Micronutrient Depletion in Heart Failure: Common, Clinically Relevant and Treatable.

Heart failure (HF) is a chronic condition with many imbalances, including nutritional issues. Next to sarcopenia and cachexia which are clinically evident, micronutrient deficiency is also present in HF. It is involved in HF pathophysiology and has prognostic implications. In general, most widely known micronutrients are depleted in HF, which is associated with symptoms and adverse outcomes. Nutritional intake is important but is not the only factor reducing the micronutrient availability for bodily processes, because absorption, distribution, and patient comorbidity may play a major role. In this context, interventional studies with parenteral micronutrient supplementation provide evidence that normalization of micronutrients is associated with improvement in physical performance and quality of life. Outcome studies are underway and should be reported in the following years.

Androgen status in non-diabetic elderly men with heart failure.

PURPOSE: We aimed at evaluating androgen status (serum testosterone [TT] and estimated free testosterone [eFT]) and its determinants in non-diabetic elderly men with heart failure (HF). Additionally, we investigated its associations with body composition and long-term survival. METHODS: Seventy three non-diabetic men with HF and 20 healthy men aged over 55 years were studied. Echocardiography, 6-min walk test, grip strength, body composition measurement by DEXA method were performed. TT, sex hormone binding globulin, NT-proBNP, and adipokines (adiponectin and leptin) were measured. All-cause mortality was evaluated at six years of follow-up. RESULTS: Androgen status (TT, eFT) was similar in elderly men with HF compared to healthy controls (4.79 ± 1.65 vs. 4.45 ± 1.68 ng/ml and 0.409 ± 0.277 vs. 0.350 ± 0.204 nmol/l, respectively). In HF patients, TT was positively associated with NT-proBNP (r= 0.371, p = 0.001) and adiponectin levels (r = 0.349, p = 0.002), while inverse association was noted with fat mass (r = -0.413, p < 0.001). TT and eFT were independently determined by age, total fat mass and adiponectin levels in elderly men with HF (p < 0.05 for all). Androgen status was not predictor for all-cause mortality at six years of follow-up. CONCLUSIONS: In non-diabetic men with HF, androgen status is not altered and is not predictive of long-term outcome.

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.

Rationale and design of the on-treatment PLAtelet Reactivity-Guided Therapy Modification FOR ST-Segment Elevation Myocardial Infarction (PLATFORM) randomized trial.

OBJECTIVES: The present trial aims at examining whether antiplatelet regimen modification, guided by assessment of the on-treatment platelet reactivity, might result with clinical benefit in moderate to high-risk patients with ST-elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PPCI). BACKGROUND: High platelet reactivity has been associated with an increased rate of ischemic events after PCI. Recent large trials did not show a clinical benefit of platelet reactivity-guided therapy modification in acute coronary syndrome patients treated by PCI. METHODS: PLATFORM is an investigator-initiated, prospective, randomized, parallel-group, controlled clinical trial. Approximately 632 STEMI patients with intermediate to high-risk (RISK-PCI score >3) clinical features undergoing PPCI will be randomly allocated to treatment modification or standard therapy. Low responders to aspirin will receive 200 mg aspirin for 30 days. Low responders to clopidogrel will receive 180 mg ticagrelor for 1 year. The primary end-point is the time to the first composite major adverse cardiovascular events (MACE) including death, nonfatal infarction, stroke, or immediate target vessel revascularization. Key safety end-point is the rate of TIMI major bleeding unrelated to coronary artery bypass graft surgery. Our secondary end-points are individual components of MACE, definite stent thrombosis, total bleeding, and the need for blood transfusions. Patients will be followed-up at 30 days and at 1 year after PPCI. CONCLUSION: PLATFORM will determine whether the platelet reactivity-guided use of ticagrelor in combination with 200 mg aspirin, compared with standard antiplatelet regimen, improves clinical outcome in moderate to high-risk STEMI patients undergoing PPCI. CLINICAL TRIAL REGISTRATION: U.S. National Institutes of Health (NIH) at www.clinicaltrials.gov. ClinicalTrials.gov Identifier: NCT01739556, and Current Controlled Trials at www.controlledtrials.com. International Standard Randomized Controlled Trial Number ISRCTN83081599.

