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AIMS: Women with angina and non-obstructive coronary artery disease (ANOCA) have a heightened risk for cardiovascular events, and the pathophysiology for ischaemic symptoms may be related to alterations in microvascular structure and function. We examined the use of breathing-enhanced oxygenation-sensitive cardiac magnetic resonance imaging (OS-CMR) using vasoactive breathing manoeuvres to assess myocardial oxygenation in women with ANOCA. METHODS AND RESULTS: We recruited women (aged 40-65 years) from two sites in Canada who presented to healthcare with persistent retrosternal chest pain and found to have ANOCA, or without a history of cardiovascular disease. All participants were scanned using a clinical 3T MRI scanner, and OS-CMR images were acquired over a breath hold following paced hyperventilation to measure global and regional measurements of heterogeneity. Fifty-four women with ANOCA (age: 55 ± 6.2 years) and 48 healthy controls (age: 51.2 ± 4.8 years) were recruited. There was no significant difference in volume, function, mass, or global myocardial oxygenation between the two groups [mean %Δ in signal intensity (SI): 4.9 (±7.3) vs. 4.5 (±10.1), P = 0.82]. Women with ANOCA had higher regional variations in myocardial oxygenation in circumferential [median %Δ in SI: 5.1 (2.0-7.6) vs. 2.2 (1.4-3.5), P = 0.0004] and longitudinal directions [median %Δ in SI: 11.4 (5.4-16.7) vs. 6.0 (3.0-7.0), P = 0.001], which remained present in a multivariate model. CONCLUSION: Heterogeneous myocardial oxygenation may explain ischaemic symptoms without any associated epicardial obstructive coronary artery disease. Regional variations in myocardial oxygenation on OS-CMR could serve as an important diagnostic marker for microvascular dysfunction in women with ANOCA.
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Angina de Pecho , Enfermedad de la Arteria Coronaria , Imagen por Resonancia Cinemagnética , Humanos , Femenino , Persona de Mediana Edad , Enfermedad de la Arteria Coronaria/diagnóstico por imagen , Enfermedad de la Arteria Coronaria/fisiopatología , Adulto , Angina de Pecho/diagnóstico por imagen , Angina de Pecho/fisiopatología , Anciano , Imagen por Resonancia Cinemagnética/métodos , Estudios de Casos y Controles , Canadá , Consumo de Oxígeno/fisiología , Vasos Coronarios/diagnóstico por imagen , Vasos Coronarios/fisiopatología , Circulación Coronaria/fisiologíaRESUMEN
Background: Type 2 myocardial infarction (T2MI) occurs when myocardial oxygen demand exceeds myocardial oxygen supply. T2MIs occur more frequently and have worse outcomes compared to Type 1 myocardial infarction caused by an acute plaque rupture. No clinical trial evidence is available to guide pharmacological therapies in this high-risk population. Methods: The Rivaroxaban in Type 2 Myocardial Infarction (R2MI) trial (NCT04838808) was a trainee-led, pragmatic, pilot study that randomised patients with a T2MI to either rivaroxaban 2.5 mg twice daily or placebo. The trial was stopped early due to low recruitment. Investigators explored the challenges of conducting the trial in this population. This was supplemented by a retrospective chart review of 10,000 consecutive troponin assays undertaken during the study period. Results: Over a 1-year period, 276 patients with T2MI were screened for inclusion of which only 7 (2.5%) were randomised in the trial. Study investigators identified trial design and participant population factors that limited recruitment. These included: heterogeneity of patient presentation, poor clinical prognosis, and lack of dedicated non-trainee study personnel. The major limitation to recruitment was the frequency of identified exclusion criterion. The retrospective chart review identified 1715 patients with an elevated high-sensitivity troponin level, of which 916 (53%) were adjudicated to be related to T2MI. Of these, 94.5% possessed an exclusion criterion for the trial. Conclusion: Patients with a T2MI are challenging to recruit into clinical trials involving oral anticoagulation. Future studies should account for only â¼1 in every 20 screened individuals being a candidate for study recruitment.
