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PURPOSE OF REVIEW: This review summarises the shifting paradigms in the treatment of ischemic left ventricular dysfunction, spotlighting the revascularization for ischemic ventricular dysfunction-British cardiovascular intervention society-2 (REVIVED-BCIS2) trial results and its impact on key therapeutic goals: survival, left ventricular function, arrhythmia prevention, quality of life and viability testing. RECENT FINDINGS: The REVIVED-BCIS2 trial, and its subsequent sub studies highlighted that (PCI) does not provide additional benefits to optimal medical therapy in terms of improving survival, left ventricular (LV) function, arrhythmic risk or quality of life. Additionally, viability testing did not differentiate patients who could benefit from PCI, although scar burden was found to be a significant predictor of outcome in these patients. SUMMARY: The outcomes of REVIVED have challenged multiple existing beliefs in the field of ischaemic left ventricular dysfunction management, emphasising the importance of investigating evidence free areas in our practice. Future work, including the STICH3 international consortium of trials, aims to answer some of the remaining unanswered questions.
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Disfunción Ventricular Izquierda , Humanos , Intervención Coronaria Percutánea/métodos , Isquemia Miocárdica , Calidad de VidaRESUMEN
BACKGROUND: Complete revascularization of coronary artery disease has been linked to improved outcomes in patients with preserved left ventricular (LV) function. OBJECTIVES: This study sought to identify the impact of complete revascularization in patients with severe LV dysfunction. METHODS: Patients enrolled in the REVIVED-BCIS2 (Revascularization for Ischemic Ventricular Dysfunction) trial were eligible if baseline/procedural angiograms and viability studies were available for analysis by independent core laboratories. Anatomical and viability-guided completeness of revascularization were measured by the coronary and myocardial revascularization indices (RIcoro and RImyo), respectively, where RIcoro = (change in British Cardiovascular Intervention Society Jeopardy score [BCIS-JS]) / (baseline BCIS-JS) and RImyo= (number of revascularized viable segments) / (number of viable segments supplied by diseased vessels). The percutaneous coronary intervention (PCI) group was classified as having complete or incomplete revascularization by median RIcoro and RImyo. The primary outcome was death or hospitalization for heart failure. RESULTS: Of 700 randomized patients, 670 were included. The baseline BCIS-JS and SYNTAX (Synergy Between PCI With Taxus and Cardiac Surgery) scores were 8 (Q1-Q3: 6-10) and 22 (Q1-Q3: 15-29), respectively. In those patients assigned to PCI, median RIcoro and RImyo values were 67% and 85%, respectively. Compared with the group assigned to optimal medical therapy alone, there was no difference in the likelihood of the primary outcome in those patients receiving complete anatomical or viability-guided revascularization (HR: 0.90; 95% CI: 0.62-1.32; and HR: 0.95; 95% CI: 0.66-1.35, respectively). A sensitivity analysis by residual SYNTAX score showed no association with outcome. CONCLUSIONS: In patients with severe LV dysfunction, neither complete anatomical nor viability-guided revascularization was associated with improved event-free survival compared with incomplete revascularization or treatment with medical therapy alone. (Revascularization for Ischemic Ventricular Dysfunction) [REVIVED-BCIS2]; NCT01920048).
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Isquemia Miocárdica , Revascularización Miocárdica , Humanos , Masculino , Femenino , Anciano , Persona de Mediana Edad , Isquemia Miocárdica/cirugía , Isquemia Miocárdica/fisiopatología , Revascularización Miocárdica/métodos , Intervención Coronaria Percutánea/métodos , Resultado del Tratamiento , Angiografía Coronaria , Cardiomiopatías/cirugía , Cardiomiopatías/fisiopatología , Disfunción Ventricular Izquierda/fisiopatologíaRESUMEN
BACKGROUND: Exercise electrocardiographic stress testing (EST) has historically been validated against the demonstration of obstructive coronary artery disease. However, myocardial ischemia can occur because of coronary microvascular dysfunction (CMD) in the absence of obstructive coronary artery disease. OBJECTIVES: The aim of this study was to assess the specificity of EST to detect an ischemic substrate against the reference standard of coronary endothelium-independent and endothelium-dependent microvascular function in patients with angina with nonobstructive coronary arteries (ANOCA). METHODS: Patients with ANOCA underwent invasive coronary physiological assessment using adenosine and acetylcholine. CMD was defined as impaired endothelium-independent and/or endothelium-dependent function. EST was performed using a standard Bruce treadmill protocol, with ischemia defined as the appearance of ≥0.1-mV ST-segment depression 80 ms from the J-point on electrocardiography. The study was powered to detect specificity of ≥91%. RESULTS: A total of 102 patients were enrolled (65% women, mean age 60 ± 8 years). Thirty-two patients developed ischemia (ischemic group) during EST, whereas 70 patients did not (nonischemic group); both groups were phenotypically similar. Ischemia during EST was 100% specific for CMD. Acetylcholine flow reserve was the strongest predictor of ischemia during exercise. Using endothelium-independent and endothelium-dependent microvascular dysfunction as the reference standard, the false positive rate of EST dropped to 0%. CONCLUSIONS: In patients with ANOCA, ischemia on EST was highly specific of an underlying ischemic substrate. These findings challenge the traditional belief that EST has a high false positive rate.
