Health literacy in patients with pulmonary embolism: development and validation of the HeLP (Health Literacy in Pulmonary Embolism)-Questionnaire.

Background: Pulmonary embolism (PE) is a common cardiovascular disease and health literacy is necessary to deal with its consequences after the acute event. The aim of this study was to develop and validate a new questionnaire to measure PE-specific health literacy. Methods: A mixed-methods design with qualitative and quantitative elements was used in the development process. A literature review about health literacy concepts and instruments and interviews with patients with PE and clinicians were conducted. Quantitative analyses included factor analyses, item response theory with a graded partial credit model, and reliability analyses in different test and validation samples. Furthermore, convergent and known-groups validity and responsiveness were assessed. Results: The qualitative results supported a concept of PE-related health literacy with four main topics: dealing with PE-related health information, disease management, health-related selfcare, and social support. An initial item pool of 91 items was developed. Further interviews and an online survey with patients with PE (n = 1,013) were used to reduce the number of items and to confirm structural validity. Confirmatory factor analyses in the final evaluation study with patients with PE (n = 238) indicated a good model fit of the four-factor structure. The Health Literacy in Pulmonary Embolism (HeLP)-Questionnaire showed good reliability (Cronbach's alpha: 0.82 to 0.90). All four subscales were responsive toward receiving a brochure with PE-related health information. Conclusion: The newly developed German HeLP Questionnaire comprises 23 items in four domains and showed good psychometric properties. Further evaluation of the questionnaire in different samples of patients with PE is needed.

Depression and anxiety up to two years after acute pulmonary embolism: Prevalence and predictors.

INTRODUCTION: Pulmonary embolism (PE) is an acute life-threatening event. Besides known physical long-term consequences such as persistent dyspnoea or reduced physical performance, less attention is given to the emotional experience. METHODS: We used data from patients with PE of the 'Lungenembolie Augsburg (LEA)' cohort study at University Hospital Augsburg. Baseline characteristics were collected during hospital stay and participants received postal questionnaires 3, 6, 12, and 24 months after their PE event. Mental problems were assessed by the Hospital Anxiety and Depression Scale (HADS). Differences in baseline characteristics in patients with or without depression or anxiety at 3 months were tested. Linear mixed models were built to explore long-term effects. RESULTS: About one-in-five of the 297 patients suffered from depressive or anxiety symptoms after PE. Patients with depressiveness 3 months after PE were found to be significantly older, had a higher simplified pulmonary embolism severity index (sPESI), higher education level, more frequently previous depression, lower oxygen saturation, and a longer hospital stay. Linear mixed models revealed significant associations of age, history of depression and sPESI with HADS depression score, and symptoms of dyspnoea with HADS anxiety score after PE. While the association with sPESI decreased over time, persistent dyspnoea and limitations in daily life showed constant associations over the two-year time period for both, depression and anxiety. CONCLUSIONS: The findings highlight depression and anxiety to be common in patients with PE and reveal possible predictors. Careful monitoring the mental health of patients with PE is needed for early detection and intervention.

Lung perfusion assessed by SPECT/CT after a minimum of three months anticoagulation therapy in patients with SARS-CoV-2-associated acute pulmonary embolism: a retrospective observational study.

BACKGROUND: Anticoagulant treatment is recommended for at least three months after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-related acute pulmonary embolism (PE), but the persistent pulmonary clot burden after that time is unknown. METHODS: Lung perfusion was assessed by ventilation-perfusion (V/Q) SPECT/CT in 20 consecutive patients with SARS-CoV-2-associated acute PE after a minimum of three months anticoagulation therapy in a retrospective observational study. RESULTS: Remaining perfusion defects after a median treatment period of six months were observed in only two patients. All patients (13 men, seven women, mean age 55.6 ± 14.5 years) were on non-vitamin K direct oral anticoagulants (DOACs). No recurrent venous thromboembolism or anticoagulant-related bleeding complications were observed. Among patients with partial clinical recovery, high-risk PE and persistent pulmonary infiltrates were significantly more frequent (p < 0.001, respectively). INTERPRETATION: Temporary DOAC treatment seems to be safe and efficacious for resolving pulmonary clot burden in SARS-CoV-2-associated acute PE. Partial clinical recovery is more likely caused by prolonged SARS-CoV-2-related parenchymal lung damage rather than by persistent pulmonary perfusion defects.

The German version of the Pulmonary Embolism Quality of Life (PEmb-QoL) questionnaire: reliability, responsiveness and structural validity.

