William E Cohn

Baylor College of Medicine, Houston, Texas, United States

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Publications (130)345.74 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: Background The potential for myocardial reconditioning and device explantation after long-term continuous-flow LVAD support presents an opportunity to delay or avoid transplantation in select patients. Methods Thirty patients (of 811) with end-stage heart failure supported with continuous-flow LVADs were assessed for device explantation. Each patient underwent an individualized process of weaning focused on principles of ventricular unloading, gradual reconditioning, and transition to medical therapy. Results After varying reconditioning periods, 27 patients underwent LVAD explant (16 men, 11 women; age, 39±12 years). Three patients were evaluated for explantation but could not be weaned (2 men, 1 woman; age 22±6 years). The duration of LVAD support was 533±424 days (42–1937) for the explant cohort and 1097±424 days (643–1483) for the non-explant cohort. Left ventricular end diastolic dimension, LV ejection fraction, systolic pulmonary artery pressure, cardiac output, and cardiac index in the explant cohort were significantly improved at explantation (all, p<0.05). Two late deaths occurred after LVAD explantation despite satisfactory native cardiac function, and 1 patient required resumption of LVAD support 2.7 years after device removal. The remaining explant patients remain in NYHA classes I-II with medical management alone (mean survival post-explant, 1172±948 days). All 3 candidates who could not be weaned were ultimately transplanted. Conclusions The potential for recovery of native left ventricular function after long-term continouous-flow LVAD support should encourage a more aggressive approach to ventricular reconditioning with the goal of device explantation and a return to medical management, particularly in young patients with dilated cardiomyopathy.
    The Journal of Heart and Lung Transplantation 09/2014; · 5.61 Impact Factor
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    ABSTRACT: Objective Although the development of continuous flow ventricular assist devices (CF-VAD) has improved VAD reliability, VAD exchange is still occasionally necessary. The focus of this study was to analyze our institution’s entire experience with primary CF-VAD implants, evaluate baseline variables, determine which factors predict the need for exchange, and evaluate the impact of exchange on survival and event-free survival. Methods We retrospectively reviewed the data of all patients in a single center who received a primary CF-VAD implant between December 1999 and December 2013. All CF-VAD exchanges were reviewed; demographics, indications, pre-operative and operative data, and clinical outcomes were summarized. Univariate and multivariable regression analyses were performed to ascertain predictors for exchange. Time-to-event and survival analyses were also performed. Results We identified 469 patients who underwent 546 CF-VAD implantations. Of these patients, 66 (14%) underwent 77 exchanges from one CF-VAD to another. The primary indications included hemolysis or thrombosis (n=49; 63,6%), infection (n=9; 11.7%), or other causes (n=19; 24.7%). Survival was not significantly different between exchange and non-exchange groups. Multivariable regression analysis identified a history of cerebrovascular events as a significant predictor for exchange. Among exchange patients, 11 underwent heart transplantation, 3 had their CF-VADs explanted, 26 had ongoing support, and 26 died during device support. Conclusions In our series of contemporary CF-VAD exchanges, history of prior cerebrovascular events was a significant predictor for exchange. Exchange did not impact early or late survival. Our data suggest aggressive surgical treatment of pump-related complications with exchange is safe and justified.
    Journal of Thoracic and Cardiovascular Surgery 09/2014; · 3.99 Impact Factor
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    ABSTRACT: Rotary blood pumps are emerging as a viable technology for total artificial hearts, and the development of physiological control algorithms is accelerated with new evaluation environments. In this article, we present a novel hybrid mock circulation loop (HMCL) designed specifically for evaluation of rotary total artificial hearts (rTAH). The rTAH is operated in the physical domain while all vasculature elements are embedded in the numerical domain, thus combining the strengths of both approaches: fast and easy exchange of the vasculature model together with improved controllability of the pump. Parameters, such as vascular resistance, compliance, and blood volume, can be varied dynamically in silico during operation. A hydraulic–numeric interface creates a real-time feedback loop between the physical and numerical domains. The HMCL uses computer-controlled resistance valves as actuators, thereby reducing the size and number of hydraulic elements. Experimental results demonstrate a stable interaction over a wide operational range and a high degree of flexibility. Therefore, we demonstrate that the newly created design environment can play an integral part in the hydraulic design, control development, and durability testing of rTAHs.
