Latest news with #heartfailure
The Sun
10 hours ago
- Health
- The Sun
The cheap 90p supplement that could slash risk of deadly heart failure by ‘reversing' damage from silent killer
A CHEAP supplement could help prevent deadly heart failure by 'reversing' damage caused by silent killer diabetes. People with type 2 diabetes who took the widely available pill daily on top of their standard treatment were able to reverse early signs of diabetes-related heart failure in a matter of months, a new study showed. 1 The number Brits with diabetes has reached an all-time high - it's estimated that 5.8 million people have the condition, 90 per cent of whom have type 2 diabetes. This number is predicted to continue surging. Type 2 diabetes patients are up to five times more likely to develop heart failure than the rest of the population, according to the British Heart Foundation (BHF). Once someone with diabetes is diagnosed with heart failure, they are three times more likely to die over the next five years. But a study conducted by the University of Leeds found that diabetics who took mitoquinone - sold as a health supplement for about 90p per tablet - had healthier hearts after four months compared to those not given the supplement. Lead author Dr Henry Procter, a clinical research fellow at the University of Leeds, said: 'These encouraging results are a sign that mitoquinone could keep hearts healthier for longer in people with diabetes. "If the study had continued for longer, it is likely we would have started to see differences in more serious indicators of heart health between the group with mitoquinone and the group without.' Diabetes causes problems with how the body - including the heart - processes and uses energy, which can cause stress and damage to the cells of the heart muscle. Over time, it can lead to the heart stiffening and being unable to pump blood well, eventually to the point of heart failure. Mitoquinone is an artificial antioxidant that is thought to guard cells against this metabolic stress and damage. It's sold online as a supplement for about £50 for a jar of 60 pills, which works out at about 86p per tablet. However, these are at doses far lower than those used in the study. The research, whose results were presented at the British Cardiovascular Society conference in Manchester, involved 70 patients with type 2 diabetes who didn't have heart failure. Half were given 40mg of mitoquinone per day on top of their regular diabetes treatment, while the other half received their usual medication. Both groups had their heart health assessed at the start of the study and again four months later. After four months of mitoquinone, diabetic patients' hearts were able to process and use energy 15 per cent more efficiently. Their heart muscles were also able to relax more quickly, which showed that early indicators of stress and stiffness in their hearts had been reversed, according to researchers. Patients experienced no side effects from taking the supplement. What is heart failure and tips to prevent it Heart failure is a condition where your heart can't pump blood around your body as well as it should. It doesn't mean your heart has stopped working but you may need support to help it work better. When your heart isn't pumping blood as well as it should, it means you're not getting enough oxygen. This affects how your body works, including your breathing and muscles. This causes some of the main symptoms of heart failure, like: Fainting or feeling lightheaded Feeling increasingly tired or weak at rest which gets worse with movement New persistent cough Shortness of breath when you're active or resting Swelling in your feet and ankles which can spread to your lower body You should see your GP as soon as you can if you experience any of these symptoms. To manage heart failure, here are some things you could try: Keeping active – which has been proven to boost energy and improve sleep and quality of life. Keeping to a healthy weight and diet – this will help your overall health and prevent extra strain on your heart. Limiting how much alcohol you drink (less than the recommended 14 units per week) - lowering your chance of getting abnormal heart rhythms, high blood pressure and diseases such as stroke, liver problems and some cancers. Stopping smoking and using other tobacco products - reducing your risk of developing heart and circulatory diseases. Watching the amount of fluid you have each day if advised by your medical team. Weighing yourself regularly – sudden weight gain may mean too much fluid is building up in your body and will need treated. Source: BHF Those who didn't take the daily pill didn't see the same improvements to their heart health. Experts said that while their findings are promising they now need to be backed up by larger trials. The research team is now looking into running a larger study of mitoquinone in diabetes patients, to gather more evidence that the supplement could protect their hearts and prevent heart failure over time. They hope to show that diabetes patients could one day be prescribed mitoquinone to keep their hearts healthier for longer. 'We hope that a larger study will continue to demonstrate the benefits of this antioxidant, and that one day soon diabetic patients can be prescribed it to help prevent heart failure before it ever affects their lives," Dr Procter said. Professor Bryan Willians, the BHF's chief scientific and medical officer, added: 'This study presents some intriguing initial findings. "It's still early days for this research and the results will need to be confirmed in a larger scale trial. "The study neatly demonstrates why it is so important to continue to support research and look for solutions in a wide variety of places, so that we can continue to offer hope to people living with, and at risk of, cardiovascular disease.'
