A Prospective Observational Study of Frailty in Geriatric Revitalization Aimed at Community-Dwelling Elderly.

(1) Background: The increasing life expectancy brings an increase in geriatric syndromes, specifically frailty. The literature shows that exercise is a key to preventing, or even reversing, frailty in community-dwelling populations. The main objective is to demonstrate how an intervention based on multicomponent exercise produces an improvement in frailty and pre-frailty in a community-dwelling population. (2) Methods: a prospective observational study of a multicomponent exercise program for geriatric revitalization with people aged over 65 holding Barthel Index scores equal to, or beyond, 90. The program was developed over 30 weeks, three times a week, in sessions lasting 45-50 min each. Frailty levels were registered by the Short Physical Performance Battery, FRAIL Questionnaire Screening Tool, and Timed "Up & Go" at the beginning of the program, 30 weeks later (at the end of the program), and following 13 weeks without training; (3) Results: 360 participants completed the program; a greater risk of frailty was found before the program started among older women living in urban areas, with a more elevated fat percentage, more baseline pathologies, and wider baseline medication use. Furthermore, heterogeneous results were observed both in training periods and in periods without physical activity. However, they are consistent over time and show improvement after training. They show a good correlation between TUG and SPPB; (4) Conclusions: A thirty-week multicomponent exercise program improves frailty and pre-frailty status in a community-dwelling population with no functional decline. Nevertheless, a lack of homogeneity is evident among the various tools used for measuring frailty over training periods and inactivity periods.

Transcriptomic Analysis of Extracellular Vesicles in the Search for Novel Plasma and Thrombus Biomarkers of Ischemic Stroke Etiologies.

Accurate etiologic diagnosis provides an appropriate secondary prevention and better prognosis in ischemic stroke (IS) patients; still, 45% of IS are cryptogenic, urging us to enhance diagnostic precision. We have studied the transcriptomic content of plasma extracellular vesicles (EVs) (n = 21) to identify potential biomarkers of IS etiologies. The proteins encoded by the selected genes were measured in the sera of IS patients (n = 114) and in hypertensive patients with (n = 78) and without atrial fibrillation (AF) (n = 20). IGFBP-2, the most promising candidate, was studied using immunohistochemistry in the IS thrombi (n = 23) and atrium of AF patients (n = 13). In vitro, the IGFBP-2 blockade was analyzed using thromboelastometry and endothelial cell cultures. We identified 745 differentially expressed genes among EVs of cardioembolic, atherothrombotic, and ESUS groups. From these, IGFBP-2 (cutoff > 247.6 ng/mL) emerged as a potential circulating biomarker of embolic IS [OR = 8.70 (1.84-41.13) p = 0.003], which was increased in patients with AF vs. controls (p < 0.001) and was augmented in cardioembolic vs. atherothrombotic thrombi (p < 0.01). Ex vivo, the blockage of IGFBP-2 reduced clot firmness (p < 0.01) and lysis time (p < 0.001) and in vitro, diminished endothelial permeability (p < 0.05) and transmigration (p = 0.06). IGFBP-2 could be a biomarker of embolic IS and a new therapeutic target involved in clot formation and endothelial dysfunction.

Is the Combination of Robot-Assisted Therapy and Transcranial Direct Current Stimulation Useful for Upper Limb Motor Recovery? A Systematic Review with Meta-Analysis.

