Morten Krogh Christiansen, MD, Department of Cardiology, Aarhus University Hospital, Aarhus, Denmark speaks about Polygenic Risk Score–Enhanced Risk Stratification of Coronary Artery Disease in Patients With Stable Chest Pain.
Link to AHA Article:
https://www.ahajournals.org/doi/abs/10.1161/CIRCGEN.120.003298
Summary -
Backstory:
Although polygenic risk scores (PRSs) have been linked to coronary artery disease (CAD), the therapeutic utility of utilizing PRSs for risk stratification at the single-patient level has yet to be determined. We wanted to see if adding a PRS to clinical risk factors (CRFs) improved risk classification in individuals who were referred for coronary computed tomography angiography because they were suspected of having obstructive CAD.
Methodologies:
We recruited 1617 patients with stable chest symptoms and no history of CAD who were referred for coronary computed tomography angiography in this prespecified diagnostic substudy of the Dan-NICAD trial (Danish study of Non-Invasive testing in Coronary Artery Disease). Age, sex, symptoms, past or active smoking, antihypertensive medication, lipid-lowering treatment, and diabetes were all utilized as CRFs for risk classification. Patients' genotypes were also determined, as well as their PRSs. A coronary computed CT angiography was performed on all of the patients. Invasive coronary angiography with fractional flow reserve was also performed on patients suspected of having a 50% stenosis. Visual invasive coronary angiography stenosis >90%, fractional flow reserve 0.80, or quantitative coronary analysis stenosis >50% if fractional flow reserve measurements were not possible were used to establish a combined endpoint of obstructive CAD.
Outcomes:
Independent of CRFs, the PRS was linked to obstructive CAD (adjusted odds ratio, 1.8 [95 percent CI, 1.5–2.2] per SD). The PRS showed a 0.63 (0.59–0.68) area under the curve, which was similar to that of age and sex. When the PRS and CRFs were combined, the CRF+PRS model had an AUC of 0.75 (0.71–0.79), which was 0.04 higher than the CRF model (P=0.0029). The use of pretest probability (pretest probability) cutoffs of 5% and 15% resulted in a net reclassification improvement of 15.8% (P=3.1104), with a down-classification of risk in 24 percent of patients (211 of 862) who had a pretest probability of 5% to 15% based on CRFs alone.
Findings:
Beyond CRFs, adding a PRS enhanced risk classification of obstructive CAD, indicating that PRSs might be used to guide diagnostic testing in the modern clinical context.
Coronary Artery Disease
Description
Coronary Artery Disease
In 1997, Dr. Bittl joined Dr. Feldman's staff at the MRMC Cath Lab (now AdventHealth Ocala). He graduated from Johns Hopkins University in Baltimore, Maryland, with a medical degree. He did his residency and cardiology fellowship at UCLA Hospital in Los Angeles, CA, and Brigham and Women's Hospital in Boston, MA. Dr. Bittl also worked as an associate professor of medicine at Harvard Medical School. In this video Dr. Bittl speaks on Putting the 2021 ACC/AHA/SCAI Guideline for Coronary Artery Revascularization Into Practice: A Case Series.
https://www.jacc.org/doi/10.1016/j.jaccas.2021.09.025
In selected subsets of patients with stable ischemic heart disease and complex coronary disease with or without left ventricular dysfunction, the 2021 ACC/AHA/SCAI guideline for coronary artery revascularization can be used to decide between revascularization and optimal medical therapy to reduce mortality or cardiovascular events. (Advanced level of difficulty.)
Introduction
The ISCHEMIA (International Study of Comparative Health Effectiveness with Medical and Invasive Approaches) (1) trial debunked the conventional wisdom that routine revascularization with either coronary artery bypass graft (CABG) surgery or percutaneous coronary intervention (PCI) improves survival in patients with multivessel (MV) coronary artery disease (CAD) and stable ischemic heart disease (SIHD), a belief that was based on the findings of several early studies and was supported by (2). The ACC/AHA/SCAI guideline drafting committee for coronary artery revascularization in 2021 (3) has analyzed the results of the new trial (1) against the background of existing evidence to identify patient subsets likely to benefit from revascularization in terms of survival. The following case series demonstrates how doctors can utilize the 2021 guideline (3) to assess which patients with SIHD may benefit from revascularization over medical therapy (MT) alone in terms of survival or cardiovascular events.
