Exercise-induced Pulmonary Hypertension Research Articles

Use of thermodilution cardiac output overestimates diagnoses of exercise-induced pulmonary hypertension.

Two new definitions of exercise-induced pulmonary hypertension (EIPH) have emerged. Both rely on measuring cardiac output (CO), yet this remains unstandardized. In our cohort of patients undergoing invasive cardiopulmonary exercise testing, we found that using thermodilution CO rather than direct Fick CO led to a significant excess of EIPH diagnoses.

A Case of Exercise-Induced Chest Pain Due to Anomalous Right Coronary Artery

A 58-year-old male presented with 6-month history of exertional chest pain on a background of family history of family history of sudden death in brother at the age of 50. He underwent coronary angiogram and subsequent CTCA after positive exercise stress test. There was anomalous anterior origin of right coronary artery arising from left coronary cusp, coursing between the pulmonary artery and aorta without significant coronary stenosis. (Fig. 1). Heart team meeting consensus was that chest pain was due to exercise-induced pulmonary hypertension and patient was offered single coronary artery bypass grafting. Patient is doing well without recurrence of pain at 3 months of follow-up. The clinical outcome for ARCA is most often benign. Exercise induced cyclical compression and distorted slit-like ostium are thought to be mechanism of ischaemia. Patients who have symptoms of ischaemia or arrhythmia warrant more urgent surgical intervention, both for management of symptoms and reduction in risk of sudden cardiac death [[1]Ghosh P.K. Agarwal S.K. Kumar R. Chandra N. Puri V.K. Anomalous origin of right coronary artery from left aortic sinus.J Cardiovasc Surg (Torino). 1994; 35: 65-70PubMed Google Scholar]. This case illustrates the importance of considering ARCA as a differential diagnosis in patients presenting with exercise induced ischaemic chest pain, without any alternative explanations.

When exploring patients during exercise makes sense?

This editorial refers to ‘Clinical characteristics and determinants of exercise-induced pulmonary hypertension in patients with preserved left ventricular ejection fraction’, by A. Young Lim et al. doi: 10.1093/ehjci/jew199. Dealing with exertional dyspnoea or unexplained shortness of breath is a common problem in clinical practice. However, the exploration of such symptoms is difficult and does not always lead to definite positive diagnosis and thus appropriate treatment. Moreover, the perception of dyspnoea is subjective and relies on determinants that are often unclear. In these patients, exploring pulmonary pressures and diastolic function during exercise appears to be an interesting way to assess the potential causes triggering their symptoms. In this issue of European Heart Journal - Cardiovascular Imaging , Lim et al. 1 present a remarkable study exploring the value of exercise-induced pulmonary hypertension (EIPH) in patients with preserved left ventricular ejection fraction and complaining about unexplained dyspnoea. This exhaustive work included a large number of patients (1383 were analysed) and enabled a comprehensive description of the clinical aspects and features of EIPH in this population. To date, this population has not been well characterized, so the data published in this issue allow interesting insights in this not-so-well-known clinical entity. EIPH has been explored and demonstrated as clinically interesting in the field of heart valve diseases and in the prognostic assessment of patients diagnosed for a heart failure with preserved ejection fraction.2–4 Notably, larger studies confirming those first results are mandatory to justify a more generalized use of exercise stress echocardiography in our routine clinical practice. The first surprising fact in the study by Lim et al . appears to be the population with …

Left ventricular deformation at rest predicts exercise-induced elevation in pulmonary artery wedge pressure in patients with unexplained dyspnoea.

