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1.
Clin Res Cardiol ; 2024 Feb 15.
Artículo en Inglés | MEDLINE | ID: mdl-38358420

RESUMEN

INTRODUCTION: Cryoballoon (CB) ablation has become a popular method for pulmonary vein isolation (PVI) in atrial fibrillation (AF) treatment. This study aimed to compare the intraprocedural ablation characteristics of two cryoballoons, Arctic Front Advance Pro™ (AFA-Pro, Medtronic) and POLARx™ (Boston Scientific). METHODS AND RESULTS: In this retrospective single-center study, 230 symptomatic paroxysmal or persistent AF patients underwent CB ablation with either AFA-Pro or POLARx. Propensity-score matching resulted in two cohorts of 114 patients each. Baseline and procedural characteristics were comparable between both CBs. POLARx achieved lower minimal temperatures (e.g., left superior pulmonary vein, LSPV: AFA-Pro - 49.0 °C vs. POLARx - 59.5 °C) and lower temperatures at time-to-isolation (TTI). Additionally, POLARx reached lower temperatures faster, as evidenced by lower temperatures after 40 and 60 s, and a larger mean temperature change between 20 and 40 s. POLARx also had a greater area under the curve below 0 °C and a longer thawing phase. Both CBs achieved comparable high rates of final PV-isolation. TTI, minimal esophagus temperature, and first-pass isolation rates were similar between groups. Periprocedural complications, including phrenic nerve injuries, were comparable. Troponin levels in the left atrium were elevated with both systems. Values and change in troponin were numerically higher in the POLARx group (delta troponin: AFA-Pro 36.3 (26.4, 125.4) ng/L vs. POLARx 104.9 (49.5, 122.2) ng/L), p = 0.077). CONCLUSION: AFA-Pro and POLARx are both highly effective and safe CB systems for PVI. POLARx exhibited significant faster and lower freezing characteristics, and numerically higher troponin levels might indicate greater myocardial injury. However, these differences did not translate into improved performance, procedural efficiency, or safety.

2.
Int J Cardiol Heart Vasc ; 44: 101168, 2023 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-36620202

RESUMEN

Aims: Na+/Ca2+ exchanger (NCX) upregulation in cardiac diseases like heart failure promotes as an independent proarrhythmic factor early and delayed afterdepolarizations (EADs/DADs) on the single cell level. Consequently, NCX inhibition protects against EADs and DADs in isolated cardiomyocytes. We here investigate, whether these promising cellular in vitro findings likewise apply to an in vivo setup. Methods/Results: Programmed ventricular stimulation (PVS) and isoproterenol were applied to a murine heterozygous NCX-knockout model (KO) to investigate ventricular arrhythmia initiation and perpetuation compared to wild-type (WT). KO displayed a reduced susceptibility towards isoproterenol-induced premature ventricular complexes. During PVS, initiation of single or double ectopic beats was similar between KO and WT. But strikingly, perpetuation of ventricular tachycardia (VT) was significantly increased in KO (animals with VT - KO: 82 %; WT: 47 %; p = 0.0122 / median number of VTs - KO: 4.5 (1.0, 6.25); WT: 0.0 (0.0, 4.0); p = 0.0039). The median VT duration was prolonged in KO (in s; KO: 0.38 (0.19, 0.96); WT: 0.0 (0.0, 0.60); p = 0.0239). The ventricular refractory period (VRP) was shortened in KO (in ms; KO: 15.1 ± 0.7; WT: 18.7 ± 0.7; p = 0.0013). Conclusions: Not the initiation, but the perpetuation of provoked whole-heart in vivo ventricular arrhythmia was increased in KO. As a potential mechanism, we found a significantly reduced VRP, which may promote perpetuation of reentrant ventricular arrhythmia. On a translational perspective, the antiarrhythmic concept of therapeutic NCX inhibition seems to be ambivalent by protecting from initiating afterdepolarizations but favoring arrhythmia perpetuation in vivo at least in a murine model.