PURPOSE: The Pulmonary Embolism Quality of Life (PEmb-QoL) questionnaire is the only existing disease-specific instrument for measuring quality of life after pulmonary embolism (PE). It includes six dimensions: frequency of complaints, limitations in activities of daily living, work-related problems, social limitations, intensity of complaints and emotional complaints. The present study aimed to determine the psychometric properties including responsiveness and structural validity of the German version. METHODS: The analysis used data from participants of the LEA cohort study at University Hospital Augsburg. The PEmb-QoL was administered via postal surveys 3, 6 and 12 months post-PE. Internal consistency and test-retest reliability were evaluated by calculating Cronbach's alpha and intra-class correlation coefficients (ICC). Standardized response means (SRM) were calculated for investigating responsiveness. For evaluating the fit of the factor structure, confirmatory factor analysis (CFA) was conducted. RESULTS: Overall, we used data from 299 patients 3 months after PE. Cronbach's alpha (0.87-0.97) and ICC (0.53-0.90) were in an acceptable to good range. SRM scores showed good responsiveness of all dimensions. CFA revealed the four-factor model including one general factor to have a good model fit. CONCLUSION: Despite existing floor effect, most standard criteria of reliability and validity were met and indications for appropriateness of the PEmb-QoL summary score could be found. Apart from some restrictions concerning the factor structure and the dimension of social limitations, our results support the use of the PEmb-QoL questionnaire for evaluating PE-specific quality of life. Future studies should seek replication in different samples to ensure generalizability of the findings.

COVID-19 risk perceptions, worries and preventive behaviors in patients with previous pulmonary embolism.

INTRODUCTION: The presence of conditions, such as cardiovascular or chronic lung diseases, was reported to be associated with more severe cases of COVID-19. It is, however, so far unclear how patients with a history of pulmonary embolism (PE) perceive their individual COVID-19 risk. Moreover, their worries and preventive behaviors and their associations with risk perception are unknown. MATERIALS AND METHODS: A postal survey was conducted in April 2020, including participants with previous PE from the German "Lungenembolie Augsburg" (LEA) cohort study. The questionnaire contained items on COVID-19 knowledge, risk perception (infection likelihood, susceptibility, dangerousness), information sources and satisfaction with information, individual assignment to a high risk group due to pre-existing conditions, worries, infection likelihood, and implementation of preventive behaviors. RESULTS: From the 185 respondents, 71.7% assigned themselves to a high risk group in terms of developing a severe case of COVID-19. The likelihood of being infected was rated as verylow/low by 82.3% and the susceptability by 37.8%. A considerable percentage of patients expected a very high/high infection risk in a hospital (48.3%) or at a doctor's practice (37.9%). Major sources of information were the patients' general practitioners (48.9%) and the internet (31.5%). Assignment to a high risk group (ß = 1.04) and uncertainty in terms of assignment (ß = 1.26) were significantly (p = 0.01) associated with a higher level of health-related worries. CONCLUSIONS: Most patients with previous PE feel that they belong to a high risk group in terms of severe illness from COVID-19. Support in coping with their individual COVID-19 risk is warranted.

Right-to-left Ventricular Diameter Ratio At Computed Tomographic Pulmonary Angiography in Patients with Acute Pulmonary Embolism and Obstructive Sleep Apnea.

PURPOSE: Right ventricular (RV) dysfunction in acute pulmonary embolism (PE) is a critical determinant of outcome. Obstructive sleep apnea (OSA) is a common comorbidity of PE and might also affect RV function. Therefore, we sought to investigate RV dysfunction in PE patients in proportion to the severity of OSA by evaluating the right-to-left ventricular (RV/LV) diameter ratio on computed tomographic pulmonary angiography (CTPA). MATERIALS AND METHODS: 197 PE patients were evaluated for sleep-disordered breathing by portable monitoring and nocturnal polysomnography. RV dilatation was defined as an RV/LV diameter ratio of ⩾ 1.0. RESULTS: RV dilatation was significantly more frequent in OSA patients compared to study participants without OSA (66.4% vs 49.1%, P = .036). Elevated troponin I values, indicating myocardial injury due to acute, PE-related RV strain, were significantly more frequent in OSA patients with an apnea-hypopnea index (AHI) ⩾ 15/h compared to those with an AHI < 15/h (62.1% vs 45.8%, P = .035). However, RV dysfunction documented by the RV/LV diameter ratio on CTPA was not significantly associated with the severity of OSA in multivariable regression analysis. CONCLUSION: Patients with moderate or severe OSA might compensate acute, PE-related RV strain better, as they are adapted to repetitive right heart pressure overloads during sleep.

