Outcomes After Endovascular Aortic Intervention in Patients With Connective Tissue Disease.

Importance: Endovascular treatment is not recommended for aortic pathologies in patients with connective tissue diseases (CTDs) other than in redo operations and as bridging procedures in emergencies. However, recent developments in endovascular technology may challenge this dogma. Objective: To assess the midterm outcomes of endovascular aortic repair in patients with CTD. Design, Setting, and Participants: For this descriptive retrospective study, data on demographics, interventions, and short-term and midterm outcomes were collected from 18 aortic centers in Europe, Asia, North America, and New Zealand. Patients with CTD who had undergone endovascular aortic repair from 2005 to 2020 were included. Data were analyzed from December 2021 to November 2022. Exposure: All principal endovascular aortic repairs, including redo surgery and complex repairs of the aortic arch and visceral aorta. Main Outcomes and Measures: Short-term and midterm survival, rates of secondary procedures, and conversion to open repair. Results: In total, 171 patients were included: 142 with Marfan syndrome, 17 with Loeys-Dietz syndrome, and 12 with vascular Ehlers-Danlos syndrome (vEDS). Median (IQR) age was 49.9 years (37.9-59.0), and 107 patients (62.6%) were male. One hundred fifty-two (88.9%) were treated for aortic dissections and 19 (11.1%) for degenerative aneurysms. One hundred thirty-six patients (79.5%) had undergone open aortic surgery before the index endovascular repair. In 74 patients (43.3%), arch and/or visceral branches were included in the repair. Primary technical success was achieved in 168 patients (98.2%), and 30-day mortality was 2.9% (5 patients). Survival at 1 and 5 years was 96.2% and 80.6% for Marfan syndrome, 93.8% and 85.2% for Loeys-Dietz syndrome, and 75.0% and 43.8% for vEDS, respectively. After a median (IQR) follow-up of 4.7 years (1.9-9.2), 91 patients (53.2%) had undergone secondary procedures, of which 14 (8.2%) were open conversions. Conclusions and Relevance: This study found that endovascular aortic interventions, including redo procedures and complex repairs of the aortic arch and visceral aorta, in patients with CTD had a high rate of early technical success, low perioperative mortality, and a midterm survival rate comparable with reports of open aortic surgery in patients with CTD. The rate of secondary procedures was high, but few patients required conversion to open repair. Improvements in devices and techniques, as well as ongoing follow-up, may result in endovascular treatment for patients with CTD being included in guideline recommendations.

Lung Transplantation: A Viable Option for Connective Tissue Disease?

Interstitial lung disease (ILD) and pulmonary hypertension (PH) caused by connective tissue disease (CTD) are one of the main causes of morbidity and death in patients. Although the International Society for Heart & Lung Transplant suggested that ILD and PH related to CTD are rare indications for lung transplantation in 2006, many lung transplantation centers are concerned that the multisystem involvement of CTD will affect survival outcomes after lung transplantation, and CTD is regarded as a relative contraindication for lung transplantation. However, long-term and short-term survival after lung transplantation in CTD patients is similar compared with survival in common indications for lung transplantation such as idiopathic pulmonary fibrosis (IPF), and no higher incidence of complications after transplantation in many lung transplant centers. This suggests that lung transplantation may be beneficial in CTD patients with disease that progresses to end-stage lung disease, and CTD should not be considered a contraindication for lung transplantation. In the future, more prospective studies are needed to analyze the risk factors of lung transplantation in CTD patients to improve survival rates and reduce the risk of complications. This narrative review summarizes the selection and evaluation of candidates for CTD before lung transplantation and describes the clinical outcomes in CTD after lung transplantation in large-capacity lung transplantation center. The purpose of this review is to help rheumatologists decide when to refer patients with CTD-related lung involvement to a lung transplantation center and the conditions to consider before transplantation and to provide confidence to lung transplant experts.

Aortic valve reimplantation in patients with connective tissue disorders: Are the leaflets durable?

