Cardiac dimension and function in patients with childhood onset growth hormone deficiency,before and after growth hormone retreatment in adult age

Background Growth hormone (GH) replacement during childhood has been shown to increase stature; however, there is little information on its long-term effect on the heart is not yet clear. The aim of this study was to assess cardiac size and function in patients with childhood-onset GH deficiency in whom GH treatment had been stopped at the achievement of final height and the effect of a second course of GH replacement in adult age. Methods Cardiac dimensions and function, obtained with echocardiography, of 21 patients (5 women and 16 men, mean age 28 ± 8 years), all of whom were treated during childhood, were compared with 21 age- and sex-matched healthy control subjects. Eight of these patients (2 women and 6 men, mean age 28 ± 8 years) were given a second course of GH replacement therapy for 15 ± 3 months. Results The stature and all cardiac dimensions of patients with GH deficiency who were treated during childhood were significantly smaller than those of the control subjects. After the second course of GH in adulthood, the only significant change observed was an increase in left ventricular (LV) mass (93 ± 21 vs 106 ± 24 g, P = .007) and LV mass index (59 ± 12 vs 66 ± 13 g/body surface area, P = .005). Conclusion The stature and cardiac dimensions of patients with childhood-onset GH deficiency measured in adult age were smaller than those of control subjects, despite long-term GH replacement therapy during childhood. A second course of GH treatment during adulthood caused a significant increase in the estimated LV mass index in patients with both isolated and multiple pituitary hormone deficiency. (Am Heart J 2003;145:549-53.)     

Wasting of the left ventricle in patients with cardiac cachexia: a cardiovascular magnetic resonance study

BACKGROUND: The "cachectic heart" has been described as a pathologic decrease in the size and mass of the heart, but no in vivo studies have shown changes in cardiac dimensions or left ventricular (LV) mass over time in chronic heart failure (CHF) associated with body wasting (cardiac cachexia). Cardiovascular magnetic resonance (CMR) has high reproducibility and is more sensitive than other techniques. METHODS: CMR studies of LV volumes and mass were performed at baseline and a mean of 15 months later in nine CHF patients with cardiac cachexia and 28 matched CHF controls without cachexia (mass index 23 +/- 1 vs. 29 +/- 5 kg/m2, P=0.0005). RESULTS: At baseline, LV end-diastolic volume (197 +/- 78 vs. 203 +/- 65 ml), end-systolic volume (131 +/- 75 vs. 126 +/- 63 ml), LV mass (213 +/- 44 vs. 222 +/- 62 g), and LV ejection fraction (38 +/- 19% vs. 40 +/- 16%) did not differ between cachectic patients and controls (all P>0.10). During follow-up, there was a significant decrease in LV mass in patients with cachexia (-16 g, P<0.05) and a trend to increase in LV mass in patients without cachexia (+7 g, P=0.12, comparison between groups: P=0.010). CONCLUSIONS: The direction of changes over time in LV mass differs in CHF patients with cachexia as compared with non-cachectic controls. A significant decrease in LV mass occurs in patients with cardiac cachexia. This study documents in vivo the occurrence of wasting of the left ventricle in patients with CHF who demonstrate general body wasting.     

Change of left ventricular geometric pattern after 1 year of antihypertensive treatment: the Losartan Intervention For Endpoint reduction in hypertension (LIFE) study

Background Patients with hypertension have different types of left ventricular (LV) geometry, but the impact of blood pressure (BP) reduction on LV geometry change during antihypertensive treatment remains unclear. Methods Two-dimensional and M-mode echocardiograms were recorded at baseline in 853 unmedicated patients with stage II to III hypertension and LV hypertrophy determined by electrocardiography (Cornell voltage duration ≥2440 mV × ms or modified Sokolow-Lyon criteria: SV1 + RV5/RV6 >38 mV) after 14 days of placebo treatment. Follow-up echocardiography was done after 1 year of blinded treatment with either losartan or atenolol, in some cases supplemented with thiazide and calcium antagonist to reach target a BP of 140/90 mm Hg. Results Baseline systolic/diastolic BP were reduced from 174 ± 20/95 ± 11 to 151 ± 19/84 ± 11 mm Hg. LV mass was reduced from 234 ± 56 to 207 ± 51 g and relative wall thickness from 0.41 ± 0.07 to 0.38 ± 0.06 (all P < .001). Prevalence of concentric LV hypertrophy decreased from 24% to 6%, eccentric LV hypertrophy from 46% to 37%, and concentric LV remodeling from 10% to 6%; normal geometry increased from 20% to 51%. A shift toward lower LV mass and relative wall thickness was found, as approximately 73% of those with concentric LV remodeling at baseline shifted to normal geometric pattern, whereas only 7% of those with normal pattern at baseline shifted to concentric LV remodeling. Of patients with concentric LV hypertrophy at baseline, 34% shifted to eccentric LV hypertrophy, whereas only 3% with eccentric LV hypertrophy at baseline had concentric LV hypertrophy. Furthermore, multiple regression analysis showed that Doppler stroke volume reduction was a significant correlate of LV mass reduction (β = 0.108, P < .001) independent of BP, heart rate change, and assigned drug treatment. Conclusions Antihypertensive treatment reduces LV mass and decreases the prevalence of LV hypertrophy and concentric LV remodeling. Additional control of Doppler stroke volume potentiates the effect of BP reduction on LV mass regression independent of the BP reduction per se. (Am Heart J 2002;144:1057-64.)     

