Tack Ki Leung

Feasibility of cardiac cryoablation using a transvenous steerable electrode catheter

We investigated the feasibility of using cryogenic technology in an electrode catheter for percutaneous ablation of cardiac tissue. Despite its high success rate, radiofrequency catheter ablation has important limitations especially with regards to the treatment of ventricular arrhythmias associated with a chronic scar. Arrhythmia surgery experience has shown that freezing with a hand held probe can permanently ablate the arrhythmogenic substrate of ventricular tachycardia associated with an old scar. Moreover, cryosurgery also allows for reversible “ice mapping,” in which the area likely responsible for the arrhythmia can be evaluated by suppressing its electrophysiologic properties prior to the creation of an irreversible state. A new steerable cryoablation catheter using Halocarbon 502 as a refrigerant was utilized in six dogs. Serial cryoapplications were performed in the right and left ventricles. In two dogs, we attempted reversible ice mapping of the AV node. Pathological evaluation of the lesions was done acutely in all the animals. Forty-two cryoapplications were delivered at a mean temperature of −45 ± 9.8°C. No lesion was found at pathological evaluation for 16 cryoapplications which did not achieve a temperature of less (colder) than −30°C. The remaining applications resulted in 26 lesions which were hemorrhagic and sharply demarcated from normal myocardium. Histological evaluation revealed contraction band necrosis. Reversible ice mapping of the AV node was successfully achieved in two animals. Cryoablation is feasible using an electrode catheter with multiple electrodes. This technology has the potential to allow for reversible ice mapping to confirm a successful ablation target before definitive ablation.

Atrial Ischemia Promotes Atrial Fibrillation in Dogs

Background—Coronary artery disease is a significant risk factor for atrial fibrillation (AF), but the basis for this association is incompletely understood. The present study evaluated the hypothesis that atrial ischemia can create a substrate for AF maintenance. Methods and Results—Atrial ischemia was induced by occlusion of an atrial arterial branch that did not provide blood flow to the ventricles. Atrial-arterial occlusion increased the duration of AF induced by burst pacing from 57±32 seconds (control) to 803±214 seconds (P <0.001) after 0.5 hour of occlusion and to 887±209 seconds (P <0.001) after 3 hours of occlusion. Prolonged AF (>20 minutes) was induced in 0 of 16 dogs (0%) under control conditions, 7 of 16 (44%, P <0.01) at 0.5 to 3 hours, and 5 of 13 (38%, P <0.01) 3 to 5 hours after occlusion. Atrial conduction was slowed substantially within the ischemic zone: eg, conduction delay was 8±1 ms at a cycle length of 200 ms, control, versus 22±5 ms (P <0.01) after 0.5 hours and 27±5 ms (P <0.001) after 3 hours of ischemia. Refractoriness was initially unaffected but was prolonged 5 hours after occlusion. Phase-delay analysis and high-density mapping confirmed severe conduction slowing in the ischemic zone. Histological examination confirmed the location of ischemic regions and revealed extensive ischemia-induced necrosis at sites of conduction delay. Conclusions—Experimental atrial ischemia creates a substrate for AF maintenance, apparently by causing local conduction slowing that promotes reentry. These results suggest that atrial ischemia may significantly promote AF, and may be relevant to AF mechanisms in association with coronary artery disease.

Dissociation Between Ionic Remodeling and Ability to Sustain Atrial Fibrillation During Recovery From Experimental Congestive Heart Failure

