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.)     

Prognostic importance of systolic and diastolic function after acute myocardial infarction

Background Although risk stratification after acute myocardial infarction (AMI) often is focused on systolic left ventricular (LV) function, it appears that a more complete study of ventricular function including assessment of LV filling would be useful. Doppler echocardiography allows assessment of LV filling, and with the use of the Tei index (sum of isovolumic relaxation and contraction times divided by ejection time), a global estimate of ventricular function may be obtained. Therefore, the aim of this study was to determine the prognostic importance of LV systolic, diastolic, and overall LV function in a large consecutive population with AMI.Methods Echocardiography was performed within 6 days of AMI. LV systolic, diastolic, and global function was assessed by means of wall motion index (WMI), mitral flow pattern, and Tei index. The primary end point was all-cause death.Results Of 799 enrolled patients, 197 died during a median follow-up of 34 months. In a multivariate model including WMI and clinical parameters, WMI had important prognostic information. When mitral filling pattern and quartiles of Tei index were added to the model, restrictive filling (mitral deceleration time <140 ms) was associated with a risk ratio of 1.9 (95% CI 1.3-2.7, P < .0001, Tei index values of >0.68/0.56-0.68/0.46-0.55/<0.46 were associated with risks of 4.0 [2.1-6.9]/2.3 [1.5-3.9]/2.1 [1.2-3.6]/1.0, P < .001). In this model, WMI had no prognostic value (P = .18).Conclusions Mitral deceleration time and the Tei index have independent and important prognostic value after AMI. (Am Heart J 2003;145:147-153.)     

Elevated serum uric acid levels are associated with diastolic dysfunction in patients with dilated cardiomyopathy

Objective To assess whether serum uric acid, which is a marker of impaired oxidative metabolism, might correlate with left ventricular systolic and diastolic dysfunction in patients with chronic heart failure (CHF). Background Uric acid levels, which are frequently elevated in patients with CHF, correlate with leg vascular resistance. The effects of elevated levels of uric acid on cardiac function in patients with CHF have never been evaluated. Methods We studied 150 outpatients with CHF who came to our heart failure clinic. Patients underwent a complete echo-Doppler examination, with measurement of mitral E wave and mitral A wave velocities, E/A ratio, E wave deceleration time (DtE), left ventricular volumes, ejection fraction, and stroke volume. A restrictive mitral filling pattern (RMFP) was defined as either E/A ratio >2 or E/A >1 and DtE <140 milliseconds. Results Mean age was 62.2 ± 7.8 years (86% male); 24 patients (16%) had an RMFP. Patients with an RMFP had significantly higher uric acid levels compared with patients without RMFP (0.48 ± 0.14 mmol/L vs 0.38 ± 0.08 mmol/L, respectively, P < .001). Uric acid levels correlated significantly with mitral E wave velocity (r = .22, P < .01), E/A ratio (r = .21, P < .05), DtE (r = .26, P < .01), and RMFP (P = .0001). There was no correlation between uric acid and left ventricular volumes, ejection fraction, or stroke volume. In a multivariate model, uric acid predicted DtE independently of renal function, diuretic dose, and left ventricular volumes. Conclusion Elevated uric acid levels are associated with diastolic dysfunction in CHF. Xanthine oxydase inhibition in patients with CHF might theoretically result in an improvement of diastolic function. (Am Heart J 2002;143:1107-11.)     

Peripheral endothelium-dependent flow-mediated vasodilatation is associated with left ventricular mass in older persons with hypertension

Background Increased left ventricular (LV) mass is associated with greater cardiovascular disease risk. Recent studies have also shown an association of increased LV mass with attenuated endothelium-dependent coronary flow reserve. Less is known about the association between LV mass and endothelium-dependent flow-mediated dilatation (FMD) in peripheral arteries, a noninvasive measure of endothelial function. Methods Sixty-two subjects with untreated mild hypertension, aged 55 to 75 years and otherwise healthy, were examined. Resting blood pressure was obtained by the average of 4 to 5 visits, each at least 1 week apart. LV mass was determined from magnetic resonance imaging and was indexed by body surface area, height and height^2.7. Body composition was assessed with dual energy x-ray absorptiometry. FMD was measured as the percent change of brachial artery diameter during reactive hyperemia by use of high-resolution ultrasound. Results Median LV mass index was 63 g/m² (interquartile range, 58-73). In bivariate analysis, LV mass was correlated to lean body mass (r = 0.63, P < .001), diastolic blood pressure (r = 0.35, P < .01), and FMD (r = −0.27, P < .05). In multivariate analysis, 44% of the variance in log-LV mass was explained by lean body mass. An additional 6% of the variance was explained by FMD (P < .05). For each 1% point decrease in FMD, LV mass increased by 1.1%. Conclusions In addition to the expected influences of body size, impairment of brachial artery FMD was independently related to LV mass in elderly subjects with mild hypertension who did not yet have LV hypertrophy. Whether mild hypertension is the common mechanism linking LV mass and endothelial function has yet to be determined. (Am Heart J 2002;144:39-44.)     

