Mar Domingo - Profile on Academia.edu (original) (raw)

Papers by Mar Domingo

Frontiers in Cardiovascular Medicine, Jan 5, 2021

Important differences in comorbidities and clinical characteristics exist between women and men w... more Important differences in comorbidities and clinical characteristics exist between women and men with heart failure (HF). In particular, differences in the kinetics of biological circulating biomarkers-a critical component of cardiovascular care-are highly relevant. Most circulating HF biomarkers are assessed daily by clinicians without taking sex into account, despite the multiple gender-related differences observed in plasma concentrations. Even in health, compared to men, women tend to exhibit higher levels of natriuretic peptides and galectin-3 and lower levels of cardiac troponins and the cardiac stress marker, soluble ST2. Many biological factors can provide a reliable explanation for these differences, like body composition, fat distribution, or menopausal status. Notwithstanding, these sex-specific differences in biomarker levels do not reflect different pathobiological mechanisms in HF between women and men, and they do not necessarily imply a need to use different diagnostic cut-off levels in clinical practice. To date, the sex-specific prognostic value of HF biomarkers for risk stratification is an unresolved issue that future research must elucidate. This review outlines current evidence regarding gender-related differences in circulating biomarkers widely used in HF, the pathophysiological mechanisms underlying these differences, and their clinical relevance.

European Heart Journal, Oct 1, 2022

Cardiac failure review, Jun 23, 2022

Heart failure with preserved ejection fraction (HFpEF) is a heterogeneous disorder developing fro... more Heart failure with preserved ejection fraction (HFpEF) is a heterogeneous disorder developing from multiple aetiologies with overlapping pathophysiological mechanisms. HFpEF diagnosis may be challenging, as neither cardiac imaging nor physical examination are sensitive in this situation. Here, we review biomarkers of HFpEF, of which the best supported are related to myocardial stretch and injury, including natriuretic peptides and cardiac troponins. An overview of biomarkers of inflammation, extracellular matrix derangements and fibrosis, senescence, vascular dysfunction, anaemia/iron deficiency and obesity is also provided. Finally, novel biomarkers from -omics technologies, including plasma metabolites and circulating microRNAs, are outlined briefly. A cardiac-centred approach to HFpEF diagnosis using natriuretic peptides seems reasonable at present in clinical practice. A holistic approach including biomarkers that provide information on the non-cardiac components of the HFpEF syndrome may enrich our understanding of the disease and may be useful in classifying HFpEF phenotypes or endotypes that may guide patient selection in HFpEF trials.

Journal of Clinical Medicine, Jan 31, 2022

We assessed differences in long-term all-cause and cardiovascular (CV) mortality in heart failure... more We assessed differences in long-term all-cause and cardiovascular (CV) mortality in heart failure (HF) outpatients based on the etiology of HF. Consecutive patients admitted to the HF Clinic from August 2001 to September 2019 (N = 2587) were considered for inclusion. HF etiology was divided into ischemic heart disease (IHD), dilated cardiomyopathy (DCM), hypertensive heart disease, alcoholic cardiomyopathy, drug-induced cardiomyopathy (DICM), valvular heart disease, and hypertrophic cardiomyopathy. All-cause death and CV death were the primary end points. Among 2387 patients included in the analysis (mean age 66.5 ± 12.5 years, 71.3% men), 1317 deaths were recorded (731 from CV cause) over a maximum follow-up of 18 years (median 4.1 years, interquartile range (IQR) 2-7.8). Considering IHD as the reference, only DCM had a lower risk of all-cause death (adjusted hazard ratio (aHR) 0.68, 95% confidence interval (CI) 0.56-0.83, p < 0.001), and only DICM had a higher risk of all-cause death (aHR 1.47, 95% CI 1.02-2.11, p = 0.04). However, almost all etiologies had a significantly lower risk of CV death than IHD. Among the studied HF etiologies, DCM and DICM have the lowest and highest risk of all-cause death, respectively, whereas IHD has the highest adjusted risk of CV death.

Circulation-heart Failure, Mar 1, 2019

BACKGROUND: Long-term trajectories of left ventricular ejection fraction (LVEF) in heart failure ... more BACKGROUND: Long-term trajectories of left ventricular ejection fraction (LVEF) in heart failure (HF) patients with preserved EF (HFpEF) remain unclear. Our objective was to assess long-term longitudinal trajectories in consecutive HFpEF patients and the prognostic impact of LVEF dynamic changes over time. Consecutive ambulatory HFpEF patients admitted to a multidisciplinary HF Unit were prospectively evaluated by 2-dimensional echocardiography at baseline and at 1, 3, 5, 7, 9, and 11 years of follow-up. Exclusion criteria were patients having a previous known LVEF <50%, patients undergoing only 1 echocardiogram study, and those with a diagnosis of dilated, noncompaction, alcoholic, or toxic cardiomyopathy. One hundred twenty-six patients (age, 71±13 years; 63% women) were included. The main pathogeneses were valvular disease (36%) and hypertension (28%). Atrial fibrillation was present in 67 patients (53%). The mean number of echocardiographies performed was 3±1.2 per patient. Locally weighted error sum of squares curves showed a smooth decrease of LVEF during the 11-year follow-up that was statistically significant in linear mixed-effects modeling (P=0.01). Ischemic patients showed a higher decrease than nonischemics. The great majority (88.9%) of patients remained in the HFpEF category during follow-up; 9.5% evolved toward HF with midrange LVEF, and only 1.6% dropped to HF with reduced LVEF. No significant relationship was found between LVEF dynamics in the immediate preceding period and mortality. CONCLUSIONS: LVEF remained ≥50% in the majority of patients with HFpEF for ≤11 years. Only 1.6% of patients evolved to HF with reduced LVEF. Dynamic LVEF changes were not associated with mortality.

