Imaging of the Mitral Valve.

Echocardiographic imaging is the foundation for the evaluation of mitral valve dysfunction. Both transthoracic and transesophageal echocardiography provide insight into the anatomy, pathology, and classification mitral valve dysfunction. Echocardiography also provides a multi-parametric approach with semi-quantitative and quantitative parameters to assess the severity of mitral regurgitation and mitral stenosis. Transesophageal imaging is essential in the assessment of patients considered for surgical or transcatheter interventional strategies to treat mitral valve dysfunction. Cardiac computed tomography (CT) and cardiac MRI are useful adjunctive imaging techniques in mitral valve disease with CT providing detailed procedural specificity and MRI providing detailed ventricular and regurgitant flow analysis.

Functional Mitral Regurgitation: Patient Selection and Optimization.

Functional mitral regurgitation appears commonly among all heart failure phenotypes and can affect symptom burden and degree of maladaptive remodeling. Transcatheter mitral valve edge-to-edge repair therapies recently became an important part of the routine heart failure armamentarium for carefully selected and medically optimized candidates. Patient selection is considering heart failure staging, relevant comorbidities, as well as anatomic criteria. Indications and device platforms are currently expanding.

Comparative Outcomes of a Transthyretin Amyloid Cardiomyopathy Cohort Versus Patients With Heart Failure With Preserved Ejection Fraction Enrolled in the TOPCAT Trial.

Background Transthyretin cardiac amyloidosis (ATTR-CM), found in 6% to 15% of cohorts with heart failure with preserved ejection fraction, has long been considered a rare disease with poor prognosis. New treatments have made it one of the few directly treatable causes of heart failure. This study sought to determine whether patients with ATTR-CM, particularly those treated with tafamidis, have comparable survival to an unselected cohort with heart failure with preserved ejection fraction. Methods and Results We compared the clinical characteristics and outcomes between a single-center cohort of patients with ATTR-CM (n=114) and patients with heart failure with preserved ejection fraction enrolled in the TOPCAT (Treatment of Preserved Cardiac Function Heart Failure With an Aldosterone Antagonist) trial (n=1761, excluding Russia and Georgia). The primary outcome was a composite of all-cause death, heart failure hospitalization, myocardial infarction, and stroke. Subgroup analysis of patients with ATTR-CM treated with tafamidis was also performed. Patients with ATTR-CM had higher rates of the primary composite outcome compared with patients enrolled in the TOPCAT trial (hazard ratio [HR], 1.44 [95% CI, 1.09-1.91]; P=0.01), with similar rates of all-cause death (HR, 1.43 [95% CI, 0.99-2.06]; P=0.06) but higher rates of heart failure hospitalizations (HR, 1.62 [95% CI, 1.15-2.28]; P<0.01). Compared with patients enrolled in TOPCAT, patients with ATTR-CM treated with tafamidis had similar rates of the primary composite outcome (HR, 1.30 [95% CI, 0.86-1.96]; P=0.21) and all-cause death (HR, 1.10 [95% CI, 0.57-2.14]; P=0.78) but higher rates of heart failure hospitalizations (HR, 1.96 [95% CI, 1.27-3.02]; P<0.01). Conclusions Patients with ATTR-CM treated with tafamidis have similar rates of all-cause death compared with patients with heart failure with preserved ejection fraction, with higher rates of heart failure hospitalizations.

Evolving epidemiology of transthyretin amyloid cardiomyopathy due to increased recognition in women.

