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To evaluate the hypothesis that weight gain after left ventricular assist device (LVAD) occurs after the nadir of natriuretic peptides (nt-proBNP), and that persistently elevated natriuretic peptides is associated with failure to gain weight after LVAD implantation. Body mass index (BMI) and nt-proBNP trends before and after LVAD in a single center continuous flow cohort (n=505) were computed and plotted using Locally Estimated Scatterplot Smoothing (LOESS). Linear mixed effects modeling was performed to test the association between nt-proBNP and BMI. CT measures of sarcopenia (pectoralis muscle mass index to body surface area and tissue attenuation, n=194) was correlated with pre-LVAD BMI trend. The plots of BMI and log nt-proBNP for the entire cohort before and after LVAD are demonstrated (Figure). The rise in BMI did not occur until after the nadir of post implant nt-proBNP. Downward slope of BMI prior to LVAD was associated with lower pectoralis muscle measures prior to implantation. Patients who failed to gain weight post LVAD had the highest 6 month post LVAD natuetic peptides (lowest pecent BMI gain tertile nt-proBNP: 2,208 vs. highest 1,635 pg/mL, p <0.001). Post LVAD nt-pro BNP and BMI trends were significantly associated (a decrease of 1 unit log nt-proBNP was associated with an increase in 0.81 BMI, 95 % CI: 0.53-1.09, p < 0.001). Weight gain post LVAD did not occur until the nadir of natriuretic peptides. Failure to gain weight post LVAD was associated with persistently elevated natriuretic peptides. These data collectively suggest that gains in body mass may be dependent on resolution of heart failure. [ABSTRACT FROM AUTHOR]

Inherited cardiomyopathies, including hypertrophic cardiomyopathy, dilated cardiomyopathies, arrythmogenic right ventricular cardiomyopathy, and other inherited forms of heart failure, represent a unique set of genetically defined cardiovascular disease processes. Unraveling the molecular mechanisms of these deadly forms of human heart disease has been challenging, but recent groundbreaking scientific advances in stem cell technology have allowed for the generation of patient-specific human inducible stem cell (hiPSC)–derived cardiomyocytes (CMs). hiPSC-derived CMs retain the genetic blueprint of the patient, they can be maintained in culture, and they recapitulate the phenotypic characteristics of the disease in vitro, thus serving as a disease in a dish. This review provides an overview of in vitro modeling of inherited cardiomyopathies with the use of patient-specific hiPSC-derived CMs. [ABSTRACT FROM AUTHOR]

Background. An ongoing challenge in the management of patients with heart failure who receive left ventricular assist devices (LVADs) is achieving optimal anti-coagulation. Adverse prothrombotic events include hemolysis or pump thrombus (H/T) and neurologic events (NEs), and all limit the success of LVAD therapy. Our aim was to study the incidence and clinical outcomes associated with these events in a large single-center cohort. Methods. We retrospectively reviewed our prospectively collected database of all patients receiving a HeartMate II (Thoratec Corp, Pleasanton, CA) LVAD from 2005 to 2012. Demographic, clinical, and outcome data were analyzed using standard statistical methods. All adverse events were recorded. Results. Of 193 patients receiving LVADs, we identified 39 H/T events in 26 (13.4%) patients and 22 NEs in 19 (9.8%) patients. Seventy-four percent of events occurred in the last 3 years of the series, during which time 63% of implants were placed. Of patients with H/T, 8 (31% of those having H/T, 4.1% of total) had more than 1 event and 4 (15.4% of those having H/T, 2.1% of total) underwent pump exchanges. Five (23%) patients had NEs after H/T, and 6 (32%) died as a result of the NE. Of patients with H/T, 27% had preceding episodes of infection, 31% had an international normalized ratio (INR) of less than 1.5, 31% had an INR of 1.5 to 2, 15% had a history of clotting or were hypercoagulable, and 4% had anti-coagulation intentionally withheld. Lactate dehydrogenase (LDH), plasma hemoglobin, INR, and platelet determinations were significantly different at the time of H/T compared with baseline values. The survival at 6 months (alive or having undergone transplantation) for those with a prothrombotic event compared with those without was 70% versus 75.2% (p = 0.5). Conclusions. The incidence of H/T or NEs is significant and results in major morbidity after LVAD placement. Infection and suboptimal anticoagulation are associated with the majority of these events. Identification of patients at higher risk for hemolysis (ie, infection) may allow for modification of anticoagulation regimens to reduce these risks and improve clinical outcomes. [ABSTRACT FROM AUTHOR]

