Exercise Pulmonary Hypertension Research Articles

Updated Clinical Classification and Hemodynamic Definitions of Pulmonary Hypertension and Its Clinical Implications.

Pulmonary hypertension (PH) refers to a pathologic elevation of the mean pulmonary artery pressure (mPAP) and is associated with increased morbidity and mortality in a wide range of medical conditions. These conditions are classified according to similarities in pathophysiology and management in addition to their invasive hemodynamic profiles. The 2022 ESC/ERS guidelines for the diagnosis and treatment of pulmonary hypertension present the newest clinical classification system and includes significant updates to the hemodynamic definitions. Pulmonary hypertension is now hemodynamically defined as an mPAP > 20 mmHg, reduced from the previous threshold of ≥25 mmHg, due to important insights from both normative and prognostic data. Pulmonary vascular resistance has been extended into the definition of pre-capillary pulmonary hypertension, with an updated threshold of >2 Wood Units (WU), to help differentiate pulmonary vascular disease from other causes of increased mPAP. Exercise pulmonary hypertension has been reintroduced into the hemodynamic definitions and is defined by an mPAP/cardiac output slope of >3 mmHg/L/min between rest and exercise. While these new hemodynamic thresholds will have a significant impact on the diagnosis of pulmonary hypertension, no evidence-based treatments are available for patients with mPAP between 21-24 mmHg and/or PVR between 2-3 WU or with exercise PH. This review highlights the evidence underlying these major changes and their implications on the diagnosis and management of patients with pulmonary hypertension.

MPAP/CO Slope and Oxygen Uptake Add Prognostic Value in Aortic Stenosis.

Recent guidelines redefined exercise pulmonary hypertension as a mean pulmonary artery pressure/cardiac output (mPAP/CO) slope >3 mm Hg·L-1·min-1. A peak systolic pulmonary artery pressure >60 mm Hg during exercise has been associated with an increased risk of cardiovascular death, heart failure rehospitalization, and aortic valve replacement in aortic valve stenosis. The prognostic value of the mPAP/CO slope in aortic valve stenosis remains unknown. In this prospective cohort study, consecutive patients (n=143; age, 73±11 years) with an aortic valve area ≤1.5 cm2 underwent cardiopulmonary exercise testing with echocardiography. They were subsequently evaluated for the occurrence of cardiovascular events (ie, cardiovascular death, heart failure hospitalization, new-onset atrial fibrillation, and aortic valve replacement) during a follow-up period of 1 year. Findings were externally validated (validation cohort, n=141). One cardiovascular death, 32 aortic valve replacements, 9 new-onset atrial fibrillation episodes, and 4 heart failure hospitalizations occurred in the derivation cohort, whereas 5 cardiovascular deaths, 32 aortic valve replacements, 1 new-onset atrial fibrillation episode, and 10 heart failure hospitalizations were observed in the validation cohort. Peak aortic velocity (odds ratio [OR] per SD, 1.48; P=0.036), indexed left atrial volume (OR per SD, 2.15; P=0.001), E/e' at rest (OR per SD, 1.61; P=0.012), mPAP/CO slope (OR per SD, 2.01; P=0.002), and age-, sex-, and height-based predicted peak exercise oxygen uptake (OR per SD, 0.59; P=0.007) were independently associated with cardiovascular events at 1 year, whereas peak systolic pulmonary artery pressure was not (OR per SD, 1.28; P=0.219). Peak Vo2 (percent) and mPAP/CO slope provided incremental prognostic value in addition to indexed left atrial volume and aortic valve area (P<0.001). These results were confirmed in the validation cohort. In moderate and severe aortic valve stenosis, mPAP/CO slope and percent-predicted peak Vo2 were independent predictors of cardiovascular events, whereas peak systolic pulmonary artery pressure was not. In addition to aortic valve area and indexed left atrial volume, percent-predicted peak Vo2 and mPAP/CO slope cumulatively improved risk stratification.

Exercise pulmonary hypertension by the mPAP/CO slope in primary mitral regurgitation.

