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\begin{document}

\title{The outcome of Peripartum Cardiomyopathy Patients-Single Center
Experience}



\author[1]{Emre Demir}%
\author[1]{Naim Ceylan}%
\author[1]{Selen Bayraktaroğlu}%
\author[1]{Akın Çinkooğlu}%
\author[1]{Aytaç Candemir}%
\author[1]{Yeşim B. Candemir}%
\author[1]{Mustafa Talha Güneş}%
\author[1]{Şevket Yeniyol}%
\author[1]{Elfin B. Yılmaz}%
\author[1]{Mehdi Zaoghi}%
\author[1]{Azem Akıllı}%
\author[1]{cemil gurgun}%
\author[1]{Sanem Nalbantgil}%
\affil[1]{Ege Universitesi}%


\vspace{-1em}



  
  \date{June 16, 2024}


\begingroup
\let\center\flushleft
\let\endcenter\endflushleft
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\endgroup





\selectlanguage{english}
\begin{abstract}
\textbf{Objective:} Peripartum cardiomyopathy (PPCM) diagnosis made by
excluding identifiable causes of heart failure (HF) and occurs end of
the pregnancy or during the postpartum period of five months. It
presents a clinical HF spectrum with left ventricular systolic
dysfunction. \textbf{Background:} The purpose of this study is to
retrospectively evaluate the clinical characteristics, cardiac magnetic
resonance (CMR) imaging features, and end-points consisting of left
ventricle recovery, left ventricular assist device implantation, heart
transplantation, and all-cause mortality. \textbf{Method:} Outpatient HF
records between 2008 to 2021 were screened. Thirty-seven patients were
defined as PPCM. Twenty-five patients had CMR evaluation at the time of
diagnosis, and six patients were re-evaluated with CMR.
\textbf{Results:} The mean age was 30.5\selectlanguage{ngerman}±5.6 years, and the mean LVEF was
28.2±6.7\%. In thirteen(35.7\%) patients, LVEF recovered during the
follow-up course. The median recovery time was 281(IQR {[}78-358{]})
days. LVEF on CMR was 35.3±10.5, and three patients exhibited late
gadolinium enhancement(LGE) patterns. Sub-endocardial and mid-wall
uptake pattern types were detected. 18(75\%) patients met the Petersen
left ventricle non-compaction cardiomyopathy(LVNC) criteria. Patients
with NC/C ratio lower than 2.3 had lower LVEDVi and LVESVi
(124.9±35.4,86.4±7.5, p=0.003;86.8±34.6,52.6±7.6, p=0.006),
respectively. The median follow-up time was 2129 (IQR {[}911-2634{]})
days. The primary endpoint-free one-year survival was 88.9\%(event rate
11.1\%), and five-year survival was 75.7\%(event rate 24.3\%).
\textbf{Conclusion:} In a retrospective cohort of PPCM patients, 35.7\%
of patients' LVEF recovered, and the primary end-point of free-five-year
survival was 75\%. Twenty-five patients were assessed with CMR; three of
four met the Petersen CMR-derived LVNC at initial evaluation.%
\end{abstract}\selectlanguage{ngerman}%



\sloppy


\textbf{TITLE}

\textbf{The outcome of Peripartum Cardiomyopathy Patients-Single Center
Experience}

Emre Demir \textsuperscript{a}, MD, Naim Ceylan\textsuperscript{b}, MD,
Selen Bayraktaro\selectlanguage{polish}ğ\selectlanguage{english}lu\textsuperscript{b}, MD, Ak\selectlanguage{polish}ı\selectlanguage{english}n
\selectlanguage{ngerman}Çinkoo\selectlanguage{polish}ğ\selectlanguage{english}lu\textsuperscript{b},MD, Ayta\selectlanguage{ngerman}ç Candemir \textsuperscript{a}, MD,
Ye\selectlanguage{polish}ş\selectlanguage{english}im B. Candemir\textsuperscript{a} , MD, Mustafa Talha
G\selectlanguage{ngerman}üne\selectlanguage{polish}ş\selectlanguage{english}\textsuperscript{a}, MD, \selectlanguage{polish}Ş\selectlanguage{english}evket Yeniyol\textsuperscript{c} , Msc,
Elfin B. Y\selectlanguage{polish}ı\selectlanguage{english}lmaz\textsuperscript{c}, MSc, Mehdi Zoghi\textsuperscript{a},
MD, Azem Ak\selectlanguage{polish}ı\selectlanguage{english}ll\selectlanguage{polish}ı\selectlanguage{english}\textsuperscript{a}, MD, Cemil G\selectlanguage{ngerman}ürgün\textsuperscript{a},
MD, Sanem Nalbantgil\textsuperscript{a}, MD

