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Q&A With Ming Hui Chen, MD: Changes In Diastolic Function After HSCT In Children
Although changes in systolic function over time after hematopoietic stem cell transplantation (HSCT) have been well documented, echocardiographic data on the rate of changes in diastolic function prior to the development of clinically overt disease is lacking in post-HSCT patients, including children.1
The Bottom LineMing Hui Chen, MD, MMSc and colleagues, in a previous study conducted at the Boston Children's Hospital/Dana-Farber Cancer Institute, demonstrated subclinical declines in systolic and diastolic function among children at 1-year post HSCT and suggested that these changes could become clinically significant with time.2
Within a longer-term follow-up study, Dr. Chen and her fellow researchers continued to assess these children to track the rate of change in diastolic function over multiple time points. They sought to determine if diastolic decline found in the short-term progressed even further or improved over time.1
Their subsequent analysis, published online ahead of print in Transplantation and Cellular Therapy, included patients who were younger than 21 years at the time of HSCT (2005-2008) and who had a baseline echocardiogram (pre-HSCT) and annual surveillance echocardiograms post HSCT (2006-2020). Sixty-one patients were followed for a median of 7.4 years; 41% were female; median age at HSCT was 10.7 years; and median number of echocardiograms per patient was 8.1
MedPage Today interviewed Dr. Chen about the findings revealed in the longer-term study, including those for projected declines in heart function, and the value of these observations in cardiac care for HSCT patients. Dr. Chen serves as Director of the Cardiovascular Health for Cancer Survivors Program, the C-BrDG (Cardiac-Brain Development and Genetics) Program, and the Stress Echocardiography Program at Boston Children's Hospital and as Associate Professor of Medicine, Harvard Medical School, Boston, MA.
The interview was lightly edited.
MedPage Today: What did your results reveal about the decline in diastolic function indices post-HSCT? On the basis of linear projections, diastolic function was estimated to become abnormal how many years post HSCT?
Dr. Chen: Over a median follow-up time of 7.4 years, we found that left ventricular (LV) and right ventricular diastolic function indices appear to exhibit a linear pattern of decline. Our findings suggest that 50% of this pediatric HSCT population will have abnormal diastolic indices within 12 to 25 years post-HSCT if the observed trends continue.
Importantly, these projections use age-adjusted Z-scores to characterize diastolic dysfunction, because indices of normal diastolic function change in children as a function of age. (The Z-score measures how far from the mean/median a data point deviates; more precisely, it represents how many standard deviations above or below the age and gender mean the patient's data point lies.) Our use of Z-scores allowed us to compare indices of diastolic function as children grow in this pediatric population.
What did your study uncover about the decline in systolic function post-HSCT? Systolic function was estimated to become abnormal how many years post HSCT?
After HSCT, systolic function declined more slowly than diastolic function in this population, with the population mean LV ejection fraction (LVEF) Z-score projected to be abnormal 40 years post-HSCT. While this timeframe may seem remote, it is important to highlight that it corresponds with middle age for a young HSCT patient.
How did TBI and anthracycline exposure contribute to the decline in heart function?
TBI-exposed patients had lower indices of LV diastolic function and lower LVEF Z-scores than non-exposed patients. Additionally, in a subset of patients with adequate post-HSCT images of the entire left atrium, left atrium reservoir and left atrium conduit strain values were lower in TBI-exposed versus unexposed HSCT patients.
In contrast, anthracycline exposure was not related to a significant decline in diastolic indices in our study, though it was associated with declining LVEF. Notably, the median anthracycline exposure in our study was 150 mg/m2, which is lower than the amount typically associated with high cardiotoxic risk.
As an isolated risk factor, anthracycline exposure did not appear to change the risk of diastolic dysfunction that was associated with TBI. However, because over half of the participants in our study were exposed to both therapies, we had limited sample sizes for a subgroup analysis, which challenges our ability to refine risk of diastolic dysfunction with TBI or anthracycline exposure independent of each other.
Still, the finding that anthracycline exposure was associated with a decline in LVEF over the long-term supports prior studies suggesting that there is no completely safe anthracycline dose.
What do you think underlies the rate of decline post HSCT being greater for diastolic function than for systolic function?
There are likely many pathophysiological factors underlying this finding. For example, radiation to the chest, which occurs with TBI, is known to cause microvascular damage that leads to heart muscle fibrosis and stiffening of the heart muscle or diastolic dysfunction, often with preserved LVEF or the ability to pump out blood.