Cardiac cachexia is associated with right ventricular failure and liver dysfunction

Background

The mechanisms involved in cardiac cachexia remain poorly understood. We examined the association of right ventricular (RV) and hepatic dysfunction with cardiac cachexia.

Methods

We prospectively enrolled 118 patients with left ventricular ejection fraction (LVEF) ≤ 40%, which were subgrouped as follows: New York Heart Association (NYHA) class II (n = 59), NYHA class III without cachexia (n = 41) and NYHA class III with cachexia (n = 18). All patients underwent blood collection, echocardiography and exercise testing.

Results

Reduced systolic RV function (tricuspid annular plane systolic excursion [TAPSE] ≤ 15 mm), was present in 80% of cachectic patients. When comparing NYHA class II patients vs. non-cachectic and cachectic NYHA class III patients we found a stepwise decrease in systolic RV function (TAPSE 19 [16–23] vs. 16 [13–19] vs. 14 [9–15] mm, respectively; p < 0.001) and an increase in right atrial pressure (RAP; > 10 mm Hg: 6.8 vs. 27.5 vs. 75.0%, respectively; p < 0.001), indicating a higher degree of congestive right HF in cardiac cachexia. Systolic and diastolic function of the left ventricle did not differ between non-cachectic and cachectic patients in NYHA class III. Serum alkaline phosphatase and direct bilirubin correlated with TAPSE and RAP, and were highest in cachectic patients (all p ≤ 0.002), suggesting cholestatic dysfunction due to liver congestion. In multivariable regression analysis, RV dysfunction, cholestatic liver parameters and albumin were independently associated with the presence of cardiac cachexia.

Conclusion

Patients with cardiac cachexia display a more pronounced degree of right HF, cholestatic liver dysfunction and hypoalbuminemia compared to non-cachectic patients of similar LVEF and NYHA class.     

Improvements in blood rheology after cardiac rehabilitation and exercise training in patients with coronary heart disease

Objectives Our purpose was to examine the effect of cardiac rehabilitation and exercise training on blood rheology in patients with coronary heart disease (CHD). Although increased blood and plasma viscosity have been associated with an increased risk of CHD, the effects of cardiac rehabilitation and exercise training on blood rheology in patients with CHD are uncertain. Methods We assessed whole blood effective viscosity (μ), hematocrit standardized blood viscosity (μ₄₅), red blood cell transport efficiency (τ_rbc), and plasma viscosity (PV) in 23 nonsmoking patients with CHD before and after a phase II cardiac rehabilitation and exercise training program. In addition, we compared the group data with the data of a healthy reference group of 10 subjects. Results Patients with CHD had significantly elevated μ (3.35 ± 0.35 cp vs 3.06 ± 0.19 cp, P < .05) and μ₄₅ (3.51 ± 0.29 cp vs 3.12 ± 0.06 cp, P < .001) and reduced τ_rbc (12.7% ± 1.0% · cp^-1 vs 14.2% ± 0.7% · cp^-1, P < .001) compared with healthy subjects. After rehabilitation, patients with CHD had reductions in PV (1.85 ± 0.18 cp vs 1.77 ± 0.11 cp, P < .01) and μ₄₅ (3.58 ± 0.22 cp vs 3.39 ± 0.22 cp, P < .0001) and an increase in τ_rbc (12.4% ± 0.8% · cp^-1 vs 13.2% ± 0.9% · cp^-1, P < .0001). Conclusions Cardiac rehabilitation improves blood rheology in patients with CHD by reducing μ₄₅ and PV and elevating τ_rbc. These improvements may contribute to the increased functional capacity and reduced morbidity and mortality that is associated with participation in cardiac rehabilitation and exercise programs. (Am Heart J 2002;143:349-55.)     

