CLINICAL STUDY: DIASTOLIC DYSFUNCTION
The impact of diabetes on left ventricular filling pattern in normotensive and hypertensive adults: the strong heart study
Jennifer E. Liu, MD*,
Vittorio Palmieri, MD*,
Mary J. Roman, MD, FACC*,
Jonanthan N. Bella, MD*,
Richard Fabsitz, MA ,
Barbara V. Howard, PhD ,
Thomas K. Welty, MD, MPH ,
Elisa T. Lee, PhD|| and
Richard B. Devereux, MD, FACC*
* Department of Medicine, the New York Hospital-Cornell Medical Center, New York, New York, USA
National Heart Lung and Blood Institute, Bethesda, Maryland, USA
Medstar Research Institute, Washington, D.C, USA
Aberdeen Area Tribal Chairmen’s Health Board, Rapid City, South Dakota, USA
|| School of Public Health, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, USA
Manuscript received August 30, 2000;
revised manuscript received January 23, 2001,
accepted February 6, 2001.
Reprint requests and correspondence: Dr. Jennifer E. Liu, Division of Cardiology, Box 222, The New York Presbyterian Hospital-Weill Cornell Medical Center, 525 East 68th Street, New York, New York 10021
jeliu{at}med.cornell.edu
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Abstract
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OBJECTIVES
We sought to determine the effect of diabetes mellitus (DM) on left ventricular (LV) filling pattern in normotensive (NT) and hypertensive (HTN) individuals.
BACKGROUND
Diastolic abnormalities have been extensively described in HTN but are less well characterized in DM, which frequently coexists with HTN.
METHODS
We analyzed the transmitral inflow velocity profile at the mitral annulus in four groups from the Strong Heart Study: NT-non-DM (n = 730), HTN-non-DM (n = 394), NT-DM (n = 616) and HTN-DM (n = 671). The DM subjects were further divided into those with normal filling pattern (n = 107) and those with abnormal relaxation (AbnREL) (n = 447).
RESULTS
The peak E velocity was lowest in HTN-DM, intermediate in NT-DM and HT-non-DM and highest in the NT-non-DM group (p < 0.001), with a reverse trend seen for peak A velocity (p < 0.001). In multivariate analysis, E/A ratio was lowest in HTN-DM and highest in NT-non-DM, with no difference between NT-DM and HTN-non DM (p < 0.001). Likewise, mean atrial filling fraction and deceleration time were highest in HTN-DM, followed by HTN-non-DM or NT-DM and lowest in NT-non-DM (both p < 0.05). Among DM subjects, those with AbnREL had higher fasting glucose (p = 0.03) and hemoglobin A1C (p = 0.04).
CONCLUSIONS
Diabetes mellitus, especially with worse glycemic control, is independently associated with abnormal LV relaxation. The severity of abnormal LV relaxation is similar to the well-known impaired relaxation associated with HTN. The combination of DM and HTN has more severe abnormal LV relaxation than groups with either condition alone. In addition, AbnREL in DM is associated with worse glycemic control.
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Abbreviations and Acronyms
| | AGES | = advanced-glycated end products | | CESS | = circumferential end-systolic stress | | DM | = diabetes mellitus | | DT | = deceleration time | | HTN | = hypertension | | LV | = left ventricular | | NT | = normotensive | | SBP | = systolic blood pressure | | SHS | = Strong Heart Study |
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Diabetes mellitus (DM) is an established risk factor for cardiovascular events (1,2), especially the development of congestive heart failure (3). It has been suggested that impairment of left ventricular (LV) function in patients with DM is due to concomitant risk factors such as arterial hypertension (HTN) or to diffuse peripheral and coronary atherosclerosis (4,5). However, actual mechanisms remain unclear and evidence has accumulated for the existence of a distinct diabetic cardiomyopathy (6).
Impairment of LV diastole in patients with DM filling has been described using digitized M-mode and Doppler echocardiography (7,8). However, previous reports of the association of diastolic abnormalities with DM did not take into account confounding factors such as HTN, increased LV mass and abnormal systolic function, which frequently coexist with DM (9–11). Furthermore, the relationship of glucose control to LV diastolic filling in DM has not been well defined. The present study was undertaken to determine the effect of DM on LV filling in normotensive and hypertensive adults using Doppler transmitral flow velocity profile, and to assess the relationship of glycemic control to diastolic function in the DM population.