Stroke is the third leading cause of disability in the world, and effective rehabilitation is needed to improve lost functionality post-stroke. In this regard, robot-assisted therapy (RAT) and transcranial direct current stimulation (tDCS) are promising rehabilitative approaches that have been shown to be effective in motor recovery. In the past decade, they have been combined to study whether their combination produces adjuvant and greater effects on stroke recovery. The aim of this study was to estimate the effectiveness of the combined use of RATs and tDCS in the motor recovery of the upper extremities after stroke. After reviewing 227 studies, we included nine randomised clinical trials (RCTs) in this study. We analysed the methodological quality of all nine RCTs in the meta-analysis. The analysed outcomes were deficit severity, hand dexterity, spasticity, and activity. The addition of tDCS to RAT produced a negligible additional benefit on the effects of upper limb function (SMD -0.09, 95% CI -0.31 to 0.12), hand dexterity (SMD 0.12, 95% CI -0.22 to 0.46), spasticity (SMD 0.04, 95% CI -0.24 to 0.32), and activity (SMD 0.66, 95% CI -1.82 to 3.14). There is no evidence of an additional effect when adding tDCS to RAT for upper limb recovery after stroke. Combining tDCS with RAT does not improve upper limb motor function, spasticity, and/or hand dexterity. Future research should focus on the use of RAT protocols in which the patient is given an active role, focusing on the intensity and dosage, and determining how certain variables influence the success of RAT.

Combining transcranial direct current stimulation with hand robotic rehabilitation in chronic stroke patients: a double blind randomized clinical trial.

OBJECTIVE: This study aimed to assess the impact of combining transcranial direct current stimulation (tDCS) with end-effector robot-assisted treatment (RAT) on upper limb function, spasticity, and hand dexterity in chronic stroke patients. DESIGN: This was a prospective, double-blind randomized trial with 20 equally allocated stroke patients. The experimental group received dual-tDCS (anode over affected M1, cathode over contralateral M1) alongside RAT, while the control group received sham tDCS with the same electrode placement + RAT. Each patient underwent 20 combined tDCS and RAT sessions. The primary outcome measure was the Fugl Meyer Upper Limb motor score (mFM-UL), with secondary outcomes including AMADEO® kinematic measures, Action Research Arm Test (ARAT), and Functional Independence Measure (FIM). Assessments were conducted at baseline, post-rehabilitation, and three months later. RESULTS: Combining bilateral tDCS with RAT did not yield additional improvements in mFM-UL, FIM, or ARAT scores among stroke patients. However, the real tDCS group showed enhanced finger flexion in the affected hand based on AMADEO® kinematic measures. CONCLUSION: The addition of tDCS to RAT did not result in significant overall functional improvements in chronic stroke patients. However, a benefit was observed in finger flexion of the affected hand.

Myocardial Interstitial Fibrosis in Hypertensive Heart Disease: From Mechanisms to Clinical Management.

Hypertensive heart disease (HHD) can no longer be considered as the beneficial adaptive result of the hypertrophy of cardiomyocytes in response to pressure overload leading to the development of left ventricular hypertrophy. The current evidence indicates that in patients with HHD, pathological lesions in the myocardium lead to maladaptive structural remodeling and subsequent alterations in cardiac function, electrical activity, and perfusion, all contributing to poor outcomes. Diffuse myocardial interstitial fibrosis is probably the most critically involved lesion in these disorders. Therefore, in this review, we will focus on the histological characteristics, the mechanisms, and the clinical consequences of myocardial interstitial fibrosis in patients with HHD. In addition, we will consider the most useful tools for the noninvasive diagnosis of myocardial interstitial fibrosis in patients with HHD, as well as the most effective available therapeutic strategies to prevent its development or facilitate its regression in this patient population. Finally, we will issue a call to action for the need for more fundamental and clinical research on myocardial interstitial fibrosis in HHD.

Multifactorial Causation of Alzheimer's Disease Due to COVID-19.

There are several implications of the surge in the incidence of pandemics and epidemics in the last decades. COVID-19 being the most remarkable one, showed the vulnerability of patients with neurodegenerative diseases like Alzheimer's disease (AD). This review studies the pathological interlinks and triggering factors between the two illnesses and proposes a multifactorial pathway of AD causation due to COVID-19. The article evaluates and describes all the postulated hypotheses which explain the etiology and possible pathogenesis of the disease in four domains: Inflammation & Neurobiochemical interactions, Oxidative Stress, Genetic Factors, and Social Isolation. We believe that a probable hypothesis of an underlying cause of AD after COVID-19 infection could be the interplay of all these factors.

