Zain Khalpey - Academia.edu (original) (raw)

Papers by Zain Khalpey

Transplantation, 2010

Objectives-Mixed hematopoietic chimerism is associated with islet allograft tolerance and may rev... more Objectives-Mixed hematopoietic chimerism is associated with islet allograft tolerance and may reverse autoimmunity. We developed low intensity regimens for the induction of mixed chimerism and examined effects on autoimmunity in pre-diabetic NOD mice.

Perfusion, Jan 20, 2015

Despite the clinical success and growth in the utilization of continuous flow ventricular assist ... more Despite the clinical success and growth in the utilization of continuous flow ventricular assist devices (cfVADs) for the treatment of advanced heart failure, hemolysis and thrombosis remain major limitations. Inadequate and/or ineffective anticoagulation regimens, combined with high pump speed and non-physiological flow patterns, can result in hemolysis which often is accompanied by pump thrombosis. An unexpected increase in cfVADs thrombosis was reported by multiple major VAD implanting centers in 2014, highlighting the association of hemolysis and a rise in lactate dehydrogenase (LDH) presaging thrombotic events. It is well established that thrombotic complications arise from the abnormal shear stresses generated by cfVADs. What remains unknown is the link between cfVAD-associated hemolysis and pump thrombosis. Can hemolysis of red blood cells (RBCs) contribute to platelet aggregation, thereby, facilitating prothrombotic complications in cfVADs? Herein, we examine the effect of R...

Artificial Organs, 2015

The use of mechanical circulatory support to treat patients with congestive heart failure has gro... more The use of mechanical circulatory support to treat patients with congestive heart failure has grown enormously, recently surpassing the number of annual heart transplants worldwide. The current generation of left ventricular assist devices (LVADs), as compared with older devices, is characterized by improved technologies and reduced size. The result is that minimally invasive surgery is now possible for the implantation, explantation, and exchange of LVADs. Minimally invasive procedures improve surgical outcome; for example, they lower the rates of operative complications (such as bleeding or wound infection). The miniaturization of LVADs will continue, so that minimally invasive techniques will be used for most implantations in the future. In this article, we summarize and describe minimally invasive state-of-the-art implantation techniques, with a focus on the most common LVAD systems in adults.

Perfusion, 2007

A 36-year-old female with hemoglobin Nottingham (betaFG 5(98) Val --> Gly) causing severe hemo... more A 36-year-old female with hemoglobin Nottingham (betaFG 5(98) Val --> Gly) causing severe hemolytic anemia and chronic thromboembolic pulmonary hypertension presented with symptomatic subacute right lower lobar pulmonary arterial thrombosis requiring surgical pulmonary thrombectomy. We describe a successful, multidisciplinary approach to the problems associated with this disease, particularly with the use of cardiopulmonary bypass and deep hypothermic circulatory arrest.

Artificial Organs, 2014

The new generation of left ventricular assist devices has enabled minimally invasive surgical pro... more The new generation of left ventricular assist devices has enabled minimally invasive surgical procedures. Herein we present a novel technique of left ventricular assist device exchange through a left-sided anterolateral thoracotomy.

Pediatric Blood & Cancer, 2014

Chronic myeloid leukemia (CML) is a clonal myeloproliferative disorder of the hematopoietic stem ... more Chronic myeloid leukemia (CML) is a clonal myeloproliferative disorder of the hematopoietic stem cell that is exceptionally rare in the first five years of life, particularly as a secondary malignancy. This report describes a case of secondary CML in a four-year-old female occurring after AML treatment. Interestingly, CML developed while on immunosuppression for a heart transplant due to anthracycline-induced cardiomyopathy.

Circulation. Heart failure, 2014

Mortality for refractory cardiogenic shock remains high. In this patient cohort, there have been ... more Mortality for refractory cardiogenic shock remains high. In this patient cohort, there have been mixed results in mechanical circulatory support device use as a bridge-to-decision therapy. We evaluated a continuous-flow external ventricular assist device (VAD), CentriMag VAD (Thoratec Corp., Pleasanton, CA), in patients with various causes of refractory cardiogenic shock. This is a retrospective review of adult patients who underwent surgical CentriMag VAD insertion as bridge-to-decision therapy. From January 2007 through June 2012, 143 patients received CentriMag VAD. The cause of refractory cardiogenic shock was failure of medical management in 71 patients, postcardiotomy shock in 37, graft failure post-heart transplantation in 22, and right ventricular failure post-implantable left VAD in 13. Mean age was 52±16 years, and 71% were in INTERMACS (Interagency Registry for Mechanically Assisted Circulatory Support) profile 1. Among 158 device runs, device configuration was BiVAD in 6...