Do transmyocardial and percutaneous laser revascularization induce silent ischemia? An assessment by exercise testing

Background Transmyocardial and percutaneous laser revascularization (TMR, PTMR) may reduce angina and increase exercise tolerance in otherwise untreatable angina patients, although the mechanism is unknown and the placebo effect may be significant. One other proposed mechanism is cardiac denervation leading to silent ischemia. Methods Electrocardiograms obtained during symptom-limited exercise (ETT, modified Bruce protocol) at baseline and 12 months were analyzed (blinded core laboratory) from 182 patients randomized to TMR (n = 92) or medical therapy alone (MED_TMR, n = 90) and 219 patients randomized to PTMR (n = 109) or medical therapy alone (MED_PTMR, n = 110). Results Exercise duration increased 1 year after TMR or PTMR relative to medically treated patients (6.8 ± 3.4 min vs 8.6 ± 3.5 min for TMR; 7.3 ± 3.1 min vs 9.1 ± 3.6 min for PTMR, P < .05). At baseline, 20% of TMR and MED_TMR subjects had ST depression >1.0 mm, >80% had angina during exercise, but only 3% had ST changes without chest pain (silent ischemia). This did not change after TMR. In the PTMR group, more subjects exercised to >1.0 mm ST depression (from 17% to 34%, P < .05), with no change in MED_PTMR, but the proportion with silent ischemia did not change in either group. Conclusion Exercise tolerance improved after TMR and after PTMR. Relative to PTMR, TMR more effectively suppressed pain during exercise and ischemic ST depression. However, neither TMR nor PTMR induced significant silent ischemia. These results suggest that denervation may not be a significant factor contributing to angina relief after these procedures. The contribution of the placebo effect was not determined by these results. (Am Heart J 2002;143:1052-7.)     

Coronary stent implantation in patients older than 75 years of age: clinical profile and initial and long-term (3 years) outcome

Objective The objective of this study was to compare the initial and long-term outcome of elderly and younger patients after coronary stent implantation. Methods The evolutions of 76 patients aged >75 years and of 860 patients aged ≤75 years who underwent consecutive stenting (from June 1991 to June 1997) were compared in a cohort study. Results The elderly patients had lower left ventricular ejection fractions (0.58 ± 0.14 vs 0.61 ± 0.13; P = .03) and more frequently had unstable angina (78.9% vs 55.3%; P <.0001), previous heart failure (10.5% vs 4.9%; P = .03), and multivessel disease (68.4% vs 58.3%; P = .08). After the procedure, the elderly patients showed a higher inhospital mortality rate (6.6% vs 2.4%; P = .03) and myocardial infarction rate (5.3% vs 1.7%; P = .04). The long-term follow-up period (mean, 3.2 ± 1.4 years; median, 3.0 years) showed in the elderly a higher mortality rate (15.4% vs 5.8%; P = .006), a lower rate of repeat revascularization (9.2% vs 19.7%; P = .04), and a similar incidence rate of major adverse cardiac events (27.7% vs 28.2%; P = .93). Multivariate analysis of the elderly group identified female gender (hazard ratio, 2.19; 95% CI, 1.18 to 4.06; P = .012) and presence of multivessel disease (hazard ratio, 2.35; 95% CI, 1.05 to 5.26; P = .037) as independent predictors of further events. Conclusion Patients aged >75 years have a less favorable baseline profile and higher inhospital and 3-year mortality rates. However, the incidence rate of major adverse cardiac events in the long term is acceptable and similar to that of younger patients. (Am Heart J 2002;143:620-6.)     

Urine albumin/creatinine ratio and echocardiographic left ventricular structure and function in hypertensive patients with electrocardiographic left ventricular hypertrophy: the LIFE study. Losartan Intervention for Endpoint Reduction

Background Albuminuria, reflecting systemic microvascular damage, and left ventricular (LV) geometric abnormalities have both been shown to predict increased cardiovascular morbidity and mortality. However, the relationship between these markers of cardiovascular damage has not been evaluated in a large hypertensive population. Methods The urine albumin/creatinine ratio (UACR) and echocardiographic measures of LV structure and function were obtained in 833 patients with stage I to III hypertension and LV hypertrophy determined by electrocardiogram (ECG) (Cornell voltage-duration or Sokolow-Lyon voltage criteria) after 14 days of placebo treatment. Results Patients' mean ages were 66 years, 42% were women, 23% had microalbuminuria, and 5% had macroalbuminuria. Patients with eccentric or concentric LV hypertrophy had higher prevalences of microalbuminuria (average 26%-30% vs 9%, P < .001) and macroalbuminuria (6%-7% vs <1%, P < .001). Furthermore, patients with microalbuminuria and macroalbuminuria had a significantly higher LV mass and lower endocardial and midwall fractional shortening. Patients with abnormal diastolic LV filling parameters had a significantly increased prevalence of microalbuminuria. In univariate analyses, UACR correlated positively to LV mass, systolic blood pressure, age (all P < .001) and pulse pressure/stroke volume and negatively to relative wall thickness (both P < .01) and endocardial (P < .05) and midwall shortening (P < .001) but not to diastolic filling parameters. In multiple regression analysis higher UACR was associated with higher LV mass (β = .169, P < .001) independently of older age (β = .095, P < .01), higher systolic pressure (β = .163), black race (β = .186), and diabetes (β = .241, all P < .001). Conclusions In hypertensive patients with ECG LV hypertrophy, abnormal LV geometry and high LV mass are associated with high UACR independent of age, systolic blood pressure, diabetes, and race, suggesting parallel cardiac and microvascular damage. (Am Heart J 2002;143:319-26.)     

