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Introduction: Fluid challenge during right heart catheterization (RHC) identifies occult left heart diastolic dysfunction (Occ-DD) in 10-20% of patients initially diagnosed with pre-capillary pulmonary hypertension (PH). The prognostic implications of the response to fluid challenge are not known. Abnormal right ventricular (RV) function is a poor prognostic indicator in all forms of PH. Hypothesis: We hypothesized that fluid challenge during RHC identifies patients with worse RV function and survival. Methods: Consecutive patients referred for RHC with fluid challenge from 2009-2016 were studied. Occ-DD was defined by a resting pulmonary arterial wedge pressure (PAWP) < 15 mmHg, and a PAWP > 18 mmHg after 500cc fluid challenge. Resting DD was defined by resting PAWP > 15 mmHg. RV function was assessed by pulmonary artery pulsatility index (PAPi) or RV stroke work index (RVSWI). Statistical analysis was conducted using Kruskal Wallis test. Survival analysis was conducted by log rank test. Results: Of the 310 patients identified, 83% were female with a mean age of 54 + 14 years. The cohort consisted of 204 (66%) patients without DD, 30 (10%) with Occ-DD, and 76 (24%) with resting DD. Patients with Occ-DD were older (59 + 12 vs 51 + 14, p < 0.0001) with greater BMI (31 + 6 vs 28 + 7, p < 0.0001), but had similar prevalence of obesity, hypertension, diabetes mellitus, and coronary disease to all groups. Patients with Occ-DD had lower PAPi (7.8 + 0.4 vs 8.5 + 0.4, p < 0.0001), lower RVSWI (9.9 + 0.8 vs 17.8 + 0.7 mmHg*ml/m2, p < 0.0001) (Figure), and decreased survival (3.7 + 3.5 vs 4.9 + 3.5 years, p < 0.0001) compared to those without DD. After adjustment for RV function, survival was no longer different between groups. Conclusions: Patients with Occ-DD after fluid challenge during RHC have decreased survival due to worse RV function compared to patients without DD. These findings suggest important prognostic implications for fluid challenge in the evaluation of patients with PH.

Background There is an unclear relationship of obesity to the pathogenesis and severity of pulmonary arterial hypertension (PAH) and pulmonary venous hypertension (PVH). Research Question Is BMI casually associated with pulmonary artery pressure (PAP) and/or markers of pulmonary vascular remodeling? Study Design and Methods The study design was a two-sample inverse-variance weighted Mendelian randomization. We constructed two BMI genetic risk scores from genome-wide association study summary data and deployed them in nonoverlapping cohorts of subjects referred for right heart catheterization (RHC) or echocardiography. A BMI highly polygenic risk score (hpGRS) optimally powered to detect shared genetic architecture of obesity with other traits was tested for association with RHC parameters including markers of pulmonary vascular remodeling. A BMI strict genetic risk score (sGRS) composed of high-confidence genetic variants was used for Mendelian randomization analyses to assess if higher BMI causes higher PAP. Results Among all subjects, both directly measured BMI and hpGRS were positively associated with pulmonary arterial pressures but not markers of pulmonary vascular remodeling. Categorical analyses revealed BMI and hpGRS were associated with PVH but not PAH. Mendelian randomization of the sGRS supported that higher BMI is causal of higher systolic pulmonary artery pressure (sPAP). Sensitivity analyses showed sPAP-BMI sGRS relationship was preserved when either individuals with PAH or PVH were excluded. In the echocardiographic cohort, BMI and hpGRS were positively associated with estimated PAP and markers of left heart remodeling. Interpretation BMI is a modifier of pulmonary hypertension severity in both PAH and PVH but is only involved in the pathogenesis of PVH.

