Pitfalls of mitral regurgitation assessment in the presence of mitral valve prolapse.

Adequate grading of mitral regurgitation (MR) in patients with mitral valve prolapse (MVP) in the presence of mid-late systolic jets can represent a major challenge. In this entity, jets are commonly overestimated by echocardiography. Correct quantification is crucial and highly relevant for the further management and prognosis of these oftentimes young patients. This case points out potential pitfalls and underlines the importance to systematically include qualitative, quantitative, and semi-quantitative parameters into the echocardiographic assessment.

Nitric oxide metabolites: associations with cardiovascular biomarkers and clinical parameters in patients with HFpEF.

AIMS: Heart failure with preserved ejection fraction (HFpEF) is one of the most rapidly growing cardiovascular health burden worldwide, but there is still a lack of understanding about the HFpEF pathophysiology. The nitric oxide (NO) signalling pathway has been identified as a potential key element. The aim of our study was to investigate markers of NO metabolism [l-arginine (l-Arg), homoarginine (hArg), and asymmetric and symmetric dimethylarginine (ADMA and SDMA)], additional biomarkers [N-terminal pro-B-type natriuretic peptide (NT-proBNP), endothelin-1 (ET-1), mid-regional pro-adrenomedullin (MR-proADM), copeptin, and high-sensitivity C-reactive protein (hsCRP)], and the endothelial function in an integrated approach focusing on associations with clinical characteristics in patients with HFpEF. METHODS AND RESULTS: Seventy-three patients, prospectively enrolled in the 'German HFpEF Registry', were analysed. Inclusion criteria were left ventricular ejection fraction (LVEF) ≥ 50%; New York Heart Association functional class ≥ II; elevated levels of NT-proBNP > 125 pg/mL; and at least one additional criterion for structural heart disease or diastolic dysfunction. All patients underwent transthoracic echocardiography, cardiopulmonary exercise testing, and pulse amplitude tonometry (EndoPAT™). Patients were categorized in two groups based on their retrospectively calculated HFA-PEFF score. Serum concentrations of l-Arg, hArg, ADMA, SDMA, NT-proBNP, ET-1, MR-proADM, copeptin, and hsCRP were determined. Patients had a median age of 74 years, 47% were female, and median LVEF was 57%. Fifty-two patients (71%) had an HFA-PEFF score ≥ 5 (definitive HFpEF), and 21 patients (29%) a score of 3 to 4 (risk for HFpEF). Overall biomarker concentrations were 126 ± 32 µmol/L for l-Arg, 1.67 ± 0.55 µmol/L for hArg, 0.74 (0.60;0.85) µmol/L for SDMA, and 0.61 ± 0.10 µmol/L for ADMA. The median reactive hyperaemia index (RHI) was 1.55 (1.38;1.87). SDMA correlated with NT-proBNP (r = 0.291; P = 0.013), ET-1 (r = 0.233; P = 0.047), and copeptin (r = 0.381; P = 0.001). ADMA correlated with ET-1 (r = 0.250; P = 0.033) and hsCRP (r = 0.303; P = 0.009). SDMA was associated with the left atrial volume index (ß = 0.332; P = 0.004), also after adjustment for age, sex, and comorbidities. Biomarkers were non-associated with the RHI. A principal component analysis revealed two contrary clusters of biomarkers. CONCLUSIONS: Our findings suggest an impaired NO metabolism as one possible key pathogenic determinant in at least a subgroup of patients with HFpEF. We argue for further evaluation of NO-based therapies. Upcoming studies should clarify whether subgroups of HFpEF patients can take more benefit from therapies that are targeting NO metabolism and pathway.

Left atrial function and maximal exercise capacity in heart failure with preserved and mid-range ejection fraction.

