John G. Turner

Plasma N-Terminal Pro–Brain Natriuretic Peptide and Adrenomedullin New Neurohormonal Predictors of Left Ventricular Function and Prognosis After Myocardial Infarction

BACKGROUND Newly discovered circulating peptides, N-terminal pro-brain natriuretic peptide (N-BNP) and adrenomedullin (ADM), were examined for prediction of cardiac function and prognosis and compared with previously reported markers in 121 patients with myocardial infarction. METHODS AND RESULTS The association between radionuclide left ventricular ejection fraction (LVEF) and N-BNP at 2 to 4 days (r=-.63, P<.0001) and 3 to 5 months (r=-.58, P<.0001) after infarction was comparable to that for C-terminal BNP and far stronger than for ADM (r=-.26, P<.01), N-terminal atrial natriuretic peptide (N-ANP), C-terminal ANP, cGMP, or plasma catecholamine concentrations. For prediction of death over 24 months of follow-up, an early postinfarction N-BNP level > or = 160 pmol/L had sensitivity, specificity, positive predictive value, and negative predictive values of 91%, 72%, 39%, and 97%, respectively, and was superior to any other neurohormone measured and to LVEF. Only 1 of 21 deaths occurred in a patient with an N-BNP level below the group median (Kaplan-Meier survival analysis, P<.00001). For prediction of heart failure (left ventricular failure), plasma N-BNP > or = 145 pmol/L had sensitivity (85%) and negative predictive value (91%) comparable to the other cardiac peptides and was superior to ADM, plasma catecholamines, and LVEF. By multivariate analysis, N-BNP but not ADM provided predictive information for death and left ventricular failure independent of patient age, sex, LVEF, levels of other hormones, and previous history of heart failure, myocardial infarction, hypertension, or diabetes. CONCLUSIONS Plasma N-BNP measured 2 to 4 days after myocardial infarction independently predicted left ventricular function and 2-year survival. Stratification of patients into low- and high-risk groups can be facilitated by plasma N-BNP or BNP measurements, and one of these could reasonably be included in the routine clinical workup of patients after myocardial infarction.

Plasma brain natriuretic peptide in assessment of acute dyspnoea

Recognition of heart failure (HF) may be difficult in patients presenting with acute dyspnoea, particularly in the presence of chronic airways obstruction. Since increased secretion of the cardiac hormones atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) occurs early in the course of HF, we have assessed the value of measuring these hormones in plasma in the diagnosis of suspected HF in 52 elderly patients presenting with acute dyspnoea, and compared values with left-ventricular ejection fraction (LVEF), a standard measure of left-ventricular function, by radionuclide angiography. Patients were enrolled prospectively. On the basis of clinical findings, conventional tests, and response to specific treatment, 20 of the 52 patients were classified as having primary lung disorder (PLD), 12 as HF alone, and 20 as HF with underlying PLD (HF/PLD). Compared with findings in PLD patients, LVEF was significantly depressed in HF and HF/PLD patients (p < 0.001), whereas both plasma ANP and BNP were significantly increased (p < 0.001). Admission plasma BNP concentration more accurately reflected the final diagnosis of HF (93% sensitivity and 90% specificity when BNP > or = 22 pmol/L) than LVEF or plasma ANP concentration. When all patients were considered together, there were strong negative correlations between LVEF and log BNP (r = -0.7, p < 0.001) and log ANP (r = -0.59, p < 0.001). Our finding that plasma BNP is raised in dyspnoeic patients with HF but not in acutely breathless patients with PLD, suggests that rapid BNP assays may assist in the diagnosis of patients with acute dyspnoea.

B-Type Natriuretic Peptides and Ejection Fraction for Prognosis After Myocardial Infarction

Background—A recent landmark report has demonstrated that plasma B-type natriuretic peptide (BNP) measured in acute coronary syndromes independently predicts mortality, heart failure, and new myocardial infarction. After acute cardiac injury, left ventricular ejection fraction (LVEF) is also of prognostic significance and plays a major role in determining the therapeutic response. Methods and Results—The present report is the first from a substantial (n=666) cohort of patients with acute myocardial infarction to test the prognostic utility of concurrent measurements of BNP, amino-terminal BNP (N-BNP), norepinephrine, and radionuclide LVEF. The B-type peptides and LVEF were predictors of death, heart failure, and new myocardial infarction (all P <0.001) independent of patient age, gender, previous myocardial infarction, antecedent hypertension or diabetes, previous heart failure, plasma norepinephrine, creatinine, cholesterol, drug therapy, and coronary revascularization procedures. The combination of N-BNP (or BNP) with LVEF substantially improved risk stratification beyond that provided by either alone. Elevated N-BNP (or BNP) predicted new myocardial infarction only in patients with LVEF <40%. LVEF <40% coupled to N-BNP over the group median conferred substantial 3-year risks of death, heart failure, and new myocardial infarction of 37%, 18%, and 26%, respectively. N-BNP and BNP were equivalent prognostic markers for these clinical outcomes. Conclusions—Plasma N-BNP (or BNP) and LVEF are complementary independent predictors of major adverse events on follow-up after myocardial infarction. Combined measurement provides risk stratification substantially better than that provided by either alone.

