A reduction in total isovolumic time with cardiac resynchronisation therapy is a predictor of clinical outcomes.

BACKGROUND: Total isovolumic time (t-IVT) reflects left ventricular (LV) asynchrony (when the ventricle is neither ejecting nor filling). It is prolonged in left bundle branch block (LBBB). Cardiac resynchronisation therapy (CRT) is a treatment for patients with heart failure, reduced LV ejection fraction and LBBB. CRT shortens t-IVT, but the long-term clinical benefit of such reduction after CRT has not been studied in this patient group. METHODS: Seventy-three patients who underwent CRT had t-IVT measured before and after CRT implantation. The study end-point was a composite of unplanned heart failure hospitalisation and all-cause mortality. RESULTS: Baseline t-IVT showed considerable scatter: 30 patients had t-IVT values longer than 15s/min (upper 95% limit of normal). The change in t-IVT with CRT was also variable: t-IVT shortened in 50 patients (from 16.2 ± 4.8s/min to 11.7 ± 3.7s/min: group A), and lengthened in 23 patients (from 11.7 ± 4.2s/min to 14.5 ± 4.33 s/min: group B). The magnitude of change in t-IVT with CRT negatively correlated with baseline t-IVT (r=-0.619, p<0.001); thus t-IVT (significantly longer in group A than group B before CRT: 16.2 ± 4.8s/min vs. 11.7 ± 4.2s/min, p<0.001) became significantly shorter in group A compared to group B after CRT (11.7 ± 3.7s/min vs. 14.5 ± 4.3s/min, p=0.005). After follow-up of 30 months, 70% group A patients had event-free survival compared to 39% group B patients. The presence of any fall in t-IVT after CRT was an independent predictor of event-free survival. CONCLUSION: T-IVT is a marker of global cardiac asynchrony that has predictive capacity on functional, symptomatic, and mortality endpoints in patients with advanced heart failure.

Randomised trial of ramipril in repaired tetralogy of Fallot and pulmonary regurgitation: the APPROPRIATE study (Ace inhibitors for Potential PRevention Of the deleterious effects of Pulmonary Regurgitation In Adults with repaired TEtralogy of Fallot).

BACKGROUND: Optimal treatment for stable repaired tetralogy of Fallot (rTOF) patients with pulmonary regurgitation (PR) and related right ventricular (RV) dilatation, including timing of valve implantation, remains uncertain. We sought to study tolerability of the angiotensin-converting-enzyme (ACE) inhibitor ramipril and its effects on cardiovascular function in these patients. METHODS: Clinically stable rTOF patients with moderate/severe PR were included. A double-blinded, placebo-controlled study of 6 months of ramipril vs placebo was performed. All patients underwent cardiovascular magnetic resonance (CMR), echocardiography, neurohormonal analysis, and objective cardiopulmonary exercise testing at baseline and follow-up. PRIMARY ENDPOINT: The main aim was to detect changes in RV function (primary endpoint CMR-derived RV ejection fraction). RESULTS: Seventy-two patients were enrolled and 64 qualified for the final analysis. There was no difference in the primary endpoint RV ejection fraction. RV long-axis shortening significantly improved in the ramipril group compared to placebo (RV: 2.3 ± 3.8 vs 0.02 ± 2.7 mm; P=0.017) as did LV long-axis shortening (1.9 ± 4.5 vs -0.2 ± 3.7 mm respectively; P=0.030). No clear differences were detected between ramipril and placebo for other measures. In a subgroup of patients with restrictive RV physiology, ramipril resulted in decrease in LV end-systolic volume index and increase in LVEF (-2.4 ± 5.0 vs 2.7 ± 3.6 mL/m(2); P=0.005, 2.5 ± 5.0 vs -1.3 ± 3.5%; P=0.03). Ramipril did not cause adverse events and was well tolerated. CONCLUSIONS: Ramipril is a well tolerated therapy, improves biventricular function in patients with rTOF and may have a particular role in patients with restrictive RV physiology. Larger, longer-term studies are needed to determine if ACE inhibitors can improve both ventricular remodelling and clinical outcomes. ( ISRCTN: 97515585).

Total isovolumic time relates to exercise capacity in patients with transposition of the great arteries late after atrial switch procedures.