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Enfermedad de la Arteria Coronaria , Isquemia Miocárdica , Enfermedades Vasculares , Humanos , Femenino , Persona de Mediana Edad , Anciano , Masculino , Prueba de Esfuerzo , Enfermedad de la Arteria Coronaria/diagnóstico , Acetilcolina , Electrocardiografía , Isquemia Miocárdica/diagnóstico , IsquemiaRESUMEN
Newtown Creek is a tributary of the Hudson River Estuary. It has a legacy of both industrial pollution and sewage pollution and has been designated a Superfund site. To ameliorate the chronically low levels of dissolved oxygen detected in the Creek, the New York City Department of Environmental Protection has been installing aerators. The abundance of various bacteria in the aerosols, foams, and water, at two sites in the Creek, was studied before, during, and after the aeration process. Additionally, aerosols and dispersed foams created by the aeration process were sampled and cultured to determine what unique taxa of bacteria could be grown and identified. Taxa including Actinobacteria and Firmicutes were prevalent in cultures taken from aerosols, whereas Gammaproteobacteria were prevalent in cultures taken from foam. Campylobacteria was found to have a significant presence in both samples taken after the aerators were turned off. These taxa include potentially pathogenic bacteria and are therefore of particular concern.
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Contaminación Ambiental , Aguas del Alcantarillado , Oxígeno , Bacterias/genética , Aerosoles , Ríos/microbiologíaRESUMEN
BACKGROUND: Percutaneous coronary intervention (PCI) is frequently undertaken in patients with ischemic left ventricular systolic dysfunction. The REVIVED (Revascularization for Ischemic Ventricular Dysfunction)-BCIS2 (British Cardiovascular Society-2) trial concluded that PCI did not reduce the incidence of all-cause death or heart failure hospitalization; however, patients assigned to PCI reported better initial health-related quality of life than those assigned to optimal medical therapy (OMT) alone. The aim of this study was to assess the cost-effectiveness of PCI+OMT compared with OMT alone. METHODS: REVIVED-BCIS2 was a prospective, multicenter UK trial, which randomized patients with severe ischemic left ventricular systolic dysfunction to either PCI+OMT or OMT alone. Health care resource use (including planned and unplanned revascularizations, medication, device implantation, and heart failure hospitalizations) and health outcomes data (EuroQol 5-dimension 5-level questionnaire) on each patient were collected at baseline and up to 8 years post-randomization. Resource use was costed using publicly available national unit costs. Within the trial, mean total costs and quality-adjusted life-years (QALYs) were estimated from the perspective of the UK health system. Cost-effectiveness was evaluated using estimated mean costs and QALYs in both groups. Regression analysis was used to adjust for clinically relevant predictors. RESULTS: Between 2013 and 2020, 700 patients were recruited (mean age: PCI+OMT=70 years, OMT=68 years; male (%): PCI+OMT=87, OMT=88); median follow-up was 3.4 years. Over all follow-ups, patients undergoing PCI yielded similar health benefits at higher costs compared with OMT alone (PCI+OMT: 4.14 QALYs, £22â 352; OMT alone: 4.16 QALYs, £15â 569; difference: -0.015, £6782). For both groups, most health resource consumption occurred in the first 2 years post-randomization. Probabilistic results showed that the probability of PCI being cost-effective was 0. CONCLUSIONS: A minimal difference in total QALYs was identified between arms, and PCI+OMT was not cost-effective compared with OMT, given its additional cost. A strategy of routine PCI to treat ischemic left ventricular systolic dysfunction does not seem to be a justifiable use of health care resources in the United Kingdom. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT01920048.
