A prospective randomized controlled trial of point-of-care testing on the coronary care unit.

BACKGROUND: We report the results of a prospective randomized controlled trial comparing point-of-care testing (POCT) with central laboratory testing (CLT) in a six-bed coronary care unit in a district general hospital. METHODS: 263 consecutive admissions with chest pain and suspected acute coronary syndrome were randomized to measurement of cardiac troponin T by POCT or CLT only. Patient management was according to a pre-specified protocol utilizing clinical features, electrocardiographic changes and cardiac biomarkers (creatine kinase and cardiac troponin T) to define management. Outcome measures were diagnostic accuracy compared with CLT as 'gold standard', result turnaround time, mortality and length of stay in all patients and those with a protocol-driven early discharge policy. RESULTS: Diagnostic accuracy and mortality was equivalent in the POCT and CLT arm. Overall there was no difference in length of stay. In the pre-specified early discharge group (n = 64) there was a significant reduction in median length of non-coronary care unit stay (145.3 h versus 79.5 h) and overall hospital stay (209.3 h versus 149.9 h) in those randomized to POCT. CONCLUSION: A combination of rapid biochemical diagnosis and structured decision making reduces length of hospital stay.

Impact of European Society of Cardiology/American College of Cardiology guidelines on diagnostic classification of patients with suspected acute coronary syndromes.

BACKGROUND: Assessment of the relative diagnostic accuracy of investigation strategies for patients with suspected acute coronary syndromes (ACS). METHODS: A prospective observational study followed two groups of patients over a 3-month period in a UK district general hospital. Group one: all admissions with suspected ACS (n = 576); group two: non-cardiac in-patients who were suspected of developing ACS (n = 87). Both were investigated by full clinical history, examination and serial electrocardiographs (ECGs). Conventional World Health Organization (WHO) criteria for myocardial damage were compared with diagnosis based on cardiac troponin T (cTnT). Clinical discharge diagnosis based on conventional WHO criteria was compared with the review diagnosis based on measurement of cTnT. RESULTS: Diagnosis based on WHO criteria missed 58 patients (8.7%) admitted with suspected ACS who had high risk unstable angina. Thirty-three patients (5% of all admissions) who were diagnosed as non-Q wave acute myocardial infarction (AMI) were found to have normal troponin values and to have been incorrectly classified as AMI. CONCLUSIONS: Diagnostic strategies based on WHO criteria are inaccurate. The measurement of cTnT in all patients with suspected ACS would have increased the number of those with a diagnosis of AMI by 58 (8.7%), while avoiding inaccurate diagnosis in 33 (5%), therefore producing an absolute increase of 25/663 (3.8%) but a relative increase of 58/138 (42%). In patients with a primary diagnosis of suspected ACS, the overall increase in patients with a diagnosis of AMI will be 55 (9.5%), a relative increase of 55/118 (46.6%) but an absolute increase of 36/576 (6.3%).

Troponin T measurement after myocardial infarction can identify left ventricular ejection of less than 40%.

AIM: To determine whether measurement of serum troponin T concentration after first acute myocardial infarction can be used to identify patients with a left ventricular ejection fraction of < 40%, who have an adverse prognosis. METHODS: Troponin T concentration was measured, and coronary and left ventriculography performed in 50 consecutive patients with acute myocardial infarction. Angiographic left ventricular ejection fraction was compared with serum troponin T concentration. Patients with previous myocardial infarction were excluded. RESULTS: There was a strong negative correlation between left ventricular ejection fraction and troponin T concentration. Spearman's rank correlation coefficient (corrected for ties) was -0.72 (95% confidence intervals (CI) -0.55 to -0.83; p < 0.0001). Analysis by receiver operator characteristic curve produced an area under the curve of 0.9773 (95% CI 0.9409 to 1.0136). A troponin T concentration of > 2.8 micrograms/l predicted a left ventricular ejection fraction of < 40% with a sensitivity of 100% (CI 84.6 to 100.0) and specificity of 92.9% (CI 76.5 to 99.1). Exclusion of patients who did not receive thrombolytic treatment did not significantly affect the results. CONCLUSION: Serum troponin T concentration measured 12-48 hours after admission for first myocardial infarction is a reliable, simple, quick, inexpensive, non-invasive method for identifying patients with a left ventricular ejection fraction of < 40% for whom there is a poor prognosis.

