RESUMEN
BACKGROUND: Myocardial infarction is a frequent cause of out-of-hospital cardiac arrest. However, the benefits of early coronary angiography and revascularization in resuscitated patients without electrocardiographic evidence of ST-segment elevation are unclear. METHODS: In this multicenter trial, we randomly assigned 554 patients with successfully resuscitated out-of-hospital cardiac arrest of possible coronary origin to undergo either immediate coronary angiography (immediate-angiography group) or initial intensive care assessment with delayed or selective angiography (delayed-angiography group). All the patients had no evidence of ST-segment elevation on postresuscitation electrocardiography. The primary end point was death from any cause at 30 days. Secondary end points included a composite of death from any cause or severe neurologic deficit at 30 days. RESULTS: A total of 530 of 554 patients (95.7%) were included in the primary analysis. At 30 days, 143 of 265 patients (54.0%) in the immediate-angiography group and 122 of 265 patients (46.0%) in the delayed-angiography group had died (hazard ratio, 1.28; 95% confidence interval [CI], 1.00 to 1.63; P = 0.06). The composite of death or severe neurologic deficit occurred more frequently in the immediate-angiography group (in 164 of 255 patients [64.3%]) than in the delayed-angiography group (in 138 of 248 patients [55.6%]), for a relative risk of 1.16 (95% CI, 1.00 to 1.34). Values for peak troponin release and for the incidence of moderate or severe bleeding, stroke, and renal-replacement therapy were similar in the two groups. CONCLUSIONS: Among patients with resuscitated out-of-hospital cardiac arrest without ST-segment elevation, a strategy of performing immediate angiography provided no benefit over a delayed or selective strategy with respect to the 30-day risk of death from any cause. (Funded by the German Center for Cardiovascular Research; TOMAHAWK ClinicalTrials.gov number, NCT02750462.).
Asunto(s)
Angiografía Coronaria , Electrocardiografía , Paro Cardíaco Extrahospitalario/diagnóstico por imagen , Anciano , Reanimación Cardiopulmonar , Causas de Muerte , Enfermedad Coronaria/complicaciones , Enfermedad Coronaria/diagnóstico por imagen , Femenino , Humanos , Estimación de Kaplan-Meier , Tiempo de Internación , Masculino , Persona de Mediana Edad , Enfermedades del Sistema Nervioso/etiología , Paro Cardíaco Extrahospitalario/complicaciones , Paro Cardíaco Extrahospitalario/mortalidad , Paro Cardíaco Extrahospitalario/terapia , Infarto del Miocardio con Elevación del ST/diagnóstico por imagen , Factores de Tiempo , Tiempo de TratamientoRESUMEN
BACKGROUND: Quantitative flow ratio (QFR) is a novel, software-based method to evaluate the physiology of coronary lesions. The aim of this study was to compare QFR with the established invasive measurements of coronary blood flow using instantaneous wave-free ratio (iFR) or resting full-cycle ratio (RFR) in daily cathlab routine. METHODS: 102 patients with stable coronary artery disease and a coronary stenosis of 40%-90% were simultaneously assessed with QFR and iFR or RFR. QFR-computation was performed by two certified experts using the appropriate software (QAngio XA 3D 3.2). RESULTS: QFR showed a significant correlation (r = 0.75, p < 0.001) to iFR and RFR. The area under the receiver curve for all measurements was 0.93 (95% confidence interval, 0.87-0.98) for QFR compared to iFR or RFR. QFR based assessment required less time with a median of 501 s (IQR 421-659 s) compared to iFR or RFR which required a median of 734 s to obtain the result (IQR 512-967 s; p < 0.001). The median use of contrast medium was similar with 21 mL (IQR 16-30 mL) for the QFR-based and 22 mL (IQR 15-35 mL) for the iFR- or RFR-based diagnostic. QFR diagnostic required less radiation. The median dose area product for QFR was 307cGycm2 (IQR 151-429 cGycm2 ) compared to 599 cGycm2 (IQR 345-1082 cGycm2 ) for iFR or RFR, p < 0.001. CONCLUSION: QFR measurements of coronary artery blood flow correlate with iFR or RFR measurements and are associated with shorter procedure times and reduced radiation dose.
Asunto(s)
Enfermedad de la Arteria Coronaria , Estenosis Coronaria , Reserva del Flujo Fraccional Miocárdico , Humanos , Angiografía Coronaria/métodos , Valor Predictivo de las Pruebas , Resultado del Tratamiento , Enfermedad de la Arteria Coronaria/diagnóstico por imagen , Estenosis Coronaria/diagnóstico por imagen , Cateterismo Cardíaco , Vasos Coronarios/diagnóstico por imagen , Índice de Severidad de la EnfermedadRESUMEN
BACKGROUND: The role of thrombolytic treatment in patients with intermediate high-risk pulmonary embolism (IHR-PE) remains controversial. OBJECTIVES: In this study, we assessed whether systemic thrombolysis decreases hemodynamic decompensation and mortality in a cohort of unselected patients with IHR compared with patients with conventional anticoagulation. METHODS: Between January 2014 and December 2018, 137 patients with IHR-PE were identified among 539 consecutive patients treated for symptomatic PE. In 35 patients (25.5%), systemic thrombolysis was used. Propensity score matching was performed based on 17 pretreatment variables. The primary outcome was hemodynamic decompensation, defined by systolic hypotension, need for catecholamines or signs of end-organ hypoperfusion, and all-cause mortality during hospitalization. Secondary outcomes, such as 1-year survival, and safety outcomes, such as bleeding events, were analyzed. RESULTS: The effects of systemic thrombolysis and anticoagulation were compared in 55 matched patients with IHR-PE (systemic thrombolysis n = 21; anticoagulation n = 34). Thrombolysis was associated with a reduction (0% vs. 31%; p = 0.004) of the primary outcome during hospitalization and a 1-year survival benefit (100% vs. 83.2%; p = 0.036). Severe bleeding events occurred in 4.8% vs. 0% (p = 0.382) and moderate bleeding was observed in 14.3% vs. 7.1% (p = 0.359) in patients with thrombolysis compared with anticoagulation, respectively. CONCLUSIONS: Thrombolysis was associated with a significant reduction of the combined endpoint of hemodynamic decompensation and death during hospitalization and lower all-cause mortality after 1 year in an unselected group of patients with IHR-PE. Further studies are required to improve the therapy of IHR-PE and to identify the subgroup of patients that might benefit from thrombolytic therapy.
