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PubMed2003

Prognostic value of the atrial systolic mitral annular motion velocity in patients with left ventricular systolic dysfunction.

BACKGROUND: Transmitral flow velocity variables are powerful predictors of poor prognosis in patients with left ventricular (LV) systolic dysfunction. However, these variables may not accurately reflect the severity of pulmonary congestion. This study was designed to determine whether the peak atrial systolic mitral annular motion velocity (MA-Aw) measured by pulsed Doppler tissue imaging can predict cardiac death or hospitalization for worsening heart failure in patients with LV systolic dysfunction. METHODS: MA-Aw was recorded in 96 patients with LV systolic dysfunction who were followed up for 29 +/- 10 months. All patients underwent Doppler echocardiography on entry into the study, and cardiac catheterization was performed in 45 patients. Patients were divided into 3 groups on the basis of the ratio of early (E) to late (A) diastolic filling (E/A) of the transmitral flow velocity: group 1 (n=31; E/A < 1); group 2 (n=37; 1 < or = E/A < 2); and group 3 (n=28; E/A > or = 2). RESULTS: During follow-up, 36 patients (38%) died of cardiac causes and 34 (35%) were hospitalized for worsening heart failure. There were 2 cardiac deaths (6%) in group 1, 14 (39%) in group 2, and 20 (56%) in group 3. The MA-Aw correlated closely with the mean pulmonary capillary wedge pressure. Univariate Cox model analysis showed that MA-Aw < or = 5 cm/s was the most powerful predictor of cardiac death or hospitalization for worsening heart failure compared with clinical, hemodynamic, and the other echocardiographic variables. Furthermore, MA-Aw < or = 5 cm/s was clearly discernible as a good predictor of cardiac mortality on multivariate Cox model and as assessed by Kaplan-Meier method. CONCLUSION: The MA-Aw obtained by pulsed Doppler tissue imaging is a sensitive index of pulmonary congestion in patients with LV systolic dysfunction. It is a simple and noninvasive outcome measure and can be used to monitor treatment.

Blood Flow Velocity↗
PubMed1999

Effects of calcium-channel blockade in older patients with diabetes and systolic hypertension. Systolic Hypertension in Europe Trial Investigators.

BACKGROUND: Recent reports suggest that calcium-channel blockers may be harmful in patients with diabetes and hypertension. We previously reported that antihypertensive treatment with the calcium-channel blocker nitrendipine reduced the risk of cardiovascular events. In this post hoc analysis, we compared the outcome of treatment with nitrendipine in diabetic and nondiabetic patients. METHODS: After stratification according to center, sex, and presence or absence of previous cardiovascular complications, 4695 patients (age, > or =60 years) with systolic blood pressure of 160 to 219 mm Hg and diastolic pressure below 95 mm Hg were randomly assigned to receive active treatment or placebo. Active treatment consisted of nitrendipine (10 to 40 mg per day) with the possible addition or substitution of enalapril (5 to 20 mg per day) or hydrochlorothiazide (12.5 to 25 mg per day) or both, titrated to reduce the systolic blood pressure by at least 20 mm Hg and to less than 150 mm Hg. In the control group, matching placebo tablets were administered similarly. RESULTS: At randomization, 492 patients (10.5 percent) had diabetes. After a median follow-up of two years, the systolic and diastolic blood pressures in the placebo and active-treatment groups differed by 8.6 and 3.9 mm Hg, respectively, among the diabetic patients. Among the 4203 patients without diabetes, systolic and diastolic pressures differed by 10.3 and 4.5 mm Hg, respectively, in the two groups. After adjustment for possible confounders, active treatment was found to have reduced overall mortality by 55 percent (from 45.1 deaths per 1000 patients to 26.4 deaths per 1000 patients), mortality from cardiovascular disease by 76 percent, all cardiovascular events combined by 69 percent, fatal and nonfatal strokes by 73 percent, and all cardiac events combined by 63 percent in the group of patients with diabetes. Among the nondiabetic patients, active treatment decreased all cardiovascular events combined by 26 percent and fatal and nonfatal strokes by 38 percent. In the group of patients receiving active treatment, reductions in overall mortality, mortality from cardiovascular disease, and all cardiovascular events were significantly larger among the diabetic patients than among the nondiabetic patients (P=0.04, P=0.02, and P=0.01, respectively). CONCLUSIONS: Nitrendipine-based antihypertensive therapy is particularly beneficial in older patients with diabetes and isolated systolic hypertension. Thus, our findings do not support the hypothesis that the use of long-acting calcium-channel blockers may be harmful in diabetic patients.

