Abstract 14036: An Algorithm to Guide Prognosis Based on the Combination of Peak VO 2 and V E -VCO 2 slope in Patients with HFrEF: The Henry Ford HospITal CardioPulmonary EXercise Testing (FIT-CPX) Project

Circulation ◽  
2014 ◽  
Vol 130 (suppl_2) ◽  
Author(s):  
Clinton A Brawner ◽  
Ali Shafiq ◽  
Heather A Aldred ◽  
Raakesh Hassan ◽  
Stephanie Vasko ◽  
...  

Many studies have reported the prognostic significance of peak oxygen consumption (VO 2 ) and V E -VCO 2 slope in patients with heart failure (HF). However, there are limited data stratifying risk based on a combination of these measures and how to best use them. Purpose: Describe 1 and 3-y event rates for the composite endpoint of mortality, left ventricular assist device (LVAD), or cardiac transplant (CT) based on the combined evaluation of peak VO 2 and V E -VCO 2 slope in patients with HF with reduced ejection fraction (≤ 40%; HFrEF). Methods: Patients (n= 1,116; 33% female; age= 54 ± 13 y) with a cardiopulmonary exercise test between 1997 and 2010 and confirmed HFrEF were identified. Endpoint data was obtained through 2011. Patients were grouped based on peak VO 2 (< 12, 12 to18, and > 18 mL/kg/min) and (V E -VCO 2 slope ≥ 34 or < 34). Cumulative events were identified from life tables. Cox regression with adjustment for age, gender, ejection fraction, and beta-blocker therapy was used to calculate the hazard ratio for V E -VCO 2 slope ≥ 34 within each peak VO 2 group. Results: The 1 and 3-y event rates are shown in the Table. Among patients with a peak VO 2 < 12, 1 and 3-y events were 23% and 44%, respectively. Within this group, V E -VCO 2 slope ≥ 34 represented more than twice the risk at both 1 y (HR 2.42, 95% CI 1.09, 5.38) and 3 y (HR 2.32, 95% CI 1.33, 4.05). Among patients with a peak VO 2 12 to 18, 1 and 3-y events were 14% and 30%, respectively. Within this group, a V E -VCO 2 slope ≥ 34 was associated with increased risk at both 1 y (HR 1.80, 95% CI 1.13, 2.87) and 3 y (HR 1.80, 95% CI 1.30, 2.50). Among patients with peak VO 2 > 18, 1 and 3-y events were 2% and 10%, respectively, and V E -VCO 2 slope was not statistically associated with increased risk. Conclusion: Among patients with a peak VO 2 ≤ 18, V E -VCO 2 slope ≥ 34 further refines the risk for a composite endpoint of mortality, LVAD, or CT at both 1 and 3 y.

Circulation ◽  
2014 ◽  
Vol 130 (suppl_2) ◽  
Author(s):  
Clinton A Brawner ◽  
Ali Shafiq ◽  
Heather A Aldred ◽  
Raakesh Hassan ◽  
Stephanie Vasko ◽  
...  

The prognostic utility of cardiopulmonary exercise testing (CPX) in patients with heart failure and reduced ejection fraction (HFrEF) has received much attention. However, there are limited data on the value of CPX in patients with HF and preserved EF (HFpEF). Purpose: Among patients with HFpEF, describe the association between select CPX measures and prognosis for the composite endpoint of mortality, left ventricular assist device (LVAD), or cardiac transplant (CT). Methods: Patients with a CPX between 1997 and 2010 and confirmed HFrEF (EF ≤ 40%; n= 1,201) or HFpEF (EF ≥ 50%; n= 192) were identified. Patients with HFpEF (n= 189, age= 54 ± 14 y, 43% female, EF = 56 ± 5%) were matched (propensity score) to patients with HFrEF (n= 189, age= 54 ± 13 y, 43% female, EF = 22 ± 9%) based on age, gender, history of coronary artery disease, and body mass index. Endpoint data was obtained through 2011. The association between select CPX measures and the endpoint was assessed using Cox regression with adjustment for age, gender, EF, and beta-blocker therapy. Results: There were 53 events (28%; median follow-up = 5.1 y) among the HFpEF group and 88 events (47%; median follow-up = 3.6 y) among the HFrEF group. Results from the Cox regression analyses are shown in the Table. Percent predicted peak VO 2 was one of the best predictors of the endpoint in both HFpEF and HFrEF with similar hazard ratios. Although significantly related to the endpoint among HFrEF, V E -VCO 2 slope and peak P ET CO 2 were not significant among HFpEF. Conclusions: These data support the use of % predicted peak VO 2 to risk stratify patients with HFpEF and suggest that the prognostic utility of some CPX measures developed in HFrEF may not be relevant in HFpEF. Additional research is needed to define the association between CPX measures and prognosis specifically for patients with HFpEF.


