Mechanisms, diagnosis, and treatment of diastolic heart failure

Diastolic heart failure, in the absence of LV systolic dysfunction, is a common clinical condition that can be demonstrated in as many as one third of patients with congestive heart failure. Diastolic dysfunction caused by abnormalities in LV filling can be a result of many pathologic conditions, including hypertrophy, infiltrative cardiomyopathies, or myocardial ischemia. The major physiologic determinants of LV filling can be divided into cellular mechanisms, hemodynamic characteristics, and hormonal influences. Cellular mechanisms for impaired LV inactivation are determined by the handling of calcium within the myocyte during excitation-contraction-relaxation coupling. The hemodynamic characteristics of LV diastolic filling are determined by loading conditions, the time constant of isovolumic relaxation, heart rate, ventricular nonuniformity, pericardial restraint, myocardial elasticity, chamber compliance, and coronary blood flow. The sympathetic nervous system and the renin-angiotensin system are important modulators of diastolic filling, directly or indirectly. The diagnosis of heart failure is confirmed by a combination of clinical tests including invasive and noninvasive techniques, each of which has advantages and disadvantages. Treatment of medical conditions in which diastolic heart failure is a prominent component include pharmacotherapy with calcium channel antagonists, beta-adrenergic blocking agents, diuretic agents, and angiotensin-converting-enzyme inhibitors. Certain conditions associated with diastolic filling abnormalities such as pericardial disease or severe ischemic heart disease may be best managed by surgical or percutaneous intervention. Future research will include further delineation of the cellular mechanisms of active myocardial relaxation and clinical investigation into treatment directed at improving outcome.     

Myocardial hypertrophy and arterial hypertension

Myocardial hypertrophy in different cardiac diseases is considered to be an adaptive mechanism to the increase of hemodynamic load which might restore to normal radius/wall thickness ratio and consequently to normalize wall stress. However, it has been widely demonstrated that beside the hemodynamic load, other factors contribute to the development of myocardial hypertrophy. It has been shown that in hypertensive patients, functional abnormalities (increased contribution of atrial systole to total diastolic filling, increased isovolumic relaxation period, prolonged diastolic duration, slowed ventricular filling and altered diastolic distensibility) precede the development of myocardial hypertrophy. Thus, in hypertensive patients, sign and symptoms of heart failure could be manifested in absence of myocardial hypertrophy, and might be exclusively due to diastolic dysfunction (with normal systolic function). Systolic function might be involved and compromised late when focal myocardial cell death and fibrosis occur and consequently ?adequate? hypertrophy is shifted to ?inadequate?. This evolution is accompanied by morphological and functional changes of the myocardium similar to those encountered in dilated cardiomyopathy. Impairment of systolic function in ?inadequate? hypertrophy is also due to structural changes; altered ratio between sarcomers and mitochondria, increased intercapillary distance, sarcoplasmatic reticulum dysfunction, increase of collagene component with a consequent increment of wall rigidity, hypertrophy of arterial tunica media, which alters coronary flow and coronary reserve. The progression of these morpho-functional abnormalities is a very slow process, in which adaptive mechanism mediated by several enzymes and contractile protein, contribute to maintain myocardial viability. However, over the long course, disseminated focal myocardial cell necrosis and fibrosis, which is an evolving process, is considered to be the main responsible factor for the irreversible myocardial damage and systolic dysfunction in advanced myocardial inadequate hypertrophy.     

Effects of verapamil on left ventricular diastolic dysfunction

To assess the effects of verapamil on left ventricular relaxation and filling dynamics in patients with left ventricular diastolic dysfunction (LVDD), Doppler echocardiography (DE) and cardiac catheterization (Cath) were simultaneously performed in 30 cases with LVDD. The left ventricular filling and relaxation indices were measured with DE and Cath respectively, before and after intravenous injection of verapamil. The result showed that after verapamil injection all left ventricular filling measured with DE were significantly improved in all cases, while left ventricular relaxation indices showed significant improvement only in patients with hypertrophic cardiomyopathy and hypertensive heart disease but no changes in patients with old myocardial infarction. There were no significant correlations between left ventricular filling and relaxation indices. It is concluded that the major mechanism of left ventricular filling improvement induced by verapamil is the reduction of left ventricular afterload and verapamil has different therapeutic effects on LVDD with different etiology.     

