Particle size and cholesterol content of circulating HDL correlate with cardiovascular death in chronic heart failure

Evidence regarding any association of HDL-particle (HDL-P) derangements and HDL-cholesterol content with cardiovascular (CV) death in chronic heart failure (HF) is lacking. To investigate the prognostic value of HDL-P size (HDL-Sz) and the number of cholesterol molecules per HDL-P for CV death in HF patients. Outpatient chronic HF patients were enrolled. Baseline HDL-P number, subfractions and HDL-Sz were measured using 1H-NMR spectroscopy. The HDL-C/P ratio was calculated as HDL-cholesterol over HDL-P. Endpoint was CV death, with non-CV death as the competing event. 422 patients were included and followed-up during a median of 4.1 (0–8) years. CV death occurred in 120 (30.5%) patients. Mean HDL-Sz was higher in CV dead as compared with survivors (8.39 nm vs. 8.31 nm, p < 0.001). This change in size was due to a reduction in the percentage of small HDL-P (54.6% vs. 60% for CV-death vs. alive; p < 0.001). HDL-C/P ratio was higher in the CV-death group (51.0 vs. 48.3, p < 0.001). HDL-Sz and HDL-C/P ratio were significantly associated with CV death after multivariable regression analysis (HR 1.22 [95% CI 1.01–1.47], p = 0.041 and HR 1.04 [95% CI 1.01–1.07], p = 0.008 respectively). HDL-Sz and HDL-C/P ratio are independent predictors of CV death in chronic HF patients.Tis work was supported by Grants from Fundació La MARATÓ de TV3 (201502 and 201516 to AB-G, 201602- 30-31 to NA and JJ), Ministerio de Educación y Ciencia (SAF2014-59892 to AB-G), AdvanceCat (2014-2020 to AB-G), Ministerio de Economía y Competitividad (MINECO)—Instituto de Salud Carlos III (ISCIII) (PI17- 00232 to JJ, PI17-01362 to NA, PI15-00625 to DM, and RED2018-102799-T to JJ), and by CIBER on Cardiovascular Diseases (CIBERCV, CB16/11/00403) and CIBER for Diabetes and Associated Metabolic Diseases (CIBERDEM, CB15/00071 and CB07/08/0016) are an initiative from ISCIII, Spain with co-funding from the European Regional Development Fund (ERDF). JJ is supported by funds provided by ISCIII (Grant CPII18/00004, Miguel Servet II program)

Particle size and cholesterol content of circulating HDL correlate with cardiovascular death in chronic heart failure

Altres ajuts: Fundació la Marató de TV3: 201602-30-31; 201502Evidence regarding any association of HDL-particle (HDL-P) derangements and HDL-cholesterol content with cardiovascular (CV) death in chronic heart failure (HF) is lacking. To investigate the prognostic value of HDL-P size (HDL-Sz) and the number of cholesterol molecules per HDL-P for CV death in HF patients. Outpatient chronic HF patients were enrolled. Baseline HDL-P number, subfractions and HDL-Sz were measured using 1H-NMR spectroscopy. The HDL-C/P ratio was calculated as HDL-cholesterol over HDL-P. Endpoint was CV death, with non-CV death as the competing event. 422 patients were included and followed-up during a median of 4.1 (0-8) years. CV death occurred in 120 (30.5%) patients. Mean HDL-Sz was higher in CV dead as compared with survivors (8.39 nm vs. 8.31 nm, p < 0.001). This change in size was due to a reduction in the percentage of small HDL-P (54.6% vs. 60% for CV-death vs. alive; p < 0.001). HDL-C/P ratio was higher in the CV-death group (51.0 vs. 48.3, p < 0.001). HDL-Sz and HDL-C/P ratio were significantly associated with CV death after multivariable regression analysis (HR 1.22 [95% CI 1.01-1.47], p = 0.041 and HR 1.04 [95% CI 1.01-1.07], p = 0.008 respectively). HDL-Sz and HDL-C/P ratio are independent predictors of CV death in chronic HF patients

Prognosis of Paradoxical Low-Flow Low-Gradient Aortic Stenosis: A Severe, Non-critical Form, With Surgical Treatment Benefits

