Taking a walk on the heart failure side: comparison of metabolic variables during walking and maximal exertion.

AIMS: Although cardiopulmonary exercise testing (CPET) is the gold standard to assess exercise capacity, simpler tests (i.e., 6-min walk test, 6MWT) are also commonly used. The aim of this study was to evaluate the relationship between cardiorespiratory parameters during CPET and 6MWT in a large, multicentre, heterogeneous population. METHODS: We included athletes, healthy subjects, and heart failure (HF) patients of different severity, including left ventricular assist device (LVAD) carriers, who underwent both CPET and 6MWT with oxygen consumption measurement. RESULTS: We enrolled 186 subjects (16 athletes, 40 healthy, 115 non-LVAD HF patients, and 15 LVAD carriers). CPET-peakV̇O2 was 41.0 [35.0-45.8], 26.2 [23.1-31.0], 12.8 [11.1-15.3], and 15.2 [13.6-15.6] ml/Kg/min in athletes, healthy, HF patients, and LVAD carriers, respectively (P < 0.001). During 6MWT they used 63.5 [56.3-76.8], 72.0 [57.8-81.0], 95.5 [80.3-109], and 95.0 [92.0-99.0] % of their peakV̇O2, respectively. None of the athletes, 1 healthy (2.5%), 30 HF patients (26.1%), and 1 LVAD carrier (6.7%), reached a 6MWT-V̇O2 higher than their CPET-peakV̇O2. Both 6MWT-V̇O2 and walked distance were significantly associated with CPET-peakV̇O2 in the whole population (R2 = 0.637 and R2 = 0.533, P ≤ 0.001) but not in the sub-groups. This was confirmed after adjustment for groups. CONCLUSIONS: The 6MWT can be a maximal effort especially in most severe HF patients and suggest that, in absence of prognostic studies related to 6MWT metabolic values, CPET should remain the first method of choice in the functional assessment of patients with HF as well as in sport medicine.

Oxygen Uptake During Activities of Daily Life in Patients Treated With a Left Ventricular Assist Device.

INTRODUCTION: Oxygen consumption during activities of daily life (ADL) is not described in recipients of left ventricular assist device (LVAD). We aimed to investigate the relation between oxygen consumption during predefined ADLs and measures of functional capacity (FC) in stable-phase LVAD recipients. METHODS: LVADs and controls were matched on gender, age, BMI, smoking status, and ethnicity. VO2 was measured using mobile equipment (K5, Cosmed, Rome, Italy) while putting on vest and LVAD equipment(1), folding towels(2), putting on socks and shoes(3), putting bottles in a cupboard(4), making a bed(5), walking on stairs without(6) and with extra weight(7), and sweeping the floor(8). Submaximal FC was tested by means of 6 minute walk test (6MWT) and peak oxygen uptake (pVO2) to test maximal FC. RESULTS: Fifteen LVAD patients and 16 controls were included; Patients were 61 ± 10years, all males with BMI 28 ± 5kg/m2 and implanted with Heartmate 3 (DT: 60%). PVO2 was 14.9 ± 2.2 ml/kg/min in patients and 39.6 ± 7.7 in controls (p < 0.001). Oxygen consumption expressed as percent of pVO2 for each task in patients vs controls was (%): ADL1: 41 ± 5 vs 21 ± 4, ADL2: 41 ± 6 vs 22 ± 5 %, ADL3: 50 ± 16 vs 24 ± 5%, ADL4: 45 ± 12 vs 22 ± 4, ADL5: 50 ± 8 vs 23 ± 4, ADL6: 66 ± 10 vs 30 ± 4, ADL7: 65 ± 10 vs 31 ± 5, ADL8: 75 ± 10 vs 39 ± 12, (p < 0.001 for all). During 6MWT LVAD patients used 96% ± 8 % of their pVO2. CONCLUSION: Recipients of durable LVADs perform daily life activities at oxygen uptake levels much closer to their peak cardiopulmonary reserve than matched healthy controls.

Prognostic Value of Peak Oxygen Uptake in Patients Supported With Left Ventricular Assist Devices (PRO-VAD).