BACKGROUND: Systemic right ventricular systolic dysfunction is common late after atrial switch surgery for transposition of the great arteries. Total isovolumic time is the time that the ventricle is neither ejecting nor filling and is calculated without relying on geometric assumptions. We assessed resting total isovolumic time in this population and its relationship to exercise capacity. METHODS: A total of 40 adult patients with transposition of the great arteries after atrial switch - and 10 healthy controls - underwent transthoracic echocardiography and cardiopulmonary exercise testing from January, 2006 to January, 2009. Resting total isovolumic time was measured in seconds per minute: 60 minus total ejection time plus total filling time. RESULTS: The mean age was 31.6 plus or minus 7.6 years, and 38.0% were men. There were 16 patients (40%) who had more than or equal to moderate systolic dysfunction of the right ventricle. Intra- and inter-observer agreement was good for total isovolumic time, which was significantly prolonged in patients compared with controls (12.0 plus or minus 3.9 seconds per minute versus 6.0 plus or minus 1.8 seconds per minute, p-value less than 0.001) and correlated significantly with peak oxygen consumption (r equals minus 0.63, p-value less than 0.001). The correlation strengthened (r equals minus 0.73, p-value less than 0.001) after excluding seven patients with exercise-induced cyanosis. No relationship was found between exercise capacity and right ventricular ejection fraction or long-axis amplitude. CONCLUSION: Resting isovolumic time is prolonged after atrial switch for patients with transposition of the great arteries. It is highly reproducible and relates well to exercise capacity.

Underestimation of duration of ventricular activation by 12-lead ECG compared with direct measurement of activation duration derived from implanted pacemaker leads.

AIM: To determine extent to which 12-lead ECG QRS duration (QRSd) reflects ventricular activation duration compared with time relations from unpaced ventricular myograms in cardiac resynchronisation therapy (CRT) patients. METHODS: Left (LV) and right ventricular (RV) myograms were recorded during spontaneous rhythm from in-situ pacemaker leads in 77 patients receiving CRT; 14 'normal activation' (unpaced QRSd <12 ms), 10 'simple left bundle branch block' (LBBB, QRSd 120-149 ms), 40 'advanced LBBB' (QRS ≥ 150 ms) and 13 right bundle branch block. Delay in onset (Q-LV, Q-RV) and duration (dur-LV, dur-RV) of activation were measured. Interventricular delay (ΔT: Q-LV minus Q-RV) and 'LV-overrun' (time between end 12-lead QRS and Q-end LV myogram) were calculated. RESULTS: 'Normal activation': Neither Q-LV, Q-RV (38 ± 6 ms, 39 ± 11 ms), nor dur-LV, dur-RV (66 ± 9 ms, 81 ± 25 ms) differed. ΔT (-1 ± 11 ms) was not different from zero, nor was Q-end LV (104 ± 10 ms) different from QRSd (p=0.09). 'Simple LBBB': Q-LV (102 ± 28 ms) was longer than 'normal activation' (p<0.001), but Q-RV, dur-LV, and dur-RV were no different. ΔT (54 ± 23 ms) was increased (p<0.001) and Q-end LV (187 ± 48 ms) was longer than QRSd (p=0.005). 'Advanced LBBB': Q-LV (115 ± 52 ms) was longer than 'normal activation' (p<0.001) but Q-RV was no different, so ΔT (72 ± 47 ms) was increased (p<0.001 compared to normal, p=0.04 compared to simple LBBB). Dur-LV (102 ± 27 ms) was also prolonged, so Q-end LV (218 ± 48 ms) was longer than QRSd (p<0.001). Longer LV-overrun was associated with longer ΔT (p<0.001). CONCLUSIONS: Prolonged LV myopotential duration, associated with interventricular delay, is electrically silent on 12-lead QRSd. Unpaced surface QRSd underestimates true duration of native LV activation in CRT patients.

Right ventricular mechanics and QRS duration in patients with repaired tetralogy of Fallot: implications of infundibular disease.

