Higher Pulmonary Capillary Wedge Pressure Research Articles

Diagnosis of heart failure with preserved ejection fraction

Heart failure with preserved ejection fraction (HFpEF) currently causes about half of the heart failure related hospitalizations. With the aging of the population and increasing prevalence of risk factors and comorbidities, such as arterial hypertension, diabetes mellitus and obesity, HFpEF prevalence is expected to increase as well. With regards to quality of life, overall morbidity, and mortality, HFpEF patients have a similarly adverse prognosis as patients with heart failure with reduced ejection fraction. The leading symptoms of exertional dyspnea and exercise intolerance with concomitant clinical signs of heart failure should, therefore, prompt diagnostic tests to exclude or confirm HFpEF. Considering the main pathophysiological mechanisms, echocardiography is crucial to non-invasively identify signs of left ventricular (LV) hypertrophy, impaired myocardial relaxation, and elevated filling pressures. Elevated NT-proBNP may furthermore indicate increased LV wall stress and volume overload. If the results of these investigations are inconclusive, parameters of elevated filling pressures can be measured invasively by right or left heart catheterization. High pulmonary capillary wedge pressure (PCWP) or left ventricular end-diastolic pressure (LVEDP) may confirm a HFpEF diagnosis. Ongoing studies are investigating potential distinct phenotypes within the HFpEF patient group.

Is Pulmonary Capillary Wedge Pressure a Reliable Indicator of Postcapillary Pulmonary Hypertension?

Although current pulmonary hypertension (PH) guidelines recommend a pulmonary capillary wedge pressure (PCWP) above 15 mmHg for the detection of a post-capillary component, the rational of this recommendation may not be quite compatible with the peculiar hemodynamics of PH. We hypothesize that a high PCWP alone does not necessarily indicate left-sided disease and this diagnosis can be improved using LV transmural pressure difference (∆PTM). In this two-center, retrospective, observational study; we enrolled 1070 patients with PH who had undergone heart catheterization with the final study population comprising of 961 cases. ∆PTM was calculated as PCWP minus right atrial pressure. The patients with group II PH had significantly higher ∆PTM values (12.6 ± 6.6 mmHg) compared to the other groups (1.1 ± 4.8 in group I, 12.4 ± 6.6 in group II, 2.5 ± 6.4 in group III and 0.8 ± 8.0 in group IV, P<0.001) despite overlapping PCWP values. A ∆PTM cut-off of 7 mmHg identifies left-heart disease when PCWP>15 (area under curve, 0.825; 95% confidence interval, 0.784 to. 0.866; P<0.001). Five-year mortality was significantly higher in patients with high ∆PTM and PCWP subgroup compared to low ∆PTM plus high PCWP (26.1% vs. 18.5%, P=0.027), and low ∆PTM and PCWP subgroups (26.1% vs. 15.6%, P<0.001). ∆PTM has supplementary discriminatory power in distinguishing patients with and without post-capillary PH. In conclusion, a new approach utilizing ∆PTM may improve our understanding of PH pathophysiology and may identify a subpopulation who may potentially benefit from PH-specific treatments.

Correlation between non-invasive measurements and intracardiac pressures using machine learning techniques

Abstract Background Solutions targeting early recognition of congestion in heart failure (HF) patients have the potential to prevent readmissions and can thus significantly reduce the burden on HF care. A gold standard measure of congestion is the invasively measured pulmonary capillary wedge pressure (PCWP). However, the invasive nature and accessibility of this measurement limits its clinical use. Non-invasive approximation of the PCWP using biosensing wearables could be a promising replacement for HF monitoring. Purpose The primary aim of this retrospective study was to create a model that estimates the PCWP based on non-invasive measurements of vital signs using both traditional statistics and machine learning (ML) techniques. Methods The study cohort consisted of right-sided heart catheterizations between 23/6/2017 and 19/8/2022. The following models were used: linear regression or classification, k-nearest neighbors, random forest, gradient boosting and multilayer perceptron. The outcome measure for the regression models was the continuous PCWP as measured during the catheterization. The two outcome classes for the classification models were low (&amp;lt;12 mmHg) and high (≥12 mmHg) PCWP. Non-invasive mean arterial blood pressure (MAP), saturation, heart rate, weight and temperature measured at most 72 hours before or after the catheterization were collected as the features for the models. Additionally, ECG-signals acquired during the catheterization were used to calculate the heart rate variability (HRV). The data was split in a validation (20%) and training (80%) data set. The models were built based on the training set and then applied on the validation set to determine the coefficient of determination (R2) for the regression models and the AUC of the ROC for the classification models. Results A total of 859 catheterizations were included of which 31.2% had HF as primary diagnosis. Average age of the cohort was 59 ± 14 years and 52.2% were male. In the HF group, the features with the highest correlation with the PCWP were the HRV and gender (Table 1). All the used regression techniques resulted in low R2 values of up to 0.10 and the classification techniques in AUC of the ROC values of up to 0.61 (Table 2). Conclusion In the current study, PCWP could not be approximated with non-invasive measurements using traditional statistics and ML techniques. These findings support the notion that traditional measures for monitoring HF are poorly correlated with hemodynamic parameters. Perhaps repeated measurements over time could overcome the shortcomings of a single vital signs measurement for congestion evaluation. Future prospective research is needed to evaluate the potential of wearable devices measuring trends over a longer period and their potential in predicting hemodynamics.

