Left atrial and left ventricular diastolic function during acute myocardial ischaemia

Objective—To study indices of diastolic left ventricular function during the first few seconds of myocardial ischaemia.Design—Isovolumic and total relaxation times and left atrial and left ventricular dP/dt were identified from high fidelity (micromanometer) pressure recordings in the left ventricle and left atrium during percutaneous transluminal angioplasty of the left anterior descending coronary artery.Patients—20 patients with isolated disease of the left anterior descending artery and normal left ventricular function.Results—The isovolumic relaxation time lengthened during the first seven to nine seconds of ischaemia; then it shortened by an average of 15% up to the twentieth second, initially as a result of increased left atrial contractility and subsequently because of impaired ventricular relaxation. Ventricular ischaemia resulted in impaired left ventricular diastolic compliance, as shown by an increase in the total relaxation time, before there was evidence of systolic impairment. Minimum dP/dt decreased progressively (by −37% at the twentieth second of ischaemia), whereas maximum dP/dt fell only after 20 seconds of ischaemia (by −11%).Conclusions—Relaxation and filling of the left ventricle (indices of diastolic function) are more sensitive to myocardial ischaemia than myocardial contractility and systolic function. Left atrial contractility increases during left ventricular ischaemia.     

Left atrial and left ventricular diastolic function during acute myocardial ischaemia.

OBJECTIVE--To study indices of diastolic left ventricular function during the first few seconds of myocardial ischaemia. DESIGN--Isovolumic and total relaxation times and left atrial and left ventricular dP/dt were identified from high fidelity (micromanometer) pressure recordings in the left ventricle and left atrium during percutaneous transluminal angioplasty of the left anterior descending coronary artery. PATIENTS--20 patients with isolated disease of the left anterior descending artery and normal left ventricular function. RESULTS--The isovolumic relaxation time lengthened during the first seven to nine seconds of ischaemia; then it shortened by an average of 15% up to the twentieth second, initially as a result of increased left atrial contractility and subsequently because of impaired ventricular relaxation. Ventricular ischaemia resulted in impaired left ventricular diastolic compliance, as shown by an increase in the total relaxation time, before there was evidence of systolic impairment. Minimum dP/dt decreased progressively (by -37% at the twentieth second of ischaemia), whereas maximum dP/dt fell only after 20 seconds of ischaemia (by -11%). CONCLUSIONS--Relaxation and filling of the left ventricle (indices of diastolic function) are more sensitive to myocardial ischaemia than myocardial contractility and systolic function. Left atrial contractility increases during left ventricular ischaemia.     

Effects of abnormal activation on the time course of the left ventricular pressure pulse in dilated cardiomyopathy

Objective—To investigate the effects of QRS duration on characteristics of the left ventricular pressure pulse derived from the time course of functional mitral regurgitation by continuous wave Doppler.

Design—Retrospective and prospective study of 50 patients with dilated cardiomyopathy, by electrocardiography, echocardiography, and Doppler cardiography.

Setting—Tertiary cardiac referral centre.

Patients—50 patients (mean age (SD) 58 (16)) with dilated cardiomyopathy, all with functional mitral regurgitation.

Results—The values of QRS duration ranged widely, from 70 to 190 ms with a mean value of 110 ms, and were unimodally distributed. The overall duration of mitral regurgitation correlated positively with QRS time (r=0·65) over the entire range of values. When the duration of mitral regurgitation was divided into contraction, aortic ejection, and relaxation times, increased QRS duration prolonged contraction (r=0·51) and relaxation (r=0·52) times. Aortic ejection time was affected by RR interval (r=0·74). Duration of QRS correlated negatively with peak rate of rise in left ventricular pressure (+dP/dt) (r=−0·48), and positively with the time intervals from Q to peak pressure (r=0·49) and to peak +dP/dt (r=0·72), and also with those from the start of mitral regurgitation to peak pressure (r=0·49) and to peak +dP/dt (r=0·76). Duration of QRS did not directly affect the peak rate of left ventricular pressure fall (−dP/dt), or the isovolumic relaxation period.

