Mejoría clínica, hemodinámica y de marcadores bioquímicos tras estimulación ventricular desde el área de la rama izquierda / Clinical, hemodynamic and biochemical improvement related to left bundle branch area pacing

Resumen Introducción: La estimulación ventricular derecha puede provocar insuficiencia cardiaca y disfunción ventricular. La estimulación en el área de la rama izquierda (ERI) permite capturar el sistema His-Purkinje. La ERI se ha estudiado en la estimulación ventricular y en la terapia de resincronización cardiaca. La evolución de los péptidos natriuréticos (NT-proBNP) asociada a la ERI no ha sido estudiada hasta el momento. Métodos: Se incluyeron pacientes consecutivos remitidos para implante de marcapasos o terapia de resincronización cardiaca. El implante del electrodo de ERI se realizó siguiendo la técnica descrita por Huang et al. Los pacientes eran sometidos a ecocardiograma y determinación de NT-proBNP antes y cuatro semanas después del procedimiento. Resultados: Se analizaron 50 pacientes con implante exitoso y seguimiento completo. No hubo diferencias significativas entre los umbrales medidos durante el procedimiento y los obtenidos al cabo de 12 semanas. La ERI logró una reducción significativa de la anchura del complejo QRS (148 ± 21 vs. 107 ± 11 ms; p = 0.029). La ERI logró una reducción significativa de la clasificación funcional en el conjunto de la muestra y una reducción significativa de NT-proBNP (2,888.2 ± 510 vs. 1,181 ± 130 pg/ml; p = 0.04). En pacientes con fracción de eyección del ventrículo izquierdo (FEVI) < 50% y asincronía se logró un incremento significativo de la FEVI con la ERI (40.2 ± 7 vs. 55.2 ± 7%; p < 0.001). Conclusiones: La ERI es factible en la mayoría de pacientes y se asocia con una reducción de la duración del complejo QRS. La ERI no condiciona un efecto deletéreo sobre la FEVI a corto-medio plazo; además, en aquellos pacientes con FEVI deprimida y asincronía ventricular permite incrementar la FEVI.

Abstract Background: Right ventricular pacing is associated with risk of heart failure and left ventricular dysfunction. Left bundle branch area pacing (LBBP) has emerged as an alternative method for delivering physiological pacing. The effect of LBBP on N-terminal pro-brain natriuretic peptide (NT-proBNP) has not been investigated. Method: Finally, 50 patients referred for pacemaker implantation were included. LBBP was performed as described previously by Huang et al. Transthoracic echocardiogram and NT-proBNP were performed before and four weeks after the procedure. Results: 50 patients were analyzed. There were not differences between ventricular thresholds during the procedure and 3 months later, LBBP significantly reduced QRS complex duration (148 ± 21 vs. 107 ± 11 ms; p = 0.029). LBBP significantly improved NYHA functional class and reduced NT-proBNP concentration (2888.2 ± 510 vs. 1181 ± 130 pg/ml; p = 0.04). In patients showing left ventricular ejection fraction (LVEF) < 50% and ventricular desynchrony LBBP showed a significant LVEF increase (40.2 ± 7 vs. 55.2 ± 7%; p < 0.001). Conclusions: LBBP was feasible and safe in most of patients. LBBP was associated with reduction in QRS width and with increase in LVEF in patients with ventricular desynchrony, while in patients with normal LVEF it remained unchanged during follow-up.

Clinical, hemodynamic and biochemical improvement related to left bundle branch area pacing.

