Treatment Strategies and Outcomes of Right Ventricular Failure Post Left Ventricular Assist Device Implantation: An INTERMACS Analysis.

Right heart failure (RHF) management after left ventricular assist device (LVAD) implantation includes inotropes, right ventricular mechanical support, and heart transplantation. The purpose of this study is to compare different RHF treatment strategies in patients with a magnetically levitated centrifugal LVAD. A total of 6,632 Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) patients from 2013 to 2020 were included. Of which, 769 (69.6%) patients (group 1) were supported with inotropes (≥14 days post-LVAD implantation), 233 (21.1%) patients (group 2) were supported with temporary right ventricular assist device (RVAD) that was implanted during LVAD implant, 77 (7.0%) patients (group 3) with durable centrifugal RVAD implanted during the LVAD implant, and 26 (2.4%) patients (group 4) were supported with RVAD (temporary or permanent), which was implanted at a later stage. Groups 1 and 4 had higher survival rates in comparison with group 2 (hazard ratio [HR] = 0.513, 95% confidence intervals [CIs] = 0.402-0.655, p < 0.001, versus group 1) and group 3 (HR = 0.461, 95% CIs = 0.320-0.666, p < 0.001, versus group 1). Patients in group 3 showed higher heart transplantation rates at 12 and 36 months as compared with group 1 (40.4% and 46.6% vs. 21.9% and 37.4%, respectively), group 2 (40.4% and 46.6% vs. 25.8% and 39.3%, respectively), and group 4 (40.4% and 46.6% vs. 3.8% and 12.0%, respectively). Severe RHF post-LVAD is associated with poor survival. Patients with LVAD who during the perioperative period are in need of right ventricular temporary or durable mechanical circulatory support constitute a group at particular risk. Improvement of devices tailored for right ventricular support is mandatory for further evolution of the field.

Diagnostic stewardship for human immunodeficiency virus (HIV) testing using computerized physician order entry.

Altering the appearance of a computerized physician order entry (CPOE) interface reduces misuse of an HIV diagnostic test by 87%, demonstrating that CPOE design is a key component of diagnostic stewardship. Collaboration between infectious disease providers, clinical laboratorians, and information technology (IT) professionals can result in improved quality and decreased costs.

Omecamtiv Mecarbil in Black Patients With Heart Failure and Reduced Ejection Fraction: Insights From GALACTIC-HF.

BACKGROUND: Omecamtiv mecarbil improves cardiovascular outcomes in patients with heart failure (HF) with reduced ejection fraction (EF). Consistency of drug benefit across race is a key public health topic. OBJECTIVES: The purpose of this study was to evaluate the effect of omecamtiv mecarbil among self-identified Black patients. METHODS: In GALACTIC-HF (Global Approach to Lowering Adverse Cardiac Outcomes Through Improving Contractility in Heart Failure) patients with symptomatic HF, elevated natriuretic peptides, and left ventricular ejection fraction (LVEF) ≤35% were randomized to omecamtiv mecarbil or placebo. The primary outcome was a composite of time to first event of HF or cardiovascular death. The authors analyzed treatment effects in Black vs White patients in countries contributing at least 10 Black participants. RESULTS: Black patients accounted for 6.8% (n = 562) of overall enrollment and 29% of U.S. enrollment. Most Black patients enrolled in the United States, South Africa, and Brazil (n = 535, 95%). Compared with White patients enrolled from these countries (n = 1,129), Black patients differed in demographics, comorbid conditions, received higher rates of medical therapy and lower rates of device therapies, and experienced higher overall event rates. The effect of omecamtiv mecarbil was consistent in Black vs White patients, with no difference in the primary endpoint (HR = 0.83 vs 0.88, P-interaction = 0.66), similar improvements in heart rate and N-terminal pro-B-type natriuretic peptide, and no significant safety signals. Among endpoints, the only nominally significant treatment-by-race interaction was the placebo-corrected change in blood pressure from baseline in Black vs White patients (+3.4 vs -0.7 mm Hg, P for interaction = 0.02). CONCLUSIONS: GALACTIC-HF enrolled more Black patients than other recent HF trials. Black patients treated with omecamtiv mecarbil had similar benefit and safety compared with White counterparts.

Cardiac Amyloidosis in a Child Presenting with Syncope: The First Reported Case and a Diagnostic Dilemma.

