Use of SAMe-TT2R2 in a racially diverse anticoagulation clinic: prediction of optimal anticoagulation.

The SAMe-TT2R2 score predicts optimal long-term oral Vitamin K Antagonist (VKA) anticoagulation for homogenous Caucasian and homogenous Asian populations for non-valvular atrial fibrillation but at different score thresholds. The score that predicts optimal VKA anticoagulation in significantly diverse populations for multiple indications for systemic anticoagulation has not been reported. We determined whether optimal VKA anticoagulation is predicted by SAMe-TT2R2 score in a diverse inner-city population for non-valvular atrial fibrillation (NVAF), unprovoked venous and pulmonary thromboembolic disease (VTE), mechanical prosthetic heart valves and all other indications. All patients on long term VKA's that attended an inner-city anticoagulation clinic between February 2016 and October 2017 were included in this study. Eligible patients were grouped according to oral anticoagulation indication: (1) NVAF, (2) VTE, (3) prosthetic valves and (4) other indications. Each patient's SAMe-TT2R2 score and percent time of INR in the therapeutic range (TTR) was calculated with optimal international normalized ratio (INR) control defined as TTR ≥ 65%. The correlation between SAMe-TT2R2 score and TTR was determined by logistic regression for each oral anticoagulant indication. Receiver operating characteristic curves were then used to identify the best cutoff for prediction of ≥ 65% TTR. Of 316 patients meeting study criteria, 54% were non-Caucasian and there was a significant negative correlation between the SAMe-TT2R2 score and TTR (coefficient - 0.35, P < 0.0001) for all patients. A SAMe-TT2R2 score < 4 was identified as the best threshold for predicting optimal TTR (Youden's J-statistics = 0.238) with accuracy and positive likelihood ratio of 63.4% and 1.73, respectively. The SAMe-TT2R2 score predicts optimal VKA anticoagulation for systemic anticoagulation for multiple indications in a diverse urban population at a higher score than the original report for non-valvular atrial fibrillation of a cohort where < 10% non-Caucasians.

Left Ventricular Geometry on Transthoracic Echocardiogram and Prognosis after Lacunar Stroke: The SPS3 Trial.

BACKGROUND: The spectrum, prevalence, and prognostic implications of abnormal left ventricular geometry (LVG) in patients with lacunar stroke are unknown. We examined the spectrum of LVG and its relationship with vascular risk factors and outcomes after lacunar stroke. METHODS: LVG was determined with transthoracic echocardiography for 1961 patients with magnetic resonance imaging-verified recent lacunar stroke participating in the Secondary Prevention of Small Subcortical Strokes trial. Multivariable logistic regression and Cox proportional hazards models were used to identify characteristics independently associated with LVG and to estimate risk from abnormal LVG for recurrent stroke and death. RESULTS: Abnormal LVG was present in 77%. Hispanic (odds ratio [OR], 1.4; 95% confidence interval, 1.1-1.8) or black (OR, 2.0; 1.3-2.9) race-ethnicity, diabetes (OR, 1.3; 1.0-1.7), hypertension, impaired renal function (OR, 1.8; 1.2-2.5), intracranial stenosis (OR, 1.5; 1.1-2.1), and abnormal left ventricular function (OR, 2.0; 1.4-3.0) were independently associated with abnormal LVG. Subjects with abnormal LVG also more frequently had advanced manifestations of small-vessel disease specifically previous subcortical infarcts and white matter hyperintensities. After adjusting for assigned treatments, clinical risk factors, and advanced manifestations of small-vessel disease, subjects with abnormal LVG remained at increased risk of stroke recurrence (hazard ratio, 1.5; confidence interval, 1.0-2.4). There was no interaction between LVG and assigned antiplatelet or blood pressure target. Abnormal LVG was not associated with mortality. CONCLUSIONS: LVG consistent with chronic hypertensive changes was highly prevalent and correlated with neuroradiologic manifestations of small-vessel disease in lacunar stroke patients. These results support the constructs that both cerebral small-vessel disease and LVG represent end-organ consequences of chronic hypertension.

Isolated tramadol overdose associated with Brugada ECG pattern.

Tramadol is a commonly prescribed synthetic opioid analgesic. In humans, electrocardiogram (ECG) changes consistent with sodium-channel blockade have not been described in overdoses with tramadol. We report a case of isolated tramadol overdose associated with a Brugada ECG pattern. A review of the literature reveals no previous human cases of tramadol overdose causing ECG changes consistent with sodium-channel blockade. However, in vitro blockade of sodium-channels has been demonstrated with high concentrations of tramadol. Tramadol overdose should be recognized as a cause for the manifestation of a Brugada ECG pattern in the setting of suicidal intoxication.

Warfarin in atrial fibrillation patients with moderate chronic kidney disease.

