Background Exercise limitation in chronic obstructive pulmonary disease (COPD) is commonly attributed to abnormal ventilatory mechanics and/or skeletal muscle function, while cardiovascular contributions remain relatively understudied. To date, the integrative exercise responses associated with different cardiopulmonary exercise limitation phenotypes in COPD have not been explored but may provide novel therapeutic utility. This study determined the ventilatory, cardiovascular, and metabolic responses to incremental exercise in patients with COPD with different exercise limitation phenotypes. Methods Patients with COPD (n = 95, FEV1:23–113%pred) performed a pulmonary function test and incremental cardiopulmonary exercise test. Exercise limitation phenotypes were classified as: ventilatory [peak ventilation (VEpeak)/maximal ventilatory capacity (MVC) ≥ 85% or MVC-VEpeak ≤ 11 L/min, and peak heart rate (HRpeak) < 90%pred], cardiovascular (VEpeak/MVC < 85% or MVC-VEpeak > 11 L/min, and HRpeak ≥ 90%pred), or combined (VEpeak/MVC ≥ 85% or MVC-VEpeak ≤ 11 L/min, and HRpeak ≥ 90%pred). Results FEV1 varied within phenotype: ventilatory (23–75%pred), combined (28–90%pred), and cardiovascular (68–113%pred). The cardiovascular phenotype had less static hyperinflation, a lower end-expiratory lung volume and larger tidal volume at peak exercise compared to both other phenotypes (p < 0.01 for all). The cardiovascular phenotype reached a higher VEpeak (60.8 ± 11.5 L/min vs. 45.3 ± 15.5 L/min, p = 0.002), cardiopulmonary fitness (VO2peak: 20.6 ± 4.0 ml/kg/min vs. 15.2 ± 3.3 ml/kg/min, p < 0.001), and maximum workload (103 ± 34 W vs. 72 ± 27 W, p < 0.01) vs. the ventilatory phenotype, but was similar to the combined phenotype. Conclusion Distinct exercise limitation phenotypes were identified in COPD that were not solely dependent upon airflow limitation severity. Approximately 50% of patients reached maximal heart rate, indicating that peak cardiac output and convective O2 delivery contributed to exercise limitation. Categorizing patients with COPD phenotypically may aid in optimizing exercise prescription for rehabilitative purposes.

