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BACKGROUND: Exercise training safely and efficiently improves symptoms in patients with heart failure due to left ventricular dysfunction. However, studies in congenital heart disease with systemic right ventricle are scarce and results are controversial. In a randomised controlled study we investigated the effect of aerobic exercise training on exercise capacity and systemic right ventricular function in adults with d-transposition of the great arteries after atrial redirection surgery (28.2 ± 3.0 years after Mustard procedure). METHODS: 48 patients (31 male, age 29.3 ± 3.4 years) were randomly allocated to 24 weeks of structured exercise training or usual care. Primary endpoint was the change in maximum oxygen uptake (peak VO2). Secondary endpoints were systemic right ventricular diameters determined by cardiac magnetic resonance imaging (CMR). Data were analysed per intention to treat analysis. RESULTS: At baseline peak VO2 was 25.5 ± 4.7 ml/kg/min in control and 24.0 ± 5 ml/kg/min in the training group (p=0.3). Training significantly improved exercise capacity (treatment effect for peak VO2 3.8 ml/kg/min, 95% CI: 1.8 to 5.7; p=0.001), work load (p=0.002), maximum exercise time (p=0.002), and NYHA class (p=0.046). Systemic ventricular function and volumes determined by CMR remained unchanged. None of the patients developed signs of cardiac decompensation or arrhythmias while on exercise training. CONCLUSIONS: Aerobic exercise training did not detrimentally affect systemic right ventricular function, but significantly improved exercise capacity and heart failure symptoms. Aerobic exercise training can be recommended for patients following atrial redirection surgery to improve exercise capacity and to lessen or prevent heart failure symptoms. ( CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov #NCT00837603).
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Tolerancia al Ejercicio/fisiología , Ejercicio Físico/fisiología , Transposición de los Grandes Vasos/fisiopatología , Transposición de los Grandes Vasos/cirugía , Función Ventricular Derecha/fisiología , Adulto , Femenino , Estudios de Seguimiento , Humanos , Masculino , Transposición de los Grandes Vasos/terapiaRESUMEN
BACKGROUND: Patients with patent foramen ovale (PFO) and cryptogenic stroke are at risk of recurrence. Therapeutic regimens range from no treatment to anticoagulation treatment to surgical or interventional closure. However, long-term follow-up is only available for up to 4 years. METHODS: Among ~5,000 transesophageal echocardiographies in stroke/TIA-patients between 1988 and 1997, a PFO was found and considered a possible mediator for the neurological event in 97 patients. In these patients, the PFO was judged to be responsible for the neurological event. Patients with cardiac or other reasons for embolism were excluded. The therapy for stroke was chosen by the attending physician. Follow-up information was obtained through telephone interviews. RESULTS: Follow-up was available for 86 patients (89%) with a mean period of 15.4 years (range, 11.2-25.9 years). Thirteen patients (15%) suffered from recurrent ischemic events (7 TIAs, 5 strokes, 1 peripheral embolism) after a mean period of 4.9 years. Four patients died, not associated with recurrent thromboembolism. The risk of recurrence was increased over the entire length of the mean follow-up period. The occurrence of recurrent events was not associated with differences in baseline data, the presence of ASA, PFO size or the chosen treatment. CONCLUSION: In patients with paradoxical embolism, recurrent ischemic events are frequent despite medical therapy. These events are not limited to the early years after the index event; this long-term follow-up revealed a risk of occurrence over the entire follow-up. These patients have a sustained risk of recurrence, requiring lifetime protection, which should be considered in tailoring individual therapeutic strategies.