BACKGROUND AND OBJECTIVES: The efficacy of adjusted-dose warfarin for prevention of stroke in atrial fibrillation patients with stage 3 chronic kidney disease (CKD) is unknown. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Patients with stage 3 CKD participating in the Stroke Prevention in Atrial Fibrillation 3 trials were assessed to determine the effect of warfarin anticoagulation on stroke and major hemorrhage, and whether CKD status independently contributed to stroke risk. High-risk participants (n = 1044) in the randomized trial were assigned to adjusted-dose warfarin (target international normalized ratio 2 to 3) versus aspirin (325 mg) plus fixed, low-dose warfarin (subsequently shown to be equivalent to aspirin alone). Low-risk participants (n = 892) all received 325 mg aspirin daily. The primary outcome was ischemic stroke (96%) or systemic embolism (4%). RESULTS: Among the 1936 participants in the two trials, 42% (n = 805) had stage 3 CKD at entry. Considering the 1314 patients not assigned to adjusted-dose warfarin, the primary event rate was double among those with stage 3 CKD (hazard ratio 2.0, 95% CI 1.2, 3.3) versus those with a higher estimated GFR (eGFR). Among the 516 participants with stage 3 CKD included in the randomized trial, ischemic stroke/systemic embolism was reduced 76% (95% CI 42, 90; P < 0.001) by adjusted-dose warfarin compared with aspirin/low-dose warfarin; there was no difference in major hemorrhage (5 patients versus 6 patients, respectively). CONCLUSIONS: Among atrial fibrillation patients participating in the Stroke Prevention in Atrial Fibrillation III trials, stage 3 CKD was associated with higher rates of ischemic stroke/systemic embolism. Adjusted-dose warfarin markedly reduced ischemic stroke/systemic embolism in high-risk atrial fibrillation patients with stage 3 CKD.

Cardiovascular disease in chronic kidney disease. A clinical update from Kidney Disease: Improving Global Outcomes (KDIGO).

Cardiovascular morbidity and mortality in patients with chronic kidney disease (CKD) is high, and the presence of CKD worsens outcomes of cardiovascular disease (CVD). CKD is associated with specific risk factors. Emerging evidence indicates that the pathology and manifestation of CVD differ in the presence of CKD. During a clinical update conference convened by the Kidney Disease: Improving Global Outcomes (KDIGO), an international group of experts defined the current state of knowledge and the implications for patient care in important topic areas, including coronary artery disease and myocardial infarction, congestive heart failure, cerebrovascular disease, atrial fibrillation, peripheral arterial disease, and sudden cardiac death. Although optimal strategies for prevention, diagnosis, and management of these complications likely should be modified in the presence of CKD, the evidence base for decision making is limited. Trials targeting CVD in patients with CKD have a large potential to improve outcomes.

Characteristics of the amiodarone-warfarin interaction during long-term follow-up.

PURPOSE: Characteristics of the amiodarone-warfarin interaction during long-term follow-up were studied. METHODS: Medical records from patients seen in the anticoagulation clinic at the Hennepin County Medical Center between April 1998 and March 2003 were retrospectively reviewed. Patients were included if they were older than 18 years, used the anticoagulation clinic as their primary clinic for anticoagulation therapy, and were receiving combined amiodarone and warfarin therapy for at least one month. The primary study endpoint was the occurrence of International Normalized Ratios (INRs) of >5 at any time during combined warfarin-amiodarone therapy. The secondary endpoint was the frequency of warfarin dosage changes. RESULTS: A total of 70 patients met study inclusion criteria. Of these 70, 7 had amiodarone started before warfarin initiation. Of the 2434 INR values analyzed, 43% (n = 1043) were in the target therapeutic range, 34% (n = 820) were below target range, and 23% (n = 571) were above target range. A total of 102 INR values (4%) were above 5. The relative risk of having an INR of >5 for patients on concurrent warfarin and amiodarone versus those on warfarin alone was 1.366 (p = 0.005). INRs of >5 were most common during the first 12 weeks of combined therapy, with no subsequent large peaks evident. CONCLUSION: Among patients treated in an anticoagulation clinic, INR values of >5 were most common during the first 12 weeks of combined therapy with amiodarone and warfarin and necessitated reduction in warfarin dosage. No other notable changes in INR or amiodarone or warfarin dosage occurred throughout the remainder of the 80-week study period.

Bigeminal rhythms, common and uncommon mechanisms.

Bigeminy is an often encountered arrhythmia in clinical practice. There are common and uncommon mechanisms for bigeminy. Typical examples are illustrated with their salient electrocardiographic and clinical features. When one encounters a bigeminal rhythm, an awareness of these numerous possibilities will facilitate arriving at the correct diagnosis, which is where quality patient care begins.

Principal atrial fibrillation discharges by the new ACC/AHA/ESC classification.