Usefulness of the RISK-PCI score to predict stent thrombosis in patients treated with primary percutaneous coronary intervention for ST-segment elevation myocardial infarction: a substudy of the RISK-PCI trial.

Stent thrombosis (ST) is an important cause of death after primary percutaneous coronary intervention (pPCI). This substudy aimed at evaluating the usefulness of the RISK-PCI score, originally developed for the prediction of 30-day major adverse cardiovascular events, to predict the occurrence of ST after pPCI. We analyzed 1972 consecutive patients who underwent pPCI with stent implantation between February 2007 and December 2009. Early ST (EST), late ST (LST), and cumulative 1-year ST (CST) were the predefined end points. Definite, probable, and possible ST were included. Models discrimination and calibration to predict ST was tested using receiver-operating characteristics curves and the goodness-of-fit (GoF) test. Sensitivity analyses and 1000-resample bootstrapping were used to evaluate the model's performance. The rates of EST, LST, and CST were 4.6, 1.4, and 6.0 %, respectively. Compared with controls, the cumulative ST group was associated with much higher rates of adverse clinical outcomes at 30-day follow-up (adjusted odds ratio (OR) for death 6.45, adjusted OR for major bleeding 4.41) and at 12-month follow-up (adjusted OR for death 7.35, adjusted OR for major bleeding 4.56). Internal validation confirmed a reasonably good discrimination and calibration of the RISK-PCI score for the prediction of EST (area under the curve (AUC) 0.71, GoF 0.42), LST (AUC 0.69, GoF 0.36), and CST (AUC 0.70, GoF 0.22) after pPCI. ST after pPCI is associated with adverse 30-day and 1-year clinical outcomes. We conclude that the risk of ST could be accurately assessed using the RISK-PCI score, which might help in deciding upon measures aimed at preventing adverse prognosis.

Anti-Inflammatory Effects of Lipid-Lowering Drugs and Supplements-A Narrative Review.

Cardiovascular diseases (CVD) are the leading cause of death worldwide. Since the establishment of the "lipid hypothesis", according to which, cholesterol level is directly correlated to the risk of CVD, many different lipid-lowering agents have been introduced in clinical practice. A majority of these drugs, in addition to their lipid-lowering properties, may also exhibit some anti-inflammatory and immunomodulatory activities. This hypothesis was based on the observation that a decrease in lipid levels occurs along with a decrease in inflammation. Insufficient reduction in the inflammation during treatment with lipid-lowering drugs could be one of the explanations for treatment failure and recurrent CVD events. Thus, the aim of this narrative review was to evaluate the anti-inflammatory properties of currently available lipid-lowering medications including statins, ezetimibe, bile acid sequestrants (BAS), proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors, fibrates, omega-3 fatty acids, and niacin, as well as dietary supplements and novel drugs used in modern times.

Bone in heart failure.

There is an increasing interest in osteoporosis and reduced bone mineral density affecting not only post-menopausal women but also men, particularly with coexisting chronic diseases. Bone status in patients with stable chronic heart failure (HF) has been rarely studied so far. HF and osteoporosis are highly prevalent aging-related syndromes that exact a huge impact on society. Both disorders are common causes of loss of function and independence, and of prolonged hospitalizations, presenting a heavy burden on the health care system. The most devastating complication of osteoporosis is hip fracture, which is associated with high mortality risk and among those who survive, leads to a loss of function and independence often necessitating admission to long-term care. Current HF guidelines do not suggest screening methods or patient education in terms of osteoporosis or osteoporotic fracture. This review may serve as a solid base to discuss the need for bone health evaluation in HF patients.

The ß-blocker uptitration in elderly with heart failure regarding biomarker levels: CIBIS-ELD substudy.

