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PubMedDate not supplied

Advanced glycation end product cross-linking: pathophysiologic role and therapeutic target in cardiovascular disease.

Advanced glycation end products (AGEs) form by a nonenzymatic reaction between reducing sugars and biological proteins. These stable compounds accumulate slowly throughout the life span and contribute to structural and physiologic changes in the cardiovascular system such as increased vascular and myocardial stiffness, endothelial dysfunction, altered vascular injury responses, and atherosclerotic plaque formation. Mechanisms underlying these alterations include AGE cross-linking of collagen and AGE interactions with circulating proteins and AGE receptors. The clinical manifestations of AGE accrual-isolated systolic hypertension, endothelial and diastolic dysfunction, and atherosclerosis-underscore their role in increased cardiovascular risk associated with aging as well as diabetes and hypertension, conditions that enhance AGE formation. New pharmacologic agents that prevent AGE, break cross-links, or block AGE receptors reduce vascular and myocardial stiffness, inhibit atherosclerotic plaque formation, and improve endothelial function. These agents promise to reduce the risk of isolated systolic hypertension, diastolic dysfunction, and diabetes, and thus, heart failure.

Animals↗
PubMed2006

Amount of left ventricular hypertrophy determines the plasma N-terminal pro-brain natriuretic peptide level in patients with hypertrophic cardiomyopathy and normal left ventricular ejection fraction.

BACKGROUND: N-terminal pro-brain natriuretic peptide (NT-proBNP) is increased in patients with hypertrophic cardiomyopathy (HCM); however, the determinants of NT-proBNP level have not been clarified in HCM. HYPOTHESIS: This study was performed to determine the relationship between NT-proBNP levels and various echocardiographic variables of patients with HCM and normal left ventricular ejection fraction (LVEF). METHODS: We assessed plasma NT-proBNP levels and echocardiographic variables of 36 patients (19 men, 58 +/- 14 years) with HCM and an LVEF of > or = 55%. Echocardiographic variables measured were LV wall thickness, end-diastolic LV internal dimension (LVIDd) and volume (LVEDV), LV mass, and LV mass index (LV mass/body surface area, LVMI). Left ventricular outflow tract pressure gradient, transmitral E and A velocities, deceleration time (DT) of the transmitral E wave, and septal annular E' velocity were measured by Doppler technique. The relationship between echocardiographic variables and plasma NT-proBNP level was analyzed. RESULTS: The plasma NT-proBNP level was 775.2 +/- 994.2 pg/ml (range 33.1-4729.0 pg/ml). It showed positive correlations with LV end-diastolic septal thickness (r = 0.39, p = 0.010) and LVMI (r = 0.27, p = 0.050), while it revealed negative correlations with LVIDd (r = -0.44, p = 0.004), LVEDV (r = -0.44, p = 0.004) and DT(r = -0.31,p = 0.034). The NT-proBNP level was higher in the patients with than in those without LV diastolic dysfunction (p = 0.033) and was independently related to LVIDd (p = 0.001), LVMI (p = 0.006) and DT (p = 0.031) by multivariate analysis. CONCLUSION: In patients with HCM and normal LVEF, the amount of LV hypertrophy and LV diastolic dysfunction may exert a significant role in determining plasma NT-proBNP level.

Adult↗
PubMed2004

Uncovering a hidden epidemic: a study of the current burden of heart failure in Australia.

BACKGROUND: Australia, like other countries, is experiencing an epidemic of heart failure (HF). However, given the lack of national and population-based datasets collating detailed cardiovascular-specific morbidity and mortality outcomes, quantifying the specific burden imposed by HF has been difficult. METHODS: Australian Bureau of Statistics (ABS data) for the year 2000 were used in combination with contemporary, well-validated population-based epidemiologic data to estimate the number of individuals with symptomatic and asymptomatic HF related to both preserved (diastolic dysfunction) and impaired left ventricular systolic (dys)function (LVSD) and rates of HF-related hospitalisation. RESULTS: In 2000, we estimate that around 325,000 Australians (58% male) had symptomatic HF associated with both LVSD and diastolic dysfunction and an additional 214,000 with asymptomatic LVSD. 140,000 (26%) live in rural and remote regions, distal to specialist health care services. There was an estimated 22,000 incidents of admissions for congestive heart failure and approximately 100,000 admissions associated with this syndrome overall. CONCLUSION: Australia is in the midst of a HF epidemic that continues to grow. Overall, it probably contributes to over 1.4 million days of hospitalization at a cost of more than 1 billion dollars. A national response to further quantify and address this enormous health problem is required.