Direct current cardioversion does not cause cardiac damage: evidence from cardiac troponin T estimation.

AIM: To determine whether elective direct current (dc) cardioversion of atrial fibrillation/flutter causes myocardial damage. METHODS AND RESULTS: Cardiac troponin T and creatine kinase were estimated 20-28 hours after dc cardioversion in 51 patients who received dc shocks for elective cardioversion of chronic atrial fibrillation/flutter. Although creatine kinase was raised in 44 patients, cardiac troponin T was undetectable in all patients. CONCLUSION: Cardiac damage does not occur as a result of cardioversion.

Rapid troponin T measurement in whole blood for detection of myocardial damage.

A dry chemistry system for rapid qualitative measurement of cardiac troponin T in whole blood, serum, EDTA and lithium heparin plasma was studied in 197 admissions to the coronary care unit and general wards of a typical district general hospital for whom troponin T was requested. This included patients with unexplained collapse, acute dysrythmia or elevated creatine kinase of unknown origin. EDTA whole blood and plasma proved the most satisfactory sample matrices. Lithium heparin whole blood was equally appropriate but lithium heparin plasma gave a false negative result. Serum was an unsatisfactory sample material. Comparison with the conventional wet chemistry quantitative enzyme-linked immunosorbent assay showed a positive bias for EDTA plasma, particularly in the range 0-1 microgram/L and a significant negative bias for lithium heparin plasma. There was no difference between serum from plain or gel separator tubes. The whole blood method allows troponin T measurement to be performed rapidly and simply in the laboratory, either as an emergency test to alter patient management, or for those laboratories that wish to offer troponin T for selected cases but do not have the ability to measure troponin T quantitatively.

Atrial natriuretic factor: pharmacokinetics and cyclic GMP response in relation to biologic effects in severe heart failure.

The pharmacokinetics of synthetic atrial natriuretic factor (ANF) and its effects on cyclic GMP, urinary sodium excretion, and hemodynamics were compared in 18 control subjects with normal hemodynamics and 12 patients with severe heart failure. Human 99-126 ANF was administered intravenously (0.2 micrograms/kg i.v. followed by 0.07 micrograms/kg/min for 30 min). As compared with controls, baseline plasma ANF concentration was higher in the heart failure group (329.2 +/- 166.1 vs. 33.6 +/- 17.3 pg/ml in controls, means +/- SD, p less than 0.01). Synthetic ANF increased plasma ANF concentration by similar amounts, but the elimination half-life (t 1/2) for synthetic ANF was longer in the heart failure group (6.5 +/- 2.6 vs. 3.8 +/- 0.8 min, p less than 0.05). Baseline plasma cyclic GMP concentration was higher in the heart failure group (13.8 +/- 6.8 vs. 4.2 +/- 2.2 pmol/ml, p less than 0.01) but ANF increased plasma cyclic GMP concentration to a lesser degree (14.4 +/- 7.6 pmol/ml, p less than 0.05 vs. 24.9 +/- 10.1 pmol/ml, p less than 0.001). Baseline urinary sodium excretion was less in the heart failure group (13.3 +/- 14.0 vs. 53.7 +/- 37.3 mumol/min, p less than 0.01) and ANF induced a smaller increase in urinary sodium excretion (22.1 +/- 32.3 mumol/min, p less than 0.05 vs. 305.7 +/- 242.9 mumol/min, p less than 0.001). Baseline plasma norepinephrine (NE), renin, and aldosterone were higher in the heart failure group. Synthetic ANF increased plasma NE only in the control group, had no effect on renin, and decreased aldosterone in both groups. Hemodynamic responses were similar in both groups except the decreased arterial blood pressure (BP) was accompanied by increased heart rate (HR) only in the controls. Therefore, in heart failure, the t 1/2 of ANF is prolonged and there appears to be a limit for further increase in cyclic GMP. These changes may explain in part the blunted renal response to ANF.