AIM: We investigated if the baseline value of mid-regional pro-atrial natriuretic peptide (NP), N-terminal pro-B-type NP and copeptin may be helpful in optimizing ß-blocker uptitration in elderly patients with heart failure. PATIENTS & METHODS: According to the biomarkers' levels, 457 patients were divided into three subgroups and compared with each other at baseline and 3 months after. RESULTS: All mid-regional pro-atrial NP and N-terminal pro-B-type NP subgroups had significant amelioration of left ventricle ejection fraction and New York Heart Association (NYHA) class after 3 months of ß-blocker uptitration (p < 0.001). More prominent improvement of left ventricle ejection fraction and New York Heart Association class was observed in subgroups with lower versus higher NPs levels. CONCLUSION: NPs levels, unlike copeptin levels, might be useful tool for objective selection of elderly heart failure patients who could have the greatest benefit of forced uptitration.

Prognostic performance of serial in-hospital measurements of copeptin and multiple novel biomarkers among patients with worsening heart failure: results from the MOLITOR study.

AIMS: In heart failure, various biomarkers are established for diagnosis and risk stratification; however, little is known about the relevance of serial measurements during an episode worsening heart failure (WHF). This study sought to investigate the trajectory of natriuretic peptides and multiple novel biomarkers during hospitalization for WHF and to determine the best time point to predict outcome. METHODS AND RESULTS: MOLITOR (Impact of Therapy Optimisation on the Level of Biomarkers in Patients with Acute and Decompensated Chronic Heart Failure) was an eight-centre prospective study of 164 patients hospitalized with a primary diagnosis of WHF. C-terminal fragment of pre-pro-vasopressin (copeptin), N-terminal pro-B-type natriuretic peptide (NT-proBNP), mid-regional pro-atrial natriuretic peptide (MR-proANP), mid-regional pro-adrenomedullin (MR-proADM), and C-terminal pro-endothelin-1 (CT-proET1) were measured on admission, after 24, 48, and 72 h, and every 72 h thereafter, at discharge and follow-up visits. Their performance to predict all-cause mortality and rehospitalization at 90 days was compared. All biomarkers decreased during recompensation (P < 0.05) except MR-proADM. Copeptin at admission was the best predictor of 90 day mortality or rehospitalization (χ2  = 16.63, C-index = 0.724, P < 0.001), followed by NT-proBNP (χ2  = 10.53, C-index = 0.646, P = 0.001), MR-proADM (χ2  = 9.29, C-index = 0.686, P = 0.002), MR-proANP (χ2  = 8.75, C-index = 0.631, P = 0.003), and CT-proET1 (χ2  = 6.60, C-index = 0.64, P = 0.010). Re-measurement of copeptin at 72 h and of NT-proBNP at 48 h increased prognostic value (χ2  = 23.48, C-index = 0.718, P = 0.00001; χ2  = 14.23, C-index = 0.650, P = 0.00081, respectively). CONCLUSIONS: This largest sample of serial measurements of multiple biomarkers in WHF found copeptin at admission with re-measurement at 72 h to be the best predictor of 90 day mortality and rehospitalization.

Procalcitonin in heart failure: hic et nunc.

Although procalcitonin (PCT) was evaluated for the first time in the setting of heart failure (HF) in 1999, its utility in HF patients is still under examination. Patients with HF have significantly higher plasma PCT concentrations than healthy subjects and PCT levels are associated with severity of HF. It has been confirmed that higher levels of PCT are associated with worse outcomes, such as increased mortality and higher rate of rehospitalization, in HF patients with no evidence of infection. Furthermore, it has been approved that PCT-guided antibiotic treatment in HF patients reduces duration of antibiotic therapy and improves outcomes. This review summarizes current evidence from the published literature of the usefulness and limitations of PCT as a biomarker in HF.

Heart failure management in the elderly - a public health challenge.

