Pulmonary Artery Wedge Research Articles

Equine exercise-induced pulmonary hemorrhage: the role of high left-heart pressures secondary to exercise-induced hypervolemia, and high inspiratory pressures.

Exercise-induced hypervolemia is normal in racehorses. Stress failure of the blood-gas barrier causes EIPH and occurs when the transmural pulmonary capillary (Pcap)-alveolar pressure difference (Ptm) exceeds the barrier's stress failure threshold. Why Pcap increases is incompletely understood. We hypothesized that alterations in blood volume (BV) affect left ventricular (LV) and pulmonary arterial wedge (PAW) pressures, and Pcap, and correspondingly affect EIPH severity. Six thoroughbreds with EIPH underwent treadmill exercise at the same speed (≈11.9m/s [11.1, 12.2]; median [IQR]) before (≈119%V̇O2max; B), 2hr after 14L depletion of blood (≈132%V̇O2max; D) and 2hr after reinfusing the blood (≈111%V̇O2max; R). LV, pulmonary arterial (PAP), PAW and intrapleural (Ppl) pressures were measured throughout exercise. Pcap = (PAP+PAW)/2 and Ptm = Pcap - Ppl. EIPH severity was assessed 60min post-exercise by tracheoendoscopy (EIPHgrade) and bronchoalveolar lavage erythrocyte count (BALRBC). A mixed-effect model and Tukey post-hoc test analyzed effects of BV changes on LV, PAW, Pcap, Ppl, Ptm and EIPH. p≤0.05 was significant. EIPH severity was affected by BV (EIPHgrade: p=0.01, BALRBC: p=0.003). Peak Ptm was not different between B (146mmHg [140; 151]) and R (151mmHg [137; 160]) but was lower for D (128mmHg [127; 130]; B: p=0.005, R: p=0.02). LV end diastolic pressure (LVED) was correlated with maxPcap (r2=0.52, p=0.001). Ppl was unaffected by changes in BV. Vascular pressures and Ppl fluctuated constantly during exercise and independently influenced Ptm. Circulating BV but not exercise intensity had a major effect on LVED, Pcap and Ptm, and was correlated with EIPH severity in thoroughbred racehorses (r2=0.48, p=0.001).

Fontan hemodynamics in adults with obesity compared to overweight and normal body mass index: a retrospective invasive exercise study.

The effects of obesity on Fontan hemodynamics are poorly understood. Accordingly, we assessed its impact on exercise invasive hemodynamics and exercise capacity. Seventy-seven adults post-Fontan undergoing exercise cardiac catheterization (supine cycle protocol) were retrospectively identified using an institutional database and categorized according to the presence of obesity (body mass index [BMI] >30 kg/m2) and overweight/normal BMI (BMI≤30 kg/m2). There were 18 individuals with obesity (BMI 36.4±3 kg/m2) and 59 (BMI 24.1±3.6 kg/m2) with overweight/normal BMI. Peak oxygen consumption (VO2) on noninvasive cardiopulmonary exercise testing was lower in patients with obesity (15.6±3.5 vs 19.6±5.8 ml/kg/min, p=0.04). At rest, systemic flow (Qs) (7.0 [4.8; 8.3] vs 4.8 [3.9; 5.8] l/min, p=0.001), pulmonary artery (PA) pressure (16.3±3.5 vs 13.1±3.5 mmHg, p=0.002), and PA wedge pressure (PAWP) (11.7±4.4 vs 8.9±3.1 mmHg, p=0.01) were higher, while arterial O2 saturation was lower (89.5% [86.5; 92.3] vs 93% [90; 95]) in obesity compared to overweight/normal BMI. Similarly, patients with obesity had higher exercise PA pressure (29.7±6.5 vs 24.7±6.8 mmHg, p=0.01) and PAWP (23.0±6.5 vs 19.8±7.3 mmHg, p=0.047), but lower arterial O2 saturation (82.4±7.0% vs 89% [85; 92], p=0.003). Adults post-Fontan with obesity have worse aerobic capacity, increased Qs, higher filling pressures, and decreased arterial O2 saturation compared to those with overweight/normal BMI, both at rest and during exercise, mirroring the findings observed in the obesity phenotype of heart failure with preserved ejection fraction. Whether treating obesity and its cardiometabolic sequelae in Fontan patients will improve hemodynamics and outcomes requires further study.

Functional Capacity Assessment in Adults After Fontan Palliation: A Cardiopulmonary Exercise Test–Invasive Exercise Hemodynamics Correlation Study

While cardiopulmonary exercise testing (CPET) parameters have known prognostic value in adults post-Fontan, there is limited data correlating treadmill CPET with invasive exercise hemodynamics. Furthermore, the invasive hemodynamic underpinnings of exercise limitations have not been thoroughly investigated. This is retrospective analysis of 55 adults (≥18 years) post-Fontan who underwent treadmill CPET prior to invasive exercise hemodynamic testing via supine cycle protocol between November 2018 and April 2023. Median age was 32.2 (24.1; 37.2) years. Peak heart rate (HR) was 139.7±28.1 bpm and peak oxygen consumption (VO2) was 19.1±5.7 ml/kg/min (47.4±13.5% predicted). VO2/HR was directly related to exercise stroke volume index (Svi) (r=0.50; p=0.0002), while no association was seen with exercise arterio-mixed venous O2 content difference (r=0.14; p=0.32). Peak HR was inversely related to exercise pulmonary artery (PA) pressures (r=-0 61; p<0.0001) and PA wedge pressures (PAWP) (r=-0.61; p<0.0001). Moreover, % predicted VO2 was inversely related to exercise PA pressures (r=-0.50; p<0.0001) and PAWP (r=-0.55; p<0.0001). Peak VO2 ≤19.1 ml/kg/min had a sensitivity of 81% and specificity of 76% (AUC 0.82) for predicting a ΔPAWP/ΔQs ratio >2 mmHg/l/min and/or a ΔPA/ΔQp ratio >3 mmHg/l/min, while a predicted peak VO2 ≤48% had a sensitivity of 74% and specificity of 81% (AUC 0.79) for the same parameters. In summary, lower peak HR and lower peak VO2 were associated with higher exercise PAWP and PA pressure. Peak VO2 ≤48% predicted provided the optimal cut-off for predicting elevated indexed exercise PAWP or PA pressures, thus low peak VO2 should alert clinicians of abnormal underlying hemodynamics.