Asunto(s)
Embolia Pulmonar , Anticoagulantes/uso terapéutico , Fibrinolíticos/efectos adversos , Hemorragia/complicaciones , Humanos , Puntaje de Propensión , Embolia Pulmonar/diagnóstico , Terapia Trombolítica/efectos adversos , Resultado del TratamientoRESUMEN
BACKGROUND: In acute myocardial infarction complicated by cardiogenic shock the use of mechanical circulatory support devices remains controversial and data from randomized clinical trials are very limited. Extracorporeal life support (ECLS) - venoarterial extracorporeal membrane oxygenation - provides the strongest hemodynamic support in addition to oxygenation. However, despite increasing use it has not yet been properly investigated in randomized trials. Therefore, a prospective randomized adequately powered clinical trial is warranted. STUDY DESIGN: The ECLS-SHOCK trial is a 420-patient controlled, international, multicenter, randomized, open-label trial. It is designed to compare whether treatment with ECLS in addition to early revascularization with percutaneous coronary intervention or alternatively coronary artery bypass grafting and optimal medical treatment is beneficial in comparison to no-ECLS in patients with severe infarct-related cardiogenic shock. Patients will be randomized in a 1:1 fashion to one of the two treatment arms. The primary efficacy endpoint of ECLS-SHOCK is 30-day mortality. Secondary outcome measures such as hemodynamic, laboratory, and clinical parameters will serve as surrogate endpoints for prognosis. Furthermore, a longer follow-up at 6 and 12 months will be performed including quality of life assessment. Safety endpoints include peripheral ischemic vascular complications, bleeding and stroke. CONCLUSIONS: The ECLS-SHOCK trial will address essential questions of efficacy and safety of ECLS in addition to early revascularization in acute myocardial infarction complicated by cardiogenic shock.
Asunto(s)
Oxigenación por Membrana Extracorpórea , Infarto del Miocardio/terapia , Revascularización Miocárdica/métodos , Puente de Arteria Coronaria/métodos , Oxigenación por Membrana Extracorpórea/efectos adversos , Oxigenación por Membrana Extracorpórea/métodos , Fibrinolíticos/uso terapéutico , Humanos , Infarto del Miocardio/complicaciones , Infarto del Miocardio/mortalidad , Pronóstico , Estudios Prospectivos , Calidad de Vida , Tamaño de la Muestra , Choque Cardiogénico/etiología , Choque Cardiogénico/mortalidadRESUMEN
Patients experiencing out-of-hospital cardiac arrest (OHCA) without ST-segment elevation are a heterogenic group with a variety of underlying causes. Up to one-third of patients display a significant coronary lesion compatible with myocardial infarction as OHCA trigger. There are no randomized data on patient selection and timing of invasive coronary angiography after admission. METHODS AND RESULTS: The TOMAHAWK trial randomly assigns 558 patients with return of spontaneous circulation after OHCA with no obvious extracardiac origin of cardiac arrest and no ST-segment elevation/left bundle-branch block on postresuscitation electrocardiogram to either immediate coronary angiography or initial intensive care assessment with delayed/selective angiography in a 1:1 ratio. The primary end point is 30-day all-cause mortality. Secondary analyses will be performed with respect to initial rhythm, electrocardiographic patterns, myocardial infarction as underlying cause, neurological outcome, as well as clinical and laboratory markers. Clinical follow-up will be performed at 6 and 12 months. Safety end points include bleeding and stroke. CONCLUSION: The TOMAHAWK trial will address the unresolved issue of timing and general indication of angiography after OHCA without ST-segment elevation.
Asunto(s)
Reanimación Cardiopulmonar/métodos , Angiografía Coronaria/métodos , Electrocardiografía , Paro Cardíaco Extrahospitalario/diagnóstico , Tiempo de Tratamiento , Triaje/métodos , Causas de Muerte/tendencias , Europa (Continente)/epidemiología , Estudios de Seguimiento , Humanos , Paro Cardíaco Extrahospitalario/mortalidad , Paro Cardíaco Extrahospitalario/terapia , Estudios Prospectivos , Tasa de Supervivencia/tendencias , Factores de TiempoRESUMEN
BACKGROUND: A well-developed coronary collateral circulation provides a potential source of blood supply in coronary artery disease. However, the prognostic importance and functional relevance of coronary collaterals is controversial with the association between exercise training and collateral growth still unclear. METHODS AND RESULTS: This prospective, open-label study randomly assigned 60 patients with significant coronary artery disease (fractional flow reserve ≤0.75) to high-intensity exercise (group A, 20 patients) or moderate-intensity exercise (group B, 20 patients) for 4 weeks or to a control group (group C, 20 patients). The primary end point was the change of the coronary collateral flow index (CFI) after 4 weeks. Analysis was based on the intention to treat. After 4 weeks, baseline CFI increased significantly by 39.4% in group A (from 0.142±0.07 at beginning to 0.198±0.09 at 4 weeks) in comparison with 41.3% in group B (from 0.143±0.06 to 0.202±0.09), whereas CFI in the control group remained unchanged (0.7%, from 0.149±0.09 to 0.150±0.08). High-intensity exercise did not lead to a greater CFI than moderate-intensity training. After 4 weeks, exercise capacity, Vo2 peak and ischemic threshold increased significantly in group A and group B in comparison with group C with no difference between group A and group B. CONCLUSIONS: A significant improvement in CFI was demonstrated in response to moderate- and high-intensity exercise performed for 10 hours per week. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01209637.
