11:32am Monday 23 October 2017

Finding the cause, and the cure, for heart failure in new mothers

STORY: NATALIE SIMON

Professor Karen Sliwa’s first exposure to peripartum cardiomyopathy (PPCM) was in 1992, while she was training as a specialist physician at Chris Hani Baragwanath Hospital in Johannesburg. She noticed that the face of her daughter’s nanny, Othilia Mahlangu, was swollen every morning. She examined her, but beyond recognising that it was clearly a heart problem, Sliwa said she could not imagine what was ailing her. She took her to the cardiology clinic at Baragwanath where a cardiologist immediately diagnosed her with PPCM.

 

“I was quite surprised,” says Sliwa. “I had studied medicine for six years in Berlin, and had been working for quite a few years already, but had never heard of this disease.”

 
First studies to understand PPCM

 

While Sliwa herself had never heard of it, the South African medical community knew the disease well. That did not, however, translate into an understanding of what caused PPCM or how to treat it effectively. So years after this first exposure, when she was training as a cardiologist still working at Baragwanath Hospital, she decided to find out more about it.  First she simply observed 40 women who had developed the condition and described their health outcomes six months later. This research was published in a highly-respected journal because it was the first prospective single centre outcome study on PPCM using cardiac ultrasound.

 

Determined to study this disease more systematically, Sliwa collected blood samples from affected women.

 

“This was quite a challenge at the time because, back then, Baragwanath was not a hospital geared up for research. But I convinced somebody to give me money for a -80 degree freezer, which I squeezed into my tiny office to store my first samples.”

 

Unexpected challenges

 

After six months of work, Sliwa went away for a weekend. When she returned she discovered the freezer unplugged and all her samples destroyed. She had been unprepared for the annual spring-cleaning, which involved moving the freezer to vacumn underneath it.

Deciding she had to look for more creative solutions, she moved her -80 degree freezer into the middle of the cardiology clinic’s intensive care unit, and armed it with a really loud alarm that would go off if someone unplugged it.

 

“If somebody unplugged that fridge, all the patients in that ICU would become heart attack patients!  And the only way you could turn off that alarm was with a special code, which only I had.”

 
Finding the right collaborator and the missing link

 

Even with an alarm-protected freezer, Sliwa hit a number of of dead ends before she was put into contact with a biologist, Professor Denise Hilfiker-Kleiner, who had picked up in mice similar patterns seen in patients with PPCM. The two researchers met for coffee and got to speculating that perhaps the cause was related to breastfeeding, as the disease only manifested at the end of pregnancy and afterwards: the period in which the breastfeeding hormone prolactin is elevated.

 

They began to measure prolactin levels in the mice, and noticed the affected population had an abnormally high load of prolactin. These high levels appeared to cause major damage to the vessels in the heart. Studies on the human patients revealed the same thing.

 

Fortunately for Sliwa and Hilfiker-Kleiner, there already existed an inexpensive and safe drug that inhibits the ability to breastfeed, and thus the release of prolactin: a drug called bromocriptine. Studies on mice showed this drug to be effective, so the next natural step was to study its effect on humans.

 

“The challenge was that you cannot predict who will get this disease,” says Sliwa. They solved this by including a number of women who had developed peripartum cardiomyopathy with their first child, and were now pregnant with their second. The women were instructed to start taking the pill immediately after giving birth.

 

“The outcome, which was published in the journal Cell, was striking. The women who took the pill did not develop the condition in their second pregnancy.” says Sliwa.

 

They then designed a pilot study in which women who had developed the disease were randomly divided into two groups, one of which received the standard care for PPCM, while the other also received bromocriptine.

 

This study showed convincingly that taking bromocriptine in response to the onset of peripartum cardiomyopathy is extremely effective. The results of the pilot study have now been confirmed in a multi-centre prospective study, which is currently in press.  None of the patients receiving bromocriptine died or needed cardiac transplantation.

 

Download the publication here.

Despite this great advance in treating PPCM, it remains a disease that can only be picked up after birth, and too many women are diagnosed too late.

 

The way forward

 

Sliwa continues with the PPCM crusade.  Now director of the Hatter Institute of Cardiovascular Research, led from UCT, she is currently leading a global registry of the disease, which shows how prevalent it is not only in South Africa but also India, Germany, Pakistan, Australia and even the United Kingdom (UK). It is a truly global condition( Sliwa et al.2017)

“It seems to be more comon in black African and Mediteranean women, and less common in Caucasian women,” says Sliwa, “but we cannot be sure of this. A lot of cases are cropping up in the UK and Germany; it’s possible this disease is prevalent but has just been misdiagnosed.”

 

Read the publication.

She notes that even today, while the disease is well known in South Africa, it is still unknown in many other parts of the world. It’s therefore critical to create  awareness of this condition.

 
“Now that we know what it is and how to treat it, it is important that general practitioners and cardiologists all over the world know and understand the condition so they can pick it up and treat it immediately.”

 

 

Karen Sliwa was speaking at the June Café Scientifique event, hosted by UCT’s Research Contracts and Innovation (RC&I) office and funded by Spoor and Fisher. For more information about the Café Scientifique events contact Candice Jacobs.


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