Publications by authors named "Marta António"

72 Publications

Prognostic value of lung ultrasound in chronic stable ambulatory heart failure patients.

Rev Esp Cardiol (Engl Ed) 2020 Aug 26. Epub 2020 Aug 26.

Servei de Cardiologia, Unitat d'Insuficiència Cardiaca, Hospital Universitari Germans Trias i Pujol, Badalona, Barcelona, Spain; Departament de Medicina, Universitat Autònoma de Barcelona, Barcelona, Spain; CIBERCV, Instituto de Salud Carlos III, Madrid, Spain. Electronic address:

Introduction And Objectives: The role of lung ultrasound (LUS) in acute heart failure (HF) has been widely studied, but little is known about its usefulness in chronic HF. This study assessed the prognostic value of LUS in a cohort of chronic HF stable ambulatory patients.

Methods: We included consecutive outpatients who attended a scheduled follow-up visit in a HF clinic. LUS was performed in situ. The operators were blinded to clinical data and examined 8 thoracic areas. The sum of B-lines across all lung zones and the quartiles of this addition were used for the analyses. Linear regression and Cox regression analyses were performed. The main clinical outcomes were a composite of all-cause death or hospitalization for HF and mortality from any cause.

Results: A total of 577 individuals were included (72% men; 69± 12 years). The mean number of B-lines was 5±6. During a mean follow-up of 31±7 months, 157 patients experienced the main clinical outcome and 111 died. Having ≥ 8 B-lines (Q4) doubled the risk of experiencing the composite primary event (P <.001) and increased the risk of death from any cause by 2.6-fold (P <.001). On multivariate analysis, the total sum of B-lines remained independent predictive factor of the composite endpoint (HR, 1.04; 95%CI, 1.02-1.06; P=.002) and of all-cause death (HR, 1.04; 95%CI, 1.02-1.07; P=.001), independently of whether or not N-terminal pro-B-type natriuretic peptide (NT-proBNP) was included in the model (P=.01 and P=.008, respectively), with a 3% to 4% increased risk for each 1-line addition.

Conclusions: LUS identified patients with stable chronic HF at high risk of death or HF hospitalization.
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http://dx.doi.org/10.1016/j.rec.2020.07.006DOI Listing
August 2020

Body mass index and outcomes in ischaemic versus non-ischaemic heart failure across the spectrum of ejection fraction.

Eur J Prev Cardiol 2020 Jun 2:2047487320927610. Epub 2020 Jun 2.

Fondazione Toscana G. Monasterio, Pisa, Italy.

Aims: Obesity is related to better prognosis in heart failure with either reduced (HFrEF; left ventricular ejection fraction (LVEF) <40%) or preserved LVEF (HFpEF; LVEF ≥50%). Whether the obesity paradox exists in patients with heart failure and mid-range LVEF (HFmrEF; LVEF 40-49%) and whether it is independent of heart failure aetiology is unknown. Therefore, we aimed to test the prognostic value of body mass index (BMI) in ischaemic and non-ischaemic heart failure patients across the whole spectrum of LVEF.

Methods: Consecutive ambulatory heart failure patients were enrolled in two tertiary centres in Italy and Spain and classified as HFrEF, HFmrEF or HFpEF, of either ischaemic or non-ischaemic aetiology. Patients were stratified into underweight (BMI <18.5 kg/m), normal-weight (BMI 18.5-24.9 kg/m), overweight (BMI 25-29.9 kg/m), mild-obese (BMI 30-34.9 kg/m), moderate-obese (BMI 35-39.9 kg/m) and severe-obese (BMI ≥40 kg/m) and followed up for the end-point of five-year all-cause mortality.

Results: We enrolled 5155 patients (age 70 years (60-77); 71% males; LVEF 35% (27-45); 63% HFrEF, 18% HFmrEF, 19% HFpEF). At multivariable analysis, mild obesity was independently associated with a lower risk of all-cause mortality in HFrEF (hazard ratio, 0.78 (95% confidence interval (CI) 0.64-0.95),  = 0.020), HFmrEF (hazard ratio 0.63 (95% CI 0.41-0.96),  = 0.029), and HFpEF (hazard ratio 0.60 (95% CI 0.42-0.88),  = 0.008). Both overweight and mild-to-moderate obesity were associated with better outcome in non-ischaemic heart failure, but not in ischaemic heart failure.

Conclusions: Mild obesity is independently associated with better survival in heart failure across the whole spectrum of LVEF. Prognostic benefit of obesity is maintained only in non-ischaemic heart failure.
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http://dx.doi.org/10.1177/2047487320927610DOI Listing
June 2020

Pulmonary hypertension and right ventricular dysfunction in heart failure: prognosis and 15-year prospective longitudinal trajectories in survivors.

Eur J Heart Fail 2020 07 25;22(7):1214-1225. Epub 2020 May 25.

Heart Failure Unit, Hospital Universitari Germans Trias i Pujol, Badalona, Spain.

Aims: Systolic pulmonary artery pressure (SPAP), tricuspid annular plane systolic excursion (TAPSE), and TAPSE/SPAP ratio trajectories are not fully characterized in chronic heart failure (HF). We assessed very long-term longitudinal SPAP, TAPSE and TAPSE/SPAP trajectories in HF patients, and their dynamic changes in outcomes.

Methods And Results: Prospective, consecutive, observational registry of real-life HF patients, performing echocardiography studies at baseline and according to a prospectively structured schedule after 1 year, and then every 2 years, up to 15 years. Pulmonary hypertension (PH) was defined as SPAP ≥40 mmHg; right ventricular dysfunction (RVD) was defined at TAPSE ≤16 mm; and TAPSE/SPAP ratio was dichotomized at 0.36 mm/mmHg. The clinical endpoints were all-cause death, the composite endpoint of mortality or HF hospitalization and the number of recurrent HF hospitalizations. The study cohort included 1557 patients. Long-term SPAP trajectory Loess curves were U-shaped with a nadir at 7 years. TAPSE Loess curves showed a marked rise during the first year, with stabilization thereafter. TAPSE/SPAP ratio Loess splines were similar to the later with a smooth decline towards the end. Patients who died had higher SPAP, lower TAPSE and lower TAPSE/SPAP ratio in the preceding period than survivors. Baseline PH and/or RVD were independently associated with mortality and HF-related hospitalizations, and the persistence of one or both entities at 1 year conferred a worse long-term prognosis.

Conclusions: Long-term trajectories for SPAP, TAPSE and TAPSE/SPAP ratio are reported in patients with chronic HF. An increasing SPAP and declining TAPSE and TAPSE/SPAP ratio in the preceding period is associated with higher mortality.
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http://dx.doi.org/10.1002/ejhf.1862DOI Listing
July 2020

Use of intravenous iron in patients with iron deficiency and chronic heart failure: Real-world evidence.

Eur J Intern Med 2020 10 19;80:91-98. Epub 2020 May 19.

