QRS duration reflects underlying changes in conduction velocity during increased intraventricular pressure and heart failure.

Pressure overload and heart failure electrophysiological remodeling (HF-ER) in pigs are associated with decreased conduction velocity (CV) and dispersion of repolarization, which lead to higher risk of ventricular arrhythmia. This work aimed to establish the correlation between QRS complex duration and underlying changes in CV during increased intraventricular pressure (IVP) and/or HF-ER ex-vivo, and to determine whether QRS duration could be sensitive to an acute increase in left ventricular (LV) afterload in-vivo. HF-ER was induced in 7 pigs by high-rate ventricular pacing. Seven weight-matched animals were used as controls. Isolated Langendorff-perfused hearts underwent programmed ventricular stimulation to study QRS complex duration and CV under low/high IVP, using volume-conducted ECG and epicardial optical mapping, respectively. Four additional pigs underwent open-chest surgery to increase LV afterload by partially clamping the ascending aorta, while measuring QRS complex duration during sinus rhythm (SR). In 13 hearts included for analysis, both HF-ER and increased IVP showed significantly slower epicardial CV (-40% and -15%, p < 0.001 and p = 0.004, respectively), which correlated with similar widening of the QRS complex (+41% and +17%, p = 0.005 and p < 0.001, respectively). HF-ER hearts shower larger prolongation of the QRS complex than controls upon increasing the IVP (+21% vs. +12%, respectively. HF-ER*IVP interaction: p = 0.004). QRS complex widened after increasing LV afterload in-vivo (n=3), with correlation between QRS duration and aortic diastolic pressures (R = 0.58, p < 0.001). In conclusion, high IVP and/or HF-ER significantly decrease CV, which correlates with QRS widening on the ECG during ventricular pacing. Increased myocardial wall stress also widens the QRS complex during SR in-vivo.

Increased intraventricular pressures are as harmful as the electrophysiological substrate of heart failure in favoring sustained reentry in the swine heart.

BACKGROUND: Heart failure (HF) electrophysiological remodeling (HF-ER) often includes the effect of chronically increased intraventricular pressures (IVPs) and promotes ventricular tachycardia/ventricular fibrillation (VT/VF). In addition, acutely increased IVPs have been associated with a higher rate of VT/VF episodes in chronic HF. OBJECTIVE: We hypothesized that increased IVPs and/or an ionic-imbalanced (acidified), catecholamine-rich (adrenergic) milieu (AA milieu) may contribute as much as HF-ER to the substrate for reentry in HF. We used a porcine model of tachycardiomyopathy and evaluated the individual/combined contributions of (1) increased IVPs, (2) HF-ER, and (3) an AA milieu. METHODS: HF-ER was induced in 7 pigs by rapid pacing. Seven pigs were used as controls. Hearts were isolated and Langendorff perfused. Programmed ventricular stimulation was conducted under low or increased IVP and normal/AA milieu (4 combinations). Epicardial optical mapping was used to quantify conduction velocity (CV), action potential duration (APD), and dispersion of repolarization (DoR). RESULTS: HF-ER decreased CV (-34%; P = .002) and increased APD (11%; P = .024) and DoR (21%; P = .007). Increased IVP amplified DoR (36%; P < .001) and decreased CV (-17%; P = .001) and APD (-8%; P < .001). The AA milieu consistently modified only APD (-9%; P < .001) and led to amplified inter-/intra-subject heterogeneity. Increased IVP similarly raised the odds of inducing sustained VT/VF as the presence of HF-ER (>6-fold). CONCLUSION: By magnifying DoR, decreasing CV, and shortening APD, increased IVP was as harmful as HF-ER in favoring the substrate for sustained reentry in this model. The AA milieu contributed to a much lesser extent. Thus, a stricter control of IVP might be postulated as a useful add-on antiarrhythmic strategy in HF.

KATP channel opening accelerates and stabilizes rotors in a swine heart model of ventricular fibrillation.