Neuroendocrine prediction of left ventricular function and heart failure after acute myocardial infarction

Objective To determine the relations of plasma levels of brain natriuretic peptide (BNP), atrial natriuretic factor (ANF), N-terminal ANF (N-ANF), cyclic guanosine monophosphate (cGMP; the cardiac peptide second messenger), and plasma catecholamines to left ventricular function and to prognosis in patients admitted with acute myocardial infarction. Design Plasma hormones and ventricular function (radionuclide ventriculography) were measured 1–4 days after myocardial infarction in 220 patients admitted to a single coronary care unit. Radionuclide scanning was repeated 3–5 months after infarction. Clinical events were recorded over a mean period of 14 months. Results Both early and late left ventricular ejection fraction (LVEF) were most closely related to plasma BNP (r = −0.60, n = 220, p < 0.001; andr = −0.53, n = 192, p < 0.001, respectively), followed by ANF, N-ANF, cGMP, and the plasma catecholamines. Early plasma BNP concentrations less than twofold the upper limit of normal (20 pmol/l) had 100% negative predictive value for LVEF < 40% at 3–5 months after infarction. In multivariate analysis incorporating all the neurohormonal factors, only BNP remained independently predictive of LVEF < 40% (p < 0.005). Survival analysis by median levels of candidate predictors identified BNP as the most powerful discriminator for death (p < 0.0001). No early deaths (within 4 months) occurred in patients with plasma BNP concentrations below the group median (27 pmol/l), and over follow up only three of 26 deaths occurred in this subgroup. Of all episodes of left ventricular failure, 85% occurred in patients with plasma BNP above the median (p < 0.001). In multivariate analyses, BNP alone gave additional predictive information beyond sex, age, clinical history, LVEF, and plasma noradrenaline for both subsequent onset of LVF and death. Conclusions Plasma BNP measured within 1–4 days of acute myocardial infarction is a powerful independent predictor of left ventricular function, heart failure, or death over the subsequent 14 months, and superior to ANF, N-ANF, cGMP, and plasma catecholamines.

Antecedent hypertension and heart failure after myocardial infarction

OBJECTIVES We sought to assess the relationship of antecedent hypertension to neurohormones, ventricular remodeling and clinical heart failure (HF) after myocardial infarction (MI). BACKGROUND Heart failure is a probable contributor to the increased mortality observed after MI in those with antecedent hypertension. Hence, neurohormonal activation, adverse ventricular remodeling and a higher incidence of clinical HF may be expected in this group. However, no previous report has documented serial postinfarction neurohumoral status, serial left ventricular imaging and clinical outcomes over prolonged follow-up in a broad spectrum of patients with and without antecedent hypertension. METHODS Inpatient events were documented in 1,093 consecutive patients (436 hypertensive and 657 normotensive) with acute MI. In 68% (282 hypertensive, 465 normotensive) serial neurohormonal sampling and radionuclide ventriculography were performed one to four days and three to five months after infarction. Clinical outcomes were recorded over a mean follow-up of two years. RESULTS Plasma neurohormones were significantly higher in hypertensives than in normotensives one to four days and three to five months after infarction. From similar initial values, left ventricular volumes increased significantly in hypertensives, compared with normotensives. Left ventricular ejection fraction rose significantly in normotensive but not hypertensive patients. Together with higher inpatient (8.1% vs. 4.4%, p < 0.002) and post-discharge mortality (9.5% vs. 5.5%, p = 0.043), hypertensive patients incurred more inpatient HF (33% vs. 24%, p < 0.001) and more late HF requiring readmission to hospital (12.4% vs. 5.5%, p < 0.001). Antecedent hypertension predicted late HF in patients >64 years of age with neurohormonal activation and early left ventricular dilation. CONCLUSIONS Antecedent hypertension interacts with age, neurohumoral activation and early ventricular remodeling to confer greater risk of HF after MI.

