RESUMEN
INTRODUCTION: Focal impulses (FI) and rotors are sources associated with the initiation and maintenance of atrial fibrillation (AF). Their ablation results in a lower recurrence rate. The aim of this study was to characterize for the first time the spatial relationship between such sources and atrial low voltage zones (LVZ) representing fibrosis. METHODS: Twenty-five consecutive patients undergoing their first ablation for persistent AF were included. Voltage mapping of both atria was done during AF. Endocardial mapping of FI and rotors (sources) was performed using a basket catheter and displayed using RhythmView(TM) (Topera Inc.) before ablation. Spatial relationship of LVZ and sources was analyzed. RESULTS: LVZs covered 13 ± 12% of right atrial (RA) endocardial surface and 33 ± 25% of left atrial (LA) endocardial surface. The median number of sources was 1 [1-3] in RA and 3 [1-4] in LA. Of LA sources, 18 (30%) were definitely not associated with LVZs or pulmonary vein (PV) antra. Of RA sources, 32 (84%) were remote from LVZ. During ablation of such sources substantial cycle length (CL) prolongation or AF conversion occurred in 11/23 patients (48%). Altogether, 8/11 (73%) of these pertinent sources were located remotely from LVZ and PV antra. CONCLUSIONS: There is a wide discrepancy in distribution of LVZ areas and sites of identified rotors. Site and incidence of FIRM sources appear to be unpredictable with atrial substrate mapping. Further prospective, randomized studies are necessary to elucidate the impact of additional ablation of such sources in patients with persistent or longstanding persistent AF.
Asunto(s)
Potenciales de Acción , Fibrilación Atrial/fisiopatología , Atrios Cardíacos/fisiopatología , Sistema de Conducción Cardíaco/fisiopatología , Anciano , Fibrilación Atrial/diagnóstico , Fibrilación Atrial/cirugía , Ablación por Catéter , Técnicas Electrofisiológicas Cardíacas , Femenino , Fibrosis , Atrios Cardíacos/patología , Atrios Cardíacos/cirugía , Sistema de Conducción Cardíaco/patología , Sistema de Conducción Cardíaco/cirugía , Frecuencia Cardíaca , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Factores de Tiempo , Resultado del TratamientoRESUMEN
BACKGROUND: Cinaciguat (BAY 58-2667) is the first of a new class of soluble guanylate cyclase activators in clinical development for acute decompensated heart failure. We aimed to assess the hemodynamic effects, safety, and tolerability of intravenous cinaciguat in patients with acute decompensated heart failure (pulmonary capillary wedge pressure > or =18 mm Hg). METHODS AND RESULTS: After initial dose finding (part A; n=27), cinaciguat was evaluated in the nonrandomized, uncontrolled proof-of-concept part of the study (part B; n=33) using a starting dose of 100 microg/h, which could be titrated depending on hemodynamic response. Patients were categorized as responders if their pulmonary capillary wedge pressure decreased by > or =4 mm Hg compared with baseline. Final doses of cinaciguat after 6 hours of infusion in part B were 50 microg/h (n=2), 200 microg/h (n=12), and 400 microg/h (n=16). Compared with baseline, a 6-hour infusion of cinaciguat led to significant reductions in pulmonary capillary wedge pressure (-7.9 mm Hg), mean right atrial pressure (-2.9 mm Hg), mean pulmonary artery pressure (-6.5 mm Hg), pulmonary vascular resistance (-43.4 dynes . s . cm(-5)), and systemic vascular resistance (-597 dynes . s . cm(-5)), while increasing heart rate by 4.4 bpm and cardiac output by 1.68 L/min. The responder rate was 53% after 2 hours, 83% after 4 hours, and 90% after 6 hours. Cinaciguat was well tolerated, with 13 of 60 patients reporting 14 drug-related treatment-emergent adverse events of mild to moderate intensity, most commonly hypotension. CONCLUSIONS: Cinaciguat has potent preload- and afterload-reducing effects, increasing cardiac output. Further investigation of cinaciguat for acute decompensated heart failure is warranted.
Asunto(s)
Benzoatos/uso terapéutico , Guanilato Ciclasa/efectos de los fármacos , Insuficiencia Cardíaca/tratamiento farmacológico , Hemodinámica/efectos de los fármacos , Receptores Citoplasmáticos y Nucleares/efectos de los fármacos , Vasodilatadores/uso terapéutico , Enfermedad Aguda , Adulto , Anciano , Anciano de 80 o más Años , Benzoatos/administración & dosificación , Benzoatos/efectos adversos , Benzoatos/farmacología , Presión Sanguínea/efectos de los fármacos , Gasto Cardíaco/efectos de los fármacos , Activación Enzimática/efectos de los fármacos , Femenino , Insuficiencia Cardíaca/fisiopatología , Frecuencia Cardíaca/efectos de los fármacos , Humanos , Hipotensión/inducido químicamente , Infusiones Intravenosas , Masculino , Persona de Mediana Edad , Presión Esfenoidal Pulmonar/efectos de los fármacos , Guanilil Ciclasa Soluble , Resistencia Vascular/efectos de los fármacos , Vasodilatadores/administración & dosificación , Vasodilatadores/efectos adversos , Vasodilatadores/farmacologíaRESUMEN
BACKGROUND: BAY 41-2272 is a recently introduced novel orally available agent that directly stimulates soluble guanylate cyclase (sGC) and sensitizes it to its physiological stimulator, nitric oxide. To date, its therapeutic actions in congestive heart failure (CHF) remain undefined. We characterized the cardiorenal actions of intravenous BAY 41-2272 in a canine model of CHF and compared it to nitroglycerin (NTG). METHODS AND RESULTS: CHF was induced by rapid ventricular pacing for 10 days. Cardiorenal and humoral function were assessed at baseline and with administration of 2 doses of BAY 41-2272 (2 and 10 micro g x kg(-1) x min(-1); n=8) or NTG (1 and 5 micro g x kg(-1) x min(-1); n=6). Administration of 10 micro g x kg(-1) x min(-1) BAY 41-2272 reduced mean arterial pressure (113+/-8 to 94+/-6 mm Hg; P<0.05), pulmonary artery pressure (29+/-2 to 25+/-2 mm Hg; P<0.05), and pulmonary capillary wedge pressure (25+/-2 to 20+/-2 mm Hg; P<0.05). Cardiac output (2.1+/-0.2 to 2.3+/-0.2 L/min; P<0.05) and renal blood flow (131+/-17 to 162+/-18 mL/min; P<0.05) increased. Glomerular filtration rate was maintained. There were no changes in plasma renin activity, angiotensin II, or aldosterone. NTG mediated similar hemodynamic changes and additionally decreased right atrial pressure and pulmonary vascular resistance. CONCLUSION: The new sGC stimulator BAY 41-2272 potently unloaded the heart, increased cardiac output, and preserved glomerular filtration rate without activation of the renin-angiotensin-aldosterone system in experimental CHF. These beneficial properties make direct sGC stimulation with BAY 41-2272 a promising new strategy for the treatment of cardiovascular diseases such as CHF.