Time Of Right Heart Catheterization Research Articles

Characteristic disease defects in circulating endothelial cells isolated from patients with pulmonary arterial hypertension.

Pulmonary arterial hypertension (PAH) is a progressive disease characterized by elevated pulmonary arterial pressures that can lead to right heart failure and death. No cure exists for this disease, but therapeutic advancements have extended its median survival from 2 to 7 years. Mechanistic research in PAH has been limited by factors including that a) animal models do not fully recapitulate the disease or provide insights into its pathogenesis, and b) cellular material from PAH patients is primarily obtained from donor lungs during autopsy or transplantation, which reflect end-stage disease. Therefore, there is a need to identify tools that can elucidate the specific mechanisms of human disease in individual patients, a critical step to guide treatment decisions based on specific pathway abnormalities. Here we demonstrate a simple method to isolate and culture circulating endothelial cells (CECs) obtained at the time of right heart catheterization in PAH patients. We tested these CECs using transcriptomics and found that they have typical traits of PAH, including those involving key treatment pathways, i.e. nitric oxide, endothelin, prostacyclin and BMP/activin pathways. CECs show important gene expression changes in other central PAH disease pathways. In summary, we present a new cellular model for the ex-vivo mechanistic evaluation of critical PAH pathways that participate in the pathogenesis of the disease and may help personalized therapeutic decisions.

Nitroprusside Combined with Leg Raise at the Time of Right Heart Catheterization to Differentiate Precapillary from Other Hemodynamic Forms of Pulmonary Hypertension: A Single-Center Pilot Study.

Pulmonary hypertension (PH) can arise from several distinct disease processes, with a percentage presenting with combined pre- and postcapillary pulmonary hypertension (cpcPH). Patients with cpcPH are unsuitable candidates for PH-directed therapies due to elevated pulmonary capillary wedge pressures (PCWPs); however, the PCWP is dynamic and is affected by both preload and afterload. Many patients that are diagnosed with cpcPH are hypertensive at the time of right heart catheterization which has the potential to increase the PCWP and, therefore, mimic a more postcapillary-predominant phenotype. In this small pilot study, we examine the effect of nitroprusside combined with dynamic preload augmentation with a passive leg raise maneuver in hypertensive cpcPH patients at the time of right heart catheterization to identify a more precapillary-dominant PH phenotype. Patients that met the criteria of PCWP ≤ 15 mmHg with nitroprusside infusion and PCWP ≤ 18 mmHg with nitroprusside infusion and simultaneous leg raise were started on pulmonary vascular-targeted therapy. Long-term PH therapy was well tolerated, with increased six-minute walk distance, improved WHO functional class, decreased NT-proBNP, and improved REVEAL 2.0 Lite Risk Score in this precapillary-dominant PH phenotype. This small study highlights the importance of characterizing patient physiology beyond resting conditions at the time of right heart catheterization.

Abstract 14483: Myeloid Cell Derived IL1b Contributes to Pulmonary Vascular Remodeling in Heart Failure With Preserved Ejection Fraction

Introduction: Pulmonary hypertension (PH) in heart failure with preserved ejection fraction (HFpEF) is a common and highly morbid syndrome, but mechanisms driving PH-HFpEF are poorly understood. Hypothesis: We sought to determine whether a well-accepted murine model of HFpEF also displays features of PH, and we sought to identify pathways that might drive early remodeling of the pulmonary vasculature in HFpEF. . Methods: Eight-week-old male and female C57BL/6J mice received either L-NAME and high fat diet (HFD) or control water and diet for 2, 5, and 12 weeks. Db/db mice were studied as a second model of HFpEF. Early pathways regulating PH were identified by bulk and single cell RNA sequencing. Findings were confirmed by immunostain in lungs of mice or lung slides from clinically performed autopsies of PH-HFpEF patients. ELISA was used to verify IL1β in mouse lung, mouse plasma, and also human plasma from PH-HFpEF patients obtained at the time of right heart catheterization. Clodronate liposomes and an anti-IL1β antibody were utilized to deplete macrophages and IL1β, respectively, to assess their impact on pulmonary vascular remodeling in HFpEF in mouse models. Results: L-NAME/HFD treated mice developed PH, small vessel muscularization, and right heart dysfunction. Inflammation-related gene ontologies were over-represented in bulk RNA sequencing analysis of whole lungs, with an increase in CD68 + cells in both murine and human PH-HFpEF lungs. Cytokine profiling showed an increase in IL1β in mouse and human plasma. Finally, clodronate liposome treatment in mice prevented PH in L-NAME/HFD treated mice, and IL1β depletion also attenuated PH in L-NAME/HFD treated mice. Conclusions: We report a novel model for the study of PH and right heart remodeling in HFpEF, and we identify myeloid cell derived IL1β as an important contributor to PH in HFpEF.

Myeloid Cell Derived IL1β Contributes to Pulmonary Hypertension in HFpEF.

