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Key words: Cardioneuroablation, Atrioventricular block, Syncope, Arrhythmia According to clinical guidelines a symptomatic atrioventricular block (AV block) is treated with a pacemaker. For young individuals such a therapy can be difficult due to possible long term complications such as infections, lead disruptions and pacemaker induced cardiomyopathy. We describe a twenty year old man with recurrent syncopes due to intermittent parasympathetic caused AV block of grade 2. The patient underwent cardioneuroablation where parasympathetic ganglia in the right atrium were ablated. After the procedure the PR interval normalized. This procedure has never been performed in Iceland before and there is a limited amount of case reports in the literature.

Empirical approaches to targeting the ventricular tachycardia (VT) substrate include mapping of late potentials, local abnormal electrogram, pace-mapping and homogenisation of the abnormal signals. These approaches do not try to differentiate between the passive or active role of local signals as the critical components of the VT circuit. By not considering the functional components, these approaches often view the substrate as a fixed anatomical barrier. Strategies to improve the success of VT ablation need to include the identification of critical functional substrate. Decrement-evoked potential (DeEP) mapping has been developed to elucidate this using an extra-stimulus added to a pacing drive train. With knowledge translation in mind, the authors detail the evolution of the DeEP concept by way of a study of simultaneous panoramic endocardial mapping in VT ablation; an in silico modelling study to demonstrate the factors influencing DeEPs; a multicentre VT ablation validation study; a practical approach to DeEP mapping; the potential utility of DeEPs to identify arrhythmogenic atrial substrate; and, finally, other functional mapping strategies.

Objectives The study sought to localize focal sources (FS) during atrial fibrillation (AF) using periodic component analysis (PiCA) and QS unipolar electrogram (EGM) morphology based on the assumption that periodic activation with centrifugal propagation is inherent to a FS. Background The localization of FS maintaining AF remains challenging, due to limitations in conventional time-frequency domain analysis. This is relevant to identifying targets for AF substrate ablation. Methods In 41 patients (age 56 ± 9 years, 76% persistent AF), bipolar EGMs were recorded in the left atrium (LA) during AF with a roving 20-pole catheter. Bipolar EGMs with periodicity were determined using PiCA. FS were defined as periodic sites with predominantly QS unipolar EGM morphology. Results For each patient, 456 ± 109 bipolar EGMs were recorded, of which 261 ± 15 (60%) demonstrated periodicity. FS were identified in 63% of patients (pulmonary vein [PV] 1.5 ± 1.5; extra-PV 2.6 ± 2.3). After PV antral ablation and follow-up of 14 ± 9 months, 37% of patients had symptomatic AF recurrence. Mean global LA periodicity cycle length was shorter in patients with AF recurrence compared to those without (143 ± 20 ms vs. 154 ± 9 ms; p = 0.02). Among 12 (29%) patients with FS exclusively in the PV, only 1 (8%) had AF recurrence. AF recurrence was significantly higher (50%; p = 0.01) in 14 (34%) patients with extra-PV FS. Conclusions Our novel hierarchical analysis schema, incorporating PiCA and unipolar EGM morphology, detected a small number of FS in patients with predominantly persistent AF. FS in the PV was associated with successful PV antral ablation. Further prospective studies are required to determine whether these FS maintain AF and represent ablation targets.

Background— Substrate-based mapping for ventricular tachycardia (VT) ablation is hampered by its inability to determine critical sites of the VT circuit. We hypothesized that those potentials, which delay with a decremental extrastimulus (decrement evoked potentials or DEEPs), are more likely to colocalize with the diastolic pathways of VT circuits. Methods and Results— DEEPs were identified in intraoperative left ventricular maps from 6 patients with ischemic cardiomyopathy (total 9 VTs) and were compared with late potential (LP) and activation maps of the diastolic pathway for each VT. Mathematical modeling was also used to further validate and elucidate the mechanisms of DEEP mapping. All patients demonstrated regions of DEEPs and LPs. The mean endocardial surface area of these potentials was 18±4% and 21±6%, respectively ( P =0.13). The mean sensitivity for identifying the diastolic pathway in VT was 50±23% for DEEPs and 36±32% for LPs ( P =0.31). The mean specificity was 43±23% versus 20±8% for DEEP and LP mapping, respectively ( P =0.031). The electrograms that displayed the greatest decrement in each case had a sensitivity and specificity for the VT isthmus of 29±10% and 95±1%, respectively. Mathematical modeling studies recapitulated DEEPs at the VT isthmus and demonstrated their role in VT initiation with a critical degree of decrement. Conclusions— In this preliminary study, DEEP mapping was more specific than LP mapping for identifying the critical targets of VT ablation. The mechanism of DEEPs relates to conduction velocity restitution magnified by zigzag conduction within scar channels.

