Unexplained Exertional Dyspnea Research Articles

Bronchoalveolar Lavage Fluid Cytology of Deployed Military Personnel With Chronic Respiratory Symptoms From the STAMPEDE III Study.

Deployed military personnel may be at risk for developing acute and chronic lung disease. Prior studies of this patient population have revealed that unexplained exertional dyspnea is the most common diagnosis despite an extensive evaluation. There is a concern that an occult disorder may be affecting this population. This study evaluated the role for bronchoalveolar lavage (BAL) fluid analysis in the evaluation of chronic deployment-associated dyspnea. Military personnel who reported chronic respiratory symptoms were evaluated as part of the Study of Active Duty Military for Pulmonary Disease Related to Environmental Deployment Exposures III study. Participants underwent bronchoscopy with BAL as part of a standardized evaluation. A total of 308 patients with a mean age of 38 ± 8.6 years underwent bronchoscopy with BAL. BAL cell-count percentages of macrophages, lymphocytes, neutrophils, and eosinophils were: 76.2 ± 17.0%, 16.3 ± 13.4%, 6.6 ± 8.9%, and 0.9 ± 3.2%, respectively. There was no clear differentiation between groups based on increases in lymphocyte counts (P = .640), although lymphocyte values were more elevated (21.4 ± 12.1%) in the interstitial lung disease category. Neutrophil counts (6.6 ± 8.9%) were elevated compared to the reported normal reference values and were increased in the isolated pulmonary function test abnormality (9.4 ± 11.6%), large airway disorder (10.0 ± 7.5%), miscellaneous (10.9 ± 20.2%), and obstructive lung disease (11.0 ± 15.6%) groups. Eosinophil counts were within normal limits (0.9 ± 3.2%) and showed no differences between groups (P = .545); asthma patients trended higher (1.6 ± 5.7%). BAL counts for the exertional dyspnea group were within normal reference values and showed no differences from the entire cohort. The addition of BAL cytology did not help differentiate those patients with unexplained dyspnea from other etiologies.

Repetitive sulfur dioxide exposure in mice models post-deployment respiratory syndrome.

Soldiers deployed to Iraq and Afghanistan have a higher prevalence of respiratory symptoms than nondeployed military personnel and some have been shown to have a constellation of findings on lung biopsy termed post-deployment respiratory syndrome (PDRS). Since many of the subjects in this cohort reported exposure to sulfur dioxide (SO2), we developed a model of repetitive exposure to SO2 in mice that phenocopies many aspects of PDRS, including adaptive immune activation, airway wall remodeling, and pulmonary vascular (PV) disease. Although abnormalities in small airways were not sufficient to alter lung mechanics, PV remodeling resulted in the development of pulmonary hypertension and reduced exercise tolerance in SO2-exposed mice. SO2 exposure led to increased formation of isolevuglandins (isoLGs) adducts and superoxide dismutase 2 (SOD2) acetylation in endothelial cells, which were attenuated by treatment with the isoLG scavenger 2-hydroxybenzylamine acetate (2-HOBA). In addition, 2-HOBA treatment or Siruin-3 overexpression in a transgenic mouse model prevented vascular remodeling following SO2 exposure. In summary, our results indicate that repetitive SO2 exposure recapitulates many aspects of PDRS and that oxidative stress appears to mediate PV remodeling in this model. Together, these findings provide new insights regarding the critical mechanisms underlying PDRS.NEW & NOTEWORTHY We developed a mice model of "post-deployment respiratory syndrome" (PDRS), a condition in Veterans with unexplained exertional dyspnea. Our model successfully recapitulates many of the pathological and physiological features of the syndrome, revealing involvement of the ROS-isoLGs-Sirt3-SOD2 pathway in pulmonary vasculature pathology. Our study provides additional knowledge about effects and long-term consequences of sulfur dioxide exposure on the respiratory system, serving as a valuable tool for future PDRS research.

