Posterior Wall Thinning Research Articles

Terminal stage cardiac findings in patients with cardiac Fabry disease: An electrocardiographic, echocardiographic, and autopsy study

Fabry disease is caused by deficiency of alpha-galactosidase A, and typically causes multi-organ dysfunction. Patients with manifestations limited to the heart, mainly left ventricular hypertrophy (LVH), have been reported as a disease variation. We have reported a 3% prevalence of this cardiac variant in men with LVH, which we designated 'cardiac Fabry disease'. The purposes of this study were to evaluate the terminal stage cardiac manifestations and autopsy findings in patients with cardiac Fabry disease. We examined seven terminal stage patients with cardiac Fabry disease. During hospitalization, standard 12-lead electrocardiograms, Holter electrocardiograms, and echocardiograms were obtained. Autopsies were performed and macroscopic along with microscopic findings were evaluated. Six patients died of heart failure and one of ventricular fibrillation. Electrocardiograms revealed the presence of conduction abnormalities and nonsustained ventricular tachycardia. Echocardiograms and autopsy findings revealed LVH in all patients. Localized basal posterior wall thinning of the left ventricle was detected in the six patients who died of heart failure. All patients had severe left ventricular dysfunction. Histologically, myocardial cells, but not cardiac vascular endothelial cells, showed glycosphingolipid accumulation. No accumulation was observed in other organs or in systemic vascular endothelial cells. Severe left ventricular dysfunction with associated conduction disturbances and ventricular arrhythmias occur in patients with terminal stage cardiac Fabry disease. Furthermore, LVH is present and associated with thinning of the base of the left ventricular posterior wall. In contrast to typical Fabry disease, accumulation of glycosphingolipids was observed in myocardial cells but not in other organs.

Chronic xanthine oxidase inhibition following myocardial infarction in rabbits: Effects of early versus delayed treatment

Xanthine oxidase (XO) expression is increased in the failing heart, and animal studies in rodents and dogs showed that XO inhibition with allopurinol can improve left ventricular (LV) function and myocardial oxygen efficiency in the failing heart. The purpose of this study was to determine whether chronic XO inhibition by allopurinol or febuxostat, an investigational, potent non-purine, selective inhibitor of XO, could prevent or treat the progression of congestive heart failure (CHF) induced by coronary artery ligation in rabbits, a species that exhibits low intrinsic XO activity similar to humans. One day after coronary ligation, rabbits were assigned to one of four groups ( n = 7–8/group): control group (vehicle for 49 days), early treatment (prevention) group (febuxostat for 49 days), and two delayed-treatment groups (vehicle for 21 days followed by either febuxostat or allopurinol for 28 days). An echocardiogram of the LV was obtained on Days 0 (prior to surgery), 21, and 49. Control rabbits developed CHF by Day 21 (significant reduction in LV shortening fraction and ejection fraction, thinning of the LV posterior wall, and increases in LV internal dimensions and end-diastolic volume). Early preventive treatment with febuxostat significantly lessened the reduction of LV function when compared to vehicle on both Days 21 and 49. These cardiac functional improvements were accompanied by moderately less severe changes in LV dimensional parameters relative to vehicle controls. In contrast, when treatments with XO inhibitors were started after the establishment of CHF, no significant relative improvements in cardiac functional or dimensional parameters were observed. These results suggest that chronic preventive treatment with an XO inhibitor initiated shortly after myocardial infarction can delay or prevent the onset of CHF, and that XO inhibition initiated after establishment of the disease does not offer cardiac protection. In contrast to previous rodent studies which do suggest a cardiovascular (CV) benefit of delayed XO inhibition, the results of this rabbit study are in keeping with those of recently completed studies in severe CHF patients treated with oxypurinol, the active metabolite of allopurinol, in which no clinical benefit was observed. This may be due to the fact that rodents have relatively high levels of XO activity, while the levels in rabbits and humans are intrinsically low, suggesting that the rabbit may be the preferred model for investigating the role of XO in CV diseases.

