Invasive Cardiopulmonary Exercise Testing Research Articles

Abstract 14283: Coronary Microvascular Function is Correlated With Peak Exercise Capacity in Patients With Unexplained Cardiac Exertion Symptoms and Non-obstructive Coronary Artery Disease

Introduction: Coronary microvascular dysfunction (CMD) is prevalent in symptomatic patients with no obstructive coronary artery disease. We postulated that exercise capacity and cardiac output augmentation in response to exercise are linked to coronary microvascular function in this patient population. Methods: Fifty-one consecutive patients with unexplained cardiac exertion symptoms, non-obstructive coronary artery disease on angiography (<50% stenosis), and normal left ventricular ejection fraction (>50%) who underwent concurrent clinically indicated coronary reactivity testing and invasive cardiopulmonary exercise testing (CPEX) were included. Microvascular function was assessed by coronary flow reserve (CFR; hyperemic/resting flow) in response to intracoronary adenosine injection. Cardiac output (CO) was calculated at rest and peak exercise using Fick’s formula. CO limitation was defined as a measured (peak CO - resting CO) <80% than the expected [6*absolute ΔVO 2 (Peak VO 2 -Rest VO 2 ) increase in CO in L/min]. The relationship between CFR, maximal exercise capacity, and CO augmentation at peak exercise was explored. Results: Patients were 56.6±10.5 years old and 73% were females. CFR had a modest positive correlation with measured increase in CO (r=0.42; P=0.003) ( Fig 1A ), and with maximal ergometric exercise capacity [in Watts/Kg] (Pearson’s r=0.33, P=0.02) ( Fig 1B ). Patients with, vs. without impaired cardiac limitations during exercise, had significantly lower CFR levels (2.6±0.5 vs 3.1±0.7; P=0.01) ( Fig 2 ). Conclusion: Impaired coronary microvascular function is associated with lower peak exercise capacity and reduced cardiac output augmentation in response to exercise, underscoring the functional ramification of CMD in symptomatic patients.

Abstract 14369: Assessment of Hemodynamic Response to Exercise in Patients With Advanced Heart Failure

Introduction: Among patients suffering from HFrEF, outcomes are closely associated with quality-of-life and functional capacity. Data are limited regarding exertional cardiopulmonary performance measures in these patients. The objective of this study was to complete a comprehensive analysis of cardiac function among patients with advanced HFrEF during submaximal and peak exercise through an invasive cardiopulmonary exercise test (CPET) on an upright cycle ergometer. Methods: Thirty-five participants with advanced HFrEF (age 59 ± 12) underwent invasive hemodynamic assessment with Swan-Ganz catheter during CPET. Group 1 comprised individuals not on inotropes (N=23, 66%); group 2 was comprised of individuals on inotropes (N=12, 34%). Data were obtained at supine and upright rest, two submaximal levels (steady-states 1-2) of exertion below the ventilatory threshold (VT), and peak exercise. Results: Cohort characteristics are displayed in table 1 . VO 2 max for the overall cohort was severely reduced (11.8 ± 3.3), and was similar between group 1 and 2 (12.1 ± 3.2 v. 10.1 ± 3.5 ml/kg/min, P= 0.71). As displayed in figure 1 , pulmonary arterial and left-sided filling pressures increased dramatically even during submaximal exercise. Cardiac output increased minimally, with only an ~2-fold change from rest to peak exercise for both groups. Conclusions: Among patients with advanced HFrEF, exercise is limited by severe increases in cardiac and pulmonary filling pressures, even during submaximal levels of exercise that mimic real-world activities of daily living, as well as severely impaired inotropic reserve. Inotropes do not appear to improve exertional hemodynamics.

Systemic vascular distensibility relates to exercise capacity in connective tissue disease.

