Prognostic Value of Alveolar Volume in Systolic Heart Failure
The baseline characteristics of the study sample are given in Table 1. Based on clinical and spirometric data, COPD was diagnosed in 65 (25%) of 260 cases; airflow obstruction was mild in 11 patients (17%), moderate in 41 (63%), and severe in 13 (20%). In the whole sample, the median value of VA was 79% of predicted (IQR, 70 to 88%). There was a highly significant, inverse correlation of VA with NT-proBNP (r = -0.21; p < 0.001) and cardiothoracic ratio (r = -0.39; p < 0.001), and a weaker borderline significant correlation with LVEF (r = +0.11; p = 0.054).
Table 2 shows the characteristics of the study sample spit by VA category. As compared with patients having VA ≥ 80%, those with VA < 80% featured the following statistically significant differences: (a) older age; (b) higher prevalence of NYHA class III-IV, abnormal cardiothoracic ratio, persistent atrial fibrillation, COPD comorbidity, and ventilatory restriction; (c) lower FEV1 and DLCO; (d) higher levels of NT-proBNP. As regards medical treatment, significantly less patients with VA < 80% were prescribed beta-blockers and ACE-inhibitors, and significantly more were on oral anticoagulants than those with VA ≥ 80%.
Radiologic signs of interstitial lung edema were detected in 16% of the patients with VA < 80% and in 3% of those with VA ≥ 80% (p < 0.001). Similarly, small pleural effusions prevailed significantly in the lower VA category than in the other (24% vs 6%, p < 0.001), whereas no statistically significant difference was observed as regards the prevalence of radiologic signs of emphysema (11% vs 7%, p = 0.293). None of the sampled patients had evidence of overt lung fibrosis.
Follow-up was completed in all the patients, and had a median duration of 2.7 years (IQR, 1.1 to 4.2 years). The crude mortality rate was 27% (69/260) in the whole sample, 36% (49/135) in patients with VA < 80%, and 16% (20/125) in those with VA ≥ 80%. The causes of death were: heart failure (n = 44), cancer (n = 9), respiratory failure (n = 5), sudden death (n = 4), liver failure (n = 2), sepsis (n = 2), multiple trauma (n = 2), and renal failure (n = 1).
Figure 1 shows the estimated cumulative incidence of death which was significantly higher in patients with VA < 80% than in the others (p = 0.032). The mortality curves are adjusted for age, NYHA class III-IV, cardiothoracic ratio >0.5, NT-proBNP, persistent atrial fibrillation, DLCO as % predicted, and COPD comorbidity.
(Enlarge Image)
Figure 1.
Estimated cumulative mortality in the study sample split by alveolar volume (VA) as % predicted: VA<80% (red step curve); VA≥80% (blue step curve). Estimates are adjusted for age, NYHA class III-IV, cardiothoracic ratio >0.5, NT-proBNP, persistent atrial fibrillation, DLCO as % predicted, and COPD comorbidity. P-value by log-rank test = 0.032.
Table 3 describes the regression estimates of the HR of death for the two categories of VA. The unadjusted HR of death in patients with VA < 80% was 2.3-fold higher than in those with VA ≥ 80% (p = 0.002). After adjusting for potential confounders, the HR of death decreased to 1.9 but remained statistically significant (p = 0.039).
Laplace regression estimates of the percentiles of survival by VA category are displayed in Figure 2. They are adjusted for age, NYHA class III-IV, cardiothoracic ratio > 0.5, NT-proBNP, persistent atrial fibrillation, DLCO as % predicted, and COPD comorbidity. Two percent of the patients with VA < 80% died about 0.9 years earlier than those with VA ≥ 80% (p = 0.033). The difference at the 20th percentile was 0.8 years. So, the frailest were the most affected individuals by reduced VA.
(Enlarge Image)
Figure 2.
Laplace regression estimates of the 2nd and 20th percentile of survival time in the sample split by alveolar volume (VA) as % predicted (<80% vs ≥80%). Estimates are adjusted for age, NYHA class III-IV, cardiothoracic ratio >0.5, NT-proBNP, persistent atrial fibrillation, DLCO as % predicted, and COPD comorbidity.
