AMPK deficiency in smooth muscles causes persistent pulmonary hypertension of the new-born and premature death

Study Proposes New Heart Failure Treatment Targeting Abnormal Hormone Activity

Duke-NUS scientists and their collaborators have discovered a potential new treatment for heart failure with preserved ejection fraction (HFpEF), a type of heart disease that is notoriously difficult to treat. The team discovered that the diseased heart cells had high levels of glucagon activity, a pancreatic hormone that raises blood sugar (glucose) levels. Armed with this novel insight, the scientists demonstrated that a drug that blocks the hormone's activity, can significantly improve heart function.

In heart failure, which is considered a global pandemic, the heart can no longer pump blood effectively. In Singapore, heart failure is a leading cause of death, accounting for 17 percent of cardiac admissions locally. Globally, an estimated 64 million people live with this condition, with HFpEF accounting for around half of the cases.

In HFpEF, the heart can pump normally but its muscles are too stiff to relax to re-fill the chambers with blood properly. It is often seen in older adults and people with multiple risk factors including high blood pressure (hypertension), obesity and diabetes. They typically have symptoms such as shortness of breath, fatigue and reduced ability to exercise. This is unlike heart failure with reduced ejection fraction (HFrEF), where the heart muscle is weakened and unable to pump with enough force—therefore, less blood is being pushed into the body.

There have been studies on how the heart is stressed by hypertension and metabolic diseases associated with obesity, such as diabetes, but these have been done in isolation of each other. This latest study, which was published in Circulation Research, addresses this gap by taking into account both stressors, revealing for the first time, the molecular pathway that contributes to HFpEF progression.

In pre-clinical studies, the team of scientists, which included collaborators from the University of Cincinnati College of Medicine, University of California Los Angeles, University of Toronto and University of North Carolina School of Medicine, investigated how stress from hypertension affected lean hearts versus diabetic/obese ones.

In their findings, the lean models developed heart failure with reduced ejection fraction (HFrEF), typically observed in hypertensive patients. The obese models, however, developed heart failure with preserved ejection fraction (HFpEF), proving that a combination of stressors give rise to the disease and providing a good model for further studies.

Using advanced single-cell RNA-sequencing technologies, the scientists were then able to study the expression of every detected gene in every single heart cell, allowing them to uncover specific genetic variations in cells associated with HFpEF. The scientists found that in the obese models, the most active genes were the ones driving the activity of glucagon.

Professor Wang Yibin, Director of the Cardiovascular & Metabolic Disorders Program at Duke-NUS and senior author of the study, said, "Under stress conditions such as high blood pressure and metabolic disorders like obesity and diabetes, we found that glucagon signaling becomes excessively active in heart cells. This heightened activity contributes to the development of heart failure with preserved ejection fraction (HFpEF) by increasing heart stiffness and impairing its ability to relax and fill with blood."

The team then tested a drug that blocks the glucagon receptor in a pre-clinical model of HFpEF and found significant improvements in heart function, including reduced heart stiffness, enhanced relaxation, improved blood filling capacity and overall better heart performance.

Assistant Professor Chen Gao from the Department of Pharmacology, Physiology and Neurobiology at the University of Cincinnati College of Medicine; and the study's first author, said, "Our study shows strong evidence that a glucagon receptor blocker could work well to treat HFpEF. Repurposing this drug, which is already being tested in clinical trials for diabetes, could bypass the lengthy drug development process and provide quicker and more effective relief to millions of heart patients."

Professor Patrick Tan, Senior Vice-Dean for Research at Duke-NUS, commented, "With our aging population, there will likely be more patients with multiple conditions, including heart failure, diabetes and hypertension, presenting a significant challenge to health systems. Uncovering the synergistic impact of such illnesses and their underlying mechanisms is key to better understanding the complex process of heart failure and developing an effective treatment for the disease."

The researchers hope to work with clinical partners to conduct clinical trials to test the glucagon receptor blocker in humans with HFpEF. If these succeed, it could become one of the first effective treatments for this challenging condition, significantly improving the quality of life for millions worldwide.

