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Infection is a serious adverse event limiting left ventricular assist device (LVAD) therapy in advanced heart failure patients, but a reliable means to identify patients at increased risk of infection is still lacking. We hypothesized that preoperative elevated levels of plasma Oncostatin M (OSM), a cytokine marker of leukocyte activation and inflammation, would be predictive of subsequent infection. We measured plasma OSM in 41 LVAD patients one day before LVAD implantation and postoperatively over two months. Preoperative plasma OSM levels were normal in 27 patients (group A, 4.9 ± 3.2 pg/ml) but elevated in 14 patients (group B, 1649.0 ± 458.9 pg/ml) ( p = 0.003). Early postoperative levels rose in both groups and declined rapidly in group A, with group B declining slowly over two months. Significantly more infections developed in group B than group A patients over two months postimplantation ( p = 0.004). No other routine clinical assessment or laboratory testing afforded this differentiation. These findings suggest that preoperative plasma OSM levels may assist in identifying patients at increased risk of infections after LVAD implantation. more...

Background With the limited number of available suitable donor hearts resulting in plateaued numbers of heart transplantations, short- and long-term mechanical circulatory support devices, including the implantation of total artificial hearts (TAHs) are modalities that are increasingly being used as treatment options for patients with end-stage heart failure. The superior vena cava syndrome has been described in this context in various disease processes. We report successful venoplasty for superior vena cava syndrome in a patient with a TAH. Case presentation A 65-year-old man with a history of nonischemic cardiomyopathy had received a left ventricular assist device, and then 2 years later, underwent orthotopic heart transplantation using the bicaval anastomosis technique. The postprocedural course was complicated by primary graft failure, resulting in the need for implantation of a TAH. About 5 months after TAH implantation, he started to develop complications such as volume retention, swelling of the upper extremities, and was diagnosed to have a superior vena cava syndrome. The patient underwent a successful venoplasty of his superior vena cava by interventional radiology with resolution of upper body edema, normalization of renal, and liver function. Conclusion Potential fatal complications caused by catheter or wire entrapment in the right-sided mechanical valve of a TAH have been reported. We describe a safe method for the treatment of superior vena cava syndrome in patients with TAH. more...

The severe acute respiratory syndrome-CoV-2 is an emerging viral pathogen responsible for the global coronavirus disease 2019 pandemic resulting in significant human morbidity and mortality. Based on preliminary clinical reports, hypoxic respiratory failure complicated by acute respiratory distress syndrome is the leading cause of death. Further, septic shock, late-onset cardiac dysfunction, and multiorgan system failure are also described as contributors to overall mortality. Although extracorporeal membrane oxygenation and other modalities of mechanical cardiopulmonary support are increasingly being utilized in the treatment of respiratory and circulatory failure refractory to conventional management, their role and efficacy as support modalities in the present pandemic are unclear. We review the rapidly changing epidemiology, pathophysiology, emerging therapy, and clinical outcomes of coronavirus disease 2019; and based on these data and previous experience with artificial cardiopulmonary support strategies, particularly in the setting of infectious diseases, provide consensus recommendations from American Society for Artificial Internal Organs. Of note, this is a living document, which will be updated periodically, as additional information and understanding emerges. more...

Extracorporeal membrane oxygenation has evolved, from a therapy that was selectively applied in the pediatric population in tertiary centers, to more widespread use in diverse forms of cardiopulmonary failure in all ages. We provide a practical review for cardiovascular clinicians on the application of veno-arterial extracorporeal membrane oxygenation in adult patients with cardiogenic shock, including epidemiology of cardiogenic shock, indications, contraindications, and the extracorporeal membrane oxygenation circuit. We also summarize cannulation techniques, practical management and troubleshooting, prognosis, and weaning and exit strategies, with attention to end of life and ethical considerations. more...

Venoarterial extracorporeal membrane oxygenation (ECMO) is a rescue therapy that can stabilize patients with hemodynamic compromise, with or without respiratory failure, for days or weeks. In cardiology, the main indications for ECMO include cardiac arrest, cardiogenic shock, post-cardiotomy shock, refractory ventricular tachycardia, and acute management of complications of invasive procedures. The fundamental premise underlying ECMO is that it is a bridge—to recovery, to a more durable bridge, to definitive treatment, or to decision. As a very resource- and effort-intensive intervention, ECMO should not be used on unsalvageable patients. As the use of this technology continues to evolve rapidly, it is important to understand the indications and contraindications; the logistics of ECMO initiation, management, and weaning; the general infrastructure of the program (including the challenges associated with transferring patients supported by ECMO); and ethical considerations, areas of uncertainty, and future directions. more...

Background: Veno-arterial extracorporeal membrane oxygenation (VA-ECMO) has been shown to be a viable and effective treatment for patients suffering from refractory cardiogenic shock (rCS), which is associated with high mortality rates. Although ECMO therapy used as short-term mechanical circulatory support (MCS) has shown tremendous growth in its application over the past decade, the complication and mortality rates remain high. This retrospective study analyzes complications associated with VA-ECMO support, evaluates the use of defined protocols at a single center, and examines factors that may contribute to patient complication and mortalit Methods: This retrospective analysis included 184 patients who were supported with ECMO from September 2014 through March 2018 at Integris Baptist Medical Center (IBMC). Descriptive statistics were generated to analyze baseline characteristics, demographics, complications, and outcomes. Results: Acute myocardial infarct (AMI) was the primary etiology of this cohort (N=40; 22%). The mean age was 55±15 (median 56, range 15–84) years. All patients were inotrope and/or vasopressor dependent prior to ECMO initiation. Mean time on ECMO support was 7.8±7.9 days with median time of 6 days. Total patient days on support were 1,430. Most ECMO cannulations, 97 (52%) were performed within Integris Baptist Medical Center, with 48% done outside the hospital; 38% were performed outside of the hospital by the IBMC ECMO team, and 10.5% were performed by an outside team. Bleeding was noted to be the most common VA ECMO complication [N=41; 22.3%; 0.028 events per patient day (EPPD)]. Conclusions: A dedicated 24/7 ECMO service using a multidisciplinary team (MDT) and defined protocols in a single center is able to effectively reduce complications due to VA-ECMO support in the sickest of the sick VA-ECMO patients. more...

A 71-year-old woman was admitted with acute hypoxic and hypercapnic respiratory failure and cardiogenic shock, secondary to acute on chronic biventricular systolic and diastolic congestive heart failure and severe aortic and mitral valve stenosis. She further presented with pulmonary hypertension and moderate-to-severe tricuspid regurgitation requiring high and increasing doses of vasopressors. The patient was percutaneously cannulated for venoarterial extracorporeal membrane oxygenation (VA-ECMO) and stabilized on ECMO, with a urine output of 17.3 L within the following 8 days. Balloon valvuloplasty and/or transcatheter aortic valve replacement were discussed but ruled out by the multidisciplinary team considering the mitral valve could not be fully addressed. Though lung function was not fully optimized, a window of opportunity was identified and used for double valve replacement on day 8 of VA-ECMO support. After a 24-hour vasoplegic period, the patient was extubated to continuous positive airway pressure and further transitioned to nasal cannula, following which she recovered well. more...