Circulation ◽  
2014 ◽  
Vol 130 (suppl_2) ◽  
Author(s):  
Ali Shafiq ◽  
Clinton A Brawner ◽  
Heather E Aldred ◽  
Raakesh Hassan ◽  
Stepahanie Vasko ◽  
...  

Introduction: Numerous metrics derived from the cardiopulmonary exercise test (CPX) are associated with outcomes among patients with heart failure with reduced ejection fraction (HFrEF). However few studies have examined the independent prognostic value of all variables assessed simultaneously. Purpose: Retrospective analysis to describe the relationship between all CPX measures and the composite outcome of mortality, left ventricular assist device (LVAD), or cardiac transplant (CT). Methods: Patients (n= 1,201; 33% female; age= 55 ± 13 y) with a CPX between 1997 and 2010 and confirmed HFrEF (ejection fraction [EF] < 40%) were identified. Death data through 2011 was obtained from the National Death Index. The association with the composite endpoint was evaluated separately for 30 CPX measures with adjustment for age, gender, EF, and beta-blocker therapy using Cox regression. Forward stepwise Cox regression was performed to identify which of the CPX variables contribute the most to outcome prediction. Results: During a median follow-up of 3.75 years there were 576 (48%) events. When tested separately, nearly all CPX variables (except heart rate reserve/metabolic reserve and peak respiratory exchange ratio) were associated (p<0.05) with the composite endpoint. The top 5 predictors are shown in the Table. Stepwise Cox regression revealed that only % predicted peak oxygen uptake (VO 2 , Wald= 76.1), ventilatory power (peak systolic blood pressure/V E -VCO 2 slope, Wald= 58.0), and EF (Wald= 27.0) independently predicted outcomes. Conclusion: When considering all variables measured during a CPX test, % predicted peak VO 2 was the variable with the strongest independent association to outcomes in this cohort of patients with HFrEF. The % predicted peak VO 2 may represent a key variable in determining when to consider a patient for an LVAD or CT.


2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
B.M.L Rocha ◽  
G.J Lopes Da Cunha ◽  
P.M.D Lopes ◽  
P.N Freitas ◽  
F Gama ◽  
...  

