Category: Cardiovascular Disease

Categories : Cardiovascular DiseaseTags :

Recurrence Risk of Heart Attack is Increased by Long Hours

On By ModernMedia
Photo of neon-lit heart by Leon Collett, via Unsplash.

For heart attack survivors, the risk of recurrent coronary heart disease is increased by working long hours.

Heart attack survivors who working 55+ hours per week were at higher risk of recurrent coronary heart disease (CHD) events (ie, myocardial infarction [MI] or unstable angina) over 6 years compared with people working a more standard 35-40 hours a week (adjusted HR 1.67). This included adjustment for sociodemographics, lifestyle-related risk factors, clinical risk factors, work environment factors, and personality factors.

“These results showed a linear risk increase after 40 h/week and a stronger effect after the first 4 years of follow-up and when long working hours are combined with job strain,” wrote Xavier Trudel, PhD, of CHU de Québec-Laval University Research Centre in Quebec City, and colleagues. 
The researchers suggested secondary interventions in curbing working hours among patients at risk of CHD recurrence.

In an accompanying editorial, Jian Li, MD, PhD, of UCLA, and Johannes Siegrist, PhD, of Heinrich-Heine-University, concurred: A “short standardized assessment of working time and stressful working conditions among economically active cardiac patients would enrich physicians’ awareness of patients’ needs and inform medical decision making.”

“With the transformation of the modern work due to technological advances and economic globalisation, an increase in work load and an extension of irregular, nonstandard forms of employment, including working from home, were reported, aggravating the control and prevention of long working hours,” Drs Li and Siegrist wrote.

They urged cardiac rehabilitation programmes to offer “training skills of coping with stressful demands and of strengthening resilience and relaxation” and involving occupational health services to develop return-to-work plans.

When cardiac disease patients return to work, their workplaces will need to adopt tailored, programs to retain the workers and manage disease, Drs Li and Siegrist added.

The prospective cohort study included 967 MI survivors under age 60, of whom 205 had a recurrent CHD event over follow-up averaging 5.9 years.Men and people in their 40s and 50s were most likely to be working long hours after an MI. Job strain, defined as a combination of high psychological demands and low decision latitude at work, was measured with a questionnaire.

Work hours for each participant were assessed only once, at about 6 weeks after returning to work. “Some patients could have changed exposure during follow-up, leading to potential nondifferential misclassification and to an underestimation of the true effect,” Trudel’s group acknowledged.

The observational study was limited by only one tenth of participants being women, limiting generalisability, and by unknown confounding variables.

“In conclusion, the study by Trudel et al. provides a new piece of research evidence that work-related factors play an important role in CHD prognosis,” Drs Li and Siegrist wrote. “Occupational health services are urgently needed to be incorporated into cardiac rehabilitation programs and secondary prevention of CHD.”

Source: MedPage Today

Journal article information: Trudel X, et al “Long working hours and risk of recurrent coronary events” J Am Coll Cardiol 2021; DOI: 10.1016/j.jacc.2021.02.012.

Editorial information: Li J, Siegrist J “Occupational risks of recurrent coronary heart disease” J Am Coll Cardiol 2021; DOI: 10.1016/j.jacc.2021.02.020.

Categories : Cardiovascular DiseaseTags :

Genetic Clues to ‘Silent Strokes’ Uncovered

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After years of research, scientists have uncovered genetic clues to ‘silent strokes’, a major cause of vascular dementia, opening up new pathways to prevention and treatment.

Lacunar strokes are caused by the weakening of the walls of small blood vessels in the brain that can be only a millimetre in diameter. Such strokes by these can often happen in a stepwise progression, only to be detected when symptoms are noticeable and damage has been done. Few drugs are available to prevent or treat these kinds of strokes.  

Thus far, only one genetic fault has been linked to lacunar strokes. Professor Hugh Markus, BHF-funded researcher and neurologist at the University of Cambridge led a study working with researchers around the world to investigate the genetics behind lacunar strokes. They believe their breakthrough can yield treatments for lacunar stroke and vascular dementia.

Recruiting participants from around the world after they attended hospital and had an MRI or CT brain scan., the researchers scanned and compared the genetic code of 7338 patients who had a lacunar stroke with 254 798 people who had not. They found 12 genetic regions associated with lacunar strokes

The researchers found that these 12 genetic regions are linked to vascular control, and dysfunctions make the blood-brain barrier more permeable to toxins, and messages sent around the brain slow down or fail to arrive completely.

