Antonino G.M. Marullo

Stent thrombosis with drug-eluting and bare-metal stents: evidence from a comprehensive network meta-analysis

BACKGROUND The relative safety of drug-eluting stents and bare-metal stents, especially with respect to stent thrombosis, continues to be debated. In view of the overall low frequency of stent thrombosis, large sample sizes are needed to accurately estimate treatment differences between stents. We compared the risk of thrombosis between bare-metal and drug-eluting stents. METHODS For this network meta-analysis, randomised controlled trials comparing different drug-eluting stents or drug-eluting with bare-metal stents currently approved in the USA were identified through Medline, Embase, Cochrane databases, and proceedings of international meetings. Information about study design, inclusion and exclusion criteria, sample characteristics, and clinical outcomes was extracted. FINDINGS 49 trials including 50,844 patients randomly assigned to treatment groups were analysed. 1-year definite stent thrombosis was significantly lower with cobalt-chromium everolimus eluting stents (CoCr-EES) than with bare-metal stents (odds ratio [OR] 0·23, 95% CI 0·13-0·41). The significant difference in stent thrombosis between CoCr-EES and bare-metal stents was evident as early as 30 days (OR 0·21, 95% CI 0·11-0·42) and was also significant between 31 days and 1 year (OR 0·27, 95% CI 0·08-0·74). CoCr-EES were also associated with significantly lower rates of 1-year definite stent thrombosis compared with paclitaxel-eluting stents (OR 0·28, 95% CI 0·16-0·48), permanent polymer-based sirolimus-eluting stents (OR 0·41, 95% CI 0·24-0·70), phosphorylcholine-based zotarolimus-eluting stents (OR 0·21, 95% CI 0·10-0·44), and Resolute zotarolimus-eluting stents (OR 0·14, 95% CI 0·03-0·47). At 2-year follow-up, CoCr-EES were still associated with significantly lower rates of definite stent thrombosis than were bare-metal (OR 0·35, 95% CI 0·17-0·69) and paclitaxel-eluting stents (OR 0·34, 95% CI 0·19-0·62). No other drug-eluting stent had lower definite thrombosis rates compared with bare-metal stents at 2-year follow-up. INTERPRETATION In randomised studies completed to date, CoCr-EES has the lowest rate of stent thrombosis within 2 years of implantation. The finding that CoCr-EES also reduced stent thrombosis compared with bare-metal stents, if confirmed in future randomised trials, represents a paradigm shift. FUNDING The Cardiovascular Research Foundation.

Aortic root replacement with cryopreserved allograft for prosthetic valve endocarditis

UNLABELLED BACKGROUND Our strategy has been to treat aortic prosthetic valve endocarditis (PVE) with radical debridement of infected tissue and aortic root replacement with a cryopreserved aortic allograft. This study examines the effectiveness of this strategy on hospital mortality and morbidity, recurrent endocarditis, and survival. METHODS From 1988 through 2000, 103 patients with aortic PVE underwent root replacement with a cryopreserved aortic allograft. Abscesses were present in 78%, and aortoventricular discontinuity was present in 40%. Thirty-two patients had at least one previous operation for endocarditis. In 23 patients with a history of native valve endocarditis, the allograft was implanted after one episode (17 patients), two episodes (5 patients), or three episodes of PVE (1 patient). In the 80 patients without a history of native valve endocarditis, the allograft was placed after one previous aortic valve replacement (57 patients), two (19), or three (4) previous aortic valve replacements. Among the 92 patients with positive cultures, 52 had staphylococcal organisms, 20 had streptococcal, 6 had fungal, 4 had gram-negative, and 6 had enterococcal organisms. Mean follow-up was 4.3 +/- 2.9 years. RESULTS Hospital mortality was 3.9%. Permanent pacemakers were required in 31 patients. Survival at 1 year, 2 years, 5 years, and 10 years was 90%, 86%, 73%, and 56%, respectively, with a risk of 5.3% per year after 6 months. Four patients underwent reoperation for recurrent PVE of the allograft (95% freedom from recurrent PVE at > or = 2 years). Risk of recurrent PVE peaked at 9 months and then declined to a low level by 18 months. CONCLUSIONS A strategy of radical debridement and aortic root replacement with a cryopreserved aortic allograft for aortic PVE is safe, effective, and recommended.