\textsuperscript{a} Ege University School of Medicine Cardiology
Department

\textsuperscript{b} Ege University School of Medicine Radiology
Department

\textsuperscript{c}Ege University School of Medicine

\textbf{Abstract: 250 words}

\textbf{Total word count:}

\textbf{A number of tables and figures:}

\textbf{Disclosures:}

None

\textbf{Study funding:}

None

\textbf{Corresponding author:} Emre Demir MD

e-mail address:\emph{emre.demir@ege.edu.tr/emre.demir.ege@gmail.com}

Adress: Kaz\selectlanguage{polish}ı\selectlanguage{english}m Dirik Mahallesi Ankara Caddesi, Ege \selectlanguage{ngerman}Üniversitesi T\selectlanguage{polish}ı\selectlanguage{english}p
Fak\selectlanguage{ngerman}ültesi Kardiyoloji Anabilim Dal\selectlanguage{polish}ı \selectlanguage{english}Bornova-\selectlanguage{polish}İ\selectlanguage{english}zmir/Turkey 35100

Telephone number: +90 (544) 226 25 03/+90 (232) 390 49 15

Fax number: + 90 (232) 390 32 87

Twitter handle:EmreDemirEge

Ege University School of Medicine Cardiology Department

Emre Demir Orchid number= 0000-0001-7552-8967

Naim Ceylan Orchid number = 0000-0003-1128-0573

Selen Bayraktaro\selectlanguage{polish}ğ\selectlanguage{english}lu Orchid number = 0000-0001-9167-9474

Ak\selectlanguage{polish}ı\selectlanguage{english}n \selectlanguage{ngerman}Çinkoo\selectlanguage{polish}ğ\selectlanguage{english}lu Orchid number = 0000-0003-3396-3949

Eilf \selectlanguage{polish}İ\selectlanguage{english}lkay Y\selectlanguage{ngerman}üce Ersoy Orchid number = 0000-0001-9078-0941

Aytaç Candemir Orchid number = 0000-0002-5872-180X

Ye\selectlanguage{polish}ş\selectlanguage{english}im B. Candemir Orchid number = 0000-0001-5926-8499

Mustafa Talha G\selectlanguage{ngerman}üne\selectlanguage{polish}ş \selectlanguage{english}Orchid number = 0000-0001-6933-9414

\selectlanguage{polish}Ş\selectlanguage{english}evket Yeniyol Orchid number = 0000-0002-2775-4406

Elfin B. Y\selectlanguage{polish}ı\selectlanguage{english}lmaz Orchid number = 0000-0002-8584-5832

Mehdi Zoghi Orchid number= 0000-0002-8156-2675

Azem Ak\selectlanguage{polish}ı\selectlanguage{english}ll\selectlanguage{polish}ı \selectlanguage{english}Orchid number = 0000-0003-1383-8024

Cemil G\selectlanguage{ngerman}ürgün Orchid number = 0000-0001-9593-1630

Sanem Nalbantgil Orchid number = 0000-0002-9798-9796

\textbf{Ethic committee and approval}

The Ege University institutional review board approved the study, and
informed consent has been taken from the subjects or first-degree
relatives.

Ege University aproval date and decision number: 03.09.2021-E.292544

\textbf{The Outcome of Peripartum Cardiomyopathy Patients-Single Center
Experience}

\textbf{ABSTRACT:}

\textbf{Objective:} Peripartum cardiomyopathy (PPCM) diagnosis made by
excluding identifiable causes of heart failure (HF) and occurs end of
the pregnancy or during the postpartum period of five months. It
presents a clinical HF spectrum with left ventricular systolic
dysfunction.

\textbf{Background:} The purpose of this study is to retrospectively
evaluate the clinical characteristics, cardiac magnetic resonance (CMR)
imaging features, and end-points consisting of left ventricle recovery,
left ventricular assist device implantation, heart transplantation, and
all-cause mortality.

\textbf{Method:} Outpatient HF records between 2008 to 2021 were
screened. Thirty-seven patients were defined as PPCM. Twenty-five
patients had CMR evaluation at the time of diagnosis, and six patients
were re-evaluated with CMR.

