• FAME II: FFR-guided PCI reduces urgent reinterventions, but not change mortality, MI
  [Imaging > Imaging; Aug 28, 2012]
• DeFACTO results encouraging for “virtual” FFR despite missing target
  [Imaging > Imaging; Aug 26, 2012]
• CT-based FFR saves money by reducing unnecessary PCIs
  [Imaging > Imaging; Jul 24, 2012]
• Echo vs nuclear for stress imaging after revascularization 
  [Imaging > Imaging; Jul 06, 2012]
• Stress echo in asymptomatic patients after revascularization “not worth it” 
  [Imaging > Imaging; May 14, 2012]

“I think it’s a potential game-changer, because for the first time you have the ability to look at coronary stenosis and ischemia simultaneously, [and] you have the ability to pinpoint the lesion that is causing the ischemia,” DISCOVER FLOW senior investigator Dr James Min (Cedars-Sinai Medical Center, Los Angeles, CA) told heartwire. “You can imagine a scenario where somebody has an abnormal stress test and then you go in and you do an angiogram and see four or five stenoses, but you don’t really know which one caused the ischemia.” But this new “virtual fractional flow reserve” process—or FFRCT—can quantify the fractional flow reserve for each lesion with the data taken from a CCTA, thereby revealing which stenoses are causing ischemia and ought to be treated, as well as which stenoses do not need to be treated. “We’ve never before had this one-stop shop to . . . pinpoint the lesions that cause the ischemia noninvasively.”

As reported by heartwire at EuroPCR 2011, in DISCOVER FLOW, Dr Bon-Kwon Koo (Seoul National University Hospital, Korea) and colleagues used computation of FFRCT to assess 159 vessels in 103 patients undergoing CCTA. Results of the study are published in the November 1, 2011 issue of the Journal of the American College of Cardiology.

All of the patients also underwent invasive CCTA and invasive catheter FFR imaging. Ischemia was defined as an FFR of <0.80 and anatomically obstructive coronary disease was defined as stenosis >50% as measured on the CCTA scan. The diagnostic performance of FFRCT and CCTA were assessed against invasive FFR as the reference standard. Of the patients in the study, 56% had at least one vessel with an FFR of <0.80.

Because only about half of stenoses over 50% actually cause ischemia, the specificity of traditional assessment of a stenosis by CCTA is below 50%. “The concern there is that you identify some high-grade stenoses that are angiographically confirmed, but the lesions don’t actually cause ischemia.” Fractional flow reserve measures how much of the blood flow is being blocked by a lesion, so it is about 25% more accurate than traditional CCTA at picking out lesions that cause ischemia, Min explained.

Per vessel diagnostic accuracy FFRCT and CCTA (reference for both was invasive FFR) 

a. Ischemic defined as <0.80

b. Ischemia defined as stenosis >50%

FFRCT can assess stenoses from any CCTA scan—prospectively gated or retrospectively gated—without any additional imaging techniques or changes to the acquisition parameters. Just as computational fluid dynamics can predict the behavior of an airplane wing under different environmental parameters, FFRCT can measure the flow of blood through a stenotic coronary based on the specific geometry of the patient’s coronaries and myocardium.

At the American Heart Association meeting in Orlando next month, Min will present results of a substudy from DISCOVER FLOW looking specifically at intermediate-grade stenoses (40%-69%), which present the most difficult treatment decisions. “If somebody sees a 90% stenosis or 10% stenosis, they are comfortable with what to do with that. But when you hit that 40% to 70% range—it’s possible that those lesions are ischemic, but you don’t know until you actually assess them,” Min said.

DISCOVER FLOW was designed to evaluate the accuracy of FFRCT on a per-vessel basis, but the more important demonstration of its value will be its ability to guide treatment decisions for each patient. TheDEFACTO trial, which finished enrollment at 17 centers about three weeks ago, is evaluating FFRCT per patient. “That’s the big one,” Min said. “DEFACTO will be the pivotal trial.” Specifically, the 285-patient DEFACTO trial is assessing the ability of CCTA plus FFRCT to determine the presence or absence of at least one hemodynamically significant coronary stenosis in each trial subject. Invasive catheter FFR is the reference standard. Min expects that study to be completed in the first quarter of 2012.