Cardiovascular Diseases Research Group, Bellvitge Biomedical Research Institute (IDIBELL), L'Hospitalet de Llobregat, Barcelona, Spain; Community Heart Failure Program, Department of Cardiology, Hospital Universitari de Bellvitge, L'Hospitalet de Llobregat, Barcelona, Spain. Electronic address:

Introduction And Objectives: Treatment with intravenous iron in patients with heart failure (HF) and iron deficiency (ID) improves symptoms, however its impact on survival and safety is unknown. We aimed to evaluate the management of ID and anemia with intravenous iron in patients with HF and long-term safety of intravenous iron.

Methods: We evaluated anemia and ID in patients with chronic HF at 3 university hospitals. Anemia was defined using the World Health Organization definition and ID was defined as ferritin <100 ug/L or a Transferrin Saturation <20% if ferritin between 100 and 299 ug/L. We assessed treatment with intravenous iron during follow-up and its association with mortality and HF hospitalizations using multivariate cox regression analysis.

Results: We included 2,114 patients, median age 72 years and 57% had reduced left ventricular ejection fraction. ID was present in 55% and ID and anemia in 29%. Treatment with intravenous iron was used in 24% of patients with ID and 34% of patients with ID and anemia. In patients with ID, after multivariate adjustment, treatment with intravenous iron was associated with lower all-cause mortality: HR = 0.38 (0.28-0.56), lower cardiovascular mortality: HR = 0.34 (0.20-0.57) and no differences in HF hospitalizations: HR = 1.15 (0.88-1.50). Similar outcomes were found for patients with anemia and ID.

Conclusions: In a real-world cohort of patients with HF, treatment with intravenous iron was used in one third of patients with ID and anemia and appears safe in mid-term follow-up.
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http://dx.doi.org/10.1016/j.ejim.2020.04.031DOI Listing
October 2020

Long-term LVEF trajectories in patients with type 2 diabetes and heart failure: diabetic cardiomyopathy may underlie functional decline.

Cardiovasc Diabetol 2020 03 23;19(1):38. Epub 2020 Mar 23.

Heart Failure Unit, Hospital Universitari Germans Trias i Pujol, Badalona, Barcelona, Spain.

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.
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http://dx.doi.org/10.1186/s12933-020-01011-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7092450PMC
March 2020

Mini Nutritional Assessment Short Form is a morbi-mortality predictor in outpatients with heart failure and mid-range left ventricular ejection fraction.

Clin Nutr 2020 Nov 27;39(11):3395-3401. Epub 2020 Feb 27.

ICREC Research Program, Fundació Institut d´Investigació en Ciències de la Salut Germans Trias i Pujol (IGTP), Badalona, Spain; Heart Failure Unit and Cardiology Department, Hospital Universitari Germans Trias i Pujol, Badalona, Spain; Department of Medicine, Universitat Autònoma de Barcelona, Barcelona, Spain; CIBERCV, Instituto de Salud Carlos III, Madrid, Spain.

Background & Aims: Nutritional status is an important prognostic factor in patients with heart failure (HF). In a pilot study we previously observed that the Mini Nutritional Assessment Short Form tool (MNA-SF) was the best approach for the screening of nutritional status in HF outpatients over other screening tools. The current study aimed to determine whether the MNA-SF has prognostic value in outpatients with HF and whether the impact of malnutrition differs depending on left ventricular ejection fraction (LVEF).

Methods: Prospective study performed in outpatients attending a HF clinic at a university hospital. All subjects completed the MNA-SF at study entry. The primary endpoint was all-cause mortality. Secondary end-points were the number of recurrent HF-related hospitalizations and the composite end-point of all-cause death or HF-related hospitalizations. Patients with malnutrition and at risk of malnutrition were merged and considered as having abnormal nutritional status for statistical analysis.

Results: From October 2016 to November 2017, 555 patients were included (age 69 ± 11.5 years, 71% male, LVEF 44.6 ± 13.2). Abnormal nutritional status was identified in 103 (18.6%) subjects. HF patients with preserved LVEF had a higher proportion of abnormal nutritional status (23%) than patients with HF and mid-range LVEF (HFmrEF) (16.4%) or those with HF with reduced LVEF (HFrEF) (15.9%.). During a mean follow-up of 23.8 ± 6.6 months, 99 patients died (17.8%), 74 were hospitalized due to HF (13.3%) and the composite end-point was observed in 181 (32.6%). In the univariate analysis, abnormal nutritional status was significantly associated with all-cause mortality (p = 0.02) and the composite end-point (p = 0.02) in the total cohort. However, in the multivariate analysis including age, sex, NYHA functional class, BMI, ischemic aetiology, diabetes, hypertension and HF duration, abnormal nutritional status remained significantly associated with all-cause mortality (HR 3.32 [95%CI 1.47-7.52], p = 0.004), and the composite end-point (HR 2.53 [95%CI 1.30-4.94], p = 0.006) only in HFmrEF patients. Patients with abnormal nutritional status suffered double the crude number of recurrent HF-related hospitalizations (16.4 vs. 8.4 per 100 patients-years, p < 0.001).

Conclusions: The implementation of MNA-SF as a routine screening tool allowed the detection of abnormal nutritional status in almost one out of five ambulatory HF patients. Nutritional status assessed by the MNA-SF was an independent predictor of all-cause death and the composite end-point of all-cause death or HF-related hospitalization in outpatients with HFmrEF. Furthermore, abnormal nutritional status was significantly related to recurrent hospitalizations across the HF spectrum.
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http://dx.doi.org/10.1016/j.clnu.2020.02.031DOI Listing
November 2020

Trends in modes of death in heart failure over the last two decades: less sudden death but cancer deaths on the rise.

Eur J Heart Fail 2019 10 30;21(10):1259-1266. Epub 2019 Jul 30.

Heart Failure Clinic and Cardiology Service, University Hospital Germans Trias i Pujol, Badalona, Spain.

Aims: Better management of heart failure (HF) over the past two decades has improved survival, mainly by reducing the incidence of death due to cardiovascular (CV) causes. Deaths due to non-CV causes, particularly cancer, may be increasing. This study explored the modes of death of consecutive patients who attended a HF clinic over 17 years.

Methods And Results: A total of 935 deaths were ascertained from 2002 to 2018 among 1876 patients (mean age 65.8 ± 12.5 years, 75% men, left ventricular ejection fraction < 50%) admitted to our HF clinic. Median follow-up was 4.2 years [1.9-7.8]. Mode of death was curated from patient health records and verified by the Catalan and Spanish health system databases. Trends for every mode of death were assessed by polynomial regression. Two trends were observed: a significant reduction in sudden death (P = 0.03) without changes in HF progression as mode of death (P = 0.26), and a significant increase in non-CV modes of death (P < 0.001). Non-CV deaths accounted for 17.4% of deaths in 2002 and 65.8% of deaths in 2018. A total 138 deaths were due to cancer (37% of non-CV deaths). A significant trend was observed towards a progressive increase in cancer deaths over time (P = 0.002). The main mode of cancer mortality was lung cancer.

Conclusions: The modes of death in HF have shifted over the last two decades. Patients with HF die less due to sudden death and more due to non-CV causes, mainly cancer. Whether HF triggers cancer, or cancer develops in HF survivors, deserves further insight.
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http://dx.doi.org/10.1002/ejhf.1569DOI Listing
October 2019

A bio-clinical approach for prediction of sudden cardiac death in outpatients with heart failure: The ST2-SCD score.

