QT interval in twins.

QT interval has been determined in 103 monozygotic (MZ) and 198 dizygotic (DZ) female twins. Mean values of corrected QT (QTc) were almost identical for both groups at 413 ms (MZ) and 412 ms (DZ). There was a significant age and environmental effect on QT interval. Heritability explained about 25% of the variation in QT. Further research will show whether any of the genes known to cause Long QT syndrome have any effect on QT interval at the sub-clinical level. Journal of Human Hypertension (2000) 14, 389-390

Exercise-induced T-wave alternans as a marker of high risk in patients with hypertrophic cardiomyopathy.

Microvolt-level T-wave alternans (alternating morphology from beat to beat) during atrial pacing and exercise may predict ventricular tachycardia (VT) and fibrillation (VF) in ischemic heart disease. We tested whether such alternans during exercise could identify high-risk patients with hypertrophic cardiomyopathy (HCM). We studied 14 HCM patients and 9 normal control subjects for T-wave alternans u sing the CH2000 system with 7 multisegment electrodes in a Frank orthogonal (XYZ) configuration. Bicycle ergometer exercise was used to increase the heart rate (HR) to 95-110 beats/min. Seven patients were at high risk for ventricular arrhythmias (1 with sustained VT, 3 with abnormal paced ventricular electrograms as seen in VF survivors, and 3 with nonsustained VT and/or an adverse family history), and the other 7 were at low risk. T-wave alternans was present if alternans > 1.9 microV was consistently present with the HR in excess of a patient-specific HR threshold. Alternans was found in 5 of 7 high-risk patients (71%) vs none of 7 low-risk patients or 9 control subjects (p < 0.025 and p < 0.01, respectively). Notably, all 4 patients with sustained VT or abnormal ventricular electrograms showed alternans. Thus, high-risk patients with HCM often show T-wave alternans. Microvolt-level alternans during exercise may be a useful marker for ventricular arrhythmic risk in patients with HCM.

DDD pacing in hypertrophic cardiomyopathy: a multicentre clinical experience.

BACKGROUND: DDD pacing has been advocated as an effective treatment for drug refractory obstructive hypertrophic cardiomyopathy. This study reports the outcome of pacing in 56 patients with refractory symptoms referred to four tertiary centres. METHODS: Core data on symptoms, drug burden, and left ventricular outflow tract gradient were recorded. Patients underwent a temporary pacing study with optimisation of the atrioventricular (AV) delay for greatest gradient reduction without haemodynamic compromise. Patients were assessed after implantation in terms of changes in symptoms, drug load, and outflow tract gradient. RESULTS: 56 patients underwent pacing assessment. The mean (SD) left ventricular outflow tract gradient before pacing was 78 (31) mm Hg. At temporary study the mean (SD) left ventricular outflow tract gradient was 38 (24) mm Hg with a median (range) optimised sensed AV delay of 65 (25-125) ms. Fifty three patients were implanted and followed up for a mean (SD) of 11 (11) months. The median (range) programmed sensed AV delay was 60 (31-200) ms. Left ventricular outflow tract gradient at follow up was 36 (25) mm Hg. Forty four patients had improved functional class. Although a correlation (r = 0.69) was shown between acute and chronic left ventricular outflow tract gradient reduction, there was no correlation between magnitude of gradient reduction and functional improvement, and no appreciable change in pharmacological burden. CONCLUSION: This series confirms symptomatic improvement after DDD pacing in hypertrophic cardiomyopathy. There remains, however, a discrepancy between perceived symptomatic benefit and modest objective improvement. Furthermore, the optimal outcome has been achieved only with continued pharmacological treatment. Current methods of temporary evaluation do not predict functional outcome which seems to be independent of the magnitude of gradient reduction.

Primary ventricular fibrillation is associated with increased paced right ventricular electrogram fractionation.