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Enfermedad de la Arteria Coronaria , Insuficiencia Cardíaca , Intervención Coronaria Percutánea , Disfunción Ventricular Izquierda , Anciano , Humanos , Masculino , Enfermedad de la Arteria Coronaria/terapia , Análisis de Costo-Efectividad , Insuficiencia Cardíaca/diagnóstico , Insuficiencia Cardíaca/terapia , Estudios Prospectivos , Calidad de Vida , Resultado del Tratamiento , Disfunción Ventricular Izquierda/diagnóstico , Disfunción Ventricular Izquierda/terapia , FemeninoRESUMEN
BACKGROUND: Myocardial bridges (MBs) are prevalent and can be associated with acute and chronic ischemic syndromes. We sought to determine the substrates for ischemia in patients with angina with nonobstructive coronary arteries and a MB in the left anterior descending artery. METHODS: Patients with angina with nonobstructive coronary arteries underwent the acquisition of intracoronary pressure and flow during rest, supine bicycle exercise, and adenosine infusion. Coronary wave intensity analysis was performed, with perfusion efficiency defined as accelerating wave energy/total wave energy (%). Epicardial endothelial dysfunction was defined as a reduction in epicardial vessel diameter ≥20% in response to intracoronary acetylcholine infusion. Patients with angina with nonobstructive coronary arteries and a MB were compared with 2 angina with nonobstructive coronary arteries groups with no MB: 1 with coronary microvascular disease (CMD: coronary flow reserve, <2.5) and 1 with normal coronary flow reserve (reference: coronary flow reserve, ≥2.5). RESULTS: Ninety-two patients were enrolled in the study (30 MB, 33 CMD, and 29 reference). Fractional flow reserve in these 3 groups was 0.86±0.05, 0.92±0.04, and 0.94±0.05; coronary flow reserve was 2.5±0.5, 2.0±0.3, and 3.2±0.6. Perfusion efficiency increased numerically during exercise in the reference group (65±9%-69±13%; P=0.063) but decreased in the CMD (68±10%-50±10%; P<0.001) and MB (66±9%-55±9%; P<0.001) groups. The reduction in perfusion efficiency had distinct causes: in CMD, this was driven by microcirculation-derived energy in early diastole, whereas in MB, this was driven by diminished accelerating wave energy, due to the upstream bridge, in early systole. Epicardial endothelial dysfunction was more common in the MB group (54% versus 29% reference and 38% CMD). Overall, 93% of patients with a MB had an identifiable ischemic substrate. CONCLUSIONS: MBs led to impaired coronary perfusion efficiency during exercise, which was due to diminished accelerating wave energy in early systole compared with the reference group. Additionally, there was a high prevalence of endothelial and microvascular dysfunction. These ischemic mechanisms may represent distinct treatment targets.
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Enfermedad de la Arteria Coronaria , Reserva del Flujo Fraccional Miocárdico , Angina Microvascular , Isquemia Miocárdica , Humanos , Circulación Coronaria , Resultado del Tratamiento , Vasos Coronarios/diagnóstico por imagen , Isquemia , Microcirculación , Angiografía Coronaria , Enfermedad de la Arteria Coronaria/diagnóstico por imagen , Isquemia Miocárdica/diagnósticoRESUMEN
Quantitative and selective labelling of proteins is widely used in both academic and industrial laboratories, and catalytic labelling of proteins using transpeptidases, such as sortases, has proved to be a popular strategy for such selective modification. A major challenge for this class of enzymes is that the majority of procedures require an excess of the labelling reagent or, alternatively, activated substrates rather than simple commercially sourced peptides. We report the use of a coupled enzyme strategy which enables quantitative N- and C-terminal labelling of proteins using unactivated labelling peptides. The use of an aminopeptidase in conjunction with a transpeptidase allows sequence-specific degradation of the peptide by-product, shifting the equilibrium to favor product formation, which greatly enhances the reaction efficiency. Subsequent optimisation of the reaction allows N-terminal labelling of proteins using essentially equimolar ratios of peptide label to protein and C-terminal labelling with only a small excess. Minimizing the amount of substrate required for quantitative labelling has the potential to improve industrial processes and facilitate the use of transpeptidation as a method for protein labelling.
