Latest news with #dilated cardiomyopathy
Medscape
5 days ago
- Health
- Medscape
Testing for LMNA Mutations Called ‘Woefully Underutilized'
People with mutated copies of the LMNA gene are at high risk for cardiac laminopathies, including atrioventricular block and atrial or ventricular arrhythmias (VAs) leading to dilated cardiomyopathy. These autosomal dominant mutations have a high penetrance, meaning that a high percentage of persons with a pathogenic or likely pathogenic variant will develop health problems related to the gene. For those with cardiac manifestations, about 90% of carriers of LMNA mutations older than 30 years have a high risk for sudden death from arrhythmia — even patients with minimal left ventricular dilation and mild systolic impairment — well before the onset of heart failure. A long-term follow-up study from 122 consecutive carriers of LMNA mutations with cardiac conditions showed that most had experienced arrhythmia, heart block, embolic events, or heart failure within 7 years of diagnosis. Could some outcomes, such as sudden cardiac death, be averted with a more precise view of LMNA mutations? New research published in JAMA Cardiology shows pinpointing the type and location of the LMNA mutation may guide clinicians toward earlier treatment approaches to improve prognosis for these high-risk patients. These interventions might include earlier placement of implantable cardioverter-defibrillator (ICD) devices and family testing to detect the mutation before the onset of symptoms. 'Genetic testing for dilated cardiomyopathy is woefully underutilized,' said the paper's senior author, Neal Lakdawala, MD, an associate professor of medicine at Harvard Medical School and a cardiologist in the Heart and Vascular Center at Brigham and Women's Hospital, in Boston. In fact, claims data showed that fewer than 2% of patients with dilated cardiomyopathy undergo genetic testing. 'Prior research has established the prognostic power of a genetic diagnosis,' Lakdawala told Medscape Medical News . 'We took it one step further within a specific genetic etiology, to show that the type of gene variant and the location of a gene variant also matter.' The retrospective cohort study examined international registry data from 718 patients (mean age, 41.3 ± 14.3 years) with pathogenic or likely pathogenic variants of LMNA . The participants in the study had no prior history of malignant VA. The primary outcome was time to malignant VA, defined as sudden cardiac death, placement of an ICD, or other manifestations of hemodynamically unstable VA. The secondary outcome, advanced heart failure, was defined as nonsudden cardiac death, implantation of a left ventricular assist device, or heart transplant. Reflecting the high risk associated with LMNA mutations, Lakdawala said, nearly one third of the study participants experienced sudden cardiac death, hemodynamically unstable VA, or an ICD procedure during the 4.2-year follow-up period. In addition, 15% developed advanced heart failure, defined as the implantation of a left ventricular assist device, heart transplant, or nonsudden cardiac death. These outcomes occurred despite many patients having a baseline left ventricular ejection fraction (EF) in the normal range (mean EF was 56%, well above guideline-recommended thresholds of 35%-45% for ICD placement, the researchers reported). Looking deeper into the genes, Lakdawala and his colleagues found participants who had truncating LMNA variants — an abbreviated version of the protein — had worse arrhythmic outcomes, regardless of the position of this genetic mutation on the DNA sequence. On the other hand, those who exhibited missense variants of the LMNA gene — an altered amino acid on the DNA sequence — had a lower risk for harmful arrhythmias and better overall outcomes. Taken together, the location and nature of the gene variants could lead to specific predictions of cardiac risk, according to the researchers. A man with an EF of 50% and a truncating LMNA gene variant, for example, would have a 12% risk for VA within 5 years, but a 7.2% risk if a missense variant were present. For a woman with EF 50%, this risk would be 7.5% for a truncating variant vs 4.5% for a missense variant, if no other risk factors were present. Why Genetic Testing Is Key In an editorial accompanying the journal article, Sharlene M. Day, MD, a cardiomyopathy specialist and presidential professor at the Perelman School of Medicine at the University of Pennsylvania, in Philadelphia, wrote 'the data from this study can also inform risk stratification even in healthy populations with incidental or secondary findings.' Integrating genetic findings into cardiomyopathy management should be 'a priority for all practicing cardiologists,' she wrote. 'The knowledge gap appears to be narrowing with respect to the importance of genetic testing in patients with cardiomyopathies,' Day told Medscape Medical News . 'But there's still opportunity to improve recommendations and referrals by cardiologists for genetic counseling and testing.' Testing typically consists of a broad panel identifying multiple gene variants, including LMNA , she said. If a gene variant is found in an individual patient, cascade testing of family members for that variant is often recommended. 