Conclusions—Values of QRS duration are unimodally distributed in patients with dilated cardiomyopathy, without evidence of a discrete group of patients with left bundle branch block. Prolonged QRS duration reduces peak +dP/dt, prolongs overall duration of the pressure pulse, the time to peak +dP/dt, and relaxation time. Duration of QRS must therefore be taken into account in assessing standard measurements of myocardial function in patients with dilated cardiomyopathy.

     

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

Objective—To investigate factors during isovolumic relaxation that determine Doppler filling patterns in patients with left ventricular disease, and thus to identify the underlying mechanisms.

Design—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.

Setting—A tertiary cardiac referral centre.

Subjects—Patients referred for assessment of coronary artery disease or aorticstenosis with left ventricular hypertrophy.

Main outcomes measures—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.

Results—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.

Conclusions—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.

     

Effect of levosimendan on myocardial contractility, coronary and peripheral blood flow, and arrhythmias during coronary artery ligation and reperfusion in the in vivo pig model

OBJECTIVE—To determine whether levosimendan, a calcium sensitiser that facilitates the activation of the contractile apparatus by calcium, improves myocardial contractile function during severe ischaemia and reperfusion without exacerbating the incidence of arrhythmias.
DESIGN—Pigs were pretreated orally twice daily for 10 days with 0.08 mg/kg levosimendan or placebo. On day 11 the left main coronary artery was ligated for 30 minutes, followed by 30 minutes of reperfusion. A bolus dose of levosimendan, 11.2 µg/kg intravenously, or placebo was given 30 minutes before coronary ligation, followed by a continuous infusion of 0.2 µg/kg/min levosimendan or placebo for the remainder of the experiment.
RESULTS—During the ischaemic period, cardiac output was higher in the levosimendan group than in the placebo group (mean (SD): 2.6 (0.5) v 2.0 (0.2) l/min, p < 0.05) and systemic vascular resistance was lower (2024 (188) v 2669 (424) dyne.s⁻¹.cm⁻⁵, p < 0.005). During reperfusion, cardiac output and contractility (LV_maxdP/dt (pos), 956 (118) v 784 (130) mm Hg/s, p < 0.05) were increased by levosimendan. The incidence of ischaemic ventricular fibrillation and tachycardia was similar in the two groups but there were more arrhythmic events (ventricular tachycardia and ventricular fibrillation) in the levosimendan treated group (8/12 levosimendan v 1/9 control p = 0.05).
CONCLUSIONS—Levosimendan improved cardiac output and myocardial contractility during coronary artery ligation and reperfusion. However, it increased the number of arrhythmic events during ischaemia in this model of in vivo regional ischaemia.


Keywords: calcium sensitisers; myocardial ischaemia; arrhythmias     

Effects of abnormal activation on the time course of the left ventricular pressure pulse in dilated cardiomyopathy

Objective—To investigate the effects of QRS duration on characteristics of the left ventricular pressure pulse derived from the time course of functional mitral regurgitation by continuous wave Doppler.Design—Retrospective and prospective study of 50 patients with dilated cardiomyopathy, by electrocardiography, echocardiography, and Doppler cardiography.Setting—Tertiary cardiac referral centre.Patients—50 patients (mean age (SD) 58 (16)) with dilated cardiomyopathy, all with functional mitral regurgitation.Results—The values of QRS duration ranged widely, from 70 to 190 ms with a mean value of 110 ms, and were unimodally distributed. The overall duration of mitral regurgitation correlated positively with QRS time (r=0·65) over the entire range of values. When the duration of mitral regurgitation was divided into contraction, aortic ejection, and relaxation times, increased QRS duration prolonged contraction (r=0·51) and relaxation (r=0·52) times. Aortic ejection time was affected by RR interval (r=0·74). Duration of QRS correlated negatively with peak rate of rise in left ventricular pressure (+dP/dt) (r=−0·48), and positively with the time intervals from Q to peak pressure (r=0·49) and to peak +dP/dt (r=0·72), and also with those from the start of mitral regurgitation to peak pressure (r=0·49) and to peak +dP/dt (r=0·76). Duration of QRS did not directly affect the peak rate of left ventricular pressure fall (−dP/dt), or the isovolumic relaxation period.Conclusions—Values of QRS duration are unimodally distributed in patients with dilated cardiomyopathy, without evidence of a discrete group of patients with left bundle branch block. Prolonged QRS duration reduces peak +dP/dt, prolongs overall duration of the pressure pulse, the time to peak +dP/dt, and relaxation time. Duration of QRS must therefore be taken into account in assessing standard measurements of myocardial function in patients with dilated cardiomyopathy.     

