Ventricular Tachycardia

Computer Simulations May Treat Most Common Heart Rhythm Disorder

Ventricular Tachycardia | Johns Hopkins Medicine

August 19, 2019 — Scientists at Johns Hopkins have successfully created personalized digital replicas of the upper chambers of the heart and used them to guide the precise treatment of patients suffering from persistent irregular heartbeats. These simulations accurately identified where clinicians need to destroy tissue to restore the heart’s normal rhythm.

The proof-of-concept study, published in Nature Biomedical Engineering on August 19,1 is a promising step towards simulation-driven treatments and sets the stage for the team’s U.S. Food and Drug Administration (FDA)-approved clinical trial slated to begin this fall.

“The personalized digital replicas allowed us to accurately simulate and analyze heart electrical activity in 10 patients and determine where tissue needs to be destroyed,” said Natalia Trayanova, the Murray B.

Sachs Professor in the Department of Biomedical Engineering at The Johns Hopkins University Schools of Engineering and Medicine. “The beauty of working with such replicas is that we could test for and predict where irregular heartbeats persist in ways we never could in the clinic.

We ran a mock of the clinical procedure over and over again, until we were sure irregular beats will not re-emerge.”

This approach has the potential to eliminate the process of trial-and-error in treating such heart rhythm disorders and to prevent repeat procedures, said Trayanova.

Atrial fibrillation, or abnormal electrical signals stemming from the heart’s two upper chambers, is the most common cause of irregular heartbeats and affects 1-2 percent of people worldwide. If left untreated, atrial fibrillation can cause fatal strokes.

The typical treatment for the disorder, called catheter ablation, is to thread a catheter emitting radio frequency into the heart to destroy tissue that sends off erratic electrical signals. Specifically, cardiologists will destroy tissue around the atria’s four pulmonary veins, which is where researchers believe the misfiring signals usually begin.

However, a subset of patients with a persistent form of atrial fibrillation and scarring in the atria (fibrosis) do not benefit from receiving standard lesions around the pulmonary veins.

They often have to undergo multiple procedures because abnormal signals keep emerging from new areas of their atria.

With each procedure, new scar tissue forms, which changes the atria’s electrical activity and makes targeting of the misfiring areas that much harder.

The team’s personalized simulation-driven guidance of the ablation procedure, called Optimal Target Identification via Modelling of Arrhythmogenesis (OPTIMA), used contrast-enhanced magnetic resonance imaging (MRI) scans from 10 patients at the Johns Hopkins Hospital to create personalized digital replicas of the diseased atria.

For each personalized model, the team ran initial simulations to predict erratic electrical signals and where tissue should be destroyed. Because each ablation reconfigures the atrial electrical activity and can create new arrhythmias, the researchers performed virtual ablations until no new arrhythmias emerged.

The researchers then took the final ‘map’ of tissue target areas and imported it in the clinical system for catheter navigation.

Physicians then steered the catheter towards not only the tissue that currently causes errant electrical firing, but also towards the tissue that will cause misfiring in the future, as predicted by the simulations.

The entire process, from obtaining an MRI to displaying the final map in the operating room, took less than a week. In the future, Trayanova and the team hope the entire process can be shortened to a day.

While this was a proof-of-concept study meant to demonstrate feasibility and not a clinical trial meant to measure patient outcomes, atrial fibrillation did not recur in any of the patients over the more than 300-day observation period. the 10 patients, only one returned for another ablation, and it was for a simpler atrial arrhythmia.

“I’m very optimistic that this personalized simulation-driven approach will prove to be the missing link needed to markedly improve catheter ablation outcomes in patients with more advanced forms of atrial fibrillation. This new approach may transform current approach to catheter ablation of atrial fibrillation,” added Hugh Calkins, a professor of medicine at Johns Hopkins Medicine and an author on the study.

Watch the VIDEO: Current State of Atrial Fibrillation Ablation Technologies

This study and its success is just one project the Johns Hopkins University Alliance for Cardiovascular Diagnostic and Treatment Innovation (ADVANCE), a center that aims to bring cardiovascular engineering approaches to the clinic, co-directed by Trayanova and Calkins.

“This success is an exciting example of how engineering technology can be used in the clinic to help make treatment more accurate and spare patients from multiple, costly and sometimes risky procedures,” added Trayanova.

For more information:


1. Boyle P.M., Zghaib T., Zahid S., et al. Computationally guided personalized targeted ablation of persistent atrial fibrillation. Nature Biomedical Engineering, published online Aug. 19, 2019.


