Coronary perfusion pressure is associated with adverse outcomes in advanced heart failure.

BACKGROUND: Myocardial perfusion is an important determinant of cardiac function. We hypothesized that low coronary perfusion pressure (CPP) would be associated with adverse outcomes in heart failure. Myocardial perfusion impacts the contractile efficiency thus a low CPP would signal low myocardial perfusion in the face of increased cardiac demand as a result of volume overload. METHODS: We analyzed patients with complete hemodynamic data in the Evaluation Study of Congestive Heart Failure and Pulmonary Artery Catheterization Effectiveness trial using Cox Proportional Hazards regression for the primary outcome of the composite risk of death, heart transplantation, or left ventricular assist device [(LVAD). DT × LVAD] and the secondary outcome of the composite risk of DT × LVAD and heart failure hospitalization (DT × LVADHF). CPP was calculated as the difference between diastolic blood pressure and pulmonary artery wedge pressure. Heart failure categories (ischemic vs non-ischemic) were also stratified based on CPP strata. RESULTS: The 158 patients (56.7 ± 13.6 years, 28.5% female) studied had a median CPP of 40 mmHg (IQR 35-52 mmHg). During 6 months of follow-up, 35 (22.2%) had the composite primary outcome and 109 (69.0%) had the composite secondary outcome. When these outcomes were then stratified based on the median, CPP was associated with these outcomes. Increasing CPP was associated with lower risk of both the primary outcome of DT × LVAD (HR 0.96, 95% CI 0.94-0.99 p = .002) and as well as the secondary outcome of DT × LVADHF (p = .0008) There was significant interaction between CPP and ischemic etiology (p = .04). CONCLUSION: A low coronary artery perfusion pressure below (median) 40mmHg in patients with advanced heart failure undergoing invasive hemodynamic monitoring with a pulmonary artery catheter was associated with adverse outcomes. CPP could useful in guiding risk stratification of advanced heart failure patients and timely evaluation of advanced heart failure therapies.

Systemic arterial pulsatility index (SAPi) predicts adverse outcomes in advanced heart failure patients.

Ventriculo-arterial (VA) coupling has been shown to have physiologic importance in heart failure (HF). We hypothesized that the systemic arterial pulsatility index (SAPi), a measure that integrates pulse pressure and a proxy for left ventricular end-diastolic pressure, would be associated with adverse outcomes in advanced HF. We evaluated the SAPi ([systemic systolic blood pressure-systemic diastolic blood pressure]/pulmonary artery wedge pressure) obtained from the final hemodynamic measurement in patients randomized to therapy guided by a pulmonary arterial catheter (PAC) and with complete data in the Evaluation Study of Congestive Heart Failure and Pulmonary Artery Catheterization Effectiveness (ESCAPE) trial. Cox proportional hazards regression was performed for the outcomes of (a) death, transplant, left ventricular assist device (DTxLVAD) or hospitalization, (DTxLVADHF) and (b) DTxLVAD. Among 142 patients (mean age 56.8 ± 13.3 years, 30.3% female), the median SAPi was 2.57 (IQR 1.63-3.45). Increasing SAPi was associated with significant reductions in DTxLVAD (HR 0.60 per unit increase in SAPi, 95% CI 0.44-0.84) and DTxLVADHF (HR 0.81 per unit increase, 95% CI 0.70-0.95). Patients with a SAPi ≤ 2.57 had a marked increase in both outcomes, including more than twice the risk of DTxLVAD (HR 2.19, 95% CI 1.11-4.30) over 6 months. Among advanced heart failure patients with invasive hemodynamic monitoring in the ESCAPE trial, SAPi was strongly associated with adverse clinical outcomes. These findings support further investigation of the SAPi to guide treatment and prognosis in HF undergoing invasive hemodynamic monitoring.

MAGGIC, STS, and EuroSCORE II Risk Score Comparison After Aortic and Mitral Valve Surgery.

