Right Heart Failure Following Left Ventricular Device Implantation: Natural History, Risk Factors, and Outcomes: An Analysis of the STS INTERMACS Database.

BACKGROUND: Our current understanding of right heart failure (RHF) post-left ventricular assist device (LVAD) is lacking. Recently, a new Interagency Registry for Mechanically Assisted Circulatory Support definition of RHF was introduced. Based on this definition, we investigated natural history, risk factors, and outcomes of post-LVAD RHF. METHODS: Patients implanted with continuous flow LVAD between June 2, 2014, and June 30, 2016 and registered in the Interagency Registry for Mechanically Assisted Circulatory Support/Society of Thoracic Surgeons Database were included. RHF incidence and predictors, and survival after RHF were assessed. The manifestations of RHF which were separately analyzed were elevated central venous pressure, peripheral edema, ascites, and use of inotropes. RESULTS: Among 5537 LVAD recipients (mean 57±13 years, 49% destination therapy, support 18.9 months) prevalence of 1-month RHF was 24%. Of these, RHF persisted at 12 months in 5.3%. In contrast, de novo RHF, first identified at 3 months, occurred in 5.1% and persisted at 12 months in 17% of these, and at 6 months occurred in 4.8% and persisted at 12 months in 25%. Higher preimplant blood urea nitrogen (ORs,1.03-1.09 per 5 mg/dL increase; P<0.0001), previous tricuspid valve repair/replacement (ORs, 2.01-10.09; P<0.001), severely depressed right ventricular systolic function (ORs,1.17-2.20; P=0.004); and centrifugal versus axial LVAD (ORs,1.15-1.78; P=0.001) represented risk factors for RHC incidence at 3 months. Patients with persistent RHF at 3 months had the lowest 2-year survival (57%) while patients with de novo RHF or RHF which resolved by 3 months had more favorable survival outcomes (75% and 78% at 2 years, respectively; P<0.001). CONCLUSIONS: RHF at 1 or 3 months post-LVAD was a common and frequently transient condition, which, if resolved, was associated with relatively favorable prognosis. Conversely, de novo, late RHF post-LVAD (>6 months) was more frequently a persistent disorder and associated with increased mortality. The 1-, 3-, and 6-month time points may be used for RHF assessment and risk stratification in LVAD recipients.

Long-term survival on LVAD support: Device complications and end-organ dysfunction limit long-term success.

BACKGROUND: Preoperative variables can predict short term left ventricular assist device (LVAD) survival, but predictors of extended survival remain insufficiently characterized. METHOD: Patients undergoing LVAD implant (2012-2018) in the Intermacs registry were grouped according to time on support: short-term (<1 year, n = 7,483), mid-term (MT, 1-3 years, n = 5,976) and long-term (LT, ≥3 years, n = 3,015). Landmarked hazard analyses (adjusted hazard ratio, HR) were performed to identify correlates of survival after 1 and 3 years of support. RESULTS: After surviving 1 year of support, additional LVAD survival was less likely in older (HR 1.15 per decade), Caucasian (HR 1.22) and unmarried (HR 1.16) patients (p < 0.05). After 3 years of support, only 3 preoperative characteristics (age, race, and history of bypass surgery, p < 0.05) correlated with extended survival. Postoperative events most negatively influenced achieving LT survival. In those alive at 1 year or 3 years, the occurrence of postoperative renal (creatinine HR MT = 1.09; LT HR = 1.10 per mg/dl) and hepatic dysfunction (AST HR MT = 1.29; LT HR = 1.34 per 100 IU), stroke (MT HR = 1.24; LT HR = 1.42), infection (MT HR = 1.13; LT HR = 1.10), and/or device malfunction (MT HR = 1.22; LT HR = 1.46) reduced extended survival (all p ≤ 0.03). CONCLUSIONS: Success with LVAD therapy hinges on achieving long term survival in more recipients. After 1 year, extended survival is heavily constrained by the occurrence of adverse events and postoperative end-organ dysfunction. The growth of destination therapy intent mandates that future LVAD studies be designed with follow up sufficient for capturing outcomes beyond 24 months.

