A comparison of the long-term effects of sotalol and atenolol on QT interval and arrhythmias after myocardial infarction

In order to dissociate the Class III effects of sotalol on QT interval and arrhythmias from those of chronic beta-receptor blockade, we compared the effects of sotalol 160 mg b.d. and atenolol 50 mg b.d. in a double-blind crossover study of 103 patients followed for one year after discharge following acute myocardial infarction. Sotalol caused a highly significant lengthening of the absolute and corrected QT (QTc) interval over atenolol which was apparent by day 6 and persisted unchanged throughout the follow-up period. The increase in QT interval averaged 43 ms (9%). Sotalol blunted the increase in ventricular premature beat frequency on ambulatory monitoring which occurred with atenolol, although direct comparison of arrhythmia frequency between the groups receiving atenolol and sotalol revealed no significant difference. Marked lengthening of QTc interval (greater than 500 ms) was observed on 29 occasions in patients receiving sotalol, most commonly at day 6, but no episodes of polymorphic ventricular tachycardia were recorded. The Class III action of sotalol persists over and above any response to beta-blockade during a one-year follow-up period. In a population with a low incidence of spontaneous arrhythmias, however, there was only a modest difference in antiarrhythmic efficacy between atenolol and sotalol. Episodes of marked lengthening of QT interval induced by sotalol in the absence of other adverse factors need not be arrhythmogenic.     

Significance of serum bilirubin level in response of hepatocellular carcinoma to doxorubicin

To determine which of several clinical and laboratory features could be of significance in the response of hepatocellular carcinoma to doxorubicin we have analysed the frequency of remission in 143 patients treated with this drug. Of those features investigated including age, sex, presence and aetiology of underlying cirrhosis, duration of symptoms, performance grade and liver function tests, a normal serum bilirubin level was shown to be the only one on logistic regression analysis to predict a greater change of response (response rate = 46% with serum bilirubin less than 20 mumol/l and 10% with bilirubin greater than 20 mumol/l). The most likely explanation is that reduction in doxorubicin dosage according to the serum bilirubin level, based on the view that the risk of myelosuppression is thereby lessened, may lead to suboptimal dose administration.     

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.     

Afternoon nap, meal ingestion and circadian variation of acute myocardial infarction

A two-peaked circadian variation in acute myocardial infarction has been demonstrated, with a morning peak attributed to physiological changes produced by nocturnal sleep. To investigate the causes of the secondary peak, we compared meal habits and circadian variation in patients with acute myocardial infarction who were accustomed to afternoon naps (group A) to those who were not (group B). One hundred and fifty two patients formed group A and 65 group B. The main meal was lunch in group A (77%) and dinner in group B (74%). Both groups displayed a significant circadian variation, (group A: x2=51.3, group B: x2=60.4, both p < 0.0001), but the secondary peak occurred earlier (2pm-4pm) in group A, than in group B (6pm-8pm). We conclude that ingestion of the main daily meal, followed by a period of physical inactivity, with or without sleep, is a trigger for acute myocardial infarction.     

Genetic variants of WNK4 in whites and African Americans with hypertension

Human chromosome 17q has been implicated to contain a gene that influences hypertension susceptibility. This region contains the WNK4 gene that causes the mendelian disorder pseudohypoaldosteronism type II, characterized by high potassium levels and hypertension. The goal of this study was to identify genetic variants in all exons of WNK4 in hypertensive individuals and to examine the association of these variants with essential hypertension. Single-nucleotide polymorphims (SNPs) were identified by sequencing the entire coding region in 32 whites and 32 African Americans with hypertension. A single SNP in whites and 8 SNPs in African Americans were genotyped in a larger cohort of whites (165 hypertensives; 91 normotensives) and African Americans (120 hypertensives; 98 normotensives). The frequency of the rare allele differed significantly between hypertensive whites (13.0%) and normotensive whites (7.1%, P=0.040) for the single intronic SNP (bp 1 156 666). This difference remained significant after adjusting for body mass index and sex (P=0.035). Genotypic frequencies differed significantly between hypertensive and normotensive individuals when a dominant model either with (P=0.027) or without (P=0.028) covariate adjustment was assumed. The odds ratio for hypertension was 2.28 for AA or AG individuals vs those with the GG genotype (95% confidence interval, 1.09 to 4.75). No significant differences in allelic or genotypic frequencies were observed in African Americans for any SNPs. The finding in whites is consistent with the hypothesis that polymorphisms in WNK4 influence the risk of hypertension. However, because the associated SNP does not appear to be a functional variant and the limitations of case/control association studies, confirmation of these results in additional cohorts is warranted.     

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.