Feeds:
Posts
Comments

Posts Tagged ‘Cedars-Sinai Medical Center’


LDL, HDL, TG, ApoA1 and ApoB: Genetic Loci Associated With Plasma Concentration of these Biomarkers – A Genome-Wide Analysis With Replication

Reporter: Aviva Lev-Ari, PhD, RN

Genetic Loci Associated With Plasma Concentration of Low-Density Lipoprotein Cholesterol, High-Density Lipoprotein Cholesterol, Triglycerides, Apolipoprotein A1, and Apolipoprotein B Among 6382 White Women in Genome-Wide Analysis With Replication

Daniel I. Chasman, PhD*Guillaume Paré, MD, MS*Robert Y.L. Zee, PhD, MPH, Alex N. Parker, PhD, Nancy R. Cook, ScD, Julie E. Buring, ScD, David J. Kwiatkowski, MD, PhD, Lynda M. Rose, MS, Joshua D. Smith, BS, Paul T. Williams, PhD, Mark J. Rieder, PhD, Jerome I. Rotter, MD, Deborah A. Nickerson, PhD, Ronald M. Krauss, MD,Joseph P. Miletich, MD and Paul M Ridker, MD, MPH

Author Affiliations

From the Center for Cardiovascular Disease Prevention (D.I.C., G.P., R.Y.L.Z., N.R.C., J.E.B., L.M.R., P.M.R.) and Donald W. Reynolds Center for Cardiovascular Research (D.I.C., G.P., R.Y.L.Z., N.R.C., D.J.K., P.M.R.), Brigham and Women’s Hospital, Harvard Medical School, Boston, Mass; Amgen, Inc, Cambridge, Mass (A.N.P., J.M.P.); Department of Genome Sciences, University of Washington, Seattle, Wash (J.D.S., M.J.R., D.A.N.); Life Science Division, Lawrence Berkeley National Laboratory, Berkeley, Calif (P.T.W., R.M.K.); Medical Genetics Institute, Cedars-Sinai Medical Center, Los Angeles, Calif (J.I.R.); and Children’s Hospital Oakland Research Institute, Oakland, Calif (R.M.K.).

Correspondence to Daniel I. Chasman, Center for Cardiovascular Disease Prevention, Brigham and Women’s Hospital, 900 Commonwealth Ave E, Boston, MA 02215. E-mail dchasman@rics.bwh.harvard.edu

Abstract

Background— Genome-wide genetic association analysis represents an opportunity for a comprehensive survey of the genes governing lipid metabolism, potentially revealing new insights or even therapeutic strategies for cardiovascular disease and related metabolic disorders.

Methods and Results— We have performed large-scale, genome-wide genetic analysis among 6382 white women with replication in 2 cohorts of 970 additional white men and women for associations between common single-nucleotide polymorphisms and low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, triglycerides, apolipoprotein (Apo) A1, and ApoB. Genome-wide associations (P<5×10−8) were found at the PCSK9 gene, the APOB gene, the LPLgene, the APOA1-APOA5 locus, the LIPC gene, the CETP gene, the LDLR gene, and the APOE locus. In addition, genome-wide associations with triglycerides at the GCKRgene confirm and extend emerging links between glucose and lipid metabolism. Still other genome-wide associations at the 1p13.3 locus are consistent with emerging biological properties for a region of the genome, possibly related to the SORT1 gene. Below genome-wide significance, our study provides confirmatory evidence for associations at 5 novel loci with low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, or triglycerides reported recently in separate genome-wide association studies. The total proportion of variance explained by common variation at the genome-wide candidate loci ranges from 4.3% for triglycerides to 12.6% for ApoB.

Conclusion— Genome-wide associations at the GCKR gene and near the SORT1gene, as well as confirmatory associations at 5 additional novel loci, suggest emerging biological pathways for lipid metabolism among white women.

 SOURCE:

Circulation: Cardiovascular Genetics.2008; 1: 21-30

doi: 10.1161/ CIRCGENETICS.108.773168

Read Full Post »


Heart and Aging Research in Genomic Epidemiology: 1700 MIs and 2300 coronary heart disease events among about 29 000 eligible patients: Design of Prospective Meta-Analyses of Genome-Wide Association Studies From 5 Cohorts

Reporter: Aviva Lev-Ari, PhD, RN

 

Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) Consortium

Heart and Aging Research in Genomic Epidemiology: 1700 MIs and 2300 coronary heart disease events among about 29 000 eligible patients: Design of Prospective Meta-Analyses of Genome-Wide Association Studies From 5 Cohorts

Bruce M. Psaty, MD, PhD, Christopher J. O’Donnell, MD, MPH, Vilmundur Gudnason, MD, PhD, Kathryn L. Lunetta, PhD, Aaron R. Folsom, MD, Jerome I. Rotter, MD,André G. Uitterlinden, PhD, Tamara B. Harris, MD, Jacqueline C.M. Witteman, PhD,Eric Boerwinkle, PhD and on Behalf of the CHARGE Consortium

Author Affiliations

From the Cardiovascular Health Research Unit, Departments of Medicine, Epidemiology, and Health Services (B.M.P.), University of Wash; Center for Health Studies, Group Health (B.M.P.), Seattle, Wash; the National Heart, Lung and Blood Institute and the Framingham Heart Study (C.J.O.D.), Framingham, Mass; Icelandic Heart Association and the Department of Cardiovascular Genetics (Y.G.), University of Iceland, Reykjavik, Iceland; Department of Biostatistics (K.L.), Boston University School of Public Health, Mass; Division of Epidemiology and Community Health (A.R.F.), University of Minnesota, Minneapolis; Medical Genetics Institute (J.I.R.), Cedars-Sinai Medical Center, Los Angeles, Calif; Departments of Internal Medicine (A.G.U.) and Epidemiology (A.G.U., J.C.M.W.), Erasmus Medical Center, Rotterdam, The Netherlands; Laboratory of Epidemiology, Demography, and Biometry (T.B.H.), Intramural Research Program, National Institute on Aging, Bethesda, Md; and Human Genetics Center and Division of Epidemiology (E.B.), University of Texas, Houston.

Guest editor for this article was Elizabeth R. Hauser, PhD.

Abstract

Background— The primary aim of genome-wide association studies is to identify novel genetic loci associated with interindividual variation in the levels of risk factors, the degree of subclinical disease, or the risk of clinical disease. The requirement for large sample sizes and the importance of replication have served as powerful incentives for scientific collaboration.

Methods— The Cohorts for Heart and Aging Research in Genomic Epidemiology Consortium was formed to facilitate genome-wide association studies meta-analyses and replication opportunities among multiple large population-based cohort studies, which collect data in a standardized fashion and represent the preferred method for estimating disease incidence. The design of the Cohorts for Heart and Aging Research in Genomic Epidemiology Consortium includes 5 prospective cohort studies from the United States and Europe: the Age, Gene/Environment Susceptibility—Reykjavik Study, the Atherosclerosis Risk in Communities Study, the Cardiovascular Health Study, the Framingham Heart Study, and the Rotterdam Study. With genome-wide data on a total of about 38 000 individuals, these cohort studies have a large number of health-related phenotypes measured in similar ways. For each harmonized trait, within-cohort genome-wide association study analyses are combined by meta-analysis. A prospective meta-analysis of data from all 5 cohorts, with a properly selected level of genome-wide statistical significance, is a powerful approach to finding genuine phenotypic associations with novel genetic loci.

Conclusions— The Cohorts for Heart and Aging Research in Genomic Epidemiology Consortium and collaborating non-member studies or consortia provide an excellent framework for the identification of the genetic determinants of risk factors, subclinical-disease measures, and clinical events.

