Biventricular pacing diminishes the need for implantable cardioverter defibrillator therapy. Ventak CHF Investigators.

OBJECTIVES: We sought to test the postulate that biventricular pacing diminishes the need for appropriate tachycardia therapy. We reviewed the frequency of therapy in patients, serving as their own controls, who were enrolled in the Ventak CHF (congestive heart failure) biventricular pacing study. BACKGROUND: It is well established that both acute and chronic CHF contribute to the need for tachyarrhythmia therapy in recipients of an automatic implantable cardioverter defibrillator (ICD). Synchronized biventricular (BV) pacing is a new and promising therapy for symptomatic improvement of CHF in selected patients (low ejection fraction, intraventricular conduction delay). We postulate that this pacing therapy will diminish the need for tachyarrhythmia therapy. METHODS: Participants in the Ventak CHF trial received a triple-chamber biventricular ICD with a transvenous right ventricular lead and a left ventricular (LV) lead placed via thoracotomy. Of 54 patients enrolled in the Ventak CHF trial, 32 could be analyzed, with each completing three blinded months programmed to BV VDD pacing and a second randomly assigned three-month period of no pacing. RESULTS: Of the 32 patients, 13 (41%) received appropriate therapy for a ventricular tachyarrhythmia at least once in the six-month monitoring period postimplant. Five patients (16%) had at least one tachyarrhythmic episode while programmed to BV pacing, whereas 11 (34%) had at least one episode while programmed to no pacing. Three patients (9%) received therapy in both pacing periods, two with BV pacing only. The decrease in necessary tachycardia therapy during the BV pacing period was statistically significant (p = 0.035). CONCLUSIONS: In patients with standard ICD indications who also have CHF, LV dysfunction, and an intraventricular conduction delay, ICD therapy is less common with BV pacing. The mechanism for this improvement is unclear but may be related to hemodynamic improvement in CHF. Although BV pacing does not obviate the need for an ICD, it does diminish the need for appropriate tachyarrhythmia therapy in selected patients.

The first year experience with the dual chamber ICD.

In July 1997, a dual chamber pacemaker combined with a tiered therapy implantable cardioverter defibrillator (ICD) first became available in the United States. We report the first-year experience of one center in the United States with this dual chamber ICD. Of a total of 174 ICDs, 95 (55%) were dual chamber devices and 79 (45%) were single chamber. New dual chamber ICD insertions averaged 57.4 +/- 8.9 minutes, though there was a learning curve as the last 30 implants averaged 45.1 +/- 6.1 minutes with a negative slope to the regression line of procedure duration (-0.52, P < 0.05). New single chamber ICD implants were 18.5 minutes quicker (38.9 +/- 7.2 minutes). The most challenging implants were dual chamber upgrades (mean procedure duration 64.9 +/- 15.8 minutes), especially if there was a previously implanted pacemaker and ICD at separate sites. Indications for a new dual chamber device were grouped into classic pacemaker indications (52.5%), which comprised the Class I ACC/AHA guidelines, ICD-specific indications (24.6%), and other (23.0%). In the 34 patients undergoing dual chamber upgrade, the classic and ICD-specific groups were equal (47.0% each). Complications were rare (2.8%), though 3 (8.8%) of 34 undergoing a dual chamber upgrade developed late infections requiring explantation. In its first year, the dual chamber ICD has become a common device at our institution comprising 55% of new implants. As experience grows, we anticipate similar usage at most institutions.

Indications for implantation of a dual-chamber pacemaker combined with an implantable cardioverter-defibrillator.

Of 122 patients with single-chamber implantable cardioverter-defibrillators (ICDs) reviewed retrospectively, 35 had traditional indications, 14 had other indications, and 18 had ICD-specific indications for dual-chamber pacing therapy. Thus, 67 patients (55%) were potential candidates for dual-chamber pacing, which has only recently become available combined with ICD therapy.

ICD restudy: results and potential benefit from routine predischarge and 2-month evaluation.

Evaluation of ICD function can now be performed noninvasively with intravenous sedation. To determine the value of follow-up electrophysiological studies for ICD implants, we performed a retrospective review of predischarge and 2-month ICD re studies, identifying critical problems uncovered. Of the 123 patients implanted, 122 had a predischarge study, 105 had both predischarge and elective 2-month follow-up studies, and 1 patient expired prior to restudy. Patients who underwent 2-month studies for nonelective indications (e.g., frequent shocks) were excluded from analysis. Programming changes were made in 62% of the predischarge studies (n = 122) and 70% of the elective 2-month studies (n = 105). The average number of programming changes per study was 1.3 for predischarge testing and 1.1 for 2-month testing. The most common changes at predischarge testing were adjustment of the tachyarrhythmia rate cutoff (35%) and at 2-month study, reprogramming of bradycardia pacing parameters (41%). Of the patients who underwent both predischarge and 2-month testing, 91% had programming changes in at least one of their re studies. Of 227 re studies performed, 18 studies in 14 patients yielded 24 critical findings which included: DFT increases to > or = 25 J (n = 13); sensing abnormalities of induced ventricular arrhythmia (n = 6); dislodged lead (n = 2); and serious pacemaker interactions (n = 3). Six of these critical cases (5% of total patients) required reoperation. The data suggests that routine ICD restudy is a valuable tool for management of the ICD patient. Additionally, ICD restudy is likely to increase the diagnostic yield of clinically silent critical system problems that could result in device failure.