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Embolia Paradójica/epidemiología , Foramen Oval Permeable/complicaciones , Accidente Cerebrovascular/epidemiología , Tromboembolia/epidemiología , Adulto , Ecocardiografía Transesofágica , Femenino , Estudios de Seguimiento , Humanos , Ataque Isquémico Transitorio/epidemiología , Ataque Isquémico Transitorio/etiología , Masculino , Persona de Mediana Edad , Recurrencia , Factores de Riesgo , Accidente Cerebrovascular/etiología , Tromboembolia/etiología , Factores de TiempoRESUMEN
OBJECTIVES: The aim of this study was to investigate whether nebivolol has added effects on left ventricular (LV) dysfunction and remodeling early after myocardial infarction (MI) beyond its ß1-receptor-blocking properties. BACKGROUND: Nebivolol is a third-generation selective ß1-adrenoreceptor antagonist that stimulates endothelial cell nitric oxide (NO) production and prevents vascular reduced nicotinamide adenine dinucleotide phosphate (NADPH) oxidase activation. Both endothelial NO synthase-derived NO production and NADPH oxidase activation are critical modulators of LV dysfunction early after MI. METHODS: Mice with extensive anterior MI (n = 90) were randomized to treatment with nebivolol (10 mg/kg/day), metoprolol-succinate (20 mg/kg/day), or placebo for 30 days starting on day 1 after surgery. RESULTS: Infarct size was similar among the groups. Both ß1-adrenergic receptor antagonists caused a similar decrease in heart rate. Nebivolol therapy improved endothelium-dependent vasorelaxation and increased early endothelial progenitor cells 4 weeks after MI compared with metoprolol and placebo. Nebivolol, but not metoprolol, inhibited cardiac NADPH oxidase activation after MI, as detected by electron spin resonance spectroscopy analysis. Importantly, nebivolol, but not metoprolol, improved LV dysfunction 4 weeks after MI (LV ejection fraction: nebivolol vs. metoprolol vs. placebo: 32 ± 4% vs. 17 ± 6% vs. 19 ± 4%; nebivolol vs. metoprolol: p < 0.05) and was associated with improved survival 4 weeks post-MI compared with placebo. Nebivolol had a significantly more pronounced inhibitory effect on cardiomyocyte hypertrophy after MI compared with metoprolol. CONCLUSIONS: Nebivolol improves LV dysfunction and survival early after MI likely beyond the effects provided by conventional ß1-receptor blockade. Nebivolol induced effects on NO-mediated endothelial function, early endothelial progenitor cells and inhibition of myocardial NADPH oxidase likely contribute to these beneficial effects of nebivolol early after MI.
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Antagonistas de Receptores Adrenérgicos beta 1/uso terapéutico , Benzopiranos/uso terapéutico , Etanolaminas/uso terapéutico , Células Madre Hematopoyéticas/fisiología , Infarto del Miocardio/tratamiento farmacológico , Neovascularización Fisiológica/fisiología , Disfunción Ventricular Izquierda/tratamiento farmacológico , Animales , Células Cultivadas , Endotelio Vascular/efectos de los fármacos , Endotelio Vascular/fisiología , Células Madre Hematopoyéticas/efectos de los fármacos , Humanos , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Infarto del Miocardio/complicaciones , Infarto del Miocardio/fisiopatología , Nebivolol , Neovascularización Fisiológica/efectos de los fármacos , Distribución Aleatoria , Ratas , Factores de Tiempo , Disfunción Ventricular Izquierda/etiología , Disfunción Ventricular Izquierda/fisiopatologíaRESUMEN
BACKGROUND: Prevalence of patent foramen ovale (PFO) with detectable right-to-left shunt is higher in young adults with transient ischemic attack (TIA) and stroke compared to the general population. So far, published series included different occluder systems, various indications and regimens of postprocedural anticoagulation. In our experience, occluder systems may be associated with an increased prevalence of thrombus formation, which has also reported by other groups. The aim of the present study was to evaluate the follow-up results after implantation of the Amplatzer® occluder in patients with PFO using a consistent anticoagulation regimen. METHODS AND RESULTS: One-hundred and fourteen patients with PFO (60 men; age: 47 ± 13 years) and ≥1 thromboembolic event were included. Other causes for embolism were excluded. PFO-closure was successful in all patients. All patients were treated with aspirin (100 mg/day) and clopidogrel (75 mg/day) for 6 months. TEE was repeated at a mean of 10.3 months. Mean clinical follow-up period was 18 ± 9 months. After a mean of 10 months, no patient had either a significant residual shunt nor a suspected thrombus formation on the occluder. During follow-up, 5 patients suffered from neurological events (1 stroke, 2 TIAs, 2 epileptic seizures), though complete closure of the PFO was documented by TEE. One patient suffered from bleeding complications (upper GI-bleeding). CONCLUSION: Percutaneous closure of PFO in symptomatic patients by Amplatzer® occluder represents an effective therapy with a low incidence of peri-interventional complications and recurrent thromboembolism. Thrombus formations on the occluder system were not detected in this cohort.
