Regional differences in heart failure hospitalizations, mortality, and readmissions in Slovenia 2004-2012.

AIMS: Heart failure (HF) burden is displaying significant inter-regional differences within Europe and within countries. Due to limited data focusing on regional differences, our aim was to evaluate HF hospitalizations, readmissions, and mortality burden in Slovenian statistical regions. METHODS AND RESULTS: The Slovenian National Hospitalization Discharge Registry was searched for HF hospitalizations in patients 20 years or over in the period 2004-12. Annual sex and age-standardized HF hospitalizations, mortality, and HF readmissions rates were calculated for Slovenia and for each Slovenian statistical region. Trends were evaluated using ANOVA. Multiple mixed effect logistic regression models, which included statistical region, admission year, sex, age, intensive care unit treatment, and co-morbidities as a fixed effect and hospital identifier as a random effect, were calculated for mortality and readmissions. Overall, 156 859 HF hospitalizations (55 522 where HF was coded as a main diagnosis and 43 606 as first HF hospitalizations) were recorded. Annual standardized rates varied considerably between statistical regions for main (220-511) and first HF hospitalization (392-721), 30 day (12.6-27.1) and 1 year mortality (66-117), and 30 day (31-80.8) and 1 year readmission (99-24) (per 100 000 patient years in 2012). Yearly decline in HF hospitalization rates was seen for national main (3.6; 0.001) and first (8.4; 0.083) HF hospitalizations, while individual regional main and first HF hospitalization trends mostly did not reach statistical significance. No relevant differences in mortality and readmission endpoints for statistical regions were seen when adjusted for patient demographics and specific co-morbidities. CONCLUSIONS: Significant regional differences in standardized HF hospitalization, mortality, and readmissions between the regions were seen. There were no differences in mortality and readmissions between statistical regions for individual similar patients.

Heart failure prevalence in the general population: SOBOTA-HF study rationale and design.

AIMS: Epidemiological heart failure (HF) data in the era of natriuretic peptides and echocardiography are scarce. The primary aim of this study is to evaluate the HF prevalence in the general population. We will also investigate natriuretic peptide cut-off for diagnosis of HF. Finally, we will be able to identify left ventricular function phenotypes and study relations between cardiac function, clinical presentation, and health-related quality of life. METHODS AND RESULTS: Screening Of adult urBan pOpulation To diAgnose Heart Failure (SOBOTA-HF) is a cross-sectional prevalence study in a representative sample of Murska Sobota residents aged 55 years or more. Individuals will be invited to attend screening visit with point-of-care N-terminal pro-b-type natriuretic peptide (NT-proBNP) testing. All subjects with NT-proBNP ≥ 125 pg/mL will be invited for a diagnostic visit that will include history and physical examination, electrocardiogram, echocardiography, blood and urine sampling, ankle brachial index, pulmonary function tests, body composition measurement, physical performance tests, and questionnaires. To validate the screening procedure, a control group (NT-proBNP < 125 pg/mL) will undergo the same diagnostic evaluation. An external centre will validate echocardiography results, and the HF diagnosis will be adjudicated within an international HF expert panel. Overall and age-specific HF prevalence will be calculated in individuals ≥ 55 years and extrapolated to the whole population. CONCLUSIONS: The SOBOTA-HF study will test the latest HF guideline diagnostic criteria in the general population sample. Next to HF prevalence, it will provide insight into left ventricular function and general patient phenotype; we will also extend current understanding of natriuretic peptides for HF screening.

Increased Myogenic and Protein Turnover Signaling in Skeletal Muscle of Chronic Obstructive Pulmonary Disease Patients With Sarcopenia.