BACKGROUND Pulmonary hypertension (PH) is a state of high afterload to the right ventricle (RV), which is described as afterload sensitive. The purpose of this study was to examine the effect of exercise on the relationship between RV systolic performance [measured as end-systolic elastance (Ees)], and RV afterload [measured as pulmonary arterial (PA) elastance (Ea)] between 2 groups of patients with pulmonary arterial hypertension (PAH) or PH due to left heart disease (PH-LHD). METHODS AND RESULTS Patients with suspected PH underwent right heart catheterization with cycle-ergometry and classified by their exercise hemodynamic responses: 1) Normal 2) PAH and 3) PH-LHD. RV, right atrium (RA), and PA pressures were recorded continuously and analyzed offline. As our lab previously reported, RV Ees and PA Ea were calculated using the single-beat method, and Ees:Ea ratio expresses RV-PA coupling. Ees:Ea is defined as uncoupled if < 0.8. Results were analyzed at semi-upright rest and exercise. Data is presented as Mean ± SD or Median [25th – 75th Percentiles]. We included 40 patients (35%Female; 58±15 years); exercise hemodynamic classification comprised 18 Normal, 11 PAH, and 11 PH-LHD. At rest Ea and Ees were significantly elevated in PAH (0.45[0.38-0.98], p=0.002 and 0.85[0.65-1.20], p=0.003) and PH-LHD (0.51[0.32-0.67], p=0.001 and 0.74[0.39-1.20], p=0.017) vs. Normal (0.22[0.17-0.27] and 0.41[0.29-0.54]). Ea increased significantly with exercise in PAH (0.60[0.51-1.36], p=0.003) and PH-LHD (0.59[0.37-0.91], p=0.002) compared to Normal (0.29[0.21-0.36]). Exercise was associated with a significant decline in Ees:Ea ratio in PH-LHD (∆-0.23±0.72, p=0.022). Ees:Ea ratio was uncoupled at rest/exercise in 6% of the Normal group, 55% of the PAH group and 36% of the PH-LHD group. Figure 1 illustrates the trend to Ees:Ea uncoupling if Ea increased by more than 0.2mmHg/mL. Compared to patients with preserved Ees:Ea coupling, patients with PH and Ees:Ea uncoupling with exercise demonstrated significantly higher increases in RA pressures (∆9±5mmHg vs ∆4±3mmHg, p=0.012) and more impaired stroke volume indexed to body surface area (∆3±9mL/m2 vs ∆12±8mL/m2 p=0.032). CONCLUSION During exercise, RV afterload increases in patients with PAH and PH-LHD. In both PH groups, the proportion of patients with Ees:Ea uncoupling was high, and the decline in Ees:Ea ratio reached statistical significance in PH-LHD. Uncoupling of the Ees:Ea ratio occurred with larger increases in Ea and was associated with evidence of impaired RV systolic and diastolic function with exercise. Limiting the increase in Ea with exercise and/or preservation of Ees:Ea coupling may optimize RV function in PH patients. Pulmonary hypertension (PH) is a state of high afterload to the right ventricle (RV), which is described as afterload sensitive. The purpose of this study was to examine the effect of exercise on the relationship between RV systolic performance [measured as end-systolic elastance (Ees)], and RV afterload [measured as pulmonary arterial (PA) elastance (Ea)] between 2 groups of patients with pulmonary arterial hypertension (PAH) or PH due to left heart disease (PH-LHD). Patients with suspected PH underwent right heart catheterization with cycle-ergometry and classified by their exercise hemodynamic responses: 1) Normal 2) PAH and 3) PH-LHD. RV, right atrium (RA), and PA pressures were recorded continuously and analyzed offline. As our lab previously reported, RV Ees and PA Ea were calculated using the single-beat method, and Ees:Ea ratio expresses RV-PA coupling. Ees:Ea is defined as uncoupled if < 0.8. Results were analyzed at semi-upright rest and exercise. Data is presented as Mean ± SD or Median [25th – 75th Percentiles]. We included 40 patients (35%Female; 58±15 years); exercise hemodynamic classification comprised 18 Normal, 11 PAH, and 11 PH-LHD. At rest Ea and Ees were significantly elevated in PAH (0.45[0.38-0.98], p=0.002 and 0.85[0.65-1.20], p=0.003) and PH-LHD (0.51[0.32-0.67], p=0.001 and 0.74[0.39-1.20], p=0.017) vs. Normal (0.22[0.17-0.27] and 0.41[0.29-0.54]). Ea increased significantly with exercise in PAH (0.60[0.51-1.36], p=0.003) and PH-LHD (0.59[0.37-0.91], p=0.002) compared to Normal (0.29[0.21-0.36]). Exercise was associated with a significant decline in Ees:Ea ratio in PH-LHD (∆-0.23±0.72, p=0.022). Ees:Ea ratio was uncoupled at rest/exercise in 6% of the Normal group, 55% of the PAH group and 36% of the PH-LHD group. Figure 1 illustrates the trend to Ees:Ea uncoupling if Ea increased by more than 0.2mmHg/mL. Compared to patients with preserved Ees:Ea coupling, patients with PH and Ees:Ea uncoupling with exercise demonstrated significantly higher increases in RA pressures (∆9±5mmHg vs ∆4±3mmHg, p=0.012) and more impaired stroke volume indexed to body surface area (∆3±9mL/m2 vs ∆12±8mL/m2 p=0.032). During exercise, RV afterload increases in patients with PAH and PH-LHD. In both PH groups, the proportion of patients with Ees:Ea uncoupling was high, and the decline in Ees:Ea ratio reached statistical significance in PH-LHD. Uncoupling of the Ees:Ea ratio occurred with larger increases in Ea and was associated with evidence of impaired RV systolic and diastolic function with exercise. Limiting the increase in Ea with exercise and/or preservation of Ees:Ea coupling may optimize RV function in PH patients.

In healthy younger adults, combined dynamic hyperinflation (DH) and negative intrathoracic pressures (nITP) attenuate left ventricular filling, but through different mechanisms at different severities. DH and nITP contribute to increased left ventricular afterload through mechanical effects in addition to presumed reflexive regulation, which can be further increased by elevated arterial loading. However, within this demographic, the left ventricle has substantial reserve to increase systolic performance, which matches contractility to afterload to preserve stroke volume.

