Derek G. Gibson

Natural history of abnormal conduction and its relation to prognosis in patients with dilated cardiomyopathy

To investigate the natural history of disturbances in ventricular activation, atrioventricular conduction, and ventricular cavity size, we retrospectively studied 58 patients from a total of 296 patients with dilated cardiomyopathy seen within 4 years. A total of 309 computerised electrocardiograms (ECGs) and 135 M-mode echocardiograms were analysed. In the majority of the patients, PR interval, QRS duration and QT interval prolonged progressively, though heart rate changed little. Their increase was much more striking in patients who died (n = 10) or had a pacemaker inserted (n = 9), compared to that in the clinically stable patients, though at entry all these values, as well as age and left ventricular cavity size, were similar. There were no significant differences between patients who died and those with a pacemaker inserted, except for QRS axis, which had shifted rightwards in 8 out of 10 who died, but only in 3 of 9 who subsequently had a pacemaker inserted and 14 of the 29 stable patients. A QRS duration over 160 ms was found in 8 out of the 10 patients who died, 6 of 9 who had a pacemaker and only in 5 out of the 39 stable patients (P < 0.001). The sum of PR interval and QRS duration over 375 ms was not found in any stable patient but was present in 6 of the 7 patients who were in sinus rhythm and died (P < 0.001). Left ventricular cavity size also increased with time, but did not correlate significantly with ECG progression, nor did it identify patients who subsequently died. Thus, a combination of increasing PR interval and QRS duration, particularly along with rightwards shift of QRS axis, appears to be a marker of high risk in patients with dilated cardiomyopathy.

Effects of Valve Substitute on Changes in Left Ventricular Function and Hypertrophy After Aortic Valve Replacement

BACKGROUND Residual left ventricular hypertrophy adversely affects long-term outcome after aortic valve replacement. A stentless biological valve in the aortic position has been shown to offer a better hemodynamic profile than a stented one. However, it remains to be defined whether this difference is translated into inter-mediate-term effects on left ventricular structure and function. METHODS One hundred thirty-seven patients receiving single aortic valve replacement (52 with concomitant coronary artery bypass graft) were enrolled in this study. Ninety-eight were men, and the mean age was 68 years (range, 55 to 90 years). Of the 137 patients, 39 had an aortic homograft, 72 a Toronto stentless porcine valve, and 26 had a stented porcine or bileaflet mechanical valve, with mean valve size of 25 +/- 2.5 mm (mean +/- standard deviation). Left ventricular muscle mass and function were assessed by M-mode echocardiography performed before and 0.5, 6, 12, 24, and 36 months after operation, and recorded on paper for off-line digitizing. Peak valve prosthesis pressure gradients were quantified by continuous wave Doppler. RESULTS A total of 330 echocardiograms obtained during this study were adequate for computer digitizing. Clinical data, preoperative left ventricular function, and hypertrophy were similar between the three groups. Significant improvement in left ventricular function and major regression of left ventricular hypertrophy had occurred in the entire population by 6 months after operation. Multivariate analysis of variance showed that patients with previous aortic regurgitation had a larger left ventricular cavity size (p < 0.001) and greater mass index (p = 0.001) postoperatively than those with previous aortic stenosis. In addition, peak valvular gradient was lower (p < 0.001), mass index less (p < 0.001), and left ventricular function more normal both systolic, by a greater peak velocity of dimension shortening (p = 0.05) and wall thickening (p = 0.002), and diastolic, by a greater peak velocity of dimension lengthening (p = 0.046), with an aortic homograft or stentless porcine valve compared with a mechanical or stented biological valve. There was no significant difference in peak valve gradient, left ventricular mass index, or function between the aortic homograft and the stentless porcine valve. Age, sex, and concomitant coronary artery bypass graft, as well as aortic cross-clamp time, cardioplegia method, and valve size all proved to be insignificant determinants of postoperative left ventricular hypertrophy or function. CONCLUSIONS In the first 2 years after implantation, the superior hemodynamic performance of aortic homograft and stentless porcine valve appears to result in more extensive regression of ventricular hypertrophy and greater improvement of left ventricular function than occurs with a mechanical or stented biological valve. These findings encourage the use of a stentless biological valve in older patients requiring aortic valve replacement, and a larger scale long-term randomized study of stentless versus stented biological valve or mechanical valve seems warranted.