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BACKGROUND: Renin-angiotensin aldosterone system inhibitors (RAASi) are commonly used among patients hospitalized with a severe acute respiratory syndrome coronavirus 2 infection coronavirus disease 2019 (COVID-19). We evaluated whether continuation versus discontinuation of RAASi were associated with short term clinical or biochemical outcomes. METHODS: The RAAS-COVID-19 trial was a randomized, open label study in adult patients previously treated with RAASi who are hospitalized with COVID-19 (NCT04508985). Participants were randomized 1:1 to discontinue or continue RAASi. The primary outcome was a global rank score calculated from baseline to day 7 (or discharge) incorporating clinical events and biomarker changes. Global rank scores were compared between groups using the Wilcoxon test statistic and the negative binomial test (using incident rate ratio [IRR]) and the intention-to-treat principle. RESULTS: Overall, 46 participants were enrolled; 21 participants were randomized to discontinue RAASi and 25 to continue. Patients' mean age was 71.5 years and 43.5% were female. Discontinuation of RAASi, versus continuation, resulted in a non-statistically different mean global rank score (discontinuation 6 [standard deviation [SD] 6.3] vs continuation 3.8 (SD 2.5); P = .60). The negative binomial analysis identified that discontinuation increased the risk of adverse outcomes (IRR 1.67 [95% CI 1.06-2.62]; P = .027); RAASi discontinuation increased brain natriuretic peptide levels (% change from baseline: +16.7% vs -27.5%; P = .024) and the incidence of acute heart failure (33% vs 4.2%, P = .016). CONCLUSION: RAASi continuation in participants hospitalized with COVID-19 appears safe; discontinuation increased brain natriuretic peptide levels and may increase risk of acute heart failure; where possible, RAASi should be continued.
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COVID-19 , Insuficiencia Cardíaca , Adulto , Anciano , Aldosterona , Antagonistas de Receptores de Angiotensina/efectos adversos , Inhibidores de la Enzima Convertidora de Angiotensina/efectos adversos , Antihipertensivos/uso terapéutico , Femenino , Insuficiencia Cardíaca/tratamiento farmacológico , Hospitales , Humanos , Péptido Natriurético Encefálico , Sistema Renina-AngiotensinaRESUMEN
BACKGROUND: Actigraphy-based measurements of physiologic parameters may enable design of patient-centric heart failure (HF) clinical trials. Recently, the Heart Failure Collaboratory focused on recommendations for meaningful change and use of actigraphy as an end point in HF clinical trials. We aimed to evaluate randomized controlled trials (RCTs) that have quantified the impact of HF interventions using actigraphy. METHODS: Using a scoping review strategy, we evaluated the use of actigraphy in HF RCTs. Studies were identified through electronic searches of Embase, OVID Medline, PubMed, and Cochrane Review. Data on trial characteristics and results were collected. RESULTS: We identified 11 RCTs with a total of 1,455 participants. The risk of bias across the included trials was high overall. All trials had the primary outcomes reflecting measures of either physical activity (n = 8), sleep (n = 2), or both (n = 1). Five trials evaluated response to pharmacologic therapies compared with placebo, 3 evaluated physical activity interventions, 2 evaluated group or cognitive therapy, and 1 evaluated sleep-ventilation strategy. Sample sizes ranged from 30 to 619 participants. There was significant heterogeneity relating to device type, body placement site, and handling of missing actigraphy data. Duration of monitoring ranged from 48 hours to 12 weeks. None of the studies evaluating pharmacologic therapies (n = 5) demonstrated a significant improvement of actigraphy-based primary end point measurements. CONCLUSIONS: There is significant heterogeneity in the use, methodology, and results of actigraphy-based HF RCTs. Our results highlight the need to develop, standardize, and validate actigraphy-specific outcomes for use in HF clinical trials.
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Actigrafía , Insuficiencia Cardíaca , Ensayos Clínicos Controlados Aleatorios como Asunto , Dispositivos Electrónicos Vestibles , HumanosRESUMEN
BACKGROUND: An effective and safe oral anticoagulation (OAC) strategy for patients with new postoperative AF (POAF) after noncardiac surgery remains unclear. We aimed to determine the association between OAC use and 1) thromboembolic events and 2) major bleeding in patients with POAF after noncardiac surgery. METHODS: A retrospective cohort (1999-2015) was used to identify patients with new POAF after inpatient noncardiac surgery. Initiation of OAC was defined as prescription of an OAC within 30 days following hospital discharge. Times to first hospital admission or emergency department visit for a thromboembolic or major bleeding event were compared using Cox proportional hazards models. RESULTS: We identified 22,007 patients with new POAF after inpatient noncardiac surgery. The majority of patients had intermediate (CHA2DS2-VASc 2-3: 45%) to high (CHA2DS2-VASc ≥ 4: 42%) thromboembolic risk. During a mean follow-up of 4 years, a total of 1099 (5%) thromboembolic and 3250 (15%) bleeding events occurred. Compared with patients not on anticoagulation, anticoagulation did not reduce the risk for thromboembolic events (adjusted hazard ratio [aHR] 0.89, 95% CI 0.73-1.07). In patients initiated on anticoagulation, there was an association with a higher risk for major bleeding (aHR 1.14, 95% CI 1.04-1.25). CONCLUSIONS: In patients with new POAF after noncardiac surgery, anticoagulation was not associated with a reduction in long-term thromboembolic events; however, this was accompanied by an overall increased risk for major bleeding. Future prospective clinical studies are needed to better address the role for anticoagulation therapy in the setting of POAF after noncardiac surgery to understand the efficacy and safety of treatment.