BACKGROUND Current guidelines require patients with heart failure (HF) being evaluated for advanced therapies such as heart transplantation or left ventricular assist device (LVAD) implantation to undergo right heart catheterization to identify the presence of pulmonary hypertension (PH). PH that is irreversible is a relative contraindication to heart transplantation and associated with poor prognosis. Based on the International Society for Heart and Lung Transplantation guidelines, reversibility is assessed with a vasodilator challenge if pulmonary artery systolic pressure (PASP) is > 50 mmHg, and either transpulmonary gradient (TPG) is > 15 mmHg or pulmonary vascular resistance (PVR) is > 3 WU. However, the most updated 6th World Symposium on Pulmonary Hypertension defined PH more broadly as to mean pulmonary artery pressure (mPAP) > 20 mmHg. As such, there is an intermediate group of patients with mild PH not meeting the threshold to receive a vasodilator challenge to determine whether mild PH is reversible. Our aim was to assess the hemodynamic characteristics of this group and determine whether they are at risk of worse clinical outcomes. METHODS AND RESULTS A retrospective analysis was performed of 175 patients with heart failure who were referred to our centre for right heart catheterization as part of evaluation for candidacy for advanced heart failure therapies. Patients were divided into three groups based on initial hemodynamics: patients with mPAP < 20 mmHg (No-PH, n=57), patients with significant PH meeting current guideline criteria for a vasodilator challenge (PH+V, n=41) and patients with mPAP > 20 mmHg that did not meet the threshold for vasodilator challenge (PH-V, n=77). Compared to the No-PH group, the PH-V group did not have a significantly different stroke volume index or cardiac index, however, they had a significantly higher PVR, indicating greater resistive load, and lower pulmonary artery compliance (PAC), indicating higher pulsatile load (Table). The PH-V group also had significantly higher mean right atrial pressure (mRAP) compared to the No-PH group, suggesting right ventricular decompensation. Composite pre-and post-intervention three-year survival after catheterization appeared lower in both PH+V and PH-V patients compared to the No-PH group (Figure). CONCLUSION HF patients assessed for advanced therapies identified as having mild PH have increased pulmonary pulsatile and resistive load, along with elevated right-sided filling pressures, and have increased mortality. Currently, this group does not undergo vasodilator testing to determine PH reversibility. Whether mild PH is modifiable, and its relationship to outcomes after heart transplantation or LVAD implant requires further study. Current guidelines require patients with heart failure (HF) being evaluated for advanced therapies such as heart transplantation or left ventricular assist device (LVAD) implantation to undergo right heart catheterization to identify the presence of pulmonary hypertension (PH). PH that is irreversible is a relative contraindication to heart transplantation and associated with poor prognosis. Based on the International Society for Heart and Lung Transplantation guidelines, reversibility is assessed with a vasodilator challenge if pulmonary artery systolic pressure (PASP) is > 50 mmHg, and either transpulmonary gradient (TPG) is > 15 mmHg or pulmonary vascular resistance (PVR) is > 3 WU. However, the most updated 6th World Symposium on Pulmonary Hypertension defined PH more broadly as to mean pulmonary artery pressure (mPAP) > 20 mmHg. As such, there is an intermediate group of patients with mild PH not meeting the threshold to receive a vasodilator challenge to determine whether mild PH is reversible. Our aim was to assess the hemodynamic characteristics of this group and determine whether they are at risk of worse clinical outcomes. A retrospective analysis was performed of 175 patients with heart failure who were referred to our centre for right heart catheterization as part of evaluation for candidacy for advanced heart failure therapies. Patients were divided into three groups based on initial hemodynamics: patients with mPAP < 20 mmHg (No-PH, n=57), patients with significant PH meeting current guideline criteria for a vasodilator challenge (PH+V, n=41) and patients with mPAP > 20 mmHg that did not meet the threshold for vasodilator challenge (PH-V, n=77). Compared to the No-PH group, the PH-V group did not have a significantly different stroke volume index or cardiac index, however, they had a significantly higher PVR, indicating greater resistive load, and lower pulmonary artery compliance (PAC), indicating higher pulsatile load (Table). The PH-V group also had significantly higher mean right atrial pressure (mRAP) compared to the No-PH group, suggesting right ventricular decompensation. Composite pre-and post-intervention three-year survival after catheterization appeared lower in both PH+V and PH-V patients compared to the No-PH group (Figure). HF patients assessed for advanced therapies identified as having mild PH have increased pulmonary pulsatile and resistive load, along with elevated right-sided filling pressures, and have increased mortality. Currently, this group does not undergo vasodilator testing to determine PH reversibility. Whether mild PH is modifiable, and its relationship to outcomes after heart transplantation or LVAD implant requires further study.

Purpose In healthy humans, pulmonary artery pressures (PAP) increase modestly and equilibrate rapidly in response to constant intensity exercise. PAP increase markedly in pre- or post-capillary pulmonary hypertension (pre-cap or post-cap PH), but the time course is unclear. We studied pulse (PP) and diastolic (PADP) PAP as indices of pulsatile load and pulmonary vascular outflow pressure, respectively, and explored whether the magnitude and time course of their response to exercise differs in pre-cap or post-cap PH. Methods Patients underwent right heart catheterization with cycle-ergometry (25/40W, F/M), and were classified by their exercise hemodynamic responses: 1) Normal 2) pre-cap PH and 3) post-cap PH. PAP were recorded continuously and analyzed offline. Changes from Control, 2 min, and 7 min were examined. Results We studied 76 patients (47% F; 59±15 years); groups comprised 32 Normal, 22 pre-cap PH, and 22 post-cap PH. After exercise onset in the Normal group, PADP increased at 2 min (∆5±3mmHg). This increase was less than both pre-cap PH (∆9±4mmHg, p<0.01) and post-cap PH (∆8±6mmHg, p=0.1), which did not differ (p=0.99). While PADP did not increase further at 7 min in Normal and post-cap PH groups, it did in the pre-cap PH group (∆3±5mmHg, p=0.04, Fig. 1). In the Normal group, PP increased at 2 min (∆5±4mmHg). PP increases at 2 min were greater in pre-cap PH (∆13±8mmHg) than post-cap PH (∆7±4mmHg, p<0.01) and Normal (p<0.01). Although PP increased further at 7 min in the Normal group (∆2±3mmHg, p<0.01), the increases in pre-cap PH (∆6±5mmHg, p<0.01) and post-cap PH (∆6±6mmHg, p<0.01) were both greater compared to Normal (pre-cap PH: p<0.01 post-cap PH: p=0.02, Fig. 1). Conclusion During exercise, patients with pre-cap or post-cap PH demonstrate differences in both the magnitude and temporality of change in PAP. Despite constant work-rate, the pulmonary vascular load continues to increase in both pre-cap and post-cap PH.