BBC News
15 hours ago
- General
- BBC News
'I'm terrified I'm going to drop down dead from heart failure'
A man who was only told he was suffering from heart failure seven years after tests were first carried out has said he was left "terrified" by the McKenna was living in Peterborough in 2018 when he organised an appointment at his local GP surgery for tests after experiencing chest pains, shortness of breath and swelling in his said he never heard back from the surgery but, after a move to Scarborough in 2023, he received a letter from his new GP about an annual check-up "due to his heart failure".Mr McKenna, now 58, said it was a "shock" to discover his condition by letter - and especially so long after the original tests. "Out of the blue, my partner said 'you've got a letter from the doctor'," he said."I was at work and told her to to open it - she said I'd got heart failure, which was a shock to find out that way."He added: "If I'm supposed to have an annual check, where have the other six been?"Mr McKenna became worried about the diagnosis after seeing a BBC report documenting the rise in poor heart health. According to the British Heart Foundation (BHF), there has been a 23% increase in the number of people aged between 20-64 dying of heart and circulatory diseases in Yorkshire since 2019."I've never smoked, I've had maybe five to ten units of alcohol since Christmas, which is well below the national standard," Mr McKenna said."I think over the age of 30 or 35 there should be annual [heart] screening." 'I've been forgotten' The patient has since had six blood tests, two ECGs and a chest X-ray but felt no further along in understanding his diagnosis. "On my records, apparently I was meant to have been put on blood thinners and beta blockers but I've had no medication," he said. The former security worker continued: "Through Covid I worked for the heart and lung hospital in Cambridge - I know how hard the NHS work, but it seems to be that I've been forgotten."I'm terrified I'm going to drop down dead."His former surgery did not respond to a request for comment by the Health, which runs his current GP practice, said: "We note that the patient has stated that they were not made aware of a diagnosis by their previous GP practice a number of years ago. "This patient joined our SSP practice in 2024 and since that time we have acted in accordance with the NICE guidelines to ensure he has received appropriate care in relation to any conditions that he may have." Listen to highlights from North Yorkshire on BBC Sounds, catch up with the latest episode of Look North.
Daily Mail
a day ago
- Health
- Daily Mail
Major study finds 90p supplement could slash risk of sudden heart death: 'Reverses' signs of deadly disease
A cheap supplement could help prevent potentially deadly heart failure among patients with type 2 diabetes, research suggests. More than 5million people in the UK are thought to suffer from type 2 diabetes, which is often referred to as a 'silent killer', with rates having soared in recent years. But now scientists have found patients taking a substance called mitoquinone—sold as a health supplement for about 90p per tablet—had healthier hearts than those in a control group. Scientists behind the study said the results could save lives given how patients with type 2 diabetes have five times the risk of suffering heart failure compared to someone without the condition. In the trial, patients on mitoquinone even had signs that the damage their hearts had suffered from diabetes had been 'reversed'. However, experts have said while their findings are promising they now need to be backed up by larger trials. Mitoquinone is an artificial antioxidant—a substance that helps protect cells—which is a modified version of an antioxidant naturally found in the body called CoQ10. Dr Henry Procter, an expert in heart health at University of Leeds and lead author of the four month study, said the results were 'encouraging'. 'If the study had continued for longer, it is likely we would have started to see differences in more serious indicators of heart health between the group with mitoquinone and the group without,' he said. 