Diabetes and SGLT2-iss inhibitors in patients with heart failure with preserved or mid-range left ventricular ejection fractions.

Diabetic patients frequently develop heart failure with preserved (HFpEF) or mid-range (HFmEF) cardiac ejection fractions. This condition may be secondary to diabetic cardiomyopathy or one of several relevant comorbidities, mainly hypertension. Several mechanisms link diabetes to HFpEF or HFmEF. Among these, non-enzymatic glycation of interstitial proteins, lipotoxicity, and endothelial dysfunction may promote structural damage and ultimate lead to heart failure. Findings from several large-scale trials indicated that treatment with sodium/glucose cotransporter 2 inhibitors (SGLT2-iss) resulted in significant improvements in cardiovascular outcomes in diabetic patients with high cardiovascular risk. However, there is currently some evidence that suggests a clinical advantage of using SGLT2-iss specifically in cases of HFpEF or HFmEF. Preclinical and clinical studies revealed that SGLT2-iss treatment results in a reduction in left ventricular mass and improved diastolic function. While some of the beneficial effects of SGLT2-iss have already been characterized (e.g., increased natriuresis and diuresis as well as reduced blood pressure, plasma volume, and arterial stiffness, and nephron-protective activities), there is increasing evidence suggesting that SGLT2-iss may have direct actions on the heart. These findings include SGLT2-iss-mediated reductions in the expression of hypertrophic foetal genes and diastolic myofilaments stiffness, increases in global phosphorylation of myofilament regulatory proteins (in HFpEF), inhibition of cardiac late sodium channel current and Na+/H+ exchanger activity, metabolic shifts, and effects on calcium cycling. Preliminary data from previously published studies suggest that SGLT2-iss could be useful for the treatment of HFpEF and HFmEF. Several large ongoing trials, including DELIVER AND EMPEROR -preserved have been designed to evalute the efficacy of SGLT2-iss in improving clinical outcomes in patients diagnosed with HFpEF. The goal of this manuscript is to review the use of SGLT2-iss inhibitors for HFpEF or HFmEF associated with diabetes.

Characteristics, Outcomes, and Long-Term Survival of Patients With Heart Failure Undergoing Inpatient Cardiac Rehabilitation.

OBJECTIVE: To investigate the association of cardiac rehabilitation (CR) participation with all-cause mortality after a hospitalization for heart failure (HF) and to describe the characteristics and functional and clinical outcomes of HF patients undergoing inpatient CR. DESIGN: Multicenter cohort study. The association between CR participation and all-cause mortality from discharge from the acute care setting was assessed using Cox regression analysis adjusting for established prognostic factors. SETTING: Six inpatient rehabilitation facilities. PARTICIPANTS: A total of 3219 patients with HF admitted to inpatient CR between January 2013 and December 2016. Of these patients, 1455 had been transferred directly from acute care hospitals after a hospitalization for HF (CR-group 1) and 1764 had been admitted from the community due to worsening functional disability or worsening clinical conditions (CR-group 2). Serving as a control group were 633 patients not referred to CR after a hospitalization for HF served as control group (non-CR group). INTERVENTIONS: Cardiac rehabilitation. MAIN OUTCOME MEASURES: Long-term mortality. Secondary outcomes were: (1) change in functional capacity, as assessed by change in 6-minute walking distance from admission to discharge; (2) clinical outcomes of the index inpatient rehabilitation admission, including in-hospital mortality and unplanned readmission to the acute care. RESULTS: Compared with the non-CR group, the adjusted hazard ratios of mortality at 1, 3, and 5 years for CR-group 1 patients were 0.82 (range, 0.68-0.97), 0.81 (range, 0.71-0.93), and 0.80 (range, 0.70-0.91). The 6-minute walking distance increased from 230-292 meters (P<.001), and 43.4% of the patients gained >50 m improvement. Overall, 2.5% of the patients died in hospital and 4.7% of the patients experienced unplanned readmissions to acute care, with significant differences between group 1 and group 2. CONCLUSIONS: Our data show that inpatient CR is effective in improving functional capacity and suggest that inpatient CR provided in the earliest period after a hospitalization for HF is associated with long-term improved survival.

