Short-Long Heart Rate Variation Increases Dispersion of Action Potential Duration in Long QT Type 2 Transgenic Rabbit Model.

The initiation of polymorphic ventricular tachycardia in long QT syndrome type 2 (LQT2) has been associated with a characteristic ECG pattern of short-long RR intervals. We hypothesize that this characteristic pattern increases APD dispersion in LQT2, thereby promoting arrhythmia. We investigated APD dispersion and its dependence on two previous cycle lengths (CLs) in transgenic rabbit models of LQT2, LQT1, and their littermate controls (LMC) using random stimulation protocols. The results show that the short-long RR pattern was associated with a larger APD dispersion in LQT2 but not in LQT1 rabbits. The multivariate analyses of APD as a function of two previous CLs (APDn = C + α1CLn-1 + α2CLn-2) showed that α1 (APD restitution slope) is largest and heterogeneous in LQT2 but uniform in LQT1, enhancing APD dispersion under long CLn-1 in LQT2. The α2 (short-term memory) was negative in LQT2 while positive in LQT1, and the spatial pattern of α1 was inversely correlated to α2 in LQT2, which explains why a short-long combination causes a larger APD dispersion in LQT2 but not in LQT1 rabbits. In conclusion, short-long RR pattern increased APD dispersion only in LQT2 rabbits through heterogeneous APD restitution and the short-term memory, underscoring the genotype-specific triggering of arrhythmias in LQT syndrome.

Protamine to expedite vascular hemostasis after catheter ablation of atrial fibrillation: A randomized controlled trial.

BACKGROUND: There are no randomized controlled studies of the efficacy and safety of protamine to reverse anticoagulant effects of heparin after catheter ablation (CA) of atrial fibrillation (AF). OBJECTIVE: The purpose of this study was to determine the efficacy and safety of protamine to expedite vascular hemostasis and ambulation after CA of AF. METHODS: CA to eliminate AF (n = 139) or left atrial flutter (n = 11) was performed in 150 patients using radiofrequency catheter ablation (n = 112) or cryoballoon ablation (n = 38). CA was performed under uninterrupted anticoagulation with warfarin in 28 patients or after skipping a single dose of a novel oral anticoagulant in 122 patients who were randomized to receive protamine (n = 77) or to the control group (n = 73). Baseline and procedural characteristics were similar between the 2 groups. Hemostasis was achieved manually once the activated clotting time returned to preprocedural values. RESULTS: The maximum activated clotting time during CA was 359 ± 31 and 359 ± 29 seconds in the protamine and control groups, respectively (P = .91). The time to hemostasis was 123 ± 95 minutes in the protamine group and 260 ± 70 minutes in the control group (P < .001). The time to ambulation was 316 ± 80 and 480 ± 92 minutes in the protamine and control groups, respectively (P < .001). There were no differences in the rates of major or minor vascular access complications or thromboembolic events (P > .05). CONCLUSION: Protamine expedites vascular hemostasis and time to ambulation by ∼3 hours after CA of AF without an increase in the risk of vascular or thromboembolic complications.

Spatially Discordant Alternans and Arrhythmias in Tachypacing-Induced Cardiac Myopathy in Transgenic LQT1 Rabbits: The Importance of IKs and Ca2+ Cycling.

BACKGROUND: Remodeling of cardiac repolarizing currents, such as the downregulation of slowly activating K+ channels (IKs), could underlie ventricular fibrillation (VF) in heart failure (HF). We evaluated the role of Iks remodeling in VF susceptibility using a tachypacing HF model of transgenic rabbits with Long QT Type 1 (LQT1) syndrome. METHODS AND RESULTS: LQT1 and littermate control (LMC) rabbits underwent three weeks of tachypacing to induce cardiac myopathy (TICM). In vivo telemetry demonstrated steepening of the QT/RR slope in LQT1 with TICM (LQT1-TICM; pre: 0.26±0.04, post: 0.52±0.01, P<0.05). In vivo electrophysiology showed that LQT1-TICM had higher incidence of VF than LMC-TICM (6 of 11 vs. 3 of 11, respectively). Optical mapping revealed larger APD dispersion (16±4 vs. 38±6 ms, p<0.05) and steep APD restitution in LQT1-TICM compared to LQT1-sham (0.53±0.12 vs. 1.17±0.13, p<0.05). LQT1-TICM developed spatially discordant alternans (DA), which caused conduction block and higher-frequency VF (15±1 Hz in LQT1-TICM vs. 13±1 Hz in LMC-TICM, p<0.05). Ca2+ DA was highly dynamic and preceded voltage DA in LQT1-TICM. Ryanodine abolished DA in 5 out of 8 LQT1-TICM rabbits, demonstrating the importance of Ca2+ in complex DA formation. Computer simulations suggested that HF remodeling caused Ca2+-driven alternans, which was further potentiated in LQT1-TICM due to the lack of IKs. CONCLUSIONS: Compared with LMC-TICM, LQT1-TICM rabbits exhibit steepened APD restitution and complex DA modulated by Ca2+. Our results strongly support the contention that the downregulation of IKs in HF increases Ca2+ dependent alternans and thereby the risk of VF.