Aged↗
PubMed2006

Tricuspid annular systolic velocity: a useful measurement in determining right ventricular systolic function regardless of pulmonary artery pressures.

Assessment of right ventricular (RV) systolic function can be somewhat difficult, particularly in pulmonary hypertension (PH). RV fractional area change (FAC) and tricuspid valve annular motion (TAPSE) although useful in the assessment of RV performance, their use can be sometimes limited and tedious. Thus, a quicker but yet reliable alternative is needed. Accordingly, we compared peak tricuspid annulus systolic (TA Sa) velocities derived from Doppler tissue imaging (DTI) with both RVFAC and TAPSE to estimate RV function in 52 patients (53 +/- 16 years) with varying degrees of PH. In this group, mean was RVFAC 49 +/- 20, TAPSE was 2.3 +/- 0.7 cm, peak TA Sa velocity by DTI was 10.4 +/- 3.8 cm/s, left ventricular systolic function was 57 +/- 18%, and pulmonary artery systolic pressure was 47 +/- 28 mmHg. An excellent correlation was noted between TAPSE and RVFAC (r = 0.91, P < 0.001). Similar correlations were noted between peak TA Sa velocity and RVFAC (r = 0.84, P < 0.001) and between peak TA Sa velocity and TAPSE (r = 0.90, P < 0.001). A TA Sa >10.5 cm/s identified individuals with both a normal RV function and without significant PH. Therefore, we conclude that TA Sa velocity, an easily obtainable DTI measure, that has an excellent correlation with more time-consuming methods to assess RV systolic function regardless of the degree of PH should be routinely assessed during the initial evaluation and eventual follow-up of patients either at risk or with documented PH.

Adult↗
PubMed2005

Prognostic value of systolic mitral annular velocity measured with Doppler tissue imaging in patients with chronic heart failure caused by left ventricular systolic dysfunction.

OBJECTIVE: To assess the prognostic value of various conventional and novel echocardiographic indices in patients with chronic heart failure (CHF) caused by left ventricular (LV) systolic dysfunction. METHODS: 185 patients with a mean (SD) age of 67 (11) years with CHF and LV ejection fraction < 45% despite optimal pharmacological treatment were prospectively enrolled. The patients underwent two dimensional echocardiography with tissue harmonic imaging to assess global LV systolic function and obtain volumetric data. Transmitral flow was assessed with conventional pulse wave Doppler. Systolic (Sm), early, and late diastolic mitral annular velocities were measured with the use of colour coded Doppler tissue imaging. RESULTS: During a median follow up of 32 months (range 24-38 months in survivors), 34 patients died and one underwent heart transplantation. Sm velocity (hazard ratio (HR) 0.648, 95% confidence interval (CI) 0.463 to 0.907, p = 0.011), diastolic arterial pressure (HR 0.965, 95% CI 0.938 to 0.993, p = 0.015), serum creatinine (HR 1.006, 95% CI 1.001 to 1.011, p = 0.023), LV ejection fraction (HR 0.945, 95% CI 0.899 to 0.992, p = 0.024), age (HR 1.035, 95% CI 1.000 to 1.071, p = 0.052), LV end systolic volume index (HR 1.009, 95% CI 0.999 to 1.019, p = 0.067), and restrictive pattern of transmitral flow (HR 0.543, 95% CI 0.278 to 1.061, p = 0.074) predicted the outcome of death or transplantation on univariate analysis. On multivariate analysis, only Sm velocity (HR 0.648, 95% CI 0.460 to 0.912, p = 0.013) and diastolic arterial pressure (HR 0.966, 95% CI 0.938 to 0.994, p = 0.016) emerged as independent predictors of outcome. CONCLUSIONS: In patients with CHF and LV systolic dysfunction despite optimal pharmacological treatment, the strongest independent echocardiographic predictor of prognosis was Sm velocity measured with quantitative colour coded Doppler tissue imaging.