BACKGROUND: Sarcopenia was recently recognized as an independent condition by an International Classification of Diseases, Tenth Revision, Clinical Modification code, and is a frequently observed comorbidity in chronic obstructive pulmonary disease (COPD). Muscle mass is primarily dictated by the balance between protein degradation and synthesis, but their relative contribution to sarcopenia is unclear. OBJECTIVE: We aimed to assess potential differential molecular regulation of protein degradation and synthesis, as well as myogenesis, in the skeletal muscle of COPD patients with and without sarcopenia. METHODS: Muscle biopsies were obtained from the vastus lateralis muscle. Patients with COPD were clustered based on sarcopenia defined by low appendicular skeletal muscle mass index (nonsarcopenic COPD, n = 53; sarcopenic COPD, n = 39), and compared with healthy nonsarcopenic controls (n = 13). The mRNA and protein expression of regulators and mediators of ubiquitin-proteasome system (UPS), autophagy-lysosome system (autophagy), and protein synthesis were analyzed. Furthermore, mRNA expression of myogenesis markers was assessed. RESULTS: UPS signaling was unaltered, whereas indices of UPS regulation (eg, FOXO1 protein; p-FOXO3/FOXO3), autophagy signaling (eg, LC3BII/I; p-ULK1[Ser757]/ULK1), and protein synthesis signaling (eg, AKT1; p-GSK3B/GSK3B; p-4E-BP1/4E-BP1) were increased in COPD. These alterations were even more pronounced in COPD patients with sarcopenia (eg, FOXO1 protein; p-FOXO1/FOXO1; LC3BII/I; p-ULK(Ser555); p-AKT1/AKT1; AKT1; p-4E-BP1). Furthermore, myogenic signaling (eg, MYOG) was increased in COPD despite a concomitant increase of myostatin (MSTN) mRNA expression, with no difference between sarcopenic and nonsarcopenic COPD patients. CONCLUSION: Together with elevated myogenic signaling, the increase in muscle protein turnover signaling in COPD, which is even more prominent in COPD patients with sarcopenia, reflects molecular alterations associated with muscle repair and remodeling.

Echocardiography and cardiac biomarkers in patients with non-small cell lung cancer treated with platinum-based chemotherapy.

BACKGROUND: Non-small cell lung cancer (NSCLC) is the most common type of lung cancer and remains an important cause of cancer death worldwide. Platinum-based chemotherapy (PBC) for NSCLC can modify outcome while the risk of cardiotoxicity remains poorly researched. We aimed to evaluate the incidence and severity of cardiac injury during PBC in patients with NSCLC and to identify patients at risk. METHODS: This was a single-centre, prospective, observational study of patients with early and advanced stage NSCLC referred for PBC. In addition to standard care, patients were examined and evaluated for cardiotoxicity before the first dose (visit 1), at the last dose (visit 2) and 6 months after the last dose of PBC (visit 3). Cardiotoxicity (at visit 2 and 3) was defined as increase in the ultrasensitive troponin T, N-terminal pro-B type natriuretic peptide or decrease in left ventricular ejection fraction (LVEF). RESULTS: Overall, 41 patients (mean age 61 ± 9; 54% men; 68% advanced lung cancer) were included. The median number of PBC cycles was 4. During the study period, there were no incidents of heart failure, and 3 deaths caused by tumour progression were recorded. The mean values of biomarkers and LVEF did not change significantly (p > 0.20). However, 10 (25%) had cardiotoxicity which was independently associated with a history of ischemic heart disease (p = 0.026). CONCLUSIONS: In NSCLC, cardiac assessment and lifestyle modifications may be pursued in patients with a history of cardiac disease and in patients with longer life expectancy.

Mortality and readmissions in heart failure: an analysis of 36,824 elderly patients from the Slovenian national hospitalization database.

BACKGROUND: In heart failure (HF), comorbidity burden and prognostic risks increase with age. Studies investigating outcome in elderly patients from large datasets are lacking, particularly in central and eastern European countries. We analyzed the Slovenian data on mortality and readmissions after first HF hospitalization in patients aged 65 years or over. METHODS: In this observational epidemiological study, the Slovenian national hospitalization database was searched for HF patients aged ≥65 years with first HF hospitalization between 2008 and 2012. All-cause mortality and readmissions were compared in young-olds (65-74 years), middle-olds (75-84 years), and old-olds (≥85 years) using cumulative probability plots and log rank test. The prognostic value of comorbidities on mortality and readmissions for age groups were assessed using multiple Cox proportional hazards models. RESULTS: Overall, 36,824 patients were included (median age 80 years, 41 % men, 20 % in-hospital mortality). The proportions of young-olds, middle-olds, and old-olds were 26, 48, and 26 %, respectively. Arterial hypertension (60 %), pulmonary disease (44 %), and atrial fibrillation (38 %) were the most prevalent comorbidities, with little variation over age. While age group was associated with higher mortality (P < 0.001), no such associations were seen for readmissions at any time points (P > 0.1 for all). Importance of comorbidities as a predictor for mortality faded with increasing age while only small decrease in hazard ratios for readmissions were seen. CONCLUSIONS: Age is an independent predictor of mortality but not readmissions in elderly patients with first HF hospitalization. Comorbidities are important predictors for mortality and readmissions in elderly.

