Standardised Exercise Prescription for Patients with Chronic Coronary Syndrome and/or Heart Failure: A Consensus Statement from the EXPERT Working Group.

Whereas exercise training, as part of multidisciplinary rehabilitation, is a key component in the management of patients with chronic coronary syndrome (CCS) and/or congestive heart failure (CHF), physicians and exercise professionals disagree among themselves on the type and characteristics of the exercise to be prescribed to these patients, and the exercise prescriptions are not consistent with the international guidelines. This impacts the efficacy and quality of the intervention of rehabilitation. To overcome these barriers, a digital training and decision support system [i.e. EXercise Prescription in Everyday practice & Rehabilitative Training (EXPERT) tool], i.e. a stepwise aid to exercise prescription in patients with CCS and/or CHF, affected by concomitant risk factors and comorbidities, in the setting of multidisciplinary rehabilitation, was developed. The EXPERT working group members reviewed the literature and formulated exercise recommendations (exercise training intensity, frequency, volume, type, session and programme duration) and safety precautions for CCS and/or CHF (including heart transplantation). Also, highly prevalent comorbidities (e.g. peripheral arterial disease) or cardiac devices (e.g. pacemaker, implanted cardioverter defibrillator, left-ventricular assist device) were considered, as well as indications for the in-hospital phase (e.g. after coronary revascularisation or hospitalisation for CHF). The contributions of physical fitness, medications and adverse events during exercise testing were also considered. The EXPERT tool was developed on the basis of this evidence. In this paper, the exercise prescriptions for patients with CCS and/or CHF formulated for the EXPERT tool are presented. Finally, to demonstrate how the EXPERT tool proposes exercise prescriptions in patients with CCS and/or CHF with different combinations of CVD risk factors, three patient cases with solutions are presented.

Predictors of survival in patients undergoing cardiac rehabilitation after transcatheter aortic valve replacement (TAVR): a multicenter retrospective study.

BACKGROUND: The aim of this study was to evaluate cardiac rehabilitation (CR)-derived predictors of outcome in patients discharged from rehabilitation after transcatheter aortic valve replacement (TAVR). METHODS: We retrospectively analyzed data from 232 TAVR patients (aged 82±6 years, 55% females) discharged following an average 3-week residential CR program in the period January 2009 to December 2017. Comorbidities (cumulative illness rated state-comorbidity index, CIRS-CI), echocardiography on admission, disability (Barthel Index [BI]) and functional capacity (6-min walk distance, 6MWD) at discharge, and maximal training session intensity expressed in METs/min were collected. The endpoint was all-cause mortality. RESULTS: Seventy-four (32%) deaths occurred at 3-year follow-up. At discharge, non-survivors had a higher comorbidity rate (CIRS-CI 5.2±2.3 vs. 4.1±1.9, P=0.000), higher disability level (BI 80.4±24 vs. 88.8±17, P=0.000), and worse renal function (creatinine 1.6±0.9 vs. 1.2±0.4 mg/dL, P=0.000). They were also more often on diuretics (73% vs. 53.2%, P=0.003) and beta-blocker therapy (73% vs. 57.6%, P=0.042) and had a markedly reduced functional capacity (6MWD 221±100m vs. 265±105m, P=0.001). At multivariate Cox proportional hazards regression analysis, independent predictors of survival at follow-up were lower comorbidity rate, a better-preserved renal function, lower use of diuretics, and a higher 6MWD at discharge (Harrell's C = 0.707). CONCLUSIONS: Patients attending residential CR after TAVR are very old with significant comorbidity. The overall 3-year mortality rate after CR discharge is high. Our findings suggest the need for individually tailored follow-up care in patients discharged from CR after TAVR to address their residual exercise capacity, comorbidities, and renal function impairment.

Positive affect as a predictor of non-pharmacological adherence in older Chronic Heart Failure (CHF) patients undergoing cardiac rehabilitation.