BACKGROUND: Patients after repair of tetralogy of Fallot (ToF) frequently have right ventricular (RV) dysfunction and prolonged QRS duration (QRSd) and thus could be candidates for cardiac resynchronization therapy. We aimed to assess the relationship between QRSd and the timing of RV wall motion, including the RV outflow tract (RVOT), in these patients. METHODS AND RESULTS: Sixty-seven repaired ToF patients (median age, 34 years; interquartile range, 24 to 43 years) and 35 age-matched control subjects were studied by echocardiography and cardiovascular magnetic resonance (n=55 of 67 ToF patients). Time intervals of the RV cardiac cycle were measured from Doppler recordings. Long-axis M-mode recordings were acquired from the right ventricular (RV) free wall and RV outflow tract (RVOT), and the delay in onset of long-axis shortening was measured. ToF patients showed minor abnormalities of the RV cardiac cycle unrelated to QRSd. RV ejection time was prolonged and correspondingly filling time was reduced compared with control subjects (22.3+/-2.6 versus 20.0+/-2.9 s/min, P<0.0001; 29.0+/-3.8 versus 32.7+/-3.5 s/min, P<0.0001). Total isovolumic time was normal in ToF patients (8.7+/-4.0 versus 7.4+/-2.9 s/min; P=NS). QRSd correlated with the delay in RV free wall motion (r=0.55, P<0.0001) and more so with the delay in RVOT shortening (r=0.82, P<0.0001). QRSd also correlated with measures of RVOT abnormality such as long-axis RVOT excursion and akinetic area length (r=-0.46, P=0.004; r=0.33, P=0.01). CONCLUSIONS: QRSd in postoperative ToF patients reflects mainly abnormalities of the RVOT rather than the RV body itself. Thus, prevention and treatment of mechanical asynchrony and malignant arrhythmia should focus on the RV infundibulum. Indications for cardiac resynchronization therapy after ToF repair warrant further investigation.

The right ventricular response to high afterload: comparison between atrial switch procedure, congenitally corrected transposition of the great arteries, and idiopathic pulmonary arterial hypertension.

BACKGROUND: We aimed to define differences between systemic right ventricle (RV) in patients with atrial switch procedure for transposition of the great arteries, and congenitally corrected transposition of the great arteries (ccTGA), which remodels early on in life and the subpulmonary RV in patients with idiopathic pulmonary arterial hypertension (iPAH) which remodels later in adulthood to the effects of progressive pulmonary hypertension. METHODS: Prospective echocardiographic assessment of consecutive patients with atrial switch procedure, ccTGA, and iPAH attending adult congenital heart program. Right ventricular long axis function by M-mode and tissue Doppler imaging; myocardial performance index; and total isovolumic time (t-IVT), ventricular filling time, and ejection time (ET) were studied and compared with normal left ventricle and RV. RESULTS: Seventy-eight patients (20 atrial switch, 18 ccTGA, 20 iPAH, and 20 normal) were studied. Right ventricular long axis function was most reduced after atrial switch procedure. Diastolic filling and dysfunction varied across the groups, with atrial switch patients having the lowest myocardial early diastolic (Em) and atrial diastolic (Am) velocities and iPAH patients with the longest t-IVT, shortest filling time and ET, and lowest Em/Am, reflecting predominantly late diastolic filling. Patients with ccTGA had better preserved global systemic RV systolic and diastolic indices. CONCLUSION: The RV develops adaptative mechanisms when faced with increased afterload, behaving more like normal left ventricle. This adaptation is closer when present from birth (ccTGA) without facing subsequent surgical insults. In iPAH, the RV adapts poorly, showing prolonged t-IVT and shortened filling and effective ETs, eventually resulting in lower stroke volume and overall poorer prognosis.

Comparison of segmental and global markers of dyssynchrony in predicting clinical response to cardiac resynchronization.

AIMS: Cardiac resynchronization therapy (CRT) reduces inter- and intraventricular dyssynchrony and shortens total isovolumic time (t-IVT). We compared the extent to which the values of ventricular dyssynchrony and t-IVT predict clinical benefits of CRT. METHODS AND RESULTS: Ventricular dyssynchrony was assessed in 39 patients with heart failure before and 6 months after CRT. Segmental dyssynchrony was identified from time to onset and peak systolic velocity of wall motion. T-IVT (s/min) was derived as [60-(total ejection time+total filling time)]. The difference between ventricular pre-ejection periods (D-PEP) was calculated. Outcome measures were fall in New York Heart Association (NYHA) class and increase in cardiac output (CO). Following CRT, NYHA class fell in 29/39 patients, CO increased (by 1.0 L/min, P < 0.001), and intraventricular delay (Intra-VD), interventricular delay (Inter-VD), t-IVT, and D-PEP shortened (by 25 ms, 72 ms, 6 s/min, and 38 ms, P < 0.01). NYHA class and CO were unchanged with CRT in 10/39, and Intra-VD, Inter-VD, t-IVT, and D-PEP lengthened (by 43 ms, 52 ms, 7 s/min, and 35 ms, P < 0.05). Though univariate predictors of CO increment with CRT were Intra-VD, Inter-VD, t-IVT, and D-PEP, only pre-CRT values of CO (P < 0.001), t-IVT (P < 0.001), and D-PEP (P = 0.025) were independent. CONCLUSION: Global, rather than segmental, measures of ventricular dyssynchrony are powerful, independent predictors of clinical response to CRT.