Aortic stenosis; Echocardiography; Heart valve diseaseEstenosis aórtica; Ecocardiografía; Enfermedad de las válvulas del corazónEstenosi aòrtica; Ecocardiografia; Malaltia de les vàlvules cardíaquesObjectives: To determine the risk of mortality and need for aortic valve replacement (AVR) in patients with low-flow low-gradient (LFLG) aortic stenosis (AS). Methods: A longitudinal multicentre study including consecutive patients with severe AS (aortic valve area [AVA] 35 ml/m2) and LFLG (mean gradient < 40 mmHg, SVi ≤ 35 ml/m2). Results: Of 1,391 patients, 147 (10.5%) had LFLG, 752 (54.1%) HG, and 492 (35.4%) NFLG. Echocardiographic parameters of the LFLG group showed similar AVA to the HG group but with less severity in the dimensionless index, calcification, and hypertrophy. The HG group required AVR earlier than NFLG (p < 0.001) and LFLG (p < 0.001), with no differences between LFLG and NFLG groups (p = 0.358). Overall mortality was 27.7% (CI 95% 25.3–30.1) with no differences among groups (p = 0.319). The impact of AVR in terms of overall mortality reduction was observed the most in patients with HG (hazard ratio [HR]: 0.17; 95% CI: 0.12–0.23; p < 0.001), followed by patients with LFLG (HR: 0.25; 95% CI: 0.13–0.49; p < 0.001), and finally patients with NFLG (HR: 0.29; 95% CI: 0.20–0.44; p < 0.001), with a risk reduction of 84, 75, and 71%, respectively. Conclusions: Paradoxical LFLG AS affects 10.5% of severe AS, and has a lower need for AVR than the HG group and similar to the NFLG group, with no differences in mortality. AVR had a lower impact on LFLG AS compared with HG AS. Therefore, the findings of the present study showed LFLG AS to have an intermediate clinical risk profile between the HG and NFHG groups.AGu has received funding from the Spanish Ministry of Science, Innovation and Universities (IJC2018- 037349-I)

Long-term antibiotic therapy in patients with surgery-indicated not undergoing surgery infective endocarditis

Background: To date, there is little information regarding management of patients with infective endocarditis (IE) that did not undergo an indicated surgery. Therefore, we aimed to evaluate prognosis of these patients treated with a long-term antibiotic treatment strategy, including oral long term suppressive antibiotic treatment in five referral centres with a multidisciplinary endocarditis team.Methods: This retrospective, multicenter study retrieved individual patient-level data from five referral centres in Spain. Among a total of 1797, 32 consecutive patients with IE were examined (median age 72 years; 78% males) who had not undergone an indicated surgery, but received long-term antibiotic treatment (LTAT) and were followed by a multidisciplinary endocarditis team, between 2011 and 2019. Primary outcomes were infection relapse and mortality during follow-up.Results: Among 32 patients, 21 had IE associated with prostheses. Of the latter, 8 had an ascending aorta prosthetic graft. In 24 patients, a switch to long-term oral suppressive antibiotic treatment (LOSAT) was considered. The median duration of LOSAT was 277 days. Four patients experienced a relapse during follow-up. One patient died within 60 days, and 12 patients died between 60 days and 3 years. However, only 4 deaths were related to IE.Conclusions: The present study results suggest that a LTAT strategy, including LOSAT, might be considered for patients with IE that cannot undergo an indicated surgery. After hospitalization, they should be followed by a multidisciplinary endocarditis team

Factors predictius d’esdeveniments en pacients amb estenosi valvular aòrtica severa asimptomàtica

