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Ventricular assist devices (VADs) are becoming more commonplace in the hospital and community settings as the number of patients living with heart failure increases. Patients being discharged after hospitalization for heart failure rose from 399 000 in 1979 to 1 099 000 in 2004, an increase of 175%. Patients with heart failure become severely debilitated finding activities of daily living including eating, bathing, and walking a great effort. Patients with end-stage heart failure are often sent home on inotropic therapies and referred to hospice care. The use of VADs for these patients can dramatically improve both the quality and the length of life. VADs can be broadly categorized as being either continuous flow (fluid dynamic) or pulsatile (volume displacement) and either can be used as short- or long-term support devices. The critical care nurse is in a unique position to educate patients with chronic heart failure on options available to improve their quality of life including VAD therapy. VADs are available for destination therapy for those not meeting transplant criteria, offering a longer quality of life. As centers gain more experience and referrals are made earlier in the disease process, VAD patient care will be more streamlined decreasing length of stay. [ABSTRACT FROM AUTHOR]

Mechanical heart valve prostheses are based on older designs without changes during the last 40 years. Today, there is an unmet need for less thrombogenic mechanical prostheses. Analysis of the relationship between flow characteristics and thromboembolic complications is possible using numerical and biomolecular flow studies that have shown that the reverse rather than the forward flow is responsible for local platelet activation and thrombosis. After peak flow, leaflets experience flow deceleration and the leaflets are still widely open when the flow becomes zero. The closure of the valve starts with the onset of reverse flow. Therefore, the valve closes extremely fast with most of the leaflet traveling angle occurring in <10 ms with excessively high reverse flow velocities. The pivoting spaces, so-called "Hot Spots" should be eliminated to prevent pathologic shear stress that result in thrombosis. A novel tri-leaflet valve combines favorable hemodynamics with the durability of mechanical heart valve. This valve closes within 60 ms, much slower than bi-leaflet valves and similar to the closing mode of a tissue valve. Micro-particle image velocimetry did not show critical regions of flow stagnation and zones of excessive shear in the pivoting region suggesting low potential for thrombogenic events that should allow to avoid long-term anticoagulation., Competing Interests: Declaration of Competing Interest D. Lapeyre, is the founder of Novostia and hold stocks. T. Carrel, W. Dembitsky, B. de Mol, G. Dreyfus, B. Meuris are members of the Advisory Board of Novostia. B. Meuris, D. Obrist and B. Vennemann received research funding. H. Schaff has no conflict of interest to declare., (Copyright © 2020 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Increased shear stress conferred upon the circulation by continuous-flow pumps is associated with hemocompatibility-related adverse events, principally bleeding within the gastrointestinal system, and linked to the degradation of high-molecular-weight multimers (HMWMs) of von Willebrand factor (vWF). We evaluated the structure and functional characteristics of vWF HMWMs in patients with the fully magnetically levitated centrifugal-flow HeartMate 3 (HM3) and the continuous axial-flow HeartMate II (HMII) pump. Findings were correlated with bleeding events., Methods: In a prospective, multicenter, comparative cohort study, 60 patients from the Multicenter Study of MagLev Technology in Patients Undergoing Mechanical Circulatory Support Therapy With HeartMate 3 Continued Access Protocol (NCT02892955) with an HM3 pump were compared with 30 randomly selected HMII patients from the PREVENtion of HeartMate II Pump Thrombosis study (NCT02158403) biobank. The primary end point was the difference in the normalized vWF HMWM ratio (ratio of the HMWMs to the intermediate- and low-molecular-weight multimers, normalized to pooled plasma from healthy volunteers) between the HM3 and the HMII pump at 90 days after implantation. Assay tests for vWF activity, vWF antigen, vWF activity to antigen ratio, coagulation factor VIII activity, and ADAMTS13 activity were measured by using standard protocols. Differences in these markers were compared in the context of clinical characteristics and correlated with adjudicated bleeding events within the HM3 group., Results: Of 51 and 29 evaluable patients in the HM3 and HMII arms, respectively, those implanted with the HM3 pump exhibited greater preservation of the vWF HMWM ratio than those with the HMII pump at 90 days after implantation (54.1% vs 42.4%, p < 0.0001). Laboratory values for all vWF assays (antigen, activity, and coagulation factor VIII activity) remained within the normal functional range with no significant differences observed between the pumps at 90 days after implantation. At baseline, there was a decrease in the structural integrity of vWF HMWMs that correlated with increasing heart failure severity as measured by the Interagency Registry for Mechanically Assisted Circulatory Support profile. Multivariable modeling identified the HM3 pump as the only independent variable that determined post-implantation preservation of the structural integrity of vWF HMWMs., Conclusions: This prospective, multicenter comparative analysis study demonstrates that the fully magnetically levitated centrifugal-flow HM3 left ventricular assist device is associated with greater preservation of the structure of vWF HMWMs than the HMII mechanical bearing axial-flow pump., (Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.)

Cardiomyocyte ploidy has been described but remains obscure in cardiac interstitial cells. Ploidy of c-kit+ cardiac interstitial cells was assessed using confocal, karyotypic, and flow cytometric technique. Notable differences were found between rodent (rat, mouse) c-kit+ cardiac interstitial cells possessing mononuclear tetraploid (4n) content, compared to large mammals (human, swine) with mononuclear diploid (2n) content. In-situ analysis, confirmed with fresh isolates, revealed diploid content in human c-kit+ cardiac interstitial cells and a mixture of diploid and tetraploid content in mouse. Downregulation of the p53 signaling pathway provides evidence why rodent, but not human, c-kit+ cardiac interstitial cells escape replicative senescence. Single cell transcriptional profiling reveals distinctions between diploid versus tetraploid populations in mouse c-kit+ cardiac interstitial cells, alluding to functional divergences. Collectively, these data reveal notable species-specific biological differences in c-kit+ cardiac interstitial cells, which could account for challenges in extrapolation of myocardial from preclinical studies to clinical trials., Competing Interests: Competing interestsThe authors declare no competing interests.

Senescence-associated dysfunction deleteriously affects biological activities of human c-Kit + cardiac progenitor cells (hCPCs), particularly under conditions of in vitro culture. In comparison, preservation of self-renewal and decreases in mitochondrial reactive oxygen species (ROS) are characteristics of murine CPCs in vivo that reside within hypoxic niches. Recapitulating hypoxic niche oxygen tension conditions of ∼1% O 2 in vitro for expansion of hCPCs rather than typical normoxic cell culture conditions (21% O 2 ) could provide significant improvement of functional and biological activities of hCPCs. hCPCs were isolated and expanded under permanent hypoxic (hCPC-1%) or normoxic (hCPC-21%) conditions from left ventricular tissue explants collected during left ventricular assist device implantation. hCPC-1% exhibit increased self-renewal and suppression of senescence characteristics relative to hCPC-21%. Oxidative stress contributed to higher susceptibility to apoptosis, as well as decreased mitochondrial function in hCPC-21%. Hypoxia prevented accumulation of dysfunctional mitochondria, supporting higher oxygen consumption rates and mitochondrial membrane potential. Mitochondrial ROS was an upstream mediator of senescence since treatment of hCPC-1% with mitochondrial inhibitor antimycin A recapitulated mitochondrial dysfunction and senescence observed in hCPC-21%. NAD + /NADH ratio and autophagic flux, which are key factors for mitochondrial function, were higher in hCPC-1%, but hCPC-21% were highly dependent on BNIP3/NIX-mediated mitophagy to maintain mitochondrial function. Overall, results demonstrate that supraphysiological oxygen tension during in vitro expansion initiates a downward spiral of oxidative stress, mitochondrial dysfunction, and cellular energy imbalance culminating in early proliferation arrest of hCPCs. Senescence is inhibited by preventing ROS through hypoxic culture of hCPCs. Stem Cells 2019;37:555-567., (© AlphaMed Press 2019.)

