Almost a quarter (22 per cent) of 36 cardiac arrest survivors had genetic mutations that explained why their seemingly healthy heart had malfunctioned, a new study by researchers at the University of Sydney’s Centenary Institute and Royal Prince Alfred Hospital found.
Finding the cause meant survivors and family members with the same inherited mutations could be treated to prevent future potentially fatal episodes, lead author cardiologist Dr Julia Isbister said.
For the majority of these patients (88 per cent) the mutations were in genes linked to cardiomyopathy, despite their heart looking physically normal on the usual tests.
Had these survivors never been genetically tested they would not have known why they had suffered a near-fatal arrest or that their families were also at risk, senior author, and director of RPA’s Genetic Heart Disease Clinic Professor Chris Semsarian said.
“These are young people – some in their teens and 20s – who on a particular day had a cardiac arrest and for so long we didn’t know what the reason was,” he said.
“You can do every test under the sun and you don’t find anything wrong with their heart. It looks normal, but it carries genetic mistakes.”
Without genetic testing, any medical team may come to the conclusion a cardiac arrest was likely to be a freak event, requiring no ongoing treatment, leaving patients vulnerable to a possibly fatal second attack.
The genetic testing was detecting “concealed cardiomyopathies”, and could be used as an early-warning system that the heart’s electrical system was short-circuiting.
The study authors suspect patients such as James Medway will develop outward signs of cardiomyopathy years later, such as an enlarged or thickening of the heart.
“This is precision medicine in action – using genetics to pinpoint the precise cause of the disease, screen their families and find targeted treatments that may be as simple as lifestyle changes or medication or it may be an implanted defibrillator, but it’s all geared towards preventing sudden death in the future,” Dr Semsarian said.
Mr Medway was in peak physical condition – “fantastically fit”, the Olympic rowing hopeful says – as he trained at the Australian Institute of Sport’s training centre in northern Italy in 2019.
Then he blacked out.
When he was roused from an induced coma two days later, his teammates had to fill him in.
The 27-year-old had finished his warm-down after intense training. Just as he unstrapped his feet from a rowing machine he collapsed, hitting his head on the ergometer.
“It was such a pivotal, live-or-die moment,” Mr Medway said.
The rower knew he was lucky. Had he been training on the lake, had one of his teammates – a doctor – not immediately suspected his heart and not his head injury was the critical concern, and the medical team not been nearby with a defibrillator, he could have died.
But after exhaustive testing, his heart looked normal for an elite athlete – slightly on the larger side, and healthy. Within a week, he was fitted with an implantable cardioverter-defibrillator and less than two months later he was back training.
“There was a chance this was just a freak accident and I definitely still had the dream of getting to the Olympics and winning a medal,” he said.
But Professor Semsarian, one of Mr Medway’s doctors, knew there was a small chance the episode had a genetic cause. Testing confirmed it.
Mr Medway had arrhythmogenic cardiomyopathy linked to a genetic mutation, which is estimated to affect one in 5000 people, most of whom never have a cardiac episode.
But elite-level sport was out of the question.
“It was a lot to take in,” Mr Medway said. “I prided myself on being a really fit and healthy person, and the fact that I never got sick or injured. Now something I excelled at was no longer good for me.
Sudden cardiac arrest in Australia
Roughly 33,000 Australians have a sudden cardiac arrest every year; 9 per cent survive. The vast majority of cases are people over 35 with coronary heart disease and well-established risk factors like smoking and high blood pressure.
Younger patients with these unexplained cardiomyopathies are uncommon, and most can avoid having one of these near-death experiences. But for those who do, the ramifications can be tragic.
“Looking back, it would be very easy to slip into the mentality where everything I was working towards has been taken away … but I’m so lucky to have had that experience,” said Mr Medway, who has launched into a career he loves as an investment banking analyst.
The scientists have so far genetically tested 11 first-degree relatives of survivors. Five had the same inherited genetic mutations and six were given the relieving news that they did not, the International Journal of Cardiology reported.
Dr Isbister said genetic testing could provide the answers when all other causes have been excluded, but guidelines – written about a decade ago – don’t support this approach.
“What we have seen here is that there is perhaps more utility for patients with no clinically identified causes to have genetic testing now that our knowledge of cardiac arrest and genetics has advanced and we can cast a wide [genetic testing] net to get answers for patients,” she said.
The authors suggested all sudden cardiac arrest survivors under the age of 50 could have an assessment to determine whether genetic testing was warranted.
Professor Jason Kovacic, executive director of the Victor Chang Cardiac Research Institute, said the research showed the benefits of comprehensive genetic testing.
“It does indicate that we can potentially save lives here,” he said.
But the single-centre study of 36 patients was not likely to be enough to alter diagnostic practice, he said.