Journal Article↗
PubMed1998

Objectives of high blood pressure treatment: left ventricular hypertrophy, diastolic function, and coronary reserve.

The prehypertrophic state of hypertensive heart disease is characterized by morphologic changes (interstitial fibrosis, increase in intramyocardial arteriolar wall thickness) as well as by functional alterations (diastolic dysfunction, decrease in coronary reserve). These changes most probably represent the earliest cardiac end-organ lesions that can clinically be detected. In cardiac hypertrophy, long-term (9-12 months) pharmacotherapy with beta-blockers, calcium channel blockers, or ACE inhibitors reverses left ventricular hypertrophy by 8% to 14%, whereas marked improvement in coronary reserve and diastolic dysfunction is achieved by calcium blocker and preferably by ACE inhibitors.

Antihypertensive Agents↗
PubMed2003

Influence of low high-density lipoprotein cholesterol on left ventricular hypertrophy and diastolic function in essential hypertension.

BACKGROUND: Left ventricular (LV) hypertrophy and LV diastolic dysfunction, which are common cardiac changes in hypertensive patients, are modified by several nonhemodynamic (eg, genetic, neurohumoral, and metabolic) factors. However, the influence of serum lipids on these LV changes has not been sufficiently studied. Although low high-density lipoprotein (HDL) cholesterol is well known to be a major risk factor for coronary heart disease, it is unclear whether HDL cholesterol plays a role in hypertensive heart disease. METHODS: In 274 patients with treated essential hypertension, two-dimensional and Doppler echocardiography were performed, and LV mass, ratio of peak velocity of atrial filling to early diastolic filling (A to E ratio [A/E]), and deceleration time of the E-wave were evaluated. The relationship of dyslipidemia, especially low HDL cholesterol, to LV hypertrophy and diastolic function was investigated in these patients. RESULTS: In a univariate regression analysis, HDL cholesterol was inversely associated with LV mass, A/E, and deceleration time. The association of HDL cholesterol with LV diastolic function was observed in both men and women. Its association with LV mass was gender-dependent, being significant only in women. Triglycerides were weakly correlated with LV mass and A/E, but total and low-density lipoprotein cholesterol had no correlations with these indices. In a multiple regression analysis, only low HDL cholesterol among several lipid levels was an independent predictor of both LV mass and LV diastolic dysfunction. CONCLUSIONS: Our findings suggest that low HDL cholesterol may unfavorably modify LV structure and diastolic function in patients with treated essential hypertension.

Aged↗
PubMed1997

Effects of calcium on left ventricular function early after cardiopulmonary bypass.

OBJECTIVES: Evaluation of the effects of intravenous CaCl2 on systolic and diastolic function early after separation from cardiopulmonary bypass (CPB) DESIGN: Prospective study SETTING: University hospital PARTICIPANTS: Twenty patients scheduled for elective coronary artery surgery INTERVENTIONS: Left ventricular (LV) pressures were measured with fluid-filled catheters. Data were digitally recorded during pressure elevation induced by tilt-up of the legs. Transgastric short-axis echocardiographic views of the LV were simultaneously recorded on videotape. Measurements were obtained before the start of CPB, 10 minutes after termination of CPB, after intravenous administration of CaCl2, 5 mg/kg, and 10 minutes later. MEASUREMENTS AND MAIN RESULTS: Systolic function was evaluated with the slope (Ees, mmHg/mL) of the systolic pressure-volume relation. Diastolic function was evaluated with the chamber stiffness constant (Kc, mmHg/mL) of the diastolic pressure-volume relation. CaCl2 increased Ees from 2.62 +/- 0.46 to 5.58 +/- 0.61 (mean +/- SD), but induced diastolic dysfunction with an increase in Kc from 0.011 +/- 0.006 to 0.019 +/- 0.007. These changes were transient and had disappeared within 10 minutes after administration of CaCl2. CONCLUSIONS: CaCl2 early after CPB transiently improved systolic function at the expense of an increase in ventricular stiffness, suggesting temporary diastolic dysfunction.