Asunto(s)
Circulación Colateral/fisiología , Enfermedad Coronaria/terapia , Vasos Coronarios/fisiopatología , Terapia por Ejercicio , Adulto , Anciano , Angina Inestable/etiología , Angina Inestable/terapia , Aorta/fisiopatología , Presión Arterial , Cateterismo Cardíaco/efectos adversos , Presión Venosa Central , Enfermedad Coronaria/fisiopatología , Embolia Aérea/etiología , Prueba de Esfuerzo , Terapia por Ejercicio/efectos adversos , Terapia por Ejercicio/métodos , Tolerancia al Ejercicio , Femenino , Vena Femoral/fisiopatología , Reserva del Flujo Fraccional Miocárdico , Humanos , Masculino , Persona de Mediana Edad , Consumo de Oxígeno , Estudios ProspectivosRESUMEN
RATIONALE: High-density lipoprotein (HDL) exerts endothelial-protective effects via stimulation of endothelial cell (EC) nitric oxide (NO) production. This function is impaired in patients with cardiovascular disease. Protective effects of exercise training (ET) on endothelial function have been demonstrated. OBJECTIVE: This study was performed to evaluate the impact of ET on HDL-mediated protective effects and the respective molecular pathways in patients with chronic heart failure (CHF). METHODS AND RESULTS: HDL was isolated from 16 healthy controls (HDL(healthy)) and 16 patients with CHF-NYHA-III (HDL(NYHA-IIIb)) before and after ET, as well as from 8 patients with CHF-NYHA-II (HDL(NYHA-II)). ECs were incubated with HDL, and phosphorylation of eNOS-Ser(1177), eNOS-Thr(495), PKC-ßII-Ser(660), and p70S6K-Ser(411) was evaluated. HDL-bound malondialdehyde and HDL-induced NO production by EC were quantified. Endothelial function was assessed by flow-mediated dilatation. The proteome of HDL particles was profiled by shotgun LC-MS/MS. Incubation of EC with HDL(NYHA-IIIb) triggered a lower stimulation of phosphorylation at eNOS-Ser(1177) and a higher phosphorylation at eNOS-Thr(495) when compared with HDL(healthy). This was associated with lower NO production of EC. In addition, an elevated activation of p70S6K, PKC-ßII by HDL(NYHA-IIIb), and a higher amount of malondialdehyde bound to HDL(NYHA-IIIb) compared with HDL(healthy) was measured. In healthy individuals, ET had no effect on HDL function, whereas ET of CHF-NYHA-IIIb significantly improved HDL function. A correlation between changes in HDL-induced NO production and flow-mediated dilatation improvement by ET was evident. CONCLUSIONS: These results demonstrate that HDL function is impaired in CHF and that ET improved the HDL-mediated vascular effects. This may be one mechanism how ET exerts beneficial effects in CHF.
Asunto(s)
Prueba de Esfuerzo/métodos , Insuficiencia Cardíaca/terapia , Lipoproteínas HDL/fisiología , Acondicionamiento Físico Humano/fisiología , Anciano , Células Cultivadas , Enfermedad Crónica , Estudios de Cohortes , Femenino , Estudios de Seguimiento , Insuficiencia Cardíaca/sangre , Insuficiencia Cardíaca/fisiopatología , Humanos , Lipoproteínas HDL/sangre , Masculino , Persona de Mediana EdadRESUMEN
Background: Red blood cell distribution width (RDW) is calculated in every blood count test and reflects variability in erythrocyte size. High levels mirror dysregulated erythrocyte homeostasis and have been associated with clonal hematopoiesis as well as higher mortality in several conditions.We aimed to determine the impact of preprocedural RDW levels on functional outcomes after transcatheter aortic valve implantation (TAVI). Methods: In this single-center retrospective study, we analyzed 176 consecutive patients receiving TAVI between 2017 and 2021. RDW upper limit of normal was < 15 %. Patients were stratified according to preprocedural RDW as having normal or elevated values. We assessed all-cause-mortality and a composite endpoint comprising cardiovascular/ valve-related mortality and cardiovascular, valve-related and heart failure hospitalization at 1 year. Results: 43 patients (24.4 %) had RDW ≥ 15 %. There were significant baseline differences between groups (Society of Thoracic Surgeons - Predicted Risk of Mortality score 3.18 %[interquartile range 1.87-5.47] vs. 6.63 %[4.12-10.54] p < 0.001; hemoglobin 13.2 g/dL[11.8-14.1] vs. 10.4 g/dL[9.8-12.2], p < 0.001, RDW-normal vs. RDW-high, respectively). Age was not distinct (80.2 years [77.5-84.1] vs 81.2[71.3-84.7], p = 0.78). 1-year-all-cause mortality was not different (7.9 % vs. 9.4 %, p = 0.79). The RDW-high group showed markedly higher NT-proBNP levels after 1 year (647 ng/ml[283-1265] vs. 1893 ng/ml[744-5109], p = 0.005), and experienced more clinical endpoints (hazard ratio 2.57[1.28-5.16] for the composite endpoint, p = 0.006). RDW remained an independent predictor of the composite endpoint when accounting for all baseline differences in multivariable regression. Conclusion: Elevated preprocedural RDW identifies patients at risk for impaired functional outcome after TAVI and may represent a useful low-cost parameter to guide intensity of outpatient surveillance strategies.
