Validation of Perioperative Troponin Levels for Predicting Postoperative Mortality and Long-Term Survival in Patients Undergoing Surgery for Hepatobiliary and Pancreatic Cancer.

Background: Hepatopancreato and biliary (HPB) tumors represent some of the leading cancer-related causes of death worldwide, with the majority of patients undergoing surgery in the context of a multimodal treatment strategy. Consequently, the implementation of an accurate risk stratification tool is crucial to facilitate informed consent, along with clinical decision making, and to compare surgical outcomes among different healthcare providers for either service evaluation or clinical audit. Perioperative troponin levels have been proposed as a feasible and easy-to-use tool in order to evaluate the risk of postoperative myocardial injury and 30-day mortality. The purpose of the present study is to validate the perioperative troponin levels as a prognostic factor regarding postoperative myocardial injury and 30-day mortality in Greek adult patients undergoing HPB surgery. Method: In total, 195 patients undergoing surgery performed by a single surgical team in a single tertiary hospital (2020-2022) were included. Perioperative levels of troponin before surgery and at 24 and 48 h postoperatively were assessed. Model accuracy was assessed by observed-to-expected (O:E) ratios, and area under the receiver operating characteristic curve (AUC). Survival at one year postoperatively was compared between patients with high and normal TnT levels at 24 h postoperatively. Results: Thirteen patients (6.6%) died within 30 days of surgery. TnT levels at 24 h postoperatively were associated with excellent discrimination and provided the best-performing calibration. Patients with normal TnT levels at 24 h postoperatively were associated with higher long-term survival compared to those with high TnT levels. Conclusions: TnT at 24 h postoperatively is an efficient risk assessment tool that should be implemented in the perioperative pathway of patients undergoing surgery for HPB cancer.

Pharmacological Treatments in Heart Failure With Mildly Reduced and Preserved Ejection Fraction: Systematic Review and Network Meta-Analysis.

BACKGROUND: Medical treatment for heart failure with preserved ejection (HFpEF) and heart failure with mildly reduced ejection fraction (HFmrEF) has weaker evidence compared with reduced ejection fraction, despite recent trials with an angiotensin receptor neprilysin inhibitor (ARNI) and sodium glucose co-transporter 2 inhibitors (SGLT2is). OBJECTIVES: The authors aimed to estimate the aggregate therapeutic benefit of drugs for HFmrEF and HFpEF. METHODS: The authors performed a systematic review of MEDLINE, CENTRAL, and Web of Science for randomized trials including patients with heart failure (HF) and left ventricular ejection fraction (LVEF) >40%, treated with angiotensin-converting enzyme inhibitors or angiotensin receptor blockers (analyzed together as renin-angiotensin system inhibitors [RASi]), beta-blockers (BBs), mineralocorticoid receptor antagonists (MRAs), digoxin, ARNI, and SGLT2i. An additive component network meta-analysis was performed. The primary outcome was a composite of cardiovascular (CV) death and first hospitalization for heart failure (HHF); secondary outcomes were CV death, total HHF, and all-cause mortality. RESULTS: The authors identified 13 studies with a total of 29,875 patients and a mean LVEF of 56.3% ± 8.7%. ARNI, MRA, and SGLT2i separately, but not RASi, BB, or digoxin, reduced the primary composite outcome compared with placebo. The combination of ARNI, BB, MRA, and SGLT2i was the most effective (HR: 0.47 [95% CI: 0.31-0.70]); this was largely explained by the triple combination of ARNI, MRA, and SGLT2i (HR: 0.56 [95% CI 0.43-0.71]). Results were similar for CV death (HR: 0.63 [95% CI 0.43-0.91] for ARNI, MRA, and SGLT2i) or total HHF (HR: 0.49 [95% CI 0.33-0.71] for ARNI, MRA, and SGLT2i) alone. In a subgroup analysis, only SGLT2i had a consistent benefit among all LVEF subgroups, whereas the triple combination had the greatest benefit in HFmrEF, robust benefit in patients with LVEF 50% to 59%, and a statistically marginal benefit in patients with LVEF ≥60%. CONCLUSIONS: In patients with HF and LVEF>40%, the quadruple combination of ARNI, BB, MRA, and SGLT2i provides the largest reduction in the risk of CV death and HHF; driven by the robust effect of the triple combination of ARNI, MRA, and SGLT2i. The benefit was more pronounced in HFmrEF patients.

