Early Experience with the HeartMate Percutaneous Heart Pump from the SHIELD II Trial.

The HeartMate Percutaneous Heart Pump (PHP) is a novel circulatory support catheter delivering a self-expanding 24 French impeller across the aortic valve. The SHIELD II trial compares outcomes among heart failure patients undergoing high-risk percutaneous coronary intervention (HR-PCI) with the PHP versus Impella systems. The trial was halted in 2017 due to device malfunctions. We aimed to describe procedural, hemodynamic, and clinical outcomes among HR-PCI patients treated with PHP as part of the SHIELD II trial roll-in phase. Procedural, hemodynamic, and 90 day outcomes were assessed among patients undergoing HR-PCI with a left ventricular ejection fraction ≤35% and last patent coronary conduit, unprotected left main disease, or significant three vessel disease. The primary endpoint was the 90 day composite of cardiovascular death, myocardial infarction, stroke, repeat revascularization, major bleeding, new/worsening aortic regurgitation, and severe hypotension. Among 75 roll-in phase patients, PHP support duration was 101 ± 53 minutes with 2.5 ± 1.4 coronary lesions treated per patient. Compared with predevice values, the PHP system increased cardiac power and mean arterial pressure. Maximum recorded device flows were 0.4-6.2 L/minute with 26% (n = 19/73) and 9.6% (n = 7/73) of patients achieving peak flows above 3.5 or 5.0 L/minute, respectively. Five PHP device malfunction events (6.7%) were observed. At 90 days, the composite endpoint occurred in 24.3% (18/74) of patients. Early PHP experience demonstrated successful device performance in the majority of enrolled patients; however, unexpected malfunctions led to device revision. Completion of the SHIELD II trial will be required to confirm the safety and efficacy of this iteration of the PHP system in HR-PCI.

Comparison of everolimus-eluting bioresorbable vascular scaffolds and metallic stents: three-year clinical outcomes from the ABSORB China randomised trial.

AIMS: Absorb bioresorbable vascular scaffolds (BVS) and XIENCE cobalt-chromium everolimus-eluting stents (CoCr-EES) had comparable angiographic and clinical outcomes up to one year in patients enrolled in the ABSORB China randomised trial. Whether these favourable results with BVS continue beyond one year up to three years is unknown. In this study we sought to analyse the outcomes from the trial up to three-year follow-up. METHODS AND RESULTS: ABSORB China was a prospective, open-label, multicentre trial in which 480 patients with one or two native coronary artery lesions were randomised 1:1 to BVS (N=241) vs. CoCr-EES (N=239). Clinical endpoints included target lesion failure (TLF; cardiac death, target vessel-related myocardial infarction or ischaemia-driven target lesion revascularisation), its components, and definite/probable stent/scaffold thrombosis (ST). There were no significant differences in clinical outcomes in patients treated with BVS and CoCr-EES up to three years, including TLF (5.5% vs. 4.7%, p=0.68) and definite/probable ST (0.9% vs. 0.0%, p=0.50). STs in the BVS arm consisted of one probable subacute event at 15 days and one definite very late event at 622 days. Among 32 BVS patients with a reference vessel diameter between 2.25 and 3.75 mm by quantitative coronary angiography and in whom post-dilatation was performed at >16 atm with a balloon:scaffold diameter >1:1 and balloon ≤scaffold diameter 0.5 mm, no TLF or ST events occurred within three years. CONCLUSIONS: In the ABSORB China trial, BVS and CoCr-EES had similar results up to three-year follow-up, the time at which the scaffold has completely resorbed. BVS outcomes may be further optimised by appropriate lesion selection and implantation technique.

Bioresorbable Vascular Scaffolds Versus Metallic Stents in Patients With Coronary Artery Disease: ABSORB China Trial.

