Advances in the Management of Heart Failure with Reduced Ejection Fraction; The Role of SGLT2is, ARNI, Myotropes, Vericiguat, and Anti-inflammatory Agents: A Mini-review.

Heart failure with reduced ejection fraction (HFrEF) has been associated with poor prognosis, reduced quality of life, and increased healthcare expenditure. Despite tremendous advances in HFrEF management, reduced survival and a high rate of hospitalization remain unsolved issues. Furthermore, HFrEF morbidity and economic burden are estimated to increase in the following years; hence, new therapies are constantly emerging. In the last few years, a series of landmark clinical trials have expanded our therapeutic armamentarium with a ground-breaking change in HFrEF-related outcomes. Sodium-glucose co-transporter 2 inhibitors (mainly dapagliflozin and empagliflozin) have already revolutionized the management of HFrEF patients via a significant reduction in cardiovascular mortality and heart failure hospitalizations. Furthermore, vericiguat and omecamtiv mecarbil have emerged as promising and novel disease-modifying therapies. The former restores the impaired cyclic guanosine monophosphate pathway, and the latter stimulates cardiac myosin without marked arrhythmogenesis. Both vericiguat and omecamtiv mecarbil have been shown to reduce heart failure admissions. Sacubitril/valsartan is an established and effective therapy in HFrEF patients and should be considered as a replacement for angiotensin-converting enzyme inhibitors (ACEi) or angiotensin II receptor blockers (ARBs). Lastly, inflammasome activity is implicated in HFrEF pathophysiology, and the role of anti-inflammatory agents in HFrEF trajectories is readily scrutinized, yet available therapies are ineffective. This mini-review summarizes the major and most recent studies in this field, thus covering the current advances in HFrEF therapeutics.

The Greek study in the effects of colchicine in COvid-19 complications prevention (GRECCO-19 study): Rationale and study design.

OBJECTIVE: Colchicine has been utilized safely in a variety of cardiovascular clinical conditions. Among its potential mechanisms of action is the non-selective inhibition of NLRP3 inflammasome which is thought to be a major pathophysiologic component in the clinical course of patients with COVID-19. GRECCO-19 will be a prospective, randomized, open-labeled, controlled study to assess the effects of colchicine in COVID-19 complications prevention. METHODS: Patients with laboratory confirmed SARS-CoV-2 infection (under RT PCR) and clinical picture that involves temperature >37.5 oC and at least two out of the: i. sustained coughing, ii. sustained throat pain, iii. Anosmia and/or ageusia, iv. fatigue/tiredness, v. PaO2<95 mmHg will be included. Patients will be randomised (1:1) in colchicine or control group. RESULTS: Trial results will be disseminated through peer-reviewed publications and conference presentations. CONCLUSION: GRECCO-19 trial aims to identify whether colchicine may positively intervene in the clinical course of COVID-19. (ClinicalTrials.gov Identifier: NCT04326790).

MicroRNAs and the heart: small things do matter.

MicroRNAs are small RNA molecules and constitute a relatively novel class of gene expression regulators, found in the great majority of eukaryotic cells. Their role in human physiology and pathology is actively being researched with new exciting discoveries continuously coming to the forefront. MicroRNAs play a crucial role in the biogenesis and function of the cardiovascular system and act as important regulators of various metabolic and signaling pathways in cardiovascular disease. In this review there will be a summary on current knowledge about the expression, regulation and function of microRNAs in the most common diseases of the cardiovascular system as well as a presentation of and discussion about their promising future role as new biomarkers and therapeutic targets.

Association of post-cardioversion transcardiac concentration gradient of soluble tumor necrosis factor-related apoptosis-inducing ligand (sTRAIL) and inflammatory biomarkers to atrial fibrillation recurrence.

