Ali Mehdirad

Effect of coronary artery disease on Doppler-derived parameters of aortic flow during upright exercise

Recent advances in Doppler echocardiography have made possible noninvasive determination of stroke volume, cardiac output and peak ejection velocity at rest. To determine the ability of Doppler to measure these variables and the effect of altered left ventricular (LV) function during upright treadmill exercise, 20 normal subjects (group I) and 17 patients with coronary artery disease (CAD) (group II) were studied. Stroke index response was similar in both groups. The increase in cardiac index was more rapid in group I subjects and reached a higher peak value at maximal exercise (8.6 +/- 2.5 vs 5.5 +/- 2.2 liters/min, p less than 0.001). Peak ejection velocity increased rapidly during exercise in group I subjects; it increased much less in group II patients. Differences were significant at each stage of exercise. Peak ejection velocity was 1.56 +/- 0.32 and 0.89 +/- 0.26 m/s in group I vs group II patients, respectively, at maximal exercise. Three responses were seen in group II subjects. Three patients, all with 1-vessel CAD and normal LV function at rest, showed a normal response, with an increase in peak ejection velocity of at least 80% (type I response). In 8 patients peak ejection velocity increased less than 80% (type II response) and in 6 patients it decreased at maximal exercise (type III). Type II and III responses were seen in patients with more severe CAD and LV dysfunction at rest. These data show a progressive difference in Doppler-derived variables in exercise between normal subjects and patients with CAD, which is greatest in patients with LV dysfunction at rest and multivessel CAD.

Beyond warfarin: A patient-centered approach to selecting novel oral anticoagulants for stroke prevention in atrial fibrillation

BACKGROUND Warfarin reduces stroke in patients with atrial fibrillation. However, its narrow therapeutic index and need for chronic monitoring are barriers to its optimal utilization in many patients. The recent introduction of 3 novel oral anticoagulants (NOACs), as alternatives to warfarin, may change the eligibility and management of patients with nonvalvular atrial fibrillation (NVAF) who require systemic anticoagulation. PURPOSE To summarize contemporary indications for anticoagulation in NVAF, and to help provide patient-centered clinical decision making for selecting warfarin or 1 of the NOACs (dabigatran, rivaroxaban, apixaban) based on randomized trials and mechanistic data for each drug. DATA SOURCES AND STUDY SELECTION The primary clinical outcome trials of warfarin and the NOACs, pharmacologic studies, and briefing documents from the US Food and Drug Administration were reviewed. DATA EXTRACTION AND DATA SYNTHESIS In randomized trials, NOACs were consistently noninferior to warfarin for reducing stroke or systemic embolism in patients with NVAF, with reductions in intracranial bleeding as well. However, NOACs have several important drug-drug interactions, exclusion criteria for specific patient subgroups (eg, severe renal disease), and each medication may have a different impact on other clinical outcomes such as myocardial infarction or gastrointestinal bleeding. Benefits of the new drugs are particularly pronounced when international normalized ratio levels on warfarin are labile. CONCLUSIONS Warfarin continues to play an important role in the prevention of stroke or systemic embolism in NVAF. Among selected patients, the use of NOACs provides equal or superior benefit, without the need for chronic anticoagulation monitoring or ongoing dose titration.

Atrial Fibrillation Monitoring in Cryptogenic Stroke: the Gaps Between Evidence and Practice

Identifying occult paroxysmal atrial fibrillation as the etiology of cryptogenic stroke has been a top research priority in the past decade. This is because prompt initiation of anticoagulation has significantly decreased subsequent stroke risk. Available evidence suggests that prolonged cardiac monitoring after stroke increases the likelihood of detecting atrial fibrillation. However, further research is required to fill in the gaps in regard to the optimal period of monitoring, candidates for monitoring, etc. Here, we review the current evidence supporting the use of prolonged monitoring for cryptogenic stroke patients and discuss the directions of future research.

Impact of the Norepinephrine Prodrug Droxidopa on the QTc Interval in Healthy Individuals

A double‐blind, 4‐period crossover study (NCT01327066) was conducted to assess the effect of the novel norepinephrine prodrug droxidopa on the QT interval in in healthy subjects. Subjects were randomized to receive a single dose of droxidopa 600 mg (maximal dose) and 2000 mg (supratherapeutic dose) compared with the positive control, moxifloxacin 400 mg, and placebo, each separated by a 3‐day washout period. Patients were monitored by continuous Holter monitoring, and electrocardiograms (ECGs) were extracted 0.5–23 hours after dosing. Blood samples for pharmacokinetic analysis were collected before dosing and after ECG data collection. The primary end point was the time‐matched placebo‐adjusted change from baseline in the individually corrected QT (QTcI). The time‐averaged QTcI mean placebo‐corrected changes from baseline for droxidopa 600 and 2000 mg were 0.1 milliseconds (90%CI, ‐0.9 to 1.0 milliseconds) and 0.3 milliseconds (90%CI, ‐0.6 to 1.3 milliseconds), respectively, and 9 milliseconds (90%CI, 8.4–10.3 milliseconds) for moxifloxacin. This study found no effect of either dose of droxidopa on cardiac repolarization using QTcI. Analysis of the pharmacokinetic/pharmacodynamic relationship and cardiac repolarization showed no association with droxidopa exposure. There were no clinically relevant effects of droxidopa on heart rate, atrioventricular conduction, or cardiac depolarization identified. No morphologic ECG changes were observed.

