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This prospective, first-in-man, open-label multicenter study sought to assess the pharmacokinetics of sirolimus after Ultimaster drug-eluting stent implantation (coated with sirolimus and bioabsorbable co-polymer) in patients with de novo coronary artery disease (the TCD-10023 PK study). The primary endpoint was sirolimus concentration in peripheral whole blood at 28 days after stent implantation. In addition, safety, tolerability, therapeutic outcome and vasomotor response after stent implantation were studied. Twenty patients were enrolled in the study. Blood samples for the measurements of sirolimus concentration were collected at eight time points during first 48 h, at 7 days and 28 days after stent implantation. Patients underwent 6-month angiographic and up to 12 months clinical follow-up. At 28 days, only two of 20 patients had sirolimus concentrations above lower limit of quantification (20.0 pg/mL). The highest sirolimus blood concentration was 105 pg/mL. The median maximum concentration was 36.8 pg/mL (range 22.9-41.5 pg/mL) for stent 3.0 × 15 mm and 87.2 pg/mL (range 60.0-105.0 pg/mL) for 3 × 28 mm stent. The median systemic exposure, as measured by the area under the time-concentration curve, was 8.3 ng h/mL (range 6.47-28.0 ng h/mL). At 6 months, endothelial function was well preserved, and up to 12 months, there were no signs of sirolimus toxicity nor any other safety concerns. Our results demonstrate that implantation of Ultimaster stent resulted in almost nondetectable sirolimus in blood after 28 days. These findings were translated into exceptional safety profile, without any sign of systemic toxicity.

Background/Aim. Long-term intensive training is associated with distinctive cardiac adaptations which are known as athlete?s heart. The aim of this study was to determine whether the use of anabolic androgenic steroids (AAS) could affect echocardiographic parameters of left ventricular (LV) morphology and function in elite strength and endurance athletes. Methods. A total of 20 elite strength athletes (10 AAS users and 10 non-users) were compared to 12 steroid-free endurance athletes. All the subjects underwent comprehensive standard echocardiography and tissue Doppler imaging. Results. After being indexed for body surface area, both left atrium (LA) and LV end-diastolic diameter (LVEDD) were significantly higher in the endurance than strength athletes, regardless of AAS use (p < 0.05, for both). A significant correlation was found between LA diameter and LVEDD in the steroid-free endurance athletes, showing that 75% of LA size variability depends on variability of LVEDD (p < 0.001). No significant differences in ejection fraction and cardiac output were observed among the groups, although mildly reduced LV ejection fraction was seen only in the AAS users. The AAS-using strength athletes had higher A-peak velocity when compared to steroidfree athletes, regardless of training type (p < 0.05 for both). Both AAS-using and AAS-free strength athletes had lower e? peak velocity and higher E/e? ratio than endurance athletes (p < 0.05, for all). Conclusions. There is no evidence that LV ejection fraction in elite athletes is altered by either type of training or AAS misuse. Long-term endurance training is associated with preferable effects on LV diastolic function compared to strength training, particularly when the latter is combined with AAS abuse.

In a few patients with acute proximal thrombotic occlusion of the left anterior descending coronary artery (LAD), tall ischemic T waves never evolve into ST-segment elevation. This was recently inaccurately reported as a "novel sign" of proximal LAD occlusion. It has been speculated that the absence of ST-segment elevation could be attributed to the large area of transmural ischemia, the anatomic variant of Purkinje fibers, or to lack of activation of sarcolemal adenosine triphosphate-potassium channels. This electrocardiographic picture was recently explained by changes in the subendocardial but not in the epicardial action potential, suggesting subendocardial ischemia as the underlying mechanism. We present a patient with thrombotic lesion of proximal LAD, static precordial ST-segment depression, and tall T waves who underwent primary percutaneous intervention and stent placement. Surprisingly, total thrombotic stent occlusion on the following day was associated with ST-segment elevation in precordial leads, indeed supporting the concept of the regional subendocardial ischemia that was first described more than a decade ago.

