IMPROvE-CED Trial: Intracoronary Autologous CD34+ Cell Therapy for Treatment of Coronary Endothelial Dysfunction in Patients With Angina and Nonobstructive Coronary Arteries.

BACKGROUND: Coronary endothelial dysfunction (CED) causes angina/ischemia in patients with nonobstructive coronary artery disease (NOCAD). Patients with CED have decreased number and function of CD34+ cells involved in normal vascular repair with microcirculatory regenerative potential and paracrine anti-inflammatory effects. We evaluated safety and potential efficacy of intracoronary autologous CD34+ cell therapy for CED. METHODS: Twenty NOCAD patients with invasively diagnosed CED and persistent angina despite maximally tolerated medical therapy underwent baseline exercise stress test, GCSF (granulocyte colony stimulating factor)-mediated CD34+ cell mobilization, leukapheresis, and selective 1×105 CD34+ cells/kg infusion into left anterior descending. Invasive CED evaluation and exercise stress test were repeated 6 months after cell infusion. Primary end points were safety and effect of intracoronary autologous CD34+ cell therapy on CED at 6 months of follow-up. Secondary end points were change in Canadian Cardiovascular Society angina class, as-needed sublingual nitroglycerin use/day, Seattle Angina Questionnaire scores, and exercise time at 6 months. Change in CED was compared with that of 51 historic control NOCAD patients treated with maximally tolerated medical therapy alone. RESULTS: Mean age was 52±13 years; 75% were women. No death, myocardial infarction, or stroke occurred. Intracoronary CD34+ cell infusion improved microvascular CED (%acetylcholine-mediated coronary blood flow increased from 7.2 [-18.0 to 32.4] to 57.6 [16.3-98.3]%; P=0.014), decreased Canadian Cardiovascular Society angina class (3.7±0.5 to 1.7±0.9, Wilcoxon signed-rank test, P=0.00018), and sublingual nitroglycerin use/day (1 [0.4-3.5] to 0 [0-1], Wilcoxon signed-rank test, P=0.00047), and improved all Seattle Angina Questionnaire scores with no significant change in exercise time at 6 months of follow-up. Historic control patients had no significant change in CED. CONCLUSIONS: A single intracoronary autologous CD34+ cell infusion was safe and may potentially be an effective disease-modifying therapy for microvascular CED in humans. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03471611.

Cardiogenic shock complicating non-ST-segment elevation myocardial infarction: An 18-year study.

OBJECTIVE: To evaluate the epidemiology and outcomes of non-ST-segment-elevation myocardial infarction-cardiogenic shock (NSTEMI-CS) in the United States. METHODS: Adult (>18 years) NSTEMI-CS admissions were identified using the National Inpatient Sample (2000-2017) and classified by tertiles of admission year (2000-2005, 2006-2011 and 2012-2017). Outcomes of interest included temporal trends of prevalence and in-hospital mortality, use of cardiac procedures, in-hospital mortality, hospitalization costs, and length of stay. RESULTS: In over 7.3 million NSTEMI admissions, CS was noted in 189,155 (2.6%). NSTEMI-CS increased from 1.5% in 2000 to 3.6% in 2017 (adjusted odds ratio 2.03 [95% confidence interval 1.97-2.09]; P < .001). Rates of non-cardiac organ failure and cardiac arrest increased during the study period. Between 2000 and 2017, coronary angiography (43.9%-63.9%), early coronary angiography (13.6%-25.6%), percutaneous coronary intervention (14.8%-31.6%), and coronary artery bypass grafting use (19.0%-25.8%) increased (P < .001). Over the study period, the use of intra-aortic balloon pump remained stable (28.6%-28.8%), and both percutaneous left ventricular assist devices (0%-9.1%) and extra-corporeal membrane oxygenation (0.1%-1.6%) increased (all P < .001). In hospital mortality decreased from 50.2% in 2000 to 32.3% in 2017 (adjusted odds ratio 0.27 [95% confidence interval 0.25-0.29]; P < .001). During the 18-year period, hospital lengths of stay decreased, and hospitalization costs increased. CONCLUSIONS: In the United States, prevalence of CS in NSTEMI has increased 2-fold between 2000 and 2017, while in-hospital mortality has decreased during the study period. Use of coronary angiography and percutaneous coronary intervention increased during the study period.