BACKGROUND: The mechanisms of spontaneous ventricular fibrillation (primary VF) in patients without structural heart disease are obscure. A new technique has shown that in patients with hypertrophic cardiomyopathy conduction of fractionated ventricular paced beats, recorded at several right ventricular sites, is prolonged in individuals who have suffered a VF arrest, and this may reveal one component of a reentrant substrate. Patients with primary VF were studied with the same methods to determine whether similar abnormalities are present in this group. METHODS AND RESULTS: Nine patients with primary VF were studied by pacing one right ventricular (RV) site by use of a constant drive train with an extrastimulus inserted every third beat and reducing the extrastimulus coupling interval (S1S2 interval) by 1 ms on each occasion while recording at three other sites. The delay of each fractionated potential in the high-pass-filtered electrograms in response to the extrastimulus was determined and used to form conduction curves of delay versus the S1S2 interval. These curves were repeated by pacing each RV site in turn and recording from the other three sites. The curves were characterized by determining the S1S2 interval at which electrogram components increased in delay by 0.75 ms/20 ms reduction in S1S2 interval and the increase in electrogram duration between a coupling interval of 350 ms and 1 ms above refractoriness. Seven control patients were studied using the same method. The mean increase in electrogram duration in VF patients was 13 ms (range, 3 to 23 ms) compared with 4 ms (range, -2 to 14 ms) in unaffected control patients. The extrastimulus coupling interval at which delay increased was 318 ms (range, 293 to 334 ms) in VF patients and 274 ms (range, 265 to 284 ms) in control patients (P < .01). There was no difference between the number of fractionated potentials in VF patients and control patients. CONCLUSIONS: In primary VF patients, the individual potentials within fractionated electrograms have increased delays when compared with control patients. This may identify one component of a reentrant arrhythmic substrate.

The significance of paced electrogram fractionation in hypertrophic cardiomyopathy. A prospective study.

BACKGROUND: Increased duration of paced right ventricular (RV) electrograms in hypertrophic cardiomyopathy has been shown in 37 patients to correlate with the risk of ventricular fibrillation (VF). The changes in electrogram duration with pacing stimulus prematurity discriminated patients into three groups: VF survivors, an intermediate group with either non-sustained ventricular tachycardia (NSVT) on ambulatory monitoring or a family history of sudden death (FHSD), and those with none of these risk factors (noRF) for sudden death (SD). The consistency of these original groups has been tested prospectively in a further 64 patients. METHODS AND RESULTS: Of 64 patients with hypertrophic cardiomyopathy, 3 had documented VF, 1 had witnessed SD and is assumed to have had VF, 25 had NSVT, 21 had FHSD, and 14 had noRF. Nineteen patients had syncope. They were studied by pacing one RV site with a decremental sequence and recording high-pass filtered electrograms from three other RV sites. The delay of each fractionated potential in the electrogram was determined relative to a pacing stimulus of increasing prematurity. These measurements were repeated by pacing each ventricular site in turn. The electrograms were characterized by two parameters: the extrastimulus coupling interval (S1S2) at which delay increased by more than 0.75 ms/20 ms decrease in S1S2 interval and the change in electrogram duration between an S1S2 of 350 ms and ventricular effective refractory period. The 4 VF patients had a mean increase in electrogram duration of 16.1 ms and an increase in delay at a mean S1S2 of 368 ms. Three VF patients were within the original VF group, while only 6 of 60 non-VF patients were within this group, discriminating between VF patients and the remainder (P < .007). The 14 noRF patients had a mean change in electrogram duration of 4.5 ms and an increase in delay at a mean S1S2 of 301 ms. Eleven patients were within the original noRF group, and only 8 of the remaining 50 patients also were within the noRF group, discriminating between the noRF patients and the remainder (P < .0005). Most of the NSVT and FHSD patients were between the original VF and noRF groups, with 5 of 25 NSVT and 1 of 31 FHSD patients in the original VF group. There was no relation between syncope and electrophysiological characteristics. Programmed electrical stimulation (PES) was performed in the first 15 patients of this study. Of the total 52 patients from the original and current studies, PES identified 2 out of 6 VF patients, and there was no correlation between VF inducibility and intraventricular conduction delay. CONCLUSIONS: These data are consistent with the original VF and noRF groups. Most patients with FHSD or NSVT were between these groups. Pooled data from the original and current groups (n = 101) allow definition of a new VF group, which includes all patients with VF (n = 9), 8 of 30 patients with VT, and 3 of 31 patients with FHSD. This new group may be used as a criterion for implantable cardioverter-defibrillator implantation in a prospective trial of the technique for the prediction of SD.

The arrhythmogenic substrate--diagnostic and therapeutic implications: hypertrophic cardiomyopathy.