Background: Simvastatin, a 3-hydroxy-3-methylglutarylcoenzyme A reductase inhibitor, is indicated for the treatment of hypercholesterolemia and plays an important role in both the primary and secondary prevention of cardiovascular disease. Danazol is a steroid analogue approved for the treatment of endometriosis, fibrocystic breast disease, and hereditary angioedema. Despite not being licensed, danazol has been used for other off-label indications, such as idiopathic thrombocytopenic purpura (ITP), paroxysmal nocturnal hemoglobinuria, and aplastic anemia. Objective: We report a case of fatal rhabdomyolysis that occurred after concomitant administration of simvastatin and danazol in a patient with ITP. Case summary: An 80-year-old white male (height, 182 cm; weight, 90 kg) presented to the emergency department of the Clinical Hospital Centre Zemun, Belgrade, Serbia, with head injuries after an accidental fall caused by generalized weakness. He denied other complaints, except fatigue, mild pretibial edema, and progressive bilateral leg pain and cramping that began 7 days before. At the time of presentation, he was receiving aspirin 100 mg/d, clopidogrel 75 mg/d, ramipril 2.5 mg/d, pantoprazole 40 mg/d, danazol 600 mg/d, prednisone 60 mg/d, simvastatin 40 mg/d, and longacting insulin 24 IU/d. After the injuries were treated, he was diagnosed with collapse and nasal contusion, and discharged without any changes in his therapy. Two days after initial presentation, the patient was readmitted to the hospital due to nausea, dark urine, and oliguria. All clinical signs (oliguria, dark urine, muscle pain, and tenderness) and laboratory markers (creatine kinase levels ∼100 times the upper limit of normal, along with hyperkalemia, hyperphosphatemia, and hypoalbuminemia) were consistent with severe rhabdomyolysis. Despite intravenous hydration, forced diuresis, and hemodialysis, oliguria persisted and the patient died 6 days after admission. A score of 5 on the Naranjo adverse drug reaction probability scale was consistent with a probable association of rhabdomyolysis and concomitant treatment with simvastatin and danazol in this patient. Conclusions: Statin-induced rhabdomyolysis must be considered whenever muscle or motor symptoms occur, especially when concomitant treatment with known inhibitors of statin metabolism is administered. Patients must be strictly monitored and the statin should be promptly discontinued with the onset of first signs and symptoms of myopathy. Clinicians should be aware of the potentially fatal consequences of both approved and unapproved treatments and be alert for the early detection of toxicity.

Introduction. Pacemaker syndrome consists of the symptoms and signs present in the single chamber (VVI) pacemaker patient with electrode placed in the right ventricular apex. It is caused by inadequate timing of atrial and ventricular contractions. Pacemaker syndrome without a pacemaker (or pseudopacemaker syndrome) refers to occurrence of symptoms in the presence of marked first-degree atrioventricular (AV) block, when P wave is too close to the preceding QRS complex producing the same haemodynamic disturbance as artificial pacemaker cardiac stimulation with retrograde VA conduction. Case Outline. We present the patient with acute inferior myocardial infarction due to late bare metal stent thrombosis, treated with primary pectutaneous coronary intervention. Hospital course was complicated by complete heart block which was treated with temporary pacing. During the stand-by mode of temporary pacing, sinus rhythm with marked first-degree AV block (PQ interval 480 ms) was observed while the patients re-experienced the symptoms that were present prior to pacemaker implantation. Temporary pacing was continued for the next 24 hours when spontaneous shorteninig of PQ interval (250-270 ms) was noticed; since the patient was asymptomatic during the stand-by mode, the pacemaker electrodes were removed and the patient discharged 11 days after admission. Conclusion. Conduction disturbances, such as the varying degrees of AV blocks, are relatively common in acute inferior myocardial infarction. The first degree AV blok is usually asymptomatic and does not require treatment, unless when it is associated with pseudopacemaker syndrome. In that case, temporary pacing provides haemodynamic stability until conduction system recovers.

Objective The goal of the current work was to assess the possible relationship between upright T wave in precordial lead V1 (TV1) and the occurrence of coronary artery disease (CAD) in patients undergoing coronary angiography with an otherwise unremarkable resting electrocardiogram (ECG). Methods Twelve-lead resting ECGs of 2,468 patients who underwent coronary angiography were analyzed by independent reviewers blinded to the patients' clinical data. Patients with any condition known to affect cardiac repolarization were not eligible for inclusion. Results Of 126 patients included in the study, 76 (60%) had at least one significant coronary artery stenosis. Significant CAD was more frequently found in patients with upright TV1 as compared to those with negative TV1 (74 vs. 43%, p = 0.001). Left circumflex (LCx) and left anterior descending (LAD) coronary artery lesions were more frequently observed in patients with upright TV1 than in those with inverted TV1. In univariate analysis, patients with upright TV1 were approx 4 times more likely to have significant CAD than those with inverted TV1 (odds ratio (OR) 3.7, 95% confidence interval (CI) 1.744-7.897). In addition, in the multivariate logistic regression model, upright TV1 was an independent predictor of significant CAD (OR 4.249, 95% CI 1.594-11.328), along with previous myocardial infarction (OR 17.533, 95% CI 3.338-92.091), male gender (OR 3.020; 95% CI 1.214-7.510), and age (OR 1.061; 95% CI 1.003-1.122). Conclusion It might be worthwhile to routinely evaluate the polarity of the T wave in lead V1 in patients with suspected CAD, since it appears to have additional risk stratification potential.