Lithium associated thyrotoxicosis: a report of 14 cases, with statistical analysis of incidence

OBJECTIVE Lithium is known to cause goitre and hypothyroidism, and has been associated less commonly with hyperthyroidism. We report a series of 14 patients with lithium associated thyrotoxicosis (LiAT), and have used epidemiological data to assess the association between long‐term lithium treatment and the development of thyrotoxicosis.

Assessment of Creatinine Clearance in Healthy Subjects over 65 Years of Age

Eighteen healthy people over 65 years of age were studied to compare the 99mTC-diethylenetriamine pentaacetic acid (DTPA) clearance, the measured 24-hour creatinine clearance and the assessed creatinine clearance using the Cockcroft and Gault (C-G) formula to measure their glomerular filtration rate. Significant correlations were found between the isotopic method and the measured creatinine clearance (r = 0.71; p less than 0.001); the measured creatinine clearance and the C-G formula (r = 0.81; p less than 0.001), and the isotopic method and the C-G formula (r = 0.70; p less than 0.001). The C-G formula correlated better with both the 99mTc-DTPA clearance and the measured creatinine clearance when the female correction factor was used. This study has shown that in healthy, elderly people, the C-G formula for assessing the creatinine clearance correlated extremely well with the standard clinical tests for measuring the glomerular filtration rate. Whilst the formula has clinical value and allows rapid and accurate assessment of renal function in the elderly, the clinician must be aware that the formula relatively underestimates the true renal clearance.

LITHIUM AS AN ADJUNCT TO RADIOIODINE THERAPY FOR THYROTOXICOSIS

16 patients with diffuse thyroid hyperplasia were given lithium carbonate (400 mg daily) for 1 week before and 1 week after a standardised 5 mCi therapy dose of 131I. A comparable control group of 16 patients were treated with 5 mCi of 131I without lithium therapy. The % retention of the therapy dose was measured in all patients at 7 days (168-hour 131I uptake). In the lithium-treated group the 24-hour 131I uptake showed no significant change after the first week of lithium therapy. The mean 48-hour protein-bound 131I, however, fell considerably from 1-21 to 0.55%/dose/1. The mean 24-168 hour % thyroidal 131I uptake drop was significantly less in the lithium group. These results show that low-dosage lithium therapy increases the retention of a standard-therapy dose of 131I. Lithium promises to be a useful adjunct to 131I therapy in patients with a rapid thyroidal iodine turnover and particularly in young patients where the total body-radiation dose must be kept to a minimum.

Comparison of enalapril versus captopril on left ventricular function and survival three months after acute myocardial infarction (the “practical” Study)

Left ventricular (LV) function and survival can be improved with captopril when initiated later than 24 hours after acute myocardial infarction. Animal studies suggest additional benefits may be obtained with earlier initiation of angiotensin-converting enzyme (ACE) inhibitors. The effects on LV function of captopril and enalapril initiated within 24 hours of myocardial infarction were studied. Two hundred twenty-five patients with acute myocardial infarction were enrolled within 24 hours of the onset of chest pain. They were randomized to receive either captopril 25 mg three times daily, enalapril 5 mg three times daily, or placebo. LV ejection fraction (EF) and volumes were measured by radionuclide ventriculography at baseline during treatment and at 3 months after a 3-day withdrawal from therapy. The ACE inhibitor group had a significant increase in EF (45 +/- 1 to 47 +/- 1%; p = 0.005) and significantly attenuated LV dilatation compared with results in the placebo group (175 +/- 6 to 189 +/- 7 ml in the placebo group vs 168 +/- 4 to 172 +/- 4 ml in the ACE inhibitor group; p = 0.051 for LV end-diastolic volume; and 99 +/- 6 to 108 +/- 7 ml in the placebo group vs 94 +/- 3 to 94 +/- 4 ml; p = 0.026 for LV end-systolic volume). The beneficial effects of ACE inhibitor therapy on LV function were observed irrespective of the degree of initial LV dysfunction and were comparable in both the captopril and enalapril groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Subclinical thyrotoxicosis in an outpatient population – predictors of outcome

Objective  Individuals with endogenous subclinical thyrotoxicosis (SCT) may subsequently require treatment for overt disease. We aimed to evaluate the frequency of progression to hyperthyroidism and factors influencing this outcome.