Changes in Coronary Plaque Composition in Patients With Acute Myocardial Infarction Treated With High-Intensity Statin Therapy (IBIS-4): A Serial Optical Coherence Tomography Study.

OBJECTIVES: This study assessed changes in optical coherence tomography (OCT)-defined plaque composition in patients with ST-elevation myocardial infarction (STEMI) receiving high-intensity statin treatment. BACKGROUND: OCT is a high-resolution modality capable of measuring plaque characteristics including fibrous cap thickness (FCT) and macrophage infiltration. There is limited in vivo evidence regarding the effects of statins on OCT-defined coronary atheroma composition and no evidence in the context of STEMI. METHODS: In the IBIS-4 (Integrated Biomarker Imaging Study-4), 103 patients underwent intravascular ultrasonography and OCT of 2 noninfarct-related coronary arteries in the acute phase of STEMI. Patients were treated with high-dose rosuvastatin for 13 months. Serial OCT imaging was available in 153 arteries from 83 patients. We measured FCT by using a semi-automated method. Co-primary endpoints consisted of the change in minimum FCT (measured in fibroatheromas) and change in macrophage line arc. RESULTS: At 13 months, median low-density lipoprotein cholesterol had decreased from 128 mg/dl to 73.6 mg/dl. Minimum FCT, measured in 31 lesions from 27 patients, increased from 64.9 ± 19.9 µm to 87.9 ± 38.1 µm (p = 0.008). Macrophage line arc decreased from 9.6° ± 12.8° to 6.4° ± 9.6° (p < 0.0001). The secondary endpoint, mean lipid arc, decreased from 55.9° ± 37° to 43.5° ± 33.5°. In lesion-level analyses (n = 191), 9 of 13 thin-cap fibroatheromata (TCFAs) at baseline (69.2%) regressed to non-TCFA morphology, whereas 2 of 178 non-TCFA lesions (1.1%) progressed to TCFAs. CONCLUSIONS: In this observational study, we found significant increase in minimum FCT, reduction in macrophage accumulation, and frequent regression of TCFAs to other plaque phenotypes in nonculprit lesions of patients with STEMI treated with high-intensity statin therapy.

Frequency, Reasons, and Impact of Premature Ticagrelor Discontinuation in Patients Undergoing Coronary Revascularization in Routine Clinical Practice: Results From the Bern Percutaneous Coronary Intervention Registry.

BACKGROUND: Although ticagrelor has improved clinical outcomes among patients with acute coronary syndrome compared with clopidogrel, adherence to this new antiplatelet agent in real-world practice has not been fully investigated. METHODS AND RESULTS: Between November 2011 and June 2014, 1278 of 4831 consecutive patients (26.5%) undergoing percutaneous coronary intervention at a tertiary care center were treated with ticagrelor. Premature ticagrelor cessation was categorized into (1) change, when ticagrelor was replaced by prasugrel; (2) de-escalation, when ticagrelor was replaced by clopidogrel; and (3) premature discontinuation, when ticagrelor was discontinued without P2Y12 inhibitor replacement. Of 1278 patients treated with ticagrelor, premature treatment cessation occurred in 212 patients (17%). De-escalation to clopidogrel was the most frequent scenario (57%; n=120), followed by premature discontinuation (28%; n=60) and change to prasugrel (15%; n=32). Reasons for ticagrelor cessation included adverse effects (49%), initiation of oral anticoagulation (19%), and unspecified general practitioner preference (10%). Most frequent adverse effects leading to premature ticagrelor cessation were bleeding (41%), dyspnea (29%), and gastrointestinal symptoms (18%). Premature ticagrelor cessation was not associated with an increased risk of cardiac death, myocardial infarction, or stroke (hazard ratio, 0.73; 95% confidence interval: 0.40-1.32; P=0.29). CONCLUSIONS: Premature ticagrelor cessation in routine clinical practice occurred in 1 of 6 patients and was primarily related to adverse effects among which bleeding and dyspnea were the most frequent. Although premature ticagrelor cessation was not associated with adverse cardiovascular outcomes, this finding requires careful interpretation in view of the modest sample size. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov. Unique identifier: NCT02241291.

Impact of Patient and Lesion Complexity on Long-Term Outcomes Following Coronary Revascularization With New-Generation Drug-Eluting Stents.