BACKGROUND: Right ventricular pacing is associated with risk of heart failure and left ventricular dysfunction. Left bundle branch area pacing (LBBP) has emerged as an alternative method for delivering physiological pacing. The effect of LBBP on N-terminal pro-brain natriuretic peptide (NT-proBNP) has not been investigated. METHOD: Finally, 50 patients referred for pacemaker implantation were included. LBBP was performed as described previously by Huang et al. Transthoracic echocardiogram and NT-proBNP were performed before and four weeks after the procedure. RESULTS: 50 patients were analyzed. There were not differences between ventricular thresholds during the procedure and 3 months later, LBBP significantly reduced QRS complex duration (148 ± 21 vs. 107 ± 11 ms; p = 0.029). LBBP significantly improved NYHA functional class and reduced NT-proBNP concentration (2888.2 ± 510 vs. 1181 ± 130 pg/ml; p = 0.04). In patients showing left ventricular ejection fraction (LVEF) < 50% and ventricular desynchrony LBBP showed a significant LVEF increase (40.2 ± 7 vs. 55.2 ± 7%; p < 0.001). CONCLUSIONS: LBBP was feasible and safe in most of patients. LBBP was associated with reduction in QRS width and with increase in LVEF in patients with ventricular desynchrony, while in patients with normal LVEF it remained unchanged during follow-up.

INTRODUCCIÓN: La estimulación ventricular derecha puede provocar insuficiencia cardiaca y disfunción ventricular. La estimulación en el área de la rama izquierda (ERI) permite capturar el sistema His-Purkinje. La ERI se ha estudiado en la estimulación ventricular y en la terapia de resincronización cardiaca. La evolución de los péptidos natriuréticos (NT-proBNP) asociada a la ERI no ha sido estudiada hasta el momento. MÉTODOS: Se incluyeron pacientes consecutivos remitidos para implante de marcapasos o terapia de resincronización cardiaca. El implante del electrodo de ERI se realizó siguiendo la técnica descrita por Huang et al. Los pacientes eran sometidos a ecocardiograma y determinación de NT-proBNP antes y cuatro semanas después del procedimiento. RESULTADOS: Se analizaron 50 pacientes con implante exitoso y seguimiento completo. No hubo diferencias significativas entre los umbrales medidos durante el procedimiento y los obtenidos al cabo de 12 semanas. La ERI logró una reducción significativa de la anchura del complejo QRS (148 ± 21 vs. 107 ± 11 ms; p = 0.029). La ERI logró una reducción significativa de la clasificación funcional en el conjunto de la muestra y una reducción significativa de NT-proBNP (2,888.2 ± 510 vs. 1,181 ± 130 pg/ml; p = 0.04). En pacientes con fracción de eyección del ventrículo izquierdo (FEVI) < 50% y asincronía se logró un incremento significativo de la FEVI con la ERI (40.2 ± 7 vs. 55.2 ± 7%; p < 0.001). CONCLUSIONES: La ERI es factible en la mayoría de pacientes y se asocia con una reducción de la duración del complejo QRS. La ERI no condiciona un efecto deletéreo sobre la FEVI a corto-medio plazo; además, en aquellos pacientes con FEVI deprimida y asincronía ventricular permite incrementar la FEVI.

Vasodilator Stress CMR and All-Cause Mortality in Stable Ischemic Heart Disease: A Large Retrospective Registry.

OBJECTIVES: This study explored the association of ischemic burden, as measured by vasodilator stress cardiovascular magnetic resonance (CMR), with all-cause mortality and the effect of revascularization on all-cause mortality in patients with stable ischemic heart disease (SIHD). BACKGROUND: In patients with SIHD, the association of ischemic burden, derived from vasodilator stress CMR, with all-cause mortality and its role for decision-making is unclear. METHODS: The registry consisted of 6,389 consecutive patients (mean age: 65 ± 12 years; 38% women) who underwent vasodilator stress CMR for known or suspected SIHD. The ischemic burden (at stress first-pass perfusion imaging) was computed (17-segment model). The effect of CMR-related revascularization (within the following 3 months) on all-cause mortality was retrospectively explored using the electronic regional health system registry. RESULTS: During a 5.75-year median follow-up, 717 (11%) deaths were documented. In multivariable analyses, more extensive ischemic burden (per 1-segment increase) was independently related to all-cause mortality (hazard ratio: 1.04; 95% confidence interval: 1.02 to 1.07; p < 0.001). In 1,032 1:1 matched patients using a limited number of variables (516 revascularized, 516 non-revascularized), revascularization within the following 3 months was associated with less all-cause mortality only in patients with extensive CMR-related ischemia (>5 segments, n = 432; 10% vs. 24%; p = 0.01). CONCLUSIONS: In a large retrospective registry of unselected patients with known or suspected SIHD who underwent vasodilator stress CMR, extensive ischemic burden was related to a higher risk of long-term, all-cause mortality. Revascularization was associated with a protective effect only in the restricted subset of patients with extensive CMR-related ischemia. Further research will be needed to confirm this hypothesis-generating finding.