Right heart catheterization predictors of symptomatic improvement in patients undergoing transcatheter tricuspid valve edge‐to‐edge repair

AbstractBackgroundTranscatheter tricuspid valve edge‐to‐edge repair (TTEER) is associated with improvement in outcomes for symptomatic patients with severe tricuspid regurgitation (TR). However, reliable predictors for clinical success are not yet fully defined. This study aims to describe right heart catheterization (RHC) findings in patients referred for TTEER and identify hemodynamic characteristics of patients who experience immediate symptomatic improvement following successful TR intervention.MethodsPatients who underwent TTEER and had a separate RHC within the preceding 6 months were included. Hemodynamic tracings from the RHC and TTEER procedures were reviewed and recorded. Clinical success was defined as a successful device implant with at least 1‐grade of TR reduction and improvement in NYHA class by 1 or more grades on 30‐day echocardiogram and clinical follow‐up.ResultsThirteen patients underwent an RHC within 6 months of TTEER procedure (median age 76 years [IQR: 73–80]). All patients were on a stable dose of loop diuretics. Baseline right atrial pressure was severely elevated (mean 19 mmHg [IQR: 9–24 mmHg]) with prominent CV waves. Median pulmonary capillary wedge pressure (PCWP) was 20 mmHg (IQR: 14–22) and 70% of patients had a mean PCWP &gt; 15 mmHg at rest. Median PCWP CV‐wave was 34 mmHg (IQR: 23–42). Higher PCWP CV‐wave height (40 mmHg [IQR 33–43] versus 18 mmHg [IQR 17–31]) was associated with lower likelihood of clinical success (OR 0.83, 95% CI: 0.35–0.97,p = 0.04).ConclusionsInclusion of invasive hemodynamics as part of pre‐TTEER evaluation may allow for improved TR phenotyping and patient selection. Patients with a large left atrial CV wave on resting RHC were less likely to experience immediate symptomatic improvement despite procedural success with TTEER.

SERCA2a Agonist Effects on Cardiac Performance During Exercise in Heart Failure With Preserved Ejection Fraction

BackgroundImpaired ventricular relaxation influences left ventricular pressures during exercise in heart failure with preserved ejection fraction (HFpEF). Sarco/endoplasmic reticulum calcium-adenosine triphosphatase (SERCA2a) facilitates myocardial relaxation by increasing calcium reuptake and is impaired in HFpEF. ObjectivesThis study sought to investigate the effects of istaroxime, a SERCA2 agonist, on lusitropic and hemodynamic function during exercise in patients with HFpEF and control subjects. MethodsEleven control subjects (7 male, 4 female) and 15 patients with HFpEF (8 male, 7 female) performed upright cycle exercise with right-sided heart catheterization. Participants received istaroxime (0.5 μg/kg/min) or saline placebo (single-blind, crossover design). Cardiac output, pulmonary capillary wedge pressure (PCWP), and diastolic function were measured at rest and during submaximal exercise. In an exploratory analysis (Hedge's g), 7 patients with HFpEF received higher-dose istaroxime (1.0 μg/kg/min). End-systolic elastance (Ees) was calculated by dividing systolic blood pressure (SBP) × 0.9 by end-systolic volume (ESV) (on 3-dimensional echocardiography). ResultsPatients with HFpEF had higher PCWP (25 ± 10 mm Hg vs 12 ± 5 mm Hg; P < 0.001) and lower tissue Doppler velocities during exercise. Istaroxime (0.5 μg/kg/min) had no effect on resting or exercise measures in patients with HFpEF or control subjects. Control subjects had a larger increase in Ees (Δ 1.55 ± 0.99 mm Hg/mL vs Δ 0.86 ± 1.31 mm Hg/mL; P = 0.03), driven by lower ESV. Comparing placebo and istaroxime 1.0 μg/kg/min during exercise, PCWP during the 1.0 μg/kg/min istaroxime dose was slightly lower (Δ 2.2 mm Hg; Hedge's g = 0.30). There were no effects on diastolic function, but there were increases in SBP and s′, suggesting a mild inotropic effect. ConclusionsLow-dose istaroxime had no effect on cardiac filling pressure or parameters of relaxation in patients with HFpEF during exercise. Higher doses of istaroxime may have been more effective in reducing exercise PCWP in patients with HFpEF. (Hemodynamic Response to Exercise in HFpEF Patients After Upregulation of SERCA2a; NCT02772068)

