Candida prosthetic valve endocarditis cured by caspofungin therapy without valve replacement.

A 64-year-old woman with a mechanical mitral valve prosthesis developed late-onset Candida endocarditis. Blood cultures grew Candida glabrata and Candida krusei. Transesophageal echocardiography demonstrated vegetations on the valve. The patient was not medically fit for valve replacement, but her condition was successfully treated with 6 weeks of intravenous caspofungin therapy.

Metabolic modulation of cardiac neurosympathetic activity in vivo: effects of potassium and adenosine.

The effects of intracoronary (LAD) infusion of potassium and adenosine on changes in coronary vascular resistance and regional cardiac noradrenaline overflow during graded cardiac sympathetic stimulation were assessed in non-ischaemic myocardium in the open chest anaesthetised dog. Intracoronary potassium at three concentration (10, 25, 75 mmol.litre-1) progressively increased the potassium content of local venous effluent from 3.6 to 9.4 mmol.litre-1 and produced biphasic effects on nerve stimulated regional noradrenaline overflow. At low dose it was inhibitory (peak overflow at 20 Hz stimulation being reduced from (mean(SEM)) 10.2(2.6) to 2.9(1.8) pmol.ml-1 with 10 mmol.litre-1 potassium chloride; p less than 0.01). At high dose, overflow was potentiated to 13.3(2.7) pmol.ml-1 with 75 mmol.litre-1 potassium chloride (p less than 0.05). Noradrenaline overflow from and the potassium content of circumflex territory venous effluent was unchanged. Intracoronary adenosine at high concentration (10(-3) and 10(-2) mol.litre-1) potentiated basal noradrenaline overflow from the heart producing a small negative arteriovenous concentration difference of 0.6(0.7) and 1.0(0.6) pmol.ml-1 respectively. However, noradrenaline overflow during maximal sympathetic stimulation was inhibited from 3.8(1.4) to 0.4(0.7) pmol.ml-1 with 10(-3) mol.litre-1 adenosine and to 0.7(0.6) pmol.ml-1 with 10(-2) mol.litre-1 adenosine (p less than 0.05). The changes in blood flow and coronary vascular resistance seen with sympathetic stimulation were not modified by adenosine, despite major alteration in basal coronary vascular tone. Thus both metabolites may potentially alter local neurosympathetic activity in ischaemic myocardium and act diversely to determine noradrenaline release at the nerve terminal.

Relationship of neurosympathetic responsiveness to early ventricular arrhythmias in ischaemic myocardium.

Myocardial catecholamine overflow has been measured in open-chest anaesthetised dogs after graded stimulation of the left ansa subclavia before and during left anterior descending coronary artery occlusion and on reperfusion. Sequential 1 min periods of ansa stimulation over 3 h resulted in reproducible, frequency dependent regional myocardial noradrenaline (NA) overflow without tachyphylaxis. In seven dogs, two successive 10 min periods of LAD occlusion did not modify peak myocardial NA overflow from the predominantly ischaemic (I) or non-ischaemic (NI) areas at either low (1 Hz) or high (10 Hz) frequency ansa stimulation. In a second group of nine dogs, myocardial catecholamine overflow was related to changes in ischaemic area epicardial activation delay during repeated ansa stimulation on four occasions during 75 min of ischaemia. Stimulation at the period of peak spontaneous arrhythmias 5 and 17 min after coronary occlusion resulted in NA overflow from I of 2.8 +/- 1.3 and 3.0 +/- 1.6 pmol X ml-1 respectively and a significant increase in mean activation delay in I of 12 +/- 4 ms at 5 min and 9 +/- 4 ms at 17 min (p less than 0.05). In contrast, stimulation 30 and 60 min after coronary occlusion, when spontaneous arrhythmias are rare, was not associated with NA overflow from ischaemic areas (0.3 +/- 0.3 and 0.9 +/- 0.5 pmol X ml-1 respectively) and resulted in a minor reduction in mean activation delay in ischaemic areas of 2 +/- 3 ms at 30 min and 3 +/- 4 ms at 60 min. NA overflow from non-ischaemic areas and increases in blood pressure and myocardial lactate release were similar during each period of ansa stimulation. Coronary reperfusion induced massive overflow of NA (11.4 +/- 2.8 pmol X ml-1) and reduced extraction of adrenaline (A) from ischaemic areas with a time course similar to early reperfusion arrhythmias. Stimulation-evoked release of NA in ischaemic myocardium is thus maintained during the early period of enhanced vulnerability to arrhythmias and during reperfusion but is inhibited after 30 min. This temporal variability may be a factor in the time course of spontaneous arrhythmias in this model.