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Anticoagulantes , Fibrilación Atrial , Hemorragia , Efectos Adversos a Largo Plazo , Complicaciones Posoperatorias , Procedimientos Quirúrgicos Operativos/efectos adversos , Tromboembolia , Anciano , Anticoagulantes/administración & dosificación , Anticoagulantes/efectos adversos , Fibrilación Atrial/diagnóstico , Fibrilación Atrial/tratamiento farmacológico , Fibrilación Atrial/epidemiología , Fibrilación Atrial/etiología , Canadá/epidemiología , Femenino , Estudios de Seguimiento , Hemorragia/inducido químicamente , Hemorragia/epidemiología , Humanos , Pacientes Internos/estadística & datos numéricos , Efectos Adversos a Largo Plazo/epidemiología , Efectos Adversos a Largo Plazo/etiología , Efectos Adversos a Largo Plazo/prevención & control , Masculino , Complicaciones Posoperatorias/diagnóstico , Complicaciones Posoperatorias/tratamiento farmacológico , Modelos de Riesgos Proporcionales , Estudios Retrospectivos , Medición de Riesgo/métodos , Medición de Riesgo/estadística & datos numéricos , Tromboembolia/epidemiología , Tromboembolia/etiología , Tromboembolia/prevención & controlRESUMEN
AIM: To investigate the ability of the Thrombolysis in Myocardial Infarction Risk Score for Heart Failure in Diabetes (TRS-HFDM ) to stratify patients with type 2 diabetes mellitus (T2DM) and high cardiovascular risk for heart failure (HF) hospitalization. MATERIALS AND METHODS: We used data from the control group of the Action to Control Cardiovascular Risk in Diabetes Study Group (ACCORD) trial (n = 5123; mean follow-up 4.8 years). The TRS-HFDM includes: prior HF (2 points), atrial fibrillation (1 point), coronary artery disease (1 point), estimated glomerular filtration rate <60 mL/min/1.73 m2 (1 point), and urine albumin-to-creatinine ratio (>300 mg/g: 2 points; 30-300 mg/g: 1 point). We evaluated the discrimination (Harrell's C-index) and calibration (Nam-D'Agostino calibration statistic) of the TRS-HFDM with regard to time to HF hospitalization or death due to HF. RESULTS: The mean age of the participants was 62.8 ± 6.6 years, and 38% were women. The prevalences of TRS-HFDM 0, 1, 2, 3 and ≥4 were 42.1%, 34.9%, 14.6%, 6.0% and 2.5%, respectively. Increasing TRS-HFDM corresponded to an increasing HF risk: 1.3 per 1000 person-years for a TRS-HFDM of 0 to 64.7 per 1000 person-years for TRS-HFDM of ≥4. The TRS-HFDM demonstrated robust discrimination of HF outcomes (C-index 0.78). Furthermore, the score was well calibrated for HF outcomes (calibration statistic P = 0.13). Similar results were seen in participants without baseline HF (C-index 0.75). CONCLUSION: The TRS-HFDM discriminates HF-specific risk among people with T2DM. The use of TRS-HFDM to identify those who would maximally benefit from therapies that reduce HF risk warrants evaluation.
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Diabetes Mellitus Tipo 2 , Insuficiencia Cardíaca , Infarto del Miocardio , Anciano , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Diabetes Mellitus Tipo 2/epidemiología , Femenino , Insuficiencia Cardíaca/epidemiología , Humanos , Persona de Mediana Edad , Infarto del Miocardio/epidemiología , Infarto del Miocardio/prevención & control , Medición de Riesgo , Factores de Riesgo , Terapia TrombolíticaRESUMEN
BACKGROUND: The timing of enrolment following an acute coronary syndrome (ACS) may influence cardiovascular (CV) outcomes and potentially treatment effect in clinical trials. Understanding the timing and type of clinical events after an ACS will allow for clinicians to better tailor evidence-based treatments to optimize therapeutic effect. Using a large contemporary trial in patients with type 2 diabetes mellitus (T2DM) post-ACS, we examined the impact of timing of enrolment on subsequent CV outcomes. METHODS: EXAMINE was a randomized trial of alogliptin versus placebo in 5,380 patients with T2DM and a recent ACS from October 2009 to March 2013. The primary outcome was a composite of CV death, nonfatal myocardial infarction (MI), or nonfatal stroke. The median follow-up was 18â¯months. In this post hoc analysis, we examined the occurrence of subsequent CV events by timing of enrollment divided by tertiles of time from ACS to randomization: 8-34, 35-56, and 57-141â¯days. RESULTS: Patients randomized early (compared to the latest times) had less comorbidities at baseline including a history of heart failure (HF; 24.7% vs 33.0%), prior coronary artery bypass graft (9.6% vs 15.9%), or atrial fibrillation (5.9% vs 9.4%). Despite the reduced comorbidity burden, the risk of the primary outcome was highest in patients randomized early compared to the latest time (adjusted hazard ratio 1.47; 95% CI 1.21-1.74). Similarly, patients randomized early had an increased risk of recurrent MI (adjusted hazard ratio 1.51; 95% CI 1.17-1.96) and HF hospitalization (1.49; 95% CI 1.05-2.10). CONCLUSIONS: In a contemporary cohort of T2DM with a recent ACS, the risk for recurrent CV events including MI and HF hospitalization is elevated early after an ACS. Given the emergence of antihyperglycemic therapies that reduce the risk of MI and HF among patients with T2DM at high CV risk, future studies evaluating the initiation of these therapies in the early period following an ACS are warranted given the large burden of potentially modifiable CV events.