European Heart Journal, Aug 2, 2013

Cardiovascular Diabetology, Mar 23, 2020

Background: Left ventricular ejection fraction (LVEF) trajectories and functional recovery with c... more Background: Left ventricular ejection fraction (LVEF) trajectories and functional recovery with current heart failure (HF) management is increasingly recognized. Type 2 diabetes mellitus (T2D) leads to a worse prognosis in HF patients. However, it is unknown whether T2D interferes with LVEF trajectories. The aim of this study was to prospectively assess very long-term (up to 15 years) LVEF trajectories in patients with and without T2D and underlying HF. Methods: Ambulatory patients admitted to a multidisciplinary HF clinic were prospectively evaluated by scheduled two-dimensional echocardiography at baseline, 1 year, and then every 2 years afterwards, up to 15 years. Statistical analyses of LVEF change with time were performed using the linear mixed effects (LME) models, and locally weighted error sum of squares (Loess) curves were plotted. Results: Of the 1921 patients, 461 diabetic and 699 non-diabetic patients with LVEF < 50% were included in the study. The mean number of echocardiography measurements performed in diabetic patients was 3.3 ± 1.6. Early LVEF recovery was similar in diabetic and non-diabetic patients, but Loess curves showed a more pronounced inverted U shape in diabetics with a more pronounced decline after 9 years. LME analysis showed a statistical interaction between T2D and LVEF trajectory over time (p = 0.009), which was statistically significant in patients with ischemic etiologies (p < 0.001). Other variables that showed an interaction between LVEF trajectories and T2D were male sex (p = 0.04) and HF duration (p = 0.008). Conclusions: LVEF trajectories in T2D patients with depressed systolic function showed a pronounced inverted U shape with a marked decline after 9 years. Diabetic cardiomyopathy may underlie the functional decline observed.

Evolocumab has no effects on heart failure with reduced ejection fraction injury biomarkers: The EVO‐HF trial

European Journal of Heart Failure

AimPatients with heart failure with reduced ejection fraction (HFrEF) have not been shown to bene... more AimPatients with heart failure with reduced ejection fraction (HFrEF) have not been shown to benefit from statins. We hypothesized that, by limiting disease progression in stable HFrEF of ischaemic etiology, the proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor evolocumab could reduce circulating troponin levels, a surrogate biomarker of myocyte injury and atherosclerosis progression.Methods and resultsThe EVO‐HF multicentre prospective randomized trial compared evolocumab (420 mg/month administered subcutaneously) plus guideline‐directed medical therapy (GDMT; n = 17) versus GDMT alone (n = 22) for 1 year in patients with stable coronary artery disease and left ventricular ejection fraction (LVEF) <40%, ischaemic aetiology, New York Heart Association class II, N‐terminal pro‐B‐type natriuretic peptide (NT‐proBNP) ≥400 pg/ml, high‐sensitivity troponin T (hs‐TnT) >10 pg/ml, low‐density lipoprotein cholesterol (LDL‐C) ≥70 mg/dl. The primary endpoint was change in h...

How mortality risk estimated by MAGGIC-HF, SHFM and BCN-Bio HF scores is modified after 12-month management in a multidisciplinary HF Clinic

European Heart Journal, 2020

Heart failure (HF) contemporary management has significantly improved over the past two decades l... more Heart failure (HF) contemporary management has significantly improved over the past two decades leading to better survival. How application of the contemporary HF management guidelines affects the risk of death estimated by available web-based risk scores is not elucidated. To assess changes in mortality risk prediction after a after a 12-month management period in a multidisciplinary HF Clinic. Out of 1,689 consecutive patients with HF admitted at our ambulatory HF Clinic from May 2006 to November 2018, those who completed one year follow-up were considered for the study. Patients without NTproBNP measurement or with more than 3 missing variables for risk estimation were excluded. Three contemporary web-based HF risk scores were evaluated: MAGGIC-HF, Seattle HF Model (SHFM) and the Barcelona Bio-HF Calculator containing NTproBNP (BCN Bio-HF). Risk of all-cause death at one year and at 3 years were calculated at baseline and re-evaluated after 12-month management in a multidsiscipli...

Natriuretic peptide dynamics with remote pulmonary artery pressure monitoring

European Heart Journal, 2021

Background Real-life clinical practice has confirmed the value of pulmonary artery (PA) pressure-... more Background Real-life clinical practice has confirmed the value of pulmonary artery (PA) pressure-guided therapy in patients with heart failure (HF) and history of repeated HF hospitalizations (HFH), to greater extent to that reported in the pivotal clinical trial CHAMPION-HF. The value of hemodynamic monitoring in a population of patients with HF and elevated natriuretic peptides, but without recent HFH, is unknown. Objective To assess N-terminal-pro-brain natriuretic peptide (NTproBNP) dynamics before and 6 months after PA pressure sensor implantation. Methods Ten patients managed in a multidisciplinary HF clinic implanted with the CardioMEMS PA pressure sensor were consecutively included from June 2019 to July 2020. Mean age was 63.1±23.5 years, 30% were women, 40% had HF with reduced EF (EF <40%). NTproBNP was measured at baseline and six months after sensor implantation. Wilcoxon matched-pairs signed-rank test was used to compare NTproBNP values at baseline and at 6 months. F...

