Mutations in ERGIC1 cause Arthrogryposis multiplex congenita, neuropathic type.

Arthrogryposis multiplex congenita (AMC) is heterogeneous group of disorders characterized by non-progressive joint contractures from birth that involve more than 1 part of the body. There are various etiologies for AMC including genetic and environmental depends on the specific type, however, for most types, the cause is not fully understood. We previously reported large Israeli Arab kindred consisting of 16 patients affected with AMC neuropathic type, and mapped the locus to a 5.5 cM interval on chromosome 5qter. Using whole exome sequencing, we have now identified homozygous pathogenic variant in the ERGIC1 gene within the previously defined linked region. ERGIC1 encodes a cycling membrane protein which has a possible role in transport between endoplasmic reticulum and Golgi. We further show that this mutation was absent in more than 200 samples of healthy unrelated individuals of the Israeli Arab population. Thus, our findings expand the spectrum of hereditary AMC and suggest that abnormalities in protein trafficking may underlie AMC-related disorders.

Microcephaly, intractable seizures and developmental delay caused by biallelic variants in TBCD: further delineation of a new chaperone-mediated tubulinopathy.

Microtubule dynamics play a crucial role in neuronal development and function, and several neurodevelopmental disorders have been linked to mutations in genes encoding tubulins and functionally related proteins. Most recently, variants in the tubulin cofactor D (TBCD) gene, which encodes one of the five co-chaperones required for assembly and disassembly of α/ß-tubulin heterodimer, were reported to underlie a recessive neurodevelopmental/neurodegenerative disorder. We report on five patients from three unrelated families, who presented with microcephaly, intellectual disability, intractable seizures, optic nerve pallor/atrophy, and cortical atrophy with delayed myelination and thinned corpus callosum on brain imaging. Exome sequencing allowed the identification of biallelic variants in TBCD segregating with the disease in the three families. TBCD protein level was significantly reduced in cultured fibroblasts from one patient, supporting defective TBCD function as the event underlying the disorder. Such reduced expression was associated with accelerated microtubule re-polymerization. Morpholino-mediated TBCD knockdown in zebrafish recapitulated several key pathological features of the human disease, and TBCD overexpression in the same model confirmed previous studies documenting an obligate dependency on proper TBCD levels during development. Our findings confirm the link between inactivating TBCD variants and this newly described chaperone-associated tubulinopathy, and provide insights into the phenotype of this disorder.

Septic Shock and Multiple Organ Failure After Office Endometrial Sampling.

BACKGROUND: Office endometrial biopsy with a Pipelle cannula is the main method for sampling the endometrial lining. The Pipelle biopsy is safe, efficient, and cost effective. This office endometrial sampling method is also an accurate and safe procedure for endometrial sampling of patients with endometrial carcinoma. It is associated with minimal pain and does not require anesthesia. CASE: Pipelle is the most common method used for sampling the endometrial lining. No data are available of infectious complications related to endometrial biopsy. The incidence is presumed to be negligible. We present an unusual case of a 52-year-old woman who experienced septic shock and multiple organ failure following Pipelle endometrial sampling. CONCLUSION: Lower abdominal pain is the cardinal presenting symptom in woman with pelvic infection. Our case emphasizes that an atypical symptom such as abdominal pain after endometrial biopsy could be a sign of infectious complications.

SLC1A4 mutations cause a novel disorder of intellectual disability, progressive microcephaly, spasticity and thin corpus callosum.