Impaired left ventricular (LV) deformation despite preserved LV ejection fraction (LVEF) is common and predicts outcomes in heart failure with preserved LVEF. We hypothesized that impaired LV deformation at rest is a marker of impaired cardiac systolic and diastolic reserve, and aimed to determine whether resting longitudinal (LS) and circumferential strain (CS) are associated with invasively measured haemodynamic response to exercise in patients with dyspnoea and a normal LVEF. We studied 85 patients with LVEF ≥50% and free of significant valvular disease who were referred for evaluation of dyspnoea. All patients underwent rest echocardiography followed by right heart catheterization and cardiopulmonary exercise testing with concomitant invasive haemodynamic monitoring. The LS, CS and CS/LS ratio were measured by two-dimensional speckle-tracking echocardiography at rest. Lower absolute LS at rest was associated with greater increase in pulmonary arterial wedge pressure (PAWP) from rest to peak exercise (r = 0.23, P = 0.034). In contrast, higher absolute CS at rest predicted a greater increase in PAWP (r = - 0.27, P = 0.032) and greater stroke volume augmentation with exercise (r = - 0.26, P = 0.021). Higher CS/LS ratio was most predictive of elevation in PAWP with exercise (r = 0.30, P = 0.015). Of the measures of LV systolic and diastolic function assessed, the CS/LS ratio resulted in the highest area under the curve and specificity for the presence of rest- or exercise-induced pulmonary venous hypertension. Left ventricular deformation at rest predicts exercise-induced rise in PAWP among patients with dyspnoea and a preserved LVEF. A pattern of rest deformation characterized by worse LS and exaggerated CS is most strongly associated with exercise-induced rise in PAWP.

Exercise-induced pulmonary hypertension by stress echocardiography: Prevalence and correlation with right heart hemodynamics

ObjectivesThe aim of this study was to determine the prevalence of exercise-induced pulmonary hypertension (EIPH) in consecutive subjects referred for stress echocardiography for chest pain or shortness of breath and correlate echocardiographic diagnosis of EIPH with hemodynamics at right heart catheterization (RHC). BackgroundElevated pulmonary pressure can lead to significant morbidity and mortality. EIPH by ehocardiography has been described in patients with connective tissue disease. It's prevalence in the setting of routine clinically indicated stress echocardiography unknown. MethodsIn a retrospective analysis of 4068 consecutive stress subjects undergoing stress echocardiography, 479 subjects with EIPH were identified. All 479 subjects with EIPH were compared to 479 age and sex matched subjects with normal pulmonary artery pressures post exercise. EIPH was defined as PASP>50mmHg or peak tricuspid regurgitation velocity>3.2m/s. Of 100 patients with EIPH who underwent RHC we identified variables which predicted abnormal hemodynamic findings on RHC. ResultsThe prevalence of EIPH in subjects referred for stress echocardiography was 11.7%. A greater proportion of subjects with EIPH were obese or had lung disease or connective tissue disease. Of 100 subjects who underwent RHC, 65 had abnormal results. Age>55years (OR 5.1, p<0.01]) or dilated left atrium (OR 4.4, p=0.02]) were independently associated with abnormal right heart hemodynamics. ConclusionsThe results demonstrate that 11.7% of patients undergoing clinically indicated stress echocardiography have EIPH. Of those who underwent RHC abnormal hemodynamics were significantly associated with a dilated left atrium or age older than 55years.

Ventricular-Arterial Coupling and Exercise-Induced Pulmonary Hypertension During Low-Level Exercise in Heart Failure With Preserved or Reduced Ejection Fraction

BackgroundExercise-induced pulmonary hypertension (EIPH) may develop even at low workloads in heart failure (HF) patients. Ventricular-arterial stiffening plays an important role in the pathophysiology of HF with preserved ejection fraction (HFpEF). This study aimed to compare the response of ventricular-arterial coupling and PH during low-level exercise between HFpEF and HF with reduced EF (HFrEF). Methods and ResultsEchocardiography was performed at rest and during 10 W of bicycle exercise in HFpEF (n = 37) and HFrEF (n = 43). Load-independent contractility (end-systolic elastance [Ees], preload recruitable stroke work [PRSW], and peak power index [PWRI]), arterial afterload (arterial elastance [Ea]), and ventricular-arterial interaction (Ea/Ees) were measured with the use of a noninvasive single-beat technique. EIPH was defined as an estimated pulmonary arterial systolic pressure (PASP) of ≥50 mm Hg at 10 W of exercise. PASP was significantly increased during 10 W of exercise in both HF types, and ~50% of HFpEF patients developed EIPH. Arterial afterload was increased significantly during exercise in both groups. HFrEF and HFpEF patients showed a significant increase in LV contractility assessed by Ees, PRSW, and PWRI during exercise. Although Ea/Ees ratio decreased significantly in HFrEF, reduction in Ea/Ees was attenuated because of blunted Ees increases in patients with HFpEF compared with HFrEF. ConclusionsEven at low-level exercise, ~50% of HFpEF patients developed EIPH. Reduction in Ea/Ees was attenuated owing to less Ees increase in HFpEF compared with HFrEF. Further studies are needed to elucidate the association between ventricular-arterial coupling and EIPH in HFpEF.

