Association between Ranolazine, Ischemic Preconditioning, and Cardioprotection in Patients Undergoing Scheduled Percutaneous Coronary Intervention.

Background and Objectives: Remote ischemic preconditioning (RIPC) has demonstrated efficacy in protecting against myocardial ischemia-reperfusion injury when applied before percutaneous coronary revascularization. Ranolazine, an anti-ischemic drug, has been utilized to minimize ischemic events in chronic angina patients. However, there is a lack of trials exploring the combined effects of ranolazine pretreatment and RIPC in patients undergoing percutaneous coronary interventions (PCIs). Materials and Methods: The present study is a prospective study which enrolled 150 patients scheduled for nonemergent percutaneous coronary revascularization. Three groups were formed: a control group undergoing only PCIs, an RIPC group with RIPC applied to either upper limb before the PCI (preconditioning group), and a group with RIPC before the PCI along with prior ranolazine treatment for stable angina (ranolazine group). Statistical analyses, including ANOVAs and Kruskal-Wallis tests, were conducted, with the Bonferroni correction for type I errors. A repeated-measures ANOVA assessed the changes in serum enzyme levels (SGOT, LDH, CRP, CPK, CK-MB, troponin I) over the follow-up. Statistical significance was set at p < 0.05. Results: The ranolazine group showed (A) significantly lower troponin I level increases compared to the control group for up to 24 h, (B) significantly lower CPK levels after 4, 10, and 24 h compared to the preconditioning group (p = 0.020, p = 0.020, and p = 0.019, respectively) and significantly lower CPK levels compared to the control group after 10 h (p = 0.050), and (C) significantly lower CK-MB levels after 10 h compared to the control group (p = 0.050). Conclusions: This study suggests that combining RIPC before scheduled coronary procedures with ranolazine pretreatment may be linked to reduced ischemia induction, as evidenced by lower myocardial enzyme levels.

One-Year Outcomes in Anticoagulated Atrial Fibrillation Patients Undergoing Percutaneous Coronary Intervention: Insights From the Greek Antiplatelet Atrial Fibrillation Registry.

ABSTRACT: GReek-AntiPlatElet Atrial Fibrillation registry is a multicenter, observational, noninterventional study of atrial fibrillation patients undergoing percutaneous coronary intervention. Primary endpoint included clinically significant bleeding rate at 12 months between different antithrombotic regimens prescribed at discharge; secondary endpoints included major adverse cardiovascular events and net adverse clinical events. A total of 647 patients were analyzed. Most (92.9%) were discharged on novel oral anticoagulants with only 7.1% receiving the vitamin K antagonist. A little over half of patients (50.4%) received triple antithrombotic therapy (TAT)-mostly (62.9%) for ≤1 month-whereas the rest (49.6%) received dual antithrombotic therapy (DAT). Clinically significant bleeding risk was similar between TAT and DAT [Hazard ratio (HR) = 1.08; 95% confidence interval (CI), 0.66-1.78], although among TAT-receiving patients, the risk was lower in those receiving TAT for ≤1 month (HR = 0.50; 95% CI, 0.25-0.99). Anticoagulant choice (novel oral anticoagulant vs. vitamin K antagonist) did not significantly affect bleeding rates ( P = 0.258). Age, heart failure, leukemia/myelodysplasia, and acute coronary syndrome were associated with increased bleeding rates. Risk of major adverse cardiovascular events and net adverse clinical events was similar between ΤAT and DAT (HR = 1.73; 95% CI, 0.95-3.18, P = 0.075 and HR = 1.39; 95% CI, 0.93-2.08, P = 0.106, respectively). In conclusion, clinically significant bleeding and ischemic rates were similar between DAT and TAT, although TAT >1 month was associated with higher bleeding risk.

Platelet function testing in atrial fibrillation patients undergoing percutaneous coronary intervention.