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Cateterismo Cardíaco/métodos , Embolia Paradójica/terapia , Foramen Oval Permeable/terapia , Dispositivo Oclusor Septal/estadística & datos numéricos , Aspirina/uso terapéutico , Cateterismo Cardíaco/instrumentación , Clopidogrel , Ecocardiografía Transesofágica , Embolia Paradójica/diagnóstico por imagen , Embolia Paradójica/cirugía , Femenino , Foramen Oval Permeable/diagnóstico por imagen , Foramen Oval Permeable/cirugía , Humanos , Ataque Isquémico Transitorio , Masculino , Persona de Mediana Edad , Inhibidores de Agregación Plaquetaria/uso terapéutico , Estudios Prospectivos , Factores de Riesgo , Accidente Cerebrovascular , Encuestas y Cuestionarios , Tromboembolia , Ticlopidina/análogos & derivados , Ticlopidina/uso terapéuticoRESUMEN
BACKGROUND: Laparoscopic sleeve gastrectomy (LSG) is generally considered a restrictive procedure. However, studies with nuclear medicine techniques have demonstrated that gastric motility changes occur following LSG. These motility changes could represent complementary mechanisms of weight loss. Therefore, we analyzed the stomach motility before and after LSG by means of dynamic MRI. METHODS: In this prospective pilot study, five female patients with a mean BMI of 51.6 kg/m(2) underwent MRI 1 day before LSG and 6 days and 6 months after LSG. Dynamic steady-state free precession sequences were used to analyze the gastric motility after ingestion of 500 ml water with a temporal resolution of 0.86 s. Axial image stacks were also repeatedly acquired to determine the intragastric fluid volume over time. RESULTS: Mean excess body mass index loss was 60.6% after 6 months. Dynamic analysis showed that antral propulsive peristalsis was preserved immediately after surgery and during follow-up, but fold speed increased significantly from 2.7 mm/s before LSG to 4.4 mm/s after 6 months. The sleeve itself remained without recognizable peristalsis in three patients and showed only uncoordinated or passive motion in two patients. Consequently, the fluid transport through the sleeve was markedly delayed, whereas the antrum showed accelerated propulsion with the emptying half-time decreasing from 16.5 min preoperatively to 7.9 min 6 months after surgery. CONCLUSIONS: Owing to the LSG procedure, the stomach is functionally divided into a sleeve without propulsive peristalsis and an accelerated antrum. Accelerated emptying seems to be caused by faster peristaltic folds.
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Gastrectomía , Motilidad Gastrointestinal/fisiología , Imagen por Resonancia Cinemagnética , Obesidad Mórbida/fisiopatología , Estómago/fisiopatología , Adulto , Ingestión de Alimentos , Femenino , Humanos , Laparoscopía , Persona de Mediana Edad , Obesidad Mórbida/cirugía , Peristaltismo/fisiología , Proyectos Piloto , Estudios ProspectivosRESUMEN
OBJECTIVES: To evaluate the relation of echocardiographic parameters of diastolic function, exercise capacity (expressed as peakVO(2)) and NT-proBNP in patients with transposition of the great arteries (TGA) and Mustard procedure. METHODS: Diastolic function was determined by measuring tricuspid flow velocities (Ea/Aa ratio), isovolumic relaxation time (IVRT), and deceleration time (DT). E/Ea ratios were calculated. For assessment of systolic function, CMR was applied. RESULTS: E/A (r = 0.07, p = 0.66), E/Ea medial (r = 0.03, p = 0.84), E/Ea lateral (r = -0.01, p = 0.92), IVRT (r = -0.13, p = 0.44), and DT (r = -0.05, p = 0.76) were not correlated with peakVO(2). NT-proBNP showed a significant correlation with IVRT (r = 0.44, p = 0.004) and Ea/Aa medial (r = -0.34, p = 0.025). No correlation was found between RV systolic function and peakVO(2) (r = 0.07, p = 0.63). CONCLUSIONS: Exercise capacity in patients with TGA and Mustard procedure is not related to echocardiographic parameters of diastolic function. NT-proBNP is associated with selected echocardiographic parameters of diastolic function.
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Procedimientos Quirúrgicos Cardíacos/métodos , Tolerancia al Ejercicio/fisiología , Péptido Natriurético Encefálico/sangre , Fragmentos de Péptidos/sangre , Transposición de los Grandes Vasos , Adulto , Biomarcadores/sangre , Diástole/fisiología , Ecocardiografía , Prueba de Esfuerzo , Femenino , Humanos , Masculino , Consumo de Oxígeno/fisiología , Sístole/fisiología , Transposición de los Grandes Vasos/diagnóstico por imagen , Transposición de los Grandes Vasos/fisiopatología , Transposición de los Grandes Vasos/cirugía , Función Ventricular Derecha/fisiologíaRESUMEN
BACKGROUND: Symptomatic severe aortic stenosis is associated with increased mortality and morbidity. Early identification of these patients by echocardiography is crucial. We conducted this study to evaluate a handheld ultrasound device (HCU) in patients with suspected severe aortic stenosis (AS) in comparison to a standard echocardiography device (SE). METHODS: A HCU (Vivid I; GE Healthcare) and a SE device (Philips iE 33) were used to evaluate 50 consecutive patients with suspected severe AS. Two consecutive echocardiographic studies were performed by two experienced and blinded examiners using HCU and SE device. AS was graded by mean transaortic pressure, aortic valve area (AVA), and indexed AVA (AVA adjusted for body surface area). RESULTS: Mean difference for mean transaortic gradient, AVA and indexed AVA for the SE and HCU device were 1.28 mmHg (-0.70 to 3.26 mmHg), -0.02 cm(2) (-0.06 to 0.01 cm(2)), and -0.01 cm(2)/m(2) (-0.03 to 0.01 cm(2)/m(2)), respectively. Discrepancies between both devices were not associated with misinterpretation of the degree of AS. CONCLUSION: Our study demonstrates that HCU can be used to evaluate patients with suspected AS. (ECHOCARDIOGRAPHY 2010;27:481-486).