AIMS: Exercise intolerance is the leading manifestation of heart failure with preserved or mid-range ejection fraction (HFpEF or HFmrEF), and left atrial (LA) function might contribute to modulating left ventricular filling and pulmonary venous pressures. We aim to assess the association between LA function and maximal exercise capacity in patients with HFpEF or HFmrEF. METHODS AND RESULTS: Sixty-five patients, prospectively enrolled in the German HFpEF Registry, were analysed. Inclusion criteria were New York Heart Association functional class ≥ II, left ventricular ejection fraction > 40%, structural heart disease or diastolic dysfunction, and elevated levels of N terminal pro brain natriuretic peptide (NT-proBNP). LA function was evaluated through speckle-tracking echocardiography by central reading in the Charité Academic Echocardiography core lab. All patients underwent maximal cardiopulmonary exercise test and were classified according to a peak VO2 cut-off of prognostic value (14 mL/kg/min). NT-pro-BNP was measured. Twenty-nine patients (45%) reached a peak VO2  < 14 mL/kg/min (mean value 12.4 ± 1.5) and 36 patients (55%) peak VO2  ≥ 14 mL/kg/min (mean value 19.4 ± 3.9). There was no significant difference in left ventricular ejection fraction (60 ± 9 vs. 59 ± 8%), left ventricular mass (109 ± 23 vs. 112 ± 32 g/m2 ), LA volume index (45 ± 17 vs. 47 ± 22 mL/m2 ), or E/e´ (13.1 ± 4.7 vs. 13.0 ± 6.0) between these groups. In contrast, all LA strain measures were impaired in patients with lower peak VO2 (reservoir strain 14 ± 5 vs. 21 ± 9%, P = 0.002; conduit strain 9 ± 2 vs. 13 ± 4%, P = 0.001; contractile strain 7 ± 4 vs. 11 ± 6%, P = 0.02; reported lower limits of normality for LA reservoir, conduit and contractile strains: 26.1%, 12.0%, and 7.7%). In linear regression analysis, lower values of LA reservoir strain were associated with impaired peak VO2 after adjustment for age, sex, body mass index, heart rhythm (sinus/AFib), and log-NTproBNP [ß 0.29, 95% confidence interval (CI) 0.02-0.30, P = 0.02], with an odds ratio 1.22 (95% CI 1.05-1.42, P = 0.01) for peak VO2  < 14 mL/kg/min for LA reservoir strain decrease after adjustment for these five covariates. Adding left ventricular ejection fraction, it did not influence the results. On the other hand, the addition of LA strain to the adjustment parameters alone described above provided a significant increase of the predictive value for lower peak VO2 values (R2 0.50 vs. 0.45, P = 0.02). With receiver operating characteristic curve analysis, we identified LA reservoir strain < 22% to have 93% sensitivity and 49% specificity in predicting peak VO2  < 14 mL/kg/min. Using this cut-off, LA reservoir strain < 22% was associated with peak VO2  < 14 mL/kg/min in logistic regression analysis after comprehensive adjustment for age, sex, body mass index, heart rhythm, and log-NTproBNP [odds ratio 95% CI 10.4 (1.4-74), P = 0.02]. CONCLUSIONS: In this HFpEF and HFmrEF cohort, a reduction in LA reservoir strain was a sensible marker of decreased peak exercise capacity. Therefore, LA reservoir strain might be of clinical value in predicting exercise capacity in patients with HFpEF or HFmrEF.

Suppression of Tumourigenicity 2 in Heart Failure With Preserved Ejection Fraction.

Heart failure (HF), with steadily increasing incidence rates and mortality in an ageing population, represents a major challenge. Evidence suggests that more than half of all patients with a diagnosis of HF suffer from HF with preserved ejection fraction (HFpEF). Emerging novel biomarkers to improve and potentially guide the treatment of HFpEF are the subject of discussion. One of these biomarkers is suppression of tumourigenicity 2 (ST2), a member of the interleukin (IL)-1 receptor family, binding to IL-33. Its two main isoforms - soluble ST2 (sST2) and transmembrane ST2 (ST2L) - show opposite effects in cardiovascular diseases. While the ST2L/IL-33 interaction is considered as being cardioprotective, sST2 antagonises this beneficial effect by competing for binding to IL-33. Recent studies show that elevated levels of sST2 are associated with increased mortality in HF with reduced ejection fraction. Nevertheless, the significance of sST2 in HFpEF remains uncertain. This article aims to give an overview of the current evidence on sST2 in HFpEF with an emphasis on prognostic value, clinical association and interaction with HF treatment. The authors conclude that sST2 is a promising biomarker in HFpEF. However, further research is needed to fully understand underlying mechanisms and ultimately assess its full value.