Evolution of Late Right Heart Failure With Left Ventricular Assist Devices and Association With Outcomes.

BACKGROUND: A revised definition of right heart failure (RHF) for the Society of Thoracic Surgeons Intermacs database of left ventricular assist devices (LVADs) was introduced in June 2014. OBJECTIVES: The purpose of this study was to determine the prevalence and severity of RHF over time and the association of RHF status at 3 months with 12-month outcomes after LVAD. METHODS: All patients in Society of Thoracic Surgeons Intermacs with follow-up and supported at least 3 months with a continuous flow LVAD implanted between June 2, 2014 and March 31, 2017 without a simultaneous RVAD. RHF was defined as both documentation and manifestations of elevated central venous pressures. RESULTS: There were 6,118 patients included with an incidence of RHF at 3, 6, and 12 months postimplant categorized as mild in 5%, 6%, and 6% and moderate in 5%, 3%, and 3%, respectively. For those with no RHF at 3 months, there was a low incidence of subsequent RHF at 6 and 12 months. The lack of RHF at 3 months, compared with mild and moderate RHF, was associated with a lower 12-month cumulative incidence of mortality (6.9% vs 16.7% vs 28.1%; P < 0.0001) and a lower 12-month cumulative incidence of stroke (7.4% vs 9.5% vs 11.0%; P = 0.0095), gastrointestinal bleeding (14.8% vs 24.2% vs 23.6%; P < 0.0001), and rehospitalization (65.2% vs 73.2% vs 71.2%; P < 0.0001). CONCLUSIONS: In patients surviving 3 months with LVAD support alone, mild or moderate RHF occurred in nearly 1 of 10 patients at 12 months. Patients with late RHF had worse survival and a higher cumulative incidence of major adverse events.

Impact of thoracotomy approach on right ventricular failure and length of stay in left ventricular assist device implants: an intermacs registry analysis.

INTRODUCTION: Traditionally, implantation of Left Ventricular Assist Devices (LVADs) is performed via median sternotomy. Recently, less invasive thoracotomy approaches are growing in popularity as they involve less surgical trauma, potentially less bleeding, and may preserve right ventricular function. We hypothesized implantation of LVADs via thoracotomy has less perioperative right ventricular failure (RVF) and shorter postoperative length of stay (LOS). METHODS: Continuous flow LVAD implants from Intermacs between February 6, 2014 - December 31, 2018 were identified. Patients implanted via thoracotomy were propensity matched in a 1:1 ratio with patients implanted via sternotomy. Outcomes were compared between sternotomy and thoracotomy approach and by device type (axial, centrifugal-flow with hybrid levitation (CF-HL), centrifugal-flow with full magnetic levitation devices (CF-FML)). The primary outcome was time to first moderate or severe RVF. Secondary outcomes included survival and LOS. RESULTS: Overall 978 thoracotomy patients were matched with 978 sternotomy patients. Over the study period, 242 thoracotomy patients and 219 sternotomy patients developed RVF with no significant difference in time to first moderate to severe RVF by surgical approach overall (p = 0.27) or within CF-HL (p = 0.36) or CF-FML devices (p = 0.25). Survival did not differ by implant technique (150 deaths in thoracotomy group, 154 deaths in sternotomy group; p = 0.58). However, sternotomy approach was associated with a significantly shorter LOS (17 Vs 18 days, p = 0.009). CONCLUSION: As compared to sternotomy, implantation of continuous flow LVADs via thoracotomy approach does not reduce moderate to severe RVF or improve survival but does reduce post-operative LOS. Device type did not influence outcomes and most centers did a small volume of thoracotomy implants.

Quantifying the impact from stroke during support with continuous flow ventricular assist devices: An STS INTERMACS analysis.