Exercise catheterization in adults post-Fontan with normal and abnormal haemodynamic criteria: Insights into normal Fontan physiology.

The normal (i.e. expected) haemodynamics in adults post-Fontan remain poorly delineated. Moreover, the definitions of elevated exercise pulmonary artery (PA) and PA wedge pressure (PAWP) for this population have not been described. Seventy-two adults post-Fontan undergoing exercise catheterization were categorized into abnormal (Group I, n = 59; defined as resting mean PA ≥14 mmHg and/or PAWP ≥12 mmHg, ΔPAWP/Δsystemic flow [Qs] >2 mmHg/L/min, and/or ΔPA/Δpulmonary flow >3 mmHg/L/min) and normal (Group II, n = 13) haemodynamics. Thirty-nine patients with non-cardiac dyspnoea (NCD) were included as controls. There was no difference in exercise arterial oxygen saturation (87% [81-92] vs. 89% [85-93], p = 0.29), while exercise PA pressure (27 [23-31] vs. 16 [14.5-19.5] mmHg, p < 0.001) and PAWP were higher (21 [18-28] vs. 12 [8-14] mmHg, p < 0.001) in Group I. At peak exercise, Group I had lower heart rate (97 [81-120] vs. 133 [112.5-147.5] bpm, p < 0.001) and Qs response (67.3 [43.8-93.1] vs. 105.9 (82-118.5) % predicted, p < 0.001) than Group II. Exercise superior vena cava pressures were higher (16 [14-22.5] vs. 5.5 [3-7.3] mmHg, p < 0.001) and arterial oxygen saturation lower (89% [85-93] vs. 97% [96-98], p < 0.001) in Group II compared to NCD, while no differences in PAWP, stroke volume index, heart rate, or Qs response were seen. If defined as two standard deviations above mean values for Group II, elevated PAWP and mean PA pressure post-Fontan would correspond to 20.6 mmHg and 25.8 mmHg, respectively. PAWP >20 mmHg and mean PA pressure >25 mmHg could be used to define elevated values during exercise in adults post-Fontan. The major discrepancy in exercise haemodynamics among Group II compared to controls appears to be the degree of systemic venous hypertension and arterial desaturation.

Impaired left atrial reservoir function associated with large v wave in patients with transthyretin amyloid cardiomyopathy

Abstract Background Impaired atrial function, in addition to ventricular diastolic dysfunction, is one of the hallmarks of cardiac amyloidosis (ATTR-CM). Two-dimensional speckle tracking echocardiography is a useful technique for quantitative assessment of LA stiffness. A large v wave on pulmonary artery wedge (PAW) pressure waveform is the findings suggesting LA overload and impaired LA reservoir function. Although large v waves on PAW pressure waveforms are sometimes observed in ATTR-CM patients, their hemodynamic background and clinical significance have not been well described. Purpose To investigate the clinical importance of LA function obtained by echocardiography and PAW pressure waveform and the association of enhanced large PAW v wave to clinical outcomes in ATTR-CM patients. Methods We retrospectively analyzed central hemodynamics in 136 ATTR-CM patients without severe mitral regurgitation. Large v wave was defined 10 mmHg above mean PAW pressure. We divided 136 ATTR-CM into large v wave group (n = 27) and non-large v wave group (n = 109), and compared the differences in baseline parameters and echocardiographic parameters. Results Patients in the large v wave group showed higher mean PAW pressure (24mmHg vs. 14mmHg, p&amp;lt;0.0001). There were no significant differences in age, prevalence of atrial fibrillation, high-sensitivity cardiac troponin T levels (0.060 ng/ml vs. 0.044 ng/mL, p = 0.341), B-type natriuretic peptide levels (188.3 pg/ml vs. 178.7 pg/mL, p = 0.386). In addition, LV ejection fraction, LA diameter, E/e` and cardiac index showed no significant differences between the two groups. However, LA peak longitudinal strain (LS) and LS rate (LSR), evaluation of LA reservoir function, expressed significant depression in large v wave group (LS: 6.24 % vs 9.21 %, p&amp;lt;0.0001, LSR: 0.29 1/s vs 0.38 1/s, p = 0.005). Conclusions In ATTR-CM patients, the impaired LA reservoir function associated with extent of large v wave on PAW pressure. This result suggested that impaired LA function may be useful for assessing the progression of ATTR-CM and the deterioration of central hemodynamics.