Pulmonary arterial hypertension (PAH) is a rare disease that leads to premature death from right heart failure. It is strongly associated with elevated red cell distribution width (RDW), a correlate of several iron status biomarkers. High RDW values can signal early-stage iron deficiency or iron deficiency anaemia. This study investigated whether elevated RDW is causally associated with PAH. A two-sample Mendelian randomisation (MR) approach was applied to investigate whether genetic predisposition to higher levels of RDW increases the odds of developing PAH. Primary and secondary MR analyses were performed using all available genome-wide significant RDW variants (n=179) and five genome-wide significant RDW variants that act via systemic iron status, respectively. We confirmed the observed association between RDW and PAH (OR 1.90, 95% CI 1.80–2.01) in a multicentre case–control study (cases n=642, disease controls n=15 889). The primary MR analysis was adequately powered to detect a causal effect (odds ratio) between 1.25 and 1.52 or greater based on estimates reported in the RDW genome-wide association study or from our own data. There was no evidence for a causal association between RDW and PAH in either the primary (ORcausal 1.07, 95% CI 0.92–1.24) or the secondary (ORcausal 1.09, 95% CI 0.77–1.54) MR analysis. The results suggest that at least some of the observed association of RDW with PAH is secondary to disease progression. Results of iron therapeutic trials in PAH should be interpreted with caution, as any improvements observed may not be mechanistically linked to the development of PAH., Mendelian randomisation using genetic data from the largest-to-date PAH cohort does not support red cell distribution width or iron deficiency as a cause of PAH, which is important when interpreting iron replacement trials in this condition http://bit.ly/2PPaa88

Background: In pulmonary hypertension subgroups, elevated pulmonary vascular resistance (PVR) of 3·0 Wood units or more is associated with poor prognosis. However, the spectrum of PVR risk in pulmonary hypertension is not known. To address this area of uncertainty, we aimed to analyse the relationship between PVR and adverse clinical outcomes in pulmonary hypertension. Methods: We did a retrospective cohort study of all patients undergoing right heart catheterisation (RHC) in the US Veterans Affairs health-care system (Oct 1, 2007–Sep 30, 2016). Patients were included in the analyses if data from a complete RHC and at least 1 year of follow-up were available. Both inpatients and outpatients were included, but individuals with missing mean pulmonary artery pressure (mPAP), pulmonary artery wedge pressure, or cardiac output were excluded. The primary outcome measure was time to all-cause mortality assessed by the Veteran Affairs vital status file. Cox proportional hazards models were used to assess the association between PVR and outcomes, and the mortality hazard ratio was validated in a RHC cohort from Vanderbilt University Medical Center (Sept 24, 1998–June 1, 2016). Findings: The primary cohort (N=40 082; 38 751 [96·7%] male; median age 66·5 years [IQR 61·1–73·5]; median follow-up 1153 days [IQR 570–1971]), included patients with a history of heart failure (23 201 [57·9%]) and chronic obstructive pulmonary disease (13 348 [33·3%]). We focused on patients at risk for pulmonary hypertension based on a mPAP of at least 19 mm Hg (32 725 [81·6%] of 40 082). When modelled as a continuous variable, the all-cause mortality hazard for PVR was increased at around 2·2 Wood units compared with PVR of 1·0 Wood unit. Among patients with a mPAP of at least 19 mm Hg and pulmonary artery wedge pressure of 15 mm Hg or less, the adjusted hazard ratio (HR) for mortality was 1·71 (95% CI 1·59–1·84; p

Background The measurements used to define pulmonary hypertension (PH) etiology, pulmonary arterial wedge pressure (PAWP), and left ventricular end-diastolic pressure (LVEDP) vary in clinical practice. We aimed to identify clinical features associated with measurement discrepancy between PAWP and LVEDP in patients with PH. Methods We extracted clinical data and invasive hemodynamics from consecutive patients undergoing concurrent right and left heart catheterization at Vanderbilt University between 1998 and 2014. The primary outcome was discordance between PAWP and LVEDP in patients with PH in a logistic regression model. Results We identified 2,270 study subjects (median age, 63 years; 53% men). The mean difference between PAWP and LVEDP was −1.6 mm Hg (interquartile range, −15 to 12 mm Hg). The two measurements were moderately correlated by linear regression (R = 0.6, P Conclusions Clinically meaningful disagreement between PAWP and LVEDP is common. Atrial fibrillation, rheumatic valve disease, and larger left atrial diameter are associated with misclassification of PH etiology when relying on PAWP alone. These findings are important because of the fundamental differences in the treatment of precapillary and postcapillary PH.