Exercise intolerance is a common clinical manifestation of CTD. Frequently, CTD patients have associated cardio-pulmonary disease, including pulmonary hypertension or heart failure that impairs aerobic exercise capacity (pVO2). The contribution of the systemic micro-vasculature to reduced exercise capacity in CTD patients without cardiopulmonary disease has not been fully described. In this study, we sought to examine the role of systemic vascular distensibility, α in reducing exercise capacity (i.e. pVO2) in CTD patients. Systemic and pulmonary vascular distensibility, α (%/mmHg) was determined from multipoint systemic pressure-flow plots during invasive cardiopulmonary exercise testing with pulmonary and radial arterial catheters in place in 42 CTD patients without cardiopulmonary disease and compared with 24 age and gender matched normal controls. During exercise, systemic vascular distensibility, α was reduced in CTD patients compared with controls (0.20 ± 0.12%/mmHg vs 0.30 ± 0.13%/mmHg, P=0.01). The reduced systemic vascular distensibility α, was associated with impaired stroke volume augmentation. On multivariate analysis, systemic vascular distensibility, α was associated with a decreased exercise capacity (pVO2) and decreased systemic oxygen extraction. Systemic vascular distensibility, α is associated with impaired systemic oxygen extraction and decreased aerobic capacity in patients with CTD without cardiopulmonary disease.

Gas Exchange Score with VE/VCO2 and ETCO2 Reliably Predicts Pulmonary Vascular Disease in Suspected Pulmonary Hypertension

Introduction Non-invasive methods to identify phenotype of pulmonary hypertension (PH) remains a topic of interest. Cardiopulmonary exercise test (CPET) provides gas exchange (GX) parameters including end-tidal carbon dioxide (ETCO2) and ventilation of minute ventilation to carbon dioxide ventilation ratio (VE/VCO2). A direct correlation of these GX parameters with invasive hemodynamics can provide further insight into the ability of GX parameters to predict PH phenotype. Hypothesis Using a direct correlation of gas exchange parameters with invasive hemodynamics, we propose that in subjects with suspected PH, rest gas exchange parameters can reliably predict pulmonary vascular disease. Methods We reviewed clinical, echocardiographic and invasive CPET (iCPET) data for 41 patients. We then analyzed the data with receiver operator curve (ROC) to help estimate the area under the curve (AUC) of different gas exchange parameters to help define the hemodynamics of different PH groups and derive the most appropriate parameters to define PH. *p Results Among the overall cohort, mean age (± SD) was 63.9±11.35 years, and 20 subjects were female (49 %). The distribution of WHO groups of PH based on the final diagnosis among the overall cohort was: 8 patients WHO group I (19.5%), 21 patients WHO group II (51.2%), 3 patients WHO group III (7.3%), 1 patient WHO group IV (2.4%), and 8 patients had no evidence of rest or exercise PH (19.5%). For the purpose of analysis, we created three groups: 1) pulmonary vascular disease (PVD): combination of WHO group I, III and IV, 2) pulmonary venous hypertension (PVH): WHO group II, 3) Control: no PH group. On ROC analysis, rest and exercise ETCO2 and VE/VCO2 had equally high predictive ability to predict exercise PVR > 3 WU (rest ETCO2=0.806, exercise ETCO2=0.880, rest VE/VCO2=0.794, exercise VE/VCO2=0.820). Similar pattern of ETCO2 and VE/VCO2 was identified with prediction of rest PVR >3WU and WHO group I PAH. Based on the ROC analysis, we found that the ideal cutoffs (to predict rest PVR>3WU or exercise PVR>3WU or PVD group) were ≤30 mmHg for ETCO2 and ≥42 for VE/VECO2.Using these cutoffs, we created a scoring system of “rest-only” GX parameters (+1 for ETCO2 ≤30 and VE/VCO2 ≥42; and -1 for vice versa). Each patient would have a total score of -2, 0 or +2. The AUC for this rest-only scoring system to predict exercise PVR >3WU was 0.841. When applied to the whole cohort, score of -2 (n=14) included: 8 PVH and 5 with no PH, score of +2 (n=11) included 6 PVD (percentages shown in figure). Conclusions Among individuals with suspected PH, a composite gas exchange score with VE/VCO2 (≥42) and ETCO2 (≤30 mmHg) reliably predicts PVD.

Dynamic right ventricular function response to incremental exercise in pulmonary hypertension.