Reducing Pulmonary Capillary Wedge Pressure During Exercise Exacerbates Exertional Dyspnea in Patients With Heart Failure With Preserved Ejection Fraction: Implications for [formula omitted] Mismatch

The primary cause of dyspnea on exertion in heart failure with preserved ejection fraction (HFpEF) is presumed to be the marked rise in pulmonary capillary wedge pressure during exercise; however, this hypothesis has never been tested directly. Therefore, we evaluated invasive exercise hemodynamics and dyspnea on exertion in patients with HFpEF before and after acute nitroglycerin (NTG) treatment to lower pulmonary capillary wedge pressure. Does reducing pulmonary capillary wedge pressure during exercise with NTG improve dyspnea on exertion in HFpEF? Thirty patients with HFpEF performed two invasive 6-min constant-load cycling tests (20 W): one with placebo (PLC) and one with NTG. Ratings of perceived breathlessness (0-10 scale), pulmonary capillary wedge pressure (right side of heart catheter), and arterial blood gases (radial artery catheter) were measured. Measurements of V˙/Q˙ matching, including alveolar dead space (Vdalv; Enghoff modification of the Bohr equation) and the alveolar-arterial Po2 difference (A-aDO2; alveolar gas equation), were also derived. The ventilation (V˙e)/CO2 elimination (V˙co2) slope was also calculated as the slope of the V˙e and V˙co2 relationship, which reflects ventilatory efficiency. Ratings of perceived breathlessness increased (PLC: 3.43 ± 1.94 vsNTG: 4.03 ± 2.18; P= .009) despite a clear decrease in pulmonary capillary wedge pressure at 20W (PLC: 19.7 ± 8.2 vsNTG: 15.9 ± 7.4mmHg; P< .001). Moreover, Vdalv (PLC: 0.28 ± 0.07 vsNTG: 0.31 ± 0.08 L/breath; P= .01), A-aDO2 (PLC: 19.6 ± 6.7 vsNTG: 21.1 ± 6.7; P= .04), and V˙e/V˙co2 slope (PLC: 37.6 ± 5.7 vsNTG: 40.2 ± 6.5; P< .001) all increased at 20W after a decrease in pulmonary capillary wedge pressure. These findings have important clinical implications and indicate that lowering pulmonary capillary wedge pressure does not decrease dyspnea on exertion in patients with HFpEF; rather, lowering pulmonary capillary wedge pressure exacerbates dyspnea on exertion, increases V˙/Q˙ mismatch, and worsens ventilatory efficiency during exercise in these patients. This study provides compelling evidence that high pulmonary capillary wedge pressure is likely a secondary phenomenon rather than a primary cause of dyspnea on exertion in patients with HFpEF, and a new therapeutic paradigm is needed to improve symptoms of dyspnea on exertion in these patients.

Diabetes mellitus and hemodynamics in advanced heart failure

BackgroundThe presence of diabetes in patients with heart failure (HF) is associated with a worse prognosis. It is unclear if hemodynamics in HF patients with DM differ from those of non-diabetic patients and how this might influence outcome. This study aims to discover the impact of DM on hemodynamics in HF patients. MethodsConsecutive patients (n = 598) with HF and reduced ejection fraction (LVEF ≤40%) undergoing invasive hemodynamic evaluation were included (non-DM: n = 473, DM: n = 125). Hemodynamic parameters included pulmonary capillary wedge pressure (PCWP), central venous pressure (CVP), cardiac index (CI) and mean arterial pressure (MAP). Mean follow-up was 9.5 ± 5.1 years. ResultsPatients with DM (82.7% male, mean age 57.1 ± 10.1 years, mean HbA1c 60 ± 21 mmol/mol) had higher PCWP, mPAP, CVP and higher MAP. Adjusted analysis demonstrated that DM patients had higher PCWP and CVP. Increasing HbA1c-values were correlated with higher PCWP (p = 0.017) and CVP (p = 0.043). ConclusionPatients with DM, especially those with poor glycemic control, have higher filling pressures. This may be a feature of diabetic cardiomyopathy, however, other unknown mechanisms beyond hemodynamic factors are likely to explain the increased mortality associated with diabetes in HF.

Hemodynamic Profiling and Prognosis in Cardiac Amyloidosis.