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.)     

Echocardiography-derived variables predict outcome in patients with nonischemic dilated cardiomyopathy with or without a restrictive filling pattern

Background Despite recent therapeutic advances, patients with heart failure caused by dilated cardiomyopathy (DCM) still have high morbidity and mortality rates. In this study, we sought to assess the prognostic value of echocardiographic variables in patients with DCM and to assess the impact of a restrictive left ventricle filling pattern. Design We conducted a retrospective cohort study of 337 patients with DCM, using the Royal Brompton Hospital Echocardiography database for the years 1994 to 1998. Methods and Results There were 337 patients with a mean age of 53 ± 15 years. One hundred ninety-five patients (58%) had a restrictive left ventricle filling pattern (RFP). There was a total of 74 deaths (22%) during the follow-up period (43 ± 25 months). RFP more than tripled the risk of death (adjusted hazard ratio 3.2, 95% CI 1.8-5.7, P = .003). RFP is correlated with isovolumic relaxation time, incoordinate wall-motion, amplitude of right ventricular long axis excursion on M-mode echocardiography, and mitral regurgitation. Conclusion RFP is a powerful independent predictor of mortality in patients with nonischemic DCM. The risk associated with RFP is greatest among patients who had short isovolumic relaxation time, mitral regurgitation, incoordinate wall-motion, and depressed amplitude of right ventricular long axis excursion. Thus, echocardiography-derived variables may stratify patients with heart failure with DCM who are at high risk, for whom aggressive medical treatment or heart transplantation should be considered early. (Am Heart J 2002;144:343-50.)     

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.)     

Relation of impaired left ventricular filling to systolic midwall mechanics in hypertensive patients with normal left ventricular systolic chamber function: the Losartan Intervention for Endpoint Reduction in Hypertension (LIFE) study

Background

Patients with hypertensive left ventricular (LV) hypertrophy commonly have diastolic dysfunction with preserved LV ejection fraction. LV systolic midwall shortening (MWS) may be impaired in hypertensive patients with normal LV ejection fraction. However, it is unclear whether impaired LV filling is related to depressed systolic midwall mechanics.

Methods

Echocardiographic measures of LV diastolic filling and systolic performance were compared in 632 unmedicated patients with stage II or III hypertension and LV hypertrophy determined by electrocardiogram, with LV ejection fraction >55% and <2+ mitral regurgitation.

Results

Stress-corrected LV MWS, an index of myocardial contractility, was lower in patients with abnormal as opposed to normal LV filling patterns (98% ± 12% vs 102% ± 10%, P < .001) and in patients with prolonged as opposed to normal isovolumic relaxation time (IVRT) (98% ± 13% vs 101% ± 12%, P = .014). Stress-corrected MWS was <85% of predicted levels in more patients with abnormal LV filling patterns (11.8% vs 6.3%) or with long IVRT (≥105 msec) (34% vs 21%, both P < .05). In regression analyses, lower stress-corrected MWS and higher LV mass were independent correlates of longer IVRT, while lower stress-corrected MWS was the only independent correlate of prolonged mitral valve deceleration time (P = .017). Higher LV mass had strong, statistically independent relationships to longer IVRT (by 0.3 g/msec) and decreased stress-corrected MWS (by 0.5 g/%; both P < .0001), independent of body size and age.

Conclusion

In patients with moderate hypertension and target organ damage who have normal LV ejection fraction, impaired early diastolic LV relaxation (abnormal E/A ratio, prolonged IVRT and deceleration time) is associated with impaired LV systolic midwall mechanics independent of higher LV mass.     

