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STAT

An MUSC blog
Keyword: cardiology

Cutting Edge-Tools and Team Expertise

Jeffery Winterfield, M.D.Until recently, catheter ablation for ventricular tachycardia (VT) has been a niche subset of clinical cardiac electrophysiology, available in only a few centers nationwide. With top-notch specialists and cutting-edge mapping technology, MUSC Health is on the frontlines of efforts to make VT ablation a more accessible treatment option for patients with ventricular arrhythmia.

Watch a video about ventricular arrhythmia with ablation.

After training under clinical cardiac electrophysiology experts at Harvard Medical School in Boston followed by his first faculty appointment in Chicago at a world-renowned ablation center, MUSC Health Health electrophysiologist Jeffrey R. Winterfield, M.D., was recruited for his experience in treating complex arrhythmias to the MUSC Health Heart & Vascular Center. At MUSC Health, he now serves as director of Ventricular Arrhythmia Service.

Dr. Winterfield explains which patients might benefit from this treatment—and why timing and technology are two key components to ensuring successful outcomes.

Ventricular Arrhythmias: The Right Tools and a Team Approach

Dr. Winterfield says VT ablation procedures, while complex, can be done safely and effectively. The key to success is performing these procedures at a medical center that has the capabilities and the expertise to manage these complex arrhythmias as well as the advanced tools necessary to ensure its safety.

Cutting-edge technology is one way MUSC Health ensures safer VT ablation procedures, says Dr. Winterfield. MUSC Health was chosen as one of only 12 phase 1a sites nationwide to launch an advanced mapping system called Ensite Precision™, recently approved by the FDA.

Traditionally in VT ablation, specialists use mapping technologies to create detailed 3-D anatomic models of the ventricular chamber of interest where an arrhythmia originated. However, that process needed to be done point-by-point and can take up to an hour.

Now, Dr. Winterfield says, the high-density mapping allows him to use a catheter with multiple electrodes to take many points around the ventricular chamber simultaneously.

The result is more precise information, much faster, often in 10 minutes. Not only does that speed up the process, but it’s also made the procedure safer.

Ventricular Arrhythmias: When to Treat With Ablation

Timing is one of the most important factors in determining which ventricular arrhythmias to treat with ablation.

“What we know is that waiting until patients are storming with ventricular arrhythmias is associated with worse outcomes and a higher risk of mortality,” says Dr. Winterfield.

Dr. Winterfield and other researchers at MUSC are investigating multiple aspects of VT ablation, and he agrees that much evidence is still emerging.

What research about VT ablation shows thus far:

  • Earlier is better: Patients fare better with earlier intervention, requiring less frequent hospitalization.
  • Less medication: After VT ablation, there is lower usage of anti-arrhythmic and other complicated medications to treat patients’ arrhythmias.
  • Less hospitalization: It leads to fewer emergency room visits and longer survival overall.

Ventricular Arrhythmias: The Right Candidate

Patients best suited for this treatment include anyone who has undergone treatment for a ventricular arrhythmia through a high-voltage device such as a defibrillator or ventricular pacemaker defibrillator.

Other patients who have had premature ventricular contractions (PVCs) could also be good candidates for ablation, particularly if they’re currently on medication that is either not desired or tolerated well.

In some cases, a high burden of PVCs may exacerbate underlying heart failure. With ablation to reduce or eliminate PVCs, heart failure symptoms and prognosis may improve for some patients.

Research has clearly shown mortality and complications for VT ablation have diminished over the past decade. Dr. Winterfield and others continue to investigate other questions, such as how early VT ablation intervention compares to anti-arrhythmic drug therapy in long-term healthcare costs.

“What we have found in one economic analysis is that healthcare costs are reduced with catheter ablation of ventricular arrhythmia,” says Dr. Winterfield.