\textbf{Results:} The mean age was 30.5±5.6 years, and the mean LVEF was
28.2±6.7\%. In thirteen(35.7\%) patients, LVEF recovered during the
follow-up course. The median recovery time was 281(IQR {[}78-358{]})
days. LVEF on CMR was 35.3±10.5, and three patients exhibited late
gadolinium enhancement(LGE) patterns. Sub-endocardial and mid-wall
uptake pattern types were detected. 18(75\%) patients met the Petersen
left ventricle non-compaction cardiomyopathy(LVNC) criteria. Patients
with NC/C ratio lower than 2.3 had lower LVEDVi and LVESVi
(124.9±35.4,86.4±7.5, p=0.003;86.8±34.6,52.6±7.6, p=0.006),
respectively. The median follow-up time was 2129 (IQR {[}911-2634{]})
days. The primary endpoint-free one-year survival was 88.9\%(event rate
11.1\%), and five-year survival was 75.7\%(event rate 24.3\%).

\textbf{Conclusion:} In a retrospective cohort of PPCM patients, 35.7\%
of patients' LVEF recovered, and the primary end-point of free-five-year
survival was 75\%. Twenty-five patients were assessed with CMR; three of
four met the Petersen CMR-derived LVNC at initial evaluation.

\textbf{KEYWORDS:}

Peripartum cardiomyopathy

Non-compaction cardiomyopathy

Cardiac magnetic resonance imaging

\textbf{ABBREVIATIONS-ACRONYMS:}

ACE-i: Angiotensin-converting enzyme inhibitor

ARB: Angiotensin receptor blocker

CI: Confidence interval

CM: Cardiomyopathy

CMR: Cardiac magnetic resonance

DCM: Dilated cardiomyopathy

HF: Heart failure

HR: Hazard ratio

LGE: Late gadolinium enhancement

LVEDd: Left ventricular end-diastolic diameter

LVEDV: Left ventricular end-diastolic volume

LVEDV(i): Left ventricular end-diastolic volume index

LVEF: Left ventricular ejection fraction

LVESd: Left ventricular end-systolic diameter

LVESV: Left ventricular end-systolic volume

LVESV(i): Left ventricular end-systolic volume index

LVmass: Left ventricular mass

LVmass(i): Left ventricular mass index

LVNC: Left ventricular non-compaction cardiomyopathy

MACE: Major advanced cardiovascular event

PPCM: Peripartum cardiomyopathy

TTE: Transthoracic echocardiography

\textbf{BACKGROUND/INTRODUCTION:}

The European Society of Cardiology Working group accepted PPCM as
idiopathic cardiomyopathy (CM) with unknown pathophysiology and agreed
as different CM from other types of cardiomyopathies. (1) PPCM incidence
varies worldwide concerning ethnic and regional differences. The
reported incidence rates have increased awareness of PPCM in the recent
decade. PPCM may present with cardiogenic shock, acute HF, ventricular
arrhythmias, peripheric embolism, and may have complete recovery. PPCM
is a qualified instantaneous emerging clinical spectrum with a high
probability of recovery than other cardiomyopathies. (2)

The diagnosis is made by excluding other identifiable causes of HF. It
occurs towards the end of the pregnancy or during the postpartum period
of five months presenting as HF clinical spectrum with left ventricular
systolic dysfunction of LVEF\textless{}45\%. There are no specific
findings of PPCM; the diagnosis is based on clinical findings. (1)

CMR enables better visualization of cardiac morphology and functions and
may show the diagnostic morphological characteristics of
cardiomyopathies. In this paper, we aimed to evaluate clinical
characteristics, CMR features, and relationship with endpoints that
consist; of left ventricle recovery, left ventricular assist device
implantation, and all-cause of mortality.

\textbf{METHODS:}

The Ege University institutional review board approved the study, and
informed consent has been taken from the subjects or first-degree
relatives. Patients with HF admitted to HF outpatient clinics between
January 2008-May 2021 were included in this study (Figure-1). The
diagnosis of PPCM was based on European Society of Cardiology position
paper recommendations. (1) The clinical, echocardiographic, and CMR data
of these patients' analyses were assessed retrospectively. Clinical data
were collected from the university medical records and the phone call of
the patients or relatives.

Echocardiography data includes left ventricular dimensions,
interventricular thickness, LVEF, systolic pulmonary artery pressure
(SPAP), and valvular assessment. Qualified CMR assessed patients to
visualize cardiac dimension measurements, CMR functional analysis, and
fibrosis with late gadolinium enhancement (LGE).