L’Estenosi aòrtica (EAo) és la valvulopatia més comuna i que requereix amb més freqüència substitució valvular aòrtica (SVAo) en els països desenvolupats. La substitució valvular tant sigui per tècniques quirúrgiques com percutànies és l’únic tractament eficaç i aquest tractament està indicat quan hi ha símptomes associats o disfunció ventricular esquerra. En els últims anys, els bons resultats de la cirurgia cardíaca així com els significatius avenços de les tècniques percutànies han fet que ens plantegem el recanvi valvular aòrtic en fases més precoces de la malaltia, quan el pacient encara està asimptomàtic. Tot i això, la decisió entre realitzar una cirurgia precoç versus l’estratègia d’observar i detectar factors predictius d’esdeveniments (coneguda com “watchful waiting strategy”) és una decisió complexa que engloba una valoració global del pacient i continua essent un tema no resolt. Idealment, la intervenció s’ha de realitzar just quan el ventricle esquerre inicia un cert grau de disfunció però abans que aparegui un dany irreversible. La integració de la clínica, l’educació sanitària, l’estratificació del risc quirúrgic, l’anàlisi de l’ecocardiografia i altres tècniques d’imatge, la valoració dels biomarcadors i l’evolució dels mateixos en el temps, així com la realització i correcte interpretació de l’ecocardiografia d’esforç físic són punts bàsics que s’han d’incloure en una programa de maneig de pacients amb estenosi aòrtica severa asimptomàtica en Unitats clíniques especialitzades en malalties valvulars, per tal de realitzar una indicació de recanvi valvular en el moment més oportú pel pacient, així com establir la indicació de la millor tècnica i abordatge per tal de portar a terme el recanvi valvular. En aquesta tesi doctoral s’ha realitzat un estudi prospectiu dels pacients amb EAo severa asimptomàtica atesos en una consulta monogràfica de pacients valvulars de l’Hospital Germans Trias i Pujol amb la finalitat de conèixer les característiques i l’evolució d’aquests pacients en el nostre mitjà i analitzar els diferents factors predictius d’esdeveniments en pacients amb EAo severa asimptomàtica. Hem realitzat un estudi i un seguiment protocol&#8226;litzat dels pacients, que ens ha permès obtenir informació de les característiques clíniques d’aquests pacients, de la seva evolució i del seu pronòstic. Així mateix, hem pogut analitzar l’aportació de les diferents tècniques diagnòstiques utilitzades. Així, hem observat com l’ecocardiografia d’esforç és una tècnica que ens ajuda en el maneig dels pacients no tan sols si es realitza en la valoració inicial d’aquests pacients, sinó també quan es repeteix l’estudi al llarg del seguiment. D’altra banda, un enfocament biològic amb l’ús de biomarcadors cardíacs ens ha permès detectar pacients de risc de descompensació, fet que ajuda a un millor maneig dels pacients amb EAo severa asimptomàtica. En la nostre sèrie de pacients amb EAo severa asimptomàtica no només el valor inicial de Troponina T d’ alta sensibilitat (Hs-TnT) comporta un major risc d’esdeveniment a l’any de seguiment sinó que un increment >20% del valor de Hs-TnT als 6 mesos, multiplica per 8 el risc d’esdeveniment a l’any de seguiment, independentment del valor obtingut en l’analítica inicial. Amb la mateixa idea, hem iniciat un estudi que posa els fonaments per seguir una línia d’investigació de l’aportació de la proteòmica en el maneig d’ aquests pacients. Tota l’experiència i informació obtinguda ens permetrà determinar millor el moment per indicar el recanvi valvular dels nostres pacients abans que apareguin canvis irreversibles del ventricle esquerre.La Estenosis aórtica (EAO) es la valvulopatía más común y que requiere con más frecuencia sustitución valvular aórtica (SVAo) en los países desarrollados. La sustitución valvular tanto sea por técnicas quirúrgicas como percutáneas es el único tratamiento eficaz y este tratamiento está indicado cuando hay síntomas asociados o disfunción ventricular izquierda. En los últimos años, los buenos resultados de la cirugía cardíaca así como los significativos avances en las técnicas percutáneas han hecho que nos planteemos el recambio valvular aórtico en fases más precoces de la enfermedad, cuando el paciente aún está asintomático. Sin embargo, la decisión entre realizar una cirugía precoz versus la estrategia de observar y detectar factores predictivos de eventos (conocida como “watchful waiting strategy”) es una decisión compleja que engloba una valoración global del paciente y sigue siendo un tema no resuelto. Idealmente, la intervención se debe realizar justo cuando el ventrículo izquierdo inicia un cierto grado de disfunción pero antes de que aparezca un daño irreversible. La integración de la clínica, la educación sanitaria, la estratificación del riesgo quirúrgico, el análisis de la ecocardiografía y otras técnicas de imagen, la valoración de los biomarcadores y la evolución de los mismos en el tiempo, así como la realización y correcto interpretación de la ecocardiografía de esfuerzo físico son puntos básicos que deben incluirse en una programa de manejo de pacientes con estenosis aórtica severa asintomática en Unidades Clínicas especializadas en Enfermedades Valvulares, para realizar una indicación de recambio valvular en el momento más oportuno para