'We hope that a larger study will continue to demonstrate the benefits of this antioxidant, and that one day soon diabetic patients can be prescribed it to help prevent heart failure before it ever affects their lives.' In the trial, the results of which were presented at the British Cardiovascular Society conference in Manchester, involved 70 patients with type 2 diabetes without heart failure. Half were given 40mg of mitoquinone per day in addition to their regular diabetes treatment, while the other half just received their usual medication. Both groups had their heart health assessed at the start of the study and again four months later. At the end of the trial the group on mitoquinone were found to have hearts that performed 15 per cent more efficiently than at the start of the study. The mitoquinone group were also found to have improvements in exercise tests, with their hearts also able to relax more quickly after exertion. Researchers said these were signs that the stress and stiffness the organ suffers from diabetes had been reversed. Diabetes damages the heart by interfering with how the organ processes and uses energy. Over time this interference causes stress and harms the cells of the heart muscle, leading to it becoming stiff and having to work harder to pump blood around the body, increasing the risk of heart failure. Mitoquinone is thought to help protect the cells from this damage. The substance is sold online as a health supplement for about £50 for a jar of 60 pills, which works out at about 86p per tablet. However, these are at doses far lower than those used in the study. Critically, no adverse side effects were reported in the group taking mitoquinone. The scientists are now hoping to run another similar trial with a larger group of patients to add more weight to their findings. If the results are supported by future studies the experts hope diabetes patients could one day be prescribed mitoquinone to help protect their hearts for longer. Heart failure is an incurable condition where the organ can't pump blood around the body as well as it should. The condition tends to get worse over time and is often eventually fatal. Once a diabetes patient is diagnosed with heart failure it triples their risk of dying within the next five years. Reacting to the study, Professor Bryan Willians, chief scientific and medical officer at the charity the British Heart Foundation, said it was a promising start. 'It's still early days for this research and the results will need to be confirmed in a larger scale trial,' he said. 'The study neatly demonstrates why it is so important to continue to support research and look for solutions in a wide variety of places, so that we can continue to offer hope to people living with, and at risk of, cardiovascular disease.' Almost 6million Britons have diabetes, of which 90 per cent is type 2, but charities estimate 1.2million are living with the disease undiagnosed. While nationally, an estimated 8 per cent of the population of England has the disease, this rises to over one in 10 people in some parts of the country. Type 2 diabetes occurs when the body doesn't make enough insulin or the insulin it makes doesn't work properly. Insulin is a hormone critical to controlling blood sugar levels. Having high blood sugar levels over time can cause heart attacks and strokes, as well as problems with the eyes, kidneys and feet. Sufferers may need to overhaul their diet, take daily medication and have regular check-ups. Symptoms of the condition, which is diagnosed with a blood test, include excessive thirst, tiredness and needing to urinate more often. But many people have no signs.
The Independent
3 days ago
- General
- The Independent
Coroner has ‘no doubt' diagnosis could have prevented death of baby boy
A coroner has said there were 'missed opportunities' from 'many' medical visits which could have saved the life of a one-year-old boy. Archie Squire died from heart failure in the early hours of November 23 2023, after successive cardiac arrests, days after his first birthday. He was suffering from a rare heart defect in which the heart's lower half is reversed, which was never diagnosed despite at least 16 visits to medical staff in his 368 days of life. On Friday, the inquest at Kent and Medway Coroner's Court in Maidstone, heard that if Archie had been diagnosed earlier he would 'almost certainly not have died at the time he did'. Area coroner Sarah Clarke said: 'I have no doubt earlier recognition and diagnosis of a very rare heart condition would have made a difference to the outcome for Archie. 'There are many points in the chronology where there were missed opportunities to do something differently to make the diagnosis of Archie's condition more likely.' Archie's parents made repeated visits to Queen Elizabeth the Queen Mother (QEQM) Hospital in Margate, Kent, and to St James' Surgery in Dover, with concerns about Archie's breathing and constipation which did not lead to long-term diagnoses. The coroner continued: 'He died as a direct result of heart failure with an underlying congenitally corrected transposition of the great arteries – a rare condition that could have been diagnosed by an echocardiogram. 'Despite many presentations to medical personnel in the weeks and months leading up to his death, an echocardiogram was not undertaken.' His mother, Lauren Parrish, from Dover, recalled her son being labelled a 'mystery child' because doctors were not sure what was wrong with him. 