Gender differences in variables related to B-natriuretic peptide, left ventricular ejection fraction and mass, and peak oxygen consumption, in patients with heart failure.

AIM AND METHODS: We assessed gender differences in variables related to B-natriuretic peptide (BNP), left ventricular ejection fraction (LVEF), peak oxygen consumption (peak-VO2), and LV mass (LVM), among patients recently hospitalized for suspected heart failure (HF). RESULTS: Of 930 consecutive patients, 409 accepted follow-up after discharge, 221 of these had definite HF (90 women, mean age 74.5 [9.8]years). In 141 HF patients (61 women) with BNP data, women had lower BNP than men (43.9 [38.1] versus 76.3 [88.9]pmol/L, P=0.0193). LVEF (all HF patients) was higher in women (49.8 [13.4] versus 42.4 [13.9]%, P=0.0004). Peak-VO2 (147 HF patients, 48 women) was lower in women (13.9 [4.3] versus 16.3 [4.2]mL/kg/min, P=0.0093). LVM index (200 HF patients, 78 women) was lower in women (130.4 [46.5] versus 171.7 [57.6]g/m(2), P<0.0001). Among HF patients, variables independently related to BNP were body mass index (BMI) and peak-VO2 exclusively among men, mitral regurgitation, respiratory disease and angiotensin receptor blocker treatment only among women. Variables independently related to LVEF were resting heart rate, acetylic salicylic acid use and BNP exclusively among men. No variable was exclusive for women. Variables independently related to peak-VO2 were right ventricular size, BNP, resting and peak heart rate solely among men, BMI and stable angina pectoris exclusively among women. Variables independently related to LVM were left atrial diameter only among men, BMI exclusively among women. CONCLUSION: Among elderly HF patients, there were some important gender differences in BNP, LVEF, peak-VO2 and LVM, and in variables independently related to these factors.

Parametric quantification of myocardial ischaemia using real-time perfusion adenosine stress echocardiography images, with SPECT as reference method.

SUMMARY BACKGROUND: Real-time perfusion (RTP) adenosine stress echocardiography (ASE) can be used to visually evaluate myocardial ischaemia. The RTP power modulation technique, provides images for off-line parametric perfusion quantification using Qontrast software. From replenishment curves, this generates parametric images of peak signal intensity (A), myocardial blood flow velocity (beta) and myocardial blood flow (Axbeta) at rest and stress. This may be a tool for objective myocardial ischaemia evaluation. We assessed myocardial ischaemia by RTP-ASE Qontrast((R))-generated images, using 99mTc-tetrofosmin single-photon emission computed tomography (SPECT) as reference. METHODS: Sixty-seven patients admitted to SPECT underwent RTP-ASE (SONOS 5500) during Sonovue infusion, before and throughout adenosine stress, also used for SPECT. Quantitative off-line analyses of myocardial perfusion by RTP-ASE Qontrast-generated A, beta and Axbeta images, at different time points during rest and stress, were blindly compared to SPECT. RESULTS: We analysed 201 coronary territories [corresponding to the left anterior descendent (LAD), left circumflex (LCx) and right coronary (RCA) arteries] from 67 patients. SPECT showed ischaemia in 18 patients. Receiver operator characteristics and kappa values showed that A, beta and Axbeta image interpretation significantly identified ischaemia in all territories (area under the curve 0.66-0.80, P = 0.001-0.05). Combined A, beta and Axbeta image interpretation gave the best results and the closest agreement was seen in the LAD territory: 89% accuracy; kappa 0.63; P<0.001. CONCLUSION: Myocardial isachemia can be evaluated in the LAD territory using RTP-ASE Qontrast-generated images, especially by combined A, beta and Axbeta image interpretation. However, the technique needs improvements regarding the LCx and RCA territories.

Gender aspects on heart failure incidence and mortality in a middle-aged, urban, community-based population sample: the Malmö preventive project.