Purpose Extra corporeal membrane oxygenation (ECMO) indications and usage has remarkably progressed over the past decade. While the newer technology has improved durability compared to earlier generations, increased frequency in some complications has been seen, including gastrointestinal bleeding (GIB). We discuss the incidence and outcomes of GIB in patients receiving ECMO. Methods From September 2014 to September 2019, 468 patients required ECMO support for different indications (VA: 302, VV: 133, Combined: 33). We retrospectively reviewed the medical records and identified 48 (10.3%) patients diagnosed with GIB after being placed on ECMO. Their pre-cannulation characteristics and outcomes were then compared to the remaining patients (no GIB group). Fisher's exact test was used to test significance in categorical variables, and t-test for continuous variables. Results A total of 48 patients (mean age 59±14, male 35) were diagnosed with GIB post ECMO, of those 31 patients (65%) had upper GIB, 9 (19%) had lower GIB and 3 (6%) had combined. In 5 patients (10%) bleeding was unspecified. The mean time from ECMO initiation to the presentation of the event was 11 days (±11) and ranged from same day of cannulation to up to 60 days. Thirty-one patients (65%) were in the VA ECMO group, and 8 (17%) on VV ECMO. The remaining 9 (19%) patients were in the combined ECMO group. As seen in table 1, the mean duration of ECMO support and pre- cannulation SOFA score were significantly higher in the GIB group (p Conclusion Our data shows that GIB is a frequent complication (10.3%) in ECMO patients. However, there was no impact on the outcomes. Further studies are required to investigate and help better understand the etiology of GIB in those patients. more...

Purpose Reliable biomarkers to predict the outcome of Veno-Venous (V-V) ECMO therapy have not been identified. While lactic-acid (LA) levels are useful for predicting outcomes in Veno-Arterial (V-A) ECMO for patients with cardiogenic shock, they have not been reliable in V-V ECMO for patients with acute pulmonary failure. We hypothesize that markers of inflammation may be superior to markers of perfusion deficits in such patients. We evaluated Oncostatin M (OSM), a novel biomarker for inflammation (a member of the IL-6 family) for its potential to predict outcomes in patients with acute pulmonary failure requiring V-V ECMO. Methods Following informed consent, blood samples were collected pre-cannulation, then post-cannulation on days 1-3, and then every other day until decannulation from 29 V-V ECMO patients. Plasma OSM levels were measured by ELISA and compared with plasma LA levels in concurrently collected samples. Results Plasma OSM release, consistent with a highly activated inflammatory state, was detected in 18 of the 29 patients prior to V-V ECMO. Of these 18 patients, 7 expired and 11 eventually recovered. As shown in Fig. 1, the pre-decannulation OSM levels were significantly higher (Mann-Whitney U test: p=0.04) in patients who eventually expired than those who recovered (Median: 90.2% vs 49.4%). On the other hand, there was no significant difference in the LA levels (Mann-Whitney U test: p= 0.56) between those that eventually recovered and those who expired (Median: 82.7% vs 83.5%). Conclusion Plasma release of OSM, a novel biomarker for inflammation, was predictive of mortality in patients with acute respiratory failure supported by V-V ECMO whereas Lactic Acid levels were not. This important finding warrants further exploration. more...

Veno-arterial extracorporeal membrane oxygenation (VA-ECMO) provides mechanical circulatory support for patients with advanced cardiogenic shock, facilitating myocardial recovery and limiting multi-organ failure. In patients with severely limited left ventricular ejection, peripheral VA-ECMO can further increase left ventricular and left atrial pressures (LAP). Failure to decompress the left heart under these circumstances can result in pulmonary edema and upper body hypoxemia, that is, myocardial and cerebral ischemia. Atrial septostomy can decrease LAP in these situations. However, the effects of atrial septostomy on upper body oxygenation remain unknown. After IRB approval, we identified 9 out of 242 adult VA-ECMO patients between January 2011 and June 2016 who also underwent atrial septostomy for refractory pulmonary edema/upper body hypoxemia. We analyzed LAP/pulmonary capillary wedge pressure (PCWP), right atrial pressures (RAPs), Pa O2 /Fi O2 ratios (blood samples from right radial artery), intrathoracic volume status, and resolution of pulmonary edema before and up to 48 h after septostomy. There were no procedure-related complications. Thirty-day survival was 44%. LAP/PCWP decreased by approximately 40% immediately following septostomy and remained so for at least 24 h. Pa O2 /Fi O2 ratios significantly increased from 0.49 (0.38-2.12) before to 5.35 (3.01-7.69) immediately after septostomy and continued so for 24 h, 6.6 (4.49-10.93). Radiographic measurements also indicated a significant improvement in thoracic intravascular volume status after atrial septostomy. Atrial septostomy reduces LAP and improves upper body oxygenation and intrathoracic vascular volume status in patients developing severe refractory pulmonary edema while undergoing peripheral VA-ECMO. Atrial septostomy therefore appears safe and suitable to reduce the risk of upper body ischemia under these circumstances. more...

Purpose One major concern of utilizing veno-arterial (VA) ECMO in advanced cardiogenic shock (ACS) patients is its inability to completely unload the left ventricle (LV). However, the clinically significant degree of LV unloading required for recovery is not well described. We hypothesized that measuring hemodynamics during VA ECMO weaning would elucidate the impact of VA ECMO on LV unloading. Methods From January 2017 to September 2018, 67 ACS patients required VA ECMO support longer than 24 hours. Acute or chronic heart failure patients were excluded. A weaning protocol using hemodynamic measurements and echocardiography studies (ECHO) was applied in 42 patients who showed acceptable end organ recovery (mean age 58 ± 15; male 35). The etiology of ACS was acute myocardial infarction n=19, post-cardiotomy cardiogenic shock n=16, severe metabolic derangement n=3, and 1 case each of myocarditis, primary graft failure, traumatic and refractory ventricular fibrillation. The mean duration of support before weaning was 14 days (±10). Hemodynamics and ECHO measurements were obtained at full ECMO support (100%), then with support reduced to 75%, 50%, 25%, and off. Hemodynamic stability for more than 3 minutes was prerequisite to decrease support. Results Mean values of PCWP were significantly higher with ECMO support off than with full support (p Conclusion The results show the capability of VA ECMO to unload the LV to a clinically acceptable level. However, LV unloading should be carefully measured via complete hemodynamic assessment using SGC and ECHO. more...

Extracorporeal life support encompasses various techniques that support patients with severe cardiac and/or pulmonary failure. Extracorporeal membrane oxygenation (ECMO) is provided for stabilization of salvageable patients when death is imminent and other treatment options are not available. Advancements in ECMO technology have improved its safety and portability, which has led to a dramatic increase in its use. ECMO is an extension of cardiopulmonary bypass technique that has been routinely used in cardiac surgery. Today, ECMO is applied in multiple different scenarios, but more clinical research is needed to establish practice guidelines. more...