RESUMEN
Echocardiography in patients with atrial fibrillation is challenging due to the varying heart rate. Thus, the topic of this expert proposal focuses on an obvious gap in the current recommendations about diagnosis and treatment of atrial fibrillation (AF)-the peculiarities and difficulties of echocardiographic imaging. The assessment of systolic and diastolic function-especially in combination with valvular heart diseases-by echocardiography can basically be done by averaging the results of echocardiographic measurements of the respective parameters or by the index beat approach, which uses a representative cardiac cycle for measurement. Therefore, a distinction must be made between the functionally relevant status, which is characterized by the averaging method, and the best possible hemodynamic status, which is achieved with the most optimal left ventricular (LV) filling according to the index beat method with longer previous RR intervals. This proposal focuses on left atrial and left ventricular function and deliberately excludes problems of echocardiography when assessing left atrial appendage in terms of its complexity. Echocardiography of the left atrial appendage is therefore reserved for its own expert proposal.
RESUMEN
BACKGROUND: Muscle wasting occurs in both chronic heart failure (CHF) and normal aging and contributes to exercise intolerance and increased morbidity/mortality. However, the molecular mechanisms of muscle atrophy in CHF and their interaction with aging are still largely unknown. We therefore measured the activation of the ubiquitin-proteasome system and the lysosomal pathway of intracellular proteolysis in muscle biopsies of CHF patients and healthy controls in two age strata and assessed the age-dependent effects of a 4-week endurance training program on the catabolic-anabolic balance. METHODS AND RESULTS: Sixty CHF patients (30 patients aged ≤55 years, mean age 46±5 years; 30 patients aged ≥65 years, mean age 72±5 years) and 60 healthy controls (30 subjects aged ≤55 years, mean age 50±5 years; 30 subjects aged ≥65 years, mean age 72±4 years) were randomized to 4 weeks of supervised endurance training or to a control group. Before and after the intervention, vastus lateralis muscle biopsies were obtained. The expressions of cathepsin-L and the muscle-specific E3 ligases MuRF-1 and MAFbx were measured by real-time polymerase chain reaction and confirmed by Western blot. At baseline, MuRF-1 expression was significantly higher in CHF patients versus healthy controls (mRNA: 624±59 versus 401±25 relative units; P=0.007). After 4 weeks of exercise training, MuRF-1 mRNA expression was reduced by -32.8% (P=0.02) in CHF patients aged ≤55 years and by -37.0% (P<0.05) in CHF patients aged ≥65 years. CONCLUSIONS: MuRF-1, a component of the ubiquitin-proteasome system involved in muscle proteolysis, is increased in the skeletal muscle of patients with heart failure. Exercise training results in reduced MuRF-1 levels, suggesting that it blocks ubiquitin-proteasome system activation and does so in both younger and older CHF patients. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00176319.
Asunto(s)
Envejecimiento/metabolismo , Ejercicio Físico/fisiología , Insuficiencia Cardíaca/metabolismo , Proteínas Musculares/metabolismo , Músculo Esquelético/metabolismo , Resistencia Física/fisiología , Ubiquitina-Proteína Ligasas/metabolismo , Anciano , Biopsia , Catepsina L/metabolismo , Enfermedad Crónica , Alemania/epidemiología , Insuficiencia Cardíaca/epidemiología , Insuficiencia Cardíaca/patología , Humanos , Persona de Mediana Edad , Músculo Esquelético/patología , Complejo de la Endopetidasa Proteasomal/metabolismo , ARN Mensajero/metabolismo , Proteínas Ligasas SKP Cullina F-box/metabolismo , Proteínas de Motivos Tripartitos , Ubiquitina/metabolismoRESUMEN
The case of a 71-year-old male with end stage heart failure and severe mitral regurgitation is presented, where percutaneous indirect mitral annuloplasty was performed. During device implantation in the coronary sinus the circumflex artery was compromised at two anatomic locations, while the mitral regurgitation was efficiently reduced. After weighing risks and alternative therapeutic options, stent implantation was chosen as bailout strategy to leave the device in place and retain the efficient MR reduction. The anatomical proximity of Cx and coronary sinus in the mitral valve plane bears the risk of circumflex artery damage during surgical and interventional mitral repair. Usually, a device exchange solves the problem of arterial flow limitation in most cases. While stent implantation remains off label use in this setting and should not be performed without critical evaluation, it has been performed successfully in similar clinical settings as well (e.g. artery stenosis by surgical suture).
