Whitney J. Palmer

New research from a team at the Amsterdam University Medical Center suggests clinicians could use low-dose CT scans performed during lung cancer screenings to predict risk of cardiovascular mortality.

 investigators detailed how implementing a deep learning algorithm that is fueled with information captured during a low-dose CT exam for lung cancer screening can offer valuable details about calcification in the heart and the aorta.

Using LDCT in this way is a two-for-one opportunity to screen patients for both potentially deadly conditions. The scan is used to detect lung cancer in high-risk individuals, including heavy smokers, but for those individuals, cardiovascular disease actually surpasses lung cancer as the leading cause of death. By picking up these areas of calcification that are linked to plaque build-up, the scan can give providers a strong predictor of heart attacks, stroke, and mortality from cardiovascular disease.

Given the recent recommendation update from the U.S Preventive Services Task Force that opened up LDCT lung cancer screening to high-risk individuals ages 50-to-80 who have at least a 20-pack year smoking history, it is possible that providers will be able to pick up on cardiovascular disease mortality risk in an even wider population of patients, the team said.

In the past, data pulled from CT images has been used in conjunction with other risk factors, such as cholesterol levels, blood pressure, and self-reported history of illness. But, for this study, the team, led by Bob D. de Vos, Ph.D., from Amsterdam University Medical Center and the Image Sciences Institute at the University Medical Center Utrecht, drew upon deep learning to create an automated method that can quickly predict five-year cardiovascular disease mortality without putting a heavier work burden on providers.

“We have shown that five-year cardiovascular disease mortality can be predicted for lung screening participants in less than half a second, using only site-specific calcium scores automatically derived from lung screening low-dose CT,” the team said. “Hence, the proposed image-based analysis could aid in identification of lung screening participants at risk for cardiovascular disease mortality, without relying on self-reported participant data.”

Low-dose CT (LDCT) isn’t just for lung cancer screening. Data gathered from the scans can also help predict a patient’s five-year risk of death from cardiovascular disease.

 investigators from The Netherlands detailed how implementing a deep learning algorithm that is fueled with information captured during a low-dose CT exam for lung cancer screening can offer valuable details about calcification in the heart and the aorta.

For the study, they pulled data from LDCT scans conducted between August 2002 and April 2004 on 4,451 participants with an average age of 61 who were part of the National Lung Screening Trial. Using those details, the team trained their deep learning method to quantify six types of vascular calcification: thoracic aorta calcification (TAC), aortic and mitral valve calcification, coronary artery calcification (CAC) of the left main, the left anterior descending, and the right coronary artery. After training, they tested their method on data gleaned from 1,113 participants.

The team compared the methods with semi-automatic baseline prediction using self-reported participant characteristics, such as age, smoking history, and history of illness. According to their analysis, the prediction model using calcium scores performed better than the baseline model.

Specifically, the prediction model that used calcium scores reached a C statistic of 0.74 while the baseline model that relied on only participant characteristics achieved 0.69. The model had the best results, they said, when all variables were combined – a 0.76 C statistic.

“The analysis shows we found predictors that are typically not described in a literature, possibly because we performed analysis in lung cancer screening participants we are already at high risk of cardiovascular disease from a history of heaving smoking and the presence of extensive arterial calcification,” de Vos explained.

The method works in two stages, he said, first using deep learning to pinpoint the amount and location of arterial calcification in the coronary arteries and aorta. The second stage relies on a more conventional statistical approach to mortality prediction and identifies features that are most predictive of five-year mortality.

Incorporating the deep learning method into lung cancer screening would be simple, de Vos said, because it requires no special equipment and does not tack on any exam time. And, the benefits to providers and patients could be immense.

“The method uses only image information, it is fully automatic, and it is fast. The method obtains calcium scores in a complete chest CT in less than half a second. This means that the method should be easy to implement to routine patient work ups and screening,” he said. “Lung screening studies show that heavy smokers die from cardiovascular disease as much as from lung cancer. But, we also see that some people with very high calcium scores survive, while others with low scores do suffer from major cardiac events.”