\textbf{Cardiac magnetic resonance imaging assessment:}

Cardiac magnetic resonance imaging was performed with 1.5 tesla or
3.0-tesla unit scanners (Amira and Verio, Siemens Healthineers,
Erlangen, Germany). Patients were scanned with the electrocardiogram
(ECG), triggering a 16-channel surface phased array of body coils.
Briefly, 10 to 12 consecutive short-axis images covering the entire LV
and 2-, 3-, and 4-chamber long-axis images were acquired with a cine
steady-state free precession sequence (SSFP) to assess myocardial
function mass and quantification of non-compaction. Two-dimensional LGE
images were acquired in short axis, 2, and 4 chamber views by
phase-sensitive inversion recovery sequence (PSIR) ten to 15 min after
0.2 mmol/kg gadolinium contrast agent injection. Cardiac volume,
function, and mass on cardiac images were analyzed with software; Medis
medical imaging systems-Medis Suite 3.1 (Leiden, Netherlands) by three
radiologists for disagreements on data between two readers. A consensus
agreement was achieved with the third expert opinion. The non-compacted
and compacted ratio calculated distal to the papillary muscle that any
segment reveals the highest proportion except the left ventricular apex.
LGE distribution was reviewed in long and short axis contrast-enhanced
images, and LGE presence was accepted in short and long-axis imaging
planes. LGE distributions are visually classified as sub-endocardial,
mid-myocardial (mid-wall), sub-epicardial, and right ventricular
insertion involvement. Two radiologists determined the LGE distribution
pattern; a third senior radiologist was consulted when there was
disagreement.

\textbf{Survival analysis and end-points:}

The primary end-point of our study was a composite end-point of major
cardiovascular events comprising left ventricular assisted device
implantation, heart transplantation, and all-cause mortality. LV
systolic function recovery is defined as improving
LVEF\textgreater{}10\% and increasing over 40\%. A total of 37 patients
were included in the study.

\textbf{Statistical Analysis:}

\selectlanguage{english} Statistical analysis was performed with Medcalc 19.0 (R) and SPSS
version 25.0 software (IBM SPSS Statistics, IBM Corporation, Armonk, New
York) statistical program. Distribution normality was tested by the
Shapiro Wilk test. Continuous variables are calculated as mean, SD, or
median (IQR), and categorical variables as counts and percentages.
Comparisons between groups were performed with a two-sided
Student\emph{t} -test, Wilcoxon-Mann-Whitney U test, and chi-square or
Fisher exact test for categorical variables. Values of p \textless{}0.05
were accepted to be statistically significant.

The follow-up duration is determined using the index date to the first
MACE date or the last follow-up of patients. Survival curves compared
with the log-rank (Mantel-Cox) test for defined primary end-points.

\textbf{RESULTS:}

Thirty-seven patients that met the ESC PPCM criteria were included in
the study. The mean age was 30.5\selectlanguage{ngerman}±5.6 years. All patients first presented
with HF symptoms; six patients also had left ventricular thrombus, and
two had a concomitant acute pulmonary embolism.

Six patients (16.2\%) had a diagnosis of hypertension, four patients had
preeclampsia before the diagnosis of HF, seven (18.9\%) patients had
diabetes mellitus, and three (8.1\%) patients had a smoking history
before pregnancy. Four (10.8\%) patients reported a family history of HF
related to non-ischemic CM. Two (8.3\%) patients' rhythm was atrial
fibrillation, two patients had left bundle branch block (LBBB), one
patient presented with right bundle branch block (RBBB) at baseline, and
eight (21.6\%) patients had implanted ICD.

Of the PPCM patients, 28 (80\%) were treated with ACE-i or ARB, 33
(94.2\%) patients with beta-blocker, and 25 (75.3\%) patients were on
mineralocorticoid receptor antagonists during the follow-up period.
Three patients who presented acute HF were treated with bromocriptine
(Table 1).

The mean baseline LVEF was 28.2±6.7\%, the mean left ventricular
end-diastolic diameter (LVEDd) was 59.6±7.4 mm, and the left ventricular
end-systolic diameter (LVESd) was 50.1±8.5 mm. Twenty-two (62.9\%)
patients had moderate or severe functional mitral regurgitation, and 15
(42.9\%) patients had moderate or severe functional tricuspid
regurgitation. On the last follow-up, 24 patients' echocardiography was
re-assessed, and the mean LVEF was 39.9±13.5\%. During the follow-up
period, the mean LVEF change was 11.7±15.7\% (p=0.001) (Table 2).

In thirteen (35.7\%) patients, left ventricular systolic function
recovered during the follow-up course. The median recovery time was
281(IQR {[}78-358{]}) days.

Cox regression analysis did not demonstrate a significant predictor for
recovery.

\textbf{Cardiac magnetic resonance imaging}

Cardiac magnetic resonance imaging was performed on 25 patients. CMR
measured mean LVEF was 35.3±10.5, mean LVEDd was 58.8±8.0 mm, and mean
LVESd was 50.4 ±10.4 mm. Seven (28\%) patients LVEDd was in the normal
range. Despite the decreased LVEF and enlarged left ventricle, the mean
volumes, cardiac output, and cardiac index were preserved.