Peripheral veno-arterial extracorporeal membrane oxygenation (pVA-ECMO) has gained increasing value in the management of patients with critical cardiogenic shock (cCS), allowing time for myocardial recovery. Failure of myocardial recovery has life-altering consequences: transition to durable mechanical circulatory support (dMCS), urgent heart transplantation, or withdrawal of support. Clinical factors controlling myocardial recovery under these circumstances remain largely unknown. Using a retrospective cohort, we developed a model for early prediction of transition to dMCS in patients undergoing pVA-ECMO for cCS. To promote myocardial recovery, our clinical management centered around left ventricular pressure unloading, that is, targeting pulmonary capillary wedge pressures (PCWP) ≤18 mm Hg. We collected demographic data, laboratory findings, inotrope use, and two-dimensional transthoracic echocardiography measurements, all limited to the first 72h of pVA-ECMO (D1-3). Out of 70 patients who were alive after pVA-ECMO, 27 patients underwent implantation of dMCS. There was no significant difference in survival to hospital discharge between patients with or without transition to dMCS. Ejection fractionD1-3 (per 10% increase, OR 0.37 [0.17-0.79]) and amount of inotropic supportD1-3 (OR 4.77 [1.6-14.18]) but neither myocardial wall tension nor PCWP emerged as significant predictors of transition to dMCS. Optimism-corrected c-index (0.90 [0.89-0.90]) revealed an excellent discriminative ability of our model. In summary, our model for early prediction of transition to dMCS in patients with cCS undergoing pVA-ECMO identifies indicators of inotropic state as relevant factors. Absence of markers for myocardial oxygen consumption or left ventricular pressure loading allows us to hypothesize sufficient cardiac unloading in our cohort with PCWP-targeted management. more...

Although survival and quality of life have improved in patients with advanced heart failure (HF) after implantation of left ventricular assist devices (LVADs), they still pose risks of hemocompatibility-related complications, including thrombosis and bleeding. Development of biomarkers predictive of these LVAD-associated complications could guide decision making for both clinicians and patients. Recently, we showed higher plasma TGF-β1 levels within one-week after implantation with a miniaturized mechanical-bearing axial-flow pump HeartMate II (HM-II), and reasoned that platelet activation by the rotor may have caused the release of TGF-β1 in plasma in HF patients (Mancini et al. Transl. Res. 2018; 192:15-29). Recent clinical trials with the newest LVAD, the Heartmate 3 (HM-3), which uses a fully magnetically-levitated pump, showed superior clinical outcomes, including significantly reduced incidences of pump thrombosis and stroke (Mehra et al. N Engl J Med. 2019; 380:1618-1627). In this study, we evaluated release of TGF-β1 in plasma following implantation of HM-II and HM-3 LVADs compared to either coronary artery bypass graft (CABG) surgery or extracorporeal membrane oxygenation (ECMO) therapy. We measured serial total TGF-β1 levels in 38 Stage-D HF patients (11 received HM-II and 27 received HM-3). As a control, we collected blood samples from 10 patients undergoing CABG surgery, and 10 patients receiving ECMO therapy following acute onset cardio-pulmonary failure. Blood samples were collected before and 4-8 hours after procedures, and thereafter daily for up to one week. Plasma was prepared by centrifuging blood at 12,000 rpm for 5 min at 4°C within 10 min of blood drawing, which reduces in vitro release of TGF-β1 from platelets and thus allows accurate measurement of plasma TGF-β1. Total TGF-β1 levels were measured after acidification and neutralization of samples using DUO-ELISA kit (R&D Systems). Baseline total plasma TGF-β1 levels were higher in HF patients before LVAD implantation than in healthy controls [4.7 ± 1.9 ng/mL in HF patients (n= 38); 3.3 ± 0.8 ng/mL in healthy controls (n= 6); p=0.006)]. Total TGF-β1 levels surged transiently to 14.6 ± 6.1 ng/mL within 4-8 hours after LVAD implantation [(p We conclude that LVAD implantation causes a transient surge in total plasma TGF-β1 within a few hours after the procedure, presumably due to platelet activation by LVAD, not the surgery itself, as CABG or circulating blood through ECMO did not cause the surge. The observation that a reduced initial surge and lower levels of TGF-β1 in HM-3 vs. HM-II recipients needs further investigation to determine whether these differences are due to LVAD-specific factors (different rotors causing variable shear effects) or to confounding differences in implantation procedures, such as, by-pass time, cardiac tissue injury, number of platelet transfusions, blood suction with catheters etc. or other unknown factors. Our data suggest that serial TGF-β1 measurements after LVAD implantation may serve as a surrogate biomarker for platelet activation in association with hemocompatibility-related adverse events (Uriel et al. Circ. 2017; 135:2003-2012). Disclosures No relevant conflicts of interest to declare. more...

Purpose Morbidity and mortality in postcardiotomy cardiogenic shock (PCCS) patients are still high. Recent data from the Society of Thoracic Surgeons (STS) shows an increased number of patients undergoing coronary artery bypass grafting (CABG) in low-volume facilities. To address this, we established the Oklahoma Shock Network to deliver advanced therapy to these patients. We envisioned that transferring these patients to and managing them in hub centers, where highly-trained staff and advanced facilities are available, could improve their outcomes and help low-volume facilities better manage this sick cohort of patients. Methods Oklahoma Shock Network is a hub-and-spoke model that was initiated in September 2014 to manage patients with advanced cardiogenic shock/advanced respiratory failure. As of September 2018, 194 patients were transferred to our facility, of which 50 with severe PCCS were included in this retrospective review. Results All 50 patients were placed on VA ECMO (mean age: 58 ±14; male: 41; mean duration of support: 10 days ± 8). Mean distance traveled was 56 miles ± 59, with a range of 1 to 190 miles. ECMO was initiated in the OR, secondary to difficult weaning from CPB in 28 patients. In 22 patients, ECMO support was initiated after surgery, with mean time from surgery to ECMO initiation of 4 days. Prior to ECMO support, 1 patient was on Impella, while 21 (42%) had intra-aortic balloon pumps. Twenty-four patients underwent CABG (48%). Sixteen patients had other procedures in addition to CABG. One patient underwent VSD repair. Two patients each of MV replacement, AV replacement, and pericardiectomy. Three patients required aortic root replacement. There were no transport-related complications noted. Bleeding and tamponade were the most common complication (14 patients; 28%) followed by pneumonia in 11 patients (22%). Continuous renal replacement therapy was performed in 24 patients (48%). Twenty-nine patients (58%) were successfully weaned, of whom 20 (40%) were discharged from the hospital. Two were bridged to durable MCS, of which 1 patient was discharged (LVAD) and 1 deceased (TAH). Support was withdrawn in 17 patients (34%). Two patients required transition to Bi-VAD, but both died. Conclusion Our data demonstrates the safety of transferring early PCCS patients. The exceptional results justify expansion of the hub-and-spoke model to improve outcomes in PCCS patients. more...