Their results point to a need for additional research that can more specifically point to calcifications that are dangerous. To date, they have developed several automatic scoring methods that can use varied types of data, but they are continuing on with development. Now, de Vos said, they are concentrating on creating a calcium-scoring method that can use low-quality data, such as data affected by cardiac motion, low image resolution, and high noise level, to detect arterial calcification.

“We developed a method, for example, that can detect coronary calcification even when the lesions are below the clinically used threshold,” he said. “This way, we hope to increase the reproducibility of calcium scoring and enable more accurate prediction.”

But, for now, he said, their work has shown that it is possible to achieve real-time mortality prediction with lung screening chest CT by using only data from automatic deep learning-quantified arterial calcium.

This study, "

Deep Learning–Quantified Calcium Scores for Automatic Cardiovascular Mortality Prediction at Lung Screening Low-Dose CT

Articles

A deep-learning algorithm could help clinicians identify patients at increased risk of death from cardiovascular disease within the next 5 years based on the presence of vascular calcification. 

CT Scans from Lung Cancer Screenings Can Help Predict Risk of Cardiovascular Mortality

Conducting a contrast-enhanced cardiac MRI with a patient carries a very low risk of allergic reactions or other adverse events, but outcomes can vary based on various contrast agent characteristics, according to results of a new study.

In the study, investigators from the University Medical Center in Goettingen, Germany, focused on how a decision made by the European Medicines Agency (EMA) in 2017 affected patients undergoing this exam. Most contrast-enhanced cardiac MRIs use intravenous gadolinium-based contrast agents (GBCAs), and the EMA’s decision mandated the use of macrocyclic gadolinium contrast agent because it is less likely to accumulate in the body.

Typically, GBCAs are considered safe for this patient population, said the team led by Johannes Uhlig, MD, MPH, with adverse events being reported in 0.04 percent-to-2.2 percent of cases. But, there are questions around the impact of the likelihood that linear gadolinium will deposit in the body. In its decision, the EMA suspended linear gadolinium use except for liver imaging.

“Studies have demonstrated that the likelihood and extent of cerebral gadolinium depositions are increased after administration of linear GBCAs compared to macrocyclic GBCAs, although the clinical relevance of these depositions still needs to be determined,” he said.

To determine how the EMA decision affected the clinical impact of contrast-enhanced cardiac MRI, Uhlig’s team retrospectively reviewed MRI exams from 154,779 patients who were included in the European Society of Cardiovascular Radiology MRCT Registry from January 2013 to October 2019. Of the group, nearly 95 percent (145,855 patients) had a contrast-enhanced exam. Until 2017, 15.2 percent of exams used linear gadolinium, but that rate fell to less than 1 percent in 2018 and 2019.

Based on their analysis of patient outcomes, the team identified acute adverse events (AAEs) and classified them as mild, moderate, or severe. Overall, they discovered 556 AAEs among patients who had contrast-enhanced exams (0.38 percent), and only 47 were classified as severe or life-threatening. And, fewer AAEs were associated with macrocyclic GBCAs versus linear GBCAs (multivariable OR, 0.634, 95 percent CI: 0.452, 0.888, P=.008).

Among AAEs, the team said, allergic-like events were more common than physiologic ones, 71.58 percent and 28.42 percent, respectively, with the most common responses being wheezing and bronchospasms.

“Using a large-scale patient cohort from several European countries, our study demonstrates that the administration of GBCA for cardiac MRI is safe for the overwhelming majority of patients,” Uhlig said. “In particular, macrocyclic GBCAs exhibit a favorable acute safety profile, and should be considered for cardiac MRI examinations evaluating myocardial scarring, ischemia, cardiomyopathy, and myocarditis.”

But, GBCA administration was not responsible for all AAEs, he said. In fact, of the 8,924 cases that did not involve a contrast agent, there were 231 (2.59 percent) reported negative events. Most were related to anxiety and shortness of breath.