AIMS: The mechanisms underlying ventricular fibrillation (VF) are still disputed. Recent studies have highlighted the role of KATP-channels. We hypothesized that, under certain conditions, VF can be driven by stable and epicardially detectable rotors in large hearts. To test our hypothesis, we used a swine model of accelerated VF by opening KATP-channels with cromakalim. METHODS AND RESULTS: Optical mapping, spectral analysis, and phase singularity tracking were performed in eight perfused swine hearts during VF. Pseudo-bipolar electrograms were computed. KATP-channel opening almost doubled the maximum dominant frequency (14.3 ± 2.2 vs. 26.5 ± 2.8 Hz, P < 0.001) and increased the maximum regularity index (0.82 ± 0.05 vs. 0.94 ± 0.04, P < 0.001), the density of rotors (2.0 ± 1.4 vs. 16.0 ± 7.0 rotors/cm²×s, P < 0.001), and their maximum lifespans (medians: 368 vs. ≥3410 ms, P < 0.001). Persistent rotors (≥1 movie = 3410 ms) were found in all hearts after cromakalim (mostly coinciding with the fastest and highest organized areas), but they were not epicardially visible at baseline VF. A 'beat phenomenon' ruled by inter-domain frequency gradients was observed in all hearts after cromakalim. Acceleration of VF did not reveal any significant regional preponderance. Complex fractionated electrograms were not found in areas near persistent rotors. CONCLUSION: Upon KATP-channel opening, VF consisted of rapid and highly organized domains mainly due to stationary rotors, surrounded by poorly organized areas. A 'beat phenomenon' due to the quasi-periodic onset of drifting rotors was observed. These findings demonstrate the feasibility of a VF driven by stable rotors in hearts whose size is similar to the human heart. Our model also showed that complex fractionation does not seem to localize stationary rotors.

Skeletal myoblast implants induce minor propagation delays, but do not promote arrhythmias in the normal swine heart.

AIMS: Whether skeletal myoblast (SM) implants are proarrhythmic is still controversial due to conflicting pre-clinical and clinical data. We hypothesized that if SM implants are arrhythmogenic, they will facilitate the induction of ventricular tachyarrhythmias by promoting heterogeneous propagation of activation wavefronts. METHODS: Skeletal myoblast cells were harvested from 10 pigs. A month later, 125 ± 37 × 10(6) cells were subepicardially injected in an area of ∼2 cm(2) at the anterolateral aspect of the left ventricle. Four weeks later, a ventricular stimulation protocol was conducted. Once explanted, epicardial wavefronts over SM and adjacent control areas were optically mapped. Eight saline-injected animals were used as controls. To compare with clear arrhythmogenic substrates, propagation patterns were also evaluated in infarcted hearts and on a SM-implanted heart following amiodarone infusion. RESULTS: In SM hearts, fibrosis and differentiated SM cells were consistently found and no tachyarrhythmias were induced. Wavefronts propagated homogeneously over SM and adjacent areas, with no late activation zones, as opposed to the infarcted hearts. The time required for the wavefronts to depolarize both areas were similar, becoming only slightly longer at SM areas after an extra-stimulus (P = 0.025). Conduction velocities and APD(90) were also similar. Saline hearts showed similar results. The extent of the conduction delay was not related to the number of injected SM cells. CONCLUSION: In normal swine hearts, myoblast implants promote localized fibrosis and slightly retard epicardial wavefront propagation only after extra-stimuli. However, SM implants are not associated with local re-entry and do not facilitate ventricular tachyarrhythmias in the whole normal heart.

La ablación de taquicardia intranodal con sistema de navegación remota Stereotaxis® precisa menores parámetros de temperatura y potencia por mejoría del contacto tisular / Ablation of atrioventricular nodal reentrant tachycardia using remote magnetic guidance (Stereotaxis®) requires lower temperature and power settings because of improved local contact

Introducción y objetivos. La navegación magnética remota con sistema Stereotaxis® supone una nueva forma de ablación que podría aumentar la estabilidad del catéter. Quisimos evaluar si la posible mejoría del contacto tisular obliga a modificar los parámetros convencionales de radiofrecuencia. Métodos. Se comparó a 19 pacientes sometidos a ablación de taquicardia intranodal con catéter remoto de 4 mm con 18 pacientes con procedimiento convencional (4 mm, 60-65 °C, 50 W). Evaluamos la energía de radiofrecuencia necesaria para conseguir la no inducibilidad de más de un eco nodal. Resultados. El primer catéter remoto presentó carbonización tras las primeras aplicaciones con parámetros habituales. Así, redujimos la energía (50 °C, 40 W) en el resto. No hubo diferencias en número de aplicaciones entre grupo remoto y control (mediana, 6 [rango intercuartílico, 11] frente a 8,5 [9]). Aplicaciones ≤ 5 s suelen deberse a desplazamiento del catéter. Sólo 4 pacientes del grupo remoto tuvieron aplicaciones ≤ 5 s frente a 11 controles (p = 0,041). La ablación remota fue igual de efectiva, y se realizó con menores temperaturas y potencias medias (media ± DE, 46 ± 2 frente a 50 ± 4 °C; p < 0,001; y 29 [14] frente a 50 [7] W; p < 0,001), pero sin diferencias en energía total aplicada. Con el catéter remoto se registró menor amplitud de impedancias entre aplicaciones (media ± DE, 10,4 ± 7,6 frente a 19,3 ± 15,4 Ω; p = 0,035) y una tendencia a menor amplitud de temperaturas, lo que indica más estabilidad entre aplicaciones. No se produjeron complicaciones. Conclusiones. En nuestra serie inicial, el uso de navegación remota en la ablación de taquicardia intranodal fue efectiva y segura. La mejoría del contacto tisular disminuye desplazamientos involuntarios del catéter y parece que se necesita disminuir la potencia de radiofrecuencia para evitar la carbonización del catéter (AU)