BACKGROUND: Transthyretin amyloid cardiomyopathy (ATTR-CM), particularly wild type (wtATTR-CM), is thought to mainly affect men. Non-invasive diagnosis and approved therapeutics have been associated with increased disease recognition. We investigated the trajectory of ATTR-CM diagnosis in women. METHODS: This observational study utilized data collected on 140 consecutive ATTR-CM patients diagnosed between 2005 and 2022 who are followed at the Oregon Health and Science University Amyloidosis Clinic. Subgroup analysis was performed on patients with wtATTR-CM which included 113 subjects (80.1%). The proportion of women among patients diagnosed with ATTR-CM prior to 2019 was compared with that of those diagnosed 2019-2022 (2019 was the year of tafamidis approval by the FDA). The clinical characteristics of male and female ATTR-CM patients were compared as well. RESULTS: Of the 140 ATTR-CM patients, 16 (11.4%) were women (age 77 ± 9 years) and 124 (88.6%) were men (age 76 ± 9 years). There was an increase in the rate of women diagnosed with ATTR-CM from pre 2019 to 2019-2022 in the overall cohort (4/68 [5.9%] vs 12/72 [16.7%]) and wild type subgroup (0/51 [0%] vs 7/62 [11.3%]). There were several differences in baseline clinical characteristics between women and men in this cohort, yet all women had a clear clinical phenotype of ATTR-CM. CONCLUSIONS: There has been a significant increase in the rate of wtATTR-CM diagnoses in women, who presented with clear phenotypes of ATTR-CM. Further studies are needed to understand the effect of increased recognition of ATTR-CM in women on disease epidemiology, natural history, and outcomes.

Routine ambulatory heart rhythm monitoring for detection of atrial arrhythmias in transthyretin cardiac amyloidosis.

BACKGROUND: Atrial fibrillation and flutter (AF/AFL) are common in transthyretin cardiac amyloidosis (ATTR-CM) which in turn is associated with higher risk of thromboembolism. Detecting AF/AFL may be especially important, but the role of routine ambulatory monitoring in ATTR-CM patients is unclear. OBJECTIVE: The objective is therefore to determine prevalence and outcomes of subclinical AF/AFL on routine ambulatory rhythm monitoring. METHODS: We report outcomes of an observational study of patients at our Amyloidosis Center with wild-type or variant ATTR-CM diagnosed between 2005 and 2019. Patients without known AF/AFL at baseline had ambulatory ECG monitoring (duration 2-30 days) every 6 months while those with cardiovascular implantable electronic devices (CIEDs) had device interrogations instead. RESULTS: Eighty-four patients with ATTR-CM (mean age 73.5 ± 9.7 years, 94% male) had mean follow-up 2.3 ± 1.9 years. Forty patients (48%) had AF/AFL before ATTR-CM diagnosis. In the remainder, 21 (48%) were subsequently diagnosed with AF/AFL: 10 (48%) based on symptoms, and 11 (52%) by monitoring. Anticoagulation (AC) was started in 9/11 (82%) patients with incidental AF/AFL. Among the entire cohort, stroke occurred in 9 patients (11%): 1 hemorrhagic and 8 ischemic (7 in patients with AF/AFL). No strokes occurred in patients on AC. CONCLUSION: Almost half of patients in our cohort had AF/AFL diagnosed prior to their ATTR-CM diagnosis. In the remainder, approximately half of AF/AFL diagnoses were established incidentally by routine monitoring, most of whom were promptly anticoagulated. Incidence of stroke was high overall, but no strokes occurred in anticoagulated patients. Optimal frequency and duration of monitoring needs further investigation.

Navigating the Complex Web of Prescribing Amyloidosis Therapeutics: A Primer.

Advancement in the diagnosis and treatment of transthyretin amyloid cardiomyopathy has made great strides in recent years. Novel therapeutics for transthyretin amyloidosis such as tafamidis, patisiran, and inotersen have shown significant benefits in a not-so-rare disease but come with high listing price tags ranging from a quarter to more than a half million dollars per year. These costs create significant financial barriers for the majority of patients, especially those with existing Medicare insurance plans. Of 72 patients reviewed, 67% were Medicare beneficiaries. Financial assistance was explored for the majority, and 37 (51%) patients with Medicare Part D received financial assistance that reduced their copayments to $0. Only one-third of our patients were able to afford these medications without any forms of financial assistance. Of these patients, 4 (6%) had the highest copayments ranging from $13 000 to $15 000 per year. To navigate the complexities of prescribing and affordability in amyloidosis, a multidisciplinary team including a dedicated clinical pharmacist is crucial in guaranteeing patients' success to secure these novel therapeutics. In this article, we discuss our experiences with prescribing, acquiring insurance authorizations, and financing these life-saving medications based on patient-specific insurance plans and socioeconomic status.

Mode of death and outcomes of implantable cardioverter defibrillators in transthyretin amyloid cardiomyopathy.

