Background: Stroke volume (SV) and aortic valve area calculations require the left ventricular (LV) outflow tract (LVOT) or aortic annular area calculations that involve squaring the respective diameters. Area calculation errors became evident with transcatheter aortic valve replacement where areas were underestimated due to an elliptical annulus. We hypothesized that LVOT and annular shape are more elliptical in patients with greater relative LV wall thickness (RWT) leading to underestimation of SV index using 2D Doppler echocardiography. Methods: We studied 203 consecutive patients referred to an outpatient noninvasive laboratory for Doppler echocardiograms which included acceptable 3-dimensional images. 3-dimensional assessment of the LVOT at 3–5 mm from the valve insertion, at the site of valve insertion, and at the sinus of Valsalva (SOV) was performed with assessment of the minor axis (MN), major axis (MJ), and areas at mid-systole. SV index was calculated from LVOT and annular diameters obtained from 2-dimensional echo and from 3-dimensional LVOT areas. Results: An inverse relation of RWT with MN/MJ at mid-systole for the LVOT (r = 0.5812, P < 0.0001) and annulus (r = 0.6865, P < 0.0001) was noted. LVOT and annulus areas were similar among groups at mid-systole. SV index calculated from 2D LVOT dimensions was significantly smaller than using 3D LVOT areas (35.6 ± 8.9 vs 53.6 ± 16.1 mL, P < 0.0001). Conclusion: There is an inverse relation between MN/MJ and RWT at the LVOT and aortic annulus despite the LVOT and annular areas being similar across most geometries resulting in SV index underestimation calculated using LVOT diameters vs 3D LVOT areas.