Alterations of pulmonary vascular afterload in exercise‐induced pre‐ and post‐capillary pulmonary hypertension

Exercise imposes increased pulmonary vascular afterload based on rises in pulmonary artery (PA) wedge pressure, declines in PA compliance, and resistance-compliance time. In health, afterload stress stabilizes during steady-state exercise. Our objective was to examine alterations of these exercise-associated stresses in states of pre- and post-capillary pulmonary hypertension (PH). PA hemodynamics were evaluated at rest, 2 and 7min of steady-state exercise at moderate intensity in patients who exhibited Pre-capillary (n=22) and post-capillary PH (n=22). Patients with normal exercise hemodynamics (NOR-HD) (n=32) were also studied. During exercise in all groups, PA wedge pressure increased at 2min, with no further change at 7min. In post-capillary PH and NOR-HD, increases in PA diastolic pressure and diastolic pressure gradient remained stable at 2 and 7min of exercise, while in pre-capillary PH, both continued to increase at 7 min. The behavior of the diastolic pressure gradient was linearly related to the duration of resistance-compliance time at rest (r2 =0.843) and exercise (r2 =0.760). Exercise resistance-compliance time was longer in pre-capillary PH associated with larger increases in diastolic pressure gradient. Conversely, resistance-compliance time was shortest in post-capillary PH compared to pre-capillary PH and NOR-HD and associated with limited increases in exercise diastolic pressure gradient. During steady-state, modest-intensity exercise-specific patterns of pulmonary vascular afterload responses were observed in pre- and post-capillary PH relative to NOR-HD. Longer resistance-compliance time related to greater increases in PA diastolic pressure and diastolic pressure gradients in pre-capillary PH, while shorter resistance-compliance time appeared to limit these increases in post-capillary PH.

PS-C05-3: ESTIMATION OF PULMONARY PULSATILE ARTERIAL LOAD IN PATIENTS UNDERGOING INVESTIGATION FOR PULMONARY HYPERTENSION

Objective: Diagnosis of pulmonary hypertension (PH) is typically confirmed by elevation of the pulmonary artery (PA) pressure and/or pulmonary vascular resistance (PVR). However, PVR may overlook the pulsatile component of RV hydraulic work which involves the dynamic interplay between PA resistance and compliance. PA vascular impedance (PVZ) offers a more comprehensive assessment of RV and PA load. This study aims to apply a method of PA pulsatile load as PVZ determination in a cohort of patients referred for PH evaluation. Design and Methods: Fifty-eight participants (71% females, mean 53 ± 18 years) were recruited, and underwent right heart catheterisation (RHC) to measure systolic (sPAP), diastolic (dPAP), mean (mPAP), and PA wedge pressures (PAWP), cardiac output (CO) and PVR; classified as precapillary PH (PrecPH), isolated postcapillary PH (IpcPH), combined PH (CpcPH) and control group. PA flows were recorded using 3T cardiac magnetic resonance (CMR); RV volume (V) were obtained by contouring endocardial and epicardial borders on the short axis at end diastolic (ED) and end systolic (ES) phases, and ejection fraction (RVEF) was calculated as (RVEDV - RVESV)/RVEDVx100. Volumetric flow was measured using phase-contrast velocity quantification using 3T cardiac magnetic resonance (CMR). PVZ was expressed as the relationship of pulsatile pressure to pulsatile flow in the frequency domain. Results: 76% of patients had evidence of PH on RHC (8 PrecPH, 17 IpcPH, 9 CpcPH). CpcPH and PrecPH patients tended to show poorer RV contractility compared with control and IpcPH groups, albeit not statistically significant. PVZ was highest in patients with PrecPH and CpcPH, while lowest in those with IpcPH. A correlation analysis was performed to seek association between mPAP, PVR and PVZ and other variables thought to be related to PH. In PrecPH, increased mPAP was found to be associated with raised PVR (p &lt; 0.001; R = 0.94) and PVZ (p &lt; 0.001; R = 0.78). However, there was no association between elevated mPAP and PVZ in IpcPH and CpcPH, despite a significant correlation with PVR (IpcPH P = 0.03, R = 0.55; CpcPH P = 0.01, R = 0.77). Conclusion: We describe a straightforward method to measure and compare pulsatile vascular load of the systemic and pulmonary circulations simultaneously, allowing further quantification of systemic/pulmonary vascular interactions. Further research is required to evaluate small-vessel contributions to the arterial circulation, especially in the pulmonary system.

Enormous Pulmonary Arteries and a Late Diagnosis of a Common Congenital Cardiac Issue: A Case Report

Background: Noonan’s syndrome is the second most common congenital cardiac syndrome after Down syndrome. Classically it is associated with pulmonary stenosis, Hypertrophic Cardiomyopathy (HCM), and Atrial Septal Defects (ASD). Late presentations, milder phenotypes and atypical presentations can occur in adult life and have cardiovascular implications. Case Summary: A 62-year-old presented to the emergency department with chest pain and atrial fibrillation with fast ventricular rate and RBBB morphology. A transthoracic echocardiogram demonstrated a massive Pulmonary Artery (PA), concerning for pulmonary hypertension and an atrial septal defect (ASD). Right heart catheterization indicated enormous coronary artery ectasia but normal PA pressures and wedge pressures. He was identified as a late presentation of Noonan’s syndrome on subsequent genetic testing. Discussion: Some series indicate a prevalence of 1 in 100 for mild Noonan’s syndrome phenotypes, highlighting the importance of understanding its cardiac presentations. In this case, we present a man with minimal symptoms but gross pathologies of his pulmonary and coronary arteries. Furthermore, pulmonary artery dilatation without pulmonary valve pathology has not been reported in the literature, and only a few reports of coronary artery ectasia are reported.

Pulmonary vascular disease in pulmonary hypertension due to left heart disease: pathophysiologic implications.