Example of Coronary Heart Disease

The cohort-study methods papers provide detail about many of the phenotypes listed in Table 2. For coronary heart disease, investigators knowledgeable about the phenotype in each study decided to focus on fatal and nonfatal myocardial infarction (MI) as the primary outcome because the MI criteria differed in only trivial ways among the studies. There were some minor differences in the definition of the composite outcome of MI, fatal coronary heart disease, and sudden death, which became the secondary outcome. Only subjects at risk for an incident event were included in the analysis. MI survivors whose DNA was drawn after the event were not eligible. The primary analysis was restricted to Europeans or European Americans. Patients entered the analysis at the time of the DNA blood draw, and were followed until an event, death, loss to follow up, or the last visit. The main recommendations of the Analysis Committee were adopted, and a threshold of 5×10−8 was selected for genome-wide statistical significance. Analyses in progress include about 1700 MIs and 2300 coronary heart disease events among about 29 000 eligible patients. Each cohort conducted its own analysis, and results were uploaded to a secure share site for the fixed-effects meta-analysis. Even with this number of events (Supplemental Figure 2), power is good for only for relatively high minor allele frequencies (>0.25) and large relative risks (>1.3).

The authors had full access to and take full responsibility for the integrity of the data. All authors have read and agree to the manuscript as written.

Discussion

In thousands of published papers, the 5 CHARGE cohort studies and many of the collaborating studies have already characterized the risk factors for and the incidence and prognosis of a variety of aging-related and cardiovascular conditions. The analysis of the incident MI, for instance, is free from the survival bias typically associated with cross-sectional or case-control studies. The methodologic advantages of the prospective population-based cohort design, the similarity of phenotypes across 5 studies, the availability of genome-wide genotyping data in each cohort, and the need for large sample sizes to provide reliable estimates of genotype-phenotype associations have served as the primary incentives for the formation of the CHARGE consortium, which includes GWAS data on about 38 000 individuals. The consortium effort relies on collaborative methods that are similar to those used by the individual contributing cohorts.

Phenotype experts who know the studies and the data well are responsible for phenotype-standardization across cohorts. The coordinated prospectively planned meta-analyses of CHARGE provide results that are virtually identical to a cohort-adjusted pooled analysis of individual level data. This approach–the within-study analysis followed by a between-study meta-analysis–avoids the human subjects issues associated with individual-level data sharing.

Editors, reviewers, and readers expect replication as the standard in science.6 The finding of a genetic association in one population with evidence for replication in multiple independent populations provides moderate assurance against false-positive reports and helps to establish the validity of the original finding. In a single experiment, the discovery-replication structure is traditionally embodied in a 2-stage design. The CHARGE consortium includes up to 5 independent replicate samples as well as additional collaborating studies for some phenotype working groups, so that it would have been possible to set up analysis plans within CHARGE to mimic the traditional 2-stage design for replication. For instance, the 2 largest cohorts could have served as the discovery set and the others as the replication set. However, attaining the extremely small probability values expected in GWAS requires large sample sizes. For any phenotype, a prospective meta-analysis of all participating cohorts, with a properly selected level of genome-wide statistical significance to minimize the chance of false-positives, is the most powerful approach to finding new genuine associations for genetic loci.25 When findings narrowly miss the prespecified significance threshold, genotyping individuals in other independent populations provides additional evidence about the association. For findings that substantially exceed pre-established significance thresholds, the results of a CHARGE meta-analysis effectively provide evidence of a multistudy replication.

The effort to assemble and manage the CHARGE consortium has provided some interesting and unanticipated challenges. Participating cohorts often had relationships with outside study groups that predated the formation of CHARGE. Timelines for genotyping and imputation have shifted. Purchases of new computer systems for the volume of work were sometimes necessary. Each cohort came to the consortium with their own traditions for methods of analysis, organization, and authorship policies that, while appropriate for their own work, were not always optimal for collaboration with multiple external groups. Within each cohort, the investigators had often formed working groups that divided up the large number of available phenotypes in ways that made sense locally but did not necessarily match the configuration that had been adopted by other cohorts. The Research Steering Committee has attempted to create a set of CHARGE working groups that accommodate the needs and the conventions of the various cohorts. Transparency, disclosure, and professional collaborative behavior by all participating investigators have been essential to the process.

Resource limitations are another challenge. Grant applications that funded the original single-study genome-wide genotyping effort typically imagined a much simpler design. The CHS whole-genome study had as its primary aim, for instance, the analysis of data on 3 endpoints, coronary disease, stroke and heart failure. With a score of active phenotype working groups, the CHARGE collaboration broadened the scope of the short-term work well beyond initial expectations for all the participating cohorts.

One of the premier challenges has been communications among scores of investigators at a dozen sites. CHS and ARIC are themselves multi-site studies. To be successful, the CHARGE collaboration has required effective communications: (1) within each cohort; (2) between cohorts; (3) within the CHARGE working groups; and (4) among the major CHARGE committees. In addition to the traditional methods of conference calls and email, the CHARGE “wiki,” set up by Dr J. Bis (Seattle, Wash), has provided a crucial and highly functional user-driven website for calendars, minutes, guidelines, working group analysis plans, manuscript proposals, and other documents. In the end, there is no substitute for face-to-face meetings, especially at the beginning of the collaboration, and this complex meta-organization has benefited from several CHARGE-wide meetings.

The major emerging opportunity is the collaboration with other studies and consortia. Many working groups have already incorporated nonmember studies into their efforts. Several working groups have coordinated submissions of initial manuscripts with the parallel submission of manuscripts from other studies or consortia. Several working groups have embarked on plans for joint meta-analyses between CHARGE and other consortia. CHARGE has tried to acknowledge and reward the efforts of champions, who assume leadership responsibility for moving these large complex projects forward and who are often hard-working young investigators, the key to the future success of population science.

The CHARGE Consortium represents an innovative model of collaborative research conducted by research teams that know well the strengths, the limitations, and the data from 5 prospective population-based cohort studies. By leveraging the dense genotyping, deep phenotyping and the diverse expertise, prospective meta-analyses are underway to identify and replicate the major common genetic determinants of risk factors, measures of subclinical disease, and clinical events for cardiovascular disease and aging.

SOURCE:

Circulation: Cardiovascular Genetics.2009; 2: 73-80

doi: 10.1161/ CIRCGENETICS.108.829747

 

Read Full Post »


Atherosclerosis Risk and Highly Sensitive Cardiac Troponin-T Levels in European Americans and Blacks: Genome-Wide Variation Association Study

Reporter: Aviva Lev-Ari, PhD, RN

Association of Genome-Wide Variation With Highly Sensitive Cardiac Troponin-T Levels in European Americans and Blacks

A Meta-Analysis From Atherosclerosis Risk in Communities and Cardiovascular Health Studies

Bing Yu, MD, MSc, Maja Barbalic, PhD, Ariel Brautbar, MD, Vijay Nambi, MD, Ron C. Hoogeveen, PhD, Weihong Tang, PhD, Thomas H. Mosley, PhD, Jerome I. Rotter, MD,Christopher R. deFilippi, MD, Christopher J. O’Donnell, MD, Sekar Kathiresan, MD,Ken Rice, PhD, Susan R. Heckbert, MD, PhD, Christie M. Ballantyne, MD, Bruce M. Psaty, MD, PhD and Eric Boerwinkle, PhD on behalf of the CARDIoGRAM Consortium

Author Affiliations

From the Human Genetic Center, University of Texas Health Science Center at Houston, Houston, TX (B.Y., M.B., E.B.); Deptartment of Medicine (A.B., V.N., R.C.H., C.M.B.), and Human Genome Sequencing Center (E.B.), Baylor College of Medicine, Houston, TX; Department of Epidemiology, University of Minnesota, Minneapolis, MN (W.T.); Division of Geriatrics, University of Mississippi Medical Center, Jackson, MS (T.H.M.); Medical Genetics Institute, Cedars-Sinai Medical Center, Los Angeles, CA (J.I.R.); School of Medicine, University of Maryland, Baltimore, MD (C.R.D.); National Heart, Lung, and Blood Institute and Framingham Heart Study, National Institutes of Health, Bethesda, MD (C.J.O.D.); Center for Human Genetic Research & Cardiovascular Research Center, Massachusetts General Hospital and Department of Medicine, Harvard Medical School, Boston, MA (S.K.); Department of Biostatistics (K.R.), and Cardiovascular Health Research Unit & Department of Epidemiology (S.R.H.), University of Washington, Seattle, WA; and Cardiovascular Health Research Unit, Departments of Medicine, Epidemiology, and Health Services, University of Washington & Group Health Research Institute, Group Health Cooperative, Seattle, WA (B.M.P.).