Int J Cardiol 2019 10 23;293:148-152. Epub 2019 May 23.

Heart Failure Unit, Hospital Universitari Germans Trias i Pujol, Badalona, Barcelona, Spain; Cardiology Department, Hospital Universitari Germans Trias i Pujol, Badalona, Barcelona, Spain; Department of Medicine, Universitat Autònoma de Barcelona, Barcelona, Spain; CIBER Cardiovascular, Instituto de Salud Carlos III, Madrid, Spain. Electronic address:

Background: Sudden cardiac death (SCD) is one of the main modes of death in heart failure (HF) patients and its prediction remains a real challenge. Our aim was to assess the incidence of SCD at 5 years HF contemporary managed outpatients, and to find a simple prediction model for SCD.

Methods: SCD was considered any unexpected death, witnessed or not, occurring in a previously stable patient with no evidence of worsening HF or any other cause of death. A competing risk strategy was adopted using the Fine-Gray method of Cox regressions analyses that considered other causes of death as the competing event.

Results: The derivation cohort included 744 consecutive outpatients (72% men, age 67.9 ± 12.2 years, left ventricular ejection fraction [LVEF] 36% ± 14). During follow-up, 312 deaths occurred, 40 SCDs (5.4%). Age, haemoglobin, eGFR, HF duration, high-sensitivity troponin T, NTproBNP, and ST2 were associated with SCD in univariate analyses; HF duration (p = 0.006), eGFR (p < 0.001), LVEF <45% (p = 0.03), and ST2 (p = 0.006) remained in multivariable analysis. A predictive score (ST2-SCD) including dichotomous variables (ST2 > 45, LVEF <45%, HF duration >3 years, eGFR < 55, age ≥ 60 years and male sex) provided a Harrell's C-statistic of 0.82 (0.76-0.89)), reaching 0.87 (0.80-0.95) in the validation cohort (n = 149).

Conclusions: In contemporary managed HF, SCD occurred in 5.4% of outpatients, accounting for 12.8% of all deaths at 5 years. Of the 3 studied biomarkers, only ST2 remained independently associated with SCD. A model containing age, sex, ST2, eGFR, LVEF, and HF duration reasonably predicted 5-years risk of SCD.
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http://dx.doi.org/10.1016/j.ijcard.2019.05.046DOI Listing
October 2019

Impact of Treatment Modality on Vascular Function in Coarctation of the Aorta: The LOVE - COARCT Study.

J Am Heart Assoc 2019 04;8(7):e011536

7 Department of Cardiology Boston Children's Hospital and Harvard Medical School Boston MA.

Background Optimally treated patients with coarctation of the aorta remain at risk for late vascular dysfunction. The effect of treatment modality on vascular function is unknown. The LOVE-COARCT (Long-term Outcomes and Vascular Evaluation After Successful Coarctation of the Aorta Treatment) study was done to compare vascular function in patients with coarctation of the aorta treated with surgery, balloon dilation (BD), or stent implantation. Methods and Results In treated coarctation of the aorta patients without residual coarctation, we prospectively compared aortic stiffness by applanation tonometry and cardiac magnetic resonance; endothelial function by endothelial pulse amplitude testing; blood pressure ( BP ) phenotype by office BP , ambulatory BP monitoring, and BP response to exercise; left ventricular mass by cardiac magnetic resonance; and blood biomarkers of endothelial function, inflammation, vascular wall function, and extracellular matrix. Participants included 75 patients treated with surgery (n=28), BD (n=23), or stent (n=24). Groups had similar age at enrollment, coarctation of the aorta severity, residual gradient, and metabolic profile, but differed by age at treatment. Prevalence of systemic hypertension, aortic stiffness, endothelial function, and left ventricular mass were similar among treatment groups. However, BD patients had more-distensible ascending aortas, lower peak systolic BP during exercise, less impairment in diurnal BP variation, and lower inflammatory biomarkers. Results were unchanged after adjustment for potential confounders, including age at treatment. Conclusions In our cohort of patients without residual coarctation, treatment modality was not associated with major vascular outcomes, even though there were some favorable vascular characteristics in the BD patients. Although this suggests that choice of treatment modality should continue to be driven by likelihood of achieving a good anatomical result, more long-term studies are required to assess the clinical significance of the more-optimal results of secondary markers of vascular function in BD patients. Clinical Trial Registration URL : http://www.clinicaltrials.gov . Unique identifier: NCT 03262753.
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http://dx.doi.org/10.1161/JAHA.118.011536DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6509735PMC
April 2019

Heart Failure With Preserved Ejection Fraction Infrequently Evolves Toward a Reduced Phenotype in Long-Term Survivors.

Circ Heart Fail 2019 03;12(3):e005652

Heart Failure Unit, Hospital Universitari Germans Trias i Pujol, Badalona (Barcelona), Spain (J.L., M.d.A., M.D., E.Z, P.M., E.S.-V., J.S., A.B.-G.).

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.

Methods And Results: 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.
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http://dx.doi.org/10.1161/CIRCHEARTFAILURE.118.005652DOI Listing
March 2019

Airflow limitation in patients with heart failure: Prevalence and associated factors.

Med Clin (Barc) 2019 09 4;153(5):191-195. Epub 2019 Jan 4.

Servicio de Neumología, Hospital Universitari Germans Trias i Pujol, Badalona, Barcelona, España; Fundació Institut d'Investigació en Ciències de la Salut Germans Trias i Pujol, Badalona, Barcelona, España; Departament de Medicina, Universitat Autònoma de Barcelona, Barcelona, España; CibeRes - Ciber de Enfermedades Respiratorias, Bunyola, Mallorca, España.

Background: Chronic obstructive pulmonary disease and heart failure (HF) are 2 diseases with high morbidity and mortality. The coexistence of these two diseases is estimated to be frequent, but has been poorly studied.

Aim: To study the prevalence of airflow limitation in a sample of patients diagnosed with HF in follow-up in an HF unit and to assess their characteristics and comorbidities.

Methods: This is a prospective observational study. The patients who visited the HF Unit of the Hospital Universitari Germans Trias i Pujol between January 2014 and June 2015 were included consecutively. Respiratory functional tests were performed and clinical data were obtained.

Results: 118 patients were included in the study (age 67.2 years, 77.1% men). The prevalence of non-reversible airflow obstruction was 36.4%, with an underdiagnosis percentage of 67.4%. Patients with airflow limitation had an increase in comorbidities, but no worse prognosis.

Conclusion: The prevalence of airflow limitation in patients with HF is high, with a significant degree of underdiagnosis. It seems reasonable to recommend performing a screening spirometry in these patients.
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http://dx.doi.org/10.1016/j.medcli.2018.11.016DOI Listing
September 2019

Mini nutritional assessment is a better predictor of mortality than subjective global assessment in heart failure out-patients.

Clin Nutr 2019 12 10;38(6):2740-2746. Epub 2018 Dec 10.