The NIH/NIGMSCenter for Integrative Biomedical Computing

Ventricular Tachycardia | Johns Hopkins Medicine

Researchers have successfully performed 3D personalized virtual simulations of the heart A 3-D virtual heart.

Credit: Johns Hopkins University In a proof of concept study, scientists at Johns Hopkins report they have successfully performed 3D personalized virtual simulations of the heart to accurately identify where cardiac specialists should electrically destroy cardiac tissue to stop potentially fatal irregular and rapid heartbeats in patients with scarring in the heart. The retrospective analysis of 21 patients and prospective study of five patients with ventricular tachycardia, the researchers say, demonstrate that 3D simulation-guided procedures are worthy of expanded clinical trials.

Results of the study are described in the Sept. 3 issue of Nature Biomedical Engineering.

Credit: Johns Hopkins University

“Cardiac ablation, or the destruction of tissue to stop errant electrical impulses, has been somewhat successful but hampered by a lot of guesswork and variability in the way that physicians figure out which locations to zap with a catheter,” says Natalia Trayanova, Ph.D., the Murray B. Sachs Professor in the Department of Biomedical Engineering at The Johns Hopkins University Schools of Engineering and Medicine. “Our new study results suggest we can remove a lot of the guesswork, standardize treatment and decrease the variability in outcomes, so that patients remain free of arrhythmia in the long term,” she adds.When a normal heart contracts to pump blood throughout the body, a wave of electrical signals flows through the heart, stimulating each cardiac cell to contract—one after the other—in a normal rhythm. After the heart contracts, it relaxes and refills with blood.In people with ventricular tachycardia, the electrical signals in the heart's lower chambers misfire and get stuck within the fist-size organ, crippling the relaxation and refilling process and producing rapid and irregular pulses—or arrhythmias—linked to an estimated 300,000 sudden cardiac deaths in the U.S. each year.Numerous drugs are available to treat and manage so-called infarct-related ventricular tachycardia, but side effects and limitations of the drugs have increased focus on other interventions, especially the potential of cardiac ablation that essentially “rewires” the electrical signaling that gives rise to the arrhythmias. Trayanova says current estimates indicate that cardiac ablation is successful anywhere between 50 and 88 percent of the time, but outcomes are difficult to predict.To perform a traditional ablation, doctors thread a catheter through blood vessels to reach the heart, and use radiofrequency waves to destroy regions in the heart tissue believed to sustain and propagate erratic electrical waves. Mapping of the heart's electrical functioning with a catheter is used to locate ly problem areas, but as Trayanova notes, precise pinpointing of those tissues has been a challenge.In a bid to locate arrhythmias more precisely, Trayanova and her research team developed 3D personalized computational models of patients' hearts contrast-enhanced clinical MRI images. Each heart tissue cell in the model generates electrical signals with the aid of mathematical equations representing how heart cells behave when they are healthy, or when they are semiviable when near the scar. By poking the patient's virtual heart with small electrical signals in different locations, the computer program then determines whether the heart develops an arrhythmia and the location of the tissue that perpetuates it. Using the model, Trayanova then simulates an ablation to that area of the heart and runs the computer program over and over to find multiple locations that doctors should ablate on the actual patient.Among the experiments in the current study, Trayanova and her team used MRI images to create personalized heart models of 21 people who previously had successful cardiac ablation procedures for infarct-related ventricular tachycardia at The Johns Hopkins Hospital between 2006 and 2017. The 3D modeling of these patients correctly identified and predicted the locations where physicians ablated heart tissue. In five patients, the amount of ablated tissue identified by the 3D model was smaller overall—in some cases, more than 10 times smaller—than the area that was destroyed during the patients' procedures.Next, the research team tested the 3D simulation to guide cardiac ablation treatments for three patients with ventricular tachycardia at the University of Utah and two patients at the University of Pennsylvania. Two patients who received the simulation-guided ablation procedure have remained free of tachycardia throughout follow-up periods of 23 and 21 months. One patient who had the simulation procedure remained free of tachycardia after two months of follow up. In two patients, the virtual heart approach predicted that tachycardias would not be inducible — this was confirmed during the clinical procedure, so cardiac ablation was not performed.With this prospective test, the research team demonstrated the feasibility of integrating a computer-simulated prediction into the clinical routine. The patient is scanned approximately 24 hours or less before the procedure. Then, the simulation is created and a prediction is made of where physicians should perform the ablation. Finally, the predicted set of ablation targets is imported into the mapping system before the patient's procedure so that the ablation catheter is navigated directly to the predicted targets.The study represents the first attempt to incorporate personalized simulation predictions as part of anti-arrhythmia treatment. The researchers believe that implementing these predictions will cut down the lengthy and invasive cardiac mapping process and reduce complications experienced by patients. The technology could also reduce the need for repeat procedures through its ability to make the infarcted heart incapable of creating new arrhythmias.”It's an exciting blend of engineering and medicine,” says Trayanova.

