Bipolar ablation for deep intra-myocardial circuits: human ex vivo development and in vivo experience.

To access publisher's full text version of this article click on the hyperlink at the bottom of the pageCurrent conventional ablation strategies for ventricular tachycardia (VT) aim to interrupt reentrant circuits by creating ablation lesions. However, the critical components of reentrant VT circuits may be located at deep intramural sites. We hypothesized that bipolar ablations would create deeper lesions than unipolar ablation in human hearts.Ablation was performed on nine explanted human hearts at the time of transplantation. Following explant, the hearts were perfused by using a Langendorff perfusion setup. For bipolar ablation, the endocardial catheter was connected to the generator as the active electrode and the epicardial catheter as the return electrode. Unipolar ablation was performed at 50 W with irrigation of 25 mL/min, with temperature limit of 50°C. Bipolar ablation was performed with the same settings. Subsequently, in a patient with an incessant septal VT, catheters were positioned on the septum from both the ventricles and radiofrequency was delivered with 40 W. In the explanted hearts, there were a total of nine unipolar ablations and four bipolar ablations. The lesion depth was greater with bipolar ablation, 14.8 vs. 6.1 mm (P < 0.01), but the width was not different (9.8 vs. 7.8 mm). All bipolar lesions achieved transmurality in contrast to the unipolar ablations. In the patient with a septal focus, bipolar ablation resulted in termination of VT with no inducible VTs.By using a bipolar ablation technique, we have demonstrated the creation of significantly deeper lesions without increasing the lesion width, compared with standard ablation. Further clinical trials are warranted to detail the risks of this technique

Regional ion channel gene expression heterogeneity and ventricular fibrillation dynamics in human hearts

RATIONALE: Structural differences between ventricular regions may not be the sole determinant of local ventricular fibrillation (VF) dynamics and molecular remodeling may play a role. OBJECTIVES: To define regional ion channel expression in myopathic hearts compared to normal hearts, and correlate expression to regional VF dynamics. METHODS AND RESULTS: High throughput real-time RT-PCR was used to quantify the expression patterns of 84 ion-channel, calcium cycling, connexin and related gene transcripts from sites in the LV, septum, and RV in 8 patients undergoing transplantation. An additional eight non-diseased donor human hearts served as controls. To relate local ion channel expression change to VF dynamics localized VF mapping was performed on the explanted myopathic hearts right adjacent to sampled regions. Compared to non-diseased ventricles, significant differences (p<0.05) were identified in the expression of 23 genes in the myopathic LV and 32 genes in the myopathic RV. Within the myopathic hearts significant regional (LV vs septum vs RV) expression differences were observed for 13 subunits: Nav1.1, Cx43, Ca3.1, Cavalpha2delta2, Cavbeta2, HCN2, Na/K ATPase-1, CASQ1, CASQ2, RYR2, Kir2.3, Kir3.4, SUR2 (p<0.05). In a subset of genes we demonstrated differences in protein expression between control and myopathic hearts, which were concordant with the mRNA expression profiles for these genes. Variability in the expression of Cx43, hERG, Na(+)/K(+) ATPase ss1 and Kir2.1 correlated to variability in local VF dynamics (p<0.001). To better understand the contribution of multiple ion channel changes on VF frequency, simulations of a human myocyte model were conducted. These simulations demonstrated the complex nature by which VF dynamics are regulated when multi-channel changes are occurring simultaneously, compared to known linear relationships. CONCLUSIONS: Ion channel expression profile in myopathic human hearts is significantly altered compared to normal hearts. Multi-channel ion changes influence VF dynamic in a complex manner not predicted by known single channel linear relationships

Early and long-term outcomes after manual and remote magnetic navigation guided catheter ablation for ventricular tachycardia

