Response to cardiac resynchronization therapy is determined by intrinsic electrical substrate rather than by its modification.

BACKGROUND: Electrocardiographic mapping (ECM) expresses electrical substrate through magnitude and direction of the activation delay vector (ADV). We investigated to what extent the response to cardiac resynchronization therapy (CRT) is determined by baseline ADV and by ADV modification through CRT and optimization of left ventricular (LV) pacing site. METHODS: ECM was performed in 79 heart failure patients (4 RBBB, 12 QRS < 120 ms, 23 non-specific conduction delay [NICD] and 40 left bundle branch block [LBBB]). 67 patients (QRS ≥ 120 ms) underwent CRT implantation and in 26 patients multiple LV pacing site optimization was performed. ADV was calculated from locations/depolarization times of 2000 virtual epicardial electrodes derived from ECM. Acute response was defined as ≥10% LVdP/dtmax increase, chronic response by composite clinical score at 6 months. RESULTS: During intrinsic conduction, ADV direction was similar in patients with QRS < 120 ms, NICD and LBBB, pointing towards the LV free wall, while ADV magnitude was larger in LBBB (117 ±â€¯25 ms) than in NICD (70 ±â€¯29 ms, P < 0.05) and QRS < 120 ms (52 ±â€¯14 ms, P < 0.05). Intrinsic ADV accurately predicted the acute (AUC = 0.93) and chronic (AUC = 0.90) response to CRT. ADV change by CRT only moderately predicted response (highest AUC = 0.76). LV pacing site optimization had limited effects: +3 ±â€¯4% LVdP/dtmax when compared to conventional basolateral LV pacing. CONCLUSION: The baseline electrical substrate, adequately measured by ADV amplitude, strongly determines acute and chronic CRT response, while the extent of its modification by conventional CRT or by varying LV pacing sites has limited effects.

Outcome of resynchronization therapy on superficial and endocardial electrophysiological findings.

Cardiac resynchronization therapy (CRT) has proven efficacious in the treatment of patients with heart failure and dyssynchronous activation. Currently, we select suitable CRT candidates based on the QRS complex duration (QRSd) and morphology with left bundle branch block being the optimal substrate for resynchronization. To improve CRT response rates, recommendations emphasize attention to electrical parameters both before implant and after it. Therefore, we decided to study activation times before and after CRT on the body surface potential maps (BSPM) and to compare thus obtained results with data from electroanatomical mapping using the CARTO system. Total of 21 CRT recipients with symptomatic heart failure (NYHA II-IV), sinus rhythm, and QRSd >/=150 ms and 7 healthy controls were studied. The maximum QRSd and the longest and shortest activation times (ATmax and ATmin) were set in the BSPM maps and their locations on the chest were compared with CARTO derived time interval and site of the latest (LATmax) and earliest (LATmin) ventricular activation. In CRT patients, all these parameters were measured during both spontaneous rhythm and biventricular pacing (BVP) and compared with the findings during the spontaneous sinus rhythm in the healthy controls. QRSd was 169.7+/-12.1 ms during spontaneous rhythm in the CRT group and 104.3+/-10.2 ms after CRT (p<0.01). In the control group the QRSd was significantly shorter: 95.1+/-5.6 ms (p<0.01). There was a good correlation between LATmin(CARTO) and ATmin(BSPM). Both LATmin and ATmin were shorter in the control group (LATmin(CARTO) 24.8+/-7.1 ms and ATmin(BSPM) 29.6+/-11.3 ms, NS) than in CRT group (LATmin(CARTO) was 48.1+/-6.8 ms and ATmin(BSPM) 51.6+/-10.1 ms, NS). BVP produced shortening compared to the spontaneous rhythm of CRT recipients (LATmin(CARTO) 31.6+/-5.3 ms and ATmin(BSPM) 35.2+/-12.6 ms; p<0.01 spontaneous rhythm versus BVP). ATmax exhibited greater differences between both methods with higher values in BSPM: in the control group LATmax(CARTO) was 72.0+/-4.1 ms and ATmax (BSPM) 92.5+/-9.4 ms (p<0.01), in the CRT candidates LATmax(CARTO) reached only 106.1+/-6.8 ms whereas ATmax(BSPM) 146.0+/-12.1 ms (p<0.05), and BVP paced rhythm in CRT group produced improvement with LATmax(CARTO) 92.2+/-7.1 ms and ATmax(BSPM) 130.9+/-11.0 ms (p<0.01 before and during BVP). With regard to the propagation of ATmin and ATmax on the body surface, earliest activation projected most often frontally in all 3 groups, whereas projection of ATmax on the body surface was more variable. Our results suggest that compared to invasive electroanatomical mapping BSPM reflects well time of the earliest activation, however provides longer time-intervals for sites of late activation. Projection of both early and late activated regions of the heart on the body surface is more variable than expected, very likely due to changed LV geometry and interposed tissues between the heart and superficial ECG electrode.

