Echocardiographic assessment of pulmonary capillary wedge pressure in patients with frequent premature ventricular complexes.

BACKGROUND: Premature ventricular complex (PVC) is seen in most individuals. It has been shown that the kinetics-tracking index or Kawasaki-Tanaka index (KT index) strongly predicts pulmonary capillary wedge pressure (PCWP) by noninvasively. KT index was defined as log10 (active LAEF/minimum LAV index). We goaled to assess PCWP non-invasively in patients with frequent PVCs with normal left ventricular systolic functions and to evaluate whether there is an increase in PCWP before systolic and diastolic functions are impaired. METHODS: About 55 patients with frequent PVCs as a patient group and 54 healthy volunteers as a control group were involved to the study. After the conventional echocardiographic examination, the vendor-independent software system (EchoPAC version 202) was used to obtain the time-left atrial volume (LAV) curve. total left atrial emptying function (LAEF), passive LAEF, and active LAEF were calculated to evaluate phasic left atrial (LA) function. In this study, ePCWP was calculated using the KT index, and KT index results and other echocardiographic parameters were compared between study groups. RESULTS: LA anterior-posterior dimension, LA maximum volume index, and LA minimum volume index were significantly larger in the patient group (all p values < .001). Total LAEF were significantly reduced in patients with frequent PVC (p < .001). Estimated pulmonary capillary wedge pressure (ePCWP) by KT index was significantly higher in patients with frequent PVCs (p < .001). CONCLUSIONS: Patients with frequent PVC had increased ePCWP as assessed by KT index.

Echocardiographic assessment of pulmonary capillary wedge pressure by E/e' ratio: A systematic review and meta-analysis.

BACKGROUND: The reliability of echocardiographic methods for the assessment of pulmonary capillary wedge pressure (PCWP) is still a matter of debate. Since its first description, the E/e' ratio has been regarded as a suitable method. The aim of this study is to evaluate the evidence of how E/e' effectively estimates PCWP and its diagnostic accuracy for elevated PCWP. METHODS: We systematically searched MEDLINE and Embase databases for studies investigating the agreement between E/e' and PCWP, from inception to July 2022. We limited our research to studies published from 2010 to date. Retrospective studies and studies on non-adult population were excluded. RESULTS: Twenty-eight studies, involving a total of 1964 subjects, were included. The pooled analysis of the studies showed a modest correlation between E/e' and PCWP. The weighted average correlation (r) is 0.43 (95% CI 0.37-0.48). We found no significant differences between reduced and preserved ejection fraction groups. Thirteen studies analysed the diagnostic accuracy of E/e' for elevated PCWP. The AUC of receiver operating characteristic curves for PCWP >15 mmHg was estimated in the interval 0.6-0.91. DISCUSSION: E/e' appears to have a modest correlation with PCWP and an acceptable accuracy for elevated PCWP. (PROSPERO number, CRD42022333462).

Surgical Repair of Truncus Arteriosus: A Long-Term Hemodynamic Assessment.

Background: Unrepaired truncus arteriosus (TA) carries poor prognosis due to complications of unrestricted pulmonary flow, truncal valve insufficiency, and pulmonary vascular disease. Currently, the hemodynamic profile of adults late after TA repair is unknown. We reviewed the hemodynamics, prevalence, and pathophysiology of pulmonary hypertension (PH) in this population. Methods: Eighteen adult patients with repaired TA who underwent cardiac catheterization at Mayo Clinic, MN, between 1997 and 2021 were identified. PH was defined as either precapillary (mean pulmonary artery pressure [mPAP] ≥25 mm Hg, pulmonary artery wedge pressure [PAWP] ≤15 mm Hg, and pulmonary vascular resistance [PVR] >3 Wood units), isolated postcapillary (mPAP ≥25, PAWP >15, PVR ≤3), or combined (mPAP ≥25, PAWP >15, and PVR >3). Diastolic pressure and transpulmonary gradients were used as ancillary data for classification. Results: Mean age at catheterization was 34 ± 10 years. Mean right ventricular (RV) systolic pressure was 82 ± 22.6 mm Hg, mean right and left mPAPs 28.1 ± 16.2 and 27.9 ± 11.9 mm Hg, respectively. Seven patients (41.2%) had PAWP >15 mm Hg and, among those undergoing arterial catheterization, 7 (53.8%) had a left ventricular (LV) end-diastolic pressure >15 mm Hg. PH was diagnosed in 13 patients (72.2%): 6 (33.3%) precapillary, 4 (22.2%) isolated postcapillary, and 3 (16.7%) combined. PAWP >15 mm Hg was associated with male sex (P = .049),

