Magnitude and time course of urinary iodine excretion in patients after amiodarone therapy.

BACKGROUND: Amiodarone is a source of iodine excess that may persist in the body for long time after its withdrawal. The aim of the present analysis was to evaluate the magnitude and long-term time course of 24-h urinary iodine (UI) excretion in patients on antiarrhythmic therapy with amiodarone. METHODS: 24-h UI excretion and thyroid function were evaluated in 67 patients on amiodarone therapy. All patients were clinically and biochemically euthyroid before starting treatment and were followed-up by 6-month measurements of 24-h UI excretion and plasma thyroid hormones levels. RESULTS: Upon amiodarone withdrawal, normal range of UI was achieved after a mean time of 15.2±7.7 months. Since amiodarone initiation, 20 patients developed thyroid dysfunction. No differences were observed in terms of treatment length or median UI levels between patients remaining euthyroid and those developing thyroid dysfunction: median UI in the euthyroid group was 8094 µg/24 h (Interquartile Range [IQR]: 4082-10766) vs. 10851 µg/24 h (IQR: 8529-12804) in the thyroid dysfunction group at 6 months (P=0.176) and 8651 µg/24 h (IQR: 6924-11574) vs. 8551 µg/24 h (IQR: 4916-13580) at one year from amiodarone initiation (P=0.886). The occurrence of thyroid dysfunction was equally distributed among patients taking amiodarone for more than one year versus those under treatment for less than one year. CONCLUSIONS: These results confirm the long-lasting total-body iodine stores and consequent excretion in patients after amiodarone withdrawal. These long-lasting iodine stores might be taken into special account in patients necessitating therapy with radioactive iodine and for long-term monitoring of thyroid function after amiodarone discontinuation.

Current experimental and early investigational agents for cardiac fibrosis: where are we at?

INTRODUCTION: Myocardial fibrosis (MF) is induced by factors activating pro-fibrotic pathways such as acute and prolonged inflammation, myocardial ischemic events, hypertension, aging process, and genetically-linked cardiomyopathies. Dynamics and characteristics of myocardial fibrosis development are very different. The broad range of myocardial fibrosis presentations suggests the presence of multiple potential targets. AREA COVERED: Heart failure treatment involves medications primarily aimed at counteracting neurohormonal activation. While these drugs have demonstrated efficacy against MF, not all specifically target inflammation or fibrosis progression with some exceptions such as RAAS inhibitors. Consequently, new therapies are being developed to address this issue. This article is aimed to describe anti-fibrotic drugs currently employed in clinical practice and emerging agents that target specific pathways, supported by evidence from both preclinical and clinical studies. EXPERT OPINION: Despite various preclinical findings suggesting the potential utility of new drugs and molecules for treating cardiac fibrosis in animal models, there is a notable scarcity of clinical trials investigating these effects. However, the pathology of damage and repair in the heart muscle involves a complex network of interconnected inflammatory pathways and various types of immune cells. Our comprehension of the positive and negative roles played by specific immune cells and cytokines is an emerging area of research.

Clinical and functional effects of beta-blocker therapy discontinuation in patients with biventricular heart failure.