Sequential changes in atrial pressures, dimensions, and plasma atrial natriuretic factor concentrations during volume loading in hemodynamically normal human subjects.

The effects of volume loading on atrial pressures and dimensions, plasma levels of atrial natriuretic factor (ANF), and other neurohormonal variables were studied in 11 patients with normal hemodynamics with the patients in a supine -15 degree left decubitus posture by infusing 750 ml of normal saline solution over 30 minutes. Right and left atrial areas were measured by two-dimensional echocardiography. Plasma ANF level was sampled simultaneously from the pulmonary artery, aorta, and femoral artery and vein. At 30 minutes into the infusion, pulmonary capillary wedge pressure and right atrial pressure increased from 5.6 +/- 2.8 mm Hg (mean +/- SD) and 6.4 +/- 2.2 mm Hg to 10.2 +/- 3.2 and 9.5 +/- 2.2 mm Hg, respectively (both p less than 0.01). Left atrial area increased from 12.6 +/- 2.2 cm2 to 15.0 +/- 2.1 cm2 (p less than 0.05), whereas right atrial area did not change. Plasma ANF levels from all sampling sites increased significantly (e.g., 43 +/- 21 pg/ml to 71 +/- 62 pg/ml in the femoral artery, p less than 0.05). Plasma norepinephrine and renin levels were unchanged, whereas aldosterone level declined significantly. At 30 minutes after termination of the infusion, atrial pressures declined to baseline values in all patients. However, left atrial area remained significantly increased, and a trend for systemic arterial plasma ANF level to remain increased was seen. Plasma aldosterone level remained significantly suppressed.(ABSTRACT TRUNCATED AT 250 WORDS)

Response of atrial natriuretic factor to postural change in patients with heart failure versus subjects with normal hemodynamics.

The response of atrial natriuretic factor to an acute increase in atrial pressures produced by changing from a 45 degrees upright to a -15 degrees Trendelenburg tilt was examined in 21 patients with heart failure and 8 control subjects with normal hemodynamics. In the control subjects, baseline (45 degrees upright tilt) pulmonary capillary wedge and right atrial pressures increased from 3.1 +/- 0.9 (mean +/- SEM) and 4.4 +/- 0.3 mm Hg to 6.9 +/- 1.9 and 8.5 +/- 0.4 mm Hg, respectively (p less than 0.05 for both), 30 min after the -15 degrees tilt. Baseline arterial plasma atrial natriuretic factor concentration increased from 34 +/- 4 to 44 +/- 1 pg/ml (p less than 0.05) 30 min after the tilt, with an increase observed in every patient. In the group with heart failure, baseline pulmonary capillary wedge and right atrial pressures increased from 17.5 +/- 2.0 and 5.3 +/- 1.2 mm Hg to 24.6 +/- 1.8 and 9.7 +/- 1.3 mm Hg, respectively (p less than 0.01 for both), 30 min after the tilt. Plasma atrial natriuretic factor concentration was 326 +/- 38 pg/ml at baseline and 347 +/- 34 pg/ml (p = NS) 30 min after tilt. Compared with the 7 patients with heart failure who had increased atrial natriuretic factor concentrations after the tilt (responders), the 14 patients with unchanged or decreased atrial natriuretic factor concentrations after the tilt (nonresponders) had a higher baseline right atrial pressure and atrial natriuretic factor concentrations.(ABSTRACT TRUNCATED AT 250 WORDS)

Atrial natriuretic peptide response to rapid atrial pacing in cardiac-denervated dogs.

