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).

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.

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.

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.

Evidence for rheumatic valve disease in patients with severe tricuspid regurgitation long after mitral valve surgery: the role of 3D echo reconstruction.

BACKGROUND AND AIM OF THE STUDY: Although severe tricuspid regurgitation (TR) is a well-recognized, long-term complication of rheumatic mitral valve replacement that impairs the functional results of surgery, its exact basis remains unclear and its management is unsatisfactory. The study aim was to obtain a detailed assessment of tricuspid valve morphology and function using 2D transesophageal echocardiography (TEE) with 3D reconstruction, and to determine long-term clinical outcome in patients after surgery for rheumatic mitral valve disease. METHODS: A total of 42 patients (mean age 50 +/- 10 years) was followed up; 39 patients had mitral replacement and three had valvotomy. Thirty patients had developed impaired exercise tolerance, fluid retention and echocardiographic evidence of severe TR at 8.2 +/- 2.6 years after surgery; the remainder had mild regurgitation. RESULTS: Follow up showed greater mortality in the severe TR group, with approximately 50% survival at 60 months after diagnosis compared with mild TR. None of the patients with severe TR had a dysfunctional mitral prosthesis. In these patients, transthoracic echo-Doppler showed enlarged right atrium and right ventricle, a mean transtricuspid retrograde pressure drop of 15 +/- 4 mmHg and apparently normal leaflet anatomy. Twenty patients (15 with severe TR) underwent a TEE and 3D reconstruction study for further evaluation. Abnormal leaflet anatomy was demonstrated in all patients with severe TR, with restricted leaflet motion in 10, leaflet shortening and thickening in the remainder, and dilatation of tricuspid valve annular insertion suggestive of rheumatic involvement. Although diastolic transtricuspid velocities were increased (peak flow 0.8 +/- 0.1 m/s) in these patients due to increased stroke volume, significant tricuspid stenosis was present in only two cases (mean gradient 4 and 3 mmHg respectively). Histopathology confirmed the presence of leaflet vascularization and extensive fibrosis in two patients who underwent tricuspid valve replacement. CONCLUSION: Rheumatic leaflet involvement contributes to severe TR occurring long after mitral valve replacement, though overt stenosis is uncommon. Knowledge of the structural basis of this condition may thus improve its long-term management, possibly with early tricuspid valve repair.

Differentiation of ischemic from nonischemic cardiomyopathy during dobutamine stress by left ventricular long-axis function: additional effect of left bundle-branch block.

BACKGROUND: Resting regional wall-motion abnormalities do not reliably distinguish ischemic from nonischemic cardiomyopathy. Dobutamine stress echocardiography with use of the wall-motion score index (WMSI) identifies coronary artery disease (CAD) in dilated cardiomyopathy (DCM), but the technique is subjective and further complicated by left bundle-branch block (LBBB). Long-axis motion is sensitive to ischemia and can be assessed quantitatively. We aimed to compare long-axis function with WMSI for detecting CAD in DCM with or without LBBB. METHODS AND RESULTS: Seventy-three patients with DCM, 48 with CAD (16 with LBBB), and 25 without CAD (10 with LBBB) were studied. Long-axis M-mode, pulsed-wave tissue Doppler echograms (lateral, septal, and posterior walls), and WMSI were assessed at rest and at peak dobutamine stress. Failure to increase systolic amplitude (total amplitude minus postejection shortening) by 2 mm or early diastolic velocity by 1.1 cm/s was the best discriminator for CAD (systolic amplitude, sensitivity 85%, specificity 86%; lengthening velocity, 71% and 94%, respectively; P=NS). Both had greater predictive accuracy than did WMSI (sensitivity 67%, specificity 76%; P<0.001). The predictive accuracy of changes in septal long-axis function was similar to those of average long-axis function (systolic amplitude cutoff=1.5 mm, lengthening velocity cutoff=1.5 cm/s). However in LBBB, systolic amplitude proved to be the only significant discriminator for CAD, with sensitivity and specificity reaching 94% and 100%, respectively (P<0.01 versus early diastolic lengthening velocity). CONCLUSIONS: Quantified stress long-axis function identifies CAD in DCM with greater sensitivity and specificity than does standard WMSI, particularly in the presence of LBBB.