Background—Congestive heart failure (CHF) downregulates atrial transient outward (Ito), slow delayed rectifier (IKs), and L-type Ca2+ (ICa,L) currents and upregulates Na+-Ca2+ exchange current (INCX) (ionic remodeling) and causes atrial fibrosis (structural remodeling). The relative importance of ionic versus structural remodeling in CHF-related atrial fibrillation (AF) is controversial. Methods and Results—We measured hemodynamic and echocardiographic parameters, mean duration of burst pacing–induced AF (DAF), and atrial-myocyte ionic currents in dogs with CHF induced by 2-week ventricular tachypacing (240 bpm), CHF dogs allowed to recover without pacing for 4 weeks (REC), and unpaced controls. Left ventricular ejection fraction averaged 58.6±1.2% (control), 36.2±2.3% (CHF, P <0.01), and 57.9±1.6% (REC), indicating full hemodynamic recovery. Similarly, left atrial pressures were 2.2±0.3 (control), 13.1±1.5 (CHF), and 2.4±0.4 (REC) mm Hg. CHF reduced Ito density by ≈65% (P <0.01), decreased ICa,L density by ≈50% (P <0.01), and diminished IKs density by ≈40% (P <0.01) while increasing INCX density by ≈110% (P <0.05). In REC, all ionic current densities returned to control values. DAF increased in CHF (1132±207 versus 14.3±8.8 seconds, control) and remained increased with REC (1014±252 seconds). Atrial fibrous tissue content also increased in CHF (2.1±0.2% for control versus 10.2±0.7% for CHF, P <0.01), with no recovery observed in REC (9.4±0.8%, P <0.01 versus control, P =NS versus CHF). Conclusions—With reversal of CHF, there is complete recovery of ionic remodeling, but the prolonged-AF substrate and structural remodeling remain. This suggests that structural, not ionic, remodeling is the primary contributor to AF maintenance in experimental CHF.

Transvenous Catheter Ice Mapping and Cryoablation of the Atrioventricular Node in Dogs

While radiofrequency catheter ablation is very effective, it does not allow for prediction of success prior to full delivery of the energy. We investigated the use of cryoablation using a new catheter on the AV node to determine (1) if a successful site might be identified prior to the ablation itself, and (2) the parameters of cryoablation of the AV node using a new cryocatheter. In eight dogs, the cryoablation catheter was advanced to the AV node to produce transient high degree AV block by lowering the temperature to a minimum of −40°C (ice mapping). Transient high degree AV node block was obtained in seven of eight animals at a mean temperature of −39.9 ± 11.6°C. No significant pathological modification was found in all animals but one and, in all cases, electrophysiological parameters of the A V node measured before, 20 minutes, 60 minutes, and up to 56 days after cryoapplication were not significantly different. In the 12 other dogs, after ice mapping, cryoablation of the A V node was attempted with a single freeze‐thaw cycle in 6 dogs (group 1) and a double freeze‐thaw cycle in the other 6 dogs (group II). Chronic complete AV block was obtained in only one animal in group I compared to all animals in group II. Ablation of the A V node is effective with a double freeze‐thaw cycle using a percutaneous catheter cryoablation system. Ice mapping of the area allows for identification of the targeted site.

Atrial Tachycardia Remodeling of Pulmonary Vein Cardiomyocytes Comparison With Left Atrium and Potential Relation to Arrhythmogenesis

Background—The pulmonary veins (PVs) are important in the pathophysiology of atrial fibrillation (AF), as is atrial tachycardia (AT) remodeling. The relative importance of AT remodeling in PVs versus other atrial sites is unknown. The present study assessed AT-induced cellular changes in PVs versus left atrium (LA) and their relationship to arrhythmogenesis. Methods and Results—We studied ionic currents (single-cell patch clamp) and action potentials (APs; coronary-perfused multicellular preparations) in the PVs and LA free wall of dogs after 7-day AT pacing (400 bpm), as well as in nonpaced control dogs. In controls, rapid (IKr) and slow (IKs) delayed-rectifier currents were larger in PVs; transient-outward (Ito), inward-rectifier (IK1), and L-type Ca2+ (ICa) currents and AP duration were smaller. AT remodeling reduced ICa and Ito, left IKr and IKs unchanged, and increased IK1 in both LA and PV. AT reduced action potential duration in both LA and PV. LA–PV AP differences became smaller in AT than in control dogs. Premature extrastimuli induced atrial tachyarrhythmias at 4.5±2.8% (mean±SEM) sites in 6 control multicellular preparations compared with 64.2±7.3% sites in 9 AT-remodeled preparations (P<0.001). Resection of all PVs failed to alter atrial tachyarrhythmia inducibility in AT-remodeled preparations (67.5±13.1%). PV resection did not significantly change tachyarrhythmia duration (mean 3.9 seconds per heart, range 0.7 to 15.7 seconds before resection; mean 7.0 seconds per heart, range 0.9 to 36.0 seconds after resection) or cycle length (120±6 ms before resection, 115±8 ms after resection). Conclusions—AT produces qualitatively similar ionic remodeling in LA and PVs but reduces PV–LA AP differences. PVs are not essential for AT-induced atrial tachyarrhythmia promotion in this model, which may relate to the failure of PV isolation to prevent AF in some patient populations.

