Roy Beinart

Clopidogrel Resistance Is Associated With Increased Risk of Recurrent Atherothrombotic Events in Patients With Acute Myocardial Infarction

Background— Although clopidogrel reduces the risk of cardiovascular episodes after coronary events and stenting, a substantial number of incidents continue to occur. Methods and Results— The antiplatelet effect of clopidogrel was studied prospectively in 60 consecutive patients who underwent primary angioplasty (percutaneous coronary intervention [PCI]) with stenting for acute ST-segment–elevation myocardial infarction (STEMI) to determine whether variability in response to clopidogrel affects clinical outcomes. Patients were stratified into 4 quartiles according to the percentage reduction of ADP-induced platelet aggregation. Although patients in the first quartile were resistant to the effects of clopidogrel (ADP-induced platelet aggregation at day 6, 103±8% of baseline), ADP-induced aggregation was reduced to 69±3%, 58±7%, and 33±12% of baseline, respectively, in patients in quartiles 2 through 4 (P <0.01 for all). In addition, epinephrine-induced platelet aggregation and platelet aggregation under flow conditions, assessed by the cone-and-plate(let) analyzer method, were reduced significantly less in the first quartile than in quartiles 2 through 4. Whereas 40% of patients in the first quartile sustained a recurrent cardiovascular event during a 6-month follow-up, only 1 patient (6.7%) in the second quartile and none in the third and fourth quartiles suffered a cardiovascular event (P =0.007). Conclusions— Up to 25% of STEMI patients undergoing primary PCI with stenting are resistant to clopidogrel and therefore may be at increased risk for recurrent cardiovascular events.

Relationship between left atrial appendage morphology and stroke in patients with atrial fibrillation

BACKGROUNDnAtrial fibrillation (AF) is an important cause of stroke. Given the morbidity and mortality associated with stroke, the risk stratification of patients based on left atrial appendage (LAA) characteristics is of great interest.nnnOBJECTIVEnTo explore the association between LAA morphology and LAA characteristics including the extent of trabeculations, orifice diameter, and length with prevalent stroke in a large cohort of patients with drug refractory AF who underwent AF ablation to develop mechanistic insight regarding the risk of stroke.nnnMETHODSnAn institutional cohort of 1063 patients referred for AF ablation from 2003 to 2012 was reviewed to identify patients that underwent preprocedural cardiac computed tomography (CT). LAA morphology was characterized as chicken wing, cactus, windsock, or cauliflower by using previously reported methodology. Left atrial size and LAA trabeculations, morphology, orifice diameter, and length were compared between patients with prevalent stroke and patients without prevalent stroke.nnnRESULTSnOf 678 patients with CT images, 65 (10%) had prior stroke or transient ischemic attack. In univariate analyses, prevalent heart failure (7.7% in cases vs 2.8% in controls; P = .033), smaller LAA orifice (2.26 ± 0.52 cm vs 2.78 ± 0.71 cm ; P < .001), shorter LAA length (5.06 ± 1.17 cm vs 5.61 ± 1.17 cm; P < .001), and extensive LAA trabeculations (27.7% vs 14.4%; P = .019) were associated with stroke. LAA morphologies were unassociated with stroke risk. In multivariable analysis, smaller LAA orifice diameter and extensive LAA trabeculations remained independently associated with thromboembolic events.nnnCONCLUSIONSnThe extent of LAA trabeculations and smaller LAA orifice diameter are associated with prevalent stroke and may mediate the previously described association of cauliflower LAA morphology with stroke.

Magnetic resonance image intensity ratio, a normalized measure to enable interpatient comparability of left atrial fibrosis.

BACKGROUNDnThe measurement of late gadolinium-enhanced magnetic resonance imaging (LGE-MRI) intensity in arbitrary units limits the objectivity of thresholds for focal scar detection and interpatient comparisons of scar burden.nnnOBJECTIVEnTo develop and validate a normalized measure, the image intensity ratio (IIR), for the assessment of left atrial (LA) scar on LGE-MRI.nnnMETHODSnElectrocardiogram- and respiratory-gated 1.5 Tesla LGE-MRI was performed in 75 patients (75% men; 62 ± 8 years) before atrial fibrillation ablation. The local IIR was defined as LA myocardial signal intensity for each of the 20 sectors on contiguous axial image planes divided by the mean LA blood pool image intensity. Intracardiac point-by-point sampled electroanatomic map points were coregistered with the corresponding image sectors.nnnRESULTSnThe average bipolar voltage for all 8153 electroanatomic map points was 0.9 ± 1.1 mV. In a mixed effects model accounting for within patient clustering, and adjusting for age, LA volume, mass, body mass index, sex, CHA2DS2-VASc score, atrial fibrillation type, history of previous ablations, and contrast delay time, each unit increase in local IIR was associated with 91.3% decrease in bipolar LA voltage (P < .001). Local IIR thresholds of >0.97 and >1.61 corresponded to bipolar voltage <0.5 and <0.1 mV, respectively.nnnCONCLUSIONSnNormalization of LGE-MRI intensity by the mean blood pool intensity results in a metric that is closely associated with intracardiac voltage as a surrogate of atrial fibrosis.