Adult↗
PubMed2003

Combined ventricular systolic and arterial stiffening in patients with heart failure and preserved ejection fraction: implications for systolic and diastolic reserve limitations.

BACKGROUND: Heart failure with preserved ejection fraction (HF-nlEF) is common in aged individuals with systolic hypertension and is frequently ascribed to diastolic dysfunction. We hypothesized that such patients also display combined ventricular-systolic and arterial stiffening that can exacerbate blood pressure lability and diastolic dysfunction under stress. METHODS AND RESULTS: Left ventricular pressure-volume relations were measured in patients with HF-nlEF (n=10) and contrasted with asymptomatic age-matched (n=9) and young (n=14) normotensives and age- and blood pressure-matched controls (n=25). End-systolic elastance (stiffness) was higher in patients with HF-nlEF (4.7+/-1.5 mm Hg/mL) than in controls (2.1+/-0.9 mm Hg/mL for normotensives and 3.3+/-1.0 mm Hg/mL for hypertensives; P<0.001). Effective arterial elastance was also higher (2.6+/-0.5 versus 1.9+/-0.5 mm Hg/mL) due to reduced total arterial compliance; the latter inversely correlated with end-systolic elastance (P=0.0001). Body size and stroke volumes were similar and could not explain differences in ventricular-arterial stiffening. HF-nlEF patients also displayed diastolic abnormalities, including higher left ventricular end-diastolic pressures (24.3+/-4.6 versus 12.9+/-5.5 mm Hg), caused by an upward-shifted diastolic pressure-volume curve. However, isovolumic relaxation and the early-to-late filling ratio were similar in age- and blood pressure-matched controls. Ventricular-arterial stiffening amplified stress-induced hypertension, which worsened diastolic function, and predicted higher cardiac energy costs to provide reserve output. CONCLUSION: Patients with HF-lnEF have systolic-ventricular and arterial stiffening beyond that associated with aging and/or hypertension. This may play an important pathophysiological role by exacerbating systemic load interaction with diastolic function, augmenting blood pressure lability, and elevating cardiac metabolic demand under stress.

Adult↗
PubMed1991

Isolated systolic hypertension in the elderly: implications of Systolic Hypertension in the Elderly Program (SHEP) for clinical practice and for the ongoing trials.

The Systolic Hypertension in the Elderly Program (SHEP) was a double-blind placebo-controlled outcome trial on the treatment of isolated systolic hypertension (systolic pressure: 160-219 mmHg and diastolic pressure less than 90 mmHg). From 447, 921 screenes (age greater than or equal to 60 years) 4,736 patients were randomised. A significant reduction of non-fatal stroke (37%), non-fatal myocardial infarction (33%) and left ventricular failure (54%) was observed in the active treatment group. By contrast, the reduction in transient ischaemic attacks (25%), and in total (13%), cardiovascular (20%), cerebrovascular (29%) and coronary (20%) mortality did not reach a level of statistical significance. SHEP is a landmark trial on the treatment of isolated systolic hypertension (ISH) in the elderly. However, the question to what extent the SHEP results can be extrapolated to clinical practice remains open for debate. Indeed, it is possible that due to selection, the SHEP patients were not entirely representative of the elderly with ISH in the population at large. By contrast with previous intervention studies in elderly patients with combined systolic and diastolic hypertension, the SHEP trail did not demonstrate a significant beneficial effect of antihypertensive treatment on any of the cardiovascular mortality endpoints. Confirmation or rejection of the SHEP results in other trials, including the Syst-Eur study, conducted by the rejection of the SHEP results in other trials, including the Syst-Eur study, conducted by the European Working Party on High Blood Pressure in the Elderly and the Chinese trial in elderly ISH patients, is now awaited.