Long-term clinical outcomes of new-generation drug-eluting stents in complex anatomic and clinical settings are not well defined. This study assessed the impact of patient and lesion complexity on 2-year outcomes after coronary revascularization with ultrathin strut biodegradable-polymer (BP) sirolimus-eluting stents (SES) versus durable-polymer (DP) everolimus-eluting stents (EES). In a prespecified analysis of the BIOSCIENCE randomized trial (NCT01443104), complex patients (911 of 2,119; 43%) were defined by the presence of acute ST-elevation myocardial infarction (MI); left ventricular ejection fraction ≤30%; renal dysfunction; insulin-treated diabetes; treatment of ostial lesion, bypass graft, unprotected left main lesion; or 3-vessel intervention. The primary end point was target lesion failure (TLF), a composite of cardiac death, target vessel MI, and clinically indicated target lesion revascularization. At 2 years, complex compared with simple patients had a greater risk of TLF (14.5% vs 7.4%, risk ratio 2.05, 95% confidence interval 1.56 to 2.69; p <0.001). The difference was sustained beyond 1 year on landmark analysis. Complex patients had higher rates of the patient-oriented composite end point of death, any MI, or any revascularization (23% vs 14.4%; p <0.001) as well as definite stent thrombosis (1.6% vs 0.4%, p = 0.006). There were no differences in TLF and patient-oriented composite end point between the BP-SES versus DP-EES, consistently among simple and complex patients. In conclusion, patient and lesion complexity had a durable adverse impact on clinical outcomes throughout 2 years of follow-up in this all-comers randomized trial. Safety and efficacy of new-generation BP-SES and DP-EES were comparable, irrespective of complexity status.

Predictors of Early (1-Week) Outcomes Following Left Atrial Appendage Closure With Amplatzer Devices.

OBJECTIVES: The aim of this study was to assess predictors of adverse 1-week outcomes and determine the effect of left atrial appendage (LAA) morphology following LAA closure (LAAC) with Amplatzer devices. BACKGROUND: Percutaneous LAAC is a valuable treatment option for stroke prevention in patients with atrial fibrillation. Determinants of procedural safety events with Amplatzer occluders are not well established, and the possibly interrelating effect of LAA anatomy is unknown. METHODS: Between 2009 and 2014, 500 consecutive patients with atrial fibrillation ineligible or at high risk for oral anticoagulation underwent LAAC using Amplatzer devices. Procedure- and device-related major adverse events (MAEs) were defined as the composite of death, stroke, major or life-threatening bleeding, serious pericardial effusion, device embolization, major access-site vascular complication, or need for cardiovascular surgery within 7 days following the intervention. RESULTS: Patients (mean age 73.9 ± 10.1 years) were treated with Amplatzer Cardiac Plug (n = 408 [82%]) or Amulet (n = 92 [18%]) devices. Early procedural success was 97.8%, and MAEs occurred in 29 patients (5.8%). Independent predictors of MAEs included device repositioning (odds ratio: 9.13; 95% confidence interval: 2.85 to 33.54; p < 0.001) and left ventricular ejection fraction <30% (odds ratio: 4.08; 95% confidence interval: 1.49 to 11.20; p = 0.006), with no effect of device type or size. Angiographic LAA morphology, characterized as cauliflower (33%), cactus (32%), windsock (20%), or chicken wing (15%), was not associated with procedural success (p = 0.51) or the occurrence of MAEs (p = 0.78). CONCLUSIONS: In this nonrandomized study, procedural success of LAAC using Amplatzer devices was high. MAEs within 7 days were predicted by patient- and procedure-related factors. Although LAA morphology displayed substantial heterogeneity, outcomes were comparable across the spectrum of LAA anatomies.

Impact of Diabetic Status on Outcomes After Revascularization With Drug-Eluting Stents in Relation to Coronary Artery Disease Complexity: Patient-Level Pooled Analysis of 6081 Patients.