Cardiac magnetic resonance T1 mapping of left atrial myocardium.

BACKGROUNDnCardiac magnetic resonance (CMR) T1 mapping is an emerging tool for objective quantification of myocardial fibrosis.nnnOBJECTIVESnTo (a) establish the feasibility of left atrial (LA) T1 measurements, (b) determine the range of LA T1 values in patients with atrial fibrillation (AF) vs healthy volunteers, and (c) validate T1 mapping vs LA intracardiac electrogram voltage amplitude measures.nnnMETHODSnCMR imaging at 1.5 T was performed in 51 consecutive patients before AF ablation and in 16 healthy volunteers. T1 measurements were obtained from the posterior LA myocardium by using the modified Look-Locker inversion-recovery sequence. Given the established association of reduced electrogram amplitude with fibrosis, intracardiac point-by-point bipolar LA voltage measures were recorded for the validation of T1 measurements.nnnRESULTSnThe median LA T1 relaxation time was shorter in patients with AF (387 [interquartile range 364-428] ms) compared to healthy volunteers (459 [interquartile range 418-532] ms; P < .001) and was shorter in patients with AF with prior ablation compared to patients without prior ablation (P = .035). In a generalized estimating equations model, adjusting for data clusters per participant, age, rhythm during CMR, prior ablation, AF type, hypertension, and diabetes, each 100-ms increase in T1 relaxation time was associated with 0.1 mV increase in intracardiac bipolar LA voltage (P = .025).nnnCONCLUSIONSnMeasurement of the LA myocardium T1 relaxation time is feasible and strongly associated with invasive voltage measures. This methodology may improve the quantification of fibrotic changes in thin-walled myocardial tissues.

Effects of External Electrical and Magnetic Fields on Pacemakers and Defibrillators From Engineering Principles to Clinical Practice

The overall risk of clinically significant adverse events related to EMI in recipients of CIEDs is very low. Therefore, no special precautions are needed when household appliances are used. Environmental and industrial sources of EMI are relatively safe when the exposure time is limited and distance from the CIEDs is maximized. The risk of EMI-induced events is highest within the hospital environment. Physician awareness of the possible interactions and methods to minimize them is warranted.

Acute Myocarditis: Noninvasive Evaluation with Cardiac MRI and Transthoracic Echocardiography

OBJECTIVEnThe diagnosis of acute myocarditis is challenging. Nonspecific clinical presentation and an overlap with the diagnosis of acute myocardial infarction present a diagnostic dilemma. The purpose of this article is to describe the role of cardiac MRI and transthoracic echocardiography (TTE) in the diagnosis of acute myocarditis.nnnMATERIALS AND METHODSnThirty-two sequential patients (all male; average age, 33 years) with clinically suspected myocarditis were included. All patients underwent cardiac MRI with sequences dedicated for the evaluation of myocardial delayed enhancement and TTE for the evaluation of wall motion abnormalities (WMAs). Nine patients were excluded because of diagnosis of acute myocardial infarction (n=2) or inadequate cardiac MRI technique (n=7). Retrospective analysis of the images of the remaining 23 patients was performed.nnnRESULTSnAn epicardial pattern of abnormal patchy myocardial delayed enhancement was seen on cardiac MRI in 21 of 23 (91%) patients. WMAs were seen on TTE in eight of 23 (35%) patients. Regional rather than global involvement was seen mainly in the inferolateral segments, with a predominance in the midventricular portion.nnnCONCLUSIONnCardiac MRI might have a greater impact than TTE in confirming the presence of acute myocarditis and evaluating the extent of myocardial involvement. Cardiac MRI provides noninvasive imaging that may obviate invasive procedures such as coronary catheter angiography or endomyocardial biopsy.

Magnetic Resonance Imaging and Implantable Devices

Magnetic resonance imaging uses high-strength magnetic and electric fields to obtain multiplanar images with unrivaled soft tissue resolution.1,2 The image resolution and availability of various pulse sequences, each optimized for the evaluation of particular tissue attributes, make MRI the imaging modality of choice for numerous neurological, musculoskeletal, thoracic, and abdominal conditions. In addition, because of the absence of x-ray radiation, MRI is optimal for follow-up of chronic diseases that require repeat imaging and for diagnostic imaging in young patients and women of childbearing age. Because of the advancing severity of disease and age of the population, and advances in device technology, the number of patients with permanent pacemakers and implantable cardioverter defibrillators (ICD) continues to increase. It has been estimated that patients with a pacemaker or ICD have up to 75% likelihood of having a clinical indication for MRI over the lifetime of their device. When performed with appropriate supervision and following a protocol for safety, many studies over the past 10 years have reported the safety of MRI with selected devices. However, in older devices, catastrophic complications have also been reported. Familiarity with each device class and its potential for electromagnetic interaction is essential for cardiologists and electrophysiologists whose patients may require MRI.nnMRI uses high-strength magnetic and electric fields to evaluate tissue structure, heterogeneity, and motion. Within the MRI scanner, hydrogen nuclei (predominantly in water and fat) become aligned with or against the axis of the static magnetic field. A net magnetization vector is created because more protons are aligned with the static magnetic field than against it. The protons also rotate around their own axis and precess around the magnetic field lines at a rate dependent on the local magnetic field strength. Weaker gradient magnetic fields are then applied to introduce regional variability in …