Exercise pulmonary haemodynamics predict outcome in patients with systemic sclerosis.

The aim of the present study was to investigate the prognostic value of exercise haemodynamics measured during right heart catheterisation (RHC) in patients with systemic sclerosis (SSc) referred for evaluation of pulmonary hypertension.SSc patients undergoing RHC at rest and during maximal supine incremental cycle exercise were grouped into resting precapillary pulmonary hypertension (PHrest) (mean pulmonary artery pressure (mPAP) ≥25 mmHg, pulmonary artery wedge pressure <15 mmHg), exercise-induced pulmonary hypertension (PHex) (mPAP ≥30 mmHg and mPAP/cardiac output >3 mmHg·L-1·min-1 at maximal exercise), and without pulmonary hypertension (PHnone). Patients' characteristics, haemodynamics and follow up data were compared between groups.72 SSc patients were followed for median (interquartile range) 33 (15-55) months. Mean (95% CI) survival without transplantation estimated by Kaplan-Meyer analysis was 4.4 (0.8-2.9) years in PHrest (n=17), 5.2 (4.4-6.1) years in PHex (n=28) and 9.5(8.4-10.6) years in PHnone (n=27; p<0.05 versus others). In Cox regression models, the exercise-induced increase in mPAP (hazard ratio (HR) 1.097, 95% CI 1.002-1.200) and the coefficient of pulmonary vascular distensibility alpha (HR 0.100, 95% CI 0.012-0.871) controlled for age, but not resting haemodynamics predicted transplant-free survival.Among SSc patients with normal mPAP at rest, an excessive increase in mPAP during exercise and an impaired vascular distensibility may indicate an early stage of pulmonary vasculopathy, associated with reduced survival similar to resting pulmonary hypertension patients.

PROGNOSTIC VALUE OF INCREASE IN SYSTOLIC PULMONARY ARTERIAL PRESSURE AT LOW LEVEL OF EXERCISE IN ASYMPTOMATIC PATIENTS WITH ORGANIC MITRAL REGURGITATION -RESULTS FROM THE PROGRAM STUDY

The optimal timing of mitral valve surgery in asymptomatic patients with chronic severe organic mitral regurgitation (MR) is controversial. Exercise-induced pulmonary arterial hypertension (systolic pulmonary arterial pressure [SPAP] > 60 mmHg) has been shown to predict cardiac events. The objective of this study was to examine the prognostic value of the increase in the SPAP during the early phase of the exercise test in asymptomatic organic MR.

A Case of Using Masitentan in Patient With Systemic Sclerosis (SSc) Diagnosised Exercise-Induced Pulmonary Hypertension Associated (PAH)

A Case of Using Masitentan in Patient With Systemic Sclerosis (SSc) Diagnosised Exercise-Induced Pulmonary Hypertension Associated (PAH)

The Evolving Landscape of Exercise-Induced Pulmonary Hypertension.

Normal pulmonary artery pressures at rest, with an exaggerated rise during exercise, characterize exercise-induced pulmonary hypertension. Exercise itself as it relates to this condition is not deleterious, nor does it cause or induce disease. However much like any classical stress test, it is a physiologic probe that aids in disease unmasking. Although more work is required to establish criteria for defining this clinical entity, the phenomenon is real. It remains unknown whether it represents a nascent form of cardiopulmonary disease and whether its genesis predicts fulminant cardiopulmonary disease. Incremental cardiopulmonary exercise testing and the construction of pressure-flow plots to describe the pulmonary vascular response to exercise will be essential in defining this disease. The critical first step remains a consensus definition that will allow for further prospective study focused by a common language.

