What is the effect of penicillin dosing interval on outcomes in streptococcal infective endocarditis?

OBJECTIVES: Penicillin is an important treatment option for streptococcal infective endocarditis (IE), but its short half-life requires frequent re-dosing (4- or 6-hourly). There is a variation between the dosing regimens in different guidelines and consequent differences in the dosing interval. The objective of this study was to examine the relationship between the penicillin dosing interval and outcomes in streptococcal IE. METHODS: A retrospective study of cases of streptococcal IE was undertaken using the Leeds Endocarditis Service database. Cases were included if the first-line therapy had been penicillin and excluded if patients had received less than 72 h of therapy. Details of antimicrobial therapy and outcomes were collated using strict definitions. Various parameters were considered as independent variables in a multivariate logistic regression analysis. Univariate analysis of categorical data was carried out using a χ(2) test, and analysis of continuous data using an unpaired t-test. RESULTS: Two hundred and twelve cases were included in the final analysis. Of the parameters considered, a 4-hourly dosing interval [unadjusted OR = 2.79 (95% CI 1.43-5.62)] and initial echocardiographic evidence of abscess or severe valve regurgitation [unadjusted OR = 0.30 (95% CI 0.13-0.66)] were the only statistically significant factors associated with the success or failure of penicillin therapy. The odds of a successful outcome were almost three times greater with a 4-hourly regimen than with a 6-hourly regimen. Failure of penicillin therapy had no correlation with the MIC of penicillin or the concurrent administration of gentamicin. CONCLUSIONS: Penicillin continues to be an effective therapy for IE. This study suggests that a 4-hourly dosing interval may be relevant in predicting the success of initial medical therapy. Further prospective studies are warranted to evaluate relationships in more detail.

Treatment of hypertension induces a fall in platelet basal cytoplasmic calcium concentration without influencing platelet aggregation.

The relationship between blood pressure and platelet basal cytoplasmic calcium concentration ([Ca2+]i) and platelet sensitivity to aggregating agents in hypertension has been investigated in hypertensive patients and normotensive subjects. Ten severely hypertensive patients whose blood pressures were poorly controlled with metoprolol, were given calcium antagonist (either nifedipine or felodipine) as a second line agent. Venous blood samples were collected at each treatment phase for measurement, in whole blood, of platelet aggregation in response to ADP and collagen, and of basal [Ca2+]i using fura-2. Control of blood pressure by the combination of metroprolol and a calcium antagonist induced a significant decrease in median [Ca2+]i from 116 (76-181) to 73 (60-83) nM, which was similar to the median value of 70 (61-80) nM obtained in 14 normotensive subjects. Overall [Ca2+]i correlated with mean blood pressure (r = 0.51). Treatment of hypertension with calcium antagonist did not change the response of platelets to collagen or ADP. The results confirm that effective treatment of hypertension significantly reduced basal [Ca2+]i in platelets but raise doubts whether elevated basal [Ca2+]i is necessarily the sole mechanism by which the sensitivity of platelets to aggregatory agents is increased in hypertension.

Amiodarone-induced torsades de pointes: the possible facilitatory role of digoxin.

Poorly controlled supraventricular arrhythmias in a hypokalaemic 74 year old woman were treated with oral amiodarone. This caused torsades de pointes, and was preceded by marked prolongation of the QT interval. The induction of torsades de pointes by amiodarone is thought to be an idiosyncratic reaction to amiodarone itself which is facilitated by electrolytic abnormalities. The present case, however, indicates the possibility of a pro-arrhythmic effect secondary to an interaction between amiodarone and digoxin.

Can central neuropeptides be implicated in carotid sinus reflex hypersensitivity?

Carotid sinus reflex hypersensitivity involves profound and intermittent changes in heart rate and blood pressure associated with symptoms of dizziness and syncope. This involves a reflex arc in which the main defect is believed to lie within the central nervous system. The discovery of classical and peptidergic neurotransmitters within the same neurone, and the presence of these peptides within the central nervous system raises the possibility that carotid sinus reflex hypersensitivity may be related to an abnormality of peptide distribution or function.

Thyrotoxic periodic paralysis: an unusual presentation of weakness.

Thyrotoxic periodic paralysis is a rare endocrine disorder seen predominantly in men of Asian origin. The case is reported of a patient who presented to the accident and emergency department with sudden onset of weakness of his lower limbs. Hypokalaemia was identified and treated with resolution of symptoms. Additional tests identified the patient as being thyrotoxic. He was treated with oral antithyroid drugs. It is important to consider the diagnosis of thyrotoxic periodic paralysis in patients presenting with acute onset of weakness. The report discusses the epidemiology, presentation, treatment, and complications of this condition.

Pharmacologic perfusion imaging. Who needs it and why?

Pharmacologic perfusion imaging is an excellent choice for patients who cannot undergo treadmill exercise stress testing. The use of pharmacologic imaging has proved valuable in all branches of medicine and surgery. Patients requiring cardiac evaluation before vascular or orthopedic surgery can now be examined quite completely; there are very few patients today who cannot be "stressed" adequately. Advances in this field are being made every day, and the accuracy of testing will improve further when such new technologies as positron-emission tomography are more widely available.

