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BACKGROUND: Antiretroviral therapy (ART) cannot cure HIV infection because of a persistent reservoir of latently infected cells. Approaches that force HIV transcription from these cells, making them susceptible to killing-termed kick and kill regimens-have been explored as a strategy towards an HIV cure. RIVER is the first randomised trial to determine the effect of ART-only versus ART plus kick and kill on markers of the HIV reservoir. METHODS: This phase 2, open-label, multicentre, randomised, controlled trial was undertaken at six clinical sites in the UK. Patients aged 18-60 years who were confirmed as HIV-positive within a maximum of the past 6 months and started ART within 1 month from confirmed diagnosis were randomly assigned by a computer generated randomisation list to receive ART-only (control) or ART plus the histone deacetylase inhibitor vorinostat (the kick) and replication-deficient viral vector T-cell inducing vaccines encoding conserved HIV sequences ChAdV63. HIVconsv-prime and MVA.HIVconsv-boost (the kill; ARTâ+âVâ+âV; intervention). The primary endpoint was total HIV DNA isolated from peripheral blood CD4+ T-cells at weeks 16 and 18 after randomisation. Analysis was by intention to treat. This trial is registered with ClinicalTrials.gov, NCT02336074. FINDINGS: Between June 14, 2015 and Jul 11, 2017, 60 men with HIV were randomly assigned to receive either an ART-only (n=30) or an ARTâ+âVâ+âV (n=30) regimen; all 60 participants completed the study, with no loss-to-follow-up. Mean total HIV DNA at weeks 16 and 18 after randomisation was 3·02 log10 copies HIV DNA per 106 CD4+ T-cells in the ART-only group versus 3·06 log10 copies HIV DNA per 106 CD4+ T-cells in ARTâ+âVâ+âV group, with no statistically significant difference between the two groups (mean difference of 0·04 log10 copies HIV DNA per 106 CD4+ T-cells [95% CI -0·03 to 0·11; p=0·26]). There were no intervention-related serious adverse events. INTERPRETATION: This kick and kill approach conferred no significant benefit compared with ART alone on measures of the HIV reservoir. Although this does not disprove the efficacy kick and kill strategy, for future trials enhancement of both kick and kill agents will be required. FUNDING: Medical Research Council (MR/L00528X/1).
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Vacunas contra el SIDA/administración & dosificación , Antirretrovirales/uso terapéutico , Reservorios de Enfermedades , Infecciones por VIH , Inhibidores de Histona Desacetilasas/administración & dosificación , Vorinostat/administración & dosificación , Adulto , ADN Viral/análisis , Infecciones por VIH/tratamiento farmacológico , Humanos , Masculino , Transcripción Genética/efectos de los fármacos , Resultado del TratamientoRESUMEN
OBJECTIVES: Aortic stenosis (AS) is characterised by a long and variable asymptomatic course. Our objective was to use cardiovascular magnetic resonance imaging (MRI) to assess progression of adverse remodeling in asymptomatic AS. METHODS: Participants from the PRIMID-AS study, a prospective, multi-centre observational study of asymptomatic patients with moderate to severe AS, who remained asymptomatic at 12 months, were invited to undergo a repeat cardiac MRI. RESULTS: Forty-three participants with moderate-severe AS (mean age 64.4 ± 14.8 years, 83.4% male, aortic valve area index 0.54 ± 0.15 cm2/m2) were included. There was small but significant increase in indexed left ventricular (LV) (90.7 ± 22.0 to 94.5 ± 23.1 ml/m2, p = 0.007) and left atrial volumes (52.9 ± 11.3 to 58.6 ± 13.6 ml/m2, p < 0.001), with a decrease in systolic (LV ejection fraction 57.9 ± 4.6 to 55.6 ± 4.1%, p = 0.001) and diastolic (longitudinal diastolic strain rate 1.06 ± 0.2 to 0.99 ± 0.2 1/s, p = 0.026) function, but no overall change in LV mass or mass/volume. Late gadolinium enhancement increased (2.02 to 4.26 g, p < 0.001) but markers of diffuse interstitial fibrosis did not change significantly (extracellular volume index 12.9 [11.4, 17.0] ml/m2 to 13.3 [11.1, 15.1] ml/m2, p = 0.689). There was also a significant increase in the levels of NT-proBNP (43.6 [13.45, 137.08] pg/ml to 53.4 [19.14, 202.20] pg/ml, p = 0.001). CONCLUSIONS: There is progression in cardiac remodeling with increasing scar burden even in asymptomatic AS. Given the lack of reversibility of LGE post-AVR and its association with long-term mortality post-AVR, this suggests the potential need for earlier intervention, before the accumulation of LGE, to improve the long-term outcomes in AS. KEY POINTS: ⢠Current guidelines recommend waiting until symptom onset before valve replacement in severe AS. ⢠MRI showed clear progression in cardiac remodeling over 12 months in asymptomatic patients with AS, with near doubling in LGE. ⢠This highlights the need for potentially earlier intervention or better risk stratification in AS.