Long-term Effects of Alcohol Consumption in Male and Female Rats

Discrepancies exist regarding potential sex differences in the effects of ethanol on the myocardium. Therefore, the aims of this study were to determine if long-term ethanol consumption was associated with the development of a dilated cardiomyopathy (CM) in female rats and, second, to determine if the absence of ovarian hormones modulated this effect. Adult male and female (n=6-8/group) sham-operated and ovariectomized (OVX) Sprague-Dawley rats received the Lieber DeCarli ethanol-containing (8% vol/vol) or control liquid diet for 8 months. All ethanol groups showed echocardiographic evidence of a cardiomyopathy; however, more significant ethanol-elicited differences were found in the male ethanol group than in either the female or female OVX groups. In addition, the male ethanol group had significant reductions in in vivo measures of contractility, such as the maximum derivative of change in systolic pressure and preload recruitable stroke work. Sex differences were also apparent in the pattern and degree of posterior and septal wall thickness changes, in that the male ethanol group had more posterior and septal wall thinning. In conclusion, similar to male rats long-term ethanol consumption in gonad-intact and OVX female rats is associated with the development of a dilated cardiomyopathy.

Significance of Asymmetric Basal Posterior Wall Thinning in Patients With Cardiac Fabry’s Disease

Although classic Fabry's disease results in multiple causes of death, the cardiac variant of Fabry's disease affects only the cardiac system and results in initial symmetric left ventricular (LV) hypertrophy and later LV dysfunction, asymmetric basal posterior LV wall thinning, restrictive mitral flow, and functional mitral regurgitation with end-stage chronic heart failure (CHF), leading to death. The purpose of this study was to investigate whether these findings predict prognoses in patients with cardiac Fabry's disease. In 13 consecutive men with cardiac Fabry's disease, LV wall thickness, the ejection fraction, mitral E-wave deceleration time, the LV Tei index, and functional mitral regurgitation were measured by echocardiography. Patients were followed for 5 to 96 months (mean 41 +/- 9). Eight patients developed New York Heart Association class III CHF, and 6 experienced cardiac death. A LV Tei index >0.60 and basal posterior LV wall thinning with a ratio of ventricular septal to posterior wall thickness >1.3 significantly preceded CHF and death (Tei index: 4.4 and 5.1 years; posterior wall thinning: 4.0 and 4.7 years), respectively (p <0.05). In conclusion, an increased LV Tei index and asymmetric basal posterior LV wall thinning are important echocardiographic findings that precede CHF and cardiac death in patients with cardiac Fabry's disease.

Diastolic performance assessed by tissue Doppler after pediatric heart transplantation

Background Diastolic performance, indexed by tissue Doppler imaging (TDI), has been reported to predict cellular rejection in adult heart recipients, but the predictive value of TDI after pediatric heart transplantation is unknown. Methods TDI-derived diastolic performance was studied in 37 pediatric (median age 2.54 years) heart recipients in the absence and presence of rejection. Maximum velocities in diastole of the left ventricular posterior wall thinning (diastvelLVPWmax) and medial mitral valve annulus (MVA) were determined in 160 echocardiograms from recipients who experienced either no rejection (Group 1, n = 22) or ≥1 rejection episode(s) (Group 2, n = 14) during the study interval (2 years). There was 1 death in the immediate post-transplant period not included in the analyses. Results The diastvelLVPWmax determined by TDI in Group 1 increased during the first 90 days post-transplant ( r = 0.31; p = 0.05), was heart-rate-dependent (r = 0.591; p < 0.001), and was significantly lower than the veILVPWmax determined from digitized M-mode tracings (116 ± 31 vs 135 ± 44 mm/s; p < 0.05). In a sub-group of children transplanted during the study and followed for ≥1 year ( n = 9), diastvelLPWmax, determined by TDI, was lower in infant recipients ( n = 6; 106.5 ± 22 mm/s) than in older recipients ( n = 3; 135 ± 36 mm/s; p = 0.015). With rejection, diastvelLVPWmax, determined by M mode (147 ± 13 vs 104 ± 11 mm/s; p < 0.05), was decreased compared with baseline recipient studies prior to rejection. In contrast, rejection did not significantly change diastvelLVPWmax, as determined by TDI. MVA E/A (peak early-to-late diastolic velocity ratio) was significantly decreased with rejection (1.37 ± 0.23 vs 0.92 ± 0.22; p < 0.05). As a single parameter, an MVA E/A <1.1 was predictive of rejection in 4 of 10 recipients with MVA E/A ≥1.1 pre-rejection. Conclusions TDI-derived diastvelLVPWmax varied with age at transplant, heart rate and time post-transplant. A decrease in TDI-derived MVA E/A, but not diastvelLVPWmax, can be of additional predictive value in non-invasive surveillance for rejection in pediatric heart recipients.

Cardiovascular abnormalities with normal blood pressure in tissue kallikrein-deficient mice.