UNLABELLED: There is little epidemiological data on heart failure (HF) in the younger age groups dominating clinical HF trials. We assessed gender-specific long-term HF incidence and mortality in an urban community-based sample of middle-aged subjects. Between 1974 and 1992, 33,342 HF-free subjects (10,900 [32.7%] women, mean age 45.7 +/- 7.4 years) were included in the Malmö Preventive Project, on average 21.7 +/- 4.3 years before study end. Patients hospitalised for or dying of HF were categorised as HF patients, and 120 (1.1%) women versus 644 (2.9%) men experienced HF: 6.0 vs. 12.3 cases per 10,000 person years; hazard ratio [HR] 0.61, 95% confidence interval [CI] 0.50-0.74, P < 0.0001. Among all subjects, women compared with men had lower all-cause (49.3 vs. 84.0 cases per 10,000 person years; HR 0.68, 95% CI 0.64-0.73, P < 0.0001) and HF-related (2.6 vs. 7.4 cases per 10,000 person years; HR 0.50, 95% CI 0.37-0.67, P < 0.0001) mortality risk. Female and male HF patients had similar age-adjusted mortality risk: 1,314 vs. 1,602 cases per 10,000 patient years; HR 0.78, 95% CI 0.58-1.07, P = 0.12. Among HF patients, 55.3% of deaths in women and 40.6% in men were non-cardiovascular, and only 7.9% deaths were due to HF. IN CONCLUSION: In a middle-aged, urban, community-based sample, women had lower risk of HF, all-cause death and HF-related death over two decades of follow-up. Female and male HF patients had similar mortality risk after the diagnosis of HF. In these comparatively young HF patients, few deaths were due to HF and more than 4 out of 10 deaths were non-cardiovascular.

Gender aspects on survival among patients admitted to hospital with suspected or diagnosed heart failure.

OBJECTIVES AND DESIGN: There are conflicting data on gender differences in survival among heart failure (HF) patients. We prospectively assessed gender differences in survival among 930 consecutive patients (464 [49.9%] women, mean age 76.1+/-10.1 years), admitted to hospital with suspected or diagnosed HF. RESULTS: Overall, women had lower unadjusted mortality hazard ratio (HR) than men: HR 0.827; 95% confidence interval (CI) 0.690-0.992; p=0.040. Adjusted HR was 0.786; 95% CI 0.601-1.028; p=0.079. Unadjusted mortality was significantly higher among patients with a discharge HF diagnosis, compared to those without: HR 1.330; 95% CI 1.107-1.597; p=0.002; adjusted p=0.289. Women and men with a discharge HF diagnosis had similar survival: unadjusted HR 1.052; 95% CI 0.829-1.336; p=0.674; adjusted HR 0.875; 95% CI 0.625-1.225; p=0.437. Women had lower mortality risk among patients without a discharge HF diagnosis: HR 0.630, 95% CI 0.476-0.833, p=0.001; adjusted HR 0.611, p=0.036. CONCLUSION: Prognosis was poor among patients hospitalised with suspected or diagnosed HF. Among all patients, women had better survival, whereas both sexes had similar survival when the HF diagnosis was certified.

Self-rated health and classical risk factors for coronary heart disease predict development of erectile dysfunction 25 years later.

AIM: To investigate the impact of classical coronary heart disease (CHD) risk factors on the development of future erectile dysfunction (ED). METHODS AND RESULTS: A total of 830 randomly selected subjects were included. Baseline CHD risk factors were evaluated in relation to ED (evaluated by the International Index of Erectile Function-5 questionnaire) 25 years later. At follow-up, 499 men (60%) had some degree of ED. In age-adjusted logistic regression analysis, self-rated health [odds ratio (OR) 1.59, 95% confidence interval (CI): 1.09-2.31], family history of CHD (OR 1.75, CI: 1.17-2.61), fasting blood glucose (OR 1.52, CI: 1.14-2.02), triglycerides (OR 1.25, CI: 1.01-1.54), systolic blood pressure (SBP) (OR 1.19, CI: 1.04-1.35), body mass index (OR 1.08, CI: 1.03-1.13) and serum glutamyl transferase (GT) (OR 1.81, CI: 1.23-2.68), predicted ED. Independent predictors were higher age, low self-rated health, higher blood glucose, higher GT and a family history of CHD. Higher SBP was borderline significantly independent (p=0.05). Furthermore, baseline age-adjusted Framingham risk score for CHD, also predicted future ED (OR 1.20, CI: 1.03-1.38). CONCLUSIONS: Our study supports and expands previous findings that ED and CHD share many risk factors, further underscoring the close link between ED and CHD. Men presenting with ED should be evaluated for the presence of other CHD risk factors.

Real-time perfusion adenosine stress echocardiography versus myocardial perfusion adenosine scintigraphy for the detection of myocardial ischaemia in patients with stable coronary artery disease.