Cardiac amyloidosis is a rare cause of cardiomyopathy, reported exclusively in adults. We report the first known case presenting in childhood. A 12-year-old boy presented with syncope and diagnosed with ventricular non-compaction by echocardiography. Eventual genetic testing confirmed a TTR gene mutation associated with hereditary transthyretin amyloidosis.

National Landscape of Hospitalizations in Patients with Left Ventricular Assist Device. Insights from the National Readmission Database 2010-2015.

The number of patients with left ventricular assist devices (LVAD) has increased over the years and it is important to identify the etiologies for hospital admission, as well as the costs, length of stay and in-hospital complications in this patient group. Using the National Readmission Database from 2010 to 2015, we identified patients with a history of LVAD placement using International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) code V43.21. We aimed to identify the etiologies for hospital admission, patient characteristics, and in-hospital outcomes. We identified a total of 15,996 patients with an LVAD, the mean age was 58 years and 76% were males. The most common cause of hospital readmission after LVAD was heart failure (HF, 13%), followed by gastrointestinal (GI) bleed (11.8%), device complication (11.5%), and ventricular tachycardia/fibrillation (4.2%). The median length of stay was 6 days (3-11 days) and the median hospital costs was $12,723 USD. The in-hospital mortality was 3.9%, blood transfusion was required in 26.8% of patients, 20.5% had acute kidney injury, 2.8% required hemodialysis, and 6.2% of patients underwent heart transplantation. Interestingly, the most common cause of readmission was the same as the diagnosis for the preceding admission. One in every four LVAD patients experiences a readmission within 30 days of a prior admission, most commonly due to HF and GI bleeding. Interventions to reduce HF readmissions, such as speed optimization, may be one means of improving LVAD outcomes and resource utilization.

Heart transplant recipients with confirmed 2019 novel coronavirus infection: The Detroit experience.

A chronic immunosuppressed state as in solid organ transplant recipients is a reported risk factor for the novel 2019 coronavirus infection. Patients with a history of orthotopic heart transplant (OHT) at a tertiary care transplant center in Detroit, Michigan were retrospectively reviewed from March until May 2020. Clinical parameters and outcomes of 5 OHT recipients and one combined heart-lung recipient with confirmed SARS-CoV-2 were obtained. The cohort was predominately African American males with median age of 59 years (interquartile range, 48.25-73.25). All patients were classified as having mild-moderate disease; none required intubation or ICU admission with no deaths. The most common presenting symptoms were fever and shortness of breath 83% (n = 5), followed by cough and chills 67% (n = 4). All admitted patients (n = 5) received hydroxychloroquine and 3 received high-dose steroids. Antimetabolites were held for 2 patients (33.3%). The calcineurin inhibitor trough goal was decreased in only 1 patient; 3 other patients, without change in goal, required calcineurin inhibitor dosage reduction. Two patients requiring readmission presented 7 and 23 days after initial symptoms onset. In conclusion, our experience with OHT patients infected by the SARS-CoV-2 virus did not have an elevated risk of severe infection. Impact of modifying immunosuppression remains unclear.

Clinical characteristics and outcomes of COVID-19 in solid organ transplant recipients: A cohort study.

Solid organ transplant recipients (SOTr) with coronavirus disease 2019 (COVID-19) are expected to have poorer outcomes compared to nontransplant patients because of immunosuppression and comorbidities. The clinical characteristics of 47 SOTr (38 kidneys and 9 nonkidney organs) were compared to 100 consecutive hospitalized nontransplant controls. Twelve of 47 SOTr managed as outpatients were subsequently excluded from the outcome analyses to avoid potential selection bias. Chronic kidney disease (89% vs 57% P = .0007), diabetes (66% vs 33% P = .0007), and hypertension (94% vs 72% P = .006) were more common in the 35 hospitalized SOTr compared to controls. Diarrhea (54% vs 17%, P < .0001) was more frequent in SOTr. Primary composite outcome (escalation to intensive care unit, mechanical ventilation, or in-hospital all-cause mortality) was comparable between SOTr and controls (40% vs 48%, odds ratio [OR] 0.72 confidence interval [CI] [0.33-1.58] P = .42), despite more comorbidities in SOTr. Acute kidney injury requiring renal replacement therapy occurred in 20% of SOTr compared to 4% of controls (OR 6 CI [1.64-22] P = .007). Multivariate analysis demonstrated that increasing age and clinical severity were associated with mortality. Transplant status itself was not associated with mortality.

Pulmonary Function Testing and Outcomes after Left Ventricular Assist Device Implantation.