Platelet function testing (PFT) could be a useful clinical tool to guide individualized antithrombotic treatment in patients with atrial fibrillation (AF) undergoing percutaneous coronary intervention (PCI). We aimed to investigate platelet reactivity (PR) in the context of a contemporary registry. "Real-world" data were retrieved from a nationwide, multicenter, observational study of AF patients on oral anticoagulants (OAC) undergoing PCI. Patients treated with a P2Y12 inhibitor, namely clopidogrel or ticagrelor, as part of double or triple antithrombotic therapy, were submitted to PFT before discharge and were followed up for 12 months. Out of 101 patients included in the study, 66 were submitted to PFT while on clopidogrel and 35 while on ticagrelor; PR was 162.9 ± 68 PRU and 46.02 ± 46 PRU, respectively (P < 0.001). High on-treatment PR (HTPR) was observed in 15 patients under clopidogrel (22.7%); 7 of them escalated to ticagrelor. Low on-treatment PR (LTPR) was found in 9 clopidogrel and 28 ticagrelor-treated patients (13.6% vs. 80%, P < 0.001), of whom only 1 de-escalated to clopidogrel. PR did not differ by OAC regimen. PFT results had no impact on aspirin prescription at discharge, while failed to predict significant bleeding events at follow up. Ticagrelor administration led to lower PR and lower incidence of HTPR in comparison with clopidogrel. Physicians' behavior in response to knowledge of a patient's PR was variable. Further studies are required to elucidate the role of PFT as a tool to guide individualized antithrombotic treatment in this clinical scenario.

Angiotensin receptor-neprilysin inhibition in patients with acute decompensated heart failure: an expert consensus position paper.

The short-term mortality and rehospitalization rates after admission for acute heart failure (AHF) remain high, despite the high level of adherence to contemporary practice guidelines. Observational data from non-randomized studies in AHF strongly support the in-hospital administration of oral evidence-based modifying chronic heart failure (HF) medications (i.e., b-blockers, ACE inhibitors, mineralocorticoid receptor antagonists) to reduce morbidity and mortality. Interestingly, a well-designed prospective randomized multicenter study (PIONEER-HF) showed an improved clinical outcome and stress/injury biomarker profile after in-hospital administration of sacubitril/valsartan (sac/val) as compared to enalapril, in hemodynamically stable patients with AHF. However, sac/val implementation during hospitalization remains suboptimal due to the lack of an integrated individualized plan or well-defined appropriateness criteria for transition to oral therapies, an absence of specific guidelines regarding dose selection and the up-titration process, and uncertainty regarding patient eligibility.In the present expert consensus position paper, clinical practical recommendations are proposed, together with an action plan algorithm, to encourage and facilitate sac/val administration during hospitalization after an AHF episode with the aim of improving efficiencies of care and resource utilization.

A novel machine learning-based approach for the computational functional assessment of pharmacogenomic variants.

BACKGROUND: The field of pharmacogenomics focuses on the way a person's genome affects his or her response to a certain dose of a specified medication. The main aim is to utilize this information to guide and personalize the treatment in a way that maximizes the clinical benefits and minimizes the risks for the patients, thus fulfilling the promises of personalized medicine. Technological advances in genome sequencing, combined with the development of improved computational methods for the efficient analysis of the huge amount of generated data, have allowed the fast and inexpensive sequencing of a patient's genome, hence rendering its incorporation into clinical routine practice a realistic possibility. METHODS: This study exploited thoroughly characterized in functional level SNVs within genes involved in drug metabolism and transport, to train a classifier that would categorize novel variants according to their expected effect on protein functionality. This categorization is based on the available in silico prediction and/or conservation scores, which are selected with the use of recursive feature elimination process. Toward this end, information regarding 190 pharmacovariants was leveraged, alongside with 4 machine learning algorithms, namely AdaBoost, XGBoost, multinomial logistic regression, and random forest, of which the performance was assessed through 5-fold cross validation. RESULTS: All models achieved similar performance toward making informed conclusions, with RF model achieving the highest accuracy (85%, 95% CI: 0.79, 0.90), as well as improved overall performance (precision 85%, sensitivity 84%, specificity 94%) and being used for subsequent analyses. When applied on real world WGS data, the selected RF model identified 2 missense variants, expected to lead to decreased function proteins and 1 to increased. As expected, a greater number of variants were highlighted when the approach was used on NGS data derived from targeted resequencing of coding regions. Specifically, 71 variants (out of 156 with sufficient annotation information) were classified as to "Decreased function," 41 variants as "No" function proteins, and 1 variant in "Increased function." CONCLUSION: Overall, the proposed RF-based classification model holds promise to lead to an extremely useful variant prioritization and act as a scoring tool with interesting clinical applications in the fields of pharmacogenomics and personalized medicine.