Rationale: Biological significance of c-Kit as a cardiac stem cell marker and role(s) of c-Kit+ cells in myocardial development or response to pathological injury remain unresolved because of varied and discrepant findings. Alternative experimental models are required to contextualize and reconcile discordant published observations of cardiac c-Kit myocardial biology and provide meaningful insights regarding clinical relevance of c-Kit signaling for translational cell therapy., Objective: The main objectives of this study are as follows: demonstrating c-Kit myocardial biology through combined studies of both human and murine cardiac cells; advancing understanding of c-Kit myocardial biology through creation and characterization of a novel, inducible transgenic c-Kit reporter mouse model that overcomes limitations inherent to knock-in reporter models; and providing perspective to reconcile disparate viewpoints on c-Kit biology in the myocardium., Methods and Results: In vitro studies confirm a critical role for c-Kit signaling in both cardiomyocytes and cardiac stem cells. Activation of c-Kit receptor promotes cell survival and proliferation in stem cells and cardiomyocytes of either human or murine origin. For creation of the mouse model, the cloned mouse c-Kit promoter drives Histone2B-EGFP (enhanced green fluorescent protein; H2BEGFP) expression in a doxycycline-inducible transgenic reporter line. The combination of c-Kit transgenesis coupled to H2BEGFP readout provides sensitive, specific, inducible, and persistent tracking of c-Kit promoter activation. Tagging efficiency for EGFP+/c-Kit+ cells is similar between our transgenic versus a c-Kit knock-in mouse line, but frequency of c-Kit+ cells in cardiac tissue from the knock-in model is 55% lower than that from our transgenic line. The c-Kit transgenic reporter model reveals intimate association of c-Kit expression with adult myocardial biology. Both cardiac stem cells and a subpopulation of cardiomyocytes express c-Kit in uninjured adult heart, upregulating c-Kit expression in response to pathological stress., Conclusions: c-Kit myocardial biology is more complex and varied than previously appreciated or documented, demonstrating validity in multiple points of coexisting yet heretofore seemingly irreconcilable published findings., (© 2018 American Heart Association, Inc.)

Key Points: Autologous cardiac progenitor cell (CPC) therapy is a promising approach for treatment of heart failure (HF). There is an unmet need to identify inherent deficits in aged/diseased human CPCs (hCPCs) derived from HF patients in the attempts to augment their regenerative capacity prior to use in the clinical setting. Here we report significant functional correlations between phenotypic properties of hCPCs isolated from cardiac biopsies of HF patients, clinical parameters of patients and expression of the P2Y 14 purinergic receptor (P2Y 14 R), a crucial detector for extracellular UDP-sugars released during injury/stress. P2Y 14 R is downregulated in hCPCs derived from HF patients with lower ejection fraction or diagnosed with diabetes. Augmenting P2Y 14 R expression levels in aged/diseased hCPCs antagonizes senescence and improves functional responses. This study introduces purinergic signalling modulation as a potential strategy to rejuvenate and improve phenotypic characteristics of aged/functionally compromised hCPCs prior to transplantation in HF patients., Abstract: Autologous cardiac progenitor cell therapy is a promising alternative approach to current inefficient therapies for heart failure (HF). However, ex vivo expansion and pharmacological/genetic modification of human cardiac progenitor cells (hCPCs) are necessary interventions to rejuvenate aged/diseased cells and improve their regenerative capacities. This study was designed to assess the potential of improving hCPC functional capacity by targeting the P2Y 14 purinergic receptor (P2Y 14 R), which has been previously reported to induce regenerative and anti-senescence responses in a variety of experimental models. c-Kit + hCPCs were isolated from cardiac biopsies of multiple HF patients undergoing left ventricular assist device implantation surgery. Significant correlations existed between the expression of P2Y 14 R in hCPCs and clinical parameters of HF patients. P2Y 14 R was downregulated in hCPCs derived from patients with a relatively lower ejection fraction and patients diagnosed with diabetes. hCPC lines with lower P2Y 14 R expression did not respond to P2Y 14 R agonist UDP-glucose (UDP-Glu) while hCPCs with higher P2Y 14 R expression showed enhanced proliferation in response to UDP-Glu stimulation. Mechanistically, UDP-Glu stimulation enhanced the activation of canonical growth signalling pathways ERK1/2 and AKT. Restoring P2Y 14 R expression levels in functionally compromised hCPCs via lentiviral-mediated overexpression improved proliferation, migration and survival under stress stimuli. Additionally, P2Y 14 R overexpression reversed senescence-associated morphology and reduced levels of molecular markers of senescence p16 INK4a , p53, p21 and mitochondrial reactive oxygen species. Findings from this study unveil novel biological roles of the UDP-sugar receptor P2Y 14 in hCPCs and suggest purinergic signalling modulation as a promising strategy to improve phenotypic properties of functionally impaired hCPCs., (© 2017 The Authors. The Journal of Physiology © 2017 The Physiological Society.)

Rationale: Autologous stem cell therapy using human c-Kit + cardiac progenitor cells (hCPCs) is a promising therapeutic approach for treatment of heart failure (HF). However, hCPCs derived from aged patients with HF with genetic predispositions and comorbidities of chronic diseases exhibit poor proliferative and migratory capabilities, which impair overall reparative potential for injured myocardium. Therefore, empowering functionally compromised hCPCs with proregenerative molecules ex vivo is crucial for improving the therapeutic outcome in patients with HF., Objective: To improve hCPC proliferation and migration responses that are critical for regeneration by targeting proregenerative P2Y 2 nucleotide receptor (P2Y 2 R) activated by extracellular ATP and UTP molecules released following injury/stress., Methods and Results: c-Kit + hCPCs were isolated from cardiac tissue of patients with HF undergoing left ventricular assist device implantation surgery. Correlations between P2 nucleotide receptor expression and hCPC growth kinetics revealed downregulation of select P2 receptors, including P2Y 2 R, in slow-growing hCPCs compared with fast growers. hCPC proliferation and migration significantly improved by overexpressing or stimulating P2Y 2 R. Mechanistically, P2Y 2 R-induced proliferation and migration were dependent on activation of YAP (yes-associated protein)-the downstream effector of Hippo signaling pathway., Conclusions: Proliferation and migration of functionally impaired hCPCs are enhanced by P2Y 2 R-mediated YAP activation, revealing a novel link between extracellular nucleotides released during injury/stress and Hippo signaling-a central regulator of cardiac regeneration. Functional correlations exist between hCPC phenotypic properties and P2 purinergic receptor expression. Lack of P2Y 2 R and other crucial purinergic stress detectors could compromise hCPC responsiveness to presence of extracellular stress signals. These findings set the stage for subsequent studies to assess purinergic signaling modulation as a potential strategy to improve therapeutic outcome for use of hCPCs in patients with HF., (© 2017 American Heart Association, Inc.)