Exercise-induced pulmonary hypertension (PH), defined by a mean pulmonary arterial pressure over cardiac output (mPAP/CO) slope >3 mmHg/L/min, has important diagnostic and prognostic implications. The aim of this study is to investigate the value of the mPAP/CO slope in patients with more than moderate primary mitral regurgitation (MR) with preserved ejection fraction and no or discordant symptoms. A total of 128 consecutive patients were evaluated with exercise echocardiography and cardiopulmonary testing. Clinical outcome was defined as the composite of mitral valve intervention, new-onset atrial fibrillation, cardiovascular hospitalization, and all-cause mortality. The mean age was 63 years, 61% were male, and the mean LVEF was 66 ± 6%. The mPAP/CO slope correlated with peak VO2 (r = -0.52, P < 0.001), while the peak systolic pulmonary artery pressure (sPAP) did not (r = -0.06, P = 0.584). Forty-six per cent (n = 59) had peak exercise sPAP ≥60 mmHg, and 37% (n = 47) had mPAP/CO slope >3 mmHg/L/min. Event-free survival was 55% at 1 year and 46% at 2 years, with reduced survival in patients with mPAP/CO slope >3 mmHg/L/min (hazard ratio, 4.9; 95% confidence interval, 2.9-8.2; P < 0.001). In 53 cases (41%), mPAP/CO slope and peak sPAP were discordant: patients with slope >3 mmHg/L/mmHg and sPAP <60 mmHg (n = 21) had worse outcome vs. peak sPAP ≥60 mmHg and normal slope (n = 32, log-rank P = 0.003). The mPAP/CO slope improved predictive models for outcome, incremental to resting and exercise sPAP, and peak VO2. Exercise PH defined by the mPAP/CO slope >3 mmHg/L/min is associated with decreased exercise capacity and a higher risk of adverse events in significant primary MR and no or discordant symptoms. The slope provides a greater prognostic value than single sPAP measures and peak VO2.

Usefulness of cardiopulmonary exercise test to detect exercise pulmonary hypertension in the post pulmonary embolim follow-up

Abstract Functional impairment is largely reported after symptomatic pulmonary embolism (PE). Chronic thromboembolic pulmonary disease (CTED) refers to the presence of chronic thrombotic pulmonary vascular occlusion in the absence of pulmonary hypertension (PH) at rest but with incipient vasculopathy responsible for exercise limitation. Exercise haemodynamic studies have emerged to detect an abnormal response suggesting an established vasculopathy or an abnormal left ventricular filling pressure. We hypothesized that exercise intolerance due to an abnormal haemodynamic response during exercise might be unmasked by the parameters exhibited at the cardiopulmonary exercise test (CPET) in diagnostic workup after PE in symptomatic patients. Our aim was to correlate the values reached in the CPET pattern with haemodynamic response during exercise right heart catheterization (RHC) in patients with CTED suspicion. Methods We selected symptomatic patients with confirmed perfusion defects in lung scintigraphy despite optimal anticoagulant therapy for a minimum of 3 months after a PE with normal lung function tests. Left heart disease and significant PH were ruled out with RHC (inclusion criteria implied mean pulmonary arterial pressure (mPAP) &amp;lt; 25 mmHg and pulmonary vascular resistance (PVR) &amp;lt; 3 WU and pulmonary arterial wedge pressure (PAWP) ≤15 mmHg). Exercise RHC was performed sequentially 24 hours after CPET. The exercise protocol was the same for both tests. Pulmonary pressure and cardiac output (CO) were collected at each exercise leel. Exercise PH (ex-PH) was considered when mPAP/CO slope &amp;gt;3 mmHg·L−1·min−1. We made a subanalysis according to the new PH criteria (mPAP &amp;gt;20mmHg &amp; PVR &amp;gt; 2 WU at rest). Results 39 patients (median age 52.7 ± 15.7 years, 36% females) were included. 21 (53.8%) showed abnormal haemodynamic behaviour, 6(15.4%) of them due to abnormal PWAP/CO slope. Baseline characteristics are summarized in Table 1. Patients with abnormal exercise response showed worse ventilatory efficiency at exercise: 1) reduced partial end-tidal of carbon dioxide (PetCO2) at the anaerobic threshold (AT) (32.0 Vs 36.4, p=0.001), 2) a steeper VE/CO2 slope (35.6 Vs 30.9, p=0.009) and 3) a higher ventilatory equivalent for CO2 at the AT (35.5 Vs 31.6, p=0.004) compared to the group with normal hemodynamic behaviour. Oxygen consumption at the AT and peak oxygen consumption were slightly decreased without statistically significant differences between groups.Of the global cohort, 11 patients reached new resting PH criteria, and 92% of them showed ex-PH. Ventilatory efficiency showed differences in the subgroup with normal resting hemodynamic values, especially lower PetCO2 at the AT (31.8 Vs 35.0, p=0.008) (Figure 2). Conclusion In the context of persistent dyspnoea after PE, ventilatory inefficiency is a sign of exercise pulmonary hypertension, and CPET could identify patients with abnormal exercise response despite normal hemodynamic values at rest.