'The current research study nicely highlights the impact of identifying not only the specific gene involved but the type of variation within that gene in terms of risk stratifying patients for adverse outcomes,' she said. Impact on Future Cardiology Guidelines Future clinical practice guidelines should emphasize the value of a genetic diagnosis for risk stratification in patients with dilated cardiomyopathy, especially for predicting sudden death and heart failure, Lakdawala said. The most recent guidelines on heart failure from the American College of Cardiology and the American Heart Association list a class 2A recommendation for placement of an ICD in patients with high-risk genes for dilated cardiomyopathy and an EF of 45% or lower, adding that primary preventive ICD may be considered for those with higher EF. The 2023 European Cardiomyopathy Guideline recommends placement of ICDs in patients with LMNA variants and an EF above 35% (class 2A if risk factors are present and class 2B if no risk factors are present). 'For updated guidelines, I think the most immediate impact would be to refine the LMNA risk score for ventricular arrhythmias to include the type and location of the LMNA variant,' Day told Medscape Medical News . 'Genetic testing has clinical ramifications that will help cardiologists take better care of their patients,' Lakdawala added. 'The take-home message is that they should order these tests!' Lakdawala reported receiving personal fees from Alexion, Bayer, Bristol Myers Squibb, Cytokinetics, Lexeo Therapeutics, Nuevocor, Pfizer, and Tenaya Therapeutics and grants from Bristol Myers Squibb and Pfizer. Day reported serving as chair of the steering committee for Lexicon Pharmaceuticals, on the data monitoring committee for Cytokinetics, and receiving grants from Bristol Myers Squibb.
BBC News
10-07-2025
- Health
- BBC News
'Both my daughters needed new hearts from organ donors'
A mum from Surrey who was not on the organ donor register until her two young daughters needed heart transplants has said she realised "how important it is" after her children spent time on the waiting to new figures by NHS Blood and Transplant, 8,096 patients were on the transplant waiting list as of 31 March - the highest number on record. This record number includes 95 people in Surrey and does not include the 3,883 patients suspended due to being unfit for transplant or temporarily Perry, from Leatherhead, said she owed both her daughters' lives to organ donors and called for more people to be on the register. Her daughters Lucie and Isobel, now 16 and 10 respectively, have each had a heart transplant after being diagnosed with dilated cardiomyopathy, a condition where the left ventricle becomes enlarged and Perry told Radio Surrey that Lucie was diagnosed "out of the blue" at the age of two, before Isobel was confirmed to have the same condition during a check up seven years Lucie's diagnosis, she said: "I went from being with the GP in the morning to that in the evening... it's a lot to get your head around."Going through the process again with Isobel was "horrific", Mrs Perry got a new heart within eight days of being listed, while Isobel - who had complications prior to joining the list - waited just 10 days. Mrs Perry said the disease meant both children had enlarged hearts."It meant that there was more space for a larger heart... so they could have an older child's heart," she in hospital with Isobel, she said the stark reality became apparent."There were four children waiting for hearts, and two of them didn't make it," she that she wasn't previously on the donor register, Mrs Perry said that these experiences shifted her perspective."I believe you can't be willing to take something without being willing to give back," she said. "My daughters would have both died if they hadn't got that heart... we got very lucky, twice." Opt-in system Dave Webb from Walton-on-Thames now lives a full life, but it was an entirely different story just six years ago as the 52-year-old awaited a new Webb was born with hypertrophic cardiomyopathy, a condition in which muscle tissues of the heart become thickened without an obvious cause."In my adult years - in my 20s onwards - I begun to realise that I did have some symptoms and I couldn't function as well as, say, other people," he told BBC Radio 52-year-old's deteriorating condition meant that he reached a crossroad by his mid-40s."If I didn't receive a transplant, I wouldn't last for many more years," he Webb was "very, very fortunate" to only be on the waiting list for four weeks, and after receiving a new heart at the age of 46, said he felt completely getting back into sport, he spends time meeting other transplant patients and has really relished "celebrating the gift of life that we've been given".Referencing the opt-in system that has been in place since 2020, Mr Webb says the most important thing is that people "make their wishes known" to family."They hold the ultimate key, because when something does happen, they have to be referenced and they have to agree," he added.