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Methods
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The Strong Heart Study (SHS) is a population-based survey of cardiovascular risk factors and prevalent and incident cardiovascular disease in American Indian communities in Arizona, Oklahoma and South and North Dakota. The study was conducted by the University of Oklahoma with approval by the institutional committee on human research, the Indian Health Service and the tribe and was performed with the subjects’ written informed consent. As previously described (12–14), tribal members aged 45 to 74 years from three tribes in Arizona, seven tribes in southwestern Oklahoma and three communities in North/South Dakota were recruited from tribal members living on reservations or (in Oklahoma) in a defined geographic area (overall participation rate 62%) for an initial examination in from 1989 to 1992.
The second SHS examination was conducted from 1993 to 1995 to assess change over time in body habitus, blood pressure and most other baseline measures and to add echocardiography among surviving participants. A total of 3,630 surviving cohort members participated in the second SHS examinations, for an 89% return rate. Standardized measurements of seated brachial blood pressure; aspects of body habitus including body mass index, waist, hip ratio and percent body fat by bioelectric impedance; fasting glucose, insulin, lipid and lipoprotein concentrations; and 2-h glucose tolerance test and glycosylated hemoglobin levels were obtained. Diabetes was diagnosed by World Health Organization criteria (15) if fasting blood sugar was >140 mg/dl, 2-h post challenge glucose was >200 mg/dl or participants received hypoglycemic medication. Individuals with fasting sugar levels <140 mg/dl were divided into those with normal or impaired glucose tolerance depending on whether 2-h post-challenge glucose was < or  200 mg/dl. Duration of diabetes was based on patient reports. Participants were classified as hypertensive if blood pressure was 140 and/or 90 mm Hg or if participants were on antihypertensive drugs. Echocardiograms were performed in 3,501 participants (97%) in the second SHS examination. For the present study, SHS participants with normal glucose tolerance were compared with those with diabetes; individuals with impaired glucose tolerance were excluded to maximize the contrast between groups. Echocardiographic readers were blinded to participant clinical status.
Eligible participants in the second SHS examination were divided into four nonoverlapping groups: 1) 730 participants with neither hypertension nor diabetes (NT-non-DM); 2) 616 normotensive individuals with diabetes (NT-DM); 3) 394 hypertensive individuals without DM (HTN-non-DM); and 4) 671 hypertensive individuals with DM (HTN-DM). For some analyses, the DM subjects were further divided on the basis of diastolic filling pattern: normal filling pattern (E/A 1 and <2.0 and deceleration time [DT] 160 and <240 ms); abnormal relaxation (E/A< 1 and DT 240 ms); restrictive filling pattern (E/A >2 and DT <160 ms). Exclusion of individuals with prior definite myocardial infarction or coronary heart disease or segmental akinesis or dyskinesis did not affect study results. Subjects with ejection fraction <55% were excluded, as were those with suboptimal echocardiograms for LV mass or transmitral Doppler measurements, or with >2+ mitral or aortic regurgitation.
Echocardiographic methods.
Imaging and Doppler echocardiograms were performed using methods adapted from those employed in previous studies from the New York Presbyterian Hospital-Weill Cornell Medical Center echocardiography reading center. As previously described (16,17), studies were performed using phased-array echocardiographs with M-mode, two-dimensional, and pulsed continuous wave and color-flow Doppler capabilities. A standardized protocol was followed under which needed images and Doppler flow patterns were recorded 10 consecutive beats from appropriate acoustic windows (16,17).
Echocardiographic measurements.
Correct orientation of planes for imaging and Doppler recordings was verified as previously described (18). Measurements were made using a computerized review station equipped with digitizing tablet and monitor screen overlay for calibration and performance of each needed measurement. Left ventricular internal dimension and septal and posterior wall thicknesses were measured by American Society of Echocardiography recommendations (19) during up to three cardiac cycles. When optimal orientation of LV M-mode recordings could not be obtained, correctly oriented linear dimension measurements were made using two-dimensional imaging by the American Society of Echocardiography leading-edge convention (20).
