Tag: cardiomyopathy

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ADHD Stimulants may Increase Risk of Cardiomyopathy in Young Adults, Study Finds

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Photo by Inzmam Khan

Young adults who were prescribed stimulant medications for attention-deficit/hyperactivity disorder (ADHD) were significantly more likely to develop cardiomyopathy compared with those who were not prescribed stimulants, in a study presented at the American College of Cardiology’s Annual Scientific Session.

The study found that people prescribed stimulants such as Adderall and Ritalin were 17% more likely to have cardiomyopathy at one year and 57% more likely to have cardiomyopathy at eight years compared with those who were not taking these medications. Cardiomyopathy involves structural changes in the heart muscle that weaken its pumping ability. It can cause a person to tire easily and limit their ability to perform daily tasks, and it often worsens over time.

However, researchers said that the overall risk of cardiomyopathy remained relatively low even when stimulants were used long-term. They said the findings do not necessarily point to a need for clinicians to change their approach to screening patients or prescribing stimulants.

“The longer you leave patients on these medications, the more likely they are to develop cardiomyopathy, but the risk of that is very low,” said Pauline Gerard, a second-year medical student at the University of Colorado School of Medicine in Aurora, Colorado, and the study’s lead author. “I don’t think this is a reason to stop prescribing these medications. There’s very little increased risk of these medications over the long term; it’s a real risk, but it’s small.”

ADHD is one of the most common neurodevelopmental disorders in children, affecting about 1 out of 10 American children aged 3 to 17, and can continue into adulthood. It is typically treated with behavioural therapy initially, which may be combined with stimulant or non-stimulant medications to help control behaviours that interfere with daily life and relationships. Stimulant medications can elevate blood pressure by causing the heart to beat faster and with greater force.

Most previous studies assessing the safety of stimulant medications have focused on the first year or two of use and found no evidence of harm to the heart. Since many patients are prescribed these medications in early childhood and continue taking them into adulthood, this new study was designed to assess their potential to cause harm over a longer period of time, Gerard said.

Using the TriNetX research database that includes information from about 80 hospitals across the U.S., researchers analysed data from people diagnosed with ADHD between 20–40 years of age. Individuals with the presence or absence of a prescription for stimulant medications along with rates of cardiomyopathy that could potentially be linked to stimulant use were included. Those with heart damage caused by other known factors, such as cancer treatments, were excluded.

For the analysis, the researchers paired each person who had been prescribed stimulants with an individual who had not been prescribed stimulants but was as similar as possible in all other respects, such as age, sex and other health conditions. Overall, 12 759 pairs were created and were followed for at least 10 years. Of these pairs, people prescribed stimulants were found to be significantly more likely to develop cardiomyopathy throughout the 10-year follow-up period, with the gap growing larger each year except the last two, when it narrowed slightly.

Despite the significant gap, the overall prevalence of cardiomyopathy was still quite low in both groups. After being prescribed stimulants for 10 years, 0.72% (less than three-quarters of one percent) of patients developed cardiomyopathy, compared with 0.53% (a little over half of one percent) among those who were not prescribed stimulants.

To put the numbers into context, Gerard said, “You can have almost 2000 patients on these medications for a year and you might only cause one of them to have a cardiomyopathy that they otherwise would not have had, but if you leave them on it for 10 years, 1 in 500 will have that happen.”

At these levels, researchers said the study does not suggest that aggressive testing for cardiovascular risk is warranted before prescribing stimulants, given that the potential benefits of testing must be balanced against the risks and costs. They suggest that further studies could help to identify subgroups of patients at greater risk who may benefit from future screening approaches.

Gerard said that it could also be helpful to study potential differences among different types of ADHD medications and different types of cardiomyopathies.

Source: American College of Cardiology

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In Diabetes, Oestrogen Protects Against Cardiomyopathy

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Oestrogen may protect diabetes patients from cardiomyopathy, according to research published in Circulation: Heart Failure. The study showed that severe insulin resistance in the heart causes cardiomyopathy and death in male mice, but also showed that oestrogen protected female mice.

“Cardiovascular disease is the major cause of morbidity and mortality for diabetic patients,” explained Shaodong Guo, PhD, primary investigator for the study at Texas A&M.

“Previous studies have shown that while there’s a lower instance of both cardiovascular disease and Type 2 diabetes in premenopausal women than in their age-matched male counterparts, these incidences rise sharply after female menopause,” Prof Guo said.

This indicates that the ovaries and ovarian hormones, such as oestrogen, may protect from Type 2 diabetes and cardiovascular diseases, he said.

The study investigated the role of ovaries and oestrogen in cardiac function and energy metabolism with mice who had the the cardiac insulin receptor substrate, IRS, modified or suppressed to mimic cardiac insulin resistance.

“Our previous studies reported that impaired cardiac insulin signalling with loss of insulin receptor substrate IRS1 and IRS2 genes leads to death of male mice,” he said. “In this study, we wanted to know how the removal of the ovaries might affect cardiomyopathy in female mice and also what other impacts the loss of insulin receptors might have on energy metabolism and mitochondrial function.” 