Transplantation, 2010

Objectives-Mixed hematopoietic chimerism is associated with islet allograft tolerance and may rev... more Objectives-Mixed hematopoietic chimerism is associated with islet allograft tolerance and may reverse autoimmunity. We developed low intensity regimens for the induction of mixed chimerism and examined effects on autoimmunity in pre-diabetic NOD mice.

Proceedings of the National Academy of Sciences, 2014

Here, we report advanced materials and devices that enable highefficiency mechanical-to-electrica... more Here, we report advanced materials and devices that enable highefficiency mechanical-to-electrical energy conversion from the natural contractile and relaxation motions of the heart, lung, and diaphragm, demonstrated in several different animal models, each of which has organs with sizes that approach human scales. A cointegrated collection of such energy-harvesting elements with rectifiers and microbatteries provides an entire flexible system, capable of viable integration with the beating heart via medical sutures and operation with efficiencies of ∼2%. Additional experiments, computational models, and results in multilayer configurations capture the key behaviors, illuminate essential design aspects, and offer sufficient power outputs for operation of pacemakers, with or without battery assist.

The Journal of Heart and Lung Transplantation, 2004

roughly equivalent to the number of deaths attributed to CAV (Hosenpud J et al. J Heart Lung Tran... more roughly equivalent to the number of deaths attributed to CAV (Hosenpud J et al. J Heart Lung Transplant 2001;20:805-815). According to data from the CTRD (Kirklin J et al. J Thor Cardiovasc Surg 2003;125:881-90), malignancy is the leading cause of death among long-term survivors.

The Journal of Heart and Lung Transplantation, 2013

ABSTRACT

Journal of Cardiothoracic Surgery, 2012

Background: The impact of patient-prosthesis mismatch (PPM) on early outcomes in young and middle... more Background: The impact of patient-prosthesis mismatch (PPM) on early outcomes in young and middle-aged patients undergoing conventional aortic valve replacement for severe aortic stenosis remains unknown. Our objective was to evaluate the incidence of some degree of PPM and its influence on early mortality and morbidity. Methods: We analyzed our single center experience in all patients <70 years undergoing first-time isolated aortic valve replacement for severe stenosis in our center from September 2007 to September 2011. PPM was defined as an indexed effective orifice area ≤ 0,85 cm 2 /m 2 . The influence of PPM on early mortality and postoperative complications was studied using propensity score analysis. Follow up at 30 postoperative days was 100% complete. Results: Of 199 patients studied, 61 (30,7%) had some degree of PPM. PPM was associated with an increased postoperative mortality (OR = 8,71; 95% CI = 1,67-45,29; p = 0,04) and major postoperative complications (OR = 2,96; CI = 1,03-8,55; p = 0,044). However, no association between PPM and prolonged hospital or ICU stay was demonstrated. Conclusions: Moderate PPM is a common finding in young and middle-aged patients undergoing surgery for aortic valve replacement due to severe stenosis. In addition, its influence on early outcomes may be relevant.

Journal of Cardiac Surgery, 2013

Left ventricular assist device (LVAD) pocket infection is a serious and potentially fatal complic... more Left ventricular assist device (LVAD) pocket infection is a serious and potentially fatal complication. Not infrequently, the device erodes externally through the thoracoabdominal wall or internally into the peritoneum. In this article, we report two cases to illustrate the presentation and challenges associated with management of LVAD-pocket infection and wound necrosis. Afterward, we review the current therapeutic strategies for LVAD erosion.

Journal of cardiothoracic surgery, Jan 4, 2016

Right ventricular failure is a serious complication after left ventricular assist device placemen... more Right ventricular failure is a serious complication after left ventricular assist device placement. A 70-year-old male in decompensated heart failure with right ventricular failure after the placement of a left ventricular assist device. A single dual-lumen PROTEKDuo cannula was inserted percutaneously via the internal jugular vein to draw blood from the right atrium and return into the pulmonary artery using the CentriMag system, by passing the failing ventricle. The patient was successfully weaned from right ventricular assist device. In comparison to two-cannula conventional procedures, this right ventrivular assist device system improves patient rehabilitation and minimizes blood loss and risk of infection, while shortening procedure time and improving clinical outcomes in right ventricular failure.