This chapter explores how quality is assessed in craft beer through describing tastes and aromas in relationship to categories of beer style. Drawing on documentary sources, it explores the development and formalisation of definitions of beer styles, and the development of the contemporary language used to describe and assess taste. It then ethnographically explores how these are combined in the practice of craft beer judging at a competition through a novel assemblage of different methods. The empirical work contributes novel methods for exploring tasting practices, detailed ethnographic description of beer judging and an exploration of how the organisation of style guides and taste descriptions have contributed to defining and assessing quality in craft beer.

With each heartbeat, the right ventricle (RV) inputs blood into the pulmonary vascular (PV) compartment, which conducts blood through the lungs at low pressure and concurrently fills the left atrium (LA) for output to the systemic circulation. This overall hemodynamic function of the integrated RV-PV-LA unit is determined by complex interactions between the components that vary over the cardiac cycle but are often assessed in terms of mean pressure and flow. Exercise challenges these hemodynamic interactions as cardiac filling increases, stroke volume augments, and cycle length decreases, with PV pressures ultimately increasing in association with cardiac output. Recent cardiopulmonary exercise hemodynamic studies have enriched the available data from healthy adults, yielded insight into the underlying mechanisms that modify the PV pressure-flow relationship, and better delineated the normal limits of healthy responses to exercise. This review will examine hemodynamic function of the RV-PV-LA unit using the two-element Windkessel model for the pulmonary circulation. It will focus on acute PV and LA responses that accommodate increased RV output during exercise, including PV recruitment and distension and LA reservoir expansion, and the integrated mean pressure-flow response to exercise in healthy adults. Finally, it will consider how these responses may be impacted by age-related remodeling and modified by sex-related cardiopulmonary differences. Studying the determinants and recognizing the normal limits of PV pressure-flow relations during exercise will improve our understanding of cardiopulmonary mechanisms that facilitate or limit exercise.

Among dyspneic patients, we identified abnormal exercise phenotypes based upon ΔmPAP/ΔCO, ΔPAWP/ΔCO, and PP/PAWP responses. Our study refines quantitative classification of abnormal exercise hemodynamic phenotypes based on an improved understanding of the interrelationship between left heart filling pressure and pulmonary vascular behaviour.