Scientific Reports, Jan 12, 2021

To assess mortality trends at 1 and 3 years from 2001 to 2018 in a real-life cohort of HF outpati... more To assess mortality trends at 1 and 3 years from 2001 to 2018 in a real-life cohort of HF outpatients from different etiologies with depressed and preserved LVEF. A total of 2368 consecutive patients with HF (mean age 66.4 ± 12.9 years, 71% men, 15.4% with preserved LVEF) admitted to a HF clinic from August 2001 to September 2018 were included in the study. Patients were divided into five quintiles (Q) according to the period of admission. Trends for all-cause and cardiovascular mortality from Q1 to Q5 were assessed by linear regression. Patients with LVEF < 50% had a progressive decrease in the rates of all-cause and cardiovascular death at 1 year (12.1% in Q1 to 6.5% in Q5, p = 0.003; and 8.4% in Q1 to 3.8% in Q5, p = 0.007, respectively) and 3 years (30.5% in Q1 to 17.0% in Q5, p = 0.003; and 23.9% in Q1 to 9.8% in Q5, p = 0.003, respectively). These trends remained significant after adjusting for clinical characteristics and risk. No significant trend in mortality was observed in patients with LVEF ≥ 50%. In a cohort of real-life ambulatory patients with HF, mortality progressively declined in patients with LVEF < 50%, but the same trend was not observed in patients with preserved LVEF. Over the last three decades, since the introduction of angiotensin-converting enzyme inhibitors (ACEIs), there has been a progressive reduction in mortality rates across trials testing new therapies in patients with heart failure (HF) and reduced left ventricular ejection fraction (LVEF) . Therefore, current guidelines recommend the use of drugs inhibiting the neurohormonal axis and devices, such as implantable cardioverter defibrillator (ICD) and cardiac resynchronization therapy (CRT), to prolong survival in patients with HF and reduced LVEF (HFrEF) . Despite advances in HF management, which also include the implementation of HF clinics and specialized HF teams, the prognosis is still poor in the real-life setting. Data from registries indicate that, regardless of ejection fraction, mortality in HF patients can be as high as 75% at 5 years 12 , a rate that is significantly higher than in clinical trials, in which patients are usually younger and have fewer comorbidities. In addition, no improvement in survival has been observed across trials enrolling patients with HF with preserved LVEF (HFpEF). Furthermore, despite encouraging results from recent studies, no convincing evidence-based therapy for HFpEF has been identified . Thus, mortality from HF remains a challenge in real-world practice. In the present study, we assessed mortality trends at 1 and 3 years, from 2001 to 2018, in a real-life cohort of HF outpatients with depressed and preserved LVEF. Study population and outcomes. All consecutive ambulatory patients admitted to a structured multidisciplinary HF clinic at a university hospital between August 2001 and September 2018, regardless of aetiology, were considered for the study. During the 19-year study period, the clinical pathways and referral geographic area, covering ~ 850,000 inhabitants in the northern Barcelona Metro Area, remained stable. Patients were referred to the HF clinic mostly by the Cardiology or Internal Medicine Departments, and to a lesser extent by the Emergency Department or other hospital departments. The criteria for referral to the HF clinic were HF

BMC Neurology, Oct 2, 2013

Background: Silent brain infarcts are detected by neuroimaging in up to 20% of asymptomatic patie... more Background: Silent brain infarcts are detected by neuroimaging in up to 20% of asymptomatic patients based on population studies. They are five times more frequent than stroke in general population, and increase significantly both with advancing age and hypertension. Moreover, they are independently associated with the risk of future stroke and cognitive decline. Despite these numbers and the clinical consequences of silent brain infarcts, their prevalence in Mediterranean populations is not well known and their role as predictors of future cerebrovascular and cardiovascular events in hypertensive remains to be determined. ISSYS (Investigating Silent Strokes in Hypertensives: a magnetic resonance imaging study) is an observational crosssectional and longitudinal study aimed to: 1-determine the prevalence of silent cerebrovascular infarcts in a large cohort of 1000 hypertensives and to study their associated factors and 2-to study their relationship with the risk of future stroke and cognitive decline. Methods/Design: Cohort study in a randomly selected sample of 1000 participants, hypertensive aged 50 to 70 years old, with no history of previous stroke or dementia. On baseline all participants will undergo a brain MRI to determine the presence of brain infarcts and other cerebrovascular lesions (brain microbleeds, white matter changes and enlarged perivascular spaces) and will be also tested to determine other than brain organ damage (heart-left ventricular hypertrophy, kidney-urine albumin to creatinine ratio, vessels-pulse wave velocity, ankle brachial index), in order to establish the contribution of other subclinical conditions to the risk of further vascular events. Several sub-studies assessing the role of 24 hour ambulatory BP monitoring and plasma or genetic biomarkers will be performed. Follow-up will last for at least 3 years, to assess the rate of further stroke/transient ischemic attack, other cardiovascular events and cognitive decline, and their predictors.

Quality of life in patients with heart failure and improved ejection fraction: one‐year changes and prognosis

ESC Heart Failure

European Heart Journal

Background Alcoholic Cardiomyopathy (ACM) remains a prevalent form of toxic-induced heart damage.... more Background Alcoholic Cardiomyopathy (ACM) remains a prevalent form of toxic-induced heart damage. Whether ACM prognosis depends on the persistence of alcohol consumption is a matter of debate. Purpose We sought to determine predictors of adverse events during long-term follow-up and left ventricular ejection fraction (LVEF) changes between abstainers and non-abstainers. Methods Consecutive patients admitted to a HF clinic from 2001 to 2020 with ACM were included. The primary endpoint was the composite of all-cause death or HF hospitalization. HF hospitalization was analyzed as a secondary outcome. Changes in LVEF at 1- and 3-years follow-up according to discontinuation of alcohol consumption was also analyzed. Multivariable Cox regression analyses were performed using the competing risk strategy for the secondary endpoint. Results A total of 122 patients were included with a mean age of 57.8±10.0 years and 95.1% (n=116) of males. The mean LVEF was 27.5% ± 10.6 and 11.5% (n=14) exhib...