Tissue kallikrein is a serine protease thought to be involved in the generation of bioactive peptide kinins in many organs like the kidneys, colon, salivary glands, pancreas, and blood vessels. Low renal synthesis and urinary excretion of tissue kallikrein have been repeatedly linked to hypertension in animals and humans, but the exact role of the protease in cardiovascular function has not been established largely because of the lack of specific inhibitors. This study demonstrates that mice lacking tissue kallikrein are unable to generate significant levels of kinins in most tissues and develop cardiovascular abnormalities early in adulthood despite normal blood pressure. The heart exhibits septum and posterior wall thinning and a tendency to dilatation resulting in reduced left ventricular mass. Cardiac function estimated in vivo and in vitro is decreased both under basal conditions and in response to beta-adrenergic stimulation. Furthermore, flow-induced vasodilatation is impaired in isolated perfused carotid arteries, which express, like the heart, low levels of the protease. These data show that tissue kallikrein is the main kinin-generating enzyme in vivo and that a functional kallikrein-kinin system is necessary for normal cardiac and arterial function in the mouse. They suggest that the kallikrein-kinin system could be involved in the development or progression of cardiovascular diseases.

The Functional Status of the Cardiovascular System in Children Survivors of Oncological Disease

According to data of Russian Research Institute of Children Oncology and Hematology, the incidence of oncological disease in children is rather high (220 - 240 new cases in Moscow every year). Nevertheless, when started in due time, an adequate treatment results in complete recovery with favorable longterm prognosis in up to 80% of all cases of lymphoblastic leukemia, 95% of lymphogranulomatosis, 65% of lymphosarcoma, 90% of nephroblastoma, and 100% of retinoblastoma. Most children continue to attend general school after recovery. So, examination of functional status of various physiological systems in children survivors of oncological disease is a topical problem. In treating children with oncological disease, it should be taken into account that their growing and developing physiological systems are highly sensitive to various endogenous and exogenous influences [1‐3]. The most important components of complex oncological disease treatment are radiation and chemotherapy. However, their use can be accompanied by unfavorable long-term side-effects associated with lesions in unaffected tissues and organs (dysfunctions in urogenital, endocrine, cardiorespiratory, and/or locomotor systems). It has been shown [4] that 15-year survivors of oncological disease diagnosed during their childhood and treated chemotherapeutically have increased cardiac mortality rates. In this connection, this work was designed to study the functional status of the cardiovascular system in 7- to 17-year-old children and adolescents with long-lasting remissions after cured malignant diseases. All the children examined were in-patients in the rehabilitation department of Research Institute of Children Oncology and Hematology; they continue their schooling according to the standard curricula. Central hemodynamics was examined with echocardiography (EchoCG) and electrocardiography (ECG). The readings were taken with patients resting in the recumbent position. The following EchoCG parameters were recorded: the systolic and diastolic myocardium thickness in the left ventricular posterior wall; enddiastolic and end-systolic left ventricular size and volume; stroke volume; cardiac output; ejection fraction; systolic shortening fraction; systolic speed of the circulatory myocardial fiber shortening; and the blood ejection time. The ECG was recorded with 12 common leads; it was checked for the presence of various disturbances of cardiac rhythm, intraventricular conductance, myocardial recovery, electrical alternation, or decrease in ECG-wave voltage. The volumetric and tonic parameters of cerebral and antebrachial circulation were determined with focused and tetrapolar impedance plethysmography. The study was performed with 75 patients with histories of various malignant diseases (blood malignancies accounted for approximately 70% of cases examined). According to EchoCG data, about 50% of children examined had various myocardial disorders. Frequently (in 50% of cases) there was a 12‐35% decrease in pumping and contractile myocardium capacity. A 12‐20% thinning of the left ventricular posterior wall (relative to the age-specific norm) was found in 20% of children, and was frequently accompanied by the transition zone shift towards the left thoracic leads. Fifteen percent of patients had a 10‐20% widening of the left ventricle expressed on ECG as an abnormal amplitude ratio of R-wave in left V leads. These disorders were combined in 20% of the children. Cardiac arrhythmia, bradycardia, tachycardia, impairments of intraventricular conductance or myocardial recovery, electrical alternation or decrease in ECG-wave voltage were observed in 20, 22, 14, 75, 26, 18, and 10% of the children, respectively. Changes of this complexity in morphofunctional parameters may be regarded as a manifestation of myocardiac dystrophy. Up to 80% of children examined had impairments of peripheral circulation such as the tonic instability of large cerebral and antebrachial vessels or a significant decrease in the tone of small and medium-size antebrachial vessels; in 50% of cases there were restrictions of venous backflow caused by decreased venous tone. These data are characteristic of the high incidence of vascular dystonias in this group of children.