Recurrent Twiddler's syndrome in a nonthoracotomy ICD system despite a Dacron pouch.

Twiddler's syndrome is a highly recognized yet rare complication of pacemaker and cardioverter defibrillator (i.c.d.) implantation. We present a case in which persistent generator rotation resulted in lead dislodgment and inappropriate shocks in an initial ICD and recurrent lead fracture in a second ICD system. This case is unusual in that even with extensive surgical precautions including use of a Dacron pouch, generator rotation could not be prevented. Submuscular implantation and use of a smaller generator may prevent Twiddler's syndrome.

In vivo regulation of rat muscle glycogen resynthesis after intense exercise.

Time courses of the glycogen synthesis rate and of the glucose 6-phosphate (G-6-P) concentration after an electrically induced exercise were followed in the anesthetized rat gastrocnemius by in vivo 13C and 31P nuclear magnetic resonance (NMR) spectroscopy, respectively. The ratio of glycogen synthase I to glycogen synthase I and D (I/I+D) and allosteric activation by G-6-P were also studied in vitro on muscles sampled at rest and 10 min (early recovery) and 100 min (late recovery) after exercise. From early recovery to late recovery, the in vivo glycogen synthesis rate dropped from 0.46 +/- 0.06 to 0.11 +/- 0.04 mmol.kg wet tissue-1.min-1, the G-6-P concentration from 0.83 +/- 0.08 to 0.32 +/- 0.05 mmol/kg wet tissue, and I/I+D from 83 +/- 4 to 47 +/- 1%. The combination of the changes in G-6-P concentration and in I/I+D quantitatively describes the fourfold decrease in glycogen synthesis rate from early to late recovery. These results demonstrate that phosphorylation, determining glycogen synthase I/I+D, and allosteric control of glycogen synthase by G-6-P contribute approximately equally to the regulation of the postexercise in vivo glycogen synthesis rate.

The human vertebral column at the end of the embryonic period proper. 3. The thoracicolumbar region.

The present study of the thoracicolumbar region continues an investigation of the vertebral column at 8 postovulartory weeks (the end of the embryonic period proper) by means of graphic reconstructions. The cartilaginous vertebrae have short neural processes associated with the normal spina bifida occulta present at this time. The separate cartilaginous centres that several authors believe to exist in the cervical and lumbar costal elements, but which have not been observed by the present authors, have been thought to be the forerunners of extrathoracic ribs. A distinction needs to be made, however, between such centres and ribs. Similarly, in the fetal period, ossific loci in the costal elements of CV 7 are very frequent, whereas cervical ribs in the adult are relatively rare. The neurocentral joints, and hence the boundaries between neural arches and centra, are unclear before ossification has begun and has progressed during the fetal period. The sternal bands are almost completely united and the scapula is high in position. Neural relationships aid in the determination of homologous parts within the vertebral column, but clarification of corresponding parts has not previously been possible within the embryonic period. Areas ventral to the dorsal rami are ribs in the thoracic region and costal elements in other regions. Areas underlying the dorsal rami are transverse processes in the thoracic region and minute 'true' transverse elements in the cervical and lumbar regions. Thus, the descriptive lumbar transverse processes correspond to the true transverse processes and the ribs in the thoracic region. The dorsal rami of the thoracic nerves pass between the transverse processes and the tubercles of the ribs and then divide. The ventral rami of lumbar Nerves 1 and 2 resemble the thoracic in their course, whereas those of Nerves 3-5 are similar to the sacral. The thoracic dorsal roots are sloping and, associated with the greater height of the lumbar centra, the lumbar roots even more so. The directions of the various dorsal roots reflect differences in growth gradients between vertebral column and spinal cord. The thoracic and lumbar portions of the column change little in proportion during the embryonic period proper.

The human vertebral column at the end of the embryonic period proper. 4. The sacrococcygeal region.

The sacral and coccygeal vertebrae at 8 postovulatory weeks (the end of the embryonic period proper) have been studied by means of graphic reconstructions. The cartilaginous sacrum is now a definitive unit composed of five separable vertebrae, each of which consists of a future centrum and bilateral neural processes. The base of each neural process consists of an anterolateral or alar element, not present in the lumbar region, and a posterolateral part, which includes costal and transverse elements. The usual illustrations, in which the costal component is placed in the alar element, are incorrect. The future dorsal foramina (containing dorsal rami) face laterally in the embryo and are in line with the thoracicolumbar intervertebral foramina. Considerable differential growth is required to change the dorsal openings from a lateral to a dorsal positions. The intervertebral foramina transmit ventral rami, but pelvic foramina are not yet present. The lumbosacral plexus is completed by S.N.1-3; S.N.4, 5 and Co.N.1 form the pelvic plexus. The inferior hypogastric plexus and the hypogastric nerves are present. The sacrum takes part in the spina bifida occulta that characterises the entire length of the embryonic vertebral column. The coccygeal vertebrae, which are variable, were 4-6 in number in the present series. The first is the best developed. The ventriculus terminalis ends usually at the level of Co.V.1 and the spinal cord generally at Co.V.5. The coccygeal notochord ends commonly in bifurcation or trifurcation. 'Haemal arches' were not observed.