Complex left main coronary stent restenosis treated through radial approach using a sheathless catheter.

A 64-year-old woman was admitted for non-ST elevation myocardial infarction. The coronary angiogram showed a severe stenosis in the left anterior descending artery (LAD) ostium. A 3.5 mm×18 mm everolimus-eluting stent was directly deployed in the left main and proximal LAD, with significant jailing of the circumflex (Cx) ostium. A 3.25 mm×11 mm everolimus-eluting stent was therefore deployed in the Cx using the T-stenting and small protrusion technique. One year later, the patient was readmitted for non-ST elevation myocardial infarction, and the coronary angiogram showed ostial restenosis of the Cx stent. Optical coherence tomography imaging confirmed the severity of ostial restenosis. Percutaneous coronary intervention by a radial approach was performed using a sheathless guide catheter.

Usefulness of delta troponin for diagnosis and prognosis assessment of non-ST-segment elevation acute chest pain.

BACKGROUND: The additional diagnostic and prognostic information provided by delta high-sensitivity troponin T (hs-cTnT) in patients with acute chest pain and hs-cTnT elevation remains unclear. METHODS: The study group consisted of 601 patients presenting at the emergency department with non-ST-segment elevation acute chest pain and hs-cTnT elevation after two determinations (admission and within the first six hours). Maximum hs-cTnT and delta hs-cTnT (absolute or percentage change between the two measurements) were considered. Cutoff values were optimized using the quartile distribution for the endpoints. The endpoints were diagnostic (significant stenosis in the coronary angiogram) and prognostic (death or recurrent myocardial infarction at one year). RESULTS: Regarding the diagnostic endpoint, 114 patients showed a normal angiogram. Both maximum hs-cTnT ⩾80 ng/ml (OR 2.5, 95% CI 1.3-4.8, P=0.005) and delta hs-cTnT ⩾20 ng/l (OR 2.1, 95% CI 1.1-4.0, P=0.02) median value cutoffs were related to significant coronary stenosis. Furthermore, the combination of hs-cTn <80 ng/l and delta hs-cTn <20 ng/l showed the lowest probability of significant coronary stenosis (OR 0.3, 95% CI 0.1-0.4, P=0.001). During follow-up, 86 patients experienced the prognostic endpoint. After full adjustment for clinical data, maximum hs-cTnT ⩾30 ng/l, first quartile cutoff, was related to the outcome (HR 1.8, 95% CI 1.0-3.4, P=0.05), while delta hs-cTnT, either absolute or percentage change, lacked prognostic value. CONCLUSIONS: Maximum hs-cTnT captures all the prognostic information provided by hs-cTnT in non-ST-segment elevation acute chest pain. Low maximum and low delta hs-cTnT are associated with a normal coronary angiogram, which could make the final diagnosis challenging in some cases.

Usefulness of Clinical Data and Biomarkers for the Identification of Frailty After Acute Coronary Syndromes.

