Influence of socioeconomic status on rates of advanced heart failure therapies.

BACKGROUND: Socioeconomic deprivation is associated with a lower likelihood of referral for advanced heart failure (HF) evaluation, but it is not known whether it influences rates of advanced HF therapies independently of key hemodynamic measures and comorbidity following advanced HF evaluation in a universal healthcare system. METHODS: We linked data from a single-center Danish clinical registry of consecutive patients evaluated for advanced HF with patient-level information on socioeconomic status. Patients were divided into groups based on the level of education (low, medium, and high), combined degree of socioeconomic deprivation (low, medium, and high), and household income quartiles. Rates of the combined outcome of left ventricular assist device implantation or heart transplantation (advanced HF therapy) with death as a competing risk were estimated with cumulative incidence functions, and Cox proportional hazards models adjusted for age, sex, central venous pressure, cardiac index, and comorbidities. RESULTS: We included 629 patients, median age 53 years, of whom 77% were men. During a median follow-up of 5 years, 179 (28%) underwent advanced HF therapy. The highest level of education was associated with higher rates (high vs low, adjusted HR 1.81 95% CI 1.14-2.89, p = 0.01), whereas household income quartile groups (Q4 vs Q1, adjusted HR 1.37 95% CI 0.76-2.47, p = 0.30) or groups of combined socioeconomic deprivation (high vs low degree of deprivation, adjusted HR 0.86 95% CI 0.50-1.46, p = 0.56) were not significantly associated with rates of advanced HF therapy. CONCLUSIONS: Patients with a lower level of education might be disfavored for advanced HF therapies and could require specific attention in the advanced HF care center.

Importance of heart failure duration for development of pulmonary hypertension in advanced heart failure.

BACKGROUND AND OBJECTIVES: Pulmonary vascular resistance (PVR) is critical when evaluating candidacy for advanced heart failure (HF) therapies, but risk factors for elevated PVR are not well studied. We hypothesized that HF duration would be associated with elevated PVR. METHODS: Danish single-center registry of consecutive in- and outpatients undergoing right heart catheterization as part of advanced HF work up. The relation between HF duration and PVR was estimated by regression analysis. Finally, the relation between PVR and long-term mortality was assessed by Cox proportional hazards regression and Kaplan-Meier analyses. RESULTS: A total of 549 patients (77% men, median age 54 (43-61) years, median HF duration 1.6 years (0.1-7.1)) were included. Univariate linear regression displayed an association between longer HF duration and increasing PVR (p = 0.014). PVR > 3 WU was present in 92 patients (17%) who were older (median p < 0.001) and had longer HF duration (p = 0.03). HF duration (per 1 year increase) did not predict PVR > 3 WU after adjustment for covariables (OR 1.00; p = 0.99). During a mean follow-up time of 4.5 years, there were 240 (44%) deaths. Increasing PVR was associated with elevated all-cause mortality risk (adjusted HR 1.24; p < 0.001). PVR > 3 WU was associated with higher mortality (adjusted HR 1.49; p = 0.027). CONCLUSION: Longer duration of HF was associated with higher PVR in patients with advanced HF, but this association disappeared in multivariate analyses. Longer HF duration per se likely does not cause elevated PVR and should not discourage evaluation for heart transplantation.

Diabetes mellitus and hemodynamics in advanced heart failure.

BACKGROUND: The 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. METHODS: Consecutive 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. RESULTS: Patients 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). CONCLUSION: Patients 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.

Hyponatremia in Stable Patients with Advanced Heart Failure: Association to Hemodynamics and Outcome.

INTRODUCTION: Hyponatremia is associated with worse outcomes in patients with chronic heart failure (HF) and reduced ejection fraction (HFrEF). However, it is unclear whether the worse prognosis is driven by hemodynamic derangement and how this potentially could be associated with hyponatremia. METHODS: The study included 502 patients with HFrEF evaluated for advanced HF therapies, who underwent a right heart catheterization (RHC). Hyponatremia was defined as p-Na ≤136 mmol/L. The risk of all-cause mortality and a composite endpoint including mortality, left ventricular assist device (LVAD) implantation, implantation of total artificial heart (TAH), or heart transplantation (HTx) was evaluated using Cox regression analyses and Kaplan-Meier models. RESULTS: Included patients were predominantly men 79% and had a median age of 54 years (IQR: 43-62). A third (165) of the patients had hyponatremia. In both univariate and multivariate regression analyses, p-Na was associated with increased central venous pressure (CVP), pulmonary capillary wedge pressure (PCWP), and mean pulmonary artery pressure (mPAP) but not with cardiac index. Hyponatremia was significantly associated with the combined endpoint (HR: 1.36 [95% CI, 1.07-1.74]; p = 0.01), but not all-cause mortality in adjusted Cox models. CONCLUSION: In stable HFrEF patients evaluated for advanced HF therapies, lower p-Na was associated with more deranged invasive hemodynamic measurements. Hyponatremia remained significantly associated with the combined endpoint but not all-cause mortality in adjusted Cox models. The study suggests that the increased mortality associated with hyponatremia in HFrEF patients could partly be driven by hemodynamic derangement.

