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Background: Limited data are available on the long-term trajectory of estimated glomerular filtration rate (eGFR) in patients with chronic heart failure., Objectives: The authors evaluated eGFR dynamics using the 2009 Chronic Kidney Disease Epidemiology Collaboration equation and its prognostic significance in a real-world cohort over a 15-year follow-up., Methods: A prospective observational registry of ambulatory heart failure outpatients was conducted, with regular eGFR assessments at baseline and on a 3-month schedule for ≤15 years. Urgent kidney function assessments were excluded. Locally weighted error sum of squares curves were plotted for predefined subgroups. Multivariable longitudinal Cox regression analyses were conducted to assess associations with all-cause and cardiovascular death., Results: A total of 2,672 patients were enrolled consecutively between August 2001 and December 2021. The average age was 66.8 ± 12.6 years, and 69.8% were men. Among 40,970 creatinine measurements, 28,634 were used for eGFR analysis, averaging 10.7 ± 8.5 per patient. Over the study period, a significant decline in eGFR was observed in the entire cohort, with a slope of -1.70 mL/min/1.73 m 2 per year (95% CI: -1.75 to -1.66 mL/min/1.73 m 2 per year). Older patients, those with diabetes, a preserved ejection fraction, a higher baseline eGFR, elevated hospitalization rates, and those who died during follow-up experienced more pronounced decreases in the eGFR. Moreover, the decrease in kidney function correlated independently with all-cause mortality and cardiovascular death., Conclusions: These findings highlight the sustained decline in eGFR over 15 years in patients with heart failure, with variations based on clinical characteristics, and emphasize the importance of regular eGFR monitoring in this population., Competing Interests: Funding Support and Author Disclosures Dr Bayes-Genis has lectured or participated in advisory boards for Abbott, AstraZeneca, Boehringer-Ingelheim, Bayer, Novartis, Roche Diagnostics, and Vifor. Dr Nuñez has received personal fees or advisory boards from Alleviant, AstraZeneca, Boehringer Ingelheim, Bayer, Novartis, NovoNordisk, Rovi, and Vifor CSL. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2024 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: The prediction of sudden cardiac death (SCD) in heart failure (HF) remains an unmet need. The aim of our study was to assess the prevalence of SCD over 20 years in outpatients with HF managed in a Mediterranean multidisciplinary HF Clinic, and to compare the proportion of SCD (SCD/all-cause death) to the expected proportional occurrence based on the validated Seattle Proportional Risk Model (SPRM) score., Methods and Results: This prospective observational registry study included 2772 outpatients with HF admitted between August 2001 and May 2021. Patients were included when the cause of death was known and SPRM score was available. Over the 20-year study period, 1351 patients (48.7%) died during a median follow-up period of 3.8 years (interquartile range 1.6-7.6). Among these patients, the proportion of SCD out of the total of deaths was 13.6%, whereas the predicted by SPRM was 39.6%. This lower proportion of SCD was observed independently of left ventricular ejection fraction, ischemic etiology, and the presence of an implantable cardiac defibrillator., Conclusions: In a Mediterranean cohort of outpatients with HF, the proportion of SCD was lower than expected based on the SPRM score. Future studies should investigate to what extend epidemiological and guideline-directed medical therapy patterns influence SCD., Competing Interests: Declaration of Competing Interest A.B.-G. received speaker fees from Novartis. J.N. received speaker fees from Novartis, Vifor Pharma, Boehringer Ingelheim, Astra Zeneca, Rovi, and Novonordisk. P.C. and E. S. received speaker fees from Novartis. A.B.-G. and J.L. report a relationship with Critical Diagnostics. W.L. is in the steering committee for Respircardia and Cardiac Dimensions, clinical event committees for Abbott, EBR Systems, Beckman Coulter (NTproBNP), and Siemens (NTproBNP). He has a grant support from Medtronic and is a consultant to Medtronic and Impulse Dynamics. University of Washington holds the copyright to the SPRM., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Objectives: To describe the characteristics of safety alerts issued by the Spanish Medicines Agency (AEMPS) and the Spanish Pharmacovigilance System over a 7-year period and the regulatory actions they generated. Methods: A retrospective analysis was carried out of drug safety alerts published on the AEMPS website from 1 January 2013 to 31 December 2019. Alerts that were not drug-related or were addressed to patients rather than healthcare professionals were excluded. Results: During the study period, 126 safety alerts were issued, 12 of which were excluded because they were not related to drugs or were addressed to patients and 22 others were excluded as they were duplications of previous alerts. The remaining 92 alerts reported 147 adverse drug reactions (ADRs) involving 84 drugs. The most frequent source of information triggering a safety alert was spontaneous reporting (32.6%). Four alerts (4.3%) specifically addressed health issues related to children. ADRs were considered serious in 85.9% of the alerts. The most frequent ADRs were hepatitis (seven alerts) and congenital malformations (five alerts), and the most frequent drug classes were antineoplastic and immunomodulating agents (23%). Regarding the drugs involved, 22 (26.2%) were "under additional monitoring." Regulatory actions induced changes in the Summary of Product Characteristics in 44.6% of alerts, and in eight cases (8.7%), the alert led to withdrawal from the market of medicines with an unfavorable benefit/risk ratio. Conclusion: This study provides an overview of drug safety alerts issued by the Spanish Medicines Agency over a 7-year period and highlights the contribution of spontaneous reporting of ADRs and the need to assess safety throughout the lifecycle of medicines., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Montané and Santesmases.)