Introduction and objectives. The Stereotaxis® remote magnetic navigation system provides a new approach to ablation that could increase catheter stability. The aim was to determine whether improved tissue contact necessitates a change in traditional radiofrequency ablation parameters. Methods. The study compared ablation of atrioventricular nodal reentrant tachycardia (AVNRT) using remote navigation (4-mm catheter) in 19 patients with conventional ablation in 18 patients (4-mm catheter, temperature 60-65oC, power 50 W). The radiofrequency energy needed to ensure that no more than a single nodal echo beat could be induced was measured. Results. Charring was observed with traditional parameters on the first applications of the remotely navigated catheter. Hence, the energy was subsequently reduced (to 50oC and 40 W). There was no difference in the number of applications between remote navigation and conventional groups (median: 6 vs 8.5; interquartile range [IQR]: 11 vs 9). Applications lasting ≤5 s were usually due to catheter dislodgment. Only 4 patients in the remote group had applications ≤5 s compared with 11 in the conventional group (P=.041). Ablation using remote navigation was equally effective and required lower temperatures and powers (mean [SD] temperature: 46 oC (2oC) vs 50oC (4oC), P < .001; median [IQR] power: 29 [14] W vs 50 [7] W, P < .001), with no difference in total energy delivered. With remote navigation, the range of impedance values between applications was less (mean [SD]: 10.4 [7.6] ¿ vs 19.3 [15.4] ¿; P=.035) and the temperature variation tended to be less, suggesting greater stability between applications. There were no complications. Conclusions. In this initial series, remote magnetic navigation was safe and effective in AVNRT ablation. Improved tissue contact reduced catheter dislodgment and necessitated a reduction in radiofrequency energy to avoid charring (AU)

Ablation of atrioventricular nodal reentrant tachycardia using remote magnetic guidance (stereotaxis) requires lower temperature and power settings because of improved local contact.

INTRODUCTION AND OBJECTIVES: The Stereotaxis(R) remote magnetic navigation system provides a new approach to ablation that could increase catheter stability. The aim was to determine whether improved tissue contact necessitates a change in traditional radiofrequency ablation parameters. METHODS: The study compared ablation of atrioventricular nodal reentrant tachycardia (AVNRT) using remote navigation (4-mm catheter) in 19 patients with conventional ablation in 18 patients (4-mm catheter, temperature 60-65 degrees C, power 50 W). The radiofrequency energy needed to ensure that no more than a single nodal echo beat could be induced was measured. RESULTS: Charring was observed with traditional parameters on the first applications of the remotely navigated catheter. Hence, the energy was subsequently reduced (to 50 degrees C and 40 W). There was no difference in the number of applications between remote navigation and conventional groups (median: 6 vs. 8.5; interquartile range [IQR]: 11 vs. 9). Applications lasting

Improving adjunctive treatment in pulmonary embolism and fibrinolytic therapy. The role of enoxaparin and weight-adjusted unfractionated heparin.

AIM: The role of enoxaparin and weight-adjusted unfractionated heparin (UH) as adjunct to fibrinolytic therapy in pulmonary embolism is unknown. METHODS: In a prospective, open-label, controlled multicenter trial, 80 patients with high-risk pulmonary embolism were enrolled. Forty patients received alteplase infusion plus weight-adjusted UH (24-48 h) and then enoxaparin (7 days). In control group, UH standard regimen was used. There were not differences on pulmonary embolism extension, (P 0.63) and right ventricular hypokinesis (P 0.07) in both groups. In terms of in-hospital survival (P 0.009), escalation treatment (P < 0.001) and in-hospital stay (P < 0.001) study group had better outcome than opposite group. In a 30 (P < 0.001) and 90 (P < 0.001) days follow-up pulmonary perfusion was improved in patients who received enoxaparin versus heparin alone without increasing major bleeding complications. CONCLUSION: Enoxaparin and weight-adjusted intravenous UH as adjunct to 1-h alteplase infusion improve in-hospital and follow-up outcome compared to heparin alone in high-risk PE.