BACKGROUND: Frailty predicts mortality after acute coronary syndrome (ACS). The standard frailty scales, such as the Fried score, consist of a variety of questionnaires and physical tests. Our aim was to investigate easily available clinical data and blood markers to predict frailty at discharge, in elderly patients after ACS. METHODS: A total of 342 patients older than 65 years, survivors after ACS, were included. A high number of clinical variables were collected. In addition, blood markers potentially linked to frailty and related to the processes of inflammation, coagulation, hormonal dysregulation, nutrition, renal dysfunction, and heart dysfunction were determined. Frailty was evaluated using the Fried score at discharge. The main outcome was frailty defined by a Fried score ≥ 3 points. Secondary endpoints were mortality and myocardial infarction at 30-month median follow-up. RESULTS: A total of 116 patients were frail. Seven clinical variables or biomarkers predicted frailty: age ≥ 75 years, female, prior ischemic heart disease, admission heart failure, haemoglobin ≤ 12.5 g/dL, vitamin D ≤ 9 ng/mL, and cystatin-C ≥ 1.2 mg/L. This model based on clinical data and biomarkers showed an excellent discrimination accuracy for frailty (C-statistic = 0.818). During the follow-up, 105 patients died and 137 died or suffered myocardial infarction. The clinical data and biomarker model (C-statistics = 0.730 and 0.691) performed better than the Fried score (C-statistics = 0.676 and 0.650) for death and death or myocardial infarction, respectively. CONCLUSIONS: Easy available clinical data and biomarkers can identify frail patients at discharge after ACS and predict outcomes better than the standard Fried's frailty scale.

Prognostic value of the interaction between galectin-3 and antigen carbohydrate 125 in acute heart failure.

AIMS: Galectin-3 (Gal-3) and carbohydrate antigen 125 (CA125) have emerged as robust prognostic biomarkers in heart failure. Experimental data have also suggested a potential molecular interaction between CA125 and Gal-3; however, the biological and clinical relevance of this interaction is still uncertain. We sought to evaluate, in patients admitted for acute heart failure, the association between plasma Gal-3 with all-cause mortality and the risk for rehospitalizations among high and low levels of CA125. METHODS AND RESULTS: We included 264 consecutive patients admitted for acute heart failure to the Cardiology Department in a third-level center. Both biomarkers were measured on admission. Negative binomial and Cox regression models were used to evaluate the prognostic effect of the interaction between Gal-3 and CA125 (dichotomized by its median) with hospital readmission and all-cause mortality, respectively. During a median follow-up of 2 years (IQR = 1-2.8), 108 (40.9%) patients deaths and 365 rehospitalizations in 171 (69.5%) patients were registered. In a multivariable setting, the effect of Gal-3 on mortality and rehospitalization was differentially mediated by CA125 (p = 0.007 and p<0.001, respectively). Indeed, in patients with CA125 above median (>67 U/ml), values across the continuum of Gal-3 showed a positive and almost linear relationship with either the risk of death or rehospitalization. Conversely, when CA125 was below median (≤67 U/ml), Gal-3 lacked any prognostic effect on both endpoints. CONCLUSION: In patients with acute heart failure, Gal-3 was strongly associated with higher risk of long-term mortality and repeated rehospitalizations, but only in those patients exhibiting higher values of CA125 (above 67 U/ml).

Usefulness and safety of a guide catheter extension system for the percutaneous treatment of complex coronary lesions by a transradial approach.

OBJECTIVE: The aim of this study was to describe our initial experience with the GuideLiner® catheter (Vascular Solutions Inc.) in the transradial treatment of complex lesions. MATERIALS AND METHODS: The clinical, angiographic and procedural data of percutaneous coronary interventions where GuideLiner was used during 2013 were collected. The transradial approach was used in all cases. The indication for its use, efficacy and periprocedural complications were determined. Sixteen consecutive procedures (in 15 patients; 12 males and 3 females) were evaluated. The indication for the use of GuideLiner was a difficulty to advance and properly position a stent through a tortuous and/or calcified artery despite using high-support guide catheters or other useful techniques. RESULTS: Of the 16 angiographic procedures, 14 (87.5%) were successful (stent deployment in 13 cases and a drug-eluting balloon in 1 case). Unsuccessful cases were a chronic total occlusion and a diffusely diseased left anterior descendant artery. A type B dissection of a proximal left circumflex artery was the only periprocedural complication. CONCLUSION: Use of the GuideLiner was an effective and safe technique for the percutaneous treatment of complex coronary lesions in which the adequate progress of angioplasty devices had failed. GuideLiner was particularly helpful when using the transradial approach. Only one minor complication was recorded.

