Prognostic value of two-dimensional echocardiography and N-terminal proatrial natriuretic peptide following an acute myocardial infarction. Assessment of baseline values (2-7 days) and changes at 3 months in patients with a preserved systolic function.

AIMS: The purpose of this prospective, observational study was to evaluate the relationship of left ventricular volumes, systolic function and plasma N-terminal proatrial natriuretic peptide (Nt-proANP) to cardiac morbidity and mortality in post-myocardial infarction patients with left ventricular ejection fraction > or =40%. METHODS AND RESULTS: Two-dimensional echocardiographic recordings and Nt-proANP measurements were obtained in 834 patients who survived acute myocardial infarction. Patients were examined at 2-7 days and 3 months after the index infarction and followed up for 24 months. All measurements of left ventricular volumes, ejection fraction and Nt-proANP were performed in core laboratories. During follow-up 102 patients sustained one or more incidents of the combined primary end-point: cardiac death (n=11), recurrent infarction (n=55) or heart failure requiring hospitalization or treatment with an ACE inhibitor and a diuretic (n=52). Using Cox proportional hazards model, baseline Nt-proANP predicted these events (chi-square 25.3, P<0.0001), while baseline echo volumes and ejection fraction did not. During the subsequent 3-24 month period, 51 patients suffered a primary end-point: cardiac death (n=9), recurrent infarction (n=29), heart failure (n=21). An increase in left ventricular end-systolic volume was the strongest predictor for adverse events (chi-square 19.1, P<0.0001), especially for heart failure. Individual changes in Nt-proANP did not predict cardiac events, whereas both echocardiographic variables and Nt-proANP measured at 3 months had a prognostic impact on subsequent cardiac events (3-24 months). CONCLUSIONS: In post-myocardial infarction patients with preserved left ventricular function (left ventricular ejection fraction > or =40%) baseline Nt-proANP, but not echocardiographic left ventricular volumes predicted adverse cardiac events. Early changes in left ventricular volumes and ejection fraction from baseline to 3 months had a further prognostic impact on subsequent events (3-24 months).

Accuracy and reproducibility of biplane two-dimensional echocardiographic measurements of left ventricular dimensions and function.

OBJECTIVE: To investigate sources of variability in serial echocardiographic recordings in a core laboratory we assessed the impact of repeated echo recordings, repeated video measurements and measurements made by different investigators. PATIENTS, METHODS: Two investigators each recorded and analysed two-dimensional echos in 12 individuals (n = 24 in total) three times at one week intervals. Left ventricular end-diastolic and end-systolic volumes were measured using the biplane modified Simpson's rule. Ejection fraction was derived from these volumes and left ventricular mass estimated using the area-length method. The left ventricular spherity index was expressed as the ratio of the short axis area and the long axis area at end-diastole. A video recording from each examination was reexamined twice by both investigators. RESULTS: Deviations between repeated echo recordings and repeated video measurements ranged from -5 to +5% between investigators. A three-way repeated analysis of variance indicated a small, but systematic difference between investigators. Reproducibility, measured by coefficients of variation, ranged from 3-9% for different investigators, 3-6% for repeated video measurements and 7-19% for repeated echo recordings across the different variables. The total variability of all three factors should be considered when the smallest detectable significant change in a variable is assessed. These ranged from 16-28% across the five variables studied, when a 10% error of classification was accepted for a one-sided change in a variable. CONCLUSION: Repeated echo recordings were the dominant component of variation. Two-dimensional echo measurements are reproducible and accurate, but the same investigator should follow the same patients.

Changes in left ventricular dimensions and haemodynamics during antihypertensive treatment with spirapril for 36 months.