Malnutrition in patients admitted to in-hospital cardiac rehabilitation: Clinical correlates and association with mortality.

Malnutrition is highly prevalent among hospitalized patients; thus, an accurate identification of malnutrition could improve the outcome of these patients. The aim of the present paper was to apply multiple methods to evaluate the prevalence of malnutrition and clinical correlates in patients admitted to in-hospital cardiac rehabilitation.  We performed a prospective study of 426 patients admitted to in-hospital cardiac rehabilitation: 282 (66.2%) had undergone a major cardiac surgery and 144 (34.8%) had experienced heart failure. The albumin level and Mini Nutritional Assessment (MNA) scores were applied to evaluate the nutritional status of these patients. Serum albumin levels were < 3.5 g/dl in 147 (34.5%) patients, and MNA scores were < 24 in 179 (42.0%) patients. Patients with malnutrition or a risk of malnutrition had lower haemoglobin values, lower EuroQol scores and poorer functional status. Female gender, age, functional status and Cumulative Illness Rating Scale severity were predictors of malnutrition. Over a median follow-up of 47 months, MNA scores <24 were associated with higher mortality, even after correction for confounding variables. In conclusion, in patients admitted to in-hospital cardiac rehabilitation, malnutrition and risk of malnutrition frequently occur and are associated with poor functional status, higher clinical complication rates and long-term mortality.

Cardiovascular Death Risk in Recovered Mid-Range Ejection Fraction Heart Failure: Insights From Cardiopulmonary Exercise Test.

BACKGROUND: Heart failure with midrange ejection fraction (HFmrEF) represents a heterogeneous category where phenotype, as well as prognostic assessment, remains debated. The present study explores a specific HFmrEF subset, namely those who recovered from a reduced EF (rec-HFmrEF) and, particularly, it focuses on the possible additive prognostic role of cardiopulmonary exercise testing. METHODS AND RESULTS: We analyzed data from 4535 patients with HFrEF and 1176 patients with rec-HFmrEF from the Metabolic Exercise combined with Cardiac and Kidney Indexes database. The end point was cardiovascular death at 5 years. The median follow-up was 1343 days (25th-75th range 627-2403 days). Cardiovascular death occurred in 552 HFrEF and 61 rec-HFmrEF patients. The multivariate analysis confirmed an independent role of the MECKI score's variables in HFrEF (C-index = 0.744) whereas, in the rec-HFmrEF group, only age and peak oxygen uptake (pVO2) remained associated to the end point (C-index = 0.745). A peak oxygen uptake of ≤55% of predicted and a ventilatory efficiency of ≥31 resulted as the most accurate cut-off values in the outcome prediction. CONCLUSIONS: Present data support the cardiopulmonary exercise test and, particularly, the peak oxygen uptake, as a useful tool in the rec-HFmrEF prognostic assessment. A peak VO2 of ≤55% predicted and ventilatory efficiency of ≥31 might help to identify a high-risk rec-HFmrEF subgroup.

Association Between Malnutrition and Outcomes in Patients With Severe Ischemic Stroke Undergoing Rehabilitation.

