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Background: Renal denervation (RDN) may lower blood pressure (BP); however, it is unclear whether medication changes may be confounding results. Furthermore, limited data exist on pattern of ambulatory blood pressure (ABP) response-particularly in those prescribed aldosterone antagonists at the time of RDN., Methods: We examined all patients treated with RDN for treatment-resistant hypertension in 18 UK centres., Results: Results from 253 patients treated with five technologies are shown. Pre-procedural mean office BP (OBP) was 185/102 mmHg (SD 26/19; n = 253) and mean daytime ABP was 170/98 mmHg (SD 22/16; n = 186). Median number of antihypertensive drugs was 5.0: 96 % ACEi/ARB; 86 % thiazide/loop diuretic and 55 % aldosterone antagonist. OBP, available in 90 % at 11 months follow-up, was 163/93 mmHg (reduction of 22/9 mmHg). ABP, available in 70 % at 8.5 months follow-up, was 158/91 mmHg (fall of 12/7 mmHg). Mean drug changes post RDN were: 0.36 drugs added, 0.91 withdrawn. Dose changes appeared neutral. Quartile analysis by starting ABP showed mean reductions in systolic ABP after RDN of: 0.4; 6.5; 14.5 and 22.1 mmHg, respectively (p < 0.001 for trend). Use of aldosterone antagonist did not predict response (p > 0.2)., Conclusion: In 253 patients treated with RDN, office BP fell by 22/9 mmHg. Ambulatory BP fell by 12/7 mmHg, though little response was seen in the lowermost quartile of starting blood pressure. Fall in BP was not explained by medication changes and aldosterone antagonist use did not affect response.

Aortic atherosclerosis reduces compliance in the systemic circulation and increases peripheral resistance, afterload and left ventricular wall stress. In patients with heart failure, these changes can impair left ventricular systolic function and energy efficiency, which could reduce exercise capacity. Though the interaction and the impact of aortic atherosclerosis on left ventricular function have been investigated, its prognostic implications in patients with heart failure are unclear. We used cardiac magnetic resonance imaging and gadolinium-enhanced abdominal aortography to investigate the prevalence and prognostic impact of atherosclerotic disease of the abdominal aorta and its side branches in 355 patients with heart failure. Sclerotic abdominal aortic disease was defined as a luminal narrowing >50% of the aorta and its side branches or the presence of abdominal aortic aneurysm. Patients with disease of the aorta and its branches were older (P < 0.0001), had overall longer stay in hospital (P = 0.006) and had more admissions (P = 0.001) and worse prognosis (hazard ratio: 1.97, 95% confidence interval: 1.29-3.00, P = 0.002) than those without. In a multivariable model, increasing age and pulse pressure, diabetes mellitus and increasing left ventricular end-diastolic volume were associated with a worse prognosis, but sclerotic abdominal aortic disease was not independently related to outcome (hazard ratio: 1.06; 95% confidence interval: 0.64-1.74; P = 0.823). These data demonstrate that atherosclerosis of the abdominal aorta and its side branches is common and associated with increased morbidity in patients with chronic heart failure. How such disease should be managed remains uncertain, but its recognition and characterisation are the first steps in finding out.

Background: Beta-blockers are effective for the treatment of heart failure, but their mechanism of action is unresolved. Heart rate reduction may be a central mechanism or a troublesome side effect., Methods: A randomized, double-blind, parallel group study comparing chronic higher-rate (80 pulses per minute) with lower-rate (60 pulses per minute) pacing in pacemaker-dependent patients with symptomatic left ventricular (LV) systolic dysfunction, receiving beta-blockers. Gated radionuclide ventriculography (RNVG) was performed at baseline and after at least 9 months. The primary outcome was change in LV volumes, as a marker of beneficial reverse remodeling, from baseline to follow-up., Results: Forty-nine patients were randomized. Mean age was 74 +/- 6 years and with LV ejection fraction of 26% +/- 9% at baseline. During 14 +/- 13 months of follow-up, 21 patients (43%) died and 25 (51%) completed the study protocol: 12 in the higher-rate and 13 in the lower-rate group. Mean LV end-diastolic (higher rate +20 +/- 104 mL vs lower rate -65 +/- 92 mL, P = .03) and systolic (higher rate +29 +/- 83 mL vs lower rate -60 +/- 74 mL, P = .006) volumes increased with higher-rate versus lower-rate pacing, whereas LV ejection fraction declined (higher rate -4.2% +/- 4.4% vs lower rate +2.2% +/- 5.4%, P = .002)., Conclusion: Reversal of beta-blocker-induced bradycardia has deleterious effects on ventricular function, suggesting heart rate reduction is an important mediator of their effects. The prognosis of patients with pacemakers and heart failure is poor.