Aims Remote magnetic navigation (RMN) is a safe and effective means of performing ventricular tachycardia (VT) ablation. It may have advantages over manual catheter ablation due to ease of manoeuvrability and catheter stability. We sought to compare the safety and efficacy of RMN vs. manual VT ablation. Methods and results Retrospective study of procedural outcomes of 139 consecutive VT ablation procedures (69 RMN, 70 manual ablation) in 113 patients between 2009 and 2015 was performed. Remote magnetic navigation was associated with overall higher acute procedural success (80% vs. 60%, P = 0.01), with a trend to fewer major complications (3% vs. 9% P = 0.09). Seventy-nine patients were followed up for a median of 17.0 [interquartile range (IQR) 3.0–41.0] months for the RMN group and 15.5 (IQR 6.5–30.0) months for manual ablation group. In the ischaemic cardiomyopathy subgroup, RMN was associated with longer survival from the composite endpoint of VT recurrence leading to defibrillator shock, re-hospitalization or repeat catheter ablation and all-cause mortality; single-procedure adjusted hazard ratio (HR) 0.240 (95% CI 0.070–0.821) P = 0.023, multi-procedure HR 0.170 (95% CI 0.046–0.632) P = 0.002. In patients with implanted defibrillators, multi-procedure VT-free survival was superior with RMN, HR 0.199 (95% CI 0.060–0.657) P = 0.003. Conclusion Remote magnetic navigation may improve clinical outcomes after catheter ablation of VT in patients with ischaemic cardiomyopathy. Further prospective clinical studies are required to confirm these findings

Long Term Outcomes with Selective Drug Eluting Stent Use in STElevation Myocardial Infarction in an Australian Urban Population

Aim: To evaluate the safety and effect on long-term outcomes of an approach that selectively uses drug-eluting stent (DES) only in ST elevation myocardial infarction (STEMI) that meet criteria for high risk of in-stent restenosis (ISR).Methods: Consecutive patients (n=1832) presenting with STEMI to a single large centre between April 2004 and January 2012 were managed according to an algorithm in which those with pre-specified criteria indicating they were at high risk for ISR received DES (46%, n=847), and otherwise received bare metal stents (BMS) (54%, n=985). High risk criteria included: vessel diameter £2.5mm (£3.0mm in diabetic patients); lesion length &gt;18mm; previous ISR; saphenous vein graft lesions; ostial lesions; bifurcation lesions; left main coronary artery lesions; and multi-vessel disease. The two groups were compared for primary composite outcome of major adverse cardiac events (MACE) including death, repeat MI and TVR; and secondary outcomes of target lesion revascularisation (TLR) and stent thrombosis (ST).Results: Over a median period of 24 months there was no significant difference (DES vs BMS) in MACE (13.6% vs 18.1%, p=0.074), mortality (7.6% vs 10.5%, p=0.327) or definite stent thrombosis (2.6% vs 1.6%, p=0.094). Patients who received DES had a lower rate of clinically driven TLR (1.6% vs 3.9%, p=0.032).Conclusion: An approach of selectively using DES in STEMI patients at high risk of ISR provides satisfactory long-term outcomes while limiting the number of patients exposed to DES costs

Axillary vein access using ultrasound guidance, Venography or Cephalic Cutdown - What is the optimal access technique for insertion of pacing leads?

We reviewed the different approaches used for central vein access during insertion of cardiac implantable electronic devices. The benefits and hazards of each approach (cephalic vein cutdown, axillary vein cannulation using venography and ultrasound) are discussed. Each approach has its advantages and hazards that need to be considered for the individual patient and balanced against the skills of the operator. The benefits of ultrasound guided venous access in reducing radiation exposure to the patient and implanter, avoiding the need for angiographic contrast and in minimizing the risk of pneumothorax and inadvertent arterial puncture are highlighted. Trainees should be taught each approach to deal with patient variability. Ultrasound guidance should be considered as a mainstream option for most patients

ST-elevation myocardial infarction in a migrant population : a registry-based study of patient treatment and outcomes