“These small and often silent lacunar strokes have gone under the radar for a long time, and so we haven’t been able treat patients as well as we’d like to,” said study leader Prof Hugh Markus. “Although small, their consequences for patients can be enormous. They cause a quarter of all strokes and they are the type of stroke which is most likely to lead to vascular dementia.

“We now plan to use this new genetic blueprint as a springboard to develop much needed treatments to prevent lacunar strokes from occurring in the first place and to help stave off dementia.”

First author Dr Matthew Traylor, of the study at Queen Mary University of London, said: “Genetics offers one of the few ways we can discover completely new insights into what causes a disease such as lacunar stroke. It is only by better understanding of what causes the disease that we will be able to develop better treatments.”

Professor Sir Nilesh Samani, Medical Director at the British Heart Foundation and cardiologist, said: “This is the most extensive genetic search to date which truly gets to grips with what cause lacunar strokes. These findings are a significant leap forward and we now have a much greater understanding of the genetics and biology behind what causes the small blood vessels deep in the brain to become diseased.

“Lacunar strokes affect around 35 000 people in the UK each year. This research provides real hope that we can prevent and treat this devastating type of stroke much better in the future.”

Source: Medical Xpress

Journal information: The Lancet Neurology (2021). DOI: 10.1016/S1474-4422(21)00031-4

Categories : Cardiovascular Disease GenderTags :

Cardiovascular Diseases in Transgender Youth

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Young transgender people face a higher risk of cardiovascular diseases, according to a new study.

Anna Valentine, MD, of the University of Colorado Anschutz Medical Campus in Aurora, presented the findings of her team’s study at the Endocrine Society’s virtual ENDO 2021 meeting. Existing research shows increased cardiovascular risks in adult transgender people.

Researchers found that transgender youths assigned female at birth had a higher risk of obesity compared to cisgender female youths, as well as a nearly doubled chance of polycystic ovary syndrome. However, transgender youth did not have an increased risk of hypertension, dysglycaemia, or liver dysfunction.

These differences could be explained by any number of different mechanisms, Dr Valentine explained. “We know that some youth with gender dysphoria have higher rates of overweight and obesity, and that having overweight and obesity itself increases your risk of having other diagnoses.” It is also known that “youth with gender dysphoria have higher rates of mental health comorbidities … as well as getting less physical activity,” she said.

“And they also may be taking medication that could all influence their cardiometabolic health,” she added.

Adult transwomen taking estradiol are more likely to have higher levels of triglycerides and a higher rate of stroke, blood clots, and myocardial infarction (MI). Adult trans men are at greater risk of elevated triglycerides, low-density lipoprotein cholesterol, and body mass index (BMI), as well as lower high-density lipoprotein cholesterol, and an increased risk of MI.
The data of 4174 paediatric patients (average age of 16) diagnosed with gender dysphoria, were compared with 16 651 cisgender controls. This data came from six large paediatric centres. Participants were matched with four controls.

However, the data did not include information on which participants were receiving hormonal treatment, which is something that Dr Valentine is looking to address in her research.

“We do know that in the adult data, that there is some association with estradiol use and testosterone use with differences in cholesterol parameters, but this is still an emerging field in paediatrics,” Dr Valentine explained. “We have some small single-center studies that sometimes say ‘yes, with hormones we see an increase in BMI,’ but other studies say ‘this section looks very stable on this hormone’.”

“The fact that we have such a large cohort in this multicentre analysis for our next steps, I think it will be really interesting to look at that,” she added.

Source: MedPage Today

Presentation information: Valentine A, et al “Multicenter analysis of cardiometabolic-related diagnoses in transgender adolescents” ENDO 2021.

Categories : Cardiovascular DiseaseTags :

Patients Might Benefit From Thrombectomy in Basilar Strokes

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Despite the disappointing results of the BEST and BASICS trials for basilar artery occlusion strokes, in some cases, patients might benefit from endovascular therapy (EVT) after all, according to a closer look at the data.

Raul Nogueira, MD, of Grady Memorial Hospital and Emory University School of Medicine in Atlanta, and colleagues in the VERITAS group, presented their findings at the American Stroke Association virtual International Stroke Conference.

