Cost Effectiveness of Dapagliflozin for Heart Failure Across the Spectrum of Ejection Fraction: An Economic Evaluation Based on Pooled, Individual Participant Data From the DELIVER and DAPA-HF Trials.

BACKGROUND: The sodium glucose cotransporter-2 inhibitors are guideline-recommended to treat heart failure across the spectrum of left ventricular ejection fraction; however, economic evaluations of adding sodium glucose cotransporter-2 inhibitors to standard of care in chronic heart failure across a broad left ventricular ejection fraction range are lacking. METHODS AND RESULTS: We conducted a US-based cost-effectiveness analysis of dapagliflozin added to standard of care in a chronic heart failure population using pooled, participant data from the DAPA-HF (Dapagliflozin and Prevention of Adverse Outcomes in Heart Failure) and DELIVER (Dapagliflozin Evaluation to Improve the Lives of Patients With Preserved Ejection Fraction Heart Failure) trials. The 3-state Markov model used estimates of transitional probabilities, effectiveness of dapagliflozin, and utilities from the pooled trials. Costs estimates were obtained from published sources, including published rebates in dapagliflozin cost. Adding dapagliflozin to standard of care was estimated to produce an additional 0.53 quality-adjusted life years (QALYs) compared with standard of care alone. Incremental cost effectiveness ratios were $85 554/QALY when using the publicly reported full (undiscounted) Medicare cost ($515/month) and $40 081/QALY, at a published nearly 50% rebate ($263/month). The addition of dapagliflozin to standard of care would be of at least intermediate value (<$150 000/QALY) at a cost of <$872.58/month, of high value (<$50 000/QALY) at <$317.66/month, and cost saving at <$40.25/month. Dapagliflozin was of at least intermediate value in 92% of simulations when using the full (undiscounted) Medicare list cost in probabilistic sensitivity analyses. Cost effectiveness was most sensitive to the dapagliflozin cost and the effect on cardiovascular death. CONCLUSIONS: The addition of dapagliflozin to standard of care in patients with heart failure across the spectrum of ejection fraction was at least of intermediate value at the undiscounted Medicare cost and may be potentially of higher value on the basis of the level of discount, rebates, and price negotiations offered. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifiers: NCT01035255 & NCT01920711.

Health and Economic Evaluation of Sacubitril-Valsartan for Heart Failure Management.