The Short-Term Effect of Olive Oil Extract Enriched with Hydroxytyrosol on Cardiovascular Function.

Olive is rich in polyphenols such as hydroxytyrosol (HT) that have antioxidative and anti-inflammatory effects. In this study, we examined the short-term effects of olive oil extract (OE) enriched with HT on left atrial function, left ventricular (LV) function, and arterial elastic properties in patients with chronic coronary artery disease (CAD). Sixty-one patients with chronic CAD were enrolled. This randomized study had a two-period, two-sequence crossover (AB/BA) design. Group AB (n = 32) initially received OE capsules (500 mg) enriched with HT (5 mg) (two capsules/day) for 30 days, and after a wash out of 48 h, placebo for another 30 days. The opposite occurred in Group BA (n = 29). Exclusion criteria included age >70 years, diabetes, anemia, hypertension, liver and thyroid disease, malignancy, autoimmune disease, kidney disease, use of corticosteroids, weight loss, excessive exercise dietary intervention, and use of antioxidant vitamins. Patients underwent echocardiography/Doppler and applanation tonometry applied to radial artery at the beginning and end of the study. No significant change regarding Vmax, Vp, Vmin, E wave, A wave, deceleration time, LV ejection fraction, central aortic systolic and pulse pressure, and augmentation index. However, a trend toward improvement of E/e' (P = .062) and pulse wave velocity (P = .091) was observed. Use of OE enriched with HT for a limited time period was associated with a trend toward improvement of LV diastolic function and aortic elastic properties in chronic CAD patients. Studies of longer duration are needed to delineate the effect of this promising agent on cardiovascular function and outcomes in chronic CAD.

Larissa Heart Failure Risk Score and Mode of Death in Acute Heart Failure: Insights from REALITY-AHF.

Patients with heart failure (HF) patients may die either suddenly (sudden cardiac death/SCD) or progressively from pump failure. The heightened risk of SCD in patients with HF may expedite important decisions about medications or devices. We used the Larissa Heart Failure Risk Score (LHFRS), a validated risk model for all-cause mortality and HF rehospitalization, to investigate the mode of death in 1363 patients enrolled in the Registry Focused on Very Early Presentation and Treatment in Emergency Department of Acute Heart Failure (REALITY-AHF). Cumulative incidence curves were generated using a Fine-Gray competing risk regression, with deaths that were not due to the cause of death of interest as a competing risk. Likewise, the Fine-Gray competing risk regression analysis was used to evaluate the association between each variable and the incidence of each cause of death. The AHEAD score, a well-validated HF risk score ranging from 0 to 5 (atrial fibrillation, anemia, age, renal dysfunction, and diabetes mellitus), was used for the risk adjustment. Patients with LHFRS 2-4 exhibited a significantly higher risk of SCD (HR hazard ratio adjusted for AHEAD score 3.15, 95% confidence interval (CI) (1.30-7.65), p = 0.011) and HF death (adjusted HR for AHEAD score 1.48, 95% CI (1.04-2.09), p = 0.03), compared to those with LHFRS 0,1. Regarding cardiovascular death, patients with higher LHFRS had significantly increased risk compared to those with lower LHFRS (HR 1.44 adjusted for AHEAD score, 95% CI (1.09-1.91), p = 0.01). Lastly, patients with higher LHFRS exhibited a similar risk of non-cardiovascular death compared to those with lower LHFRS (HR 1.44 adjusted for AHEAD score, 95% CI (0.95-2.19), p = 0.087). In conclusion, LHFRS was associated independently with the mode of death in a prospective cohort of hospitalized HF patients.