INTRODUCTION: Adverse events, especially strokes, during the implantation of continuous flow durable left ventricular assist devices (LVADs) remain the major barriers to greater application among patients with ambulatory advanced heart failure. METHODS: Between June 2014 and June 2017, a total of 9,489 patients in the Society of Thoracic Surgeons Interagency Registry for Mechanically Assisted Circulatory Support database received 10,285 continuous flow LVADs, with follow-up through June 2018. RESULTS: During the follow-up period, 1,515 (16%) patients suffered 1 or more strokes, with a nearly equal frequency of ischemic and hemorrhagic etiology. The risk of stroke was about 4% in the first month, 9% during the first 6 months, and 14% in the first year. By multivariable hazard function analysis, the major risk factors identified in the early phase were LVAD centrifugal flow device and concomitant cardiac surgery, whereas in the constant phase (longer term), a history of repeated non-compliance was most associated with a stroke event. Using a modulated renewal model, the occurrence of an ischemic and especially a hemorrhagic stroke dominated as risk factors for subsequent mortality. Six-month survival after an ischemic stroke was 70%, and after a hemorrhagic stroke, it was <50%. Disabling stroke as judged by Modified Rankin Score was associated with significantly worse survival at 1 and 2 years compared with strokes with mild or no early disability. CONCLUSIONS: This study confirms the 20% incidence of stroke over the first 2 years with axial flow and hybrid (magnetic and hydrodynamic) levitated centrifugal flow pumps. This study suggests a major increase in 1- and 2-year mortality among those with an initial disabling vs non-disabling stroke. To better understand the impact of strokes after implantation and the effect of prevention and intervention strategies, we need more complete Modified Rankin Scores and quality of life data during the stroke recovery period.

The Society of Thoracic Surgeons Intermacs 2019 Annual Report: The Changing Landscape of Devices and Indications.

BACKGROUND: The field of mechanical circulatory support has been impacted by the approval of new continuous-flow left ventricular assist devices (LVADs) and changes to the United States heart allocation system. METHODS: Primary isolated continuous-flow LVAD implants in The Society of Thoracic Surgeons Intermacs registry from January 2014 through September 2019 were evaluated. Survival and freedom from major adverse events were compared between axial-flow, centrifugal-flow with hybrid levitation (CF-HL), and centrifugal-flow with full magnetic levitation (CF-FML) devices. RESULTS: Of 2603 devices implanted in 2014, 1824 (70.1%) were axial flow and 1213 (46.6%) were destination therapy (DT); through September 2019, 1752 devices were implanted, but only 37 (2.1%) were axial flow and 1230 (70.2%) were DT. Implants were performed in 13,016 patients between 2014 and 2018. Patients receiving implants in 2017-2018 compared with 2014-2016 were more likely to be at Intermacs profile 1 (17.1% vs 14.3%, P < .001) and to have preimplant temporary mechanical circulatory support (34.8% vs 29.3%, P < .001). Overall survival and freedom from major adverse events were higher with CF-FML devices. In multivariable analysis of survival between CF-HL and CF-FML, device type was not a significant early hazard, but the use of CF-HL devices had a late hazard ratio for death of 3.01 (P < .001). CONCLUSIONS: Over the past 5 years, centrifugal-flow LVADs have become the dominant technology and DT the most common implant strategy. While outcomes with CF-FML devices are promising, comparisons with other devices from nonrandomized registry studies should be made with caution.

Biventricular Support With Intracorporeal, Continuous Flow, Centrifugal Ventricular Assist Devices.

BACKGROUND: The incidence of right ventricular dysfunction requiring right ventricular assist device after left ventricular assist device placement has been reported between 10% to 30%. The mortality rate is higher compared with patients who require left ventricular assist device only; the most effective and safest biventricular assist device remains unknown. We aimed to determine the survival outcomes and frequency of adverse events in patients with two durable, intracorporeal, continuous flow centrifugal pumps for support. METHODS: Between November 2012 and June 2015, 38 patients were identified from INTERMACS received durable, intracorporeal continuous flow centrifugal pumps for biventricular support. Pediatric patients were excluded. Mean age was 47 years, and 74% of patients were male. The common primary diagnoses in this cohort were dilated myopathy, idiopathic (37%) and ischemic (16%). RESULTS: Nineteen participating centers implanted devices in 38 patients; 11 patients died with device in place, 9 patients received a heart transplant, and 18 were alive on support with the right ventricular assist device in place. Survival outcomes were 68% at 6 months and 62% at 12 months. The left ventricular assist device was placed in the left ventricle apex in 91% of cases, and in 9%, the location was not specified. The right ventricular assist device was placed in the right ventricle in 50%, right atrium in 37%, and not specified in 13%. The adverse events included infection 50%, bleeding 44%, respiratory failure 31.6%, and malfunction 26.3%; neurologic dysfunction 26.3%; renal dysfunction 18.4%; and arrhythmia 18.4%. CONCLUSIONS: The use of durable, intracorporeal, continuous flow centrifugal pumps for management of advanced biventricular heart failure is associated with high morbidity and mortality. Further investigation of this device configuration is warranted.

