Showing papers by "Daniel J. Lenihan published in 2022"

Clinical and genetic profile of patients enrolled in the Transthyretin Amyloidosis Outcomes Survey (THAOS): 14-year update

Abstract: Abstract Background Transthyretin amyloidosis (ATTR amyloidosis) is a rare, life-threatening disease caused by the accumulation of variant or wild-type (ATTRwt amyloidosis) transthyretin amyloid fibrils in the heart, peripheral nerves, and other tissues and organs. Methods Established in 2007, the Transthyretin Amyloidosis Outcomes Survey (THAOS) is the largest ongoing, global, longitudinal observational study of patients with ATTR amyloidosis, including both inherited and wild-type disease, and asymptomatic carriers of pathogenic TTR mutations. This descriptive analysis examines baseline characteristics of symptomatic patients and asymptomatic gene carriers enrolled in THAOS since its inception in 2007 (data cutoff: August 1, 2021). Results This analysis included 3779 symptomatic patients and 1830 asymptomatic gene carriers. Symptomatic patients were predominantly male (71.4%) and had a mean (standard deviation [SD]) age of symptom onset of 56.3 (17.8) years. Val30Met was the most common genotype in symptomatic patients in South America (80.9%), Europe (55.4%), and Asia (50.5%), and more patients had early- versus late-onset disease in these regions. The majority of symptomatic patients in North America (58.8%) had ATTRwt amyloidosis. The overall distribution of phenotypes in symptomatic patients was predominantly cardiac (40.7%), predominantly neurologic (40.1%), mixed (16.6%), and no phenotype (2.5%). In asymptomatic gene carriers, mean (SD) age at enrollment was 42.4 (15.7) years, 42.4% were male, and 73.2% carried the Val30Met mutation. Conclusions This 14-year global overview of THAOS in over 5000 patients represents the largest analysis of ATTR amyloidosis to date and highlights the genotypic and phenotypic heterogeneity of the disease. ClinicalTrials.gov Identifier : NCT00628745.

Sex Differences in Wild-Type Transthyretin Amyloidosis: An Analysis from the Transthyretin Amyloidosis Outcomes Survey (THAOS)

Abstract: IntroductionWild-type transthyretin amyloidosis (ATTRwt amyloidosis) is a progressive disease resulting from the accumulation of wild-type transthyretin (TTR) amyloid fibrils, and is diagnosed primarily in males. This analysis examined sex differences in patients with ATTRwt amyloidosis from the Transthyretin Amyloidosis Outcomes Survey (THAOS).MethodsTHAOS is an ongoing, global, longitudinal, observational survey of patients with transthyretin amyloidosis, including both inherited and wild-type disease, and asymptomatic carriers of TTR mutations. THAOS data were analyzed to identify potential differences in demographic and clinical characteristics between males and females with ATTRwt amyloidosis (data cutoff: August 1, 2021).ResultsOf 1386 patients with ATTRwt amyloidosis, 84 (6%) were female and 1302 (94%) were male. Females had a higher median age at enrollment (80 vs. 78 years; p = 0.002) and symptom onset (75 vs. 73 years; p = 0.045) than males. Mean left ventricular (LV) ejection fraction was higher (53% vs. 48%; p = 0.001) and mean LV diastolic diameter lower (42 vs. 46 mm; p < 0.001) in females versus males, but sex was not identified as a predictor of LV mean wall thickness adjusted for height (beta coefficient − 0.22; p = 0.460) or a predominantly cardiac phenotype (odds ratio 1.60; p = 0.191). Modified polyneuropathy disability scores differed between groups (p < 0.001), with a larger proportion of scores ≥ IIIa among females (23% vs. 7%).ConclusionsFemales with ATTRwt amyloidosis in THAOS tended to present at a later age and showed signs of less severe cardiac impairment and more severe walking impairment.Trial RegistrationClinicalTrials.gov: NCT00628745.

