Risk stratification in hf with mid-range LVEF: the role of cardiopulmonary exercise testing

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) <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 <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<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<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 <12 mL/kg/min, VE/VCO2 >35 and EOV identified patients at higher risk for events (all p<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<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<0.001; and HR per unit: 0.99; CI: 0.95–1.03; p=0.512, respectively). ROC curve analysis demonstrated that a pVO2 >16.7 and >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<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

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The role of cardiopulmonary exercise testing in a contemporary heart failure population

European Journal of Preventive Cardiology ◽

10.1093/eurjpc/zwab061.015 ◽

2021 ◽

Vol 28 (Supplement_1) ◽

Author(s):

P Garcia Bras ◽

A Valentim Goncalves ◽

J Reis ◽

T Pereira Da Silva ◽

R Ilhao Moreira ◽

...

Keyword(s):

Heart Failure ◽

Risk Stratification ◽

Exercise Testing ◽

Predictive Power ◽

Cardiopulmonary Exercise Testing ◽

Composite Endpoint ◽

Left Ventricular ◽

Left Ventricular Ejection ◽

Discriminative Power ◽

Cardiopulmonary Exercise

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

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Additive prognostic value of cardiopulmonary exercise testing in elderly patients with heart failure

Clinical Science ◽

10.1042/cs20080111 ◽

2009 ◽

Vol 116 (5) ◽

pp. 415-422 ◽

Cited By ~ 7

Author(s):

Angela B. Scardovi ◽

Renata De Maria ◽

Andrea Celestini ◽

Silvia Perna ◽

Claudio Coletta ◽

...

Keyword(s):

Heart Failure ◽

Risk Stratification ◽

Elderly Patients ◽

Ventricular Function ◽

Exercise Testing ◽

Cardiopulmonary Exercise Testing ◽

Left Ventricular ◽

Left Ventricular Ejection ◽

Cardiopulmonary Exercise ◽

Production Ratio

To date, the role of CPET (cardiopulmonary exercise testing) for risk stratification in elderly patients with HF (heart failure) with depressed or preserved ventricular function has not been evaluated. In the present study, we analysed whether CPET is useful in predicting outcome in this population. A total of 220 NYHA (New York Heart Association) class I–III patients with HF ≥70 years of age [median age, 75 years; 23% had NYHA class III; and 59% had preserved ventricular systolic function (left ventricular ejection fraction ≥40%)] performed maximal CPET (peak expiratory exchange ratio >1.00). Median peak oxygen uptake was 11.9 ml·kg−1 of body weight·min−1, median V̇E/V̇CO2 slope (slope of the minute ventilation/carbon dioxide production ratio) was 33.2 and 45% had an EVR (enhanced ventilatory response) to exercise (V̇E/V̇CO2 slope ≥34). During 19 months of follow-up, 94 patients (43%) met the combined end point of death and hospital admission for worsening HF, arrhythmias or acute coronary syndromes. By Cox multivariable analysis, a creatinine clearance of <50 ml/min {HR (hazard ratio), 1.657 [95% CI (confidence interval), 1.055–2.602]} and EVR [HR, 1.965 (95% CI, 1.195–3.231)] were the best predictors of outcome, while ventricular function had no influence on prognosis. In conclusion, in elderly patients with HF, a steeper V̇E/V̇CO2 slope provides additional information for risk stratification across the spectrum of ventricular function and identifies a high-risk population, commonly not considered in exercise testing guidelines.

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Risk stratification and survival in patients with HFmrEF: the role of cardiopulmonary exercise testing

European Heart Journal ◽

10.1093/eurheartj/ehab724.0848 ◽

2021 ◽

Vol 42 (Supplement_1) ◽

Author(s):

J.G Westphal ◽

P.C Schulze

Keyword(s):