The lived experience with pulmonary embolism: A qualitative study using focus groups.

BACKGROUND: Pulmonary embolism (PE) is the third most common cause of cardiovascular death. However, comprehensive knowledge on the lived experience of patients with PE is lacking so far. The objective of this study was to fill this gap using a qualitative research approach. METHODS: A qualitative study using focus group methodology was conducted. Sampling of patients followed the maximum variation strategy. Sample size was determined by saturation. The patients were presented eight questions, which asked for their experiences in terms of prodromal and acute symptoms, changes of physical and mental well-being, daily life and social life, and experiences with PE medication and treatment. The focus group discussions were digitally recorded and transcribed verbatim. The constant comparative method was used for data analysis. RESULTS: Five focus groups with n = 18 participants (50% female, median age 56 years) in total were performed. Major identified themes were: (1) progressing dyspnea and pain as major prodromal and acute symptoms, (2) persisting dyspnea and loss of physical fitness, (3) depression, fears and threat monitoring, (4) exhaustion which improves over time, (5) social contacts ranging between ignorance and overprotection, (6) anticoagulants as lifesavers and threat, (7) quick versus delayed diagnosis, (8) left alone by health care providers, and (9) unsupportive health care system. CONCLUSION: PE may be associated with considerable mental health problems and the existing health care system is experienced as not supportive by a number of patients. Further results from larger, quantitative studies are needed to estimate the extent of the identified problems.

Impact of acyclovir use on survival of patients with ventilator-associated pneumonia and high load herpes simplex virus replication.

BACKGROUND: Herpes simplex virus (HSV) replication can be detected in the respiratory secretions of a high proportion of ventilated intensive care unit (ICU) patients. However, the clinical significance remains poorly defined. We investigated whether patients with ventilator-associated pneumonia not responding to antibiotics and in whom high levels of HSV could be detected in respiratory secretions benefit from acyclovir treatment. METHODS: Respiratory secretions (bronchoalveolar lavage fluid or tracheal aspirates) were tested for HSV replication by quantitative real-time PCR. ICU survival times, clinical parameters, and radiographic findings were retrospectively compared between untreated and acyclovir treated patients with high (> 105 HSV copies/mL) and low (103-105 HSV copies/mL) viral load. RESULTS: Fifty-seven low and 69 high viral load patients were identified. Fewer patients with high viral load responded to antibiotic treatment (12% compared to 40% of low load patients, p = 0.001). Acyclovir improved median ICU survival (8 vs 22 days, p = 0.014) and was associated with a significantly reduced hazard ratio for ICU death (HR = 0.31, 95% CI 0.11-0.92, p = 0.035) in high load patients only. Moreover, circulatory and pulmonary oxygenation function of high load patients improved significantly over the course of acyclovir treatment: mean norepinephrine doses decreased from 0.05 to 0.02 µg/kg body weight/min between days 0 and 6 of treatment (p = 0.049), and median PaO2/FiO2 ratio increased from 187 to 241 between day 3 and day 7 of treatment (p = 0.02). Chest radiographic findings also improved significantly (p < 0.001). CONCLUSIONS: In patients with ventilator-associated pneumonia, antibiotic treatment failure, and high levels of HSV replication, acyclovir treatment was associated with a significantly longer time to death in the ICU and improved circulatory and pulmonary function. This suggests a causative role for HSV in this highly selected group of patients.

Obstructive sleep apnea is associated with pulmonary artery thrombus load, disease severity, and survival in acute pulmonary embolism.

INTRODUCTION: Obstructive sleep apnea (OSA) may have prothrombotic effects. OBJECTIVE: To investigate the effect of OSA on disease severity, pulmonary artery thrombus load, and prognosis in patients with acute pulmonary embolism (PE). METHODS: In 101 PE patients, disease severity was determined by the simplified PE severity index (sPESI) score, pulmonary artery thrombus load was quantified by the pulmonary artery obstruction index (PAOI), and sleep-disordered breathing was evaluated by nocturnal polygraphy. RESULTS: Obstructive sleep apnea patients with an apnea-hypopnea index (AHI) ≥ 15/h cohort were significantly older (p < 0.001) and had significantly lower oxygen saturations (p = 0.008) when acute PE was diagnosed. The sPESI scores (p < 0.001), the PAOI (p = 0.005) and the N-terminal pro-brain-type natriuretic peptide (NT-proBNP) values (p = 0.009), were significantly higher in the AHI ≥ 15/h subgroup. In a multivariate regression analysis, the AHI remains a significant predictor for sPESI scores ≥ 1 (p = 0.003), increased NT-proBNP levels (p = 0.047), and elevated PAOI (p = 0.032). During the median follow-up time of 53 (interquartile range 38-70) months, all-cause and cardiovascular-related mortality was significantly higher in the AHI ≥ 15/h cohort (p = 0.004 and p = 0.015, respectively). CONCLUSIONS: Obstructive sleep apnea is associated with pulmonary artery thrombus load, disease severity, and survival in acute PE possibly due to its prothrombotic effects.

