DISCUSSION:
PPCM is a rare cause of HF, and incidence changes according to region
and ethnicity. PPCM diagnosis is made by exclusion of the other causes
of cardiomyopathies. The etiology of PPCM is uncertain; predisposition
and acquired factors may take part. (1) This retrospective designed
study evaluated clinical, echocardiographic, and cardiac magnetic
resonance imaging, survival and recovery characteristics.
In the US, population incidence ranges from 1 in 100 to 1 in 4000, this
rate was highest in Nigeria with 1/100 patients, and 1/400 in Haiti
reports. (3) In our HF cohort, the incidence rate was 1.6/100 patients.
This incidence rate was high as compared to the literature. The higher
incidence rate in our institute could be the tertiary and referral
center for HF patients. 57.9% of patients were referred to our center
assessment for resolved acute HF. Ethnicity was impressed in the studies
that African-American women were more predisposed to PPCM. IPAC registry
results showed that African-American women had low initial LVEF, worse
prognosis, and lower recovery rate than white women (4). In our study,
all patients’ ethnicity was caucasian white women; therefore, no
comparison could be made regarding ethnicity.
Hypertension was present in six (16.2%) patients before pregnancy, and
preeclampsia was developed in 4 (10.8%) patients before presentation
with HF. Preeclampsia-developed patients did not reveal any differences
regarding the primary end-points. However, in four patients, LVEF
recovered during the follow-up course (p=0.016). This finding could be
ascertained by abruptly increased afterload may have caused left
ventricular dysfunction with a predisposition to HF and
pregnancy-related hormonal or molecular imbalance that shares a similar
mechanism. (1) Clinical and cardiac imaging findings did not relate
significantly to primary end-points.
Haghikia et al. analyzed 115 patients in the German registry. 19
(16.5%) patients reported a positive family history of cardiomyopathy.
Family history was accepted as positive when PPCM, DCM, sudden death,
and arrhythmias in family first-degree relatives were present. The
recovery rate was not influenced by family history. (5) In our study,
four patients had a family history of non-ischemic HF; this finding did
not affect the primary end-point or LVEF recovery. Genetic analyses
could not be performed on these patients.
PPCM has been associated with higher LVEF recovery rates, primarily seen
in the first six months. The IPAC registry analyzed outcomes and
predictors of recovery in 100 patients. The enrolled patient’s diagnosis
was consistent with idiopathic non-ischemic cardiomyopathy. In the early
postpartum period, mean LVEF increased from 0.35 (0.09 to 0.55) in
twelve months. For women enrolled later in the course of the disease,
LVEF stayed the same for 12 months, but it was lower than early
postpartum women. Follow-up LVEF differed by race at 6 and 12 months.
(4)
ESC EORP PPCM registry 2020, 730 patients were assessed. Results showed
that recovery (LVEF>%50) occurred in 46% of the women,
and 23% of women’s left ventricular dysfunction persisted at six
months. (6)
In our cohort, left ventricular systolic function recovery was accepted
as an improvement by 10% and increasing over 40%. Thirteen (35.1%)
patients’ left ventricle systolic function recovered during the
follow-up. The median time to recovery was 281.5 (IQR [78.7-358])
days. In patients admitted to our hospital early in the course of the
disease recovery rate was 46.7%, and in referred patients, the recovery
rate was 27.3% (p=0.30).
In PPCM, known for reversibility of the left ventricular systolic
function, mortality is less announced in the studies. In the IPAC
registry, follow-up at one-year mortality ranged from 4% to 11%. Black
women were more likely to face worse prognoses. (4) Karaye et al. stated
outcomes in Nigeria and found that 18.7% of women died due to any cause
in a median of 17 months. Maternal age below 20 years, hypotension at
presentation, and tachycardia were positively related to mortality.
Obesity and beta-blocker therapy was related to reduced risk of death.
(7) In 2020, ESC EORP PPCM registry results showed six-months outcomes:
overall mortality was 6%, and regional mortality differed. In European
countries, the mortality rate decreased to 4% in six months compared to
Middle Eastern countries, where the mortality rate was 10%. This ESC
EORP PPCM cohort was assessed for composite end-point (all-cause
mortality, LVAD implantation, and heart transplantation) in PPCM
patients with extended follow-up time. The death rate was 10.8%, and
one-year death-free survival was 97.1% (2.9 events per year). The
survival probability without a primary end-point was 11.9% in one year.
Our study’s event rate in one year was lower than the EORP PPCM
registry. (8) This could be explained by the higher rate of referred
patients. Mortality probably is higher in the course of initial acute HF
hospitalization. The availability of advanced HF therapies in our center
probably affects more favorable survival.