ICREC Research Program, Fundació Institut d'Investigació en Ciències de la Salut Germans Trias i Pujol (IGTP), Badalona, Spain; CIBERCV, Instituto de Salud Carlos III, Madrid, Spain; Heart Failure Unit and Cardiology Department, Hospital Universitari Germans Trias i Pujol, Badalona, Spain; Department of Medicine, Universitat Autònoma de Barcelona, Barcelona, Spain.

Background & Aims: There is no consensus on the best method for nutritional screening and assessment in patients with heart failure (HF). This study aimed to determine which nutritional assessment method had the highest prognostic significance for patients with HF treated in outpatient clinics. We also aimed to identify a fast, reliable screening method for detecting malnutrition in these patients.

Methods: This prospective study included 151 subjects that attended an outpatient HF clinic at a university hospital. All patients completed three nutritional screening tools: the Malnutrition Universal Screening Tool (MUST), the MNA-short form (MNA-SF), and the Malnutrition Screening Tool (MST), and then, two nutritional assessment questionnaires: the Subjective Global Assessment (SGA) and the Mini Nutritional Assessment®(MNA). Patients were followed-up for 2 years. The primary endpoint was all-cause mortality.

Results: Malnutrition or nutritional risk was identified in 15.9% of patients with the SGA and in 25.1% of patients with the MNA. Age, New York Heart Association (NYHA) functional class, and MNA were the only independent all-cause death predictors after adjusting for age, gender, NYHA functional class, body mass index, Barthel index, 25-hydroxyvitamin D concentrations, treatment with angiotensin converting enzyme inhibitors or angiotensin II receptor blockers, and treatment with beta-blockers. The SGA could not independently predict all-cause mortality in a multivariate analysis that included the same covariates. The MNA-SF had the best sensitivity, specificity, and kappa coefficient for screening malnutrition, based on the MNA and the SGA as references, compared to the other screening methods.

Conclusions: In our cohort, malnutrition assessed by MNA, but not by SGA, was an independent predictor of mortality. MNA-SF showed remarkable sensitivity and specificity; thus, it might be a valuable tool for rapidly identifying malnutrition risk in outpatients with HF.
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http://dx.doi.org/10.1016/j.clnu.2018.12.001DOI Listing
December 2019

Importance of iron deficiency in patients with chronic heart failure as a predictor of mortality and hospitalizations: insights from an observational cohort study.

BMC Cardiovasc Disord 2018 11 1;18(1):206. Epub 2018 Nov 1.

Unidad de Insuficiencia Cardíaca, Hospital Universitari Germans Trias i Pujol, Universitat Autònoma de Barcelona, Badalona, Barcelona, Spain.

Background: Iron deficiency (ID) in patients with chronic heart failure (CHF) is considered an adverse prognostic factor. We aimed to evaluate if ID in patients with CHF is associated with increased mortality and hospitalizations.

Methods: We evaluated ID in patients with CHF at 3 university hospitals. ID was defined as absolute (ferritin < 100 μg/L) or functional (transferrin Saturation index < 20% and ferritin between 100 and 299 μg/L). We excluded patients who received treatment with intravenous Iron or Erythropoietin during follow-up. We evaluated if ID was a predictor of death or hospitalization due to heart failure or any cause using univariate and multivariate cox regression analysis.

Results: We included 1684 patients, 65% males, 38% diabetics, median age of 72 years, 37% in functional class III-IV and 30% of patients with a left ventricular ejection fraction > 45%. Patients were well treated, with 87% and 88% of patients receiving renin-angiotensin inhibitors and beta-blockers, respectively. Median transferrin saturation index was 20%, median ferritin 155 ng/mL and median haemoglobin 13 g/dL. ID was present in 53% of patients; in 35% it was absolute and in 18% functional. Median follow-up was 20 months. ID was a predictor of death, hospitalization due to heart failure or to any cause in univariate analysis but not after multivariate analysis. No differences were found between absolute or functional ID regarding prognosis.

Conclusion: In a real life population of patients with CHF and a high prevalence of heart failure with preserved ejection fraction, ID did not predict mortality or hospitalizations after adjustment for comorbidities, functional class and neurohormonal treatment.
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http://dx.doi.org/10.1186/s12872-018-0942-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6211465PMC
November 2018

Rationale and design of Long-term Outcomes and Vascular Evaluation after Successful Coarctation of the Aorta Treatment study.

Ann Pediatr Cardiol 2018 Sep-Dec;11(3):282-296

Department of Cardiology, Boston Children's Hospital, Harvard Medical School, Boston, USA.

Background: Coarctation of the aorta (CoA) can be treated using surgery, balloon angioplasty, or stent implantation. Although short-term results are excellent with all three treatment modalities, long-term cardiovascular (CV) morbidity and mortality remain high, likely due to persistently abnormal vascular function. The effects of treatment modality on long-term vascular function remain uncharacterized. The goal of this study is to assess vascular function in this patient population for comparison among the treatment modalities.

Methods: We will prospectively assess vascular Afunction in large and small arteries fusing multiple noninvasive modalities and compare the results among the three groups of CoA patients previously treated using surgery, balloon angioplasty, or stent implantation after frequency matching for confounding variables. A comprehensive vascular function assessment protocol has been created to be used in 7 centers. Our primary outcome is arterial stiffness measured by arterial tonometry. Inclusion and exclusion criteria have been carefully established after consideration of several potential confounders. Sample size has been calculated for the primary outcome variable.

Conclusion: Treatment modalities for CoA may have distinct impact on large and small arterial vascular function. The results of this study will help identify the treatment modality that is associated with the most optimal level of vascular function, which, in the long term, may reduce CV risk.
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http://dx.doi.org/10.4103/apc.APC_64_18DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6146860PMC
October 2018

Circulating monocyte subsets and heart failure prognosis.

PLoS One 2018 21;13(9):e0204074. Epub 2018 Sep 21.

Heart Failure Unit and Cardiology Service, Germans Trias i Pujol University Hospital, Badalona, Spain.

Monocytes are a heterogeneous population of effector cells with key roles in tissue integrity restoration and maintenance. Here, we explore the association of monocyte subsets and prognosis in patients with ambulatory heart failure (HF). Monocyte subsets were classified as classical (CD14++/CD16-), intermediate (CD14++/CD16+), or non-classical (CD14+/CD16++). Percentage distribution and absolute cell count were assessed in each subset, and multivariable Cox regression analyses were performed with all-cause death, HF-related hospitalization, and the composite end-point of both as dependent variables. 400 patients were consecutively included (72.8% male, age 69.4±12.2 years, 45.5% from ischemic aetiology, left ventricle ejection fraction (LVEF) 41.6% ±14.5, New York Heart Association (NYHA) class II 62.8% and III 30.8%). During a mean follow-up of 2.6±0.9 years, 107 patients died, 99 had a HF-related hospitalization and 160 suffered the composite end-point of all-cause death or HF-related hospitalization. Monocyte subsets assessed in percentages were not independently associated to any of the end-points. When considering number of cells/μL, intermediate subset was independently associated with an increase of all-cause death (HR 1.25 [95% CI 1,02-1.52], p = 0.03), and the composite end-point HR 1.20 [95% CI 1,03-1.40], p = 0.02). The presented findings show that absolute cell count of monocyte subsets was preferred over monocyte percentage for prognosis stratification for outpatients with HF. The intermediate monocyte subset provides information on increased risk of all-cause death and the composite end-point.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0204074PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6150659PMC
March 2019

Comorbidities, Fragility, and Quality of Life in Heart Failure Patients With Midrange Ejection Fraction.