Heart Failure ◽

Ejection Fraction ◽

Risk Stratification ◽

Exercise Testing ◽

Primary Endpoint ◽

Cardiopulmonary Exercise Testing ◽

Cardiopulmonary Exercise ◽

All Cause Mortality

Abstract Background The prognostic value of cardiopulmonary exercise testing (CPET) is established for risk stratification in patients with heart failure (HF) and reduced ejection fraction (HFrEF). Since the introduction of HF with mid-range ejection fraction (HFmrEF) as an additional category in 2016, optimal management strategy and risk stratification for these patients is a field of ongoing research. Purpose Left ventricular ejection fraction (LVEF) is only one part of the picture when planning treatment and estimating long time risk for patients with HF. We planned to investigate the predictive long-term value of exercise intolerance as measured by CPET in patients with HFmrEF in comparison to HFrEF. Methods We performed a single-center retrospective cohort study of ambulatory consecutive patients that showed signs of heart failure (NYHA functional class II or III) and had a LVEF of 49% or below as measured by echocardiography at the time of CPET. All patients underwent CPET evaluation with an upright bicycle between 2015–2017. The primary endpoint of all-cause mortality as well as the secondary composite endpoint of all-cause mortality or heart transplant/ventricular assist device implantation (transplant/VAD free survival) were assessed. Results For the primary analysis, 253 patients (mean age 61.2±13.0 years, 82.6% male) were included. 68 patients showed an LVEF between 40 and 49% (HFmrEF) whereas 185 patients had an LVEF of below 40% (HFrEF). HF etiology was in 31.3% ischemic. Mean BNP values were 788±1061 pg/ml while HFmrEF patients had on average lower values than HFrEF (322±676 vs. 945±1121, p<0.001). Patients were followed up for a median of 4.2 years (IQR: 3.5–5.0 years). Over this period, the primary and secondary end-point occurred in 22.5%/30.8% of patients. Patients in the HFmrEF group showed a higher mean peak oxygen uptake compared to HFrEF (pVO2; 17.3±4.6 vs 14.2±3.7 ml/min/kg, p<0.001), peak exercise power (Pmax; 111±49 vs 91±38 Watt, p=0.02) and peak oxygen pulse (pO2/HR; 12.6±4.2 vs 10.4±4.1 ml/min/kg, p<0.001). The Kaplan-Meier-Estimate showed a significant difference in survival for both HFmrEF and HFrEF who had pVO2 below 14 ml/min/kg (Log Rank: Chi2: 4.45, p=0.035 and Chi2: 10.05, p=0.02). In univariate Cox regression, pVO2 was predictive of the primary endpoint (HR per +1 mL/kg/min: 0.81; CI: 0.71–0.93; p=0.002 and HR per +1 mL/kg/min: 0.84; CI: 0.77–0.92; p<0.001) in both groups as was Pmax and pO2/HR (p<0.05 for both variables in both groups). Conclusion As in HFrEF, CPET is a useful tool to stratify risk in HFmrEF as well. Our findings support the prognostic role of pVO2 as well as pO2/HR and Pmax in HF with mid-range LVEF. Using a cut off of pVO2 14 ml/min/kg selected patients at risk with similar long-term prognosis as in the HFrEF cohort. Further research to identify subgroups at risk within the heterogeneous group of HFmrEF is warranted for optimal risk stratification. FUNDunding Acknowledgement Type of funding sources: None.

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Role of confirmed and potential predictors of an unfavorable outcome in heart failure in everyday clinical practice

Irish Journal of Medical Science (1971 -) ◽

10.1007/s11845-020-02477-z ◽

2021 ◽

Author(s):

Anna Chuda ◽

Maciej Banach ◽

Marek Maciejewski ◽

Agata Bielecka-Dabrowa

Keyword(s):

