Definition
The Heart Failure Association
(HFA) of the European Society of Cardiology (ESC) has recently published a
revised definition of PPCM
Peripartum cardiomyopathy (PPCM)
is a life-threatening disease of the heart of unknown cause, which:
- in previously healthy patients
- occurs during the last month of pregnancy, at birth or in the first postpartum months.
- The left ventricular ejection fraction (LVEF) is usually less than 45% without a clearly identifiable cause.
- The clinical picture shows rapidly progressive myocardial insufficiency, often associated with dilation of all ventricles
Epidemiology
Frequencies for PPCM vary between:
(per live birth)
- 1 in 2500-4000 in the US,
- 1 in 1000 in South Africa and
- 1 in 300 in Haiti
- 1 in 1500-2000 in Europe, Asia and Australia
Explanations for the different
frequencies of the PPCM in the different geographic regions could be:
- The ethnic background
- Different living conditions and habits
- Sensitivity to the disease
- The different inclusion criteria
Risk factors
- Hypertensive conditions in pregnancy
- Nicotine consumption,
- An increased age at the time of pregnancy
- A multiparity and multiple pregnancy
Can be considered as potential
risk factors while gestational diabetes is not associated with PPCM.
It has also been shown that
approximately 16% of PPCM patients have a positive family history of
cardiomyopathy.
Recent studies show that mutations
in genes, eg. Titin, troponin C and myosin heavy chain 7 (MYH7), which are
known to cause cardiomyopathies, are more common in families with PPCM and DCM
disorders.
The cardiac stress during
pregnancy could have led to the unmasking of genetic cardiomyopathies.
This finding again illustrates the
difficulty of distinguishing a PPCM from an existing but undiagnosed cardiomyopathy,
which may have a worse prognosis than PPCM.
Pathomechanisms of PPCM
In an experimental model of PPCM
in mice it could be shown that:
- Increased oxidative stress leads to cleavage of the breastfeeding hormone prolactin by cathepsin D into a pro-apoptotic and anti-angiogenic 16kDa subform.
- The 16kDa prolactin damages the endothelium and thus the microcirculation in the myocardium.
- Pharmacological inhibition of prolactin by the dopamine D2 receptor agonist bromocriptine successfully prevented the development of PPCM in various mouse models, thus supporting the hypothesis that the 16kDa prolactin might be causally involved in PPCM.
- The 16kDa prolactin-induced microRNA, miR-146a, is largely responsible for the endothelium-damaging pro-apoptotic and anti-angiogenic properties of 16kDa prolactin.
- In cardiomyocytes, miR-146a reduces the expression of the ErbB4 receptor, which is essential for survival, metabolism, and endothelial communication.
- Neutralization of miR-146a by antisense technology largely prevented PPCM in the mouse model while allowing normal prolactin signaling because the mice were able to suckle their cubs
As part of the normal changes in
late pregnancy it comes, For example, an increased release of sFlt1 from the
placenta. SFlt1 is an anti-angiogenic factor that inhibits vascular endothelial
growth factor (VEGF). In multiple pregnancies and pre-eclampsia, serum levels
are particularly high for sFlt1, but normally normalize rapidly after childbirth,
while they remain elevated in PPCM patients.
It now appears that in the
maternal heart, pro-angiogenic factors such as VEGF must be expressed more to
protect the organ from these anti-angiogenic factors. This hypothesis suggests
that in a mouse model combined treatment with recombinant VEGF and the
prolactin blocker bromocriptine could prevent PPCM.
Diagnosis
The clinic of PPCM is often
characterized by a left-leading cardiac decompensation with dyspnea symptoms,
wet fine-bubble rattle sounds and a third heart sound in the auscultation.
There may also be signs of global decompensation with peripheral edema and
anasarca. In some cases, a recent secondary mitral valve insufficiency can be
detected.
In almost all cases a significant
increase of the NT-proBNP is found in the laboratory investigation. In
contrast, other cardiac markers such as troponin T or creatine kinase (CK) are
at most slightly elevated
Echocardiography is regarded as
the most important apparatus of investigation. In the case of a PPCM, this
typically shows a clear limitation of the global systolic left ventricular
function with an LVEF <45%.
Radiographic signs of cardiac
decompensation, such as pulmonary congestion signs and pulmonary edema with
pleural effusions are often found in the chest X-ray
Cardiac magnetic resonance imaging
(MRI) is also useful for the differential diagnosis of PPCM such as Myocarditis.
Invasive cardiac catheterization
and biopsy sampling are rarely used.
MANAGEMENT
In the treatment of a PPCM must be
noted:
- Stable vs unstable patients
- Präpartale vs postpartum CM
Unstable patients with PPCM
Signs of cardiogenic shock require
intensive care treatment:
- diuretics
- Vasodilators at RR> 110 mmHg (hydralazine at pregnancy and NG postpartum(
- Invasive or non-invasive ventilation
- Catecholamines at low RR levels should be used on a restive basis as there is evidence of adverse effects in PPCM patients.
- Calcium sensitizer Levosimendan, unlike catecholamines, seems safe and can be considered.
- If therapy-refractory shock is present, the use of a mechanical circulatory system may be required:
- Percutaneous microaxial pump (Impella®) in isolated LV failure.
- Impella® in combination with venoarterial extracorporeal membrane oxygenation ECMO in case of ventricular failure
- In the case of a pre-existing pregnancy an emergency childbirth by means of cesarean section is indicated
- Hemodynamic stabilization is followed by gradual weaning.
Stable patients with PPCM
Pregnancy does not require the
termination of pregnancy; vaginal spontaneous childbirth is recommended.
