There is, I think, something ethereal about i —the square root of minus one. I remember first hearing about it at school. It seemed an odd beast at that time—an intruder hovering on the edge of reality.

Usually familiarity dulls this sense of the bizarre, but in the case of i it was the reverse: over the years the sense of its surreal nature intensified. It seemed that it was impossible to write mathematics that described the real world in …

I and i

Background Thyrotoxicosis has multiple etiologies, manifestations, and potential therapies. Appropriate treatment requires an accurate diagnosis and is influenced by coexisting medical conditions and patient preference. This document describes evidence-based clinical guidelines for the management of thyrotoxicosis that would be useful to generalist and subspecialty physicians and others providing care for patients with this condition. Methods The American Thyroid Association (ATA) previously cosponsored guidelines for the management of thyrotoxicosis that were published in 2011. Considerable new literature has been published since then, and the ATA felt updated evidence-based guidelines were needed. The association assembled a task force of expert clinicians who authored this report. They examined relevant literature using a systematic PubMed search supplemented with additional published materials. An evidence-based medicine approach that incorporated the knowledge and experience of the panel was used to update the 2011 text and recommendations. The strength of the recommendations and the quality of evidence supporting them were rated according to the approach recommended by the Grading of Recommendations, Assessment, Development, and Evaluation Group. Results Clinical topics addressed include the initial evaluation and management of thyrotoxicosis; management of Graves' hyperthyroidism using radioactive iodine, antithyroid drugs, or surgery; management of toxic multinodular goiter or toxic adenoma using radioactive iodine or surgery; Graves' disease in children, adolescents, or pregnant patients; subclinical hyperthyroidism; hyperthyroidism in patients with Graves' orbitopathy; and management of other miscellaneous causes of thyrotoxicosis. New paradigms since publication of the 2011 guidelines are presented for the evaluation of the etiology of thyrotoxicosis, the management of Graves' hyperthyroidism with antithyroid drugs, the management of pregnant hyperthyroid patients, and the preparation of patients for thyroid surgery. The sections on less common causes of thyrotoxicosis have been expanded. Conclusions One hundred twenty-four evidence-based recommendations were developed to aid in the care of patients with thyrotoxicosis and to share what the task force believes is current, rational, and optimal medical practice.

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2016 American Thyroid Association Guidelines for Diagnosis and Management of Hyperthyroidism and Other Causes of Thyrotoxicosis

Principles of exercise testing and interpretation

The relation between arterial function indices, such as pulse wave velocity and augmentation index with parameters derived from input impedance analysis, is still incompletely understood. Carotid pressure, central flow waveforms, and pulse wave velocity were noninvasively acquired in 2026 apparently healthy, middle-aged subjects (1052 women and 974 men) 35 to 55 years old at inclusion. Input and characteristic impedance, reflection coefficient, the ratio of backward-to-forward pressure amplitude (reflection magnitude), and augmentation index were derived. Pulse wave velocity increased by 15% (from 6.1 to 7.0 m/s) both in men and women. In qualitative terms, input impedance evolved from a pattern indicative of wave transmission and reflection to a pattern more compatible with a windkessel-like system. In women, a decrease in total arterial compliance led to an increased input impedance in the low frequency range, whereas few changes were observed in men. Characteristic impedance did not change with age in women and even decreased in men (P<0.001) and could not be identified as the primary determinant of central pulse pressure. Augmentation index increased with age, as was expected, and was systematically higher in women (P<0.001). Reflection coefficient and reflection magnitude increased with age (P<0.001) without gender differences. We conclude that, in healthy middle-aged subjects, the age-related increase in arterial stiffness (pulse wave velocity) is not fully paralleled by an increase in arterial impedance, suggesting a role for age-dependent modulation of aortic cross-sectional area. Wave reflection increases with age and is not higher in women than in men.

Noninvasive (input) impedance, pulse wave velocity, and wave reflection in healthy middle-aged men and women. Editorial Commentary

This study was undertaken to assess the value of sublingual nitroglycerin administration during u as a simple practical test for the diagnosis o P right tilt vasovagal syncope. To this purpose, 235 patients with syncope of unknown origin and no evidence of organic heart disease (110 men, mean age 52 f 20 years) and 35 asymptomatic control subjects underwent head-up tilt testing with nitroglycerin challenge. Patients and subjects were tilted at 60” for 45 + 20 minutes; the initial 45 minutes were without medication and the final 20 minutes after 300 pg of sublingual nitroglycerin. During the drug-free phase of the test, 59 patients (25%) and no controls had a positive response. After drug administration, a positive response (syncope in associa-

Value of Head-Up Tilt Testing Potentiated With Sublingual Nitro lycerm to Assess the Origin of Unexp ained 1 Syncope

