Preclinical cardiac dysfunction in transfusion-dependent children and young adults detected with low-dose dobutamine stress echocardiography

Transfusion-dependent (TD) patients develop cardiac iron overload that will eventually lead to cardiac pump failure. Low-dose dobutamine stress echocardiography may complement resting echocardiography and identify preclinical myocardial dysfunction caused by early cardiac hemosiderosis. Twenty-six iron-overloaded TD patients had stress echocardiography with 5 microg/kg per minute of dobutamine. Indexed left ventricular (LV) mass, LV dimensions, meridional wall stress, and cardiac index were significantly increased. TD patients had similar LV shortening fraction by M-mode (40.5% +/- 5.6% vs 39.4% +/- 4.5%) but had a lower mean LV ejection fraction (53.3% +/- 3.9% vs 46.8% +/- 6.9%, P < .002) and a subnormal increase in cardiac index during dobutamine stress (35% +/- 20% vs 11% +/- 16%, P < .0001). Impairment in LV relaxation was demonstrated by a prolonged isovolumetric relaxation time (0.060 +/- 0.005 vs 0.088 +/- 0.019 seconds, P < .0001), increased peak mitral E wave, and abnormal E/A ratio. Asymptomatic TD patients demonstrate decreased systolic functional reserve and abnormal left ventricular relaxation that may be caused by cardiac hemosiderosis. Low-dose dobutamine stress echocardiography may be useful for detecting and following cardiac dysfunction in patients at risk for cardiac hemosiderosis.     

A novel monoclonal antibody permitting recognition of NKT cells in various mouse strains

OBJECTIVES: The purpose of this study was to determine whether restrictive left ventricular (LV) filling patterns are associated with diastolic ventricular interaction in patients with chronic heart failure. BACKGROUND: We recently demonstrated a diastolic ventricular interaction in approximately 50% of a series of patients with chronic heart failure, as evidenced by paradoxic increases in LV end-diastolic volume despite reductions in right ventricular end-diastolic volume during volume unloading achieved by lower body negative pressure (LBNP). We reasoned that such an interaction would impede LV filling in mid and late diastole, but would be minimal in early diastole, resulting in a restrictive LV filling pattern. METHODS: Transmitral flow was assessed using pulsed wave Doppler echocardiography in 30 patients with chronic heart failure and an LV ejection fraction < or = 35%. Peak early (E) and atrial (A) filling velocities and E wave deceleration time were measured. Left ventricular end-diastolic volume was measured using radionuclide ventriculography before and during -30-mm Hg LBNP. RESULTS: Nine of the 11 patients with and 2 of the 16 patients without restrictive LV filling patterns (E/A > 2 or E/A 1 to 2 and E wave deceleration time < or = 140 ms) increased LV end-diastolic volume during LBNP (p = 0.001). The change in LV end-diastolic volume during LBNP was correlated with the baseline A wave velocity (r = -0.52, p = 0.005) and E/A ratio (r = 0.50, p = 0.01). CONCLUSIONS: Restrictive LV filling patterns are associated with diastolic ventricular interaction in patients with chronic heart failure. Volume unloading in the setting of diastolic ventricular interaction allows for increased LV filling. Identifying patients with chronic heart failure and restrictive filling patterns may therefore indicate a group likely to benefit from additional vasodilator therapy.     

MRI-derived ventricular volume curves for the assessment of left ventricular function

To assess the utility of double oblique, ECG-gated 1H magnetic resonance (MR) derived volume curves for assessing LV function, cardiac short axis images were acquired with a fast field echo technique. We applied this methodology to assess left ventricular function in three groups: normals, patients with left ventricular hypertrophy, and dilated cardiomyopathy. Six slices with 16-20 phases per RR interval were analyzed, representing the initial 75-80% of the cardiac cycle. For each slice, the endocardial border of the left ventricular (LV) chamber was manually traced. Using Simpson's rule, the total LV volume at a given phase was determined considering the traced area, thickness and position in three-dimensional space of each of the six constituent slices. The calculated volumes were plotted against time and the stroke volume, ejection fraction and cardiac output were determined. The volume vs time plots for the systolic and diastolic portions of the curve were individually fit to third degree polynomials using a least squares approximation. From the fit curves, the following data were extracted: the mean slope (dV/dT) during filling and emptying, and the time to 1/4, 1/3 and 1/2 filling and emptying. These parameters are valuable indices of the functional status of the myocardium; thus, accurate and useful estimates of LV function can be obtained using MRI derived volume curves in normal and abnormal states.     

