The use of bone marrow cells (BMCs) in therapeutic angiogenesis has been studied extensively. However, the critical paracrine effects of this treatment are still unclear. Therefore, we studied autotransfusable cells that produce vascular endothelial growth factor (VEGF), especially VEGF-C.Male C57BL/6 mice with hind limb ischemia were administered intramuscular injections of phosphate-buffered saline as controls, or unsorted BMCs, sorted CD11b+, or CD11b− cells from BMCs, and recombinant VEGF-C. To evaluate the treatments, perfusion was measured by laser Doppler scanning performed on days 0, 1, 3, 7, 14, 21, and 28. A functional assay was performed in parallel, with mice traversing an enclosed walkway. Capillary density was determined by directly counting vessels stained positive with von Willebrand factor at individual time points. Lymphangiogenesis was assessed by LYVE-1 positive cells.Postischemic recovery of hind limb perfusion significantly improved in BMC, CD11b+, and VEGF-C treatment groups compared with the control groups, as assessed by laser Doppler scanning. On early operative days 1 and 3, the blood flow recovery ratio was higher in the CD11b+-treated group compared with BMC and VEGF-C treatment groups. In the functional assay, the VEGF-C group dramatically recovered compared with the control group. The capillary/myofiber ratio in the thigh muscle and number of LYVE-1 positive cells was higher in the CD11b+ and VEGF-C groups than in controls. Furthermore, expression of VEGF-A, VEGF-C, and VEGF receptor messenger ribonucleic acid and protein was observed in CD11b+ cells.The VEGF-C derived from CD11b+ cells play a critical role in angiogenesis and lymphangiogenesis in a murine model of hind limb ischemia. Consequently, treatment with self-CD11b+ cells accelerated recovery from ischemia and may be a promising therapeutic strategy for peripheral arterial disease patients.

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.

Primary hyperparathyroidism (pHPT), caused by solitary parathyroid adenomas in 85% of cases and diffuse hyperplasia in most of the remaining cases, overproduces parathyroid hormone (PTH), which mobilizes calcium to the blood stream. Renal stones, osteoporosis and diffuse symptoms of hypercalcaemia, such as constipation, fatigue and weakness are well-known complications. However, in Western Europe and North America, patients with pHPT are nowadays usually discovered during an early, asymptomatic phase of the disease. It has been reported that patients suffering from symptomatic pHPT have increased mortality, mainly due to an overrepresentation of cardiovascular death. pHPT is reported to be associated with hypertension, disturbances in the renin—angiotensin—aldosterone system, and structural and functional alterations in the vascular wall. Recently, studies have indicated an association between pHPT and heart disease, and studies in vitro have produced a number of theoretical approaches. An increased prevalence of cardiac structural abnormalities such as left ventricular hypertrophy (LVH) and valvular and myocardial calcification has been observed. Associations have been found between PTH and LVH, and between LVH and serum calcium. LV systolic function does not seem to be affected in patients with pHPT, whereas any influence on LV diastolic performance needs further evaluation. The aim of this review is to clarify the connection between pHPT and cardiac disease.

BACKGROUND:Simpson ejection fraction, wall motion score index, atrioventricular (AV) plane displacement and fractional shortening are all established formal echocardiographic methods for the assessment of left ventricular systolic function. Visually estimated (eyeballing) ejection fraction may be considered somewhat more subjective, although shown to correlate well with radionuclide ventriculography. We aimed to explore if echocardiographic eyeballing ejection fraction is comparable to formal methods for the evaluation of left ventricular systolic function.METHODS:We assessed 89 consecutive patients after myocardial infarction or before coronary angiography. Eyeballing ejection fraction and wall motion score index were evaluated in the long-axis, short-axis and apical four- and two-chamber views. Simpson ejection fraction and AV plane displacement were assessed in the apical views. Fractional shortening was measured in the parasternal long-axis view. The respective systolic function measurements were in each patient made at different time points by a single investigator, masked to prior results.RESULTS:All formal methods correlated significantly with eyeballing ejection fraction (p<0.001): AV plane displacement, R=0.647; FS, R=0.684; four-chamber Simpson ejection fraction, R=0.857; biplane Simpson ejection fraction, R=0.898; and wall motion score index, R=0.919.CONCLUSION:Eyeballing ejection fraction correlated closely with all formal methods and the correlation coefficient improved with the reliability of the formal method. This finding is in concordance with prior studies, indicating that eyeballing ejection fraction may be the most accurate echocardiographic method for the assessment of left ventricular systolic function. Since it is readily and quickly performed, eyeballing ejection fraction could be used for routine echocardiography instead of formal methods.

Aim: The aim of the present study was to investigate if left atrioventricular plane displacement (AVPD) has a prognostic value in patients with atrial fibrillation. Methods and results: Left AVPD was assessed by two-dimensionally guided M-mode echocardiography in the four- and two-chamber views in 160 consecutive patients with chronic atrial fibrillation, who were followed up with regard to mortality for an average of 45 months. All-cause mortality during follow-up was 49% (n=78). AVPD was lower in patients who died compared to those who survived: 6.6+/-1.7 versus 7.5+/-1.7 mm, P=0.0005. In 49 patients (31%), death was due to chronic heart failure or acute myocardial infarction. Among those who died of cardiac events, AVPD was 6.3+/-1.6 mm, versus 7.1+/-1.8 mm among those who died of other causes, P=0.0001. In multiple logistic regression analysis, AVPD (P=0.005), age (P=0.0005), and a history of chronic heart failure (P=0.004) correlated independently with mortality. Conclusion: Left AVPD was clearly decreased in patients with atrial fibrillation. The decrease was most pronounced in patients who died of cardiac events, whereas it did not differ significantly between those who died of non-cardiac causes and those who survived. The discriminative value of left AVPD was limited. (C) 2003 Elsevier Ireland Ltd. All rights reserved.