Other studies also suggest that metabolic syndrome involving high blood sugar levels, elevations in body weight, and high blood pressure is associated with abnormal diastolic function, but not with abnormal LVEF in childhood cancer survivors. Subclinical myocardial injury without reduced LVEF likely occurs among HSCT survivors, which can be detectable with non-invasive measures of diastolic function.
On the basis of your findings, what should clinicians keep in mind for the cardiac care of HSCT survivors?
Clinicians should adhere to current guidelines for echocardiographic screening in survivors of childhood cancer, which take into consideration TBI and anthracycline exposure. Careful clinical follow-up and screening for heart failure symptoms is warranted. Consideration of longitudinal screening of biomarkers in the blood, such as BNP [B-type natriuretic peptide] or NT-proBNP [N-terminal proBNP], may be helpful.
Our findings may help patients and clinicians better understand the trajectory of diastolic function over time and may also inform a lifespan perspective on disease management as HSCT survivors transition from pediatric to adult care.
Our study findings underscore that it's not the systolic function, but the diastolic function that first becomes abnormal in these patients. The projected time course of diastolic and systolic dysfunction may be helpful for clinicians in tailoring their care for higher-risk patients.
Knowing the trends in diastolic and systolic dysfunction will help with the continuity in surveillance among adult survivors of pediatric HSCT, as they transition healthcare providers. Our findings may encourage clinicians and patients to be vigilant in adhering to surveillance guidelines for young populations, which can help facilitate timely intervention and inform best practices for long-term cardiac care for survivors.
Published: October 12, 2023
Gloria Arminio Berlinski, MS, has been working as a freelance medical writer/editor for over 25 years and contributes regularly to MedPage Today.
Low Diastolic Blood Pressure: What Causes It And What You Can Do
You may develop low diastolic blood pressure due to certain medications or aging. You can also have low diastolic blood pressure if you have low blood pressure overall.
The medical term for low blood pressure is hypotension. If you have hypotension, your systolic pressure measurement is under 90 millimeters of mercury (mm Hg) and your diastolic number is under 60 mm Hg.
Some people can have low diastolic pressure even when their systolic pressure is considered normal. This condition is called isolated diastolic hypotension.
Unlike the rest of your body, which receives blood when your heart pumps, the muscles of your heart receive blood when your heart relaxes.
If your diastolic blood pressure is too low, your heart muscles won't get enough oxygenated blood. This can lead to the weakening of your heart, a condition called diastolic heart failure.
You may have low diastolic blood pressure if you take specific medications or due to aging. You can also have low diastolic blood pressure if you have low blood pressure in general (hypotension). Treatment for low diastolic blood pressure largely depends on the type of hypotension.
Isolated diastolic hypotensionThere are a few known causes of isolated diastolic hypotension.
MedicationsAlpha-blocker medications are blood pressure medications that work by causing your blood vessels to open up, or dilate. Because they lower diastolic pressure more than systolic pressure, they may cause isolated diastolic hypotension.
Common brand names include prazosin (Minipress) and doxazosin (Cardura).
If you're taking an alpha-blocker and have low diastolic blood pressure, a doctor can prescribe a different high blood pressure medication.
AgingAs we age, we lose the elasticity of our arteries. For some older adults, the arteries may become too stiff to spring back between heartbeats, causing low diastolic blood pressure.
If you have isolated low diastolic pressure and you're not on blood pressure medication, the only option may be to see your doctor more frequently for checkups and to watch for symptoms of heart failure.
Currently, there's no medication available to treat isolated diastolic hypotension.
Overall low blood pressureThere are several common causes of overall hypotension, which would include a low diastolic number. Treatment of general hypotension depends on the cause.
MedicationsFor some people, especially people over age 60, lowering systolic blood pressure below 120 with medication may cause diastolic pressure to fall below 60. This is considered overtreatment of high blood pressure.
Overtreatment of high blood pressure can be managed by adjusting or changing medications. The goal is to keep the diastolic blood pressure between 60 and 90 mm Hg.
Many medications besides those for blood pressure can cause hypotension. They include:
A doctor may also change other medications that cause hypotension.
Heart conditionsSome heart problems can cause hypotension. These can include:
If you have one of these medical conditions, treating it may help raise your blood pressure to normal levels.
