Prior Infarction Research Articles

Prior Infarcts, Reactivity, and Angiography in Moyamoya Disease (PIRAMD): a scoring system for moyamoya severity based on multimodal hemodynamic imaging.

OBJECTIVE Quantification of the severity of vasculopathy and its impact on parenchymal hemodynamics is a necessary prerequisite for informing management decisions and evaluating intervention response in patients with moyamoya. The authors performed digital subtraction angiography and noninvasive structural and hemodynamic MRI, and they outline a new classification system for patients with moyamoya that they have named Prior Infarcts, Reactivity, and Angiography in Moyamoya Disease (PIRAMD). METHODS Healthy control volunteers (n = 11; age 46 ± 12 years [mean ± SD]) and patients (n = 25; 42 ± 13.5 years) with angiographically confirmed moyamoya provided informed consent and underwent structural (T1-weighted, T2-weighted, FLAIR, MR angiography) and hemodynamic (T2*- and cerebral blood flow-weighted) 3-T MRI. Cerebrovascular reactivity (CVR) in the internal carotid artery territory was assessed using susceptibility-weighted MRI during a hypercapnic stimulus. Only hemispheres without prior revascularization were assessed. Each hemisphere was considered symptomatic if localizing signs were present on neurological examination and/or there was a history of transient ischemic attack with symptoms referable to that hemisphere. The PIRAMD factor weighting versus symptomatology was optimized using binary logistic regression and receiver operating characteristic curve analysis with bootstrapping. The PIRAMD finding was scored from 0 to 10. For each hemisphere, 1 point was assigned for prior infarct, 3 points for reduced CVR, 3 points for a modified Suzuki Score ≥ Grade II, and 3 points for flow impairment in ≥ 2 of 7 predefined vascular territories. Hemispheres were divided into 3 severity grades based on total PIRAMD score, as follows: Grade 1, 0-5 points; Grade 2, 6-9 points; and Grade 3, 10 points. RESULTS In 28 of 46 (60.9%) hemispheres the findings met clinical symptomatic criteria. With decreased CVR, the odds ratio of having a symptomatic hemisphere was 13 (95% CI 1.1-22.6, p = 0.002). The area under the curve for individual PIRAMD factors was 0.67-0.72, and for the PIRAMD grade it was 0.845. There were 0/8 (0%), 10/18 (55.6%), and 18/20 (90%) symptomatic PIRAMD Grade 1, 2, and 3 hemispheres, respectively. CONCLUSIONS A scoring system for total impairment is proposed that uses noninvasive MRI parameters. This scoring system correlates with symptomatology and may provide a measure of hemodynamic severity in moyamoya, which could be used for guiding management decisions and evaluating intervention response.

Abstract 219: Tumor Necrosis Factor Receptor 1 and Subclinical Cerebrovascular Disease: the Levels of Inflammatory Markers in Treatment of Stroke Study

Background: The role of inflammation in cerebral small vessel disease remains uncertain. Tumor necrosis factor-alpha receptor 1 (TNFR1) has been associated with atherosclerosis and risk of stroke. We hypothesized that TNFR1 concentrations would be associated with cerebral white matter disease (WMD) and subclinical infarcts in patients with recent lacunar stroke. Methods: Levels of Inflammatory Markers in the Treatment of Stroke (LIMITS) was an international, multicenter, ancillary biomarker study nested within the Secondary Prevention of Small Subcortical Strokes trial (SPS3; www.clinicaltrials.gov unique identifier: NCT00059306), a Phase III trial in patients with recent lacunar stroke. Patients had blood samples collected at enrollment, and concentrations of inflammatory biomarkers, including TNFR1, were measured using ELISA at a central laboratory. Enrollment MRI scans were read centrally and interpreted for silent infarcts and burden of WMD using semi-quantitative scales. We compared proportions of patients with prior infarcts and WMD scores across quartiles of TNFR1, and used logistic regression to estimate odds ratios and 95% confidence intervals (OR, 95%CI) to examine the relationship between TNFR1 and subclinical disease after adjusting for demographics and comorbidities. Results: Among 1004 lacunar stroke patients with TNFR1 data (mean age 63.3 ± 10.8 years), 407 (40%) had infarcts besides the qualifying infarct; half the cohort had 0-4 white matter lesions, 27% had 5-8 lesions, and 23% had >=9 lesions. TNFR1 levels were associated with WMD score >=9 (OR per standard deviation (SD) TNFR1=1.2, 95%CI 1.0-1.4). Larger proportions of those in the top quartile of TNFR1, compared to those in the lowest, had ≥9 white matter lesions (29% versus 19%, p=0.026) and additional infarcts (45% versus 37%, p=0.28). After adjusting for demographics and comorbidities, the effect of TNFR1 on WMD score >=9 (adjusted OR per SD=1.1, 95%CI 1.0-1.3) and additional infarcts (adjusted OR 1.2, 95%CI 1.0-1.3) attenuated. Conclusions: Among recent lacunar stroke patients, TNFR1 concentrations were associated with prior or subclinical cerebrovascular disease. Future studies of TNF and TNF inhibitors in cerebral ischemic disease may be warranted.

