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.