Left ventricular filling characteristics in pulmonary hypertension: a new mode of ventricular interaction

Objective—To examine the effects of pulmonary hypertension on left ventricular diastolic function and to relate the findings to possible mechanisms of interdependence between the right and left sides of the heart in ventricular disease.

Design—A retrospective and prospective analysis of echocardiographic and Doppler studies.

Setting—A tertiary referral centre for both cardiac and pulmonary disease.

Patients—29 patients with pulmonary hypertension (12 primary pulmonary hypertension, 10 pulmonary fibrosis, five atrial septal defect (ASD), and two scleroderma) were compared with a control group of 10 patients with an enlarged right ventricle but normal pulmonary artery pressure (six ASD, one after ASD closure, one ASD and pulmonary valvotomy, one tricuspid valve endocarditis and repair, and one pulmonary fibrosis). None had clinical or echocardiographic evidence of intrinsic left ventricular disease.

Main Outcome measures—M mode echocardiographic measurements were made of septal thickness, and left and right ventricular internal cavity dimensions. Doppler derived right ventricular to right atrial pressure drop, and time intervals were measured, as were isovolumic relaxation time, and Doppler left ventricular filling characteristics.

Results—The peak right ventricular to right atrial pressure gradient was (mean (SD)) 60 (16) mm Hg in pulmonary hypertensive patients, and 18 (5) mm Hg in controls. The time intervals P₂ to the end of the tricuspid regurgitation, and P₂ to the start of tricuspid flow were both prolonged in patients with pulmonary hypertension compared with controls (115 (60) and 120 (40) ν 40 (15) and 45 (10) ms, p values <0·001). Pulmonary hypertensive patients commonly had a dominant A wave on the transmitral Doppler (23/29); however, all the controls had a dominant E wave. Isovolumic relaxation time of the left ventricle was prolonged in pulmonary hypertensive patients compared with controls, measured as both A₂ to mitral valve opening (80 (25) ν 50 (15) ms) and as A₂ to the start of mitral flow (105 (30) ν 60 (15) ms, p values <0·001). The delay from mitral valve opening to the start of transmitral flow was longer in patients with pulmonary hypertension (30 (15) ms) compared with controls (10 (10) ms, p < 0·001). At the time of mitral opening there was a right ventricular to right atrial gradient of 12 (10) mm Hg in pulmonary hypertensive patients, but this was negligible in controls (0·4 (0·3) mm Hg, p < 0·001).

Conclusions—Prolonged decline of right ventricular tension, the direct result of severe pulmonary hypertension, may appear as prolonged tricuspid regurgitation. It persists until after mitral valve opening on the left side of the heart, where events during isovolumic relaxation are disorganised, and subsequent filling is impaired. These effects are likely to be mediated through the interventricular septum, and this right-left ventricular asynchrony may represent a hitherto unrecognised mode of ventricular interaction.