Ratio of Mixed Venous Oxygen Saturation-to-Pulmonary Capillary Wedge Pressure: Insights From the Veterans Affairs Clinical Assessment, Reporting, and Tracking Program.

BACKGROUND: Hemodynamic values from right heart catheterization aid diagnosis and clinical decision-making but may not predict outcomes. Mixed venous oxygen saturation percentage and pulmonary capillary wedge pressure relate to cardiac output and congestion, respectively. We theorized that a novel, simple ratio of these measurements could estimate cardiovascular prognosis. METHODS: We queried Veterans Affairs' databases for clinical, hemodynamic, and outcome data. Using the index right heart catheterization between 2010 and 2016, we calculated the ratio of mixed venous oxygen saturation-to-pulmonary capillary wedge pressure, termed ratio of saturation-to-wedge (RSW). The primary outcome was time to all-cause mortality; secondary outcome was 1-year urgent heart failure presentation. Patients were stratified into quartiles of RSW, Fick cardiac index (CI), thermodilution CI, and pulmonary capillary wedge pressure alone. Kaplan-Meier curves and Cox proportional hazards models related comparators with outcomes. RESULTS: Of 12 019 patients meeting inclusion criteria, 9826 had values to calculate RSW (median 4.00, interquartile range, 2.67-6.05). Kaplan-Meier curves showed early, sustained separation by RSW strata. Cox modeling estimated that increasing RSW by 50% decreases mortality hazard by 19% (estimated hazard ratio, 0.81 [95% CI, 0.79-0.83], P<0.001) and secondary outcome hazard by 28% (hazard ratio, 0.72 [95% CI, 0.70-0.74], P<0.001). Among the 3793 patients with data for all comparators, Cox models showed RSW best associated with outcomes (by both C statistics and Bayes factors). Furthermore, pulmonary capillary wedge pressure was superior to thermodilution CI and Fick CI. Multivariable adjustment attenuated without eliminating the association of RSW with outcomes. CONCLUSIONS: In a large national database, RSW was superior to conventional right heart catheterization indices at assessing risk of mortality and urgent heart failure presentation. This simple calculation with routine data may contribute to clinical decision-making in this population.

External assessment of the EUROMACS right-sided heart failure risk score.

The EUROMACS Right-Sided Heart Failure Risk Score was developed to predict right ventricular failure (RVF) after left ventricular assist device (LVAD) placement. The predictive ability of the EUROMACS score has not been tested in other cohorts. We performed a single center analysis of a continuous-flow (CF) LVAD cohort (n = 254) where we calculated EUROMACS risk scores and assessed for right ventricular heart failure after LVAD implantation. Thirty-nine percent of patients (100/254) had post-operative RVF, of which 9% (23/254) required prolonged inotropic support and 5% (12/254) required RVAD placement. For patients who developed RVF after LVAD implantation, there was a 45% increase in the hazards of death on LVAD support (HR 1.45, 95% CI 0.98-2.2, p = 0.066). Two variables in the EUROMACS score (Hemoglobin and Right Atrial Pressure to Pulmonary Capillary Wedge Pressure ratio) were not predictive of RVF in our cohort. Overall, the EUROMACS score had poor external discrimination in our cohort with area under the curve of 58% (95% CI 52-66%). Further work is necessary to enhance our ability to predict RVF after LVAD implantation.

Risk assessment in severe pulmonary hypertension due to interstitial lung disease.

