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.

Efficacy and Safety of Exercise Testing and Rehabilitation for Aortic Dissection Patients: A SCOPING REVIEW.

OBJECTIVE: Although physical exercise has established benefits for long-term cardiovascular health, concern regarding further aortic events has limited the evidence for exercise among aortic dissection (AD) patients. The objective was to perform a scoping review of the current concepts and gaps in the literature regarding the benefit and safety of cardiovascular testing and rehabilitation among post-AD patients. REVIEW METHODS: A scoping review of the literature search was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR). Eligibility criteria included any studies with AD in relation to exercise rehabilitation or testing and physical or mental health. Electronic databases were queried for relevant studies (last queried, November 1, 2021). RESULTS: Six observational studies were included with a total of 381 patients with AD, all of whom underwent surgical intervention. Study heterogeneity prevented data synthesis and a formal systematic review, although four dominant themes emerged: cardiovascular-related outcomes, aorta-related outcomes, quality of life (QoL), and serious adverse events. Patients with AD have reduced baseline physical capacity and QoL. Rehabilitation programs may increase both physical status and QoL. Rates of serious adverse rates are minimal yet poorly defined. CONCLUSIONS: Within the context of apparent benefits from cardiovascular testing and rehabilitation for patients with AD who have undergone intervention, this scoping review highlights the need for increased comparative research specific to exercise among patients with AD and outcomes such as mortality and reinterventions.

[Stenting of uncomplicated type B aortic dissection].

Conservative treatment of uncomplicated type B aortic dissection is associated with low short-term mortality. However long-term mortality and complication rates are high, suggesting the need for more aggressive treatment. Studies suggest that combining medical treatment with thoracic endovascular aortic repair (TEVAR) is associated with a better prognosis. TEVAR is not without risk, however, and it is paramount to identify characteristics of risk and benefit as summarised in this review. Further studies are needed in order to implement improved patient selection.

Perigraft seroma penetrating the aortic sac and rupturing into the intraperitoneal cavity.

We present a case of a 66-year-old woman who developed perigraft seroma after having undergone elective, open abdominal aortic aneurysm repair with a polytetrafluoroethylene graft 5 years previously. One year after graft implantation, she started to suffer from abdominal discomfort and was therefore offered surgical intervention, which she declined owing to the fear of postoperative complications. Instead, an observational strategy was used. Five years later, the patient presented with sudden severe abdominal pain. Subsequent laparotomy revealed that the pseudomembrane lining the perigraft seroma had penetrated through the native aortic wall and into the intraperitoneal cavity, where it had ruptured. The patient was successfully treated by replacing the polytetrafluoroethylene graft with a polyethylene terephthalate (Dacron) graft.

Validation of contrast enhanced cine steady-state free precession and T2-weighted CMR for assessment of ischemic myocardial area-at-risk in the presence of reperfusion injury.

The purpose of the study was to validate by histopathology, contrast enhanced cine steady-state free precession and T2-weighted CMR for the assessment of ischemic myocardial area-at-risk (AAR) in the presence of microvascular obstruction (MVO). Eleven anesthetized pigs underwent CMR 7 to 10 days post infarction. The area-at-risk was measured from T2-weighted fast spin echo (T2-STIR) and contrast-enhanced steady-state free precession magnetic resonance imaging (CE-SSFP) images using semi-automated algorithms based on a priori knowledge of perfusion territory. Also, late gadolinium enhancement (LGE) was performed to measure final infarct size (FIS). Histopathological comparison with Evans blue dye to define AAR and triphenyltetrazolium chloride to define FIS served as the reference. All infarcts demonstrated MVO on LGE images. Bland-Altman analysis showed no significant bias in AAR or myocardial salvage between T2-STIR and CE-SSFP or between CMR and histopathology. The mean differences ± 2SD from Bland-Altman analysis were: AAR: Evans Blue vs. T2-STIR [0.7%; + 13.5%; - 12.1%]; AAR: Evans Blue vs. CE-SSFP [0.1%; + 13.8%; - 13.7%]; AAR: T2-STIR vs. CE-SSFP [0.7%; + 6.2%; - 4.9%]; Salvage: Evans Blue - TTC vs. T2-STIR-LGE [0.8%; + 11.1%; - 9.6%]; Salvage: Evans Blue - TTC vs. CE-SSFP-LGE [0.1%; + 9.9%; - 9.6%]; Salvage: CE-SSFP-LGE vs. T2-STIR-LGE [0.7%; + 6.2%; - 4.9%]. Both T2-STIR and CE-SSFP sequences allow for unbiased quantification of AAR in the presence of ischemia/reperfusion injury when analysed by semi-automated algorithms. These experimental data, which was validated by histopathology, supports the use of CMR for the assessment of myocardial salvage during the subacute phase.