INTRODUCTION: Transthyretin cardiac amyloidosis (ATTR-CM) may associate with sudden cardiac death. We report on the mode of death and outcomes with implantable cardioverter defibrillators (ICDs) in a cohort with ATTR-CM. METHODS: A single center observational cohort study of patients with ATTR-CM diagnosed between 2005 and 2019. ICD implant was at discretion of treating cardiologists. Medians are expressed with 25th,75th percentiles. RESULTS: Eighty-four patients with ATTR-CM (age 73.5 ± 9.7 years, 94% male, median follow-up 21.1 months (11.4-38.1). Nineteen patients (23%) underwent ICD implantation - 18 for primary and 1 for secondary prevention. In the primary prevention ICD group, 1 patient had 2 inappropriate shocks, 1 patient had appropriate ATP on 3 occasions. One patient (mixed ischemic cardiomyopathy and ATTR-CM) with secondary prevention ICD had 15 appropriate shocks in 3 episodes of VT storm. In patients without ICD, ambulatory monitoring review (14,764 h) did not reveal sustained ventricular arrhythmia. Excluding the one patient with secondary prevention ICD, 5 (28%) in the primary prevention ICD group and 22 (34%) in the non-ICD group died, p = 0.14. Mode of death did not vary between both groups. CONCLUSIONS: Patients with ATTR-CM and primary prevention ICD infrequently receive appropriate device therapy without differing in mode of death, which was mainly related to progressive heart failure, compared to those without ICD.

Targeted treatments of AL and ATTR amyloidosis.

The therapeutic landscape for cardiac amyloidosis is rapidly evolving. In the last decade, our focus has shifted from dealing with the inevitable complications of continued extracellular infiltration of amyloid fibrils to earlier identification of these patients with prompt initiation of targeted therapy to prevent further deposition. Although much of the focus on novel targeted therapies is within the realm of transthyretin amyloidosis, light chain amyloidosis has benefited due to an overlap particularly in the final common pathway of fibrillogenesis and extraction of amyloid fibrils from the heart. Here, we review the targeted therapeutics for transthyretin and light chain amyloidosis. For transthyretin amyloidosis, the list of current and future therapeutics continues to evolve; and therefore, it is crucial to become familiar with the underlying mechanistic pathways of the disease. Although targeted therapeutic choices in AL amyloidosis are largely driven by the hematology team, the cardiac adverse effect profiles of these therapies, particularly in those with advanced amyloidosis, provide an opportunity for early recognition to prevent decompensation and can help inform recommendations regarding therapy changes when required.

Management Strategies for Atrial Fibrillation and Flutter in Patients with Transthyretin Cardiac Amyloidosis.

Atrial fibrillation (AF) and flutter (AFL) frequently complicate transthyretin cardiac amyloidosis (ATTR-CM). Management poses challenges as rate control drugs are poorly tolerated and data addressing tolerability and efficacy of rhythm control is limited. We report outcomes of AF/AFL in ATTR-CM in a single center observational study of patients seen at our Amyloidosis Center with wild-type or hereditary ATTR-CM diagnosed between 2005-2019 including 84 patients (average age 74 ± 10 years, 94% male) with 27.6 ± 22.8 months follow-up. AF/AFL occurred in 61 patients (73%). Rapid ventricular response was common as was attempted rate control. However, discontinuation of rate control drugs was frequent (80%), often for adverse effects. Rhythm control was attempted in 64%, usually with cardioversion (DCCV) or ablation. Post-DCCV recurrence was common (91%) and time to recurrence was similar with or without anti-arrhythmic drugs (5.8 months (IQR 1.9-12.5) vs 6.2 months (IQR 1.9-12.5) p = 0.83). Ablation was performed in 23% with AFL (all for typical AFL) with 14% recurrence after mean of 60.9 months. Ablation for AF was performed in 12% with 86% recurrence after median of 6.2 months (IQR 5.6-12.3). Most patients (62%) with rhythm control had subjective improvement (≥1 NYHA class or resolved palpitations). In conclusion, AF/AFL was common in our cohort. Rate control was poorly tolerated and often abandoned. Rhythm control led to symptomatic improvement in a majority of cases, but durable success was limited. DCCV was modestly successful and not significantly improved with anti-arrhythmics. Ablation was successful with typical AFL but had limited success in AF.