Mimickers of chronic thromboembolic pulmonary hypertension on imaging tests: a review
VANISH2 Bolsters Data Backing VT Ablation In Ischemic Cardiomyopathy
SAN DIEGO, CA—Catheter ablation for ventricular arrhythmias is beneficial for patients with ischemic cardiomyopathy, affirms a new meta-analysis updated to include the VANISH2 trial results.
Compared with medical management, ablation was associated with lower rates of recurrent ventricular arrhythmias, implantable cardioverter-defibrillator (ICD) shocks, ventricular tachycardia (VT) storm, hospitalization, and major adverse cardiac events, Girish Nair, MBBS (University of Ottawa Heart Institute, Canada), reported here at Heart Rhythm 2025.
The addition of the positive VANISH2 trial to the evidence base "reinforces that catheter ablation is superior to medical management," Nair said. "It has refined the estimation of catheter ablation for management of ventricular arrhythmias, and due to the difficulty of replicating the trial, it probably strengthens our conviction that catheter ablation does work in this situation."
Results from VANISH2, released in November 2024, showed that first-line catheter ablation reduced a composite of death or serious arrhythmia outcomes compared with antiarrhythmic drugs in patients with ischemic cardiomyopathy, clinically significant VT, and an ICD.
Dhanunjaya Lakkireddy, MD (Kansas City Heart Rhythm Institute and Research Foundation, Overland Park, KS), abstract chair for the Heart Rhythm Society, said catheter ablation is an important strategy that should be considered to reduce the overall morbidity associated with ventricular arrhythmias.
"There is this concept that VT ablations are difficult, VT ablations are complex, and that before you consider VT ablation, somehow people have to go through a whole barrage of antiarrhythmic drugs," he told TCTMD, adding that the side effects of those medications are "grossly underappreciated in the real world."
What this new analysis suggests, Lakkireddy said, is that "early intervention could potentially change the trajectory of how these patients are going to do."
Incorporating VANISH2
Ventricular arrhythmias are associated with adverse outcomes like death and ICD shocks, which can cause posttraumatic stress disorder and even severe depression in some patients, said Nair.
For many years, the only treatment for ventricular arrhythmias was antiarrhythmic drugs, but catheter ablation has since been used to reduce overall arrhythmia burden, VT storm, ICD shocks, and adverse outcomes like heart failure, hospitalization, and death. There are, however, only a limited number of RCTs assessing the impact of VT ablation.
Nair and his colleagues added the VANISH2 results to a meta-analysis with the prior trials of VT ablation to see how they influenced the strength of the evidence. The pooled cohort included 10 trials and 1,440 patients, with 29% of them coming from VANISH2. Composite primary endpoints varied across the trials and included outcomes like all-cause or CV death, VT storm or recurrence, appropriate ICD shock, hospitalization for ventricular arrhythmia or congestive heart failure, and major treatment-related complications.
[VANISH2] has refined the estimation of catheter ablation for management of ventricular arrhythmias. Girish Nair
A meta-analysis without VANISH2 did not show a significant reduction in composite primary outcomes with VT ablation versus medical management (risk ratio [RR] 0.76; 95% CI 0.55-1.07). The addition of VANISH2, however, narrowed the confidence interval and provided a significant difference favoring ablation (RR 0.81; 95% CI 0.66-0.99).
Catheter ablation also was associated with lower risks of the following outcomes:
There was no difference between the ablation and medical management groups in mortality (RR 0.91; 95% CI 0.72-1.14). Nair noted that none of the included trials were powered to detect a difference in mortality and that these types of patients often have multiple comorbidities that result in competing death risks.
Nair acknowledged some limitations of the meta-analysis, including the relatively low numbers of trials and participants; differences in trial methodology and interventional strategies across studies; and differences in competing CV risk factors among the participants stemming from variations in inclusion/exclusion criteria and follow-up duration.
Guideline Changes Coming?
Christine Albert, MD (Cedars-Sinai Medical Center, Los Angeles, CA), study discussant and past president of the Heart Rhythm Society, noted that there are already indications for VT ablation in practice guidelines, pointing to a class I recommendation for catheter ablation in patients with an ICD and sustained VT despite treatment with amiodarone in the 2022 European Society of Cardiology guideline on ventricular arrhythmias and sudden cardiac death.
VANISH2 adds to the literature by providing data on ablation as a first-line approach over antiarrhythmic drug therapy, Albert said.
Early intervention could potentially change the trajectory of how these patients are going to do. Dhanunjaya Lakkireddy
But Albert also highlighted several limitations of the current meta-analysis related to the differences among the trials in patient mix, ablation protocols, control treatments, and composite outcomes. When heterogeneous studies are pooled, "sometimes it doesn't work very well," she said. "Combining studies with different populations, interventions, and outcomes really can sometimes even obscure real treatment effects or can lead to misleading results."
The findings appear to show a benefit of ablation, Albert indicated. "But basically, VANISH2 is going to impact guidelines based upon its individual results, and this meta-analysis, unfortunately, can't replace such a well-designed, large, controlled, randomized trial."