The team’s analysis also revealed more details about AAE incidence based on pharmacologic stressors, GBCA molecular structure, GBCA subtypes, and imaging indications, with the highest AAE incidence occurring in patients with known coronary artery disease. For instance, the team reported, patients who had stress cardiac MRIs were more likely to experience an AAE, and the highest rates occurred with the administration of dobutamine (1.78 percent) and regadenoson (1.26 percent). The lowest incidence appeared with the use of adenosine (0.53 percent). The longer half-life and different modes of action for regadenoson and dobutamine could be responsible for these differences, they said.

Additionally, the team also looked at outcomes based on GBCA subtypes. Overall, most AAEs occurred with patients who received gadoteridol (0.65 percent, 73 out of 11,161 patients). They also identified an increase among patients for whom a cardiac MRI was performed with gadobenate dimeglumine.

Ultimately, Uhlig’s team said, their findings point to the importance of pre-procedural assessments that can reveal any contraindications to MRI scanning and GBCA administration. Such an evaluation could provide insight into the likelihood of a GBCA-associated adverse event.

“Potentially vulnerable populations include those with orthostatic shortness of breath, prior adverse GBCA reactions, and terminal renal insufficiency,” Uhlig said.

Currently, there are no regulatory restriction on the use of linear GBCAs in the United States, but the U.S. Food & Drug Administration does advise providers to take gadolinium retention characteristics into consideration when selecting a GBCA for MRI scans.

Gadolinium-based Contrast Agents for Cardiac MRI: Use of Linear and Macrocyclic Agents with Associated Safety Profile from 154 779 European Patients

A recent study has found use of contrasting agents in cardiac MRIs carries a low risk for allergic reactions, vomiting, and other adverse events.

Low Risk of Adverse Events Associated with Cardiac MRI Contrast Agents 

A new study from investigators at the University of Texas Southwestern Medical Center is shedding new light on the clinical use of CT scans of calcified plaque for predicting 10-year heart attack and stroke risk.

Results of the study, which incorporated data from the Multi-Ethnic Study of Atherosclerosis and the Dallas Heart Study, indicate the coronary artery calcium (CAC) scores derived from the scans were better at predicting risk of heart attack than stroke.

“In our study, there was a two-fold greater risk of heart attack than stroke at CAC levels at or above 100,” said senior author Parag Joshi, MD, cardiologist and assistant professor of internal medicine. “That held true for black, white, and Hispanic men and women.”

These results, Joshi said, could help providers decide how aggressively to treat patients who have never have a major cardiac event, but who also have other risk factors, such as high blood pressure or high cholesterol.

The team’s findings were based on the evaluation of CT scans from 7,042 participants culled from the aforementioned studies. Based on those images, they divided the patients by the American Heart Association and American College of Cardiology’s calcium risk categories: 0, 1-99, and 100 and above. They also sub-divided the participants by sex and race in order to calculate the different risk levels.

Based on their analysis, the team found the risk for a heart attack was twice as high than a stroke for individuals with CAC scores greater than 100. For men in this group, the overall 10-year heart attack risk was 12 percent – slightly higher at 14 percent for Hispanic men – and it was 8 percent for women. Stroke risk in this group remained below 8 percent for all groups, but it was higher among women, black, and Hispanic participants.

For individuals in the 1-99 CAC score group, the risk for both heart attack and stroke hovered below 6 percent. But, women in this cohort had a greater stroke risk while men had a higher risk for heart attack. Among individuals with a 0 score, the 10-year risk for heart attack or stroke was less than 2 percent.

It is possible, Joshi’s team contended, that providers could use these findings from CT scans to inform their decisions about whether to place a patient on statin drugs when the choice is not clear-cut based on other factors, such as smoking history, blood pressure, or cholesterol.

“If you think your patient should be on a statin, and your patient does not want to take it, this can be a good arbitrator for that,” he said. “Our findings also highlight some of the nuance between heart attack risk and stroke risk and how our patients might consider those two risks in their decision making.”

