Amyloidosis - Amyloidosis - 339 · amyloidosis

Dr. Jan Griffin is a cardiologist at New York-Presbyterian/Columbia University Irving Medical Center in New York, NY. She graduated from the Royal College of Surgeons of Ireland with a medical degree. In this video Dr. Griffin discusses ATTR Amyloidosis: Current and Emerging Management Strategies.

Link to Abstract-
https://www.jacc.org/doi/10.1016/j.jaccao.2021.05.004

Abstract-
Because of noninvasive imaging and increased awareness, transthyretin cardiac amyloidosis (ATTR-CA) is becoming more common. Because pathogenic alleles do not have complete clinical penetrance, there is a substantial population of asymptomatic transthyretin variant carriers. More research is needed into screening techniques, monitoring, and therapy of subclinical ATTR-CA. The development of effective medicines based on a scientific understanding of ATTR-CA pathogenesis is perhaps the most significant translational success. These include recently established transthyretin protein stabilization and transthyretin production suppression methods. Data on neurohormonal blocking in ATTR-CA is scarce, with medical treatment focusing primarily on fluid management. Atrial fibrillation is a frequent condition that necessitates anticoagulation due to the risk of thrombus formation. Although conduction disorders and ventricular arrhythmias are common, little is known about the best ways to treat them. Finally, because aortic stenosis and ATTR-CA are usually seen together, transcatheter valve replacement is the chosen treatment option.
Highlights

• ATTR-CA is becoming more well-known as a result of increased awareness and the development of noninvasive diagnostic approaches.

• Clinical penetrance of harmful alleles is incomplete, with inadequate data for asymptomatic carriers' screening or care.

• Biological understanding of ATTR-CA pathophysiology has led to effective TTR stabilizers and silencers as targeted therapeutics.

• Future treatments could involve CRISPR, amyloid extraction/degradation, and amyloid seeding inhibition.

Introduction

Over the last decade, the field of transthyretin cardiac amyloidosis (ATTR-CA) has undergone a transformation, with an increasing recognition that many ATTR-CA patients were previously undiagnosed and instead assumed to have hypertension, heart failure with preserved ejection fraction (HFpEF), or hypertrophic cardiomyopathy (1). Delays in diagnosis were almost prevalent, and they still exist today, sadly (2). However, with increased awareness of clinical clues and the ability to diagnose ATTR-CA without a biopsy (3), reports have shown ATTR-CA in patients hospitalized with HFpEF (13%) (4), patients with severe aortic stenosis undergoing transcatheter aortic valve replacement (TAVR) (16%) (5), and up to 40% of high-risk populations, such as Afro-Caribbeans with heart failure and increased ventricular wall thickness undergoing TAVR (6). As a result, every cardiologist has come across patients with ATTR-CA, whether they are aware of it or not. Despite the exponential increase in the use of cardiac bone scintigraphy and multisocietal guidelines supporting nonbiopsy diagnosis (7,8), there are certain major traps to avoid. Failure to check for monoclonal proteins or an over-reliance on planar imaging are two examples (9). The development of effective medicines based on a biological understanding of the underlying pathophysiology has been the most significant "translational victory" (10). These treatments have a significant impact on the quality and quantity of life for those who are afflicted. This article focuses on the treatment of ATTR-CA patients and the evolving therapy landscape (Central Illustration).

Dr. Jan Griffin is a cardiologist at New York-Presbyterian/Columbia University Irving Medical Center in New York, NY. She graduated from the Royal College of Surgeons of Ireland with a medical degree. In this video Dr. Griffin discusses ATTR Amyloidosis: Current and Emerging Management Strategies.

Link to Abstract-
https://www.jacc.org/doi/10.1016/j.jaccao.2021.05.004

Abstract-
Because of noninvasive imaging and increased awareness, transthyretin cardiac amyloidosis (ATTR-CA) is becoming more common. Because pathogenic alleles do not have complete clinical penetrance, there is a substantial population of asymptomatic transthyretin variant carriers. More research is needed into screening techniques, monitoring, and therapy of subclinical ATTR-CA. The development of effective medicines based on a scientific understanding of ATTR-CA pathogenesis is perhaps the most significant translational success. These include recently established transthyretin protein stabilization and transthyretin production suppression methods. Data on neurohormonal blocking in ATTR-CA is scarce, with medical treatment focusing primarily on fluid management. Atrial fibrillation is a frequent condition that necessitates anticoagulation due to the risk of thrombus formation. Although conduction disorders and ventricular arrhythmias are common, little is known about the best ways to treat them. Finally, because aortic stenosis and ATTR-CA are usually seen together, transcatheter valve replacement is the chosen treatment option.
Highlights

• ATTR-CA is becoming more well-known as a result of increased awareness and the development of noninvasive diagnostic approaches.

• Clinical penetrance of harmful alleles is incomplete, with inadequate data for asymptomatic carriers' screening or care.

• Biological understanding of ATTR-CA pathophysiology has led to effective TTR stabilizers and silencers as targeted therapeutics.

• Future treatments could involve CRISPR, amyloid extraction/degradation, and amyloid seeding inhibition.

