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.

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.

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.

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.

Management of iron deficiency in chronic heart failure: Practical considerations for clinical use and future directions.

Heart Failure (HF) is a global pandemic with rapidly increasing prevalence. In an attempt to maintain patients well being, the therapeutic interest has expanded to the vicious cycles that confer to HF mortality and morbidity and a number of comorbidities have been targeted. Iron deficiency represents a common comorbid condition that affects outcomes in HF. The treatment of iron deficiency is strongly supported by the cardiologic societies all over the world. Intravenous iron, primarily ferric carboxymaltose, has shown clinical benefit in this setting, irrespective of the anemia status. Practical recommendations though are lacking. In this document, we have tried to cover the practical gap and provide useful details for intravenous iron use.

Prevention of Radial Artery Occlusions Following Coronary Procedures: Forward and Backward Steps in Improving Radial Artery Patency Rates.

Radial artery (RA) occlusion (RAO) remains the Achilles heel of transradial coronary procedures. Although of silent nature, RAO is relatively frequent, results in graft shortage for future coronary artery bypass surgery, and may occur even after short-lasting, 5F coronary angiography (CAG). The most frequent predictors of RAO are RA size, body size, female gender, and periprocedural anticoagulation intensity. Methods to detect RAO are variable, of which the Barbeau test and ultrasonography have similar diagnostic accuracy. Data indicate that late RAO recanalization may occur. Meticulous handling of RA and the use of appropriate hemostatic devices and techniques along with sufficient heparin dose appear important measures to reduce RAO rates. Recent contradictory studies indicate that the decreasing incidence of RAO overtime is not as uniform as previously thought. In 2 meta-analyses, the benefit of higher over lower anticoagulation intensity became evident. As "it may all be appropriate anticoagulation" for a simplified approach against RAO, the results of an ongoing trial comparing 100 with 50 IU/kg body weight in transradial CAG are eagerly awaited.

Needle versus cannula over needle for radial artery cannulation during transradial coronary angiography and interventions.

PURPOSE: To evaluate the efficacy of radial artery cannulation with needle versus cannula over needle during transradial coronary angiography and intervention. METHODS: Five hundred patients scheduled to undergo transradial catheterization were randomized between the two methods. Primary endpoint of the study was the combined endpoint of switching to another access site due to inability of successful sheath insertion or switching to another method of cannulation (from needle to cannula over needle and vice versa). RESULTS: The primary end point was met in 12 patients (4.8%) from the needle group and 14 patients (5.6%) from the cannula over needle group (p=0.695). There were no differences in switching of cannulation method [10 (4.0%)% versus 11 (4.4%), p=0.831], switching of access site [6 (2.8%) versus 9 (3.6%), p=0.441), time for artery cannulation [1.20 (0.80-2.20) min versus 1.26 (1.01-2.39) min, p=0.152], total procedure time [15.05 (9.47-29.03) min versus 19.14 (10.13-32.02) min, p=0.112] number of attempts [2 (1-4) versus 2 (1-5), p=0.244] and number of skin punctures [1 (1-2) versus 1 (1-2), p=0.399] before successful radial artery cannulation. There were no differences recorded in the safety endpoints of EASY grade III or more radial hematomas [2 (0.8%) versus 1 (0.4%), p=1.000] or the incidence of radial artery occlusion after the procedure [9 (3.6% versus 16 (6.8%), p=0.358]. CONCLUSION: Radial artery cannulation with needle and cannula over needle seems to be equal in terms of efficacy and safety.

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.

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 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.

Acute myocardial infarction in a patient with coronary artery aneurysm and Crohn's disease.

Crohn's disease is a chronic inflammatory disorder of unknown cause involving the gastrointestinal tract. Complications from the cardiovascular system seem to be uncommon in patients with Crohn's disease. We present a case of a 37-year-old man with a known history of Crohn's disease, who was admitted to our hospital with acute myocardial infarction. An aneurysm of a totally occluded circumflex coronary artery was revealed during the attempt at primary intervention. The artery was successfully opened and the aneurysm was sealed with the use of 2 covered stents.

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.

Procalcitonin in acute myocardial infarction.

OBJECTIVE: Procalcitonin (PCT) is released in severe bacterial infections, sepsis and in infection independent cases such as major surgery, multiple trauma, cardiogenic shock, burns, resuscitation, and after cardiac surgery. The aim of this study was to determine the levels and the kinetics of PCT in AMI and to investigate their possible correlation with the release of IL-6 and CRP. DESIGN-PATIENTS: The study included 60 patients (47 men, 63.2+/-14.8 years) with the diagnosis of AMI at admission. In all patients, serum levels of PCT, IL-6, CK-MB, TnI and CRP were measured at admission, at 3, 6, 12, 24, 48 and 72 h and at the seventh day. RESULTS: PCT was elevated in all patients with AMI. It was initially detected in serum approximately 2-3 h after the onset of the symptoms. The median value at admission was 1.3 ng/ml (95% CI: 0.89 to 1.80). The value of PCT showed an increase and reached a plateau after 12-24 h. The median value at 24 h was 3.57 ng/ml (95% CI: 2.89 to 4.55). PCT values fell to baseline (<0.5 ng/ml) by the seventh day. PCT was detected in serum earlier than CK-MB or TnI in 56 of the 60 patients (93.3%). The kinetics of PCT was similar to those of CK-MB and TnI. The maximal values of PCT were positively correlated with the maximal values of IL-6 (r = 0.59, P = 0.00) and of CRP (r = 0.65, P = 0.001). The maximal values of IL-6 were positively correlated with max CRP (r = 0.35, P = 0.045). CONCLUSIONS: PCT could be considered as a novel sensitive myocardial index. Its release in AMI is probably due to the inflammatory process that occurs during AMI.

Adenosine stress myocardial perfusion tomographic imaging in patients with significant aortic stenosis.

BACKGROUND: Myocardial perfusion scintigraphy has been used by some investigators for the diagnosis of coronary artery disease (CAD) in patients with mild, moderate, and moderate to severe aortic stenosis, with various results. The aim of this study was to assess the safety and diagnostic accuracy of adenosine stress myocardial perfusion scintigraphy (adenosine single photon emission computed tomography [Ad-SPECT]) for the detection of CAD in patients with significant aortic stenosis. METHODS AND RESULT: The study included 75 patients with significant aortic stenosis (maximal instantaneous aortic valve gradient >80 mm Hg [range, 81-149 mm Hg] and aortic valve area <0.75 cm2). All patients underwent Ad-SPECT after a 6-minute infusion of adenosine (140 microg/kg body weight per minute). At the third minute of adenosine infusion, a bolus of 3 mCi thallium 201 was injected, and SPECT acquisition was obtained immediately after completion of adenosine infusion. Coronary angiography was performed in all patients. No major complications during adenosine infusion were observed. All unpleasant symptoms lasted for only a few seconds and did not necessitate cessation of the test. Concerning the angiographically diagnosed CAD, we found that Ad-SPECT showed a sensitivity of 88.6%, a specificity of 72.5%, a positive predictive value of 73.8%, a negative predictive value of 87.8%, and a diagnostic accuracy of 80%. CONCLUSIONS: Ad-SPECT is a moderately accurate method for detecting the presence or absence of CAD in patients with severe aortic stenosis. However, further modification of this method is required before it can supplant cardiac catheterization in the preoperative evaluation of patients with severe aortic stenosis.