Background: The impact of increasing temperatures on renal function in heart failure (HF) outpatients has never been specifically analyzed., Methods: We retrieved creatinine and estimated glomerular filtration rate (eGFR) values of all HF outpatients followed at a HF clinic and temperature data from 2002 to 2021. For each patient and each year we averaged values of creatinine, eGFR and monthly temperatures during summer and the rest of the year., Results: The study cohort included 2167 HF patients undergoing 25,865 elective visits, with a median of 14 visits for each patient (interquartile range 7-23). At the first visit, patients (70% men) had an age of 67 ± 13 years, and a left ventricular ejection fraction of 35 ± 14%. Creatinine was 1.25 ± 0.51 mg/dL, and eGFR was 65 ± 25 mL/min/1.73 m 2 . When pooling together all average values of creatinine and eGFR measured during summer or in the rest of the year, creatinine was significantly higher in summer (difference 0.04, 95% confidence interval [CI] 0.04 to 0.05, p < 0.001), and eGFR was slightly lower (difference - 2.0, 95% CI -2.3 to -1.8, p < 0.001). Temperature rise during summer increased from 2002 to 2021. The absolute (Δ) and percent (Δ%) elevation in temperature during summer displayed independent associations with Δ and Δ% creatinine and eGFR after adjusting for age, sex, plasma creatinine, and HF therapies., Conclusions: The magnitude of temperature elevation during summer has increased over 20 years. This elevation correlates with the decline in renal function during summer. This might be an example of how global warming is affecting human health., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Aims: Prior 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 Results: This 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 with sacubitril/valsartan treatment (ARNI ON), and a 6 week period of sacubitril/valsartan withdrawal (ARNI OFF). The primary endpoint was change in mPAP with and without sacubitril/valsartan. Secondary endpoints included changes in 6 min walking distance, B-line sum in lung ultrasound, and quality of life (QoL). During the study period, 1717 mPAP measurements were recorded. Between pre-ARNI vs. ARNI ON, mPAP significantly declined by -4.99 mmHg [95% confidence interval (CI) -5.55 to -4.43]. Between ARNI ON vs. ARNI OFF, mPAP significantly increased by +2.84 mmHg [95% CI +2.26 to +3.42]. Between pre-ARNI vs. ARNI ON, we found an improvement in 6 min walking distance, B-lines, and QoL. Mean loop diuretic management did not differ between periods., Conclusions: Sacubitril/valsartan significantly reduced mPAP in patients with HFpEF-PH, independent of loop diuretic management, together with improvement in functional capacity, lung congestion, and QoL. Sacubitril/valsartan may be a therapeutic alternative in HFpEF-PH., (© 2022 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Objectives: Heart failure (HF) management has significantly improved over the past two decades, leading to better survival. This study aimed to assess changes in predicted mortality risk after 12 months of management in a multidisciplinary HF clinic., Materials and Methods: Out of 1,032 consecutive HF outpatients admitted from March-2012 to November-2018, 357 completed the 12-months follow-up and had N-terminal pro-B-type natriuretic peptide (NTproBNP), high sensitivity troponin T (hs-TnT), and interleukin-1 receptor-like-1 (known as ST2) measurements available both at baseline and follow-up. Three contemporary risk scores were used: MAGGIC-HF, Seattle HF Model (SHFM), and the Barcelona Bio-HF (BCN Bio-HF) calculator, which incorporates the three above mentioned biomarkers. The predicted risk of all-cause death at 1 and 3 years was calculated at baseline and re-evaluated after 12 months., Results: A significant decline in predicted 1-and 3-year mortality risk was observed at 12 months: MAGGIC ~16%, SHFM ~22% and BCN Bio-HF ~15%. In the HF with reduced ejection fraction (HFrEF) subgroup guideline-directed medical therapy led to a complete normalization of left ventricular ejection fraction (≥50%) in almost a third of the patients and to a partial normalization (41-49%) in 30% of them. Repeated risk assessment after 12 months with SHFM and BCN Bio-HF provided adequate discrimination for all-cause 3-year mortality (C-Index: MAGGIC-HF 0.762, SHFM 0.781 and BCN Bio-HF 0.791)., Conclusion: Mortality risk declines in patients with HF managed for 12 months in a multidisciplinary HF clinic. Repeating the mortality risk assessment after optimizing the HF treatment is recommended, particularly in the HFrEF subgroup., Competing Interests: AB-G has received lecture honoraria from Abbott, AstraZeneca, Boehringer-Ingelheim, Novartis, Vifor, Roche Diagnostics, and Critical Diagnostics. AB-G and JL report a relationship with Critical Diagnostics. WL—steering committee for Respircardia and Cardiac Dimensions, clinical event committees for Abbott, EBR Systems, Beckman Coulter NTproBNP, and Siemens NTproBNP. He has grant support from Medtronic. He is a consultant to Medtronic and Impulse Dynamics. University of Washington CoMotion holds the copyright to the SHFM. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Codina, Zamora, Levy, Revuelta-López, Borrellas, Spitaleri, Cediel, Ruiz-Cueto, Cañedo, Santiago-Vacas, Domingo, Buchaca, Subirana, Santesmases, Espriella, Nuñez, Lupón and Bayes-Genis.)