Aged↗
PubMed1989

Variation in end-systolic pressure-diameter relationship using dP/dtmin or P/Dmax as a definition of end-systole in chronic endotoxemic pigs.

We have reported that cardiac inotropism is reduced in various shock states, most recently during chronic endotoxemia (Lee et al.: American Journal of Physiology 254:H324-H330, 1988) [1]. We based this conclusion upon the alterations observed in the slope of the end-systolic pressure-diameter relationship (ESPDR). Recently, Dietrick and Raymond (Dietrick and Raymond: Surgical Infection Society, 7th Annual Meeting, May, 1987, p 83) [2] have reported that the slope of the end-systolic pressure-wall thickness relationship was augmented in the early stages of sepsis and depressed immediately prior to expiration. One major difference between our studies is the definition of end-systole; we used the time when the ratio of pressure-to-diameter (P/D) in the left ventricle is maximal (P/Dmax), whereas they used the time when the first derivative of pressure is minimal (dP/dtmin). In order to determine if the discrepancy between our conclusions could be explained by the differing definitions of end-systole, data from previous studies were reanalyzed, and the slope of the pressure-diameter relationship at P/Dmax and at dP/dtmin was calculated. Pigs were equipped with instruments to measure left ventricular pressure, short axis diameter, and ECG. Observations during the basal state were obtained 3-7 days after surgery. Chronic endotoxemia was induced by intravenous infusion of S. enteriditis endotoxin via an osmotic minipump at 10 micrograms/kg/hr. During the basal state, the value for the slope of ESPDR at dP/dtmin was lower than the value for the slope of ESPDR at P/Dmax, and there was a good correlation between the two values. During chronic endotoxemia, the slope of ESPDR at dP/dtmin did not change. However, the slope of ESPDR at P/Dmax decreased significantly suggesting that chronic endotoxemia reduced cardiac inotropism. This conclusion is supported by the findings that chronic endotoxemia reduced steady-state values of percentage diameter-shortening (an estimate of ejection fraction) and stable stroke work at significantly higher end-diastolic diameter. These data indicate that it is possible to calculate differing slopes of ESPDR from the same observations dependent upon the time during the cardiac cycle chosen as end-systole. More importantly, these data suggest that during chronic endotoxemia, ventricular relaxation dynamics may change so that postsystolic shortening becomes more prominent and therefore higher values for the slope of ESPDR using pressure and diameter values at dP/dtmin can be calculated.

Animals↗
PubMed1987

Effect of right ventricular hypertrophy on cardiac performance and the relation between right ventricular systolic peak pressure and end-systolic volume.

To investigate the role of hypertrophy of the right ventricle upon right heart performance and the significance of the peak systolic pressure/end-systolic volume (P/V) ratio in terms of right ventricular systolic performance, simultaneous measurements of radionuclide ventriculograms and central hemodynamics were done in 32 patients with chronic obstructive pulmonary disease. In 26 of the patients (80%) technically adequate two-dimensional echocardiograms could be performed. In the subset of patients with increased (greater than or equal to 6 mm) right ventricular end-diastolic wall thickness no relationship between pulmonary artery pressure and right ventricular ejection fraction (RVEF) existed in comparison with the remaining patients. P/V indices and cardiac output were not decreased. Considering the patients, whose P/V ratio did not increase from rest to exercise, RVEF decreased highly significantly more than in the remaining patients. The ratio of wall thickness and end-diastolic radius as determinant of peak systolic stress was significantly decreased in these patients compared with the remaining patients. In the patients with right ventricular hypertrophy despite significantly higher values of pulmonary artery pressures and resistances, the afterload in terms of systolic wall stress is markedly reduced. We conclude that in the hypertrophic state, right ventricular performance is not impaired despite decreased RVEF values. In the patients whose P/V ratio does not increase from rest to exercise, an inappropriate high peak systolic wall stress may exist both due to inadequate wall thickness and increased diameter of the right ventricle. The role of P/V in terms of prognosis and development of decompensated right heart failure remains undetermined.