Heart Failure ◽

Exercise Testing ◽

Clinical Decision Making ◽

Cardiopulmonary Exercise Testing ◽

High Sensitivity ◽

Left Ventricular ◽

Unfavorable Outcome ◽

Left Ventricular Ejection ◽

Monitoring Method ◽

Ventricular Ejection Fraction

AbstractHeart failure (HF) is the only cardiovascular disease with an ever increasing incidence. HF, through reduced functional capacity, frequent exacerbations of disease, and repeated hospitalizations, results in poorer quality of life, decreased work productivity, and significantly increased costs of the public health system. The main challenge in the treatment of HF is the availability of reliable prognostic models that would allow patients and doctors to develop realistic expectations about the prognosis and to choose the appropriate therapy and monitoring method. At this moment, there is a lack of universal parameters or scales on the basis of which we could easily capture the moment of deterioration of HF patients’ condition. Hence, it is crucial to identify such factors which at the same time will be widely available, cheap, and easy to use. We can find many studies showing different predictors of unfavorable outcome in HF patients: thorough assessment with echocardiography imaging, exercise testing (e.g., 6-min walk test, cardiopulmonary exercise testing), and biomarkers (e.g., N-terminal pro-brain type natriuretic peptide, high-sensitivity troponin T, galectin-3, high-sensitivity C-reactive protein). Some of them are very promising, but more research is needed to create a specific panel on the basis of which we will be able to assess HF patients. At this moment despite identification of many markers of adverse outcomes, clinical decision-making in HF is still predominantly based on a few basic parameters, such as the presence of HF symptoms (NYHA class), left ventricular ejection fraction, and QRS complex duration and morphology.

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Abstract 17232: Cardiopulmonary Exercise Testing in Diabetic Chronic Heart Failure Patients With Microalbuminuria

Circulation ◽

10.1161/circ.142.suppl_3.17232 ◽

2020 ◽

Vol 142 (Suppl_3) ◽

Author(s):

Thida tabucanon ◽

Timothy Engelman ◽

Sanjeeb S Bhattacharya ◽

J Emanuel Finet ◽

Wai Hong W Tang

Keyword(s):

Oxygen Consumption ◽

Exercise Testing ◽

Beta Blocker ◽

Multivariable Analysis ◽

Cardiopulmonary Exercise Testing ◽

Left Ventricular ◽

Peak Oxygen Consumption ◽

Left Ventricular Ejection ◽

Cardiopulmonary Exercise ◽

History Of

Introduction: Microalbuminuria can be a presentation of microvascular complication in diabetes mellitus (DM). Hypothesis: Microalbuminuria is associated with impaired exercise performance in chronic HF with DM patients. Methods: We retrospectively analyzed a cardiopulmonary exercise testing (CPET) database in 255 chronic HF patients with DM that had urine microalbumin test between December 2012 and September 2019. Demographic data and CPET parameters were compared between the patients who had and had not microalbuminuria which was defined by microalbumin/creatinine ratio ≥ 30 mg/g. Peak oxygen consumption (peak VO 2 ) ≤ 14 ml/kg/min and ≤ 12 ml/kg/min if had history of beta-blocker uses were classified as low peak VO 2 and used in multivariable analysis. Results: There were a total 92 patients (36.1%) that had microalbuminuria. Mean age was not significant different between the patients with and without microalbuminuria (57.7 vs 59.4 years, p = 0.26). The patients with microalbuminuria had lower body mass index (BMI; 30.8 vs. 32.7 kg/m 2 , p = 0.014) and had more history of beta-blocker (BB) uses (81.5% vs. 69.3%, p = 0.038), no significant different in other medication uses. Left ventricular ejection fraction (LVEF) was significant lower in patients with microalbuminuria (35.8% vs. 41.5%, p = 0.028). The patients with microalbuminuria had significant higher prevalence of low peak VO 2 (45.7% vs. 30.1%, p = 0.015) and lower peak stroke work (VO 2 /HR; 11.5 vs. 12.8 ml/ beat, p = 0.008). No significant different in ventricular efficiency slope (VE/VCO 2 ; 37.1 vs. 35.4, p = 0.094), Multivariable analysis showed that proteinuria was independently associated with low peak VO 2 after adjusted for age, sex, BMI LVEF, history of BB uses, VE/VCO 2 and HR at peak VO 2 , (odds ratio = 3.83, p < 0.001). Conclusions: Microalbuminuria was independently associated with low peak oxygen consumption in chronic HF with DM patients.

