Background
Peripartum cardiomyopathy (PPCM) is a rare, life-threatening pregnancy-associated disease that is typically marked by ventricular dysfunction. The incidence of PPCM is gradually increasing [
1] and varies geographically, most likely due to socioeconomic and genetic factors [
2]. Previous studies have reported the incidence rates of the disease in different geographical regions as follows: 1 per 300 live births in Haiti [
3], 1 per 346 live births in China [
4], 1 per 1000 live births in South Africa [
5], and 1 per 900–4000 live births in the United States [
6‐
8]. Although viral myocarditis, abnormal immune responses to pregnancy, abnormal responses to hemodynamic stress during pregnancy, cytokine-induced inflammation, and genetic factors have been suggested to be involved in the pathogenesis of PPCM, the precise pathogenetic mechanism remains unclear [
9]. The reported outcomes vary from recovery of the left ventricular (LV) ejection fraction (LVEF) within 6 months of diagnosis in 73% of the study patients [
10] to the need for heart transplantation or even death [
11,
12]. The lack of prognostic indicators in PPCM patients is another important clinical challenge [
13].
Cardiovascular magnetic resonance imaging (CMR) is a recognized radiation-free technique for assessing cardiac structure and function and myocardial tissue characterization. Several case series and reports have shown that CMR late gadolinium enhancement (LGE) has potential value in predicting poor clinical outcomes in PPCM patients [
11,
14,
15]. However, two recent multicenter and nationwide studies showed that LGE at the baseline and during follow-up were uncommon (only 3.6–14%) in PPCM [
16,
17]. Furthermore, patients who did not have LGE also showed poor clinical outcomes [
18]. This suggests that LGE alone has limitations as a prognostic indicator in PPCM patients. Furthermore, two case series showed myocardial edema by using T2-weighted images in PPCM patients [
18,
19], while another case series showed no obvious edema on T2-weighted images [
14]. This may be due to the inherent limitations of T2-weighted imaging or poor image quality [
20]. CMR with native T1 and T2 mapping offers a unique noninvasive way to quantify myocardial diffused fibrosis, measure extracellular volume (ECV), and detect myocardial edema. A recent CMR study with T1 mapping showed that LV remodeling is associated with myocardial hypertrophy, but not with edema or diffuse fibrosis of the myocardium or LV contractile dysfunction during normal pregnancy [
21]. However, no study has analyzed myocardial tissue characterization in PPCM by native T1 and T2 mapping or its predictive value for outcomes in PPCM patients. Therefore, the objective of our study was to analyze myocardial tissue characterization on CMR with native T1 and T2 mapping techniques and determine their potential value for predicting LV function recovery.
Intra- and inter-observer reproducibility
Both intra-observer and inter-observer reproducibility for assessments of ECV (intra: intraclass correlation [ICC], 0.96 [0.90 to 0.98]; coefficient of variation [COV], 3.01%; inter: ICC, 0.96 [0.90 to 0.98]; COV, 3.20%), native T1 (intra: ICC, 0.96 [0.90 to 0.98]; COV, 1.15%; inter: ICC, 0.94 (0.86 to 0.98); COV, 1.87%), and T2 (intra: ICC, 0.99 [0.97 to 0.99]; COV, 1.20%; inter: ICC, 0.97 [0.93 to 0.99]; COV, 1.63%) were excellent.
Discussion
To the best of our knowledge, this is the first study reporting quantitative T1 and T2 mapping in PPCM patients. Our findings suggest that CMR native T1 and T2 mapping may be imaging markers with prognostic potential in PPCM. ECV shows an independent association with LV function recovery in PPCM patients.
In our cohort, none of the 21 PPCM patients had hypertension or preeclampsia. Prior studies have reported that hypertension and preeclampsia are risk factors for PPCM [
10,
25]. However, a recent review of PPCM indicated that preeclampsia or pregnancy-induced hypertension could also trigger pulmonary edema in the absence of PPCM [
1]. Furthermore, one recent study directly compared PPCM with hypertension-associated heart failure in pregnancy (HHFP): the results showed that HHFP was associated with different clinical characteristics (cardiac hypertrophy, a preserved EF, and a better prognosis), indicating that the presence of hypertension in pregnancy-associated HF may not indicate PPCM [
26]. We are uncertain why none of the patients in our study had hypertension, unless it is related to racial differences [
10], the small sample size, or other unknown reasons, although all 21 cases met all of the diagnostic criteria for PPCM.
