Christine O'Sullivan

Effects of acute coronary occlusion and previous ischaemic injury on left ventricular wall motion in humans.

OBJECTIVE: To assess the acute effects of single and repeated coronary artery occlusions, during percutaneous transluminal coronary angioplasty (PTCA), on left ventricular long axis function in patients with stable and unstable angina. DESIGN: Prospective examination of ventricular systolic and diastolic long axis function using M mode echocardiography and transmitral Doppler in patients with significant coronary artery stenosis and either stable or unstable angina, during routine PTCA. SETTING: A tertiary referral centre for heart disease with cardiac catheterisation and echocardiographic facilities. SUBJECTS: 36 patients, age (SD) 60 (8) years, with significant coronary artery disease undergoing PTCA (mean duration 100-130 seconds) to the left anterior descending coronary artery (LAD) in 18 patients, native LAD or its vein graft in eight, and right coronary artery in 10. Controls were 21 normal subjects, age 58 (11) years. RESULTS-AT BASELINE: in systole, total long axis excursion was reduced at septal, posterior, and right sites in patients with LAD disease, at right site in those with vein grafts, and at septal and right sites in patients with right coronary artery disease. Peak shortening rate was often reduced in all patients and onset of shortening delayed with respect to the Q wave in patients with LAD disease. In diastole, onset of lengthening was always delayed, peak lengthening rate reduced, and relative A wave amplitude increased in all patients. There was a consistent abnormal shortening of the long axis during the isovolumic relaxation period in the 14 patients with unstable angina, not seen in the others. Transmitral A wave velocity was also increased and the onset of E wave delayed with respect to A2. At first balloon inflation: the extent of pre-existing systolic and particularly diastolic abnormalities consistently increased in patients with LAD or right coronary artery occlusion. This was associated with further delay in the onset of the transmitral Doppler E wave as its peak velocity fell and E/A ratio increased. In unstable angina, balloon inflation caused minor changes only in systolic function and no change in diastolic function. At second balloon inflation: systolic changes were the same as with the first inflation, while diastolic changes were attenuated by 10-15%. CONCLUSIONS: In stable angina intracoronary balloon inflation aggravated pre-existing systolic and diastolic abnormalities in the territory of the occluded vessel, indicating the dependence of both on coronary flow. In unstable angina balloon inflation caused only minor deterioration in systolic function, and diastolic changes-including the characteristic abnormal shortening during isovolumic relaxation-were unaffected. Thus resting abnormalities of left ventricular function in unstable angina are effectively dissociated from acute changes in coronary flow. Overall, the severity of systolic disturbances was unaltered by a second balloon inflation, but diastolic disturbances were attenuated by 10-15%, compatible with ischaemic preconditioning or recruitment of collaterals.

Left ventricular long axis disturbances as predictors for thallium perfusion defects in patients with known peripheral vascular disease

Objective To compare resting long axis echocardiography with adenosine thallium-201 emission tomography in detecting myocardial ischaemic abnormalities in patients before peripheral vascular surgery. Design A prospective and blinded preoperative examination of resting left ventricular minor and long axes and myocardial perfusion during adenosine vasodilatation using thallium-201 emission tomography. Setting A tertiary referral centre for cardiac and vascular disease equipped with invasive, non-invasive, and surgical facilities. Subjects 65 patients (40 men) with significant peripheral vascular disease, mean (SD) age 63 (10) years, and 21 control subjects of similar age. Methods Segments were classified as normal, with fixed or reversible defects according to thallium-201 myocardial perfusion tomography. Systolic long axis abnormalities were either reduced excursion and/or abnormal shortening after A2, and diastolic abnormalities either delayed onset of lengthening > 80 ms and/or reduced peak lengthening rate < 4.5 cm/s. Segmental perfusion defects were compared with the equivalent long axes; anteroseptal for septal, inferoseptal for posterior, and lateral for left side giving a total of 195 segments. Results Systolic long axis abnormalities predicted fixed thallium defects (sensitivity 86%, specificity 87%, positive predictive value 0.78, negative predictive value 0.93, p < 0.001), and diastolic abnormalities correlated with reversible perfusion defects (sensitivity 90%, specificity 85%, positive predictive value 0.72, negative predictive value 0.95, p < 0.001). Echocardiography characteristics of the true and false positive segments were not different in the site or the extent of abnormalities. Conclusion Systolic long axis abnormalities predict fixed and diastolic reversible thallium perfusion defects in patients with peripheral vascular disease. Ventricular long axis may thus have a value as a screening test before peripheral vascular surgery as well as providing a means of monitoring myocardial perfusion. The high negative predictive values indicate that a negative long axis study makes significant perfusion abnormalities very unlikely in patients with high pretest probability of coronary artery disease.