The effects of rapid atrial pacing on central hemodynamics, plasma hormones, and renal function were investigated in eight control and nine cardiac-denervated dogs under chloralose anesthesia. Pacing at approximately 250 ppm for 60 min caused similar increases in pulmonary wedge and right atrial pressures, systemic vascular resistance, and plasma atrial natriuretic peptide (ANP) in both groups. In control dogs, pacing produced a fall in both plasma vasopressin (AVP) and plasma renin activity (PRA) and a rise in urine flow rate associated with an increase in free water but not sodium clearance. In contrast, in cardiac-denervated dogs, both plasma AVP and PRA increased during pacing; urine flow rate did not change, and marked sodium retention occurred. This study supports the concept that the increase in urine flow during rapid atrial pacing is mediated by inhibition of renin and AVP secretion through intact cardiac nerves. The secretion of ANP is unaffected by cardiac denervation. The natriuretic and vasodilator actions of high plasma ANP concentrations during rapid atrial pacing can be inhibited either by neurally mediated cardiorenal effects in normal animals or by stimulation of the renin-angiotensin system after cardiac denervation.

Atrial natriuretic peptide released by rapid ventricular pacing in dogs does not cause a natriuresis.

1. The relationships between the haemodynamic, renal and endocrine changes induced by rapid ventricular pacing were studied in ten chloralose-anaesthetized dogs paced from the right ventricular apex for 60 min at 250 beats/min. 2. Pacing increased mean right atrial and mean pulmonary wedge pressure (P less than 0.05), and decreased cardiac output and mean arterial pressure (P less than 0.05). 3. Coronary sinus atrial natriuretic peptide (ANP) concentrations were approximately fourfold greater than arterial concentrations; both increased markedly during pacing (P less than 0.01). Plasma concentrations of arginine vasopressin and plasma renin activity did not change significantly. 4. Urine flow and free water clearance increased during the latter 30 min of pacing (P less than 0.05). There was no significant change in sodium clearance despite high sustained concentrations of ANP. 5. Without the availability of specific inhibitors of ANP release or action, we are unable to exclude the possibility that ANP may have prevented sodium clearance from otherwise decreasing during rapid ventricular pacing. Nevertheless, the dissociation between elevated ANP concentrations and natriuresis in this study indicates that a rise in ANP concentrations per se is not sufficient to produce a natriuresis.

Continuous recording of coronary sinus oxygen saturation during atrial pacing in patients with coronary artery disease or with syndrome X.

Coronary sinus oxygen saturation was measured continuously during incremental atrial pacing in 34 patients undergoing cardiac catheterisation. In eleven patients with normal coronary arteriograms, negative exercise tests, and no ST segment depression on the electrocardiogram, an increase in the rate of atrial pacing transiently decreased coronary sinus oxygen saturation but within 20 s oxygen saturation returned to the control value. In six patients with coronary artery disease ST segment depression developed during atrial pacing. The coronary sinus oxygen saturation fell and remained reduced until pacing was discontinued. The size of the fall of coronary sinus oxygen saturation increased with increasing heart rate. In seven patients with coronary artery disease the ST segments were unaltered during atrial pacing and coronary sinus oxygen saturation did not fall. Ten patients with syndrome X were studied. In six ST segment depression developed on atrial pacing. In five, three of whom developed ST segment depression, the changes in coronary sinus oxygen saturation during atrial pacing were similar to those observed in patients without any evidence of coronary artery disease. In three, all of whom developed ST segment depression, coronary sinus oxygen saturation gradually increased throughout the period of atrial pacing. In two patients coronary sinus oxygen saturation fell in a manner similar to that observed in patients with obstructive coronary artery disease who developed ST segment depression on pacing. Thus regulation of coronary blood flow in normal persons in response to an increase of heart rate is rapid. Oxygen extraction across the coronary bed can increase by up to 30% and a persistent increase in oxygen extraction is an indicator of myocardial ischaemia. The term "syndrome X" does not describe a homogeneous group of patients but in the majority coronary sinus oxygen saturation does not fall despite symptoms and changes on the electrocardiogram, indicating that inadequate coronary blood flow is not the dominant mechanism.

