RESUMEN
INTRODUCTION: Radiofrequency (RF) and cryoablation are routinely used to treat arrhythmias, but the extent and time course of edema associated with the two different modalities is unknown. Our goal was to follow the lesion maturation and edema formation after RF and cryoablation using serial magnetic resonance imaging (MRI). METHODS AND RESULTS: Ventricular ablation was performed in a canine model (n = 11) using a cryo or an irrigated RF catheter. T2-weighted (T2w) edema imaging and late gadolinium enhancement (LGE)-MRI were done immediately (0 day: acute), 1 to 2 weeks (subacute), and 8 to 12 weeks (chronic) after ablation. After the final MRI, excised hearts underwent pathological evaluation. As a result, 45 ventricular lesions (cryo group: 20; RF group: 25) were evaluated. Acute LGE volume was not significantly different but acute edema volume in cryo group was significantly smaller (1225.0 ± 263.5 vs 1855.2 ± 520.5 mm3 ; P = 0.01). One week after ablation, edema still existed in both group but was similar in size. Two weeks after ablation there was no edema in either of the groups. In the chronic phase, the lesion volume for cryo and RF in LGE-MRI (296.7 ± 156.4 vs 281.6 ± 140.8 mm3 ; P = 0.73); and pathology (243.3 ± 125.9 vs 214.5 ± 148.6 mm3 ; P = 0.49), as well as depth, was comparable. CONCLUSIONS: When comparing cryo and RF lesions of similar chronic size, acute edema is larger for RF lesions. Edema resolves in both cryo and RF lesions in 1 to 2 weeks.
Asunto(s)
Criocirugía/efectos adversos , Edema Cardíaco/diagnóstico por imagen , Ventrículos Cardíacos/diagnóstico por imagen , Ventrículos Cardíacos/cirugía , Imagen por Resonancia Magnética , Miocardio/patología , Ablación por Radiofrecuencia/efectos adversos , Animales , Medios de Contraste/administración & dosificación , Perros , Edema Cardíaco/etiología , Edema Cardíaco/patología , Ventrículos Cardíacos/patología , Meglumina/administración & dosificación , Meglumina/análogos & derivados , Compuestos Organometálicos/administración & dosificación , Valor Predictivo de las Pruebas , Factores de TiempoRESUMEN
AIMS: The goals of this study were to develop a method that combines cryoablation with real-time magnetic resonance imaging (MRI) guidance for pulmonary vein isolation (PVI) and to further quantify the lesion formation by imaging both acute and chronic cryolesions. METHODS AND RESULTS: Investigational MRI-compatible cryoablation devices were created by modifying cryoballoons and cryocatheters. These devices were used in canines (n = 8) and a complete series of lesions (PVI: n = 5, superior vena cava: n = 4, focal: n = 13) were made under real-time MRI guidance. Late gadolinium enhancement (LGE) magnetic resonance imaging was acquired at acute and chronic time points. Late gadolinium enhancement magnetic resonance imagings show a significant amount of acute tissue injury immediately following cryoablation which subsides over time. In the pulmonary veins, scar covered 100% of the perimeter of the ostium of the veins acutely, which subsided to 95.6 ± 4.3% after 3 months. Focal point lesions showed significantly larger acute enhancement volumes compared to the volumes estimated from gross pathology measurements (0.4392 ± 0.28 cm3 vs. 0.1657 ± 0.08 cm3, P = 0.0043). Additionally, our results with focal point ablations indicate that freeze-zone formation reached a maximum area after 120 s. CONCLUSION: This study reports on the development of an MRI-based cryoablation system and shows that with acute cryolesions there is a large area of reversible injury. Real-time MRI provides the ability to visualize the freeze-zone formation during the freeze cycle and for focal lesions reaches a maximum after 120 s suggesting that for maximizing lesion size 120 s might be the lower limit for dosing duration.
Asunto(s)
Criocirugía , Imagen por Resonancia Magnética Intervencional , Venas Pulmonares/cirugía , Vena Cava Superior/cirugía , Animales , Criocirugía/efectos adversos , Perros , Imagen por Resonancia Magnética Intervencional/efectos adversos , Venas Pulmonares/diagnóstico por imagen , Venas Pulmonares/patología , Factores de Riesgo , Factores de Tiempo , Vena Cava Superior/diagnóstico por imagen , Vena Cava Superior/patologíaRESUMEN
BACKGROUND: Cardiac resynchronization therapy (CRT) is a major advance for treatment of patients with dyssynchronous heart failure (DHF). However, our understanding of DHF-associated remodeling of subcellular structure and function and their restoration after CRT remains incomplete. METHODS AND RESULTS: We investigated subcellular heterogeneity of remodeling of structures and proteins associated with excitation-contraction coupling in cardiomyocytes in DHF and after CRT. Three-dimensional confocal microscopy revealed subcellular heterogeneity of ryanodine receptor (RyR) density and the transverse tubular system (t-system) in a canine model of DHF. RyR density at the ends of lateral left ventricular cardiomyocytes was higher than that in cell centers, whereas the t-system was depleted at cell ends. In anterior left ventricular cardiomyocytes, however, we found a similar degree of heterogeneous RyR remodeling, despite preserved t-system. Synchronous heart failure was associated with marginal heterogeneity of RyR density. We used rapid scanning confocal microscopy to investigate effects of heterogeneous structural remodeling on calcium signaling. In DHF, diastolic Ca(2+) spark density was smaller at cell ends versus centers. After CRT, subcellular heterogeneity of structures and function was reduced. CONCLUSIONS: RyR density exhibits remarkable subcellular heterogeneity in DHF. RyR remodeling occurred in lateral and anterior cardiomyocytes, but remodeling of t-system was confined to lateral myocytes. These findings indicate that different mechanisms underlie remodeling of RyRs and t-system. Furthermore, we suggest that ventricular dyssynchrony exacerbates subcellular remodeling in heart failure. CRT efficiently reduced subcellular heterogeneity. These results will help to explain remodeling of excitation-contraction coupling in disease and restoration after CRT.