Non-invasive imaging of oxygen extraction fraction in adults with sickle cell anaemia.

Sickle cell anaemia is a monogenetic disorder with a high incidence of stroke. While stroke screening procedures exist for children with sickle cell anaemia, no accepted screening procedures exist for assessing stroke risk in adults. The purpose of this study is to use novel magnetic resonance imaging methods to evaluate physiological relationships between oxygen extraction fraction, cerebral blood flow, and clinical markers of cerebrovascular impairment in adults with sickle cell anaemia. The specific goal is to determine to what extent elevated oxygen extraction fraction may be uniquely present in patients with higher levels of clinical impairment and therefore may represent a candidate biomarker of stroke risk. Neurological evaluation, structural imaging, and the non-invasive T2-relaxation-under-spin-tagging magnetic resonance imaging method were applied in sickle cell anaemia (n = 34) and healthy race-matched control (n = 11) volunteers without sickle cell trait to assess whole-brain oxygen extraction fraction, cerebral blood flow, degree of vasculopathy, severity of anaemia, and presence of prior infarct; findings were interpreted in the context of physiological models. Cerebral blood flow and oxygen extraction fraction were elevated (P < 0.05) in participants with sickle cell anaemia (n = 27) not receiving monthly blood transfusions (interquartile range cerebral blood flow = 46.2-56.8 ml/100 g/min; oxygen extraction fraction = 0.39-0.50) relative to controls (interquartile range cerebral blood flow = 40.8-46.3 ml/100 g/min; oxygen extraction fraction = 0.33-0.38). Oxygen extraction fraction (P < 0.0001) but not cerebral blood flow was increased in participants with higher levels of clinical impairment. These data provide support for T2-relaxation-under-spin-tagging being able to quickly and non-invasively detect elevated oxygen extraction fraction in individuals with sickle cell anaemia with higher levels of clinical impairment. Our results support the premise that magnetic resonance imaging-based assessment of elevated oxygen extraction fraction might be a viable screening tool for evaluating stroke risk in adults with sickle cell anaemia.

The native T1 in remote myocardium of patients with prior chronic infarction is not normal

The native T1 in remote myocardium of patients with prior chronic infarction is not normal

末梢動脈疾患の有無による薬剤溶出性ステントを用いた冠動脈インターベンション後の長期予後比較：症候性脳梗塞既往患者での検討

末梢動脈疾患の有無による薬剤溶出性ステントを用いた冠動脈インターベンション後の長期予後比較：症候性脳梗塞既往患者での検討

Are daylight saving time transitions associated with changes in myocardial infarction incidence? Results from the German MONICA/KORA Myocardial Infarction Registry.