Pulmonary hypertension (PH) in heart failure with preserved ejection fraction (HFpEF) is a common and highly morbid syndrome, but mechanisms driving PH-HFpEF are poorly understood. We sought to determine whether a well-accepted murine model of HFpEF also displays features of PH, and we sought to identify pathways that might drive early remodeling of the pulmonary vasculature in HFpEF. Eight-week-old male and female C57BL/6J mice received either Nγ-nitro-L-arginine methyl ester and high-fat diet or control water and diet for 2, 5, and 12 weeks. The db/db mice were studied as a second model of HFpEF. Early pathways regulating PH were identified by bulk and single-cell RNA sequencing. Findings were confirmed by immunostain in lungs of mice or lung slides from clinically performed autopsies of patients with PH-HFpEF. ELISA was used to verify IL-1β (interleukin-1 beta) in mouse lung, mouse plasma, and also human plasma from patients with PH-HFpEF obtained at the time of right heart catheterization. Clodronate liposomes and an anti-IL-1β antibody were utilized to deplete macrophages and IL-1β, respectively, to assess their impact on pulmonary vascular remodeling in HFpEF in mouse models. Nγ-nitro-L-arginine methyl ester/high-fat diet-treated mice developed PH, small vessel muscularization, and right heart dysfunction. Inflammation-related gene ontologies were overrepresented in bulk RNA sequencing analysis of whole lungs, with an increase in CD68+ cells in both murine and human PH-HFpEF lungs. Cytokine profiling showed an increase in IL-1β in mouse and human plasma. Finally, clodronate liposome treatment in mice prevented PH in Nγ-nitro-L-arginine methyl ester/high-fat diet-treated mice, and IL-1β depletion also attenuated PH in Nγ-nitro-L-arginine methyl ester/high-fat diet-treated mice. We report a novel model for the study of PH and right heart remodeling in HFpEF, and we identify myeloid cell-derived IL-1β as an important contributor to PH in HFpEF.

Prospective Evaluation of Venous Excess Ultrasound for Estimation of Venous Congestion

Venous excess ultrasound (VExUS) is a novel ultrasound technique previously reported as a noninvasive measure of venous congestion and predictor of cardiorenal acute kidney injury. Are there associations between VExUS grade and cardiac pressures measured by right heart catheterization (RHC) and cardiac biomarkers and clinical outcomes in patients undergoing RHC? We conducted a prospective cohort study at the Denver Health Medical Center from December 20, 2022, to March 25, 2023. All patients undergoing RHC underwent a blinded VExUS assessment prior to their procedure. Multivariable regressions were conducted to assess relationships between VExUS grade and cardiac pressures, biomarkers, and changes in weight among patients with heart failure, a proxy for diuretic success. Receiver operating characteristic curve and area under the curve (AUC) were derived for VExUS, inferior vena cava (IVC) diameter, and IVC collapsibility index (ICI) to predict right atrial pressure (RAP) > 10 and< 7mmHg. Among 81 patients, 45 of whom were inpatients, after adjusting for age, sex, and Charlson Comorbidity Index, there were significant relationships between VexUS grade of 2 (β= 4.8; 95% CI, 2.6-7.1; P< .01) and 3 (β= 11; 95% CI, 8.9-14; P< .01) and RAP, VExUS grade of 2 (β= 6.8; 95% CI, 0.16-13; P= .045) and 3 (β= 15; 95% CI, 7.3-22; P< .01) and mean pulmonary artery pressure, and VExUS grade of 2 (β= 7.0; 95% CI, 3.9-10; P< .01) and 3 (β= 13; 95% CI, 9.5-17; P< .01) and pulmonary capillary wedge pressure. AUC values for VExUS, IVC diameter, and ICI as predictors of RAP > 10mmHg were 0.9 (95%CI, 0.83-0.97), 0.77 (95%CI, 0.68-0.88), and 0.65 (95%CI, 0.52-0.78), respectively. AUC values for VExUS, IVC diameter, and ICI as predictors of RAP< 7mmHg were 0.79 (95%CI, 0.70-0.87), 0.74 (95%CI, 0.64-0.84), and 0.62 (95%CI, 0.49-0.76), respectively. In a subset of 23 patients with heart failure undergoing diuresis, there was a significant association between VExUS grade 3 and change in weight between time of RHC and discharge (P= .025). Although more research is required, VExUS has the potential to increase diagnostic and therapeutic capabilities of physicians at the bedside and increase our understanding of the underappreciated problem of venous congestion.