Advanced Heart Disease: A Partnership Approach

Dr. Winterfield knows his role as an electrophysiologist is just one facet of managing patients with advanced heart disease, particularly ventricular arrhythmias. Successfully managing these arrhythmias means strong collaboration with referring physicians, especially since some patients travel long distances, sometimes from out of state, for treatment at MUSC Health.

“We're here to help the referring physicians take care of these people who have very difficult problems but carry significant risk for cardiovascular morbidity and mortality,” Dr. Winterfield says. “It is important that we work together to treat them.”

Dr. Winterfield says he keeps the communication lines open and prioritizes calls, emails and questions from referring physicians. He’s certain patients are better off for it.

To reach Dr. Winterfield, email winterfj@musc.edu.

During the past century, cardiopulmonary resuscitative techniques such as CPR and AEDs have moved from the realm of science fiction to the standard of care. Today, we are seeing the same transition with another life-saving technology, extracorporeal membrane oxygenation (ECMO), says Brian Houston, M.D., an assistant professor and medical director of mechanical circulatory support at MUSC Health.

“Today, CPR is a standard of care for both in-hospital and out-of-hospital cardiac arrest. Similarly, automated external defibrillators, or AEDs, are also standard of care for out-of-hospital cardiac arrest. Even 30 years ago, that was science fiction, but now it’s the standard treatment for patients in cardiac arrest,” says Dr. Houston. “I think ECMO is right on the cusp of that transition as well.”

As doctors continue to debate how to best deploy ECMO and which patients would benefit most, one thing is clear: MUSC Health’s ECMO care team is expertly trained to use this technology—quickly, safely and nonsurgically.

What Is ECMO?

It’s helpful to compare ECMO to other cardiopulmonary resuscitation techniques, such as AEDs. An AED is a box designed to deliver electricity to the heart after cardiac arrest and get the heart back into a normal rhythm.

AEDs have been used outside the hospital environment with great success, says Dr. Houston. Multiple public health studies have shown that they:

  • Are cost effective
  • Save lives
  • Contribute to improved out-of-hospital cardiac arrest survival rates

Except AEDs aren’t an effective treatment for all causes of cardiac arrest. Dr. Houston says, “Even if a patient has normal electrical activity or heart rhythm restored, they may not get blood flow back. Their heart may still not be functioning because something other than a heart rhythm problem caused their cardiac arrest.”

In comparison, ECMO is more comprehensive in how it treats cardiac arrest. ECMO takes over the function of the heart and lungs through large tubes, one inserted into a patient’s vein and one into the artery. An ECMO machine pulls blood out through the tube, pumps it back into the body and provides blood flow. This process oxygenates the blood by passing it over a membrane where oxygen is exchanged.

“You can have no lung or heart function, considered a complete cardiac standstill, and still have profusion of all your organs and be alive on an ECMO circuit,” says Dr. Houston.

ECMO was first deployed in 1972, born out of cardiopulmonary bypass technology, a machine that does the work of the heart and lungs during surgery. “Bypass technology is too large to be used long term, and it also has some long-term downsides. ECMO seeks to counteract those drawbacks,” explains Dr. Houston.

An ECMO machine is a small device, which makes it more portable. “The devices are now similar to the size of a lunchbox and can provide a pump and oxygenation device so that they’re more mobile,” says Dr. Houston. “We’re very much on the edge of ECMO technology right now.”

ECMO Benefits: Cardiac Arrest Survival vs. Cost

Compared to a decade ago, ECMO use has risen considerably. “In 2002, there were fewer than 400 cases of ECMO in the United States. In 2009 (the most recent data available), there were greater than 1,600 cases of ECMO use. So it’s more than quadrupled in 7 years, and I suspect those numbers have continued to rise in recent years,” says Dr. Houston.

Its benefits to patients are clear. Quite simply, this technology saves lives. “If you look at out-of-hospital cardiac arrest survival in the United States, it’s less than 8 percent. If someone experiences cardiac arrest on the street or inside their home, they have a less than 8 percent chance of being alive at 1 month.”