ESC Heart Failure

AimsPrior studies have not fully characterized the haemodynamic effects of the angiotensin recept... more AimsPrior studies have not fully characterized the haemodynamic effects of the angiotensin receptor‐neprilysin inhibitor (ARNI) sacubitril/valsartan in heart failure with preserved ejection fraction and pulmonary hypertension (HFpEF–PH). The aim of the Treatment of PH With Angiotensin II Receptor Blocker and Neprilysin Inhibitor in HFpEF Patients With CardioMEMS Device (ARNIMEMS‐HFpEF) study is to assess pulmonary artery pressure (PAP) dynamics by means of implanted PAP monitors in patients with HFpEF–PH treated with sacubitril/valsartan.Methods and resultsThis single‐arm, investigator‐initiated, interventional study included 14 consecutive ambulatory symptomatic HFpEF–PH patients who underwent CardioMEMS implantation prior to enrolment [mean ejection fraction 60.4 ± 7.2%, baseline mean PAP (mPAP) 33.9 ± 7.6 mmHg]. Daily PAP values were examined during three periods: a 6 week period after CardioMEMS implantation and before sacubitril/valsartan treatment (pre‐ARNI), a 6 week period w...

Nutrients

Background: The Global Leadership Initiative on Malnutrition (GLIM) criteria were recently propos... more Background: The Global Leadership Initiative on Malnutrition (GLIM) criteria were recently proposed to build a global consensus on the diagnostic criteria for malnutrition. This study aimed to evaluate the GLIM criteria for its prognostic significance in outpatients with heart failure (HF), and to compare them to a previous validated method, such as the Mini Nutritional Assessment (MNA). Methods: This was a post hoc observational analysis of a prospectively recruited cohort, which included 151 subjects that attended an outpatient HF clinic. At baseline, all patients completed the nutritional screening MNA short form and the nutritional assessment MNA. In a post hoc analysis, we evaluated the GLIM criteria at baseline. The outcomes were based on data from a five-year follow-up. The primary endpoint was all-cause mortality. Secondary endpoints were cardiovascular (CV) mortality and recurrent HF-related hospitalizations. We also investigated whether the GLIM criteria had better prognos...

Scientific Reports, 2021

Evidence regarding any association of HDL-particle (HDL-P) derangements and HDL-cholesterol conte... more 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 < 0.0...

European Heart Journal, 2021

Background N-terminal pro-brain natriuretic peptide (NT-proBNP) predicts mortality and the develo... more Background N-terminal pro-brain natriuretic peptide (NT-proBNP) predicts mortality and the development of heart failure (HF) in hypertrophic cardiomyopathy (HCM), however, evidence regarding soluble interleukin-1 receptor-like 1 (ST2) in this population is lacking. Purpose To assess the ST2 and NT-proBNP significance for risk stratification of patients with HCM during long-term follow-up. Methods We prospectively enrolled a cohort of consecutive patients with HCM admitted to an ambulatory HF Unit in a Tertiary University Hospital. All patients had clinical and echocardiographic evaluation and measurement of NT-proBNP and ST2 at inclusion. The primary endpoint was the composite of all-cause death or HF-related hospitalization. Results 103 patients were enrolled, 68% (n=70) males with a median (IQR) age of 60 (50–71) years. The median (IQR) of ST2 was 31.5 (IQR: 24.5 – 40.7) pg/mL. During a median follow-up of 2.5 years, 17 patients had the primary endpoint. Both, NT-proBNP and ST2 (b...

Valor pronóstico de la ecografía de pulmón en pacientes ambulatorios con insuficiencia cardiaca crónica estable

Revista Española de Cardiología, 2020

Resumen Introduccion y objetivos La utilidad de la ecografia pulmonar (EP) en la insuficiencia ca... more Resumen Introduccion y objetivos La utilidad de la ecografia pulmonar (EP) en la insuficiencia cardiaca (IC) aguda esta bien definida, pero no asi en la IC cronica. Este estudio investigo el valor pronostico de la EP en pacientes estables con IC cronica. Metodos Se incluyo a pacientes ambulatorios consecutivos con visita programada en una unidad de IC. La EP se realizo in situ, con los datos clinicos enmascarados, y evaluo 8 areas toracicas. La suma de lineas B en todas las areas pulmonares y los cuartiles de dicha adicion se utilizaron para los analisis de regresion lineal y de Cox. Los objetivos principales fueron el compuesto de muerte por cualquier causa u hospitalizacion por IC y mortalidad por cualquier causa. Resultados Se incluyo a 577 individuos (edad, 69 ± 12 anos; el 72% varones). La media de lineas B fue de 5 ± 6. Durante un seguimiento de 31 ± 7 meses, en 157 pacientes se produjo el resultado compuesto y 111 fallecieron. Tener ≥ 8 lineas B (Q4) doblo el riesgo de padecer el evento compuesto (p Conclusiones La EP identifico a pacientes con IC cronica estable y alto riesgo de muerte u hospitalizacion por IC.