[New strategies and technologies for ablation of atrial fibrillation : Where do we go?] / Neue Strategien und Technologien für die Ablation von Vorhofflimmern : "Where do we go?".

Catheter-based ablation is an established treatment option for patients with symptomatic atrial fibrillation (AF). Pulmonary vein isolation is the established cornerstone of all ablation strategies. However, the rate of electrical reconduction of previously isolated pulmonary veins is high and associated with recurrence of AF. Novel and innovative mapping and ablation systems are being developed or are under clinical evaluation aiming for higher durability of pulmonary vein isolation. Additional ablation strategies for patients with recurrence of AF despite persistent isolation of the pulmonary veins are under evaluation. These ablation strategies include ablation of complex fractionated atrial electrograms, linear lesions, rotors or drivers, fibrotic areas or ablation of extrapulmonary triggers. The true clinical benefit of these additional ablation strategies can only be assessed if the pulmonary veins are persistently isolated.

Developing a novel comprehensive framework for the investigation of cellular and whole heart electrophysiology in the in situ human heart: historical perspectives, current progress and future prospects.

Understanding the mechanisms of fatal ventricular arrhythmias is of great importance. In view of the many electrophysiological differences that exist between animal species and humans, the acquisition of basic electrophysiological data in the intact human heart is essential to drive and complement experimental work in animal and in-silico models. Over the years techniques have been developed to obtain basic electrophysiological signals directly from the patients by incorporating these measurements into routine clinical procedures which access the heart such as cardiac catheterisation and cardiac surgery. Early recordings with monophasic action potentials provided valuable information including normal values for the in vivo human heart, cycle length dependent properties, the effect of ischaemia, autonomic nervous system activity, and mechano-electric interaction. Transmural recordings addressed the controversial issue of the mid myocardial "M" cell. More recently, the technique of multielectrode mapping (256 electrodes) developed in animal models has been extended to humans, enabling mapping of activation and repolarisation on the entire left and right ventricular epicardium in patients during cardiac surgery. Studies have examined the issue of whether ventricular fibrillation was driven by a "mother" rotor with inhomogeneous and fragmented conduction as in some animal models, or by multiple wavelets as in other animal studies; results showed that both mechanisms are operative in humans. The simpler spatial organisation of human VF has important implications for treatment and prevention. To link in-vivo human electrophysiological mapping with cellular biophysics, multielectrode mapping is now being combined with myocardial biopsies. This technique enables region-specific electrophysiology changes to be related to underlying cellular biology, for example: APD alternans, which is a precursor of VF and sudden death. The mechanism is incompletely understood but related to calcium cycling and APD restitution. Multielectrode sock mapping during incremental pacing enables epicardial sites to be identified which exhibit marked APD alternans and sites where APD alternans is absent. Whole heart electrophysiology is assessed by activation repolarisation mapping and analysis is performed immediately on-site in order to guide biopsies to specific myocardial sites. Samples are analysed for ion channel expression, Ca(2+)-handling proteins, gap junctions and extracellular matrix. This new comprehensive approach to bridge cellular and whole heart electrophysiology allowed to identify 20 significant changes in mRNA for ion channels Ca(2+)-handling proteins, a gap junction channel, a Na(+)-K(+) pump subunit and receptors (particularly Kir 2.1) between the positive and negative alternans sites.

[Interventional electrophysiology in cardiac MRI : what is the current status?]. / Interventionelle Elektrophysiologie in der kardialen MRT : Wie ist der aktuelle Stand?

The ablation of simple and complex cardiac arrhythmias has become a first-line therapy in interventional cardiology and is mainly guided by conventional fluoroscopy. Cardiac magnetic resonance imaging (cMRI) allows exact three-dimensional (3D) visualization of complex anatomical structures and serves in the planning and implementation of ablation procedures. Post-procedural lesion visualization using cMRI can assess the success of ablation therapy and may distinguish potential complications. Performing ablation directly in the MRI scanner, with the option of anatomical substrate imagining, exact catheter navigation and real-time lesion visualization, holds the promise of improving success rates and safety in the interventional therapy of simple and complex arrhythmias.