On adjusted intention-to-treat analysis, among the 351 stroke patients with baseline NIH Stroke Scale (NIHSS) scores of ≥ 10, having EVT showed a 38.7% chance of zero-to-moderate disability modified Rankin Scale [mRS] 0-3) at 90 days compared to 26.5% with best medical management (adjusted OR 1.94).

EVT also offered a mortality reduction benefit over controls (40.3% vs 48.2%), although at the risk of increased risk of symptomatic intracranial hemorrhage (5.0% vs 0.6%). Subgroup analysis suggested that older patients tended to have especially good outcomes with EVT.

Based on the study’s results, it does appear “that some patients with basilar artery occlusion strokes benefit from mechanical thrombectomy,” commented Steven Hetts, MD, of UCSF Mission Bay Hospitals in San Francisco.

“The trends do appear to be toward favoring EVT in selected patients, which is consistent with our earlier experience in anterior circulation large vessel occlusion [LVO] strokes,” he noted.

Given how rare they are, posterior circulation LVO strokes are challenging to study, and are also characterised by complex symptoms and severity.

Nogueira noted that the BEST and BASICS were underpowered as they had suffered from poor recruitment, crossovers, and selection issues. Additionally, the BASICS trial had undergone a protocol modification to allow recruitment of people with milder strokes (NIHSS <10), which had potentially diluted the treatment effect. An important point which had been missed was that underlying atrial fibrillation was more prevalent at baseline among the EVT arm than controls.

This implies “that their basilar occlusions may more likely have been from embolization of a clot from the heart to an otherwise normal basilar artery,” according to Dr Hetts. “I would expect that those patients would do better clinically than patients with underlying atherosclerotic disease in the basilar artery itself that leads to basilar artery occlusion.”

Source: MedPage Today

Presentation information: Nogueira RG, et al “Vertebrobasilar occlusion randomization to endovascular reperfusion versus intravenous thrombolysis or medical treatment alone systematic evaluation (VERITAS) collaboration” ISC 2021; Abstract LB 11.

Categories : Cardiovascular Disease Medical Research & TechnologyTags :

New Smart Speakers That Can Remotely Monitor Heartbeat

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Smart speaker services like Amazon’s Alexa have shown that they can be adapted to monitor the breathing of babies, and recent development has enabled them to detect heartbeats without contacting the skin.

“Heart rhythm disorders are actually more common than some other well-known heart conditions. Cardiac arrhythmias can cause major morbidities such as strokes, but can be highly unpredictable in occurrence, and thus difficult to diagnose,” explained co-senior author Dr Arun Sridhar, assistant professor of cardiology at the UW School of Medicine. “Availability of a low-cost test that can be performed frequently and at the convenience of home can be a game-changer for certain patients in terms of early diagnosis and management.”

Instead of listening to the heartbeat, the smart speaker emits a continuous sound which bounces off the patient’s body. Changes in the received sound are associated with motions in the body from a heartbeat.
“The motion from someone’s breathing is orders of magnitude larger on the chest wall than the motion from heartbeats, so that poses a pretty big challenge,” said lead author Anran Wang, a doctoral student in the Allen School. “And the breathing signal is not regular so it’s hard to simply filter it out. Using the fact that smart speakers have multiple microphones, we designed a new beam-forming algorithm to help the speakers find heartbeats.”

Beam-forming is a technology where an array of emitters or receivers can change the direction in which a signal is emitted or received. Applications of such technology include directing sound only in one direction, such as a person watching TV while another wants quiet while they read,
Much in the way AI systems sort out sounds to identify human speech, the algorithm developed by the team can pick up heartbeats. As this does not produce the usual peaks seen in heartbeat monitors, this also requires processing the heartbeat further to extract the inter-beat interval.
“With this method, we are not getting the electric signal of the heart contracting. Instead we’re seeing the vibrations on the skin when the heart beats,” Mr Wang said.

The researchers tested their prototype smart speaker system on 26 healthy participants and 24 patients with hospitalised with a variety of cardiac conditions. The team compared the smart speaker’s inter-beat interval with one from a standard heartbeat monitor. Of the nearly  2,300 heartbeats measured for the healthy participants, the smart speaker’s median inter-beat interval was within 28 milliseconds of the standard monitor. With cardiac patients, the median inter-beat interval measured by the smart speaker was within 30 milliseconds of the standard.