BACKGROUND: Real-time perfusion (RTP) contrast echocardiography using low mechanical index power modulation technique allows for simultaneous myocardial perfusion and wall motion analysis. RTP-adenosine stress echocardiography (ASE) could be an alternative to dobutamine-atropine stress echocardiography; more tolerable for the patients and possibly similarly accurate. We aimed to evaluate RTP-ASE for the detection of myocardial ischaemia, compared to 99mTc-sestamibi single-photon emission computed tomography (SPECT). METHODS: Patients with suspected coronary artery disease, admitted to SPECT evaluation, were prospectively invited to participate. Patients underwent RTP imaging (SONOS 5500) using infusion of Sonovue (Bracco, Milano, Italy) before and during ASE. Two separate readers performed off-line analysis of myocardial perfusion and wall motion by RTP-ASE. A perfusion defect was the principal marker of ischaemia. Wall motion assessment was used to evaluate ischaemia in segments with perfusion artefacts. Each segment was attributed to one of the three main coronary vessel areas of interest: the left anterior descending (LAD); the left circumflex (LCx) and the right posterior descending (RPD). Normal SPECT at stress was judged normal at rest. RESULTS: In 33 patients, 99 coronary territories were analysed by SPECT and RTP-ASE. SPECT showed evidence of ischaemia in 9 of 33 patients. For the detection of ischaemia, the overall level of agreement between RTP-ASE and SPECT was 92% in all segments. The level of agreement was 88% in LAD, 97% in LCx and 91% in RPD segments. CONCLUSION: Real-time perfusion-adenosine stress echocardiography using power modulation could be an accurate and feasible tool for evaluation of ischaemia in patients with suspected coronary artery disease. The results from this study need confirmation by a study of a larger patient sample.

Left atrioventricular plane displacement but not left ventricular ejection fraction is influenced by the degree of aortic stenosis.

AIMS: To examine how left atrioventricular plane displacement (AVPD), a widely used measure of left ventricular (LV) function, is related to presence and degree of aortic stenosis. METHODS AND RESULTS: Cardiac dimensions, LV filling, left AVPD, LV ejection fraction (LVEF), and valve function were assessed by echocardiography/Doppler in 182 patients with various cardiac diseases (mean (SD) age 69 (12) years, 36% women), 49 consecutive with and 133 consecutive without aortic stenosis. In an analysis of covariance, neither left AVPD nor LVEF was independently correlated with the presence of aortic stenosis. However, looking separately at patients with aortic stenosis, left AVPD (p = 0.03) but not LVEF correlated independently with degree of aortic stenosis in multiple linear regression analysis. In patients with aortic stenosis, an abnormal left AVPD had 94% sensitivity and 90% negative predictive value with regard to severe aortic stenosis, compared with 56% and 62%, respectively, for LVEF. CONCLUSION: In patients with cardiac disease, neither left AVPD nor LVEF correlated independently with presence of aortic stenosis. However, in patients with aortic stenosis, left AVPD but not LVEF correlated with the degree of aortic valve obstruction and left AVPD but not LVEF had high sensitivity and negative predictive value with regard to severe aortic stenosis. Compared with LVEF, left AVPD is an earlier and more sensitive marker of LV haemodynamic load in patients with aortic stenosis.

Left atrioventricular plane displacement determined by echocardiography: a clinically useful, independent predictor of mortality in patients with stable coronary artery disease.

BACKGROUND: Echocardiographically determined left atrioventricular plane displacement (AVPD) is strongly related to prognosis in patients with chronic heart failure and in postmyocardial infarction patients. We aimed at exploring whether AVPD, unlike ejection fraction, is related to mortality in patients with stable coronary artery disease (CAD). METHODS AND RESULTS: Atrioventricular plane displacement was assessed by two dimensionally guided M-mode echocardiography in the four and two chamber views, in 333 consecutive patients with stable CAD and an abnormal coronary angiogram. Patients were followed up for an average of 41 months. AVPD was lower in patients who died (n= 30, 9.0 %) compared with survivors (9.0 +/- 2.2 vs. 11.5 +/- 2.1 mm, P<0.0001). Amongst patients with prior myocardial infarction (n=184) AVPD was 8.7 +/- 2.3 mm in those who died (n=17) and 11.2 +/- 2.3 mm in the survivors (P<0.0001). In patients without prior myocardial infarction (n=149), AVPD was 9.4 +/- 2.1 (n=13) and 11.8 +/- 1.8 mm, respectively (P<0.0001). Age, AVPD and four other echocardiographical variables correlated significantly with prognosis in univariate logistic regression analysis. In multiple logistic regression analysis only AVPD (P<0.0001) correlated independently with mortality. CONCLUSION: Echocardiographically determined AVPDis a clinically useful, independent prognostic tool in patients with stable CAD. The presence of a documented previous myocardial infarction does not influence this observation.

