Acute Efficacy and Chronic Follow-Up of Patients with Non-Thoracotomy Third Generation Implantahle Defibrillators

Non-thoracotomy implantation of implantable cardioverter defibrillators (ICDs) has simplified the process of device inserfion, promising to decrease associated procedural coniplications while providing sudden death protection at least equal to epicardial systems. This study presents the acute and chronic results of 110 patients who underwent attempted non-thoracotomy ICD impiuntation wiih the Medtronic Transvene lead system and PCD model 7217 or 7219. Of the 110 patients attempted, 100 (91%) had the system successfully implanted without the need for an epicar-dial patch. One patient died 1 week postoperatively of septic shock related to the implantation (0.9% perioperative mortality). During folloiv-up of 16 ± 11 months, 45% of the patients had an event detected as ventricular tachycardia; 26% of these detections were felt clinically to be due to supraventricular rhythms. Of the remainder, 87% were successfully treated with the first VT therapy, and 98% were terminated by the final therapy; 66% of the patients had at least one episode of ventricular fibrillation, of which 5% were felt to be inappropriate detections; 65% of the appropriate episodes were successfully treated with the first VF therapy, and all were converted by the final therapy. Total mortality at 6, 12, and 24 months was 3%, 11%, and 19% respectively. Only one patient had sudden cardiac death, occurring at 13 months postimplant. Overall, the non-thoracotomy lead system for this ICD displayed infrequent implant complications and proved to be reliable ai terminating arrhythmias and maintaining a low rate of sudden cardiac death in this high risk popuiation.     

Intracellular targeting and protein kinase C in vascular smooth muscle cells: specific effects of different membrane-bound receptors

Protein kinase C is an important second messenger system, which is translocated from the cytosol to the cell membrane upon cell stimulation. We used confocal microscopy to study the spatial distribution of protein kinase C isoforms after stimulation of cultured vascular smooth muscle cells with different agonists. First, we analysed the effects of angiotensin II and platelet-derived growth factor (PDGF). Confocal microscopy showed a rapid assembly of PKC α along cytosolic fibres followed by a translocation towards the nucleus with angiotensin II. PDGF engendered a similar, but much slower response; however, a cytoskeletal distribution was not observed. We then investigated the effects of thrombin and bFGF on nuclear translocation. bFGF induced a rapid translocation of the isoform towards the perinuclear region and into the nucleus. bFGF had a similar effect on PKC ?. In contrast, thrombin had a smaller effect on nuclear translocation of PKC α and did not influence PKC ?, but instead induced a rapid nuclear translocation of PKC ζ. Thus, tyrosine kinase receptor activation via bFGF induces a rapid association of PKC α and ? within nuclear structures. Our results show that agonists cause, not only a translocation of protein kinase C isoforms into the cell membrane but also into the cell nucleus. Lastly, we analyzed the nuclear immunoreactivity of the PKC isoforms α, δ,? and ζ in vascular smooth muscle cells during the cell cycle. Resting cells were stimulated with foetal calf serum (FCS, 10%), which translocated PKC α and ? to the perinuclear region and into the nucleus, while PKC δ and ζ showed no increase in nuclear immunoreactivity. After 4 h of FCS, the nuclear immunoreactivity for PKC α and ? was reduced to or below control values. At 8 h, increased nuclear expression of isoforms α,? and ζ was observed, while isoform δ was not affected. Our results demonstrate a complex spatial and temporal regulation of PKC isoforms in response to vasoactive hormones and growth factors. We suggest that protein kinase C may be important for nuclear signaling and demonstrate that nuclear translocation of PKC isoforms is differentially regulated during the cell cycle.     