Mitral valve repair with aortic valve replacement is superior to double valve replacement

OBJECTIVES Double valve replacement has been advocated for patients with combined aortic and mitral valve disease. This study investigated the alternative that, when feasible, mitral valve repair with aortic valve replacement is superior. PATIENTS AND METHODS From 1975 to 1998, 813 patients underwent aortic valve replacement with either mitral valve replacement (n = 518) or mitral valve repair (n = 295). Mitral valve disease was rheumatic in 71% and degenerative in 20%. Mitral valve replacement was more common in patients with severe mitral stenosis (P =.0009), atrial fibrillation (P =.0006), and in patients receiving a mechanical aortic prosthesis (P =.0002). These differences were used for propensity-matched multivariable comparisons. Follow-up extended reliably to 16 years, mean 6.9 +/- 5.9 years. RESULTS Hospital mortality rate was 5.4% for mitral valve repair and 7.0% for replacement (P =.4). Survivals at 5, 10, and 15 years were 79%, 63%, and 46%, respectively, after mitral valve repair versus 72%, 52%, and 34%, respectively, after replacement (P =.01). Late survival was increased by mitral valve repair rather than replacement (P =.03) in all subsets of patients, including those with severe mitral valve stenosis. After repair of nonrheumatic mitral valves, 5-, 10-, and 15-year freedom from valve replacement was 91%, 88%, and 86%, respectively; in contrast, after repair of rheumatic valves, it was 97%, 89%, and 75% at these intervals. CONCLUSIONS In patients with double valve disease, aortic valve replacement and mitral valve repair (1) are feasible in many, (2) improve late survival rates, and (3) are the preferred strategy when mitral valve repair is possible.

Bridging regenerative medicine based therapies into the 21st Century: solo or symphony?

Clinical translation in the field of regenerative medicine means manufacturing a safe, reproducible and effective clinical product for the benefit of patients. This represents the ultimate goal of applied research, but beyond researchers and clinicians, multiple intermediate players are involved, including other researchers, reviewers, funding agencies, scientific societies, guideline authors, and policy regulators. Consequently, bridging translational research and regenerative medicine therapies into the 21 st Century requires a resolute effort. We envisage that strategic and synergistic efforts in seven key areas will facilitate the mainstream adoption and implementation of regenerative medicine based therapies.

Durability of combined aortic and mitral valve repair

BACKGROUND This study was undertaken to determine the durability of combined aortic and mitral valve repair. METHODS From 1979 through 1999, 158 patients underwent simultaneous aortic and mitral valve repair. Multivariable, multi-phase hazard function analysis was used to determine risk factors for the outcomes of death and reoperation. RESULTS Hospital mortality was 3%. Survival after operation was 97%, 93%, 82%, and 62% after 30 days and 1, 5, and 10 years, respectively. Risk factors for late death included aortic stenosis (p = 0.0001), older age (p = 0.002), and abnormal left ventricular function (p = 0.007). Thirty-six patients required reoperation for valvular dysfunction, and freedom from reoperation was 94%, 82%, and 65% after 1, 5, and 10 years, respectively. Risk factors for reoperation included severe aortic regurgitation (p = 0.004), aortic cusp shaving (p = 0.05), mitral valve chordal transfer (p = 0.004), and bovine pericardial annuloplasty (p = 0.002). Five-year freedoms from endocarditis, thromboembolism, and hemorrhage were 97%, 98%, and 99%, respectively, with freedom from any of these valve-related morbidities of 99%, 95%, and 94% after 1, 5, and 10 years, respectively. CONCLUSIONS Double valve repair is associated with acceptable late survival and excellent freedom from valve-related morbidity, but limited durability. Therefore, double valve repair should be reserved for patients who cannot be anticoagulated, and should be used with caution in patients with aortic stenosis, rheumatic valve disease, or anterior mitral leaflet pathology.

Hybrid Aortic Arch Debranching With Staged Endovascular Completion in DeBakey Type I Aortic Dissection

BACKGROUND We assess midterm results of a hybrid approach to DeBakey type I aortic dissection using a new multibranched Dacron graft to create, by relocation of the inflow openings to the arch vessels toward the aortic root, a new aortic arch for an easier and safer second-staged endovascular stent grafting of the distal thoracic aorta. METHODS From March 2006 to July 2008 24 patients with DeBakey type I aortic dissection underwent ascending aorta and aortic arch replacement with debranching of epiaortic vessels using a new prosthesis to create an optimal landing zone for possible subsequent endovascular stent grafting of the distal thoracic aorta. Fifteen patients, who postoperatively presented a residual patent distal false lumen, underwent a successful second-stage endovascular stent-graft implantation. RESULTS One patient died after the surgical stage while there was no death after the endovascular stage with hospital mortality of 4.2%. Follow-up confirmed complete thrombosis of the residual distal false lumen in 95.6% and partial thrombosis in 4.4% of patients with no evidence of endoleaks in the cases that required the endovascular procedure. Overall actuarial survival at 28 months is 92.1% ± 7.9% with 100% freedom from reoperation. CONCLUSIONS Hybrid treatment of DeBakey type I aortic dissection with aortic arch debranching, using a new multibranched prosthesis (Lupiae Graft; Vascutek Terumo Inc, Scotland, United Kingdom) is confirmed to facilitate the subsequent endovascular completion. Midterm results in terms of survival and distal false lumen thrombosis are satisfactory. Further study of this operation is warranted to confirm the effectiveness and the durability of this approach.