Correspondence to Eric Boerwinkle, PhD, Human Genetic Center, University of Texas School of Public Health, 1200 Herman Pressler E-447, Houston, TX 77030. E-mailEric.Boerwinkle@uth.tmc.edu

Abstract

Background—High levels of cardiac troponin T, measured by a highly sensitive assay (hs-cTnT), are strongly associated with incident coronary heart disease and heart failure. To date, no large-scale genome-wide association study of hs-cTnT has been reported. We sought to identify novel genetic variants that are associated with hs-cTnT levels.

Methods and Results—We performed a genome-wide association in 9491 European Americans and 2053 blacks free of coronary heart disease and heart failure from 2 prospective cohorts: the Atherosclerosis Risk in Communities Study and the Cardiovascular Health Study. Genome-wide association studies were conducted in each study and race stratum. Fixed-effect meta-analyses combined the results of linear regression from 2 cohorts within each race stratum and then across race strata to produce overall estimates and probability values. The meta-analysis identified a significant association at chromosome 8q13 (rs10091374;P=9.06×10−9) near the nuclear receptor coactivator 2 (NCOA2) gene. Overexpression of NCOA2 can be detected in myoblasts. An additional analysis using logistic regression and the clinically motivated 99th percentile cut point detected a significant association at 1q32 (rs12564445; P=4.73×10−8) in the gene TNNT2, which encodes the cardiac troponin T protein itself. The hs-cTnT-associated single-nucleotide polymorphisms were not associated with coronary heart disease in a large case-control study, but rs12564445 was significantly associated with incident heart failure in Atherosclerosis Risk in Communities Study European Americans (hazard ratio=1.16; P=0.004).

Conclusions—We identified 2 loci, near NCOA2 and in the TNNT2 gene, at which variation was significantly associated with hs-cTnT levels. Further use of the new assay should enable replication of these results.

SOURCE:

Circulation: Cardiovascular Genetics.2013; 6: 82-88

Published online before print December 16, 2012,

doi: 10.1161/ CIRCGENETICS.112.963058

Read Full Post »


Comorbidity of Diabetes and Aging in Cardiovascular Diseases

Reporter: Aviva Lev-Ari, PhD, RN

Heart and Aging Research in Genomic Epidemiology1700 MIs and 2300 coronary heart disease events among about 29 000 eligible patients

Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) ConsortiumDesign of Prospective Meta-Analyses of Genome-Wide Association Studies From 5 Cohorts

Bruce M. Psaty, MD, PhD, Christopher J. O’Donnell, MD, MPH, Vilmundur Gudnason, MD, PhD, Kathryn L. Lunetta, PhD, Aaron R. Folsom, MD, Jerome I. Rotter, MD, André G. Uitterlinden, PhD, Tamara B. Harris, MD, Jacqueline C.M. Witteman, PhD, Eric Boerwinkle, PhD and on Behalf of the CHARGE Consortium

Author Affiliations

From the Cardiovascular Health Research Unit, Departments of Medicine, Epidemiology, and Health Services (B.M.P.), University of Wash; Center for Health Studies, Group Health (B.M.P.), Seattle, Wash; the National Heart, Lung and Blood Institute and the Framingham Heart Study (C.J.O.D.), Framingham, Mass; Icelandic Heart Association and the Department of Cardiovascular Genetics (Y.G.), University of Iceland, Reykjavik, Iceland; Department of Biostatistics (K.L.), Boston University School of Public Health, Mass; Division of Epidemiology and Community Health (A.R.F.), University of Minnesota, Minneapolis; Medical Genetics Institute (J.I.R.), Cedars-Sinai Medical Center, Los Angeles, Calif; Departments of Internal Medicine (A.G.U.) and Epidemiology (A.G.U., J.C.M.W.), Erasmus Medical Center, Rotterdam, The Netherlands; Laboratory of Epidemiology, Demography, and Biometry (T.B.H.), Intramural Research Program, National Institute on Aging, Bethesda, Md; and Human Genetics Center and Division of Epidemiology (E.B.), University of Texas, Houston.

Guest editor for this article was Elizabeth R. Hauser, PhD.

Abstract

Background— The primary aim of genome-wide association studies is to identify novel genetic loci associated with interindividual variation in the levels of risk factors, the degree of subclinical disease, or the risk of clinical disease. The requirement for large sample sizes and the importance of replication have served as powerful incentives for scientific collaboration.

Methods— The Cohorts for Heart and Aging Research in Genomic Epidemiology Consortium was formed to facilitate genome-wide association studies meta-analyses and replication opportunities among multiple large population-based cohort studies, which collect data in a standardized fashion and represent the preferred method for estimating disease incidence. The design of the Cohorts for Heart and Aging Research in Genomic Epidemiology Consortium includes 5 prospective cohort studies from the United States and Europe: the Age, Gene/Environment Susceptibility—Reykjavik Study, the Atherosclerosis Risk in Communities Study, the Cardiovascular Health Study, the Framingham Heart Study, and the Rotterdam Study. With genome-wide data on a total of about 38 000 individuals, these cohort studies have a large number of health-related phenotypes measured in similar ways. For each harmonized trait, within-cohort genome-wide association study analyses are combined by meta-analysis. A prospective meta-analysis of data from all 5 cohorts, with a properly selected level of genome-wide statistical significance, is a powerful approach to finding genuine phenotypic associations with novel genetic loci.

Conclusions— The Cohorts for Heart and Aging Research in Genomic Epidemiology Consortium and collaborating non-member studies or consortia provide an excellent framework for the identification of the genetic determinants of risk factors, subclinical-disease measures, and clinical events.

Example of Coronary Heart Disease

The cohort-study methods papers provide detail about many of the phenotypes listed in Table 2. For coronary heart disease, investigators knowledgeable about the phenotype in each study decided to focus on fatal and nonfatal myocardial infarction (MI) as the primary outcome because the MI criteria differed in only trivial ways among the studies. There were some minor differences in the definition of the composite outcome of MI, fatal coronary heart disease, and sudden death, which became the secondary outcome. Only subjects at risk for an incident event were included in the analysis. MI survivors whose DNA was drawn after the event were not eligible. The primary analysis was restricted to Europeans or European Americans. Patients entered the analysis at the time of the DNA blood draw, and were followed until an event, death, loss to follow up, or the last visit. The main recommendations of the Analysis Committee were adopted, and a threshold of 5×108 was selected for genome-wide statistical significance. Analyses in progress include about 1700 MIs and 2300 coronary heart disease events among about 29 000 eligible patients. Each cohort conducted its own analysis, and results were uploaded to a secure share site for the fixed-effects meta-analysis. Even with this number of events (Supplemental Figure 2), power is good for only for relatively high minor allele frequencies (>0.25) and large relative risks (>1.3).

The authors had full access to and take full responsibility for the integrity of the data. All authors have read and agree to the manuscript as written.

Discussion

In thousands of published papers, the 5 CHARGE cohort studies and many of the collaborating studies have already characterized the risk factors for and the incidence and prognosis of a variety of aging-related and cardiovascular conditions. The analysis of the incident MI, for instance, is free from the survival bias typically associated with cross-sectional or case-control studies. The methodologic advantages of the prospective population-based cohort design, the similarity of phenotypes across 5 studies, the availability of genome-wide genotyping data in each cohort, and the need for large sample sizes to provide reliable estimates of genotype-phenotype associations have served as the primary incentives for the formation of the CHARGE consortium, which includes GWAS data on about 38 000 individuals. The consortium effort relies on collaborative methods that are similar to those used by the individual contributing cohorts.