Journal of cardiovascular translational research, 2016

The traditional philosophy of ex vivo organ preservation has been to limit metabolic activity by ... more The traditional philosophy of ex vivo organ preservation has been to limit metabolic activity by storing organs in hypothermic, static conditions. This methodology cannot provide longevity of hearts for more than 4-6 h and is thereby insufficient to expand the number of available organs. Albeit at lower rate, the breakdown of ATP still occurs during hypothermia. Furthermore, cold static preservation does not prevent the permanent damage that occurs upon reperfusion known as ischemia-reperfusion (IR) injury. This damage is caused by increased reactive oxygen species (ROS) production in combination with mitochondrial permeability transition pore (mPTP) opening, highlighting the importance of mitochondria in ischemic storage. There has recently been a major paradigm shift in the field, with emerging research supporting changes in traditional storage approaches. Novel research suggests achieving metabolic homeostasis instead of attempting to limit metabolic activity which reduces IR inj...

Circulation, Nov 26, 2013

SpringerPlus, 2016

Transmyocardial revascularization (TMR) has emerged as an additional therapeutic option for patie... more Transmyocardial revascularization (TMR) has emerged as an additional therapeutic option for patients suffering from diffuse coronary artery disease (CAD), providing immediate angina relief. Recent studies indicate that the volume of surgical cases being performed with TMR have been steadily rising, utilizing TMR as an adjunctive therapy. Therefore the purpose of this review is to provide an up-to-date appreciation of the current state of TMR and its future developmental directions on CAD treatment. The current potential of this therapy focuses on the implementation of stem cells, in order to create a synergistic angiogenic effect while increasing myocardial repair and regeneration. Although TMR procedures provide increased vascularization within the myocardium, patients suffering from ischemic cardiomyopathy may not benefit from angiogenesis alone. Therefore, the goal of introducing stem cells is to restore the functional state of a failing heart by providing these cells with a favo...

Data Revues 00029149 Unassign S000291491302465x, Jan 20, 2014

Mitral valve repair for mitral regurgitation (MR) is currently recommended based on the degree of... more Mitral valve repair for mitral regurgitation (MR) is currently recommended based on the degree of MR and left ventricular (LV) function. The present study examines predictors of reverse remodeling after repair for degenerative disease. We retrospectively identified 439 patients who underwent repair for myxomatous mitral valve degeneration and had both pre-and postoperative echocardiographic data available. Patients were categorized based on left atrial (LA) diameter and LV diameter standards of the American Society of Echocardiography. The outcome of interest was the degree of reverse remodeling on all heart dimensions at follow-up. Mean age was 57 -12 years, and 37% of patients were women. Mean preoperative LV end-diastolic diameter was 5.8 -0.7 cm, LV end-systolic diameter 3.5 -0.6 cm, LA 4.7 -0.7 cm, and median ejection fraction 60%. Median observation time was 81 months, and time to postoperative echocardiography was 38 months. Overall, 95% of patients had normal LV diastolic dimensions postoperatively, 93% normal LV systolic dimensions, and 37% normal LA dimensions. A Cox regression analysis showed that moderate (odds ratio [OR] 2.1, 95% confidence interval [CI] 1.3 to 3.4) or severe preoperative LA dilatation (OR 2.7, 95% CI 1.7 to 4.4), abnormal preoperative LV end-systolic dimensions (OR 1.3, 95% CI 1.1 to 1.5), and age in years (OR 1.02, 95% CI 1.01 to 1.03) were predictive of less reverse remodeling on follow-up. In conclusion, preoperative LV end-systolic dimensions and LA dilatation substantially affect the likelihood of successful LA remodeling and normalization of all heart dimensions after mitral valve repair for MR. These findings support early operation for MR before the increase in heart dimensions is nonreversible. Ó 2014 Elsevier Inc. All rights reserved. (Am J Cardiol 2014;113:1006e1010)

Circulation, Nov 22, 2011

The Faseb Journal, Apr 1, 2013

Transplantation, 2010

Objectives-Mixed hematopoietic chimerism is associated with islet allograft tolerance and may rev... more Objectives-Mixed hematopoietic chimerism is associated with islet allograft tolerance and may reverse autoimmunity. We developed low intensity regimens for the induction of mixed chimerism and examined effects on autoimmunity in pre-diabetic NOD mice.