Clinical outcome prediction of acute neurological patients admitted to the emergency department: Sequential Organ Failure Assessment score and modified SOFA score.

Background: The aim of this study was to determine the ability of the Sequential Organ Failure Assessment score (SOFA) and modified SOFA score (mSOFA) as predictive tools for 2-day and 28-day mortality and ICU admission in patients with acute neurological pathology treated in hospital emergency departments (EDs). Methods: An observational, prospective cohort study in adults with acute neurological disease transferred by ambulance to an ED was conducted from 1 January 2019 to 31 August 2022 in five hospitals in Castilla-León (Spain). Score discrimination was assessed by the area under the curve (AUC) of the receiver operating characteristic (ROC) curve of the score. Results: A total of 640 adult patients with neurological disease were included. For the prediction of 2-day mortality (all-cause), mSOFA presented a higher AUC than SOFA (mSOFA = 0.925 vs. SOFA = 0.902). This was not the case for 28-day mortality, for which SOFA was higher than mSOFA (mSOFA = 0.852 vs. SOFA = 0.875). Finally, ICU admission showed that SOFA was higher than mSOFA (mSOFA = 0.834 vs. SOFA = 0.845). Conclusion: Both mSOFA and SOFA presented similar predictive ability, with mSOFA being the best predictor for short-term mortality and SOFA being the best predictor for medium-term mortality, as well as for ICU admission. These results in a cohort of patients with acute neurological pathology pave the way for the use of both predictive tools in the ED. The inclusion of these tools could improve the clinical assessment and further treatment of neurological patients, who commonly present the worst outcomes.

A randomized, double-blind study on the efficacy of oral domperidone versus placebo for reducing SARS-CoV-2 viral load in mild-to-moderate COVID-19 patients in primary health care.

INTRODUCTION: The clinical effect of domperidone against COVID-19 has been investigated in a double-blind phase III clinical trial (EudraCT number 2021-001228-17). Domperidone has shown in vitro antiviral activity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and potential immudolatory properties through the stimulation of prolactin secretion. PATIENTS AND METHODS: The efficacy of oral domperidone plus standard of care (SOC; n = 87) versus placebo plus SOC (n = 86) was evaluated in a 28-day randomized double-blind multicentre study in primary health care centres. A total of 173 outpatients with mild-to-moderate COVID-19 were included. Three daily doses of 10 mg (30 mg/day) of domperidone or placebo were administered for 7 days. Reduction of viral load on day 4 was the primary efficay endpoint. It was estimated in saliva samples by reverse transcription-quantitative polymerase chain reaction (RT-qPCR), as the cycle thresholds detected ORF1ab, N Protein and S Protein genes. RESULTS: A significant reduction in the viral load was observed (p < 0.001) from baseline to days 4, 7 and 14 of the three genes studied with non-significant differences between domperidone and placebo groups. Twenty-three patients (13.3%) experienced adverse events, 14 patients in the domperidone group (16.1%) and 9 patients in the placebo group (10.5%). No patients needed to be hospitalized. CONCLUSION: Results do not prove the use of domperidone as antiviral in patients with COVID-19.

A 28-day double-blind clinical trial was performed to investigate the antiviral effect of domperidone, 30 mg/day for 7 days (n = 87) versus placebo (n = 86) in outpatients with mild-to-moderate COVID-19.The primary efficacy endpoint was the reduction of viral load on day 4 as compared with baseline, estimated as the cycle thresholds to detect ORF1ab, N Protein and S Protein genes by RT-qPCR in saliva samples.The study findings do not prove the use of domperidone as antiviral in patients with COVID-19.

Transition of patients with metabolic bone disease from paediatric to adult healthcare services: current situation and proposals for improvement.

