Skip to content
How It Works
Explore
Resources Ask a Question
Who It's For
Patients Caregivers Providers
Log In Ask a Question
PubMed This is a summary of 17 peer-reviewed journal articles Updated
Cardiology

The Biology of PPCM: Why the Heart Weakens

At a Glance

Peripartum Cardiomyopathy (PPCM) is a type of heart failure triggered late in pregnancy or postpartum. It is often caused by a combination of oxidative stress altering the prolactin hormone and genetic vulnerabilities like TTN mutations. It is diagnosed using echocardiograms and BNP blood tests.

Understanding the biology of Peripartum Cardiomyopathy (PPCM) can help demystify the sudden changes in your body. It is not a result of anything you did; rather, it is a complex biological event triggered by the unique environment of late pregnancy and the early postpartum period [1][2].

The “Bad Actor”: 16kDa Prolactin

One of the leading theories behind PPCM involves a hormone you likely know well: prolactin. Prolactin is essential for breastfeeding, but in some women, oxidative stress—a type of cellular “wear and tear”—causes a change in how this hormone is processed [3].

Normally, prolactin exists in a healthy 23kDa size. However, due to oxidative stress, an enzyme called cathepsin D can “cleave” or break this hormone into a smaller, toxic fragment known as 16kDa prolactin [3]. This fragment acts as a “bad actor” in the body: it damages the small blood vessels in the heart and triggers cell death in the heart muscle, leading to the weakening of the heart [3][4].

The Role of Genetics

While hormones play a major role, your DNA may also be a factor. Many women with PPCM carry a genetic variant in the TTN gene, which provides instructions for making a protein called titin [5][6]. Titin acts like a molecular spring that helps your heart muscle contract and relax. If you have a TTN mutation (specifically a “truncating variant”), your heart may be more vulnerable to the stresses of pregnancy, making it more likely to develop cardiomyopathy [7][8].

How PPCM is Diagnosed

PPCM is a diagnosis of exclusion. This means your doctors will first look for other causes—like a viral infection, a heart valve problem, or a pre-existing condition—and only when no other cause is found will they confirm PPCM [9][10].

Key Diagnostic Tools

  1. Echocardiogram (Echo): This is an ultrasound of your heart. The most important number on this report is the Left Ventricular Ejection Fraction (LVEF). PPCM is typically diagnosed when the LVEF is less than 45% [9][11].
  2. Global Longitudinal Strain (GLS): You may see this on your report. It is a more sensitive way to measure heart function. It tracks how the heart muscle fibers shorten and can sometimes detect heart strain even before the LVEF drops significantly [12][13].
  3. Biomarkers (Blood Tests):
    • BNP and NT-proBNP: These are proteins released when your heart is “stretched” or working too hard [14][15]. High levels (often $\ge$125 pg/mL for NT-proBNP) help doctors confirm that your symptoms are related to heart failure [16][17].

Technical Terms to Watch For

When you look at your medical records, keep an eye out for these terms:

  • Cardiomyopathy: Literally translates to “disease of the heart muscle.” It means your heart muscle has become enlarged, thick, or rigid [9].
  • Idiopathic: This simply means the cause is currently unknown (standard for PPCM) [9].
  • Systolic Dysfunction: This means the heart is having trouble pumping blood out to the body [9].
  • Non-ischemic: This confirms that your heart failure was not caused by a heart attack or blocked arteries [9].

By understanding these biological markers, you can more effectively track your progress and discuss your recovery with your cardiology team.