In our study, we analyzed the CMR data of this patient population. In
the literature, few studies present CMR data. Mouquet et al. analyzed 8
PPCM patients with CMR. LVEF measured by CMR correlated with
echocardiography. The authors did not observe morphological aspects of
LVNC or any other cardiomyopathies. CMR was re-performed in five
patients. Neither baseline nor six months control CMR demonstrated an
LGE pattern. (9) Marmursztejn et al. reported CMR results of two cases
where one patient exhibited LGE. (10) Ersboll and colleagues analyzed a
nationwide Danish cohort of 28 PPCM women with CMR: the mean LVEF was
62%, and one patient had LGE. The CMR was not performed in the early
phase of PPCM(11). Liang et al. showed three CMR parameters correlated
with recovery in PPCM: T1, T2, and extracellular volume (ECV). This
study was performed on 21 PPCM patients and 20 age-matched patients.
Although these parameters were related to LVEF recovery, ECV was the
only independent parameter that surmised LVEF recovery. (12)
In the study performed by Arora et al., ten patients were
retrospectively recruited, and their medical records paved the way for
diagnosing PPCM. LGE was presented in 4 patients, all of whom had HF
exacerbations during delivery. In addition, four patients had future
pregnancies, and two women had LGE. These two women had HF
decompensation during the following delivery(13).
This study reveals 25 patients’ baseline CMR results and seven control
CMR results. Patients who have reached the primary end-point did not
show a difference compared to the patients in whom the primary endpoint
did not occur. Three patients with LGE reached the primary end-point.
Two had sub-epicardial late enhancement; the first patient had an
arrhythmic event during a HF medication titration course. Although LV
systolic function improved during the follow-up, she experienced sudden
cardiac death on the 136 days. The second patient implanted with an ICD
had an appropriate shock for ventricular tachycardia. The third patient
with LGE needed heart transplantation. These limited data revealed that
PPCM with LGE had a poor prognosis, and sub-epicardial LGE exhibited
patients may more likely have ventricular arrhythmia. This information
may indicate that patients with sub-epicardial LGE are more likely to
have arrhythmic death, so early ICD implantation strategies could be
life-saving.
A few studies in the literature show trabeculations in LV consistent
with LVNC during pregnancy. These trabeculations are best studied with
CMR. In PPCM patients, a non-compaction cardiomyopathy phenotype was
reported in case reports. Rehfeldt et al. shared a case report that
suffered resuscitated cardiac arrest without past cardiac history. The
echocardiographic assessment showed very low LVEF (5%), and she had
LVAD surgery. She had prominent trabeculations compatible with LVNC
phenotype after LVEF recovered at three months, and LVAD was removed.
The NC/C ratio was not stated. (14)
Patel et al. reported two case reports claiming LVNC phenotype in PPCM
patients. In the first patient, the NC/C ratio was 3.2 according to
Jenni’s criteria and regressed to 2.5. The second patient had an
end-systolic NC/C ratio of 1.63; however, this ratio was inconsistent
with LVNC criteria. (15) Lea et al. presented a single case report: the
patient diagnosed with acute HF during pregnancy showed an enlarged left
ventricle and hypertrabeculation coherent with LVNC. After delivery, the
patient’s clinical situation worsened, and they needed heart
transplantation surgery. Explant material revealed LVNC properties. (16)
and Rajagopalan et al. identified five patients who met the clinical
definition of PPCM and LVNC imaging criteria. CMR was assessed in all
patients. Three of the five patients had sustained left ventricular
dysfunction; one had heart transplantation surgery, second had LVAD
bridge to transplantation. In two patients, LVEF improved by over
40%.(17)
The development of trabeculations in the LV during pregnancy is another
issue of discussion. Gati et al. evaluated 102 pregnant women and
performed TTE in the first and third trimesters. 26 (25.4%) patients
developed increased trabeculations; eight women revealed sufficient
trabeculations to fulfill the criteria for LVNC. During the postpartum
period, 19 (73%) women demonstrated complete resolution of the
trabeculations, and five showed a reduction in the trabeculated layer.
(18)
In our cohort, 25 women diagnosed with PPCM CMR were performed, and the
NC/C ratio was measured. Eighteen patients met the LVNC Peterson
criteria. Seven patients’ NC/C ratio was lower than 2.3 and did not
confirm other cardiomyopathies. In Nine of eighteen LVNC phenotype
patients, LVEF recovered. However, three patients with this phenotype
reached the primary end-point (two death and one heart transplantation).
In Seven of the 18 patients, CMR was re-performed, and in four patients
NC/C ratio was over 2.3, consistent with LVNC. Three of Four patients’
NC/C ratio decreased, and in one patient NC/C ratio increased.
Studies in the literature and our paper raise the question of whether
patients with LVNC who presented with first-time HF during pregnancy
were misdiagnosed with peripartum CMP. PPCM is unknown idiopathic
cardiomyopathy and has to be differentiated from other causes of HF.
Thus a careful examination of patients with PPCM should be done, and CMR
should be performed to exclude other forms of cardiomyopathies. Further
research on the development of trabeculations during pregnancy is
needed.