Concomitant mitral valve procedures in patients undergoing implantation of continuous-flow left ventricular assist devices: An INTERMACS database analysis.

BACKGROUND: Management of existing mitral valve (MV) disease in patients undergoing left ventricular assist device (LVAD) implantation remains controversial. METHODS: Among continuous-flow LVAD patients with moderate to severe mitral regurgitation entered into the Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) database between April 2008 and March 2014 (n = 4,930), outcomes were compared between patients who underwent MV repair (MVr, n = 252), MV replacement (MVR, n = 11) and no MV procedure (no MVP, n = 4,667). Impact on survival was analyzed by stratified actuarial and hazard function multivariable methodology. Post-operative functional capacity and quality of life were assessed. RESULTS: Patients who underwent MVPs had higher pre-operative pulmonary vascular resistance (3.6 ± 2.9 vs 2.9 ± 2.6 Wood units; p = 0.0006) and higher pulmonary artery systolic pressures (55.1 ± 13.8 vs 51.5 ± 14.0 mm Hg; p = 0.0003). Two-year survival was 76% for patients with concomitant MVr, 57% for those with MVR and 71% for those with no MVP (p = 0.15). By multivariable analysis, neither MVr nor MVR affected early or late survival. Although improvements in post-operative functional status as evaluated by 6-minute walk distances were comparable across groups, visual analog score assessments of quality of life suggested a benefit of concomitant MVPs at 1-year post-implant (79.00 ± 1.73 vs 74.45 ± 0.51; p = 0.03), with fewer re-admissions observed for MVP patients (p < 0.0001). CONCLUSIONS: Concomitant MVPs are not associated with increased survival overall. However, MVPs are associated with benefits in terms of reduced hospital re-admission and improved quality of life in select patients.

Eighth annual INTERMACS report: Special focus on framing the impact of adverse events.

BACKGROUND: The Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) database now includes >20,000 patients from >180 hospitals. METHODS: The eighth annual report of INTERMACS updates the first decade of patient enrollment. RESULTS: In the current era, >95% of implants are continuous flow devices. Overall survival continues to remain >80% at 1 year and 70% at 2 years. Review of major adverse events shows minimal advantage for patients with ambulatory heart failure pre-implant. Stroke, major infection, and continued inotrope requirement during the first 3 months have a major effect on subsequent survival. CONCLUSIONS: Greater application of durable devices to patients with ambulatory heart failure will mandate more effective neutralization or prevention of major adverse events.

Seventh INTERMACS annual report: 15,000 patients and counting.

The seventh annual report of the Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) summarizes the first 9 years of patient enrollment. The Registry includes >15,000 patients from 158 participating hospitals. Trends in device strategy, patient profile at implant and survival are presented. Risk factors for mortality with continuous-flow pumps are updated, and the major causes/modes of death are presented. The adverse event burden is compared between eras, and health-related quality of life is reviewed. A detailed analysis of outcomes after mechanical circulatory support for ambulatory heart failure is presented. Recent summary data from PediMACS and MedaMACS is included. With the current continuous-flow devices, survival at 1 and 2 years is 80% and 70%, respectively.

A multicenter analysis of clinical hemolysis in patients supported with durable, long-term left ventricular assist device therapy.