In comparison, when patients experiencing cardiac arrest were treated with ECMO, 40 out of 115 people in one study were alive at one year. That’s 35 percent of the participants compared to eight percent. “You’ve saved many more lives using ECMO,” says Dr. Houston.

“I think it’s hard to find any medical intervention that saves that many lives in that dire of a situation,” says Dr. Houston. “However, the flip side is looking at the 70 to 80 people who didn’t survive. They were still treated with ECMO, and ECMO is phenomenally expensive. The cost of any given ECMO run, from start to finish, is more than $300,000.”

Dr. Houston admits that while no doctor likes to think about cost, it’s a realistic piece of the public health conversation on how ECMO can best be implemented. “When we think about how to wisely use this technology as a community, we have to consider cost,” he says.

Another piece of that conversation is who benefits most from this technology. If doctors can better identify the patients who will benefit, the technology can save lives as well as costs.

Dr. Houston believes younger people who have a better chance of recovery might benefit from ECMO more than older patients with more concerning health complications.

Prompt, Expert ECMO Care at MUSC Health

Currently, only specialized ECMO centers can provide ECMO, due to the very intensive care patients require during ECMO treatment. MUSC Health is one such center.

“At MUSC, we have a highly trained group of profusionists and interventional cardiologists who specialize in ECMO,” explains Dr. Houston.

“Whereas in previous years ECMO used to require a surgical procedure, now it’s increasingly done by cardiologists through a catheter-based approach,” he continues. “This allows us to deploy it very rapidly, and our specialized team ensures expert post-deployment care, where we can expertly care for ECMO patients, from start to finish.”

To reach Dr. Houston, email houstobr@musc.edu.
 

Screen Shot of New Medical Video Center

The MUSC Health Medical Video Center is now available online at MUSCHealth.org/medical-video. It profiles cutting-edge surgical procedures and innovative treatments available at MUSC Health and is intended for a health care audience. Its initial areas of focus are cardiology, oncology, neuroscience, and pediatrics. The site contains educational (and explicit) surgical video and photography.

heart made out of rope to represent fibrotic heartIn patients with heart failure with a preserved ejection fraction (HFpEF), the prescribed treatments for managing comorbid hypertension do not seem to improve mortality as they do in other heart failure patients. Now MUSC researchers want to know why. In patients with HFpEF, who account for about half of all heart failure cases, the ventricles gradually thicken and stiffen, preventing normal relaxation from beat to beat. The underlying myocardial changes responsible for HFpEF development have proven elusive, providing a major challenge for cardiologists who seek to treat HFpEF patients. Using a translational approach, MUSC researchers and their colleagues are the first to address this challenge directly.

 MUSC Health cardiologists Michael R. Zile, M.D., and John S. Ikonomidis, M.D., Ph.D., along with their MUSC colleagues Catalin Baicu, Ph.D. and Amy Bradshaw, Ph.D., suspect that changes in certain fibrous proteins contribute to left ventricle relaxation deficits in HFpEF patients. Emerging data from a study led by Zile and published in the April 7, 2015 issue of Circulation1 examined changes in collagen and titin, two major fibrous proteins that constitute the physical scaffold necessary for normal relaxation in the heart. Using small myocardial muscle strips extracted from the hearts of 70 cardiac bypass surgery patients, Zile’s group discovered that a measure of ventricular muscle tension during relaxation, called passive stiffness, was pathologically increased in those patients with HFpEF. Just as suspected, this increase was dependent on changes in both collagen and titin. Importantly, these changes were only detected in patients with both hypertension and HFpEF. Moreover, biomarkers in patient plasma reflecting changes in collagen correlated with the presence and severity of HFpEF.

This work, undertaken at MUSC in collaboration with other centers, is the first to use tissue from HFpEF patients to pinpoint specific changes in titin and collagen as important underlying drivers of HFpEF development. How can this new information be used to help patients? Zile states that MUSC scientists are already collaborating with major pharmaceutical partners to develop new biomarker tools for HFpEF detection. “Proteins and peptides that indicate changes in collagen in the heart can be easily measured in small amounts of blood,” says Zile. “These biomarkers can be used to help make early diagnosis and predict prognostic outcomes in HFpEF patients. The arrival for these novel applications is just over the horizon.”

