scholarly journals Reduced NT-proBNP threshold for risk prediction in high-risk elderly with subclinical heart failure: support from cardiopulmonary exercise testing

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
E Potter ◽  
M Woessner ◽  
T.H Marwick

Abstract Background Subclinical heart failure (HF) is divided into Stage A and B (SAHF and SBHF) depending on structural or functional cardiac abnormalities. However, risk of HF progression is not solely dependent on echocardiographic abnormalities. Data on oxygen consumption (VO2) and other prognostic cardiopulmonary exercise test (CPET) markers in subclinical HF, particularly in the elderly, is lacking. VO2 may refine risk prediction and provide pathological insight in subclinical HF. Methods Asymptomatic individuals were recruited through primary care if they were ≥65 years with ≥1 non-ischaemic risk factor for HF. Clinical evaluation determined risk profile, biometrics and NT-proBNP. Treadmill CPET was undertaken with a modified Bruce protocol. Low V02 was defined as ≤20th percentile of age and gender specific VO2 in healthy individuals. SBHF defined as systolic (global longitudinal strain, GLS ≤16%), diastolic (E/e' ≥15, E/e' >10 with left atrial enlargement or impaired relaxation with other changes or left ventricular (LV) hypertrophy (LV mass index >95 g/m2 in women or >115 g/m2 in men). Results Of the 91 included individuals (age 71±4 years, 53% female), 46 (51%) had SBHF, average NT-proBNP was 60pg/ml (26–99mg/ml) and did not differ by HF stage (59 [26–85] pg/ml vs. 60 [30–99] pg/ml for Stage A vs. B respectively, p=0.94). Average peak VO2 was 19.8 (16–22.6) ml/kg/min and was low in 71 (78%). VO2 did not differ by HF stage (19.9 [17.7–22.4] ml/kg/min vs. 19.7 [16–22.8] ml/kg/min for SAHF vs. SBHF respectively, p=0.62). NT-proBNP was significantly higher in those with abnormal VO2 (66 [34–110] pg/ml vs 31 [20–70] pg/ml, p=0.016). Within each HF stage, low VO2 was associated with higher NT-proBNP (Figure). Of those with NT-proBNP >100pg/ml, 95% (22/23) had low VO2 compared with 72% of those ≤100pg/ml, p=0.02 (non-signifcant for 125pg/ml cut-off). No associations were found between SBHF or individual echo abnormalities and VO2. In logistic regression analysis NT-proBNP was a significant univariable predictor of low VO2 and remained significant after adjustment for other significant univariables (BMI) (OR 1.02 [95% CI 1.0001–1.03], p=0.048). Conclusion Low VO2 identifies a high-risk cardiac phenotype within subclinical HF stages, but is not necessarily associated with LV dysfunction. Levels of NT-proBNP beneath the cut-off used for HF exclusion may assist risk stratification in this population. NT-proBNP by VO2 in subclinical HF Funding Acknowledgement Type of funding source: Public Institution(s). Main funding source(s): Dr E Potter is supported by a PhD Scholarship from Monash University, Melbourne, Australia

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
D.X Avila ◽  
R.C Vivacqua ◽  
S Serra ◽  
M.W Montera ◽  
E Tinoco ◽  
...  