Electrocardiologic and related methods of non-invasive detection and risk stratification in myocardial ischemia: state of the art and perspectives.

BACKGROUND: Electrocardiographic methods still provide the bulk of cardiovascular diagnostics. Cardiac ischemia is associated with typical alterations in cardiac biosignals that have to be measured, analyzed by mathematical algorithms and allegorized for further clinical diagnostics. The fast growing fields of biomedical engineering and applied sciences are intensely focused on generating new approaches to cardiac biosignal analysis for diagnosis and risk stratification in myocardial ischemia. OBJECTIVES: To present and review the state of the art in and new approaches to electrocardiologic methods for non-invasive detection and risk stratification in coronary artery disease (CAD) and myocardial ischemia; secondarily, to explore the future perspectives of these methods. METHODS: In follow-up to the Expert Discussion at the 2008 Workshop on "Biosignal Analysis" of the German Society of Biomedical Engineering in Potsdam, Germany, we comprehensively searched the pertinent literature and databases and compiled the results into this review. Then, we categorized the state-of-the-art methods and selected new approaches based on their applications in detection and risk stratification of myocardial ischemia. Finally, we compared the pros and cons of the methods and explored their future potentials for cardiology. RESULTS: Resting ECG, particularly suited for detecting ST-elevation myocardial infarctions, and exercise ECG, for the diagnosis of stable CAD, are state-of-the-art methods. New exercise-free methods for detecting stable CAD include cardiogoniometry (CGM); methods for detecting acute coronary syndrome without ST elevation are Body Surface Potential Mapping, functional imaging and CGM. Heart rate variability and blood pressure variability analyses, microvolt T-wave alternans and signal-averaged ECG mainly serve in detecting and stratifying the risk for lethal arrythmias in patients with myocardial ischemia or previous myocardial infarctions. Telemedicine and ambient-assisted living support the electrocardiological monitoring of at-risk patients. CONCLUSIONS: There are many promising methods for the exercise-free, non-invasive detection of CAD and myocardial ischemia in the stable and acute phases. In the coming years, these new methods will help enhance state-of-the-art procedures in routine diagnostics. The future can expect that equally novel methods for risk stratification and telemedicine will transition into clinical routine.

Electrocardiographic body surface mapping: potential tool for the detection of transient myocardial ischemia in the 21st century?

Coronary artery disease (CAD) is one of the leading causes of cardiovascular mortality and morbidity worldwide. CAD presents as a wide spectrum of clinical disease from stable angina to ST segment elevation myocardial infarction. The 12-lead electrocardiogram (ECG) has been the main tool for the diagnosis of these events for almost a century but is limited in its diagnostic ability. For patients with suspected angina, the exercise tolerance test is often used to provoke and detect stress-induced ischemia but does not provide a definitive answer in a substantial proportion of patients. Body surface mapping (BSM) is a technique that samples multiple points around the thorax to provide a more comprehensive electrocardiographic data set than the conventional 12-lead ECG. Moreover, recent preliminary data demonstrate that BSM can detect and display transient regional myocardial ischemia in an intuitive fashion, employing subtraction color mapping, making it potentially valuable for diagnosing CAD causing transient regional ischemia. Research is ongoing to determine the full extent of its utility.

Imaging in catheter ablation for atrial fibrillation: enhancing the clinician's view.

Catheter ablation is an effective treatment for symptomatic atrial fibrillation. A thorough understanding of the left atrium anatomy and its adjacent structures is critical for the success of the procedure and for avoiding complications. Pre-procedural imaging aims at determining left atrial size, anatomy, and function and is also used to rule out an atrial thrombus. During the procedure, while fluoroscopy remains the gold standard imaging modality for guiding transseptal catheterization and catheter ablation, numerous other imaging modalities have been developed to improve 3D navigation and ablation. Finally, post-operative imaging intends to monitor heart function and to search for potential complications like pulmonary vein stenosis or the rare but dramatic atrio-oesophageal fistula. This review discusses the relative merits of all imaging modalities available in the context of catheter ablation of atrial fibrillation.

New generation of electro-anatomic mapping: full intracardiac ultrasound image integration.