Prediction of new onset of resting pulmonary arterial hypertension in systemic sclerosis

Early detection of pulmonary arterial hypertension (PH) is crucial in systemic scleroderma. However, predictors of new onset of resting PH during follow-up (FUPH) have been poorly explored. To determine whether nailfold videocapillaroscopy (NVC) grade and exercise echocardiographic variables are predictors of FUPH. We prospectively enrolled 40 patients with systemic sclerosis (age 54±13 years; 68% women). All patients underwent graded semisupine exercise echocardiography and NVC. Baseline resting PH and FUPH were defined as systolic pulmonary arterial pressure (sPAP)>35 mmHg, and exercise-induced PH (EIPH) as exercise sPAP>50 mmHg. Seventeen patients developed EIPH (43%). During follow-up (FU) (25±15 months), 11 patients without baseline PH developed FUPH (28%), all from the EIPH group. Patients with FUPH were significantly older (60±14 vs 50±12 years; P=0.04), had higher resting and exercise sPAP (30±4 vs 22±5 and 60±12 vs 40±11 mmHg, respectively; P<0.0001) and a higher exercise E/e' ratio (9.4±0.7 vs 5.8±0.4; P=0.0003) and presented more frequently NVC grade>2 (90% vs 35%; P=0.0009). After adjustment for age, resting sPAP, exercise sPAP and NVC grade>2 were associated with maximal resting sPAP during follow-up and FUPH (P<0.05). Patients with both EIPH and NVC grade>2 had a very high incidence of FUPH (82%), and both variables remained strongly associated with FUPH after adjustment for age (hazard ratio 11.6, 95% confidence interval 2.4-55.3; P=0.002). Exercise echocardiography and NVC can identify a subgroup of patients with systemic sclerosis who are at risk of developing FUPH.

Protocol for exercise hemodynamic assessment: performing an invasive cardiopulmonary exercise test in clinical practice.

Invasive cardiopulmonary exercise testing (iCPET) combines full central hemodynamic assessment with continuous measurements of pulmonary gas exchange and ventilation to help in understanding the pathophysiology underpinning unexplained exertional intolerance. There is increasing evidence to support the use of iCPET as a key methodology for diagnosing heart failure with preserved ejection fraction and exercise-induced pulmonary hypertension as occult causes of exercise limitation, but there is little information available outlining the methodology to use this diagnostic test in clinical practice. To bridge this knowledge gap, the operational protocol for iCPET at our institution is discussed in detail. In turn, a standardized iCPET protocol may provide a common framework to describe the evolving understanding of mechanism(s) that limit exercise capacity and to facilitate research efforts to define novel treatments in these patients.

Rest and exercise echocardiography for early detection of pulmonary hypertension.

Early detection of pulmonary hypertension (PH) is essential to ensure that patients receive timely and appropriate treatment for this progressive disease. Rest and exercise echocardiography has been used to screen patients in an attempt to identify early stage PH. However, current PH guidelines recommend against exercise tests because of the lack of evidence. We reviewed previous studies to discuss the current standpoint concerning rest and exercise echocardiography in PH. Around 20 exercise echocardiography studies were included to assess the cutoff value for exercise-induced pulmonary hypertension (EIPH). Approximately 40 exercise echocardiography studies were also included to evaluate the pulmonary artery pressure-flow relationship as assessed by the slope of the mean pulmonary artery pressure and cardiac output (ΔmPAP/ΔQ). There were several EIPH and ΔmPAP/ΔQ reference values in individuals with pulmonary vascular disease. We believed that assessing the ΔmPAP/ΔQ makes sense from a physiological standpoint, and the clinical value should be confirmed in future studies. Exercise echocardiography is an appealing alternative in PH. Further studies are needed to assess the prognostic value of the pulmonary artery pressure-flow relationship in high-risk subjects.