Long-term outcomes in patients with acute pulmonary embolism after in-hospital treatment: study protocol of the prospective Lungenembolie Augsburg Studie (LEA study).

INTRODUCTION: Acute pulmonary embolism (PE) is a frequent life-threatening event and an important cause of hospitalisation, morbidity and mortality worldwide. Limited information on the long-term course of PE patients is available so far. The Lungenembolie Augsburg study will provide a view on the predisposing and PE-provoking factors, diagnostic procedures and short as well as long-term treatment options. Especially, the data on the long-term course of the disease-in combination with omics data obtained in biospecimens-will generate new knowledge regarding triggers, disease progression, treatment, long-term sequelae, prognosis and prevention of disease recurrence. METHODS AND ANALYSIS: In this prospective study, we will include about 1000 patients admitted to the university hospital of Augsburg, aged 18 years and older with a confirmed diagnosis of acute PE. At baseline, demographic information, symptoms on presentation, delay in diagnosis, predisposing and PE-provoking factors, comorbidity, quality of life, symptoms of anxiety and depression, information on invasive and non-invasive treatment procedures, complications and laboratory parameters will be collected. During the hospital stay, 30 mL blood will be collected from the patients, processed, aliquoted and frozen at -80°C. In a subgroup of patients, an eight-channel polygraphy will be carried out to assess sleep-disordered breathing. All study participants will be followed up for 60 months via postal questionnaires or telephone interviews after hospital discharge. Long-term survival, bleeding complications and PE recurrence during the follow-up are the primary study outcomes. To identify risk factors and determinants associated with these outcomes, confounder-adjusted Cox-regressions will be used for modelling and to estimate relative risks. Effect modification by age and sex will be examined. ETHICS AND DISSEMINATION: The study protocol was approved by the Ethics Committee of the Ludwig-Maximilians-Universität München (Date of approval: 1 August 2017, Reference number: 17-378). Study results will be presented at national and international conferences and published in peer-reviewed scientific journals.

D-Dimer Predicts Disease Severity but Not Long-Term Prognosis in Acute Pulmonary Embolism.

D-dimer might be correlated with prognosis in pulmonary embolism (PE). The predictive value of plasma D-dimer for disease severity and survival was investigated in the lowest and highest D-dimer quartile among 200 patients with PE. Patients with high D-dimers were significantly more often hypotensive (P = .001), tachycardic (P = .016), or hypoxemic (P = .001). Pulmonary arterial obstruction index (PAOI) values were significantly higher in the high D-dimer quartile (P < .001). Elevated troponin I (TNI) levels (P < .001), simplified PE severity indices ≥1 (P < .001), right-to-left ventricular (RV/LV) diameter ratios ≥1 (P < .001), and thrombolysis (P = .001) were more frequent in the high D-dimer quartile. D-dimer was associated with RV/LV ratios ≥1 (P = .021), elevated PAOI (P < .001) or TNI levels (P < .001), hypotension (P < .001), tachycardia (P = .003), and hypoxemia (P < .001), but not with long-term all-cause mortality. D-dimer predicts disease severity but not long-term prognosis in acute PE, possibly due to a more aggressive treatment strategy in severely affected patients.

Successful long-term treatment of persistent pulmonary air leak in pneumocystis jirovecii pneumonia by unidirectional endobronchial valves.

Spontaneous pneumothorax is a rare complication of pneumocystis jirovecii pneumonia. We report a patient with pneumocystis jirovecii pneumonia and therapy-refractory, right-sided pneumothorax due to persistent air leak (PAL) despite prolonged chest tube placement and multiple pleurodesis attempts. Due to the patient's morbidity, we evaluated if the PAL can be sealed by unidirectional endobronchial valves (EBVs). After occlusion of the right upper lobe by a balloon catheter, the air leak flow-rate decreased from 800 ml/min to 250 ml/min. Zephyr EBVs (ZEBVs) were placed in the segmental right upper lobe bronchi and subsequently, a complete resolution of the pneumothorax was noted. During 30 months of follow-up, neither recurrence of pneumothorax nor any adverse events of EBV treatment were noted. We conclude that ZEBV placement might be an effective and well-tolerated treatment option for PAL secondary to pneumocystis jirovecii pneumonia with promising long-term results.