     

Left ventricular beat to beat performance in atrial fibrillation: dependence on contractility, preload, and afterload

OBJECTIVE—To assess independent determinants of beat to beat variation in left ventricular performance during atrial fibrillation.
DESIGN—Prospective study.
SETTING—University hospital.
PATIENTS—Seven patients with chronic non-valvar atrial fibrillation.
INTERVENTIONS—Invasive and non-invasive haemodynamic variables were assessed using a non-imaging computerised nuclear probe, a balloon tipped flow directed catheter, and a non-invasive fingertip blood pressure measurement system linked to a personal computer.
MAIN OUTCOME MEASURES—Left ventricular ejection fraction, left ventricular volume, ventricular cycle length, pulmonary capillary wedge pressure, and measures of left ventricular afterload (end systolic pressure/stroke volume) and contractility (end systolic pressure/end systolic volume) were calculated on a beat to beat basis during 500 consecutive RR intervals. A statistical model of the beat to beat variation of the ejection fraction containing these variables was constructed by multiple regression analysis.
RESULTS—Positive independent relations with ejection fraction were found for preceding RR interval, contractility, and end diastolic volume, while inverse relations were found for afterload, preceding end systolic volume, and preceding contractility (all variables, p < 0.0001). A relatively strong interaction was found between end diastolic volume and afterload, indicating that ejection fraction was relatively more enhanced by preload in the presence of low afterload.
CONCLUSIONS—The varying left ventricular systolic performance during atrial fibrillation is independently influenced by beat to beat variation in cycle length, preload, afterload, and contractility. Beat to beat variation in preload shows its effect on ventricular performance mainly in the presence of a low afterload.


Keywords: atrial fibrillation; contractility; haemodynamic variables     

Streptokinase induced defibrination assessed by thrombin time: effects on residual coronary stenosis and left ventricular ejection fraction

Objective—To evaluate laboratory markers of defibrination early after thrombolytic therapy and to determine their relation to residual stenosis and left ventricular ejection fraction measured angiographically before discharge from hospital.

Design—Prospective analysis of defibrination after streptokinase measured by fibrinogen assay and thrombin time to provide a comparison of these coagulation variables for predicting angiographic responses to treatment in patients with acute myocardial infarction.

Setting—The coronary care unit of a district general hospital.

Patients—44 patients with acute myocardial infarction treated by streptokinase infusion, all of whom underwent paired blood sampling before and one hour after streptokinase and cardiac catheterisation at a median of six (interquartile range 3–9) days later.

Main outcome measures—Assay of thrombin time and plasma fibrinogen concentrations one hour after streptokinase infusion. Relations between these coagulation variables and residual stenosis in the infarct related coronary artery and left ventricular ejection fraction. Separate analyses are presented for all patients (n = 44) and those with patency of the infarct related artery (n = 35).

Results—Streptokinase infusion produced profound defibrination in every patient as shown by changes in thrombin time and circulating fibrinogen. Thrombin time after streptokinase infusion correlated significantly with both residual stenosis (r = −0·43, p < 0·005) and left ventricular ejection fraction (r = 0·38, p < 0·02). The importance of these correlations was emphasised by the interquartile group comparison which showed that a thrombin time ≥49 seconds predicted a residual stenosis of 74% and an ejection fraction of 65%, compared with 90% and 49% for a thrombin time ≤31 seconds (p < 0·01). When the analysis was restricted to patients with patency of the infarct related artery, the correlation between thrombin time and residual stenosis remained significant and group comparisons continued to show that patients in the highest quartile range had more widely patent arteries and better preservation of ejection fraction. Analysis of the fibrinogen data, on the other hand, showed insignificant or only marginally significant correlations with these angiographic variables.

Conclusions—Early after streptokinase infusion for acute myocardial infarction, the level of defibrination measured by thrombin time has an important influence on residual coronary stenosis and left ventricular ejection fraction at discharge from hospital, values above 49 seconds being associated with the best angiographic result.

     

Early vasodilator treatment in myocardial infarction: appropriate for the majority or minority?

Objective—To assess the influence of vasodilator treatment started early after myocardial infarction on left ventricular size and function.

Setting—Coronary care unit, Royal Infirmary, Edinburgh.

Patients—105 patients with acute myocardial infarction (systolic blood pressure >90 mm Hg) were randomised within 24 hours of the start of pain. Unlike previous studies 88% of the patients received thrombolysis.

Methods—Double blind randomised placebo controlled study with either 12·5 mg of captopril three times daily or 20 mg of isosorbide mononitrate three times daily for 28 days.