Studies of left-ventricular function in anemia due to beta-thalassemia

Left-ventricular (LV) function was studied in 23 patients with anemia due to beta-thalassemia, of whom seven had thalassemia intermedia and the remainder thalassemia major. Two-thirds of the patients wih thalassemia intermedia and almost all the patients with thalassemia major were in clinical congestive heart failure. Despite this, resting measurements of ventricular size and systolic ventricular function were normal, indicating high-output cardiac failure. However, effort testing showed a flat response or decrease in the LV shortening fraction in patients with thalassemia major, and serial studies showed a decrease in the shortening fraction over a 4-yr period in some patients. LV diastolic function was studied by calculating peak LV filling rate and the pattern of LV filling in early diastole. Three patient with thalassemia major showed a pattern indicating abnormal LV distension. Since LV end-diastolic dimension was increased, volume overload was present in all patients. The results indicate that the following factors contribute to the genesis of cardiac failure in beta-thalassemia: 1) diminished response of systolic ventricular performance to exercise and later at rest; 2) ventricular volume overload; and 3) abnormal ventricular distension in diastole. Although the ventricular filling suggests abnormal LV compliance, the effect of right-ventricular volume overload or a pericardial factor cannot be excluded.     

Graduate education in primary care: the challenge

One can summarize the current status of calcium antagonists to treat heart failure as follows: Usually there is a favorable acute response to these drugs in heart failure patients but long-term effects in the patients treated with nifedipine, diltiazem, and verapamil have produced rather disappointing results. Thus, they should not be used routinely in heart failure patients. Their main problems were related to the negative inotropic effects of the drugs, the lack of reduction in ventricular filling pressure, and activation of the neurohumoral systems which have an adverse effect on cardiovascular performance, for example, renin-angiotensin. In contrast, the second-generation calcium antagonists have more selective vasodilating properties and fewer negative inotropic properties, which, I believe, justifies their use in selected heart failure patients. Unfortunately, there are no large randomized controlled long-term trials to evaluate morbidity and mortality in heart failure patients treated with these agents. One can rationalize that the symptomatic elderly patient with isolated diastolic dysfunction can be treated effectively with calcium antagonists but, once again, there are no major trials evaluating any drug in the management of patients with isolated diastolic function not due to hypertrophic cardiomyopathy. Rationale for using calcium antagonists could be best supported in patients with active ischemic heart disease and symptoms of heart failure. In this instance the coronary vasodilator effects may relieve myocardial ischemia and, by that mechanism, improve myocardial systolic and diastolic function.     

Angiotensin-converting enzyme (ACE) inhibitors revert abnormal right ventricular filling in patients with restrictive left ventricular disease

OBJECTIVES: Our aim was to determine mechanisms underlying abnormalities of right ventricular (RV) diastolic function seen in heart failure. BACKGROUND: It is not clear whether these right-sided abnormalities are due to primary RV disease or are secondary to restrictive physiology on the left side of the heart. The latter regresses with angiotensin-converting enzyme inhibition (ACE-I). METHODS: Transthoracic echo-Doppler measurements of left- and right-ventricular function in 17 patients with systolic left ventricular (LV) disease and restrictive filling before and 3 weeks after the institution of ACE-I were compared with those in 21 controls. RESULTS: Before ACE-I, LV filling was restrictive, with isovolumic relaxation time short and transmitral E wave acceleration and deceleration rates increased (p < 0.001). Right ventricular long axis amplitude and rates of change were all reduced (p < 0.001), the onset of transtricuspid Doppler was delayed by 160 ms after the pulmonary second sound versus 40 ms in normals (p < 0.001) and overall RV filling time reduced to 59% of total diastole. Right ventricular relaxation was very incoordinate and peak E wave velocity was reduced. Peak RV to right atrial (RA) pressure drop, estimated from tricuspid regurgitation, was 45+/-6 mm Hg, and peak pulmonary stroke distance was 40% lower than normal (p < 0.001). With ACE-I, LV isovolumic relaxation time lengthened, E wave acceleration and deceleration rates decreased and RV to RA pressure drop fell to 30+/-5 mm Hg (p < 0.001) versus pre-ACE-I. Right ventricular long axis dynamics did not change, but tricuspid flow started 85 ms earlier to occupy 85% of total diastole; E wave amplitude increased but acceleration and deceleration rates were unaltered. Values of long axis systolic and diastolic measurements did not change. Peak pulmonary artery velocity increased (p < 0.01). CONCLUSIONS: Abnormalities of RV filling in patients with heart failure normalize with ACE-I as restrictive filling regresses on the left. This was not due to altered right ventricular relaxation or to a fall in pulmonary artery pressure or tricuspid pressure gradient, but appears to reflect direct ventricular interaction during early diastole.     

