Sotirios Patsilinakos

Cell‐Free DNA Levels as a Prognostic Marker in Acute Myocardial Infarction

Abstract:  Cell‐free DNA that originates from cell death, circulates in peripheral blood. There are indications that the infarcted myocardium contributes to an increase of cell‐free DNA levels. Our aims were to quantify levels of cell‐free DNA in patients with acute myocardial infarction (AMI) and examine their correlation with myocardial markers and with postinfarction (PI) clinical course. Thirteen patients (age 57 ± 16 year) admitted with AMI and who underwent thrombolysis with reteplase within 6 h from the onset of chest pain were studied. PB samples were collected on admission and for 5 consecutive days. Creatine kinase (CK) and troponin I (TnI) were measured on admission and every 8 h for 3 consecutive days. Clinical events were recorded throughout the hospitalization period. Cell‐free DNA levels were also measured in 30 healthy controls. Log‐transformed mean (±SE) of maximum free DNA values in patients higher than controls (6873 ± 357 g.e./mL verses 4112 ± 234 g.e./mL, P < 0.0001). Log‐transformed maximum values of CK and TnI were correlated with log‐transformed free DNA values of first (r= 0.62, P= 0.02/r= 0.68, P= 0.01) and second (r= 0.57, P= 0.04/r= 0.72, P= 0.0053) PI day. Nine patients (group A) had an uncomplicated PI clinical course and four patients (group B) had recorded events (three with angina and one death). Free DNA levels on the second PI day were higher in group B than group A (1298.0 ± 796.0 g.e./mL verses 244.6 ± 257.7 g.e./mL, P= 0.003). In conclusion, free DNA levels are significantly higher in patients with AMI than in controls and may play a role in the prognosis of these 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.

Double Versus Standard Loading Dose of Ticagrelor : Onset of Antiplatelet Action in Patients With STEMI Undergoing Primary PCI

To the Editor: Early and strong platelet inhibition is highly desirable in patients with ST-segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PCI). Ticagrelor, which has direct action on the P2Y12 receptor and no need for previous metabolic

CorrespondenceResearch CorrespondenceDouble Versus Standard Loading Dose of Ticagrelor: Onset of Antiplatelet Action in Patients With STEMI Undergoing Primary PCI

To the Editor: Early and strong platelet inhibition is highly desirable in patients with ST-segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PCI). Ticagrelor, which has direct action on the P2Y12 receptor and no need for previous metabolic

Effect of High Doses of Magnesium on Converting Ibutilide to a Safe and More Effective Agent

Ibutilide is a class III antiarrhythmic agent indicated for cardioversion of atrial fibrillation and atrial flutter to sinus rhythm (SR). The most serious complication of ibutilide is torsades de pointes (TdP). Magnesium has been successfully used for the treatment of TdP, but its use as a prophylactic agent for this arrhythmia has not yet been established. The present study investigated whether high dose of magnesium would increase the safety and efficacy of ibutilide administration. A total of 476 patients with atrial fibrillation or atrial flutter who were candidates for conversion to SR were divided into 2 groups. Group A consisted of 229 patients who received ibutilide to convert atrial fibrillation or atrial flutter to SR. Group B consisted of 247 patients who received an intravenous infusion of 5 g of magnesium sulfate for 1 hour followed by the administration of ibutilide. Then, another 5 g of magnesium were infused for 2 additional hours. Of the patients in groups A and B, 154 (67.3%) and 189 (76.5%), respectively, were converted to SR (p = 0.033). Ventricular arrhythmias (sustained, nonsustained ventricular tachycardia, and TdP) occurred significantly more often in group A than in group B (7.4% vs 1.2%, respectively, p = 0.002). TdP developed in 8 patients (3.5%) in group A and in none (0%) in group B (p = 0.009). The administration of magnesium (despite the high doses used) was well tolerated. In conclusion, the administration of high doses of magnesium probably makes ibutilide a much safer agent, and magnesium increased the conversion efficacy of ibutilide.

Detection of Coronary Artery Disease in Patients with Severe Aortic Stenosis with Noninvasive Methods

Exercise stress ECG testing is not generally recommended in patients with severe aortic stenosis. Analysis of the utility of exercise testing, both with and without the use of myocardial thallium-201 scintigraphy for the diagnosis of coronary artery disease (CAD), yielded low specificity. A noninvasive, safe, and accurate diagnostic modality to ascertain the presence of CAD is not available to date for patients with severe aortic stenosis. The aim of this study was to assess the safety and diagnostic accuracy of adenosine stress echocardiography (A-Stress-Echo) and of adenosine stress myocardial perfusion scintig raphy (A-SPECT), for the detection of CAD in patients with severe aortic stenosis. The study included 50 patients with severe aortic stenosis (maximal instantaneous aortic valve gradient > 80 mmHg, range 81 to 144 mmHg, and aortic valve area < 0.75 cm2). All patients were submitted to A-Stress-Echo, after a 6-minute infusion of adenosine (140 μg/kg body weight/min), and then (>3 days later) A-SPECT with the same dosage of adenosine as above. Coronary angiography was performed in all patients. No major complications were observed. The unpleasant symptoms were brief and did not necessitate cessation of the test. Both modalities showed the same sensitivity (85% for A-SPECT and 85% for A-Stress-Echo) angiographically diagnosed CAD while A-Stress-Echo yielded much higher specificity (96.7% vs 76.7%). Concordance of the two methods was found in 40 cases and the specificity for those patients was 100%. A-Stress-Echo and A-SPECT, either separately or in combination, constitute excellent and safe noninvasive diagnostic methods in detecting CAD in patients with severe aortic stenosis.