Right drug, wrong dosage: insights from the PAVE-AF antithrombotic study in older patients with atrial fibrillation.

Optimal antithrombotic treatment of older patients is usually impeded by several prevailing misconceptions. The aim of our study was to assess the type, dosage and predictors of antithrombotic therapy in older patients with non-valvular atrial fibrillation (NVAF). PAVE-AF was a prospective, cross-sectional study, including NVAF patients ≥ 80 years from 30 participating centers. Demographic data, comorbidities and treatment patterns were documented in a single visit. Patients treated with non-vitamin K oral anticoagulants (NOACs) were further classified into three dosing categories (recommended, underdosing and overdosing). Among 1018 patients (85.4±4.0 years), 88.4% received anticoagulants (AC), 8% antiplatelets (AP) and 3.6% no treatment. The primary reason for AP administration was physician concern of bleeding followed by patient denial. Patients ≥90 years had two times greater probability to receive AP therapy compared to patients < 90 years. Among patients treated with AC, one third received vitamin K antagonists, while two thirds received NOACs [34.6% apixaban, 9.5% dabigatran and 22.6% rivaroxaban]. Independent predictors of AC prescription over AP or no treatment were low HAS-BLED score, hypertension, labile INR, permanent AF, absence of uncontrolled hypertension, prior stroke/systemic embolism, age and male gender. In total, 37% of NOAC recipients received inappropriate dosage, while the number of patients receiving recommended dosing differed significantly among NOAC subgroups (p < 0.001). In our study, a minority of older NVAF patients received AP or no therapy for stroke prevention. Among patients treated with anticoagulants, two thirds were on NOAC treatment, though with a considerable proportion of inappropriate dosing.

Red blood cell distribution width as a prognostic marker in patients with heart failure and diabetes mellitus.

BACKGROUND: Red blood cell distribution width (RDW) is an established prognostic marker in acute and chronic heart failure (HF). Recent studies have pointed out a link among RDW, diabetes mellitus (DM) and inflammation. We sought to investigate the prognostic value and longitudinal pattern of RDW in patients with concomitant HF and DM, which remains unknown. METHODS: A total of 218 patients (71 diabetics) who presented with acute HF had RDW measured at admission, discharge and 4, 8 and 12 months post-discharge. The study endpoint was all-cause mortality or rehospitalization for HF during 1-year follow-up. RESULTS: The study endpoint was met in 33 patients (46.5%) with DM and in 54 patients (36.7%) without DM. RDW at admission was associated with higher event rate both in HF patients with and without DM (adjusted HR: 1.349, p = 0.002, 95% CI 1.120-1.624 and adjusted HR: 1.142, p = 0.033, 95% CI 1.011-1.291 respectively). In addition, a significant interaction was found between diabetes and RDW longitudinal changes (ßinteraction = -0.002; SE = 0.001; p = 0.042). CONCLUSIONS: Despite the similar prognostic significance of RDW in diabetic and non-diabetic HF patients regarding the study endpoint, longitudinal changes were found to be significantly different between these two groups of HF patients. This might be due to the higher inflammatory burden that diabetic HF patients carry and may provide new insights to the pathophysiological mechanism of RDW increase in HF, which remains unknown.

Factors Affecting Platelet Reactivity 2 Hours After P2Y12 Receptor Antagonist Loading in Primary Percutaneous Coronary Intervention for ST-Elevation Myocardial Infarction - Impact of Pain-to-Loading Time.