This study is the first to compare the predictive value for heart attack and stroke risks. And, according to Leslee Shaw, PhD, professor of health services research in radiology in the Dalio Institute of Cardiovascular Imaging at Weill Cornell Medicine, the data is sufficiently robust to beneficial impact clinical care.

“The current report represents an important validation of prior prognostic results using CAC,” Shaw said in an accompanying 

. “The comparison of coronary heart disease versus stroke risk based on CAC findings adds novelty to this report and represents important information to enhance clinical decision making regarding asymptomatic screening for atherosclerotic cardiovascular disease.”

This study, “Predictive Value of Coronary Artery Calcium Score Categories for Coronary Events Versus Strokes: Impact of Sex and Race,” was published in 

Across racial and gender groups, CT scans that measure coronary artery calcium can more accurately predict the 10-year risk for heart attack.

CAC Scores Better for Predicting Heart Attack than Stroke

has increased substantially over the past 40 years in high-income countries, as has treatment and control of the condition. But, the level of control falls short of rates seen in dedicated hypertension programs, and it’s stagnating, according to research published last month in The Lancet.

This is the conclusion of an analysis conducted by Bin Zhou, Ph.D., of the Imperial College of London. His goal was to determine the prevalence of hypertension, the proportion of patients currently taking hypertension medication, and how well the condition is being managed.

“There has been substantial improvement in 

, treatment, and control in high-income countries since the 1980s and 1990s, most of which was achieved in the late 1990s and early 2000s,” Dr. Zhou and colleagues wrote. “Even in the best performing countries, the rates fall short of those achieved in high-quality hypertension programs, such as the Kaiser Permanente Northern California hypertension program. There is a need for strategies that further improve the diagnosis, treatment, and control of hypertension in high-income countries.”

According to study results, Canada, Germany, South Korea, and the United States have the highest rates of awareness, treatment, and control. Conversely, Finland, Ireland, Japan, and Spain have the lowest. Australia, Italy, New Zealand, and the United Kingdom were also included.

The study analyzed survey data collected from 526,335 individuals in 123 national health examination surveys from 12 high-income countries, focusing on individuals from ages 40-79. Patients were grouped by gender and 10-year age groups, and researchers focused on whether individuals were informed they had hypertension and whether they had been prescribed medication. They defined hypertension as systolic blood pressure of at least 140 mm/Hg, diastolic blood pressure of at least 90 mm/Hg, or being on prescribed hypertension medication.

Based on analyses, hypertension awareness rates began raising in the 1980s and continued through the late 1990s and early 2000s. The United States initially had the highest awareness rates with more than 50 percent in each age group and those levels have been largely maintained. Additionally, the United Kingdom and South Korea made significant improvements in awareness during the same time period. But, there has been very little improvement since then. The only increase in hypertension prevalence occurred with South Korean men and women ages 70-to-79.

Much of the augmentation in awareness, treatment, and control in high-performing countries can be attributed to increased use and compliance with clinical guidelines surrounding hypertension. Lowering the threshold for diagnosing and treating hypertension to 140/90 mm/Hg and improving identification of patients with stage 2 hypertension - systolic blood pressure at least 160 mm/Hg or diastolic blood pressure at least 100 mm/Hg - are largely responsible for progress. Newer, more effective drugs, such as renin-angiotensin system inhibitors and calcium-channel blockers, and fixed-dose therapies also facilitated treatment and helped many patients get the condition under control.

Countries with lower awareness, treatment, and control rates frequently recommend lifestyle changes as a first-line therapy effort, reserving medication as a later option. Additionally, some countries have a higher threshold for defining hypertension, so patients with 140/90 mm/Hg are less likely to receive intervention. Healthcare systems could also make it harder for patients to contact and communicate with their providers, making blood pressure checks less common.

Overall, the researchers say, these study results highlight the importance of incorporating and implementing clinical guidelines for hypertension. When these recommendations are in place, awareness, treatment, and control flourish.

