Effectiveness and safety of integrase strand transfer inhibitors in Spain: a prospective real-world study

IntroductionSecond-generation integrase strand transfer inhibitors (INSTIs) are preferred treatment options worldwide, and dolutegravir (DTG) is the treatment of choice in resource-limited settings. Nevertheless, in some resource-limited settings, these drugs are not always available. An analysis of the experience with the use of INSTIs in unselected adults living with HIV may be of help to make therapeutic decisions when second-generation INSTIs are not available. This study aimed to evaluate the real-life effectiveness and safety of dolutegravir (DTG), elvitegravir/cobicistat (EVG/c), and raltegravir (RAL) in a large Spanish cohort of HIV-1-infected patients.MethodsReal-world study of adults living with HIV who initiated integrase INSTIs DTG, EVG/c, and RAL-based regimens in three settings (ART-naïve patients, ART-switching, and ART-salvage patients). The primary endpoint was the median time to treatment discontinuation after INSTI-based regimen initiation. Proportion of patients experiencing virological failure (VF) (defined as two consecutive viral loads (VL) ≥200 copies/mL at 24 weeks or as a single determination of VL ≥1,000 copies/mL while receiving DTG, EVG/c or RAL, and at least 3 months after INSTI initiation) and time to VF were also evaluated.ResultsVirological effectiveness of EVG/c- and RAL-based regimens was similar to that of DTG when given as first-line and salvage therapy. Treatment switching for reasons other than virological failure was more frequent in subjects receiving EVG/c and, in particular, RAL. Naïve patients with CD4+ nadir <100 cells/μL were more likely to develop VF, particularly if they initiated RAL or EVG/c. In the ART switching population, initiation of RAL and EVG/c was associated with both VF and INSTI discontinuation. There were no differences in the time to VF and INSTI discontinuation between DTG, EVG/c and RAL. Immunological parameters improved in the three groups and for the three drugs assessed. Safety and tolerability were consistent with expected safety profiles.DiscussionWhereas second-generation INSTIs are preferred treatment options worldwide, and DTG is one of the treatment of choices in resource-limited settings, first-generation INSTIs may still provide high virological and immunological effectiveness when DTG is not available

Spatiotemporal Characteristics of the Largest HIV-1 CRF02_AG Outbreak in Spain: Evidence for Onward Transmissions

Background and Aim: The circulating recombinant form 02_AG (CRF02_AG) is the predominant clade among the human immunodeficiency virus type-1 (HIV-1) non-Bs with a prevalence of 5.97% (95% Confidence Interval-CI: 5.41–6.57%) across Spain. Our aim was to estimate the levels of regional clustering for CRF02_AG and the spatiotemporal characteristics of the largest CRF02_AG subepidemic in Spain.Methods: We studied 396 CRF02_AG sequences obtained from HIV-1 diagnosed patients during 2000–2014 from 10 autonomous communities of Spain. Phylogenetic analysis was performed on the 391 CRF02_AG sequences along with all globally sampled CRF02_AG sequences (N = 3,302) as references. Phylodynamic and phylogeographic analysis was performed to the largest CRF02_AG monophyletic cluster by a Bayesian method in BEAST v1.8.0 and by reconstructing ancestral states using the criterion of parsimony in Mesquite v3.4, respectively.Results: The HIV-1 CRF02_AG prevalence differed across Spanish autonomous communities we sampled from (p < 0.001). Phylogenetic analysis revealed that 52.7% of the CRF02_AG sequences formed 56 monophyletic clusters, with a range of 2–79 sequences. The CRF02_AG regional dispersal differed across Spain (p = 0.003), as suggested by monophyletic clustering. For the largest monophyletic cluster (subepidemic) (N = 79), 49.4% of the clustered sequences originated from Madrid, while most sequences (51.9%) had been obtained from men having sex with men (MSM). Molecular clock analysis suggested that the origin (tMRCA) of the CRF02_AG subepidemic was in 2002 (median estimate; 95% Highest Posterior Density-HPD interval: 1999–2004). Additionally, we found significant clustering within the CRF02_AG subepidemic according to the ethnic origin.Conclusion: CRF02_AG has been introduced as a result of multiple introductions in Spain, following regional dispersal in several cases. We showed that CRF02_AG transmissions were mostly due to regional dispersal in Spain. The hot-spot for the largest CRF02_AG regional subepidemic in Spain was in Madrid associated with MSM transmission risk group. The existence of subepidemics suggest that several spillovers occurred from Madrid to other areas. CRF02_AG sequences from Hispanics were clustered in a separate subclade suggesting no linkage between the local and Hispanic subepidemics

