Corresponding Author
Key Words: hemodynamic phenotypes, LV recovery, peripartum cardiomyopathy
Peripartum cardiomyopathy (PPCM) is a de novo, potentially reversible cardiomyopathy that occurs near the end of pregnancy or in the months following delivery.1 Risk factors for the development of PPCM include factors such as age, race and ethnicity, multiparity, multiple gestation, and preeclampsia.2 Recovery rates have varied in different studies and are lower in African Americans, patients with delayed presentation, and those with severe left ventricular (LV) dysfunction or larger LV diameters.2, 3, 4 In contrast, preeclampsia is associated with better recovery.3 Despite improved knowledge about PPCM over the past decade, gaps persist in our understanding of LV recovery.
In this issue of JACC: Asia, Meledin et al5 address this gap in their study of 89 women with PPCM in Israel (78%) and Indonesia (22%). All women were diagnosed with PPCM postdelivery, with 28% having a late diagnosis. Most patients (>90%) received guideline-directed medical therapy for heart failure, but only 9% received bromocriptine. In total, 70% of the patients had LV recovery (left ventricular ejection fraction [LVEF] >50%). In the multivariable analysis, LVEF >35% and LV end-diastolic diameter ≤55 mm were predictors of LV recovery with an area under the curve of 0.847. These findings are aligned with previous studies showing that LV size and systolic function predict LV recovery in PPCM.4
What is unique about the study is the advanced echocardiography-based hemodynamic assessment in a subset of 43 patients. Patients in the nonrecovery group had more LV dilatation, a more pronounced sphericity index, lower forward stroke volume, and lower forward cardiac output (CO) compared to the recovery group. However, total stroke volume and total CO were slightly higher in the nonrecovery group, possibly caused by a larger proportion of patients with mitral regurgitation. Although patients in the recovery group had higher LVEF and greater effective arterial elastance, there were no differences in the global longitudinal strain or myocardial work index. There was also no difference in the MAP; however, the estimated systemic vascular resistance was increased and the total arterial compliance was lower in the nonrecovery group compared with the recovery group. Women in the nonrecovery group also had less myocardial fiber stiffness compared with women in the recovery group. Thus, in addition to the well-known association between poor LV recovery with LV dimensions and LVEF, this study shows that other markers of LV remodeling (ie, more sphericity), ventriculo-arterial coupling, myocardial stiffness, and systemic vascular resistance differ in patients with and without LV recovery.
The authors then used cluster analysis in the subset of patients with advanced noninvasive hemodynamics to identify 3 unique PPCM phenotypes (clusters).
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1.
Cluster 1 (n = 8) had the lowest rates of LV recovery (12.5%). This group was predominantly from Israel (88%), had more delayed presentation, had no gestational hypertension/preeclampsia, and 50% had significant mitral regurgitation. This cluster had decreased forward cardiac output, LVEF, global longitudinal strain, and contractility index (load-dependent), and had low end-diastolic elastance (load-independent), suggesting severe contractility impairment and markedly remodeled ventricles. The authors propose that patients in this cluster have an unfavorable energetic efficiency state with poor ventriculo-arterial coupling and increased wasted work, which may contribute to adverse remodeling and less recovery of LV systolic function. However, other underlying mechanisms that could also influence recovery rate, such as genetic predisposition, were not studied. Furthermore, given the late diagnosis in this cluster, it is possible that these patients sustained LV insult for a longer time without appropriate treatment, potentially leading to more myocardial damage.
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2.
Cluster 2 (n = 14) had a higher recovery rate (78.6%), were predominantly from Indonesia (86%), and had a high rates of gestational hypertension/preeclampsia (79%). This cluster had low CO with higher mean arterial blood pressure and effective arterial elastance when compared with the other clusters. The patients had severely reduced LVEF and GLS (load-dependent) but preserved end-systolic elastance (load independent), suggesting preserved contractility. Ventriculo-arterial coupling and myocardial fiber stress were also preserved. The authors suggest that patients in this cluster had preserved intrinsic contractility based on load-independent indexes. This group of patients also had a shorter time to diagnosis, likely caused by the coexistence of hypertensive disorders of pregnancy, leading to an early diagnosis and treatment when compared with normotensive individuals. The clinical characteristics and recovery rate in this cluster are consistent with previous studies, which have shown that women with PPCM and hypertensive disorders of pregnancy have a greater likelihood of recovery.6,7 The authors hypothesize that the hemodynamic profile in this cluster may be influenced by vascular mediators and unbalanced antiangiogenic factors, such as sFLT1, similar to that seen in women with preeclampsia in general.8 High levels of sFLT1 are seen in women with PPCM, although the coexistence with preeclampsia and its impact on sFLT1 values were not specified.9
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3.
Cluster 3 (n = 18) had the best recovery rate (100%). This group was predominantly from Israel (66%), 50% had gestational hypertension/preeclampsia, and only 1 patient had significant mitral regurgitation. The group had moderately reduced LVEF with minimal remodeling and preserved cardiac output. This cluster seemed to have a milder form of the disease. However, the time to diagnosis was significantly shorter when compared with patients in other clusters which could have had an important impact on outcomes.
The authors hypothesize that PPCM could be stratified into a cardio-depressive subtype, similar to cluster 1, or related to vascular hemodynamics, such as in cluster 2. However, there are several limitations to the study. First, the overall numbers are small, and the subgroups in the cluster analysis were even smaller. Although hypothesis-generating, larger studies are needed to understand PPCM subtypes. In addition, race and ethnicity are associated with the development of PPCM and LV recovery.3 However, only women from 2 countries were included in this study, which limits the generalizability of the findings, particularly considering African Americans, Haitians, and Nigerians are at the highest risk for PPCM. Preeclampsia has a unique pathobiology, and lack of distinction between preeclampsia and gestational hypertension may have also impacted results. Cardiac medications can affect both noninvasive hemodynamic measures and LV recovery but this was not examined in this study. Finally, this was a retrospective study, and some echocardiographic parameters such as left atrial dimensions or right ventricular size and function were not included. Furthermore, contemporary measures of echocardiographic variables, such as 3-dimensional analysis of LV volumes and LVEF, or cardiac magnetic resonance assessment of myocardial fibrosis, might further improve our understanding of LV recovery.
Despite the limitations, we congratulate the authors for this intriguing study addressing the variability in LV recovery in patients with PPCM. By identifying different clinical and hemodynamic subtypes, there is the potential for tailoring risk stratification and medical treatment and improving outcomes in this young patient cohort.
Funding support and author disclosures
The authors have reported that they have no relationships relevant to the contents of this paper to disclose.
Footnotes
The authors attest they are in compliance with human studies committees and animal welfare regulations of the authors’ institutions and Food and Drug Administration guidelines, including patient consent where appropriate. For more information, visit the Author Center.
References
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