Pulmonary hypertension is a progressive disease whose survival is linked to adequate right ventricle adaptation to its afterload. In the current study, we performed an in-depth characterization of right ventricle function during maximum incremental exercise in patients with pulmonary hypertension and how it relates to exercise capacity. A total of 377 pulmonary hypertension patients who completed a maximum symptom-limited invasive cardiopulmonary exercise testing were evaluated to identify 45 patients with heart failure with preserved ejection fraction, 48 with exercise pulmonary hypertension, and 47 with established pulmonary arterial hypertension. These patients were compared to 17 age- and gender-matched normal controls. Load-adjusted right ventricle function was quantified as the ratio of right ventricle stroke work index to pulmonary arterial elastance. All patients with pulmonary hypertension had reduced peak VO2 %predicted compared to controls. Right ventricle function deteriorated for all pulmonary hypertension groups by 50% of peak VO2. Worsening of right ventricle function during freewheeling exercise was associated with greater reduction in peak VO2 compared to those whose right ventricle function deteriorated at later exercise stages (i.e. min 1, 2, and 3). On multivariate analysis, reduced ratio of right ventricle stroke work index to arterial elastance was an independent predictor of peak VO2 %predicted (β-Coefficient –5.46, 95% CI: –9.47 to –1.47, p = 0.01). Right ventricle function deteriorates early during incremental exercise in pulmonary hypertension, occurring by 50% of peak oxygen uptake. The current study demonstrates that right ventricle dysfunction is an early phenomenon during incremental exercise in pulmonary hypertension, occurring by 50% of peak oxygen uptake. The threshold at which right ventricle function is compromised during incremental exercise in pulmonary hypertension influences aerobic capacity and may help guide exercise strategies to mitigate dynamic worsening of right ventricle function during exercise training.

New insights into resting and exertional right ventricular performance in the healthy heart through real-time pressure-volume analysis.

Despite growing interest in right ventricular form and function in diseased states, there is a paucity of data regarding characteristics of right ventricular function - namely contractile and lusitropic reserve, as well as ventricular-arterial coupling, in the healthy heart during rest, as well as submaximal and peak exercise. Pressure-volume analysis of the right ventricle, during invasive cardiopulmonary exercise testing, demonstrates that that the right heart has enormous contractile reserve, with a three- or fourfold increase in all metrics of contractility, as well as myocardial energy production and utilization. The healthy right ventricle also demonstrates marked augmentation in lusitropy, indicating that diastolic filling of the right heart is not passive. Rather, the right ventricle actively contributes to venous return during exercise, along with the muscle pump. Ventricular-arterial coupling is preserved during submaximal and peak exercise in the healthy heart. Knowledge of right ventricular (RV) function has lagged behind that of the left ventricle and historically, the RV has even been referred to as a 'passive conduit' of lesser importance than its left-sided counterpart. Pressure-volume (PV) analysis is the gold standard metric of assessing ventricular performance. We recruited nine healthy sedentary individuals free of any cardiopulmonary disease (42±12years, 78±11kg), who completed invasive cardiopulmonary exercise testing during upright ergometry, while using conductance catheters inserted into the RV to generate real-time PV loops. Data were obtained at rest, two submaximal levels of exercise below ventilatory threshold, to simulate real-world scenarios/activities of daily living, and maximal effort. Breath-by-breath oxygen uptake was determined by indirect calorimetry. During submaximal and peak exercise, there were significant increases in all metrics of systolic function by three- to fourfold, including cardiac output, preload recruitable stroke work, and maximum rate of pressure change in the ventricle (dP/dtmax ), as well as energy utilization as determined by stroke work and pressure-volume area. Similarly, the RV demonstrated a significant, threefold increase in lusitropic reserve throughout exercise. Ventricular-arterial coupling, defined by the quotient of end-systolic elastance and effective arterial elastance, was preserved throughout all stages of exercise. Maximal pressures increased significantly during exercise, while end-diastolic volumes were essentially unchanged. Overall, these findings demonstrate that the healthy RV is not merely a passive conduit, but actively participates in cardiopulmonary performance during exercise by accessing an enormous amount of contractile and lusitropic reserve, ensuring that VA coupling is preserved throughout all stages of exercise.