The Prognostic Role of Spot Urinary Sodium and Chloride in a Cohort of Hospitalized Advanced Heart Failure Patients: A Pilot Study.

Recent studies have demonstrated the prognostic value of spot urinary sodium (UNa+) in acutely decompensated chronic HF (ADCHF) patients. However, data on the prognostic role of UNa+ and spot urinary chloride (UCl-) in patients with advanced HF are limited. In the present prospective pilot study, we examined the predictive value of UNa+ and UCl- concentration at baseline, at 2 h and at 24 h after admission for all-cause mortality and HF rehospitalization up to 3 months post-discharge. Consecutive advanced HF patients (n = 30) admitted with ADCHF and aged > 18 years were included in the study. Loop diuretics were administered based on the natriuresis-guided algorithm recommended by the recent HF guidelines. Exclusion criteria were cardiogenic shock, acute coronary syndrome, estimated glomerular filtration rate < 15 mL/min/1.73 m2, severe hepatic dysfunction (Child-Pugh category C), and sepsis. UNa+ at baseline (Area Under the Curve (AUC) = 0.75, 95% Confidence Interval (CI) (0.58-0.93), p = 0.019) and at 2 h after admission (AUC = 0.80, 95% CI: 0.64-0.96, p = 0.005) showed good and excellent discrimination, respectively. UCl- at 2 h after admission (AUC = 0.75, 95%CI (0.57-0.93), p = 0.017) demonstrated good discrimination. In the multivariate logistic regression analysis, UNa+ at 2 h (p = 0.02) and dose of loop diuretics at admission (p = 0.03) were the only factors independently associated with the study outcome. In conclusion, UNa+ and UCl- may have a prognostic role in hospitalized advanced HF patients.

Lyophilized recombinant human brain natriuretic peptide: A promising therapy in patients with chronic heart failure.

Lyophilized recombinant brain natriuretic peptide (BNP) is an exogenous peptide synthesized by artificial recombination technology, with a similar structure and similar physiological effects with the endogenous natriuretic peptide secreted by the human body. It's main mechanism of action is to increase cyclic guanosine monophosphate by binding with its corresponding receptor in the body, regulating, thus, the imbalance of the vascular system and cardiac hemodynamics, improving the heart's pumping capacity, and inhibiting sympathetic excitability and myocardial remodeling. Moreover, it can promote mitochondrial metabolism and enhance the use of adenosine triphosphate in cardiomyocytes. In the present study, 102 chronic heart failure (HF) patients were randomly assigned to a control and an observation group consisting of 51 patients each. Patients of the control group were treated with standard HF therapy for 3 d including oral metoprolol tartrate tablets, spironolactone, and olmesartanate while patients of the observation group were administered the recombinant human BNP injection for the same time-period, plus the standard HF therapy. The recombinant human BNP group (observation group) demonstrated better physical, emotional, social, and economic scores, as well as cardiac and inflammatory biomarkers such as serum hypersensitive C-reactive protein, N-terminal pro BNP and troponin I levels, compared to the control group. Moreover, cardiac function was also improved, as left ventricular ejection fraction and stroke volume were significantly higher in the observation group than in the control group. Interestingly, adverse reactions were not different between the 2 groups. However, these results are not generalizable and the need of large multicenter randomized controlled trials examining the safety and efficacy of recombinant human BNP in HF patients is of major importance.

Rejection Requiring Treatment within the First Year following Heart Transplantation: The UNOS Insight.

