A Machine Learning Model for the Systematic Identification of Wild-Type Transthyretin Cardiomyopathy

Huda, Ahsan; Shah, Sanjiv J.; Castaño, Adam; Niyogi, Anindita; Schumacher, Jennifer; Stewart, Michelle; Deo, Rahul C.

doi:10.1016/j.cardfail.2019.07.151

Cited by 6 publications

(4 citation statements)

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“…Expert consensus recommendations suggest that a diagnosis of ATTR-CM should be considered in patients with signs of heart failure and one or more of these red flags [7, 8, 11, 15, 17-19, 27, 28]. Research and predictive analytics are underway to create screening and diagnostic clinical decision support tools for ATTR-CM based on these red flags [2,11,[27][28][29]. These initiatives may improve the speed and accuracy of ATTR-CM diagnosis.…”

Section: Discussionmentioning

confidence: 99%

Real-World Characteristics of Patients with Wild-Type Transthyretin Amyloid Cardiomyopathy: An Analysis of Electronic Healthcare Records in the United States

Bhambri

Colavecchia

Bruno

et al. 2023

Am J Cardiovasc Drugs

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Background Tafamidis was approved for the treatment of hereditary and wild-type transthyretin amyloid cardiomyopathy (ATTRwt-CM) in May 2019, based on findings from the Tafamidis in Transthyretin Cardiomyopathy Clinical Trial (ATTR-ACT). Methods This retrospective cohort study evaluated the factors associated with tafamidis prescription after diagnosis of ATTRwt-CM in the real world. Between May 2019 and December 2020, 430 patients with 6 months' database activity were indexed from the de-identified US Optum electronic healthcare records at first diagnosis of ATTRwt-CM or prescription of tafamidis, then followed until last activity or death. Of these, 209 patients were prescribed tafamidis during follow-up, 167 (80%) within 1 month, 98% by 6 months, and 100% by 9 months. Median time from index to tafamidis prescription, calculated using the Kaplan-Meier method, was 5.8 months (95% confidence interval [CI] 2.4-not evaluable). Results Factors associated with tafamidis prescription in a multivariable Cox proportional hazards regression (hazard ratio [95% CI]) included age ≥ 65 years (2.1 [1.07-4.05]), male sex (1.6 [1.07-2.28]), having heart failure/cardiomyopathy (2.4 [1.54-3.82]), and having had technetium-99m pyrophosphate myocardial scintigraphy (1.7 [1.28-2.28]). Conclusions The clinical characteristics of patients with ATTRwt-CM who were prescribed tafamidis in the real world were broadly comparable with those who took part in ATTR-ACT. Further studies are needed to evaluate hereditary and ATTRwt-CM patient populations in the real world and assess the long-term outcomes associated with disease management pathways. Clinical Trials Registration ClinicalTrials.gov identifier: NCT01994889. Key Points430 patients with transthyretin amyloid cardiomyopathy were identified in the Optum electronic health record database; 49% (n = 209) were prescribed tafamidis (median time to prescription: 5.8 months).Real-world patients prescribed tafamidis were broadly similar to patients in the Tafamidis in Transthyretin Cardiomyopathy Clinical Trial (ATTR-ACT).We identified several factors associated with tafamidis prescription: older age, male sex, cardiac comorbidities, and technetium-99m pyrophosphate scintigraphy.

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Section: Discussionmentioning

confidence: 99%

Real-World Characteristics of Patients with Wild-Type Transthyretin Amyloid Cardiomyopathy: An Analysis of Electronic Healthcare Records in the United States

Bhambri

Colavecchia

Bruno

et al. 2023

Am J Cardiovasc Drugs

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“… 63 Moreover, work is ongoing on artificial intelligence and machine learning models using electronic health records and imaging technologies capable of identifying patients at risk of having ATTR-CM. 128 These models may eventually be used to increase the index of suspicion of ATTR-CM to support prompt diagnosis of the disease in the clinical practice setting. Finally, educational initiatives and research/decision support tools are in development for systematic adoption by health systems to help ensure that patients with rare diseases such as ATTR-CM are not overlooked.…”

