Beyond Conventional Cardiac Resynchronisation Therapy: A Review of Electrophysiological Options in the Management of Chronic Heart Failure.

The incidence of heart failure (HF) continues to grow and burden our health care system. Electrophysiological aberrations are common amongst patients with heart failure and can contribute to worsening symptoms and prognosis. Targeting these abnormalities with cardiac and extra-cardiac device therapies and catheter ablation procedures augments cardiac function. Newer technologies aimed to improvement procedural outcomes, address known procedural limitations and target newer anatomical sites have been trialled recently. We review the role and evidence base for conventional cardiac resynchronisation therapy (CRT) and its optimisation, catheter ablation therapies for atrial arrhythmias, cardiac contractility and autonomic modulation therapies.

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.

Remote magnetic navigation compared to contemporary manual techniques for the catheter ablation of ventricular arrhythmias in structural heart disease.

BACKGROUND: There are limited data comparing remote magnetic navigation (RMN) to contemporary techniques of manual-guided ventricular arrhythmia (VA) catheter ablation. OBJECTIVES: We compared acute and long-term outcomes of VA ablation guided by either RMN or contemporary manual techniques in patients with structural heart disease. METHODS: From 2010-2019, 192 consecutive patients, with ischemic cardiomyopathy (ICM) or non-ischemic cardiomyopathy (NICM) underwent catheter ablation for sustained ventricular tachycardia (VT) or premature ventricular complexes (PVCs), using either RMN (n = 60) or manual (n = 132) guided techniques. Acute success and VA-free survival were compared. RESULTS: In ICM, acute procedural success was comparable between the 2 techniques (manual 43.5% vs. RMN 29%, P = 0.11), as was VA-free survival (manual 83% vs. RMN 74%, P = 0.88), and survival free from cardiac transplantation and all-cause mortality (manual 88% vs. RMN 87%, P = 0.47), both at 12-months after final ablation. In NICM, manual compared to RMN guided, had superior acute procedural success (manual 46% vs. RMN 19%, P = 0.003) and VA-free survival 12-months after final ablation (manual 79% vs. RMN 41%, P = 0.004), but comparable survival free from cardiac transplantation and all-cause mortality 12-months after final ablation (manual 95% vs. RMN 90%, P = 0.52). Procedural duration was shorter in both subgroups undergoing manual guided ablation, whereas fluoroscopy dose and complication rates were comparable. CONCLUSION: RMN provides similar outcomes to manual ablation in patients with ICM. In NICM however, acute success, and long-term VA-free survival was better with manual ablation. Prospective, multi-centre randomised trials comparing contemporary manual and RMN systems for VA catheter ablation are needed.

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.

Intraprocedure Type II Kounis Syndrome Secondary to Radioiodine Contrast During Coronary Angiography.

An 83-year-old man with a previous right coronary artery (RCA) stent presented to the emergency department with syncope, dynamic lateral ST depression, and a serum troponin of 6148 ng/L (< 17). Coronary angiography revealed a patent proximal RCA stent and significant left-sided disease. The procedure was complicated by inferior ST elevation, urticaria, hypotension, and acute proximal RCA occlusion. This required stenting, which acted as a scaffold to ameliorate subsequent vasospasm that responded to intracoronary glyceryl trinitrate. Serum tryptase postprocedure was markedly elevated at 81.7 µg/L (≤ 11.4) and subsequently normalized. This confirmed a rare presentation of intraprocedural type II Kounis syndrome likely due to radioiodine contrast.

Influence of BMI on inducible ventricular tachycardia and mortality in patients with myocardial infarction and left ventricular dysfunction: The obesity paradox.