Pulmonary hypertension (PH) is common in patients with chronic kidney disease (CKD) and associated with increased mortality but the hemodynamic profiles, clinical risk factors, and outcomes have not been well characterized. Our objective was to define the hemodynamic profile and related risk factors for PH in CKD patients. We extracted clinical and hemodynamic data from Vanderbilt’s de-identified electronic medical record on all patients undergoing right heart catheterization during 1998–2014. CKD (stages III–V) was defined by estimated glomerular filtration rate thresholds. PH was defined as mean pulmonary pressure ≥ 25 mmHg and categorized into pre-capillary and post-capillary according to consensus recommendations. In total, 4635 patients underwent catheterization: 1873 (40%) had CKD; 1518 (33%) stage 3, 230 (5%) stage 4, and 125 (3%) stage 5. PH was present in 1267 (68%) of these patients. Post-capillary (n = 965, 76%) was the predominant PH phenotype among CKD patients versus 302 (24%) for pre-capillary ( P

Background Pulmonary hypertension (PH) is a common and morbid complication of left heart disease with 2 subtypes: isolated post-capillary pulmonary hypertension (Ipc-PH) and combined post-capillary and pre-capillary pulmonary hypertension (Cpc-PH). Little is known about the clinical or physiological characteristics that distinguish these 2 subphenotypes or if Cpc-PH shares molecular similarities to pulmonary arterial hypertension (PAH). Objectives The goal of this study was to test the hypothesis that the hemodynamic and genetic profile of Cpc-PH would more closely resemble PAH than Ipc-PH. Methods Vanderbilt University’s electronic medical record linked to a DNA biorepository was used to extract demographic characteristics, clinical data, invasive hemodynamic data, echocardiography, and vital status for all patients referred for right heart catheterization between 1998 and 2014. Shared genetic variants between PAH and Cpc-PH compared with Ipc-PH were identified by using pre-existing single-nucleotide polymorphism data. Results A total of 2,817 patients with PH (13% Cpc-PH, 52% Ipc-PH, and 20% PAH) were identified. Patients with Cpc-PH were on average 6 years younger, with more severe pulmonary vascular disease than patients with Ipc-PH, despite similar comorbidities and prevalence, severity, and chronicity of left heart disease. After adjusting for relevant covariates, the risk of death was similar between the Cpc-PH and Ipc-PH groups (hazard ratio: 1.14; 95% confidence interval: 0.96 to 1.35; p = 0.15) when defined according to diastolic pressure gradient. We identified 75 shared exonic single-nucleotide polymorphisms between Cpc-PH and PAH enriched in pathways involving cell structure, extracellular matrix, and immune function. These genes are expressed, on average, 32% higher in lungs relative to other tissues. Conclusions Patients with Cpc-PH develop pulmonary vascular disease similar to patients with PAH, despite younger age and similar prevalence of obesity, diabetes mellitus, and left heart disease compared with patients with Ipc-PH. An exploratory genetic analysis in Cpc-PH identified genes and biological pathways in the lung known to contribute to PAH pathophysiology, suggesting that Cpc-PH may be a distinct and highly morbid PH subphenotype.