BACKGROUND: There are currently no models for the transition of patients with metabolic bone diseases (MBDs) from paediatric to adult care. The aim of this project was to analyse information on the experience of physicians in the transition of these patients in Spain, and to draw up consensus recommendations with the specialists involved in their treatment and follow-up. METHODS: The project was carried out by a group of experts in MBDs and included a systematic review of the literature for the identification of critical points in the transition process. This was used to develop a questionnaire with a total of 48 questions that would determine the degree of consensus on: (a) the rationale for a transition programme and the optimal time for the patient to start the transition process; (b) transition models and plans; (c) the information that should be specified in the transition plan; and (d) the documentation to be created and the training required. Recommendations and a practical algorithm were developed using the findings. The project was endorsed by eight scientific societies. RESULTS: A total of 86 physicians from 53 Spanish hospitals participated. Consensus was reached on 45 of the 48 statements. There was no agreement that the age of 12 years was an appropriate and feasible point at which to initiate the transition in patients with MBD, nor that a gradual transition model could reasonably be implemented in their own hospital. According to the participants, the main barriers for successful transition in Spain today are lack of resources and lack of coordination between paediatric and adult units. CONCLUSIONS: The TEAM Project gives an overview of the transition of paediatric MBD patients to adult care in Spain and provides practical recommendations for its implementation.

Foot morphology as a predictor of hallux valgus development in children.

An excess of body weight can produce morphological changes in the feet of children. The aim of this study was to assess the morphological differences of the foot in children based on their body mass index and to determine the risk factors for the development of a hallux valgus in childhood and adolescence. One Thousand Six Hundred Seventy-Eight children (5-17 years) were classified as group with obesity, overweight, and normal weight. Lengths, widths, heights and angles of both feet was measured with a 3D scanner. The risk of developing hallux valgus was calculated. Group with overweight and obesity presented longer feet (p = 0.00), wider metatarsals (p = 0.00) and wider heels (p = 0.00). Arch height was lower (p > 0.01) in the group with obesity, and the hallux angle was greater in the group with normal weight (p < 0.05). The relative risk of a lateral hallux deviation increases with age, foot length and heel width (Exp (B) > 1). Children with overweight and obesity had longer and wider feet. The arch height was higher in children with overweight, and lower in children with obesity. Age, foot length, and heel width could be risk factors for the development of hallux valgus, while metatarsal width and arch height could be protective factors. Monitorization of the development and characterization of the foot in childhood as a clinical tool could help professionals to early identify the patients presenting risk factors and prevent future deformities and other biomechanical conditions in adulthood by implementing protecting measures.

Long-Term Mortality in Patients Transferred by Emergency Medical Services: Prospective Cohort Study.

OBJECTIVE: This study aimed to determine the long-term mortality (one-year follow-up) associated with patients transferred by Emergency Medical Services (EMS), and to reveal the determinants (causes and risk factors). METHODS: This was a multicenter, prospective, observational, controlled, ambulance-based study of adult patients transferred by ambulance to emergency departments (EDs) from October 2019 through July 2021 for any cause. A total of six Advanced Life Support (ALS) units, 38 Basic Life Support (BLS) units, and five hospitals from Spain were included. Physiological, biochemical, demographic, and reasons for transfer variables were collected. A longitudinal analysis was performed to determine the factors associated to long-term mortality (any cause). RESULTS: The final cohort included 1,406 patients. The one-year mortality rate was 21.6% (n = 304). Mortality over the first two days reached 5.2% of all the patients; between Day 2 and Day 30, reached 5.3%; and between Day 31 and Day 365, reached 11.1%. Low Glasgow values, elevated lactate levels, elevated blood urea nitrogen (BUN) levels, low oxygen saturation, high respiratory rate, as well as being old and suffering from circulatory diseases and neurological diseases were risk factors for long-term mortality. CONCLUSION: The quick identification of patients at risk of long-term worsening could provide an opportunity to customize care through specific follow-up.

Cardiac Fibrosis in heart failure: Focus on non-invasive diagnosis and emerging therapeutic strategies.