Introduction

Over the last decade, the field of transthyretin cardiac amyloidosis (ATTR-CA) has undergone a transformation, with an increasing recognition that many ATTR-CA patients were previously undiagnosed and instead assumed to have hypertension, heart failure with preserved ejection fraction (HFpEF), or hypertrophic cardiomyopathy (1). Delays in diagnosis were almost prevalent, and they still exist today, sadly (2). However, with increased awareness of clinical clues and the ability to diagnose ATTR-CA without a biopsy (3), reports have shown ATTR-CA in patients hospitalized with HFpEF (13%) (4), patients with severe aortic stenosis undergoing transcatheter aortic valve replacement (TAVR) (16%) (5), and up to 40% of high-risk populations, such as Afro-Caribbeans with heart failure and increased ventricular wall thickness undergoing TAVR (6). As a result, every cardiologist has come across patients with ATTR-CA, whether they are aware of it or not. Despite the exponential increase in the use of cardiac bone scintigraphy and multisocietal guidelines supporting nonbiopsy diagnosis (7,8), there are certain major traps to avoid. Failure to check for monoclonal proteins or an over-reliance on planar imaging are two examples (9). The development of effective medicines based on a biological understanding of the underlying pathophysiology has been the most significant "translational victory" (10). These treatments have a significant impact on the quality and quantity of life for those who are afflicted. This article focuses on the treatment of ATTR-CA patients and the evolving therapy landscape (Central Illustration).

Dr. Oscar M. Westin is a PHd student and a medical doctor at the University Hospital of Copenhagen's Heart Center, Rigshospitalet. In this video Dr. Westin speaks on the Two Decades of Cardiac Amyloidosis: A Danish Nationwide Study.


Link to Abstract-
https://www.jacc.org/doi/10.1016/j.jaccao.2021.05.004

Abstract-

Cardiac amyloidosis (CA) is linked to a bad prognosis. According to screening studies, CA is often ignored, especially in the elderly. Recent therapy improvements have drawn attention to the condition, although data on CA epidemiology across time is scarce.

Objectives

The goal of this study was to describe all CA patients in Denmark from 1998 to 2017, as well as to look at changes in patient characteristics over time.

Methods

In Danish nationwide registries, all patients with any kind of amyloidosis diagnosed between 1998 and 2017, as well as their comorbidities and medication, were identified. Any diagnosis code for amyloidosis paired with a diagnosis code for heart failure, cardiomyopathy, or atrial fibrillation, or a procedural code for pacemaker installation, regardless of order, was classified as CA. The index date was established as the date on which those criteria were met. By index date, patients were separated into 5-year segments. We also included control subjects (1:4 ratio) from the general population as a comparison.

Results

619 patients met the CA requirements. The median age at baseline grew from 67.4 years (interquartile range [IQR]: 53.9-75.2 years) in 1998-2002 to 72.3 years in 2013-2017. (IQR: 66.0-79.3 years). Male patients grew from 62.1 percent to 66.2 percent of all patients. In the Danish population aged 65 years, the incidence of CA increased from 0.88 to 3.56 per 100,000 person-years, whereas 2-year mortality reduced from 82.6 percent (IQR: 69.9 percent -90.5 percent) to 50.2 percent (IQR: 43.1 percent -56.9 percent ). CA patients had a considerably greater mortality rate than control participants (log-rank test: P 0.0001).

Conclusions

On a nationwide scale, CA, as defined in this study, was becoming more prevalent. The rising number of male patients and median age indicate that wild-type transthyretin amyloidosis is to blame. The fact that earlier, less advanced illnesses are being recognized more often could explain the lower fatality rate.

Dr. Oscar M. Westin is a PHd student and a medical doctor at the University Hospital of Copenhagen's Heart Center, Rigshospitalet. In this video Dr. Westin speaks on the Two Decades of Cardiac Amyloidosis: A Danish Nationwide Study.


Link to Abstract-
https://www.jacc.org/doi/10.1016/j.jaccao.2021.05.004

Abstract-

Cardiac amyloidosis (CA) is linked to a bad prognosis. According to screening studies, CA is often ignored, especially in the elderly. Recent therapy improvements have drawn attention to the condition, although data on CA epidemiology across time is scarce.

Objectives

The goal of this study was to describe all CA patients in Denmark from 1998 to 2017, as well as to look at changes in patient characteristics over time.

Methods

In Danish nationwide registries, all patients with any kind of amyloidosis diagnosed between 1998 and 2017, as well as their comorbidities and medication, were identified. Any diagnosis code for amyloidosis paired with a diagnosis code for heart failure, cardiomyopathy, or atrial fibrillation, or a procedural code for pacemaker installation, regardless of order, was classified as CA. The index date was established as the date on which those criteria were met. By index date, patients were separated into 5-year segments. We also included control subjects (1:4 ratio) from the general population as a comparison.

Results

619 patients met the CA requirements. The median age at baseline grew from 67.4 years (interquartile range [IQR]: 53.9-75.2 years) in 1998-2002 to 72.3 years in 2013-2017. (IQR: 66.0-79.3 years). Male patients grew from 62.1 percent to 66.2 percent of all patients. In the Danish population aged 65 years, the incidence of CA increased from 0.88 to 3.56 per 100,000 person-years, whereas 2-year mortality reduced from 82.6 percent (IQR: 69.9 percent -90.5 percent) to 50.2 percent (IQR: 43.1 percent -56.9 percent ). CA patients had a considerably greater mortality rate than control participants (log-rank test: P 0.0001).

Conclusions

On a nationwide scale, CA, as defined in this study, was becoming more prevalent. The rising number of male patients and median age indicate that wild-type transthyretin amyloidosis is to blame. The fact that earlier, less advanced illnesses are being recognized more often could explain the lower fatality rate.

We discuss transthyretin (aTTR) cardiac amyloidosis, symptoms, appropriate diagnostic testing and different treatment options available. Dr. Matt Maurer from NewYork-Presbyterian Hospital/Columbia University shares his expertise with us.

Listen, Like, Subscribe, and give us a rating!

Management of light chain or AL amyloidosis has changed with major advances in recent years. Dr. Ronald Witteles is a Stanford Cardiologist with particular expertise in the treatment of cardiac amyloidosis and shares his expertise with us. He serves as Co-Director of the Stanford Amyloid Center, one of the world's leading amyloid centers.

Listen, Like, Subscribe, and give us a rating!