Phenotype experts who know the studies and the data well are responsible for phenotype-standardization across cohorts. The coordinated prospectively planned meta-analyses of CHARGE provide results that are virtually identical to a cohort-adjusted pooled analysis of individual level data. This approach–the within-study analysis followed by a between-study meta-analysis–avoids the human subjects issues associated with individual-level data sharing.

Editors, reviewers, and readers expect replication as the standard in science.6 The finding of a genetic association in one population with evidence for replication in multiple independent populations provides moderate assurance against false-positive reports and helps to establish the validity of the original finding. In a single experiment, the discovery-replication structure is traditionally embodied in a 2-stage design. The CHARGE consortium includes up to 5 independent replicate samples as well as additional collaborating studies for some phenotype working groups, so that it would have been possible to set up analysis plans within CHARGE to mimic the traditional 2-stage design for replication. For instance, the 2 largest cohorts could have served as the discovery set and the others as the replication set. However, attaining the extremely small probability values expected in GWAS requires large sample sizes. For any phenotype, a prospective meta-analysis of all participating cohorts, with a properly selected level of genome-wide statistical significance to minimize the chance of false-positives, is the most powerful approach to finding new genuine associations for genetic loci.25 When findings narrowly miss the prespecified significance threshold, genotyping individuals in other independent populations provides additional evidence about the association. For findings that substantially exceed pre-established significance thresholds, the results of a CHARGE meta-analysis effectively provide evidence of a multistudy replication.

The effort to assemble and manage the CHARGE consortium has provided some interesting and unanticipated challenges. Participating cohorts often had relationships with outside study groups that predated the formation of CHARGE. Timelines for genotyping and imputation have shifted. Purchases of new computer systems for the volume of work were sometimes necessary. Each cohort came to the consortium with their own traditions for methods of analysis, organization, and authorship policies that, while appropriate for their own work, were not always optimal for collaboration with multiple external groups. Within each cohort, the investigators had often formed working groups that divided up the large number of available phenotypes in ways that made sense locally but did not necessarily match the configuration that had been adopted by other cohorts. The Research Steering Committee has attempted to create a set of CHARGE working groups that accommodate the needs and the conventions of the various cohorts. Transparency, disclosure, and professional collaborative behavior by all participating investigators have been essential to the process.

Resource limitations are another challenge. Grant applications that funded the original single-study genome-wide genotyping effort typically imagined a much simpler design. The CHS whole-genome study had as its primary aim, for instance, the analysis of data on 3 endpoints, coronary disease, stroke and heart failure. With a score of active phenotype working groups, the CHARGE collaboration broadened the scope of the short-term work well beyond initial expectations for all the participating cohorts.

One of the premier challenges has been communications among scores of investigators at a dozen sites. CHS and ARIC are themselves multi-site studies. To be successful, the CHARGE collaboration has required effective communications: (1) within each cohort; (2) between cohorts; (3) within the CHARGE working groups; and (4) among the major CHARGE committees. In addition to the traditional methods of conference calls and email, the CHARGE “wiki,” set up by Dr J. Bis (Seattle, Wash), has provided a crucial and highly functional user-driven website for calendars, minutes, guidelines, working group analysis plans, manuscript proposals, and other documents. In the end, there is no substitute for face-to-face meetings, especially at the beginning of the collaboration, and this complex meta-organization has benefited from several CHARGE-wide meetings.

The major emerging opportunity is the collaboration with other studies and consortia. Many working groups have already incorporated nonmember studies into their efforts. Several working groups have coordinated submissions of initial manuscripts with the parallel submission of manuscripts from other studies or consortia. Several working groups have embarked on plans for joint meta-analyses between CHARGE and other consortia. CHARGE has tried to acknowledge and reward the efforts of champions, who assume leadership responsibility for moving these large complex projects forward and who are often hard-working young investigators, the key to the future success of population science.

The CHARGE Consortium represents an innovative model of collaborative research conducted by research teams that know well the strengths, the limitations, and the data from 5 prospective population-based cohort studies. By leveraging the dense genotyping, deep phenotyping and the diverse expertise, prospective meta-analyses are underway to identify and replicate the major common genetic determinants of risk factors, measures of subclinical disease, and clinical events for cardiovascular disease and aging.

SOURCE:

Circulation: Cardiovascular Genetics.2009; 2: 73-80

doi: 10.1161/ CIRCGENETICS.108.82974

 

Read Full Post »


Detecting and Treating Silent Heart Disease: NewYork-Presbyterian Hospital and Weill Cornell Medical College Launch New Institute

Reporter: Aviva Lev-Ari, PhD, RN

 

UPDATED on 7/15/2018

The Dalio Institute

The Dalio Institute for Cardiovascular Imaging at NewYork-Presbyterian Hospital combines research, clinical care and education to uncover new answers about preventing heart disease. A joint NewYork-Presbyterian Hospital and Weill Cornell Medicine venture, the institute employs a multidisciplinary, multimodality approach to the detection and treatment of heart disease. Directed by Dr. James K. Min, the institute’s mission is to innovate, integrate and educate, goals that will be achieved through cutting-edge research, transformations of current clinical paradigms and dissemination of knowledge.

Rooted in the central role of imaging techniques to better diagnose cardiovascular disease, the institute not only uses state-of-the-art tools such as MRI, CT and PET scanners, but also focuses on the development of novel next-generation technologies and diagnostic tests. Applying a team-based approach that draws on the expertise of physicians and scientists in radiology, cardiology, genetics, proteomics, and computational biology, the institute’s primary research initiative is to identify the specific coronary artery lesion that is responsible for heart attacks or sudden cardiac deaths.

The Dalio Institute uses imaging technologies in conjunction with other cutting-edge diagnostic tests, including blood markers of inflammation, protein expression and metabolism. The clinical program serves patients in the outpatient and inpatient setting, as well as in the emergency department. Three specific initiatives within the clinical program emphasize early identification of heart disease in women, ethnic minorities and young patients with a family history of premature heart disease.

https://hearthealth.weillcornell.org/about-us/dalio-institute

Based on your medical history, we can use calculators to estimate your risk of having a cardiovascular event over time. Risk calculators use various factors including age, sex, and race, in addition to “traditional” cardiac risk factors such as smoking, diabetes, high cholesterol and high blood pressure. Our practice uses several common risk calculators. It is important to emphasize that risk calculators may be imperfect, especially in patients with unique risk factors. These might include a family history of early heart disease or a chronic inflammatory disorder. Therefore, it may be beneficial to consider a full cardiovascular assessment to explore your personal risk and strategies to reduce it.

Risk calculators may be of interest to you, but we caution that the results should be interpreted and reviewed by a trained clinical provider.

https://hearthealth.weillcornell.org/risk-assessments

Diagnostic Tests

 

Your cardiovascular risk assessment at HeartHealth always begins with a detailed medical history and physical exam.  The physical exam is often not able to fully diagnose problems, nor is it ever able to diagnose coronary artery disease or calcification.  We therefore offer the most up-to-date noninvasive imaging studies to visualize the heart muscle, valves, blood flow and coronary arteries.  We have state-of-the-art equipment and world-renowned experts to interpret these studies.

All of the following will be offered at HeartHealth (Click on the test name to view more information):

  • Cardiac Computed Tomography Angiography (CTA)
  • Cardiac Magnetic Resonance Imaging (MRI)
  • Cardiac PET/CT
  • Echocardiogram/Doppler Transthoracic
  • Exercise Electrocardiogram or ETT (Exercise Treadmill Test)
  • Exercise Stress Echocardiogram & Dobutamine Stress Echocardiogram
  • Myocardial Perfusion Scan (aka Nuclear Stress Test)

HeartHealth

A Program of the Dalio Institute of Cardiovascular Imaging
at the NewYork-Presbyterian Hospital
1305 York Avenue, 8th Floor
New York, NY 10021 Map ThisP: (646) 962-4278 (HART)F: (646) 962-0188

 

 

November 12, 2013
Funded by a $20 million gift from the Dalio Foundation, the institute will combine research, clinical care, and education to uncover new answers about preventing heart disease
NEW YORK – To help reduce the burden of cardiovascular disease, the nation’s leading killer, NewYork-Presbyterian Hospital and Weill Cornell Medical College have created the Dalio Institute of Cardiovascular Imaging. Raymond T. Dalio, a life trustee of NewYork-Presbyterian Hospital, has made a gift of $20 million through his Dalio Foundation in support of the institute.

