Recent computational studies of the circulatory system in heart failure patients with preserved ejection fraction (HFpEF) suggest that expansion of the stressed blood volume (SBV) is a key contributor to the pathognomonic exaggerated rise in filling pressures during physical activity. The SBV refers to the notional inflexion point above which a portion of the total blood volume contributes to the circulatory filling pressure. We aimed to formally assess venous compliance in HFpEF patients and its relationship to central haemodynamics. Subjects with HFpEF (n=25) and healthy control volunteers (n=12) underwent a formal assessment of venous compliance using simultaneous measurement of intravenous pressures and forearm volume using strain-gauge plethysmography during stepwise increases in venous occlusion. HFpEF patients also underwent invasive haemodynamic assessment at rest and during exercise. Compared to controls, HFpEF patients had markedly reduced venous compliance (0.0303±0.007 vs 0.0456±0.009 %/mmHg, p<0.001) and age was independently, inversely correlated with compliance (r= -0.36, p=0.026). In HFpEF patients, venous compliance was positively correlated with the peak exercise pulmonary capillary wedge pressure (r= 0.47, p=0.017) and right atrial pressure (r= 0.49, p=0.015). These data demonstrate the presence of increased venous stiffness in HFpEF patients compared to healthy subjects. Within HFpEF patients a relatively less compliant venous circulation appears to contribute to the pathognomonic rise in exercise filling and hence may be a contributing factor to their clinical presentation.

BACKGROUNDHypertension leads to cardiac structural and functional changes, commonly assessed by echocardiography. In this study, we assessed the predictive performance of different echocardiographic parameters including left ventricular hypertrophy (LVH) on future cardiovascular outcomes in elderly hypertensive patients without heart failure.METHODSData from LVH substudy of the Second Australian National Blood Pressure trial were used. Echocardiograms were performed at entry into the study. Cardiovascular outcomes were identified over short term (median 4.2 years) and long term (median 10.9 years). LVH was defined using threshold values of LV mass (LVM) indexed to either body surface area (BSA) or height(2.7): >115/95g/m(2) (LVH-BSA(115/95)) or ≥49/45g/m(2.7) (LVH-ht(49/45)) in males/females, respectively, and ≥125g/m(2) (LVH-BSA(125)) or ≥51g/m(2.7) (LVH-ht(51)) for both sexes.RESULTSIn the 666 participants aged ≥65 years in this analysis, LVH prevalence at baseline was 33%-70% depending on definition; and after adjusting for potential risk factors, only LVH-BSA(115/95) predicted both short- and long-term cardiovascular outcomes. Participants having LVH-BSA(115/95) (69%) at baseline had twice the risk of having any first cardiovascular event over the short term (hazard ratio, 95% confidence interval: 2.00, 1.12-3.57, P = 0.02) and any fatal cardiovascular events (2.11, 1.21-3.68, P = 0.01) over the longer term. Among other echocardiographic parameters, LVM and LVM indexed to either BSA or height(2.7) predicted cardiovascular events over both short and longer term.CONCLUSIONSIn elderly treated hypertensive patients without heart failure, determining LVH by echocardiography is highly dependent on the methodology adopted. LVH-BSA(115/95) is a reliable predictor of future cardiovascular outcomes in the elderly.

This study was performed to determine the relative contributions of plasma norepinephrine clearance and norepinephrine release to the increase in plasma norepinephrine concentration that occurs during exercise and to determine whether the high rates of cardiac norepinephrine release from the heart and kidney in patients with heart failure are associated with diminished reserve for regional sympathetic nervous stimulation. During supine steady-state bicycle exercise at 50% of maximum voluntary exercise capacity, the plasma norepinephrine concentration of six patients with congestive heart failure rose from 385±88 to 2,200±497 pg/ml, whereas that of nine normal subjects rose from 208±21 to 882±257 pg/ml. The change in plasma concentration in both groups was due to an increase in norepinephrine spillover to plasma without a change in plasma norepinephrine clearance. In patients with heart failure, cardiac spillover increased from 80 ± 26 to 528 ± 265 ng/min during exercise, and renal spillover