Results
Sample
The baseline characteristics of the study sample are given in Table 1. Based on clinical and spirometric data, COPD was diagnosed in 65 (25%) of 260 cases; airflow obstruction was mild in 11 patients (17%), moderate in 41 (63%), and severe in 13 (20%). In the whole sample, the median value of VA was 79% of predicted (IQR, 70 to 88%). There was a highly significant, inverse correlation of VA with NT-proBNP (r = -0.21; p < 0.001) and cardiothoracic ratio (r = -0.39; p < 0.001), and a weaker borderline significant correlation with LVEF (r = +0.11; p = 0.054).
Table 2 shows the characteristics of the study sample spit by VA category. As compared with patients having VA ≥ 80%, those with VA < 80% featured the following statistically significant differences: (a) older age; (b) higher prevalence of NYHA class III-IV, abnormal cardiothoracic ratio, persistent atrial fibrillation, COPD comorbidity, and ventilatory restriction; (c) lower FEV1 and DLCO; (d) higher levels of NT-proBNP. As regards medical treatment, significantly less patients with VA < 80% were prescribed beta-blockers and ACE-inhibitors, and significantly more were on oral anticoagulants than those with VA ≥ 80%.
Radiologic signs of interstitial lung edema were detected in 16% of the patients with VA < 80% and in 3% of those with VA ≥ 80% (p < 0.001). Similarly, small pleural effusions prevailed significantly in the lower VA category than in the other (24% vs 6%, p < 0.001), whereas no statistically significant difference was observed as regards the prevalence of radiologic signs of emphysema (11% vs 7%, p = 0.293). None of the sampled patients had evidence of overt lung fibrosis.
Survival Analysis
Follow-up was completed in all the patients, and had a median duration of 2.7 years (IQR, 1.1 to 4.2 years). The crude mortality rate was 27% (69/260) in the whole sample, 36% (49/135) in patients with VA < 80%, and 16% (20/125) in those with VA ≥ 80%. The causes of death were: heart failure (n = 44), cancer (n = 9), respiratory failure (n = 5), sudden death (n = 4), liver failure (n = 2), sepsis (n = 2), multiple trauma (n = 2), and renal failure (n = 1).
Figure 1 shows the estimated cumulative incidence of death which was significantly higher in patients with VA < 80% than in the others (p = 0.032). The mortality curves are adjusted for age, NYHA class III-IV, cardiothoracic ratio >0.5, NT-proBNP, persistent atrial fibrillation, DLCO as % predicted, and COPD comorbidity.
(Enlarge Image)
Figure 1.
Estimated cumulative mortality in the study sample split by alveolar volume (VA) as % predicted: VA<80% (red step curve); VA≥80% (blue step curve). Estimates are adjusted for age, NYHA class III-IV, cardiothoracic ratio >0.5, NT-proBNP, persistent atrial fibrillation, DLCO as % predicted, and COPD comorbidity. P-value by log-rank test = 0.032.
Table 3 describes the regression estimates of the HR of death for the two categories of VA. The unadjusted HR of death in patients with VA < 80% was 2.3-fold higher than in those with VA ≥ 80% (p = 0.002). After adjusting for potential confounders, the HR of death decreased to 1.9 but remained statistically significant (p = 0.039).
Laplace regression estimates of the percentiles of survival by VA category are displayed in Figure 2. They are adjusted for age, NYHA class III-IV, cardiothoracic ratio > 0.5, NT-proBNP, persistent atrial fibrillation, DLCO as % predicted, and COPD comorbidity. Two percent of the patients with VA < 80% died about 0.9 years earlier than those with VA ≥ 80% (p = 0.033). The difference at the 20th percentile was 0.8 years. So, the frailest were the most affected individuals by reduced VA.
(Enlarge Image)
Figure 2.
Laplace regression estimates of the 2nd and 20th percentile of survival time in the sample split by alveolar volume (VA) as % predicted (<80% vs ≥80%). Estimates are adjusted for age, NYHA class III-IV, cardiothoracic ratio >0.5, NT-proBNP, persistent atrial fibrillation, DLCO as % predicted, and COPD comorbidity.
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