Main outcome measures—Clinical outcome and left ventricular size and function assessed by echocardiography, radionuclide ventriculography, and magnetic resonance imaging.

Results—There was no difference in left ventricular size or function in either treatment group as measured one week after the end of the trial. Even the placebo group tended to decrease left ventricular diameter over the four week study period (one week: 5·0 (0·1) ν, five weeks: 4·8 (0·1) cm, NS). Four patients had an adverse clinical outcome in the placebo group whereas no adverse outcome was seen in the captopril group.

Conclusions—Vasodilator treatment may be of limited value or of no benefit for most infarct patients, particularly those treated with thrombolytic agents. Captopril, however, may benefit patients at high risk.

     

Myocardial dysfunction in patients infected with HIV: prevalence and risk factors

Objectives—To determine the prevalence of and risk factors for myocardial dysfunction in HIV infection.

Subjects—173 patients infected with HIV underwent echocardiography. 119 were current or previous injection drug users, 38 were homosexuals, 10 were haemophiliac patients, and six were heterosexual.

Main outcome measure—Detection of impaired ventricular function.

Results—26 patients with abnormalities of ventricular size or function or both were identified. The abnormality was (a) dilated cardiomyopathy in 13 patients (eight homosexuals, three drug users, and two haemophiliacs) with a mean CD4 count of 38 cells/mm³, which accords with end-stage disease (in addition, three patients were identified as having borderline impairment of left ventricular function); (b) left ventricular dilatation without loss of function in a further six patients; and (c) isolated right ventricular dilation in seven patients. Follow up echocardiograms were obtained in 71 patients, 18 of whom had myocardial dysfunction (103 echocardiograms, mean (SD) 2·5 (0·6) scans per patient, mean interval 200 (116) days, range 14–538 days). These showed that in four cases of isolated right ventricular dilatation, one of isolated left ventricular dilatation, and two with borderline left ventricular dysfunction myocardial function subsequently reverted to normal. There was no excess of exposure to zidovudine in the patients with myocardial dysfunction. Similarly, patients with myocardial dysfunction had no serological evidence of excess secondary infection with Toxoplasma gondii and cytomegalovirus.

Conclusions—There was a high prevalence and wide range of myocardial dysfunction in HIV positive patients. Dilated cardiomyopathy was a feature of advanced HIV disease and affected all major risk groups for HIV infection. In contrast, isolated dilatation of either ventricle occurred at an earlier stage of HIV infection and, particularly in the case of the right ventricle, often was transient. Neither treatment with zidovudine nor infection with Toxoplasma gondii or cytomegalovirus seemed to be responsible for these findings.

     

Subclinical cardiomyopathy in Becker muscular dystrophy

Objective—To investigate the prevalence, age distribution, and spectrum of cardiac involvement in a cohort of patients with Becker muscular dystrophy.

Design—A prospective non-invasive study with clinical, electrocardiographic, and echocardiographic assessment.

Patients—19 patients (age range 16–41 years) with Becker muscular dystrophy attending the Muscle Clinic at Hammersmith Hospital and 22 healthy controls (age range 22–36 years).

Results—17 patients (89%) were symptom free; two had exertional dyspnoea. Three had a past history of acute pericarditis. The electrocardiogram was abnormal in 14 patients (74%). Intraventricular conduction delay or right bundle branch block was present in eight (42%). Three (16%) had tall R waves (R/S > 1) in lead V1 in the absence of right bundle branch block and eight (42%) had Q waves in the lateral and inferolateral leads. The PQ interval was significantly shorter in patients with Becker muscular dystrophy (p < 0·01). Echocardiography showed left ventricular dilatation in seven patients (37%) and 12 (63%) had subnormal systolic function caused by global hypokinesia (fractional shortening <27%). Six of these patients were under the age of 22 years. Patients with Becker muscular dystrophy had significant reduction of both fractional shortening and corrected mean velocity of circumferential shortening compared with controls. No correlation was found between fractional shortening and age.

