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AHA, ACC Change in Requirement for Surgical Support for PCI Performance: Class IIb -> Class III, Level of Evidence A: Support Nonemergent PCI without Surgical Backup (Change of class IIb, Level of evidence B).


AHA, ACC Change in Requirement for Surgical Support:  Class IIb -> Class III, Level of Evidence A: Supports Nonemergent PCI without Surgical Backup (Change of class IIb, Level of Evidence B).

Larry H Bernstein, MD, FCAP, Author, Curator, Volumes 1,2,3,4,5,6 Co-Editor and Author, Volume Two & Five, Co-Editor and Justin Pearlman, MD, PhD, FACC, Content Consultant to Six-Volume e-SERIES A: Cardiovascular Diseases

 

Voice of content consultant: Justin Pearlman, MD, PhD, FACC

The American Heart Association (AHA) and the American College of Cardiology (ACC) have convened teams of experts to summarize evidence and opinion regarding a wide range of decisions relevant to cardiovascular disease. The system accounts for some of the short comings of “evidence based medicine” by allowing for expert opinion in areas where evidence is not sufficient. The main argument for evidence-based medicine is the existence of surprises, where a plausible decision does not actually appear to work as desired when it is tested. A major problem with adhesion to evidence based medicine is that it can impede adaptation to individual needs (we are all genetically and socially/environmentally unique) and impede innovation. Large studies carry statistical weight but do not necessary consider all relevant factors. Commonly, the AFFIRM trial is interpreted as support that rate control suffices for most atrial fibrillation (AFIB), but half of those randomized to rhythm control were taken off anticoagulation without teaching patients to check their pulse daily for recurrence of AFIB. Thus the endorsed “evidence” may have more to do with the benefits of anticoagulation for both persisting and recurring AFIB and rhythm control may yet prove better than rate control. However, with wide acceptance of a particular conclusion, randomizing to another treatment may be deemed unethical, or may simply not get a large trial due to lack of economic incentive, leaving only the large trial products as the endorsed options. A medication without patent protection, such as bismuth salts for H Pylori infection, lacks financial backing for large trials.

The American Heart Association Evidence-Based Scoring System
Classification of Recommendations

● Class I: Conditions for which there is evidence, general

agreement, or both that a given procedure or treatment is

useful and effective.

● Class II: Conditions for which there is conflicting evidence,

a divergence of opinion, or both about the usefulness/

efficacy of a procedure or treatment.

● Class IIa: Weight of evidence/opinion is in favor of

usefulness/efficacy.

● Class IIb: Usefulness/efficacy is less well established by

evidence/opinion.

● Class III: Conditions for which there is evidence, general

agreement, or both that the procedure/treatment is not useful/

effective and in some cases may be harmful.

Level of Evidence

● Level of Evidence A: Data derived from multiple randomized

clinical trials

● Level of Evidence B: Data derived from a single randomized

trial or nonrandomized studies

● Level of Evidence C: Consensus opinion of experts

Circulation 2006 114: 1761 – 1791.

Assessment of Coronary Artery Disease by Cardiac Computed Tomography

A Scientific Statement From the American Heart Association Committee on Cardiovascular Imaging and Intervention, Council on Cardiovascular Radiology and Intervention, and Committee on Cardiac Imaging, Council on Clinical Cardiology

Reported by Chris Kaiser, Cardiology Editor, MedPage  7/2013  

 

Action Points

  1. Patients with indications for nonemergency PCI who presented at hospitals without on-site cardiac surgery, were randomly assigned to undergo PCI at a hospital without on-site cardiac surgery or at a hospital with on-site cardiac surgery.
  2. The rates of death, myocardial infarction, repeat revascularization, and stroke did not differ significantly between the groups.
  3. Community hospitals without surgical services can safely perform percutaneous coronary intervention (PCI) in low-risk patients — and not refuse higher-risk patients either, the MASS COMM trial found.