Left ventricular mass index versus results of diastolic stress echocardiography in patients with heart failure with preserved ejection fraction

Background: Left ventricular mass and left ventricular mass index (LVMI) is an index reflecting the thickness of the cardiac muscle, and the E/e’ ratio is a specific indicator for identifying increased left ventricular filling pressure. Limited data exist regarding the prognostic value of incorporating left ventricular mass index in heart failure with preserved ejection fraction (HFpEF). Aim: This study aimed to assess diagnostic value of LVMI at rest versus diastolic stress echo results in patients with HFpEF. Patients and methods: This study is a cross sectional descriptive study. In our study, we investigated 80 patients with unexplained exertional dyspnea with normal resting LV filling pressure at rest. Some of these patients may show elevated LV filling pressure with exercise. The current guidelines recommend to do diastolic stress echocardiography for those patients. All patients underwent complete resting echocardiography including assessment of diastolic dysfunction using the recommended 2016 guidelines and left ventricular mass index. Then we did diastolic stress echocardiography for all participants and the result of diastolic stress echocardiography was compared with the resting LVMI results.

Exercise-Induced Pulmonary Arterial Hypertension Causing Recurrent Unexplained Exertional Dyspnea: A Case Report

Exercise-Induced Pulmonary Arterial Hypertension Causing Recurrent Unexplained Exertional Dyspnea: A Case Report

Role of small airway dysfunction in unexplained exertional dyspnoea.

Isolated small airway abnormalities may be demonstrable at rest in patients with normal spirometry; however, the relationship of these abnormalities to exertional symptoms remains uncertain. This study uses an augmented cardiopulmonary exercise test (CPET) to include evaluation of small airway function during and following exercise to unmask abnormalities not evident with standard testing in individuals with dyspnoea and normal spirometry. Three groups of subjects were studied: 1) World Trade Center (WTC) dust exposure (n=20); 2) Clinical Referral (n=15); and Control (n=13). Baseline evaluation included respiratory oscillometry. Airway function during an incremental workload CPET was assessed by: 1) tidal flow versus volume curves during exercise to assess for dynamic hyperinflation and expiratory flow limitation; and 2) post-exercise spirometry and oscillometry to evaluate for airway hyperreactivity. All subjects demonstrated normal baseline forced expiratory volume in 1 s (FEV1)/forced vital capacity (FVC). Dyspnoea was reproduced during CPET in WTC and Clinical Referral groups versus Control without abnormality in respiratory pattern and minute ventilation. Tidal flow-volume curves uncovered expiratory flow limitation and/or dynamic hyperinflation with increased prevalence in WTC and Clinical Referral versus Control (55%, 87% versus 15%; p<0.001). Post-exercise oscillometry uncovered small airway hyperreactivity with increased prevalence in WTC and Clinical Referral versus Control (40%, 47% versus 0%, p<0.05). We uncovered mechanisms for exertional dyspnoea in subject with normal spirometry that was attributable to either small airway dysfunction during exercise and/or small airway hyperreactivity following exercise. The similarity of findings in WTC environmentally exposed and clinically referred cohorts suggests broad relevance for these evaluations.