Asunto(s)
Seno Coronario , Anuloplastia de la Válvula Mitral , Insuficiencia de la Válvula Mitral , Masculino , Humanos , Anciano , Insuficiencia de la Válvula Mitral/diagnóstico , Insuficiencia de la Válvula Mitral/cirugía , Insuficiencia de la Válvula Mitral/etiología , Vasos Coronarios/diagnóstico por imagen , Vasos Coronarios/cirugía , Válvula Mitral/diagnóstico por imagen , Válvula Mitral/cirugíaRESUMEN
Importance: Myocardial infarction is a frequent cause of out-of-hospital cardiac arrest (OHCA). The long-term effect of early coronary angiography on patients with OHCA with possible coronary trigger but no ST-segment elevation remains unclear. Objective: To compare the clinical outcomes of early unselective angiography with the clinical outcomes of a delayed or selective approach for successfully resuscitated patients with OHCA of presumed cardiac origin without ST-segment elevation at 1-year follow-up. Design, Setting, and Participants: The TOMAHAWK trial was a multicenter, international (Germany and Denmark), investigator-initiated, open-label, randomized clinical trial enrolling 554 patients between November 23, 2016, to September 20, 2019. Patients with stable return of spontaneous circulation after OHCA of presumed cardiac origin but without ST-segment elevation on the postresuscitation electrocardiogram were eligible for inclusion. A total of 554 patients were randomized to either immediate coronary angiography after hospital admission or an initial intensive care assessment with delayed or selective angiography after a minimum of 24 hours. All 554 patients were included in survival analyses during the follow-up period of 1 year. Secondary clinical outcomes were assessed only for participants alive at 1 year to account for the competing risk of death. Interventions: Early vs delayed or selective coronary angiography and revascularization if indicated. Main Outcomes and Measures: Evaluations in this secondary analysis included all-cause mortality after 1 year, as well as severe neurologic deficit, myocardial infarction, and rehospitalization for congestive heart failure in survivors at 1 year. Results: A total of 281 patients were randomized to the immediate angiography group and 273 to the delayed or selective group, with a median age of 70 years (IQR, 60-78 years). A total of 369 of 530 patients (69.6%) were male, and 268 of 483 patients (55.5%) had a shockable arrest rhythm. At 1 year, all-cause mortality was 60.8% (161 of 265) in the immediate angiography group and 54.3% (144 of 265) in the delayed or selective angiography group without significant difference between the treatment strategies, trending toward an increase in mortality with immediate angiography (hazard ratio, 1.25; 95% CI, 0.99-1.57; P = .05). For patients surviving until 1 year, the rates of severe neurologic deficit, myocardial infarction, and rehospitalization for congestive heart failure were similar between the groups. Conclusions and Relevance: This study found that a strategy of immediate coronary angiography does not provide clinical benefit compared with a delayed or selective invasive approach for patients 1 year after resuscitated OHCA of presumed coronary cause and without ST-segment elevation. Trial Registration: ClinicalTrials.gov Identifier: NCT02750462.
Asunto(s)
Insuficiencia Cardíaca , Infarto del Miocardio , Paro Cardíaco Extrahospitalario , Humanos , Masculino , Persona de Mediana Edad , Anciano , Femenino , Angiografía Coronaria/efectos adversos , Paro Cardíaco Extrahospitalario/diagnóstico por imagen , Paro Cardíaco Extrahospitalario/terapia , Hospitalización , Infarto del Miocardio/complicaciones , Insuficiencia Cardíaca/complicacionesRESUMEN
INTRODUCTION: Cardiogenic shock due to myocardial infarction or heart failure entails a reduction in end organ perfusion. Patients who cannot be stabilized with inotropes and who experience increasing circulatory failure are in need of an extracorporeal mechanical support system. Today, small, percutaneously implantable cardiac assist devices are available and might be a solution to reduce mortality and complications. A temporary, ventricular, continuous flow propeller pump using magnetic levitation (Impella®) has been approved for that purpose. METHODS AND STUDY DESIGN: JenaMACS (Jena Mechanical Assist Circulatory Support) is a monocenter, proof-of-concept study to determine whether treatment with an Impella CP® leads to improvement of hemodynamic parameters in patients with cardiogenic shock requiring extracorporeal, hemodynamic support. The primary outcomes of JenaMACS are changes in hemodynamic parameters measured by pulmonary artery catheterization and changes in echocardiographic parameters of left and right heart function before and after Impella® implantation at different support levels after 24 h of support. Secondary outcome measures are hemodynamic and echocardiographic changes over time as well as clinical endpoints such as mortality or time to hemodynamic stabilization. Further, laboratory and clinical safety endpoints including severe bleeding, stroke, neurological outcome, peripheral ischemic complications and occurrence of sepsis will be assessed. JenaMACS addresses essential questions of extracorporeal, mechanical, cardiac support with an Impella CP® device in patients with cardiogenic shock. Knowledge of the acute and subacute hemodynamic and echocardiographic effects may help to optimize therapy and improve the outcome in those patients. CONCLUSION: The JenaMACS study will address essential questions of extracorporeal, mechanical, cardiac support with an Impella CP® assist device in patients with cardiogenic shock. Knowledge of the acute and subacute hemodynamic and echocardiographic effects may help to optimize therapy and may improve outcome in those patients. ETHICS AND DISSEMINATION: The protocol was approved by the institutional review board and ethics committee of the University Hospital of Jena. Written informed consent will be obtained from all participants of the study. The results of this study will be published in a renowned international medical journal, irrespective of the outcomes of the study. Strengths and Limitations: JenaMACS is an innovative approach to characterize the effect of additional left ventricular mechanical unloading during cardiogenic shock via a minimally invasive cardiac assist system (Impella CP®) 24 h after onset and will provide valuable data for acute interventional strategies or future prospective trials. However, JenaMACS, due to its proof-of-concept design, is limited by its single center protocol, with a small sample size and without a comparison group.
