Implantation of a left ventricular assist device (LVAD) is a potential treatment in terminal heart failure. Right ventricular (RV) failure is a severe complication in these patients and sometimes requires additional placement of a right ventricular assist device (RVAD). RVAD implantation, however, is an invasive treatment associated with both increased mortality and morbidity. The aim of this thesis was to study whether partial volume exclusion of the RV through a modified Glenn shunt or cavoaortic shunt could treat severe RV failure. The ultimate goal would be to use it as an alternative to a RVAD in RV failure during LVAD therapy. Swine were used as the model animal in all studies. In Study I, experimental RV failure was induced by ischemia, and verified by hemodynamic measurements and genetic expression. Treatment with a modified Glenn shunt reduced venous stasis and improved hemodynamics in general. In Study II, experimental RV failure was induced by the same method as in Study I. Treatment with a cavoaortic shunt in addition to LVAD therapy proved to reduce venous stasis and improved hemodynamics in general, which was feasible with preserved oxygen delivery despite cyanotic shunting. In Study III, experimental RV failure was induced by pulmonary banding, and verified by hemodynamic measurements and genetic expression. Treatment with a modified Glenn shunt reduced venous stasis but did not improve hemodynamics in general compared with a control group. In Study IV, the effects of LVAD therapy and subsequent treatment with a modified Glenn shunt on the normal RV function were studied. It demonstrated that LVAD therapy can put strain on the RV by increasing stroke work and end-diastolic volume, and that these effects can be reversed by treatment with a modified Glenn shunt during LVAD therapy. In conclusion, partial volume exclusion through a modified Glenn shunt or cavoaortic shunt is a feasible treatment of experimental RV failure. Thus, it could potentially be used as an alternative treatment to a RVAD in severe RV failure during LVAD therapy.

Pump thrombosis is the epitome of left ventricular assist device dysfunction for end-stage heart failure patients. With the increased utilization of implantable, long-term, left ventricular assist devices (LVADs), understanding the implications associated with device orientation and interaction with the body is exceedingly important. Components associated with pump thrombosis in the Thoratec© HeartMate II™ (HMII) and the HeartWare© HVAD® devices include the inflow cannula, the outflow graft, and the pump elements as well as pump pocket depth for the HMII specifically. Several studies have been conducted to analyze these interactions with the HMII, however there is minimal to no data available analyzing how the device orientation of the HeartWare HVAD affects hemodynamics and a patient’s risk for developing pump thrombosis. Therefore, the purpose of this pilot study is the simulate the hemodynamic implications associated with Sub-optimal cannula angulation of the HVAD. Using Solidworks 2016 Ed., a simplified, hemo-static model of the left side of the heart was created. Dimensions for the atria, ventricle, and mitral valve were determined through the combination of Trans-Esophageal Echo cardiogram data as well as literature references. Three different inflow cannula angle scenarios were developed including a Control, a Clinically Optimal, and a Sub-optimal. Assumptions included body temperature, no accumulation within the ventricle, and no ejection or contraction. The model consists of static continuous flow set to 5 liters per minute with the assumption that the HeartWare HVAD is completely supporting the left ventricle. The results include both qualitative and quantitative data. Flow trajectory plots for each cannula scenario depict the hemodynamic flow patterns for different time points. Results show visible changes in the Sub-optimal orientation when compared to both the Control and the Clinically Optimal scenario. Additionally, it was determined that there were no statistically significant differences in the velocity vectors for any of the scenarios however, the shear stress values were determined to be significantly different for all time points, p < 0.001 for all scenarios when compared to Control. Though there are several limitations of this study, with sub-optimal inflow cannula angulation, there is a potential increased risk of hemolysis due to increased shear stress.

Background: Aortic valve insufficiency (AI) at the time of left ventricular assist device (LVAD) insertion needs to be corrected, however there is little known about how to manage bioprosthetic valvular AI. Case presentation: A 55-year-old female with dilated cardiomyopathy who previously had a bioprosthetic aortic valve replacement needed a LVAD as a bridge to transplant. Her left ventricular ejection fraction was 10% and had mild to moderate transvalvular AI. She underwent a HeartWare HVAD insertion along with aortic valvular coaptation stitch repair (Park's stitch) to the bioprosthetic valve. Conclusion: Her AI improved to trivial with minimal ejection through the bioprosthetic valve. She was transplanted 6 months following the surgery. A Park's stitch to the bioprosthetic aortic valve with more than mild AI might be a good option for bridge to transplant patient.

