Association of albuminuria with systolic and diastolic left ventricular dysfunction in type 2 diabetes: the Strong Heart Study

OBJECTIVES: We sought to compare systolic and diastolic function in American Indians with diabetes mellitus (DM) based on albuminuria status. BACKGROUND: Albuminuria has been shown to predict cardiovascular disease (CVD) in populations with DM. However, the mechanism of the association of albuminuria and CVD is unclear. METHODS: We compared echo-derived indices of left ventricular (LV) systolic and diastolic function in three groups of American Indians with DM based on albuminuria status: I = no albuminuria (<30 mg albumin/g creatinine); II = microalbuminuria (30 to 300 mg/g); and III = macroalbuminuria (>300 mg/g). RESULTS: Group II and III were slightly older than Group I with no significant gender difference between groups. Systolic blood pressure increased and body mass index decreased from Group I to Group III. Left ventricular systolic function was lower in the groups with albuminuria with step-wise decreases in ejection fraction and stress-corrected midwall shortening (MWS) from Group I to Group III. Similar findings were noted in diastolic LV filling with lower mitral E/A ratios and longer deceleration times in groups with albuminuria. The proportion of participants with abnormal MWS and abnormal LV diastolic relaxation showed step-wise increases from no albuminuria to macroalbuminuria. In multivariate analysis, albuminuria status remained independently associated with both systolic and diastolic dysfunction after adjusting for age, gender, body mass index, systolic blood pressure, duration of diabetes, coronary artery disease, and LV mass. CONCLUSIONS: Albuminuria is independently associated with LV systolic and diastolic dysfunction in type 2 DM; this may explain in part the relationship of albuminuria to increased cardiovascular (CV) events in the DM population. Screening for albuminuria identifies individuals with high CV risk and possible cardiac dysfunction.     

Prevalence of diastolic dysfunction in normotensive, asymptomatic patients with well-controlled type 2 diabetes mellitus

To evaluate the prevalence of left ventricular (LV) diastolic dysfunction in patients with type 2 diabetes mellitus free of cardiovascular disease, we studied 86 normotensive men and women (mean age 46 +/- 6 years) with Doppler echocardiography. All subjects were asymptomatic for ischemic heart disease or heart failure. The traditional transmitral filling patterns were used to characterize diastolic physiology. The Valsalva maneuver was used to differentiate normal from pseudonormal LV filling pattern. All patients had a normal electrocardiogram at rest and a negative result on exercise echocardiography for inducible wall motion abnormalities. Global LV systolic function was normal (mean LV ejection fraction 58%, range 53% to 76%). Diastolic dysfunction was found in 41 subjects (47%) of which 26 (30%) had impaired relaxation and 15 (17%) had a pseudonormal filling pattern. The mean LV mass index was 101 g/m2 (range 86 to 122). All patients with a normal-filling physiology had gender-adjusted normal LV mass index (mean 93 +/- 11 g/m2), whereas 62% of those with either abnormal relaxation (mean 103 +/- 12 g/m2, p <0.001) or a pseudonormal pattern (mean 110 +/- 12 g/m2, p <0.001) had increased LV mass index. No subject in this cohort had restrictive diastolic physiology. In conclusion, diastolic dysfunction in type 2 diabetes mellitus patients is often found despite adequate metabolic control and freedom from clinically detectable heart disease. The Valsalva maneuver can unmask an additional 17% of patients with subclinical abnormal LV filling pattern, who otherwise would be classified as having a normal diastolic physiology. Increased LV mass index is closely associated with abnormal LV filling characteristics.     

Prevalence of left ventricular diastolic dysfunction in obese persons with and without diabetes mellitus

Forty obese diabetic patients (mean age 48 +/- 9 years) and 93 obese nondiabetic patients (mean age 43 +/- 9 years) underwent Doppler and tissue Doppler echocardiographic evaluation of left ventricular diastolic function before gastric bypass surgery. Moderate or severe left ventricular diastolic dysfunction was present in 24 of 40 obese diabetics (60%) and in 21 of 93 obese nondiabetics (23%) (p <0.001).     