Effects of endogenous atrial natriuretic peptide released by rapid atrial pacing in dogs.

The relationships between the hemodynamic, renal, and endocrine changes induced by rapid atrial pacing were studied in seven chloralose-anesthetized greyhounds paced from the right atrial appendage for 60 min at 250 beats/min. Pacing increased mean pulmonary wedge pressure, decreased cardiac output, and decreased mean arterial pressure. Systemic vascular resistance did not change significantly. Coronary sinus atrial natriuretic peptide (ANP) concentrations rose maximally within 5 min of commencing pacing. The corresponding increase in arterial ANP concentrations during this time was only 44% of its maximum value after 30 min of pacing. Plasma concentrations of arginine vasopressin were unchanged. Plasma renin activity decreased during pacing and showed a marked rebound increase at 60 min postpacing. Plasma norepinephrine levels did not change significantly during pacing. Urine flow increased during the latter 30 min of pacing. There was no significant change in sodium clearance despite high sustained concentrations of ANP. The lack of significant natriuretic and systemic vasodilator effects in association with high arterial plasma concentrations of endogenous ANP, in the absence of antagonistic mechanisms, suggests that the natriuretic and vascular effects of ANP may not be its major physiological actions.

Aorta-right atrial fistula: an unusual complication of ascending aortic dissection.

Ascending aortic dissection complicated by aorta-right atrial fistula is a very rare occurrence. The patient may present with atypical clinical findings such as a continuous murmur or atrioventricular block, making the diagnosis difficult. Surgical repair is straightforward unless the correct diagnosis is missed, in which case there may be difficulties during the initial period of cardiopulmonary bypass. This report deals with the successful management of a 67-year-old man with this condition.

Myocardial potassium loss after acute coronary occlusion in humans.

Animal studies have established that there is a rapid increase in extracellular potassium concentration in myocardial tissue after the onset of ischemia. To study this phenomenon in humans, coronary sinus plasma potassium concentration was measured in five patients undergoing therapeutic coronary angioplasty. Recordings were obtained during a total of 22 coronary artery occlusions lasting between 5 and 50 seconds. Though little change was observed during angioplasty balloon inflation, all occlusions that lasted more than 15 seconds were followed by a transient elevation in coronary sinus potassium concentration of between 0.18 and 1.55 mmol X liter-1. The majority of occlusions (n = 17) were not accompanied by chest pain, electrocardiographic (ECG) changes or alteration of heart rate. The increase in coronary sinus potassium concentration after angioplasty balloon deflation is attributable to a washout of accumulated extracellular potassium during reperfusion. Redistribution of human myocardial potassium occurs within 15 seconds of the onset of myocardial ischemia and may be an important factor accounting for early electrophysiologic changes.

Differences between acute and long-term metabolic and endocrine effects of oral beta-adrenoceptor agonist therapy with pirbuterol for cardiac failure.

The metabolic, hormonal and haemodynamic effects of oral pirbuterol, a new beta 2-adrenoceptor agonist, were studied acutely (n = 19) and after 3 months treatment (n = 11) in patients with severe heart failure receiving chronic frusemide therapy. In the acute study fasted patients (n = 10) showed reductions in plasma K+ (P less than 0.005) and cortisol (P less than 0.01) and increases in plasma glucose (P less than 0.005), insulin (P less than 0.01), lactate (P less than 0.005) and pyruvate (P less than 0.0025). These acute changes were less in unfasted subjects (n = 9). Maximal increase in stroke volume occurred at approximately half the plasma pirbuterol concentration required for maximal effect on plasma insulin. Treatment with pirbuterol for 3 months was associated with sustained increases in stroke volume and fasting plasma glucose and insulin, but there was loss of all other acute metabolic effects. Despite concurrent frusemide and digoxin therapy acute hypokalaemia caused no adverse effects. Hypokalaemia did not occur with chronic pirbuterol administration.