OBJECTIVE: To investigate the incremental prognostic significance of malnutrition in patients with severe poststroke disability. DESIGN: Retrospective cohort study. The patients were recruited from 3 specialized inpatient rehabilitation facilities. Nutritional status was assessed using the Prognostic Nutritional Index (PNI), which is calculated from serum albumin and total lymphocyte count. Scores >38 points reflect normal nutrition status, scores of 35-38 indicate moderate malnutrition, and scores <35 indicate severe malnutrition. The association of PNI categories with outcomes was assessed using multivariable regression analyses. SETTING: Inpatient rehabilitation facility. PARTICIPANTS: Patients (N=668) with ischemic stroke admitted to inpatient rehabilitation within 90 days from stroke occurrence and classified as Case-Mix Groups 0108, 0109, and 0110 of the current Medicare case-mix classification system. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Three outcomes were examined: (1) the combined outcome of transfer to acute care and death within 90 days from admission to rehabilitation; (2) 2-year mortality; and (3) FIM motor effectiveness, calculated as (FIM motor change/maximum FIM motor-admission FIM motor score)×100. RESULTS: Overall, the median time to rehabilitation admission was 18 days (range, 12-26 days). The prevalence of moderate and severe malnutrition was 12.7% and 11.5%, respectively. Ninety-one patients (13.6%) experienced the combined outcome. After adjusting for independent predictors including sex, atrial fibrillation, dysphagia, FIM cognitive score, and hemoglobin levels, neither moderate (P=.280) nor severe malnutrition (P=.482) were associated with the combined outcome. Similar results were observed when looking at 2-year mortality. Overall, FIM motor effectiveness was 30%±24%. After adjusting for independent predictors, severe malnutrition (ß coefficient -0.458±0.216; P=.034) was associated with FIM motor effectiveness. CONCLUSIONS: Approximately 1 in every 9 patients presented severe malnutrition. On top of the independent predictors, severe malnutrition did not provide additional prognostic information concerning risk of the combined outcome or 2-year mortality. Conversely, severe malnutrition was associated with poorer functional outcome as expressed by FIM motor effectiveness.

Rehabilitation Outcomes of Patients With Severe Disability Poststroke.

OBJECTIVE: To characterize rehabilitation outcomes of patients with severe poststroke motor impairment (MI) and develop a predictive model for treatment failure. DESIGN: Retrospective cohort study. Correlates of treatment failure, defined as the persistence of severe MI after rehabilitation, were identified using logistic regression analysis. Then, an integer-based scoring rule was developed from the logistic model. SETTING: Three specialized inpatient rehabilitation facilities. PARTICIPANTS: Patients (N=1265) classified as case-mix groups (CMGs) 0108, 0109, and 0110 of the Medicare classification system. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURE: Change in the severity of MI, as assessed by the FIM, from admission to discharge. RESULTS: Median FIM-motor (FIM-M) score increased from 17 (interquartile range [IQR] 14-23) to 38 (IQR, 25-55) points. Median proportional recovery, as expressed by FIM-M effectiveness, was 26% (IQR, 12-47). Median FIM-M change was 18 (IQR, 9-34) points. About 38.5% patients achieved the minimal clinically important difference. Eighteen point six percent and 32.0% of the patients recovered to a stage of either mild (FIM-M ≥62) or moderate (FIM-M 38-61) MI, respectively. All between-CMG differences were statistically significant. Outcomes have also been analyzed according to classification systems used in Australia and Canada. The scoring rule had an area under the curve of 0.833 (95% confidence interval, 0.808-0.858). Decision curve analysis displayed large net benefit of using the risk score compared with the treat all strategy. CONCLUSIONS: This study provides a snapshot of rehabilitation outcomes in a large cohort of patients with severe poststroke MI, thus filling a gap in knowledge. The scoring rule accurately identified the patients at risk for treatment failure.

Measures of hospital competition and their impact on early mortality for congestive heart failure, acute myocardial infarction and cardiac surgery.