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Estenosis de la Válvula Aórtica/diagnóstico por imagen , Ecocardiografía Doppler/instrumentación , Anciano , Diseño de Equipo , Femenino , Humanos , Masculino , Reproducibilidad de los Resultados , TransductoresRESUMEN
BACKGROUND: In patients with myocardial infarction, high serum levels of interleukin-6 cytokines predict a poor outcome. The common receptor of interleukin-6 cytokines, glycoprotein-130 (gp130), signals via janus kinase/signal transducer and activator of transcription (STAT), cytoplasmic protein tyrosine phosphatase/extracellular signal-regulated kinase, and phosphoinositide-3-kinase/Akt pathways, and the regulation of these pathways depends at least in part on the gp130 tyrosine-757 residue. By analyzing cardiomyocyte-specific gp130(Y757F) mutant mice, we investigated the effect of disturbed gp130 signaling after myocardial infarction. METHODS AND RESULTS: The cardiomyocyte-restricted alpha-myosin heavy chain-Cre-recombinase-loxP system was used to generate mice with gp130(Y757F) mutant cardiomyocytes (alphaMHC-Cre(tg/-);gp130(fl/Y757F) [Y(757)F]); all other cells carried at least 1 functional gp130 gene, ensuring normal gp130 signaling. Y(757)F mice displayed normal cardiac function and morphology at 3 months of age comparable to their nonmutant littermates. In response to myocardial infarction, Y(757)F mice displayed higher mortality associated with increased left ventricular rupture rate, sustained cardiac inflammation, and heart failure. These adverse effects were associated with prolonged and enhanced STAT3 activation and increased expression of interleukin-6 and of the complement-activating mannose-binding lectin C. Pharmacological inhibition of the complement system by cobra venom factor attenuated inflammation, prevented left ventricular rupture, and improved cardiac function in Y(757)F mice. Stronger effects were observed with a genetic reduction of STAT3 (STAT3(flox/+)) restricted to cardiomyocytes in Y(757)F mice, which prevented extensive upregulation of interleukin-6, complement activation, and sustained inflammation and lowered left ventricular rupture rate, heart failure, and mortality in subacute myocardial infarction. CONCLUSIONS: Impaired downregulation of gp130-mediated STAT3 activation in subacute infarction promotes cardiac inflammation, adverse remodeling, and heart failure, suggesting a potential causative role of high interleukin-6 serum levels after myocardial infarction.
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Receptor gp130 de Citocinas/metabolismo , Infarto del Miocardio/metabolismo , Miocarditis/metabolismo , Factor de Transcripción STAT3/metabolismo , Animales , Receptor gp130 de Citocinas/genética , Regulación hacia Abajo/genética , Humanos , Interleucina-6/sangre , Interleucina-6/genética , Ratones , Ratones Mutantes , Mutación Missense , Infarto del Miocardio/genética , Infarto del Miocardio/patología , Miocarditis/genética , Miocarditis/patología , Miocitos Cardíacos/metabolismo , Miocitos Cardíacos/patología , Rotura Espontánea/genética , Rotura Espontánea/metabolismo , Factor de Transcripción STAT3/genéticaRESUMEN
AIMS: We have recently observed that intracoronary autologous bone marrow cell (BMC)-transfer improves parameters of diastolic function in patients after acute myocardial infarction at 6 and 18 months. There is no clinical study addressing the long-term effect of BMC transfer on diastolic function. Therefore, we conducted a 5-year follow-up of the BOOST trial to evaluate a sustained benefit on echocardiographic parameters on diastolic function. METHODS AND RESULTS: After successful primary percutaneous coronary intervention (PCI) for acute ST-elevation MI, patients were randomized to a control (n = 28) or BMC transfer group (n = 28). Echocardiography was performed at 4.5 +/- 1.5 days after PCI, at 6, 18, and 60 months. Diastolic function was determined by measuring transmitral flow velocities (E/A ratio), diastolic myocardial velocities (E(a)/A(a) ratio), isovolumic relaxation time (IVRT), and deceleration time (DT). All analyses were performed in a blinded fashion. There was an overall treatment effect of BMC transfer on E/A (0.25 +/- 0.10; 95% CI 0.05-0.44; P = 0.01). E/A ratio was significantly lower at 6 (Control 0.90 +/- 0.07; BMC 1.23 +/- 0.14; P = 0.03) and 18 months (Control 0.87+/-0.04; BMC 1.13 +/- 0.09; P = 0.01) in the control group, whereas E/A ratio was not different at 60 months between both groups (Control 0.90 +/- 0.06; BMC 1.05 +/- 0.07; P = 0.12). We found no overall effect of BMC transfer on E(a)/A(a) ratio (0.21 +/- 0.14; 95% CI -0.03 to 0.46; P = 0.09), DT (-12 +/- 11 ms; 95% CI -21 to 28; P = 0.75), IVRT -6 +/- 7 ms; 95% CI -9 to 19; P = 0.43), and E/E(a) ratio (0.58 +/- 0.88; 95% CI -1.18 to 2.34; P = 0.51). CONCLUSION: Intracoronary autologous BMC transfer provides an overall treatment effect on echocardiographic parameters of diastolic function in patients after AMI. However, this effect is basically related to an early improvement of parameters of diastolic function without a sustained effect on long-term follow-up.
