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

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.

Real-world safety of neurohormonal antagonist initiation among older adults following a heart failure hospitalization.

AIMS: To optimize guideline-directed medical therapy for heart failure, patients may require the initiation of multiple neurohormonal antagonists (NHAs) during and following hospitalization. The safety of this approach for older adults is not well established. METHODS AND RESULTS: We conducted an observational cohort study of 207 223 Medicare beneficiaries discharged home following a hospitalization for heart failure with reduced ejection fraction (HFrEF) (2008-2015). We performed Cox proportional hazards regression to examine the association between the count of NHAs initiated within 90 days of hospital discharge (as a time-varying exposure) and all-cause mortality, all-cause rehospitalization, and fall-related adverse events over the 90 day period following hospitalization. We calculated inverse probability-weighted hazard ratios (IPW-HRs) with 95% confidence intervals (CIs) comparing initiation of 1, 2, or 3 NHAs vs. 0. The IPW-HRs for mortality were 0.80 [95% CI (0.78-0.83)] for 1 NHA, 0.70 [95% CI (0.66-0.75)] for 2, and 0.94 [95% CI (0.83-1.06)] for 3. The IPW-HRs for readmission were 0.95 [95% CI (0.93-0.96)] for 1 NHA, 0.89 [95% CI (0.86-0.91)] for 2, and 0.96 [95% CI (0.90-1.02)] for 3. The IPW-HRs for fall-related adverse events were 1.13 [95% CI (1.10-1.15)] for 1 NHA, 1.25 [95% CI (1.21-1.30)] for 2, and 1.64 [95% CI (1.54-1.76)] for 3. CONCLUSIONS: Initiating 1-2 NHAs among older adults within 90 days of HFrEF hospitalization was associated with lower mortality and lower readmission. However, initiating 3 NHAs was not associated with reduced mortality or readmission and was associated with a significant risk for fall-related adverse events.

Association of early electrical changes with cardiovascular outcomes in immune checkpoint inhibitor myocarditis.

BACKGROUND: Immune-checkpoint inhibitor-associated myocarditis (ICI-myocarditis) often presents with arrhythmias, but the prognostic value of early electrocardiogram findings is unclear. Although ICI-myocarditis and acute cellular rejection (ACR) following cardiac transplantation use similar treatment strategies, differences in arrhythmia burden are unknown. OBJECTIVE: To evaluate the association of electrocardiogram findings in ICI-myocarditis with myocarditis-related mortality and life-threatening arrhythmia. METHODS: A total of 125 cases of ICI-myocarditis were identified retrospectively across 49 hospitals worldwide; 50 cases of grade 2R or 3R ACR were included as comparators. Two cardiologists blinded to clinical data interpreted electrocardiograms. Associations between electrocardiogram features, myocarditis-related mortality and the composite of myocarditis-related mortality and life-threatening arrhythmias were examined. Adjusted hazard ratios (aHRs) were calculated. RESULTS: The cohort had 78 (62.4%) men; median (interquartile range) age was 67 (58-76) years. At 30 days, myocarditis-related mortality was 20/124 (16.1%), and 28/124 (22.6%) met the composite endpoint. Patients who developed complete heart block (aHR by subdistribution hazards model [aHR(sh)] 3.29, 95% confidence interval [CI] 1.24-8.68; P=0.02) or life-threatening cardiac arrhythmias (aHR(sh) 6.82, 95% CI: 2.87-16.21; P<0.001) had a higher risk of myocarditis-related mortality. Pathological Q waves (aHR(sh) 3.40, 95% CI: 1.38-8.33; P=0.008), low QRS voltage (aHR(sh) 6.05, 95% CI: 2.10-17.39; P<0.001) and Sokolow-Lyon index (aHR(sh)/mV 0.54, 95% CI: 0.30-0.97; P=0.04) on admission electrocardiogram were also associated with increased risk of myocarditis-related mortality. These associations were mirrored in the composite outcome analysis. Compared with ACR, ICI-myocarditis had a higher incidence of life-threatening cardiac arrhythmias (15/125 [12.0%] vs 1/50 [2%]; P=0.04) and third-degree heart block (19/125 [15.2%] vs 0/50 [0%]; P=0.004). CONCLUSIONS: Electrocardiograms in ICI-myocarditis with ventricular tachycardias, heart block, low-voltage and pathological Q waves were associated with myocarditis-related mortality and life-threating arrhythmia. Arrhythmia burden in ICI-myocarditis exceeds that of ACR after heart transplant.