Long axis function in disease

Although longitudinally directed fibres—situated mainly in the subepicardium and subendocardium regions of the left and right ventricular free walls and the papillary muscles—comprise only a small proportion of the total ventricular myocardial mass, they play a major role in the maintenance of normal ejection fraction and in determining atrioventricular interactions.1 Not surprisingly, therefore, loss of longitudinal fibre function leads to characteristic disturbances. Longitudinal function is always reduced when ventricular cavity size is increased, in addition ejection fraction is reduced and may be absent.2 3 This relation is consistent enough for long axis amplitude, or its equivalent, the amplitude of atrioventricular ring motion, to be used as an index of ejection fraction.4It applies not only to the left ventricle, where it can be shown to relate to prognosis but also to the right, where it provides a simple method of assessing right ventricular function.5 When overall long axis amplitude is low, peak shortening and lengthening rates are reduced. In restrictive left ventricular disease, long axis amplitude is low even when cavity size is normal at end diastole, although the effects of this reduction are apparent in a reduced amplitude of wall thickening and thus of shortening fraction.6 After mitral valve replacement, long axis amplitude is strikingly reduced; this does not occur with mitral valve repair or mild mitral stenosis,7 nor is it a consistent effect of cardiopulmonary bypass done for other reasons, and so is likely to be the result of loss of papillary muscle function. Although shortening fraction is frequently normal in such patients, normal wall thickening is associated with an exaggerated amplitude of epicardial motion, possibly to compensate for loss of the component owing to long axis shortening. Regional reduction in the extent and velocity of long axis shortening is common after …

Analysis of left ventricular wall movement during isovolumic relaxation and its relation to coronary artery disease.

Left ventricular angiograms of 60 patients with ischaemic heart disease and 10 normal subjects were digitized frame by frame in order to study abnormalities of wall movement during the period of isovolumic relaxation. Plots were made of regional wall movement around the cavity throughout the cardiac cycle. In normal subjects 1-5 to 3-0 mm of symmetrical outward wall movement occurred during isovolumic relaxation, associated with an apparent increase of left ventricular volume of 10 +/- 4 per cent. The corresponding peak velocities of wall movement were 4-3 to 5-7 cm/s, significantly less than those recorded in the same region of the cavity after mitral valve opening. In patients with ischaemic heart disease, the following abnormalities were encountered: (1) Abnormal inward movement, which, in single coronary artery disease, occurred in the area supplied by the affected vessel. (2) Abnormal outward movement of more than 6 mm in non-affected areas which appeared to be a compensatory phenomenon. (3) An abnormal cavity shape change towards a more circular configuration before mitral valve opening. (4) Reduced peak rates of wall movement in affected areas during systole and filling. It is concluded that such inward wall movement during isovolumic relaxation is abnormal and a sign of local ischaemia whose presence has significant effects on overall left ventricular function in both systole and diastole.

Normal long axis function

Ever since the time of Vesalius and Harvey,1 it has been recognised that the fall in cavity volume with left ventricular systole involves longitudinal as well as circumferential shortening, although the latter plays the dominant role. This asymmetry is reflected in myocardial structure—most of the left ventricular fibres are arranged circumferentially, particularly in the mid-wall and the base of the ventricle, however, with the progressive change in fibre angle across the wall, longitudinally directed fibres are found in the subendocardial and subepicardial free wall (fig 1) as well as in the papillary muscles.2 Figure 1 Diagram showing dissection in a normal left ventricular myocardium with the longitudinal fibres running between the apex and mitral ring and occupying the subendocardial and subepicardial layers. In view of the preponderance of circumferential fibres, it seems logical to deduce underlying myocardial function from the extent and velocity of their shortening3; however, the picture of the underlying function reached from observing changes in left ventricular minor axis is at first sight surprising. Normal dimensions fall by 25–40% during ejection, while the normally loaded sarcomere shortens by only 10–12%.4 Furthermore, this remarkable fall in minor axis is the result of thickening of the posterior wall to an extent much greater than would be expected from simultaneous inward movement of the epicardium.5 This apparent increase in myocardial mass that must underlie the observed extent of thickening can only be explained by concurrent shortening, and thus transverse thickening, of the longitudinally directed fibres. Without this longitudinal component, normal sarcomere shortening would lead to a shortening fraction of 12% and an ejection fraction of less than 30%. Thus, even normal changes in minor axis with ejection can be explained only on the basis of the combined action of the circumferential and longitudinal fibres.6 This …

Enhanced deposition of predominantly type I collagen in myocardial disease

The myocardium consists of a muscle fibre array surrounded and interspersed by a network of connective tissue, principally collagen, which maintains the functional integrity of the heart. Changes in collagen composition may therefore contribute to altered ventricular function. Collagen composition was examined in cardiac tissue from 15 patients undergoing orthotopic cardiac transplantation. Of these, 10 had severely impaired left ventricular function due to coronary artery disease. The remaining five had dilated cardiomyopathy. Normal heart tissue was taken at autopsy from 25 patients who died of causes unrelated to cardiovascular disease. Left ventricular collagen concentration, estimated from hydroxyproline levels, increased from 48.6 +/- 4.1 mg/g dry weight of tissue in the control group to 95.3 +/- 9.7 mg/g (P less than 0.01) in patients with dilated cardiomyopathy and to 63.5 +/- 9.8 mg/g in the coronary artery disease group. This increase was attributable to an increase in absolute concentrations of both type I and III collagen, determined by separation of cyanogen bromide peptides by sodium dodecyl sulphate polyacrylamide gel electrophoresis. However, there was a significant decrease in the proportion of type III collagen (compared with type I plus III) from 41.8 +/- 1.1% in controls, to 34.6 +/- 1.5% (P less than 0.01) in the coronary artery disease group and 35.8 +/- 2.8% (P less than 0.05) in the dilated cardiomyopathy group. These results suggest that excessive collagen production, with a preponderance of type I, occurs in these forms of myocardial disease, indicative of a remodelling of the collagen matrix, which, by increasing passive myocardial stiffness may contribute to impaired heart function seen in these groups of 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.

