Borlaug, Barry A.

Background: Diagnosis of heart failure with preserved ejection fraction (HFpEF) is challenging in euvolemic patients with dyspnea, and no evidence-based criteria are available. We sought to develop and then validate noninvasive diagnostic criteria that could be used to estimate the likelihood that HFpEF is present among patients with unexplained dyspnea to guide further testing. Methods: Consecutive patients with unexplained dyspnea referred for invasive hemodynamic exercise testing were retrospectively evaluated. Diagnosis of HFpEF (case) or noncardiac dyspnea (control) was ascertained by invasive hemodynamic exercise testing. Logistic regression was performed to evaluate the ability of clinical findings to discriminate cases from controls. A scoring system was developed and then validated in a separate test cohort. Results: The derivation cohort included 414 consecutive patients (267 cases with HFpEF and 147 controls; HFpEF prevalence, 64%). The test cohort included 100 consecutive patients (61 with HFpEF; prevalence, 61%). Obesity, atrial fibrillation, age >60 years, treatment with ≥2 antihypertensives, echocardiographic E/e’ ratio >9, and echocardiographic pulmonary artery systolic pressure >35 mm Hg were selected as the final set of predictive variables. A weighted score based on these 6 variables was used to create a composite score (H 2 FPEF score) ranging from 0 to 9. The odds of HFpEF doubled for each 1-unit score increase (odds ratio, 1.98; 95% CI, 1.74–2.30; P <0.0001), with an area under the curve of 0.841 ( P <0.0001). The H 2 FPEF score was superior to a currently used algorithm based on expert consensus (increase in area under the curve of 0.169; 95% CI, 0.120–0.217; P <0.0001). Performance in the independent test cohort was maintained (area under the curve, 0.886; P <0.0001). Conclusions: The H 2 FPEF score, which relies on simple clinical characteristics and echocardiography, enables discrimination of HFpEF from noncardiac causes of dyspnea and can assist in determination of the need for further diagnostic testing in the evaluation of patients with unexplained exertional dyspnea.

Abstract Aims Increases in left ventricular filling pressure are a fundamental haemodynamic abnormality in heart failure with preserved ejection fraction (HFpEF). However, very little is known regarding how elevated filling pressures cause pulmonary abnormalities or symptoms of dyspnoea. We sought to determine the relationships between simultaneously measured central haemodynamics, symptoms, and lung ventilatory and gas exchange abnormalities during exercise in HFpEF. Methods and results Subjects with invasively-proven HFpEF (n = 50) and non-cardiac causes of dyspnoea (controls, n = 24) underwent cardiac catheterization at rest and during exercise with simultaneous expired gas analysis. During submaximal (20 W) exercise, subjects with HFpEF displayed higher pulmonary capillary wedge pressures (PCWP) and pulmonary artery pressures, higher Borg perceived dyspnoea scores, and increased ventilatory drive and respiratory rate. At peak exercise, ventilation reserve was reduced in HFpEF compared with controls, with greater dead space ventilation (higher VD/VT). Increasing exercise PCWP was directly correlated with higher perceived dyspnoea scores, lower peak exercise capacity, greater ventilatory drive, worse New York Heart Association (NYHA) functional class, and impaired pulmonary ventilation reserve. Conclusion This study provides the first evidence linking altered exercise haemodynamics to pulmonary abnormalities and symptoms of dyspnoea in patients with HFpEF. Further study is required to identify the mechanisms by which haemodynamic derangements affect lung function and symptoms and to test novel therapies targeting exercise haemodynamics in HFpEF.

Abstract Aim Weight gain appears to accelerate age-related ventricular–arterial stiffening, which has been implicated in the development of heart failure (HF), but it is unclear whether body fat accumulation underpins this association. We evaluated the relationship of adiposity, using measures of body composition, with ventricular–arterial stiffness among the elderly in the community. Methods and results Adiposity was accessed through body mass index (BMI), waist circumference, and body fat percentage. We studied the association of these measures with carotid–femoral pulse wave velocity (cfPWV), arterial elastance index (EaI), left ventricular (LV) end-systolic elastance index (EesI) and LV end-diastolic elastance index (EedI) in 5520 community-based, elderly Atherosclerosis Risk in Communities (ARIC) Study participants, who underwent echocardiography between 2011 and 2013. BMI and waist circumference were directly associated with EaI, EedI and EesI even after adjusting for age, sex, race, hypertension, diabetes mellitus, heart rate, prevalent coronary heart disease and HF. After further adjustment for BMI, body fat percentage demonstrated significant independent linear relationships with EaI [standardized beta coefficient (β)=0.17, P&lt;0.001], EesI (β=0.08, P=0.003) and EedI (β=0.20, P&lt;0.001), and significant non-linear relationships with cfPWV (P=0.033). Conclusion In this biracial community-based cohort, increased adiposity was associated with increased ventricular–arterial stiffness among the elderly and suggests a potential mechanism by which obesity might contribute to the development of HF.