BackgroundSome studies suggest that transitions to and from daylight saving time (DST) have an influence on acute myocardial infarction (AMI) incidence. However, the available publications have a number of limitations e.g. regarding sample size, exclusion of fatal AMI cases, precise assessment of AMI onset, and consideration of possible confounders, and they were conducted in countries with different geographical location. The objective of this study was to examine the association of DST transitions with AMI incidence recorded in the population-based German MONICA/KORA Myocardial Infarction Registry.MethodsThe study sample consisted of 25,499 coronary deaths and non-fatal AMI cases aged 25–74 years. We used Poisson regression with indicator variables for the 3 days or the week after the spring and the autumn transition and adjusted for potential confounders to model the association between DST transitions and AMI incidence. In addition, we built an excess model by calculating observed over expected events per day.ResultsOverall, no significant changes of AMI risk during the first 3 days or 1 week after the transition to and from DST were found. However, subgroup analyses on the spring transition revealed significantly increased risks for men in the first 3 days after transition (RR 1.155, 95 % CI 1.000–1.334) and for persons who took angiotensine converting enzyme (ACE) inhibitors prior to the AMI (3 days: RR 1.489, 95 % CI 1.151–1.927; 1 week: RR 1.297, 95 % CI 1.063–1.582). After the clock shift in autumn, patients with a prior infarction had an increased risk to have a re-infarction (3 days: RR 1.319, 95 % CI 1.029–1.691; 1 week: RR 1.270, 95 % CI 1.048–1.539).ConclusionsSpecific subgroups such as men and persons with a history of AMI or prior treatment with ACE inhibitors, may have a higher risk for AMI during DST. Further studies which include data on chronotype and sleep duration are needed in order to confirm these results.

Multi-lag HRV analysis discriminates disease progression of post-infarct people with no diabetes versus diabetes.

Diabetes mellitus is associated with multi-organ system dysfunction including the cardiovascular and autonomic nervous system. Although it is well documented that post-infarct patients are at higher risk of sudden cardiac death, diabetes adds an additional risk associated with autonomic neuropathy. However it is not known how the presence of diabetes in post-infarct patients affects cardiac rhythm. The majority of HRV algorithms for determining cardiac inter-beat interval changes describe only beat-to-beat variation determined over the whole heart rate recording and therefore do not consider the ability of a heart beat to influence a train of succeeding beats nor whether or how the temporal dynamics of the inter-beat intervals changes. This study used Poincaré Plot derived features and incorporated increased lag intervals to compare post-infarct patients with no history of prior infarct with or without diabetes and found that for the nondiabetic post-infarct patients only increased lag of short term correlation (SD1) predicted mortality, whereas in the diabetic post-infarct group only long-term correlations (SD2) significantly predicted mortality at a follow-up period of eight years. Temporal dynamics measured as a complex correlation measure (CCM) was also a significant predictor of mortality only in the diabetic post-infarct cohort. This study highlights the different pathophysiological progression and risk profile associated with presence of diabetes in a post-infarct patient population at eight year follow-up.

Diastolic myocardial dysfunction by tissue Doppler imaging predicts mortality in patients with cerebral infarction.

Several clinical prediction score models have been investigated for predicting mortality in patients with cerebral infarction. However, none of these include echocardiographic measures. Our objective was to evaluate the prognostic value of tissue Doppler imaging (TDI) of the myocardium in patients with cerebral infarction. Two hundred forty-four patients with cerebral infarction and subsequent echocardiographic examination in sinus rhythm were identified. Using TDI in three apical projections, longitudinal mitral annular velocities were obtained in six segments. Cox regression models, C-statistics and reclassification analysis were performed for global and segmental e'. During a median follow-up of 3 years 42 patients died. Patients who died had significantly impaired systolic and diastolic function (determined by LVEF and E/e'). The risk of dying increased with decreasing global e', being approximately 13 times higher for patients in the lowest tertile compared to patients in the highest tertile (HR 13.4 [3.2;56.3], p < 0.001). Patients with significantly impaired global e' showed increased mortality after multivariable adjustment for: LVEF, E/e', age, gender, heart failure, chronic obstructive pulmonary disease, prior cerebral infarction, ischemic heart disease, cancer, hypertension, hypercholesterolemia, carotid stenosis, mitral regurgitation, liver disease and thromboembolisms (HR 1.9 [1.1;3.2]), per 1 cm/s decrease, p < 0.05). Similar pattern was seen in segmental analyses of the e'. In contrast to e', no conventional echocardiographic parameters remained independent predictors of mortality after multivariable adjustment. Diastolic myocardial dysfunction determined as e' by TDI is a significant predictor of mortality in patients with cerebral infarction. Applying this parameter can aid the prognostic assessment after cerebral infarction.

Consistency of benefit from an early invasive strategy after fibrinolysis: a patient-level meta-analysis

BackgroundRandomised controlled trials have demonstrated improved outcomes with an early invasive strategy compared with routine care after fibrinolysis among patients with ST-elevation myocardial infarction. However, it remains uncertain whether specific...