Objectives: Continuous-flow left ventricular assist devices have become the standard of care for patients with heart failure requiring mechanical circulatory support as a bridge to transplant. However, data on long-term post-transplant survival for these patients are limited. We evaluated the effect of continuous-flow left ventricular assist devices on postcardiac transplant survival in the current era. Methods: All patients who received a continuous-flow left ventricular assist device as a bridge to transplant at a single center from June 2005 to September 2011 were evaluated. Results: Of the 167 patients who received a continuous-flow left ventricular assist device as a bridge to transplant, 77 (46%) underwent cardiac transplantation, 27 died before transplantation (16%), and 63 (38%) remain listed for transplantation and continued with left ventricular assist device support. The mean age of the transplanted patients was 54.5 ± 11.9 years, 57% had an ischemic etiology, and 20% were women. The overall mean duration of left ventricular assist device support before transplantation was 310 ± 227 days (range, 67-1230 days). The mean duration of left ventricular assist device support did not change in patients who had received a left ventricular assist device in the early period of the study (2005-2008, n = 62) compared with those who had received a left ventricular assist device later (2009-2011, n = 78, 373 vs 392 days, P = NS). In addition, no difference was seen in survival between those patients supported with a left ventricular assist device for fewer than 180 days or longer than 180 days before transplantation (P = NS). The actuarial survival after transplantation at 30 days and 1, 3, and 5 years by Kaplan-Meier analysis was 98.7%, 93.0%, 91.1%, and 88.0%, respectively. Conclusions: The short- and long-term post-transplant survival for patients bridged with a continuous-flow left ventricular assist device in the current era has been excellent. Furthermore, the duration of left ventricular assist device support did not affect post-transplant survival. The hemodynamic benefits of ventricular unloading with continuous-flow left ventricular assist devices, in addition to their durability and reduced patient morbidity, have contributed to improved post-transplant survival. [Copyright &y& Elsevier]

Background: Continuous-flow left ventricular assist devices (LVADs) such as the HeartMate II have become the therapy of choice in patients with end-stage heart failure. The aim of this study is to report the outcomes in patients receiving the HeartMate II LVAD at a single center and review the lessons learned from this experience. Methods: From June 2005 to June 2010, 130 consecutive patients received the HeartMate II LVAD. Of these, 102 were bridge-to-transplant (BTT), 17 destination therapy, and 11 exchanges for failed HeartMate XVE. This study focuses on the 102 BTT patients. The HeartMate II was approved by the US Food and Drug Administration (FDA) as BTT in April 2008 and 64 patients received this device as BTT since that date. We review our experience with the device as BTT and report on patient survival and adverse events as well as the impact of FDA approval on outcomes. Results: Overall, mean age was 52.6 ± 12.8 years; 26 (25.5%) were female. Disease etiology was ischemic in 58, nonischemic in 36, and other in 8. Overall, 30-day, 6-month, and 1-year survival for the BTT patients was 95.1%, 83.5%, and 78.8%, respectively. The 6-month survival in 38 patients in the clinical trial (pre-FDA) was 88.8% and was not statistically significant compared with the 76.2% 6-month survival in the 64 patients in the post-FDA approval period (p value = 0.1). Major adverse events among the 102 BTT patients included right ventricular failure in 5 (4.9%), LVAD driveline infections in 25 (24.5%), neurologic events in 10 (9.8%), and gastrointestinal bleeding in 18 (17.6%) patients. In addition, 1 patient (0.98%) had pump thrombus requiring device replacement. Conclusions: Despite significant morbidity, use of the HeartMate II LVAD as BTT provides excellent hemodynamic support and is associated with excellent survival and low mortality. In addition, there needs to be improvement and focused strategies in the areas of gastrointestinal bleeding, driveline infections, and adverse neurologic events for these devices to be able to provide a real long-term alternative to heart transplantation. [ABSTRACT FROM AUTHOR]