In 1997, Dr. Bittl joined Dr. Feldman's staff at the MRMC Cath Lab (now AdventHealth Ocala). He graduated from Johns Hopkins University in Baltimore, Maryland, with a medical degree. He did his residency and cardiology fellowship at UCLA Hospital in Los Angeles, CA, and Brigham and Women's Hospital in Boston, MA. Dr. Bittl also worked as an associate professor of medicine at Harvard Medical School. In this video Dr. Bittl speaks on Putting the 2021 ACC/AHA/SCAI Guideline for Coronary Artery Revascularization Into Practice: A Case Series.
https://www.jacc.org/doi/10.1016/j.jaccas.2021.09.025
In selected subsets of patients with stable ischemic heart disease and complex coronary disease with or without left ventricular dysfunction, the 2021 ACC/AHA/SCAI guideline for coronary artery revascularization can be used to decide between revascularization and optimal medical therapy to reduce mortality or cardiovascular events. (Advanced level of difficulty.)
Introduction
The ISCHEMIA (International Study of Comparative Health Effectiveness with Medical and Invasive Approaches) (1) trial debunked the conventional wisdom that routine revascularization with either coronary artery bypass graft (CABG) surgery or percutaneous coronary intervention (PCI) improves survival in patients with multivessel (MV) coronary artery disease (CAD) and stable ischemic heart disease (SIHD), a belief that was based on the findings of several early studies and was supported by (2). The ACC/AHA/SCAI guideline drafting committee for coronary artery revascularization in 2021 (3) has analyzed the results of the new trial (1) against the background of existing evidence to identify patient subsets likely to benefit from revascularization in terms of survival. The following case series demonstrates how doctors can utilize the 2021 guideline (3) to assess which patients with SIHD may benefit from revascularization over medical therapy (MT) alone in terms of survival or cardiovascular events.
Dr. Christine Albert, MD works in the Department of Cardiology at the Smidt Heart Institute at Cedars-Sinai Medical Center in Los Angeles, California. In This video Dr. Albert discusses Diabetes and the Risk of Sudden Death in Coronary Artery Disease Patients Without Severe Systolic Dysfunction.
Link to Abstract-
https://www.jacc.org/doi/10.1016/j.jacep.2021.05.014
Abstract
In patients with coronary artery disease (CAD) who do not qualify for implantable cardioverter-defibrillators, this study sought to determine the absolute and relative associations of diabetes mellitus (DM) and hemoglobin A1c (HbA1c) with sudden and/or arrhythmic death (SAD) versus other modes of death.
Background
Patients with CAD and diabetes are at an increased risk of SAD; however, given competing causes of death, it is unclear whether these patients would benefit from implantable cardioverter-defibrillators and/or whether HbA1c could help with SAD risk stratification.
Methods
Competing risk analyses were used to compare the absolute and relative risks of SAD versus non-SAD by DM status and HbA1c level in the PRE-DETERMINE study of 5,764 patients with CAD with left ventricular ejection fraction (LVEF) of >30% to 35 percent and to identify risk factors for SAD among 1,782 patients with DM.
Results
DM and HbA1c were significantly associated with SAD and non-SAD over a median follow-up of 6.8 years (P 0.05 for all comparisons); however, the cumulative incidence of non-SAD (19.2 percent; 95 percent CI: 17.3 percent -21.2 percent) in DM patients was nearly 4 times higher than SAD (4.8 percent; 95 percent CI: 3.8 percent -5.9 percent). Absolute risk followed a similar pattern across HbA1c groups. HbA1c was not connected with SAD in studies limited to diabetic patients, although decreased LVEF, atrial fibrillation, and ECG measures were all linked to a higher risk of SAD.
Conclusions
Patients with CAD and LVEF of >30% to 35% who had DM and/or increased HbA1c have a considerably higher absolute risk of dying from non-SAD than from SAD. Clinical risk factors, not HbA1c, were linked to the incidence of SAD in diabetic individuals. (NCT01114269; PRE-DETERMINE: Biologic Markers and MRI SCD Cohort Study)
Dr. Christine Albert, MD works in the Department of Cardiology at the Smidt Heart Institute at Cedars-Sinai Medical Center in Los Angeles, California. In This video Dr. Albert discusses Diabetes and the Risk of Sudden Death in Coronary Artery Disease Patients Without Severe Systolic Dysfunction.