BACKGROUND: The updated hemodynamic definition of pulmonary hypertension (PH) due to interstitial lung disease (ILD) differentiates severe and non-severe phenotypes, but no further risk stratification strategy has been established or validated for severe PH due to ILD. We aimed to assess the prognostic value of a truncated version of the European Society of Cardiology/European Respiratory Society (ESC/ERS) PH risk stratification scheme in severe PH due to ILD. METHODS: We retrospectively analyzed 185 patients with severe PH (mean pulmonary artery pressure of ≥35 mm Hg or ≥25 mm Hg with cardiac index <2.0 liter/min/m2) due to ILD who were enrolled in the Giessen PH Registry after being referred for invasive diagnostic work-up of suspected PH during 1995‒2018. A truncated ESC/ERS risk stratification scheme (based on 8 parameters from the full scheme) was applied. Kaplan-Meier and univariate Cox regression analyses were used to evaluate transplant-free survival and hazard ratios, respectively. RESULTS: During follow-up (median [interquartile range]: 19 [7-40] months), 146 events occurred. Using baseline data for risk stratification, 5-year transplant-free survival of low-, intermediate-, and high-risk groups was 43%, 15%, and 4%, respectively (log-rank p = 0.010; hazard ratio of high- vs low-risk group: 3.116 [95% CI: 1.428-6.800]). Using follow-up data (at 11 [6.0-32.5] months) for risk stratification, 5-year survival of low-, intermediate-, and high-risk groups was 22%, 3%, and 0%, respectively (log-rank p = 0.005). CONCLUSIONS: The truncated ESC/ERS scheme was clinically useful and demonstrated prognostic relevance in severe PH due to ILD.

Risk assessment in pulmonary arterial hypertension: Insights from the GRIPHON study.

BACKGROUND: Approaches to risk assessment in pulmonary arterial hypertension (PAH) include the noninvasive French risk assessment approach (number of low-risk criteria based on the European Society of Cardiology and European Respiratory Society guidelines) and Registry to Evaluate Early and Long-term PAH Disease Management (REVEAL) 2.0 risk calculator. The prognostic and predictive value of these methods for morbidity/mortality was evaluated in the predominantly prevalent population of GRIPHON, the largest randomized controlled trial in PAH. METHODS: GRIPHON randomized 1,156 patients with PAH to selexipag or placebo. Post-hoc analyses were performed on the primary composite end-point of morbidity/mortality by the number of low-risk criteria (World Health Organization functional class I-II; 6-minute walk distance >440 m; N-terminal pro-brain natriuretic peptide <300 ng/liter) and REVEAL 2.0 risk category. Hazard ratios and 95% confidence intervals were calculated using Cox proportional hazard models. RESULTS: Both the number of low-risk criteria and the REVEAL 2.0 risk category were prognostic for morbidity/mortality at baseline and any time-point during the study. Patients with 3 low-risk criteria at baseline had a 94% reduced risk of morbidity/mortality compared to patients with 0 low-risk criteria and were all categorized as low-risk by REVEAL 2.0. The treatment effect of selexipag on morbidity/mortality was consistent irrespective of the number of low-risk criteria or the REVEAL 2.0 risk category at any time-point during the study. Selexipag-treated patients were more likely to increase their number of low-risk criteria from baseline to week 26 than placebo-treated patients (odds ratio 1.69, p = 0.0002); similar results were observed for REVEAL 2.0 risk score. CONCLUSIONS: These results support the association between risk profile and long-term outcome and suggest that selexipag treatment may improve risk profile.

Risk classification of pulmonary arterial hypertension by echocardiographic combined assessment of pulmonary vascular resistance and right ventricular function.