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.

Aims: Several heart failure (HF) web-based risk scores are currently used in clinical practice. Currently, we lack head-to-head comparison of the accuracy of risk scores. This study aimed to assess correlation and mortality prediction performance of Meta-Analysis Global Group in Chronic Heart Failure (MAGGIC-HF) risk score, which includes clinical variables + medications; Seattle Heart Failure Model (SHFM), which includes clinical variables + treatments + analytes; PARADIGM Risk of Events and Death in the Contemporary Treatment of Heart Failure (PREDICT-HF) and Barcelona Bio-Heart Failure (BCN-Bio-HF) risk calculator, which also include biomarkers, like N-terminal pro B-type natriuretic peptide (NT-proBNP)., Methods and Results: A total of 1166 consecutive patients with HF from different aetiologies that had NT-proBNP measurement at first visit were included. Discrimination for all-cause mortality was compared by Harrell's C-statistic from 1 to 5 years, when possible. Calibration was assessed by calibration plots and Hosmer-Lemeshow test and global performance by Nagelkerke's R 2 . Correlation between scores was assessed by Spearman rank test. Correlation between the scores was relatively poor (rho value from 0.66 to 0.79). Discrimination analyses showed better results for 1-year mortality than for longer follow-up (SHFM 0.817, MAGGIC-HF 0.801, PREDICT-HF 0.799, BCN-Bio-HF 0.830). MAGGIC-HF showed the best calibration, BCN-Bio-HF overestimated risk while SHFM and PREDICT-HF underestimated it. BCN-Bio-HF provided the best discrimination and overall performance at every time-point., Conclusions: None of the contemporary risk scores examined showed a clear superiority over the rest. BCN-Bio-HF calculator provided the best discrimination and overall performance with overestimation of risk. MAGGIC-HF showed the best calibration, and SHFM and PREDICT-HF tended to underestimate risk. Regular updating and recalibration of online web calculators seems necessary to improve their accuracy as HF management evolves at unprecedented pace., (© 2021 The Authors. European Journal of Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