Purpose There is limited data in the literature defining criteria for bridging advanced cardiogenic shock (ACS) patients supported by veno-arterial (VA) ECMO to durable Mechanical Circulatory Support (MCS). We evaluated our screening process on outcomes for all patients at our center bridged from VA ECMO to durable MCS. Methods From September 2014 to October 2018, 153 patients received VA ECMO for treatment of ACS greater than 24 hours. Care was withdrawn from 64 (42%) patients, 68 (44%) were successfully weaned from VA ECMO, 4 (3%) were bridged to extracorporeal biventricular assist device, and 14 (9%) were bridged to durable MCS, which were included in this retrospective analysis. All 14 patients accepted for durable support implantation underwent a multidisciplinary screening process. Criteria for candidacy included 1) acceptable end organ function, 2) extubation, 3) negative infection surveillance, and 4) neurologically intact. To compare clinical status pre VA ECMO and pre MCS, end organ function was assessed by Sequential Organ Failure Assessment (SOFA) score, lactic acid, renal, and hepatic markers. Outcomes assessed included survival and post durable MCS implant hospital length of stay (HLOS). Results As of October 2018, 11 of the 14 patients bridged to durable MCS are still alive (79%). Mean duration of support on VA ECMO before transition was 11 days ± 5 (4-22), and a mean of 343 days ± 312 (28-1041) on durable MCS. The mean post MCS HLOS was 29 days ± 20 (9-90). Of the 14 patients, 11 were transitioned to LVAD. One patient was explanted due to cardiac recovery, 1 received a heart transplant, 1 deceased, and 8 are still on LVAD support. In 2 patients, temporary RVAD support was required post LVAD. Three of the 14 were bridged to Total Artificial Heart, of which 2 have died. Conclusion Applying a thorough screening process to INTERMACS level 1 patients bridged with VA ECMO to durable MCS is a highly successful strategy and yields excellent long-term survival. Our screening process might be a useful guide to bridge select VA ECMO patients to cardiac transplantation. more...

Purpose Use of left ventricular assist device (LVAD) therapy is proven to be effective for the treatment of advanced heart failure. Heart transplant is not an option for patients with advanced age, frequently defined as age 70 or greater. The purpose of this study was to compare the survival rate post LVAD implantation for between patients who were less than 70 years or 70 years or older. Methods A retrospective review of patients implanted with an LVAD between March 2008 and February 2019 was conducted. 413 patients who received a continuous flow LVAD were included in the study. Patients were stratified by ≥70 years of age (n= 60) and Results Table 1 contains baseline demographics and survival. There was no statistically significant survival difference between the two groups. Survival in the 18-69 group vs the ≥70 group at 6 months was 87.8% vs 83.3% (p 0.302). 1 year survival was 81.6% and 83.3% (p 0.793), and 2 year survival was 70.3% and 71.7% (p 0.629), respectively. Figure 1 shows the Kaplan-Meier curves for each group. Conclusion LVAD recipients who were ≥70 years of age did not experience increased mortality compared to LVAD recipients who were 18-69 years of age. Patients should not be declined for LVAD therapy based on chronological age alone. more...

Purpose Right ventricular (RV) failure is associated with poor outcomes after left ventricular assist device (LVAD) placement. This can be treated with a temporary right ventricular assist device (RVAD), which ideally should be placed before the development of multisystem organ failure. The purpose of this study was to determine if there is any outcome difference in patients who underwent early or concurrent RVAD as compared to delayed RVAD implantation. Methods Via retrospective chart review, 32 patients who received temporary RVAD (30 CentriMag and 2 Protek Duo) were identified between 1/2013 and 7/2018. Subjects were divided into two groups as concurrent RVAD placement (defined as RVAD at the time of LVAD implantation) versus delayed RVAD placement (defined as an RVAD placed at any time after leaving the operating room for the LVAD implant). Survival, ICU and total length of stay (LOS), and total number of days on RVAD were compared utilizing Chi-square and two tailed t-test. Results Patients in the concurrent RVAD group had higher preoperative central venous pressure (p = 0.037). Survival rate at three months (χ² = 6.647, p 0.010) and one year (χ² = 3.983, p 0.046) was statistically significantly better among patients who received concurrent LVAD. ICU LOS, total hospital LOS, and number of days on RVAD were not statistically significant between the two groups. Conclusion Concurrent placement of a temporary RVAD for patients with RV failure at the time of LVAD implantation improves short- and long-term survival post LVAD implantation as compared to a delayed RVAD approach. more...

Purpose Strokes and infection are two potential complications in patients with left ventricular assist devices (LVADs). The combination of infection and stroke is particularly concerning for LVAD recipients and may be interrelated. We evaluated the impact of concomitant bacteremia in LVAD patients who suffered a stroke. Methods All patients implanted with a continuous flow LVAD at our center from 2009 to 2019 who experienced a stroke post LVAD implantation were included. Stroke was defined by clinical signs of stroke and confirmed by neuroimaging. We then assessed the number of hemorrhagic (HCVA) and ischemic (ICVA) strokes. All patients with bacteremia prior to stroke were included in the analysis. Kaplan Meier survival curves were used to evaluate survival. Results A total of 117 LVAD patients with strokes were included, of those 62 had ICVA (53%) and 55 had HCVA (47%). Forty-three of these patients (37.6%) had an episode of bacteremia prior to their stroke, of whom 14 were in the ICVA group and 29 in the HCVA group. Figure 1 demonstrates that patients with strokes and concomitant bacteremia carry significantly increased risk of mortality over two years (p=0.046) compared to patients with strokes without bacteremia. Of the observed deaths, 8 out of 14 (57%) in the ICVA group died, while 19 of the 29 (66%) in HCVA died within a 2 year period. Conclusion LVAD patients with bacteremia who have a stroke carry significantly worse 2 year survival when compared to those who do not have bacteremia at the time of their stroke. Patients with bacteremia and concomitant stroke may benefit from further investigation to create strategies to reduce the probability of subsequent mortality. more...

Purpose Peripheral veno-arterial extracorporeal membrane oxygenation (pVA-ECMO) has gained increasing value in the management of advanced cardiogenic shock. Unloading the left ventricle (LV) while reducing myocardial oxygen consumption (MVO2) are crucial for myocardial recovery during pVA-ECMO. To study the effects of a pulmonary capillary wedge pressure (PCWP)-directed protocol in patients on pVA-ECMO (goal: PCWP Methods Following IRB approval, we identified 99 patients with advanced cardiogenic shock undergoing pVA-ECMO and at least one formal transthoracic echocardiography study (TTE) during pVA-ECMO. We analyzed demographic data, routine laboratory data, hemodynamic parameters, and TTE results. We used PCWP measurements and calculations of LV systolic wall tension (LVSWT) to assess LV unloading and MVO2 during pVA-ECMO, respectively. Statistical analyses included Mann-Whitney-U test and logistic regression modeling. Data are given as median (interquartile range). Results Survival to hospital discharge was 60.6%. 27.3% of all patients required transition to dMCS to be weaned off pVA-ECMO. 10.1% of all patients developed refractory LV distention with pulmonary edema despite maximum medical treatment and required either atrial septostomy or additional mechanical support. Minimum PCWP readings during pVA-ECMO were 12.8 mmHg (11.0-14.4) in patients without and 10.0 mmHg (8.0-17.0) in patients with need for dMCS (p=0.236). Minimum LVSWT during pVA-ECMO were 2.7 × 105 dynes/cm (2.0-3.5) in patients without and 3.5 × 105 dynes/cm (3.1-4.0) in patients with need for dMCS (p=0.002). Adjusting for age and race in a logistic regression model revealed that only post-cardiotomy pVA-ECMO and LVSWT, but not minimum PCWP were independently associated with need for dMCS after pVA-ECMO. Conclusion We show that strict medical management can lead to LV unloading, i.e. minimum PCWP more...