OBJECTIVES: To compare the Meta-Analysis Global Group in Chronic Heart Failure (MAGGIC) risk score with the established Society of Thoracic Surgeons (STS) and EuroSCORE II risk prediction models regarding mortality discrimination after aortic and mitral valve surgery. DESIGN: Retrospective cohort study. SETTING: Single tertiary academic medical center. PARTICIPANTS: A total of 259 patients who underwent open aortic valve replacement or open mitral valve repair/replacement from 2009-2014. INTERVENTIONS: Retrospective chart review. MEASUREMENTS AND MAIN RESULTS: MAGGIC, STS, and EuroSCORE II risk scores for each patient were studied using binary logistic regression and receiver operating characteristic analysis for the primary endpoint of one-year mortality and secondary endpoint of 30-day mortality. One-year mortality C-statistics were similar across risk scores (STS 0.709, 95% confidence interval [CI] 0.578-0.841; MAGGIC 0.673, 95% CI 0.547-0.799; EuroSCORE II 0.642, 95% CI 0.521-0.762; p = 0.56 between STS and MAGGIC; p = 0.20 between STS and EuroSCORE II; and p = 0.69 between MAGGIC and EuroSCORE II). Thirty-day mortality C-statistics also were similar between STS (0.797, 95% CI 0.655-0.939; p < 0.0001 v null hypothesis), MAGGIC (0.721, 95% CI 0.581-0.860; p = 0.33 v STS), and EuroSCORE II (0.688, 95% CI 0.557-0.818; p = 0.06 v STS; p = 0.68 v MAGGIC). CONCLUSIONS: The MAGGIC risk score performs similarly to STS and EuroSCORE II risk models in mortality discrimination after aortic and mitral valve surgery, albeit in a small sample size. This finding has important implications in establishing MAGGIC as a viable prognostic model in this population subset, with fewer variables and ease of use representing key advantages over STS and EuroSCORE II.

Racial/Ethnic and Gender Disparities in Heart Failure with Reduced Ejection Fraction.

PURPOSE OF REVIEW: This review highlights variability in prescribing of nonpharmacologic heart failure with reduced ejection fraction (HFrEF) therapies by race, ethnicity, and gender. The review also explores the evidence underlying these inequalities as well as potential mitigation strategies. RECENT FINDINGS: There have been major advances in HF therapies that have led to improved overall survival of HF patients. However, racial and ethnic groups of color and women have not received equitable access to these therapies. Patients of color and women are less likely to receive nonpharmacologic therapies for HFrEF than White patients and men. Therapies including exercise rehabilitation, percutaneous transcatheter mitral valve repair, cardiac resynchronization therapy, heart transplant, and ventricular assist devices all have proven efficacy in patients of color and women but remain underprescribed. Outcomes with most nonpharmacologic therapy are similar or better among patients of color and women than White patients and men. System-level changes are urgently needed to achieve equity in access to nonpharmacologic HFrEF therapies by race, ethnicity, and gender.

Pulmonary Artery Proportional Pulse Pressure (PAPP) Index Identifies Patients With Improved Survival From the CardioMEMS Implantable Pulmonary Artery Pressure Monitor.

BACKGROUND: Pulmonary artery proportional pulse pressure (PAPP) was recently shown to have prognostic value in heart failure (HF) with reduced ejection fraction (HFrEF) and pulmonary hypertension. We tested the hypothesis that PAPP would be predictive of adverse outcomes in patients with implantable pulmonary artery pressure monitor (CardioMEMS™ HF System, St. Jude Medical [now Abbott], Atlanta, GA, USA). METHODS: Survival analysis with Cox proportional hazards regression was used to evaluate all-cause deaths and HF hospitalisation (HFH) in CHAMPION trial1 patients who received treatment with the CardioMEMS device based on the PAPP. RESULTS: Among 550 randomised patients, 274 had PAPP ≤ the median value of 0.583 while 276 had PAPP>0.583. Patients with PAPP≤0.583 (versus PAPP>0.583) had an increased risk of HFH (HR 1.40, 95% CI 1.16-1.68, p=0.0004) and experienced a significant 46% reduction in annualised risk of death with CardioMEMS treatment (HR 0.54, 95% CI 0.31-0.92) during 2-3 years of follow-up. This survival benefit was attributable to the treatment benefit in patients with HFrEF and PAPP≤0.583 (HR 0.50, 95% CI 0.28-0.90, p<0.05). Patients with PAPP>0.583 or HF with preserved EF (HFpEF) had no significant survival benefit with treatment (p>0.05). CONCLUSION: Lower PAPP in HFrEF patients with CardioMEMS constitutes a higher mortality risk status. More studies are needed to understand clinical applications of PAPP in implantable pulmonary artery pressure monitors.