Treatment of acromegaly improves myocardial abnormalities

Background Treatment for acromegaly decreases left ventricular (LV) mass, but it is not clear whether diastolic dysfunction is also reversible. With Doppler echocardiography, before and after effective therapy, we assessed the LV morphology and function of patients with acromegaly who were free of complications. Methods In 15 patients with active acromegaly (age range, 33.4 ± 9.3 years), we compared LV Doppler echocardiographic indices, before and after transsphenoidal surgery or radiotherapy or before and after both procedures, noting a significant drop in plasma levels of growth hormone (<2.0 ng/mL after oral glucose tolerance testing). Patients did not have arterial hypertension, diabetes mellitus, thyroid dysfunction, or coronary artery disease. Occasionally, in this series, patients had no symptoms of heart failure, and patients who underwent treatment with somatostatin analog drugs were not included because they did not have a significant hormonal drop. The follow-up period after hormonal control was 2.7 ± 1.7 years. We also studied 15 healthy control subjects matched for age, sex, and body surface area. Results Patients with acromegaly compared with healthy control subjects had increased LV mass index, relative wall thickness, and deteriorated diastolic function. After therapy, most of the abnormalities improved: LV mass index (104 ± 21 g/m² × 87 ± 21 g/m²; P <.01), LV relative wall thickness (0.40 ± 0.06 × 0.35 ± 0.04; P <.01), proto/telediastolic transmitral peak flow velocity ratio (1.17 ± 0.33 × 1.49 ± 0.34; P <.001), and isovolumetric relaxation period (126 ± 18 ms × 113 ± 13 ms; P <.05). Conclusion Treatment of acromegaly in patients without clinical heart failure improves both LV morphology and diastolic function. Avoidance of progression to more advanced forms of acromegalic cardiomyopathy should be possible. (Am Heart J 2002;143:873-6).     

Effects of cardiac rehabilitation and exercise training on autonomic regulation in patients with coronary artery disease

Background Although cardiovascular rehabilitation and exercise training have substantial benefits in various ischemic heart disease (IHD) risk factors and subsequent prognosis after major IHD events, there is a paucity of information about its effects on autonomic regulation (such as heart rate variability [HRV] and baroreflex gain), particularly considering its arterial and cardiopulmonary components. Methods We studied 40 patients (aged 60 ± 6 y) after major IHD events, including 29 who underwent a comprehensive phase II cardiac rehabilitation and exercise training program and 11 controls who did not attend cardiac rehabilitation. Specifically, we determined whether active training improves prognostic indices of autonomic regulation of the SA node and whether changes in baroreflex gain could be ascribed to the arterial or to the cardiopulmonary component of the overall arterial pressure/heart period baroreflex. Results Only patients with IHD undergoing active rehabilitation demonstrated a significant increase in R-R interval, in its variance, in overall gain of arterial pressure/heart period baroreflex (7.44 ± 1.20 ms/mm Hg to 12.12 ± 1.48 ms/mm Hg, P < .001) and in peak oxygen consumption (Δ = 2.45 mL/kg/min, P < .001). Separate examination of the selective arterial and cardiopulmonary components showed that only the latter increased significantly (6.17 ± 1.09 ms/mm Hg to 10.62 ± 1.56 ms/mm Hg; P < .01). Conclusions Cardiac rehabilitation is associated with significant improvements in autonomic markers of neural regulation of the SA node, such as increases in R-R variance and the gain of the overall spontaneous baroreflex, with specific improvements in the cardiopulmonary component as opposed to the arterial baroreflex component of this system. These improvements may further explain the reduction in morbidity and mortality noted after formal cardiac rehabilitation and exercise training programs. (Am Heart J 2002;143:977-83.)     