Purpose Exercise during right heart catheterization (RHC) is employed in select centers to demonstrate the extent to which pulmonary artery (PA) hemodynamics and/or left heart filling pressures may be abnormal. We examined right ventricular (RV) end-systolic elastance (Ees), effective PA elastance (Ea), and their coupling (Ees:Ea) at rest and during exercise in patients with dyspnea and/or suspected pulmonary hypertension. Methods Patients referred for an exercise hemodynamic study performed submaximal cycle-ergometry during RHC. We transduced RV and PA pressures simultaneously, and measured thermodilution cardiac output. We determined Ees using the single-beat method and calculated Ea from the ratio of PA pressure to stroke volume. Exercise hemodynamic classifications defined a priori include: 1) left heart disease (Ex-LHD) based on an increased slope of the PA wedge pressure/cardiac output relationship; 2) pulmonary vascular disease (Ex-PVD) based on an elevated end-diastolic pressure gradient; 3) combined (Ex-CPH) if both criteria are met; 4) hemodynamically Ex-Normal if neither criteria are met. Results Preliminary data were available for 54 patients (50% male; Age = 59 ± 14); exercise hemodynamic classifications comprised 23 Ex-Normal, 14 Ex-LHD, 12 Ex-PVD, and 5 Ex-CPH. At rest, Ees was similar in Ex-Normal, Ex-LHD, and Ex-PVD; Ea was higher in Ex-LHD and Ex-PVD compared to Ex-Normal (p<0.01), and so the Ees:Ea ratio was lower (p<0.01). With exercise, in Ex-Normal, Ees remained stable, Ea increased modestly (p<0.01) and the Ees:Ea ratio was preserved. In Ex-LHD, Ees and Ea both increased (p<0.05), and the Ees:Ea ratio was preserved. In Ex-PVD, Ees remained stable as Ea increased (p<0.01), and the Ees:Ea ratio trended modestly down (Fig. 1) Conclusion In patients with pulmonary vascular and/or left heart disease, ventricular-vascular coupling is less favorable than in patients with normal hemodynamics, and abnormalities persist during exercise. Exercise during right heart catheterization (RHC) is employed in select centers to demonstrate the extent to which pulmonary artery (PA) hemodynamics and/or left heart filling pressures may be abnormal. We examined right ventricular (RV) end-systolic elastance (Ees), effective PA elastance (Ea), and their coupling (Ees:Ea) at rest and during exercise in patients with dyspnea and/or suspected pulmonary hypertension. Patients referred for an exercise hemodynamic study performed submaximal cycle-ergometry during RHC. We transduced RV and PA pressures simultaneously, and measured thermodilution cardiac output. We determined Ees using the single-beat method and calculated Ea from the ratio of PA pressure to stroke volume. Exercise hemodynamic classifications defined a priori include: 1) left heart disease (Ex-LHD) based on an increased slope of the PA wedge pressure/cardiac output relationship; 2) pulmonary vascular disease (Ex-PVD) based on an elevated end-diastolic pressure gradient; 3) combined (Ex-CPH) if both criteria are met; 4) hemodynamically Ex-Normal if neither criteria are met. Preliminary data were available for 54 patients (50% male; Age = 59 ± 14); exercise hemodynamic classifications comprised 23 Ex-Normal, 14 Ex-LHD, 12 Ex-PVD, and 5 Ex-CPH. At rest, Ees was similar in Ex-Normal, Ex-LHD, and Ex-PVD; Ea was higher in Ex-LHD and Ex-PVD compared to Ex-Normal (p<0.01), and so the Ees:Ea ratio was lower (p<0.01). With exercise, in Ex-Normal, Ees remained stable, Ea increased modestly (p<0.01) and the Ees:Ea ratio was preserved. In Ex-LHD, Ees and Ea both increased (p<0.05), and the Ees:Ea ratio was preserved. In Ex-PVD, Ees remained stable as Ea increased (p<0.01), and the Ees:Ea ratio trended modestly down (Fig. 1) In patients with pulmonary vascular and/or left heart disease, ventricular-vascular coupling is less favorable than in patients with normal hemodynamics, and abnormalities persist during exercise.

Purpose Acute and chronic right ventricular (RV) dysfunction are common complications experienced by patients with advanced heart failure, particularly after receiving mechanical circulatory support. An elevated right atrial pressure to pulmonary artery wedge pressure ratio (RAP:PAWP) or a reduced pulmonary artery (PA) pulsatility index (PAPI) may identify patients at risk of RV dysfunction. We examined the relationship of these markers to RV end-systolic elastance (Ees), effective PA elastance (Ea), and their coupling ratio (Ees:Ea). Methods We studied patients with advanced heart failure undergoing right heart catheterization to assess cardiac transplant candidacy. We analyzed hemodynamics offline, and calculated both RAP:PAWP and PAPI. We determined RV Ees using the single-beat method and calculated PA Ea from the ratio of PA pressure to stroke volume. We considered cases with either RAP:PAWP >0.63 or PAPI <1.85 to represent RV dysfunction, and values are reported as median (interquartile range). Results Of 165 patients (age = 57 (53-60) years), 42 (25%) met either criteria for RV dysfunction; 33 (20%) had an elevated RAP:PAWP, 24 (15%) had a reduced PAPI, and 15 (9%) had both markers. There were no systematic differences between patients with (n = 42) or without (n = 123) RV dysfunction in terms of age, body mass index, heart rate, or mean arterial pressure. Cardiac index was lower among patients with RV dysfunction (1.8 (1.6-2.0) vs. 2.0 (1.7-2.2) L/min/m2, p = 0.025), as was RV stroke work index (4.6 (3.6-6.0) vs. 8.6 (6.6-11.0) g•m/m2, p < 0.001). Although RV Ees trended modestly lower among patients with RV dysfunction (0.46 (0.33-0.59) vs. 0.55 (0.35-0.69) mmHg/mL, p = 0.09), there were no differences between groups for PA Ea or Ees:Ea (Fig. 1). Conclusion In patients with systolic heart failure being evaluated for advanced therapies, proposed markers of RV dysfunction are modestly associated with load-independent systolic RV performance, but not RV-PA coupling.