Cardiovascular MR T2-STIR imaging does not discriminate between intramyocardial haemorrhage and microvascular obstruction during the subacute phase of a reperfused myocardial infarction.

OBJECTIVE: Microvascular obstruction (MVO) and intramyocardial haemorrhage (IMH) are known complications of myocardial ischaemia-reperfusion injury. Whereas MVO is an established marker for a poor clinical outcome, the clinical significance of IMH remains less well defined. Cardiovascular MR (CMR) and T2 weighted short tau inversion recovery (T2-STIR) imaging have been used to detect IMH and to explore its clinical importance. IMH is typically identified within the area-at-risk as a hypointense signal core on T2-STIR images. Because MVO will also appear as a hypointense signal core, T2-STIR imaging may not be an optimal method for assessing IMH. In this study, we sought to investigate the ability of T2-STIR to discriminate between MVO with IMH in a porcine myocardial ischaemia-reperfusion model that expressed MVO with and without IMH. METHOD: MVO with and without IMH (defined from both macroscopic evaluation and T1 weighted CMR) was produced in 13 pigs by a 65-min balloon occlusion of the mid left anterior descending artery, followed by reperfusion. Eight days after injury, all pigs underwent CMR imaging and subsequently the hearts were assessed by gross pathology. RESULTS: CMR identified MVO in all hearts. CMR and pathology showed that IMH was present in 6 of 13 (46%) infarcts. The sensitivity and specificity of T2-STIR hypointense signal core for identification of IMH was 100% and 29%, respectively. T2-values between hypointense signal core in the pigs with and without IMH were similar (60.4±3 ms vs 63.0±4 ms). CONCLUSIONS: T2-STIR did not allow identification of IMH in areas with MVO in a porcine model of myocardial ischaemic/reperfusion injury in the subacute phase of a reperfused myocardial infarction.

A novel FBN1 variant in a large Marfan family with high penetrance of aortic dissection or rupture.

INTRODUCTION: Marfan syndrome is an autosomal, dominantly inherited disorder of the connective tissue. We report the clinical data and results of a genetic analysis of a large Danish Marfan family. METHODS: Sanger sequencing of FBN1 was initially performed on genomic DNA from the index patient. Subsequently, four affected family members and three non-affected family members were tested for the variant identified in the index patient. RESULTS: A novel variant (c.701G>T) in the FBN1 segregated with Marfan features in the family. CONCLUSION: In the majority of the family members, this novel variant seems to cause a uniform and very detrimental set of disease characteristics including fatal aortic dissection. FUNDING: not relevant. TRIAL REGISTRATION: not relevant.

Imaging of carotid artery vessel wall edema using T2-weighted cardiovascular magnetic resonance.

BACKGROUND: Atherothrombosis remains a major health problem in the western world, and carotid atherosclerosis is an important contributor to embolic ischemic strokes. It remains a clinical challenge to identify rupture-prone atherosclerotic plaques before clinical events occur. Inflammation, endothelial injury and angiogenesis are features of vulnerable plaques and may all be associated with plaque edema. Therefore, vessel wall edema, which can be detected by 2D T2-weighted cardiovascular magnetic resonance (CMR), may be used as a dynamic marker of disease activity in the atherosclerotic plaque. However, 2D imaging is limited by low spatial resolution in the slice-select direction compared to 3D imaging techniques. We sought to investigate the ability of novel 3D techniques to detect edema induced in porcine carotid arteries by acute balloon injury compared to conventional 2D T2-weighted black-blood CMR. METHODS: Edema was induced unilaterally by balloon overstretch injury in the carotid artery of nine pigs. Between one to seven hours (average four hours) post injury, CMR was performed using 2D T2-weighted short-tau inversion recovery (T2-STIR), 3D volumetric isotropic turbo spin echo acquisition (VISTA) and 3D T2 prepared gradient-echo (T2prep-GE). The CMR images were compared in terms of signal-to-noise ratio (SNR) and contrast-to-noise (CNR) ratio. Furthermore, the presence of vessel wall injury was validated macroscopically by means of Evans Blue dye that only enters the injured vessel wall. RESULTS: All three imaging sequences classified the carotid arteries correctly compared to Evans Blue and all sequences demonstrated a significant increase in SNR of the injured compared to the non-injured carotid vessel wall (T2-STIR, p = 0.002; VISTA, p = 0.004; and T2prep-GE, p = 0.003). There was no significant difference between sequences regarding SNR and CNR. CONCLUSION: The novel 3D imaging sequences VISTA and T2prep-GE perform comparably to conventional 2D T2-STIR in terms of detecting vessel wall edema. The improved spatial coverage of these 3D sequences may facilitate visualization of vessel wall edema to enable detection and monitoring of vulnerable carotid atherosclerotic plaques.