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Estenosis de la Válvula Aórtica , Medios de Contraste , Anciano , Estenosis de la Válvula Aórtica/diagnóstico por imagen , Ecocardiografía , Femenino , Gadolinio , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Función Ventricular Izquierda , Remodelación VentricularRESUMEN
OBJECTIVES: To compare aortic size and stiffness parameters on MRI between bicuspid aortic valve (BAV) and tricuspid aortic valve (TAV) patients with aortic stenosis (AS). METHODS: MRI was performed in 174 patients with asymptomatic moderate-severe AS (mean AVAI 0.57 ± 0.14 cm2/m2) and 23 controls on 3T scanners. Valve morphology was available/analysable in 169 patients: 63 BAV (41 type-I, 22 type-II) and 106 TAV. Aortic cross-sectional areas were measured at the level of the pulmonary artery bifurcation. The ascending and descending aorta (AA, DA) distensibility, and pulse wave velocity (PWV) around the aortic arch were calculated. RESULTS: The AA and DA areas were lower in the controls, with no difference in DA distensibility or PWV, but slightly lower AA distensibility than in the patient group. With increasing age, there was a decrease in distensibility and an increase in PWV. After correcting for age, the AA maximum cross-sectional area was higher in bicuspid vs. tricuspid patients (12.97 [11.10, 15.59] vs. 10.06 [8.57, 12.04] cm2, p < 0.001), but there were no significant differences in AA distensibility (p = 0.099), DA distensibility (p = 0.498) or PWV (p = 0.235). Patients with BAV type-II valves demonstrated a significantly higher AA distensibility and lower PWV compared to type-I, despite a trend towards higher AA area. CONCLUSIONS: In patients with significant AS, BAV patients do not have increased aortic stiffness compared to those with TAV despite increased ascending aortic dimensions. Those with type-II BAV have less aortic stiffness despite greater dimensions. These results demonstrate a dissociation between aortic dilatation and stiffness and suggest that altered flow patterns may play a role. KEY POINTS: ⢠Both cellular abnormalities secondary to genetic differences and abnormal flow patterns have been implicated in the pathophysiology of aortic dilatation and increased vascular complications associated with bicuspid aortic valves (BAV). ⢠We demonstrate an increased ascending aortic size in patients with BAV and moderate to severe AS compared to TAV and controls, but no difference in aortic stiffness parameters, therefore suggesting a dissociation between dilatation and stiffness. ⢠Sub-group analysis showed greater aortic size but lower stiffness parameters in those with BAV type-II AS compared to BAV type-I.
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Estenosis de la Válvula Aórtica/diagnóstico por imagen , Estenosis de la Válvula Aórtica/fisiopatología , Válvula Aórtica/anomalías , Enfermedades de las Válvulas Cardíacas/diagnóstico por imagen , Imagen por Resonancia Magnética , Válvula Tricúspide/diagnóstico por imagen , Rigidez Vascular , Adulto , Anciano , Aorta/fisiopatología , Aorta Torácica/diagnóstico por imagen , Aorta Torácica/patología , Aorta Torácica/fisiopatología , Válvula Aórtica/diagnóstico por imagen , Válvula Aórtica/patología , Válvula Aórtica/fisiopatología , Estenosis de la Válvula Aórtica/patología , Enfermedad de la Válvula Aórtica Bicúspide , Dilatación Patológica , Femenino , Enfermedades de las Válvulas Cardíacas/patología , Enfermedades de las Válvulas Cardíacas/fisiopatología , Humanos , Masculino , Persona de Mediana Edad , Análisis de la Onda del Pulso , Válvula Tricúspide/patología , Válvula Tricúspide/fisiopatologíaRESUMEN
AIMS: To assess cardiovascular magnetic resonance (CMR) measured myocardial perfusion reserve (MPR) and exercise testing in asymptomatic patients with moderate-severe AS. METHODS AND RESULTS: Multi-centre, prospective, observational study, with blinded analysis of CMR data. Patients underwent adenosine stress CMR, symptom-limited exercise testing (ETT) and echocardiography and were followed up for 12-30 months. The primary outcome was a composite of: typical AS symptoms necessitating referral for AVR, cardiovascular death and major adverse cardiovascular events. 174 patients were recruited: mean age 66.2 ± 13.34 years, 76% male, peak velocity 3.86 ± 0.56 m/s and aortic valve area index 0.57 ± 0.14 cm2/m2. A primary outcome occurred in 47 (27%) patients over a median follow-up of 374 (IQR 351-498) days. The mean MPR in those with and without a primary outcome was 2.06 ± 0.65 and 2.34 ± 0.70 (P = 0.022), while the incidence of a symptom-limited ETT was 45.7% and 27.0% (P = 0.020), respectively. MPR showed moderate association with outcome area under curve (AUC) = 0.61 (0.52-0.71, P = 0.020), as did exercise testing (AUC = 0.59 (0.51-0.68, P = 0.027), with no significant difference between the two. CONCLUSIONS: MPR was associated with symptom-onset in initially asymptomatic patients with AS, but with moderate accuracy and was not superior to symptom-limited exercise testing. ClinicalTrials.gov (NCT01658345).
