Faculty Bibliography

Background. Takotsubo cardiomyopathy is defined as a transient left ventricular dysfunction, usually accompanied by electrocardiographic changes. The literature documents only two other cases of Takotsubo cardiomyopathy in the latter setting. Methods. A 78-year-old female presented to the ED with severe shortness of breath, hypertension, and tachycardia. On physical exam, heart sounds (S1 and S2) were regular and wheezing was noticed bilaterally. We found laboratory results with a WBC of 20.0 (103/muL), troponin of 16.52 ng/mL, CK-mb of 70.6%, and BNP of 177 pg/mL. The patient was intubated for acute hypoxemic respiratory failure. A chest X-ray revealed a large left-sided tension pneumothorax. Initial echocardiogram showed apical ballooning with a LVEF of 10-15%. A cardiac angiography revealed normal coronary arteries with no coronary disease. After supportive treatment, the patient's condition improved with a subsequent echocardiogram showing a LVEF of 60%. Conclusion. The patient was found to have Takotsubo cardiomyopathy in the setting of a tension pneumothorax. The exact mechanisms of ventricular dysfunction have not been clarified. However, multivessel coronary spasm or catecholamine cardiotoxicity has been suggested to have a causative role. We suggest that, in our patient, left ventricular dysfunction was induced by the latter mechanism related to the stress associated with acute pneumothorax.

IMPORTANCE: Epidemiological evidence suggests that physical activity benefits cognition, but results from randomized trials are limited and mixed. OBJECTIVE: To determine whether a 24-month physical activity program results in better cognitive function, lower risk of mild cognitive impairment (MCI) or dementia, or both, compared with a health education program. DESIGN, SETTING, AND PARTICIPANTS: A randomized clinical trial, the Lifestyle Interventions and Independence for Elders (LIFE) study, enrolled 1635 community-living participants at 8 US centers from February 2010 until December 2011. Participants were sedentary adults aged 70 to 89 years who were at risk for mobility disability but able to walk 400 m. INTERVENTIONS: A structured, moderate-intensity physical activity program (n = 818) that included walking, resistance training, and flexibility exercises or a health education program (n = 817) of educational workshops and upper-extremity stretching. MAIN OUTCOMES AND MEASURES: Prespecified secondary outcomes of the LIFE study included cognitive function measured by the Digit Symbol Coding (DSC) task subtest of the Wechsler Adult Intelligence Scale (score range: 0-133; higher scores indicate better function) and the revised Hopkins Verbal Learning Test (HVLT-R; 12-item word list recall task) assessed in 1476 participants (90.3%). Tertiary outcomes included global and executive cognitive function and incident MCI or dementia at 24 months. RESULTS: At 24 months, DSC task and HVLT-R scores (adjusted for clinic site, sex, and baseline values) were not different between groups. The mean DSC task scores were 46.26 points for the physical activity group vs 46.28 for the health education group (mean difference, -0.01 points [95% CI, -0.80 to 0.77 points], P = .97). The mean HVLT-R delayed recall scores were 7.22 for the physical activity group vs 7.25 for the health education group (mean difference, -0.03 words [95% CI, -0.29 to 0.24 words], P = .84). No differences for any other cognitive or composite measures were observed. Participants in the physical activity group who were 80 years or older (n = 307) and those with poorer baseline physical performance (n = 328) had better changes in executive function composite scores compared with the health education group (P = .01 for interaction for both comparisons). Incident MCI or dementia occurred in 98 participants (13.2%) in the physical activity group and 91 participants (12.1%) in the health education group (odds ratio, 1.08 [95% CI, 0.80 to 1.46]). CONCLUSIONS AND RELEVANCE: Among sedentary older adults, a 24-month moderate-intensity physical activity program compared with a health education program did not result in improvements in global or domain-specific cognitive function. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01072500.

Portal vein thrombosis (PVT) is the blockage or narrowing of the portal vein by a thrombus. It is relatively rare and has been linked with the presence of an underlying liver disease or prothrombotic disorders. We present a case of a young male who presented with vague abdominal symptoms for approximately one week. Imaging revealed the presence of multiple nonocclusive thrombi involving the right portal vein, the splenic vein, and the left renal vein, as well as complete occlusion of the left portal vein and the superior mesenteric vein. We discuss pathogenesis, clinical presentation, and management of both acute and chronic thrombosis. The presence of PVT should be considered as a clue for prothrombotic disorders, liver disease, and other local and general factors that must be carefully investigated. It is hoped that this case report will help increase awareness of the complexity associated with portal vein thrombosis among the medical community.

BACKGROUND: In Phase 3 double-blind trials (MS-F203 and MS-F204), dalfampridine extended release tablets 10 mg twice daily (dalfampridine-ER; prolonged-release fampridine in Europe; fampridine modified or sustained release elsewhere) improved walking speed relative to placebo in patients with multiple sclerosis (MS). OBJECTIVES: Evaluation of long-term safety and efficacy of dalfampridine-ER in open-label extensions (MS-F203EXT, MS-F204EXT). METHODS: Patients received dalfampridine-ER 10 mg twice daily; and had Timed 25-Foot Walk (T25FW) assessments at 2, 14 and 26 weeks, and then every 6 months. Subjects were categorized as dalfampridine-ER responders or non-responders, based on their treatment response in the double-blind parent trials that assessed T25FW. RESULTS: We had 269 patients enter MS-F203EXT and 154 patients complete it; for a maximum exposure of 5 years. We had 214 patients enter MS-F204EXT and 146 complete it; for a maximum exposure of 3.3 years. No new safety signals emerged and dalfampridine-ER tolerability was consistent with the double-blind phase. Improvements in walking speed were lost after dalfampridine-ER was discontinued in the parent trial, but returned by the 2-week assessment after re-initiation of the drug. Throughout the extensions, mean improvement in walking speed declined, but remained improved, among the double-blind responders as compared with non-responders. CONCLUSIONS: The dalfamipridine-ER safety profile was consistent with the parent trials. Although walking speed decreased over time, dalfampridine-ER responders continued to show improved walking speed, which was sustained compared with non-responders.