Adverse effects and recovery after total intravenous anesthesia in children

INTRODUCTION: The asynchrony of the left ventricle--i.e., its nonuniform contraction and relaxation--is an important factor for left ventricular function. Heart failure is often related to abnormal systolic function, sometimes associated with a diastolic dysfunction. We studied the relationship of left ventricular asynchrony to left ventricular function in patients with nonischemic heart failure. MATERIAL AND METHODS: Radionuclide angiography at rest was performed in 25 patients with nonischemic heart failure and in 26 age and sex matched normal subjects. In addition to ejection fraction and peak filling rate, two indices of left ventricular asynchrony were calculated: the coefficient of variation of regional time to end systole and the coefficient of variation of regional time to peak filling rate. These factors indicate how disperse are the regional values of time to end systole and of time to peak filling rate. In fact, the higher the value, the greater the asynchrony. RESULTS: A significant (r = .46, p < .05) inverse correlation was found between the ejection fraction and the coefficient of variation of regional time to end systole in both the normal subjects and the heart failure patients, while the ejection fraction correlated significantly (r = .46, p < .05) with the coefficient of variation of regional time to peak filling rate only in the patients. Moreover, the peak filling rate was inversely correlated (r = .57, p < .05) with the coefficient of variation of regional time to peak filling rate in the heart failure patients but not in the normal subjects. CONCLUSIONS: These results suggest that left ventricular systolic and diastolic asynchrony may contribute to impair left ventricular systolic and diastolic function in patients with nonischemic heart failure.     

Effects of obesity and weight loss on cardiac function and valvular performance

OBJECTIVE: To study the consequences of long-standing obesity on myocardial function and valvular performance and to determine the effects of weight loss on these cardiovascular features. RESEARCH METHODS AND PROCEDURES: We included 41 patients with obesity referred for weight-reducing gastroplasty, 31 patients with obesity who received dietary recommendations, and 43 lean subjects. Body weight and blood pressure were measured, and cardiac function and valvular performance were estimated echocardiographically. Left ventricular ejection fraction was used to assess systolic heart function, and the ratio of transmitral early to atrial (E/A) peak flow velocity was used as an estimate of diastolic filling. All three study groups were investigated at baseline, and the two groups with obesity were re-examined at 1-year follow-up. RESULTS: Patients with obesity had higher blood pressure, greater cardiac output, lower ejection fraction, and reduced E/A ratio, compared with lean subjects (p<0.01). Surgical treatment of obesity led to significant decreases in body weight, whereas body weight remained unchanged in the group treated with dietary recommendations (p<0.001). In the weight loss group, blood pressure and cardiac output decreased and the E/A ratio increased (p<0.001). Left ventricular ejection fraction tended to increase in the weight loss group and decrease in the obese control group (p<0.01). No significant valvular disease was observed in any of the subjects with obesity at baseline or after weight loss. DISCUSSION: We conclude that weight reduction in subjects with obesity is associated with improvements in left ventricular diastolic filling and has favorable effects on left ventricular ejection fraction. Neither obesity nor weight loss seem to promote valvular heart disease.     