Aims: Different methods exist for measuring left ventricular function echocardiographically; each may be error prone due to the abnormal pattern of ventricular activation during pacing., Methods and Results: Echocardiography was undertaken on 307 patients with permanent pacemakers; a subset of 57 underwent radionuclide ventriculography. Intrinsic and paced beats were analysed for left ventricular function by: Simpson's bi-plane, Teicholz M-mode, wall-motion scoring and 'eyeball' assessment. Agreement between techniques and with radionuclide ventriculography were compared according to intrinsic or paced beats. Echocardiographic measures of ejection fraction give mean values 5% higher than radionuclide ventriculography (Simpson's 30+/-9%, vs. Teicholz 30+/-13% vs. radionuclide ventriculography 25+/-9%, p=0.03). Agreement between Simpson's, Teicholz and radionuclide ventriculography by Bland-Altman analysis showed poor agreement (Simpson's vs. Teicholz range (4xSD)=57%, Simpson's vs. radionuclide ventriculography=36%, Teicholz vs. radionuclide ventriculography=46%, p=0.02), the level of agreement deteriorates with ventricular pacing (Simpson's vs. Teicholz range=61%, Simpson's vs. radionuclide ventriculography=34%, Teicholz vs. radionuclide ventriculography=47%, p=0.02). The correlation between wall motion analysis and radionuclide ventriculography is moderately poor (all subjects r=0.58, ventricular pacing r=0.52, not pacing r=0.66)., Conclusion: Echocardiography and radionuclide ventriculography are the only non-invasive techniques to assess left ventricular function in the paced population. Results are poorly interchangeable and the accuracy of any comparison dependent on the underlying rhythm.

Aims: Assessment of N-terminal brain natriuretic peptide (NT-BNP) as a screening tool for heart failure in patients with a permanent pacemaker., Methods and Results: Consecutive patients undergoing a routine permanent pacemaker assessment were enrolled. Patients underwent medical history and examination, echocardiography and blood sampling for NT-BNP. Analysis was performed on 261 patients (132 DDD, 121 VVI, eight others), mean age 73+/-12 years, range 34-99 years. Seventy two subjects (27%) had heart failure as defined by left ventricular ejection fraction (LVEF)

Background: The kinetics of oxygen and carbon dioxide at the onset of and recovery from exercise are slowed in patients with chronic heart failure (CHF). The aim of the present study was to establish whether the kinetics of O2 are influenced by the work rate., Methods: Thirteen CHF patients and 12 control subjects underwent bicycle-based peak exercise testing with metabolic gas exchange analysis. Each subject then exercised at 15%, 25% and 50% of the maximal workload achieved until reaching steady state. Time constants for onset (T(onset)) and offset (T(offset)) for O2 uptake and CO2 output were correlated to the workload and the percentage of peak V(O2) performed during the steady state tests., Results: Patients had lower peak oxygen uptake (pV(O2)) and the relation between ventilation and carbon dioxide output was steeper in patients than controls. T(offset) for both oxygen (O2) and carbon dioxide (CO(2)) from peak exercise was significantly greater in the patients than the controls and correlated with peak V(O2) (r=0.56, p<0.005 and r=0.58, p<0.005). T(onset) and T(offset) for O2 were increased in patients for each of the steady state tests and peak V(O2) correlated with T for recovery of O2 (r=0.44; p<0.05 from 15%, r=0.35; p= or <0.05 from 25%, and r=0.54; p<0.01 from 50%). There was a correlation between the T(onset) (r=0.42; p<0.0005 for O2 and r=0.23; p<0.05 for CO2) and T(offset) (r=0.49; p<0.0001 for O2 and r=0.42; p<0.0005 for CO2) and oxygen uptake as a percentage of peak exercise., Conclusions: This study demonstrates that the time constants of onset and offset for oxygen are dependent upon the degree of exertion performed relative to the individual's peak capacity.

