Pharmacodynamic Effects of Pre-Hospital Administered Crushed Prasugrel in Patients With ST-Segment Elevation Myocardial Infarction

ObjectivesThis study sought to compare the pharmacodynamic effects of pre-hospitally administered P2Y₁₂ inhibitor prasugrel in crushed versus integral tablet formulation in patients with ST-segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (pPCI).BackgroundEarly dual antiplatelet therapy is recommended in STEMI patients. Yet, onset of oral P2Y₁₂ inhibitor effect is delayed and varies according to formulation administered.MethodsThe COMPARE CRUSH (Comparison of Pre-hospital Crushed Versus Uncrushed Prasugrel Tablets in Patients With STEMI Undergoing Primary Percutaneous Coronary Interventions) trial randomized patients with suspected STEMI to crushed or integral prasugrel 60-mg loading dose in the ambulance. Pharmacodynamic measurements were performed at 4 time points: before antiplatelet treatment, at the beginning and end of pPCI, and 4 h after study treatment onset. The primary endpoint was high platelet reactivity at the end of pPCI. The secondary endpoint was impact of platelet reactivity status on markers of coronary reperfusion.ResultsA total of 441 patients were included. In patients with crushed prasugrel, the occurrence of high platelet reactivity at the end of pPCI was reduced by almost one-half (crushed 34.7% vs. uncrushed 61.6%; odds ratio [OR] = 0.33; 95% confidence interval [CI] = 0.22 to 0.50; p < 0.01). Platelet reactivity <150 P2Y₁₂ reactivity units at the beginning of coronary angiography correlated with improved Thrombolysis In Myocardial Infarction flow grade 3 in the infarct artery pre-pPCI (OR: 1.78; 95% CI: 1.08 to 2.94; p = 0.02) but not ST-segment resolution (OR: 0.80; 95% CI: 0.48 to 1.34; p = 0.40).ConclusionsOral administration of crushed compared with integral prasugrel significantly improves platelet inhibition during the acute phase in STEMI patients undergoing pPCI. However, a considerable number of patients still exhibit inadequate platelet inhibition at the end of pPCI, suggesting the need for alternative agents to bridge the gap in platelet inhibition.     

Coronary laser thermal angioplasty in the swine: reduced complications with shorter laser delivery time

Although laser thermal angioplasty (LTA) with a laser heated metal probe has been tolerated in diseased human coronary arteries, definition of a safety threshold is lacking. Determination of safer operation parameters for coronary LTA using a new "over the wire" 1.3-mm laser probe catheter was attempted in seven normal pigs in which platelets were labeled with indium-111. Argon laser power of 10 watts was used for 1, 2, 3, and 5 seconds. Macroscopic findings, platelet deposition and histologic changes were compared between the laser treated coronary segments and controls, the nonheated laser probe, and the wire alone segments. After 1-second LTA, there was no vessel perforation or occlusive thrombi and only infrequent nonocclusive thrombi; platelet deposition was minimal; and histologic alterations rare and superficial. These findings were comparable to controls, the nonheated laser probe, and the wire alone segments. In contrast, vessels treated for 2, 3, and 5 seconds had more frequent perforation, and occlusive and nonocclusive thrombi that was accompanied by platelet deposition significantly greater than vessels treated with LTA for 1 second. A deep histologic injury was present in most of these segments. Additionally, the safety of laser delivery of 1 second repeated for five times was tested in two additional pigs. On macroscopic and histologic analysis the incidence of vessel perforation, occlusive and nonocclusive thrombi appeared slightly less when compared to the 2-, 3-, and 5-second LTA groups, and more than the 1-second LTA group.(ABSTRACT TRUNCATED AT 250 WORDS)     

The 24-hour heart rate behavior in long-term survivors of cardiac transplantation

A detailed computerized analysis of heart rate (HR) behavior during ambulatory monitoring was performed in 19 long-term survivors of cardiac transplantation (12 orthotopic, 7 heterotopic) and in 10 normal volunteers. Compared with normal hearts, the transplanted denervated and the recipient innervated hearts in the heterotopic group showed higher average HRs over the whole 24 hours, the waking and sleeping periods. The rates of the denervated and the recipient hearts did not differ significantly. The maximal HR was similar in all 3 groups, but the minimal HR was lower in the normal hearts than in denervated and recipient hearts. The 24-hour RR interval variability was greatly reduced in the denervated hearts (60 +/- 22 ms) compared with the recipient (89 +/- 26 ms) and normal (151 +/- 38 ms) hearts. During arousal from sleep, the magnitude, time and rate of the HR change were significantly reduced in the denervated hearts compared with the innervated hearts and in the recipient compared with the normal hearts. These findings demonstrate that denervated hearts can show significant variations in HR during the 24-hour period, but to a lesser extent than normal hearts. The widest deviation from normal occurs during sleep, when the denervated heart shows minimal slowing probably due to lack of parasympathetic innervation. In heterotopic transplant recipients, the patients' own HR responses also are significantly blunted.     