Common questions in this guide

What causes Peripartum Cardiomyopathy (PPCM)?
PPCM is caused by a complex biological response during late pregnancy or the early postpartum period. Key factors include oxidative stress that alters the prolactin hormone into a form that damages the heart, often combined with an underlying genetic vulnerability.
How does prolactin affect the heart in PPCM?
Prolactin is a hormone needed for breastfeeding. In some women, oxidative stress breaks it down into a smaller 16kDa fragment. This toxic fragment damages small blood vessels in the heart and causes heart muscle weakness.
Can genetics increase my risk for developing PPCM?
Yes, many women with PPCM carry a mutation in the TTN gene, which provides instructions for a heart protein called titin. This mutation can make the heart muscle more vulnerable to the physical stresses of pregnancy.
How is PPCM diagnosed?
Doctors diagnose PPCM by ruling out other causes of heart failure. They use an echocardiogram to check if the heart's pumping ability (Ejection Fraction) is below 45% and blood tests to look for elevated heart stress markers like NT-proBNP.
What does the Ejection Fraction (LVEF) number mean?
Left Ventricular Ejection Fraction (LVEF) is a measurement taken during an ultrasound of your heart. It shows how well your heart pumps blood with each heartbeat. An LVEF below 45 percent is a primary indicator used to diagnose PPCM.

Questions for Your Doctor

5 questions

  • •Since PPCM can have a genetic component, should I be tested for the TTN (titin) mutation, and should my first-degree relatives be screened?
  • •Can you explain how my NT-proBNP levels have changed since my first day in the hospital, and what that tells us about my recovery?
  • •Beyond my Ejection Fraction, what was my Global Longitudinal Strain (GLS) score on my last echocardiogram?
  • •Have we ruled out all other potential causes for my heart failure, such as viral infections or pre-existing conditions, to confirm this is definitely PPCM?
  • •Is there a role for bromocriptine in my treatment plan to help block the 16kDa prolactin fragment?

Questions for You

3 questions

  • •Do I have a family history of heart failure, sudden cardiac death, or cardiomyopathy in my parents or siblings?
  • •What were the exact numbers (LVEF and BNP/NT-proBNP) on my most recent lab and imaging reports?
  • •Am I noticing a decrease in symptoms (like less shortness of breath) as my biomarker levels improve?

References

References (17)
  1. 1

    Peripartum cardiomyopathy: a review.

    Iorgoveanu C, Zaghloul A, Ashwath M

    Heart failure reviews 2021; (26(6)):1287-1296 doi:10.1007/s10741-020-10061-x.

    PMID: 34138401
  2. 2

    A contemporary review of peripartum cardiomyopathy.

    Patel PA, Roy A, Javid R, Dalton JA

    Clinical medicine (London, England) 2017; (17(4)):316-321 doi:10.7861/clinmedicine.17-4-316.

    PMID: 28765406
  3. 3

    Peripartum Cardiomyopathy: a Review for the Clinician.

    Khan A, Paré E, Shah S

    Current treatment options in cardiovascular medicine 2018; (20(11)):91 doi:10.1007/s11936-018-0690-3.

    PMID: 30269217
  4. 4

    Inhibition of the Notch1 pathway induces peripartum cardiomyopathy.

    Zhu RR, Chen Q, Liu ZB, et al.

    Journal of cellular and molecular medicine 2020; (24(14)):7907-7914 doi:10.1111/jcmm.15423.

    PMID: 32529705
  5. 5

    Titin-truncating variants are associated with heart failure events in patients with left ventricular non-compaction cardiomyopathy.

    Li S, Zhang C, Liu N, et al.

    Clinical cardiology 2019; (42(5)):530-535 doi:10.1002/clc.23172.

    PMID: 30851055
  6. 6

    TTN:c.12478del in proximal I-band of titin represents a common molecular cause of dilated cardiomyopathy in Slovenian patients.

    Vodnjov N, Cerar A, Maver A, et al.

    Orphanet journal of rare diseases 2025; (20(1)):92 doi:10.1186/s13023-025-03613-7.

    PMID: 40022161
  7. 7

    Truncated titin proteins in dilated cardiomyopathy.

    McAfee Q, Chen CY, Yang Y, et al.