Rationale: The relative actions and synergism between distinct myocardial-derived stem cell populations remain obscure. Ongoing debates on optimal cell population(s) for treatment of heart failure prompted implementation of a protocol for isolation of multiple stem cell populations from a single myocardial tissue sample to develop new insights for achieving myocardial regeneration., Objective: Establish a robust cardiac stem cell isolation and culture protocol to consistently generate 3 distinct stem cell populations from a single human heart biopsy., Methods and Results: Isolation of 3 endogenous cardiac stem cell populations was performed from human heart samples routinely discarded during implantation of a left ventricular assist device. Tissue explants were mechanically minced into 1 mm 3 pieces to minimize time exposure to collagenase digestion and preserve cell viability. Centrifugation removes large cardiomyocytes and tissue debris producing a single cell suspension that is sorted using magnetic-activated cell sorting technology. Initial sorting is based on tyrosine-protein kinase Kit (c-Kit) expression that enriches for 2 c-Kit + cell populations yielding a mixture of cardiac progenitor cells and endothelial progenitor cells. Flowthrough c-Kit - mesenchymal stem cells are positively selected by surface expression of markers CD90 and CD105. After 1 week of culture, the c-Kit + population is further enriched by selection for a CD133 + endothelial progenitor cell population. Persistence of respective cell surface markers in vitro is confirmed both by flow cytometry and immunocytochemistry., Conclusions: Three distinct cardiac cell populations with individualized phenotypic properties consistent with cardiac progenitor cells, endothelial progenitor cells, and mesenchymal stem cells can be successfully concurrently isolated and expanded from a single tissue sample derived from human heart failure patients., (© 2017 American Heart Association, Inc.)

Background: Surgical positioning of the HeartMate II (HMII) left ventricular assist device assuring an unobstructed blood flow path is essential for optimal device function and hemodynamic support. We report a non-invasive radiologic assessment of HMII position after implant and long-term follow-up., Methods: We reviewed 132 consecutive patients (age 64 ± 14 years; 86% male; 60% destination therapy) implanted with an HMII from January 2009 to December 2012 and followed for them for up to 4 years. A radiologist measured pump position, pocket depth and cannula angles using chest radiography. Changes over time were determined in 64 of these patients with pairs of radiographs immediately after implant and at an average of 2.0 ± 0.7 years of follow-up., Results: The axis of the pump relative to the spine was 92 ± 10° at baseline and 94 ± 9° at 2 years (n = 64, p = 0.02), and inflow cannula angles averaged 21 ± 13° from vertical at baseline and 20 ± 12° at 2 years (p = not statistically significant). More than 90% of angle measurements showed <15° movement over the follow-up duration. There was a small but significant superior pump migration from a depth of 12.7 ± 2.7 cm to 10.4 ± 2.6 cm (p < 0.001). There were no cannula obstructions or instances of right ventricular assist device use. The 30-day operative mortality was 3.0%. Prolonged inotrope dependence occurred in 5.3% (7 of 126) of patients, and low rates of pump thrombosis of 0.018 event/patient-year (0 at 3 months) and stroke 0.074 event/patient-year were noted., Conclusion: Non-invasive radiographic measurements of surgical pump placement designed to avoid pump and cannula malposition demonstrate stable position with minimal pump migration., (Copyright © 2015 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.)

In cardiovascular surgery, hemostatic complexities require the provision of blood products to control bleeding as well as the use of a number of hemostatic agents, some of which cause significant morbidity. Among these agents is prothrombin complex concentrates (PCC), however there is no clear consensus on PCC use in cardiovascular surgery. To investigate the safety of PCC in patients undergoing left ventricular assist device (LVAD) placement, we reviewed our single institution experience to examine the incidence of thromboembolic events and a variety of hospital markers including morbidity and mortality. A retrospective review was conducted of patients who underwent LVAD placement between January 2010 and October 2012. Patients who received intraoperative PCC constituted the PCC group (n = 41) and those who did not constituted the non-PCC group (n = 27). The overall incidence of thromboembolic events at 3 months postoperative was 12 (29.3%) in the PCC group compared with six (22.2%) in the non-PCC group, respectively (p > 0.05). Morbidity did not differ between groups and one patient in the PCC group died. The intraoperative use of PCC in LVAD insertion does not appear to be associated with a significant increase in thromboembolic events; however, larger randomized trials are needed to confirm these findings.

Despite significant improved survival with continuous flow left ventricular assist devices (LVADs), complications related to aortic valve insufficiency, gastrointestinal bleeding, stroke, pump thrombosis, and hemolysis have dampened the long term success of these pumps. Evolution has favored a pulsatile heart pump to be able to deliver the maximum flow at different levels of systemic vascular resistance, confer kinetic energy to the flow of blood past areas of stenosis and generate low shear stress on blood elements. In this perspective, we suggest that lack of pulsatility may be one factor that has limited the success of continuous flow LVADs and suggest that research needs to focus on methods to generate pulsatility either by the native heart or by various speed modulation algorithms., (Copyright © 2015 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.)

Human cardiac progenitor cells (hCPC) improve heart function after autologous transfer in heart failure patients. Regenerative potential of hCPCs is severely limited with age, requiring genetic modification to enhance therapeutic potential. A legacy of work from our laboratory with Pim1 kinase reveals effects on proliferation, survival, metabolism, and rejuvenation of hCPCs in vitro and in vivo. We demonstrate that subcellular targeting of Pim1 bolsters the distinct cardioprotective effects of this kinase in hCPCs to increase proliferation and survival, and antagonize cellular senescence. Adult hCPCs isolated from patients undergoing left ventricular assist device implantation were engineered to overexpress Pim1 throughout the cell (PimWT) or targeted to either mitochondrial (Mito-Pim1) or nuclear (Nuc-Pim1) compartments. Nuc-Pim1 enhances stem cell youthfulness associated with decreased senescence-associated β-galactosidase activity, preserved telomere length, reduced expression of p16 and p53, and up-regulation of nucleostemin relative to PimWT hCPCs. Alternately, Mito-Pim1 enhances survival by increasing expression of Bcl-2 and Bcl-XL and decreasing cell death after H2O2 treatment, thereby preserving mitochondrial integrity superior to PimWT. Mito-Pim1 increases the proliferation rate by up-regulation of cell cycle modulators Cyclin D, CDK4, and phospho-Rb. Optimal stem cell traits such as proliferation, survival, and increased youthful properties of aged hCPCs are enhanced after targeted Pim1 localization to mitochondrial or nuclear compartments. Targeted Pim1 overexpression in hCPCs allows for selection of the desired phenotypic properties to overcome patient variability and improve specific stem cell characteristics., (© 2015 by The American Society for Biochemistry and Molecular Biology, Inc.)