A comparative study on the diagnostic efficacy of different diagnostic criteria for exercise pulmonary hypertension

BackgroundExercise pulmonary hypertension (ePH) has three common diagnostic criteria: the mean pulmonary artery pressure (mPAP) > 30 mmHg and total pulmonary resistance (TPR) at peak exercise >3 Wood units (“Joint criteria”), the mPAP/cardiac output (CO) slope of the two-point measurement (ΔmPAP/ΔCO) > 3 mmHg/L/min (“Two-point criteria”), and the mPAP/CO slope of the multi-point data >3 mmHg/L/min (“Multi-point criteria”). We compared the diagnostic efficacy of these criteria, which remain controversial. MethodsFollowing resting right heart catheterization (RHC), all patients underwent exercise RHC (eRHC). The patients were divided into different ePH and non-exercise pulmonary hypertension (nPH) groups according to the above criteria. Joint criteria were used as the reference to compare the other two, namely diagnostic concordance, sensitivity and specificity. We conducted further analysis to determine the correlation between different diagnostic criteria grouping and the clinical severity of PH. ResultsThirty-three patients with mPAPrest ≤ 20 mmHg were enrolled. a) Diagnostic concordance, sensitivity and specificity: compared with Joint criteria, the diagnostic concordances of Two-point criteria and Multi-point criteria were 78.8% (κ = 0.570, P < 0.01) and 90.9% (κ = 0.818, P < 0.01), respectively; the sensitivity of Two-point criteria was high (100%), but the specificity was poor (56.3%); however, Multi-point criteria exhibited higher sensitivity (94.1%) and specificity (87.5%). b) Clinically relevant analysis: a significant difference was observed in several clinical severity indicators between ePH and nPH patients according to Multi-point criteria grouping(all P < 0.05). ConclusionMulti-point criteria are more clinically relevant and provide better diagnostic efficiency.

Heart failure with preserved ejection fraction: relevance of a dedicated dyspnoea clinic

Heart failure with preserved ejection fraction (HFpEF) is a syndrome with a heterogeneous presentation. This study provides an in-;depth description of haemodynamic and metabolic alterations revealed by systematic assessment through cardiopulmonary exercise testing combined with exercise echocardiography (CPETecho) within a dedicated dyspnoea clinic. Consecutive patients (n = 297), referred to a dedicated dyspnoea clinic using a standardized workup including CPETecho, with HFpEF diagnosed through a H2FPEF score ≥6 or HFA-PEFF score ≥5, were evaluated. A median of four haemodynamic/metabolic alterations was uncovered per patient: impaired stroke volume reserve (73%), impaired chronotropic reserve (72%), exercise pulmonary hypertension (65%), and impaired diastolic reserve (64%) were the most frequent cardiac alterations. Impaired peripheral oxygen extraction and a ventilatory limitation were present in 40% and 39%, respectively. In 267 patients (90%), 575 further diagnostic examinations were recommended (median of two tests per patient). Cardiac magnetic resonance imaging, coronary or amyloidosis workup, ventilation-perfusion scanning, and pulmonology referral were each recommended in approximately one out of three patients. In 293 patients (99%), 929 cardiovascular drug optimizations were performed (median of 3 modifications per patient). In 110 patients (37%), 132 cardiovascular interventions were performed, with ablation as the most frequent procedure. Holistic workup of HFpEF patients within a multidisciplinary, dedicated dyspnoea clinic, including systematic implementation of CPETecho reveals various haemodynamic/metabolic alterations, leading to further diagnostic testing and potential treatment changes in the majority of cases.

Isolated unilateral absence of pulmonary artery- an unusual cause of hemoptysis: a case report

BackgroundIsolated unilateral absence of one pulmonary artery (IUAPA) is a rare malformation and a rare cause of hemoptysis. It occurs due to malformation of the sixth aortic arch during embryogenesis. This condition has variable presentations like dyspnoea, reduced exercise tolerance, chest pain, pleural effusion, recurrent bronchopneumonia, pulmonary hypertension, and haemoptysis can be asymptomatic.Case PresentationWe describe a case of a 34-year-old female presenting with recent onset hemoptysis associated with mild dyspnoea and cough. Chest Radiograph revealed unilateral hyperlucent lung field which was later diagnosed as Isolated unilateral absence of pulmonary artery on high resolution computed tomography of chest with angiography.ConclusionAbsent pulmonary artery should be considered as an important differential in cases presenting with hemoptysis. This case emphasises the significance of combining computed tomography with pulmonary angiography to accurately evaluate and define congenital lung abnormalities.

