David Calvo

Cardiac Fibrillation: From Ion Channels to Rotors in the Human Heart

Recent new information on the dynamics and molecular mechanisms of electrical rotors and spiral waves has increased our understanding of both atrial fibrillation and ventricular fibrillation. In this brief review, we evaluate the available evidence for the separate roles played by individual sarcolemmal ion channels in atrial fibrillation and ventricular fibrillation, assessing the clinical relevance of such findings. Importantly, although human data support the idea that rotors are a crucial mechanism for fibrillation maintenance in both atria and ventricles, there are clear inherent differences between the 2 chamber types, particularly in regard to the role of specific ion channels in fibrillation. But there also are similarities. This knowledge, together with new information on the changes that take place during disease evolution and between structurally normal and diseased hearts, may enhance our understanding of fibrillatory processes pointing to new approaches to improve disease outcomes.

Mechanisms of Fractionated Electrograms Formation in the Posterior Left Atrium During Paroxysmal Atrial Fibrillation in Humans

OBJECTIVES The aim of this paper was to study mechanisms of formation of fractionated electrograms on the posterior left atrial wall (PLAW) in human paroxysmal atrial fibrillation (AF). BACKGROUND The mechanisms responsible for complex fractionated atrial electrogram formation during AF are poorly understood. METHODS In 24 patients, we induced sustained AF by pacing from a pulmonary vein. We analyzed transitions between organized patterns and changes in electrogram morphology leading to fractionation in relation to interbeat interval duration (systolic interval [SI]) and dominant frequency. Computer simulations of rotors helped in the interpretation of the results. RESULTS Organized patterns were recorded 31 ± 18% of the time. In 47% of organized patterns, the electrograms and PLAW activation sequence were similar to those of incoming waves during pulmonary vein stimulation that induced AF. Transitions to fractionation were preceded by significant increases in electrogram duration, spike number, and SI shortening (R(2) = 0.94). Similarly, adenosine infusion during organized patterns caused significant SI shortening leading to fractionated electrograms formation. Activation maps during organization showed incoming wave patterns, with earliest activation located closest to the highest dominant frequency site. Activation maps during transitions to fragmentation showed areas of slowed conduction and unidirectional block. Simulations predicted that SI abbreviation that heralds fractionated electrograms formation might result from a Doppler effect on wave fronts preceding an approaching rotor or by acceleration of a stationary or meandering, remotely located source. CONCLUSIONS During induced AF, SI shortening after either drift or acceleration of a source results in intermittent fibrillatory conduction and formation of fractionated electrograms at the PLAW.

Atrial Septopulmonary Bundle of the Posterior Left Atrium Provides a Substrate for Atrial Fibrillation Initiation in a Model of Vagally Mediated Pulmonary Vein Tachycardia of the Structurally Normal Heart

Background— The posterior left atrium (PLA) and pulmonary veins (PVs) have been shown to be critical for atrial fibrillation (AF) initiation. However, the detailed mechanisms of reentry and AF initiation by PV impulses are poorly understood. We hypothesized that PV impulses trigger reentry and AF by undergoing wavebreaks as a result of sink-to-source mismatch at specific PV-PLA transitions along the septopulmonary bundle, where there are changes in thickness and fiber direction. Methods and Results— In 7 Langendorff-perfused sheep hearts AF was initiated by a burst of 6 pulses (CL 80 to 150ms) delivered to the left inferior or right superior PV ostium 100 to 150 ms after the sinus impulse in the presence of 0.5 &mgr;mol/L acetylcholine. The exposed septal-PLA endocardial area was mapped with high spatio-temporal resolution (DI-4-ANEPPS, 1000-fr/s) during AF initiation. Isochronal maps for each paced beat preceding AF onset were constructed to localize areas of conduction delay and block. Phase movies allowed the determination of the wavebreak sites at the onset of AF. Thereafter, the PLA myocardial wall thickness was quantified by echocardiography, and the fiber direction in the optical field of view was determined after peeling off the endocardium. Finally, isochrone, phase and conduction velocity maps were superimposed on the corresponding anatomic pictures for each of the 28 episodes of AF initiation. The longest delays of the paced PV impulses, as well as the first wavebreak, occurred at those boundaries along the septopulmonary bundle that showed sharp changes in fiber direction and the largest and most abrupt increase in myocardial thickness. Conclusion— Waves propagating from the PVs into the PLA originating from a simulated PV tachycardia triggered reentry and vagally mediated AF by breaking at boundaries along the septopulmonary bundle where abrupt changes in thickness and fiber direction resulted in sink-to-source mismatch and low safety for propagation.