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.     

Exercise capacity in patients with beta-thalassemia major: relation to left ventricular and atrial size and function

OBJECTIVES: The objective of this study was to examine the association between exercise capacity and echocardiographic indexes of atrial and ventricular function and size in patients with beta-thalassemia major. BACKGROUND: In patients with beta-thalassemia major, the assessment of cardiac function with echocardiography alone does not always correspond to their functional status. Peak oxygen uptake and anaerobic threshold, on the other hand, constitute 2 objective and reproducible determinants of exercise capacity in patients with heart failure. METHODS AND RESULTS: Forty consecutive patients (22 women and 18 men, 18 to 30 years old) who were in stable condition while receiving regular transfusions and 30 age- and sex-matched control subjects were studied. At 2 to 3 days after the last transfusion, each subject underwent complete echocardiographic study followed by cardiopulmonary exercise testing. Left atrial volumes (maximal [Vmax], at onset of atrial systolic [Vp], and minimal [Vmin]) and left ventricular volumes were measured with the biplane area-length method, and left atrial active emptying fraction (ACTEF) and left ventricular ejection (LVEF) fraction were calculated. Peak oxygen uptake (Vo 2 max) and anaerobic threshold (AT) were also estimated. After transfusion, patients with beta-thalassemia major had reduced Vo 2 max and AT and greater left atrial volume in comparison with control subjects. Also, ACTEF and LVEF were significantly lower in the patient group. Moreover, Vo2 max and AT were inversely related to Vmax (r = -0.74 and r = -0.80, respectively) and directly related to ACTEF (r = 0.85 and r = 0.82, respectively) in beta-thalassemia major, whereas they were poorly related to LVEF (r = 0.50 and r = 0. 53, respectively). In the control group, Vo 2 max and AT parameters were related to Vmax and ACTEF in a similar way to that in the beta-thalassemia group. CONCLUSIONS: In patients with beta-thalassemia major, exercise capacity does not correlate with left ventricular dimensions and function. On the contrary, left atrial size and systolic dysfunction are probably predictors of decreased exercise capacity.     

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.     

Influence of heart rate on stroke volume variability in atrial fibrillation in patients with normal and impaired left ventricular function

Both resting tachycardia and irregular ventricular rhythm may contribute to impaired cardiac performance in atrial fibrillation (AF). This study assesses the relation between resting heart rate and beat-to-beat changes in left ventricular (LV) ejection and filling in patients with normal and impaired LV systolic function. Beat-to-beat variation in LV outflow and inflow velocity-time integral was measured using pulsed Doppler ultrasound in 39 patients with chronic AF and normal (n=22) or impaired (n=17) LV systolic function. Aortic velocity-time integral variability increased with mean heart rate (p=0.003) even though RR interval variability decreased (p <0.001). Aortic velocity-time integral was more sensitive to the duration of both the preceding (p <0.001) and prepreceding (p <0.001) RR intervals at higher heart rates. These relations were similar for patients with normal and impaired LV systolic function. The sensitivity of the filling velocity-time integral to RR interval variability also increased with heart rate (p <0.001). However, at higher heart rates the filling velocity-time integral (p=0.009) and filling time (p=0.005) were less sensitive to change in RR intervals in patients with impaired LV function. We conclude that beat-to-beat stroke volume variability in AF increases with heart rate. Stroke volume variability was not influenced by LV systolic function.     

Left ventricular diastolic function: physiology, methods of assessment, and clinical significance

Diastole, that portion of the cardiac cycle that begins with isovolumic relaxation and ends with mitral valve closure, results in ventricular filling and involves both active (energy-dependent) and passive processes. The interactions between active processes (myocardial relaxation) that primarily influence early ventricular filling and passive processes, such as loading conditions, myocardial compliance, and valvular disease, are complex. Clinical methods to assess ventricular filling include cardiac catheterization, radionuclide angiography, and echocardiography. Any measurements of diastolic function must be made with an understanding of the determinants of ventricular filling and the limitations of the diagnostic test. Many cardiac disorders are characterized by elevated pulmonary venous pressures in the face of normal systolic ventricular function, which suggests a primary abnormality of diastolic function. Abnormalities in diastolic function have been observed in coronary artery disease, congestive heart failure (with and without systolic dysfunction), hypertrophic cardiomyopathy, hypertension, and in healthy elderly subjects. Identification of these abnormalities may be useful clinically, particularly in patients with symptoms of heart failure and normal systolic function. Data are not available to determine the optimal therapy for such patients, although evidence suggests that calcium channel blockers, beta blockers, and agents that reverse myocardial hypertrophy may be useful. This review briefly summarizes the physiology of diastole, the methods of clinical assessment of diastolic function, and the role of diastolic function in cardiovascular disease.     