Importance: The US Food and Drug Administration expanded labeling of sacubitril-valsartan from the treatment of patients with chronic heart failure (HF) with reduced ejection fraction (EF) to all patients with HF, noting the greatest benefits in those with below-normal EF. However, the upper bound of below normal is not clearly defined, and value determinations across a broader EF range are unknown. Objective: To estimate the cost-effectiveness of sacubitril-valsartan vs renin-angiotensin system inhibitors (RASis) across various upper-level cutoffs of EF. Design, Setting, and Participants: This economic evaluation included participant-level data from the PARADIGM-HF (Prospective Comparison of ARNI With ACEI to Determine Impact on Global Mortality and Morbidity in Heart Failure) and the PARAGON-HF (Prospective Comparison of ARNi with ARB Global Outcomes in HF With Preserved Ejection Fraction) trials. PARADIGM-HF was conducted between 2009 and 2014, PARAGON-HF was conducted between 2014 and 2019, and this analysis was conducted between 2021 and 2023. Main Outcomes and Measures: A 5-state Markov model used risk reductions for all-cause mortality and HF hospitalization from PARADIGM-HF and PARAGON-HF. Quality-of-life differences were estimated from EuroQol-5D scores. Hospitalization and medication costs were obtained from published national sources; the wholesale acquisition cost of sacubitril-valsartan was $7092 per year. Risk estimates and treatment effects were generated in consecutive 5% EF increments up to 60% and applied to an EF distribution of US patients with HF from the Get With the Guidelines-Heart Failure registry. The base case included a lifetime horizon from a health care sector perspective. Incremental cost-effectiveness ratios (ICERs) were estimated at EFs of 60% or less (base case) and at various upper-level EF cutoffs. Results: Among 13 264 total patients whose data were analyzed, for those with EFs of 60% or less, sacubitril-valsartan was projected to add 0.53 quality-adjusted life-years (QALYs) at an incremental lifetime cost of $40 892 compared with RASi, yielding an ICER of $76 852 per QALY. In a probabilistic sensitivity analysis, 95% of the values of the ICER occurred between $71 516 and $82 970 per QALY. Among patients with chronic HF and an EF of 60% or less, treatment with sacubitril-valsartan vs RASis would be at least of economic intermediate value (ICER <$180 000 per QALY) at a sacubitril-valsartan cost of $10 242 or less per year, of high economic value (ICER <$60 000 per QALY) at a cost of $3673 or less per year, and cost-saving at a cost of $338 or less per year. The ICERs were $67 331 per QALY, $59 614 per QALY, and $56 786 per QALY at EFs of 55% or less, 50% or less, and 45% or less, respectively. Treatment with sacubitril-valsartan in only those with EFs of 45% or greater (up to ≤60%) yielded an ICER of $127 172 per QALY gained; treatment was more cost-effective in those at the lower end of this range (ICER of $100 388 per QALY gained for those with EFs of 45%-55%; ICER of $84 291 per QALY gained for those with EFs of 45%-50%). Conclusions and Relevance: Cost-effectiveness modeling provided an ICER for treatment with sacubitril-valsartan vs RASis consistent with high economic value for patients with reduced and mildly reduced EFs (≤50%) and at least intermediate value at the current undiscounted wholesale acquisition cost price at an EF of 60% or less. Treatment was more cost-effective at lower EF ranges. These findings may have implications for coverage decisions and value assessments in contemporary clinical practice guidelines.

Racial Differences and Temporal Obesity Trends in Heart Failure with Preserved Ejection Fraction.

BACKGROUND/OBJECTIVES: Obesity increases with age, is disproportionately prevalent in black populations, and is associated with heart failure with preserved ejection fraction (HFpEF). An "obesity paradox," or improved survival with obesity, has been reported in patients with HFpEF. The aim of this study was to examine whether racial differences exist in the temporal trends and outcomes associated with obesity among older patients with HFpEF. DESIGN: Community surveillance of acute decompensated heart failure (ADHF) hospitalizations, sampled by stratified design from 2005 to 2014. SETTING: Atherosclerosis Risk in Communities Study (NC, MS, MD, MN). PARTICIPANTS: A total of 10,147 weighted hospitalizations for ADHF (64% female, 74% white, mean age 77 years), with ejection fraction ≥50%. MEASUREMENTS: ADHF classified by physician review, HFpEF defined by ejection fraction ≥50%. Body mass index (BMI) calculated from weight at hospital discharge. Obesity defined by BMI ≥30 kg/m2 , class III obesity by BMI ≥40 kg/m2 . RESULTS: When aggregated across 2005-2014, the mean BMI was higher for black compared to white patients (34 vs 30 kg/m2 ; P < .0001), as was prevalence of obesity (56% vs 43%; P < .0001) and class III obesity (24% vs 13%; P < .0001). Over time, the annual mean BMI and prevalence of class III obesity remained stable for black patients, but steadily increased for white patients, with annual rates statistically differing by race (P-interaction = .04 and P = .03, respectively). For both races, a U-shaped adjusted mortality risk was observed across BMI categories, with the highest risk among patients with a BMI ≥40 kg/m2 . CONCLUSION: Black patients were disproportionately burdened by obesity in this decade-long community surveillance of older hospitalized patients with HFpEF. However, temporal increases in mean BMI and class III obesity prevalence among white patients narrowed the racial difference in recent years. For both races, the worst survival was observed with class III obesity. Effective strategies are needed to manage obesity in patients with HFpEF.

Application of Guideline-Based Echocardiographic Assessment of Left Atrial Pressure to Heart Failure with Preserved Ejection Fraction.