Objective: To assess the influence of acute alpha and beta blockade on ventilation and symptoms of breathlessness during exercise in patients with chronic heart failure and in controls., Methods: 11 patients with chronic heart failure and 11 control subjects underwent repeated exercise testing with metabolic gas exchange after random, double blind administration of either an alpha blocker and placebo, a beta blocker and a placebo, both an alpha blocker and a beta blocker, or double placebo., Results: Patients had a lower peak oxygen consumption (mean (SD) 20.7 (4.9) v 37.6 (9.6) ml/kg/min, p < 0.0001) and a steeper slope relating ventilation to carbon dioxide production (VE/CO2 slope) (26.5 (4.1) v 37.1 (8.2), p = 0.0011), than controls. Blood pressure was lower following alpha and beta blockade (p < 0.05) and the gradients of the slopes relating heart rate to oxygen consumption following the beta blocker were reduced (p < 0.05). Exercise time and peak ventilatory variables following beta or alpha blockers were unchanged. Ventilation was reduced during submaximal exercise following the active medications. Combined alpha and beta blockade produced the greatest difference (p < 0.005), but the alpha and beta blockers alone also reduced ventilation (p < 0.05). There was no difference in perceived exertion during exercise with any of the treatments., Conclusion: Acute sympathetic inhibition can reduce submaximal ventilation during exercise in patients with heart failure and control subjects, suggesting that autonomic nervous system activation has an important role in the abnormal ventilatory response to exercise in chronic heart failure.

Objective: Quantitative 2-dimensional color Doppler tissue imaging is a new method to reveal impairment of left ventricular (LV) and right ventricular (RV) longitudinal function, which is a potential marker of early myocardial disease. The aim of this study was to obtain normal values for atrioventricular annular and regional myocardial velocities using this method., Methods: A total of 123 healthy patients (age range: 22 to 89 years) underwent echocardiography including color Doppler tissue imaging using a scanner (Vivid 5, GE Vingmed, Horten, Norway) with postprocessing analysis (Echopac 6.3, GE Vingmed). Regional myocardial velocities were measured at 12 LV segments in 3 apical views and 2 segments of the free RV wall. Mitral annular velocities from 6 sites, and tricuspid annular velocities at its lateral site, were also assessed. At each site, systolic (S(m)), early diastolic (E(m)), and late diastolic (A(m)) velocities were measured, and the E(m)/A(m) ratio was calculated., Results: Patients were classified into 4 groups aged 20 to 39, 40 to 59, 60 to 79, and >/=80 years. Mitral annular velocity and regional LV myocardial S(m) and E(m) progressively decreased with age. A(m), whereas low in the youngest age group, increased significantly in patients more than 40 years of age. The E(m)/A(m) ratio gradually declined with aging. There were no differences between age groups in S(m) measured at the tricuspid annulus and free RV wall, but the pattern of age-related changes of diastolic velocities and E(m)/A(m) ratio was the same as in the LV. Slight but significant sex-related differences were observed in middle-aged groups. The intraobserver and interobserver reproducibility was highest for atrioventricular annular velocities., Conclusions: A progressive decrease in S(m) reveals a decline in longitudinal systolic LV function with age, whereas systolic RV function remains unaffected. Atrioventricular annular velocity and regional E(m) decrease with aging in both ventricles, suggesting a deterioration in the diastolic properties of the myocardium, whereas A(m) increases from middle age implying a compensatory augmentation of atrial function. The study results can be used as reference data for the quantitative assessment of longitudinal LV and RV function in patients with cardiac disease.

