Tag: arrhythmia

Categories : Cardiovascular DiseaseTags :

Research at Oktoberfest Reveals a Brewing Cardiac Arrhythmia Risk

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Medicine is subjecting the negative effects of alcohol on body and health to ever greater scrutiny – not surprisingly us, as alcohol is one of the strongest cell toxins that exist. In a recent study, doctors at  took mobile ECG monitors along to parties of young people who had one principal aim: to drink and be merry. Yet the science produced by the MunichBREW II study made for sobering reading. It revealed that binge drinking can have a concerning effect on the hearts even of healthy young people in surprisingly many cases, including the development of clinically relevant arrhythmias. The results of the study have just been published in the European Heart Journal.

The team from the Department of Cardiology at LMU University Hospital launched the MunichBREW I study at Munich Oktoberfest in 2015. Back then, the doctors, led by Professor Stefan Brunner and PD Dr Moritz Sinner, studied the connection between excessive alcohol consumption and cardiac arrhythmias – but only through an electrocardiogram (ECG) snapshot.

Now the scientists wanted to gain a more detailed picture, so they set out with their mobile equipment once again. Their destinations were various small parties attended by young adults with a high likelihood “that many of the partygoers would reach breath alcohol concentrations (BAC) of at least 1.2 grams per kilogram,” says Stefan Brunner. These were the participants of the MunichBREW II study – the world’s largest investigation to date of acute alcohol consumption and ECG changes in prolonged ECGs spanning several days.

Hearts out of sync – especially in recovery phase

Overall, the researchers evaluated the data of over 200 partygoers who, with peak blood alcohol values of up to 2.5 grams per kilogram, had imbibed quite a few drinks. The ECG devices monitored their cardiac rhythms for a total of 48 hours, with the researchers distinguishing between the baseline (hour 0), the drinking period (hours 1-5), the recovery period (hours 6-19), and two control periods corresponding to 24 hours after the drinking and recovery periods, respectively. Acute alcohol intake was monitored by BAC measurements during the drinking period. ECGs were analysed for heart rate, heart rate variability, atrial fibrillation, and other types of cardiac arrhythmia. Despite the festive mood of the study participants, the quality of the ECGs was almost universally high throughout.

“Clinically relevant arrhythmias were detected in over five percent of otherwise healthy participants,” explains Moritz Sinner, “and primarily in the recovery phase.” Alcohol intake during the drinking period led to an increasingly rapid pulse of over 100 beats per minute. Alcohol, it would seem, can profoundly affect the autonomous regulatory processes of the heart. “Our study furnishes, from a cardiological perspective, another negative effect of acute excessive alcohol consumption on health,” stresses Brunner. Meanwhile, the long-term harmful effects of alcohol-related cardiac arrhythmias on cardiac health remains a subject for further research.

Source: Ludwig-Maximilians-Universität München

Categories : Cardiovascular DiseaseTags :

At-home Nasal Spray for Episodes of Arrhythmia

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A clinical trial led by Weill Cornell Medicine investigators showed that a nasal spray that patients administer at home, without a physician, successfully and safely treated recurrent episodes of a condition that causes arrythmia. The study, published in the Journal of the American College of Cardiology, provides real-world evidence that a wide range of patients can safely and effectively use the experimental drug etripamil to treat recurrent paroxysmal supraventricular tachycardia (PSVT) episodes at home. For many, this could spare the need for repeated hospital trips for more invasive treatments.

The study is the latest in a series of studies by lead author Dr James Ip, professor of clinical medicine at Weill Cornell Medicine and a cardiologist at New York-Presbyterian/Weill Cornell Medical Center, and colleagues to demonstrate the potential of nasal spray calcium-channel blocker etripamil as an at-home treatment for PSVT.

Patients with PSVT experience sudden and recurrent rapid heart rhythms triggered by abnormal electrical activity in the upper chambers of the heart.