“One of the main challenges of catheter ablation is that we are performing procedures on very sick patients with advanced heart disease who have multiple areas in their heart that could sustain arrhythmias,” says Jonathan Chrispin, M.D., Robert E.

Meyerhoff Assistant Professor of Medicine at the Johns Hopkins University School of Medicine, who will lead the clinical trials of this technology. “We are excited to begin testing Trayanova's approach in a prospective clinical trial.

We are hopeful that it can help us achieve our overarching goal of improving quality of life for patients suffering from treatment-resistant ventricular tachycardia.”

Trayanova says the results of a clinical trial are needed to validate the promise of personalized simulation guidance for infarct-related ablation treatments. Further clinical study planned at The Johns Hopkins Hospital was recently approved by the Food and Drug Administration under an investigational device exemption.In addition to Trayanova, other scientists who conducted the experiments and clinical studies and contributed to the research include Adityo Prakosa, Hermenegild Arevalo, Dongdong Deng, Patrick Boyle, Plamen Nikolov, Hiroshi Ashikaga, Carolyn Park, Henry Halperin, Robert Blake III and Jonathan Chrispin from Johns Hopkins; Joshua Blauer, Elyar Ghafoori, Rob MacLeod, Frederick Han and Ravi Ranjan from the University of Utah; and David Callans and Saman Nazarian from the University of Pennsylvania.The research was funded by the National Institutes of Health's Director's Pioneer Award (DP1-HL123271).

Original story appears at Johns Hopkins


Exercise-linked ventricular tachycardia is not a risk to healthy older adults

Ventricular Tachycardia | Johns Hopkins Medicine

Healthy, older adults free of heart disease need not fear that bouts of rapid, irregular heartbeats brought on by vigorous exercise might increase short- or long-term risk of dying or having a heart attack, according to a report by heart experts at Johns Hopkins and the U.S. National Institute on Aging (NIA).

Researchers say such fears surfaced after previous studies found that episodes of errant heart rhythms, more formally known as non-sustained ventricular tachycardia, more than double the chance of sudden death in people who have already suffered a heart attack.

In a study to be presented Nov.

16 at the American Heart Association's (AHA) annual Scientific Sessions in Orlando, the research team monitored for on average 12 years the medical records of 2,234 initially healthy men and women, ages 21 to 96, and participating in the NIA's Baltimore Longitudinal Study of Aging. In adults with no earlier signs of heart disease, researchers found no adverse effects resulting from brief episodes of exercise-induced ventricular tachycardia.

In the study, each volunteer participant had a least one exercise stress test performed before 2001. The test assesses the heart's pumping ability, requiring participants, whose average age at testing was 52, to walk or jog on a treadmill at increasing speeds and inclines until they felt exhausted, about 10 minutes for most.

Eighty-one (roughly 4 percent, 65 men and 16 women, mostly older participants) experienced short periods of rapid, irregular heartbeats during exercise, typically lasting from three to six heartbeats, and at a rate hovering around 175 beats per minute.

Researchers say overall death rates were higher in the tachycardia group than in the nontachycardia group (at 29 percent and 16 percent, respectively).

But when they adjusted their analysis to account for differences in age, gender, and those who developed known risk factors for heart disease early on, they found no measureable increased risk of overall death, death from heart disease, or suffering a heart attack between the tachycardia and nontachycardia groups.

Lead study investigator and cardiologist Joseph Marine, M.D., says the study results should “provide reassurance” among apparently healthy middle-age and older people that such short episodes of ventricular tachycardia provoked on exercise testing do not have long-term consequences to health.

“So long as a medical examination shows no underlying heart disease or other serious health condition, then people should continue to live a normal lifestyle, including a return to exercise after clearance from their physician,” says Marine, an associate professor at the Johns Hopkins University School of Medicine and its Heart and Vascular Institute. “Our results suggest that brief, non-sustained ventricular arrhythmia during exercise testing should, generally, not cause undue alarm in patients or physicians.”

When suspicious about heart disease, Marine says, care providers should investigate further for any signs of ischemia, arterial blockages, heart muscle disease or inherited risk of arrhythmia.

But if everything checks out negative for heart disease, then restrictions on exercise are not needed.

Indeed, he says, regular exercise has long been known to cut down on the risk of developing heart disease.

