Hüseyin Ince

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.

Preservation from left ventricular remodeling by front-integrated revascularization and stem cell liberation in evolving acute myocardial infarction by use of granulocyte-colony-stimulating factor (FIRSTLINE-AMI)

Background— Considering experimental evidence that stem cells enhance myocardial regeneration and granulocyte colony–stimulating factor (G-CSF) mediates mobilization of CD34+ mononuclear blood stem cells (MNCCD34+), we tested the impact of G-CSF integrated into primary percutaneous coronary intervention (PCI) management of acute myocardial infarction in man. Methods and Results— Fifty consecutive patients with ST-segment elevation myocardial infarction were subjected to primary PCI stenting with abciximab and followed up for 6 months; 89±35 minutes after successful PCI, 25 patients were randomly assigned in this pilot study (PROBE design) to receive subcutaneous G-CSF at 10 &mgr;g/kg body weight for 6 days in addition to standard care, including aspirin, clopidogrel, an ACE inhibitor, &bgr;-blocking agents, and statins. By use of CellQuest software on peripheral blood samples incubated with CD45 and CD34, mobilized MNCCD34+ were quantified on a daily basis. With homogeneous demographics and clinical and infarct-related characteristics, G-CSF stimulation led to mobilization of MNCCD34+ to between 3.17±2.93 MNCCD34+/&mgr;L at baseline and 64.55±37.11 MNCCD34+/&mgr;L on day 6 (P<0.001 versus control); there was no indication of leukocytoclastic effects, significant pain, impaired rheology, inflammatory reactions, or accelerated restenosis at 6 months. Within 35 days, G-CSF and MNCCD34+ liberation led to enhanced resting wall thickening in the infarct zone of between 0.29±0.22 and 0.99±0.32 mm versus 0.49±0.29 mm in control subjects (P<0.001); under inotropic challenge with dobutamine (10 &mgr;g · kg−1 · min−1), wall motion score index showed improvement from 1.66±0.23 to 1.41±0.21 (P<0.004 versus control) and to 1.35±0.24 after 4 months (P<0.001 versus control), respectively, coupled with sustained recovery of wall thickening to 1.24±0.31 mm (P<0.001 versus control) at 4 months. Accordingly, resting wall motion score index improved with G-CSF to 1.41±0.25 (P<0.001 versus control), left ventricular end-diastolic diameter to 55±5 mm (P<0.002 versus control), and ejection fraction to 54±8% (P<0.001 versus control) after 4 months. Morphological and functional improvement with G-CSF was corroborated by enhanced metabolic activity and 18F-deoxyglucose uptake in the infarct zone (P<0.001 versus control). Conclusions— G-CSF and mobilization of MNCCD34+ after reperfusion of infarcted myocardium may offer a pragmatic strategy for preservation of myocardium and prevention of remodeling without evidence of aggravated restenosis.

Prevention of left ventricular remodeling with granulocyte colony-stimulating factor after acute myocardial infarction: Final 1-year results of the front-integrated revascularization and stem cell liberation in evolving acute myocardial infarction by granulocyte colony-stimulating factor (FIRSTLINE-AMI) trial

Background—Experimental and clinical evidence has recently shown that pluripotent stem cells can be mobilized by granulocyte colony-stimulating factor (G-CSF) and may enhance myocardial regeneration early after primary percutaneous coronary intervention (PCI) management of acute myocardial infarction. Sustained or long-term effects of mobilized CD34-positive mononuclear stem cells, however, are unknown. Methods and Results—Thirty consecutive patients with ST-elevation myocardial infarction undergoing primary PCI with stenting and abciximab were selected for the study 85±30 minutes after PCI; 15 patients were randomly assigned to receive subcutaneous G-CSF at 10 &mgr;g/kg body weight for 6 days in addition to standard care including aspirin, clopidogrel, an angiotensin-converting enzyme inhibitor, β-blocking agents, and statins. In patients with comparable demographics and clinical and infarct-related characteristics, G-CSF stimulation led to sustained mobilization of CD34 positive mononuclear cells (MNCCD34+), with a 20-fold increase (from 3±2 at baseline to 66±54 MNCCD34+/&mgr;L on day 6; P<0.001); there was no evidence of leukocytoclastic effects, accelerated restenosis rate, or any late adverse events. Within 4 months, G-CSF–induced MNCCD34+ mobilization led to enhanced resting wall thickening in the infarct zone of 1.16±0.29 mm (P<0.05 versus control), which was sustained at 1.20±0.28 after 12 months (P<0.001 versus control). Similarly, left ventricular ejection fraction improved from 48±4% at baseline to 54±8% at 4 months (P<0.005 versus control) and 56±9% at 12 months (P<0.003 versus control and paralleled by sustained improvement of wall-motion score index from 1.70±0.22 to 1.42±0.26 and 1.33±0.21 at 4 and 12 months, respectively), after G-CSF (P<0.05 versus baseline and P<0.03 versus controls). Accordingly, left ventricular end-diastolic diameter showed no remodeling and stable left ventricular dimensions after G-CSF stimulation, whereas left ventricular end-diastolic diameter in controls revealed enlargement from 55±4 mm at baseline to 58±4 mm (P<0.05 versus baseline) at 12 months after infarction and no improvement in diastolic function. Conclusion—Mobilization of MNCCD34+ by G-CSF after primary PCI may offer a pragmatic strategy for improvement in ventricular function and prevention of left ventricular remodeling 1 year after acute myocardial infarction.