Hypertropic cardiomyopathy provides an important model for the study of mechanisms of sudden death. Initiating factors for sudden cardiac death may include sinus tachycardia and paroxysmal supraventricular arrhythmias. The haemodynamic effects of such triggers may be modulated depending on the patients exercise haemodynamics, peripheral vasomotor control and autonomic function. Myocardial disarray provides the underlying histological substrate for the lethal ventricular arrhythmias that represent the final common pathway. Attempts at individual risk stratification for sudden cardiac death using conventional risk factors and non-invasive techniques such as Holter monitoring identify a large group of patients, many of whom will not experience sudden cardiac death. Conventional electrophysiological methods such as programmed ventricular stimulation do not add to risk stratification inducing a variety of non-sustained or non-specific ventricular arrhythmias. A novel electrophysiological technique described in this article offers more promise in this regard.

Ventricular fibrillation in hypertrophic cardiomyopathy is associated with increased fractionation of paced right ventricular electrograms.

BACKGROUND: Intraventricular conduction in hypertrophic cardiomyopathy (HCM) has been characterized to test the hypothesis that myofibrillar disarray will cause dispersion of activation throughout the ventricular myocardium. METHODS AND RESULTS: Of 37 patients with HCM, four had spontaneous ventricular fibrillation (VF), five had nonsustained ventricular tachycardia (VT), 13 had no risk factors, and 15 had a family history of sudden death. These patients and four controls were studied by pacing one site in the right ventricle and recording electrograms from three other right ventricular sites. These electrograms were high-pass filtered to emphasize small deflections due to activation of small bundles of myocytes close to the electrode. Intraventricular conduction curves were obtained with S1S2 coupling intervals decreasing in 1-msec steps from 479 msec to ventricular effective refractory period (VERP). These curves were repeated by pacing each RV site in turn and were characterized by two parameters: the point at which latency increased by 0.75 msec/20 msec reduction of the S1S2 coupling interval and an increase in electrogram duration between an S1S2 of 350 msec and VERP. Patients with VF, VT, and family history of sudden death had a mean increase in electrogram duration of 12.8 (2.9-32.3) msec versus 4.6 (-4.2 to 14.0) msec in low-risk patients and controls. Electrogram latency increased at an S1S2 of 363 msec in the VF group (342-386), 269 msec in the controls (266-279), and 326 msec in the non-VF group (260-399). Discriminant analysis separated VF patients from the remainder (p less than 0.0001) and VF, VT, and family history of sudden death patients from the low-risk and control groups (p less than 10(-6)). CONCLUSIONS: Patients with HCM who are at risk of sudden death have increased dispersion and inhomogeneity of intraventricular conduction, and this may create the conditions for reentry and arrhythmogenesis.

Geometrically accurate activation mapping of the atrioventricular node region during surgery.

A novel method has been developed to map activation in the triangle of Koch during surgery for cardiac arrhythmias and relate the map to anatomic landmarks. It uses a hand-held electrode mounted in a freely moving linkage that has three degrees of mechanical freedom. The movements of the linkage are sensed by a computer that continuously calculates the coordinates of the electrode. The surgeon clamps the device over the triangle of Koch after the right atrium has been opened and uses the electrode to trace the anatomic landmarks of the region that are displayed on the computer screen. The position of the electrode is displayed continuously relative to these landmarks and electrograms are recorded at known positions to generate a map. The activation sequences during sinus rhythm, atrioventricular node reentrant tachycardia, "common" and "uncommon" atrial flutter, long RP' tachycardia and retrograde conduction through paranodal pathways are presented. It is concluded that 1) the high spatial resolution reveals physiologically important areas in the maps that are 8 mm long and 3 mm wide and that these areas can be related to specific anatomic landmarks; 2) there are complex electrograms in the region that may reflect the activation of different myocardial layers; and 3) there are marked changes in conduction velocity and direction within the region.

Geometrically accurate transaortic mapping of left ventricular endocardial activation during surgery.

A device was developed for mapping left ventricular endocardial activation through the aortic valve during surgery. It uses an exploring electrode at the tip of a hand-held probe that is mounted on a mechanical arm with six joints whose movements are digitized by a computer while the position of the probe tip is calculated continuously. The probe is inserted by the surgeon into the left ventricle retrogradely through the aortic valve after the patient is on total cardiopulmonary bypass, the aorta has been opened and the coronary arteries cannulated. The electrode position relative to the aortic valve and left ventricular apex is displayed continuously on a computer screen. When electrograms are recorded from the probe, their positions are displayed on the screen relative to a stylized grid of the left ventricular endocardial surface and are color-coded to indicate the activation sequence. In a patient with nonischemic ventricular tachycardia, the arrhythmia was successfully mapped and cryoablated with use of the device. The device will be developed so that a cryoprobe can be substituted for the exploring electrode and positioned at the source of activation determined by the map.