European Heart Journal, 2018

Chronic heart failure-pathophysiology and mechanisms 1189 for indexed LV mass, indexed LA volume,... more Chronic heart failure-pathophysiology and mechanisms 1189 for indexed LV mass, indexed LA volume, mean E/e' and systolic blood pressure (B=-0.87 and B=0.78, P<0.001). Conclusions: HFpEF is characterized by impaired LA reservoir and pump function and increased stiffness which contribute to exercise mediated rises in PCWP. These markers may be of diagnostic potential and may be useful measures in studies of novel interventions. P5656 Heart failure with preserved ejection fraction (HFpEF) infrequently evolves towards a HFpEF-declined phenotype

Frontiers in Cardiovascular Medicine, Jan 5, 2021

Important differences in comorbidities and clinical characteristics exist between women and men w... more Important differences in comorbidities and clinical characteristics exist between women and men with heart failure (HF). In particular, differences in the kinetics of biological circulating biomarkers-a critical component of cardiovascular care-are highly relevant. Most circulating HF biomarkers are assessed daily by clinicians without taking sex into account, despite the multiple gender-related differences observed in plasma concentrations. Even in health, compared to men, women tend to exhibit higher levels of natriuretic peptides and galectin-3 and lower levels of cardiac troponins and the cardiac stress marker, soluble ST2. Many biological factors can provide a reliable explanation for these differences, like body composition, fat distribution, or menopausal status. Notwithstanding, these sex-specific differences in biomarker levels do not reflect different pathobiological mechanisms in HF between women and men, and they do not necessarily imply a need to use different diagnostic cut-off levels in clinical practice. To date, the sex-specific prognostic value of HF biomarkers for risk stratification is an unresolved issue that future research must elucidate. This review outlines current evidence regarding gender-related differences in circulating biomarkers widely used in HF, the pathophysiological mechanisms underlying these differences, and their clinical relevance.

European Heart Journal, Oct 1, 2022

Cardiac failure review, Jun 23, 2022

Heart failure with preserved ejection fraction (HFpEF) is a heterogeneous disorder developing fro... more Heart failure with preserved ejection fraction (HFpEF) is a heterogeneous disorder developing from multiple aetiologies with overlapping pathophysiological mechanisms. HFpEF diagnosis may be challenging, as neither cardiac imaging nor physical examination are sensitive in this situation. Here, we review biomarkers of HFpEF, of which the best supported are related to myocardial stretch and injury, including natriuretic peptides and cardiac troponins. An overview of biomarkers of inflammation, extracellular matrix derangements and fibrosis, senescence, vascular dysfunction, anaemia/iron deficiency and obesity is also provided. Finally, novel biomarkers from -omics technologies, including plasma metabolites and circulating microRNAs, are outlined briefly. A cardiac-centred approach to HFpEF diagnosis using natriuretic peptides seems reasonable at present in clinical practice. A holistic approach including biomarkers that provide information on the non-cardiac components of the HFpEF syndrome may enrich our understanding of the disease and may be useful in classifying HFpEF phenotypes or endotypes that may guide patient selection in HFpEF trials.

Journal of Clinical Medicine, Jan 31, 2022

We assessed differences in long-term all-cause and cardiovascular (CV) mortality in heart failure... more We assessed differences in long-term all-cause and cardiovascular (CV) mortality in heart failure (HF) outpatients based on the etiology of HF. Consecutive patients admitted to the HF Clinic from August 2001 to September 2019 (N = 2587) were considered for inclusion. HF etiology was divided into ischemic heart disease (IHD), dilated cardiomyopathy (DCM), hypertensive heart disease, alcoholic cardiomyopathy, drug-induced cardiomyopathy (DICM), valvular heart disease, and hypertrophic cardiomyopathy. All-cause death and CV death were the primary end points. Among 2387 patients included in the analysis (mean age 66.5 ± 12.5 years, 71.3% men), 1317 deaths were recorded (731 from CV cause) over a maximum follow-up of 18 years (median 4.1 years, interquartile range (IQR) 2-7.8). Considering IHD as the reference, only DCM had a lower risk of all-cause death (adjusted hazard ratio (aHR) 0.68, 95% confidence interval (CI) 0.56-0.83, p < 0.001), and only DICM had a higher risk of all-cause death (aHR 1.47, 95% CI 1.02-2.11, p = 0.04). However, almost all etiologies had a significantly lower risk of CV death than IHD. Among the studied HF etiologies, DCM and DICM have the lowest and highest risk of all-cause death, respectively, whereas IHD has the highest adjusted risk of CV death.

Circulation-heart Failure, Mar 1, 2019

BACKGROUND: Long-term trajectories of left ventricular ejection fraction (LVEF) in heart failure ... more BACKGROUND: Long-term trajectories of left ventricular ejection fraction (LVEF) in heart failure (HF) patients with preserved EF (HFpEF) remain unclear. Our objective was to assess long-term longitudinal trajectories in consecutive HFpEF patients and the prognostic impact of LVEF dynamic changes over time. Consecutive ambulatory HFpEF patients admitted to a multidisciplinary HF Unit were prospectively evaluated by 2-dimensional echocardiography at baseline and at 1, 3, 5, 7, 9, and 11 years of follow-up. Exclusion criteria were patients having a previous known LVEF <50%, patients undergoing only 1 echocardiogram study, and those with a diagnosis of dilated, noncompaction, alcoholic, or toxic cardiomyopathy. One hundred twenty-six patients (age, 71±13 years; 63% women) were included. The main pathogeneses were valvular disease (36%) and hypertension (28%). Atrial fibrillation was present in 67 patients (53%). The mean number of echocardiographies performed was 3±1.2 per patient. Locally weighted error sum of squares curves showed a smooth decrease of LVEF during the 11-year follow-up that was statistically significant in linear mixed-effects modeling (P=0.01). Ischemic patients showed a higher decrease than nonischemics. The great majority (88.9%) of patients remained in the HFpEF category during follow-up; 9.5% evolved toward HF with midrange LVEF, and only 1.6% dropped to HF with reduced LVEF. No significant relationship was found between LVEF dynamics in the immediate preceding period and mortality. CONCLUSIONS: LVEF remained ≥50% in the majority of patients with HFpEF for ≤11 years. Only 1.6% of patients evolved to HF with reduced LVEF. Dynamic LVEF changes were not associated with mortality.