Biomechanical Phenomena↗
PubMed1994

Impact of the treatment of isolated systolic hypertension on behavioral variables. Results from the systolic hypertension in the elderly program.

BACKGROUND: Little information has been published on the impact of antihypertensive medications on quality of life in older persons. Particular concern has existed that lowering systolic blood pressure in older persons might have adverse consequences on cognition, mood, or leisure activities. METHODS: A multicenter double-blind randomized controlled trial was conducted over an average of 5 years' followup involving 16 academic clinical trial clinics. Participants consisted of 4736 persons (1.06%) selected from 447,921 screenees aged 60 years and older. Systolic blood pressure at baseline ranged from 160 to 219 mm Hg, while diastolic blood pressure was less than 90 mm Hg. Participants were randomized to active antihypertensive drug therapy or matching placebo. Active treatment consisted of 12.5 to 25 mg of chlorthalidone for step 1, while step 2 consisted of 25 to 50 mg of atenolol. If atenolol was contraindicated, 0.05 to 0.10 mg of reserpine could be used for the second-step drug. The impact of drug treatment on measures of cognitive, emotional, and physical function and leisure activities was assessed. RESULTS: Our analyses demonstrate that active treatment of isolated systolic hypertension in the Systolic Hypertension in the Elderly Program cohort had no measured negative effects and, for some measures, a slight positive effect on cognitive, physical, and leisure function. The positive findings in favor of the treatment group were small. There was no effect on measures related to emotional state. Measures of cognitive and emotional function were stable in both groups for the duration of the study. Both treatment groups showed a modest trend toward deterioration of some measures of physical and leisure function over the study period. CONCLUSIONS: The overall study cohort exhibited decline over time in activities of daily living, particularly the more strenuous ones, and some decline in certain leisure activities. However, mood, cognitive function, basic self-care, and moderate leisure activity were remarkably stable for both the active and the placebo groups throughout the entire study. Results of this study support the inference that medical treatment of isolated systolic hypertension does not cause deterioration in measures of cognition, emotional state, physical function, or leisure activities.

Activities of Daily Living↗
PubMed1994

A comparison of systolic blood pressure measurement obtained using a pulse oximeter, and direct systolic pressure measurement in anesthetized sows.

Systolic blood pressure measurement obtained with a pulse oximeter has been compared to values obtained by other indirect methods in man. Direct pressure measurement is subject to less error than indirect techniques. This study was designed to compare systolic pressure values obtained using a pulse oximeter, with values obtained by direct arterial pressure measurement. The pulse oximeter waveform was used as an indication of perfusion. A blood pressure cuff was applied proximal to the pulse oximeter probe. The cuff was inflated until the oximeter waveform disappeared, this value was recorded as the systolic pressure at the disappearance of the waveform (SPD). The cuff was inflated to a pressure > 200 mmHg, then gradually deflated until the waveform reappeared, this value was recorded as the systolic pressure at reappearance of the waveform (SPR). The average of the two values, SPD and SPR, was calculated and recorded as SPA. The study was performed in sows (n = 21) undergoing cesarean section under epidural anesthesia and IV sedation. A total of 280 measurements were made of SPD, SPR and SPA. Regression analysis of SPA and direct measurement revealed a correlation coefficient (r) of 0.81. Calculation of mean difference (bias) and standard deviation of the bias (precision) for direct pressure--SPA revealed a value of 1.3 +/- 12.1. When compared with direct measurement, the correlation of this technique was similar to that recorded for other indirect techniques used in small animals. This indicates that this technique would be useful for following systolic pressure trends.(ABSTRACT TRUNCATED AT 250 WORDS)

Anesthesia, Epidural↗
PubMed1996

I/D polymorphism of the angiotensin-converting enzyme gene does not predict isolated systolic or systolic-diastolic hypertension in the elderly.