Marcadores hemostáticos y de inflamación en síndromes coronarios agudos y su asociación con eventos cardiovasculares adversos / Haemostatic and inflammation markers in acute coronary syndromes and its relationship with adverse cardiovascular events

BACKGROUND: In acute coronary syndromes (ACS) interaction among several haemostatic (S and C protein, antitrhombin Ill, C protein resistance, plasminogen, alpha 2-antiplasmi and inflammatory factors (white cell blood count, fibrinogen, reactive C protein) could have association with recurrent thrombosis and recurrence ischemia, reinfarction, shock and cardiovascular mortality. METHODS: Prospective, controlled, with a six-year follow-up trial. END-POINT: Prove in acute phase and in a follow-up association among inflammatory, coagulation and fibrinolysis markers with cardiovascular adverse events. INCLUSION: a) ischemic chest pain at rest > 20 minutes with ST depression or elevation ACS, b) clinical stability. EXCLUSION: a) > 75 years-old, b) ACS secondary stress, hypertensive crisis, aortic stenosis, c) another acute vascular syndromes suggesting acute ischemia, d) Killip and Kimbal III o IV, e) ejection fraction < 35%, f) pre-hospital treatment with any medication that modify coagulation or fibrinolysis, c) inflammatory acute or chronic process. CONTROL GROUPS: Healthy individuals and stable chronic heart disease patients whose were matched by age and sex. In all patients with ischemic heart disease angiography, nuclear medicine or echocardiography stress tests were done. STATISTICS: Chi square, student t-test. Lineal, logistic and multivariate regression. Kaplan-Meier and Cox survival curves. Statistical significance: p < 0.05. RESULTS: 50 patients with non- or ST elevation ACS were enrolled. Regression logistic analysis indicated association among plasminogen, antithrombin III and C reactive-protein (p < 0.00001) with death. Protein C and S, protein C resistance and antithrombin III had correlation with death (p 0.0001) and recurrent ischemia (p < 0.0001). Multivariate analysis showed that antithrombin III, plasminogen, C reactive-protein and fibrinogen had significant correlation with death (p 0.001), cardiogenic shock (0.001), new ST-elevation myocardial infarction (0.001). CONCLUSION: These findings suggesting that in acute phase and in a follow-up of an ACS abnormal coagulation, inflammation and fibrinolysis markers had independent and direct relationship with cardiovascular adverse events.

[Haemostatic and inflammation markers in acute coronary syndromes and its relationship with adverse cardiovascular events]. / Marcadores hemostáticos y de inflamación en síndromes coronarios agudos y su asociación con eventos cardiovasculares adversos.

BACKGROUND: In acute coronary syndromes (ACS) interaction among several haemostatic (S and C protein, antitrhombin Ill, C protein resistance, plasminogen, alpha 2-antiplasmi and inflammatory factors (white cell blood count, fibrinogen, reactive C protein) could have association with recurrent thrombosis and recurrence ischemia, reinfarction, shock and cardiovascular mortality. METHODS: Prospective, controlled, with a six-year follow-up trial. END-POINT: Prove in acute phase and in a follow-up association among inflammatory, coagulation and fibrinolysis markers with cardiovascular adverse events. INCLUSION: a) ischemic chest pain at rest > 20 minutes with ST depression or elevation ACS, b) clinical stability. EXCLUSION: a) > 75 years-old, b) ACS secondary stress, hypertensive crisis, aortic stenosis, c) another acute vascular syndromes suggesting acute ischemia, d) Killip and Kimbal III o IV, e) ejection fraction < 35%, f) pre-hospital treatment with any medication that modify coagulation or fibrinolysis, c) inflammatory acute or chronic process. CONTROL GROUPS: Healthy individuals and stable chronic heart disease patients whose were matched by age and sex. In all patients with ischemic heart disease angiography, nuclear medicine or echocardiography stress tests were done. STATISTICS: Chi square, student t-test. Lineal, logistic and multivariate regression. Kaplan-Meier and Cox survival curves. Statistical significance: p < 0.05. RESULTS: 50 patients with non- or ST elevation ACS were enrolled. Regression logistic analysis indicated association among plasminogen, antithrombin III and C reactive-protein (p < 0.00001) with death. Protein C and S, protein C resistance and antithrombin III had correlation with death (p 0.0001) and recurrent ischemia (p < 0.0001). Multivariate analysis showed that antithrombin III, plasminogen, C reactive-protein and fibrinogen had significant correlation with death (p 0.001), cardiogenic shock (0.001), new ST-elevation myocardial infarction (0.001). CONCLUSION: These findings suggesting that in acute phase and in a follow-up of an ACS abnormal coagulation, inflammation and fibrinolysis markers had independent and direct relationship with cardiovascular adverse events.