A comparison of surgical pulmonary embolectomy and catheter-directed lysis for life-threatening pulmonary emboli.

OBJECTIVES: Patients with life-threatening pulmonary emboli (PE) have traditionally been treated with anticoagulation alone, yet emerging data suggest that more aggressive therapy may improve short-term outcomes. The purpose of this study was to compare postoperative outcomes between catheter-directed thrombolysis (CDL) and surgical pulmonary embolectomy (SPE) in the treatment of life-threatening PE. METHODS: A retrospective single-centre observational study was conducted for patients who underwent SPE or CDL at a single US academic centre. Preprocedural and postprocedural echocardiographic data were collected. Unadjusted regression models were constructed to assess the significance of the between-group postoperative differences. RESULTS: A total of 126 patients suffered a life-threatening PE during the study period [60 SPE (47.6%), 66 CDL 52.4%]. Ten (24.4%) SPE patients and 10 (15.2%) CDL patients had massive PEs marked by preprocedural hypotension. Six (10.0%) SPE patients and 4 (6.0%) CDL patients suffered a preprocedure cardiac arrest (P = 0.41). In-hospital mortality rate was 3.3% (2) for SPE, and 3.0% (2) for CDL (P = 0.99). SPE patients were more likely to require prolonged ventilation (15.0% vs 1.5%, P = 0.01). No significant differences were found in other major complications. At baseline echocardiography, 76.9% of SPE patients and 56.9% of CDL patients had moderate or severe right ventricular (RV) dysfunction. Both treatment groups showed marked and durable improvement in echocardiographic markers of RV function from baseline at midterm follow-up. CONCLUSIONS: Both SPE and CDL can be applied to well-selected high-risk patients with low rates of morbidity and mortality. Further research is necessary to delineate which patients would benefit most from either SPE or CDL following a life-threatening PE.

Evaluation of Multiple Biological Therapies for Ischemic Cardiac Disease.

The development of cell- and gene-based strategies for regenerative medicine offers a therapeutic option for the repair and potential regeneration of damaged cardiac tissue post-myocardial infarction (MI). Human umbilical cord subepithelial cell-derived stem cells (hUC-SECs), human bone marrow-derived mesenchymal stem cells (hBM-MSCs), and human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs), all derived from human tissue, have been shown to have in vitro and in vivo therapeutic potential. Additionally, S100a1, VEGF165, and stromal-derived factor-1α (SDF-1α) genes all have the potential to improve cardiac function and/or effect adverse remodeling. In this study, we compared the therapeutic potential of hBM-MSCs, hUC-SECs, and hiPSC-CMs along with plasmid-based genes to evaluate the in vivo potential of intramyocardially injected biologics to enhance cardiac function in a mouse MI model. Human cells derived from various tissue types were expanded under hypoxic conditions and injected intramyocardially into mice that had undergone left anterior descending (LAD) artery ligation. Similarly, plasmids were also injected into three groups of mice after LAD ligation. Seven experimental groups were studied in total: (1) control (saline), (2) hBM-MSCs, (3) hiPSC-CMs, (4) hUC-SECs, (5) S100a1 plasmid, (6) VEGF165 plasmid, and (7) SDF-1α plasmid. We evaluated echocardiography, hemodynamic catheterization measurements, and histology at 4 and 12 weeks post-biologic injection. Significant improvement was observed in cardiac function and contractility in hiPSC-CM and S100a1 groups and a significant reduction in left ventricle scar within the hUC-SEC group and a slight improvement in the SDF-1α and VEGF165 groups compared to the control group. These results demonstrate the potential for new biologic therapies to reduce scar burden and improve contractile function.

REVIVE Trial: Retrograde Delivery of Autologous Bone Marrow in Patients With Heart Failure.

UNLABELLED: Cell therapy is an evolving option for patients with end-stage heart failure and ongoing symptoms despite optimal medical therapy. Our goal was to evaluate retrograde bone marrow cell delivery in patients with either ischemic heart failure (IHF) or nonischemic heart failure (NIHF). This was a prospective randomized, multicenter, open-label study of the safety and feasibility of bone marrow aspirate concentrate (BMAC) infused retrograde into the coronary sinus. Sixty patients were stratified by IHF and NIHF and randomized to receive either BMAC infusion or control (standard heart failure care) in a 4:1 ratio. Accordingly, 24 subjects were randomized to the ischemic BMAC group and 6 to the ischemic control group. Similarly, 24 subjects were randomized to the nonischemic BMAC group and 6 to the nonischemic control group. All 60 patients were successfully enrolled in the study. The treatment groups received BMAC infusion without complications. The left ventricular ejection fraction in the patients receiving BMAC demonstrated significant improvement compared with baseline, from 25.1% at screening to 31.1% at 12 months (p=.007) in the NIHF group and from 26.3% to 31.1% in the IHF group (p=.035). The end-systolic diameter decreased significantly in the nonischemic BMAC group from 55.6 to 50.9 mm (p=.020). Retrograde BMAC delivery is safe. All patients receiving BMAC experienced improvements in left ventricular ejection fraction, but only those with NIHF showed improvements in left ventricular end-systolic diameter and B-type natriuretic peptide. These results provide the basis for a larger clinical trial in HF patients. SIGNIFICANCE: This work is the first prospective randomized clinical trial using high-dose cell therapy delivered via a retrograde coronary sinus infusion in patients with heart failure. This was a multinational, multicenter study, and it is novel, translatable, and scalable. On the basis of this trial and the safety of retrograde coronary sinus infusion, there are three other trials under way using this route of delivery.

Stem cell therapy for heart failure.

"During the past decade, studies in animals and humans have suggested that cell therapy has positive effects for the treatment of heart failure. This clinical effect may be mediated by angiogenesis and reduction in fibrosis rather than by regeneration of myocytes. Increased microvasculature and decreased scar also likely lead to improved cardiac function in the failing heart. The effects of cell therapy are not limited to one type of cell or delivery technique. Well-designed, large-scale, randomized clinical trials with objective end points will help to fully realize the therapeutic potential of cell-based therapy for treating heart failure."