Drug therapy:
- B-blocker (metoprolol in pregnancy is preferred)
- Diuretic (loop diuretics)
- For reducing afterload, if necessary, hydralazine
- fetal lung maturation should be induced
Therapy After childbirth:
Oral heart failure therapy
according to the guideline of the ESC (European Society of Cardiology):
- B-blocker
- ACE inhibitor/angiotensin receptor blocker (ARB): in maximum dissolved dosage
- At EF <40%: mineral corticosteroid receptor antagonists (MRAs) prefer eplerenone because of the most favorable hormonal side effects
- in further symptomatic patients despite o.g. Therapy is the conversion of ACE/ARB therapy to angiotensin receptor neprilysin inhibitor (ARNI) Entresto® recommended
- The additional administration of ivabradine is effective at HF> 70/min despite the maximum dose of B-blocker.
- Diuretics for edema or signs of pulmonary congestion are recommended, with a reduction to the lowest possible dosage recommended
- At full recovery, the therapy should be continued for at least 6 months. Then a gradual termination of the therapy is possible under biannual clinical and echocardiographic controls.
Initially the termination
of MRA, then the ACE inhibitor/ARB/ARNI, and ultimately the beta-blocker.
Diuretics are already discontinued at the time of recovery.
Bromocriptine for the treatment of
peripartum cardiomyopathy: a multicentre randomized study 03/2010-08/2016
Methods and results
In this multicenter trial, 63 PPCM
patients with left ventricular ejection fraction (LVEF) ≤35% were randomly
assigned to:
- short-term (1W: bromocriptine, 2.5 mg, 7 days) or
- long-term bromocriptine treatment (8W: 5 mg for 2 weeks followed by 2.5 mg for 6 weeks)
- in addition to standard heart failure therapy.
- The primary endpoint was LVEF change (delta) from baseline to 6 months assessed by magnetic resonance imaging. Bromocriptine which is well tolerated.
- Left ventricular ejection fraction increased from 28 ± 10% to 49 ± 12% with a delta-LVEF of + 21 ± 11% in the 1W-group, and from 27 ± 10% to 51 ± 10% with a delta-LVEF of + 24 ± 11% in the 8W-group (delta-LVEF: P = 0.381(
- Full recovery (LVEF ≥ 50%) was present in 52% of the 1W and in 68% of the 8W group
- no differences in secondary endpoints between both groups (hospitalizations for heart failure: 1W: 9.7% vs. 8W: 6.5%, P = 0.651). The risk within the 8W-group to fail full-recovery after 6 months tended to be lower. No patient in the study needed a heart transplantation, LV assist device or died.
- Compared to data from non-bromocriptine-treated PPACM patients from the American IPAC Registry (Investigation on Pregnancy-Associated Cardiomyopathy), it can be assumed that there is a clear benefit for bromocriptine therapy in women with EF <35% (heart transplantation, cardiac assistive system, EF <35% or death 37% of all patients in the IPAC registry vs. 2.7% of all patients in bromocriptine study)
Conclusion
Bromocriptine treatment was
associated with a high rate of full LV recovery and low morbidity and mortality
in PPCM patients compared with other PPCM cohorts not treated with
bromocriptine. 1W and 8W treatment suggesting that 1-week addition of
bromocriptine to standard heart failure treatment is currently in the 8W group.
Recently, the so-called BOARD-schema for the pharmacological treatment of PPCM was developed at the Hannover
Medical School:
- Bromocriptine
- Oral heart failure medication
- Prophylactic Anticoagulation (to prevent thromboembolic events as a side effect of bromocriptine therapy)
- VasoRelaxanten for reducing the afterload
- Diuretics in low dosage as possible
For patients with EF <35%, the temporary
prescription of LifeWest is indicated for 3-6 months due to the high risk of
ventricular tachycardia.
In case of ventricular tachycardia/ventricular
fibrillation, the implantation of ICD is indicated.
Although the EF persists <35% at 6 months,
implantation of a prophylactic ICD or CRT-D system is indicated.
Prognosis
Overall good prognosis:
- 50% complete recovery with EF> 55%
- 35-40% partial recovery, EF improvement of at least 10% and an NYHA class
Is a new pregnancy possible?
Follow-up pregnancy after previous
PPCM is associated with increased maternal and fetal risk.
However, a follow-on pregnancy is
not excluded after complete recovery.
In persistent LV dysfunction,
women have an unfavorable prognosis (with respect to mortality, LV dysfunction,
and NYHA class) when re-pregnant
Heart failure therapy in pregnancy
and lactation?
ACE inhibitors/ARB/ARNI/MRA and
ivabradine are contraindicated during pregnancy and lactation
B-blocker (metoprolol) may be given
Diuretics are restrictive and
should be given only if clearly indicated.
Written by: Ayman Zoaa
I’m a resident doctor living in Bremerhaven-Germany, my goal here is to explain medical stuff as easy and practical as possible. My second purpose is to help those who are trying to begin specializing in Germany.About my profession, I’m 30 years old, was born in Syria on 1989, I studied medicine at the University of Aleppo between 2007 and 2013, then I traveled to Germany and began my actual work before about 3 Years. I have got my medicine certificate recognized in Germany after I had made the recognition test and the medical language test.I’m specializing in internal medicine, and then I’ll proceed to gastroenterology, and hopefully endocrinology.I find writing interesting, and it also helps me to keep my information up to date, what we- medical people - need.Let us keep in touch through singing up, and through the contact-from, i will answer your Questions gladly
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