http://www.theheart.org/article/1299631.do

• Dr James Min leaves Cornell for Cedars-Sinai
  [heartwire > Murmurs; Aug 25, 2011]
• Multivessel PCI during STEMI associated with higher short- and long-term mortality
  [Acute Coronary Syndromes > Acute coronary syndromes; Aug 05, 2011]
• Adding function to CTA with “noninvasive FFR” ups accuracy, may cut procedures: DISCOVER FLOW
  [Imaging > Imaging; May 18, 2011]
• ROMICAT: More on prognostic value of CCTA, but larger trials still required 
  [Imaging > Imaging; May 12, 2011]
• Two-year FAME results published: Durable benefit of FFR
  [Interventional/Surgery > Interventional/Surgery; May 26, 2010]

1. Budoff MJ. Emerging Clinical applications for cardiac CT. Society of Cardiovascular Computed Tomography 2013 Annual Scientific Meeting; July 12, 2013; Montreal, QC.
2. Min JK. The future of cardiac CT. What will the next 12 months bring? Society of Cardiovascular Computed Tomography 2013 Annual Scientific Meeting; July 12, 2013; Montreal, QC.

Related links

• 1-mSv radiation dose for clinical coronary CT: “We’re there” 
  [Imaging > Imaging; Jul 15, 2013]
• CT prior to TAVR helps reduce paravalvular leak, other complications
  [Imaging > Imaging; Jul 15, 2013]
• CORE320: CT can do work of SPECT and an angiogram
  [Imaging > Imaging; Aug 28, 2012]
• Noninvasive fractional flow reserve CT could dramatically change angiography
  [Imaging > Imaging; Oct 24, 2011]

SOURCE

http://www.theheart.org/article/1561163.do?utm_medium=email&utm_source=20130717_heartwire&utm_campaign=newsletter

IV. Stress CT Perfusion matches SPECT for detecting Myocardial Ischemia

Montreal, QC – In stress testing using regadenoson (Lexiscan, Astellas), detection rates of myocardial ischemia were similar with less invasive computed-tomography (CT) perfusion imaging compared with the reference method, single-photon-emission CT (SPECT) imaging, in a phase 2 trial [1].

JULY 18, 2013 Marlene Busko

Regadenoson, a selective adenosine-receptor agonist that produces coronary vasodilation in patients unable to undergo exercise stress testing, is the most common agent used to induce pharmaceutical stress in SPECT tests in the US; it was used off-label for the CT imaging.

Dr Ricardo C Cury (Baptist Hospital of Miami, FL) presented the trial results here at a late-breaking clinical-trials session at the Society of Cardiovascular Computed Tomography (SCCT) 2013 Scientific Meeting.

To heartwire, Cury noted that this trial established noninferiority of regadenoson stress CT perfusion to the reference method, regadenoson SPECT, to detect or exclude myocardial ischemia, which was the primary study outcome.

“This is the second multicenter trial validating [regadenoson] stress CT perfusion, which [builds on the accumulating supporting data from] many single-center studies,” he said, adding that it is still too early, however, to implement these findings into clinical practice.

To heartwire, session moderator Dr John Hoe (Parkway Health Radiology, Singapore) commented that “this is quite an important multicenter trial . . . and the results look very good.” Echoing Cury, he added that “this [research] is slowly [progressing] along the path to validate [regadenoson] CT perfusion as a technique to assess myocardial ischemia.”

In study, 39% of patients had suspected CAD

This was a crossover study conducted at 11 sites in the US, using six types of CT scanners, including 64-, 128-, 256-, and 320-slice machines.

A total of 124 individuals with known (39%) or suspected CAD were randomized to either rest and stress SPECT using regadenoson on day 1, followed by rest and combined stress CT perfusion using regadenoson and coronary CT angiography on day 2; or the same tests in the reverse order.

At baseline, the subjects had a mean age of about 62 and an average body-mass index (BMI) of close to 30. Their average heart rate increased from 64 to 84 beats per minute with the stress-CT perfusion test.

Myocardial ischemia was defined as having two or more reversible defects.

High agreement, specificity, and sensitivity

When it came to detecting myocardial ischemia, CT perfusion imaging agreed with the findings of the reference method, SPECT, 87% of the time (95% CI 0.77-0.97).

“This was well above the specified primary end point for the agreement rate between SPECT and CT perfusion for the detection of ischemia,” Cury said.

Stress CT perfusion imaging also had a high specificity (84%) and sensitivity (90%) for detecting or excluding myocardial ischemia.