Prevalence and prognosis of asymptomatic left ventricular diastolic dysfunction in ambulatory patients with coronary heart disease

The association of asymptomatic left ventricular (LV) diastolic dysfunction with cardiovascular outcomes in ambulatory patients with coronary heart disease (CHD) and no history of heart failure (HF) was examined. LV diastolic HF predicts adverse cardiovascular outcomes. However, the prevalence and prognosis of asymptomatic LV diastolic dysfunction in patients with established CHD in the absence of clinical HF is unknown. Six hundred ninety-three patients with stable CHD, normal systolic function (LV ejection fraction>or=50%), and no history of HF were evaluated. Echocardiography was used to classify LV diastolic function, and Cox proportional hazards models were used to evaluate the association of LV diastolic dysfunction with cardiovascular outcomes during 3 years of follow-up. Of 693 subjects with normal systolic function and no history of HF, 455 (66%) had normal LV diastolic function, 166 (24%) had mild LV diastolic dysfunction, and 72 (10%) had moderate to severe LV diastolic dysfunction. After multivariable adjustment, the presence of moderate to severe LV diastolic dysfunction was strongly predictive of incident hospitalization for HF (hazard ratio 6.3, 95% confidence interval 2.4 to 16.1, p=0.0003) and death from heart disease (HR 3.9, 95% confidence interval 1.0 to 14.8, p=0.05). In conclusion, moderate to severe LV diastolic dysfunction was present in 10% of patients with stable CHD with normal ejection fraction and no history of HF and predicts subsequent hospitalization for HF and death from heart disease. Patients with asymptomatic LV diastolic dysfunction may benefit from more aggressive therapy to prevent or delay the development of HF.     

Effects of exercise training on diastolic and systolic dysfunction in patients with chronic heart failure

BACKGROUNDChronic heart failure (CHF) is a complex syndrome characterized by a progressive reduction of the left ventricular (LV) contractility, low exercise tolerance, and increased mortality and morbidity. Diastolic dysfunction (DD) of the LV, is a keystone in the pathophysiology of CHF and plays a major role in the progression of most cardiac diseases. Also, it is well estimated that exercise training induces several beneficial effects on patients with CHF. AIMTo evaluate the impact of a cardiac rehabilitation program on the DD and LV ejection fraction (EF) in patients with CHF.METHODSThirty-two stable patients with CHF (age: 56 ± 10 years, EF: 32% ± 8%, 88% men) participated in an exercise rehabilitation program. They were randomly assigned to aerobic exercise (AER) or combined aerobic and strength training (COM), based on age and peak oxygen uptake, as stratified randomization criteria. Before and after the program, they underwent a symptom-limited maximal cardiopulmonary exercise testing (CPET) and serial echocardiography evaluation to evaluate peak oxygen uptake (VO_2peak), peak workload (W_peak), DD grade, right ventricular systolic pressure (RVSP), and EF.RESULTSThe whole cohort improved VO_2peak, and W_peak, as well as DD grade (P < 0.05). Overall, 9 patients (28.1%) improved DD grade, while 23 (71.9%) remained at the same DD grade; this was a significant difference, considering DD grade at baseline (P < 0.05). In addition, the whole cohort improved RVSP and EF (P < 0.05). Not any between-group differences were observed in the variables assessed (P > 0.05).CONCLUSIONExercise rehabilitation improves indices of diastolic and systolic dysfunction. Exercise protocol was not observed to affect outcomes. These results need to be further investigated in larger samples.     

Prevalence of ventricular diastolic dysfunction in asymptomatic, normotensive patients with diabetes mellitus

To determine the prevalence of left ventricular diastolic dysfunction in asymptomatic, normotensive patients with type 2 diabetes mellitus, we studied 61 consecutive normotensive patients with type 2 diabetes using conventional Doppler echocardiography at rest (deceleration time, isovolumic relaxation time, early diastolic velocity [E]/peak atrial systolic velocity [A] ratio), and during the Valsalva maneuver. In addition, mitral annular velocity and velocity of flow propagation were assessed in all patients using tissue Doppler imaging (TDI) and color M-mode echocardiography. A standard resting echocardiogram excluded significant valvular disease and stress echocardiography excluded significant coronary artery disease in those with diastolic dysfunction. Diastolic dysfunction was found in 43 of 57 patients (75%) when all of the above echocardiographic techniques were used. TDI detected diastolic dysfunction more often (63%) than any other echocardiographic approach. Thus, the prevalence of left ventricular diastolic dysfunction in asymptomatic, normotensive patients with type 2 diabetes without significant coronary artery disease is much higher than previously suspected. TDI markedly improved the echocardiographic detection of diastolic dysfunction in asymptomatic patients with type 2 diabetes.     