Proper left ventricular assist device (LVAD) insertion will help maximize LVAD flow and may reduce adverse events such as right heart failure and pump thrombosis. Although no standardized insertion technique has been universally accepted, the goals are: unobstructed inflow cannula, unobstructed outflow graft with avoidance of right ventricular compression, and prevention of pump migration. To achieve these objectives for the HeartMate II LVAD, we delineate four principles: proper pump pocket creation, optimized positioning of inflow cannula and outflow graft, proper pump position in the body, and fixation. These basic principles are easy to implement and have been beneficial in our patients, assuring long-term unobstructed LVAD flow., (© 2015 The Authors. Journal of Cardiac Surgery published by Wiley Periodicals, Inc.)

Background: Ventricular assist devices (VADs) improve survival and quality of life in patients with advanced heart failure, but their use is frequently complicated by infection. There are limited data on the microbiology and epidemiology of these infections., Methods and Results: One hundred fifty patients scheduled for VAD implantation were enrolled (2006-2008) at 11 US cardiac centers and followed prospectively until transplantation, explantation for recovery, death, or for 1 year. Eighty-six patients (57%) received HeartMate II devices. Data were collected on potential preoperative, intraoperative, and postoperative risk factors for infection. Clinical, laboratory, and microbiological data were collected for suspected infections and evaluated by an infectious diseases specialist. Thirty-three patients (22%) developed 34 VAD-related infections with an incidence rate of 0.10 per 100 person-days (95% confidence interval, 0.073-0.142). The median time to infection was 68 days. The driveline was the most commonly infected site (n=28); 18 (64%) were associated with invasive disease. Staphylococci were the most common pathogen (47%), but pseudomonas or other Gram-negative bacteria caused 32% of infections. A history of depression and elevated baseline serum creatinine were independent predictors of VAD infection (adjusted hazard ratio=2.8 [P=0.007] and 1.7 [P=0.023], respectively). The HeartMate II was not associated with a decreased risk of infection. VAD infection increased 1-year mortality (adjusted hazard ratio=5.6; P<0.0001)., Conclusions: This prospective, multicenter study demonstrates that infection frequently complicates VAD placement and is a continuing problem despite the use of newer, smaller devices. Depression and renal dysfunction may increase the risk of VAD infection. VAD infection is a serious consequence because it adversely affects patient survival., Clinical Trial Registration: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01471795.

Background: Aortic valve integrity is crucial for optimal left ventricular assist device (LVAD) support. Pre-existing native aortic insufficiency, aortic valve incompetence acquired during support, as well as previously placed prosthetic aortic valves present unique problems for these patients., Methods: We reviewed and analyzed data for 28 patients who underwent left ventricular outflow tract closure associated with HeartMate I (n =12) and HeartMate II (n = 16) LVAD insertion or exchange. Indications for valve closure, surgical technique, LVAD function, survival rates and complications were retrospectively analyzed. Survival rates were compared with those of HeartMate LVAD patients (n = 104) who did not undergo aortic valve closure., Results: Indications for closure included native aortic valve insufficiency (10 patients), aortic valve deterioration after prolonged LVAD support (8 patients) and previously placed mechanical (9 patients) or bioprosthetic aortic prostheses (1 patient). There were 2 operative and 5 late deaths (mean 227 days post-operatively). Of the deaths, none were due to aortic valve closure. Actuarial survival was 78% at 1 year and 53% at 3 years, which was statistically better than for our patients with an intact aortic outflow (61% at 1 year, 45% at 3 years; p < 0.05). Five patients had transplants, 1 patient was successfully bridged to recovery, and 15 patients remain on LVAD support. No patient with outflow closure developed regurgitation, embolization or compromised LVAD support., Conclusion: Outflow tract closure in LVAD-supported patients is safe, often necessary and well tolerated., (Copyright © 2011 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.)

The duration times of left ventricular assist system (LVAS) support have increased because of prolonged wait times for transplant and the more frequent use of devices for destination therapy. The HeartMate LVAS, the only device approved for bridge to transplant and destination therapy, has limited durability, making replacement increasingly necessary. Since 1996, we have exchanged 19 left ventricular assist devices in 15 patients (11 men: mean age, 57.1 years; range, 33-77 years). Most of the devices (14) were replaced with the HeartMate vented electric/extended-lead vented electric pump; five devices were exchanged for a HeartMate II LVAS. Bearing failure was the most frequent reason for exchange (15 of 19 pumps); four of the 19 pumps also had active device-related infections at the time of exchange. There were no early deaths (30 days). Overall survival (Kaplan-Meier) was 85% at 1 year, 67% at 2 years, and 56% at 3 years. Three patients had transplants (mean, 518 days); six patients died during support (mean, 934 days), and six patients remain on LVAS support (mean, 1,219 days). One patient has been on device for over 6 years. Left ventricular assist devices exchange is becoming increasingly likely and can be associated with acceptably low-operative mortality rates and good intermediate-term survival.

Background: The HeartMate XVE left ventricular assist device is a valuable treatment option for patients with end-stage heart failure. During the past several years, the XVE has undergone a series of design enhancements to improve reliability. We compared the reliability of the two most recent design iterations of the XVE pump (stitch modification to the inflow valve assembly and new inflow valve housing redesign) to the earlier VE version., Methods: A retrospective evaluation of device reliability was performed for 268 devices implanted in 245 patients (VE: n = 167 devices, 147 patients, implant dates October 16, 1998, to December 19, 2003; XVE: n = 101 devices, 98 patients, implant dates August 1, 2002, to April 14, 2004)., Results: Median duration of device support for the VE and XVE was 159 days (range, 0 to 1,206 days) and 229 days (range, 0 to 693 days), respectively (p = 0.495). Significantly fewer major device malfunctions occurred within the XVE group as compared with the VE group (6 versus 36, respectively; p = 0.0003). The number of major device malfunctions per patient-year of support for inflow valve dysfunction, bearing wear, and other failures for the VE and XVE were 0.2 versus 0.04 (p = 0.006), 0.16 versus 0.01 (p = 0.005), and 0.06 versus 0.04 (p = 1.000), respectively. The freedom from major device malfunction at 1 year was 76% +/- 6% for the VE and 97% +/- 2% for the XVE device (p < 0.001). The freedom from death as a result of major device malfunction at 1 year was 97% +/- 2% for the VE and 98% +/- 2% for the XVE (p = 0.698)., Conclusions: Design enhancements to the HeartMate XVE have significantly reduced the incidence of major device malfunctions compared with the earlier VE model because of a reduction in failure modes from bearing wear and inlet valve dysfunction. Further follow-up is necessary to establish the long-term durability of the most recent XVE pump version.

Congestive heart failure is an increasingly widespread debilitating fatal condition that generates a high cost to patients, society, and health care systems. Nearly 6.5 million people in Europe and 5 million people in the United States have congestive heart failure. Unlike most cardiovascular diseases in industrialized countries, congestive heart failure is becoming more common. Therapies include medical approaches, implantable assist devices, and cardiac transplantation. Mechanical assistance devices rather than medical therapy offer improvement in quality of life and survival.