Two unrelated patients, presenting with significant global developmental delay, severe progressive microcephaly, seizures, spasticity and thin corpus callosum (CC) underwent trio whole-exome sequencing. No candidate variant was found in any known genes related to the phenotype. However, crossing the data of the patients illustrated that they both manifested pathogenic variants in the SLC1A4 gene which codes the ASCT1 transporter of serine and other neutral amino acids. The Ashkenazi patient is homozygous for a deleterious missense c.766G>A, p.(E256K) mutation whereas the Ashkenazi-Iraqi patient is compound heterozygous for this mutation and a nonsense c.945delTT, p.(Leu315Hisfs*42) mutation. Structural prediction demonstrates truncation of significant portion of the protein by the nonsense mutation and speculates functional disruption by the missense mutation. Both mutations are extremely rare in general population databases, however, the missense mutation was found in heterozygous mode in 1:100 Jewish Ashkenazi controls suggesting a higher carrier rate among Ashkenazi Jews. We conclude that SLC1A4 is the disease causing gene of a novel neurologic disorder manifesting with significant intellectual disability, severe postnatal microcephaly, spasticity and thin CC. The role of SLC1A4 in the serine transport from astrocytes to neurons suggests a possible pathomechanism for this disease and implies a potential therapeutic approach.

Direct Transcatheter Valve Deployment via Sternotomy for Complex Aortic Valve Reoperation.

Reoperative aortic valve replacement is associated with increased morbidity. Valve-in-valve transcatheter aortic valve replacement offers a less invasive alternative to traditional reoperation. However, cases of valve failure after valve-in-valve transcatheter aortic valve replacement represent a complex surgical challenge. We present a case requiring a complex reoperative aortic valve replacement due to structural valve deterioration after multiple previous valve-in-valve transcatheter aortic valve replacements. We performed removal of 3 previous valve-in-valve transcatheter aortic valves, bioprosthetic leaflet excision, and intentional bioprosthetic fracture under direct vision for annular enlargement. This facilitated direct insertion of a new transcatheter aortic valve for expedient and successful management of recurrent aortic stenosis in a very high-risk patient. Creative use of leaflet excision, intentional bioprosthetic fracture, and insertion of a new transcatheter aortic valve under direct vision, proved efficient and successful in a high-risk patient with few surgical options.

Mitochondrial Transfer Ameliorates Cognitive Deficits, Neuronal Loss, and Gliosis in Alzheimer's Disease Mice.

Pathogenesis of neurodegenerative diseases involves dysfunction of mitochondria, one of the most important cell organelles in the brain, with its most prominent roles in producing energy and regulating cellular metabolism. Here we investigated the effect of transferring active intact mitochondria as a potential therapy for Alzheimer's disease (AD), in order to correct as many mitochondrial functions as possible, rather than a mono-drug related therapy. For this purpose, AD-mice (amyloid-ß intracerebroventricularly injected) were treated intravenously (IV) with fresh human isolated mitochondria. One to two weeks later, a significantly better cognitive performance was noticed in the mitochondria treated AD-mice relative to vehicle treated AD-mice, approaching the performance of non-AD mice. We also detected a significant decrease in neuronal loss and reduced gliosis in the hippocampus of treated mice relative to untreated AD-mice. An amelioration of the mitochondrial dysfunction in brain was noticed by the increase of citrate-synthase and cytochrome c oxidase activities relative to untreated AD-mice, reaching activity levels of non-AD-mice. Increased mitochondrial activity was also detected in the liver of mitochondria treated mice. No treatment-related toxicity was noted. Thus, IV mitochondrial transfer may possibly offer a novel therapeutic approach for AD.

Outcomes of delayed sternal closure after complex aortic surgery.