To assess the long-term course of regression of left ventricular hypertrophy (LVH) and haemodynamic changes during spirapril treatment, 11 male hypertensive patients with a left ventricular mass (LVM) > 240 g and a mean age of 48 (range 41-60) years were followed-up with echo-Doppler examinations for 36 months. The initial spirapril dose was 6 or 12 mg once daily, which was titrated to a minimum of 3 mg and a maximum of 24 mg to keep diastolic blood pressure (DBP) < or = to 95 mmHg. Patient compliance based on tablet counts was 98% (range 95-100%). The mean spirapril dose was 9 +/- 6 mg at 3 months, 9 +/- 6 mg at 12 months, and 15 +/- 9 mg at 36 months. Blood pressure was reduced from 161 +/- 20/107 +/- 6 mmHg at baseline to 137 +/- 11/89 +/- 6 mmHg at 3 months (p < 0.001), 141 +/- 20/89 +/- 4 mmHg at 12 months and 135 +/- 11/87 +/- 6 mmHg at 36 months. The respective values for LVM at baseline and at 3, 12 and 36 months were 340 +/- 71 g, 305 +/- 61 g (p < 0.05 vs baseline), 303 +/- 88 g and 298 +/- 94 g. Cardiac output did not change whereas systemic arteriolar resistance (SAR) was significantly reduced after 3 and 36 months (p < 0.01). Thus, the regression of LVH with spirapril was 10% of LVM at 3 months, 11% at 12 months, and 12% at 36 months. These changes were mainly related to a reduction of LV posterior wall thickness and SAR.

Left ventricular end-diastolic dimensions measured at the P wave and Q wave during a randomized, double-blind one-year follow-up study comparing the effect of atenolol vs. hydrochlorothiazide + amiloride on blood pressure in men with mild to moderate hypertension.

Echocardiographic measurement of left ventricular (LV) end-diastolic dimensions and mass (M) were made at baseline, at 3 and 12 months of a randomized trial comparing atenolol 50/100 mg od. and hydrochlorothiazide 25/50 mg+amiloride 5 mg od. (co-amiloride) in 100 men with mild to moderate hypertension. Data from 48 subjects controlled adequately on drug monotherapy and completing 12 months treatment are reported (31 randomized to atenolol and 17 to co-amiloride). Left ventricular mass was measured with the Penn convention at the R and P wave respectively. A significant reduction of LVM was noted after one year in both groups (p < 0.05) when measured at the R, but not at the P wave. Measurements according to American Society of Echocardiography (ASE method) at the Q wave revealed a significant reduction of LV wall thickness (p < 0.01) and an increase of LV internal diameter (p < 0.01) with atenolol. In the co-amiloride group non-significant reductions of LV dimensions were observed. Principally similar changes were observed with measurements at the P wave (National Institute of Heart method) in both groups, but LV wall thickness was greater and LV internal diameter smaller than at the Q wave. With similar effect on LVM, the mechanisms in reducing LVM were different between the two drugs. Left ventricular dimensions differed when assessed with the two methods applied, stressing the need for careful standardization in relation to the cardiac cycle in serial echocardiographic measurements.

Haemodynamic findings and response rates to beta-blocker--and diuretic monotherapy in mild and moderate hypertension. A one year randomized, double blind study in 100 men.

In a randomized double blind study 100 men (mean age 46 (22-64) years) with mild to moderate hypertension were followed every 3rd month for one year. Fifty were randomized to atenolol 50 mg and 50 to hydrochlorothiazide 25 mg+amiloride 5 mg (co-amiloride) once daily. The doses were doubled at 3 or 6 months if diastolic blood pressure (DBP) remained > or = 95 mmHg. If DBP was > or = 95 mmHg even at 6 or 9 months, patients were classified as non-responders, and nifedipine 20 mg b.i.d. was added. After one year 31/50 randomized to atenolol and 17/50 randomized to co-amiloride had responded to monotherapy (p < 0.05). Neither clinical findings nor haemodynamic measurements by Doppler at baseline could distinguish between co-amiloride responders and non-responders. Conversely, non-responders to atenolol as compared with atenolol responders had higher body weight (p = 0.02), higher systolic BP (p = 0.03), higher DBP (p = 0.009), stroke volume (p = 0.04), and cardiac output (p = 0.0002) combined with lower total systemic vascular resistance (p = 0.02). This suggests that some were apparent non-responders due to too low dosing of atenolol rather than true non-responders. Measurements of haemodynamics may be of importance in the assessment of optimal antihypertensive therapy according to baseline and follow-up haemodynamic aberrations.

Changes in left ventricular dimensions and systolic function in 100 mildly hypertensive men during one year's treatment with atenolol vs. hydrochlorothiazide and amiloride (Moduretic): a double-blind, randomized study.