Background: Patients with advanced heart failure may require long-term support with an intracorporeal left ventricular assist device (LVAD) before cardiac transplant, while awaiting myocardial recovery, or during destination therapy. Compared with the diagnosis of native heart dysfunction, there is less experience with the assessment of recurrent heart failure after LVAD placement., Methods: Ten patients (9 men, 1 woman; age, 58 +/- 11 years) were studied after LVAD placement. Six patients were studied because of recurrent heart failure; the remaining 4 had other indications for study and are reported here as controls. Cardiac catheterization, including LVAD and cannulae catheterization, and angiography were performed., Results: Inflow cannula valve regurgitation by LVAD angiography was found in 3 cases. Patients with regurgitation had a mean increased resting LVAD rate of 105 beats/min (range, 90-120); LVAD output exceeded forward cardiac output (LVAD - thermodilution cardiac output = +3.7 liters/min [0.6-6.4]). Inflow cannula obstruction identified with a filling phase pressure gradient between the left ventricle and the LVAD was found in 3 additional patients. Patients with obstruction had decreased resting LVAD rates (50 beats/min, all patients); LVAD output was less than the forward cardiac output (LVAD - thermodilution cardiac output = -2.3 liters/min [-0.8 to -3.5]). Compared with those with inflow valve regurgitation, patients with cannula obstruction had higher pulmonary capillary wedge pressures; phasic left ventricular pressure variation was reduced. Patients with cannula dysfunction underwent surgical intervention, and 4 of 6 were long-term survivors., Conclusions: When heart failure recurs after LVAD placement, abnormalities of the inflow cannula are common. Cardiac catheterization can confirm the diagnosis before surgical intervention. Hemodynamic coupling between the left ventricle and the LVAD is increased with inflow valve regurgitation and reduced with cannula obstruction.

Background: Left ventricular assist device (LVAD) failure and malfunction rates are critical gauges for establishing LVADs as a long-term therapy for end-stage heart failure patients. These device performance measures, however, have been inadequately characterized in the bridge-to-transplantation literature., Methods: REMATCH is a randomized trial that compares optimal medical management with LVAD implantation for patients with end-stage heart failure. An independent committee adjudicated patient outcomes. The primary endpoint--survival--was analyzed by intention to treat using the log-rank statistic. Frequency of event occurrence was analyzed by Poisson regression. The time to first event was analyzed by the product limit method. Device performance was disaggregated into confirmed malfunctions and system failures. The latter were events in which patients could not be rescued with backup circulatory support measures., Results: The 1-year survival rate was 52% (95% confidence limit [CL]; 40%-63%) for LVAD patients versus 28% (95% CL; 17%-39%) for medical patients and the 2-year survival rate was 29% (95% CL; 19%-40%) for LVAD patients versus 13% (95% CL; 5%-22%) for medical patients. System failure was 0.13 per patient per year and the confirmed LVAD malfunction rate was 0.90. Freedom from device replacement was 87% at 1 year and 37% at 2 years., Conclusions: Despite the observed rates of device malfunction and replacement, LVAD implantation confers clinically significant improvement with regard to survival as compared with medical management. Device modifications and innovations for infection management exhibit great promise of improving device performance in the near future.

Favorable long-term patient outcome after insertion of a left ventricular assist device (LVAD) as a bridge to recovery or destination therapy for the treatment of end-stage cardiomyopathy is adversely affected by pathophysiologic changes affecting the heart. Alterations in the native aortic valve apparatus, specifically aortic valve cusp fusion, is an example of such a phenomenon and may especially affect patients in cases of bridge to recovery, a rare but reported event. A retrospective review of the last 33 LVAD placements at our institution was conducted, including reviews of operative reports and pathologic examinations of the native hearts. Seven hearts were found to have varying degrees of aortic valve cusp fusion after chronic LVAD support (63-1, 339 days). Five of these patients had native aortic valves, and two had bioprosthetic valves. The left ventricular outflow tracts in two patients were surgically occluded at the time of LVAD insertion. Aortic valve cusp fusion occurs in roughly 25% of patients on chronic LVAD support. This phenomenon may prove to be clinically significant by creating a potential source of emboli and infection. In addition, in the case of myocardial recovery, left ventricular outflow tract obstruction could limit parallel flow and produce suprasystemic ventricular pressures that in turn would elevate left ventricular end diastolic pressures. The latter may contribute to further myocardial injury, ultimately limiting the ability of an otherwise recovered heart to be weaned from LVAD support.

This article reviews the effects of chronic left ventricular assist device implantation on functional changes in patients with end-stage heart disease. Functional recovery can be measured by using response to exercise, quality-of-life surveys, improvements in noncardiac organ function, or changes in metabolic and neurohormonal levels. Recovery in intrinsic function of the heart can be assessed by changes in cardiac pump function or in baseline histological or biochemical abnormalities. Improvements in all of these areas have been found, although many reported studies are limited by a small sample size from selected subsets of patients rather than consecutive series.

Background: Use of a permanent left ventricular assist device (LVAD) has been proposed as an alternate treatment of patients with end-stage heart failure. The purpose of this study was to compare the functional capacity of patients following implantation of a LVAD vs heart transplant (HTx)., Methods: Eighteen patients from 6 centers who received an intracorporeal LVAD as a bridge to HTx underwent treadmill testing 1 to 3 months post-LVAD and again post-HTx. Baseline and peak measurements, including oxygen consumption, blood pressures, and respiratory rate were made during each treadmill test., Results: Peak oxygen consumption was 14.5+/-3.9 ml/kg/minute post-LVAD and 17.5+/-5.0 ml/kg/minute post-HTx (p < .005). The percentage of the predicted peak oxygen consumption based on gender, weight, and age was 39.5%+/-5.5% post-LVAD and 47.7%+/-10.9% post-HTx (p < .005). Exercise duration was lower post-LVAD than post-HTx (10.3+/-4.2 minute vs 12.5+/-5.4 minute, p < .05). After LVAD implantation, peak total oxygen consumption correlated with peak LVAD rate and output. Eight patients reached an LVAD rate of 120 beats per minute (bpm) before the conclusion of exercise, the maximum rate for the outpatient electric device. The peak respiratory exchange ratio post-LVAD was 1.15+/-0.22 and post-HTx was 1.15+/-0.18, consistent with a good effort in both groups., Conclusions: Patients demonstrated a lower functional capacity post-LVAD than post-HTx. For some patients functional capacity post-LVAD may be improved by a higher maximum LVAD rate and output.

Up to 10% of patients who arrive at the hospital with acute myocardial infarction (AMI) present with or develop cardiogenic shock. Some patients, despite inotropes and intra-aortic balloon pump (IABP) placement, are not hemodynamically stable enough to undergo emergent revascularization. The use of percutaneous extracorporeal life support (ECLS) can stabilize patients to allow effective therapy. In a retrospective review of the first 100 patients emergently placed on ECLS by a nurse-supported physician insertion technique at Sharp Memorial Hospital, 10 patients underwent placement of ECLS after out-of hospital AMI. All AMI patients required intubation for respiratory failure and temporary CPR for cardiovascular collapse before initiation of ECLS. Of the 10 AMI patients placed on ECLS, four (40%) are currently long-term survivors (5.1 +/- 4.2 years; range, 6 months to 11 years). All survivors underwent successful revascularization after placement on ECLS. The cause of death in the other six patients was neurologic insufficiency in two, ineffective ECLS in two, and recurrent cardiovascular collapse after weaning from bypass in two. Total CPR time before initiation of cardiopulmonary bypass was 17 +/- 10.3 minutes for the survivors and 54.2 +/-11.1 minutes for the nonsurvivors (p < 0.001). The average time on ECLS was 29 +/- 26 hours for the survivors and 30 +/-67 hours for the nonsurvivors (p = NS). Leg complications were common among long-term survivors, associated with the use of ECLS (three ischemia, one infection). After AMI and cardiovascular collapse, insertion of ECLS may permit long-term patient survival.