Determinants of Oxygen Uptake (VO2) among Patients with CF-LVADs

Characterize individual components of VO2 (cardiac output [Qc] and (A-V)O2 difference) at rest and during submaximal and peak exercise among CF-LVAD patients. Thirteen CF-LVAD participants (56±12 yrs, 12 male) and 9 healthy controls 42±12 yrs, 7 male) completed invasive cardiopulmonary exercise testing on a stationary upright cycle ergometer. Hemodynamic data and gas-exchange parameters were collected at rest, two submaximal levels of exercise below the ventilatory threshold, and peak workload. Swan-Ganz catheterization was performed to determine baseline hemodynamics. A conductance catheter was then used to calculate Qc at each stage of exercise. VO2was recorded on a breath-by-breath basis by indirect calorimetry. Blood pressure was continuously monitored by arterial line. Musculoskeletal performance was assessed by calculating the (A-V)O2 difference at each stage of exercise. Cohort characteristics and baseline demographics are demonstrated in table 1. Peak VO2 among CF-LVAD participants was severely reduced compared to healthy controls. When CF-LVAD participants were matched to healthy controls by workload according to VO2 quartiles, the CF-LVAD participants had a hypotensive response to exercise, as well as a blunted rise in Qc, with modest increases only from rest to submaximal exercise (figure 1). As a result, (A-V)O2 difference was higher for CF-LVAD participants than healthy controls at each VO2 quartile. Due to impairments in contractile reserve, CF-LVAD participants exhibit a greater (A-V)O2 difference than healthy individuals when exercising at similar workloads.

Comprehensive Diagnostic Evaluation of Cardiovascular Physiology in Patients With Pulmonary Vascular Disease: Insights From the PVDOMICS Program.

Invasive hemodynamic evaluation through right heart catheterization plays an essential role in the diagnosis, categorization, and risk stratification of patients with pulmonary hypertension. Subjects enrolled in the PVDOMICS (Redefining Pulmonary Hypertension through Pulmonary Vascular Disease Phenomics) program undergo an extensive invasive hemodynamic evaluation that includes repeated measurements at rest and during several provocative physiological challenges. It is a National Institutes of Health/National Heart, Lung, and Blood Institute initiative to reclassify pulmonary hypertension groups based on clustered phenotypic and phenomic characteristics. At a subset of centers, participants also undergo an invasive cardiopulmonary exercise test to assess changes in hemodynamics and gas exchange during exercise. When coupled with other physiological testing and blood -omic analyses involved in the PVDOMICS study, the comprehensive right heart catheterization protocol described here holds promise to clarify the diagnosis and clustering of pulmonary hypertension patients into cohorts beyond the traditional 5 World Symposium on Pulmonary Hypertension groups. This article will describe the methods applied for invasive hemodynamic characterization in the PVDOMICS program. Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT02980887.

Sex Differences in Cardiometabolic Traits and Determinants of Exercise Capacity in Heart Failure With Preserved Ejection Fraction

Sex differences in heart failure with preserved ejection fraction (HFpEF) have been established, but insights into the mechanistic drivers of these differences are limited. To examine sex differences in cardiometabolic profiles and exercise hemodynamic profiles among individuals with HFpEF. This cross-sectional study was conducted at a single-center tertiary care referral hospital from December 2006 to June 2017 and included 295 participants who met hemodynamic criteria for HFpEF based on invasive cardiopulmonary exercise testing results. We examined sex differences in distinct components of oxygen transport and utilization during exercise using linear and logistic regression models. The data were analyzed from June 2018 to May 2019. Resting and exercise gas exchange and hemodynamic parameters obtained during cardiopulmonary exercise testing. Of 295 participants, 121 (41.0%) were men (mean [SD] age, 64 [12] years) and 174 (59.0%) were women (mean [SD] age, 61 [13] years). Compared with men, women with HFpEF in this tertiary referral cohort had fewer comorbidities, including diabetes, insulin resistance, and hypertension, and a more favorable adipokine profile. Exercise capacity was similar in men and women (percent predicted peak oxygen [O2] consumption: 66% in women vs 68% in men; P = .38), but women had distinct deficits in components of the O2 pathway, including worse biventricular systolic reserve (multivariable-adjusted analyses: ΔLVEF β = -1.70; SE, 0.86; P < .05; ΔRVEF β = -2.39, SE=0.80; P = .003), diastolic reserve (PCWP/CO: β = 0.63; SE, 0.31; P = .04), and peripheral O2 extraction (C(a-v)O2 β=-0.90, SE=0.22; P < .001)). Despite a lower burden of cardiometabolic disease and a similar percent predicted exercise capacity, women with HFpEF demonstrated greater cardiac and extracardiac deficits, including systolic reserve, diastolic reserve, and peripheral O2 extraction. These sex differences in cardiac and skeletal muscle responses to exercise may illuminate the pathophysiology underlying the development of HFpEF and should be investigated further.