OBJECTIVE: To measure competition amongst providers and to examine whether a correlation exists with hospitals mortality for congestive heart failure (CHF), acute myocardial infarction (AMI), isolated-coronary artery bypass graft (CABG) or valve surgery. DESIGN: Cross-sectional study based on publically available data from the National Outcome Evaluation Program (Edition 2016) of the Italian Agency for Regional Health Services. SETTING AND PARTICIPANTS: Patients discharged during 2015 for CHF or AMI, and between 2014 and 2015 for cardiac surgery (respectively, from 662, 395 and 91 hospitals). MAIN OUTCOME MEASURES: Risk-adjusted mortality rates at 30 days and measures of hospital competition for areas centred on hospital' location (fixed-radius 50-150 km, variable-radius to capture 10-30 hospitals and 6-10% of national volume). Competition was estimated as number of providers and Herfindahl-Hirschman Index (HHI). RESULTS: Indicators of competitions varied by condition and were sensitive to method used for the area definition. Hospital mortality after AMI and valve surgery increased with competition in areas identified by the variable-radius method (higher rates for a greater number of hospitals or lower HHIs). In area with fixed radius of 100-150 km, competition reduced mortality after CABG procedures (lower rates for a greater number of hospitals or smaller HHIs). Neither the number of hospitals nor HHI correlated with outcomes in CHF. CONCLUSIONS: The measures of hospital competition changed according to definition of local market and results in mortality correlations varied among conditions. Understanding the relationship between hospital competition and outcomes is important to identify strategies to improve quality of care.

[Rehabilitation medicine and appropriateness criteria: between chronicity, multi-morbidity and complexity]. / La medicina riabilitativa e i criteri di appropriatezza: tra cronicità, multimorbilità e complessità.

SUMMARY: In the last two decades, population aging has led to a substantial increase in the number of people living with moderate-to-severe disability and, consequently, an increased demand for rehabilitation care. It is estimated that, currently, 2.8 million people live with severe disability in Italy. Although greater access to rehabilitation care is required to meet the needs of disabled patients, the capacity to provide rehabilitation has not changed over the last years and fails to meet current rehabilitation needs. Efforts should be devoted for aligning the capacity to provide rehabilitation care to the increased demand for rehabilitation care.

Critical Appraisal of Multivariable Prognostic Scores in Heart Failure: Development, Validation and Clinical Utility.

Optimal management of heart failure requires accurate risk assessment. Many prognostic risk models have been proposed for patient with chronic and acute heart failure. Methodological critical issues are the data source, the outcome of interest, the choice of variables entering the model, the validation of the model in external population. Up to now, the proposed risk models can be a useful tool to help physician in the clinical decision-making. The availability of big data and of new methods of analysis may lead to developing new models in the future.

Development and Validation of a Predictive Model for Functional Outcome After Stroke Rehabilitation: The Maugeri Model.

BACKGROUND AND PURPOSE: Prediction of outcome after stroke rehabilitation may help clinicians in decision-making and planning rehabilitation care. We developed and validated a predictive tool to estimate the probability of achieving improvement in physical functioning (model 1) and a level of independence requiring no more than supervision (model 2) after stroke rehabilitation. METHODS: The models were derived from 717 patients admitted for stroke rehabilitation. We used multivariable logistic regression analysis to build each model. Then, each model was prospectively validated in 875 patients. RESULTS: Model 1 included age, time from stroke occurrence to rehabilitation admission, admission motor and cognitive Functional Independence Measure scores, and neglect. Model 2 included age, male gender, time since stroke onset, and admission motor and cognitive Functional Independence Measure score. Both models demonstrated excellent discrimination. In the derivation cohort, the area under the curve was 0.883 (95% confidence intervals, 0.858-0.910) for model 1 and 0.913 (95% confidence intervals, 0.884-0.942) for model 2. The Hosmer-Lemeshow χ2 was 4.12 (P=0.249) and 1.20 (P=0.754), respectively. In the validation cohort, the area under the curve was 0.866 (95% confidence intervals, 0.840-0.892) for model 1 and 0.850 (95% confidence intervals, 0.815-0.885) for model 2. The Hosmer-Lemeshow χ2 was 8.86 (P=0.115) and 34.50 (P=0.001), respectively. Both improvement in physical functioning (hazard ratios, 0.43; 0.25-0.71; P=0.001) and a level of independence requiring no more than supervision (hazard ratios, 0.32; 0.14-0.68; P=0.004) were independently associated with improved 4-year survival. A calculator is freely available for download at https://goo.gl/fEAp81. CONCLUSIONS: This study provides researchers and clinicians with an easy-to-use, accurate, and validated predictive tool for potential application in rehabilitation research and stroke management.