Background Identification of occult diastolic dysfunction often requires invasive right heart catheterization with provocative maneuvers such as fluid challenge. Non‐invasive predictors of occult diastolic dysfunction have not been identified. We hypothesized that echocardiographic measures of diastolic function are associated with occult diastolic dysfunction identified at catheterization. Methods and Results We retrospectively examined hemodynamic and echocardiographic data from consecutive patients referred for right heart catheterization with fluid challenge from 2009 to 2017. A replication cohort of 52 patients who prospectively underwent simultaneous echocardiography and right heart catheterization before and after fluid challenge at Monaldi Hospital, Naples, Italy. In the retrospective cohort of 126 patients (83% female, 56+14 years), 27/126 (21%) had occult diastolic dysfunction. After adjusting for tricuspid regurgitant velocity and left atrial volume index, E velocity (odds ratio 1.8, 95% CI 1.1–2.9, P =0.01) and E/e′ (odds ratio 1.9, 95% CI 1.1–3, P =0.005) were associated with occult diastolic dysfunction with an optimal threshold of E/e′ >8.6 for occult diastolic dysfunction (sensitivity 70%, specificity 64%). In the prospective cohort, 5/52 (10%) patients had diastolic dysfunction after fluid challenge. Resting E/e′ (odds ratio 8.75, 95% CI 2.3–33, P =0.001) and E velocity (odds ratio 7.7, 95% CI 2–29, P =0.003) remained associated with occult diastolic dysfunction with optimal threshold of E/e′ >8 (sensitivity 73%, specificity 90%). Conclusions Among patients referred for right heart catheterization with fluid challenge, E velocity and E/e′ are associated with occult diastolic dysfunction after fluid challenge. These findings suggest that routine echocardiographic measurements may help identify patients like to have occult diastolic dysfunction non‐invasively.

Rationale: Red cell distribution width (RDW) is a prognostic factor in many diseases; however, its clinical utility remains limited because the relative value of RDW as a biomarker across disease states has not been established. Objectives: To establish an unbiased RDW disease hierarchy to guide the clinical use of RDW and to assess its relationship to cardiovascular hemodynamic and structural parameters. Methods: We performed phenome-wide association studies for RDW in discovery and replication cohorts derived from a deidentified electronic health record in nonanemic individuals. RDW values obtained within 30 days of echocardiogram or right heart catheterization were tested for association with structural and hemodynamic variables. Results: RDW was associated with 263 phenotypes in both men and women in the discovery cohort (n = 121,530), 48 of which replicated in an independent cohort (n = 2,039). The strongest associations were observed with pulmonary arterial hypertension (odds ratio [OR], 2.1; 95% confidence interval [CI], 1.9–2.3), chronic pulmonary heart disease (OR, 2.0; 95% CI, 1.9–2.2), and congestive heart failure (OR, 1.9; 95% CI, 1.8–2.0); P

Objective:To evaluate the effect of video laryngoscopy on the rate of endotracheal intubation on first laryngoscopy attempt among critically ill adults.Design:A randomized, parallel-group, pragmatic trial of video compared with direct laryngoscopy for 150 adults undergoing endotracheal intubation by

Although commonly encountered, patients with combined postcapillary and precapillary pulmonary hypertension (Cpc-PH) have poorly understood pulmonary vascular properties. The product of pulmonary vascular resistance and compliance, resistance-compliance (RC) time, is a measure of pulmonary vascular physiology. While RC time is lower in postcapillary PH than in precapillary PH, the RC time in Cpc-PH and the effect of pulmonary wedge pressure (PWP) on RC time are unknown. We tested the hypothesis that Cpc-PH has an RC time that resembles that in pulmonary arterial hypertension (PAH) more than that in isolated postcapillary PH (Ipc-PH). We analyzed the hemodynamics of 282 consecutive patients with PH referred for right heart catheterization (RHC) with a fluid challenge from 2004 to 2013 (cohort A) and 4,382 patients who underwent RHC between 1998 and 2014 for validation (cohort B). Baseline RC time in Cpc-PH was higher than that in Ipc-PH and lower than that in PAH in both cohorts (P < 0.001). In cohort A, RC time decreased after fluid challenge in patients with Ipc-PH but not in those with PAH or Cpc-PH (P < 0.001). In cohort B, the inverse relationship of pulmonary vascular compliance and resistance, as well as that of RC time and PWP, in Cpc-PH was similar to that in PAH and distinct from that in Ipc-PH. Our findings demonstrate that patients with Cpc-PH have pulmonary vascular physiology that resembles that of patients with PAH more than that of Ipc-PH patients. Further study is warranted to identify determinants of vascular remodeling and assess therapeutic response in this subset of PH.