The human vertebral column at the end of the embryonic period proper. 2. The occipitocervical region.

The present investigation of the cervical region of the vertebral column at eight post-ovulatory weeks is the first such study based on precise reconstructions of staged embryos. At the end of the embryonic period proper, a typical vertebra is a U-shaped piece of cartilage characterized by spina bifida occulta. The notochord ascends through the centra and leaves the dens to enter the basal plate of the skull. The median column of the axis comprises three parts (designated X, Y, Z) which persist well into the fetal period. They are related to the first, second and third cervical nerves, respectively. Part X may project into the foramen magnum and form an occipito-axial joint. Part Z appears to be the centrum of the axis. The articular columns of the cervical vertebrae are twofold, as in the adult: an anterior (atlanto-occipital and atlanto-axial) and a posterior (from the lower aspect of the axis downwards). Alar and transverse ligaments are present. Cavitation is not found in the embryonic period in either the atlanto-occipital or zygapophysial joints, and is generally not present in the median atlanto-axial joint either. Most of the transverse processes exhibit anterior and posterior tubercles. An 'intertubercular lamella' may or may not be present, i.e. the foramina transversaria are being formed around the vertebral artery. The spinal ganglia are generally partly in the vertebral canal and partly on the neural arches, medial to the articular processes. During the fetal period, the articular processes shift to a coronal position and this alteration appears to be associated with a corresponding change in the location of the spinal ganglia.

The human vertebral column at the end of the embryonic period proper. 1. The column as a whole.

The present investigation of the vertebral column at 8 post-ovulatory weeks, the first such study based on precise reconstructions, has revealed 33 or 34 cartilaginous vertebrae arranged in flexion and approximately 20--33 mm in total length. At the end of the embryonic period proper, a typical vertebra, such as TV6, consists of a centrum that is continuous with two neural processes. Pedicles, articular and transverse processes, but no spinous processes, are identifiable. The tips of the neural processes, which are formed by the laminae, are connected by fibrous tissue and resemble the condition of total rachischisis. The union of the laminae, the onset of ossification, and the appearance of articular cavities are characteristic of the early fetal period. The variations encountered within a single developmental stage were noted. They were mostly minor, e.g. the number of coccygeal elements and the extent of the dorsal growth of the neural processes.

Shape and volume changes in erythrocyte ghosts and spectrin-actin networks.

In response to changes in electrolyte concentration and pH, erythrocyte ghosts can exhibit some of the characteristic shapes seen in the intact erythrocyte. These shape changes are accompanied by volume changes; both are reversible, not energy dependent, and not inhibited by sulfhydryl reagents. The volume reduction can also be seen in isolated Triton-free spectrin-actin lattices, showing that this network is capable of reversible contraction. The results suggest that reversible changes in size of the underlying cytoskeleton of the erythrocyte membrane can control cell shape.

The timing and sequence of events in the development of the human vertebral column during the embryonic period proper.

A documented scheme of the early development of the human vertebrae is presented. It is based on (1) reports of workers who personally studied staged human embryos, and (2) personal observations and confirmations. The necessity of studying staged embryos in order to determine the precise sequence of developmental events is stressed.

The onset of ossification in the human calcaneus.

A (silver) radiographic and microscopic study of the onset of ossification in the calcaneus of 177 human fetuses between 49 and 150 mm C.-R. length has revealed the presence of two independent and developmentally different ossific sites. A lateral locus, intramembranous (parachondral) in origin and precocious in appearance, was observed in slightly over 16% of the fetuses examined between 93 mm (the first appearance of this bone) and 150 mm C.-R. It occupied the vascular connective tissue within the anterior portion of a distinct groove on the inferolateral wall of the cartilaginous calcaneus between the retrotrochlear eminence anterosuperiorly, and the lateral process of the tuber posteroinferiorly. A centrally situated, primary ossific centre, endochondral in origin, was detected in only 11% of the fetuses between 118 mm (the initial appearance of this centre) and 150 mm C.-R. It was situated in the centre of the anterior third of the cartilaginous calcaneus in relation to the sustenaculum tali medially and to a distinct cartilaginous prominence on its lateral surface. Only four fetuses possessed both ossific sites (lateral and central): at 122, 143, 145, and 150 mm C.-R., and in only one of these was continuity established between them. One fetus (122 mm) possessed two independent endochondral centres (superior and inferior).