Screening for Transthyretin Amyloid Cardiomyopathy in Everyday Practice

Witteles, Ronald; Bokhari, Sabahat; Damy, Thibaud; Elliott, Perry; Falk, Rodney H.; Fine, Nowell M.; Господинова, Мариана; Obici, Laura; Rapezzi, Claudio; García‐Pavía, Pablo

doi:10.1016/j.jchf.2019.04.010

Cited by 210 publications

(346 citation statements)

References 40 publications

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“…[6][7][8]14 CTS is known as an early symptom in ATTRwt preceding cardiac involvement, and a history of bilateral CTS is a 'red flag' in ATTRwt-CM diagnosis. 15 The incidence of CTS was reported to range between 33% and 48% in patients with ATTR-CM. [6][7][8]14 If possible, the history of CTS was re-examined to prevent any case being overlooked; consequently, the frequency was slightly higher in this study than in previous reports.…”

Section: Discussionmentioning

confidence: 99%

Clinical characteristics and natural history of wild‐type transthyretin amyloid cardiomyopathy in Japan

et al. 2020

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Aims The focus on wild-type transthyretin amyloid cardiomyopathy (ATTRwt-CM) is increasing because of novel treatment options. There is currently no report on a large number of Japanese patients with ATTRwt-CM. The study aimed to examine the characteristics and prognosis of ATTRwt-CM in Japan. Methods and results Consecutive patients (78.5 ± 6.4 years old at diagnosis) with ATTRwt-CM diagnosed at Kumamoto University Hospital between December 2002 and December 2019 were retrospectively reviewed. Data, including demographic characteristics, co-morbidities, clinical manifestations at diagnosis, laboratory results, electrocardiographic and echocardiographic data, imaging and pathological findings, and treatment were obtained. Of 129 patients included in this study, 110 patients (85%) were male. The median period from initial symptom onset to diagnosis was 15.5 (2-75) months. Heart failure was the most common clinical manifestation leading to diagnosis (61%) and initial manifestations (49%). Of 106 patients, carpal tunnel syndrome was observed in 57 patients (54%), and the median period from initial symptom onset to diagnosis was 96 (48-120) months. Histopathological confirmation of transthyretin amyloid was achieved in 94 patients (73%), including 66 (51%) and 28 cases (22%) with endomyocardial and extracardiac biopsies. During the observation period (median 15.0 [inter-quartile range, 5.4-33.2] months after diagnosis), 34 patients (26%) died. Of these, 27 patients (79%) had cardiovascular deaths (heart failure, 25; sudden death, two). The median survival duration was 58.9 months and the 5 years' survival rate was 48%. According to a multivariate Cox hazard analysis, age [hazard ratio (HR), 1.14; 95% confidence interval (CI), 1.05-1.23, P = 0.002] and low serum sodium levels (HR, 0.89; 95% CI, 0.79-0.996; P = 0.04) contributed to all-cause mortality, and low serum sodium levels contributed to hospitalization for heart failure (HR, 0.86; 95% CI, 0.77-0.96; P = 0.005). Conclusions Clinical characteristics and prognosis of ATTRwt-CM patients in Japan were examined. Carpal tunnel syndrome can be considered an indication for diagnosis of ATTRwt-CM. Age and low serum sodium level were significant predictive factors of all survival outcomes. The clinical features of ATTRwt-CM should be recognized to provide appropriate treatment.

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Section: Discussionmentioning

confidence: 99%

Clinical characteristics and natural history of wild‐type transthyretin amyloid cardiomyopathy in Japan

et al. 2020

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“…25 However, most of these clinical signs should now be considered as 'red flags' of the disease and reduce diagnostic delays. 28…”

Section: Discussionmentioning

confidence: 99%

Gateway and journey of patients with cardiac amyloidosis

et al. 2020

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Aims Advances have been made over the last decade in the management of cardiac amyloidosis (CA), but a delayed diagnosis is still common. The aim of this study was to describe the journey to CA diagnosis from initial clinical and to analyse time to diagnosis. Methods and results Between January 2001 and May 2019, 270 consecutive patients with CA diagnosed at Toulouse University Hospital were retrospectively included in this cross-sectional study: 111 (41%) light chain amyloidosis, 122 (45%) wild-type transthyretin amyloidosis, and 37 (14%) hereditary transthyretin amyloidosis. CA onset occurred mostly with dyspnoea (50%) or systematic follow-up (10%). The cardiologist was the first line specialist in 68% of patients, followed by the nephrologist (9%) and neurologist (8%). Patients encountered a median (minimum-maximum) number of two (1-7) physician specialists and performed a median (minimum-maximum) number of three (1-8) tests before diagnosis. Median delay between symptom onset and CA diagnosis was 8 [IQR 5-14], 10 [IQR 3-34], and 18 [IQR 4-49] months, respectively, in light chain amyloidosis, wild-type transthyretin amyloidosis, and hereditary transthyretin amyloidosis subgroups (P = .060). Having performed electromyography or spirometry was associated with a longer delay in diagnosis in the overall population: odds ratio = 1.13; 95% confidence interval 1.02 to 1.24; and odds ratio = 1.13; 1.03 to 1.24, respectively, probably due to non-specific initial symptoms. Conclusions CA is a protean disease with various first line specialists causing a diagnostic wandering despite increasing medical community awareness. It requires a multidisciplinary specialist care networks to educate and manage symptoms and therapies.