BACKGROUND: The everolimus-eluting bioresorbable vascular scaffold (BVS) is designed to achieve results comparable to metallic drug-eluting stents at 1 year, with improved long-term outcomes. Whether the 1-year clinical and angiographic results of BVS are noninferior to current-generation drug-eluting stents has not been established. OBJECTIVES: This study sought to evaluate the angiographic efficacy and clinical safety and effectiveness of BVS in a randomized trial designed to enable approval of the BVS in China. METHODS: Eligible patients with 1 or 2 de novo native coronary artery lesions were randomized to BVS or cobalt-chromium everolimus-eluting stents (CoCr-EES) in a 1:1 ratio stratified by diabetes and the number of lesions treated. Angiographic and clinical follow-up were planned at 1 year in all patients. The primary endpoint was angiographic in-segment late loss (LL), powered for noninferiority with a margin of 0.15 mm. RESULTS: A total of 480 patients were randomized (241 BVS vs. 239 CoCr-EES) at 24 sites. Acute clinical device success (98.0% vs. 99.6%; p = 0.22) and procedural success (97.0% and 98.3%; p = 0.37) were comparable in BVS- and CoCr-EES-treated patients, respectively. The primary endpoint of in-segment LL at 1 year was 0.19 ± 0.38 mm for BVS versus 0.13 ± 0.38 mm for CoCr-EES; the 1-sided 97.5% upper confidence limit of the difference was 0.14 mm, achieving noninferiority of BVS compared with CoCr-EES (pnoninferiority = 0.01). BVS and CoCr-EES also had similar 1-year rates of target lesion failure (cardiac death, target vessel myocardial infarction, or ischemia-driven target lesion revascularization; 3.4% vs. 4.2%, respectively; p = 0.62) and definite/probable scaffold/stent thrombosis (0.4% vs. 0.0%, respectively; p = 1.00). CONCLUSIONS: In the present multicenter randomized trial, BVS was noninferior to CoCr-EES for the primary endpoint of in-segment LL at 1 year. (A Clinical Evaluation of Absorb Bioresorbable Vascular Scaffold [Absorb BVS] System in Chinese Population-ABSORB CHINA Randomized Controlled Trial [RCT]; NCT01923740).

Procedural effectiveness of a novel 1.20 mm diameter angioplasty catheter: clinical and angiographic outcomes.

OBJECTIVE: To evaluate clinical and angiographic outcomes using a 1.20 mm diameter angioplasty catheter as part of a predilation strategy for coronary lesion treatment. BACKGROUND: Development of an angioplasty catheter with low crossing profile and small balloon diameter represents an opportunity to facilitate percutaneous revascularization of complex coronary disease. METHODS: Clinical and angiographic outcomes were evaluated following a predilation treatment strategy using a low profile, 1.20 mm angioplasty catheter. The primary end-point of procedural success was defined as successful device delivery, performance and lesion treatment without occurrence of perforation, flow-limiting dissection, reduction in baseline TIMI grade, or clinically significant arrhythmias, and with final achievement of TIMI 3 flow. In-hospital major adverse events were also determined. RESULTS: Among 71 patients (83 lesions), angiographic characteristics included: de novo lesion, 75.9%; saphenous vein graft 9.6%; lesion length (mean ± standard deviation), 12.27 ± 5.96 mm; reference vessel diameter, 2.61 ± 0.57 mm; lesion classification B2/C, 59.0%; baseline TIMI 0/1 flow, 4.8%. Procedural success was achieved for 98.5% (66/67) of patients. Catheter delivery to the target lesion was achieved in all patients, and the rate of device success with luminal improvement after predilation was 96.2% (75/78). No acute procedural complications were observed, and in-hospital target lesion failure occurred in 6 patients (8.5%) related to peri-procedural non-Q wave myocardial infarction. CONCLUSIONS: Coronary lesion predilation with a low profile, 1.20 mm angioplasty catheter is associated with favorable procedural safety and efficacy and may represent an effective treatment for complex coronary anatomy.

Early postmyocardial infarction survival in Murphy Roths Large mice is mediated by attenuated apoptosis and inflammation but depends on genetic background.

The Murphy Roths Large (MRL) mouse, a strain capable of regenerating right ventricular myocardium, has a high postmyocardial infarction (post-MI) survival rate compared with C57BL/6J (C57) mice. The biological processes responsible for this survival advantage are unknown. To assess the effect of genetic background, the LG/J strain, which harbours 75% of the MRL composite genome, was included in the study. The MRL survival advantage versus C57 mice (92 versus 68%, P < 0.05) occurred primarily in the first 5 days; LG/J survival was intermediate (P = n.s.). Microarray data analysis revealed an attenuation of apoptotic (P < 0.05) and stress response transcripts in MRL hearts compared with C57 hearts post-MI. Supporting the microarray results, there were fewer TUNEL-positive cells 1 day post-MI in MRL infarcts compared with C57 infarcts (P = 0.001) and fewer CD45-positive cells in the MRL infarct border zone 2 days post-MI (P < 0.01); the LG/J results were intermediate (P = n.s.). The MRL hearts had smaller infarct scars and attenuated ventricular dilatation 30 days post-MI compared with C57 hearts (P < 0.05). We conclude that the early post-MI survival advantage of MRL mice over the C57 strain is mediated at least in part by reductions in apoptosis and inflammatory infiltration, and that these reductions may influence chronic remodelling. The intermediate survival, apoptosis and inflammation profile of LG/J mice suggests that this high tolerance for MI in the MRL mouse could be derived from its shared genetic background with the LG/J mouse.