How do we respond to the newly-revised haemodynamic definitions of pulmonary hypertension

In August 2022, the European Society of Cardiology (ESC) and the European Respiratory Society (ERS) jointly issued the 2022 ESC/ERS Guidelines for the Diagnosis and Treatment of Pulmonary Hypertension, which updated the hemodynamic diagnostic criteria for pulmonary hypertension, causing widespread debate among experts. How should we respond to the updated diagnostic criteria for pulmonary hypertension? This paper analyzes the origin of the diagnostic criteria for pulmonary hypertension, how to understand the newly revised diagnostic criteria for hemodynamics, the definition of the new criteria for exercise pulmonary hypertension, and the important impact of the new diagnostic criteria on clinical practice, and puts forward countermeasures.

Updated definition of exercise pulmonary hypertension.

In the recently published European Society of Cardiology/European Respiratory Society guidelines on the diagnosis and treatment of pulmonary hypertension (PH) the haemodynamic definitions of PH were updated and a new definition for exercise PH was introduced. Accordingly, exercise PH is characterised by a mean pulmonary arterial pressure/cardiac output (CO) slope >3 Wood units (WU) from rest to exercise. This threshold is supported by several studies demonstrating prognostic and diagnostic relevance of exercise haemodynamics in various patient cohorts. From a differential diagnostic point of view, an elevated pulmonary arterial wedge pressure/CO slope >2 WU may be suitable to identify post-capillary causes of exercise PH. Right heart catheterisation remains the gold standard to assess pulmonary haemodynamics both at rest and exercise. In this review, we discuss the evidence that led to the reintroduction of exercise PH in the PH definitions.

Prevalence and implications of exercise pulmonary hypertension in chronic thromboembolic pulmonary disease

Abstract Introduction Recent international statement on chronic thromboembolic pulmonary hypertension proposed the definition of chronic thromboembolic pulmonary disease (CTEPD) and advocated further research regarding its clinical characteristic, natural history, and therapeutic strategy. Exercise pulmonary hypertension (Ex-PH) has been considered a mild degree of pulmonary hypertension (PH) among patients with normal pulmonary hemodynamics at rest. However, the clinical significance of Ex-PH in CTEPD remains unknown. Purpose In the patients with CTEPD, we aimed to verify 1) the prevalence and clinical profiles of Ex-PH, 2) effect of BPA on pulmonary vascular response after exercise in Ex-PH, 3) long-term clinical outcomes of conservative management in non-Ex-PH. Methods We retrospectively reviewed 26 patients with CTEPD (median age 65 years, 38% male), who underwent cardiopulmonary exercise test with right heart catheterization (CPET-RHC). The definitions of CTEPD are the following 1) pulmonary artery occlusion due to organic thrombus confirmed by imaging studies after ≥3 months of anticoagulation, 2) mPAP&amp;lt;25 mmHg and PAWP≤15 mmHg at rest. PQslope was plotted using multipoint plots. Ex-PH was defined by PQ slope&amp;gt;3.0, and the patients were divided into Ex-PH and non-Ex PH groups. Clinical profiles and long-term outcomes were compared between two groups. The patients in Ex-PH groupunderwent CPET-RHC 6–12 months after balloon pulmonary angioplasty (BPA). In Non-Ex-PH group, serial measurements of echocardiography were performed. Results Overall, 5 and 21 patients were categorized as CTEPD with PH (mPAP 21–24mmHg) and without PH (mPAP≤20mmHg), and 14 and 12 were categorized Ex-PH and non-Ex-PH groups, respectively. Although all 5 patients with CTEPD with PH were classified as Ex-PH group (Figure 1), there was no significant difference in baseline hemodynamics at rest between Ex-PH and non-Ex-PH groups (mPAP: 19.5 [18.4–20.6] vs. 17.7 [16.6–18.9] mmHg, PVR: 2.2 [1.7–2.7] vs. 2.3 [1.9–2.8] wood units, P&amp;gt;0.05, respectively). PQ slope was significantly higher in Ex-PH group (4.6 [3.2–6.0] vs. 1.31 [0.2–2.8], p=0.002). There were no differences in respiratory function test, blood gas analysis, and 6-minute walk distance between two groups. There were no major adverse events such as all-cause mortality and hospitalization for PH in overall cohort. Among Ex-PH group, BPA decreased PQslope (4.8 [3.6–6.4] to 2.3 [1.9–3.0], p&amp;lt;0.05). Among no-Ex-PH group, there was no significant change in tricuspid regurgitation pressure gradient (28 [17–33] to 27 [21–36] mmHg, p&amp;gt;0.05) over the 997 [651–1451] days. Conclusion Ex-PH was common in patients with CTEPD, and there were no clinical profiles differentiating Ex-PH from non-Ex-PH, except parameters of CPET-RHC. BPA improved an abnormal pulmonary vascular response to exercise in Ex-PH. The conservative management in non-Ex-PH was feasible. Randomized clinical trials will be needed to further investigate this treatment strategy. Funding Acknowledgement Type of funding sources: None.