728 GALECTINE-3 AND SST2 IN SYSTEMIC SCLEROSIS: AN EARLY DETECTION OF PULMONARY VASCULAR INVOLVEMENT IS REALLY POSSIBLE?

Abstract Introduction Pulmonary arterial hypertension (PAH) is a rare form of pulmonary hypertension (PH) that may also be associated with connective tissue diseases (CTD). In particular, PAH may affect from 5 to 19% of patients with systemic sclerosis (SSc), leading to a significant prognostic worsening. The current challenge is an early detection of PAH in such patients, in order to provide an early referral to PH centers to supply specific therapies as soon as possible. In the latest ESC guidelines for PH, cardiopulmonary exercise testing (CPET) has been included in the diagnostic algorithm for patients with unexplained exertional dyspnoea and/or suspected PH. Patients with PAH show a typical pattern, with a low end-tidal partial pressure of carbon dioxide (PETCO2), high ventilatory equivalent for carbon dioxide (VE/VCO2), low oxygen pulse (VO2/ HR) and low peak oxygen uptake (VO2). CPET may identify patients with SSc at low risk of PAH, to avoid unnecessary right heart catheterization (RHC). However, CPET is not available in all centers. So, we designed a preliminary study to identify new biomarkers that correlate with CPET's parameters. Material and Methods We enrolled 62 SSc patients [53 females, median age 52 years] with no other comorbidities and asymptomatic for dyspnea or other symptoms. 56% and 44% of them presented limited cutaneous SSc (lcSSc) and diffuse cutaneous SSc (dcSSc), respectively. For all patients we performed serum analysis for sST2, Galectine-3, pro-ANP, BNP and IL6, diagnostic imaging with echocardiography and cardiac MRI, CPET and pulmonary functionality test (PFT). Results All patients presented normal echocardiographic and RMI imaging findings. Galectin-3, sST2, pro-ANP, BNP and IL6 presented respectively the following median value: 13.45 ng/mL [11.78; 18.70], 23.25 ng/mL [13.04; 43.35], 1897 fmol/ml [1487; 2445], 12.18 pg/mL [9.34; 15.01]. Both Galectin-3 and sST2 showed a linear correlation with VE/VCO2 slope with R 0.339 (P-value 0.018) and 0.355 (P-value 0.013) respectively. After linear regression analysis, Galectin-3 and sST2 were overall statistically significant with R2 of 0.115 and 0.126, F of 5.97 and 6.62 and P-value of 0.018 and 0.013, respectively. It was found that Galectin-3 and SST2 significantly predicted VE/VCO2 slope with β = 0.364 [0,064; 0,665] for Galectin-3 and 0.137 [0,030; 0,244] for SST2. All other CPET parameters did not show correlation with the biomarkers. Conclusion Our preliminary results suggest that Galectine-3 and sST2 may be useful biomarkers for predicting increasing VE/VCO2 slope. Future analysis may confirm the role of these new biomarkers for early detection of pulmonary vascular involvement in SSc patients to allow an early referral and treatment and, conversely, to avoid unnecessary RHC.

Value of diastolic stress echocardiography combined with speckle tracking imaging in assessment of patients with exertional dyspnea and normal resting left ventricular functions

Abstract Background A group of patients presenting with exertional dyspnea and a preserved left ventricular ejection fraction (LVEF) have a normal resting left ventricular (LV) filling pressure which increases with exercise or stress due to diastolic dysfunction. Objectives We aimed to study the value of diastolic stress echocardiography combined with speckle tracking imaging in assessment of patients with exertional dyspnea and normal resting LV functions. Patients We prospectively studied 200 patients their age ≤60years who had unexplained exertional dyspnea and unable to do exercise test including those with (severe physical or mental inability, morbid obesity, recent stroke, etc) all patients included in the study had a normal both LV systolic function (LVEF≥50%), and diastolic function by conventional echocardiography. Methods All patients were subjected to a standard DSE protocol with incremental dobutamine infusion rates of 5, 10, 20, 30, and 40 mg/kg/min each stage lasts for 3 minutes, and the following LV echo parameters were recorded at baseline and at peak dose of the DSE; LVEF, (E/e') it is the ratio between early mitral inflow velocity and mitral annular early diastolic velocity, also two-dimensional speckle tracking imaging(2D-STI) was done to measure LV global longitudinal systolic strain (GLS), global longitudinal diastolic strain rate (DSr) during early filling (DSrE), late diastole (DSrA). Results The study included 200 patients their mean age 45.7 ± 8.4 years(60% were males). The LVEF, and the GLS showed non-significant difference at baseline compared to peak dose DSE (P=0.81, 0.73 respectively), the E/e', DSrA and E/DSrE were significantly increased from baseline to peak study(p &amp;lt;0.001, 0.003,and 0.006 respectively), while DSrE was significantly decreased at peak stress(p &amp;lt; 0.001), and the E/DSrE, and DSrE were significantly correlated to E/e'(p &amp;lt; 0.001) Conclusions DSE combined with global diastolic strain rate parameters are valuable methods to evaluate diastolic dysfunction in patients with exertional dyspnea and normal resting myocardial functions. Additional Content An author video to accompany this abstract is available on https://academic.oup.com/eurheartjsupp. Please click on the arrow next to ‘More Content’ and then click on ‘Author videos’.

