Entela B. Lushaj

Hospital Readmissions After Continuous-Flow Left Ventricular Assist Device Implantation: Incidence, Causes, and Cost Analysis

BACKGROUND We investigated the incidence and causes of unplanned hospital readmissions after continuous-flow (CF) left ventricular assist device (LVAD) implantation. We also analyzed the impact of unplanned readmissions on post-CF-LVAD survival and the costs associated with each cause of readmission. METHODS We retrospectively reviewed 126 patients who underwent implantation with a CF-LVAD from January 2007 to December 2013. The timing of readmissions, hospital length of stay, and total length of device support were evaluated. Patients were followed up while receiving support, until transplantation, or until death. Direct hospital costs associated with each readmission were analyzed. RESULTS In all, 103 patients underwent implantation for bridge to transplantation and 19 patients for destination therapy; 68 patients were readmitted 156 times (2.2 times/patient) as of the end of follow-up. The median follow-up period was 11 months. While receiving device support, patients spent 93% of their time out of the hospital. The causes of readmission included gastrointestinal bleeding (19%), driveline infection (13%), and stroke (8%). The median time to first readmission was 35 days. Thirty (44%) patients were readmitted within 30 days after discharge. The median direct hospital cost of a single readmission was

Mesenchymal stromal cells are present in the heart and promote growth of adult stem cells in vitro

7,546. Device malfunction and arrhythmias were the most costly causes of readmission. There was no significant difference in long-term survival between readmitted patients and those who were not readmitted. CONCLUSIONS Gastrointestinal bleeding and CF-LVAD-related infections were the leading causes of readmission. Patients with a CF-LVAD spent 93% of their time out of hospital after implantation, and readmissions did not have a negative impact on long-term survival. New approaches to minimize these adverse events will continue to improve the efficacy and decrease the cost of CF-LVAD therapy.

Functional evaluation of human donation after cardiac death donor hearts using a continuous isolated myocardial perfusion technique: Potential for expansion of the cardiac donor population

BACKGROUND AIMS For many years the human heart has been considered a terminally differentiated organ with no regenerative potential after injury. Recent studies, however, have cast doubt on this long-standing dogma. The objective of this study was to investigate the presence of and characterize mesenchymal stromal cells (MSC) in the adult mouse heart. The impact of MSC on growth and differentiation of adult cardiac stem cells (CSC) was also analyzed. METHODS A combination of lineage-negative/c-kit-negative (Lin(-)/c-kit(-)) immunoselection with a plastic-adhesion technique was used to isolate cardiac-derived MSC. The differentiation capacity and expression of surface markers were analyzed. To investigate the impact of MSC on growth and differentiation of adult CSC, Green Fluorescent Protein (GFP(+)) adult CSC were co-cultured with GFP(-) cardiac-derived MSC. RESULTS MSC were present in the adult mouse heart and they met the criteria established to define mouse MSC. They expressed surface markers and were able to differentiate, in a controlled manner, into multiple lineages. In addition, cardiac-derived MSC promoted the survival and expansion of adult CSC in vitro. CONCLUSIONS MSC can be isolated from the mouse heart and they promote growth and differentiation of adult CSC. The findings from this study could have a significant beneficial impact on future heart failure treatment. Co-culture and co-implantation of cardiac-derived MSC with adult CSC could provide extensive cardiac regeneration and maintenance of the CSC population after implanted into the heart.

Impact of age on outcomes following continuous-flow left ventricular assist device implantation

OBJECTIVE To investigate the resuscitation potential and contractile function in adult human donation after cardiac death (DCD) hearts by ex vivo perfusion. METHODS With institutional review board approval and under the DCD protocol at the University of Wisconsin (UW) Organ Procurement Organization, 5 brain dead (BD) and 5 DCD donor hearts were evaluated. All BD hearts were declined for clinical transplantation because of coronary artery disease, advanced age, or social history. All hearts were preserved by flushing and cold storage with UW solution. By using our ex vivo perfusion system, the left ventricular end systolic pressure-volume relationship (LV-ESPVR) was assessed for 2 hours of oxygenated blood reperfusion. RESULTS All BD (n = 5) and 4 DCD hearts were successfully resuscitated. One DCD heart was unable to be resuscitated due to prolonged warm ischemic time (WIT; 174 minutes). Mean WIT for resuscitated DCD hearts (from extubation to flushing with cold UW solution) was 34 ± 3 minutes (range, 26 to 40 minutes); mean cold ischemic time for BD donors was 211 ± 31 minutes compared with 177 ± 64 minutes for DCD donors. The calculated LV-ESPVRs for BD hearts after 1 and 2 hours of reperfusion were 6.9 ± 0.7 and 5.7 ± 1.0 mm Hg/mL, respectively; LV-ESPVRs for DCD hearts after 1 and 2 hours of reperfusion were 5.6 ± 1.5 (P = .45) and 3.0 ± 0.7 mm Hg/mL (P = .07), respectively. CONCLUSIONS We successfully resuscitated and measured ex vivo cardiac function in human DCD and BD donor hearts. Resuscitation potential in DCD hearts was achieved when the WIT was less than 40 minutes. Contractile performance in DCD hearts tended to be lower compared with BD hearts. Further investigation with longer reperfusion periods seems warranted.