BACKGROUND: Early, noninvasive identification of patients with heart failure with preserved ejection fraction (HFpEF) with congestion may allow timely tailoring of decongestive therapies. The 2016 American Society of Echocardiography and European Association of Cardiovascular Imaging guidelines provide an algorithm to assess for elevated left atrial pressure (LAP); the associations of echocardiographic LAP with clinical status and disease progression in patients with HFpEF are unclear. METHODS: Participants in the Phosphodiesterase-5 Inhibition to Improve Clinical Status and Exercise Capacity in HFpEF trial were categorized into one of four prespecified guideline-based echocardiographic LAP categories: (1) normal, (2) elevated, (3) atrial fibrillation (AF) at the time of echocardiography, or (4) indeterminate. Associations of echocardiographic LAP categories with baseline exercise capacity, change in exercise capacity, and change in N-terminal pro-B-type natriuretic peptide over 24 weeks were evaluated. RESULTS: Of 216 participants, 199 underwent mitral inflow Doppler echocardiography for LAP categorization. Participants with elevated echocardiographic LAP (n = 81) or AF (n = 57) were older and had a higher prevalence of kidney dysfunction. Compared with the normal echocardiographic LAP group (n = 28), elevated echocardiographic LAP and AF were each independently associated with a greater reduction in peak oxygen consumption over 24 weeks after adjusting for baseline values and clinical covariates (ß for elevated echocardiographic LAP = -1.55 [95% CI, -2.59 to -0.51], P = .004; ß for AF = -1.33 [95% CI, -2.49 to -0.17], P = .03). Indeterminate echocardiographic LAP (n = 33) was also independently associated with a reduction in exercise capacity at 24 weeks compared with normal echocardiographic LAP (ß = -1.35; 95% CI, -2.51 to -0.19; P = .02). Finally, elevated echocardiographic LAP and AF were significantly associated with increases in N-terminal pro-B-type natriuretic peptide over 24 weeks compared with normal echocardiographic LAP. CONCLUSIONS: In patients with chronic HFpEF, elevated echocardiographic LAP and indeterminate echocardiographic LAP, as defined by contemporary guidelines, and AF were each independently associated with a reduction in exercise capacity compared with normal echocardiographic LAP. These findings suggest the potential utility of noninvasive LAP assessment in patients with HFpEF for tailoring treatments that decrease congestion.

Predictive Accuracy of Heart Failure-Specific Risk Equations in an Electronic Health Record-Based Cohort.

BACKGROUND: Guidelines recommend identification of individuals at risk for heart failure (HF). However, implementation of risk-based prevention strategies requires validation of HF-specific risk scores in diverse, real-world cohorts. Therefore, our objective was to assess the predictive accuracy of the Pooled Cohort Equations to Prevent HF within a primary prevention cohort derived from the electronic health record. METHODS: We retrospectively identified patients between the ages of 30 to 79 years in a multi-center integrated healthcare system, free of cardiovascular disease, with available data on HF risk factors, and at least 5 years of follow-up. We applied the Pooled Cohort Equations to Prevent HF tool to calculate sex and race-specific 5-year HF risk estimates. Incident HF was defined by the International Classification of Diseases codes. We assessed model discrimination and calibration, comparing predicted and observed rates for incident HF. RESULTS: Among 31 256 eligible adults, mean age was 51.4 years, 57% were women and 11% Black. Incident HF occurred in 568 patients (1.8%) over 5-year follow-up. The modified Pooled Cohort Equations to Prevent HF model for 5-year risk prediction of HF had excellent discrimination in White men (C-statistic 0.82 [95% CI, 0.79-0.86]) and women (0.82 [0.78-0.87]) and adequate discrimination in Black men (0.69 [0.60-0.78]) and women (0.69 [0.52-0.76]). Calibration was fair in all race-sex subgroups (χ2<20). CONCLUSIONS: A novel sex- and race-specific risk score predicts incident HF in a real-world, electronic health record-based cohort. Integration of HF risk into the electronic health record may allow for risk-based discussion, enhanced surveillance, and targeted preventive interventions to reduce the public health burden of HF.