    Science translational medicine 2021; (13(618)):eabd7287 doi:10.1126/scitranslmed.abd7287.

    PMID: 34731015
  8. 8

    Titin-truncating mutations in dilated cardiomyopathy: the long and short of it.

    Fatkin D, Huttner IG

    Current opinion in cardiology 2017; (32(3)):232-238 doi:10.1097/HCO.0000000000000382.

    PMID: 28151760
  9. 9

    The outcome of peripartum cardiomyopathy patients-single center experience.

    Demir E, Ceylan N, Bayraktaroğlu S, et al.

    Echocardiography (Mount Kisco, N.Y.) 2022; (39(12)):1608-1615 doi:10.1111/echo.15498.

    PMID: 36447302
  10. 10

    New Insights in Peripartum Cardiomyopathy.

    Cruz MO, Briller J, Hibbard JU

    Obstetrics and gynecology clinics of North America 2018; (45(2)):281-298 doi:10.1016/j.ogc.2018.02.002.

    PMID: 29747731
  11. 11

    Peripartum cardiomyopathy in the twenty-first century: a review of the pathophysiology and clinical trials for novel disease-specific therapeutics.

    Callender K, Briggs LA

    Heart failure reviews 2025; (30(2)):443-451 doi:10.1007/s10741-024-10475-x.

    PMID: 39671119
  12. 12

    Characterization of heart failure patients with reverse left ventricular remodelling post-angiotensin receptor blockers/neprilysin inhibitors therapy.

    Maizels L, Wasserstrum Y, Fishman B, et al.

    ESC heart failure 2022; (9(3)):1682-1688 doi:10.1002/ehf2.13801.

    PMID: 35178886
  13. 13

    The year in cardiovascular medicine 2020: heart failure and cardiomyopathies.

    Bueno H, Moura B, Lancellotti P, Bauersachs J

    European heart journal 2021; (42(6)):657-670 doi:10.1093/eurheartj/ehaa1061.

    PMID: 33388764
  14. 14

    Educational Recommendations on Selected Analytical and Clinical Aspects of Natriuretic Peptides with a Focus on Heart Failure: A Report from the IFCC Committee on Clinical Applications of Cardiac Bio-Markers.

    Kavsak PA, Lam CSP, Saenger AK, et al.

    Clinical chemistry 2019; (65(10)):1221-1227 doi:10.1373/clinchem.2019.306621.

    PMID: 31387884
  15. 15

    Universal definition and classification of heart failure: a report of the Heart Failure Society of America, Heart Failure Association of the European Society of Cardiology, Japanese Heart Failure Society and Writing Committee of the Universal Definition of Heart Failure: Endorsed by the Canadian Heart Failure Society, Heart Failure Association of India, Cardiac Society of Australia and New Zealand, and Chinese Heart Failure Association.

    Bozkurt B, Coats AJS, Tsutsui H, et al.

    European journal of heart failure 2021; (23(3)):352-380 doi:10.1002/ejhf.2115.

    PMID: 33605000
  16. 16

    Age-adjusted natriuretic peptide thresholds for a diagnosis of heart failure in the community: Diagnostic accuracy study.

    Taylor CJ, Taylor KS, Jones NR, et al.

    ESC heart failure 2025; (12(5)):3552-3568 doi:10.1002/ehf2.15383.

    PMID: 40717271
  17. 17

    BNP and NT-proBNP Interpretation in the Neprilysin Inhibitor Era.

    Sbolli M, deFilippi C

    Current cardiology reports 2020; (22(11)):150 doi:10.1007/s11886-020-01398-8.

    PMID: 32951154

This page provides educational information about the biology and diagnosis of peripartum cardiomyopathy (PPCM). It is not a substitute for professional medical advice from your cardiologist or obstetrician.

Get notified when new evidence is published on Peripartum cardiomyopathy.

We monitor PubMed for new peer-reviewed studies on this topic and email a short summary when something meaningful changes.