Background Wellens syndrome refers to a distinct electrocardiographic pattern of deeply inverted or biphasic T waves in the anterior precordial leads, in the presence of critical proximal stenosis of the left anterior descending coronary artery (LAD). The natural history of the syndrome is an extensive myocardial infarction within weeks of hospital admission. Case Report This report describes a 63-year-old man in whom typical electrocardiographic signs of Wellens syndrome advanced to persistent ST-segment elevation within 7 min of presentation. Extensive anterior myocardial infarction (AMI) was aborted by primary percutaneous coronary intervention of a sub-occluded proximal LAD. Conclusion Given the large area of the left ventricle supplied by a sub-occluded LAD, devastating AMI could have been expected and may have resulted in serious ventricular dysfunction and death. Therefore, early recognition of Wellens syndrome is essential and can be lifesaving.

BACKGROUND Gestational hypertension (GH) is associated with hemodynamic changes, and alterations of systolic and diastolic left ventricular (LV) function. However, the magnitude and pattern of changes of different parameters of LV function and contractility in this patient population have not been fully clarified. METHODS Thirty-five pregnant women with GH underwent three echocardiographic examinations, in second and third trimester of pregnancy, and 1 month after delivery. Twelve normotensive pregnant women served as gestational age-matched controls. Hemodynamic parameters and standard indexes of LV systolic and diastolic function were analyzed. Additionally, we have measured peak systolic velocity of mitral annulus (S'), end-systolic elastance (Ees), and early transmitral to early lengthening velocity of mitral annulus ratio (E/E') as parameters of longitudinal function, contractility, and filling, respectively. RESULTS Women with GH had initially higher body weight, blood pressure, and heart rate (P < 0.005, P < 0.0001, and P = 0.011, respectively). Temporal analysis of different echocardiographic parameters revealed increase in wall thickness from baseline to second measurement, with consequential increase in LV mass in women with GH (P = 0.014 for septum, P = 0.010 for posterior wall, and P = 0.09 for LV mass). No significant changes of LV volumes, ejection fraction (EF), transmitral flow parameters, S', Ees, and E/E' were observed throughout the follow-up in both groups (P = nonsignificant for all). Importantly, pattern of changes was similar in both groups for all examined parameters (P = nonsignificant between groups, for all). CONCLUSIONS It appears that changes of LV longitudinal function, filling, and contractility during pregnancy are not significant and not influenced by GH.

To compare head to head the indices of left ventricular contractile reserve assessed by high-dose dobutamine in the five-year prognosis of patients with idiopathic dilated cardiomyopathy.Prospective study in a tertiary care centre.63 consecutive patients with idiopathic dilated cardiomyopathy.High-dose dobutamine stress echocardiography was performed in progressive stages lasting 5 min each. Wall motion score index, ejection fraction, cardiac power output and end systolic pressure to volume ratio were evaluated as indices of left ventricular contractility.Five-year cardiac mortality.During the follow up of 59 patients, 27 (45.8%) died of cardiac causes. According to Kaplan-Meier and receiver operating characteristic analyses all indices of contractile reserve differentiated patients with respect to cardiac death. Wall motion score index achieved the best separation (log rank 21.75, p0.0001, area under the curve 0.84), followed by change in ejection fraction (log rank 11.25, p = 0.0008, area under the curve 0.79), end systolic pressure to volume ratio (log rank 14.32, p = 0.0002, area under the curve 0.75) and cardiac power output (log rank 9.84, p = 0.0017, area under the curve 0.71). Cox's regression model identified wall motion score index as the only independent predictor of cardiac death.These data show that all examined indices of left ventricular contractile reserve are predictive of five-year prognosis, but change in wall motion score index may have the greatest prognostic potential.