To determine whether insertion/deletion (I/D) polymorphism (intron 16) of the angiotensin converting-enzyme (ACE) gene is associated with isolated systolic hypertension (ISH: systolic blood pressure (BP) > or = 160, diastolic BP < 90 mm Hg) or systolic-diastolic hypertension (S-D hypertension: diastolic BP > or = 90 +/- systolic BP > or = 160 mm Hg) compared with normotensive controls (systolic BP < 160, diastolic BP < 90 mm Hg), we conducted a case-control study of 733 non-institutionalised, elderly (> or = 60 years) residents of Dubbo, NSW. Individuals were classified as: ISH (n = 167), S-D hypertension (n = 207) and normotensive control (n = 359) with age and sex matching. II, DD and ID genotypes were determined by a nested PCR strategy using DNA extracted from serum. The frequencies of D and I alleles in the control population (0.70 and 0.30 respectively) were not significantly different in the ISH group or the S-D hypertension group (chi 2: 1.7, P = 0.42). After adjustment for several potential confounders, neither genotype nor allele predicted ISH (II vs DD: odds ratio (OR): 1.06, 95% confidence interval (CI): 0.55-2.03; I vs D: 1.09, 0.82-1.46) or S-D hypertension (II vs DD: 1.19, 0.67-2.10; I vs D: 1.16, 0.89-1.52) in this elderly cohort. The I/D polymorphism of the ACE gene is not a marker for either form of hypertension in this large elderly sample.

Aged↗
PubMed1987

Assessment of contractility changes in humans by transoesophageal echocardiography: the peak-systolic pressure end-systolic diameter relationship (PSPESDRS).

The peak-systolic pressure end-systolic diameter relationship (PSPESDRS) was determined in ten healthy subjects under general anaesthesia by using the radial artery pressure tracing (peak-systolic pressure) and transoesophageal 2d-and m-mode echocardiography (left ventricular diameters) without blocking of autonomic reflexes. Left ventricular load was changed by injection of a single intravenous dose of 0.2 mg nitroglycerin (NTG). Linear regression analysis showed a close linear relationship during the pressure decrease between peak-systolic pressures and end-systolic diameters. During infusion of dobutamine 5 micrograms/kg/min there was also a close linear relationship during pressure decrease with increased slope and unchanged Do (D0 = diameter at theoretical pressure zero). Values taken during pressure returning to control level were shifted leftward indicating transient increased contractility. We conclude, that the PSPESDRS can reliably be measured in humans without autonomic blockade during the decrease of arterial pressure after NTG, where reflex changes in inotropy are not yet present. This relationship increases in slope with dobutamine, reflecting the increased contractile state.

Blood Pressure↗
PubMed1975

Radiographic appearance of the thorax in systolic click-late systolic murmur syndrome.

The posteroanterior and lateral chest X-ray films of 64 consecutive patients with an isolated systolic click (55 patients) or a systolic click with a late systolic murmur (9 patients) showed a striking frequency of thoracic skeletal abnormalities. There were 50 female and 14 male subjects. The average age of the female subjects was 36.7 years (range 13 to 67), that of the male subjects 39.7 years (range 17 to 56). Seventy-two percent of the female and 78 percent of the male subjects had an anteroposterior/transverse thoracic ratio less than the mean ratio in a small population. Bony abnormalities such as pectus excavatum, straight thoracic spine and scoliosis occurred alone or in a combination in 31 of the 50 female patients (62 percent) and in 8 of the 14 male patients (57 percent). Overall, 39 of the 64 patients (61 percent) had at least one of the skeletal abnormalities. Scoliosis occurred in 25 subjects (39 percent) and was mild in 19. A "straight back" was found in 15 (23 percent) and pectus excavatum in 7 patients (11 percent). The explanation for these findings is not apparent. Thoracic cage abnormalities should be included as one of the nonauscultatory features of the systolic click-late systolic murmur syndrome.