Similarly, when it came to detecting the presence or absence of one or more fixed myocardial defects, CT perfusion imaging agreed with the results of the reference method, SPECT, 86% of the time (95% CI 0.74-0.98).

Again, stress CT perfusion imaging had a high specificity (95%) and sensitivity (77%) for detecting or excluding fixed defects.

Used alone, compared with the reference standard of SPECT, stress CT perfusion diagnosed or excluded ischemia accurately in 85% of cases, whereas CT angiography alone made the correct diagnosis in 69% of cases. Thus, “stress CT perfusion may add significant [diagnostic] value to CT angiography alone,” Cury noted.

Regadenoson was well tolerated, and the most common adverse events were flushing or headache.

SOURCE

http://www.theheart.org/article/1561685.do

V. New Protocol Limits Use Of SPECT MPI For Angina

Article Date: 07 May 2013 – 1:00 PDT

A new stress test protocol that investigates reducing the use of perfusion imaging in low risk patients undergoing SPECT myocardial perfusion imaging for possible anginasymptoms was found to be diagnostically safe, revealed a US retrospective analysis. The study, reported as an abstract¹ at the International Conference on Nuclear Cardiology and Cardiac CT (ICNC11) May 5 to May 8 in Berlin, Germany, predicted that using exercise ECG stress testing alone in patients with high exercise capacity would have had no adverse effects on their prognosis at five years.

“Our results are reassuring in that there are few patients whose diagnosis of coronary artery disease (CAD) would be missed,” said Milena Henzlova, the first author of the study. “Not only would widespread adoption of this approach reduce radiation exposure, it would also save considerable amounts of time and money.”

Single-photon emission computed tomography (SPECT) myocardial perfusion imaging (MPI) has been used for over 30 years to detect ischemia in patients with suspected CAD. In SPECT MPI patients are injected with radioactive agents (such as Tc-99m or Thallium 201) whose passage through the heart is viewed with a SPECT camera. By comparing the heart’s blood flow at rest and during stress (patients exercise on a treadmill, cycle ergometers or undergo pharmacological stress with vasodilators or dobutamine), cardiologists can determine if the myocardium receives sufficient blood supply, as well as the location and extent of underlying CAD.

“Because it’s non invasive and many patients with a chest pain syndrome don’t have coronary disease, SPECT MPI is often viewed as a ‘gate keeper’ to coronary angiography,” explained Lane Duvall, an investigator in the study.

While SPECT MPI represents a well established technique, the main disadvantage is that patients are exposed to diagnostic levels of radiation. In recent years intensive efforts have been made to reduce ionizing radiation associated with cardiac imaging due to concerns that it damages DNA in cells and may ultimately give rise to cancer. Indeed, extrapolating data from the survivors of the Hiroshima and Nagasaki atomic bombs, Andrew Einstein, from Columbia University Medical Center, New York, has estimated that the low levels of radiation encountered during medical imaging might lead to a 2% excess relative risk for future cancers.

Other studies have suggested that exercise treadmill testing alone may be sufficient to predict CVD outcome without use of SPECT MPI in low risk patients. In 2011, Bourque and colleagues from the University of Virginia, Charlottesville, reported that patients who exercise at >10 metabolic equivalents (METS), [the unit used to estimate the amount of oxygen used by the body during physical activity] during stress testing had a very low prevalence of significant ischemia and very low rates of cardiac events during follow-up².

The advantage of exercise treadmill testing is that it offers a quicker study that involves no radiation exposure, with prognostic information provided via a variety of treadmill scores, most notably the Duke Treadmill score. “This has led to investigators questioning the added value of SPECT MPI over exercise testing alone. There’s growing recognition that patients need to be treated as individuals and that those in whom the CVD risks are considered negligible shouldn’t be undergoing the risks of radiation exposure,” said Duvall.

In the current abstract, Henzlova, Duvall and colleagues, from the Mount Sinai School of Medicine, New York, US, set out to investigate retrospectively if a provisional injection protocol in which patients where they met certain criteria were converted to exercise treadmill tests without imaging maintained diagnostic accuracy and prognostic ability. For the retrospective study, data was reviewed from a total of 24,689 patients who had undergone SPECT MPI between February 2004 and June 2010. After exclusion of patients older than 65 years of age, who had known CAD and uninterruptable resting ECGs, 5,352 subjects were identified for analysis.