Neuroendocrine activation in congestive heart failure.

Several changes in neuroendocrine activity follow failure of cardiac function to satisfy peripheral requirements and contribute to the clinical syndromes of heart failure. Afferent pathways are poorly understood and triggers are both central and peripheral, involving attenuation of atrial and arterial baroreceptor activity. Efferent sympathetic activity is generally increased with resulting vasoconstriction, but responses are organ-specific and differ among heart, kidney, lung and skeletal muscle. Changes in cardiac sympathetic activity are inadequately understood. Enhanced cardiac norepinephrine spillover contrasts with reduced tissue concentration and impaired activity of synthetic enzymes and neuronal catecholamine uptake. Beta-receptor down-regulation further complicates overall adrenergic responsiveness and the balance between enhancement of contractile function and reduction in arrhythmia threshold. Activation of the renin-angiotensin system is potentiated by the sympathetic nervous system and may contribute to vasoconstrictor hyporesponsiveness. Angiotensin II may in turn facilitate the central and peripheral effects of sympathetic activation and the release of vasopressin from the pituitary. Our understanding of the role of vasodilator peptides in heart failure remains rudimentary. It is likely that vasoconstrictor neuroendocrine response adversely influences optimal cardiac function in heart failure and may promote arrhythmogenesis. The neuroendocrine response in individual organs, however, requires intensive study.

Occult thyrotoxicosis: a correctable cause of "idiopathic" atrial fibrillation.

Serum total thyroxine, triiodothyronine and thyrotropin response to thyrotropin-releasing hormone were measured in 75 consecutive patients presenting to a cardiology clinic with atrial fibrillation with no obvious cardiovascular cause. A lack of response of serum thyrotropin to thyrotropin-releasing hormone, indicative of thyrotoxicosis, was found in 10 patients (13 percent), not all whom had raised serum thyroid hormone levels. These 10 patients were predominantly male, had no clinical signs of thyrotoxicosis and a relative excess of nonpalpable autonomous thyroid nodules demonstrated with scintigraphy. Eight of the 10 patients had reversion to stable sinus rhythm after treatment with iodine-131 or carbimazole, either spontaneously or after direct current cardioversion. It would appear that clinically occult thyrotoxicosis can be identified consistently only with the thyrotropin-releasing hormone test and is the cause of "idiopathic" atrial fibrillation in a significant proportion of patients.

Reoperation for prosthetic valve endocarditis in the third trimester of pregnancy.

A pregnant 29-year-old woman underwent emergency aortic valve re-replacement for prosthetic valve endocarditis. Cesarean section was performed with the chest open ready for cannulation. Fears of uterine hemorrhage during systemic heparinization for cardiopulmonary bypass were unfounded, and both mother and the 28-week-gestation newborn recovered uneventfully.

Cardiac catheterisation performed by a clinical nurse specialist.

