This study sought to assess whether the frequency of inducible myocardial ischemia during stress-rest single-photon emission computed tomography (SPECT) myocardial perfusion imaging (MPI) has changed ...over time.
The prevalence of cardiac death and other clinical cardiac events have declined in recent decades, but heretofore no study has examined if there has been a temporal change in the frequency of inducible myocardial ischemia during cardiac stress testing.
We assessed 39,515 diagnostic patients undergoing stress-rest MPI between 1991 and 2009. Patients were assessed for change in demographics, clinical symptoms, risk factors, and frequency of abnormal and ischemic SPECT-MPI.
There was a marked progressive decline in the prevalence of abnormal SPECT studies, from 40.9% in 1991 to 8.7% in 2009 (p < 0.001). Similarly, the prevalence of ischemic SPECT-MPI declined, from 29.6% to 5.0% (p < 0.001), as did the prevalence of severe ischemia. The decline of SPECT-MPI abnormality occurred among all age and symptom subgroups, falling to only 2.9% among recent exercising patients without typical angina. We also noted a progressive trend toward performing more pharmacological rather than exercise stress in all age and weight groups, and pharmacological stress was more likely than exercise to be associated with SPECT-MPI abnormality (odds ratio: 1.43, 95% confidence interval: 1.3 to 1.5; p < 0.001).
Over the past 2 decades, the frequency and severity of abnormal stress SPECT-MPI studies has progressively decreased. Notably, the frequency of abnormal SPECT-MPI is now very low among exercising patients without typical angina. These findings suggest the need for developing more cost-effective strategies for the initial work-up of patients who are presently at low risk for manifesting inducible myocardial ischemia during cardiac imaging procedures.
Summary Background Cardiosphere-derived cells (CDCs) reduce scarring after myocardial infarction, increase viable myocardium, and boost cardiac function in preclinical models. We aimed to assess ...safety of such an approach in patients with left ventricular dysfunction after myocardial infarction. Methods In the prospective, randomised CArdiosphere-Derived aUtologous stem CElls to reverse ventricUlar dySfunction (CADUCEUS) trial, we enrolled patients 2–4 weeks after myocardial infarction (with left ventricular ejection fraction of 25–45%) at two medical centres in the USA. An independent data coordinating centre randomly allocated patients in a 2:1 ratio to receive CDCs or standard care. For patients assigned to receive CDCs, autologous cells grown from endomyocardial biopsy specimens were infused into the infarct-related artery 1·5–3 months after myocardial infarction. The primary endpoint was proportion of patients at 6 months who died due to ventricular tachycardia, ventricular fibrillation, or sudden unexpected death, or had myocardial infarction after cell infusion, new cardiac tumour formation on MRI, or a major adverse cardiac event (MACE; composite of death and hospital admission for heart failure or non-fatal recurrent myocardial infarction). We also assessed preliminary efficacy endpoints on MRI by 6 months. Data analysers were masked to group assignment. This study is registered with ClinicalTrials.gov , NCT00893360. Findings Between May 5, 2009, and Dec 16, 2010, we randomly allocated 31 eligible participants of whom 25 were included in a per-protocol analysis (17 to CDC group and eight to standard of care). Mean baseline left ventricular ejection fraction (LVEF) was 39% (SD 12) and scar occupied 24% (10) of left ventricular mass. Biopsy samples yielded prescribed cell doses within 36 days (SD 6). No complications were reported within 24 h of CDC infusion. By 6 months, no patients had died, developed cardiac tumours, or MACE in either group. Four patients (24%) in the CDC group had serious adverse events compared with one control (13%; p=1·00). Compared with controls at 6 months, MRI analysis of patients treated with CDCs showed reductions in scar mass (p=0·001), increases in viable heart mass (p=0·01) and regional contractility (p=0·02), and regional systolic wall thickening (p=0·015). However, changes in end-diastolic volume, end-systolic volume, and LVEF did not differ between groups by 6 months. Interpretation We show intracoronary infusion of autologous CDCs after myocardial infarction is safe, warranting the expansion of such therapy to phase 2 study. The unprecedented increases we noted in viable myocardium, which are consistent with therapeutic regeneration, merit further assessment of clinical outcomes. Funding US National Heart, Lung and Blood Institute and Cedars-Sinai Board of Governors Heart Stem Cell Center.
