The impact of circulating cholesterol crystals on vasomotor function: implications for no-reflow phenomenon.

OBJECTIVES: The purpose of this study was to determine if cholesterol crystals can injure the endothelial surface by their jagged edges altering vasoreactivity and contributing to no-reflow after intervention. BACKGROUND: After plaque rupture, cholesterol crystals are released into the circulation and flow downstream contacting the arterial wall. METHODS: Both carotid arteries from 22 rabbits were placed in a dual perfusion chamber and challenged with norepinephrine followed by acetylcholine and nitroprusside. Arterial diameters were measured before and after exposure to cholesterol crystals or microspheres and compared with diameters of normal control arteries. Arteries were examined by light, confocal, atomic force and scanning electron microscopy. RESULTS: Pre-exposure mean arterial diameter was 2.33 ± 0.27 mm. With baseline norepinephrine there was vasoconstriction of 0.82 ± 0.19 mm, 0.79 ± 0.18 mm, and 0.83 ± 0.16 mm in lumen diameter in the crystal, microsphere, and control groups, respectively. After cholesterol crystals or microspheres, vasoconstriction was significantly less for cholesterol crystals but not for microspheres (0.71 ± 0.28 mm and 0.81 ± 0.15 mm; p < 0.02 and p = 0.68). After acetylcholine in the same artery, there was significantly less dilation before versus after crystals (0.49 ± 0.24 mm vs. 0.38 ± 0.22 mm, p = 0.04) but not with microspheres or in the control group. There was no significant difference after nitroprusside in any group, suggesting endothelial injury. By scanning electron microscopy, cholesterol crystals were found embedded in the intima with endothelial cell tears whereas the microsphere treatment and control groups had minimal or no injury (93% vs. 31% vs. 14%; p < 0.01). By atomic force microscopy, surface roughness was significantly greater with cholesterol crystals compared with microspheres or in control arteries (p < 0.05). CONCLUSIONS: Cholesterol crystals damaged the endothelium and reduced vasodilator response, potentially aggravating myocardial ischemia after interventions.

Inappropriate Implantable Cardioverter-Defibrillator Therapy.

Although improvements in implantable cardioverter-defibrillator (ICD) therapy have taken place, many challenges do remain. Inappropriate delivery of therapy is a big problem that impacts the quality of life of ICD recipients. Although there is now a clear understanding that atrial arrhythmias are the main cause of inappropriate ICD therapies, physicians have not been very successful in preventing them. Additionally, although many tachycardia detection discriminators have been shown to be helpful, it is not clear that there is a particular combination that is ideal for all patients. Until such an algorithm is developed (which may not be possible), a detailed knowledge and use of all available programming options, guided by special characteristics of each unique patient, are the only foreseeable solutions. Finally, one must face the prospect that this problem cannot be vanquished, but only ameliorated.

Inducibility of paroxysmal atrial fibrillation by isoproterenol and its relation to the mode of onset of atrial fibrillation.

BACKGROUND: Isoproterenol has been used to assess inducibility during catheter ablation for paroxysmal PAF. However, no studies have determined the sensitivity and specificity of isoproterenol for the induction of AF. It also is not clear whether isoproterenol is equally effective in inducing AF in the clinical subtypes of vagotonic, adrenergic, and random AF. OBJECTIVE: To determine the sensitivity and specificity of isoproterenol for the induction of atrial fibrillation (AF). METHODS: Isoproterenol was infused at 5, 10, 15, and 20 microg/min at 2-minute intervals or until AF was induced in 20 control subjects with no history of AF and in 80 patients with PAF. RESULTS: Among the 20 control subjects, AF was induced by isoproterenol in one patient (5%). Among the 80 patients with PAF, persistent AF was induced in 67 patients (84%, P < 0.001). Isoproterenol induced AF in 15 of 17 patients (88%) with vagotonic AF, 11 of 11 patients (100%) with adrenergic AF, and 41 of 52 patients (79%) with random episodes of AF (P = 0.2). The yield of AF was 11% (9/80) after 5 microg/min, 28% (22/80) after 10 microg/min, 51% (40/78) after 15 microg/min, and 88% (67/76) after 20 microg/min of isoproterenol (P < 0.01). Isoproterenol had to be discontinued in four patients (5%) before reaching the maximum dose due to reversible chest pain or systolic blood pressure <85 mmHg. CONCLUSIONS: Isoproterenol at infusion rates up to 20 microg/min has a high sensitivity (88%) and specificity (95%) for induction of AF in patients with PAF, regardless of whether the clinical subtype is vagotonic, adrenergic, or random.