The Dalio Institute of Cardiovascular Imaging will employ a multidisciplinary, multimodality approach to the detection and treatment of heart disease, with a focus on finding new answers about prevention of heart disease in at-risk individuals and ultimately save lives. Its mission is to innovate, integrate, and educate, goals that will be achieved through cutting-edge research, transformations of current clinical paradigms, and dissemination of knowledge. Dr. James K. Min, an expert in cardiovascular imaging and a physician-scientist who has led several large-scale multicenter clinical trials, has been appointed director of the Dalio Institute of Cardiovascular Imaging. Dr. Min is an attending physician at NewYork-Presbyterian Hospital and a full-time faculty member in the Department of Radiology at Weill Cornell Medical College. He joins NewYork-Presbyterian/Weill Cornell from the Cedars-Sinai Medical Center, where he was director of cardiac imaging research and co-director of cardiac imaging. Rooted in the central role of imaging techniques to better diagnose cardiovascular disease, the institute will not only use state-of-the-art tools such as MRI, CT, and PET scanners, but will also focus on the development of novel next-generation technologies and diagnostic tests. Applying a team-based approach that draws on the expertise of physicians and scientists in radiology, cardiology, genetics, proteomics, and computational biology, the institute’s primary research initiative is to identify the “vulnerable plaque,” or the specific coronary artery lesion that is responsible for a future heart attack or sudden cardiac death.“The vulnerable plaque is the holy grail in the diagnostic work-up of individuals with suspected coronary artery disease, and its elusive nature has precluded the timely treatment of millions of high-risk individuals,” says Dr. Min. “We will apply an array of innovative hardware and software imaging technologies to improve identification of the vulnerable plaque, and then seek to apply these findings in large-scale multicenter clinical trials and registries to encourage full integration of our research findings into clinical practice.”
To develop the world-class clinical program to diagnose early cardiovascular disease, the Dalio Institute of Cardiovascular Imaging will use state-of-the-art imaging technologies in conjunction with other cutting-edge diagnostic tests, including blood markers of inflammation, protein expression, and metabolism. The clinical program will serve patients in the outpatient and inpatient setting, as well as in the emergency department. Three specific initiatives within the clinical program will emphasize
  • early identification of heart disease in women,
  • ethnic minorities, and
  • young patients with a family history of premature heart disease. 

The institute’s educational mission will focus on disseminating knowledge of the latest advances in cardiovascular imaging through the education of physicians, physician trainees, and allied health professionals through formal didactic curricula and symposia.

“More than half of people who die from sudden heart attacks never knew they were at risk because their underlying heart conditions had never been diagnosed,” says Dr. Min. “Many heart attacks can be prevented if people know of the extent and severity of their asymptomatic heart disease and are properly treated. By bringing together a multidisciplinary group of experts, the Dalio Institute of Cardiovascular Imaging will not just offer the latest imaging techniques for early detection, but will also develop disruptive technologies to fight the battle against heart disease. Ultimately, these pioneering methods aim to challenge current clinical paradigms in order to reduce the morbidity and mortality associated with cardiovascular disease.” 

“Establishing the Dalio Institute of Cardiovascular Imaging is an incredibly significant milestone in our fight against heart disease,” says Dr. Steven J. Corwin, CEO of NewYork-Presbyterian Hospital and a cardiologist by training. “While modern medicine offers highly sophisticated tools for treating heart disease, we still have a long way to go in terms of identifying high-risk individuals with early-stage disease so that we can prevent catastrophic outcomes and save lives. Dr. Min’s unique background, expertise, and clinical research experience make him ideally suited to lead the institute and its groundbreaking initiatives. We are thrilled that Dr. Min has joined us, and we are extraordinarily grateful to Ray Dalio for his vision and generous support.”

“The interdisciplinary nature of the new Dalio Institute of Cardiovascular Imaging exemplifies the best in translational research – investigations that can make lifesaving impact on our patients,” says Dr. Laurie H. Glimcher, the Stephen and Suzanne Weiss Dean of Weill Cornell Medical College. “Dr. Min has a proven track record of effectively testing novel theories, and we enthusiastically support what we know will be innovative research at the institute.”

NewYork-Presbyterian/Weill Cornell Medical Center, located in New York City, is one of the leading academic medical centers in the world, comprising the teaching hospital NewYork-Presbyterian and Weill Cornell Medical College, the medical school of Cornell University. NewYork-Presbyterian/Weill Cornell provides state-of-the-art inpatient, ambulatory and preventive care in all areas of medicine, and is committed to excellence in patient care, education, research and community service. Weill Cornell physician-scientists have been responsible for many medical advances – including the development of the Pap test for cervical cancer; the synthesis of penicillin; the first successful embryo-biopsy pregnancy and birth in the U.S.; the first clinical trial for gene therapy for Parkinson’s disease; the first indication of bone marrow’s critical role in tumor growth; and, most recently, the world’s first successful use of deep brain stimulation to treat a minimally conscious brain-injured patient. NewYork-Presbyterian Hospital also comprises NewYork-Presbyterian/Columbia University Medical Center, NewYork-Presbyterian/Morgan Stanley Children’s Hospital, NewYork-Presbyterian/Westchester Division, NewYork-Presbyterian/The Allen Hospital, and NewYork-Presbyterian/Lower Manhattan Hospital. NewYork-Presbyterian is the #1 hospital in the New York metropolitan area and is consistently ranked among the best academic medical institutions in the nation, according to U.S.News & World Report. Weill Cornell Medical College is the first U.S. medical college to offer a medical degree overseas and maintains a strong global presence in Austria, Brazil, Haiti, Tanzania, Turkey and Qatar. For more information, visit http://www.nyp.org and weill.cornell.edu.
SOURCE

Read Full Post »


Affordable Care Act became law in 2010, Cardiologists’ Practice Management Decisions Unclear

Reporter: Aviva Lev-Ari, PhD, RN

Washington-Watch

ACA Delays Decisions in Cardiology

Published: Jun 28, 2013

By Chris Kaiser, Cardiology Editor, MedPage Today
Since the Affordable Care Act became law in 2010, cardiologists have been mired in a fog of uncertainty, leading to delays in making important practice management decisions.

“When I get together with colleagues at national meetings, I get the sense that nobody really understands the future,” said Cam Patterson, MD, MBA, chief of the division of cardiology at the University of North Carolina at Chapel Hill.

That uncertainty “throws a wrench into the planning process,” including recruitment and benchmark setting, he told MedPage Today.

“It’s a major sea change,” added Thomas Tu, MD, director of the cardiac catheterization lab for the Louisville Cardiology Group in Louisville, Ky., who notes that physicians are “struggling” to find ways they can be influential in the new environment.

Patterson noted the plight of young cardiologists seeking jobs in a healthcare market unsure of how or when to make its next move.

“It’s challenging to hire new recruits when budgetary and human resources decisions are essentially on hold until there is a better understanding of what the ACA will bring,” he commented.

Regarding setting benchmarks, Patterson said the days of merely imagining your quality is as good as the next practice or hospital are gone.

Cold, hard data are the new norm, but which data and how best to collect and analyze them, as well as apply the results in a robust and meaningful way, are being worked out slowly.

“As with everyone else, we are scrambling to get a grip on what our quality measures are,” Patterson said.

Education and Prevention Will Be Key

Hospitalists, as well as advanced nurse practitioners and physician assistants, can help ease the workload due to the shortage of primary care providers, a shortage that is particularly acute in California, according to C. Noel Bairey Merz, MD, director of the Barbra Streisand Women’s Heart Center at Cedars-Sinai Medical Center in Los Angeles.