Mechanical circulatory support used as a bridge to chronic transplantation is now a firmly established treatment modality. Trials evaluating circulatory assist for permanent circulatory assist device implications are underway. A population of patients is beginning to emerge who are resuscitated using readily available "acute" devices and need long-term supporting "chronic" device to bridge either cardiac transplantation or permanent device implantation. Careful management of this new acute-to-chronic bridge group will maximize the chances of a successful long-term outcome. The best strategies for management may only unfold by later analysis of larger populations. This article summarizes the current utilization of acute and chronic devices, as well as the small but growing population of acute-to-chronic bridge patients, and suggests what seem today to be sound management principles for them.

The postoperative course of the patient undergoing pulmonary thromboendarterectomy poses a unique series of challenges in terms of ventilatory care and hemodynamic management. Experience, cooperation, and interaction are necessary among the various disciplines providing care for these patients during the preoperative, operative, and postoperative phases of care. The purpose of this article is to share the approach necessary for the optimal postoperative care of the patient undergoing thromboendarterectomy, to present the theoretical justification for this care, and to delineate the areas of uncertainty that still exist.

Optimal reduction in pulmonary vascular resistance caused by chronic pulmonary embolism is obtained by bilateral pulmonary thromboendarterectomy with removal of occlusive material in all bronchopulmonary segmental arteries that are partially or completely obstructed. The most effective way to obtain this goal is the use of median sternotomy with cardiopulmonary bypass, deep hypothermia, and intermittent periods of circulatory arrest. During circulatory arrest, thromboendarterectomy is performed by specially designed dissectors that allow simultaneous dissection and removal of blood from the surgical field. The operative mortality rate for pulmonary thromboendarterectomy at the University of California, San Diego, between 1990 and 1998 was 9.2% in 1,049 patients.

The purpose of this study, was to ascertain whether delayed sternal closure (DSC) could eliminate the need for an intra-aortic balloon pump (IABP) or ventricular assist device (VAD) in patients with low cardiac output syndrome (LCOS) following coronary artery bypass grafting surgery (CABG). To investigate this, the records of 3014 patients undergoing CABG were retrospectively reviewed. Sixty (2.0%) patients had a relative or absolute contraindication to IABP or VAD use and required DSC for LCOS. DSC resolved 45 (75%) of these patients' LCOS, requiring an average of 1.6 +/- 0.7 days and producing a mean change in cardiac index of +1.0 +/- 0.3 L/min/m2. Fifteen (25%) of these patients did not resolve their LCOS after DSC and required either an IABP (11) or a VAD (4). Significant postoperative morbidity occurred in 22 (36.7%) patients but were not related to DSC. Only one (1.7%) sternal wound infection occurred from a total of 147 patient-days of DSC. Operative mortality was 47 per cent (28) but was not unexpected based on the number of urgent/emergent (48; 80%) and reoperative (40; 67%) procedures but does not appear to be related to the technique of DSC. DSC appears to be a simple and safe method for treating LCOS following CABG. It is effective in resolving the majority of patients' LCOS without the addition of any significant morbidity. DSC also spares these patients the added morbidity, mortality, and cost associated with circulatory assist devices.

Most centers consider medically unresponsive pulmonary hypertension an absolute contraindication to orthotopic cardiac transplantation because the alternative surgical therapy, heterotopic graft placement, is associated with decreased survival, although most patients normalize their pulmonary hemodynamics postoperatively. Orthotopic transplantation in patients with elevated, but responsive pulmonary pressures, also is associated with an increased operative mortality rate and decreased long-term survival. The authors present the case of a patient with medically unresponsive pulmonary hypertension who was mechanically supported in an effort to improve his orthotopic transplant candidacy and decrease his risk. After informed consent, a HeartMate left ventricular assist device (LVAD) was inserted and the pulmonary hemodynamic response was monitored. Immediately before LVAD insertion, the pulmonary artery pressure (PA) was 74/28 mmHg with a transpulmonary gradient (TPG) of 28 mmHg, and a pulmonary vascular resistance (PVR) of 6.6 Wood units, despite prolonged dobutamine, milrinone, and prostaglandin E1 infusions. After 10 weeks of LVAD support, pressure and resistance improved; pulmonary artery pressure was 28/15 mmHg, transpulmonary gradient was 15 mmHg, and pulmonary vascular resistance was 2.8 Wood units. This patient subsequently underwent an uneventful orthotopic heart transplant. At 1 year after transplantation, pulmonary artery hemodynamics were normal (PA 34/14 mmHg, TPG at 8 mmHg, and PVR at 1.5 Wood units). The authors recommend the consideration of LVAD placement in patients with medically unresponsive pulmonary artery hypertension to assess PA responsiveness and improve the patient's orthotopic cardiac transplant candidacy and decrease the operative risk. However, several weeks may be needed for normalization of pressure and resistance.

Background: Long-term implantation of a left ventricular assist device (LVAD) may be a future alternative treatment for end-stage heart failure. The objective of the present study was to determine the hemodynamic effects of supine bicycle exercise and functional capacity during upright treadmill exercise in 10 patients after LVAD implantation placed for refractory heart failure as a bridge to cardiac transplantation., Methods and Results: With supine bicycle exercise, 46 +/- 25 days after device placement, heart and LVAD rates increased in parallel from 87 +/- 12 to 117 +/- 14 bpm and 82 +/- 18 to 107 +/- 21 bpm, respectively. Peak O2 consumption was 8.2 +/- 1.7 mL O2.kg-1.min-1. Fick Systemic blood flow rose from 5.0 +/- 1.2 to 7.8 +/- 2.5 L/min. Right atrial and pulmonary capillary wedge pressures increased from 6 +/- 4 and 5 +/- 3 mm Hg to 12 +/- 5 and 13 +/- 8 mm Hg, respectively. End-diastolic left ventricular dimension increased from 3.9 +/- 1.3 to 4.8 +/- 1.6 cm; however, right ventricular dimension decreased from 3.2 +/- 1.0 to 2.3 +/- 0.9 cm. With upright treadmill exercise, peak O2 consumption was 14.1 +/- 2.9 mL O2.kg-1.min-1., Conclusions: This study indicates that exercise during long-term LVAD support is safe and is not limited by right heart decompensation. It also justifies a larger study to examine how exercise after LVAD implantation compares with that after cardiac transplantation.