BACKGROUND:Treatment of hypertension with diuretics, beta-blockers, or both leads to improved outcomes. It has been postulated that agents that inhibit the renin-angiotensin system confer benefit beyond the reduction of blood pressure alone. We compared the outcomes in older subjects with hypertension who were treated with angiotensin-converting-enzyme (ACE) inhibitors with the outcomes in those treated with diuretic agents.METHODS:We conducted a prospective, randomized, open-label study with blinded assessment of end points in 6083 subjects with hypertension who were 65 to 84 years of age and received health care at 1594 family practices. Subjects were followed for a median of 4.1 years, and the total numbers of cardiovascular events in the two treatment groups were compared with the use of multivariate proportional-hazards models.RESULTS:At base line, the treatment groups were well matched in terms of age, sex, and blood pressure. By the end of the study, blood pressure had decreased to a similar extent in both groups (a decrease of 26/12 mm Hg). There were 695 cardiovascular events or deaths from any cause in the ACE-inhibitor group (56.1 per 1000 patient-years) and 736 cardiovascular events or deaths from any cause in the diuretic group (59.8 per 1000 patient-years; the hazard ratio for a cardiovascular event or death with ACE-inhibitor treatment was 0.89 [95 percent confidence interval, 0.79 to 1.00]; P=0.05). Among male subjects, the hazard ratio was 0.83 (95 percent confidence interval, 0.71 to 0.97; P=0.02); among female subjects, the hazard ratio was 1.00 (95 percent confidence interval, 0.83 to 1.21; P=0.98); the P value for the interaction between sex and treatment-group assignment was 0.15. The rates of nonfatal cardiovascular events and myocardial infarctions decreased with ACE-inhibitor treatment, whereas a similar number of strokes occurred in each group (although there were more fatal strokes in the ACE-inhibitor group).CONCLUSIONS:Initiation of antihypertensive treatment involving ACE inhibitors in older subjects, particularly men, appears to lead to better outcomes than treatment with diuretic agents, despite similar reductions of blood pressure.

Objective: To test the usage of serial echocardiography in mice with induced myocardial infarct (MI) and to characterize the mouse model of MI. Methods: C57 mice underwent open-chest surgery to induce left coronary artery occlusion or sham-operation (SH). Echocardiography was performed before and at 1, 2.5, 6 and 9 weeks after surgery. Left ventricular end diastolic and end systolic dimensions (LVEDd, LVESd) and fractional shortening (FS) were measured. Haemodynamics was determined at week 9 by LV catheterization and hearts were examined morphologically. Results: Post-infarct mortality was 46% (10/22), of which, 70% died of acute heart failure or LV rupture within the first week. LV dimensions and FS remained stable in SH group (n=10) during the study period. In surviving MI mice (n=12), there was modest LV dilatation and fall in FS at week 1. Compared with week 0 values, there were progressive increase in LVEDd (+50 similar to+66%) and LVESd (+124 similar to+171%), and decline in FS (-53 similar to-73%) during the 2.5 similar to 9 week period. Infarcted mice also had lower LV systolic pressure (LVSP), dP/dt(max) and dP/dt(min) (all P<0.01 vs. SH group). Infarct size, LVSP and dP/dt significantly correlated with FS and LV dimensions (r=0.61 similar to 0.80, all P<0.01). Conclusions: LV remodeling and dysfunction in mice with MI are time-dependent processes and early remodeling seems associated with high risk of rupture and acute pump failure. Our findings provide a baseline description of this murine model and confirm echocardiography as a reliable means to serially assess changes of cardiac structure and function after MI. (C) 2000 Elsevier Science B.V. All rights reserved.

Journal Article Direct aortic distensibility measurements and their reproducibility Get access E. D. LEHMANN, E. D. LEHMANN Guy's and St. Thomas' Hospitals, University of LondonU.K. Search for other works by this author on: Oxford Academic PubMed Google Scholar K. D. HOPKINS, K. D. HOPKINS Guy's and St. Thomas' Hospitals, University of LondonU.K. Search for other works by this author on: Oxford Academic PubMed Google Scholar R. G. GOSLING R. G. GOSLING Guy's and St. Thomas' Hospitals, University of LondonU.K. Search for other works by this author on: Oxford Academic PubMed Google Scholar European Heart Journal, Volume 15, Issue 10, October 1994, Pages 1441–1442, https://doi.org/10.1093/oxfordjournals.eurheartj.a060409 Published: 01 October 1994

Aortic mechanical properties were assessed in a group of elderly subjects with untreated isolated systolic hypertension using two-dimensional echocardiography. Echocardiographic (two-dimensional and Doppler) assessment of left ventricular structure and function was also made. Ten subjects (mean age 71.7 +/- 1.9 years, 20% male, mean clinic blood pressure 163.6/79.2 +/- 1.2/2.0 mmHg) were compared with 16 normotensive subjects of similar age (69.4 +/- 1.6 years, 38% male, mean clinic blood pressure 129.8/78.2 +/- 3.2/2.9 mmHg). Aortic distensibility at the level of the transverse aortic arch was significantly reduced among subjects with isolated systolic hypertension. The thickness of the interventricular septum was approximately 20% greater in the hypertensive subjects (P < 0.01) and the average wall thickness to radius ratio was increased by 30%. Patterns of transmitral diastolic flow were also different in subjects with isolated systolic hypertension. Deceleration time was significantly greater (P < 0.01) and the ratio of early to late transmitral diastolic peak flow velocities was significantly less in the hypertensive (P < 0.05) than in the normotensive group. Left ventricular systolic function was well preserved. These findings are consistent with the suggestion that isolated systolic hypertension represents a state of increased aortic stiffness which may contribute to the development of left ventricular hypertrophy. Whether this increase in aortic stiffness is the cause or effect of the elevated systolic blood pressure remains unresolved.