Little information is available on the prognostic relevance of cardiac hemodynamic cutoffs in cardiac amyloidosis (CA) and its subtypes. Consecutive patients diagnose with light chain-CA or transthyretin CA undergoing right heart catheterization were analyzed. Prognostic relevance of classic hemodynamic cutoffs of cardiac index (CI <2.2 L/min per m2), pulmonary capillary wedge pressure (>18 mm Hg), right atrial pressure (>8 mm Hg), and mean pulmonary artery pressure (≥25 mm Hg or pulmonary hypertension) with the combined end point of cardiac transplant/left ventricular assist device and death and heart failure admissions separately was assessed. A total of 469 CA patients underwent right heart catheterization (light chain CA=42% and transthyretin CA=52%) of whom 69%, 64%, and 79% had elevated right atrial pressure, pulmonary capillary wedge pressure, and pulmonary hypertension, respectively. The classic hemodynamic cutoffs for right atrial pressure (hazard ratio, 1.26 [0.98-1.62]) and mean pulmonary artery pressure (hazard ratio, 1.28 [0.96-1.71]) did not identify patients at higher risk for adverse outcome; however, cutoffs of 14 mm Hg for right atrial pressure (hazard ratio, 1.59 [1.26-2.00]) and 35 mm Hg for mean pulmonary artery pressure (hazard ratio, 1.30 [1.01-1.66]) performed better to detect worse outcome (P<0.05 for both). Reduced CI occurred in 55% of patients and was the strongest variable associated with the risk for cardiac transplant/left ventricular assist device and death, heart failure admissions, and reduced functional capacity. Reduced CI independently predicted risk on top of the Mayo-score in light chain CA and National Amyloid Center score in transthyretin CA (P<0.05 for both). Patients with light chain CA had higher pulmonary capillary wedge pressure and lower stroke volume index but maintained CI through a higher heart rate. Hemodynamic variables are grossly abnormal in CA, but elevated filling pressures are prognostic at significantly higher threshold values than classic cutoff values. CI is the hemodynamic variable most strongly associated with outcome and functionality in CA.

Challenging the Hemodynamic Hypothesis in Heart Failure With Preserved Ejection Fraction: Is Exercise Capacity Limited by Elevated Pulmonary Capillary Wedge Pressure?

Exercise intolerance is a defining characteristic of heart failure with preserved ejection fraction (HFpEF). A marked rise in pulmonary capillary wedge pressure (PCWP) during exertion is pathognomonic for HFpEF and is thought to be a key cause of exercise intolerance. If true, acutely lowering PCWP should improve exercise capacity. To test this hypothesis, we evaluated peak exercise capacity with and without nitroglycerin to acutely lower PCWP during exercise in patients with HFpEF. Thirty patients with HFpEF (70±6 years of age; 63% female) underwent 2 bouts of upright, seated cycle exercise dosed with sublingual nitroglycerin or placebo control every 15 minutes in a single-blind, randomized, crossover design. PCWP (right heart catheterization), oxygen uptake (breath × breath gas exchange), and cardiac output (direct Fick) were assessed at rest, 20 Watts (W), and peak exercise during both placebo and nitroglycerin conditions. PCWP increased from 8±4 to 35±9 mm Hg from rest to peak exercise with placebo. With nitroglycerin, there was a graded decrease in PCWP compared with placebo at rest (-1±2 mm Hg), 20W (-5±5 mm Hg), and peak exercise (-7±6 mm Hg; drug × exercise stage P=0.004). Nitroglycerin did not affect oxygen uptake at rest, 20W, or peak (placebo, 1.34±0.48 versus nitroglycerin, 1.32±0.46 L/min; drug × exercise P=0.984). Compared with placebo, nitroglycerin lowered stroke volume at rest (-8±13 mL) and 20W (-7±11 mL), but not peak exercise (0±10 mL). Sublingual nitroglycerin lowered PCWP during submaximal and maximal exercise. Despite reduction in PCWP, peak oxygen uptake was not changed. These results suggest that acute reductions in PCWP are insufficient to improve exercise capacity, and further argue that high PCWP during exercise is not by itself a limiting factor for exercise performance in patients with HFpEF. URL: https://www. gov; Unique identifier: NCT04068844.

Abstract 13827: Performance Characteristics of Natriuretic Peptides in Predicting Invasively Measured Intracardiac Filling Pressures in Patients With Cancer

Introduction: Natriuretic peptides (NP) are routinely used for the diagnosis of heart failure. Studies have suggested higher levels of NP in patients with cancer, possibly driven by cancer associated inflammation. This study aims to assess the performance characteristics of natriuretic peptides in predicting invasively measured elevated intracardiac filling pressures in patients with cancer. Methods: Patients with cancer who underwent a right heart catheterization (RHC) at a tertiary cancer center from 10/2011 to 10/2021 were identified. Demographic characteristics, NP levels and invasive hemodynamic data were abstracted. Pulmonary capillary wedge pressure (PCWP) &gt; 15 mmHg and mean right atrial pressure (mRAP) &gt; 8 mmHg were defined as abnormal. Results: Of 1240 patients who underwent a RHC, 740 had NTproBNP (41%) or BNP levels (23%) available within a median of 1 day (0-3, and 0-4 days, respectively) from the procedure. Of those, 46% were female, 70% were white, median age was 67 years (IQR: 58-74) and median BMI was 25.2 kg/m 2 (17.4-30.3). High PCWP was present in 58% of patients while an additional 15% had high mRAP with normal PCWP (73%). The area under the curve (AUC) of NTproBNP and BNP in predicting high PCWP was 0.626 (95% CI 0.578-0.675) and 0.681 (0.617-0.744), respectively. The AUC of NTproBNP and BNP in predicting high PCWP or high mRAP was 0.603 (0.549-0.657) and 0.690 (0.621-0.759), respectively. At 125 pg/ml, NTproBNP had a sensitivity of 95%, specificity 6%, positive predictive value (PPV) 57%, and negative predictive value (NPV) 48% for high PCWP and a sensitivity of 95%, specificity 9%, PPV of 74%, and NPV 41% for high PCWP or high mRAP. At 100 pg/ml, BNP had a sensitivity of 89%, specificity 25%, PPV 64%, and NPV 60% for high PCWP, and a sensitivity of 88%, specificity 28%, PPV 77%, and NPV 47% for high PCWP or high mRAP. Conclusions: NP at the standard cutoff levels are very sensitive in predicting elevated intracardiac filling pressures in patients with cancer. However, they can be falsely elevated in &gt;70% of cancer patients with normal filling pressures. These caveats need to be considered when utilizing elevated levels of NP in the assessment of patients with cancer and dyspnea and/or edema.