    Artificial Organs 09/2014; 38(9). · 1.87 Impact Factor
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    ABSTRACT: A mock circulatory loop was constructed to facilitate total artificial heart development. The loop includes many novel features such as a pressure-regulated tank to simulate exercise conditions, controllable systemic and pulmonary vascular resistance to create left-right flow imbalances as seen in postural change and breathing, and a left atrial suction valve. Dual HeartMate II pumps and the BiVACOR® rotary total artificial heart were used to generate pressure and flow data characterizing the flow loop.
    08/2014; 2014:5667-70.
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    ABSTRACT: Although there is limited consensus about the strict requirement to deliver pulsatile perfusion to the human circulatory system, speed modulation of rotary blood pumps is an approach that may capture the benefits of both positive displacement and continuous flow blood pumps. In the current stage of development of the BiVACOR Total Artificial Heart emphasis is placed on providing pulsatile outflow from the pump. Multiple pulsatile speed profiles have been applied in preliminary in-vivo operation in order to assess the capability of the TAH to recreate a physiologic pulse. This paper provides an overview about recent research towards pulsatile BiVACOR operation with special emphasis on motor and control requirements and developments.
    08/2014; 2014:5659-62.
  • The Journal of Heart and Lung Transplantation 04/2014; 33(4):S204. · 5.61 Impact Factor
  • Hari R Mallidi, Jatin Anand, William E Cohn
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    ABSTRACT: Mechanical circulatory support of the failing heart has become an important means of treating end-stage heart disease. This rapidly growing therapeutic field has produced impressive clinical outcomes and has great potential to help thousands of otherwise terminal patients worldwide. In this review, we examine the state of the art of mechanical circulatory support: current practice, totally implantable systems of the future, evolving biventricular support mechanisms, the potential for myocardial recovery and adjunctive treatment methods, and miniaturized devices with expanded indications for therapy.
    Texas Heart Institute journal / from the Texas Heart Institute of St. Luke's Episcopal Hospital, Texas Children's Hospital 04/2014; 41(2):115-20. · 0.67 Impact Factor
  • The Journal of Heart and Lung Transplantation 04/2014; 33(4):S237-S238. · 5.61 Impact Factor
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    ABSTRACT: We sought to determine the outcomes for patients with advanced hepatic dysfunction undergoing HeartMate II left ventricular assist device (LVAD) implantation. Between November 1, 2003 and December 1, 2012, we implanted the HeartMate II continuous-flow LVAD in 338 patients, either for bridging to heart transplantation or for destination therapy. Twenty-three of these patients (19 men and 4 women; mean age, 47 ± 16 years) had advanced hepatic dysfunction, as characterized by alanine aminotransferase (ALT) or aspartate transaminase (AST) levels five times normal; serum total bilirubin levels three times normal; and/or necessity for a liver biopsy before or during device implantation. Of this group, 17 patients received the LVAD as a bridge to transplantation, and six patients received it for destination therapy. Nine of the 23 patients required either a transjugular or a core liver biopsy during LVAD implantation. Three patients died within the first postoperative month; the 20 surviving patients had significant improvements in their hepatic parameters. The ALT decreased from 238 ± 296 to 27 ± 13 U/L (p = 0.022), AST decreased from 209 ± 199 to 29 ± 8 U/L (p = 0.009), and total bilirubin level decreased from 6.9 ± 6.0 to 0.6 ± 0.1 mg/dL (p = 0.044). The serum albumin level increased from 3.2 ± 0.6 to 4.3 ± 0.3 g/dL (p = 0.003), and creatinine clearance increased from 77.6 ± 35.2 to 110.2 ± 35.7 mL/min/1.73 m(2) (p = 0.101). Continuous-flow LVAD support may significantly improve hepatic function, allowing patients with poor preimplant liver function to become better candidates for heart transplantation.
    Journal of Cardiac Surgery 03/2014; · 1.35 Impact Factor
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    ABSTRACT: Gelatin impregnated non-porous sealed grafts were introduced in the inflow and outflow conduits for use with the HeartMate II (HMII) to eliminate pre-clotting procedures and to reduce operative bleeding.We compared results of 67 patients who received first time LVADs with sealed inflow and outflow grafts (S-graft group) to a preceding 65 patients who received an LVAD with non-sealed grafts (NS-graft group).Overall, the amount of blood product transfusions was less in the S-graft group than in the NS-graft group (red blood cells, 4.9 ± 4.5 vs. 8.0 ± 9.4 units, P=0.022; fresh frozen plasma, 5.0 ± 3.0 vs. 8.7 ± 9.3 units, P=0.004; platelets, 2.9 ± 1.1 vs. 4.5 ± 3.5 units, P=0.001; and cryoprecipitate, 1.2 ± 0.9 vs. 2.01 ± 1.9 units, P=0.002). Within a follow-up period of 6 months, no device-related infections or strokes occurred in the S-group, but the NS-group had 1 (1.5%) driveline infections and 4 (6%) strokes. The 30-day survival rate was not significantly different between groups (P=0.053), but favored the S-group (97%) over the NS-group (88%). Use of a HMII with a sealed graft on the inflow and outflow conduits is associated with less postoperative bleeding, and may have helped to decrease the frequency of postoperative adverse events.