 Reference

 1Zile MR, et al. Myocardial stiffness in patients with heart failure and a preserved ejection fraction: contributions of collagen and titin. Circulation. 2015 Apr 7;131(14):1247-59.

 

In patients with HFpEF, thicker and stiffer ventricles impair normal relaxation and filling.

 

Genetic Origin of Mitral Valve ProlapseAs part of a multi-center investigation recently reported in the journals Nature1 and Nature Genetics,2 researchers at the Medical University of South Carolina (MUSC) and Harvard/Massachusetts General Hospital as well as other international institutes have discovered genetic and biological causes for MVP. The investigators identify that MVP can be a result of heritable genetic errors that occur during embryonic cardiac development and progress over the lifespan of affected individuals.

Mitral valve prolapse (MVP) affects 1 in 40 individuals making it one of the most prevalent human diseases. Many individuals with MVP develop potentially life-threatening cardiac arrhythmia and heart failure.

In MVP, one or both flaps of the mitral valve bulge backward into the left atrium causing it to close improperly upon termination of atrial systole. Mitral valve prolapse is often detected as a heart murmur and is usually asymptomatic, but in roughly 10% of cases mitral valve regurgitation intensifies to a clinically severe stage. In severe cases, arrhythmic heartbeats develop, which increases the risk of stroke, heart failure and sudden cardiac death. In fact, the risks are high enough in MVP to make it the leading indication for mitral valve surgery.

In the Nature article,1 investigators used linkage analyses and capture sequencing technology to examine protein-coding genes on chromosome 11 in four members of a large family segregating non-syndromic MVP. They discovered a missense mutation in the DCHS1 gene, which codes for the protein dachsous homolog 1, a member of the calcium-dependent cell-cell adhesion family of cadherins. Another DCHS1 mutation was found in additional families segregating deleterious MVP. Both mutations reduce DCHS1 protein stability in mitral valve interstitial cells (MVICs), a finding corroborated with the discovery of the original mutation in MVICs in a human patient with MVP that underwent mitral valve repair surgery. Dchs1 mutant mice displayed similar pathology, along with scattered migration of MVICs during growth, suggesting that protein stability is essential to maintaining cues for cell polarity during mitral valve development.

In a subsequent manuscript published in Nature Genetics,2 the investigators performed a genome-wide association study (GWAS) to identify genetic variants in a population of  more than 10,000 subjects.  Single nucleotide variants (SNPs) with genome-wide significance were identified in the patient cohorts and genes surrounding these SNPs were functionally evaluated in multiple in vivo models. 

The results from both studies highlight a potential unifying biological cause for MVP in the population.

“We have found a genetic and biological reason for one of the most common diseases affecting the human population," says MUSC researcher Russell A. (Chip) Norris, Ph.D., who was a co-senior author on the studies. "This is a critical initial step as we transform this discovery into new remedial therapies to treat the disease.”  Roger R. Markwald, Ph.D.,  and Andy Wessels, Ph.D. both of the Department of Regenerative Medicine and Cell Biology at MUSC, were also co-authors.

If you are interested in supporting medical research, visit donorscure.org, an MUSC-affiliated 501(c)(3) nonprofit organization that allows you to fund biomedical research projects led by researchers across the United States.

References

1 Durst, et al. Mutations in DCHS1 cause mitral valve prolapse. Nature. 2015 Aug 10 [Epub ahead of print]. Available at http://dx.doi.org/10.1038/nature14670

2 Dina C, et al. Genetic association analyses highlight biological pathways underlying mitral valve prolapse.
Nat Genet. 2015 Aug 24.  [Epub ahead of print] Available at http://dx.doi.org/10.1038/ng.3383.

image of patient getting mriImplantable cardioverter-defibrillators (ICDs) and magnetic resonance imaging (MRI) were previously contraindicated, but that is no longer the case thanks to a study (NCT02117414) led by Michael Gold, M.D., Ph.D., Director of the Division of Adult Cardiology at MUSC, the results of which were published in the June 23, 2015 issue of the Journal of the American College of Cardiology. Gold is one of the worldwide principal investigators for the study.