Coronary calcium detected by digital cinefluoroscopy and coronary artery disease in patients undergoing coronary arteriography: effects of age and sex

BACKGROUND: Coronary artery calcium, detected non-invasively, correlates well with angiographically documented coronary artery disease (CAD). This study was conducted to evaluate the diagnostic efficacy of coronary artery calcium detected by digital cinefluoroscopy for CAD and assess the effects of age and sex on it. METHODS: In 242 patients who underwent coronary angiography, coronary calcium status was determined and related to angiographic findings. RESULTS: Calcium detection had a sensitivity 85%, specificity 52%, positive predictive value 92%, negative predictive value 33% and diagnostic accuracy 81% for significant CAD. There was a better positive predictive value in men (95% vs. 80%) and negative predictive value in women (65% vs. 16%), while a higher sensitivity and diagnostic accuracy was found in older than in younger (90% and 86% vs. 78% and 74%). The sensitivity of the method increased with the number of the diseased vessels. CONCLUSIONS: Coronary calcium can be quite accurately detected by digital cinefluoroscopy. This, however, should be made in the context of sex and age.     

ST-segment depression during vasodilator stress is of minor clinical importance in women with normal myocardial perfusion imaging and low or intermediate risk of coronary artery disease

Purpose  

The prognostic value of electrocardiographic (ECG) ST-segment depression during vasodilator stress testing in patients with normal myocardial perfusion scintigraphy (MPS) is based on retrospective studies with controversial results. Moreover, the true incidence of obstructive coronary artery disease (CAD) in these patients is unknown.     

Delayed presentation of vernix caseosa peritonitis

INTRODUCTION

Vernix caseosa peritonitis (VCP) is a rare and poorly recognised condition resulting from a sustained foreign body reaction to the vernix caseosa of the baby. This case-based review aims to highlight its importance for any medical team managing patients with peritonitis who have undergone a recent Caesarean section.

CASE REPORT

A 31-year-old woman presented 5 weeks after a Caesarean section with symptoms and signs of peritonitis.

CONCLUSIONS

Laparotomy and peritoneal lavage is the mainstay of treatment for VCP. Knowledge of the condition may stop inadvertent resection of normal intra-abdominal organs. Greater awareness of VCP is required to ensure earlier recognition as patients can recover well following timely operative intervention.     

IADL functions, cognitive deficits, and severity of depression: a preliminary study.

OBJECTIVE: Despite the documented association of cognitive dysfunction with impairment in instrumental activities of daily living (IADLs) in geriatric depression, the relationship among deficits in distinct IADLs with severity of depression and specific cognitive impairments remains to be clarified. The authors examined the relationship of depression severity and the cognitive domains of attention, initiation/perseveration, construction, conceptualization, and memory to nine distinct IADLs. METHODS: The subjects were 105 nondemented elderly patients but with impairment in at least one IADL and a history or presence of major depression. Impairment in IADLs and severity of depression were assessed with the Philadelphia Multilevel Assessment Instrument (MAI) and the 24-item Hamilton Depression Rating Scale (Ham-D), respectively. Cognitive dysfunction was assessed with the Mini-Mental State Exam (MMSE) and the Mattis Dementia Rating Scale (DRS). RESULTS: Six IADLs were influenced by impairment in at least one of the cognitive domains. Abnormal scores in initiation/perseveration, an aspect of executive dysfunction, was the cognitive impairment affecting most IADLs; it interfered with the ability to shop for groceries, prepare meals, take medicine, and manage money. Impairment in initiation/perseveration had a most prominent effect in the presence of depressive symptoms and affected shopping for groceries and preparing meals. Lack of interest and motivation, part of the depressive syndrome, compounded by behavioral abnormalities resulting from executive dysfunction, may account for this interaction. CONCLUSIONS: These relationships may provide the background for developing interventions targeting functional deficits associated with specific cognitive dysfunctions and depression.