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.
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.
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.
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.
This study examined short-term cardiac catheterization rates and medication changes after cardiac imaging.
Noninvasive cardiac imaging is widely used in coronary artery disease, but its effects on ...subsequent patient management are unclear.
We assessed the 90-day post-test rates of catheterization and medication changes in a prospective registry of 1,703 patients without a documented history of coronary artery disease and an intermediate to high likelihood of coronary artery disease undergoing cardiac single-photon emission computed tomography, positron emission tomography, or 64-slice coronary computed tomography angiography.
Baseline medication use was relatively infrequent. At 90 days, 9.6% of patients underwent catheterization. The rates of catheterization and medication changes increased in proportion to test abnormality findings. Among patients with the most severe test result findings, 38% to 61% were not referred to catheterization, 20% to 30% were not receiving aspirin, 35% to 44% were not receiving a beta-blocker, and 20% to 25% were not receiving a lipid-lowering agent at 90 days after the index test. Risk-adjusted analyses revealed that compared with stress single-photon emission computed tomography or positron emission tomography, changes in aspirin and lipid-lowering agent use was greater after computed tomography angiography, as was the 90-day catheterization referral rate in the setting of normal/nonobstructive and mildly abnormal test results.
Overall, noninvasive testing had only a modest impact on clinical management of patients referred for clinical testing. Although post-imaging use of cardiac catheterization and medical therapy increased in proportion to the degree of abnormality findings, the frequency of catheterization and medication change suggests possible undertreatment of higher risk patients. Patients were more likely to undergo cardiac catheterization after computed tomography angiography than after single-photon emission computed tomography or positron emission tomography after normal/nonobstructive and mildly abnormal study findings. (Study of Perfusion and Anatomy's Role in Coronary Artery CAD SPARC; NCT00321399).
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.
To evaluate temporal trends in the prevalence of typical angina and its clinical correlates among patients referred for stress/rest SPECT myocardial perfusion imaging (MPI).
We evaluated the ...prevalence of chest pain symptoms and their relationship to inducible myocardial ischemia among 61,717 patients undergoing stress/rest SPECT-MPI between January 2, 1991 and December 31, 2017. We also assessed the relationship between chest pain symptom and angiographic findings among 6,579 patients undergoing coronary CT angiography between 2011 and 2017.
The prevalence of typical angina among SPECT-MPI patients declined from 16.2% between 1991 and 1997 to 3.1% between 2011 and 2017, while the prevalence of dyspnea without any chest pain increased from 5.9 to 14.5% over the same period. The frequency of inducible myocardial ischemia declined over time within all symptom groups, but its frequency among current patients (2011–2017) with typical angina was approximately three-fold higher versus other symptom groups (28.4% versus 8.6%, p < 0.001). Overall, patients with typical angina had a higher prevalence of obstructive CAD on CCTA than those with other clinical symptoms, but 33.3% of typical angina patients had no coronary stenoses, 31.1% had 1–49% stenoses, and 35.4% had ≥ 50% stenoses.
The prevalence of typical angina has declined to a very low level among contemporary patients referred for noninvasive cardiac tests. The angiographic findings among current typical angina patients are now quite heterogeneous, with one-third of such patients having normal coronary angiograms. However, typical angina remains associated with a substantially higher frequency of inducible myocardial ischemia compared to patients with other cardiac symptoms.
Evaluar las tendencias temporales en la prevalencia de la angina típica y su correlación clínica entre pacientes referidos estudio de perfusión miocárdica SPECT de estrés/reposo (MPI). Pacientes y métodos. Se evaluó la prevalencia de síntomas de dolor torácico y su relación con la isquemia miocárdica inducible en 61,717 pacientes sometidos a SPECT-MPI de estrés/reposo entre el 2 de enero de 1991 y el 31 de diciembre de 2017. También evaluamos la relación entre el síntoma de dolor torácico y los hallazgos angiográficos en 6,579 pacientes sometidos a angiografía coronaria por TC entre 2011–2017.
La prevalencia de angina típica entre los pacientes con SPECT-MPI disminuyó de 16.2% entre 1991–1997 a 3.1% entre 2011–2017, mientras que la prevalencia de disnea sin dolor torácico aumentó del 5.9% al 14.5% durante el mismo período. La frecuencia de isquemia miocárdica inducible disminuyó con el tiempo dentro de todos los grupos con síntomas pero su frecuencia entre los pacientes actuales (2011–2017) con angina típica fue aproximadamente tres veces mayor que otros grupos de síntomas (28.4% frente a 8.6%, p < 0.001). En general, los pacientes con angina típica tenían una mayor prevalencia de enfermedad arterial coronaria obstructiva en la angiografía coronaria por TC que aquellos con otros síntomas clínicos, pero el 33.3% de los pacientes con angina típica no tenían estenosis coronaria, el 31.1% tenía estenosis del 1–49% y el 35.4% tenía estenosis > 50%.