DehydrationDehydration can also cause hypotension.
If you don't take in enough fluids, your blood pressure can become dangerously low. This may happen if you're taking a diuretic and lose more fluids than you take in.
Dehydration can be treated with fluid replacement. In some cases, you may need medications that increase blood pressure.
Other causesSome people may experience low blood pressure due to:
Symptoms of isolated diastolic hypotension include:
Because low diastolic pressure decreases blood flow to your heart, you may also have chest pain (angina) or symptoms of heart failure, including:
Medical emergency
Call 911 and go to the nearest emergency room if you have chest pain or difficulty breathing.
Symptoms of hypotensionIf you have low diastolic blood pressure along with low systolic blood pressure (hypotension), you may experience additional symptoms. Symptoms of hypotension include:
You may need medical attention if you have any of these symptoms.
Low diastolic blood pressure doesn't always lead to a larger health concern. But in some cases, the effects of low diastolic blood pressure may be long lasting and potentially life threatening.
Complications of low diastolic blood pressure include:
Risk of injury from fallsIf your blood pressure is low enough, it can cause symptoms such as fainting or dizziness.
This causes a significant risk of falling. This can lead to serious injuries, such as head trauma.
Heart tissue damage and heart diseaseResearchers have found a link between low diastolic blood pressure and heart damage.
A 2020 study found that low diastolic blood pressure and some cardiac issues, such as stroke, heart attack, and heart failure, may have a correlation.
A 2023 study suggests that health conditions such as diabetes that may cause initial high blood pressure can ultimately cause low diastolic blood pressure. This is because the inflammation causes vascular injury and the blood vessel walls become damaged due to high blood pressure. This damage can lead to heart failure.
Some things you can do to help prevent and manage low diastolic pressure may include:
Low diastolic blood pressure is 60 mm Hg or lower. If your blood pressure is 90/60 mm Hg or lower, doctors consider you to have low blood pressure.
What causes a low diastolic pressure?Low diastolic blood pressure tends to occur as a result of taking medication for high blood pressure. It may also happen due to aging and other medical conditions.
How do you treat low diastolic blood pressure?If you have low diastolic blood pressure and take an alpha-blocker, doctors may switch your blood pressure medication to another one.
What heart problems cause low diastolic blood pressure?People with certain heart conditions may be more likely to develop low blood pressure (low systolic and low diastolic blood pressure). These can include heart valve problems, heart failure, and a slow heart rate (bradycardia).
Hypotension can be dangerous because it's a frequent cause of falls. Isolated diastolic hypotension can decrease blood flow to your heart. Over time, isolated diastolic hypotension can potentially lead to heart failure.
Pay attention to your diastolic number when you have your blood pressure checked. If your lower number is 60 mm Hg or below, ask a healthcare professional about it.
Let a doctor know if you have any symptoms of hypotension or heart failure. In many cases, switching medications along with making lifestyle changes can help. A doctor may want to follow you more closely to ensure your diastolic pressure stays above 60 mm Hg.
Hormones And High Blood Pressure: Study Reveals Endocrine Culprits And Targeted Treatments
In a recent study published in Hypertension Research, scientists examine the endocrine causes of hypertension (HTN) and investigate the efficacy of treatments to alleviate HTN.
Study: Endocrine causes of hypertension: Literature review and practical approach. Image Credit: Hodoimg / Shutterstock.Com
About 30% of the global population is affected by HTN. HTN is a modifiable cardiovascular (CV) risk factor that is associated with a significant number of deaths worldwide.
There are two types of HTN known as primary and secondary HTN. As compared to primary HTN, secondary HTN causes greater morbidity and mortality.
The most common endocrine causes of HTN include primary aldosteronism (PA), paragangliomas and pheochromocytomas (PGL), Cushing's syndrome (CS), and acromegaly. Other causes include congenital adrenal hyperplasia, mineralocorticoid excess, cortisol resistance, Liddle syndrome, Gordon syndrome, and thyroid and parathyroid dysfunction.
What is PA?PA is the most common endocrine cause of hypertension, which is associated with excessive aldosterone secretion by the adrenal gland and low renin secretion. It is difficult to estimate the true prevalence of PA due to the complexity of its diagnosis.