Intra-hospital correlations among 30-day mortality rates in 18 different clinical and surgical settings.

OBJECTIVE: To examine whether a correlation exists in hospitals among 30-day mortality rates for different types of hospitalizations. DESIGN: Cross-sectional study of hospital care based on publically available Italian data from the National Outcome Evaluation Program Edition 2015 of the Italian Agency for Regional Health Services. SETTING AND PARTICIPANTS: Patients hospitalized with a diagnosis of congestive heart failure, acute myocardial infarction, chronic renal failure, chronic obstructive pulmonary disease exacerbation, femoral neck fracture, ischemic stroke and non-variceal upper gastrointestinal bleeding, or those who underwent isolated cardiac valve procedure, isolated coronary artery bypass graft surgery, non-ruptured abdominal aortic aneurysm repair and interventions for the following tumors: colon, kidney, brain, lung, stomach, rectal, liver or pancreatic cancer. MAIN OUTCOME MEASURES: Condition-specific 30-day crude and risk-adjusted mortality rates. RESULTS: A total of 808 280 admissions were reported from 844 institutions (median of 4 conditions evaluated per hospital; interquartile range 2-8). Volumes and outcome varied by clinical and surgical conditions across hospitals. Out of 153 pairs of different conditions, 41 were statistically significant in terms of concordance with crude mortality rates and 44 for their adjusted values. The hospital mean percentile rank for 30-day mortality, a composite measure that summarized the multiple indicators, increased significantly alongside number of conditions per hospital with a significant reduction of mortality when most of the studied conditions were treated in the same hospital. CONCLUSIONS: The variability in 30-day mortality rates at hospital level and the correlation between risk mortality rates suggest that there may be common hospital-wide factors influencing short-term mortality.

Functional Gain After Inpatient Stroke Rehabilitation: Correlates and Impact on Long-Term Survival.

BACKGROUND AND PURPOSE: Prediction of functional outcome after stroke rehabilitation (SR) is a growing field of interest. The association between SR and survival still remains elusive. We sought to investigate the factors associated with functional outcome after SR and whether the magnitude of functional improvement achieved with rehabilitation is associated with long-term mortality risk. METHODS: The study population consisted of 722 patients admitted for SR within 90 days of stroke onset, with an admission functional independence measure (FIM) score of <80 points. We used univariable and multivariable linear regression analyses to assess the association between baseline variables and FIM gain and univariable and multivariable Cox analyses to assess the association of FIM gain with long-term mortality. RESULTS: Age (P<0.001), marital status (P=0.003), time from stroke onset to rehabilitation admission (P<0.001), National Institutes of Health Stroke Scale score at rehabilitation admission (P<0.001), and aphasia (P=0.021) were independently associated with FIM gain. The R2 of the model was 0.275. During a median follow-up of 6.17 years, 36.9% of the patients died. At multivariable Cox analysis, age (P<0.0001), coronary heart disease (P=0.018), atrial fibrillation (P=0.042), total cholesterol (P=0.015), and total FIM gain (P<0.0001) were independently associated with mortality. The adjusted hazard ratio for death significantly decreased across tertiles of increasing FIM gain. CONCLUSIONS: Several factors are independently associated with functional gain after SR. Our findings strongly suggest that the magnitude of functional improvement is a powerful predictor of long-term mortality in patients admitted for SR.

Predicting short-term mortality in advanced decompensated heart failure - role of the updated acute decompensated heart failure/N-terminal pro-B-type natriuretic Peptide risk score.