Abstract Background Cardiopulmonary exercise testing (CPET) is recommended in the evaluation of selected patients with Heart Failure (HF). Notwithstanding, its prognostic significance has mainly been ascertained in those with left ventricular ejection fraction (LVEF) &lt;40% (i.e., HFrEF). The main goal of our study was to assess the role of CPET in risk stratification of HF with mid-range (40–49%) LVEF (i.e., HFmrEF) compared to HFrEF. Methods We conducted a single-center retrospective study of consecutive patients with HF and LVEF &lt;50% who underwent CPET from 2003–2018. The primary composite endpoint of death, heart transplant or HF hospitalization was assessed. Results Overall, 404 HF patients (mean age 57±11 years, 78.2% male, 55.4% ischemic HF) were included, of whom 321 (79.5%) had HFrEF and 83 (20.5%) HFmrEF. Compared to the former, those with HFmrEF had a significantly higher mean peak oxygen uptake (pVO2) (20.2±6.1 vs 16.1±5.0 mL/kg/min; p&lt;0.001), lower median minute ventilation/carbon dioxide production (VE/VCO2) [35.0 (IQR: 29.1–41.2) vs 39.0 (IQR: 32.0–47.0); p=0.002) and fewer patients with exercise oscillatory ventilation (EOV) (22.0 vs 46.3%; p&lt;0.001). Over a median follow-up of 28.7 (IQR: 13.0–92.3) months, 117 (28.9%) patients died, 53 (13.1%) underwent heart transplantation, and 134 (33.2%) had at least one HF hospitalization. In both HFmrEF and HFrEF, pVO2 &lt;12 mL/kg/min, VE/VCO2 &gt;35 and EOV identified patients at higher risk for events (all p&lt;0.05). In Cox regression multivariate analysis, pVO2 was predictive of the primary endpoint in both HFmrEF and HFrEF (HR per +1 mL/kg/min: 0.81; CI: 0.72–0.92; p=0.001; and HR per +1 mL/kg/min: 0.92; CI: 0.87–0.97; p=0.004), as was EOV (HR: 4.79; CI: 1.41–16.39; p=0.012; and HR: 2.15; CI: 1.51–3.07; p&lt;0.001). VE/VCO2, on the other hand, was predictive of events in HFrEF but not in HFmrEF (HR per unit: 1.03; CI: 1.02–1.05; p&lt;0.001; and HR per unit: 0.99; CI: 0.95–1.03; p=0.512, respectively). ROC curve analysis demonstrated that a pVO2 &gt;16.7 and &gt;15.8 mL/kg/min more accurately identified patients at lower risk for the primary endpoint (NPV: 91.2 and 60.5% for HFmrEF and HFrEF, respectively; both p&lt;0.001). Conclusions CPET is a useful tool in HFmrEF. Both pVO2 and EOV independently predicted the primary endpoint in HFmrEF and HFrEF, contrasting with VE/VCO2, which remained predictive only in latter group. Our findings strengthen the prognostic role of CPET in HF with either reduced or mid-range LVEF. Funding Acknowledgement Type of funding source: None


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 &gt;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 &gt;12 had a negative predictive power of 93%. Regarding VE/VCO2 slope &gt;35, the composite endpoint occurred in 13% of patients. A VE/VCO2 slope value of &gt;35 had a positive predictive power of 13% while VE/VCO2 slope &lt;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 (&lt;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


Circulation ◽  
2014 ◽  
Vol 130 (suppl_2) ◽  
Author(s):  
Greta Generati ◽  
Francesco Bandera ◽  
Marta Pellegrino ◽  
Valentina Labate ◽  
Eleonora Alfonzetti ◽  
...  

Background: In heart failure (HF) patients the severity of mitral regurgitation (MR) at rest has a well established prognostic value and its increase during exercise further adds to an increased risk. Our goal was to define the relationship between the degree of exercise MR severity with cardiopulmonary and echocardiographic related phenotypes in a cohort of HF patients. Methods: 71 HF reduced ejection fraction patients (mean age 67±11; male 72%; ischemic etiology 61%; NYHA class I, II, III and IV 13%, 36%, 39% and 12%, mean ejection fraction 33±9%) underwent cardiopulmonary exercise test (CPET) on tiltable cycle-ergometer combined with echocardiography at rest and during exercise. The population was divided into two groups according to the degree of functional peak MR: no to mild/moderate MR (no MR, MR1+ and MR2+) vs moderate/severe MR (MR3+ and MR4+). Results: A good correlation (ρ coefficient= 0.49) was found between the degree of dynamic MR and PASP at peak exercise. Despite similar echocardiographic profile at rest patients with significant peak MR (MR≥3+) had worse exercise performance (lower peak VO2, O2 pulse and workload) and impaired ventilatory efficiency (higher VE/VCO2 slope). Conclusions: In HF patients the severity of exercise-induced MR is associated with the most unfavorable performance and pulmonary hemodynamic response. A combined approach with CPET and echocardiographic assessment can help to early unmask and target functional MR and its related unfavorable phenotypes.


