Precision medicine: Hype or hope?

In recent years, precision medicine has steadily risen to the forefront of many aspects of medicine, including cardiology [1]. While this field has exponentially expanded and advanced in the last few years, a lot of questions remain regarding exact definition, usage, and clinical applications [2,3]. This review will provide a brief synopsis of the current state of precision medicine, its limitations, future directions, as well as analyze emerging clinical applications in cardiology.

Innovation in Cardiology: The ACC Innovation Program.

The last half century has seen extraordinary advances in the field of cardiology, including innovations in medications, diagnostic modalities, and therapeutics. Even so, cardiovascular disease remains the leading cause of morbidity and mortality globally, with suboptimal quality of care, inconsistent health outcomes, and unsustainable costs. It is clear that cardiovascular medicine must undergo a digital transformation to enhance the delivery of quality care and to improve outcomes. To meet this need, the American College of Cardiology developed an innovation program focused on the digital transformation of cardiovascular care, with the goal of improving heart health for individuals and populations.

Comparative efficiency of exercise stress testing with and without stress-only myocardial perfusion imaging in patients with low-risk chest pain.

OBJECTIVES: To compare major adverse cardiac event (MACE), downstream resource utilization, and direct cost of care for low-risk chest pain patients observed in the clinical decision unit (CDU) with exercise treadmill testing (ETT) and with stress-only myocardial perfusion imaging (sMPI). BACKGROUND: CDUs are poised to increase efficiency and resource utilization. However, the optimal testing strategy that would assure favorable outcomes while decreasing cost is not defined. METHODS: 1016 subjects from 2 locations were propensity score-matched (PSM) by age, gender, pre-test likelihood, Duke treadmill score, and test results. Outcomes were length of stay >24 hours, MACE (acute coronary syndrome, revascularization, cardiac death), downstream resource use (admission for chest pain, repeat testing, angiography), and mean direct cost per patient. RESULTS: PSM yielded 680 patients (340 matches). 98% of all tests were normal. 96.6% of patients were discharged from the CDU within 24 hours but twice as many exceeded 24 hours in the sMPI group. There were no cardiac deaths. MACE rate was 1.47% at 72 hours and 1% at 1 year. Downstream resource use was 4.82% at 72 hours, and 7.69% at 1 year. The sMPI group was event-free longer than the ETT group reflecting less repeat testing. The mean direct cost was 30% higher for sMPI ($3168.70) vs. ETT ($2226.96). CONCLUSION: Low-risk chest pain patients in the observation unit had low MACE rate, not different for ETT vs. sMPI. The majority of ETT and sMPI tests were normal. The sMPI reduced additional testing, but resulted in greater expense and longer stay.

Downstream resource utilization following SPECT: Impact of age and gender.

BACKGROUND: Previous studies have identified a downstream referral age and gender bias for invasive coronary anatomy evaluation after single-photon emission computed tomography myocardial perfusion imaging (SPECT MPI). The present study evaluates if such bias still persists despite advancements in SPECT MPI and angiography. We hypothesized that women and patients ≥80 years old are less likely to undergo invasive coronary angiography after adjusting for clinical and scan variables. METHODS: Patients (n = 3824) who referred to a nuclear cardiology laboratory at a tertiary medical center were retrospectively identified. Regression analysis tested age (<55; 55-69; 70-79; ≥80 years) and gender as predictors of diagnostic angiogram at 90 days post-SPECT after adjustment for known CAD, CAD risk equivalent, SSS, SDS, and LVEF. RESULTS: Younger patients were more likely to undergo an angiogram as compared to octogenarians (77% more likely if <55 years old, 69% if 55-69 years old, and 52% if 70-79 years old). No effect was found for gender. CONCLUSIONS: Older patients were less likely to be referred for angiogram as compared to their younger counterparts. Further study is needed to determine which factors guide this decision-making process in older adults and the influence of these factors on the referral bias.

Noninvasive Cardiovascular Risk Assessment of the Asymptomatic Diabetic Patient: The Imaging Council of the American College of Cardiology.

Increased cardiovascular morbidity and mortality in patients with type 2 diabetes is well established; diabetes is associated with at least a 2-fold increased risk of coronary heart disease. Approximately two-thirds of deaths among persons with diabetes are related to cardiovascular disease. Previously, diabetes was regarded as a "coronary risk equivalent," implying a high 10-year cardiovascular risk for every diabetes patient. Following the original study by Haffner et al., multiple studies from different cohorts provided varying conclusions on the validity of the concept of coronary risk equivalency in patients with diabetes. New guidelines have started to acknowledge the heterogeneity in risk and include different treatment recommendations for diabetic patients without other risk factors who are considered to be at lower risk. Furthermore, guidelines have suggested that further risk stratification in patients with diabetes is warranted before universal treatment. The Imaging Council of the American College of Cardiology systematically reviewed all modalities commonly used for risk stratification in persons with diabetes mellitus and summarized the data and recommendations. This document reviews the evidence regarding the use of noninvasive testing to stratify asymptomatic patients with diabetes with regard to coronary heart disease risk and develops an algorithm for screening based on available data.

Clinical evaluation of the appropriateness use criteria for single-photon emission-computed tomography: differences by patient population, physician specialty, and patient outcomes.