Between June 1986 and October 1995, 81 patients were emergently resuscitated with a portable extracorporeal life support (ECLS) system. Venoarterial perfusion was achieved using a centrifugal pump (BioMedicus; Medtronic, Anaheim, CA) and a hollow fiber oxygenator (BARD in 56 patients; Medtronic heparin-bonded MAXIMA, [MAXIMA, Medtronic, Minneapolis, MN] in the last 25 patients. The ECLS system was used at various locations in the hospital with the setup, priming, and initiation of perfusion done by ECLS trained intensive care unit nurses. Clinical data in these patients were reviewed to analyze variables influencing survival and trends that develop as the authors' experience accumulated and the technology evolved. The indication for ECLS was cardiac arrest in 68 patients and refractory cardiogenic shock in 13 patients. Thirty-five patients (43.2%) survived > 24 hrs after termination of ECLS, whereas 20 patients (24.7%) are long-term survivors (> 30 days). The ECLS system permitted an additional therapeutic surgical intervention in 45 cases. Patients who had a surgically remediable problem were more likely to survive. Prolongation of cardiopulmonary resuscitation beyond 30 mins before initiation of ECLS correlated with a decreased likelihood of survival.

Optimal support for immediate cardiac allograft failure is unknown. With the introduction of heparin bonded extracorporeal membrane oxygenated circuits, prolonged cardiopulmonary support is possible. The authors report a case that involved 2 days of right atrial to ascending aorta extracorporeal membrane oxygenated support after immediate donor organ failure prevented the patient from exiting bypass. Continued deterioration in cardiac function led to an attempt at conversion to a total artificial heart as a bridge to retransplant. However, this procedure resulted in transbronchial exsanguination and recipient death. The autopsy showed pulmonary thrombosis with infarction and hemorrhage. The authors recommend caution in the use of extracorporeal membrane oxygenated support for patients with immediate and profound graft failure because of the increased risk of stasis thrombosis and pulmonary infarction due to sluggish pulmonary and left atrial blood flow. Instead, institution of total artificial heart or biventricular support may be preferable as the risks of thrombus and infarction are less.

A significant cost reduction is likely if patients who require coronary artery bypass grafting with significant carotid stenosis have simultaneous carotid endarterectomy and bypass grafting, provided risk is not increased. To investigate this issue, we retrospectively identified cases from February 1977 to May 1994 with first-time isolated carotid endarterectomy, coronary bypass, or combined procedures. In the isolated carotid endarterectomy population, median age was 69 years and 58% (85/146) were male, as compared with 68 years and 68% (68/100) male in the combined group; median age of the coronary bypass cohort was 65 years and 76% (381/500) male. A significantly higher percentage of patients in the coronary bypass versus combined group were in New York Heart Association functional class IV. In the combined group there was a significantly higher incidence of older age, diabetes, hypertension, hyperlipidemia, renal failure, and congestive heart failure. There was no difference among the three groups with respect to hospital mortality (0%, 3.4%, and 4.0%, respectively) and permanent stroke (0.7%, 1.2%, and 0%, respectively). Hospital costs were $4,896, $10,959 and $11,089, respectively, with a savings of $4,766 (30%), and Medicare hospital reimbursement was $8,575, $23,071, and $23,071, respectively, with a savings of $10,077 (25.3%). Thus, in appropriate patients, a combined procedure is cost effective, eliminating a second surgical procedure and the cost of the postoperative stay (3.7 +/- 2.4 days) associated with isolated carotid endarterectomy. Risk of permanent stroke or death is not increased.

Background: Myocardial hypothermia of less than 10 degrees C is an essential component of preservation of donor hearts before implantation. Here we report temperature changes and comparison of methods for maintenance of myocardial hypothermia during implantation., Methods: Twenty patients were prospectively randomized into two equal groups. In one cohort myocardial hypothermia was maintained by the "Stanford method" of continuous lavage of the pericardium and left atrium with refrigerated saline solution. In the other a cooling jacket was used without saline lavage. Temperatures at multiple sites were measured at 30-second intervals from initiation of cardiac suturing until aortic cross-clamp removal. Comparisons were made between groups at each temperature site., Results: The cooling jacket group temperatures were significantly lower at the left ventricular epicardium and endocardium than those of the Stanford method group., Conclusions: During cardiac implantation maintenance of myocardial hypothermia with a cooling jacket resulted in significantly deeper and more consistent hypothermia of the left ventricle than pericardial and left atrial lavage with refrigerated saline solution. Blood loss from aspirated saline lavage and perfusate dilution by the saline solution were eliminated.

A new technique using the Thompson self-retaining retractor system (Thompson Surgical Instruments, Inc, Traverse City, MI) to harvest lesser saphenous veins is presented. This modification, used in 10 patients undergoing redo myocardial revascularization, provided a rapid, comfortable, and convenient method for harvesting lesser saphenous veins.

Cardiopulmonary support (CPS) can resuscitate a patient with circulatory collapse during high-risk interventional procedures, although vascular complications may accompany its use. We report a patient with cardiogenic shock secondary to myocardial infarction who required extended CPS support associated with acute infarct-related coronary artery angioplasty and stent placement. Leg ischemia due to an occlusive cannula was resolved using a percutaneous anterograde perfusion device. In general, such devices may have application in patients dependent on mechanical support associated with limb ischemia.

Currently used left ventricular assist devices allow chronic mechanical cardiac support in the patient with end-stage heart failure. Recognition and treatment of problems uniquely associated with this device may be increasingly important for the invasive cardiologist as application of this technology becomes more prevalent.

The prophylactic use of aprotinin has recently been reported to be associated with a significant decrease in blood loss in patients undergoing cardiopulmonary bypass procedures. One of the primary effects of aprotinin is prevention of plasmin degradation of platelet function. Because aprotinin is commercially unavailable in the United States at this time, we evaluated epsilon-aminocaproic acid with respect to decreased perioperative blood loss. We prospectively randomized 40 patients undergoing first-time coronary artery bypass grafting without prior sternotomy into two groups: one group (n = 21) received prophylactic and preincision epsilon-aminocaproic acid and the other (n = 19) received a placebo. No significant differences existed between patient groups with respect to age, body surface area, cardiopulmonary bypass time, and aortic crossclamp time. Cumulative blood loss at 4, 8, 12, and 24 hours after chest closure was significantly less in the epsilon-aminocaproic acid group (426 +/- 242 ml versus 634 +/- 224 ml, p = 0.002, at 12 hours). Only one patient receiving epsilon-aminocaproic acid was given blood or blood components compared to five patients in the placebo group (p < 0.02). D-dimers and fibrin split products were significantly less prevalent in the epsilon-aminocaproic acid group (at 4 hours: 0/20 versus 7/16, p < 0.002 and 5/20 versus 12/19, p < 0.05, respectively). None of the patients had a perioperative myocardial infarction or cerebrovascular accident. The prophylactic administration of epsilon-aminocaproic acid results in a significant decrease in blood loss in patients undergoing first-time coronary artery bypass grafting, and blood transfusion requirements are significantly less. It may be important to administer epsilon-aminocaproic acid before skin incision to be optimally effective.