RESUMEN
OBJECTIVES: The concept of neovascularization in response to tissue ischemia was recently extended by the finding of postnatal vasculogenesis through circulating endothelial progenitor cells (EPCs). The aim of this study was to assess the role of acute ischemia for EPC mobilization in patients with peripheral arterial occlusive disease (PAOD) and in healthy volunteers. METHODS: The number of circulating EPCs was analyzed by flow cytometry in PAOD patients (n = 23) with exercise-induced limb ischemia for up to 72 h after a maximal treadmill test and in healthy volunteers (n = 17) who underwent a 15-min suprasystolic occlusion of one lower extremity to induce limb ischemia. Plasma concentrations of vascular endothelial growth factor, basic fibroblast growth factor, tumor necrosis factor-α, and granulocyte macrophage-colony stimulating factor were determined by ELISA. RESULTS: EPCs (CD 34 pos/KDRpos) increased significantly in both PAOD patients from 82 ± 20 to 256 ± 52 (P < 0.05) and healthy volunteers from 144 ± 39 to 590 ± 61 cells per 1 million events (P < 0.05) in response to induced ischemia, with a maximum after 24 h and returned to baseline within 72 h. The relative increase in EPC numbers was significantly lower in patients with PAOD as compared with healthy volunteers (P < 0.05). Plasma levels of vascular endothelial growth factor increased from 27.4 ± 3.1 to 126.4 ± 12 pg/ml in patients with PAOD (P < 0.05) and from 30.7 ± 6.1 to 134.1 ± 12.4 pg/ml in healthy volunteers (P < 0.05). CONCLUSION: Both patients with symptomatic PAOD and healthy volunteers respond to a single episode of limb ischemia with a time-dependent increase in circulating EPCs. The increase of EPC numbers in response to ischemia is reduced when vascular disease is present, underlining the reduced vasculogenic potential of patients with PAOD.
Asunto(s)
Células Endoteliales/patología , Tolerancia al Ejercicio , Isquemia/complicaciones , Extremidad Inferior/irrigación sanguínea , Enfermedad Arterial Periférica/complicaciones , Células Madre/patología , Adulto , Biomarcadores/sangre , Estudios de Casos y Controles , Movimiento Celular , Células Cultivadas , Células Endoteliales/metabolismo , Ensayo de Inmunoadsorción Enzimática , Prueba de Esfuerzo , Femenino , Factor 2 de Crecimiento de Fibroblastos/sangre , Citometría de Flujo , Alemania , Factor Estimulante de Colonias de Granulocitos y Macrófagos/sangre , Humanos , Isquemia/sangre , Isquemia/patología , Isquemia/fisiopatología , Masculino , Persona de Mediana Edad , Neovascularización Fisiológica , Enfermedad Arterial Periférica/sangre , Enfermedad Arterial Periférica/patología , Enfermedad Arterial Periférica/fisiopatología , Estudios Prospectivos , Células Madre/metabolismo , Factores de Tiempo , Torniquetes , Factor de Necrosis Tumoral alfa/sangre , Factor A de Crecimiento Endotelial Vascular/sangreRESUMEN
AIMS: Abuse of crystal methamphetamine (MA) poses a growing problem for health services worldwide. This review summarizes the current literature on the effects of MA on the cardiovascular system. METHODS AND RESULTS: This article is a presentation of a case report and review of the current literature. In Europe, especially the eastern countries and the eastern states of Germany are affected. MA increases the concentration of catecholamines in the synaptic gap leading to euphoria, alertness, and hunger suppression as well as psychiatric and gastrointestinal complications. MA consumption is associated with hypertension, acute and chronic myocardial toxicity, stroke, coronary artery disease, and sudden cardiac death. Although many aspects of the underlying pathophysiology remain unknown, catecholamine-mediated pathologies appear to play an important role. The duration of MA consumption is the most important determinant for the prognosis. CONCLUSIONS: Awareness is needed as cardiac complications are important causes of morbidity and mortality in patients with MA consumption. Drug abstinence is the mainstay of therapy, cardiac and other complications should be treated according to the respective guidelines. Incompliance to therapy and frequent relapses are the main challenges for successful treatment. Further research is required to improve the understanding of this rapidly increasing cardiomyopathy.
Asunto(s)
Enfermedades Cardiovasculares , Metanfetamina , Enfermedades Cardiovasculares/epidemiología , Enfermedades Cardiovasculares/etiología , Europa (Continente) , Alemania , Corazón , Humanos , Metanfetamina/efectos adversosRESUMEN
Contrast-flow quantitative flow ratio (cQFR) is a new technology for quantitative evaluation of coronary stenosis using computational fluid dynamics based on angiograms. The aim of this study was to assess the sensitivity and specificity of cQFR to detect myocardial ischemia using stress magnetic resonance imaging (MRI) as a reference standard. Patients who received stress MRI and coronary angiography were selected from the hospital database. Relevant ischemia on stress MRI was defined as a perfusion deficit in ≥ 2 of 16 segments. cQFR was quantitated based on 3-dimensional quantitative coronary angiography using QAngio XA3D1.1 software by two blinded and independent investigators. A cQFR of ≤ 0.80 was considered abnormal. Among 87 patients 230 vessels met the criteria for full analysis by cQFR (88%). In vascular territories with a significant perfusion deficit, cQFR was significantly lower compared to areas with normal perfusion (0.72 (0.62-0.78) vs. 0.96 (0.89-0.99); p < 0.001). The sensitivity of cQFR in detecting significant epicardial stenoses of coronary vessels with documented ischemia in stress MRI was 81% (68-90%), the specificity was 88% (82-92%). Diameter stenoses (DS) and area stenoses (AS) in vessels with positive stress MRI were significantly higher than in vessels without ischemia (DS 59.1% (49.4-68.4%) vs. 34.8% (27.1-46.1%) p < 0.001; AS 75.6% (63.0-85.2%) vs. 45.0% (30.8-63.6%), p < 0.001). The analysis reveals a high correlation between coronary stenosis measured by cQFR and ischemic areas detected by stress MRI. The data set the stage to plan randomized studies assessing cQFR measurements with regard to clinical outcomes.