Objectives. Determine outcome of the 2005 appropriateness use criteria (AUC) for SPECT in a diverse population of patients and physicians. Background. AUC for SPECT were the first cardiology document to identify 52 clinical indications for imaging, 49 of them for stress SPECT. AUC have been proposed as cornerstone of responsible use of perfusion imaging. Methods. 585 consecutive patients undergoing SPECT were evaluated prospectively. Appropriateness was examined for demographic variables, clinical variables, and for physician and patient subgroups. Combined end-point of total mortality, cardiac revascularization, and cardiac admissions at 1 year post SPECT was evaluated. Results. SPECT indications were: appropriate, 63%; uncertain, 20%; inappropriate, 14%; not assigned, 3%. Most appropriate SPECT were observed in patients with known coronary disease (72%), chest pain syndrome (89%), high pre-test likelihood of disease (100%), men (70%), inpatients (72%), and cardiovascular physicians' referrals (69%). End-point was reached in 53 patients (97.4% follow up). Unadjusted event rates were: appropriate (12%), uncertain (7.1%), inappropriate (2.4%) SPECT (P = .01). Conclusion. Appropriateness of SPECT differs in subgroups of patients and physicians. Clinically significant outcomes occur more frequently in the appropriate stress SPECT group. Focused efforts are need for outpatients, asymptomatic patients, women, and non-cardiovascular physicians.

Wide-beam reconstruction half-time SPECT improves diagnostic certainty and preserves normalcy and accuracy: a quantitative perfusion analysis.

BACKGROUND: Filtered back-projection (FBP) has been a standard in SPECT imaging. Newer iterative reconstruction algorithms have been shown to improve image quality and shorten acquisition time by taking into account statistical nature of raw data and using resolution recovery (RR). Wide-beam reconstruction (WBR) is an iterative algorithm with RR and adaptive noise control. We prospectively investigated outcome of WBR half-time SPECT on diagnostic certainty, accuracy and normalcy by quantitative perfusion analysis in comparison to full-time FBP images. METHODS: 434 patients underwent rest (201)Tl/stress (99m)Tc-sestamibi full-time (20 s/stop, FBP) followed by a half-time (10 s/stop, WBR) SPECT. 34 patients underwent an angiogram within 90 days of SPECT. Diagnostic certainty was based on summed stress scores (SSS, 5-point/17 segments): normal if SSS ≤ 1, equivocal if SSS = 2-3, and abnormal if SSS ≥ 4. Perfusion defects were normalized to a percent of total myocardium, and expressed as %LV = defect SSS/maximal SSS × 100% with maximal SSS of 28 for left anterior descending (LAD), and of 20 for right coronary (RCA) and left circumflex (LCX). Change in %LV (Δ%LV = %LV FBP - %LV WBR) was evaluated for diagnostically discordant versus concordant scans. RESULTS: SSS and %LV demonstrated very good correlation. There were significantly fewer equivocal scans with WBR (38 vs 151 FBP, P < .0001). Most discordant scans were equivocal FBP SPECT becoming normal with WBR (123/151). Δ%LV(LAD) for discordant studies was greater for women (5.4% ± 4.2%, P < .001), while Δ%LV(RCA,LCX) (4.4% ± 5.1%, P < .001; 1.2% ± 5.0%, P = .04) were greater for men. Normalcy rate was 91.4% for FBP and WBR with more definitely normal WBR studies (84.5% vs 43.9% for FBP, P < .0001). There were no differences in sensitivity (FBP 84.2%, WBR 81.6%), specificity (FBP 54.6%, WBR 63.6%), and accuracy (FBP, WBR 77.6%). CONCLUSION: Quantitative perfusion analysis suggests that adaptive noise control with WBR improves uniformity of myocardium comparing to FBP techniques, and results in improved diagnostic certainty while preserving normalcy and accuracy.

Current advances in vasodilator pharmacological stress perfusion imaging.

More than 7 million stress perfusion studies are performed in the United States annually, 44% with pharmacological vasodilator stress agents. Both adenosine and dipyridamole are nonselective coronary vasodilators that are commonly used for stress perfusion imaging. These agents are safe and provide an effective means to diagnose coronary artery disease. A newer agent, regadenoson, is an adenosine receptor agonist that is selective for coronary vasodilation. Regadenoson is noninferior to adenosine for the detection of ischemia and is better tolerated by patients. Recent trials such as INSPIRE (Adenosine Sestamibi Post-Infarction Evaluation) and the COURAGE (Results from Clinical Outcomes Utilizing Revascularization and Aggressive Guideline-driven Drug Evaluation) Nuclear Imaging Substudy have established clearly that noninvasive risk stratification with vasodilator testing is an important and appropriate step in guiding medical therapy and invasive coronary intervention.

Postischemic stunning after adenosine vasodilator stress.

BACKGROUND: Ischemic left ventricular (LV) dysfunction may occur after exercise but is regarded as uncommon after vasodilator stress. We evaluated the prevalence of LV dysfunction after adenosine stress in relation to reversible perfusion defects and angiographic coronary artery disease (CAD). METHODS AND RESULTS: We studied 86 patients referred for clinically indicated adenosine dual-isotope gated single photon emission computed tomography: 43 with 1 or more reversible perfusion defects (reversible defect group) and 43 age- and sex-matched patients with no known CAD and normal LV perfusion and function (control group). Coronary angiography was performed in 36 of 43 patients (84%) in the reversible defect group. Perfusion was interpreted based on 20-segment/5-point summed rest and stress scores. The extent of reversibility was defined by the summed difference score. LV ejection fraction and volumes at rest and 60 minutes after adenosine and segmental wall thickening were quantified by QGS (Cedars-Sinai Medical Center, Los Angeles, Calif). In patients with extensive reversible perfusion defects (summed difference score > or =8), 8 of 25 (32%) demonstrated depressed post-adenosine LV ejection fraction, abnormal segmental wall thickening, end-systolic dilation, and extensive CAD. CONCLUSION: Adenosine is believed to be less likely than exercise to induce ischemia. However, myocardial stunning occurred in one third of the patients with severe reversible defects, consistent with ischemia.