Variation in Hemodynamic Assessment and Interpretation: A Call to Standardize the Right Heart Catheterization

BackgroundInvasive hemodynamic measurement via right heart catheterization has shown divergent data in its role in the treatment of patients with heart failure (HF) and cardiogenic shock. We hypothesized that variation in data acquisition technique and interpretation might contribute to these observations. We sought to assess differences in hemodynamic acquisition and interpretation by operator subspecialty as well as level of experience. Methods and ResultsIndividual-level responses to how physicians both collect and interpret hemodynamic data at the time of right heart catheterization was solicited via a survey distributed to international professional societies in HF and interventional cardiology. Data were stratified both by operator subspecialty (HF specialists or interventional cardiologists [IC]) and operator experience (early career [≤10 years from training] or late career [>10 years from training]) to determine variations in clinical practice. For the sensitivity analysis, we also look at differences in each subgroup. A total of 261 responses were received. There were 141 clinicians (52%) who self-identified as HF specialists, 99 (38%) identified as IC, and 20 (8%) identified as other. There were 142 early career providers (54%) and late career providers (119 [46%]). When recording hemodynamic values, there was considerable variation in practice patterns, regardless of subspecialty or level of experience for the majority of the intracardiac variables. There was no agreement or mild agreement among HF and IC as to when to record right atrial pressures or pulmonary capillary wedge pressures. HF cardiologists were more likely to routinely measure both Fick and thermodilution cardiac output compared with IC (51% vs 29%, P < .001), something mirrored in early career vs later career cardiologists. ConclusionsSignificant variation exists between the acquisition and interpretation of right heart catheterization measurements between HF and IC, as well as those early and late in their careers. With the growth of the heart team approach to management of patients in cardiogenic shock, standardization of both assessment and management practices is needed.

COUNTERPOINT: Pulmonary Vascular Resistance 2.0— Shedding Light or Casting Shadows?

COUNTERPOINT: Pulmonary Vascular Resistance 2.0— Shedding Light or Casting Shadows?

Predictive Accuracy of Hemodynamic Surrogate Indices in Patients with Advanced Heart Failure

<h3>Purpose</h3> Right heart catheterization (RHC) is an essential tool in the evaluation advanced heart failure (AHF) patients. It is unclear which of the established hemodynamic surrogate indices are most predictive of poor outcomes. We aimed to compare the predictive accuracy of published hemodynamic surrogates in AHF patients. <h3>Methods</h3> In a pooled registry of patients undergoing RHC for evaluation of decompensated heart failure, we analyzed several hemodynamic indices with cut-off values taken from previously published studies, including: systolic blood pressure / pulmonary capillary wedge pressure (SBP/PCWP) ratio < 4; cardiac power index (CPI=MAP x CI/451) <0.44; cardiac power efficiency (CPE= CPI/PCWP) <0.018; aortic pulsatility index (API=SBP-DBP/PCWP) <1.45; pulmonary artery pulsatility index (PAPi=PASP-PADP/CVP) <2.0; CVP + PCWP >30; CVP/PCWP >0.6. The primary composite outcome was defined as freedom from advanced heart failure therapies, inotropes, or death. <h3>Results</h3> A total of 182 patients (median age 59, 71% male) were included and were on oral medical therapy at the time of RHC. The median (mmHg) SBP was 113 (101, 122), MAP 86 (76.3, 94), RA 15 (10, 18), mean PA 39.5 (32, 47.6), PCWP 26 (20, 32), cardiac index 1.8 (L/m/m2) (1.5, 2.1). At 30 days, 122 patients met the primary composite outcome including 5 deaths. At end of study follow up (up to 365 days) 15 additional patients (n=137) met the primary outcome. All hemodynamic surrogates at their designated cut-off values were associated with an increased risk of the primary outcome at 30 days (<i>P</i><0.05), and at follow-up up to one year with the exception of API (Figure). The receiver operator characteristic analyses for all indices at their pre-designated cut-off values had a comparable range of risk discrimination of 0.58 to 0.64 (Figure) at one-year. <h3>Conclusion</h3> Novel hemodynamic surrogates may be additive in risk prognostication of AHF patients, but can vary in diagnostic accuracy at their pre-specified cut-off values when applied to external clinical cohorts.

Treatment with neurohormonal inhibitors and prognostic outcome in pulmonary arterial hypertension with risk factors for left heart disease.

BACKGROUNDDespite major advances in pharmacologic treatment, patients with pulmonary arterial hypertension (PAH) still have a considerably reduced life expectancy. In this context, chronic hyperactivity of the neurohormonal axis has been shown to be detrimental in PAH, thus providing novel insights on the role of neurohormonal blockade as a potential therapeutic target.AIMTo evaluate the application and prognostic effect of neurohormonal inhibitors (NEUi) in a single-center sample of patients with idiopathic PAH and risk factors for left heart disease.METHODSWe analyzed data retrospectively collected from our register of right heart catheterizations performed consecutively from January 1, 2005 to October 31, 2018. Patients on beta-blocker, angiotensin-converting enzyme inhibitor, angiotensin receptor blocker or mineralocorticoid receptor antagonist at the time of right heart catheterization were classified as NEUi users and compared to NEUi non-recipients.RESULTSComplete data were available for 57 PAH subjects: 27 of those (47.4%) were taking at least one NEUi at the time of right heart catheterization and were compared with the remaining 36 NEUi non-recipients. NEUi users were older and had a higher cardiovascular risk profile compared to non-recipients. Additionally, NEUi non-users had a higher probability of dying during the course of follow-up than NEUi recipients (56.7% vs 25.9%, log-rank P = 0.020).CONCLUSIONThe above data highlighted a subgroup of patients with PAH and comorbidities for left heart disease in which NEUi use has shown to be associated with improved survival. Future prospective studies are needed to identify the most appropriate therapeutic strategies in this subset population.