Surrogate electro-anatomic-derived geometries are used as the three-dimensional (3D) basis for mapping of cardiac arrhythmias. While merged computed tomography (CT) imaging may provide stellar pulmonary vein (PV) and left atrial (LA) anatomy, the applied scans must be obtained prior to ablation, and may not reflect physiologic conditions at the time of intervention. Patient-specific, ultrasound-derived 3D imaging has been developed as an alternative basis for new generation electro-anatomic mapping. An electro-anatomic sensor positioned at the tip of the phased-array intracardiac ultrasound catheter, provides the means to specify both location and orientation of each image as the 'context' for creating the 3D volumes for co-registration with electro-anatomic mapping. Specific anatomic details such as the pulmonary veins, membranous fossa, papillary muscles, or valve structures derived from real-time imaging can also be integrated into each segmented volume. This presentation reviews the basis and methods for this novel multi-modality image fusion for the creation of robust, nearly real-time anatomic images for guiding electro-anatomic mapping and ablation without requiring pre-acquired CT image sets, with accompanying limitations.

Managing catheter ablation for atrial fibrillation: the role of echocardiography.

Atrial fibrillation (AF) is a common arrhythmia associated with the serious clinical consequences of systemic thrombo-embolism and heart failure. Catheter ablation for AF is an evolving treatment option for patients with drug-refractory paroxysmal and persistent AF. The ablation procedure relies on precise knowledge of the left atrium, left atrial appendage, and pulmonary venous anatomy and function. Echocardiography is an integral component of multiple imaging modalities which contribute to its success. Both transoesophageal echocardiography and transthoracic echocardiography provide essential anatomical and functional information to guide all aspects of management. This article reviews the role of echocardigraphy in AF ablation, from appropriate patient selection and pre-procedural screening, to evaluating complications and determining the need for long-term anticoagulation.

Mapping techniques for atrial fibrillation ablation.

Atrial fibrillation (AF) is a common arrhythmia. Although significant work still needs to be done, recent advances in understanding the mechanism of AF have led to the development of elegant catheter mapping techniques for ablation of AF. These improved mapping techniques are complemented by an evolution in various imaging and navigational technologies, several of which can now be combined in a process called registration, so that the physician no longer needs to rely solely on a mental image of the anatomy of the left atrium and the pulmonary vein while attempting to ablate the region. Ongoing advances in mapping technique will increase safety and efficacy and it is likely that AF ablation will become the first-line therapy in most patients with this complicated arrhythmia.

Mapping arrhythmias in the failing heart: from Langendorff to patient.

Sudden cardiac death due to ventricular arrhythmias is a major cause of mortality in patients with heart failure (HF). As HF develops, a host of changes occur at multiple levels, spanning the spectrum from subcellular/molecular to organ-system levels. These changes, collectively referred to as "cardiac remodeling," predispose to electrical disturbances via multiple mechanisms. In humans, most arrhythmias are reentrant by nature, involving circulatory wavefront(s) that excite the heart in rapid, irregular succession. Hence, by definition, reentrant excitation occurs at the multicellular intact tissue level, and therefore, a complete understanding of its dynamics and underlying mechanisms requires investigation of electrophysiological properties (such as action potentials and calcium transients) in intact tissue preparations where cells are electrically coupled to one another. While molecular and cellular studies are critical for identifying changes in individual myocytes, only recently have we begun to understand how these complex changes can create an environment ripe for arrhythmias. In particular, the integrative technique of optical action potential mapping was used in recent years to address key questions regarding changes in network electrical properties of the failing myocardium. In the present manuscript, we review recent findings from mapping studies in the experimental laboratory as they relate to the characterization of the arrhythmic substrate of the failing heart, followed by a discussion of clinical mapping approaches used to identify key characteristics of atrial and ventricular arrhythmias in patients with HF.

Three dimensional mapping of atrial fibrillation: techniques and necessity.

Over the past 5 years, catheter ablation of atrial fibrillation (AF) has evolved from an experimental procedure to one that is now performed throughout the world. The rapid and widespread acceptance of this procedure reflects encouraging reports of the safety and efficacy of catheter ablation of AF. The improved outcomes of catheter ablation of AF have resulted from a combination of increasing clinical experience, but also several important technological advances. One of the most important of these has been the development and widespread utilization of three dimensional mapping systems during AF ablation The purpose of this article is to briefly review the current status and clinical role of three dimensional mapping systems in catheter ablation of AF.