'It felt like every time we sought medical help for his breathing he was diagnosed with some form of chest infection,' Ms Parrish said in a statement read by the coroner. Ms Clarke added that if a diagnosis had been found for Archie 'he would almost certainly not have died at the time that he did'. A report by paediatric cardiac surgeon Professor David Anderson noted an 'unacceptable' delay in Archie receiving an echocardiogram after being referred to QEQM by a GP on October 6. He wrote: 'If his diagnosis had been correctly made, he almost certainly would not have died when he did.' It added that 'the delay in obtaining an echo was unacceptable'. Last week, Ravindra Kumar, a paediatric registrar at QEQM responsible for Archie on the night he died, cried in court describing how his work has changed since Archie's death. Asked what he would do differently, Dr Kumar said: 'I regret talking about Archie's condition in front of the family to others, to my colleagues, I learned a big lesson to be more compassionate.' Medical records and Dr Kumar's witness statement suggest he did not see Archie between 9.30pm and 1am on the night he died, the inquest heard. Archie's godmother Nikki Escudier read a pen portrait of Archie to the court. She said: 'Archie Squire was a shining light. A little boy whose laughter, love and joy touched everyone lucky enough to know him. 'Born on November 20 2022, Archie brought happiness into the world from the very beginning. 'In just 368 precious days, he filled every moment with warmth, laughter and the kind of love that stays with you forever. 'His smile lit up the room and his presence left a lasting mark on every heart he touched.' The coroner commended Archie's family on their support for each other throughout the process, and has asked the East Kent Hospitals Trust to provide further evidence of their updated action plans and procedures since Archie's death. At the conclusion of the inquest, Tracey Fletcher, chief executive of East Kent Hospitals, said: 'We offer our sincere condolences to Archie's family. We can only imagine the pain they have endured and we are truly sorry that we did not identify Archie's condition earlier. 'After meeting with Archie's family, we have made important changes to our service. These include one standard process for triage and booking of child referrals, and prioritising the assessment of children referred to us. We will examine further learnings identified through the inquest process. 'Staff across the trust now receive specialised training to improve how clinical concerns, diagnoses and plans are discussed with families in our care. The training for our children's health team specifically draws on lessons learned from Archie's death.'
Medscape
4 days ago
- Health
- Medscape
May 30 2025 This Week in Cardiology
Please note that the text below is not a full transcript and has not been copyedited. For more insight and commentary on these stories, subscribe to the This Week in Cardiology podcast , download the Medscape app or subscribe on Apple Podcasts, Spotify, or your preferred podcast provider. This podcast is intended for healthcare professionals only. In This Week's Podcast For the week ending May 30, 2025, John Mandrola, MD, comments on the following topics: listener feedback, CRT vs CSP, important clues on the ECG, beta-blocker interruption after myocardial infarction, novel approaches to LDL-C lowering, and ICD decisions in cardiac sarcoidosis. Dr Steve Dickson, a heart failure cardiologist from Kansas City, writes via email to push back on my skepticism about rapid initiation of guideline-directed medical therapy (GDMT) in heart failure (HF). Dr Dickson says I am right about the STRONG-HF trial, which used cardiologists for the majority of follow-up visits. And while cardiologist-led care may currently be the case in many clinics across the country, he writes, times are changing. Hospitalists, primary care practitioners (PCPs), and advanced practice practitioners are becoming more comfortable with these life-saving medication classes. The future of heart failure care isn't just the burden of cardiologists, but internal medicine where there are more reinforcements. Dr Dickson says that in his clinic they run a '4 Weeks 4 Meds' program for patients with heart failure with reduced ejection fraction (HFrEF), mainly through nurse practitioners that he guides and manages. He says it's 'quite aggressive but I can assure you my CEO loves seeing his readmissions drop.' My comment to this is that I fully support programs like '4 weeks 4 meds' programs. It's a great idea, but of course, it takes administrative support, incentives. And, I would add that this is a great use of advanced practice clinicians. I say congratulations and I hope more programs like this become a reality. Clearly, HF care would improve if it did. The obvious advantage of such a program is not only getting more patients on max GDMT but also avoiding harm from overzealous GDMT titration. Cardiac