Insulin resistance and signaling

About 90–95% of patients with Type 2 diabetes suffer from insulin resistance, a risk factor for heart failure. In healthy tissue, insulin binds to insulin receptors, activating a network of intracellular signalling pathways. Disruptions in these signalling pathways have been linked to mitochondrial dysfunction, cardiomyopathy, and impaired glucose and fatty acid metabolism, among other health issues.

In this study, mice lacking IRS developed dilated cardiomyopathy, and analysis showed lowered activity of genes important for mitochondrial function and energy metabolism.

“Type 2 diabetes patients and insulin-resistant patients exhibit mitochondrial dysfunction,” Prof Guo explained.

The study fills in some blanks in understanding the role of insulin and estrogen signaling in mitochondrial function.

Study findings

Guo said there were four important findings from the study:

  • All female mice that lacked insulin receptor substrates survived for more than a year.
  • Female mice without insulin receptor substrates were less likely to experience severe cardiac dysfunction and death if they had ovaries. If the mice also lacked ovaries but received oestrogen, it prolonged their lifespans. Doses of oestrogen also protected IRS-altered male mice from heart dysfunction. 

Guo said oestrogen also prevents cardiomyopathy induced by loss of cardiac insulin receptor substrates.

“And removal of the ovaries leads to the death of female cardiac IRS1 and IRS2 double genes knockout mice if there is no reintroduction of oestrogen,” he said.

Loss of IRS1 and IRS2 genes in heart tissue disrupts cardiac energy metabolism, gene activity involved in mitochondrial function, and whole-body energy metabolism. However, oestrogen partially reverses these effects.

Oestrogen is important for healthy cellular signalling pathways and promotes mitochondrial function.

Prof Guo said the study shows that oestrogen enhances cardiac function, promotes energy metabolism, prevents cardiomyopathy and prolongs survival in both male and ovariectomy female mice lacking the insulin receptor substrates.  

“This study provides evidence for the gender difference for the incidence of cardiovascular disease and implies that oestrogen replacement therapy is feasible for the treatment of diabetic cardiomyopathy through enhancement of mitochondrial function and energy metabolism,” he said. “It also reveals some of the signalling pathways that may be potential therapeutic targets for the prevention or treatment of cardiovascular diseases in patients with Type 2 diabetes.” 

Guo also noted that diet could also play a role with oestrogens in foods.

“The study implies that food-derived oestrogens or phytoestrogens may play similar roles to oestrogen, as observed in mice,” he said. “This may help us reshape our knowledge of nutrient and food sciences related to plant hormones that can modulate chronic metabolic diseases such as Type 2 diabetes and associated cardiovascular complications.”

Source: Texas A&M University

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Mavacamten is Promising in Reducing Shortness of Breath in Cardiomyopathy

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Woman holding her chest
Photo by Joice Kelly on Unsplash

A new drug, mavacamten, shows promise in providing relief to cardiomyopathy patients experiencing shortness of breath, according to new research presented at the American College of Cardiology (ACC) Scientific Session.

Dr Florian Rader presented results of an international clinical trial showing that mavacamten alleviated the shortness of breath in patients with obstructive hypertrophic cardiomyopathy.

The genetic condition causes thickening of the heart muscle, and as a result, heart muscle cells enlarge and scarring often develops between cells. Patients with the condition typically experience shortness of breath, chest pressure, irregular heartbeat, and, although rare, sudden cardiac arrest.

“Until now, existing treatments for hypertrophic cardiomyopathy have been suboptimal, leaving most patients symptomatic and often, in need of invasive or even open-heart surgery,” said Dr Rader, who served as site principal investigator of the clinical trial at Cedars-Sinai Hospital. “Follow-up data from this extended clinical trial shows success in lessening the obstruction to blood flow out of the heart in hypertrophic cardiomyopathy. Along with this relief of obstruction came substantial improvements in symptoms and an important heart failure blood biomarker.”

As Dr Rader explained, mavacamten showed preliminary success in relieving symptoms associated with the condition – chiefly, shortness of breath, which can be debilitating.

Key data from the clinical trial includes:

  • The average age of the 231 clinical trial participants was 60 years old, and 39% of those on the trial were female. The median follow-up was 62 weeks.
  • 69% of trial participants had improved shortness of breath after 48 weeks of treatment.
  • Treatment with mavacamten was generally well tolerated, and no new safety concerns were raised during longer-term follow-up.

Dr Rader said that no disease-specific targeted treatment options have been developed for the condition since it was first described some 60 years ago.

Though the prevalence of hypertrophic cardiomyopathy is roughly 1 in every 200 patients, Dr Rader said that the condition is thought to be widely underdiagnosed.

“A lot of patients have the condition and often feel short of breath or palpitations but their doctor doesn’t recognise these symptoms as stemming from hypertrophic cardiomyopathy,” Dr Rader said. “Instead, patients may be told by their physician they are out of shape, need to lose weight or are suffering from an anxiety condition.”

The correct approach, said Dr Rader, is to first pay close attention to the patient’s symptoms. If shortness of breath is a main concern, then a doctor should listen to the patient’s heart for a murmur, then follow up with an electrocardiogram, and, ultimately, an echocardiogram, which most often will lead to the correct diagnosis.

Source: Cedars-Sinai Medical Center