OBJECTIVES: The purpose of this study was to examine whether peak oxygen uptake (pVO2) and other cardiopulmonary exercise test (CPET)-derived variables could predict intermediate-term mortality in stable continuous flow LVAD recipients. BACKGROUND: pVO2 is a cornerstone in the selection of patients for heart transplantation, but the prognostic power of pVO2 obtained in patients treated with a left ventricular assist device (LVAD) is unknown. METHODS: We collected data for pVO2 and outcomes in adult LVAD recipients in a retrospective, multicenter study and evaluated cutoff values for pVO2 including: 1) values above or below medians; 2) grouping patients in tertiles; and 3) pVO2 ≤14 ml/kg/min if the patient was not treated with beta-blockers (BB) or pVO2 ≤12 ml/kg/min if the patient was taking BB therapy. RESULTS: Nine centers contributed data from 450 patients. Patients were 53 ± 13 years of age; 78% were male; body mass index was 25 ± 5 kg/m2 with few comorbidities (stroke: 11%; diabetes: 18%; and peripheral artery disease: 4%). The cause of heart failure (HF) was most often nonischemic (66%). Devices included were the HeartMate II and 3 (Abbott); and Heartware ventricular assist devices Jarvik and Duraheart (Medtronic). The index CPET was performed at a median of 189 days (154-225 days) after LVAD implantation, and mean pVO2 was 14.1 ± 5 ml/kg/min (47% ± 14% of predicted value). Lower pVO2 values were strongly associated with poorer survival regardless of whether patients were analyzed for absolute pVO2 in ml/kg/min, pVO2 ≤12 BB/14 ml/kg/min, or as a percentage of predicted pVO2 values (P ≤ 0.001 for all). For patients with pVO2 >12 BB/14 and ventilation/carbon dioxide relationship (VE/VCO2) slope <35, the 1-year survival was 100%. CONCLUSIONS: Even after LVAD implantation, pVO2 has prognostic value, similar to HF patients not supported by mechanical circulatory support devices. (PROgnostic Value of Exercise Capacity Measured as Peak Oxygen Uptake [pVO2] in Recipients of Left Ventricular Assist Devices [PRO-VAD]; NCT04423562).

Determinants of Functional Capacity and Quality of Life After Implantation of a Durable Left Ventricular Assist Device.

Continuous-flow left ventricular assist devices (LVAD) are increasingly used as destination therapy in patients with end-stage heart failure and, with recent improvements in pump design, adverse event rates are decreasing. Implanted patients experience improved survival, quality of life (QoL) and functional capacity (FC). However, improvement in FC and QoL after implantation is not unequivocal, and this has implications for patient selection and preimplantation discussions with patients and relatives. This article identifies preimplantation predictors of lack of improvement in FC and QoL after continuous-flow LVAD implantation and discusses potential mechanisms, allowing for the identification of potential factors that can be modified. In particular, the pathophysiology behind insufficient improvement in peak oxygen uptake is discussed. Data are included from 40 studies, resulting in analysis of >700 exercise tests. Mean peak oxygen uptake was 13.4 ml/kg/min (equivalent to 48% of predicted value; 259 days after implantation, range 31-1,017 days) and mean 6-minute walk test distance was 370 m (182 days after implantation, range 43-543 days). Finally, the interplay between improvement in FC and QoL is discussed.

Comparative analysis of regional outcomes and adverse events after continuous-flow left ventricular assist device implantation: An IMACS analysis.

INTRODUCTION: Regional outcomes after implantation of continuous-flow left ventricular assist devices (LVADs) have not been described. We examined differences in patient selection, survival, and adverse events across 3 geographic regions of the world: the Americas, Asia-Pacific, and Europe. METHODS: Using data from The International Society for Heart and Lung Transplantation Mechanically Assisted Circulatory Support registry, all adult patients implanted with a continuous-flow LVADs were included in this International Society for Heart and Lung Transplantation Mechanically Assisted Circulatory Support analysis (n = 15,560), of whom, 9,988 (64%) received axial-flow devices and 5,572 (36%) received centrifugal-flow devices. RESULTS: There were significant interregional differences in the rate of implantation of patients aged >70 years (Americas: 14%, Asia-Pacific: 1%, Europe: 5%; p < 0.0001), morbidly obese (Americas: 5%, Asia-Pacific: 1%, Europe: 1%; p < 0.0001), male (Americas: 79%, Asia-Pacific: 77%, Europe: 85%; p < 0.0001), and implanted as destination therapy (Americas: 48%, Asia-Pacific: 4%, Europe: 22%; p < 0.0001). The rates of centrifugal pump usage varied by region (Americas: 30%, Asia-Pacific: 34%, Eu: 74%; p < 0.0001). Survival rates varied by region and the type of pump flow, with survival at 12 and 48 months (axial flow vs centrifugal flow) being 82% vs 82% and 52% vs 53 in Americas; 92% vs 86% and 83% vs 74% in Asia-Pacific; and 80% vs 75% and 69% vs 53% in Europe, respectively (regional survival p < 0.0001). CONCLUSION: There are marked global differences in LVAD recipient characteristics, device utilization, and post-operative care. These heterogeneities along with differences in patient management and transplantation rates may impact long-term survival. Regional differences in adverse event incidence warrant further investigation.