OBJECTIVE: Open chest management during complex proximal aortic surgery may sometimes be necessary. Infectious complications such as mediastinitis and late aortic graft infection remain a concern. The objective of this study was to report our experience with open chest management and delayed sternal closure after complex proximal aortic surgery. METHODS: Between 1991 and 2007, 12 patients (1.2%, 12/1011) required open chest management and delayed sternal closure. Eight patients were men (67%), with a mean age of 56 years (range 28-83 years). Four cases involved redo-median sternotomy (33%) and seven cases (58%) involved acute dissection. All procedures were performed using total cardiopulmonary bypass with profound hypothermic circulatory arrest. Reasons for open chest management included hemodynamic instability, mediastinal edema, bleeding, and respiratory compromise. RESULTS: In-hospital mortality was 16.7% (2/12). Delayed sternal closure was achieved in 92% of patients (11/12). Mean time to closure was 3 days (range 1-9 days). Five patients (42%) required one or more mediastinal explorations prior to final closure. Mean length of stay was 51 days (range 1-186 days). Significant predictors of open chest management were pump time (p<0.0001) and intra-operative blood transfusions (p<0.002). Mean follow-up was 60 months (range 8-106 months). No patients developed mediastinitis or aortic graft infection during postoperative follow-up. CONCLUSIONS: Open chest management with delayed sternal closure after complex aortic repairs may be performed with acceptable mortality. Open chest management does not appear to increase the risk of infectious complications (mediastinitis or graft infections) during complex proximal aortic replacement.

Intraoperative skeletal muscle ischemia contributes to risk of renal dysfunction following thoracoabdominal aortic repair.

OBJECTIVE: Renal dysfunction is among the most commonly occurring morbidities following descending thoracic and thoracoabdominal aortic repair. We hypothesized that myoglobin nephrotoxicity might arise from leg ischemia caused by femoral artery cannulation, which is required for distal aortic perfusion. Lacking complete historical laboratory data on myoglobinemia, we studied somatosensory evoked potential (SSEP) changes in the leg (a functional marker of leg ischemia), as a surrogate predictor of acute postoperative renal failure. METHODS: Intraoperative leg SSEP function and preoperative glomerular filtration rate (GFR - an essential covariate) were available for 299 patients. Change in SSEP was defined as 10% increase in latency or 50% decrease in amplitude. Postoperative renal dysfunction was 1mg/dl/day increase in creatinine for 2 days, clinical diagnosis of ARF or need for dialysis postoperatively. RESULTS: Change in SSEP in the cannulated leg occurred in 108/299 (36%) of cases intraoperatively. All recovered normal SSEP function at decannulation. Patients with SSEP changes had 41/108 (38%) postoperative renal failure compared to 49/191 (26%) without (odds ratio 1.8, p<0.03). Modeled with GFR, aneurysm extent, and chronic obstructive pulmonary disease (COPD), SSEP changes had an adjusted odds ratio of 1.9, p<0.03. Pre-op GFR was also a highly significant predictor of postoperative renal failure (OR 0.98/ml; p<0.0001). CONCLUSION: This is the first study to show a relationship between intraoperative leg ischemia and postoperative renal failure. It provides epidemiological evidence that the ischemic leg may be an important contributor to rhabdomyolysis-like renal morbidity after thoracoabdominal aortic surgery.

Mutations in AIFM1 cause an X-linked childhood cerebellar ataxia partially responsive to riboflavin.

BACKGROUND: AIFM1 encodes a mitochondrial flavoprotein with a dual role (NADH oxidoreductase and regulator of apoptosis), which uses riboflavin as a cofactor. Mutations in the X-linked AIFM1 were reported in relation to two main phenotypes: a severe infantile mitochondrial encephalomyopathy and an early-onset axonal sensorimotor neuropathy with hearing loss. In this paper we report two unrelated males harboring AIFM1 mutations (one of which is novel) who display distinct phenotypes including progressive ataxia which partially improved with riboflavin treatment. METHODS: For both patients trio whole exome sequencing was performed. Validation and segregation were performed with Sanger sequencing. Following the diagnosis, patients were treated with up to 200 mg riboflavin/day for 12 months. Ataxia was assessed by the ICARS scale at baseline, and 6 and 12 months following treatment. RESULTS: Patient 1 presented at the age of 5 years with auditory neuropathy, followed by progressive ataxia, vermian atrophy and axonal neuropathy. Patient 2 presented at the age of 4.5 years with severe limb and palatal myoclonus, followed by ataxia, cerebellar atrophy, ophthalmoplegia, sensorineural hearing loss, hyporeflexia and cardiomyopathy. Two deleterious missense mutations were found in the AIFM1 gene: p. Met340Thr mutation located in the FAD dependent oxidoreductase domain and the novel p. Thr141Ile mutation located in a highly conserved DNA binding motif. Ataxia score, decreased by 39% in patient 1 and 20% in patient 2 following 12 months of treatment. CONCLUSION: AIFM1 mutations cause childhood cerebellar ataxia, which may be partially treatable in some patients with high dose riboflavin.