Effect of positive end-expiratory pressure on central venous pressure in the closed and open thorax

Objective. The magnitude and mechanism of the rise of central venous pressure (CVP) after positive end-expiratory pressure (PEEP) among patients with cardiac disease is poorly understood. Therefore, the study aimed to compare the magnitude of change in CVP after PEEP in patients with TR (tricuspid regurgitation), high CVP, and high PCWP (pulmonary capillary wedge pressure) and in those with no TR, low CVP, and low PCWP. Additionally, we hypothesized that PEEP in the open thorax would also lead to a rise in CVP. Approach. This prospective, quasi-experimental study was conducted in patients undergoing cardiac surgery. Three consecutive readings of variables were obtained at 1 min intervals after PEEP (5 and 10 cm H2O) application in the closed and open thorax. Patients were stratified a priori into low CVP (<10 cm H2O) and high CVP (≥10 cm H2O), no TR and TR, and low PCWP (<15 mm Hg) and high PCWP (≥15 mm Hg) in the closed and open thorax. Main Results. Sixty-two patients were eligible for final analysis. The mean difference (MD) in ΔCVP (CVP10 cm H2O of PEEP—CVP zero end-expiratory pressure) was 2.33 ± 1.13 (95% CI, 2.04–2.62, P = 0.000) and 1.02 ± 0.77 (95% CI, 0.82–1.22, P = 0.000) in the closed and open thorax, respectively. The increase in CVP was higher among patients who had a lower CVP (2.64 ± 0.9 mm Hg versus 1.45 ± 1.17 mm Hg; p=0.000), in patients without TR (2.64 ± 0.97 mm Hg versus 2.14 ± 1.2 mm Hg, p=0.09) and in patients with a lower PCWP (2.4 ± 0.9 mm Hg versus 2.3 ± 1.4 mm Hg, p=0.67) at 10 cm H2O PEEP in the closed thorax. Significance. The rise in CVP was higher among patients without TR, low CVP, and low PCWP. Zero intrathoracic pressure in the open thorax did not abolish the effect of PEEP on CVP rise altogether.

PH Grand Rounds: COVID-19 Infection Causing Delayed Pulmonary Arterial Hypertension

PH Grand Rounds: COVID-19 Infection Causing Delayed Pulmonary Arterial Hypertension

Hemodynamic Response to Acute Volume Load and Endomyocardial NO-synthase Gene Expression in Heart Transplant Recipients.

Background.A pulmonary capillary wedge pressure (PCWP) >18 mm Hg following volume load has been proposed as a partition value for the detection of heart failure with preserved ejection fraction. As hemodynamic changes in filling pressures (FP) have been attributed to a nitric oxide (NO)-mediated rightward shift of the pressure-volume relationship, we investigated the hemodynamic response to volume load in heart transplant recipients (HTx) and examined the role of inducible NO synthase (iNOS) gene expression on diastolic function changes.Methods.In 36 HTx, FPs were measured before and after volume load, following which Starling curves were constructed using PCWP and cardiac index (CI). Patients were categorized into those with normal (group A, n = 21) and abnormal hemodynamics (group B, n = 15, PCWP >15 mm Hg at rest or >18 mm Hg following volume load). For the establishment of the potential role of NO, endomyocardial iNOS gene expression level was measured.Results.Except for PCWP (P < 0.001) and mean pulmonary artery pressure (P < 0.001) no differences in age, baseline characteristics, and ejection fraction were observed between both groups, and volume load significantly increased PCWP in both groups (group A: P < 0.001 and group B: P < 0.001) without any change in heart rate. Interestingly, volume load significantly increased CI in group A (P < 0.001) but not in group B (P = 0.654), and the Starling curves revealed a higher CI at any given PCWP in group A together with significantly higher iNOS gene expression (P = 0.009).Conclusions.In HTx, volume load increases FP and unmasks the presence of left ventricular diastolic dysfunction. Interestingly, following saline load group B shows a blunted Starling response, with higher PCWP and lack of CI increase at any given PCWP. The higher iNOS gene expression level in group A suggests a potential role of NO as mediator of diastolic function.