Although pre-revascularization ischaemia testing is recommended, the interaction between the extent of ischaemia and myocardial scar with performance of revascularization on patient survival is ...unclear.
We identified 13 969 patients who underwent adenosine or exercise stress SPECT myocardial perfusion scintigraphy (MPS). The percent myocardium ischaemic (%I) and fixed (%F) were calculated using 5 point/20-segment MPS scoring. Patients lost to follow-up (2.8%) were excluded leaving 13 555 patients 35% with history (Hx) of known coronary artery disease (CAD), 65% exercise stress, 61% male, age 66 ± 12. Follow-up was performed at 12-18 months for early revascularization and at >7 years for all-cause death (ACD) (mean follow-up 8.7 ± 3.3 years). All-cause death was modelled using Cox proportional hazards modelling adjusting for logistic-based propensity scores, MPS, revascularization, and baseline characteristics. During FU, 3893 ACD (29%, 3.3%/year) and 1226 early revascularizations (9.0%) occurred. After risk-adjustment, a three-way interaction was present between %I, early revascularization, and HxCAD, such that %I identified a survival benefit with early revascularization in patients without prior myocardial infarction (MI), whereas no such benefit was present in patients with prior MI (overall model χ(2)= 3932, P < 0.001; interaction P < 0.021). Further modelling revealed that after excluding patients with scar >10% total myocardium, %I identified a survival benefit in all patients.
In this large observational series with long-term follow-up, patients with significant ischaemia and without extensive scar were likely to realize a survival benefit from early revascularization. In contrast, the survival of patients with minimal ischaemia was superior with medical therapy without early revascularization.
We conducted a prospective randomized trial to compare the clinical impact of conventional risk factor modification to that associated with the addition of coronary artery calcium (CAC) scanning.
...Although CAC scanning predicts cardiac events, its impact on subsequent medical management and coronary artery disease risk is not known.
We assigned 2,137 volunteers to groups that either did undergo CAC scanning or did not undergo CAC scanning before risk factor counseling. The primary end point was 4-year change in coronary artery disease risk factors and Framingham Risk Score. We also compared the groups for differences in downstream medical resource utilization.
Compared with the no-scan group, the scan group showed a net favorable change in systolic blood pressure (p = 0.02), low-density lipoprotein cholesterol (p = 0.04), and waist circumference for those with increased abdominal girth (p = 0.01), and tendency to weight loss among overweight subjects (p = 0.07). While there was a mean rise in Framingham Risk Score (FRS) in the no-scan group, FRS remained static in the scan group (0.7 ± 5.1 vs. 0.002 ± 4.9, p = 0.003). Within the scan group, increasing baseline CAC score was associated with a dose-response improvement in systolic and diastolic blood pressure (p < 0.001), total cholesterol (p < 0.001), low-density lipoprotein cholesterol (p < 0.001), triglycerides (p < 0.001), weight (p < 0.001), and Framingham Risk Score (p = 0.003). Downstream medical testing and costs in the scan group were comparable to those of the no-scan group, balanced by lower and higher resource utilization for subjects with normal CAC scans and CAC scores ≥400, respectively.
Compared with no scanning, randomization to CAC scanning was associated with superior coronary artery disease risk factor control without increasing downstream medical testing. Further study of CAC scanning, including pre-specified treatment recommendations, to assess its impact of cardiovascular outcomes is warranted.