Heart failure is a progressive condition that affects over 5.7 million Americans and costs associated with heart failure account for 2-3 % of the national health care budget. The high rates of morbidity and mortality along with increased costs from readmissions associated with advanced heart failure have led to the exploration of advanced treatments such as left ventricular assist devices (LVADs). LVADS have demonstrated morbidity and mortality benefit but cost remains extensive with costs per quality-adjusted years > $400,000. With this in mind, it is important to identify those who are most likely to benefit from an LVAD to avoid unfavorable outcomes and cost. Although general guidelines and criteria for patient eligibility have been established, choosing patients for LVAD implantation remains challenging. A new focus on patient selection involves the presence of frailty. While frailty has been studied in the elderly population and in patients undergoing cardiac surgery, frailty in patients undergoing left ventricular assist device (LVAD) remains controversial. The purpose of this dissertation was to examine measures of frailty in patients undergoing LVAD implantation. The specific aims of this dissertation were to: (1) identify a feasible frailty measure in adults with end-stage heart failure who underwent LVAD implantation by testing the hypothesis that frailty would predict 30 day rehospitalization rates using Fried’s criteria, Short Physical Performance Battery test, handgrip strength, serum albumin and six minute walk test (2) Determine whether frailty measures improve 3 months post LVAD implantation (3) compare sensitivity of these three measures to change in frailty. Surgical approaches, including heart transplantation and LVAD implantation, for patients with end-stage heart failure was discussed in this dissertation. Data from two subsets of participants who underwent LVADS at the University of Kentucky between 2014 and 2017 were included in the analysis for this dissertation. In the first study, we found that none of the measures are good predictors of frailty in patients with advanced heart failure who undergo LVAD implantation. Handgrip was the only marker of frailty that predicted 30 day readmission but the relationship was a negative association. In the second study, six-minute walk and low serum albumin levels reflect short-term improvement in frailty. These simple measures may be used to determine those patients who are responsive to LVAD implantation. The findings of these studies filled some gaps in our understanding of markers of frailty in patients undergoing LVADs. We gained a better understanding of which markers of frailty are likely to improve in most people after LVAD implantation and thus frailty should not preclude candidate selection for an LVAD. Subsequently, more research is needed to investigate these markers and outcomes.

Background: Temporary mechanical circulatory support device without sternotomy has been highly advocated for severe cardiogenic shock patient but little is known when coupled with amniotic stem cell therapy. Case presentation: This case reports the first dual therapy of temporary left ventricular extracorporeal device CentriMag with distal banding technique and human amniotic stem cell injection for treating a severe refractory cardiogenic shock of an 68-year-old female patient. A minimally-invasive off-pump LVAD was established by draining from the left ventricle and returning to the right axillary artery with distal arterial banding to prevent right upper extremity hyperperfusion. Amniotic stem cells were injected intramyocardially at the left ventricular apex, lateral wall, inferior wall, and right subclavian vein. Conclusion: The concomitant use of the temporary minimally-invasive off-pump CentriMag placement and stem cell therapy not only provided an alternative to cardiopulmonary bypass and full-median sternotomy procedures but may have also synergistically enhanced myocardial reperfusion and regeneration.

京都大学 / 新制・論文博士 / 博士(医学) / 乙第13428号 / 論医博第2232号 / 新制||医||1053(附属図書館) / (主査)教授 湊谷 謙司, 教授 佐藤 俊哉, 教授 福田 和彦 / 学位規則第4条第2項該当 / Doctor of Medical Science / Kyoto University / DFAM

This study evaluates the impact of untreated preoperative severe mitral valve regurgitation (MR) on outcomes after left ventricular assist device (LVAD) implantation. Of the 234 patients who received LVAD therapy in the Heart Center Leipzig during a 6-year period, we selected those who had echocardiographic images of good quality and excluded those who underwent mitral valve replacement prior to or mitral valve repair during LVAD placement. The 128 patients selected were divided into 2 groups: Group A with severe MR (n = 65) and Group B with none to moderate MR (n = 63, 28 with moderate MR). We evaluated transthoracic echocardiography preoperatively [15 (7–28) days before LVAD implantation; median (interquartile range)] and postoperatively up to the last available follow-up [501 (283–848) days after LVAD]. We collected mortality, complications and clinical status indicators of the patient cohort. We observed a significant decrease in the severity of MR after LVAD implantation (severe MR 51% pre- vs 6% post-LVAD implantation, P < 0.001). There was no difference between groups in terms of right heart failure, rate of urgent heart transplantation, pump thrombosis or ventricular arrhythmias. There was no difference in 1-year survival and 3-year survival (87.7% vs 88.4% and 71.8% vs 66.6% for Groups A and B, respectively, P = 0.97). We concluded that preoperative severe MR resolves in the majority of patients early on after LVAD implantation and is not associated with worse clinical outcomes or intermediate-term survival.:Inhaltsverzeichnis Abkürzungsverzeichnis 3 1. Einführung 4 2. Formatierte Publikation 12 3. Zusammenfassung der Arbeit 19 4. Literaturverzeichnis 23 5. Anlagen 28 5.1. Statistical analysis of echocardiographic parameters in follow-up 28 5.2. Statistical Models Used 30 Darstellung des eignen wissenschaftlichen Beitrages 32 Erklärung über die eigenständige Abfassung der Arbeit 33 Lebenslauf 34 Publikationen 37 Danksagung 38