Midwall fractional shortening is an independent predictor of left ventricular diastolic dysfunction in asymptomatic patients with systemic hypertension

Conventional measures of left ventricular (LV) systolic performance suggest that diastolic dysfunction precedes the development of systolic dysfunction in hypertension. Midwall fractional shortening is a new measure of systolic function that identifies hypertensive patients who have evidence of target-organ damage, impaired contractile reserve, and increased mortality. We therefore sought to determine whether depressed midwall fiber shortening is associated with abnormal diastolic function. Echocardiograms were obtained in 102 otherwise healthy hypertensive patients without treatment with normal conventional measures of systolic function. Of these, 15 had depressed midwall shortening based on previously described normative relations. Patients with depressed midwall shortening had slightly higher blood pressure. Abnormal diastolic function, defined as late (A) LV inflow velocity greater than early (E) velocity, was observed in 33% of those with normal midwall shortening but in 60% of those with depressed shortening (p <0.05). Patients with A/E >1 had lower absolute midwall fiber shortening (15 +/- 3% vs 18 +/- 3%, p <0.0001) but similar endocardial shortening. Patients with abnormal midwall shortening had higher A/E and longer isovolumic relaxation times (both p <0.05). In multivariate analysis, midwall fractional shortening, age, and heart rate were independent predictors (p <0.01) of A/E in a model including blood pressure, LV mass, and endocardial shortening. We conclude that subnormal midwall shortening predicts LV diastolic abnormalities in this population of hypertensive patients with otherwise normal measures of LV systolic function. Contrary to our previous understanding, depressed LV systolic performance, when identified with this newer method, occurs coincidentally with impaired diastolic function.     

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.     

Left ventricular function by echocardiography in children with fixed aortic stenosis

Left ventricular function was evaluated echocardiographically within 24 hours of cardiac catheterization in 45 children with fixed aortic stenosis. Left ventricular systolic time intervals, mean velocity of circumferential fiber shortening, left ventricular end-diastolic volume and shortening fraction were evaluated. Some patients with severe aortic stenosis had a shortened preejection period, prolonged ejection time and increased mean velocity of circumferential fiber shortening in comparison with normal subjects, but these findings were not consistent within the group with severe aortic stenosis or apparent in patients with mild or moderate aortic stenosis. Left ventricular end-diastolic volume was smaller in children with severe obstruction than in normal children. Evaluation of the shortening fraction provided good separation of patients with significant obstruction from those with mild disease. Further, there was a linear correlation between the shortening fraction and the left ventricular-aortic gradient demonstrated at cardiac catheterization. This correlation was also of use in evaluating the response of patients to surgical relief of obstruction. Pre- and postoperative echocardiographic evaluation of the shortening fraction appears to provide a readily available noninvasive method of assessing the course and severity of obstruction in fixed aortic stenosis in children.     

Echocardiography in the evaluation of ventricular function

The ultrasonic beam used for quantitative assessment of left ventricular (LV) function traverses the heart in a projection similar to the familiar angiographic left anterior oblique projection. It crosses the anterior wall of the right ventricle, the right ventricular cavity, the interventricular septum, the LV cavity and the posterior wall of the left ventricle. Whereas the cyclic changes of the right ventricular diameter are rarely clearly determined by echocardiography, the easily assessed cyclic changes of the LV endocardial transverse diameter are useful measure of LV FUNCTION. Of practical importance are the percentage of systolic shortening of the LV diameter (%Sh) and the mean velocity of circumferential fiber shortening (VCF). There are several factors, such as placing of the ultrasonic transducer, the shape and size of the LV cavity and rotational movements of the heart as a whole, that influence echocardiographic determination of the transverse LV diameter. In patients with asynergic contraction, %Sh and VCF cannot be used as measures of overall LV performance, but localized contraction disturbances of the septum and the posterior wall may be detected from the reduced extent of wall motion in a given LV segment during a full sweep from the base to the apex. The most important indications for echocardiographic assessment of LV function are valvar diseases with chronic LV pressure or volume overload, and congestive cardiomyopathy. Echocardiography has proved useful in serial evaluation of LV function in patients undergoing valvar heart surgery. Assessment of LV volume by standard echocardiography using the cubic formula is not satisfactory. More accurate determination of volumes is provided by formulas that include the actual ratio of the LV long axis to the minor axis.     