3.
Transl Psychiatry ; 11(1): 164, 2021 03 15.
Artículo en Inglés | MEDLINE | ID: mdl-33723234

RESUMEN

Psychosocial stress is one of the main environmental factors contributing to the development of psychiatric disorders. In humans and rodents, chronic stress is associated with elevated inflammatory responses, indicated by increased numbers of circulating myeloid cells and activation of microglia, the brain-resident immune cells. The endocannabinoid system (ECS) regulates neuronal and endocrine stress responses via the cannabinoid receptor 1 (CB1). CB1-deficient mice (Cnr1-/-) are highly sensitive to stress, but if this involves altered inflammatory responses is not known. To test this, we exposed Cnr1+/+ and Cnr1-/- mice to chronic social defeat stress (CSDS). Cnr1-/- mice were extremely sensitive to a standard protocol of CSDS, indicated by an increased mortality rate. Therefore, a mild CSDS protocol was established, which still induced a behavioural phenotype in susceptible Cnr1-/- mice. These mice also showed altered glucocorticoid levels after mild CSDS, suggesting dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis. Mild CSDS induced weak myelopoiesis in the periphery, but no recruitment of myeloid cells to the brain. In contrast, mild CSDS altered microglial activation marker expression and morphology in Cnr1-/- mice. These microglial changes correlated with the severity of the behavioural phenotype. Furthermore, microglia of Cnr1-/- mice showed increased expression of Fkbp5, an important regulator of glucocorticoid signalling. Overall, the results confirm that CB1 signalling protects the organism from the physical and emotional harm of social stress and implicate endocannabinoid-mediated modulation of microglia in the development of stress-related pathologies.


Asunto(s)
Microglía , Derrota Social , Animales , Ratones , Ratones Endogámicos C57BL , Sistema Hipófiso-Suprarrenal , Receptor Cannabinoide CB1/genética , Receptores de Cannabinoides , Estrés Psicológico
4.
PLoS One ; 15(3): e0228913, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32126091

RESUMEN

BACKGROUND: Mutations in the human desmin gene (DES) cause autosomal-dominant and -recessive cardiomyopathies, leading to heart failure, arrhythmias, and AV blocks. We analyzed the effects of vascular pressure overload in a patient-mimicking p.R349P desmin knock-in mouse model that harbors the orthologue of the frequent human DES missense mutation p.R350P. METHODS AND RESULTS: Transverse aortic constriction (TAC) was performed on heterozygous (HET) DES-p.R349P mice and wild-type (WT) littermates. Echocardiography demonstrated reduced left ventricular ejection fraction in HET-TAC (WT-sham: 69.5 ± 2.9%, HET-sham: 64.5 ± 4.7%, WT-TAC: 63.5 ± 4.9%, HET-TAC: 55.7 ± 5.4%; p<0.01). Cardiac output was significantly reduced in HET-TAC (WT sham: 13088 ± 2385 µl/min, HET sham: 10391 ± 1349µl/min, WT-TAC: 8097 ± 1903µl/min, HET-TAC: 5793 ± 2517µl/min; p<0.01). Incidence and duration of AV blocks as well as the probability to induce ventricular tachycardias was highest in HET-TAC. We observed reduced mtDNA copy numbers in HET-TAC (WT-sham: 12546 ± 406, HET-sham: 13526 ± 781, WT-TAC: 11155 ± 3315, HET-TAC: 8649 ± 1582; p = 0.025), but no mtDNA deletions. The activity of respiratory chain complexes I and IV showed the greatest reductions in HET-TAC. CONCLUSION: Pressure overload in HET mice aggravated the clinical phenotype of cardiomyopathy and resulted in mitochondrial dysfunction. Preventive avoidance of pressure overload/arterial hypertension in desminopathy patients might represent a crucial therapeutic measure.


Asunto(s)
Sustitución de Aminoácidos , Bloqueo Atrioventricular/fisiopatología , Cardiomiopatías/fisiopatología , Desmina/genética , Animales , Bloqueo Atrioventricular/genética , Cardiomiopatías/genética , Variaciones en el Número de Copia de ADN , ADN Mitocondrial/genética , Modelos Animales de Enfermedad , Femenino , Técnicas de Sustitución del Gen , Heterocigoto , Humanos , Masculino , Ratones , Volumen Sistólico
7.
Herzschrittmacherther Elektrophysiol ; 30(4): 330-335, 2019 Dec.
Artículo en Alemán | MEDLINE | ID: mdl-31696309