OBJECTIVE: To establish the feasibility and safety of an appropriately trained clinical nurse specialist performing diagnostic cardiac catheterisation. DESIGN: Non-randomised retrospective comparison between the first 100 and second 100 consecutive investigations by a clinical nurse specialist and 200 consecutive patients investigated by two cardiology registrars over a similar period. SETTING: Regional cardiac centre performing 3200 catheterisation procedures per annum. PATIENTS: 200 patients undergoing routine (non-emergency) cardiac catheterisation for investigation of ischaemic heart disease. MAIN OUTCOME MEASURES: Procedural complications, image quality, fluoroscopy times. RESULTS: Satisfactory diagnostic images in all nurse specialist cases with no deaths and two complications (coronary artery dissection and femoral pseudoaneurysm). Procedure duration and fluoroscopy times slightly shorter for clinical nurse specialist by 3 and 1.6 minutes, respectively (P < 0.05). CONCLUSIONS: Non-medical practitioners can be trained to perform straightforward cardiac angiography in low risk patients with consultant supervision, as for cardiology registrars. With important restrictions such posts may have a limited role in supporting future consultant based services.

Plasma noradrenaline as an index of sympathetic tone in coronary arterial disease: the confounding influence of clearance of noradrenaline.

Kinetics of [3H]noradrenaline in the plasma were compared with plasma noradrenaline concentration in assessing overall sympathetic activity in six groups totalling 118 subjects. Arterial plasma noradrenaline in 21 control subjects was 204 +/- 14 pg/ml, similar to 20 patients with stable angina not treated with beta-blockers (194 +/- 25 pg/ml) and to 31 patients with stable angina treated with beta-blockers (232 +/- 19 pg/ml). Plasma noradrenaline was increased in 17 patients with unstable angina (366 +/- 50 pg/ml, P less than 0.01), in 14 patients with recent acute myocardial infarction (460 +/- 44 pg/ml, P less than 0.001) and in 15 patients with treated cardiac failure (582 +/- 78 pg/ml, P less than 0.001). Whole body clearance of noradrenaline from plasma was, however, reduced in each of the last three groups compared to controls by 20% (P less than 0.05), by 34% (P less than 0.01) and by 31% (P less than 0.01), respectively. In the 31 patients with stable angina on beta-blockers, clearance of noradrenaline was also reduced by 20% (P less than 0.05). Whole body noradrenaline spillover, a potentially more accurate measure of overall sympathetic activity than concentration of noradrenaline in plasma, was 235 +/- 20 ng min-1 m-2 in controls, was similar in subjects with stable angina (no beta-blockers; 260 +/- 34 ng min-1 m-2, beta-blockers; 200 +/- 17 ng min-1 m-2), but was increased in patients with unstable angina (310 +/- 27 ng min-1 m-2, P less than 0.05), with recent acute myocardial infarction (346 +/- 40 ng min-1 m-2, P less than 0.05) or with heart failure (438 +/- 65 ng min-1 m-2, P less than 0.01). Overall sympathetic activity is unchanged in stable angina, but is progressively increased in patients with unstable angina, recent myocardial infarction or heart failure. Plasma concentration of noradrenaline fails accurately to reflect this as a result of decreased clearance of noradrenaline in these patients. The results show the potential limitations of measurement of noradrenaline in the plasma as an index of overall sympathetic activity and the importance of assessing clearance.

Coronary venous noradrenaline during coronary angioplasty.

Coronary venous and arterial noradrenaline concentrations were measured during percutaneous transluminal coronary angioplasty in 14 patients. Coronary venous noradrenaline did not increase significantly during balloon inflation but was increased during early reperfusion in patients undergoing left anterior descending angioplasty (n = 8), from 157 +/- 38 pg/ml to 295 +/- 94 pg/ml (P less than 0.05). Coronary blood flow, measured by thermodilution in 7 further patients during left anterior descending angioplasty, was 69 +/- 9 ml/min, decreased to 80 +/- 3% of basal flow during balloon inflation (P less than 0.01) and increased to 135 +/- 5% during early reperfusion (P less than 0.01). It was estimated using these results that cardiac spillover of noradrenaline did not change during occlusion of the left anterior descending artery, but increased almost 3-fold during early reperfusion. During the period of balloon inflations, there was a modest increase in overall sympathetic tone, as assessed by total noradrenaline spillover to plasma (400 +/- 77 ng/min to 473 +/- 87 ng/min, P less than 0.01). These results, suggesting an increase in release of noradrenaline during early reperfusion following brief occlusion of the left anterior descending artery, may be relevant to the genesis of reperfusion arrhythmias.