Which combination of clinical parameters improves the prediction of prognosis in patients with pulmonary arterial hypertension (PAH) remains unclear. We examined whether combined assessment of pulmonary vascular resistance and right ventricular function by echocardiography is useful for classifying risks in PAH. In 41 consecutive patients with PAH (mean age of 48.9 ± 17.3 years, 31 females), a 6-min walk test, pulmonary function test, and echocardiography were performed at baseline and during PAH-specific therapies. The study endpoint was defined as a composite of cardiovascular death and hospitalization for PAH and/or right ventricular failure. During a follow-up period of 9.2 ± 8.7 months, 18 patients reached the endpoint. Multivariate regression analysis showed that the ratio of tricuspid regurgitation pressure gradient to the time-velocity integral of the right ventricular outflow tract (TRPG/TVI) and tricuspid annular plane systolic excursion (TAPSE) during PAH-specific treatment were independent prognostic predictors of the endpoint. Using cutoff values indicated by receiver operating characteristic analysis, the patients were divided into four subsets. Multivariate analyses by Cox's proportional hazards model adjusted for age, sex and body mass index indicated that subset 4 (TRPG/TVI ≥ 3.89 and TAPSE ≤ 18.9 mm) had a significantly higher event risk than did subset 1 (TRPG/TVI < 3.89 and TAPSE > 18.9 mm): HR = 25.49, 95% CI 4.70-476.97, p < 0.0001. Combined assessment of TRPG/TVI and TAPSE during adequate PAH-specific therapies enables classification of risks for death and/or progressive right heart failure in PAH.

Intraoperative assessment of left-ventricular diastolic function by two-dimensional speckle tracking echocardiography: relationship between pulmonary capillary wedge pressure and peak longitudinal strain rate during isovolumetric relaxation in patients undergoing coronary artery bypass graft surgery.

OBJECTIVES: Two-dimensional speckle tracking echocardiography has advantages over tissue Doppler imaging during isovolumetric relaxation for predicting left-ventricular end-diastolic pressure in non-surgical patients. Considering the direct and indirect effects of general anesthesia on hemodynamics, we examined correlations between strain-based indices during isovolumetric relaxation and pulmonary capillary wedge pressure in anesthetized patients. Moreover, we determined applicable cut-off values for strain-based indices to predict pulmonary capillary wedge pressure ≥15 mmHg intraoperatively. DESIGN: Retrospective clinical study. SETTING: Single university hospital. PARTICIPANTS: Thirty adult patients with preserved ejection fraction undergoing coronary artery bypass grafting. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Two-dimensional speckle tracking echocardiography was used to measure strain rate during isovolumetric relaxation (SRIVR) and to calculate the mitral early diastolic inflow (E) to SRIVR ratio (E/SRIVR). Tissue Doppler imaging was used to calculate the E to early diastolic velocity at the lateral mitral annulus ratio (lateral E/e'). SRIVR and E/SRIVR showed strong correlations with pulmonary capillary wedge pressure (r = 0.80 and 0.73, respectively; p < 0.001 and p < 0.001). Lateral E/e' correlated with pulmonary capillary wedge pressure (r = 0.42; p < 0.05). SRIVR predicted high pulmonary capillary wedge pressure better than lateral E/e' did (areas under the receiver operating characteristic curves, 0.94-vs. 0.47, respectively). SRIVR <0.2 s-1 had a sensitivity of 100% and a specificity of 81% for predicting pulmonary capillary wedge pressure ≥15 mmHg. CONCLUSIONS: SRIVR is superior to tissue Doppler indices for predicting pulmonary capillary wedge pressure intraoperatively in patients with coronary artery disease and preserved ejection fraction.

Assessment of lung edema during ex-vivo lung perfusion by single transpulmonary thermodilution: A preliminary study in humans.