Subjects were divided into those who would have met all the criteria for not undergoing SPECT MPI (the No injection group n= 1,561 [29.2%]) and those who met the criteria for undergoing SPECT MPI (the Yes injection group, n=3,791, [70.8%]). For the study the criteria laid down for patients considered eligible for not undergoing SPECT MPI included achieving a maximal predicted heart rate >85%, > 10 METs of exercise, no symptoms of chest pain or significant shortness of breath during stress, and no ECG changes (ST depression or arrhythmia). Outcomes for the two groups at five years were then compared based on their actual myocardial perfusion imaging results and all-cause mortality that had been retrospectively identified from the National Death Index.

At a mean follow-up of 60.6 months, 1.1% of patients had died in the No-injection cohort compared to 2.2% Yes injection cohort (P=.01). Furthermore perfusion results were abnormal in 5.9% of the No injection group compared to 14.4% in the Yes injection group (P<.0001). The risk adjusted survival at the end of the follow up was 98.8% in the No injection group compared to 97.2% for patients found to have normal perfusion in the Yes injection group (P=0.009).

“Withholding isotope injections in these selected patients was found to be diagnostically safe with a small percentage of ‘missed’ abnormal perfusion studies, a very low rate of significant stress perfusion defects and left ventricular ischemia, and a prognosis which was better than their counterparts who were injected with the isotope,” said Duvall.

Eliminating the need for imaging in 6% of the 9 million SPECT MPI studies performed annually in the US, the authors added, would result in significant cost savings and the total test time would be halved from three hours to roughly one hour. “There’s a need to accept that less can be more. By individualizing therapy we can reduce radiation exposure and costs without jeopardizing the quality, the diagnostic utility or missing something important,” said Henzlova. 

VI. Contemporary Stress Echo good for Risk Stratification in Chest-Pain Units

12/20/2012, Lisa Nainggolan

London, UK – Doctors in a London chest-pain unit have shown that employing contemporary stress echocardiography in patients with suspected acute coronary syndrome (ACS) but normal ECG and negative troponin is a successful approach for risk stratification [1].

Stress echo is feasible and safe and allows early triage and rapid discharge of patients, plus it is a good predictor of hard events, say Dr Benoy N Shah (Royal Brompton Hospital, London, UK) and colleagues in their paper published online December 18, 2012 in Circulation: Cardiovascular Imaging. Those with an abnormal stress echo had a 13- to15-fold increased risk of MI or death compared with those who had a normal stress echo, they report.

“Stress echo is a very effective gatekeeper for patients undergoing further risk stratification,” senior author Dr Roxy Senior (Royal Brompton Hospital) told heartwire. “It helps select patients for coronary angiography [those with a positive stress echo] and allows immediate discharge of those patients with a negative result.”

Stress echo is perceived to be a technique that is difficult, but that is a misconception.

But Senior says his chest-pain unit is the only one in the UK using this approach. “It is perceived to be a technique that is difficult, but that is a misconception. We have nine stress-echo operators, and it’s easy to train people. With contemporary techniques, which employ contrast in around 50% of cases, the images are quite clear and quick and easy to interpret. It’s very user-friendly. We want to show people around the world that it’s a very doable technique, so why don’t you use it?”

Stress echo also compares favorably with other tests used or proposed for risk stratification of such patients, he says. Exercise ECG is perhaps the most basic technique, “and we have shown that the downstream costs are lower with stress echo than with exercise ECG,” given that the latter provides such equivocal results [2], he explained. And with regard to other imaging modalities that have been employed in this way, computed tomography coronary angiography (CTCA) and single-photon-emission computed tomography (SPECT) require the use of ionizing radiation and have other drawbacks, he notes.

Nevertheless, he and his colleagues say that further, multicenter studies comparing stress echo with CTCA, SPECT, and other imaging techniques for this purpose “will help determine the most cost-effective means of investigating this acute patient population.”

Stress echo performed within 24 hours of admission

Shah and colleagues say that after they showed in 2007 that stress echo was more cost-effective than exercise ECG, they have been employing the former in day-to-day practice in their unit to assess patients who come in with severe chest pain, but whose troponin is negative at 12 hours and whose ECG is “nondiagnostic” (ie, does not suggest any abnormality or shows only minor changes).

The current study is a retrospective look at the patients they have seen so far and is the first evaluation of the clinical impact of incorporating stress echo in a real-world chest-pain unit for the assessment of both short- and long-term prediction of hard events, they say.