Quadruple Pads Approach for External Cardioversion of Atrial Fibrillation

MARROUCHE, N.F., et al. : Quadruple Pads Approach for External Cardioversion of Atrial Fibrillation. This study examined the alternative of transthoracic quadruple pads shock delivery of two simultaneous 360-J shocks to convert refractory AF in patients failing standard external cardioversion. Forty-six patients (  mean age 58 ± 11 years, 23 men  ) with chronic AF (  duration 14 ± 17 months, range 1–60 months  ) were included. The left atrial diameter was  47 ± 7 mm  . The left ventricular ejection fraction was  59 ± 11%  . Antiarrhythmic drugs had failed to convert 44 (96%) of these patients. All patients underwent conventional external transthoracic cardioversion with pads applied in the antero-apical position using energy settings of 200 and 360 J, consecutively. In all patients who failed conventional cardioversion, quadruple pads were applied. Quadruple pads consisted of four pads, two in the antero-posterior position and two in a second apex-posterior position. Standard cardioversion to sinus rhythm was successful in 19 (41%) patients after use of a single 200-J shock and an additional 8 (17%) after a single 360-J shock. The total success rate was 58% after conventional cardioversion. The quadruple pads were successful in 14 (74%) of the remaining 19 patients. Four of the five patients who failed the quadruple pads approach subsequently also failed internal cardioversion. Thus, the cardioversion success rate was increased from 48% using the conventional approach to 89% using the quadruple pads approach. Quadruple pads external cardioversion is highly effective in converting chronic AF refractory to standard shock protocols to sinus rhythm. Moreover, the failure of the quadruple pads approach seems to predict poor response to internal cardioversion.     

Day to day variations in morphology and duration of fragmented ventricular potentials during the late post-myocardial infarction phase in conscious dogs

The relationship between the inducibility of ventricular tachyarrhythmiasand the presence of fractionated epicardial ventricular electrograms(‘late potentials’) was studied daily between days3 and 8 after experimental myocardial infarction in 15 consciousdogs. Before each programmed stimulation, epicardial infarctzone electrograms were recorded from implanted ‘composite’electrodes during sinus rhythm. There was considerable dailyvariation in the morphology and duration of delayed ventricularactivation, but no significant difference in duration of infarctzone electrograms was seen between studies resulting in ventricularfibrillation (108±62ms, mean±SD), sustained ventriculartachycardia (87±18ms), nonsustained (94 ±41 ms)or no tachycardia (78±5 ms). Although fractionated ventricularelectrograms were commonly recorded early after infarction,their presence and duration could not predict the inducibilityof malignant ventricular tachyarrythmias. Similar limitationsmay apply in clinical practice to the use of surface signalaveraging of ventricular late potentials in the early post-myocardialinfarction period.     

Intraindividual comparison of intravenous ajmaline and quinidine in patients with sustained ventricular tachycardia: Effects on normal myocardium and on arrhythmia characteristics

Intraindividual comparison of the acute response to intravenousquinidine and to intravenous ajmaline was performed in 23 patientswith sustained ventricular tachycardia (VT) who underwent serialelectrophysiological studies. In each patient, sustained VTcould be reproducibly initiated by programmed ventricular stimulationduring control studies. Inducibility of sustained VT was preventedafter quinidine in 6 of the 23 patients (26%) and after ajmalinein 8 of the same 23 cases (35%). Agreement between the effectsof both drugs was not significant: 2 patients had a similarresponse to both quinidine and ajmaline and 11 patients didnot have a response to either of the two drugs, resulting ina total of only 13 patients (57%) who had a similar responseto both drugs.In the 11 non-responders with inducible sustainedVT before and after both drugs, quinidine and ajmaline causedqualitatively and quantitatively similar alterations of VT characteristicsincluding a significant prolongation of the interval betweenthe initiation extrastimulus and the first beat of VT by 38and 42% (P<0.01), an increase in VT cycle length by 15 and22% (P<0.01) and a prolongation of the QRS duration duringVT by 15 and 18% (P<0.01), respectively. In all 23 patients,quinidine and ajmaline caused a quantitatively similar prolongationof ventricular refractoriness by 11 and 9% (P<0.05), of theQRS duration at sinus rhythm by 10 and 15% (P<0.01) and ofthe QTc interval by 13 and 10% (P<0.05), respectively. Thus,ajmaline and quinidine appear to have similar electrophysiologicaleffects on both normal myocardiumand on indirect parametersof reentry; in individual patients with sustained VT, however,such electrophysiological similarities do not result in significantagreement of preventive responses.     