Aims: To assess the prevalence of heart failure and asymptomatic left ventricular systolic dysfunction in the chronically paced population., Methods and Results: Three hundred and seven patients were identified from attendance at routine pacemaker follow-up clinic. Subjects underwent a medical history and examination, 6-minute walk test and echocardiography. 94 (31%) had a left ventricular ejection fraction (LVEF) <40%, of whom 83 had symptoms of heart failure (70% NYHA II, 26% NYHA III and 4% NYHA IV). Heart failure was more prevalent in patients with single chamber compared to dual chamber pacemakers, (DDD(R) 18% vs 35% VVI(R), p<0.008), and those with chronic atrial fibrillation (AF) compared to those with sinus rhythm (42% vs 21%, p=0.003). Decreasing 6-minute walk distance, history of ischaemic heart disease and years of pacing were independently associated with the presence of heart failure (combined R=0.572, p<0.001)., Conclusions: Heart failure due to left ventricular systolic dysfunction is common in the paced population. Only a minority of these had a pre-existing diagnosis and a smaller proportion were on 'optimal' therapy. Echocardiographic screening of this high-risk population is justified to improve rates of diagnosis and treatment of heart failure.

Objective: To determine the pattern of the abnormal ventilatory response in heart failure and how it relates to symptoms by looking at tidal volume (VT) and frequency (f) during exercise., Methods: 45 patients with heart failure and 21 controls underwent maximal treadmill based exercise testing with metabolic gas exchange analysis. The relation of ventilation (VE) to VT was plotted to look for an inflection point where VT failed to increase further. The slope of the relation before this inflection point was documented. Time to the inflection point, VT, and f at the inflection point were recorded. The relation of symptom scores to f and E was also examined., Results: Peak oxygen consumption (PVO2) (mean (SD)) was lower (19.7 (4.5) v 37.9 (8.6) ml/kg/min; p < 0001) and the ventilation to carbon dioxide production (VE/VCO2) slope was steeper (40.0 (6.5) v 26.0 (1.6); p < 0.0001) in patients with heart failure than in the control group. The patients reached the inflection point of the VE/VT slope sooner during exercise than the controls (271 (110) v 502 (196) seconds; p < 0.0001). Patients had a higher f and a smaller VT at that point and throughout exercise until the peak where f was the same for patients and controls. VT at the inflection point correlated with PVO2 (r = 0.67; p < 0.0001). Despite having an increased sensation of breathlessness for a given E, patients were less symptomatic of f than controls., Conclusions: Patients with heart failure breathe at a higher f throughout exercise, reaching an apparent maximal VT earlier. The VT at an inflection point on the VE/VT slope predicts PVO2.

Aims: Left atrial function is abnormal in a wide range of cardiac diseases. This study was designed to assess the effects of normal ageing and sex on left atrial morphology and function., Methods and Results: Echocardiography was performed in 123 subjects (age 57 +/- 19 years, range 22 to 89 years, 59 women) with no evidence of cardiovascular disease. M-mode derived left atrial size, B-mode derived left atrial maximal and minimal volumes, and the volume at onset of atrial systole (P-volume) were measured. Left atrial filling, active and passive emptying volumes and ejections fractions, and expansion index were calculated. Subjects were divided into four groups according to age. Left atrial diameter increased with age, with significantly smaller left atrial size in younger subjects. The oldest subjects had significantly higher (P<0.05) left atrial minimal, maximal and P-volume indices. Filling volume index was highest in the oldest subjects (21.9 +/- 5.6 ml/m(2)). Passive emptying volume index was the lowest in those of middle age (10.5 +/- 2.8 ml/m(2)). Active emptying volume index progressively increased with age (P<0.001). Left atrial expansion index and active emptying fraction were not different between the age groups. There was significant difference in passive emptying fraction (P<0.001) with highest values in the youngest (44.7 +/- 7.3%) and lowest values in the oldest subjects (33.6+/-5.4%)., Conclusions: Age- and sex-related reference values of echocardiographic indices of left atrial morphology and function are reported. Ageing is associated with left atrial dilatation. Left atrial conduit function deteriorates with age while reservoir and pump function are maintained. Left atrial anteroposterior diameter is smaller in women than in men, but overall left atrial function is not influenced by sex., (Copyright 2002 The European Society of Cardiology. Published by Elsevier Science Ltd. All rights reserved.)