(1) Background: Heart failure is an extremely impactful health issue from both a social and quality-of-life point of view and the rate of patients with this condition is destined to rise in the next few years. Transplantation remains the mainstay of treatment for end-stage heart failure, but a shortage of organs represents a significant problem that prolongs time spent on the waiting list. In view of this, the selection of donor and recipient must be extremely meticulous, considering all factors that could predispose to organ failure. One of the main considerations regarding heart transplants is the risk of graft rejection and the need for immunosuppression therapy to mitigate that risk. In this study, we aimed to assess the characteristics of patients who need immunosuppression treatment for rejection within one year of heart transplantation and its impact on mid-term and long-term mortality. (2) Methods: The United Network for Organ Sharing (UNOS) Registry was queried to identify patients who solely underwent a heart transplant in the US between 2000 and 2021. Patients were divided into two groups according to the need for anti-rejection treatment within one year of heart transplantation. Patients' characteristics in the two groups were assessed, and 1 year and 10 year mortality rates were compared. (3) Results: A total of 43,763 patients underwent isolated heart transplantation in the study period, and 9946 (22.7%) needed anti-rejection treatment in the first year. Patients who required treatment for rejection within one year after transplant were more frequently younger (49 ± 14 vs. 52 ± 14 years, p < 0.001), women (31% vs. 23%, p < 0.001), and had a higher CPRA value (14 ± 26 vs. 11 ± 23, p < 0.001). Also, the rate of prior cardiac surgery was more than double in this group (27% vs. 12%, p < 0.001), while prior LVAD (12% vs. 11%, p < 0.001) and IABP (10% vs. 9%, p < 0.01) were more frequent in patients who did not receive anti-rejection treatment in the first year. Finally, pre-transplantation creatinine was significantly higher in patients who did not need treatment for rejection in the first year (1.4 vs. 1.3, p < 0.01). Most patients who did not require anti-rejection treatment underwent heart transplantation during the new allocation era, while less than half of the patients who required treatment underwent transplantation after the new allocation policy implementation (65% vs. 49%, p < 0.001). Patients who needed rejection treatment in the first year had a higher risk of unadjusted 1 year (HR: 2.25; 95% CI: 1.88-2.70; p < 0.001), 5 year (HR: 1.69; 95% CI: 1.60-1.79; p < 0.001), and 10 year (HR: 1.47; 95% CI: 1.41-1.54, p < 0.001) mortality, and this was confirmed at the adjusted analysis at all three time-points. (4) Conclusions: Medical treatment of acute rejection was associated with significantly increased 1 year mortality compared to patients who did not require anti-rejection therapy. The higher risk of mortality was confirmed at a 10 year follow-up. Further studies and newer follow-up data are required to investigate the role of anti-rejection therapy in the heart transplant population.

Heart failure with preserved ejection fraction: A distinct heart failure phenotype?

The present work discusses the serious confusion resulting from the arbitrary nomenclature of heart failure with preserved ejection fraction (HFpEF), the presumed underlying pathophysiology, and the supposed features. A consequence of this misconception is that HFpEF trials have recruited patients with entirely different characteristics rendering the extrapolation of the results of one study to the other infeasible and dramatically affecting diagnosis and treatment.

COVID-19 and the heart.

An outbreak of coronavirus disease 2019 (COVID-19) occurred in December 2019 due to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which is a strain of SARS-CoV. Patients infected with the virus present a wide spectrum of manifestations ranging from mild flu-like symptoms, cough, fever and fatigue to severe lung injury, appearing as bilateral interstitial pneumonia or acute respiratory failure. Although SARS-CoV-2 infection predominantly offends the respiratory system, it has been associated with several cardiovascular complications as well. For example, patients with COVID-19 may either develop type 2 myocardial infarction due to myocardial oxygen demand and supply imbalance or acute coronary syndrome resulting from excessive inflammatory response to the primary infection. The incidence of COVID-19 related myocarditis is estimated to be accountable for an average of 7% of all COVID-19 related fatal cases, whereas heart failure (HF) may develop due to infiltration of the heart by inflammatory cells, destructive action of pro-inflammatory cytokines, micro-thrombosis and new onset or aggravated endothelial and respiratory failure. Lastly, SARS-CoV-2 can engender arrhythmias through direct myocardial damage causing acute myocarditis or through HF decompensation or secondary, through respiratory failure or severe respiratory distress syndrome. In this comprehensive review we summarize the COVID-19 related cardiovascular complications (acute coronary syndromes, myocarditis, HF, arrhythmias) and discuss the main underlying pathophysiological mechanisms.