Though the episodes are not commonly life-threatening, they can be frightening and cause shortness of breath, chest pain, dizziness or fainting and lead to frequent emergency department visits. Treatment for PSVT often requires hospitalisation to receive intravenous medication. Some patients undergo cardiac ablation.

Dr Ip and colleagues previously showed that almost two-thirds of patients with PSVT who took one or more doses of the calcium channel blocker etripamil without a physician present experienced symptom relief on average in 17 minutes.

The latest study builds on those findings, showing that etripamil is safe and effective under more real-world circumstances in a larger patient population, and could be safely used to treat multiple episodes of PSVT.

The new study enrolled 1116 patients at 148 sites in the United States, Canada and South America. It did not require a pretest dose supervised by a physician as the previous studies did. It also included patients with a history of atrial fibrillation or atrial flutter, who were excluded from the previous studies. Patients monitored their heart for one hour with a home electrocardiogram monitor after self-administering the first dose, took an additional dose if necessary, and were allowed to self-treat up to four PSVT episodes with etripamil. Two-thirds of the patients experienced relief within an hour, and the average time needed for symptom relief was 17 minutes. Mild, temporary nasal symptoms such as runny nose, nasal congestion or discomfort, and bloody nose were common after the first use of etripamil but became less common with subsequent use.

Source: Weill Cornell Medicine

Categories : Cardiovascular Disease Diet and NutritionTags :

Five Years of High-dose Vitamin D Reduced Atrial Fibrillation Risk

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Taking higher-than-recommended doses of vitamin D for five years reduced the risk of atrial fibrillation in older adults, according to a randomised controlled study conducted in Finland and published in the American Heart Journal.

Atrial fibrillation is the most common arrhythmia, the risk of which increases with age, and which is associated with an increased risk of stroke, heart failure and mortality. Vitamin D has been shown to have an effect, for example, on the atrial structure and the electrical function of the heart, suggesting that vitamin D might prevent atrial fibrillation.

Conducted at the University of Eastern Finland in 2012–2018, the main objective of the Finnish Vitamin D Trial (FIND) was to explore the associations of vitamin D supplementation with the incidence of cardiovascular diseases and cancers. The five-year study involved 2 495 participants, men aged 60 and older, and women aged 65 and older, who were randomised into three groups: one placebo group and two vitamin D3 supplementation groups, with one of the groups taking a supplement of 40µg (1600 IU) per day, and the other a supplement of 80µg (3200 IU) per day. All participants were also allowed to take their personal vitamin D supplement, up to 20µg (800 IU) per day, which at the beginning of the study was the recommended dose for this age group. Participants had no diagnoses of cardiovascular disease or cancer at baseline, and they completed comprehensive health-related questionnaires, both at the beginning. Data on the occurrence of diseases and deaths were also obtained from Finnish nationwide health registers. Approximately 20% of participants were randomly selected for more detailed examinations and blood samples.

During the five-year study, 190 participants were diagnosed with atrial fibrillation: 76 in the placebo group, 59 in the 40µg group, and 55 in the 80 micrograms group. The risk of atrial fibrillation was 27% lower in the 40µg group, and 32% lower in the 80 micrograms group, when compared to the placebo group. In the sub-cohort selected for more detailed examinations, the mean baseline serum calcidiol concentration, which is a marker of the body’s vitamin D concentration, was relatively high, 75nmol/l. After one year, the mean calcidiol concentration was 100nmol/L in the 40µg group, and 120nmol/l in the 80µg group. No significant change in the calcidiol concentration was observed in the placebo group.

Only two randomised trials tried to test whether vitamin D supplementation reduces AF risk in healthy adults, and they did not observe an effect when using doses of 10µg (400 IU) or 50µg (2000 IU) per day. Further confirmation of the present results from the FIND study is therefore needed before doses of vitamin D that significantly exceed current recommendations can be recommended for preventing atrial fibrillation. The FIND study has previously published findings showing no association with the incidence of other cardiovascular events or cancers.