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.     

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.     

Reduced left ventricular hypertrophy in type 1 diabetic patients with end-stage renal failure. A comparison between groups investigated 1977-80 and 1991-93

BACKGROUND: During the last decade, control of hypertension, oedema, anaemia, uraemia, and blood glucose has improved in patients with diabetic nephropathy. We have investigated whether this has influenced cardiac function at the time of end-stage renal failure. STUDY DESIGN: Echocardiographic investigations were performed in 26 type 1 diabetic patients evaluated for kidney transplantation and the results compared with those obtained in healthy controls and in a similar group of patients investigated in 1977-1980. RESULTS: Blood pressure was 153 +/- 21/85 +/- 12 mmHg versus 174 +/- 17/91 +/- 9 (recent group versus early group). The left ventricular (LV) diameter index, a measure of volaemia, was increased in systole and diastole in the early but not in the recent group. Both groups had LV hypertrophy, but this was much less pronounced in the recent group; posterior wall thickness was 1.1 +/- 0.16 cm versus 1.3 +/- 0.26 cm (P = 0.0001) and LV mass index 132 +/- 43 g/m2 versus 166 +/- 44 g/m2 (P = 0.009). Blood pressure correlated significantly with indices of LV hypertrophy in the recent group. Systolic function was normal in both groups but diastolic function was disturbed in both and to the same extent, atrial systole contributing by 27 +/- 14% to ventricular filling. CONCLUSION: Better treatment of hypertension, fluid overload, and uraemia has led to less pronounced LV hypertrophy. The remaining correlation with blood pressure suggests that more could be gained by intensified antihypertensive treatment.     

Left ventricular diastolic stiffness in dogs with congestive cardiomyopathy and volume overload

Mean functional diastolic stiffness, an estimate of the left ventricular resistance to filling during diastole, was measured in 10 normal dogs, 7 dogs with diseases causing volume overload (patent ductus arteriosus and primary mitral valve insufficiency), and 4 dogs with idiopathic congestive cardiomyopathy. It was measured as the increase in pressure during diastole (deltaP), divided by the corresponding increase in volume (deltaV). The pressure was measured at cardiac catheterization, and the volume was derived by a cineangiocardiographic method. There was no increase in diastolic stiffness of the hearts with volume overload compared with the normal hearts, but those with cardiomyopathy had a large increase, although the end-diastolic volumes in cardiomyopathy were generally less than in volume overload.     

Apolipoprotein E epsilon4 allele as a genetic risk factor for left ventricular failure in homozygous beta-thalassemia

In homozygous beta-thalassemia, the organ damage is mainly attributed to excessive iron deposition through the formation of oxygen free radicals. Despite appropriate transfusion and chelation therapy and low ferritin levels, patients still develop organ failure, heart failure being the main cause of death. This study was designed to determine whether the decreased antioxidant activity of the apolipoprotein E (APOE) 4 allele could represent a genetic risk factor for the development of left ventricular failure (LVF) in beta-thalassemia homozygotes. A total of 251 Greek beta-thalassemia homozygotes were studied. Patients were divided in three groups: group A (n = 151) with no cardiac impairment, group C (n = 47) with LVF, and 53 patients with LV dilatation and normal LV systolic function constituted the group B. DNA was obtained from all patients, and the polymerase chain reaction was used to analyze the polymorphism at the APOE locus. The APOE allele frequencies were compared with those of a Greek control sample of 216 healthy blood donors. Patients with no cardiac impairment had an APOE 4 allele frequency (7.9%) not different from population controls (6.5%, P > .05), while patients with LVF had a significantly higher frequency of APOE 4 (12.8%) than the controls (P < .05, odds ratio = 2.11, 95% confidence interval 1.03 to 4.32). The APOE 4 allele may represent an important genetic risk factor for the development of organ damage in homozygous beta-thalassemia.     