Intravascular ultrasound, optical coherence tomography, and fractional flow reserve use in acute myocardial infarction.

BACKGROUND: There are limited data on the use of intravascular ultrasound (IVUS), optical coherence tomography (OCT), and fractional flow reserve (FFR) during acute myocardial infarction (AMI). OBJECTIVES: To assess the temporal trends of IVUS, OCT, and FFR use in AMI. METHODS: A retrospective cohort study from the National Inpatient Sample (2004-2014) was designed to include AMI admissions that received coronary angiography. Administrative codes were used to identify percutaneous coronary intervention (PCI), IVUS, OCT, and FFR. Outcomes included temporal trends, inhospital mortality and resource utilization stratified by IVUS, OCT, or FFR use. RESULTS: In 4,419,973 AMI admissions, IVUS, OCT, and FFR were used in 2.6%, 0.1%, and 0.6%, respectively. There was a 22-fold, 118-fold, and 33-fold adjusted increase in IVUS, OCT, and FFR use, respectively, in 2014 compared to the first year of use. Non-ST-elevation AMI presentation, male sex, private insurance coverage, admission to a large urban hospital, and absence of cardiac arrest and cardiogenic shock were associated with higher IVUS, OCT, or FFR use. PCI was performed in 83.2% of the IVUS, OCT, or FFR cohort compared to 64.2% of the control group (p < .001). The cohort with IVUS/OCT/FFR use had lower inhospital mortality (adjusted odds ratio 0.53 [95% confidence interval 0.50-0.56]), more frequent discharges to home (83.7% vs. 76.8%), shorter hospital stays (4.3 ± 4.4 vs. 5.0 ± 5.5 days) and higher hospitalization costs ($90,683 ± 74,093 vs. $74,671 ± 75,841). CONCLUSIONS: In AMI, the use of IVUS, OCT, and FFR has increased during 2004-2014. Significant patient and hospital-level disparities exist in the use of these technologies.

International Expert Consensus Document on Takotsubo Syndrome (Part II): Diagnostic Workup, Outcome, and Management.

The clinical expert consensus statement on takotsubo syndrome (TTS) part II focuses on the diagnostic workup, outcome, and management. The recommendations are based on interpretation of the limited clinical trial data currently available and experience of international TTS experts. It summarizes the diagnostic approach, which may facilitate correct and timely diagnosis. Furthermore, the document covers areas where controversies still exist in risk stratification and management of TTS. Based on available data the document provides recommendations on optimal care of such patients for practising physicians.

International Expert Consensus Document on Takotsubo Syndrome (Part I): Clinical Characteristics, Diagnostic Criteria, and Pathophysiology.

Takotsubo syndrome (TTS) is a poorly recognized heart disease that was initially regarded as a benign condition. Recently, it has been shown that TTS may be associated with severe clinical complications including death and that its prevalence is probably underestimated. Since current guidelines on TTS are lacking, it appears timely and important to provide an expert consensus statement on TTS. The clinical expert consensus document part I summarizes the current state of knowledge on clinical presentation and characteristics of TTS and agrees on controversies surrounding TTS such as nomenclature, different TTS types, role of coronary artery disease, and etiology. This consensus also proposes new diagnostic criteria based on current knowledge to improve diagnostic accuracy.

Percutaneous revascularization in patients treated with thoracic radiation for cancer.

OBJECTIVES: To assess coronary revascularization outcomes in patients with previous thoracic radiation therapy (XRT). BACKGROUND: Previous chest radiation has been reported to adversely affect long term survival in patients with coronary disease treated with percutaneous coronary interventions (PCI). METHODS: Retrospective, single center cohort study of patients previously treated with thoracic radiation and PCI. Patients were propensity matched against control patients without radiation undergoing revascularization during the same time period. RESULTS: We identified 116 patients with radiation followed by PCI (XRT-PCI group) and 408 controls. Acute procedural complications were similar between groups. There were no differences in all-cause and cardiac mortality between groups (all-cause mortality HR 1.31, P=.078; cardiac mortality 0.78, P=.49). CONCLUSION: Patients with prior thoracic radiation and coronary disease treated with PCI have similar procedural complications and long term mortality when compared to control subjects.