Typically, the plasma aldosterone-to-renin ratio (ARR) is measured to diagnose PA. The diagnosis of PA can also be confirmed using other diagnostic tools like chemiluminescent enzyme immunoassays (CLEIAs) and radio immune assay (RIA).
Continuous aldosterone secretion is associated with organ damage due to chronic activation of the mineralocorticoid (MR) receptor in many organs, including fibroblasts and cardiomyocytes. An elevated level of aldosterone causes diastolic dysfunction, endothelial dysfunction, left ventricular hypertrophy, and arterial stiffness.
Increased aldosterone secretion also leads to obstructive sleep apnea and increases the risk of osteoporosis. This is why individuals with PA are at a higher risk of cardiovascular events (CVDs), including heart failure, myocardial infarction, coronary artery disease, and atrial fibrillation.
PA is treated by focusing on normalizing potassium and optimizing HTN and aldosterone secretion. Unilateral adrenalectomy is a surgical procedure proposed to treat PA.
Young patients who are willing to stop medication are recommended surgical treatment. The most common pharmaceutical treatment for PA includes mineralocorticoid receptor antagonists such as spironolactone and eplerenone.
Pheochromocytomas and paragangliomasPGL are tumors that develop at the thoracic-abdominal-pelvic sympathetic ganglia, which are present along the spine, as well as in the parasympathetic ganglia located at the base of the skull. The incidence rate of PGL is about 0.6 for every 100,000 individuals each year. PGL tumors synthesize excessive catecholamines (CTN), which induce HTN.
Some of the common symptoms linked to HTN associated with PGL are palpitations, sweating, and headache. PGL can be diagnosed by determining metanephrines (MN) levels, which are degraded products of CTN. Bio-imaging tools also play an important role in confirming the diagnosis of PGL.
Excessive secretion of CTN increases the risk of CVDs, including Takotsubo adrenergic heart disease, ventricular or supraventricular rhythm disorders, hypertrophic obstructive or ischaemic cardiomyopathy, myocarditis, and hemorrhagic stroke. Excessive CTN secretion also causes left ventricular systolic and diastolic dysfunction.
Typically, PGL treatment is associated with surgical procedures. Two weeks before the surgery, patients are treated with alpha-blockers. For these patients, beta-blockers are not used as the first line of treatment without prior use of alpha-adrenergic receptors.
Patients with high CTN secretion are treated with metyrosine, as this can inhibit tyrosine hydroxylase. Hydroxylase converts tyrosine into dihydroxyphenylalanine, which is related to CTN synthesis.
What is CS?CS, which arises due to persistent exposure to glucocorticoids, is a rare disease with an incidence rate of one in five million individuals each year. The most common symptoms of CS include weight gain, purple stretch marks, muscle weakness, acne, and hirsutism. A high cortisol level causes cardiovascular complications such as HTN, hypercholesterolemia, and diabetes.
CS is diagnosed based on the presence of two or more biomarkers that can be identified through pathological tests, such as salivary nocturnal cortisol, 24-hour urinary-free cortisol, and dexamethasone suppression tests.
CS is treated through surgical procedures based on the detected lesions. Patients with severe CS are treated with steroidogenic inhibitors, such as metyrapone, ketoconazole, osilodrostat, and mitotane. Pituitary radiotherapy and bilateral adrenalectomy are performed when other treatments are not effective.
AcromegalyAcromegaly arises due to chronic exposure to growth hormone (GH), leading to excessive insulin-like growth factor 1 (IGF1) synthesis. This condition has a relatively higher incidence rate of 3.8 million person-years. Clinical symptoms of acromegaly include thickened lips, widened nose, a rectangular face, prominent cheekbones, soft tissue overgrowth, or skeletal deformities.
Prolonged exposure to GH leads to increased water and sodium retention, insulin resistance, reduced glucose uptake, and increased systemic vascular resistance. These conditions increase the risk of HTN and diabetes in patients with acromegaly. Acromegalic patients are also at a higher risk of cancer, particularly those affecting the thyroid and colon.
Acromegaly is diagnosed using the IGF1 assay, which determines IGF1 levels in serum. After confirming the presence of high IGF1 levels, a GH suppression test must be performed to confirm the diagnosis. Bioimaging is also conducted to locate adenoma.
Acromegaly is commonly treated through surgical procedures. Patients who refuse this line of treatment are treated with somatostatin receptor ligands, growth hormone receptor antagonists, dopaminergic agonists, or radiotherapy.
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