BACKGROUND: The first few months after admission are the most vulnerable period in patients with acute decompensated heart failure (ADHF). METHODS AND RESULTS: We assessed the association of the updated ADHF/N-terminal pro-B-type natriuretic peptide (NT-proBNP) risk score with 90-day and in-hospital mortality in 701 patients admitted with advanced ADHF, defined as severe symptoms of worsening HF, severely depressed left ventricular ejection fraction, and the need for i.v. diuretic and/or inotropic drugs. A total of 15.7% of the patients died within 90 days of admission and 5.2% underwent ventricular assist device (VAD) implantation or urgent heart transplantation (UHT). The C-statistic of the ADHF/NT-proBNP risk score for 90-day mortality was 0.810 (95% CI: 0.769-0.852). Predicted and observed mortality rates were in close agreement. When the composite outcome of death/VAD/UHT at 90 days was considered, the C-statistic decreased to 0.741. During hospitalization, 7.6% of the patients died. The C-statistic for in-hospital mortality was 0.815 (95% CI: 0.761-0.868) and Hosmer-Lemeshow χ(2)=3.71 (P=0.716). The updated ADHF/NT-proBNP risk score outperformed the Acute Decompensated Heart Failure National Registry, the Organized Program to Initiate Lifesaving Treatment in Patients Hospitalized for Heart Failure, and the American Heart Association Get with the Guidelines Program predictive models. CONCLUSIONS: Updated ADHF/NT-proBNP risk score is a valuable tool for predicting short-term mortality in severe ADHF, outperforming existing inpatient predictive models.

Exercise Performance Is a Prognostic Indicator in Elderly Patients With Chronic Heart Failure--Application of Metabolic Exercise Cardiac Kidney Indexes Score.

BACKGROUND: In patients with chronic heart failure (HF) the Metabolic Exercise Cardiac Kidney Indexes (MECKI) score, is a predictor of cardiovascular death and urgent heart transplantation. We investigated the relationship between age, exercise tolerance and the prognostic value of the MECKI score. METHODS AND RESULTS: We analyzed data from 3,794 patients with chronic systolic HF. The primary endpoint was a composite of cardiovascular death and urgent heart transplantation. Older patients had higher prevalence of comorbidities and lower exercise performance compared with younger subjects (peak V̇O2, 925 vs. 1,351 L/min; P<0.0001; V̇E/V̇CO2slope, 33.2 vs. 28.3; P>0.0001). The rate of the primary endpoint was 19% in the highest age quartile and 14% in the lowest quartile. At multivariable analysis, the independent predictors of the primary endpoint were left ventricular ejection fraction (LVEF), eGFR, peak V̇O2, serum Na(+)and the use of ß-blockers in patients aged ≥70 years, and LVEF, eGFR and peak V̇O2in younger subjects. The MECKI risk score increased across age subgroups, but on receiver operating characteristic curve analysis its prognostic power was similar in both patients aged ≥70 and <70 years. CONCLUSIONS: Older patients with HF are a high-risk population with lower exercise performance. The MECKI score increased according to age and maintained its prognostic value also in older patients.

Renal function and peak exercise oxygen consumption in chronic heart failure with reduced left ventricular ejection fraction.

BACKGROUND: Chronic kidney disease is associated with sympathetic activation and muscle abnormalities, which may contribute to decreased exercise capacity. We investigated the correlation of renal function with peak exercise oxygen consumption (V̇O2) in heart failure (HF) patients. METHODS AND RESULTS: We recruited 2,938 systolic HF patients who underwent clinical, laboratory, echocardiographic and cardiopulmonary exercise testing. The patients were stratified according to estimated glomerular filtration rate (eGFR). Mean follow-up was 3.7 years. The primary outcome was a composite of cardiovascular death and urgent heart transplantation at 3 years. On multivariable regression, eGFR was predictor of peakV̇O2(P<0.0001). Other predictors were age, sex, body mass index, HF etiology, NYHA class, atrial fibrillation, resting heart rate, B-type natriuretic peptide, hemoglobin, and treatment. After adjusting for significant covariates, the hazard ratio for primary outcome associated with peakV̇O2<12 ml·kg(-1)·min(-1)was 1.75 (95% confidence interval (CI): 1.06-2.91; P=0.0292) in patients with eGFR ≥60, 1.77 (0.87-3.61; P=0.1141) in those with eGFR of 45-59, and 2.72 (1.01-7.37; P=0.0489) in those with eGFR <45 ml·min(-1)·1.73 m(-2). The area under the receiver-operating characteristic curve for peakV̇O2<12 ml·kg(-1)·min(-1)was 0.63 (95% CI: 0.54-0.71), 0.67 (0.56-0.78), and 0.57 (0.47-0.69), respectively. Testing for interaction was not significant. CONCLUSIONS: Renal dysfunction is correlated with peakV̇O2. A peakV̇O2cutoff of 12 ml·kg(-1)·min(-1)offers limited prognostic information in HF patients with more severely impaired renal function.