BACKGROUND: Two phase 3 clinical trials demonstrated that dalfampridine extended-release 10-mg tablets (D-ER), twice daily, significantly improved walking relative to placebo in patients with multiple sclerosis (MS). The objective of this study was to evaluate the efficacy and safety of D-ER in patients with MS using pooled data from the two phase 3 trials. METHODS: Data were pooled from the two trials, and D-ER was compared with placebo for timed-walk responder rate, changes in walking speed, and the 12-item Multiple Sclerosis Walking Scale (MSWS-12). Response rates were evaluated with respect to demographic and clinical characteristics. RESULTS: D-ER had a significantly higher proportion of timed-walk responders relative to placebo (37.6% vs. 8.9%; P < .0001). The responder rate was independent of age, gender, race, body-mass index, type of MS, duration of MS, baseline Expanded Disability Status Scale score, baseline walking speed, and concomitant use of immunomodulatory therapies. Significant improvements were observed in walking speed and in MSWS-12 score for the pooled D-ER group compared with placebo. The safety profile was consistent with the individual studies; no new safety or tolerability concerns were identified. CONCLUSIONS: D-ER demonstrated efficacy for the improvement of walking in patients with MS; response was independent of demographic and clinical characteristics.

Walking impairment is a clinical hallmark of multiple sclerosis (MS). Dalfampridine-ER, an extended-release formulation of dalfampridine (also known by its chemical name, 4-aminopyridine, and its international nonproprietary name, fampridine), was developed to maintain drug plasma levels within a narrow therapeutic window, and assessed for its ability to improve walking in MS. The putative mechanism of action of dalfampridine-ER is restoration of axonal conduction via blockade of the potassium channels that become exposed during axonal demyelination. Two pivotal phase III clinical trials demonstrated that dalfampridine-ER 10-mg tablets administered twice daily improved walking speed and patient-reported perceptions of walking in some patients. Dalfampridine-ER was generally well tolerated, and, at the approved dose, risk of seizure was neither elevated relative to placebo nor higher than the rate in the MS population. Dalfampridine-ER (AMPYRA(R)) was approved in the United States for the treatment of walking in patients with MS as demonstrated by an increase in walking speed. The use of the dalfampridine-ER is contraindicated in patients with a history of seizure. It is the first pharmacologic therapy for this indication and has been incorporated into clinical management of MS.

Peripartum cardiomyopathy is a life-threatening cardiac condition affecting pregnant women either late in pregnancy or early in the post-partum period. The latest studies show a dramatic improvement in the mortality rates of women affected with this disorder, which has been correlated with advances in medical therapy for heart failure. However, patients continue to die of this condition. The following case report describes a typical patient with peripartum cardiomyopathy diagnosed on clinical grounds, along with echocardiogram findings of severe systolic dysfunction and global hypokinesis consistent with dilated cardiomyopathy. Emergency cesarean delivery had to be performed for fetal distress. There was significant improvement of the patient's condition with standard pharmacological management for heart failure at the time of discharge. However, five weeks after discharge, fatal cardiac arrest occurred. It is hoped that this article will raise awareness about this rare but potentially fatal condition and promote understanding of its main clinical features, diagnostic criteria, and conventional pharmacological management.

The importance of early thrombolysis in acute myocardial infarction has been highlighted in several large trials. The clinical decision is often taken by physicians who need to take a rapid action with the risk of misdiagnosing non-coronary events that mimic myocardial infarction. Here we describe a case of acute pericarditis in a 37-year-old man whom received thrombolysis and developed a sudden hemorrhagic pericardial effusion that evolved rapidly into a cardiac tamponade. These errors leading to lethal thrombolysis complications have been surprisingly rare; but a correct diagnosis of aortic dissection or hemorrhagic pericarditis needs to be stressed because even after obtaining the correct diagnosis, the prolonged disturbance of hemostasis prevents a rapid therapy being instigated.

Objectives: Sudden cardiac death in the dialysis population comprises 25% of all-cause of mortality. The epicardial approach for cardiac rhythm device leads may be preferred over transvenous leads. Background: The transvenous route has been the most frequently used method for insertion of Cardiac Rhythm Device (CRD) leads. However, this route can cause major problems including central venous stenosis and cardiac device infection during episodes of dialysis access-related bacteremia. Methods: This is a case report where a 56 year-old man on chronic hemodialysis presented with episodes of cardiac arrest due to ventricular fibrillation. He had had an amputation due to osteomyelitis and an arteriovenous-graft (AVG) infection of the right upper extremity in the past. At present evaluation he had a left upper extremity AVG. Results: Vascular evaluation revealed right subclavian vein and superior vena cava stenoses. Along with the presence of a left upper extremity AVG, this posed a dilemma regarding safety and usefulness of a transvenous rhythm device. An ERD-AICD was placed and one year later there were no cardiac or infectious events reported. Conclusions: Epicardial leads should be considered in hemodialysis patients who require a new CRD or replacement of existing transvenous CRD leads. Transvenous CRD leads can cause central venous stenosis and are vulnerable to contamination during AVG or tunneled hemodialysis catheter-related bacteremia. Because these complications are not infrequent in hemodialysis patients an alternative pathway is warranted. Epicardial leads do not traverse through the central veins and are not directly exposed to blood flow and do not cause central venous stenosis