More information: Chen Gao et al, Glucagon Receptor Antagonist for Heart Failure With Preserved Ejection Fraction, Circulation Research (2024). DOI: 10.1161/CIRCRESAHA.124.324706

Citation: Study proposes new heart failure treatment targeting abnormal hormone activity (2024, September 30) retrieved 1 October 2024 from https://medicalxpress.Com/news/2024-09-heart-failure-treatment-abnormal-hormone.Html

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Heart: Understanding Atrial Fibrillation Causes, Symptoms, And Management

In some instances, medical procedures are necessary

Atrial fibrillation (AFib), the most common heart arrhythmia, affects millions globally. It's marked by an irregular, often rapid heartbeat and can lead to serious complications like stroke, heart failure, and other heart issues. Understanding its causes, recognizing symptoms, and knowing management options are vital for those living with AFib.

What is Atrial Fibrillation?

Atrial fibrillation (AFib) occurs when the heart's upper chambers (atria) beat irregularly and out of sync with the lower chambers (ventricles), disrupting normal blood flow. This increases the risk of blood clots forming in the atria, which can travel to the brain and cause a stroke. AFib can be intermittent, with episodes that come and go, or persistent, requiring treatment to restore a normal heart rhythm.

Causes of Atrial Fibrillation

AFib can result from a variety of factors, and often, multiple factors contribute to its development. Some of the most common causes include:

1. High Blood Pressure: Hypertension is one of the leading causes of AFib. High blood pressure forces the heart to work harder, which can lead to structural changes in the heart and the development of AFib.

2. Heart Disease: Conditions such as coronary artery disease, heart valve problems, and congenital heart defects can increase the risk of AFib. Scarring from a previous heart attack can also contribute.

3. Thyroid Disorders: Both an overactive thyroid (hyperthyroidism) and an underactive thyroid (hypothyroidism) can lead to AFib.

4. Age: The risk of AFib increases with age, particularly after the age of 60.

5. Lifestyle Factors: Obesity, excessive alcohol consumption, smoking, and high levels of stress can all contribute to the development of AFib.

6. Sleep Apnea: This condition is characterised by repeated interruptions in breathing during sleep, and is a significant risk factor for AFib.

7. Genetics: A family history of AFib increases the likelihood of developing the condition.

Symptoms of Atrial Fibrillation

AFib can present with a wide range of symptoms, varying from person to person. Some individuals may experience significant discomfort, while others might have no symptoms at all. The most common symptoms include:

Palpitations: A fluttering, pounding, or racing sensation in the chest is one of the hallmark signs of AFib.

Fatigue: Feeling unusually tired, even with minimal exertion, is a common symptom due to the heart's reduced efficiency.

Shortness of Breath: Difficulty breathing, especially during physical activity or when lying down, can be a symptom of AFib.

Dizziness or Lightheadedness: An irregular heartbeat can lead to reduced blood flow to the brain, causing dizziness or fainting spells.

Chest Pain: Some people with AFib may experience chest discomfort or pain, which should always be evaluated by a doctor to rule out a heart attack.

Weakness: Generalised weakness or a feeling of being unwell can also indicate AFib.

Management of Atrial Fibrillation

Managing Atrial Fibrillation (AFib) requires a multifaceted approach involving lifestyle changes, medications, and medical procedures to control the heart's rhythm and reduce stroke risk. Medications are central to AFib management, with rate control drugs like beta-blockers and calcium channel blockers used to slow the heart rate and ease symptoms. Antiarrhythmic medications may also be prescribed to maintain a normal heart rhythm, particularly in persistent AFib cases. To reduce stroke risk, blood-thinning medications (anticoagulants) are often recommended to prevent blood clots from forming in the atria.

Lifestyle modifications play a crucial role in managing AFib. A heart-healthy diet rich in fruits, vegetables, whole grains, and lean proteins supports heart health, while regular, doctor-approved exercise can improve cardiovascular fitness and lessen AFib symptoms. Maintaining a healthy weight is also important, as it can lower the likelihood of AFib episodes. Additionally, reducing alcohol and caffeine intake helps avoid potential AFib triggers, and stress management techniques such as yoga, meditation, and deep breathing can be effective in controlling stress, which is known to trigger AFib.

In some instances, medical procedures are necessary. Cardioversion, which uses electrical shocks or medications to reset the heart's rhythm, can be effective in certain cases. Catheter ablation, where a catheter is inserted to destroy small areas of heart tissue causing the abnormal rhythm, is another option. In more severe cases, a pacemaker might be implanted to help regulate the heart's rhythm.