Pulmonary hypertension in the elderly. Is it an overdiagnosis or a distinct entity?

The diagnosis of pulmonary hypertension (PH) in the elderly has become more common, recently. The possibility of overdiagnosis or misdiagnosis may arise in the elderly due to accompanying physiological changes and comorbidities. In this study, we aimed at revealing the clinical findings of individuals aged 60 years and older who were diagnosed with Group 1 and Group 4 PH, and at determining their differences with younger adults. Patients aged 60 years and older who were diagnosed with PH were identified. Among these patients, patients with a diagnosis of Group 1 PH (PAH) and Group 4 PH (CTEPH) were selected. A control group was formed from young and middle-aged patients. Demographic, clinical and hemadynamic characteristics of the elderly patients and the control group were analyzed. The mean WHO Functional Class and the Charlson Comorbidity Index score were significantly higher; the mean EF was significantly lower in the elderly. The right heart catheterization results were assessed. While the mean PAP was significantly higher in young-middle-aged patients (49.6 vs. 39.2 mmHg) (p=0.03), the mean PCWB was significantly higher in the elderly (11.4 vs. 8.1 mmHg) (p=0.005). The young-middle-aged patients had a significantly higher mean PVR values (10.7 vs. 8.3 WU) (p=0.01). Comorbidities and age-related functional losses may complicate the diagnosis of PH in elderly. Group 2 PH, which we frequently encounter in the elderly, may mask the true Group 1 or Group 4 PH in these patients. PH should be kept in mind in the elderly patients with unexplained exertional dyspnea.

Pulmonary hypertension during exercise underlies unexplained exertional dyspnoea in patients with Type 2 diabetes.

To compare the cardiac function and pulmonary vascular function during exercise between dyspnoeic and non-dyspnoeic patients with Type 2 diabetes mellitus (T2DM). Forty-seven T2DM patients with unexplained dyspnoea and 50 asymptomatic T2DM patients underwent exercise echocardiography combined with ergospirometry. Left ventricular (LV) function [stroke volume, cardiac output (CO), LV ejection fraction, systolic annular velocity (s')], estimated LV filling pressures (E/e'), mean pulmonary arterial pressures (mPAPs) and mPAP/COslope were assessed at rest, low- and high-intensity exercise with colloid contrast. Groups had similar patient characteristics, glycemic control, stroke volume, CO, LV ejection fraction, and E/e' (P > 0.05). The dyspnoeic group had significantly lower systolic LV reserve at peak exercise (s') (P = 0.021) with a significant interaction effect (P < 0.001). The dyspnoeic group also had significantly higher mPAP and mPAP/CO at rest and exercise (P < 0.001) with significant interaction for mPAP (P < 0.009) and insignificant for mPAP/CO (P = 0.385). There was no significant difference in mPAP/COslope between groups (P = 0.706). However, about 61% of dyspnoeic vs. 30% of non-dyspnoeic group had mPAP/COslope > 3 (P = 0.009). The mPAP/COslope negatively predicted V̇O2peak in dyspneic group (β = -1.86, 95% CI: -2.75, -0.98; multivariate model R2:0.54). Pulmonary hypertension and less LV systolic reserve detected by exercise echocardiography with colloid contrast underlie unexplained exertional dyspnoea and reduced exercise capacity in T2DM.

Diagnostic tests and subtypes of dysfunctional breathing in children with unexplained exertional dyspnea.