The optimal timing of left ventricular assist device (LVAD) implantation in the management of advanced heart failure remains controversial. We hypothesize that in patients with cardiogenic shock, the severity of end-organ dysfunction as determined by the sequential organ failure assessment (SOFA) score is a determinant of outcomes after LVAD implantation. We determined the preoperative SOFA score and short- and long-term outcomes of 97 consecutive patients who received HeartMate II or HeartWare LVAD at our institution since January 2007. Kaplan-Meier analysis was used to compare long-term survival across SOFA score subgroups. The overall 30 day mortality was 10.1%, with no significant difference among SOFA score subgroups. Patients with scores ≥9 had significantly longer hospital stay (26 ± 6 vs. 18 ± 10 days, p = 0.03). One-year survival for SOFA scores 0-2, 3-5, 6-8, and ≥9 was 94%, 75%, 64%, and 29%, respectively. SOFA score was significantly lower in survivors at 6, 9, 12, 24, and 36 months. SOFA score did not predict adverse outcomes of bleeding, cerebrovascular events, infection, or pump exchange. These results show that preoperative SOFA score is a powerful predictor of outcomes after LVAD implantation. Long-term outcomes can be significantly improved by early intervention before emergence of end-organ dysfunction. more...

In several case reports and case series, extracorporeal membrane oxygenation during chest compression (CPR) has been shown to be a reasonable tool to improve outcome of patients under resuscitation. Although recommendations for extracorporeal cardiopulmonary resuscitation (ECPR) include younger patients with shockable rhythm and short previous CPR-time, it remains unclear if nonhighly selected patients have a similar outcome. Aim of this study was to determine outcome in our nonhighly selected patient population treated with ECPR and investigate possible predictors of survival. We made a retrospective single-center study of adults who underwent ECPR for in-hospital cardiac arrest between June 2008 and September 2016. Outcome and predictors of survival were identified. In this period of time, 59 patients underwent ECPR due to cardiac arrest. Fifteen patients (25.4%) survived discharge of which all had a good neurological outcome (cerebral performance category ≤ 2). Survival to discharge of patients with shockable rhythm (ventricular fibrillation or ventricular tachycardia) was 40.7%. Serum lactate ≥ 8, pulseless electrical activity (PEA) or asystole and male gender could be identified as predictors for low survival rate. Age, body mass index, renal replacement-dependent kidney injury had no significant influence on survival outcome. Mean CPR-time was 41.1 minutes (interquartile range, ±29.25 minutes). Extracorporeal membrane oxygenation seems to be a useful tool to improve the outcome of CPR also in nonhighly selected patients when compared with CPR alone and could be considered in patients with refractory cardiac arrest also after longer previous CPR-time. Serum lactate and heart rhythm should be taken into account for patient selection. more...

The impact of extracorporeal membrane oxygenation (ECMO) support on coronary blood flow and left ventricular unloading is still debated. This study aimed to further characterize the influence of ECMO on coronary artery blood flow and its ability to unload the left ventricle in a short-term model of acute cardiogenic shock. Seven anesthetized pigs were intubated and then underwent median sternotomy and cannulation for venoarterial (VA) ECMO. Flow in the left anterior descending (LAD) artery, left atrial pressure (LAP), left ventricular end-diastolic pressure (LVEDP), and mean arterial pressure (MAP) were measured before and after esmolol-induced cardiac dysfunction and after initiating VA-ECMO support. Induction of acute cardiogenic shock was associated with short-term increases in LAP from 8 ± 4 mm Hg to 18 ± 14 mm Hg (P = 0.9) and LVEDP from 5 ± 2 mm Hg to 13 ± 17 mm Hg (P = 0.9), and a decrease in MAP from 63 ± 16 mm Hg to 50 ± 24 mm Hg (P = 0.3). With VA-ECMO support, blood flow in the LAD increased from 28 ± 25 mL/min during acute unsupported cardiogenic shock to 67 ± 50 mL/min (P = 0.003), and LAP and LVEDP decreased to 8 + 5 mm Hg (P = 0.7) and 5 ± 3 mm Hg (P = 0.5), respectively. In this swine model of acute cardiogenic shock, VA-ECMO improved coronary blood flow and provided some degree of left ventricular unloading for the short duration of the study. more...

Purpose Gastrointestinal bleeding (GIB) is one of the most common complications following left ventricular assist device (LVAD) implantation. Correlation of right heart failure and GIB after LVAD has previously been demonstrated, however no predictive scores have been developed to identify those at risk. The purpose of this this study was to determine if pulmonary artery pulsatility index (PAPi) is a predictor of GIB post LVAD implantation. Methods We retrospectively reviewed electronic medical records of LVAD patients in our institution from 2015 to 2018. All patients with a clinically significant GIB were selected for analysis and compared to a random cohort of matched patients without GIB. A clinically significant GIB was defined as a drop in Hemoglobin >2 g/dL, clinical signs or symptoms of GIB and/or need for transfusion of packed red blood cells. PAPi score was calculated using pre-operative hemodynamics and comparisons between the two groups were completed using a Pearson correlation coefficient. Results A total of 110 LVAD patients were included, 53 were identified to have clinically significant GIB bleeding and were compared to 57 controls. The GIB cohort was found to be more likely to have a PAPi Conclusion PAPi has been shown to be a powerful predictor of right ventricular failure following LVAD implantation. Our study demonstrates that PAPi may also predict other clinically significant outcomes, specifically GIB. more...

Purpose Left Ventricular Assist Devices (LVADs) have successfully been established as a treatment for advanced heart failure. However, many areas of the country do not have direct availability to LVAD programs. Therefore, building patient care networks is essential to successful outcomes for patients living in rural areas. The goal of this study is to analyze the effect of distance from an LVAD implanting center on patient survival. Methods We retrospectively analyzed all patients at our center who received HeartMate II LVADs as both “bridge-to transplant” and “destination therapy” from 2008 to 2016, 185 patients were included. Patients were excluded if they: (1) received a transplant, (2) had their LVAD explanted, (3) were transferred to another hospital for care, or (4) failed to reach outpatient status. Patients were then divided into 3 groups based on distance (miles) from their home to the implanting center. Group 1: less than 29, Group 2: between 30 and 120, and Group 3: greater than 120 miles from our implanting center. We then compared survival outcomes at 3, 6, 12, 18, and 24 months on LVAD support. Logistic regression analysis was used to determine statistical significance, p valve Results See Table Conclusion Residential distance from implanting LVAD medical center did not have an adverse effect on the survival outcomes. This supports the notion that a well designed patient care network can provide effective care for patient living remotely from the implanting center. more...

Preexisting organ dysfunctions are known factors of death after placement of implantable mechanical circulatory support (MCS). Extracorporeal membrane oxygenation (ECMO) may able to stabilize organ function in patients with cardiogenic shock before MCS implantation. Between 2008 and 2012, 17 patients with cardiogenic shock were supported with ECMO before implantable MCS placement. Patient's end-organ functions were assessed by metabolic, cardiac, hepatic, renal, and respiratory parameters. Survival data after MCS implantations were analyzed for overall survival to discharge, complications, and breakpoint in days on ECMO to survival. Before MCS implantation, lactate, hepatic, and renal functions were improved and pulmonary edema was resolved. The interval between ECMO initiation and MCS placement was 12.1 ± 7.9 days. Overall survival rate to discharge after left ventricular assist device/total artificial heart placement was 76%. The survival of patients transitioned from ECMO to MCS within 14 days was 92% and was significantly better than the survival of patients from ECMO to MCS supported longer than 14 days, 25%, p < 0.05. ECMO support can immediately stabilize organ dysfunction in patients with cardiogenic shock. After improvement of organ function, MCS implantation should be done without delay, since the patients supported for longer than 14 days with ECMO had inferior survival compared to national data. more...

may also be beneficial in correcting misimpressions. It is important to present objective, statistical information in keeping with the patient’s clinical profile, although the power of such information to counter bias introduced by patient-to-patient encounters remains uncertain. A postsurgery ‘‘buddy system’’ between candidates and narrators is relatively free of bias concerns because the treatment decision was made previously and may facilitate postsurgery coping and adjustment. Our case and available evidence highlight the benefits and potential hazards of patient-to-patient encounters, hence our call for reflective, consistent practices. more...