Resynchronization Therapy vs Conduction System Pacing – CONSYST-CRT As many of you know, because I have said it so many times, the most exciting thing in EP right now is not ablation but pacing, specifically, conduction system pacing (CSP). I saw a Tweet this week, saying that ablation has become more anatomic and rote, and pacing is becoming more physiologic. It used to be the opposite. In an ablation, we would map and study electrophysiology, and in pacing we would simply flop a catheter in the right ventricle (RV) and we would just screw it in wherever it fell into the RV. Now in ablation we put in a pulsed field ablation (PFA) catheter and boom. E-grams are gone. PFA ablation is ruining EP. Now, during a pacemaker we meticulously record and pace in areas of the conduction system. 6+ years ago, we were doing it with the His bundle, and now it's the left bundle. To do CSP is to bathe yourself in beautiful physiology. But beautiful images of CSP on an ECG are not evidence. What we need is evidence that it is superior to biventricular (BiV) pacing for the treatment of patients with heart failure and left bundle branch block (LBBB). The thing is, in BiV pacing, we have strong evidence, from multiple trials, that biV pacing reduces hard outcomes, like mortality, compared to standard RV implantable cardioverter defibrillators (ICDs) or medical therapy. We think, emphasis on think, that because CSP narrows the QRS, and some smaller studies have shown improved hemodynamics with CSP, it is similar to, or superior to, BiV pacing. We need trials. Well, I am a local principal investigator here at my hospital for the US government-funded Left vs Left trial, which will have death and hospitalization for heart failure (HHF) as a primary endpoint. Planned enrollment is 2100 patients and follow-up is for 5 years. That's a long time to wait. This month, JACC EP has published another attempt to compare CSP to BiV pacing in CRT-eligible patients. Spanish investigators have now published the CONSYST-CRT trial. This was a randomized controlled trial (RCT) of just 134 patients of CSP vs BiV pacing. The design was non-inferiority of CSP. The primary endpoint was a composite of many things: death, transplant, HHF, or a left ventricular ejection fraction (LVEF) improvement of less than 5% at only 12 months. I hope you are seeing the problems: I will go over the issues in the comments. First finding: 18 of 67 patients crossed over from CSP to BiV pacing. Second finding: 23.9% in the CSP group had a primary outcome event vs 29.8% of the BiV pacing. The absolute risk difference was –5.9%. The confidence interval went from –21.2%, which is far better with CSP, to 9.2% worse for CSP. The accepted non-inferiority margin was 10% worse, and so 9% is less than 10% and this allowed a claim of non-inferiority with a P value of .02. Secondary endpoints also favored CSP. QRS narrowing was better in the CSP arm. Echo response was better, as was a NYHA functional class improvement. The combined endpoint of death, transplant, and HHF also showed non-inferiority, though I could not find confidence intervals on the difference. The authors concluded: CSP was non-inferior to biV pacing in achieving clinical and echocardiographic response, suggesting that CSP could be an alternative to biV pacing. I laud trials and clinicians who attempt them. CSP vs biV pacing is an important question. But if you are going to experiment on people, you need to have a chance of telling a difference. There is no way this trial had a chance with only 134 patients—1 in three who crossed over—to detect signal from noise. There were 16 vs 20 primary outcome events, respectively. There were 1 vs 3 deaths, 0 vs 1 transplant, and 8 vs 10 HHF. The most common outcome was failing to improve an ejection fraction (EF), which is far from a hard clinical outcome. That is a tiny number of events. Not only was the composite endpoint problematic, but follow-up for a year is totally inadequate. Left vs Left is asking the same question and enrolling 2000 patients — almost 20 times more patients. It would have been fine to compare hemodynamics, but we have oodles of these studies showing similar effects on EF with CSP. I mean no malice to the Spanish team, and to be sure, I was part of the His-SYNC trial, another woefully underpowered trial, but this type of effort tells us little to nothing about the long-term effects of the two strategies. Underpowered trials, I think, should be avoided. Since the beauty of the ECG is what got me interested in cardiology, I am always on the lookout for studies on the ECG. A UCSF group reports a research letter in Circulation EP on the association between a fragmented QRS and myocardial fibrosis burden and autopsy-defined arrhythmic causes among presumed sudden cardiac death (SCD). QRS complexes should be sharp and narrow. There should be no notches or fragments. This is a