Source: University of Eastern Finland

Categories : Cardiovascular DiseaseTags :

Repurposed Cancer Drug Might Treat Cardiac Arrhythmias

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Ruxolitinib, a drug that is already approved by the U.S. Food and Drug Administration (FDA) for treating certain cancers and skin conditions, is effective at inhibiting CaMKII, a protein kinase linked to cardiac arrhythmias.

In a new study published in Science Translational Medicine, researchers invented a new reporting technique to monitor activity of CaMKII while screening the effects of nearly 5000 FDA-approved drugs on human cells that expressed the enzyme. The screen identified five previously unknown CaMKII inhibitors; ruxolitinib, which is used to treat cancers of the blood and bone marrow, along with skin conditions like atopic dermatitis and vitiligo, was the most effective.

CaMKII, or Calcium and calmodulin-dependent protein kinase II, is critical to cardiomyocytes, the muscle cells of the heart, where it maintains the balance of calcium. Activation of CaMKII helps facilitate rapid changes in heart activity, such as initiating a fight-or-flight response in the body. Overactivation can lead to impaired heart function and cell death, which can in turn lead to poor heart health outcomes like arrhythmia.

CaMKII is perhaps best known, however, for its role in the brain, where it is believed to play key roles in learning and memory. This has slowed the development of CaMKII inhibitors to treat arrythmia, for fear they could impact cognitive function.

“Finding an FDA approved drug means that millions of people have been taking CaMKII inhibitors, and in the case of ruxolitinib, there are no reported major problems with the brain,” said Mark Anderson, MD, PhD, a senior author of the paper. “That should give pharma and biotech companies confidence that they could carry out development of a CaMKII inhibitor program, because the biggest obstacle seems to be surmountable.”

The research began in Anderson’s lab at Johns Hopkins University Oscar Reyes Gaido, the study’s first author and an MD-PhD student in the lab, developed a new tool to measure activity of CaMKII in living cells. He started with a protein called green fluorescent protein (GFP), originally derived from jellyfish, that emits green light. He then engineered the GFP tag to detect CaMKII activation, making a new reporter called CaMKAR (CaMKII Activity Reporter). When this reporter was inserted into human heart cells, it helpfully glowed bright green whenever CaMKII became active, allowing researchers to monitor enzyme activity.

“This biosensor will be very useful for studying how CaMKII activity changes in both healthy and pathological contexts. Existing methods can measure CaMKII activity, but they lack the versatility and resolution to track in real time and with high sensitivity,” Reyes Gaido said. “This has been a real obstacle for studying enzyme biology in general, so this gives the field an important new tool.”

Using this tool, the researchers conducted a drug repurposing screen to test the effects of 4,475 approved compounds on cultured human cardiomyocytes. This identified five previously unknown CaMKII inhibitors: ruxolitinib, baricitinib, silmitasertib, crenolanib, and abemaciclib. Of the five, ruxolitinib was the most effective at inhibiting CaMKII activity in cell and mouse models of CaMKII-driven arrhythmias. A 10-minute application of the drug was enough to prevent catecholaminergic polymorphic ventricular tachycardia (CPVT), a congenital source of pediatric cardiac arrest, and rescue atrial fibrillation, the most common clinical arrhythmia. Crucially, the mice treated with ruxolitinib did not show any adverse cognitive effects when they were tested with memory and learning tasks.

Anderson said that new drugs based on ruxolitinib could be used in several ways to treat heart conditions. One would be what he called the “pill in a pocket” scenario. In the early stages of atrial fibrillation, people could take the medication occasionally as symptoms arise. Patients with CPVT are often resistant to standard treatments, and a ruxolitinib-based treatment could provide another option. Finally, there is evidence that inhibiting CaMKII during a heart attack can prevent heart muscle from dying, so emergency responders could potentially administer such a drug as part of standard practice.