BACKGROUND: Single transpulmonary thermodilution (SD) with extravascular lung water index (EVLWI) could become a new tool to better assess lung graft edema during ex-vivo lung perfusion (EVLP). In this study we compare EVLWI with conventional methods to better select lungs during EVLP and to predict post-transplant primary graft dysfunction (PGD). METHODS: We measured EVLWI, arterial oxygen/fraction of inspired oxygen (P/F) ratio, and static lung compliance (SLC) during EVLP in an observational study. At the end of EVLP, grafts were accepted or rejected according to a standardized protocol blinded to EVLWI results. We compared the respective ability of EVLWI, P/F, and SLC to predict PGD. Mann-Whitney U-test, Fisher's exact test, and receiver-operating characteristic (ROC) curve data were used for analysis. p < 0.05 was considered statistically significant. RESULTS: Thirty-five lungs were evaluated by SD during EVLP. Three lungs were rejected for pulmonary edema. Thirty-two patients were transplanted, 8 patients developed Grade 2 or 3 PGD, and 24 patients developed Grade 0 or 1 PGD. In contrast to P/F ratio, SLC, and pulmonary artery pressure, EVLWI differed between these 2 populations (p < 0.001). The area under the ROC for EVLWI assessing Grade 2 or 3 PGD at the end of EVLP was 0.93. Donor lungs with EVLWI >7.5 ml/kg were more likely associated with a higher incidence of Grade 2 or 3 PGD at Day 3. CONCLUSIONS: Increased EVLWI during EVLP was associated with PGD in recipients.

Relationship Between Noninvasive Assessment of Lung Fluid Volume and Invasively Measured Cardiac Hemodynamics.

Background Right heart catheterization is the gold standard in clinical practice for the assessment of cardiovascular hemodynamics, but it is an invasive procedure requiring expertise in both insertion and reading. Remote dielectric sensing (Re DS ) is a noninvasive electromagnetic-based technology intended to quantify lung fluid content. Methods and Results In this prospective single-center study, Re DS readings were obtained in supine position just before right heart catheterization procedure in patients with heart failure. Agreement between Re DS and pulmonary artery wedge pressure ( PAWP ) was analyzed. Of all, 139 patients with heart failure received hemodynamic assessment and Re DS measurement. A good correlation was found between Re DS and PAWP measurement ( r=0.492, P<0.001). Receiver operating characteristic analysis of the ability to identify a PAWP ≥18 mm Hg resulted in a Re DS cutoff value of 34%, with an area under the curve of 0.848, a sensitivity of 90.7%, and a specificity of 77.1%. Overall, Re DS <34% carries a high negative predictive value of 94.9%. Conclusions Lung fluid content, as measured by Re DS , correlates well with PAWP . The high sensitivity and specificity and especially the high negative predictive value make Re DS a reliable noninvasive tool at the point of care, to rule out elevated PAWP in patients with heart failure and to help with medical management of patients with heart failure. Further studies are warranted to compare this tool with existing tests and to relate the findings to the clinical outcomes.

Novel Noninvasive Assessment of Pulmonary Arterial Stiffness Using Velocity Transfer Function.

Background Pulmonary artery ( PA ) stiffness is associated with increased pulmonary vascular resistance ( PVR ). PA stiffness is accurately described by invasive PA impedance because it considers pulsatile blood flow through elastic PA s. We hypothesized that PA stiffness and impedance could be evaluated noninvasively by PA velocity transfer function ( VTF ), calculated as a ratio of the frequency spectra of output/input mean velocity profiles in PA s. Methods and Results In 20 participants (55±19 years, 14 women) undergoing clinically indicated right-sided heart catheterization, comprehensive phase-contrast and cine-cardiac magnetic resonance imaging was performed to calculate PA VTF , along with right ventricular mass and function. PA impedance was measured as a ratio of frequency spectra of invasive PA pressure and echocardiographically derived PA flow waveforms. Mean PA pressure was 29.5±13.6 mm Hg, and PVR was 3.5±2.8 Wood units. A mixed-effects model showed VTF was significantly associated with PA impedance independent of elevation in pulmonary capillary wedge pressure ( P=0.005). The mean of higher frequency moduli of VTF correlated with PVR (ρ=0.63; P=0.003) and discriminated subjects with low (n=10) versus elevated PVR (≥2.5 Wood units, n=10), with an area under the curve of 0.95, similar to discrimination by impedance (area under the curve=0.93). VTF had a strong inverse association with right ventricular ejection fraction (ρ=-0.73; P<0.001) and a significant positive correlation with right ventricular mass index (ρ=0.51; P=0.02). Conclusions VTF , a novel right ventricular- PA axis coupling parameter, is a surrogate for PA impedance with the potential to assess PA stiffness and elevation in PVR noninvasively and reliably using cardiac magnetic resonance imaging.