Role of combined exercise stress echocardiography and cardiopulmonary exercise test in chronic thromboembolic disease

Abstract Background Chronic thromboembolic pulmonary disease (CTEPD) without pulmonary hypertension could cause significant exercise limitations. However, interventional or surgical treatments for CTEPD with mild pulmonary hypertension or normal pressure are on controversy. Purpose We aimed to evaluate cardiopulmonary function through cardiopulmonary exercise test (CPET) with stress echocardiography and to determine whether exercise pulmonary hypertension can explain exercise limitations in CTEPD patients with mPAP &amp;lt;30mmHg. Methods Patients diagnosed as CTEPD with mPAP less than 30mmHg was derived from our pulmonary hypertension center registry from April 2014 to October 2021.Transthoracic echocardiography (TTE) was performed at baseline (resting state) and immediately after CPET. TTE derived parameters and CPET parameters were compared with hemodynamic parameters measured by right catheterization. Results Total 37 patients were enrolled. Of these, Thirty-five patients had previously been diagnosed with CTEPH and had undergone PEA, BPA, or both. Most of the patients complained dyspnea of WHO functional class II or III. Pulmonary vascular resistance (PVR) was slightly higher than normal (185.0±102.2 dyne sec cm–5). Also VO2max was decreased in CPET (23.1±6.5 mL/kg/min). In correlation analysis, the higher the mPAP and PVR at rest, the lower VO2max during exercise. Meanwhile basal right ventricular (RV) function was normal, an increase in RVSP was notably observed during exercise (RVSP: pre-exercise 36.2±11.9, post-exercise 60.7±19.3, p value &amp;lt;0.001). Furthermore RV function deteriorated during exercise (TAPSE: pre-exercise 16.1±4.8, post-exercise 12.9±5.0, p value &amp;lt;0.001). Conclusions CTEPD patients with mild or normal PAP showed limited exercise capacity with exercise induced hypertension. Even in the mPAP less than 30mmHg, PVR and mPAP was significantly associated with exercise capacity. CPET with stress echocardiography could help to identify the main cause of exercise limitation in CTEPD patients and possibly provide the guideline for treatment plan. Funding Acknowledgement Type of funding sources: None.

Different diagnostic criteria agreement for exercise pulmonary hypertension in chronic thromboembolic pulmonary disease

Abstract Background Hemodynamic changes during exercise have emerged as a diagnostic tool in patients with suspected pulmonary hypertension, considering that an abnormal response may reveal an incipient vasculopathy, particularly in chronic thromboembolic disease (CTED). Since mean arterial pressure (mPAP) is considered a flow-dependent variable, diagnosis of an abnormal pulmonary hemodynamic response has changed over time. Different methods to determine a pathological mPAP to Cardiac Output (CO) ratio have been proposed. Multipoint mPAP – CO Slope &amp;gt;3 mmHg/L/min has reached board consensus for determining an abnormal pulmonary response to exercise as this method can characterize mPAP–CO response across all exercise stages. Given the technic difficulties to obtain this parameter, other criteria have been proposed. Aim To investigate the diagnostic concordance and the reproducibility of the different abnormal pulmonary exercise hemodynamic response criteria in a cohort of patients with CTED. Methods We selected symptomatic patients with confirmed perfusion defects in lung scintigraphy despite optimal anticoagulant therapy for a minimum of 6 months after a pulmonary embolism. The thrombotic burden was assessed with computed tomography (CT). Lelf Heart Disease (LHD) and significant PH were ruled out with RHC (inclusion criteria implied resting mean pulmonary arterial pressure (mPAP) &amp;lt;25 mmHg and pulmonary vascular resistance (PVR) &amp;lt;3 uW and pulmonary arterial wedge pressure (PAWP) &amp;lt;15 mmHg). Exercise RHC was performed in supine position following an incremental stepwise protocol using a cycle ergometer. Pulmonary pressures and CO estimated by thermodilution were collected at each exercise level. Total pulmonary resistance (TPR) was calculated by dividing mPAP by CO. The abnormal hemodynamic response according to the more viable proposed criteria: 1) mPAP &amp;gt;30 mmHg and TPR &amp;gt;3uW at peak exercise, 2) ΔmPAP/ ΔCO &amp;gt;3 mmHg/L/min at rest and peak exercise; was compared to the pathological reference threshold multipoint PAPm/ CO slope &amp;gt;3 mmHg/L/min. Results 22 patients (median age of 54.5±14.8 years old) were recruited. Baseline characteristics and RHC values are summarized in Figure 1. Positive agreement was 93% (77% – 98%) in case of mPAP30peak+ TPR3peak versus mPAP/CO slope (k=0.810) and 91% (74% – 97%) in case of ΔmPAP/ΔCO versus mPAP/CO slope (k=0.801). Both criteria showed high diagnostic accuracy for an abnormal response diagnosis compared with the reference. Figure 2 summarizes their respective sensitivities and specificities. Patients misdiagnosed were those whose hemodynamic response was close to the reference cut-off values (mPAP/CO slope between 2 and 4 mmHg//L/min). Conclusion In a cohort of patients with CTED without significant PH at rest or LHD,the three methods proposed to diagnose an abnormal pulmonary exercise hemodynamic response show accurate concordance. Disagreement was higher in patients with a borderline pathological response. Funding Acknowledgement Type of funding sources: Public Institution(s). Main funding source(s): Sociedad Española de Cardiologia