In Chronic Heart Failure (CHF) patients, psychological and cognitive variables and their association with treatment adherence have been extensively reported in the literature, but few are the investigations in older people. The present study aimed to evaluate the psychological, cognitive, and adherence to treatment profile of older (>65 years) CHF patients, the interrelation between these variables, and identify possible independent predictors of self-reported treatment adherence. CHF inpatients undergoing cardiac rehabilitation were assessed for: anxiety, depression, cognitive impairment, positive and negative affect, and self-reported adherence (adherence antecedents, pharmacological adherence, and non-pharmacological adherence). 100 CHF inpatients (mean age: 74.9 ± 7.1 years) were recruited. 16% of patients showed anxiety and 24.5% depressive symptoms; 4% presented cognitive decline. Cognitive functioning negatively correlated to depression, anxiety, and negative affect (p < 0.01). The adherence antecedents (disease acceptance, adaptation, knowledge, and socio-familiar support) negatively correlated to anxiety (p < 0.05), depression (p < 0.001), and negative affect (p < 0.05), while they positively correlated to positive affect (p < 0.01). Pharmacological adherence negatively correlated to anxiety and negative affect (p < 0.05). Conversely, non-pharmacological adherence and positive affect positively correlated (p < 0.05). Furthermore, depression and anxiety negatively predicted adherence antecedents (ß = -0.162, p = 0.037) and pharmacological adherence (ß = -0.171, p = 0.036), respectively. Finally, positive affect was found as an independent predictor of non-pharmacological adherence (ß = 0.133, p = 0.004). In cardiac rehabilitation, a specific psychological assessment focused on anxiety, depression, and affect can provide useful information to manage CHF older patients' care related to treatment adherence. In particular, positive affect should be targeted in future interventions to foster patients' non-pharmacological adherence.

The Clinical Frailty Scale (CFS) employment in the frailty assessment of patients suffering from Non-Communicable Diseases (NCDs): A systematic review.

Background: The Clinical Frailty Scale (CFS) is a well-established tool that has been widely employed to assess patients' frailty status and to predict clinical outcomes in the acute phase of a disease, but more information is needed to define the implications that this tool have when dealing with Non-Communicable Diseases (NCDs). Methods: An electronic literature search was performed on PubMed, Scopus, EMBASE, Web of Science, and EBSCO databases to identify studies employing the CFS to assess frailty in patients with NCDs. Findings: After database searching, article suitability evaluation, and studies' quality assessment, 43 studies were included in the systematic review. Researches were conducted mostly in Japan (37.5%), and half of the studies were focused on cardiovascular diseases (46.42%), followed by cancer (25.00%), and diabetes (10.71%). Simplicity (39.29%), efficacy (37.5%), and rapidity (16.07%) were the CFS characteristics mostly appreciated by the authors of the studies. The CFS-related results indicated that its scores were associated with patients' clinical outcomes (33.92%), with the presence of the disease (12.5%) and, with clinical decision making (10.71%). Furthermore, CFS resulted as a predictor of life expectancy in 23 studies (41.07%), clinical outcomes in 12 studies (21.43%), and hospital admissions/readmissions in 6 studies (10.71%). Discussion: CFS was found to be a well-established and useful tool to assess frailty in NCDs, too. It resulted to be related to the most important disease-related clinical characteristics and, thus, it should be always considered as an important step in the multidisciplinary evaluation of frail and chronic patients. Systematic review registration: https://www.crd.york.ac.uk/PROSPERO/display_record.asp? PROSPERO 2021, ID: CRD42021224214.

Cognitive impairment, frailty and rehabilitation outcome in older cardiorespiratory patients. DEC_FRAinRIAB: Study protocol.

BACKGROUND: Chronic heart failure (CHF) and chronic obstructive pulmonary disease (COPD) are two clinical conditions often associated with functional worsening, cognitive dysfunctions, treatment non-adherence, psychological distress and poor quality of life (QoL). In addition, since patients suffering from these conditions are often older adults, the presence of frailty syndrome could worsen the clinical situation. METHODS AND DESIGN: This study protocol of a prospective multi-center clinical trial, will be conducted at two hospitals of the Istituti Clinici Scientifici Maugeri IRCCS group, from July 2020 until December 2022. CHF and COPD older patients (age ≥65) will undergo a multidisciplinary assessment at admission, discharge and at 6 months follow-up, from an inpatient rehabilitation program: disease-related clinical characteristics, functional variables, cognitive screening, treatment adherence, anxiety, depression, QoL and frailty. The estimated sample size will consist of 300 patients. DISCUSSION: The expected results are related to the possibility of an improvement in the areas of intervention after the rehabilitative program and the maintenance of these improvements over time. The assessment of clinical and functional status, cognitive impairment, treatment adherence, psychosocial characteristics, and frailty could provide more specific and useful information about the main features to be considered in the evaluation and treatment of older patients suffering from CHF and COPD undergoing a rehabilitative pathway. TRIAL REGISTRATION: The study has been registered on January 28, 2022 with the ClinicalTrials.gov NCT05230927 registration number (clinicaltrials.gov/ct2/show/NCT05230927).