OBJECTIVES: The authors conducted a multicenter study of decrement-evoked potential (DEEP)-based functional ventricular tachycardia (VT) substrate modification to evaluate if such a mechanistic and physiological strategy is feasible and efficient in clinical practice and provides reduction in the VT burden.BACKGROUND: Only a fraction of the myocardium targeted in current VT substrate modification procedures is involved in the initiation and perpetuation of VT. The physiological basis of the DEEP strategy for identification of areas of initiation and maintenance of VT was recently established.METHODS: We included 20 consecutive patients with ischemic cardiomyopathy. During substrate mapping, fractionated and late potentials (LPs) were tagged, and an extra stimulus was performed to determine which LPs displayed decrement (DEEPs). All patients underwent DEEP-focused ablation: elimination of DEEP + further radiofrequency (RF) if VT was still inducible. Patients were followed during 6 months.RESULTS: Patients were predominantly male (95%), and their mean age was 64.6 ± 17.1 years. Mean left ventricular ejection fraction was 33.4 ± 11.4%. Mean ablation time was 30.6 ± 20.4 min. Specificity of DEEPs to detect the isthmus of VT was better than that of LPs (0.97 [95% confidence interval [CI]: 0.95 to 0.98] vs. 0.82 [95% CI: 0.73 to 0.89]), without significant differences in terms of sensitivity (0.61 [95% CI: 0.52 to 0.69] vs. 0.60 [95% CI: 0.44 to 0.74], respectively). Fifteen of 20 (75%) patients were free of any VT after DEEP-RF at 6 months of follow-up and there was a strong reduction in VT burden compared to 6 months pre-ablation.CONCLUSIONS: In a multicenter prospective study, DEEP substrate mapping identified the functional substrate critical to the VT circuit with high specificity. DEEP-guided VT ablation, by its physiological nature, may enable greater access to focused ablation therapy for patients requiring VT treatment.

Background— The therapeutic potential of renal denervation (RDN) for arrhythmias has not been fully explored. Detailed mechanistic evaluation is in order. The objective of the present study was to determine the antiarrhythmic potential of RDN in a postinfarct animal model and to determine whether any benefits relate to RDN-induced reduction of sympathetic effectors on the myocardium. Methods and Results— Pigs implanted with single-chamber implantable cardioverter defibrillators to record ventricular arrhythmias (VAs) were subjected to percutaneous coronary occlusion to induce myocardial infarction. Two weeks later, a sham or real RDN treatment was performed bilaterally using the St Jude EnligHTN basket catheter. Parameters of ventricular remodeling and modulation of cardio–renal sympathetic axis were monitored for 3 weeks after myocardial infarction. Histological analysis of renal arteries yielded a mean neurofilament score of healthy nerves that was significantly lower in the real RDN group than in sham controls; damaged nerves were found only in the real RDN group. There was a 100% reduction in the rate of spontaneous VAs after real RDN and a 75% increase in the rate of spontaneous VAs after sham RDN ( P =0.03). In the infarcted myocardium, presence of sympathetic nerves and tissue abundance of neuropeptide-Y, an indicator of sympathetic nerve activities, were significantly lower in the RDN group. Peak and mean sinus tachycardia rates were significantly reduced after RDN. Conclusions— RDN in the infarcted pig model leads to reduction of postinfarction VAs and myocardial sympathetic effectors. This may form the basis for a potential therapeutic role of RDN in postinfarct VAs.

Arrhythmias have been treated for a long time with drugs that mainly target the ionic pumps and channels. These anti-arrhythmic regimens per se introduce new arrhythmias, which can be detrimental to patients. Advances in development of novel pharmacology without introduction of iatrogenic arrhythmias are thus favorable for an effective treatment of arrhythmias. Electrophysiological stability of the heart has been shown to be closely associated with cardiac metabolism. The present effective anti-arrhythmic drugs such as beta-blockers and amiodarone have profound beneficial effects in regulating myocardial metabolism. Aiming at decreasing production of toxic metabolites or preventing accumulation of arrhythmogenic lipids perhaps is a good strategy to effectively control arrhythmias. Therefore, a better understanding of the pro-arrhythmic profiles of cardiac metabolites helps to explore a new generation of metabolically oriented anti-arrhythmic medications. In this review, we present several lipid metabolites and summarize their arrhythmogenic characteristics.