“If the reform happens the way it is intended, we should have an integrated healthcare system where primary prevention — management of hypertension, dyslipidemia, diabetes, smoking cessation counseling, and therapeutic lifestyle changes — is handled at the primary care level,” she said.

The truth of the matter, however, is that it takes twice as long to train the average general physician as it does an average nurse practitioner, and four times as long as the average physician assistant.

“It’s a lot to expect of physician extenders to practice primary care medicine,” Merz toldMedPage Today.

“A better system is the medical home model, with physician team leaders and physician extenders who work on protocols. The physician extenders would be licensed and would be able to work autonomously within a protocol,” she said.

Five years ago, the cardiology department at Geisinger Health Center in Danville, Pa., employed four nurse practitioners or clinical nurse specialists. Today, there are 12 and the department is seeking three more, according to James Blankenship, MD, vice president of the Society for Cardiovascular Angiography and Interventions, as well as an interventional cardiologist at Geisinger.

Blankenship also said that acknowledging the need for more primary care providers is to miss half of the equation. “We will need more specialists, as well.”

Given the newly insured patients coming into the system, as well as the aging Medicare population, cardiologists will be stretched pretty thin. But the field of cardiology has been instrumental in advocating teamwork among the different specialties for years, he said. “That’s a train that’s already on the tracks.”

Merz noted an expectation to see more cardiovascular care teams in response to the ACA. Such teams typically consist of a physician leader, nurse practitioners, pharmacists, behavioral experts, rehab professionals, and others.

These teams are vital for the care of high-risk patients such as survivors of angioplasty, bypass surgery, and heart failure, she said, especially since there aren’t enough cardiologists to do it all.

Echoing Blankenship, Merz said that cardiologists will probably be busier than ever as heart disease remains the leading killer among men and women as the population ages. She noted a decline in the most severe type of heart attack — ST-segment elevation MI, or STEMI — in the Medicare population, a decline that is likely multifactorial, but two reasons stand out as attributable to the decline — the use of low-dose aspirin and statin therapy for primary and secondary prevention, she said.

“At whatever level these medications are prescribed and managed — primary care physician, nurse practitioner, cardiologist — one thing is clear: they work and they should continue to be utilized at the front line of heart disease management,” Merz said.

Patients with chronic diseases already consume a great deal of healthcare resources. The other side of that coin is prevention, noted Kathy Berra, MSN, ANP, president of the Preventive Cardiovascular Nurses Association and a nurse at Stanford Prevention Research Center in Stanford, Calif.

“Prevention is a family affair. It’s been shown that when women take care of themselves, the health of the family improves.”

Emerging as one of the more important gatekeepers for women’s health — including cardiovascular health — are ob/gyns, Berra said.

Gynecologists have increased their efforts to quiz women about heart disease risk factors such as hypertension, high cholesterol, and diabetes. If red flags are apparent, patients can be referred to primary care providers, internal medicine physicians, or cardiologists.

“Ob/gyns are on the front line of women’s health. Perhaps under the ACA model, these specialists will have a closer relationship with cardiologists,” Berra told MedPage Today.

Regarding nurses and other care providers in hospitals, they need to be able to educate patients about how to take care of themselves post-discharge, how to understand the importance of their medications, and how to best re-connect with their nonhospital environment.

Readmission is at epidemic proportions and it can be reined in by patient education at the hospital level. Even pharmacists are getting more involved in patient education.

Scott & White Hospital in Temple, Texas, has a program that encourages adherence by waiving drug copays following an education session, according to James Rohack, MD, director of the Center for Healthcare Policy at Scott & White.

Patients on Seniorcare who are on five medications or more are asked if they want to participate in the program. If they agree, they meet with a pharmacist once a month for 15 to 30 minutes. The pharmacist goes over everything about the patient’s medication, listens to any concerns, and sends him or her home with new medications, waiving the copay.

“Having no copay is a great benefit for patients on fixed incomes, but it goes beyond that. A little bit of education goes a long way and if patients can be reminded once a month about the importance of taking their medications, we will have fewer hospitalizations,” Rohack said.

Accountable Care Organizations

The development of ACOs is probably one of the biggest challenges under the ACA, said Geisinger’s Blankenship.

The promise of ACOs is to have better integrated care, less fragmented care among various providers. Part of this integrated care involves incentives to minimize procedures that are either unnecessary or could be replaced with a less costly treatment.

“Having been under a fee-for-service model for a long time, some in cardiology might find the new paradigm challenging,” Blankenship suggested.

ACOs are supposed to help take the sting out of moving away from the fee-for-service model by providing the opportunity for better coordinated care — which should translate into a higher quality of care.

However, ACOs can be difficult to set up, especially from scratch, as they have a large startup cost, he said.

One of the most important aspects of an ACO is to have a solid network of primary care doctors. Patterson, at UNC Chapel Hill, said the uncertainty of whether his state will expand Medicaid has led to the “very aggressive acquisition of primary care practices.”

“The goal is to have enough physicians and patients so that we will have a low-cost ACO when we are ready to implement that model. We are going to need about 1 million patients to have an efficient ACO,” he said.

But there are also fears that the ACA will deluge cardiologists with paperwork.

“In the clinic, I spend as much time with paperwork as I do with patients — particularly with Medicare and Medicaid patients,” noted John Day, MD, director of Heart Rhythm Services at Intermountain Medical Center in Salt Lake City, Utah. “Many of us are worried we haven’t even seen the beginning of the deluge.”

The intrusion of paperwork and other government regulations tends to erode the time physicians get to spend with patients — “one of the primary reasons I wanted to be a doctor,” Day said.

In addition, Day said that he and many of his colleagues are disappointed that the ACA did not address malpractice concerns. “Perhaps it’s not so much what’s in the bill as what is not in the bill,” he said.

“Malpractice concerns are real; they scare me every day; it affects how you practice medicine. I don’t see how you can rein in costs without addressing the malpractice quagmire,” Day told MedPage Today.

Shifting Sands

“For those of us working in the trenches, we have a vague concept of the changes coming down the road,” said James A. de Lemos, MD, director of the coronary care unit at Parkland Memorial Hospital in Dallas.

“We seem to be too busy to think about the changes, which leads to one of my biggest worries — that I won’t have prepared my troops well enough,” he said.

From a clinical perspective, it’s business as usual, with de Lemos and colleagues focused on growth and the development of referrals and procedure services.

“We are concerned, however, that the entire paradigm is going to shift and what we’re building today might not be financially sound in the ACO model,” de Lemos told MedPage Today.

De Lemos, who is active in cardiovascular biomarker research, suggested that biomarkers will become more important in the ACA era of healthcare.

“It will no longer be prudent to send everyone with a complaint to a cardiologist,” he commented. “Biomarker screening may play a role as a triage method to separate out those who merit a trip to the cardiologist from those who can be treated by primary care doctors.”

Rohack made these suggestions for getting ready for the changes associated with the ACA:

  • Make sure you are actively aware of your quality measures, your individual quality measures.
  • When caring for uninsured adults, make sure you are aware of the potential benefits with health insurance exchanges, because they may qualify.
  • Make sure you are aware of impending deadlines regarding the implementation of certain aspects associated with electronic medical records because penalties can be assessed for missing deadlines.

 

Who Takes the Lead?

There are a lot of moving pieces that will contribute to finding success in the new era of healthcare and leaders must emerge to help forge pathways that others can follow. Hospitalists will be among those leaders, says Jeffrey H. Barsuk, MD, MS, a hospitalist and director of Simulation and Patient Safety for Graduate Medical Education at Northwestern University Feinberg School of Medicine in Chicago.

“At our hospital, we are probably the largest group of physicians involved in healthcare safety, quality, and reform,” he said.

The ACA, he told MedPage Today, is starting to have more of an impact on how he and his colleagues position themselves for the future.

In particular, the new bundled payment and fee-per-encounter models are ideal scenarios where hospitalists can make a difference by bridging gaps in the continuity of care and helping to shorten the length of stay without compromising quality.