Coronary restenosis: evaluation of a restenosis injury index in a swine model.

To investigate the mechanisms of restenosis and detect useful interventions to prevent it, reliable quantitative measurements must be evaluated. Coronary arteries of domestic and minipigs (n = 18) were mechanically injured by balloon overstretching and killed at different intervals (2 to 25 weeks) after quantitative angiographic analysis. Morphometric measurements evaluated intimal hyperplasia at 0.59 +/- 0.42 mm without relation to artery size or balloon/artery ratio. Intimal hyperplasia, expressed as the ratio of neointimal area to total wall area (A), is directly related to the injury, assessed by the ratio of internal elastic lamina (IEL) fracture length to IEL circumference (B), r = 0.84, p = 0.002. Restenosis injury index, defined as A/B, provides a useful tool for the quantitative assessment of future angioplasty-related restenosis interventions.

The rat heart contains a neural stem cell population; Role in sympathetic sprouting and angiogenesis

Nestin-expressing cells were identified in the normal rat heart characterized by a small cell body and numerous processes and following an ischemic insult migrated to the infarct region. The present study was undertaken to identify the phenotype, origin and biological role of nestin-expressing cells during reparative fibrosis. A neural stem cell phenotype was identified based on musashi-1 expression, growth as a neurosphere, and differentiation to a neuronal cell. Using the Wnt1-cre; Z/EG transgenic mouse model, which expresses EGFP in embryologically-derived neural crest cells, the reporter signal was detected in nestin-expressing cells residing in the heart. In infarcted human hearts, nestin-expressing cells were detected in the viable myocardium and the scar and morphologically analogous to the population identified in the rat heart. Following either an ischemic insult or the acute administration of 6-hydroxydopamine, sympathetic sprouting was dependent on the physical association of neurofilament-M immunoreactive fibres with nestin-positive processes emanating from neural stem cells. To specifically study the biological role of the subpopulation in the infarct region, neural stem cells were isolated from the scar, fluorescently labelled and transplanted in the heart of 3-day post-MI rats. Injected scar-derived neural stem cells migrated to the infarct region and were used as a substrate for de novo blood vessel formation. These data have demonstrated that the heart contains a resident population of neural stem cells derived from the neural crest and participate in reparative fibrosis. Their manipulation could provide an alternative approach to ameliorate the healing process following ischemic injury.

Heart rate reduction by ivabradine reduces diastolic dysfunction and cardiac fibrosis.

Objectives: To determine if heart rate (HR) reduction with ivabradine (IVA), a selective inhibitor of the pacemaker If current, prevents cardiac dysfunction associated with dyslipidemia. Methods: New Zealand White rabbits received either a standard diet, a 0.5% cholesterol-enriched diet only (CD), or a 0.5% CD with IVA (17 mg/kg/day) for 12 weeks. HR, left ventricular (LV) systolic function, diastolic function and LV regional myocardial performance index (MPI) were studied using echocardiography. Histological analysis included cardiac interstitial fibrosis and collagen type I fibers. Plasma levels of angiotensin II and aldosterone were quantified by immunoassays. Results: IVA reduced HR by approximately 11%. IVA improved MPI and attenuated LV diastolic dysfunction (DD) (92% mild and 8% moderate DD with IVA vs. 54% mild and 46% moderate DD in CD group). IVA also reduced atrial fibrosis (p = 0.027), ventricular fibrosis (p = 0.0002) and ventricular collagen type I (p = 0.0042). IVA decreased plasma angiotensin II levels (p = 0.042), and both angiotensin II and aldosterone levels were correlated with HR (p = 0.038 and 0.008). Conclusion: Selective HR reduction with IVA reduces DD and cardiac fibrosis in hypercholesterolemic rabbits. These beneficial effects of IVA support testing pure HR reduction in patients with diastolic heart failure.