OBJECTIVES: Soluble tumor necrosis factor-related apoptosis-inducing ligand (sTRAIL) has been shown to have both pro- and anti-apoptotic activities and is associated to better prognosis in heart failure. The aim of this study was to determine the transcardiac concentration gradient of sTRAIL and inflammatory biomarkers after AF cardioversion and assess their relation to AF recurrence. DESIGN AND METHODS: We measured transcardiac gradients (coronary sinus concentration minus aortic root concentration) of sTRAIL, C-reactive protein (hsCRP) and interleukin-6 (IL-6) in patients with non-valvular AF after electrical cardioversion. Six-month AF recurrence was the study endpoint. RESULTS: There were no differences in sTRAIL and hsCRP concentrations in peripheral venous blood between patients with and without AF recurrence (p=0.066 and 0.149, respectively), while IL-6 was higher in patients with recurrence (p=0.032). Only sTRAIL showed a significant transcardiac gradient [3 pg/mL (IQR 1-4 pg/mL); p=0.01]. sTRAIL gradient was 4 pg/mL (IQR 3-5 pg/mL) in patients without recurrence versus -1 pg/mL (IQR -2-1 pg/mL) in those with recurrence (p<0.001). IL-6 (p=0.281) and hsCRP (p=0.979) aortic concentrations were not significantly different from coronary sinus concentrations. In multivariate analysis, sTRAIL transcardiac gradient (beta -0.81, p=0.004) remained a negative predictor of AF recurrence. CONCLUSION: This study demonstrates the existence of a significant transcardiac sTRAIL concentration gradient in patients with non-valvular AF, inversely associated to AF recurrence. These results suggest production of sTRAIL by the heart and a protective role against substrate-altering processes in AF-prone atria. This could have implications for TRAIL-targeting therapies currently under development.

Colchicine for prevention of early atrial fibrillation recurrence after pulmonary vein isolation: a randomized controlled study.

OBJECTIVES: The purpose of the present study was to test the potential of colchicine, an agent with potent anti-inflammatory action, to reduce atrial fibrillation (AF) recurrence after pulmonary vein isolation in patients with paroxysmal AF. BACKGROUND: Proinflammatory processes induced by AF ablation therapy have been implicated in postablation arrhythmia recurrence. METHODS: Patients with paroxysmal AF who received radiofrequency ablation treatment were randomized to a 3-month course of colchicine 0.5 mg twice daily or placebo. C-reactive protein (CRP) and interleukin (IL)-6 levels were measured on day 1 and on day 4 of treatment. RESULTS: In the 3-month follow-up, recurrence of AF was observed in 27 (33.5%) of 80 patients of the placebo group versus 13 (16%) of 81 patients who received colchicine (odds ratio: 0.38, 95% confidence interval: 0.18 to 0.80). Gastrointestinal side-effects were the most common symptom among patients receiving active treatment. Diarrhea was reported in 7 patients in the colchicine group (8.6%) versus 1 in the placebo group (1.3%, p = 0.03). Colchicine led to higher reductions in CRP and IL-6 levels: the median difference of CRP and IL-6 levels between days 4 and 1 was -0.46 mg/l (interquartile range: -0.78 to 0.08 mg/l) and -0.10 mg/l (-0.30 to 0.10 pg/ml), respectively, in the placebo group versus -1.18 mg/l (-2.35 to -0.46 mg/l) and -0.50 pg/ml (-1.15 to -0.10 pg/ml) in the colchicine group (p < 0.01 for both comparisons). CONCLUSIONS: Colchicine is an effective and safe treatment for prevention of early AF recurrences after pulmonary vein isolation in the absence of antiarrhythmic drug treatment. This effect seems to be associated strongly with a significant decrease in inflammatory mediators, including IL-6 and CRP.

Feasibility of peripheral venous access for temporary right ventricular pacing.

INTRODUCTION: In this brief report, we present our experience from placing temporary pacing electrodes through peripheral venous access sites, at bedside, in a series of patients needing temporary pacing. METHODS: Consecutive patients requiring temporary pacing were selected. The median cubital or the basilic vein of the left upper extremity were used for catheterization at the bedside in all cases. RESULTS: 25 patients (17 men, age 64.6 ± 11.8) were included. The procedure was successful in 21 cases (84%), 18 of which were completed without the need for fluoroscopic guidance. The pacing leads remained for 4.2 ± 2.2 days. As expected, no serious complications related to venous puncture were observed. Although patients were allowed to be mobilized within the ward and engage in limited movements of the catheterized arm, in only one case was the lead displaced, requiring repositioning. CONCLUSIONS: We provide observational evidence that the use of peripheral venous access for temporary pacing lead insertion (with no fluoroscopic guidance, as default strategy) is a safe and feasible choice that might be considered as an alternative to central vein catheterization.