Importance Quality of life is not a standard primary outcome in ablation trials, even though symptoms drive the indication. Objective To assess quality of life with catheter ablation vs antiarrhythmic medication at 12 months in patients with atrial fibrillation. Design, Setting, and Participants Randomized clinical trial at 4 university hospitals in Sweden and 1 in Finland of 155 patients aged 30-70 years with more than 6 months of atrial fibrillation and treatment failure with 1 antiarrhythmic drug or β-blocker, with 4-year follow-up. Study dates were July 2008–September 2017. Major exclusions were ejection fraction 60 mm, ventricular pacing dependency, and previous ablation. Interventions Pulmonary vein isolation ablation (n = 79) or previously untested antiarrhythmic drugs (n = 76). Main Outcomes and Measures Primary outcome was the General Health subscale score (Medical Outcomes Study 36-Item Short-Form Health Survey) at baseline and 12 months, assessed unblinded (range, 0 [worst] to 100 [best]). There were 26 secondary outcomes, including atrial fibrillation burden (% of time) from baseline to 12 months, measured by implantable cardiac monitors. The first 3 months were excluded from rhythm analysis. Results Among 155 randomized patients (mean age, 56.1 years; 22.6% women), 97% completed the trial. Of 79 patients randomized to receive ablation, 75 underwent ablation, including 2 who crossed over to medication and 14 who underwent repeated ablation procedures. Of 76 patients randomized to receive antiarrhythmic medication, 74 received it, including 8 who crossed over to ablation and 43 for whom the first drug used failed. General Health score increased from 61.8 to 73.9 points in the ablation group vs 62.7 to 65.4 points in the medication group (between-group difference, 8.9 points; 95% CI, 3.1-14.7;P = .003). Of 26 secondary end points, 5 were analyzed; 2 were null and 2 were statistically significant, including decrease in atrial fibrillation burden (from 24.9% to 5.5% in the ablation group vs 23.3% to 11.5% in the medication group; difference –6.8% [95% CI, –12.9% to –0.7%];P = .03). Of the Health Survey subscales, 5 of 7 improved significantly. Most common adverse events were urosepsis (5.1%) in the ablation group and atrial tachycardia (3.9%) in the medication group. Conclusions and Relevance Among patients with symptomatic atrial fibrillation despite use of antiarrhythmic medication, the improvement in quality of life at 12 months was greater for those treated with catheter ablation compared with antiarrhythmic medication. Although the study was limited by absence of blinding, catheter ablation may offer an advantage for quality of life. Trial Registration clinicaltrialsregister.eu Identifier:2008-001384-11

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.

AIMS: Left ventricular (LV) epicardial pacing (LVEpiP) in human myopathic hearts does not decrease global epicardial activation delay compared with right ventricular (RV) endocardial pacing (RVEndoP); however, the effect on transmural activation delay has not been evaluated. To characterize the transmural electrical activation delay in human myopathic hearts during RVEndoP and LVEpiP compared with global epicardial activation delay. METHODS AND RESULTS: Explanted hearts from seven patients (5 male, 46 ± 10 years) undergoing cardiac transplantation were Langendorff-perfused and mapped using an epicardial sock electrode array (112 electrodes) and 25 transmural plunge needles (four electrodes, 2 mm spacing), for a total of 100 unipolar transmural electrodes. Electrograms were recorded during LVEpiP and RVEndoP, and epicardial (sock) and transmural (needle) activation times, along with patterns of activation, were compared. There was no difference between the global epicardial activation times (LVEpiP 147 ± 8 ms vs. RVEndoP 156 ± 17 ms, P = 0.46). The mean LV transmural activation time during LVEpiP was significantly shorter than that during RVEndoP (125 ± 44 vs. 172 ± 43 ms, P

A 36-year-old woman presented with paroxysmal palpitations and shortness of breath to the emergency department. She was known to have transposition of the great arteries and had undergone the Mustard operation, in addition to having a pacemaker implanted. The electrocardiogram at the time of …