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., (Copyright © 2020 Sociedad Española de Cardiología. Published by Elsevier España, S.L.U. All rights reserved.)

Background: Circulating Neprilysin (sNEP) has emerged as a potential prognostic biomarker in heart failure (HF). In PARAGON-HF benefit of sacubitril/valsartan was only observed in patients with left ventricular ejection fraction (LVEF) ≤57%. We aimed to assess the prognostic value of sNEP in outpatients with HF and LVEF >57%, in comparison with patients with LVEF ≤57%., Methods: Consecutive HF outpatients were included from May-2006 to February-2016. The primary endpoint was the composite of all-cause death or HF hospitalization and the main secondary endpoint was the composite of cardiovascular death or HF hospitalization. For the later competing risk methods were used., Results: sNEP was measured in 1428 patients (age 67.7±12.7, 70.3% men, LVEF 35.8% ±14), 144 of which had a LVEF >57%. sNEP levels did not significantly differ between LVEF groups (p = 0.31). During a mean follow-up of 6±3.9 years, the primary endpoint occurred in 979 patients and the secondary composite endpoint in 714 (in 111 and 84 of the 144 patients with LVEF >57%, respectively). sNEP was significantly associated with both composite endpoints. Age- and sex- adjusted Cox regression analyses showed higher hazard ratios for sNEP in patients with LVEF >57%, both for the primary (HR 1.37 [1.16-1.61] vs. 1.04 [0.97-1.11]) and the secondary (HR 1.38 [1.21-1.55] vs. 1.11 [1.04-1.18]) composite endpoints., Conclusions: sNEP prognostic value in patients with HF and LVEF >57% outperforms that observed in patients with lower LVEF. Precision medicine using sNEP may identify HF patients with preserved LVEF that may benefit from treatment with sacubitril/valsartan., Competing Interests: A. Bayes-Genis has received speaker fees from Novartis; Julio Núñez has received speaker fees from Novartis, Vifor Pharma, Boehringer Ingelheim, Astra Zeneca, Rovi, and Novonordisk; A. Bayes-Genis and J. Lupón have applied for a patent for sNEP as prognostic biomarker and report a relationship with Critical Diagnostics. The rest of the authors have no conflicts of interest. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

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.

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., (© 2020 European Society of Cardiology.)

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.

An adverse drug reaction (ADR) is defined as a response to a medicinal product which is noxious and unintended. ADRs are an important cause of morbidity and mortality and increase health costs. The pharmacovigilance systems allow the identification and prevention of the risks associated with use of a drug, especially of recently marketed drugs; they detect signals from data of the global ADR register and also support decisions taken by regulatory agencies in different countries. Only a few drugs are withdrawn from the market, mainly due to hepatotoxicity. Spontaneous notification of ADR is the cheapest, simplest and most used method to recognize new safety drug problems, under-reporting being its main limitation. The future of pharmacovigilance and ADRs will include a higher involvement of patients, doctors, health authorities and pharmaceutical companies, and the use of new technologies., (Copyright © 2019 Elsevier España, S.L.U. All rights reserved.)