BACKGROUND: Diabetes mellitus and angiographic coronary artery disease complexity are intertwined and unfavorably affect prognosis after percutaneous coronary interventions, but their relative impact on long-term outcomes after percutaneous coronary intervention with drug-eluting stents remains controversial. This study determined drug-eluting stents outcomes in relation to diabetic status and coronary artery disease complexity as assessed by the Synergy Between PCI With Taxus and Cardiac Surgery (SYNTAX) score. METHODS AND RESULTS: In a patient-level pooled analysis from 4 all-comers trials, 6081 patients were stratified according to diabetic status and according to the median SYNTAX score ≤11 or >11. The primary end point was major adverse cardiac events, a composite of cardiac death, myocardial infarction, and clinically indicated target lesion revascularization within 2 years. Diabetes mellitus was present in 1310 patients (22%), and new-generation drug-eluting stents were used in 4554 patients (75%). Major adverse cardiac events occurred in 173 diabetics (14.5%) and 436 nondiabetic patients (9.9%; P<0.001). In adjusted Cox regression analyses, SYNTAX score and diabetes mellitus were both associated with the primary end point (P<0.001 and P=0.028, respectively; P for interaction, 0.07). In multivariable analyses, diabetic versus nondiabetic patients had higher risks of major adverse cardiac events (hazard ratio, 1.25; 95% confidence interval, 1.03-1.53; P=0.026) and target lesion revascularization (hazard ratio, 1.54; 95% confidence interval, 1.18-2.01; P=0.002) but similar risks of cardiac death (hazard ratio, 1.41; 95% confidence interval, 0.96-2.07; P=0.08) and myocardial infarction (hazard ratio, 0.89; 95% confidence interval, 0.64-1.22; P=0.45), without significant interaction with SYNTAX score ≤11 or >11 for any of the end points. CONCLUSIONS: In this population treated with predominantly new-generation drug-eluting stents, diabetic patients were at increased risk for repeat target-lesion revascularization consistently across the spectrum of disease complexity. The SYNTAX score was an independent predictor of 2-year outcomes but did not modify the respective effect of diabetes mellitus. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifiers: NCT00297661, NCT00389220, NCT00617084, and NCT01443104.

Clinical impact of gastrointestinal bleeding in patients undergoing percutaneous coronary interventions.

BACKGROUND: The risk factors and clinical sequelae of gastrointestinal bleeding (GIB) in the current era of drug-eluting stents, prolonged dual antiplatelet therapy, and potent P2Y12 inhibitors are not well established. We determined the frequency, predictors, and clinical impact of GIB after percutaneous coronary interventions (PCIs) in a contemporary cohort of consecutive patients treated with unrestricted use of drug-eluting stents. METHODS AND RESULTS: Between 2009 and 2012, all consecutive patients undergoing PCI were prospectively included in the Bern PCI Registry. Bleeding Academic Research Consortium (BARC) GIB and cardiovascular outcomes were recorded within 1 year of follow-up. Among 6212 patients, 84.1% received new-generation drug-eluting stents and 19.5% received prasugrel. At 1 year, GIB had occurred in 65 patients (1.04%); 70.8% of all events and 84.4% of BARC ≥ 3B events were recorded > 30 days after PCI. The majority of events (64.4%) were related to upper GIB with a more delayed time course compared with lower GIB. Increasing age, previous GIB, history of malignancy, smoking, and triple antithrombotic therapy (ie, oral anticoagulation plus dual antiplatelet therapy) were independent predictors of GIB in multivariable analysis. GIB was associated with increased all-cause mortality (adjusted hazard ratio, 3.40; 95% confidence interval, 1.67-6.92; P = 0.001) and the composite of death, myocardial infarction, or stroke (adjusted hazard ratio, 3.75; 95% confidence interval, 1.99-7.07; P < 0.001) and was an independent predictor of all-cause mortality during 1 year. CONCLUSIONS: Among unselected patients undergoing PCI, GIB has a profound effect on prognosis. Triple antithrombotic therapy emerged as the single drug-related predictor of GIB in addition to patient-related risk factors within 1 year of PCI. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT02241291.

Sinus nodal response to adenosine relates to the severity of sinus node dysfunction.