Abnormal ventricular activation and repolarisation during dobutamine stress echocardiography in coronary artery disease

Objective To assess possible ECG changes caused by dobutamine stress and their relation to wall motion disturbances in patients with coronary artery disease. Design Prospective recording and analysis of 12 lead ECG at rest and during each stage of dobutamine stress echocardiography, and correlation with wall motion changes. Setting A tertiary referral centre for cardiac disease equipped with non-invasive facilities for pharmacological stress tests. Subjects 27 patients, mean (SD) age 60 (8) years, with documented evidence of coronary artery disease in whom dobutamine stress echo was clinically indicated, and 17 controls of similar age. Results In controls, all ECG intervals shortened with increasing heart rate but in the patient group only PR and QT intervals shortened while QRS duration broadened and QTc interval prolonged progressively. In the 27 patients, 16 developed chest pain, 15 with reduced left ventricular long axis systolic excursion (p < 0.001), and all showed reduced peak lengthening rate; ST segment shift appeared in 16, 13 of whom developed chest pain, but did not correlate with reduction of either systolic long axis excursion or peak lengthening rate; QRS duration broadened in 20, 16 with reduction of long axis excursion (p < 0.02) which was more often seen at the septum (p < 0.005); QTc interval prolonged in 19, all of whom had associated reduction of peak long axis lengthening rate (p < 0.02). Conclusions QRS duration and QTc interval both normally shorten with dobutamine stress, while in coronary artery disease they both lengthen: changes in QRS duration correlate with systolic and QTc interval with diastolic left ventricular wall motion disturbances. ST segment shift also occurred in most patients, but without consistent correlation with wall motion abnormalities. It was thus less discriminating than the other two abnormalities in this respect.

Electromechanical interrelations during dobutamine stress in normal subjects and patients with coronary artery disease: comparison of changes in activation and inotropic state

OBJECTIVE To identify the effects of altered ventricular activation during dobutamine stress on left ventricular function in normal subjects and in patients with coronary artery disease, and to distinguish these from an inotropic response. DESIGN Prospective analysis of 12 lead ECG and echocardiogram at rest and at peak stress. SETTING Tertiary referral centre for cardiac disease equipped with non-invasive facilities for pharmacological stress testing. METHODS 22 patients with coronary artery disease were compared with 17 age matched controls. Left ventricular ejection and filling patterns were assessed using Doppler echocardiography. Activation effects were correlated with relative left ventricular ejection and filling times, and the Z ratio ([left ventricular ejection + filling times]/RR interval). Inotropic response was measured from peak aortic acceleration. RESULTS In controls, QRS shortened (by 4 ms, p < 0.001), and total ejection and filling periods lengthened (by 2 s/min, p < 0.01 and 5 s/min, p < 0.001, respectively). The Z ratio thus increased and correlated with QRS shortening (r 2 = 0.69). Peak aortic acceleration (PAA) increased by 135%, p < 0.001. In patients, QRS lengthened at peak stress (by 9 ms, p < 0.001). Total ejection and filling times did not change, but Z ratio fell, correlating with QRS prolongation (r 2 = 0.65). Nevertheless, PAA increased by 63%, p < 0.001. CONCLUSIONS Relative ejection and filling times reflect ventricular activation at rest and during stress independent of changes in inotropic state. By contrast, peak aortic acceleration reflects the positive inotropic effect of dobutamine on the myocardium, regardless of changes in activation.

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.

Heart rhythms, ventricular arrhythmias, and death in chronic heart failure.