Pulmonary hypertension (PH) and pulmonary vascular disease (PVD) are common and associated with adverse outcomes in left heart disease (LHD). This study sought to characterize the pathophysiology of PVD across the spectrum of PH in LHD. Patients with PH-LHD [mean pulmonary artery (PA) pressure >20 mmHg and PA wedge pressure (PAWP) ≥15 mmHg] and controls free of PH or LHD underwent invasive haemodynamic exercise testing with simultaneous echocardiography, expired air and blood gas analysis, and lung ultrasound in a prospective study. Patients with PH-LHD were divided into isolated post-capillary PH (IpcPH) and PVD [combined post- and pre-capillary PH (CpcPH)] based upon pulmonary vascular resistance (PVR <3.0 or ≥3.0 WU). As compared with controls (n = 69) and IpcPH-LHD (n = 55), participants with CpcPH-LHD (n = 40) displayed poorer left atrial function and more severe right ventricular (RV) dysfunction at rest. With exercise, patients with CpcPH-LHD displayed similar PAWP to IpcPH-LHD, but more severe RV-PA uncoupling, greater ventricular interaction, and more severe impairments in cardiac output, O2 delivery, and peak O2 consumption. Despite higher PVR, participants with CpcPH developed more severe lung congestion compared with both IpcPH-LHD and controls, which was associated lower arterial O2 tension, reduced alveolar ventilation, decreased pulmonary O2 diffusion, and greater ventilation-perfusion mismatch. Pulmonary vascular disease in LHD is associated with a distinct pathophysiologic signature marked by greater exercise-induced lung congestion, arterial hypoxaemia, RV-PA uncoupling, ventricular interdependence, and impairment in O2 delivery, impairing aerobic capacity. Further study is required to identify novel treatments targeting the pulmonary vasculature in PH-LHD.

Ramping Up the Pressure on the Right Ventricle.

HomeCirculation: Heart FailureVol. 15, No. 6Ramping Up the Pressure on the Right Ventricle Free AccessResearch ArticlePDF/EPUBAboutView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citationsPermissions ShareShare onFacebookTwitterLinked InMendeleyRedditDiggEmail Jump toFree AccessResearch ArticlePDF/EPUBRamping Up the Pressure on the Right Ventricle Simone L. Savaris, MD, MSc, Isaac S. Chang, PhD, Stephen P. Wright, MSc, PhD and Susanna Mak, MD, PhD Simone L. SavarisSimone L. Savaris Correspondence to: Simone L. Savaris, MD, MSc, Division of Cardiology, Mount Sinai Hospital, 600 University Ave, Toronto, ON M5G 1X5, Canada. Email E-mail Address: [email protected] https://orcid.org/0000-0002-9049-1805 Division of Cardiology, Mount Sinai Hospital, Toronto, ON, Canada (S.L.S., S.M.). Search for more papers by this author , Isaac S. ChangIsaac S. Chang Mount Sinai Hospital, Toronto, ON, Canada (I.S.C.). Search for more papers by this author , Stephen P. WrightStephen P. Wright Centre for Heart, Lung, and Vascular Health, School of Health and Exercise Sciences, University of British Columbia, Kelowna, Canada (S.P.W.). Search for more papers by this author and Susanna MakSusanna Mak https://orcid.org/0000-0003-2193-602X Division of Cardiology, Mount Sinai Hospital, Toronto, ON, Canada (S.L.S., S.M.). Search for more papers by this author Originally published21 Apr 2022https://doi.org/10.1161/CIRCHEARTFAILURE.122.009671Circulation: Heart Failure. 2022;15Other version(s) of this articleYou are viewing the most recent version of this article. Previous versions: April 21, 2022: Ahead of Print A 49-year-old man underwent Heartmate 3 left ventricular assist device implantation as bridge to transplant candidacy for cardiogenic shock due to an ischemic cardiomyopathy which was complicated by a flail mitral valve leaflet resulting in severe regurgitation.Right heart catheterization was performed to assess residual pulmonary hypertension. Right ventricular (RV) and pulmonary artery (PA) pressures were recorded continuously. At baseline, mean PA pressure was 24 mm Hg and pulmonary vascular resistance was 3.0 WU at a speed of 5600 rpm. PA wedge pressure was altered by adjusting speed from 4600 to 5800 rpm. Further increases in speed did not change hemodynamics. Vasoreactivity testing with sodium nitroprusside was also used, based on recent evidence that even mildly elevated PA loading confers increased mortality risk.1,2 Pmax, a theoretical maximal RV systolic pressure derived by extrapolating the isovolumic portions of the waveform, was averaged over 10 cardiac cycles to calculate a single-beat estimate of RV end-systolic elastance, along with PA elastance and the end-systolic elastance:elastance ratio.3The incremental decline in the PA wedge pressure with attenuation of the V wave can be seen as left ventricular assist device speed was increased, and then with infusion of the vasodilator sodium nitroprusside (Figure and Table from left to right). Concomitant reductions in PA pressure and elastance were associated with shortening of the time to peak RVSP, and improved RV-PA coupling as reflected by increasing end-systolic elastance:elastance ratio. Importantly, mixed venous O2 saturation, stroke volume, and cardiac output increased steadily with afterload reduction.Table. Hemodynamics and Values Derived From Single-Beat Estimation of the Ees:Ea RatioUnsupportedRelatively unsupportedBaselineSNP (0.75 μg/kg per min)SNP (1.5 μg/kg per min)Speed4600 rpm5000 rpm5600 rpm5600 rpm5600 rpmMAP, mm Hg9492969065PAWP (a/v/mean), mm Hg18/37/1817/35/1710/24/1011/28/115/9/3PAP (S/D/M), mm Hg51/14/3047/13/2941/10/2441/9/2432/5/17RAP, mm Hg44320PVR, d/s per cm5192200240176168SVR, d/s per cm51532143613781193765MVO2, %61.663.365.168.573.3CO, L/min4.74.95.45.96.8SVi, mL/m2 per beat3941454955RVSP, mm Hg4946424334Time to RVSP, ms318226221210146Pmax, mm Hg166136143147142Ea, mm Hg/mL0.60.470.370.340.2Ees:Ea ratio2.72.73.63.76.7CO indicates cardiac output; Ea, pulmonary artery arterial elastance; Ees, RV end-systolic elastance; MAP, mean arterial pressure; MVO2, mixed venous oxygen saturation; PAP, pulmonary artery pressure; PAWP, pulmonary artery wedge pressure; Pmax, maximal predicted RV pressure; PVR, pulmonary vascular resistance; RAP, right atrium pressure; RV, right ventricle; RVSP, right ventricle systolic pressure; SNP, sodium nitroprusside; SVi, stroke volume index; and SVR, systemic vascular resistance.Download figureDownload PowerPointFigure. The figure shows that with alterations in speed and with a vasodilator challenge (from left to right), pulmonary artery wedge pressure (PAWP) and pulmonary artery pressure (PAP) declined, with measurable changes in the morphology of the right ventricular pressure (RVP) waveform. Pmax, the theoretical maximal RVP, and graphical representations of the coordinates employed for single-beat estimation of RV end-systolic elastance (Ees) are also illustrated. Ea indicates pulmonary artery arterial elastance; Pes, estimated end-systolic pressure; Pmax, maximal predicted RVP; RVSP, right ventricle systolic pressure; SNP, sodium nitroprusside; and SV, stroke volume.This case reinforces the effect of systemic vasodilation and venodilation to optimize hemodynamics in the setting of heart failure with reduced ejection fraction, mitral regurgitation, and a continuous flow left ventricular assist device. The upstream effects of adequate unloading of the left ventricle to improve the function of the RV-PA circulatory unit are also illustrated.Article InformationSources of FundingNone.Disclosures None.FootnotesFor Sources of Funding and Disclosures, see page 645.Correspondence to: Simone L. Savaris, MD, MSc, Division of Cardiology, Mount Sinai Hospital, 600 University Ave, Toronto, ON M5G 1X5, Canada. Email simonelouise.[email protected]ca