Regional ventricular dynamics during acute coronary occlusion: a comparison of invasive with non-invasive echocardiographic markers to detect and quantify myocardial ischaemia-observations made during off-pump coronary surgery.

OBJECTIVES: To investigate the performance of non-invasive markers used in stress echocardiography to detect the presence and depth of myocardial ischaemia. We therefore sought to compare these non-invasive markers during acute coronary occlusion in humans. METHODS: 27 patients with stable angina and normal LV cavity size were studied during off-pump coronary artery bypass grafting to the left anterior descending coronary artery using transoesophageal echocardiography and simultaneous high fidelity LV pressure. Regional power development of the anterior wall was plotted throughout the cardiac cycle, allowing the measurement of its time course, peak value and time integral (intrinsic work). Regional effective myocardial work was calculated and its reduction during acute occlusion was used as the invasive standard for ischaemic dysfunction. RESULTS: In all patients acute coronary occlusion led to a delay in the onset of regional wall thickening which persisted after aortic valve closure. These time intervals of myocardial thickening had the highest qualitative concordance with the gold standard of a fall in effective work. Regression models identified three significant predictors of the depth of myocardial ischaemia; the interval from Q wave to the onset of regional thickening, duration of post-ejection thickening and peak thickening rate. Objective wall thickening and thinning rates were not significant predictors. CONCLUSIONS: The regional timing of myocardial thickening and peak thickening rate accurately predicted the presence and indicated the depth of local ischaemia during acute coronary occlusion. These markers may complement subjective wall motion scores aimed at predicting the presence of epicardial coronary artery disease. CONDENSED ABSTRACT: We compared non-invasive markers commonly used in stress echocardiography using measurements of the fall in regional myocardial work with coronary occlusion as a standard. 27 patients were studied using transoesophageal echocardiography and simultaneous high fidelity left ventricular pressure during off-pump coronary surgery. Delayed myocardial thickening had the highest qualitative concordance with the gold standard of a fall in effective work, while regression models identified three significant predictors; the interval Q wave to the onset of regional thickening, duration of post-ejection thickening and peak thickening rate. These markers may complement current non-invasive indices of ischaemia during clinical stress testing.

Effect of dobutamine stress on left ventricular filling in ischemic dilated cardiomyopathy: pathophysiology and prognostic implications.

OBJECTIVES: The purpose of this research was to study the effect of dobutamine on left ventricular (LV) filling in ischemic cardiomyopathy (ICM) and to determine whether restrictive filling pattern (RFP) at peak stress has prognostic value. BACKGROUND: The prognostic value of RFP at peak stress in ICM is unknown. METHODS: A total of 69 patients with ICM were studied by Doppler echocardiography at rest and stress; RFP was defined as transmitral E:A ratio > or =1.0, isovolumic relaxation time (IVRT) <80 ms, and E-wave deceleration time (EDT) <120 ms. RESULTS: A total of 42 of 69 had RFP at rest, which reverted to non-RFP at stress in 24 (EA), but persisted in 18 (EE); 27 of 69 had non-RFP at rest and peak stress (AA). In EA, IVRT and EDT lengthened (by 43 ms and 46 ms), and tricuspid regurgitation (TR) decreased (by 26 mm Hg, p < 0.01), suggesting a fall in left atrial (LA) pressure. The stress response in AA was similar to EA. In EE, IVRT and EDT shortened (by 21 ms) and TR increased (by 13 mm Hg, p < 0.01), suggesting a rise in LA pressure. Peak aortic acceleration (LV inotropy) increased by 0.8 g in EA but only by 0.2 g in EE (difference p < 0.001). Median follow-up (interquartile range) was 34 (20 to 57) months. Three-year survival for EE, EA, and AA was 49%, 79%, and 89%, respectively (p < 0.001). Compared with AA, the hazard ratio for EE was 9.5 (p < 0.001) and for EA was 1.9 (p = 0.30). CONCLUSIONS: In ischemic cardiomyopathy, persistence of restrictive filling during stress implies a striking rise in LA pressure, greatly attenuated LV inotropic response, and markedly reduced survival. Stress echocardiography uniquely identifies these high-risk patients.

