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.

Prevalence and Outcomes of p.Val142Ile TTR Amyloidosis Cardiomyopathy: A Systematic Review.

BACKGROUND: The p.Val142Ile variant, predominantly found among people of African descent, is the most common cause of variant transthyretin amyloidosis and carriers predominantly develop a cardiomyopathy (variant transthyretin amyloidosis cardiomyopathy) phenotype. Yet, there are conflicting data on the prevalence and outcomes of p.Val142Ile variant carriers. METHODS: We performed a systematic review of the prevalence and outcomes of p.Val142Ile variant transthyretin amyloidosis cardiomyopathy among subjects of African descent. We found 62 relevant articles after searching the MEDLINE databases from 1980 to 2020 that reported data for ≈150 000 subjects. RESULTS: The reported worldwide prevalence of the p.Val142Ile variant is 0.3% to 1.6% in the general population. Among people of African descent, the reported prevalence from all studies ranges from 1.1% to 9.8%, but for studies with >1000 subjects, it is 3% to 3.5%. The prevalence of the p.Val142Ile variant in a region is dependent on the reported percentage of subjects who are of African descent in that region. p.Val142Ile variant transthyretin amyloidosis cardiomyopathy typically presents in the seventh to eighth decade of life and the majority of cases reported were male, with 25% to 38% diagnosed with atrial fibrillation. It was associated with a longitudinally worse quality of life and a lower adjusted survival compared with other types of transthyretin amyloidosis cardiomyopathy. CONCLUSIONS: The p.Val142Ile variant is the most common variant of the transthyretin gene with most carriers being of African descent. The true penetrance is unknown but the p.Val142Ile variant is associated with increased rates of incident heart failure and portends a lower overall survival. Increased awareness could lead to earlier diagnosis and improved heart failure outcomes among those of African descent, which is of increasing importance given the advent of novel therapeutics for this disease.

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.

Impact of Aortic Valve Replacement for Severe Aortic Stenosis on Perioperative Outcomes Following Major Noncardiac Surgery.

OBJECTIVE: To compare the incidence of major adverse cardiac events and death among severe aortic stenosis patients with and without aortic valve replacement (AVR) before noncardiac surgery. PATIENTS AND METHODS: We retrospectively evaluated 491 severe aortic stenosis patients undergoing non-emergency/non-urgent elevated-risk noncardiac surgery between January 1, 2000, and December 31, 2013, including 203 patients (mean age, 74±10 years, 63.5% men) with previous AVR and 288 patients (mean age, 77±12 years, 55.6% men) without prior AVR. RESULTS: The incidence of major adverse cardiac events was significantly lower in the AVR group (5.4% vs 20.5%; P<.001), primarily because of the lower incidence of new or worsening heart failure (2.5% vs 17.7%; P<.001), compared with the non-AVR group. No significant differences were observed between the groups with and without AVR in the incidence of death (2.5% vs 3.5%; P=.56), myocardial infarction (0.5% vs 1.4%; P=.48), ventricular arrhythmia (0.0% vs 0.7%; P=.51), or stroke (0.0% vs 0.7%; P=.51) at 30-days. At a median follow-up of 4.2 (interquartile range,1.3-7.5) years, overall mortality was significantly worse in patients without versus with AVR (5-year rate: 57.0% vs 32.7%; P<.001). Symptomatic patients without AVR (n=35) had the worst outcomes overall, including increased 30-day and overall mortality rates, compared with the AVR-group and asymptomatic non-AVR patients. CONCLUSION: In patients with severe aortic stenosis, AVR before noncardiac surgery was associated with decreased incidence of heart failure after noncardiac surgery and improved overall survival without differences in 30-day survival, myocardial infarction, ventricular arrhythmia, or stroke. Preoperative AVR should be considered in symptomatic patients for whom the benefit of AVR is greatest.

Coronary artery bypass grafting in patients treated with thoracic radiation: a case-control study.

Background and aim: Thoracic radiation therapy (XRT) for cancer is associated with the development of significant coronary artery disease that may require coronary artery bypass grafting surgery (CABG). Contemporary acute surgical outcomes and long-term postoperative survival of patients with prior XRT have not been well characterised. Methods: This was a retrospective, single-centre study of patients with a history of thoracic XRT who required CABG and who were propensity matched against 141 controls who underwent CABG over the same time period. The objectives were to assess early CABG outcomes and long-term survival in patients with prior XRT. Results: Thirty-eight patients with a history of previous thoracic XRT underwent CABG from 1994 to 2013. The median time from XRT exposure to surgery was 7.9 years (IQR: 2.5-18.4 years). Perioperative adverse events were similar in the XRT group and controls; however, there was a trends lower utilisation of internal mammary artery (IMA) grafts in the XRT group (89%vs98%, P=0.13). After a median postoperative follow-up of 5.4 years (IQR 0.9-9.4 years), no difference in long-term all-cause mortality was observed. Conclusion: Patients with prior thoracic XRT who undergo CABG have similar long-term all-cause mortality compared with controls. Isolated CABG after thoracic XRT is not associated with higher perioperative complications, but IMA graft use may be limited by prior XRT.