Study co-investigator and Hopkins cardiologist Gary Gerstenblith, M.D., adds that the latest study results should help physicians better triage which patients to treat after incidents of exercise-induced tachycardia.

“Most people who experience erratic heart rhythms during exercise and who have no underlying heart condition can be left alone, they do not need to be treated, and they can continue to exercise,” says Gerstenblith, a professor at Johns Hopkins School of Medicine.

“However, patients with erratic heartbeats who are later found to have underlying coronary heart disease should refrain from arduous exercise until consulting with their physician about treatment with drugs and/or an implantable device to improve their heart function and to decrease the risk of dying from a potentially fatal heart rhythm.”

Marine says the next steps in their research are to determine whether other arrhythmias brought on by exercise, such as atrial tachycardia, have any impact on future death or heart-attack rates or lead to other arrhythmias.

Funding support for the study was provided by the NIA, a member of the National Institutes of Health.

In addition to Marine and Gerstenblith, Johns Hopkins' Grant Chow, M.D., was involved in this study. Other researchers involved were Veena Shetty, M.S.

, at the Medstar Research Institute; Jeanette Wright and Samer Najjar, M.D., both at the NIA. The senior investigator on the research was Jerome Fleg, M.D.

, at the National Heart, Lung, and Blood Institute, another member of the National Institutes of Health.

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Materials provided by Johns Hopkins Medical Institutions. Note: Content may be edited for style and length.


Catheter ablation of ventricular tachycardia in patients with ARVD/C significantly reduces the burden of ventricular tachycardia

Ventricular Tachycardia | Johns Hopkins Medicine

In Circulation: Arrhythmia and Electrophysiology, Binu Philips (Division of Cardiology, Department of Medicine, The Johns Hopkins Hospital, Baltimore, USA) and co-authors reported that catheter ablation is an important treatment option for the management of ventricular tachycardia in patients with arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVD/C) as, although ventricular tachycardia recurrences are common, the treatment reduces burden of ventricular tachycardia

Philips et al wrote that the aim of their study included determining whether catheter ablation outcomes for ARVD/C have improved with the use of electroanatomic mapping systems and epidcardial ventricular tachycardia ablation and investigating the impact of catheter ablation on the burden of ventricualr tachycardia.

They found, in a matched cohort (for age, 3D mapping technique, repetition of procedure, and centre performing catheter ablation) involving 10 epdicardial procedures and eight endocardial procedures, that ventricular tachycardia free survival was significantly longer with epicardial catheter ablation compared with endocardial catheter ablation (p=0.003). Additionally, ventricular tachycardia free survival was significantly longer in patients in whom 3D electroanatomic mapping system was used for the ablation procedure. Philips et al reported: “Freedom from ventricular tachycardia following a single ablation procedure facilitated by 3D electroanatomical mapping was 50%, 34%, and 24% compared to 36%, 16%, and 8% following a single ablation procedure not facilitated by 3D electroanatomical mapping at one, two, and five years, respectively (p=0.016).“

However, whichever technique was used and whether or not a 3D-electroanatimocal mapping system was used, the rate of ventricular tachycardia reccurrence was high.

Philips et al wrote: “Recurrence of ventricular tachycardia after catheter ablation is not uncommon in ARVD/C and emphasises the fact that catheter ablation cannot be considered to be ‘curative’ in the long term and should not be viewed an alternative to placement of an implantable cardioverter defibrillator.”

Despite the high rate of recurrence of ventricular tachycardia following an ablation procedure, according to Philips et al, catheter ablation should still be “viewed as an important treatment option” for patients with ARVD/C because it reduces ventricular tachycardia burden.

They reported: “The mean frequency of ventricular tachycardia was significantly lower after ventricular tachycardia ablation [0.2±0.4 (median 0.08) ventricular tachycardia episodes/month] as compared with ventricular tachycardia frequency prior to ablation [0.4±0.5 (median 0.

16) ventricular tachycardia episodes/month].” They added that with epicardial catheter ablation, mean ventricular tachycardia burden was reduced from 0.42±0.4 (median 0.2) episodes per month prior to the ablation procedure to 0.05±0.

1 (median 0) episodes per month after the procedure.

Philips et al wrote that catheter ablation was also an important treatment option for patients who “experience intolerant side effects to antiarrhythmic medications or prefer not to take antiarrhythmic medications.

” They added that while epicardial ablation was more efficacious than endocardial procedures, “it should generally be considered after a prior failed endocardial procedure given the higher complication rates associated with pericardial access, mapping, and ablation.”