Rationale: Hypoxemia is common during endotracheal intubation of critically ill patients and may predispose to cardiac arrest and death. Administration of supplemental oxygen during laryngoscopy (apneic oxygenation) may prevent hypoxemia.Objectives: To determine if apneic oxygenation increases the lowest arterial oxygen saturation experienced by patients undergoing endotracheal intubation in the intensive care unit.Methods: This was a randomized, open-label, pragmatic trial in which 150 adults undergoing endotracheal intubation in a medical intensive care unit were randomized to receive 15 L/min of 100% oxygen via high-flow nasal cannula during laryngoscopy (apneic oxygenation) or no supplemental oxygen during laryngoscopy (usual care). The primary outcome was lowest arterial oxygen saturation between induction and 2 minutes after completion of endotracheal intubation.Measurements and Main Results: Median lowest arterial oxygen saturation was 92% with apneic oxygenation versus 90% with usual care (95% con...

Parenteral prostacyclin therapy is the most efficacious pharmacologic treatment for pulmonary arterial hypertension (PAH), but clinical response is variable. We sought to identify clinical, hemodynamic, and genetic associations with response to prostacyclin therapy. We performed a retrospective analysis of patients within a de-identified electronic health record and associated DNA biobank. Patients with PAH and a right heart catheterization (RHC) in the six months before initiation of a parenteral prostacyclin were included. Responders were defined a priori by attainment of World Health Organization (WHO) functional class (FC) 2 or better at the time of repeat RHC within two years. We performed exploratory analyses to identify genomic associations with prostacyclin response. Of 129 patients identified, 54 met our criteria for “responders.” These patients were younger, more likely to be male, and were less likely to have connective tissue disease-related PAH. At follow-up, responders had improved hemodynamics, 6-min walk distance, and long-term survival. Baseline PA oxygen saturation (hazard ratio [HR] 0.568 [0.34–0.95]) and follow-up FC (HR = 2.57 [1.22–5.43]) were associated with survival. Prostacyclin responders were enriched in alleles related to cell development and circulatory system development and pathways related to aldosterone metabolism, cAMP signaling, and vascular smooth muscle contraction ( P

Background Transthoracic echocardiography ( TTE ) is used to estimate pulmonary artery systolic pressure, but an adequate tricuspid regurgitation velocity ( TRV ) needed to calculate pulmonary artery systolic pressure is not always present. It is unknown whether the absence of a measurable TRV signifies normal pulmonary artery pressure. Methods and Results We extracted hemodynamic, TTE , and clinical data from Vanderbilt's deidentified electronic medical record in all patients referred for right heart catheterization between 1998 and 2014. Pulmonary hypertension ( PH ) was defined as mean pulmonary artery pressure ≥25 mm Hg. We examined the prevalence and clinical correlates of PH in patients without a reported TRV . We identified 1262 patients with a TTE within 2 days of right heart catheterization. In total, 803/1262 (64%) had a reported TRV , whereas 459 (36%) had no reported TRV . Invasively confirmed PH was present in 47% of patients without a reported TRV versus 68% in those with a reported TRV ( P TRV yielded a negative predictive value for excluding PH of 53%. Right ventricular dysfunction, left atrial dimension, elevated body mass index, higher brain natriuretic peptide, diabetes mellitus, and heart failure were independently associated with PH among patients without a reported TRV . Conclusions PH is present in almost half of patients without a measurable TRV who are referred for both TTE and right heart catheterization. Clinical and echocardiographic features of left heart disease are associated with invasively confirmed PH in subjects without a reported TRV . Clinicians should use caution when making assumptions about PH status in the absence of a measurable TRV on TTE .