Immunoglobulin G3 cardiac myosin autoantibodies correlate with left ventricular dysfunction in patients with dilated cardiomyopathy: immunoglobulin G3 and clinical correlates

Background Effector functions of an aberrant immune response have been implicated in the pathogenesis of idiopathic dilated cardiomyopathy (DCM). The immunologic determinants of myocardial dysfunction, however, remain poorly understood. This study sought to determine the relation of different immunologic responses to hemodynamic dysfunction in DCM. Methods Immunoglobulin (Ig) G class/subclass response ELISA (enzyme-linked immunosorbent assay) against cardiac myosin heavy chain, histologic characteristics (DALLAS criteria), immunohistochemistry, plasma interleukin-4 and plasma interferon gamma (IFN-γ) were determined in patients (n = 76) with clinically suspected myocarditis or DCM. Patients were prospectively evaluated, both clinically and hemodynamically, on admission (baseline) and at 6-month follow-up. Results Indices of hemodynamic dysfunction (by cardiac catheterization and transthoracic echocardiography) correlated significantly with an Ig subclass response. IgG3 levels correlated with left ventricular ejection fraction (P = .02), pulmonary capillary wedge pressure (P < .0001), left ventricular end-systolic volume index (P = .002), left ventricular end-diastolic volume index (P = .033), left ventricular end-diastolic pressure (P = .04), right ventricular end-diastolic pressure (P = .039), and left ventricular end-systolic dimension and left ventricular end-diastolic dimension (P < .05). Patients positive for IgG3 (predominantly male, P = .01) had depressed left ventricular ejection fraction (≤45%, relative risk 3.0, 95% CI 1.5-5.7, P = .005) at baseline and 6 months. Mitral-septal separation at follow-up improved in patients negative for IgG3 (P = .018), and the number of patients on conventional therapy in this group declined at 6-month follow-up (P < .05). Lymphocyte counts/high-power field; CD2, CD3, CD4, and CD8 (independent of IgG class/subclass response and left ventricular dysfunction) were significantly higher in patients positive for IFN-γ (25%). A positive IFN-γ response was higher in patients positive for IgG3. These patients, positive for IgG3 and IFN-γ (10%), had significantly shorter duration of clinical symptoms: 0.17 years (0.12-2.36 y) versus 1.01 years (0.49-5.35 y, P = .04). Conclusion IgG3 reactivity correlated with depressed myocardial dysfunction. This may render this subclass Ig a surrogate target for therapeutic intervention in DCM. With IFN-γ, IgG3 may reflect a more aggressive disease. (Am Heart J 2002;143:1076-84.)     

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.)     

Left ventricular remodeling in the first year after acute myocardial infarction and the predictive value of N-terminal pro brain natriuretic peptide

Background Left ventricular (LV) remodeling after myocardial infarction (MI) has received much attention because of its severe impact on morbidity and mortality rates. However, the incidence and extent of LV remodeling in a modern infarct population who were offered antiremodeling treatment in compliance with daily clinical practice is unknown. The purpose of this study was to clarify this issue and to evaluate the predictive value of N-terminal pro brain natriuretic peptide (NT-proBNP). Methods Forty-two patients with a first transmural MI were examined after 1 week, 1 month, 3 months, 6 months, and 1 year with blood samples and magnetic resonance imaging. Results In 12 patients (29%), LV end-diastolic volume index (LVEDVI) and LV end-systolic volume index (LVESVI) increased by 24% and 22% (P <.0001; P = .01). In 12 patients (29%), LVEDVI and LVESVI decreased by 19% and 23% (P <.0001; P = .0005), whereas the remaining 18 patients (43%) had stable conditions regarding these LV measures. LV ejection fraction at baseline was significantly reduced in all patient categories but was unchanged over time. Elevated NT-proBNP level at baseline was identified as an independent predictor of increase in LVEDVI during follow-up examination (P = .007). A baseline level of NT-proBNP >115 pmol/L identified patients who later had LV dilatation develop with a sensitivity and specificity of 89% and 68% (area under curve = 0.77). Conclusion In this 1-year follow-up study of patients with a first transmural MI, approximately 30% had significant increments develop in LVEDVI and LVESVI, and LV ejection fraction remained unchanged. Patients in whom LV dilatation developed could be identified early after the MI with elevated plasma levels of NT-proBNP. (Am Heart J 2002;143:696-702.)     

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).     

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.)     