New aspects of the treatment of left ventricular failure: Nitroglycerin (author's transl)

The effectiveness of Nitroglycerin and its derivates in angina pectoris is well-known. One of the main effects is the reduction of left ventricular filling pressure. Therefore in patients with left ventricular failure after acute myocardial infarction or with chronic coronary heart disease the indication for Nitroglycerin has to be proved. In 51 patients with 76 measurements Nitroglycerin sublingual, intravenous Nitroglycerin, Isosorbide-Dinitrate and Myocardon were investigated. All substances decreased pulmonary artery pressure especially left ventricular filling pressure. Cardiac output increased or decreased in dependence to the height of left ventricular enddiastolic pressure. In the patients with myocardial infarction and left ventricular failure with filling pressures over 20 mm Hg a significant increase in cardiac output was observed. On the contrary in patients without left ventricular failure cardiac output decreased slightly. Nitroglycerin sublingual is especially useful in the most severe form of left ventricular failure: in pulmonary oedema. 0.8 mg of Nitroglycerin 3 to 4 times in 5 to 10 minutes distance is necessary dependent on the severity of the pulmonary oedema and the height of the blood pressure. The permanent intravenous infusion of Nitroglycerin (3 to 6 mg per hour) is very efficient in the treatment of congestive failure in acute myocardial infarction. The left ventricular filling pressure decreased from 28 to 16 mm Hg with an increase in cardiac output from 3.5 to 4.01/min. The mean arterial pressure dropped about 10 mm Hg. Also with oral derivates of Nitroglycerin (Isosorbide-Dinitrate and Myocardon) an extensive decrease in left ventricular filling pressure and an increase in cardiac output has been observed in patients with left heart failure.     

Superiority of brain natriuretic peptide as a hormonal marker of ventricular systolic and diastolic dysfunction and ventricular hypertrophy

Atrial and brain natriuretic peptides (ANP and BNP) are produced by the heart, and their plasma concentrations are increased in human chronic congestive heart failure. Although separate studies have suggested that circulating levels of the biologically active C-terminal ANP, the biologically inactive N-terminal ANP, and BNP may have diagnostic utility in the detection of left ventricular systolic dysfunction or left ventricular hypertrophy, no studies have directly assessed the relative value of these peptides prospectively. We therefore designed this study to compare the relative ability of the different natriuretic peptides to detect abnormal left ventricular systolic and diastolic function and left ventricular hypertrophy. Using a prospective study design, we investigated 94 patients referred for cardiac catheterization and 15 age-matched normal subjects. The diagnostic abilities of elevated plasma C-terminal ANP, N-terminal ANP-(1-30), and BNP concentrations to identify systolic dysfunction (ejection fraction < 45%), diastolic dysfunction (time constant of left ventricular relaxation > 55 milliseconds, left ventricular end-diastolic pressure > 18 mm Hg), and left ventricular hypertrophy (left ventricular mass index > 120 g/m2) were objectively compared by receiver operating characteristic analysis. The areas under the receiver operating characteristic curve of BNP for detecting each of these abnormalities ranged from 0.715 to 0.908 and were significantly greater than those of C-terminal ANP or N-terminal ANP-(1-30). The sensitivity and specificity of an elevated plasma BNP, which we defined as greater than the mean + 3 SD of the 15 age-matched normal subjects, were 0.83 and 0.77, respectively, for detecting ejection fraction less than 45%, 0.85 and 0.70 for detecting the time constant of left ventricular relaxation greater than 55 milliseconds, 0.63 and 0.76 for detecting left ventricular end-diastolic pressure greater than 18 mm Hg, and 0.81 and 0.85 for detecting left ventricular mass index greater than 120 g/m2. The use of BNP and one other peptide increased sensitivity (0.90 to 0.96), albeit with lower specificity (0.56 to 0.71). An elevated plasma BNP was a more powerful marker of left ventricular systolic dysfunction, left ventricular diastolic dysfunction, and left ventricular hypertrophy than C-terminal ANP or N-terminal ANP-(1-30) in this population of patients with suspected cardiac disease. Measurement of BNP alone or in combination with C-terminal ANP or N-terminal ANP-(1-30) has potential utility for the detection of altered left ventricular structure and function in a patient population at risk for cardiovascular disease.     