Heart failure is a leading cause of mortality and hospitalization worldwide. Cardiac fibrosis, resulting from the excessive deposition of collagen fibers, is a common feature across the spectrum of conditions converging in heart failure. Eventually, either reparative or reactive in nature, in the long-term cardiac fibrosis contributes to heart failure development and progression and is associated with poor clinical outcomes. Despite this, specific cardiac antifibrotic therapies are lacking, making cardiac fibrosis an urgent unmet medical need. In this context, a better patient phenotyping is needed to characterize the heterogenous features of cardiac fibrosis to advance toward its personalized management. In this review, we will describe the different phenotypes associated with cardiac fibrosis in heart failure and we will focus on the potential usefulness of imaging techniques and circulating biomarkers for the non-invasive characterization and phenotyping of this condition and for tracking its clinical impact. We will also recapitulate the cardiac antifibrotic effects of existing heart failure and non-heart failure drugs and we will discuss potential strategies under preclinical development targeting the activation of cardiac fibroblasts at different levels, as well as targeting additional extracardiac processes.

Prehospital seizures: Short-term outcomes and risk stratification based in point-of-care testing.

BACKGROUND: Information for treatment or hospital derivation of prehospital seizures is limited, impairing patient condition and hindering patients risk assessment by the emergency medical services (EMS). This study aimed to determine the associated factors to clinical impairment, and secondarily, to determine risk factors associated to cumulative in-hospital mortality at 2, 7 and 30 days, in patients presenting prehospital seizures. METHODS: Prospective, multicentre, EMS-delivery study involving adult subjects with prehospital seizures, including five advanced life support units, 27 basic life support units and four emergency departments in Spain. All bedside variables: including demographic, standard vital signs, prehospital laboratory tests and presence of intoxication or traumatic brain injury (TBI), were analysed to construct a risk model using binary logistic regression and internal validation methods. RESULTS: A total of 517 patients were considered. Clinical impairment was present in 14.9%, and cumulative in-hospital mortality at 2, 7 and 30-days was 3.4%, 4.6% and 7.7%, respectively. The model for the clinical impairment indicated that respiratory rate, partial pressure of carbon dioxide, blood urea nitrogen, associated TBI or stroke were risk factors; higher Glasgow Coma Scale (GCS) scores mean a lower risk of impairment. Age, potassium, glucose, prehospital use of mechanical ventilation and concomitant stroke were risk factors associated to mortality; and oxygen saturation, a high score in GCS and haemoglobin were protective factors. CONCLUSION: Our study shows that prehospital variables could reflect the clinical impairment and mortality of patients suffering from seizures. The incorporation of such variables in the prehospital decision-making process could improve patient outcomes.

Can specific virtual reality combined with conventional rehabilitation improve poststroke hand motor function? A randomized clinical trial.

