The application of cardiopulmonary exercise test in heart failure with preserved ejection fraction

Heart failure with preserved ejection fraction (HFpEF) is a prevalent clinical syndrome with a complex diagnosis, associated with various comorbidities and high rates of cardiovascular events. Cardiopulmonary exercise testing (CPET) plays an essential role in understanding the mechanisms of exercise limitation and in complementing the diagnosis of HFpEF, but it presents several gaps to be explored in risk prediction. This article reviews the literature on current pathophysiological, diagnostic, and prognostic aspects of HFpEF. Subsequently, the role of CPET in [...]

Getting old can be tough. Cataracts form, joints deteriorate, arteries stiffen, and bone demineralizes. The heart is certainly not immune to senescence. Diastolic function shows perhaps the greatest deterioration: ventricular compliance decreases, and diastolic relaxation becomes prolonged.[1][1], [

This chapter provides the most relevant knowledge on the role of cardiopulmonary exercise testing (CPET) in heart failure, key methodological aspects are discussed, the importance of careful interpretation of CPET data is highlighted and areas of future work. Cardiovascular disease remains one of the biggest challenges to healthcare professionals in the United Kingdom and worldwide. Common symptoms and physical presentations of heart failure include dyspnoea, fatigue and peripheral and/or pulmonary oedema. A hallmark indicator of heart failure is also a reduced exercise capacity, indicating that heart failure is a disease of reduced oxygen availability/consumption. Valuable clinical information requires sound measurements that are precise and repeatable so that comparisons within one person over time, as well as against clinical criteria, can be made with confidence. Recent data clearly suggest that multiple biological systems are affected in patients with heart failure.

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

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 < 0.001), cardiovascular efficiency (VO2/Watt slope: P < 0.001), oxygen pulse (VO2/HR: P < 0.001), cardiac output (P < 0.001) and stroke volume (P < 0.001) at peak as well as lower chronotropic response (P < 0.001), ventilatory efficiency (VE/VCO2 slope: P < 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 < 0.001) and ventilatory efficiency, lower in HFrEF (VE/VCO2 slope: 32 ± 5 vs. 37 ± 10; P < 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 < 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.

Cardiopulmonary exercise test is a combination of power increasing exercise and computer technology to measure the parameters of ventilation, circulation and gas exchange during body movement by real-time breathing monitoring.It can accurately detect exercise tolerance, cardiac reserve function and severity of disease in patients with cardiovascular and pulmonary diseases.Pulmonary arterial hypertension is caused by pulmonary artery disease, which leads to the increase of pulmonary artery pressure, pulmonary vascular resistance, right cardiac dysfunction, right heart failure, and eventually leads to death.The application of cardiopulmonary exercise test in patients with pulmonary arterial hypertension is summarized as follows. Key words: Cardiopulmonary exercise test; Pulmonary arterial hypertension; Application

Exercise testing in heart failure with preserved ejection fraction: an appraisal through diagnosis, pathophysiology and therapy – A clinical consensus statement of the Heart Failure Association and European Association of Preventive Cardiology of the European Society of Cardiology

The objectives of exercise testing in congestive heart failure (CHF) may be summarized as follows: (a) detect impaired cardiac performance, (b) grade severity of cardiac failure and classify functional capability, and (c) assess effects of interventions. Several different methods are available to make these assessments, and we have to ask ourselves how well exercise testing achieves these objectives. It has to be kept in mind that the power generated by the exercising muscles is dependent on the oxygen delivery to the skeletal muscles. Oxygen uptake is the result of an integrated performance of the lungs, heart, and peripheral circulation. In patients, as well as in normal subjects, oxygen uptake is related to hemodynamic indices such as cardiac output, stroke volume, or exercise duration when a stepwise regulated maximal exercise protocol is used. However, there are major differences in the concept of a true maximum in normal subjects versus heart failure patients. Fit-normal subjects will achieve a real maximal oxygen uptake, whereas patients may stop testing before a maximum is reached because of symptoms such as dyspnea or leg fatigue. Therefore, it is better if the actual oxygen uptake can be measured. "Peak" rather than true maximal oxygen uptake has been suggested for the classification of the severity of heart failure. Peripheral factors modify the cardiac output through such factors as vascular resistance, organ function, and hormonal release. Maximal exercise will stress the cardiovascular system to a point where the weakest chain will impose a limiting effect.(ABSTRACT TRUNCATED AT 250 WORDS)

