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Keyword: heart

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.”


 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.


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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