Harikrishna Tandri, Division of Cardiology, Department of Medicine, Johns Hopkins Hospital, Baltimore, USA, told Cardiac Rhythm News: “The main highlight of our study is that overall the outlook for catheter ablation in ARVD related ventricular tachycardia has significantly improved over the last five years.

This is due to multiple factors including improved understanding of the disease process, use of advanced imaging techniques, substrate based ablation, epicardial ablation approach and improved operator experience with complex ventricular tachycardia ablations.

An initial conservative endocardial ablation is probably appropriate for low volume centres that routinely do not perform epicardial ablations.

However, to achieve best results and to minimise procedural complications, we believe that ARVD patients should be dealt with at high volume ventricular tachycardia ablation centres with particular expertise in epicardial ablation procedures”.


Online Mendelian Inheritance in Man (OMIM)

Ventricular Tachycardia | Johns Hopkins Medicine

A number sign (#) is used with this entry because of the finding that somatic mutation in the gene encoding the G protein subunit alpha-i2 (GNAI1; 139360) is responsible in at least 1 case.

This raises the possibility that familial cases may be caused by mutation in this or related genes.

Stress-induced polymorphic ventricular tachycardia (VTSIP; 604772), also known as catecholaminergic polymorphic ventricular tachycardia, has been found to be caused by mutation in the gene encoding the cardiac ryanodine receptor gene (RYR2; 180902).

Rubin et al. (1992) reported a kindred in which members in 4 successive generations suffered from paroxysmal ventricular tachycardia. They suggested that this is the first report of an autosomal dominant ventricular tachycardia not associated with cardiomyopathy, metabolic disorder, or repolarization abnormality.

In generation 2, 4 of 7 sibs sustained sudden cardiac death. In generation 3, 5 of 10 sibs had documented ventricular tachycardia and 1 of the 5 had sudden cardiac death. In generation 4, 4 of 12 sibs had ventricular tachycardia and 1 of them died suddenly. All the children in generation 5, all prepubertal, were asymptomatic and had normal cardiac investigations.

No systemic abnormalities were found in 2 affected fourth-generation family members studied in great detail. The ventricular tachycardia detected in these sibs on 24-hour ambulatory monitoring had a similar right bundle branch block, with left axis deviation pattern. Rubin et al.

(1992) reviewed the reasons to think that reentry and triggered automaticity were not ly mechanisms, leaving abnormal automaticity as the ly cause.

Familial ventricular tachycardia is usually attributable to recognized conditions such as arrhythmogenic right ventricular dysplasia, hypertrophic cardiomyopathy, familial cardiomyopathy, or one of the long QT syndromes.

There are families with ventricular tachycardia in which no recognized underlying condition has been identified. The features of the disorder are variable from family to family. Fisher et al.

(1999) described a family in which members developed ventricular arrhythmias during sinus tachycardia, whether induced by exercise, isoproterenol infusion, or emotion. Their QT intervals were normal at rest and during exercise. In this family, Fisher et al. (1999) reported a 25-year period of apparently effective medical therapy.

The affected members appeared to have catecholamine hypersensitivity as the basis of their ventricular arrhythmias. Guided therapy using serial exercise-pharmacologic testing provided reliable protection for this familial ventricular arrhythmia.

Idiopathic ventricular tachycardia is a generic term that describes the various forms of ventricular arrhythmias that occur in patients without structural heart disease and in the absence of long QT syndrome.

Many of these tachycardias are focal in origin, localize to the right ventricular outflow tract (RVOT), terminate in response to beta-blockers, verapamil, vagal maneuvers, and adenosine, and are thought to result from cAMP-mediated triggered activity. Lerman et al.

(1998) studied a patient with adrenergically mediated idiopathic RVOT ventricular tachycardia that was unresponsive to adenosine and vagal maneuvers. The subject was a 58-year-old man who developed sustained monomorphic ventricular tachycardia during an intense argument. Because of insensitivity of the tachycardia to adenosine, Lerman et al.

(1998) investigated the possibility that a mutation in the inhibitory branch of the cAMP signal transduction pathway could have elevated intracellular cAMP and facilitated the spontaneous initiation of ventricular tachycardia. They succeeded in identifying a point mutation in the GNAI2 gene (139360.0004) from the arrhythmogenic focus biopsied in this patient.

Both stable and transient transfection of CHO-K1 cells with the mutant gene showed that this mutation increased the stimulated levels of cAMP and prevented adenosine suppression of cAMP. No mutations were detected in myocardial tissue sampled from regions remote from the origin of the tachycardia, or in peripheral lymphocytes.