Characteristics of ischaemic human myocardium: a transoesophageal echocardiographic and voltammetric microelectrode study.

Delayed local myocardial power development (primary asynchrony) has been suggested as a marker of ischaemic ventricular dysfunction in humans. However, to prove this, microcirculatory perfusion, microcirculatory oxygenation, and intrinsic mechanical function of the same asynchronous myocardial segment should be studied simultaneously before and after revascularisation. We performed a prospective intraoperative study of 15 patients (age 67 [SD 5] years) at baseline and 30 min after left anterior descending artery grafting. Local tissue perfusion and oxygenation of the anterior left ventricular wall were quantified with a voltammetric microelectrode technique. Transesophageal M-mode echocardiograms and simultaneous high-fidelity left ventricular pressure were measured. Eight patients showed primary asynchrony and 7 did not. Patients with primary asynchrony had local mechanical depression with lower resting values of myocardial work and peak power which increased with surgery. In this group, resting perfusion consistently increased with surgery (32.1 [13] to 54 [31] ml min(-1) 100 g(-1), P < 0.05). In the remaining patients, local work and power were normal, and resting perfusion was consistently higher (90 [9] Ml min(-1) 100 g(-1), P < 0.05 vs primary asynchrony), and fell with surgery. Local tissue oxygen tension was similar in both groups (38 vs 44 mmHg) and did not change with surgery. In patients with chronic coronary artery disease, microcirculatory perfusion, but not pO2, is reduced in regions showing primary asynchrony and impaired mechanical function. Abnormalities in both mechanical function and perfusion normalise within 30 min of revascularisation. These data provide further evidence that primary asynchrony is not only a marker of chronic ischemic ventricular dysfunction, but is associated with a modified contraction pattern in which normal oxygen tension coexists with reduced perfusion.

Opposite effects of coronary artery disease and hypertrophic cardiomyopathy on left ventricular long axis function during dobutamine stress.

BACKGROUND: The mechanism for reduced early diastolic long axis lengthening velocity in hypertrophic cardiomyopathy (HCM) is not known. METHODS: We measured simultaneous septal long axis amplitude and early lengthening velocity in 23 patients with HCM, 23 normal subjects and 22 patients with coronary artery disease (CAD) of left anterior descending artery. RESULTS: Resting amplitude and lengthening velocity were reduced in HCM 0.9+/-0.2 cm, 3.5+/-1.9 cm/s but equally in CAD 1.0+/-0.3 cm, 4.1+/-2.5 cm/s vs. 1.3+/-0.2 cm, 6.3+/-1.7 cm/s in normals, p < 0.01 for both vs. normal. With dobutamine stress, lengthening velocity increased by 2.7+/-1.9 cm/s (p < 0.001) in normals, by 2.8+/-2.5 cm/s (p < 0.001) in HCM but not in patients with CAD 0.5+/-2.1, p = NS. Increment in total long axis amplitude was subnormal in CAD and HCM. However, increment in lengthening velocity was higher with stress for corresponding change in amplitude in HCM compared with CAD (chi2) = 16.5, p < 0.001). An increase in early lengthening velocity by 2 cm/s was 77% sensitive and 70% specific in discriminating between HCM and CAD. Post-ejection shortening developed or worsened in all CAD patients indicating ischemia but not in any with HCM. CONCLUSIONS: Reduced peak early lengthening velocity is not specific for HCM but also occurs in CAD. Unlike CAD, lengthening velocity increases in HCM with stress and there is no aggravation of post-ejection shortening, suggesting that the abnormal relaxation is not due to subendocardial ischemia in HCM. The greater recoil velocity per unit deformation in HCM compared with CAD, indicates elastic mechanism with increased passive muscle stiffness due to fibrosis or fibre disarray.

'Tamponade' following cardiac surgery: terminology and echocardiography may both mislead.

