Gut Microbiota and Derived Short-Chain Fatty Acids Are Linked to Evolution of Heart Failure Patients.

There is a lack of direct evidence regarding gut microbiota dysbiosis and changes in short-chain fatty acids (SCFAs) in heart failure (HF) patients. We sought to assess any association between gut microbiota composition, SCFA production, clinical parameters, and the inflammatory profile in a cohort of newly diagnosed HF patients. In this longitudinal prospective study, we enrolled eighteen newly diagnosed HF patients. At admission and after 12 months, blood samples were collected for the assessment of proinflammatory cytokines, monocyte populations, and endothelial dysfunction, and stool samples were collected for analysis of gut microbiota composition and quantification of SCFAs. Twelve months after the initial HF episode, patients demonstrated improved clinical parameters and reduced inflammatory state and endothelial dysfunction. This favorable evolution was associated with a reversal of microbiota dysbiosis, consisting of the increment of health-related bacteria, such as genus Bifidobacterium, and levels of SCFAs, mainly butyrate. Furthermore, there was a decrease in the abundance of pathogenic bacteria. In vitro, fecal samples collected after 12 months of follow-up exhibited lower inflammation than samples collected at admission. In conclusion, the favorable progression of HF patients after the initial episode was linked to the reversal of gut microbiota dysbiosis and increased SCFA production, particularly butyrate. Whether restoring butyrate levels or promoting the growth of butyrate-producing bacteria could serve as a complementary treatment for these patients deserves further studies.

In vivo ratiometric optical mapping enables high-resolution cardiac electrophysiology in pig models.

AIMS: Cardiac optical mapping is the gold standard for measuring complex electrophysiology in ex vivo heart preparations. However, new methods for optical mapping in vivo have been elusive. We aimed at developing and validating an experimental method for performing in vivo cardiac optical mapping in pig models. METHODS AND RESULTS: First, we characterized ex vivo the excitation-ratiometric properties during pacing and ventricular fibrillation (VF) of two near-infrared voltage-sensitive dyes (di-4-ANBDQBS/di-4-ANEQ(F)PTEA) optimized for imaging blood-perfused tissue (n = 7). Then, optical-fibre recordings in Langendorff-perfused hearts demonstrated that ratiometry permits the recording of optical action potentials (APs) with minimal motion artefacts during contraction (n = 7). Ratiometric optical mapping ex vivo also showed that optical AP duration (APD) and conduction velocity (CV) measurements can be accurately obtained to test drug effects. Secondly, we developed a percutaneous dye-loading protocol in vivo to perform high-resolution ratiometric optical mapping of VF dynamics (motion minimal) using a high-speed camera system positioned above the epicardial surface of the exposed heart (n = 11). During pacing (motion substantial) we recorded ratiometric optical signals and activation via a 2D fibre array in contact with the epicardial surface (n = 7). Optical APs in vivo under general anaesthesia showed significantly faster CV [120 (63-138) cm/s vs. 51 (41-64) cm/s; P = 0.032] and a statistical trend to longer APD90 [242 (217-254) ms vs. 192 (182-233) ms; P = 0.095] compared with ex vivo measurements in the contracting heart. The average rate of signal-to-noise ratio (SNR) decay of di-4-ANEQ(F)PTEA in vivo was 0.0671 ± 0.0090 min-1. However, reloading with di-4-ANEQ(F)PTEA fully recovered the initial SNR. Finally, toxicity studies (n = 12) showed that coronary dye injection did not generate systemic nor cardiac damage, although di-4-ANBDQBS injection induced transient hypotension, which was not observed with di-4-ANEQ(F)PTEA. CONCLUSIONS: In vivo optical mapping using voltage ratiometry of near-infrared dyes enables high-resolution cardiac electrophysiology in translational pig models.

Implications of bipolar voltage mapping and magnetic resonance imaging resolution in biventricular scar characterization after myocardial infarction.