Análisis de las características clínicas, forma de presentación, abordaje terapéutico y pronóstico de los pacientes con diagnóstico de infarto de miocardio en la resonancia magnética y ausencia de lesiones significativas en la coronariografía

Introducción y objetivo: Entre el 5 al 10% de los pacientes con infarto de miocardio no presentan lesiones coronarias obstructivas. Hasta ahora, la mayoría de los estudios se han centrado en el síndrome coronario agudo, incluyendo diferentes entidades clínicas con una presentación similar englobadas bajo el término MINOCA (infarto de miocardio sin aterosclerosis coronaria obstructiva). El objetivo de este estudio fue evaluar el pronóstico de los pacientes con diagnóstico de infarto verdadero, confirmado por resonancia magnética cardíaca (RMC), en ausencia de lesiones coronarias significativas. Material y Métodos: Registro multicéntrico prospectivo, que incluye 120 pacientes consecutivos con infarto confirmado por RMC y sin lesiones coronarias obstructivas. Se analizaron los eventos cardiovasculares adversos (ECA: muerte, infarto no fatal, accidente cerebrovascular o reingreso por causa cardiaca); El seguimiento fue de tres años. Resultados: Setenta y seis pacientes (63,3%) ingresaron con diagnóstico de síndrome coronario agudo, y cuarenta y cuatro (36,6%) por otras causas (principalmente insuficiencia cardiaca); el diagnóstico definitivo se estableció por RMC. La mayoría de los pacientes (64,2%) eran hombres, la edad media fue de 58,83 ± 13,52 años. Los pacientes presentaban infartos de pequeño tamaño: 83 (69,1%) definidos como la presencia de realce tardío en uno o dos segmentos miocárdicos, principalmente eran infartos transmurales (en el 77,5% de los pacientes) y con fracción de eyección conservada (mediana 54,8%, IQ 37%-62%). La localización más frecuente del infarto fue la inferolateral (n = 38, 31,7%). Durante el seguimiento, 43 pacientes (35,8%) presentaron un evento cardiovascular mayor y 9 (7,5%) de ellos fallecieron. En el análisis multivariable, el presentar realce en 2 segmentos miocárdicos en la resonancia magnética cardiaca se asoció con un riesgo dos veces mayor de eventos cardíacos adversos en comparación con un segmento. Así mismo, la afectación de ¿3 segmentos miocárdicos casi triplica significativamente el riesgo de eventos cardiovasculares en el seguimiento (Hazard ratio [HR] 2,32, intervalo de confianza [IC] del 95 % 0,97¿5,83, p=0,058) (HR 2,71, IC del 95 % 1,04¿7,04, p= 0,040 respectivamente). Conclusiones: Los pacientes con verdaderos infartos sin lesiones coronarias significativas tuvieron predominantemente infartos pequeños tamaño. La afectación de 3 segmentos del miocardio se asocia con un riesgo significativamente mayor de eventos cardiovasculares adversos

