Research Spotlight

Posted June 15th 2016

Use of a pressure wire to evaluate right heart pressures in a pre-liver transplant recipient through a peripheral iv.

James F. Trotter M.D.

James F. Trotter M.D.

Schussler, J. M., S. K. Asrani, M. A. Ramsay and J. F. Trotter (2016). “Use of a pressure wire to evaluate right heart pressures in a pre-liver transplant recipient through a peripheral iv.” Liver Transpl 22(5): 695-697.

Full text of this article.

TO THE EDITOR: The pre–liver transplant cardiovascular evaluation of recipients routinely includes echocardiography to evaluate for the presence of pulmonary hypertension (pHTN), as patients with moderate or severe pHTN have significantly increased perioperative morbidity and mortality. A recent article by Khaderi et al.(1) suggested that portopulmonary hypertension carries even longer-term risks in post–liver transplant patients. It has become standard for patients in whom screening echocardiography suggests systolic pulmonary artery (PA) pressures >45 mm Hg to undergo confirmatory invasive testing with right heart catheterization (RHC). This allows for both confirmation of these findings, as well as initiation of treatment (where appropriate) for pHTN, and subsequent successful transplantation.(2,3) The direct assessment of a patient’s pulmonary pressures requires invasive instrumentation. In a large series of patients with pHTN, the overall risk of complication is approximately 1.1%, mostly due to the access site and bleeding risk.(4) In the general population, the presence of elevated international normalized ratio (INR) or thrombocytopenia increases the risk of invasive cardiac procedures and is a relative contraindication to heart catheterization. In end-stage liver disease patients, there are few data looking at the magnitude of the increased risk. Although there is a general assumption that this risk may be mitigated by administration of blood products (such as fresh frozen plasma or platelets), vitamin K, or recombinant factor VIIa, there are no data to support these maneuvers.(5) RHC has traditionally been performed using catheters up to 8 Fr in size, placed percutaneously through the internal jugular or common femoral vein. Smaller catheters, compatible with sheaths down to 5 Fr in size, make the potential for bleeding less, but there is always the possibility that bleeding complications (sometimes due to inadvertent arterial punctures) can occur when making a venous puncture. We describe the use of a novel pressure wire to easily and safely evaluate a patient’s pulmonary pressures without the need for additional venous punctures or blood products.


Posted June 15th 2016

Effectiveness and Safety of the Impella 5.0 as a Bridge to Cardiac Transplantation or Durable Left Ventricular Assist Device.

Brian Lima M.D.

Brian Lima M.D.

Lima, B., P. Kale, G. V. Gonzalez-Stawinski, J. J. Kuiper, S. Carey and S. A. Hall (2016). “Effectiveness and safety of the impella 5.0 as a bridge to cardiac transplantation or durable left ventricular assist device.” Am J Cardiol 117(10): 1622-1628.

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Many patients with end-stage heart failure require mechanical circulatory support as a temporizing measure to enable multidisciplinary assessment for the most suitable therapeutic strategy. Impella 5.0 can be used as a bridge to decision to evaluate patients for potential recovery or bridge to next therapy (bridge to heart transplantation [BTHT] or bridge to durable left ventricular assist device or VAD [BLVAD]. Our goal was to examine single-center outcomes with the Impella 5.0 device as a bridge to next therapy (BTHT or BTLVAD). Forty patients underwent Impella 5.0 support from December 2009 to December 2015 with the intent of BTHT (n = 20) or BTLVAD (n = 20). The primary end point was survival to next therapy. Secondary end points included hemodynamic assessments and in-hospital/30-day complications. All patients were inotrope-dependent, with severely depressed left ventricular ejection fraction (12%) and renal insufficiency (creatinine 2.0 mg/dl). Most were Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) 2 (66%) with biventricular failure (65%). Thirty patients (75%) survived to next therapy, including transplant (n = 13), durable LVAD (n = 15), and recovery of native heart function (n = 2). No strokes or major bleeding events requiring surgery were observed. Acute renal dysfunction, bleeding requiring transfusion, hemolysis, device malfunction, limb ischemia occurred in 13 (33%), 11 (28%), 3 (8%), 4 (10%), and 1 (3%) patients, respectively. Survival rate to discharge and/or 30 days was 68% (27 of 40). Temporary support with the Impella 5.0 allows for an effective bridge to decision strategy for hemodynamic stabilization and multidisciplinary heart team assessment of critically ill patients with heart failure. In conclusion, many of these patients can be subsequently bridged to the next therapy with favorable outcomes.


Posted June 15th 2016

Just because you get on a scale doesn’t mean you lose weight: is Meetbaar Beter really measurably better?

Michael J. Mack M.D.

Michael J. Mack M.D.

Mack, M. and H. Baumgarten (2016). “Just because you get on a scale doesn’t mean you lose weight: Is meetbaar beter really measurably better?” Eur J Cardiothorac Surg 49(6): 1669-1670.