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Cardiopulmonary exercise testing in patients undergoing radical cystectomy (open, laparoscopic and robotic)

Journal of Clinical Urology ◽

10.1177/2051415814537823 ◽

2014 ◽

Vol 7 (6) ◽

pp. 374-379 ◽

Cited By ~ 2

Author(s):

Kimberley Hoyland ◽

Nikhil Vasdev ◽

James M Adshead ◽

Andrew Thorpe

Keyword(s):

Risk Stratification ◽

Radical Cystectomy ◽

Exercise Testing ◽

Functional Assessment ◽

Postoperative Care ◽

Assessment Tool ◽

Cardiopulmonary Exercise Testing ◽

Cardiopulmonary Exercise

The use of cardiopulmonary exercise testing (CPET) is gaining popularity as a preoperative functional assessment tool and is a useful adjunct to risk stratification before radical cystectomy. It is important for urologists to understand the indications, contraindications, methodology and different parameters evaluated during CPET assessment and use this information acquired to tailor pre-, intra- and postoperative care in patients undergoing a radical cystectomy. We present a review on the increasing role of CPET in patients undergoing a radical cystectomy.

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ASSET: Alternative schedule sunitinib in metastatic renal cell carcinoma (RCC)—Cardiopulmonary exercise testing (CPET).

Journal of Clinical Oncology ◽

10.1200/jco.2021.39.6_suppl.300 ◽

2021 ◽

Vol 39 (6_suppl) ◽

pp. 300-300

Author(s):

Michael Roger Harrison ◽

David Bartlett ◽

Tian Zhang ◽

Andrew J. Armstrong ◽

Aubrie Coburn ◽

...

Keyword(s):

Physical Fitness ◽

Primary Endpoint ◽

Cardiopulmonary Exercise Testing ◽

Left Ventricular ◽

Left Ventricular Ejection ◽

Anxiety And Depression ◽

Ventricular Ejection Fraction ◽

Change Scores ◽

Secondary Endpoints ◽

And Function

300 Background: Sunitinib (SUN) is a vascular endothelial growth factor (VEGF) tyrosine kinase inhibitor (TKI) approved for treatment of advanced RCC and high risk RCC after nephrectomy. Evidence suggests that a 2 week (wk) on, 1 wk off schedule (2/1) of SUN administration may be more tolerable than the standard 4 wk on, 2 wk off schedule (4/2). We investigated changes in cardiopulmonary function and related parameters over time in RCC patients treated with both schedules of SUN. Methods: Patients starting SUN for RCC, with KPS ≥80 and normal organ and marrow function, were enrolled and randomized 1:1 to schedule 4/2 or 2/1. Subjects were required to be able to walk and jog on a treadmill and to complete an acceptable CPET at baseline (BL). Primary endpoint was change in peak oxygen uptake (VO2peak) on both schedules at 12 wk from BL. Key secondary endpoints were change from BL to 12 wk in: left ventricular ejection fraction (LVEF), upper and lower body strength (1-RM), functional measures (chair stand, timed up-and-go [TUG], 6-minute walk test [6MWT], quality of life (QOL; FACT-Fatigue, FKSI-19), anxiety and depression (HADS) and exercise behavior (Godin Leisure Score). ANCOVA models controlling for baseline values were used to analyze the primary and secondary endpoints. Results: Between 11/20/2017 and 6/24/2019, 9 out of a planned 30 patients consented to participate at Duke. Two patients declined to participate and 7 patients were enrolled on study: 4 on Arm A and 3 on Arm B. All 7 patients completed the 12 wk study. Median age, BMI, and VO2peak were 65 yrs, 30.5 kg/m2, and 19.2 ml kg−1 min−1. We observed no difference in the primary endpoint of VO2peak between arms (p=0.84). We report BL to 12 wk change scores for all patients starting SUN (Table). In addition, mean change scores (SE) for QOL by FACIT-Fatigue and FKSI-19 were -2.88 (1.5) and 1.2 [9.8]; anxiety and depression by HADS 1.14 (1.3); and physical activity 1.14 (1.7). Conclusions: We observed non-significant declines in most measures of physical fitness and function during the first 12 wk of treatment with SUN. To our knowledge, this is the first reported study of these parameters in patients with RCC. Given that a VEGF TKI, alone and with an immune checkpoint inhibitor, remains a standard of care for metastatic ccRCC, studies should be undertaken to examine whether exercise training can prevent declines in physical fitness and function. Clinical trial information: NCT03109015 . [Table: see text]

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