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Trasplante de Médula Ósea , Infarto del Miocardio/terapia , Disfunción Ventricular Izquierda/diagnóstico por imagen , Análisis de Varianza , Angioplastia Coronaria con Balón , Intervalos de Confianza , Diástole , Ecocardiografía Doppler , Humanos , Imagen por Resonancia Cinemagnética , Persona de Mediana Edad , Infarto del Miocardio/diagnóstico por imagen , Factores de Tiempo , Resultado del Tratamiento , Disfunción Ventricular Izquierda/terapiaRESUMEN
As the first reliable prosthetic heart valve to be introduced, the Starr-Edwards ball valve prosthesis has gained worldwide clinical acceptance. Although very few instances have been described of valve durability exceeding 30 years, the case is reported of a patient with a well-functioning Starr-Edwards ball valve prosthesis in the aortic position, 43 years after implantation.
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Válvula Aórtica , Prótesis Valvulares Cardíacas , Anciano de 80 o más Años , Estudios de Seguimiento , Humanos , Masculino , Diseño de PrótesisRESUMEN
AIMS: We assessed whether a single intracoronary infusion of autologous bone marrow cells (BMCs) can have a sustained impact on left ventricular ejection fraction (LVEF) in patients after ST-elevation myocardial infarction (STEMI). In the BOne marrOw transfer to enhance ST-elevation infarct regeneration (BOOST) trial, 60 patients with STEMI and successful percutaneous coronary intervention were randomized to a control and a cell therapy group. As previously reported, BMC transfer led to an improvement of LVEF by 6.0% at 6 months (P = 0.003) and 2.8% at 18 months (P = 0.27). METHODS AND RESULTS: Left ventricular ejection fraction and clinical status were re-assessed in all surviving patients after 61 +/- 11 months. Major adverse cardiac events occurred with similar frequency in both groups. When compared with baseline, LVEF assessed by magnetic resonance imaging at 61 months decreased by 3.3 +/- 9.5% in the control group and by 2.5 +/- 11.9% in the BMC group (P = 0.30). Patients with an infarct transmurality > median appeared to benefit from BMC transfer throughout the 61-month study period (P = 0.040). CONCLUSION: A single intracoronary application of BMCs does not promote a sustained improvement of LVEF in STEMI patients with relatively preserved systolic function. It is conceivable that a subgroup of patients with more transmural infarcts may derive a sustained benefit from BMC therapy. However, this needs to be tested prospectively in a randomized trial.
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Trasplante de Médula Ósea/métodos , Infarto del Miocardio/terapia , Adulto , Anciano , Estudios de Seguimiento , Humanos , Angiografía por Resonancia Magnética , Persona de Mediana Edad , Infarto del Miocardio/fisiopatología , Volumen Sistólico/fisiología , Trasplante Autólogo , Resultado del Tratamiento , Disfunción Ventricular Izquierda/etiología , Disfunción Ventricular Izquierda/terapiaRESUMEN
Mitral regurgitation (MR) is the second most frequent valve disease in Europe. In addressing the current therapy for MR, it is useful to distinguish primary from secondary or functional MR. In primary MR, there is derangement of the mitral valve itself causing left ventricular volume overload and left ventricular dysfunction. By contrast, in secondary MR, the valve and its components are typically normal and MR is related to changes of annular size (dilatation) and papillary muscle displacement due to left ventricular damage caused by myocardial infarction or dilated cardiomyopathy.In primary MR, mitral valve repair or replacement is the first-line therapy. In secondary MR, the best management includes standard medical therapy for heart failure and cardiac resynchronization therapy in selected patients. Since there is no evidence from randomized studies that surgery improves mortality, this approach may only be considered in patients who remain symptomatic despite optimal medical therapy or in patients undergoing coronary revascularization.