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Aminoaciltransferasas , Peptidil Transferasas , Aminopeptidasas , Proteínas Bacterianas/metabolismo , Aminoaciltransferasas/metabolismo , Péptidos/metabolismoRESUMEN
Importance: In the Revascularization for Ischemic Ventricular Dysfunction (REVIVED-BCIS2) trial, percutaneous coronary intervention (PCI) did not improve outcomes for patients with ischemic left ventricular dysfunction. Whether myocardial viability testing had prognostic utility for these patients or identified a subpopulation who may benefit from PCI remained unclear. Objective: To determine the effect of the extent of viable and nonviable myocardium on the effectiveness of PCI, prognosis, and improvement in left ventricular function. Design, Setting, and Participants: Prospective open-label randomized clinical trial recruiting between August 28, 2013, and March 19, 2020, with a median follow-up of 3.4 years (IQR, 2.3-5.0 years). A total of 40 secondary and tertiary care centers in the United Kingdom were included. Of 700 randomly assigned patients, 610 with left ventricular ejection fraction less than or equal to 35%, extensive coronary artery disease, and evidence of viability in at least 4 myocardial segments that were dysfunctional at rest and who underwent blinded core laboratory viability characterization were included. Data analysis was conducted from March 31, 2022, to May 1, 2023. Intervention: Percutaneous coronary intervention in addition to optimal medical therapy. Main Outcomes and Measures: Blinded core laboratory analysis was performed of cardiac magnetic resonance imaging scans and dobutamine stress echocardiograms to quantify the extent of viable and nonviable myocardium, expressed as an absolute percentage of left ventricular mass. The primary outcome of this subgroup analysis was the composite of all-cause death or hospitalization for heart failure. Secondary outcomes were all-cause death, cardiovascular death, hospitalization for heart failure, and improved left ventricular function at 6 months. Results: The mean (SD) age of the participants was 69.3 (9.0) years. In the PCI group, 258 (87%) were male, and in the optimal medical therapy group, 277 (88%) were male. The primary outcome occurred in 107 of 295 participants assigned to PCI and 114 of 315 participants assigned to optimal medical therapy alone. There was no interaction between the extent of viable or nonviable myocardium and the effect of PCI on the primary or any secondary outcome. Across the study population, the extent of viable myocardium was not associated with the primary outcome (hazard ratio per 10% increase, 0.98; 95% CI, 0.93-1.04) or any secondary outcome. The extent of nonviable myocardium was associated with the primary outcome (hazard ratio, 1.07; 95% CI, 1.00-1.15), all-cause death, cardiovascular death, and improvement in left ventricular function. Conclusions and Relevance: This study found that viability testing does not identify patients with ischemic cardiomyopathy who benefit from PCI. The extent of nonviable myocardium, but not the extent of viable myocardium, is associated with event-free survival and likelihood of improvement of left ventricular function. Trial Registration: ClinicalTrials.gov Identifier: NCT01920048.
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Insuficiencia Cardíaca , Intervención Coronaria Percutánea , Disfunción Ventricular Izquierda , Humanos , Masculino , Anciano , Femenino , Volumen Sistólico , Estudios Prospectivos , Intervención Coronaria Percutánea/efectos adversos , Estudios de Seguimiento , Función Ventricular Izquierda , Insuficiencia Cardíaca/terapia , Insuficiencia Cardíaca/complicaciones , Disfunción Ventricular Izquierda/complicacionesRESUMEN
BACKGROUND: Ventricular arrhythmia is an important cause of mortality in patients with ischemic left ventricular dysfunction. Revascularization with coronary artery bypass graft or percutaneous coronary intervention is often recommended for these patients before implantation of a cardiac defibrillator because it is assumed that this may reduce the incidence of fatal and potentially fatal ventricular arrhythmias, although this premise has not been evaluated in a randomized trial to date. METHODS: Patients with severe left ventricular dysfunction, extensive coronary disease, and viable myocardium were randomly assigned to receive either percutaneous coronary intervention (PCI) plus optimal medical and device therapy (OMT) or OMT alone. The composite primary outcome was all-cause death or aborted sudden death (defined as an appropriate implantable cardioverter defibrillator therapy or a resuscitated cardiac arrest) at a minimum of 24 months, analyzed as time to first event on an intention-to-treat basis. Secondary outcomes included cardiovascular death or aborted sudden death, appropriate implantable cardioverter defibrillator (ICD) therapy or sustained ventricular arrhythmia, and number of appropriate ICD therapies. RESULTS: Between August 28, 2013, and March 19, 2020, 700 patients were enrolled across 40 centers in the United Kingdom. A total of 347 patients were assigned to the PCI+OMT group and 353 to the OMT alone group. The mean age of participants was 69 years; 88% were male; 56% had hypertension; 41% had diabetes; and 53% had a clinical history of myocardial infarction. The median left ventricular ejection fraction was 28%; 53.1% had an implantable defibrillator inserted before randomization or during follow-up. All-cause death or aborted sudden death occurred in 144 patients (41.6%) in the PCI group and 142 patients (40.2%) in the OMT group (hazard ratio, 1.03 [95% CI, 0.82-1.30]; P=0.80). There was no between-group difference in the occurrence of any of the secondary outcomes. CONCLUSIONS: PCI was not associated with a reduction in all-cause mortality or aborted sudden death. In patients with ischemic cardiomyopathy, PCI is not beneficial solely for the purpose of reducing potentially fatal ventricular arrhythmias. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT01920048.