Improved cardiac function and quality of life following upgrade to dual chamber pacing after long-term ventricular stimulation.

AIMS: Many patients with sinus node disease or atrioventricular block have previously received pacemakers with only ventricular stimulation (VVI or VVIR). This study aimed to investigate whether quality of life and cardiac function were affected by an upgrade to dual chamber pacing (DDDR or DDIR) following long-term ventricular stimulation. METHODS: After implantation of an atrial lead and a DDDR pulse generator, a randomized, double-blind crossover study was performed in 19 patients, previously treated with ventricular pacing for a median time of 6 X 8 years. Patients were randomized to 8 weeks with either VVIR or DDDR/DDIR pacing; after this time, the other mode was programmed for 8 weeks. At the end of each period, the patients' quality of life was evaluated and echocardiography was performed together with Holter monitoring and blood samples for brain natriuretic peptide. RESULTS: Sixteen of the patients preferred DDDR and two VVIR pacing (P=0 X 001); one was undecided. Seven patients demanded an early crossover while paced in the VVIR mode, vs none in the DDDR mode (P=0 X 008). Quality of life was higher in the DDDR mode in 11 of 17 modalities, reaching statistical significance for dyspnoea (P<0 X 05) and general activity (P<0 X 05). Echocardiography showed significantly larger left ventricular end-diastolic dimensions in the DDDR mode (P=0 X 01), whereas end-systolic dimensions did not differ. Left ventricular systolic function was significantly superior in the DDDR mode (mean aortic velocity-time integral: P<0 X 001) and left atrial diameter was significantly smaller in the DDDR mode (P=0 X 01). The plasma level of brain natriuretic peptide was significantly lower in DDDR mode (P=0 X 002). CONCLUSION: An upgrade to dual chamber rate adaptive pacing results in significantly improved quality of life and cardiac function as compared to continued VVIR stimulation and should thus be considered in patients with ventricular pacemakers who have not developed permanent atrial fibrillation or flutter.

Statistical significance versus clinical relevance in cardiovascular medicine.

Evidence-based medicine is the foundation of everyday clinical practices and large clinical trials investigating the effects of various interventions on morbidity and survival and generally provide the most robust evidence. Cardiovascular medicine is considered one of the most evidence-based disciplines of medicine. However, there are a number of limitations to the general applicability of clinical trial results in cardiovascular medicine. Although generally useful to the clinician, clinical trials have often been suboptimally designed from 1 or several points of view. As a consequence of flaws in the design and the execution of the trials, statistical significance is quite often not equal to clinical relevance. This article outlines some of the shortcomings of designing and carrying out clinical trials, as well as inadequacies concerning the publication, interpretation, and implementation of the trial results. Evidence-based medicine is obviously not always as solid as one might think.

Left ventricular diastolic filling is related to the atrioventricular plane displacement in patients with coronary artery disease.

OBJECTIVE: Left atrioventricular plane displacement (AVPD) is often decreased and abnormalities in left ventricular diastolic filling are common in patients with coronary artery disease (CAD). This study was designed to assess the relationship between AVPD and diastolic filling in patients with CAD. DESIGN: AVPD was assessed by echocardiography and diastolic filling by transmitral and pulmonary venous pulsed Doppler in 170 consecutive patients (66 +/- 11 years) with proven CAD at coronary angiography. Diastolic filling was grouped as normal, mildly impaired and moderately to severely impaired. RESULTS: A simple linear regression analysis showed that AVPD decreased in relation to increased severity of diastolic filling impairment (r = -0.36, p < 0.0001). In a multiple regression analysis, ejection fraction, diastolic filling, age and body surface were independently correlated with AVPD. Each millimetre of decrease in AVPD increased the probability of impaired diastolic filling by 28%. CONCLUSION: AVPD was independently correlated with both left ventricular systolic function and diastolic filling in patients with CAD. Thus, given the same degree of ejection fraction, it was found that the greater the impairment in diastolic filling, the lower the AVPD.

Effects on quality of life, symptoms and daily activity 6 months after termination of an exercise training programme in heart failure patients.