Usefulness of scoring right ventricular function for assessment of prognostic factors in patients with chronic thromboembolic pulmonary hypertension.

Right ventricular (RV) function is associated with prognosis in chronic thromboembolic pulmonary hypertension (CTEPH). This study aimed to establish an RV dysfunction score using RV echocardiographic parameters to clarify the clinical characteristics in patients with CTEPH and to compare RV dysfunction score with parameters such as World Health Organization (WHO) functional class, hemodynamics, exercise capacity, and plasma BNP level. We enrolled 35 inpatients with CTEPH (mean age, 62 ± 15 years, 15 males). We constructed 'an RV dysfunction score' calculated as the summation of each point awarded for the presence of four parameters: tricuspid annular plane systolic excursion (TAPSE) < 16 mm, 1 point; tissue Doppler-derived tricuspid lateral annular systolic velocity (S') < 10 cm/s, 1 point; right ventricular fractional area change (RVFAC) < 35%, 1 point; and right ventricular myocardial performance index (RV-MPI) > 0.4, 1 point. TAPSE, S', RVFAC, and RV-MPI was 18.7 ± 4.8 mm, 11.9 ± 3.1 cm/s, 33.5 ± 13.9%, and 0.39 ± 0.2, respectively. The RV dysfunction score was associated with symptom [WHO functional class (p = 0.026)], hemodynamics [mean PAP (p = 0.01), cardiac index (p = 0.009), pulmonary vascular resistance (p = 0.001), and SvO2 (p = 0.039)], exercise capacity [6-min walk distance (p = 0.046), peakVO2 (p = 0.016), and VE/VCO2 slope (p = 0.031)], and plasma BNP level (p = 0.005). This RV dysfunction score using the four RV echocardiographic parameters could be a simple and useful scoring system to evaluate prognostic factors in patients with CTEPH.

Improving the echocardiographic assessment of pulmonary pressure using the tricuspid regurgitant signal-The "chin" vs the "beard".

AIM: Transthoracic echocardiography (TTE) is a fundamental investigation for the noninvasive assessment of pulmonary hemodynamics and right heart function. The aim of this study was to assess the correlation and agreement of Doppler calculation of right ventricular systolic pressure (RVSP) and pulmonary vascular resistance (PVR) using "chin" and "beard" measurements of tricuspid regurgitant velocity (TRVmax ), with invasive pulmonary artery systolic pressure (PASP) and PVR. METHODS: One hundred patients undergoing right heart catheterisation (RHC) and near simultaneous transthoracic echocardiography were studied. TRVmax was recorded for "chin" measurement (distinct peak TRVmax signal) and where available (63 patients), "beard" measurement (higher indistinct peak TRVmax signal). RESULTS: Measurable TRV signal was obtained in 96 patients. Mean RVSPchin 54.7 ± 22.7 mm Hg and RVSPbeard 68.6 = 23 ± 26.3 mm Hg (P < .001). There was strong correlation between both RVSPchin and RVSPbeard with invasive PASP (Pearson's r = .9, R2  = 0.82, P < .001 - r = .88, R = .78, P < .001, respectively.). Bland-Altman analysis for RVSPchin and RVSPbeard showed a mean bias of -0.5 mm Hg (95% limits of agreement -21.4 to 20.5 mm Hg) and -10.7 (95% LOA -35.5 to 14.2 mm Hg), respectively. Receiver operator characteristics of TRVmax "chin" and "beard" for diagnosis of pulmonary hypertension was assessed with optimal cut-offs being 2.8 m/s (sensitivity 93%, specificity 87%) and 3.2 m/s (sensitivity 91%, specificity 82%), respectively. There was similar correlation between PVRchin and PVRbeard (r = .87, R2  = 0.75, P < .001 and r = .86, R2  = 0.74, P < .001, respectively). At higher PVR, there was overestimation of calculated PVR using PVRbeard . CONCLUSION: The accuracy of noninvasive measurement of right heart pressures is increased using the "chin" in estimation of both RVSP and PVR.