Abstract 11199: Insulin-Like Growth Factor Binding Protein-4 is Associated with Pulmonary Arterial Hypertension Severity and Survival

Introduction: Pulmonary arterial hypertension (PAH) results in progressive elevation of pulmonary vascular resistance and right heart failure. Insulin like growth factor binding proteins (IGFBPs) are a family of growth factor modifiers. As increased IGFBP4 expression is associated with vascular proliferation in lung cancer, it may also be associated with PAH severity. Hypothesis: Elevated IGFBP4 is associated with worse disease severity and survival in PAH. Methods: Using enzyme-linked immunosorbent assays (ELISA), we evaluated serum IGFBP4 in a multicenter PAH cohort, the NHLBI PAHBiobank (N=2571), and healthy controls (N=125). Hemodynamic and functional measures were used to assess IGFBP4’s association to PAH severity and survival. Spearman’s rank correlation test and Kruskal Wallis test were used for correlations. IGFBP4 was dichotomized at the median and analyzed by Kaplan-Meier survival and Cox proportional Hazard regression. Results: Serum IGFBP4 levels were significantly elevated (p&lt;0.0001) compared to controls. After adjustment for age and sex, IGFBP4 above mean was associated with a 40 meter shorter six minute walk distance (95%CI, -55 to -25, p=&lt;0.001). In the IPAH subtype only, higher IGFBP4 was associated with higher mean right atrial pressures (2 mmHg; 95%CI, 1.2 to 2.9, p=&lt;0.001), mean pulmonary arterial pressures (2.0 mmHg; 95%CI, 0.09 to 4.0, p=0.041) and pulmonary capillary wedge pressures (0.75mmHg; 95%CI, 0.18 to 1.3, p=0.010). Cox multivariable analysis demonstrated higher serum IGFBP4 as an independent predictor of survival in the overall PAHB cohort (See Figure 1; HR, 3.6; 95% CI, 2.6-5.0), with worse outcomes for CHD-APAH (HR, 9.9; CI, 2.2-45) and IPAH (HR, 5.3; 95% CI, 2.9-9.7). Conclusions: Higher circulating IGFBP4 levels are significantly associated with worse PAH severity and shorter survival. Dysregulation of IGF metabolism/growth axis could play a significant role in PAH cardio-pulmonary pathobiology.

Elevated Left and Right Atrial Pressures Long-Term After Atrial Septal Defect Correction: An Invasive Exercise Hemodynamic Study.

BackgroundDespite correction of the atrial septal defect (ASD), patients experience atrial fibrillation frequently and have increased morbidity and mortality. We examined physical capacity, cardiac performance, and invasive hemodynamics in patients with corrected ASD.Methods and ResultsThirty‐eight corrected patients with isolated secundum ASD and 19 age‐matched healthy controls underwent right heart catheterization at rest and during exercise with simultaneous expired gas assessment and echocardiography. Maximum oxygen uptake was comparable between groups (ASD 32.7±7.7 mL O2/kg per minute, controls 35.2±7.5 mL O2/kg per minute, P=0.3), as was cardiac index at both rest and peak exercise. In contrast, pulmonary artery wedge v wave pressures were increased at rest and peak exercise (rest: ASD 14±4 mm Hg, controls 10±5 mm Hg, P=0.01; peak: ASD 25±9 mm Hg, controls 14±9 mm Hg, P=0.0001). The right atrial v wave pressures were increased at rest but not at peak exercise. The transmural filling pressure gradient (TMFP) was higher at peak exercise among patients with ASD (10±6 mm Hg, controls 7±3 mm Hg, P=0.03). One third of patients with ASD demonstrated an abnormal hemodynamic exercise response defined as mean pulmonary artery wedge pressure ≥25 mm Hg and/or mean pulmonary artery pressure ≥35 mm Hg at peak exercise. These patients had significantly elevated peak right and left atrial a wave pressures, right atrial v wave pressures, pulmonary artery wedge v wave pressures, and transmural filling pressure compared with both controls and patients with ASD with a normal exercise response.ConclusionsPatients with corrected ASD present with elevated right and in particular left atrial pressures at rest and during exercise despite preserved peak exercise capacity. Abnormal atrial compliance and systolic atrial function could predispose to the increased long‐term risk of atrial fibrillation.Registration Informationclinicaltrials.gov. Identifier: NCT03565471.