The technology is currently set up for spot checks; a person concerned about their heart rhythm could sit in front of a smart speaker for a reading. In the future, the researchers hope that the system could be set up to monitor heartbeats for long periods, such as when they are sleeping, helping to diagnose conditions like sleep apnoea.

Source: Medical Xpress

Categories : Cardiovascular DiseaseTags :

Central Retinal Artery Occlusion Needs to be Treated as A Stroke

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The American Heart Association published a new scientific statement, “Management of Central Retinal Artery Occlusion,” which laid out the best methods to treat what is effectively a small stroke in the eye.

A central retinal artery occlusion (CRAO) is a rare (1 in 100 000 people) form of acute ischaemic stroke arising from a blockage of blood flow to the main artery of the eye. It causes painless, immediate vision loss in the impacted eye from which less than 20% of people will recover from.

“Central retinal artery occlusion is a cardiovascular problem disguised as an eye problem. It is less common than stroke affecting the brain but is a critical sign of ill health and requires immediate medical attention,” said the chair of the statement writing committee Brian C Mac Grory, MBBCh, BAO, MRCP, an assistant professor of neurology and staff neurologist at the Duke Comprehensive Stroke Center at Duke University School of Medicine. “Unfortunately, a CRAO is a warning sign of other vascular issues, so ongoing follow-up is critical to prevent a future stroke or heart attack.”

In a comprehensive review of the literature, committee members from a variety of specialties summarised the state of the science in this condition. They noted that a lack of clinical trials results in physicians not recognising the problem, including that it is a type of stroke, resulting in inaction and differing methods of diagnosis and treatment.

“We know acute CRAO is a medical emergency requiring early recognition and triage to emergency medical treatment,” said Dr Mac Grory. “There is a narrow time window for effective treatment of CRAO and a high rate of serious related illness. So, if a person is diagnosed in a doctor’s office or another outpatient clinic, they should be immediately sent to a hospital emergency department for further evaluation and treatment.”

CRAOs can be caused by problems with carotid arteries, the blood vessels in the neck, but there is also evidence CRAOs could be caused by heart problems such as atrial fibrillation.

CRAO risk factors include age and the presence of cardiovascular risk factors such as type 2 diabetes, smoking, and obesity. 

Currently, the literature suggests that intravenous tissue plasminogen activator (tPA) treatment, a “clot buster” also used for brain strokes, could be effective. However, to be effective and safe tPA must be administered within 4.5 hours of the onset of symptoms

Hyperbaric oxygen and intra-arterial alteplase, were also noted as showing potential but requiring further study. Hyperbaric oxygen can result in an improvement if done within 24 hours of the CRAO event. Other possible treatments needing further research icnclude breaking up clots with novel thrombolytics and using novel neuroprotectants (substances capable of preserving brain function and structure) in concert with other treatments to restore blood flow in the blocked artery.

Since there is potential for future strokes or even heart attacks, patients should undergo screening and treatment of vascular risk factors as a matter of urgency. CRAOs are complex to treat and manage, requiring the joint effort of a team of specialists.

Secondary prevention (including monitoring for complications) must be a collaborative effort between neurologists, ophthalmologists, cardiologists and primary care clinicians. Risk factor modification includes lifestyle and pharmacological interventions.

Source: News-Medical.Net

Journal information: Grory, B. M., et al. (2021) Management of Central Retinal Artery Occlusion: A Scientific Statement From the American Heart Association. Stroke. doi.org/10.1161/STR.0000000000000366.

Categories : Cardiovascular Disease COVIDTags :

Study Shows That COVID Causes Heart Damage

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Heart problems in COVID are caused by the virus invading heart cells and causing damage, according to a new study.

Heart problems such as arrhythmia and lack of pumping ability were associated with COVID even at the start of the pandemic. However, it was not clear whether these effects were caused by the virus, or whether it was due to the body’s inflammatory response in mounting a defence against the virus. 

“Early on in the pandemic, we had evidence that this coronavirus can cause heart failure or cardiac injury in generally healthy people, which was alarming to the cardiology community,” said senior author Kory J Lavine, MD, PhD, an associate professor of medicine. “Even some college athletes who had been cleared to go back to competitive athletics after COVID-19 infection later showed scarring in the heart. There has been debate over whether this is due to direct infection of the heart or due to a systemic inflammatory response that occurs because of the lung infection.”