Multiple intraventricular trombosis in trasient apical dyskinetic syndrome

A 71-year-old woman with no history of cardiovascular disease or risk factors presented to the emergency department for acute dyspnoea and chest pain after intense emotional stress. At initial evaluation, the blood pressure was 110/70 mmHg and physical examination showed third heart sound and pulmonary bilateral crepitation. The electrocardiogram demonstrated T-wave inversion on the inferior and anterior precordial leads (FIGURE A), accompanied with cardiac serum markers elevation (Troponin I 0,97 ng/dL). A chest x-ray revealed enlarged cardiac silhouette, pulmonary vascular congestion and slight pleural effusion. The patient was admitted to the cardiac care unit. Transthoracic echocardiography revealed akinesia of the left ventricular mid-apical segments with an ejection fraction of 35%, as well as few moveable masses affixed to left ventricular apex recesses compatible with intraventricular thrombi (FIGURE B-C-D-E). Antithrombotic therapy with low molecular weight heparin was started. She underwent a coronary angiography with no evidence of obstructive disease. Forty-eight hours after, a cardiac magnetic resonance was performed, showing apical myocardial inflammation (oedema), no late gadolinium enhancement and the disappearance of the ventricular thrombi. The patient was discharged with transient apical ballooning syndrome diagnosis (Tako-tsubo cardiomyopathy) under acenocumarol and betablocker treatment. Three months later, echocardiography control showed left ventricle contractile and systolic function recovery. Intraventricular thrombus formation in Tako-tsubo cardiomyopathy is an early and infrequent complication that may be detected in 2% to 8% of patients. It usually appears isolated, and in relation with the myocardial contractile dysfunction. Duration of antithrombotic therapy or its prophylaxis is not well established. It is frequently recommended three months of anticoagulation if intraventricular thrombus is detected. In the absence of ventricular thrombus but with severe left ventricular dysfunction, anticoagulation may be considered for three months or until dyskinesia has resolved. Mujer de 71 años sin antecedentes de riesgo cardiovascular acude al servicio de Urgencias por un episodio súbito de disnea intensa, y opresión precordial irradiada a hombro izquierdo, de varias horas de evolución tras una situación de estrés emocional. En la exploración física observamos cifras de TA:110/70mmHg una FC 90 lpm y crepitantes bibasales y 3º tono en la auscultación. El electrocardiograma de urgencias mostraba ondas T negativas en I, II, III, aVF, v3-v6, (PANEL A) acompañado de elevación de marcadores de daño miocárdico (CK 191 U/L; Troponina 0,97 ng/dL). Ante el diagnóstico de IAMSEST la paciente ingresa en la Unidad de cuidados intensivos. La coronariografía no mostró lesiones significativas. La ecocardiografía mostró disfunción sistólica con acinesia de toda la zona apical del v.izquierdo y presencia de varias masas bamboleantes de bordes nítidos (ancladas en los recesos de ápex y tercio distal de septo) compatible con trombos intraventriculares (PANELES B-C-D-E). Se inició tratamiento anticoagulante con HBPM. A las 48 horas se realizó una resonancia magnética cardiaca que mostró edema en ápex y ausencia de realce tardío con desaparición de los trombos. La paciente fue dada de alta con diagnóstico de Sd de takotsubo o discinesia apical transitoria  tratado con betabloqueantes y anticoagulantes orales. En el control ecocardiográfico realizado a los 3 meses se observó normalización de la función sistólica y de la contractilidad de los segmentos apicales. La trombosis intraventricular en el sd de Takotsubo es una complicación temprana e infrecuente en relación con la alteración de la contractilidad miocárdica (2-8% de los casos), aunque puede darse también taras recuperar la contractilidad.  La duración de su tratamiento así como su profilaxis no están claramente establecidas. Se recomienda en general, si existe trombo intraventricular, anticoagulación durante 3 meses. En ausencia de trombo, pero con disfunción severa del ventrículo izquierdo se debe valorar la posibilidad de anticoagular durante tres meses, o hasta que se recupere la función sistólica, eligiendo siempre la opción más corta

Prognostic utility of electrocardiograms in patients with hypertension older than 65 years. The PAFRES study

Objetivo La hipertrofia ventricular izquierda es el marcador de daño de órgano diana más frecuente en la hipertensión arterial. Habitualmente se realiza un ECG para su identificación. El objetivo de este trabajo es analizar la utilidad pronóstica de otras alteraciones electrocardiográficas en pacientes hipertensos, más allá de la hipertrofia ventricular. Materiales y métodos Se incluyeron 1.003 pacientes hipertensos mayores de 65 años. Se recogieron factores de riesgo, historia cardiovascular previa y tratamiento médico. Se analizaron diferentes alteraciones electrocardiográficas, incluyendo índice de Sokolow-Lyon, índice de Cornell, presencia de sobrecarga ventricular y bloqueos de rama, entre otros. Se llevó a cabo un seguimiento de 2 años con recogida de eventos cardiovasculares mayores (mortalidad, infarto de miocardio, accidentes cerebrovascular o ingreso por insuficiencia cardiaca). Resultados La edad media de la población era de 72,9 ± 5,8 años, con un 47,5% de varones. Durante el seguimiento el 13,9% sufrieron un evento cardiovascular mayor. Estos pacientes eran de mayor edad, más fumadores y practicaban menos ejercicio físico, sin presentar diferencias en el tratamiento antihipertensivo empleado ni en el control tensional. El patrón de sobrecarga ventricular (HR: 1,93; IC 95%: 1,160-3,196; p = 0,011) y el bloqueo completo de rama izquierda (HR: 2,27; IC 95%: 1,040-4,956; p = 0,040) se comportaron como factores electrocardiográficos predictores independientes de eventos cardiovasculares mayores, no así la hipertrofia ventricular izquierda por Sokolow y/o Cornell. Conclusiones En pacientes hipertensos, la existencia en el ECG basal de un bloqueo completo de rama izquierda o un patrón de sobrecarga ventricular identifica a una población de mayor riesgo cardiovascular.Objective Left ventricular hypertrophy is the most common marker of target organ damage in arterial hypertension. Electrocardiograms are typically performed to identify left ventricular hypertrophy. The aim of this study was to analyse the prognostic utility of other electrocardiographic abnormalities in patients with arterial hypertension, beyond ventricular hypertrophy. Materials and methods The study included 1003 patients older than 65 years with arterial hypertension. We recorded risk factors, previous cardiovascular history and medical treatment and analysed various electrocardiographic abnormalities including the Sokolow-Lyon index, the Cornell index, ventricular overload and branch blocks. The study conducted a 2-year follow-up, recording the major cardiovascular events (mortality, myocardial infarction, stroke and hospitalisation for heart failure). Results The study population's mean age was 72.9 ± 5.8 years, 47.5% of whom were men. During the follow-up, 13.9% of the patients experienced a major cardiovascular event. These patients were older, more often smokers and engaged in less physical exercise, without presenting differences in the antihypertensive therapy or blood pressure control. The ventricular overload pattern (HR: 1.93; 95% CI: 1.160-3.196; P = .011) and the complete left bundle branch block (HR: 2.27; 95% CI: 1.040-4.956; P = .040) behaved as independent electrocardiographic predictors of major cardiovascular events; however, left ventricular hypertrophy using the Sokolow and/or Cornell index did not behave as such. Conclusions For patients with hypertension, the presence in the baseline electrocardiogram of complete left bundle branch block or a pattern of ventricular overload identifies a population at increased cardiovascular risk

