Satish R. Raj

Consensus statement on the definition of orthostatic hypotension, neurally mediated syncope and the postural tachycardia syndrome

Roy Freeman • Wouter Wieling • Felicia B. Axelrod • David G. Benditt • Eduardo Benarroch • Italo Biaggioni • William P. Cheshire • Thomas Chelimsky • Pietro Cortelli • Christopher H. Gibbons • David S. Goldstein • Roger Hainsworth • Max J. Hilz • Giris Jacob • Horacio Kaufmann • Jens Jordan • Lewis A. Lipsitz • Benjamin D. Levine • Phillip A. Low • Christopher Mathias • Satish R. Raj • David Robertson • Paola Sandroni • Irwin Schatz • Ron Schondorff • Julian M. Stewart • J. Gert van Dijk

Consensus statement on the definition of orthostatic hypotension, neurally mediated syncope and the postural tachycardia syndrome.

Roy Freeman • Wouter Wieling • Felicia B. Axelrod • David G. Benditt • Eduardo Benarroch • Italo Biaggioni • William P. Cheshire • Thomas Chelimsky • Pietro Cortelli • Christopher H. Gibbons • David S. Goldstein • Roger Hainsworth • Max J. Hilz • Giris Jacob • Horacio Kaufmann • Jens Jordan • Lewis A. Lipsitz • Benjamin D. Levine • Phillip A. Low • Christopher Mathias • Satish R. Raj • David Robertson • Paola Sandroni • Irwin Schatz • Ron Schondorff • Julian M. Stewart • J. Gert van Dijk

2015 Heart Rhythm Society Expert Consensus Statement on the Diagnosis and Treatment of Postural Tachycardia Syndrome, Inappropriate Sinus Tachycardia, and Vasovagal Syncope

Robert S. Sheldon, Blair P. Grubb II, Brian Olshansky, Win-Kuang Shen, Hugh Calkins, Michele Brignole, Satish R. Raj, Andrew D. Krahn, Carlos A. Morillo, Julian M. Stewart, Richard Sutton, Paola Sandroni, Karen J. Friday, Denise Tessariol Hachul, Mitchell I. Cohen, Dennis H. Lau, Kenneth A. Mayuga, Jeffrey P. Moak, Roopinder K. Sandhu, Khalil Kanjwal

2017 ACC/AHA/HRS guideline for the evaluation and management of patients with syncope: A report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines and the Heart Rhythm Society

This document was approved by the American College of Cardiology Cli American Heart Association Science Advisory and Coordinating Committe Rhythm Society Board of Trustees in January 2017. The American College of Cardiology requests that this document be cite Goldberger ZD, Grubb BP, Hamdan MH, Krahn AD, Link MS, Olshansky B guideline for the evaluation and management of patients with syncope: a rep Force on Clinical Practice Guidelines and the Heart Rhythm Society. J Am C This article has been copublished in Circulation and HeartRhythm. Copies: This document is available on the World Wide Web sites of the Ame (professional.heart.org), and the Heart Rhythm Society (www.hrsonline.o Department via fax (212-633-3820) or e-mail (reprints@elsevier.com). Permissions: Multiple copies, modification, alteration, enhancement, and permission of the American College of Cardiology. Requests may be compl author-agreement/obtaining-permission). Satish R. Raj, MD, MSC, FACC, FHRS*x Roopinder Kaur Sandhu, MD, MPHz Dan Sorajja, MDz Benjamin C. Sun, MD, MPP, FACEPk Clyde W. Yancy, MD, MSC, FACC, FAHAz{

Altered Systemic Hemodynamic and Baroreflex Response to Angiotensin II in Postural Tachycardia Syndrome

Background— Postural tachycardia syndrome (POTS) is characterized by excessive orthostatic tachycardia and significant functional disability. We have previously found that patients with POTS have increases in plasma angiotensin II (Ang II) that are twice as high as healthy subjects despite normal blood pressures (BPs). In this study, we assess systemic and renal hemodynamic and functional responses to Ang II infusion in patients with POTS compared with healthy controls. Methods and Results— Following a 3-day sodium-controlled diet, we infused Ang II (3 ng/kg per minute) for 1 hour in patients with POTS (n=15) and healthy controls (n=13) in the supine position. All study subjects were women with normal BP. Ages were similar for patients with POTS and controls (mean±SEM, 30±2 versus 26±1 years; P=0.11). We measured the changes from baseline mean arterial pressure, renal plasma flow, plasma renin activity, aldosterone, urine sodium, and baroreflex sensitivity in both groups. In response to Ang II infusion, patients with POTS had a blunted increase compared with controls in mean arterial pressure (10±1 versus 14±1 mm Hg, P=0.01) and diastolic BP (9±1 versus 13±1 mm Hg, P=0.01) but not systolic BP (13±2 versus 15±2 mm Hg, P=0.40). Renal plasma flow decreased similarly with Ang II infusion in patients with POTS versus controls (−166±20 versus −181±17 mL/min per 1.73 kg/m2, P=0.58). Postinfusion, the decrease in plasma renin activity (−0.9±0.2 versus −0.6±0.2 ng/mL per hour, P=0.43) and the increase in aldosterone (17±1 versus 15±2 pg/mL, P=0.34) were similar in both groups. The decrease in urine sodium excretion was similar in patients with POTS and controls (−49±12 versus −60±16 mEq/g creatinine, P=0.55). The spontaneous baroreflex sensitivity at baseline was significantly lower in patients with POTS compared with controls (10.1±1.2 versus 16.8±1.5 ms/mm Hg, P=0.003), and it was further reduced with Ang II infusion. Conclusions— Patients with POTS have blunted vasopressor response to Ang II and impaired baroreflex function. This impaired vasoconstrictive response might be exaggerated with upright posture and may contribute to the subsequent orthostatic tachycardia that is the hallmark of this disorder. Clinical Trial Registration— URL: http://www.clinicaltrials.gov. Unique identifier: NCT00962949.