There’s still a need for efforts that can continue to push hypertension management, they say. For example, more fixed-dose combination therapy can bolster control rates, and increasing contact with healthcare systems can increase diagnosis and treatment possibilities, particularly among population groups most at risk for hypertension.

NCD Risk Factor Collaboration (NCD-RisC). 

“Long-term and recent trends in hypertension awareness, treatment, and control in 12 high-income countries: an analysis of 123 nationally representative surveys.”

Published online July 18, 2019. http://dx.doi.org/10.1016/S0140-6736(19)31145-6

The rates for hypertension diagnosis, treatment and control are still falling short of goals despite awareness programs, researchers report.

Hypertension Awareness High in U.S., but Control Still Lags

Stimulating the sphenopalatine ganglion-a collection of nerve cells closely associated with the trigeminal nerve most responsible for headaches-could be a safe intervention for patients with acute ischemic stroke who aren’t eligible for thrombolytic therapy, according to an article published in 

Data analysis from two trials focused on 

, ImpACT-24A and ImpACT-24B, led by Jeffrey  Saver, M.D., director of the University of California at Los Angeles Comprehensive Stroke Center, reveals that acting on the sphenopalatine ganglion prompts arterial vasodilatation, significantly increasing blood flow to the brain and organs. Doing so could preserve the area immediately surrounding the stroke, as well as the blood-brain barrier to potentially reduce cerebral swelling and neurological outcomes.

“The sphenopalatine ganglion is the source of parasympathetic innervation to the anterior cerebral circulation,” the authors wrote. “We postulated that sphenopalatine ganglion stimulation might serve as a novel treatment approach for acute ischemic stroke by increasing blood flow to the ischemic area via enhancement of collateral circulation and by reducing cerebral edema.”

As a safe and effective therapy, it is also inexpensive, the authors wrote, indicting it could be a good therapeutic option for a wide array of frontline hospitals.

This randomized, double-blind, sham-controlled trial included 1,078 patients with anterior-circulation acute ischemic stroke from 73 medical center in 18 countries. These individuals were not undergoing reperfusion therapy, but they could begin treatment in the study within 8-to-24 hours post-stroke, a critical time for safeguarding neurological function. Roughly half of participants received active sphenopalatine ganglion stimulation treatment, and approximately half received a sham treatment. Their level of disability or improvement was evaluated after three months.

Patients in the intervention group underwent a minimally invasive procedure to implant a neurostimulator electrode in the pterygopalantine canal near the sphenopalatine ganglion. The control group received a puncture in the mucosa of the upper palate without neurostimulator implantation. Both groups underwent stimulation during 4-hour daily sessions for five consecutive days. On day 5, researchers conducted cerebral CT or MRI to determine infarct lesions size and potential hemorrhagic transformation before removing the neurostimulators. Follow-up visits were conducted at 30, 60, and 90 days.

At the end of the intervention period, 49 percent of patients in the sphenopalatine ganglion stimulation group improved beyond expectations as did 45 percent of the sham stimulation group. The therapy worked best for patients with no cortical involvement in their strokes. These individuals had fewer severe neurological deficients and fewer signs of stroke on imaging.

The clinical impact of these results could be significant, the authors wrote. The impact is nearly equivalent to the results of the existing therapy intravenous alteplase as a reperfusion therapy lasting less than three hours, and it outperforms intravenous alteplase in 3-to-4.5 hour therapies. The clinical benefit of sphenopalatine ganglion stimulation was even more significant when stimulation was at the low-to-midrange intensity.

Based on study results, the effects of sphenopalatine ganglion stimulation are the same no matter when the treatment is initiative during the first 24 hours after a stroke. Consequently, any patient treated during that time frame could reap the benefits, the authors wrote.

Further studies with more advanced imaging options might help determine the full extent of vessel occlusion, as well as safety and efficacy. Still, the authors wrote, the results are positive and could point to a new therapeutic option for stroke patients who can’t receive thrombolytic treatment.