Pulmonary Vascular Disease: Hemodynamic Assessment and Treatment Selection-Focus on Group II Pulmonary Hypertension.

PURPOSE OF REVIEW: Pulmonary hypertension due to left heart disease (PH-LHD) is the most common cause of pulmonary hypertension worldwide, yet therapies used to treat pulmonary arterial hypertension have failed to show efficacy in this population. Proper hemodynamic assessment and differentiation of pulmonary hypertension phenotypes is therefore critical for both current clinical practice and future research and therapeutic efforts. RECENT FINDINGS: Substantial recent efforts have sought to improve the hemodynamic characterization of pulmonary hypertension for both diagnostic and prognostic purposes. These efforts include identifying occult LHD using provocative maneuvers as well as sub-classifying PH-LHD based on the presence or absence of a pre-capillary component. How to best define the pre-capillary component remains controversial as several studies have drawn conflicting conclusions. The lack of standardization of hemodynamic measurements as well as measurement fidelity concerns may explain some of the discrepant results. Non-hemodynamic methods of PH-LHD classification may also have an emerging role. Despite recent advances, therapeutic studies have largely remained disappointing. In this review, we discuss the nuances and controversies surrounding diagnostic and prognostic hemodynamic characterization of PH-LHD as well as summarize the recent therapeutic efforts and ongoing challenges in this population.

Prognostic Effect and Longitudinal Hemodynamic Assessment of Borderline Pulmonary Hypertension.

Importance: Pulmonary hypertension (PH) is diagnosed by a mean pulmonary arterial pressure (mPAP) value of at least 25 mm Hg during right heart catheterization (RHC). While several studies have demonstrated increased mortality in patients with mPAP less than that threshold, little is known about the natural history of borderline PH. Objective: To test the hypothesis that patients with borderline PH have decreased survival compared with patients with lower mPAP and frequently develop overt PH and to identify clinical correlates of borderline PH. Design, Setting, and Participants: Retrospective cohort study from 1998 to 2014 at Vanderbilt University Medical Center, comprising all patients undergoing routine RHC for clinical indication. We extracted demographics, clinical data, invasive hemodynamics, echocardiography, and vital status for all patients. Patients with mPAP values of 18 mm Hg or less, 19 to 24 mm Hg, and at least 25 mm Hg were classified as reference, borderline PH, and PH, respectively. Exposures: Mean pulmonary arterial pressure. Main Outcome and Measures: Our primary outcome was all-cause mortality after adjusting for clinically relevant covariates in a Cox proportional hazards model. Our secondary outcome was the diagnosis of overt PH in patients initially diagnosed with borderline PH. Both outcomes were determined prior to data analysis. Results: We identified 4343 patients (mean [SD] age, 59 [15] years, 51% women, and 86% white) among whom the prevalence of PH and borderline PH was 62% and 18%, respectively. Advanced age, features of the metabolic syndrome, and chronic heart and lung disease were independently associated with a higher likelihood of borderline PH compared with reference patients in a logistic regression model. After adjusting for 34 covariates in a Cox proportional hazards model, borderline PH was associated with increased mortality compared with reference patients (hazard ratio, 1.31; 95% CI, 1.04-1.65; P = .001). The hazard of death increased incrementally with higher mPAP, without an observed threshold. In the 70 patients with borderline PH who underwent a repeated RHC, 43 (61%) had developed overt PH, with a median increase in mPAP of 5 mm Hg (interquartile range, -1 to 11 mm Hg; P < .001). Conclusions and Relevance: Borderline PH is common in patients undergoing RHC and is associated with significant comorbidities, progression to overt PH, and decreased survival. Small increases in mPAP, even at values currently considered normal, are independently associated with increased mortality. Prospective studies are warranted to determine whether early intervention or closer monitoring improves clinical outcomes in these patients.