What stops the flow of blood from the heart

SummaryThe determinants of aortic pressure and flow are generally studied using impedance methods, the results of which indicate that reflected waves are important, particularly during aortic flow deceleration. An alternative analysis of measured aortic pressure and velocity, using the method of characteristics to calculate the energy flux per unit area of the waves, suggests a different conclusion. We suggest that aortic deceleration is caused by a discrete expansion wave propagating from the left ventricle, and that energy thus recovered by the ventricle may be coupled to early filling of the ventricle.

Nature of ventricular activation in patients with dilated cardiomyopathy: evidence for bilateral bundle branch block.

OBJECTIVE--To investigate the nature of ventricular activation and its relation with mechanical events in patients with dilated cardiomyopathy. STUDY DESIGN--Retrospective and prospective study with 12 lead electrocardiograms, signal averaged electrocardiograms, and M mode and Doppler echocardiograms. SETTING--Tertiary cardiac referral centre. PATIENTS--77 patients (mean (SD) age 59(13)) with dilated cardiomyopathy, four after aortic valve replacement and three after coronary bypass surgery, and six patients with a normal sized left ventricle and complete right bundle branch block were studied. 15 normal subjects (age 45(20)) were used as controls. RESULTS--In patients with dilated cardiomyopathy, QRS duration was longer (127(25) ms v 90(10), P < 0.05) than normal and was normally distributed (r = 0.991, P < 0.01) on a normal probability plot. 20 had classic left bundle branch block, 29 intraventricular conduction delay, four right bundle branch block, and one bifascicular block. The PR interval was prolonged (185(30) ms v 150(15), P < 0.05). Electromechanical delay, Q to the onset of thickening of the interventricular septum as seen on the transverse M mode echocardiogram, was 75(15) ms in controls, but reduced to 43(15) ms in the patients (P < 0.01). Q to the onset of mitral regurgitation was also short (50(15)) ms, and correlated inversely with PR interval (r = -0.67, n = 73, P < 0.01). Early potentials (< 40 microV) were recorded on the signal averaged electrocardiogram in 33 representative patients and in all controls. Their overall duration was 30(12) ms in the patients, much longer than normal (12(7), P < 0.01)). Early potential time correlated positively with PR interval (r = 0.75, P < 0.01) and QRS duration (r = 0.60, P < 0.01) on a 12 lead electrocardiogram, and negatively with apparent electromechanical delay (r = -0.71, P < 0.01, n = 33), but not with true electromechanical delay (73(15)ms) or true PR interval (163(30)ms), calculated by correcting apparent values for early potential. The onset of left ventricular free wall motion was delayed with respect to the septum beyond 95% of the upper normal limit in all the patients with classic left bundle branch block and intraventricular conduction defect. Motion in the right ventricular free wall was delayed in 13 of 20 patients with left bundle branch block and 24 of 29 with intraventricular conduction defect by 65(20) ms, similar to that (75(10) ms) in patients with right bundle branch block. CONCLUSION--In most patients with dilated cardiomyopathy and an electrocardiographic pattern of left bundle branch block or intraventricular block, the onset of mechanical systole is strikingly and symmetrically delayed in both ventricles, compatible with bilateral bundle branch block. Complete atrioventricular block does not occur. The ventricle is activated through the upper septum and this activation is detectable only by signal averaged electrocardiography. The anatomical substrates for this abnormal activation could be the high connections described by Mahaim and Winston.

Incremental changes in QRS duration in serial ECGs over time identify high risk elderly patients with heart failure

Aims: To investigate the hypothesis that changes in the ECG over time may be an important and readily available marker of prognostic value in patients with heart failure. Methods: 112 elderly patients (81 men) with stable heart failure, a mean (SD) age of 73.3 (4.4) years, left ventricular ejection fraction 38 (17)%, and peak oxygen consumption 15.1 (4.7) ml/kg/min had ECG measurements on two occasions a minimum of 12 (5) months apart. Results: During the subsequent follow up period (mean 27 (17) months) 45 patients died. QRS duration (p = 0.001) and heart rate (p = 0.03) at baseline were found by Cox proportional hazard method analysis to predict adverse outcomes in these patients. Of the changes in ECG parameters between the first and second visit, broadening of QRS duration (p = 0.001) predicted mortality. On Kaplan-Meier survival analysis, patients with < 5% change in QRS duration had fewer end points than patients with 5–20% change. A > 20% increase in QRS duration was associated with the worst prognosis. Progressive prolongation of QRS duration correlated closely with deterioration of LV systolic and diastolic function. Conclusion: A single measurement of QRS duration has significant prognostic value in elderly patients with heart failure and the increase in QRS duration over time is an even better predictor of adverse out comes.