Renal dysfunction and accuracy of N-terminal pro-B-type natriuretic peptide in predicting mortality for hospitalized patients with heart failure.

BACKGROUND: Renal dysfunction may confound the clinical interpretation of N-terminal pro-B-type natriuretic peptide (NT-proBNP) concentration. This study investigated whether renal dysfunction influences the prognostic accuracy of NT-proBNP in acute decompensated heart failure (ADHF). METHODS AND RESULTS: We studied 908 ADHF patients. The primary outcome was 12-month mortality. Interaction between estimated glomerular filtration rate (eGFR) and NT-proBNP in predicting mortality was tested with the likelihood ratio test. The patients were classified into 3 eGFR strata: ≥60, 30-59, and <30 ml·min(-1)·1.73 m(-2). Cox models were used to calculate the adjusted hazard ratios (HR) for NT-proBNP, modeled as a dichotomous or categorized variable, within each level of eGFR. NT-proBNP was categorized using optimal cut-offs defined in ROC analysis for each eGFR level. A total of 234 patients (25.8%) died. Testing for interaction was not significant (χ(2)=0.29; P=0.5928). The adjusted HR for NT-proBNP >5,180 pg/ml was 2.09 (P<0.001) in the highest, 1.7 (P<0.001) in the intermediate, and 3.33 (P=0.010) in the lowest eGFR level. The adjusted HR for NT-proBNP above the optimal cut-offs defined on ROC analysis were 1.5 (P=0.239), 2.2 (P<0.001), and 3.24 (P=0.002), respectively. The models incorporating NT-proBNP as a dichotomous or categorized variable had equivalent C-statistics. CONCLUSIONS: There was no evidence of interaction between eGFR and NT-proBNP in predicting mortality. The NT-proBNP cut-off of 5,180 ng/L provided independent prognostic information, irrespective of the level of residual renal function.

Combined use of high-sensitivity C-reactive protein and N-terminal pro-B-type natriuretic peptide for risk stratification of vascular surgery patients.

BACKGROUND: We sought to assess whether high-sensitivity C-reactive protein (hs-CRP) and pro-B-type natriuretic peptide (NT-proBNP) improve risk prediction when added to an established predictive tool and develop a point-based risk score. METHODS: Four hundred eleven vascular surgery patients were enrolled. The primary outcome was a composite of death, acute coronary syndromes, pulmonary edema within 30 days of surgery, and postoperative troponin-I elevation. The risk score was developed from a logistic regression model by using an integer-based scoring system. RESULTS: The rate of the primary outcome was 18%. Adding both hs-CRP and NT-proBNP to the Revised Cardiac Risk Index led to an increase in C statistic from 0.670 to 0.774. The net reclassification improvement was 0.210 (P = 0.004) and the integrated discrimination improvement was 0.112 (P = 0.0001). In the multivariable regression analysis used to develop the risk score, insulin therapy for diabetes (odds ratio [OR]: 2.8; P = 0.003), open surgery (OR: 1.95; P = 0.027), fibrinogen >377 mg/dL (OR: 2.83; P = 0.001), hs-CRP >3.2 mg/L (OR: 3.85; P < 0.0001), and NT-proBNP >221 ng/L (OR: 4.05; P < 0.0001) were associated with the primary outcome. There was no statistical evidence of overfit. The C index was 0.82 and the Hosmer-Lemeshow statistic was 1.61 (P = 0.0447). The observed and predicted rates of the primary outcome across quartiles of risk score were highly correlated. CONCLUSIONS: Hs-CRP and NT-proBNP substantially improve risk prediction when added to an established predictive tool. The biochemical marker-based risk score may be useful for accurately risk-stratifying vascular surgery patients; nonetheless, further validation studies on external datasets are needed before it can be used in clinical practice.