Uric acid in advanced heart failure: relation to central haemodynamics and outcome.

OBJECTIVE: The role of hyperuricaemia as a prognostic maker has been established in chronic heart failure (HF) but limited information on the association between plasma uric acid (UA) levels and central haemodynamic measurements is available. METHODS: A retrospective study on patients with advanced HF referred for right heart catherisation. Regression analyses were constructed to investigate the association between UA and haemodynamic variables. Cox models were created to investigate if UA was a significant predictor of adverse outcome where log1.1(UA) was used to estimate the effect on outcome associated with a 10% increase in UA levels. RESULTS: A total of 228 patients were included (77% males, age 49±12 years, mean left ventricular ejection fraction (LVEF) of 17%±8%). Median UA was 0.48 (0.39-0.61) mmol/L. UA level was associated to pulmonary capillary wedge pressure (PCWP) and cardiac index (CI) in univariable (both p<0.001) and multivariable regression analysis (p<0.004 and p=0.025 for PCWP and CI). When constructing multivariable Cox models including PCWP, CI, central venous pressure, age, estimated glomerular filtration rate (eGFR), use of loop diuretics and LVEF, log1.1(UA) independently predicted the combined endpoint (left ventricular assist device, total artificial heart implantation, heart transplantation or all-cause mortality) (hazard ratio (HR): 1.10 (1.03-1.17), p=0.004) as well as all-cause mortality (HR: 1.15 (1.06-1.25), p=0.001). CONCLUSIONS: Elevated UA is associated with greater haemodynamic impairment in advanced HF. In adjusted Cox models (age, eGFR, LVEF and haemodynamics), UA predicts the combined endpoint and all-cause mortality in long-term follow-up.

Aortic Pulsatility Index: A New Haemodynamic Measure with Prognostic Value in Advanced Heart Failure.

AIM: To test if the newly described haemodynamic variable, aortic pulsatility index (API), predicts long-term prognosis in advanced heart failure (HF). METHODS: A single-centre study on 453 HF patients (median age: 51 years; left ventricular ejection fraction [LVEF]: 19% ± 9%) referred for right heart catheterisation. API was calculated as pulse pressure/pulmonary capillary wedge pressure. RESULTS: Log(API) correlated significantly with central venous pressure (CVP; p<0.001) and cardiac index (p<0.001) in univariable regression analysis. CVP remained associated with log(API) in a multivariable analysis including cardiac index, heart rate, log(NT-proBNP [N-terminal proB-type natriuretic peptide]), LVEF, New York Heart Association (NYHA) class III or IV and sex (p=0.01). In univariable Cox models, log(API) was a significant predictor of freedom from the combined endpoint of death, left ventricular assist device implantation, total artificial heart implantation or heart transplantation (HR 0.33; (95% CI [0.22-0.49]); p<0.001) and all-cause mortality (HR 0.56 (95% CI [0.35-0.90]); p=0.015). After adjusting for age, sex, NYHA class III or IV and estimated glomerular filtration rate in multivariable Cox models, log(API) remained a significant predictor for the combined endpoint (HR 0.33; 95% CI [0.20-0.56]; p<0.001) and all-cause mortality (HR 0.49; 95% CI [0.26-0.96]; p=0.034). CONCLUSION: API was strongly associated with right-sided filling pressure and independently predicted freedom from the combined endpoint and all-cause mortality.

Plasma Somatostatin in Advanced Heart Failure: Association with Cardiac Filling Pressures and Outcome.