Post-Implant Phosphodiesterase-5 Inhibitors in Patients with Left Ventricular Assist Device: A Systematic Review and Meta-Analysis.

Background: Despite the improvement in left ventricular assist device (LVAD) technology and the advent of third-generation LVADs, hemocompatibility-related events remain a significant issue. Therefore, new pharmacological treatments are necessary to optimize patient management and to further reduce hemocompatibility-related events. The purpose of the present systematic review and meta-analysis was to summarize the existing data regarding the safety and efficacy of post-implant phosphodiesterase-5 inhibitors (PDE-5i) on hemocompatibility-related events. Methods: Among the 258 articles in Pubmed, Scopus, and CENTRAL that were retrieved (1990−2022), 15 studies were included in the qualitative synthesis, and 9 studies were included in the quantitative synthesis. The fixed-effects model was used because it is statistically sound for combining a very small number of studies. The primary endpoint of the study was all-cause mortality, whereas the secondary endpoints were ischemic stroke, pump thrombosis, and gastrointestinal bleeding. Results: Mortality was significantly lower in the PDE-5i group vs. the control group (OR: 0.92 [95% CI: 0.85, 0.98]; p = 0.02). The secondary endpoints ischemic stroke (OR: 0.87 [95% CI: 0.78, 0.98]; p = 0.02) and pump thrombosis (OR: 0.90 [95% CI: 0.82, 0.99]; p = 0.04) were also lower in the PDE-5i group. The incidence of gastrointestinal bleeding was significantly higher in patients with LVAD receiving PDE-5i (OR: 1.26 [95% CI: 1.11, 1.44]; p < 0.01). In the overall analysis, the heterogeneity of outcomes was low, except for pump thrombosis. Conclusions: The use of PDE-5i post-implant was associated with lower mortality and thrombotic events but with a higher risk of gastrointestinal bleeding.

The effect of SGLT-2i administration on red blood cell distribution width in patients with heart failure and type 2 diabetes mellitus: A randomized study.

Background: Recent studies suggest that the pivotal mechanism of sodium glucose co-transporter-2 inhibitors (SGLT-2i) favorable action in patients with heart failure (HF) and type 2 diabetes mellitus (DM) is the stimulation of erythropoiesis via an early increase in erythropoietin (EPO) production which leads to hematocrit rise. Red blood cell distribution width (RDW) is a simple hematological parameter which reflects the heterogeneity of the red blood cell size (anisocytosis). Since, EPO has been also implicated in the pathophysiology of RDW increase, the current mechanistic study examined the effect of SGLT-2i administration on red blood cells size (RDW) in patients with HF and DM. Methods: The present was a prospective single-center study. Patients (N=110) were randomly assigned to dapagliflozin (10 mg a day on top of antidiabetic treatment) or the control group. Inclusion criteria were: (a) age > 18 years, (b) history of type 2 DM and hospitalization for HF exacerbation within 6 months. The evaluation of patients (at baseline, 6 and 12 months) included clinical assessment, laboratory blood tests, and echocardiography. Data were modeled using mixed linear models with dependent variable the RDW index. In order to find factors independently associated with prognosis (1-year death or HF rehospitalization), multiple logistic regression was conducted with death or HF rehospitalization as dependent variable. Results: An RDW increase both after 6 and after 12 months was observed in the SGLT-2i (dapagliflozin) group (p < 0.001 for all time comparisons), whereas RDW didn't change significantly in the control group. The increase in RDW was positively correlated with EPO, while negatively correlated with ferritin and folic acid (p < 0.005 for all). Baseline RDW was significantly associated with 1-year death or rehospitalization, after adjusting for group (SGLT-2i vs. control), age, gender, smoking and BMI at baseline. Conclusion: RDW increased with time in patients with HF and DM who received SGLT-2i (dapagliflozin). The increased RDW rates in these patients may stem from the induction of hemopoiesis from dapagliflozin. Baseline RDW was found to be independently associated with outcome in patients with HF and DM.

