow in the area at risk (Ar) (15-microns radiolabeled microspheres) was reduced by 96.7% in all groups, from 137.9 +/- 15.5 to 4.5 +/- 1.4 mL.min-1 x 100 g-1 (P < .001). MSPTIR, SPTIR, and SPTR significantly attenuated reactive hyperemia at 15 minutes of reperfusion (144 +/- 18, 141 +/- 22, and 144 +/- 20 mL.min-1 x 100 g-1, respectively) compared with Vehicle (257 +/- 40 mL.min-1 x 100 g-1, P < .05). This attenuation was more pronounced in the necrotic zone than in the nonnecrotic zone. Reactive hyperemia at 15 minutes of reperfusion in SPT30R group was comparable to the Vehicle group. At 120 minutes of reperfusion, blood flow in Ar was significantly less in MSPTIR (77 +/- 10), SPTIR (82 +/- 9), and SPTR (80 +/- 11) compared with Vehicle (140 +/- 12) and SPT30R (105 +/- 24 mL.min-1 x 100 g-1). Infarct size (by triphenyltetrazolium chloride), expressed as a percent of Ar, was largest in the multiple-dose group with blockade during both ischemia and reperfusion (MSPTIR, 51.9 +/- 2.3%) and was significantly increased also in single-dose SPTIR (39.1 +/- 2.2%) compared with 25.7 +/- 1.7% in the Vehicle group (P < .05). Ado-receptor blockade only during reperfusion was associated with 14% smaller infarct size in the SPTR group than the MSPTIR group (P < .05). In contrast, Ado-receptor blockade after 30 minutes of reperfusion (SPT30R) did not increase infarct size (27.9 +/- 2.2%), which was comparable to infarct size in the Vehicle group. CONCLUSIONS: We conclude that: (1) endogenous adenosine released from the myocardium during ischemia/reperfusion reduces infarct size by receptor-mediated mechanisms and (2) Ado-mediated cardioprotection is most pronounced during the early phase of reperfusion.