Association of soluble tumour necrosis factor-related apoptosis-inducing ligand levels with coronary plaque burden and composition.

BACKGROUND: Evidence shows that the soluble tumour necrosis factor-related apoptosis-inducing ligand (sTRAIL) may play a protective role against atherosclerosis. This study sought to investigate the potential association of sTRAIL levels with intravascular ultrasound (IVUS) and virtual histology characteristics of coronary plaques. METHODS: Patients with stable angina or positive for ischaemia non-invasive test were submitted to left cardiac catheterisation. Coronary blood samples were collected and sTRAIL was measured. Coronary arteries with at least one 50% or greater stenosis were studied with IVUS. RESULTS: 56 coronary arteries were studied with significant coronary artery disease. Plaque volume per unit of arterial length was 63 ± 5 mm(3)/cm in arteries at the lower quartile of sTRAIL concentration versus 30 ± 4 mm(3)/cm at the upper quartile (p<0.001; 95% CI of the difference 19.7 to 46.3 mm(3)/cm). The necrotic core and fibrofatty content of atheromatous plaques were inversely associated with sTRAIL (p<0.001). Thin-cap fibroatheromas (TCFA) were discovered in 16 of the 56 arterial segments. The mean sTRAIL concentration in these segments was 56.8 ± 7.5 pg/ml versus 99.9 ± 5.7 pg/ml in those without TCFA (p<0.001; 95% CI of the difference 22.7 to 63.5 pg/ml). The association of sTRAIL with the presence of TCFA remained significant in the logistic multivariate analysis (p=0.009). CONCLUSION: According to the findings of the present study, in addition to coronary artery disease burden, the sTRAIL concentration is also related to the composition of atheromatous plaques. A significant association is demonstrated between low sTRAIL levels and the presence of TCFA, the IVUS-virtual histology prototype of the vulnerable plaque.

Transradial access as first choice for primary percutaneous coronary interventions: experience from a tertiary hospital in Athens.

INTRODUCTION: The transfemoral approach (TFA) has been the mainstay for arterial access during percutaneous coronary intervention (PCI) in the setting of acute ST-segment elevation myocardial infarction (STEMI). However, the transradial approach (TRA) has been shown to be an equally effective and possibly safer way of performing primary PCI (pPCI). METHODS: The study population included 98 serially recruited patients who underwent pPCI in our institution. All patients were clinically followed during their hospital stay (6.4 ± 3.1 days). RESULTS: In the 98 patients included in the study, 65 procedures (66.3%) were completed via TRA, whereas the remaining 33 procedures (33.7%) used TFA. Door-to-balloon time was similar (57 ± 19 min vs. 54 ± 15 min, p=ns). Patients in the TRA group were mobilized sooner (28 ± 9 hours vs. 36 ± 13 hours, p<0.05). Hospital stay was significantly shorter in the TRA group (6.0 ± 3.2 days vs. 7.1 ± 2.8 days, p<0.05). TRA and TFA did not differ significantly as to the incidence of death, non-fatal myocardial infarction or subacute stent thrombosis, but major access-related vascular complications were significantly more frequent in the TFA group (2% vs. 15%, p<0.01). Cerebrovascular events did not differ between TRA and TFA. CONCLUSIONS: Compared to TFA, TRA seems to be associated with a lower incidence of bleeding complications, as well as earlier mobilization and discharge from hospital. It is conceivable that TRA could become the first choice in the treatment of STEMI patients in the near future, while TFA is kept as an alternative.

Estimation of atrial fibrillation recency of onset and safety of cardioversion using NTproBNP levels in patients with unknown time of onset.