Late-onset prosthetic valve endocarditis caused by Mycoplasma hominis, diagnosed using broad-range bacterial PCR.

We report what is believed to be the first case of late-onset prosthetic valve endocarditis caused by Mycoplasma hominis in a case of blood culture-negative endocarditis. The objective of this report is to emphasize the use of a broad-range PCR technique for bacterial 16S rRNA genes in identifying the causative pathogen, thus enabling targeted antimicrobial treatment.

Comparison of unipolar and bipolar ventricular paced evoked responses.

OBJECTIVES: To study the differences between endocardial bipolar and unipolar ventricular paced evoked responses and surface electrocardiograms. PATIENTS: 10 patients with conduction system disease awaiting insertion of a permanent pacemaker were studied with temporary ventricular pacing from the right ventricular apex. MAIN OUTCOME MEASURE: Comparison of the durations of the QRS complexes and QTa and QTe intervals of the endocardial bipolar paced evoked response and the surface electrocardiogram with those of the reference unipolar paced evoked response. RESULTS: By comparison with the unipolar reference, the mean durations of the QRS complexes of the bipolar signal and the surface electrocardiogram were 41.8% and 132.1% respectively. The mean QTa interval was 85.9% and 112.2% respectively and the mean QTe interval was 86.9% and 109.5% respectively. All these differences were significant. The amplitudes of the unipolar QRS complexes and T waves were significantly larger than those recorded in the bipolar configuration. CONCLUSIONS: Differences between the unipolar and bipolar ventricular paced evoked responses are significant. The time course of the unipolar signal is closer to that of the surface electrocardiogram. This indicates that the unipolar paced evoked response does not reflect local electrophysiological events, as has been suggested previously.

One-year follow-up of automatic adaptation of the rate response algorithm of the QT sensing, rate adaptive pacemaker.

Optimal functioning of a rate adaptive pacemaker depends upon reliable sensing of the sensor and appropriate programming of the rate of response algorithm. QT sensing pacemakers use data derived from the endocardial electrogram in the programming of the rate response algorithm. In the latest versions of these pacemakers, programming of the rate response algorithm may be performed using either a semiautomatic Fast Learn (FL) procedure or by using the newly developed, fully Automatic Slope Adaptation (ASA) mechanism. We report our experience in a prospective study of 17 patients in the first year postimplantation. ASA was characterized by significant changes only in the values of the slope settings at the lower rate limit (3.7 msec/msec at time 0 to 5.77 msec/msec at 2 weeks, P less than 0.001) during the first 2 weeks after its enablement. Further adaptation between weeks 2 to 4 was observed (5.77 msec/msec to 6.4 msec/msec, P = 0.2) but this was not significant. The slope settings derived using the FL procedure were also checked at 2 and 4 weeks and were reproducible. They were closest in value to the values attained by the automated mechanism at 4 weeks. This suggests that the final value of the slope setting at the lower rate limit using ASA is reached between weeks 2 to 4. Both methods of slope determination result in satisfactory and similar rate response profiles but the time to achieve slope stability will necessarily be slower with ASA.

The use of dobutamine stress thallium scintigraphy in the diagnosis of syndrome X.

Dobutamine stress thallium scintigraphy is a non-exercise stress technique used in the assessment of myocardial ischaemia. Non-exercise techniques are independent of the patient's exercise capacity or the subjective development of limiting symptoms. Preliminary data are presented regarding the effects of graded infusions of dobutamine (maximum 20 micrograms/kg/min) in seven consecutive patients with syndrome X. The dobutamine stress test caused significant increases in mean heart rate (rest 65.4 beats/min, peak dobutamine infusion 112.4 beats/min, P < 0.001) and systolic blood pressure (rest 138.6 mmHg, peak dobutamine infusion 166.7 mmHg, P = 0.002) and provoked typical symptoms in all the patients. Single photon emission computerized tomography was performed and the mean number of reversible defects was 1.86 per patient (range 1-3). One patient developed transient atrial fibrillation during the dobutamine infusion but there were no complications in the remainder of the study group. It is concluded that dobutamine-thallium scintigraphy in patients with syndrome X is safe, reproduces patients symptoms' reliably and presents a controllable degree of stress to the cardiovascular system. The consistent demonstration of a reversible perfusion defect in patients with syndrome X is evidence of abnormal myocardial physiology. This criterion could be added to those currently used to define syndrome X in order to improve objectively the identification of this patient group.

Nonlinear relationship between pacing and evoked QT intervals.

The paced evoked response is an established biosensor which has been used in the design of a rate responsive pacemaker. The unit is capable of sensing the interval between the delivery of a pacing stimulus and the downslope of the evoked T wave. With fixed rate pacing this interval has been shown to shorten with exercise and the main cause of this effect is thought to be mediated by the increase in the plasma catecholamines which are released on exertion. The detection of a reduction in the stimulus-T interval results in an increase in pacing rate. The rate of change of pacing rate is referred to as the slope setting and this must be determined for each individual patient so that optimal rate responsive pacing can be effected. The algorithm underlying the slope setting is the pacing rate-evoked QT interval relationship. This relationship was implemented as a linear function, but this study, which was conducted to reevaluate it, has demonstrated nonlinearity between the pacing and evoked QT intervals. The degree of QT shortening is least at low heart rates. This finding has resulted in the development of a new algorithm for the pacemaker in the form of a new program for the pacing system. This should result in a more physiological rate of change of heart rate with exercise and less chance of sudden changes in rate. These postulates are the subject of current clinical trials.