THE ROLE OF PROVOCATIVE TESTING DURING HEMODYNAMIC ASSESSMENT TO IMPROVE PULMONARY HYPERTENSION DIAGNOSIS IN OLDER ADULTS

BACKGROUND Pulmonary Hypertension (PH) complicates cardiac and respiratory diseases. Hemodynamic classification of PH broadly defines 2 subsets: pulmonary arterial hypertension (PAH) and PH of left heart disease (PH-LHD). In older patients, particularly with cardiovascular risk factors, clinical and hemodynamic characteristics of PAH and PH-LHD overlap. Thus clinicians face a therapeutic dilemma; PAH therapy may be underutilized in PAH patients to avoid inadvertent administration to PH-LHD patients. Our goal was to evaluate the utility of right heart catheterization(RHC) with exercise to support clinical decisions regarding use of PAH therapy in older adults suspected of having PH with risk factors for PH-LHD. METHODS AND RESULTS Retrospective cohort study of patients referred by a PH program for RHC with exercise to evaluate suspected or confirmed PH, between 2017-2020. Consecutive patients >50 years and at least 1 cardiovascular risk factor (BMI>30kg/m2, HTN, diabetes, hypercholesterolemia, ischemic heart disease, atrial fibrillation(AF)) were included. Primary outcome: use of PAH therapy at the time of RHC and in follow-up. Secondary outcomes: patient reported quality of life (QOL) at time of RHC and in follow-up, using SF36 assay. 61 patients were included in our study, mean age:69±10 years, 56% women. Over 90% patients has 2 or more risk factors for PH-LHD, 34% had a history of AF. At time of RHC, although more than 30% were known to have PH, PAH therapy was prescribed to 20% of patients; phosphodiesterase type 5 inhibitors (PDE5i) n=9, endothelin antagonists (ETA) n=1, and dual therapy (PDE5i+ETA) n=1. Baseline RHC demonstrated no PH in 22 patients (36%) and PH in 39 (64%): 27 with PAH, and 12 with PH-LHD. After exercise RHC, 14 (23%) had no PH, 44 were diagnosed with PH:16 with PAH and 28 with PH-LHD. In follow-up, the proportion of cohort treated with PAH therapy increased to 28%, mostly patients confirmed to have PAH at rest and exercise. PAH therapy included single PDE5i (8 patients), single ETA (5 patients), or combination therapy (with 2 or more PAH medications, 4 patients). Improvement in the physical functioning (median 10, IQR 23.8) and overall health (median 25, IQR 43.8) aspects of QOL were seen at 1 year follow-up. CONCLUSION Among patients with suspected or confirmed PH, and high burden of cardiovascular risk factors, use of PAH therapies is low. Exercise RHC increased the proportion of patients diagnosed with PH and shifted the classification in a proportion from PAH to PH-LHD. QOL improved as well. Pulmonary Hypertension (PH) complicates cardiac and respiratory diseases. Hemodynamic classification of PH broadly defines 2 subsets: pulmonary arterial hypertension (PAH) and PH of left heart disease (PH-LHD). In older patients, particularly with cardiovascular risk factors, clinical and hemodynamic characteristics of PAH and PH-LHD overlap. Thus clinicians face a therapeutic dilemma; PAH therapy may be underutilized in PAH patients to avoid inadvertent administration to PH-LHD patients. Our goal was to evaluate the utility of right heart catheterization(RHC) with exercise to support clinical decisions regarding use of PAH therapy in older adults suspected of having PH with risk factors for PH-LHD. Retrospective cohort study of patients referred by a PH program for RHC with exercise to evaluate suspected or confirmed PH, between 2017-2020. Consecutive patients >50 years and at least 1 cardiovascular risk factor (BMI>30kg/m2, HTN, diabetes, hypercholesterolemia, ischemic heart disease, atrial fibrillation(AF)) were included. Primary outcome: use of PAH therapy at the time of RHC and in follow-up. Secondary outcomes: patient reported quality of life (QOL) at time of RHC and in follow-up, using SF36 assay. 61 patients were included in our study, mean age:69±10 years, 56% women. Over 90% patients has 2 or more risk factors for PH-LHD, 34% had a history of AF. At time of RHC, although more than 30% were known to have PH, PAH therapy was prescribed to 20% of patients; phosphodiesterase type 5 inhibitors (PDE5i) n=9, endothelin antagonists (ETA) n=1, and dual therapy (PDE5i+ETA) n=1. Baseline RHC demonstrated no PH in 22 patients (36%) and PH in 39 (64%): 27 with PAH, and 12 with PH-LHD. After exercise RHC, 14 (23%) had no PH, 44 were diagnosed with PH:16 with PAH and 28 with PH-LHD. In follow-up, the proportion of cohort treated with PAH therapy increased to 28%, mostly patients confirmed to have PAH at rest and exercise. PAH therapy included single PDE5i (8 patients), single ETA (5 patients), or combination therapy (with 2 or more PAH medications, 4 patients). Improvement in the physical functioning (median 10, IQR 23.8) and overall health (median 25, IQR 43.8) aspects of QOL were seen at 1 year follow-up. Among patients with suspected or confirmed PH, and high burden of cardiovascular risk factors, use of PAH therapies is low. Exercise RHC increased the proportion of patients diagnosed with PH and shifted the classification in a proportion from PAH to PH-LHD. QOL improved as well.