Left ventricular hypertrophy (LVH), the detection of which is recommended for routine risk prediction by all guidelines, is more prevalent in groups of African ancestry. This is in-part attributed to higher prevalence rates of obesity. The ability to detect LVH using electrocardiographic (ECG) criteria may be modified in groups of African ancestry. The impact of co-existent obesity on the ability to detect ECG-LVH in this ethnic group has not been determined. Moreover, whether estimated glomerular filtration rate (eGFR) or serum C-reactive protein (CRP concentrations are independently associated with LV mass index (LVMI) and can therefore be used to complement ECG criteria for LVH detection is uncertain. ECG voltage criteria for the detection of echocardiographic LVH were evaluated in 661 participants from a community sample of African ancestry (43% obese). Body mass index (BMI) was inversely associated with Sokolow-Lyon (SL) voltages (partial r=-0.27, p<0.0001) and no BMI-Cornell voltage relations were noted (p=0.21). BMI was associated with voltage criteria that incorporate only limb lead recordings (r=0.17-0.23), but these relationships were weaker than BMI-LVMI relations (r=0.36, p<0.01-p<0.0001 for comparisons of r values). All ECG criteria were as strongly related to blood pressure (BP) as LVMI. Sokolow-Lyon voltage-LVMI relations were noted only after adjustments for BMI (p<0.02) and SL voltages showed no performance for LVH detection. Cornell voltages showed significant performance in the non-obese (area under the receiver operating curve [AUC]=0.67±0.04, p<0.0005), but not the obese (AUC=0.56±0.04, p=0.08). ECG criteria which employ limb-lead recordings only (e.g. RaVL) showed better performance in non-obese than obese (AUC=0.75±0.04 and 0.59±0.04 respectively, p<0.005 for comparison) and markedly reduced specificity for LVH detection in obese (76%) than non-obese (92%, p<0.0001) despite similar sensitivities (32 vs 29%). Thus, in groups of African ancestry, obesity contributes toward a poor validity and performance of all voltage criteria for the detection of LVH. None of the current criteria are recommended for use in obesity in groups of African descent. Alternative approaches are required for LVH detection in these groups.In 621 randomly selected participants from the community sample [332 were normotensive (NT)], eGFR was associated with LVMI and LVM in excess of that predicted from stroke work (inappropriate LVM, LVMinappr) in all participants (LVMI: partial r=-0.18, p<0.0001; LVMinappr: partial r=-0.17, p<0.0001) and NT (LVMI: partial r=-0.23,p<0.0001; LVMinappr: partial r=-0.22, p<0.0001) separate from hypertensives. When replacing clinic BP with either aortic systolic BP (applanation tonometry and SphygmoCor software), 24-hour BP, aortic pulse wave velocity (PWV) (applanation tonometry and SphygmoCor software), stroke work (for LVMI), LV end diastolic diameter (LVEDD), or circumferential wall stress in the regression models, eGFR retained strong associations with LVMI (p=0.01 to <0.0001) and LVMinappr (p<0.005 to <0.0001). Thus, strong relationships between eGFR and LVM occur at a community level irrespective of the presence of hypertension and independent of 24-hour and aortic BP, PWV, LVEDD,stroke work and wall stress. The independent relationships between eGFR and LVMI, support the notion that eGFR may be evaluated for LVH detection. In 361 randomly selected participants from a community with a high prevalence of CRP concentrations considered to be high-risk (54.0%), but without cardiovascular or renal disease, serum CRP concentrations were correlated with both LVMI and LVMinappr (p<0.0001). With adjustments for a number of potential confounders including age, systolic BP, waist circumference (or BMI), and glucose control (glycated haemoglobin), the relationships between serum CRP concentrations and both LVMI and LVMinappr (partial r=0.11, p<0.05 for both) persisted. The independent relationship between CRP and LVMI or LVMinappr translated into a higher multivariate-adjusted LVMI and LVMinappr values in the highest as compared to the lowest quartile of CRP (LVMI; highest quartile CRP=48.8±10.7, lowest quartile CRP=45.0±11, p<0.05; LVMinappr; highest quartile CRP=137±24, lowest quartile CRP=127±24, p<0.05). The independent relationships between CRP and LVMI, support the notion that CRP may also be evaluated for LVH detection. In 358 participants from a randomly selected community sample with a high prevalence of obesity (41%), a combination of CRP concentrations and eGFR above or below the median for the sample respectively showed significant performance (AUC=0.61±0.03, p<0.0005), but a low specificity for LVH detection (77%). When eGFR and CRP concentrations were employed to complement RaVL, although the overall performance did not improve (AUC=0.71±0.03, p<0.0005, RaVL alone: AUC=0.70±0.03), the specificity increased (93%) whilst sensitivity (25%) was in-line with previously reported sensitivities for LVH detection using ECG criteria in alternative population samples. Without changing overall performance, eGFR together with RaVL increased the specificity to 88% and CRP concentrations when considered together with RaVL increased the specificity to 87%. Thus, in a community sample where the specificity and performance of ECG criteria for LVH detection are poor, the use of eGFR and/or CRP concentrations to complement ECG criteria increase the specificity without altering the overall performance. In conclusion, the present thesis provides evidence to indicate that current ECG criteria for the detection of LVH are invalid in obese individuals of African ancestry, but that clinical markers of renal dysfunction and systemic inflammation, which are associated with LVMI independent of haemodynamic factors and co-morbidities may be employed to complement ECG criteria to improve the specificity for LVH detection.