Differences in the expression of DNA methyltransferases and demethylases in leukocytes and the severity of pulmonary arterial hypertension between ethnic groups.

The loss of ten‐eleven translocation (TET2) methylcytosine dioxygenase expression contributes to the pathobiology of pulmonary arterial hypertension (PAH). However, whether the expression and activity of other TETs and DNA methyltransferases (DNMTs) are altered in PAH remains enigmatic. Therefore, our objective was to determine the expression of DNMT (1, 3a, and 3b) and TET (1, 2, and 3) and their total activity. We assessed the expression of DNMT and TET enzymes in the leukocytes and their activity in extracellular vesicles (EVs). Expression of DNMT (1, 3a, and 3b), TET (2 and 3) in leukocytes, and total activity in EVs, from PAH patients was higher than in healthy controls. Additionally, we noticed there were difference in expression of these epigenetic enzyme based on ethnicity and found higher DNMT1 and lower TET2/TET3 expression in Caucasian than Hispanic/African American (combine) patients. Since loss‐of‐function mutation(s) and down‐regulation of TET enzymes are associated with hematological malignancies and cytokine production, we determined the expression of genes that encode cytokines in samples of Caucasian and Hispanic/African American patients. Expression of IL6, CSF2, and CCL5 genes were higher in the leukocytes of Caucasian than Hispanic/African American patients, and CSF2 and CCL5 negatively correlated with the decreased expression of TET3. Interestingly, the expression of gene encoding CD34, a marker of myeloid and lymphoid precursor cells, and CD163, a monocyte/macrophage protein, was higher in the leukocytes of Caucasian than Hispanic/African American patients. Furthermore, Hispanic/African American patients having higher TET2/TET3 expression had higher pulmonary capillary wedge pressure. In conclusion, our results revealed higher DNMT1 and lower TET2/TET3 in Caucasian than Hispanic/African American patients together potentially augmented genes encoding inflammation causing cytokines, and CD34+‐derived immunogenic cells, and the severity of PAH.

Prognostication Of Pulmonary Artery Pulsatility Index And Pulmonary Capillary Wedge Pressure In Patients Requiring Impella Support

<h3>Introduction</h3> Pulmonary Artery Pulsatility Index (PaPi) was initially described to identify patients at risk for right ventricular dysfunction after inferior wall myocardial infarctions. The formula has since been applied to patients with advanced heart failure and pulmonary arterial hypertension to predict adverse outcomes. However, there is a lack of data regarding the utility of PaPi in assessing outcomes in patients requiring Impella 2.5 and CP - temporary left ventricular support devices. <h3>Hypothesis</h3> Lower PaPi and higher PCWP will be associated with increased mortality after Impella placement. <h3>Methods</h3> All patients admitted to York Hospital requiring Impella support due to cardiogenic shock between January 1, 2018 and May 1, 2020 were included in this retrospective study. Baseline characteristics and in-hospital mortality months were compared for hemodynamic variables including pulmonary capillary wedge pressure (PCWP) and PaPi. These numbers were collected and analyzed after Impella placement, 24 hours later, and the day of removal using ANOVA, logistic regression, and Fisher's exact test. <h3>Results</h3> There were 32 patients who met inclusion criteria. At time of Impella implantation, the cohort had an average age of 67.6 + 9.9, ejection fraction of 24.62 + 13.09%, brain natriuretic peptide of 772.03 + 1103.8 pg/dL, and lactate of 4.634 + 4.194 mmol/L. The average duration of Impella support was 2.6875 + 1.89 days. Pulmonary artery pulsatility index was strongly associated with in-hospital mortality at values less than 1.2 after Impella placement (p = 0.0325) and on the day of removal (p = 0.0003). Increasing PCWP strongly correlated with in-hospital mortality after Impella placement (p = 0.0179) and on the day of removal (p = 0.0032). Neither PCWP nor PaPi correlated with mortality at 24 hours. <h3>Conclusions</h3> In patients requiring Impella support for cardiogenic shock, PaPi and PCWP are significant predictors of in-hospital mortality. These variables are strongly associated with mortality after Impella placement and on the day of removal. PaPi is a better predictor of poor outcomes at lower values, as values less than 1.2 strongly correlated with mortality. Increasing PCWP will invariably increase the value of PaPi due to the effects of PCWP on pulmonary artery capacitance. Patients with worsening left ventricular dysfunction will thus have higher values of PaPi. A lower PaPi may be an ominous sign in patients requiring mechanical support, but further studies should be done to further assess its prognostic role.

Dimethyl malonate slows succinate accumulation and preserves cardiac function in a swine model of hemorrhagic shock.