Detection of left ventricular enlargement and impaired systolic function with plasma N-terminal pro brain natriuretic peptide concentrations

Background Brain- and N-terminal pro brain natriuretic peptide (NT-proBNP) have been identified as promising markers for heart failure. However, previous studies have revealed that they may hold insufficient diagnostic power for implementation into clinical practice because of a significant overlap in the range of plasma levels between healthy subjects and subjects with heart failure. We hypothesized that imprecision of the reference method (ie, the echocardiographic evaluation of left ventricular [LV] function) may have affected results from those earlier studies. We therefore wanted to investigate the diagnostic potential of NT-proBNP with magnetic resonance imaging as the reference method for the cardiac measurements. Methods Forty-eight patients with stable symptomatic heart failure in New York Heart Association functional classifications II to IV were examined once with blood samples and magnetic resonance imaging along with 20 age-matched and gender-matched healthy control subjects. Results NT-proBNP was associated with LV end-diastolic (r = 0.69; P < .0001) and end-systolic (r = 0.73; P < .0001) volume indices, LV mass index (r = 0.69; P < .0001), and LV ejection fraction (r = −0.75; P < .0001). Receiver operating characteristic curves were calculated for the ability of NT-proBNP to detect LV end-diastolic volume index (>105 mL · m⁻²[cut-off]; sensitivity/specificity, 82%/87%), LV end-systolic volume index (>35 mL · m⁻²; sensitivity/specificity, 86%/86%), LV mass index (>152 g · m⁻²; sensitivity/specificity, 85%/86%), and LV ejection fraction (<58%; sensitivity/specificity, 84%/85%) deviating more than 2 standard deviations from control values. Conclusion NT-proBNP is a powerful marker for LV dimensions and systolic function in patients with heart failure and discriminates well between healthy subjects and subjects with impaired LV systolic function or increased LV dimensions. (Am Heart J 2002;143:923-9.)     

Acute blood pressure response to trandolapril and captopril in patients with left ventricular dysfunction after acute myocardial infarction

Objective Our purpose was to compare the blood pressure response to short-term treatment with captopril or trandolapril in patients with left ventricular (LV) dysfunction after acute myocardial infarction (AMI). Methods A multicenter, randomized, double-blind, double-dummy, parallel group study was performed. Treatment was initiated 3 to 10 days after the onset of symptoms. On day 1, patients received a single dose of captopril 6.25 mg, trandolapril 0.5 mg, or placebo in the morning. Treatment was then titrated upward over the next 5 days. Blood pressure was monitored with an automated device for the first 12 hours after dosing on day 1. Conventional blood pressure measurements were performed throughout the study. Results Of 205 patients treated in the study, 193 patients were evaluated for first-dose effects. In the captopril group, the maximum decrease in blood pressure occurred after 2 hours, and the magnitude of this decrease was significantly greater than in the other 2 groups: 8.8 ± 12/6.3 ± 8 mm Hg (captopril) versus 5.4 ± 10/3.1 ± 8 mm Hg (trandolapril) versus 2.4 ± 9/1.4 ± 7 mm Hg (placebo) (P < .01). In the trandolapril group, the maximum decrease occurred after 7 hours and the magnitude of this effect was similar in all 3 groups: 5.9 ± 11/3.6 ± 8 mm Hg (trandolapril) versus 4.3 ± 10/3.5 ± 8 mm Hg (captopril) versus 3.1 ± 11/2.8 ± 8 mm Hg (placebo) (not significant). Although there was a higher incidence of hypotension on day 1 in the captopril group, the overall incidence of hypotension during the study period was similar in both active treatment groups. Conclusion Because of differences in initial blood pressure response profiles, short-term treatment with trandolapril tended to be better tolerated than captopril in post-AMI patients with LV dysfunction. (Am Heart J 2002;143:313-8.)     

Comparison of dobutamine versus milrinone therapy in hospitalized patients awaiting cardiac transplantation: a prospective,randomized trial

Background The use of dobutamine or milrinone for inotropic support in patients with heart failure awaiting cardiac transplantation is largely arbitrary and based on institutional preference. The costs and effectiveness of these drugs have yet to be compared in a prospective, randomized study. Methods We compared clinical outcomes and costs associated with the use of dobutamine or milrinone in 36 hospitalized patients awaiting cardiac transplantation. Patients were randomly assigned to receive either dobutamine or milrinone at the time of initial hospitalization and were followed until death, transplantation, or placement of mechanical cardiac support (intra-aortic balloon pump or left ventricular assist device). Results Seventeen patients were randomly assigned to receive dobutamine (mean dose 4.1 ± 1.4 μg/kg/min) and 19 patients received milrinone (mean dose 0.39 ± 1.0 μg/kg/min). Therapy lasted 50 ± 46 days for those in the dobutamine group and 63 ± 45 days in the milrinone group. We did not detect differences between the 2 groups in right heart hemodynamics, death, need for additional vasodilator/inotropic therapy, or need for mechanical cardiac support before transplantation. Ventricular arrhythmias requiring increased antiarrhythmic therapy occurred frequently in both groups. Total acquisition cost of milrinone was significantly higher than that of dobutamine ($16,270 ± 1334 vs $380 ± 533 P < .00001). Conclusions Both dobutamine and milrinone can be used successfully as pharmacologic therapy for a bridge to heart transplantation. Despite similar clinical outcomes, treatment with milrinone incurs greater cost. (Am Heart J 2003;145:324-9.)     