To facilitate relating measurements of LV diastolic transmitral blood flow velocity to volume flow, the pulsed Doppler sample volume was placed at the middle of the mitral annulus, the diameter of which varies relatively modestly during the cardiac cycle, as opposed to the level of the leaflet tips where the mitral orifice shows substantial variation through the cardiac cycle. Participants were asked to hold their breath during pulse-wave Doppler interrogation. The leading edge of the transmitral Doppler flow pattern was traced to derive the peak of early diastolic and atrial-phase LV filling (E and A, respectively), their ratio, the deceleration time of early diastolic LV filling and the atrial filling fraction. Doppler measurements were performed offline from an average of several cardiac cycles. Heart rate was measured simultaneously.
Calculation of derived variable.
End-diastolic LV dimensions by the leading-edge convention were used to calculate LV mass by an adjusted cube-function formula that yields values closely correlated with necropsy LV weight (r = 0.90, p < 0.001) (21) and that showed good reproducibility (RHO = 0.93, p < 0.001) in a series of 183 hypertensive patients studied twice by echocardiography (22). Left ventricular mass measurements by this formula for M-mode or two-dimensional measurements have been shown in a series of 196 normotensive or hypertensive adults to be virtually interchangeable (r = 0.967, p < 0.001; mean difference = 0.4 ± 10.2 g, p = NS) (23). Left ventricular mass was normalized for body height2.7, where 2.7 is the power of the allometric or growth relation between LV mass and body height (24).
Measures of myocardial performance.
The primary approach to assess myocardial contractile efficiency was examination of LV systolic shortening in relation to end-systolic stress. Because the traditional practice of relating endocardial shortening to mean end-systolic stress across the LV wall may yield misleading results in individuals with either concentric geometry (25) or LV dilation (26), primary reliance was placed on the relation of midwall fractional shortening to midwall circumferential end-systolic stress measured at the level of the LV minor axis (25,27,28). Midwall shortening was calculated taking into account the epicardial migration of the midwall during systole. Circumferential end-systolic stress (cESS) was estimated at the midwall from M-mode tracings, using a cylindrical model (28). Observed midwall shortening was expressed as a percentage of the value predicted from cESS using equations derived from previously studied normal subjects (25). For convenience this variable is termed stress-corrected midwall shortening (23).
Statistical analyses.
Data were analyzed using SPSS 8.0 software (SPSS, Chicago, Illinois). Data are expressed as mean ± standard deviation. Differences between groups of participants were assessed by analysis of variance followed by the Scheffé post hoc test. Independence of differences from effects of covariates was assessed by single-factorial analysis of variance in the general linear model with Sidak’s post hoc test. A two-tailed p < 0.05 indicated statistical significance.
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Results
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Characteristics of participants (table 1).
The NT-non-DM participants were on average in late middle age, with normal mean heart rate and blood pressure. Compared with this reference group, HTN-non-DM participants were older, had similar heart rate and, partially by definition, higher systolic blood pressure (SBP). NT-DM participants were similar in age to the reference group but had higher heart rate and SBP. HTN-DM participants were older and had higher heart rate than the reference group. In addition, this group had higher SBP than the HTN-non-DM group. Fifty-nine percent of the HTN-non-DM group and 72% of the HTN-DM group were on antihypertensive treatment.
The HTN-DM group had the highest mean LV mass and LV mass/height2.7. The NT-DM group had higher mean LV mass and LV mass/height2.7 than the NT-non-DM group. However, LV mass and LV mass/height2.7 were higher in the HTN-non-DM than in the NT-DM group. Stress-corrected LV midwall shortening was lower in the groups with DM than in the NT-non-DM and HTN-non-DM groups.
Diastolic filling parameters (table 2).
Peak E velocity was lower in both NT-DM and HTN-DM groups than the NT-non-DM or HTN-non-DM groups. Peak A velocity was higher in the NT-DM group than the NT-non-DM group, but similar to the HTN-non-DM group and highest in the HTN-DM group. The E/A ratio showed a stepwise decrease from the NT-non-DM group to those with either condition to the combined HTN-DM group. The deceleration time of early diastolic transmitral flow was longer than in the NT-non-DM group by a mean of about 10 ms in the groups with either DM or HTN and by about 20 ms in the HTN-DM group. In addition, atrial filling fraction and first-half filling fraction were similar in the NT-DM and the HTN-non-DM groups, whereas the DM-HTN group had higher mean atrial filling fraction and lower mean first-half filling fraction than the other groups. To avoid underestimating the impact of hypertension and excessive load on diastolic filling parameters due to vasodilator therapy, a subanalysis was performed excluding participants on antihypertensive treatment. The results remained unchanged.