RESUMEN

Catheter ablation of cardiac arrhythmias has evolved over the years and has become a cornerstone in the modern treatment of various supraventricular and ventricular arrhythmias. The goal of ablation is to permanently damage myocardium that is critically involved in the individual arrhythmia mechanism. Different catheters and forms of energy are available. Radiofrequency (RF) ablation is most common. Application of an alternating current at the catheter tip induces heating of tissue and, thus, leads to ablation of a targeted arrhythmogenic substrate. High temperatures (>70 °C at the catheter tip and >95 °C within the tissue) bear the risk of coagulum formation and steam pops and should be avoided, which limits power application. The evolution of irrigated RF ablation catheters enables the transfer of more power to the tissue and thereby increases the dimensions of the lesions. Cryoablation represents a valuable alternative. Cooling of tissue to -80 °C causes the intra- and extracellular formation of ice crystals, finally resulting in a dense circumscribed scar. The cryomapping procedure grants improved surveillance of the safety of ablation. Cryoenergy is very popular for pulmonary vein isolation (PVI) using the cryoballoon. In addition to the laser balloon that is established for PVI, ultrasound, microwaves, and stereotactic irradiation complete the arsenal.


Asunto(s)
Ablación por Catéter , Fibrilación Atrial , Criocirugía , Humanos , Venas Pulmonares
9.
Circulation ; 140(13): 1061-1069, 2019 09 24.
Artículo en Inglés | MEDLINE | ID: mdl-31466479

RESUMEN

BACKGROUND: Atrial arrhythmias are common in patients with implantable cardioverter-defibrillator (ICD). External shocks and internal cardioversion through commanded ICD shock for electrical cardioversion are used for rhythm-control. However, there is a paucity of data on efficacy of external versus internal cardioversion and on the risk of lead and device malfunction. We hypothesized that external cardioversion is noninferior to internal cardioversion for safety, and superior for successful restoration of sinus rhythm. METHODS: Consecutive patients with ICD undergoing elective cardioversion for atrial arrhythmias at 13 centers were randomized in 1:1 fashion to either internal or external cardioversion. The primary safety end point was a composite of surrogate events of lead or device malfunction. Conversion of atrial arrhythmia to sinus rhythm was the primary efficacy end point. Myocardial damage was studied by measuring troponin release in both groups. RESULTS: N=230 patients were randomized. Shock efficacy was 93% in the external cardioversion group and 65% in the internal cardioversion group (P<0.001). Clinically relevant adverse events caused by external or internal cardioversion were not observed. Three cases of pre-existing silent lead malfunction were unmasked by internal shock, resulting in lead failure. Troponin release did not differ between groups. CONCLUSIONS: This is the first randomized trial on external vs internal cardioversion in patients with ICDs. External cardioversion was superior for the restoration of sinus rhythm. The unmasking of silent lead malfunction in the internal cardioversion group suggests that an internal shock attempt may be reasonable in selected ICD patients presenting for electrical cardioversion. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov. Unique identifier: NCT03247738.


Asunto(s)
Arritmias Cardíacas/terapia , Fibrilación Atrial/terapia , Desfibriladores Implantables , Cardioversión Eléctrica/métodos , Anciano , Anciano de 80 o más Años , Falla de Equipo , Femenino , Humanos , Masculino , Persona de Mediana Edad , Riesgo
10.
Arch Med Sci ; 15(4): 845-856, 2019 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-31360179