Adult↗
PubMed1992

The antihypertensive and cardiac hemodynamic effects of nebivolol.

Acute, subacute, and chronic treatment with nebivolol, a novel beta 1-selective adrenergic antagonist, significantly lowered systolic and diastolic blood pressure and heart rate in patients with essential hypertension. No orthostatism and bradycardia were reported. A comparison between a normal control group and 23 hypertensive patients revealed that the ratio between the preejection period (PEP) and the left ventricular ejection time (LVET) of the systolic time intervals (STI) was significantly increased in the hypertensive patients, owing to a prolongation of the PEPc (PEP corrected for heart rate). Treatment with nebivolol 5 mg once a day significantly improved the PEP/LVET, in acute conditions from 0.42 +/- 0.023 to 0.39 +/- 0.018, after one month of treatment from 0.40 +/- 0.013 to 0.36 +/- 0.013 and after one year of treatment from 0.41 +/- 0.012 to 0.36 +/- 0.010, owing to a significant shortening of the PEPc. There was no correlation between changes of blood pressure and changes of STI. Diastolic dysfunction is an early finding in hypertension and may well be reflected in the prolongation of the PEPc. The improvement of left ventricular performance, as measured with STI, suggests that treatment with nebivolol may favorably influence the underlying diastolic dysfunction and be of therapeutic value for hypertensive patients with left ventricular damage.

Adrenergic beta-Antagonists↗
PubMed1995

[Left ventricular function in post-endocarditis aortic insufficiency and aortic-annular ectasia].

BACKGROUND: The duration of valvular regurgitation is an important determinant of left ventricular function in the presence of severe volume overload. PURPOSE: To evaluate the effect of aortic regurgitation (aortoannullar dilatation vs. history of bacterial endocarditis) on left ventricular (LV) function. PATIENTS: Between February 1976 and January 1993 45 patients (mean; age 45 +/- 12 years) underwent diagnostic evaluation for clinical purposes. Patients were divided into three groups: group 1 consisted of 17 patients with normal LV function (controls), group 2 of 11 patients with severe aortic regurgitation due to aortoannullar dilatation (AAD) and group 3 of patients with severe aortic regurgitation and a history of bacterial endocarditis (BE). METHODS: LV function was assessed by biplane LV-angiography and simultaneous pressure recordings. The ejection fraction and peak systolic wall stress were calculated in all patients. Systolic and diastolic LV function was determined and compared within the three groups. RESULTS: Heart rate, mean aortic pressure and cardiac index were similar in the three groups. The mean aortic diameter was significantly increased in group 2 when compared to the other two groups (p < 0,001). Systolic function was significantly reduced in both groups with aortic regurgitation when compared to the control patients. The end diastolic pressure-volume relationship was shifted to the right in patients with aortic regurgitation, but only 3 patients with a history of bacterial endocarditis showed severe diastolic dysfunction. CONCLUSIONS: No hemodynamic differences were observed in patients with severe aortic regurgitation with regard to the etiology or time course of LV volume overload. However, 17% of the patients with a history of bacterial endocarditis had severe diastolic dysfunction, which is probably due to the faster development of volume overload after bacterial endocarditis.

Adult↗
PubMed1995

[Congestive heart failure in the elderly. Value of Doppler echocardiography].

Fifty-eight consecutive elderly patients (seven men and 51 women, mean age 84 +/- 6) admitted for congestive heart failure were prospectively investigated by doppler echocardiography in order to 1) define the prevalence of cardiac failure with normal left ventricular systolic function, 2) estimate the role of abnormalities of left ventricular filling (diastolic dysfunction), 3) evaluate echodoppler parameters for assessment of diastolic function: ratio of early peak on atrial peak of filling velocities (E/A), mitral deceleration time (MDT) and isovolumic relaxation time (IRT). Of the 58 patients, 32 (55%) had normal left ventricular systolic function and 26 (45%) had systolic dysfunction. Of the 32 patients with normal systolic function, diastolic function could not be evaluated in nine patients, was abnormal in 16 and normal in seven. Congestive heart failure with normal systolic function is very frequent in the elderly subject. Sensitivity of clinical data being too low, doppler echocardiography is the easiest noninvasive technique for defining abnormalities of both left ventricular systolic and diastolic function. In the elderly, MDT and IRT are more sensitive parameters than E/A for the diagnosis of diastolic dysfunction.