BACKGROUND: Despite the beneficial effects of mechanical circulatory support (MCS), the majority of patients ultimately will have an adverse event. Although hemolysis is common among temporary devices, the incidence and clinical significance of hemolysis in patients managed with long-term, durable left ventricular assist device (LVAD) therapy is largely unknown. METHODS: Data were obtained from the Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS). All adults who received a continuous-flow LVAD (CF-LVAD) between June 2006 and March 2012 were included. A hemolytic event was defined as a plasma-free hemoglobin >40 mg/dl in association with clinical signs of hemolysis occurring at least 72 hours after LVAD implant. Descriptive statistics, time-dependent analyses and multivariable modeling were employed for statistical purposes. RESULTS: A total of 4,850 patients followed for a mean of 11.1 months comprised the final study population. There were 340 hemolytic events in 260 patients. Freedom from hemolysis was 97% at 3 months, 94% at 1 year and 91% at 2 years. Mean time from implant to first hemolysis event was 7.4 months. Younger age (<60 years) was independently associated with greater hemolysis (p < 0.001). Thrombotic device malfunction, device exchange and mortality were all significantly higher after hemolysis, with the greatest risk for each occurring within 6 months. CONCLUSIONS: Hemolysis is not a rare event after CF-LVAD implantation and is associated with an early increase in morbidity and death. Future study should focus on other device and implant characteristics that may lead to hemolytic events, as well as appropriate strategies for managing affected patients.

Concomitant aortic valve procedures in patients undergoing implantation of continuous-flow left ventricular assist devices: An INTERMACS database analysis.

BACKGROUND: Management of existing aortic insufficiency (AI) and mechanical aortic valves in patients undergoing left ventricular assist device (LVAD) implantation remains controversial. Surgical options to address these issues include closure, repair or replacement of the valve. METHODS: Continuous-flow LVAD/biventricular VAD patients entered into the INTERMACS database between June 2006 and December 2012 were included (n = 5,344) in this analysis. Outcomes were compared between patients who underwent aortic valve (AV) closure (n = 125), repair (n = 95) and replacement (n = 85). RESULTS: Among patients who underwent an AV procedure, actuarial survival was significantly reduced for AV closures (63.2%) compared with AV repairs (76.8%) and replacements (71.8%) (p = 0.0003). Differences were greater between groups when only INTERMACS Level 1 or 2 patients were analyzed (p = 0.003). After multivariate adjustment, AV closure remained a significant risk factor for mortality (hazard ratio = 1.87, 95% confidence interval 1.39 to 2.53, p < 0.0001). At 6 to 12 months post-operatively, moderate to severe AI developed in 19%, 5%, 9% and 10% of patients with available echocardiography who underwent repair, closure, replacement and no intervention, respectively (p < 0.0001). Competing outcomes demonstrate that, at 1-year, fewer patients with AV closures were transplanted compared with patients with repairs/replacements (14% vs 19%). No differences were observed between groups with respect to cause of death, re-hospitalization, right heart failure or stroke. CONCLUSIONS: AV closure was associated with increased mortality when compared with repair or replacement in patients with AI who underwent LVAD insertion. The reasons for this association require further investigation. This is the largest study to date to examine concomitant AV procedures in patients undergoing LVAD insertion.

Predictors of hospital length of stay after implantation of a left ventricular assist device: an analysis of the INTERMACS registry.

BACKGROUND: Few studies have reported on hospital length of stay (LOS) after left ventricular assist device (LVAD) implantation. The purpose of this study was to determine pre- and peri-operative predictors of hospital LOS after LVAD implantation. METHODS: We analyzed adult primary continuous-flow LVAD patients implanted between June 23, 2006 and December 31, 2010 at 105 institutions from the Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS). Retrospective analyses included measures of central tendency, frequencies, correlations and stepwise multivariable regression modeling (p ≤ 0.05). Independent variables included demographic characteristics, pre-implant clinical and behavioral variables and concomitant surgery. RESULTS: Characteristics of the patients (n = 2,200) included: mean age 54.6 ± 12.6 years; 79% male; 69% white; 57% INTERMACS Profile 1 or 2; 37% diabetic; 21% with history of coronary artery bypass graft (CABG); 7% with history of valve surgery; and 37% with concomitant surgery. Median hospital LOS (implant to discharge) was 20 days. Significant predictors of an increased hospital LOS included demographic characteristics (older age and non-white), pre-implant clinical variables (history of CABG or valve surgery, diabetes, ascites, INTERMACS Profiles 1 and 2, low albumin, high blood urea nitrogen, high right atrial pressure) and concomitant surgery, explaining 12% variance (F = 22.65, p<0.001). CONCLUSIONS: Demographic characteristics, pre-implant variables and concomitant surgery partially explained hospital LOS after continuous-flow LVAD implant. These variables have implications regarding selection of patients for mechanical circulatory support.

Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) analysis of pump thrombosis in the HeartMate II left ventricular assist device.

BACKGROUND: Pump thrombosis remains an uncommon but potentially catastrophic complication of durable continuous-flow left ventricular assist devices (LVAD). A perceived increase in the incidence of pump thrombosis in the HeartMate II (HMII) LVAD (Thoratec, Pleasanton, CA) by clinicians prompted this analysis of the Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) database. METHODS: Between 2006 and June 2013, 8,988 United States patients aged older than 18 years received a durable LVAD. Of these, 6,910 adult patients from 132 institutions who received a HMII LVAD were entered in the INTERMACS database and constitute the study group for this analysis. RESULTS: Overall survival (with censoring at transplant or explant for recovery) with the HMII LVAD was 80% at 1 year and 69% at 2 years and was not significantly different when stratified by era of implant. Freedom from device exchange or death due to thrombosis decreased from 99% at 6 months in 2009 to 94% in 2012 (p < 0.0001). Multivariable hazard function analysis showed risk factors for pump thrombosis included later implant year (p < 0.0001), younger age (p < 0.0001), higher creatinine (p = 0.002), larger body mass index (p = 0.004), white race (p = 0.0004), left ventricular ejection fraction above 20% (p = 0.02), and higher lactate dehydrogenase level at 1 month (p < 0.0001). Survival (p < 0.0001) and freedom from infection (p = 0.008) and cerebrovascular accident (p < 0.0001) were lower after pump exchange than after primary implant. CONCLUSIONS: Pump exchange or death due to pump thrombosis increased during 2011 and 2012, but the magnitude of the increase remained relatively small. Survival remains high (80% at 1 year) with the HMII LVAD. Risk factor analysis suggests that a number of patient-related factors contribute to the risk of thrombosis. Markedly elevated lactate dehydrogenase in the first month is a predictor of pump thrombosis. This analysis could not examine the potential role of technical factors during implant, such as sub-optimal pump or graft positioning, changes in patient management paradigms with pump speed settings, improved recognition and change in the threshold for pump exchange, or design or production changes with the pump, as contributors to the risk of pump thrombosis.

Increased need for right ventricular support in patients with chemotherapy-induced cardiomyopathy undergoing mechanical circulatory support: outcomes from the INTERMACS Registry (Interagency Registry for Mechanically Assisted Circulatory Support).

OBJECTIVES: The aim of this study was to investigate the use of durable mechanical circulatory support (MCS) in patients with chemotherapy-induced cardiomyopathy (CCMP) and determine their outcomes and survival in comparison to that of other patients with end-stage heart failure treated similarly. BACKGROUND: Patients with end-stage heart failure as a result of CCMP from anthracyclines are often precluded from heart transplantation because of a history of cancer. In such patients, durable MCS may offer an important chance for life prolongation. Yet, there are no data to support the use of MCS in this increasingly prevalent group of patients. METHODS: We searched 3,812 MCS patients from June 2006 through March 2011 in the INTERMACS (Interagency Registry for Mechanically Assisted Circulatory Support) database for the diagnosis of CCMP. We compared characteristics, outcomes, and survival between CCMP patients and patients with nonischemic cardiomyopathy and ischemic cardiomyopathy. RESULTS: Compared with patients with nonischemic cardiomyopathy and ischemic cardiomyopathy, patients with CCMP were overwhelmingly female (72% vs. 24% vs. 13%, p = 0.001), had MCS more often implanted as destination therapy (33% vs. 14% vs. 22%, p = 0.03), required more right ventricular assist device support (19% vs. 11% vs. 6%, p = 0.006), and had a higher risk of bleeding (p = 0001). Survival of CCMP patients was similar to that of other groups. CONCLUSIONS: CCMP patients treated with MCS have survival similar to other MCS patients despite more frequent need for right ventricular assist device support and increased bleeding risk.