Asunto(s)
Terapia de Resincronización Cardíaca , Insuficiencia Cardíaca/patología , Insuficiencia Cardíaca/terapia , Animales , Modelos Animales de Enfermedad , Perros , Acoplamiento Excitación-Contracción , Insuficiencia Cardíaca/etiología , Microscopía Confocal , Miocitos Cardíacos/patología , Canal Liberador de Calcio Receptor de Rianodina , Remodelación VentricularRESUMEN
Heart failure (HF) is accompanied by complex alterations in myocardial energy metabolism. Up to 40% of HF patients have dyssynchronous ventricular contraction, which is an independent indicator of mortality. We hypothesized that electromechanical dyssynchrony significantly affects metabolic remodeling in the course of HF. We used a canine model of tachypacing-induced HF. Animals were paced at 200 bpm for 6 weeks either in the right atrium (synchronous HF, SHF) or in the right ventricle (dyssynchronous HF, DHF). We collected biopsies from left ventricular apex and performed comprehensive metabolic pathway analysis using multi-platform metabolomics (GC/MS; MS/MS; HPLC) and LC-MS/MS label-free proteomics. We found important differences in metabolic remodeling between SHF and DHF. As compared to Control, ATP, phosphocreatine (PCr), creatine, and PCr/ATP (prognostic indicator of mortality in HF patients) were all significantly reduced in DHF, but not SHF. In addition, the myocardial levels of carnitine (mitochondrial fatty acid carrier) and fatty acids (12:0, 14:0) were significantly reduced in DHF, but not SHF. Carnitine parmitoyltransferase I, a key regulatory enzyme of fatty acid ß-oxidation, was significantly upregulated in SHF but was not different in DHF, as compared to Control. Both SHF and DHF exhibited a reduction, but to a different degree, in creatine and the intermediates of glycolysis and the TCA cycle. In contrast to this, the enzymes of creatine kinase shuttle were upregulated, and the enzymes of glycolysis and the TCA cycle were predominantly upregulated or unchanged in both SHF and DHF. These data suggest a systemic mismatch between substrate supply and demand in pacing-induced HF. The energy deficit observed in DHF, but not in SHF, may be associated with a critical decrease in fatty acid delivery to the ß-oxidation pipeline, primarily due to a reduction in myocardial carnitine content.
Asunto(s)
Metabolismo Energético/fisiología , Insuficiencia Cardíaca/metabolismo , Redes y Vías Metabólicas/fisiología , Metabolómica/métodos , Miocardio/metabolismo , Disfunción Ventricular/metabolismo , Animales , Cromatografía Líquida de Alta Presión , Ciclo del Ácido Cítrico/fisiología , Creatina/metabolismo , Creatina Quinasa/metabolismo , Perros , Cromatografía de Gases y Espectrometría de Masas , Glucólisis , Proteómica/métodos , Espectrometría de Masas en Tándem , Factores de Tiempo , Disfunción Ventricular/fisiopatologíaRESUMEN
Sarcomeres are the basic contractile units of cardiac myocytes. Recent studies demonstrated remodeling of sarcomeric proteins in several diseases, including genetic defects and heart failure. Here we investigated remodeling of sarcomeric α-actinin in two models of heart failure, synchronous (SHF) and dyssynchronous heart failure (DHF), as well as a model of cardiac resynchronization therapy (CRT). We applied three-dimensional confocal microscopy and quantitative methods of image analysis to study isolated cells from our animal models. 3D Fourier analysis revealed a decrease of the spatial regularity of the α-actinin distribution in both SHF and DHF versus control cells. The spatial regularity of α-actinin in DHF cells was reduced when compared with SHF cells. The spatial regularity of α-actinin was partially restored after CRT. We found longitudinal depositions of α-actinin in SHF, DHF and CRT cells. These depositions spanned adjacent Z-disks and exhibited a lower density of α-actinin than in the Z-disk. Differences in the occurrence of depositions between the SHF, CRT and DHF models versus control were significant. Also, CRT cells exhibited a higher occurrence of depositions versus SHF, but not DHF cells. Other sarcomeric proteins did not accumulate in the depositions to the same extent as α-actinin. We did not find differences in the expression of α-actinin protein and its encoding gene in our animal models. In summary, our studies indicate that HF is associated with two different types of remodeling of α-actinin and only one of those was reversed after CRT. We suggest that these results can guide us to an understanding of remodeling of structures and function associated with sarcomeres.