IMPORTANCEDiagnosis of heart failure with preserved ejection fraction (HFpEF) among dyspneic patients without overt congestion is challenging. Multiple diagnostic approaches have been proposed but are not well validated against the independent gold standard for HFpEF diagnosis of an elevated pulmonary capillary wedge pressure (PCWP) during exercise. OBJECTIVE To evaluate H 2 FPEF and HFA-PEFF scores and a PCWP/cardiac output (CO) slope of more than 2 mm Hg/L/min to diagnose HFpEF. DESIGN, SETTING, AND PARTICIPANTS This retrospective case-control study included patients with unexplained dyspnea from 6 centers in the US, the Netherlands, Denmark, and Australia from March 2016 to October 2020. Diagnosis of HFpEF (cases) was definitively ascertained by the presence of elevated PCWP during exertion; control individuals were those with normal rest and exercise hemodynamics. MAIN OUTCOMES AND MEASURES Logistic regression was used to evaluate the accuracy of HFA-PEFF and H 2 FPEF scores to discriminate patients with HFpEF from controls. RESULTS Among 736 patients, 563 (76%) were diagnosed with HFpEF (mean [SD] age, 69 [11] years; 334 [59%] female) and 173 (24%) represented controls (mean [SD] age, 60 [15] years; 109 [63%] female). H 2 FPEF and HFA-PEFF scores discriminated patients with HFpEF from controls, but the H 2 FPEF score had greater area under the curve (0.845; 95% CI, 0.810-0.875) compared with the HFA-PEFF score (0.710; 95% CI, 0.659-0.756) (difference, −0.134; 95% CI, -0.177 to −0.094; P < .001). Specificity was robust for both scores, but sensitivity was poorer for HFA-PEFF, with a false-negative rate of 55% for low-probability scores compared with 25% using the H 2 FPEF score. Use of the PCWP/CO slope to redefine HFpEF rather than exercise PCWP reclassified 20% (117 of 583) of patients, but patients reclassified from HFpEF to control by this metric had clinical, echocardiographic, and hemodynamic features typical of HFpEF, including elevated resting PCWP in 66% (46 of 70) of reclassified patients. CONCLUSIONS AND RELEVANCEIn this case-control study, despite requiring fewer data, the H 2 FPEF score had superior diagnostic performance compared with the HFA-PEFF score and PCWP/CO slope in the evaluation of unexplained dyspnea and HFpEF in the outpatient setting.

Background: Because of limited accuracy of noninvasive tests, diastolic stress testing plays an important role in the diagnostic work-up of patients with heart failure with preserved ejection fraction (HFpEF). Exercise right heart catheterization is considered the gold standard and indicated when HFpEF is suspected but left ventricular filling pressures at rest are normal. However, performing exercise during right heart catheterization is not universally available. Here, we examined whether pulmonary capillary wedge pressure (PCWP) during a passive leg raise (PLR) could be used as simple and accurate method to diagnose or rule out occult-HFpEF. Methods: In our tertiary center for pulmonary hypertension and HFpEF, all patients who received a diagnostic right heart catheterization with PCWP-measurements at rest, PLR, and exercise were evaluated (2014–2020). The diagnostic value of PCWP PLR was compared with the gold standard (PCWP EXERCISE ). Cut-offs derived from our cohort were subsequently validated in an external cohort (N=74). Results: Thirty-nine non-HFpEF, 33 occult-HFpEF, and 37 manifest-HFpEF patients were included (N=109). In patients with normal PCWP REST (<15 mmHg), PCWP PLR significantly improved diagnostic accuracy compared with PCWP REST (AUC=0.82 versus 0.69, P =0.03). PCWP PLR ≥19 mmHg (24% of cases) had a specificity of 100% for diagnosing occult-HFpEF, irrespective of diuretic use. PCWP PLR ≥11 mmHg had a 100% sensitivity and negative predictive value for diagnosing occult-HFpEF. Both cut-offs retained a 100% specificity and 100% sensitivity in the external cohort. Absolute change in PCWP PLR or V-wave derived parameters had no incremental value in diagnosing occult-HFpEF. Conclusions: PCWP PLR is a simple and powerful tool that can help to diagnose or rule out occult-HFpEF.

Background Echocardiography is considered the cornerstone of the diagnostic workup of heart failure with preserved ejection fraction. Thus far, validation of the 2016 American Society of Echocardiography/European Association of Cardiovascular Imaging (ASE/EACVI) echo‐algorithm for evaluation of diastolic (dys)function in a patient suspected of heart failure with preserved ejection fraction has been limited. Methods and Results The diagnostic performance of the 2016 ASE/EACVI algorithm was assessed in 204 patients evaluated for unexplained dyspnea or pulmonary hypertension with echocardiogram and right heart catheterization. Invasively measured pulmonary capillary wedge pressure (PCWP) was used as the gold standard. In addition, the diagnostic performance of H 2 FPEF score and NT‐proBNP (N‐terminal pro‐B‐type natriuretic peptide) were evaluated. There was a poor correlation between indexed left atrial volume, E/e′ (septal and average) or early mitral inflow (E), and PCWP ( r =0.25–0.30, P values all <0.01). No correlation was found in our cohort between e′ (septal or lateral) or tricuspid valve regurgitation and PCWP. The correlation between diastolic function grades of the ASE/EACVI algorithm and PCWP was poor ( r =0.17, P <0.05). The ASE/EACVI algorithm had a sensitivity and specificity of 35% and 87%, respectively; an accuracy of 67% and an area under the curve of 0.56. Moreover, in 30% of cases the algorithm was not applicable or indeterminate. H 2 FPEF score had a modest correlation with PCWP ( r =0.44, P <0.0001), and accuracy was 73%; NT‐proBNP correlated weakly with PCWP ( r =0.24, P <0.001), and accuracy was 57%. Conclusions The 2016 ASE/EACVI algorithm for the assessment of diastolic function has a limited diagnostic accuracy in patients evaluated for unexplained dyspnea and/or pulmonary hypertension, and especially sensitivity to detect diastolic dysfunction was low.