Left ventricular hypertrophy (LVH) and increases in large artery stiffness predict cardiovascular outcomes in patients with renal failure. What determines left ventricular mass index (LVMI) and large artery stiffness and the contribution toward LVH and large artery dysfunction is not entirely clear. Consequently, this cross sectional study was aimed at assessing the various factors impacting on LVH in haemodialysis (HD), to contribute toward our understanding of the pathophysiology of LVH and large artery dysfunction in 94 adult HD patients. Pre- and post-dialysis blood pressures (BPs) were determined over 12 sessions of dialysis and averaged. Pulse wave analysis performed at the carotid, femoral and radial arteries was employed to determine pulse wave velocity (PWV) and central augmentation index (AIc). Echocardiography was performed to determine left ventricular mass (LVM) indexed to body surface area (LVMI). Natriuretic peptides, procollagen type I c-peptide (PIP), c-terminal telopeptide of type I collagen (ICTP), matrix metalloproteinases and their inhibitors were studied. The prevalence of LVH was 72.8 % (67/92) .On multivariate analysis pre- (p≤ 0.005), post- (p<0.05) and averaged dialysis (p < 0.015) systolic BP were associated with LVMI and PWV. 24 hour (r = 0.260, p = 0.026), day (r = 0.247, p = 0.036), and night (r= 0.241, p = 0.042) systolic BP were not more closely associated with LVMI than the averaged dialysis systolic BP (r = 0.272, p = 0.010). Similarly 24 hour (r = 0.41, p = 0.0003), day (r=0.400, p = 0.0005), and night (r =0.416, p = 0.0003) systolic BP were not more closely associated with PWV than the post-dialysis systolic BP (r=0.39, p=0.0001) indicating that these BP measurements are as effective as 24-hour ambulatory BP in predicting cardiovascular target organ changes. No relationship between either PWV (r=-0.08), or AIc (r=-0.10) and LVMI, between PWV (r=-0.11), or AIc (r=0.03) and LV MWT was noted. IVCD was independently associated with LVMI (partial r adjusted for average dialysis SBP=0.27, p=0.014; partial r adjusted for 24-hour SBP=0.29, p=0.013), and LV mean wall thickness (p<0.01), but not with LV relative wall thickness (p=0.18), or LV end diastolic diameter (p=0.88). An association between IVCD and AIc (partial r adjusted for average dialysis SBP=0.21, p<0.05), but not PWV was noted. NT-proANP and NT-proBNP were independently associated with LVMI (p<0.0001) but neither were associated with IVCD independent of LVMI suggesting a close association with LVMI in HD. Serum concentrations of matrix metalloproteinases 1, 2 and 9, and their tissue inhibitors (1 and 2) were not associated with LVMI, remodelling or PWV and neither procollagen I nor the C-terminal telopeptide of type I collagen (ICTP) were associated with LVMI. Thus, factors impacting on LVH in this study were systolic BP, NT-proANP, NT-proBNP and IVCD.

Diss. (sammanfattning) Uppsala : Univ., 2001. / Härtill 5 uppsatser.

Thesis (M.A.)--Boston University

Left ventricular hypertrophy (LVH) is more frequently associated with LV dilatation and systolic chamber dysfunction in males than in females. The mechanisms of this effect are uncertain. As excessive adrenergic stimulation may be responsible for LV dilatation and systolic chamber dysfunction in hypertension, in my dissertation I aimed to assess whether gender determines the adverse effects on LV chamber remodeling following 6 months of daily β-adrenergic receptor (AR) stimulation (isoproterenol [ISO] at 0.04 mg.kg-1day-1) in spontaneously hypertensive rats (SHR). LV dilatation was assessed in vivo from LV end diastolic diameter (EDD) (echocardiography) and ex vivo from the volume intercept at 0 mm Hg pressure (V0) of the LV diastolic pressure-volume relationship (isolated, perfused heart technique). LV systolic function was determined in vivo from LV endocardial fractional shortening (FSend) and ex vivo from the slope (LV end systolic elastance [LV Ees]) of the LV end systolic pressure-volume relationship (isolated, perfused heart technique). As compared to saline-treated male SHR (n=13), male SHR receiving ISO for 6 months (n=13) developed an increased LV EDD (Male Saline: 6.56±0.20 mm; Male ISO: 7.78±0.29 mm; p<0.05) and LV V0 (Male Saline: 0.22±0.01 ml; Male ISO: 0.31±0.02 ml; p<0.05). In contrast, ISO administration failed to modify LV EDD (Female Saline, n=13: 6.06±0.15 mm; Female ISO, n=12: 6.33±0.15 mm) or LV V0 (Female Saline: 0.17±0.01ml; Female ISO: 0.17±0.01 ml) in female SHR. In addition, there was a gender-ISO interactive effect on LV Ees (p<0.05; Male Saline: 2268±336 mmHg.ml-1; Male ISO: 1623±164 mmHg.ml-1; Female Saline: 1910±219 mmHg.ml-1; Female ISO: 2302±230 mmHg.ml-1). In conclusion, as compared to female SHR, male SHR are more susceptible to the adverse effects of chronic β-AR activation on LV cavity dimensions and systolic chamber function. These results suggest that the higher prevalence of LV dilatation and systolic chamber dysfunction in males than in females with LVH may be attributed to an increased susceptibility to the adverse effects of adrenergic stimulation.