Dr Lavine, along with other researchers from the Washington University School of Medicine, engineered stem-cell derived tissue as a model for how human heart tissue contracts. Studying these heart tissue models, they came to the conclusion that the viral infection kills muscle cells as well as the muscle fibre units involved in heart muscle contraction. This cell death and muscle fibre destruction happened even without inflammation.

“Our study is unique because it definitively shows that, in patients with COVID-19 who developed heart failure, the virus infects the heart, specifically heart muscle cells,”  Dr Lavine said. “Inflammation can be a second hit on top of the damage caused by the virus, but the inflammation itself is not the initial cause of the heart injury.”

While other viral infections have been linked to heart damage, SARS-CoV-2 is unique in that monocytes and dendritic cells dominate the immune response, while other viruses that damage the heart attract T and B cells.

“COVID-19 is causing a different immune response in the heart compared with other viruses, and we don’t know what that means yet,” Dr Lavine said. “In general, the immune cells seen responding to other viruses tend to be associated with a relatively short disease that resolves with supportive care. But the immune cells we see in COVID-19 heart patients tend to be associated with a chronic condition that can have long-term consequences. These are associations, so we will need more research to understand what is happening.”

Source: News-Medical.Net

Journal information: Bailey, A. L., et al. (2021) SARS-CoV-2 Infects Human Engineered Heart Tissues and Models COVID-19 Myocarditis. JACC: Basic to Translational Science. doi.org/10.1016/j.jacbts.2021.01.002.

Categories : Cardiovascular DiseaseTags :

Only Smaller ‘Good’ Cholesterol Particles Reduce Heart Risk

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New research on cholesterol shows that ‘good cholesterol’ is not all good for the heart – only smaller particles reduce heart risk.

Higher levels of ‘good cholesterol’ or high-density lipoprotein cholesterol (HDL-c ) have been associated with better cardiovascular outcomes. In contrast, ‘bad cholesterol’ or low-density lipoprotein cholesterol (LDL-c ), deposits cholesterol on artery walls, increasing the risk of cardiovascular disease.

Medications that lowers LDL-c  also reduce cardiovascular risk, but medication that increases HDL-c does not decrease cardiovascular risk. This paradox calls into question the assumption that HDL-c is protective against cardiovascular risk.

Researchers analysed the size of HDL-c particles, which is determined by genetic characteristics, and compared this to the risk of myocardial infarction. The results showed that genetic characteristics for having large HDL-c particles were associated with increased heart attack risk. Characteristics for smaller HDL-c particles were linked to reduced heart attack risk.

“There is a positive causal relationship between the size of HDL cholesterol particles and the risk of heart attack, so although we have to increase the levels of good cholesterol in the blood, they must always be small particles,” explains the study’s principal investigator, Dr Robert Elosua, a researcher at the Hospital del Mar-IMIM, CIBERCV, and the University of Vic-Central University of Catalonia.

The HDL-c particles are more effective in transferring cholesterol to the liver for subsequent elimination. “If we need to do something in relation to HDL, it is to increase the number of small particles, which are those that adequately perform the function of eliminating cholesterol, those that really move it to the liver for removal, and do not allow it to accumulate in the arteries and cause cardiovascular disease,” said Dr Álvaro Hernáez.
There are currently no drugs that increase HDL-c and also reduce cardiovascular risk. “This study highlights new and potential therapeutic targets in the field of cardiovascular diseases, including several genes related to the qualitative aspects of HDL particles, which may contribute to cardiovascular prevention,” concluded first author Dr Albert Prats.

Source: Medical Xpress

Journal information: Albert Prats-Uribe et al, High-density lipoprotein characteristics and coronary artery disease: a Mendelian randomization study, Metabolism (2020). DOI: 10.1016/j.metabol.2020.154351

Categories : Cardiovascular Disease Diet and NutritionTags :

High GI Carbohydrates Raise CVD Risk Across Countries

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A multinational study has shown that high consumption of high glycaemic index foods increases the risk of cardiovascular disease (CVD) events such as stroke or heart disease, regardless of pre-existing CVD.

The study examined low-, middle- and high-income countries, beginning in 2006, with a median follow-up of 9.5 years. Data was used from nearly 120 000 participants.

