Tomás Datino

Mechanisms by Which Adenosine Restores Conduction in Dormant Canine Pulmonary Veins

Background— Adenosine acutely reconnects pulmonary veins (PVs) after radiofrequency application, revealing “dormant conduction” and identifying PVs at risk of reconnection, but the underlying mechanisms are unknown. Methods and Results— Canine PV and left-atrial (LA) action potentials were recorded with standard microelectrodes and ionic currents with whole-cell patch clamp before and after adenosine perfusion. PVs were isolated with radiofrequency current application in coronary-perfused LA-PV preparations. Adenosine abbreviated action potential duration similarly in PV and LA but significantly hyperpolarized resting potential (by 3.9±0.5%; P<0.05) and increased dV/dtmax (by 34±10%) only in PV. Increased dV/dtmax was not due to direct effects on INa, which was reduced similarly by adenosine in LA and PV but correlated with resting-potential hyperpolarization (r=0.80). Adenosine induced larger inward rectifier K+current (IKAdo) in PV (eg, –2.28±0.04 pA/pF; –100 mV) versus LA (–1.28±0.16 pA/pF). Radiofrequency ablation isolated PVs by depolarizing resting potential to voltages positive to –60 mV. Adenosine restored conduction in 5 dormant PVs, which had significantly more negative resting potentials (–57±6 mV) versus nondormant (–46±5 mV, n=6; P<0.001) before adenosine. Adenosine hyperpolarized both, but more negative resting-potential values after adenosine in dormant PVs (–66±6 mV versus –56±6 mV in nondormant; P<0.001) were sufficient to restore excitability. Adenosine effects on resting potential and conduction reversed on washout. Spontaneous recovery of conduction occurring in dormant PVs after 30 to 60 minutes was predicted by the adenosine response. Conclusions— Adenosine selectively hyperpolarizes canine PVs by increasing IKAdo. PVs with dormant conduction show less radiofrequency-induced depolarization than nondormant veins, allowing adenosine-induced hyperpolarization to restore excitability by removing voltage-dependent INa inactivation and explaining the restoration of conduction in dormant PVs.

Noninvasive Identification of Ventricular Tachycardia-Related Conducting Channels Using Contrast-Enhanced Magnetic Resonance Imaging in Patients With Chronic Myocardial Infarction Comparison of Signal Intensity Scar Mapping and Endocardial Voltage Mapping

OBJECTIVES We performed noninvasive identification of post-infarction sustained monomorphic ventricular tachycardia (SMVT)-related slow conduction channels (CC) by contrast-enhanced magnetic resonance imaging (ceMRI). BACKGROUND Conduction channels identified by voltage mapping are the critical isthmuses of most SMVT. We hypothesized that CC are formed by heterogeneous tissue (HT) within the scar that can be detected by ceMRI. METHODS We studied 18 consecutive VT patients (SMVT group) and 18 patients matched for age, sex, infarct location, and left ventricular ejection fraction (control group). We used ceMRI to quantify the infarct size and differentiate it into scar core and HT based on signal-intensity (SI) thresholds (>3 SD and 2 to 3 SD greater than remote normal myocardium, respectively). Consecutive left ventricle slices were analyzed to determine the presence of continuous corridors of HT (channels) in the scar. In the SMVT group, color-coded shells displaying ceMRI subendocardial SI were generated (3-dimensional SI mapping) and compared with endocardial voltage maps. RESULTS No differences were observed between the 2 groups in myocardial, necrotic, or heterogeneous mass. The HT channels were more frequently observed in the SMVT group (88%) than in the control group (33%, p < 0.001). In the SMVT group, voltage mapping identified 26 CC in 17 of 18 patients. All CC corresponded, in location and orientation, to a similar channel detected by 3-dimensional SI mapping; 15 CC were related to 15 VT critical isthmuses. CONCLUSIONS SMVT substrate can be identified by ceMRI scar heterogeneity analysis. This information could help identify patients at risk of VT and facilitate VT ablation.

Atrial fibrillation ablation: translating basic mechanistic insights to the patient.

Atrial fibrillation (AF) ablation is widely performed and is progressively supplanting drug therapy. Catheter-based AF ablation modalities have evolved progressively in parallel to our understanding of underlying mechanisms. Initial attempts to mimic the surgical maze procedure, which were based on the multiple wavelet model, failed because of adverse outcomes and insufficient effectiveness. A major advance was the targeting of pulmonary veins, which is highly effective for paroxysmal AF. Active research on the underlying mechanisms continues. The main challenge is reconnection, but procedures to minimize this are being developed. Ablation procedures for persistent AF are presently limited by suboptimal success rates and long-term disease progression that causes recurrences. Basic research into the underlying mechanisms has led to promising driver mechanism-directed clinical approaches along with pathways toward the prevention of atrial remodeling. Here, we review the role of basic research in the development of presently used AF-ablation procedures and look toward future contributions in improving outcomes.