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Estimulación Cardíaca Artificial/métodos , Cardiotónicos/uso terapéutico , Procedimientos Quirúrgicos Cardiovasculares/métodos , Insuficiencia de la Válvula Mitral/diagnóstico , Insuficiencia de la Válvula Mitral/terapia , HumanosRESUMEN
PURPOSE: To integrate SMS (sliding multislice imaging technique for acquiring axial images during continuous table motion) into a high-resolution pelvic MRI protocol for additional staging of the entire abdomen within one examination. MATERIALS AND METHODS: Axial two-dimensional images were acquired during continuous table motion using a fat-saturated contrast-enhanced T1-weighted gradient echo sequence. Patients held their breath during the first 20 s of the examination and breathed normally afterward while data acquisition continued. Measurement parameters were adjusted to optimize image quality throughout the total field of view. The method was investigated in 22 patients with pelvic malignancies. Two readers independently compared SMS image quality to conventional abdominal MR images, generated by a stationary multi-breath-hold gradient echo sequence. RESULTS: Qualitative evaluation yielded high diagnostic value of SMS data in body regions with no or minor breathing motion, and in those acquired during the initial breath-hold. Image quality in the upper abdomen, retroperitoneum, and pelvis is reproducible and equivalent to stationary MRI. Interfering artifacts are related to the intestine in the mid-abdomen. CONCLUSION: SMS is a promising technique that may have the potential for a first-line abdominal staging tool in patients with pelvic malignancies.
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Imagen por Resonancia Magnética/métodos , Estadificación de Neoplasias/métodos , Neoplasias Pélvicas/patología , Abdomen , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Proyectos PilotoRESUMEN
BACKGROUND: Prevalence of patent foramen ovale (PFO) is higher in patients with paradoxical embolism and associated with increased risk for recurrent thromboembolic events. By percutaneous closure of PFO, surgical closure or permanent oral anticoagulation can be avoided. So far, published series included different occluder systems and various indications and regimens of postprocedural anticoagulation. The aim of the present study was to evaluate the short- and long-term results after implantation of the Starflex occluder in patients with PFO using an intensified anticoagulation regimen. METHODS AND RESULTS: 154 patients with PFO (94 men; age: 44 +/- 13 years) and >or=1 thromboembolic event were included. Other causes for embolism were excluded. PFO closure was successful in 147 patients (95.5%). All patients were treated with phenprocoumon (INR 2.5) and aspirin (100 mg/die) for 6 months. Transesophageal echocardiography (TEE) was repeated at 6 months. Mean clinical follow-up period was 26 +/- 18 months. After 6 months, five patients had a significant residual shunt, and five patients had suspected thrombus formation on the occluder. In three of these five patients, the occluder was surgically removed and foreign body reaction was noted. During follow-up, nine patients suffered from neurological events (two strokes, seven transient ischemic attacks [TIA]), though complete closure of the PFO was documented by TEE. Two patients died during follow-up; three patients had bleeding complications. CONCLUSION: Percutaneous closure of PFO in symptomatic patients by Starflex occluder represents an effective therapy with a low incidence of periinterventional complications and recurrent thromboembolism. However, thrombus formation at the occluder system may occur in some patients despite an aggressive anticoagulation regimen.
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Anticoagulantes/uso terapéutico , Cateterismo Cardíaco/métodos , Embolia Paradójica/prevención & control , Foramen Oval Permeable/terapia , Adulto , Aspirina/uso terapéutico , Cateterismo Cardíaco/instrumentación , Embolia Paradójica/complicaciones , Femenino , Foramen Oval Permeable/complicaciones , Foramen Oval Permeable/diagnóstico por imagen , Encuestas Epidemiológicas , Humanos , Masculino , Fenprocumón/uso terapéutico , Inhibidores de Agregación Plaquetaria/uso terapéutico , Prevalencia , Estudios Prospectivos , Factores de Riesgo , Prevención Secundaria , Encuestas y Cuestionarios , UltrasonografíaRESUMEN
BACKGROUND: Mice with a knockout (KO) of muscle LIM protein (MLP) exhibit many morphologic and clinical features of human cardiomyopathy. In humans, MLP-expression is downregulated both in ischemic and dilative cardiomyopathy. In this study, we investigated the effects of MLP on the electrophysiologic phenotype in vivo and on outward potassium currents. METHODS AND RESULTS: MLP-deficient (MLPKO) and wild-type (MLPWT) mice were subjected to long-term electrocardiogram (ECG) recording and in vivo electrophysiologic study. The whole-cell, patch-clamp technique was applied to measure voltage dependent outward K+ currents in isolated cardiomyocytes. Long-term ECG revealed a significant prolongation of RR mean (108 +/- 9 versus 99 +/- 5 ms), P (16 +/- 3 versus 14 +/- 1 ms), QRS (17 +/- 3 versus 13 +/- 1 ms), QT (68 +/- 8 versus 46 +/- 7 ms), QTc (66 +/- 6 versus 46 +/- 7 ms), JT (51 +/- 7 versus 34 +/- 7 ms), and JTc (49 +/- 5 versus 33 +/- 7 ms) in MLPKO versus MLPWT mice (P < .05). During EP study, QT (80 +/- 8 versus 58 +/- 7 ms), QTc (61 +/- 6 versus 45 +/- 5 ms), JT (62 +/- 9 versus 43 +/- 6 ms), and JTc (47 +/- 5 versus 34 +/- 5 ms) were also significantly prolonged in MLPKO mice (P < .05). Nonsustained VT was inducible in 9/16 MLPKO versus 2/15 MLPWT mice (P < .05). Analysis of outward K+ currents in revealed a significantly reduced density of the slowly inactivating outward K+ current IK, slow in MLPKO mice (11 +/- 5 pA/pF versus 18 +/- 7 pA/pF; P < .05). CONCLUSION: Mice with KO of MLP exhibit significant prolongation of atrial and ventricular conduction and an increased ventricular vulnerability. A reduction in repolarizing outward K+ currents may be responsible for these alterations.