The impact of chronic heart failure on heart remodeling in patients with atrial fibrillation

Atrial fibrillation (AF) and chronic heart failure (CHF) often coexist due to common pathophysiological mechanisms and risk factors. However, the effect of CHF on heart remodeling in patients with permanent AF has been insufficiently studied. The aim: to study the influence of CHF on changes in structural and geometric parameters and diastolic function of the heart in patients with permanent AF. Materials and methods. The study included 100 patients (men – 60 % (n = 60); women – 40 % (n = 40)) with CHF of ischemic origin and AF, stage II AB, NYHA II-IV FC, and 16 coronary heart disease patients (men – 62.5 % (n = 10), women – 37.5 % (n = 6)) with AF without signs of CHF. Patients were comparable in age (P = 0.267), height (p = 0.406), weight (P = 0.518), body surface area (P = 0.388). Doppler echocardiography was performed on the device Esaote MyLab Eight (Italy) according to standard methods. Results. Patients with AF and signs of CHF were dominated by individuals with eccentric hypertrophy (49 % vs. 19 %; P = 0.0270), and patients with AF without signs of CHF – with eccentric remodeling (0 % vs. 25 %; P = 0.0001). Patients with AF and signs of CHF had significantly higher systolic pressure in the pulmonary artery (54.85 ± 14.23 mm Hg vs. 42.99 ± 11.94 mm Hg; P = 0.028) and pulmonary capillary wedge pressure (PCWP) (12.18 (9.80; 15.33) mm Hg vs. 8.92 (7.62; 10.50) mm Hg; P = 0.005) than patients with AF without signs of CHF, indicating more pronounced pulmonary hypertension and a more significant increase in left atrium pressure. AF patients with signs of CHF demonstrated significantly higher left ventricle end-diastolic pressure (LVEDP), as evidenced by the parameters: E\E’ medial (9.87 ± 5.24 vs. 6.15 ± 1.39; P = 0.001), E/E’ mean (8.38 ± 4.21 vs. 6.06 ± 1.97; P = 0.005), e’ medial (9.96 ± 3.79 cm/s vs. 12.81 ± 3.60 cm/s; P = 0.004). AF patients with signs of CHF had decreased LV EF (55.58 ± 14.65 % vs. 65.44 ± 10.87 %; P = 0.006), systolic velocity of the medial fibrous ring of the mitral valve S (6.92 ± 2.41 cm/s vs. 8.40 ± 2.03 cm/s; P = 0.015), and significantly higher values of TEI RV (0.58 ± 0.16 c. u. vs. 0.48 ± 0.11 c. u.; P = 0.011), but decreased TAPSE values (16.22 ± 4.60 mm vs. 19.54 ± 5.00 mm; P = 0.067), indicating more pronounced systolic dysfunction of both ventricles. Conclusions. Comorbidity of CHF and AF in patients is accompanied by the increased percentage of eccentric hypertrophy (49 %; P = 0.027), more pronounced systolic dysfunction of the left and right ventricles, increased LVEDP, PCWP, systolic pressure in the pulmonary artery, dilation of the inferior vena cava.

Exercise hemodynamics in heart failure patients with preserved and mid-range ejection fraction: key role of the right heart.

We sought to explore whether classification of patients with heart failure and mid-range (HFmrEF) or preserved ejection fraction (HFpEF) according to their left ventricular ejection fraction (LVEF) identifies differences in their exercise hemodynamic profile, and whether classification according to an index of right ventricular (RV) function improves differentiation. Patients with HFmrEF and HFpEF have hemodynamic compromise on exertion. The classification according to LVEF implies a key role of the left ventricle. However, RV involvement in exercise limitation is increasingly recognized. The tricuspid annular plane systolic excursion/systolic pulmonary arterial pressure (TAPSE/PASP) ratio is an index of RV and pulmonary vascular function. Whether exercise hemodynamics differ more between HFmrEF and HFpEF than between TAPSE/PASP tertiles is unknown. We analyzed 166 patients with HFpEF (LVEF ≥ 50%) or HFmrEF (LVEF 40-49%) who underwent basic diagnostics (laboratory testing, echocardiography at rest, and cardiopulmonary exercise testing [CPET]) and exercise with right heart catheterization. Hemodynamics were compared according to echocardiographic left ventricular or RV function. Exercise hemodynamics (e.g. pulmonary arterial wedge pressure/cardiac output [CO] slope, CO increase during exercise, and maximum total pulmonary resistance) showed no difference between HFpEF and HFmrEF, but significantly differed across TAPSE/PASP tertiles and were associated with CPET results. N-terminal pro-brain natriuretic peptide concentration also differed significantly across TAPSE/PASP tertiles but not between HFpEF and HFmrEF. In patients with HFpEF or HFmrEF, TAPSE/PASP emerged as a more appropriate stratification parameter than LVEF to predict clinically relevant impairment of exercise hemodynamics. Stratification of exercise hemodynamics in patients with HFpEF or HFmrEF according to LVEF or TAPSE/PASP, showing significant distinctions only with the RV-based strategy. All data are shown as median [upper limit of interquartile range] and were calculated using the independent-samples Mann-Whitney U test or Kruskal-Wallis test. PVR pulmonary vascular resistance; max maximum level during exercise.