Haemodynamically Derived Pulmonary Artery Pulsatility Index Predicts Mortality in Pulmonary Arterial Hypertension.

BACKGROUND: Pulmonary artery (PA) pulsitility index (PAPi) is a novel haemodynamic index shown to predict right ventricular failure in acute inferior myocardial infarction and post left ventricular assist device surgery. We hypothesised that PAPi calculated as [PA systolic pressure - PA diastolic pressure]/right atrial pressure (RAP) would be associated with mortality in the National Institutes of Health Registry for Primary Pulmonary Hypertension (NIH-RPPH). METHODS: The impact of PAPi, the Pulmonary Hypertension Connection (PHC) risk score, right ventricular stroke work, pulmonary artery capacitance (PAC), other haemodynamic indices, and demographic characteristics was evaluated in 272 NIH-RPPH patients using multivariable Cox proportional hazards (CPH) regression and receiver operating characteristic (ROC) analysis. RESULTS: In the 272 patients (median age 37.7+/-15.9years, 63% female), the median PAPi was 5.8 (IQR 3.7-9.2). During 5years of follow-up, 51.8% of the patients died. Survival was markedly lower (32.8% during the first 3years) in PAPi quartile 1 compared with the remaining patients (58.5% over 3years in quartiles 2-4; p<0.0001). The best multivariable CPH survival model included PAPi, the PHC-Risk score, PAC, and body mass index (BMI). In this model, the adjusted hazard ratio for death with increasing PAPi was 0.946 (95% CI 0.905-0.989). The independent ROC areas for 5-year survival based on bivariable logistic regression for PAPi, BMI, PHC Risk, and PAC were 0.63, 0.62, 0.64, and 0.65, respectively (p<0.01). The ROC area for 5-year survival for the multivariable logistic model with all four covariates was 0.77 (p<0.0001). CONCLUSIONS: Pulmonary artery pulsatility index was independently associated with survival in PAH, highlighting the utility of PAPi in combination with other key measures for risk stratification in this population.

Increased Pulmonary-Systemic Pulse Pressure Ratio Is Associated With Increased Mortality in Group 1 Pulmonary Hypertension.

BACKGROUND: Pulmonary arterial hypertension (PAH) is characterised by remodelling of the pulmonary vasculature leading to right ventricular (RV) failure. The failing RV, through interventricular uncoupling, deleteriously impacts the left ventricle and overall cardiac efficiency. We hypothesised that the ratio of the pulmonary artery pulse pressure to the systemic pulse pressure ("pulmonary-systemic pulse pressure ratio", or PS-PPR) would be associated with mortality in PAH. METHODS: We conducted a retrospective analysis of 262 patients in the National Institute of Health Primary Pulmonary Hypertension Registry (NIH-PPH). We evaluated the association between the PS-PPR and mortality after adjustment for the Pulmonary Hypertension Connection (PHC) risk equation. RESULTS: Among 262 patients (mean age 37.5±15.8years, 62.2% female), median PS-PPR was 1.04 (IQR 0.79-1.30). In the Cox proportional hazards regression model, each one unit increase in the PS-PPR was associated with more than a two-fold increase in mortality during follow-up (HR 2.06, 95% CI 1.40-3.02, p=0.0002), and this association of PS-PPR with mortality remained significant in the multivariable Cox model adjusted for the PHC risk equation, mean pulmonary artery pressure, and body mass index (BMI) (adjusted HR 1.81, 95% CI 1.13-2.88, p=0.01). Furthermore, PS-PPR in the upper quartile (>1.30) versus quartiles 1-3 was associated with a 68% increase in mortality after adjustment for these same covariates (adjusted HR 1.68, 95% CI 1.13-2.50, p=0.01). CONCLUSIONS: Pulmonary-systemic pulse pressure ratio, a marker of biventricular efficiency, is associated with survival in PAH even after adjustment for the PHC risk equation. Further studies are needed on the wider applications of PS-PPR in PAH patients.