Endothelial dysfunction associated with left ventricular diastolic dysfunction in patients with coronary heart disease

OBJECTIVE: We sought to assess the correlation between endothelial vasodilation and left ventricular diastolic function. BACKGROUND: Previous studies have demonstrated that similar neurohumoral factors are involved in myocardial and vascular endothelial impairment. The degree of endothelial dysfunction is related to the clinical severity of the heart failure. However, it is not clear whether endothelial dysfunction develops with the progression of left ventricular diastolic dysfunction. We hypothesize that the endothelial dysfunction is associated with left ventricular diastolic dysfunction. METHODS: Using high-resolution ultrasound, we measured the dilator response of the brachial artery to hyperemia (endothelium-dependent vasodilation) and to 0.5 mg nitroglycerin (endothelium-independent vasodilation), and measured peak velocities of the early wave (Evmax) and the atrial wave (Avmax) in 40 coronary heart disease (CHD) patients and 20 normal subjects. We analyzed the relationship between the Evmax/Avmax ratio and endothelium-dependent vasodilation. RESULTS: The results showed that endothelium-dependent and endothelium-independent vasodilation as well as the Evmax/Avmax ratio were lower in the CHD group than those in the control group (4.29%+/-1.42%, 17.58%+/-2.99%, 0.81+/-0.24 vs. 9.62%+/-2.34%, 24.18%+/-3.15%, 1.07+/-0.29, respectively, P<0.01). The Evmax/Avmax ratio was related to endothelium-dependent vasodilation (r=0.45, P<0.01). CONCLUSIONS: Our results showed that the development of endothelial dysfunction was associated with the progression of myocardial diastolic dysfunction, which suggests that the same mechanisms may be involved in the impairment of endothelium and myocardium.     

Sympathetic dysfunction in type 1 diabetes: association with impaired myocardial blood flow reserve and diastolic dysfunction

OBJECTIVES: This study was designed to explore the relationships of early diabetic microangiopathy to alterations of cardiac sympathetic tone and myocardial blood flow (MBF) regulation in subjects with stable type 1 diabetes. BACKGROUND: In diabetes, augmented cardiac sympathetic tone and abnormal MBF regulation may predispose to myocardial injury and enhanced cardiac risk. METHODS: Subject groups comprised healthy controls (C) (n = 10), healthy diabetic subjects (DC) (n = 12), and diabetic subjects with very early diabetic microangiopathy (DMA+) (n = 16). [(11)C]meta-hydroxyephedrine ([(11)C]HED) and positron emission tomography (PET) were used to explore left ventricular (LV) sympathetic integrity and [(13)N]ammonia-PET to assess MBF regulation in response to cold pressor testing (CPT) and adenosine infusion. RESULTS: Deficits of LV [(11)C]HED retention were extensive and global in the DMA+ subjects (36 +/- 31% vs. 1 +/- 1% in DC subjects; p < 0.01) despite preserved autonomic reflex tests. On CPT, plasma norepinephrine excursions were two-fold greater than in C and DC subjects (p < 0.05), and basal LV blood flow decreased (-12%, p < 0.05) in DMA+ but not in C or DC subjects (+45% and +51%, respectively). On adenosine infusion, compared with C subjects, MBF reserve decreased by approximately 45% (p < 0.05) in DMA+ subjects. Diastolic dysfunction was detected by two-dimensional echocardiography in 5 of 8 and 0 of 8 consecutively tested DMA+ and DC subjects, respectively. CONCLUSIONS: Augmented cardiac sympathetic tone and responsiveness and impaired myocardial perfusion may contribute to myocardial injury in diabetes.     

Combined circumferential and longitudinal left ventricular systolic dysfunction in patients with type 2 diabetes mellitus without myocardial ischemia

BACKGROUND/OBJECTIVE:

Left ventricular (LV) circumferential or longitudinal shortening may be impaired in patients with type 2 diabetes mellitus (DM). In the present study, patients with type 2 DM without myocardial ischemia and combined impairment of circumferential and longitudinal (C+L) shortening were studied to assess the prevalence and factors associated with this condition.

METHODS:

Data from 386 patients with type 2 DM enrolled in the SHORTening of midWall and longitudinAl left Ventricular fibers in diabEtes study were analyzed. One hundred twenty healthy subjects were used to define C+L dysfunction. Stress-corrected midwall shortening and mitral annular peak systolic velocity were considered as indexes of C+L shortening and classified as low if <89% and <8.5 cm/s, respectively (10th percentiles of controls).