Coupled systolic-ventricular and vascular stiffening with age: implications for pressure regulation and cardiac reserve in the elderly

OBJECTIVES: We tested the hypothesis that age-related arterial stiffening is matched by ventricular systolic stiffening, and that both enhance systolic pressure sensitivity to altered cardiac preload. BACKGROUND: Arterial rigidity with age likely enhances blood pressure sensitivity to ventricular filling volume shifts. Tandem increases in ventricular systolic stiffness may also occur and could potentially enhance this sensitivity. METHODS: Invasive left ventricular pressure-volume relations were measured by conductance catheter in 57 adults aged 19 to 93 years. Patients had normal heart function and no cardiac hypertrophy and were referred for catheterization to evaluate chest pain. Twenty-eight subjects had normal coronary angiography and hemodynamics, and the remaining had either systolic hypertension or coronary artery disease without infarction. Data recorded at rest and during transient preload reduction by inferior vena caval obstruction yielded systolic and diastolic left ventricular chamber and effective arterial stiffness and pulse pressure. RESULTS: Left ventricular volumes, ejection fraction and heart rate were unaltered by age, whereas vascular load and stiffening increased (p < 0.008). Arterial stiffening (Ea) was matched by increased ventricular systolic stiffness (Ees): Ees=0.91 x Ea + 0.53, (r=0.50, p < 0.0001), maintaining arterial-heart interaction (Ea/Ees ratio) age-independent. Ventricular systolic and diastolic stiffnesses correlated (r=0.51, p < 0.0001) and increased with age (p < 0.03). Both ventricular and vascular stiffening significantly increased systolic pressure sensitivity to cardiac preload (p < 0.006). CONCLUSIONS: Arterial stiffening with age is matched by ventricular systolic stiffening even without hypertrophy. The two effects contribute to elevating systolic pressure sensitivity to altered chamber filling. In addition to recognized baroreflex and autonomic dysfunction with age, combined stiffening could further enhance pressure lability with diuretics and postural shifts in the elderly.     

Hypertension in the elderly: age- and disease-related complications and therapeutic implications

Effective treatment of hypertension in the elderly requires an understanding of both the progressive course of the disease and the impact of aging on the cardiovascular system, including physiological, genetic, lifestyle, and environmental factors. Review of the literature that has attempted to define the impact of an "aging process" on cardiovascular structure and function reveals a diversity of findings and interpretations. However, in general, normotensive elderly subjects exhibit the heart and vascular characteristics of "muted" hypertension, including many features of younger hypertensive patients: cardiac hypertrophy, diminution in resting left ventricular early diastolic filling rate, increased arterial stiffness and aortic impedance, diminution in the baroreceptor reflex, a diminished response to catecholamines and diminished renal blood flow, and an increase in peripheral vascular resistance (PVR). Treatment of elderly hypertensives is more challenging because of the greater likelihood of the presence of concomitant diseases, most importantly, coronary and peripheral atherosclerosis, renal dysfunction, and diabetes mellitus. Isolated systolic hypertension (ISH), the most common form of hypertension in the elderly, has also been clearly shown to be an important predictor of cardiovascular morbidity and mortality, including coronary artery disease, congestive heart failure, and stroke. Treatment of ISH has been shown to lower systolic pressure safely and effectively in the elderly. By reducing PVR, and possibly the arterial stiffness, and thus the early reflected pulse waves, vasodilators, including calcium antagonists, may lower these three components of arterial impedance, and hence lower the arterial load on the heart. The cardiac hypertrophy and reduced left ventricular filling rate associated with hypertension in older individuals can also be ameliorated, to some extent, by calcium channel blockers.     