Intentional occlusion of the left subclavian artery during stent-graft implantation in the thoracic aorta: risk and relevance.

Purpose: To examine the clinical consequences and/or potential need for postinterventional transposition after stent-graft occlusion of the left subclavian artery (LSA). Methods: The records of 171 consecutive patients (128 men; mean age 60.2±13.2 years, range 20–83) undergoing elective stent-graft repair in the thoracic aorta were reviewed to identify intentional endograft coverage of the ostial LSA, as documented by transesophageal echocardiography and/or aortography. Patients were treated for subacute type B dissection, true aneurysm, pseudoaneurysm, or previously operated type A dissection with persistent false lumen flow in the descending aorta. Among the 171 cases, 22 (12.9%) patients were identified with stent-graft occlusion of the LSA. Results: A systolic blood pressure differential existed between the right (138.4±14.0 mmHg) and the left (101.8±21.0 mmHg; p<0.05) arms after occlusion of the LSA. No patient showed a malperfusion syndrome during postinterventional hospitalization. During a mean follow-up of 24.0±15.8 months, 15 (68.2%) patients remained completely asymptomatic, with no functional deficit or temperature differential between the arms, while 7 patients reported mild symptoms of a subclavian steal syndrome. However, no patient required any secondary surgical intervention. Conclusions: Stent-graft—induced occlusion of the ostial LSA was tolerated by all patients without chronic functional deficit. In the absence of stenotic vertebral and/or carotid arteries and with a documented intact vertebrobasilar system, prophylactic transposition of the LSA is not required prior to intentional stent-graft occlusion of the LSA.

Provisional extension to induce complete attachment after stent-graft placement in type B aortic dissection: the PETTICOAT concept.

Purpose: To report the use of a technique (PETTICOAT: provisional extension to induce complete attachment) to obliterate sustained abdominal false lumen flow and pressurization despite successful stent-graft sealing of the thoracic entry tear in patients with complicated type B aortic dissection. Methods: Of 100 initial patients subjected to stent-graft repair for complex type B aortic dissection with thoracoabdominal extension, 12 patients (10 men; mean age 58.7 years, range 44–76) demonstrated distal true lumen collapse and a perfused abdominal false lumen despite successful sealing of the proximal tears. As an adjunctive or staged procedure, a scaffolding stent was placed for distal extension of the previously implanted stent-graft. In each case, a Sinus aortic stent, Fortress stent, or a Z-stent system was customized with maximum 2-mm oversizing versus the original stent-graft diameter. Magnetic resonance or computed tomographic angiography was performed at discharge, at 3 months, and then annually to determine false channel thrombosis, true and false lumen dimensions, and re-entry flow. Results: Delivery was successful in all cases (100%). The compressed distal true lumen (mean 4±3 mm) was reconstructed to a mean width of 21±3 mm, and malperfusion was abolished without any obstruction of the abdominal side branches. At up to 1-year follow-up, there were no signs of expansion or distal progression of the scaffolded dissected aorta. All patients with complete thoracic thrombosis showed evidence of improved aortic remodeling; 1 patient with no false lumen thrombosis died at 11 months from thoracoabdominal aortic rupture. Conclusion: The PETTICOAT technique may offer a safe and promising adjunctive endovascular maneuver for patients with distal malapposition of the dissecting membrane and false lumen flow. The technique can both abolish distal true lumen collapse and enhance the remodeling process of the entire dissected aorta.