The third filling fraction was significantly reduced in patients with Becker muscular dystrophy (p < 0·05), although other indices of diastolic function (isovolumic relaxation time and E/A ratios) were not significantly different.

Conclusions—Though most patients with Becker muscular dystrophy were symptom free, a high percentage had evidence of a subclinical cardiomyopathy. Electrocardiography showed that the inferolateral and posterior segments of the left ventricle tended to be affected and may show evidence for conduction tissue disease. Echocardiography showed that most patients had left ventricular dilation and global hypokinesia. The severity of left ventricular disease was unrelated to age; some younger patients had severe left ventricular dysfunction. All patients with Becker muscular dystrophy should have echocardiographic assessment of left ventricular function.

     

Usefulness of Doppler echocardiographic assessment of diastolic filling in distinguishing “athlete''s heart” from hypertrophic cardiomyopathy

Objective—In some athletes with a substantial increase in left ventricular wall thickness, it may be difficult to distinguish with certainty physiological hypertrophy due to athletic training from hypertrophic cardiomyopathy. The purpose of the present investigation was to determine whether assessment of left ventricular filling could differentiate between these two conditions.

Design—Doppler echocardiography was used to obtain transmitral flow velocity waveforms from which indices of left ventricular diastolic filling were measured. Normal values were from 35 previously studied control subjects.

Setting—Athletes were selected mostly from the Institute of Sports Science (Rome, Italy), and patients with hypertrophic cardiomyopathy were studied at the National Institutes of Health (Bethesda, Maryland).

Participants—The athlete group comprised 16 young competitive athletes with an increase in left ventricular wall thickness (range 13–16 mm; mean 14). For comparison, 12 symptom free patients with non-obstructive hypertrophic cardiomyopathy were selected because their ages and degree of hypertrophy were similar to those of the athletes.

Results—In the athlete group, values for deceleration of flow velocity in early diastole, peak early and late diastolic flow velocities, and their ratio were not significantly different from those obtained in untrained normal subjects; furthermore, Doppler diastolic indices were normal in each of the 16 athletes. Conversely, in patients with hypertrophic cardiomyopathy, mean values for Doppler diastolic indices were significantly different from both normal subjects and athletics (p = 0·01 to 0·003), and one or more indices were abnormal in 10 (83%) of the 12 patients.

Conclusions—Doppler echocardiographic indices of left ventricular filling may aid in distinguishing between pronounced physiological hypertrophy due to athletic training and pathological hypertrophy associated with hypertrophic cardiomyopathy.

     

Ventricular mass and diastolic function in patients infected by the human immunodeficiency virus

OBJECTIVE—Echocardiographic and Doppler analysis of myocardial mass and diastolic function in patients infected with HIV.
DESIGN—Case-control study.
SETTING—Tertiary referral centre, Huelva, Spain.
PATIENTS—61 asymptomatic patients with HIV infection and 32 healthy controls.
MAIN OUTCOME MEASURES—Time motion, cross sectional, and Doppler echocardiographic studies were performed, and left ventricular mass and diastolic function variables determined (peak velocity of early and late mitral outflow and isovolumic relaxation time).
RESULTS—Left ventricular mass index (LVMI) was decreased in patients compared with healthy controls (mean (SD): 76.7 (23.6) v 118.8 (23.5) g/m², p < 0.001). Linear regression analysis showed a correlation between LVMI and brachial fat and muscle areas. The ratio of peak velocities of early and late mitral outflow was decreased in HIV infected patients compared with controls (1.19 (0.44) v 1.58 (0.38), p < 0.001). This ratio was exclusively related to haemodynamic variables (heart rate, systolic and diastolic blood pressures). HIV infected patients had a prolonged isovolumic relaxation time (103.0 (10.5) v 72.9 (12.9) ms, p < 0.001). Isovolumic relaxation time was correlated only with brachial muscle area on multivariate analysis.
CONCLUSIONS—HIV infected patients had a reduced left ventricular mass index and diastolic functional abnormalities. These cardiac abnormalities are predominantly related to nutritional status.