TRIAL OBJECTIVE: To verify whether conventional rehabilitation combined with specific virtual reality is more effective than conventional therapy alone in restoring hand motor function and muscle tone after stroke. TRIAL DESIGN: This prospective single-blind randomized controlled trial compared conventional rehabilitation based on physiotherapy and occupational therapy (control group) with the combination of conventional rehabilitation and specific virtual reality technology (experimental group). Participants were allocated to these groups in a ratio of 1:1. The conventional rehabilitation therapists were blinded to the study, but neither the participants nor the therapist who applied the virtual reality-based therapy could be blinded to the intervention. PARTICIPANTS: Forty-six patients (43 of whom completed the intervention period and follow-up evaluation) were recruited from the Neurology and Rehabilitation units of the Hospital General Universitario of Talavera de la Reina, Spain. INTERVENTION: Each participant completed 15 treatment sessions lasting 150 min/session; the sessions took place five consecutive days/week over the course of three weeks. The experimental group received conventional upper-limb strength and motor training (100 min/session) combined with specific virtual reality technology devices (50 min/session); the control group received only conventional training (150 min/session). RESULTS: As measured by the Ashworth Scale, a decrease in wrist muscle tone was observed in both groups (control and experimental), with a notably larger decrease in the experimental group (baseline mean/postintervention mean: 1.22/0.39; difference between baseline and follow-up: 0.78; 95% confidence interval: 0.38-1.18; effect size = 0.206). Fugl-Meyer Assessment scores were observed to increase in both groups, with a notably larger increase in the experimental group (total motor function: effect size = 0.300; mean: - 35.5; 95% confidence interval: - 38.9 to - 32.0; wrist: effect size = 0.290; mean: - 5.6; 95% confidence interval: - 6.4 to - 4.8; hand: effect size = 0.299; mean: - -8.9; 95% confidence interval: - 10.1 to - 7.6). On the Action Research Arm Test, the experimental group quadrupled its score after the combined intervention (effect size = 0.321; mean: - 32.8; 95% confidence interval: - 40.1 to - 25.5). CONCLUSION: The outcomes of the study suggest that conventional rehabilitation combined with a specific virtual reality technology system can be more effective than conventional programs alone in improving hand motor function and voluntary movement and in normalizing muscle tone in subacute stroke patients. With combined treatment, hand and wrist functionality and motion increase; resistance to movement (spasticity) decreases and remains at a reduced level. TRIALS REGISTRY: International Clinical Trials Registry Platform: ISRCTN27760662 (15/06/2020; retrospectively registered).

Preliminary study of the increase in health science students' body mass index during the Christmas holidays.

OBJECTIVES: There is a trend toward an increase in body mass index (BMI) among adolescents over the course of the year. This increase in BMI is more pronounced during vacation periods, when healthy habits are relaxed due to the increase in number of social, family, and festive events, with summer being the period with the greatest increase. The objective of this study was to evaluate changes in weight during Christmas vacation. Changes in weight, BMI, and waist circumference were evaluated in association with adherence to the Mediterranean diet or a low-fat diet. METHODS: A total of 67 university students participated in this pilot study, 10 men (14.9%) and 57 women (85.1%), with a mean age of 20.37 y (±4.07 y). The first weigh-in was on the day before the start of vacation; there were two more during the vacation and a final one when students returned to the course. RESULTS: In general, a significant increase (P < 0.05) in body weight was found between the first measurement and the ensuing measurements during the holidays. The students with a high-fat diet presented with a more pronounced change in weight, with significant differences being found between weights 1 and 3 and between weights 1 and 4 (P < 0.05). CONCLUSIONS: The data show that students gained a significant amount of weight during the Christmas holidays. Although the weight gain was not alarming, it does point to the possibility of weight gain among young adults during vacation periods and may reflect what happens in other social strata.

Modified Rapid Emergency Medicine Score-Lactate (mREMS-L) performance to screen non-anticipated 30-day-related-mortality in emergency department.

BACKGROUND: The aim of this study was to compare the ability to predict 30-day in-hospital mortality of lactate versus the modified Rapid Emergency Medicine Score (mREMS) versus the arithmetic sum of the mREMS plus the numerical value of lactate (mREMS-L). METHODS: A prospective, multicentric, emergency department delivery, pragmatic study was conducted. To determine the predictive capacity of the scales, lactate was measured and the mREMS and mREMS-L were calculated in adult patients (aged>18 years) transferred with high priority by ambulance to the emergency department in five hospitals of Castilla y Leon between 1 January 2020 and 31 December 2021. The area under the receiver operating characteristic (ROC) curve of each of the scales was calculated in terms of mortality for 30 days. RESULTS: A total of 5371 participants were included, and the in-hospital mortality rate at 30 days was of 11.4% (615 cases). The best cut-off point determined in the mREMS was 7.0 points (sensitivity of 67% and specificity of 84%), and for lactate, the cut-off point was 1.4 mmol/L (sensitivity of 88% and specificity of 67%). Finally, the combined mREMS-L showed a cut-off point of 7.9 (sensitivity of 83% and a specificity of 83%). The area under the ROC curve of the mREMS, lactate and mREMS-L for 30-day mortality was 0.851, 0.853, and 0.903, respectively (p < 0.001 in all cases). CONCLUSIONS: The new score generated, mREMS-L, obtained better statistical results than its components (mREMS and lactate) separately.