Advanced therapies for heart failure with reduced ejection fraction (HFrEF) include cardiac transplantation and mechanical circulatory support. For both therapies, right ventricular (RV) dysfunction and/or pulmonary hypertension portend adverse outcomes, particularly when systolic PA pressure (sPAP) ≥50 mmHg. End-systolic elastance (Ees) quantifies load-independent systolic RV performance, which can be related to the effective PA load (Ea) by their coupling ratio (Ees:Ea). Elastance may be more sensitive than pressures to detect elevated RV afterload and assess RV-PA coupling. We tested the hypothesis that elevated Ea and Ees:Ea uncoupling are associated with worse prognosis in this population. We prospectively enrolled consecutive patients with HFrEF who underwent right heart catheterization as part of their evaluation for advanced therapies into a registry. A sodium nitroprusside challenge was initiated if sPAP ≥50mmHg and either transpulmonary gradient ≥15 mmHg or pulmonary vascular resistance >3 WU. RV and PA pressures were analyzed offline, and Ees and Ea were determined using a single-beat approach. PA Ea >0.5 mmHg/mL was defined as 'elevated', and an Ees:Ea ratio < 0.8 was defined as 'uncoupled'. We retrospectively collected all-cause mortality from electronic patient records, and examined its association with Ees, Ea, and Ees:Ea using Kaplan-Meier analysis and Cox regression adjusted for age and sex. Data are reported as n (%), median [interquartile range], or hazard ratio (HR). We included 175 patients (57 [50-63] years, 77% male) (Table 1). Ea was normal in 65 patients (37%); of these, 14 (22%) demonstrated uncoupled Ees:Ea. Of the 110 (63%) with elevated Ea, 47 had a sPAP ≥50mmHg and 36 (21% overall) met criteria for a vasodilator challenge. For these cases, sodium nitroprusside (0.75 [0.25-1.00] mcg/kg/min) reduced Ea, (0.63 [0.52-0.82] vs. 0.93 [0.83-1.32] mmHg/mL, p < 0.001). Among patients with an elevated Ea, Ees:Ea was uncoupled in 68 (62%) and coupled in 42. Follow-up was available for 164/175 patients. Fifty patients (29%) died over a median follow-up of 2.2 [0.7-4.4] years. Ea (HR = 2.04 (95%CI 1.20-3.48), p = 0.009, χ2 = 6.5) and Ees:Ea (HR = 0.42 (95%CI 0.23-0.76), p = 0.005, χ2 = 13.8) were each associated with mortality, but isolated Ees was not. Mortality was greater in all subgroups compared to patients with normal Ea and coupled Ees:Ea (Figure 1). Elastance measurements identify RV-PA uncoupling, as well as elevated RV afterload in patients with HFrEF even with acceptable PA pressures. Elevated Ea and uncoupled Ees:Ea identify patients with worse prognosis.View Large Image Figure ViewerDownload Hi-res image Download (PPT)

Hemodynamic response to exercise is used to evaluate causes of dyspnea in suspected pulmonary hypertension (PH) related to pulmonary vascular or left heart disease. Such studies may disclose abnormal increases in mean pulmonary artery pressure (mPAP) in the context of cardiac output, even when hemodynamics in the resting state are within normal limits. We hypothesized that the relationship between the pulmonary artery wedge pressure (PAWP) and the pulmonary pulse pressure (PP), closely coupled in health, may further discriminate specific abnormalities of this integrated physiology. The aim of this analysis was to compare changes in the relationship between the PAWP and the PAP during exercise in patients with dyspnea and suspected PH and healthy controls. In this analysis, patients with apparently normal hemodynamics at rest and exercise are presented. In our laboratory, standardized exercise testing during right heart catheterization is performed on a cycle ergometer at submaximal steady state work rates. Healthy controls were previously recruited from the community. Patients with dyspnea and suspected PH were consecutively recruited to participate in a prospective registry. Patients with mPAP < 25mmHg at rest, and a mPAP relative to cardiac output (CO) slope from rest to exercise of < 3WU were included. The pulmonary PP was calculated as the pulmonary artery systolic minus the diastolic pressure. For this analysis, the ratio of the PP to the PAWP was calculated as the primary endpoint (PP:PAWP). The mPAP to CO relationship is demonstrated in 36 healthy controls (Figure 1A) and 85 dyspneic patients (Figure 1B) who underwent hemodynamic exercise testing. Forty-one dyspneic patients met the criteria for inclusion into this portion of the analysis. Hemodynamic variables at rest and exercise are presented in Table 1. There were no significant differences in right atrial, PAPs, PAWP or CO between either group at rest or with exercise. In controls, the histogram distribution demonstrates that the PP:PAWP is similar at rest and with exercise (Figure 1C). In contrast, the histogram distribution demonstrates a proportion of dyspneic patients increase the PP:PAWP with exercise (Figure 1D). 59% of dyspneic patients demonstrated an elevated PP:PAWP during exercise compared to healthy controls, suggesting that the PP was disproportionately elevated in context of the PAWP. Among patients with dyspnea and suspected PH, with apparently normal hemodynamics at rest and with exercise, analysis of the PP:PAWP demonstrate abnormal coupling during exercise in a proportion of this population, which may contribute to symptoms.View Large Image Figure ViewerDownload Hi-res image Download (PPT)

