Our findings indicated that concentric hypertrophy was predominant in patients on chronic HD, and that the concentric LVH group had increased risks of cardiovascular and all-cause mortality. Moreover, patients with severe concentric LVH were at the highest risk of cardiovascular mortality, followed by mild-to-moderate concentric LVH, severe eccentric LVH, and mild-to-moderate eccentric LVH; a similar trend was observed for all-cause mortality.
Many patients with concentric LVH in our study had hypertension, DM, or both. Studies have demonstrated that concentric hypertrophy is the most common geometric pattern in the hypertensive group and DM population. The Resist-POL study, comprising 155 patients with resistant hypertension, revealed a high prevalence of concentric LVH (33%), followed by concentric remodeling (25.8%), normal geometry (24.4%), and eccentric hypertrophy (16.8%) [18]. Another study also found that the prevalence of concentric hypertrophy was higher than that of eccentric patterns in untreated hypertensive patients [19]. Nardi et al. confirmed that in patients with hypertension and chronic kidney disease, concomitant diabetes is associated with increased LV wall thickness and higher concentric geometry [20]. Both hypertension and DM are vital factors contributing to concentric LVH. Eguchi et al. noted stronger associations between higher wall thickness and higher prevalence of concentric LVH in patients with type 2 diabetes than in those without diabetes [21]. The development of LVH in DM occurs through multiple potential mechanisms, including hyperglycemia-associated cellular alterations, oxidative stress, inflammation, insulin resistance, AMP-activated kinase (AMPK), and mammalian target of rapamycin (mTOR) signaling [22]. In particular, cardiac steatosis, decreased myocardial energetics, and systolic dysfunction are potential mechanisms underlying concentric LV remodeling in the diabetes population [23].
Consistent with our findings, a study conducted in China involving 131 people also observed that concentric LVH (n = 71) was more prevalent than eccentric LVH (n = 9) [8]. By contrast, the CONvective TRAnsport Study (CONTRAST) reported that concentric patterns were mainly observed in patients with chronic kidney disease not undergoing HD, whereas eccentric hypertrophy was predominant in patients on HD [10, 24]. The inconsistency between our investigation and the CONTRAST may be related to the high percentage of patients with hypertension (82.3%) and DM (48.9%) in our study compared with only 26.8% of patients with LVH diagnosed as having DM in the previous study [24]. Given that our finding is consistent with those of the Chinese study, but not with those of the Western study, the influence of ethnicity cannot be neglected. Future large-scale studies are warranted to determine the potential explanations underlying these findings.
Notably, compared with eccentric LVH, concentric hypertrophy has an adverse prognosis in terms of cardiovascular mortality and all-cause mortality. Koren et al. investigated patients with essential hypertension and reported that those with concentric hypertrophy had the highest risks of cardiovascular events and death, whereas those with normal geometry had the lowest risks [25]. In a prospective study, Muiesan et al. found that the persistence or development of concentric LVH was the strongest predictor of cardiovascular events in the hypertensive population [26]. The close relationship between concentric geometry and cardiovascular events might be explained by impaired myocardial contractility, severe diastolic filling abnormalities, increased oxygen consumption, a higher risk of arrhythmias, and sudden death. Only a few studies have investigated the association between left ventricular geometry and adverse events in the HD population. In the CONTRAST, a higher risk of sudden death (adjusted HR: 5.22; 95% CI: 1.14–23.94, p = 0.03) was noted in the eccentric LVH group than in the concentric LVH group; however, the incidence of all-cause mortality or cardiovascular death (adjusted HRs: 0.87 and 1.49; p values: 0.57 and 0.36, respectively) was not significantly different between the two groups [10]. The inconsistent results might be attributed to several reasons. First, Zuijdewijn et al. [10] only distinguished patients by geometric patterns and not LVH severity, the inconsistencies in the LVH severity division between different geometries might cause nonsignificant results for all-cause mortality and cardiovascular death. Second, we could not determine the patients’ fluid status; stable volume control may explain the lower risks of cardiovascular mortality and all-cause mortality in patients with the eccentric pattern. Furthermore, the shorter dialysis vintage in the eccentric LVH group may also influence the prognosis.
In patients with end-stage kidney disease, LVH progresses with dialysis vintage [27]. Zoccali et al. enrolled 161 patients on regular dialysis without a history of congestive heart failure for 18 months and shown that LVMI increased by 7% at the end of the study [28]. Oguz et al. followed up 80 patients on HD and found that LVMI was positively correlated with dialysis vintage (r = 0.387, p = 0.005) [29]. Only 32.5% of patients had mild-to-moderate (concentric or eccentric) LVH in our study, which might be related to longer dialysis vintage. Moreover, several studies have demonstrated a strong relationship between increasing LVMI and poor clinical outcomes. In a study of 40,138 adults by Bouzas-Mosquera et al., patients with severe increase in left ventricular mass had the highest 10-year mortality (46.4%), followed by those with moderately increased left ventricular mass (37.4%), mild increase in left ventricular mass (31.9%), and normal left ventricular mass (26.8%, p < 0.001) [14]. However, the risk of clinical end points was decreased by the reduction in LVMI. A prospective cohort substudy including 941 patients aged 55–80 years with essential hypertension and LVH from the Losartan Intervention for Endpoint Reduction in Hypertension (LIFE) trial had LV mass measured by echocardiography. At the 4.8-year follow-up, lower in-treatment LVMI decreased cardiovascular mortality by 38% and all-cause mortality by 28% [30].
To the best of our knowledge, ours is the first study exploring the association of LVH geometric patterns and severity with clinical outcomes, including cardiovascular mortality, all-cause mortality, and MACEs in patients on chronic HD. As mentioned earlier in the text, increasing LVMI was strongly related to a higher risk of cardiovascular events, and concentric patterns had worse outcomes than eccentric patterns. This may explain why the severe concentric LVH group had the poorest prognosis among the four groups.
This study has some limitations. First, this study was a single-center, retrospective, and nonrandomized study, which may have inherent shortcomings such as selection bias and unaccounted confounders. Second, our sample size was small. Third, although all the examinations were performed by professional cardiologists, echocardiography is a highly operator-dependent technique, and we could not exclude operating differences. Fourth, the follow-up time of echocardiography varies, which might be pre- or post-dialysis, and may affect the fluid status in our patients. Finally, other factors that may affect the outcomes, such as the severity of comorbidities, quality of life, and patient compliance, were not evaluated because of incomplete information.