RESULTS:

Combined C+L dysfunction was detected in 66 patients (17%). The variables associated with this condition were lower glomerular filtration rate (OR 0.98 [95% CI 0.96 to 0.99], greater LV mass (OR 1.05 [95% CI 1.02 to 1.08]), high pulmonary artery wedge pressure (OR 1.23 [95% CI 1.04 to 1.44]) and mitral annular calcifications (OR 3.35 [95% CI 1.71 to 6.55]). Considering the entire population, the relationship between stress-corrected midwall shortening and peak systolic velocity was poor (r=0.20), and the model was linear. The relationship was considerably closer and nonlinear in patients with combined C+L dysfunction (r=0.61; P<0.001), having the best fit by cubic function.

CONCLUSIONS:

Combined C+L dysfunction was present in one-sixth of patients with type 2 DM without myocardial ischemia. This condition was associated with reduced renal function, worse hemodynamic status and structural LV abnormalities, and may be considered a preclinical risk factor for heart failure.     

Heart rate variability and diastolic dysfunction in patients with type 2 diabetes mellitus

Cardiovascular autonomic neuropathy is a common form of autonomic dysfunction in diabetes mellitus (DM) and associates abnormalities in heart rate control and in vascular dynamics. This study evaluates the impact of diabetes mellitus on left ventricular diastolic dysfunction (LVDD) and heart rate variability in a group of type 2 diabetes mellitus without signs of cardiovascular disease. The study group consisted of 58 patients, aged 61 ± 8 years, diagnosed with type 2 DM. The subjects were selected from a series of 104 consecutive diabetic patients. All the subjects were on oral therapy or on diet for DM, and ECG was normal for all the subjects. The control group consisted of 45 healthy subjects, matched for age and sex. Heart rate variability was measured using a 24-h ECG monitoring system, and standard 2D and Doppler echocardiography was performed in all the subjects. There are significant differences between groups regarding disease duration, longer in patients with impaired relaxation (11.22 ± 9.17 vs. 8.31 ± 8.95 years), and disease control, worse in impaired relaxation group. Heart rate in impaired relaxation group is significantly higher than in controls, and higher, but not significantly, when compared with normal group (91 ± 10, vs. 88 ± 11 and 71 ± 11, respectively). Cardiac autonomic neuropathy was associated with LVDD in patients with type 2 DM, but without clinically manifest heart disease. Twenty-four-hour ECG monitoring and echocardiography can detect diabetic cardiomyopathy in early stages and should be performed in all subjects.     

No evidence for systolic or diastolic left ventricular dysfunction at rest in selected patients with long-term type I diabetes mellitus

We assessed left ventricular systolic and diastolic function using pulsed-waved Doppler echocardiography in a selected group of 20 patients with insulin-dependent diabetes mellitus (IDDM) (mean age, 35 +/- 8 years; mean diabetes duration, 17 + 7 years). Our patients were free of autonomic neuropathy and major micro- or macrovascular complications and had no evidence of ischemic heart disease or hypertension. The results were compared with those of 20 age- and sex-matched control subjects. We found that left ventricular geometry and mass, systolic function by M-mode and 2D-echocardiography, isovolumetric relaxation time, deceleration time and the PEP/LVET ratio were not significantly different between patients and control subjects. Hemodynamic parameters were also not significantly different except for a slightly higher heart rate in the patient group (75 +/- 11 vs. 68 + 6 bpm, P = 0.019). After correction of A-peak velocities for differences in heart rate, there was no significant difference of Doppler indices of diastolic left ventricular function between patients and control subjects. The absence of significant left ventricular systolic and diastolic dysfunction by Doppler echocardiography in our study patients may be explained by our patient selection. Left ventricular dysfunction in diabetic patients without concomitant hypertensive or ischemic heart disease may only occur in conjunction with microvascular disease in other organ systems, with autonomic neuropathy or with poor metabolic control.     

Relation of serum heart type fatty acid binding protein to left ventricular diastolic dysfunction in patients with type 2 diabetes and early diabetic kidney disease

AimsWe aimed to investigate the serum level of heart type fatty acid binding protein (H-FABP) and its relation to left ventricular (LV) diastolic dysfunction in patients with type 2 diabetes (T2DM) and early diabetic kidney disease (DKD).MethodsThis study was conducted on 100 T2DM patients divided into 50 patients with early DKD and 50 patients without DKD. Doppler echocardiography was used to assess LV function and serum H-FABP levels were measured using ELISA technique.Results78% of patients with DKD and 12% of patients without DKD had LV diastolic dysfunction. Among patients with DKD, those with diastolic dysfunction had significantly higher urinary albumin to creatinine ratio (UACR) (p = 0.041). H-FABP levels were significantly higher in patients with DKD (p?0.001) and it had significant positive correlation with UACR (p = 0.009). No significant difference was found regarding serum H-FABP levels between patients with normal LV function and those with diastolic dysfunction in both study groups.ConclusionDiastolic dysfunction is a common finding among patients with T2DM. UACR, but not serum H-FABP, is significantly associated with diastolic dysfunction in patients with early DKD. Serum H-FABP level is significantly higher in early DKD and positively correlated with the level of albuminuria.     