Background: Significant advances in extracorporeal technology have led to the more widespread use of veno-arterial extracorporeal membrane oxygenation (VA ECMO) for cardiac failure. However, procedures for weaning from VA ECMO are not standar‐ dized. High death rate after successful weaning shows that many questions remain unresolved in this field. Objectives: In this review, we discuss data from the literature and propose a strategy to optimize the weaning process. Data synthesis and conclusions: It is especially important that the VA ECMO is not removed while the patient is still recovering from the condition that necessitated the use of VA ECMO implantation. Damaged organs need to recover before attempting weaning and the patient should be considered hemodynamically stable. The etiology of cardio-circulatory dysfunction must be compatible with myocardial recovery. Finally, weaning trials using echocardiographic and hemodynamic assessments are indispensable to assess the behavior of the ventricles and to determine whether the VA ECMO can be removed. more...

A growing population experiencing heart failure (100 000 patients/year), combined with a shortage of donor organs (less than 2200 hearts/year), has led to increased and expanded use of mechanical circulatory support (MCS) devices. MCS devices have successfully improved clinical outcomes, which are comparable with heart transplantation and result in better 1-year survival than optimal medical management therapies. The quality of perfusion provided during MCS therapy may play an important role in patient outcomes. Despite demonstrated physiologic benefits of pulsatile perfusion, continued use or development of pulsatile MCS devices has been widely abandoned in favor of continuous flow pumps owing to the large size and adverse risks events in the former class, which pose issues of thrombogenic surfaces, percutaneous lead infection, and durability. Next-generation MCS device development should ideally implement designs that offer the benefits of rotary pump technology while providing the physiologic benefits of pulsatile end-organ perfusion. more...

We recently had the opportunity to investigate the ventilatory effects of changing the rate of venous return to the heart (and thus pulmonary gas exchange) in a patient equipped with a venous-arterial oxygenated shunt (extracorporeal membrane oxygenation (ECMO) support). The presence of the ECMO support provided a condition wherein venous return to the right heart could be increased or decreased while maintaining total aortic blood flow and arterial blood pressure (ABP) constant. The patient, who had received a heart transplant 12 years ago, was admitted for acute cardiac failure related to graft rejection. The clinical symptomatology was that of right heart failure. We studied the patient on the 4th day of ECMO support, while she was breathing spontaneously. The blood flow diverted through the ECMO system represented 2/3 of the total aortic flow (4 l min(-1)). With these ECMO settings, the baseline level of ventilation was low (3.89+/-0.99 l min(-1)), but PET(CO2) was not elevated (37+/-2 mmHg). When Pa(CO2) in the blood coming from the ECMO was increased, no stimulatory effect on ventilation was observed. However, when the diversion of the venous return to the ECMO was stopped then restored, minute ventilation respectively increased then decreased by more than twofold with opposite changes in PET(CO2). These maneuvers were associated with large changes in the size of the right atrium and ventricle and of the left atrium. This observation suggests that the change in venous return affects breathing by encoding some of the consequences of the changes in cardiac preload. The possible sites of mediation are discussed. more...

The clinical manifestation and natural history of myocarditis range is variable from asymptomatic stages to intractable circulatory compromise and death. Supportive therapy is paramount in the treatment of this condition. The use of mechanical circulatory support as bridge-to-recovery or bridge-to-transplantation in cases of cardiovascular collapse is often the only therapeutic option for these patients. We report the case of an adolescent boy with toxic myocarditis, due to cannabis abuse, who was supported with a Thoratec left ventricular assist device (Thoratec Laboratories Corp, Pleasanton, CA) for 96 days before device removal. more...

To identify proteins involved in cardiac regeneration, a proteomics approach was applied. A total of 26 proteins, which displayed aberrant expression in mouse hearts infarcted through ligation of the left anterior descending coronary artery, were identified. These included the intermediate filament protein nestin, which was up-regulated in the infarct border zone. Corresponding changes were observed for its mRNA. Nestin mRNA was also up-regulated in hearts from 17 of 19 patients with end-stage heart failure, including 4 with acute myocardial infarction in comparison with 8 donor hearts. Immunofluorescence confocal laser scanning microscopy revealed that nestin is expressed, on the one hand, in small proportions of cardiomyocytes, endothelial cells, smooth muscle cells, neuronal cells, and fibroblasts. On the other hand, it was found to be coexpressed with the stem cell markers c-kit, Sca-1, Mdr-1, and Abcg2 in small interstitial cells. In infarcted hearts from chimeric mice transplanted with bone marrow from enhanced green fluorescent protein (EGFP) transgenic mice, less than 1% of nestin-positive cells coexpressed EGFP, although EGFP-positive cells were abundant in these. Consequently, enhanced expression of nestin in the injured myocardium might reflect spontaneous regenerative processes supposedly based on the differentiation of resident cardiac stem cells into diverse cardiac cell types. more...

Heart transplantation is currently the treatment of first choice in patients with end-stage refractory heart failure. But already the demand for donor organs cannot be met, and patients face long waiting times for transplantation. In the future waiting times will become even longer as life expectancy increases and the number of heart-failure patients requiring transplantation grows. Consequently, in view of the poor prognosis of the disease in its advanced stages, alternatives to heart transplantation are increasingly gaining importance. In recent years new innovative treatment methods and techniques have been developed which have already proved clinically successful in patients with end-stage heart failure, especially as bridging measures. Some of these techniques appear suitable for long-term use and could therefore serve as an alternative to heart transplantation in some patients. Interesting new avenues of research may even lead to cardiac cell replacement therapies in the future. These approaches are currently undergoing initial clinical trials. This report presents surgical and cardiologic treatments for end-stage heart failure that have already been clinically investigated as well as techniques that are still in the preclinical stage and discusses their potential as alternatives to heart transplantation. more...