Exercise Pulmonary Hypertension

Exercise Pulmonary Hypertension

Phenotyping exercise limitation of patients with Interstitial Fibrosing Lung Disease: the importance of exercise hemodynamics

Introduction and objectiveLeft-heart dysfunction and pulmonary vasculopathy are increasingly recognized as contributing factors of exercise capacity limitation in interstitial fibrosing lung disease (IFLD). Moreover, the clinical significance of exercise pulmonary hypertension (ePH) in pulmonary and cardiac diseases has been documented, representing a risk factor for decreased exercise capacity and survival, progression to resting pulmonary hypertension (PH) and overall clinical worsening.We conducted a prospective study aiming at: (a) assessing the prevalence of PH and ePH in a cohort of 40 functionally limited patients with IFLD, (b) determining the post-capillary (postC) or pre-capillary (preC) etiology of either PH or ePH in this cohort, and (c) examining the correlations between invasively and non-invasively measured exercise variables among hemodynamic groups. Patients and methods40 IFLD patients underwent cardiopulmonary evaluation, including: clinical examination, lung function tests, 6-minute walking test, heart ultrasonography, cardiopulmonary exercise test and, finally, right heart catheterization (RHC). Resting hemodynamic evaluation was followed by the exercise protocol proposed by Herve et al, using a bedside cycle ergometer in the supine position. Abnormal elevation of mean pulmonary artery pressure (mPAP) above 30mmHg during exercise, with respect to abnormal elevation of cardiac output (CO) below 10 L/min (mPAP–CO ratio ⩾3 mmHg·min·L−1) was used to define ePH (Herve et al, 2015). Secondary hemodynamic evaluation involved detection of abnormal pulmonary arterial wedge pressure (PAWP) increase at peak exercise in relation to CO. Specifically, ΔPAWP/ΔCO >2 mmHg/L per minute determined an abnormal PAWP elevation (Bentley et al, 2020). ResultsAmong the 40-patient cohort, 25% presented postC PH, 37.5% preC PH, 27.5% ePH, with the remaining 10% recording normal hemodynamics. PAWP evaluation during exercise revealed a postC etiology in 4 out of the 11 patients presenting ePH, and a postC etiology in 6 out of the 15 patients presenting resting preC PH. Mean values of non-invasive variables did not display statistically significant differences among hemodynamic groups, except for: diffusing capacity for carbon monoxide (DLCO), carbon monoxide transfer coefficient (KCO) and the ratio of functional vital capacity to DLCO (FVC%/DLCO%), which were lower in both ePH and PH groups (p < 0.05). Resting values of CO, cardiac index (CI), stroke volume (SV) and pulmonary vascular compliance (PVC) were significantly impaired in ePH, preC-PH and postC-PH groups when compared to the normal group. ConclusionsBoth PH and ePH were highly prevalent within the IFLD patient group, suggesting that RHC should be offered more frequently in functionally limited patients. Diffusion capacity markers must thus guide decision making, in parallel to clinical evaluation. ePH was associated to lower resting CO and PVC, in a similar way to resting PH, indicating the relevance of cardiopulmonary function to exercise limitation. Finally, the use of the ΔPAWP/ΔCO>2 criterion further uncovered PH of postcapillary etiology, highlighting the complexity of hemodynamics in IFLD.ClinicalTrials.gov ID: NCT03706820

Exercise Systolic Reserve and Exercise Pulmonary Hypertension Improve Diagnosis of Heart Failure With Preserved Ejection Fraction.