Link to Abstract-
https://www.jacc.org/doi/10.1016/j.jacep.2021.05.014
Abstract
In patients with coronary artery disease (CAD) who do not qualify for implantable cardioverter-defibrillators, this study sought to determine the absolute and relative associations of diabetes mellitus (DM) and hemoglobin A1c (HbA1c) with sudden and/or arrhythmic death (SAD) versus other modes of death.
Background
Patients with CAD and diabetes are at an increased risk of SAD; however, given competing causes of death, it is unclear whether these patients would benefit from implantable cardioverter-defibrillators and/or whether HbA1c could help with SAD risk stratification.
Methods
Competing risk analyses were used to compare the absolute and relative risks of SAD versus non-SAD by DM status and HbA1c level in the PRE-DETERMINE study of 5,764 patients with CAD with left ventricular ejection fraction (LVEF) of >30% to 35 percent and to identify risk factors for SAD among 1,782 patients with DM.
Results
DM and HbA1c were significantly associated with SAD and non-SAD over a median follow-up of 6.8 years (P 0.05 for all comparisons); however, the cumulative incidence of non-SAD (19.2 percent; 95 percent CI: 17.3 percent -21.2 percent) in DM patients was nearly 4 times higher than SAD (4.8 percent; 95 percent CI: 3.8 percent -5.9 percent). Absolute risk followed a similar pattern across HbA1c groups. HbA1c was not connected with SAD in studies limited to diabetic patients, although decreased LVEF, atrial fibrillation, and ECG measures were all linked to a higher risk of SAD.
Conclusions
Patients with CAD and LVEF of >30% to 35% who had DM and/or increased HbA1c have a considerably higher absolute risk of dying from non-SAD than from SAD. Clinical risk factors, not HbA1c, were linked to the incidence of SAD in diabetic individuals. (NCT01114269; PRE-DETERMINE: Biologic Markers and MRI SCD Cohort Study)
Dr. Mouaz H. Al-Mallah is a cardiologist working at Houston Methodist Hospital in Houston, Texas. He graduated from the American University of Beirut Faculty of Medicine with a medical degree. In this video Dr. Al-Mallah discusses
Link to Abstract-
https://www.jacc.org/doi/10.1016/j.jcmg.2021.01.024
Abstract-
Objectives
The aim of this analysis is to examine the incremental prognostic value of coronary artery calcium (CAC) score and myocardial flow reserve (MFR) in patients with suspected coronary artery disease (CAD) undergoing positron emission tomography (PET) myocardial perfusion imaging (MPI).
Background
Advances in cardiac PET and computed tomography imaging enabled the simultaneous acquisition of anatomic and physiological data for patients suspected of CAD.
Methods
Consecutive patients who underwent PET MPI and CAC score calculation at King Abdulaziz Cardiac Center, Riyadh, Saudi Arabia, between May 2011 and May 2018 were included in the study. MPI and CAC images were obtained in the same setting. The primary endpoint of the study was a composite of cardiac death and nonfatal myocardial infarction. Cox proportional hazard regression was used to assess the incremental prognostic value of CAC and MFR by sequentially adding the variables to a model that included clinical and PET variables.
Results
A total of 4,008 patients (mean age 59.7 ± 11.6 years, 55% women) were included in the analysis. Risk factors were prevalent (77.6% hypertension, 58.1% diabetes). In total, 35.9% of the cohort had CAC of 0, 16.5% had CAC ≥400, and 43.9% had MFR <2. Over a median follow up of 1.9 years, 130 (3.2%) patients had cardiac death/nonfatal myocardial infarction. CAC and MFR score added incremental prognostic value over clinical and perfusion variables (base model: c-index 0.8137; Akaike information criterion [AIC]: 1,865.877; p = 0.0011; CAC model: c-index = 0.8330; AIC: 1,850.810; p = 0.045 vs. base model; MFR model: c-index = 0.8279; AIC: 1,859.235; p = 0.024). Combining CAC and MFR did not enhance risk prediction (c-index = 0.8435; AIC: 1,846.334; p = 0.074 vs. MFR model; p = 0.21 vs. CAC model.)
Conclusions
In this large cohort of patients referred for PET MPI, both CAC and MFR independently added incremental prognostic value over clinical and MPI variables. Although combining both may have synergetic prognostic effect, this relation was not shown in multivariable model of this analysis.