Effects of mechanical ventilation with expiratory negative airway pressure on porcine pulmonary and systemic circulation: mechano-physiology and potential application

We studied the impact of mechanically regulated, expiratory negative airway pressure (ENAP) ventilation on pulmonary and systemic circulation including its mechanisms and potential applications. Microminipigs weighing about 10 kg were anesthetized (n = 5). First, hemodynamic variables were evaluated without and with ENAP to approximately −16 cmH2O. ENAP significantly increased heart rate and cardiac output, but decreased right atrial, pulmonary arterial and pulmonary capillary wedge pressures. Second, the evaluation was repeated following pharmacological adrenergic blockade, modestly blunting ENAP effects. Third, fluvoxamine (10 mg/kg) was intravenously administered to intentionally induce cardiovascular collapse in the presence of adrenergic blockade. ENAP was started when systolic pressure was < 40 mmHg in the animals assigned to ENAP treatment-group. Fluvoxamine induced cardiovascular collapse within 4 out of 5 animals. ENAP increased systolic pressure to > 50 mmHg (n = 2): both animals fully recovered without neurological deficit, whereas without ENAP both animals died of cardiac arrest (n = 2). ENAP may become an innovative treatment for drug-induced cardiovascular collapse.

Salutary Acute Effects of Exercise on Central Hemodynamics in Heart Failure With Preserved Ejection Fraction

BackgroundA warmup period of priming exercise has been shown to improve peripheral oxygen transport in older adults. We sought to determine the acute effects of priming exercise on central hemodynamics at rest and during a repeat exercise in heart failure with preserved ejection fraction (HFpEF). Methods and ResultsThis is a post hoc analysis from 3 studies. Patients with HFpEF (n = 42) underwent cardiac catheterization with simultaneous expired gas analysis at rest and during exercise (20 W for 5 minutes, priming exercise). Measurements were then repeated at rest and during a second bout of exercise at a 20-W workload (second exercise). During the priming exercise, patients with HFpEF displayed dramatic increases in biventricular filling pressures and exercise-induced pulmonary hypertension. After the priming exercise at rest, biventricular filling pressures and pulmonary artery (PA) pressures were lower and lung tidal volume was increased. During the second bout of exercise, biventricular filling (PA wedge pressure, 29 ± 8 mm Hg at second exercise vs 32 ± 7 mm Hg at first exercise, P = .0003) and PA pressures were lower, and PA compliance increased. ConclusionsThis study shows that short duration, submaximal priming exercise attenuates the pathologic increases in filling pressures, improving pulmonary vascular hemodynamics at rest and during repeat exercise in patients with HFpEF.

Impact of right ventricular work and pulmonary arterial compliance on peak exercise oxygen uptake in idiopathic pulmonary arterial hypertension

BackgroundPulmonary arterial hypertension (PAH) is associated with increased right ventricular (RV) afterload, RV dysfunction and decreased peak oxygen uptake (pVO2). However, the pulmonary hemodynamic mechanisms measured by exercise right heart catheterization (RHC) that contribute to reduced pVO2 in idiopathic PAH (IPAH) are not completely characterized. Therefore, we sought to evaluate the exercise RHC determinants of pVO2 in patients with IPAH. Methods519 consecutive patients with suspected and/or confirmed pulmonary hypertension were prospectively screened to identify 20 patients with IPAH. All IPAH patients were prospectively evaluated with resting and exercise RHC and cardiopulmonary exercise testing. Results85% of the patients were female; the median age was 34[29–42] years old. At peak exercise, mean pulmonary arterial (PA) pressure was 76 ± 17 mmHg, PA wedge pressure was 14 ± 5 mmHg, cardiac output (CO) was 5.7 ± 1.9 L/min, pulmonary vascular resistance was 959 ± 401 dynes/s/cm5 and PA compliance was 0.9[0.6–1.2] ml/mmHg. On univariate analysis, pVO2 positively correlated to peak CO, peak cardiac index, peak stroke volume index, peak RV stroke work index (RVSWI) and peak oxygen saturation. There was a negative correlation between pVO2 and Δ (rest to peak change) PA compliance. In age-adjusted multivariate model, peak RVSWI (Coefficient = 0.15, Beta = 0.63, 95% CI [0.07–0.22], p < 0.01) and ΔPA compliance (Coefficient = −2.51, Beta = −0.43, 95% CI [−4.34-(−0.68)], p = 0.01) had the best performance predicting pVO2 (R2 = 0.66). ConclusionsIn conclusion, a load dependent measurement of RV function (RVSWI) and the pulsatile component of RV afterload (ΔPA compliance) significantly influence pVO2 in IPAH, further highlighting the pivotal role of hemodynamic coupling to IPAH exercise capacity.