Metabolomics of exercise pulmonary hypertension are intermediate between controls and patients with pulmonary arterial hypertension.

Mechanisms underlying pulmonary arterial hypertension (PAH) remain elusive. Pulmonary arterial hypertension and exercise PH share similar physiologic consequences; it is debated whether they share biologic mechanisms and if exercise PH represents an early phase of pulmonary arterial hypertension. We conducted an observational study to test if there is a graded metabolic disturbance along the severity of PH, which may indicate shared or disparate pathophysiology. Individuals referred to an academic medical dyspnea center with unexplained exertional intolerance underwent invasive cardiopulmonary exercise testing. We identified controls with no hemodynamic exercise limitation, individuals with exercise PH (mean pulmonary arterial pressure (mPAP) < 25 mmHg at rest but ≥ 30 mmHg during exercise without pulmonary venous hypertension) and pulmonary arterial hypertension (mPAP > 25 mmHg at rest without pulmonary venous hypertension) (n = 26 in each group). Unbiased metabolomics with chromatography mass spectrometry was performed on pulmonary arterial blood at rest and peak exercise. Random forest analysis and hierarchical clustering were used to quantify metabolite prediction of group membership and rank metabolites which were significantly different between groups. Compared to controls, pulmonary arterial hypertension subjects exhibited perturbations in pathways involving glycolysis, TCA cycle, fatty acid and complex lipid oxidation, collagen deposition and fibrosis, nucleotide metabolism, and others. The metabolic signature of exercise PH was uniquely between that of control and pulmonary arterial hypertension subjects. Accuracy predicting control, exercise PH, and pulmonary arterial hypertension group was 96%, 90%, and 88%, respectively, using paired rest-exercise metabolic changes. Our data suggest the metabolic profile of exercise PH is between that of controls and patients with pulmonary arterial hypertension.

P323Haemodynamic implications of mitral regurgitation in heart failure with preserved ejection fraction

Abstract Background Mild to moderate mitral regurgitation (MR) is a common finding in heart failure with preserved ejection fraction (HFpEF). MR is often considered to be an innocent bystander, yet little data is available regarding its implications. Aim Determine the pathophysiologic correlates of MR in HFpEF Methods We retrospectively studied 280 patients with invasively proven HFpEF. MR was absent (None or trivial) in 163 subjects (Non-MR-HFpEF), and present in 117 (MR-HFpEF; 78 mild and 39 moderate MR). 247 subjects also underwent invasive cardiopulmonary exercise testing. Results At rest, MR-HFpEF subjects displayed higher pulmonary artery pressures (PAP), PCWP, and pulmonary vascular resistance (PVR; Table). During exercise, PAP and PCWP were not significantly different among groups, but MR-HFpEF displayed reduced ability to enhance cardiac output (CO) in response to heightened metabolic demand (oxygen consumption, VO2; Figure). Baseline characteristics and haemodynamic characterization at baseline and peak exercise Baseline characteristics Non-MR-HFpEF (N=163) MR-HFpEF (N=117) p value Age 66±11 71±10 0.0002 Female (%) 56 69 0.02 AFib (%) 13 38 &lt;0.0001 Nt proBNP 192 [66, 557] 870 [401, 2135] &lt;0.0001 E/E' 12.3±5.5 15.6±7.2 0.0006 LVEF (%) 64±6 62±6 0.0001 RV fractional area change (%) 51±9 47±10 0.0001 Mean PA (mmHg) 25±7 28±9 0.001 Mean PCWP (mmHg) 15±5 17±6 0.0002 PVR (Woods) 2.0±1.1 2.5±1.4 0.015 CO (L/min) 5.5±1.6 4.8±1.3 0.12 Peak exercise hemodynamics Non-MR-HFpEF (N=152) MR-HFpEF (N=95) p value Mean PA (mmHg 45±10 46.5±10 0.07 Mean PCWP (mmHg) 32±6 31±6 0.6 PVR (Woods) 1.8±1.6 2.7±2.4 0.002 CO (L/min) 9.1±3 7.2±3 0.01 P value adjusted for age, gender and BMI. CO change in response to VO2 increase Conclusion The presence of even mild MR in HFpEF is associated with more adverse hemodynamics, greater pulmonary vascular dysfunction and impaired CO reserve with exercise. Further study is required to better understand the natural history and treatment for MR in HFpEF. Acknowledgement/Funding None

Unexplained exertional intolerance associated with impaired systemic oxygen extraction.