A Holistic View of Advanced Heart Failure.

Advanced heart failure (HF) may occur at any level of left ventricular (LV) ejection fraction (LVEF). The latter, which is widely utilized for the evaluation of LV systolic performance and treatment guidance of HF patients, is heavily influenced by LV size and geometry. As the accurate evaluation of ventricular systolic function and size is crucial in patients with advanced HF, the LVEF should be supplemented or even replaced by more specific indices of LV function such as the systolic strain and cardiac power output and size such as the LV diastolic diameters and volumes. Conventional treatment (cause eradication, medications, devices) is often poorly tolerated and fails and advanced treatment (mechanical circulatory support [MCS], heart transplantation [HTx]) is required. The effectiveness of MCS is heavily dependent on heart size, whereas HTx which is effective in the vast majority of the cases is limited by the small donor pool. Expanding the MCS indications to include patients with small ventricles as well as the HTx donor pool are major challenges in the management of advanced HF.

Heart failure with reduced, mildly reduced, or preserved left ventricular ejection fraction: Has reasoning been lost?

Left ventricular (LV) ejection fraction (LVEF), defined as LV stroke volume divided by end-diastolic volume, has been systematically used for the diagnosis, classification, and management of heart failure (HF) over the last three decades. HF is classified as HF with reduced LVEF, HF with midrange or mildly reduced LVEF, and HF with preserved LVEF using arbitrary, continuously changing LVEF cutoffs. A prerequisite for using this LVEF-based terminology is knowledge of the LVEF normal range, which is lacking and may lead to erroneous conclusions in HF, especially at the higher end of the LVEF spectrum.

Acute Myopericarditis after the Second Dose of mRNA COVID-19 Vaccine Mimicking Acute Coronary Syndrome.

Myocarditis is a rare adverse event of vaccination. Recently, mRNA vaccines for COVID-19 have been reported to correlate with myocarditis, specifically in adolescents and young men. We report a rare case of a 50-year-old man who presented with symptoms of myocardial infarction 3 days after the second dose of vaccination for COVID-19. Cardiac magnetic resonance (CMR) imaging revealed acute myopericarditis. Clinicians should be aware of that rare side effect of mRNA vaccines for COVID-19 that can affect not only younger recipients but also middle-aged patients presenting with symptoms mimicking acute coronary syndrome.

Effectiveness and safety of intracranial events associated with the use of direct oral anticoagulants for atrial fibrillation: A systematic review and meta-analysis of 92 studies.

AIMS: Observational studies have investigated the effectiveness and safety of direct oral anticoagulants (DOACs) and vitamin K antagonists (VKAs) used in nonvalvular atrial fibrillation. We performed a systematic review and meta-analysis assessing the risk of ischaemic stroke, thromboembolism (TE) and intracranial haemorrhage (ICH) associated with the use of DOACs and VKAs. METHODS: Medline and Embase were systematically searched until April 2021. Observational studies were gathered and hazard ratios (HRs) with 95% confidence intervals (CI) were extracted. Subgroup analyses based on DOAC doses, history of chronic kidney disease, stroke, exposure to VKA, age and sex were performed. A random-effects model was used. RESULTS: We included 92 studies and performed 107 comparisons. Apixaban was associated with lower risk of stroke (HR: 0.82, 95% CI: 0.68-0.99) compared to dabigatran. Rivaroxaban was associated with lower risk of stroke (HR: 0.90, 95% CI: 0.83-0.98) compared to VKA. Dabigatran (HR: 0.85, 95% CI: 0.80-0.91), rivaroxaban (HR: 0.83, 95% CI: 0.77-0.89) and apixaban (HR: 0.75, 95% CI: 0.65-0.86) were associated with lower risk for TE/stroke compared to VKA. Apixaban (HR: 1.32, 95% CI: 1.03-1.68) and rivaroxaban (HR: 1.58, 95% CI: 1.31-1.89) were associated with higher risk of ICH compared to dabigatran. Dabigatran (HR: 0.48, 95% CI: 0.44-0.52), apixaban (HR: 0.60, 95% CI: 0.49-0.73) and rivaroxaban (HR: 0.73, 95% CI: 0.65-0.81) were associated with lower risk of ICH compared to VKA. CONCLUSION: Our study demonstrated significant differences in the risk of ischaemic stroke, TE/stroke and ICH associated with individual DOACs compared to both other DOACs and VKA.