Heart ◽  
2019 ◽  
pp. heartjnl-2018-314173 ◽  
Author(s):  
Khibar Salah ◽  
Susan Stienen ◽  
Yigal M Pinto ◽  
Luc W Eurlings ◽  
Marco Metra ◽  
...  

BackgroundWe assessed the prognostic significance of absolute and percentage change in N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels in patients hospitalised for acute decompensated heart failure with preservedejection fraction (HFpEF) versus heart failure with reduced ejection fraction (HFrEF).MethodsPatients with left ventricular ejection fraction ≥50% were categorised as HFpEF (n=283), while those with <40% as were categorised as HFrEF (n=776). Prognostic values of absolute and percentage change in NT-proBNP levels for 6 months all-cause mortality after discharge were assessed separately in patients with HFpEF and HFrEF by multivariable adjusted Cox regression analysis. Comorbidities were compared between heart failure groups.ResultsDischarge NT-proBNP levels predicted outcome similarly in HFpEF and HFrEF: for any 2.7-factor increase in NT-proBNP levels, the HR for mortality was 2.14 for HFpEF (95% CI 1.48 to 3.09) and 1.96 for HFrEF (95% CI 1.60 to 2.40). Mortality prediction was equally possible for NT-proBNP reduction of ≤30% (HR 4.60, 95% CI 1.47 to 14.40 and HR 3.36, 95% CI 1.93 to 5.85 for HFpEF and HFrEF, respectively) and for >30%–60% (HR 3.28, 95% CI 1.07 to 10.12 and HR 1.79, 95% CI 0.99 to 3.26, respectively), compared with mortality in the reference groups of >60% reductions in NT-proBNP levels. Prognostically relevant comorbidities were more often present in patients with HFpEF than patients with HFrEF in low (≤3000 pg/mL) but not in high (>3000 pg/mL) NT-proBNP discharge categories.ConclusionsOur study highlights—after demonstrating that NT-proBNP levels confer the same relative risk information in HFpEF as in HFrEF—the possibility that comorbidities contribute relatively more to prognosis in patients with HFpEF with lower NT-proBNP levels than in patients with HFrEF.


2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
P E Bartko ◽  
G Heitzinger ◽  
H Arfsten ◽  
N Pavo ◽  
G Spinka ◽  
...  

Abstract Introduction A recently proposed conceptual framework seeks to rearrange the effective regurgitant orifice area (EROA) and regurgitant volume (RegVol) cut-offs according to left ventricular end-diastolic volume (LVEDV) and left ventricular ejection fraction (LVEF) in functional mitral regurgitation introducing “disproportionate FMR” to describe clinically meaningful FMR. The conceptual framework, however, remains hypothetical. Purpose To test the significance of disproportionate FMR. Methods Data of 291 heart failure patients with reduced ejection fraction (HFrEF) under guideline directed therapy were embedded into this conceptual framework (Figure 1A). The black line represents the relationship when the degree of FMR is proportionate to LVEDV with a regurgitant fraction of (RegFrac) of 50%. The dashed lines represent the degree of uncertainty determined by the imprecision inherent to the measurement of RegFrac defined as 2SD for inter- and intraobserver variability by Bland-Altmann analysis (equals ±6.6%). Cox-regression and Kaplan-Meier analysis were applied to assess the association between FMR proportionality and mortality. Results Median age was 68 years (IQR 61–75), 77% were male. Median LVEF was 25% (IQR 18–33) and LVEDV was 214ml (IQR 165–267). Disproportionate FMR was present in 71 patients (24%) (red dots Figure 1A) with a median EROA of 0.26cm2 (IQR 0.18–0.34) and a median RegVol of 42ml (IQR 28–52), proportionate FMR (yellow dots Figure 1 A) in 81 patients (28%) with a median EROA of 0.12cm2 (IQR 0.09–0.17) and a median RegVol of 18ml (IQR 14–27). During 7-years follow-up, 166 patients died. Disproportionate FMR was associated with excess mortality compared to patients with non-severe FMR (HR 1.97, 95% CI 1.04–0.71, P<0.001), whereas proportionate FMR was not associated with increased long-term mortality (HR 1.04, 95% CI −1.53–0.71, P=0.83, Figure 1B). Figure 1. Panel A and B Conclusion Every fifth patient suffers from disproportionate FMR which conveys a two-fold increased risk of mortality. Disproprtionate FMR corresponds to an EROA of roughly 0.3cm2 and a RegVol of 45ml – the unifying intersection between ESC and ACC/AHA guidelines to define severe FMR. The RegFrac provides a measure proportionated to left ventricular size and function supporting its use to define clinically relevant FMR. However, RegFrac is subject to compound error due to imputation of multiple measurements limiting its use as the leading contender for FMR grading. Regardless of the term used to describe clinically significant FMR, the conceptual framework emphasizes the unmet clinical need for recalibrated cut-offs for FMR severity condensed to an algorithm that combines the strengths of several measurements of FMR severity in an integrated manner.