Studies of patients supported with a left ventricular assist device have considered determinants of acute survival emphasizing the role of right heart function. In patients with refractory heart failure awaiting heart transplantation, chronic left ventricular assist device implantation may provide an opportunity for rehabilitation before surgery if hemodynamics are adequate at rest and during activities of daily life. For the assessment of the efficacy of the left ventricular assist device in this setting, four patients in whom the HeartMate pneumatic left ventricular assist device had been implanted were tested during graded supine bicycle exercise with Doppler echocardiography interrogation and central hemodynamic measurements. Patients with left ventricular assist device increased total left ventricular-left ventricular assist device complex output with exercise as Fick cardiac output increased from 5.7 +/- 1.5 to 8.6 +/- 3.1 L/min (mean +/- standard deviation). In two patients, peak left ventricular assist device rate and output were either present at the start of exercise or reached at mid-exercise and were associated with abrupt increases in left ventricular filling pressures (pulmonary capillary wedge pressure = 9 to 27 mm Hg and 12 to 24 mm Hg, respectively). During exercise, left ventricular end-diastolic size and pressure increased as right ventricular dimensions decreased or remained the same (patients 1, 3, and 4: 1.7 to 1.8 cm, 4.7 to 3.9 cm, and 2.6 to 1.8 cm, respectively) despite increased right atrial filling pressures, implying a decrease in functional right ventricular diastolic compliance. Although the left ventricular assist device functioned as a series pump at rest, Fick cardiac output exceeded left ventricular assist device output during exercise consistent with parallel ejection of the left ventricle through the native aortic valve. During exercise, residual left ventricular function may contribute to the hemodynamic response by (1) active filling of the left ventricular assist device to reduce filling time and to overcome left ventricular assist device inflow cannula impedance, (2) augmentation of total cardiac output with parallel ejection out of the native aortic valve, or (3) reduction of ventricular interaction-related changes in functional right ventricular diastolic compliance. When residual left ventricular function is sufficient, hemodynamics with exercise may be limited by peak left ventricular assist device rate. Although right ventricular function may affect acute postoperative survival, residual left ventricular function and peak left ventricular assist device rate may be important determinants of exercise performance during chronic implantation. A preliminary model of factors affecting the "left ventricular-left ventricular assist device complex" performance at rest and during exercise is presented.

Venovenous extracorporeal membrane oxygenation and carbon dioxide removal was utilized to support a patient with traumatic bronchial disruption and associated injuries. With use of surface-heparinized perfusion equipment, low levels of anticoagulation were maintained allowing surgical repair of the bronchial injury and recovery from acute respiratory failure without significant hemorrhage.

Objectives: The goal of this study was to assess patients with end-stage heart disease after implantation of a left ventricular assist device at rest and during exercise compatible with activities of daily life., Background: Mechanical circulatory assistance with a left ventricular assist device is an accepted therapy for bridging patients with end-stage heart disease to heart transplantation and has been proposed for long-term implantation., Methods: Three patients (aged 37, 42 and 57 years) with end-stage heart failure required implantation of a pneumatically driven, asynchronous Thermedics left ventricular assist device while awaiting heart transplantation. All were assessed 1 month later during graded supine bicycle exercise (maximal work load 100 to 150 W). Detailed central hemodynamics, including continuous pulmonary artery oxygen saturation and oxygen consumption measurements, were obtained. Two of the patients also underwent upright treadmill exercise with oxygen consumption measurements., Results: During supine bicycle exercise, the heart rate increased from 93 +/- 37 beats/min (95% confidence interval: mean +/- t0.025 x SE) at rest to 119 +/- 54 beats/min and left ventricular assist device rate increased from 82 +/- 47 to 109 +/- 55 beats/min. Oxygen consumption increased from 3.0 +/- 0.9 to 8.7 +/- 2.9 ml oxygen/min per kg body weight. Cardiac output increased from 6.0 +/- 4.4 to 9.6 +/- 7.1 liters/min, yielding an average exercise factor of 8.5 +/- 7.7 and an exercise index of 0.83 +/- 0.61. The patients assessed during treadmill exercise achieved a maximal oxygen consumption of 14.3 and 16.7 ml of oxygen/min per kg. No thromboembolic or other complications attributable to left ventricular assist device implantation occurred during the duration of support. All patients survived orthotopic heart transplantation and are doing well., Conclusions: Significant work loads compatible with activities of daily life and adequate exercise hemodynamics were demonstrated by these patients while awaiting heart transplantation. Definitive conclusions regarding the use of this device must be viewed as preliminary because only three patients were involved in this study and the failure rate may be as high as 71% (95% confidence interval of left ventricular assist device success as a bridge to transplantation 29.3% to 100%). Final conclusions regarding the safety and efficacy of the left ventricular assist device as a possible long-term circulatory support device must await results of larger multicenter trials in progress.

Manual cardiopulmonary resuscitation is currently the standard treatment for cardiac arrest patients both in and out of the hospital. Accumulated experimental and anecdotal clinical evidence suggests enhanced survival in patients with extreme circulatory decompensation who have been emergently supported with portable cardiopulmonary bypass. Long-term survival is possible even when application is delayed, but early institution of support after cardiac arrest in selected patients offers the best survival advantages. In our hospital this has been achieved by training a team of in-house personnel to emergently prepare, apply, and temporarily manage cardiopulmonary bypass until personnel with greater specialty training arrive. Machinery needed to perform emergency cardiopulmonary bypass is currently available in all hospitals with open heart surgery programs. Simple support is often therapeutic but can also serve as a bridge to definitive diagnostic and other therapeutic procedures. Commercial units are becoming more biocompatible and easier to use, making both wider application and more prolonged support likely in the future.

Total circulatory support for acute reversible myocardial failure is rarely used in clinical situations outside the postoperative period following cardiac surgery. We treated an 8-year-old girl who suffered acute viral myocarditis and sustained cardiac arrest requiring cardiopulmonary bypass for resuscitation. This was accomplished with the use of the portable cardiopulmonary support system (CPS), which consists of a centrifugal pump and a membrane oxygenator. This patient was placed on CPS in Hawaii and transported after 3 days to San Diego (4200 km) for further mechanical support and possible heart transplantation. Adequate cardiac function returned and CPS was stopped after 6 days. She is alive and well, attending school two and a half years after the event. Prolonged use of CPS for acute myocardial failure outside the operating room, including long distance transportation, is effective and easily accomplished with currently and widely available equipment, and should be used in acute, reversible catastrophic heart disease.

Mechanically assisted recovery from shock and long-term survival of nontransplant patients with acute noncoronary myocardial decompensation have not been previously reported. We treated nine patients (aged 8 to 53 years) who were referred with acute nonischemic cardiogenic shock (pulmonary capillary wedge greater than 20, cardiac index less than 1.5 L/min/m2, mean blood pressure less than 60 mm Hg, ejection fraction less than 0.3%). Eight patients had viral prodromes, and one patient was peripartum. All patients' lungs were mechanically ventilated, and pharmacologic support failed in all patients. Two patients received steroids. All received mechanical circulatory support. Seven were initially supported with intraaortic balloon counterpulsation pumps. Two patients recovered with intraaortic balloon counterpulsation pumps alone (3 days and 4 days). Four patients received left ventricular assist devices (3, 7, 10, and 79 days), and two received biventricular support devices (10 days and 14 days). One patient was supported with extracorporeal femoral vein-to-femoral artery bypass for 6 days. Four patients required dialysis (4 days to 5 weeks). Seven patients underwent myocardial biopsies, of which three demonstrated acute myocarditis. All patients recovered ventricular function (ejection fraction greater than 0.55%), and all are New York Heart Association functional class I, 7 months to 4 1/2 years after support. Mechanical circulatory assist devices may be lifesaving for patients with acute nonischemic myocardial decompensation. Patients should be supported for at least 2 weeks before transplantation is considered.