BACKGROUND: Delay in the onset of antiplatelet action occurs in patients with ST-elevation myocardial infarction (STEMI) and is likely due to disturbed absorption. We hypothesized that patients presenting relatively late after the onset of symptoms would have faster antiplatelet action. METHODS AND RESULTS: We analyzed patient-level data from 5 studies of 207 P2Y12 receptor antagonist-naïve patients with STEMI undergoing primary percutaneous coronary intervention (PCI). All patients had available platelet reactivity (PR) assessment with the VerifyNow assay (in P2Y12 reaction units; PRU) prior to and 2 h after loading. High PR (HPR) was defined as ≥ 208 PRU. Pain-to-antiplatelet loading time independently predicted PR at 2 h after loading: every 1-h increase in pain-to-antiplatelet loading time produced a 7% decrease in PR (P=0.001). Pretreatment PR, body mass index, morphine and novel P2Y12 receptor antagonist also affected PR 2 h after loading. Novel P2Y12 receptor antagonist use and per hour increase in pain-to-antiplatelet loading time were independently associated with lower probability for HPR with an OR (95% CI) of 0.145 (0.095-0.220) and 0.776 (0.689-0.873), P<0.001 for both (C-statistic, 0.752; 95% CI: 0.685-0.819). CONCLUSIONS: In STEMI patients undergoing primary PCI, pain-to-antiplatelet loading interval is a newly described factor affecting PR shortly after P2Y12 receptor antagonist loading, according to patient-level data pooled analysis.

Ticagrelor vs clopidogrel followed by ticagrelor re-loading in patients with ST-segment elevation myocardial infarction undergoing primary percutaneous coronary intervention: A randomized, pharmacodynamic comparison.

Among patients allocated to ticagrelor in the primary percutaneous coronary intervention (PCI) cohort of Platelet Inhibition and Patient Outcomes (PLATO) trial, 40.7% had received pre-randomization 600 mg of clopidogrel. This scenario is frequently employed in real-world practice. In a prospective, three-center, single-blind, parallel design study, 74 P2Y12 inhibitor-naive patients undergoing primary PCI were randomized (Hour 0) to ticagrelor 180 mg loading dose (LD) vs clopidogrel 600 mg LD followed after 2 h by ticagrelor 180 mg re-LD. Platelet reactivity (VerifyNow, in PRU) was assessed at Hour 0, 2, 4, 6, and 24. The primary comparison was non-inferiority of ticagrelor to clopidogrel followed by ticagrelor re-LD regarding platelet reactivity at 24 h using a prespecified margin of <35 PRU for the upper bound of the one-sided 97.5% confidence interval (CI). Ticagrelor was proven non-inferior to clopidogrel followed by ticagrelor re-LD with a difference between arms of 13.5 PRU (28.8 upper 97.5% CI), p = 0.001. At Hour 2, platelet reactivity was lower in ticagrelor only vs clopidogrel followed by ticagrelor re-LD groups with least square estimate mean difference (95% CI) -105.7 (-140.6 to -70.8), p < 0.001, without significant difference thereafter. In conclusion, in patients undergoing primary PCI, a strategy of ticagrelor LD only was proven non-inferior to clopidogrel LD followed by ticagrelor re-LD, in terms of antiplatelet efficacy at 24 h post-randomization and provided an earlier onset of platelet inhibition.

Ticagrelor versus high dose clopidogrel in ST-segment elevation myocardial infarction patients with high platelet reactivity post fibrinolysis.

Limited data are available on high platelet reactivity (HPR) rate early post fibrinolysis, while no effective way to overcome it has been proposed. In this context, we aimed to compare ticagrelor versus high dose clopidogrel in patients with ST-segment elevation myocardial infarction (STEMI) who exhibit HPR post fibrinolysis. In a prospective, randomized, parallel design, 3-center study, 56 STEMI patients, out of 83 (67.5 %) screened, who presented with HPR (PRU ≥ 208 by VerifyNow) 3-48 h post fibrinolysis and prior to coronary angiography were allocated to ticagrelor 180 mg loading dose (LD)/90 mg bid maintenance dose (MD) or clopidogrel 600 mg LD/150 mg MD. Platelet reactivity was assessed at randomization (Hour 0), at Hour 2, Hour 24 and pre-discharge. The primary endpoint of platelet reactivity (in PRU) at Hour 2 was significantly lower for ticagrelor compared to clopidogrel with a least square mean difference (95 % confidence interval) of -141.7 (-173.4 to -109.9), p < 0.001. HPR rates at Hour 2 and 24 were significantly lower for ticagrelor versus clopidogrel (14.3 vs. 82.1 %, p < 0.001 and 0 vs. 25.0 %, p = 0.01 respectively), though not significantly different pre-discharge. In-hospital Bleeding Academic Research Consortium type ≥2 bleeding occurred in 1 and 2 clopidogrel and ticagrelor-treated patients, respectively. In STEMI patients, post fibrinolysis HPR is common. Ticagrelor treats HPR more effectively compared to high dose clopidogrel therapy. Although antiplatelet regimens tested in this study were well tolerated, this finding should be considered only exploratory.

