Trajectories of chronic multimorbidity patterns in older patients: MTOP study.

BACKGROUND: Multimorbidity is associated with negative results and poses difficulties in clinical management. New methodological approaches are emerging based on the hypothesis that chronic conditions are non-randomly associated forming multimorbidity patterns. However, there are few longitudinal studies of these patterns, which could allow for better preventive strategies and healthcare planning. The objective of the MTOP (Multimorbidity Trajectories in Older Patients) study is to identify patterns of chronic multimorbidity in a cohort of older patients and their progression and trajectories in the previous 10 years. METHODS: A retrospective, observational study with a cohort of 3988 patients aged > 65 was conducted, including suspected and confirmed COVID-19 patients in the reference area of Parc Taulí University Hospital. Real-world data on socio-demographic and diagnostic variables were retrieved. Multimorbidity patterns of chronic conditions were identified with fuzzy c-means cluster analysis. Trajectories of each patient were established along three time points (baseline, 5 years before, 10 years before). Descriptive statistics were performed together with a stratification by sex and age group. RESULTS: 3988 patients aged over 65 were included (58.9% females). Patients with ≥ 2 chronic conditions changed from 73.6 to 98.3% in the 10-year range of the study. Six clusters of chronic multimorbidity were identified 10 years before baseline, whereas five clusters were identified at both 5 years before and at baseline. Three clusters were consistently identified in all time points (Metabolic and vascular disease, Musculoskeletal and chronic pain syndrome, Unspecific); three clusters were only present at the earliest time point (Male-predominant diseases, Minor conditions and sensory impairment, Lipid metabolism disorders) and two clusters emerged 5 years before baseline and remained (Heart diseases and Neurocognitive). Sex and age stratification showed different distribution in cluster prevalence and trajectories. CONCLUSIONS: In a cohort of older patients, we were able to identify multimorbidity patterns of chronic conditions and describe their individual trajectories in the previous 10 years. Our results suggest that taking these trajectories into consideration might improve decisions in clinical management and healthcare planning. TRIAL REGISTRATION NUMBER: NCT05717309.

Factors related to early readmissions after acute heart failure: a nested case-control study.

AIMS: To describe the main characteristics of patients who were readmitted to hospital within 1 month after an index episode for acute decompensated heart failure (ADHF). METHODS AND RESULTS: This is a nested case-control study in the ReIC cohort, cases being consecutive patients readmitted after hospitalization for an episode of ADHF and matched controls selected from those who were not readmitted. We collected clinical data and also patient-reported outcome measures, including dyspnea, Minnesota Living with Heart Failure Questionnaire (MLHFQ), Tilburg Frailty Indicator (TFI) and Hospital Anxiety and Depression Scale scores, as well as symptoms during a transition period of 1 month after discharge. We created a multivariable conditional logistic regression model. Despite cases consulted more than controls, there were no statistically significant differences in changes in treatment during this first month. Patients with chronic decompensated heart failure were 2.25 [1.25, 4.05] more likely to be readmitted than de novo patients. Previous diagnosis of arrhythmia and time since diagnosis ≥ 3 years, worsening in dyspnea, and changes in MLWHF and TFI scores were significant in the final model. CONCLUSION: We present a model with explanatory variables for readmission in the short term for ADHF. Our study shows that in addition to variables classically related to readmission, there are others related to the presence of residual congestion, quality of life and frailty that are determining factors for readmission for heart failure in the first month after discharge. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03300791. First registration: 03/10/2017.

Benefit of Neoral C2 monitoring in de novo cardiac transplant recipients receiving basiliximab induction.

BACKGROUND: For cyclosporine (CsA), 2-hr postdose level (C2) is the best single time point predictor of the area under the curve and a critical measure for effective dosing. The therapeutic CsA microemulsion (Neoral) C2 range in de novo heart transplant patients remains to be determined. PURPOSE: The purpose of this study was to determine the efficacy of CsA C2 monitoring in de novo heart transplant patients receiving basiliximab induction. METHODS: This prospective, multicenter, randomized study enrolled 87 adult heart transplant recipients stratified according to 4 to 6 hrs posttransplant serum creatinine less than or equal to 170 micromol/L (cohort A) or more than 170 micromol/L (cohort B). Patients in cohort A were randomized into three C2 ranges (A1: "high" n=25, 1600-1800 ng/mL; A2: "intermediate" n=27, 1400-1600 ng/mL; and A3: "low" n=24, 1200-1400 ng/mL). Patients in cohort B were randomized into intermediate (n=5) and low C2 (n=6). Target ranges were progressively lowered after 1 month. Immunosuppression included basiliximab, Neoral, mycophenolate mofetil, and corticosteroids. Endpoints were acute rejection and renal function. RESULTS: The incidence of acute rejection at 12 months was 44% in group A1, 41% in group A2, 33% in group A3, and 27% in cohort B. Pretransplant and 12-month creatinine clearance (mL/min) were group A1, 72+/-25 and 64+/-24; group A2, 81+/-32 and 68+/-25; group A3, 91+/-28 and 86+/-26; and cohort B, 62+/-28 and 79+/-37. CONCLUSION: These results suggest that C2 monitoring is safe in de novo heart transplant patients. A low Neoral C2 range in combination with basiliximab induction resulted in preserved renal function without increased risk of acute rejection.