Meta-analysis of admission hyperglycaemia in acute myocardial infarction patients treated with primary angioplasty: a cause or a marker of mortality?

Admission hyperglycaemia (AH) has been associated with worse outcomes in acute myocardial infarction (AMI). In the current review, we evaluated the impact of primary angioplasty (pPCI) on mortality in AMI patients with AH. Our second aim was to evaluate if AH is a marker of baseline risk or an independent predictor of mortality. A comprehensive search of four major databases was performed. We included original research studies reporting data on mortality in AMI patients with AH (mean plasma glucose >156 mg/dL/8.7 mmol) and euglycaemia who were treated with pPCI. Of 481 citations, 12 studies were included in the analysis. Admission hyperglycaemia was associated with a higher 30-day [risk ratio (RR) 4.30, P < 0.0001] and 1- to 3-year mortality (RR 2.26, P < 0.0001). As well, AH was more prevalent in women and in patients with an increasing number of cardiac risk factors or angiographic predictors of mortality, such as previous AMI (RR 0.89, P = 0.01), multivessel coronary disease (RR 0.72, P = 0.0001), and involvement of left anterior descending artery (RR 0.92, P < 0.0001). Moreover, patients with AH had larger infarcts (higher creatine kinase-MB; P = 0.004) and more frequent ventricular arrhythmias (P = 0.002). Despite rapid revascularization and treatment of hyperglycaemia, patients with AH continue to have a higher mortality. Admission hyperglycaemia occurs more commonly in patients who have traditional predictors of worse outcomes-specifically prior infarction, anterior wall infarctions, and multivessel disease. Likely, AH is a predictor of rather than a bona fide therapeutic target in AMI.

Mouse SIRT3 attenuates hypertrophy-related lipid accumulation in the heart through the deacetylation of LCAD.

Cardiac hypertrophy is an adaptive response to pressure, volume stress, and loss of contractile mass from prior infarction. Metabolic changes in cardiac hypertrophy include suppression of fatty acid oxidation and enhancement of glucose utilization, which could result in lipid accumulation in the heart. SIRT3, a mitochondrial NAD+-dependent deacetylase, has been demonstrated to play a crucial role in controlling the acetylation status of many enzymes participating in energy metabolism. However, the role of SIRT3 in the pathogenesis of hypertrophy-related lipid accumulation remains unclear. In this study, hypertrophy-related lipid accumulation was investigated using a mouse cardiac hypertrophy model induced by transverse aortic constriction (TAC). We showed that mice developed heart failure six weeks after TAC. Furthermore, abnormal lipid accumulation and decreased palmitate oxidation rates were observed in the hypertrophic hearts, and these changes were particularly significant in SIRT3-KO mice. We also demonstrated that the short form of SIRT3 was downregulated in wild-type (WT) hypertrophic hearts and that this change was accompanied by a higher acetylation level of long-chain acyl CoA dehydrogenase (LCAD), which is a key enzyme participating in fatty acid oxidation. In addition, SIRT3 may play an essential role in attenuating lipid accumulation in the heart through the deacetylation of LCAD.

Comparison of Long-Term Clinical Outcomes after Drug-Eluting Stent Implantation in Patients with Coronary Artery Disease with and without Prior Cerebral Infarction.

To compare the clinical and angiographic outcomes after implantation of drug-eluting stents (DESs) in patients with coronary artery disease (CAD) with or without prior cerebral infarction. Ninety-eight consecutive patients (130 lesions) who underwent successful coronary DES implantation were prospectively classified into two groups: those with a clinical history of symptomatic cerebral infarction (cerebral infarction group, 49 patients, 69 lesions) and those without a clinical history of symptomatic cerebral infarction (noncerebral infarction group, 49 patients, 61 lesions). The primary endpoint was defined as death, nonfatal myocardial infarction, and cerebrovascular events. The Kaplan-Meier method was used to create a primary endpoint curves to determine the time-dependent cumulative primary endpoint-free rate, which were compared using the log-rank test. The incidence of primary endpoints was higher in the cerebral infarction group than in the noncerebral infarction group (p = 0.0075). The Cox proportional hazards regression model for primary endpoint identified prior cerebral infarction (p = 0.0331, hazard ratio = 2.827) and patients with peripheral artery disease (p = 0.0271, hazard ratio = 2.757) as explanatory factors. The results showed that clinical outcomes were poorer in patients with CAD who had prior cerebral infarctions than in those who did not have infarction.