Neurally Mediated Syncope

Publisher Summary Syncope is a sudden, transient loss of consciousness with spontaneous recovery that is associated with the loss of postural tone. Neurally mediated syncope (NMS or reflex fainting) is the most common cause of syncope, especially in those patients without the evidence of structural heart disease. NMS most commonly occurs after prolonged sitting or standing, although it can also occur with exercise or emotional/ psychological triggers. The most common explanation for NMS is known as the “Ventricular Hypothesis.” This hypothesis provides a plausible explanation for the “postural prodrome” to many of the episodes of NMS. It also provides a rationale for the use of the tilt-table test, which is commonly used to aid the diagnosis of NMS. The history and the physical examination are at the heart of the diagnosis of NMS. The physical examination should focus on ruling out structural heart disease and focal neurologic lesions. The most useful examination maneuver is the carotid sinus massage. The technique involves performing up to 10 seconds of massage to the carotid sinus (per side) in both the supine and the upright posture, with a positive result requiring a decrease in blood pressure or heart rate with an associated reproduction in presenting symptoms.

Clinical challenges in the diagnosis and management of postural tachycardia syndrome

Postural tachycardia syndrome (POTS) is a multifactorial clinical syndrome defined by an increase in heart rate of ≥30 bpm on standing from supine position (or ≥40 bpm in children). It is associated with symptoms of cerebral hypoperfusion that are worse when upright and improve when in supine position. Patients often have additional symptoms including severe fatigue and difficulty concentrating. There are several possible pathophysiologic mechanisms including hypovolaemia, small-fibre peripheral neuropathy and hyperadrenergic states. POTS can also be associated with several disorders including mastocytosis, Ehlers-Danlos syndrome (hypermobility type) and autoimmune disorders. The treatment is focused on symptom relief and not solely on reducing tachycardia. Given its varying presentations, it is important to employ a practical, mechanism-focused approach to the diagnosis and management of POTS.

Assessing physician knowledge regarding indications for a primary prevention implantable defibrillator and potential barriers for referral

Although there is clear evidence to demonstrate that primary prevention implantable defibrillators (ICDs) reduce mortality in high‐risk patients, ICDs are underutilized. Limited data exist assessing referring physicians’ knowledge about guideline indications and attitudes towards ICDs, which may influence decision for referral.

Orthostatic Hypotension After Continuous-Flow Left Ventricular Assist Device Implantation in a Patient With Longstanding Diabetes Mellitus

A continuous-flow left ventricular assist device (CF-LVAD) benefits patients with advanced heart failure as a bridge to cardiac transplantation. However, unanticipated complications may occur. We report a patient with end-stage heart failure and longstanding diabetes who experienced functionally debilitating orthostatic hypotension from autonomic insufficiency after CF-LVAD implantation. This case demonstrates a role for comprehensive autonomic function testing in the workup of orthostatic hypotension after LVAD implantation.

Hyperinsulinemia and Insulin Resistance in Dopamine β-Hydroxylase Deficiency

Context Dopamine β-hydroxylase (DBH) deficiency is a rare genetic disorder characterized by failure to convert dopamine to norepinephrine. DBH-deficient patients lack sympathetic adrenergic function and are therefore predisposed to orthostatic hypotension. DBH-deficient mice exhibit hyperinsulinemia, lower plasma glucose levels, and insulin resistance due to loss of tonic sympathetic inhibition of insulin secretion. The impact of DBH deficiency on glucose homeostasis in humans is unknown. Case Description We describe the metabolic profile of an adolescent female DBH-deficient patient. The patient underwent genetic testing, cardiovascular autonomic function testing, and evaluation of insulin secretion and sensitivity with hyperglycemic clamp under treatment-naive conditions. All procedures were repeated after 1 year of treatment with the norepinephrine prodrug droxidopa (300 mg, 3 times a day). Genetic testing showed a homozygous mutation in the DBH gene (rs74853476). Under treatment-naive conditions, she had undetectable plasma epinephrine and norepinephrine levels, resulting in sympathetic noradrenergic failure and orthostatic hypotension (-32 mm Hg supine to seated). She had high adiposity (41%) and fasting plasma insulin levels (25 μU/mL), with normal glucose (91 mg/dL). Hyperglycemic clamp revealed increased glucose-stimulated insulin secretion and insulin resistance. Droxidopa restored plasma norepinephrine and improved orthostatic tolerance, with modest effects on glucose homeostasis. Conclusions We provide evidence for impairment in cardiovascular autonomic regulation, hyperinsulinemia, enhanced glucose-stimulated insulin secretion, and insulin resistance in a DBH-deficient patient. These metabolic derangements were not corrected by chronic droxidopa treatment. These findings provide insight into the pathophysiology and treatment of DBH deficiency and into the importance of catecholaminergic mechanisms to resting metabolism.