S.L. Myers

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.

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.

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.

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.

Pump thrombosis in the Thoratec HeartMate II device: An update analysis of the INTERMACS Registry.

BACKGROUND Pump thrombosis in durable continuous-flow pumps is a barrier to long-term mechanical circulatory support. Earlier Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) data identified an increasing risk of pump thrombosis in recent years with the HeartMate II (HMII) left ventricular assist device. The current analysis examines pump thrombosis in the patient cohort extended through June 2014. METHODS The INTERMACS identified 9,808 adult patients from 144 institutions receiving a primary HMII implant between April 2008 and June 30, 2014. Pump thrombosis was identified at time of explant, transplant or death. Risk factors for pump thrombosis were examined by multivariable analysis in the hazard function domain. The association between pump thrombosis and implant year was modeled in the hazard domain. RESULTS Parametric hazard modeling of thrombosis by year of implant identified an increasing risk of pump thrombosis from 2009 through 2013, followed by a decrease in the risk during the first half of 2014, which was most apparent during the first 3 months post-implant. Risk factors for pump thrombosis included younger age (p < 0.001), higher body mass index (p = 0.02), history of non-compliance (p = 0.004), severe right heart failure (p = 0.02), later date of implant (p < 0.0001), and elevated lactate dehydrogenase during the first month post-implant (p < 0.0001). Subsequent pump thrombosis was more likely if the initial pump exchange indication was pump thrombosis (p < 0.0001). CONCLUSIONS The small, but progressive increase in the incidence of pump thrombosis observed between 2010 and 2013 with the HMII pump had reversed somewhat in the first half of 2014. Identification of marked elevation of lactate dehydrogenase during the first month offers an opportunity for early intervention strategies.

Overall quality of life improves to similar levels after mechanical circulatory support regardless of severity of heart failure before implantation

BACKGROUND The severity of pre-implantation heart failure may affect post-implantation health-related quality of life (HRQOL). The purpose of our study was to examine differences in HRQOL from before mechanical circulatory support (MCS) through 1 year after surgery by Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) patient profiles. METHODS Data from 1,559 adults with advanced heart failure who received primary continuous-flow pumps between June 23, 2006, and March 31, 2010, and were enrolled in INTERMACS were analyzed. HRQOL data were collected using the EQ-5D-3L survey before implantation and at 3, 6, and 12 months after implantation. Statistical analyses included chi-square and t-tests, using all available data for each time period. Paired t-tests and sensitivity analyses were also conducted. RESULTS HRQOL was poor before MCS implantation among patients with INTERMACS profiles 1 to 7 and significantly improved after MCS implantation for all profiles. Stratified by INTERMACS profile, problems within each of the 5 dimensions of HRQOL (i.e., mobility, self-care, usual activities, pain, and anxiety/depression) generally decreased from before to after implantation. By 6 months after implantation, patients with all INTERMACS profiles reported similar frequencies of problems for all HRQOL dimensions. Paired t-tests and sensitivity analyses supported almost all of our findings. CONCLUSIONS HRQOL is poor among advanced heart failure patients with INTERMACS profiles 1 to 7 before MCS implantation and improves to similar levels for patients who remained on MCS 1 year after surgery. Patients have problems in HRQOL dimensions before and after MCS; however, the frequency of reporting problems decreases for all dimensions within most profiles across time.

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.

Change in Health-related Quality of Life from Before to After Destination Therapy Mechanical Circulatory Support is Similar for Older and Younger Patients: Analyses from INTERMACS

BACKGROUND Destination therapy left ventricular assist devices (DT LVADs) are being implanted in older adults on an increasing basis. Older patients have a higher risk for mortality and morbidity post-LVAD, which may impact their health-related quality of life (HRQOL). We aimed to determine the change in HRQOL by age from before implant to 1 year after DT LVAD implant and identify factors associated with the change. METHODS Data were collected from 1,470 continuous-flow DT LVAD patients at 108 institutions participating in INTERMACS from January 21, 2010 to March 31, 2012. Patients were divided into three cohorts: <60 years of age (n = 457); 60 to 69 years of age (n = 520); and ≥70 years of age (n = 493). HRQOL was measured using the generic EuroQol instrument (EQ-5D-3L). Data were collected pre-implant and 3, 6 and 12 months post-implant. Statistical analyses included descriptive statistics, Kaplan-Meier survival analyses and multivariable regression analyses. RESULTS HRQOL improved in all patients. Generally, older patients reported better HRQOL than younger patients pre-implant (≥70 years: mean 40; 60 to 69 years: mean 33; and <60 years: mean 31; p < 0.0001) and 1 year post-implant (≥70 years: mean 77; 60 to 69 years: mean 72; <60 years: mean 70; p = 0.01) using the EQ-5D visual analog scale (VAS), with 0 = worst imaginable health state and 100 = best imaginable health state. The magnitude of improvement in EQ-5D scores from pre-implant to 1-year post-LVAD implant was similar in all age groups (≥70 years: mean change 33; 60 to 69 years: mean change 35; <60 years: mean change 35; p = 0.77). Factors associated with improvement in HRQOL from before to 1 year after implant were a lower VAS score pre-implant and fewer rehospitalizations post-implant (R(2) = 61.3%, p < 0.0001). CONCLUSIONS Older patients reported better HRQOL than younger patients before and after LVAD implantation. The magnitude of improvement was similar for all age groups, with >70% of all patients showing clinically significant increases (>10 points on the VAS). Rehospitalization appears to reduce the magnitude of improvement.

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.