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Estenosis de la Válvula Aórtica/fisiopatología , Circulación Coronaria/fisiología , Tolerancia al Ejercicio/fisiología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Área Bajo la Curva , Prueba de Esfuerzo , Femenino , Humanos , Angiografía por Resonancia Magnética , Masculino , Persona de Mediana Edad , Pronóstico , Estudios Prospectivos , Adulto JovenRESUMEN
BACKGROUND: The CvLPRIT study showed a trend for improved clinical outcomes in the complete revascularisation (CR) group in those treated with an immediate, as opposed to staged in-hospital approach in patients with multivessel coronary disease undergoing primary percutaneous intervention (PPCI). We aimed to assess infarct size and left ventricular function in patients undergoing immediate compared with staged CR for multivessel disease at PPCI. METHODS: The Cardiovascular Magnetic Resonance (CMR) substudy of CvLPRIT was a multicentre, prospective, randomized, open label, blinded endpoint trial in PPCI patients with multivessel disease. These data refer to a post-hoc analysis in 93 patients randomized to the CR arm (63 immediate, 30 staged) who completed a pre-discharge CMR scan (median 2 and 4 days respectively) after PPCI. The decision to stage non-IRA revascularization was at the discretion of the treating interventional cardiologist. RESULTS: Patients treated with a staged approach had more visible thrombus (26/30 vs. 31/62, p = 0.001), higher SYNTAX score in the IRA (9.5, 8-16 vs. 8.0, 5.5-11, p = 0.04) and a greater incidence of no-reflow (23.3 % vs. 1.6 % p < 0.001) than those treated with immediate CR. After adjustment for confounders, staged patients had larger infarct size (19.7 % [11.7-37.6] vs. 11.6 % [6.8-18.2] of LV Mass, p = 0.012) and lower ejection fraction (42.2 ± 10 % vs. 47.4 ± 9 %, p = 0.019) compared with immediate CR. CONCLUSIONS: Of patients randomized to CR in the CMR substudy of CvLPRIT, those in whom the operator chose to stage revascularization had larger infarct size and lower ejection fraction, which persisted after adjusting for important covariates than those who underwent immediate CR. Prospective randomized trials are needed to assess whether immediate CR results in better clinical outcomes than staged CR. TRIAL REGISTRATION: ISRCTN70913605 , Registered 24th February 2011.
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Enfermedad de la Arteria Coronaria/terapia , Imagen por Resonancia Magnética , Miocardio/patología , Intervención Coronaria Percutánea/métodos , Infarto del Miocardio con Elevación del ST/terapia , Función Ventricular Izquierda , Anciano , Angiografía Coronaria , Enfermedad de la Arteria Coronaria/diagnóstico por imagen , Enfermedad de la Arteria Coronaria/patología , Enfermedad de la Arteria Coronaria/fisiopatología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Selección de Paciente , Intervención Coronaria Percutánea/efectos adversos , Valor Predictivo de las Pruebas , Estudios Prospectivos , Factores de Riesgo , Infarto del Miocardio con Elevación del ST/diagnóstico por imagen , Infarto del Miocardio con Elevación del ST/patología , Infarto del Miocardio con Elevación del ST/fisiopatología , Volumen Sistólico , Factores de Tiempo , Resultado del TratamientoRESUMEN
Mouth rinsing with carbohydrate (CHO) solutions during cycling time trials results in performance enhancements; however, most studies have used approximately 6% CHO solutions. Therefore, the purpose of this study was to compare the effectiveness of mouth rinsing with 4, 6, and 8% CHO solutions on 1-hour simulated cycling time trial performance. On 4 occasions, 7 trained male cyclists completed at the postprandial period, a set amount of work as fast as possible in a randomized counterbalanced order. The subjects rinsed their mouth for 5 seconds, on completion of each 12.5% of the trial, with 25 ml of a non-CHO placebo and 4, 6, and 8% CHO solutions. No additional fluids were consumed during the time trial. Heart rate (HR), ratings of perceived exertion (RPE), thirst (TH), and subjective feelings (SF) were recorded after each rinse. Furthermore, blood samples were drawn every 25% of the trial to measure blood glucose and blood lactate concentrations, whereas whole-body CHO oxidation was monitored continuously. Time to completion was not significant between conditions with the placebo, 4, 6, and 8% conditions completing the trials in 62.0 ± 3.0, 62.8 ± 4.0, 63.4 ± 3.4, and 63 ± 4.0 minutes, respectively. There were no significant differences between conditions in any of the variables mentioned above; however, significant time effects were observed for HR, RPE, TH, and SF. Post hoc analysis showed that TH and SF of subjects in the CHO conditions but not in the placebo were significantly increased by completion of the time trial. In conclusion, mouth rinsing with CHO solutions did not impact 1-hour cycling performance in the postprandial period and in the absence of fluid intake. Our findings suggest that there is scope for further research to explore the activation regions of the brain and whether they are receptive to CHO dose, before specific recommendations for athletic populations are established. Consequently, mouth rinsing as a practical strategy for coaches and athletes is questionable under specific conditions and should be carefully considered before its inclusion. Emphasis should be focused on appropriate dietary and fluid strategies during training and competition.