AimsDiastolic stress testing (DST) is recommended to confirm heart failure with preserved ejection fraction (HFpEF) in patients with exertional dyspnea, but current algorithms do not detect all patients. We aimed to identify additional echocardiographic markers of elevated pulmonary arterial wedge pressure during exercise (exPAWP) in patients referred for DST.Methods and ResultsWe identified candidate parameters in 22 patients referred for exercise right heart catheterization with simultaneous echocardiography. Elevated exPAWP (≥25 mmHg) was present in 14 patients, and was best identified by peak septal systolic annular velocity <9.5 cm/s [exS', area under the receiver operating characteristic curve (AUC) 0.97, 95% confidence interval 0.92–1.0] and mean pulmonary artery pressure/cardiac output slope ≥3.2 mmHg/L [mPAP/CO, AUC 0.88 (0.72–1.0)]. We propose a decision tree to identify patients with elevated exPAWP. Applying this decision tree to 326 patients in an independent non-invasive DST cohort showed that patients labeled as “high probability of HFpEF” (n = 85) had reduced peak oxygen uptake [13.0 (10.7–15.1) mL/kg/min, p < 0.001 vs. intermediate/low probability], high H2FPEF score [53 (40–72) %, p < 0.001 vs. intermediate/low probability], and typical clinical characteristics. The diagnostic yield of DST increased from 11% using exercise E/e', to 62% using the decision tree.ConclusionIn DST for suspected HFpEF, exS' was the most accurate echocardiographic parameter to identify elevated PAWP. We propose a decision tree including exS' and mPAP/CO for interpretation of DST. Application of this decision tree revealed typical HFpEF characteristics in patients labeled as high probability of HFpEF, and substantially reduced the number of inconclusive results.

Successful epoprostenol withdrawal and termination with an aid of the exercise stress test in pulmonary arterial hypertension

Continuous infusion of intravenous epoprostenol (EPO) improves exercise capacity and survival in pulmonary arterial hypertension (PAH); however, it is associated with side effects. This study aimed to describe our experience on safe EPO withdrawal with the aid of an exercise stress test.This retrospective review included patients with PAH who were successfully withdrawn from EPO. Haemodynamic data were obtained before EPO administration, at withdrawal, and after discontinuation. After the mean pulmonary arterial pressure (mPAP) decreased to <25 mmHg for at least 1 year, an exercise test under right heart catheterisation was performed. If exercise pulmonary hypertension was not record (mPAP - cardiac output slope < 3), EPO was withdrawn.Of the 99 patients who received EPO, ten were identified as having undergone withdrawal or termination. mPAP decreased from 61 (54–71) mmHg before treatment to 19 (17–21) mmHg before withdrawal and remained unchanged, at 19 (14–23) mmHg, 1 year after EPO discontinuation. After a median follow-up of 32 months, all the patients survived.Patients with PAH who recovered their normal haemodynamic function were safely withdrawn from EPO with the aid of an exercise stress test.

Abstract 13282: Oxygen Uptake and Cardiac Output Exhibit Delayed Recovery After Maximum Incremental Ramp Exercise in Patients With Exercise Pulmonary Hypertension

Introduction: In individuals with dyspnea on exertion (DOE) and suspected exercise pulmonary hypertension (exPH), oxygen uptake (VO 2 ), cardiac output (CO), peripheral oxygen extraction (Ca-vO 2 ), and mean pulmonary artery pressure (mPAP) have been well characterized during incremental exercise but less is known about the kinetics of post-exercise recovery patterns. Hypothesis: Exercise recovery cardiac output kinetics are slowed in patients with exPH. Methods: Upright maximum incremental ramp cycle ergometry cardiopulmonary exercise testing with invasive hemodynamic monitoring and serial blood gas measurements during exercise and recovery was performed in 50 consecutive patients referred for evaluation of DOE of unclear etiology. VO 2 , arterial and venous oxygen content (Ca-vO 2 ), Fick cardiac output, and mPAP were analyzed from rest, peak exercise, and 2 minutes post-exercise. ExPH was defined in a consistent manner with recent consensus statements (ΔmPAP/ΔCO &gt;3.0 mmHg/L/min) from rest to peak exercise. Results: Among 50 patients with DOE, [62% female, Age 61.7±11.8, BMI 30.7±8.2] 2-min post-exercise VO 2 was -56±11%, CO: -22±19%, Ca-vO 2 :-42±15% compared to peak exercise values. The % fall in CO at 2min was significantly lower in the 26 patients with exPH compared to the 24 patients without exPH (Table). The average mPAP remained elevated at 2 min post-exercise (&gt;20mmHg) in exPH despite normal average resting values. Conclusions: Patients with exPH demonstrate slowed CO recovery kinetics in conjunction with persistent PAP elevation 2-min post-exercise. Persistent elevation in blood flow through the pulmonary circuit at a time conducive to non-invasive assessment of PAP (i.e. by echocardiography) may lend itself to non-invasive detection of exercise-PH in patients undergoing evaluation of dyspnea on exertion.