Adolescent↗
PubMed1982

Scintigraphic prediction of pulmonary arterial systolic pressure by regional right ventricular ejection fraction during the second half of systole.

In 49 patients in whom gated equilibrium ventriculography and cardiac catheterization were performed within a 6 day interval, total and fractional portions of global and regional right ventricular ejection fraction (RVEF) were correlated with pulmonary arterial systolic pressure. Pulmonary arterial systolic pressure was normal (30 mm Hg or less) in 27 patients (Group I) and elevated (31 mm Hg or greater) in 22 patients (Group II). The second-half regional RVEF was 38 +/- 8% (mean +/- standard deviation) with a range of 30 to 54% for Group I and 22 +/- 6% with a range of 13 to 32% for Group II. The difference between the means was statistically significant (p less than 0.001). Use of a second-half regional RVEF of 30% as the criterion of elevated pulmonary arterial systolic pressure resulted in a sensitivity of 0.86 and a specificity of 1.00. A power curve fit in which pulmonary arterial systolic pressure = 10.91 (second-half regional RVEF)-0.87 allowed accurate estimation (r = -0.85) of pulmonary arterial systolic pressure from the second-half regional RVEF. It is concluded that second-half regional RVEF may be used to accurately detect pulmonary arterial hypertension and to estimate its extent.

Adult↗
PubMed1988

Rationale and design of a randomized clinical trial on prevention of stroke in isolated systolic hypertension. The Systolic Hypertension in the Elderly Program (SHEP) Cooperative Research Group.

Isolated systolic hypertension (ISH)--i.e. high systolic pressure with nonhypertensive (less than 90 mmHg) diastolic pressure--is a recognized risk factor for cardiovascular disease among individuals in the age group 60 years and above. This observation suggests that antihypertensive treatment might be beneficial. Results of the Systolic Hypertension in the Elderly Program Pilot Study (SHEP-PS) indicated the feasibility of a full-scale clinical trial on the efficacy of drug treatment of ISH. The Systolic Hypertension in the Elderly Program (SHEP) is a randomized, double-blind, placebo-controlled clinical trial with the primary objective of assessing the effect of drug treatment of ISH--systolic pressure 160-219 mmHg and diastolic pressure less than 90--on occurrence of fatal and nonfatal stroke. This multicenter clinical trial has a sample size of 4736 participants, with high statistical power to detect a reduction of 32% or more in the study's primary end point during the 4-6 year period of treatment and follow-up. Low dosage chlorthalidone is the main study drug. Further features of the design of SHEP and the trial's organization are described.

Aged↗
PubMed1999

Systolic Hypertension in Europe (Syst-Eur) trial phase 2: objectives, protocol, and initial progress. Systolic Hypertension in Europe Investigators.

The Systolic Hypertension in Europe (Syst-Eur) trial proved that blood pressure (BP) lowering therapy starting with nitrendipine reduces the risk of cardiovascular complications in older (> or = 60 years) patients with isolated systolic hypertension (systolic BP > or = 160 mm Hg and diastolic BP < 95 mm Hg). After the completion of the Syst-Eur trial on 14 February 1997, 3506 consenting patients (93.0% of those eligible) were enrolled in phase 2 of the Syst-Eur trial. This open follow-up study aims to confirm the safety of long-term antihypertensive therapy based on a dihydropyridine. To lower the sitting systolic BP below 150 mm Hg (target BP), the first-line agent nitrendipine (10-40 mg/day) may be associated with enalapril (5-20 mg/day), hydrochlorothiazide (12.5-25 mg/day), both add-on study drugs, or if required any other antihypertensive agent. On 1 November 1998, 3248 patients were still being followed, 86 patients had proceeded to non-supervised follow-up, and 43 had died. The median follow-up in Syst-Eur 2 was 14.3 months. At the last available visit, systolic/diastolic BP in the patients formerly randomised to placebo (n = 1682) or active treatment (n = 1824), had decreased by 13.2/5.2 mm Hg and by 4.6/1.6 mm Hg, respectively, so that the between-group BP difference was 1.7 mm Hg systolic (95% Ci: 0.8 to 2.6 mm Hg; P < 0.001) and 0.9 mm Hg diastolic (95% Cl: 0.4 to 1.5 mm mm Hg; P < 0.001). At the beginning of Syst-Eur 2, the goal BP was reached by 25.4% and 50.6% of the former placebo and active-treatment groups; at the last visit these proportions were 55.9% and 63.1%, respectively. At that moment, 45.9% of the patients were on monotherapy with nitrendipine, 29.3% took nitrendipine in combination with other study drugs. Until the end of 2001, BP control of the Syst-Eur 2 patients will be further improved. Cardiovascular complications and adverse events, such as cancer or gastro-intestinal bleeding, will be monitored and validated by blinded experts.