BACKGROUND: Pulmonary function testing (PFT) is often done during workup prior to left ventricular assist devices (LVAD), but its utility for predicting outcomes and changes in pulmonary function post-LVAD is not well established. We assessed the association of baseline PFT metrics with outcomes after LVAD, and quantified the changes in PFTs post-LVAD. METHODS AND RESULTS: A retrospective study of 178 patients receiving continuous flow LVADs was conducted. A total of 129 subjects had baseline PFT data and 54 of these had repeat tests after LVAD. We collected PFT data (FEV1, FVC, FEV1/FVC ratios, and DLCO) at baseline and post-LVAD, and tested the association with survival, right heart failure, quality of life (Kansas City Cardiomyopathy Questionnaire [KCCQ]) and functional capacity (six-minute walking distance [6MWD]). Proportional hazards and linear regressions determined relationships between baseline PFT data and survival time and functional outcomes, respectively. Paired t-tests compared pre- and post- LVAD PFT variables. There was no association of baseline PFT parameters with survival time post-LVAD (all P > .2), nor the incidence of perioperative RV failure (all P > .15). There were no significant associations of the baseline PFT metrics with the change in KCCQ or 6MWD.  There were statistically significant declines in FEV1, FEV1/FVC ratio, and DLCO after LVAD (P < .05). CONCLUSION: In this single center study, there was no relationship between baseline PFTs and post-LVAD outcomes, and PFT parameters often worsened after LVAD. Further studies are needed to determine whether PFTs are useful in this setting, and what, if any, impact LVAD therapy has on pulmonary function.

Sleep and self-care correlates before and after implantation of a left-ventricular assist device (LVAD).

The impact of sleep on LVAD patients' self-care behaviors is unknown. This study examined the patterns and changes of patients sleep quality (SQ), daytime sleepiness (DS), instrumental activities of daily living (IADL), and self-care capability (SCC) before and after LVAD. In addition, the relationships among these variables were explored. This observational study consisted of 38 subjects from two VAD Centers in Michigan. The subjects completed self-reported demographics and psychometrically sound SQ, DS, IADL, and SCC questionnaires before LVAD implant and at 1, 3, and 6 months after implant. Data were analyzed using descriptive statistics, linear mixed models, and partial least square models. Subjects (mean age, 56.3 ± 10.3 years) were predominantly white (63%), male (68%), married (60%), and living with caregivers (92%). Over 70% had axial flow LVADs implanted as bridge-to-transplant (55%). Subjects' SQ was poor throughout the study period, along with high normal-to-excessive levels of DS. Problems with IADL before implant were significantly reduced at 1 through 6 months after implant. SCC ranged from "good" to "excellent" before and after implant. Significant relationships between SQ and IADL (ß = 0.43, p < 0.01) and DS and SCC (ß = - 0.62, p < 0.01) were found. In conclusion, poor SQ and high degrees of DS were prevalent before and up to 6 months after LVAD implant. The data inferred that the improvement in IADL was associated with an improvement in SQ. Research is needed to clarify the negative impact of DS on SCC and explain the contributions of caregivers on patients' SCC over time.

Intracranial Hemorrhage in Patients with a Left Ventricular Assist Device.

BACKGROUND: There is a dearth of literature regarding management and outcomes of patients with a left ventricular assist device (LVAD) for advanced heart failure who develop intracranial hemorrhage (ICH). We conducted a case series from 2 centers highlighting patient outcomes and prognostic factors to help clinicians better understand and care for these high-risk patients. METHODS: A case series from 2 large-volume institutions (defined as large by the Nationwide Inpatient Sample hospital size, i.e., >500 beds both with Departments of Neurosurgery and Advanced Heart Failure-Cardiology) was conducted to clarify the prognosis of patients with an LVAD and ICH. We included patients who were being treated with an LVAD who developed ICH. Patient-specific demographics and data regarding heart failure and intracranial hemorrhage characteristics were collected and analyzed to determine which factors contributed to overall survival. RESULTS: We analyzed 59 unique ICHs in patients being treated with an LVAD for heart failure. Initial Glasgow Coma Scale score, presence of midline shift, and ICH size were factors found to be predictive of mortality. One institution had a sicker patient population including patients with ICH with lower Glasgow Coma Scale score, presence of midline shift, and greater hemorrhage size, which led to overall higher mortality compared with the second institution. CONCLUSIONS: Patients being treated with an LVAD who develop ICH have poor outcomes. Predictive factors for same-admission mortality are lower initial Glasgow Coma Scale score, presence of midline shift, and greater ICH volume.