Objective: Pulsatile left ventricular assist devices have been shown to effectively reduce pulmonary hypertension in patients with end-stage heart failure. However, it remains to be seen whether newer continuous-flow left ventricular assist devices have a similar effect on pulmonary hypertension. The objective of this study was to determine whether the HeartMate II (Thoratec Corp, Pleasanton, Calif), a continuous-flow left ventricular assist device, is effective in improving pulmonary hemodynamics in the period after left ventricular assist device support and posttransplant. Methods: Fifty patients with end-stage heart failure underwent HeartMate II left ventricular assist device placement as a bridge to transplant. We evaluated their pulmonary hemodynamics with right-sided heart catheterization at baseline, after left ventricular assist device placement, and after heart transplant. Results: The mean age of patients was 53.7 ± 13.5 years. Ischemic etiology was present in 60% of the patients. After left ventricular assist device placement (mean duration, 135 ± 60 days), mean systolic and diastolic pulmonary artery pressures decreased significantly from a baseline of 55.2 ± 13.4 mm Hg and 27.3 ± 6.8 mm Hg, respectively, to 35.9 ± 10.8 mm Hg and 15.8 ± 6.5 mm Hg, respectively (P < .001). Similarly, mean pulmonary vascular resistance decreased significantly from a baseline of 3.6 ± 1.9 Woods units to 2.1 ± 0.8 Woods units (P < .001). Posttransplant pulmonary hemodynamics also remained within normal limits, even in patients with previously severe pulmonary hypertension. Conclusion: Continuous-flow left ventricular assist devices effectively improve pulmonary hemodynamics associated with end-stage heart failure. Moreover, pulmonary hemodynamics remain within normal limits in the posttransplant period, even in patients with severe pulmonary hypertension. Therefore, adequate left ventricular decompression achieved with newer left ventricular assist devices can reverse significant pulmonary hypertension in patients with end-stage heart failure, making them eligible for cardiac transplantation. [Copyright &y& Elsevier]

Objective: Thromboembolic events can occur in up to 20% of patients with a left ventricular assist device. The aggressive use of anticoagulation with newer continuous-flow devices has potentially increased the risk of postoperative bleeding. The predecessor of the HeartMate II left ventricular assist device, the HeartMate XVE (Thoratec Corp, Pleasanton, Calif), was associated with an extremely low thromboembolic risk, even without anticoagulation, because of its unique textured surfaces. Even though several areas of the HeartMate II are textured, a protocol was adopted for this new axial flow pump requiring long-term anticoagulation with warfarin. In our study, we investigated whether the HeartMate II left ventricular assist device is associated with a similarly low thromboembolic risk as the HeartMate XVE. Methods: At our institution, 45 patients (mean age, 57.24 ± 14.2 years) underwent implantation of the HeartMate II; 30 underwent bridge-to-transplantation therapy, 7 underwent destination therapy, and 8 underwent left ventricular assist device exchange for a failed XVE left ventricular assist device. Total duration of HeartMate II support was 352.13 patient-months (mean duration, 7.2 ± 5.2 months). All 45 patients were treated postoperatively with warfarin and aspirin. We recorded use of these 2 medications and monthly international normalized ratios. Prospectively, we also monitored patients for any clinical thromboembolic events and for pump thrombus. Results: Of our 45 study patients, 41 had a mean international normalized ratio of less than 2.0; of those 41 patients, 21 had a mean international normalized ratio of less than 1.6. Because of recurrent gastrointestinal bleeding episodes, 7 patients discontinued warfarin for a total duration of 39.1 patient-months. During the entire period of HeartMate II support, we noted 1 thromboembolic event. In addition, another patient had a suspected left ventricular assist device pump thrombus that resolved with a high-intensity heparin anticoagulation protocol (international normalized ratio, 1.3). Conclusions: Our preliminary single-center analysis suggests that the HeartMate II is associated with an extremely low thromboembolic risk and with less stringent requirements for anticoagulation. Selected patients at high risk for bleeding can be safely followed with either no or extremely low anticoagulation requirements for prolonged periods. [Copyright &y& Elsevier]