“It’s a challenge to recruit thousands of patients because – while always a tragedy – this is relatively uncommon in our community,” Professor Kovacic said.
“Whether this will tip the scale to make [cardiology] committees change their guidelines is yet to be determined.”
In one Indian study, PPI was used in 66.6% of the patients. Such rampant use of PPI costs almost 10% to 20% of total expenditure on medicines spent by patients. Many physicians were found to be ignorant of the adverse effects of PPI associated with inappropriate prescribing of the agents. (1,2,3).
PPIs ( including Pantoprazole, Omeprazole, Rabeprazole, Lansoprazole etc) can be safely used daily for 14 days with no more than 3 such treatment courses in a year. However, the concern is that they are used/prescribed frequently ignoring the detrimental effects of chronic use of these medications. The administration of short-term PPI is usually well tolerated. Prolonged use of PPIs has, however, been noted to raise the risk of infection, osteoporosis, and other severe adverse reactions such as hypomagnesemia, fractures etc.
Magnesium deficiency US FDA issued a warning in 2011 regarding the risk of hypomagnesia after chronic use of PPI. Low amounts of magnesium can lead to muscle stiffness, spasm, arrhythmias, and seizures. Hypomagnesemia treatment includes supplements with magnesium. However, in people who keep going to use PPIs, this does not necessarily resolve hypomagnesemia. As per the FDA, Hypomagnesemia occurrence is possibly minimal for a course of PPI for 2 weeks up to 3 times a year. Nevertheless, PPIs that are administered at a higher dosage for 6 months, can result in magnesium deficiencies.
Physicians and clinicians should recommend assessment of serum magnesium especially in patients likely to be on these medicines for extended periods of time, and other patients taking PPIs with medicines like digoxin, diuretics, or medicines that could induce hypomagnesemia. This is particularly necessary for people receiving digoxin since low magnesium will enhance the risk of severe adverse events such as arrhythmia. (4)
Risk of Bone fractures A retrospective observational analysis published in Nature found that patients with type 2 diabetes on chronic PPI use, irrespective of dosage, demonstrated a 40 percent higher risk of hip fracture relative to non-users with type 2 diabetes. (5) Vitamin B12 deficiency In a major case-control analysis reported in JAMA, vitamin B12 deficit was more observed in people who received PPI for more than 2 years, and the amounts of over 1.5 pills a day were directly correlated with the disorder.
Vitamin B12 deficiency if not treated can lead to dementia, neurocognitive damage, anemia, and many other health issues. For distal -ileum absorption, gastric acid is required to release vitamin B12 from dietary proteins. Nevertheless, in individuals consuming PPIs, vitamin B12 concentrations are not regularly monitored. (6)
Resistant Diarrhea PPIs may be linked to an increased risk of Clostridium difficile infection, which has high morbidity and mortality. Diagnosis of Clostridium difficile should be suspected in patients on PPI presenting with non-resolving diarrhea and abdominal discomfort. FDA advised discontinuing PPI in such patients. The vegetative form of Clostridium difficile generally survives in an alkaline environment after PPI use. Moreover, altered gut microbial habitat makes the patients susceptible to develop such infections. (7)
Diabetes Recently published study in Gut, active PPI users have a 24% greater chance of developing diabetes compared to non-users, as well as the risk of developing diabetes rose with the length of PPI use. Thus, when recommending PPIs, particularly for long-term usage, precaution is advised. (8)
Renal dysfunction Patients consuming PPI are more likely to develop AKI and CKD than nonusers. Studies have corroborated the findings in people taking PPIs twice per day as opposed to once a day dose. (9) Short term use of PPI may be beneficial for the patients when clinically indicated. However, its chronic use is certainly associated with its harmful effects. With the backdrop of all these existent studies of PPI (and more undergoing studies) highlighting its adverse effects, it is the need of the hour to modify our practice of prescribing PPI which has become one of the most commonly bought over the counter drugs. At the same time, it has become imperative to impart adequate patient education regarding the possible adverse effects associated with PPI. A well-informed clinician can only change the patient’s practice of routinely taking PPI as over-the-counter drug.
The study, performed in sophisticated experimental mouse models, shows that the cardioprotective effect of metoprolol during a heart attack is not shared by other beta-blockers commonly administered by intravenous injection, such as atenolol and propranolol. The study has been published in the European Heart Journal. Metoprolol is a member of the beta-blocker class of drugs that has been in use for more than 40 years.It is comparatively a cost effective drug.