Atrial fibrillation (AF) is the most common form of arrhythmia in humans and is associated with substantial morbidity and mortality. Obesity and diabetes have been linked to myocardial lipotoxicity - a condition where the heart accumulates and produces toxic lipid species. We hypothesized that obesity and diabetes were involved in the pathophysiology of AF by means of promoting a lipotoxic phenotype in atrial muscle, and that AF predicts mortality in cardiac care patients.Our study consists of two parts. The first part is a registry study based on prospective data obtained through the Register of Information and Knowledge about Swedish Heart Intensive Care Admissions (RIKS-HIA) from hospitals in western Sweden. All consecutive patients between 2006 and 2011 admitted to coronary care unit (CCU) with sinus rhythm (SR) or AF were included in the analysis. Multivariate logistic regression and Cox proportional-hazards regression were used to test whether diabetes and obesity were independent predictors of AF at admission to CCU and whether AF was associated with increased one-year mortality. In the second part we obtained atrial biopsies from 54 patients undergoing cardiac surgery and performed lipidomic analysis for a detailed qualitative and quantitative analysis of lipid species including triglycerides (TAG), ceramides (CER), phosphatidylcholine (PC), lysophosphatidylcholine (LPC), phosphatidylethanolamine (PE), sphyngomyelins (SM), free cholesterol (FC), cholesterol esters (CEs) and diacylglycerols (DAGs).Between 2006 and 2011, 35232 patients were admitted to CCUs in western Sweden, mostly due to ischemic heart disease, heart failure, arrhythmia, syncope and chest pain. The mean age was 66years and 58.7% were male. There was a high prevalence of obesity (20.3%) and diabetes (16.8%). Obesity (OR 1.35, 95% CI 1.17-1.56, P0.001) and severe obesity (1.6, 95% CI 1.29-1.99, P0.001) were independent predictors of AF but diabetes was not (OR=0.92, 95% CI=0.82-1.04). AF increased one-year mortality (HR 1.32, 95% CI 1.16-1.50, P0.001). Lipidomic analysis revealed that atrial TAG content was substantially lower in the AF patients (P0.05). No quantitative difference was found in the content of CER, PC, LPC, PE, SM, FC, CE and DAG, between the patients who had AF or sinus rhythm at admission to the CCU. AF patients had greater proportion of polyunsaturated DAG (P0.05) while no difference was found in saturated DAG.Obesity but not diabetes is an independent predictor of AF and AF is associated with increased one-year mortality in this CCU population. AF is associated with quantitative and qualitative alterations in atrial lipid content but not with lipotoxicity.

In humans, the existence of rotors or reentrant sources maintaining atrial fibrillation (AF) and the underlying electroanatomic substrate has not been well defined.Our aim was to determine the prevalence of localized rotational activation (RotA) in the left atrium (LA) during human AF and whether complex fractionated atrial electrograms (CFAEs) or low-voltage areas colocalize with RotA sites.We prospectively studied 32 patients (mean age 57 ± 8 years; 88% with persistent AF) undergoing AF catheter ablation. Bipolar electrograms were recorded for 2.5 seconds during AF using a roving 20-pole circular catheter in the LA. RotA was defined as sequential temporal activation of bipoles around the circular catheter. Bipolar electrogram fractionation index and bipolar voltage were used to define CFAEs and low-voltage areas, respectively.In 21 (66%) patients, 47 RotA sites were identified. Few (9%) lasted 2.5 seconds (cycle length 183 ± 6 ms), while the majority (91%) were nonsustained (duration 610 ± 288 ms; cycle length 149 ± 11 ms). RotA was most common in the pulmonary vein antrum (71%) and posterior LA (25%). CFAEs were recorded from 18% ± 12% of LA area, and most (92% ± 7%) were not associated with RotA sites. However, 85% of RotA sites contained CFAEs. Very low voltage (0.1 mV) areas comprised 12% ± 10% of LA area and were present in 23% of RotA sites.In patients with predominantly persistent AF, localized RotA is commonly present but tends to be transient (1 second). Although most CFAEs do not colocalize with RotA sites, the high prevalence of CFAEs and very low voltages within RotA sites may indicate slow conduction in diseased myocardium necessary for their maintenance.

Background: Sudden death due to malignant ventricular arrhythmias is the most important cause of death in acute myocardial infarction. Improved knowledge about the pathophysiology underlying these arrhythmias is essential in the search for new anti-arrhythmic strategies. Lysophosphatidylcholine (LPC), a hydrolysis product of (membrane) phospholipid degradation, is one of the most potent pro-arrhythmic substances that accumulate in the human heart during myocardial ischemia. The aim of this study was to set up and validate an in vitro experimental system for studies on the effects of LPC on electrophysiological parameters in beating cardiomyocytes. Methods and Results: Spontaneously beating HL-1 cardiomyocytes were cultured on multielectrode array microchips for three days for the recording of electrical activities in the form of field potentials (FP). FPs were recorded at baseline and after addition of 2, 4, 8, 12, 16, 20, and 24 µM of LPC to the cell medium (n=9). We found that LPC could induce rapid effects on electrical parameters in the HL-1 cells. The overall half-maximal effective concentration (EC50) of LPC was around 12 µM. The beating rate and peak-peak amplitude of FP thus decreased at concentrations ≥ 12 µM and were inversely proportional to increased LPC concentration. The duration of FP was significantly prolonged with LPC above 12 µM and was concentration-dependent. LPC delayed signal propagation, an effect which was mimicked by blocking gap junctions with heptanol and attenuated by pre-treatment with isoprenaline and atropine. Finally, asynchronous activity was induced by LPC at >12 µM. Conclusions: LPC induced prompt and pronounced electrophysiological alterations that may underlie its observed pro-arrhythmic properties. Our in vitro model with HL-1 cells and microelectrode array system may be a useful tool for preclinical studies of electrophysiological effects of various pathophysiological concepts.