The glycaemic index was first introduced in the 1970s to compare the rise of blood glucose from a given carbohydrate food in a patient in comparison to their blood glucose curve from the same patient ingesting glucose. This ranges from 20 for fructose to 100 for barley. In comparison to individuals eating low glycaemic index foods, those eating high glycaemic index foods had a greater risk of CVD events (51%) if there was pre-existing CVD, and even without CVD (21%). 

The highest glycaemic index foods were eaten in China, followed by Africa and Southeast Asia. The highest glycaemic loads were seen in Southeast Asia, followed by Africa and China. Glycaemic load is a better measure of a food’s effect on blood sugar taking into account how quickly it enters the bloodstream and how much glucose can be delivered.

There was less of an effect seen with glycaemic load only those with preexisting CVD showed an association between high glycaemic load diets and patient outcomes.

The participants were given a questionnaire, breaking foods down into seven categories based on glycaemic load and frequency, with a number of options each.

The broad geographic and economic scope of this study enabled the investigation of glycaemic index and load across a wide range of diets that would not be possible if it were restricted to sampling only Western-style diets.

“As expected, a higher glycaemic index was associated with an increased risk of adverse effects among the participants with a higher BMI, as reported previously,” the researchers wrote. “Although the glycaemic index of foods is independent of glucose-tolerance status, the overall postprandial glycaemic response to diet increases as the BMI increases.”

The authors acknowledge that economic development may have altered the mix of diets sampled over time, leading to an overestimation of glycaemic foods in China, for example. The findings nonetheless have important implications for primary and secondary prevention of CVD.

Source: MedPage Today

Journal information: Jenkins DJA, et al “Glycemic index, glycemic load, and cardiovascular disease and mortality” N Engl J Med 2021; DOI: 10.1056/NEJMoa2007123.

Categories : Ageing Cardiovascular Disease Substance UseTags :

Recreational Substances Including Cannabis Linked to Heart Disease

On By ModernMedia

Alcohol, tobacco and cannabis are among recreational drugs that contribute to early-onset atherosclerotic cardiovascular disease (ASCVD) in young people, a study has found.

The study drew on data of more than a million people receiving primary care services throughout the VA Healthcare System in 2014 or 2015, of whom there were 135 703 with premature ASCVD.

A number of independent predictors for first-event ASCVD for men (from age 55) and women (from 65) were picked up. Tobacco (adjusted odds ratio [OR] 1.97) and alcohol use (OR 1.50)  conferred significant additional risk, but the greatest risk increase of generally legal substances was cannabis use (OR 2.65). Cocaine use (OR 2.44), amphetamine use (OR 2.74) and other drug use (OR 2.53) all had very high risk increases.

Those using four or more substances had the greatest risk at nearly nine times normal. Women also had much stronger effect sizes for premature ASCVD than men.

In an accompanying editorial Anthony Wayne Orr, PhD, and colleagues at LSU Health Shreveport, wrote: “Substance use disorders have been associated with an acceleration of the ageing process. We are only young once, and we should do everything in our power to maintain that state as long as we can.”

The editorialists suggested a nationwide ASCVD education campaign targeting people with substance use disorders.

“In addition, clinicians and primary care providers should begin screening their adult and young adult patients with a history of a substance use disorder for symptoms of premature or extremely premature ASCVDs at earlier stages in their patients’ lives,” suggested the editorialists.

Limitations included it being an observational study, lack of socioeconomic data and the cohort being mostly white males, as well as not being able to discern between prescription and recreational amphetamine use.
“Retrospective studies are limited by the available data. While this study supports the association between substance use disorder and early-onset ASCVD, the effect of substance use frequency, dose, and duration cannot be reliably ascertained in this patient sample,” the editorialists stated.

The editorialists recommended that specific biomarkers for substance use-associated cardiovascular disease be identified, and therapeutic window characterised to limit these chronic effects of substance use disorder.

Source: MedPage Today

Journal information: Mahtta D, et al “Recreational substance use among patients with premature atherosclerotic cardiovascular disease” Heart 2021; DOI: 10.1136/heartjnl-2020-318119.

Editorial information: Scott ML, et al “Young at heart? Drugs of abuse cause early-onset cardiovascular disease in the young” Heart 2021; DOI: 10.1136/heartjnl-2020-318856.