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Síndrome Coronario Agudo , Diabetes Mellitus Tipo 2 , Infarto del Miocardio , Selección de Paciente , Piperidinas , Distribución Aleatoria , Accidente Cerebrovascular , Factores de Tiempo , Uracilo/análogos & derivados , Síndrome Coronario Agudo/complicaciones , Síndrome Coronario Agudo/terapia , Comorbilidad , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Práctica Clínica Basada en la Evidencia/métodos , Práctica Clínica Basada en la Evidencia/normas , Femenino , Factores de Riesgo de Enfermedad Cardiaca , Humanos , Hipoglucemiantes/administración & dosificación , Hipoglucemiantes/efectos adversos , Masculino , Persona de Mediana Edad , Infarto del Miocardio/diagnóstico , Infarto del Miocardio/etiología , Infarto del Miocardio/mortalidad , Evaluación de Procesos y Resultados en Atención de Salud , Piperidinas/administración & dosificación , Piperidinas/efectos adversos , Medición de Riesgo/métodos , Medición de Riesgo/estadística & datos numéricos , Accidente Cerebrovascular/diagnóstico , Accidente Cerebrovascular/etiología , Accidente Cerebrovascular/mortalidad , Uracilo/administración & dosificación , Uracilo/efectos adversosAsunto(s)
Síndrome Coronario Agudo , Diabetes Mellitus Tipo 2 , Insuficiencia Cardíaca , Hiperglucemia , Síndrome Coronario Agudo/epidemiología , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/epidemiología , Insuficiencia Cardíaca/epidemiología , Insuficiencia Cardíaca/etiología , Humanos , Volumen SistólicoRESUMEN
BACKGROUND: Recent randomized control trials have described a protective cardiovascular effect of novel glucose lowering drugs in patients at high cardiovascular risk. Whether these second-line agents have similar effects in the general population is unknown. We aimed to compare the risk of major cardiovascular and adverse events in new users of sodium-glucose cotransporter-2 inhibitors (SGLT-2i), dipeptidyl peptidase-4 inhibitor (DPP-4i), glucagon-like peptide 1 agonist (GLP-1a), and sulfonylurea in T2DM patients not controlled on metformin therapy. METHODS: Retrospective cohort study using the MarketScan database (2011-2015). We selected T2DM individuals who were newly dispensed sulfonylureas, SGLT-2i, DPP-4i, or GLP-1a, as second-line therapy, added to metformin. Cohort entry was defined by date of first prescription of the second-line agent. Time to first non-fatal cardiovascular or adverse event was compared using Cox regression models adjusted for confounders. RESULTS: Among 118,341 T2DM patients using metformin (mean age: 56), most were at low cardiovascular risk (4% with previous cardiovascular or cerebrovascular event). During a median follow-up of 10 months compared with sulfonylureas users, cardiovascular risk was lower in users of SGLT-2i (aHR = 0.61; 95% CI: 0.40-0.97), DPP-4i (aHR = 0.79; 95% CI: 0.69-0.90) and GLP-1a (aHR = 0.65; 95% CI: 0.48-0.89). Serious adverse events were rare but compared with sulfonylurea, the risk was lower in new users of novel glucose lowering agents. CONCLUSION: In our analyses, which included patients with and without prior cardiovascular disease, initiating novel glucose lowering drugs as second-line therapy for T2DM was associated with a lower risk of cardiovascular and adverse events than sulfonylurea initiation.