<p>Knowledge of the leftventricular (LV) pressure-volume relation, along withparameters derived from this relation, have led to newpossibilities for the characterisation of cardiac pumpfunction, in both experimental studies and clinicalsettings.</p><p>The pressure-volume diagram is apowerful tool for visualising LV performance, but in order tobe clinically useful it is necessary to make plots continuouslyand on-line. The conductance catheter technique offers thispossibility. The conductance catheter system has experiencedgrowing interest among cardiologists, physiologists, surgeons,and anaesthesiologists around the world as a powerful newresearch tool, but the invasiveness of this technique has beena limiting factor for most clinical applications. The catheterneeds to be thinner and softer in order to make this techniquemore suitable for human use.</p><p>This thesis reports of a newthin and soft conductance catheter for continuously and on-linemeasurements of LV pressure and volume.</p><p>One way to reduce both cathetersize and stiffness is to decrease the number of electrodes onthe catheter. Theoretical calculations shown in this thesisproves that it is possible to obtain the same performance witha single segment catheter as with a five-segment catheter. Thethin catheter has been tested and compared to a commercialfive-segment conductance catheter in animal studies.</p><p>We conclude that the thin singlesegment conductance catheter can measure left ventricularvolume and pessure. The regression coefficient between the twomethods is good independent of loading condition and duringbaseline conditions the catheters produce very similar volumecurves. During preload reduction the estimated volume reductionis different in the two systems.</p><p>Our thin catheter does notdisturb the heart's normal electrophysiology, neither by thecatheter current nor by any mechanical stimuli. The resultsdemonstrates that our thin, soft, single segment conductancecatheter has performance characteristics which warrant furtherdevelopment, with the goal to make the method available forhuman use.</p>

Knowledge of the leftventricular (LV) pressure-volume relation, along withparameters derived from this relation, have led to newpossibilities for the characterisation of cardiac pumpfunction, in both experimental studies and clinicalsettings. The pressure-volume diagram is apowerful tool for visualising LV performance, but in order tobe clinically useful it is necessary to make plots continuouslyand on-line. The conductance catheter technique offers thispossibility. The conductance catheter system has experiencedgrowing interest among cardiologists, physiologists, surgeons,and anaesthesiologists around the world as a powerful newresearch tool, but the invasiveness of this technique has beena limiting factor for most clinical applications. The catheterneeds to be thinner and softer in order to make this techniquemore suitable for human use. This thesis reports of a newthin and soft conductance catheter for continuously and on-linemeasurements of LV pressure and volume. One way to reduce both cathetersize and stiffness is to decrease the number of electrodes onthe catheter. Theoretical calculations shown in this thesisproves that it is possible to obtain the same performance witha single segment catheter as with a five-segment catheter. Thethin catheter has been tested and compared to a commercialfive-segment conductance catheter in animal studies. We conclude that the thin singlesegment conductance catheter can measure left ventricularvolume and pessure. The regression coefficient between the twomethods is good independent of loading condition and duringbaseline conditions the catheters produce very similar volumecurves. During preload reduction the estimated volume reductionis different in the two systems. Our thin catheter does notdisturb the heart's normal electrophysiology, neither by thecatheter current nor by any mechanical stimuli. The resultsdemonstrates that our thin, soft, single segment conductancecatheter has performance characteristics which warrant furtherdevelopment, with the goal to make the method available forhuman use. / NR 20140805