RESUMEN

INTRODUCTION: Cardiac resynchronization therapy combined with an implantable cardioverter defibrillator (CRT-D) is widely applied in heart failure patients. Sufficient data on arrhythmia and defibrillator therapies during long-term follow-up of more than 4 years are lacking and data on mortality are conflicting. We aimed to characterize the occurrence of ventricular arrhythmia, respective defibrillator therapies and mortality for several years following CRT-D implantation or upgrade. MATERIAL AND METHODS: Eighty-eight patients with ischemic (ICM) or non-ischemic dilated cardiomyopathy (DCM) and at least one CRT-D replacement were included in this study and analyzed for incidence of non-sustained ventricular tachycardia (NSVT), defibrillator shocks, anti-tachycardia pacing (ATP) and mortality. RESULTS: ICM was the underlying disease in 59%, DCM in 41% of patients. During a mean follow-up of 76.4 ±24.8 months the incidence of appropriate defibrillator therapies (shock or ATP) was 46.6% and was elevated in ICM compared to DCM patients (57.7% vs. 30.6%, respectively; p = 0.017). Kaplan-Meier analysis revealed significantly higher ICD therapy-free survival rates in DCM patients (p = 0.031). Left ventricular ejection fraction, NSVT per year and ICM (vs. DCM) were independent predictors of device intervention. The ICM patients showed increased mortality compared to DCM patients, with cumulative all-cause mortality at 9 years of follow-up of 45.4% and 10.6%, respectively. Chronic renal failure, peripheral artery disease and chronic obstructive pulmonary disease were independent predictors of mortality. CONCLUSIONS: The clinical course of patients with ICM and DCM treated with CRT-D differs significantly during long-term follow-up, with increased mortality and incidence of ICD therapies in ICM patients.

11.
PLoS One ; 14(2): e0208301, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-30763348

RESUMEN

BACKGROUND: Clinical and experimental data give evidence that transplantation of stem and progenitor cells in myocardial infarction could be beneficial, although the underlying mechanism has remained elusive. Ventricular tachyarrhythmia is the most frequent and potentially lethal complication of myocardial infarction, but the impact of mono nuclear cells on the incidence of ventricular arrhythmia is still not clear. OBJECTIVE: We aimed to characterize the influence of splenic mononuclear cell populations on ventricular arrhythmia after myocardial infarction. METHODS: We assessed electrical vulnerability in vivo in mice with left ventricular cryoinfarction 14 days after injury and intramyocardial injection of specific subpopulations of mononuclear cells (MNCs) (CD11b-positive cells, Sca-1-positive cells, early endothelial progenitor cells (eEPCs)). As positive control group we used embryonic cardiomyocytes (eCMs). Epicardial mapping was performed for analysing conduction velocities in the border zone. Left ventricular function was quantified by echocardiography and left heart catheterization. RESULTS: In vivo pacing protocols induced ventricular tachycardia (VT) in 30% of non-infarcted mice. In contrast, monomorphic or polymorphic VT could be evoked in 94% of infarcted and vehicle-injected mice (p<0.01). Only transplantation of eCMs prevented post-infarction VT and improved conduction velocities in the border zone in accordance to increased expression of connexin 43. Cryoinfarction resulted in a broad aggravation of left ventricular function. All transplanted cell types augmented left ventricular function to a similar extent. CONCLUSIONS: Transplantation of different MNC populations after myocardial infarction improves left ventricular function similar to effects of eCMs. Prevention of inducible ventricular arrhythmia is only seen after transplantation of eCMs.


Asunto(s)
Arritmias Cardíacas/terapia , Infarto/terapia , Leucocitos Mononucleares/fisiología , Infarto del Miocardio/terapia , Animales , Arritmias Cardíacas/metabolismo , Antígeno CD11b/metabolismo , Conexina 43/metabolismo , Células Progenitoras Endoteliales/metabolismo , Mapeo Epicárdico/métodos , Infarto/metabolismo , Leucocitos Mononucleares/metabolismo , Proteínas de la Membrana/metabolismo , Ratones , Infarto del Miocardio/metabolismo , Miocitos Cardíacos/metabolismo , Miocitos Cardíacos/fisiología , Taquicardia Ventricular/metabolismo , Taquicardia Ventricular/terapia , Función Ventricular Izquierda/fisiología
13.
Artif Organs ; 43(7): 656-665, 2019 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-30589446