Impact of disease activity on left ventricular performance in patients with acromegaly

Background In patients with acromegaly, abnormalities of systolic and diastolic left ventricular (LV) performance, mostly associated with hypertension or LV hypertrophy, have been reported. We used 2-dimensional/Doppler echocardiographic methods and tissue Doppler imaging (TDI) to elucidate the impact of disease activity on LV function in patients with acromegaly. Methods In a prospective study design, 15 patients with active acromegaly (AA group; mean age-adjusted serum insuline-like growth factor-I [IGF-I] level, 420 ± 170 ng/mL, mean growth hormone nadir during 75-g oral glucose load, 12.3 ± 30.1 μg/L), 18 patients with cured (n = 14, mean IGF-I level 205 ± 115 ng/mL, mean growth hormone nadir during glucose load 0.72 ± 0.34 μg/L) or well-controlled (n = 4, normal age-adjusted ranges of IGF-I levels with medication with somatostatin analogues 354 ± 88 ng/mL) acromegaly (CA group), and 24 control subjects (control group) underwent 2-dimensional/Doppler echocardiographic measurements, including assessment of the Tei index (isovolumic contraction time and isovolumic relaxation time divided by ejection time). Systolic and diastolic mitral annular velocities (peak systolic velocity, peak early diastolic velocity [E′], peak late diastolic velocity [A′], E′/A′ ratio) were derived from pulsed TDI. Results No significant differences between study groups were observed with respect to muscle mass and systolic parameters, such as ejection fraction, fractional shortening, and peak systolic velocity. In patients with AA, E′ and the E′/A′ ratio were lower than in control and CA subjects (AA 6.8 ± 1.7 cm/s, control 10.0 ± 1.7 cm/s, CA 9.1± 3.0 cm/s, P < .01 AA vs control, P < .05 AA versus CA, AA 0.68 ± 0.22, control 0.98 ± 0.16, CA 0.89 ± 0.37, P < .01 AA vs control and CA, respectively). In comparison with control subjects and patients with CA, patients with AA had a reduced mitral peak velocity of early/late filling ratio (AA 0.78 ± 0.22 m/s, control 1.12 ± 0.33 m/s, CA 1.11 ± 0.36 m/s, P < .05 AA vs control and CA) and a prolonged deceleration time (AA 223 ± 41 ms, control 188 ± 26 ms, CA 185 ± 25 ms, P < .05 AA vs control and CA). The Tei index was significantly elevated in patients with AA in comparison with control subjects and patients with CA (AA 0.54 ± 0.13, control 0.40 ± 0.09, CA 0.44 ± 0.10, P < .05 AA vs control and CA). No significant differences were observed between control subjects and patients with CA with respect to mitral flow-derived variables, TDI parameters, and the Tei index. Conclusion Disease activity has a significant impact on LV performance in patients with acromegaly. In subjects with active disease, diastolic dysfunction and beginning impairment of overall LV performance are present. In patients with cured/well-controlled disease, systolic and diastolic function appear normal. (Am Heart J 2002;144:538-43.)     

Randomized comparison of cilostazol versus ticlopidine hydrochloride for antiplatelet therapy after coronary stent implantation for prevention of late restenosis

Background Cilostazol is a newly developed antiplatelet drug that has been widely applied for clinical use. Its antiplatelet action appears to be mainly related to inhibition of intracellular phosphodiesterase activity. Recently, cilostazol has been used for antiplatelet therapy after coronary stent implantation. However, its evaluation has not been established yet. Methods This prospective randomized trial was designed to investigate the efficacy of cilostazol for the prevention of late restenosis and acute or subacute stent thrombosis in comparison with ticlopidine hydrochloride. One hundred thirty consecutive patients, scheduled for elective coronary stenting, were randomly assigned to receive oral aspirin (81 mg/day) plus ticlopidine hydrochloride therapy (200 mg/day; group I) or aspirin plus cilostazol therapy (200 mg/day; group II). These medications were started at least 2 days before coronary intervention and continued until follow-up coronary angiography was performed 6 months later. Results Subacute stent thrombosis was observed in 2 patients of group I but in no patients of group II. Major cardiac events were similarly present in both groups. Elevated transaminase levels were observed more frequently in group I than in group II (P < .05). Each of the quantitative coronary angiography variables before and immediately after coronary stenting were similar in both groups. At follow-up angiography, however, late lumen loss (0.69 ± 0.79 mm vs 0.28 ± 0.40 mm; P < .01) and loss index (0.42 ± 0.56 vs 0.16 ± 0.27; P < .01) were smaller in group II than in group I. Restenosis rate (13% vs 31%; P < .05) and target lesion revascularization rate (7% vs 21%; P < .05) were both lower in group II than in group I. Conclusion Aspirin plus cilostazol therapy may be an effective regimen for prevention of not only stent thrombosis but also restenosis. (Am Heart J 2002;144:303-8.)     