Background: Internationally, a growing number of studies has identified race-related disparities in the presentation, treatment and outcomes of patients with ST-elevation myocardial infarction (STEMI). With a large migrant population, Australia presents a unique microcosm in which to study the impact of migrant status and ethnicity in STEMI patients. Aim: To investigate if first-generation migrants differed in presentation, treatment or outcomes following STEMI compared with the Australian-born population. Methods: We conducted a retrospective observational study using data from a clinician-initiated registry. The study involved 2154 patients who presented to 12 hospitals between 2004 and 2012. Our main outcome measures included time to reperfusion, 30-day mortality and complications. Results: Migrants (n = 1035, 48.8%) were more likely to be older (61 vs 58 years, P < 0.001), diabetic (29.3 vs 21.5%, P < 0.001) and have a prolonged symptom to door time (102 vs 91 min, P = 0.04). Despite lower rates of previous known ischaemic heart disease (22.5 vs 26.6%, P = 0.03), migrants had more diffuse disease (triple vessel or left main (3VD/LM): 29.8 vs 22.0%, P < 0.001) and higher troponin values (3.77 vs 3.22 μg/L, P = 0.01). We found no significant differences in hospital treatment times, intervention types or rates. Multivariate regression identified age, diabetes, female gender and multi-vessel disease as predictors of complications and death at 30 days. Conclusions: Migrants had longer pre-hospital delays and exhibited different cardiovascular risk profiles than Australian-born patients but received comparable treatment in the acute hospital setting. Higher rates of diabetes and multi-vessel coronary artery disease were seen among migrant patients, indicating a relatively higher risk population

Regional Ion Channel Gene Expression Heterogeneity and Ventricular Fibrillation Dynamics in Human Hearts

<div><p>Rationale</p><p>Structural differences between ventricular regions may not be the sole determinant of local ventricular fibrillation (VF) dynamics and molecular remodeling may play a role.</p><p>Objectives</p><p>To define regional ion channel expression in myopathic hearts compared to normal hearts, and correlate expression to regional VF dynamics.</p><p>Methods and Results</p><p>High throughput real-time RT-PCR was used to quantify the expression patterns of 84 ion-channel, calcium cycling, connexin and related gene transcripts from sites in the LV, septum, and RV in 8 patients undergoing transplantation. An additional eight non-diseased donor human hearts served as controls. To relate local ion channel expression change to VF dynamics localized VF mapping was performed on the explanted myopathic hearts right adjacent to sampled regions. Compared to non-diseased ventricles, significant differences (p<0.05) were identified in the expression of 23 genes in the myopathic LV and 32 genes in the myopathic RV. Within the myopathic hearts significant regional (LV <i>vs</i> septum <i>vs</i> RV) expression differences were observed for 13 subunits: Nav1.1, Cx43, Ca3.1, Cavα2δ2, Cavβ2, HCN2, Na/K ATPase-1, CASQ1, CASQ2, RYR2, Kir2.3, Kir3.4, SUR2 (p<0.05). In a subset of genes we demonstrated differences in protein expression between control and myopathic hearts, which were concordant with the mRNA expression profiles for these genes. Variability in the expression of Cx43, hERG, Na⁺/K⁺ ATPase ß1 and Kir2.1 correlated to variability in local VF dynamics (p<0.001). To better understand the contribution of multiple ion channel changes on VF frequency, simulations of a human myocyte model were conducted. These simulations demonstrated the complex nature by which VF dynamics are regulated when multi-channel changes are occurring simultaneously, compared to known linear relationships.</p><p>Conclusions</p><p>Ion channel expression profile in myopathic human hearts is significantly altered compared to normal hearts. Multi-channel ion changes influence VF dynamic in a complex manner not predicted by known single channel linear relationships.</p></div

Computer simulations.

<p>Effect of protein level changes on average frequency. Starting with the left (A) or right (B) ventricular myopathic ionic model, parameters were changed to match expression levels in the other ventricle as specified in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0082179#pone-0082179-t002" target="_blank">Table 2</a>. Increases in frequency are red while decreases are blue, with brighter colors indicating more change from control. Each ring represents a simulation with each quarter circle representing a parameter change. If the parameter was altered for the simulation, it is colored coded according to the resultant frequency change, otherwise it is left as grey. Frequencies range from 4.71–4.99 Hz with a baseline frequency of 4.83 Hz for the LV and 4.76 Hz for the RV.</p