RESUMEN

Endoluminal left atrial appendage occlusion is an emerging therapy to treat patients suffering from atrial fibrillation with contraindications against oral anticoagulation. Different occlusion devices have been introduced into the clinical setting while comparative studies between the devices are sparse. This in vitro study compares several endoluminal left atrial appendage occlusion systems regarding 2 mechanical properties: radial (RF) and tug force (TF). Seven different occluder systems of various sizes (24 in total) underwent testing throughout their recommended sizing range. RF was measured in a commercial RF tester. TF was assessed according to a recently published bench test. RF increased with compression of the devices: The LAmbre 2228 device exerted the highest RF (8.6 N) at maximum compression of 16 mm. The lowest RF of 0.1 N was exhibited by the 27 mm Occlutech occluder at minimal compression. The highest TFs were exerted by the WaveCrest devices at maximum compression with 4.6 and 3.6 N for the 22 mm and the 27 mm device, respectively. The lowest TFs were measured for the first-generation Occlutech devices, particularly for the 24 mm device with 1.1 N at maximum compression and 0.4 N at minimum compression. A strong positive correlation was found between the number of hooks per millimeter circumference of an occluder and its tug force (r = 0.87, P < 0.01). The analysis revealed device stability to be more dependent on anchoring structures than on RF. The wide range of mechanical properties makes comparison of current LAA occluders difficult and emphasizes the need for standardized preclinical testing to prompt clinical compatibility.


Asunto(s)
Apéndice Atrial/cirugía , Dispositivo Oclusor Septal , Fibrilación Atrial/cirugía , Humanos , Fenómenos Mecánicos , Diseño de Prótesis , Implantación de Prótesis
14.
Sci Rep ; 8(1): 13618, 2018 09 11.
Artículo en Inglés | MEDLINE | ID: mdl-30206274

RESUMEN

To determine the pre-procedural value of different fibrotic biomarkers and comprehensive cardiac magnetic resonance (CMR) for the prediction of poor response to ablation therapy in patients with atrial fibrillation (AF). Left atrial (LA) late gadolinium enhancement (LGE) and native LA T1 relaxation times were assessed using CMR. Plasma levels of relaxin, myeloperoxidase and serum levels of matrix metalloproteinase (MMP)-mediated cardiac specific titin fragmentation and MMP-mediated type IV collagen degradation were obtained. Poor outcome was defined by the recurrence of AF during 1-year follow-up. 61 patients were included in final analysis. Twenty (32.8%) patients had recurrence of AF. Patients with a recurrence of AF had a higher percentage of LA LGE (26.7 ± 12.5% vs. 17.0 ± 7.7%; P < 0.001), higher LA T1 relaxation times (856.7 ± 112.2 ms vs. 746.8 ± 91.0 ms; P < 0.001) and higher plasma levels of relaxin (0.69 ± 1.34 pg/ml vs. 0.37 ± 0.88 pg/ml; P = 0.035). In the multivariate Cox regression analysis, poor ablation outcome was best predicted by advanced LGE stage (hazard ratio (HR):5.487; P = 0.001) and T1 relaxation times (HR:1.007; P = 0.001). Pre-procedural CMR is a valuable tool for prediction of poor response to catheter ablation therapy in patients with AF. It offers various imaging techniques for outcome prediction and might be valuable for a better patient selection prior to ablation therapy.


Asunto(s)
Fibrilación Atrial/diagnóstico por imagen , Fibrilación Atrial/fisiopatología , Fibrosis/diagnóstico por imagen , Fibrosis/fisiopatología , Adulto , Anciano , Anciano de 80 o más Años , Fibrilación Atrial/sangre , Fibrilación Atrial/terapia , Ablación por Catéter/efectos adversos , Colágeno Tipo IV/sangre , Conectina/sangre , Medios de Contraste/administración & dosificación , Femenino , Fibrosis/sangre , Fibrosis/terapia , Gadolinio/administración & dosificación , Atrios Cardíacos/diagnóstico por imagen , Atrios Cardíacos/fisiopatología , Humanos , Imagen por Resonancia Magnética , Masculino , Metaloproteinasas de la Matriz/sangre , Persona de Mediana Edad , Peroxidasa/sangre , Modelos de Riesgos Proporcionales , Relaxina/sangre
15.
Ann Biomed Eng ; 46(9): 1337-1347, 2018 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-29797140

