Background Early transmitral velocity / tissue Doppler mitral annular early diastolic velocity (E/Ea) has been correlated with pulmonary capillary wedge pressure (PCWP) in a wide variety of cardiac conditions. The objective of this study was to determine the reliability of mitral E/Ea for predicting PCWP in patients admitted for advanced decompensated heart failure (ADHF). Methods and Results Prospective consecutive patients with ADHF (ejection fraction [EF] ≤30%, NYHA class III-IV symptoms) underwent simultaneous echocardiographic and hemodynamic evaluation on admission and after 48 hours of intensive medical therapy. A total of 106 patients were included (mean age 57 ±12 years, EF 24 ±8%, PCWP 21 ±7 mmHg, mitral E/Ea 20 ±12). There was a lack of correlation between mitral E/Ea and PCWP, particularly in those with larger LV volumes, more impaired cardiac indices, and the presence of cardiac resynchronization therapy. Overall, mitral E/Ea was similar among patients with PCWP > and ≤ 18 mmHg, and sensitivity and specificity for mitral E/Ea > 15 to identify a PCWP > 18 mmHg was 66% and 50%, respectively. Contrary to prior reports, we did not observe any direct association between changes in PCWP and changes in mitral E/Ea. Conclusion In decompensated patients with advanced systolic heart failure, tissue Doppler derived mitral E/Ea may not be as reliable in predicting intracardiac filling pressures, particularly in those with larger LV volumes, more impaired cardiac indices, and the presence of cardiac resynchronization therapy.

Background Trimethylamine-N-oxide (TMAO) has been linked to increased cardiovascular risk. We aim to determine the prognostic value of TMAO and its dietary precursors, choline and betaine, in heart failure (HF). Methods and Results In 112 patients with chronic systolic HF with comprehensive echocardiographic evaluation, we measured plasma TMAO, choline, and betaine by mass spectrometry. Median TMAO levels, choline, and betaine levels were 5.8 [3.6, 12.1] μM, 10.9 [8.4, 14.0] μM, 43.8 [37.1, 53.0] μM, respectively, and were correlated with each other (all p<0.0001 for both). TMAO levels were significantly higher in patients with diabetes mellitus (9.4 [4.9, 13.2] vs 4.8 [3.4, 9.8] μM, p=0.005) and in subjects with New York Heart Association (NYHA) class III or greater (7.0 [4.7, 14.8] vs 4.7 [3.4, 11.3] μM, p=0.02). Elevated TMAO, choline, and betaine levels were each associated with higher plasma NT-proBNP levels and more advanced left ventricular diastolic dysfunction, but not systolic dysfunction or inflammatory and endothelial biomarkers. Higher choline (Hazard ratio (HR) 1.64 [95% CI: 1.22 2.20], p=0.001), betaine (HR 1.51 [1.10–2.08], p=0.01), and TMAO (HR 1.48 [1.10–1.96], p=0.01) predicted increased risk for 5-year adverse clinical events (death/transplant). Only higher TMAO levels predicted incident adverse clinical events independent of age, eGFR, mitral E/septal Ea, and NT-proBNP levels (HR 1.46 [1.03 2.14], p=0.03). Conclusion Elevated plasma TMAO, choline and betaine levels are each associated with more advanced left ventricular diastolic dysfunction and portend poorer long-term adverse clinical outcomes in chronic systolic HF. However, only higher plasma TMAO levels was associated with poor prognosis after adjustment for cardio-renal indices.

Background The development of worsening renal function (WRF, defined as creatinine rise ≥0.3 mg/dL) occurs frequently in the setting of acute decompensated heart failure (ADHF) and strongly predicts adverse clinical outcomes. Neutrophil gelatinase–associated lipocalin (NGAL) is produced by the nephron in response to tubular epithelial damage and serves as an early marker for acute renal tubular injury. We sought to determine the relationship between admission serum NGAL levels and WRF in the setting of ADHF. Methods and Results We measured serum NGAL levels in 91 patients admitted to the hospital with ADHF. Patients were adjudicated by independent physician into those that did or did not develop WRF over the ensuing 5 days of in-hospital treatment. In our study cohort (68% male, mean age 61 ± 15 years, mean left ventricular ejection fraction 31 ± 14%), median admission serum NGAL level was 165 ng/mL (interquartile range [IQR] 108–235 ng/mL). Thirty-five patients (38%) developed WRF within the 5-day follow-up. Patients who developed WRF versus those without WRF had significantly higher median admission serum NGAL levels (194 [IQR 150–292] ng/mL vs. 128 [IQR 97–214] ng/mL, P = .001). High serum NGAL levels at admission were associated with greater likelihood of developing WRF (odds ratio: 1.92, 95% confidence interval 1.23–3.12, P = .004). In particular, admission NGAL ≥140 ng/mL had a 7.4-fold increase in risk of developing WRF, with a sensitivity and specificity of 86% and 54%, respectively. Conclusions The presence of elevated admission serum NGAL levels is associated with heightened risk of subsequent development of WRF in patients admitted with ADHF.

Galectin-3 plays an important role in fibroblast activation and fibrosis in animal models. Elevated galectin-3 levels are associated with poor long-term survival in heart failure (HF). We examined the relation between plasma galectin-3 levels and myocardial indices of systolic HF. We measured plasma galectin-3 in 133 chronic HF and 45 advanced decompensated HF subjects with echocardiographic and hemodynamic evaluation. In our chronic HF cohort, median plasma galectin-3 level was 13.9ng/mL [interquartile range: 12.1–16.9ng/mL]. Higher galectin-3 was associated with more advanced age (r=0.22, p=0.010) and poor renal function (estimated glomerular filtration rate [eGFR]: r= −0.24, p=0.007; cystatin C: r= 0.38, p<0.0001), and predicted all-cause mortality (Hazard ratio [HR] 1.86 [95% confidence interval: 1.36–2.54], p<0.001). In multivariate analysis, galectin-3 remained an independent predictor of all-cause mortality after adjusting for age, eGFR, left ventricular (LV) ejection fraction (EF), and mitral E/septal Ea (HR 1.94 [1.30–2.91], p=0.001). However, galectin-3 did not predict the combined endpoint of all-cause mortality, cardiac transplantation, or HF hospitalization (p>0.05). Furthermore, there were no relations between galectin-3 and LV end-diastolic volume index (r= −0.05, p=0.61), LVEF (r= 0.10, p=0.25), or LV diastolic function (mitral E/septal Ea: r= 0.06, p=0.52; left atrial volume index: r= 0.08, p=0.41). In our advanced decompensated HF cohort, we did not observe any relation between galectin-3 and echocardiographic or hemodynamic indices. In conclusion, high plasma galectin-3 levels were associated with renal insufficiency and poorer survival in patients with chronic systolic HF. However, we did not observe a relation between galectin-3 and echocardiographic or hemodynamic indices.

In chronic systolic HF, elevated plasma MPO levels are associated with an increased likelihood of more advanced HF. Moreover, elevated plasma MPO levels within a HF subject seem to be predictive of increased adverse clinical outcomes.

In patients with chronic systolic HF, RAVI is a determinant of right-sided systolic dysfunction. This quantitative and reproducible echocardiographic marker provides independent risk prediction of long-term adverse clinical events.

In chronic systolic HF, worsening LV GLS is associated with more severe LV diastolic dysfunction and RV systolic and diastolic dysfunction, and provides incremental prognostic value to LVEF.

Mitral valves in CHF are biochemically different from normal, with ECM changes that are influenced by the altered cardiac dimensions. This remodeling suggests that MR in patients with CHF may not be purely functional, and that these valves are not "normal."