A Blood Bank Standardized Production of Human Platelet Lysate for Mesenchymal Stromal Cell Expansion: Proteomic Characterization and Biological Effects.

Human platelet lysate (hPL) is considered a valid substitute to fetal bovine serum (FBS) in the expansion of mesenchymal stromal cells (MSC), and it is commonly produced starting from intermediate side products of whole blood donations. Through freeze-thaw cycles, hPL is highly enriched in chemokines, growth factors, and adhesion and immunologic molecules. Cell therapy protocols, using hPL instead of FBS for the expansion of cells, are approved by regulatory authorities without concerns, and its administration in patients is considered safe. However, published data are fairly difficult to compare, since the production of hPL is highly variable. This study proposes to optimize and standardize the hPL productive process by using instruments, technologies, and quality/safety standards required for blood bank activities and products. The quality and improved selection of the starting material (i.e., the whole blood), together with the improvement of the production process, guarantee a product characterized by higher content and quality of growth factors as well as a reduction in batch-to-batch variability. By increasing the number of freeze/thaw cycles from one (hPL1c) to four (hPL4c), we obtained a favorable effect on the release of growth factors from platelet α granules. Those changes have directly translated into biological effects leading to a decreasing doubling time (DT) of MSC expansion at 7 days (49.41 ± 2.62 vs. 40.61 ± 1.11 h, p < 0.001). Furthermore, mass spectrometry (MS)-based evaluation has shown that the proliferative effects of hPL4c are also combined with a lower batch-to-batch variability (10-15 vs. 21-31%) at the proteomic level. In conclusion, we have considered lot-to-lot hPL variability, and by the strict application of blood bank standards, we have obtained a standardized, reproducible, safe, cheap, and ready-to-use product.

Delphi consensus recommendations on how to provide cardiovascular rehabilitation in the COVID-19 era.

This Delphi consensus by 28 experts from the European Association of Preventive Cardiology (EAPC) provides initial recommendations on how cardiovascular rehabilitation (CR) facilities should modulate their activities in view of the ongoing coronavirus disease 2019 (COVID-19) pandemic. A total number of 150 statements were selected and graded by Likert scale [from -5 (strongly disagree) to +5 (strongly agree)], starting from six open-ended questions on (i) referral criteria, (ii) optimal timing and setting, (iii) core components, (iv) structure-based metrics, (v) process-based metrics, and (vi) quality indicators. Consensus was reached on 58 (39%) statements, 48 'for' and 10 'against' respectively, mainly in the field of referral, core components, and structure of CR activities, in a comprehensive way suitable for managing cardiac COVID-19 patients. Panelists oriented consensus towards maintaining usual activities on traditional patient groups referred to CR, without significant downgrading of intervention in case of COVID-19 as a comorbidity. Moreover, it has been suggested to consider COVID-19 patients as a referral group to CR per se when the viral disease is complicated by acute cardiovascular (CV) events; in these patients, the potential development of COVID-related CV sequelae, as well as of pulmonary arterial hypertension, needs to be focused. This framework might be used to orient organization and operational of CR programmes during the COVID-19 crisis.

Psychomotor speed as a predictor of functional status in older chronic heart failure (CHF) patients attending cardiac rehabilitation.