AIMS: We aimed to study the differences in biventricular scar characterization using bipolar voltage mapping compared with state-of-the-art in vivo delayed gadolinium-enhanced cardiac magnetic resonance (LGE-CMR) imaging and ex vivo T1 mapping. METHODS AND RESULTS: Ten pigs with established myocardial infarction (MI) underwent in vivo scar characterization using LGE-CMR imaging and high-density voltage mapping of both ventricles using a 3.5-mm tip catheter. Ex vivo post-contrast T1 mapping provided a high-resolution reference. Voltage maps were registered onto the left and right ventricular (LV and RV) endocardium, and epicardium of CMR-based geometries to compare voltage-derived scars with surface-projected 3D scars. Voltage-derived scar tissue of the LV endocardium and the epicardium resembled surface projections of 3D in vivo and ex vivo CMR-derived scars using 1-mm of surface projection distance. The thinner wall of the RV was especially sensitive to lower resolution in vivo LGE-CMR images, in which differences between normalized low bipolar voltage areas and CMR-derived scar areas did not decrease below a median of 8.84% [interquartile range (IQR) (3.58, 12.70%)]. Overall, voltage-derived scars and surface scar projections from in vivo LGE-CMR sequences showed larger normalized scar areas than high-resolution ex vivo images [12.87% (4.59, 27.15%), 18.51% (11.25, 24.61%), and 9.30% (3.84, 19.59%), respectively], despite having used optimized surface projection distances. Importantly, 43.02% (36.54, 48.72%) of voltage-derived scar areas from the LV endocardium were classified as non-enhanced healthy myocardium using ex vivo CMR imaging. CONCLUSION: In vivo LGE-CMR sequences and high-density voltage mapping using a conventional linear catheter fail to provide accurate characterization of post-MI scar, limiting the specificity of voltage-based strategies and imaging-guided procedures.

The COR trial: a randomized study with continuous rhythm monitoring to compare the efficacy of cryoenergy and radiofrequency for pulmonary vein isolation.

BACKGROUND: Results from randomized trials designed to compare cryoenergy with radiofrequency for pulmonary vein (PV) isolation are lacking. OBJECTIVE: To compare the efficacy of a simplified strategy for PV cryoablation (group C) vs PV isolation with open-irrigated radiofrequency catheters (group R). METHODS: Fifty patients with paroxysmal atrial fibrillation (AF) and 4 independent PVs received a Reveal XT implantable cardiac monitor and were randomized to group C or group R. In group C, PV ablation was done with a single Arctic Front balloon (23 or 28 mm) per patient and two 300-second applications per PV. No further applications were delivered to close residual conduction gaps. In group R, bidirectional PV conduction block was pursued with Lasso and Navistar ThermoCool catheters and the CARTO system. The primary end point was the proportion of patients remaining free from AF recurrences ≥2 minutes without taking antiarrhythmic drugs 12 months after ablation. RESULTS: The primary end point was met by 12 (48%) patients in group C and 25 (68%) patients in group R (odds ratio 0.43; P = .05). This difference disappeared after adjustment for acute procedural outcome. In patients for whom all 4 PVs were blocked at the end of the procedure, there was no difference between group C and group R in the primary end point (67% vs 68%; P = .94). CONCLUSIONS: The efficacy of the simplified strategy for PV cryoablation tested in this study is inferior to PV isolation using open-irrigated radiofrequency catheters with electrophysiological and electroanatomical guidance. Complete PV conduction block is critical to the success of AF ablation.

Early recurrence is a predictor of late failure in surgical ablation of atrial fibrillation.

We sought to determine if early recurrence of atrial fibrillation (AF) after surgical ablation is a risk factor of late failure. Between February 2004 to May 2009, 106 patients underwent surgical ablation of concomitant permanent AF with radiofrequency. Operations primarily consisted of valve surgery in 85% of patients. Hospital mortality was 2.8% (n = 3). The median follow-up was 37 months (interquartile rank 12-77), and was complete in 99% of patients. Freedom from AF was 82%, 76% and 68% at one, two and three years, respectively. Patients with early recurrence of AF had less prevalence of sinus rhythm in late follow-up (P < 0.001). Multivariate Cox regression analysis showed that AF duration [hazard ratio (HR) 1.014, 95% CI 1.009-1.020, P < 0.001] and early recurrence of AF (HR 3.45, 95% CI 1.50-7.95, P = 0.004) were independent risk factors for failure. In conclusion, in our series, early recurrence of AF after surgical ablation is a strong predictor of late failure.