A dedicated nonlinear oscillator model able to reproduce the pulse shape, refractory time, and phase sensitivity of the action potential of a natural pacemaker of the heart is developed. The phase space of the oscillator contains a stable node, a hyperbolic saddle, and an unstable focus. The model reproduces several phenomena well known in cardiology, such as certain properties of the sinus rhythm and heart block. In particular, the model reproduces the decrease of heart rate variability with an increase in sympathetic activity. A sinus pause occurs in the model due to a single, well-timed, external pulse just as it occurs in the heart, for example due to a single supraventricular ectopy. Several ways by which the oscillations cease in the system are obtained (models of the asystole). The model simulates properly the way vagal activity modulates the heart rate and reproduces the vagal paradox. Two such oscillators, coupled unidirectionally and asymmetrically, allow us to reproduce the properties of heart rate variability obtained from patients with different kinds of heart block including sino-atrial blocks of different degree and a complete AV block (third degree). Finally, we demonstrate the possibility of introducing into the model a spatial dimension that creates exciting possibilities of simulating in the future the SA the AV nodes and the atrium including their true anatomical structure.

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Nonlinear oscillator model reproducing various phenomena in the dynamics of the conduction system of the heart.

Background: The impact of subclinical hyperthyroidism (sHT) on the cardiovascular system still needs to be elucidated. The aim of the study was to prospectively assess blood pressure (BP), variability in heart rate, and the prevalence of arrhythmias in patients with sHT, both before and after they are restored to the euthyroid state. Methods: The study group consisted of 44 normotensive patients (37 women, 7 men), aged 22–65 years (mean±SD: 45.9±11.0) with sHT. Enrolled patients were drawn from 1080 patients referred to our department for treatment of hyperthyroidism. Study patients were treated with radioiodine treatment to restore the euthyroid state. Ambulatory BP monitoring and Holter electrocardiography were performed (i) when sHT was diagnosed and (ii) at least 6 months after they became euthyroid. Results: sHT in comparison to the euthyroid state was associated with higher (109.3±7.1 vs. 107.1±7.7 mmHg) nocturnal systolic mean BP (p=0.035) and BP load (14.8 vs. 10.2%, p=0.033), mean diastolic BP (6...

The Influence of Subclinical Hyperthyroidism on Blood Pressure, Heart Rate Variability, and Prevalence of Arrhythmias

BACKGROUND: Arterial hypertension might be caused by hemodynamic disturbances such as fluid retention, increased vascular resistance, and hyperdynamic function of the heart. The aim of this study was to estimate the effectiveness of antihypertensive therapy based on hemodynamic assessment by impedance cardiography in a randomized, prospective, controlled trial. MATERIAL AND METHODS: This study involved 128 patients (average age: 42.9 ± 11.1 years) with arterial hypertension, randomized into groups: (1) empiric, and (2) hemodynamic, in which treatment choice considered impedance cardiography results. Evaluation of treatment effects was performed after 12 weeks and included office blood pressure measurement and ambulatory blood pressure monitoring. RESULTS: All final blood pressure values were lower in the hemodynamic group, significantly for office systolic blood pressure (empiric vs. hemodynamic: 136.1 vs. 131.6 mmHg; p=0.036) and diastolic blood pressure (87.0 vs. 83.7 mmHg; p=0.013), as well as night-time systolic blood pressure (121.3 vs. 117.2 mmHg; p=0.023) and diastolic blood pressure (71.9 vs. 68.4 mmHg; p=0.007). Therapy based on impedance cardiography significantly increased the reduction in office systolic blood pressure (11.0 vs. 17.3 mmHg; p=0.008) and diastolic blood pressure (7.7 vs. 12.2 mmHg; p=0.0008); as well as 24-h mean systolic blood pressure (9.8 vs. 14.2 mmHg; p=0.026), daytime systolic blood pressure (10.5 vs. 14.8 mmHg; p=0.040), and night-time systolic blood pressure (7.7 vs. 12.2 mmHg; p=0.032). CONCLUSIONS: Antihypertensive treatment based on impedance cardiography can significantly increase blood pressure reduction in hypertensive patients.

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A "patient-tailored" treatment of hypertension with use of impedance cardiography: a randomized, prospective and controlled trial.