The study [1] was led by Dr Borja Ibáñez, head of Clinical Research at the CNIC, a cardiologist at Fundación Jiménez Díaz University Hospital, and a CIBERCV group leader. The research “demonstrates that metoprolol has unique cardioprotective properties and heralds a paradigm change in cardiology and the treatment of acute myocardial infarction,” said Dr Ibañez. In 2013, the METOCARD-CNIC clinical trial, led and coordinated by the CNIC, showed that administration of metoprolol very early during an infarction limits damage to the heart and reduces long term consequences.
Four years later, in 2017, the same research team showed how and why this cheap and simple therapeutic strategy is so efficient. In a study published in Nature Communications, the researchers showed that the cardioprotective potential of metoprolol lies in its ability to block the action neutrophils–inflammatory cells activated during infection to eliminate pathogens–preventing them from entering the infarcted heart tissue.
Now, in 2020, the team has shown that metoprolol’s cardioprotective properties are not shared by other beta-blockers and are thus not a class effect. “The study presents important results that update and refine cardiovascular pharmacotherapy and underline how important it is not to assume that drugs in the same class will have identical activities and clinical indications,” said pharmacist Agustín Clemente, a doctoral candidate at the CNIC and first author on the article. Acute myocardial infarction is one of the main manifestations of cardiovascular disease and is the leading cause of death in the world. In Spain, more than 70 000 people have a heart attack every year. Current treatment guidelines recommend early administration of beta-blockers to patients with symptoms of an infarction but do not distinguish between the different drugs in this class. This is why the new results are so clinically significant. Neutrophils, as well as protecting against infection, can become hyperactivated in other situations, such as during a myocardial infarction, when they can cause significant additional injury to the heart. Metoprolol is able to limit this hyperactivation, thereby preventing inflammatory damage associated with infarction.
The study also assessed the effects of different beta-blockers in other models of inflammatory disease, like lung damage and peritonitis. In all models examined, metoprolol was the only beta-blocker able to limit the organ damage inflicted by hyperactivated neutrophils. These findings could have an impact on the treatment of diseases in which injury is linked to neutrophil hyperactivation, including sepsis and possibly even COVID-19. Building on the knowledge generated about metoprolol’s cardioprotective effect, the research team used 3D intravital microscopy to investigate the effect of the drug on neutrophils. “This advanced imaging technology allowed us to study changes in cell movement and shape induced by metoprolol and to exclude a direct effect on these cells of other intravenous beta-blockers like atenolol or propranolol,” explained Agustín Clemente. Working with the CNIC Bioinformatics Unit, the research team conducted computational studies to assess the impact of different beta-blockers on type 1 beta adrenergic receptors, the molecular target of these drugs.
“Unexpectedly, we found that despite their related chemical structures each drug interacts with beta-1 adrenergic receptors in a different way. This translates into a distinct structural change in the receptor for each drug, which in the case of metoprolol induces a specific molecular cascade and a concrete and unique cellular effect,” commented co-principal investigator Dr Eduardo Oliver, a CNIC and CIBERCV pharmacologist and beneficiary of the Comunidad de Madrid talent program. “Unlike other beta-blockers, metoprolol triggers a change in the intracellular structure of the beta-1 adrenergic receptor, opening it up so that it can interact with other nearby proteins that mediate the unique effect of metoprolol on neutrophil activity,” added Dr Oliver. Until now, beta-blockers were thought to act exclusively by impeding interaction between epinephrine and beta-1 adrenergic receptors.
But the new results demonstrate that the binding of metoprolol not only blocks the action of epinephrine, but also activates other intracellular pathways, a phenomenon called biased agonism. The authors conclude that metoprolol should be the beta-blocker of choice in clinical practice. “If these results are confirmed in future clinical studies, this would herald a change in the clinical guidelines for this devastating disease, placing metoproplol, and not other beta-blockers, as the drug of choice for patients suffering a heart attack,” said Dr Ibañez. The low cost of metoprolol, at less than 2 euros for an acute dose, brings additional value to this discovery.
The fear of catching COVID-19 is making people doubly cautious about their health and safeguard it by all means. While some have been relying on traditional home remedies like kadha and other detox drinks to stay healthy, many have also taken to self-medication- from Vitamin C, Vitamin D, to multivitamins, there has been an exponential rise in people stocking up on ‘immunity-boosting’ medicines.
COVID-19 infection, the fear of hospitalization, the need for isolation and the stigma has pushed the panic button for a lot many. For many, social media has also turned into an online pharmacy and a way for people to “borrow” medical prescriptions and depend on advice from internet pals to self-treat their problems. In order to ‘boost and protect’ health, people have started taking supplements, herbs and easily available OTC medications, such as aspirin, antihistamine and paracetamol tablets by themselves. The problem of self-medication has been reported so widely, it has actually led people to avoid testing altogether, exposing others to the risk too.