Abstract Introduction Cardiopulmonary exercise testing (CPET) has become an important clinical tool to predict outcome in patients with chronic heart failure (CHF) and help to select candidates for heart transplantation (HTx) or left ventricular assist devices (LVAD). Purpose To evaluate CPET measurements in advanced CHF patients that are being considered for HTx or LVAD and its association to early mortality regardless of the performed procedure. Methods Maximum intensity CPET was performed on a treadmil and ramp protocol in 65 patients with patients with CHF and reduced ejection fraction, NYHA functional classes III and IV between 2012 and 2018. Measurements derived from CPET were the following: peak V'O2, VO2 at the anaerobic threshold (AT), percentage of the VO2 of the anaerobic threshold in relation to the peak, the VE/VCO2 slope, maximum heart rate (HR), respiratory quotient (R), oxygen kinetics, circulatory power (CP), the recovery HR in the first minute and the oxygen uptake efficiency slope (OUES) and the relation (VE/VCO2 slope)/VO2 peak. Results Seventy-four percent were male. Mean age of 67±12 years. Amost half (47%) had ischemic etiology. There were no complications related to CPET. Ten patients were transplanted, six had an intracorporeal LVAD implanted and the reminder (49 patients) were kept in supervised physical rehabilitation program. There were 11 deaths, 2 in HTx, 2 in LVAD, 7 in the rehabilitation group. Mean follow-up among the survivors was 43 months ± 40.6 and it was 12.1±10.3 months in those who died. CPET derived measurements between survivors and non-survivors were as follows: V'O2 peak (mL kg–1 min–1): 12.6±4.6 and 8.6±2.7 (p=0.002); the VO2 AT (mL kg–1 min–1): 9.9±3.3 and 6.1±3.0 (p=0.002); VE/VCO2 slope: 34.2±12.1 and 68.1±68.7 (p=0.0003); R peak: 1.1±0.2 and 1.0±0.1 (p=0.009); t1/2, in seconds: 135.8±47.9 and 170.1±82.0 (p=0.03); HR at the first minute 16.6±13 and 7±5 (p=0.009); OUES (L min–1): 1.1±0.4 and 0.9±0.3 (p=0.04) and CP [(ml O2 kg–1 min–1) mmHg] 1.516.2±689. 3 and 960.6±363.6 (p=0.005). and the relation (VE/VCO2 slope)/V'O2 peak were 3.2±2.0 and 11.4±19.5 (p=0.001), respectively. Conclusion The predisposition to early death could be stratified by V'O2 peak, VO2 of the ventilatory threshold, VE/VCO2 slope, t1/2, recovery HR, OUES, CP, and by the relation (VE/VCO2 slope)/V'O2 peak. Funding Acknowledgement Type of funding source: Private hospital(s). Main funding source(s): own financing


2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
S Hui ◽  
A Sharma ◽  
K Docherty ◽  
J.J.V McMurray ◽  
B Pitt ◽  
...  

Abstract Background Sudden cardiac death (SCD) is responsible for 20–40% of mortality following acute myocardial infarction (AMI). The risk of SCD is even higher among patients with AMI complicated by heart failure (HF) (either clinically apparent HF or left ventricular dysfunction). The temporal relationship between an AMI complicated by HF and subsequent SCD and the association of non-fatal cardiovascular (CV) events following AMI with SCD has yet to be described. Purpose Among patients with AMI complicated by HF, we evaluated the probability and temporal association of subsequent non-fatal cardiovascular (CV) events (HF hospitalization, recurrent MI, or stroke) and SCD. Methods The High-Risk Myocardial Infarction (HRMI) database contains 28,771 patients with signs of HF or reduced LV ejection fraction (<40%) after AMI. Among patients with an AMI complicated by HF, we used adjudicated cause of death from the HRMI Database to identify: 1) the temporal distribution of SCD among patients following an index AMI; 2) the probability of having SCD following a non-fatal CV event following the index AMI. Results Median follow-up was 1.9 years. Mean age was 65.0±11.5 years and 70% were male. The incidence of CV death was 7.9 per 100 patient-year [py] and for SCD was 3.1 per 100py (40% of CV deaths). SCD rates were highest in the early period (<90 days) after AMI and decreased over time. Recurrent MI preceded 9.6% of SCD after a median time of 145 days; HF hospitalization preceded 17.0% of SCD after a median 144 days; and stroke preceded 2.7% of SCD after a median of 138 days (vs. non-sudden CV death: MI 46.6% at 1 days, HF hospitalization: 30.9% at 67 days, stroke 12.9% at 9 days). The incidence of SCD preceded by HF hospitalization was significantly higher than SCD without preceding HF hospitalization. Conclusion Among patients with AMI complicated by HF, SCD predominantly occurred in the early “high-risk” period after AMI; SCD rates decreased afterwards. Patients with non-fatal HF hospitalizations during follow-up may have a higher subsequent SCD risk. Preventing HF onset after MI may help decreasing SCD. Proportion of sudden cardiac death Funding Acknowledgement Type of funding source: Public Institution(s). Main funding source(s): Lucien Award, McGill University


2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
T Chwyczko ◽  
L Zalucka ◽  
E Smolis-Bak ◽  
I Kowalik ◽  
E Noszczak ◽  
...  