The clinical investigation of exertional intolerance generally focuses on cardiopulmonary diseases, while peripheral factors are often overlooked. We hypothesize that a subset of patients exists whose predominant exercise limitation is due to abnormal systemic oxygen extraction (SOE). We reviewed invasive cardiopulmonary exercise test (iCPET) results of 313 consecutive patients presenting with unexplained exertional intolerance. An exercise limit due to poor SOE was defined as peak exercise (Ca-vO2)/[Hb] ≤ 0.8 and VO2max < 80% predicted in the absence of a cardiac or pulmonary mechanical limit. Those with peak (Ca-vO2)/[Hb] > 0.8, VO2max ≥ 80%, and no cardiac or pulmonary limit were considered otherwise normal. The otherwise normal group was divided into hyperventilators (HV) and normals (NL). Hyperventilation was defined as peak PaCO2 < [1.5 × HCO3 + 6]. Prevalence of impaired SOE as the sole cause of exertional intolerance was 12.5% (32/257). At peak exercise, poor SOE and HV had less acidemic arterial blood compared to NL (pHa = 7.39 ± 0.05 vs. 7.38 ± 0.05 vs. 7.32 ± 0.02, p < 0.001), which was explained by relative hypocapnia (PaCO2 = 29.9 ± 5.4mmHg vs. 31.6 ± 5.4 vs. 37.5 ± 3.4, p < 0.001). For a subset of poor SOE, this relative alkalemia, also seen in mixed venous blood, was associated with a normal PvO2 nadir (28 ± 2mmHg vs. 26 ± 4, p = 0.627) but increased SvO2 at peak exercise (44.1 ± 5.2% vs. 31.4 ± 7.0, p < 0.001). We identified a cohort of patients whose exercise limitation is due only to systemic oxygen extraction, due to either an intrinsic abnormality of skeletal muscle mitochondrion, limb muscle microcirculatory dysregulation, or hyperventilation and left shift the oxyhemoglobin dissociation curve.

Tools of the Trade: How Do You Perform and Interpret an Exercise Test?

Background: Most pulmonary vascular disease (PVD) is poorly modifiable and incurable even with effective therapy. Therefore, adaptation to stress, the reserve of the cardiopulmonary system, is important for assessment of patient function and prognosis. Methods that assess the adaptation to stress, especially exercise, provide valuable insight into diagnosis, prognosis, and response to therapy.Implications for Clinicians: We provide a comprehensive review of the indications, methodology, and interpretation, as well as practical information of the forms of provocative testing in PVD. We include 6-minute walk testing, noninvasive cardiopulmonary exercise testing (CPET), invasive CPET, and additional forms, including volume loading.Conclusions: Through a clear understanding of the methodology in the assessment of PVD, the clinician can determine which of these “tools of the trade” are best suited to the individual patient and situation.

Dynamic right ventricular-pulmonary arterial uncoupling during maximum incremental exercise in exercise pulmonary hypertension and pulmonary arterial hypertension.