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Enfermedades Cardiovasculares , Diabetes Mellitus Tipo 2 , Inhibidores de la Dipeptidil-Peptidasa IV , Metformina , Inhibidores del Cotransportador de Sodio-Glucosa 2 , Enfermedades Cardiovasculares/inducido químicamente , Enfermedades Cardiovasculares/diagnóstico , Enfermedades Cardiovasculares/epidemiología , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Diabetes Mellitus Tipo 2/epidemiología , Inhibidores de la Dipeptidil-Peptidasa IV/efectos adversos , Glucosa , Humanos , Hipoglucemiantes/efectos adversos , Persona de Mediana Edad , Estudios RetrospectivosRESUMEN
Background Randomized controlled trials showed that newer glucose-lowering agents are cardioprotective, but most participants were men. It is unknown whether benefits are similar in women. Methods and Results Among adults with type 2 diabetes mellitus not controlled with metformin with no prior use of insulin, we assessed for sex differences in the cardiovascular effectiveness and safety of sodium-glucose-like transport-2 inhibitors (SGLT-2i), glucagon-like peptide-1 receptor agonists (GLP-1RA), dipeptidyl peptidase-4 inhibitors, initiated as second-line agents relative to sulfonylureas (reference-group). We studied type 2 diabetes mellitus American adults with newly dispensed sulfonylureas, SGLT-2i, GLP-1RA, or dipeptidyl peptidase-4 inhibitors (Marketscan-Database: 2011-2017). We used multivariable Cox proportional hazards models with time-varying exposure to compare time to first nonfatal cardiovascular event (myocardial infarction/unstable angina, stroke, and heart failure), and safety outcomes between drugs users, and tested for sex-drug interactions. Among 167 254 type 2 diabetes mellitus metformin users (46% women, median age 59 years, at low cardiovascular risk), during a median 4.5-year follow-up, cardiovascular events incidence was lower in women than men (14.7 versus 16.7 per 1000-person-year). Compared with sulfonylureas, hazard ratios (HRs) for cardiovascular events were lower with GLP-1RA (adjusted HR-women: 0.57, 95% CI: 0.48-0.68; aHR-men: 0.82, 0.71-0.95), dipeptidyl peptidase-4 inhibitors (aHR-women: 0.83, 0.77-0.89; aHR-men: 0.85, 0.79-0.91) and SGLT-2i (aHR-women: 0.58, 0.46-0.74; aHR-men: 0.69, 0.57-0.83). A sex-by-drug interaction was statistically significant only for GLP-1RA (P=0.002), suggesting greater cardiovascular effectiveness in women. Compared with sulfonylureas, risks of adverse events were similarly lower in both sexes for GLP-1RA (aHR-women: 0.81, 0.73-0.89; aHR-men: 0.80, 0.71-0.89), dipeptidyl peptidase-4 inhibitors (aHR-women: 0.82, 0.78-0.87; aHR-men: 0.83, 0.78-0.87) and SGLT-2i (aHR-women: 0.68, 0.59-0.78; aHR-men: 0.67, 0.59-0.78) (all sex-drug interactions for adverse events P>0.05). Conclusions Newer glucose-lowering drugs were associated with lower risk of cardiovascular events than sulfonylureas, with greater effectiveness of GLP-1RA in women than men. Overall, they appeared safe, with a better safety profile for SGLT-2i than for GLP-1RA regardless of sex.
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Glucemia/efectos de los fármacos , Enfermedades Cardiovasculares/prevención & control , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Inhibidores de la Dipeptidil-Peptidasa IV/uso terapéutico , Hipoglucemiantes/uso terapéutico , Incretinas/uso terapéutico , Metformina/uso terapéutico , Inhibidores del Cotransportador de Sodio-Glucosa 2/uso terapéutico , Anciano , Biomarcadores/sangre , Glucemia/metabolismo , Enfermedades Cardiovasculares/diagnóstico , Enfermedades Cardiovasculares/epidemiología , Bases de Datos Factuales , Diabetes Mellitus Tipo 2/sangre , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/epidemiología , Regulación hacia Abajo , Quimioterapia Combinada , Femenino , Receptor del Péptido 1 Similar al Glucagón/agonistas , Factores de Riesgo de Enfermedad Cardiaca , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Medición de Riesgo , Factores Sexuales , Resultado del TratamientoRESUMEN
The aim of this systematic review was to assess dysregulated miRNA biomarkers in coronary artery disease (CAD). Dysregulated microRNA (miRNAs) have been shown to be linked to cardiovascular pathologies including CAD and may have utility as diagnostic and prognostic biomarkers. We compared miRNAs identified in acute coronary syndrome (ACS) compared with stable CAD and control populations. We conducted a systematic search of controlled vocabulary and free text terms related to ACS, stable CAD and miRNA in Biosis Previews (OvidSP), The Cochrane Library (Wiley), Embase (OvidSP), Global Health (OvidSP), Medline (PubMed and OvidSP), Web of Science (Clarivate Analytics), and ClinicalTrials.gov which yielded 7370 articles. Of these, 140 original articles were appropriate for data extraction. The most frequently reported miRNAs in any CAD (miR-1, miR-133a, miR-208a/b, and miR-499) are expressed abundantly in the heart and play crucial roles in cardiac physiology. In studies comparing ACS cases with stable CAD patients, miR-21, miR-208a/b, miR-133a/b, miR-30 family, miR-19, and miR-20 were most frequently reported to be dysregulated in ACS. While a number of miRNAs feature consistently across studies in their expression in both ACS and stable CAD, when compared with controls, certain miRNAs were reported as biomarkers specifically in ACS (miR-499, miR-1, miR-133a/b, and miR-208a/b) and stable CAD (miR-215, miR-487a, and miR-502). Thus, miR-21, miR-133, and miR-499 appear to have the most potential as biomarkers to differentiate the diagnosis of ACS from stable CAD, especially miR-499 which showed a correlation between the level of their concentration gradient and myocardial damage. Although these miRNAs are potential diagnostic biomarkers, these findings should be interpreted with caution as the majority of studies conducted predefined candidate-driven assessments of a limited number of miRNAs (PROSPERO registration: CRD42017079744).