Abstract Background Rehabilitation after LVAD implantation is increasingly used. We developed the novel method of comprehensive rehabilitation starting directly after LVAD implantation. Study group 21 recent LVAD (15 Heart Mate III, 6 HeartWare) recipients (56.2±11.7 yrs, 100% men) were included to 5-week rehabilitation program, which included supervised endurance training on cycloergometer (5 times per week), resistance training, general fitness exercises with elements of equivalent and coordination exercises (every day). 6-minute walking test (6MWT), cardiopulmonary exercise test (CPET) and prognostic biomarkers: NT-proBNP, Galectin-3 and ST2 were investigated at the beginning and at the end of rehabilitation program. Results See Table 1. At the end of rehabilitation program, significant increase in 6MWT distance, maximum workload, peak VO2 and upward shift of anaerobic threshold in CPET were observed in all patients. Significant reductions of NTproBNP, ST2 and galectin-3 levels were observed. There were no major adverse events during rehabilitaton. Conclusions Comprehensive novel rehabilitation in LVAD recipients is safe and results in significant improvement of 6-minutes walking test distance and cardiopulmonary exercise test results. Moreover, this novel rehabilitation program reduces levels of prognostic biomarkers of heart failure: NT-proBNP, Galectin-3 and ST2. Funding Acknowledgement Type of funding source: Public grant(s) – National budget only. Main funding source(s): National Center for Research and Development - STRATEGMED II project


2021 ◽  
Vol 28 (Supplement_1) ◽  
Author(s):  
P Garcia Bras ◽  
A Valentim Goncalves ◽  
J Reis ◽  
T Pereira Da Silva ◽  
R Ilhao Moreira ◽  
...  

Abstract Funding Acknowledgements Type of funding sources: None. Introduction Cardiopulmonary exercise testing (CPET) is used for risk stratification in patients with chronic heart failure (CHF). However, there is a lack of information regarding CPET prognostic power in patients under new HF therapies such as sacubitril/valsartan, Mitraclip, IV iron or SGLT2 inhibitors. The aim of this study was to evaluate the prognostic value of CPET parameters in a contemporary subset of patients with optimal medical and device therapy for CHF. Methods Retrospective evaluation of patients with CHF submitted to CPET in a tertiary center. Patients were followed up for 24 months for the composite endpoint of cardiac death, urgent heart transplantation or left ventricular assist device. CPET parameters, including peak oxygen consumption (pVO2) and VE/VCO2 slope, were analysed and their predictive power was measured. HF events were stratified according to cut-off values defined by the International Society for Heart and Lung Transplantation (ISHLT) guidelines: pVO2 of ≤12 mL/Kg/min and VE/VCO2 slope of >35. Results CPET was performed in 204 patients, from 2014 to 2018. Mean age was 59 ± 13 years, 83% male, with a mean left ventricular ejection fraction of 33 ± 8%, and a mean Heart Failure Survival Score of 8.6 ± 1.3. The discriminative power of CPET parameters is displayed in the Table. In patients with pVO2 ≤12 mL/Kg/min, the composite endpoint occurred in 18% of patients. A pVO2 value of ≤12 mL/Kg/min had a positive predictive power of 18% while pVO2 >12 had a negative predictive power of 93%. Regarding VE/VCO2 slope >35, the composite endpoint occurred in 13% of patients. A VE/VCO2 slope value of >35 had a positive predictive power of 13% while VE/VCO2 slope <35 had a negative predictive power or 94%. Conclusion Using ISHLT guideline cut-off values for advanced HF therapies patient selection, there was a reduced number of HF events (<20%) at 24 months in patients under optimal CHF therapy. While pVO2 and VE/VCO2 slope are still valuable parameters in risk stratification, redefining cut-off values may be necessary in a modern HF population. Discriminative power of CPET parameters Parameters HR; 95% CI AUC p-value Peak VO2 0.824 (0.728-0.934) 0.781 0.001 Percent of predicted pVO2 0.942 (0.907-0.978) 0.774 0.002 VE/VCO2 slope 1.068 (1.031-1.106) 0.756 0.008 Cardiorespiratory optimal point 1.118 (1.053-1.188) 0.746 0.004 PETCO2 maximum exercise 0.854 (0.768-0.950) 0.775 0.003 Ventilatory Power 0.358 (0.176-0.728) 0.796 0.002 HR Hazard ratio, AUC: Area under the curve, PETCO2: end-tidal CO2 pressure