Oncocytic Papillary Cystadenoma, an Unusual Variant Presenting as a Laryngeal Ventricular Cyst.

Cystadenoma arising from the larynx is a rare benign minor salivary gland tumor that can show mucinous or papillary morphology. The epithelial lining of the salivary gland tumor can present with oncocytic features, which is attributed to an increased number of mitochondria. We present a rare case of oncocytic papillary cystadenoma (OPC) of the larynx which has a combination of these features. The WHO defines OPC tumors as entities which closely resemble Warthin tumor, but lack its classic lymphoid component. The immunohistochemical profile and molecular genetic features are largely unknown. We present an 84-year-old female, former smoker, who presented with progressive dysphonia, dysphagia, and shortness of breath. Laryngoscopy revealed a large, smooth mass originating from the ventricle of the right vocal fold. Subsequent biopsy demonstrated cyst wall fragments lined by a bilayer of large columnar to cuboidal oncocytic cells that had granular eosinophilic cytoplasm, round to oval nuclei with finely dispersed chromatin, and small but distinct nucleoli. The surrounding stroma was slightly fibrotic with scant lymphoid elements. No nuclear pleomorphism, increased mitosis, or necrosis was identified. In the larynx, benign salivary gland tumors are rare and less frequent than malignant neoplasms. Awareness of rare benign entities like OPC help ensure proper management and aid in avoiding unnecessary therapy.

Prognostic Value of Lymph Node Ratio in Cutaneous Melanoma: A Systematic Review.

The prognosis of cutaneous melanoma (CM) is based on the histological characteristics of the primary tumor, such as Breslow depth, ulceration, and mitotic rate. The lymph node ratio (LNR) is the ratio of the involved lymph nodes (LNs) divided by the total number of LNs removed during regional LN dissection. LNR is a prognostic factor for many solid tumors; however, controversies exist regarding CM. This study sought to analyze the role of LNR as a prognostic factor in CM. An extensive literature search was conducted using PubMed, Google Scholar, Medline, and the Cochrane Central Registry of Controlled Trials from January 1966 to July 2015. The keywords included in the search were CM and inclusion of the ratio of positive to the total number of LNs as a prognostic factor. The outcomes analyzed included the number of patients with positive LNs, type of survival analysis, and results from the multivariate analysis. A total of 11 studies involving 12,011 patients with positive LNs were evaluated. No previous randomized controlled trials, meta-analyses, or systematic reviews were identified in the Cochrane database on the prognostic value of LNR in CM. The primary electronic database search resulted in 333 full-text articles. The LN location examined was the cervical, axillary, and inguinal regions in all studies except for one that examined only the inguinal region. All studies except three studied the prognostic value of the LNR as a categorical variable rather than a continuous variable. LNR was categorized as A (≤0.1), B (0.11-0.25), and C (>0.25). All studies identified LNR as an independent predictor of overall survival (OS), disease-free survival (DFS), or disease-specific survival (DSS). The hazard ratio (HR) and confidence interval (CI) associated with either DFS or OS were available only in a few studies. Moreover, pooled HR for OS was 2.08 (95% CI: 1.48 2.92), for DFS was 1.364 (95% CI: 0.92-2.02), and for DSS was 1.643 (95% CI: 0.89-3.0). The LNR provides superior prognostic stratification among patients with CM. Additional adequately powered prospective studies are needed to further define the role of LNR and be included in the staging system of CM and direct adjuvant therapy.

Frequency of Celiac Disease in Patients With Chronic Diarrhea.

INTRODUCTION: Celiac disease (CD) is an immune-mediated disease caused by ingesting gluten-containing foods and is characterized mainly by malabsorptive diarrhea. Furthermore, distinguishing between mild disease and asymptomatic individuals is critical and necessitates a high level of clinical suspicion. Short stature, delayed puberty, bone abnormalities, neurological problems, and intestinal cancer can all be consequences of a delayed diagnosis. This study aimed to determine the prevalence of celiac disease among our community's recurrent diarrhea patients. METHODS: This was a cross-sectional study aimed at determining the frequency of celiac disease in patients with chronic diarrhea. One hundred eighty-eight patients between the ages of 18 and 60 years who had chronic diarrhea lasting greater than three months were enrolled in this study. Stratification was utilized to control for modifiers. A p-value of ≤ 0.05 was considered significant. RESULTS: A total of 74.5% of patients (n=140) were male, while 25.5% (n=48) were female with a mean age of 38.48±10.85 years. The average duration of celiac disease symptoms was 8.17± 3.75 months. Celiac disease was found in 12.2% (n=23) of the individuals. Also, 21% of individuals with a positive family history of CD devolved CD, compared to those without prior CD family history (p=0.01). CONCLUSIONS: In individuals with chronic diarrhea for more than three months, the prevalence of celiac disease was determined to be 12.2% (n=23). There was a statistically significant difference between those with a positive family history of CD and those who did not have the condition.