In analyses of covariance adjusting for age, gender, heart rate, LV mass and stress-corrected midwall shortening (Table 3), the mean E velocity was significantly lower in the groups with DM than in the NT-non-DM group. Mean A velocity was higher in groups with DM and/or HTN than in the reference group. As a result, the E/A ratio decreased stepwise from the NT-non-DM group to those with DM or HTN alone to lowest values in the group with both conditions. The deceleration time was longer in the DM- or HTN-alone groups than in the NT-non-DM group and was longest in the group with both conditions. Mean atrial filling fraction was slightly higher and the mean first-half filling fraction slightly lower in the NT-DM group than in the HTN-non-DM and NT-non-DM groups; both variables were, on average, more abnormal in the HTN-DM group.
Indices of DM control and diastolic filling.
Among the DM group, 330 participants had abnormal LV relaxation (E/A <1 and DT 240 ms) and 89 participants had normal filling pattern (1  E/A < 2 and 160 ms DT < 240 ms). The restrictive filling group was excluded from the analysis because of its small size (only seven DM subjects with E/A >2 and DT <160 ms). In multivariate analyses adjusting for age, heart rate, LV mass and stress-corrected midwall shortening, the abnormal relaxation group had higher fasting glucose, higher hemoglobin A1C levels and a trend towards longer reported duration of DM (Table 4). There was no difference in insulin levels. In addition, the abnormal relaxation group had a significantly higher urinary albumin/creatinine ratio.
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Discussion
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The present study represents the first comprehensive assessment of LV diastolic filling in adults with Type II DM in a population-based sample of middle-aged and older adults. The present study reveals an association between DM and abnormal early diastolic filling that is independent of age, arterial pressure, LV mass and systolic function. This association, as seen in the NT-DM group, is at least as strong as the well-known one of HTN with impaired early diastolic LV relaxation and filling. Concomitant DM further adds to the impairment of LV relaxation associated with HTN, as demonstrated by the finding that SHS participants with both DM and HTN had the most severely abnormal LV filling. Excluding the large percentage of the HTN groups who were on treatment in a subanalysis did not alter the results.
Diastolic LV filling patterns.
In our study of a population-based sample with a high prevalence of type 2 DM, the peak E velocity of early LV filling was lower in the NT-DM-alone group than in the reference group and lowest in the group with both conditions, independent of age, heart rate, LV mass and systolic function. Likewise, the ratios of early filling to atrial-augmented LV filling showed a stepwise decline from the NT-non-DM group to those with DM or HTN alone to the group with both DM and HTN. Parallel to these findings, previous studies have demonstrated a shift in LV filling from early relaxation phase to the late atrial phase in young type 1 diabetics (8,29–31).
Although the peak A velocity was higher in the group with HTN alone than in that with DM alone, the atrial filling fraction, which is less afterload-dependent, was higher in the DM-only group than in the HTN-only group or the reference group. Both peak A velocity and atrial filling fraction were highest in the combined HTN and DM group.
Diabetes and abnormal LV diastolic relaxation.
The association of diastolic filling abnormalities with DM in adults has been previously reported (7,32–34). However, our study is the first to confirm that this association is independent of other confounding variables that frequently coexist with DM. The abnormality of relaxation was more severe in the combined DM-HTN group than in the HTN-non-DM or NT-DM groups, suggesting additive deleterious effects on active LV relaxation in early diastole when both of these conditions are present.
Our study revealed that DM participants with abnormal LV diastolic filling had worse glycemic control as indicated by higher levels of hemoglobin A1C and fasting glucose than DM individuals with normal LV diastolic filling. Our findings complement previous observations of abnormal late diastolic LV compliance in DM. Jain et al. (32) found that greater fasting hyperglycemia in hypertensive patients correlated with increased myocardial stiffness. Experimental evidence in dogs with alloxan-induced DM suggests that myocardial glycoprotein deposition can impair the LV end-diastolic pressure/volume ratio in the absence of hypertension (35). Of note, higher plasma insulin level was not found to be associated with apparent abnormal LV relaxation, extending previous evidence that diastolic stiffness was not related to plasma insulin (36).