Safety and performance of the second-generation drug-eluting absorbable metal scaffold in patients with de-novo coronary artery lesions (BIOSOLVE-II): 6 month results of a prospective, multicentre, non-randomised, first-in-man trial

BACKGROUND Absorbable scaffolds were designed to overcome the limitations of conventional, non-absorbable metal-based drug-eluting stents. So far, only polymeric absorbable scaffolds are commercially available. We aimed to assess the safety and performance of a novel second-generation drug-eluting absorbable metal scaffold (DREAMS 2G) in patients with de-novo coronary artery lesions. METHODS We did this prospective, multicentre, non-randomised, first-in-man trial at 13 percutaneous coronary intervention centres in Belgium, Brazil, Denmark, Germany, Singapore, Spain, Switzerland, and the Netherlands. Eligible patients had stable or unstable angina or documented silent ischaemia, and a maximum of two de-novo lesions with a reference vessel diameter between 2·2 mm and 3·7 mm. Clinical follow-up was scheduled at months 1, 6, 12, 24, and 36. Patients were scheduled for angiographic follow-up at 6 months, and a subgroup of patients was scheduled for intravascular ultrasound, optical coherence tomography, and vasomotion assessment. All patients were recommended to take dual antiplatelet treatment for at least 6 months. The primary endpoint was in-segment late lumen loss at 6 months. We did analysis by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT01960504. FINDINGS Between Oct 8, 2013, and May 22, 2015, we enrolled 123 patients with 123 coronary target lesions. At 6 months, mean in-segment late lumen loss was 0·27 mm (SD 0·37), and angiographically discernable vasomotion was documented in 20 (80%) of 25 patients. Intravascular ultrasound assessments showed a preservation of the scaffold area (mean 6·24 mm(2) [SD 1·15] post-procedure vs 6·21 mm(2) [1·22] at 6 months) with a low mean neointimal area (0·08 mm(2) [0·09]), and optical coherence tomography did not detect any intraluminal mass. Target lesion failure occurred in four (3%) patients: one (<1%) patient died from cardiac death, one (<1%) patient had periprocedural myocardial infarction, and two (2%) patients needed clinically driven target lesion revascularisation. No definite or probable scaffold thrombosis was observed. INTERPRETATION Our findings show that implantation of the DREAMS 2G device in de-novo coronary lesions is feasible, with favourable safety and performance outcomes at 6 months. This novel absorbable metal scaffold could be an alternative to absorbable polymeric scaffolds for treatment of obstructive coronary disease. FUNDING Biotronik AG.

Percutaneous Endovascular Repair of Aneurysm After Previous Coarctation Surgery

Background—Formation of aortic aneurysm late after surgical repair of coarctation carries a significant risk of rupture and lethal outcome, and repeat surgery is associated with a 14% in-hospital mortality rate and morbidity from paraplegia, injury to the central nervous system, or from bleeding. The potential of nonsurgical endovascular repair by the use of stent-grafts in lieu of repeat surgery for postcoarctation aneurysm is unknown. Methods and Results—The concept of postsurgical endovascular stent-graft placement was evaluated with respect to feasibility and safety in 6 consecutive patients with late aneurysm formation after coarctation repair. All patients had aneurysm formation late after patch aortoplasty; placement of an elephant trunk during surgical repair of secondary type I dissection preceded formation of a local aneurysm in 2 cases. Patient age was 49±12 years, ranging from 31 to 68 years. Transluminal placement of customized stent-grafts was successful, with no 30-day or 1-year intervention-related mortality or morbidity. Follow-up survey of 11 to 47 months revealed optimal reconstruction of the thoracic aorta; 1 patient died 11 months after endovascular repair from cancer. Conclusions—Nonsurgical aortic reconstruction of postsurgical thoracic aneurysms forming late after coarctation repair is safe and feasible; interventional stent-graft placement has the potential to avoid repeat surgery of postsurgical aortic aneurysm.

Transcatheter transplantation of autologous skeletal myoblasts in postinfarction patients with severe left ventricular dysfunction.