Impact of Preoperative Atrial Fibrillation on Postoperative Thromboembolic Events After Left Ventricular Assist Device Implantation.

BACKGROUND: The incidence of atrial fibrillation (AF) among patients undergoing left ventricular assist device (LVAD) implantation is high. However, the impact of AF on clinical outcomes has not been clarified. We reviewed our 9-year experience of continuous flow (CF) LVADs to determine the impact of preoperative AF on stroke, device thrombosis, and survival. METHODS: Between March 2006 and May 2015, 231 patients underwent implantation of 240 CF LVADs, 127 (52.9%) as bridge to transplantation and 113 (47.1%) as destination therapy. Effect of AF on postoperative outcomes was assessed by using Kaplan-Meier survival and Cox proportional hazard regression. RESULTS: There were 78 patients (32.5%) with preoperative AF with a mean age of 55.7 ± 11.4 years. A similar incidence of stroke was found in patients with and without AF, 12.8% versus 16.0%, respectively (p = 0.803). Survival was similar, with 1-, 6-, 12-, and 24-month survivals of 96.2%, 91.7%, 84.5%, and 69.2%, respectively, for AF patients, versus 93.1%, 85.0%, 79.4%, and 74.1%, respectively, for non-AF patients (p = 0.424). Preoperative AF was not a significant independent predictor of survival with the use of Cox proportional hazard regression (hazard ratio 1.08, 95% confidence interval: 0.66 to 1.76). CONCLUSIONS: Preoperative AF was associated with a similar incidence of postoperative stroke, device thrombosis, and survival. On the basis of these data, it seems unnecessary to perform a left atrial appendage ligation or to alter postoperative anticoagulation in patients with AF undergoing LVAD implantation.

Outcomes on Continuous Flow Left Ventricular Assist Devices: A Single Institutional 9-Year Experience.

BACKGROUND: Continuous-flow left ventricular assist devices (LVADs) have become the standard of care for patients with advanced heart failure. The goal of this study was to review our 9-year institutional experience. METHODS: From March 2006 through May 2015, 231 patients underwent implantation of 240 CF LVADs, HeartMate II LVAD (Thoratec Corp., Pleasanton, CA; n = 205) or HVAD (HeartWare Inc., Framingham, MA; n = 35). Of these, 127 devices (52.9%) were implanted as bridge to transplantation (BTT) and 113 (47.1%) as destination therapy (DT). RESULTS: Mean age was 51.2 ± 11.9 years for BTT patients and 58.2 ± 11.4 years for DT patients (p < 0.001). There was a higher incidence of preoperative diabetes, renal insufficiency, peripheral vascular disease, and previous cardiac operation in DT patients (p < 0.05). Survival was higher for BTT patients, with 1-, 6-, 12-, and 24-month survivals of 91.0%, 90.0%, 88.5%, and 72.1%, respectively, versus 85.3%, 81.1%, 75.6%, and 59.0%, respectively, for DT patients (p = 0.038). Gastrointestinal bleeding was the most common complication (29.6%), followed by right ventricular failure (22.5%) and stroke (15.0%), with a similar incidence for BTT and DT patients. Preoperative liver biopsy (hazard ratio [HR] 2.27, p = 0.036), mechanical support (HR 1.82, p = 0.025), aspartate transaminase (HR 1.07, p = 0.001), and alanine aminotransferase (HR 0.95, p = 0.024) were severe independent predictors of survival in multivariate analysis. CONCLUSIONS: These data indicate excellent survival for BTT and DT patients on long-term LVAD support. However, for LVAD therapy to become a plausible alternative to heart transplantation, we need to further decrease the incidence of postoperative complications.

Progressive Left Ventricular Hypertrophy after Heart Transplantation: Insights and Mechanisms Suggested by Multimodal Images.

Immunosuppression is the typical measure to prevent rejection after heart transplantation. Although rejection is the usual cause of cardiac hypertrophy, numerous other factors warrant consideration. Calcineurin inhibitors rarely cause hypertrophic cardiomyopathy; the few relevant reports have described children after orthotopic kidney or liver transplantation. We present the case of a 73-year-old woman, an asymptomatic orthotopic heart transplantation patient, in whom chronic immunosuppression with prednisone and cyclosporine apparently caused a phenotype of hypertrophic cardiomyopathy. The natural course of her midapical hypertrophy was revealed by single-photon-emission computed tomography, positron-emission tomography, and 2-dimensional echocardiography. Clinicians and radiographers should be alert to progressive left ventricular hypertrophy and various perfusion patterns in heart transplantation patients even in the absence of underlying coronary artery disease. Toward this end, we recommend that advanced imaging methods be used to their fullest extent.