European Heart Journal, Aug 2, 2013

Cardiovascular Diabetology, Mar 23, 2020

Background: Left ventricular ejection fraction (LVEF) trajectories and functional recovery with c... more Background: Left ventricular ejection fraction (LVEF) trajectories and functional recovery with current heart failure (HF) management is increasingly recognized. Type 2 diabetes mellitus (T2D) leads to a worse prognosis in HF patients. However, it is unknown whether T2D interferes with LVEF trajectories. The aim of this study was to prospectively assess very long-term (up to 15 years) LVEF trajectories in patients with and without T2D and underlying HF. Methods: Ambulatory patients admitted to a multidisciplinary HF clinic were prospectively evaluated by scheduled two-dimensional echocardiography at baseline, 1 year, and then every 2 years afterwards, up to 15 years. Statistical analyses of LVEF change with time were performed using the linear mixed effects (LME) models, and locally weighted error sum of squares (Loess) curves were plotted. Results: Of the 1921 patients, 461 diabetic and 699 non-diabetic patients with LVEF < 50% were included in the study. The mean number of echocardiography measurements performed in diabetic patients was 3.3 ± 1.6. Early LVEF recovery was similar in diabetic and non-diabetic patients, but Loess curves showed a more pronounced inverted U shape in diabetics with a more pronounced decline after 9 years. LME analysis showed a statistical interaction between T2D and LVEF trajectory over time (p = 0.009), which was statistically significant in patients with ischemic etiologies (p < 0.001). Other variables that showed an interaction between LVEF trajectories and T2D were male sex (p = 0.04) and HF duration (p = 0.008). Conclusions: LVEF trajectories in T2D patients with depressed systolic function showed a pronounced inverted U shape with a marked decline after 9 years. Diabetic cardiomyopathy may underlie the functional decline observed.

Evolocumab has no effects on heart failure with reduced ejection fraction injury biomarkers: The EVO‐HF trial

European Journal of Heart Failure

AimPatients with heart failure with reduced ejection fraction (HFrEF) have not been shown to bene... more AimPatients with heart failure with reduced ejection fraction (HFrEF) have not been shown to benefit from statins. We hypothesized that, by limiting disease progression in stable HFrEF of ischaemic etiology, the proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor evolocumab could reduce circulating troponin levels, a surrogate biomarker of myocyte injury and atherosclerosis progression.Methods and resultsThe EVO‐HF multicentre prospective randomized trial compared evolocumab (420 mg/month administered subcutaneously) plus guideline‐directed medical therapy (GDMT; n = 17) versus GDMT alone (n = 22) for 1 year in patients with stable coronary artery disease and left ventricular ejection fraction (LVEF) <40%, ischaemic aetiology, New York Heart Association class II, N‐terminal pro‐B‐type natriuretic peptide (NT‐proBNP) ≥400 pg/ml, high‐sensitivity troponin T (hs‐TnT) >10 pg/ml, low‐density lipoprotein cholesterol (LDL‐C) ≥70 mg/dl. The primary endpoint was change in h...

How mortality risk estimated by MAGGIC-HF, SHFM and BCN-Bio HF scores is modified after 12-month management in a multidisciplinary HF Clinic

European Heart Journal, 2020

Heart failure (HF) contemporary management has significantly improved over the past two decades l... more Heart failure (HF) contemporary management has significantly improved over the past two decades leading to better survival. How application of the contemporary HF management guidelines affects the risk of death estimated by available web-based risk scores is not elucidated. To assess changes in mortality risk prediction after a after a 12-month management period in a multidisciplinary HF Clinic. Out of 1,689 consecutive patients with HF admitted at our ambulatory HF Clinic from May 2006 to November 2018, those who completed one year follow-up were considered for the study. Patients without NTproBNP measurement or with more than 3 missing variables for risk estimation were excluded. Three contemporary web-based HF risk scores were evaluated: MAGGIC-HF, Seattle HF Model (SHFM) and the Barcelona Bio-HF Calculator containing NTproBNP (BCN Bio-HF). Risk of all-cause death at one year and at 3 years were calculated at baseline and re-evaluated after 12-month management in a multidsiscipli...

Natriuretic peptide dynamics with remote pulmonary artery pressure monitoring

European Heart Journal, 2021

Background Real-life clinical practice has confirmed the value of pulmonary artery (PA) pressure-... more Background Real-life clinical practice has confirmed the value of pulmonary artery (PA) pressure-guided therapy in patients with heart failure (HF) and history of repeated HF hospitalizations (HFH), to greater extent to that reported in the pivotal clinical trial CHAMPION-HF. The value of hemodynamic monitoring in a population of patients with HF and elevated natriuretic peptides, but without recent HFH, is unknown. Objective To assess N-terminal-pro-brain natriuretic peptide (NTproBNP) dynamics before and 6 months after PA pressure sensor implantation. Methods Ten patients managed in a multidisciplinary HF clinic implanted with the CardioMEMS PA pressure sensor were consecutively included from June 2019 to July 2020. Mean age was 63.1±23.5 years, 30% were women, 40% had HF with reduced EF (EF <40%). NTproBNP was measured at baseline and six months after sensor implantation. Wilcoxon matched-pairs signed-rank test was used to compare NTproBNP values at baseline and at 6 months. F...