Five-year morbidity and mortality of patients with ischemia with non-obstructive coronary artery disease and myocardial single-photon emission computed tomography perfusion defects.

INTRODUCTION: Patients with angina and a positive single-photon emission computed tomography (SPECT) scan for reversible ischemia, with no or non-obstructive coronary artery disease (CAD) on invasive coronary angiography (ICA), represent a frequent clinical problem and predicting prognosis is challenging. METHODS: This was a retrospective single-center study on patients who underwent elective ICA with angina and a positive SPECT with no or non-obstructive CAD over a seven-year period. Cardiovascular morbidity, mortality, and major adverse cardiac events were assessed during a follow-up of at least three years after ICA, with the aid of a telephone questionnaire. RESULTS: Data on all patients who underwent ICA in our hospital over a period of seven years (between January 1, 2011 and December 31, 2017) were analyzed. A total of 569 patients fulfilled the pre-specified criteria. In the telephone survey, 285 (50.1%) were successfully contacted and agreed to participate. Mean age was 67.6 (SD 8.8) years (35.4% female) and mean follow-up was 5.53 years (SD 1.85). Mortality was 1.7% (four patients, from non-cardiac causes), 1.7% underwent revascularization, 31 (10.9%) were hospitalized for cardiac reasons and 10.9% reported symptoms of heart failure (no patients with NYHA class>II). Twenty-one had arrhythmic events and only two had mild anginal symptoms. It was also noteworthy that mortality in the uncontacted group (12 out of 284, 4.2%), derived from public social security records, did not differ significantly from the contacted group. CONCLUSIONS: Patients with angina, a positive SPECT for reversible ischemia and no or non-obstructive CAD on ICA have excellent long-term cardiovascular prognosis for at least five years.

Association between Dapagliflozin, Cardiac Biomarkers and Cardiac Remodeling in Patients with Diabetes Mellitus and Heart Failure.

Sodium-glucose cotransporter-2 inhibitors (SGLT2is) are a relatively new class of antidiabetic drugs that have shown favorable effects in heart failure (HF) patients, irrespective of the left ventricular ejection fraction (LVEF). Recent studies have demonstrated the beneficial effects of empagliflozin on cardiac function and structure; however, less is known about dapagliflozin. The purpose of the current work was to investigate the association between the use of dapagliflozin and cardiac biomarkers as well as the cardiac structure in a cohort of patients with HF and diabetes mellitus (DM). The present work was an observational study that included 118 patients (dapagliflozin group n = 60; control group n = 58) with HF and DM. The inclusion criteria included: age > 18 years, a history of DM and HF, regardless of LVEF, and hospitalization for HF exacerbation within the previous 6 months. The exclusion criteria were previous treatment with SGLT2i or glucagon-like peptide-1 receptor agonists, a GFR< 30 and life expectancy < 1 year. The evaluation of patients (at baseline, 6 and 12 months) included a clinical assessment, laboratory blood tests and echocardiography. The Mann-Whitney test was used for the comparison of continuous variables between the two groups, while Friedman's analysis of variance for repeated measures was used for the comparison of continuous variables. Troponin (p < 0.001) and brain natriuretic peptide (BNP) (p < 0.001) decreased significantly throughout the follow-up period in the dapagliflozin group, but not in the control group (p > 0.05 for both). The LV end-diastolic volume index (p < 0.001 for both groups) and LV end-systolic volume index (p < 0.001 for both groups) decreased significantly in the dapagliflozin and the control group, respectively. The LVEF increased significantly (p < 0.001) only in the dapagliflozin group, whereas the global longitudinal strain (GLS) improved in the dapagliflozin group (p < 0.001) and was impaired in the control group (p = 0.021). The left atrial volume index decreased in the dapagliflozin group (p < 0.001) but remained unchanged in the control group (p = 0.114). Lastly, the left ventricular mass index increased significantly both in the dapagliflozin (p = 0.003) and control group (p = 0.001). Dapagliflozin, an SGLT2i, was associated with a reduction in cardiac biomarkers and with reverse cardiac remodeling in patients with HF and DM.

