Circulation: Arrhythmia and Electrophysiology March 2019 Issue

Circulation: Arrhythmia and Electrophysiology On the Beat

Dr Paul Wang: Welcome to the monthly podcast "On the Beat" for Circulation: Arrhythmia, and Electrophysiology. I'm Dr Paul Wang, Editor-in Chief, with some of the key highlights from this month's issue.

In our first manuscript, Marie Bayer Elming and associates, examined whether the right ventricular ejection fraction can identify patients with non-ischemic systolic heart failure, more likely to benefit from ICD implantation. The Danish study, to assess the efficacy of ICDs in patients with non-ischemic systolic heart failure, on mortality, the Danish study, randomized patients with non-ischemic systolic heart failure to ICD our control. In 239 patients with interpretable cardiovascular magnetic resonance images, the right ventricular volume and ejection fraction was measured. Right ventricular ejection fraction was an independent predictor of all-cause mortality, with a hazard ration 1.34 per 10% absolute decrease in our right ventricular ejection fraction. P=0.02. There is statistically significant interaction between right ventricular ejection fraction and the effect of ICD implantation. P=0.001. ICD implantation significantly reduced all-cause mortality in patients with right ventricular systolic dysfunction. Hazard ratio 0.41, but not in patients without right ventricular systolic dysfunction.

Thus, in this post-hoc analysis of the Danish trial, ICD therapy was associated with survival benefit in patients with bi-ventricular heart failure.

In our next paper, Dawn Pedrotty and Volodymyr Kuzmenko and associates, have proposed a concept of using a stretchable, flexible, bio patch, with conductive properties, to attempt to restore conduction across regions in which activation is disrupted. They use carbon nanotube patches, composed of nanofibrillated cellulose, in single wall carbon nanotube ink, 3-D printed in conductive patterns onto bacterial nanocellulose.

Electro anatomic mapping was performed on normal epicardium and repeated over surgically disruptive epicardium, and finally with the patch applied passively. The patch resulted in restored conduction based on mapping.

In our next paper, Ayman Hussein and colleagues developed a fully automated platform to collect patient reported outcomes in a prospective cohort of atrial fibrillation ablation. Two thousand one hundred and seventy-five patients were eligible to receive 10,903 patient reported outcome assessment invitations. More follow up assessments were obtained with automated patient reported outcomes in routine follow-up, compared with routine follow up alone, P > 0.001, which allowed for longer duration of follow up, 378 vs 217 days. By automated patient reported outcomes, a large number of disease specific variables were collected and showed improvement in quality of life. Baseline median AF symptom severity score of 12 and ranged between 2 and 3 on subsequent assessments, P > 0.0001. This improvement was also true for each of the atrial fibrillation symptom severity score components. In patient reported outcomes, there was a significant reduction in atrial fibrillation burden, such as frequency and duration episodes and associated healthcare utilization including emergency visits and hospitalizations after the ablation procedures.

In our next paper, Nicolas Johner, Dipen Shah, and associates, examined the role of post pacing intervals shorter than tachycardia cycling during entrainment mapping. The author studied 24 non-cavotricuspid isthmus dependent macro oriented atrial flutters in 19 consecutive patients. High density electro anatomic activation maps were acquired with a 64-electrode basket catheter of 102 entrainment mapping sites. Post pacing interval difference less than 30 was observed at 72 sites on complete maps of 24 atypical atrial flutters compared to sites with the difference in post pacing intervals 0 to 30, with 45 sites difference in the post pacing interval less than 0 at 27 were more commonly located within isthmuses less than 15mm wide and more frequently located in within 5mm of the leading wave front. It also exhibited slower local conduction, lower voltages in more frequently fractioned electrograms. The authors concluded that in atrial flutter, sites with differences with the post pacing interval are markers of limited width critical isthmuses with slower conduction velocity, while sites with difference in post pacing interval 0 to 30ms are often not in close proximity to the reentrance circuit. Virtual electrode simultaneous down and up stream, antidromic capture of a confined isthmus of slow conduction can explain a difference in the post pacing interval less than 0.

In the next paper, José Manuel Alfonso-Almazán, and associates studied the safety and efficacy parameters associated with catheter-based radiofrequency delivery at the root of the aorta and pulmonary artery. The author studied 34 pigs undergoing in vivo catheter based ablation using continuous contact force and lesion index monitoring during 60 second radiofrequency delivery with an open, irrigated tip catheter. Twenty-eight animals were allocated to groups receiving 40 watts, 50 watts, or 60 watts and acute, chronic arterial damage was quantified by multi photon microscopy in ex vivo samples. Adjacent microlesion were quantified in parallel samples. The remaining 8 pigs, these were used to validate safety and efficacy parameters. Acute collagen elastic alterations were significantly associated with radiofrequency power, although chronic assessment revealed vascular wall recovery in patients without [steam pop 00:06:56]. The main parameters associated with steam pops were median peak temperature greater than 42C, and impedance falls greater than 23 ohms. Unlike other parameters, lesion index values of 9.1 units were associated with the presence of adjacent myocardial lesions in both univariate and multivariate analyses. In the validation group, lesion index values using 40 watts over a range of contact forces correlated with the size of radiofrequency lesions. Lesion index values obtained during 40 watts radiofrequency application reliably monitor safe and effective lesion creation at the root of the great arteries.