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Rendimiento Atlético/fisiología , Ciclismo/fisiología , Carbohidratos de la Dieta/administración & dosificación , Administración Oral , Adulto , Glucemia/metabolismo , Prueba de Esfuerzo , Frecuencia Cardíaca , Humanos , Ácido Láctico/sangre , Masculino , Esfuerzo Físico , Periodo Posprandial , Sed , Adulto JovenRESUMEN
OBJECTIVE: To characterise cardiac remodelling, exercise capacity and fibroinflammatory biomarkers in patients with aortic stenosis (AS) with and without diabetes, and assess the impact of diabetes on outcomes. METHODS: Patients with moderate or severe AS with and without diabetes underwent echocardiography, stress cardiovascular magnetic resonance (CMR), cardiopulmonary exercise testing and plasma biomarker analysis. Primary endpoint for survival analysis was a composite of cardiovascular mortality, myocardial infarction, hospitalisation with heart failure, syncope or arrhythmia. Secondary endpoint was all-cause death. RESULTS: Diabetes (n=56) and non-diabetes groups (n=198) were well matched for age, sex, ethnicity, blood pressure and severity of AS. The diabetes group had higher body mass index, lower estimated glomerular filtration rate and higher rates of hypertension, hyperlipidaemia and symptoms of AS. Biventricular volumes and systolic function were similar, but the diabetes group had higher extracellular volume fraction (25.9%±3.1% vs 24.8%±2.4%, p=0.020), lower myocardial perfusion reserve (2.02±0.75 vs 2.34±0.68, p=0.046) and lower percentage predicted peak oxygen consumption (68%±21% vs 77%±17%, p=0.002) compared with the non-diabetes group. Higher levels of renin (log10renin: 3.27±0.59 vs 2.82±0.69 pg/mL, p<0.001) were found in diabetes. Multivariable Cox regression analysis showed diabetes was not associated with cardiovascular outcomes, but was independently associated with all-cause mortality (HR 2.04, 95% CI 1.05 to 4.00; p=0.037). CONCLUSIONS: In patients with moderate-to-severe AS, diabetes is associated with reduced exercise capacity, increased diffuse myocardial fibrosis and microvascular dysfunction, but not cardiovascular events despite a small increase in mortality.
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Estenosis de la Válvula Aórtica , Diabetes Mellitus , Humanos , Tolerancia al Ejercicio , Renina , Estenosis de la Válvula Aórtica/diagnóstico por imagen , CorazónRESUMEN
BACKGROUND: Congestive heart failure (CHF) is a major source of morbidity, mortality, and health-care resource consumption. However, the incidence of symptomatic CHF after primary percutaneous coronary intervention (PCI) for ST-segment elevation myocardial infarction (STEMI) has rarely been fully reported. We therefore examined the early and late incidence, predictors, and implications of CHF in the large-scale, prospective, randomized HORIZONS-AMI trial. METHODS AND RESULTS: New York Heart Association (NYHA) functional classification was prospectively collected from patient-level data at baseline, 30 days, 6 months, and at 1 and 2 years from 3,343 patients with STEMI undergoing PCI at 123 centers in 11 countries. The baseline incidence of CHF (before the index STEMI) was 2.6%, increasing to 4.6% 1 month after primary PCI (P < .0001), 4.7% at 1 year, and 5.1% at 2 years. The incidence of NYHA class III/IV symptoms was 0.4% at baseline and 0.8% at 2 years (P = .03). CHF at 1 year was associated with diabetes (P < .0001), dyslipidemia (P = .009), previous MI (P < .0001), previous revascularization (P = .01), anterior STEMI (P = .02), and baseline TIMI grade 0 flow (P = .01) but not procedural anticoagulation with bivalirudin versus heparin + GPIIb/IIIa inhibitors (P = .93) or use of drug-eluting versus bare metal stents (P = .66). Among patients in whom CHF was not present at baseline but developed after PCI, the rate of all-cause mortality was significantly higher during 2-year follow-up (7.3% vs 2.0%, P < .0001), as was cardiac mortality (2.4% vs 0.8%, P = .004), reinfarction (9.4% vs 5.2%, P = .0009), stent thrombosis (7.0% vs 3.8%, P = .007), and ischemic target vessel revascularization (19.4% vs 11.8%, P < .0001). CONCLUSION: In the HORIZONS-AMI trial, the development of new-onset CHF within 2 years after contemporary PCI, although infrequent, was associated with significantly increased rates of mortality and major adverse ischemic events.
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Angioplastia Coronaria con Balón , Insuficiencia Cardíaca/epidemiología , Infarto del Miocardio/cirugía , Anciano , Femenino , Insuficiencia Cardíaca/etiología , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Infarto del Miocardio/complicaciones , Infarto del Miocardio/fisiopatología , Estudios ProspectivosRESUMEN
A 28 year-old lady with severe rheumatic mitral stenosis presented with non-ST-elevation myocardial infarction secondary to angiographically confirmed right coronary artery embolus with a likely source of mitral valve stenosis origin. This patient was successfully treated medically with dual anti-platelet and 72 hours of intravenous heparin, glycoprotein IIb/IIIa inhibitor and eptifibitide (Integrilin) with a repeated coronary angiogram showing complete resolution of embolus. The management of embolic myocardial infarction is discussed along with the risks of embolism in patients with mitral stenosis who remain in sinus rhythm.
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Anticoagulantes/administración & dosificación , Vasos Coronarios , Embolia , Heparina/administración & dosificación , Estenosis de la Válvula Mitral , Infarto del Miocardio , Péptidos/administración & dosificación , Inhibidores de Agregación Plaquetaria/administración & dosificación , Adulto , Embolia/tratamiento farmacológico , Embolia/etiología , Embolia/fisiopatología , Eptifibatida , Femenino , Humanos , Estenosis de la Válvula Mitral/complicaciones , Estenosis de la Válvula Mitral/tratamiento farmacológico , Estenosis de la Válvula Mitral/fisiopatología , Infarto del Miocardio/tratamiento farmacológico , Infarto del Miocardio/etiología , Infarto del Miocardio/fisiopatología , Complejo GPIIb-IIIa de Glicoproteína Plaquetaria/antagonistas & inhibidores , Factores de RiesgoRESUMEN
With the obvious eldercare capabilities of smart environments it is a question of "when", rather than "if", these technologies will be routinely integrated into the design of future houses. In the meantime, health monitoring applications must be integrated into already complete home environments. However, there is significant effort involved in installing the hardware necessary to monitor the movements of an elder throughout an environment. Our work seeks to address the high infrastructure requirements of traditional location-based smart home systems by developing an extremely low infrastructure localisation technique. A study of the most efficient method of obtaining calibration data for an environment is conducted and different mobile devices are compared for localisation accuracy and cost trade-off. It is believed that these developments will contribute towards more efficiently deployed location-based smart home systems.