Right atrial to left atrial volume index ratio is associated with increased mortality in patients with pulmonary hypertension.

BACKGROUND: Pulmonary hypertension (PH) is characterized by increased pulmonary vascular resistance leading to right heart failure. Elevated right atrial (RA) pressure reflects right ventricular (RV) pressure overload and is an established risk factor for mortality in PH. We hypothesized that PH patients with an increased ratio of RA to LA volume index (RAVI/LAVI), would have increased mortality. METHODS: We evaluated the association of RAVI/LAVI with mortality in 124 patients seen at a single academic center's PH clinic after adjusting for the REVEAL risk score, an established risk score in PH. LA and RA volume indices were measured in the four-and two-chamber views by two independent researchers. Multivariable logistic regression was used to model the independent association of RAVI/LAVI with survival. RESULTS: Among 124 patients (mean age 62 ± 12.7 years, 68.6% female), each unit increase in RAVI/LAVI was associated with a nearly twofold increase in mortality (OR: 1.91, 95% CI: 1.20-3.04). In a multivariable logistic regression, each unit increase in RAVI/LAVI was associated with a nearly twofold increase in mortality (OR: 1.73, 95% CI: 1.003-2.998). Furthermore, RAVI/LAVI in the highest quartile (>1.42) was significantly associated with elevated right atrial pressure (RAP) to pulmonary artery wedge pressure ratio (RAP/PAWP) (0.76 ± 0.41, P = 0.02) compared with the lowest quartile (<0.77), suggesting an interaction between invasive hemodynamic data, atrial structural changes, and mortality in PH. CONCLUSIONS: Increased RAVI/LAVI in PH is associated with decreased survival and accounts for atrial structural remodeling related to invasive hemodynamics. These findings support further study of this index in predicting outcomes in PH.

Unprovoked Venous Thromboembolism: The Search for the Cause.

Venous thromboembolism (VTE) is a common vascular disorder encompassing deep vein thrombosis (DVT) and pulmonary embolism (PE). There is no data on global estimates of VTE prevalence and incidence. Most patients with unprovoked VTE require secondary thromboprophylaxis upon the completion of the primary treatment phase if they have no high bleeding risk. Risk prediction models can help identify patients at low VTE recurrence risk who may discontinue anticoagulation upon the completion of the primary treatment phase.

Sex, Racial, and Geographic Disparities in Pulmonary Embolism-related Mortality Nationwide.

Rationale: Acute pulmonary embolism is a leading cause of cardiovascular death. There are limited data on the national mortality trends from pulmonary embolism. Understanding these trends is crucial for addressing the mortality and associated disparities associated with pulmonary embolism. Objectives: To analyze the national mortality trends related to acute pulmonary embolism and determine the overall age-adjusted mortality rate (AAMR) per 100,000 population for the study period and assess changes in AAMR among different sexes, races, and geographic locations. Methods: We conducted a retrospective cohort analysis using mortality data of individuals aged ⩾15 years with pulmonary embolism listed as the underlying cause of death in the Centers for Disease Control and Prevention Wide-Ranging Online Data for Epidemiologic Research database from January 2006 to December 2019. These data are produced by the National Center for Health Statistics. Results: A total of 109,992 pulmonary embolism-related deaths were noted in this dataset nationwide between 2006 and 2019. Of these, women constituted 60,113 (54.7%). The AAMR per 100,000 was not significantly changed, from 2.84 in 2006 to 2.81 in 2019 (average annual percentage change [AAPC], 0.2; 95% confidence interval [CI], -0.1 to 0.5; P = 0.15). AAMR increased for men throughout the study period compared with women (AAPC, 0.7 for men; 95% CI, 0.3 to 1.2; P = 0.004 vs. AAPC, -0.4 for women; 95% CI, -1.1 to 0.3; P = 0.23, respectively). Similarly, AAMR for pulmonary embolism increased for Black compared with White individuals, from 5.18 to 5.26 (AAPC, 0.4; 95% CI, 0.0 to 0.7; P = 0.05) and 2.82 to 2.86 (AAPC, 0.0; 95% CI, -0.6 to 0.6; P = 0.99), respectively. Similarly, AAMR for pulmonary embolism was higher in rural areas than in micropolitan and large metropolitan areas during the study period (4.07 [95% CI, 4.02 to 4.12] vs. 3.24 [95% CI, 3.21 to 3.27] vs. 2.32 [95% CI, 2.30-2.34], respectively). Conclusions: Pulmonary embolism mortality remains high and unchanged over the past decade, and enduring sex, racial and socioeconomic disparities persist in pulmonary embolism. Targeted efforts to decrease pulmonary embolism mortality and address such disparities are needed.