Hospitalists can, for example, provide smoking cessation counseling for heart patients, discuss the importance of medication adherence, and check to ensure there are no contraindications to the medications or no potential for drug-drug adverse interactions.

Ultimately, though, clinicians at all levels, primary care practitioners and specialists, will need to work closely together because, as interventionalist Tu noted, government intervention that is not well thought out can backfire. The ACA might save money in the short run, Tu said, but in the long term, there is a great potential “to damage the care of patients and harm the profession of medicine. Already many good people don’t want to be in the field anymore.”

http://www.medpagetoday.com/Washington-Watch/Reform/40164?xid=nl_mpt_DHE_2013-06-29&utm_content=&utm_medium=email&utm_campaign=DailyHeadlines&utm_source=WC&eun=g406134d0r&userid=406134&email=serbangg@gmail.com&mu_id=5783576 

Read Full Post »


Emerging Clinical Applications for Cardiac CT: Plaque Characterization, SPECT Functionality, Angiogram’s and Non-Invasive FFR

Author, and Content Consultant to e-SERIES A: Cardiovascular Diseases: Justin Pearlman, MD, PhD, FACC

and

Article Curator: Aviva Lev-Ari, PhD, RN

 

UPDATED on 7/25, 2018

VIDEOS | CT ANGIOGRAPHY (CTA) | JULY 19, 2018

VIDEO: Using FFR-CT in Everyday Practice

Kavitha Chinnaiyan, M.D., FACC, FSCCT, associate professor, Oakland University, William Beaumont School of Medicine, Royal Oak, Mich. She presented at the Society of Cardiovascular Computed Tomography (SCCT) 2018 meeting.

VIEW VIDEO 

https://www.dicardiology.com/videos/video-using-ffr-ct-everyday-practice?eid=333021707&bid=2184627

Related FFR-CT Content:

Clinical Applications of FFR-CT

VIDEO: Implementation and the Science Behind FFR-CT — interview with James Min, M.D.

VIDEO: Early U.S. Experience With FFR-CT in Evaluating ED Chest Pain Presentation — interview with Simon Dixon, M.D.

VIDEO: Status of FFR-CT Adoption in the United States — interview with Campbell Rogers, M.D.

Clinical studies of coronary anatomy by computed tomography use equipment with various numbers of concurrent slices through the heart: 1, 4, 16, 32, 64, 128, and recently 256 or more. Like interventional catheterization, iodine is injected to make the inside of the coronary arteries opaque to xray transmission, to create contrast (otherwise the xray of the coronary tree would be like a photograph of a white polar bear in a snow storm; the contrast acts like spray paint). Computed tomographic angiography (CTA) uses a similar or higher dye load than catheterization, and provides generally lower imaging quality than catheterization but with 3-dimensional reconstruction instead of flat projection (hundreds of linear views at different angles versus one or two image planes at a time). The results from CTA are generally deemed qualitative: whther or not there are potentially flow-limiting lesions in the major branch arteries that supply the heart (with exception: the posterior descending artery to the inferior wall of the heart is not reliably seen). Catheter-based projection coronary angiography sees smaller branches with finer ability to measure the degree of lumen narrowing. However, other imaging methods show greater promise in identifying plaque character. The following examines initial enthusiasm for improvements in CTA which offer better results compared to current clinical CTA and hope to offer advantages over catheter-based methods beyond the avoidance of catheters.

I. Cardiac CT Challenging Functionality of SPECT and Angiogram

Noninvasive computed tomography (CT) perfusion imaging added to CT angiography accurately identifies flow-limiting coronary lesions that need to be treated, results of the CORE320 trial show.

Dr João AC Lima (Johns Hopkins University, Baltimore, MD) presented results of the 381-patient, 16-center trial, which showed that stress CT myocardial perfusion analysis (CTP) significantly improves the diagnostic power of rest CT angiography (CTA) alone. The study also showed that the CTA+CTP strategy has about the same power to identify patients who need revascularization within 30 days as the current standard strategy of invasive angiography plus a single photon-emission computed tomography (SPECT) myocardial perfusion imaging (MPI) test.

Lima explained that the potential advantage of the CT-based approach is that it can obtain information on myocardial perfusion and coronary flow in two scans about 10 minutes apart and is noninvasive.

All patients in the study had been referred for an invasive angiogram to investigate suspected or known coronary artery disease (CAD), but all patients underwent a rest CTA, stress CTP, and SPECT-MPI test in addition to the invasive angiogram. Invasive angiography alone identified apparently obstructive coronary disease in 59% of patients, but adding the SPECT-MPI information reduced that number to 38%.

The accuracy of the CTA+CTP approach was measured as the area under the receiver-operating-characteristic curve. When 50% greater stenosis on invasive angiography was set as the reference standard for a flow-limiting stenosis, the accuracy of the CTA+CTP approach for detecting flow-limiting CAD was 0.87 on a per-patient basis. When the standard was >70% stenosis, the accuracy of the CTA+CTP approach was 0.89.

 

 VIEW VIDEO on CORE320 with Dr João Lima
Flow Limiting Lesion (low perfusion) vs. Anatomic Stenosis Severity
SOURCES

II. FFR-CT

Results of the Diagnosis of Ischemia-Causing Stenoses Obtained via Noninvasive Fractional Flow Reserve (DISCOVER FLOW) study show that the coronary stenoses that cause ischemia can be identified noninvasively with computer analysis of coronary computed tomography angiograms (CCTAs) [1].

“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) 

Imaging technology Accuracy(%) Sensitivity(%) Specificity(%) Positive predictive value (%) Negative predictive value (%)
FFRCTa  84.3 87.9 82.2 73.9 92.2
CCTAb 58.5 91.4 39.6 46.5 88.9

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

SOURCES

III. Ten Emerging Uses for Cardiac CT from SCCT 2013

July 11-14, 2013
Palais des congrès
Montréal, Québec, Canada

JULY 16, 2013  – heartwire

Dr Matthew Budoff (Los Angeles Biomedical Research Institute, CA), a longtime researcher in the use of cardiac CT, described what he believes to be the most important uses for CT today [1].

First, CT angiography is emerging as “a single tool that gives us [information about] function and anatomy,” he told the audience.

Second, it is now known that patients are more likely to have a cardiovascular event if they have low-attenuation plaque (soft plaque), positive remodeling, and spotty calcification, he explained. If a clinician were limited to looking only at plaque or stenosis, he would advise him or her to “just read the CTA for plaque and plaque characteristics and [don’t] read it for stenosis severity, and you’ll probably serve your patients better in predicting risk” of a cardiovascular event. “I think in future we’re going to be using plaque characterization in every case,” he added. “I certainly don’t advocate stenting these patients [who have vulnerable plaque] yet, but . . . I do treat these patients more aggressively.”

Third, coronary CT angiography is a noninvasive way to identify complex aortic-valve geometry and guide TAVR.

“With perfusion imaging, TAVR, and plaque assessment leading the way, the increased utilization of CTA is certain,” Budoff concluded. “However, more validation work is needed to ensure that industry and payers accept these applications.”

Speaking to heartwire, Budoff singled out TAVR as “an easy launching point for doctors to get familiar with” CT angiography. He also believes that using CT for “heart-failure assessment or even plaque assessment . . . will really add value to their practice.” CT also allows clinicians to “start getting a handle on what’s causing stenosis [in a patient], what it looks like, and . . . how severe the stenosis is.”