BACKGROUND The aim of this study was to evaluate whether abnormalities in heart rate variability (HRV) could act as markers of ventricular tachycardia and prognosis in patients with advanced, chronic heart failure. Fifty patients with chronic heart failure (45 men; mean age, 59 +/- 9 years; New York Heart Association [NYHA] class II-III; left ventricular ejection fraction [LVEF], 19 +/- 9% and peak oxygen consumption, 16.6 +/- 5.4 mL/kg/min) caused by idiopathic dilated cardiomyopathy (n = 12) and ischemic heart disease (n = 38) were included in the study. Heart rate variability measures derived from 24-hour electrocardiographic (ECG) monitoring (Marquette 8500 recorder, Marquette Electronics, Milwaukee, WI) were calculated in the time domain and frequency domain. METHODS AND RESULTS Twenty-five patients (50%) revealed episodes of ventricular tachycardia on 24-hour ECG monitoring (1-143 episodes). The presence of ventricular tachycardia was associated with lower LVEF but there was no difference in NYHA class and peak oxygen consumption between patients with and without ventricular tachycardia (LVEF, 16 vs 22%, P = .01; NYHA class, 2.6 vs 2.4; peak oxygen consumption, 16.5 vs 16.8 mL/kg/min, not significant). Patients with ventricular tachycardia exhibited markedly lower HRV measures. Multiple regression analysis was used to test HRV parameters as potential predictors of ventricular tachycardia. Among them, high-frequency power was the only independent predictor of the presence of ventricular tachycardia, and this predictive correlation was independent of LVEF and mean R-R interval duration. During a follow-up period of 24 +/- 18 months, 12 patients (24%) died. No difference was found in age, etiology, NYHA class, peak oxygen consumption, or occurrence of ventricular tachycardia, but a lower LVEF (15 +/- 6 vs 21 +/- 9%, P = .046) was observed in those who died compared with those who survived. Certain estimates of HRV were in contrast, lower in those who subsequently died: standard deviation of all normal R-R intervals (61 +/- 30 vs 101 +/- 33 ms), standard deviation of 5-minute mean R-R intervals (55 +/- 27 vs 92 +/- 31 ms), mean of all 5-minute standard deviations of R-R intervals (22 +/- 12 vs 37 +/- 11 ms), and the low-frequency (3.2 +/- 1.8 vs 4.8 +/- 0.9 ln ms2) and high-frequency (3.0 +/- 1.1 vs 3.8 +/- 0.8 ln ms2) components of the HRV spectrum (all differences, P < .01). In univariate Cox analysis, all of these HRV measures were independent predictors of death. Kaplan-Meier survival analysis revealed that the standard deviations of all normal R-R intervals and of 5-minute mean R-R intervals dichotomized at median values (99 and 90.5 ms, respectively) were the best predictors of mortality. CONCLUSIONS In patients with moderate to severe chronic heart failure, depressed indices of HRV on 24-hour ambulatory ECG monitoring could be related to higher risk of ventricular tachycardia and death, suggesting that analysis of HRV could be usefully applied to risk stratification in chronic heart failure patients.

Effect of acute alterations in afterload on left ventricular function in patients with combined coronary artery and peripheral vascular disease.

OBJECTIVE: To assess the effect of acute alterations in afterload by aortoiliac clamping, during peripheral vascular surgery, on left ventricular function. DESIGN: Prospective examination of the left ventricular long axis and transmitral Doppler flow preoperatively and intraoperatively; before aortic clamping, during clamping and 5 min, 15 min, and 5 days after unclamping. SETTING: A tertiary referral centre for cardiac and vascular disease equipped with invasive and non-invasive facilities. PATIENTS: 20 patients (11 men; mean (SD) age 61 (8) years) with significant aortoiliac disease and documented coronary artery disease and 21 normal controls of similar age. RESULTS: Preoperatively: long axis function was abnormal compared with that in normal controls. In systole total long axis excursion and peak shortening rate were reduced, onset of shortening delayed, and there was pre-ejection lengthening (P < 0.001). In diastole there was abnormal shortening during isovolumic relaxation, delaying the onset of long axis lengthening (P < 0.001). Peak lengthening rate was also reduced and A wave excursion increased (P < 0.001). Transmitral Doppler showed increased A wave velocity and reduced peak E/A diastolic flow velocities ratio (P < 0.001). Intraoperatively: preclamping results did not differ from those before operation. With clamping the extent of systolic and diastolic abnormalities promptly increased as to a lesser extent did those of transmitral flow velocity, although heart rate and blood pressure did not change significantly. Total long axis excursion and A wave amplitude were more reduced by aortic than iliac clamping, whereas the onset of lengthening was more delayed and the lengthening velocity more reduced with iliac clamping. Some 5 min after unclamping systolic long axis function had already returned towards normal; total excursion increased, as did the peak shortening rate, and the onset of shortening became less delayed (P < 0.001). In diastole the delayed onset of lengthening regressed, its lengthening velocity increased, and A wave excursion fell (P < 0.001). Early diastolic transmitral flow velocity also increased. This improvement in systolic and diastolic long axis function had progressed 15 min after unclamping but showed no further change at 5 days. At 5 days after operation, however, systolic and diastolic measurements had improved compared with those preoperatively. CONCLUSION: Resting left ventricular long axis function is abnormal in patients with combined coronary artery disease and peripheral vascular disease. It is unaffected by anaesthesia but deteriorates with aortic or iliac clamping, although blood pressure remains unchanged. It promptly improves with unclamping after successful peripheral arterial reconstruction. Thus, even in apparently stable coronary artery disease, resting subendocardial function is labile, showing pronounced alterations with changing after-load, even when arterial pressure itself does not change.