Epidemiology of Cardiac Amyloidosis-Associated Heart Failure Hospitalizations Among Fee-for-Service Medicare Beneficiaries in the United States.

Background Cardiac amyloidosis is a substantially underdiagnosed disease, and contemporary estimates of the epidemiology of amyloidosis are lacking. This study aims to determine the incidence and prevalence of cardiac amyloidosis among Medicare beneficiaries from 2000 to 2012. Methods and Results Medicare beneficiaries were counted in the prevalence cohort in each year they had (1) ≥1 principal or secondary International Classification of Diseases, Ninth Revision code for amyloidosis and (2) ≥1 principal or secondary International Classification of Diseases, Ninth Revision code for heart failure or cardiomyopathy within 2 years after the systemic amyloidosis code. A beneficiary was counted in the incidence cohort only during the first year in which they met criteria. Primary outcomes included the prevalence and incidence of hospitalizations for cardiac amyloidosis. There were 4746 incident cases of cardiac amyloidosis in 2012 and 15 737 prevalent cases in 2012. There was also a significant increase in the prevalence rate (8 to 17 per 100 000 person-years) and incidence rate (18 to 55 per 100 000 person-years) from 2000 to 2012, most notable after 2006. Incidence and prevalence increased substantially more among men, the elderly, and in blacks. Conclusions The incidence and prevalence rates of cardiac amyloidosis are higher than previously thought. The incidence and prevalence rates of cardiac amyloidosis among hospitalized patients have increased since 2000, particularly among specific patient subgroups and after 2006, suggesting improved amyloidosis awareness and higher diagnostic rates with noninvasive imaging. In light of these trends, cardiac amyloidosis should be considered during the initial work up of patients ≥65 years old hospitalized with heart failure.

Predictors of survival to orthotopic heart transplant in patients with light chain amyloidosis.

BACKGROUND: Orthotopic heart transplant (OHT), followed by myeloablative chemotherapy and autologous stem cell transplant (ASCT), has been successful in the treatment of amyloid light-chain (AL) cardiac amyloidosis. The purpose of this study was to identify predictors of survival to OHT in patients with end-stage heart failure due to AL amyloidosis and compare post-OHT survival of cardiac amyloid patients with survival of other cardiomyopathy patients undergoing OHT. METHODS: From January 2000 to June 2011, 31 patients with end-stage heart failure secondary to AL amyloidosis were listed for OHT at Massachusetts General Hospital. Univariate and multivariate regression analyses identified predictors of survival to OHT. Kaplan-Meier analysis compared survival between the Massachusetts General Hospital amyloidosis patients and non-amyloid cardiomyopathy patients from the Scientific Registry of Transplant Recipients (SRTR). RESULTS: Low body mass index was the only predictor of survival to OHT in patients with end-stage heart failure caused by cardiac amyloidosis. Survival of cardiac amyloid patients who died before receiving a donor heart was only 63 ± 45 days after listing. Patients who survived to OHT received a donor organ at 53 ± 48 days after listing. Survival of AL amyloidosis patients on the waiting list was less than patients on the waiting list for all other non-amyloid diagnoses. The long-term survival of amyloid patients who underwent OHT was no different than the survival of non-amyloid, restrictive (p = 0.34), non-amyloid dilated (p = 0.34), or all non-amyloid cardiomyopathy patients (p = 0.22) in the SRTR database. CONCLUSIONS: Amyloid patients who survive to OHT, followed by ASCT, have a survival rate similar to other cardiomyopathy patients undergoing OHT; however, 35% of the patients died awaiting OHT. The only predictor of survival to OHT in AL amyloidosis patients was a low body mass index, which correlated with a shorter time on the waiting list. To optimize the survival of these patients, access to donor organs must be improved.