Prognostic value of posterior wall thickness in childhood dilated cardiomyopathy and myocarditis.

M-mode indices of left ventricular dimension and posterior wall thickness were derived from echocardiograms of children presenting with dilated cardiomyopathy/myocarditis and were related to outcome. Echocardiograms from 16 of 18 children were manually digitized to obtain changes of left ventricular dimension and posterior wall thickness throughout the cardiac cycle. Indices of ventricular function and the ratio of end-diastolic posterior wall thickness to cavity dimensions were obtained. Patients were divided into group I (alive, n = 7), and group II (died, n = 6 or heart transplantation, n = 3) at median follow-up of 25 months. No significant difference was seen for the shortening fraction, the percentage of posterior wall thickening or the normalized peak rate of left ventricular filling. The normalized peak rate of posterior wall thinning was greater in group II. The posterior wall thickness to cavity dimension ratio was higher in group I (median = 0.19) than group II (median = 0.13) (P < 0.005). Five of six survivors, whose ventricular function improved, had ratios > 0.17. All but one with a ratio < or = 0.16 remained with a dilated heart, died or required transplantation (P = < 0.01). A relatively thicker posterior wall (ratio > 0.17) was associated with better prognosis and recovery. This index should be taken into account in decision-making regarding timing for cardiac transplantation.

M mode and Doppler echocardiographic assessment of left ventricular diastolic function in primary antiphospholipid syndrome.

High titres of serum antiphospholipid antibodies are a possible pathogenic factor for cardiac lesions in patients with systemic lupus erythematosus. To test the hypothesis of a causal link between high titres of antiphospholipid antibodies in the serum and myocardial involvement in patients without systemic lupus erythematosus. 18 patients with primary antiphospholipid syndrome (recurrent fetal loss, arterial and/or venous thrombosis, high titres of antiphospholipid antibodies, and no criteria for systemic lupus erythematosus) were prospectively studied by cross sectional, M mode, and pulsed Doppler echocardiography, and compared with 18 healthy controls. The pulsed Doppler indices of left ventricular diastolic function included isovolumic relaxation time and four mitral outflow indices: peak velocity of early flow, peak velocity of late flow, early to late peak flow velocity ratio, and rate of deceleration of early flow. Four computerised M mode indices were also measured: peak rate of left ventricular enlargement in diastole, peak rate of posterior wall thinning, peak velocity of lengthening of the posterior wall, and velocity of circumferential chamber lengthening. Compared with controls, patients with primary antiphospholipid syndrome had higher values for isovolumic relaxation time and peak velocity of late mitral outflow and lower values for early to late mitral peak outflow velocity ratio, rate of deceleration of early mitral outflow, peak rate of left ventricular enlargement in diastole, peak rate of posterior wall thinning, peak velocity of lengthening of the posterior wall and velocity of circumferential chamber lengthening. This abnormal pattern reflects an impairment of myocardial relaxation and filling dynamics of the left ventricle in patients with primary antiphospholipid syndrome who were free of any clinically detectable heart disease. These data suggest that high serum titres of antiphospholipid antibodies may be associated with subclinical myocardial damage.

Left ventricular diastolic function in asymptomatic and symptomatic human immunodeficiency virus carriers: an echocardiographic study

Acquired immunodeficiency syndrome (AIDS) is a systemic illness affecting multiple organs, including the heart. Left ventricular (LV) diastolic dysfunction has been reported as the first echocardiographically detectable abnormality in several cardiovascular disorders. We tested the hypothesis that Human Immunodeficiency Virus (HIV) carriers have LV diastolic impairment when studied early in the clinical course of the infection. Doppler echocardiographic and computerized time-motion parameters of LV diastolic function were obtained in 51 HIV patients and in 25 age- and sex-matched healthy controls. The HIV population consisted of 28 totally asymptomatic subjects and 23 patients with incipient AIDS. As compared to controls, the HIV group had similar heart rate, blood pressure level, LV dimensions and fractional shortening, but increased isovolumetric relaxation time (P = 0.03), early filling duration (P < 0.001) and decreased early mitral flow peak velocity (E) (P = 0.02) and EF slope (P < 0.001). HIV patients also showed lower values for posterior wall thinning (PWT, P < 0.01) and peak lengthening velocity of the posterior wall (PVL, P < 0.05), and a trend to a decreased peak rate of LV enlargement in diastole (D+, P = 0.05). Doppler-derived parameters of diastolic function were significantly altered in the asymptomatic HIV group vs controls. The LV diastolic indices were similar in symptomatic and asymptomatic HIV patients except for PWT, which was lower in the symptomatic HIV group (P = 0.04). Since mild and focal wall motion abnormalities were detected in 11 HIV carriers (22%), comparison of LV diastolic indexes between HIV patients and controls was also performed in two subgroups; these included asymptomatic (n = 26) and symptomatic (n = 14) patients with normal contractile state. The two subgroups had abnormalities of diastolic function similar to those of the HIV group as a whole, but with somewhat lower levels of statistical significance. Our data strongly suggest that there is myocardial involvement at the early stage of HIV infection; however, its impact on the clinical course of the disease remains to be clarified.