Lakkireddy anticipated some changes as well. "I hope to see for the next VT guidelines that we should be able to offer VT ablation in appropriate cases as a first-line therapy," he said.
Cell Therapy Shows Safety, Potential For Adults With Ischemic HFrEF, High NT-proBNP
April 17, 2025
4 min read
Add topic to email alerts
Receive an email when new articles are posted on
Please provide your email address to receive an email when new articles are posted on . Subscribe We were unable to process your request. Please try again later. If you continue to have this issue please contact customerservice@slackinc.Com.Back to Healio
Key takeaways:CHICAGO — An autologous point-of-care cell therapy for adults with ischemic HF with reduced ejection fraction was safe and may be beneficial for select candidates, though a pivotal study did not meet its primary efficacy outcome.
New 2-year data from the CardiAMP-HF trial, presented at the American College of Cardiology Scientific Session, suggest that the first cardiac cell therapy utilizing precision medicine may be beneficial for patients with HFrEF with elevated baseline levels of N-terminal pro-B-type natriuretic peptide, who experienced reduced risk for CV death, major adverse CV events and improved quality of life metrics compared with patients who received guideline-directed medical therapy alone. The CardiAMP-HF trial of the autologous bone marrow mononuclear cell therapy (CardiAMP, BioCardia) was stopped early because of slow enrollment and low event rates.
"Cell therapy has been tested in a variety of scenarios, including MI and congestive HF, and in patients with chronic HF, there have been some signals suggesting benefit," Amish N. Raval, MD, FACC, professor of medicine at the University of Wisconsin School of Medicine and Public Health, told Healio. "Among the ischemic HFrEF population, not everyone is the same. Some people carry certain cell populations, such as CD34, that have more favorable properties, and injecting cell therapy in those patients could be beneficial."
Researchers analyzed data from 115 enrolled participants across 18 sites with chronic stable ischemic HFrEF, defined as NYHA class II or III with an EF between 20% and 40% on maximally tolerated guideline-directed medical therapy, whose cells met prespecified cell population thresholds based on previous studies. The mean age of participants was 66 years; 91% were men. Researchers randomly assigned participants to a single dose of cell therapy adjunctive to ongoing medical therapy or to a control sham procedure.
Amish N. Raval
"One of the novelties of this particular trial is you have a prespecified bone marrow assay that can help to identify potential responders," Raval told Healio. "Second, this is easy to implement at the point of care once you identify the patient. It is quick and easy. You are not compromising allergenicity — if a heart transplant does end up being in the patient's future, they're not sensitized by allogeneic cells."
The primary outcome was a hierarchical composite ranking of three tiers of clinical outcomes, analyzed using a win ratio Finkelstein-Schoenfeld analysis method. Tier 1 events were defined as all-cause death, heart transplantation or left ventricular assist device therapy. Tier 2 events included nonfatal HF hospitalizations, MI or stroke. The tier 3 outcome was 6-minute walk test difference from baseline to follow-up.
At 24 months, tier 1 and tier 2 primary efficacy outcomes had more wins for cell therapy compared the sham procedure; however, those wins were negated by a reduction in wins for the change in 6-minute walk test distance, resulting in a win ratio for the primary efficacy outcome of 1.01 (P = .954). There were numerically fewer major adverse CV events among participants in the cell therapy group vs. Controls (20.3% vs. 31.7%), though the number did not reach statistical significance (P = .17).
Raval said there was a stronger trend toward benefit by the primary three-tier composite endpoint among participants with a baseline NT-proBNP of at least 500 pg/mL (P = .07), driven by an 86% relative risk reduction in mortality.
"That population seemed to do much better with the cell treatment vs. The control procedure treatment, with a win ratio of greater than 2," Raval told Healio. "The [major adverse CV event] rates were 17% lower in the cell treatment group vs. The control group. That is compelling and is now the motivation of CardiAMP-HF II trial, which will study the therapy only in this population of high responders."
There were no device-related or procedure-related deaths, strokes or systemic embolisms at 30 days; three participants developed pericardial effusions that were successfully drained, and all completed follow-up through 24 months.
Raval noted that the study protocol for the CardiAMP-HF II trial was redesigned to include the Minnesota Living with Heart Failure Questionnaire as the third-tier outcome in lieu of the 6-minute walk test and restrict enrollment to patients with an NT-proBNP level of at least 500 pg/mL. In a press release, BioCardia announced that the first study sites are now enrolling patients with ischemic HF who meet the new criteria.
"We are making incremental progress," Raval told Healio. "As a field, we have learned so much and it is an exciting time. We are learning about patients who respond [to cell therapy] and who does not. The reality is, we do not have an answer yet regarding who is an ideal candidate for cell therapy. The CardiAMP-HF II trial will shed more light and provide greater insights into this high-responding group to help us answer this question."
Carl J. Pepine
In a press release, Carl J. Pepine, MD, MACC, Eminent Scholar Emeritus and professor in the division of cardiovascular medicine at University of Florida, Gainesville, Chief Medical Editor Emeritus of HealioCardiology Today and co-principal investigator for CardiAMP-HF, said the 2-year data suggest cell therapy may have lasting benefits for the heart that may help prevent disease progression.