Association Between the Affordable Care Act Medicaid Expansion and Receipt of Cardiac Resynchronization Therapy by Race and Ethnicity.

Background Black and Hispanic patients are less likely to receive cardiac resynchronization therapy (CRT) than White patients. Medicaid expansion has been associated with increased access to cardiovascular care among racial and ethnic groups with higher prevalence of underinsurance. It is unknown whether the Medicaid expansion was associated with increased receipt of CRT by race and ethnicity. Methods and Results Using Healthcare Cost and Utilization Project Data State Inpatient Databases from 19 states and Washington, DC, we analyzed 1061 patients from early-adopter states (Medicaid expansion by January 2014) and 745 patients from nonadopter states (no implementation 2013-2014). Estimates of change in census-adjusted rates of CRT with or without defibrillator by race and ethnicity and Medicaid adopter status 1 year before and after January 2014 were conducted using a quasi-Poisson regression model. Following the Medicaid expansion, the rate of CRT did not significantly change among Black individuals from early-adopter states (1.07 [95% CI, 0.78-1.48]) or nonadopter states (0.79 [95% CI, 0.57-1.09]). There were no significant changes in rates of CRT among Hispanic individuals from early-adopter states (0.99 [95% CI, 0.70-1.38]) or nonadopter states (1.01 [95% CI, 0.65-1.57]). There was a 34% increase in CRT rates among White individuals from early-adopter states (1.34 [95% CI, 1.05-1.70]), and no significant change among White individuals from nonadopter states (0.77 [95% CI, 0.59-1.02]). The change in CRT rates among White individuals was associated with the timing of the Medicaid implementation (P=0.003). Conclusions Among states participating in Healthcare Cost and Utilization Project Data State Inpatient Databases, implementation of Medicaid expansion was associated with increase in CRT rates among White individuals residing in states that adopted the Medicaid expansion policy. Further work is needed to address disparities in CRT among Black and Hispanic patients.

Right atrial volume index to left atrial volume index ratio is associated with adverse clinical outcomes in cardiogenic shock.

BACKGROUND: Structural remodeling in chronic systolic heart failure (HF) is associated with neurohormonal and hemodynamic perturbations among HF patients presenting with cardiogenic shock (CS) and HF. Our objective was to test the hypothesis was that atrial remodeling marked by an increased right atrial volume index (RAVI) to left atrial volume index (LAVI) ratio is associated with adverse clinical outcomes in CS. METHODS: Patients in this cohort were admitted to the intensive care unit with evidence of congestion (pulmonary capillary wedge pressure > 15) and cardiogenic shock (cardiac index < 2.2, systolic blood pressure < 90 mmHg, and clinical evidence supporting CS) and had an echocardiogram at the time of admission. RAVI was measured using Simpson's method in the apical four-chamber view, while LAVI was measured using the biplane disc summation method in the four and two-chamber views by two independent observers. Cox proportional hazards regression analysis was used to assess the association of RAVI-LAVI with the combined outcome of death or left ventricular assist device (LVAD). RESULTS: Among 113 patients (mean age 59 ± 14.9 years, 29.2% female), median RAVI/LAVI was 0.84. During a median follow-up of 12 months, 43 patients died, and 65 patients had the combined outcomes of death or LVAD. Patients with RAVI/LAVI ratio above the median had a greater incidence of death or LVAD (Log-rank p ≤ 0.001), and increasing RAVI/LAVI was significantly associated with the outcomes of death or LVAD (HR 1.71 95% CI 1.11-2.64, chi square 5.91, p = 0.010) even after adjustment for patient characteristics, echocardiographic and hemodynamic variables. CONCLUSION: RAVI/LAVI is an easily assessed novel echocardiographic parameter strongly associated with the survival and or the need for mechanical circulatory support in patients with CS.