Keywords: HIV infection; cardiac function; nutrition     

Increased circulating atrial natriuretic factor concentrations in patients with chronic heart failure after inhibition of neutral endopeptidase: effects on diastolic function

Objective—±Candoxatrilat was used to raise atrial natriuretic factor (ANF) concentrations in patients with heart failure, and the effects on left ventricular systolic and diastolic function were studied to determine the contribution of peripheral and central mechanisms to the haemodynamic effects.     

Myocardial relaxation in atrial fibrillation

Although myocardial contractility has been known to vary from beat to beat in atrial fibrillation, myocardial relaxation in this arrhythmia has not been investigated. In this study, left ventricular relaxation was examined in seven patients with atrial fibrillation (four with mitral valve disease, one with aortic regurgitation, one with secundum type atrial septal defect and one with apical left ventricular hypertrophy). The left ventricular pressure was measured with a micromanometer-tipped catheter and the time constant of isovolumic left ventricular pressure decline (the relaxation time constant) was calculated by means of exponential curve fitting from more than 20 consecutive beats in each patient. The maximal rate of rise of left ventricular pressure (dP/dt) and the relaxation time constant were examined in relation to the preceding RR interval (RR2) and to the ratio of the RR2 interval to the pre-preceding RR interval (RR2/RR1), and the correlation coefficients were obtained. The dP/dt correlated better with RR2/RR1 than with the RR2 interval (0.82 +/- 0.05 versus 0.48 +/- 0.2), but the relaxation time constant did not show any correlation with RR2/RR1 or the RR2 interval (0.03 +/- 0.21 and 0.06 +/- 0.21, respectively). The relaxation time constant was fairly constant in each patient even when the RR2 interval and RR2/RR1 varied greatly. Thus, relaxation in atrial fibrillation is independent of changes in contractility as seen in the relation between postextrasystolic relaxation and postextrasystolic potentiation of contractility.     

Vasodilator myocardial perfusion imaging: demonstration of local electrophysiological changes of ischaemia

Objective—To examine the incidence and severity of myocardial ischaemia provoked in the course of perfusion scintigraphy by coronary vasodilators using endocardial recordings of steady state monophasic action potentials as an independent marker of early localised myocardial ischaemia.

Patients—31 men undergoing routine cardiac catheterisation for investigation of chest pain were studied.

Setting—A tertiary cardiac referral centre.

Design—Single site monophasic action potentials were recorded from the left or right ventricle or both (50 recording sites) during intravenous infusion of dipyridamole (0·015 mg/kg/min) for four minutes. Heart rate was held constant with atrial pacing at 20% above the patient's resting rate. Technetium-99m hexakis-2-methoxy-2-methylpropyl-isonitrile (MIBI) was administered four minutes after dipyridamole, and single photon emission tomographic imaging was performed an hour later. Rest images were obtained the next day (two day, two dose protocol). Recordings were divided into three groups based on the scintigraphic perfusion characteristics and coronary anatomical data for the action potential recording site: group 1—recordings from areas with a normal perfusion pattern (n = 30), group 2—recordings from areas with a perfusion defect and subtended by significantly narrowed coronary arteries without obvious angiographic collateral supply (n = 10), and group 3—recordings from areas with a perfusion defect and subtended by occluded arteries with angiographically evident collaterals from adjacent vessels (n = 10).

Results—There were changes in the duration of the monophasic action potential indicative of ischaemia—that is, shortening of duration of steady state action potential—in 18 of the 20 recordings from areas of abnormal perfusion. Peak changes were apparent eight minutes from the start of the dipyridamole infusion. Mean (SEM) values for duration of the action potential between control and peak effect at eight minutes were 276·5 (5·3) ms ν 276·6 (5·4) for group 1 (NS), 289·6 (4·7) ms ν 278·4 (4·9) ms for group 2 (p < 0·001), and 269·6 (5·7) ms ν 242·0 (4·4) for group 3 (p < 0·0001). These changes were significantly different between the three groups (p < 0·01). ST segment changes on the surface electrocardiogram were seen in only eight patients, all with areas of viable myocardium supplied by collateral vessels.