Outcomes of medical management of acute type B aortic dissection.

BACKGROUND: Currently, the optimal treatment of acute type B aortic dissection remains controversial. The purpose of this study was to report early clinical outcomes of medical management for acute type B aortic dissection. METHODS AND RESULTS: Between January 2001 and March 2005, 129 consecutive patients with the confirmed diagnosis of acute type B aortic dissection were studied. Mean age was 61 years (range, 29 to 94), with 33.3% (43/129) female. Acute type B aortic dissection protocol was instituted with the intent to manage all patients medically. Indications for surgical intervention included rupture, aortic expansion, malperfusion, and intractable pain. All patients were followed-up after discharge. Hospital mortality was 10.1% (13/129), 19% (4/21) when vascular intervention was required, and 8.3% (9/108) when medical management was maintained. Early intervention was required in 21 cases (16.2%), 19 (14.7%) open vascular/aortic cases and 2 cases (1.6%) of percutaneous aortic interventions. Morbidity included rupture (4.7%), stroke (4.7%), paraplegia (8.5%), bowel ischemia (7%), acute renal failure (21%), dialysis requirement (13%), and peripheral ischemia (4.7%). Late vascular-related procedures were performed in 5.2% (6/116) of cases. Univariate risk factors for early mortality were rupture (P<0.0001), need for laparotomy (P<0.008), acute renal failure (P<0.0001), need for dialysis (P<0.0001), and lower extremity ischemia (P<0.0004). The only independent risk factors for hospital mortality by multiple logistic regression was rupture (P<0.0009), and independent risk factors for midterm death were history of chronic obstructive pulmonary disease (P<0.002) and low glomerular filtration rate (<57 mL/min; P<0.0001). CONCLUSIONS: Medical management for acute type B aortic dissection is associated acceptable outcomes. Outcomes of other management strategies, eg, endovascular stenting, for acute type B aortic dissection need to be compared with these results.

Multilevel somatosensory evoked potentials and cerebrospinal proteins: indicators of spinal cord injury in thoracoabdominal aortic aneurysm surgery.

OBJECTIVE: Multilevel somatosensory evoked potentials (SSEP) and the release of biochemical markers in cerebrospinal fluid (CSF) were investigated to identify patients with spinal cord ischemia during thoracoabdominal aortic repair and/or a vulnerable spinal cord during the postoperative period. METHODS: Thirty-nine consecutive patients undergoing elective aneurysm repair using distal aortic perfusion and cerebrospinal fluid drainage were studied. Continuous SSEP were monitored using nerve stimulation of the right and left posterior tibial nerves with signal recording at the level of both common peroneal nerves, the cervical cord and at the cortical level. CSF concentrations of the markers glial fibrillary acidic protein (GFAp), the light subunit of neurofilament triplet protein (NFL), and S100B were determined at different time points from before surgery until 3 days postoperatively. RESULTS: SSEP indicated spinal cord ischemia in two patients leading to additional intercostal artery reattachments. In one of them the signal loss was permanent and the patient woke up with paraplegia. In the other the signal returned but the patient later developed delayed paraplegia. Three patients without SSEP indications of spinal cord ischemia during surgery later developed delayed paraplegia. The patients with spinal cord symptoms had significant increases, during the postoperative period of CSF biomarkers GFAp (571-fold), NFL (14-fold) and S100B (18-fold) compared to asymptomatic patients. GFAp increased before or in parallel to onset of symptoms in the patients with delayed paraplegia. CONCLUSIONS: Peroperative multilevel SSEP has a high specificity in detecting spinal cord ischemia but does not identify all patients with a postoperative vulnerable spinal cord. Biochemical markers in CSF increase too late for intraoperative monitoring but GFAp is promising for identifying patients at risk for postoperative delayed paraplegia.