report from the ongoing project called the POST SCD or 'Postmortem Systematic Investigation of Sudden Cardiac Death' study. The idea is to use autopsy and clinical data to adjudicate arrhythmic (potentially treatable with an ICD) vs nonarrhythmic death (overdose, pulmonary embolism, stroke, etc). So far, the team has had 943 presumed SCD, of which 402 had ECGs before death. And 98 (or about 1 in 4) of these had histogical data. Fragmented QRS was defined as greater than 1 notch for QRS <120 milliseconds (ms) and >2 notches if the QRS ≥120 ms and fragmented QRS's had to be in 2 leads. The findings of this research letter were: Presumed SCD with a fractionated QRS on more than 1 lead were more likely to have arrhythmic causes compared with presumed SCDs without fractionated QRS 76% versus 55%; odds ratio, 2.6 [95% CI, 1.11–6.5]; P = .036, No other ECG marker was associated with higher odds of arrhythmic death. Coronary artery disease (CAD) was the most common cause of fractionated QRS. Presumed SCDs with fractionated QRS in greater than 1 lead had higher mean total and replacement fibrosis as well as more interstitial fibrosis burden than presumed SCDs without fractionated QRS ( P < .05 for all). I cover this imperfect study because the value of the ECG is under-recognized. I say imperfect because only half the presumed SCD had ECGs before death; and only a fraction of these had histological samples. What's more, the difference in associations were statistically significant but the positive and negative predictive value of fractionated QRS is surely low. But I want to consider this a public service announcement to my colleagues in cardiology. When you are sorting out whether a patient (say with syncope or near syncope) has a worrisome structural heart condition, study the QRS. When someone is telling me the story of syncope, my first question after the story is what does the QRS look like? Fragmented QRS is an electrical manifestation of disordered ventricular conduction, which is often due to scar, and disordered conduction, aka, anisotropy, sets the stage for reentry. Recall one of the fundamentals of cardiology: reentry requires three things: two pathways, delayed conduction, and unidirectional block. Scar sets the stage because there all three possible. In the same way that atrial structural disease increases the odds that a PAC fibrillates the atria, ventricular structural disease makes it more likely that a PVC fibrillates the ventricle. No, I am not saying that every notched fragmented QRS is malignant, but it's a clue, it's one piece of data. Don't overreact, but don't ignore the QRS. EHJ has a substudy from the French ABYSS trial of beta-blocker (BB) interruption vs continuation after myocardial infarction (MI). The substudy purported to show 'spikes' in HR and blood pressure (BP) after BB discontinuation. And this explains why the ABYSS study failed to show that stopping beta-blocker therapy could be safely done in stable post-MI patients. None of this is correct. None. And I want to correct the record about ABYSS, again. In my mind, ABYSS is entirely consistent with the REDUCE-AMI trial of not using BB in the post-MI patient. REDUCE-AMI found that not giving long-term BB resulted in similar major adverse cardiovascular events (MACE) outcomes compared with standard BB in post-MI patients with a normal EF. The main ABYSS trial, published in NEJM in August 2024, compared interruption of BB or continuation of BB in patients who had a previous MI and EF > 40% and MI at least 6 months before randomization. The median time from MI to randomization was just about 3 years. ABYSS enrolled about 3700 patients. It had a non-inferiority (NI) design with a 4-point composite endpoint of MI, stroke, death, or hospitalization for cardiac reason. The NI margin was a difference of 3% points for the upper bound of the 95% CI. The results were that interruption was not only not non-inferior to continuation but actually inferior to continuation. The numbers: 23.8% primary outcome events in the interruption group vs 21.1% primary outcome events in the continuation group Absolute risk increase of 2.8% with 95% CI that went from 0.1 to 5.5. Since 5.5% was greater than the NI margin of 3%, NI was not met. And when you looked at the CI, the entire 95% CI was above 0 for the interruption group so it was actually inferior. But, But. The entire composite was driven by hospitalization for cardiac reasons — 349 vs 307. There were no differences in death, no difference in MI, and no difference in stroke. The major MACE outcomes were nearly identical. The only reason ABYSS found to be against interruption was a surrogate outcome requiring adjudication of hospitalization. The less biased outcomes of death, stroke, and MI were identical. Now to the EHJ substudy, which looked at changes in BP and HR from baseline to post-randomization in the two groups. They