Aged↗
PubMed1997

Prediction of the changes in cardiac output in association with preload reduction therapy in patients with hypertensive heart failure.

In treating patients with acute hypertensive heart failure we often try preload-reduction therapy using diuretics or vasodilators, but this may frequently produce a considerable decrease in cardiac output, particularly in hypertensive patients with diastolic dysfunction. Therefore, it is important from the clinical standpoint to predict the change in cardiac output following preload-reduction therapy. The objective of this study was to assess whether the change in cardiac output in association with preload-reduction therapy is predictable before treatment by analysis of mitral flow velocity patterns in patients with hypertensive heart failure. Changes in left ventricular volumes and cardiac output in association with preload-reduction therapy and Doppler echocardiographic parameters of the mitral flow velocity pattern before treatment were studied in 18 patients with hypertensive heart failure. Cardiac output increased in six patients with systolic dysfunction (fractional shortening < 25%). In the other 12 patients (those with normal systolic function), the changes in cardiac output were homogenous among the patients. In this subset there was a greater decrease in cardiac output in patients with a shorter deceleration time. Thus, analysis of deceleration time of the early diastolic filling wave before treatment may be useful in estimating the change in cardiac output following preload reduction in patients with hypertensive heart failure due to diastolic dysfunction.

Adult↗
PubMed2001

Utility of B-natriuretic peptide as a rapid, point-of-care test for screening patients undergoing echocardiography to determine left ventricular dysfunction.

BACKGROUND: Although echocardiography is an important tool for making the diagnosis of left ventricular (LV) dysfunction, the cost of this procedure limits its use as a routine screening tool for this purpose. Brain natriuretic peptide (BNP) accurately reflects ventricular pressure, and preliminary studies have found it to be highly sensitive and highly specific in diagnosing congestive heart failure in the emergency department. We hypothesized that BNP might therefore be useful as a screening tool before echocardiography in patients with suspected LV dysfunction. METHODS: Subjects included patients referred for echocardiography to evaluate the presence or absence of LV dysfunction. Patients with known LV dysfunction were excluded from analysis. BNP was measured by a point-of-care immunoassay (Biosite Diagnostics, San Diego, Calif). The results of BNP levels were blinded from cardiologists making the assessment of LV function. Patients were divided into those with normal ventricular function, abnormal systolic ventricular function, abnormal diastolic function, and evidence of both systolic and diastolic dysfunction. RESULTS: Two hundred patients in whom LV function was unknown were studied. In the 105 patients (53%) whose ventricular function was subsequently determined to be normal by echocardiography, BNP levels averaged 37 +/- 6 pg/mL. This was significantly less than in those patients with either ultimate diastolic dysfunction (BNP 391 +/- 89 pg/mL (P <.001) or systolic dysfunction (BNP 572 +/- 115 pg/mL (P <.001). A receiver-operator characteristic curve showing the sensitivity and specificity of BNP against the echocardiography diagnosis revealed the area under the curve (accuracy) was 0.95. At a BNP level of 75 pg/mL was 98% specific for detecting the presence or absence of LV dysfunction by echocardiography. CONCLUSIONS: A simple, rapid test for BNP, which can be performed at the bedside or in the clinic, can reliably predict the presence or absence of LV dysfunction on echocardiogram. The data indicate that BNP may be an excellent screening tool for LV dysfunction and may, in fact, preclude the need for echocardiography in many patients.

Aged↗
PubMedDate not supplied

Scleroderma heart disease.

Heart disease is a frequent and often severe feature of systemic sclerosis (scleroderma). Cardiomyopathy, with ventricular diastolic dysfunction and arrhythmias, is the most important form, since it is associated with a very poor prognosis. The current challenge is to define its pattern and identify individuals at risk, but evaluation in vivo may be hard to perform. The aim of this review is to provide an update on the clinical aspects of scleroderma heart disease and the early pivotal role that coronary microcirculation dysfunction plays in its development. A discussion of the diagnostic tools now available for this frequently asymptomatic condition will be provided. Treatment options will be reviewed, even though no cure for systemic sclerosis exists, and the current therapy of diastolic dysfunction remains unsatisfactory.