The Upcoming Epidemic of Heart Failure in South Asia.

Currently, South Asia accounts for a quarter of the world population, yet it already claims ≈60% of the global burden of heart disease. Besides the epidemics of type 2 diabetes mellitus and coronary heart disease already faced by South Asian countries, recent studies suggest that South Asians may also be at an increased risk of heart failure (HF), and that it presents at earlier ages than in most other racial/ethnic groups. Although a frequently underrecognized threat, an eventual HF epidemic in the densely populated South Asian nations could have dramatic health, social and economic consequences, and urgent interventions are needed to flatten the curve of HF in South Asia. In this review, we discuss recent studies portraying these trends, and describe the mechanisms that may explain an increased risk of premature HF in South Asians compared with other groups, with a special focus on highly relevant features in South Asian populations including premature coronary heart disease, early type 2 diabetes mellitus, ubiquitous abdominal obesity, exposure to the world's highest levels of air pollution, highly prevalent pretransition forms of HF such as rheumatic heart disease, and underdevelopment of healthcare systems. Other rising lifestyle-related risk factors such as use of tobacco products, hypertension, and general obesity are also discussed. We evaluate the prognosis of HF in South Asian countries and the implications of an anticipated HF epidemic. Finally, we discuss proposed interventions aimed at curbing these adverse trends, management approaches that can improve the prognosis of prevalent HF in South Asian countries, and research gaps in this important field.

Temporal Trends in Prevalence and Prognostic Implications of Comorbidities Among Patients With Acute Decompensated Heart Failure: The ARIC Study Community Surveillance.

BACKGROUND: Patients with heart failure (HF) have multiple coexisting comorbidities. The temporal trends in the burden of comorbidities and associated risk of mortality among patients with HF with preserved ejection fraction (HFpEF) and HF with reduced ejection fraction (HFrEF) are not well established. METHODS: HF-related hospitalizations were sampled by stratified design from 4 US areas in 2005 to 2014 by the community surveillance component of the ARIC study (Atherosclerosis Risk in Communities). Acute decompensated HF was classified by standardized physician review and a previously validated algorithm. An ejection fraction <50% was considered HFrEF. A total of 15 comorbidities were abstracted from the medical record. Mortality outcomes were ascertained for up to 1-year postadmission by linking hospital records with death files. RESULTS: A total of 5460 hospitalizations (24 937 weighted hospitalizations) classified as acute decompensated HF had available ejection fraction data (53% female, 68% white, 53% HFrEF, 47% HFpEF). The average number of comorbidities was higher for patients with HFpEF versus HFrEF, both for women (5.53 versus 4.94; P<0.0001) and men (5.20 versus 4.82; P<0.0001). There was a significant temporal increase in the overall burden of comorbidities, both for patients with HFpEF (women: 5.17 in 2005-2009 to 5.87 in 2010-2013; men: 4.94 in 2005-2009 and 5.45 in 2010-2013) and HFrEF (women: 4.78 in 2005-2009 to 5.14 in 2010-2013; men: 4.62 in 2005-2009 and 5.06 in 2010-2013; P-trend<0.0001 for all). Higher comorbidity burden was significantly associated with higher adjusted risk of 1-year mortality, with a stronger association noted for HFpEF (hazard ratio [HR] per 1 higher comorbidity, 1.19 [95% CI, 1.14-1.25] versus HFrEF (HR, 1.10 [95% CI, 1.05-1.14]; P for interaction by HF type=0.02). The associated mortality risk per 1 higher comorbidity also increased significantly over time for patients with HFpEF and HFrEF, as well (P for interaction with time=0.002 and 0.02, respectively) Conclusions: The burden of comorbidities among hospitalized patients with acute decompensated HFpEF and HFrEF has increased over time, as has its associated mortality risk. Higher burden of comorbidities is associated with higher risk of mortality, with a stronger association noted among patients with HFpEF versus HFrEF.