El anciano con cardiopatía terminal

El objetivo de este documento del Grupo de Estudio «El anciano con cardiopatia terminal», de la Seccion de Cardiologia Geriatrica de la Sociedad Espanola de Cardiologia, es aportar un punto de vista experto que permita un mejor conocimiento de la situacion y una mejora en el manejo y la toma de decisiones en los ultimos dias de vida del paciente de edad avanzada que sufre una cardiopatia. Los cardiopatas ancianos constituyen un grupo heterogeneo y es necesaria una valoracion exhaustiva, especialmente de los factores que condicionan el pronostico (cardiopatia, comorbilidad, situacion funcional y datos de fragilidad) antes de tomar decisiones, sobre todo aquellas que conlleven limitacion del esfuerzo terapeutico como las ordenes de no reanimar o la desactivacion de desfibriladores automaticos implantables. Los ancianos con cardiopatias terminales tienen derecho a disponer de una serie de cuidados y atenciones, entre ellos no sufrir inutilmente, respeto a su libertad de conciencia, conocer su situacion, opinar sobre posibles intervenciones y recibir asistencia psicoespiritual. Los cuidados paliativos deben dirigirse al control de los sintomas tras el diagnostico de la enfermedad incurable y no iniciarse unicamente en la fase de agonia. Estos cuidados estan poco desarrollados en las cardiopatias y deben de tenerse presentes en los ancianos con insuficiencia cardiaca avanzada. Su objetivo es conseguir el maximo bienestar para el paciente desde un punto de vista integral, mejorar su calidad de vida antes del fallecimiento y evitar el empleo de tratamientos agresivos que consumen recursos sin resultados.

Differential effectiveness of pharmacological strategies to reveal dormant pulmonary vein conduction: A clinical-experimental correlation

BACKGROUND Atrial fibrillation recurs in ∼30%-40% of patients after pulmonary vein (PV) isolation (PVI) procedures, often because of restored PV-left atrial (LA) conduction. Adenosine or isoproterenol are used clinically to reveal dormant PV conduction and guide additional ablation. OBJECTIVE The purpose of this study was to assess the differential efficacy of adenosine and/or isoproterenol in revealing dormant PV conduction. METHODS In 25 patients undergoing PVI, dormant conduction was assessed sequentially in response to intravenous adenosine, isoproterenol, and adenosine plus isoproterenol in 100 PVs. To study mechanisms, PVs were isolated by radiofrequency ablation in coronary-perfused canine LA-PV preparations. After PVI, resting membrane potential from PV cells was recorded before and after 1 mM adenosine, 1 μM isoproterenol, 1 μM isoproterenol plus 1 mM adenosine, or no drug (controls). RESULTS Clinical PVI was successful in all 100 PVs, with dormant conduction in 31. Sensitivity for dormant conduction was isoproterenol 10%; adenosine 87% (P <.001 vs. isoproterenol); and isoproterenol + adenosine 100% (P = .13 vs. adenosine). Dormant PV conduction in vitro was revealed with adenosine (53%) and adenosine + isoproterenol (60%) but not with isoproterenol alone or in controls (P <.01). Radiofrequency lesions producing PVI depolarized resting membrane potential, causing inexcitability. Postablation, resting membrane potential hyperpolarized after both adenosine and isoproterenol, but adenosine-induced changes were greater (9.1 ± 0.6 mV, vs. 3.8 ± 0.6 mV; P <0.001), with no significant additional effect when isoproterenol was added to adenosine. CONCLUSION Adenosine is superior to isoproterenol in revealing dormant PVs clinically and experimentally because of more effective adenosine-induced hyperpolarization. Adding isoproterenol to adenosine had no significant additional value.

Actualización en cardiología geriátrica

This article contains a review of the main developments in the field of geriatric cardiology reported during 2011. The principle focus is on research into the characteristics of elderly patients with heart failure, arrhythmias (e.g. into atrial fibrillation and implantable cardioverter-defibrillators), ischemic heart disease and percutaneous interventions.