RESUMEN

The aim of this study was to establish in vitro bench-tests of left atrial appendage occlusion (LAAo) devices regarding tug force, radial force and sealing capacity. Two LAAo devices, namely the WATCHMAN™ and the Occlutech®, of three different sizes underwent testing in novel dedicated in vitro setups. Radial force was assessed in a commercial radial force tester. At baseline, tug force of the WATCHMAN™ was significantly higher when compared to Occlutech® for all devices. Repeated resheathing resulted in a reduction of device-diameter in the WATCHMAN™ devices of max. 7.9%, whereas diameters of Occlutech® occluders remained unchanged. Tug force was not significantly impacted by resheathing in both devices. At baseline, sealing capacity in a bench-test using silicone LAA-models did not differ between the devices. Resheathing lead to an in vitro loss of sealing capacity of the WATCHMAN™ devices, increasing with resheathing and resulting in a max. peridevice leak of 91.1 ± 7.9%. Radial force was higher for the Occlutech® devices and decreased for WATCHMAN™ occluders after resheathing. The WATCHMAN™ occluder series showed progressive deformation, increased peridevice leakage and decreased radial force after resheathing, presumably as a result of diameter reduction. Tug force of the WATCHMAN™ was not impaired by resheathing and was significantly higher than that of the Occlutech® device.


Asunto(s)
Apéndice Atrial/cirugía , Dispositivo Oclusor Septal , Animales , Aorta/cirugía , Bovinos , Diseño de Equipo
16.
PLoS One ; 13(4): e0195631, 2018.
Artículo en Inglés | MEDLINE | ID: mdl-29634776

RESUMEN

BACKGROUND: In patients with liver cirrhosis, cardiac dysfunction is frequent and is associated with increased morbidity and mortality. Cardiac dysfunction in cirrhosis seems to be linked to autonomic dysfunction. This study investigates the role of autonomic dysfunction assessed by Heart Rate Turbulence (HRT) analyses in patients with liver cirrhosis. METHODS AND PATIENTS: Inclusion criteria was (1) diagnosis of cirrhosis by clinical, imaging or biopsy and (2) evaluation by standard 12-lead-ECG and 24h holter monitoring and (3) at least 3 premature ventricular contractions. The exclusion criterion was presence of cardiac diseases, independent of liver cirrhosis. Biochemical parameters were analysed using standard methods. HRT was assessed using Turbulence onset (TO) and slope (TS). The endpoint was deterioration of liver cirrhosis defined as increased MELD and readmission for complications of liver cirrhosis. RESULTS: Out of 122 cirrhotic patients, 82 patients (63% male) with median Child score of 6 (range 5-12) and median MELD score of 10 (range 6-32) were included. Increasing Child score, INR and decreasing albumin were correlated with TO. In addition, decompensated patients with ascites showed more abnormal TO and TS. During the observation period, patients with more abnormal TO showed significantly higher rate of rising MELD Score at 6 months (p = 0.03). Nevertheless, at least in our collective HRT-parameters were not independent predictors of deterioration of cirrhosis. CONCLUSION: Parameters of HRT are closely associated with deterioration of cirrhosis and might be helpful in its prediction.


Asunto(s)
Frecuencia Cardíaca , Cirrosis Hepática/fisiopatología , Adulto , Anciano , Anciano de 80 o más Años , Enfermedad Crónica , Progresión de la Enfermedad , Electrocardiografía , Femenino , Humanos , Masculino , Persona de Mediana Edad , Adulto Joven
17.
J Interv Card Electrophysiol ; 52(2): 141-148, 2018 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-29574595

RESUMEN

PURPOSE: Congenital atrial septal defect (ASD) is associated with increased morbidity, whereas little is known about the rate of spontaneous closure, associated clinical and echocardiographic parameters, or complications of iatrogenic atrial septal defect (iASD) beyond 1 year of follow-up. Persistent iASD after transseptal puncture for PVI has been described in up to 38% of small cohorts of patients in short-term follow-up after transseptal puncture. We sought to investigate the course of iASD after single transseptal puncture for first pulmonary vein isolation (PVI) with cryoballoon, along with possible risk factors for persistent iASD. METHODS: After a first PVI with cryoballoon, 102 patients (64 ± 10 years, 64% male) underwent long-term clinical follow-up and comprehensive transthoracic and transesophageal echocardiographic study. RESULTS: Prevalence of iASD after PVI was 37% after 2.9 (1.6-4.9) years. No clinical complications or deterioration of echocardiographic parameters were associated with iASD. Lower left atrial appendage flow velocity was associated with higher risk of persistence of iASD (3.5% for every 1 cm/s decrease, p = 0.002). CONCLUSIONS: Despite a high rate of iASD after cryoballoon PVI in long-term follow-up, this was not associated with increased clinical complications. Lower LAA velocity was associated with higher risk of persistent iASD. Repeated routine echocardiographic follow-up may not be necessary in these patients.