Asunto(s)
Angiografía Coronaria , Enfermedad de la Arteria Coronaria/diagnóstico por imagen , Circulación Coronaria , Estenosis Coronaria/diagnóstico por imagen , Vasos Coronarios/diagnóstico por imagen , Imagen por Resonancia Cinemagnética , Anciano , Velocidad del Flujo Sanguíneo , Enfermedad de la Arteria Coronaria/fisiopatología , Estenosis Coronaria/fisiopatología , Vasos Coronarios/fisiopatología , Bases de Datos Factuales , Femenino , Humanos , Masculino , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Interpretación de Imagen Radiográfica Asistida por Computador , Reproducibilidad de los Resultados , Estudios Retrospectivos , Función Ventricular IzquierdaRESUMEN
BACKGROUND: A novel stent platform eluting biolimus, a sirolimus analogue, from a biodegradable polymer showed promising results in preliminary studies. We compared the safety and efficacy of a biolimus-eluting stent (with biodegradable polymer) with a sirolimus-eluting stent (with durable polymer). METHODS: We undertook a multicentre, assessor-blind, non-inferiority study in ten European centres. 1707 patients aged 18 years or older with chronic stable coronary artery disease or acute coronary syndromes were centrally randomised by a computer-generated allocation sequence to treatment with either biolimus-eluting (n=857) or sirolimus-eluting (n=850) stents. The primary endpoint was a composite of cardiac death, myocardial infarction, or clinically-indicated target vessel revascularisation within 9 months. Analysis was by intention to treat. 427 patients were randomly allocated to angiographic follow-up, with in-stent percentage diameter stenosis as principal outcome measure at 9 months. The trial is registered with ClinicalTrials.gov, number NCT00389220. FINDINGS: We analysed all randomised patients. Biolimus-eluting stents were non-inferior to sirolimus-eluting stents for the primary endpoint at 9 months (79 [9%] patients vs 89 [11%], rate ratio 0.88 [95% CI 0.64-1.19], p for non-inferiority=0.003, p for superiority=0.39). Frequency of cardiac death (14 [1.6%] vs 21 [2.5%], p for superiority=0.22), myocardial infarction (49 [5.7%] vs 39 [4.6%], p=0.30), and clinically-indicated target vessel revascularisation (38 [4.4%] vs 47 [5.5%], p=0.29) were similar for both stent types. 168 (79%) patients in the biolimus-eluting group and 167 (78%) in the sirolimus-eluting group had data for angiographic follow-up available. Biolimus-eluting stents were non-inferior to sirolimus-eluting stents in in-stent percentage diameter stenosis (20.9%vs 23.3%, difference -2.2% [95% CI -6.0 to 1.6], p for non-inferiority=0.001, p for superiority=0.26). INTERPRETATION: Our results suggest that a stent eluting biolimus from a biodegradable polymer represents a safe and effective alternative to a stent eluting sirolimus from a durable polymer in patients with chronic stable coronary artery disease or acute coronary syndromes. FUNDING: Biosensors Europe SA, Switzerland.
Asunto(s)
Implantes Absorbibles , Enfermedad Coronaria/terapia , Stents Liberadores de Fármacos , Polímeros , Sirolimus/análogos & derivados , Sirolimus/administración & dosificación , Implantes Absorbibles/efectos adversos , Anciano , Materiales Biocompatibles/efectos adversos , Enfermedad Crónica , Stents Liberadores de Fármacos/efectos adversos , Femenino , Humanos , Masculino , Ensayo de Materiales , Metales , Persona de Mediana Edad , Polímeros/efectos adversos , Trombosis/etiología , Resultado del TratamientoRESUMEN
AIMS: In late-stage chronic heart failure (CHF), elevated cytokines and cachexia are often observed. Several studies have shown that exercise training exerts beneficial effects on skeletal muscle in this setting. Furthermore, it has been shown that the expression of myostatin, a key regulator of skeletal muscle mass, is increased in a variety of cachectic states. This study aimed to investigate the expression of myostatin in CHF, the influence of exercise training on myostatin levels, and regulation of myostatin by tumour necrosis factor-alpha (TNF-alpha). METHODS AND RESULTS: In an animal model of CHF (LAD-ligation model), protein expression of myostatin was elevated 2.4-fold in the skeletal muscle and more than four-times in the myocardium, compared with control (Co). Exercise training on a treadmill over 4 weeks led to a significant reduction in myostatin protein expression in the skeletal muscle and the myocardium of CHF animals, with values returning to baseline levels. In differentiated C2C12 cells, TNF-alpha induced the expression of myostatin through a p38MAPK-dependent pathway involving nuclear factor kappa-B (NF-kappaB). The increased TNF-alpha mRNA levels in the skeletal muscle of CHF animals correlated significantly with myostatin expression. CONCLUSION: These alterations in myostatin expression in the skeletal and heart muscle following exercise training could help to explain the beneficial anti-catabolic effects of exercise training in CHF.