AIMS: It is unknown as to whether the result of adenosine testing for the diagnosis of sinus node dysfunction (SND) depends on the clinical presentation. We investigated whether syncope or presyncope are associated with a more pronounced sinus nodal inhibition by adenosine in SND. METHODS AND RESULTS: We studied 46 patients with SND, 33 with syncope or presyncope and 13 without such history. Controls were 30 subjects undergoing electrophysiological studies for supraventricular tachycardia or unexplained syncope. We calculated the corrected sinus node recovery time after intravenous adenosine 0.15 mg/kg (ADSNRT) as well as after atrial pacing (CSNRT). Corrected sinus node recovery time values >525 ms were considered abnormal. Corrected sinus node recovery time after adenosine injection was more prolonged in SND patients with syncope or presyncope as compared with those without such history [median: 4900 inter-quartile range (IQR): 920-8560 ms vs. median: 280 IQR: 5-908 ms; P< 0.005]. In SND patients with syncope or presyncope ADSNRT was more prolonged than CSNRT (median: 4900 IQR: 920-8560 ms vs. median: 680 IQR: 359-1650 ms, P< 0.01). In SND patients without syncope or presyncope no statistical difference was noted between ADSNRT and CSNRT (median: 280 IQR: 5-908 ms vs. median: 396 IQR: 270-600 ms, P = 0.80). The sensitivity of CSNRT for SND diagnosis was 57% and the specificity was 100%. A cut-off of 1029 ms for ADSRNT yields the same sensitivity with a specificity of 96.6%. CONCLUSION: In patients with SND syncope or presyncope relate to an exaggerated sinus nodal suppression by adenosine. Prolonged ADSNRT can diagnose cases with severe underlying SND where a more aggressive management strategy is probably warranted.

Selective inhibition of matrix metalloproteinase-13 increases collagen content of established mouse atherosclerosis.

OBJECTIVE: Evidence has linked collagen loss with the onset of acute coronary events. This study tested the hypothesis that selective matrix metalloproteinase-13 (MMP-13) collagenase inhibition increases collagen content in already established and nascent mouse atheromas. METHODS AND RESULTS: In vitro and in situ experiments documented the selectivity and efficacy of an orally available MMP-13 inhibitor (MMP13i-A). In vivo observations monitored macrophage accumulation and MMP-13 activity using molecular imaging. After 10 weeks of MMP13i-A treatment, apolipoprotein E-deficient mice with evolving or established lesions exhibited reduced MMP-13 activity without affecting macrophage content, measured either by intravital microscopy or fluorescence reflectance imaging. Histological analysis indicated that MMP13-iA did not affect plaque size or macrophage or smooth muscle cell accumulation. Administration of MMP13i-A to mice with evolving or established atheromas substantially increased plaque interstitial collagen content in the intima and locally in the fibrous cap, compared with vehicle-treated controls. Analysis of collagen revealed thicker collagen fibers within the plaques of treated groups. CONCLUSION: Pharmacological MMP-13 inhibition yields collagen accumulation in plaques (a feature associated in humans with resistance to rupture), even in established plaques. This study, of considerable clinical relevance, furnishes new mechanistic insight into regulation of the plaque's extracellular matrix and validates molecular imaging for studying plaque biology.

Extremely rare case of primary cardiac chondroma in a patient presenting with acute pulmonary edema.

Primary tumors of the heart are rare entities, substantially less frequent than cardiac metastases. Primary chondroma is an exceptionally rare cardiac tumor. We describe the case of a patient presenting with acute pulmonary edema with the incidental echocardiographic finding of a large left atrial tumor that was histopathologically diagnosed as primary cardiac chondroma.

Echocardiographic manifestation of hiatus hernia simulating a left atrial mass: case report.

BACKGROUND: Despite the high prevalence of hiatus hernia, a relatively small number of echocardiographically manifested cases have been reported. CASE PRESENTATION: An 82-year old woman presented with acute retrosternal pain indicative of cardiac etiology. Physical examination and biochemical tests, as well as 12-lead electrocardiogram, were normal. A two-dimensional transthoracic echocardiogram was performed and revealed a structure that was considered to represent a left atrial mass. A subsequent computed tomography scan visualized a hiatus hernia in the posterior mediastinum, impinging on the posterior left atrial wall. The intrathoracic displacement of a large part of the stomach was further confirmed by an upper gastrointestinal barium examination. CONCLUSION: Hiatus hernia can present as acute chest pain, while its echocardiographic manifestation may resemble a left atrial space-occupying structure. Physicians should be aware of the clinical and sonographic findings to facilitate the differential diagnosis from similarly presenting cardiac entities.