OBJECTIVE: The durability of reimplanted myxomatous aortic valves in root replacements for patients with connective tissue disorders (CTD) is unclear; therefore, we sought to evaluate the long-term resilience of these repairs. METHODS: From January 1980 to January 2020, 214 patients with CTD and 645 without CTD underwent primary, elective aortic valve reimplantation operations at Cleveland Clinic. The CTD cohort included 164 (77%) with Marfan, 23 (11%) with Loeys-Dietz, and 7 (3.3%) with Ehlers-Danlos CTD. We accounted for differing patient characteristics between the groups by propensity score matching to compare outcomes, yielding 96 matched pairs. Longitudinal echocardiographic measures were compared using nonlinear mixed effects models. RESULTS: In the CTD cohort, there were no operative mortalities (30-day or in-hospital), 1 (0.47%) stroke, and 1 (0.47%) early in-hospital reoperation for valve dysfunction. Ten-year prevalence of no aortic regurgitation was 86%, mild 11%, and moderate 3%. Ten-year freedom from reoperation was 97%. In propensity matched cohorts, there were no significant differences in in-hospital outcomes, longitudinal aortic regurgitation and mean gradient, risk of reoperation on the aortic valve, or risk of late death. CONCLUSIONS: Aortic valve reimplantation is a durable operation in patients with CTD and root aneurysms. These patients do not experience early degeneration of their reimplanted aortic valves.

Minimally Invasive Beating Heart Mitral Valve Repair in a Patient With Connective Tissue Disease at Prohibitive Risk for Redo Sternotomy.

Sternal reentry when the ascending aorta is adherent to the posterior table of the sternum is associated with substantial risk. A minimally invasive right thoracotomy beating heart approach is an alternative when the aorta cannot be cross-clamped. This report details this technique for a complex reoperative mitral valve repair procedure performed in a patient with connective tissue disease who had required multiple aortic operations and presented with heart failure and severe functional mitral regurgitation.

Managing connective tissue disease: how to select and facilitate successful transplantation.

PURPOSE OF REVIEW: Lung transplant (LTx) evaluation and selection of candidates with connective tissue disease (CTD) remains controversial and varies between centers, and the optimal candidate selection is still controversial. RECENT FINDINGS: Recent United States and European publications have reported reasonable short-term and long-term LTx outcomes in patients with CTD to other lung fibrosis patients without CTD. This article discusses the recently published International Society for Heart and Lung Transplantation (ISHLT) consensus document recommendations to evaluate and select CTD candidates, the importance of early referral, posttransplant management, and the involvement of a multidisciplinary team. SUMMARY: Future standardized practices among centers adapting the 2021 ISHLT consensus recommendations to evaluate and select CTD candidates will allow risk stratification, determine the best candidates, and facilitate the most successful long-term LTx outcomes.

ISHLT consensus document on lung transplantation in patients with connective tissue disease: Part III: Pharmacology, medical and surgical management of post-transplant extrapulmonary conditions statements.

Patients with connective tissues disease (CTD) are often on immunomodulatory agents before lung transplantation (LTx). Till now, there's no consensus on the safety of using these agents perioperative and post-transplant. The International Society for Heart and Lung Transplantation-supported consensus document on LTx in patients with CTD addresses the risk and contraindications of perioperative and post-transplant management of the biologic disease-modifying antirheumatic drugs (bDMARD), kinase inhibitor DMARD, and biologic agents used for LTx candidates with underlying CTD, and the recommendations and management of non-gastrointestinal extrapulmonary manifestations, and esophageal disorders by medical and surgical approaches for CTD transplant recipients.

ISHLT consensus document on lung transplantation in patients with connective tissue disease: Part II: Cardiac, surgical, perioperative, operative, and post-operative challenges and management statements.