Assessment of intramyocardial hemorrhage by T1-weighted cardiovascular magnetic resonance in reperfused acute myocardial infarction.

BACKGROUND: Intramyocardialhemorrhage (IMH) reflects severe reperfusion injury in acute myocardial infarction. Non-invasive detection of IMH by cardiovascular magnetic resonance (CMR) may serve as a surrogate marker to evaluate the effect of preventive measures to reduce reperfusion injury and hence provide additional prognostic information. We sought to investigate whether IMH could be detected by CMR exploiting the T1 shortening effect of methemoglobin in an experimental model of acute myocardial infarction. The results were compared to T2-weighthed short tau inversion recovery (T2-STIR), and T2*-weighted(T2*W) sequences. METHODS AND RESULTS: IMH was induced in ten 40 kg pigs by 50-min balloon occlusion of the mid LAD followed by reperfusion. Between 4-9 days (average 4.8) post-injury, the left ventricular myocardium was assessed by T1-weigthed Inversion Recovery(T1W-IR), T2-STIR, and T2*W sequences. All CMR images were matched to histopathology and compared with the area of IMH. The difference between the size of the IMH area detected on T1W-IR images and pathology was -1.6 ± 11.3% (limits of agreement, -24%-21%), for the T2*W images the difference was -0.1 ± 18.3% (limits of agreement, -36.8%-36.6%), and for T2-STIR the difference was 8.0 ± 15.5% (limits of agreement, -23%-39%). By T1W IR the diagnostic sensitivity of IMH was 90% and specificity 70%, for T2*W imaging the sensitivity was 70% and specificity 50%, and for T2-STIR sensitivity for imaging IMH was 50% and specificity 60%. CONCLUSION: T1-weigthed non-contrast enhanced CMR detects IMH with high sensitivity and specificity and may become a diagnostic tool for detection of IMH in patients with myocardial infarction.

Measuring myocardial salvage.

The efficacy of cardioprotective strategies can be quantified by myocardial salvage as an indicator of therapeutic benefit. Salvage is calculated as the difference between the area at risk (AAR) and the final infarct size (FIS). AAR has been quantified by angiographic assessment followed by quantification of FIS by biochemical ischaemic markers or imaging modalities such as cardiovascular magnetic resonance (CMR). Angiographical methods may overestimate AAR and since methodological differences may exist between different modalities, the use of different modalities for estimating AAR and FIS may not be recommended. (99m)Technetium (Tc)-Sestamibi single-photon emission tomography (SPECT) allows quantification of AAR and FIS by tracer injection prior to revascularization and after 1 month, respectively. SPECT provides the most validated measure of myocardial salvage and has been utilized in multiple randomized clinical trials. However, SPECT is logistically challenging, expensive, and includes radiation exposure. More recently, a large number of studies have suggested that CMR can determine salvage in a single examination by combining measures of myocardial oedema in the AAR exposed to ischaemia reperfusion with FIS quantification by late gadolinium enhancement. The T1- and T2-weighted CMR approaches for quantification of AAR utilize non-contrast, early and late gadolinium enhancement techniques. The technical progress, high spatial resolution and the potential for retrospective quantification of the AAR makes CMR the most appropriate technique for assessment of myocardial salvage. However, the optimum CMR technique for assessment of myocardial AAR remains to be defined. Consequently, we recommend a comprehensive CMR protocol to ensure reliable assessment of myocardial salvage.

Determination of acute vascular injury and edema in porcine carotid arteries by T2 weighted cardiovascular magnetic resonance.

Inflammation plays an essential role for destabilization and rupture of carotid atherosclerotic plaques causing embolic ischemic stroke. Inflammation of the vessel wall may result in the formation of edema. This study investigated whether edema in the carotid artery wall induced by acute balloon injury could be detected by cardiovascular magnetic resonance (CMR) using a T2-weighted short-tau inversion recovery sequence (T2-STIR). Edema was induced unilaterally by balloon injury in the carotid artery of six pigs. Four to nine days (average six) post injury, the carotid arteries were assessed by T2-STIR and multi-contrast weighted sequences. CMR images were matched to histopathology, validated against Evans blue, and correlated with the amount of fibrinogen in the arterial wall used as an edema marker. T2-STIR images showed that the carotid signal intensity (SI) divided by the sternocleid muscle SI of the injured carotid artery was on average 223% (P = 0.03) higher than that of the uninjured carotid artery. Using a threshold value of 4SD, T2-STIR detected edema in the vessel wall (i.e., hyperintense signal intensity) with a sensitivity of 100% and a specificity of 75%. Agreement was observed between carotid artery wall hyperintense signal intensity and Evans blue uptake (X(2) = 17.1, P < 0.001). The relative signal intensity correlated in a linear fashion with the amount of fibrinogen detected by histopathology (ρ = 0.9, P < 0.001). None of the multi-contrast weighted sequences detected edema in the carotid artery with reasonable sensitivity or specificity. T2-STIR CMR allowed carotid artery wall edema detection and may therefore be a useful non-invasive diagnostic tool for determination of inflammatory activity in the carotid artery wall.