ACE inhibitors unmask incoordinate diastolic wall motion in restrictive left ventricular disease

OBJECTIVE: To assess the effect of ACE-inhibition on left ventricular filling and wall motion in patients with a clinical diagnosis of heart failure. DESIGN: Prospective examination of left ventricular systolic and diastolic function using M mode echocardiography and pulsed and continuous wave Doppler before and three weeks after starting an ACE inhibitor. SETTING: A tertiary referral centre for cardiac disease equipped with non-invasive facilities. SUBJECTS: 30 outpatients with a clinical diagnosis of heart failure in whom treatment with an ACE inhibitor was started; age 61 (SD 11) years; 27 male; 3 female; 21 healthy controls of similar age. RESULTS: Left ventricular cavity was dilated both at end systole and end diastole, and fractional shortening reduced. Although mean isovolumetric relaxation time (IVRT) and transmitral E (early) to A (late) filling velocity (E/A) ratio were not different from normal, a value of 1.0 on the normal frequency plot of the E/A ratio divided the patients bimodally into two groups: 20 patients (group A) with E/A ratio > 1.0 and 10 patients (group B) < 1.0. In group A patients, IVRT was short as was transmitral E wave deceleration time compared to normal (P < 0.001), fulfilling the criteria of restrictive left ventricular physiology. Left ventricular wall motion during IVRT was coordinate and left ventricular end diastolic pressure was raised on the apex-cardiogram (P < 0.001). In group B, E wave deceleration time was longer, relaxation incoordinate, and apexcardiogram normal. With an ACE inhibitor: in group A, left ventricular dimensions fell at end diastole (P < 0.05) and end systole (P < 0.01) but fractional shortening did not change; long axis total excursion (P < 0.01) and peak rate of shortening (P < 0.05) both increased; IVRT increased (P < 0.001) with the appearance of markedly incoordinate wall motion, minor axis lengthening, and long axis shortening (P < 0.001 for both); A wave amplitude also consistently increased (P < 0.001); finally, transmitral E wave velocity fell and A wave velocity increased. ACE inhibition did not alter any of the left ventricular minor and long axis or transmitral Doppler variables in patients in group B. CONCLUSIONS: Patients with a clinical diagnosis of heart failure differ in their presentation and response to ACE inhibition according to baseline haemodynamics. In restrictive left ventricular physiology, ACE inhibition reduces cavity size and prolongs IVRT, compatible with a fall in left atrial pressure. At the same time, ventricular relaxation becomes very delayed and incoordinate, greatly reducing early diastolic left ventricular filling velocity. Thus ACE inhibition unmasks major diastolic abnormalities in patients with restrictive left ventricular disease.     

Congestive heart failure in patients with valvular aortic stenosis. A clinical and echocardiographic Doppler study

The aim of this study was to evaluate echographically anatomic and functional features of the left ventricle in adult patients with valvular aortic stenosis according to the presence or absence of congestive heart failure and the level of ventricular performance. Fifty-six adult patients with moderate-to-severe aortic stenosis underwent echocardiographic Doppler examination in order to evaluate left ventricular mass and dimensions, systolic function and filling dynamics. Twenty-seven patients had no heart failure and were symptomatic for angina (5), syncope (4) or were symptom-free (group I); the other 29 had heart failure (group II): 16 with normal left ventricular systolic performance (fractional shortening > 25%, group IIa) and 13 with systolic dysfunction (fractional shortening < or = 25%, group IIb). Despite a similar left ventricular mass, compared to group IIa, group IIb showed a significant left ventricular dilatation (end-diastolic diameter: 61 +/- 6.5 vs. 45.5 +/- 6.1 mm, p < 0.001) and mild or no increase in wall thickness (11.5 +/- 1.6 vs. 14.9 +/- 2 mm, p < 0.001). Indices of left ventricular filling on Doppler transmitral flow were also significantly different between the two groups, with a higher early-to-late filling ratio and a shorter deceleration time of early filling in group IIb (2.8 +/- 1.9 vs. 1.2 +/- 0.85, p < 0.01, and 122 +/- 66 vs. 190 +/- 87 ms, p < 0.05, respectively), both indirectly indicating higher left atrial pressure. Finally, heart failure was generally more severe in group IIb patients. In some patients with aortic stenosis, symptoms of heart failure may be present despite a normal left ventricular systolic function and seem to depend on abnormalities of diastolic function. The presence of systolic or isolated diastolic dysfunction appears to be related to a different geometric adaptation of the left ventricle to chronic pressure overload.     