Scientific Reports, Jan 12, 2021

To assess mortality trends at 1 and 3 years from 2001 to 2018 in a real-life cohort of HF outpati... more To assess mortality trends at 1 and 3 years from 2001 to 2018 in a real-life cohort of HF outpatients from different etiologies with depressed and preserved LVEF. A total of 2368 consecutive patients with HF (mean age 66.4 ± 12.9 years, 71% men, 15.4% with preserved LVEF) admitted to a HF clinic from August 2001 to September 2018 were included in the study. Patients were divided into five quintiles (Q) according to the period of admission. Trends for all-cause and cardiovascular mortality from Q1 to Q5 were assessed by linear regression. Patients with LVEF < 50% had a progressive decrease in the rates of all-cause and cardiovascular death at 1 year (12.1% in Q1 to 6.5% in Q5, p = 0.003; and 8.4% in Q1 to 3.8% in Q5, p = 0.007, respectively) and 3 years (30.5% in Q1 to 17.0% in Q5, p = 0.003; and 23.9% in Q1 to 9.8% in Q5, p = 0.003, respectively). These trends remained significant after adjusting for clinical characteristics and risk. No significant trend in mortality was observed in patients with LVEF ≥ 50%. In a cohort of real-life ambulatory patients with HF, mortality progressively declined in patients with LVEF < 50%, but the same trend was not observed in patients with preserved LVEF. Over the last three decades, since the introduction of angiotensin-converting enzyme inhibitors (ACEIs), there has been a progressive reduction in mortality rates across trials testing new therapies in patients with heart failure (HF) and reduced left ventricular ejection fraction (LVEF) . Therefore, current guidelines recommend the use of drugs inhibiting the neurohormonal axis and devices, such as implantable cardioverter defibrillator (ICD) and cardiac resynchronization therapy (CRT), to prolong survival in patients with HF and reduced LVEF (HFrEF) . Despite advances in HF management, which also include the implementation of HF clinics and specialized HF teams, the prognosis is still poor in the real-life setting. Data from registries indicate that, regardless of ejection fraction, mortality in HF patients can be as high as 75% at 5 years 12 , a rate that is significantly higher than in clinical trials, in which patients are usually younger and have fewer comorbidities. In addition, no improvement in survival has been observed across trials enrolling patients with HF with preserved LVEF (HFpEF). Furthermore, despite encouraging results from recent studies, no convincing evidence-based therapy for HFpEF has been identified . Thus, mortality from HF remains a challenge in real-world practice. In the present study, we assessed mortality trends at 1 and 3 years, from 2001 to 2018, in a real-life cohort of HF outpatients with depressed and preserved LVEF. Study population and outcomes. All consecutive ambulatory patients admitted to a structured multidisciplinary HF clinic at a university hospital between August 2001 and September 2018, regardless of aetiology, were considered for the study. During the 19-year study period, the clinical pathways and referral geographic area, covering ~ 850,000 inhabitants in the northern Barcelona Metro Area, remained stable. Patients were referred to the HF clinic mostly by the Cardiology or Internal Medicine Departments, and to a lesser extent by the Emergency Department or other hospital departments. The criteria for referral to the HF clinic were HF

BMC Neurology, Oct 2, 2013

Background: Silent brain infarcts are detected by neuroimaging in up to 20% of asymptomatic patie... more Background: Silent brain infarcts are detected by neuroimaging in up to 20% of asymptomatic patients based on population studies. They are five times more frequent than stroke in general population, and increase significantly both with advancing age and hypertension. Moreover, they are independently associated with the risk of future stroke and cognitive decline. Despite these numbers and the clinical consequences of silent brain infarcts, their prevalence in Mediterranean populations is not well known and their role as predictors of future cerebrovascular and cardiovascular events in hypertensive remains to be determined. ISSYS (Investigating Silent Strokes in Hypertensives: a magnetic resonance imaging study) is an observational crosssectional and longitudinal study aimed to: 1-determine the prevalence of silent cerebrovascular infarcts in a large cohort of 1000 hypertensives and to study their associated factors and 2-to study their relationship with the risk of future stroke and cognitive decline. Methods/Design: Cohort study in a randomly selected sample of 1000 participants, hypertensive aged 50 to 70 years old, with no history of previous stroke or dementia. On baseline all participants will undergo a brain MRI to determine the presence of brain infarcts and other cerebrovascular lesions (brain microbleeds, white matter changes and enlarged perivascular spaces) and will be also tested to determine other than brain organ damage (heart-left ventricular hypertrophy, kidney-urine albumin to creatinine ratio, vessels-pulse wave velocity, ankle brachial index), in order to establish the contribution of other subclinical conditions to the risk of further vascular events. Several sub-studies assessing the role of 24 hour ambulatory BP monitoring and plasma or genetic biomarkers will be performed. Follow-up will last for at least 3 years, to assess the rate of further stroke/transient ischemic attack, other cardiovascular events and cognitive decline, and their predictors.

Quality of life in patients with heart failure and improved ejection fraction: one‐year changes and prognosis

ESC Heart Failure

European Heart Journal

Background Alcoholic Cardiomyopathy (ACM) remains a prevalent form of toxic-induced heart damage.... more Background Alcoholic Cardiomyopathy (ACM) remains a prevalent form of toxic-induced heart damage. Whether ACM prognosis depends on the persistence of alcohol consumption is a matter of debate. Purpose We sought to determine predictors of adverse events during long-term follow-up and left ventricular ejection fraction (LVEF) changes between abstainers and non-abstainers. Methods Consecutive patients admitted to a HF clinic from 2001 to 2020 with ACM were included. The primary endpoint was the composite of all-cause death or HF hospitalization. HF hospitalization was analyzed as a secondary outcome. Changes in LVEF at 1- and 3-years follow-up according to discontinuation of alcohol consumption was also analyzed. Multivariable Cox regression analyses were performed using the competing risk strategy for the secondary endpoint. Results A total of 122 patients were included with a mean age of 57.8±10.0 years and 95.1% (n=116) of males. The mean LVEF was 27.5% ± 10.6 and 11.5% (n=14) exhib...