Purpose Provocative testing during right heart catheterization (RHC) is gaining increasing acceptance to evaluate cardiac and pulmonary vascular contributions to dyspnea. For this purpose, the use of cycle ergometry at measured work rates has been recommended as a physiologically relevant and sensitive stressor. Methods The program was initiated in 07/2016. After standard diagnostic RHC, patients were transferred to a cycle ergometer and hemodynamics were assessed in up to 2 exercise stages if tolerated. Hemodynamic diagnoses at rest were assigned based on guideline recommendations and exercise hemodynamic diagnoses were assigned based on sex-specific reference ranges developed by our laboratory. Results Between 07/2016 and 09/2018, 77 patients (60 ± 14 years, 48% female) were referred. Resting hemodynamic assessment was performed in all patients and the exercise protocol was initiated in 74. Figure 1 illustrates the hemodynamic classification at rest and after the exercise protocol. At rest, 47 patients (61%) had normal hemodynamics; after the exercise protocol, the number of patients with normal hemodynamics declined to 26 (34%). Exercise induced pulmonary hypertension related to left heart disease (PH-LHD) was disclosed in 18 (38%) of 47 patients with normal resting hemodynamics. One year follow-up (FUP) assessment has been completed in 19 patients and death or hospitalization was observed in 4 (21%) patients that had 1 year FUP assessment completed and all these adverse outcomes occurred amongst patients with abnormal hemodynamic findings during exercise. Conclusion In this prospective series, a submaximal, cycle ergometry protocol performed during RHC was possible in 96% of the cohort referred. The intervention revealed hemodynamic abnormalities in 45% of patients with normal resting hemodynamics. Amongst patients with normal hemodynamic findings during exercise that had 1 year FUP assessment completed, none had an adverse composite outcome of death or hospitalization.

Exercise during right heart catheterization (RHC) is employed in select centers to demonstrate the extent to which pulmonary artery (PA) hemodynamics and/or left heart filling pressures may be abnormal. Both lesions may increase the effective PA elastance (Ea), which is a measure of afterload to the right ventricle (RV) as it ejects during systole. RV contractile performance can be expressed as the RV end-systolic elastance (Ees), and the ratio of Ees:Ea reflects ventricular-vascular coupling. We examined the Ees:Ea ratio at rest and during exercise in patients with dyspnea and/or suspected pulmonary hypertension, grouped by their exercise hemodynamic classification. Patients referred for an exercise hemodynamic study underwent a submaximal cycle-ergometry challenge during diagnostic RHC. RV and PA pressures were simultaneously transduced, and thermodilution cardiac output was determined. The RV and PA pressure waveforms were analyzed offline to determine Ees using the single-beat method and calculate Ea as [mean PA pressure/stroke volume]. Exercise hemodynamic classifications have been defined a priori by our laboratory from previous prospective studies of exercise hemodynamics in healthy volunteers. Exercise hemodynamic classifications include: 1) left heart disease (Ex-LHD) based on an increased slope of the PA wedge pressure/cardiac output relationship; 2) pulmonary vascular disease (Ex-PVD) based on an elevated end-diastolic pulmonary pressure gradient; 3) combined (Ex-CPH) if both criteria are met; 4) hemodynamically Ex-Normal if neither criteria are met. Preliminary data and descriptive statistics were available for 42 consecutive patients (17M/25F; Age = 58±15); exercise hemodynamic classifications comprised 14 Ex-Normal, 15 Ex-LHD, 8 Ex-PVD, and 5 Ex-CPH. At baseline, mPAP ≥25 mmHg was present in 0/14 Ex-Normal, 5/15 Ex-LHD, 5/8 Ex-PVD, and 5/5 Ex-CPH (Table 1). Ex-LHD had similar Ees and modestly higher Ea compared to Ex-Normal. Ex-PVD had substantially higher Ees and Ea compared to Ex-Normal. Ex-PVD also had substantially higher Ees and Ea compared to Ex-LHD. However, Ees:Ea appeared similarly depressed in both Ex-LHD and Ex-PVD compared to Normal. This was despite normal pulmonary pressures at baseline in Ex-LHD. During exercise, Ees:Ea appeared to augment modestly in Ex-Normal, but remained stable in other groups (Figure 1). Systolic RV performance augmented in proportion with increased load during exercise; however, less favorable ventricular-vascular coupling in patients with pulmonary vascular and/or left heart disease persisted during exercise. Despite mostly normal at rest hemodynamics, ventricular-vascular coupling appears abnormal in patients with left heart disease exposed by exercise.View Large Image Figure ViewerDownload Hi-res image Download (PPT)