GrzegorzKaminski*,DariuszMichalkiewicz†,KarolMakowski†,ZbigniewPodgajny*,NorbertSzalus‡,MarekRuchala§,EwelinaSzczepanek§andGrzegorzGielerak†*DepartmentsofEndocrinologyandIsotopeTherapy,†InternalMedicineandCardiology,‡NuclearMedicine,MilitaryInstituteofMedicine,Warsawand§DepartmentofEndocrinology,MetabolismandInternalMedicine,PoznanUniversityofMedicalSciences,Poznan,PolandSummaryObjectivesClinical signiﬁcance of, and the need for, treatment insubclinical hyperthyroidism (sHT) is still a matter of debate. Theaim of the study was to assess the impact of sHT on echocardio-graphic parameters.Design Patients with endogenous sHT of nonautoimmune originunderwent full echocardiographic assessment at diagnosis and afterrestoring euthyroidism with radioiodine treatment.Patients Studied group consisted of 44 patients (37 women, 7men), aged 22–65 years (mean 45AE9±11 AE0).Measurements Full echocardiographic assessment included esti-mation of cardiac chamber diameters and volume as well as cardiaccontractility, according to the guidelines of the American Society ofEchocardiography. Left ventricular mass was calculated accordingto Penn’s convention. For estimation of left ventricle diastolicfunction, the following echocardiographic parameters wereobtained: maximal early ﬁlling wave velocity (E), maximal late ﬁll-ing wave velocity (A), E/A ratio, isovolumetric relaxation time andearly ﬁlling wave deceleration time.Results In the studied group, phase of sHT was associated withincreased volume of heart chambers, increased diameter of ascend-ing aorta, increased left ventricle mass and disturbed left ventriclerelaxation (P <0AE05). The systolic function of the left ventricle wasunaffected; however, the ejection time was shortened. The changeswere reversible with restoring biochemical euthyroidism(P <0AE05). Moreover, a signiﬁcant correlation between some ofthe parameters and thyroid hormones concentration was demon-strated.Conclusions sHT was associated with signiﬁcant changes inechocardiographic parameters, which may contribute to increasedcardiovascular risk in these patients. The alterations were reversiblewith restoring biochemical euthyroidism, what supports the neces-sity of treatment introduction in sHT.(Received 27 August 2010; returned for revision 14 October 2010;ﬁnally revised 7 December 2010; accepted 13 December 2010)IntroductionSubclinical hyperthyroidism (sHT) is a condition, which affects0 6–16% of the population and is characterized by a decreased orundetectable TSH level and normal concentration of free thyroidhormones.

Prospective echocardiographic evaluation of patients with endogenous subclinical hyperthyroidism and after restoring euthyroidism

Abdominal obesity (AO) is strongly associated with increased cardiovascular risk in hypertensives. Visceral adipose tissue has an important part in water retention, the sympathetic nervous system and renin-angiotensin-aldosterone system activation, which may influence central and systemic hemodynamics. The aim of this study was to estimate the relationship between AO and the hemodynamic profile of patients with arterial hypertension (AH). The clinical evaluation of 144 hypertensives included the following: (1) echocardiographic assessment of the left ventricular ejection fraction (LVEF), the global longitudinal systolic strain (GLSS) and diastolic function (E/A-phase ratio of mitral flow early (E) and late (A) and E/e'-ratio of early mitral flow and mitral septal annulus early diastolic velocity (e')); (2) the applanation tonometry including the central pulse pressure (CPP) and augmentation index (AI); and (3) the impedance cardiography, acceleration index (ACI), velocity index (VI), systemic vascular resistance index (SVRI) and total artery compliance (TAC). Obese hypertensives in comparison with non-obese ones were characterized with the following values: (1) lower echocardiographic (GLSS: -17.2±2.5% vs. -19.0±2.8%, P=0.0002) and impedance indices of left ventricular performance (VI: 44.8±12.4 vs. 51.6±14.2 × 1000*Ω* s(-1), P=0.006; ACI: 66.7±27.8 vs. 79.1±31.2 100*Ω* s(-)(2), P=0.003) and (2) worse diastolic function (e': 9.08±2.69 vs. 10.39±2.34 cm*s(-1), P=0.003; E/e': 7.54±1.81 vs. 6.74±1.40, P=0.007; E/A: 1.02±0.34 vs. 1.15±0.33, P=0.008). No relevant differences for gender, age, blood pressure, heart rate, LVEF, SVRI, TAC, CPP and AI were identified. AH and AO have overlapping effects on cardiovascular hemodynamics. At the early asymptomatic stage, this overlap is exhibited in the impaired cardiac function.

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Grzegorz Gielerak

Papers

Nonlinear oscillator model reproducing various phenomena in the dynamics of the conduction system of the heart.

The Influence of Subclinical Hyperthyroidism on Blood Pressure, Heart Rate Variability, and Prevalence of Arrhythmias

A "patient-tailored" treatment of hypertension with use of impedance cardiography: a randomized, prospective and controlled trial.

Prospective echocardiographic evaluation of patients with endogenous subclinical hyperthyroidism and after restoring euthyroidism

Abdominal obesity and hypertension: a double burden to the heart.