Managing neurogenic orthostatic hypotension with droxidopa in a patient with Parkinson disease, atrial fibrillation, and hypertension

Mr. Y is a 70-year-old man with Parkinson disease (PD) currently taking carbidopa/levodopa 25 mg/100 mg orally three times daily (TID). He has been living at home with his wife of 50 years, can ambulate independently, but has experienced three falls during the last 3 months. He was referred to cardiology for evaluation of syncope. Reportedly, the patient had been in good health. After finishing a long dinner in a restaurant, he stood up to leave. His wife reported that he appeared somewhat dazed, and subsequently ‘‘crumbled to the floor’’. He briefly lost consciousness (\30 s), came to without any neurological deficit, and he sustained no injury. He reported no prodromal symptoms of dizziness, lightheaded, or nausea, and did not appear pale. An echocardiogram 1-year prior demonstrated mild left ventricular hypertrophy, but no systolic or diastolic dysfunction and no evidence of valvular disease. Carotid ultrasound 2 years prior revealed minimal carotid disease and no significant stenosis. His past medical history is significant for atrial fibrillation and a transient ischemic attack (TIA). He is currently taking metoprolol XL 25 mg/day and aspirin 325 mg/day. The patient was determined to have a CHA2DS2-VASc [4] score of 5 (age, hypertension, history of TIA, and carotid disease all contributing to this score), a high-risk status for stroke and systemic embolism for which he was initially prescribed apixaban 5 mg twice daily. He was also taking aspirin 81 mg daily due to the presence of carotid artery disease. However, unfortunately, as a result of frequent falls and concerns for development of injuries (e.g., subdural hematoma), after a thorough discussion with the patient and his family about the benefits and risks of anticoagulation in the patient, apixaban was discontinued and instead aspirin dosage was increased to 325 mg daily.

Erratum to: Titrating droxidopa to maximize symptomatic benefit in a patient with Parkinson disease and neurogenic orthostatic hypotension

The article ‘‘Titrating droxidopa to maximize symptomatic benefit in a patient with Parkinson disease and neurogenic orthostatic hypotension’’, written by Karabin et al., was originally published Online First without open access. After publication in volume 27, issue 1, page S15–S16 the author decided to opt for Open Choice and to make the article an open access publication. Therefore, the copyright of the article has been changed to The Author(s) 2017 and the article is forthwith distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits use, duplication, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.

Successful Treatment of a Cardiac Resynchronization Therapy Nonresponder by Identifying Lead Malpositioning

This case describes some of the commonly overlooked device-related issues in patients who have reportedly failed to respond to cardiac resynchronization therapy (CRT). The case demonstrates voltage-dependent right ventricular capture instead of right atrial capture by a subtly malpositioned right atrial lead. CRT therapy failed to improve symptoms of heart failure and the diagnosis of “CRT nonresponder” was made. With a detailed fact-finding approach, the mechanism behind this nonresponse was identified, and the outcome of CRT was significantly improved with rectification of the problems.

Non-Vitamin K Antagonist Oral Anticoagulants in Atrial Fibrillation: Pharmacology and Phase III Clinical Trials

Atrial fibrillation (AF) is a very common clinically significant arrhythmia noted in clinical practice. Its incidence increases with age and along with advanced age, other risk factors such hypertension, vascular disease, heart failure, diabetes, prior stroke and female sex determine the associated stroke risk with AF. For over 40 years warfarin has been the drug of choice used to reduce this stroke risk associated with AF. However, the narrow therapeutic range, dietary restrictions, and chronic monitoring with warfarin led to the development of novel oral anticoagulants (NOACs) such as dabigatran, rivaroxaban, apixaban, and edoxaban. The purpose of this chapter is to elucidate pharmacology and the clinical performance of these NOACs in the setting of non-valvular atrial fibrillation (NVAF).

A RARE CAUSE OF RECURRENT ORTHOSTATIC HYPOTENSION REFRACTORY TO CONVENTIONAL TREATMENT

Orthostatic hypotension is a common diagnosis encountered in medical practice. Conventional therapies, including correcting reversible causes, non-pharmacologic and pharmacologic treatments usually achieve facile symptom resolution. We herein present a case of neurogenic orthostatic hypotension (NOH

RECURRENT MYOCARDIAL INFARCTION IN THE YOUNG FROM CORONARY THROMBOSIS AS THE FIRST PRESENTATION OF LIFE-CHANGING DIAGNOSIS

Myocardial infarction (MI) in the young is rare. Non-atherosclerosis is the predominant etiology. We herein report a young patient with recurrent MI within 6 weeks, which led to a newly diagnosed Human Immunodeficiency Virus (HIV) infection. A 29-year-old man presented with heartburn symptoms and