“This was sort of an audit; we wanted to know, ‘Is this right? Or are we overcalling it?’ ” Senior explains.

He says the stress echos are performed, for the most part, “within 24 hours” of admission to the chest-pain unit, from 9 am-5 pm Monday to Friday. Those admitted on a weekend will wait slightly longer for a stress echo, he acknowledged. The stress echo is performed on a treadmill if the patient is capable of exercise; if not, a pharmacological stress test is performed using dobutamine. Approximately 30% of the patients in this study performed the test on a treadmill, Senior noted.

Results of the stress echo are available quickly and, if negative, the patient is discharged immediately. If they are positive, the patient is investigated further.

Event rate much higher for those with a positive stress echo

In the study, 839 consecutive patients were assessed; 802 were available for follow-up. Approximately 75% of them had a normal stress echo and were discharged.

“The 30-day readmission rate for all patients was extremely low,” Senior notes, but for those with a negative stress echo it was exceedingly low (at 0.3% compared with 1.1% for those with an abnormal stress echo).

A normal stress echo carried a 99.7% event-free survival for death and 99.5% event-free survival for all hard events in the first year of follow-up; these event rates increased 15-fold and 13-fold respectively if the stress echo was abnormal.

There were 15 “hard” events, 0.5% in the normal stress echo group and 6.6% in the abnormal stress echo group in the first year. At two years, 2.3% of those in the normal stress echo group had died or had a nonfatal MI compared with 9.6% in the stress echo abnormal group, and at three years these figures were 5.1% and 21.1%, respectively. The median follow-up for the study was 27 months.

“For the patients who had a positive stress echo, the event rate was much higher,” Senior notes. Of these 184 patients, 98 had ischemia and most of these underwent coronary angiography, with 57 demonstrating flow-limiting coronary artery disease and 30 subsequently undergoing revascularization.

Among all prognostic variables, only abnormal stress echo (hazard ratio 4.08) and advancing age (HR 1.78) predicted hard events in multivariable regression analysis.

Stress echo should be much more widely used in chest-pain units

“This study demonstrates the excellent feasibility and safety of stress echo in a real-world chest-pain-unit setting, with rapid early triaging and discharge and accurate risk stratification,” the researchers say.

“The two most important outcomes for patients reassured and discharged from the emergency department are that they do not suffer early mortality or early readmission with the same complaint. Our study highlights the excellent negative predictive value of stress echo and very low 30-day readmission rate.”

In addition, the results show that stress echo “appropriately influences the use of coronary angiography and subsequent revascularization” and overall support the wider use of this technique in chest-pain units, they conclude.

Senior has previously received consultancy fees from Lantheus Medical. The coauthors report they have no conflicts of interest.

Other related articles published on this Open Access Online Scientific Journal, include the following:

Fractional Flow Reserve (FFR) & Instantaneous wave-free ratio (iFR): An Evaluation of Catheterization Lab Tools for Ischemic Assessment

Justin D Pearlman, MD, PhD, FACC and Aviva Lev-Ari, PhD, RN

http://pharmaceuticalintelligence.com/2013/07/04/fractional-flow-reserve-ffr-instantaneous-wave-free-rario-ifr-an-evaluation-of-catheterization-lab-tools-for-ischemic-assessment/

CT Angiography (CCTA) Reduced Medical Resource Utilization compared to Standard Care reported in JACC

Aviva Lev-Ari, PhD, RN

http://pharmaceuticalintelligence.com/2013/05/16/ct-angiography-ccta-reduced-medical-resource-utilization-compared-to-standard-care-reported-in-jacc/

Acute Chest Pain/ER Admission: Three Emerging Alternatives to Angiography and PCI – Corus CAD, hs cTn, CCTA

Curator: Aviva Lev-Ari, PhD, RN

http://pharmaceuticalintelligence.com/2013/03/10/acute-chest-painer-admission-three-emerging-alternatives-to-angiography-and-pci/

Acute and Chronic Myocardial Infarction: Quantification of Myocardial Perfusion Viability – FDG-PET/MRI vs. MRI or PET alone

Justin D. Pearlman, MD, PhD and Aviva Lev-Ari, PhD, RN

http://pharmaceuticalintelligence.com/2013/05/22/acute-and-chronic-myocardial-infarction-quantification-of-myocardial-viability-fdg-petmri-vs-mri-or-pet-alone/