Impact of Intracranial Artery Disease and Prior Cerebral Infarction on Central Nervous System Complications After Off-Pump Coronary Artery Bypass Grafting

We tried to determine whether postoperative CNS complications after off-pump coronary artery bypass grafting (OPCABG) are related to prior cerebral infarction or intracranial artery disease. Fiftyfive patients (among them, 40 men; mean age 64.6 ± 8.9 years) subjected to OPCABG underwent neurological and neuropsychological examinations 24 h before surgery. MRI was used to identify old and/or new ischemic lesions before surgery, and MRA was used to determine the presence and severity of intracranial artery disease. The patients were examined eight days after surgery; possible development of stroke or cognitive dysfunction was evaluated. Associations between postoperative stroke and potential predictors, including prior cerebral infarction and intracranial artery disease, were analyzed using univariate methods. Two of 55 (3.64%) patients had postoperative stroke, and no patient showed cognitive decline. Univariate analysis found no significant association between postoperative stroke and prior cerebral infarction detected by MRI (P = 0.378) or intracranial artery disease detected by MRA (P = 0.103). Our results suggest that intracranial artery disease and prior cerebral infarction are not independent risk factors for stroke after OPCABG. Nonetheless, further investigation of these associations is necessary.

ASSA14-06-01 Is Long-term Warfarin TherapyNecessary in Patients With Mitral Bioprosthetic Valves Plus Atrial Fibrillation?

<h3>Background</h3> Thromboembolism is a major complication after bioprosthectic mitral valve replacement (BMVR) in patients with atrial fibrillation (AF). The antithrombotic therapy in current guideline lacks evidence. <h3>Objectives</h3> A retrospective study was conducted to investigate the efficacy of long-term warfarin or aspirin therapy in patients with AF after BMVR. <h3>Methods</h3> A total of 126 patients presenting with persistent AF underwent BMVR were given anticoagulation therapy with warfarin for 3 months, following warfarin or aspirin therapy according to the surgeon9s preference. The patients were followed up by telephone or mail for postoperative condition, cerebravascular and bleeding events. <h3>Results</h3> 117 (92.9%) patient’s detailed data was available, of which 5 died within 3 months for heart failure, 1 for cerebral infarction and 1 for sudden death. The remaining 112 patients were divided into two groups: Aspirin group (61 patients) and Warfarin group (51 patients). Two groups had similar incidence of cerebral infarction or transient ischaemic attack (TIA) (11.8% vs 14.8%, p = 0.644) and bleeding events (11.8% vs 6.6%, p = 0.336). Each group had one intracranial haemorrhage. 11 patients were dead after three months after surgery, 4 (7.8%) in the Warfarin group and 7 (11.5%) in Aspirin group (p = 0.520 by fisher exact test, p = 0.952 by Kaplan–Meier survival analysis). Univariate analysis demonstrated diabetes, prior cerebral infarction, concomitant CABG and tricuspid valve repair and no left atrial appendage obliteration as risk factors for cerebral infarction and TIA. <h3>Conclusions</h3> In current era in china, antithrombotic therapy with warfarin or aspirin had no significant different impact on long-term prognosis after 3 months anticoagulation with warfarin in patients with AF undergoing BMVR.

Predictive power of late gadolinium enhancement for myocardial recovery in chronic ischaemic heart failure: a HEART sub-study.