Section: Discussionmentioning

confidence: 99%

Drug Discovery and Development in Rare Diseases: Taking a Closer Look at the Tafamidis Story

Burton¹,

Castaño²,

Bruno³

et al. 2021

DDDT

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Rare diseases are increasingly recognized as a global public health priority. Governments worldwide currently provide important incentives to stimulate the discovery and development of orphan drugs for the treatment of these conditions, but substantial scientific, clinical, and regulatory challenges remain. Tafamidis is a first-in-class, disease-modifying transthyretin (TTR) kinetic stabilizer that represents a major breakthrough in the treatment of transthyretin amyloidosis (ATTR amyloidosis). ATTR amyloidosis is a rare, progressive, and fatal systemic disorder caused by aggregation of misfolded TTR and extracellular deposition of amyloid fibrils in various tissues and organs, including the heart and nervous systems. In this review, we present the successful development of tafamidis spanning 3 decades, marked by meticulous laboratory research into disease mechanisms and natural history, and innovative clinical study design and implementation. These efforts established the safety and efficacy profile of tafamidis, leading to its regulatory approval, and enabled post-approval initiatives that further support patients with ATTR amyloidosis.

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“…It has been proposed that patients who have risk factors such as male gender, age ≥65 yrs, heart failure symptoms, symmetric left ventricular (LV) hypertrophy, and moderately depressed or HFpEF should undergo screening for amyloidosis [17]. Machine learning models have also been investigated and may provide novel insights into early diagnosis of ATTRwt patients [23]. ere are other clinical implications as well.…”

Section: Discussionmentioning

confidence: 99%

Senile Systemic Amyloidosis Presenting as Hematuria: A Rare Presentation and Review of Literature

Jayakrishnan

Kamran

Shah

et al. 2020

Case Reports in Medicine

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Introduction. Senile systemic amyloidosis is a multisystem disease where wild-type insoluble transthyretin (ATTRwt) protein gets deposited in the tissues leading to organ dysfunction. Methodology. We present the case of a patient who presented with hematuria and bladder involvement by ATTRwt amyloidosis who ultimately died of multiorgan failure. Results. The patient was an 82-year-old white male with a history of ischemic cardiomyopathy (ejection fraction (EF): 20–25%), chronic atrial fibrillation, chronic kidney disease (CKD), and carpal tunnel syndrome who presented with acute hematuria, urinary retention, and progressive fatigue. He underwent cystoscopy and bladder biopsy which was positive on congo-red stain diagnostic for amyloidosis. Echocardiogram demonstrated worsening of EF to 10–15% and concentric left ventricle hypertrophy. MRI was not performed due to underlying CKD. His condition deteriorated during the hospital stay, and he developed cardiogenic shock and progressive liver dysfunction. Infectious workup was negative. Meanwhile, the biochemical investigations (serum protein electrophoresis, immunofixation, and urine kappa/lambda chains) ruled out plasma cell dyscrasias. Mass spectrometry analysis of the bladder biopsy specimen confirmed wild-type transthyretin (ATTRwt) amyloidosis consistent with senile systemic amyloidosis. Due to patients’ extremely poor prognosis, his family wished to focus on patient’s comfort-oriented measures only, and patient passed away shortly thereafter. Conclusion. Senile systemic amyloidosis can rarely present in an atypical fashion such as hematuria. The treatment options are limited in this disease process. Novel therapies are in the early phases of development. Concern also exists that in patients with multiple comorbidities, this entity is under recognized until the more advanced stages.

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A Machine Learning Model for the Systematic Identification of Wild-Type Transthyretin Cardiomyopathy

Cited by 6 publications

References 0 publications

Real-World Characteristics of Patients with Wild-Type Transthyretin Amyloid Cardiomyopathy: An Analysis of Electronic Healthcare Records in the United States

Real-World Characteristics of Patients with Wild-Type Transthyretin Amyloid Cardiomyopathy: An Analysis of Electronic Healthcare Records in the United States

Drug Discovery and Development in Rare Diseases: Taking a Closer Look at the Tafamidis Story

Senile Systemic Amyloidosis Presenting as Hematuria: A Rare Presentation and Review of Literature

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