[Clinical and Preclinical Heart Failure Research Network (REDINSCOR). Instituto de Salud Carlos III Cooperative Special Topic Research Networks]. / Red de investigación clínica y básica en insuficiencia cardiaca (REDINSCOR). Redes temáticas de investigación cooperativa del Instituto de Salud Carlos III.

Heart failure is a prevalent condition that is associated with high morbidity and mortality and that places a substantial demand on healthcare resources. As the condition often affects older individuals with comorbidities, its treatment requires the implementation of an integrated model of care that can be applied in primary care, in hospitals, and in the patient's home. The use of heart failure units has improved quality of life in these patients and has reduced hospital admissions. However, in Spain integrated care has not yet been widely implemented. Clinical and preclinical research on heart failure is complex and, consequently, it is essential for investigators to work together in research networks. As a result, 16 Spanish centers have organized themselves into a heart failure research network (REDINSCOR). This network is considering the establishment of a national heart failure registry and is involved in seven research projects, whose subjects range from molecular biology and cell physiology to diagnosis, treatment, and the development of integrated healthcare models.

Pathological effects of pulmonary vein beta-radiation in a swine model.

INTRODUCTION: Atrial fibrillation (AF) may be triggered by ectopic beats originating in sleeves of atrial myocardium entering the pulmonary veins (PVs). PV isolation by means of circumferential ostial or atrial radiofrequency ablation is an effective but also a difficult and long procedure, requiring extensive applications that can have serious potential complications. Our objective was to examine pathological effects of PV beta-radiation, particularly the ability to destroy PV myocardial sleeves without inducing PV stenosis and other unwanted effects, in order to establish its potential feasibility for the treatment of AF. METHODS AND RESULTS: Ten minipigs were studied. A phosphorus-32 source wire centered within a 2.5-mm diameter balloon catheter (Galileo III Intravascular Radiotherapy System, Guidant, Santa Clara, CA, USA) was used to deliver beta-radiation to the superior wall of the right PV trunk. Pathological analysis was performed either immediately after ablation (2 pigs) or 81 +/- 27 days later (8 pigs). Acute effects of PV beta-radiation consisted of endothelial denudation covered by white thrombus, elastic lamina disruption, and PV sleeve necrosis. Late effects consisted of mild focal neointimal hyperplasia that reduced the PV luminal area by only 1.3 +/- 1.8%, elastic lamina thickening, and PV sleeve fibrosis. Four of these 8 PVs were completely re-endothelized. Lesions were transmural in 6 of 10 radiated PVs and segmental, involving 28 +/- 7% of the right PV perimeter. CONCLUSION: Intravascular beta-radiation can induce transmural necrosis and fibrosis of PV myocardial sleeves without PV stenosis and other unwanted effects, which supports a potential usefulness of this energy source in the treatment of AF.

Supresión de arritmias supraventriculares y ventriculares. ¿Qué papel pueden desempeñar los ácidos grasos omega-3? / Suppression of supraventricular and ventricular arrhythmias. What is the role of omega-3 fatty acids?

Los ácidos grasos poliinsaturados n-3 u omega-3 son una prometedora terapia dietética preventiva para la enfermedad cardiovascular, y constituyen un método seguro y efectivo para la prevención de la muerte súbita. El pescado graso es la fuente dietética principal de ácidos grasos poliinsaturados n-3. En los últimos años, las propiedades antiarrítmicas de estos ácidos grasos han sido extensamente investigadas. Se han propuesto y estudiado varios mecanismos para explicar este efecto antiarrítmico, pero hasta el momento ninguno de ellos ha sido validado de forma definitiva. En esta revisión se resumen los conocimientos epidemiológicos que sostienen el uso de los ácidos grasos n-3 con esta indicación, la evidencia básica y clínica alcanzada en estudios experimentales en animales y humanos, así como las teorías actuales sobre el mecanismo antiarrítmico de esta clase de ácidos grasos poliinsaturados (AU)