Purpose: To report a case-controlled safety and feasibility study of transcatheter transplantation of autologous skeletal myoblasts as a stand-alone procedure in patients with ischemic heart failure. Methods: Six men (mean age 66.2±7.2 years) were eligible for transcatheter transplantation of autologous skeletal myoblasts cultured from quadriceps muscle biopsies. Six other men (mean age 65.7±6.3 years) were selected as matched controls (no muscle biopsies). A specially designed injection catheter was advanced through a femoral sheath into the left ventricle cavity, where myoblasts in solution (0.2 mL/injection) were injected into the myocardium via a 25-G needle. At baseline and in follow-up, both groups underwent Holter monitoring, a 6-minute walk test, New York Heart Association (NYHA) class determination, and echocardiography with dobutamine challenge. Results: Skeletal myoblast transplantation was technically successful in all 6 patients with no complications; 19±10 injections were performed per patient (210times106±150times106 cells implanted per patient). Left ventricular ejection fraction (LVEF) rose from 24.3%±6.7% at baseline to 32.2%±10.2% at 12 months after myoblast implantation (p=0.02 versus baseline and p<0.05 versus controls); in matched controls, LVEF decreased from 24.7%±4.6% to 21.0%±4.0% (p = NS). Walking distance and NYHA functional class were significantly improved at 1 year (p= 0.02 and p= 0.001 versus baseline, respectively), whereas matched controls were unchanged. Conclusions: Transcatheter transplantation of autologous skeletal myoblasts for severe left ventricular dysfunction in postinfarction patients is feasible, safe, and promising. Scrutiny with randomized, double-blinded, multicenter trials appears warranted.

Etiology, pathogenesis and management of thoracic aortic aneurysm

Given the growing proportion of elderly people in Western societies and the increasing prevalence of chronic hypertension, the management of aneurysmal aortic disease is an ever growing challenge. Although degenerative changes in the aortic wall are common to thoracic aortic aneurysm (TAA) and to various types of dissection in general, TAA can result from specific heritable disorders of connective tissues. Today, increased awareness of vascular diseases and access to tomographic imaging equipment facilitate the diagnosis of TAA, even when asymptomatic. While most TAA cases with ascending aortic involvement are treated with surgical repair (primarily valve-preserving techniques), aneurysms of the distal arch and descending thoracic aorta are amenable to alternatives to classic open repair such as the emerging endovascular treatment techniques. In this Review, we provide a comprehensive overview of the etiology, pathophysiology and clinical management of patients with TAA, and discuss the most recent literature on the condition.

Strategies for subacute/chronic type B aortic dissection: the Investigation Of Stent Grafts in Patients with type B Aortic Dissection (INSTEAD) trial 1-year outcome.

OBJECTIVE Endovascular stent grafting represents a novel concept for type B aortic dissection both in the acute and subacute/chronic setting, with an unknown effect on outcomes. METHODS In a prospective trial 140 patients with stable type B dissection were randomly subjected to elective stent-graft placement in addition to optimal medical therapy (n = 72) or to optimal medical therapy (n = 68) with surveillance (arterial pressure according to World Health Organization guidelines ≤ 120/80 mm Hg). The primary end point was 1-year all-cause mortality, whereas aorta-related mortality, progression (with need for conversion or additional endovascular or open surgical intervention), and aortic remodeling were secondary end points. RESULTS There was no difference in all-cause mortality: cumulative survival was 97.0% ± 3.4% with optimal medical therapy versus 91.3% ± 2.1% with thoracic endovascular aortic repair (P = .16). Moreover, aorta-related mortality was not different (P = .42), and the risk for the combined end point of aorta-related death (rupture) and progression (including conversion or additional endovascular or open surgical intervention) was similar (P = .86). Three neurologic adverse events occurred in the thoracic endovascular aortic repair group (1 paraplegia, 1 stroke, and 1 transient paraparesis) versus 1 episode of paraparesis with medical treatment. Finally, aortic remodeling (with true-lumen recovery and thoracic false-lumen thrombosis) occurred in 91.3% with thoracic endovascular aortic repair versus 19.4% with medical treatment (P < .001), which is suggestive of continued remodeling. CONCLUSIONS In survivors of uncomplicated type B aortic dissection, elective stent-graft placement does not improve 1-year survival and adverse events, despite favorable aortic remodeling.