In a separate presentation [2], Dr James K Min (Cedars-Sinai, Los Angeles, CA) identified the same three clinical applications as Budoff in his “top 10 things to watch” in coronary CT in the coming year. He identified his “up-and-coming areas to watch” in the following order:

  • Dual-energy CT scanners. This hardware, when combined with new software, is producing enhanced image quality that allows, for example, a “plaque biopsy,” which provides detailed information about plaque characteristics.
  • Myocardial CT perfusion. “We’ve looked at this for seven years, and I think it’s starting to become ready for prime time,” said Min. In the next year, he expects investigators to figure out exactly how to use CT to look at coronary flow reserve.
  • Computational fluid dynamics. Exciting work is being done, for example, using a virtual stent to see how a real stent would potentially resolve a patient’s ischemia.
  • PlaqueCoronary CT can do more than identify how many vessels are blocked, he said, echoing Budoff’s words. It is enabling investigators to study the pathogenesis of atherosclerosis. “We’re going to be able to identify plaque characteristics beyond stenosis for the prediction of acute MI,” Min said.
  • Structural heart disease. CT is already being used to help guide TAVR to reduce postsurgery complications.
  • Radiation-dose reduction. Min weighed in and said, “I think it’s becoming a nonissue.” He noted that during the past year, investigators reported how coronary CT angiography can be used with radiation doses as low as 0.01 mSv, (should be 1mSv) whereas a screening mammogram exposes a woman to 0.05 mSv of radiation. (1/5 of mammography)
  • Contrast-agent reduction.”I think we will see improvements—we will get to the 10-cc scan,” Min predicted.
  • Appropriate-use criteria. Physicians are continuing to identify which patients benefit from cardiac CT, as the technology is advancing.
  • Two trialsAmong the many ongoing trials in the field, Min identified two to watch. The PROMISEstudy is comparing functional vs anatomic testing to identify heart disease. The Coronary Computed Tomographic Angiography for Selective Cardiac Catheterization (CONSERVE) trial is looking at using CT as a “gatekeeper” to the cath lab, to identify which patients should be sent for invasive coronary angiography and which ones have only have mild stenosis and could be sent home and treated with medical therapy .
  • Worldwide growth in CT. Collaboration with investigators around the world is growing, and the SCCT meetings next year in Hawaii and China will offer more opportunities for this.
Budoff has received research/grant support from HeartFlow, study funding from Wakunaga of America and GE Healthcare and has been a consultant and speaker for GE Healthcare. Min has received research/grant support fromGE Healthcare, Phillips Healthcare, and Vital Images and study funding from Astellas. He has been a consultant for GE Healthcare and Arineta and on the speaker’s bureau for GE Healthcare. He holds equity interest in TC3 and MDXX.

Sources

  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

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 

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.

The study was funded by Astellas. Cury is a consultant for Astellas and has received research grants from Astellas and GE Healthcare. Hoe has received grant and research support and travel funding from Toshiba Medical Systems and is on its speaker’s bureau. 

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. 

REFERENCES
1. M Henzlova, EJ Levine, S Moonthungal, et al. A protocol for the provisional use of perfusion imaging with exercise stress testing. Abstract no 70123.
2. Bourque JM, Charlton GT, Holland BH, et al. Prognosis in patients achieving >10 METS on exercise stress testing: was SPECT imaging useful? J Nucl Cardiol 2011, 2 230-7.
European Society of Cardiology
SOURCE

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.
REFERENCES

Sources

  1. Shah BN, Balaji G, Alhajiri A, et al. The incremental diagnostic and prognostic value of contemporary stress echo in a chest pain unit: mortality and morbidity outcomes from a real-world setting. Circ Cardiovasc Imaging 2012; DOI:10.1161/CIRCIMAGING.112.980797. Available at: http://circimaging.ahajournals.org.
  2. Jeetley P, Burden L, Stoykova B, Senior R. Clinical and economic impact of stress echocardiography compared with exercise electrocardiography in patients with suspected acute coronary syndrome but negative troponin: a prospective randomized controlled study. Eur Heart J. 2007; 28:204-211.

http://www.theheart.org/article/1490677.do

VII. PET Perfusion Imaging Improves Risk Estimates

12/5/2012 Reed Miller

Boston, MA – New data from a large multicenter registry suggest that positron-emission-tomography (PET) myocardial perfusion imaging (MPI) can greatly improve the accuracy of risk estimation in coronary disease patients compared with a model based on traditional risk factors [1].

Only small single-center studies have demonstrated the prognostic value of PET MPI in predicting which patients are at greatest risk for coronary disease events. So Dr Sharmila Dorbala (Brigham and Women’s Hospital, Boston) and colleagues analyzed outcomes from 7061 patients from four centers who underwent a clinically indicated rest/stress rubidium-82 PET MPI test.

Results of the study are published online December 5, 2012 in the Journal of the American College of Cardiology. “The results of the current study are critical to advance the field and guide more effective use of PET MPI in clinical practice,” Dorbala et al state.

Median follow-up was 2.2 years. During follow-up, there were 169 cardiac arrests and 570 all-cause deaths. Net reclassification improvement and integrated discrimination analyses showed that the risk-adjusted hazard of cardiac death increases as the percentage of abnormal myocardium increases. A mildly abnormal stress test is associated with a 2.3 times greater risk of cardiac death than a normal test. The hazard ratio for a severely abnormal test is 4.9.

The addition of PET MPI measurements of myocardial ischemia and myocardial scarring to traditional clinical information improves the performance of a risk prediction model based on traditional risk factors (C statistic 0.805-0.839) as well as risk reclassification for cardiac death, with small improvements in risk assessments for all-cause death. The assessment of the magnitude of ischemia and scar added to the reclassification of risk for cardiac death in one in every nine patients who underwent clinical PET MPI in the study.

Unlike computed-tomography (CT) coronary angiography, perfusion imaging provides information about myocardial blood flow and accounts for underlying coronary disease, collateral flow, and myocardial adaptation to wall stress and can be used in patients with renal insufficiency, the authors point out. Compared with single-photon-emission computed tomography (SPECT) perfusion imaging, PET MPI offers better image quality, test specificity for the diagnosis of obstructive coronary disease, and identification of scar and ischemia, according to Dorbala et al, and PET MPI uses a lower effective radiation dose. However, while the prognostic value of SPECT MPI has been described in tens of thousands of patients, the prognostic value of PET MPI has been studied in only a few thousand patients.

Does more risk information help?

The value of the prognostic information offered by PET MPI is not yet clear, according to an accompanying editorial by Drs Paul Schoenhagen and Rory Hachamovitch (Cleveland Clinic, OH) [2]. “Rather than assessing whether a test yields improvement in risk assessment, the focus [should be] shifted to whether a test can identify which patients will gain a benefit from a specific therapeutic approach,” they write. “The role of testing [should be] defined in the context of a specific intervention and whether the effectiveness of the intervention is improved by the use of an imaging study to identify optimal candidates for treatment.

“However, this process is neither simple nor inexpensive and will require prospective randomized clinical trials, validating the results and hypotheses generated by observational data,” the editorialists conclude.

Commenting on the study, Dr Kavitha Chinnaiyan (William Beaumont Hospital, Royal Oak, MI) toldheartwire, “While the details of downstream management of these patients are unclear in this paper, the association of ischemia with mortality is clear, as is the reclassification of risk. The next step in terms of management of ischemic patients is really the question here.” She also pointed out that the ongoingISCHEMIA trial, comparing angiography and revascularization plus optimal medical therapy with optimal medical therapy only, may provide more insights on the best option for patients who show more than mild ischemia on stress studies.

Dorbala has received research grants from Astellas Pharma and Bracco Diagnostics; has served on advisory boards for Astellas Pharma; and has received honoraria from MedXcelDisclosures for the coauthors are listed in the paper.Schoenhagen and Hachamovitch report that they have no relationships relevant to the contents of this paper to discloseChinnaiyan has no relevant disclosures.

REFERENCES

  1. Dorbala S, Di Carli M, Beanlands RS, et al. Prognostic value of stress myocardial perfusion positron emission tomography. J Am Coll Cardiol 2013; DOI:10.1016/j.jacc.2012.09.044. Available at:http://content.onlinejacc.org.
  2. Schoenhagen P and Hachamovitch R. Evaluating the clinical impact of cardiovascular imaging: Is a risk-based stratification paradigm relevant. J Am Coll Cardiol 2013; DOI:10.1016/j.jacc.2012.09.044. Available at:http://content.onlinejacc.org.

SOURCE

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

https://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

https://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

https://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

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

Read Full Post »

Older Posts »