Despite recent advances, the prognosis of pulmonary hypertension (PH) remains poor. While the initial insult in PH implicates the pulmonary vasculature, the functional state, exercise capacity, and survival of such patients are closely linked to right ventricular (RV) function. In the current study, we sought to investigate the effects of maximum incremental exercise on the matching of RV contractility and afterload (i.e. right ventricular–pulmonary arterial [RV–PA] coupling) in patients with exercise PH (ePH) and pulmonary arterial hypertension (PAH). End-systolic elastance (Ees), pulmonary arterial elastance (Ea), and RV–PA coupling (Ees/Ea) were determined using single-beat pressure-volume loop analysis in 40 patients that underwent maximum invasive cardiopulmonary exercise testing. Eleven patients had ePH, nine had PAH, and 20 were age-matched controls. During exercise, the impaired exertional contractile reserve in PAH was associated with blunted stroke volume index (SVI) augmentation and reduced peak oxygen consumption (peak VO2 %predicted). Compared to PAH, ePH demonstrated increased RV contractility in response to increasing RV afterload during exercise; however, this was insufficient and resulted in reduced peak RV–PA coupling. The dynamic RV–PA uncoupling in ePH was associated with similarly blunted SVI augmentation and peak VO2 as PAH. In conclusion, dynamic rest-to-peak exercise RV–PA uncoupling during maximum exercise blunts SV increase and reduces exercise capacity in exercise PH and PAH. In ePH, the insufficient increase in RV contractility to compensate for increasing RV afterload during maximum exercise leads to deterioration of RV–PA coupling. These data provide evidence that even in the early stages of PH, RV function is compromised.

Early histological changes of pulmonary arterial hypertension disclosed by invasive cardiopulmonary exercise testing.

Early diagnosis of pulmonary artery hypertension (PAH) is diagnostically challenging given the extent of pulmonary vascular remodeling required to bring about clinical signs and symptoms. Exercise testing can be invaluable in this setting, as stressing the cardiopulmonary system may unmask early disease. This report describes a young patient with a positive family history of PAH in whom contemporaneous invasive cardiopulmonary exercise testing and surgical lung biopsy reveal the novel association between exercise pulmonary hypertension (ePH) and early histological changes of PAH. Exercise PH currently carries no pathological correlates which means the hemodynamic effects of early pulmonary vascular remodeling remain unknown. Following the recent proceedings from the World Symposium in Pulmonary Hypertension 2018, which broaden the hemodynamic definition of PAH, this report suggests an important association between ePH and early pulmonary vascular remodeling supporting a role for exercise hemodynamic evaluation in patients at increased familial risk of PAH.

Left atrial strain and compliance in the diagnostic evaluation of heart failure with preserved ejection fraction.

Left atrial (LA) function is impaired in heart failure with preserved ejection fraction (HFpEF) and predicts disease severity and risk of adverse outcome. We sought to evaluate whether LA strain could enhance diagnosis of HFpEF. Consecutive patients with unexplained exertional dyspnoea and image quality suitable for measuring LA strain underwent invasive cardiopulmonary exercise testing to ascertain the presence of HFpEF or non-cardiac causes of dyspnoea (NCD). LA reservoir strain was measured in all patients, while LA conduit and booster strain were measured in patients with sinus rhythm. LA strain was measurable in 363 of 378 examinations (96.5%; HFpEF: 238, NCD: 125). LA reservoir strain (29 ± 16% vs. 40 ± 13%, P<0.0001) and conduit strain (18 ±10% vs. 22 ±10%, P=0.0001) were significantly impaired in HFpEF compared to NCD. Of all echocardiographic indices, LA reservoir strain best discriminated HFpEF from NCD [area under the curve (AUC) 0.719, P<0.0001], outperforming E/e' (AUC difference +0.117, P<0.0001), LA enlargement (+0.090, P=0.001), tricuspid regurgitation velocity >2.8m/s (+0.082, P=0.0085), left ventricular hypertrophy (+0.0159, P<0.0001) and left ventricular global longitudinal strain (+0.0198, P<0.0001). Indexing LA reservoir strain to estimated LA pressure (E/e') as a surrogate for LA compliance further improved diagnostic performance (AUC 0.772, P<0.0001; +0.053 compared to LA reservoir strain alone, P=0.003). Left atrial reservoir strain may provide enhanced diagnostic accuracy beyond conventional echocardiographic measures to discriminate HFpEF from NCD. Further study is required to verify the diagnostic utility of LA strain.