Effects of a novel inotropic agent (OPC-18790) on systolic and diastolic function in patients with severe heart failure

A double-blind placebo-controlled study to determine the acute hemodynamic and cardiac mechanical effects of the quinolinone derivative OPC-18790 was performed in 12 patients with New York Heart Association class III or IV congestive heart failure. Simultaneous echocardiographic, Doppler, and invasive hemodynamic studies were performed before and after a 6-hour intravenous infusion of drug at 2.5, 5.0, or 10.0 μg/kg/min or of placebo. OPC-18790 (mean dose 5.9 ± 3.5 mg) caused significant increases in left ventricular (LV) ejection fraction (15% ± 4% vs 23% ± 5%; p < 0.05) and cardiac index (1.7 ± 0.4 vs 2.5 ± 0.6 L/min/m 2; p < 0.05) and a rightward and upward shift in the stress-shortening relation. LV end-diastolic volume and heart rate were unchanged. LV filling and posterior LV wall thinning rates from digitized M-mode echocardiographic studies (0.49 ± 0.16 vs 0.75 ± 0.21 cm/sec and 2.0 ± 0.9 vs 3.0 ± 1.4 cm/sec, respectively; both p < 0.05), transmitral deceleration time (67 ± 24 vs 81 ± 19 msec, p < 0.05), and atrial filling fraction (31.0% ± 11.2% vs 38.9% ± 13.9%, p < 0.05), infusion. Despite a significant decrease in pulmonary capillary wedge pressure (28 ± 9 vs 18 ± 10 mm Hg) there was no change in the velocity-time integral of early diastolic filling (53 ± 12 vs 59 ± 22 cm), suggesting improved LV relaxation. Hemodynamics and parameters of LV function were unchanged in the 3 patients receiving placebo. We conclude that in addition to its positive inotropic effects, OPC-18790 may produce hemodynamic benefit by salutary effects on LV relaxation, atrioventricular compliance, and late ventricular diastolic filling.

Effects of intravenous milrinone on left ventricular function in ischemic and idiopathic dilated cardiomyopathy

M-mode echocardiography and Doppler were used to assess the effects of phosphodiesterase inhibition on subendocardial function in dilated cardiomyopathy, and in particular, to study interactions with both systolic and diastolic left ventricular function. Twelve adult patients with dilated cardiomyopathy were studied (6 ischemic in origin and 6 idiopathic), 7 of whom were being considered for cardiac transplantation. Cardiac index increased without significant change in heart rate or blood pressure. Longitudinal mitral ring motion, which had been uniformly reduced, increased markedly after intravenous milrinone. Left ventricular cavity size decreased, and shortening fraction, posterior wall thickness, and rates of posterior wall thickening and thinning increased markedly. Left atrial pressure decreased, and isovolumic relaxation time increased. However, the peak velocity and duration of the transmitral E wave increased, with no change in the A wave. Improved longitudinal (subendocardial) function was reflected by improved posterior wall dynamics, and early filling, possibly by augmentation of restoring forces. Thus, severely reduced subendocardial function in dilated cardiomyopathy is potentially reversible, with marked effects on systolic and diastolic function. These previously unrecognized actions of milrinone provide further evidence to justify its snort-term use in supporting the severely depressed myocardium.

Relation of left ventricular isovolumic relaxation time and incoordination to transmitral Doppler filling patterns.