Cerebral monitoring with transcranial Doppler ultrasonography improves neurologic outcome during repairs of acute type A aortic dissection.

OBJECTIVE: Neurologic complications after repair of acute type A aortic dissection remain significant. The use of power M-mode transcranial Doppler monitoring to verify cerebral blood flow during these repairs might decrease cerebral ischemia by correcting malperfusion. The purpose of this study was to analyze the use of power M-mode transcranial Doppler monitoring during repairs of acute type A dissection with regard to neurologic outcome. METHODS: We performed a prospective study of patients undergoing repairs of acute type A aortic dissection. Repairs included profound hypothermic circulatory arrest and retrograde cerebral perfusion. Patients in whom transcranial Doppler monitoring was used to monitor cerebral blood flow and modify operative technique during repair (study group) were compared with those without monitoring and modification (control group). RESULTS: Between September 2001 and October 2003, we repaired 56 cases of acute type A dissection. Power M-mode transcranial Doppler monitoring was used in 50% (28/56) of cases. Power M-mode transcranial Doppler monitoring altered operative cannulation and guided retrograde cerebral perfusion flow in 28.5% (8/28) and 78.6% (22/28) of cases, respectively. Two patients presented with preoperative stroke, one in each group. One operative death occurred in each group. In-hospital mortality and the occurrence of new stroke were not significantly different between the 2 groups. Temporary neurologic dysfunction occurred less often in the study group (14.8% [4/27] vs 51.8% [14/27], P = .008). CONCLUSIONS: Identification of cerebral malperfusion requires cerebral monitoring. By ensuring cerebral blood flow by using power M-mode transcranial Doppler monitoring and correcting cerebral malperfusion by modifying operative technique, neurologic outcome was improved during repairs of acute type A aortic dissection.

Superior vena caval bypass using the superficial femoral vein for treatment of superior vena cava syndrome.

We present the case of a 71-year-old woman who had benign, symptomatic, superior vena cava syndrome that was treated with open surgical bypass using the superficial femoral vein. The patient had an uneventful hospital course and experienced relief of her symptoms. We conclude that the superficial femoral vein is an acceptable bypass conduit for open surgical management of superior vena cava syndrome.

Surgical repair of extensive aortic aneurysms.

We present our 14-year experience in the management of extensive aortic aneurysms. Significant progress has been made in reducing the morbidity and mortality associated with these procedures. Our strategies for organ protection, operative techniques, including the elephant trunk technique, and surgical results are discussed.

Preoperative and operative predictors of delayed neurologic deficit following repair of thoracoabdominal aortic aneurysm.

PURPOSE: Delayed neurologic deficit has been recognized in recent years as a source of morbidity following thoracic and thoracoabdominal aortic repair. We wanted to find risk factors specifically significant for delayed neurologic deficit. In this initial study we looked at preoperative and operative risk factors. METHODS: We performed 854 thoracoabdominal aortic repairs between February 1991 and May 2001. For this study we excluded 26 patients who died before postoperative neurologic status could be evaluated and 38 who had immediate neurologic deficit on initial postoperative evaluation, leaving 790 consecutive patients. We evaluated a wide range of demographic, preoperative physiological and intraoperative data, using univariate and multivariable statistical analyses. RESULTS: Twenty-one of 790 (2.7%) patients had delayed neurologic deficit. Significant univariate predictors included preoperative renal dysfunction (odds ratio 5.9; P <.006), acute dissection (odds ratio 3.9; P <.05), extent II thoracoabdominal aorta (odds ratio 3.0; P <.03), and use of adjuncts (cerebrospinal fluid drainage and distal aortic perfusion; odds ratio 7.7; P <.03). The use of the adjuncts dropped from the multivariable model but all other factors remained. No other significant risk factors were identified. Twelve of 21 (57%) patients recovered neurologic function with optimization of blood pressure and cerebrospinal fluid drainage. CONCLUSION: Preoperative renal dysfunction, acute dissection, and extent II thoracoabdominal aorta are significant predictors of delayed neurologic deficit. Previous studies have demonstrated that the use of adjuncts protects against immediate neurologic deficit. The findings of this study are consistent with the hypothesis that adjuncts reduce ischemic insult enough to prevent immediate neurologic deficit but that a period of increased spinal cord vulnerability persists several days postoperatively.