Succinate (SI) is a citric acid cycle metabolite that accumulates in tissues during hemorrhagic shock (HS) due to electron transport chain uncoupling. Dimethyl malonate (DMM) is a competitive inhibitor of SI dehydrogenase, which has been shown to reduce SI accumulation and protect against reperfusion injury. Whether DMM can be therapeutic after severe HS is unknown. We hypothesized that DMM would prevent SI buildup during resuscitation (RES) in a swine model of HS, leading to better physiological recovery after RES. The carotid arteries of Yorkshire pigs were cannulated with a 5-Fr catheter. After placement of a Swan-Ganz catheter and femoral arterial line, the carotid catheters were opened and the animals were exsanguinated to a mean arterial pressure (MAP) of 45 mm. After 30 minutes in the shock state, the animals were resuscitated to a MAP of 60 mm using lactated ringers. A MAP above 60 mm was maintained throughout RES. One group received 10 mg/kg of DMM (n = 6), while the control received sham injections (n = 6). The primary end-point was SI levels. Secondary end-points included cardiac function and lactate. Succinate levels increased from baseline to the 20-minute RES point in control, while the DMM cohort remained unchanged. The DMM group required less intravenous fluid to maintain a MAP above 60 (450.0 vs. 229.0 mL; p = 0.01). The DMM group had higher pulmonary capillary wedge pressure at the 20-minute and 40-minute RES points. The DMM group had better recovery of cardiac output and index during RES, while the control had no improvement. While lactate levels were similar, DMM may lead to increased ionized calcium levels. Dimethyl malonate slows SI accumulation during HS and helps preserve cardiac filling pressures and function during RES. In addition, DMM may protect against depletion of ionized calcium. Dimethyl malonate may have therapeutic potential during HS.

A Novel Three-Dimensional and Tissue Doppler Echocardiographic Index for Diagnosing and Prognosticating Heart Failure With Preserved Ejection Fraction.

IntroductionThe diagnosis of heart failure with preserved ejection fraction (HFpEF) remains challenging. In this study, a novel echocardiography index based on three-dimensional and tissue Doppler echocardiography for diagnosing and estimating prognosis in HFpEF.Materials and MethodsPatients with symptoms and/or signs of heart failure and normal left ventricular ejection fraction (LVEF ≥50%) who underwent right heart catheterization were screened. Patients were divided based on pulmonary capillary wedge pressure (PCWP) of ≥15 mmHg and PCWP <15 mmHg. A diagnosis of HFpEF was confirmed by PCWP of ≥15 mmHg according to ESC guidelines. A novel index was calculated by the ratio between stroke volume standardized to body surface area (SVI) and tissue Doppler mitral annulus systolic peak velocity S' (SVI/S'). Its diagnostic and prognostic values were determined.ResultsA total of 104 patients (mean age 64 ± 12 years) were included. Of these, 63 had PCWP ≥15 mmHg and 41 patients had PCWP <15 mmHg. Compared to the PCWP <15 mmHg group, the ≥15 mmHg group had a significantly lower SVI/S' (P < 0.001). Logistic regression showed that SVI/S' was associated with high PCWP measured invasively. The SVI/S' had an area under the curve of 0.761 for diagnosing classifying between PCWP ≥15 mmHg and <15 mmHg. Kaplan–Meier analysis showed that the lower SVI/S' group showed a poorer prognosis.ConclusionsSVI/S' is a non-invasive index calculated by three-dimensional and tissue Doppler echocardiography. It is a surrogate measure of PCWP and can be used to diagnose and determine prognosis in HFpEF.

Abstract 11760: Reducing Pulmonary Capillary Wedge Pressure During Exercise Does Not Improve Exercise Capacity in Heart Failure With Preserved Ejection Fraction

Background: Exercise intolerance is a defining characteristic of heart failure with preserved ejection fraction (HFpEF). A marked rise in pulmonary capillary wedge pressure (PCWP) during exertion is pathognomonic for HFpEF and is thought to be a key cause of exercise intolerance. If true, acutely lowering PCWP would improve exercise capacity. To test this hypothesis, we evaluated peak exercise capacity with and without nitroglycerin (NTG) to acutely lower PCWP during exercise in patients with HFpEF. Methods: In a preliminary analysis of a clinical trial, 15 patients with HFpEF (69±6 years, 60% female) underwent 2 upright, seated cycle exercise tests dosed with sublingual NTG or placebo control (CON), every 15 minutes in a single-blind, cross-over design. A right heart catheter was used to measure end-expiratory PCWP and cardiac output (Qc, direct Fick). Oxygen uptake was measured using breath-by-breath system. Measures were made at rest, 20W, and peak exercise. Results: PCWP increased from 6.0±2.4 to 33.7±7.4 mmHg from rest to peak exercise with placebo. With NTG, PCWP increased significantly less from 4.5±3.1 to 26.3±5.9 mmHg (drug x exercise p = 0.019). There was no change in peak VO 2 with NTG (CON: 1.25±0.36 vs NTG: 1.26±0.41 L/min, drug x exercise p = 0.986, Figure ). Peak Qc was similar between conditions (Qc: CON 10.4±2.3 vs 10.8±3.2 L/min). During submaximal exercise, PCWP was lower with NTG with no difference in VO 2 (PCWP: CON 21.2±6.5 vs NTG 16.6±6.4 mm Hg, VO 2 CON:0.87±0.17 vs NTG 0.86±0.17 L/min) but with a lower stroke volume (NTG: 90±18 vs CON: 98±21 ml). Conclusions: Sublingual nitroglycerin effectively lowered PCWP during submaximal and maximal exercise. Despite this reduction in PCWP, peak VO 2 was not changed. These results suggest acutely lowering PCWP is insufficient to improve exercise capacity and raises the possibility that high PCWP during exercise is a secondary phenomenon rather than a primary cause of exercise intolerance in patients with HFpEF.