Acute Brain Diseases as Triggers for Stress Cardiomyopathy: Clinical Characteristics and Outcomes.

OBJECTIVE: To determine the clinical characteristics and outcomes of patients with neurogenic stress cardiomyopathy (NSC) among patients admitted to our neuroscience intensive care unit (NICU). METHODS: Following institutional review board approval, consecutive adult patients admitted to the NICU between 2009 and 2013 with definite and possible NSC were included. Data on patient demographics, baseline clinical information, cardiac function, and laboratory values were collected. Outcomes included length of stay, modified Rankin Scale (mRS) at discharge and long-term follow-up. Continuous variables were compared using a student's t test, and categorical variables were compared using a Chi-square test. RESULTS: Among 34 patients included in the study, the most common presenting symptom was dyspnea (17 patients, 50%). Subarachnoid hemorrhage (SAH) was the most common neurological inciting event (11 patients, 32.4%), but two-thirds of this cohort had other neurological triggers. The most common electrocardiogram changes were QT-interval prolongation (30 patients, 88.2%) and T-wave inversion (22 patients, 64.7%). The most common echocardiographic pattern was the apical variant (14 patients, 41.2%), and 26% of patients had right ventricular involvement (P = 0.03) which was a predictor of poor outcome along with inotropic support (P = 0.006). Functional outcome was poor (mRS > 3) in 53% of patients at discharge, but function improved over time in most survivors. CONCLUSIONS: NSC is most common after SAH, but can result from a wide spectrum of acute brain insults. Requirement of inotropic support was the strongest indicator of prognosis at last follow-up. Patients with NSC often have poor function at discharge but many improve over time.

Reduction of atherothrombotic burden before stent deployment in non-ST elevation acute coronary syndromes: Reduction of myocardial necrosis achieved with nose-dive manual thrombus aspiration (REMNANT) trial. A volumetric intravascular ultrasound study.

OBJECTIVES: To test whether thrombus aspiration (TA) reduces the atherosclerotic burden in culprit lesions and "facilitate" percutaneous coronary intervention with stent (S-PCI) among patients with non-ST elevation acute coronary syndromes (NSTE-ACS). BACKGROUND: Evidence on the effects of TA adjunctive to S-PCI in NSTE-ACS is limited and controversial. METHODS: TA was defined "aggressive" when using 7F devices or a catheter/artery ratio >0.6, "conservative" with 6F, and a catheter/artery ratio ≤0.6. Angiography and intravascular ultrasound (IVUS) were performed at baseline, after TA and after stent deployment. RESULTS: TA was accomplished in 61/76 patients (80%) with NSTE-ACS. The aspirated material was red thrombus in 23% and plaque fragments in 49% of cases. Compared with baseline, TA was associated with an 82% increase in minimal lumen diameter and a 15% reduction in diameter stenosis (P < 0.001 for both). After TA, IVUS documented a 24 and 16% increase in minimal lumen area and lumen volume, respectively (P < 0.001 for both), a 7% decrease in area stenosis through an 11% reduction of plaque + media volume (P < 0.001). When compared with "conservative", an "aggressive" TA was associated with a more pronounced reduction in percent area stenosis (P < 0.05) and an increase in percent stent expansion (P < 0.001). The plaque + media volume reduction after TA was correlated with stent expansion (r = 0.261, P = 0.046). CONCLUSIONS: Manual TA reduces atherothrombotic burden in culprit lesions of NSTE-ACS patients before S-PCI and, when deep plaque removal is obtained, TA optimizes subsequent stent expansion. © 2015 Wiley Periodicals, Inc.

Effect of Care Guided by Cardiovascular Magnetic Resonance, Myocardial Perfusion Scintigraphy, or NICE Guidelines on Subsequent Unnecessary Angiography Rates: The CE-MARC 2 Randomized Clinical Trial.