Guidewire-induced coronary artery perforation and tamponade during PCI: in-hospital outcomes and impact on long-term survival.

BACKGROUND: Guidewire-induced coronary perforation (CP) rate is reported to have increased. METHODS: We analyzed 23,399 PCIs and identified 73 patients complicated by CP, of which 31 were guidewire induced. Patients were divided into two groups: group A (guidewire-induced CP) and group B (non-guidewire induced CP). Characteristics and outcomes were compared and a multivariate model was developed to evaluate the independent contribution of guidewire-induced CP on mortality. RESULTS: Group A patients had more PCIs on CTO lesions (P=.001). Group A showed a trend for higher tamponade (P=.08). Delayed tamponade occurred only in group A (P<.001). Polytetrafluoroethylene stents were used more often in group B (P<.01). In-hospital mortality was similar between groups (3.2% vs. 7.1%; P=NS). Emergent cardiac surgery was needed in 5.5% of all CP patients and was similar between groups. Group A had a trend for better survival (hazard ratio [HR], 0.37; 95% CI, 0.12-1.10; P=.07). Tamponade conferred a 3-fold increase in the long-term probability of death (HR, 2.95; 95% CI, 1.07-8.13; P=.04). Guidewire-induced CP during elective PCI had the best survival (HR, 0.31; 95% CI, 0.11-0.87; P=.03). CONCLUSIONS: Guidewire-induced CP rate is low. In-hospital mortality was similar for patients with guidewire-induced and non-guidewire induced perforations. Presentation of tamponade was occasionally delayed and associated with increased early and late death. Percutaneous coronary intervention of lesions with an expected increased risk of CP should be undertaken with consideration of the short- and long-term risk, particularly during non-elective PCI since tamponade in this setting increased the risk of late death by nearly 3-fold.

Delayed perforation after percutaneous coronary intervention: rare and potentially lethal.

INTRODUCTION: Cardiac tamponade is a grave but fortunately uncommon complication of percutaneous coronary intervention (PCI). Few studies have specifically addressed angiographic characteristics and outcomes associated with delayed cardiac tamponade after PCI. With the current study we tried to define the incidence of this complication and to characterize the events in order to improve our understanding of the likely mechanisms. METHODS/RESULTS: We reviewed 23,399 PCIs performed at our institution during an 8-year period (1999-2006) and we present 10 cases of delayed tamponade. A brief description of each case is provided and findings from retrospective review of the coronary angiography, as well as features of PCI complexity are presented. Also, we summarize the procedural characteristics and outcomes. Delayed perforations are rare and possibly preventable. They usually occur after complex interventions and mostly attributed to distal wire perforations. Surgical intervention is needed less often today than before. Successful pericardiocentesis is of paramount importance. CONCLUSIONS: The potential lethal outcome associated with delayed tamponade emphasizes the importance of taking steps to prevent this complication. First, prevention and, second, prompt treatment should be the goal, with the use of appropriate technique, clinical awareness, and vigilance.

Cardiac tamponade complicating coronary perforation during angioplasty: short-term outcomes and long-term survival.

BACKGROUND: Cardiac tamponade constitutes the most severe clinical consequence of a coronary perforation (CP) during percutaneous coronary intervention (PCI). METHODS: We analyzed 23,399 PCIs and identified 73 patients complicated by CP (0.31%), of which 26 developed tamponade (0.11%). Patients were divided into two groups: CP with tamponade (group A) and CP without tamponade (group B). Characteristics and outcomes were compared and a multivariate model was developed to evaluate the independent contribution of tamponade on mortality. RESULTS: All patients with tamponade were treated with pericardiocentesis. Tamponade increased the risk of death by more than 3-fold (odds ratio [OR] = 3.3; 95% confidence interval [CI],1.01-10.6; P=.047) relative to patients with CP but no tamponade. CP with tamponade during non-elective PCI carried a significantly worse long-term prognosis (P=.001) than the same complications during elective PCI. The use of glycoprotein IIb/IIIa inhibitors and bivalirudin did not differ between groups. Polytetrafluoroethylene-covered stents were used similarly between the two groups, while coil embolization was used more often in group A (P=.003). Emergent cardiac surgery was needed in 3 patients (11.5%) in group A versus 1 patient (2.1%) in group B. CONCLUSIONS: Tamponade complicating CP during PCI has short- and long-term major adverse effects. In-hospital mortality after tamponade and referral for emergent surgical treatment have decreased. Nonetheless, tamponade in this setting increases risk of death by >3-fold. PCI of complex lesions with an expected increased risk of perforation should be undertaken cautiously among patients with non-elective PCI because of increased early and late risk of death.