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Servicios de Atención de Salud a Domicilio , Viviendas para Ancianos , Monitoreo Ambulatorio/métodos , Actividades Cotidianas , Anciano , Algoritmos , Inteligencia Artificial , Redes de Comunicación de Computadores , Diseño de Equipo , Humanos , Monitoreo Ambulatorio/economía , Monitoreo Ambulatorio/instrumentación , Monitoreo Ambulatorio/tendencias , Procesamiento de Señales Asistido por ComputadorRESUMEN
BACKGROUND: Randomized trials have shown that complete revascularization in patients with ST-segment elevation myocardial infarction (MI) with multivessel disease results in lower major adverse cardiovascular events (MACE) (all-cause death, MI, ischemia-driven revascularization, heart failure). OBJECTIVES: The goal of this study was to determine whether the benefits of complete revascularization are sustained long-term and their impact on hard endpoints. METHODS: CvLPRIT (Complete versus Lesion-only Primary PCI Trial) was a randomized trial of complete inpatient revascularization versus infarct-related artery revascularization only at the index admission. Randomized patients have been followed longer-term. The components of the original primary endpoint were collected from physical and electronic patient records, and from local databases for all readmissions. RESULTS: The median follow-up (achieved in >90% patients) from randomization to first event or last follow-up was 5.6 years (0.0 to 7.3 years). The primary MACE endpoint rate at this time point was 24.0% in the complete revascularization group but 37.7% of the infarct-related artery-only group (hazard ratio: 0.57; 95% confidence interval: 0.37 to 0.87; p = 0.0079). The composite endpoint of all-cause death/MI was 10.0% in the complete revascularization group versus 18.5% in the infarct-related artery-only group (hazard ratio: 0.47; 95% confidence interval: 0.25 to 0.89; p = 0.0175). In a landmark analysis (from 12 months to final follow-up), there was no significant difference between MACE, death/MI, and individual components of the primary endpoint. CONCLUSIONS: Long-term follow-up of the CvLPRIT trial shows that the significantly lower rate of MACE in the complete revascularization group, previously seen at 12 months, is sustained to a median of 5.6 years. A significant difference in composite all-cause death/MI favoring the complete revascularization was also observed. (Complete versus Lesion-only Primary PCI Trial; ISRCTN70913605).
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Intervención Coronaria Percutánea/normas , Infarto del Miocardio con Elevación del ST/terapia , Anciano , Femenino , Estudios de Seguimiento , Humanos , Análisis de Intención de Tratar , Masculino , Persona de Mediana Edad , Intervención Coronaria Percutánea/mortalidad , Reino Unido/epidemiologíaRESUMEN
OBJECTIVES: The aim of this study was to establish sex differences in remodeling and outcome in aortic stenosis (AS) and their associations with biomarkers of myocardial fibrosis. BACKGROUND: The remodeling response and timing of symptoms is highly variable in AS, and sex plays an important role. METHODS: A total of 174 patients (133 men, mean age 66.2 ± 13.3 years) with asymptomatic moderate to severe AS underwent comprehensive stress cardiac magnetic resonance imaging, transthoracic echocardiography, and biomarker analysis (matrix metalloproteinase [MMP]-2, -3, -7, -8, and -9; tissue inhibitor matrix metalloproteinases-1 and -4; syndecan-1 and -4; and N-terminal pro-B-type natriuretic peptide), and were followed up at 6-month intervals. A primary endpoint was a composite of typical AS symptoms necessitating referral for aortic valve replacement, cardiovascular death, or major adverse cardiovascular events. RESULTS: For a similar severity of AS, male patients demonstrated higher indexed left ventricular (LV) volumes and mass, more concentric remodeling (higher LV mass/volume), a trend to more late gadolinium enhancement (present in 51.1% men vs. 34.1% women; p = 0.057), and higher extracellular volume index than female patients (13.27 [interquartile range (IQR): 11.5 to 17.0] vs. 11.53 [IQR: 10.5 to 13.5] ml/m2, p = 0.017), with worse systolic and diastolic function and higher MMP-3 and syndecan-4 levels, whereas female patients had higher septal E/e'. Male sex was independently associated with indexed LV mass (ß = 13.32 [IQR: 9.59 to 17.05]; p < 0.001). During median follow-up of 374 (IQR: 351 to 498) days, a primary outcome, driven by spontaneous symptom onset, occurred in 21.8% of male and 43.9% of female patients (relative risk: 0.50 [95% confidence interval: 0.31 to 0.80]; p = 0.004). Measures of AS severity were associated with the primary outcome in both sexes, whereas N-terminal pro-B-type natriuretic peptide, MMP-3, and mass/volume were only associated in men. CONCLUSIONS: In AS, women tolerate pressure overload with less concentric remodeling and myocardial fibrosis but are more likely to develop symptoms. This may be related to higher wall stress and filling pressures in women.