"It is an exciting prospect to anticipate an addition to our heart failure armamentarium that can meaningfully improve patients' lives to an extent that many don't enjoy today," Pepine said in the release.
Reference: For more information:Amish N. Raval, MD, FACC, can be reached at anr@medicine.Wisc.Edu.
Perspective Back to Top This type of cell therapy is something patients have been interested in for a long time. CardiAMP-HF had an elegant design. However, this type of study must be conducted with a larger, more diverse population, enriched with patients with elevated NT-proBNP levels. This study enrolled 90% white men. Something was off in the enrollment there, and I hope a larger trial will be more definitive if cell therapy is used in this enriched population. This was a nicely done sham trial, and that is difficult to accomplish. The investigators achieved and even proved with patient surveys that participants did not know which arm of the trial they were in. So, cell therapy looks promising, but I await the results from a larger trial. Mary Norine Walsh, MD, MACC HealioCardiology Today Editorial Board MemberMedical Director, Heart Failure and Cardiac Transplantation ProgramsAscension St. Vincent Heart Center, IndianapolisPast President, American College of CardiologyDisclosures: Walsh reports no relevant financial disclosures.
Sources/DisclosuresCollapse Source: Raval A, et al. Featured clinical research II. Presented at: American College of Cardiology Scientific Session; March 29-31, 2025; Chicago (hybrid meeting).Disclosures: BioCardia sponsored the CardiAMP-HF trial. Raval reports consulting for BioCardia, Blue Rock Therapeutics and Novo Nordisk, serving as co-principal investigator and a member of the steering committee for the CardiAMP-HF trial and holding equity in Cellular Logistics. Pepine reports receiving research funding from BioCardia, Pfizer, Sanofi and XyloCor Therapeutics.
Add topic to email alerts
Receive an email when new articles are posted on
Please provide your email address to receive an email when new articles are posted on . Subscribe We were unable to process your request. Please try again later. If you continue to have this issue please contact customerservice@slackinc.Com.Back to Healio
World's First "nonstop Beating Heart" Transplant Is A Medical Breakthrough
For the first time, surgeons have successfully performed a remarkable new heart transplant in which the donor organ never skips a beat in the process, reducing the damage that can occur during such a complex operation. It ushers in a new era of more successful heart transplant surgery.
A team of surgeons at the National Taiwan University Hospital (NTUH) in Taipei undertook the revolutionary operation, during which the donor heart continues beating between the organ removal and transplantation stages. Traditionally, the donor heart would be removed and preserved in cold storage to reduce its workload – during this stage, it's considered "ischemic time," or the period during which the organ is cut off from blood supply. This comes with the risk of heart damage and rejection once it's transplanted into a recipient.
When the heart is deprived of blood, ischemia – a shortage of oxygen – can damage its muscle tissue, or myocardium, reducing function and health once it is transplanted. While an organ set for transplant rarely endures more than a few hours in ischemic time, it can still lead to myocardial damage.
So the NTUH team skipped this interim, performing the zero-ischemic time transplant that saw the heart continue to beat while between bodies.
"We wanted to perform a heart transplant without any ischemic time so that the heart wouldn't have to stop, and we could also avoid injury that typically occurs after reperfusion," said Chi Nai-hsin, an attending physician from the Cardiovascular Center, during a press conference at the Taipei hospital on Wednesday, April 16.
The NTUH team this week, with the woman (10 from left) who received a new heart via this remarkable surgery last AugustNTUH
The operation was able to be performed thanks to a specially designed organ maintenance system that kept the donor heart pumping with oxygenated blood throughout the process. The NTUH organ care system (OCS) was inspired by extracorporeal membrane oxygenation (ECMO), a type of life support system that supplements heart and lung function.
Hooking the heart up to this OCS, the organ was transported from one operating room to another – without skipping a beat.
As for the patient, the 49-year-old woman with dilated cardiomyopathy was discharged from hospital not long after her surgery last August and is doing well. Subsequent post-operative appointments have shown that the woman maintains a low level of cardiac enzyme – something that spikes in typical transplant conditions, indicating heart muscle injury.
"We have demonstrated the safety and feasibility of the surgery," said Chi, who added that a second successful transplant had been conducted earlier this year.
Overall, NTUH has performed around 700 heart transplant surgeries, but the team hopes that, going forward, more will be using the OCS and skipping ischemic time.
Interestingly, in 2023 and 2024, Stanford University issued papers detailing its own beating-heart transplant operations – but in procedures to date, the hearts had undergone brief periods of ischemic time (10 to 30 minutes) between removal and connecting to the support system.
In both NTUH operations, "the hearts were still beating before procurement, continued beating after procurement, and never stopped – achieving zero ischemic time," said Chen Yih-shurng, head of the hospital's Organ Transplant Team.
The team stated it will continue to refine the procedure and build on organ maintenance technology, so more people can benefit from zero-ischemic-time transplants.
The case study has been accepted for publication in the Journal of Thoracic and Cardiovascular Surgery Techniques, with a pre-proof version available now.
Source: National Taiwan University Hospital
Comments
Post a Comment