Incremental prognostic value of functional impairment assessed by 6-min walking test for the prediction of mortality in heart failure.

Natriuretic peptides (NP) are recognized as the most powerful predictors of adverse outcomes in heart failure (HF). We hypothesized that a measure of functional limitation, as assessed by 6-min walking test (6MWT), would improve the accuracy of a prognostic model incorporating a NP. This was a multicenter observational retrospective study. We studied the prognostic value of severe functional impairment (SFI), defined as the inability to perform a 6MWT or a distance walked during a 6MWT < 300 m, in 1696 patients with HF admitted to cardiac rehabilitation. The primary outcome was 1-year all-cause mortality. After adjusting for the baseline multivariable risk model-including age, sex, systolic blood pressure, anemia, renal dysfunction, sodium level, and NT-proBNP-or for the MAGGIC score, SFI had an odds ratio of 2.58 (95% CI 1.72-3.88; p < 0.001) and 3.12 (95% CI 2.16-4.52; p < 0.001), respectively. Adding SFI to the baseline risk model or the MAGGIC score yielded a significant improvement in discrimination and risk classification. Our data suggest that a simple, 6MWT-derived measure of SFI is a strong predictor of death and provide incremental prognostic information over well-established risk markers in HF, including NP, and the MAGGIC score.

What about chronotropic incompetence in heart failure with mildly reduced ejection fraction? Clinical and prognostic implications from the Metabolic Exercise combined with Cardiac and Kidney Indexes score dataset.

AIMS: Chronotropic incompetence (CI) is a strong predictor of outcome in heart failure with reduced ejection fraction, however no data on its clinical and prognostic impacts in heart failure with mildly reduced ejection fraction (HFmrEF) are available. Therefore, the study aims to investigate, in a large multicentre HFmrEF cohort, the prevalence of CI as well as its relationship with exercise capacity and its prognostic role over the cardiopulmonary exercise testing (CPET) parameters. METHODS AND RESULTS: Within the Metabolic Exercise combined with Cardiac and Kidney Indexes (MECKI) database, we analysed data of 864 HFmrEF out of 1164 stable outpatients who performed a maximal CPET at the cycle ergometer and who had no significant rhythm disorders or comorbidities. The primary study endpoint was cardiovascular (CV) death. All-cause death was also explored. Chronotropic incompetence prevalence differed depending on the method (peak heart rate, pHR% vs. pHR reserve, pHRR%) and the cut-off adopted (pHR% from ≤75% to ≤60% and pHRR% ≤ 65% to ≤50%), ranging from 11% to 62%. A total of 84 (9.7%) CV deaths were collected, with 39 (4.5%) occurring within 5 years. At multivariate analysis, both pHR% [hazard ratio 0.97 (0.95-0.99), P < 0.05] and pHRR% [hazard ratio 0.977 (0.961-0.993), P < 0.01] were associated with the primary endpoint. A pHR% ≤ 75% and a pHRR% ≤ 50% represented the most accurate cut-off values in predicting the outcome. CONCLUSION: The study suggests an association between blunted exercise-HR response, functional capacity, and CV death risk among patients with HFmrEF. Whether the CI presence might be adopted in daily HFmrEF management needs to be addressed in larger prospective studies.

Chronotropic incompetence is an easy-to-obtain additive parameter for cardiovascular death risk stratification in heart failure with mildly reduced ejection fraction (HFmrEF). Peak heart rate and peak heart rate reserve are associated with exercise capacity in HFmrEF. Peak heart rate and peak heart rate reserve are associated with cardiovascular death in HFmrEF.