Patients with connective tissue disease (CTD) present unique surgical, perioperative, operative, and postoperative challenges related to the often underlying severe pulmonary hypertension and right ventricular dysfunction. The International Society for Heart and Lung Transplantation-supported consensus document on lung transplantation in patients with CTD standardization addresses the surgical challenges and relevant cardiac involvement in the perioperative, operative, and postoperative management in patients with CTD.

ISHLT consensus document on lung transplantation in patients with connective tissue disease: Part I: Epidemiology, assessment of extrapulmonary conditions, candidate evaluation, selection criteria, and pathology statements.

Patients with connective tissue disease (CTD) and advanced lung disease are often considered suboptimal candidates for lung transplantation (LTx) due to their underlying medical complexity and potential surgical risk. There is substantial variability across LTx centers regarding the evaluation and listing of these patients. The International Society for Heart and Lung Transplantation-supported consensus document on lung transplantation in patients with CTD standardization aims to clarify definitions of each disease state included under the term CTD, to describe the extrapulmonary manifestations of each disease requiring consideration before transplantation, and to outline the absolute contraindications to transplantation allowing risk stratification during the evaluation and selection of candidates for LTx.

Status and Recommendations for Incorporating Biomarkers for Cutaneous Neurofibromas Into Clinical Research.

OBJECTIVE: To summarize existing biomarker data for cutaneous neurofibroma (cNF) and to inform the incorporation of biomarkers into clinical trial design for cNFs. METHODS: The cNF working group, a subgroup of the Response Evaluation in Neurofibromatosis and Schwannomatosis (REiNS) consortium, was formed to review and inform clinical trial design for cNFs. Between June 2018 and February 2020, the cNF working group performed a review of existing data on genetic biomarkers for cNFs in the setting of neurofibromatosis type 1. We also reviewed criteria for successful biomarker application in the clinic. The group then held a series of meetings to develop a consensus report. RESULTS: Our systematic literature review of existing data revealed a lack of validated biomarkers for cNFs. In our report, we summarize the existing signaling, genomic, transcriptomic, histopathologic, and proteomic data relevant to cNF. Finally, we make recommendations for incorporating exploratory aims for predictive biomarkers into clinical trials through biobanking samples. CONCLUSION: These recommendations are intended to provide both researchers and clinicians with best practices for clinical trial design to aid in the identification of clinically validated biomarkers for cNF.

Stickler Syndrome: Airway Complications in a Case Series of 502 Patients.

BACKGROUND: Patients with Stickler syndrome often require emergency surgery and are often anesthetized in nonspecialist units, typically for retinal detachment repair. Despite the occurrence of cleft palate and Pierre-Robin sequence, there is little published literature on airway complications. Our aim was to describe anesthetic practice and complications in a nonselected series of Stickler syndrome cases. To our knowledge, this is the largest such series in the published literature. METHODS: We retrospectively identified patients with genetically confirmed Stickler syndrome who had undergone general anesthesia in a major teaching hospital, seeking to identify factors that predicted patients who would require more than 1 attempt to correctly site an endotracheal tube (ETT) or supraglottic airway device (SAD). Patient demographics, associated factors, and anesthetic complications were collected. Descriptive statistical analysis and logistic regression modeling were performed. RESULTS: Five hundred and twoanesthetic events were analyzed. Three hundred ninety-five (92.7%) type 1 Stickler and 63 (96.9%) type 2 Stickler patients could be managed with a single attempt of passing an ETT or SAD. Advanced airway techniques were required on 4 occasions, and we report no major complications. On logistic regression, modeling receding mandible (P = .0004) and history of cleft palate (P = .0004) were significantly associated with the need for more than 1 attempt at airway manipulation. CONCLUSIONS: The majority of Stickler patients can be anesthetized safely with standard management. If patients have a receding mandible or history of cleft, an experienced anesthetist familiar with Stickler syndrome should manage the patient. We recommend that patients identified to have a difficult airway wear an alert bracelet.

[Epiploic appendagitis: a rare cause of acute abdomen]. / Appendagite épiploïque: cause rare d'abdomen aigu.