Animals↗
PubMed2004

Influence of alterations in loading on mitral annular velocity by tissue Doppler echocardiography and its associated ability to predict filling pressures.

STUDY OBJECTIVES: Early diastolic mitral annular velocity (E') by tissue Doppler echocardiography (TD) has been reported to be a load-independent index of left ventricular (LV) diastolic function, allowing the early diastolic mitral inflow velocity (E)/E' ratio to be used clinically to predict LV filling pressures. However, preload independence of E' has remained controversial, and E/E' may not consistently be predictive of LV filling pressures. Our objectives were to test the hypotheses that E' is affected by preload, and that alterations of preload, afterload, and contractility also affect E/E'. DESIGN, INTERVENTIONS, AND MEASUREMENTS: An open-chest dog model was used (n = 8). High-fidelity pressure and conductance catheters were used for pressure-volume relations, and E' was obtained by pulsed TD from the apical four-chamber view. Changes in preload and afterload were induced by vena caval and partial aortic occlusions, respectively. Data were collected during control phase and during infusions of dobutamine and esmolol to alter contractility. RESULTS: E' was consistently and significantly associated with acute decreases in LV end-diastolic pressure in each dog (n = 200 beats; r = 0.93 +/- 0.06 [mean +/- SD]). Similar results occurred with dobutamine and esmolol infusions. This preload sensitivity was reflected in E/E', which was inversely (rather than directly) correlated with LV diastolic pressure (r = - 0.67). E/E' was less affected by preload when diastolic dysfunction was induced by sustained partial aortic occlusion (time constant of relaxation increased from 46 +/- 19 to 53 +/- 21 ms, p < 0.001). CONCLUSIONS: E' was significantly influenced by preload with preserved LV function and low filling pressures (< 12 mm Hg); accordingly, E/E' was less predictive of LV filling pressures in this scenario. E/E' was more predictive of LV filling pressures in the presence of diastolic dysfunction.

Animals↗
PubMed1994

Semiautomatic evaluation of left ventricular diastolic function with cine magnetic resonance imaging.

RATIONALE AND OBJECTIVES: Cine magnetic resonance (MR) imaging is a relatively new technique that can be used to study cardiac function with high spatial and temporal resolution. However, detailed functional analysis of the entire cardiac cycle with cine MR imaging is time consuming and labor intensive. We analyzed diastolic function using a semiautomatic routine that reduces the time necessary for analysis. METHODS: Twenty subjects (10 normal control subjects and 10 patients with isolated diastolic dysfunction) were examined. Short-axis cine MR images were obtained at 32 phases of the cardiac cycle. A semiautomatic boundary-finding routine was used to determine left ventricular (LV) volumes at each phase. Volume-versus-time and first-derivative curves were created from these data. Several parameters derived from the MR imaging curves were used to characterize diastole. RESULTS: Two parameters--the ratio of early peak filling rate to late peak filling rate and the percentage of filling during early diastole--perfectly distinguished subjects with LV diastolic dysfunction from the normal control subjects. The semiautomatic analysis method substantially reduced the time necessary for analyzing the MR imaging data, compared with manual analysis. CONCLUSION: Cine MR imaging, especially with time-saving techniques such as our service automatic analysis method, has promise as a research and clinical tool in evaluating LV diastolic function.

Adult↗
PubMed2005

Heart Failure with Preserved Systolic Function.

At least 30% of patients with congestive heart failure have preserved systolic function in the absence of significant valvular heart disease. These patients have diastolic dysfunction. Patients are frequently older and hypertensive. The rate of hospitalization in these patients is similar to that in patients with systolic dysfunction. Mortality is intermediate between that of patients with systolic dysfunction heart failure and normal subjects. Diagnosis requires a clear demonstration of the presence of the heart failure syndrome, normal systolic function, and the absence of valvular disease that could increase left atrial pressures. The diagnosis is supported by evidence of diastolic dysfunction that, from a practical point of view, will be provided most frequently by tissue Doppler imaging. Few randomized data are available on efficacy of therapeutic approaches. Acute treatment centers on reducing central blood volume with diuretics and nitrates and controlling heart rate, particularly in the setting of atrial fibrillation. Further treatment centers on reversing underlying pathophysiologic changes, particularly left ventricular hypertrophy. Control of hypertension and antagonism of the renin-angiotensin-aldosterone system appear to be promising therapeutic approaches.