BACKGROUND: Exercise training in heart failure patients improves exercise capacity, physical function, and quality-of-life. Prior studies indicate a rapid loss of these effects following termination of the training. We wanted to assess any sustained post-training effects on patients global assessment of change in quality-of-life (PGACQoL) and physical function. METHODS: Fifty-four stable heart failure patients were randomised to exercise or control. The 4-month exercise programme consisted of bicycle training at 80% of maximal intensity three times/week, and 49 patients completed the active study period. At 10 months (6 months post training) 37 patients were assessed regarding PGACQoL, habitual physical activity, and dyspnea-fatigue-index. RESULTS: Both post-training patients (n=17) and controls (n=20) deteriorated PGACQoL during the 6-month extended follow-up, although insignificantly. However, post-training patients improved PGACQoL slightly but significantly from baseline to 10 months (P=0.006), differing significantly (P=0.023) from controls who were unchanged. Regarding dyspnea-fatigue-index, post-training patients were largely unchanged and controls deteriorated insignificantly, during the extended follow-up as well as from baseline to 10 months. Both groups decreased physical activity insignificantly during the extended follow-up, and from baseline to 10 months post-training patients tended to decrease whereas controls significantly (P=0.007) decreased physical activity. CONCLUSION: There was no important sustained benefit 6 months after termination of an exercise training programme in heart failure patients. A small, probably clinically insignificant sustained improvement in PGACQoL was seen in post-training patients. Controls significantly decreased the habitual physical activity over 10 months and post-training patients showed a similar trend. Exercise training obviously has to be continuing to result in sustained benefit.

Left ventricular early diastolic inflow velocity and atrial ventricular plane downward velocity: useful parameters to test diastolic function in clinical practice? Diastolic parameters tested in a clinical setting.

AIMS: To study the clinical value of the colour-M-mode slope of the early diastolic left ventricular filling phase (Vp) and the early diastolic downward M-mode slope of the left atrioventricular plane displacement (EDS), compared with diastolic function assessed by traditional Doppler evaluation. METHODS AND RESULTS: In 65 consecutive patients EDS and Vp were compared with a four-degree traditional diastolic function classification, based on pulsed Doppler assessment of the early to atrial transmitral flow ratio (E/A), the E-wave deceleration time (Edt), and the systolic to diastolic (S/D) pulmonary venous inflow ratio. Vp (P=0.006) and EDS (P=0.045) were related to traditional diastolic function (Kruskal--Wallis analysis). EDS showed a trend brake between the moderate and severe diastolic dysfunction groups by traditional Doppler evaluation. Vp and EDS correlated weakly in simple linear regression analysis (r=0.33). Vp and EDS discriminated poorly between normal and highly abnormal diastolic function. CONCLUSIONS: Vp and EDS were significantly related to diastolic function by traditional Doppler evaluation. They were, however, not useful as single parameters of left ventricular diastolic function due to a small difference between normal and highly abnormal values, allowing for little between-measurement variability. Consequently, these methods for the evaluation of left ventricular diastolic function do not add significantly to traditional Doppler evaluation.

Left ventricular remodelling and dysfunction. Can the process be prevented?

Due to continuous remodelling myocardial dysfunction is a progressive condition. Even if the initial event is so mild that it causes no immediate cardiac dysfunction (e.g. a small myocardial infarction), the remodelling process is triggered. Although the remodelling process can be adaptive, the process becomes maladaptive when the stimuli are continuous and pathological. A similar remodelling process is seen in most primary myocardial disorders, suggesting common mechanisms for the development of heart failure. Although clinical heart failure may develop acutely, for example, after an acute myocardial infarction, the progressive changes in myocardial structure and deterioration of myocardial function can go on silently for a very long time and overt heart failure may develop several years after an initial insult, even if there are no further events. In order to fundamentally improve prognosis in cardiac failure it is necessary to identify patients with an ongoing remodelling process and to effectively counteract this process as early as possible.

Health-related quality of life in elderly patients with heart failure.

OBJECTIVE: To assess health-related quality of life (HRQL) in elderly patients with congestive heart failure (CHF) and correlate these to clinical and demographic variables. PATIENTS AND METHODS: HRQL was evaluated in 191 patients with CHF, aged 65-84 years, using a self-administered questionnaire including the Nottingham Health Profile (NHP), Quality of Life Questionnaire in Heart Failure and Patients' Global Self-Assessment. RESULTS: HRQL was more impaired in women than to men (p < 0.05), New York Heart Association functional class correlated to HRQL (p < 0.01) and HRQL, as assessed by NHP, was impaired in CHF patients compared to a previously evaluated, age and sex matched, normal reference population. CONCLUSION: Measurement of HRQL in heart failure patients provides important information in addition to a clinical evaluation, and inclusion of HRQL assessments in clinical practice is feasible and warranted. Specific intervention should be aimed at improving HRQL in those most severely affected.