ICDs are used in patients at risk of cardiac arrest (sudden cardiac death); the device is placed underneath the patient’s skin in the upper chest to monitor and stabilize their heartbeat. If the heart beats uncontrollably quickly or abnormally slowly, the device will send a small electrical signal to pace or a larger electrical shock to the heart to normalize the beat.

In the past, physicians were unable to use the most popular method of imaging on patients with ICDs. The magnetic field caused by the MRI could either decrease the overall efficacy of the heart-pacing device, or it could overheat the wires, causing the heart to enter tachyarrhythmia — meaning it was beating too quickly.

The study led by Gold tested the efficacy and safety of an ICD that has a “sleep mode” and that has been modified to protect its internal circuits. This sleep mode is referred to as SureScan (Medtronic; Minneapolis, MN) and disables tachyarrhythmia sensing and defibrillation therapies within the device. It can still monitor the patient’s heartbeat, but the device is temporarily incapable of sending an electric shock to the heart. After placing these novel ICDs under the skin of 275 study participants, researchers conducted either a full-body MRI scan with 1.5T of the chest, cervical, and head regions to ensure maximum radiofrequency exposure up to 2W/kg specific absorption rate (SAR) and gradient field exposure to 200 T/m/s per axis or kept the patient waiting for an hour with no MRI. Researchers then monitored the study participants for adverse changes in their ICD over the next 30 days. The device showed no change in its ability to pace or accurately sense ventricular fibrillation following the scan. The novel ICD was thus deemed to be compatible with MRI. 

sub-cutaneous icd imageThe clinical promise of the subcutaneous implantable cardioverter-defibrillator (S-ICD System®; Boston Scientific, Natick, MA), the first ICD in which the leads are placed under the skin of the chest and are not connected to the heart or vasculature, was confirmed by longer-term (median of 22-month) safety and efficacy data reported in the April 28, 2015 issue of the Journal of the American College of Cardiology (JACC). The S-ICD was approved by the FDA in September 2012 to provide an electric shock to the heart (defibrillation) when the patient’s heart is beating chaotically (ventricular fibrillation) or abnormally fast (ventricular tachyarrhythmia). Because the S-ICD is not implanted in the vasculature or heart, major complications, such as device/lead displacement or failure and pneumothorax, are very rare. Because the S-ICD lacks pacing capacity, it is contraindicated in patients who require a pacemaker or pacing therapy. The JACC article, coauthored by MUSC cardiologist Michael Gold, M.D., Ph.D., is a pooled analysis of 882 patients implanted with the S-ICD who were either participants in the investigational device exemption (IDE) study that led to FDA approval or members of the European EFFORTLESS S-ICD registry, created to evaluate the long-term efficacy and safety of the S-ICD.  Of the 111 events of ventricular fibrillation/tachyarrhythmia reported in the study, 90% (100) were terminated with one shock and 98% (109) within the five shocks available with the S-ICD.  This is similar to reported shock termination rates with traditional ICDs. Device-related complications occurred in 11.1% of patients at three years, with generator pocket infections and inappropriate shocks due to oversensing being the more prominent. Rates of both decreased as providers gained experience with the S-ICD, infection control techniques were implemented, and dual zone programming was favored. The infection rate was reduced more than 3-fold in the latter half of these trials and supraventricular arrhythmias by about 70%. Improvement in this technology will occur in future iterations of the device that should be available in the summer of 2015.  MUSC, the leading center in South Carolina for implantation of this device, participated in many of the early clinical studies that led to the approval of the S-ICD.

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