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Estenosis de la Válvula Aórtica/complicaciones , Disparidades en el Estado de Salud , Hipertrofia Ventricular Izquierda/etiología , Miocardio/patología , Disfunción Ventricular Izquierda/etiología , Función Ventricular Izquierda , Remodelación Ventricular , Adaptación Fisiológica , Anciano , Estenosis de la Válvula Aórtica/diagnóstico por imagen , Estenosis de la Válvula Aórtica/patología , Estenosis de la Válvula Aórtica/fisiopatología , Biomarcadores/sangre , Progresión de la Enfermedad , Ecocardiografía , Femenino , Fibrosis , Humanos , Hipertrofia Ventricular Izquierda/diagnóstico por imagen , Hipertrofia Ventricular Izquierda/patología , Hipertrofia Ventricular Izquierda/fisiopatología , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Pronóstico , Medición de Riesgo , Factores de Riesgo , Índice de Severidad de la Enfermedad , Factores Sexuales , Factores de Tiempo , Disfunción Ventricular Izquierda/diagnóstico por imagen , Disfunción Ventricular Izquierda/patología , Disfunción Ventricular Izquierda/fisiopatologíaRESUMEN
A 73-year-old male was brought into hospital with chest pain and inferior ST elevation on ECG. The patient immediately proceeded to the catheter lab for primary percutaneous coronary intervention. Angiography did not identify any culprit lesions to account for the patient's electrocardiographic changes and ongoing symptoms of chest pain. Bedside echocardiography revealed critical aortic stenosis. Intra-aortic balloon pump (IABP) was inserted, resulting in resolution of chest pain and ST-segment changes. The patient underwent successful aortic valve (AV) replacement without the need for coronary intervention. This is a rare presentation of critical aortic stenosis (AS) presenting as ST-segment elevation myocardial infarction (STEMI). LEARNING POINTS: Aortic stenosis (AS) affects 2-9% of population above 65 years old and increases with age.AS induces ischaemia via abnormal cardiac coronary coupling.Focused clinical examination in patients with ST-segment elevation myocardial infarction (STEMI) is vital prior to cardiac catheterisation.Detection of murmurs should be followed on by an echocardiography examination.Other differentials of STEMI include acute aortopathy, endocarditis with embolus, myopericarditis and intracranial haemorrhage.
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BACKGROUND: Third-generation P2Y12 antagonists (prasugrel and ticagrelor) are recommended in guidelines on ST-segment elevation myocardial infarction. Mechanisms translating their more potent antiplatelet activity into improved clinical outcomes versus the second-generation P2Y12 antagonist clopidogrel are unclear. The aim of this post hoc analysis of the Complete Versus Lesion-Only PRImary PCI Trial-CMR (CvLPRIT-CMR) substudy was to assess whether prasugrel and ticagrelor were associated with reduced infarct size compared with clopidogrel in patients undergoing primary percutaneous coronary intervention. METHODS AND RESULTS: CvLPRIT-CMR was a multicenter, prospective, randomized, open-label, blinded end point trial in 203 ST-segment elevation myocardial infarction patients with multivessel disease undergoing primary percutaneous coronary intervention with either infarct-related artery-only or complete revascularization. P2Y12 inhibitors were administered according to local guidelines. The primary end point of infarct size on cardiovascular magnetic resonance was not significantly different between the randomized groups. P2Y12 antagonist administration was not randomized. Patients receiving clopidogrel (n=70) compared with those treated with either prasugrel or ticagrelor (n=133) were older (67.8±12 versus 61.5±10 years, P<0.001), more frequently had hypertension (49% versus 29%, P=0.007), and tended to have longer symptom-to-revascularization time (234 versus 177 minutes, P=0.05). Infarct size (median 16.1% [quartiles 1-3, 10.5-27.7%] versus 12.1% [quartiles 1-3, 4.8-20.7%] of left ventricular mass, P=0.013) and microvascular obstruction incidence (65.7% versus 48.9%, P=0.022) were significantly greater in patients receiving clopidogrel. Infarct size remained significantly different after adjustment for important covariates using both generalized linear models (P=0.048) and propensity score matching (P=0.025). CONCLUSIONS: In this analysis of CvLPRIT-CMR, third-generation P2Y12 antagonists were associated with smaller infarct size and lower microvascular obstruction incidence versus the second-generation P2Y12 antagonist clopidogrel for ST-segment elevation myocardial infarction. CLINICAL TRIAL REGISTRATION: URL: http://www.isrctn.com/ISRCTN70913605.