Sexual dimorphism has been studied with respect to resting left ventricular (LV) chamber structure and function; however, less is known about other cardiac chambers. The left atrium (LA) functions in continuum with the LV and is thus influenced by its mechanical properties. Both LA structure and function are complex, but examination of LA pressure-volume relationships may provide more comprehensive understanding of the operating characteristics of LA. The objective of this study was to calculate the variables to plot LA pressure-volume coordinates in healthy older adults. Further, we compared the LA operating compliance between men and women and examined the coupling of this mechanical characteristic to pulmonary vascular compliance. Right heart catheterization was performed in healthy men and women in the supine position. Analysis of pulmonary artery wedge pressure (PAWP) tracing was performed to estimate four pressure coordinates corresponding to different phases of the cardiac cycle: ECG QRS complex, A-wave, x'-descent, and V-wave. LA volumes were measured using 2-dimensional echocardiography at four points of the cardiac cycle (bi-plane area-length method): maximal LA volume (LA-Max) at end of T-wave on ECG, preceding atrial contraction (LA-pre-contraction) at beginning of P-wave, minimal LA volume (LA-min) at QRS complex; and LA x'-gated at the frame corresponding to the (A-x') interval after LA-Min. Thus, we identified four pressure-volume coordinates: 1) V-wave, LA-Max; 2) QRS-onset, LA-pre-contraction; 3) A-wave, LA-Min; and 4) x'-descent, x'-gated. LA operating compliance was calculated as [ΔLA volume (V-x')/ΔLA pressure (V-x')], and pulmonary vascular compliance as [stroke volume/pulmonary pulse pressure)]. Thirty-four volunteers (17 men, 17 women) were studied. Right atrial pressure and end-expiratory PAWP were significantly higher in women compared to men. Cardiac index and stroke volume index trended lower in women. There were no differences in LA pressure coordinates, although LA volumes trended lower in women. Pulmonary vascular compliance was significantly higher in men compared to women, although differences were related to body size (Table 1). LA pressure-volume 'loops' based on the four identified coordinates were constructed (Figure 1). There were no differences in LA operating compliance between men and women and this mechanical characteristic was not coupled to pulmonary vascular compliance. LA pressure-volume coordinates can be feasibly constructed from analyses of timed pressure estimates and volume measurements to inform of mechanical properties of LA chamber. LA operating compliance is similar between healthy men and women and not a determinant of pulmonary vascular compliance.View Large Image Figure ViewerDownload Hi-res image Download (PPT)

The importance of right ventricular (RV) function in both health and disease is increasingly recognized, and the 'athletic heart' is of particular interest, in light of recent observations of disproportionate RV remodeling in endurance athletes. RV afterload can be assessed by calculating the pulmonary vascular resistive and pulsatile components, resistance (Rp) and compliance (Cp) respectively. The relationship between Rp and Cp are also affected by the pulmonary artery wedge pressure (PAWP). It has been suggested that pulmonary artery (PA) pressures increase approximately linearly with cardiac output as exercise intensity increases. However, directly-measured pulmonary hemodynamic data to support this hypothesis are sparse. Accordingly, our objective was to directly measure the response of PA hemodynamics to submaximal exercise in endurance-trained athletes. We studied 16 healthy endurance-trained athletes (54±6 years) who underwent exercise right-heart catheterization. PA systolic, diastolic, and mean pressures (PASP, PADP and mPAP, respectively) and PAWP were directly measured. Participants were studied on a semi-upright cycle-ergometer at rest and during consecutive 8-10 minute stages of steady-state exercise at an intensity eliciting heart rates of 100 bpm (EX1), 130 bpm (EX2), and 150 bpm (EX3). Pressure tracings were analyzed offline. PAWP was indexed to work rate (PAWR), and expressed relative to body weight (PAWRwt). We calculated the ratio of the transpulmonary gradient (TPG) to pulmonary pulse pressure (PP) multiplied by R-R interval as an index of steady-flow to pulsatile-flow arterial load (RpCp-time). Pulmonary pressures increased significantly at the onset of exercise, without further rise as exercise intensity progressed (Figure 1). PAWP also increased from CON to EXI with no further change at EX2 and EX3. PAWR and PAWRwt demonstrated a significant decrease from EX1 to EX2 that was sustained for EX3 (Table 1). Despite progressive increases in systemic pulse pressure with increasing exercise intensity, pulmonary pulse pressure rose at EX1 and remained stable through EX2 and EX3. RpCp-time decreased at EX1 without any further change for EX2 and EX3. We observed a remarkably constant PA and PAWP pressure response to increasing submaximal exercise intensity, with a stable change in RpCp-time. These observations in exercise hemodynamics suggest the ability of the PA and pulmonary venous, along with left atrial compartments, to accommodate high conduit flows. These responses appear to limit marked increases in the pulsatile RV afterload during exercise in this population of highly trained, middle-aged endurance athletes.View Large Image Figure ViewerDownload Hi-res image Download (PPT)