Anti-metastatic and immunomodulating properties of the water extract from Celosia argentea seeds

Although dynamic cardiomyoplasty (DCMP) is currently being evaluated as an alternative to end-stage congestive heart failure, the overall results of DCMP are variable and inconclusive. We evaluated the effect of classic DCMP on systolic and diastolic cardiac function in normal heart using reliable indicators which minimize the influences of load conditions. Six experimental dogs were evaluated with the acute nonpreconditioning model. The slope of the linear preload recruitable stroke work relationship (Mw) showed a significant increase with latissimus dorsi muscle (LDM) stimulation (postwrap non-stimulation 59.1+/-6.3, postwrap stimulation 98.6+/-9.7 erg cm(-3) x 10(3); P < 0.01), and the x-intercept (V0) was unchanged; these were utilized as the indicators of left ventricular systolic function. The constant of pressure decay (tau) increased after LDM wrap (prewrap 45.8+/-6.0, postwrap nonstimulation 69.3+/-10.3, postwrap stimulation 72.3+/-13.9 ms; P < 0.05), and the peak filling rate was unchanged after LDM wrap, which were utilized as the indicators of diastolic function. We concluded that classic dynamic cardiomyoplasty is effective in assisting systolic cardiac function, but may to some degree have a detrimental effect on the diastolic cardiac function.     

Cervical intraepithelial neoplasia in adolescents: study of cytological findings between 1987 and 1995 in S?o Paulo State-Brazil

Cardiovascular complications are the most common causes of morbidity and mortality in diabetic patients. Coronary atherosclerosis is enhanced in diabetics, whereas myocardial infarction represents 20% of deaths of diabetic subjects. Furthermore, re-infarction and heart failure are more common in the diabetics. Diabetic cardiomyopathy is characterized by an early diastolic dysfunction and a later systolic one, with intracellular retention of calcium and sodium and loss of potassium. In addition, diabetes mellitus accelerates the development of left ventricular hypertrophy in hypertensive patients and increases cardiovascular mortality and morbidity. Treating the cardiovascular problems in diabetics must be undertaken with caution. Special consideration must be given with respect to the ionic and metabolic changes associated with diabetes. For example, although ACE inhibitors and calcium channel blockers are suitable agents, potassium channel openers cause myocardial preconditioning and decrease the infarct size in animal models, but they inhibit the insulin release after glucose administration in healthy subjects. Furthermore, potassium channel blockers abolish myocardial preconditioning and increase infarct size in animal models, but they protect the heart from the fatal arrhythmias induced by ischemia and reperfusion which may be important in diabetes. For example, diabetic peripheral neuropathy usually presents with silent ischemia and infarction. Mechanistically, parasympathetic cardiac nerve dysfunction, expressed as increased resting heart rate and decreased respiratory variation in heart rate, is more frequent than the sympathetic cardiac nerve dysfunction expressed as a decrease in the heart rate rise during standing.     

Age-related alteration of proline hydroxylase and collagen-binding heat shock protein (HSP47) expression in human fibroblasts

It is now well recognized that a disorder of left ventricular filling can be sufficient to account for congestive heart failure. Furthermore, evaluation of heart disease would not be complete if it did not include assessment of left ventricular filling, improvement of which probably ensures better control of the heart disease. An efficient and reliable tool for the study of diastolic function is therefore essential. The authors review the current state of knowledge and the more recent developments in Doppler echocardiography in the evaluation of left ventricular diastolic function. After revising the pathophysiology, the methods of studying ventricular filling are described. The recording technique is described, taking into account recent developments in transthoracic and transoesophageal approaches. This investigation provides parameters allowing semiquantitative estimation of filling pressures (mean left atrial pressure, end-diastolic pressure) and reliable evaluation of overall diastolic performance.     