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Inhibidores de Agregación Plaquetaria/administración & dosificación , Antagonistas del Receptor Purinérgico P2Y/administración & dosificación , Infarto del Miocardio con Elevación del ST/tratamiento farmacológico , Adenosina/administración & dosificación , Adenosina/análogos & derivados , Anciano , Clopidogrel , Angiografía Coronaria , Estenosis Coronaria/tratamiento farmacológico , Estenosis Coronaria/patología , Esquema de Medicación , Femenino , Humanos , Angiografía por Resonancia Magnética , Masculino , Microvasos , Persona de Mediana Edad , Revascularización Miocárdica , Tamaño de los Órganos , Intervención Coronaria Percutánea , Clorhidrato de Prasugrel/administración & dosificación , Estudios Prospectivos , Infarto del Miocardio con Elevación del ST/patología , Ticagrelor , Ticlopidina/administración & dosificación , Ticlopidina/análogos & derivados , Factores de Tiempo , Resultado del TratamientoRESUMEN
BACKGROUND: Complete revascularization may improve outcomes compared with an infarct-related artery (IRA)-only strategy in patients being treated with primary percutaneous coronary intervention (PPCI) who have multivessel disease presenting with ST-segment elevation myocardial infarction (STEMI). However, there is concern that non-IRA PCI may cause additional non-IRA myocardial infarction (MI). OBJECTIVES: This study sought to determine whether in-hospital complete revascularization was associated with increased total infarct size compared with an IRA-only strategy. METHODS: This multicenter prospective, randomized, open-label, blinded endpoint clinical trial evaluated STEMI patients with multivessel disease having PPCI within 12 h of symptom onset. Patients were randomized to either IRA-only PCI or complete in-hospital revascularization. Contrast-enhanced cardiovascular magnetic resonance (CMR) was performed following PPCI (median day 3) and stress CMR at 9 months. The pre-specified primary endpoint was infarct size on pre-discharge CMR. The study had 80% power to detect a 4% difference in infarct size with 100 patients per group. RESULTS: Of the 296 patients in the main trial, 205 participated in the CMR substudy, and 203 patients (98 complete revascularization and 105 IRA-only) completed the pre-discharge CMR. The groups were well-matched. Total infarct size (median, interquartile range) was similar to IRA-only revascularization: 13.5% (6.2% to 21.9%) versus complete revascularization, 12.6% (7.2% to 22.6%) of left ventricular mass, p = 0.57 (95% confidence interval for difference in geometric means 0.82 to 1.41). The complete revascularization group had an increase in non-IRA MI on the pre-discharge CMR (22 of 98 vs. 11 of 105, p = 0.02). There was no difference in total infarct size or ischemic burden between treatment groups at follow-up CMR. CONCLUSIONS: Multivessel PCI in the setting of STEMI leads to a small increase in CMR-detected non-IRA MI, but total infarct size was not significantly different from an IRA-only revascularization strategy. (Complete Versus Lesion-Only Primary PCI Pilot Study [CvLPRIT]; ISRCTN70913605).
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Electrocardiografía , Imagen por Resonancia Cinemagnética/métodos , Infarto del Miocardio/cirugía , Miocardio/patología , Intervención Coronaria Percutánea/métodos , Angiografía Coronaria , Femenino , Humanos , Masculino , Persona de Mediana Edad , Infarto del Miocardio/diagnóstico , Proyectos Piloto , Estudios Prospectivos , Resultado del TratamientoRESUMEN
BACKGROUND: Percutaneous coronary intervention (PCI) is increasingly being performed at centers with offsite surgical support. Strong guideline endorsement of this practice has been lacking, in part because outcome data are limited to modest-size populations with short-term follow-up. OBJECTIVES: The aim of this study was to compare the outcomes of PCI performed at centers with and without surgical support in the United Kingdom between 2006 and 2012. METHODS: A retrospective analysis was performed of centrally tracked outcomes from index PCI procedures entered in the British Cardiovascular Intervention Society database between 2006 and 2012, stratified according to whether procedures were performed at centers with onsite or offsite surgical support. The primary endpoint was 30-day all-cause mortality, with secondary endpoints of mortality at 1 and 5 years. RESULTS: Outcomes at a median of 3.4 years follow-up were available for 384,013 patients, of whom 31% (n = 119,096) were treated at offsite surgical centers. In an unadjusted analysis, crude mortality rates were lower in patients treated at centers with offsite versus onsite surgical coverage (2.0% vs. 2.2%; p < 0.001). On multivariate adjustment, there were no between-group differences in survival between the naive and imputed populations at 30 days (naive population hazard ratio [HR]: 0.87; 95% confidence interval [CI]: 0.71 to 1.06; p = 0.16; imputed population HR: 0.99; 95% CI: 0.89 to 1.09; p = 0.82), 1 year (naive population HR: 0.92; 95% CI: 0.79 to 1.07; p = 0.26; imputed population HR: 0.99; 95% CI: 0.92 to 1.06; p = 0.78), or 5 years (naive population HR: 0.92; 95% CI: 0.84 to 1.01; p = 0.10; imputed population HR: 0.97; 95% CI: 0.92 to 1.03; p = 0.29). Results were consistent irrespective of procedural indication. No differences in mortality were seen in sensitivity analyses performed using a propensity-matched population of 74,001 patients. CONCLUSIONS: PCI performed at centers without onsite surgical backup is not associated with any mortality hazard.
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Angina Estable/cirugía , Infarto del Miocardio/cirugía , Intervención Coronaria Percutánea , Centros Quirúrgicos , Anciano , Anciano de 80 o más Años , Angina Estable/diagnóstico , Angina Estable/mortalidad , Bases de Datos Factuales , Femenino , Humanos , Masculino , Persona de Mediana Edad , Infarto del Miocardio/diagnóstico , Infarto del Miocardio/mortalidad , Estudios Retrospectivos , Tasa de Supervivencia , Resultado del Tratamiento , Reino Unido/epidemiologíaRESUMEN
BACKGROUND: The optimal management of patients found to have multivessel disease while undergoing primary percutaneous coronary intervention (P-PCI) for ST-segment elevation myocardial infarction is uncertain. OBJECTIVES: CvLPRIT (Complete versus Lesion-only Primary PCI trial) is a U.K. open-label randomized study comparing complete revascularization at index admission with treatment of the infarct-related artery (IRA) only. METHODS: After they provided verbal assent and underwent coronary angiography, 296 patients in 7 U.K. centers were randomized through an interactive voice-response program to either in-hospital complete revascularization (n = 150) or IRA-only revascularization (n = 146). Complete revascularization was performed either at the time of P-PCI or before hospital discharge. Randomization was stratified by infarct location (anterior/nonanterior) and symptom onset (≤ 3 h or >3 h). The primary endpoint was a composite of all-cause death, recurrent myocardial infarction (MI), heart failure, and ischemia-driven revascularization within 12 months. RESULTS: Patient groups were well matched for baseline clinical characteristics. The primary endpoint occurred in 10.0% of the complete revascularization group versus 21.2% in the IRA-only revascularization group (hazard ratio: 0.45; 95% confidence interval: 0.24 to 0.84; p = 0.009). A trend toward benefit was seen early after complete revascularization (p = 0.055 at 30 days). Although there was no significant reduction in death or MI, a nonsignificant reduction in all primary endpoint components was seen. There was no reduction in ischemic burden on myocardial perfusion scintigraphy or in the safety endpoints of major bleeding, contrast-induced nephropathy, or stroke between the groups. CONCLUSIONS: In patients presenting for P-PCI with multivessel disease, index admission complete revascularization significantly lowered the rate of the composite primary endpoint at 12 months compared with treating only the IRA. In such patients, inpatient total revascularization may be considered, but larger clinical trials are required to confirm this result and specifically address whether this strategy is associated with improved survival.