Inappropriate hyperventilation during exercise may be a specific subtype of dysfunctional breathing (DB). To assess whether Nijmegen questionnaire and hyperventilation provocation test (HVPT) are able to differentiate inappropriate hyperventilation from other DB subtypes in children with unexplained exertional dyspnea, and normal spirometry and echocardiography. The results were compared between a subgroup of 25 children with inappropriate hyperventilation (increased V'E/V'CO2 slope during a cardiopulmonary exercise test (CPET)) and an age and sex matched subgroup of 25 children with DB without hyperventilation (median age, 13.5 years; 36 girls). Anxiety was evaluated using State-Trait Anxiety Inventory for Children questionnaire. All children were normocapnic (at rest and peak exercise) and the children with hyperventilation had lower tidal volume/vital capacity on peak exercise (shallow breathing). The Nijmegen score correlated positively with dyspnea during the CPET and the HVPT (p = 0.001 and 0.010, respectively) and with anxiety score (p = 0.022). The proportion of children with a positive Nijmegen score (≥19) did not differ between hyperventilation (13/25) and no hyperventilation (14/25) groups (p = 0.777). Fractional end-tidal CO2 (FETCO2 ) at 5-min recovery of the HVPT was < 90% baseline in all children (25/25) of both subgroups. Likewise, there was no significant difference between the two subgroups for other indices of HVPT (FETCO2 at 3-min recovery and symptoms during the test). The validity of the Nijmegen questionnaire and the HVPT to discriminate specific subtypes of dysfunctional breathing, as well as the relevance of the inappropriate hyperventilation subtype itself may both be questioned.

P231 PULMONARY ARTERY WEDGE PRESSURE VS LEFT VENTRICULAR END–DIASTOLIC PRESSURE DURING EXERCISE IN PATIENTS WITH UNEXPLAINED DYSPNEA

Abstract Background Left ventricular end–diastolic pressure (LVEDP) approximates LV stiffness. Pulmonary artery wedge pressure (PAWP) reflects the hemodynamic load imposed by the left heart on the pulmonary circulation, with the interposition of the left atrium (LA). PAWP is frequently seen as a surrogate measure for LVEDP, but the two measures may not coincide. The imprecision of PAWP estimates for LVEDP and the disagreement between the two measures have been widely described for cardiac catheterization at rest. PAWP measurement during exercise has been advocated to discriminate heart failure with preserved ejection fraction (HFpEF) from non–cardiac dyspnea (NCD), with an end–expiratory pathologic threshold ≥25 mmHg. However, a formal comparison of PAWP vs LVEDP during exercise has never been performed. Aim. We sought to compare LVEDP and PAWP during exercise. Methods We retrospectively analyzed consecutive patients with unexplained dyspnea and a normal LV ejection fraction, who performed right and left heart catheterization at rest and during exercise. Results Forty–six consecutive patients were included in the analysis (80% with a peak PAWP ≥25 mmHg). We found a good correlation between both end–diastolic and mean PAWP on one side, and LVEDP on the other side (R2&amp;gt;0.55). End–expiratory, end–diastolic (mid–A) peak PAWP had no bias as compared with LVEDP, while mean PAWP slightly overestimated LVEDP by 1–2 mmHg. However, confidence intervals were quite large (Figure 1), suggesting imprecision of PAWP estimates for LVEDP. A disagreement between PAWP and LVEDP, using a threshold of ≥ 25 mmHg for both variables at peak exercise, was found in 11% of patients. In 4%, PAWP was ≥25 but LVEDP &amp;lt;25 mmHg, due to the appearance of tall V waves in the PAWP position (increased LA stiffness), increasing PAWP above LVEDP. In 7%, LVEDP was ≥25 but PAWP &amp;lt;25 mmHg. Those patients would have not been diagnosed as HFpEF based on peak PAWP alone. However, they had a PAWP increase during exercise relative to cardiac output changes (PAWP/CO slope) &amp;gt;2 mmHg/L/min, as an alternative parameter confirming HFpEF. Conclusions PAWP estimates for LVEDP during exercise bear a good correlation and a minimal bias, albeit being burdened by a relevant imprecision. In patients with unexplained exertional dyspnea and peak PAWP &amp;lt;25 mmHg, additional measures (including LVEDP or PAWP/CO slope) may be indicated in order to maximize the diagnostic yield of exercise cardiac catheterization.