Dr. Mouaz H. Al-Mallah is a cardiologist working at Houston Methodist Hospital in Houston, Texas. He graduated from the American University of Beirut Faculty of Medicine with a medical degree. In this video Dr. Al-Mallah discusses
Link to Abstract-
https://www.jacc.org/doi/10.1016/j.jcmg.2021.01.024
Abstract-
Objectives
The aim of this analysis is to examine the incremental prognostic value of coronary artery calcium (CAC) score and myocardial flow reserve (MFR) in patients with suspected coronary artery disease (CAD) undergoing positron emission tomography (PET) myocardial perfusion imaging (MPI).
Background
Advances in cardiac PET and computed tomography imaging enabled the simultaneous acquisition of anatomic and physiological data for patients suspected of CAD.
Methods
Consecutive patients who underwent PET MPI and CAC score calculation at King Abdulaziz Cardiac Center, Riyadh, Saudi Arabia, between May 2011 and May 2018 were included in the study. MPI and CAC images were obtained in the same setting. The primary endpoint of the study was a composite of cardiac death and nonfatal myocardial infarction. Cox proportional hazard regression was used to assess the incremental prognostic value of CAC and MFR by sequentially adding the variables to a model that included clinical and PET variables.
Results
A total of 4,008 patients (mean age 59.7 ± 11.6 years, 55% women) were included in the analysis. Risk factors were prevalent (77.6% hypertension, 58.1% diabetes). In total, 35.9% of the cohort had CAC of 0, 16.5% had CAC ≥400, and 43.9% had MFR <2. Over a median follow up of 1.9 years, 130 (3.2%) patients had cardiac death/nonfatal myocardial infarction. CAC and MFR score added incremental prognostic value over clinical and perfusion variables (base model: c-index 0.8137; Akaike information criterion [AIC]: 1,865.877; p = 0.0011; CAC model: c-index = 0.8330; AIC: 1,850.810; p = 0.045 vs. base model; MFR model: c-index = 0.8279; AIC: 1,859.235; p = 0.024). Combining CAC and MFR did not enhance risk prediction (c-index = 0.8435; AIC: 1,846.334; p = 0.074 vs. MFR model; p = 0.21 vs. CAC model.)
Conclusions
In this large cohort of patients referred for PET MPI, both CAC and MFR independently added incremental prognostic value over clinical and MPI variables. Although combining both may have synergetic prognostic effect, this relation was not shown in multivariable model of this analysis.
Professor Paul Myles, MD is the current Director of Anaesthesia and Perioperative Medicine at the Alfred and the Chair of the Academic Board of Anaesthesia and Perioperative Medicine. Professor Myles is also a Fellow of the Australian Academy of Health and Medical Sciences and an Australian NHMRC Practitioner Fellow. In this video Dr. Myles speaks about The ENIGMA II Trial: Nitrous Oxide Anesthesia and Cardiac Morbidity After Major Surgery.
Link to Abstract:
https://clinicaltrials.gov/ct2/show/study/NCT00430989?recrs=e&cond=Heart&phase=23&lupd_s=01%2F01%2F2019&lupd_e=11%2F15%2F2021&draw=3
The goal of this study was to see if nitrous oxide (N2O) anaesthesia was safe in patients who had risk factors for coronary artery disease and were having major surgery.
Description in detail:
Around 25% of individuals undergoing major surgery had known coronary artery disease (CAD) or CAD risk factors.
The metabolism of vitamin B12 and folate is disrupted by N2O. This reduces the creation of methionine (from homocysteine), which is required for the synthesis of tetrahydrofolate and thymidine in DNA. N2O anaesthesia has been shown to raise postoperative homocysteine levels on numerous occasions. Acute hyperhomocysteinaemia is known to produce endothelial dysfunction, and chronic hyperhomocysteinaemia is linked to cardiovascular disease. In one short study, patients who had N2O anaesthesia had a higher rate of postoperative myocardial ischaemia. For people with CAD who are having major surgery, reducing postoperative myocardial infarction and death are key goals.
Our earlier study (ENIGMA) looked at 2050 patients and found some major side effects, but because most of them were not at risk of CAD, we couldn't properly quantify serious cardiac problems. To offer a definitive evaluation of the safety of N2O anesthesia, we suggest a large simple randomized clinical trial with 7,000 patients.