Predictors of Physical Capacity 6 Months After Implantation of a Full Magnetically Levitated Left Ventricular Assist Device: An Analysis From the ELEVATE Registry.

BACKGROUND: In patients with a continuous-flow left ventricular assist device, preimplant predictors of poor physical performance are not well-described. We aimed to identify predictors of inability to walk more than 300 m on 6-minute walk test (6MWT) 6 months after HeartMate 3 implantation. METHODS AND RESULTS: Using data from the European Registry of Patients Implanted With a Full Magnetically Levitated LVAD, patients with available 6MWT at 6 months after implantation were included (N = 194) and grouped according to 6MWT distance (6MWD) of >300 m (n = 150) or 6MWD of <300 m (n = 44). Patients walking <300 m were older (60 ± 10 vs 52 ± 12 years; P < .001), more often New York Heart Association functional class IV (63% vs 42%; P = .03), and more often had type 2 diabetes (43% vs 17%; P < .001) at implantation. Atrial fibrillation was seen in 57% in those with a 6MWT of <300 m vs 31% in those walking longer (P < .002). Further, hemoglobin and estimated glomerular filtration rate was lower in those walking <300 m (both P < .01). In multivariable regression analysis, independent predictors of a 6MWD of <300 m were: atrial fibrillation (odds ratio [OR], 3.22; 95% confidence interval [CI], 1.12-8.67), older age (OR for 10-year increment, 2.81; 95% CI, 1.55-5.07), New York Heart Association functional class IV (OR, 3.37; 95% CI, 1.27-8.98), and Interagency Registry for Mechanically Assisted Circulatory Support profile 1 or 2 (OR, 6.53; 95% CI, 1.92-22.19). CONCLUSIONS: Six months after HeartMate 3 implantation, 77% of patients walked >300 meters in 6 minutes. Apart from age and measures of heart failure severity, atrial fibrillation at implantation is an independent predictor of low 6MWD at 6 months after implantation.

Effect of Heart Rate Reserve on Exercise Capacity in Patients Treated with a Continuous Left Ventricular Assist Device.

We hypothesized that an inadequate increase in heart rate (HR) during exercise was associated with low peak oxygen uptake (VO2 peak) seen in left ventricular assist device (LVAD) recipients and aimed to analyze the potential relation between HR and VO2 peak and use of drugs with negative chronotropic effect. Sixty-eight LVAD recipients (44 Heartmate 2 and 24 HeartWare Ventricular Assist Device) with support duration >1 month and a VO2 peak were included from two centers. Patients were 57 ± 13 years at time of VO2 peak and LVAD support duration was 483 ± 545 days. Peak oxygen uptake was 12 ± 4 ml/kg/min (40% ± 13% of predicted). Heart rate reserve (HRR = maximal HR - resting HR) was 59 ± 22 min (75% ± 15% of predicted for age, %HRR) and was significantly associated with VO2 peak (r = 0.244, p = 0.045). Predicted heart rate reserve was associated with %Predicted VO2 peak (P = 0.011). Chronotropic incompetence (CI) was observed in 44% and VO2 peak was clearly lower in patients with CI (10 ± 2.7 vs. 13 ± 4.6 ml/kg/min, p = 0.005). Beta-blockers (BB) were prescribed to 85% and adjusting for being on target BB-dose did not affect the correlation between %predicted VO2 peak and %HRR (r = 0.33, p = 0.024). In conclusion, almost half of LVAD recipients suffer from CI which is associated with lower VO2 peak. This relation did not seem to be affected by BB therapy.

Computed Tomography-Estimated Right Ventricular Function and Exercise Capacity in Patients with Continuous-Flow Left Ventricular Assist Devices.