IMPORTANCE: Among patients with suspected coronary heart disease (CHD), rates of invasive angiography are considered too high. OBJECTIVE: To test the hypothesis that among patients with suspected CHD, cardiovascular magnetic resonance (CMR)-guided care is superior to National Institute for Health and Care Excellence (NICE) guidelines-directed care and myocardial perfusion scintigraphy (MPS)-guided care in reducing unnecessary angiography. DESIGN, SETTING, AND PARTICIPANTS: Multicenter, 3-parallel group, randomized clinical trial using a pragmatic comparative effectiveness design. From 6 UK hospitals, 1202 symptomatic patients with suspected CHD and a CHD pretest likelihood of 10% to 90% were recruited. First randomization was November 23, 2012; last 12-month follow-up was March 12, 2016. INTERVENTIONS: Patients were randomly assigned (240:481:481) to management according to UK NICE guidelines or to guided care based on the results of CMR or MPS testing. MAIN OUTCOMES AND MEASURES: The primary end point was protocol-defined unnecessary coronary angiography (normal fractional flow reserve >0.8 or quantitative coronary angiography [QCA] showing no percentage diameter stenosis ≥70% in 1 view or ≥50% in 2 orthogonal views in all coronary vessels ≥2.5 mm diameter) within 12 months. Secondary end points included positive angiography, major adverse cardiovascular events (MACEs), and procedural complications. RESULTS: Among 1202 symptomatic patients (mean age, 56.3 years [SD, 9.0]; women, 564 [46.9%] ; mean CHD pretest likelihood, 49.5% [SD, 23.8%]), number of patients with invasive coronary angiography after 12 months was 102 in the NICE guidelines group (42.5% [95% CI, 36.2%-49.0%])], 85 in the CMR group (17.7% [95% CI, 14.4%-21.4%]); and 78 in the MPS group (16.2% [95% CI, 13.0%-19.8%]). Study-defined unnecessary angiography occurred in 69 (28.8%) in the NICE guidelines group, 36 (7.5%) in the CMR group, and 34 (7.1%) in the MPS group; adjusted odds ratio of unnecessary angiography: CMR group vs NICE guidelines group, 0.21 (95% CI, 0.12-0.34, P < .001); CMR group vs the MPS group, 1.27 (95% CI, 0.79-2.03, P = .32). Positive angiography proportions were 12.1% (95% CI, 8.2%-16.9%; 29/240 patients) for the NICE guidelines group, 9.8% (95% CI, 7.3%-12.8%; 47/481 patients) for the CMR group, and 8.7% (95% CI, 6.4%-11.6%; 42/481 patients) for the MPS group. A MACE was reported at a minimum of 12 months in 1.7% of patients in the NICE guidelines group, 2.5% in the CMR group, and 2.5% in the MPS group (adjusted hazard ratios: CMR group vs NICE guidelines group, 1.37 [95% CI, 0.52-3.57]; CMR group vs MPS group, 0.95 [95% CI, 0.46-1.95]). CONCLUSIONS AND RELEVANCE: In patients with suspected angina, investigation by CMR resulted in a lower probability of unnecessary angiography within 12 months than NICE guideline-directed care, with no statistically significant difference between CMR and MPS strategies. There were no statistically significant differences in MACE rates. TRIAL REGISTRATION: Clinicaltrials.gov Identifier: NCT01664858.

Current Concepts in the Pathogenesis of Takotsubo Syndrome.

Takotsubo syndrome is typically characterized by acute reversible impairment of apical and mid -left ventricular systolic function. The pathophysiology is complex and remains to be completely understood. A catecholamine surge appears to be a central feature. Patients with prior history of psychiatric disorders have a predisposition. The putative role of a switch in b-adrenoceptor signalling resulting in negative inotropy remains uncertain. Downregulation of noncritical cellular functions may offer some protection in preventing irreversible cellular necrosis. Microvascular function is a common occurrence in these patients.

Coronary endothelial dysfunction is associated with inflammation and vasa vasorum proliferation in patients with early atherosclerosis.