Mayo Clin Proc Innov Qual Outcomes 2018 Jun 19;2(2):176-185. Epub 2018 Apr 19.

ICREC Research Program, Germans Trias i Pujol Research Institute in Health Sciences, Badalona, Spain.

Objective: To assess the effects of comorbidities, fragility, and quality of life (QOL) on long-term prognosis in ambulatory patients with heart failure (HF) with midrange left ventricular ejection fraction (HFmrEF), an unexplored area.

Patients And Methods: Consecutive patients prospectively evaluated at an HF clinic between August 1, 2001, and December 31, 2015, were retrospectively analyzed on the basis of left ventricular ejection fraction category. We compared patients with HFmrEF (n=185) to those with reduced (HFrEF; n=1058) and preserved (HFpEF; n=162) ejection fraction. Fragility was defined as 1 or more abnormal evaluations on 4 standardized geriatric scales (Barthel Index, Older Americans Resources and Services scale, Pfeiffer Test, and abbreviated-Geriatric Depression Scale). The QOL was assessed with the Minnesota Living with Heart Failure Questionnaire. A comorbidity score (0-7) was constructed. All-cause death, HF-related hospitalization, and the composite end point of both were assessed.

Results: Comorbidities and QOL scores were similar in HFmrEF (2.41±1.5 and 30.1±18.3, respectively) and HFrEF (2.30±1.4 and 30.8±18.5, respectively) and were higher in HFpEF (3.02±1.5, <.001, and 36.5±20.7, =.003, respectively). No statistically significant differences in fragility between HFmrEF (48.6%) and HFrEF (41.9%) (=.09) nor HFpEF (54.3%) (=.29) were found. In univariate analysis, the association of comorbidities, QOL, and fragility with the 3 end points was higher for HFmrEF than for HFrEF and HFpEF. In multivariate analysis, comorbidities were independently associated with the 3 end points (≤.001), and fragility was independently associated with all-cause death and the composite end point (<.001) in HFmrEF.

Conclusion: Comorbidities and fragility are independent predictors of outcomes in ambulatory patients with HFmrHF and should be considered in the routine clinical assessment of HFmrEF.
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http://dx.doi.org/10.1016/j.mayocpiqo.2018.02.004DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6124320PMC
June 2018

Dynamic Trajectories of Left Ventricular Ejection Fraction in Heart Failure.

J Am Coll Cardiol 2018 08;72(6):591-601

Heart Failure Unit, Hospital Universitari Germans Trias i Pujol, Badalona, Barcelona, Spain; Cardiology Department, Hospital Universitari Germans Trias i Pujol, Badalona, Barcelona, Spain; Department of Medicine, Universitat Autònoma de Barcelona, Barcelona, Spain; Centro de Investigatión Biomédica en Red (CIBER) Cardiovascular, Instituto de Salud Carlos III, Madrid, Spain. Electronic address:

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.
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http://dx.doi.org/10.1016/j.jacc.2018.05.042DOI Listing
August 2018

Uhl's disease: An uncommon presentation of a rare disease.

Rev Port Cardiol 2018 12 9;37(12):1007.e1-1007.e5. Epub 2018 Jul 9.

Cardiology Department, Santa Marta Hospital, Lisbon, Portugal.

Uhl's disease, also known as Uhl anomaly, is a rare disease secondary to selective but uncontrolled apoptosis of right ventricular myocytes during the perinatal period, after complete cardiac development, leading to the absence of right ventricular myocardium and the direct apposition of endocardium to epicardium without a myocardial layer in between, resulting in right ventricular failure. The present paper describes a case of Uhl's disease with an uncommon presentation. A 28-year-old man was admitted with dyspnea and cyanosis. Transthoracic echocardiography showed severe dilation of the right chambers, impaired right ventricular systolic function and a large ostium secundum atrial septal defect (ASD). Cardiac catheterization revealed pulmonary hypertension, with increased pulmonary capillary wedge pressure (mean 19mmHg) and Qp:QS 0.88:1. At this point, the authors considered that a main diagnosis of ASD could not explain the clinical features and hemodynamic data. A primary disease of the right ventricle was the most likely hypothesis and cardiac magnetic resonance imaging was performed, which demonstrated an extremely thin-walled right ventricle, with almost complete absence of right ventricular free wall myocardium, compatible with Uhl's disease.
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http://dx.doi.org/10.1016/j.repc.2017.06.025DOI Listing
December 2018

Advanced interatrial block predicts new-onset atrial fibrillation and ischemic stroke in patients with heart failure: The "Bayes' Syndrome-HF" study.

Int J Cardiol 2018 Nov 18;271:174-180. Epub 2018 May 18.

Heart Institute, Hospital Universitari Germans Trias i Pujol, Badalona, Spain; Department of Medicine, CIBERCV, Autonomous University of Barcelona, Barcelona, Spain. Electronic address:

Aims: Advanced interatrial block (IAB) is characterized by a prolonged (≥120 ms) and bimodal P wave in the inferior leads. The association between advanced IAB and atrial fibrillation (AF) is known as "Bayes' Syndrome", and there is scarce information about it in heart failure (HF). We examined the prevalence of IAB and whether advanced IAB could predict new-onset AF and/or stroke in HF patients.

Methods And Results: The prospective observational "Bayes' Syndrome-HF" study included consecutive outpatients with chronic HF. The primary endpoints were new-onset AF, ischemic stroke, and the composite of both. A secondary endpoint included all-cause death alone or in combination with the primary endpoint. Comprehensive multivariable Cox regression analyses were performed. Among 1050 consecutive patients, 536 (51.0%) were in sinus rhythm, 464 with a measurable P wave are the focus of this study. Two-hundred and sixty patients (56.0%) had normal atrial conduction, 95 (20.5%) partial IAB, and 109 (23.5%) advanced IAB. During a mean follow-up of 4.5 ± 2.1 years, 235 patients experienced all-cause death, new-onset AF, or stroke. In multivariable comprehensive Cox regression analyses, advanced IAB was associated with new-onset AF (HR 2.71 [1.61-4.56], P < 0.001), ischemic stroke (HR 3.02 [1.07-8.53], P = 0.04), and the composite of both (HR 2.42 [1.41-4.15], P < 0.001).

Conclusions: In patients with HF advanced IAB predicts new-onset AF and ischemic stroke. Future studies must assess whether anticoagulant treatment in Bayes' Syndrome leads to better outcomes in HF.
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http://dx.doi.org/10.1016/j.ijcard.2018.05.050DOI Listing
November 2018

Predictive biomarkers for death and rehospitalization in comorbid frail elderly heart failure patients.

