Rossella Fattori

Nonsurgical reconstruction of thoracic aortic dissection by stent-graft placement.

BACKGROUND The treatment of thoracic aortic dissection is guided by prognostic and anatomical information. Proximal dissection requires surgery, but the appropriate treatment of distal thoracic aortic dissection has not been determined, because surgery has failed to improve the prognosis. METHODS We prospectively evaluated the safety and efficacy of elective transluminal endovascular stent-graft insertion in 12 consecutive patients with descending (type B) aortic dissection and compared the results with surgery in 12 matched controls. In all 24 patients, aortic dissection was diagnosed by magnetic resonance angiography. In each group, the dissection involved the aortic arch in 3 patients and the descending thoracic aorta in all 12 patients. With the patient under general anesthesia, either surgical resection was undertaken or a custom-designed endovascular stent-graft was placed by unilateral arteriotomy. RESULTS Stent-graft placement resulted in no morbidity or mortality, whereas surgery for type B dissection was associated with four deaths (33 percent, P=0.09) and five serious adverse events (42 percent, P=0.04) within 12 months. Transluminal placement of the stent-graft prosthesis was successful in all patients, with no leakage; full expansion of the stents was ensured by balloon inflation at 2 to 3 atm. Sealing of the entry tear was monitored during the procedure by transesophageal ultrasonography and angiography, and thrombosis of the false lumen was confirmed in all 12 patients after a mean of three months by magnetic resonance imaging. There were no deaths or instances of paraplegia, stroke, embolization, side-branch occlusion, or infection in the stent-graft group; nine patients had postimplantation syndrome, with transient elevation of C-reactive protein levels and body temperature plus mild leukocytosis. All the patients who received stent-grafts recovered, as did seven patients who underwent surgery for type B dissection (58 percent) (P=0.04). CONCLUSIONS These preliminary observations suggest that elective, nonsurgical insertion of an endovascular stent-graft is safe and efficacious in selected patients who have thoracic aortic dissection and for whom surgery is indicated. Endoluminal repair may be useful for interventional reconstruction of thoracic aortic dissection.

Long-term survival in patients presenting with type B acute aortic dissection: Insights from the international registry of acute aortic dissection

Background— Follow-up survival studies in patients with acute type B aortic dissection have been restricted to a small number of patients in single centers. We used data from a contemporary registry of acute type B aortic dissection to better understand factors associated with adverse long-term survival. Methods and Results— We examined 242 consecutive patients discharged alive with acute type B aortic dissection enrolled in the International Registry of Acute Aortic Dissection (IRAD) between 1996 and 2003. Kaplan-Meier survival curves were constructed, and Cox proportional hazards analysis was performed to identify independent predictors of follow-up mortality. Three-year survival for patients treated medically, surgically, or with endovascular therapy was 77.6±6.6%, 82.8±18.9%, and 76.2±25.2%, respectively (median follow-up 2.3 years, log-rank P=0.61). Independent predictors of follow-up mortality included female gender (hazard ratio [HR], 1.99; 95% confidence interval [CI], 1.07 to 3.71; P=0.03), a history of prior aortic aneurysm (HR, 2.17; 95% CI, 1.03 to 4.59; P=0.04), a history of atherosclerosis (HR, 2.48; 95% CI, 1.32 to 4.66; P<0.01), in-hospital renal failure (HR, 2.55; 95% CI, 1.15 to 5.63; P=0.02), pleural effusion on chest radiograph (HR, 2.56; 95% CI, 1.18 to 5.58; P=0.02), and in-hospital hypotension/shock (HR, 12.5; 95% CI, 3.24 to 48.21; P<0.01). Conclusions— Contemporary follow-up mortality in patients who survive to hospital discharge with acute type B aortic dissection is high, approaching 1 in every 4 patients at 3 years. Current treatment and follow-up surveillance require further study to better understand and optimize care for patients with this complex disease.

Randomized comparison of strategies for type B aortic dissection: the INvestigation of STEnt Grafts in Aortic Dissection (INSTEAD) trial.