Randomized evaluation of right atrial ablation after left atrial ablation of complex fractionated atrial electrograms for long-lasting persistent atrial fibrillation.

BACKGROUND: With electrogram-guided radiofrequency ablation (RFA) of long-lasting persistent atrial fibrillation (AF), the best results have been reported when complex fractionated electrograms (CFAEs) in both the left (LA) and right (RA) atria were targeted. However, many studies have reported excellent outcomes from RFA of long-lasting persistent AF with the use of other ablation strategies that were limited to the LA. The incremental value of RFA of RA CFAEs is yet to be defined. METHODS AND RESULTS: In 85 patients with long-lasting persistent AF (age=59+/-10 years), RFA was directed at CFAEs in the LA and coronary sinus until AF terminated (19) or all identified LA CFAEs were eliminated. Sixty-six patients who remained in AF were randomly assigned to cardioversion and no further RFA (n=33) or to RFA of RA CFAEs (n=33). RA sites consisted of the crista terminalis (69%), septum (38%), superior vena cava (28%), coronary sinus ostium (22%), and the base of the appendage (31%). AF terminated in 1 (3%) of 33 patients during RA RFA. At 17+/-6 months after a single ablation procedure, 74% of the patients in whom AF terminated during LA RFA were in sinus rhythm. Rates of freedom from AF were similar in the patients randomized to no RFA in the RA (24%) and those randomized to RFA of RA CFAEs (30%, P=0.8). The ablation procedure was repeated in 26 patients (31%) for AF (n=22) or atrial flutter (n=4). At 16+/-7 months after the final procedure, 89% of the patients in whom AF terminated during LA RFA were in sinus rhythm. Among the randomized patients, the proportion of patients who remained in sinus rhythm was similar in patients who did not undergo RFA of RA CFAEs (52%) and those who did (58%, P=0.6). CONCLUSIONS: After RFA of CFAEs in the LA and coronary sinus, ablation of CFAEs in the RA provides little or no increment in efficacy among patients with long-lasting persistent AF.

Radiofrequency catheter ablation of chronic atrial fibrillation guided by complex electrograms.

BACKGROUND: Radiofrequency catheter ablation of atrial fibrillation (AF) guided by complex fractionated atrial electrograms has been reported to eliminate AF in a large proportion of patients. However, only a small number of patients with chronic AF have been included in previous studies. METHODS AND RESULTS: In 100 patients (mean age, 57+/-11 years) with chronic AF, radiofrequency ablation was performed to target complex fractionated atrial electrograms at the pulmonary vein ostial and antral areas, various regions of the left atrium, and the coronary sinus until AF terminated or all identified complex fractionated atrial electrograms were eliminated. Ablation sites consisted of > or = 1 pulmonary vein in 46% of patients; the left atrial septum, roof, or anterior wall in all; and the coronary sinus in 55%. During 14+/-7 months of follow-up after a single ablation procedure, 33% of patients were in sinus rhythm without antiarrhythmic drugs, 38% had AF, 17% had both AF and atrial flutter, 9% had persistent atrial flutter, and 3% had paroxysmal AF on antiarrhythmic drugs. A second ablation procedure was performed in 44% of patients. Pulmonary vein tachycardia was found in all patients in both previously targeted and nontargeted pulmonary veins. There were multiple macroreentrant circuits in the majority of patients with atrial flutter. At 13+/-7 months after the last ablation procedure, 57% of patients were in sinus rhythm without antiarrhythmic drugs, 32% had persistent AF, 6% had paroxysmal AF, and 5% had atrial flutter. CONCLUSIONS: Modest short-term efficacy is achievable with radiofrequency ablation of chronic AF guided by complex fractionated atrial electrograms, but only after a second ablation procedure in > 40% of patients. Rapid activity in the pulmonary veins and multiple macroreentrant circuits are common mechanisms of recurrent atrial arrhythmias.