BACKGROUND: Somatostatin inhibits intestinal motility and hormonal secretion and is a potent arterial vasoconstrictor of the splanchnic blood flow. It is unknown if somatostatin concentrations are associated with central hemodynamic measurements in patients with advanced heart failure (HF). METHODS: A prospective study of HF patients with a left ventricular ejection fraction (LVEF) <45% referred to right heart catheterization (RHC) for evaluation for heart transplantation (HTX) or left ventricular assist device (LVAD). RESULTS: Fifty-three patients were included with mean LVEF 18 ± 8% and majority in NYHA-class III-IV (79%). Median plasma somatostatin concentration was 18 pmol/L. In univariable regression analysis, log(somatostatin) was associated with increased central venous pressure (CVP; r2 = 0.14, p = 0.003) and a reduced cardiac index (CI; r2 = 0.15, p = 0.004). When adjusted for selected clinical variables (age, gender, LVEF, eGFR and BMI), log(somatostatin) remained a significant predictor of CVP (p = 0.044). Increased somatostatin concentrations predicted mortality in multivariable models (hazard ratio: 5.2 [1.2-22.2], p = 0.026) but not the combined endpoint of death, LVAD implantation or HTX. CONCLUSIONS: Somatostatin concentrations were associated with CVP and CI in patients with HF. The pathophysiological mechanism may be related to congestion and/or hypoperfusion of the intestine. Somatostatin was an independent predictor of mortality in advanced HF.

Clinical presentation and outcomes in women and men with advanced heart failure.

OBJECTIVE: To examine clinical characteristics and outcomes in women and men referred for advanced heart failure (HF) therapies such as left ventricular assist device (LVAD) or heart transplantation (HTx). Design: A retrospective study of 429 (23% women) consecutive adult HF patients not on inotropic or mechanical circulatory support with left ventricular ejection fraction ≤45% referred for assessment of advanced HF therapies at a single tertiary institution between 2002 and 2016. Clinical characteristics and outcomes were compared in women and men, and all patients underwent right heart catheterization (RHC). Results: At evaluation, women were younger than men (48 ± 13 vs. 51 ± 12 years, p = .02), and less likely to have ischemic cardiomyopathy. There were no significant differences in NYHA class, contemporary HF therapy use, or physical examination findings, except for lower jugular vein distension and body surface area in women. On RHC, women had lower cardiac filling pressures, but similar pulmonary vascular resistance and cardiac index. Peak oxygen uptake from cardiopulmonary exercise testing was similar in both sexes. At total follow-up time, there were 164 deaths (21% vs. 44%, p < .0001), 46 LVADs (3% vs. 13%, p = .005), 110 HTxs (32% vs. 25%, p = .15), and 82 HTxs without requiring LVAD (29% vs. 16%, p = .03) in women and men. The time from RHC to HTx (±LVAD) was significantly shorter in women compared to men. Female sex was significantly associated with higher survival independent of time-trend, age, and comorbidities. Conclusion: At evaluation, hemodynamics were less deranged in women. A higher proportion of women received HTx, their waitlist time was shorter, and survival greater.

Relationship between invasive hemodynamics and liver function in advanced heart failure.

Objective. To examine how liver function (LF) relates to invasive hemodynamics cross-sectionally and longitudinally, in advanced heart failure (AHF) patients treated with maximally tolerated medical HF therapy. Design. A retrospective study of 309 consecutive AHF patients with a left ventricular ejection fraction < 45% treated with maximally tolerated medical HF therapy who were referred for AHF therapies. All patients underwent right heart catheterization (RHC) using Swan-Ganz catheters. Cardiac output was measured using thermodilution. Measurements of pulmonary capillary wedge pressure (PCWP), central venous pressure (CVP), cardiac index (CI) and mean arterial pressure (MAP) were obtained. RHC and evaluation of LF were repeated (median (IQR) = 186.5 (150-208) days) in 33 patients. Results. Mean (SD) age was 50 (±13) years, and 239 (77%) were men. Only 22 (7%) were treated with inotropes, and none were receiving mechanical circulatory support. Median (IQR) plasma alanine transaminase (ALT) was 32 (22-53) U/l, alkaline phosphatase (ALP) 82 (63-122) U/l, bilirubin 14 (9-22) µmol/l, albumin 39 (35-43) g/l, lactate dehydrogenase 212 (175-275) U/l, and the prothrombin time/International Normalized Ratio (PT/INR) 1.1 (1.0-1.3). In multivariate analyses significant associations between LF tests and hemodynamics were seen for CVP: ALP (ß = 0.031, p = .0002), bilirubin (ß = 0.027, p = .004), and INR (ß = 0.013, p = .002). PCWP (ß = 0.020, p = .002) and CI (ß = -0.17, p = .005) were also associated with bilirubin. Over time, changes in bilirubin correlated positively with changes in CVP (ß = 1.496, p = .005). Conclusion. In optimally treated AHF patients, CVP was associated with both markers of biliary excretion and liver synthesis function, whereas changes in CVP were associated with changes in markers of biliary excretion. Decongestion may improve measures of LF in AHF.