Epiploic appendagitis is a rare cause of acute abdomen. It can mimic other inflammatory processes such as diverticulitis or appendicitis. Diagnosis is based on CT scan. Medical management is the approach of choice in the absence of complications.

Coexistence of Marfan-like Connective Tissue Disease with Morphologic Left Ventricular Non-compaction.

We treated a man with co-incident Marfan-like connective tissue disease with morphologic left ventricular non-compaction (LVNC). He underwent valve-sparing aortic root replacement because of aortic root dilation at 43 years old. Pathological findings of the aorta revealed cystic medio-necrosis, consistent with Marfan syndrome. He developed congestive heart failure caused by LVNC at 47 years old. His daughter had scoliosis, and he had several physical characteristics suggestive of Marfan syndrome. We herein report a rare case of a patient who had Marfan-like connective disease with an LVNC appearance.

Prevalence of Sagging Eye Syndrome in Adults with Binocular Diplopia.

PURPOSE: Sagging eye syndrome (SES), horizontal and/or vertical strabismus caused by orbital connective tissue degeneration, was first defined 10 years ago. This study investigated SES and other causes of acquired binocular diplopia in adults presenting to a single institution since the description of SES. DESIGN: Retrospective observational case series. METHODS: Medical records were reviewed of all new patients over the age of 40 who presented to the Stein Eye Institute with binocular diplopia between January 2015 and December 2018. Clinical causes of diplopia were tabulated in patients grouped by age and sex. In patients with SES, we tabulated binocular alignment, types of treatment, and surgical outcomes. RESULTS: There were 945 patients of mean age 66.5 years, of whom 514 (54.4%) were female. The most common cause of diplopia was SES (31.4%). The 297 patients with SES were older at 71.2 years (P < 0.0001) and more predominantly female at 59.9% than other patients (52.0%; P = 0.023). The relative proportion of SES patients among all diplopic patients increased with age from 4.7% under age 50 years to 60.9% over the age of 90. Age-related distance esotropia was present in 35% and cyclovertical strabismus in 65% of cases of SES. Strabismus surgery was performed in 50% of cases of SES. Mean esotropia at distance decreased from 6.9 ± 0.7Δ preoperatively to 0.3 ± 0.3Δ postoperatively. Preoperative hypertropia decreased from 3.0 ± 0.3Δ to 0.7 ± 0.2Δ postoperatively. Surgery resolved diplopia in all cases. CONCLUSIONS: It is important to recognize that SES is a very common cause of adult binocular diplopia.

Early and Late Results After David vs Bentall Procedure: A Propensity Matched Analysis.

BACKGROUND: The aim of this study was to compare the short- and long-term outcomes of patients who underwent aortic valve-sparing reimplantation (David) vs aortic root replacement (Bentall) operations in a propensity-matched analysis. METHODS: The study compared the data of propensity-matched patients who underwent David (n = 261) or Bentall (n = 262) procedures from 2000 to 2015. The mean age at surgery in the entire cohort was 53 ± 13 years, and 19.7% (n = 103) of the study patients were female. Connective tissue disease was present in 9.4% (n = 49) of patients, whereas 37.1% (n = 194) presented with a bicuspid aortic valve. RESULTS: The overall 30-day mortality was 1.1% (n = 6) and was not significantly different in patients with the David compared with the Bentall operation (0.4% [n = 1] vs 1.9% [n = 5]; P = .1). The 5- and 10-year survival rates were 93.7 ± 1.8% vs 93.8 ± 1.6% and 84.4 ± 4.7% vs 89.5 ± 3.2% for David vs Bentall, respectively (log-rank P = .98). Cox regression analysis identified age, smoking and previous cardiac surgery as independent predictors of long-term mortality. Freedom from reoperation did not significantly differ between patient groups (89.5 ± 3.4% vs 87.8 ± 4.1% 10 years postoperatively; log-rank P = .71). Bentall-treated patients had a higher rate of serious bleeding during follow-up (P = .025). CONCLUSIONS: Both the David and Bentall operations are associated with excellent early and long-term results in patients with aortic root aneurysmal disease. The David operation is associated with less bleeding than the Bentall operation, without an increased risk of reoperation. Because of avoidance of bleeding and other long-term complications associated with prosthetic heart valves, the David operation is preferable to the Bentall operation in patients with appropriate pathoanatomy.