Cost-Effectiveness of Tafamidis Therapy for Transthyretin Amyloid Cardiomyopathy.

BACKGROUND: In patients with transthyretin amyloid cardiomyopathy, tafamidis reduces all-cause mortality and cardiovascular hospitalizations and slows decline in quality of life compared with placebo. In May 2019, tafamidis received expedited approval from the US Food and Drug Administration as a breakthrough drug for a rare disease. However, at $225 000 per year, it is the most expensive cardiovascular drug ever launched in the United States, and its long-term cost-effectiveness and budget impact are uncertain. We therefore aimed to estimate the cost-effectiveness of tafamidis and its potential effect on US health care spending. METHODS: We developed a Markov model of patients with wild-type or variant transthyretin amyloid cardiomyopathy and heart failure (mean age, 74.5 years) using inputs from the ATTR-ACT trial (Transthyretin Amyloidosis Cardiomyopathy Clinical Trial), published literature, US Food and Drug Administration review documents, healthcare claims, and national survey data. We compared no disease-specific treatment ("usual care") with tafamidis therapy. The model reproduced 30-month survival, quality of life, and cardiovascular hospitalization rates observed in ATTR-ACT; future projections used a parametric survival model in the control arm, with constant hazards reduction in the tafamidis arm. We discounted future costs and quality-adjusted life-years by 3% annually and examined key parameter uncertainty using deterministic and probabilistic sensitivity analyses. The main outcomes were lifetime incremental cost-effectiveness ratio and annual budget impact, assessed from the US healthcare sector perspective. This study was independent of the ATTR-ACT trial sponsor. RESULTS: Compared with usual care, tafamidis was projected to add 1.29 (95% uncertainty interval, 0.47-1.75) quality-adjusted life-years at an incremental cost of $1 135 000 (872 000-1 377 000), resulting in an incremental cost-effectiveness ratio of $880 000 (697 000-1 564 000) per quality-adjusted life-year gained. Assuming a threshold of $100 000 per quality-adjusted life-year gained and current drug price, tafamidis was cost-effective in 0% of 10 000 probabilistic simulations. A 92.6% price reduction from $225 000 to $16 563 would be necessary to make tafamidis cost-effective at $100 000/quality-adjusted life-year. Results were sensitive to assumptions related to long-term effectiveness of tafamidis. Treating all eligible patients with transthyretin amyloid cardiomyopathy in the United States with tafamidis (n=120 000) was estimated to increase annual healthcare spending by $32.3 billion. CONCLUSIONS: Treatment with tafamidis is projected to produce substantial clinical benefit but would greatly exceed conventional cost-effectiveness thresholds at the current US list price. On the basis of recent US experience with high-cost cardiovascular medications, access to and uptake of this effective therapy may be limited unless there is a large reduction in drug costs.

Assessment of Predictors of Left Atrial Volume Response to a Transcatheter InterAtrial Shunt Device (from the REDUCE LAP-HF Trial).

In patients with heart failure and preserved or mildly reduced ejection fractions (EF ≥40%), implantation of an interatrial shunt device (IASD) resulted in heterogenous changes of the left atrial (LA) volume. Baseline characteristics that correlate with a favorable decrease in LA volume are unknown. We hypothesized that a larger ratio of left to right atrial volume at baseline would correlate strongly with LA volume decongestion following IASD implantation. Reduce Elevated LA Pressure in Patients With Heart Failure was a multicenter study of the safety and feasibility of IASD implantation. Sixty-four patients with EF ≥40% underwent device implantation along with baseline conventional echocardiograms, speckle tracking echocardiography, and resting and exercise hemodynamics. Higher LA compliance (-4.2%, p = 0.048) and right atrial reservoir strain (-0.8%, p = 0.005) were independently associated with a percent decrease in the systolic LA volume index from baseline to 6-months. In conclusion, greater LA volume reduction following IASD implantation is associated with higher baseline compliance of the left atrium and higher reservoir strain of the right atrium.