Replacement of the ascending and transverse aortic arch: determinants of long-term survival.

BACKGROUND: Although little has been published on the natural history of aneurysms of the ascending aorta and aortic arch, long-term prognosis of untreated aneurysms is generally poor. We reviewed our 10-year experience in the repair of the ascending aorta and aortic arch to evaluate long-term outcome. METHODS: Between January 1991 and May 2001, we repaired 423 aneurysms of the ascending aorta or aortic arch using profound hypothermic circulatory arrest. Median age was 65 years. Retrograde cerebral perfusion (RCP) was used in 357 cases. Mean pump and RCP times were 139 and 33.9 minutes, respectively. Survival was ascertained by direct patient contact or by searching the social security death index. Survival was analyzed by Kaplan-Meier stratified analysis and by multivariate Cox regression. RESULTS: Overall actuarial survival was 72% at 5 years and 71% at 10 years after surgery. Univariate analysis identified increasing age (p < 0.0001), chronic obstructive pulmonary disease (p < 0.014), concurrent unoperated aneurysm (p < 0.005), arch involvement (p < 0.042), pump time (p < 0.0004), concurrent aortic valve replacement (p < 0.009), and postoperative renal failure (p < 0.0002) as factors that negatively influenced survival. Multivariate analysis identified increasing age (p < 0.0001) and pump time (p < 0.0001). RCP did not have a significant independent effect on the long-term survival. CONCLUSIONS: Our experience indicates that repair of the ascending aorta and aortic arch can be accomplished with good long-term survival.

Staged repair of extensive aortic aneurysms.

BACKGROUND: We adopted a two-stage approach (elephant trunk procedure) in the repair of extensive aortic aneurysms in 1991, performing 241 procedures in 155 patients. METHODS: Reversed elephant trunk (graft replacement of the descending thoracic aorta followed by ascending/arch replacement) was performed in 18 patients. All other patients underwent conventional staged repair. The first stage was performed in 137 patients, with 86 patients returning for the second stage. RESULTS: First stage 30-day mortality was 9.5% (13 of 137). There was no second stage immediate neurologic deficit. Second stage mortality was 7.0% (6 of 86). During the interval of 31 days to 6 weeks after stage one, mortality was 10 of 124 (8%). Seven of the 10 interval deaths (70%) were due to rupture of the untreated aortic segment. The mortality rate was 32.1% (18 of 56) in the group of patients who did not return for the second stage repair. CONCLUSIONS: Extensive aortic aneurysms can be repaired with acceptable morbidity and mortality using the elephant trunk technique. After stage one, prompt treatment of the remaining aneurysm is crucial to success.

Determination of cerebral blood flow dynamics during retrograde cerebral perfusion using power M-mode transcranial Doppler.