The Left Ventricular Assist Device (LVAD) is a rotary mechanical pump that is implanted in patients with congestive heart failure to help the left ventricle in pumping blood in the circulatory system. The rotary type pumps are controlled by varying the pump motor current to adjust the amount of blood flowing through the LVAD. One important challenge in using such a device is the desire to provide the patient with as close to a normal lifestyle as possible until a donor heart becomes available. The development of an appropriate feedback controller that is capable of automatically adjusting the pump current is therefore a crucial step in meeting this challenge. In addition to being able to adapt to changes in the patient's daily activities, the controller must be able to prevent the occurrence of excessive pumping of blood from the left ventricle (a phenomenon known as ventricular suction) that may cause collapse of the left ventricle and damage to the heart muscle and tissues. In this dissertation, we present a new suction detection system that can precisely classify pump flow patterns, based on a Lagrangian Support Vector Machine (LSVM) model that combines six suction indices extracted from the pump flow signal to make a decision about whether the pump is not in suction, approaching suction, or in suction. The proposed method has been tested using in vivo experimental data based on two different LVAD pumps. The results show that the system can produce superior performance in terms of classification accuracy, stability, learning speed, iv and good robustness compared to three other existing suction detection methods and the original SVM-based algorithm. The ability of the proposed algorithm to detect suction provides a reliable platform for the development of a feedback control system to control the current of the pump (input variable) while at the same time ensuring that suction is avoided. Based on the proposed suction detector, a new control system for the rotary LVAD was developed to automatically regulate the pump current of the device to avoid ventricular suction. The control system consists of an LSVM suction detector and a feedback controller. The LSVM suction detector is activated first so as to correctly classify the pump status as No Suction (NS) or Suction (S). When the detection is “No Suction”, the feedback controller is activated so as to automatically adjust the pump current in order that the blood flow requirements of the patient’s body at different physiological states are met according to the patient’s activity level. When the detection is “Suction”, the pump current is immediately decreased in order to drive the pump back to a normal No Suction operating condition. The performance of the control system was tested in simulations over a wide range of physiological conditions.

The aim of this retrospective study was to investigate whether there would be an association between periodontal disease parameters and positive bacterial findings at the driveline of patients with a left ventricular assist device (LVAD). Patients with an LVAD, who underwent a full oral and microbiological examination between 2016 and 2018, were included. During oral examination, periodontitis severity (stage and grade) and the periodontal inflamed surface area (PISA) were evaluated. A microbiological analysis was performed from swabs of the driveline, whereby different bacterial species were cultivated and analyzed. A total of 73 patients were included in the current study. The majority of participants (80.8%) had at least one positive bacterial finding during the study period. Most patients had a periodontitis stage of III-IV (80.9%). The determined PISA of the total group was 284.78 ± 352.29 mm2. No associations were found between the periodontal disease parameters and the bacterial findings in general, the bacterial findings on the day of oral examination or the bacterial findings 12 months prior to/after the oral examination (p > 0.05). Periodontitis is not associated with cultivated microbiological findings at the driveline of patients with an LVAD and thus appears not to be a risk indicator for driveline colonization. Nevertheless, the high periodontal burden in LVAD patients underlines the need for their improved periodontal care.

The rotary Left Ventricular Assist Device (LVAD) is a mechanical pump surgically implanted in patients with end-stage congestive heart failure to help maintain the flow of blood from the sick heart. The rotary type pumps are controlled by varying the impeller speed to control the amount of blood flowing through the LVAD. One important challenge in using these devices is to prevent the occurrence of excessive pumping of blood from the left ventricle (known as suction) that may cause it to collapse due to the high pump speed. The development of a proper feedback controller for the pump speed is therefore crucial to meet this challenge. In this thesis, some theoretical and practical issues related to the development of such a controller are discussed. First, a basic nonlinear, time-varying cardiovascular-LVAD circuit model that will be used to develop the controller is reviewed. Using this model, a suction index is tested to detect suction. Finally we propose a feedback controller that uses the pump flow signal to regulate the pump speed based on the suction index and an associated threshold. The objective of this controller is to continuously update the pump speed to adapt to the physiological changes of the patient while at the same time avoiding suction. Simulation results are presented under different conditions of the patient activities. Robustness of the controller to measurement noise is also discussed.