The age-associated alterations in late diastolic function in mice are improved by caloric restriction

Caloric restriction reduces the magnitude of many age-related changes in rodents. Cardiac function is altered with senescence in mice, rats, and healthy humans. We examined the effects of life-long caloric restriction on diastolic and systolic cardiac function in situ using Doppler techniques in ad libitum-fed 30- to 32-month-old (AL) and calorically restricted (CR) 32- to 35-month-old female B6D2-F1 hybrid mice. The heart weight to body weight ratio was similar in AL (5.74 +/- .24 mg/g) and CR (5.68 +/- .20 mg/g) mice. Two systolic functional parameters known to decrease with age in both humans and mice, peak aortic velocity and aortic acceleration, were unchanged by CR compared to AL. In contrast, diastolic function was altered by caloric restriction. Although left ventricular peak early filling velocity (E) was not different between CR and AL, peak atrial filling velocity (A) was 50% lower in CR compared to AL (p < .001). The ratio of early diastolic filling to atrial filling (E/A ratio) was 64% higher in the CR (2.74 +/- .31) than the AL (1.55 +/- .07; p = .004). The fraction of ventricular filling due to atrial systole, the atrial filling fraction, was also reduced in CR (.21 +/- .04) compared to AL (.36 +/- .02; p = .007). These changes occurred in CR without alteration in E deceleration time, which is consistent with improved diastolic function in CR. Through mechanisms that remain unknown, lifelong caloric restriction may prevent the age-related impairments in late diastolic function but does not alter the impairments in systolic or early diastolic cardiac function.     

Intravenous nitroglycerin in acute respiratory failure of patients with chronic obstructive lung disease, secondary pulmonary hypertension and cor pulmonale

We have studied the hemodynamic effects of an intravenous single dose of nitroglycerin in 13 patients with secondary pulmonary hypertension and Cor Pulmonale, during the acute course of respiratory failure and under assisted ventilation. We observed a significant decrease in systolic, diastolic and mean pulmonary arterial pressures, and in pulmonary resistance and systolic right ventricular work index, without any change in right or left pre-loads. The systolic arterial pressure decreased slightly, without any change in cardiac index or diastolic pressure. The arterial and mixed venous oxygen contents, and the pulmonary shunting ( Qs/Qt) were unchanged. These results suggest that nitroglycerin may be a useful therapy in patients in the acute stages of pulmonary hypertension resulting from chronic lung disease and under assisted ventilation. In addition, the lack of change in cardiac index, intrapulmonary shunting and oxygen content suggests that this decrease in pulmonary resistance is not linked with any deleterious effect in oxygen transfer.     

Early effects of coronary artery bypass surgery and cold cardioplegic ischemia on left ventricular diastolic function: evaluation by computer-assisted transesophageal echocardiography

OBJECTIVE: Although left ventricular (LV) systolic function undergoes a temporary decrease after cardiopulmonary bypass (CPB) in patients undergoing coronary artery bypass grafting (CABG), data on the effects of CABG and cardioplegic arrest on LV diastolic function are contradictory. The objective of the present study was to further evaluate the effects of CABG and CPB on LV diastolic function. DESIGN: A prospective study. SETTING: A multi-institutional investigation at a university hospital. PARTICIPANTS: 20 patients on beta-receptor antagonists, scheduled for CABG and with a preoperative ejection fraction over 0.5. INTERVENTIONS: Central hemodynamic measurements, transesophageal LV short-axis images, and mitral Doppler flow profiles were obtained before and after volume loading that in turn was performed both before surgical incision and after weaning from CPB. MEASUREMENTS AND MAIN RESULTS: Heart rate, cardiac output, and peak atrial filling velocity increased; systemic vascular resistance decreased; whereas stroke volume, LV area ejection fraction, deceleration rate and slope of early diastolic filling, time-velocity integral of early diastolic filling, and the ratio between early and atrial peak filling velocity were unchanged post-CPB compared with pre-CPB. LV end-diastolic stiffness that was calculated for each patient pre-CPB and post-CPB using the formula: P = B*eS*A), where P is the LV filling pressure and A is the end-diastolic short-axis area, was unchanged post-CPB compared with pre-CPB. CONCLUSIONS: Both the active and passive components of LV diastolic function are well maintained shortly after CABG and cardioplegic arrest in patients with a good preoperative systolic LV function.