Haemodynamic parameters associated with renal function prior to and following heart transplantation.

AimsAbnormal renal function is a common feature in patients on heart transplant waiting lists. This study aimed to identify the haemodynamic parameters associated with decreased estimated glomerular filtration rate (eGFR) in patients listed for heart transplantation (HT) and renal function improvement following HT.Methods and resultsA total of 176 adults (52 years old, 81% men) with available right heart catheterization (RHC) listed in our centre for HT between 2014 and 2019 were studied. Cardiac catheterization measurements were obtained at time of HT listing evaluation. Changes in renal function were assessed between RHC and 6 months after HT. Median eGFR was 63 mL/min/1.73 m2 at time of RHC. Central venous pressure > 10 mmHg was associated with a two‐fold increase in the likelihood of eGFR < 60 mL/min/1.73 m2 at time of RHC (adjusted odd ratio, 2.2; 95% confidence interval, 1.1–4.7; P = 0.04). In the 134 patients (76%) who underwent HT during follow‐up, eGFR decreased by 7.9 ± 29.7 mL/min/1.73 m2 from RHC to 6 months after HT. In these patients, low cardiac index (<2.1 L/min/m2) at initial RHC was associated with a (adjusted) 6 month post‐HT eGFR improvement of 12.2 mL/min/1.73 m2 (P = 0.018). Patients with eGFR < 60 mL/min/1.73 m2 and low cardiac index at time of RHC exhibited the greatest eGFR improvement (delta eGFR = 18.3 mL/min/1.73 m2) while patients with eGFR ≥ 60 mL/min/1.73 m2 and normal cardiac index had a marked decrease in eGFR (delta eGFR = −27.7 mL/min/1.73 m2, P < 0.001).ConclusionsCentral venous pressure is the main haemodynamic parameter associated with eGFR < 60 mL/min/1.73 m2 in patients listed for HT. Low cardiac index prior to HT is associated with post‐transplant renal function recovery.

Combined Utility of Aortic Pulsatility Index and Pulmonary Artery Pulsatility Index for Risk Stratification in Advanced Heart Failure Patients

<h3>Purpose</h3> To assess the prognostic role of simultaneous biventricular function using hemodynamic parameters in advanced heart failure patients. <h3>Methods</h3> We retrospectively analyzed 184 patients undergoing a milrinone drug study at time of right heart catheterization (RHC) at our institution from January 2013 to January 2019. Aortic pulsatility index (API) was calculated as (systolic blood pressure - diastolic blood pressure)/pulmonary capillary wedge pressure, and pulmonary artery pulsatility index (PAPI) was calculated as (systolic pulmonary artery pressure - diastolic pulmonary artery pressure)/central venous pressure. Using our team's previous identification of cutpoint values for API and PAPI, 1.45 and 2.3, respectively, we stratified patients into the following groups: (1) High API, High PAPI; (2) High API, Low PAPI; (3) Low API, High PAPI; and (4) Low API, Low PAPI. Univariate and multivariate logistic regression analyses were performed to determine association with escalation of therapy, defined as left ventricular assist device implantation, heart transplantation, or death. <h3>Results</h3> Low API, Low PAPI was associated with escalation of therapy or death at 30-days (OR 3.2, 95% CI 1.23 - 9.49, p = 0.024). Low API, Low PAPI and Low API, High PAPI were also associated with the one-year endpoint of freedom from escalation of therapy or death (OR 3.63, 95% CI 1.55 - 8.75, p = 0.003; OR 4.13, 95% CI 1.5 - 12.45, p = 0.008; respectively). In multivariate analysis, both of these risk statuses remained significant predictors of the one-year endpoint when adjusting for Fick cardiac index (OR 3.72, 95% CI 1.5 - 9.48, p = 0.005; OR 4.18, 95% CI 1.49 - 12.82, p = 0.009; respectively). <h3>Conclusion</h3> The combined use of API and PAPI possesses utility for risk stratification regarding both short- and long-term freedom from escalation of therapy or death.

Right ventricular load and contractility in HIV-associated pulmonary hypertension.