Is acute pulmonary embolism more severe in the presence of obstructive sleep apnea? Results from an observational cohort study.

Obstructive sleep apnea (OSA) might influence disease severity in acute pulmonary embolism (PE). 253 survivors of acute PE were evaluated for sleep-disordered breathing by portable monitoring and nocturnal polysomnography. PE patients with an apnea-hypopnoea index (AHI) ≥ 15/h were significantly older (p < 0.001), had significantly impaired renal (p < 0.001) and left ventricular functions (p = 0.003), showed significantly elevated troponin I (p = 0.005) and D-dimer levels (p = 0.024), were hospitalised significantly longer (p < 0.001), and had significantly elevated PE severity scores (p = 0.015). Moderate or severe OSA was significantly (p = 0.006) more frequent among intermediate- and high-risk PE patients (81.0%) compared to the low-risk PE cohort (16.3%). Multiple logistic regression analysis revealed that PE patients in the AHI ≥ 15/h cohort were at significant risk for myocardial injury (p = 0.015). Based on clinical risk stratification models, patients with no relevant OSA syndrome tended to be at a lower risk for short-term mortality (p = 0.068). Acute PE might present more severely in OSA patients, possibly due to nocturnal hypoxemia or OSA-related hypercoagulability.

The prevalence of sleep-disordered breathing among survivors of acute pulmonary embolism.

BACKGROUND: Sleep-disordered breathing (SDB) is associated with prothrombotic effects that could lead to venous thromboembolic diseases. OBJECTIVE: The objective of this study is to clarify the prevalence of SDB among survivors of pulmonary embolism (PE). METHODS: One hundred six consecutive PE patients were prospectively evaluated by portable monitoring (PM). Nocturnal polysomnography was performed in all subjects who were diagnosed by PM to have an apnoea-hypopnoea index (AHI) > 15/h or evidence of increased daytime sleepiness. RESULTS: The overall SDB prevalence in the study population was 58.5 %. Mild obstructive sleep apnoea (OSA) was diagnosed in 35.8 % of patients. Of the subjects, 12.3 % suffered from moderate OSA. In 10.4 % of study participants, OSA was found to be severe. High-risk PE was significantly more frequent among subjects with an AHI > 15/h (p = 0.005). CONCLUSION: OSA is a common comorbidity of PE and possibly represents an additional risk factor for hemodynamic instability in PE patients.

Can coronary artery anomalies be detected on CT calcium scoring studies?

PURPOSE: To determine whether coronary artery anomalies can be detected on noncontrast computed tomography (CT) coronary artery calcium scoring (CCS) studies. MATERIALS AND METHODS: A total of 126 patients (mean age 62 years; 35 women) underwent noncontrast CCS and contrast enhanced coronary CT angiography (cCTA). Thirty-three patients were diagnosed with a coronary anomaly on cCTA, whereas coronary anomalies were excluded in 93. Two observers (reader 1 [R1] and reader 2 [R2]), blinded to patient information independently evaluated each CCS study for: 1) visibility of coronary artery origins, 2) detection of coronary anomalies, and 3) benign or malignant (ie, interarterial) course. Using cCTA as the reference standard, sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of CCS studies for detecting coronary anomalies were calculated. RESULTS: Of the 33 coronary anomalies, 16 were benign and 17 malignant. Based on noncontrast CCS studies, R1 and R2 correctly identified the left main origin in 123/126 (97.6%) and 121/126 (96%) patients; the left anterior descending origin in 125/126 (99.2%) and 122/126 (96.8%); the circumflex origin in 120/126 (95.2%) and 105/126 (83.3%); and the right coronary artery origin in 117/126 (92.9%) and 103/126 (81.7%), respectively. R1 and R2 identified 34 and 27 coronary anomalies and classified 19 and 15 as malignant, respectively. Interobserver reproducibility for detection of coronary anomalies was good (k = 0.76). Interobserver agreement for detection of malignant variants was even stronger (k = 0.80). On average, coronary artery anomalies were diagnosed with 85.2% sensitivity, 96.4% specificity, 90.5% PPV, and 94.1% NPV on noncontrast CCS studies. CONCLUSION: Benign and malignant coronary artery anomalies can be detected with relatively high accuracy on noncontrast-enhanced CCS studies. CCS studies should be reviewed for signs of coronary artery anomalies in order to identify malignant variants with possible impact on patient management.