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., (Copyright © 2019 Elsevier B.V. All rights reserved.)

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., (© 2019 The Authors. European Journal of Heart Failure © 2019 European Society of Cardiology.)

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.

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., (Copyright © 2018 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

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.

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, P <.001, and 36.5±20.7, P =.003, respectively). No statistically significant differences in fragility between HFmrEF (48.6%) and HFrEF (41.9%) ( P =.09) nor HFpEF (54.3%) ( P =.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 ( P ≤.001), and fragility was independently associated with all-cause death and the composite end point ( P <.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.

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., (Copyright © 2018 Elsevier B.V. All rights reserved.)

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., (© 2017 The Authors. European Journal of Heart Failure © 2017 European Society of Cardiology.)

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., (Copyright © 2017 Sociedad Española de Cardiología. Published by Elsevier España, S.L.U. All rights reserved.)

Background: Patients with diabetes mellitus (DM) have an increased risk of developing heart failure (HF). Further, DM is associated with poor prognosis in patients with HF. Our aim was to determine whether DM has any impact on the predictive value of a multi-biomarker panel in patients with HF., Methods: We included 1069 consecutive ambulatory HF patients in the study: age 66.2 ± 12.8 years, 33.5 ± 13.3 left ventricular ejection fraction, 36% diabetic patients. We measured serum concentrations of N-terminal pro-brain natriuretic peptide (NT-proBNP), high-sensitivity troponin T (hs-TnT), ST2, galectin-3, high-sensitivity C reactive protein (hs-CRP), cystatin-C, soluble transferrin receptor (sTfR), and neprilysin and followed patients for 4.9 ± 2.8 years. Primary endpoints were all-cause and cardiovascular death., Results: During follow-up, 534 patients died; 283 died of cardiovascular causes. Diabetic subjects had higher mortality (57.7 vs. 45.6%, p < 0.001). NTproBNP (p = 0.07), hs-TnT (p < 0.001), galectin-3 (p < 0.001), and cystatin-C (p = 0.001) concentrations were higher in diabetic patients, whereas sTfR levels were lower (p = 0.005). There were no interactions between DM and NTproBNP, hs-TnT, galectin-3, hs-CRP, cystatin-C, sTfR, and neprilysin relative to risk prediction for all-cause or cardiovascular death. By contrast, ST2 significantly interacted with DM for all-cause (p = 0.02) and cardiovascular (p = 0.03) death. In diabetic patients, HRs for ST2 were 1.27 (95% CI 1.16-1.40, p < 0.001) and 1.23 (95% CI 1.09-1.39, p = 0.001) for all-cause and cardiovascular death, respectively. In nondiabetic patients, HRs for ST2 were 1.53 (95% CI 1.35-1.73, p < 0.001) and 1.64 (95% CI 1.31-2.05, p < 0.001) for all-cause and cardiovascular death, respectively. The multivariable Cox regression analysis showed that hs-TnT and ST2 were the only markers that were independently associated with both all-cause and cardiovascular mortality in patients with HF and diabetes. Moreover, in these patients, the combination of these two markers significantly increased discrimination as assessed by the area under the curve., Conclusions: Biomarkers used in the general population to predict the clinical course of heart failure are also useful in patients with diabetes. In these patients, among all the biomarkers analysed only hs-TnT and ST2 were independently associated with both all-cause and cardiovascular mortality.

