Non coding RNA therapeutics in the treatment of heart failure.

ncRNA therapeutics can target either ncRNAs or conventional mRNA, offering both superior pharmacokinetics and selectivity to conventional therapies and addressing new, previously unexplored pathways. Although no ncRNA has yet been approved for the treatment of heart failure, in this review we present 5 most promising pathways and agents that are either in human clinical trials or offer great promise in the near future.

Advanced Respiratory Failure Requiring Tracheostomy-A Marker of Unfavourable Prognosis after Heart Transplantation.

Advanced respiratory failure with tracheostomy requirement is common in heart recipients. The aim of the study is to assess the tracheostomy rate after orthotopic heart transplantation and identify the subgroups of patients with the highest need for tracheostomy and these groups' association with mortality at a single centre through a retrospective analysis of 140 consecutive patients transplanted between December 2012 and July 2018. As many as 28.6% heart recipients suffered from advanced respiratory failure with a need for tracheostomy that was performed after a median time of 11.5 days post-transplant. Tracheostomy was associated with a history of stroke (OR 3.4; 95% CI) 1.32-8.86; p = 0.012), previous sternotomy (OR 2.5; 95% CI 1.18-5.32; p = 0.017), longer cardiopulmonary bypass time (OR 1.01; 95% CI 1.00-1.01; p = 0.007) as well as primary graft failure (OR 6.79; 95% CI2.93-15.71; p < 0.001), need of renal replacement therapy (OR 19.2; 95% 2.53-146; p = 0.004) and daily mean SOFA score up to 72 h (OR 1.50; 95% 1.23-1.71; p < 0.01). One-year mortality was significantly higher in patients requiring a tracheostomy vs. those not requiring one during their hospital stay (50% vs. 16%, p < 0.001). The need for tracheostomy in heart transplant recipients was 30% in our study. Advanced respiratory failure was associated with over 3-fold greater 1-year mortality. Thus, tracheostomy placement may be regarded as a marker of unfavourable prognosis.

Epicardial fat and ventricular arrhythmias.

The arrhythmogenic role of epicardial adipose tissue (EAT) in atrial arrhythmias is well established, but its effect on ventricular arrhythmias has been significantly less investigated. Since ventricular arrhythmias are thought to cause 75%-80% of cases of sudden cardiac death, this is not a trivial issue. We provide an overview of clinical data as well as experimental and molecular data linking EAT to ventricular arrhythmias, attempting to dissect possible mechanisms and indicate future directions of research and possible clinical implications. However, despite a wealth of data indicating the role of epicardial and intramyocardial fat in the induction and propagation of ventricular arrhythmias, unfortunately there is currently no direct evidence that indeed EAT triggers arrhythmia or can be a target for antiarrhythmic strategies.

ARTERIAL HYPEROXIA AND MORTALITY IN PATIENTS UNDERGOING VENOARTERIAL EXTRACORPOREAL MEMBRANE OXYGENATION.

ABSTRACT: Background: Venoarterial extracorporeal membrane oxygenation (VA-ECMO) can easily lead to supranormal oxygenation. The impact of hyperoxygenation beyond the early VA-ECMO support phase is unexplored. We sought to investigate its association with short- and long-term mortality. Methods: A total of 10,615 arterial blood gases of 179 patients undergoing VA-ECMO between 2013 and 2018 in our cardiosurgical tertiary center were analyzed for partial pressure of oxygen (PaO2) and its association with in-hospital, 90-day, and 1-year mortality. Patients were stratified into terciles (T) based on PaO2. Results: The median systemic PaO2 during VA-ECMO was 122 mm Hg (Q1-Q3, 111-158 mm Hg) and was significantly higher in 90-day nonsurvivors versus survivors (134 mm Hg [Q1-Q3, 114-175 mm Hg] vs. 114 mm Hg [Q1-Q3, 109-136 mm Hg]; P < 0.001). The incidence of mortality increased at all time points tested after VA-ECMO implantation along with the increasing terciles of PaO2. The lowest mortality rates were noted for patients with median PaO2 values of <115 mm Hg (T1), whereas patients with median PaO2 values of >144 mm Hg (T3) had the highest mortality rates. Bonferroni multiple testing analysis found the T3 of PaO2 to be a predictor of decreased 90-day survival in comparison with T1 (P < 0.001) and T2 (P = 0.002). Multivariable Cox regression analyses for in-hospital, 90-day, and 1-year mortality showed a significant association of the T3 compared with the T2 and the T1 of PaO2 to mortality across all endpoints. Conclusion: Hyperoxygenation during VA-ECMO might be associated with increased all-cause mortality. The results of our study further document the known toxicity of hyperoxygenation in general critical care patients and mark the need to focus specifically on VA-ECMO patients.