BACKGROUND: There is little known about the influence of obesity on ventricular electrical remodelling after myocardial infarction. The aim of our study was to assess the relationship between body mass index (BMI) and the primary outcome of inducible-VT and the secondary outcome of all-cause mortality in consecutive patients who presented with ST elevation myocardial infarction (STEMI) and LV-dysfunction (LVEF ≤ 40%). METHODS AND RESULTS: Consecutive patients (n = 380) with STEMI and LV-dysfunction (LVEF ≤ 40%) underwent electrophysiological (EP) studies for risk-stratification. Inducible-VT ≥200 ms cycle-length (CL) with one to four extra-stimuli (ES) was considered abnormal. Patients were classified according their body mass index (BMI) to be normal (18.5-24.9), overweight (25-29.9) or obese (>30). The primary outcome of inducible-VT occurred in 42.7%, 21.5% and 21% of normal weight, overweight and obese patients respectively (p < 0.001). When adjusting for ejection-fraction, hypertension and triple-vessel-disease, normal BMI remained a significant predictor for inducible-VT. All-cause mortality was higher in patients with normal weight (12.8%) when compared to overweight (3.2%) and obese (3.8%) patients (p = 0.002) and was mainly driven by increased cardiac-death (6.8%, 1.9% and 1.9% in normal, overweight and obese patients respectively, p = 0.05). After adjusting for age, EF, and hypertension, normal BMI remained a significant predictor of mortality. CONCLUSION: In patients presenting with STEMI and LV-dysfunction, BMI appears to be a significant predictor of inducible-VT and all-cause mortality, with worse outcomes for those with normal weight, when compared to overweight or obese individuals. These findings are consistent with the obesity-paradox.

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.

Acoustic signal emission monitoring as a novel method to predict steam pops during radiofrequency ablation: preliminary observations.

UNLABELLED: Steam pop is an explosive rupture of cardiac tissue caused by tissue overheating above 100 °C, resulting in steam formation, predisposing to serious complications associated with radiofrequency (RF) ablations. However, there are currently no reliable techniques to predict the occurrence of steam pops. We propose the utility of acoustic signals emitted during RF ablation as a novel method to predict steam pop formation and potentially prevent serious complications. METHODS: Radiofrequency generator parameters (power, impedance, and temperature) were temporally recorded during ablations performed in an in vitro bovine myocardial model. The acoustic system consisted of HTI-96-min hydrophone, microphone preamplifier, and sound card connected to a laptop computer. The hydrophone has the frequency range of 2 Hz to 30 kHz and nominal sensitivity in the range -240 to -165 dB. The sound was sampled at 96 kHz with 24-bit resolution. Output signal from the hydrophone was fed into the camera audio input to synchronize the video stream. An automated system was developed for the detection and analysis of acoustic events. RESULTS: Nine steam pops were observed. Three distinct sounds were identified as warning signals, each indicating rapid steam formation and its release from tissue. These sounds had a broad frequency range up to 6 kHz with several spectral peaks around 2-3 kHz. Subjectively, these warning signals were perceived as separate loud clicks, a quick succession of clicks, or continuous squeaking noise. Characteristic acoustic signals were identified preceding 80% of pops occurrence. Six cardiologists were able to identify 65% of acoustic signals accurately preceding the pop. An automated system identified the characteristic warning signals in 85% of cases. The mean time from the first acoustic signal to pop occurrence was 46 ± 20 seconds. The automated system had 72.7% sensitivity and 88.9% specificity for predicting pops. CONCLUSIONS: Easily identifiable characteristic acoustic emissions predictably occur before imminent steam popping during RF ablations. Such acoustic emissions can be carefully monitored during an ablation and may be useful to prevent serious complications during RF delivery.

Ventricular tachyarrhythmia recurrence in primary versus secondary implantable cardioverter-defibrillator patients and role of electrophysiology study.