Introduction and Objectives: The influence of hemoglobin kinetics on outcomes in heart failure has been incompletely established., Methods: Hemoglobin was determined at the first visit and at 6 months. Anemia was defined according to World Health Organization criteria (hemoglobin < 13g/dL for men and hemoglobin < 12g/dL for women). Patients were classified relative to their hemoglobin values as nonanemic (both measurements normal), transiently anemic (anemic at the first visit but not at 6 months), newly anemic (nonanemic initially but anemic at 6 months), or permanently anemic (anemic in both measurements)., Results: A total of 1173 consecutive patients (71.9% men, mean age 66.8±12.2 years) were included in the study. In all, 476 patients (40.6%) were considered nonanemic, 170 (14.5%) had transient anemia, 147 (12.5%) developed new-onset anemia, and 380 (32.4%) were persistently anemic. During a follow-up of 3.7±2.8 years after the 6-month visit, 494 patients died. On comprehensive multivariable analyses, anemia (P < .001) and the type of anemia (P < .001) remained as independent predictors of all-cause mortality. Compared with patients without anemia, patients with persistent anemia (hazard ratio [HR] = 1.62; 95% confidence interval [95%CI], 1.30-2.03; P < .001) and new-onset anemia (HR = 1.39; 95%CI, 1.04-1.87, P = .03) had higher mortality, and even transient anemia showed a similar trend, although without reaching statistical significance (HR = 1.31; 95%CI, 0.97-1.77, P = .075)., Conclusions: Anemia, especially persistent and of new-onset, and to a lesser degree, transient anemia, is deleterious in heart failure., (Copyright © 2016 Sociedad Española de Cardiología. Published by Elsevier España, S.L.U. All rights reserved.)

Aims: Paradoxically, obesity is associated with survival in heart failure (HF). Whether this is true for HF patients with comorbid type-2 diabetes (T2D) remains uncertain. Our aim was to address this issue in diabetic patients by collecting correlates for body mass index (BMI) and long-term mortality., Method and Results: Both BMI and survival after a mean follow-up of 4.3 ± 3.0 years (up to 10 years) were assessed for 2527 ambulatory patients (66.3% men; mean age 69 ± 12.3 years). A total of 1102 (43.6%) patients had T2D and ischaemic aetiology of HF was present in 47.8%; mean left ventricular ejection fraction was 38 ± 16%. Based on BMI scores, patients were categorized as either underweight, normal, overweight, or obese. A significant survival interaction was observed between BMI and T2D. Smooth spline curves for the estimation of risk of all-cause and cardiovascular death showed the classic obesity paradox, with reduced mortality as BMI increased in non-diabetics; for T2D patients this pattern was lost. After adjustment for age and sex, hazard ratios for low-weight and obesity were: 2.04 [95% confidence intervals (CI) 1.50-2.78, P < 0.001] and 0.76 (95% CI 0.58-0.99, P = 0.04), respectively, for non-T2D patients; and 1.30 (95% CI 0.77-2.19, P = 0.32) and 0.99 (95% CI 0.78-1.26, P = 0.95), respectively, for T2D patients. Multivariate analyses for mortality (including BMI as a continuous variable) were significant for non-diabetic patients only., Conclusions: In patients with HF, but without T2D, the obesity paradox was present; however, T2D removed this phenomenon. Advice about weight loss for obese diabetic patients with HF requires further research., (© 2016 The Authors. European Journal of Heart Failure © 2016 European Society of Cardiology.)

Background: In heart failure (HF), weight loss (WL) has been associated with an adverse prognosis whereas obesity has been linked to lower mortality (the obesity paradox). The impact of WL in obese patients with HF is incompletely understood. Our objective was to explore the prevalence of WL and its impact on long-term mortality, with an emphasis on obese patients, in a cohort of patients with chronic HF., Methods and Results: Weight at first visit and the 1-year follow-up and vital status after 3 years were assessed in 1000 consecutive ambulatory, chronic HF patients (72.7% men; mean age 65.8±12.1 years). Significant WL was defined as a loss of ≥5% weight between baseline and 1 year. Obesity was defined as body mass index ≥30 kg/m(2) (N=272). Of the 1000 patients included, 170 experienced significant WL during the first year of follow-up. Mortality was significantly higher in patients with significant WL (27.6% versus 15.3%, P<0.001). In univariable Cox regression analysis, patients with significant WL had 2-fold higher mortality (hazard ratio 1.95 [95% CI 1.39-2.72], P<0.001). In multivariable analysis, adjusting for age, sex, body mass index, New York Heart Association functional class, left ventricular ejection fraction, HF duration, ischemic etiology, diabetes, and treatment, significant WL remained independently associated with higher mortality (hazard ratio 1.89 [95% CI 1.32-2.68], P<0.001). Among obese patients with HF, significant WL was associated with an even more ominous prognosis (adjusted hazard ratio for death of 2.38 [95% CI 1.31-4.32], P=0.004) than that observed in nonobese patients (adjusted hazard ratio 1.83 [95% CI 1.16-2.89], P=0.01)., Conclusions: Weight loss ≥5% in patients with chronic HF was associated with high long-term mortality, particularly among obese patients with HF., (© 2016 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.)