Atrial fibrillation and isolated suppression of the pituitary-thyroid axis: response to specific antithyroid therapy.

Four patients are described with persistent atrial fibrillation associated with normal plasma total thyroxine (T4) and triiodothyronine (T3) but an absent plasma thyrotrophin (TSH) response to intravenous thyrotrophin releasing hormone (TRH). Initial cardioversion failed to establish sinus rhythm in three of the four patients. Following specific antithyroid therapy to lower thyroid hormone levels sufficient to allow a normal TSH response to TRH sinus rhythm was established in all four patients, one spontaneously and three after cardioversion. Stable sinus rhythm has persisted in three patients over a 2-yr follow-up period. In the presence of atrial fibrillation, an absent plasma TSH response to TRH should be considered sufficient grounds for antithyroid therapy even if plasma total T4 and T3 are within the expected normal range.

Recurrent Listeria monocytogenes meningitis in a heart transplant recipient.

A case of recurrent Listeria monocytogenes meningitis is reported, the two episodes arising 4 months and 8 months after the patient had received a heart transplant. Both episodes immediately followed increased doses of corticosteroids for allograft rejection. The source of infection was not identified. Previous reports and possible explanations of recurrent L. monocytogenes infection are reviewed.

Long-term outcomes of percutaneous coronary intervention for unprotected left main coronary artery disease.

BACKGROUND: This study evaluates the in-hospital, 30 day and long-term results of stenting for unprotected left main coronary artery disease in our institution. METHODS: Between April 2001 and October 2005 all unprotected left main cases were retrospectively reviewed. Outcomes were obtained by case note review and postal questionnaire; primary care physicians were contacted to complete missing data. RESULTS: We identified 100 consecutive patients who underwent unprotected left main procedures, 1.44% of the institution PCI volume. Indications for a percutaneous strategy were non-surgical candidates (47), emergency revascularisation (25) and patient/physician preference (28). Overall procedural success was 97%. The majority of cases (n=78) were performed with a single-stent strategy. 55% received a drug-eluting stent. There were 7 in-hospital deaths, 5 in the emergency group (cardiogenic shock) and 2 non-CABG candidates. Post hospital discharge long-term clinical follow-up was 651+/-431 days (range 6-1741). There were 8 deaths post discharge. Patients presenting as an emergency had a 72% survival rate at long-term follow-up, non-surgical candidates 83%, and patient/physician preference group had a 100% long-term survival. Multivariate analysis revealed cardiogenic shock (HR=7.9, 95% CI 1.7-3.6, p=0.008), failed thrombolysis (HR=8.5, 95% CI 1.7-41.7, p=0.008) and use of a bare-metal stent (HR=4.4, 1.1-17.0, p=0.034) were independent predictors of mortality. CONCLUSIONS: Our data suggest that in contemporary practice stenting for unprotected left main disease can be considered as an alternative treatment to surgery for selected patients. The results of randomised controlled trials are awaited.

Ectopic ACTH syndrome from bronchogenic carcinoma in association with chronic lymphocytic leukaemia.

A patient under treatment for chronic lymphocytic leukaemia developed lobar pneumonia after 8 months. When antileukaemic therapy was discontinued, features of an ectopic ACTH syndrome developed, secondary to bronchogenic carcinoma. Exogenous steroid therapy for leukaemia seemed to suppress the clinical manifestations of the ectopic ACTH syndrome while subsequent endogenous steroid production controlled the peripheral lymphocyte count.