OBJECTIVE: Endothelial dysfunction is an early manifestation of atherosclerosis. Inflammation and vasa vasorum play a pivotal role in the pathophysiology of plaque initiation, development, and complications. Optical coherence tomography allows high-resolution imaging of tissue microstructure. Therefore, the aim of this study was to test the hypothesis that segments with endothelial dysfunction show macrophages and vasa vasorum in patients with early coronary artery disease. APPROACH AND RESULTS: Optical coherence tomography images were obtained from 40 patients with mild coronary atherosclerosis who underwent coronary endothelial function assessment. Optical coherence tomography findings, including macrophages and microchannels, were evaluated in 76 coronary segments corresponding to those in endothelial response to acetylcholine. Coronary artery diameter change in response to acetylcholine was more severe in segments showing macrophages (-17.7±14.7% versus -6.3±13.9%; P<0.01) and microchannels (-15.9±15.9% versus -6.4±13.5%; P<0.01) than those without. There were increasing trends of the prevalence of macrophages and microchannels with endothelial dysfunction as stratified by quartiles of coronary artery diameter change (P<0.01 and P=0.02 for trend, respectively). In particular, segments with both macrophages and microchannels (n=12) tended to have worse endothelial function than those with macrophages alone (n=15) and microchannels alone (n=15; -22.1±14.6% versus -10.9±15.6% and -10.9±15.6%; P=0.07 and P=0.06, respectively). CONCLUSIONS: Epicardial endothelial dysfunction was associated with optical coherence tomography -identified macrophages and microchannels in mild coronary atherosclerosis. The current study further supports the role of inflammation and vasa vasorum proliferation in the early stage of coronary atherosclerosis.

Spatial heterogeneity of neoatherosclerosis and its relationship with neovascularization and adjacent plaque characteristics: optical coherence tomography study.

BACKGROUND: Development of neoatherosclerosis (NA) has been reported to be a potential cause of late stent failure. However, the distribution of NA and its relationship with neovascularization (NV) and adjacent plaque characteristics remain unclear. METHODS: We investigated 167 stents (40 bare-metal stents, 84 sirolimus-eluting stents, and 43 everolimus-eluting stents) with optical coherence tomography. Each stent was divided into the proximal section (PS), mid section (MS) and distal section (DS). Neoatherosclerosis was defined as lipid-laden neointima or calcification inside stent. Adjacent plaque characteristics were evaluated within 5 mm proximal and distal reference segments. RESULTS: Neoatherosclerosis was more frequent in PS and DS than in MS (PS 19.8% vs. MS 3.6% vs. DS 21%: PS vs. MS, P < .001: MS vs. DS, P < .001). Neovascularization in PS and DS was also more prevalent compared with that in MS (PS 15% vs. MS 5.4% vs. DS 13.8%: PS vs. MS, P = .001: MS vs. DS, P = .001). Neoatherosclerosis was more frequently observed in stents with intraintima NV (68.6% vs. 20.5%, P < .001). The incidence of NA was higher, when adjacent plaque was lipid (43.2% with lipid plaque vs. 12.2% without lipid plaque, P < .001). CONCLUSION: Neoatherosclerosis occurs more frequently at PS and DS. Neoatherosclerosis was associated with NV and adjacent lipid plaque, suggesting potential interrelationship between development of NA and NV and adjacent plaque characteristics.

Pancoronary plaque vulnerability in patients with acute coronary syndrome and ruptured culprit plaque: a 3-vessel optical coherence tomography study.

BACKGROUND: Recent studies described different clinical and underlying plaque characteristics between patients with and without plaque rupture presenting with acute coronary syndrome (ACS). In light of the systemic nature of atherosclerosis, we hypothesized that nonculprit plaques might also express different morphological features in these 2 groups of patients. METHODS: Thirty-eight patients with ACS who underwent 3-vessel optical coherence tomography imaging were identified from the Massachusetts General Hospital Optical Coherence Tomography Registry. Based on culprit plaque morphology, the study population was divided into 2 groups: patients with plaque rupture at the culprit lesion (group 1) and patients with nonruptured plaque at the culprit lesion (group 2). Prevalence and features of nonculprit plaques were compared between the 2 groups. RESULTS: A total of 118 nonculprit plaques were analyzed. Patients in group 1 (n = 17) had nonculprit plaques with higher prevalence of thin-cap fibroatheroma (52.9% vs 19.0%, P = .029) and disruption (35.3% vs 4.8%, P = .016) compared with patients in group 2 (n = 21). Nonculprit plaques in group 1 showed wider maximum lipid arc (198.9° ± 41.7° vs 170.2° ± 41.9°, P = .003), greater lipid length (7.8 ± 4.4 mm vs 5.1 ± 2.4 mm, P = .003), higher lipid index (1196.9 ± 700.5 vs 747.7 ± 377.3, P = .001), and thinner fibrous cap (107.0 ± 56.5 µm vs 137.3 ± 69.8 µm, P = .035) compared with those in group 2. CONCLUSIONS: The present study showed distinctive features of nonculprit plaques between patients with ACS caused by plaque rupture and patients with ACS caused by nonruptured plaques. Patients with plaque rupture had increased pancoronary vulnerability in nonculprit plaques, suggesting that a more aggressive treatment paradigm aiming at the stabilization of vulnerable plaques may offer additional benefit to these patients.