Differences in Ventriculoatrial Intervals During Entrainment and Tachycardia: A Simpler Method for Distinguishing Paroxysmal Supraventricular Tachycardia with Long Ventriculoatrial Intervals

VA Intervals to Distinguish PSVT. Introduction: Usefulness of the interval between the last pacing stimulus and the last entrained atrial electrogram (SA) minus the tachycardia ventriculoatrial (VA) interval in the differential diagnosis of supraventricular tachycardias with long (>100 ms) VA intervals has not been prospectively studied in a large series of patients. Our objective was to assess the usefulness of the difference SA–VA in diagnosing the mechanism of those tachycardias in patients without preexcitation. The results were compared with those obtained using the corrected return cycle (postpacing interval—tachycardia cycle length—atrioventricular [AV] nodal delay).

Identification of conduction gaps in the ablation line during left atrium circumferential ablation: Facilitation of pulmonary vein disconnection after endpoint modification according to electrogram characteristics

BACKGROUND Left atrium circumferential ablation (LACA) is a simple, effective treatment for atrial fibrillation (AF), but many pulmonary veins (PV) are not disconnected because of conduction gaps (CG) in the ablation line. OBJECTIVE This study defined the electrogram characteristics at the CGs and at the PV- left atrium (LA) connection site and assessed the effect of modifying ablation endpoints at these sites. METHODS Forty consecutive patients underwent LACA. Phase I: In 15 patients, electrogram characteristics at the LA-PV connection, CGs at the ablation line, and PV disconnection rate were evaluated during LACA with current ablation endpoints (80% reduction in electrogram amplitude or 0.1 mV). Phase II: 25 patients underwent LACA with modified endpoints according to the results of Phase I. RESULTS Phase I: Fifty-five PVs were analyzed, 17 during sinus rhythm (SR) and 38 during AF. LA-PV connections were characterized by multicomponent electrograms (ME) without an isoelectric line (0.45 +/- 0.43 mV, 77 +/- 21 ms). After LACA, 55% of PVs were disconnected. In 85% of nondisconnected veins, ME (0.11 +/- 0.02 mV) were recorded at CGs where ablation caused PV disconnection. Phase II: Ninety-five PVs, 52 during AF and 43 during SR underwent LACA with modified ablation endpoints at ME sites: Disappearance of late component and voltage reduction to <0.05 mV. Eighty-five per cent of PV were disconnected (95% in SR and 77 % in AF, P <.01). CONCLUSION MEs identify LA-PV connections and CGs. Modification of ablation endpoints at these sites should facilitate PV disconnection during LACA.

Dominant frequency differences in atrial fibrillation patients with and without left ventricular systolic dysfunction.

AIMS The aim of this study was to determine the mechanisms of atrial fibrillation (AF) in patients with left ventricular systolic dysfunction (LVSD). METHODS AND RESULTS Dominant frequency (DF) spatiotemporal stability was studied in 15 patients with persistent AF (PEAF) and LVSD (Group I), 15 with PEAF without LVSD (Group II), and 10 with paroxysmal AF (PAAF) without LVSD (Group III). Dominant frequencies were analysed at 536 sites at baseline (DF1) and 26 +/- 12 min later (DF2). A DF1-DF2 difference of <or=0.5 Hz was found in 77, 70, and 48% of sites in Groups I, II, and III (P < 0.001). Maximal DF1 and DF2 were recorded at the same site in 12/15, 11/15, and 0/10 patients in Groups I, II, and III, respectively (P < 0.01). Gradient differences: Group I, DFs were higher at left atrium appendage (LAA) than at anterior (A) LA (ALA), pulmonary vein-left atrial junction (PV-LAJ), and posterior (P) LA (PLA) (7.4 +/- 1.1 vs. 6.6 +/- 1 vs. 6.8 +/- 0.8 vs. 6.8 +/- 0.7 Hz, P < 0.05); Group II, no differences; Group III, DF was higher at PV-LAJ than at LAA, AL, and PLA (6 +/- 1.2 vs. 5.3 +/- 1.1 vs. 5.2 +/- 0.9 vs. 5.4 +/- 1.1 Hz, P < 0.05). CONCLUSION Dominant frequency stability supports stable arrhythmia sources as the mechanism of PEAF with (without) LVSD, but not of PAAF.

Ergonovine provocative test in Caucasian patients with left ventricular apical ballooning syndrome

Of a series of 346 consecutive patients with chest pain and no significant coronary stenosis studied with ergonovine provocative test (EPT), 18 fulfilled diagnostic criteria for left ventricular apical ballooning syndrome (LVABS). EPT was negative in all these patients. On the other 328 patients, EPT was positive in 69 (21%). LVABS patients were more frequently women (94 vs. 30%), had a lower left ventricular ejection fraction (0.41 ± 0.11 vs. 0.55 ± 0.09), more troponin T level increments (83 vs. 23%), and a higher prevalence of stress situations (72 vs. 3%) than patients EPT positive.