Asunto(s)
Ablación por Catéter/efectos adversos , Criocirugía/efectos adversos , Defectos del Tabique Interatrial/etiología , Venas Pulmonares/cirugía , Anciano , Análisis de Varianza , Ablación por Catéter/métodos , Estudios de Cohortes , Criocirugía/métodos , Bases de Datos Factuales , Ecocardiografía/métodos , Ecocardiografía Transesofágica/métodos , Femenino , Estudios de Seguimiento , Alemania , Defectos del Tabique Interatrial/diagnóstico por imagen , Defectos del Tabique Interatrial/epidemiología , Hospitales Universitarios , Humanos , Enfermedad Iatrogénica/epidemiología , Incidencia , Masculino , Persona de Mediana Edad , Monitoreo Fisiológico , Análisis Multivariante , Modelos de Riesgos Proporcionales , Estudios Retrospectivos , Medición de Riesgo , Análisis de Supervivencia , Factores de Tiempo
18.
Cardiovasc Res ; 114(5): 713-723, 2018 04 01.
Artículo en Inglés | MEDLINE | ID: mdl-29293898

RESUMEN

Aims: The primary goal in the treatment of symptomatic atrial fibrillation/flutter (AF) is to restore sinus rhythm by cardioversion. Electrical shocks are highly effective, but have to be applied under analgo-sedation and can further harm the heart. In order to develop a novel pain-free and less harmful approach, we explored herein the optogenetic cardioversion by light-induced depolarization. Methods and results: Hearts from mice expressing Channelrhodopsin-2 (ChR2) and the AF-promoting loss-of-function Connexin 40 Ala96Ser mutation were explanted and perfused with low K+ Tyrode's solution and an atrial KATP-channel activator. This new protocol shortened atrial refractoriness as well as slowed atrial conduction and thereby enabled the induction of sustained AF. AF episodes could be terminated by epicardial illumination of the atria with focussed blue light (470 nm, 0.4 mW/mm2) with an efficacy of ∼97% (n = 17 hearts). In > 80% of cases, light directly terminated the AF episode with onset of illumination. Because similar illumination intensity was able to locally inhibit atrial activity, we propose that a light-induced block of electrical activity is responsible for reliable AF termination. The success rate was strongly depending on the illuminated area, applied light intensity and duration of illumination. Importantly, we were also able to demonstrate optogenetic termination of AF in vivo, using epicardial illumination through the open chest (n = 3 hearts). To point towards a translational potential, we systemically injected an adeno-associated virus to express ChR2 in wild type hearts. After 6-8 months, we found robust ChR2 expression in the atria, enabling light-mediated AF termination in six of seven mice tested. Conclusion: We provide the first evidence for optogenetic termination of atrial tachyarrhythmia in intact hearts from transgenic as well as wild type mice ex and in vivo. Thus, this report could lay the foundation for the development of implantable devices for pain-free termination of AF.


Asunto(s)
Fibrilación Atrial/terapia , Función Atrial , Atrios Cardíacos/fisiopatología , Frecuencia Cardíaca , Optogenética , Taquicardia Supraventricular/terapia , Potenciales de Acción , Animales , Fibrilación Atrial/genética , Fibrilación Atrial/metabolismo , Fibrilación Atrial/fisiopatología , Channelrhodopsins/genética , Channelrhodopsins/metabolismo , Conexinas/genética , Conexinas/metabolismo , Modelos Animales de Enfermedad , Femenino , Predisposición Genética a la Enfermedad , Atrios Cardíacos/metabolismo , Canales KATP/metabolismo , Masculino , Ratones Endogámicos C57BL , Ratones Transgénicos , Mutación , Fenotipo , Periodo Refractario Electrofisiológico , Taquicardia Supraventricular/genética , Taquicardia Supraventricular/metabolismo , Taquicardia Supraventricular/fisiopatología , Proteína alfa-5 de Unión Comunicante
19.
Int J Cardiol ; 250: 21-28, 2018 Jan 01.
Artículo en Inglés | MEDLINE | ID: mdl-29169754