Perfusion, Jan 20, 2015

Despite the clinical success and growth in the utilization of continuous flow ventricular assist ... more Despite the clinical success and growth in the utilization of continuous flow ventricular assist devices (cfVADs) for the treatment of advanced heart failure, hemolysis and thrombosis remain major limitations. Inadequate and/or ineffective anticoagulation regimens, combined with high pump speed and non-physiological flow patterns, can result in hemolysis which often is accompanied by pump thrombosis. An unexpected increase in cfVADs thrombosis was reported by multiple major VAD implanting centers in 2014, highlighting the association of hemolysis and a rise in lactate dehydrogenase (LDH) presaging thrombotic events. It is well established that thrombotic complications arise from the abnormal shear stresses generated by cfVADs. What remains unknown is the link between cfVAD-associated hemolysis and pump thrombosis. Can hemolysis of red blood cells (RBCs) contribute to platelet aggregation, thereby, facilitating prothrombotic complications in cfVADs? Herein, we examine the effect of R...

Artificial Organs, 2015

The use of mechanical circulatory support to treat patients with congestive heart failure has gro... more The use of mechanical circulatory support to treat patients with congestive heart failure has grown enormously, recently surpassing the number of annual heart transplants worldwide. The current generation of left ventricular assist devices (LVADs), as compared with older devices, is characterized by improved technologies and reduced size. The result is that minimally invasive surgery is now possible for the implantation, explantation, and exchange of LVADs. Minimally invasive procedures improve surgical outcome; for example, they lower the rates of operative complications (such as bleeding or wound infection). The miniaturization of LVADs will continue, so that minimally invasive techniques will be used for most implantations in the future. In this article, we summarize and describe minimally invasive state-of-the-art implantation techniques, with a focus on the most common LVAD systems in adults.

Perfusion, 2007

A 36-year-old female with hemoglobin Nottingham (betaFG 5(98) Val --> Gly) causing severe hemo... more A 36-year-old female with hemoglobin Nottingham (betaFG 5(98) Val --> Gly) causing severe hemolytic anemia and chronic thromboembolic pulmonary hypertension presented with symptomatic subacute right lower lobar pulmonary arterial thrombosis requiring surgical pulmonary thrombectomy. We describe a successful, multidisciplinary approach to the problems associated with this disease, particularly with the use of cardiopulmonary bypass and deep hypothermic circulatory arrest.

Artificial Organs, 2014

The new generation of left ventricular assist devices has enabled minimally invasive surgical pro... more The new generation of left ventricular assist devices has enabled minimally invasive surgical procedures. Herein we present a novel technique of left ventricular assist device exchange through a left-sided anterolateral thoracotomy.

Pediatric Blood & Cancer, 2014

Chronic myeloid leukemia (CML) is a clonal myeloproliferative disorder of the hematopoietic stem ... more Chronic myeloid leukemia (CML) is a clonal myeloproliferative disorder of the hematopoietic stem cell that is exceptionally rare in the first five years of life, particularly as a secondary malignancy. This report describes a case of secondary CML in a four-year-old female occurring after AML treatment. Interestingly, CML developed while on immunosuppression for a heart transplant due to anthracycline-induced cardiomyopathy.

Circulation. Heart failure, 2014

Mortality for refractory cardiogenic shock remains high. In this patient cohort, there have been ... more Mortality for refractory cardiogenic shock remains high. In this patient cohort, there have been mixed results in mechanical circulatory support device use as a bridge-to-decision therapy. We evaluated a continuous-flow external ventricular assist device (VAD), CentriMag VAD (Thoratec Corp., Pleasanton, CA), in patients with various causes of refractory cardiogenic shock. This is a retrospective review of adult patients who underwent surgical CentriMag VAD insertion as bridge-to-decision therapy. From January 2007 through June 2012, 143 patients received CentriMag VAD. The cause of refractory cardiogenic shock was failure of medical management in 71 patients, postcardiotomy shock in 37, graft failure post-heart transplantation in 22, and right ventricular failure post-implantable left VAD in 13. Mean age was 52±16 years, and 71% were in INTERMACS (Interagency Registry for Mechanically Assisted Circulatory Support) profile 1. Among 158 device runs, device configuration was BiVAD in 6...