Unlike previous studies in which the initial LVEF was reported to be a good predictor of LVEF recovery [
10,
27,
28], we did not find that the LVEF-recovered group had significantly higher initial LVEFs than those in the unrecovered group. Previous studies have shown that PPCM is associated with higher rates of thromboembolism than other forms of cardiomyopathy [
29,
30]. In addition, many studies have shown that a ventricular thrombus in a PPCM patient is an indicator of poor recovery of LV function [
31,
32]. One of the two patients with LV thrombi in our study had unrecovered LV function. Although another patient eventually showed LV recovery, she was readmitted due to signs and symptoms of HF.
In the few previously published CMR studies of PPCM with limited sample sizes, the presence of LGE was likely to predict poor clinical outcomes [
14,
15,
19], while our study showed that eight of the 21 PPCM patients had LGE and the unrecovered group had a higher percentage of LGE. However, a recent multicenter study of 34 PPCM patients did not demonstrate the value of focal non-ischemic LGE, which occurred in 71% of the study population [
33]. In contrast, another multicenter cohort study reported a very low prevalence of LGE (only 5%) among 40 PPCM patients [
16]. Compared to LGE, the T1 mapping technique may show better performance in quantifying the degree of extracellular matrix or interstitial expansion, particularly in pathologies where the differences between normal and affected myocardium are less obvious [
34]. Native T1 can be obtained without the use of gadolinium-based contrast, while ECV can detect early fibrosis changes not always detectable by LGE [
35]. Previous studies have shown that native T1 and ECV have good predictive value in dilated cardiomyopathy [
34,
36], perhaps better than LGE quantification or mid-wall LGE [
37]. Both native T1 and ECV correlated well with the histological collagen volume, which may provide reproducible information on diffuse fibrosis [
38]. PPCM and idiopathic dilated cardiomyopathy share some genetic [
39] and clinical characteristics, and thus, T1 mapping might be adopted in a similar scenario. We evaluated ECV in PPCM, and the unrecovered group showed a significantly higher value. Moreover, ECV showed an independent association with the LV recovery in PPCM. In addition, Kaplan-Meier analysis revealed that patients with a higher ECV were at a higher risk of MACEs. A recent CMR study with T1 mapping showed that during normal pregnancy, there is no elevated native T1 [
21]. In our study, LV native T1 was obviously higher than that in normal controls, which indicated that the myocardial characteristics had changed in PPCM. Regarding the subgroup analysis of the 10 PPCM patients who underwent follow-up CMR imaging, a significant decrease was noted in the dynamic change in native T1 at followup. This may indicate an improvement in the myocardial tissue characteristics of PPCM patients. However, due to the small sample size, only a trend rather than statistical significance was observed between LV-recovered and unrecovered groups among those who underwent serial CMR imaging. Further studies on the dynamic changes in myocardial tissue characteristics with a larger sample size are needed.
PPCM is considered to be a form of cardiomyopathy accompanied by inflammation and oxidative stress [
40‐
42]. One case series of CMR findings in PPCM showed that myocardial inflammation in the acute stage was demonstrated by the T2 ratio [
18], whereas another case series showed no elevation of the T2 ratio in the acute stage, with only 1 of 10 follow-up images showing an elevated T2 ratio [
14]. We also found T2 evaluations according to T2 mapping were significantly higher, indicating the presence of edema, in the PPCM group than in the control group. Due to the inherent limitations of the T2 weighted-image method, T2 mapping is preferred to identify edema of the myocardium [
20]. Meanwhile, we found that the LVEF-unrecovered group had a higher T2 than the recovered group. This indicates that the degree of inflammation may be associated with PPCM prognosis.
Previous studies have suggested that gamma globulin has a therapeutic effect on the improvement of LVEF in PPCM patients [
42]; however, the exact efficacy of gamma globulin remains controversial [
43]. In the present study, we treated PPCM patients with the guideline-directed medical therapy for HF patients, which includes ACEI/ARB, β-blockers, aldosterone, diuretics, and warfarin. Since immunoglobulins were not included in the current study, we could not evaluate their efficacy. In addition, we believe that an early risk assessment of whether a PPCM patient might relapse or not mainly helps doctors identify patients who need more long-term follow-up and greater clinical attention. Hence, predictors of CMR imaging are of great significance for clinical decision-making and communicating with PPCM patients and their families.
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