An analysis of possible movements of human upper rib cage.

A geometrically realistic mathematical model of the first six ribs and vertebrae of the human rib cage is described. Under the assumption that the individual elements of the rib cage do not deform significantly, the possible range of movements of the model are determined subject to the constraint that the joint surfaces remain in contact. It is shown that normal movements of the ribs cannot be described as a rotation about a single fixed axis. The possible movements of the ribs are analyzed in terms of the misfit incurred at the costovertebral joint surfaces. This analysis shows that there is a movement, corresponding to lateral expansion of the rib for an increase in anteroposterior diameter, in which the misfit at the joint is minimized and also that small deviations from this movement involve only very small degrees of misfit at the joint surfaces. It is concluded that many observed "deformations" of the chest wall can be explained by rigid ribs and normal movements at the costovertebral joints. The interaction between the ribs and the spine is analyzed. It is shown that there can be considerable independent movement of the sternum and the spine, thus allowing mobility of the spine without forcing concomitant movements of rib cage.

An analysis of action of intercostal muscles in human upper rib cage.

The actions of the intercostal and paraspinal muscles in stabilizing the human upper rib cage have been analyzed using a geometrically realistic mathematical model of the first six ribs, vertebrae, and associated musculature. The model suggests roles of the deep layers of erector spinae in stabilizing the vertebral column so that it can support the loads placed upon it by the ribs under physiological load. If we assume that the tension exerted by an intercostal muscle is proportional to its local thickness, the model predicts that the observed distribution of intercostal thickness is close to that which minimizes the stresses in ribs when the model is subjected to peak physiological load. The observed shape of the ribs are optimal to withstand the calculated pattern of loading along their length. These calculations raise the hypothesis that the arrangement of intercostal musculature and rib geometry result in an optimally light rib cage, which is capable of withstanding the loads placed upon it. The analysis of the mechanics of the entire model indicates that the geometrical simplifications made in Hamberger's model are not valid when applied to the rib cage.

Automated optical measurements of human torso surface movements during breathing.

An automated light-sectioning system has been developed for continuously measuring the movements of the torso surface during breathing. The body is illuminated with planes of light of a known geometry, and the body is visualized with television cameras. The perceived angles at which the television scan detected the planes projected onto the body are encoded digitally and stored continuously on magnetic tape. Subsequently the geometry of the torso can be reconstructed at 80-ms intervals enabling the detailed pattern of movements and volume displacement over the torso surface to be determined. Displacements of 0.5 mm over the torso surface can be resolved, and respired volume can be measured to within 10% over the range of the vital capacity.

Positive end-expiratory pressure in weaning patients from controlled ventilation. A prospective randomised trial.

Twenty-five patients in acute respiratory failure were randomised to receive either 5 cm of positive end-expiratory pressure (P.E.E.P.) or no-P.E.E.P. while weaning from controlled ventilation. The use of P.E.E.P. resulted in a significant reduction in the increase in alveolar-arterial oxygen tension gradient (AaDO21) which occurred in the group of patients who were converted from controlled ventilation to spontaneous ventilation without P.E.E.P. Patients who weaned without P.E.E.P. had a mean increase in AaDO21 of 102+/-35 mm Hg S.E. while those who weaned with P.E.E.P. had a mean increase of only 10+/-22 mm Hg (P less than 0-03). The use of P.E.E.P. was also associated with a significant improvement in the vital capacity and the maximum inspiratory force. Patients who weaned with P.E.E.P. had an increase in vital capacity of 258+/-108 ml (P less than 0-05) and an increase in inspiratory force of -15+/-5 cm H2O (P less than 0-01), while patients who weaned without P.E.E.P. did not have significant changes in these measurements. The use of P.E.E.P. during weaning may be helpful in patients who fail to wean because of the development of hypoxaemia due to rapid alveolar collapse, since P.E.E.P. appears to minimise the increase in intrapulmonary right-to-left shunt which normally occurs during weaning from controlled ventilation.