\documentclass[10pt]{article}

\usepackage{fullpage}
\usepackage{setspace}
\usepackage{parskip}
\usepackage{titlesec}
\usepackage[section]{placeins}
\usepackage{xcolor}
\usepackage{breakcites}
\usepackage{lineno}
\usepackage{hyphenat}





\PassOptionsToPackage{hyphens}{url}
\usepackage[colorlinks = true,
            linkcolor = blue,
            urlcolor  = blue,
            citecolor = blue,
            anchorcolor = blue]{hyperref}
\usepackage{etoolbox}
\makeatletter
\patchcmd\@combinedblfloats{\box\@outputbox}{\unvbox\@outputbox}{}{%
  \errmessage{\noexpand\@combinedblfloats could not be patched}%
}%
\makeatother


\usepackage{natbib}




\renewenvironment{abstract}
  {{\bfseries\noindent{\abstractname}\par\nobreak}\footnotesize}
  {\bigskip}

\titlespacing{\section}{0pt}{*3}{*1}
\titlespacing{\subsection}{0pt}{*2}{*0.5}
\titlespacing{\subsubsection}{0pt}{*1.5}{0pt}


\usepackage{authblk}


\usepackage{graphicx}
\usepackage[space]{grffile}
\usepackage{latexsym}
\usepackage{textcomp}
\usepackage{longtable}
\usepackage{tabulary}
\usepackage{booktabs,array,multirow}
\usepackage{amsfonts,amsmath,amssymb}
\providecommand\citet{\cite}
\providecommand\citep{\cite}
\providecommand\citealt{\cite}
% You can conditionalize code for latexml or normal latex using this.
\newif\iflatexml\latexmlfalse
\providecommand{\tightlist}{\setlength{\itemsep}{0pt}\setlength{\parskip}{0pt}}%

\AtBeginDocument{\DeclareGraphicsExtensions{.pdf,.PDF,.eps,.EPS,.png,.PNG,.tif,.TIF,.jpg,.JPG,.jpeg,.JPEG}}

\usepackage[utf8]{inputenc}
\usepackage[ngerman,english]{babel}



\usepackage{float}








\begin{document}

\title{A Ripple in Time: Timing is Everything}



\author[1]{Tarek Zghaib}%
\author[1]{David Lin}%
\affil[1]{Hospital of the University of Pennsylvania}%


\vspace{-1em}



  
  \date{May 27, 2024}


\begingroup
\let\center\flushleft
\let\endcenter\endflushleft
\maketitle
\endgroup








\sloppy


Editorial

\textbf{A Ripple in Time: Timing is everything}

Tarek Zghaib, MD*; David Lin, MD*

\emph{* Division of Cardiovascular Medicine, Section for Cardiac
Electrophysiology, Hospital of the University of Pennsylvania,
Philadelphia, Pennsylvania. 1 Convention Boulevard,
2\textsuperscript{nd} floor City Side, Philadelphia, PA 19104, United
States.}

Corresponding Author:

Word Count: 973

References: 7

Catheter ablation is an established and effective treatment modality for
management of drug refractory symptomatic outflow tract premature
ventricular contractions (PVCs). However, identification of the true
site of origin when mapping is key for a successful ablation. Outflow
tract PVCs may originate from the epicardium {[}left ventricular (LV)
summit{]}, endocardium {[}left or right outflow tracts (LVOT and
RVOT){]}, or mid-myocardium (intramural). There are currently no clear
ECG criteria identified to definitively indicate an intramural origin of
outflow tract PVCs. The traditional approach to mapping the PVC origin
entails a combination of pace-mapping as well as activation mapping. The
latter consists of assigning a local activation time to each point
relative to a fixed reference, and identifying the earliest, pre-QRS
ventricular signal.

The widespread adoption of multipolar mapping catheters has heralded
innovative and novel approaches to performing automated, high-density
activation mapping of PVCs. Activation mapping of outflow tract PVCs can
sometimes be challenging for various reasons. Manual annotation of
activation times is often required, rendering the process arduous and
time-consuming. Assigning earliest signal in areas of scar or conduction
slowing may be arbitrary and challenging due to low-amplitude
multi-component electrograms (EGMs) in those areas. Low-amplitude EGMs
may also represent far-field potentials in adjacent tissue, such as
mid-myocardial PVCs originating from deeper in the septum or in the
opposite chamber.\textsuperscript{1} These EGMs would be excluded from
activation mapping, increasing procedural failure rate due to ablation
at PVC endocardial breakout sites rather than at its more distal site of
origin.

Ripple mapping (Biosense Webster, Irvine, CA) was developed to remedy
the short-comings of traditional activation
mapping,\textsuperscript{2}and has been validated for ventricular
tachycardia, atrial flutter and atrial tachycardias
(AT).\textsuperscript{3--5} Ripple maps provide real-time display of
dynamic bars of varying heights depending on the amplitude of the local
EGM over time, and ideally would obviate the need for manual annotation
or interpolation over unmapped myocardium.\textsuperscript{6} By
displaying the entirety of the EGM over time, Ripple mapping allows the
operator to identify potentially relevant far-field sites such as
mid-myocardial or epicardial PVC foci, or delayed conduction in regions
of scar.\textsuperscript{4} The Ripple-AT study randomized 83 patients
with AT to Ripple mapping vs isochronal activation mapping and
demonstrated higher rates of AT termination with the
former.\textsuperscript{3} In patients with arrhythmogenic right
ventricular cardiomyopathy, complete ablation of conduction channels
identified using Ripple mapping led to improved rates of VT-free
survival during follow-up.\textsuperscript{4}