Prognosis impact of diabetes in elderly women and men with non-ST elevation acute coronary syndrome

Few studies have addressed to date the interaction between sex and diabetes mellitus (DM) in the prognosis of elderly patients with non-ST-segment elevation acute coronary syndrome (NSTEACS). Our aim was to address the role of DM in the prognosis of non-selected elderly patients with NSTEACS according to sex. A retrospective analysis from 11 Spanish NSTEACS registries was conducted, including patients aged ≥70 years. The primary end point was one-year all-cause mortality. A total of 7211 patients were included, 2,770 (38.4%) were women, and 39.9% had DM. Compared with the men, the women were older (79.95 ± 5.75 vs. 78.45 ± 5.43 years, p < 0.001) and more often had a history of hypertension (77% vs. 83.1%, p < 0.01). Anemia and chronic kidney disease were both more common in women. On the other hand, they less frequently had a prior history of arteriosclerotic cardiovascular disease or comorbidities such as peripheral artery disease and chronic pulmonary disease. Women showed a worse clinical profile on admission, though an invasive approach and in-hospital revascularization were both more often performed in men (p < 0.001). At a one-year follow-up, 1090 patients (15%) had died, without a difference between sexes. Male sex was an independent predictor of mortality (HR = 1.15, 95% CI 1.01 to 1.32, p = 0.035), and there was a significant interaction between sex and DM (p = 0.002). DM was strongly associated with mortality in women (HR: 1.45, 95% CI = 1.18-1.78; p < 0.001), but not in men (HR: 0.98, 95% CI = 0.84-1.14; p = 0.787). In conclusion, DM is associated with mortality in older women with NSTEACS, but not in men

Conservatively managed patients with non-ST-segment elevation acute coronary syndrome are undertreated with indicated medicines.

Introduction and aimsPatients with non-ST-elevation acute coronary syndrome (NSTE-ACS) are often managed conservatively. Clinical practice guidelines recommend treating these patients with the same pharmacological drugs as those who receive invasive treatment. We analyze the use of new antiplatelet drugs (NADs) and other recommended treatments in people discharged following an NSTE-ACS according to the treatment strategy used, comparing the medium-term prognosis between groups.MethodsProspective observational multicenter registry study in 1717 patients discharged from hospital following an ACS; 1143 patients had experienced an NSTE-ACS. We analyzed groups receiving the following treatment: No cardiac catheterization (NO CATH): n = 134; 11.7%; Cardiac catheterization without revascularization (CATH-NO REVASC): n = 256; 22.4%; percutaneous coronary intervention (PCI): n = 629; 55.0%; and coronary artery bypass graft (CABG): n = 124; 10.8%. We assessed major adverse cardiovascular events (MACE), all-cause mortality, and hemorrhagic complications at one year.ResultsNO CATH was the oldest, had the most comorbidities, and was at the highest risk for ischemic and hemorrhagic events. Few patients who were not revascularized with PCI received NADs (NO CATH: 3.7%; CATH-NO REVASC: 10.6%; PCI: 43.2%; CABG: 3.2%; pConclusionsDespite current invasive management of NSTE-ACS, patients not receiving catheterization are at very high risk for under treatment with recommended drugs, including NADs. Their medium-term prognosis is poor, with high mortality. Patients treated with PCI receive better pharmacological management, with high use of NADs