Poor glycemic control predicts coronary heart disease events in patients with type 1 diabetes without nephropathy

Patients with type 1 diabetes mellitus, especially those with nephropathy, are at increased risk for coronary heart disease (CHD). However, information on the predictive value of cardiovascular risk factors and the degree of hyperglycemia with respect to CHD events in patients with type 1 diabetes without nephropathy is still incomplete. Therefore, we performed a prospective study on risk factors for CHD in patients with type 1 diabetes free of clinical nephropathy. At baseline examination, cardiovascular risk factor levels of CHD were determined in 177 patients with type 1 diabetes (87 men and 90 women), age 45 to 64 years at baseline and >/=30 years at the time of diagnosis of diabetes. These patients were followed up to 7 years with respect to CHD events. Altogether, 20 patients with type 1 diabetes (13 men [7.3%] and 7 women [3.9%]) died of CHD and 28 patients with type 1 diabetes (17 men [9.6%] and 11 women [6.2%]) had a serious CHD event (death from CHD or nonfatal myocardial infarction). In multivariate Cox regression analysis, a previous history of myocardial infarction (hazard ratio [HR] and its 95% confidence interval, 8.0 [3.1 to 21.0], P<0.001), high glycohemoglobin A1 (>10.4%, the highest tertile, HR 5.4 [1.4 to 20.4], P=0.013), and the duration of diabetes (>16 years, the highest tertile, HR 4.2 [1.3 to 12.9], P=0.013) were the only variables associated with CHD death even after adjustment for other cardiovascular risk factors. These variables also predicted the incidence of all CHD events. Our results indicate that poor metabolic control is a strong predictor of CHD events in patients with late-onset type 1 diabetes without nephropathy, independently of other cardiovascular risk factors.     

Three-dimensional assessment of left ventricular systolic strain in patients with type 2 diabetes mellitus, diastolic dysfunction, and normal ejection fraction

Left ventricular (LV) diastolic dysfunction often occurs in patients with type 2 diabetes mellitus (DM) independent of atherosclerotic coronary artery disease, myocardial ischemia, and regional wall motion anomalies. Limited information exists on LV myocardial tissue strain in this patient group. We measured 3-dimensional (3-D) parameters of LV systolic and diastolic functions in 28 patients who had type 2 DM (age 33 to 70 years), standard echocardiographic evidence of LV diastolic dysfunction, and normal LV ejection fraction, and 31 normal control subjects (age 19 to 74 years) who had no evidence of cardiac disease, with multislice cine anatomic and tagged magnetic resonance imaging. Three-dimensional analysis of the resulting images showed that peak systolic mitral valve plane displacement was 12% smaller (p = 0.040) and peak diastolic mitral valve plane velocity was 21% lower (p = 0.008) in patients who had DM than in normal controls. Peak systolic circumferential and longitudinal strains and principal 3-D shortening strain were 14%, 22%, and 10% smaller, respectively, in the DM group (p <0.001 for each). Peak diastolic rate of relaxation of circumferential and longitudinal strains and principal 3-D shortening strain were 35%, 32%, and 33% lower, respectively, in the DM group (p <0.001 for each). Thus, LV systolic circumferential, longitudinal and 3-D principal strains, and diastolic strain rates are impaired in patients who have type 2 DM, LV diastolic dysfunction, and normal LV ejection fraction.     

Congestive heart failure in patients with normal left ventricular systolic function: a manifestation of diastolic dysfunction.

Diastolic dysfunction is a relatively common problem that may be mild and asymptomatic or may present with congestive heart failure and severe disabling symptoms. It is frequently due to coronary artery disease or left ventricular hypertrophy and it is especially common in the older population. The pathophysiology is related to increased left ventricular passive stiffness and impaired or slowed myocardial relaxation. Patients with diastolic dysfunction are best treated with calcium channel blocking agents or beta-blocking agents (drugs that are generally avoided in patients with significant systolic dysfunction). Most treatment is based on symptomatic relief, and therefore periods of cautious trial and error are the rule. Congestive symptoms are treated with agents that reduce pulmonary venous pressure; in general positive inotropic agents and arterial vasodilators are not useful in heart failure that is due to diastolic dysfunction.