The amount of myocardial scar measured by late gadolinium enhancement (LGE) cardiovascular magnetic resonance (CMR) imaging predicts regional recovery in wall motion following revascularization. Previous studies have been conducted in patients with a relatively recent myocardial insult and relatively preserved left ventricular (LV) function. In this sub-study of a clinical trial, the predictive value of LGE, and other CMR-derived data, for myocardial recovery in patients with chronic severe ischaemic cardiomyopathy was assessed. Twenty-two patients with severe LV impairment of ischaemic origin were enrolled as a sub-study of a trial that randomly assigned patients to revascularization or not in addition to guideline-indicated pharmacological therapy. Patients underwent a CMR study at baseline and 6 months. Scans were qualitatively and quantitatively assessed for wall motion, rest/stress myocardial perfusion, and LGE. The median duration of heart failure was 13 (inter-quartile range 5-21) months. Patients had severe LV dilatation [end-diastolic volume (EDV) 280 ± 77 mL] and reduction in LV ejection fraction (LVEF) (29 ± 10%). The percentage scar burden by LGE was 17 ± 9%. Patient characteristics of those undergoing revascularization (n = 7) or not (n = 14) were similar. Myocardial perfusion reserve index (MPRI) improved following revascularization (MPRI 1.17 vs. 1.57, P < 0.0001) but not following medical therapy (1.39 vs. 1.32, P = 0.54). However, LVEF improved in patients whether or not they had revascularization. In the revascularization group, 14% of dysfunctional segments with LGE <25% and 22% of dysfunctional segments with LGE <50% had improved contractile function. However, the transmural extent of LGE did not predict contractile recovery following revascularization or pharmacological therapy (P = 0.19, P = 0.42). LVEDV improved overall (280 ± 77 to 269 ± 83 mL, P = 0.05); improvement was associated with heart failure duration (P = 0.04). In patients with chronic severe LV impairment of ischaemic origin, duration of heart failure is a better predictor of recovery than transmural extent of LGE, following medical therapy or successful revascularization. This suggests that the extent of myocardial remodelling is more important for LV recovery than the presence and extent of prior infarction alone and that LGE should not be the sole determinant of treatment method in severe LV systolic dysfunction of ischaemic origin.

New generation drug‐eluting stents for ST‐elevation myocardial infarction: A new paradigm for safety

The objective of this study is to compare the long-term safety of new generation drug-eluting stents (DES) with early generation DES and bare metal stents (BMS) for ST-segment elevation myocardial infarction (STEMI). Early generation DES for STEMI have reduced target vessel revascularization, but have more very late ST compared with BMS raising concerns about their safety. New compared with early generation DES have lower rates of ST, but there are limited data in STEMI patients. From 2003 to 2011, 3,464 STEMI patients were treated with BMS (n = 1,187), early generation DES (n = 1,525), or new generation DES (n = 752) and were followed for 1-9 years. Patients with new generation DES were younger, had less cardiogenic shock, and less prior infarction versus BMS, and more hypertension versus early generation DES. At 2 years, new generation DES had lower mortality (4.0% vs. 12.4%, P < 0.001), similar reinfarction (4.4% vs. 5.1%, P = 0.35), and less ST (1.4% vs. 3.8%, P = 0.031) versus BMS; and similar mortality (4.0% vs. 5.8%, P = 0.23), similar reinfarction (4.4% vs. 5.2%, P = 0.64), and trends for less ST (1.4% vs. 3.3%, P = 0.17) versus early generation DES. By Cox multivariable analyses, BMS had more ST than new generation DES (HR [95% CI] = 1.93 [1.01-3.66], P = 0.045). New generation DES in STEMI patients have less ST compared to BMS and trends for less ST compared to early generation DES. These data suggest a new safety paradigm and should encourage the use of new generation DES in most STEMI patients treated with primary percutaneous coronary intervention (PCI).

Preoperative Risk Factors in 10,418 Patients With Prior Myocardiac Infarction and 5241 Patients With Previous Unstable Angina Undergoing Elective Coronary Artery Bypass Graft Surgery

Preoperative Risk Factors in 10,418 Patients With Prior Myocardiac Infarction and 5241 Patients With Previous Unstable Angina Undergoing Elective Coronary Artery Bypass Graft Surgery

The clinical profile and pathophysiology of atrial fibrillation: relationships among clinical features, epidemiology, and mechanisms.