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Síndrome Coronario Agudo/sangre , MicroARN Circulante/sangre , Enfermedad de la Arteria Coronaria/sangre , Síndrome Coronario Agudo/diagnóstico , Síndrome Coronario Agudo/genética , Adulto , Anciano , Anciano de 80 o más Años , Biomarcadores/sangre , MicroARN Circulante/genética , Enfermedad de la Arteria Coronaria/diagnóstico , Enfermedad de la Arteria Coronaria/genética , Femenino , Regulación de la Expresión Génica , Humanos , Masculino , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Pronóstico , Reproducibilidad de los ResultadosRESUMEN
Preeclampsia increases a woman's risk of stroke and leads to short-term cognitive complaints. Our objective was to assess the impact of preeclampsia on long-term cognitive performance. This is a retrospective cohort study using data from the Coronary Artery Risk Development in Young Adults cohort of healthy individuals (18-30 years) recruited from the general population in 3 cities in the United States, followed for 25 years (1985-2010). Psychomotor speed (Digit Symbol Substitution Test), executive function (Stroop Test), and memory (Rey Auditory Verbal Learning Test) were contrasted between women with and without preeclampsia using multivariate linear regression. We included 568 parous women (193 with preeclampsia and 375 with normotensive pregnancy) without baseline neurological disease or depression matched according to delivery period. Approximately 18 years after delivery, preeclamptic women scored significantly lower on Digit Symbol Substitution Test than women with normotensive pregnancy (73.21±14.79 versus 75.87±15.22; P=0.047) and on the third trial of Stroop Test (correct answers: 38.85±3.62 versus 39.42±1.87; P=0.014; completion time: 44.02±10.48 versus 41.62±10.61 seconds; P=0.01), but there were no differences in Rey Auditory Verbal Learning Test. These differences were attenuated after adjustment for age, body mass index, hypertension, education, and depression. Similar differences in neurocognitive scores were noted between women with other hypertensive disorders of pregnancy and normotensive pregnancy. Hypertension in pregnancy does not seem to be independently associated with neurocognitive impairment later in life.
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Cognición/fisiología , Función Ejecutiva/fisiología , Memoria/fisiología , Preeclampsia/psicología , Adolescente , Adulto , Presión Sanguínea/fisiología , Femenino , Humanos , Pruebas Neuropsicológicas , Embarazo , Tiempo de Reacción/fisiología , Estudios Retrospectivos , Aprendizaje Verbal/fisiología , Adulto JovenAsunto(s)
Anemia Hemolítica/diagnóstico , Deficiencia de Vitamina B 12/diagnóstico , Adulto , Anemia Hemolítica/etiología , Anemia Hemolítica/fisiopatología , Diagnóstico Diferencial , Fatiga/etiología , Femenino , Humanos , Vitamina B 12/sangre , Deficiencia de Vitamina B 12/complicaciones , Vómitos/etiologíaRESUMEN
OBJECTIVE: To systematically review and summarize studies investigating an association between a history of preeclampsia and cognitive function later in life. DATA SOURCES: Studies published before August 2017 were identified without any language restriction or study design limits through electronic searches of 10 main databases including MEDLINE and ClinicalTrials.gov. METHODS OF STUDY SELECTION: We considered all observational studies that included preeclampsia as a clearly defined prespecified risk factor and that examined a cognition-related outcome measure including validated cognitive tests, magnetic resonance brain imaging, or a clinical diagnosis of dementia. Study quality was assessed using the New-Castle Ottawa scale. All review stages were conducted independently by two reviewers, and disagreement was resolved by a third reviewer. Where possible, data were pooled using a random-effects model. TABULATION, INTEGRATION, AND RESULTS: Of 3,126 potentially relevant studies, 13 were included in our review (1,314 women with prior preeclampsia and 289,080 women with prior normotensive pregnancy); median time since pregnancy was 6 years. A higher number of self-reported deficits in perception, memory, and motor functioning on the Cognitive Failure Questionnaire was reported in women with vs without prior preeclamptic pregnancies (Cognitive Failure Questionnaire mean total score 41.5 vs 36.8 out of 100, weighted mean difference of -5.1 points [-9.4 to -0.8]). Our meta-analysis did not reveal significant differences in studies assessing attention (Digit Symbol Substitution or Coding); however, women with preeclampsia performed worse on one of two meta-analyzed tests assessing memory (Letter Number Sequencing mean total score: 10.6 vs 10.1 out of 21, weighted mean difference of 0.63 points 0.06-1.2). Pooling of cognitive outcome measures for studies assessing brain imaging or a clinical diagnosis of dementia were limited by differences in reporting and marked heterogeneity between studies. CONCLUSION: Although preeclampsia is associated with subjective cognitive symptoms, our systematic review did not demonstrate clear evidence of impairment on standard neurocognitive tests. There is a paucity of high-quality studies assessing cognitive outcomes after preeclampsia.