Potential pathogenesis.
The observation that indices of poor glycemic control were associated with abnormal LV diastolic filling in the DM population suggests that hyperglycemia may contribute to the pathogenetic mechanism of abnormal ventricular relaxation in DM. Interstitial accumulation of advanced-glycated end products (AGES), which include collagen, elastin and other connective tissue proteins, as well as fibrosis in the myocardium have been reported in human diabetic hearts (37,38), which can increase end-diastolic stiffness as well as LV mass. Quantitation of fibrosis in hypertensive, diabetic and hypertensive-diabetic hearts has revealed the lowest proportions in hypertensive hearts and the highest in hypertensive-diabetic hearts, with diabetic hearts in the midrange (37). Greater myocardial fibrosis and AGES in diabetic hearts than in hypertensive hearts parallel but, because of their greater effect on late diastolic than on early diastolic filling parameters, do not directly explain the similar abnormal relaxation seen in the DM-alone and HTN-alone groups. In addition, abnormal relaxation in subjects with DM was also associated in our study with renal microvascular disease and a trend toward arterial stiffening, which supports a systemic process in which parallel nonenzymatic production of AGES may occur in myocardium, arterioles and capacitance arteries in diabetics. Our study also showed that longer duration of DM is positively related to abnormal LV relaxation.
Another factor linking DM and abnormal LV relaxation may be the presence of coronary artery disease. Although that may be the etiology in some cases, the majority of our subjects had normal wall motion with ejection fraction 55%. In addition, when the analyses were repeated, excluding those with a history of coronary artery disease, the results remained unchanged. This finding is supported by similar reports of impaired early diastolic LV filling in asymptomatic children with DM without confounding coronary disease, obesity or hypertension (31).
Clinical implications.
This study confirms and substantially extends previous findings by revealing additional cardiovascular abnormalities associated with DM. Diabetes mellitus is associated with abnormal LV relaxation, similar to the well-known impaired relaxation associated with HTN. Abnormal LV relaxation seen in DM, independent of other factors, may contribute to the incidence of congestive heart failure despite normal LV ejection fraction, thereby being another cause of clinical cardiovascular morbidity. In addition, reduced mitral E/A ratio is independently associated with increased all-cause mortality as well as cardiovascular mortality (39). Abnormal LV filling pattern may be an early functional alteration of the left ventricle preceding systolic dysfunction. Furthermore, the association of worse glycemic control and abnormal LV filling pattern suggests that degree of hyperglycemia may play a role in the pathogenesis of diastolic dysfunction in DM. A prospective trial is needed to determine whether better glycemic control will improve LV structure and function in adults with type II DM.
Study limitations.
Doppler measurements of mitral inflow were made at the mitral annulus instead of the mitral tip, which is recommended by most consensus statements. However, the same methodology was used in all groups, and we have previously reported strong correlation between LV inflow measurement at the levels of the annulus and leaflet tips (40). Because of lack of recordings of pulmonary vein flow or mitral inflow responses to preload reduction, precluded by the need to limit echocardiogram performance time to 30 min or less, the "pseudonormalized" pattern cannot be differentiated from the true "normal" group. However, given that the population had relatively normal LV mass and normal systolic function, it is unlikely that many of our patients were pseudonormalized. The cross-sectional nature of the study limits its ability to establish causality and, thus, mechanism of the cardiovascular abnormalities associated with DM. A prospective intervention study is needed to determine the reversibility and effectiveness of treatment (i.e., glycemic and/or blood pressure control), as well as elucidating the mechanism of the adverse cardiovascular features associated with DM. The study was performed in the American Indian population, and whether the results can be generalized to other ethnic groups requires further study.
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Conclusions
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Diabetes mellitus is independently associated with abnormal LV relaxation pattern of Doppler transmitral flow velocity profiles, similar in degree to the well-known impaired relaxation associated with HTN. Abnormal LV relaxation is most severe in participants with both HTN and DM. Abnormal relaxation in individuals with DM is associated with worse glycemic control.