In this issue of the \emph{Journal,} Arps et al evaluated the utility of
Ripple mapping as an adjunct to activation mapping during ablation of
septal outflow tract PVCs. In a series of 55 patients undergoing PVC
ablation in the LVOT or posterior RVOT, their study retrospectively
compared the earliest activation point (EA) obtained with activation
mapping to the earliest Ripple signal (ERS) on Ripple mapping and to
successful ablation points. Mapping was done in both chambers in most
patients, including the coronary sinus in half the cohort. Chamber
concordance between ERS and EA was found in 88\% of cases and was
associated with higher rates of successful PVC suppression. Distance
between EA and ERS was associated with procedural success and was
\textgreater{}5 mm in 52\% of cases. Discordance was more likely in
patients who had prior PVC ablation and was associated with higher rates
of requiring multi-site ablations. Interestingly, there was no
difference in the distance between EA vs. ERS with sites of successful
ablation, albeit analyzed in a small subset of patients. We congratulate
Arps et al. for their well-written, clinically valuable manuscript. As
evidenced by the study results, Ripple mapping may improve localization
of septal outflow tract PVCs beyond traditional activation alone.
Discordance between EA and ERS may suggest mid-myocardial or epicardial
PVC focus, seen as far-field low-amplitude EGMs on Ripple mapping. This
finding should prompt the operator to perform more extensive mapping
beyond LV and RV endocardium to identify more distal PVC
foci.\textsuperscript{7} With the more recent availability of better
tools to map the coronary venous system, the ability to identify the
intramural substrate for the difficult to reach locations in the outflow
tract region has further improved the success of ablation in this
region.

The study by Arps et al. raises important questions that require further
research. The retrospective nature of this study limits clinical
applicability of the results due to potential confounders such as
operator experience, point sample density, type of mapping catheters,
variable intra-procedural use of Ripple mapping, etc. Larger prospective
studies are needed to validate the impact of Ripple mapping on PVC
ablation outcomes. Furthermore, whether early low-amplitude fractionated
Ripple signals represent near-field scar or far-field mid-myocardial PVC
requires more investigation. Operators need to be aware of the
shortcomings of Ripple mapping technology such as influence of catheter
orientation or underlying rhythm on EGM amplitude, its dependence on
density of mapping points obtained, potential interference from noise
artifact, and potential subjectivity in interpreting Ripple signals.

In conclusion, Arps et al. introduce Ripple mapping as an additional
tool in the armamentarium to localize the site of origin of PVCs and the
potential impact on the ablation strategy, particularly for
mid-myocardial or epicardial outflow tract PVCs where traditional
activation mapping may be inadequate or particularly challenging. As
this study shows, neither approach in isolation is sufficient. To
achieve procedural success, electrophysiologists should always remain
vigilant to the nuances of the raw EGM rather than blindly relying on
automated algorithms provided by mapping systems. A comprehensive
understanding and analysis of ECG characteristics of the outflow tract
region PVCs, understanding the anatomy of the outflow tract region
including the surrounding coronary venous system, coupled with the use
of imaging modalities such as intracardiac echocardiography and cardiac
MRI, and high density mapping, further enhanced by the use of mapping
technologies such as Ripple mapping to provide functional as well as
anatomic information could further improve the safety and efficacy of
ablation of outflow tract PVCs.

References

1. De Sa DDC, Thompson N, Stinnett-Donnelly J, et al. Electrogram
fractionation: The relationship between spatiotemporal variation of
tissue excitation and electrode spatial resolution. \emph{Circ
Arrhythmia Electrophysiol} . 2011;4(6):909-916.
doi:10.1161/CIRCEP.111.965145

2. Luther V, Cortez-Dias N, Carpinteiro L, et al. Ripple mapping:
Initial multicenter experience of an intuitive approach to overcoming
the limitations of 3D activation mapping. \emph{J Cardiovasc
Electrophysiol} . 2017;28(11):1285-1294. doi:10.1111/JCE.13308

3. Luther V, Agarwal S, Chow A, et al. Ripple-AT Study: A Multicenter
and Randomized Study Comparing 3D Mapping Techniques During Atrial
Tachycardia Ablations. \emph{Circ Arrhythmia Electrophysiol} .
2019;12(8). doi:10.1161/CIRCEP.118.007394

4. Xie S, Kubala M, Liang JJ, et al. Utility of ripple mapping for
identification of slow conduction channels during ventricular
tachycardia ablation in the setting of arrhythmogenic right ventricular
cardiomyopathy. \emph{J Cardiovasc Electrophysiol} . 2019;30(3):366-373.
doi:10.1111/JCE.13819

5. Howard TS, Valdes SO, Zobeck MC, et al. Ripple mapping: A precise
tool for atrioventricular nodal reentrant tachycardia ablation. \emph{J
Cardiovasc Electrophysiol} . 2022;33(6):1183-1189. doi:10.1111/JCE.15491

6. Linton NWF, Koa-Wing M, Francis DP, et al. Cardiac ripple mapping: a
novel three-dimensional visualization method for use with
electroanatomic mapping of cardiac arrhythmias. \emph{Hear Rhythm} .
2009;6(12):1754-1762. doi:10.1016/J.HRTHM.2009.08.038

7. Brice\selectlanguage{ngerman}ño DF, Enriquez A, Liang JJ, et al. Septal Coronary Venous
Mapping to Guide Substrate Characterization and Ablation of Intramural
Septal Ventricular Arrhythmia. \emph{JACC Clin Electrophysiol} .
2019;5(7):789-800. doi:10.1016/J.JACEP.2019.04.011

\selectlanguage{english}
\FloatBarrier
\end{document}