ABSTRACT There is substantial evidence to suggest that independent of conventional BP, LV mass (LVM) is higher in African-Americans than in European-Americans a difference that may translate into a higher prevalence of cardiovascular diseases. In the present thesis I assessed whether LVM is similarly elevated in groups of African descent living in Africa, and subsequently whether 24-hour, day or night BP or indices of arterial stiffness could explain the variability in LVM beyond conventional BP in this population group. As there is considerable controversy as to whether 24-hour BP measurements are better predictors of the regression of LVH than conventional BP and whether antihypertensive agents that target the renin-angiotensin system (RAS) regress LV hypertrophy (LVH) independent of BP in groups of African descent, in the present thesis I therefore also assessed these questions. In 141 healthy adult participants obtained from a random sample of nuclear families (n=399) of African ancestry living in Soweto, I determined that LVM adjusted for body surface area to the first power was an appropriate allometric signal to account for growth effects on LVM. The allometric signals established in other populations considerably over-adjusted for LVM in the group that I studied with marked negative relations noted. After adjusting for body surface area I noted upper thresholds of LVM index (LVMI) of 134 g/m2 for men and 112 g/m2 for women. As compared to thresholds described for other population samples these thresholds were noted to be modestly higher. In 187 women from randomly recruited nuclear families of African ancestry, after appropriate adjustments, conventional BP was as closely associated with LVMI as 24- hour BP, and daytime BP was as closely associated with LVMI as night-time BP in women. However, in 110 men from randomly recruited nuclear families of African ancestry, after appropriate adjustments, only night-time BP was associated with LVMI, an effect that was independent of conventional BP (r=0.21, p<0.05). Indices of nocturnal decreases in BP were not associated with LVMI in either gender group. Furthermore, in randomly recruited nuclear families of African ancestry, after appropriate adjustments, including systolic BP or pulse pressure, pulse wave velocity (an index of arterial stiffness assessed using applanation tonometry) was independently associated with LVMI in women (n=204, r=0.25, p<0.0005), but not in men (n=123, r=-0.07). In 173 hypertensive patients of African descent of whom 64 were previously untreated and 109 were previously treated, I assessed whether ambulatory BP is a better predictor of on-treatment decreases in LVMI over a 4 month treatment period. In the previously untreated patients, the regression in LVMI correlated to a similar degree (p<0.09) with decreases in conventional (r=0.34; p<0.005) and 24-hour (r=0.26; p<0.04) systolic BP. In this same study sample followed prospectively for 25 months, accounting for effects on ambulatory BP at each time point, the use of the angiotensin-converting enzyme inhibitor, enalapril, was not associated with LVMI, whereas, on-treatment conventional systolic BP (p=0.01) and night-time systolic BP (p=0.01) were associated with LVMI. In a further study conducted in 87 patients of African ancestry with hypertension and LVH, I showed that changes in systolic ambulatory BP (daytime, r=0.46, p=0.006) were predictive of changes in LVMI after 2 months of treatment with an angiotensin II receptor blocker (candesartan), ACE-I (ramipril) and the diuretic agent, hydrochlorothiazide. Moreover, in a final study I showed that in hypertensive patients of African ancestry, initiating therapy with the diuretic, indapamide SR and then adding the ACE-I, perindopril 4 mg (n=42), was equally as effective as amlodipine (calcium channel blocker) (n=44) therapy at reducing ambulatory BP and LVMI. Thus, in conclusion, groups of African descent living in Africa have only marginally higher thresholds for LVM than other population groups. Moreover, in this population group, nocturnal BP has a conventional BP-independent effect on LVMI in men, but not in women, whereas arterial stiffness has a conventional BP-independent effect on LVMI in women, but not in men. Further, in this population, reductions in LVM produced by antihypertensive therapy appear to be equally as closely related to conventional as ambulatory BP and in contrast to findings in groups of European ancestry, where RAS blockers produce unique benefits on LVM beyond conventional BP reductions, in groups of African ancestry in Africa, RAS blockers produce no BPindependent reductions in LVM. Moreover, in this population, decreases in LVM in patients with LVH produced by RAS blockers are related to ambulatory BP changes and despite the ineffectiveness of RAS blockers on BP when used as monotherapy in this population, RAS blockers together with diuretics are equally as effective in decreasing BP and LVM as compared to a class of antihypertensive agents with established efficacy (calcium channel blockers). Hence when compelling indications for RAS blockade exist, RAS blocker-diuretic combinations are effective therapy in patients of African descent living in Africa.

No description available.