    ASAIO journal (American Society for Artificial Internal Organs: 1992) 03/2014; · 1.39 Impact Factor
  • Journal of Surgical Research 02/2014; 186(2):493. · 2.12 Impact Factor
  • Journal of Surgical Research 02/2014; 186(2):493. · 2.12 Impact Factor
  • William E Cohn, Hari R Mallidi, O H Frazier
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    ABSTRACT: As left ventricular assist devices (LVADs) have become more widely used for treating patients with advanced heart failure, the incidence of pump dysfunction requiring pump replacement has increased. When dysfunction is due to pump failure or driveline injury, isolated pump replacement can be curative. We have developed a quick, safe pump-exchange technique that avoids a redo sternotomy and cardiopulmonary bypass. We have used this technique to exchange malfunctioning HeartMate II LVADs in 14 consecutive patients. The patients were extubated within 3 to 6 hours, and blood loss and transfusion requirements were nominal. There were no periprocedural deaths or strokes.
    The Annals of thoracic surgery 12/2013; 96(6):2259-61. · 3.45 Impact Factor
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    ABSTRACT: Over the last 8 years, we have developed and evaluated a continuous-flow total artificial heart (CFTAH) comprising two rotary blood pumps. To understand the physiologic effects of nonpulsatile circulation, we evaluated the CFTAH in 65 calves for 90 days or less. We describe our experience with 29 calves that survived for 7 days or more. The calves received dual axial-flow (n = 24) or centrifugal-flow (n = 5) pumps. Several iterations of customized atrial cuffs were developed to facilitate an adequate anatomical fit. Pressures (arterial pressure [AoP], pulmonary artery pressure [PAP], left atrial pressure [LAP], and right atrial pressure [RAP]) and pump parameters were continuously monitored. Hematologic and biochemistry values were analyzed. After each case, a necropsy was performed. The calves survived for 7-92 days (mean, 24 days). Pressures were 94 ± 14 (AoP), 25 ± 8 (PAP), 14 ± 6 (RAP), and 16 ± 6 (LAP) mm Hg. Pump flow was maintained at 9.1 ± 1.7 L/minute (right) and 9.4 ± 1.9 L/minute (left). Hematologic and biochemistry values remained acceptable. Eight animals underwent treadmill evaluations, in which oxygen consumption (VO2) was comparable with physiologic total-body VO2. In the two animals that survived to 90 days, the end-organs appeared unremarkable at autopsy, and the CFTAH circuits were free of thrombus. Our results show that a CFTAH can maintain a large animal physiologically and hemodynamically for up to 90 days with continuous flow.
    ASAIO journal (American Society for Artificial Internal Organs: 1992) 11/2013; · 1.39 Impact Factor
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    ABSTRACT: We evaluated the effects of steady state flow and perfusion on end-organ function in a long-term calf model. The animal received a continuous-flow total artificial heart (CFTAH) that we created from two axial-flow ventricular assist devices. Pump flow, blood pressure, and other pump parameters were monitored throughout the study, as were arterial blood gas and hematologic values, including neurohormone levels. Some hematologic values were mildly abnormal transiently after surgery but returned to acceptable levels within the first week. During the 90-day study, the calf showed no signs of hemolysis or thrombosis. Its mental function remained normal, as evidenced by the animal's interest in its surroundings and response to stimuli. End-organ and vasomotor function was not adversely affected by 90 days of steady state flow. This was the first study in which CFTAH support of an animal model was maintained for this duration.