In a randomized double-blind study to compare the effect of atenolol vs. hydrochlorothiazide and amiloride (Moduretic) on left ventricular dimensions and systolic function, 100 hypertensive men were followed up during 1 year of treatment, 50 subjects being randomized to each drug. Echocardiography was performed at baseline, and after 3 and 12 months of treatment. A significant reduction in left ventricular mass with atenolol was paralleled by a decrease in left ventricular wall thickness and an increase in stroke volume. A similar reduction of left ventricular mass with Moduretic without a change in relative wall thickness and a decrease in stroke volume was observed. Cardiac output decreased in both groups.

Lipid profile in 100 men with moderate hypertension treated for 1 year with atenolol or hydrochlorothiazide plus amiloride: a double-blind, randomized study.

A double-blind randomized study comparing the effects of 1 year's treatment with atenolol (A) 50 mg or hydrochlorothiazide 25 mg plus amiloride 5 mg (Moduretic (M)) on the lipid profile was performed in 100 hypertensive men (mean age 47, range 22-64 years). After 4 weeks' wash-out and 4 weeks on placebo therapy subjects were randomized to either A or M therapy and followed up every third month for 1 year. If the diastolic blood pressure (DBP) was greater than or equal to 95 mmHg at a subsequent visit, the doses were doubled (n = 17 for A and n = 12 for M) and, if DBP was still greater than or equal to 95 mmHg on double dose, nifedipine 20 mg b.d. was added (n = 15 for A and n = 27 for M, p less than 0.05). The lowering of heart rate (p = 0.0001) and DBP (p = 0.005) was more pronounced with A after 1 year. During that time no significant treatment differences were noted for total cholesterol, low-density lipoprotein (LDL) cholesterol or apoproteins A and B. High-density lipoprotein (HDL) cholesterol decreased from a mean of 1.19 (+/- 0.36) mmol l-1 to 1.13 (+/- 0.35) with A, and increased from 1.14 (+/- 0.30) mmol l-1 to 1.22 (+/- 0.28) with M, and this treatment difference was significant (p = 0.0002). The triglycerides increased from 2.0 (+/- 1.2) mmol l-1 to 2.3 (+/- 1.6) in the A group and did not change with M treatment (p = 0.02) for treatment difference). In view of similar effects on cholesterol, LDL cholesterol and apoproteins, the prognostic importance of the observed treatment differences on HDL cholesterol and triglycerides remains to be established.

Validity of the ECG diagnosis of left ventricular hypertrophy in normotensive and moderately hypertensive men when using the echocardiographic assessment of left ventricular mass index as reference.

The diagnostic validity of ECG criteria for left ventricular hypertrophy (LVH) was assessed in 100 men aged 22-64 (mean 47) years with moderate hypertension (Group 1) and 95 age-matched normotensive men (Group 2) using echocardiographic recordings of LV mass index (MI) as reference. A diagnosis of LVH was made in subjects with LVMI greater than or equal to 125 g/m2. Mean LVMI was 126 +/- 34 g/m2 in Group 1 vs. 100 +/- g/m2 in Group 2 (P less than 0.001), and the prevalence of LVH was 48% and 11% respectively (P less than 0.001). The mean ECG voltage according to Sokolow-Lyon (S-L) was 28 +/- 8 mm in Group 1 and 27 +/- 7 mm in Group 2 (NS); with 19% having LVH in Group 1 and 14% in Group 2 (NS). Using the Cornell criterion Group 1 had on average 15 +/- 6 mm vs. 12 +/- 5 mm in Group 2 (P less than 0.001), but only two Group 1 patients had LVH. In Group 2 a significant negative correlation between age and S-L voltage was found (r = 0.33, P less than 0.001). LVMI was not correlated with any of the two voltage criteria using linear regression analysis whereas multiple regression analysis revealed a weak, but significant correlation between LVMI and S-L voltage in Group 1 (t = 2.06, P = 0.04). No subject had LV strain pattern or LVH according to the Romhilt Estes point score system. In the assessment of possible LVH in normal or moderately hypertensive men less than 65-70 years of age, ECG has limited value.