Transplantation, 2010

Objectives-Mixed hematopoietic chimerism is associated with islet allograft tolerance and may rev... more Objectives-Mixed hematopoietic chimerism is associated with islet allograft tolerance and may reverse autoimmunity. We developed low intensity regimens for the induction of mixed chimerism and examined effects on autoimmunity in pre-diabetic NOD mice.

Proceedings of the National Academy of Sciences, 2014

Here, we report advanced materials and devices that enable highefficiency mechanical-to-electrica... more Here, we report advanced materials and devices that enable highefficiency mechanical-to-electrical energy conversion from the natural contractile and relaxation motions of the heart, lung, and diaphragm, demonstrated in several different animal models, each of which has organs with sizes that approach human scales. A cointegrated collection of such energy-harvesting elements with rectifiers and microbatteries provides an entire flexible system, capable of viable integration with the beating heart via medical sutures and operation with efficiencies of ∼2%. Additional experiments, computational models, and results in multilayer configurations capture the key behaviors, illuminate essential design aspects, and offer sufficient power outputs for operation of pacemakers, with or without battery assist.

The Journal of Heart and Lung Transplantation, 2004

roughly equivalent to the number of deaths attributed to CAV (Hosenpud J et al. J Heart Lung Tran... more roughly equivalent to the number of deaths attributed to CAV (Hosenpud J et al. J Heart Lung Transplant 2001;20:805-815). According to data from the CTRD (Kirklin J et al. J Thor Cardiovasc Surg 2003;125:881-90), malignancy is the leading cause of death among long-term survivors.

The Journal of Heart and Lung Transplantation, 2013

ABSTRACT

Journal of Cardiothoracic Surgery, 2012

Background: The impact of patient-prosthesis mismatch (PPM) on early outcomes in young and middle... more Background: The impact of patient-prosthesis mismatch (PPM) on early outcomes in young and middle-aged patients undergoing conventional aortic valve replacement for severe aortic stenosis remains unknown. Our objective was to evaluate the incidence of some degree of PPM and its influence on early mortality and morbidity. Methods: We analyzed our single center experience in all patients <70 years undergoing first-time isolated aortic valve replacement for severe stenosis in our center from September 2007 to September 2011. PPM was defined as an indexed effective orifice area ≤ 0,85 cm 2 /m 2 . The influence of PPM on early mortality and postoperative complications was studied using propensity score analysis. Follow up at 30 postoperative days was 100% complete. Results: Of 199 patients studied, 61 (30,7%) had some degree of PPM. PPM was associated with an increased postoperative mortality (OR = 8,71; 95% CI = 1,67-45,29; p = 0,04) and major postoperative complications (OR = 2,96; CI = 1,03-8,55; p = 0,044). However, no association between PPM and prolonged hospital or ICU stay was demonstrated. Conclusions: Moderate PPM is a common finding in young and middle-aged patients undergoing surgery for aortic valve replacement due to severe stenosis. In addition, its influence on early outcomes may be relevant.

Journal of Cardiac Surgery, 2013

Left ventricular assist device (LVAD) pocket infection is a serious and potentially fatal complic... more Left ventricular assist device (LVAD) pocket infection is a serious and potentially fatal complication. Not infrequently, the device erodes externally through the thoracoabdominal wall or internally into the peritoneum. In this article, we report two cases to illustrate the presentation and challenges associated with management of LVAD-pocket infection and wound necrosis. Afterward, we review the current therapeutic strategies for LVAD erosion.

Journal of cardiothoracic surgery, Jan 4, 2016

Right ventricular failure is a serious complication after left ventricular assist device placemen... more Right ventricular failure is a serious complication after left ventricular assist device placement. A 70-year-old male in decompensated heart failure with right ventricular failure after the placement of a left ventricular assist device. A single dual-lumen PROTEKDuo cannula was inserted percutaneously via the internal jugular vein to draw blood from the right atrium and return into the pulmonary artery using the CentriMag system, by passing the failing ventricle. The patient was successfully weaned from right ventricular assist device. In comparison to two-cannula conventional procedures, this right ventrivular assist device system improves patient rehabilitation and minimizes blood loss and risk of infection, while shortening procedure time and improving clinical outcomes in right ventricular failure.