[Treatment of atrial fibrillation at different levels of health care]. / Tratamiento de la fibrilación auricular en los distintos niveles asistenciales de un área sanitaria.

BACKGROUND AND OBJECTIVE: Atrial fibrillation is managed in multiple settings by different specialists. We sought to analyze treatment and compliance of the prevailing guidelines of patients with atrial fibrillation attended at different levels of health care and to quantify interventions to correct treatment inadequacies. PATIENTS AND METHOD: We included all adult patients with atrial fibrillation who presented during a 14 day-period to different levels of health care of a tertiary hospital and a related primary care clinic (family physician, cardiologist, emergency department, hospitalization). In all of them, clinical and epidemiological data in relation to atrial fibrillation, and all data referring to treatment and compliance of guidelines, were recorded prospectively. RESULTS: 293 patients were included. Clinical and epidemiological data were similar in the different settings. A great diversity in atrial fibrillation treatment was observed. In 30 and 33% of the patients, antiarrhythmic and antithrombotic treatment, respectively, did not meet the recommendations of the prevailing guidelines. The adequacy was inferior in primary care. The adequacy percentages increased slightly after the medical attention (2 and 3% respectively, p non significant) with no differences in this increase between the different settings. CONCLUSIONS: There are no epidemiological differences between patients with atrial fibrillation treated at different levels of health care. An important number of patients do not follow the recommendations of the prevailing guidelines. There is a clear medical abstention in incorrectly treated cases.

[Impaired endothelium-dependent forearm vasodilation in idiopathic dilated cardiomyopathy is related to severe left ventricular dysfunction and elevated serum tumor necrosis factor levels]. / La disfunción endotelial periférica en la miocardiopatía dilatada idiopática se asocia con mayor disfunción ventricular y concentraciones plasmáticas elevadas de factor de necrosis tumoral.

INTRODUCTION AND OBJECTIVES: Endothelial dysfunction has been found in patients with idiopathic dilated cardiomyopathy (IDC), but its mechanism remains unknown. Our aim was to investigate whether forearm endothelium-dependent vasoreactivity correlates with cardiac disease severity or neurohormonal activation. PATIENTS AND METHOD: We studied 23 patients with IDC and 10 healthy sex- and age-matched controls using brachial artery ultrasound to assess flow-mediated dilation (FMD) and nitroglycerin-induced vasodilation (NIV). In the IDC group, we determined plasma neurohormone and cytokine levels at the same time. RESULTS: FMD was significantly less in the IDC group compared with the control group [--0.06 (2.8)% vs 4.4 (4.6)%, respectively; P<.01], whereas NIV was similar in both groups [15.0 (6.4)% vs 14.0 (7.4)%, respectively; P=NS]. FMD was significantly less in patients with poorer left ventricular (LV) function and more severe LV dilatation, and in those with a higher tumor necrosis factor-alpha (TNF-alpha) level. NIV was similar in all patient subgroups. There was a significant inverse correlation between the TNF-alpha plasma level and FMD (r=-0.75; P<.01). No correlation was found between the plasma levels of other neurohormones and FMD. CONCLUSIONS: FMD, but not NIV, was impaired in patients with IDC compared with control subjects. In patients, there were significant associations between FMD impairment and the severity of LV dilatation, the severity of LV systolic dysfunction, and the plasma TNF-alpha level. The strongest correlation was observed between TNF-alpha plasma level and FMD. These data suggest that TNF-alpha may be implicated in endothelial dysfunction in patients with IDC.

[Prognostic value of cytokines and neurohormones in severe heart failure]. / Valor pronóstico de los niveles de citocinas y neurohormonas en la insuficiencia cardíaca severa.