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“…Red flags for transthyretin amyloidosis may include multisystem organ involvement, bilateral carpal tunnel syndrome, spinal stenosis, a discordance between the electrocardiogram (ECG) voltage and wall thickness seen on cardiac imaging, orthostatic hypotension, intolerance to standard heart failure medications such as angiotensinreceptor enzyme inhibitors (ACE inhibitors) and betablockers, paradoxical low flow/low gradient aortic stenosis, alternating diarrhea and constipation, and unexplained peripheral neuropathy ( Figure 2). 3,4 Imaging clues for cardiac involvement may include an apical sparing pattern on global longitudinal strain on echocardiography with an apical-to-basal strain ratio >2.1, diffuse subendocardial late gadolinium enhancement or increased extracellular volume on MRI, and increased uptake of the bone avid tracers technetium 99 m technetium pyrophosphate ( 99m Tc-PYP), 99m Tc 3,3-disphonphone-1,2-propanodicarboxylic acid ( 99m Tc-DPD), or 99m technetium hydroxymethylene diphosphate ( 99m Tc99-HMDP) on nuclear bone scintigraphy. 3,4 Neurologic clues may include carpal tunnel syndrome, progressive axonal polyneuropathy or dysautonomia.…”

Section: Integrating the History Physical And Test Results: Red Flamentioning

confidence: 99%

“…3,4 Imaging clues for cardiac involvement may include an apical sparing pattern on global longitudinal strain on echocardiography with an apical-to-basal strain ratio >2.1, diffuse subendocardial late gadolinium enhancement or increased extracellular volume on MRI, and increased uptake of the bone avid tracers technetium 99 m technetium pyrophosphate ( 99m Tc-PYP), 99m Tc 3,3-disphonphone-1,2-propanodicarboxylic acid ( 99m Tc-DPD), or 99m technetium hydroxymethylene diphosphate ( 99m Tc99-HMDP) on nuclear bone scintigraphy. 3,4 Neurologic clues may include carpal tunnel syndrome, progressive axonal polyneuropathy or dysautonomia. Amyloidosis should be included in the differential diagnosis of peripheral neuropathy associated with autonomic involvement, especially in patients without diabetes.…”

Section: Integrating the History Physical And Test Results: Red Flamentioning

confidence: 99%

<p>Diagnosis and Screening of Patients with Hereditary Transthyretin Amyloidosis (hATTR): Current Strategies and Guidelines</p>

Benson

Dasgupta

Rao

2020

TCRM

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The outlook for transthyretin amyloidosis (ATTR) is changing with the availability of new and emerging treatments. ATTR now appears to be more common than previously thought and is no longer viewed as an obscure diagnosis with a grim prognosis. Now more than ever, there is growing emphasis on the need for early diagnosis because the treatments appear to be most effective if started in earlier stages of the disease. Diagnosing ATTR is a challenge as it may initially present with nonspecific symptoms and it is often thought of as a diagnosis of exclusion. Increased awareness is imperative as new treatments offer hope and have the potential to change the disease trajectory. ATTR commonly presents with neurological and cardiac features. Transthyretin (TTR) is a protein produced in the liver which misfolds either due to genetic mutations or due to aging and results in deposition of amyloid fibrils in organs and tissues. Apart from the traditional imaging modalities, newer techniques including echocardiographic strain imaging, magnetic resonance imaging (MRI), and nuclear scintigraphy, as well as the increased availability of genetic testing are aiding in making a timely diagnosis. In this review, we present the current understanding of the ATTR disease process, diagnostic and surveillance approaches, newer treatment modalities, and the future directions.

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Screening for Transthyretin Amyloid Cardiomyopathy in Everyday Practice

Cited by 210 publications

References 40 publications

Clinical characteristics and natural history of wild‐type transthyretin amyloid cardiomyopathy in Japan

Clinical characteristics and natural history of wild‐type transthyretin amyloid cardiomyopathy in Japan

Gateway and journey of patients with cardiac amyloidosis

<p>Diagnosis and Screening of Patients with Hereditary Transthyretin Amyloidosis (hATTR): Current Strategies and Guidelines</p>

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