African Americans (AA) have a higher incidence of pulmonary hypertension (PH) risk factors. Few studies have examined the racial differences in the prevalence and etiology of PH and direct comparison of invasive hemodynamics between AAs and Caucasians has rarely been reported. In this study, we examined whether racial differences exist in patients referred for right heart catheterization (RHC) and hypothesized that AA race is an independent risk factor for PH and is associated with increased adjusted mortality. We extracted data for AA and Caucasian patients who underwent RHC at Vanderbilt between 1998 and 2014. Clinical information was obtained from Vanderbilt's Synthetic Derivative, a de-identified mirror of our Electronic Medical Record. A total of 4576 patients were analyzed, including 586 (13%) AAs and 3990 (87%) Caucasians. AAs were younger than Caucasians by an average of eight years, but had more prevalent heart failure, features of metabolic syndrome, and higher creatinine. AAs also had higher mean pulmonary artery pressure and pulmonary vascular resistance. After adjusting for relevant co-morbidities, the AA race is associated with 41% increased risk of PH (odds ratio [OR] = 1.41, 95% confidence interval [CI] = 1.12–1.79). Among patients with PH, AA race is associated with 24% increased adjusted mortality (hazard ratio [HR] = 1.24, 95% CI = 1.09–1.45). AAs were younger but had more prevalent cardiometabolic and renal disease and worse pulmonary hemodynamics. The AA race is an independent risk factor for PH. Among patients with PH, the AA race is associated with increased adjusted mortality. Future studies should focus on delineating whether genetic or environmental factors contribute to PH risk in AAs.

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 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.

Background Hypoxemia and hypotension are common complications during endotracheal intubation of critically ill adults. Verbal performance of a written, preintubation checklist may prevent these complications. We compared a written, verbally performed, preintubation checklist with usual care regarding lowest arterial oxygen saturation or lowest systolic BP experienced by critically ill adults undergoing endotracheal intubation. Methods A multicenter trial in which 262 adults undergoing endotracheal intubation were randomized to a written, verbally performed, preintubation checklist (checklist) or no preintubation checklist (usual care). The coprimary outcomes were lowest arterial oxygen saturation and lowest systolic BP between the time of procedural medication administration and 2 min after endotracheal intubation. Results The median lowest arterial oxygen saturation was 92% (interquartile range [IQR], 79-98) in the checklist group vs 93% (IQR, 84-100) with usual care ( P = .34). The median lowest systolic BP was 112 mm Hg (IQR, 94-133) in the checklist group vs 108 mm Hg (IQR, 90-132) in the usual care group ( P = .61). There was no difference between the checklist and usual care in procedure duration (120 vs 118 s; P = .49), number of laryngoscopy attempts (one vs one attempt; P = .42), or severe life-threatening procedural complications (40.8% vs 32.6%; P = .20). Conclusions The verbal performance of a written, preprocedure checklist does not increase the lowest arterial oxygen saturation or lowest systolic BP during endotracheal intubation of critically ill adults compared with usual care. Trial Registry ClinicalTrials.gov; No.: NCT02497729; URL: www.clinicaltrials.gov.