To investigate factors during isovolumic relaxation that determine Doppler filling patterns in patients with left ventricular disease, and thus to identify the underlying mechanisms. 85 patients (50 ischaemic heart disease, 35 left ventricular hypertrophy due to aortic stenosis) and 26 controls were studied with Doppler and M mode echocardiography and phonocardiography. 16 patients underwent two studies on separate occasions, to find whether changes in isovolumic relaxation time were reflected by a change in the Doppler A/E ratio. A tertiary cardiac referral centre. Patients referred for assessment of coronary artery disease or aortic stenosis with left ventricular hypertrophy. Doppler filling velocities during early (E wave) and late (A wave) diastole and the A/E ratio, acceleration of the E wave, digitised M mode indices of incoordinate relaxation (change in cavity dimension before mitral valve opening and time from minimum dimension to mitral valve opening), isovolumic relaxation time, M mode measures of diastolic function after mitral valve opening (peak rate of posterior wall thinning and peak rate of dimension increase), and left ventricular end diastolic pressure. A/E correlated with age in normal subjects (r = 0.74), to a lesser extent in left ventricular hypertrophy (r = 0.41), but not significantly in ischaemic heart disease. In all patients, isovolumic relaxation time was significantly and negatively correlated with the acceleration of the E wave, showing its fundamental relation to the force responsible for early diastolic filling (r = -0.71 for left ventricular hypertrophy, and -0.74 for ischaemic heart disease, p value < 0.01). In left ventricular hypertrophy and those ischaemic patients without left ventricular dilatation A/E was correlated both with isovolumic relaxation time (r = 0.68 and 0.60 respectively), and with incoordinate relaxation (r = 0.65 and 0.61). In those ischaemic patients with left ventricular dilatation, the influence of incoordination was lost and isovolumic relaxation time became the dominant influence upon A/E (r = 0.82). Weak correlations of end diastolic pressure and RR interval with A/E, became insignificant once isovolumic relaxation time had been taken into account. Isovolumic relaxation time and incoordination together accounted for over 50% of the variance in the A/E ratio in our patients. Isovolumic relaxation time and the A/E ratio were linearly related. Patients with a short isovolumic relaxation time had evidence of considerable diastolic abnormalities, despite a normal Doppler A/E ratio. In the 16 patients who had two echocardiographic studies, changes in the duration of isovolumic relaxation were accompanied by a change in the Doppler A/E ratio. The relation between these two variables, derived from the group as a whole was similar. The main factors influencing the A/E ratio in patients with left ventricular disease are two distinct properties of isovolumic relaxation--namely the duration and the extent of incoordinate wall motion. Filling pressure and RR interval are not significant independent determinants, but act only through an effect upon isovolumic relaxation time. Age is an important influence in normal people, but this effect is attenuated in left ventricular hypertrophy and lost in ischaemic ventricular disease.

Cardiac Function After Surgery for Subaortic Stenosis

OBJECTIVE--To examine left ventricular function after surgical resection of subaortic stenosis during childhood. DESIGN--Left ventricular performance was measured non-invasively in all patients who responded to an invitation for formal assessment. SETTING--Outpatient study, tertiary referral centre. PATIENTS--Twenty three (12 male and 11 female) patients (age range 3 to 31 years) of 43 consecutive patients with fixed subaortic stenosis undergoing surgical resection between 1975 and 1989 reattended for formal assessment 16 months to 15 years (median 4 years 4 months) after operation. MAIN OUTCOME MEASURES--Left ventricular dimension, left ventricular wall thickness, left ventricular Doppler inflow velocities, and left ventricular diastolic pressure (measured from apexcardiograms). Results were compared with those in controls individually matched for age and sex. RESULTS--All patients were symptom free. Left ventricular cavity dimensions were normal, as was the mean fractional shortening. Posterior wall thickness tended to be greater in the patients and there was a significant increase in septal thickness. Normalised peak rate of posterior wall thinning was significantly lower in the patients and the isovolumic relaxation time was significantly shorter. Doppler inflow velocity measurements showed that early diastolic mitral flow acceleration time was normal but deceleration time was significantly shorter in the patients. The ratio of mitral flow in early diastole (E) to E plus mitral flow in late diastole (A) was significantly higher in the patients and in two patients there was complete absence of A wave flow despite large A waves on the apexcardiogram. CONCLUSIONS--Systolic function was well preserved in patients after operation for subaortic stenosis. A restrictive pattern of left ventricular filling was common, however, and presumably reflected a response to the chronic pressure load and to surgery in the paediatric heart.

Cardiac function after surgery for subaortic stenosis: non-invasive assessment of left ventricular performance.