“There’s been a long search for fundamental pathways that could be targets for therapeutics in arrhythmias,” Anderson said. “This could be a finding that will translate relatively rapidly into people now since it’s already been proven to be safe in humans.”

Source: University of Chicago

Categories : Cardiovascular DiseaseTags :

e-Cigarette Chemicals can Cause Heart Arrhythmias

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Researchers have found that exposure to e-cigarette aerosols can cause heart arrhythmias in animal models – both in the form of premature and skipped heart beats. The study findings, published in Nature Communications, suggest that exposure to certain chemicals in e-cigarette liquids (e-liquids) promote arrhythmias and cardiac electrical dysfunction.

“Our findings demonstrate that short-term exposure to e-cigarettes can destabilise heart rhythm through specific chemicals within e-liquids,” said Alex Carll, assistant professor in the UofL Department of Physiology who led the study. “These findings suggest that e-cigarette use involving certain flavors or solvent vehicles may disrupt the heart’s electrical conduction and provoke arrhythmias. These effects could increase the risk for atrial or ventricular fibrillation and sudden cardiac arrest.”

The researchers tested the cardiac impacts of inhaled e-cigarette aerosols solely from the main two ingredients in e-liquids (nicotine-free propylene glycol and vegetable glycerin) or from flavoured retail e-liquids containing nicotine. They found that for all e-cigarette aerosols, the animals’ heart rate slowed during puff exposures and sped up afterwards as heart rate variability declined, indicating fight-or-flight stress responses. In addition, e-cigarette puffs from a menthol-flavoured e-liquid or from propylene glycol alone caused ventricular arrhythmias and other conduction irregularities in the heart.

This work adds to a growing body of research on the potential toxicity and health impacts of e-cigarettes reported by the American Heart Association Tobacco Regulation and Addiction Center, for which UofL serves as the flagship institute.

“The findings of this study are important because they provide fresh evidence that the use of e-cigarettes could interfere with normal heart rhythms – something we did not know before,” said collaborating researcher Professor Aruni Bhatnagar. “This is highly concerning given the rapid growth of e-cigarette use, particularly among young people.”

As e-cigarette use has grown nationwide, the potential advantages and harms of vaping have been debated. Since vaping does not involve combustion, it exposes users and bystanders to little if any carbon monoxide, tar or cancer-causing nitrosamines compared with conventional cigarettes. However, e-cigarettes can deliver aldehydes, particles and nicotine at levels comparable to combustible cigarettes. Vaping might help smokers quit combustible cigarettes, but the appeal and addictiveness of e-cigarettes may encourage youth to vape amidst unknown long-term risks or take up smoking. More than 25% of high schoolers and 10% of middle schoolers in the U.S. reported using e-cigarettes before the pandemic.

“Our team’s findings that specific ingredients in e-cigarette liquids promote arrhythmias indicates there is an urgent need for more research into the cardiac effects of these components in both animals and humans,” A.Prof Carll said.

Source: University of Louisville

Categories : Cardiovascular Disease COVIDTags :

Possible Cause of COVID Arrhythmias Discovered

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Anatomical model of a human heart
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The SARS-CoV-2 virus can infect cardiac pacemaker cells, causing the cells to undergo self-destruct by ferroptosis according to a preclinical study reported in Circulation Research. This may explain the heart arrhythmias that are commonly observed in COVID patients.

In the study, the researchers used an animal model as well as human stem cell-derived pacemaker cells to show that SARS-CoV-2 can readily infect pacemaker cells and trigger a process called ferroptosis, where cells self-destruct, releasing damaging reactive oxygen molecules.

“This is a surprising and apparently unique vulnerability of these cells — we looked at a variety of other human cell types that can be infected by SARS-CoV-2, including even heart muscle cells, but found signs of ferroptosis only in the pacemaker cells,” said study co-senior author Professor Shuibing Chen.

Arrhythmias, including tachycardia and bradycardia, has been observed in some COVID patients, and multiple studies link these arrhythmias to worse COVID outcomes. But how the coronavirus caused these remained unclear.