Left ventricular diastolic pressure-volume relations in man

Diastolic function of the left ventricle was analysed in patients with different cardiac diseases: acute and chronic volume overload (in aortic and mitral incompetence), pressure overload and inappropriate ventricular hypertrophy (aortic stenosis and hypertrophic cardiomyopathy), congestive cardiomyopathy, and constrictive pericarditis. Most patients were receiving digitalis therapy at the time of study. A constant exponential relation between pressure and volume was assumed, and pressure-volume curves were constructed from two points: the instantaneous pressure-volume relation at beginning-diastole and at end-diastole. The determinants of left ventricular end-diastolic pressure were studied. Left ventricular end-diastolic pressure depended on the beginning-diastolic pressure and volume (O point), the slope of the pressure-volume curve (m), and the volume which distended the ventricle in diastole. In chronic volume loading and in congestive cardiomyopathy the curves were flatter than normal, so that left ventricular end-diastolic pressure was only slightly increased despite the large volume filling the ventricle. In pressure overload and in constrictive pericarditis the curves were steeper than normal. Acute changes in volume were accomplished by a shift up or down the pressure-volume curve but in these patients the slope was not altered: the ventricle had not had time to adapt and end-diastolic pressure was greatly increased.     

A prolonged QRS duration on surface electrocardiogram is a specific indicator of left ventricular dysfunction [see comment

OBJECTIVE: We sought to determine whether a prolonged QRS-interval duration is associated with decreased left ventricular (LV) systolic function. BACKGROUND: The 12-lead electrocardiogram (ECG) is a routine test for suspected cardiac disease. Although several scoring systems have been devised to estimate LV systolic function, no studies have examined the direct relationship between QRS duration alone and LV systolic function. METHODS: We analyzed the standard 12-lead surface ECG of 270 consecutive patients, referred for radionuclide ventriculography. Patients (n = 44) with bundle branch blocks, atrial flutter or fibrillation, pacemaker rhythm, recent myocardial infarction or bypass surgery, and patients on antiarrhythmic drugs were excluded. In the remaining patients (n = 226), we correlated the QRS duration on standard resting ECG, and the resting LV ejection fraction (EF), end-systolic and end-diastolic counts (ESC and EDC, respectively; LV volume indices), as obtained by radionuclide angiography. We used a multivariate analysis to identify independent predictors of reduced ventricular function entering QRS duration, the previously described R-wave score and clinical variables in our model. RESULTS: The QRS duration in the abnormal EF group was significantly longer than in the normal EF group (0.102 vs. 0.091 s, p < 0.0001). A QRS duration >0.10 s was highly specific (83.6%), but modestly sensitive (43.8%), for the prediction of abnormal EF. Furthermore, an abnormal EF was predicted with incrementally increased specificity (83.6% to 99.3%) and a corresponding decrease in sensitivity (43.8% to 13.8%) for each 0.01-s increase in the definition of prolonged QRS (from >0.10 to >0.12 s). Accordingly, the positive likelihood ratio for the prediction of decreased LV function was increased from 2.67 to 19.7 as the definition of prolonged QRS duration was increased from >0.10 to >0.12 s. In the multivariate analysis, a prolonged QRS duration and a low R-wave score were the only independent predictors of decreased LV systolic function. CONCLUSIONS: Prolonged QRS duration (>0.10 s) obtained from a standard resting 12-lead ECG is a specific, but relatively insensitive indicator of decreased LV systolic function. Further prolongation of the QRS had a higher specificity for decreased LV EF and a higher positive likelihood ratio for predicting abnormal LV EF.     

The effect of left ventricular pressure or volume overload on ventricular dimension in children. Left ventricular volume determination from one or two ventricular dimensions

The effect of pressure or volume overload on the geometry of the left ventricle (LV) was determined in order to examine the feasibility and accuracy of LV volume determinations from one minor axis or two dimensions (one minor axis and the longest length). The longest length (LL) and minor axis (MA) in both the anteroposterior (AP) view and lateral (LAT) view were determined from the LV cine silhouette in patients with normal LV volume and pressure (group 1), LV pressure (LVP) overload group (LVP greater than 140 mm Hg, group 2), and LV volume overload group (LV end-diastolic volume greater than 124% of normal, group 3). The ratio of the MA to the LL, which represents the spherical configuration of the LV, was less than "normal" in group 2, and higher than "normal" in group 3. In all groups the LV was less spherical at end-systole than at end-diastole. Additionally, the (MA)3 had a different relationship to true LV volume (biplane LV volume) in the three groups and from diastole to systole in each group. Left ventricular volume calculation from one minor axis was associated with a large error. In contrast, left ventricular volume can be accurately determined from two ventricular dimensions using either the anteroposterior or lateral ventricular image (r larger than or equal to 0.97).