Background Hypoxemia is the most common complication during endotracheal intubation of critically ill adults. Intubation in the ramped position has been hypothesized to prevent hypoxemia by increasing functional residual capacity and decreasing the duration of intubation, but has never been studied outside of the operating room. Methods Multicenter, randomized trial comparing the ramped position (head of the bed elevated to 25°) with the sniffing position (torso supine, neck flexed, and head extended) among 260 adults undergoing endotracheal intubation by pulmonary and critical care medicine fellows in four ICUs between July 22, 2015, and July 19, 2016. The primary outcome was lowest arterial oxygen saturation between induction and 2 minutes after intubation. Secondary outcomes included Cormack-Lehane grade of glottic view, difficulty of intubation, and number of laryngoscopy attempts. Results The median lowest arterial oxygen saturation was 93% (interquartile range [IQR], 84%-99%) with the ramped position vs 92% (IQR, 79%-98%) with the sniffing position ( P = .27). The ramped position appeared to increase the incidence of grade III or IV view (25.4% vs 11.5%, P = .01), increase the incidence of difficult intubation (12.3% vs 4.6%, P = .04), and decrease the rate of intubation on the first attempt (76.2% vs 85.4%, P = .02), respectively. Conclusions In this multicenter trial, the ramped position did not improve oxygenation during endotracheal intubation of critically ill adults compared with the sniffing position. The ramped position may worsen glottic view and increase the number of laryngoscopy attempts required for successful intubation. Trial Registry ClinicalTrials.gov; No.: NCT02497729; URL: www.clinicaltrials.gov

We hypothesized that unbiased cluster analysis methods would identify distinct phenotypes of pulmonary arterial hypertension (PAH). We identified 191 patients with expert adjudicated PAH. A total of 47 clinical, laboratory, hemodynamic and echocardiographic variables were analyzed using Latent

There is a growing prevalence of diastolic heart failure worldwide. Right heart catheterization (RHC) with fluid challenge has been used to identify patients with occult diastolic dysfunction (DD), i.e. normal filling pressures at rest but elevated filling pressures with fluid challenge. Currently

Previously considered a disease isolated to the pulmonary circulation, pulmonary arterial hypertension is now being recognized as a systemic disorder that is associated with significant metabolic dysfunction. Numerous animal models have demonstrated the development of pulmonary arterial hypertension following the onset of insulin resistance, indicating that insulin resistance may be causal. Recent publications highlighting alterations in aerobic glycolysis, fatty acid oxidation, and the tricarboxylic acid cycle in the pulmonary circulation and right ventricle have expanded our understanding of the complex pathobiology of this disease. By targeting these derangements in metabolism, numerous researchers are investigating noninvasive techniques to monitor disease activity and therapeutics that address the underlying metabolic condition. In the following review, we will explore pre-clinical and clinical studies investigating the metabolic dysfunction seen in pulmonary arterial hypertension.

Discrimination of pre-capillary pulmonary hypertension (PH) and pulmonary venous hypertension (PVH) has clinical implications (both entities defined in Table 1). We examined the diagnostic concordance of pulmonary capillary wedge pressure (PCWP) and left ventricular end-diastolic pressure (LVEDP) in