el paciente, así como establecer la indicación de la mejor técnica y abordaje para llevar a cabo el recambio valvular. En esta tesis doctoral se ha realizado un estudio prospectivo de los pacientes con EAO severa asintomática atendidos en una consulta monográfica de pacientes valvulares del Hospital Germans Trias i Pujol con el fin de conocer las características y la evolución de estos pacientes en el nuestro medio y analizar los diferentes factores predictivos de eventos en pacientes con EAO severa asintomática. Hemos realizado un estudio y un seguimiento protocolizado de los pacientes, que nos ha permitido obtener información de las características clínicas de dichos pacientes, de su evolución y de su pronóstico. Asimismo, hemos podido analizar la aportación de las diferentes técnicas diagnósticas utilizadas. Así, hemos observado como la ecocardiografía de esfuerzo es una técnica que nos ayuda en el manejo de los pacientes no sólo si se realiza en la valoración inicial de estos pacientes, sino también cuando se repite el estudio a lo largo del seguimiento. Por otra parte, un enfoque biológico con el uso de biomarcadores cardíacos nos ha permitido detectar pacientes de riesgo de descompensación, lo que ayuda a un mejor manejo de los pacientes con EAO severa asintomática. En nuestra serie de pacientes con EAO severa asintomática no sólo el valor inicial de Troponina T de alta sensibilidad (Hs-TNT) conlleva un mayor riesgo de evento al año de seguimiento sino que un incremento> 20% del valor de Hs-TNT a los 6 meses, multiplica por 8 el riesgo de evento al año de seguimiento, independientemente del valor obtenido en la analítica inicial. Con la misma idea, hemos iniciado un estudio que pone los cimientos para seguir una línea de investigación de la aportación de la proteómica en el manejo de estos pacientes. Toda la experiencia e información obtenida nos permitirá determinar mejor el momento para indicar el recambio valvular de nuestros pacientes antes de que aparezcan cambios irreversibles del ventrículo izquierdo.Aortic stenosis (AoS) is the most frequent valve pathology in the developed world and the one that most frequently requires aortic valve replacement (AoVR). Valve replacement, either surgical or percutaneous, is the only effective treatment and is indicated in the presence of associated symptoms or left ventricular dysfunction. In the last years, the good results achieved in heart surgery and the significant advances made in percutaneous techniques have allowed aortic valve replacement to be considered at an earlier stage of the disease, when the patient still has no symptoms. However, early surgery vs. event predictive factor observation and detection (the “watchful waiting” strategy) is a complex decision requiring global patient assessment, and it remains unresolved. Ideally, the surgical procedure should be carried out as soon as the left ventricle begins to present a certain degree of dysfunction, before irreversible damage occurs. Clinical data integration, healthcare education, surgical risk stratification, echocardiography evaluation and analysis of other imaging techniques, biomarker assessment and biomarker evolution with time, and a correct interpretation of physical activity echocardiography are key points to be included in asymptomatic severe aortic stenosis patient management programs in clinical facilities specialized in valve pathologies. This allows valve replacement to be indicated in the most timely fashion possible for the patient, as well as the best technique and approach for valve replacement purposes to be established. As part of this PhD thesis, a prospective study of asymptomatic severe AoS patients from a specialized valve patient consultation at Germans Trias i Pujol Hospital was carried out. The objective was to analyze the characteristics and evolution of these patients in our environment and assess event predictive factors in asymptomatic severe AoS patients. A protocolized patient study and follow-up was performed, which provided significant information on patients&#8217; clinical characteristics, evolution, and prognosis. In addition, the contribution of the various diagnostic techniques used was also analyzed. Physical activity echocardiography proved to be helpful in terms of patient management, not only if carried out at baseline assessment, but also when repeated throughout follow-up. Moreover, a biological approach with the use of cardiac markers allowed decompensation risk patients to be detected, which translated into better asymptomatic severe AoS patient management. In our series of asymptomatic severe AoS patients, not only did high-sensitivity troponin T (Hs-TNT) baseline levels lead to a higher event risk after one-year follow-up, but also >20% increases in Hs-TNT levels after six months multiplied event risk after one-year follow-up by 8, regardless of baseline levels. With the same idea in mind, another study was set up in order to lay the foundations of a new research line on proteomics contribution in the management of these patients. The experience and information gathered will allow the best time for valve replacement indication to be determined before left ventricular irreversible changes occur.Universitat Autònoma de Barcelona. Programa de Doctorat en Medicin