Journal of cardiovascular translational research, 2016

The traditional philosophy of ex vivo organ preservation has been to limit metabolic activity by ... more The traditional philosophy of ex vivo organ preservation has been to limit metabolic activity by storing organs in hypothermic, static conditions. This methodology cannot provide longevity of hearts for more than 4-6 h and is thereby insufficient to expand the number of available organs. Albeit at lower rate, the breakdown of ATP still occurs during hypothermia. Furthermore, cold static preservation does not prevent the permanent damage that occurs upon reperfusion known as ischemia-reperfusion (IR) injury. This damage is caused by increased reactive oxygen species (ROS) production in combination with mitochondrial permeability transition pore (mPTP) opening, highlighting the importance of mitochondria in ischemic storage. There has recently been a major paradigm shift in the field, with emerging research supporting changes in traditional storage approaches. Novel research suggests achieving metabolic homeostasis instead of attempting to limit metabolic activity which reduces IR inj...

Circulation, Nov 26, 2013

SpringerPlus, 2016

Transmyocardial revascularization (TMR) has emerged as an additional therapeutic option for patie... more Transmyocardial revascularization (TMR) has emerged as an additional therapeutic option for patients suffering from diffuse coronary artery disease (CAD), providing immediate angina relief. Recent studies indicate that the volume of surgical cases being performed with TMR have been steadily rising, utilizing TMR as an adjunctive therapy. Therefore the purpose of this review is to provide an up-to-date appreciation of the current state of TMR and its future developmental directions on CAD treatment. The current potential of this therapy focuses on the implementation of stem cells, in order to create a synergistic angiogenic effect while increasing myocardial repair and regeneration. Although TMR procedures provide increased vascularization within the myocardium, patients suffering from ischemic cardiomyopathy may not benefit from angiogenesis alone. Therefore, the goal of introducing stem cells is to restore the functional state of a failing heart by providing these cells with a favo...

Data Revues 00029149 Unassign S000291491302465x, Jan 20, 2014

Mitral valve repair for mitral regurgitation (MR) is currently recommended based on the degree of... more Mitral valve repair for mitral regurgitation (MR) is currently recommended based on the degree of MR and left ventricular (LV) function. The present study examines predictors of reverse remodeling after repair for degenerative disease. We retrospectively identified 439 patients who underwent repair for myxomatous mitral valve degeneration and had both pre-and postoperative echocardiographic data available. Patients were categorized based on left atrial (LA) diameter and LV diameter standards of the American Society of Echocardiography. The outcome of interest was the degree of reverse remodeling on all heart dimensions at follow-up. Mean age was 57 -12 years, and 37% of patients were women. Mean preoperative LV end-diastolic diameter was 5.8 -0.7 cm, LV end-systolic diameter 3.5 -0.6 cm, LA 4.7 -0.7 cm, and median ejection fraction 60%. Median observation time was 81 months, and time to postoperative echocardiography was 38 months. Overall, 95% of patients had normal LV diastolic dimensions postoperatively, 93% normal LV systolic dimensions, and 37% normal LA dimensions. A Cox regression analysis showed that moderate (odds ratio [OR] 2.1, 95% confidence interval [CI] 1.3 to 3.4) or severe preoperative LA dilatation (OR 2.7, 95% CI 1.7 to 4.4), abnormal preoperative LV end-systolic dimensions (OR 1.3, 95% CI 1.1 to 1.5), and age in years (OR 1.02, 95% CI 1.01 to 1.03) were predictive of less reverse remodeling on follow-up. In conclusion, preoperative LV end-systolic dimensions and LA dilatation substantially affect the likelihood of successful LA remodeling and normalization of all heart dimensions after mitral valve repair for MR. These findings support early operation for MR before the increase in heart dimensions is nonreversible. Ó 2014 Elsevier Inc. All rights reserved. (Am J Cardiol 2014;113:1006e1010)

Circulation, Nov 22, 2011

The Faseb Journal, Apr 1, 2013