Quantifying the effect of cardiorenal syndrome on mortality after left ventricular assist device implant.

BACKGROUND: Comorbidities complicate recovery and contribute to mortality after implant of a left ventricular assist device (LVAD). Coexistent cardiac and renal dysfunction (so-called cardiorenal syndrome) increases the risk of death, both with advanced heart failure and after LVAD implantation. We analyzed patients from the Interagency Registry for Mechanically Assist Circulatory Support to better estimate postimplant mortality according to the severity of renal dysfunction. METHODS: Patients with a continuous-flow LVAD were grouped according to their pre-implant level of renal dysfunction: severe was defined as dialysis and/or estimated glomerular filtration rate (eGFR) < 30 ml/min; moderate if eGFR was 30 to 59 ml/min or blood urea nitrogen (BUN) was > 60 mg/dl; and mild or no renal dysfunction if eGFR was ≥ 60 ml/min and BUN was < 60 mg/dl. RESULTS: Of the 4,917 patients with a continuous-flow LVAD implanted between June 2006 and March 2012, 3,160 (64%) were identified with mild or no renal dysfunction, 1,475 (30%) with moderate dysfunction, and 282 (6%) with severe dysfunction. Worsening renal dysfunction correlated with decreased survival, with nearly a 20% reduction in the 2-year survival going from low to severe dysfunction. The major negative survival effect occurred during the first 3 months. Combination of severe renal dysfunction and cardiogenic shock predicted the highest early mortality. CONCLUSIONS: Pre-implant renal dysfunction predicts higher mortality after LVAD implant. The progressive reduction in survival with higher grades of renal dysfunction supports consideration of LVAD implant before cardiorenal syndrome is advanced. For patients with severe renal dysfunction and other major comorbidities, initial support with a temporary device while awaiting organ recovery before implanting a durable pump could be considered.

Should women receive left ventricular assist device support?: findings from INTERMACS.

BACKGROUND: Small studies have reported women to have worse outcomes and more adverse events after implantation of mechanical circulatory support device compared with men. To further evaluate sex differences in outcome, we used the Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS). METHODS AND RESULTS: There were 401 women (pulsatile devices=78) and 1535 men (pulsatile devices=402) from 89 institutions who were prospectively enrolled into the INTERMACS database for primary implantation of a left ventricular assist device (LVAD) between June 23, 2006, and March 31, 2010. Extensive preimplantation and outcome data were collected on all patients. With a mean follow-up of 7 months, 67 females (17%) died and 250 males (16%) died. There was no statistically significant sex difference in mortality for either pulsatile-flow (P=0.82) or continuous-flow (P=0.95) devices in adjusted and unadjusted models. There were also no statistically significant sex differences with time to first infection, bleeding, or device malfunction. However, female sex was associated with an increased hazard of first neurological event (adjusted hazard ratio, 1.44; 95% CI, 1.05-1.96; P=0.020). CONCLUSIONS: There were no significant sex differences in mortality, time to first infection, bleeding, or device malfunction with either pulsatile- or continuous-flow LVADs. However, women had an increased risk of first neurological event. For urgent/emergent mechanical support, the benefit of LVAD support likely outweighs the risk, but it remains less clear for women undergoing elective LVAD implantation.

Balancing rejection and infection with respect to age, race, and gender: clues acquired from 17 years of cardiac transplantation data.