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The article by van Veghel et al. [1] describes a national initiative in the Netherlands termed ‘Meetbaar Beter’ or in English ‘Measurably Better’. The stated goal of this multicentre effort according to its website ‘aims to improve quality and transparency of care for patients with heart diseases by measuring limited patient-relevant outcome measures’. Those outcomes include survival, degree of health/recovery, time to recovery and return to normal activity, disutility of the care of treatment process, sustainability of health/recovery and nature of recurrences and long-term consequences of the therapy. By doing this, they are proposing to implement a ‘Value Based Healthcare Theory’ by ‘measuring patient relevant outcomes and sharing and adopting each others best practices’.


Posted June 15th 2016

Surgical versus percutaneous femoral access for delivery of large-bore cardiovascular devices (from the partner trial).

Michael J. Mack M.D.

Michael J. Mack M.D.

McCabe, J. M., P. H. Huang, D. J. Cohen, E. H. Blackstone, F. G. Welt, M. J. Davidson, T. Kaneko, M. H. Eng, K. B. Allen, K. Xu, A. M. Lowry, Y. Lei, J. Rajeswaran, D. L. Brown, M. J. Mack, J. G. Webb, C. R. Smith, M. B. Leon and A. C. Eisenhauer (2016). “Surgical versus percutaneous femoral access for delivery of large-bore cardiovascular devices (from the partner trial).” Am J Cardiol 117(10): 1643-1650.

Full text of this article.

It is unclear if surgical exposure confers a risk advantage compared with a percutaneous approach for patients undergoing endovascular procedures requiring large-bore femoral artery access. From the randomized controlled Placement of Aortic Transcatheter Valve trials A and B and the continued access registries, a total of 1,416 patients received transfemoral transcatheter aortic valve replacement, of which 857 underwent surgical, and 559 underwent percutaneous access. Thirty-day rates of major vascular complications and quality of life scores were assessed. Propensity matching was used to adjust for unmeasured confounders. Overall, there were 116 major vascular complications (8.2%). Complication rates decreased dramatically during the study period. In unadjusted analysis, major vascular complications were significantly less common in the percutaneous access group (35 [6.3%] vs 81 [9.5%] p = 0.032). However, among 292 propensity-matched pairs, there was no difference in major vascular complications (22 [7.5%] vs 28 [9.6%], p = 0.37). Percutaneous access was associated with fewer total in-hospital vascular complications (46 [16%] vs 66 [23%], p = 0.036), shorter median procedural duration (97 interquartile range [IQR 68 to 166] vs 121 [IQR 78 to 194] minutes, p <0.0001), and median length of stay (4 [IQR 2 to 8] vs 6 [IQR 3 to 10] days, p <0.0001). There were no significant differences in quality of life scores at 30 days. Surgical access for large-bore femoral access does not appear to confer any advantages over percutaneous access and may be associated with more minor vascular complications.


Posted June 15th 2016

Molecular basis for globotriaosylceramide regulation and enzyme uptake in immortalized aortic endothelial cells from Fabry mice.

Raphael Schiffmann M.D.

Raphael Schiffmann M.D.

Meng, X. L., T. S. Day, N. McNeill, P. Ashcraft, T. Frischmuth, S. H. Cheng, Z. P. Liu, J. S. Shen and R. Schiffmann (2016). “Molecular basis for globotriaosylceramide regulation and enzyme uptake in immortalized aortic endothelial cells from fabry mice.” J Inherit Metab Dis 39(3): 447-455.

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Fabry disease is caused by deficient activity of alpha-galactosidase A and subsequent intracellular accumulation of glycosphingolipids, mainly globotriaosylceramide (Gb3). Vascular endothelial cells may play important roles in disease pathogenesis, and are one of the main target cell types in therapeutic interventions. In this study, we generated immortalized aortic endothelial cell lines from a mouse model of Fabry disease. These cells retained endothelial cell-specific markers and functions. Gb3 expression level in one of these clones (referred to as FMEC2) was highly susceptible to culture media, and appeared to be regulated by glucosylceramide synthase. Results also showed that Gb3 could be upregulated by hydrocortisone. FMEC2 express the mannose 6-phosphate receptor and sortilin but not the mannose receptor. Uptake studies suggested that sortilin plays a role in the binding and internalization of mammalian cell-produced alpha-galactosidase A. Moss-aGal (a plant-made enzyme) was endocytosed by FMEC2 via a receptor other than the aforementioned receptors. In conclusion, this study suggests that glucosylceramide synthase and hydrocortisone may play important roles in modulating Gb3 levels in Fabry mouse aortic endothelial cells, and that endocytosis of recombinant alpha-galactosidase A involves a combination of multiple receptors depending on the properties of the enzyme.