The burden of atrial fibrillation and heart failure in hospitalized patients: A real-world survey in a nationwide snapshot.

PURPOSE: Atrial fibrillation (AF) and heart failure (HF) are common and commonly coexisting cardiovascular diseases in hospitalized patients. We report the absolute number and interrelation between AF and HF, assess the daily burden of both diseases on the healthcare system, and describe the medical treatment in a real-world, nationwide conducted snapshot survey. METHODS: A questionnaire was equally distributed to various healthcare institutions. Data on the baseline characteristics, prior hospitalizations, and medical treatments of all hospitalized patients with AF and HF at a predefined date were collected and analyzed. RESULTS: Seventy-five cardiological departments participated in this multicenter Greek nationwide study. A total of 603 patients (mean age, 74.5 ± 11.4 years) with AF, HF, or the combination of both were nationwide admitted. AF, HF, and the combination of both were registered in 122 (20.2%), 196 (32.5%), and 285 (47.3%) patients, respectively. First-time hospital admission was recorded in 273 (45.7%) of 597 patients, whereas 324 (54.3%) of 597 patients had readmissions in the past 12 months. Of the entire population, 453 (75.1%) were on beta-blockers (BBs), and 430 (71.3%) were on loop diuretics. Furthermore, 315 patients with AF (77.4%) were on oral anticoagulation, of whom 191 (46.9%) were on a direct oral anticoagulant and 124 (30.5%) were on a vitamin K antagonist. CONCLUSION: Hospitalized patients with AF and/or HF have more than one admission within a year. Coexistence of AF and HF is more common. BBs and loop diuretics are the most commonly used drugs. More than three-quarters of the patients with AF were on oral anticoagulation.

Cardiorenal multimorbidity in hospitalized cardiology patients: The Hellenic Cardiorenal Morbidity Snapshot (HECMOS) study.

PURPOSE: Cardiovascular disease is commonly accompanied by renal dysfunction. Multimorbidity in hospitalized patients impacts unfavorably on prognosis and hospital stay. We aimed to illustrate the contemporary burden of cardiorenal morbidity across inpatient cardiology care in Greece. METHODS: The Hellenic Cardiorenal Morbidity Snapshot (HECMOS) used an electronic platform to collect demographic and clinically relevant information about all patients hospitalized on March 3, 2022, in Greece. The participating institutions covered all levels of inpatient cardiology care and most of the country's territories to collect a real-world, nation representative sample. RESULTS: A total of 923 patients (men 68.4%, median age 73 ± 14.8 years) were admitted to 55 different cardiology departments. 57.7% of the participants were aged >70 years. Hypertension was highly prevalent and present in 66% of the cases. History of chronic HF, diabetes mellitus, atrial fibrillation, and chronic kidney disease was present in 38%, 31.8%, 30%, and 26%, respectively. Furthermore, 64.1% of the sample exhibited at least one of these 4 entities. Accordingly, a combination of ≥2 of these morbid conditions was recorded in 38.7%, of ≥3 in 18.2%, whereas 4.3% of the sample combined all 4 in their medical history. The most common combination was the coexistence of heart failure-atrial fibrillation accounting for 20.6% of the sample. Nine of 10 nonelectively admitted patients were hospitalized due to acute HF (39.9%), acute coronary syndrome (33.5%), or tachyarrhythmias (13.2%). CONCLUSION: HECMOS participants carried a remarkable burden of cardio-reno-metabolic disease. HF in conjunction with atrial fibrillation was found to be the most prevalent combination among the studied cardiorenal nexus of morbidities in the whole study population.

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.

Brain natriuretic peptide: a marker of cardiac dysfunction with ventricular or dual-chamber pacing.

