The aim of this thesis is to evaluate the role of left atrial function in clinical practice based on the following studies:
1) Determining left atrial (LA) structure and myocardial function measurements that predict pulmonary capillary wedge pressure (PCWP).
2) Identifying predictors of exercise capacity in patients with HFpEF and right ventricle (RV) dysfunction.
3) Evaluating the relationship between LA stiffness (LASt) and cardiac events in HF patients with reduced to mid-range ejection fraction.
4) Investigating the relationship between DM and LA remodelling in a group of patients with HF and reduced ejection fraction (HFrEF), and their combined impact on cardiac events.
Study I
Methods: This is a meta-analysis study. All electronic databases were searched up to December 2018 for studies on the relationship of LA diameter, LA volumes, peak atrial longitudinal strain (PALS), peak atrial contraction strain (PACS) and total emptying fraction (LAEF) with PCWP. Eighteen studies with 1343 patients were included. Summary sensitivity and specificity (with 95% CI) for evaluation of diagnostic accuracy and the best cut-off values for different LA indices in predicting raised PCWP were estimated using summary receiver operating characteristic analysis.
Results: The pooled analysis showed association between PCWP and LA diameter: Cohen’s d = 0.87, LAVI max: d = 0.92 and LAVI min: d = 1.0 (p < 0001 for all). A stronger correlation was found between PCWP and PALS: d = 1.26, and PACS: d = 1.62, total EF d = 1.22 (p < 00001 for all). PALS ≤ 19% had a summary sensitivity of 80% (65 - 90) and summary specificity of 77% (52 - 92), and diagnostic odds ratio (DOR) > 15.1, whereas LAVI ≥ 34 ml/m2 had summary sensitivity of 75% (55 - 89) and summary specificity 77% (57 - 90), and DOR > 10.1 in predicting elevated PCWP.
Conclusion: Compromised LA myocardial function and increased size predict raised cavity pressure. These results should assist in optimizing the follow-up clinical management of patients with fluctuating LA pressure.
Study II
Methods: In 143 consecutive patients with HFpEF (age 62 ± 9 years, LV EF ≥45) and 41 controls, a complete echocardiographic study was performed. In addition to conventional measurements, LA compliance was calculated using the formula: [LAV max - LAV min/LAV min × 100]. Exercise capacity was assessed using the six-minute walking test (6-MWT). Tricuspid annular plane systolic excursion (TAPSE) < 1.7 cm was used to categorize patients with RV dysfunction (n = 40) from those with maintained RV function (n = 103).
Results: Patients with RV dysfunction were older (p=0.002), had higher NYHA class (p= 0.001), higher LV mass index (p = 0.01), reduced septal and lateral MAPSE (p < 0.001 for all), enlarged LA (p = 0.001) impaired LA compliance index (p < 0.001) and exhibited a more compromised 6-MWT (p = 0.001). LA compliance index correlated more closely with 6-MWT (r = 0.51, p < 0.001) compared with the other LA indices (AP diameter, transverse diameter and volume indexed; r = -0.30, r = -0.35 and r = -0.38, respectively). In multivariate analysis, LA compliance index < 60% was 88% sensitive and 61% specific AUC = 0.80 (CI = 0.67 - 0.92; p = 0.001) in predicting exercise capacity.
Conclusion: Impaired LA compliance was profound in patients with HFpEF and RV dysfunction and seems to be the most powerful independent predictor of limited exercise capacity.
Study III
Methods: This study included 215 consecutive ambulatory heart failure (HF) patients with ejection fraction (EF) < 50% (162 HF reduced EF (HFrEF) and 53 HF mid-range EF HFmrEF)) of mean age 66 ± 11 years and 24.4% were females. Peak LA strain (PALS) was measured by speckle tracking echocardiography and E/e' recorded from the apical four-chamber view. Non-invasive left atrial stiffness (LASt) was calculated using the equation: LASt = E/e' ratio/PALS. Documented cardiac events (CE) were HF hospitalization and cardiac death.
Results: During a median follow up of 41 ± 34 months, 65 patients (30%) had CE. In multivariate analysis model, only raised LV filling pressure (E/e'), OR=2.292, (95% CI 2.099 to 2.859; p= 0.02), peak pulmonary artery pressure (PAP), OR = 1.050 (1.009 to 1.094; p= 0.01), PALS (OR = 0.932 (0.873 to 0.994; p = 0.02) and LASt OR = 3.781 (1.144 to 5.122; p = 0.001) independently predicted CE. LASt ≥ 0.76% was the most powerful predictor of CE, with 80% sensitivity, 73% specificity and AUC = 0.82, (CI = 0.73 to 0.87; p < 0.001) followed by PALS ≤ 16%, with 74% sensitivity, 72% specificity and AUC=0.77, (CI = 0.71 to 0.84; p < 0.001). These results were consistent irrespective of EF (p < 0.05).
Conclusion: In a cohort of ambulatory HFrEF and HFmrEF patients, left atrial stiffness proved the most powerful predictor of clinical outcome.
Study IV
Methods. This study included 136 consecutive HFrEF patients (65 ± 11 years), 36 had DM and 86 had increased LA stiffness (LASt). All patients underwent complete conventional and tissue Doppler echocardiographic examinations and measurements were made including LA volumes and function. LASt was calculated using the formula: LASt = E/e’ratio / LA strain.
Results. At 55 ± 37 months follow-up, free survival from CE was 69% in patients without DM and 44.4% in those with DM (p < 0.0001). The CE free-survival was lower in patients with increased LASt compared to normal LASt, (50 vs. 80%; p < 0.001), irrespective of the presence of DM (27 vs. 71%, p <0 .001). The best cut-off LASt value for predicting CE in the group as a whole was ≥ 0.82% [81% sensitivity, 72% specificity and AUC 0.82 (p < 0.001)]. LASt ≥ 0.82% also predicted CE in patients without DM [78% sensitivity, 71% specificity and AUC 0.80 (p < 0.001)] and was the strongest predictor in DM patients [85% sensitivity, 71% specificity and AUC = 0.847 (p < 0.001)].
Conclusion. High LA stiffness is associated with poor clinical outcome in patients with heart failure and reduced ejection fraction. Diabetes has an additional incremental value in determining clinical outcome in those patients.