ESC Heart Failure

AimsPrior studies have not fully characterized the haemodynamic effects of the angiotensin recept... more AimsPrior studies have not fully characterized the haemodynamic effects of the angiotensin receptor‐neprilysin inhibitor (ARNI) sacubitril/valsartan in heart failure with preserved ejection fraction and pulmonary hypertension (HFpEF–PH). The aim of the Treatment of PH With Angiotensin II Receptor Blocker and Neprilysin Inhibitor in HFpEF Patients With CardioMEMS Device (ARNIMEMS‐HFpEF) study is to assess pulmonary artery pressure (PAP) dynamics by means of implanted PAP monitors in patients with HFpEF–PH treated with sacubitril/valsartan.Methods and resultsThis single‐arm, investigator‐initiated, interventional study included 14 consecutive ambulatory symptomatic HFpEF–PH patients who underwent CardioMEMS implantation prior to enrolment [mean ejection fraction 60.4 ± 7.2%, baseline mean PAP (mPAP) 33.9 ± 7.6 mmHg]. Daily PAP values were examined during three periods: a 6 week period after CardioMEMS implantation and before sacubitril/valsartan treatment (pre‐ARNI), a 6 week period w...

Nutrients

Background: The Global Leadership Initiative on Malnutrition (GLIM) criteria were recently propos... more Background: The Global Leadership Initiative on Malnutrition (GLIM) criteria were recently proposed to build a global consensus on the diagnostic criteria for malnutrition. This study aimed to evaluate the GLIM criteria for its prognostic significance in outpatients with heart failure (HF), and to compare them to a previous validated method, such as the Mini Nutritional Assessment (MNA). Methods: This was a post hoc observational analysis of a prospectively recruited cohort, which included 151 subjects that attended an outpatient HF clinic. At baseline, all patients completed the nutritional screening MNA short form and the nutritional assessment MNA. In a post hoc analysis, we evaluated the GLIM criteria at baseline. The outcomes were based on data from a five-year follow-up. The primary endpoint was all-cause mortality. Secondary endpoints were cardiovascular (CV) mortality and recurrent HF-related hospitalizations. We also investigated whether the GLIM criteria had better prognos...

Scientific Reports, 2021

Evidence regarding any association of HDL-particle (HDL-P) derangements and HDL-cholesterol conte... more 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 < 0.0...

European Heart Journal, 2021

Background N-terminal pro-brain natriuretic peptide (NT-proBNP) predicts mortality and the develo... more Background N-terminal pro-brain natriuretic peptide (NT-proBNP) predicts mortality and the development of heart failure (HF) in hypertrophic cardiomyopathy (HCM), however, evidence regarding soluble interleukin-1 receptor-like 1 (ST2) in this population is lacking. Purpose To assess the ST2 and NT-proBNP significance for risk stratification of patients with HCM during long-term follow-up. Methods We prospectively enrolled a cohort of consecutive patients with HCM admitted to an ambulatory HF Unit in a Tertiary University Hospital. All patients had clinical and echocardiographic evaluation and measurement of NT-proBNP and ST2 at inclusion. The primary endpoint was the composite of all-cause death or HF-related hospitalization. Results 103 patients were enrolled, 68% (n=70) males with a median (IQR) age of 60 (50–71) years. The median (IQR) of ST2 was 31.5 (IQR: 24.5 – 40.7) pg/mL. During a median follow-up of 2.5 years, 17 patients had the primary endpoint. Both, NT-proBNP and ST2 (b...

Valor pronóstico de la ecografía de pulmón en pacientes ambulatorios con insuficiencia cardiaca crónica estable

Revista Española de Cardiología, 2020

Resumen Introduccion y objetivos La utilidad de la ecografia pulmonar (EP) en la insuficiencia ca... more Resumen Introduccion y objetivos La utilidad de la ecografia pulmonar (EP) en la insuficiencia cardiaca (IC) aguda esta bien definida, pero no asi en la IC cronica. Este estudio investigo el valor pronostico de la EP en pacientes estables con IC cronica. Metodos Se incluyo a pacientes ambulatorios consecutivos con visita programada en una unidad de IC. La EP se realizo in situ, con los datos clinicos enmascarados, y evaluo 8 areas toracicas. La suma de lineas B en todas las areas pulmonares y los cuartiles de dicha adicion se utilizaron para los analisis de regresion lineal y de Cox. Los objetivos principales fueron el compuesto de muerte por cualquier causa u hospitalizacion por IC y mortalidad por cualquier causa. Resultados Se incluyo a 577 individuos (edad, 69 ± 12 anos; el 72% varones). La media de lineas B fue de 5 ± 6. Durante un seguimiento de 31 ± 7 meses, en 157 pacientes se produjo el resultado compuesto y 111 fallecieron. Tener ≥ 8 lineas B (Q4) doblo el riesgo de padecer el evento compuesto (p Conclusiones La EP identifico a pacientes con IC cronica estable y alto riesgo de muerte u hospitalizacion por IC.

European Heart Journal, 2018

Chronic heart failure-pathophysiology and mechanisms 1189 for indexed LV mass, indexed LA volume,... more Chronic heart failure-pathophysiology and mechanisms 1189 for indexed LV mass, indexed LA volume, mean E/e' and systolic blood pressure (B=-0.87 and B=0.78, P<0.001). Conclusions: HFpEF is characterized by impaired LA reservoir and pump function and increased stiffness which contribute to exercise mediated rises in PCWP. These markers may be of diagnostic potential and may be useful measures in studies of novel interventions. P5656 Heart failure with preserved ejection fraction (HFpEF) infrequently evolves towards a HFpEF-declined phenotype