Troponin T and Survival following Cardiac Surgery in Patients Supported with Extracorporeal Membrane Oxygenation for Post-Cardiotomy Shock.

BACKGROUND: While troponin is an established biomarker of cardiac injury, its prognostic significance in post-cardiotomy cardiogenic shock patients supported by venoarterial extracorporeal membrane oxygenation (PCCS-VA-ECMO) remains unclear. OBJECTIVE: This study aimed to assess the correlation between early post-operative troponin T levels and both short-term and long-term mortality outcomes in this cohort. METHODS: We evaluated 1457 troponin T measurements from 102 PCCS-VA-ECMO patients treated from 2013 to 2018 at a specialized cardio-surgical and transplantation center. Emphasis was placed on troponin concentrations at 24-48 h post-surgery, post-VA-ECMO implantation, and peak troponin levels in relation to VA-ECMO weaning, as well as 90-day and one-year mortality. RESULTS: No significant association was observed between troponin T levels post-VA-ECMO implantation and 90-day mortality (median: 1338 ng/L for overall, 1529 ng/L for survivors vs. 1294 ng/L for non-survivors; p = 0.146) or between peak troponin levels and 90-day mortality (median: 3583 ng/L for overall, 3337 ng/L for survivors vs. 3666 ng/L for non-survivors; p = 0.709). Comprehensive multivariate models showed no correlation between troponin levels and various mortality endpoints. Notably, age, procedure urgency, type, LVEF pre-surgery, Euroscore II, prior cardiac arrest, and VA-ECMO duration were not linked with troponin release. Hemodiafiltration emerged as the strongest mortality risk factor [HR 2.4]. CONCLUSIONS: Isolated early Troponin T release and peak troponin T were not associated, while organ complications were linked with VA-ECMO weaning or short- and long-term prognosis. The results underscore the multi-organ implications of PCCS in determining survival.

Clinical and Molecular Aspects of Iron Metabolism in Failing Myocytes.

Heart failure (HF) is a common disease that causes significant limitations on the organism's capacity and, in extreme cases, leads to death. Clinically, iron deficiency (ID) plays an essential role in heart failure by deteriorating the patient's condition and is a prognostic marker indicating poor clinical outcomes. Therefore, in HF patients, supplementation of iron is recommended. However, iron treatment may cause adverse effects by increasing iron-related apoptosis and the production of oxygen radicals, which may cause additional heart damage. Furthermore, many knowledge gaps exist regarding the complex interplay between iron deficiency and heart failure. Here, we describe the current, comprehensive knowledge about the role of the proteins involved in iron metabolism. We will focus on the molecular and clinical aspects of iron deficiency in HF. We believe that summarizing the new advances in the translational and clinical research regarding iron deficiency in heart failure should broaden clinicians' awareness of this comorbidity.

Burden of hospitalizations in newly diagnosed heart failure patients in Poland: real world population based study in years 2013-2019.

AIMS: We aim to report trends in unplanned hospitalizations among newly diagnosed heart failure patients with regard to hospitalizations types and their impact on outcomes. METHODS AND RESULTS: A nation-wide study of all citizens in Poland with newly diagnosed heart failure based on ICD-10 coding who were beneficiaries of either public primary, secondary, or hospital care between 2013 and 2018 in Poland. Between 1 January 2013 and 31 December 2019, there were 1 124 118 newly diagnosed heart failure patients in Poland in both out- and inpatient settings. The median observation time was 946 days. As many as 49% experienced at least one acute heart failure hospitalization. Once hospitalized, 44.6% patients experienced at least one all-cause rehospitalization and 26% another heart failure rehospitalization. The latter had the highest Charlson co-morbidity index (1.36). The 30 day heart failure readmission rate was 2.96%. Kaplan-Meier analysis revealed very early readmissions (up to 1-7 days) were associated with better survival compared with rehospitalization between 8 and 30 days. All-cause mortality was related to the number of hospitalization with adjusted estimated hazard ratios: 1.550 (95% CI: 1.52-158) for the second HF hospitalization, 2.158 (95% CI: 2.098-2.219) for third, and 2.788 (95% CI: 2.67-2.91) for the fourth HF hospitalization and subsequent ones, as compared with the first hospitalization. CONCLUSIONS: Among newly diagnosed heart failure patients in Poland between 2013 and 2019, nearly half required at least one unplanned heart failure hospitalization. The risk of death was growing with every other hospital reoccurrence due to heart failure.