BACKGROUND/OBJECTIVES: The inability of trials to exhibit the superiority in survival of atrioventricular compared to ventricular pacing can be partially explained by the apical stimulation of the right ventricle, which adversely affects both short- and long-term ventricular performance. We evaluated the impact of pacing mode (DDDR vs. VVIR) on the brain natriuretic peptide (BNP) level in patients with sick-sinus syndrome (SSS). METHODS: Sixty-seven patients were treated with DDDR pacemaker implantation due to SSS. They were randomized during the first post-implant day either to DDDR or WIR pacing mode and were reevaluated after 30 days. Group A comprised 35 patients on DDDR pacing mode and group B 32 patients on WIR pacing mode. Peripheral blood samples were drawn for BNP measurement at the time of randomization and one month later. RESULTS: BNP levels increased significantly in both groups at 30 days (group A: 85.6 +/- 29.5 pg/ml to 107.2 +/- 34.6 pg/ml, group B: 82.7 +/- 27.6 pg/ml to 253.1 +/- 60.2 pg/ml). On day 30, BNP levels in group B were significantly higher than in group A (P < 0.0001). CONCLUSIONS: Pacing from the apex of the right ventricle provokes an increase in the BNP levels regardless of the pacing mode. BNP is probably a very early marker predicting the structural and/or functional heart changes after long-term pacing from the apex of the right ventricle.

Patent hemostasis of radial artery: Comparison of two methods.

BACKGROUND: Radial artery obstruction is the most common complication of coronary angiography performed via transradial access. Patent hemostasis can significantly reduce the risk of radial artery occlusion. Previous studies utilized sophisticated methods to evaluate radial artery patency. Simplified and easily applicable methods for successful patent hemostasis are currently lacking. AIM: To determine which method (pulse oximeter vs the traditional radial artery palpation) is better to achieve patent hemostasis. METHODS: This prospective, single center study included 299 consecutive patients who underwent coronary angiography or percutaneous coronary intervention between November 2017 and July 2019. Patients less than 18 years old, with a history of radial artery disease, or no palpable artery pulse were excluded from the study. Patients were randomly assigned to two groups. In the first group, radial artery flow was assessed by palpation of the artery during hemostasis (traditional method). In the second group, radial artery patency was estimated with the use of a pulse oximeter. Two different compression devices were used for hemostasis (air chamber and pressure valve). The primary study endpoint was the achievement of successful patent hemostasis. RESULTS: The two groups (pulse oximeter vs artery palpation) had no significant differences in age, sex, body mass index, risk factors, or comorbidities except for supraventricular arrhythmias. The percentage of patients with successful patent hemostasis was significantly higher in the pulse oximeter group (82.2% vs 68.1%, P = 0.005). A lower percentage of patients with spasm was recorded in the pulse oximeter group (9.9% vs 19.0%, P = 0.024). The incidence of local complications, edema, bleeding, hematoma, vagotonia, or pain did not differ between the two groups. In the multivariate analysis, the use of a pulse oximeter (OR: 2.35, 95%CI: 1.34-4.13, P = 0.003) and advanced age (OR: 1.04, 95%CI: 1.01-1.07, P = 0.006), were independently associated with an increased probability of successful patent hemostasis. The type of hemostatic device did not affect patent hemostasis (P = 0.450). CONCLUSION: Patent hemostasis with the use of pulse oximeter is a simple, efficient, and safe method that is worthy of further investigation. Larger randomized studies are required to consider its clinical implications.

"Missing" acute coronary syndrome hospitalizations during the COVID-19 era in Greece: Medical care avoidance combined with a true reduction in incidence?