also assessed the changes in HR and BP impact on the primary endpoint for the prespecified subgroups of patients with or without history of hypertension. With little to no surprise the BB interruption group sustained an increase in heart rate (about 10 bpm) and systolic blood pressure (SBP) (3.7 mmHg). These deltas remained stable after discontinuation over months. With regard to the hypertension (HTN) and no-HTN groups which were almost 50-50 split, there were largely similar effects. That was an increase in heart rate and SBP. Also not surprising was that the primary outcome occurred more often in patients with HTN than those without HTN, showing that HTN patients are higher risk. I am not sure we needed that analysis because HTN is a known risk factor. The observed harm (higher rate of the primary outcome) was numerically higher in the HTN group; the difference was not statistically significant. In other words, there was no evidence of a heterogenous treatment effect for HTN or no HTN. But remember, 'harm' as described by the primary outcome in ABYSS is flawed because it was driven only CV hospitalizations. In Table 2, the authors show the results of the components of the primary outcome in the BB interruption and continuation arm based on the subgroup of HTN — and in MI, stroke, and death, the P values for interactions were close to 1, as in absolutely no difference. The authors concluded: Interruption of beta-blocker treatment after an uncomplicated MI led to a sustained increase in BP and HR, with potentially deleterious effects on outcomes, especially in patients with history of hypertension. My friends, the ABYSS trial was a perfectly nice trial. It addressed an important question. The problem was the choice of endpoint. When you look at MI, stroke, and death, BB interruption was totally fine. This substudy showing why ABYSS found harm is flawed because the main trial chose a flawed endpoint. Further, finding that HR and BP go up slightly when a BB is stopped is like finding out you get wet when walking in the rain. BB reduce HR and BP. When you stop them, HR and BP go up a bit. Since the main trial found no increase in MACE, we can say that that small rise in HR and BP don't have deleterious effects. The most we can take from this study is that there does not seem to be a heterogenous treatment effect for the presence of HTN. I think we can stop BB in patients with a history of MI if they have normal EF and no other reason to take BB. The one caveat to my argument that death, MI, and stroke were not different was that it was a little underpowered. For the composite of death, MI, and stroke, the hazard ratio was 0.96 in the interruption vs continuation arm, but the confidence interval went from 0.74 to 1.24. So, interruption could be 26% better or 24% worse than continuation. And perhaps that is why the authors decided to add CV hospitalizations. Yet when you combine the data from REDUCE-AMI and recent observational data from Denmark, the ABYSS finding of no increase in MACE after BB interruption supports the idea that interruption of BB after MI is reasonable and safe. And, of course, less medicine is better. Is Lifelong LDL-C Lowering Within Reach? The heart-1 Gene-Editing Trial Heart-1 Gene Therapy Trial Pauses Enrollment JACC has published a phase 2 dose-ranging study with another oral PCSK9 inhibitor, called AZD0780. In other words, it doesn't have a name yet. The drug has a novel mechanism, which I won't delve into at this point, but it did achieve a dose-dependent drop in LDL cholesterol (LDL-C). The max dose of 30 mg achieved a 50% placebo-adjusted reduction of LDL-C and all patients were on statins but had LDL-C > 70 mg/dL. No adverse effects were noted but the study was quite short at only 12 weeks. The accompanying editorial was quite good. I learned a lot from it. First, there are multiple oral PCSK9 inhibitors in development. I think this is a good thing because pills are better than shots. I say that because shots increase the work of being a patient. There is just more inertia and insurance restrictions and effort required to take a shot, however infrequently. The editorialists also discussed the pricing dilemma and the role of pharmacy benefit managers (PBM) whose rebate-based pricing models often dictate drug availability. To be honest, I don't quite understand PBMs well enough to explain them, but I can say that I don't get the feeling they contribute much to the health of US citizens. There is also a potential — and I emphasize the potential part — for permanent inhibition of the PCSK9 complex via CRISPR/Cas9-mediated gene editing. Dr Sekar Kathiresan's company Verve Therapeutics is working on that, and it has progressed to early-stage human trials. The one-and-done approach to LDL-C management is obviously a high reward, high risk strategy and there will need to be rigorous safety data before