    ASAIO journal (American Society for Artificial Internal Organs: 1992) 11/2013; · 1.39 Impact Factor
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    ABSTRACT: Amiodarone is widely used worldwide as an important drug for managing supraventricular arrhythmias, regardless of its association with potentially severe side effects due to systemic toxicity. Amiodarone reduces the incidence of atrial fibrillation after cardiac surgery, but oral therapy requires a presurgery loading period, lasting from 1 to 4 weeks. In this study, we showed that it is possible to rapidly obtain therapeutic cardiac tissue levels of the drug by infusing aqueous amiodarone intrapericardially, without appreciable systemic exposure. We also examined the long-term histologic safety of intrapericardial infusion. In this observational study, 9 adult sheep, randomized into 3 groups of 3 animals each, were given low (2.5 -mg/h), medium (10-mg/h), or high (50-mg/h) dosages of amiodarone by continuous infusion intrapericardially for 72 hours. An intrapericardial drain prevented tamponade from fluid build-up. Levels of amiodarone and its active metabolite, desethylamiodarone (DEA), were assessed both in plasma and in transmural biopsy specimens taken from the left atrial appendage and left and right ventricular myocardium. Cardiac, hepatic, and renal functions were also assessed. Humane euthanization was performed after 3 months, and cardiac and thoracic tissues were assessed for evidence of epicarditis, severe fibrotic changes, or other adverse effects potentially caused by the local amiodarone administration. Pericardial infusion resulted in rapid uptake and high concentrations of amiodarone and DEA in the myocardial tissues, without an appreciable systemic presence of either drug. The highest and lowest levels of these agents were observed in the left atrium and left ventricle, respectively. Drug concentrations in all cardiac biopsy specimens were similar to, or higher than, those reportedly observed in patients taking long-term oral amiodarone. At 90 days, postmortem microscopic, biochemical, and hematologic evaluation of end-organ tissues from the 8 surviving sheep showed no adverse effects. Excessive inflammation or fibrotic changes were not observed in these 8 sheep. The ninth sheep died prematurely, and its death was deemed not to be related to this study. Short-term intrapericardial delivery of amiodarone is a safe method for rapidly obtaining therapeutic atrial-tissue drug levels. When begun perioperatively, this method may prevent postoperative atrial fibrillation similarly to oral or intravenous amiodarone therapy. However, we have shown that pericardial administration avoids systemic drug distribution and thus may greatly decrease the systemic complicationsresulting from this drug.
    Heart Surgery Forum 10/2013; 16(5):E279-86. · 0.56 Impact Factor
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    ABSTRACT: Trauma-related failure of a continuous-flow left ventricular assist device (LVAD) has not previously been reported. We present 4 cases in which LVAD complications were likely caused by external trauma and led to failure of a HeartMate II device. In 1 case, the onset of symptoms was delayed and the patient did not seek medical attention until months after the traumatic event. All 4 patients required surgical intervention, and 1 patient died of respiratory complications several months postoperatively. In conclusion, a history of external trauma should be considered as a possible etiologic factor when LVAD-supported patients in previously stable condition present with device malfunction.
    The American journal of cardiology 08/2013; · 3.58 Impact Factor
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    ABSTRACT: Successful anatomic fitting of a total artificial heart (TAH) is vital to achieve optimal pump hemodynamics after device implantation. Although many anatomic fitting studies have been completed in humans prior to clinical trials, few reports exist that detail the experience in animals for in vivo device evaluation. Optimal hemodynamics are crucial throughout the in vivo phase to direct design iterations and ultimately validate device performance prior to pivotal human trials. In vivo evaluation in a sheep model allows a realistically sized representation of a smaller patient, for which smaller third-generation TAHs have the potential to treat. Our study aimed to assess the anatomic fit of a single device rotary TAH in sheep prior to animal trials and to use the data to develop a three-dimensional, computer-aided design (CAD)-operated anatomic fitting tool for future TAH development. Following excision of the native ventricles above the atrio-ventricular groove, a prototype TAH was inserted within the chest cavity of six sheep (28-40 kg). Adjustable rods representing inlet and outlet conduits were oriented toward the center of each atrial chamber and the great vessels, with conduit lengths and angles recorded for future analysis. A three-dimensional, CAD-operated anatomic fitting tool was then developed, based on the results of this study, and used to determine the inflow and outflow conduit orientation of the TAH. The mean diameters of the sheep left atrium, right atrium, aorta, and pulmonary artery were 39, 33, 12, and 11 mm, respectively. The center-to-center distance and outer-edge-to-outer-edge distance between the atria, found to be 39 ± 9 mm and 72 ± 17 mm in this study, were identified as the most critical geometries for successful TAH connection. This geometric constraint restricts the maximum separation allowable between left and right inlet ports of a TAH to ensure successful alignment within the available atrial circumference.