Rest ETCO2 and VE/VCO2 are Superior to Exercise Gas Exchange Parameters with Invasive Cardiopulmonary Exercise Testing to Predict Pulmonary Vascular Disease in Patients with Dyspnea of Unclear Etiology

Purpose We sought to predict exercise-induced pulmonary hypertension (PH) and behavior of resting PH with exercise with gas exchange parameters. Methods We reviewed clinical, echocardiographic and invasive cardiopulmonary exercise testing data for 75 consecutive patients with unexplained dyspnea . Results Among the overall cohort, mean age (± SD) was 58.9±14.5 years. Based on the final diagnosis and physiological phenotype, we divided the overall cohort into three groups: pulmonary vascular disease (PVD) - combination of WHO group I/III/IV (n=23, 30%), pulmonary venous hypertension - WHO group II (n=38, 52%) and the control group with no PH (n=14, 19%). Echocardiographic parameters among PVD vs PVH vs Control group: right ventricle (RV): left ventricle ratio 0.9±0.2 vs 0.9±.02 vs 0.8±0.2, tricuspid annular pan-systolic excursion 17±5 vs 20±5 vs 21±3 mm, RV outflow tract acceleration time 98±17 vs 107±23 vs 124±23 m.sec, while other rest -> exercise parameters are in Figure 1. Among different gas exchange parameters, rest ETCO 2 and VE/VCO2 had the highest predictive ability on ROC analysis to identify both rest and exercise PVR > 3 WU, and PVD (vs non-PVD diagnosis) with AUC: 0.81-0.82 range. Based on these findings, we created a simple easy-to-use gas exchange scoring system with rest ETCO2 and VE/VCO2 that can help identify patients with pulmonary vascular disease (Figure 2). Conclusion In dyspnea of unclear etiology, rest gas exchange parameters (ETCO2 and VE/VCO2) can identify pulmonary vascular disease as the cause.

Association between lung ultrasound findings and invasive exercise haemodynamics in patients with undifferentiated dyspnoea.

AimsDyspnoea is common in heart failure (HF) but non‐specific. Lung ultrasound (LUS) could represent a non‐invasive tool to detect subclinical pulmonary congestion in patients with undifferentiated dyspnoea.Methods and resultsWe assessed the feasibility of an abbreviated LUS protocol (eight and two zones) in a prospective pilot study of 25 ambulatory patients with undifferentiated dyspnoea undergoing clinically indicated invasive cardiopulmonary exercise testing (iCPET) at rest (LUS 1) and after peak exercise (LUS 2). We also related LUS findings (B‐lines) to invasive haemodynamics stratified by supine pulmonary capillary wedge pressure (PCWP) (Congestion, >15 mmHg; Control, ≤15 mmHg). All enrolled patients (median age 68, 60% women, 32% prior HF, median ejection fraction 59%) had interpretable LUS 1 images in eight zones, and 20 (80%) had adequate LUS 2 images. LUS images were adequate in two posterior zones in 24 patients (96%) for LUS 1 and 18 (72%) for LUS 2. Although B‐line number was numerically higher in the Congestion group at rest and after peak exercise, this difference did not reach statistical significance. In the entire cohort, there was an association between B‐lines and rest systolic pulmonary artery pressure (r = 0.46, P = 0.02) and PCWP (r = 0.54, P = 0.005). There was an inverse relationship between B‐lines and peak VO2 (r = −0.65, P = 0.002).ConclusionsAmong ambulatory patients with undifferentiated dyspnoea, an abbreviated LUS protocol before and after iCPET is feasible in the majority of patients. B‐line number at rest was associated with invasively measured markers of haemodynamic congestion and was inversely related with peak VO2.

Clinical application of invasive cardiopulmonary exercise test for dyspnea diagnosis in Chinese people.

Dyspnea is a common clinical manifestation of subjective sensation and objective signs of breathless. There are multiple organic dysfunction or non-organic causes which may lead to dyspnea.

Approach to the Patient with Dyspnea

Dyspnea is a common, distressing symptom of cardiopulmonary and neuromuscular disease. In a consensus statement, the American Thoracic Society defined dyspnea as “a subjective experience of breathing discomfort that consists of qualitatively distinct sensations that vary in intensity.” Dyspnea is a nonspecific complaint and is one of the most frequent patient complaints. This review discusses the definition, epidemiology, etiology, pathophysiology, peripheral mechanisms, and evaluation of dyspnea. Figures depict cellular metabolism and exercise physiology, and an invasive cardiopulmonary exercise testing (iCPET) flow diagram. Tables list the common causes of dyspnea, invasive cardiopulmonary exercise testing (iCPET) diagnosis, and iCPET characteristics of pulmonary hypertension. This review contains 2 highly rendered figures, 3 tables, and 51 references.