BACKGROUND: The American College of Cardiology, American Heart Association, and European Society of Cardiology Board (ACC/AHA/ESC) 2001 guidelines for management of patients with atrial fibrillation (AF) include a new classification system consisting of 4 categories: first-detected episode; recurrent paroxysmal (self-terminating); recurrent persistent (requiring cardioversion); and permanent. The frequency of hospital discharges within these categories has not been reported. METHODS: The new classification system was applied to 135 consecutive hospital discharges with a principal diagnosis of AF. RESULTS: Classification of AF in these discharged patients included 74 (55%) with first-detected episode; 28 (21%) with recurrent paroxysmal AF; 17 (13%) with recurrent persistent AF; and 16 (12%) with permanent AF. Hypertension (n = 48; 35%) was the most common primary cause of AF, followed by alcohol related (n = 23; 17%), coronary artery disease (n = 20; 15%), and valvular heart disease (n = 17; 12%). For the 102 patients with first-detected and recurrent paroxysmal AF, 71 (69%) converted spontaneously to normal sinus rhythm within 48 hours of admission. Of the 48 patients with a discharge diagnosis of AF, 32 (67%) were receiving anticoagulation therapy. CONCLUSIONS: Most hospital discharges with a principal diagnosis of AF represent the first-detected episode. Diverse causes contribute to AF, and to examine them would help direct therapy. Importantly, in our analysis, 69% of those patients with first-detected or recurrent paroxysmal AF converted spontaneously to normal sinus rhythm within 48 hours of admission.

Marked differences between patients referred for stress echocardiography and myocardial perfusion imaging studies.

BACKGROUND: Patients referred for stress echocardiography may differ significantly from those referred for stress myocardial perfusion imaging (MPI). Such differences, if present, should be considered when comparing the accuracy and discriminatory performance of these tests. METHODS: We prospectively collected demographic and clinical information on all stress imaging studies performed at our institution between 1998 and 2001. The data were reviewed, summarized, and compared using the t test and chi2 test where appropriate. RESULTS: Of 5320 stress imaging studies performed, 3383 were stress echocardiographies and 1937 were MPI studies. Patients referred for MPI were older (59 vs 54, P < .0001), and more likely to have diabetes (32% vs 20%, P < .0001), prior myocardial infarction (39% vs 15%, P < .0001), and prior revascularization (38% vs 12%, P < .0001). Pharmacologic stress testing was much more common in the MPI group (66% vs 17%, P < .0001). More patients referred for MPI had decreased left ventricular function (23% vs 7%, P < .0001) and abnormal stress test results (41% vs 18%, P < .0001). CONCLUSIONS: Patients with a history of myocardial infarction, revascularization, or higher risk profiles are more likely to be referred for MPI compared to stress echocardiography at our institution. These differences in referral patterns are likely to exist in other centers, and it is reasonable to assume that systematic differences in test selection occur, resulting in patient populations with differing clinical risk profiles. Caution in interpreting analyses comparing the accuracy of stress imaging modalities is appropriate.

Left Ventricular Thrombus.

Left ventricular thrombus (LVT) is a frequent complication in patients with acute anterior myocardial infarction (MI) and in those with dilated cardiomyopathy (DCM). The clinical importance of LVT lies in its potential to embolize. The current treatment of patients with acute MI centers on reperfusion, and although controversial, the incidence of LVT complicating acute anterior MI is probably reduced when compared with historical controls. Nevertheless, stroke continues to be a clinically important complication of acute MI and is most common in patients with anterior MI, in part secondary to embolization of LVT. Therapeutic anticoagulation during acute MI reduces the incidence of LVT, and long-term anticoagulation has been associated with a reduction in recurrent infarction and ischemic stroke, but carries hemorrhagic risk. Primary treatment strategies for patients with acute MI center on reperfusion therapy followed by antiplatelet agents and pharmacologic blockade of abnormal neurohumoral mechanisms. Strategies to prevent stroke following infarction include risk stratification for development of LVT and embolism. For patients with anterior MI, particularly those with apical akinesis or dyskinesis, therapeutic anticoagulation reduces the number of LVT and cardioembolic strokes. However, the absolute number of ischemic strokes prevented with this strategy may only be marginal, given the anticoagulation risk, particularly if antiplatelet agents are used concurrently. An attractive alternative strategy is echocardiographic evaluation following anterior infarction with therapeutic anticoagulation reserved for those with demonstrable thrombus. The efficacy of this strategy, however, never has been proven in a clinical study. Primary prevention of cardioembolic stroke through therapeutic anticoagulation is controversial in patients with DCM; the greatest benefit would be expected for those with severe left ventricular dysfunction. If LVT is detected during the course of MI or DCM, therapeutic anticoagulation is usually indicated with the expectation that the majority of thrombi will resolve without clinical evidence of systemic embolism. Additional therapeutic intervention is rarely needed.