BACKGROUND: Donor and recipient risk factors for rejection and infection have been well characterized. The contribution of demographic factors, especially age at the time of transplantation to morbidity and mortality due to rejection and infection, is much less well understood. METHODS: Using parametric hazard analysis and multivariate risk-factor equations for infection and rejection events, we quantitatively determined the relationship of fundamental demographic variables (age, race and gender) to infection and rejection. These analyses were conducted with respect to date of transplant and age at the time of transplantation. The patient group consisted of all primary heart transplants performed at the University of Alabama at Birmingham during the years 1990 to 2007 (n = 526). RESULTS: Risk factors for rejection within 12 months post-transplantation were date of transplant (p < 0.0001) and age at the time of transplantation (young adults 10 to 30 years of age, p < 0.0001). Risk factors for infection were date of transplant (p < 0.0001) and age at the time of transplantation (young children and older adults, p < 0.0001). There were three immunosuppressive eras in 1990 to 2007. Notably, although the proportion of patients experiencing rejection and infection events decreased during each successive immunosuppressive era, the relative relationship of infection to rejection, as well as age at the time of transplantation, remained similar into the most recent era. The maximal frequency of rejection events and rejection death occurred among patients transplanted at ages 10 to 30 years. Conversely, the frequency of infection events was minimal within the same group. In the oldest and youngest patients receiving transplants, infection was the predominant cause of death and rates of rejection events decreased. CONCLUSIONS: These data show that evolving immunosuppressive strategies have successfully reduced rejection and infection frequencies, and those patients transplanted at 30 to 60 years of age have the lowest frequency of rejection/infection events. However, individuals transplanted at younger or older ages, especially non-white recipients in the 10- to 30-year age group, experience significantly more infection or rejection. Therefore, programs should increase the level of surveillance in these patients and consider modification of immunosuppressive regimens in order to lower the frequency of infection and rejection events.

Mortality among triazine herbicide manufacturing workers.

Atrazine produces mammary gland cancer in one strain of rats and has been classified as an endocrine modulator. Epidemiologic studies have reported associations between agricultural use of atrazine and several forms of cancer. This study evaluated mortality patterns among workers at a plant that made atrazine and other triazine herbicides. The study covered the time period 1970-1997 and included 2213 people employed for at least 6 mo in operations related to the manufacture or formulation of atrazine and other triazine herbicides at a plant in Louisiana (LA). Vital status was determined for all but six subjects. Standardized mortality ratios (SMRs) with 95% confidence intervals (CIs) compared employees' mortality rates with those of the LA industrial corridor general population. Subjects had a total of 32,473 person-years of observation and a median of 15.8 yr since hire. There were 84 observed/118 expected deaths from all causes combined (SMR = 72, CI = 57-89) and 22/21 total cancer deaths (SMR = 106, CI = 66-160). Subjects had 4/1.1 deaths from non-Hodgkin's lymphoma (SMR = 372, CI = 101-952); this increase was not concentrated in the subgroup with long duration of employment and many years since hire. There were 6/4.8 (SMR = 124, CI = 46-271) digestive cancer and 7/6.3 (SMR = 112, CI = 45-230) lung cancer deaths. Data on other forms of cancer were sparse. This study was limited by its small size, by the relatively young age and short follow-up of its subjects, and by the lack of exposure data. It did not provide evidence that employment in triazine herbicide manufacturing and formulating operations was associated causally with overall or cause-specific mortality.

Cancer incidence among triazine herbicide manufacturing workers.

This study evaluated cancer incidence and prostate specific antigen (PSA) testing among workers at a plant in Louisiana (LA) that made atrazine and other triazine herbicides. The study covered the time period 1985 through 1997 and included 2045 subjects, of whom 757 worked for the company that owned the plant and 1288 were contract employees. Linkage with a population-based cancer registry and review of death certificates and plant medical records identified cancer cases. Standardized incidence ratios (SIRs) with 95% confidence intervals (CIs) compared subjects' cancer incidence rates with those of a regional general population. Plant medical records provided data on the proportion receiving PSA tests among male company employees. Subjects had 46 observed and 40 expected cases of all cancers combined (SIR = 114, CI = 83-152) and had 11/6.3 prostate cancers (SIR = 175, CI = 87-312). The prostate cancer excess was greater in actively working company employees (5/1.3, SIR = 394, CI = 128-920) than in contract employees or inactive company employees (6/5.0, SIR = 119, CI = 44-260) and was limited to men under 60 years of age. Of the 11 prostate cancer cases, nine were diagnosed at an early clinical stage. From 1993 to 1999, the proportion of male company employees who had at least one PSA test was 86% for those who reached 40 years of age while actively working and was 98% for those who reached 45 years of age. The observed prostate cancer increase may have been due to the frequent PSA testing of actively working company employees. There is no epidemiologic or other information that clearly supports a causal relation between atrazine and prostate cancer.