Using four-dimensional (4D) cardiac computed tomography (CCT) scans at rest and immediately after exercise, we examined the right heart chamber sizes and systolic function and its association with exercise capacity in left ventricular assist device (LVAD) recipients. Fifteen patients with HeartMate (HM) II or 3 underwent echocardiography and maximal cardiopulmonary exercise test. Subsequently, contrast-enhanced CCT scans were performed at rest and immediately after two minutes of supine 25 Watt ergometer bike exercise. Patients were (60 ± 12 years of age) 377 ± 347 days postimplant. Peak oxygen uptake (pVO2) was 15 ± 5 ml/kg/min. LV ejection fraction measured by echocardiography was 15 ± 9%. Pump speed was 9500 ± 258 in HM II and 5518 ± 388 rpm in HM 3 recipients. Resting right atrial ejection fraction (RAEF) was 18 ± 9%, and right ventricular ejection fraction (RVEF) was 36 ± 8%. During stress, RAEF was 19 ± 10%, and RVEF was 37 ± 8%. RAEF and RVEF did not correlate significantly with pVO2 at rest or during stress. Resting-RAEF and stress RAEF correlated significantly: r = 0.87, p < 0.01 as did resting RVEF and stress RVEF: r = 0.76, p < 0.01. In conclusion, resting-EF predicted stress-EF for both RA and RV in patients with an LVAD. Neither RVEF nor RAEF correlated with pVO2.

Ergospirometry with concurrent fibre optic laryngoscopy: a randomised crossover study.

Background: Patients suffering from exercise-induced laryngeal obstruction (EILO) are subjected to several exhausting tests. We aimed to assess the feasibility of using a single test to obtain diagnostic measurements for maximum oxygen uptake (VO2max) and exercise-induced laryngeal obstruction (EILO). Methods: Patients referred to the outpatient respiratory clinic at the University Hospital of Bispebjerg, Copenhagen with exercise-induced dyspnoea were evaluated for inclusion over 13 months. Eligible patients were aged 18-43 years, had a known EILO diagnosis (moderate or severe) and were inactive (self-reported activity) with less than 3 hours activity per week. In randomised order, all participants (n = 11) underwent three tests: a VO2max test with and without concurrent laryngoscopy. VO2max and EILO values from the two testing methods were compared. Findings: There was no difference in VO2max measured by ergospirometry with and without simultaneous continuous laryngoscopy during exercise (CLE) testing (mean difference -22 ml O2ï½¥min-1; 95% CI -125 to 81 ml O2ï½¥min-1; P = 0.647). EILO scores obtained during the CLE testing on the treadmill versus CLE testing on the ergometer bike revealed identical supraglottic scores in nine of the 11 participants (82%) with substantial agreement between the two types of test (x = 0.71). Glottic scores were identical in six of the 11 (55%), showing moderate agreement between test types (x = 0.38). Conclusions: Based on our findings in inactive individuals, ergospirometry with laryngoscopy is feasible and well tolerated, yielding measurements for maximal oxygen uptake comparable to those of standard bike ergospirometry. Likewise, measurements of supraglottic EILO are comparable to those of the standard treadmill CLE test.

Effect of everolimus initiation and early calcineurin inhibitor withdrawal on myocardial FOXP3+ regulatory T cells in heart transplantation.

BACKGROUND: Through immunosuppression CD4+FoxP3+ regulatory T-cells (Tregs) play an indispensable role in allograft rejection. Post-HTx treatment with everolimus is associated with slower progression of cardiac allograft vasculopathy (CAV) - chronic rejection - than CNI based therapy. We hypothesized treatment with everolimus reduced the risk of CAV by modulating myocardial FoxP3 levels. METHODS: 15 patients from the Schedule trial comparing everolimus, MMF, steroid and early CNI (Everolimus, n=8) withdrawal to conventional CNI based immunosuppression (Controls, n=7) after de novo HTx were included and FoxP3+ cells were quantified in 56 endomyocardial biopsies, and compared in the two patient groups. CAV was evaluated invasively using coronary intravascular ultrasound (IVUS). RESULTS: Baseline FoxP3 biopsy levels were similar in the two groups. The Everolimus group showed a significant increase in Foxp3 densities from baseline to time of one-year follow-up (median (IQR)=4.8×10(-7)(20.4) Tregs/µm(2), P=0.046) while Controls showed no significant change (median (IQR)=3.1×10(-7)(6.5) Tregs/µm(2), P=0.116). At 1-month follow-up FoxP3 densities correlated with the observed change in TAV from baseline to time of 1-year follow-up (r=0.641, P=0.034). FoxP3 densities at 1-week predicted acute cellular rejection (ACR) levels at 1month (P=0.026). No other correlations with ACR were found. CONCLUSION: Everolimus treatment combined with early CNI elimination is associated with increased densities of Tregs 12-months post-HTx compared to patients receiving CNI based regimen. Furthermore, the density of myocardial FoxP3+ cells early after transplantation appears to predict at least one measure of CAV burden after one year.