Importance Thermodilution (Td) and estimated oxygen uptake Fick (eFick) methods are widely used to measure cardiac output (CO). They are often used interchangeably to make critical clinical decisions, yet few studies have compared these approaches as applied in medical practice. Objectives To assess agreement between Td and eFick CO and to compare how well these methods predict mortality. Design, Setting, and Participants This investigation was a retrospective cohort study with up to 1 year of follow-up. The study used data from the Veterans Affairs Clinical Assessment, Reporting, and Tracking (VA CART) program. The findings were corroborated in a cohort of patients cared for at Vanderbilt University, an academic referral center. Participants were more than 15 000 adults who underwent right heart catheterization, including 12 232 in the Veterans Affairs cohort between October 1, 2007, and September 30, 2013, and 3391 in the Vanderbilt cohort between January 1, 1998, and December 31, 2014. Exposures A single cardiac catheterization was performed on each patient with CO estimated by both Td and eFick methods. Cardiac output was indexed to body surface area (cardiac index [CI]) for all analyses. Main Outcomes and Measures All-cause mortality over 90 days and 1 year after catheterization. Results Among 12 232 VA patients (mean [SD] age, 66.4 [9.9] years; 3.3% female) who underwent right heart catheterization in this cohort study, Td and eFick CI estimates correlated modestly ( r = 0.65). There was minimal mean difference (eFick minus Td = −0.02 L/min/m 2 , or −0.4%) but wide 95% limits of agreement between methods (−1.3 to 1.3 L/min/m 2 , or −50.1% to 49.4%). Estimates differed by greater than 20% for 38.1% of patients. Low Td CI ( 2 compared with normal CI of 2.2-4.0 L/min/m 2 ) more strongly predicted mortality than low eFick CI at 90 days (Td hazard ratio [HR], 1.71; 95% CI, 1.47-1.99; χ 2 = 49.5 vs eFick HR, 1.42; 95% CI, 1.22-1.64; χ 2 = 20.7) and 1 year (Td HR, 1.53; 95% CI, 1.39-1.69; χ 2 = 71.5 vs eFick HR, 1.35; 1.22-1.49; χ 2 = 35.2). Patients with a normal CI by both methods had 12.3% 1-year mortality. There was no significant additional risk for patients with a normal Td CI but a low eFick CI (12.9%, P = .51), whereas a low Td CI but normal eFick CI was associated with higher mortality (15.4%, P = .001). The results from the Vanderbilt cohort were similar in the context of a more balanced sex distribution (46.6% female). Conclusions and Relevance There is only modest agreement between Td and eFick CI estimates. Thermodilution CI better predicts mortality and should be favored over eFick in clinical practice.

Background: Pulmonary hypertension (PH) is a common clinical problem. Transthoracic echocardiography (TTE) is used to estimate pulmonary arterial pressure (PAP), but an adequate tricuspid regurgitation velocity (TRV) needed to calculate PAP is not always present. It is unknown whether the absence of

Pulmonary hypertension (PH) is common in chronic kidney disease (CKD), but the hemodynamic etiology (precapillary vs. post capillary) and outcomes across CKD stages have not been well characterized. We extracted clinical and hemodynamic data from our de-identified electronic medical record in all

We read with interest the report by Al-Naamani et al. [(1)][1] and the editorial by Borlaug [(2)][2] on the prognostic value of the diastolic pressure gradient (DPG) in heart failure patients with preserved ejection fraction. The DPG did not predict mortality, which is in agreement with results

Supplemental material for Racial differences in patients referred for right heart catheterization and risk of pulmonary hypertension by Bin Q. Yang, Tufik R. Assad, Jared M. O'Leary, Meng Xu, Stephen J. Halliday, Reid W. D'Amico, Eric H. Farber-Eger, Quinn S. Wells, Anna R. Hemnes and Evan L. Brittain in Pulmonary Circulation

Supplemental material for Clinical and genetic associations with prostacyclin response in pulmonary arterial hypertension by Stephen J. Halliday, Meng Xu, Timothy E. Thayer, Jonathan D. Mosley, Quanhu Sheng, Fei Ye, Eric H. Farber-Eger, Meredith E. Pugh, Ivan R. Robbins, Tufik R. Assad, James D. West, Evan L. Brittain and Anna R. Hemnes in Pulmonary Circulation

Supplemental material for Racial differences in patients referred for right heart catheterization and risk of pulmonary hypertension by Bin Q. Yang, Tufik R. Assad, Jared M. O'Leary, Meng Xu, Stephen J. Halliday, Reid W. D'Amico, Eric H. Farber-Eger, Quinn S. Wells, Anna R. Hemnes and Evan L. Brittain in Pulmonary Circulation

Supplemental material for Clinical and genetic associations with prostacyclin response in pulmonary arterial hypertension by Stephen J. Halliday, Meng Xu, Timothy E. Thayer, Jonathan D. Mosley, Quanhu Sheng, Fei Ye, Eric H. Farber-Eger, Meredith E. Pugh, Ivan R. Robbins, Tufik R. Assad, James D. West, Evan L. Brittain and Anna R. Hemnes in Pulmonary Circulation