Professor Paul Myles, MD is the current Director of Anaesthesia and Perioperative Medicine at the Alfred and the Chair of the Academic Board of Anaesthesia and Perioperative Medicine. Professor Myles is also a Fellow of the Australian Academy of Health and Medical Sciences and an Australian NHMRC Practitioner Fellow. In this video Dr. Myles speaks about The ENIGMA II Trial: Nitrous Oxide Anesthesia and Cardiac Morbidity After Major Surgery.
Link to Abstract:
https://clinicaltrials.gov/ct2/show/study/NCT00430989?recrs=e&cond=Heart&phase=23&lupd_s=01%2F01%2F2019&lupd_e=11%2F15%2F2021&draw=3
The goal of this study was to see if nitrous oxide (N2O) anaesthesia was safe in patients who had risk factors for coronary artery disease and were having major surgery.
Description in detail:
Around 25% of individuals undergoing major surgery had known coronary artery disease (CAD) or CAD risk factors.
The metabolism of vitamin B12 and folate is disrupted by N2O. This reduces the creation of methionine (from homocysteine), which is required for the synthesis of tetrahydrofolate and thymidine in DNA. N2O anaesthesia has been shown to raise postoperative homocysteine levels on numerous occasions. Acute hyperhomocysteinaemia is known to produce endothelial dysfunction, and chronic hyperhomocysteinaemia is linked to cardiovascular disease. In one short study, patients who had N2O anaesthesia had a higher rate of postoperative myocardial ischaemia. For people with CAD who are having major surgery, reducing postoperative myocardial infarction and death are key goals.
Our earlier study (ENIGMA) looked at 2050 patients and found some major side effects, but because most of them were not at risk of CAD, we couldn't properly quantify serious cardiac problems. To offer a definitive evaluation of the safety of N2O anaesthesia, we suggest a large simple randomized clinical trial with 7,000 patients.
Renal Denervation Combined Carotid and Coronary Artery Disease and Critical Limb Ischemia
Integration of Rubidium-82 PET Derived Regional MBF Quantification in the Diagnosis of CAD
Morten Krogh Christiansen, MD, Department of Cardiology, Aarhus University Hospital, Aarhus, Denmark speaks about Polygenic Risk Score–Enhanced Risk Stratification of Coronary Artery Disease in Patients With Stable Chest Pain.
Link to AHA Article:
https://www.ahajournals.org/doi/abs/10.1161/CIRCGEN.120.003298
Summary -
Backstory:
Although polygenic risk scores (PRSs) have been linked to coronary artery disease (CAD), the therapeutic utility of utilizing PRSs for risk stratification at the single-patient level has yet to be determined. We wanted to see if adding a PRS to clinical risk factors (CRFs) improved risk classification in individuals who were referred for coronary computed tomography angiography because they were suspected of having obstructive CAD.
Methodologies:
We recruited 1617 patients with stable chest symptoms and no history of CAD who were referred for coronary computed tomography angiography in this prespecified diagnostic substudy of the Dan-NICAD trial (Danish study of Non-Invasive testing in Coronary Artery Disease). Age, sex, symptoms, past or active smoking, antihypertensive medication, lipid-lowering treatment, and diabetes were all utilized as CRFs for risk classification. Patients' genotypes were also determined, as well as their PRSs. A coronary computed CT angiography was performed on all of the patients. Invasive coronary angiography with fractional flow reserve was also performed on patients suspected of having a 50% stenosis. Visual invasive coronary angiography stenosis >90%, fractional flow reserve 0.80, or quantitative coronary analysis stenosis >50% if fractional flow reserve measurements were not possible were used to establish a combined endpoint of obstructive CAD.
Outcomes:
Independent of CRFs, the PRS was linked to obstructive CAD (adjusted odds ratio, 1.8 [95 percent CI, 1.5–2.2] per SD). The PRS showed a 0.63 (0.59–0.68) area under the curve, which was similar to that of age and sex. When the PRS and CRFs were combined, the CRF+PRS model had an AUC of 0.75 (0.71–0.79), which was 0.04 higher than the CRF model (P=0.0029). The use of pretest probability (pretest probability) cutoffs of 5% and 15% resulted in a net reclassification improvement of 15.8% (P=3.1104), with a down-classification of risk in 24 percent of patients (211 of 862) who had a pretest probability of 5% to 15% based on CRFs alone.
Findings:
Beyond CRFs, adding a PRS enhanced risk classification of obstructive CAD, indicating that PRSs might be used to guide diagnostic testing in the modern clinical context.