The Interventricular Septum: Structure, Function, Dysfunction, and Diseases.

Vertebrates developed pulmonary circulation and septated the heart into venous and arterial compartments, as the adaptation from aquatic to terrestrial life requires more oxygen and energy. The interventricular septum (IVS) accommodates the ventricular portion of the conduction system and contributes to the mechanical function of both ventricles. Conditions or diseases that affect IVS structure and function (e.g., hypertrophy, defects, other) may lead to ventricular pump failure and/or ventricular arrhythmias with grave consequences. IVS structure and function can be evaluated today using current imaging techniques. Effective therapies can be provided in most cases, although definitions of underlying etiologies may not always be easy, particularly in the elderly due to overlap between genetic and acquired causes of IVS hypertrophy, the most common being IVS abnormality. In this review, state-of-the-art information regarding IVS morphology, physiology, physiopathology, and disease is presented.

Glucose lowering does not necessarily reduce cardiovascular risk in type 2 diabetes.

Diabetes mellitus (DM) is a health condition characterized by glucose dysregulation and affects millions of people worldwide. The presentation of heart failure in diabetic cardiomyopathy extends over a wide phenotypic spectrum, commencing from asymptomatic, subclinical structural abnormalities to severely symptomatic biventricular dysfunction with increased mortality risk. Similarly, the spectrum of systolic dysfunction in diabetic-induced heart failure is diverse. DM leads also to cardiac electrical remodeling reacting on various targets. Dipeptidyl peptidase-4 (DPP-4) inhibitors reduce glucagon and blood glucose levels by raising levels of the endogenous hormones glucagon-like-peptide 1 and glucose-dependent insulinotropic peptide and constitute a safe and effective glucose lowering treatment option in patients with type 2 DM. Despite DPP-4 inhibitors' efficacy regarding glycemic control, their effect on cardiovascular outcomes (myocardial infarction, stroke, hospitalization for heart failure, hospitalization for unstable angina, hospitalization for coronary revascularization, and cardiovascular death) in diabetic patients has been neutral. The potential correlation between atrial flutter and DPP-4 inhibitors administration needs further investigation.

Red Blood Cell Distribution Width in Heart Failure: Pathophysiology, Prognostic Role, Controversies and Dilemmas.

Red blood cell distribution width (RDW), an integral parameter of the complete blood count (CBC), has been traditionally used for the classification of several types of anemia. However, over the last decade RDW has been associated with outcome in patients with several cardiovascular diseases including heart failure. The role of RDW in acute, chronic and advanced heart failure is the focus of the present work. Several pathophysiological mechanisms of RDW's increase in heart failure have been proposed (i.e., inflammation, oxidative stress, adrenergic stimulation, undernutrition, ineffective erythropoiesis, reduced iron mobilization, etc.); however, the exact mechanism remains unknown. Although high RDW values at admission and discharge have been associated with adverse prognosis in hospitalized heart failure patients, the prognostic role of in-hospital RDW changes (ΔRDW) remains debatable. RDW has been incorporated in recent heart failure prognostic models. Utilizing RDW as a treatment target in heart failure may be a promising area of research.