State of the Art on the Evidence Base in Cardiac Regenerative Therapy: Overview of 41 Systematic Reviews.

Objectives. To provide a comprehensive appraisal of the evidence from secondary research on cardiac regenerative therapy. Study Design and Setting. Overview of systematic reviews of controlled clinical trials concerning stem cell administration or mobilization in patients with cardiovascular disease. Results. After a systematic database search, we short-listed 41 reviews (660 patients). Twenty-two (54%) reviews focused on acute myocardial infarction (AMI), 19 (46%) on chronic ischemic heart disease (IHD) or heart failure (HF), 29 (71%) on bone marrow-derived stem-cells (BMSC), and 36 (88%) to randomized trials only. Substantial variability among reviews was found for validity (AMSTAR score: median 9 [minimum 3]; 1st quartile 9; 3rd quartile 10; maximum 11), effect estimates (change in ejection fraction from baseline to follow-up: 3.47% [0.02%; 2.90%; 4.22%; 6.11%]), and citations (Web of Science yearly citations: 4.1 [0; 2.2; 6.5; 68.9]). No significant association was found between these three features. However, reviews focusing on BMSC therapy had higher validity scores (P = 0.008) and showed more pronounced effect estimates (P = 0.002). Higher citations were associated with journal impact factor (P = 0.007), corresponding author from North America/Europe (P = 0.022), and inclusion of nonrandomized trials (P = 0.046). Conclusions. Substantial heterogeneity is apparent among these reviews in terms of quality and effect estimates.

New insights into the steen solution properties: Breakthrough in antioxidant effects via NOX2 downregulation

Ex vivo lung perfusion (EVLP) allows perfusion and reconditioning of retrieved lungs for organ transplantation. The Steen solution is specifically designed for this procedure but the mechanism through which it elicits its activity is still to be fully clarified. We speculated that Steen solution may encompass antioxidant properties allowing a reestablishment of pulmonary tissue homeostasis. Blood samples from 10 healthy volunteers were recruited. Platelets and white cells were incubated with Steen solution or buffer solution as control and stimulated with suitable agonists. Reactive oxidant species (ROS), soluble NOX2 (sNOX2-derived peptide), a marker of NADPH oxidase activation, p47phox translocation to cell membrane and isoprostanes production, as marker of oxidative stress, and nitric oxide (NO), a powerful vasodilator and antioxidant molecule, were measured upon cell stimulation. The Steen solution significantly inhibited p47phox translocation and NOX2 activation in platelets and white cells. Consistent with this finding was the reduction of oxidative stress as documented by a significantly lowered formation of ROS and isoprostanes by both platelets and white cells. Finally, cell incubation with Steen solution resulted in enhanced generation of NO. Herewith, we provide the first evidence that Steen solution possesses antioxidant properties via downregulation of NADPH oxidase activity and enhanced production of NO.

Β-blockers treatment of cardiac surgery patients enhances isolation and improves phenotype of cardiosphere-derived cells

Β-blockers (BB) are a primary treatment for chronic heart disease (CHD), resulting in prognostic and symptomatic benefits. Cardiac cell therapy represents a promising regenerative treatment and, for autologous cell therapy, the patients clinical history may correlate with the biology of resident progenitors and the quality of the final cell product. This study aimed at uncovering correlations between clinical records of biopsy-donor CHD patients undergoing cardiac surgery and the corresponding yield and phenotype of cardiospheres (CSs) and CS-derived cells (CDCs), which are a clinically relevant population for cell therapy, containing progenitors. We describe a statistically significant association between BB therapy and improved CSs yield and CDCs phenotype. We show that BB-CDCs have a reduced fibrotic-like CD90 + subpopulation, with reduced expression of collagen-I and increased expression of cardiac genes, compared to CDCs from non-BB donors. Moreover BB-CDCs had a distinctive microRNA expression profile, consistent with reduced fibrotic features (miR-21, miR-29a/b/c downregulation), and enhanced regenerative potential (miR-1, miR-133, miR-101 upregulation) compared to non-BB. In vitro adrenergic pharmacological treatments confirmed cytoprotective and anti-fibrotic effects of β1-blocker on CDCs. This study shows anti-fibrotic and pro-commitment effects of BB treatment on endogenous cardiac reparative cells, and suggests adjuvant roles of β-blockers in cell therapy applications.

Long-term effectiveness of dual site left ventricular cardiac resynchronization therapy in a patient with congestive heart failure.

This article describes a case of cardiac resynchronization therapy (CRT) performed with dual site left ventricular pacing. The main clinical and functional long‐term results are in agreement with the most recent data regarding traditional CRT. Furthermore, this innovative pacing modality allowed optimal inter‐ and intraventricular resynchronization. (PACE 2004; 27[Pt. I]:805–807)