Modified Sequential Organ Failure Assessment Score vs. Early Warning Scores in Prehospital Care to Predict Major Adverse Cardiac Events in Acute Cardiovascular Disease.

(1) Background: The Modified Sequential Organ Failure Assessment (mSOFA) is an Early Warning Score (EWS) that has proven to be useful in identifying patients at high risk of mortality in prehospital care. The main objective of this study was to evaluate the predictive validity of prehospital mSOFA in estimating 2- and 90-day mortality (all-cause) in patients with acute cardiovascular diseases (ACVD), and to compare this validity to that of four other widely-used EWS. (2) Methods: We conducted a prospective, observational, multicentric, ambulance-based study in adults with suspected ACVD who were transferred by ambulance to Emergency Departments (ED). The primary outcome was 2- and 90-day mortality (all-cause in- and out-hospital). The discriminative power of the predictive variable was assessed and evaluated by the area under the curve (AUC) of the receiver operating characteristic (ROC). (3) Results: A total of 1540 patients met the inclusion criteria. The 2- and 90-day mortality rates were 5.3% and 12.7%, respectively. The mSOFA showed the highest AUC of all the evaluated scores for both 2- and 90-day mortality, AUC = 0.943 (0.917-0.968) and AUC = 0.874 (0.847-0.902), respectively. (4) Conclusions: The mSOFA is a quick and easy-to-use EWS with an excellent ability to predict mortality at both 2 and 90 days in patients treated for ACVD, and has proved to be superior to the other EWS evaluated in this study.

Prediction of Left Ventricular Reverse Remodeling and Outcomes by Circulating Collagen-Derived Peptides.

BACKGROUND: Myocardial fibrosis may increase vulnerability to poor prognosis in patients with heart failure (HF), even in those patients exhibiting left ventricular reverse remodeling (LVRR) after guideline-based therapies. OBJECTIVES: This study sought to characterize fibrosis at baseline in patients with HF with left ventricular ejection fraction (LVEF) <50% by determining serum collagen type I-derived peptides (procollagen type I C-terminal propeptide [PICP] and ratio of collagen type I C-terminal telopeptide to matrix metalloproteinase-1) and to evaluate their association with LVRR and prognosis. METHODS: Peptides were determined in 1,034 patients with HF at baseline. One-year echocardiography was available in 665 patients. Associations of peptides with 1-year changes in echocardiographic variables were analyzed by multivariable linear mixed models. LVEF was considered improved if it increased by ≥15% or to ≥50% or if it increased by ≥10% to >40% in patients with LVEF ≤40%. Cardiovascular death and HF-related outcomes were analyzed in all patients randomized to derivation (n = 648) and validation (n = 386) cohorts. RESULTS: Continuous associations with echocardiographic changes were observed only for PICP. Compared with high-PICP (≥108.1 ng/mL) patients, low-PICP (<108.1 ng/mL) patients exhibited enhanced LVRR and a lower risk of HF-related outcomes (P ≤ 0.018), with women and nonischemic patients with HF showing a stronger LVEF increase (interaction P ≤ 0.010). LVEF increase was associated with a better prognosis, particularly in low-PICP patients (interaction P ≤ 0.029). Only patients with both low PICP and improved LVEF exhibited a better clinical evolution than patients with nonimproved LVEF (P < 0.001). CONCLUSIONS: Phenotyping with PICP, a peptide associated with myocardial fibrosis, may be useful to differentiate patients with HF who are more likely to experience clinical myocardial recovery from those with partial myocardial improvement.