Frailty and other geriatric conditions for risk stratification of older patients with acute coronary syndrome.

BACKGROUND: Geriatric conditions may predict outcomes beyond age and standard risk factors. Our aim was to investigate a wide spectrum of geriatric conditions in survivors after an acute coronary syndrome. METHODS: A total of 342 patients older than 65 years were included. At hospital discharge, 5 geriatric conditions were evaluated: frailty (Fried and Green scores), physical disability (Barthel index), instrumental disability (Lawton-Brody scale), cognitive impairment (Pfeiffer questionnaire), and comorbidity (Charlson and simple comorbidity indexes). The outcomes were postdischarge mortality and the composite of death/myocardial infarction during a 30-month median follow-up. RESULTS: Seventy-four (22%) patients died and 105 (31%) suffered from the composite end point. Through univariable analysis, all individual geriatric indexes were associated with outcomes, mainly mortality. Of all of them, frailty using the Green score had the strongest discriminative accuracy (area under the receiver operating characteristic curve 0.76 for mortality). After full adjustment including clinical and geriatric data, the Green score was the only independent predictive geriatric condition (per point; mortality: hazard ratio 1.25, 95% CI 1.15-1.36, P = .0001; composite end point: hazard ratio 1.16, 95% CI 1.09-1.24, P = .0001). A Green score ≥ 5 points was the strongest mortality predictor. The addition of the Green score to the clinical model improved discrimination (area under the receiver operating characteristic curve 0.823 vs 0.846) and significantly reclassified mortality risk (net reclassification improvement 26.3, 95% CI 1.4-43.5; integrated discrimination improvement 4.0, 95% CI 0.8-9.0). The incremental predictive information was even greater over the GRACE score. CONCLUSIONS: Frailty captures most of the prognostic information provided by geriatric conditions after acute coronary syndromes. The Green score performed better than the other geriatric indexes.

High-sensitivity versus conventional troponin for management and prognosis assessment of patients with acute chest pain.

OBJECTIVES: High-sensitivity troponin (hs-cTn) is substituting conventional cTn for evaluation of chest pain. Our aim was to assess the impact on patient management and outcome. METHODS: A total of 1372 consecutive patients presenting at the emergency department with non-ST-elevation acute chest pain were divided into two periods according to the cTn assay used, conventional (n=699, March 2008 to July 2010) or hs-cTn (n=673, November 2010 to March 2013). Management policies were similar and according to guidelines. The primary endpoint was major adverse cardiac events (MACE) at 6 months (death, myocardial infarction, readmission by unstable angina or postdischarge revascularisation). RESULTS: There were minor differences in baseline characteristics. In the hs-cTn period, more patients elevated cTn (73% vs 37%, p=0.0001) leading to more coronary angiograms (77% vs 55%, p=0.0001) and revascularisations (45% vs 31%, p=0.0001); conversely, fewer patients were initially assigned to exercise testing (14% vs 36%, p=0.0001) and, therefore, discharged early after a negative result (7% vs 22%, p=0.0001). At 6 months, 135 patients suffered MACE, including 54 deaths. After adjusting for a Propensity Score, hs-cTn use was not significantly associated with MACE (HR=0.99; 95% CI 0.70 to 1.41; p=0.98) or mortality (HR=1.02; 95% CI 0.59 to 1.77; p=0.95), though the risk of longer hospitalisation stay increased at the index episode (OR=1.35, 95% CI 1.07 to 1.71, p=0.02). CONCLUSIONS: hs-cTn simplified chest pain triage on avoiding a more complex evaluation with non-invasive tests in the chest pain unit, but prompted longer hospitalisations and more invasive procedures without impacting on the 6-month outcomes.

Effect of ischemic postconditioning on microvascular obstruction in reperfused myocardial infarction. Results of a randomized study in patients and of an experimental model in swine.