OBJECTIVE: As shown previously in patients with new-onset atrial fibrillation (AF) without symptoms or signs of heart failure, N-terminal pro-brain natriuretic peptide (NTproBNP) increases rapidly, reaching a maximum within 24-36 h, and then decreases even if AF persists. A study was undertaken to use NTproBNP measurements in patients with AF of unknown time of onset to identify patients with presumed recent onset of the arrhythmia. DESIGN: Two-group open cross-sectional study. SETTING: Hospitalised patients in cardiology departments of four hospitals. PATIENTS: Patients presenting with AF of unknown onset and no signs or symptoms of heart failure were separated into two groups: group A with NTproBNP above the cut-off level and group B with a low NTproBNP level. INTERVENTIONS: No therapeutic intervention. All patients underwent transoesophageal echocardiography (TEE). MAIN OUTCOME MEASURES: Presence of left atrial thrombus on TEE. RESULTS: In group A (N=43) only two patients (4.7%) were found to have an atrial thrombus on TEE (negative predictive value of raised NTproBNP levels 95.3%) compared with 13 of 43 patients in group B (30.2%; p=0.002). Patients with a higher CHA(2)DS(2)VASc score (p=0.002) and a larger left atrium (p<0.001) were more likely to have an atrial thrombus. In the multivariate analysis, NTproBNP below the cut-off level was the most powerful predictor of the presence of thrombus (OR 25.0; p=0.016). CONCLUSION: The reported strong correlation between raised NTproBNP levels and the absence of atrial thrombi on TEE suggests that the short-term increase in NTproBNP levels after AF onset might be used to assess the age of the arrhythmia and thus the safety of cardioversion in patients with AF of unknown onset and no heart failure.

Radial artery flow-mediated dilation predicts arterial spasm during transradial coronary interventions.

BACKGROUND: Transradial coronary catheterization has emerged over the last years as a favorable catheterization practice, based on evidence that it is associated with less vascular complications and shorter hospital stays. However, access site crossover appears to be more frequent when the initial route is the transradial one, one of the main reasons being arterial spasm. We hypothesized that radial flow-mediated dilation (FMD) measurements could be used as a preprocedural method to assess the likelihood of arterial spasm. METHODS: The study population consisted of patients scheduled for transradial diagnostic catheterization in whom ad hoc percutaneous coronary intervention (PCI) was performed. FMD was measured 1-2 days before PCI. The primary endpoint of the study was operator-defined (operators were blinded as to the FMD results) radial artery spasm. RESULTS: A total of 172 patients (110 male, age 65.3 ± 9) were included. Radial artery spasm was recorded in 13 patients (7.6%). FMD showed a very significant univariate association with the occurrence of spasm (P < 0.001) and was the most important predictor of spasm in the multivariate logistic regression analysis (beta -3.15; P < 0.001), followed by baseline radial artery diameter (P = 0.04), the number of catheters used (P = 0.049) and the administered volume of contrast medium (P = 0.017). CONCLUSION: Preprocedural FMD is a significant predictor of arterial spasm before elective transradial PCI. It is a low cost, safe, and feasible noninvasive modality, whose results might be taken into account when deciding on the vascular access route for an elective procedure, the size of sheaths or catheters to be used or the intensity of antispasm medication.

Differential effect of biventricular and right ventricular DDD pacing on coronary flow reserve in patients with ischemic cardiomyopathy.

UNLABELLED: CRT and Coronary Flow Reserve. BACKGROUND: Cardiac resynchronization therapy (CRT) has become a mainstay in heart failure management. There are also indications that upgrading of existing pacemakers to CRT systems may be of benefit. The aim of this study was to assess the effect of biventricular (BiV), compared with right ventricular (RV), pacing, on coronary flow reserve (CFR), in patients with ischemic cardiomyopathy. METHODS AND RESULTS: From our database of heart failure patients implanted with BiV pacemakers, 20 patients (10 responders and 10 non-responders to CRT) were randomly selected. Left anterior descending artery coronary flow reserve was measured invasively, under BiV and RV pacing, using intracoronary adenosine to induce hyperemia. In all the 20 patients, there was a significant difference in the pairwise comparison between CFR recorded during BiV and RV pacing (mean difference 0.15, 95% confidence interval 0.07-0.23, P = 0.001). When comparing responders to non-responders, there was a significant difference as to the effect of BiV, compared with RV, pacing on CFR: mean difference (BiV minus RV CFR) was 0.26 ± 0.06 (95% confidence interval 0.13-0.39; P = 0.002), while in non-responders the difference was 0.04 ± 0.03 (95% confidence interval -0.02 to 0.10; P = 0.168). CONCLUSION: BiV pacing is overall associated to higher CFR, compared with RV DDD pacing. This difference is almost exclusively attributable to the beneficial effect of CRT on coronary flow reserve in CRT-responders. This effect may contribute to the beneficial action of resynchronization in the failing heart and can be viewed in the context of reports of the usefulness of upgrading RV pacemakers to CRT systems.