Cardiovascular outcome in systemic sclerosis

Objectives Cardiovascular involvement is recognized as a poor prognostic factor in systemic sclerosis (SSc). The aim of this study was to evaluate the usefulness of nailfold video-capillaroscopy (NVC), brain natriuretic peptide (BNP) blood level and exercise echocardiography to predict the occurrence of cardiovascular events in SSc.Methods We prospectively enrolled 65 patients with SSc (age 54 ± 14 years, 30% female) followed in CHU Sart-Tilman, Liège, Belgium. All patients underwent graded semi-supine exercise echocardiography. Both baseline resting pulmonary hypertension (PH) and PH during follow-up (FUPH) were defi ned as systolic pulmonary arterial pressure (sPAP) > 35 mmHg, and exercise-induced PH (EIPH) as sPAP > 50 mmHg during exercise.Results EIPH was present in 21 patients. During FU (27 ± 18 months), 13 patients developed FUPH and 9 presented cardiovascular complications. Patients with cardiovascular events were signifi cantly older (63 ± 14 vs 52 ± 13 years; P = 0.03), presented more frequently NVC grade > 2 (89 vs 43%; P = 0.009), had higher resting and exercise sPAP (30 ± 6 vs 24 ± 6; P = 0.007 and 57 ± 13 vs 44 ± 13 vs mmHg; P = 0.01, respectively), and higher BNP blood level (112 ± 106 vs 26 ± 19 pg/ml; P = 0.0001). After adjustment for age and gender, NVC grade > 2 (ß = 2.4 ± 1.1; P = 0.03), EIPH (ß = 2.30 ± 1.13; P = 0.04), FUPH (ß = 0.24 ± 0.09; P = 0.01 and ß = 3.52 ± 1.16; P = 0.002, respectively;) and BNP (ß = 0.08 ± 0.04; P = 0.02) were independent predictors of CV events. Beyond age, an incremental value of EIPH, BNP and NVC grade > 2 was predictive of cardiovascular events (P < 0.001).Conclusion Cardiovascular complications are not rare in SSc (18%). NVC, BNP blood level assessment and exercise echocardiography could be useful tools to identify patients at risk of SSc.

Exercise-induced pulmonary hypertension: at last!

Two studies in the September issue of the ERJ support the recognition of exercise-induced pulmonary hypertension http://ow.ly/Pk7xn

Pulmonary hemodynamic profile in chronic obstructive pulmonary disease.

IntroductionFew data are available in regards to the prevalence of pulmonary hypertension (PH) in the broad spectrum of COPD. This study was aimed at assessing the prevalence of PH in a cohort of COPD patients across the severity of airflow limitation, and reporting the hemodynamic characteristics at rest and during exercise.MethodsWe performed a retrospective analysis on COPD patients who underwent right-heart catheterization in our center with measurements obtained at rest (n=139) and during exercise (n=85). PH was defined as mean pulmonary artery pressure (mPAP) ≥25 mmHg and pulmonary capillary wedge pressure <15 mmHg. Exercise-induced PH (EIPH) was defined by a ratio of ΔmPAP/Δcardiac output >3.ResultsPH was present in 25 patients (18%). According to the Global Initiative for Chronic Obstructive Lung Disease (GOLD) classification, PH prevalence in GOLD 2 was 7% (3 patients); 25% (14 patients) in GOLD 3; and 22% (8 patients) in GOLD 4. Severe PH (mPAP ≥35 mmHg) was identified in four patients (2.8%). Arterial partial oxygen pressure was the outcome most strongly associated with PH (r=−0.29, P<0.001). EIPH was observed in 60 patients (71%) and had a similar prevalence in both GOLD 2 and 3, and was present in all GOLD 4 patients. Patients with PH had lower cardiac index during exercise than patients without PH (5.0±1.2 versus 6.7±1.4 L/min/m2, respectively; P=0.001).ConclusionPH has a similar prevalence in COPD patients with severe and very-severe airflow limitation, being associated with the presence of arterial hypoxemia. In contrast, EIPH is highly prevalent, even in moderate COPD, and might contribute to limiting exercise tolerance.