Aged↗
PubMed1976

The determinants of onset of mitral valve prolapse in the systolic click-late systolic murmur syndrome.

The onset of mitral valve prolapse and its close correlate, the time of systolic click, vary considerably with different physiologic and pharmacologic interventions. In order to explain the mechanism responsible for these alterations, the effects of tilt and amyl nitrite inhalation on left ventricular dynamics and the time of the systolic click were studied by analyzing echocardiograms and simultaneously recorded phonocardiograms in 14 patients with mitral valve prolapse and mid-systolic click. The patients were studied in the supine position, with 40-60 degrees head-up tilt and after amyl nitrite inhalation. Computer analysis of the recordings was used to measure the left ventricular end-diastolic diameter, the click diameter (left ventricular diameter at the time of mid-systolic click), the maximal velocity of circumferential fiber shortening (max VCF), and the time interval between the first heart sound and systolic click (S1-X). With tilt and amyl nitrite, shortening of the S1-X interval b y an average of 44 and 87 msec, respectively, was observed. The click diameter, however, remained virtually constant with both maneuvers. Earlier prolapse after tilt was due to a decrease in the end-diastolic diameter from 5.03 +/- 0.74 to 4.50 +/- 0.68 cm (P less than 0.001) with no change in max VCF. Immediately after amyl nitrite, earlier prolapse was due to an increase of VCF in the preprolapse period, with max VCF increasing from 2.15 +/- 0.27 to 3.06 +/- 0.40 circ/sec (P less than 0.001), there being no change in the end-diastolic diameter up to this time. The constant click diameter indicates that the abnormal valve motion in this syndrome occurs at a critical left ventricular chamber size. Variations in the onset of prolapse are caused by changes in left ventricular end-diastolic dimensions and the velocity of circumferential fiber shortening in the preprolapse period.

Adult↗
PubMed1977

Abnormal left ventricular contraction pattern in the systolic click-late systolic murmur syndrome.

A contraction abnormality of the left ventricle has previously been described in patients with systolic click-late systolic murmur syndrome. To determine if the contraction abnormality is present in the preprolapse period, LV dimensions and the instantaneous velocity of circumferential fiber shortening (VCF) were studied in 18 patients with the mitral valve prolapse and 16 normal subjects using computer analysis of echocardiograms. VCF attained its maximum (max VCF) during the preprolapse period an average of 94 msec before the mid-systolic click. Max VCF was significantly reduced in patients with mitral valve prolapse (2.06 vs 2.55 circ/sec in normal subjects, P less than 0.001). Despite the reduction in max VCF, no difference in the extent and percentage of diameter shortening was found between patients and normal subjects. This discrepancy is explained by a sustained rate of mid-to-late systolic diameter shortening in the presence of mitral valve prolapse as manifested by a typical VCF profile (P less than 0.001) and a longer duration of diameter shortening (353 vs 306 msec in normal subjects, P less than 0.01). The decrease of max VCF in patients with mitral valve prolapse suggests a reduction in LV contractility. Since the abnormality is present in the preprolapse period, it is unrelated to a direct mechanical effect of the prolapse itself. Additional fiber shortening in mid-to-late systole indicates that the sudden displacement of the mitral leaflets may have an unloading effect on the left ventricle.

Adult↗