2021 ◽  
Vol 23 (Supplement_G) ◽  
Author(s):  
Leonardo Borsi ◽  
Davide Lazzeroni ◽  
Luca Moderato ◽  
Claudio Stefano Centorbi ◽  
Matteo Bini ◽  
...  

Abstract Aims Arterial hypertension (AHT) represents the leading cause of heart failure (HF). A complex cardiovascular (CV) continuum of events leads to the progression from AHT to left ventricular hypertrophy (LVH), the hallmark of hypertensive heart (HH), towards heart failure with preserved ejection fraction (HFpEF) or reduced ejection fraction (HFrEF). Cardiopulmonary exercise testing (CPET) represents an important tool to evaluate HF patients (both with HFpEF and HFrEF) allowing quantification of functional capacity and mechanisms of dyspnoea as well as providing prognostic markers. To investigate CPET responses in AHT patients at various stages of disease progression from AHT to LVH and HF with preserved and reduced ejection fraction. Methods and results From a CPET registry of 1.397 consecutive subjects, 92 patients were selected (matched according to age, gender, BMI, CV risk factors, beta-blockers) and divided into four groups: 23 AHT patients without LVH, 23 HH patients, 23 HFpEF patients and 23 HFrEF. HFrEF were defined according to LV-EF values while HFpEF were defined according to the presence of NYHA Class ≥2 and HFA-PEFF Score. Mean age was 65 ± 10 years, mean BMI was 28.5 ± 5, male gender was prevalent 83% and 33% had diabetes. Both HFpEF and HFrEF showed lower cardiorespiratory fitness (peak VO2; P &lt; 0.001), cardiovascular efficiency (VO2/Watt slope: P &lt; 0.001), oxygen pulse (VO2/HR: P &lt; 0.001), cardiac output (P &lt; 0.001) and stroke volume (P &lt; 0.001) at peak as well as lower chronotropic response (P &lt; 0.001), ventilatory efficiency (VE/VCO2 slope: P &lt; 0.001), and heart rate recovery (HRR: P = 0.004) compared with both AHT and HH groups. Interestingly, no differences between HFpEF and HFrEF have been found in all CPET data except for chronotropic response (using Tanaka equation), lower in HFpEF (37.5 ± 16.5 vs. 53.5 ± 20.5; P &lt; 0.001) and ventilatory efficiency, lower in HFrEF (VE/VCO2 slope: 32 ± 5 vs. 37 ± 10; P &lt; 0.001). Finally, adding functional capacity (peak VO2) data to ESC Criteria an improvement in HFpEF diagnosis accuracy was found, with 82% sensitivity and 90% specificity (AUC: 859—95% CI: 754–963; P &lt; 0.0001). Conclusions Despite the intrinsic differences in ejection fraction, both HFpEF and HFrEF shares similar cardiopulmonary mechanisms and cardiovascular responses to exercise. CPET may represent a useful tool in order to identify and stratify hypertensive heart patients with HFpEF with high diagnostic accuracy.


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