Selective enhancement of the cardiac sympathetic response to exercise by anginal chest pain in humans.

Cardiac and whole body [3H]norepinephrine kinetics were used to evaluate the response of overall and cardiac sympathetic activity to supine bicycle exercise in 31 patients with coronary artery disease (CAD) and in nine normal control subjects (group 1). Of the 31 patients with CAD, 20 developed evidence of myocardial ischemia during exercise (group 2), typical angina occurring in 20 of 20 and ischemic ST segment changes in 13 of 20, whereas 11 patients developed no evidence of ischemia (no chest pain or electrocardiographic changes) (group 3). Exercise resulted in increased total and cardiac NE spillover in all groups of patients. Basal cardiac NE spillover was similar in the three groups (group 1, 5 +/- 1 ng/min; group 2, 8 +/- 1 ng/min; group 3, 7 +/- 2 ng/min; p = NS), but during exercise, cardiac NE spillover was greater in patients who developed angina (group 2, 30 +/- 5 ng/min) than in those who did not (group 1, 17 +/- 2 ng/min; group 3, 17 +/- 2 ng/min; p less than 0.05). The increases in total NE spillover were similar in the three groups. Supine bicycle exercise increases cardiac and overall sympathetic tone in normal control subjects and in patients with CAD. The occurrence of angina selectively enhances the cardiac sympathetic response to exercise. In the absence of angina, patients with CAD and control subjects without CAD have similar sympathetic responses to exercise.

Plasma [3H]noradrenaline kinetics in man: is separation of alumina extracts by high performance liquid chromatography necessary?

1. After an 80 min intravenous infusion of 1-[3H]noradrenaline ([3H]NA) in 19 subjects, the proportion of alumina-extractable 3H due to [3H]NA was 86 +/- 2% in arterial and 78 +/- 2% in venous plasma. [3H]Dihydroxy-phenylethyleneglycol ([3H]DHPG) accounted for 8 +/- 1% in arterial and 13 +/- 1% in venous plasma. [3H]Dihydroxymandelic acid ([3H]DOMA) was not detected. 2. No time-dependent change in the proportion of alumina-extractable 3H due to [3H]NA was seen in either arterial or venous plasma over this period. In venous plasma the proportion of alumina-extractable 3H due to [3H]DHPG increased slightly between 30 and 80 min, from 10 +/- 1% to 13 +/- 1%. 3. The results were unchanged with chronic beta-blockade and with either 1-[2,5,6-3H]NA or 1-[7,8-3H]NA. 4. After [3H]NA infusion in man the radioactivity recovered after alumina extraction is predominantly [3H]NA and thus can be used directly to determine [3H]NA kinetics without the need for metabolite separation.

Cardiac and whole body [3H]noradrenaline kinetics in ischaemic heart disease: contrast between unstable anginal syndromes and pacing induced ischaemia.

Radiotracer kinetics were used to evaluate the activity of the sympathetic nervous system in 10 patients who had had unstable ischaemic symptoms within the previous 12 weeks and 10 with stable angina. Patients with recent unstable angina or angina after recent acute myocardial infarction had higher basal cardiac noradrenaline spillover than patients with stable angina. This represents a selective increase in cardiac sympathetic tone because whole body noradrenaline spillover was not significantly increased in the patients with recent unstable angina. Atrial pacing in 15 patients caused angina in 13 but did not significantly alter cardiac noradrenaline spillover in either patients with stable or unstable angina. The flow of plasma in the coronary sinus increased during pacing but because cardiac noradrenaline extraction decreased cardiac noradrenaline clearance was not significantly altered. Both whole body noradrenaline spillover and clearance were modestly increased by pacing, and arterial noradrenaline concentration was unchanged. Patients with recent symptoms of unstable ischaemia had a sustained and selective increase in cardiac efferent sympathetic tone compared with patients with stable angina, and angina induced by atrial pacing did not cause important cardiac sympathetic activation.