Determination of edema in porcine coronary arteries by T2 weighted cardiovascular magnetic resonance.

BACKGROUND: Inflammation plays a pivotal role in all stages of atherosclerosis. Since edema is known to be an integral part of inflammation, a noninvasive technique that can identify edema in the coronary artery wall may provide unique information regarding plaque activity. In this study, we aimed to determine whether edema induced in porcine coronary arteries by balloon injury could be reliably detected by cardiovascular magnetic resonance (CMR) using a water sensitive T2-weighted short tau inversion recovery sequence (T2-STIR). We also aimed to compare these results to those of conventional T2-weighted (T2W) imaging. METHODS: Edema was induced in the proximal left anterior descending (LAD) coronary artery wall in seven pigs by balloon injury. At baseline, and 1-10 days (average four) post injury, the proximal LAD was assessed by water sensitive T2-STIR and conventional T2W sequences in cross-sectional planes. CMR images were matched to histopathology, validated against Evans blue as a marker of increased vessel wall permeability, and correlated with the arterial amount of fibrinogen used as an edema surrogate marker. RESULTS: Post injury, the T2-STIR images of the injured LAD vessel wall showed a significant 72%, relative signal intensity (SI) increase compared with baseline (p = 0.028). Using a threshold value of SI 7 SD above the average SI of the myocardium, T2-STIR detected edema in the vessel wall (i.e. enhancement) with a sensitivity of 100 and a specificity of 71. Twelve out of the 14 (86%) T2-STIR images displaying coronary artery wall enhancement also showed Evans blue uptake in the corresponding histology. The relative signal intensity showed a linear correlation with the amount of fibrinogen detected on the corresponding histopathology (ρ = 0.750, p = 0.05). The conventional T2W images did not show significant changes in SI post injury. CONCLUSION: T2-STIR CMR enabled detection of coronary artery wall edema and could therefore be a non-invasive diagnostic tool for evaluation of inflammatory coronary artery wall activity.

In vivo evaluation and proof of radiofrequency safety of a novel diagnostic MR-electrophysiology catheter.

An MR-electrophysiology (EP) catheter is presented that provides full diagnostic EP functionality and a high level of radiofrequency safety achieved by custom-designed transmission lines. Highly resistive wires transmit intracardiac electrograms and currents for intracardiac pacing. A transformer cable transmits the localization signal of a tip coil. Specific absorption rate simulations and temperature measurements at 1.5 T demonstrate that a wire resistance > 3 kΩ/m limits dielectric heating to a physiologically irrelevant level. Additional wires do not increase tip specific absorption rate significantly, which is important because some clinical catheters require up to 20 electrodes. It is further demonstrated that radiofrequency-induced and pacing-induced resistive heating of the wires is negligible under clinical conditions. The MR-EP catheters provided uncompromised recording of electrograms and cardiac pacing in combination with a standard EP recorder in MR-guided in vivo EP studies, and the tip coil enabled fast and robust catheter localization. In vivo temperature measurements during such a study did not detect any device-related heating, which confirms the high level of safety of the catheter, whereas unacceptable heating was found with a standard EP catheter. The presented concept for the first time enables catheters with full diagnostic EP functionality and active tracking and at the same time a sufficient level of radiofrequency safety for MRI without specific absorption rate-related limitations.

Utilizing different methods for visualizing susceptibility from a single multi-gradient echo dataset.

PURPOSE: Objects that cause a susceptibility gradient can generate regions of hypo-intensity in MRI. MR techniques developed for positive enhancement of such objects require sequence parameter optimization. Thus comparison of images acquired successively using different techniques is difficult since different parameter settings result in variations in signal and noise. A new method is presented that allows production of positive contrast images, a relaxation rate R*2-map and negative contrast images from a single dataset by post-processing. METHODS: Positive contrast techniques considered include the "white marker" technique, inversion-recovery on-resonance (IRON) and susceptibility gradient mapping (SGM). The new method was tested in phantoms of iron-oxide agent gel solutions and prostate marker seeds. Images produced by post-processing were compared with those obtained directly. The post-processing technique was applied in vivo for the visualization of iron-oxide contrast agent uptake in a balloon-injured swine carotid model. RESULTS: The images produced in the post-processing step allowed determination of optimal parameter settings for each technique. SGM was found to provide the greatest positive contrast, whilst the T*2-weighted images provide more sensitivity to regions that exhibited weaker susceptibility effects. CONCLUSIONS: Combined T*2-weighted imaging and SGM using the same complex image data was found to provide complementary information and high sensitivity to detect distortion inducing agents.