Prognostic significance of serum lactate following cardiac transplantation.

Aim: Hyperlactatemia is common post-heart transplantation. Lactate measurements in the first 24 h were analyzed with respect to mortality. Methods: A total of 153 consecutive cardiac transplant patients were reviewed. Recipients of organs maintained in a state of ex vivo perfusion were included. Results: A total of 143 heart recipients were included. Hyperlactatemia (>2 mmol/l) was present in all patients. Despite maximum lactate and lactate clearance being significantly higher in nonsurvivors (p = 0.002, p = 0.004), neither receiver operator curve analysis nor multivariate logistic regression showed association with 1-year mortality. In comparison, the minimum lactate was significantly associated with mortality (area under the curve 0.728 [p < 0.001]; odds ratio 1.28 [95% 1.01-162; p = 0.04]). Conclusion: The minimum lactate, a surrogate of persistent hyperlactatemia, was demonstrated to be superior compared with maximum lactate and lactate clearance in determining patient prognosis.

Acute kidney injury after transcatheter aortic valve replacement in the elderly: outcomes and risk management.

Aortic stenosis is the most common cause of valve replacement in Europe and North America with prevalence increasing with age. Transcatheter valve replacement (TAVR) represents an alternative for surgical valve replacement of severely stenotic valves. Despite lower risk of acute kidney injury compared to that associated with surgery, this complication remains prevalent in patients undergoing TAVR. There is a paucity of data confirming the relation of acute kidney injury with high morbidity and mortality, especially when superimposed on chronic kidney disease, which is a frequent comorbidity in the elderly with severe aortic stenosis. As there is no consensus on the prevention of acute kidney injury in patients undergoing TAVR, identification and limitation of risk factors are crucial. In this review, we aim to discuss the key aspects of acute kidney injury diagnosis, risk assessment, and outcomes in TAVR patients, and to point out gaps in current knowledge.

Patterns of changes in functional and neurocognitive status in elderly patients after transcatheter vs. surgical aortic valve replacements.

BACKGROUND: Replacement of severely stenotic aortic valve may influence cognitive and physical functioning. The aim of this study was to compare cognitive and functional status after surgical (SAVR) vs. transcatheter aortic valve replacements (TAVR) in the elderly with severe aortic stenosis (AS). METHODS: It was a prospective observational study with over 6 months of follow-up. Eighty ≥70-year-old patients with AS underwent TAVR (N.=40) or SAVR (N.=40). Mini Mental State Exam (MMSE), activities daily living (ADL) score and instrumental activities daily living (IADL) score were used to assess the cognitive status, fundamental functioning and complex independent living skills, respectively. The tests were conducted at baseline and 6 months after the procedure. Additionally, MMSE was carried out at discharge. RESULTS: Baseline MMSE score was lower in the TAVR vs. SAVR group (P=0.001). In the SAVR group, there was a transient in-hospital decline in mean MMSE score (P=0.020), absent in the TAVR group. Baseline ADL and IADL scores were lower in TAVR patients. Both groups experienced mild improvement. The average increase among those with improved IADL score was larger after TAVR (2.37 vs. 1.37 after SAVR; P=0.029). A systolic blood pressure (SBP) decrease <60 mmHg as well as larger periprocedural shift in SBP (expressed by a difference between maximum and minimum SBP) during TAVR were associated with the decline in the ADL (P=0.001) and IADL scores (P=0.043). CONCLUSIONS: Cognitive patterns differed between the TAVR and SAVR patients. A transient MMSE decline did not alter the 6-month status. TAVR might improve functionality. Periprocedural SBP decrease and larger changes in SBP are risk factors for functionality deterioration after TAVR.

Serum beta-2 microglobulin levels for predicting acute kidney injury complicating aortic valve replacement.