Background: Patients with combined post- and precapillary pulmonary hypertension due to left heart disease have a worse prognosis compared with isolated postcapillary. However, it remains unclear whether increased mortality in combined post- and precapillary pulmonary hypertension is simply a result of higher total right ventricular load. Pulmonary effective arterial elastance (Ea) is a measure of total right ventricular afterload, reflecting both resistive and pulsatile components. We aimed to test whether pulmonary Ea discriminates survivors from nonsurvivors in patients with pulmonary hypertension due to left heart disease and if it does so better than other hemodynamic parameters associated with combined post- and precapillary pulmonary hypertension. Methods and Results: We combined 3 large heart failure patient cohorts (n=1036) from academic hospitals, including patients with pulmonary hypertension due to heart failure with preserved ejection fraction (n=232), reduced ejection fraction (n=335), and a mixed population (n=469). In unadjusted and 2 adjusted models, pulmonary Ea more robustly predicted mortality than pulmonary vascular resistance and the transpulmonary gradient. Along with pulmonary arterial compliance, pulmonary Ea remained predictive of survival in patients with normal pulmonary vascular resistance. The diastolic pulmonary gradient did not predict mortality. In addition, in a subset of patients with echocardiographic data, Ea and pulmonary arterial compliance were better discriminators of right ventricular dysfunction than the other parameters. Conclusions: Pulmonary Ea and pulmonary arterial compliance more consistently predicted mortality than pulmonary vascular resistance or transpulmonary gradient across a spectrum of left heart disease with pulmonary hypertension, including patients with heart failure with preserved ejection fraction, heart failure with reduced ejection fraction, and pulmonary hypertension with a normal pulmonary vascular resistance.

Background— In severe asymptomatic primary mitral valve regurgitation without risk factors, surgery strategy is controversial. We sought to clarify whether being symptomatic corresponds to the hemodynamic burden and reduced exercise capacity. A better understanding of this may contribute to optimize timing of surgery. Methods and Results— Subjects with asymptomatic (New York Heart Association functional class I, n=29) or symptomatic (New York Heart Association functional class II and III, n=28) significant primary mitral valve regurgitation (effective regurgitant orifice, ≥0.30 cm 2 ; left ventricular ejection fraction, >60%) were included. Right heart catheterization during rest and exercise, echocardiography, magnetic resonance imaging, and peak oxygen consumption test was performed. Symptomatic subjects had significantly higher pulmonary capillary wedge pressure at rest (14±4 versus 11±3 mm Hg; P =0.003) and at maximal exercise (30±6 versus 25±7 mm Hg; P =0.02) and higher mean pulmonary artery pressure (PAP) at rest (22±7 versus 18±4 mm Hg; P =0.005) and maximal exercise (46±8 versus 39±7 mm Hg; P =0.005) than asymptomatic subjects. Among asymptomatic subjects with normal resting value, exercise testing revealed a systolic PAP >60 mm Hg in 34%. Also the reverse response with minimal increase in pulmonary capillary wedge pressure and mean PAP during exercise was seen, especially in asymptomatic subjects. Among symptomatic subjects, we found a significant inverse correlation between resting mean PAP and left ventricular ejection fraction ( r =−0.52; P =0.02) and right ventricular ejection fraction ( r =−0.67; P <0.01). Peak oxygen consumption was equal and normal in both groups and correlated with left ventricular stroke volume but not with pulmonary capillary wedge pressure. Conclusions— Symptoms in patients with severe mitral valve regurgitation relate to congestion (pulmonary capillary wedge pressure and PAP), but not to peak oxygen consumption, which is determined by forward left ventricular stroke volume. Exercise testing reveals a higher mitral valve regurgitation burden in apparently asymptomatic patients. Clinical Trial Registration— URL: http://www.clinicaltrials.gov . Unique identifier: NCT02961647.