OBJECTIVE: Echocardiography is widely considered the gold standard for the diagnosis of tamponade. While a relatively common complication of cardiac surgery in adults, determining whether haemodynamics are compromised by a pericardial collection early post-operatively can be difficult. The aim of the current study was to determine the nature and magnitude of the diagnostic challenge posed by cardiac tamponade following cardiac surgery. We therefore examined the accuracy of echocardiography in the diagnosis of tamponade in this patient group. METHODS: From January 2000 to January 2002, 2297 adult patients underwent cardiac surgery in a tertiary referral cardiothoracic centre. A retrospective analysis of prospectively collected data, from all patients diagnosed with post-operative bleeding and/or tamponade was performed. Data included demographics, surgery, anticoagulation/anti-platelet medication, clinical/echocardiographic features of tamponade and surgical findings at re-exploration. RESULTS: The diagnosis of 'tamponade' was confirmed at re-exploration in 148 patients. When it occurred early (<72 h) following cardiac surgery trans-thoracic echocardiography failed to visualise the majority of collections (60%), necessitating trans-esophageal echocardiography. Effusions were small (160+/-17 ml) and localised (92%), showing no echocardiographic features of classical tamponade (79%). Where patients developed tamponade late (>72 h) following cardiac surgery, clinical features were atypical, effusions larger (640+/-71 ml, P<0.0001)) and global (77%). Classical echocardiographic features of tamponade were usually present (70%) and readily visualised using trans-thoracic echocardiography. CONCLUSIONS: Haemodynamically significant pericardial collections occurring early following cardiac surgery rarely cause classical clinical or echocardiographic features of tamponade. Recognition of this as a separate diagnostic entity is necessary to ensure appropriate surgical intervention is not delayed.

Systole-diastole mismatch in hypertrophic cardiomyopathy is caused by stress induced left ventricular outflow tract obstruction.

BACKGROUND: Pharmacological stress is used to assess the degree of left ventricular (LV) subvalvular gradient in patients with hypertrophic cardiomyopathy (HCM), but there is little information about associated physiological changes. METHODS: Echocardiography-Doppler ultrasound scanning measurements in 23 patients with HCM and 23 control subjects of similar age were studied at rest and at the end point of dobutamine stress. RESULTS: In patients, the systolic time was normal at rest, but increased abnormally with stress. In patients, the total isovolumic contraction time failed to shorten, and the total ejection time increased abnormally. Changes in total ejection time correlated with an increase in peak subvalvular gradient in control subjects and patients (r = 0.52 and r = 0.66, respectively; P <.01 for both). In patients, the diastolic time was normal at rest, but shortened abnormally with stress. In patients, the isovolumic relaxation time fell abnormally, as did the filling time. Mitral E wave acceleration and left atrium size were unchanged with stress in control subjects, but consistently increased in patients with HCM, which indicates an increased early diastolic atrioventricular pressure gradient. CONCLUSION: In HCM, systolic period increases abnormally with stress. This is not because of a loss of inotropy, but is directly related to the degree of LV outflow tract obstruction. As a result, the diastolic period fails to increase, reducing the time available for coronary flow, the LV filling pattern is modified, and the diastolic atrioventricular pressure gradient increases. These changes may contribute to symptom development and suggest why reducing LV outflow tract obstruction per se may be therapeutically useful in HCM.

Clinical in vivo calibration of pulse wave tissue Doppler velocities in the assessment of ventricular wall motion. A comparison study with M-mode echocardiography.

BACKGROUND: Pulsed Wave Tissue Doppler (PWTD) recording of myocardial velocities has been widely used for assessing ventricular function but the output trace has finite thickness that leads to potential ambiguity in determining velocity and timing. OBJECTIVE: To determine optimal method of measurement of PWTD traces by comparing them with those obtained from digitised M-mode recorded from the atrioventricular (AV) valve ring (septal, LV and RV free wall). METHODS: We studied 100 subjects, 49 normal and 51 with coronary artery disease (15 patients with reduced left ventricular wall motion, mean systolic amplitude of LV free wall 0.8+/-0.3 cm), mean age 53+/-15 years. We recorded AV ring motion using PWTD and M-mode echo techniques. PWTD velocity signals were measured separately at: outer, inner and mid-points of the envelope and compared with peak velocities obtained from digitised M-mode long axis. RESULTS: Peak systolic (S), early diastolic (E) and late diastolic (A) PWTD velocities at outer, inner and middle envelope correlated closely with the corresponding M-mode measurements at left, septal and right ventricular free wall. However, only the midpoint S and E wave PWTD signal velocities agreed numerically with those obtained by digitised M-mode velocities; S (left 6.56+/-1.80 vs. 6.54+/-1.91 cm/s N.S.); E (left 8.50+/-3.25 vs. 7.65+/-3.30 cm/s N.S.). Agreement was somewhat less satisfactory for A wave; left 7.40+/-2.13 vs. 6.23+/-2.09 cm/s p<0.05. CONCLUSION: Atrioventricular valve ring echo provides an excellent in vivo calibration model for validating tissue Doppler velocity estimates. Since the mid-point of the envelope of the tissue Doppler signal is the most closely related value to that of the digitised M-mode, it may be recommended as a convention for routine practice.