Journal Article↗
PubMed2002

Remodelling after surgical repair of atrial septal defects within the oval fossa.

In a retrospective study, we analysed the data from 101 adults with echocardiographic follow-up after surgical repair of defects within the oval fossa at a mean age of 35 +/- 17 years; 56% of the cohort being above the age of 30 years. Mean age at follow-up was 44 +/- 18 years, and length of follow-up was up to 40 years (11 +/- 12 years). At follow-up, atrial fibrillation or flutter was present in one quarter. Dilation of the right atrium, found in 64%, of the left atrium, found in 44%, and of the right ventricle, found in 29%, were also frequent, as well as pulmonary arterial hypertension, which was found in 30%. Diminished right ventricular ejection fraction, in contrast, was very rare, found only in 1%, and abnormal left ventricular ejection fraction was not encountered. By multivariate analysis, predictors for right or left atrial, or right ventricular, dilation were age at follow-up, degree of tricuspid regurgitation, pulmonary hypertension, and/or atrial fibrillation. In a subset of 21 patients in sinus rhythm, we correlated prospectively the diastolic and systolic function of both ventricles with levels of brain natriuretic peptide, comparing values to those of 20 age-matched controls with a mean age of 46 +/- 14 years. Levels of brain natriuretic peptide were significantly higher in patients than in controls (p = 0.006), and correlated significantly with diastolic dysfunction (p = 0.007) and left atrial size (p < 0.0001). In the long-term follow-up after surgical repair of defect within the oval fossa, therefore, complete normalization of heart size and function is rare. Despite preserved systolic function, persistent diastolic dysfunction is common and is associated with elevated levels of brain natriuretic peptide, which may explain the late occurrence of atrial arrhythmias.

Adolescent↗
PubMedDate not supplied

Ambulatory blood pressure monitoring and echocardiography--noninvasive techniques for evaluation of the hypertensive patient.

Clinic blood pressure measurements have only limited ability to determine which hypertensive patients are at greatest risk of cardiovascular events. Ambulatory blood pressure monitoring allows for noninvasive measurement of blood pressure throughout the 24-hour period. This may help to clarify discrepancies between blood pressure values obtained in and out of the clinic and confirm the presence of white-coat hypertension, broadly defined as an elevated clinic blood pressure but a normal ambulatory blood pressure. Ambulatory blood pressure values have been shown to have a better relationship to cardiovascular morbidity and mortality and end-organ damage than clinic blood pressure values. Further, patients with white-coat hypertension appear to be at greater risk of cardiovascular morbidity and end-organ damage than a normotensive population, although they are at less overall risk than a hypertensive population. Hypertensive heart disease is characterized by diastolic dysfunction, increased left ventricular mass, and coronary flow abnormalities. Left ventricular hypertrophy increases the risk of coronary heart disease, congestive heart failure, stroke, ventricular arrhythmias, and sudden death. A variety of invasive and noninvasive techniques are described herein that measure left ventricular mass, diastolic function, and coronary blood flow abnormalities. Most antihypertensive treatments promote regression of left ventricular hypertrophy and reversal of diastolic dysfunction, which may decrease symptoms of congestive heart failure and improve survival.

Blood Pressure↗
PubMed1992

Congestive heart failure with normal ejection fraction. A different mechanism requiring different therapy.

Clinicians must remain undaunted when history, physical examination, and chest radiography suggest congestive heart failure but left ventricular systolic function is normal. Many of these patients have diastolic dysfunction, and standard therapy for left ventricular systolic dysfunction is often ineffectual or detrimental. Noninvasive testing is subject to many pitfalls but may confirm a clinical suspicion and provide indications to treat or to proceed with invasive testing. In the absence of clinical signs and symptoms of congestive failure, however, abnormal diastolic indexes should not be interpreted as diagnostic of diastolic dysfunction and are not an indication to treat.

Adrenergic beta-Antagonists↗