Incidence and angiographic characteristics of patients with apical ballooning syndrome (takotsubo/stress cardiomyopathy) in the HORIZONS-AMI trial: an analysis from a multicenter, international study of ST-elevation myocardial infarction.

OBJECTIVES: To determine the incidence, clinical characteristics, and the coronary angiographic features of patients with apical ballooning syndrome (ABS) among those recruited into a large, prospective, international, multicenter trial. BACKGROUND: ABS is an important entity in the differential diagnosis of ST-elevation myocardial infarction (STEMI). Current data regarding ABS are limited to single center registries. METHODS: Patients with ABS were identified, based on the Mayo Clinic diagnostic criteria, from those enrolled into the HORIZONS-AMI trial. Quantitative angiography was performed by a core laboratory to identify the frequency and severity of coronary artery disease. RESULTS: Among the 2,648 patients who had left ventriculography in addition to coronary angiography, 12 patients were identified with ABS. All patients were female and they were compared to the remaining 571 female patients with STEMI. Compared with patients with STEMI (97.9% of our cohort), patients with ABS (2.1%) had a lower prevalence (42% vs. 100%, P < 0.05) and severity (number of plaques measuring >30% diameter stenosis per patient: 0.58 ± 0.90 vs. 4.13 ± 2.68, P < 0.0001) of coronary artery disease. There were no in-hospital deaths or major adverse cardiovascular events (MACE) in the ABS group vs. 2.1% and 3.7% respectively in the STEMI group, nor at 2-year follow up (death: 0% vs. 5.5%, MACE: 0% vs. 19.4%), but these differences were not statistically significant. CONCLUSIONS: In HORIZONS-AMI, ABS was identified exclusively in women (2.1% of female patients, 0.5% of all patients) and MACE were absent in this uncommon but important group of patients. Coronary artery disease was often present in patients with ABS, but its prevalence and severity was significantly less compared with STEMI patients.

Outcomes in patients with sustained ventricular tachyarrhythmias occurring within 48 h of acute myocardial infarction: when is ICD appropriate?

AIMS: Recent guidelines for implantable cardioverter-defibrillator (ICD) use in patients with early ventricular arrhythmia (VA) after acute myocardial infarction (MI) are based on systolic function and revascularization status, yet decision to implant an ICD remains highly subjective. We aimed to determine characteristics, utilization of ICDs, and long-term outcomes of survivors of early VA (<48 h) after acute MI. METHODS AND RESULTS: We retrospectively analyzed clinical characteristics, ICD therapies, and survival in 128 patients with early VA after acute MI from 2002-12. Patients were classified for appropriateness of ICD implantation, per 2013 Appropriate Use Criteria (AUC). In 128 early VA survivors after MI, older age, female gender, history of coronary artery bypass graft surgery (CABG) or MI, non-ST-elevation MI or ventricular tachycardia (VT) at presentation predicted worse overall survival (all P < 0.05). While left ventricular ejection fraction (LVEF) did not predict mortality (HR = 1; P = 0.86), post-MI ventricular fibrillation (VF) portended a better long-term prognosis than VT (HR = 0.37; P = 0.001). Twenty-six (20%) early VA survivors received ICD, corresponding well with AUC. Implantable cardioverter-defibrillator recipients had lower post-MI LVEF (P = 0.02) and more frequently presented with non-ST-elevation MI (P = 0.007). Over 2.4 years of median follow-up, ICD recipients had a greater mortality rate than non-ICD recipients (42 vs. 17%; P = 0.02). Appropriate and inappropriate ICD discharges were high in ICD recipients. CONCLUSION: Early VA survivors after MI receiving ICD due to suspected non-reversible arrhythmogenic substrate have high rates of appropriate ICD therapy and mortality. Our ICD implantation practice corresponds well with the AUC. Sustained monomorphic VT and non-ST-elevation MI at presentation predict increased risk for death. Larger prospective studies are necessary to confirm our findings, such as to provide evidence for future ICD guidelines.