To use or not to use? Amiodarone before heart transplantation

OBJECTIVES The goal of our study was to analyse the impact of age on outcomes in patients who underwent continuous-flow left ventricular assist device (CF-LVAD) placement at our institution. METHODS One hundred and twenty-eight patients were implanted with a CF-LVAD between January 2008 and June 2014. Eighty-five patients were implanted with the device as a bridge to transplant (BTT); the remaining (n = 43) were on destination therapy (DT). Each group was divided into patients <65 years old and ≥ 65 years old at device implantation. Patients were followed up for at least 24 months or until transplant or death. RESULTS Eighty-five patients (66%) received a CF-LVAD as BTT. Patients ≥ 65 years old (n = 8) had a lower preoperative cardiac index and prothrombin time-international normalized ratio (P = 0.009), and a longer stay in the intensive care unit (P = 0.008). Adverse events including infections, re-exploration for bleeding, ischaemic and haemorrhagic stroke, renal failure and right heart failure were comparable in both age groups. Eighty-two percent (n = 63) of the young patients and 75% (n = 6) of the older patients, who were on LVAD as BTT, underwent heart transplant within the first 24 months of LVAD implantation. Overall survival at 3, 6, 12 and 24 months were 95, 95, 77 and 70%, respectively, post-CF-LVAD implantation as BTT for the younger group and 73% for the older group at 3, 6 and 12 months (P = 0.35). Forty-three patients (34%) received a CF-LVAD as DT. Patients ≥ 65 years old (n = 14) on DT had a higher incidence of peripheral vascular disease (P = 0.048), higher serum sodium (P = 0.004) and serum creatinine values (P = 0.002), preoperatively. There were more strokes in the older patients post-LAVD implantation (14 vs 0%; P = 0.048). Overall survival at 3, 6, 12 and 24 months were 85, 79, 75 and 62%, respectively, for the younger group and 93, 77, 67 and 34% for the older group, respectively (P = 0.26). CONCLUSIONS This study demonstrates that LVAD therapy can be used in the older patients with acceptable mortality and morbidity, and age alone should not be used as the sole criterion for exclusion from LVAD implantation.

Mitochondrial DNA deletion mutations in adult mouse cardiac side population cells

Background. Amiodarone frequently is used in patients with heart failure. Concerns still exist about possible complications related to its lingering effect during and after heart transplantation. Methods. We selected all consecutive patients who received a heart transplant at our institution between January 2004 and December 2015 (n = 220) and compared the peri‐ and postoperative outcomes of patients who were taking amiodarone for at least 120 days before heart transplant (n = 127) with patients who did not take amiodarone prior to heart transplant (n = 93). Results. Compared with patients with no amiodarone use prior to transplant, those who had used amiodarone were similar in age, body mass index, sex, cause of cardiomyopathy, prevalence of diabetes, hypertension, presence of defibrillator, and had similar donor ischemic times during transplant (all P > .05). Median operative time, aortic cross clamp time, mechanical ventilation and median hospital duration of stay did not differ between the 2 groups (P > .05). Patients exposed to amiodarone had fewer cellular rejections (5% vs 20%; P = .001) but more primary graft dysfunction (4% vs 0%; P = .025) and post‐transplant pneumonia (P = .047) compared with patients not taking amiodarone prior to transplant. Both groups had similar rate of atrial fibrillation, 30‐day readmission, and 30‐day mortality (P > .05). Even though 1‐year survival was not affected by amiodarone use (P = .51), long‐term (5‐year) survival was significantly less in patients exposed to amiodarone (P = .03). Conclusion. Amiodarone use did not affect the incidence of atrial fibrillation nor 30‐day and 1‐year survival post‐transplantation. Nevertheless, post‐transplant pulmonary complications were significantly greater and 5‐year survival was less among patients treated with amiodarone prior to transplant.

Digital PCR Quantitation of Muscle Mitochondrial DNA: Age, Fiber Type, and Mutation-Induced Changes

We investigated the presence and potential role of mitochondrial DNA (mtDNA) deletion mutations in adult cardiac stem cells. Cardiac side population (SP) cells were isolated from 12-week-old mice. Standard polymerase chain reaction (PCR) was used to screen for the presence of mtDNA deletion mutations in (a) freshly isolated SP cells and (b) SP cells cultured to passage 10. When present, the abundance of mtDNA deletion mutation was analyzed in single cell colonies. The effect of different levels of deletion mutations on SP cell growth and differentiation was determined. MtDNA deletion mutations were found in both freshly isolated and cultured cells from 12-week-old mice. While there was no significant difference in the number of single cell colonies with mtDNA deletion mutations from any of the groups mentioned above, the abundance of mtDNA deletion mutations was significantly higher in the cultured cells, as determined by quantitative PCR. Within a single clonal cell population, the detectable mtDNA deletion mutations were the same in all cells and unique when compared to deletions of other colonies. We also found that cells harboring high levels of mtDNA deletion mutations (i.e. where deleted mtDNA comprised more than 60% of total mtDNA) had slower proliferation rates and decreased differentiation capacities. Screening cultured adult stem cells for mtDNA deletion mutations as a routine assessment will benefit the biomedical application of adult stem cells.