Electromechanical left ventricular resynchronisation by coronary artery bypass surgery.

OBJECTIVE: In patients with coronary artery disease (CAD), the normal electromechanical response to dobutamine stress is deranged: QRS duration lengthens rather than shortens, left ventricular asynchrony develops, post-ejection shortening appears, and total isovolumic time (the time in the cardiac cycle when the ventricle is neither ejecting nor filling) increases rather than falls, all of which blunt the normal rise in cardiac output. We aimed to study the effect of revascularisation on these stress-induced electromechanical abnormalities and their effect on peak cardiac output after coronary artery bypass grafting (CABG). METHOD: 20 unselected patients were studied before and after CABG. Long axis asynchrony was determined by (i) delay in the onset of shortening, (ii) amplitude and (iii) duration of post-ejection shortening. Total isovolumic time (in s/min), calculated as [60-(total ejection time+total filling time)] and cardiac output were measured by Doppler echocardiography. RESULTS: Before CABG: QRS duration broadened with stress (by 7+/-8 ms, P<0.01) and post-ejection shortening increased (amplitude by 1.1+/-0.7 mm, P<0.01, duration by 8+/-9 ms, P<0.01). Total isovolumic time increased (by 3+/-3 s/min, P<0.01) and cardiac output rose (by 2.8+/-1.2 l/min, P<0.01). After CABG: QRS duration shortened with stress (by 5+/-4 ms, P<0.01) post-ejection shortening decreased (amplitude and duration fell by 0.4+/-0.5 mm and 22+/-14 ms, respectively), total isovolumic time shortened (by 3+/-3 s/min) and cardiac output increased (by 5.1+/-1.8 l/min, all P<0.01). Changes in total isovolumic time and duration of post-ejection shortening with stress were independent predictors of the increase in peak cardiac output after revascularisation (total R(2)=0.69). Independent predictors of changes in total isovolumic time with stress were those in QRS duration and the duration of post-ejection shortening (total R(2)=0.75). In turn, changes in the duration of post-ejection shortening were closely associated with alterations in the delay in long axis shortening (r(2)=0.50) which correlated with changes in QRS duration (r(2)=0.59, all P<0.001). CONCLUSIONS: Revascularisation resynchronises left ventricular wall motion by restoring the normal activation response to stress, thereby reducing total isovolumic time and normalising peak cardiac output response to stress.

Importance of left ventricular activation in determining myocardial performance (Tei) index: comparison with total isovolumic time.

BACKGROUND: The Tei index is commonly used as a measure of "combined systolic and diastolic function". A sensitive and specific index of intrinsic myocardial contraction and relaxation would be independent of abnormal activation. We aimed to determine whether the Tei index fulfils this criterion in patients with normal activation or left bundle branch block (LBBB), normal or dilated left ventricular (LV) cavities, with or without coronary artery disease (CAD). METHODS: We studied 32 controls and 124 patients; 49 had CAD and normal LV size (11 LBBB), 27 had non-ischaemic dilated cardiomyopathy (DCM, 11 LBBB), and 48 had ischaemic DCM (17 LBBB). Tei index (isovolumic contraction time+isovolumic relaxation time/ejection time) and total isovolumic time (t-IVT: [60-(total ejection time+total filling time]) were measured using Doppler echocardiography. RESULTS: Tei index and t-IVT were prolonged in LBBB (by 0.6 and 9.1 s/min, P<0.001). T-IVT identified LBBB with greater predictive accuracy than Tei index (sensitivity 97% vs. 90%, specificity 93% vs. 91%, P<0.05). Tei index and t-IVT were also prolonged in DCM (by 0.2 and 3.1 s/min, both P<0.001). Although Tei index identified DCM with sensitivity 71%, this fell to 53% when LBBB was excluded (P<0.05). CAD had no effect on Tei index or t-IVT. CONCLUSIONS: The Tei index is not a measure of intrinsic myocardial systolic and diastolic function, since its main determinant is ventricular activation rather than cavity size. T-IVT, however, is more sensitive to activation, is unrelated to cavity size or CAD, and may thus be a more accurate measure of the mechanical consequences of ventricular activation in a variety of cardiac conditions.