Conclusions—These data provide strong evidence for the presence of myocardial ischaemia in regions of reversible perfusion defects induced by dipyridamole. This study also shows that such ischaemia is more intense and more likely to be seen when myocardial viability is dependent on collateral circulation.

     

Contractile and relaxation reserve of the left ventricle. II. Patients with rheumatic valvular disease (author's transl)

The function of the left ventricle is important for the success of surgery. To differentiate between normal and abnormal ventricular function, the contractile and relaxation reserve was measured. In 19 patients, 10 with mitral and 9 with aortic valve disease, max dP/dt and min dP/dt were measured at rest and during exercise (ergometer). Max dP/dt increased in 7 patients above 3200 mm Hg/s and dP/dt/P above 60 s-1 (normal contractile reserve). Only 3 of these patients reached a normal increment of relaxation velocity (min dP/dt above 2400 mm Hg/s). In 12 patients the contractile and relaxation reserve was decreased. All patients with mitral stenosis had abnormal relaxation reserve despite normal contractile function in 4 cases. Left ventricular enddiastolic pressure did not correlate well with myocardial dysfunction. Isovolumic contractility during exercise was decreased in patients with aortic valve disease. Enddiastolic pressure increased from 18 +- 8 to 22 +- 14 mm Hg during exercise.     

Left ventricular performance in children: transthoracic versus transoesophageal measurement of M mode derived indices

Objective—To compare M mode derived indices of left ventricular performance obtained with transthoracic and transoesophageal echocardiography in children with congenital heart disease.

Design—Transthoracic and transoesophageal M mode echocardiograms were obtained under general anaesthesia before cardiac catheterisation. Recordings were digitised by dedicated software. Indices of cavity dimension and left ventricular wall dynamics were compared.

Patients—16 unselected patients with congenital heart disease.

Results—Group data for simple measurements of ventricular dimension and wall thickness were similar with the two techniques and had acceptable coefficients of repeatability, but there were considerable individual differences. Correlation was poor with unacceptable repeatability for derived indices of cavity and ventricular wall dynamics.

Conclusion—Both transthoracic and transoesophageal echocardiography can be used to obtain M mode derived indices of left ventricular performance but the resultant measurements are not directly comparable, presumably because of regional non-uniformity of function.

     

Effects of verapamil and nifedipine on rate of left ventricular relaxation in coronary arterial disease patients

We have evaluated the effects of nifedipine and verapamil on rate of left ventricular relaxation in 26 patients having coronary arterial disease with normal ejection fraction and normal left ventricular contractility. None of the patients had myocardial infarction. All patients showed normal contractile indices and abnormally high values of T constant, neg, dP/dt and left ventricular protodiastolic pressure, suggesting an impairment of left ventricular relaxation. Nifedipine, injected intravenously (15 micrograms/kg) in 14 patients induced a significant reduction of afterload parameters and an increase of contractility. Nifedipine also improved left ventricular relaxation, as it induced a reduction of the T constant from 42 +/- 2 msec to 33 +/- 2 msec (P less than 0.01). It induced a tendency to a reduction of negative dP/dt and protodiastolic pressure without reaching statistical significance. Verapamil, injected intravenously in the remaining 12 patients (0.1 mg/kg as a bolus followed by chronic infusion of 0.005 mg/kg/min for 3 min) induced a reduction of the T constant from 43 +/- 10 to 37 +/- 6 msec (P less than 0.01). It reduced the negativity of dP/dt from 2302 +/- 273 to 2021 +/- 252 mm Hg/sec (P less than 0.05) and of left ventricular protodiastolic pressure from 3.2 +/- 1.4 to 1.5 +/- 1.1 mm Hg (P less than 0.01). Verapamil, like nifedipine, reduced the afterload parameters although to a lesser extent. It did not substantially affect the left ventricular contractility. These data suggest that abnormalities of left ventricular relaxation may precede changes in systolic function and that nifedipine and verapamil favourably modify the indices of left ventricular diastolic function in patients with coronary arterial disease.