BACKGROUND: The association among psychological, neuropsychological dysfunctions and functional/clinical variables in Chronic Heart Failure (CHF) has been extensively addressed in literature. However, only a few studies investigated those associations in the older population. PURPOSE: To evaluate the psychological/neuropsychological profile of older CHF patients, to explore the interrelation with clinical/functional variables and to identify potential independent predictors of patients' functional status. METHODS: This study was conducted with a multi-center observational design. The following assessments were performed: anxiety (Hospital Anxiety and Depression Scale, HADS), depression (Geriatric Depression Scale, GDS), cognitive impairment (Addenbrooke's Cognitive Examination Revised, ACE-R), executive functions (Frontal Assessment Battery, FAB), constructive abilities (Clock Drawing Test, CDT), psychomotor speed and alternated attention (Trail Making Test, TMT-A/B), functional status (6-minute walking test, 6MWT) and clinical variables (New York Heart Association, NYHA; Brain Natriuretic Peptide, BNP; left ventricular ejection fraction, LVEF; left ventricular end diastolic diameter, LVEDD; left ventricular end diastolic volume, LVEDV; tricuspid annular plane systolic excursion, TAPSE). RESULTS: 100 CHF patients (mean age: 74.9±7.1 years; mean LVEF: 36.1±13.4) were included in the study. Anxious and depressive symptoms were observed in 16% and 24,5% of patients, respectively. Age was related to TMT-A and CDT (r = 0.49, p<0.001 and r = -0.32, p = 0.001, respectively), Log-BNP was related to ACE-R-Fluency subtest, (r = -0.22, p = 0.034), and 6MWT was related to ACE-R-Memory subtest and TMT-A (r = 0.24, p = 0.031 and r = -0.32, p = 0.005, respectively). Both anxiety and depression symptoms were related to ACE-R-Total score (r = -0.25, p = 0.013 and r = -0.32, p = 0.002, respectively) and depressive symptoms were related to CDT (r = -0.23, p = 0.024). At multiple regression analysis, Log-BNP and TMT-A were significant and independent predictors of functional status: worse findings on Log-BNP and TMT-A were associated with shorter distance walked at the 6MWT. CONCLUSIONS: Psychological and neuropsychological screening, along with the assessment of psychomotor speed (TMT-A), may provide useful information for older CHF patients undergoing cardiac rehabilitation.

Impedance-Based Monitoring of Mesenchymal Stromal Cell Three-Dimensional Proliferation Using Aerosol Jet Printed Sensors: A Tissue Engineering Application.

One of the main hurdles to improving scaffolds for regenerative medicine is the development of non-invasive methods to monitor cell proliferation within three-dimensional environments. Recently, an electrical impedance-based approach has been identified as promising for three-dimensional proliferation assays. A low-cost impedance-based solution, easily integrable with multi-well plates, is here presented. Sensors were developed using biocompatible carbon-based ink on foldable polyimide substrates by means of a novel aerosol jet printing technique. The setup was tested to monitor the proliferation of human mesenchymal stromal cells into previously validated gelatin-chitosan hybrid hydrogel scaffolds. Reliability of the methodology was assessed comparing variations of the electrical impedance parameters with the outcomes of enzymatic proliferation assay. Results obtained showed a magnitude increase and a phase angle decrease at 4 kHz (maximum of 2.5 kΩ and -9 degrees) and an exponential increase of the modeled resistance and capacitance components due to the cell proliferation (maximum of 1.5 kΩ and 200 nF). A statistically significant relationship with enzymatic assay outcomes could be detected for both phase angle and electric model parameters. Overall, these findings support the potentiality of this non-invasive approach for continuous monitoring of scaffold-based cultures, being also promising in the perspective of optimizing the scaffold-culture system.

[Implementation of the ICD-ICF model in rehabilitation medicine: report of a clinical case in rehabilitative cardiology]. / Implementazione del modello ICD-ICF in medicina riabilitativa: presentazione di un caso clinico in cardiologia riabilitativa.

SUMMARY: This patient entered a Cardiac Rehabilitation Program after coronary artery bypass graft. Concomitant diseases and the degree of disability have been coded according to International Classification of Functioning (ICF). Rehabilitation multidisciplinary program has been started (physician, nurses, physiotherapist and nutritionist); atrial fibrillation, anaemia, pleural effusion, surgical wounds inflammation were treated. Educational program allowed a better knowledge of the diseases the patient is bearing; low functional capability diagnosed at admittance improved thanks to the coordinated intervention of professionals involved. Coding diseases and disabilities at admission ensured a detailed identification of patient's issues and allowed the identification and the proposal for a targeted rehabilitation program. The improvement of medical ICF codes b280, b810 and b820, of physiotherapeutic codes b235, d450, d4551 and d455 and of nursing codes b280, b810 and b820 depends on the marked reduction of disability level.

Counting circulating endothelial cells in allo-HSCT: an ad hoc designed polychromatic flowcytometry-based panel versus the CellSearch System.