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Desfibriladores Implantables , Disfunción Ventricular Izquierda , Humanos , Masculino , Anciano , Femenino , Volumen Sistólico , Muerte Súbita Cardíaca/epidemiología , Muerte Súbita Cardíaca/etiología , Muerte Súbita Cardíaca/prevención & control , Función Ventricular Izquierda , Arritmias Cardíacas/etiología , Disfunción Ventricular Izquierda/etiología , Desfibriladores Implantables/efectos adversos , Resultado del TratamientoRESUMEN
Ocean acidification can severely affect bivalve molluscs, especially their shell calcification. Assessing the fate of this vulnerable group in a rapidly acidifying ocean is therefore a pressing challenge. Volcanic CO2 seeps are natural analogues of future ocean conditions that offer unique insights into the scope of marine bivalves to cope with acidification. Here, we used a 2-month reciprocal transplantation of the coastal mussel Septifer bilocularis collected from reference and elevated pCO2 habitats to explore how they calcify and grow at CO2 seeps on the Pacific coast of Japan. We found significant decreases in condition index (an indication of tissue energy reserves) and shell growth of mussels living under elevated pCO2 conditions. These negative responses in their physiological performance under acidified conditions were closely associated with changes in their food sources (shown by changes to the soft tissue δ13C and δ15N ratios) and changes in their calcifying fluid carbonate chemistry (based on shell carbonate isotopic and elemental signatures). The reduced shell growth rate during the transplantation experiment was further supported by shell δ13C records along their incremental growth layers, as well as their smaller shell size despite being of comparable ontogenetic ages (5-7 years old, based on shell δ18O records). Taken together, these findings demonstrate how ocean acidification at CO2 seeps affects mussel growth and reveal that lowered shell growth helps them survive stressful conditions.
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Mytilidae , Agua de Mar , Animales , Dióxido de Carbono , Concentración de Iones de Hidrógeno , Acidificación de los Océanos , Carbonatos , Océanos y MaresRESUMEN
Scrub typhus is a zoonosis caused by 3 species of Orientia bacteria, including Candidatus Orientia chuto. This species is known only from a human case in Dubai and infections in wildlife in Kenya. We report molecular detection of Candidatus O. chuto in 2 wild rodent species from Saudi Arabia.
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Orientia tsutsugamushi , Tifus por Ácaros , Trombiculidae , Animales , Humanos , Animales Salvajes , Orientia tsutsugamushi/genética , Arabia Saudita/epidemiología , Trombiculidae/microbiología , Tifus por Ácaros/diagnóstico , Tifus por Ácaros/epidemiología , Tifus por Ácaros/veterinaria , RoedoresRESUMEN
In the setting of non-cardiac surgery, cardiac complications contribute to over a third of perioperative deaths. With over 230 million major surgeries performed annually, and an increasing prevalence of cardiovascular risk factors and ischaemic heart disease, the incidence of perioperative myocardial infarction is also rising. The recent European Society of Cardiology guidelines on cardiovascular risk in noncardiac surgery elevated practices aiming to identify those at most risk, including biomarker monitoring and stress testing. However the current evidence base on if, and how, the risk of cardiac events can be modified is lacking. This review focuses on patient, surgical and cardiac risk assessment, as well as exploring the data on perioperative revascularization and other risk-reduction strategies.