Influencia de las comorbilidades en la decisión del tratamiento invasivo en ancianos con SCASEST

Introduction and objectives: The presence of comorbidities in elderly patients with non-ST-segment elevation acute coronary syndrome worsens its prognosis. The objective of the study was to analyze the impact of the burden of comorbidities in the decision of using invasive management in these patients. Methods: A total of 7211 patients > 70 years old from 11 Spanish registries were included. Individual data were analyzed in a common database. We assessed the presence of 6 comorbidities and their association with coronary angiography during admission. Results: The mean age was 79 ± 6 years and the mean CRACE score was 150 ± 21 points. A total of 1179 patients (16%) were treated conservatively. The presence of each comorbidity was associated with less invasive management (adjusted for predictive clinical variables): cerebrovascular disease (OR, 0.78; 95%CI, 0.64-0.95; P = .01), anemia (OR, 0.64; 95%CI, 0.54-0.76; P < .0001), chronic kidney disease (OR, 0.65; 95%CI, 0.56-0.75; P < .0001), peripheral arterial disease (OR, 0.79; 95%CI, 0.65-0.96; P = .02), chronic lung disease (OR, 0.85; IC95%, 0.71-0.99; P = .05), and diabetes mellitus (OR, 0.85; 95%CI, 0.74-0.98; P < .03). The increase in the number of comorbidities (comorbidity burden) was associated with a reduction in coronary angiographies GRACE score: 1 comorbidity (OR, 0.66; 95%CI, 0.54-0.81), 2 comorbidities (OR, 0.55; 95%CI, 0.45-0.69), 3 comorbidities (OR, 0.37; 95%CI, 0.29-0.47), 4 comorbidities (OR, 0.33; 95%CI, 0.24-0.45), ≥ 5 comorbidities (OR, 0.21; 95%CI, 0.12-0.36); all P values < .0001 compared to 0. Conclusions: The number of coronary angiographies performed drops as the number of comorbidities increases in elderly patients with non-ST-segment elevation acute coronary syndrome. More studies are still needed to know what the best management of these patients should be.Introducción y objetivos: La comorbilidad en ancianos con síndrome coronario agudo sin elevación del segmento ST empeora el pronóstico. El objetivo fue analizar la influencia de la carga de comorbilidad en la decisión del tratamiento invasivo en ancianos con SCASEST. Métodos: Se incluyeron 7.211 pacientes mayores de 70 años procedentes de 11 registros españoles. Los datos se analizaron en una base de datos conjunta. Se evaluó la presencia de 6 enfermedades simultáneas y su asociación con la realización de coronariografía durante el ingreso. Resultados: La edad media fue de 79 ± 6 años y la puntuación GRACE media fue de 150 ± 21 puntos. Fueron tratados de manera conservadora 1.179 pacientes (16%). La presencia de cada enfermedad se asoció con un menor abordaje invasivo (ajustado por variables clínicas predictivas): enfermedad cerebrovascular (odds ratio [OR] = 0,78; intervalo de confianza del 95% [IC95%], 0,64-0,95; p = 0,01), anemia (OR = 0,64; IC95%, 0,54-0,76; p < 0,0001), insuficiencia renal (OR = 0,65; IC95%, 0,56-0,75; p < 0,0001), arteriopatía periférica (OR = 0,79; IC95%, 0,65-0,96; p = 0,02), enfermedad pulmonar crónica (OR = 0,85; IC95%, 0,71-0,99; p = 0,05) y diabetes mellitus (OR = 0,85; IC95%, 0,74-0,98; p = 0,03). Asimismo, el aumento del número de enfermedades (carga de comorbilidad) se asoció con menor realización de coronariografías, ajustado por la escala GRACE: 1 enfermedad (OR = 0,66; IC95%, 0,54-0,81); 2 (OR = 0,55; IC95%, 0,45-0,69); 3 (OR = 0,37; IC95%, 0,29-0,47); 4 (OR = 0,33; IC95%, 0,24-0,45); ≥ 5 (OR = 0,21; IC95%, 0,12-0,36); todos p < 0,0001, en comparación con ninguna enfermedad. Conclusiones: Conforme aumenta la comorbilidad disminuye la realización de coronariografías en ancianos con síndrome coronario agudo sin elevación del segmento ST. Se necesitan estudios que investiguen la mejor estrategia diagnóstico-terapéutica en estos pacientes