PURPOSE: In recent years, there has been a shift away from performing electrophysiologic study (EPS) to guide implantable cardioverter-defibrillator (ICD) implantation with a reliance on left ventricular ejection fraction (LVEF) alone. METHODS: ICD patients were prospectively recruited from the multicentre COMFORT (Concept of Optimal Management of ventricular Fibrillation Or Very fast ventricular Tachycardia) trial. Primary prevention ICD patients (n = 260, groups 1 and 2) were compared to secondary prevention ICD patients (n = 210, group 3). Primary prevention ICDs were implanted in patients with ischemic cardiomyopathy based on LVEF ≤ 40 % and inducible ventricular tachycardia (VT) at EPS (n = 123, group 1) or impaired LVEF alone (LVEF ≤ 30 % or LVEF ≤ 35 % with NYHA class II or III; n = 137, group 2). EPS was performed in 61 % of secondary prevention ICD patients (n = 129). Patients were followed up for >12 months with a primary endpoint of spontaneous VT/ventricular fibrillation (VF). RESULTS: A significantly higher rate of spontaneous VT/VF occurred in secondary versus primary prevention ICD patients (P < 0.001) and in EPS-guided versus LVEF-guided primary prevention ICD patients (P = 0.029). At 2 years, the proportion of patients with ≥1 VT/VF episode was 24.6 ± 4.2 %, 19.9 ± 4.6 % and 37.1 ± 3.9 % for groups 1, 2 and 3, respectively. In the secondary prevention, patients who underwent EPS, VT/VF occurred in 44.4 ± 5.9 % and 14.1 ± 6.6 % with a positive versus negative result, respectively (P = 0.02). CONCLUSIONS: Secondary prevention ICD patients have more spontaneous VT/VF than primary prevention ICD patients. Secondary and primary prevention ICD patients with inducible VT at EPS have more VT/VF than patients without inducible VT or impaired LVEF alone.

Electrogram-gated radiofrequency ablations with duty cycle power delivery negate effects of ablation catheter motion.

BACKGROUND: Cardiac and respiratory movements cause catheter instability. Lateral catheter sliding over target endocardial surface can lead to poor tissue contact and unpredictable lesion formation. We describe a novel method of overcoming the effects of lateral catheter sliding movements using an electrogram-gated pulsed power ablation. METHODS AND RESULTS: All ablations were performed on a thermochromic gel myocardial phantom. Ablation settings were randomized to conventional (nongated) 30 W versus electrogram-gated at 20% duty cycle (30 W average power) at 0-, 3-, 6-, and 9-mm lateral sliding distances. Forty-eight radiofrequency ablations were performed. Deeper lesions were created in electrogram-gated versus conventional ablations at 3 mm (4.36±0.08 versus 4.05±0.17 mm; P=0.009), 6 mm (4.39±0.10 versus 3.44±0.15 mm; P<0.001), and 9 mm (4.41±0.06 versus 2.94±0.16 mm; P<<0.001) sliding distances. Electrogram-gated ablations created consistent lesions at a quicker rate of growth in depth when compared with conventional ablations (P<0.001). CONCLUSIONS: (1) Lesion depth decreases and length increases in conventional ablations with greater degrees of lateral catheter movements; (2) electrogram-gated pulsed radiofrequency delivery negated the effects from lateral catheter movement by creating consistently deeper lesions irrespective of the degree of catheter movement; and (3) target lesion depths were reached significantly faster in electrogram-gated than in conventional ablations.

Right ventricular dysfunction predisposes to inducible ventricular tachycardia at electrophysiology studies in patients with acute ST-segment-elevation myocardial infarction and reduced left ventricular ejection fraction.

BACKGROUND: Inducible ventricular tachycardia (VT) is a strong predictor of spontaneous ventricular tachyarrhythmia following ST-segment-elevation myocardial infarction. Reduced left ventricular ejection fraction (EF) predisposes patients to inducible VT after ST-segment-elevation myocardial infarction. However, the role of right ventricular (RV) dysfunction in predisposing to inducible VT has not been described previously. METHODS AND RESULTS: Consecutive patients with ST-segment-elevation myocardial infarction treated with primary percutaneous coronary intervention underwent predischarge radionuclide gated heart pool scan to assess ventricular EF. The study cohort included patients with reduced left ventricular EF (left ventricular EF ≤40%) who underwent electrophysiology study (n=220) in an attempt to induce VT. We defined RV dysfunction as RVEF ≤35%. The end point was sustained monomorphic VT (cycle length ≥200 ms). This was considered a positive study. No inducible arrhythmia, ventricular fibrillation, or flutter (cycle length <200 ms) was considered a negative study. Infarct region, infarct-related artery, male sex, and RVEF ≤35% were univariable predictors of positive test. After multivariable analysis, RVEF ≤35% had the strongest association as an independent predictor of inducible VT at electrophysiology study (P<0.001; odds ratio, 5.8; 95% confidence interval, 3.005-11.262). CONCLUSIONS: RV dysfunction (RVEF ≤35%) predisposed to inducible VT at electrophysiology study in patients with impaired left ventricular EF (≤40%) after acute ST-segment-elevation myocardial infarction treated with primary percutaneous coronary intervention.

