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BACKGROUND: Ischemic heart disease (IHD) has been linked to an increased risk of atrial fibrillation (AF). However, data are sparse regarding the role of IHD in AF recurrence after catheter ablation. OBJECTIVE: We sought to investigate whether preexisting or new-onset IHD is associated with a greater risk of AF recurrence after ablation. METHODS: With use of Danish nationwide registries, all patients undergoing first-time AF ablation in Denmark from 2010 to 2020 were identified. The primary outcome was AF recurrence defined by AF-related hospital admission or antiarrhythmic drug use within 1 year after ablation excluding a 3-month blanking period. IHD was defined as an International Classification of Diseases, Tenth Revision diagnosis of IHD or prior coronary revascularization. RESULTS: Of 12,162 patients undergoing first-time ablation for AF (mean age, 62 years; 30% female), 20% had preexisting IHD. Preexisting IHD was associated with an increased risk of AF recurrence in univariable log-binomial logistic regression (relative risk, 1.09; 95% CI, 1.04-1.14; P < .001). However, after multivariable adjustment including procedural year, preexisting IHD was no longer associated with an increased risk of AF recurrence (relative risk, 1.02; 95% CI, 0.97-1.06; P = .42). In a nested case-control study of those without preexisting IHD before ablation (n = 9778), newly diagnosed IHD after ablation was associated with an increased risk of AF recurrence in multivariable analysis (hazard ratio, 3.03; 95% CI, 1.84-4.99; P < .001). CONCLUSION: The presence of IHD does not appear to reduce the effectiveness of AF ablation procedures. However, the emergence of IHD after AF ablation may serve as a trigger for AF that is insufficiently suppressed by prior ablation.
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BACKGROUND: Currently there is no reliable medical treatment for aortic regurgitation (AR). METHODS: Thirty-nine Sprague-Dawley rats underwent creation of AR or sham operation. Treated rats were assigned to early or late institution of sildenafil therapy (100 mg/kg/day) for a total of 10 weeks. Treatment-effects were measured by serial echocardiography, invasive hemodynamic measurements, and tissue analysis. RESULTS: Rats assigned to early treatment developed less remodeling than untreated rats. Thus, left ventricular (LV) dilation was blunted by sildenafil with end-systolic diameter being significantly smaller (6.6 ± 0.4 vs. 7.7 ± 0.4 mm, respectively, p < 0.05). Also, LV wall thickness was significantly decreased in treated rats compared to controls (2.23 ± 0.08 vs. 2.16 ± 0.05 mm, p < 0.01). Fractional shortening was improved by treatment (p < 0.05). Myocardial fibrosis was borderline decreased by treatment (p = 0.09). Akt was increased in treated compared to controls (p < 0.05). CONCLUSION: Sildenafil slightly inhibits LV remodeling and improves fractional shortening in rats with AR when treatment is initiated early.
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BACKGROUND: Beta-blockade is contraindicated in severe aortic regurgitation (AR) due to the fear of prolonging diastole and thus aggravate regurgitation. However, this has never been scientifically proven and positive effects of targeting the sympathetic system in AR has been demonstrated in several studies. METHOD: Thirty-nine Sprague-Dawley rats with AR were randomized to ten weeks of medical treatment with carvedilol or no treatment. Treatment was initiated either early or late after AR induction. The effect of carvedilol was assessed by serial echocardiography and invasive hemodynamic measurements. RESULTS: AR resulted in eccentric hypertrophy and left ventricular (LV) dysfunction. LV remodeling and function as measured by echocardiography was unaffected by treatment. LV dimensions were similar between treated and untreated groups and measures of LV performance (including strain and strain rate) were also unaltered. This result was confirmed by invasive measurements showing maximal and minimal pressure-time development, LV volumes, and LV pressures, to be unaltered by treatment. On the contrary, despite relative bradycardia carvedilol did not reflect any negative impact on the heart. CONCLUSION: Carvedilol did not improve left ventricular remodeling or function in rats with surgically induced AR. Despite relative bradycardia, we did not find carvedilol to negatively impact the heart, either when treatment was initiated early or late in the course of disease.