The Atrial Septopulmonary Bundle of the Posterior Left Atrium Provides a Substrate for AF Initiation in a Model of Vagally Mediated Pulmonary Vein Tachycardia of the Structurally Normal Heart

Background— The posterior left atrium (PLA) and pulmonary veins (PVs) have been shown to be critical for atrial fibrillation (AF) initiation. However, the detailed mechanisms of reentry and AF initiation by PV impulses are poorly understood. We hypothesized that PV impulses trigger reentry and AF by undergoing wavebreaks as a result of sink-to-source mismatch at specific PV-PLA transitions along the septopulmonary bundle, where there are changes in thickness and fiber direction. Methods and Results— In 7 Langendorff-perfused sheep hearts AF was initiated by a burst of 6 pulses (CL 80 to 150ms) delivered to the left inferior or right superior PV ostium 100 to 150 ms after the sinus impulse in the presence of 0.5 &mgr;mol/L acetylcholine. The exposed septal-PLA endocardial area was mapped with high spatio-temporal resolution (DI-4-ANEPPS, 1000-fr/s) during AF initiation. Isochronal maps for each paced beat preceding AF onset were constructed to localize areas of conduction delay and block. Phase movies allowed the determination of the wavebreak sites at the onset of AF. Thereafter, the PLA myocardial wall thickness was quantified by echocardiography, and the fiber direction in the optical field of view was determined after peeling off the endocardium. Finally, isochrone, phase and conduction velocity maps were superimposed on the corresponding anatomic pictures for each of the 28 episodes of AF initiation. The longest delays of the paced PV impulses, as well as the first wavebreak, occurred at those boundaries along the septopulmonary bundle that showed sharp changes in fiber direction and the largest and most abrupt increase in myocardial thickness. Conclusion— Waves propagating from the PVs into the PLA originating from a simulated PV tachycardia triggered reentry and vagally mediated AF by breaking at boundaries along the septopulmonary bundle where abrupt changes in thickness and fiber direction resulted in sink-to-source mismatch and low safety for propagation.

Atrioventricular Conduction Disturbance Characterization in Transcatheter Aortic Valve Implantation With the CoreValve Prosthesis

Background— Atrioventricular (AV) block is one of the most frequent complications of CoreValve transcatheter aortic valve implantation (TAVI). The aim of this study was to analyze the effects of CoreValve implantation on AV conduction. Methods and Results— Electrophysiological study was performed immediately before and after CoreValve implantation in 18 consecutive, permanent pacemaker-free patients. An electrode was placed on the His bundle during valve implantation, and data were continuously recorded during the procedure. With surface ECG, a median (first, third quartile) QRS width of 96 (84, 116) to 150 (121, 164) ms (P=0.001) and PR interval of 180 (159, 216) to 210 (190, 240) ms (P=0.008) were significantly prolonged, and QRS axis was left deviated 30° (−32°, 46°) to −20° (−60°, 2°) (P=0.005). With intracardiac electrograms, the AH (97 [70, 123] to 115 [96, 135] ms, P=0.021) and HV (52 [42, 55] to 60 [50, 70] ms, P=0.002) intervals were increased. At the end of the procedure, we observed significant ECG- or electrophysiological study-persistent conduction disturbances in 14 (78%) patients. Five patients experienced transient changes (2 AV blocks and 3 left bundle branch blocks). Conclusions— CoreValve implantation worsens AV conduction in most patients, either transiently or permanently. This worsening is the result of direct damage either on the His bundle or on the AV node.

High-rate pacing-induced atrial fibrillation effectively reveals properties of spontaneously occurring paroxysmal atrial fibrillation in humans