Background— Thoracic endovascular aortic repair (TEVAR) represents a novel concept for type B aortic dissection. Although life-saving in acute emergencies, outcomes and survival of TEVAR in stable dissection are unknown. Methods and Results— One hundred forty patients in stable clinical condition at least 2 weeks after index dissection were randomly subjected to elective stent-graft placement in addition to optimal medical therapy (n=72) or to optimal medical therapy alone (n=68) with surveillance (arterial pressure according to World Health Organization guidelines ≤120/80 mm Hg). The primary end point was all-cause death at 2 years, whereas aorta-related death, progression (with need for conversion or additional endovascular or open surgery), and aortic remodeling were secondary end points. There was no difference in all-cause deaths, with a 2-year cumulative survival rate of 95.6±2.5% with optimal medical therapy versus 88.9±3.7% with TEVAR (P=0.15); the trial, however, turned out to be underpowered. Moreover, the aorta-related death rate was not different (P=0.44), and the risk for the combined end point of aorta-related death (rupture) and progression (including conversion or additional endovascular or open surgery) was similar (P=0.65). Three neurological adverse events occurred in the TEVAR group (1 paraplegia, 1 stroke, and 1 transient paraparesis), versus 1 case of paraparesis with medical treatment. Finally, aortic remodeling (with true-lumen recovery and thoracic false-lumen thrombosis) occurred in 91.3% of patients with TEVAR versus 19.4% of those who received medical treatment (P<0.001), which suggests ongoing aortic remodeling. Conclusions— In the first randomized study on elective stent-graft placement in survivors of uncomplicated type B aortic dissection, TEVAR failed to improve 2-year survival and adverse event rates despite favorable aortic remodeling. Clinical Trial Registration— URL: http://www.clinicaltrials.gov. Unique identifier: NCT00525356.

Aortic Diameter ≥5.5 cm Is Not a Good Predictor of Type A Aortic Dissection Observations From the International Registry of Acute Aortic Dissection (IRAD)

Background— Studies of aortic aneurysm patients have shown that the risk of rupture increases with aortic size. However, few studies of acute aortic dissection patients and aortic size exist. We used data from our registry of acute aortic dissection patients to better understand the relationship between aortic diameter and type A dissection. Methods and Results— We examined 591 type A dissection patients enrolled in the International Registry of Acute Aortic Dissection between 1996 and 2005 (mean age, 60.8 years). Maximum aortic diameters averaged 5.3 cm; 349 (59%) patients had aortic diameters <5.5 cm and 229 (40%) patients had aortic diameters <5.0 cm. Independent predictors of dissection at smaller diameters (<5.5 cm) included a history of hypertension (odds ratio, 2.17; 95% confidence interval, 1.03 to 4.57; P=0.04), radiating pain (odds ratio, 2.08; 95% confidence interval, 1.08 to 4.0; P=0.03), and increasing age (odds ratio, 1.03; 95% confidence interval, 1.00 to 1.05; P=0.03). Marfan syndrome patients were more likely to dissect at larger diameters (odds ratio, 14.3; 95% confidence interval, 2.7 to 100; P=0.002). Mortality (27% of patients) was not related to aortic size. Conclusions— The majority of patients with acute type A acute aortic dissection present with aortic diameters <5.5 cm and thus do not fall within current guidelines for elective aneurysm surgery. Methods other than size measurement of the ascending aorta are needed to identify patients at risk for dissection.

Acute Intramural Hematoma of the Aorta A Mystery in Evolution

Background—The definition, prevalence, outcomes, and appropriate treatment strategies for acute intramural hematoma (IMH) continue to be debated. Methods and Results—We studied 1010 patients with acute aortic syndromes who were enrolled in the International Registry of Aortic Dissection (IRAD) to delineate the prevalence, presentation, management, and outcomes of acute IMH by comparing these patients with those with classic aortic dissection (AD). Fifty-eight (5.7%) patients had IMH, and this cohort tended to be older (68.7 versus 61.7 years; P<0.001) and more likely to have distal aortic involvement (60.3% versus 35.3%; P<0.001) compared with 952 patients with AD. Patients with IMH described more severe initial pain than did those with AD but were less likely to have ischemic leg pain, pulse deficits, or aortic valve insufficiency; moreover, they required a longer time to diagnosis and more diagnostic tests. Overall mortality of IMH was similar to that of classic AD (20.7% versus 23.9%; P=0.57), as was mortality in patients with IMH of the descending aorta (8.3% versus 13.1%; P=0.60) and the ascending aorta (39.1% versus 29.9%; P=0.34) compared with AD. IMH limited to the aortic arch was seen in 7 patients, with no deaths, despite medical therapy in only 6 of the 7 individuals. Among the 51 patients whose initial diagnostic study showed IMH only, 8 (16%) progressed to AD on a serial imaging study. Conclusions—The IRAD data demonstrate a 5.7% prevalence of IMH in patients with acute aortic syndromes. Like classic AD, IMH is a highly lethal condition when it involves the ascending aorta and surgical therapy should be considered, but this condition is less critical when limited to the arch or descending aorta. Fully 16% of patients have evidence of evolution to dissection on serial imaging.