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BACKGROUND: Coronary angiography and viability testing are the cornerstones of diagnosing and managing ischemic cardiomyopathy. At present, no single test serves both needs. Coronary wave intensity analysis interrogates both contractility and microvascular physiology of the subtended myocardium and therefore has the potential to fulfil the goal of completely assessing coronary physiology and myocardial viability in a single procedure. We hypothesized that coronary wave intensity analysis measured during coronary angiography would predict viability with a similar accuracy to late-gadolinium-enhanced cardiac magnetic resonance imaging. METHODS: Patients with a left ventricular ejection fraction ≤40% and extensive coronary disease were enrolled. Coronary wave intensity analysis was assessed during cardiac catheterization at rest, during adenosine-induced hyperemia, and during low-dose dobutamine stress using a dual pressure-Doppler sensing coronary guidewire. Scar burden was assessed with cardiac magnetic resonance imaging. Regional left ventricular function was assessed at baseline and 6-month follow-up after optimization of medical-therapy±revascularization, using transthoracic echocardiography. The primary outcome was myocardial viability, determined by the retrospective observation of functional recovery. RESULTS: Forty participants underwent baseline physiology, cardiac magnetic resonance imaging, and echocardiography, and 30 had echocardiography at 6 months; 21/42 territories were viable on follow-up echocardiography. Resting backward compression wave energy was significantly greater in viable than in nonviable territories (-5240±3772 versus -1873±1605 W m-2 s-1, P<0.001), and had comparable accuracy to cardiac magnetic resonance imaging for predicting viability (area under the curve 0.812 versus 0.757, P=0.649); a threshold of -2500 W m-2 s-1 had 86% sensitivity and 76% specificity. CONCLUSIONS: Backward compression wave energy has accuracy similar to that of late-gadolinium-enhanced cardiac magnetic resonance imaging in the prediction of viability. Coronary wave intensity analysis has the potential to streamline the management of ischemic cardiomyopathy, in a manner analogous to the effect of fractional flow reserve on the management of stable angina.
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Cardiomiopatías , Reserva del Flujo Fraccional Miocárdico , Isquemia Miocárdica , Disfunción Ventricular Izquierda , Humanos , Volumen Sistólico , Estudios Retrospectivos , Gadolinio , Función Ventricular Izquierda , Resultado del Tratamiento , Miocardio , Isquemia Miocárdica/diagnóstico , Cardiomiopatías/patologíaRESUMEN
Staphylococcus aureus sortase A is a transpeptidase that has been extensively exploited for site-specific modification of proteins and was originally used to attach a labeling reagent containing an LPXTG recognition sequence to a protein or peptide with an N-terminal glycine. Sortase mutants with other recognition sequences have also been reported, but in all cases, the reversibility of the transpeptidation reaction limits the efficiency of sortase-mediated labeling reactions. For the wildtype sortase, depsipeptide substrates, in which the scissile peptide bond is replaced with an ester, allow effectively irreversible sortase-mediated labeling as the alcohol byproduct is a poor competing nucleophile. In this paper, the use of depsipeptide substrates for evolved sortase variants is reported. Substrate specificities of three sortases have been investigated allowing identification of an orthogonal pair of enzymes accepting LPEToG and LPESoG depsipeptides, which have been applied to dual N-terminal labeling of a model protein mutant containing a second, latent N-terminal glycine residue. The method provides an efficient orthogonal site-specific labeling technique that further expands the biochemical protein labeling toolkit.
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Aminoaciltransferasas , Depsipéptidos , Staphylococcus aureus , Aminoaciltransferasas/química , Proteínas Bacterianas/química , Glicina , Indicadores y ReactivosRESUMEN
OBJECTIVE: Many patients presenting with suspected acute coronary syndrome (ACS) have high-sensitivity cardiac troponin (hs-cTn) concentrations between rule-in and rule-out thresholds and hence need serial testing, which is time consuming. The Prospective RandOmised Trial of Emergency Cardiac Computerised Tomography (PROTECCT) assessed the utility of coronary CT angiography (CCTA) in patients with suspected ACS, non-ischaemic ECG and intermediate initial hs-cTn concentration. METHODS: Patients were randomised to CCTA-guided management versus standard of care (SOC). The primary outcome was hospital length of stay (LOS). Secondary outcomes included cost of in-hospital stay and major adverse cardiac events (MACE) at 12 months of follow-up. Data are mean (SD); for LOS harmonic means, IQRs are shown. RESULTS: 250 (aged 55 (14) years, 25% women) patients were randomised. Harmonic mean (IQR) LOS was 7.53 (6.0-9.6) hours in the CCTA arm and 8.14 (6.3-9.8) hours in the SOC arm (p=0.13). Inpatient cost was £1285 (£2216) and £1108 (£3573), respectively, p=0.68. LOS was shorter in the CCTA group in patients with <25% stenosis, compared with SOC; 6.6 (5.6-7.8) hours vs 7.5 (6.1-9.4) hours, respectively; p=0.021. More referrals for cardiology outpatient clinic review and cardiac CT-related outpatient referrals occurred in the SOC arm (p=0.01). 12-month MACE rates were similar between the two arms (7 (5.6%) in the CCTA arm and 8 (6.5%) in the SOC arm-log-rank p=0.78). CONCLUSIONS: CCTA did not lead to reduced hospital LOS or cost, largely because these outcomes were influenced by the detection of ≥25% grade stenosis in a proportion of patients. TRIAL REGISTRATION NUMBER: NCT03583320.