Esophageal Acid Levels after Pulmonary Vein Isolation for Atrial Fibrillation

Background: Pulmonary vein antrum isolation (PVAI) is a potentially curative, nonpharmacologic treatment of atrial fibrillation (AF). Several procedural complications have been described, including esophageal wall lesions ranging from erythema and esophagitis, necrosis and ulcer, to atrio-esophageal fistula. We prospectively studied changes in esophageal acid levels before and after PVAI.
Methods: We performed 24-hour pH-metry before and 1.3 ± 1.6 days after PVAI, in 25 patients (mean age = 62 ± 12 years, 17 men) with symptomatic AF. A 2-mm transnasal probe was inserted into the inferior part of the esophagus and into the stomach to measure pH levels at fixed intervals. DeMeester scores, indicating acidic gastro-esophageal reflux, were calculated.
Results: The mean number of reflux episodes increased from 89 ± 80 before to 107 ± 94 after PVAI. The mean percentage of time with esophageal pH < 4 was shorter after (108 ± 193 minutes) than before PVAI (159 ± 245 minutes). The mean DeMeester score decreased from 49 ± 68 before to 31 ± 41 after PVAI (P < 0.05). We observed erythema or esophagitis in five patients, necrosis or ulcer in seven, and atrio-esophageal fistula in no patient.
Conclusions: Our hypothesis of increased acid levels caused by stimulation of the right vagal nerve during isolation of the right upper pulmonary vein was not verified.     

Monoclonal antibodies specific for human cardiac myosin: selection, characterization and experimental myocardial infarct imaging

Radiolabelled anti-myosin antibodies (AM Ab) specifically accumulatein necrotizing myocytes and, therefore, allow the scintigraphicdetection of myocardial infarction. In order to provide a constantsupply of myosin-specific antibodies, the somatic cell fusiontechnique was used for the selection and propagation of A MAb. Out of 126 antibody producing cell lines, nine were selectedfor further subcloning, due to their high affinity for purifiedmyosin. For the in vivo imaging, two IgG-antibody moleculesappeared particularly useful based on their antigenic specificityas assessed by immunoblotting and indirect immunofluorescencetechnique. After radiolabelling with iodine-123, undigestedantibody molecules or their Fab fragments were injected into10 dogs with experimental myocardial infarction. The accumulationof radioactivity in myocardial infarction was assessed by invivo imaging and in vitro scintigraphy of ventricular slicesstained by tetrazolium. The use of undigested AM Ab resultedin a high uptake ratio of radioactivity in the infarcted ascompared to normal myocardium (20: 1). In vivo infarct imaging,however, was not possible due to sustained labelling of theblood pool. The uptake ratio of iodine-123 labelled Fab fragmentswas only 9 1, but due to a faster plasma clearance of the Fabfragments, uptake in the heart could be visualized 5 h afterintravenous injection. Clear differentiation between infarctedand noninfarcted myocardium, however, was limited by accumulationof radioactivity in the thoracotomy wound, in the liver, andin the stomach.     

Intracardiac Echocardiography Improves Procedural Efficiency During Cryoballoon Ablation for Atrial Fibrillation: A Pilot Study

Intracardiac Echocardiography Guided Cryoballoon Ablation. Background: Cryoballoon ablation is increasingly used for pulmonary vein isolation (PVI) in patients with atrial fibrillation (AF). This new technique aims to perform PVI safer and faster. However, procedure and fluoroscopy times were similar to conventional RF approaches. We compared ICE plus fluoroscopy versus fluoroscopy alone for anatomical guidance of PVI. Methods: Forty‐three consecutive patients with paroxysmal AF were randomly assigned to ICE plus fluoroscopy (n = 22) versus fluoroscopy alone (n = 21) for guidance of cryoballoon PVI. A “single big balloon” procedure using a 28 mm cryoballoon was performed. The optimal ICE‐guided position of the cryoballoon was assessed by full ostial occlusion and loss of Doppler coded reflow to the left atrium (LA). Any further freezes were ICE‐guided only without use of fluoroscopy or contrast media injection. Results: A total of 171 pulmonary veins could be visualized with ICE. 80% of ICE‐guided freezes were performed with excellent ICE quality. Acute procedural success and AF recurrence rate at 6 months were similar in both groups (AF recurrence: ICE‐guided = 27% vs Fluoroscopy = 33%; P = ns). Patients without ICE guidance had significantly longer procedure (143 ± 27 minutes vs 130 ± 19 minutes; P = 0.05) and fluoroscopy times (42 ± 13 minutes vs 26 ± 10, P = 0.01). The total amount of contrast used during the procedure was significantly lower in patients with ICE guidance (88 ± 31 mL vs 169 ± 38 mL, P < 0.001). Conclusion: Additional ICE guidance appears to be associated with lower fluoroscopy, contrast, and procedure times, with similar efficacy rates. Specifically, ICE allows for better identification of the PV LA junction and more precise anatomically guided cryoballoon ablations. (J Cardiovasc Electrophysiol, Vol. 21, pp. 1202‐1207, November 2010)