Physio-pathologic interrelationships between endothelial layer and graft-versus-host disease (GVHD) have been described leading to assess the entity "endothelial GVHD" as the early step for clinical manifestations of acute GVHD. The availability of the CellSearch system has allowed us to monitor Circulating Endothelial Cells (CEC) changes in allogeneic hematopoietic stem cell transplantation (allo-HSCT) as useful tool to help clinicians in GVHD diagnostic definition. We have compared CEC counts generated by an ad hoc designed polychromatic-flowcytometry (PFC) Lyotube with those of the CellSearch system. CEC were counted in parallel at 5 timepoints in 50 patients with malignant hematologic disorders undergoing allo-HSCT (ClinicalTrials.gov, NCT02064972). Spearman rank correlation showed significant association between CEC values at all time points (p = 0.0001). The limits of agreement was demonstrated by Bland Altman plot analysis, showing bias not significant at T1, T3, T4, while at T2 and T5 resulted not estimable. Moreover, Passing Bablok regression analysis showed not significant differences between BD Lyotube and CellSearch system. We show that CEC counts, generated with either the CellSearch system or the PFC-based panel, have a superimposable kinetic in allo-HSCT patients and that both counting procedures hold the potential to enter clinical routine as a suitable tool to assist clinicians in GVHD diagnosis.

Exercise Prescription in Patients with Different Combinations of Cardiovascular Disease Risk Factors: A Consensus Statement from the EXPERT Working Group.

Whereas exercise training is key in the management of patients with cardiovascular disease (CVD) risk (obesity, diabetes, dyslipidaemia, hypertension), clinicians experience difficulties in how to optimally prescribe exercise in patients with different CVD risk factors. Therefore, a consensus statement for state-of-the-art exercise prescription in patients with combinations of CVD risk factors as integrated into a digital training and decision support system (the EXercise Prescription in Everyday practice & Rehabilitative Training (EXPERT) tool) needed to be established. EXPERT working group members systematically reviewed the literature for meta-analyses, systematic reviews and/or clinical studies addressing exercise prescriptions in specific CVD risk factors and formulated exercise recommendations (exercise training intensity, frequency, volume and type, session and programme duration) and exercise safety precautions, for obesity, arterial hypertension, type 1 and 2 diabetes, and dyslipidaemia. The impact of physical fitness, CVD risk altering medications and adverse events during exercise testing was further taken into account to fine-tune this exercise prescription. An algorithm, supported by the interactive EXPERT tool, was developed by Hasselt University based on these data. Specific exercise recommendations were formulated with the aim to decrease adipose tissue mass, improve glycaemic control and blood lipid profile, and lower blood pressure. The impact of medications to improve CVD risk, adverse events during exercise testing and physical fitness was also taken into account. Simulations were made of how the EXPERT tool provides exercise prescriptions according to the variables provided. In this paper, state-of-the-art exercise prescription to patients with combinations of CVD risk factors is formulated, and it is shown how the EXPERT tool may assist clinicians. This contributes to an appropriately tailored exercise regimen for every CVD risk patient.

The European Association of Preventive Cardiology Exercise Prescription in Everyday Practice and Rehabilitative Training (EXPERT) tool: A digital training and decision support system for optimized exercise prescription in cardiovascular disease. Concept, definitions and construction methodology.

Background Exercise rehabilitation is highly recommended by current guidelines on prevention of cardiovascular disease, but its implementation is still poor. Many clinicians experience difficulties in prescribing exercise in the presence of different concomitant cardiovascular diseases and risk factors within the same patient. It was aimed to develop a digital training and decision support system for exercise prescription in cardiovascular disease patients in clinical practice: the European Association of Preventive Cardiology Exercise Prescription in Everyday Practice and Rehabilitative Training (EXPERT) tool. Methods EXPERT working group members were requested to define (a) diagnostic criteria for specific cardiovascular diseases, cardiovascular disease risk factors, and other chronic non-cardiovascular conditions, (b) primary goals of exercise intervention, (c) disease-specific prescription of exercise training (intensity, frequency, volume, type, session and programme duration), and (d) exercise training safety advices. The impact of exercise tolerance, common cardiovascular medications and adverse events during exercise testing were further taken into account for optimized exercise prescription. Results Exercise training recommendations and safety advices were formulated for 10 cardiovascular diseases, five cardiovascular disease risk factors (type 1 and 2 diabetes, obesity, hypertension, hypercholesterolaemia), and three common chronic non-cardiovascular conditions (lung and renal failure and sarcopaenia), but also accounted for baseline exercise tolerance, common cardiovascular medications and occurrence of adverse events during exercise testing. An algorithm, supported by an interactive tool, was constructed based on these data. This training and decision support system automatically provides an exercise prescription according to the variables provided. Conclusion This digital training and decision support system may contribute in overcoming barriers in exercise implementation in common cardiovascular diseases.