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Síndrome Coronario Agudo , Femenino , Humanos , Masculino , Síndrome Coronario Agudo/diagnóstico por imagen , Síndrome Coronario Agudo/terapia , Dolor en el Pecho/etiología , Angiografía por Tomografía Computarizada , Constricción Patológica/complicaciones , Angiografía Coronaria/métodos , Servicio de Urgencia en Hospital , Estudios ProspectivosRESUMEN
BACKGROUND: Whether revascularization by percutaneous coronary intervention (PCI) can improve event-free survival and left ventricular function in patients with severe ischemic left ventricular systolic dysfunction, as compared with optimal medical therapy (i.e., individually adjusted pharmacologic and device therapy for heart failure) alone, is unknown. METHODS: We randomly assigned patients with a left ventricular ejection fraction of 35% or less, extensive coronary artery disease amenable to PCI, and demonstrable myocardial viability to a strategy of either PCI plus optimal medical therapy (PCI group) or optimal medical therapy alone (optimal-medical-therapy group). The primary composite outcome was death from any cause or hospitalization for heart failure. Major secondary outcomes were left ventricular ejection fraction at 6 and 12 months and quality-of-life scores. RESULTS: A total of 700 patients underwent randomization - 347 were assigned to the PCI group and 353 to the optimal-medical-therapy group. Over a median of 41 months, a primary-outcome event occurred in 129 patients (37.2%) in the PCI group and in 134 patients (38.0%) in the optimal-medical-therapy group (hazard ratio, 0.99; 95% confidence interval [CI], 0.78 to 1.27; P = 0.96). The left ventricular ejection fraction was similar in the two groups at 6 months (mean difference, -1.6 percentage points; 95% CI, -3.7 to 0.5) and at 12 months (mean difference, 0.9 percentage points; 95% CI, -1.7 to 3.4). Quality-of-life scores at 6 and 12 months appeared to favor the PCI group, but the difference had diminished at 24 months. CONCLUSIONS: Among patients with severe ischemic left ventricular systolic dysfunction who received optimal medical therapy, revascularization by PCI did not result in a lower incidence of death from any cause or hospitalization for heart failure. (Funded by the National Institute for Health and Care Research Health Technology Assessment Program; REVIVED-BCIS2 ClinicalTrials.gov number, NCT01920048.).
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Enfermedad de la Arteria Coronaria , Insuficiencia Cardíaca , Intervención Coronaria Percutánea , Disfunción Ventricular Izquierda , Humanos , Insuficiencia Cardíaca/etiología , Insuficiencia Cardíaca/terapia , Volumen Sistólico , Resultado del Tratamiento , Disfunción Ventricular Izquierda/tratamiento farmacológico , Disfunción Ventricular Izquierda/etiología , Disfunción Ventricular Izquierda/mortalidad , Disfunción Ventricular Izquierda/cirugía , Función Ventricular Izquierda , Enfermedad de la Arteria Coronaria/complicaciones , Enfermedad de la Arteria Coronaria/tratamiento farmacológico , Enfermedad de la Arteria Coronaria/mortalidad , Enfermedad de la Arteria Coronaria/cirugía , Fármacos Cardiovasculares/uso terapéutico , Isquemia Miocárdica/tratamiento farmacológico , Isquemia Miocárdica/etiología , Isquemia Miocárdica/mortalidad , Isquemia Miocárdica/cirugíaRESUMEN
While cardiovascular magnetic resonance imaging (CMR) is the gold standard diagnostic test for heart failure etiology, it is not universally available. Our aim was to investigate whether quantifying the extent of coronary disease on angiography can predict the presence of an ischemic etiology. We included 176 patients who underwent CMR and coronary angiography for new heart failure with reduced ejection fraction. Based on CMR, 65% had an ischemic etiology and 35% were non-ischemic. A BCIS jeopardy score threshold ≥6 had 76% sensitivity and 97% specificity. In HFrEF, the extent of coronary disease on angiography can be used to rule in or out an ischemic etiology.