BACKGROUND: Ischemic postconditioning (PCON) appears as a potentially beneficial tool in ST-segment elevation myocardial infarction (STEMI). We evaluated the effect of PCON on microvascular obstruction (MVO) in STEMI patients and in an experimental swine model. METHODS: A prospective randomized study in patients and an experimental study in swine were carried out in two university hospitals in Spain. 101 consecutive STEMI patients were randomized to undergo primary angioplasty followed by PCON or primary angioplasty alone (non-PCON). Using late gadolinium enhancement cardiovascular magnetic resonance, infarct size and MVO were quantified (% of left ventricular mass). In swine, using an angioplasty balloon-induced anterior STEMI model, MVO was defined as the % of area at risk without thioflavin-S staining. RESULTS: In patients, PCON (n=49) in comparison with non-PCON (n=52) did not significantly reduce MVO (0 [0-1.02]% vs. 0 [0-2.1]% p=0.2) or IS (18 ± 13% vs. 21 ± 14%, p=0.2). MVO (>1 segment in the 17-segment model) occurred in 12/49 (25%) PCON and in 18/52 (35%) non-PCON patients, p=0.3. No significant differences were observed between PCON and non-PCON patients in left ventricular volumes, ejection fraction or the extent of hemorrhage. In the swine model, MVO occurred in 4/6 (67%) PCON and in 4/6 (67%) non-PCON pigs, p=0.9. The extent of MVO (10 ± 7% vs. 10 ± 8%, p=0.9) and infarct size (23 ± 14% vs. 24 ± 10%, p=0.8) was not reduced in PCON compared with non-PCON pigs. CONCLUSIONS: Ischemic postconditioning does not significantly reduce microvascular obstruction in ST-segment elevation myocardial infarction. Clinical Trial Registration http://www.clinicaltrials.gov. Unique identifier: NCT01898546.

Microvascular obstruction in the right ventricle in reperfused anterior myocardial infarction. Macroscopic and pathologic evidence in a swine model.

INTRODUCTION: Data on right ventricular (RV) involvement in anterior myocardial infarction are scarce. The presence of RV microvascular obstruction (MVO) in this context has not been analyzed yet. The aim of the present study was to characterize the presence of MVO in the RV in a controlled experimental swine model of reperfused anterior myocardial infarction. MATERIALS AND METHODS: Left anterior descending (LAD) artery-perfused area (thioflavin-S staining after selective infusion in LAD artery), infarct size (lack of triphenyltetrazolium-chloride staining) and MVO (lack of thioflavin-S staining in the core of the infarcted area) in the RV were studied. A quantitative (% of the ventricular volume) and semiquantitative (number of segments involved) analysis was carried out both in the RV and LV in a 90-min left anterior descending balloon occlusion and 3-day reperfusion model in swine (n=15). RESULTS: RV infarction and RV MVO (>1 segment) were detected in 9 (60%) and 6 (40%) cases respectively. Mean LAD-perfused area, infarct size and MVO in the RV were 33.8 ± 13%, 13.53 ± 11.7% and 3.4 ± 4.5%. Haematoxylin and eosin stains and electron microscopy of the RV-MVO areas demonstrated generalized cardiomyocyte necrosis and inflammatory infiltration along with patched hemorrhagic areas. Ex-vivo nuclear magnetic resonance (T2 sequences) microimaging of RV-MVO showed, in comparison with remote non-infarcted territories, marked hypointense zones (corresponding to necrosis, inflammation and hemorrhage) in the core of hyperintense regions (corresponding to edema). CONCLUSIONS: In reperfused anterior myocardial infarction, MVO is frequently present in the RV. It is associated with severe histologic repercussion on the RV wall. Nuclear magnetic resonance appears as a promising technique for the noninvasive detection of this phenomenon. Further studies are warranted to evaluate the pathophysiological and clinical implications.

Head-to-head comparison of 1 week versus 6 months CMR-derived infarct size for prediction of late events after STEMI.