    Artificial Organs 03/2013; · 1.87 Impact Factor
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    ABSTRACT: We assessed and compared the performance levels of a fiber-coupled fluorescence affinity sensor (FAS) for glucose detection in the intradermal tissue and intravascular bed during glucose clamping and insulin administration in a large animal model. Research Design and The FAS (BioTex Inc., Houston, TX) was implanted in interstitial tissue and in the intravenous space in nondiabetic, anesthetized pigs over 6-7 h. For intradermal assessment, a needle-type FAS was implanted in the upper back using a hypodermic needle. For intravenous assessment, the FAS was inserted through a catheter into the femoral artery and vein. Blood glucose changes were induced by infusion of dextrose and insulin through a catheterized ear or jugular vein. Based on retrospective analysis, the mean absolute relative error (MARE) of the sensor in blood and interstitial tissue was 11.9% [standard deviation (SD) = ±9.6%] and 23.8% (SD = ±19.4%), respectively. When excluding data sets from sensors that were affected by exogenous insulin, the MARE for those sensors tested in interstitial tissue was reduced to 16.3% (SD = ±12.5%). The study demonstrated that the performance level of the FAS device implanted in interstitial tissue and blood can be very high. However, under certain circumstances, exogenous insulin caused the glucose concentration in interstitial tissue to be lower than in blood, which resulted in an overall lower level of accuracy of the FAS device. How significant this physiological effect is in insulin-treated persons with diabetes remains to be seen. In contrast, the level of accuracy of the FAS device in blood was very high because of high mass transfer conditions in blood. While the use of the FAS in both body sites will need further validation, its application in critically ill patients looks particularly promising.
    Journal of diabetes science and technology 01/2013; 7(1):35-44.
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    ABSTRACT: Currently, long-term mechanical circulatory support (MCS) is limited to large, complex devices that require invasive, high-risk surgical implantation. These devices are mainly used in patients with late stage heart failure (HF). We are developing a novel percutaneous intra-aortic micro-axial fluid entrainment pump intended for long-term MCS in patients with earlier stage HF. This study examined the pump's hemodynamic effects in a porcine model of acute HF. In three porcine experiments, the pump was deployed in the thoracic aorta by standard cardiac catheterization techniques and was anchored with self-expanding struts. Acute cardiac dysfunction was induced by infusing esmolol continuously. Pump support increased cardiac output (+10.4%), stroke volume (+8.9%), and ejection fraction (+10.8%) while decreasing cardiac stroke work (-10.8%) and afterload (-22.7%). Furthermore, pump support significantly enhanced renal perfusion through sustained increases in both renal artery flow (+36.4%) and pressure (+73.6%). In a porcine model of acute HF, the catheter-based intra-aortic fluid entrainment pump improved hemodynamics and renal perfusion. These results suggest that the pump could improve HF outcomes and patients' quality of life by resting the heart, promoting reverse remodeling, and augmenting end-organ perfusion. Furthermore, the enhanced renal perfusion may help disrupt the cardiorenal syndrome cycle and improve HF treatment.
    ASAIO journal (American Society for Artificial Internal Organs: 1992) 01/2013; 59(3):240-5. · 1.39 Impact Factor

Publication Stats

1k Citations
345.74 Total Impact Points

Institutions

  • 2007–2014
    • Baylor College of Medicine
      • Department of Surgery
      Houston, Texas, United States
  • 2004–2014
    • Texas Heart Institute
      • Division of Cardiovascular Surgery
      Houston, Texas, United States
  • 2012
    • Vanderbilt University
      • Center for Cognitive Medicine
      Nashville, MI, United States
  • 2011
    • Texas A&M University
      College Station, Texas, United States
  • 2008–2011
    • Houston Methodist Hospital
      Houston, Texas, United States
    • University of Cincinnati
      Cincinnati, Ohio, United States
  • 2010
    • Alpert Medical School - Brown University
      • Department of Surgery
      Providence, RI, United States
  • 2009
    • St. Luke School of Medicine
      Houston, Texas, United States
  • 2006–2007
    • Université de Montréal
      • Department of Pharmacology
      Montréal, Quebec, Canada
  • 1997–2003
    • Harvard Medical School
      Boston, Massachusetts, United States
  • 1995–2002
    • Beth Israel Deaconess Medical Center
      • Department of Surgery
      Boston, Massachusetts, United States
  • 2000
    • Rhode Island Hospital
      Providence, Rhode Island, United States