Three patients exhibited late gadolinium enhancement (LGE) patterns.
Sub-endocardial and mid-wall uptake pattern types were detected, one
patient with subendocardial LGE experienced sudden cardiac death in a HF
medication titration course, and the second patient experienced
ventricular tachycardia with appropriate ICD shock. The third patient
with mid-wall LGE pattern type needed heart transplantation surgery.

All patients demonstrated trabeculation at least in one left ventricular
segment, and trabeculations were mostly detected in lateral and inferior
segments. The mean non-compacted to compacted (NC/C) ratio was
2.73±0.88, and 18 (75\%) patients met the Petersen non-compaction
cardiomyopathy criteria. Patients were also compared regarding NC/C
ratio; patients with NC/C ratio lower than 2.3 had lower LVEDV(i) and
LVESV(i) (124.9±35.4, 86.4±7.5, p=0.003; 86.8±34.6, 52.6±7.6, p=0.006),
respectively.

Seven patients underwent a second CMR to evaluate the left ventricle
volumes and cardiac function. Four patients with NC/C ratio over 2.3 had
a non-compaction cardiomyopathy phenotype at the second CMR examination.
In all seven patients who underwent CMR, LVEF increased; the mean change
was 13.85±12.5 (p=0.0035) (Table 3).

Survival data were available for all patients. The median follow-up time
was 2129 (IQR {[}911-2634{]}) days. Ten (27\%) patients experienced
primary end-point; five (13.5\%) patients experienced death, two (5.4\%)
patients underwent left ventricular assisted device implantation, and
three (8.1\%) patients experienced heart transplantation surgery. The
primary end-point occurrence median time was 786 (IQR {[}167-1498{]})
days-(Figure 2).

The primary end-point free one-year survival was 88.9\% (event rate
11.1\%), and five-year survival was 75.7\% (event rate 24.3\%) (Figure
3).

\textbf{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\textgreater{}\%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.

\textbf{CONCLUSION:}

This study evaluated 37 PPCM patients. 46\% of the patients' left
ventricle systolic function recovered. In five years, 25\% of patients
reached the primary end-point. Most of the patients were evaluated by
CMR, and 75\% met the criteria of left ventricle non-compaction
cardiomyopathy. Three patients exhibited LGE, and two of them reached
the study's primary end-point. Our study highlights the importance of
CMR imaging in this patient population. First, it is essential to
diagnose the disease: LVNC may be the underlying etiology for the
development of HF. Second, LGE presence is a marker of poor prognosis.

\textbf{LIMITATIONS:}

A limited number of patients were included in our study because PPCM is
a rare CM. This study was in retrospective case-control series design
and represented the single-center experience. The study included
patients referred to a tertiary HF center, so a number of patients' data
were missing. Two radiologists re-evaluated CMR images, but in twelve
years, CMR imaging modalities' quality has changed. All patients' CMR
morphological features were evaluated, but 20\% of the functional
analysis was missing.

\textbf{HIGHLIGHTS:}

1-The recovery rate of patients with peripartum cardiomyopathy is higher

2-Five years major cardiovascular event rate was 24.6\% in peripartum
cardiomiyopathy patients.

3-CMR imaging results revealed 75\% of the patients met the Petersen
LVNC criteria. This finding suggest the underlying cause of peripartum
cardiomyopathy may be LVNC.

4- The presence of late gadolinium enhancement is a sign of poor
prognosis in PPCM patients.

\textbf{Declaration of Interests:} No conflict of interest.

\textbf{Funding:} No funding.

\textbf{FIGURE LEGENDS}

\textbf{Figure 1: Flow chart of study patients/consort diagram of
peripartum cardiomyopathy patients.}

ARVC=Arrhytmogenic right ventricular; CMR=Cardiac magnetic resonance;
cardiomyopathy; C=compacted myocardium; NC= non-compacted myocardium;
NC/C ratio= ratio of the non-compacted segment to compacted segment of
the myocardium.

\textbf{Figure 2: The peripartum cardiomyopathy patients' primary
endpoint occurrence median time distribution box-whisker plot.}

The primary end-point occurrence median time was 786 (IQR
{[}167-1498{]}) days.

\textbf{Figure 3: Kaplan Meier survival analysis of the peripartum
cardiomyopathy patients.}

Kaplan Meier survival analysis estimates free of major cardiovascular
events in the PPCM patients.

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