Myocardial Strain in the Assessment of Patients With Heart Failure: A Review.

Importance: The cornerstones of imaging in heart failure (HF) are the measurement of systolic and diastolic function and left ventricular (LV) filling pressure. Observations: Ejection fraction and the assessment of LV filling pressure and diastolic dysfunction using the ratio of early transmitral flow and LV relaxation (E/e') are conventional imaging markers of LV function. Despite their extensive use in HF guidelines, both have significant detractions, especially in an era when HF with preserved ejection fraction is becoming the dominant presentation. In contrast, strain imaging has provided a new window into myocardial mechanics. Myocardial strain is now well validated, robust, and can easily be performed on most modern echocardiography machines. This Review summarizes the evidence in 9 situations across the stages of HF where LV global longitudinal strain and other strain parameters may provide information on risk prediction, diagnosis, assessment of treatment response, and follow-up. Conclusions and Relevance: The evolution of myocardial deformation imaging from research tool to clinical practice will provide clinicians with a useful additional imaging parameter to facilitate the assessment and risk evaluation of patients with HF.

A Prospective Pilot Study of Pocket-Carried Ultrasound Pre- and Postdischarge Inferior Vena Cava Assessment for Prediction of Heart Failure Rehospitalization.

BACKGROUND: Rehospitalization for heart failure (HF) is common, and subclinical congestion may be present at discharge. Larger inferior vena cava (IVC) size and lower collapsibility at discharge assessed via bedside ultrasound are predictive of rehospitalization; however, the utility of IVC assessment with the use of pocket-carried ultrasound (PCUS) during the transition from discharge to the posthospitalization follow-up visit (FU) has not been investigated. METHODS AND RESULTS: IVCmax and IVCmin were measured with the use of PCUS, and the collapsibility index (IVCCI = [IVCmax - IVCmin]/IVCmax) was determined. The primary outcome was 90-day rehospitalization or death. We prospectively enrolled 49 adults (71 ± 13 years of age, 51% male, 47% black, 43% preserved ejection fraction) hospitalized for HF. Nineteen patients (39%) experienced the outcome. Within the rehospitalized group, discharge and FU mean IVCmax were both >2.1 cm (2.2 ± 0.5 and 2.2 ± 0.7) and IVCCIs <50% (44 ± 20% and 45 ± 24%). Within those not rehospitalized, FU IVCmax was ≤2.1 cm (2.1 ± 0.6 and 1.9 ± 0.6; P = .038) and IVCCI >50% at both time points (55 ± 25% and 62 ± 19%; P = NS). FU IVCCI below an optimal cutoff of 42% had modest discrimination alone (c-statistic = 0.73). FU IVCCI <42% was associated with a greater hazard of the outcome independent of admission log B-type natriuretic peptide (adjusted hazard ratio = 6.8; 95% confidence interval 2.4-19.0; P < .001). CONCLUSIONS: Posthospitalization IVCCI assessment with PCUS predicts HF rehospitalization and may identify patients in need of intervention.

Relation of Sex Hormone Levels With Prevalent and 10-Year Change in Aortic Distensibility Assessed by MRI: The Multi-Ethnic Study of Atherosclerosis.