Aims Severe sustained bradycardia may cause acute and possibly chronic congestive heart failure (CHF). The aim of this study was to investigate acute and chronic effects of complete heart block (CHB) on cardiac function, morphology, and creatine (Cr) metabolism. Methods and results CHB was induced in male Sprague–Dawley rats (250 g, n ¼ 11) by means of electrocautery applied to the region of AV node and were compared with controls (n ¼ 15). The rats were investigated at 1, 3, and 12 weeks after CHB induction with transthoracic echocardiography. Invasive haemodynamic assessment of left and right ventricular pressures was performed at 12 weeks. After the sacrifice, the hearts were freeze-clamped for analysis of myocardial Cr, and high energy phosphometabolites. The efficacy of operative procedure was 54%. The peri-operative mortality rate was 20%. Heart rate (HR) decreased by 50% (P , 0.01) while stroke volume (SV) increased 2.5 times (P , 0.01) in the CHB rats. Cardiac index remained unchanged. The rats with CHB grew normally and were in no apparent distress. Filling pressures in left and right ventricles were normal. The CHB rats developed marked cardiomegaly with biventricular dilatation and eccentric left ventricular hypertrophy (P , 0.01). There was no change in the myocardial content of Cr and high energy phosphometabolites. Conclusion Rats with CHB are compensating for reduction in HR with increased SV without haemodynamic and biochemical characteristics of CHF. This model may be useful to study the effects of CHB and bradycardia on myocardial structure, function, electrophysiology, and metabolism as well as for studies of cell therapy for reparation of AV conductance.

s S43 therapy may need to be considered (percutaneous VSD closure and heart transplant) especially in patients with posterior VSD. 086 THE EFFECT OF SHORTVERSUS LONG-ACTING ANTIHYPERTENSIVES ON BLOOD PRESSURE, NIGHT-DAY RATIO AND OTHER PARAMETERS OF BLOOD PRESSURE VARIABILITY J Gorgui, SS Daskalopoulou

In the current issue of HeartRhythm, Chinitz et al present a novel scoring system (atrial fibrillation ablation [AFA] score) for evaluating the quality and success of catheter ablation for the treatment of paroxysmal atrial fibrillation (AF). We have paraphrased the words attributed to Sir Winston Churchill to give context to the transience of the wins and losses perceived in the greater battle against the formidable opponent of AF. We did this in order to shed light, and to pause and think of the direction AF ablation— the most prolific business in interventional electrophysiology —is taking. In their article, Chinitz et al underline the fact that a scoring system that incorporates quality and success has not been available for AF ablation and that the current use of AF recurrence as an outcome measure has limitations. The AFA score takes into account disparate factors such as lesion delivery, complications, and outcomes in order to evaluate the results and quality of AF ablation and allows for comparison of different techniques. This is achieved by incorporating 6 procedural features, half of which estimate efficacy and the other three reflect the relative acute safety of the procedure. A very strong emphasis is made on the total number of procedures performed, as seen in the relatively high score achieved by radiofrequency ablation in their article compared with emerging balloon techniques (cryo and laser), even though both redo and reconduction rates are quite similar among all methods, as seen in their Table 1. Although one would consider the novelty of this score may lie (if validated against meaningful outcomes) in its value in showing differences among manufacturers, operators, techniques, and institutions, the devil is always in the details. Like all creative concepts, this concept paper raises more questions than provides solutions to the problem at hand. What would this difference in score mean to the patient we hope to care for? The user of this score will not take into account the very premise for performing the procedure, that is, symptom relief. The score will only allow for comparison of nonpharmacologic treatment strategies that strictly target the pulmonary veins and does not permit comparison of AF

The right atrial appendage can be the origin of focal atrial tachycardias. Their ablation can be challenging owing to the complexity of the appendage anatomy. To our knowledge, we describe the first successful solid tip cryoablation of a focal tachycardia within the right atrial appendage in a patient presenting with tachycardia-induced cardiomyopathy.