Die MARS-Lebertherapie (Molecular Adsorbent Recirculating System) konnte zeigen, dass das Uberleben von Patienten mit einer akuten Dekompensation einer chronischen Lebererkrankung durch den Einsatz der Therapie verlangert wird. MARS ist eine extrakorporale Behandlung, bei der als Dialysat Humanalbumin verwendet wird und die so albumingebundene Substanzen aus dem Blut entfernen kann. Das Albumin wird uber in einem geschlossenen Kreislauf uber Aktivkohle- und Anionenadsorber geleitet und so fur eine kontinuierliche Behandlung gereinigt. Trotz der Fortschritte der Technologie und der modernen Intensivtherapie, ist die Uberlebensprognose von Patienten mit kardiogenem Schock schlecht. Die Mortalitatsrate betragt bis zu 80%, haufig bedingt durch anhaltendes Multiorganversagen. Um herauszufinden, ob diese Patienten mit hypoxischem Leberversagen nach Herzoperationen von MARS profitieren, wurde eine prospektive, kontrollierte, randomisierte Studie durchgefuhrt. Als primares Zielkriterium galt das Uberleben auf der Intensivstation. Im Zeitraum von 8/00 bis 6/02 wurden 40 Patienten in die Studie eingeschlossen; 20 in die MARSGruppe (M) und 20 in die Gruppe mit Standardtherapie (ST). Alle wiesen Bilirubinspiegel >8 mg/dl auf. Zwischen den beiden Gruppen zeigten sich bei Einschluss keine wesentlichen Unterschiede. Die M-Gruppe wurde an 3 aufeinander folgenden Tagen mit MARS behandelt. Wenn danach die Bilirubinspiegel >6 mg/dl waren, wurde MARS fortgesetzt. Die STGruppe erhielt intensivmedizinische Standardtherapie. ST-Patienten mit weiter ansteigendem Bilirubin >15 mg/dl erhielten aus ethischen Grunden spater MARS (SM Gruppe; n=13). In der M-Gruppe (n=20) gab es 8 Uberlebende (40%) auf der Intensivstation, in der Gruppe der Patienten, die niemals mit MARS (KM) behandelt wurden (n=7) nur einen Uberlebenden (14,3%) (p=0,438). Trotz der geringen Anzahl von Patienten in dieser Analyse, kann MARS empfohlen werden fur die Therapie von akutem hypoxischen Leberversagen, da die Therapie lebensverlangernd sein kann. Weitere Studien sind notig um diese Ergebnisse zu verifizieren. more...

BACKGROUND: Several risk factors for early mortality after intra-aortic balloon pump (IABP) implantation have been described. METHODS: We performed a retrospective analysis in 120 patients receiving peri- or postoperative IABP support. Univariate and multivariate analyses were carried out to assess variables potentially influencing 30-day mortality in order to develop a risk score for the prognosis of survival and for the decision on optimal patient-specific treatment. RESULTS: The 4 parameters (mean arterial pressure, adrenaline dose, central venous pressure, and blood lactate concentrations) at 6 hours of IABP use were independently related to 30-day mortality. They were used to develop a risk score (0 - 4 points). With this score, patients who scored 3 or 4 points had no probability of surviving, whereas patients with a score of zero had a probability of 84.4 %. A prospectively screened cohort of 145 patients confirmed the reliability of our risk score. CONCLUSIONS: Our data demonstrate that a score can predict 30-day mortality in patients with IABP implantation. Such a score can be useful to find out whether or not ECMO/VAD implantation is necessary. more...

Background Infection is the leading cause of death for left ventricular assist device (LVAD) patients with end-stage heart failure. Decreased infection may be possible with fully implantable LVADs such as the LionHeart, which lacks percutaneous conduits (PCs), a common source of device-related infection (DRI). This sub-study reports infections with the LionHeart and compares these results with historic data from the REMATCH trial, bridge to recovery (BTR) and bridge-to-transplantation (BTT) studies. Methods Twenty-three patients were implanted with the LionHeart LVAD and followed until death or heart transplant during a non-randomized, multicenter, European trial from October 1999 to April 2004. The nature and incidence of infection were analyzed and adjudicated to definitions similar to, or the same as, the REMATCH definitions. Results The combined number of implant days was 7,980, with a mean of 347 days (median 112, range 17 to 1,259 days). Survival at 1 year was 39%, with 2-year survival at 22%. Seventy-four percent of patients developed one or more infections, with 30% developing sepsis, and 35% developing pump-pocket infections (PSIs). No patients developed pump-housing or inflow- or outflow-tract infections (PI). For comparison, the prevalence rates of sepsis, PSI and PI in REMATCH were 51%, 35% and 19%, respectively. Conclusions The patients in the European LionHeart Clinical Utility Baseline Study (CUBS) trial had less sepsis and less overall DRI compared with the REMATCH LVAD group. Therefore, the fully implanted device may cause less infection than PC devices during destination therapy (DT). Although lower for DT, these rates are still higher than for some BTT experiences. Areas for future improvement include miniaturization of controller/battery components to reduce wound complications related to pocket size, and installation of more modern lithium-ion batteries to decrease the need for re-operations due to battery end-of-life. more...

Background Neurologic events such as thromboembolic and hemorrhagic strokes are common complications of mechanical circulatory support. We report the neurologic events observed in patients treated for end-stage heart failure with the implantable, pulsatile LionHeart left ventricular assist device (LVAD). This sub-study was part of the LionHeart European Clinical Utility Baseline Study (CUBS). Methods Twenty-three male patients were implanted with the LionHeart LVAD in a non-randomized, observational study. Neurologic events were classified into three categories: (1) transient ischemic attacks (TIAs); (2) strokes, including cerebrovascular accidents (CVAs) and intracranial bleeding (ICB); and (3) "other," including hypoperfusion, coma and brain death. Neurologic injuries were also categorized as transient/reversible or permanent/disabling. Results Thirteen of 23 patients (57%) had a total of 30 neurologic events. Eight patients (35%) had 18 TIAs. Eight patients (35%) also had a stroke, either CVA ( n = 5, 22%) or ICB ( n = 3, 13%), and 5 of these patients (22%) also had 12 TIAs. Three patients (13%) had 4 "other" neurologic events. Ten patients (43%) had transient/reversible neurologic deficits and 10 (43%) had permanent/disabling events. One patient (4%) had intracranial bleeding as a primary cause of death (anti-coagulation–related hemorrhage). The combined incidence of neurologic events was 1.37 events/patient-year. The incidences of transient and permanent events were 0.91 and 0.46 event/patient-year, respectively. Conclusions Neurologic events caused morbidity in the CUBS trial, with infrequent mortality. These results are similar to previous experiences with destination therapy and underscore the need for improvements in LVAD design, patient selection and patient management to reduce the incidence of neurologic events. more...

Extracorporeal membrane oxygenation (ECMO) is generally used as a last resort to provide cardiopulmonary support in patients whose advanced cardiac or respiratory failure does not respond to less invasive treatments. Lower-limb ischemia secondary to the large diameter of the arterial cannula is one of ECMO's major limitations: in patients who have small-caliber arteries, the cannulas can reduce native blood flow. The creation of a T-graft—a well-described technique to avoid limb ischemia—enables flow into the ECMO cannula without jeopardizing blood flow to the limb. However, leaving the graft exposed through an open groin wound can result in dislodgment, and it increases the risk of infection. We describe our modification of a conventional T-graft in an 18-year-old woman who had systolic heart failure, acute respiratory distress syndrome, and small-caliber femoral vessels. We tunneled a polytetrafluoroethylene graft inside a Dacron graft, then ran the combined graft through a subcutaneous tunnel similar to that created for a peripheral bypass. Thus, the graft was protected from environmental exposure and the risk of infection. Our technique seems safer and more secure than the original T-graft technique, and we recommend its consideration during ECMO cannulation. more...