Increased Atrial Contribution to Left Ventricular Filling Compensates for Impaired Early Filling During Exercise in Heart Failure With Preserved Ejection Fraction

BackgroundThe role of left atrial (LA) function on exercise remains poorly understood in heart failure with preserved ejection fraction (HfpEF) despite its key role in optimizing left ventricular (LV) diastolic function. We used resting and exercise radionuclide ventriculography to investigate the role of LA function in the pathophysiology of HfpEF.Methods and ResultsA total of 25 patients with HfpEF and 15 age- and gender-matched controls were recruited. All subjects underwent resting echocardiogram, metabolic exercise testing to peak effort, and radionuclide ventriculography (at rest and exercise [to 35% of heart rate reserve]). At rest LA and LV function were similar in patients and controls. During exercise, HfpEF patients had lower left ventricular ejection fraction (69 ± 9% vs. 73 ± 10%, P < .05) and lower peak early filling rate (387 ± 109 end-diastolic count/sec vs. 561 ± 156 end-diastolic count/sec, P < .001). During exercise, the atrial contribution to LV filling was significantly higher in patients than controls (46 ± 11% vs. 30 ± 9%, P < .001). Atrial contribution to LV filling correlated negatively with peak early filling rate during exercise (r = -0.6, P < .001). Peak early filling rate correlated positively with peak oxygen consumption (r = 0.485, P = .004) and negatively with minute/carbon dioxide production (r = -0.423, P = .013).ConclusionPatients with HfpEF have increased atrial contribution to LV filling as a compensatory response to impaired early LV filling during cycle exercise.     

Is cardiovascular remodeling in patients with essential hypertension related to more than high blood pressure? A LIFE substudy. Losartan Intervention For Endpoint-Reduction in Hypertension

Background Blocking the renin-aldosterone-angiotensin II system has been hypothesized to induce blood pressure-dependent as well as blood pressure-independent regression of cardiovascular hypertrophy. However, the relative influence of elevated blood pressure (BP) and various neurohormonal factors on cardiovascular remodeling in hypertension is unclear. Methods In 43 untreated patients with hypertension with electrocardiographic left ventricular hypertrophy, we measured relative wall thickness and left ventricular mass index by echocardiography and by magnetic resonance imaging (n = 32), intima-media cross-sectional area, and distensibility of the common carotid arteries by ultrasound, media/lumen ratio of isolated subcutaneous resistance arteries by myography, and median 24-hour systolic BP (n = 40), serum insulin, and plasma levels of epinephrine, norepinephrine, renin, angiotensin II, aldosterone, and endothelin. Results In multiple regression analyses, left ventricular mass index by echocardiography (R² = 0.14, P < .05) and by magnetic resonance imaging (R² = 0.32, P = .001) were associated with 24-hour systolic BP, whereas relative wall thickness was associated with plasma epinephrine (R² = 0.12, P < .05) and aldosterone (R² = 0.10, P < .05). Intima-media cross-sectional area/height was associated with 24-hour systolic BP (β = 0.40) and plasma epinephrine (β = 0.43) (adjusted R² = 0.32, P < .001), whereas carotid distensibility was associated with 24-hour systolic BP (β = 0.40) and plasma angiotensin II (β = −0.41) (adjusted R² = 0.30, P < .001). Media/lumen ratio in subcutaneous resistance arteries was associated with plasma epinephrine (R² = 0.22, P < .01). Conclusion Apart from being associated with a high BP burden, cardiovascular remodeling was associated with high levels of circulating epinephrine, aldosterone, as well as angiotensin II, suggesting a beneficial effect above and beyond the effect of BP reduction when using antihypertensive agents blocking the receptors of these neurohormonal factors. (Am Heart J 2002;144:530-7.)     

Effects of sildenafil citrate (viagra) on cardiac repolarization and on autonomic control in subjects with chronic heart failure