Heart-lung transplantation: A viable option for connective tissue diseases.

BACKGROUND: While lung transplantation (LTx) has been effective for connective tissue disease (CTD) patients with pulmonary involvement, outcomes for heart-lung transplantation (HLTx) are less defined. The aim of this study is to evaluate HLTx in CTD patients utilizing the UNOS database. METHODS: HLTx patients with CTD (HLTx-CTD) were compared to both LTx patients with CTD (LTx-CTD) and HLTx patients with all other indications (HLTx-OI) from 1999 to 2018. Primary outcome was 1- and 5-year graft survival. Secondary outcomes included freedom from first-year rejection and outcomes prior to transplant discharge. RESULTS: 1143/29 323 adults received first-time HLTx or LTx for CTD. Seventeen were HLTx-CTD (3.3% of total HLTx) and 1126 were LTx-CTD (3.9% of total LTx). There were 492 HLTx-OI. Transplant hemodynamic values including cardiac output, pulmonary capillary wedge pressure, and calculated pulmonary vascular resistance were significantly worse for HLTx-CTD vs LTx-CTD (4.2 vs 5.4 L/min, P = .005; 14 vs 10 mm Hg, P = .009; 439 vs 267 dynes, P = .007, respectively). Cardiac status 1 was more common for HLTx-CTD vs HLTx-OI (94% vs 56%, P < .001). HLTx-CTD 1 and 5-year graft survival was similar compared to LTx-CTD and HLTx-OI. CONCLUSION: HLTx-CTD is a valid option for carefully selected patients with CTD cardiac and pulmonary involvement with similar morbidity and mortality compared to LTx-CTD and HLTx-OI.

Double-lung versus heart-lung transplantation for precapillary pulmonary arterial hypertension: a 24-year single-center retrospective study.

Transplant type for end-stage pulmonary vascular disease remains debatable. We compared recipient outcome after heart-lung (HLT) versus double-lung (DLT) transplantation. Single-center analysis (38 HLT-30 DLT; 1991-2014) for different causes of precapillary pulmonary hypertension (PH): idiopathic (22); heritable (two); drug-induced (nine); hepato-portal (one); connective tissue disease (four); congenital heart disease (CHD) (24); chronic thromboembolic PH (six). HLT decreased from 91.7% [1991-1995] to 21.4% [2010-2014]. Re-intervention for bleeding was higher after HLT; (P = 0.06) while primary graft dysfunction grades 2 and 3 occurred more after DLT; (P < 0.0001). Graft survival at 90 days, 1, 5, 10, and 15 years was 93%, 83%, 70%, 47%, and 35% for DLT vs. 82%, 74%, 61%, 48%, and 30% for HLT, respectively (log-rank P = 0.89). Graft survival improved over time: 100%, 93%, 87%, 72%, and 72% in [2010-2014] vs. 75%, 58%, 42%, 33%, and 33% in [1991-1995], respectively; P = 0.03. No difference in chronic lung allograft dysfunction (CLAD)-free survival was observed: 80% & 28% for DLT vs. 75% & 28% for HLT after 5 and 10 years, respectively; P = 0.49. Primary graft dysfunction in PH patients was lower after HLT compared to DLT. Nonetheless, overall graft and CLAD-free survival were comparable and improved over time with growing experience. DLT remains our preferred procedure for all forms of precapillary PH, except in patients with complex CHD.

Cervical medullary syndrome secondary to craniocervical instability and ventral brainstem compression in hereditary hypermobility connective tissue disorders: 5-year follow-up after craniocervical reduction, fusion, and stabilization.