In the new study, the researchers examined golden hamsters (one of the only lab animals that reliably develops COVID-like signs from SARS-CoV-2 infection) and found evidence that following nasal exposure, the virus can infect the sinoatrial node, which is the natural cardiac pacemaker.

The researchers then induced human embryonic stem cells to mature into cells closely resembling sinoatrial node cells. They showed that these induced human pacemaker cells can be infected by SARS-CoV-2 as they express ACE2 receptors. Large increases in inflammatory immune gene activity were also seen in the infected cells.

The team’s most surprising finding, however, was that the pacemaker cells, in response to the stress of infection, showed clear signs of a cellular self-destruct process called ferroptosis, which involves accumulation of iron and the runaway production of reactive oxygen molecules. The scientists were able to reverse these signs in the cells using compounds that are known to bind iron and inhibit ferroptosis.

“This finding suggests that some of the cardiac arrhythmias detected in COVID patients could be caused by ferroptosis damage to the sinoatrial node,” said co-senior author Dr Robert Schwartz

While COVID patients could in principle be treated with ferroptosis inhibitors specifically to protect sinoatrial node cells, antiviral drugs that block the effects of SARS-CoV-2 infection in all cell types would be preferable, the researchers said.

The researchers plan to continue to use their cell and animal models to investigate sinoatrial node damage in COVID and other settings.

“There are other human sinoatrial arrhythmia syndromes we could model with our platform,” said co-senior author Dr. Todd Evans. “And, although physicians currently can use an artificial electronic pacemaker to replace the function of a damaged sinoatrial node, there’s the potential here to use sinoatrial cells such as we’ve developed as an alternative, cell-based pacemaker therapy.”

Source: Weill Cornell Medicine

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Radiation Therapy Can Reprogram Faulty Heart Cells

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Photo from Olivier Collett on Unsplash
Photo from Olivier Collett on Unsplash

New research published in Nature Communications suggests that radiation therapy can reprogram heart muscle cells to what appears to be a younger state, fixing electrical problems that cause life-threatening arrhythmia without the need for an invasive catheter ablation procedure.

In catheter ablation, a catheter is threaded into the heart, and the tissue that triggers ventricular tachycardia is burned, creating scars that block the errant signals. The new study, however, shows that noninvasive radiation therapy can reprogram the heart muscle cells to a younger and perhaps healthier state, fixing the electrical fault in the cells themselves without needing scar tissue to block the overactive circuits. Previous research showed that radiation therapy typically reserved for cancer treatment could be directed at the heart to treat ventricular tachycardia.

Radiation therapy could in theory reproduce the scar tissue of catheter ablation, in a quicker and totally noninvasive procedure, making the treatment available to more severely ill patients. The doctors found that, surprisingly, patients experienced large improvements in their arrhythmias just days to weeks after radiation therapy, much quicker than the months it can take scar tissue to form after radiation therapy, suggesting that a single radiation dose diminishes the arrhythmia without forming scar tissue. Analysis showed the radiation treatment was at least as effective as catheter ablation for certain patients with ventricular tachycardia, albeit for different, unknown reasons.

“Traditionally, catheter ablation creates scar tissue to block the electrical circuits that are causing ventricular tachycardia,” said senior author and cardiologist Stacey L. Rentschler, MD, PhD, an associate professor of medicine, of developmental biology and of biomedical engineering. “To help us understand whether the same thing was happening with radiation therapy, some of the first patients to have this new treatment gave us permission to study their heart tissue – following heart transplantation or if they had passed away for another reason, for example. We saw that scar tissue alone could not explain the remarkable clinical effects, suggesting that radiation improves the arrhythmia in some other way, so we delved into the details of that.”

Radiation treatment triggered heart muscle cells to begin expressing different genes, the researchers found. Increased activity was seen in a signaling pathway called Notch, which is known for its vital role in early development, including in forming the heart’s electrical conduction system.