Background Cases of sudden death associated with sildenafil citrate use have been reported in men with coronary artery disease. The aim of this study was to investigate the drug's effect on cardiac repolarization and sinus autonomic and vascular control in men with mild chronic heart failure (CHF; New York Heart Association classification II). Changes in these variables could predispose patients to malignant ventricular arrhythmias. Method We measured QT dispersion, the QT-RR slope, and the index of QT variability (QTVI) and analyzed spectral power of RR and systolic blood pressure variability in 10 men with dilated cardiomyopathy and in 10 control subjects after administration of a single 50-mg oral dose of sildenafil citrate or placebo at rest (not followed with any attempt at intercourse). Results In both groups, oral sildenafil citrate decreased the systolic blood pressure (P <.05) and increased the heart rate (P <.05). In subjects with CHF, it also increased the QT-RR (P <.001) and QTVI (from −0.45 ± 0.07 to −0.27 ± 0.07; P <.001), but in controls, it increased the QTVI (from −1.20 ± 0.08 to −0.78 ± .014; P < .001). In these subjects and controls, oral sildenafil citrate induced a significant reduction in high frequency, expressed in absolute power (subjects with CHF: from 4.04 ± 0.14 to 3.43 ± 0.16 natural logarithm ms²; P <.001; controls: from 5.61 ± 0.44 to 4.98 ± 0.32 natural logarithm ms²; P <.05) and in normalized units (P <.05). In subjects with CHF but not in controls, it also significantly increased the low frequency to high frequency ratio (from 1.3 ± 0.12 to 1.89 ± 0.16; P <.001) and low frequency expressed in normalized units (P <.05).Sildenafil citrate caused no significant changes in the QT interval or dispersion. Conclusion These findings indicate that, in men with heart failure, sildenafil citrate reduces vagal modulation and increases sympathetic modulation, probably through its reflex vasodilatory action. The autonomic system changes induced with sildenafil citrate could alter QT dynamics. Both changes could favor the onset of lethal ventricular arrhythmias. At the dose usually taken for erectile dysfunction, sildenafil citrate has no direct effect on cardiac repolarization (QT interval or dispersion). (Am Heart J 2002;143:703-10.)     

Associations between angiotensinogen gene variants and left ventricular mass and function in the HyperGEN study

Background The angiotensinogen M235T polymorphism is positively associated with plasma angiotensinogen, hypertension, and coronary heart disease. However, the association of M235T polymorphism with left ventricular (LV) mass and function is not well defined at the population level. We investigated whether 2 tightly linked polymorphisms of angiotensinogen gene, M235T and G-6A, are associated with LV mass and function in a large population-based sample, composed mostly of patients with hypertension. Methods Two-dimensional guided M-mode and pulsed Doppler scan echocardiograms were performed in 605 participants. The angiotensinogen M235T was analyzed with a standard polymerase chain reaction test, and the G-6A variant was measured with mass spectrophotometry. Results The association of angiotensinogen gene to LV mass and LV mass indexed to body surface area (LVMI) differed significantly between subjects with normotensive and hypertensive conditions with respect to the direction of association (P < .005). The methionine-threonine/threonine-threonine genotype was negatively associated with LV mass and LVMI in patients with hypertension after adjustment for blood pressure, antihypertensive medication use, weight, and other covariates (P < .001), and patients with normotensive conditions with the methionine-threonine/threonine-threonine genotype had higher LV mass and LVMI (P = .04, for LV mass; P = .14, for LVMI). The association in patients with normotensive conditions was not influenced by blood pressure but was partly confounded by weight. Conclusion Variation in the angiotensinogen gene was modestly associated with LV mass independently of covariates in patients with hypertensive conditions. The direction of the association was opposite to that observed in patients with normotensive conditions, probably because of the influence of other risk factors or antihypertensive medication use or both. (Am Heart J 2002;143:854-60.)     

Plasma Insulin-like Growth Factor 1 Distribution and Its Relation to Blood Pressure in Adolescents: The Bogalusa Heart Study

The distribution of circulating insulin-like growth factor-1 (IGF-1) and its relationship to blood pressure was examined in a community study of 1073 biracial (black–white) adolescents aged 11 to 18 years. Girls of both races displayed higher levels of plasma IGF-1 than did their male counterparts (P < .01), independent of age and sexual maturation. In boys, IGF-1 was correlated positively with height (r = 0.37 P < .001), weight (r = 0.26, P < .001), Tanner stage (r = 0.31, P < .001), and age (r = 0.11, P < .05). Girls, on the other hand, showed an inverse association with age (r = −0.38, P < .001) and Tanner stage (r = −0.10, P < .05). Plasma IGF-1 was correlated positively with systolic blood pressure in boys of both races (r = 0.21 to 0.25, P < .01) and with diastolic blood pressure in white boys (r = 0.18, P < .05), but not in girls of either race. Boys with elevated levels of IGF-1 (>80th percentile) showed significantly higher blood pressure levels, especially during early to middle stages of puberty. Multivariate analysis revealed that IGF-1 was associated with systolic and diastolic blood pressure, independent of age, race, sexual maturation, height, weight, and insulin in boys. These results suggest that plasma IGF-1 may contribute to the regulation of blood pressure only in males during puberty.     