Summary

  • The co-primary endpoint of major adverse cardiac events (MACE) at 30 days occurred at a rate of 9.5% in the 10 hospitals without surgical backup versus 9.4% in the seven hospitals with onsite surgery (P<0.001 for noninferiority), Alice K. Jacobs, MD, of Boston University School of Medicine, and colleagues found.
  • The other co-primary endpoint of MACE at 12 months was also significant, occurring in 17.3% of patients in hospitals without backup versus 17.8% in centers with surgical services (P<0.001 for non-inferiority), they reported in the study published online by the New England Journal of Medicine. The findings were also reported at the American College of Cardiology meeting.

Study Characteristics and Results

Primary Endpoints

  1. death
  2. myocardial infarction
  3. repeat revascularization
  4. stroke
no significant differences between the two groups at 30 days and at 12 months.

Rate of stent thrombosis at 30 days

similar in both groups (0.6% versus 0.8%) and at 12 months (1.1% versus 2.1%).
Jacobs and colleagues noted that the 2011 PCI guidelines lacked evidence to fully support nonemergent PCI without surgical backup (class IIb, level of evidence B).

CPORT – E trial

Even though those guidelines came out before the results of the CPORT-E trial were published, CPORT-E trial showed similar non-inferiority at 9 months between centers that perform PCI with or without surgical backup in a cohort of nearly 19,000 non-emergent patients. The CPORT-E results were published in the March 2012 issue of the New England Journal of Medicine, and in May three cardiology organizations published an update to cath lab standards allowing for PCI without surgical.

 MASS COMM study

To further the evidence, Jacobs and colleagues in 2006  had designed and carried out the Randomized Trial to Compare Percutaneous Coronary Intervention between Massachusetts Hospitals with Cardiac Surgery On-Site and Community Hospitals without Cardiac Surgery On-Site (MASS COMM) in collaboration with the Massachusetts Department of Public Health who collaborated to obtain “evidence on which to base regulatory policy decisions about performing non-emergent PCI in hospitals without on-site cardiac surgery.”

  • Hospitals without backup surgery were required to perform at least 300 diagnostic catheterizations per year, and operators were mandated to have performed a minimum of 75 PCI procedures per year.
  • The researchers randomized 3,691 patients to each arm in a 3:1 ratio (without/with backup). The median follow-up was about 1 year.
  • The median age of patients was 64, one-third were women, and 92% were white. Both groups had similar median ejection fractions at baseline (55%).
  • The mean number of vessels treated was 1.17 and most patients (84%) had one vessel treated. The mean number of lesions treated was 1.45 and most patients (67%) had one lesion treated.

The indications for PCI were:

1. ST-segment elevated MI (>72 hours before PCI of infarct-related or non–infarct-related artery — 19% and 17%
2. Unstable angina — 45% and 47%
3. Stable angina — 27% and 28%
4. Silent ischemia — 5% and 6%
5. Other — 2.5% and 2.8%
Regarding secondary endpoints, both groups had similar rates of emergency CABG and urgent or emergent PCI at 30 days. Results at 30 days and 12 months were similar for rates of ischemia-driven target-vessel revascularization and target-lesion revascularization. Other endpoints as well were similar at both time points, including
  • all-cause death
  • repeat revascularization
  • stroke
  • definite or probable stent thrombosis
  • major vascular complications
Researchers adjusted for a 1.3 greater chance of MACE occurring at a randomly selected hospital compared with another randomly selected hospital and found
  • the relative risks at 30 days and 12 months “were consistent with those of the primary results” (RR 1.02 and 0.98, respectively).

However, they cautioned that new sites perhaps should be monitored as they gain experience.

A prespecified angiographic review of 376 patients who were in the PCI-without-backup arm and 87 in the other arm showed no differences in
  1. rates of procedural success,
  2. proportion with complete revascularization, or
  3. the proportion of guideline-indicated appropriate lesions for PCI.
Such results show consistent practice patterns between the groups, they noted.
The study had several limitations including the
  • loss of data for 13% of patients, the
  • exclusion of some patients for certain clinical and anatomical features, and
  • not having the power to detect non-inferiority in the separate components of the primary endpoint, researchers wrote.