RESUMEN

BACKGROUND: The peptide hormone relaxin-2 (RLX) exerts beneficial effects during myocardial ischemia, but functional data on lower-dose RLX in myocardial infarction (MI) is lacking. Therefore, we investigated the impact of 75µg/kg/d RLX treatment on electrical vulnerability and left ventricular function in a mouse model of MI. METHODS AND RESULTS: Standardized cryoinfarction of the left anterior ventricular wall was performed in mice. A two week treatment period with vehicle or RLX via subcutaneously implanted osmotic minipumps was started immediately after MI. The relaxin receptor RXFP1 was expressed on ventricular/atrial cardiomyocytes, myofibroblasts, macrophages and endothelial but not vascular smooth muscle cells of small coronary vessels. RLX treatment resulted in a significant reduction of ventricular tachycardia inducibility (vehicle: 91%, RLX: 18%, p<0.0001) and increased epicardial conduction velocity in the left ventricle and borderzone. Furthermore, left ventricular function following MI was improved in RLX treated mice (left ventricular ejection fraction; vehicle: 41.1±1.9%, RLX: 50.5±3.5%, p=0.04). Interestingly, scar formation was attenuated by RLX with decreased transcript expression of connective tissue growth factor. Transcript levels of the pro-inflammatory cytokines interleukin-6 and interleukin-1ß were upregulated in hearts of vehicle treated animals compared to mice without MI. Application of RLX attenuated this inflammatory response. In addition, macrophage infiltration was reduced in the borderzone of RLX treated mice. CONCLUSION: Treatment with lower-dose RLX in mice prevents post-infarction ventricular tachycardia due to attenuation of scar formation and cardiac inflammation. Therefore, RLX could be evaluated as new therapeutic option in the treatment of MI.


Asunto(s)
Antiinflamatorios/administración & dosificación , Arritmias Cardíacas/prevención & control , Cardiotónicos/administración & dosificación , Infarto del Miocardio/prevención & control , Relaxina/administración & dosificación , Animales , Arritmias Cardíacas/metabolismo , Arritmias Cardíacas/patología , Esquema de Medicación , Femenino , Fibrosis , Masculino , Ratones , Infarto del Miocardio/metabolismo , Infarto del Miocardio/patología
20.
Pacing Clin Electrophysiol ; 41(1): 22-27, 2018 01.
Artículo en Inglés | MEDLINE | ID: mdl-29211301

RESUMEN

BACKGROUND: Pulmonary vein isolation (PVI) has become a widely accepted therapy in patients suffering from symptomatic atrial fibrillation (AF). HYPOTHESIS: AF-free survival differs in patients with left common pulmonary vein (LCPV) after PVI with second-generation cryoballoon. METHODS: We included patients scheduled for first PVI for paroxysmal or persistent AF. Symptomatic and/or documented arrhythmia episodes (>30 seconds) were defined as AF recurrence, excluding a 3-month blanking period. RESULTS: We observed a LCPV in 37 of 270 consecutive patients (13.7%). Analyses were performed in a 1:1 propensity score matched cohort of 68 patients. During a median follow-up of 77.0 weeks, 37 patients (54.4%) had recurrent AF. The prevalence of LCPV was numerically higher in patients with AF recurrence (62.2% vs 35.5%, P  =  0.051) and Kaplan-Meier analysis showed lower AF-free survival in patients with existence of a LCPV (P  =  0.028). At 1-year follow-up, 70.6% of patients without versus 55.1% of patients with LCPV were free of AF. Multivariate Cox regression analysis revealed presence of a LCPV (hazard ratio [HR]: 2.996), chronic heart failure (HR: 3.423), and mitral regurgitation > I° (HR: 2.571) as predictors of AF recurrence. CONCLUSION: Patients with LCPV had significantly reduced AF-free survival after ablation with the second-generation cryoballoon, despite similar acutely successful PVIs.


Asunto(s)
Fibrilación Atrial/cirugía , Criocirugía/instrumentación , Venas Pulmonares/cirugía , Anciano , Fibrilación Atrial/diagnóstico por imagen , Angiografía Coronaria , Ecocardiografía , Femenino , Fluoroscopía , Alemania , Humanos , Masculino , Puntaje de Propensión , Recurrencia , Estudios Retrospectivos , Resultado del Tratamiento
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