BMC Geriatr 2018 05 9;18(1):109. Epub 2018 May 9.

Servei de Cardiologia i Unitat d'Insuficiència Cardíaca, Hospital Universitari Germans Trias i Pujol, Badalona, Barcelona, Spain.

Background: Heart failure (HF) is associated with a high rate of readmissions within 30 days post-discharge and in the following year, especially in frail elderly patients. Biomarker data are scarce in this high-risk population. This study assessed the value of early post-discharge circulating levels of ST2, NT-proBNP, CA125, and hs-TnI for predicting 30-day and 1-year outcomes in comorbid frail elderly patients with HF with mainly preserved ejection fraction (HFpEF).

Methods: Blood samples were obtained at the first visit shortly after discharge (4.9 ± 2 days). The primary endpoint was the composite of all-cause mortality or HF-related rehospitalization at 30 days and at 1 year. All-cause mortality alone at one year was also a major endpoint. HF-related rehospitalizations alone were secondary end-points.

Results: From February 2014 to November 2016, 522 consecutive patients attending the STOP-HF Clinic were included (57.1% women, age 82 ± 8.7 years, mean Barthel index 70 ± 25, mean Charlson comorbidity index 5.6 ± 2.2). The composite endpoint occurred in 8.6% patients at 30 days and in 38.5% at 1 year. In multivariable analysis, ST2 [hazard ratio (HR) 1.53; 95% CI 1.19-1.97; p = 0.001] was the only predictive biomarker at 30 days; at 1 year, both ST2 (HR 1.34; 95% CI 1.15-1.56; p < 0.001) and NT-proBNP (HR 1.19; 95% CI 1.02-1.40; p = 0.03) remained significant. The addition of ST2 and NT-proBNP into a clinical predictive model increased the AUC from 0.70 to 0.75 at 30 days (p = 0.02) and from 0.71 to 0.74 at 1 year (p < 0.05). For all-cause death at 1 year, ST2 (HR 1.50; 95% CI 1.26-1.80; p < 0.001), and CA125 (HR 1.41; 95% CI 1.21-1.63; p < 0.001) remained independent predictors in multivariable analysis. The addition of ST2 and CA125 into a clinical predictive model increased the AUC from 0.74 to 0.78 (p = 0.03). For HF-related hospitalizations, ST2 was the only predictive biomarker in multivariable analyses, both at 30 days and at 1 year.

Conclusions: In a comorbid frail elderly population with HFpEF, ST2 outperformed NT-proBNP for predicting the risk of all-cause mortality or HF-related rehospitalization. ST2, a surrogate marker of inflammation and fibrosis, may be a better predictive marker in high-risk HFpEF.
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http://dx.doi.org/10.1186/s12877-018-0807-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5944009PMC
May 2018

Telomere attrition in heart failure: a flow-FISH longitudinal analysis of circulating monocytes.

J Transl Med 2018 02 20;16(1):35. Epub 2018 Feb 20.

Cardiology Service, Germans Trias i Pujol University Hospital, Carretera del Canyet s/n, 08916, Badalona, Spain.

Background: Cross-sectional investigations report shorter telomeres in patients with heart failure (HF); however, no studies describe telomere length (TL) trajectory and its relationship with HF progression. Here we aimed to investigate telomere shortening over time and its relationship to outcomes.

Methods: Our study cohort included 101 ambulatory patients with HF. Blood samples were collected at baseline (n = 101) and at the 1-year follow-up (n = 54). Using flow-FISH analysis of circulating monocytes, we simultaneously measured three monocyte subsets-classical (CD14CD16), intermediate (CD14CD16), and nonclassical (CD14CD16)-and their respective TLs based on FITC-labeled PNA probe hybridization. The primary endpoints were all-cause death and the composite of all-cause death or HF-related hospitalization, assessed at 2.3 ± 0.6 years. All statistical analyses were executed by using the SPSS 15.0 software, and included Student's t test and ANOVA with post hoc Scheffe analysis, Pearson or Spearman rho correlation and univariate Cox regression when applicable.

Results: We found high correlations between TL values of different monocyte subsets: CD14CD16 vs. CD14CD16, R = 0.95, p < 0.001; CD14CD16 vs. CD14CD16, R = 0.90, p < 0.001; and CD14CD16 vs. CD14CD16, R = 0.89, p < 0.001. Mean monocyte TL exhibited significant attrition from baseline to the 1-year follow-up (11.1 ± 3.3 vs. 8.3 ± 2.1, p < 0.001). TL did not significantly differ between monocyte subsets at either sampling time-point (all p values > 0.1). Cox regression analyses did not indicate that TL or ΔTL was associated with all-cause death or the composite endpoint.

Conclusions: Overall, this longitudinal study demonstrated a ~ 22% reduction of TL in monocytes from ambulatory patients with HF within 1 year. TL and ΔTL were not related to outcomes over long-term follow-up.
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http://dx.doi.org/10.1186/s12967-018-1412-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5819711PMC
February 2018

Bio-profiling and bio-prognostication of chronic heart failure with mid-range ejection fraction.

Int J Cardiol 2018 04 31;257:188-192. Epub 2018 Jan 31.

Heart Failure Clinic, Health Sciences Research Institute, Hospital Universitari Germans Trias i Pujol, Badalona, Spain; Department of Medicine, Universitat Autonoma de Barcelona, Barcelona, Spain; CIBERCV, Instituto de Salud Carlos III, Madrid, Spain. Electronic address:

Background: Recent ESC guidelines on heart failure (HF) have introduced a new phenotype based on left ventricular ejection fraction (LVEF), called the mid-range (HFmrEF). This phenotype falls between the classical reduced (HFrEF) and preserved (HFpEF) HF phenotypes. We aimed to characterize the HFmrEF biomarker profile and outcomes.

Methods: 1069 consecutive ambulatory patients were included in the study (age 66.2 ± 12.8 years); 800 with HFrEF (74.8%), 134 with HFmrEF (12.5%), and 135 with HFpEF (12.5%). We measured serum concentrations of N-terminal pro-brain natriuretic peptide (NT-proBNP), high-sensitivity troponin T (hs-TnT), soluble suppression of tumorigenicity (ST2), galectin-3, high-sensitivity C-reactive protein, cystatin-C, neprilysin, and soluble transferrin receptor, during 4.9 ± 2.8 years of follow-up. The primary end-point was the composite: cardiovascular death or HF-related hospitalization. We also examined all-cause, cardiovascular death, and the composite: all-cause death or HF-related hospitalization.

Results: NTproBNP levels in HFmrEF were similar to levels in HFpEF, but significantly lower than levels in HFrEF. No other studied biomarkers were different between HFmrEF and HFrEF. All biomarkers, except neprilysin, showed higher risk prediction capabilities in HFmrEF than in HFrEF or HFpEF. The largest difference between HFrEF and HFmrEF was the hs-TnT level (hazard ratio [HR]: 4.72, 95% CI: 2.81-7.94 vs. HR: 1.67, 95%CI: 1.74-1.89; all p < 0.001).