La prevalencia de angina típica ha disminuido a un nivel muy bajo entre pacientes contemporáneos referidos para pruebas cardíacas no invasivas. Los hallazgos angiográficos entre los pacientes actuales con angina típica son bastante heterogéneos, con un tercio de estos pacientes con angiogramas coronarios normales. Sin embargo, la angina típica permanece asociada con una frecuencia sustancialmente mayor de isquemia miocárdica inducible en comparación con pacientes con otros síntomas cardíacos.
通过负荷/静息核素心肌灌注显像检查, 评估患者的典型心绞痛发病率的时间趋势及其临床相关性。
我们评估了1991年1月2日至2017年12月31日之间61717名患者胸痛症状的发病率与可诱发心肌缺血之间的关系。所有患者均接受了负荷/静息放射性核素心肌灌注显像检查。 我们还评估了2011-2017年之间接受冠脉CTA的6579名患者胸痛症状与血管造影结果的关系。
在SPECT-MPI患者中, 典型心绞痛的发病率从1991-1997年的16.2%下降到2011-2017年的3.1%, 而在同一时期, 无胸痛的呼吸困难的发病率从5.9%上升到14.5%。在所有症状组中, 诱发性心肌缺血的频率随时间而下降; 但在(2011-2017年) 典型心绞痛的患者中, 诱发心肌缺血频率约为其他症状组的三倍 (28.4% vs 8.6%, p < 0.001) 。总体上, 冠脉CTA出现狭窄的冠心病患者中, 典型心绞痛发病率更高; 但在典型心绞痛患者中, 33.3%的患者冠状动脉无狭窄, 31.1%的患者狭窄程度在1 ~ 49%, 35.4%的患者狭窄程度 ≥ 50%。
在接受非侵入性心脏检查的患者中, 目前典型心绞痛的发病率已降至非常低的水平。在典型心绞痛患者中, 血管造影结果差异很大, 其中三分之一的患者冠脉造影结果正常。然而, 与其他心脏症状的患者相比, 典型心绞痛仍然与更高频率可诱发的心肌缺血有关。
Évaluer les tendances temporelles dans la prévalence de l’angine typique et ses corrélats cliniques parmi les patients référés pour des études d’imagerie de perfusion myocardique effort/repos en SPECT (IPM).
Nous avons évalué la prévalence des symptômes de douleur thoracique et leur relation à l’ischémie myocardique induite chez 61,717 patients ayant eu une IPM entre le 2 janvier 1991 et le 31 décembre 2017. Nous avons également évalué la relation entre le symptôme de douleur thoracique et les résultats angiographiques parmi 6,579 patients ayant eu un angioscan CT coronarien (ACTC) entre 2011 et 2017.
La prévalence d’angine typique parmi les patients avec une IPM a diminué de 16.2% entre 1991–1997 a 3.1% entre 2011–2017, tandis que la prévalence de la dyspnée sans aucune douleur thoracique a augmenté de 5.9% à 14.5% sur cette même période. La fréquence d’ischémie myocardique inductible a décliné chez tous les groupes de symptômes mais sa fréquence parmi les patients actuels (2011–2017) avec angine typique était approximativement trois fois plus élevée par rapport aux autres groupes de symptômes (28.4% versus 8.6%, p 0.001). Dans l’ensemble, les patients avec de l’angine typique avaient une prévalence plus élevée de MCAS obstructive sur ACTC que ceux des autres symptômes cliniques, mais 33.3% des patients avec angine typique n’avaient pas de sténoses coronariennes, 31.1% avaient des sténoses entre 1–49% et 35.4% avaient des sténoses de plus de 50%.
La prévalence d’angine typique a diminué à de très bas niveaux parmi les patients contemporains référés pour des tests cardiaques noneffractifs. Les résultats angiographiques parmi les patients actuels avec angine typique sont maintenant plus hétérogènes, avec un tiers de ces patients ayant une angiographie coronarienne normale. L’angine typique demeure cependant associée à une fréquence substantiellement plus élevée d’ischémie myocardique inductible comparativement aux patients ayant d’autres symptômes cardiaques.
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