Background: Pulsatile left ventricular assist devices (LVADs) are effective as bridge-to-transplant therapy, but they are limited by their large size and lack of durability. Smaller, more durable, continuous flow devices such as the HeartMate II LVAD are increasingly being used. The aim of this study is to report our single-center experience with this device as bridge-to-transplant therapy. Methods: Overall, 47 patients received HeartMate II LVADs at our center from June 2005 to July 2007; 32 as bridge to transplant, 7 as destination therapy, and 8 as exchange therapy for a failed HeartMate XVE. We reviewed our experience with the device as bridge-to-transplant therapy and report on patient survival and adverse events. Results: The mean age of the bridge-to-transplant patients was 50.75 ± 13.78 years; 10 (31.3%) were female. The cause of the underlying disease was ischemic in 18 patients (56.3%), idiopathic in 11 (34.4%), myocarditis in 1 (3.1%), postpartum cardiomyopathy in 1 (3.1%), and congenital heart disease in 1 (3.1%). The mean duration of HeartMate II support was 193.2 ± 139.9 days. At 30 days after HeartMate II placement, the patient survival was 96.9% by Kaplan-Meier analysis; at 6 months (alive or transplanted), 86.9%. Major adverse events included bleeding requiring reexploration in 5 patients (15.6%), right ventricular failure requiring right ventricular assist device support in 2 (6.3%), LVAD-related infections in 4 (12.5%), neurologic or thromboembolic events in 2 (6.3%), and gastrointestinal bleeding in 5 (15.6%). We noted one serious device malfunction (3.1%) resulting in the patient''s death; in addition, 2 patients experienced pump thrombosis (6.3%). Conclusions: Despite morbidity, use of the HeartMate II LVAD as bridge-to-transplant therapy is associated with excellent survival and low mortality rates. We found a marked decrease in morbidity related to right ventricular failure, to device-related infections, and to thromboembolic events. However, the requirements for anticoagulation therapy may be associated with increased mediastinal and gastrointestinal bleeding. Strategies to optimize anticoagulation therapy may further improve results for these critically ill patients. [Copyright &y& Elsevier]

Objective: Patients with refractory acute cardiogenic shock and multisystem organ failure have a poor outcome with implantation of permanent ventricular assist devices. We review our experience with the use of the CentriMag (Levitronix LLC, Waltham, Mass) circulatory support system in such patients whose neurologic status was uncertain. Methods: From January 2004 to June 2006, 30 patients underwent CentriMag circulatory support system placement at the University of Minnesota. Of these patients, 12 were transferred from an outside hospital with refractory acute cardiogenic shock requiring biventricular support; they are the focus of this study. Results: Of our 12 study patients, 8 underwent successful bridging to the HeartMate XVE (Thoratec Corp, Pleasanton, Calif) ventricular assist device after biventricular support (mean support time of 9.4 days, range: 5–22 days). Another 2 patients underwent successful explantation (after 8 and 9 days); the remaining 2 patients died (after 4 days). Thus, the survival on CentriMag support, to either bridge or recovery, was 83% (10/12). Of the 8 patients who subsequently underwent HeartMate implantation, 5 also underwent a heart transplant within 6.9 months (range, 4.5-10 months), another 2 are still awaiting a transplant, and 1 died of sepsis and right ventricular failure 3 days after HeartMate implantation. Thus, for our 12 study patients, long-term survival was 75% at 1 month and 62.5% at 1 year. Conclusions: Our aggressive strategy in this group of patients involved early operative intervention and implantation of biventricular support. By using this strategy, we avoided the urgent placement of expensive long-term ventricular assist devices in hemodynamically unstable patients with multisystem organ failure whose neurologic status was uncertain until end-organ recovery and excellent hemodynamic stability were achieved with the relatively inexpensive short-term CentriMag circulatory support system. The excellent midterm outcomes in this group of patients whose original prognosis was poor justify this therapeutic strategy. [Copyright &y& Elsevier]

Abstract: Papillary fibroelastomas are benign cardiac tumors with high embolic potential typically found on the valvular surfaces of the heart. Nonvalvular papillary fibroelastomas are exceedingly rare. We report the case of a 66-year-old Caucasian male with acute bilateral basal ganglia infarctions found to have a mass adherent to the left ventricular septum by transesophageal echocardiography. The mass was identified as a rare nonvalvular cardiac papillary fibroelastoma based on echogenicity, pedunculated nature, and typical motion. Tissue characterization by cardiac magnetic resonance imaging demonstrated homogeneously hypo-intense signal on T2 weighted imaging and signal hyperintensity after administration of gadolinium contrast, confirming the fibroelastic nature of the mass. Surgical excision was performed via ventriculotomy and histopathologic examination was pathognomonic of a papillary fibroelastoma. We conclude that transesophageal echocardiography provides high diagnostic certainty in patients with cardiac papillary fibroelastomas and can reliably identify atypical locations of these tumors on nonvalvular surfaces. A multimodality imaging approach is not necessarily indicated in all patients with this condition. [Copyright &y& Elsevier]