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Acknowledgments
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We thank the Indian Health Service, SHS participants and participating tribal communities for their extraordinary cooperation and involvement that made this study possible; Betty Jarvis, RN, Tauqeer Ali, MD, and Alan Crawford for their coordination of the three study centers; Dawn Fishman, BA, for her data coordination and management of the database; Tauqeer Ali, MD, Helen Beatty, RDMS, Joanne Carter, RDMS, Michael Cyl, RDMS, and Neil Sikes, RDMS, for their technical assistance and Virginia M. Burns for her assistance in preparation of this manuscript.
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Footnotes
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Supported in part by grants U01-HL41642, U01-HL41652 and U01-HL41654 from the National Heart, Lung and Blood Institute, Bethesda, Maryland, and M10RR0047-34 (GCRC) from the National Institutes of Health, Bethesda, Maryland. The views expressed in this paper are those of the authors and do not necessarily reflect those of the Indian Health Service.
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M. Klapholz
{beta}-Blocker Use for the Stages of Heart Failure
Mayo Clin. Proc.,
August 1, 2009;
84(8):
718 - 729.
[Abstract]
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A. Stefanidis, S. Bousboulas, J. Kalafatis, K. Baroutsi, P. Margos, K. Komninos, S. Pappas, and E. Papasteriadis
Left ventricular anatomical and functional changes with ageing in type 2 diabetic adults
Eur Heart J Cardiovasc Imaging,
July 1, 2009;
10(5):
647 - 653.
[Abstract]
[Full Text]
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R. Mogelvang, P. Sogaard, S. A. Pedersen, N. T. Olsen, P. Schnohr, and J. S. Jensen
Tissue Doppler echocardiography in persons with hypertension, diabetes, or ischaemic heart disease: the Copenhagen City Heart Study
Eur. Heart J.,
March 2, 2009;
30(6):
731 - 739.
[Abstract]
[Full Text]
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A. A. Alsaddique, A. G. Royse, C. F. Royse, and M. A. Fouda
Management of diastolic heart failure following cardiac surgery
Eur J Cardiothorac Surg,
February 1, 2009;
35(2):
241 - 249.
[Abstract]
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C. Jarnert, L. Landstedt-Hallin, K. Malmberg, A. Melcher, J. Ohrvik, H. Persson, and L. Ryden
A randomized trial of the impact of strict glycaemic control on myocardial diastolic function and perfusion reserve: a report from the DADD (Diabetes mellitus And Diastolic Dysfunction) study
Eur J Heart Fail,
January 1, 2009;
11(1):
39 - 47.
[Abstract]
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J. S. Rossi, J. D. Flaherty, G. C. Fonarow, E. Nunez, W. Gattis Stough, W. T. Abraham, N. M. Albert, B. H. Greenberg, C. M. O'Connor, C. W. Yancy, et al.
Influence of coronary artery disease and coronary revascularization status on outcomes in patients with acute heart failure syndromes: A report from OPTIMIZE-HF (Organized Program to Initiate Lifesaving Treatment in Hospitalized Patients with Heart Failure)
Eur J Heart Fail,
December 1, 2008;
10(12):
1215 - 1223.
[Abstract]
[Full Text]
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A. A. Alsaddique
Recognition of diastolic heart failure in the postoperative heart
Eur J Cardiothorac Surg,
December 1, 2008;
34(6):
1141 - 1148.
[Abstract]
[Full Text]
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H. Von Bibra, M. Diamant, P. G Scheffer, T. Siegmund, and P.-M. Schumm-Draeger
Rosiglitazone, but not glimepiride, improves myocardial diastolic function in association with reduction in oxidative stress in type 2 diabetic patients without overt heart disease
Diabetes and Vascular Disease Research,
November 1, 2008;
5(4):
310 - 318.
[Abstract]
[PDF]
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K. Steine, J. R. Larsen, M. Stugaard, T. J. Berg, M. Brekke, and K. Dahl-Jorgensen
LV systolic impairment in patients with asymptomatic coronary heart disease and type 1 diabetes is related to coronary atherosclerosis, glycaemic control and advanced glycation endproducts
Eur J Heart Fail,
October 1, 2007;
9(10):
1044 - 1050.