Exercise-Induced Pulmonary Artery Hypertension in a Patient with Compensated Cardiac Disease: Hemodynamic and Functional Response to Sildenafil Therapy

We describe the case of a 54-year-old man who presented with exertional dyspnea and fatigue that had worsened over the preceding 2 years, despite a normally functioning bioprosthetic aortic valve and stable, mild left ventricular dysfunction (left ventricular ejection fraction, 0.45). His symptoms could not be explained by physical examination, an extensive biochemical profile, or multiple cardiac and pulmonary investigations. However, abnormal cardiopulmonary exercise test results and a right heart catheterization-combined with the use of a symptom-limited, bedside bicycle ergometer-revealed that the patient's exercise-induced pulmonary artery hypertension was out of proportion to his compensated left heart disease. A trial of sildenafil therapy resulted in objective improvements in hemodynamic values and functional class.

Influence of Left Ventricular Diastolic Function on Exercise-induced Pulmonary Hypertension in Patients with Systemic Sclerosis

Background: Exercise-induced pulmonary hypertension (EIPH) can be caused not only by pulmonary vas‐ culopathy, but also by a significant increase in left ventricular (LV) filling pressure. This study evaluated the influence of LV diastolic function on EIPH in patients with systemic sclerosis (SSc). Methods: The study included 222 SSc patients (age 58.9 ± 13.1 years, 85% female) and 30 controls with similar age distribution. In all patients, systolic pulmonary artery pressure (SPAP) and the ratio of early diastolic transmitral flow velocity to early diastolic mitral annular velocity (E/e’), as an index of LV filling pressure, were measured before and after exercise Doppler echocardiography using a Master’s two-step. Results: The patients with SSc were classified into either the non-EIPH (SPAP < 50 mmHg, n = 123, 56%) or EIPH (SPAP ≥ 50 mmHg, n = 97, 44%) group. No significant change from E/e’ at rest to E/e’ post exercise was found in the controls (8.8 and 9.6), whereas significant changes were found in the non-EIPH (8.7 and 9.5 p < 0.0001) and EIPH groups (10.3 and 12.6, p < 0.0001). In addition, significant differences in E/e’ at rest and post exercise were found between the non-EIPH and EIPH groups (p <0.0001). Multivariate logistic regression analysis identified age (odds ratio, 1.036; 95% confidence interval, 1.015–1.058, p < 0.0001) and E/e’ (odds ratio, 1.154; 95% confidence interval, 1.066–1.246, p < 0.0001) as independent predictors of EIPH. Conclusions: Our results suggest that approximately one third of SSc patients have EIPH. LV diastolic function might be associated with EIPH in patients with SSc.

Errata: Influence of Left Ventricular Diastolic Function on Exercise-induced Pulmonary Hypertension in Patients with Systemic Sclerosis [J. St. Marianna Univ Vol.6, pp. 131-139, 2015

1) In the authors’ list, Dr. Yamasaki, Dr. Yamada and Dr. Ozaki were omitted by mistake. Corrected authors’ names and affi liations are listed as below. Manabu Takai1, Kengo Suzuki1, Masaki Izumo1, Kanako Teramoto1,Yukio Sato1, Maya Tsukahara1, Keisuke Minami1, Shingo Kuwata1, Ryo Kamijima1, Kei Mizukoshi1, Seisyou Kou1, Akio Hayashi1, Yoshioki Yamasaki2, Hidehiro Yamada2, Shoichi Ozaki2, Sachihiko Nobuoka3, Yoshihiro J. Akashi1 1. Division of Cardiology, Department of Internal Medicine, St. Marianna University School of Medicine 2. Division of Rheumatology and Allergy, Department of Internal Medicine, St. Marianna University School of Medicine 3. Department of Laboratory Medicine, St. Marianna University School of Medicine

Ask the Expert: What Is the Utility of Evaluating Patients for Exercise-Induced Pulmonary Hypertension?

Ask the Expert: What Is the Utility of Evaluating Patients for Exercise-Induced Pulmonary Hypertension?