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Disfunción Cognitiva/epidemiología , Preeclampsia/psicología , Disfunción Cognitiva/diagnóstico , Femenino , Humanos , Memoria , Pruebas de Estado Mental y Demencia , Percepción , Embarazo , AutoinformeRESUMEN
BACKGROUND: Premature myocardial infarction (MI) is an increasingly prevalent cause of morbidity and mortality worldwide. A subset of patients, predominantly young women, present with MI with no obstructive coronary artery disease (MINOCA), a nomenclature gaining recognition. However, few data exist on presentation and prognosis according to the severity of coronary artery disease (CAD). METHODS: We studied patients with premature (younger than 55 years of age) acute MI enrolled in a large cohort in 24 centres across Canada. Baseline clinical, psychosocial, and coronary anatomy characteristics as well as 12-month outcomes were compared between patients with MINOCA (< 50% stenosis) and patients with MI with obstructive CAD (≥ 50% stenosis; MICAD). RESULTS: From a cohort of 1210 patients with acute coronary syndrome, we examined 998 MI patients with available angiography core lab readings: 82 (8.2%) had a MINOCA and 916 (91.8%) had a MICAD. Forty percent of patients with MINOCA were women compared with one-third with MICAD. The prevalence of traditional risk factors and chest pain at presentation was lower in MINOCA patients, yet 37% had a ST-elevation MI and 10% presented with a cardiac arrest. No evident etiology was detected in > 70% of MINOCA, but 10% presented with either spontaneous coronary dissection or Takotsubo cardiomyopathy. Although combined major adverse cardiovascular events and all-cause readmission rate was lower in the MINOCA group (14% vs 25%; adjusted hazard ratio, 0.51; 95% confidence interval, 0.28-0.93), it was not negligible. CONCLUSIONS: Patients with MINOCA present with high-risk features despite the absence of obstructive CAD. A search for etiology and eventual treatment provides a rich avenue for improving prognosis in young women with premature MI.
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Vasos Coronarios , Disección Aórtica/complicaciones , Disección Aórtica/diagnóstico por imagen , Canadá/epidemiología , Angiografía Coronaria/métodos , Oclusión Coronaria/complicaciones , Oclusión Coronaria/diagnóstico por imagen , Vasos Coronarios/diagnóstico por imagen , Vasos Coronarios/patología , Femenino , Humanos , Persona de Mediana Edad , Infarto del Miocardio/diagnóstico , Infarto del Miocardio/epidemiología , Infarto del Miocardio/etiología , Infarto del Miocardio/psicología , Evaluación de Resultado en la Atención de Salud , Pronóstico , Psicología , Cardiomiopatía de Takotsubo/complicaciones , Cardiomiopatía de Takotsubo/diagnósticoRESUMEN
BACKGROUND: As health care delivery increasingly requires providers to cross international borders, medical students at McGill University, Canada, developed a multidirectional exchange program with Haiti and Rwanda. The program integrates surgery, pathology, anatomy, research methodology, and medical education. OBJECTIVE: The aim of the present study was to explore the global health value of this international training program to improve medical education within the environment of developing countries, such as Haiti and Rwanda, while improving sociocultural learning of Canadian students. METHODS: Students from the University of Kigali, Rwanda and Université Quisqueya, Haiti, participated in a 3-week program at McGill University. The students spanned from the first to sixth year of their respective medical training. The program consisted of anatomy dissections, surgical simulations, clinical pathology shadowing, and interactive sessions in research methodology and medical education. To evaluate the program, a survey was administered to students using a mixed methodology approach. FINDINGS: Common benefits pointed out by the participants included personal and professional growth. The exchange improved career development, sense of responsibility toward one's own community, teaching skills, and sociocultural awareness. The participants all agreed that the anatomy dissections improved their knowledge of anatomy and would make them more comfortable teaching the material when the returned to their university. The clinical simulation activities and shadowing experiences allowed them to integrate the different disciplines. However, the students all felt the research component had too little time devoted to it and that the knowledge presented was beyond their educational level. CONCLUSION: The development of an integrated international program in surgery, pathology, anatomy, research methodology, and medical education provided medical students with an opportunity to learn about differences in health care and medical education between the 3 countries. This exchange demonstrated that a crosscultural near-peer teaching environment can be an effective and sustainable method of medical student-centered development in global health.