In our next paper, Eiichiro Oka and associates examine the prevalence and significance of the early repolarization electrocardiographic pattern and its mechanistic insight based on cardiac magnetic resonance findings in patients with acute myocarditis. The author studied 30 patients with the diagnosis of acute myocarditis. Nine had an early repolarization electrocardiographical pattern, which was defined as a terminal QRS notching or slurring with an amplitude of greater than zero-point millivolts in at least two inferior and/or lateral leads. The early repolarization group, while the remaining 21 cases had broad ST elevation or pathological QAs.

The non-early repolarization group. The cardiac prepotency level was significantly higher in the non-early repolarization group than the early repolarization group. The ECD changes returned to baseline, along with a normalization of the cardiac biomarkers. Nine of the 21 non-early repolarization group patients, but none of the 9 early repolarization groups developed fulminant course of lethal ventricular arrhythmias. T2-weighted cardiac magnetic resonance imaging showed high intensity signals over the entire transmittal left vertical in the non-early repolarization group, where as they were localized to the left ventricle epicardium in early repolarization group. The early repolarization pattern in acute myocarditis was transient and reversible, and was not associated with a worse prognosis. Inflammation or swelling localized to the left ventricular epicardium, due to myocarditis, may provide a mechanistic insight into the early repolarization pattern.

In our next paper, Beatrix Scholz and Jan Sebastian Schulte and associates analyzed whether the histone deacetylase class I and II inhibitor valproic acid is able to attenuate atrial remodeling in CREM-IbΔCx (TG) transgenic mice. A mouse model of extensive atrial remodeling with age dependent progression from spontaneous atrial ectopy to paroxysmal and finally long lasting atrial fibrillation. Valproic acid was administered for 7 or 25 weeks to transgenic and control mice. Valproic acid attenuated many components of atrial remodeling that were present in the transgenic mice.

Valproic acid significantly reduced atrial dilation, cardiomyocyte enlargement, atrial fibrosis, and the disorganization of myocytes ultrastructure. It significantly reduced the occurrence of atrial thrombi, reversed action potential alterations, and finally delayed the onset of atrial fibrillation by 4 to 8 weeks. Increased histone H4 acetylation in atria from valproic acid treated transgenic mice verified effective in in vivo histone deacetylase inhibition. Cardiomyocyte specific genetic inactivation of histone deacetylase HDAC 2 in transgenic mice attenuated the ultrastructural disorganization of myocytes compared to valproic acid. The author suggests that valproic acid, clinically available, well tolerated, and prescribed to many patients for years, has a therapeutic potential to delay the development of atrial remodeling in the onset of atrial fibrillation in patients at risk.

In our next paper, Bence Hegyi and associates measure the major inward currents in their calcium channel and beta-adrenergic dependence under physiologic action potential clamp in rabbit ventricular myocytes in chronic pressure volume overload induced heart failure versus age matched controls. They found that CAM kinase II dependent up regulation of late sodium current in heart failure significantly contributes to the action potential prolongation in increased short-term variability of action potential repolarization, which may lead to increased arrhythmia propensity and is further exacerbated by adrenergic stress.

In a research letter, Arnaud Bisson and associates examined mitral regurgitation in 838, or 10%, of 8675 patients with atrial fibrillation. A total 135, or 16%, had severe mitral regurgitation. During mean follow-up with 2.5 years, 688 ischemic stroke or thromboembolic events were recorded. mitral regurgitation was associated with a non-significant higher risk of these embolic events. After adjustment for anticoagulant and antiplatelet use, CHA2DS2-VASc and HAS-BLED scores, patients with mitral regurgitation tended to have a higher all cause or cardiovascular mortality but had similar risks of ischemic stroke or thromboembolic events, when compared to patients with no mitral regurgitation. Severe mitral regurgitation was also associated with similar risk for ischemic stroke and thromboembolic events when compared with other atrial fibrillation patients. However, our findings indicate that in patients with atrial fibrillation, neither mitral regurgitation nor severe mitral regurgitation, appears to independently be associated with a different risk of ischemic stroke or thromboembolic events. The perceived protective effect of mitral regurgitation against the risk of thromboembolic events is not relevant in atrial fibrillation when using a contemporary risk score scheme, the CHA2DS2-VASc score.

In our final research paper, Jack Z. Li and associates noted that in 2017, an aggregate of four manufacturers of devices yielded 89.6% with the DF-4 ICD implants. While DF-4 and DF-1 leads generally have comparable performance, several concerns over reduced versatility of the DF-4 have been raised. First, to downgrade an ICD with a DF-4 lead to a pacemaker, a generator change, a new right ventricular pace sense lead must be implanted. The DF-4 pin is incompatible with the IS-1 port and there is no straightforward way to bridge this gap. In contrast, the DF-1 IS-1 lead requires only capping of the DF-1 pin. Second, if an ICD with DF-4 lead has either a distal coil or a right ventricular pacing malfunction, a new lead must be implanted. Third, if a ICD with DF-4 lead has a high defibrillation threshold, management requires either a new DF-1 IS-1 lead with an adapter for a subcutaneous array, or an adapter that inserts into the DF-4 port and receives both the DF-4 lead and the DF-1 pin of the subcutaneous lead. Physicians should have the foresight to select DF-1 leads at the time of initial implant in selected circumstances, such as high possibility for elevated defibrillation threshold requiring a subcutaneous lead or array.

That's it for this month! We hope that you'll find the journal to be the go-to place for everyone interested in the field. See ya next time.

This program is copyright American Heart Association 2019.