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.

Aim: We aimed to find out if abnormal left atrioventricular plane displacement (AVPD) is a sign of myocardial dysfunction, even in patients with normal left ventricular (LV) regional wall motion (RWM). Methods: We prospectively performed echocardiography in 1350 consecutive patients referred to our echocardiography laboratory. Left AVPD and LV RWM were evaluated in all patients. We prospectively selected all patients with normal LV RWM but impaired left AVPD for further analysis of clinical parameters. Results: Eighty-eight of the 1350 patients had completely normal LV RWM but impaired left AVPD (≤10 mm) in at least one region (septal, lateral, posterior, anterior). Of these, 60.2% had prior and/or acute myocardial infarction, predominantly non-Q-wave, whereas 33.0% had angina without infarction and 2.3% had hypertension. In 49 (55.7%) patients coronary angiography was performed. All were abnormal. In 4.5% (n = 4) of the patients no obvious reason for the AVPD decrease was found, but was not precluded. Conclusion: Almost all patients with abnormal left AVPD and completely normal LV RWM had clinical cardiac disease. Thus, decreased AVPD despite normal LV RWM seems to be a true sign of myocardial dysfunction, predominantly indicating subendocardial dysfunction. In screening for patients with myocardial dysfunction assessment of left AVPD may be useful as a complement to LV RWM evaluation. The prognosis in such patients is currently being evaluated.

Although a cornerstone in the treatment of heart failure, angiotensin-converting enzyme inhibitors are under-used, partly due to side effects. If proven at least similarly efficacious to angiotensin-converting enzyme inhibitors, angiotensin-receptor blockers may replace them due to their superior tolerability. We aimed to compare the efficacy and safety of valsartan and enalapril in heart failure patients stabilised on an angiotensin-converting enzyme inhibitor. We randomised 141 patients (mean 68 years, 74% males) with stable mild/moderate heart failure and left ventricular ejection fraction 0.45 or less, to valsartan 160 mg q.d. (n=70) or enalapril 10 mg b.i.d. (n=71) for 12 weeks. Changes in 6-min-walk test (primary efficacy variable), patients' wellbeing and left ventricular size and function did not differ significantly between the treatment groups. Valsartan was significantly non-inferior to enalapril in walk test distance change: least-square means treatment difference +1.12 m (95% confidence interval -21.9 to 24.1), non-inferiority P<0.001. Left ventricular size (P<0.001) and function (P=0.048) improved significantly only in the valsartan group. Fewer patients experienced adverse events in the valsartan group (50%) than in the enalapril group (63%), although statistically non-significant. Valsartan is similarly efficacious and safe to enalapril in patients with stable, mild/moderate heart failure, previously stabilised on an angiotensin-converting enzyme inhibitor and directly switched to study medication.

AimsThe relation between abnormal left ventricular (LV) diastolic filling and the extent of coronary atherosclerosis per se has not been described. We aimed to investigate the prevalence of impaired LV diastolic filling in patients with stable coronary artery disease (CAD) and its relationship to the number and location of coronary lesions visualized at coronary angiography. Methods and resultsIn 170 consecutive patients with stable CAD and an abnormal coronary angiogram we assessed LV diastolic filling by Doppler evaluation of the transmitral early to atrial peak flow velocity (E/A) and the systolic to diastolic ratio of the pulmonary venous peak inflow to the left atrium (S/D). Abnormal diastolic filling was defined as E/A ≤0.75, or E/A >1.0 combined with S/D ≤1.0, and was present in 41% of the patients. In patients with one-, two- and three-vessel disease the prevalence of impaired diastolic filling was 27, 30 and 49%, respectively (P  = 0.026). In multiple logistic regression analysis diastolic filling was independently correlated with the number of stenotic coronary vessel areas. ConclusionIn patients with stable angiographically verified CAD, the prevalence of impaired diastolic filling was 41%. The prevalence increased with an increasing number of stenotic coronary artery areas independent of other variables tested, including prior myocardial infarction, LV systolic function and mitral regurgitation.

Background: Mean left atrioventricular plane displacement is strongly related to prognosis in patients with heart failure. We aimed to examine its value for prognostication and risk stratification in patients hospitalised for acute myocardial infarction. Methods and results: Left atrioventricular plane displacement was assessed by echocardiography in 271 consecutive patients with acute myocardial infarction. Mean prospective follow-up was 628 days. Atrioventricular plane displacement was readily assessed in all patients and was significantly lower in patients who died (n=41, 15.1%) compared to the survivors: 8.2(5.6) v. 10.0(5.5) mm, P<0.0001. Overall mortality was 31.3% in the lowest quartile with regard to atrioventricular plane displacement (<8.00 mm) and 10.1% in the combined upper three quartiles. Thus, the hazard ratio for an atrioventricular plane displacement <8.0 mm compared to 8 mm or more was 3.1, P=0.0001. The combined mortality/heart failure hospitalisation incidence was 43.8% in the lowest and 14.6% in the combined upper three quartiles: Risk ratio 3.0, P<0.0001. In multivariate analysis, including age and history of atrial fibrillation, left atrioventricular plane displacement was an independent prognostic marker. Conclusion: In post-myocardial infarction patients, echocardiographic assessment of atrioventricular plane displacement showed a strong, independent prognostic value. Determination of left atrioventricular plane displacement can be readily performed in virtually all patients, and may in clinical practice facilitate identification of high-risk patients.

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.

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.