The mechanistic basis of the symptoms and signs of myocardial ischaemia in patients without obstructive coronary artery disease (CAD) and evidence of coronary microvascular dysfunction (CMD) is ...unclear. The aim of this study was to mechanistically test short-term late sodium current inhibition (ranolazine) in such subjects on angina, myocardial perfusion reserve index, and diastolic filling.
Randomized, double-blind, placebo-controlled, crossover, mechanistic trial in subjects with evidence of CMD invasive coronary reactivity testing or non-invasive cardiac magnetic resonance imaging myocardial perfusion reserve index (MPRI). Short-term oral ranolazine 500-1000 mg twice daily for 2 weeks vs. placebo. Angina measured by Seattle Angina Questionnaire (SAQ) and SAQ-7 (co-primaries), diary angina (secondary), stress MPRI, diastolic filling, quality of life (QoL). Of 128 (96% women) subjects, no treatment differences in the outcomes were observed. Peak heart rate was lower during pharmacological stress during ranolazine (-3.55 b.p.m., P < 0.001). The change in SAQ-7 directly correlated with the change in MPRI (correlation 0.25, P = 0.005). The change in MPRI predicted the change in SAQ QoL, adjusted for body mass index (BMI), prior myocardial infarction, and site (P = 0.0032). Low coronary flow reserve (CFR <2.5) subjects improved MPRI (P < 0.0137), SAQ angina frequency (P = 0.027), and SAQ-7 (P = 0.041).
In this mechanistic trial among symptomatic subjects, no obstructive CAD, short-term late sodium current inhibition was not generally effective for SAQ angina. Angina and myocardial perfusion reserve changes were related, supporting the notion that strategies to improve ischaemia should be tested in these subjects.
clinicaltrials.gov Identifier: NCT01342029.
Women with coronary microvascular dysfunction (CMD) and no obstructive coronary artery disease (CAD) have increased rates of heart failure with preserved ejection fraction (HFpEF). The mechanisms of ...HFpEF are not well understood. Ectopic fat deposition in the myocardium, termed myocardial steatosis, is frequently associated with diastolic dysfunction in other metabolic diseases. We investigated the prevalence of myocardial steatosis and diastolic dysfunction in women with CMD and subclinical HFpEF. In 13 women, including eight reference controls and five women with CMD and evidence of subclinical HFpEF (left ventricular end-diastolic pressure >12 mmHg), we measured myocardial triglyceride content (TG) and diastolic function, by proton magnetic resonance spectroscopy and magnetic resonance tissue tagging, respectively. When compared with reference controls, women with CMD had higher myocardial TG content (0.83 ± 0.12% vs. 0.43 ± 0.06%; P = 0.025) and lower diastolic circumferential strain rate (168 ± 12 vs. 217 ± 15%/s; P = 0.012), with myocardial TG content correlating inversely with diastolic circumferential strain rate (r = -0.779; P = 0.002). This study provides proof-of-concept that myocardial steatosis may play an important mechanistic role in the development of diastolic dysfunction in women with CMD and no obstructive CAD. Detailed longitudinal studies are warranted to explore specific treatment strategies targeting myocardial steatosis and its effect on diastolic function.
Abstract Objective Epicardial fat volume (EFV) is related to calcified coronary plaques. However, it is unknown whether baseline EFV or changes in EFV affect the progression of coronary artery ...calcification over time. Methods We identified 375 consecutive asymptomatic subjects with an intermediate risk of developing coronary artery disease, who underwent serial non-contrast CT at least 3–5 years apart. Subjects were divided into tertiles of CCS progression (% increase) between the 2 scans. Subjects from the upper tertile (High Progressors) were matched by age and gender to 81 subjects from the lower tertile (Low Progressors). All subjects underwent serial measurements of CCS and EFV. Relationships between EFV and CCS progression, and change in plaque number were examined. Results At baseline, there was no difference in EFV, and EFV indexed to body surface area (EFVi) between the groups. At follow-up, EFV, EFVi and percent increase in EFVi-change were higher in High Progressors than Low Progressors (EFV, 102 ± 38 cm3 vs. 90 ± 35 cm3 , p = 0.03; EFVi, 50 ± 16 cm3 /m2 vs. 46 ± 15 cm3 /m2 , p = 0.03; percent increase in EFVi-change, 15 ± 22% vs. 7 ± 20%, p = 0.02). On multivariate analysis, after adjusting for conventional risk factors, EFVi increase ≥ 15% odds ratio (OR) 2.3, p < 0.05, log (baseline CCS) OR 0.3, p < 0.0001 and scan interval time p = 0.003, OR 1.0 were predictive of being a High Progressor. EFVi increase ≥ 15% ( β = 3.0, p = 0.02) and hypertension ( β = 3.1, p = 0.01) were independent predictors of number of new calcified plaques on follow-up. Conclusion Increase in EFV is associated with greater progression of coronary artery calcification in intermediate-risk subjects.