Incremental importance of peak-exercise plasma levels of endothelin-1 and natriuretic peptides in chronic heart failure

&NA; Chronic heart failure (CHF) studies investigating the clinical, hemodynamic, and therapeutic importance of endothelin‐1 (ET‐1), atrial natriuretic peptide (ANP), and brain natriuretic peptide (BNP) are largely based on resting plasma levels, which may vary with prior exertion and postprandial status. This study investigated the importance of peak‐exercise plasma levels of ET‐1, ANP, and BNP in the assessment of left ventricular (LV) systolic function. Thirty‐six male‐patients ages 58 ± 10 (mean ± SD ) with NYHA class I‐IV CHF due to coronary artery disease or idiopathic dilated cardiomyopathy were enrolled. LV systolic function was assessed by echocardiography and radionuclide ventriculography. Resting and peak cardiopulmonary exercise venous blood sampling and treadmill exercise testing were performed in the fasting state. Resting plasma levels of ET‐1, ANP, and BNP were elevated compared with reference laboratory normal values. Exercise induced significant (p < 0.0001) increase in plasma levels of ET‐1, ANP, and BNP. On univariate analysis peak‐exercise plasma levels of ET‐1, ANP, and BNP were more closely related to echocardiographically determined LV end‐diastolic diameter and end‐systolic diameter than their resting values. Multiple step‐wise regression models identified resting and peak‐exercise plasma levels of ET‐1 and ANP but only the resting BNP as independent predictors of LV dimensions and systolic function. Peak exercise plasma levels of ANP and ET‐1 are potentially more reliable and important than their resting levels as markers of LV systolic dysfunction and LV dimensions in patients with heart failure.

Right ventricular stunning in inferior myocardial infarction

AIM To assess right ventricular (RV) function in patients with inferior myocardial infarction (IMI) and to observe changes following thrombolysis. BACKGROUND RV dysfunction occurs in 30% of patients with IMI. The extent of such involvement and its potential, recovery has not been determined. METHODS We studied 30 patients with acute IMI (age 56+/-12 years), on admission, day 7 and day 30 post thrombolysis. No patient had clinical signs of RV failure. RV segmental function was assessed from free wall long axis and global function from filling and ejection velocities. Values were compared with 15 age-matched controls. RESULTS On admission, RV long axis amplitude, systolic and diastolic velocities were depressed (2.09+/-0.39 vs 2.6+/-0.3 cm, 8.18+/-1.8 vs 10.0+/-2.0 cm/s and 6.9+/-2.7 vs 10.0+/-2.5 cm/s, p<0.01 for all) and global function impaired; reduced Z ratio (0.85+/-0.07 vs 0.9+/-0.04, p<0.01), raised Tei index (0.49+/-0.26 vs 0.3+/-0.1, p<0.001) and prolonged t-IVT (8.16+/-3.9 vs 4.8+/-2 s/m, p<0.01) compared to controls. After thrombolysis, RV long axis amplitude (2.28+/-0.3 cm, p<0.05), systolic velocity (10.0+/-2.7 cm/s, p<0.01), early diastolic velocity (8.3+/-2.16, p<0.05), Z ratio (0.9+/-0.05, p<0.01), Tei index (0.34+/-0.17, p<0.01) and t-IVT (6.2+/-2.7 s/m, p<0.05) all normalised at day 30. Only 4 (13%) patients remained with RV long axis amplitude and one with t-IVT and Tei index values outside the normal 95% CI at day 30. RV inflow diameter and tricuspid regurgitation did not change. CONCLUSION In IMI, RV segmental and global functions are acutely impaired, and recover in 87% of patients following thrombolysis. In the absence of clear evidence for RV infarction the disturbances in the remaining 13% may represent stunned myocardium that may demonstrate delayed recovery.