BACKGROUND AND OBJECTIVES: The screening of candidates for heart transplantation continues to present difficulties. High plasma levels of cytokines and neurohormones have been associated with a poor prognosis in heart failure but their usefulness for identifying candidates for heart transplantation is still not established. METHODS: In 83 patients (59 11 years old), with systolic left ventricular dysfunction and New York Heart Association functional class III-IV, we assessed levels of aldosterone, atrial natriuretic peptide, plasma renin activity, angiotensin II, norepinephrine, endothelin, interleukin-6 and tumor necrosis factor-alpha. RESULTS: Over the following year, 13 patients died and 26 received heart transplantation. Mean ejection fraction was 23 6%, end-diastolic and end-systolic diameters were 73 10 and 60 10 mm, respectively. Univariate analysis identified the following variables to be associated with poor prognosis: angiotensin II (p = 0.001), norepinephrine (p = 0.003), plasma renin activity (p = 0.02), systolic blood pressure (p = 0.006), end-diastolic diameter (p = 0.02) and end-systolic diameter (p = 0.04). Multivariate regression analysis identified the following variables to be independent predictors of death or need for heart transplantation: a low cardiac index (p = 0.007), plasma angiotensin II (p = 0.001) and pulmonary capillary wedge pressure (p = 0.04) The sensitivity and specificity of angiotensin II for predicting poor outcome was only moderate according to interpretation of the receiver operating curves. CONCLUSIONS: Although plasma angiotensin II was the best neurohormone for identifying patients with severe heart failure and the worst prognosis, its sensitivity and specificity for predicting death or the need for heart transplantation was limited. The decision to transplant should continue to be based on clinical and hemodynamic parameters.

Increased expression of the renin-angiotensin system and mast cell density but not of angiotensin-converting enzyme II in late stages of human heart failure.

BACKGROUND: The activation of the renin-angiotensin system (RAS) contributes to the progression of left ventricular dysfunction. A novel human homologue of the angiotensin-converting enzyme (ACE), named ACE2, has been described but its role in human heart failure (HF) has not been elucidated. Besides, there is controversy as to whether the major angiotensin II-forming-activity in heart is ACE or chymase released from mast cells. Furthermore, long-term blockade of nitric oxide (NO) synthesis has been shown to increase ACE activity. To assess the locally activated vasoactive mediators that may contribute to the ventricular deterioration process, we sought to simultaneously analyze their expression in failing hearts. METHODS: We analyzed left ventricular biopsies from 30 patients with heart failure undergoing heart transplantation and 12 organ donors. The mRNA levels of ACE, ACE2, chymase and endothelial nitric oxide synthase (eNOS), were quantified by real-time polymerase chain reaction and mast cell density was assessed by immunohistochemistry. The mRNA levels of the atrial natriuretic peptide (ANP) and the brain natriuretic peptide (BNP) were also quantified as controls. RESULTS: There was higher ACE and chymase mRNA expression and mast cell density in failing than in control myocardium and no changes in ACE2 expression were detected. eNOS mRNA levels were lower in failing hearts. Both ANP and BNP expression were higher in pathological than in control samples. CONCLUSIONS: These data document a decompensation of vasoactive systems that may contribute to the progressive impairment of the myocardial function in HF. On the other hand, ACE2 mRNA expression is not altered in human end-stage HF.

Epitope mapping of mitochondrial adenine nucleotide translocase-1 in idiopathic dilated cardiomyopathy.

Mitochondrial adenine nucleotide translocase (ANT) is a specific target for the autoantibody response in idiopathic dilated cardiomyopathy (IDCM). We have undertaken an epitope analysis of ANT in IDCM by immunoblot with recombinant GST-ANT fusion proteins and with cellulose-bound decapeptides of human ANT1. Forty-five patients with IDCM, 17 patients with ischemic left ventricle dysfunction (LVD) and 20 controls were analyzed for circulating antibodies against ANT (AAb-ANT). Sixteen of the 45 (36%) IDCM patients showed AAb-ANT above controls. In immunoblots, AAb-ANT detected purified bovine heart ANT and GST-ANT1 and GST-ANT2 isoforms and, less frequently, the GST-ANT3 isoform. A construct lacking the last 146 amino acids did not react with AAb-ANT, indicating that the main epitopes are in the C-terminal 146 amino acids. Immunodetection of decapeptides covering this region shows that AAb-ANT detects at least three epitopes, demonstrating that ANT is the primary target of AAb-ANT. The most significant epitopes belong to the M2 and M3 hydrophilic loops of ANT suggesting that apart from being essential for its activity, these loops are highly immunogenic.