Objective: To assess the relationship between resting heart rate and long-term all-cause mortality in ambulatory patients with heart failure (HF) relative to age, considering that although heart rate has been strongly associated with mortality in HF, the influence of age on target heart rate is incompletely characterized., Patients and Methods: Consecutive patients in sinus rhythm referred to an ambulatory HF clinic of a university hospital between August 1, 2001, and March 31, 2012, were included. Unadjusted and adjusted Cox regression analyses were performed to assess heart rate as a prognostic marker, both as a continuous variable and after categorization into quintiles. Smooth spline estimates and hazard ratios (HRs) were plotted for 2 age strata (<75 years vs ≥75 years) for each individual heart rate., Results: A total of 1033 patients were included (766 men [74.2%]; mean age, 65.1±12.6 years). During a mean follow-up of 4.6±3.3 years (median, 3.8 years [25th-75th percentile, 1.9-6.9]), 476 patients (46.1%) died. Mortality was associated with a statistically greater heart rate in the total cohort (HR, 1.18; 95% CI, 1.11-1.26; P<.001). From a clinical viewpoint, this means an 18% increased risk for every 10-beats/min elevation in heart rate. The same characteristics were present in the relationship between heart rate assessed after 6 months and long-term mortality (HR, 1.30; 95% CI, 1.20-1.42; P<.001). Overall, the prognostic importance of heart rate in ambulatory patients with HF was largely influenced by patient age. Remarkably, in the elderly population (≥75 years), heart rate below 68 beats/min conferred an increased risk of death, whereas in younger patients, mortality exhibited a declining slope at even the lowest heart rates., Conclusion: Our research, if applicable to the prospective management of patients with ambulatory HF, suggests that patients aged 75 years or older have the best outcomes with target heart rates of 68 beats/min; however, younger patients may benefit from lower heart rates, even below 55 beats/min., (Copyright © 2015 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc. All rights reserved.)

Objectives: To characterize trends from 1987 to 2001 in the prevalence of HIV and HCV infections among 2219 injection drug users (IDUs) starting treatment for substance abuse in two large hospitals in metropolitan Barcelona., Methods: The study population comprised IDUs with HIV tests completed from 1987 to 2001 and admitted for detoxification. Testing for HCV started in 1991 (n=1132). Characterization of temporal trends was carried out using logistic regression methods. Stratification was used to describe possible heterogeneities of the temporal trends., Results: The overall prevalence of HIV, HCV, and HBV (HBsAg+) was 55%, 88%, and 7%, respectively. Adjusted by duration of IDU, sex, and age at initiation, the prevalence of HIV infection declined significantly (p<0.001) from 1989 to 2004. The substantially higher prevalence of HCV showed a decline (p=0.065) of lesser magnitude. The decline of HIV infection was consistently observed among those with duration of IDU of less than 10 years. In turn, the decline of HCV was restricted to those with short duration of IDU (<4 years) because the prevalence of HCV infection was close to 100% for durations longer than 4 years in all calendar periods., Conclusions: Preventive interventions and treatment for substance abuse might have contributed to the waning of the HIV epidemic in Spain. However, the extremely high levels of HCV infection and the underlying prevalence of HIV might lead to a large health burden of liver disease.