BackgroundPeople living with human immunodeficiency virus (PLWH) are at risk of developing pulmonary hypertension (PH) and right ventricular (RV) dysfunction, but understanding of the relationship of RV function to afterload (RV-PA coupling) is limited. We evaluated the clinical and hemodynamic characteristics of human immunodeficiency virus (HIV)-associated PH.MethodsWe performed a retrospective review of patients with a diagnosis of HIV undergoing right heart catheterization (RHC) from 2000–2016 in a tertiary care center. Inclusion criteria were diagnosis of HIV, age ≥ 18 years and availability of RHC data. PH was classified as either pulmonary arterial hypertension (PAH; mean pulmonary arterial pressure [mPAP] ≥ 25mmHg with pulmonary artery wedge pressure [PAWP] ≤ 15mmHg) or pulmonary venous hypertension (PVH; mPAP ≥ 25mmHg with PAWP > 15). We collected demographics, CD4 cell count, HIV viral load, RHC and echocardiographic data. The single beat method was used to calculate RV-PA coupling from RHC.ResultsSixty-two PLWH with a clinical likelihood for PH underwent RHC. Thirty-two (52%) met PH criteria (15 with PAH, 17 with PVH). Average time from diagnosis of HIV to diagnosis of PH was 11 years. Eleven of 15 individuals with PAH were on antiretroviral therapy (ART) while all 17 patients with PVH were on ART. Compared to PLWH without PH, those with PH had an increased likelihood of having a detectable HIV viral load and lower CD4 cell counts. PLWH with PAH or PVH had increased RV afterload with normal RV contractility, and preserved RV-PA coupling.ConclusionPLWH with PH (PAH or PVH) were more likely to have a detectable HIV viral load and lower CD4 count at the time of RHC. PLWH with PAH or PVH had increased RV afterload, normal RV contractility, with preserved RV-PA coupling suggestive of an early onset, mild, and compensated form of PH. These results should be confirmed in larger studies.

Exercise right ventricular ejection fraction predicts right ventricular contractile reserve

Right ventricular (RV) contractile reserve shows promise as an indicator of occult RV dysfunction in pulmonary vascular disease. We investigated which measure of RV contractile reserve during exercise best predicts occult RV dysfunction and clinical outcomes. We prospectively studied RV contractile reserve in 35 human subjects referred for right heart catheterization for known or suspected pulmonary hypertension. All underwent cardiac magnetic resonance imaging, echocardiography, and supine invasive cardiopulmonary exercise testing with concomitant RV pressure-volume catheterization. Event-free survival was prospectively adjudicated from time of right heart catheterization for a 4-year follow-up period. RV contractile reserve during exercise, as measured by a positive change in end-systolic elastance (Ees) during exertion, was associated with elevation in pulmonary pressures but preservation of RV volumes. Lack of RV reserve, on the other hand, was tightly coupled with acute RV dilation during exertion (R2 = 0.76, p< 0.001). RV Ees and dilation changes each predicted resting RV-PA dysfunction. RV ejection fraction during exercise, which captured exertional changes in both RV Ees and RV dilation, proved to be a robust surrogate for RV contractile reserve. Reduced exercise RV ejection fraction best predicted occult RV dysfunction among a variety of resting and exercise RV measures, and was also associated with clinical worsening. RV ejection fraction during exercise, as an index of RV contractile reserve, allows for excellent identification of occult RV dysfunction, more so than resting measures of RV function, and may predict clinical outcomes as well.

Echocardiographic assessment of pulmonary arterial capacitance predicts mortality in pulmonary hypertension

BackgroundPulmonary arterial capacitance (PAC) is one of the strongest predictors of clinical outcomes in patients with pulmonary hypertension (PH). We examined the value of an echocardiographic surrogate for PAC (ePAC) as a predictor of mortality in patients with PH. MethodsWe performed a retrospective study of 302 patients with PH managed at a PH comprehensive care center over a cumulative follow-up time of 858 patient-years. Charts from 2004 to 2018 were reviewed to identify patients in whom a right heart catheterization (RHC) was performed within two months of an echocardiogram. Standard invasive, non-invasive, functional, and biochemical prognostic markers were extracted from the time of RHC. The primary outcome was all-cause mortality. Cox proportional hazards models were used to model the time from RHC to the primary outcome or last medical contact. ResultsVariables associated with all-cause mortality included ePAC [standardized hazard ratio (HR) 0.68, 95% CI 0.48−0.98, p = 0.036], RHC-PAC (HR 0.68, 95% CI 0.48−0.96, p = 0.027), echocardiographic pulmonary vascular resistance (HR 1.29, 95% CI 1.05–1.60, p = 0.017), six-minute walk distance (HR 0.43, 95% CI 0.23−0.82, p = 0.01), and B-type natriuretic peptide (HR 1.29, 95% CI 1.03–1.62, p = 0.027). In multivariable-adjusted Cox analysis, ePAC predicted all-cause mortality independently of age, gender, and multiple comorbidities. There was a graded and stepwise association between low (<0.15 cm/mmHg), medium (0.15−0.25 cm/mmHg), and high (>0.25 cm/mmHg) tertiles of ePAC and all-cause mortality. ConclusionsWe have demonstrated that ePAC is a readily available echocardiographic marker that independently predicts mortality in PH, and have provided clinically relevant ranges by which to risk-stratify patients and predict mortality.

