The diagnostic utility of genome sequencing in a pediatric cohort with suspected mitochondrial disease.

PURPOSE: The utility of genome sequencing (GS) in the diagnosis of suspected pediatric mitochondrial disease (MD) was investigated. METHODS: An Australian cohort of 40 pediatric patients with clinical features suggestive of MD were classified using the modified Nijmegen mitochondrial disease severity scoring into definite (17), probable (17), and possible (6) MD groups. Trio GS was performed using DNA extracted from patient and parent blood. Data were analyzed for single-nucleotide variants, indels, mitochondrial DNA variants, and structural variants. RESULTS: A definitive MD gene molecular diagnosis was made in 15 cases and a likely MD molecular diagnosis in a further five cases. Causative mitochondrial DNA (mtDNA) variants were identified in four of these cases. Three potential novel MD genes were identified. In seven cases, causative variants were identified in known disease genes with no previous evidence of causing a primary MD. Diagnostic rates were higher in patients classified as having definite MD. CONCLUSION: GS efficiently identifies variants in MD genes of both nuclear and mitochondrial origin. A likely molecular diagnosis was identified in 67% of cases and a definitive molecular diagnosis achieved in 55% of cases. This study highlights the value of GS for a phenotypically and genetically heterogeneous disorder like MD.

Unfractionated heparin use after percutaneous coronary intervention: results of a trial with a vascular ultrasound endpoint.

BACKGROUND: Previous studies in the pre-stent era have evaluated the postprocedural use of unfractionated heparin (UFH) on clinically defined vascular complications and ischaemic cardiac complications. We prospectively evaluated the benefits and risks of this practice, using vascular ultrasound determined endpoints in the current stent era. METHODS: Patients undergoing percutaneous coronary intervention (PCI) and enrolled in two of our previous routine and prospective vascular ultrasound studies were included in the analysis. Generally the decision to use UFH after sheath removal was at the discretion of the operator, however a subset of patients was randomised to receive UFH or not. Femoral vascular ultrasound was performed prior to hospital discharge and interpreted by an experienced vascular ultrasonographer blinded to whether UFH was used or not. The primary endpoint was a composite of significant vascular ultrasound determined complications including major haematoma, pseudoaneurysm, arterio-venous fistula, femoral venous or arterial thrombosis and retroperitoneal haemorrhage. Secondary endpoints included in hospital ischaemic events, length of stay and outcome at 30 days. RESULTS: A total of 530 patients (43% receiving UFH) were included in the analysis. The incidence of the primary endpoint for the entire population was 4.0% in both the UFH and no UFH groups (p=1.00). In the 226 (43%), randomised patient subset, the primary endpoint occurred in 5.2% in the UFH group and 4.5% in the no UFH group (p=0.80). Time to ambulation and discharge was similar in both groups. At 30 days, the incidence of major adverse cardiac events (4.7% for entire cohort) was similar in all groups whether randomised or not. CONCLUSIONS: When vascular ultrasound is used to determine major vascular complications the use of UFH after PCI in the stent era was not associated with increased major vascular complications. We also failed to provide evidence of a meaningful clinical benefit with the routine use of postprocedural heparin in this selected patient cohort.

Comparison of 6 and 7 French guiding catheters for percutaneous coronary intervention: results of a randomised trial with a vascular ultrasound endpoint.

OBJECTIVE: To perform a randomized, ultrasound controlled trial to define the procedural and clinical advantages and limitations of 6 French (Fr) compared with 7 Fr transfemoral coronary intervention in the stenting era. BACKGROUND: The use of 7 Fr guiding catheters may facilitate Percutaneous Coronary Intervention (PCI), but may be associated with increased vascular complications when compared with 6 Fr catheters. METHODS: Patients undergoing PCI considered suitable for either a 6 or 7 Fr sheath and guiding catheter system were included. All vascular sheaths were removed with assisted manual compression. Femoral vascular ultrasounds were performed prior to hospital discharge and interpreted by a vascular surgeon blinded to treatment assignment. The primary endpoint was a composite of significant vascular complications including major haematoma, retroperitoneal haematoma, pseudoaneurysm, arterio-venous fistula, or femoral venous or arterial thrombosis. RESULTS: During the study, 414 patients (mean age 61+/-11 years, 27% females) were randomly assigned to 6 Fr or 7 Fr sheath groups. The incidence of major vascular complications was 5.7% in the 6 Fr group and 3.9% in the 7 Fr group (P=0.383). There was no significant difference in procedural or angiographic success between the groups. The use of contrast volume was higher in the 7 Fr group (157+/-58 ml vs. 144+/-58 ml; P=0.029). There was a trend toward better operator satisfaction with the 7 Fr guide (P=0.08). CONCLUSIONS: This prospective, randomized trial indicates no reduction in major peripheral vascular complications with the use of smaller guiding catheters in PCI. There was less contrast used in the 6 Fr group, which may benefit some patient subsets, however operators tended to prefer the larger 7 Fr system. The target coronary anatomy and need for complex device intervention should mandate the choice of guiding catheter size, not a perceived impact on vascular complications.

Patient tolerance and resource utilization associated with an arterial closure versus an external compression device after percutaneous coronary intervention.

We assessed patient tolerance and resource utilization of using the AngioSeal closure device versus assisted manual compression using the Femostop device after percutaneous coronary intervention (PCI). Patients undergoing PCI with clean arterial access and no procedural hematoma were randomized to receive the AngioSeal or Femostop device to achieve femoral arterial hemostasis. Times from procedure end to removal from angiography table, hemostasis, ambulation, and hospital discharge were recorded. Bedside nursing/medical officer care time, vascular complications, and disposable use were also documented. Patient comfort was assessed using Present Pain Intensity and Visual Analogue scales at baseline, 4 hr, 8 hr, and the morning after the procedure. One hundred twenty-two patients were enrolled (62 AngioSeal, 60 Femostop). Patients in the AngioSeal group took longer to be removed from the angiography table (11 +/- 4 vs. 9 +/- 3 min; P = 0.002) compared with the Femostop group. Time to hemostasis (0.4 +/- 1.1 vs. 6.4 +/- 1.7 hr; P < 0.001) and ambulation (17 +/- 8 vs. 22 +/- 13 hr; P = 0.004) were less in the AngioSeal group, although time to discharge was not different. Nursing and medical officer time was no different. Disposables including device cost were higher in the AngioSeal group (209 dollars +/- 13 vs. 53 dollars +/- 9; P < 0.001). On a Visual Analogue scale, patients reported more pain at 4 hr (P < 0.001) and 8 hr (P < 0.001) in the Femostop group. The worst amount of pain at any time point was also more severe in the Femostop group (P < 0.001). Similar results were found on a Present Pain Intensity scale of pain. There were no differences in ultrasound-determined vascular complications (two each). Femoral access site closure using the AngioSeal device resulted in a small delay in leaving the angiography suite and a higher disposable cost compared to using the Femostop device. However, patients receiving the AngioSeal were able to ambulate sooner and reported less pain, which may justify the increased costs involved.