Medications work on a case-to-case basis, especially for a disease as critical as COVID-19. A medicine which may prove useful for one, may not be suitable for another. Self-medication may also, at times, bring on additional health problems. Any medicine or remedy which does not have a doctor’s backing is potentially harmful, especially for those living with a co-morbidity. Medicines only work the best when they are used in a certain followed dose, advised by a medical practitioner. If not, it can wreck the body’s immune system and leave bad repercussions. The same goes for your helpful cup of kadha. Just because it has immunity-boosting or symptom-relieving benefits, doesn’t mean it’s all for the best. Overconsumption, or having more than required can pose problems for your body. For example, a man in America sadly passed away after having too much of mulethi (liquorice). An Indian doctor’s tweet about a healthy patient shedding ‘buckets of blood’ after a home remedy thinning his blood supply also went viral recently. Drinking too much kadha can also ‘warm’ your body and result in blisters, ulcers and burn your tongue since most of the ingredients used in traditional concoctions are hot in nature. In some cases, it could also result in stomach disorders, which could pose additional problems.
As for immunity boosters and vitamins, there are simple checks that can tell you their efficacy. Vitamins and minerals are most helpful when absorbed properly, had at the right time of the day. For example, Vitamin C pills available in the market are mostly sold in ascorbic acid form, which is not as effective as the ascorbate form. Excess consumption of another booster, zinc tablets could also induce lethargy. The same risks exist for Vitamin D and other trace minerals. Moreover, excessive consumption of superfoods like haldi or ashwagandha (which is being sold in the form of pills) won’t help much.
While it’s absolutely vital to keep your immunity up in the times of the pandemic, simply relying on pills and medicines to “prevent” or cure the infection isn’t a good solution. Prevention, and cutting down on your risk of exposure, along with proper disinfection habits are really the best way to fight and negate the risks of COVID-19.
As for our immunity, our bodies really are the best judge to tell us what we need to do. Proper sleep, a good nutrient-rich diet and exercise are three of the best natural infection fighters and work better than any supplement. Hence, listen to your body before overdosing on medicines and supplements. If you think you might be deficient in any of the vitamins, worried about your diet or have pre-existing medical conditions, a consultation with a medical expert would do you a lot of good. Always follow your doctor’s advice before googling your medical conditions on the internet.
A study by University College London (UCL) of 590 people who lost their sense of smell or taste earlier in the year found 80% had coronavirus antibodies. Of those people with antibodies, 40% had no other symptoms. The research only looked at people with mild symptoms, however.
Evidence that loss of smell and taste could be signs of coronavirus began to emerge from about April, and they were added to the official list of symptoms in mid-May. Current guidance states anyone who experiences a loss of, or change to their sense of smell or taste should self-isolate and apply for a test. But lead author of the UCL study, Prof Rachel Batterham, says cough and fever are still seen by many as the main symptoms to look out for. She recruited people between 23 April and 14 May by sending out texts via four GP surgeries in London, enrolling those who reported losing their smell or taste in the previous four weeks. All of these participants were tested for antibodies, and four out of five were positive, suggesting a previous Covid-19 infection.
The study was constrained by the fact that all its participants had mild symptoms, including or limited to a loss of smell or taste, so they may not be representative of all Covid patients. But its findings emphasise the importance of people looking out for any change to their sense of smell or taste, and self-isolating if they realise they can’t smell “everyday” items like perfume, bleach, toothpaste, or coffee, Prof Batterham said. While not all coronavirus patients will necessarily lose their sense of smell, if you do lose your sense of smell it is highly likely to be coronavirus, this research seems to suggest. The thing to look out for is a loss of smell without having a blocked or runny nose, Prof Batterham explained. This is distinct from the experience of having a cold where smell and taste might be altered because a person’s airways are blocked. King’s College London researchers, who run the Covid Symptom Study app, previously estimated 60% of people with coronavirus lost their sense of smell or taste.
Although this is considered a milder symptom and unlikely to land someone in hospital, Prof Batterham points out the potential dangers of losing your sense of smell including not being able to detect smoke, leaking gas or food that has gone off. If suffered longer term, it can also have a significant impact on people’s quality of life. Thousands of people online have reported worrying experiences including causing fires and not being able to smell the smoke. Some have noticed constantly smelling a rancid “garbage” odour or experiencing a metallic taste, while others have found themselves unable to taste food for months after being clear of the virus. The group of people who only lose their smell without experiencing any other symptoms may also pose the “greatest risk” to others since they may feel generally well and carry on going about their daily lives, Prof Batterham pointed out. Although the two often go together, loss of or change to smell was more common than loss of taste among people who have recovered from coronavirus, she said. Her research took place at a time when loss of smell and taste were not recognised symptoms of the virus.