Risk of Liver Dysfunction After Left Ventricular Assist Device Implantation

Incident liver dysfunction after left ventricular assist device implantation has been previously associated with adverse outcomes, yet data on perioperative risk markers are sparse. We retrospectively reviewed consecutive patients undergoing continuous-flow left ventricular assist device implant between 2007 and 2017 at a single institution. Perioperative variables were evaluated by univariate modeling and adjusted for false discovery rate. Variables most significantly associated with incident Interagency Registry for Mechanically Assisted Circulatory Support-defined liver dysfunction (INT-LD) were evaluated using logistic regression and optimal cutpoints were defined. One-year survival was evaluated using Kaplan-Meier analysis. We included 359 patients (79% male; mean age 59 ± 13 years; 46% ischemic; 64% destination therapy). Lower right ventricular stroke work index at the time of right heart catheterization, higher right atrial pressure 6 hours after right heart catheterization, higher preoperative total bilirubin, longer cardiopulmonary bypass time, and greater volume of intraoperative ultrafiltration were most strongly associated with incident INT-LD (adjusted P < .01 for each). Initial right ventricular stroke work index less than 460 mm Hg∗mL/m2 (odds ratio [OR] 4.6; 95% confidence interval [CI], 2.3 to 9.4), 6-hour right heart catheterization 14 mm Hg or greater (OR 4.3; 95% CI, 2.1 to 8.8), cardiopulmonary bypass time longer than 137 minutes (OR 3.3; 95% CI, 1.8 to 6.2; P < .01 for all), ultrafiltration more than 2.95 L (OR 3.7; 95% CI, 2 to 6.8), and total bilirubin greater than 1.4 mg/dL (OR 2.7; 95% CI, 1.4 to 5) were each strongly associated with risk of INT-LD, which was associated with decreased unadjusted 1-year survival (P < .001). Right ventricular stroke work index, right heart catheterization, cardiopulmonary bypass time, and ultrafiltration were each more strongly associated with elevated risk of INT-LD after left ventricular assist device implant than total bilirubin. Therefore, optimization of right ventricular hemodynamics and minimizing cardiopulmonary bypass time and ultrafiltration could potentially reduce the risk of liver dysfunction, but these observations require prospective validation.

Non-invasive Assessment of Pulmonary Hypertension Using a Small Portable Device Measuring Cardiac Intervals: Design for Telemonitoring

Background Pulmonary hypertension is a condition that pulmonary artery pressure iselevated. The diagnosis and monitoring of pulmonary artery pressure oftenrequiring invasive procedures. HEMOTAG, is a small portable device that usesmicro-sensors to capture cardiac vibrations and electrocardiogram, transducedvia thoracic electrodes. It is a viable option to measure cardiac timeintervals (CTIs), surrogate markers of intracardiac pressure. In this study,mitral valve closure (MVC) and isovolumetric contraction time (IVCT) wereassessed as valid markers for pulmonary artery pressure, compared againstintracardiac pressures measured simultaneously at the time of right heartcatheterization. Methods In 37 patients, mean pulmonary artery pressure (mPAP) was measured duringcardiac catheterization. Simultaneously, Hemotag analyzed CTIs: MVC and IVCT.The predictability value of non-invasively HEMOTAG-derived CTIs- MVC and IVCT -were assessed to determine elevated mPAP. Linear correlation analysisbetween CTIs and mPAP was performed. Sensitivity, specificity, positive, andnegative predictive values were calculated. Results Mean age was 65.40 ± 12.42years, mean ejection fraction was 54.61 ± 14.24%,48% were women, 55.2% had left valvular disease, 27.6% had systolicdysfunction, and mean mPAP was 16.10 ± 5.40 mmHg. With a paired dichotomous interpretation,sensitivity of 81% was noted for MVC and specificity of 100% was observed withIVCT. A receiver operator characteristic curve was employed to assessperformance with an AUC of 0.71 and 0.64 for MVC and IVCT, respectively. Therewere no strong correlations observed between mPAP and CTIs (Table 1). Conclusions HEMOTAG detected elevated mPAPwith good sensitivity and high specificity. This preliminary study hasdemonstrated the feasibility of estimating mPAP using a portable, non-invasivedevice that empowers patients to transmit such data from home instantaneouslyto providers. Further studies are required to validate HEMOTAG as apoint-of-care non-invasive assessment for pulmonary hypertension patients.