Prognostic value of cardiopulmonary exercise testing in heart failure with preserved ejection fraction. The Henry Ford HospITal CardioPulmonary EXercise Testing (FIT-CPX) project.

BACKGROUND: Although cardiopulmonary exercise (CPX) testing in patients with heart failure and reduced ejection fraction is well established, there are limited data on the value of CPX variables in patients with HF and preserved ejection fraction (HFpEF). We sought to determine the prognostic value of select CPX measures in patients with HFpEF. METHODS: This was a retrospective analysis of patients with HFpEF (ejection fraction ≥ 50%) who performed a CPX test between 1997 and 2010. Selected CPX variables included peak oxygen uptake (VO2), percent predicted maximum oxygen uptake (ppMVO2), minute ventilation to carbon dioxide production slope (VE/VCO2 slope) and exercise oscillatory ventilation (EOV). Separate Cox regression analyses were performed to assess the relationship between each CPX variable and a composite outcome of all-cause mortality or cardiac transplant. RESULTS: We identified 173 HFpEF patients (45% women, 58% non-white, age 54 ± 14 years) with complete CPX data. During a median follow-up of 5.2 years, there were 42 deaths and 5 cardiac transplants. The 1-, 3-, and 5-year cumulative event-free survival was 96%, 90%, and 82%, respectively. Based on the Wald statistic from the Cox regression analyses adjusted for age, sex, and ß-blockade therapy, ppMVO2 was the strongest predictor of the end point (Wald χ(2) = 15.0, hazard ratio per 10%, P < .001), followed by peak VO2 (Wald χ(2) = 11.8, P = .001). VE/VCO2 slope (Wald χ(2)= 0.4, P = .54) and EOV (Wald χ(2) = 0.15, P = .70) had no significant association to the composite outcome. CONCLUSION: These data support the prognostic utility of peak VO2 and ppMVO2 in patients with HFpEF. Additional studies are needed to define optimal cut points to identify low- and high-risk patients.

Heart Rate and V˙O2 Concordance in Continuous-Flow Left Ventricular Assist Devices.

UNLABELLED: The American College of Sports Medicine currently recommends the HR reserve (HRR) method to guide exercise in individuals who have heart failure with reduced ejection fraction. This recommendation is based on the known association between %HRR and percentage of V˙O2 reserve (%V˙O2R) in this population. However, to our knowledge, no studies exist regarding this relation in individuals with a left ventricular assist device (LVAD). PURPOSE: This article aimed to describe the relation between V˙O2 and surrogate markers of exercise intensity among patients with LVAD. METHODS: Patients with continuous-flow LVAD (n = 24, seven females) completed a symptom-limited graded exercise test on a treadmill. HR and V˙O2 were measured continuously and averaged every 20 s. Regression equations were determined using a generalized estimating equation to predict %V˙O2R from %HRR, Borg RPE, and LVAD flow, overall and stratified by presence of pacing. RESULTS: Although the association between %HRR and %V˙O2R was good (R = 0.75), the slope and y-intercept for %HRR versus %V˙O2R was different from the line of identity (P = 0.002). However, when paced subjects were excluded (n = 8) from the analysis, there was no significant difference between the slope and y-intercept (= 0.036 + 0.937 × %HRR; SEE, 2%; P = 0.052). RPE showed a strong association with %V˙O2R (R = 0.84), whereas LVAD flow showed a weak (albeit statistically significant) association (R = 0.05). Both had slopes and y-intercepts that were different from the line of identity (P < 0.05). CONCLUSIONS: In patients with LVAD who are not paced during exercise, the use of %HRR is a good predictor of %V˙O2R. However, for patients in this population who are also paced during exercise, RPE is a suitable surrogate measure of exercise intensity.

Short and long term outcomes of 200 patients supported by continuous-flow left ventricular assist devices.