Drug induced interstitial lung disease.

With an increasing number of therapeutic drugs, the list of drugs that is responsible for severe pulmonary disease also grows. Many drugs have been associated with pulmonary complications of various types, including interstitial inflammation and fibrosis, bronchospasm, pulmonary edema, and pleural effusions. Drug-induced interstitial lung disease (DILD) can be caused by chemotherapeutic agents, antibiotics, antiarrhythmic drugs, and immunosuppressive agents. There are no distinct physiologic, radiographic or pathologic patterns of DILD, and the diagnosis is usually made when a patient with interstitial lung disease (ILD) is exposed to a medication known to result in lung disease. Other causes of ILD must be excluded. Treatment is avoidance of further exposure and systemic corticosteroids in patients with progressive or disabling disease.

Ventilatory efficiency testing as prognostic value in patients with pulmonary hypertension.

BACKGROUND: Increased ventilatory response has been shown to have a high prognostic value in patients with chronic heart failure. Our aim was therefore to determine the ventilatory efficiency in pulmonary arterial hypertension and chronic thromboembolic pulmonary hypertension by cardiopulmonary exercise testing (CPET) identifying PH-patients with increased risk for death within 24 months after evaluation. METHODS: 116 patients (age: 64 ± 1 years) with a mean pulmonary arterial pressure of 35 ± 1 mmHg underwent CPET and right heart catheterization. During a follow-up of 24 months, we compared the initial characteristics of survivors (n = 87) with nonsurvivors (n = 29). RESULTS: Significant differences (p ≤ 0.005) between survivors and nonsurvivors existed in ventilatory equivalents for oxygen (42.1 ± 2.1 versus 56.9 ± 2.6) and for carbon dioxide (Ve/VCO2) (47.5 ± 2.2 versus 64.4 ± 2.3). Patients with peak oxygen uptake ≤ 10.4 ml/min/kg had a 1.5-fold, Ve/VCO2 ≥ 55 a 7.8-fold, alveolar-arterial oxygen difference ≥ 55 mmHg a 2.9-fold, and with Ve/VCO2 slope ≥ 60 a 5.8-fold increased risk of mortality in the next 24 months. CONCLUSIONS: Our results demonstrate that abnormalities in exercise ventilation powerfully predict outcomes in PH. Consideration should be given to add clinical guidelines to reflect the prognostic importance of ventilatory efficiency parameters in addition to peak VO2.

Detection of exercise-induced pulmonary arterial hypertension by cardiopulmonary exercise testing.

BACKGROUND: The pulmonary arterial pressure (PAP) response to exercise may provide a tool for the early detection of pulmonary arterial hypertension (PAH). Therefore, an accurate noninvasive method for evaluating exercise-induced PAH (EIPAH) is desirable. HYPOTHESIS: We sought to examine if cardiopulmonary exercise testing (CPET) is able to indicate EIPAH. METHODS: Fifty-three patients aged 67.1 ± 1.7 years (37 female, 16 male) with borderline PAH (resting mean PAP 21-24 mm Hg) performed CPET and right heart catheterization at rest and during handgrip testing. RESULTS: When comparing patients with an exercise-induced mean PAP ≥ mm Hg (group A, n = 24) and subjects with an exercise-induced mean PAP <35 mm Hg (group B, n = 29), group A had a significantly lower mean aerobic capacity (15.2 ± 1.2 vs 19.7 ± 1.2 mL/min/kg; P = 0.02), higher ventilatory equivalents for oxygen at the anaerobic threshold (34.3 ± 1.5 vs 29.9 ± 1.1; P = 0.02), a widening of the mean alveolar-arterial oxygen difference (37.8 ± 3.0 vs 26.8 ± 2.4 mm Hg; P = 0.007), an elevated mean functional dead space ventilation (29.5 ± 2.7 vs 21.2 ± 1.7%; P = 0.008), and a higher mean arterial to end-tidal carbon dioxide gradient at peak exercise (3.7 ± 0.9 vs 0.4 ± 0.8 mm Hg; P = 0.007). CONCLUSIONS: EIPAH is characterized by a decreased ventilatory efficiency due to ventilation to perfusion inequalities. CPET may be useful for the identification of EIPAH and serve to diagnose PAH at an early stage.