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Canales de Potasio de Tipo Rectificador Tardío/fisiología , Proteínas Musculares/deficiencia , Disfunción Ventricular Izquierda/metabolismo , Animales , Electrofisiología , Femenino , Proteínas con Dominio LIM , Masculino , Ratones , Ratones Noqueados , Proteínas Musculares/genética , Disfunción Ventricular Izquierda/genética , Función Ventricular/fisiologíaRESUMEN
Accumulating evidence suggests a critical role of increased reactive oxygen species production for left ventricular (LV) remodeling and dysfunction after myocardial infarction (MI). An increased myocardial activity of the NAD(P)H oxidase, a major oxidant enzyme system, has been observed in human heart failure; however, the role of the NAD(P)H oxidase for LV remodeling and dysfunction after MI remains to be determined. MI was induced in wild-type (WT) mice (n=46) and mice lacking the cytosolic NAD(P)H oxidase component p47(phox) (p47(phox)-/- mice) (n=32). Infarct size was similar among the groups. NAD(P)H oxidase activity was markedly increased in remote LV myocardium of WT mice after MI as compared with sham-operated mice (83+/-8 versus 16.7+/-3.5 nmol of O(2)(-) x microg(-1) x min(-1); P<0.01) but not in p47(phox)-/- mice after MI (13.5+/-3.6 versus 15.5+/-3.5 nmol of O(2)(-) x microg(-1) x min(-1)), as assessed by electron-spin resonance spectroscopy using the spin probe CP-H. Furthermore, increased myocardial xanthine oxidase activity was observed in WT, but not in p47(phox)-/- mice after MI, suggesting NAD(P)H oxidase-dependent xanthine oxidase activation. Myocardial reactive oxygen species production was increased in WT mice, but not in p47(phox)-/- mice, after MI. LV cavity dilatation and dysfunction 4 weeks after MI were markedly attenuated in p47(phox)-/- mice as compared with WT mice, as assessed by echocardiography (LV end-diastolic diameter: 4.5+/-0.2 versus 6.3+/-0.3 mm, P<0.01; LV ejection fraction, 35.8+/-2.5 versus 22.6+/-4.4%, P<0.05). Furthermore, cardiomyocyte hypertrophy, apoptosis, and interstitial fibrosis were substantially reduced in p47(phox)-/- mice as compared with WT mice. Importantly, the survival rate was markedly higher in p47(phox)-/- mice as compared with WT mice after MI (72% versus 48%; P<0.05). These results suggest a pivotal role of NAD(P)H oxidase activation and its subunit p47(phox) for LV remodeling/dysfunction and survival after MI. The NAD(P)H oxidase system represents therefore a potential novel therapeutic target to prevent cardiac failure after MI.