A novel approach to prevent post-operative ileus after continuous-flow left ventricular assist device implantation: A retrospective cohort study

Definitive quantitation of mitochondrial DNA (mtDNA) and mtDNA deletion mutation abundances would help clarify the role of mtDNA instability in aging. To more accurately quantify mtDNA, we applied the emerging technique of digital polymerase chain reaction to individual muscle fibers and muscle homogenates from aged rodents. Individual fiber mtDNA content correlated with fiber type and decreased with age. We adapted a digital polymerase chain reaction deletion assay that was accurate in mixing experiments to a mutation frequency of 0.03% and quantitated an age-induced increase in deletion frequency from rat muscle homogenates. Importantly, the deletion frequency measured in muscle homogenates strongly correlated with electron transport chain-deficient fiber abundance determined by histochemical analyses. These data clarify the temporal accumulation of mtDNA deletions that lead to electron chain-deficient fibers, a process culminating in muscle fiber loss.

Intraoperative Completion Angiogram May Be Superior to Transesophageal Echocardiogram for Detection of Pulmonary Artery Residual Lesions in Congenital Heart Surgery

INTRODUCTION Patients with postoperative ileus (POI), a common post-surgical event, experience intense discomfort. Various treatments targeting prevention of POI have shown to have an unpredictable effect. We introduced a novel postoperative bowel management protocol in patients implanted with a continuous-flow left ventricular assist device (CF-LVAD). The effect of this protocol on POI was evaluated. METHODS Patients receiving an old bowel management protocol (OBMP; 01/2007-03/2009) were compared with those receiving a new bowel management protocol (NBMP; 04/2009-12/2013). The OBMP consisted of advancing the diet as tolerated, bisacodyl suppositories and enemas with the goal of a bowel movement (BM) every 3 days. The NBMP consisted of clear liquids until first BM is achieved, then full liquids until the second BM, then advancing to goal diet. Docusate is given on postoperative day (POD) 1 and bisacodyl PR on POD2 with enemas if ileus develops. Enemas are added POD3 if no BM has occurred. Polyethylene glycol is considered daily for patients prone to constipation. The goal is a BM every 2 days. Patients were made nil per os (NPO) with any signs of ileus. RESULTS One hundred eighteen patients were implanted with CF-LVADs during the study period. The incidence of ileus significantly decreased from 19% in the OBMP group to 4% percent in the NBMP group (p < 0.05). In-hospital mortality was not different between the two groups (6% vs. 2% p = 0.35). CONCLUSIONS A novel postoperative bowel management protocol successfully decreased the incidence of POI following CF-LVAD implant surgery at our institution.

Sarcopenia accelerates at advanced ages in Fisher 344xBrown Norway rats.

The purpose of this study was to assess the diagnostic capabilities of transesophageal echocardiography (TEE) compared to completion angiography for detection of residual post-operative pulmonary artery lesions. This is a retrospective review of 19 consecutive surgical cases involving the pulmonary arteries that had post-operative TEE and completion angiography from 2014 to 2017. The echocardiograms were reviewed by 2 blinded examiners and categorized as adequate or inadequate visualization of the surgical repair. Based on TEE images, the surgical repair was graded as no revision necessary, residual lesion present requiring revision, or unable to assess. TEE was compared to completion angiography to determine the ability of each method to detect residual pulmonary artery lesions. Fifty-three percent of TEE imaging was graded as inadequate. Based on TEE, surgical revision was indicated in 2 of 19 cases. Completion angiography documented 4 additional residual lesions resulting in surgical revision in 6 of 19 patients. TEE sensitivity for detecting residual pulmonary artery lesions was 40%. One Glenn patient with adequate image quality and repair by TEE had moderate left pulmonary artery stenosis by completion angiography. All other discrepancies occurred in patients with inadequate TEE imaging. No patient with pulmonary artery abnormalities had hemodynamic instability or excessive desaturations. Completion angiography-related complications included three transient arrhythmias with no increased incidence of acute kidney injury. Completion angiography may be more effective than TEE at detecting post-operative pulmonary artery lesions even in patients not manifesting clinical symptoms. Documentation of residual lesions with completion angiography allows immediate surgical revision potentially limiting necessity for future interventions.