BACKGROUND: Retrograde cerebral perfusion (RCP) during profound hypothermic circulatory arrest has been used as an adjunct for cerebral protection for repairs of the ascending and transverse aortic arch. Transcranial Doppler ultrasound has been used to monitor cerebral blood flow during RCP with varying success. The purpose of this study was to characterize cerebral blood flow dynamics during RCP using a new mode of monitoring known as transcranial power motion-mode (M-mode) Doppler ultrasound. METHODS: Data on pump-flow characteristics and patient outcomes were collected prospectively for patients undergoing ascending and transverse aortic arch repair. Retrograde cerebral perfusion during profound hypothermic circulatory arrest was used for all operations. Intraoperative cerebral blood flow dynamics were monitored and recorded using transcranial power M-mode Doppler ultrasound. RESULTS: Between August 2001 and March 2002, we used transcranial power M-mode Doppler ultrasound monitoring for 40 ascending and transverse aortic arch repairs during RCP. Mean RCP time was 32.2 +/- 13.8 minutes. Mean RCP pump flow and RCP peak pressure for identification of cerebral blood flow were 0.66 +/- 0.11 L/min and 31.8 +/- 9.7 mm Hg, respectively. Retrograde cerebral blood flow during RCP was detected in 97.5% of cases (39 of 40 patients) with a mean transcranial power M-mode Doppler ultrasound flow velocity of 15.5 +/- 12.3 cm/s. In the study group, 30-day mortality was 10.0% (4 of 40 patients). The incidence of stroke was 7.6% (3 of 40 patients); the incidence of temporary neurologic deficit was 35.0% (14 of 40 patients). CONCLUSIONS: Transcranial power M-mode Doppler ultrasound consistently demonstrated retrograde middle cerebral artery blood flow during RCP. Transcranial power M-mode Doppler ultrasound can provide optimal RCP with individualized settings of pump flow.

A correlation between the structure of myocardial cells and prolonged Q-T interval in young rats.

In the present study, we examined the electrocardiogram and the structure of myocardial cells in young rats at different postnatal ages. The offspring of rats were sacrificed on different postnatal days following electrocardiographical recordings, and sections of their hearts were examined microscopically. In a number of newborns, we observed definite prolongation of the Q-T interval in the electrocardiogram on the first day of life. Normal shortening of the Q-T interval with age was demonstrated in the majority of the offspring while, in some of them, the Q-T interval remained prolonged. In the "affected" offspring, which exhibit a typical pattern of Q-T prolongation with clear ST segment, definite retardation of histological differentiation of the myocardium was found at various ages. In these cases, there were large numbers of "myoblasts" scattered between normal myocytes in different parts of the ventricular walls and septum. These myoblasts were rarely identified in newborns and offspring with a normal Q-T interval. Our results clearly show a correlation between the ratio of persistence of undifferentiated myoblasts at any age and the typical prolonged Q-T pattern in the electrocardiogram (r = 0.9). Due to the possible clinical significance, the hearts of patients with prolonged Q-T syndrome should be examined so as to reach for abnormal differentiation of the myocytes.

Cardiac function predicts mortality following thoracoabdominal and descending thoracic aortic aneurysm repair.

OBJECTIVE: Previous studies have identified age, renal failure and aneurysm extent as predictors of mortality following thoracoabdominal and descending thoracic aortic aneurysm (TAA) repair. We studied the impact of coronary artery disease (CAD) and cardiac function on 30-day mortality following TAA repair. METHODS: Between February 1991 and May 2001, we performed 854 TAA repairs. Two hundred ninety-one patients (34%) had a history of coronary artery disease. One hundred forty-one/291 (49%) had undergone coronary artery bypass surgery (CAB) prior to TAA repair. We conducted multivariable analyses of known risk factors along with the left ventricular ejection fraction (EF) and prior CAB to determine the adjusted effect of CAD on outcome. RESULTS: Mortality in patients with CAD was 54/291 (18%) compared to 75/563 (13%) without CAD (P<0.05). In patients who had prior CAB, mortality was 31/141 (22%) compared to 98/713 (14%) patients without prior CAB, (P<0.02). In multivariable analysis, the effects of CAD and CAB on mortality were eliminated by consideration of a low EF (defined as less than 50%). CONCLUSION: Impaired left ventricular function appears to be the strongest cardiac predictor of mortality for TAA repair, independent of the presence of coronary artery disease or coronary artery bypass revascularization.