Infarct size (IS) at 1 week after ST-elevation myocardial infarction (MI) diminishes during the first months. The incremental prognostic value of IS regression and of scar size (SS) at 6 months is unknown. We compared cardiovascular magnetic resonance (CMR)-derived IS at 1 week and SS at 6 months after MI for predicting late major adverse cardiac events (MACE). 250 patients underwent CMR at 1 week and 6 months after MI. IS and SS were determined as the extent of transmural late enhancement (in >50 % of wall thickness, ETLE). During 163 weeks, 23 late MACE (cardiac death, MI or readmission for heart failure after the 6 months CMR) occurred. Patients with MACE had a larger IS at 1 week (6 [4-9] vs. 3 [1-5], p < .0001) and a larger SS at 6 months (5 [2-6] vs. 3 [1-5], p = .005) than those without MACE. Late MACE rates in IS >median were higher at 1 week (14 vs. 4 %, p = .007) and in SS >median at 6 months (12 vs. 5 %, p = .053). The C-statistic for predicting late MACE of CMR at 1 week and 6 months was comparable (.720 vs. .746, p = .1). Only ETLE at 1 week (HR 1.31 95 % CI [1.14-1.52], p < .0001, per segment) independently predicted late MACE. CMR-derived SS at 6 months does not offer prognostic value beyond IS at 1 week after MI. The strongest predictor of late MACE is ETLE at 1 week.

Ventricular fibrillation conduction through an isthmus of preserved myocardium between radiofrequency lesions.

BACKGROUND: Selective local acceleration of myocardial activation during ventricular fibrillation (VF) contributes information on the interactions between neighboring zones during the arrhythmia. This study analyzes these interactions, centering the observations on an isthmus of myocardium between two radiofrequency (RF) lesions. METHODS: In nine isolated rabbit hearts, a gap of preserved myocardium was established between two RF lesions in the anterolateral left ventricle (LV) wall. Before, during, and after increasing the spatial heterogeneity of VF by local myocardial stretching, VF epicardial recordings were obtained. RESULTS: Local stretch in the anterior LV wall decreased the excitable window (17 ± 7 ms vs 26 ± 7 ms; P < 0.05) and increased the dominant frequency (DFr; 18.9 ± 5.0 Hz vs 15.2 ± 3.6 Hz; P < 0.05) in this zone, without changes in the non-stretched posterolateral zone (25 ± 4 ms vs 27 ± 6 ms, ns and 14.1 ± 2.7 Hz vs 14.3 ± 3.0 Hz, ns). The DFr ratio at both sides of the gap was inversely correlated to the excitable window ratio (R = -0.57; P = 0.002). Before (31% vs 26%), during (29% vs 22%), and after stretch suppression (35% vs 25%), the wavefronts passing through the gap from the posterolateral to the anterior LV wall were seen to predominate. The number of wavefronts that passed from the anterior to the posterolateral LV wall was related to the excitable window in this zone (R = 0.41; P = 0.03). CONCLUSIONS: The VF acceleration induced in the stretched zone does not increase the flow of wavefronts toward the non-stretched zone in the adjacent gap of preserved myocardium. The absence of significant changes in the electrophysiological parameters of the non-stretched myocardium limits the arrival of wavefronts in this zone.

Metabolomic profile of human myocardial ischemia by nuclear magnetic resonance spectroscopy of peripheral blood serum: a translational study based on transient coronary occlusion models.

OBJECTIVES: The aim of this study was to investigate the metabolomic profile of acute myocardial ischemia (MIS) using nuclear magnetic resonance spectroscopy of peripheral blood serum of swine and patients undergoing angioplasty balloon-induced transient coronary occlusion. BACKGROUND: Biochemical detection of MIS is a major challenge. The validation of novel biosignatures is of utmost importance. METHODS: High-resolution nuclear magnetic resonance spectroscopy was used to profile 32 blood serum metabolites obtained (before and after controlled ischemia) from swine (n = 9) and patients (n = 20) undergoing transitory MIS in the setting of planned coronary angioplasty. Additionally, blood serum of control patients (n = 10) was sequentially profiled. Preliminary clinical validation of the developed metabolomic biosignature was undertaken in patients with spontaneous acute chest pain (n = 30). RESULTS: Striking differences were detected in the blood profiles of swine and patients immediately after MIS. MIS induced early increases (10 min) of circulating glucose, lactate, glutamine, glycine, glycerol, phenylalanine, tyrosine, and phosphoethanolamine; decreases in choline-containing compounds and triacylglycerols; and a change in the pattern of total, esterified, and nonesterified fatty acids. Creatine increased 2 h after ischemia. Using multivariate analyses, a biosignature was developed that accurately detected patients with MIS both in the setting of angioplasty-related MIS (area under the curve 0.94) and in patients with acute chest pain (negative predictive value 95%). CONCLUSIONS: This study reports, to the authors' knowledge, the first metabolic biosignature of acute MIS developed under highly controlled coronary flow restriction. Metabolic profiling of blood plasma appears to be a promising approach for the early detection of MIS in patients.