2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Christine Sailer ◽  
Hannah Edelmann ◽  
Cullen Buchanan ◽  
Pedro Giro ◽  
Matthew Babcock ◽  
...  

Background: Continuous-flow (CF) left ventricular assist devices (LVADs) improve outcomes for patients with advanced heart failure (HF). However, the lack of a physiological pulse predisposes to side-effects including uncontrolled blood pressure (BP), and there are little data regarding the impact of CF-LVADs on BP regulation. Methods: Twelve patients (10 males, 60±11 years) with advanced heart failure completed hemodynamic assessment 2.7±4.1 months before, and 4.3±1.3 months following CF-LVAD implantation. Heart rate and systolic BP via arterial catheterization were monitored during Valsalva maneuver, spontaneous breathing, and a 0.05 Hz repetitive squat-stand maneuver to characterize cardiac baroreceptor sensitivity. Plasma norepinephrine levels were assessed during head-up tilt at supine, 30 o and 60 o . Heart rate and BP were monitored during cardiopulmonary exercise testing. Results: Cardiac baroreceptor sensitivity, determined by Valsalva as well as Fourier transformation and transfer function gain of Heart rate and systolic BP during spontaneous breathing and squat-stand maneuver, was impaired before and following LVAD implantation. Norepinephrine levels were markedly elevated pre-LVAD and improved—but remained elevated post-LVAD (supine norepinephrine pre-LVAD versus post-LVAD: 654±437 versus 323±164 pg/mL). BP increased during cardiopulmonary exercise testing post-LVAD, but the magnitude of change was modest and comparable to the changes observed during the pre-LVAD cardiopulmonary exercise testing. Conclusions: Among patients with advanced heart failure with reduced ejection fraction, CF-LVAD implantation is associated with modest improvements in autonomic tone, but persistent reductions in cardiac baroreceptor sensitivity. Exercise-induced increases in BP are blunted. These findings shed new light on mechanisms for adverse events such as stroke, and persistent reductions in functional capacity, among patients supported by CF-LVADs. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT03078972.


Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Elizabeth L Potter ◽  
Mary N Woessner ◽  
Christopher Neil ◽  
Thomas H Marwick ◽  
Erin Howden