Untreated heart failure: clinical and neuroendocrine effects of introducing diuretics.

The clinical and neuroendocrine response to diuretic treatment was assessed at rest and on exercise in 12 patients with heart failure. Before treatment all patients were limited by breathlessness on exercise; one was oedematous. Plasma renin activity and aldosterone were normal but plasma noradrenaline was raised both at rest and on exercise. After one month's treatment with frusemide (40 mg) and amiloride (5 mg) weight was significantly reduced by a mean of 3.5 kg and exercise capacity had doubled. Plasma noradrenaline fell to normal at rest but remained abnormally raised on exercise. Plasma renin activity and aldosterone increased significantly both at rest and on exercise. Diuretics bring about a considerable clinical improvement in patients with chronic heart failure but they stimulate the renin-angiotensin system. Activation of the renin-angiotensin system in moderate heart failure occurs as a response to diuretic treatment rather than as a result of the disease process itself.

The renal response to neuroendocrine inhibition in chronic heart failure: double-blind comparison of captopril and prazosin.

Activation of the renin-angiotensin and sympathetic systems in chronic heart failure causes important renal vasoconstriction. In a double-blind cross-over study, treatment with captopril for one month reduced systemic and renal vascular resistance by 14% and 25%, increased renal blood flow by 12%, and increased the percentage of the cardiac output perfusion to the kidney by 13%. Treatment with prazosin for one month also reduced systemic vascular resistance by 8%, renal vascular resistance increased by 20%, and renal blood flow and the percentage of the cardiac output going to the kidney fell by 14% and 26%. During captopril treatment, plasma aldosterone concentration was reduced to normal, but during prazosin treatment there was an initial increase in aldosterone of 45%, and a sustained increase in plasma noradrenaline concentration of 26%. Body weight decreased by 1.7 kg on captopril, but increased by 3.0 kg on prazosin, correlating inversely with the changes in renal blood flow. Sympathetic inhibition with prazosin causes systemic vasodilatation which diverts blood from the kidney and may result in fluid retention. Inhibition of the renin system with captopril causes preferential renal vasodilatation and can improve renal perfusion in chronic heart failure.

Factors determining symptoms in heart failure: comparison of fast and slow exercise tests.

Factors determining the symptoms of breathlessness and fatigue in patients with congestive heart failure were investigated by comparing the response to slow and fast exercise. Symptom limited oxygen consumption (maximal); minute ventilation, mean pulmonary capillary wedge pressure; and arterial blood gases, pH, and lactate concentrations were measured during treadmill exercise using a slow protocol in 25 men (age 34-67 years) with congestive heart failure (New York Heart Association class II-III). Ten of these patients were also exercised according to a rapid protocol. Exercise was terminated by fatigue in 23/25 patients after the slow test and by breathlessness in all patients after the rapid test. Exercise capacity (maximal oxygen consumption and exercise duration) was not related to resting or exercise pulmonary capillary wedge pressure or the change in pulmonary capillary wedge pressure during exercise, nor was there any difference in pulmonary capillary wedge pressure at the end of exercise within individuals between the fast and slow tests. Minute ventilation was greater (51 vs 43 1/min), peak exercise lactate concentration higher (3.7 vs 2.2 mmol/l), and the change in pH from the resting state was greater (0.06 vs 0.02) during the rapid test than during the slow test. The sensation of breathlessness in congestive heart failure is not simply related to raised pulmonary capillary wedge pressure, but may in part be due to stimulation of peripheral chemoreceptors in response to metabolic acidosis.