BACKGROUND: Women experience a steeper decline in aortic elasticity related to aging compared to men. We examined whether sex hormone levels were associated with ascending aortic distensibility (AAD) in the Multi-Ethnic Study of Atherosclerosis. METHODS: We studied 1,345 postmenopausal women and 1,532 men aged 45-84 years, who had serum sex hormone levels, AAD measured by phase-contrast cardiac magnetic resonance imaging, and ejection fraction>50% at baseline. Among these participants, 457 women and 548 men returned for follow-up magnetic resonance imaging 10-years later. Stratified by sex, and using mixed effects linear regression methods, we examined associations of sex hormones (as tertiles) with baseline and annual change in log-transformed AAD (mm Hg-110-3), adjusting for demographics, body size, lifestyle factors, mean arterial pressure, heart rate, hypertensive medication use (and in women, for hormone therapy use and years since menopause). RESULTS: The mean (SD) age was 65 (9) for women and 62 (10) years for men. AAD was lower in women than men (P < 0.001). In adjusted cross-sectional analysis, the highest tertile of free testosterone (compared to lowest) in women was significantly associated with lower AAD [-0.10 (-0.19, -0.01)] and the highest tertile of estradiol in men was associated with greater AAD [0.12 (0.04, 0.20)]. There were no associations of sex hormones with change in AAD over 10 years, albeit in a smaller sample size. CONCLUSIONS: Lower free testosterone in women and higher estradiol in men were associated with greater aortic distensibility at baseline, but not longitudinally. Sex hormone levels may account for differences in AAD between women and men.

A non-invasive assessment of cardiopulmonary hemodynamics with MRI in pulmonary hypertension.

PURPOSE: We propose a method for non-invasive quantification of hemodynamic changes in the pulmonary arteries resulting from pulmonary hypertension (PH). METHODS: Using a two-element Windkessel model, and input parameters derived from standard MRI evaluation of flow, cardiac function and valvular motion, we derive: pulmonary artery compliance (C), mean pulmonary artery pressure (mPAP), pulmonary vascular resistance (PVR), pulmonary capillary wedge pressure (PCWP), time-averaged intra-pulmonary pressure waveforms and pulmonary artery pressures (systolic (sPAP) and diastolic (dPAP)). MRI results were compared directly to reference standard values from right heart catheterization (RHC) obtained in a series of patients with suspected pulmonary hypertension (PH). RESULTS: In 7 patients with suspected PH undergoing RHC, MRI and echocardiography, there was no statistically significant difference (p<0.05) between parameters measured by MRI and RHC. Using standard clinical cutoffs to define PH (mPAP>25mmHg), MRI was able to correctly identify all patients as having pulmonary hypertension, and to correctly distinguish between pulmonary arterial (mPAP>25mmHg, PCWP<15mmHg) and venous hypertension (mPAP>25mmHg, PCWP>15mmHg) in 5 of 7 cases. CONCLUSIONS: We have developed a mathematical model capable of quantifying physiological parameters that reflect the severity of PH.

Four-dimensional flow assessment of pulmonary artery flow and wall shear stress in adult pulmonary arterial hypertension: results from two institutions.

PURPOSE: To compare pulmonary artery flow using Cartesian and radially sampled four-dimensional flow-sensitive (4D flow) MRI at two institutions. METHODS: Nineteen healthy subjects and 17 pulmonary arterial hypertension (PAH) subjects underwent a Cartesian 4D flow acquisition (institution 1) or a three-dimensional radial acquisition (institution 2). The diameter, peak systolic velocity (Vmax), peak flow (Qmax), stroke volume (SV), and wall shear stress (WSS) were computed in two-dimensional analysis planes at the main, right, and left pulmonary artery. Interobserver variability, interinstitutional differences, flow continuity, and the hemodynamic measurements in healthy and PAH subjects were assessed. RESULTS: Vmax, Qmax, SV, and WSS at all locations were significantly lower (P < 0.05) in PAH compared with healthy subjects. The limits of agreement were 0.16 m/s, 2.4 L/min, 10 mL, and 0.31 N/m(2) for Vmax, Qmax, SV, and WSS, respectively. Differences between Qmax and SV using Cartesian and radial sequences were not significant. Plane placement and acquisition exhibited isolated, site-based differences between Vmax and WSS. CONCLUSIONS: 4D flow MRI was used to detect differences in pulmonary artery hemodynamics for PAH subjects. Flow and WSS in healthy and PAH subject cohorts were similar between Cartesian- and radial-based 4D flow MRI acquisitions with minimal interobserver variability.

Treatment of acute heart failure in the emergency department.