Conclusions: Although HFmrEF is acknowledged as an intermediate phenotype between HFrEF and HFpEF, from a multi-biomarker point of view, HFmrEF was similar to HFrEF, except that NTproBNP levels were lower. Biomarkers commonly used for HFrEF risk prediction are more valuable for HFmrEF risk stratification.
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http://dx.doi.org/10.1016/j.ijcard.2018.01.119DOI Listing
April 2018

Impact of a 'stent for life' initiative on post-ST elevation myocardial infarction heart failure: a 15 year heart failure clinic experience.

ESC Heart Fail 2018 02 29;5(1):101-105. Epub 2017 Dec 29.

Heart Institute, Hospital Universitari Germans Trias i Pujol, Badalona, Spain.

Aims: Multidisciplinary heart failure (HF) clinics are a cornerstone of contemporary HF management. The stent-for-life (SFL) initiative improves mortality after ST elevation myocardial infarction (STEMI), but its impact in post-STEMI HF is not well characterized. Here we assessed the impact of SFL among patients referred to a multidisciplinary HF clinic over a 15 year time period.

Methods And Results: Between 2001 and 2015, 1921 patients were admitted to our HF clinic. In 2009, Catalonia established the Codi IAM network, a regional STEMI network that prioritizes primary percutaneous coronary intervention in STEMI. Patients admitted during the study period were divided into two groups based on admission date: pre-SFL (2001-June 2009; n = 1031) and post-SFL (July 2009-2015; n = 890). Compared with those in the pre-SFL group, patients admitted in the post-SFL period had better New York Heart Association (NYHA) functional class (22.1 vs. 38.7 NYHA classes III-IV; P < 0.001) and higher left ventricular ejection fraction (LVEF) (36.1 ± 19.6 vs. 32.6 ± 13.4; P < 0.001). Among STEMI survivors, 101 (6.7%) pre-SFL patients and 40 (2%) post-SFL patients (P < 0.001) fulfilled the criteria for HF clinic referral (Killip-Kimball class ≥ 2 during index admission and/or LVEF of <40%). Furthermore, among patients admitted to the HF clinic, post-STEMI HF with reduced ejection fraction patients comprised 8.9% of the pre-SFL group and only 4.2% of the post-SFL group (P < 0.001).

Conclusions: Among patients treated at our multidisciplinary HF clinic, the adoption of an SFL network has decreased the prevalence of post-STEMI HF with reduced ejection fraction.
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http://dx.doi.org/10.1002/ehf2.12245DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5793981PMC
February 2018

Clinical characteristics, one-year change in ejection fraction and long-term outcomes in patients with heart failure with mid-range ejection fraction: a multicentre prospective observational study in Catalonia (Spain).

BMJ Open 2017 12 21;7(12):e018719. Epub 2017 Dec 21.

Heart Diseases Biomedical Research Group (GREC), IMIM (Hospital del Mar Medical Research Institute), Barcelona, Spain.

Objectives: The aim of this study was to analyse baseline characteristics and outcome of patients with heart failure and mid-range left ventricular ejection fraction (HFmrEF, left ventricular ejection fraction (LVEF) 40%-49%) and the effect of 1-year change in LVEF in this group.

Setting: Multicentre prospective observational study of ambulatory patients with HF followed up at four university hospitals with dedicated HF units.

Participants: Fourteen per cent (n=504) of the 3580 patients included had HFmrEF.

Interventions: Baseline characteristics, 1-year LVEF and outcomes were collected. All-cause death, HF hospitalisation and the composite end-point were the primary outcomes.

Results: Median follow-up was 3.66 (1.69-6.04) years. All-cause death, HF hospitalisation and the composite end-point were 47%, 35% and 59%, respectively. Outcomes were worse in HF with preserved ejection fraction (HFpEF) (LVEF>50%), without differences between HF with reduced ejection fraction (HFrEF) (LVEF<40%) and HFmrEF (all-cause mortality 52.6% vs 45.8% and 43.8%, respectively, P=0.001). After multivariable Cox regression analyses, no differences in all-cause death and the composite end-point were seen between the three groups. HF hospitalisation and cardiovascular death were not statistically different between patients with HFmrEF and HFrEF. At 1-year follow-up, 62% of patients with HFmrEF had LVEF measured: 24% had LVEF<40%, 43% maintained LVEF 40%-49% and 33% had LVEF>50%. While change in LVEF as continuous variable was not associated with better outcomes, those patients who evolved from HFmrEF to HFpEF did have a better outcome. Those who remained in the HFmrEF and HFrEF groups had higher all-cause mortality after adjustment for age, sex and baseline LVEF (HR 1.96 (95% CI 1.08 to 3.54, P=0.027) and HR 2.01 (95% CI 1.04 to 3.86, P=0.037), respectively).

Conclusions: Patients with HFmrEF have a clinical profile in-between HFpEF and HFrEF, without differences in all-cause mortality and the composite end-point between the three groups. At 1 year, patients with HFmrEF exhibited the greatest variability in LVEF and this change was associated with survival.
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http://dx.doi.org/10.1136/bmjopen-2017-018719DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5778274PMC
December 2017

Prognostic value of circulating microRNAs on heart failure-related morbidity and mortality in two large diverse cohorts of general heart failure patients.

Eur J Heart Fail 2018 01 26;20(1):67-75. Epub 2017 Sep 26.

ACS Biomarker BV, Amsterdam, The Netherlands.

Aims: Small studies suggested circulating microRNAs (miRNAs) as biomarkers for heart failure (HF). However, standardized approaches and quality assessment for measuring circulating miRNAs are not uniformly established, and most studies have been small, so that results are inconsistent. We used a standardized data handling protocol, optimized for circulating miRNA qPCRs to remove noise and used it to assess which circulating miRNAs robustly add prognostic information in patients with HF.

Methods And Results: We measured 12 miRNAs in two independent cohorts totalling 2203 subjects. Cohort I (Barcelona) comprised 834 chronic HF patients. Cohort II (Detroit) comprised 1369 chronic HF patients. Each sample was measured in duplicate, and normalized to a very abundant and stable miRNA (miR-486-5p). We used a multistep algorithm to distinguish false amplification signals and thus classify each miRNA measurement as 'valid', 'undetectable' or 'invalid'. Higher levels of miR-1254 and miR-1306-5p were significantly associated with risk of the combined endpoint of all-cause mortality and HF hospitalization in both cohorts, with hazard ratios ranging from 1.11 to 1.21 per log increase (P-values 0.004 to 0.009). However, adding these miRNAs to established predictors (age, sex, haemoglobin, renal function, and NT-proBNP) did not further augment the c-statistic beyond 0.69 (cohort I) or 0.70 (cohort II).

Conclusion: We used a stringent quality assessment for miRNA testing, and were able to replicate the association of miR-1254 and miR-1306-5p with risk of death and HF hospitalization in HF patients of two independent cohorts. However, these two circulating miRNAs failed to improve prognostication over established predictors.
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http://dx.doi.org/10.1002/ejhf.984DOI Listing
January 2018

Recovered heart failure with reduced ejection fraction and outcomes: a prospective study.

Eur J Heart Fail 2017 12 6;19(12):1615-1623. Epub 2017 Apr 6.