Evaluation of lesion and thermodynamic characteristics of Symplicity and EnligHTN renal denervation systems in a phantom renal artery model.

AIMS: Radiofrequency renal artery denervation has been used effectively to treat resistant hypertension. However, comparison of lesion and thermodynamic characteristics for different systems has not been previously described. We aimed to assess spatiotemporal lesion growth and ablation characteristics of Symplicity and EnligHTN systems. METHODS AND RESULTS: A total of 39 ablations were performed in a phantom renal artery model using Symplicity (n=17) and EnligHTN (n=22) systems. The phantom model consisted of a hollowed gel block surrounding a thermochromic liquid crystal (TLC) film, exhibiting temperature sensitivity of 50-78°C. Flow was simulated using 37°C normal saline with impedance equal to blood. Radiofrequency ablations with each system were delivered with direct electrode tip contact to the TLC. Lesion size was interpreted from the TLC as the maximum dimensions of the 51°C isotherm. Mean lesion depth was 3.82 mm±0.04 versus 3.44 mm±0.03 (p<0.001) for Symplicity and EnligHTN, respectively. Mean width was 7.17 mm±0.08 versus 6.23 mm±0.07 (p<0.001), respectively. With EnligHTN, steady state temperature was achieved 20 sec earlier, and was 15°C higher than Symplicity. CONCLUSIONS: In this phantom model, Symplicity formed larger lesions compared to EnligHTN with lower catheter-tip temperature. The clinical significance of our findings needs to be explored further.

What is the optimal left ventricular ejection fraction cut-off for risk stratification for primary prevention of sudden cardiac death early after myocardial infarction?

AIMS: The optimal left ventricular ejection fraction (LVEF) to select patients early post myocardial infarction (MI) for risk stratification for prevention of sudden cardiac death (SCD) in the era of primary percutaneous coronary intervention (PPCI) is unknown. METHODS AND RESULTS: Consecutive patients (n = 1722) treated with PPCI for ST-elevation MI underwent early (median 4 days) LVEF assessment. An electrophysiological study (EPS) was performed if LVEF ≤40% and a prophylactic implantable-cardioverter defibrillator (ICD) implanted for a positive [inducible monomorphic ventricular tachycardia (VT)], but not a negative, result. According to an early LVEF, a primary endpoint of inducible VT at EPS and a secondary endpoint of death or arrhythmia (SCD, resuscitated cardiac arrest or ECG-documented VT/ventricular fibrillation) were determined. The proportion of patients with early LVEF >40, 36-40, 31-35, and ≤30% were 75% (n = 1286), 7% (n = 128), 8% (n = 136), and 10% (n = 172), respectively. Inducible VT occurred in 22, 25, and 40% of patients with LVEF 36-40, 31-35, and ≤30%, respectively (P = 0.014). Three-year death or arrhythmia occurred in 6.6 ± 0.8, 8.1 ± 2.6, 18.0 ± 3.4, and 37.4 ± 3.9% of patients with LVEF >40, 36-40, 31-35, and ≤30%, respectively (overall P<0.001; LVEF 36-40% vs. LVEF > 40% P = 0.265). The number of EPS-positive patients implanted with an ICD to treat one or more arrhythmic event (95% confidence interval) was 18.3 ± 2.4, 11.5 ± 3.0, and 4.2 ± 5.6 if LVEF is 36-40, 31-35, and ≤30%, respectively. CONCLUSION: A cut-off LVEF of ≤40% selects patients with a high incidence of inducible VT post-PPCI. Patients with LVEF ≤35% and inducible VT appear to derive a greater benefit from prophylactic ICD implantation due to their higher risk of death or arrhythmia.