Cardiac Reserve as Assessed by Augmentation in Cardiac Power Efficiency Predicts Response to Intravascular Ventricular Assist System Support

The intravascular ventricular assist system (iVAS) is a durable, ambulatory counterpulsation device that is currently under investigation for advanced heart failure patients. Baseline cardiac power efficiency (CPE) has previously been reported to predict hemodynamic success after iVAS. We investigated the role of change in CPE after inotropic challenge, a marker of cardiac reserve, as a prognostic tool prior to iVAS support. Hemodynamic data at the time of right heart catheterization was collected on patients just prior to iVAS implantation. A subset of patients underwent milrinone loading followed by repeat hemodynamic assessment 10 min after a 50 mcg/kg milrinone infusion. Cardiac power index (CPI) was calculated as [CPI = cardiac index (CI) x mean arterial pressure (MAP)/451)] and CPE was calculated as [CPE = CPI/Pulmonary capillary wedge pressure (PCWP)]. CPE at baseline and after inotropic challenge was calculated and a percent augmentation of 25% or greater in CPE was used as a cutoff indicative of cardiac reserve. The combined endpoint of independently adjudicated heart failure events, dependency on inotropes 7 days after implant, need for escalation to ECMO or death was evaluated. 40 patients from a single institution underwent iVAS implantation. 39 patients underwent RHC prior to iVAS (11.7 +/- 14.0 days before surgery). 11 patients underwent milrinone loading followed by repeat hemodynamic assessment. Baseline hemodynamics revealed an average CPE of 0.0227 +/- 0.0148 watts*mmHg/m2 for the entire cohort. In the subset of patients who underwent milrinone loading, CPE increased on average 41% from 0.0141 +/- 0.0055 watts*mmHg/m2 to 0.0236 +/- 0.0114 watts*mmHg/m2 (p = 0.003). There was a trend towards freedom from death, ECMO, HF events, or inotrope dependency in those who were able to augment CPE by more than 25% (N = 8), compared to those with less (N = 3) cardiac reserve OR = 0.071 (95% CI 0.003 - 1.73, p = 0.105). Cardiac reserve as defined as a greater than 25% augmentation in CPE after milrinone challenge may predict future success with counterpulsation with iVAS. This hypothesis generating question warrants further investigation.

Outcomes Associated with Complete versus Partial LV Unloading in Patients with LVAD

Purpose LVAD implantation improves survival in end-stage heart failure (HF) patients. It is unclear at this time whether the goal of partial or complete left ventricle (LV) unloading is the best long-term strategy to maintain favorable outcomes especially when it relates to patients who received LVAD as destination therapy. Methods We conducted a retrospective analysis of end-stage HF patients who underwent continuous-flow LVAD implantation and subsequent right heart catheterization (RHC) to determine partial or complete LV unloading using invasive hemodynamics. Complete LV unloading was defined as cardiac index (CI) > 2.2 and pulmonary capillary wedge pressure (PCWP) Results Our sample size included 142 patients. Mean age 57.4 (range 25-79), 75.5% of male gender and 55% had an ischemic etiology of HF. Complete LV unloading was seen in 52 (36.6%) patients compared to 90 (63.4%) patients with partial LV unloading. There was a trend towards worse outcomes (mortality and HF readmission) in the group with partial LV unloading, however, did not reach statistical significance (Table 1). Conclusion Our institution uses invasive hemodynamics based on RHC for LVAD speed optimization and alterations in LVAD speed done at the time of RHC may potentially have played a role in influencing outcomes of the partially unloaded LV group and hence not met statistical significance. Best long-term strategy for LV unloading remains unclear at this time and further studies are needed to guide management to maintain favorable long-term outcomes.

Echocardiographic and Hemodynamic Parameters Associated with Diminishing Renal Filtration among Patients with Heart Failure with Preserved Ejection Fraction

Background: Renal dysfunction is an important predictor of poor outcomes in patients with heart failure with preserved ejection fraction (HFpEF). Right ventricular (RV) dysfunction is implicated as one of the explanations for worsening renal function in cardiorenal syndrome. Novel right heart catheterization (RHC) parameters such as pulmonary artery pulsatility index (PAPi) and right atrial to pulmonary capillary wedge pressure ratio (RA:PCWP) have been found as predictors of RV dysfunction. However, most studies investigating these parameters have been done in the setting of myocardial infarction or left ventricular assist device implantation, with limited data on these metrics in patients with HFpEF. Objective: The purpose of this study was to determine whether novel RHC parameters such as RA:PCWP and PAPi correlate with long-term renal outcomes among patients with HFpEF. Methods: A retrospective single-center study of adult patients with a documented diagnosis of heart failure who had RHC was performed between January 2006 and December 2010 at Einstein Med ical Center Philadelphia. Selected patients also had a serum B-type natriuretic peptide level ≥100 pg/mL and a PCWP ≥15 mm Hg. Patients with an ejection fraction < 50%, including those with recovered ejection fraction, and end-stage renal disease were excluded. Results: A total of 81 patients with a clinical diagnosis of HFpEF were identified who met the inclusion criteria. On multivariate analysis, after adjusting for age, sex, race, diabetes, hypertension, and cardiac index, PAPi was associated with long-term estimated glomerular filtration rate (eGFR) (β = 3.43, 95% CI = 0.635–6.23, p = 0.017), and RA:PCWP showed a trend towards significance (β = 14.81, 95% CI = –0.096–29.73, p = 0.051). The results were unchanged after further adjustment for eGFR at the time of RHC. Conclusion: Novel hemodynamic indices obtained by RHC may have predictive value for long-term renal dysfunction in patients with HFpEF.