Dietary n-3 or omega-3 polyunsaturated fatty acids show promise as preventive therapy for cardiovascular disease, offering a safe and effective means of reducing sudden death. Oily fish is the main dietary source of omega-3 polyunsaturated fatty acid. In recent years, the anti-arrhythmic effects of polyunsaturated fatty acids have been extensively investigated. Several mechanisms that could explain these antiarrhythmic effects have been proposed and have been investigated. However, to date, no definitive mechanism has been identified. This review summarizes the epidemiological data supporting the use of omega-3 fatty acids in this context, the preclinical and clinical evidence revealed by animal and human studies, and current hypotheses about the antiarrhythmic mechanism of this class of polyunsaturated fatty acid (AU)

Ablation of electrograms with an isolated, delayed component as treatment of unmappable monomorphic ventricular tachycardias in patients with structural heart disease.

OBJECTIVES: We sought to evaluate the feasibility of identifying and ablating the substrate of unmappable ventricular tachycardia (VT). BACKGROUND: Noninducible and nonstable VT cannot be ablated by the conventional approach. METHODS: We studied 24 patients with documented monomorphic VT. Twenty-one patients had ischemic cardiomyopathy, two had nonischemic cardiomyopathy, and one had tetralogy of Fallot. Twelve patients had an implantable cardioverter-defibrillator. Conventional activation mapping was not possible in 18 patients: at least 1 of the clinical VTs or the clinical VT was not inducible in 12 patients, and VT was not tolerated in 6 patients. This group had experienced between 1 and 106 VT episodes in the month before the ablation procedure. Endocardial electroanatomic activation maps (Carto System) during sinus rhythm (SR) and right ventricular apex (RVA) pacing were obtained to define areas for which an electrogram displayed isolated, delayed components (E-IDC). These electrograms were characterized by double or multiple components separated by >/=50 ms. RESULTS: One area of E-IDC was recorded in 20 patients, and 2 or more were recorded in 4 patients. In 23 patients, these areas were detected during RVA pacing; in only 14 during SR. An E-IDC area related to the clinical VT was identified in each patient. Ablation guided by E-IDC suppressed all but one clinical VT whose inducibility suppression was tested. During a follow-up period of 9 +/- 4 months, three patients had recurrences of the ablated VT and two of a different VT. CONCLUSIONS: Electrograms with IDCs related to clinical VT can be identified in the majority of patients during RVA pacing. Radiofrequency ablation of E-IDC seems effective in controlling unmappable VT.

Usefulness of paced activation sequence mapping in catheter ablation of accessory pathways.

INTRODUCTION: Radiofrequency (RF) ablation of accessory pathways (APs) is often a time-consuming procedure, mainly because conventional criteria have modest accuracy. Thus, additional mapping criteria are desirable. Our hypothesis was that comparison of paced atrial activation sequences with that obtained during orthodromic AV reentrant tachycardia might be useful for locating the atrial insertion of single APs. METHODS AND RESULTS: The study included 15 patients with a single AP referred for ablation. Analysis of the atrial activation sequence was simplified by measuring the activation time (AT) that elapsed between two atrial reference points placed next to the AV annulus on either side of the area containing the AP. Ablation was guided by conventional criteria. Before each RF delivery, a short pacing train was delivered from the ablation catheter and, after verification of atrial capture, the AT was compared with the AT obtained during orthodromic tachycardia. Fifty sites of RF delivery were appropriate for analysis. The multivariate model with the highest predictive power included a deviation of AT between pacing and tachycardia < or = 5 msec (P < 0.001), a local AV ratio > or = 1 (P = 0.04), and stability of the local electrogram (P = 0.05). The combination of all these criteria predicted a successful application with high sensitivity, specificity, and positive predictive value (92%, 86%, and 71% respectively). To validate the method prospectively, 10 additional consecutive patients underwent an AP ablation procedure guided by these criteria. CONCLUSION: This technique seems to be highly accurate in selecting the atrial site for RF ablation of single APs.