BACKGROUND: Nearly two-thirds of patients with heart failure with reduced ejection fraction (HFrEF) have right ventricular dysfunction, previously identified as an independent predictor of reduced functional capacity and poor prognosis. Beta-blocker therapy (ß-BT) reduces mortality and hospitalizations in patients with HFrEF and is approved as first-line therapy regardless of concomitant right ventricular function. However, the exact role of sympathetic nervous system activation in right ventricular dysfunction and the potential usefulness (or harmfulness) of ß-BT in these patients are still unclear. OBJECTIVES: The aim of the study is to evaluate the medium-term effect of ß-BT discontinuation on functional capacity and right ventricular remodelling based on cardiopulmonary exercise testing (CPET), echocardiography and serum biomarkers in patients with clinically stable biventricular dysfunction. METHODS: In this single-centre, open-label, prospective trial, 16 patients were enrolled using the following criteria: patients were clinically stable without signs of peripheral congestion; NYHA II-III while on optimal medical therapy (including ß-BT); LVEF 40% or less; echocardiographic criteria of right ventricular dysfunction. Patients were randomized 1 : 1 either to withdraw (group 0) or continue (group 1) ß-BT. In group 0, optimal heart rate was obtained with alternative rate-control drugs. Echo and serum biomarkers were performed at baseline, after 3 and 6 months; CPET was performed at baseline and 6 months. Mann--Whitney U test was adopted to determine the relationships between ß-BT discontinuation and effects on right ventricular dysfunction. RESULTS: At 6 months' follow up, S' DTI improved (ΔS': 1.01 vs. -0.92 cm/s; P = 0.03), while estimated PAPs (ΔPAPs: 0.8 vs. -7.5 mmHg; P = 0.04) and echo left ventricular-remodelling (ΔEDVi: 19.55 vs. -0.96 ml/mq; P = 0.03) worsened in group 0. In absolute terms, the only variables significantly affected by ß-BT withdrawal were left ventricular EDV and ESV, appearing worse in group 0 (mean EDVi 115 vs. 84 ml/mq; mean ESVi 79 vs. 53.9 ml/mq, P = 0.03). No significant changes in terms of functional capacity were observed after ß-BT withdrawal. CONCLUSION: In HFrEF patients with concomitant right ventricular dysfunction, ß-BT discontinuation did not produce any beneficial effects. In addition, despite maintenance of optimal heart rate control, ß-BT discontinuation induced worsening of left ventricular remodelling. Our study corroborates the hypothesis that improvement in left ventricular function may likewise be a major determinant for improvement in right ventricular function, reducing pulmonary wedge pressure and right ventricular afterload, with only a marginal action of its negative inotropic effect. In conclusion, ß-BT appears beneficial also in heart failure patients with biventricular dysfunction.

The origin of the popular iconic heart symbol: fiction or facts?

The heart is generally perceived as the core of emotion, affection, and love. Its universally accepted iconic representation is everywhere these sentiments have to be depicted. However, the question is: where does the popular heart shape comes from? In fact, it is difficult to relate this symbol to the real heart shape. With possible early examples or direct predecessors in the 13th to 14th century, the familiar symbol of the heart representing love developed in the 15th century, and became popular in Europe during the 16th. While performing several coronary total occlusion recanalization procedures, it has become excitingly evident that, during contemporaneous dual injections of both right and left coronary arteries, the iconic shadow of the heart can be effectively observed. The possibility that the evidence of this cardiac shape could already be visible to the eyes of people living at the time of the first iconic appearances of the heart image is difficult to surmise. How could our ancestors connect the iconic form to the real heart shape? In the present article, we discuss how this iconic shape could have been derived from anatomical observations made in the ancient world.

The Concept of "Heart Failure with Preserved Ejection Fraction": Time for a Critical Reappraisal.

Heart failure with preserved ejection fraction (HFpEF) is frequently observed in elderly physically deconditioned subjects, mainly women with hypertension, obesity, glucose intolerance/diabetes, atrial fibrillation, anaemia, coronary artery disease, chronic pulmonary disease, and chronic renal insufficiency. In practice, these conditions represent the majority of cardiac diseases we deal with in our daily clinical practice. For this reason, the HFpEF disease does not exist as a single entity and, as such, no specific unifying therapy could be found. New classification attempts still do not consider the multifaceted aspect of the HF syndrome and appear rather as an artefactual attempt to categorize a condition which is indeed not categorizable. The aim of the present article is to critically review the construction of the concept of the HFpEF syndrome and propose the return of a pathophysiological approach in the evaluation and treatment of patients. Considering the huge economic efforts employed up to date to run awfully expensive trials and research in this field, it is time to call action and redirect such resources towards more specific pathophysiological classifications and potential specific therapeutic targets.