Significance of repeat programmed ventricular stimulation at electrophysiology study for arrhythmia prediction after acute myocardial infarction.

BACKGROUND: The prognostic significance of a second programmed ventricular stimulation (PVS) at electrophysiology study (EPS), when the first PVS is negative for inducible ventricular tachycardia (VT), in patients following myocardial infarction (MI) is unknown. METHODS: Consecutive ST-elevation MI patients with left ventricular ejection fraction ≤ 40% following revascularization underwent early EPS. An implantable cardioverter defibrillator (ICD) was implanted for a positive (inducible monomorphic VT) but not a negative (no arrhythmia or inducible ventricular fibrillation [VF]/flutter) EPS. The combined primary end point of death or arrhythmia (sudden death, resuscitated cardiac arrest, and spontaneous VT/VF) was assessed in EPS-positive patients grouped according to if VT was induced on the first PVS application, or the second PVS application, when the first was negative. RESULTS: EPS performed a median 8 days post-MI in 290 patients was negative in 70% (n = 203) and positive in 30% (n = 87). In patients with a positive EPS, VT was induced on the first PVS in 67% (n = 58) and the second PVS, after the first was negative, in 33% (n = 29). Predischarge ICD was implanted in 79 of 87 patients with a positive EPS. Three-year primary end point occurred in 20.9 ± 5.6% and 38.3 ± 9.7% of patients with VT induced by the first and second PVS, respectively (P = 0.042) and in 6.3 ± 1.9% of electrophysiology-negative patients (P < 0.001). CONCLUSIONS: In patients with post-MI left ventricular dysfunction, VT can be induced in a significant proportion with a second PVS when negative on the first. These patients have a similar higher risk of death or arrhythmia compared to patients with VT induced on the first PVS.

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

AIMS: Current 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. METHODS AND RESULTS: 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. CONCLUSION: 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.

Long-term arrhythmia-free survival in patients with severe left ventricular dysfunction and no inducible ventricular tachycardia after myocardial infarction.

BACKGROUND: A negative electrophysiology study (EPS) may delineate a subgroup of patients with severely impaired left ventricular ejection fraction (LVEF) whose care can be safely managed long-term without an implantable cardioverter-defibrillator. METHODS AND RESULTS: Consecutive patients treated with primary percutaneous coronary intervention for ST-segment-elevation myocardial infarction underwent early (median 4 days) LVEF assessment. Patients with LVEF ≤40% underwent EPS. A prophylactic implantable cardioverter-defibrillator was implanted for a positive (inducible monomorphic ventricular tachycardia) but not a negative (no inducible ventricular tachycardia or inducible ventricular fibrillation/flutter) EPS result. Patients who would have become eligible for a late primary prevention implantable cardioverter-defibrillator with LVEF ≤30% or ≤35% with New York Heart Association class II/III heart failure were included and analyzed according to EPS result. Patients with LVEF >40%, ineligible for EPS, were followed up as control subjects (n=1286). The primary end point was survival free of death or arrhythmia (resuscitated cardiac arrest or sustained ventricular tachycardia/ventricular fibrillation). EPS performed in 128 patients with LVEF ≤30% or with LVEF ≤35% and heart failure was negative in 63% (n=80) and positive in 37% (n=48). Implantable-cardioverter defibrillators were implanted in <0.1%, 4%, and 90% of control, EPS-negative, and EPS-positive patients, respectively. The distribution of time to death or arrhythmia was comparable in control patients and EPS-negative patients with LVEF ≤30% or with LVEF ≤35% and heart failure (P=0.738), who both differed significantly from EPS-positive patients (P<0.001). At 3 years, 91.8 ± 3.2%, 93.4 ± 1.0%, and 62.7 ± 7.5% of control, EPS-negative, and EPS-positive patients were free of death or arrhythmia, respectively. CONCLUSIONS: Revascularized patients with ST-segment-elevation myocardial infarction with severely impaired left ventricular function but no inducible ventricular tachycardia have a favorable long-term prognosis without the protection of an implantable cardioverter-defibrillator.

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, Cavα2δ2, Cavß2, 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.