Sealing of coronary artery aneurysm by using a new stent graft.

Coronary stenting has begun to play an increasingly important role in the management of coronary artery aneurysms. A case of successful and complete sealing of a coronary aneurysm by using a new stent graft is described. Further studies in a large patient population are required to confirm the safety and efficacy of this method. Cathet. Cardiovasc. Intervent. 48:96–99, 1999.

Coronary microcirculation evaluation with transesophageal echocardiography Doppler in type II diabetics

Evaluation of coronary microvascular function can be obtained through coronary flow reserve measurements. The aim of this study was to evaluate the coronary microvascular function by using transesophageal-Doppler echocardiographic assessment of coronary flow reserve. The study included 32 normotensive patients with type II diabetes mellitus (group A) of short duration (6.1+/-3.8 years) aged 55.4+/-9.4 years and 14 healthy volunteers matched for age, gender and BMI (group B). No patients had clinical evidence of coronary artery disease and all of them produced a negative recent stress ECG test. Excluded from the study were patients with anemia, left ventricular hypertrophy, arrhythmia, congenital, or acquired structural heart disease. All subjects underwent transesophageal-Doppler echocardiography. Satisfactory coronary blood flow velocity recordings could be obtained from the initial segment of the left anterior descending coronary artery in healthy volunteers and in 27 patients at baseline and 2 min after dipyridamole infusion (0.56 mg/kg, for 4 min). In the remaining 5 patients no satisfactory recordings were available. The indexes of coronary flow reserve, i.e. the ratios of dipyridamole over basal maximum and mean diastolic velocities were calculated. Dipyridamole/rest maximal coronary reserve (Table 3) was 1.946+/-0.743, while this ratio for the mean diastolic velocity was 1.969+/-0.805 in group A. The respective values for group B, were 2.811+/-0.345 (P=0.000 vs. group A) and 2.914+/-0.303 (P=0.000 vs. group A). Thus, the increase in coronary flow reserve although present in both groups, it was more impressive in the normal group. Multiple regression logistic analysis of: age, sex, smoking, glucosylated hemoglobin, duration of diabetes and type of therapy, did not show any correlation of these parameters with the above ratios. This study shows that coronary flow reserve, as measured with transesophageal echocardiography-Doppler, is severely impaired in normotensive patients with type II diabetes, with relatively short duration of the disease.

Onset of Antiplatelet Action With High (100 mg) Versus Standard (60 mg) Loading Dose of Prasugrel in Patients With ST-Segment–Elevation Myocardial Infarction Undergoing Primary Percutaneous Coronary Intervention Pharmacodynamic Study

Background—In patients with ST-segment–elevation myocardial infarction undergoing primary percutaneous coronary intervention, a suboptimal degree of platelet inhibition for the first 2 hours after the standard 60 mg loading dose of prasugrel has been described. Methods and Results—In a prospective, 3-center, nonrandomized, controlled study, 2 sequential groups of P2Y12 inhibitor-naive consecutive patients were loaded with either 100 mg (n=47) or 60 mg (n=35) of prasugrel. Platelet reactivity was assessed by VerifyNow at hours 0, 0.5, 1, 2, and 4. At hour 2, there was a strong trend for the primary end point of platelet reactivity (in P2Y12 reaction units) to be lower (least squares estimates of the mean difference [95% confidence interval], −45.5 [−91.2 to 0.3]; P=0.051), whereas platelet reactivity percentage inhibition (median, first to third quartile) was higher (75.5% [24%–91.8%] versus 23.5% [0%–78.3%]; P=0.02) in the 100-mg compared with 60-mg loading dose group. At hour 2, prasugrel 100 mg over 60 mg loading dose significantly reduced high platelet reactivity rates from 28.6% to 8.5% (≥230 P2Y12 reaction units threshold; P=0.036) and from 31.4% to 10.6% (≥208 P2Y12 reaction units threshold; P=0.024), whereas resulted in lower rate of ⩽20% platelet inhibition (23.4% versus 51.4%; P=0.009). Conclusions—In patients with ST-segment–elevation myocardial infarction treated with primary percutaneous coronary intervention, a higher (100 mg) than the standard loading dose of prasugrel results in greater and more consistent platelet inhibition, yet this will need to be further validated in additional studies. Clinical Trial Registration—URL: http://www.clinicaltrials.gov. Unique identifier: NCT01835353.

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.