To examine left ventricular function after surgical resection of subaortic stenosis during childhood. Left ventricular performance was measured non-invasively in all patients who responded to an invitation for formal assessment. Outpatient study, tertiary referral centre. Twenty three (12 male and 11 female) patients (age range 3 to 31 years) of 43 consecutive patients with fixed subaortic stenosis undergoing surgical resection between 1975 and 1989 reattended for formal assessment 16 months to 15 years (median 4 years 4 months) after operation. Left ventricular dimension, left ventricular wall thickness, left ventricular Doppler inflow velocities, and left ventricular diastolic pressure (measured from apexcardiograms). Results were compared with those in controls individually matched for age and sex. All patients were symptom free. Left ventricular cavity dimensions were normal, as was the mean fractional shortening. Posterior wall thickness tended to be greater in the patients and there was a significant increase in septal thickness. Normalised peak rate of posterior wall thinning was significantly lower in the patients and the isovolumic relaxation time was significantly shorter. Doppler inflow velocity measurements showed that early diastolic mitral flow acceleration time was normal but deceleration time was significantly shorter in the patients. The ratio of mitral flow in early diastole (E) to E plus mitral flow in late diastole (A) was significantly higher in the patients and in two patients there was complete absence of A wave flow despite large A waves on the apexcardiogram. Systolic function was well preserved in patients after operation for subaortic stenosis. A restrictive pattern of left ventricular filling was common, however, and presumably reflected a response to the chronic pressure load and to surgery in the paediatric heart.

Computerized M-mode echocardiographic assessment of left ventricular diastolic function in patients with familial amyloid polyneuropathy.

To determine left ventricular diastolic properties in patients with familial amyloid polyneuropathy, 23 patients were studied by digitized M-mode echocardiography and were compared with 15 age-matched normal subjects. None of the patients had restrictive ventricular physiology and all but two showed normal left ventricular fractional shortening. Both the normalized peak rate of diastolic increase in left ventricular internal dimension and the normalized peak rate of diastolic thinning of posterior wall were significantly lower in patients than in normal subjects (2.0 +/- 0.8 vs 3.0 +/- 0.4 sec-1; p less than 0.001, and 2.5 +/- 1.2 vs 5.8 +/- 1.0 sec-1; p less than 0.001, respectively). The left ventricular isovolumic relaxation time in patients was 91.5 +/- 22.2 msec, compared with 64.0 +/- 2.6 msec in normal subjects (p less than 0.001). Of the 18 patients without clinical evidence of overt heart disease, 12 had normal ventricular wall thickness and normal fractional shortening, but 10 of the 12 exhibited some abnormalities in diastolic properties. In addition, indexes of diastolic function were significantly related to ventricular wall thickness alone. These findings indicate that left ventricular diastolic abnormalities precede the development of clinically overt heart disease, ventricular wall thickening, and systolic dysfunction and may be related to intramyocardial amyloid infiltration with resultant fibrosis in patients with familial amyloid polyneuropathy.

Impairment of diastolic function by shortened filling period in severe left ventricular disease.

A dilated left ventricle with reduced ejection fraction is usually attributed to impaired systolic function. To investigate the possibility that ventricular filling might also be disturbed, M mode echocardiograms, phonocardiograms, and Doppler cardiograms were recorded in 30 patients with ventricular disease of varying cause. All but four had functional mitral regurgitation. The size of the left ventricular cavity was increased in all and peak velocity of circumferential fibre shortening was reduced. Diastolic abnormalities included a short isovolumic relaxation time, and, on digitised M mode, a reduced rate of dimension increase and of posterior wall thinning. Although the timing of aortic valve closure was normal, mitral regurgitation persisted beyond it by 95 (35) ms and beyond mitral valve opening by 60 (40) ms. This reduced the effective filling time (the interval when the mitral valve was open and mitral regurgitation was absent) to less than 200 ms in seven patients. The effective filling time correlated closely with the RR interval, the regression equation indicating a reduction of 80 ms for each 100 ms fall in RR interval. It was also independently shortened by 2 ms a year with increasing age. The effective left ventricular filling time may thus be very short in patients with left ventricular cavity dilatation and functional mitral regurgitation. It is suggested that when diastolic function is also abnormal, this short filling time may physically limit ventricular inflow. Its close relation to heart rate might contribute to the therapeutic effect of beta blockade in such patients.