In previous studies we have shown that administration of 200 mg/day hydrocortisone (cortisol) to normal subjects raises blood pressure and cardiac output, with no change in total peripheral resistance or resting forearm vascular resistance. We have tested the hypothesis that this rise in cardiac output is essential for the rise in blood pressure (BP). Six normal volunteer men, aged 22 to 34 years, took part in two studies of 10 days, in random order, at least 4 weeks apart. Placebo (Study A) or 50 mg atenolol orally, 12 hourly (Study B), was given on days 1 to 10 and 50 mg cortisol orally, 6 hourly, on days 5 to 10. Blood pressure and cardiac output (Fick technique, alternative Doppler) were measured on days 4 and 10. In Study A (placebo and cortisol) systolic BP rose from 116 to 125 mm Hg (standard error of the difference, SED 1.5), P < .01, and in Study B (atenolol and cortisol) from 109 to 120 mm Hg (SED 1.5), P < .01. Cardiac output (indirect Fick) rose from 4.8 +/- 0.01 to 5.9 +/- 0.2 L/min, P < .01, in A, and was unchanged in Study B, 4.4 +/- 0.1 to 4.4 +/- 0.2 L/min. Cardiac output measured by Doppler method was similar in pattern, 5.1 +/- 0.2 to 6.7 +/- 0.2 L/min (P < .01) in A and 5.7 +/- 0.2 to 5.8 +/- 0.2 in B. Calculated peripheral resistance fell in Study A and increased in Study B.(ABSTRACT TRUNCATED AT 250 WORDS)

Non-invasive assessment of mechanical properties of the aorta may prove useful in the early detection of atheroma. We have evaluated several of the available echocardiographic indices using ability to detect age-related changes in putatively disease-free vessels as a measure of sensitivity to changes in aortic mechanical properties. Suprasternal imaging was used in 49 healthy non-smoking volunteers to measure minimum and maximum aortic arch diameters. Maximal flow velocities, with corresponding acceleration times and heart periods, were determined in the descending aorta in 24 of these subjects. Blood pressure was recorded non-invasively immediately after the echocardiographic study. Doppler derived measurements of aortic flow acceleration did not relate to age (P greater than 0.05). Three different 2D echo assessments of aortic distensibility, however, all showed a close relationship to age. Ep elastic modulus and Beta index (derived from different stress-strain mechanical relationships) were significantly related to age with r = 0.69 and 0.65 respectively. There were no significant effects of gender or left ventricular systolic function on these relationships. There was a tendency for the relationship between these distensibility indices and age more closely to fit an exponential than a linear relationship. We conclude that 2D echocardiographic assessment of aortic distensibility is able to detect sensitively changes in aortic mechanical properties. Even in the absence of risk factors for cardiovascular disease there is a marked reduction in aortic distensibility with increasing age.

Reversal of left ventricular hypertrophy (LVH) is an important target of antihypertensive therapy. Nonpharmacological approaches such as weight reduction and exercise training have favorable effects on other risk factors. However, there are few data on their effects on LVH. Athletes have eccentric rather than concentric LVH. A 12-month exercise program in 13 unmedicated hypertensive subjects altered LV geometry, reducing LV wall thickness and increasing LV internal diameters (LVID). LV mass was unchanged, and the thickness/radius fell by 9%. Shorter-term studies have shown that the cardiac structural changes with a moderate exercise program occur rapidly and their onset lags only about 2 weeks behind blood pressure (BP) effects. Assessment of weight loss effects on LVH is complicated by the strong relationship between body weight and ventricular wall thickness. LVID, and LV mass. To some extent, this can be overcome by arbitrarily indexing to body surface area or height. The wall thickness/radius ratio is not related to body size. Weight reduction reduces BP and thickness/radius by 10% in controlled trials. Small studies have also reported reduction in LV mass after sodium restriction in hypertensive subjects. Studies with other nonpharmacological measures could make a substantial contribution to knowledge of their efficacy.

Nebivolol is a β-adrenergic antagonist with novel pharmacodynamic properties. We examined its effects in 8 normal subjects in a randomised double-blind, placebo-controlled crossover study. Nebivolol lowered resting and ambulatory blood pressure (BP). The latter fall averaged 11/10mm Hg after 1 week of therapy (both p < 0.01). The fall in BP was due to a reduction in total peripheral resistance. Stroke volume increased. Nebivolol reduced resting heart rate and heart rate responses to head-up tilting, Valsalva’s manoeuvre and mental challenge. However, BP responses to these stimuli were unaltered. The drug had no effect on plasma noradrenaline (norepinephrine) or on norepinephrine spillover or clearance, either at rest, during mental challenge or tilting. Despite markedly reducing resting heart rate, nebivolol had only a slight effect on left ventricular (LV) dimensions determined echocardiographically. LV systolic function was unchanged but there was evidence of effects on diastolic filling as nebivolol decreased deceleration time (p < 0.003) and pressure half-time.