Unexplained exercise-related dyspnea in type 2 diabetes predicts pulmonary arterial hypertension during exercise

Abstract Funding Acknowledgements Type of funding sources: None. Purpose To evaluate whether type 2 diabetes mellitus (T2DM) patients who suffer from unexplained exercise-induced dyspnea display cardiac dysfunction during exercise. Background Patients with type 2 diabetes mellitus (T2DM) frequently suffer from unexplained dyspnea. It is not fully understood whether these patients have a worse exercise capacity and cardiac dysfunction than non-dyspneic patients. If so, it would be clinically relevant to evaluate cardiac function in T2DM patients with unexplained dyspnea and initiate treatment accordingly. Methods 47 T2DM patients with unexplained dyspnea and 50 asymptomatic T2DM patients underwent echocardiography with simultaneous cardiopulmonary exercise testing (CPETecho). Left ventricular (LV) function (cardiac output, LV ejection fraction, stroke volume), estimated LV filling pressures (E/e’) and mean pulmonary artery pressures (mPAP) were assessed at rest, low- and high-intensity exercise by using colloid contrast. Breath-by-breath analyses were used to monitor exercise intensity and evaluate exercise capacity (V̇O2peak). Results The groups had similar characteristics and glycemic control (p&amp;gt;0.05). LV function and E/e’ were similar between groups during all stages of exercise (p&amp;gt;0.05). However, mPAP increased disproportionally (mPAP/CO &amp;gt; 3) during exercise in 62% of the patients with dyspnea. The mPAP/CO slope was significantly steeper in the patients with, as opposed to without dyspnea (Pinteraction=0.013). Moreover, a steeper mPAP/cardiac output slope (β= -1.86, 95% CI -2.75, -0.98) was an independent predictor of lower V̇O2peak (multivariate model R²:0.54). Conclusion In T2DM patients with unexplained exertional dyspnea, simultaneous cardiopulmonary exercise testing and echocardiography frequently reveal a reduced exercise capacity associated with exercise-induced pulmonary arterial hypertension. Dyspneic T2DM patients possibly have early left atrial and LV diastolic dysfunction. Timely preventive and therapeutic interventions may improve clinical outcomes in these patients.

Inflammatory Activation and Nitric Oxide Oxidation in Exertional Dyspnea in Southwest Asia Deployed Military Veterans

Post deployment personnel of the Southwest Asia theater of war present with significant exertional dyspnea. While deployed, these service men and women were exposed to a variety of inhaled toxicants including geological dust, burn pit smoke, and heavy metals. Upon examination, a large portion of these veterans display near‐normal pulmonary function and gas exchange in the lung, making diagnosis and treatment difficult. The aim of this study is to define the physiological and biochemical profiles of individuals with unexplained exertional dyspnea. We hypothesized that exposure to airborne toxicants has led to a chronic activated inflammatory state in the systemic vasculature, resulting in increased oxidative stress and reducing the bioavailability of nitric oxide (NO), contributing to the symptoms of dyspnea.Eligible veterans were tested for lung function by spirometry including diffusing capacity for carbon monoxide (DLco). Resting blood samples were taken and immediately separated into plasma and cellular components. Granuloyctes were removed from whole blood by magnetic separation, and subsequent leukocytes were collected and gated on expression of the myeloid marker CD45. Within CD45+ cells, flow cytometry was used to analyze the expression of inflammatory macrophage activation markers CD87, CD11b, CD163, HLA‐DR, CD195, CD192, CD14, CD16. Circulating levels of nitrite and nitrate (oxidation products of NO) were measured in plasma via reductive chemiluminescence, and the ratio of nitrate/nitrite (NOx ratio) was used as a marker for reduced bioavailability of NO. Increased expression of inflammatory marker CD87 in CD11b+ cells was positively correlated with expression of CD163 in HLA‐DR+ and CD14 in CD16+ (rho = .54, p &lt;.01; rho= .36, p= .047; n =30), but not CD195 in CD192+ (rho =‐.3, p =.1). Similar observations were observed in granulocytic cells regarding CD66b expression. This correlation between activation markers within the circulating myeloid‐derived cells is consistent with the presence of monocyte activation in the systemic vasculature. NOx levels were within normally observable bounds, however, the NOx ratio was negatively correlated with FEV1/FVC (a marker of lung obstruction) but not with %predicted DLco(rho =‐.56, p =.016; rho =.01, p = .96, n = 18). The reduction in FEV1/FVC with increased NOx ratio suggests potential loss of endothelial function, which may be contributing to exertional dyspnea and is currently under investigation.