The goal of this study was to assess the clinical value of stress myocardial perfusion scintigraphy (MPS) in elderly patients (> or =75 years of age).
We followed up 5200 elderly patients (41% ...exercise) after dual-isotope MPS over 2.8+/-1.7 years (362 cardiac deaths CDs, 7.0%, 2.6%/y) and a subset with extended follow-up (684 patients for 6.2+/-2.9 years; 320 all-cause deaths). Survival modeling of CD revealed that both MPS-measured ischemia and fixed defect added incrementally to pre-MPS data in both adenosine and exercise stress patients. Modeling a subset with gated MPS (n=2472) revealed that ejection fraction and perfusion data added incrementally to each other, further enhancing risk stratification. Unadjusted, annualized post-normal MPS CD rate was 1.3% but <1% in patients with normal rest ECG, exercise stress, or age of 75 to 84 years and was 2.3% to 3.7% in patients > or =85 years of age or undergoing pharmacological stress. However, compared with age-matched US population CD rates (75 to 84 years of age, 1.5%; > or =85 years, 4.8%), normal MPS CD rates were approximately one-third lower than the baseline risk of US individuals (both P<0.05). Modeling of all-cause death in 684 patients with extended follow-up revealed that after risk adjustment, an interaction between early treatment and ischemia was present; increasing ischemia was associated with increasing survival with early revascularization, whereas in the setting of little or no ischemia, medical therapy had improved outcomes.
Stress MPS effectively stratifies CD risk in elderly patients and may identify optimal post-MPS therapy. CD rates after normal MPS are low in all subsets in relative terms compared with the age-matched US population.
Adverse health behaviors are potent drivers of chronic disease and premature mortality. This has led to the development of various lifestyle scores to predict clinical risk, but their complexity ...makes them impractical for use in clinical settings. Thus, there is a need to develop a brief lifestyle score that can assess factors such as exercise and diet within the constraints of routine medical practice. Accordingly, we assessed 19,081 patients undergoing coronary artery calcium (CAC) scanning between September 1, 1998 and December 30, 2016. Each patient completed a questionnaire that included a two-item lifestyle scale regarding patients’ frequency of exercise and adherence to a low saturated fat diet. Patients’ responses were used to generate a lifestyle score which ranged from very low risk to high risk. Patients were followed for a median of 11.0 years for all-cause mortality. A stepwise relationship was noted between worse lifestyle scores and increased frequency of hypertension, diabetes, smoking, obesity, waist/hip ratio, and resting heart rate and blood pressure. Among patients with zero CAC scores, mortality risk was low regardless of lifestyle score, but as CAC abnormality increased, a stepwise relationship emerged between worse lifestyle scores and mortality. The lifestyle score was more predictive of mortality than conventional CAD risk factors according to multivariable Chi-square analysis. Thus, our results establish the practicality of an ultrashort lifestyle questionnaire that could be employed in nearly all clinical settings. Within our study, our two-item lifestyle scale showed a stepwise relationship to known CAD risk factors and predicted future mortality.
PDF