Relationship among body mass index, NT-proBNP, and mortality in decompensated chronic heart failure.

BACKGROUND: Obesity has been suggested to confer a survival benefit in acute heart failure. The concentrations of NT-proBNP may be reduced in patients with high body mass index (BMI). OBJECTIVES: To investigate the relationship among BMI, NT-proBNP, and mortality risk in decompensated chronic heart failure (DCHF). METHODS: This was a retrospective study. We studied 1001 patients with DCHF. Hazard ratios (HR) were calculated with Cox regression analysis. RESULTS: During the 1-year follow-up, 295 patients died. Compared with normal-weight patients, the unadjusted HR for death were 1.02 (95% CIs 0.79-1.33; p = 0.862) for patients with a BMI of 25.0-29.9 kg/m2 and 0.83 (95% CIs 0.61-1.12; p = 0.213) for patients with a BMI ≥ 30 kg/m2. NT-proBNP remained independently associated with mortality across the BMI categories. There was no statistically significant interaction between BMI and NT-proBNP levels for risk prediction. CONCLUSIONS: Obesity was not associated with mortality risk. NT-proBNP remained an independent prognostic factor across the BMI categories.

Exercise-based cardiac rehabilitation in cardiac resynchronization therapy recipients: A primer for practicing clinicians.

Cardiac resynchronization therapy (CRT) is a therapeutic option of increasing importance for chronic heart failure (CHF) and criteria for implantation now concern a large amount of patient populations. As a consequence, subjects with ongoing CRT (or immediately after CRT implantation) are more often referred to Cardiac Rehabilitation (CR) programmes, and it has been recently estimated that about one third of CHF patients attending CR in Italy currently have this kind of device. The presence of CRT represents a modulating factor for exercise prescription and monitoring, since CRT patients may be considered per se as a target group for CR. Exercise therapy (ET) increases benefits from CRT on functional capacity, and recent evidence suggests an adjuvant role of ET in improving cardiovascular prognosis also. Both aerobic endurance and resistance training activities may involve CHF patients with CRT, while the potential role of aerobic interval training needs more studies and evidence. Prescription of an ET program should be associated with information regarding device programming and possible limiting factors associated with pacing therapy, tailoring of the basic principles of ET (in terms of type of exercise, intensity and program duration) in this patient group is mandatory.

Altered fasting glycemia in cardiac patients during in-hospital rehabilitation: impact on short and long-term follow-up.

BACKGROUND AND AIMS: Hospitalized patients after acute cardiovascular events have poorer prognosis if glucose regulation is diagnosed as abnormal. We compared the short and long-term outcome of patients with newly diagnosed altered fasting glycemia (AFG) to that of known diabetic patients and patients with normal glucose regulation (NGR) after admission to cardiac rehabilitation. METHODS: We retrospectively analyzed 2490 consecutive patients. Three groups were identified: known diabetes mellitus (n = 540, 22%), fasting glycemia above 110 mg/dl (AFG, n = 269, 11%), and fasting glycemia 110 mg/dl or less (NGR, n = 1681, 67%). Clinical variables, complications, and all-cause mortality were evaluated. RESULTS: At follow-up (median 3.1 ±â€Š2.4 years), after adjustment for age, sex, BMI, left ventricular ejection fraction, history of coronary artery disease, AFG had a significantly longer hospital stay versus NGR (21 ±â€Š8 versus 20 ±â€Š8 days; P = 0.019) and higher risk of paroxysmal atrial fibrillation (P = 0.041), pleural/pericardial effusions (P < 0.001), skin complications (P = 0.033), other events (P = 0.001), and blood tests (urea: P = 0.007; white blood cells: P = 0.002; neutrophils: P < 0.001; creatinine: P = 0.022). All-cause mortality was significantly higher in diabetes mellitus versus NGR (odds ratio 1.61, 95% confidence interval 1.17-2.21); a nonsignificant trend was observed in AFG versus NGR (odds ratio 1.23, 95% confidence interval 0.77-1.98). CONCLUSIONS: A high AFG prevalence in cardiac patients admitted to rehabilitation was observed. AFG patients were more vulnerable than NGR patients, had higher complication rates independently of covariates, and required longer hospital stay. AFG was not a significant predictor of all-cause mortality at 3 years, whereas DM was.