Lower DLco% identifies exercise pulmonary hypertension in patients with parenchymal lung disease referred for dyspnea.

Exercise pulmonary hypertension is an underappreciated form of physical limitation related to early pulmonary vascular disease. A low diffusing capacity of lungs for carbon monoxide (DLco) can be seen in patients with resting pulmonary hypertension as well as parenchymal lung disease. It remains unclear whether low DLco% identifies early pulmonary vascular disease. We hypothesize that a reduced DLco% differentiates the presence of exercise pulmonary hypertension in patients with parenchymal lung disease. Fifty-six patients referred for unexplained exertional dyspnea with pulmonary function tests within six months of hemodynamic testing underwent exercise right heart catheterization. Exclusion criteria included resting pulmonary arterial or venous hypertension. Receiver operator characteristic curve determined the optimal DLco% cutoffs based on the presence or absence of parenchymal lung disease. Twenty-one (37%) patients had parenchymal lung disease, most common manifesting as chronic obstructive lung disease or interstitial lung disease. In patients with parenchymal lung disease, a DLco of 46% demonstrated 100% sensitivity and 73% specificity for detecting exercise pulmonary hypertension. In patients without parenchymal lung disease, a DLco of 73% demonstrated 58% sensitivity and 94% specificity for detecting exercise pulmonary hypertension. In both cohorts, DLco% below the optimum cutoffs were associated with higher peak mean pulmonary arterial pressure and peak total pulmonary resistance consistent with the hemodynamic definition of exercise pulmonary hypertension. Patients with a DLco < 46% were more often treated with pulmonary vasodilators and had a trend to higher mortality and lung transplant. DLco% is a simple non-invasive screening test for the presence of exercise pulmonary hypertension in our mixed referral population with progressive exertional dyspnea. DLco < 46% with parenchymal lung disease and DLco < 73% without parenchymal lung disease may play a role in differentiating the presence of pulmonary vascular disease prior to invasive hemodynamic testing.

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

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

A Simple, Evidence-Based Approach to Help Guide Diagnosis of Heart Failure With Preserved Ejection Fraction.

Diagnosis of heart failure with preserved ejection fraction (HFpEF) is challenging in euvolemic patients with dyspnea, and no evidence-based criteria are available. We sought to develop and then validate noninvasive diagnostic criteria that could be used to estimate the likelihood that HFpEF is present among patients with unexplained dyspnea to guide further testing. Consecutive patients with unexplained dyspnea referred for invasive hemodynamic exercise testing were retrospectively evaluated. Diagnosis of HFpEF (case) or noncardiac dyspnea (control) was ascertained by invasive hemodynamic exercise testing. Logistic regression was performed to evaluate the ability of clinical findings to discriminate cases from controls. A scoring system was developed and then validated in a separate test cohort. The derivation cohort included 414 consecutive patients (267 cases with HFpEF and 147 controls; HFpEF prevalence, 64%). The test cohort included 100 consecutive patients (61 with HFpEF; prevalence, 61%). Obesity, atrial fibrillation, age >60 years, treatment with ≥2 antihypertensives, echocardiographic E/e' ratio >9, and echocardiographic pulmonary artery systolic pressure >35 mm Hg were selected as the final set of predictive variables. A weighted score based on these 6 variables was used to create a composite score (H2FPEF score) ranging from 0 to 9. The odds of HFpEF doubled for each 1-unit score increase (odds ratio, 1.98; 95% CI, 1.74-2.30; P<0.0001), with an area under the curve of 0.841 ( P<0.0001). The H2FPEF score was superior to a currently used algorithm based on expert consensus (increase in area under the curve of 0.169; 95% CI, 0.120-0.217; P<0.0001). Performance in the independent test cohort was maintained (area under the curve, 0.886; P<0.0001). The H2FPEF score, which relies on simple clinical characteristics and echocardiography, enables discrimination of HFpEF from noncardiac causes of dyspnea and can assist in determination of the need for further diagnostic testing in the evaluation of patients with unexplained exertional dyspnea.