Dynamic trajectories of left ventricular ejection fraction in heart failure

Background Long-term trajectories of left ventricular ejection fraction (LVEF) in heart failure (HF) are incompletely characterized. Objectives This study sought to examine LVEF trajectories in HF with reduced LVEF (<40%) and mid-range LVEF (40% to 49%) and the prognostic impact of LVEF dynamic changes over 15-year follow-up. Methods In this prospective, consecutive, observational registry of real-life HF outpatients, the authors performed 2-dimensional echocardiography at baseline and on a structured schedule after 1 year and then every 2 years up to 15 years. Results The mean number of LVEF measurements in the 1,160 included patients was 3.6 ± 1.7. As a whole, Loess curves of long-term LVEF trajectories showed an inverted U shape with a marked rise in LVEF during the first year, maintained up to a decade, and a slow LVEF decline thereafter (p for trajectory <0.001). This pattern was more pronounced in HF of nonischemic origin and in women. Patients with new-onset HF (=12 months) had a higher early increase in LVEF, whereas patients with ischemic HF showed a lower LVEF increase at 1 year; both groups had a relative plateau thereafter. Patients with HF with mid-range LVEF had less of an increase (3 ± 9%) than those with HF with reduced LVEF (9 ± 12%) during the first year (p < 0.001), but the groups overlapped after 15 years. Patients who died had lower final LVEF and worse LVEF dynamics in the immediately preceding period than survivors. Conclusions LVEF trajectories vary in HF depending on a number of disease modifiers, but an inverted U-shaped pattern with lower LVEF at both ends of the distribution emerged. A declining LVEF in the preceding period was associated with higher mortality.Peer ReviewedPostprint (author's final draft

Changes in echocardiographic parameters over time in paradoxical low-flow low-gradient aortic stenosis

Aims: To assess the progression of the disease and evolution of the main echocardiographic variables for quantifying AS in patients with severe low-flow low-gradient (LFLG) AS compared to other severe AS subtypes. Methods and results: Longitudinal, observational, multicenter study including consecutive asymptomatic patients with severe AS (aortic valve area, AVA 35mL/m2), or LFLG (mean gradient < 40 mmHg, SVi ≤ 35 mL/m²). AS progression was analyzed by comparing patients' baseline measurements and their last follow-up measurements or those taken prior to aortic valve replacement (AVR). Of the 903 included patients, 401 (44.4%) were HG, 405 (44.9%) NFLG, and 97 (10.7%) LFLG. Progression of the mean gradient in a linear mixed regression model was greater in low-gradient groups: LFLG vs. HG (regression coefficient 0.124, P = 0.005) and NFLG vs. HG (regression coefficient 0.068, P = 0.018). No differences were observed between the LFLG and NFLG groups (regression coefficient 0.056, P = 0.195). However, AVA reduction was slower in the LFLG group compared to the NFLG (P < 0.001). During follow-up, in conservatively-managed patients, 19.1% (n = 9) of LFLG patients evolved to having NFLG AS and 44.7% (n = 21) to having HG AS. In patients undergoing AVR, 58.0% (n = 29) of LFLG baseline patients received AVR with a HG AS. Conclusion: LFLG AS shows an intermediate AVA and gradient progression compared to NFLG and HG AS. The majority of patients initially classified as having LFLG AS changed over time to having other severe forms of AS, and most of them received AVR with a HG AS.Sin financiación6.300 Q1 JCR 20222.255 Q1 SJR 2022No data IDR 2022UE