Prognostic impact of comorbidities in hospitalized patients with acute exacerbation of chronic heart failure.

BACKGROUND: To assess the impact of comorbidities on long-term all-cause mortality in patients hospitalized with exacerbated signs/symptoms of previously chronic stable HF (AE-CHF). METHODS: 1119 patients admitted for AE-CHF and with NT-proBNP levels >900pg/mL were enrolled. Univariable and multivariable Cox analyses were performed to assess the association of age, gender, hypertension, diabetes, obesity, atrial fibrillation, coronary heart disease (CHD), chronic obstructive pulmonary disease, previous cerebrovascular accidents, chronic liver disease (CLD), thyroid disease, renal impairment (RI), and anemia with 3-year all-cause mortality. RESULTS: During the follow-up, 441 patients died and 126 underwent heart transplantation (HT) or ventricular assist device (VAD) implantation. 45.8% of the fatal events and 52.4% of HT/VAD implantations occurred within 180days after admission. Increasing age (p=.012), obesity (p=.037), atrial fibrillation (p=.030), CHD (p=.015), CLD (p=.001), RI (p<.001), and anemia (p<.001) were independently associated with 3-year all-cause mortality. Most of the prognostic impact of CHD, took place within the first 180days after admission. Male gender was associated with mortality beyond 180days. Compared with normal weight, obesity was associated with better overall survival. Obese patients, however, had significantly lower NT-proBNP concentrations and less frequently presented with hypotension, hyponatremia, and severe left ventricular systolic dysfunction, despite a similar prevalence of severe dyspnea at admission. CONCLUSIONS: Several comorbidities are associated with long-term risk of death in hospitalized patients with worsening HF, although the nature of this association does appear to be complex. Our data may help to raise awareness about the clinical relevance of comorbid conditions.

Incremental utility of prognostic variables at discharge for risk prediction in hospitalized patients with acutely decompensated chronic heart failure.

OBJECTIVES: To assess the incremental prognostic utility of discharge serum creatinine (SCr), systolic blood pressure (SBP), and NT-proBNP and sodium concentrations in hospitalized patients with acutely decompensated chronic heart failure. BACKGROUND: Whether key prognostic variables at discharge provide incremental prognostic information beyond that provided by a model based on admission variables (referent) remains incompletely defined. METHODS: The primary outcome was a composite of death, urgent heart transplantation, or ventricular assist device implantation at 1 year. The gain in predictive performance was assessed using C index, Bayesian Information Criterion, and Net Reclassification Improvement. RESULTS: The best fit was obtained when discharge NT-proBNP was added to the referent model. No interaction between admission and discharge NT-proBNP was found. Discharge SCr, SBP, and sodium did not improve goodness-of-fit. CONCLUSIONS: Admission and discharge NT-proBNP provide complementary and independent prognostic information; as such, they should be taken into account concurrently.

Prospective Use of Microvolt T-Wave Alternans Testing to Guide Primary Prevention Implantable Cardioverter Defibrillator Therapy.

BACKGROUND: We hypothesized that a negative microvolt T-wave alternans (MTWA) test would identify patients unlikely to benefit from primary prevention implantable cardioverter defibrillator (ICD) therapy in a prospective cohort. METHODS AND RESULTS: Data were pooled from 8 centers where MTWA testing was performed specifically for the purpose of guiding primary prevention ICD implantation. Cohorts were included if the ratio of ICDs implanted in patients who were MTWA "non-negative" to patients who were MTWA negative was >2:1, indicating that MTWA testing had a significant impact on the decision to implant an ICD. The pooled cohort included 651 patients: 371 MTWA non-negative and 280 MTWA negative. Among non-negative patients, 62% underwent ICD implantation whereas only 13% of MTWA-negative patients received an ICD (P<0.01). Despite a substantially lower prevalence of ICDs, long-term survival (6.9 years) was significantly better among MTWA-negative patients (68.2% non-negative vs. 87.1% negative, P=0.026). CONCLUSIONS: MTWA-negative patients had significantly better survival than MTWA non-negative patients, the majority of whom had ICDs. Despite a very low prevalence of ICDs, long-term survival among patients with left ventricular ejection fraction ≤40% and a negative MTWA test was better than in the ICD arm of any study to date that has demonstrated a benefit of ICDs. This provides further evidence that MTWA-negative patients are unlikely to benefit from primary prevention ICD therapy.