Cardio Notes: Score Predicts PCI Readmission

Published: Jul 15, 2013

By Chris Kaiser, Cardiology Editor, MedPage Today
  

A simple calculation of patient variables before PCI may help stem the tide of readmission within the first month. Also this week, two blood pressure drugs that benefit diabetics and imaging cardiac sympathetic innervation.

Pre-PCI Factors Predict Return Trip

A new 30-day readmission risk prediction model for patients undergoing percutaneous coronary intervention (PCI) showed it’s possible to predict risk using only variables known before PCI, according to a study published online in Circulation: Cardiovascular Quality and Outcomes.

After multivariable adjustment, the 10 pre-PCI variables that predicted 30-day readmission were older age (mean age 68 in this study), female sex, insurance type (Medicare, state, or unknown), GFR category (less than 30 and 30-60 mL/min per 1.73m2), current or history of heart failure, chronic lung disease, peripheral vascular disease, cardiogenic shock at presentation, admit source (acute and non-acute care facility or emergency department), and previous coronary artery bypass graft surgery.

Additional significant variables post-discharge that predicted 30-day readmission were beta-blocker prescribed at discharge, post-PCI vascular or bleeding complications, discharge location, African American race, diabetes status and modality of treatment, any drug-eluting stent during the index procedure, and extended length of stay.

A risk score calculator using the pre-PCI variables will be available online soon, according to Robert W. Yeh, MD, MSc, of Massachusetts General Hospital in Boston, and colleagues.

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Reporter: Prabodh Kandala, PhD.

Zebrafish, popular as aquarium fish, now have an important place in research labs as a model organism for studying human diseases.

At the 2012 International Zebrafish Development Conference, held June 20-24 in Madison, Wisconsin, numerous presentations highlighted the utility of the zebrafish for examining the basic biological mechanisms underlying human disorders and identifying potential treatment approaches for an impressive array of organ and systemic diseases.

Inflammatory Bowel Disease

Inflammatory bowel disease (IBD), while rarely fatal, can have a substantial negative impact on an individual’s quality of life due to abdominal pain, diarrhea, vomiting, bleeding, and severe cramps. The causes of this chronic inflammatory disorder are largely unknown and existing treatments, usually anti-inflammatory drugs, are often not effective. In addition, IBD is often associated with increased risk of developing intestinal cancer.

Researchers from the University of Pittsburgh are using zebrafish to study the biological mechanisms that lead to intestinal inflammation, as often seen in IBD, providing additional understanding that may allow development of better therapies. Prakash Thakur, a research associate working with Nathan Bahary, M.D., Ph.D., described a mutant zebrafish strain that shows many pathological characteristics similar to IBD, including inflammation, abnormal villous architecture, disorganized epithelial cells, increased bacterial growth and high numbers of dying cells in the intestine. “Most of the hallmark features of the disease are seen in this mutant. We are utilizing this fish as a tool to unravel fundamental mechanisms of intestinal pathologies that may contribute to intestinal inflammatory disorders, ” Mr. Thakur said.

The fish have a genetic mutation that disrupts de novo synthesis of an important signaling molecule called phosphatidylinositol (PI). The lack of de novo PI synthesis, Mr. Thakur and his colleagues found, leads to chronic levels of cellular stress, particularly the endoplasmic reticum stress and, ultimately, inflammation. Drugs or other interventions targeting the cellular stress response pathway, rather than just inflammation, helped restore a healthy intestinal structure and increase cell survival in the fish intestine, suggesting this mechanism as a potential therapeutic target for patients with inflammatory disorders, including IBD.

Doxorubicin-Induced Heart Failure

Doxorubicin is a potent chemotherapy drug used to treat many types of cancer, including leukemia, lymphoma, carcinoma, soft tissue sarcoma, and bladder, breast, lung, stomach and ovarian cancers. Unfortunately, drug-induced cardiomyopathy is a common side effect and can lead to heart failure in cancer patients, not only during treatment, but months or years later.