[Abstract]
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S. Boudina and E. D. Abel
Diabetic Cardiomyopathy Revisited
Circulation,
June 26, 2007;
115(25):
3213 - 3223.
[Abstract]
[Full Text]
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R. Wachter, C. Luers, S. Kleta, K. Griebel, C. Herrmann-Lingen, L. Binder, N. Janicke, D. Wetzel, M. M. Kochen, and B. Pieske
Impact of diabetes on left ventricular diastolic function in patients with arterial hypertension
Eur J Heart Fail,
May 1, 2007;
9(5):
469 - 476.
[Abstract]
[Full Text]
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L. d. l. Fuentes, A. L. Brown, S. J. Mathews, A. D. Waggoner, P. F. Soto, R. J. Gropler, and V. G. Davila-Roman
Metabolic syndrome is associated with abnormal left ventricular diastolic function independent of left ventricular mass
Eur. Heart J.,
March 1, 2007;
28(5):
553 - 559.
[Abstract]
[Full Text]
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M. Galderisi
Diastolic Dysfunction and Diabetic Cardiomyopathy: Evaluation by Doppler Echocardiography
J. Am. Coll. Cardiol.,
October 17, 2006;
48(8):
1548 - 1551.
[Abstract]
[Full Text]
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H. Matsui, T. Shimosawa, Y. Uetake, H. Wang, S. Ogura, T. Kaneko, J. Liu, K. Ando, and T. Fujita
Protective Effect of Potassium Against the Hypertensive Cardiac Dysfunction: Association With Reactive Oxygen Species Reduction
Hypertension,
August 1, 2006;
48(2):
225 - 231.
[Abstract]
[Full Text]
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H. Von Bibra, I. S Thrainsdottir, A. Hansen, V. Dounis, K. Malmberg, and L. Ryden
Tissue Doppler imaging for the detection and quantitation of myocardial dysfunction in patients with type 2 diabetes mellitus
Diabetes and Vascular Disease Research,
February 1, 2005;
2(1):
24 - 30.
[Abstract]
[PDF]
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P. M. Okin, R. B. Devereux, E. T. Lee, J. M. Galloway, and B. V. Howard
Electrocardiographic Repolarization Complexity and Abnormality Predict All-Cause and Cardiovascular Mortality in Diabetes: The Strong Heart Study
Diabetes,
February 1, 2004;
53(2):
434 - 440.
[Abstract]
[Full Text]
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N. H. Andersen, S. H. Poulsen, K. Helleberg, P. Ivarsen, S. T. Knudsen, and C. E. Mogensen
Impact of Essential Hypertension and Diabetes Mellitus on Left Ventricular Systolic and Diastolic Performance
Eur Heart J Cardiovasc Imaging,
December 1, 2003;
4(4):
306 - 312.
[Abstract]
[Full Text]
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V. Palmieri, R. P. Tracy, M. J. Roman, J. E. Liu, L. G. Best, J. N. Bella, D. C. Robbins, B. V. Howard, and R. B. Devereux
Relation of Left Ventricular Hypertrophy to Inflammation and Albuminuria in Adults With Type 2 Diabetes: The Strong Heart Study
Diabetes Care,
October 1, 2003;
26(10):
2764 - 2769.
[Abstract]
[Full Text]
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T. P. Didangelos, G. A. Arsos, D. T. Karamitsos, V. G. Athyros, and N. D. Karatzas
Left Ventricular Systolic and Diastolic Function in Normotensive Type 1 Diabetic Patients With or Without Autonomic Neuropathy: A radionuclide ventriculography study
Diabetes Care,
July 1, 2003;
26(7):
1955 - 1960.
[Abstract]
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S. D. Solomon, M. S. J. Sutton, G. A. Lamas, T. Plappert, J. L. Rouleau, H. Skali, L. Moye, E. Braunwald, M. A. Pfeffer, and for the Survival And Ventricular Enlargement (SAVE
Ventricular Remodeling Does Not Accompany the Development of Heart Failure in Diabetic Patients After Myocardial Infarction
Circulation,
September 3, 2002;
106(10):
1251 - 1255.
[Abstract]
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Abstract
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