Improved pattern of rate responsiveness with dynamic slope setting for the QT sensing pacemaker.

We have recently described the electrophysiological basis of a new algorithm for the QT (TX) sensing rate responsive pacemaker. By using the new software program running on the standard programmer it has been possible to simulate the new algorithm in ten patients with complete heart block (seven patients had implanted TX units and three were paced with an external TX pacemaker) during routine exercise testing. In this way a single-blind, intra-patient comparison of the pattern of pacing rate change using both the existing and new algorithms was possible. In nine out of the ten cases the time taken to increase the pacing rate from 70 to 80 bpm was reduced significantly when the new algorithm was used (P = 0.037). Additionally, the correlation between the atrial and ventricular rates in those patients with normal sinus node function (seven patients) was determined. In all cases we have observed a significantly improved correlation between the atrial and ventricular paced rates during exercise with the new algorithm (P less than 0.001).

A randomized double-blind, cross-over study of the linear and nonlinear algorithms for the QT sensing rate adaptive pacemaker.

We have compared the pacing rate responses during cardiopulmonary exercise testing in 11 patients (mean 59 years, six female) with implanted QT sensing rate adaptive pacemakers who were randomly programmed to 1-month periods in the linear and nonlinear algorithms using a double-blind, cross-over design. Exercise testing was performed at the end of each month block and symptoms were scored with the MacMaster questionnaire. With exercise, the time to a 10 beats/min increment in rate was significantly less with the nonlinear compared to the linear algorithm (126 sec vs 255 sec, P = 0.02) but there were no significant differences in exercise duration, the peak pacing rate, the peak VO2, the VO2 at the anaerobic threshold or the mean correlation coefficients of the pacing rate VO2 relationship. Rate oscillation occurred in seven patients in the linear algorithm and in two patients in the nonlinear setting. Initial deceleration of the pacing rate at the onset of exercise occurred in seven patients in the linear algorithm and in four patients in the nonlinear setting. The nonlinear algorithm is associated with a faster response time during exercise and fewer instances of rate instability. However, it has not overcome the problem of a dip in the pacing rate at the beginning of exercise. The major difference in the function of the two algorithms is faster initial acceleration with the nonlinear algorithm. This is explained by the significantly higher values of the slope setting at the lower rate limit for the nonlinear versus the linear algorithm (6.3 ms/ms vs 5.1 ms/ms).

Coronary artery calibre after direct intra-arterial infusion of epoprostenol (prostacyclin).

Because epoprostenol (prostacyclin) is a prostaglandin that causes vasodilatation and inhibits platelet function it may be of benefit during coronary artery angioplasty. The safety and capacity of intracoronary epoprostenol to dilate coronary arteries were assessed in 16 patients undergoing routine coronary angiography. The view that best displayed the left epicardial coronary arteries was selected as a control for each patient. Intracoronary epoprostenol was then given and the angiogram was repeated in the chosen view. The procedure was repeated twice: once with a higher dose of epoprostenol and once after intracoronary isosorbide dinitrate. Angiograms were coded and analysed by an observer who was unaware of the treatment. The calibre of the arteries was measured from traced projections of the angiograms. The blood pressure, heart rate, and electrocardiogram were recorded throughout. The first two patients were given epoprostenol infusions of 2.5 and 5.0 ng/kg per minute to assess safety, and there were no untoward reactions. The next ten patients had epoprostenol infusions of 5.0 and 7.5 ng/kg per minute followed by intracoronary isosorbide dinitrate. No haemodynamic disturbances occurred and coronary luminal calibre did not change with epoprostenol (mean (SD) luminal diameter: 2.85 (0.62) mm control, 2.80 (0.61) mm at 5.0 ng/kg, and 2.80 (0.54) mm at 7.5 ng/kg), but it did increase significantly with isosorbide dinitrate (to 3.17 (0.36) mm). The last four patients had epoprostenol infusions of 7.5 and 10 ng/kg followed by intracoronary isosorbide dinitrate and two of them became hypotensive (one after epoprostenol and one after isosorbide dinitrate). Coronary luminal calibre did not change significantly (3.5 (0.45) mm control, 2.96 (0.81) mm at 7.5 ng/kg, 3.45 (0.96) mm at 10 ng/kg, and 3.20 (0.61) mm with isosorbide dinitrate). Eight patients developed tall T waves on the electrocardiogram during epoprostenol infusion but none had arrhythmias. The results indicate that clinically tolerable doses of intracoronary epoprostenol do not significantly dilate the epicardial coronary arteries. This route of administration is therefore unlikely to be of use during coronary angioplasty, although the antiplatelet action of intravenous epoprostenol might help to prevent restenosis.