Heart failure with preserved ejection fraction (HFpEF) is a multifactorial clinical syndrome involving a rather complex pathophysiologic substrate and quite a challenging diagnosis. Exercise intolerance is a major feature of HFpEF, and in many cases, diagnosis is suspected in subjects presenting with exertional dyspnea. Cardiopulmonary exercise testing (CPET) is a noninvasive, dynamic technique that provides an integrative evaluation of cardiovascular, pulmonary, hematopoietic, neuropsychological, and metabolic functions during maximal or submaximal exercise. The assessment is based on the principle that system failure typically occurs when the system is under stress, and thus, CPET is currently considered to be the gold standard for identifying exercise intolerance, allowing the differential diagnosis of underlying causes. CPET is used in observational studies and clinical trials in HFpEF; however, in most cases, only a few from a wide variety of CPET parameters are examined, while the technique is largely underused in everyday cardiology practice. This article discusses the basic principles and methodology of CPET and studies that utilized CPET in patients with HFpEF, in an effort to increase awareness of CPET capabilities among practicing cardiologists.

Purpose of ReviewCardiac amyloidosis (CA) constitutes an important etiology of heart failure with preserved ejection fraction (HFpEF) or heart failure with mildly reduced ejection fraction (HFmrEF). Since patients with CA show early exhaustion, we aimed to investigate whether non-exertional variables of cardiopulmonary exercise testing (CPET) provide additional information in comparison to traditional peak oxygen consumption (VO2peak).Recent FindingsWe retrospectively investigated CPET variables of patients with HFpEF and HFmrEF with (n = 21) and without (n = 21, HF) CA at comparable age and ejection fraction. Exertional and non-exertional CPET variables as well as laboratory and echocardiographic markers were analyzed. The primary outcome was the difference in CPET variables between groups. The secondary outcome was rehospitalization in patients with CA during a follow-up of 24 months. Correlations between CPET, NTproBNP, and echocardiographic variables were calculated to detect patterns of discrimination between the groups. HF patients with CA were inferior to controls in most exertional and non-exertional CPET variables. Patients with CA were hospitalized more often (p = 0.002), and rehospitalization was associated with VE/VCO2 (p = 0.019), peak oxygen pulse (p = 0.042), the oxygen equivalent at the first ventilatory threshold (p = 0.003), circulatory (p = 0.024), and ventilatory power (p < .001), but not VO2peak (p = 0.127). Higher performance was correlated with lower E/e’ and NTproBNP as well as higher resting heart rate and stroke volume in CA.SummaryPatients with CA displayed worse non-exertional CPET performance compared to non-CA HF patients, which was associated with rehospitalization. Differences between correlations of resting echocardiography and CPET variables between groups emphasize different properties of exercise physiology despite comparable ejection fraction.

Hemodynamic Correlates and Diagnostic Role of Cardiopulmonary Exercise Testing in Heart Failure With Preserved Ejection Fraction

Introduction: Muscular microcirculatory dynamic changes during muscle strength effort remain to be studied in different heart failure (HF) phenotypes and severities. This study compare the muscular microcirculatory responses during strength exercise testing in HF with preserved ejection fraction (HFpEF) with reduced ejection fraction (HFrEF) and disease severities. Hypothesis: HFpEF patients display worse microvascular function during strength exercise testing, particularly in those with more severe disease (according to Weber classification). Methods: Seventeen HF patients (HFpEF, n=10, HFrEF n=7, mean age 57±6 years) underwent muscular microcirculatory dynamics assessment by near-infrared spectroscopy (tissue saturation index, TSI, %; oxyhemoglobin, O 2 Hb, μM and deoxyhemoglobin concentration, HHb, μM) during concentric isokinetic strength exercise testing (20 repetitions at an angular velocity of 180°/s) and subsequent recovery. Patients were analyzed according to their phenotype and disease severity (Weber A+B and Weber C). Results: From HFpEF, Weber Class C patients presented a poor capability to achieve higher oxygen extraction during exercise than Class A and B. Among those with Weber C, while HFrEF patients presented lower oxyhemoglobin (O 2 Hb, μM) (-18.9±11.8 vs.-8.9±5.6, p=0.029) during exercise, HFpEF had lower O 2 Hb during the recovery period (-3.0±3.4 vs. 5.9±2.8, p=0.007). Figure 1 illustrates muscular oxygenation dynamics in heart failure phenotypes and severities. No differences for TSI and HHb, neither on O 2 Hb in between phenotypes on Weber A+B severity. Conclusions: Preliminary findings regarding muscular microcirculatory oxygen reduction during isokinetic muscle strength testing are present in HFpEF patients more severely impaired (Weber C), which helps explain exercise intolerance in Heart Failure, reinforcing a worst circulatory periphery environment in such phenotype.