BACKGROUND: Reports from countries severely hit by the COVID-19 pandemic suggest a decline in acute coronary syndrome (ACS)-related hospitalizations. The generalizability of this observation on ACS admissions and possible related causes in countries with low COVID-19 incidence are not known. HYPOTHESIS: ACS admissions were reduced in a country spared by COVID-19. METHODS: We conducted a nationwide study on the incidence rates of ACS-related admissions during a 6-week period of the COVID-19 outbreak and the corresponding control period in 2019 in Greece, a country with strict social measures, low COVID-19 incidence, and no excess in mortality. RESULTS: ACS admissions in the COVID-19 (n = 771) compared with the control (n = 1077) period were reduced overall (incidence rate ratio [IRR]: 0.72, P < .001) and for each ACS type (ST-segment elevation myocardial infarction [STEMI]: IRR: 0.76, P = .001; non-STEMI: IRR: 0.74, P < .001; and unstable angina [UA]: IRR: 0.63, P = .002). The decrease in STEMI admissions was stable throughout the COVID-19 period (temporal correlation; R2 = 0.11, P = .53), whereas there was a gradual decline in non-STEMI/UA admissions (R2 = 0.75, P = .026) following the progressively stricter social measures. During the COVID-19 period, patients admitted with ACS presented more frequently with left ventricular systolic impairment (22.2 vs 15.5% control period; P < .001). CONCLUSIONS: We observed a reduction in ACS hospitalizations during the COVID-19 outbreak in a country with strict social measures, low community transmission, and no excess in mortality. Medical care avoidance behavior is an important factor for these observations, while a true reduction of the ACS incidence due to self-isolation/quarantining may have also played a role.

HEllenic Registry on Myocarditis SyndromES on behalf of Hellenic Heart Failure Association: The HERMES-HF Registry.

AIMS: Despite the existence of many studies, there are still limited data about the characteristics of myocarditis in Greece. This led to the creation of the Greek Myocarditis Registry aiming to document the different symptoms and treatment of myocarditis, assess possible prognostic factors, and find similarities and differences to what is already published in literature. This paper is a preliminary descriptive analysis of this Registry. METHODS AND RESULTS: We analysed data for the hospitalization period of all patients included in the Registry from December 2015 until November 2017. Statistics are reported as frequency (%) or median and inter-quartile range (IQR) as appropriate. In total, 146 patients were included; 83.3% of the patients reported an infection during the last 3 months. The most common symptom, regardless of the underlying infection, was chest pain (82.2%) followed by dyspnoea (18.5%), while the most common finding in clinical examination was tachycardia (26.7%). Presentation was more frequent in the winter months. ECG findings were not specific, with the repolarization abnormalities being the most frequent (60.3%). Atrial fibrillation was observed in two patients, both of whom presented with a reduced ventricular systolic function. Left ventricular ejection fraction changed significantly during the hospitalization [55% (IQR: 50-60%) on admission vs. 60% (IQR: 55-60%) on discharge, P = 0.0026]. Cardiac magnetic resonance was performed in 88 patients (61%), revealing mainly subepicardial and midcardial involvement of the lateral wall. Late gadolinium enhancement was present in all patients, while oedema was found in 39 of them. Only 11 patients underwent endomyocardial biopsy. Discharge medication consisted mainly of beta-blockers (71.9%) and angiotensin-converting enzyme inhibitors (41.8%), while 39.7% of the patients were prescribed both. CONCLUSIONS: This preliminary analysis describes the typical presentation of myocarditis patients in Greece. It is a first step in developing a better prognostic model for the course of the disease, which will be completed after the incorporation of the patients' follow-up data.

Association of VEGF gene polymorphisms with the development of heart failure in patients after myocardial infarction.

OBJECTIVES: Vascular endothelial growth factor (VEGF) is upregulated in vivoin the ischemic human myocardium. Since several polymorphisms have been shown to influence VEGF expression, we evaluated the contribution of such polymorphisms to the clinical outcome of patients after an acute myocardial infarction (AMI). METHODS: PCR and restriction fragment length polymorphism analysis was performed to genotype 10 VEGF polymorphisms in 102 patients who had suffered an AMI and in 98 age- and sex-matched healthy individuals. Distribution of these polymorphisms was assessed by logistic regression analysis. RESULTS: No significant differences were found between patients and normal individuals. However, when patients were subdivided into 2 groups based on the development of heart failure after their AMI judged by heart ultrasound measurements (ejection fraction <40%), the distribution of the -634 polymorphism differed significantly (p = 0.016). Specifically, patients with a CC genotype had 7 times higher risk of developing heart failure. Additionally, the co-inheritance of -634 with other VEGF polymorphisms was found to be significant for the development of heart failure between these 2 groups. CONCLUSIONS: Our data indicate that the -634 polymorphism and its co-inheritance with genotypes of other VEGF polymorphisms might be considered as risk factors playing a role in the clinical outcome of AMI patients.