To quantify the change in heart failure (HF) hospitalizations observed in the early phase of the COVID-19 pandemic across a large, multi-center health care system. MHealth Fairview encompasses four hospitals (one academic, three community-based) in the Minneapolis, Minnesota metro area. To compare HF hospitalization trends, two inpatient samples were created using HF discharges in the following time periods: pre COVID-19 (February 28, 2019-February 28, 2020) and post COVID-19 (April 1, 2020- May 15, 2020). March 2020 was excluded as this represented a transition point of the pandemic in the United States. Average number of discharges per day as well as demographics, diagnosis related group (DRG) codes, and inpatient mortality was then compared between the two inpatient HF samples. The pre COVID-19 group had 2,601 patients with an average of 7.1 (+/-3) discharges per day. The post COVID-19 group had 210 patients with an average of 4.7 (+/-1.7) discharges per day, which represented a 34% reduction in HF discharges (p <0.001). No statistically significant differences were observed between the pre and post COVID-19 inpatient samples with respect to age (76 vs. 75 years, p = 0.25), gender (46% vs. 48% male, p = 0.7), and DRG codes (DRG 291: 78% vs. 85% p = 0.15). Inpatient HF mortality pre and post COVID-19 was not significantly different (3% vs. 2.9%, p = 0.99). HF hospitalizations have decreased significantly during the early phase of the COVID-19 pandemic in this multi-center health care system, however the make-up of hospitalized patients remains similar. There is an urgent need to provide continued access to safe hospital care during the pandemic and to inform HF patients that inpatient care remains available. [ABSTRACT FROM AUTHOR]

The HeartMate 3 (HM3) left ventricular assist device (LVAD) has a low reported rate of pump thrombosis. In this case series, we report two HM3 LVAD recipients who developed acute pump thrombosis in the early post-operative period. A 69 M with ischemic cardiomyopathy who underwent HM 3 implant as destination therapy (DT). Apical calcium was noted intra-operatively and was removed at the time of surgery. On post-operative day 3, the patient developed low flows alarms, high powers, and increased arterial line pulsatility. Lactate dehydrogenase (LDH) was within normal limits and heparin was therapeutic. Pump interrogation demonstrated rising pump temperature (70°C) with intermittent pump stops. The decision was made to return to the operating room (OR) and during this time the patient developed hypotension and lactic acidosis. In the OR fresh thrombus of the inflow, pump and outflow graft was encountered. The pump was exchanged to a new HM3 and the patient had full recovery with no further thrombotic events. A 58-year-old woman with Adriamycin associated cardiomyopathy underwent DT HM3 implantation with tricuspid valve annuloplasty. The LV cavity size decreased from 5.9 cm pre- operatively to 4.0 cm post-operatively, causing septal contact with the inflow cannula and intermittent ventricular tachycardia. On post-operative day 3 the patient developed low flow alarms, followed by elevated pump flows and powers and return of arterial line pulsatility. LVAD interrogation demonstrated a high pump temperature (75 °C) with intermittent pump stops. Similar to the first patient, the second patient had a normal LDH, was therapeutic on a heparin drip, and developed hemodynamic instability. The same findings (inflow, outflow, and intra pump thrombus) were present at in the OR. This second patient's pump was re-positioned reduce septal contact at the time of exchange. Here we report 2 cases of acute HM3 pump thrombosis shortly after LVAD implantation. Full investigation into these events internally and with the manufacturer did not reveal pump malfunction. The first event was felt to be caused by ingestion of calcified material from the left ventricle leading to rotor misplacement and subsequent thrombus formation. The second case was thought to be triggered by sustained low flow from the septal contact with subsequent thrombus formation. In each case, the patients developed high powers, return arterial line pulsatility, and dangerously high internal pump temperatures. The purpose of this case series is to help the community develop pattern recognition in order to be able to quickly diagnose this rare but serious event. [ABSTRACT FROM AUTHOR]