Effects of losartan and captopril on left ventricular systolic and diastolic function after acute myocardial infarction: results of the Optimal Trial in Myocardial Infarction with Angiotensin II Antagonist Losartan (OPTIMAAL) echocardiographic substudy

Background

Angiotensin-converting enzyme inhibitors have been shown to attenuate adverse remodeling after acute myocardial infarction (AMI), and the same has been suggested for angiotensin II type 1 receptor antagonists in animal models. Therefore the aim of the study was to compare the effects of losartan and captopril on regional systolic, diastolic, and overall left ventricular (LV) function after AMI.

Methods

Two hundred twenty-five patients aged ≥50 years with documented AMI and heart failure and/or LV dysfunction were randomly assigned treatment with either losartan (50 mg/d) or captopril (50 mg 3 times/d). Echocardiography was performed at randomization and after 3 months; echocardiograms were analyzed blinded at the core laboratory. Main outcome measures were changes in wall motion score index (WMSI), E-wave deceleration time (E-DT), and Tei index of overall LV function.

Results

WMSI decreased in both groups (losartan 1.58 ± 0.23 to 1.52 ± 0.26, P = .009, captopril 1.60 ± 0.24 to 1.48 ± 0.22, P < .001), although the decrease was greater in patients allocated to captopril (captopril −0.12 ± 0.17 vs losartan −0.05 ± 0.19, P = .007). In both groups E-DT increased, although the increase was significant only in patients treated with captoril (193 ± 61 ms to 208 ± 70 ms, P = .05). The change in E-DT was not different between treatment groups (captopril 14 ± 74 ms vs losartan 7 ± 80 ms, P = .52). Tei index decreased in both groups (losartan 0.59 ± 0.13 to 0.55 ± 0.15, P = .04, captopril 0.62 ± 0.15 to 0.55 ± 0.13, P < .001). However, the reduction was significantly greater in patients treated with captopril (captopril −0.08 ± 0.14 vs losartan −0.03 ± 0.14, P = .01).

Conclusion

Losartan and captopril improve systolic and overall LV function after AMI, but the benefit is greater for patients treated with captopril.     

Tissue Doppler imaging in patients with moderate to severe aortic valve stenosis: clinical usefulness and diagnostic accuracy

Background

Mitral annular velocities derived from tissue Doppler imaging (TDI) provide information about left ventricular (LV) long-axis function and allow for the assessment of LV filling pressures in selected subsets of patients. It was the aim of this study to assess the usefulness of TDI in patients with moderate to severe aortic valve stenosis (AS).

Methods

Twenty-three patients with moderate to severe AS (mean aortic valve area 0.8 ± 0.4 cm²), in whom coronary artery disease had been ruled out, and 36 asymptomatic age-matched control subjects underwent assessment of ejection fraction, fractional shortening, and mitral inflow (E, A, E/A ratio). TDI velocities (S', E', A') were derived from the septal mitral annulus. In patients with AS, LV pressure before atrial contraction (LV pre-A pressure), LV end-diastolic pressure, and cardiac index were measured during cardiac catheterization.

Results

In patients with AS, systolic (S') and early diastolic mitral annular velocities (E') were significantly reduced in comparison to control subjects (systolic, 5.5 ± 1.2 vs 8.3 ± 1.3 cm/s; early diastolic, 5.6 ± 1.6 vs 10.2 ± 3.0 cm/s, P < .001 for both comparisons), but ejection fraction, fractional shortening, and cardiac index were normal. In patients with AS, LV pre-A pressures (14 ± 4 mm Hg) and end-diastolic pressures were high (19 ± 7 mm Hg). In such patients, the mitral E/E' ratio was significantly related to LV pre-A pressure (r = 0.75, P < .001) and to LV end-diastolic pressure (r = 0.78, P < .001). In patients with AS, an E/E' ratio ≥13 identified an LV end-diastolic pressure >15 mm Hg, with a sensitivity of 93% and a specificity of 88%.

Conclusions

In patients with moderate to severe AS, TDI allows for a reliable, noninvasive estimation of filling pressures. In such patients, systolic long-axis function is impaired even in the presence of normal ejection fraction and cardiac index. Thus, TDI integrates information about systolic and diastolic performance and may be a useful addition in the echocardiographic workup and care of patients with AS.