“We hope to identify some drug which only blocks the side effect of doxorubicin but preserves the therapeutic effect,” said Yan Liu, Ph.D., a postdoctoral researcher working in Dr. Randall Peterson’s lab at the Massachusetts General Hospital.

Dr. Liu developed a zebrafish model of doxorubicin-induced cardiomyopathy. The fish experience heart failure within two days of treatment with symptoms similar to those seen in humans, including fewer heart muscle cells, ventricular collapse, and ineffective heartbeats.

The researchers used the model to screen through thousands of potential drug compounds and identified two — visnagin and diphenylurea — that both improved cardiac function and reduced doxorubicin-induced cell death in the heart. Importantly, both compounds specifically protected heart tissue, but not tumor cells, from the toxic effects of doxorubicin. Both seem to act through the suppression of a particular signaling pathway, the c-Jun N-terminal kinase pathway, in the heart cells but not tumor cells.

Dr. Liu also reported promising preliminary results with mice showing reduced cell death and improved cardiac function, indicating that these compounds may also be active in mammals and giving hope for therapies that specifically treat doxorubicin’s side effects without negating its anti-tumor activity.

Spinal Muscular Atrophy

Spinal muscular atrophy (SMA) is a group of progressive neurodegenerative diseases that affect the nerves in the spinal cord that control muscles, leading to weakness, movement difficulties, poor posture, and trouble breathing and eating.

SMA is linked to mutations in a specific motor neuron survival gene, SMN1. Though mouse studies have reported immature and ineffective synaptic connections between motor neurons and muscles, little is known about the molecular mechanisms leading to those problems or how they might be fixed.

Graduate student Kelvin See, working with Associate Professor Christoph Winkler, Ph.D., at the National University of Singapore used zebrafish with activity-sensitive fluorescence to provide a visual readout of motor neuron activation. They confirmed that low SMN1 levels are associated with low neuronal influx of calcium ions, which play a critical role in triggering neurotransmitter release and thus stimulating the muscles. With their zebrafish model, Mr. See and Dr. Winkler also identified another gene with a similar effect, neurexin, which is important in synaptic structure but had never been implicated in SMA.

In a surprise discovery, the researchers found they could use the same sensor to see activation of a neighboring cell type called Schwann cells. “This gives us the unique opportunity to look at the role of SMN1 not just in motor neurons but also in the surrounding tissue,” said Mr. See.

They saw reduced excitability in Schwann cells also, suggesting that a full understanding of SMA will require a broader view of the affected cell populations. Their results provide several new insights into the fundamental processes disrupted in SMA.

Acute T-cell Lymphoblastic Leukemia and Lymphoma (T-ALL/T-LBL)

Human acute T-cell lymphoblastic leukemias (ALL) and lymphomas (LBL) have high relapse rates in pediatric patients and high mortality rates in adults. Hui Feng, M.D., Ph.D., currently at the Pharmacology Department and Center for Cancer Research at Boston University School of Medicine, is using a zebrafish model of leukemia to search for promising targets for new molecular treatments for these diseases.

To date, studies have identified several biological pathways involved in ALL and LBL, all with a known oncogene in common called c-Myc. However, Myc is so common, involved in regulating more than 15 percent of all genes, that it is very hard to study.

“Because this is a huge list of downstream targets, it is very challenging to predict which genes in the pathway to target to treat Myc-related cancers,” said Dr. Feng.

In work performed in collaboration with Thomas Look, M.D., at the Dana-Farber Cancer Institute, Dr. Feng is combining the power of zebrafish genetics with human clinical studies to hone in on potential genes of interest.

Using a fish strain that reliably develops T-cell lymphoma by two months of age, they identified a novel gene called DLST that is involved in metabolism and energy production in cells. Evidence from human cancer cell lines and patients indicate that abnormally high levels of the protein may be involved in the human disease as well.

Reducing DLST activity in the fish significantly delayed tumor progression and growth, suggesting it is a promising target for developing new therapies for ALL and LBL.

Ref:

http://www.sciencedaily.com/releases/2012/07/120706184348.htm

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