Diagnosis of Takotsubo cardiomyopathy.

Takotsubo cardiomyopathy, also known as left ventricular apical ballooning syndrome and stress-induced cardiomyopathy, is typically characterized by transient systolic dysfunction of the apical and mid-segments of the left ventricle, in the absence of obstructive coronary artery lesions. Patients may present with symptoms and signs of acute coronary syndrome, and the provider is challenged to differentiate between these conditions. In this review, we guide the reader through the diagnostic pathway, focusing on differential diagnoses and diagnostic criteria for takotsubo cardiomyopathy.

Fractional flow reserve with dobutamine challenge and coronary microvascular endothelial dysfunction in symptomatic myocardial bridging.

BACKGROUND: Myocardial bridging (MB) results in compression of the coronary artery lumen in systole, extending into diastole with resultant hemodynamic alternation as reflected by fractional flow reserve (FFR). MB has also been associated with coronary endothelial dysfunction. The objective of this study was to investigate relationship between FFR with dobutamine challenge and coronary microvascular endothelial dysfunction in symptomatic MB. METHODS AND RESULTS: Seventeen consecutive patients who had cardiac catheterization assessment of MB were enrolled. The patients were divided into 2 groups according to normal (% increase in coronary blood flow [%CBF] ≥50%, n=7) or impaired (%CBF <50%, n=10) coronary microvascular endothelial function assessed on vasoreactivity in the coronary artery with intracoronary infusion of acetylcholine (Ach). Myocardial ischemia was then assessed using FFR at rest and during i.v. dobutamine infusion challenge across the MB with intracoronary pressure wires. FFR was significantly decreased at peak dobutamine infusion compared to at rest in the impaired group (0.85±0.06 vs. 0.91±0.05, P=0.001), but not in the normal group (0.93±0.05 vs. 0.91±0.07, P=0.618). Both FFR at rest and at peak dobutamine infusion had a positive correlation with %CBF by Ach in the impaired group (r(2)=0.46, P=0.030; r(2)=0.52, P=0.018, respectively). CONCLUSIONS: Microvascular endothelial dysfunction was associated with decreased FFR at peak dobutamine stress in patients with symptomatic MB.

Coronary endothelial dysfunction in patients with early coronary artery disease is associated with the increase in intravascular lipid core plaque.

AIMS: Endothelial dysfunction is considered to play a key role in the development of atherosclerosis. However, only a limited number of human imaging studies have been available to demonstrate this hypothesis. The present study used near-infrared spectroscopy (NIRS) to investigate whether coronary endothelial dysfunction is associated with the lipid core plaque (LCP) in patients with early coronary artery disease. METHODS AND RESULTS: A total of 32 patients with chest pain who had diameter stenosis <30% were enrolled. All patients underwent coronary endothelial function assessment using intracoronary acetylcholine infusion and NIRS of the proximal left anterior descending artery. The lipid core burden index (LCBI), LCBI/L (LCBI divided by the length of scanned artery), maxLCBI4mm (maximum value of LCBI for any of the 4-mm segment) and block chemogram (yellow: probability of LCP presence >0.98, tan: 0.84 ≤ P ≤ 0.98, orange: 0.57 ≤ P ≤ 0.84, red: P < 0.57) were measured. The mean percentage of yellow, tan, and orange colour blocks in patients with epicardial endothelial dysfunction was significantly higher than in those with normal epicardial endothelial function (9.5 ± 11.4 vs. 3.1 ± 6.5%, P = 0.042). There was a significant correlation between LCBI (r = -0.460, P = 0.008), LCBI/L (r = -0.453, P = 0.009), and maxLCBI4mm (r = -0.431, P = 0.014) and the degree of epicardial endothelial function. However, there was no significant correlation between LCBI (r = -0.101, P = 0.58), LCBI/L (r = -0.099, P = 0.59), and maxLCBI4mm (r = -0.063, P = 0.73) and the degree of microvascular endothelial function. CONCLUSION: Patients with early coronary artery disease and endothelial dysfunction had a higher lipid content in the vascular wall than patients with normal endothelial function. The result of the present study supports the hypothesis that endothelial dysfunction is associated with pathogenesis of early atherosclerosis.