Phase differences between left ventricular wall motion and transmitral flow in man: evidence for involvement of ventricular restoring forces in normal rapid filling

To assess the possible role of restoring forces underlying left ventricular wall motion during rapid filling, the time relations between left ventricular dimensions and filling velocity were studied by digitised M-mode and Doppler echocardiography in 23 normal children and 43 patients: 11 with mild and 17 with severe mitral regurgitation, and 15 with left ventricular hypertrophy due to aortic stenosis. In normal children, peak mitral flow velocity characteristically lagged peak rate of dimension increase by 50 ± 15 msec, and peak rate of posterior wall thinning by 35 ± 15 msec, ( P < 0.01 for both). Towards the apex, and along the long axis of the ventricle, these phase differences between dimension and flow velocity were not apparent. The characteristic time relations between flow velocity and transverse dimension were also present in patients with left ventricular hypertrophy or mild mitral regurgitation, but when mitral regurgitation was severe they were lost and there was no significant difference in timing between peak flow velocity and peak rate of dimension change (−2 ± 30 msec) or wall thinning (−4 ± 25 msec). We conclude that phase differences between left ventricular wall motion and mitral inflow velocity are present in the normal ventricles of children. They cannot be explained on the basis of simple shape changes or passive filling of the relaxing ventricle, but strongly suggest the additional presence of ventricular restoring forces. They persist in patients with left ventricular hypertrophy or mild mitral regurgitation, but are lost when the regurgitation is severe, the filling pattern reverting to that predicted for passive distension of the ventricular cavity by a high left atrial pressure.

Regional Relaxation Abnormalities in Coronary Artery Disease

Global left ventricular diastolic dysfunction may be detected in chronic coronary artery disease patients with normal systolic function. M-mode echocardiography was used to investigate the regional left ventricular wall thickening/thinning dynamics that might be responsible for abnormal left ventricular filling in patients with normal or mildly decreased left ventricular ejection fraction. Regional thinning was evaluated in 22 patients with coronary artery disease; comparison regional thickening and thinning indices were derived from 8 angiographically normal control subjects. Regional peak left ventricular posterior wall thinning and early fractional filling decreased from 99 to 65.3 mm/s and from 0.73 to 0.65, respectively, in segments with decreased thickening. By contrast, in posterior wall segments with normal contractility, peak thinning and early fractional filling remained unchanged at 98.2 mm/s and 0.71, respectively. During atrial systole, the peak rate of posterior wall thinning increased in normal and decreased thickening segments from 30.2 to 47.2 and to 44.2 mm/s, respectively. The increase in fractional thinning with atrial systole was only significant, however, in areas with decreased thickening (from 0.15 to 0.25). Thus, in coronary disease patients the results show: (1) areas with decreased systolic function may show disproportionate diastolic dysfunction; (2) ‘compensatory’ early diastolic changes in wall thinning are not demonstrated by areas with normal systolic function, and (3) atrial systole assumes increased importance in maintaining left ventricular diastolic function. These findings suggest that the mechanism for the increased sensitivity of measures of global diastolic function for detecting coronary artery disease may result from a decrease in early relaxation in segments with systolic dysfunction and an inadequate compensatory hyperrelaxation of segments with normal systolic function. Active atrial contraction becomes a major compensatory mechanism for maintaining ventricular filling with diastolic dysfunction.

Impaired Left Ventricular Diastolic Function in Athletes After Utterly Strenuous Prolonged Exercise

Digitized M mode echocardiography was used to evaluate the effect of a competitive 24-h run on the left ventricular diastolic function in 12 well-trained marathon runners who completed 146-227 km during the race. Mitral valve opening was delayed, early diastolic filling was decreased and prolonged, and posterior wall thinning was reduced, particularly among those athletes completing close to 200 km or more. Since the alterations were in part the opposite in those running 160 km or less, only the reductions in the peak rate of dimension increase (P less than 0.05) and posterior wall thinning (P less than 0.01) were significant in the group as a whole. The delay in mitral valve opening (r = 0.76), the decrease in the peak rate of dimension increase (r = -0.68), and the prolongation of the early diastolic filling period (r = 0.60) were correlated with the distance completed. The reductions in left ventricular end-diastolic dimension and fractional shortening were not in proportion to the distance run, however (r = 0.23 and 0.46, respectively). Measurements made on six athletes 2-3 days after the race showed reversal of the indices of left ventricular diastolic function. Extremely exhaustive prolonged exercise thus appears to result in a marked reversible impairment in left ventricular relaxation and filling. Since the effect of these abnormalities in cardiac filling during exercise is probably more important due to the shorter diastole, the prevention of hypohydration, which could otherwise further compromise left ventricular filling, becomes crucial.