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Infarto del Miocardio/terapia , Intervención Coronaria Percutánea/métodos , Anciano , Angiografía Coronaria , Femenino , Insuficiencia Cardíaca/epidemiología , Humanos , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Infarto del Miocardio/diagnóstico por imagen , Infarto del Miocardio/epidemiología , Infarto del Miocardio/mortalidad , Revascularización Miocárdica/métodosRESUMEN
INTRODUCTION: Most existing conventional capacity building and educational programs are currently executed on ad-hoc basis. Such approach no longer responds to the needs and capabilities of patients, supporters and healthcare providers in their engagement with and contribution to response to HIV/AIDS. In contrast, long-term, course-like trainings have considerably broader thematic scope and are conducive to more effective and sustainable learning, exchange of experience and best practices. METHOD: Over the period of one year, the Academy trains a cohort of 20 activists (10 from East Europe and Central Asia and 10 from Western and Southern Europe). The Academy goes beyond "treatment only" paradigm. Conceptually, five training modules are grouped under three larger domains: treatment literacy, treatment advocacy and treatment activism, thus covering most of the topics pertinent to the current discourse of HIV and related co-infections. To ensure cascade effect and sustainability of the learning, the trainees are offered participation in pan-European HIV conferences (EACS and HIV Glasgow) and resources for follow-up activities. RESULTS: The trainees empirically applied the knowledge to the benefits of their communities. In Uzbekistan, a trainee introduced EACS treatment guidelines to fellow medical students and junior doctors. In Armenia and Albania a series of small-scale trainings were held, outreaching to young homeless people who were traditionally excluded from HIV treatment and prevention discourse in the two countries. A trainee from Spain used the materials of the Academy in his work in Mozambique and the Spanish Ministry of Health. Five trainees engaged in a joint European cross-countries project on treatment literacy for young people who are most at risk of infection. CONCLUSIONS: EATG Training Academy is a unique initiative in the WHO Europe region that both trains future treatment activists and addresses treatment literacy, advocacy and advocacy topics. This type of capacity building can respond to existing HIV-related problems more effectively using less limited resources and reaching out to larger communities.
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AIMS: Primary percutaneous coronary intervention (PPCI) is the preferred strategy for acute ST-segment elevation myocardial infarction (STEMI), with evidence of improved clinical outcomes compared to fibrinolytic therapy. However, there is no consensus on how best to manage multivessel coronary disease detected at the time of PPCI, with little robust data on best management of angiographically significant stenoses detected in non-infarct-related (N-IRA) coronary arteries. CVLPRIT will determine the optimal management of N-IRA lesions detected during PPCI. METHODS AND RESULTS: CVLPRIT (Complete Versus culprit-Lesion only PRimary PCI Trial) is an open-label, prospective, randomised, multicentre trial. STEMI patients undergo verbal "assent" on presentation. Patients are included when angiographic MVD has been detected, and randomised to culprit (IRA)-only PCI (n=150) or in-patient complete multivessel PCI (n=150). Cumulative major adverse cardiac events (MACE) - all-cause mortality, recurrent MI, heart failure, need for revascularisation (PCI or CABG) will be recorded at 12 months. Secondary endpoints include safety endpoints of confirmed ischaemic stroke, intracranial haemorrhage, major non-intracranial bleeding, and repair of vascular complications. A cardiac magnetic resonance (CMR) substudy will provide mechanistic data on infarct size, myocardial salvage index and microvascular obstruction. A cost efficacy analysis will be undertaken. CONCLUSIONS: The management of multivessel coronary artery disease in the setting of PPCI for STEMI, including the timing of when to perform non-culprit-artery revascularisation if undertaken, remains unresolved. CVLPRIT will yield mechanistic insights into the myocardial consequence of N-IRA intervention undertaken during the peri-infarct period.
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Enfermedad de la Arteria Coronaria/terapia , Intervención Coronaria Percutánea , Proyectos de Investigación , Determinación de Punto Final , Humanos , Estudios ProspectivosRESUMEN
Recognition of clinical and electrocardiographic features suggestive of significant left main coronary artery disease is important, particularly in patients presenting with an acute coronary syndrome. These include hemodynamic instability and widespread ST segment depression, which are well known. In addition, ST segment elevation in lead aVr, a less recognised finding associated with severe left main disease, may be present.