Decreased pulmonary arterial proportional pulse pressure is associated with increased mortality in group 1 pulmonary hypertension.

BACKGROUND: This study evaluated the utility of a novel index, pulmonary arterial (PA) proportional pulse pressure (PAPP; range 0-1, defined as [PA systolic pressure - PA diastolic pressure] / PA systolic pressure), in predicting mortality in patients with World Health Organization group 1 pulmonary hypertension (PH). HYPOTHESIS: Low PAPP is associated with increased 5-year mortality independent of a validated contemporary risk-prediction equation (Pulmonary Hypertension Connection [PHC] equation). METHODS: In a group of 262 patients in the National Institutes of Health Primary Pulmonary Hypertension (NIH-PPH) Registry, PAPP and the PHC risk equation were used to predict mortality during 5 years of follow-up using Cox proportional hazards models. Kaplan-Meier survival curves were used to compare mortality among PAPP quartiles, and significance was tested using the log-rank test. RESULTS: Patients in the lowest quartile (PAPP ≤0.47) had a significantly higher 5-year mortality than did patients in higher quartiles (log-rank P = 0.016). In a Cox model adjusted for the PHC equation, PAPP remained significantly associated with 5-year mortality (hazard ratio: 0.74 per 0.10 increase in PAPP, 95% confidence interval: 0.61-0.90). The χ2 statistic for the single PAPP covariate in this model was 8.8 (P = 0.003), which compared favorably with the χ2 statistic of 15.2 (P < 0.0001) for the multivariable PHC equation. CONCLUSIONS: PAPP, an index of ventricular-arterial coupling, is independently associated with survival in World Health Organization group 1 PH. The use of this easily measurable index for guiding risk stratification needs further investigation.

Plasma Volume and Renal Function Predict Six-Month Survival after Hospitalization for Acute Decompensated Heart Failure.

BACKGROUND: Plasma volume (PV) is contracted in stable patients with heart failure (HF) due to decongestion strategies. On the other hand, increased PV can adversely affect the trajectory of HF. We therefore examined the effects of increased percentage change in PV (%ΔPV), blood urea nitrogen (BUN), and %ΔPV stratified by BUN and glomerular filtration rate (GFR) on survival after discharge in patients hospitalized for acute decompensated HF (ADHF). METHODS: We used the Strauss-Davis-Rosenbaum formula to calculate the %ΔPV between baseline and hospital discharge in a cohort from the Evaluation Study of Congestive Heart Failure and Pulmonary Artery Catheterization Effectiveness trial (ESCAPE). Kaplan-Meier curves were constructed for survival over 6 months. Cox proportional hazards regression was used to obtain adjusted hazard ratios (HR) and 95% confidence intervals (95% CI) for the associations between survival after discharge and %ΔPV, BUN, and %ΔPV stratified by BUN and GFR. RESULTS: Of the 324 patients included in our study (age 56.1 ± 13.6 years, 26.5% female), those with increased or no %ΔPV at discharge were less likely to survive at 6 months compared with those having reduced %ΔPV (log rank, p = 0.0093). Increased %ΔPV (HR 1.08 per 10% increase; 95% CI: 1.02-1.14) and increased BUN at discharge (HR 1.02 per mg/dL; 95% CI: 1.01-1.03) were independently associated with worse survival. Decreasing %ΔPV had a greater association with improved survival in patients with discharge BUN <31 mg/dL (p = 0.02) and discharge GFR >40 mL/min/1.73 m2 (p = 0.047). CONCLUSIONS: Increased %ΔPV and BUN at discharge predicted worse 6-month survival in patients with ADHF. Decreased %ΔPV with low BUN or high GFR at discharge was associated with improved survival.