AIMS Research on paroxysmal atrial fibrillation (AF) assumes that fibrillation induced by rapid pacing adequately reproduces spontaneously occurring paroxysmal AF in humans. We aimed to compare the spectral properties of spontaneous vs. induced AF episodes in paroxysmal AF patients. METHODS AND RESULTS Eighty-five paroxysmal AF patients arriving in sinus rhythm to the electrophysiology laboratory were evaluated prior to ablation. Atrial fibrillation was induced by rapid pacing from the pulmonary vein-left atrial junctions (PV-LAJ), the coronary sinus (CS), or the high right atrium (HRA). Simultaneous recordings were obtained using multipolar catheters. Off-line power spectral analysis of 5 s bipolar electrograms was used to determine dominant frequency (DF) at recording sites with regularity index >0.2. Sixty-eight episodes were analysed for DF. Comparisons were made between spontaneous (n = 23) and induced (n = 45) AF episodes at each recording site. No significant differences were observed between spontaneous and induced AF episodes in HRA (5.18 ± 0.69 vs. 5.06 ± 0.91 Hz; P = 0.64), CS (5.27 ± 0.69 vs. 5.36 ± 0.76 Hz; P = 0.69), or LA (5.72 ± 0.88 vs. 5.64 ± 0.75 Hz; P = 0.7) regardless of pacing site. Consistent with these results, paired analysis in seven patients with both spontaneous and induced AF episodes, showed no regional DFs differences. Moreover, a left-to-right DF gradient was also present in both spontaneous (PV-LAJ 5.71 ± 0.81 vs. HRA 5.18 ± 0.69 Hz; P = 0.005) and induced (PV-LAJ 5.62 ± 0.72 vs. HRA 5.07 ± 0.91 Hz; P = 0.002) AF episodes, with no differences between them (P = not specific). CONCLUSION In patients with paroxysmal AF, high-rate pacing-induced AF adequately mimics spontaneously initiated AF, regardless of induction site.

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).

KCNQ1 gene variants in the risk for type 2 diabetes and impaired renal function in the Spanish Renastur cohort

Several common KCNQ1 gene polymorphisms have been associated with the risk of type 2 diabetes (T2DM) and diabetic nephropathy. This effect is explained by the role of the kcnq1 protein as a potassium channel that in the pancreatic beta-cells drives an electrical signal that facilitates glucose-stimulated insulin secretion. The KCNQ1 gene is also expressed in the kidney, and could thus be implicated in the risk of developing impaired renal function. To test this hypothesis, we genotyped six common KCNQ1 gene variants (three single nucleotide polymorphisms, rs2237892, rs2237895, and rs231362, and three intronic indels) in 681 healthy elderly individuals (>65 years old) from the Spanish Renastur cohort. None of the six variants was associated with T2DM (180 diabetics vs. 581 non-diabetics). The intron 12 insertion allele was associated with a reduced estimated glomerular filtration rate (eGFR<60, n = 90 vs. eGFR≥60, n = 591; II vs ID + DD genotypes, p = 0.031, OR = 2.06, 95%CI = 1.12-4.14). We also performed a next generation sequencing search of variants in the coding regions of the KCNQ1 gene in 100 individuals with the extreme eGFR values. We found two rare amino acid changes (p.K393N and p.P408A) and the 393 Asn variant was found only among diabetics (n = 4; p = 0.05). The two rare alleles were present in the two eGFR groups. Our results suggest that a common KCNQ1 intron 12 indel polymorphism is a risk factor for impaired renal function independent of T2DM. If this association is confirmed by others, further research to determine the mechanism that drives this association would be warranted.

Bloqueo intrahisiano durante el implante de la prótesis aórtica percutánea CoreValve

1. Avanzas P, Muñoz-Garcı́a AJ, Segura J, Pan M, Alonso-Briales JH, Lozano I, et al. Implante percutáneo de la prótesis valvular aórtica autoexpandible CoreValve en pacientes con estenosis aórtica severa: experiencia inicial en España. Rev Esp Cardiol. 2010;63:141–8. 2. Al Ali AM, Altwegg L, Horlick EM, Feindel C, Thompson CR, Cheung A, et al. Prevention and management of transcatheter balloon expandable aortic valve malposition. Catheter Cardiovasc Interv. 2008;72:575–80. 3. Ussia GP, Mulè M, Tamburino C. The valve-in-valve technique: transcatheter treatment of aortic bioprothesis malposition. Catheter Cardiovasc Interv. 2009; 73:713–6. 4. Gerckens U, Latsios G, Mueller R, Buellesfeld L, John D, Yuecel S, et al. Procedural and mid-term results in patients with aortic stenosis treated with implantation of 2 (in-series) CoreValve prostheses in 1 procedure. JACC Cardiovasc Interv. 2010;3:244–50.

Prevalence of positive ECG criteria in young competitive athletes: a single region experience

We have read with great interest the article by Pellicia et al. about prevalence of abnormal ECG in a large, unselected population undergoing pre-participation cardiovascular screening and also read the Editorial by Corrado and Mckenna. As it is known, implementation of 12-lead ECG in the pre-participation screening programme has been a complex area of debate during years.1 Arguments against implementation of ECG as a routine exam …