15
views
0
recommends
+1 Recommend
0 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      Cardiac Transthyretin-derived Amyloidosis: An Emerging Target in Heart Failure with Preserved Ejection Fraction?

      review-article

      Read this article at

      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          Heart failure with preserved ejection fraction (HFpEF) comprises half of the heart failure population. A specific, but underdiagnosed, cause for HFpEF is transthyretin-derived (ATTR) amyloidosis. This article reviews the clinical characteristics of cardiac ATTR amyloidosis. The clinical suspicion of cardiac ATTR amyloidosis is strong if pronounced left ventricular hypertrophy is present in the absence of hypertension. Scintigraphy with a diphosphonate tracer is a diagnostic tool for the early detection of cardiac ATTR amyloidosis with high sensitivity and specificity. First treatment options for ATTR amyloidosis recently emerged, and showed a reduction in morbidity and mortality, especially if treatment was started in the early stages of disease. In light of these results, screening for ATTR amyloidosis in the general HFpEF population with left ventricular hypertrophy might be useful.

          Related collections

          Most cited references12

          • Record: found
          • Abstract: found
          • Article: not found

          The pathophysiology of heart failure with preserved ejection fraction.

          Approximately half of all patients with heart failure have preserved ejection fraction (HFpEF) and, as life expectancies continue to increase in western societies, the prevalence of HFpEF will continue to grow. In contrast to heart failure with reduced ejection fraction (HFrEF), no treatment has been proven in pivotal clinical trials to be effective for HFpEF, largely because of the pathophysiological heterogeneity that exists within the broad spectrum of HFpEF. This syndrome was historically considered to be caused exclusively by left ventricular diastolic dysfunction, but research has identified several other contributory factors, including limitations in left ventricular systolic reserve, systemic and pulmonary vascular function, nitric oxide bioavailability, chronotropic reserve, right heart function, autonomic tone, left atrial function, and peripheral impairments. Multiple individual mechanisms frequently coexist within the same patient to cause symptomatic heart failure, but between patients with HFpEF the extent to which each component is operative can differ widely, confounding treatment approaches. This Review focuses on our current understanding of the pathophysiological mechanisms underlying HFpEF, and how they might be mechanistically related to typical risk factors for HFpEF, including ageing, obesity, and hypertension.
            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found
            Is Open Access

            Transthyretin Stabilization by AG10 in Symptomatic Transthyretin Amyloid Cardiomyopathy

            Transthyretin (TTR) amyloidosis is an underdiagnosed disease caused by destabilization of TTR due to pathogenic mutations or aging. Both pathogenic and protective mutations illuminate mechanisms of disease and potential interventions. AG10 is a selective, oral TTR stabilizer under development for transthyretin amyloidosis cardiomyopathy (ATTR-CM) that mimics a protective TTR mutation.
              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              Doxycycline plus tauroursodeoxycholic acid for transthyretin amyloidosis: a phase II study.

              We designed a phase II, open-label study to evaluate the efficacy, tolerability, safety, and pharmacokinetics of orally doxycycline (100 mg BID) and tauroursodeoxycholic acid (TUDCA) (250 mg three times/day) administered continuously for 12 months. Primary endpoint is response rate defined as nonprogression of the neuropathy and of the cardiomyopathy. Since July 2010, we enrolled 20 patients. Seventeen patients have hereditary ATTR, two patients have senile systemic amyloidosis, and one is a domino recipient. Seven patients completed 12-month treatment, 10 completed 6-month treatment, two discontinued because of poor tolerability, and one is lost at follow-up. No serious adverse events were registered. No clinical progression of cardiac involvement was observed. The neuropathy (Neuropathy Impairment Score in the Lower Limbs [NIS-LL] and Kumamoto score) remained substantially stable over 1 year. These preliminary data indicate that the combination of Doxy-TUDCA stabilizes the disease for at least 1 year in the majority of patients with an acceptable toxicity profile.
                Bookmark

                Author and article information

                Journal
                Card Fail Rev
                Card Fail Rev
                CFR
                Cardiac Failure Review
                Radcliffe Cardiology
                2057-7540
                2057-7559
                07 August 2020
                March 2020
                : 6
                : e21
                Affiliations
                [1. ] Department of Cardiology, University of Groningen, University Medical Center Groningen Groningen, the Netherlands
                [2. ] Department of Internal Medicine, Division of Vascular Medicine, University of Groningen, University Medical Center Groningen Groningen, the Netherlands
                [3. ] Amyloidosis Centre of Expertise, University of Groningen, University Medical Center Groningen Groningen, the Netherlands
                Author notes

                Disclosure: HLAN received consultancy fees from Pfizer and Alnylam. PvdM received consultancy fees and/or research grants from Servier, Ionis, Astra Zeneca, Pfizer, Vifor Pharma and Novartis. All other authors have no conflicts of interest to declare.

                Correspondence: Peter van der Meer, Department of Cardiology, University Medical Center Groningen, PO Box 30001, 9700RB Groningen, the Netherlands. E: p.van.der.meer@ 123456umcg.nl
                Article
                10.15420/cfr.2019.16
                7479537
                37a3e984-f9a1-4e2d-99f9-08ebee603a6e
                Copyright © 2020, Radcliffe Cardiology

                This work is open access under the CC-BY-NC 4.0 License which allows users to copy, redistribute and make derivative works for non-commercial purposes, provided the original work is cited correctly.

                History
                : 13 November 2019
                : 29 January 2020
                Page count
                Pages: 4
                Categories
                Cardiac Amyloidosis

                heart failure with preserved ejection fraction,cardiac transthyretin-derived amyloidosis,scintigraphy,tafamidis,cardiomyopathy,treatment

                Comments

                Comment on this article