Fresh and cryopreserved, uncultured adipose tissue-derived stem and regenerative cells ameliorate ischemia-reperfusion-induced acute kidney injury.

BACKGROUND: Acute kidney injury (AKI) represents a major clinical problem with high mortality and limited causal treatments. The use of cell therapy has been suggested as a potential modality to improve the course and outcome of AKI. METHODS: We investigated the possible renoprotection of freshly isolated, uncultured adipose tissue-derived stem and regenerative cells (ADRCs) before and after cryopreservation in a rat ischemia-reperfusion (I-R) model of AKI. RESULTS: We demonstrated that ADRC therapy drastically reduced mortality (survival 100% vs. 57%, ADRC vs. controls, respectively) and significantly reduced serum creatinine (sCr on Day 3: 3.03 ± 1.58 vs. 7.37 ± 2.32 mg/dL, ADRC vs. controls, respectively). Histological analysis further validated a significantly reduced intratubular cast formation, ameliorated acute tubular epithelial cell necrosis and mitigated macrophage infiltration. Furthermore, a reduced RNA expression of CXCL2 and IL-6 was found in the ADRC group which could explain the reduced macrophage recruitment. Use of cryopreserved ADRCs resulted in an equally high survival (90% vs. 33% in the control group) and similarly improved renal function (sCr on Day 3: 4.64 ± 2.43 vs. 7.24 ± 1.40 mg/dL in controls). CONCLUSIONS: Collectively, these results suggest a potential clinical role for ADRC therapy in patients with AKI. Importantly, cryopreservation of ADRCs could offer an autologous treatment strategy for patients who are at high risk for AKI during planned interventions.

Supplementation of fat grafts with adipose-derived regenerative cells improves long-term graft retention.

Current practice of autologous fat transfer for soft tissue augmentation is limited by poor long-term graft retention. Adipose-derived regenerative cells (ADRCs) contain several types of stem and regenerative cells, which may help improve graft retention through multiple mechanisms. Using a murine fat transplantation model, ADRCs were added to transplanted fat to test whether ADRCs could improve the long-term retention of the grafts. This study showed, at both 6 and 9 months after transplantation, ADRCs not only increased graft retention by 2-fold but also improved the quality of the grafts. ADRC-supplemented grafts had a higher capillary density, indicating ADRCs could promote neovascularization. Further cell tracking and gene expression studies suggest ADRCs may promote angiogenesis and adipocyte differentiation and prevent apoptosis through the expression of various growth factors, including VEGFA and IGF-1. Taken together, these results suggest a potential clinical utility of ADRCs in facilitating autologous fat transfer for soft tissue augmentation.

Serine proteases and cardiac function.

The serine proteases of the trypsin superfamily are versatile enzymes involved in a variety of biological processes. In the cardiovascular system, the importance of these enzymes in blood coagulation, platelet activation, fibrinolysis, and thrombosis has been well established. Recent studies have shown that trypin-like serine proteases are also important in maintaining cardiac function and contribute to heart-related disease processes. In this review, we describe the biological function of corin, tissue kallikrein, chymase and urokinase and discuss their roles in cardiovascular diseases such as hypertension, cardiac hypertrophy, heart failure, and aneurysm.

Genetic modifiers of cardiac arrhythmias.

Rhythmic contraction of a four-chambered mammalian heart is a highly coordinated process, requiring a functional conduction system. Both acquired and inherited forms of arrhythmia can be life threatening, and are major causes of mortality and morbidity in developed nations. Knowledge derived from human genetics and from studies of mouse genetic models has led to the discovery of multiple molecular defects responsible for arrhythmogenesis, including mutations in ion channels, cytoplasmic ion-channel-interacting proteins, gap-junction proteins, transcription factors and, most recently, a kinase subunit. However, phenotypic expression of a given mutation does not always appear to be uniform in human patients, implying a contribution from environmental factors and/or the presence of other genetic modifiers. Accumulating evidence suggests that 'multiple hits' affecting the interaction and integrity of multiple pathways might be responsible for many forms of arrhythmia.