Millions of patients are hospitalized for acute heart failure (AHF) every year throughout the world. Despite tremendous advances in cardiovascular care, morbidity and mortality for AHF remain high, consuming billions of health care dollars. With the aging of the population, the incidence and prevalence of HF is projected to increase. Yet, initial treatment of AHF today is similar to 40 years ago. Multiple studies have yielded new insights regarding initial management, with regards to both treatment and strategies of care. These advances will be reviewed in the context of initial or early AHF management. There remains, however, an unmet need to improve outcomes for AHF patients.

Heart failure in North America.

Heart failure is a major health problem that affects patients and healthcare systems worldwide. Within the continent of North America, differences in economic development, genetic susceptibility, cultural practices, and trends in risk factors and treatment all contribute to both inter-continental and within-continent differences in heart failure. The United States and Canada represent industrialized countries with similar culture, geography, and advanced economies and infrastructure. During the epidemiologic transition from rural to industrial in countries such as the United States and Canada, nutritional deficiencies and infectious diseases made way for degenerative diseases such as cardiovascular diseases, cancer, overweight/obesity, and diabetes. This in turn has resulted in an increase in heart failure incidence in these countries, especially as overall life expectancy increases. Mexico, on the other hand, has a less developed economy and infrastructure, and has a wide distribution in the level of urbanization as it becomes more industrialized. Mexico is under a period of epidemiologic transition and the etiology and incidence of heart failure is rapidly changing. Ethnic differences within the populations of the United States and Canada highlight the changing demographics of each country as well as potential disparities in heart failure care. Heart failure with preserved ejection fraction makes up approximately half of all hospital admissions throughout North America; however, important differences in demographics and etiology exist between countries. Similarly, acute heart failure etiology, severity, and management differ between countries in North America. The overall economic burden of heart failure continues to be large and growing worldwide, with each country managing this burden differently. Understanding the inter-and within-continental differences may help improve understanding of the heart failure epidemic, and may aid healthcare systems in delivering better heart failure prevention and treatment.

Risk assessment in pulmonary hypertension associated with heart failure and preserved ejection fraction.

BACKGROUND: Pulmonary hypertension (PH) is common in patients with left heart failure (HF), especially those with HF and preserved ejection fraction (HFpEF). However, there is limited data on risk stratification in these patients. METHODS: Baseline clinical and hemodynamic variables of 339 patients with World Health Organization (WHO) Group 2 PH, 90% of whom had HFpEF, were studied to derive a multivariate Cox proportional hazards model. A simplified prognostic risk score was created based on the outcome of all-cause mortality. Nine predictors, significant after stepwise multivariable regression (p < 0.05), were used to create the risk score. Components of the risk score were functional class, diastolic blood pressure, pulmonary artery saturation, interstitial lung disease, hypotension on initial presentation, right ventricular hypertrophy, diffusion capacity of the lung for carbon monoxide, and 2 serum creatinine variables (≤ 0.9 mg/dl and ≥ 1.4 mg/dl). RESULTS: Overall 2-year survival was 73.8% ± 2.4% in the derivation cohort, and 87.5% ± 2.3%, 66.4% ± 4.9%, and 24.4% ± 6.7% for risk scores of 0 to 2, 3 to 4, and 5+, respectively (p < 0.0001 for the trend), with a C-index of 0.76 (95% confidence interval [CI], 0.71-0.81). The risk score was validated in 2 independent PH-HFpEF cohorts: 179 patients with a C-index of 0.68 (95% CI, 0.55-0.80) and 117 patients with a C-index of 0.68 (95% CI, 0.53-0.83). For the 3 cohorts combined (N = 635), the overall C-index was 0.72 (95% CI 0.68-0.76). In all 3 cohorts individually and in the 3 cohorts combined, the risk score predicted death (hazard ratio, 1.4-1.6; p < 0.01). CONCLUSIONS: Several clinical factors independently predict death in PH-HFpEF confirmed by validation. A novel risk score composed of these factors can be used to determine prognosis and may be useful in making therapeutic decisions.