this could become a reality. Two safety issues have arisen: one a patient developed very high hepatic enzymes, and in another trial, two patients had serious cardiac events — not felt to be due to the intervention. So we shall see. There would have to be a heck of lot more data on safety before I signed up to permanently change my genes — especially when you can accomplish the same thing with a tiny daily pill. I know that I sound old saying this, but if you stop and think, it's quite shocking that such an approach could be close to becoming a possibility. Editing genes so as to reduce LDL-C, for life. Wow. One of the toughest calls in EP is deciding on ICD treatment of patients with suspected cardiac sarcoid. It's hard for many reasons, not least because the diagnosis of cardiac sarcoid, and its risk stratification is difficult. European Heart Journal has published a nice study from a Dutch center and two American centers. They had about 1500 patients with biopsy proven sarcoid, mostly non-cardiac who had not had ventricular tachycardia (VT) and therefore were being considered only for a primary prevention ICD. They then compared outcomes based on multiple ways to risk stratify. I, for instance, did not know that there were multiple professional societal recommendations for an ICD. There is the 2014 Heart Rhythm Society (HRS) statement, the 2017 AHA/ACC guideline and the 2022 European Society of Cardiology (ESC) guideline. And they're all a little different. The purpose of this study is that Dutch and American authors propose is that cardiovascular magnetic resonance imaging (CMR) phenotyping is better. CMR phenotyping sounded tricky but it they made it seem easy. You are either CMR high or low risk. It's based on EF and 'pathology frequent LGE'. There were four CMR phenotypes: (1) no late gadolinium enhancement (LGE) and normal LVEF, (2) no LGE and abnormal LVEF, (3) pathology-frequent LGE, and (4) pathology-rare LGE. Pathology-frequent LGE included at least one of four features: sub-epicardial, multifocal, septal, and right ventricular free wall involvement. They then dichotomized CMR phenotypes into high-risk (pathology-frequent LGE) and low-risk (no LGE and normal LVEF, no LGE and abnormal LVEF, or pathology-rare LGE) phenotypes. The next step was to follow the 1500 or so patients over 5-10 years for VT events. Of note, most were young, average age 54 years. Let me stop there and say when you have a 50-something year old with heart block, before putting in a pacemaker, stop and think about sarcoid. Do a CMR first. The first finding was that when an ICD was indicated based on either the society or CMR phenotype the likelihood of a ventricular arrhythmia (VA) event at 10 years was high. Ranging from 20% to 35% for the high risk CMR group. When an ICD was not indicated by either the society recommendations or CMR phenotype, the rates of VA were low, but ranged from 5% in the HRS statement to 2.6% for CMR low risk. They key findings were seen in Figure 3: the CMR dichotomized method had the best are under the curve (AUC). At 5 years, it was 0.86 for VT events. That's pretty darn good, and statistically better than each of the professional society criteria for ICD. The problem of course is that the ICD need is imperfect. A subgroup of the 1500, about 8% or 119 patients received a loop recorder. About a third had high risk CMR and two thirds had CMR low risk. 4 of 38 patients (or 4% per year) had VT in the CMR high risk 1 of 81 patients in the CMR low-risk had a VA for a 0.4% per year risk. This illustrates the problem of prediction: most high-risk patients do not have a VT event and not every low-risk patient remains free of VT. As it is ischemic and non-ischemic HF patients. I do like the CMR approach, though. And this study is quite nice, as there were more than 1000 patients, all with biopsy-proven sarcoid, good follow-up, and centrally adjudicated blinded CMR. There were — as always — limitations. ICD therapy as a VT event is not always a surrogate for SCD. Just because a person has VT therapy (shock or anti-tachycardia pacing) does not mean it was aborted SCD. Second, patients without ICDs in this study may have had VT and it went undetected. To me, if we had some replication or confirmation of such a simple CMR high- or low-risk strategy, it would seem best. Realizing of course the imperfect nature of prediction of VA events. The things to keep in mind with ICD therapy is that a) it is not an insurance policy; insurance policies confer no risk to the policy holder, and ICDs surely do; b) you always want to deploy an ICD in a patient with a high-risk of the primary outcome (the VA) and a low-risk of competing risks, such as severe HF, or dementia or chronic kidney disease, or a host of disease seen in the elderly. The 54-year-old patient with heart block and LGE and reduced EF seems like an ideal patient for an ICD.