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Enfermedad de la Arteria Coronaria , Insuficiencia Cardíaca , Disfunción Ventricular Izquierda , Angiografía Coronaria/métodos , Enfermedad de la Arteria Coronaria/complicaciones , Enfermedad de la Arteria Coronaria/diagnóstico , Insuficiencia Cardíaca/diagnóstico , Insuficiencia Cardíaca/etiología , Humanos , Valor Predictivo de las Pruebas , Volumen Sistólico , Disfunción Ventricular Izquierda/diagnóstico , Disfunción Ventricular Izquierda/etiología , Función Ventricular IzquierdaRESUMEN
Site-specific protein modification is a widely-used biochemical tool. However, there are many challenges associated with the development of protein modification techniques, in particular, achieving site-specificity, reaction efficiency and versatility. The engineering of peptide ligases and their substrates has been used to address these challenges. This review will focus on sortase, peptidyl asparaginyl ligases (PALs) and variants of subtilisin; detailing how their inherent specificity has been utilised for site-specific protein modification. The review will explore how the engineering of these enzymes and substrates has led to increased reaction efficiency mainly due to enhanced catalytic activity and reduction of reversibility. It will also describe how engineering peptide ligases to broaden their substrate scope is opening up new opportunities to expand the biochemical toolkit, particularly through the development of techniques to conjugate multiple substrates site-specifically onto a protein using orthogonal peptide ligases.
Asunto(s)
Cisteína Endopeptidasas , Ligasas , Proteínas Bacterianas/metabolismo , Catálisis , Cisteína Endopeptidasas/metabolismo , Ligasas/metabolismo , Péptidos/metabolismo , Ingeniería de Proteínas/métodos , Procesamiento Proteico-Postraduccional , Especificidad por SustratoRESUMEN
OBJECTIVES: Cardiovascular disease is one of the leading causes of mortality and morbidity in women. Despite this, even in contemporary research, female patients are poorly represented in trials. This study aimed to explore reasons behind the sex disparity in heart failure (HF) trials. METHODS: HF trials published in seven high-impact clinical journals (impact factor >20), between 2000 and 2020, were identified. Trials with over 300 participants of both sexes were included. Large HF registries, as well as population statistics, were also identified using the same criteria. RESULTS: We identified 146 HF trials, which included 248 620 patients in total. The median proportion of female patients was 25.8%, with the lowest proportions seen in trials enrolling patients with ischaemic cardiomyopathy (17.9%), severe systolic dysfunction (left ventricular ejection fraction (LVEF) <35%) (21.4%) and those involving an invasive procedure (21.1%). The highest proportion of women was seen in trials assessing HF with preserved LVEF (51.6%), as well as trials including older participants (40.5%). Significant differences were seen between prevalence of female trial participants and population prevalence in all LVEF categories (25.8% vs 49.0%, p<0.01). CONCLUSIONS: A significant sex disparity was identified in HF trials, most visible in trials assessing patients with severely reduced LVEF and ischaemic aetiology. This is likely due to a complex interplay between enrolment bias and biological variation. Furthermore, the degree of both these aspects may vary according to trial type. Going forward, we should encourage all HF trials to appraise their recruitment log and suggest reasons for any reported sex disparity.
Asunto(s)
Insuficiencia Cardíaca , Función Ventricular Izquierda , Femenino , Insuficiencia Cardíaca/epidemiología , Insuficiencia Cardíaca/terapia , Humanos , Masculino , Pronóstico , Volumen Sistólico , SístoleRESUMEN
Patients with ischaemic left ventricular dysfunction frequently undergo myocardial viability testing. The historical model presumes that those who have extensive areas of dysfunctional-yet-viable myocardium derive particular benefit from revascularization, whilst those without extensive viability do not. These suppositions rely on the theory of hibernation and are based on data of low quality: taking a dogmatic approach may therefore lead to patients being refused appropriate, prognostically important treatment. Recent data from a sub-study of the randomized STICH trial challenges these historical concepts, as the volume of viable myocardium failed to predict the effectiveness of coronary artery bypass grafting. Should the Heart Team now abandon viability testing, or are new paradigms needed in the way we interpret viability? This state-of-the-art review critically examines the evidence base for viability testing, focusing in particular on the presumed interactions between viability, functional recovery, revascularization and prognosis which underly the traditional model. We consider whether viability should relate solely to dysfunctional myocardium or be considered more broadly and explore wider uses of viability testingoutside of revascularization decision-making. Finally, we look forward to ongoing and future randomized trials, which will shape evidence-based clinical practice in the future.