Contemporary rates of appropriate shock therapy in patients who receive implantable device therapy in a real-world setting: From the Israeli ICD Registry

BACKGROUNDnImplantable cardioverter-defibrillators (ICDs) have become the mainstay of preventive measures for sudden cardiac death (SCD). However, there are limited data on rates of appropriate life-saving ICD shock therapies in contemporary real-life settings.nnnOBJECTIVEnThe purpose of the study was to evaluate the rate of appropriate life-saving ICD shock therapies in a contemporary registry.nnnMETHODSnThe Israeli ICD Registry includes all implants and other ICD operative procedures nationwide. The present study comprises 2349 consecutive cases who were enrolled in the Registry and prospectively followed up for information regarding survival, hospitalizations, and ICD therapies since 2010.nnnRESULTSnKaplan-Meier survival analysis showed that the rate of appropriate ICD shock therapy at 30-month follow-up was 2.6% among patients who received an ICD for primary prevention compared with 7.4% among those who received a device for secondary prevention (log-rank P < .001). Rates of appropriate ICD shocks among primary prevention patients were 1.1% at 1-year of follow-up and 2.6% at 30 months, whereas the corresponding rates in the secondary prevention group were 3.8% at 1 year and 7.4% at 30 months (log-rank P < .001). A total of 253 patients (4.8%) died during follow-up, 65% of noncardiac causes.nnnCONCLUSIONnRates of life-saving appropriate ICD shock therapies among patients implanted with a defibrillator for the primary prevention of SCD in a contemporary real-world setting are lower than reported previously. These findings suggest a need for improved risk stratification and patient selection in this population.

The QT interval is associated with incident cardiovascular events: the MESA study.

BACKGROUNDnProlonged heart rate-corrected QT interval on electrocardiograms (ECGs) is associated with increasedxa0risk of myocardial infarction and cardiovascular disease (CVD)-related deaths in patients with prevalent coronary heart disease.nnnOBJECTIVESnThis study sought to examine the prognostic association between the baseline QT interval and incident cardiovascular events in individuals without prior known CVD.nnnMETHODSnThe corrected baseline 12-lead ECG QT interval duration (QTcorr) was determined by adjustment for age, sex,xa0race/ethnicity, and RR interval duration in 6,273 participants in MESA (Multi-Ethnic Study of Atherosclerosis). Coxxa0proportional hazards models adjusting for demographic and clinical risk factors were used to examine the association of baseline QTcorr with incident cardiovascular events.nnnRESULTSnThe mean age at enrollment was 61.7 ± 10 years, and 53.4% of participants were women. Cardiovascular events occurred in 291 participants over a mean follow-up of 8.0 ± 1.7 years. Each 10-ms increase in the baseline QTcorr was associated with incident heart failure (hazard ratio [HR]: 1.25; 95% CI: 1.14 to 1.37), CVD events (HR: 1.12; 95% CI: 1.05 to 1.20), and stroke (HR: 1.19; 95% CI: 1.07 to 1.32) after adjustment for CVD risk factors and potential confounders. There was no evidence of interaction with sex or ethnicity.nnnCONCLUSIONSnThe QT interval was associated with incident cardiovascular events in middle-aged and older adults without prior CVD.

The incidence and clinical predictors of early stent thrombosis in patients with acute coronary syndrome.

BACKGROUNDnAcute coronary syndrome (ACS) is associated with activation of platelets and the coagulation system which could influence the incidence of early stent thrombosis (EST). We aimed to determine the incidence and predictors of EST in patients undergoing coronary stenting during ACS.nnnMETHODSnThe study comprised 1202 consecutive patients, drawn from a nationwide ACS survey, who underwent coronary stenting during ACS and were followed up for 30 days. Early stent thrombosis was based on the Academic Research Consortium definition.nnnRESULTSnThirty patients (2.5%) sustained EST. The occurrence of EST in patients with unstable angina/non-ST-elevation myocardial infarction and ST-elevation myocardial infarction (STEMI) was 0.9% and 3.9%, respectively (P < .05), and was even higher (5.2%) in STEMI patients who underwent primary percutaneous coronary intervention. On multivariate analysis, STEMI (OR 6.3, 95% CI 2.1-18, P = .0008), multivessel disease (OR 5.9, 95% CI 1.9-21, P = .003) and Killip class >/=2 (OR 2.9, 95% CI 1.3-6.6, P = .008) were independent correlates of EST. The use of bare versus drug-eluting stents was not associated with any significant difference in EST.nnnCONCLUSIONSnPatients presenting with STEMI who are hemodynamically unstable and have multivessel coronary disease undergoing coronary stenting during ACS, are at increased risk of EST.