National trends in heart failure hospitalization rates in Slovenia 2004-2012.

AIMS: Heart failure (HF) hospitalization rates are decreasing in western Europe, but little is known about trends in central and east European countries. We analysed the Slovenian national hospitalization database to determine the burden of HF hospitalization. METHODS AND RESULTS: The Slovenian National Hospital Discharge Registry was searched for HF hospitalizations between 2004 and 2012 in patients aged ≥20 years. A total of 55 531 main HF hospitalizations (43 636 first HF hospitalizations) in 34 406 patients (median age 78 years, 55% female) were recorded. The most common co-morbidities were arterial hypertension (54.3%), atrial fibrillation (40.6%), diabetes mellitus (24.5%), and ischaemic heart disease (21.9%). The number of age-standardized main and first HF hospitalizations per 100 000 population decreased from 249 to 232 (7.1%, P = 0.002) and from 467 to 435 (6.8%, P = 0.074), respectively. Crude main and first HF hospitalization rates increased from 249 to 298 (19.8%, P < 0.001) and from 530 to 558 (5.4%, P = 0.100), respectively. After a first HF hospitalization, any HF readmission rates within 30, 60, and 90 days and at 1 year were 11.7, 17.2, 20.9, and 37.5%, respectively. Hospitalization trends were similar in both sexes and across all age groups. In a multivariate log binomial regression model, myocardial infarction, chronic kidney disease, diabetes mellitus, male sex, and year of admission were independently associated with higher HF readmission rates (P < 0.01 for all). CONCLUSIONS: In Slovenia, standardized HF hospitalization rates have decreased but the crude HF hospitalization burden has increased. Readmissions were associated with established cardiovascular risk factors.

Sarcopenia in Advanced COPD Affects Cardiometabolic Risk Reduction by Short-Term High-intensity Pulmonary Rehabilitation.

OBJECTIVES: Sarcopenia is common in chronic obstructive pulmonary disease (COPD) and may contribute to increased cardiometabolic risk. Interventions to reduce cardiometabolic risk in advanced COPD have been scarcely studied. We have investigated the cardiometabolic effect of a short-term high-intensity rehabilitation program in sarcopenic and nonsarcopenic patients with advanced COPD. DESIGN: Prospective observational study. SETTING: Inpatient 4-week short-term high-intensity pulmonary rehabilitation program at the University Clinic Golnik, Slovenia. PARTICIPANTS: 112 stable COPD patients (66 ± 8 years, 85% GOLD III/IV, 66% men). MEASUREMENTS: Blood biomarkers were assessed at baseline and after rehabilitation. Sarcopenia was assessed at baseline (skeletal muscle index <7.23 kg/m(2) for men and <5.67 kg/m(2) for women, as measured by whole-body dual energy X-ray absorptiometry. Insulin resistance (IR) was defined as homeostasis model assessment of insulin resistance (HOMA-IR) above 2.5. RESULTS: IR and sarcopenia were detected in 59% and 55% of patients, respectively. In contrast to sarcopenic patients, rehabilitation decreased HOMA-IR (2.8 to 1.9, P = .031), fat mass index (10.1 to 9.7 kg/m(2), P = .013), waist circumference (103 to 101 cm, P = .002), and low-density lipoprotein cholesterol (3.2 to 3.0 mmol/L, P = .034) in nonsarcopenic patients. A decrease in total cholesterol levels was observed in both groups. CONCLUSIONS: Sarcopenia affects the modification of cardiometabolic risk markers by short-term high-intensity pulmonary rehabilitation in advanced COPD patients.

Emerging biomarkers in heart failure and cardiac cachexia.

Biomarkers are objective tools with an important role for diagnosis, prognosis and therapy optimization in patients with heart failure (HF). To date, natriuretic peptides are closest to optimal biomarker standards for clinical implications in HF. Therefore, the efforts to identify and test new biomarkers in HF are reasonable and justified. Along the natural history of HF, cardiac cachexia may develop, and once at this stage, patient performance and prognosis is particularly poor. For these reasons, numerous biomarkers reflecting hormonal, inflammatory and oxidative stress pathways have been investigated, but only a few convey relevant information. The complex pathophysiology of HF appears far too complex to be embraced by a single biomarker; thus, a combined approach appears reasonable. With these considerations, we have reviewed the recent developments in the field to highlight key candidates with diagnostic, prognostic and therapy optimization properties, either alone or in combination.