Association of anxiety with reduced baroreflex cardiac control in patients after acute myocardial infarction

Background Although depression has been associated with increased mortality in patients after acute myocardial infarction (AMI), little is known about the effects of depression on autonomic nervous system control of heart rate. This study evaluated whether depression is associated with impaired baroreflex sensitivity (BRS) in patients with AMI. Methods Two hundred four hospitalized patients with AMI were evaluated 6 ± 3 (mean ± SD) days after AMI. BRS was assessed using cross-spectral analysis to measure baroreceptor-mediated R-R interval oscillations. Depression was determined using the Diagnostic Interview Schedule, and severity of depressive symptoms was measured with the Beck Depression Inventory. In order to adjust for possible differences in anxiety, we also measured state anxiety using the Spielberger State Anxiety Inventory. Results Depression was not significantly related to BRS. However, anxiety was significantly related to low BRS in multivariate analysis, after the potentially confounding variables of age, blood pressure, and respiratory frequency were controlled for. Comparison of groups with high and low anxiety (on the basis of a median split of state anxiety scores) showed that BRS was reduced by approximately 20% in the patients with the higher anxiety scores (4.7 ± 3.2 ms/mm Hg vs 5.7 ± 3.3 ms/mm Hg, P < .05), after adjustment for differences in age, blood pressure, and respiratory frequency. Conclusions High levels of anxiety, but not depression, are associated with reduced vagal control in patients after AMI. (Am Heart J 2002;143:460-6.)     

Deceleration time of early filling in patients with left ventricular systolic dysfunction: functional and prognostic independent value

Background Although diastolic function parameters have been mentioned as significant predictors of functional capacity and prognosis in patients with left ventricular (LV) systolic dysfunction, it has not been fully elucidated whether they keep an independent predictive value when multiple parameters from a wide variety of examinations are considered. Methods We prospectively studied 60 patients with New York Heart Association (NYHA) class II-IV chronic heart failure symptoms and LV ejection fraction <0.4. At the time of entry into the study, demographic data and functional class were obtained, and usual Doppler echocardiographic, radionuclide ventriculographic, cardiopulmonary exercise testing and hemodynamic variables were determined. Deceleration time of early filling (DT) and NYHA functional class were the only independent predictors of functional capacity as assessed by means of peak oxygen uptake (peak Vo₂). Mean follow-up was 21 ± 6 months, and event-free survival was defined as the absence of cardiac death, urgent cardiac transplantation, or hospital admission requiring inotropic or mechanical support. Results Multivariate Cox analysis showed that DT (P = .008), peak Vo₂ (P = .01), and NYHA class (P = .02) were independent predictors of event-free survival at 1 year. Patients in the lowest tertile of DT (<130 ms) had a significantly lower event-free survival than patients in the intermediate (44% vs 80%, P = .03) and in the highest tertile (44% vs 83%, P = .02). Patients with both a DT <130 milliseconds and a peak Vo₂ <14 mL/kg/min had the highest rate of events at 1 year (83% vs 22% for the remaining patients, relative risk 3.75, P < .001). Conclusions In patients with LV systolic dysfunction, DT is a powerful independent predictor of functional capacity and prognosis among a wide variety of variables. A shortened DT (<130 ms) identifies a subgroup of patients with a worse outcome, especially when combined with a reduced peak Vo₂ (<14 mL/kg/min). (Am Heart J 2002;143:1101-6.)     