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Anatomía/educación , Cirugía General/educación , Salud Global , Patología/educación , Grupo Paritario , Proyectos de Investigación , Estudiantes de Medicina , Canadá , Curriculum , Educación de Pregrado en Medicina , Haití , Humanos , Modelos Educacionales , Evaluación de Programas y Proyectos de Salud , RwandaRESUMEN
BACKGROUND: With the introduction of new treatment paradigms for esophageal perforation, the management of this highly morbid condition is evolving. We reviewed our experience to investigate the modern management and outcomes of esophageal perforations with a focus on operatively repaired patients. METHODS: A retrospective review of all esophageal perforations was conducted between August 2003 and January 2016. RESULTS: A total of 48 patients were identified, with iatrogenic injury in 19 (40%), spontaneous perforation in 18 (38%), and traumatic/foreign body causes in 11 (23%). The distal esophagus was the site of perforation in 63% of the patients, and the duration of time between perforation and treatment was <24 hours in 60%. Nonoperative management was employed in 18 (38%) and operative repair in 30 (primary operative repair = 20, drainage = 4, esophagectomy = 6). Iatrogenic and traumatic perforations were more likely to be treated nonoperatively (68%), while all spontaneous perforations were treated by operative intervention. There were no complications or mortalities in the nonoperative group and only a 5% reintervention rate. In the operative group, complications occurred in 10 (33%), reinterventions in 13 (43%), and mortality in 2 (7%) patients. CONCLUSION: Our study highlights the importance of considering the etiology of a perforation when planning management and the success of nonoperative treatment with careful patient selection. In addition, operative repair in septic patients yielded excellent outcomes and should be the standard for comparison in future studies exploring endoscopic approaches.
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Tratamiento Conservador/métodos , Perforación del Esófago/cirugía , Esofagoscopía/métodos , Adulto , Factores de Edad , Anciano , Estudios de Cohortes , Tratamiento Conservador/mortalidad , Perforación del Esófago/diagnóstico por imagen , Perforación del Esófago/terapia , Esofagectomía/efectos adversos , Esofagectomía/métodos , Esofagoscopía/efectos adversos , Esofagoscopía/tendencias , Femenino , Predicción , Humanos , Masculino , Persona de Mediana Edad , Selección de Paciente , Complicaciones Posoperatorias/mortalidad , Complicaciones Posoperatorias/fisiopatología , Pronóstico , Estudios Retrospectivos , Medición de Riesgo , Índice de Severidad de la Enfermedad , Factores Sexuales , Estadísticas no Paramétricas , Tasa de Supervivencia , Resultado del TratamientoRESUMEN
INTRODUCTION: The clinical significance of perineural invasion (PNI) on prostate needle biopsy is controversial. The aim of this present study is to determine the role of PNI on prostate biopsy in predicting adverse findings at radical prostatectomy in a recent cohort of screen detected prostate cancer. MATERIALS AND METHODS: We analyzed 470 patients diagnosed with prostate cancer from a prospectively maintained database at Princess Margaret Hospital. Out of the 470 patients diagnosed with prostate cancer, 139 underwent radical prostatectomy. Pathological specimens were examined, and perineural invasion was identified as carcinoma tracking along or around a nerve in the perineural space. We investigated the predictive value of PNI on biopsy with PNI on radical prostatectomy as well as the ability of PNI on prostate biopsy to predict adverse findings at radical prostatectomy. RESULTS: Perineural invasion was present in 124 (26%) of biopsy specimens diagnosed with prostate cancer and 94 (68%) of those who chose radical prostatectomy. Perineural invasion on prostate needle biopsy was not predictive of radical prostatectomy Gleason score (p = .377), pathological stage (p = .852), extraprostatic extension (p = .258), surgical margin (p = .079), lymphovascular invasion (p = .499), and upgrading (p = .514) or downgrading (p = .208) at radical prostatectomy. The sensitivity, specificity, positive predictive value, and negative predictive value of PNI on biopsy for PNI on radical prostatectomy were 32%, 82%, 79%, and 37% respectively. The Cohen's Kappa correlation coefficient was .11. CONCLUSIONS: Perineural invasion on prostate needle biopsy is not predictive of radical prostatectomy outcome. Furthermore, perineural invasion on biopsy has limited predictive value for perineural invasion at radical prostatectomy.