Heart failure (HF) is a rapidly growing public health problem and the leading cause of morbidity, mortality, and hospitalization in populations > 65 years. The elderly HF patients have an increased prevalence of HF with preserved ejection fraction and comorbidities, may present with atypical symptoms and signs, have a higher risk for adverse drug reactions, and worse prognosis as compared with younger patients. Moreover, there is a lack of evidence-based therapies for this population because they are underrepresented in the clinical trials. The elderly are less likely to be evaluated by a cardiologist and to be treated in accordance with recommendations of the current HF guidelines. Although the treatment is improving, it is still suboptimal; therefore, HF in elderly patients requires mobilization of public health services and improvement of treatment strategies.

Sex-related analysis of short- and long-term clinical outcomes and bleeding among patients treated with primary percutaneous coronary intervention: an evaluation of the RISK-PCI data.

BACKGROUND: Unfavourable effect of female sex on short- and long-term clinical outcomes has been demonstrated in unselected ST-elevation acute myocardial infarction (STEMI) patients; the results are conflicting in patients who undergo primary percutaneous coronary intervention (PPCI). The objective of this substudy was to determine whether there are sex-related differences in the 30-day and 1-year clinical outcomes and bleeding after PPCI for STEMI. METHODS: We analyzed 2096 STEMI patients enrolled in the Risk Scoring Model to Predict Net Adverse Cardiovascular Outcomes After Primary Percutaneous Coronary Intervention (RISK-PCI) trial from February 2006 to December 2009. Composite efficacy end point comprised all-cause mortality, nonfatal infarction, and stroke. Safety end point was bleeding classified according to the Thrombolysis in Myocardial Infarction (TIMI) criteria. Net adverse cardiovascular events included composite efficacy end point and total bleeding. RESULTS: Women in our study were older and presented later than men. After adjustment for potential confounders, there was no difference between sexes with respect to the composite efficacy end point. A higher rate of total bleeding was observed in women (adjusted odds ratio [OR], 1.67; 95% confidence interval [CI], 1.07-2.61 at 30 days, adjusted OR, 1.63; 95% CI, 1.08-2.47 at 1 year) compared with men. Total bleeding was associated with increased mortality at 30 days (OR, 4.87; 95% CI, 2.79-8.47) and at 1 year (OR, 4.43; 95% CI, 2.79-7.02) after PPCI. CONCLUSIONS: We did not find a significant sex-related difference with respect to the composite efficacy end point. Women had a higher rate of total bleeding which was associated with increased short- and long-term mortality. Specific measures aimed at preventing bleeding in women might improve the prognosis of PPCI patients.

[Possibilities of fast track surgery principles in the treatment of congenital urological anomalies].

INTRODUCTION: Urogenital congenital anomalies are among the most common congenital anomalies and very frequent pathology in paediatric urology. Health care systems strive to shorten the duration and reduce the costs of hospitalization, while maintaining treatment effectiveness. OBJECTIVE: To evaluate the duration of hospital stay of surgically treated patients with congenital urogenital anomalies and estimate the possibility of using fast track surgery principles in paediatric urology in the local settings of a developing country. METHODS: Retrospective non-randomized study included 552 patients who had been surgically treated at the Urology Department of the University Children's Hospital, during 2010. In line with their congenital anomalies, all patients were classified in one of four groups: I--upper urinary tract anomalies (252 patients); II--genital anomalies (164 patients); III--testicular anomalies (76 patients) and IV--associated anomalies (60 patients). We analyzed the total duration of stay as well as pre- and post-operative stay in the hospital. RESULTS: The average duration of hospitalization was 4.7 +/- 4.0 days. Patients with testicular anomalies stayed for the shortest period (2.3 +/- 1.9 days) (p < 0.01) and patients with associated anomalies stayed in the hospital the longest (6.5 +/- 4.7 days) (p < 0.01). CONCLUSION: Modern methods of surgical treatment allow reduction of hospitalization, financial savings to the healthcare system and greater comfort for patients. Our results showed that this is also possible to apply in our environment.