Limitation of exercise tolerance in chronic heart failure: distinct effects of left bundle-branch block and coronary artery disease.

OBJECTIVES: The aim of this study was to identify resting measurements of left ventricular (LV) function that predict exercise capacity in dilated cardiomyopathy (DCM); in particular, the effects of left bundle branch block (LBBB), coronary artery disease (CAD), and total isovolumic time (t-IVT). BACKGROUND: The t-IVT is a major determinant of cardiac output during dobutamine stress in DCM, and is itself determined by the presence or absence of LBBB and CAD. METHODS: A total of 111 patients with DCM, 51 with CAD (29 LBBB), and 60 without CAD (30 LBBB) were studied with echocardiography and cardiopulmonary exercise testing. The t-IVT (in s/min) was measured by Doppler echocardiography, and maximal oxygen consumption (peak Vo(2)) and percentage of the normal predicted peak Vo(2) (%predicted peak Vo(2)) were obtained from exercise testing. RESULTS: Left bundle branch block reduced peak Vo(2) (by 10.5 ml.kg(-1)min(-1)) and %predicted peak Vo(2) (by 33%, both p < 0.001) compared with patients without LBBB. Coronary artery disease reduced peak Vo(2) (by 5.5 ml.kg(-1)min(-1), p < 0.001) and %predicted peak Vo(2) (by 14%, p < 0.01) compared with those without CAD (p < 0.01). The t-IVT, CAD, LBBB, and QRS duration were univariate predictors of exercise tolerance, but only t-IVT and CAD were independent predictors. The t-IVT at rest correlated with peak Vo(2) (r = -0.68) and %predicted peak Vo(2) (r = -0.74, both p < 0.001). The combination of t-IVT and CAD explained 57% (r = 0.75, p < 0.001) of the total variance in exercise capacity. CONCLUSIONS: Resting t-IVT and less prominently, CAD, are major determinants of exercise tolerance in DCM. Left bundle branch block significantly determines resting t-IVT and thus peak Vo(2). Prediction of maximum exercise capacity in DCM is therefore possible from time-domain analysis of LV function at rest.

Chronic stable ischaemia protects against myocyte damage during beating heart coronary surgery.

OBJECTIVES: Many patients with coronary artery disease demonstrate chronic resting ischaemic myocardial dysfunction. We have investigated whether this ischaemia influences the myocardial damage caused by the period of coronary occlusion involved in beating heart surgery. METHODS: Thirty-three patients with chronic stable angina and normal left ventricular ejection fraction were studied. To make our model clinically appropriate, we included patients with a wide range of ischaemic times, ages and in a subset of 10 patients a surgical preconditioning protocol. Myocyte injury was assessed from venous Troponin T release measured on days 1, 2, and 3. We used intraoperative transoesophageal M mode echocardiograms and simultaneous high-fidelity left ventricular pressure to assess whether patients were demonstrating the functional effects of ischaemia (asynchronous regional contraction with reduced mechanical function). RESULTS: Patients demonstrated the functional effects of resting ischaemia and 17 did not. Patients with resting ischaemia had lower preoperative values of regional peak power and work and all three variables increased significantly with surgery. Venous Troponin T levels at 48 and 72 h postoperatively were lower in those with preoperative resting ischaemia (median (interquartile range) 0.13 (0.08-0.20) vs 0.21 (0.13-0.69) for 48 h and 0.10 (0.08-0.19) vs 0.26 (0.12-0.51) for 72 h). Stepwise multiple linear regression of total postoperative troponin release (measured as the area under the curve of troponin release) demonstrated two independent determinants (R squared for model 0.40): longer ischaemic time, and increasing values of cycle efficiency. The surgical ischaemic preconditioning protocol and preoperative collaterals were not independent determinants. CONCLUSIONS: In patients with chronic coronary artery disease, stable preoperative ischaemia may thus represent a naturally occurring form of myocardial protection, whose presence reduces Troponin T release after beating heart surgery. This protection is different in nature from classical ischaemic preconditioning.