OBJECTIVES: Acute kidney injury complicating both transcatheter and surgical aortic valve replacement is associated with high rates of morbidity and mortality. The aim of this study was to investigate the role of serum beta 2 (ß2) microglobulin, cystatin C and neutrophil gelatinase-associated lipocalin levels in detecting periprocedural acute kidney injury. METHODS: Eighty consecutive patients who were 70 years of age or older and who were having surgical (n = 40) or transcatheter (n = 40) aortic valve replacement were recruited in a prospective study. The biomarkers were tested before the procedure, 6 times afterwards, at discharge and at a 6-month follow-up visit. RESULTS: The baseline ß2-microglobulin level was the strongest predictor of acute kidney injury as a complication of transcatheter aortic valve replacement [odds ratio (OR) 5.277, P = 0.009]. Its level 24 h after the procedure reached the largest area under the curve (AUC) of 0.880 (P < 0.001) for detecting acute kidney injury. In multivariate logistic regression analysis, the levels of ß2-microglobulin and cystatin C 24 h after the procedure were significantly associated with acute kidney injury after transcatheter valve replacement (OR 38.15, P = 0.044; OR 1782, P = 0.019, respectively). In the surgical aortic valve replacement group, the highest AUCs belonged to ß2-microglobulin and cystatin C at 24 h (AUC = 0.808, P = 0.003 and AUC = 0.854, P = 0.001, respectively). Their higher values were also associated with acute kidney injury (OR 17.2, P = 0.018; OR 965.6, P = 0.02, respectively). A persistent increase in the postoperative levels of ß2-microglobulin following acute kidney injury was associated with the progression of chronic kidney disease for 6 months after both transcatheter (OR 6.56, P = 0.030) and surgical (OR 7.67, P = 0.03) aortic valve replacements. CONCLUSIONS: Serum ß2-microglobulin had the potential to predict acute kidney injury complicating transcatheter valve replacement and to diagnose it as early as 24 h after both the transcatheter and the surgical procedures. Furthermore, the serum level of ß2-microglobulin was indicative of the progression of chronic kidney disease.

Significance of the age of transfused blood for prognosis after transcatheter aortic valve implantation.

INTRODUCTION    Blood transfusion after transcatheter aortic valve implantation (TAVI) is frequently required owing to the high vulnerability of this patient group and procedure-related bleeding. OBJECTIVES    We assessed the impact of postprocedural blood transfusion and the age of transfused red blood cell (RBC) units on prognosis after TAVI. PATIENTS AND METHODS    This was a single-center, observational analysis conducted between the years 2009 and 2014. The adopted endpoints were early and long-term mortality after TAVI. The risk factors for mortality included in-hospital bleeding and vascular complications, the number of transfused RBC units, transfusion of at least 2 RBC units, the age of transfused RBCs, and standard deviation of the age of RBCs. RESULTS    The study included 178 patients (mean [SD] age, 80.07 [7.47] years; range, 55-91 years). The follow-up ranged between 1 month and 5.8 years (mean [SD], 20.1 [15.2] months) after discharge; 14 early deaths (7.8%) and 27 late deaths (16.5%) were noted. In-hospital bleeding and vascular complications increased the risk of early deaths (hazard ratio [HR], 2.113; 95% CI, 1.011-4.418; P = 0.046 and HR, 2.265; 95% CI, 1.270-4.039; P = 0.005). Transfusion of younger RBCs (HR, 1.044; 95% CI, 1.004-1.085; P = 0.028) and a greater discrepancy in the age of transfused RBCs (HR, 1.153; 95% CI, 1.042-1.275; P = 0.006) were positively correlated with the risk of late deaths only in a univariate analysis. A higher number of transfused RBC units was the only independent predictor of long-term mortality (HR, 1.149; 95% CI, 1.024-1.291; P = 0.018). CONCLUSIONS    The higher number of RBC units transfused early after TAVI worsens long-term prognosis. Shorter-storage RBCs and a greater discrepancy in RBC age in multitransfused elderly patients after TAVI might have a deleterious effect on life expectancy.

Role of ß2-microglobulin in postoperative cognitive decline.

AIM: ß2-microglobulin (ß2M) was proved to affect hippocampal functions in mice. MATERIALS & METHODS: Seventy-one patients undergoing aortic valve replacement were analyzed in prospective observational study. Kidney biomarkers and Mini Mental State Examinations (MMSEs) were performed before procedure, at discharge and after 6 months. RESULTS: Patients with ß2M increase over the median change (>0.42 mg/l) experienced a significant in-hospital drop in MMSE (p = 0.005). Patients with ß2M increase over the median change also failed to improve a delayed-word-recall domain of the test (p = 0.826) while patients with a lower increase improved results in the domain (p = 0.004). After 6 months, MMSE improvement was associated with a significant decrease in ß2M (p = 0.042). CONCLUSION: These are the first in man data demonstrating relation between changes in cognition and ß2M. The phenomenon was reversible which indicates its therapeutic potential.