When to Seek Medical Attention

If you experience symptoms of AFib, such as palpitations, chest pain, or shortness of breath, it's important to seek medical attention promptly. Early diagnosis and treatment can significantly reduce the risk of complications, including stroke and heart failure.

Conclusion

Atrial fibrillation is a serious condition that requires careful management, but with the right treatment and lifestyle changes, individuals with AFib can lead full, active lives. Understanding the causes, recognizing the symptoms, and following a comprehensive management plan are key to effectively controlling this common heart arrhythmia.

Content by: Dr. Aparna Jaswal, Director of Cardiology at Fortis Escorts Heart Institute & Research Centre, New Delhi Disclaimer: The opinions expressed within this article are the personal opinions of the author. NDTV is not responsible for the accuracy, completeness, suitability, or validity of any information in this article. All information is provided on an as-is basis. The information, facts, or opinions appearing in the article do not reflect the views of NDTV and NDTV does not assume any responsibility or liability for the same.

World Heart Day: Warning Signs Of A Weak Heart

The heart is an extremely resilient organ. It has a high capacity to compensate and tolerate insults, in most cases. And therein lies the problem. A heart which gradually becomes weaker and weaker may be so well compensated that we may not have any symptoms at all, no warning signs, no hints that something is amiss….The heart is essentially a pump, propelling blood to all the parts of the body. When the heart cannot perform this function, the blood backs up and fluid fills into the lungs much like a sponge soaked after dipping it in water! This happens due to the heart being unable to pump blood forward (systolic heart failure) or being so stiff that it cannot receive blood properly (diastolic heart failure).Warning signs of heart failure can develop gradually or all of a sudden when the heart goes beyond its tipping point. Supplying blood to the whole body is no meagre task. When the heart is weakening one of the commonest symptoms is simply, fatigue! Tiredness, inability to do tasks which were comfortably done before, weakness, these complaints are often disregarded, neglected and ignored.The most important symptom is shortness of breath which occurs due to the fluid build up in the lungs, ever so often starting while doing exertional activities and often progressing to breathlessness at rest. The biggest red flag for clinicians is a symptom called orthopnea which in simple terms is breathlessness on lying down flat. Patients get up at night while lying down, with a choking sensation, have to takes gasps of air (air hunger) and feel comfortable just sitting up. They spend the night sitting on a chair or bent over on a table. Never ignore this symptom ! Other kinds of breathlessness include being breathless after bending down (bendopnea). Often signs of 'wet lungs' are a dry irritating cough, worse on lying down and better when sitting up. Sometimes, relatives will hear an audible wheeze when the patient breathes. This can be confused for asthma or allergies but can also come from the heart.As the fluid build up worsens, patients experience swelling of the feet and ankles, inadvertent weight gain, feeling a fullness in the abdomen, loss of appetite and nausea. Patients also may experience rapid or irregular heart beats, an in ability to exercise and even spells of fainting. In later stages, patients experience a dullness and lack of concentration and an inability to carry of routine daily tasks without discomfort. May of the readers will be wondering, what about chest pain? Chest pain, the biggest warning of heart problems, have I forgotten to mention this in my long account of warning signs? Unless the patient has experienced a heart attack which then causes sudden heart weakness and heart failure, chest pain is noteworthy by its absence.

Sitting too long raises risk of heart disease and cancer

Identification of heart failure or cardiac congestion is by doing basic tests like electrocardiogram, echocardiogram, chest x-ray and blood work especially tests called NT pro-BNP as well as advanced tests like cardiac MRIs. The treatment is centred around finding and treating the cause like heart attacks, high blood pressure, heart rhythm disturbances, cardiomyopathies and other systemic diseases. The treatment involves 'drying out' the lungs with urine forming medicines called diuretics and in the long run, strengthening the heart with medicines like beta blockers and RAAS inhibitors.The heart is an extremely resilient organ. Even when it is weak, with the correct cardiac rehabilitation, exercise and nutrition planning and support of medications, it can bounce back. Several patients with weak hearts can have a normal functional and exercise capacity and live a comfortable 'normal' life.(Author: Dr. Nihar Mehta, Associate Director, Structural Heart Department, Jaslok Hospital and Research Centre)

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