Increase in sudden death from coronary artery disease in young adults

BACKGROUND Sudden cardiac death (SCD) is the most common cause of death in adults aged <65 years, making it a major public health problem. A growing incidence in coronary artery disease (CAD) in young individuals has been predicted in developed countries, which could in turn be associated with an increase in SCD in this population. The aim of the study was to assess the prevalence of CAD among autopsies of young individuals (<40 years) who had sudden death (SD). METHODS We selected all the autopsies referred to the Montreal Heart Institute and Maisonneuve-Rosemont Hospital from January 2002 to December 2006 that corresponded to individuals <40 years old who had died suddenly. For each decedent, the following data were collected: cause of death, autopsy findings, available clinical history, toxicological findings, and cardiovascular risk factors. RESULTS From a total of 1,260 autopsies, 243 fulfilled the inclusion criteria. Coronary artery disease was the main cause of SCD from age 20 years, representing the 37% of deaths in the group of 21 to 30 years old, and up to 80% of deaths in the group of 31 to 40 years old. Among individuals who died of CAD, 3-vessel disease was observed in 39.7% of cases. Moreover, among the whole population <40 years old, at least 1 significant coronary lesion was observed in 39.5% of cases, irrespective to the cause of death. In the multivariable analysis, an increased BMI (hazard ratio 1.1 for each kg/m(2), 95% CI 1.01-1.1) and hypercholesterolemia (hazard ratio 2.4, 95% CI 1.7-333.3) showed to be the modifiable factors related to an increased risk of SD from CAD. CONCLUSIONS In our population, CAD was the main cause of SD from age 20 years. These data bring into question whether present prevention strategies are sufficient and reinforce the need to extend prevention to younger ages.

Incidence and outcome of radial artery infections following cardiac surgery

BACKGROUND Radial artery infections secondary to catheterization for blood pressure monitoring are rare but potentially serious complications. The objective of the study was to evaluate the incidence, the risk factors and the evolution of radial artery infections following cardiac surgery. METHODS A retrospective review of 8300 patients undergoing cardiac surgery between 1998 and 2002 at the Montreal Heart Institute (MHI) was undertaken. All patients with superficial radial artery infections, infected radial artery pseudoaneurysms, and arterial catheter-related bacteremia were considered using prospective global surveillance of all nosocomial infections over the study period by an infection control nurse. RESULTS Thirteen patients with radial infections were encountered (0.2%) with bacteremia occurring in 9 patients (0.15%). Five patients developed infected radial artery pseudoaneurysms (0.05%) and 5 patients developed subsequent sternal wound infections. Two patients died in their early postoperative evolution. Mean patient age was 67 years old and mean duration of cannulation was 5.8 days. Only 1 patient had diabetes. Seven of 13 patients were positive for Staphylococcus aureus (54%). All patients had undergone cardiopulmonary bypass (CPB) for various procedures. All superficial infections responded well to antibiotic therapy. Early surgical intervention is essential in cases of infected radial artery pseudoaneurysms. CONCLUSIONS The postoperative state and cardiopulmonary bypass put patients at risk for infectious complications. Strict systematic changing of arterial lines on a timely basis is unwarranted in our opinion. A high suspicion index, aggressive surgical treatment of bacterial arteritis and appropriate intravenous antibiotics are essential to improve the prognosis.