We examined the prevalence of left ventricular structural and functional abnormalities in previously untreated subjects by performing echocardiography in 89 normal volunteers, 57 patients with established hypertension, and 38 patients with mild or borderline hypertension. We measured left ventricular mass, wall thickness, internal diameter, and wall thickness/radius ratio. Because of intergroup differences in body size, we used covariance analysis to index these variables to a common value of 1.8 m2. No adjustment was needed for the wall thickness/radius ratio. Functional variables determined were fractional shortening and transmitral early/late flow velocity ratio (the latter was standardized by analysis of covariance to age 40 years). The prevalence of left ventricular mass index values more than 2 SD above the mean of the normal group was 30% in the patients with established hypertension and 12-15% in the patients with mild hypertension. Corresponding figures for wall thickness index were 65% and 32% and for the wall thickness/radius ratio 60% and 40%. The prevalence of abnormality in the transmitral flow velocity was 28% in the patients with established hypertension and 12% in the patients with mild hypertension. A multivariate discriminant function that used combined anatomic and functional variables provided the most reliable classification; it was correct in 82% of normal subjects, 65% of patients with established hypertension, and 61% of patients with mild hypertension. The majority of patients with hypertension have cardiac structural or functional abnormalities, or both.

The "chronic" effect of exercise on blood pressure has been controversial and the debate has been confused by a large number of studies with inadequate methodology. Recent consistent findings in epidemiological, experimental and longitudinal intervention studies have suggested that a true antihypertensive effect which is independent of confounding effects of sodium intake, weight, etc. is more likely than not. Unlike some other measures of lowering blood pressure such as sodium restriction, alcohol moderation and some drugs, regular exercise is associated with beneficial effects on several risk factors and probably has an independent effect on cardiovascular mortality. The magnitude of the effect in previously sedentary subjects is greater than that of dietary measures which lower blood pressure except for weight reduction in the obese. Long-term effects on blood pressure are supported by evidence of a favourable influence on left ventricular hypertrophy. The mechanisms involved in the antihypertensive effect of exercise are unclear, but sympathetic withdrawal is one factor involved. Present evidence appears sufficient to include regular exercise amongst the useful therapies for hypertension.

This study was performed to determine the relative contributions of plasma norepinephrine clearance and norepinephrine release to the increase in plasma norepinephrine concentration that occurs during exercise and to determine whether the high rates of cardiac norepinephrine release from the heart and kidney in patients with heart failure are associated with diminished reserve for regional sympathetic nervous stimulation. During supine steady-state bicycle exercise at 50% of maximum voluntary exercise capacity, the plasma norepinephrine concentration of six patients with congestive heart failure rose from 385 +/- 88 to 2,200 +/- 497 pg/ml, whereas that of nine normal subjects rose from 208 +/- 21 to 882 +/- 257 pg/ml. The change in plasma concentration in both groups was due to an increase in norepinephrine spillover to plasma without a change in plasma norepinephrine clearance. In patients with heart failure, cardiac spillover increased from 80 +/- 26 to 528 +/- 265 ng/min during exercise, and renal spillover rose from 146 +/- 71 to 418 +/- 69 ng/min. In the normal subjects, cardiac spillover rose from 5 +/- 2 to 73 +/- 23 ng/min, and renal spillover increased from 76 +/- 27 to 275 +/- 106 ng/min. There is no evidence of a reduced reserve for overall or regional sympathetic stimulation in patients with heart failure. Reduced reflex responses in these patients are more likely due to end-organ refractoriness than to inadequate stimulation.

We studied the hemodynamic effects of four doses of milrinone, administered by intravenous (i.v.) infusion alone and after autonomic blockade with prazosin, propranolol, atropine, and clonidine. Plasma concentrations of milrinone (50-600 ng/ml) were similar to those used for the treatment of cardiac failure and were unaltered by autonomic blockade. When given alone, milrinone induced dose-dependent increases in heart rate (maximum increase 21 +/- 4, SEM, beats/min) and cardiac output (CO) (maximum 44 +/- 9%) and reduced systemic vascular resistance (SVR) by a maximum of 32 +/- 5%. After autonomic blockade, milrinone caused a similar fall in SVR and a smaller but significant (7 +/- 2 beats/min) rise in heart rate, but no change in CO. The increase in CO produced in normal humans by acute i.v. infusions of milrinone depends on intact cardiovascular reflexes.