Heart Failure Unit, Hospital Universitari Germans Trias i Pujol, Badalona, Barcelona, Spain.

Aims: Significant recovery of left ventricular ejection fraction (LVEF) occurs in a proportion of patients with heart failure (HF) and reduced ejection fraction (HFrEF). We analysed outcomes, including mortality [all-cause, cardiovascular (CV), HF-related, and sudden death], and HF-related hospitalizations in this HF-recovered group. The primary endpoint was a composite of CV death or HF hospitalization.

Methods And Results: LVEF was assessed at baseline and at 1 year in 1057 consecutive HF patients. Patients were classified into three groups: (i) HF-recovered: LVEF <45% at baseline and ≥45% at 1 year (n = 233); (ii) HF with preserved EF (HFpEF): LVEF ≥45% throughout follow-up (n = 117); and (iii) HFrEF: LVEF <45% throughout follow-up (n = 707). Mean follow-up was 5.6 ± 3.1 years. HF-recovered patients differed from HFrEF and HFpEF groups in demographic and clinical characteristics. The mean LVEF increase was 21.1 ± 10 points in HF-recovered patients. Using the HF-recovered group as a reference, the risks for the primary composite endpoint (n = 376), with non-CV death as competing risk, for HFpEF and HFrEF groups were: hazard ratio (HR) 2.33 [95% confidence interval (CI) 1.60-3.39], P < 0.001 and HR 1.99 (95% CI 1.50-2.65), P < 0.001, respectively. All-cause (n = 429), CV (n = 245), HF-related (n = 127), and sudden death (n = 60) were significantly lower in HF-recovered subjects relative to HFrEF (all P < 0.01). HF-recovered patients also experienced less recurrent HF hospitalizations (P < 0.001).

Conclusion: One in four treated patients with HFrEF showed recovery of systolic function. HF-recovered patients had significantly improved mortality and morbidity relative to HFpEF and HFrEF subjects. Further research is needed to identify optimal medications and device indications for HF-recovered patients.
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http://dx.doi.org/10.1002/ejhf.824DOI Listing
December 2017

Bloodstream Amyloid-beta (1-40) Peptide, Cognition, and Outcomes in Heart Failure.

Rev Esp Cardiol (Engl Ed) 2017 Nov 6;70(11):924-932. Epub 2017 Mar 6.

Unidad de Insuficiencia Cardiaca, Servicio de Cardiología, Hospital Universitari Germans Trias i Pujol, Badalona, Barcelona, Spain; Departamento de Medicina, Universidad Autónoma de Medicina, Barcelona, Spain; CIBERCV (CB16/11/00403), Instituto de Salud Carlos III, Madrid, Spain.

Introduction And Objectives: In the brain, amyloid-beta generation participates in the pathophysiology of cognitive disorders; in the bloodstream, the role of amyloid-beta is uncertain but may be linked to sterile inflammation and senescence. We explored the relationship between blood levels of amyloid-beta 1-40 peptide (Aβ40), cognition, and mortality (all-cause, cardiovascular, and heart failure [HF]-related) in ambulatory patients with HF.

Methods: Bloodstream Aβ40 was measured in 939 consecutive patients with HF. Cognition was evaluated with the Pfeiffer questionnaire (adjusted for educational level) at baseline and during follow-up. Multivariate Cox regression analyses and measurements of performance (discrimination, calibration, and reclassification) were used, with competing risk for specific causes of death.

Results: Over 5.1 ± 2.9 years, 471 patients died (all-cause): 250 from cardiovascular causes and 131 HF-related. The median Aβ40 concentration was 519.1 pg/mL [Q1-Q3: 361.8-749.9 pg/mL]. The Aβ40 concentration correlated with age, body mass index, renal dysfunction, and New York Heart Association functional class (all P < .001). There were no differences in Aβ40 in patients with and without cognitive impairment at baseline (P = .97) or during follow-up (P = .20). In multivariable analysis, including relevant clinical predictors and N-terminal pro-B-type natriuretic peptide, Aβ40 remained significantly associated with all-cause death (HR, 1.22; 95%CI, 1.10-1.35; P < .001) and cardiovascular death (HR, 1.18; 95%CI, 1.03-1.36; P = .02), but not with HF-related death (HR, 1.13; 95%CI, 0.93-1.37; P = .22). Circulating Aβ40 improved calibration and patient reclassification.

Conclusions: Blood levels of Aβ40 are not associated with cognitive decline in HF. Circulating Aβ40 was predictive of mortality and may indicate systemic aging.
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http://dx.doi.org/10.1016/j.rec.2017.02.021DOI Listing
November 2017

Early Postdischarge STOP-HF-Clinic Reduces 30-day Readmissions in Old and Frail Patients With Heart Failure.

Rev Esp Cardiol (Engl Ed) 2017 Aug 16;70(8):631-638. Epub 2017 Feb 16.

Departament de Medicina, Universitat Autònoma de Barcelona, Barcelona, Spain; Servei de Cardiologia-Unitat d'IC, Hospital Universitari Germans Trias i Pujol, Badalona, Barcelona, Spain; CIBER-CV (CB16/11/00403), Instituto de Salud Carlos III, Madrid, Spain. Electronic address:

Introduction And Objectives: Heart failure (HF) is associated with a high rate of readmissions within 30 days postdischarge. Strategies to lower readmission rates generally show modest results. To reduce readmission rates, we developed a STructured multidisciplinary outpatient clinic for Old and frail Postdischarge patients hospitalized for HF (STOP-HF-Clinic).

Methods: This prospective all-comers study enrolled patients discharged from internal medicine or geriatric wards after HF hospitalization. The intervention involved a face-to-face early visit (within 7 days), HF nurse education, treatment titration, and intravenous medication when needed. Thirty-day readmission risk was calculated using the CORE-HF risk score. We also studied the impact of 30-day readmission burden on regional health care by comparing the readmission rate in the STOP-HF-Clinic Referral Area (∼250000 people) with that of the rest of the Catalan Health Service (CatSalut) (∼7.5 million people) during the pre-STOP-HF-Clinic (2012-2013) and post-STOP-HF-Clinic (2014-2015) time periods.

Results: From February 2014 to June 2016, 518 consecutive patients were included (age, 82 years; Barthel score, 70; Charlson index, 5.6, CORE-HF 30-day readmission risk, 26.5%). The observed all-cause 30-day readmission rate was 13.9% (47.5% relative risk reduction) and the observed HF-related 30-day readmission rate was 7.5%. The CatSalut registry included 65131 index HF admissions, with 9267 all-cause and 6686 HF-related 30-day readmissions. The 30-day readmission rate was significantly reduced in the STOP-HF-Clinic Referral Area in 2014-2015 compared with 2012-2013 (P < .001), mainly driven by fewer HF-related readmissions.

Conclusions: The STOP-HF-Clinic, an approach that could be promptly implemented elsewhere, is a valuable intervention for reducing the global burden of early readmissions among elder and vulnerable patients with HF.
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http://dx.doi.org/10.1016/j.rec.2017.01.003DOI Listing
August 2017