Acute Unloading Effects of Sildenafil Enhance Right Ventricular–Pulmonary Artery Coupling in Heart Failure

BackgroundPhosphodiesterase-5A inhibitors (PDE5i) are sometimes used in patients with advanced heart failure with reduced ejection fraction before heart transplant or left ventricular assist device implantation to decrease right ventricular (RV) afterload and mitigate the risk of right heart failure. Conflicting evidence exists regarding the impact of these drugs on RV contractility. The aim of this study was to explore the acute effects of PDE5i on ventricular–vascular coupling and load-independent RV contractility. MethodsTwenty-two patients underwent right heart catheterization and gated equilibrium blood pool single photon emission computed tomography, before and after 20 mg intravenous sildenafil. Single photon emission computed tomography and right heart catheterization-derived data were used to calculate RV loading and contractility. ResultsPDE5i induced a decrease in the right atrial pressure (–43%), pulmonary artery (PA) mean pressure (–26%), and PA wedge pressure (PAWP; –23%), with favorable reductions in pulmonary vascular resistance (–41%) and PA elastance (–40%), and increased cardiac output (+13%) (all P < 0.01). The RV ejection fraction increased with sildenafil (+20%), with no change of RV contractility (P = 0.74), indicating that the improvement in the RV ejection fraction was related to enhanced RV–PA coupling (r = 0.59, P = 0.004) by a decrease in the ventricular load. RV diastolic compliance increased with sildenafil. The decrease in the PAWP correlated with RV end-diastolic volume decrease; no relationship was observed with the change in LV transmural pressure, suggesting decreased pericardial constraint. ConclusionsAcute PDE5i administration has profound RV afterload-reducing effects, improves the RVEF, decreases RV volumes, and decreases the PAWP, predominantly through relief of pericardial constraint, without effects on RV chamber contractility. These findings support further study of PDE5i in protection of RV function in advanced heart failure with reduced ejection fraction who are at risk of RV failure.

Abstract 16412: The Predictors of Hemodynamic Response to Phosphodiesterase-5a Inhibition in Advanced HFrEF

Introduction: In advanced HFpEF, acute phosphodiesterase 5 (PDE5) inhibition leads to favorable change in pulmonary vascular resistance (PVR) and to an increased cardiac output (CO) of variable degree. The determinants of the response are poorely understood. Methods: 47 HFrEF patients (85% males, 57±11 years, NYHA 2.9±0.5, 55% non-ischemic, PAmean 42±8 mmHg, 43% RV dysfunction) underwent clinical exam, echocardiography, biochemical tests and right heart catheterization (RHC) before and after I.V. administration of sildenafil (20 mg). Baseline predictors of absolute and relative (%diff) change of PVR and CO were studied. Results: PDE5i led to highly significant (p&lt;0.001) reduction of pulmonary artery (PA) mean pressure (-11±9 mmHg), PVR (-2.2±1.6 WU;-42±24%), PA wedge pressure (-5.2±7.3 mmHg), CVP (-3.2±2.3 mmHg) and to increase in cardiac output (+0.6±0.7 l/min; +18±23%). PVR decreased more than systemic resistance (PVR/SVR -27±30%diff). Predictors of high CO response (COdiff%) were: low BMI, no diabetes, low baseline CO and severity of mitral or tricuspid regurgitation (r=0.53 or =0.43, both p&lt;0.003). The strongest predictor of high PVR%diff was plasma potassium level. HF etiology, renal function, gender, RAAS inhibitor dose, renin or aldosterone levels were unelated to pulmonary vasoreactivity. Patients who dropped PVR&lt;3 WU after PDE5i had higher plasma K+ (4.1±0.5 vs 4.5±0.3 mmol/L, p=0.01) than those who did not, similar relation was found for K+ and PDE5i-induced change of transpulmonary gradient. Conclusions: The largest increase in CO after PDE5i is observed in HFrEF patients with severe mitral (or tricuspid) regurgitation, probably due to chamber unloading and reduction of regurgitant SV. Pulmonary vasodilator response to PDE5i may be influenced by plasma potassium level. High-normal plasma potassium levels may preserve normal pulmonary vasoreactivity in HFrEF, perhaps by influencing K-channels in pulmonary vascular smooth muscle cells.

Abstract 17168: Myocardial Natriuretic Peptide Expression in Heart Failure With Preserved Ejection Fraction

Introduction: Serum natriuretic peptides (NP) are reduced in heart failure with preserved ejection fraction (HFpEF) compared to HFrEF; however, myocardial NP expression in HFpEF is unknown. We analyzed serum NTproBNP and myocardial RNAseq data to test the hypothesis that 1) lower myocardial NP expression in HFpEF drives the difference in serum levels, and 2) HFpEF with higher NP expression have transcriptomic signatures more similar to HFrEF. Methods: HFpEF patients (n=41) with clinical HF, LVEF≥50%, and meeting current consensus criteria for HFpEF underwent right heart catheterization and right ventricular (RV) endomyocardial biopsy. We performed differential gene expression analysis of RV septal tissue from HFpEF and compared to explanted HFrEF (n=30) and unused donor hearts (n=24, Control). Results: Myocardial NPPB expression was 5-fold higher in HFrEF vs Control (p&lt;0.001) and unchanged in HFpEF vs Control, while NPPA expression was 9-fold higher in HFrEF and 5-fold higher in HFpEF vs Control (p&lt;0.0001 for both comparisons). After adjustment for renal function and BMI, myocardial NPPB expression was significantly associated with serum NTproBNP in HFpEF (R 2 0.68; p&lt;0.0001 for renal function, NPPB expression; p=0.03 for BMI). Pulmonary artery (PA) systolic pressure and PA wedge pressure correlated with myocardial NPPB expression (PASP R 2 0.45, p&lt;0.0001; PAWP R 2 0.25, p=0.01), even after adjustment for comorbidities. HFpEF patients with high (≥ median NPPB expression in HFpEF) vs low NPPB expression had transcriptomic signatures more similar to HFrEF using ~13,000 genes in a Principal Component Analysis (Figure), quantified by vector distance from HFrEF (p=0.017). Conclusions: HFpEF patients have reduced serum NTproBNP due to lower myocardial NPPB gene expression. HFpEF patients with higher NPPB expression have transcriptomic signatures more similar to HFrEF, highlighting a HFpEF subgroup that may benefit from targeted therapies.