Asunto(s)
Terapia por Ejercicio/métodos , Expresión Génica , Insuficiencia Cardíaca/rehabilitación , Músculo Esquelético/metabolismo , Miocardio/metabolismo , Miostatina/genética , ARN/genética , Animales , Células Cultivadas , Modelos Animales de Enfermedad , Electroforesis en Gel de Poliacrilamida , Insuficiencia Cardíaca/genética , Insuficiencia Cardíaca/metabolismo , Músculo Esquelético/patología , Miocardio/patología , Miostatina/biosíntesis , Ratas , Ratas Endogámicas WKY , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Factor de Necrosis Tumoral alfa/biosíntesis , Factor de Necrosis Tumoral alfa/genéticaRESUMEN
BACKGROUND: Statins and angiotensin type 1 (AT1) receptor blockers reduce cardiovascular mortality and morbidity. In the Endothelial Protection, AT1 blockade and Cholesterol-Dependent Oxidative Stress (EPAS) trial, impact of independent or combined statin and AT1 receptor blocker therapy on endothelial expression of anti-atherosclerotic and proatherosclerotic genes and endothelial function in arteries of patients with coronary artery disease were tested. METHODS AND RESULTS: Sixty patients with stable coronary artery disease undergoing elective coronary artery bypass grafting (CABG) surgery were randomized 4 weeks before surgery to: (A) control without inhibition of renin-angiotensin system or statin; (B) statin (pravastatin 40 mg/d); (C) AT1 blockade (irbesartan 150 mg/d); or (D) combination of statin and AT1 blocker in same dosages. Primary end point was a priori therapy-dependent regulation of an anti-atherosclerotic endothelial expression quotient Q including mRNA expression (in arbitrary units measured by real-time polymerase chain reaction) of endothelial nitric oxide synthase and C-type natriuretic peptide, divided by expression of oxidized low-density lipoprotein receptor LOX-1 and NAD(P)H oxidase subunit gp91phox in left internal mammary arteries biopsies obtained by CABG surgery; 49 patients completed the study. Statin therapy increased lnQ from 3.2+/-0.4 to 4.4+/-0.4 significantly versus control. AT(1) blockade showed a trend to increase lnQ to 4.2+/-0.5. Combination of statin and AT1 blocker further increased lnQ to 5.1+/-0.6, but a putative interaction of both therapies in lnQ was not significant. Furthermore, preoperative therapy with statin, AT1 blocker and their combination improved endothelial function in internal mammary artery rings. CONCLUSIONS: Statin and AT1 blocker therapy independently and in combination improve an anti-atherosclerotic endothelial expression quotient and endothelial function.
Asunto(s)
Bloqueadores del Receptor Tipo 1 de Angiotensina II/uso terapéutico , Compuestos de Bifenilo/uso terapéutico , Puente de Arteria Coronaria , Enfermedad Coronaria/cirugía , Inhibidores de Hidroximetilglutaril-CoA Reductasas/uso terapéutico , Pravastatina/uso terapéutico , Tetrazoles/uso terapéutico , Bloqueadores del Receptor Tipo 1 de Angiotensina II/administración & dosificación , Aterosclerosis/etiología , Aterosclerosis/genética , Aterosclerosis/prevención & control , Compuestos de Bifenilo/administración & dosificación , Presión Sanguínea/efectos de los fármacos , Colesterol/sangre , LDL-Colesterol/sangre , Quimioterapia Combinada , Procedimientos Quirúrgicos Electivos , Regulación de la Expresión Génica/efectos de los fármacos , Humanos , Hipercolesterolemia/complicaciones , Hipercolesterolemia/tratamiento farmacológico , Irbesartán , Arterias Mamarias/metabolismo , Glicoproteínas de Membrana/biosíntesis , Glicoproteínas de Membrana/genética , Músculo Liso Vascular/efectos de los fármacos , NADPH Oxidasa 2 , NADPH Oxidasas/biosíntesis , NADPH Oxidasas/genética , Péptido Natriurético Tipo-C/biosíntesis , Péptido Natriurético Tipo-C/genética , Óxido Nítrico Sintasa de Tipo III/biosíntesis , Óxido Nítrico Sintasa de Tipo III/genética , Estrés Oxidativo , Reacción en Cadena de la Polimerasa , Pravastatina/administración & dosificación , ARN Mensajero/biosíntesis , ARN Mensajero/genética , Receptor de Angiotensina Tipo 1/fisiología , Sistema Renina-Angiotensina/efectos de los fármacos , Sistema Renina-Angiotensina/fisiología , Receptores Depuradores de Clase E/biosíntesis , Receptores Depuradores de Clase E/genética , Tetrazoles/administración & dosificaciónRESUMEN
Transplantation of blood-derived circulating progenitor cells (CPC) has been shown to improve myocardial regeneration after myocardial infarction. It remains unclear whether CPC transplantation exerts beneficial effects also in patients with chronic myocardial ischemia. We initiated a randomized, double-blind, placebo-controlled study evaluating the impact of intracoronary infusion of CPCs on coronary vasomotion and left ventricular (LV) function in patients after recanalization of chronic coronary total occlusion (CTO). After recanalization of CTO, 26 patients (age, 63+/-2 years; LV ejection fraction, 53+/-2%) were randomly assigned to the treatment (intracoronary transplantation of CPCs) or control group. Coronary flow reserve in response to adenosine (2.4 mg/min) was measured in the target vessel at the beginning of the study and after 3 months. LV function and infarct size were assessed by MRI and metabolism by 18F deoxyglucose positron emission tomography. CPC application resulted in an increase in coronary flow reserve by 43% from 2.3+/-0.3 to 3.3+/-0.5 (P<0.05 versus beginning and control). At 3 months, the number of hibernating segments in the target region (from 2.9+/-0.6 to 2.0+/-0.6 segments, P<0.05 versus beginning and control) had declined in the treatment group, whereas no significant changes were observed in the control group. MRI revealed a reduction in infarct size by 16% and an increase in LV ejection fraction by 14% in the treatment group (from 51.7+/-3.7 to 58.9+/-3.2%; P<0.05 versus beginning and control) because of an augmented wall motion in the target region. Hence, intracoronary transplantation of CPCs after recanalization of CTO results in an improvement of macro- and microvascular function and contributes to the recruitment of hibernating myocardium.