Atrial fibrillation (AF) is the most common arrhythmia (estimated lifetime risk, 22%-26%). The aim of this article is to review the clinical epidemiological features of AF and to relate them to underlying mechanisms. Long-established risk factors for AF include aging, male sex, hypertension, valve disease, left ventricular dysfunction, obesity, and alcohol consumption. Emerging risk factors include prehypertension, increased pulse pressure, obstructive sleep apnea, high-level physical training, diastolic dysfunction, predisposing gene variants, hypertrophic cardiomyopathy, and congenital heart disease. Potential risk factors are coronary artery disease, kidney disease, systemic inflammation, pericardial fat, and tobacco use. AF has substantial population health consequences, including impaired quality of life, increased hospitalization rates, stroke occurrence, and increased medical costs. The pathophysiology of AF centers around 4 general types of disturbances that promote ectopic firing and reentrant mechanisms, and include the following: (1) ion channel dysfunction, (2) Ca(2+)-handling abnormalities, (3) structural remodeling, and (4) autonomic neural dysregulation. Aging, hypertension, valve disease, heart failure, myocardial infarction, obesity, smoking, diabetes mellitus, thyroid dysfunction, and endurance exercise training all cause structural remodeling. Heart failure and prior atrial infarction also cause Ca(2+)-handling abnormalities that lead to focal ectopic firing via delayed afterdepolarizations/triggered activity. Neural dysregulation is central to atrial arrhythmogenesis associated with endurance exercise training and occlusive coronary artery disease. Monogenic causes of AF typically promote the arrhythmia via ion channel dysfunction, but the mechanisms of the more common polygenic risk factors are still poorly understood and under intense investigation. Better recognition of the clinical epidemiology of AF, as well as an improved appreciation of the underlying mechanisms, is needed to develop improved methods for AF prevention and management.

Safety of Intravenous Tissue Plasminogen Activator Administration with Computed Tomography Evidence of Prior Infarction

Prior stroke within 3 months excludes patients from thrombolysis; however, patients may have computed tomography (CT) evidence of prior infarct, often of unknown time of origin. We aimed to determine if the presence of a previous infarct on pretreatment CT is a predictor of hemorrhagic complications and functional outcomes after the administration of intravenous (IV) tissue plasminogen activator (tPA). We retrospectively analyzed consecutive patients treated with IV tPA at our institution from 2009-2011. Pretreatment CTs were reviewed for evidence of any prior infarct. Further review determined if any hemorrhagic transformation (HT) or symptomatic intracerebral hemorrhage (sICH) were present on repeat CT or magnetic resonance imaging. Outcomes included sICH, any HT, poor functional outcome (modified Rankin Scale score of 4-6), and discharge disposition. Of 212 IV tPA-treated patients, 84 (40%) had evidence of prior infarct on pretreatment CT. Patients with prior infarcts on CT were older (median age, 72 versus 65 years; P=.001) and had higher pretreatment National Institutes of Health Stroke Scale scores (median, 10 versus 7; P=.023). Patients with prior infarcts on CT did not experience more sICH (4% versus 2%; P=.221) or any HT (18% versus 14%; P=.471). These patients did have a higher frequency of poor functional outcome at discharge (82% versus 50%; P<.001) and were less often discharged to home or inpatient rehabilitation center (61% versus 73%; P=.065). Visualization of prior infarcts on pretreatment CT did not predict an increased risk of sICH in our study and should not be viewed as a reason to withhold systemic tPA treatment after clinically evident strokes within 3 months were excluded.

Myocardial hydrophilic polymer emboli following cardiac catheterization: a case report and literature review

Intravascular polymer emboli have been reported in the skin, lungs, and brain following vascular procedures utilizing hydrophilic polymer coated devices. The Cook arterial introducer sheath was the first of these devices to be introduced, after which case reports followed documenting sterile inflammation at the sheath access site, characterized histologically by perivascular granulomas containing hydrophilic polymer. More recently, hydrophilic polymer emboli have been reported in the vessels of the lungs and brain in association with ischemia and infarct following vascular procedures using polymer coated devices. We report a case of intravascular myocardial emboli associated with acute myocardial infarction following cardiac catheterization. The patient was a 65-year-old man who received cardiac catheterization with placement of a bare metal stent following myocardial infarction. One month later, the patient presented with angina and died shortly after admission. Autopsy revealed hemopericardium with rupture of the left ventricle through an aneurismal defect within the area of prior infarction. Microscopically, an area of acute infarction was present within the aneurismal defect. Numerous small and medium-sized vessels within the left ventricle were occluded by basophilic amorphous granular material with an inflammatory giant cell response. The emboli were most frequent in the area of acute infarction, suggesting that the emboli may have resulted in ischemia leading to the patient's death. This is the third documented case of intramyocardial polymer emboli following cardiac catheterization and the first case to our knowledge to document an association between intravascular myocardial polymer emboli and acute myocardial infarction.