Drug-eluting stents in vascular intervention

CONTEXT Restenosis is the most important long-term limitation of stent implantation for coronary artery disease, occurring in 15-60% of patients. In-stent restenosis, a refractory coronary lesion resulting from neointimal hyperplasia, challenges both vascular biologist and interventional cardiologist. Various drugs and devices have been used tried to overcome restenosis but are not particularly successful. Over 1500000 percutaneous coronary interventions are done annually. Restenosis is not only important clinically but also for its impact on health-care costs. STARTING POINT Growth and migration of vascular smooth-muscle cells result in neointimal proliferation after vascular injury and are the key mechanism of in-stent restenosis. The rationale of the most recent approaches to restenosis (eg, brachytherapy and immunosuppressive agents) arises from the similarity between tumour-cell growth and the benign tissue proliferation which characterises intimal hyperplasia. Several immunosuppressants have been tested for their potential to inhibit restenosis, with the novel strategy of administering the drug via a coated stent platform. Local drug delivery achieves higher tissue concentrations of drug without systemic effects, at a precise site and time. The first multicentre trial with stents coated with sirolimus was by Marie-Claude Morice and colleagues (N Engl J Med 2002; 346: 1773-80). In a trial of 238 patients, restenosis of 50% or more at 6 months was 0% and 27% with sirolimus or normal stents (p<0.001), respectively, after percutaneous revascularisation. Muzaffer Degertekin and colleagues (Circulation 2002; 106: 1610-13) present data on 2-year follow-up of 15 patients who had been implanted with the sirolimus stent in another study, and confirm persistent inhibition of restenosis and an absence of unexpected adverse events. WHERE NEXT? Local application of antiproliferative agents is a promising technique and research is developing. Other agents with potential benefits (eg, statins, local gene-therapy, adenovirus-mediated arterial gene-transfer, L-arginine, abciximab, angiopeptin, recombinant pegylated hirudin, and hiloprost) as well as improvements in polymer technology (biodegradable smart polymers, coatings for multiple-drug release) are under evaluation. The clinical impact of the elimination of restenosis may influence the approach to coronary artery disease, the future of cardiac surgery, and health-care economics in cardiology.

Endovascular Repair of Type B Aortic Dissection Long-term Results of the Randomized Investigation of Stent Grafts in Aortic Dissection Trial

Background—Thoracic endovascular aortic repair (TEVAR) represents a therapeutic concept for type B aortic dissection. Long-term outcomes and morphology after TEVAR for uncomplicated dissection are unknown. Methods and Results—A total of 140 patients with stable type B aortic dissection previously randomized to optimal medical treatment and TEVAR (n=72) versus optimal medical treatment alone (n=68) were analyzed retrospectively for aorta-specific, all-cause outcomes, and disease progression using landmark statistical analysis of years 2 to 5 after index procedure. Cox regression was used to compare outcomes between groups; all analyses are based on intention to treat. The risk of all-cause mortality (11.1% versus 19.3%; P=0.13), aorta-specific mortality (6.9% versus 19.3%; P=0.04), and progression (27.0% versus 46.1%; P=0.04) after 5 years was lower with TEVAR than with optimal medical treatment alone. Landmark analysis suggested a benefit of TEVAR for all end points between 2 and 5 years; for example, for all-cause mortality (0% versus 16.9%; P=0.0003), aorta-specific mortality (0% versus 16.9%; P=0.0005), and for progression (4.1% versus 28.1%; P=0.004); Landmarking at 1 year and 1 month revealed consistent findings. Both improved survival and less progression of disease at 5 years after elective TEVAR were associated with stent graft induced false lumen thrombosis in 90.6% of cases (P<0.0001). Conclusions—In this study of survivors of type B aortic dissection, TEVAR in addition to optimal medical treatment is associated with improved 5-year aorta-specific survival and delayed disease progression. In stable type B dissection with suitable anatomy, preemptive TEVAR should be considered to improve late outcome. Clinical Trial Registration—URL: http://www.clinicaltrials.gov. Unique identifier: NCT01415804.