AIM: To study the institutional experience over 8 years with 200 continuous-flow (CF) - left ventricular assist devices (LVAD). METHODS: We evaluated our institution's LVAD database and analyzed all patients who received a CF LVAD as a bridge to transplant (BTT) or destination therapy from March 2006 until June 2014. We identified 200 patients, of which 179 were implanted with a HeartMate II device (Thoratec Corp., Pleasanton, CA) and 21 received a Heartware HVAD (HeartWare Inc., Framingham, MA). RESULTS: The mean age of our LVAD recipients was 59.3 years (range 17-81), 76% (152/200) were males, and 49% were implanted for the indication of BTT. The survival rate for our LVAD patients at 30 d, 6 mo, 12 mo, 2 years, 3 years, and 4 years was 94%, 86%, 78%, 71%, 62% and 45% respectively. The mean duration of LVAD support was 581 d (range 2-2595 d). Gastrointestinal bleeding (was the most common adverse event (43/200, 21%), followed by right ventricular failure (38/200, 19%), stroke (31/200, 15%), re exploration for bleeding (31/200, 15%), ventilator dependent respiratory failure (19/200, 9%) and pneumonia (15/200, 7%). Our driveline infection rate was 7%. Pump thrombosis occurred in 6% of patients. Device exchanged was needed in 6% of patients. On multivariate analysis, preoperative liver dysfunction, ventilator dependent respiratory failure, tracheostomy and right ventricular failure requiring right ventricular assist device support were significant predictors of post LVAD survival. CONCLUSION: Short and long term survival for patients on LVAD support are excellent, although outcomes still remain inferior compared to heart transplantation. The incidence of driveline infections, pump thrombosis and pump exchange have declined significantly in recent years.

Effect of Preoperative Albumin Levels on Outcomes in Patients Undergoing Left Ventricular Device Implantation.

Hypoalbuminemia is a well-known predictor of morbidity and mortality in cardiac surgery. Our aim was to establish the impact of serum albumin on outcomes after left ventricular assist device (LVAD) implantation. This was a single-institution retrospective review, including all patients who underwent LVAD implantation between March 2006 and June 2014. Two hundred patients were included in the analysis. Mean serum albumin was 3.27 ± 0.47 g/dl, with 7% in the low albumin group (<2.5 mg/dl), 67.5% in the mid-range (2.5-3.5 mg/dl), and 25.5% in the normal albumin groups (> 3.5 mg/dl). Lower albumin was associated with a significant increase in postoperative renal failure (42.9 vs. 16.5 vs. 17.3%; p = 0.05) and prolonged hospitalization (median 28.5 vs. 16 vs. 15.5 days; p = 0.008). Six month, 1 year, and 5 year survival was 79%, 79%, and 49% with low, 84%, 78%, and 51% with mid-range, and 94%, 88%, and 60% with normal albumin, respectively (p = 0.22). Preoperative hypoalbuminemia is associated with postoperative acute renal failure (ARF) and prolonged hospitalization after LVAD implantation, with no effect on overall survival. Hypoalbuminemia is most likely a marker of advanced disease and should not, in itself, be considered a contraindication to LVAD candidacy.

Comprehensive analysis of cardiopulmonary exercise testing and mortality in patients with systolic heart failure: the Henry Ford Hospital cardiopulmonary exercise testing (FIT-CPX) project.

BACKGROUND: Many studies have shown a strong association between numerous variables from a cardiopulmonary exercise (CPX) test and prognosis in patients with heart failure with reduced ejection fraction (HFrEF). However, few studies have compared the prognostic value of a majority of these variables simultaneously, so controversy remains regarding optimal interpretation. METHODS AND RESULTS: This was a retrospective analysis of patients with HFrEF (n = 1,201; age = 55 ± 13 y; 33% female) and a CPX test from 1997 to 2010. Thirty variables from a CPX test were considered in separate adjusted Cox regression analyses to describe the strength of the relation of each to a composite end point of all-cause mortality, left ventricular assist device implantation, or heart transplantation. During a median follow-up of 3.8 years, there were 577 (48.0%) events. The majority of variables were highly significant (P < .001). Among these, percentage of predicted maximum V˙O2 (ppMV˙O2; Wald = 203; P < .001; C-index = 0.73) was similar to VE-VCO2 slope (Wald = 201; P < .001; C = 0.72) and peak V˙O2 (Wald = 161; P < .001; C = 0.72). In addition, there was no significant interaction observed for peak respiratory exchange ratio <1 vs ≥1. CONCLUSIONS: Consistent with prior studies, many CPX test variables were strongly associated with prognosis in patients with HFrEF. The choice of which variable to use is up to the clinician. Renewed attention should be given to ppMV˙O2, which appears to be highly predictive of survival in these patients.