Limitation of cardiac output by total isovolumic time during pharmacologic stress in patients with dilated cardiomyopathy: activation-mediated effects of left bundle branch block and coronary artery disease.

OBJECTIVES: We sought to separate the effects of associated left bundle branch block (LBBB) and coronary artery disease (CAD) on peak cardiac output (CO) during dobutamine stress in patients with dilated cardiomyopathy (DCM). BACKGROUND: The mechanisms limiting CO during stress in patients with DCM are unclear. Both LBBB and CAD may do so by prolonging the total isovolumic time (t-IVT). METHODS: A total of 59 patients with DCM-34 with CAD (20 normal activation [NA], 14 LBBB) and 25 without CAD (15 NA, 10 LBBB)-were studied. The total IVT (s/min; calculated as: 60 - [total ejection time + total filling time] ) and CO were measured by Doppler echocardiography. RESULTS: At rest, t-IVT was 8 s/min longer with LBBB (p < 0.001), was unaffected by CAD, and did not correlate with rest CO. During stress, CO correlated with t-IVT (r = -0.73, p < 0.001) in all four patient groups. In the absence of CAD, t-IVT became shortened (NA by 7 +/- 3 s/min; LBBB by 9 +/- 4 s/min) and correlated with a fall in the QRS duration (NA: r = 0.87; LBBB: r = 0.91), and CO increased with stress (NA by 4.7 +/- 2.7 l/min; LBBB by 4.0 +/- 2.3 l/min; all p < 0.001). With CAD, t-IVT did not shorten normally with stress. Instead, t-IVT was 5.6 s/min longer and CO was 3.3 l/min lower than in those without CAD (both p < 0.001), and t-IVT did not correlate with the QRS duration. CONCLUSIONS: In patients with DCM, t-IVT during pharmacologic stress depends on changes in ventricular activation induced by LBBB or CAD and is, by itself, a major determinant of peak CO during stress.

Septal q waves as an indicator of risk of mortality in elderly patients with chronic heart failure.

BACKGROUND: The absence of electrocardiographic septal q wave is a recognized marker of left ventricular disease. We aimed to investigate the prognostic significance of absent septal q waves in elderly (age >65 years) patients with chronic heart failure. METHODS: A total of 110 patients (mean age 73 +/- 4 years) with New York Heart Association functional class II to IV and left ventricular ejection fraction of <45% were enrolled in the study. Standard 12-lead electrocardiograms were critically analyzed for the presence or absence of septal q waves in leads I, aVL, V5, and V6. Patient survival was determined from hospital and general practitioner records and National Statistics Registry at a mean follow-up of 4 years. RESULTS: Septal q waves were absent in 71 and present in 39 patients. The overall mortality rate was 47% (43 patients). The incidence of death was 49% (36 patients) in the group with no septal q waves and 18% (7 patients) in those who demonstrated septal q waves. On univariate analysis by Cox proportional hazard method, absence of septal q waves was found to be a strong marker of poor prognosis in CHF (P =.003, hazard ratio 1.40, 95% CI 1.10-1.67). Kaplan-Meier survival curves showed a significant difference in survival independent of age, New York Heart Association functional class, peak VO2, and QRS duration between these 2 groups. CONCLUSIONS: Absence of the normal septal q wave on 12-lead electrocardiography, which may indicate structural heart disease and myocardial fibrosis, is an independent predictor of poor prognosis in elderly patients with CHF.

The effect of the localization of Q wave myocardial infarction on ventricular electromechanics.