A single dose of radiation temporarily activates Notch signalling – normally dormant in adult cells – and leading to a long-term increase in sodium ion channels in the heart muscle, a key physiologic change that can reduce arrhythmias.

“Arrhythmias are associated with slow electrical conduction speeds,” Rentschler said. “Radiation therapy seems to kick up the speed faster by activating early developmental pathways that revert the heart tissue back into a healthier state.”

The researchers studied these effects in mice and in donated human hearts. In human samples, the researchers found that these changes in heart muscle cells were only present in areas of the heart that received the targeted radiation dose.

“Radiation does cause a type of injury, but it’s different from catheter ablation,” said co-author and radiation oncologist Julie K. Schwarz, MD, PhD, a professor of radiation oncology and director of the Cancer Biology Division in the Department of Radiation Oncology. “As part of the body’s response to that injury, cells in the injured portion of the heart appear to turn on some of these early developmental programs to repair themselves. It’s important to understand how this works because, with that knowledge, we can improve the way we’re treating these patients and then apply it to other diseases.”

The researchers also found that the beneficial effects of radiation continued for at least two years in surviving patients. And importantly, they were able to demonstrate in mice that a lower dose of the radiation produced the same effect. A lower radiation dose could reduce long-term side effects and allow such treatment in other types of heart arrhythmias. And while Notch was a big player in these effects, Prof Schwarz said it’s not the only pathway involved. The researchers are continuing to investigate how radiation triggers heart cells to revert to a healthier state.

Source: Washington University School of Medicine

Categories : Cardiovascular DiseaseTags :

Study Links Poor Sleep to Arrhythmias

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A large observational study linked poor sleep to arrhythmias, although genetic risk factors for rhythm problems appeared to lessen the association.

The results, published in the American College of Cardiology, show that best self-reported sleeps (getting 7-8 hours etc) had a 29% lower risk of developing atrial fibrillation or flutter and a 35% lower risk of bradyarrhythmia compared with those with the worst sleep patterns (eg, being a night owl, sleeping too little, snoring, and having insomnia or daytime drowsiness).

The ventricular arrhythmia risk fell away after demographic, lifestyle, and genetic risk factors were accounted for.

Together with previous research linking a healthy sleep pattern to reduced cardiovascular disease and heart failure risks, the findings, according to the researchers, “emphasise the importance of improving the overall sleep behaviours in the prevention of cardiovascular disease at an early stage among the high-risk populations”.

Being reversible, the findings support the idea of better sleep for arrhythmia prevention.

“However, rest assured, we must not yet lose sleep over their findings,” cautioned Alan Kadish, MD, and Jason Jacobson, MD, in an accompanying editorial. They drew attention to a number of limitations, making the findings more theoretical than currently practicable.

Despite the study’s more sophisticated approach, “a major limitation is that arrhythmia diagnoses were obtained from diagnostic codes,” they noted. Furthermore, arrhythmias are subject to significant variability.
Arrhythmia prevention doesn’t mean cardiovascular disease prevention, they added. “[N]ot all arrhythmias have the same significance, and many are the consequence (not cause) of cardiovascular disease,” they wrote. “Alternatively, sleep disorders and arrhythmias may both simply be indicators of declining health overall and not causally linked.”

The researchers proposed potential mechanisms of action including disrupted autonomic nervous balance of sympathetic nervous and vagal outflows and metabolic changes.

The editorialists pointed out the interesting finding that genetic predisposition to atrial fibrillation significantly modified the associations. Good self-reported sleep and low genetic risk together presented a 46% lower risk of atrial fibrillation than a poor sleep pattern plus high genetic risk.

Progressively poorer sleep health scores were associated with higher incidences of atrial fibrillation and bradyarrhythmias.

Sleeping 7 to 8 hours per day, infrequent or no insomnia, and no frequent daytime sleepiness were each linked to lower arrhythmia risk.

Source: MedPage Today