Introduction: Peak oxygen utilisation (VO 2 ) and ventilatory efficiency (VE/VCO 2 slope) provide strong prognostic information in symptomatic heart failure (HF). Transition from subclinical to symptomatic HF is poorly understood. Cardiopulmonary exercise testing (CPET) in subclinical HF may advance risk profiling. Hypothesis: HF risk factors are associated with metabolic and ventilatory abnormalities that may serve as risk markers. Methods: Sedentary subjects (n=81; 67 (66-72) years; 65% female; BMI 29.9[26.6-33.9] kg/m 2 ) with ≥1 HF risk factors (Stage A HF, SAHF) without pulmonary disease and healthy sedentary subjects (controls, n=21; 70 (67-73) years; 52% female; BMI 25.1 [24-25.9] kg/m 2 ) underwent treadmill CPET to determine peak VO 2 , ventilatory threshold (VT, V-slope method) and VE/VCO 2 slope (linear regression). Global longitudinal strain≤16%, diastolic dysfunction or left ventricular hypertrophy defined subclinical left ventricular dysfunction (LVD). Results: LVD was present in 41 (51%) with SAHF. CPET parameters did not differ by presence of LVD. There were no differences in peak RER or VT (% peak VO2) between controls and SAHF. VO 2 peak was higher in controls vs. SAHF (22.1±4.6 vs. 19.9±4.6ml/kg/min, p=0.047). VE/VCO 2 slope was markedly steeper in SAHF vs. controls (40.2±6.2 vs. 29.3±6.1, p<0.001) (Figure). VE/VCO 2 slope was >34 (prognostic in symptomatic HF) in 83% vs. 19% for SAHF vs. controls (p<0.001). BMI was the only independent predictor (β 0.45 (0.19-0.72, p=0.001) (r 2 0.16) of VE/VCO 2 slope (SBP and heart rate reserve were not). BMI was not associated with increment in respiratory rate or tidal volume (β0.18(-0.07-0.42) and β3.9 (-10.8-18.7)). Conclusions: Cardiorespiratory exercise parameters do not differ in SAHF by presence of LVD. Ventilatory inefficiency is pronounced in SAHF compared with healthy controls suggesting it may be a risk marker, but prognostic significance is unknown.


2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
S Bots ◽  
N.C Onland-Moret ◽  
I.I Tulevski ◽  
G.A Somsen ◽  
H.M Den Ruijter

Abstract Background Heart failure (HF) guidelines recommend equal target doses for women and men. Recently, these recommendations have been challenged as research suggested that women with HF with reduced Ejection Fraction (HFrEF) may reach optimal treatment effect at half of the guideline-recommended dose while men may require the full dose. However, it is unclear how often women and men reach guideline-recommended target doses in daily practice. Purpose To evaluate whether women and men with HF reach guideline-recommended target doses for Angiotensin-converting enzyme inhibitors (ACEI)/angiotensin II receptor blocker (ARB), β-blockers (BB) and mineralocorticoid receptor antagonists (MRA) in daily practice. Methods We extracted data from 13 outpatient cardiology clinics for all individuals diagnosed with HF within 14 days leading up to their visit who were prescribed at least one guideline-recommended HF medication. HF was defined based on a combination of the cardiologist's diagnosis and left ventricular systolic or diastolic dysfunction determined during echocardiography. Guideline-recommended medication groups and target doses were taken from the 2016 ESC HF guidelines or from literature for medications not mentioned in the guidelines. To enable comparison between medications and medication groups, daily dose was converted to percentage of target dose. Mean change in percentage of target dose over consecutive medication prescriptions was modelled for men and women using natural cubic splines. Results We included 1254 patients with HF (48% women). Women were on average older at diagnosis (71 vs 67 years) and more often had hypertension (54.9 vs 44.3%), but less often had diabetes mellitus (13.5 vs 19.4%), a history of coronary heart disease (7.8 vs 19.6%,) or past cardiovascular interventions (8.7 vs 23.0%) than men. In total, 1069 patients were prescribed an ACEI/ARB (46% women), 920 a BB (48% women) and 243 an MRA (43% women). Women were more often prescribed only one medication than men (39.6 vs 33.2%, p=0.014). Approximately 14% of first prescriptions for all medications were at 100% of target dose or higher for both women and men, with the majority of prescriptions being either at 1–49% of target dose (47.2 vs 45.5%, respectively) or 50–99% of target dose (39.1 vs 40.8%, respectively). The natural cubic splines showed that this distribution did not change over consecutive drug prescriptions in either women or men. Only MRA prescriptions for men showed an upward trend and reached 100% of target dose. Conclusion In daily practice, both women and men were unlikely to reach guideline-recommended target doses for both ACEI/ARBs and BBs. For MRAs, women were less likely to reach target dose than men. Optimal dosing in HF is difficult for both sexes, but in light of recent evidence, the challenge in daily practice seems to lie more in undertreatment of men than overtreatment of women. Figure 1 (women in red, men in blue) Funding Acknowledgement Type of funding source: Public Institution(s). Main funding source(s): ZonMw


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