BackgroundThis study aimed to compare the independent and incremental prognostic value of peak oxygen consumption (VO2) and minute ventilation/carbon dioxide production (VE/VCO2) in heart failure (HF) with preserved (HFpEF), midrange (HFmEF), and reduced (HFrEF) ejection fraction (LVEF).Methods and ResultsIn 195 HFpEF (LVEF ≥50%), 144 HFmEF (LVEF 40–49%), and 630 HFrEF (LVEF <40%) patients, we assessed the association of cardiopulmonary exercise testing variables with the composite outcome of death, left ventricular assist device implantation, or heart transplantation (256 events; median follow‐up of 4.2 years), and 2‐year incident HF hospitalization (244 events). In multivariable Cox regression analysis, greater association with outcomes in HFpEF than HFrEF were noted with peak VO2 (HR [95% confidence interval]: 0.76 [0.67–0.87] versus 0.87 [0.83–0.90] for the composite outcome, Pinteraction=0.052; 0.77 [0.69–0.86] versus 0.92 [0.88–0.95], respectively for HF hospitalization, Pinteraction=0.003) and VE/VCO2 slope (1.11 [1.06–1.17] versus 1.04 [1.03–1.06], respectively for the composite outcome, Pinteraction=0.012; 1.10 [1.05–1.15] versus 1.04 [1.03–1.06], respectively for HF hospitalization, Pinteraction=0.019). In HFmEF, peak VO2 and VE/VCO2 slope were associated with the composite outcome (0.79 [0.70–0.90] and 1.12 [1.05–1.19], respectively), while only peak VO2 was related to HF hospitalization (0.81 [0.72–0.92]). In HFpEF and HFrEF, peak VO2 and VE/VCO2 slope provided incremental prognostic value beyond clinical variables based on the C‐statistic, net reclassification improvement, and integrated diagnostic improvement, with models containing both measures demonstrating the greatest incremental value.ConclusionsBoth peak VO2 and VE/VCO2 slope provided incremental value beyond clinical characteristics and LVEF for predicting outcomes in HFpEF. Cardiopulmonary exercise testing variables provided greater risk discrimination in HFpEF than HFrEF.

Although right-sided filling pressures often mirror left-sided filling pressures in systolic heart failure, it is not known whether a similar relationship exists in heart failure with preserved ejection fraction. Eleven subjects with heart failure with preserved ejection fraction underwent right heart catheterization at rest and under loading conditions manipulated by lower body negative pressure and saline infusion. Right atrial pressure (RAP) was classified as elevated when >or=10 mm Hg and pulmonary capillary wedge pressure (PCWP) when >or=22 mm Hg. If both the RAP and the PCWP were elevated or both not elevated, they were classified as concordant; otherwise, they were classified as discordant. Correlation of RAP and PCWP was determined by a repeated measures model. Among 66 paired measurements of RAP and PCWP, 44 (67%) had a low RAP and PCWP and 8 (12%) a high RAP and PCWP, yielding a concordance rate of 79%. In a sensitivity analysis performed by varying the definition of elevated RAP (from 8 to 12 mm Hg) and PCWP (from 15 to 25 mm Hg), the mean+/-SD concordance of RAP and PCWP was 76+/-10%. The correlation coefficient of RAP and PCWP for the overall cohort was r=0.86 (P<0.0001). Right-sided filling pressures often reflect left-sided filling pressures in heart failure with preserved ejection fraction, supporting the role of estimation of jugular venous pressure to assess volume status in this condition.

Clinical application and research progress of cardiopulmonary exercise testing in heart failure with preserved ejection fraction