Background— In heart failure (HF), ventricular myocardium expresses brain natriuretic peptide (BNP). Despite the association of elevated serum levels with poor prognosis, BNP release is considered beneficial because of its antihypertrophic, vasodilating, and diuretic properties. However, there is evidence that BNP-mediated signaling may adversely influence cardiac remodeling, with further impairment of calcium homeostasis. Methods and Results— We studied the effects of BNP on preload-dependent myocardial sarcoplasmic reticulum Ca 2+ ATPase (SERCA2a) expression. In rabbit isolated muscle strips stretched to high preload and shortening isotonically over 6 hours, the SERCA/glyceraldehyde phosphate dehydrogenase mRNA ratio was enhanced by 168% (n=8) compared with unloaded preparations (n=8; P P Conclusions— Our data indicate that preload stimulates SERCA expression. BNP antagonizes this mechanism via guanylyl cyclase-A, cGMP, and cGMP-dependent protein kinase. This novel action of BNP to uncouple preload-dependent SERCA expression may adversely affect contractility in patients with HF. more...

The Molecular Adsorbent Recirculating System (MARS) has been proven to prolong survival in patients with hepatorenal syndrome. MARS is a modified dialysis that uses an albumin containing dialysate, which is recirculated and perfused online through charcoal and anion exchanger columns. It allows the selective removal of albumin bound substances. Despite advances in medical therapy and technology, the prognosis of patients with cardiogenic shock remains poor. Mortality rates are as high as 80%, often because of persistent multiple organ failure. To determine whether patients with hypoxic liver failure after cardiogenic shock after cardiac surgery might benefit from MARS, we performed a prospective, randomized, controlled, single center study. The primary objective was to prove that MARS improves survival. This article is a report on the interim analysis of the first 27 patients included between August 2000 and December 2001; 14 patients were in the MARS group, and 13 patients were in the non-MARS group. All had bilirubin levels greater than 8 mg/ml. Both groups had a similar risk profile. The MARS group received MARS for 3 consecutive days-if bilirubin was still greater than 6 mg/dl afterward, MARS was continued. The non-MARS group received conventional therapy. We had seven survivors in the MARS group (50%) compared with four (32%; p = ns) in the non-MARS group . We conclude that despite the limited number of patients included in this analysis, MARS can be recommended for patients with acute, hypoxic liver failure because it might prolong survival. Further studies in similar patient cohorts are needed to verify our results. more...

OBJECTIVES Against the background of an increasing number of patients suffering from severe congestive heart failure, mechanical circulatory support becomes more and more important. The indications for this therapeutic option ranges from bridging to cardiac transplantation, the application of the most recent systems as an alternative to transplantation, as well as in cardiogenic shock following open-heart surgery, acute myocardial infarction of fulminant myocarditis. PATIENTS AND METHODS Between September 1987 and November 2002, 670 implantations of 11 different mechanical circulatory support systems were performed in 607 patients (125 women, 482 men, age 1 month - 82 years). 255 patients received the device as a bridge to recovery (BTR) of their native organ, 276 patients as a bridge to cardiac transplantation (BTT), 49 patients as an emergency measure in life-threatening cardiogenic shock (bridge-to-bridge, BTB), and 27 patients as an alternative to transplantation (ATT). RESULTS 38% of the BTR group, 56% of the BTT group, 34% of the BTB group and 27% of the ATT group underwent successful cardiac transplantation or could be discharged from hospital. Infections and thromboembolic events were the most frequent complications but decreased with increasing experience and sophistication of devices. Some systems offer the possibility of discharging patients home while on the device. In our cohort, 90 patients left the hospital on support for a mean duration of 204 days. Readmission rate after 200 days was 50% and was system-related in less than 6%. CONCLUSIONS In spite of a still considerable morbidity associated with the employment of mechanical circulatory support, the results are encouraging and justify the high economic burden. more...

Background Chronic heart failure is a multifactorial, progressive disease of many causes and is associated with complex ventricular remodeling. Deposition of extracellular matrix proteins and sarcomeric disarray of the myocytes occur in end-stage heart failure. Ventricular assist devices (VAD), implanted as bridge to transplantation, may reverse ventricular remodeling. Although successfully weaning patients from VAD support has been reported, it is not clear to what degree reversal of remodeling occurs in unloaded failing hearts. Because collagen deposition and ultrastructural disarray are hallmarks of myocardial remodeling, we analyzed the myocardial ultrastructure and collagen content of VAD-supported hearts before and after mechanical unloading. Methods We used amino acid analysis to measure collagen content (4-hydroxyproline content) in 24 transplant candidates receiving VAD support. We used transmission electron microscopy to examine the ultrastructure in 6 patients receiving VAD support. Results The 4-hydroxyproline content increased significantly at VAD implantation and was not altered by mechanical unloading. The ultrastructure showed signs of persisting cardiomyopathy. Conclusion Mechanical unloading does not alter the total collagen content of the supported, failing heart. Thus, structural reversal of the remodeling process associated with heart failure is not a general phenomenon in mechanically unloaded hearts. more...

Uberbruckungsmoglichkeiten. Lange Zeit standen fur die Uberbruckung bis zur Herztransplantation bei Kindern und Jugendlichen ausschlieslich die bei Erwachsenen etablierten Systeme zur Verfugung. Wir haben das Thoratec-System (Schlagvolumen 65 ml) bei 8 Kindern und Jugendlichen eingesetzt. 7 der 8 Patienten konnten letztendlich erfolgreich transplantiert werden. Fur kleinere Kinder wurde inzwischen ein Unterstutzungssystem vom Typ Medos mit einer Ventrikelgrose von 25 bzw. 10 ml entwickelt. more...

Der kardiogene Schock nach akutem Myokardinfarkt weist trotz Fruhreperfusionsmasnahmen eine hohe Letalitat auf. Oft gelingt eine hamodynamische Stabilisierung nur durch den Einsatz mechanischer Kreislaufunterstutzungssysteme. Besteht der kardiogene Schock trotz hochdosierter medikamentoser Therapie und Implantation perkutaner Unterstutzungssysteme weiter und findet sich intraoperativ eine ausgedehnte Schadigung des Myokards ohne eine Moglichkeit der Erholung, so ist die Indikation zur Implantation eines sog. „total artificial heart“ gegeben. Wir berichten uber unsere ersten Erfahrungen mit dieser aufwendigen und innovativen Behandlungsstrategie. Bei funf Patienten (mannlich, Durchschnittsalter 50 Jahre) wurde das Cardio-West total artificial heart implantiert. Alle Patienten befanden sich im irreversiblen kardiogenen Schock trotz hochdosierter Katecholamintherapie und intraaortaler Ballonpumpe und/oder femoro- femoralem Bypass. Bei allen Patienten waren Fruhreperfusionsmasnahmen durchgefuhrt worden. Es kam in allen Fallen nach der Implantation des CardioWest- Systems zu einer raschen Erholung aller dysfunktionellen Organsysteme. Vier der funf Patienten konnten nach im Mittel 156 Tagen Unterstutzungsdauer erfolgreich transplantiert werden. Ein Patient verstarb nach 167-tagiger Unterstutzung an embolisch bedingten Darmnekrosen, nachdem die ubliche Antikoagulation mit Marcumar aufgrund von Darmblutungen eingestellt werden musste. Zusammengefasst rechtfertigen die ersten Ergebnisse die aufwendige Behandlungsstrategie bei den jungen Patienten, die ansonsten innerhalb weniger Stunden verstorben waren. more...