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The development of left ventricular hypertrophy and dysfunction in aortic regurgitation (AR) has only been sparsely studied experimentally. In a new model of chronic AR in rats, we examined activation of molecular pathways involved in myocardial hypertrophy. Chronic AR was produced by damaging one or two valve cusps, resulting in eccentric remodeling and left ventricular dysfunction, with no increase in overall fibrosis. Western blotting showed increased activation of Akt and p38 at 12 weeks and of c-Jun amino-terminal kinase at 2 weeks, decreased activation of extracellular regulated kinase 5 at both 2 and 12 weeks, while activation of calcium/calmodulin-dependent protein kinase II and extracellular regulated kinase 1/2 was unchanged. Expression of calcineurin and ANF was also unchanged. Eccentric hypertrophy and early cardiac dysfunction in experimental AR are associated with a pattern of activation of intracellular pathways different from that seen with pathological hypertrophy in pressure overload, and more similar to that associated with benign physiological hypertrophy.
Asunto(s)
Insuficiencia de la Válvula Aórtica/complicaciones , Hipertrofia Ventricular Izquierda/etiología , Miocardio/metabolismo , Transducción de Señal , Disfunción Ventricular Izquierda/etiología , Animales , Insuficiencia de la Válvula Aórtica/diagnóstico por imagen , Insuficiencia de la Válvula Aórtica/metabolismo , Insuficiencia de la Válvula Aórtica/fisiopatología , Factor Natriurético Atrial/metabolismo , Calcineurina/metabolismo , Proteína Quinasa Tipo 2 Dependiente de Calcio Calmodulina/metabolismo , Enfermedad Crónica , Modelos Animales de Enfermedad , Ecocardiografía Doppler en Color , Quinasas MAP Reguladas por Señal Extracelular/metabolismo , Hipertrofia Ventricular Izquierda/diagnóstico por imagen , Hipertrofia Ventricular Izquierda/metabolismo , Hipertrofia Ventricular Izquierda/fisiopatología , Proteínas Quinasas JNK Activadas por Mitógenos/metabolismo , Masculino , Miocardio/patología , Fosforilación , Proteínas Proto-Oncogénicas c-akt/metabolismo , Ratas , Ratas Sprague-Dawley , Factores de Tiempo , Disfunción Ventricular Izquierda/diagnóstico por imagen , Disfunción Ventricular Izquierda/metabolismo , Disfunción Ventricular Izquierda/fisiopatología , Función Ventricular Izquierda , Proteínas Quinasas p38 Activadas por Mitógenos/metabolismoRESUMEN
OBJECTIVES: Invasive measurements of intracardiac hemodynamics in animal models have allowed important advances in the understanding of cardiac disease. Currently they are performed either through a carotid arteriotomy or via a thoracotomy and apical insertion. Both of these techniques have disadvantages and are not conducive to repeated measurements. Therefore, the purpose of this study was to develop a new technique for measuring intracardiac hemodynamics. METHODS: In 13 male rats, hemodynamic measurements were performed using a new echocardiographically guided percutaneous apical technique. An intravenous catheter was percutaneously inserted into the left ventricle (LV) in the direction of the LV long axis. Through this catheter, a micromanometer-tipped pressure catheter was inserted, and invasive hemodynamic traces were recorded. After LV recordings, the pressure catheter was advanced into the aorta where pressures were obtained. In 11 rats, measurements were repeated after 1 week (n = 2), 2 weeks (n = 4), 3 weeks (n = 4), or 4 weeks (n = 1). In 3 rats, invasive measurements were performed using a carotid arteriotomy before the percutaneous technique. RESULTS: Among the 13 rats subjected to the procedure, the survival rate was 85%. Of the 11 rats that had the procedure repeated, 3 died (27%). The mean differences ± SD when comparing the two techniques were 10 ± 4 mm Hg for the LV end-systolic pressure and 1 ± 1 mm Hg for the LV end-diastolic pressure. The mean procedure times were 21 ± 3 and 6 ± 1 minutes for the carotid and percutaneous techniques, respectively. CONCLUSIONS: We have successfully developed a percutaneous technique for insertion of LV microtip catheters in rats.