Lung diffusion capacity in advanced heart failure: relation to central haemodynamics and outcome.

AIMS: Patients with heart failure (HF) are known to have a reduced pulmonary diffusion capacity for carbon monoxide (DLCO ), but little is known about how lung function relates to central haemodynamics. The aim of this study was to investigate the association between haemodynamic variables and pulmonary diffusion capacity adjusted for alveolar volume in congestive HF patients and to analyse how predicted DLCO /VA affects mortality in relation to the haemodynamic status. METHODS AND RESULTS: We retrospectively studied right heart catheterization (RHC) and lung function data on 262 HF patients (mean age 51 ± 13 years) with a left ventricular ejection fraction < 45% referred non-urgently for evaluation for heart transplantation (HTX) or left ventricular assist device (LVAD). Univariate and multivariate linear regression models were constructed to examine the associations between predicted values of DLCO /VA , forced vital capacity (FVC) and forced expiratory volume in 1 s (FEV1 ), and haemodynamic parameters [pulmonary capillary wedge pressure (PCWP), central venous pressure, cardiac index, mean pulmonary artery pressure, and mean arterial pressure] as well as other factors known to affect lung function in HF. FEV1 was reduced to <80% of predicted value in 55% of the population, and DLCO/ VA was reduced in 63% of the population. DLCO /VA correlated positively with pulmonary capillary wedge pressure in both univariate and multivariate analyses for all included patients (P < 0.001 and P = 0.045, respectively) and a restricted population of patients with the shortest time between RHC and lung function testing (P = 0.005, P = 0.015). DLCO /VA predicted mortality in multivariate models [hazard ratio 1.5 (1.1-2.1)] but not the combined endpoint of death, LVAD implantation, or HTX. There was no significant correlation between haemodynamics and predicted FVC or FEV1 . CONCLUSIONS: Pulmonary diffusion capacity correlates positively with left ventricular fillings pressures, and reduced values predict increased mortality in patients with HF. This might be driven by increased lung capillary volume in patients with pulmonary congestion.

Relation between invasive hemodynamics and measured glomerular filtration rate by 51Cr-EDTA clearance in advanced heart failure.

The interaction between hemodynamics and kidney function in heart failure (HF) is incompletely understood. We investigated the association between invasive hemodynamic parameters and measured glomerular filtration rate (mGFR) by plasma clearance of 51-chromium-labeled ethylenediamine tetra-acetic acid (51Cr-EDTA) in patients with advanced HF and tested the hypothesis that patients with reduced mGFR have lower cardiac index (CI) and mean arterial pressure (MAP) as well as higher central venous pressure (CVP) and pulmonary capillary wedge pressure (PCWP). We retrospectively studied 242 patients (mean age 50 ± 13 years) referred for evaluation for heart transplantation or implantation of a left ventricular assist device with a left ventricular ejection fraction < 45% on optimal medical therapy, who underwent right heart catheterization (RHC) and measurement of 51Cr-EDTA clearance. Mean mGFR was 63 ± 21 mL/min/1.73 m2, CI was 2.3 ± 0.7 L/min/m2, PCWP was 21 ± 9 mmHg, and CVP was 10.3 ± 5.2 mmHg. Univariate analysis demonstrated a significant correlation between mGFR and CI (r2 = 0.030, p = .007) and CVP (r2 = 0.017, p = .049) but not between mGFR and MAP or PCWP. In multivariate analyses, none of the hemodynamic variables remained significantly associated with mGFR. While CVP and CI were correlated with mGFR in univariate analysis the results of analyses adjusted for multiple covariates suggest that hemodynamics are only correlated to renal function in advanced HF to a modest degree challenging the hypothesis that renal dysfunction in HF mainly is a consequence of renal congestion.