Complicated Acute Type B Dissection: Is Surgery Still the Best Option?: A Report From the International Registry of Acute Aortic Dissection

OBJECTIVES Impact on survival of different treatment strategies was analyzed in 571 patients with acute type B aortic dissection enrolled from 1996 to 2005 in the International Registry of Acute Aortic Dissection. BACKGROUND The optimal treatment for acute type B dissection is still a matter of debate. METHODS Information on 290 clinical variables were compared, including demographics; medical history; clinical presentation; physical findings; imaging studies; details of medical, surgical, and endovascular management; in-hospital clinical events; and in-hospital mortality. RESULTS Of the 571 patients with acute type B aortic dissection, 390 (68.3%) were treated medically, 59 (10.3%) with standard open surgery and 66 (11.6%) with an endovascular approach. Patients who underwent emergency endovascular or open surgery were younger (mean age 58.8 years, p < 0.001) than their counterparts treated conservatively, and had male preponderance and hypertension in 76.9%. Patients submitted to surgery presented with a wider aortic diameter than patients treated by interventional techniques or by medical therapy (5.36 +/- 1.7 cm vs. 4.62 +/- 1.4 cm vs. 4.47 +/- 1.4 cm, p = 0.003). In-hospital complications occurred in 20% of patients subjected to endovascular technique and in 40% of patients after open surgical repair. In-hospital mortality was significantly higher after open surgery (33.9%) than after endovascular treatment (10.6%, p = 0.002). After propensity and multivariable adjustment, open surgical repair was associated with an independent increased risk of in-hospital mortality (odds ratio: 3.41, 95% confidence interval: 1.00 to 11.67, p = 0.05). CONCLUSIONS In the International Registry of Acute Aortic Dissection, the less invasive nature of endovascular treatment seems to provide better in-hospital survival in patients with acute type B dissection; larger randomized trials or comprehensive registries are needed to access impact on outcomes.

Gender-Related Differences in Acute Aortic Dissection

Background—Few data exist on gender-related differences in clinical presentation, diagnostic findings, management, and outcomes in acute aortic dissection (AAD). Methods and Results—Accordingly, we evaluated 1078 patients enrolled in the International Registry of Acute Aortic Dissection (IRAD) to assess differences in clinical features, management, and in-hospital outcomes between men and women. Of the patients enrolled in IRAD (32.1%) with AAD, 346 were women. Although less frequently affected by AAD (32.1% of AAD), women were significantly older and had more often presented later than men (P =0.008); symptoms of coma/altered mental status were more common, whereas pulse deficit was less common. Diagnostic imaging suggestive of rupture, ie, periaortic hematoma, and pleural or pericardial effusion were more commonly observed in women. In-hospital complications of hypotension and tamponade occurred with greater frequency in women, resulting in higher in-hospital mortality compared with men. After adjustment for age and hypertension, women with aortic dissection die more frequently than men (OR, 1.4, P =0.04), predominantly in the 66- to 75-year age group. Moreover, surgical outcome was worse in women than men (P =0.013); type A dissection in women was associated with a higher surgical mortality of 32% versus 22% in men despite similar delay, surgical technique, and hemodynamics. Conclusions—Our analysis provides insights into gender-related differences in AAD with regard to clinical characteristics, management, and outcomes; important diagnostic and therapeutic implications may help shed light on aortic dissection in women to improve their outcomes.

Choice of computed tomography, transesophageal echocardiography, magnetic resonance imaging, and aortography in acute aortic dissection: International Registry of Acute Aortic Dissection (IRAD).

For acute aortic dissection, CT is selected most frequently worldwide as the initial test, followed by TEE. Aortography and MRI are performed much less often. More than two thirds of the patients required ≥2 imaging tests.