Large brachial artery diameter is associated with angiographic coronary artery disease in women

Background Noninvasive methods are needed for the identification of women at highest risk for coronary artery disease (CAD) who might benefit most from aggressive preventive therapy. Identification of brachial artery atherosclerosis, which correlates with coronary artery atherosclerosis, may be useful to estimate or stratify CAD risk. Because atherosclerosis disrupts the arterial architecture that regulates vessel size, we hypothesized that noninvasively measured large brachial artery diameter is a manifestation of atherosclerosis that is associated with angiographic CAD in women with chest pain. Methods We examined 376 women (mean age, 57.1 years) with chest pain in the National Heart, Lung, and Blood Institute's Women's Ischemia Syndrome Evaluation study who underwent B-mode ultrasound scan measurement of brachial artery diameter at rest and during hyperemic stress (to quantify flow-mediated dilation), quantitative coronary angiography, and risk factor assessment. Results Large resting brachial artery diameter was associated with significant angiographic CAD (3.90 ± 0.79 mm vs 3.52 ± 0.59 mm in women with CAD vs no CAD; P < .001). Impaired flow-mediated dilation, which correlated with resting diameter (r = −0.17; P = .001), was weakly associated with significant CAD (2.74% ± 7.11% vs 4.48% ± 9.52% in CAD vs no CAD; P = .046). After adjustment for age, body size, and CAD risk factors, women with large resting brachial artery diameters (>4.1 mm) had 3.6-fold increased odds (95% confidence interval, 1.8 to 7.1; P < .001) of significant angiographic CAD compared with those with small brachial arteries (≤3.6 mm). Conclusion Large resting brachial artery diameter is an independent predictor of significant CAD in women with chest pain. Therefore, a simple ultrasonographic technique may be useful in the identification of women with chest pain who are at increased risk for CAD. (Am Heart J 2002;143:802-7.)     

Effect of cardiac rehabilitation on functional outcomes after coronary revascularization

Background Current guidelines recommending cardiac rehabilitation (CR) after coronary revascularization are largely based on early studies that evaluated only a subset of the population and failed to assess the impact of CR on a patient's perception of their functional status. The main objective of this study was to evaluate the impact of CR in a diverse contemporary population on patient functional outcomes. Methods We studied the effect of CR on 6-month SF-36 Physical Functioning (PF) in 700 patients (mean age 67 ± 11 years, 37% women) who underwent coronary bypass grafting or percutaneous intervention from August 1998 to July 2000. Results Overall CR participation was 24%. At baseline, CR participants had higher PF (mean 62.5 vs 52.5, P < .001). After adjusting for baseline clinical variables and PF score, CR was associated with significant improvement in 6-month PF (+5.0, 95% CI 1.0-9.0). This improvement was observed in all patient subgroups, but tended to be greater in magnitude in men versus women, patients aged <70 years versus ≥70 years, and patients with coronary bypass grafting versus patients with percutaneous intervention. CR participants also tended to be more likely to engage in regular exercise (63% vs 55%, P = .06) and modify their diet (82% vs 73%, P = .07). Rates of rehospitalization and repeat revascularization were similar among CR participants and nonparticipants. Conclusions CR after coronary revascularization is associated with improved functional outcomes and adoption of secondary preventive measures. Innovative strategies to facilitate CR enrollment and tailoring programs to better address the needs of all patient subgroups would extend these benefits to more eligible patients. (Am Heart J 2003;145:445-51.)     

Effects of sibutramine on ventricular dimensions and heart valves in obese patients during weight reduction

Background Obesity enhances hemodynamic alterations that predispose to a subsequent increase in left ventricular (LV) wall stress leading to LV hypertrophy. In obese subjects, weight reduction regresses LV mass (LVM), regardless of blood pressure. Sibutramine can increase blood pressure and heart rate, which may attenuate the reductions in LVM associated with weight loss. Methods Outpatients (n = 184, age 18-65 y, body mass index ≥30 to <40 kg/m²) were randomly assigned to 6 months of once daily double-blind treatment with sibutramine 10 mg or 20 mg, or placebo. LV dimensions, status and function of the valves, weight loss, blood pressure, heart rate, and electrocardiogram were assessed. Results For end point data sets, the mean ± SD LVM index (LVM/height) changes were −3.0 ± 11.9 g/m for placebo (n = 56), −4.4 ± 10.7 g/m for sibutramine 10 mg (n = 61), and −4.3 ± 10.9 g/m for sibutramine 20 mg (n = 56). The reductions observed in the sibutramine groups were statistically significant compared with baseline (P < .01), but pairwise comparison results with placebo were not statistically significant. There was no difference in overall status of the cardiac valves. A statistically significant greater weight loss was found in patients on both doses of sibutramine compared with placebo (P < .001). No statistically significant differences between the groups were observed in respect to blood pressure and electrocardiographic intervals, but a statistically significant increase in pulse rate (7 beats/min) was noted for patients with sibutramine treatment. Conclusion A 6-month treatment with sibutramine does not affect ventricular dimensions, heart valves, and electrocardiogram variables. (Am Heart J 2002;144:508-15.)