Acute coronary occlusion and percutaneous coronary intervention after out-of-hospital cardiac arrest.

OBJECTIVES: Early coronary angiography (CAG) has been recommended in selected patients following out-of-hospital-cardiac-arrest (OHCA). We aimed to identify clinical features associated with acute coronary occlusion (ACO) and evaluate the associations between ACO, successful percutaneous coronary intervention (PCI) and outcomes in this population. METHODS: We included comatose OHCA patients treated with targeted temperature management (TTM) between December 2005 and September 2016 who underwent early CAG within 24 hours. The co-primary outcomes were all-cause 30-day mortality and good neurological outcome (modified Rankin Score [mRS] ≤2) at hospital discharge. RESULTS: Among 155 patients (93% shockable arrest rhythm, 55% with ST elevation), 133 (86%) had coronary artery stenosis ≥50% and 65 (42%) had ACO. ST elevation (sensitivity 74%, specificity 59%, OR 4.0, 95% CI 2.0-8.1) and elevated first troponin (sensitivity 88%, specificity 26%, OR 2.5, 95% CI 1.1-6.1) had limited sensitivity and specificity for ACO. Unadjusted 30-day mortality did not differ significantly by coronary disease severity or ACO. Successful PCI was associated with a lower risk of 30-day mortality (adjusted HR 0.5, 95% CI 0.2-0.9, P=.03), especially among patients with ACO (adjusted HR 0.4, 95% CI 0.1-0.9, P=0.03). After adjustment, ACO and PCI were not associated with the probability of good neurological outcome. CONCLUSIONS: In this select cohort of resuscitated OHCA patients undergoing CAG, unstable coronary disease is highly prevalent and successful PCI was associated with a higher probability of 30-day survival, especially among those with ACO. Neither ACO nor successful PCI were independently associated with good neurological outcome.

Patients With Coronary Microvascular Dysfunction Have Less Circulating α-Klotho.

BACKGROUND: Coronary microvascular dysfunction (CMD) represents an early functional characteristic of coronary vascular aging. Klotho (α-klotho) is a circulating protein inversely linked to physiological aging. We examined low klotho as a potential marker for vascular aging in patients with CMD and no coronary artery disease. METHODS AND RESULTS: Patients undergoing nonurgent angiogram for chest pain who had no coronary artery disease underwent invasive coronary microvascular and endothelial function testing. CMD was defined by ≤50% increase in coronary blood flow (percentage change in coronary blood flow) in response to intracoronary acetylcholine or coronary flow reserve ≤2. Fresh arterial whole blood was used to analyze circulating endothelial progenitor cells with flow cytometry. Stored arterial plasma was used for klotho analysis by ELISA. Participants with CMD (n=62) were compared with those without CMD (n=36). Those with CMD were age 55±10 years (versus 51±11 years; P=0.07) and 73% women (versus 81%; P=0.38). Traditional risk factors for coronary artery disease were similar between groups. Patients with CMD had less klotho (0.88±1.50 versus 1.75±2.38 ng/mL; P=0.03), and the odds of low klotho in CMD were significant in a logistic regression model after adjusting for traditional cardiovascular risk factors (odds ratio [OR], 0.80 [95% CI, 0.636-0.996]; P=0.05). Higher klotho was associated with higher numbers of endothelial progenitor cells with vascular regenerative potential (CD34+ and CD34+CD133+KDR+). Among a subgroup of patients with atherosclerotic cardiovascular disease risk <5% (n=58), CMD remained associated with lower klotho (OR, 0.80 [95% CI, 0.636-0.996]; P=0.047). CONCLUSIONS: Klotho may be a biomarker for CMD and may be a therapeutic target for groups of patients without significant traditional cardiovascular risk.