Asunto(s)
Infarto del Miocardio/fisiopatología , Miocardio/metabolismo , NADPH Oxidasas/metabolismo , Disfunción Ventricular Izquierda/enzimología , Remodelación Ventricular , Animales , Apoptosis/genética , Modelos Animales de Enfermedad , Progresión de la Enfermedad , Espectroscopía de Resonancia por Spin del Electrón , Activación Enzimática/genética , Inhibidores Enzimáticos/farmacología , Pruebas de Función Cardíaca , Metaloproteinasa 2 de la Matriz/metabolismo , Ratones , Ratones Noqueados , Infarto del Miocardio/enzimología , Infarto del Miocardio/patología , Miocardio/enzimología , NADPH Oxidasas/genética , Óxido Nítrico/metabolismo , Superóxidos/metabolismo , Tasa de Supervivencia , Disfunción Ventricular Izquierda/genética , Remodelación Ventricular/efectos de los fármacos , Remodelación Ventricular/genética , Xantina Oxidasa/antagonistas & inhibidores , Xantina Oxidasa/metabolismoRESUMEN
Postpartum cardiomyopathy (PPCM) is a disease of unknown etiology and exposes women to high risk of mortality after delivery. Here, we show that female mice with a cardiomyocyte-specific deletion of stat3 develop PPCM. In these mice, cardiac cathepsin D (CD) expression and activity is enhanced and associated with the generation of a cleaved antiangiogenic and proapoptotic 16 kDa form of the nursing hormone prolactin. Treatment with bromocriptine, an inhibitor of prolactin secretion, prevents the development of PPCM, whereas forced myocardial generation of 16 kDa prolactin impairs the cardiac capillary network and function, thereby recapitulating the cardiac phenotype of PPCM. Myocardial STAT3 protein levels are reduced and serum levels of activated CD and 16 kDa prolactin are elevated in PPCM patients. Thus, a biologically active derivative of the pregnancy hormone prolactin mediates PPCM, implying that inhibition of prolactin release may represent a novel therapeutic strategy for PPCM.
Asunto(s)
Cardiomiopatías/metabolismo , Catepsina D/metabolismo , Complicaciones Cardiovasculares del Embarazo/metabolismo , Prolactina/metabolismo , Trastornos Puerperales/metabolismo , Factor de Transcripción STAT3/metabolismo , Animales , Bromocriptina/farmacología , Bromocriptina/uso terapéutico , Cardiomiopatías/prevención & control , Catepsina D/sangre , Modelos Animales de Enfermedad , Femenino , Trasplante de Corazón , Humanos , Hipertrofia Ventricular Izquierda , Lactancia/sangre , Lipoproteínas LDL/sangre , Masculino , Ratones , Ratones Noqueados , Miocardio/metabolismo , Miocardio/patología , Miocitos Cardíacos/metabolismo , Neovascularización Patológica , Estrés Oxidativo , Fragmentos de Péptidos/sangre , Periodo Posparto/metabolismo , Embarazo , Complicaciones Cardiovasculares del Embarazo/prevención & control , Prolactina/antagonistas & inhibidores , Prolactina/sangre , Trastornos Puerperales/prevención & control , Factor de Transcripción STAT3/sangre , Factor de Transcripción STAT3/genéticaAsunto(s)
Transfusión de Eritrocitos/efectos adversos , Cardiopatías/etiología , Hemocromatosis/etiología , Deferoxamina/uso terapéutico , Resultado Fatal , Femenino , Insuficiencia Cardíaca/etiología , Hemocromatosis/tratamiento farmacológico , Humanos , Persona de Mediana Edad , Sideróforos/uso terapéuticoRESUMEN
We report on a case of a mobile left atrial thrombus formation on an atrial septal defect occluder system (28 mm StarFLEX-Occluder) despite 6 months of postprocedural anticoagulation with phenprocoumon and platelet antiaggregation with aspirin in a 69-year-old woman. The closure was performed because of a significant left to right atrial shunt (Qp/Qs 1.8) with enlargement of the right atrial and ventricular cavities and impairment of right ventricular function in the presence of persistent atrial fibrillation and chronic heart failure (NYHA II-III). The 6-month follow up by transoesophageal echocardiography (TEE) revealed the floating thrombus located at the left atrial side of the occluder.
Asunto(s)
Oclusión con Balón/instrumentación , Embolización Terapéutica/efectos adversos , Defectos del Tabique Interatrial/cirugía , Prótesis e Implantes/efectos adversos , Tromboembolia/etiología , Anciano , Embolización Terapéutica/instrumentación , Femenino , Defectos del Tabique Interatrial/diagnóstico por imagen , Humanos , Tromboembolia/diagnóstico por imagen , UltrasonografíaRESUMEN
We are presenting a case of floating left and right atrial formations on an atrial septal defect occluder system (23mm StarFLEX)-Occluder) initially supposed to be thrombotic appositions in a 57-year-old man. The closure was performed on the background of left hemispheric stroke and atrial septal aneurysm (ASA) with patent foramen ovale (PFO). The suspect structures were detected in the 6-month follow-up by transesophageal echocardiography (TEE). The patient underwent a successful surgical explantation of the closure device and closure of the patent foramen ovale (PFO) using a pericardial patch. The pathological evaluation of the biatrial device associated appositions revealed hytrophic heart muscle tissue with perifocal scarring and purulent abscess-forming, granulating and foam-cell including inflammatory foreign body reaction instead of the expected thrombus formation.