“Although the improvement in 90-day functional outcome among patients with imaging evidence of cortical involvement at presentation was not significant in this trials alone, study findings indicate the use of sphenopalatine ganglion stimulation is likely to be beneficial,” the researchers wrote. “These findings provide support for the introduction into clinical practice of sphenopalatine ganglion stimulation for acute ischemic strong in patient with confirmed cortical involvement.”

Bornstein N, Saver J, Diener H, et. al., "

An injectable implant to stimulate the sphenopalatine ganglion for treatment of acute ischaemic stroke up to 24 h from onset (ImpACT-24B): an international, randomized, double-blind, sham-controlled, pivotal trial

," The Lancet (2019), doi: 10.1016/S0140-6736(19)31192-4.

Stimulating the sphenopalatine ganglion-a collection of nerve cells closely associated with the trigeminal nerve most responsible for headaches-could be a safe intervention for patients with acute ischemic stroke who aren’t eligible for thrombolytic therapy, according to an article published in The Lancet last month.

Stimulation Therapy Safe for Some Acute Ischemic Stroke Patients

Fewer heart disease-related deaths occur in counties where Medicaid was expanded under the Affordable Care Act (ACA), according to new research.

 at the American Heart Association’s Quality of Care Outcomes Research Scientific Sessions 2019, counties with more widely available Medicaid, as of 2016, experienced a small, but significantly lower cardiovascular mortality rate.

The largest benefit occurred in nonmetropolitan, high-poverty areas.

Heart disease and its risk factors are more prevalent among uninsured individuals. Consequently, Sameed Ahmed M. Khatana, MD, a cardiovascular disease fellow at the Hospital of the University of Pennsylvania, analyzed whether Medicaid expansion had a meaningful impact on middle-aged adults. This is one of the first large studies with that goal.

“We believe these findings will be helpful for policy makers and health policy researchers in trying to tease out the impact of this most recent round of expansion,” he said.

To determine the effect, researchers examined county-level, age-adjusted cardiovascular mortality rates collected from the Centers for Disease Control and Prevention Wide-Ranging Online Data for Epidemiological Research morality database. They included all individuals aged 45 to 64 years from 2010 to 2016. Adults from Massachusetts and Wisconsin were excluded, however, as Medicaid expansion in those states was non-ACA related.

Investigators included data from 1,960 counties in 29 states and Washington, DC. Based on results, expansion counties had greater health insurance coverage for low-income individuals than non-expansion counties [19.8% (SD=5.5) vs 13.5% (SD=3.9); p<.01].

While there were no significant differences observed in mortality rate trends before Medicaid expansion, the widened coverage produced a shift. Expansion counties experienced a significantly smaller cardiovascular mortality rate increase [141.9 (95% CI 135.6, 148.3) to 142.0 (95% CI 135.5, 148.6) deaths per 100 000 residents annually] than non-expansion counties [176.1 (95% CI 169.3, 182.8) to 180.6 (95% CI 173.2, 188.0) deaths per 100 000 residents annually].

After accounting for demographic differences and economic variables, researchers determined that, post-expansion, expansion counties had 4.0 (95% CI 2.1, 6.0) fewer cardiovascular-disease deaths per 100 000 residents annually than non-expansion counties.

Ultimately, Khatana said, results show Medicaid expansion could beneficially affect cardiovascular mortality.

“We can't necessarily say from our study that giving a person health insurance through Medicaid will save their life,” he said. “However, our study does show that there, perhaps, were at least widespread benefits concentrated in certain groups, such as those uninsured or people with higher risk of cardiovascular disease, although we can’t say for sure it was a direct result of the Medicaid expansion.”

Still, he added, states deliberating Medicaid expansion should consider the cardiovascular benefit in this population.

Association of Medicaid expansion with cardiovascular mortality-a quasi-experimental analysis.

 Circ Cardiovasc Qual Outcomes. (2019), doi: 10.1161/hcq.12.suppl_1.3

Fewer heart disease-related deaths occur in counties where Medicaid was expanded under the Affordable Care Act, according to a provocative new study.