BACKGROUND: The exact location of a Q wave myocardial infarction has an important effect on overall left ventricular function. OBJECTIVES: To assess the effect of localization of Q wave infarction on left ventricular minor and long axis function, with particular reference to electromechanical disturbances. METHODS: We studied 72 patients with Q wave myocardial infarction; 35 anterior, age 61+/-15 years and 37 inferior, age 62+/-12 years. ECG intervals were automatically measured by Hewlett-Packard Pagewriter and LV dimension and filling velocities studied by transthoracic echocardiography and simultaneous phonocardiogram. Findings were compared with 21 controls of similar age. RESULTS: Heart rate and all ECG intervals were similar in the two patient groups and controls. QRS axis was more to the left in patients with inferior MI. Normal septal q wave was absent in lead V5 and V6 in 33/35 (94%) patients with anterior MI and in only 3/37 (8%) with inferior MI, p<0.001. LV minor axis dimensions were enlarged vs. normal (p<0.001) in the two patient groups and to a greater extent in anterior MI compared with inferior MI, p<0.05. Isovolumic relaxation time was prolonged only in-patients with an inferior MI, p<0.01. Long axis amplitude was globally reduced (p<0.001) in the two patient groups as were shortening and lengthening velocities (p<0.001). The onset of septal long axis shortening with respect to the q wave was delayed by 30 and 40 ms in inferior MI and anterior MI and that of lengthening with respect to A2 by 20 and 30 ms, respectively, compared to normal (p<0.001 for both). Post ejection shortening was localized to the septal long axis in 32/35 patients with anterior MI but was generalized involving all three LV long axes in inferior MI, p<0.001. Transmitral Doppler flow velocities and the frequency of mild mitral regurgitation were similar in the two groups. CONCLUSION: These results confirm a close association between anterior Q wave infarction, septal incoordination and absent septal q waves. The global incoordinate long axis behaviour in inferior Q wave MI may be due to significant papillary muscle dysfunction, and results in significant shape change in early diastole. This disturbance in electromechanical behaviour might play an important role in the differing outcomes between the two different sites of myocardial infarction.

Effect of atrial flutter on exercise tolerance in patients with grown-up congenital heart (GUCH).

OBJECTIVES: To assess the effect of atrial flutter (AFL) on exercise tolerance in patients with grown-up congenital heart (GUCH), exercise tests with modified Bruce protocol were performed in 20 patients aged 21 to 62 years with GUCH (11 females, 9 males) during symptomatic AFL and again 24 to 48 hours after DC conversion to sinus rhythm (SR). At the same time, cardiac function was assessed by means of transthoracic Doppler echocardiography. RESULTS: Mean exercise duration was significantly less during AFL (6.4 +/- 4.1 min) versus SR (10.9 +/- 3.7 min) (P <.001). Heart rate was faster at rest and peak exercise while in AFL (106 +/- 21 beats/min vs 77 +/- 14 beats/min, P <.001, and 157 +/- 31 beats/min vs 129 +/- 24 beats/min, P <.01, respectively). Systolic blood pressure was lower at peak exercise with AFL (112 +/- 25 mm Hg vs 137 +/- 24 mm Hg, P <.001), as was mean blood pressure increase (5.3 +/- 24.3 mm Hg vs 22.6 +/- 15.8 mm Hg) compared with SR (P <.01). Four of the 6 patients after Fontan surgery had a decrease of 16 mm Hg in systolic blood pressure at peak exercise when in AFL. The reasons for exercise termination during AFL were mainly breathlessness, chest pain, or presyncope, whereas in SR it was caused by fatigue. Echocardiography during AFL showed shorter isovolumic relaxation time (40 +/- 20 ms) compared with SR (50 +/- 20 ms) (P <.05). Ventricular long-axis excursion was reduced (left 1.0 +/- 0.3 cm vs 1.2 +/- 0.4 cm, septal 0.5 +/- 0.2 cm vs 0.7 +/- 0.3 cm, and right 0.7 +/- 0.2 cm vs 0.9 +/- 0.4 cm respectively, P <.001 for all), as were peak pulmonary and aortic flow velocities (85 +/- 30 cm/s vs 105 +/- 50 cm/s, P <.001, and 137 +/- 118 cm/s vs 143 +/- 114 cm/s, P <.02) compared with sinus rhythm. There was a close correlation between exercise duration and blood pressure increase (r = 0.6), left-sided long-axis excursion and blood pressure increase (r = 0.57), and between aortic flow velocity and right-sided long-axis excursion (r = 0.71). CONCLUSIONS: Atrial flutter causes dramatic reduction in exercise tolerance in patients with GUCH, and the combination of fast heart rate and hypotension may contribute to the development of presyncope, particularly in those with Fontan surgery. Marked improvement in effort tolerance and cardiac dynamics occurs after regaining SR. Thus, improving the quality of life in patients with GUCH requires maintaining SR.