Prognostic values of exercise echocardiography and cardiopulmonary exercise testing in patients with primary mitral regurgitation

To compare the clinical significance of exercise echocardiography (ExE) and cardiopulmonary exercise testing (CPX) in patients with ≥moderate primary mitral regurgitation (MR) and discrepancy between symptoms and MR severity. Patients consulting for ≥moderate discordant primary MR prospectively underwent low (25 W) ExE, peak ExE, and CPX within 2 months in Lille and Rennes University Hospital. Patients with Class I recommendation for surgical MR correction were excluded. Changes in MR severity, systolic pulmonary artery pressure (SPAP), left ventricular ejection fraction (LVEF), and tricuspid annular plane systolic excursion were evaluated during ExE. Patients were followed for major events (ME): cardiovascular death, acute heart failure, or mitral valve surgery. Among 128 patients included, 22 presented mild-to-moderate, 61 moderate-to-severe, and 45 severe MR. Unlike MR variation, SPAP and LVEF were successfully assessed during ExE in most patients. Forty-one patients (32%) displayed reduced aerobic capacity (peak VO2 &lt; 80% of predicted value) with cardiac limitation in 28 (68%) and muscular or respiratory limitation in the 13 others (32%). ME occurred in 61 patients (47.7%) during a mean follow-up of 27 ± 21 months. Twenty-five Watts SPAP [hazard ratio (HR) (95% confidence interval, CI) = 1.03 (1.01-1.06), P = 0.003] and reduced aerobic capacity [HR (95% CI) = 1.74 (1.03-2.95), P = 0.04] were independently predictive of ME, even after adjustment for MR severity. The cut-off of 55 mmHg for 25 W SPAP showed the best accuracy to predict ME (area under the curve = 0.60, P = 0.05). In patients with ≥moderate primary MR and discordant symptoms, 25 W exercise pulmonary hypertension, defined as an SPAP ≥55 mmHg, and poor aerobic capacity during CPX are independently associated with adverse events.

P16‐110: THE co‐relation between exercise capacity and pulmonary hypertension in different types of interstitial lung diseases in a Tertiary Care Center in India

P16‐110: THE co‐relation between exercise capacity and pulmonary hypertension in different types of interstitial lung diseases in a Tertiary Care Center in India

Quantification of Arterial and Venous Morphologic Markers in Pulmonary Arterial Hypertension Using CT Imaging

BackgroundPulmonary hypertension is a heterogeneous disease, and a significant portion of patients at risk for it have CT imaging available. Advanced automated processing techniques could be leveraged for early detection, screening, and development of quantitative phenotypes. Pruning and vascular tortuosity have been previously described in pulmonary arterial hypertension (PAH), but the extent of these phenomena in arterial vs venous pulmonary vasculature and in exercise pulmonary hypertension (ePH) have not been described.Research QuestionWhat are the arterial and venous manifestations of pruning and vascular tortuosity using CT imaging in PAH, and do they also occur in ePH?Study Design and MethodsA cohort of patients with PAH and ePH and control subjects with available CT angiograms were retrospectively identified to examine the differential arterial and venous presence of pruning and tortuosity in patients with precapillary pulmonary hypertension not confounded by lung or thromboembolic disease. The pulmonary vasculature was reconstructed, and an artificial intelligence method was used to separate arteries and veins and to compute arterial and venous vascular volumes and tortuosity.ResultsA total of 42 patients with PAH, 12 patients with ePH, and 37 control subjects were identified. There was relatively lower (median [interquartile range]) arterial small vessel volume in subjects with PAH (PAH 14.7 [11.7-16.5; P < .0001]) vs control subjects (16.9 [15.6-19.2]) and venous small vessel volume in subjects with PAH and ePH (PAH 8.0 [6.5-9.6; P < .0001]; ePH, 7.8 [7.5-11.4; P = .004]) vs control subjects (11.5 [10.6-12.2]). Higher large arterial volume, however, was only observed in the pulmonary arteries (PAH 17.1 [13.6-23.4; P < .0001] vs control subjects 11.4 [8.1-15.4]). Similarly, tortuosity was higher in the pulmonary arteries in the PAH group (PAH 3.5 [3.3-3.6; P = .0002] vs control 3.2 [3.2-3.3]).InterpretationLower small distal pulmonary vascular volume, higher proximal arterial volume, and higher arterial tortuosity were observed in PAH. These can be quantified by using automated techniques from clinically acquired CT scans of patients with ePH and resting PAH.