Modifications in ventricular fibrillation and capture capacity induced by a linear radiofrequency lesion.

INTRODUCTION AND OBJECTIVES: An analysis was made of the effects of a radiofrequency-induced linear lesion during ventricular fibrillation and the capacity to capture myocardium through high-frequency pacing. METHODS: Using multiple epicardial electrodes, ventricular fibrillation was recorded in 22 isolated perfused rabbit hearts, analyzing the activation maps upon applying trains of stimuli at 3 different frequencies close to that of the arrhythmia: a) at baseline; b) after radio-frequency ablation to induce a lesion of the left ventricular free wall (length=10 [1] mm), and c) after lengthening the lesion (length=23 [2] mm). RESULTS: Following lesion induction, the regularity of the recorded signals decreased and significant variations in the direction of the activation fronts were observed. On lengthening the lesion, there was a slight increase in the episodes with at least 3 consecutive captures when pacing at cycles 10% longer than the arrhythmia (baseline: 0.6 [0.7]; initial lesion: 1 [1], no significant differences; lengthened lesion: 3 [2.8]; P<.001), while a decrease was observed in those obtained upon pacing at cycles 10% shorter than the arrhythmia. CONCLUSIONS: The radio-frequency -induced lesion increases the heterogeneity of myocardial activation during ventricular fibrillation and modifies arrival of the activation fronts in the adjacent zones. High-frequency pacing during ventricular fibrillation produces occasional captures during at least 3 consecutive stimuli. The lengthened lesion in turn slightly increases capture capacity when using cycles slightly longer than the arrhythmia.

Antigen carbohydrate 125 and brain natriuretic peptide serial measurements for risk stratification following an episode of acute heart failure.

BACKGROUND: The prognostic utility of combining serial measurements of brain natriuretic peptide (BNP) and antigen carbohydrate 125 (CA125) is largely unknown. The aim of this work is to assess the prognostic utility of serial measurements of BNP, CA125, and their optimal combination for predicting long-term mortality, following a hospitalization for acute heart failure (AHF). METHODS AND RESULTS: We analyzed 293 consecutive patients admitted with AHF where CA125 and BNP were measured at discharge (T1) and at the first ambulatory visit (T2: median 31 days after discharge). Biomarkers were evaluated as snapshot determinations or as serial changes in absolute, relative or categorical changes and related to subsequent mortality with Cox regression analysis. The incremental prognostic value added by each biomarker was evaluated by the integrated discrimination improvement (IDI) index. During a median follow-up of 18 months, 91 deaths (31.1%) were identified. From the different metrics tested, the categorical changes in CA125 (Normalization: decreasing to≤35 U/ml at T2; Decreasing but not normalization: decreasing but T2>35 U/ml; small-increase: increasing but T2≤35 U/ml and; high-increase: increasing and T2>35 U/ml) showed the best discriminative accuracy. For BNP none of the serial changes metrics tested were superior to a single determination at T2 (BNP≥100 pg/ml). Adding these two biomarkers characterization to the clinical model, resulted in a 9.21% (p<0.001) gain in IDI index. CONCLUSIONS: In patients discharged for AHF, CA125 modeled as a pre-post categorical change, and BNP as a single determination at T2, resulted in the best marker combination for predicting all-cause mortality.