Abstract 9925: Impaired Cardiac Output and Peripheral Reserve Predict Morbidity and Mortality in Heart Failure and Preserved Ejection Fraction

Introduction: Reduced peak oxygen consumption (VO 2 ) is common and associated with adverse outcomes in patients with heart failure (HF) and preserved ejection fraction (HFpEF). According to the Fick principle, VO 2 is equal to the product of cardiac output (CO) and arterial-venous O 2 difference (AVO 2 diff). Patients with HFpEF display abnormalities each component, but no study has yet evaluated their prognostic impacts. Methods: Patients with HFpEF (n=501) and controls without HF (n=207) underwent invasive hemodynamic exercise testing with expired gas analysis and clinical follow up for the composite event of HF hospitalization or death. Results: Compared to controls, patients with HFpEF displayed slightly lower CO at rest with higher pulmonary capillary wedge pressure (PCWP). On exercise, subjects with HFpEF displayed blunted increases in CO and greater increase in PCWP (Figure A). As compared with controls, the slope of the increase in CO relative to VO 2 was lower in HFpEF (6.4 ± 3.3 vs 5.4 ± 3.2 L/L; P =0.0004), while augmentation in AVO 2 diff relative to VO 2 was greater in HFpEF (7.7 ± 5.4 vs 10.0 ± 5.6 min/dL; P &lt;0.0001). Over a median 2.8 (1.1-4.6) years of follow up, 101 patients experienced the composite event. Patients with CO reserve below the median and increases in AVO 2 diff below median displayed higher risk of the composite endpoint (Figure B-C). After adjustments for age, sex, BMI, atrial fibrillation, LV mass, and EF, CO reserve remained strongly associated with the primary outcome (HR [95%CI] = 0.51 [0.38-0.68]; P &lt;0.0001, per 1 SD increase) and the change of AVO 2 diff remained significant, but was less predictive (HR [95%CI] = 0.74 [0.60-0.92]; P =0.007, per 1 SD increase) in patients with HFpEF. Conclusions: Impaired ability to augment CO and peripheral O 2 delivery are associated with increasing risk of adverse events in HFpEF. Further study is required to identify therapeutic interventions targeting these hemodynamic perturbations to improve outcomes in HFpEF.

Hallazgos clínicos asociados con una descarga hemodinámica del ventrículo izquierdo incompleta en pacientes con asistencia ventricular izquierda

Introduction and objectivesThe effect of a centrifugal continuous-flow left ventricular assist device (cfLVAD) on hemodynamic left ventricular unloading (HLVU) and the clinical conditions that interfere with hemodynamic optimization are not well defined. MethodsWe retrospectively evaluated the likelihood of incomplete HLVU, defined as high pulmonary capillary wedge pressure (hPCWP)> 15mmHg in 104 ambulatory cfLVAD patients when the current standard recommendations for cfLVAD rotor speed setting were applied. We also evaluated the ability of clinical, hemodynamic and echocardiographic variables to predict hPCWP in ambulatory cfLVAD patients. ResultsTwenty-eight percent of the patients showed hPCWP. The variables associated with a higher risk of hPCWP were age, central venous pressure, absence of treatment with renin-angiotensin-aldosterone system inhibitors, and brain natriuretic peptide levels. Patients with optimal HLVU had a 15.2±14.7% decrease in postoperative indexed left ventricular end-diastolic diameter compared with 8.9±11.8% in the group with hPCWP (P=.041). Independent predictors of hPCWP included brain natriuretic peptide and age. Brain natriuretic peptide <300 pg/mL predicted freedom from hPCWP with a negative predictive value of 86% (P <.0001). ConclusionsAn optimal HLVU can be achieved in up to 72% of the ambulatory cfLVAD patients when the current standard recommendations for rotor speed setting are applied. Age, central venous pressure and therapy with renin-angiotensin-aldosteron system inhibitors had a substantial effect on achieving this goal. Brain natriuretic peptide levels and the magnitude of reverse left ventricular remodeling seem to be useful noninvasive tools to evaluate HLVU in patients with functioning cfLVAD.