Sex-stratified analysis of national trends and outcomes in isolated tricuspid valve surgery.

Objective: Female sex is a known risk factor for cardiac surgery, and tricuspid valve (TV) disease is more common in women. There are few data on sex-stratified surgical outcomes for isolated TV surgery. An administrative database was used to compare acute in-hospital outcomes between men and women undergoing isolated TV surgery. Methods: Patients aged >18 who underwent TV repair or replacement from 2004 to 2013 were identified using the National Inpatient Sample. Patients were excluded if they had congenital heart disease, endocarditis, or were undergoing concomitant cardiac surgeries except coronary bypass. Results were weighted to represent national averages. Sex-stratified analysis was performed using propensity score matching to compare in-hospital mortality, postoperative complications and hospital costs. Results: Over 10 years, women represented 58% of the 5005 TV surgeries performed. With propensity matching, hospital mortality (7.9% vs 7.7%; P=0.99) and median length of stay (11 vs 11 days; P=0.99) were similar between men and women. However, median hospital charges were higher for men ($166 000 vs $155 000; P=0.04). Conclusion: Isolated TV surgery is rare, but women more commonly undergo the procedure. In-hospital mortality was similar between men and women after propensity matching, but remains markedly high for both men and women in comparison to that reported for left-sided isolated valve surgery.

National Trends and Outcomes in Isolated Tricuspid Valve Surgery.

BACKGROUND: Severe isolated disease of the tricuspid valve (TV) is increasing and results in intractable right heart failure. However, isolated TV surgery is rarely performed, and there are little data describing surgical outcomes. OBJECTIVES: The purpose of this study was to evaluate contemporary utilization trends and in-hospital outcomes for isolated TV surgery in the United States. METHODS: Patients age >18 years who underwent TV repair or replacement from 2004 to 2013 were identified using the National Inpatient Sample. Patients with congenital heart disease, with endocarditis, and undergoing concomitant cardiac operations except for coronary bypass surgery were excluded. RESULTS: Over a 10-year period, a total of 5,005 isolated TV operations were performed nationally. Operations per year increased from 290 in 2004 to 780 in 2013 (p < 0.001 for trend). In-hospital mortality was 8.8% and did not vary across the study period. Adjusted in-hospital mortality for TV replacement was significantly higher than TV repair (odds ratio: 1.91; 95% confidence interval: 1.18 to 3.09; p = 0.009). CONCLUSIONS: Isolated TV surgery is rarely performed, although utilization has increased over time. However, despite an increase in surgical volume, operative mortality has not changed. Mortality is greatest in patients undergoing valve replacement. Given the increasing prevalence of isolated TV disease in the population, research into optimal surgical timing and patient selection is critical.

Intermediate care to intensive care triage: A quality improvement project to reduce mortality.

PURPOSE: Medical patients whose care needs exceed what is feasible on a general ward, but who do not clearly require critical care, may be admitted to an intermediate care unit (IMCU). Some IMCU patients deteriorate and require medical intensive care unit (MICU) admission. In 2012, staff in the Johns Hopkins IMCU expressed concern that patient acuity and the threshold for MICU admission were too high. Further, shared triage decision-making between residents and supervising physicians did not consistently occur. METHODS: To improve our triage process, we used a 4Es quality improvement framework (engage, educate, execute, evaluate) to (1) educate residents and fellows regarding principles of triage and (2) facilitate real-time communication between MICU residents conducting triage and supervising physicians. RESULTS: Among patients transferred from the IMCU to the MICU during baseline (n=83;July-December 2012) and intervention phases (n=94;July-December 2013), unadjusted mortality decreased from 34% to 21% (p=0.06). After adjusting for severity of illness, admitting diagnosis, and bed availability, the odds of death were lower during the intervention vs. baseline phase (OR 0.33; 95%CI 0.11-0.98). CONCLUSIONS: Using a structured quality improvement process targeting triage education and increased resident/supervisor communication, we demonstrated reduced mortality among patients transferred from the IMCU to the MICU.

Novel Use of MitraClip for Severe Mitral Regurgitation Due to Infective Endocarditis.

A 75-year-old man presented with infective endocarditis. Transesophageal echocardiogram (TEE) revealed mild-moderate mitral regurgitation (MR). After 4 weeks of antibiotics, he presented with New York Heart Association class III dyspnea. Repeat TEE demonstrated severe MR. After consultation with Infectious Diseases, it was determined the infection risk was low and transcatheter mitral valve repair (TMVR) was offered. Deployment of two MitraClip devices (Abbott Vascular) resulted in symptom relief. This case demonstrates a potential role of TMVR in treating acute severe MR due to endocarditis.