Cardiopulmonary Exercise Testing for Evaluating Patients with Unexplained Exertional Dyspnoea: Potential Role in Risk Stratification?

Cardiopulmonary Exercise Testing for Evaluating Patients with Unexplained Exertional Dyspnoea: Potential Role in Risk Stratification?

A case difficult to diagnose in adults: High sinus venous atrial septal defect

Sinus venous atrial septal defect (SVD) is highly difficult to diagnose because of its location. Below, we report a case of SVD which is misdiagnosed as pulmonary hypertension and anomalous pulmonary venous return. A 57-year-old female patient was referred to congenital disease outpatient clinic of a tertiary center. She was admitted to the hospital with complaints of fatigue and exercise dyspnea which had started a year ago. She had transthoracic echocardiography (TTE) examination done in another hospital which showed dilated right heart chambers and pulmonary hypertension. She underwent transesophageal echocardiography (TEE) examination with the suspicion of atrial septal defect (ASD), but no defect was seen. As her symptoms persisted, we repeated the TTE and TEE examination in our center. TEE revealed 0.6 cm ASD on the upper side of the interatrial septum. All four pulmonary veins were draining into the left atrium. Right heart catheterization (RHC) confirmed the diagnosis. A left-to-right shunt was detected and localized by a significant step-up in blood oxygen saturation found between mid and upper segments of the right atrium. According to our TEE and RHC results, we planned the surgical closure of the defect. Sinus venous ASD is deficiency of the superior portion of atrial septum adjacent to superior vena cava. Diagnosis of SVD is often more difficult than other forms of ASD and may require special imaging such as TEE, magnetic resonance imaging, or computed tomographic scanning. In conclusion, cardiologists must be aware about the possibility of SVD patients who have unexplained exertional dyspnea and fatigue, dilated right atrium and ventricle, pulmonary hypertension, paradoxical embolism, or atrial arrhythmias in their respective populations.

Multiple Pulmonary Arteriovenous Fistula in a Mother and His Son: A Case Report

Multiple Pulmonary Arteriovenous Fistulas (PAVFs) are rare vascular abnormalities in the general population, with a report on 15000 autopsies revealing only 3 cases of multiple PAVFs. However, these abnormal communications between pulmonary arteries and veins are commonly seen in patients with Hereditary Hemorrhagic Telangiectasia (HHT). Several conditions such as cirrhosis, chest trauma, metastatic carcinoma, schistosomiasis, and systemic amyloidosis are accountable for acquired form PAVF. We describe 2 patients (mother and son) with multiple PAVFs and no apparent signs or symptoms suggestive of HHT. A pulmonary artery injection wes performed for Case 1 (mother) and showed bilateral PAVFs with aneurysmal dilation. Given the diagnosis of PAVFs in the mother, we considered the same pathology for the child’s symptoms. Therefore, the boy also underwent pulmonary angiography, which revealed multiple bilateral PAVFs. Both patients underwent interventional angiography and the PAVFs were occulted with stainless coil. In conclusion, the presence of multiple PAVFs should be considered in the differential diagnosis of patients with unexplained exertional dyspnea and cyanosis, even in the absence of diagnostic features suggestive of HHT.

Contemporary diagnosis and management of pulmonary hypertension

Pulmonary hypertension (PH) encompasses a group of diseases associated with an elevated mean pulmonary artery pressure (mPAP) ≥25 mm Hg at rest. The symptoms of PH are non-specific, and it...