A great deal of literature has drawn attention to the "complex Chiari," wherein the presence of instability or ventral brainstem compression prompts consideration for addressing both concerns at the time of surgery. This report addresses the clinical and radiological features and surgical outcomes in a consecutive series of subjects with hereditary connective tissue disorders (HCTD) and Chiari malformation. In 2011 and 2012, 22 consecutive patients with cervical medullary syndrome and geneticist-confirmed hereditary connective tissue disorder (HCTD), with Chiari malformation (type 1 or 0) and kyphotic clivo-axial angle (CXA) enrolled in the IRB-approved study (IRB# 10-036-06: GBMC). Two subjects were excluded on the basis of previous cranio-spinal fusion or unrelated medical issues. Symptoms, patient satisfaction, and work status were assessed by a third-party questionnaire, pain by visual analog scale (0-10/10), neurologic exams by neurosurgeon, function by Karnofsky performance scale (KPS). Pre- and post-operative radiological measurements of clivo-axial angle (CXA), the Grabb-Mapstone-Oakes measurement, and Harris measurements were made independently by neuroradiologist, with pre- and post-operative imaging (MRI and CT), 10/20 with weight-bearing, flexion, and extension MRI. All subjects underwent open reduction, stabilization occiput to C2, and fusion with rib autograft. There was 100% follow-up (20/20) at 2 and 5 years. Patients were satisfied with the surgery and would do it again given the same circumstances (100%). Statistically significant improvement was seen with headache (8.2/10 pre-op to 4.5/10 post-op, p < 0.001, vertigo (92%), imbalance (82%), dysarthria (80%), dizziness (70%), memory problems (69%), walking problems (69%), function (KPS) (p < 0.001). Neurological deficits improved in all subjects. The CXA average improved from 127° to 148° (p < 0.001). The Grabb-Oakes and Harris measurements returned to normal. Fusion occurred in 100%. There were no significant differences between the 2- and 5-year period. Two patients returned to surgery for a superficial wound infections, and two required transfusion. All patients who had rib harvests had pain related that procedure (3/10), which abated by 5 years. The results support the literature, that open reduction of the kyphotic CXA to lessen ventral brainstem deformity, and fusion/stabilization to restore stability in patients with HCTD is feasible, associated with a low surgical morbidity, and results in enduring improvement in pain and function. Rib harvest resulted in pain for several years in almost all subjects.

A Comparative Study of the Reverse Sural Fascio-Cutaneous Flap Outcomes in the Management of Foot and Ankle Soft Tissue Defects in Diabetic and Trauma Patients.

Introduction. Soft tissue defects in the distal leg and foot are challenging conditions for reconstruction. The widely used reverse sural fascio-cutaneous flap (RSFCF) has been reported with large variation in complication frequency. Some authors reported higher complications in the diabetic population when compared with trauma patients. We compared the reliability of the RSFCF in treating such defects among both populations. Methods. This is a retrospective series with a prospective data collection of 24 patients (11 with type 2 diabetes and 13 in trauma settings) treated with an ipsilateral RSFCF for soft tissue defects of the distal leg and the rear foot. Healing events and complications were recorded and compared for both groups. The mean follow-up was 32 months. Results. Diabetic group versus trauma group showed the following results; mean flap healing time of 24 versus 22 days, donor site healing time of 14 versus 16 days, 1 total flap necrosis in both groups, 3 versus 2 cases of skin edge necrosis, 2 cases of temporary venous congestion in both groups, and 8 versus 10 cases of transient hypoesthesia of the lateral border of the foot. No infection was encountered in both groups and no recurrence of infection in the primary infected diabetic patients. Conclusions. We found the RSFCF to be useful, reproducible, and reliable in treating soft tissue defects with a very low frequency of serious complications. Diabetic patients were found to have similar outcomes when compared with trauma patients. Therefore, diabetes might not be a major factor of flap failure. Levels of Evidence: Level III: Therapeutic.