Permissive Cardiotoxicity

Abstract: The field of cardio-oncology was born from the necessity for recognition and management of cardiovascular diseases among patients with cancer. This need for this specialty continues to grow as patients with cancer live longer as a result of lifesaving targeted and immunologic cancer therapies beyond the usual chemotherapy and/or radiation therapy. Often, potentially cardiotoxic anticancer treatment is necessary in patients with baseline cardiovascular disease. Moreover, patients may need to continue therapy in the setting of incident cancer therapy–associated cardiotoxicity. Herein, we present and discuss the concept of permissive cardiotoxicity as a novel term that represents an essential concept in the field of cardio-oncology and among practicing cardio-oncology specialists. It emphasizes a proactive rather than reactive approach to continuation of lifesaving cancer therapies in order to achieve the best oncologic outcome while mitigating associated and potentially off-target cardiotoxicities. • Permissive cardiotoxicity is a terminology that represents a vital concept in cardio-oncology • It emphasizes continued cancer therapy if appropriate, while mitigating cardiotoxicities. • Its application is guided by understanding the cancer treatment, alternatives, and prognosis.

Developing Therapy for Transthyretin Amyloidosis.

Abstract: Transthyretin amyloidosis (ATTR) is an under-recognized cause of cardiomyopathy and neuropathy. Until recently, there were limited therapeutic options for ATTR. However, new therapeutics including tafamidis, patisiran, and inotersen increase both quality and length of life of patients with ATTR. This review details the chronological development of ATTR therapies through landmark clinical trials. In addition, we discuss emerging ATTR therapies including improvements in drug delivery methods, antibodies to break-down deposited amyloid fibrils, and gene-editing. ATTR is a prime example of how an understanding of the pathophysiological basis of disease can lead to effective therapies. The future of ATTR therapy is bright with every reason to believe outcomes will continue to improve.

Future Developments in Light Chain Amyloidosis Management.

Abstract: Light chain (AL) amyloidosis is challenging to diagnose, and it should be considered a cardiac emergency. There have been a great deal of advances in the treatment of AL amyloidosis from initial descriptions of melphalan therapy until the recent approval of the first AL amyloidosis specific drug (daratumumab). Comprehension of the pathophysiology and biology of AL amyloidosis is crucial to understanding the major therapeutic targets in which light chain stability remains as a major key target of therapy. Organ dysfunction is a result not only from disruption of organ architecture but also direct cellular toxicity. Novel antiplasma cell agents for AL like isatuximab (anti CD-38 monoclonal antibody), belantamab (anti-BCMA monoclonal antibody), and elotuzumab (anti-SLAMF7 monoclonal antibody) are currently under investigation. Both diagnostic and therapeutic advances make the future of AL management bright while acknowledging the complexity of this patient population and focusing on a multidisciplinary approach.

No Diagnostic Concerns With Cardiovascular Magnetic Resonance Imaging in Patients With Breast Cancer and Breast Implants.

Abstract: Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Cardiology HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Cardiology journal

Implementing a Machine-Learning-Adapted Algorithm to Identify Possible Transthyretin Amyloid Cardiomyopathy at an Academic Medical Center

Abstract: Background: Wild-type transthyretin amyloid cardiomyopathy (ATTR-CM) is a frequently under-recognized cause of heart failure (HF) in older patients. To improve identification of patients at risk for the disease, we initiated a pilot program in which 9 cardiac/non-cardiac phenotypes and 20 high-performing phenotype combinations predictive of wild-type ATTR-CM were operationalized in electronic health record (EHR) configurations at a large academic medical center. Methods: Inclusion criteria were age >50 years and HF; exclusion criteria were end-stage renal disease and prior amyloidosis diagnoses. The different Epic EHR configurations investigated were a clinical decision support tool (Best Practice Advisory) and operational/analytical reports (Clarity™, Reporting Workbench™, and SlicerDicer); the different data sources employed were problem list, visit diagnosis, medical history, and billing transactions. Results: With Clarity, among 45 051 patients with HF, 4006 patients (8.9%) had ⩾1 phenotype combination associated with increased risk of wild-type ATTR-CM. Across all data sources, 2 phenotypes (cardiomegaly; osteoarthrosis) and 2 combinations (carpal tunnel syndrome + HF; atrial fibrillation + heart block + cardiomegaly + osteoarthrosis) generated the highest proportions of patients for wild-type ATTR-CM screening. Conclusion: All EHR configurations tested were capable of operationalizing phenotypes or phenotype combinations to identify at-risk patients; the Clarity report was the most comprehensive.

Hypertension is associated with more advanced heart failure in african americans with suspected cardiac amyloidosis

Abstract: Prior studies have shown worse clinical outcomes for African Americans with transthyretin and light chain cardiac amyloidosis as compared to Caucasians. Hypertensive heart disease is common among African Americans, and a known echocardiographic mimic of cardiac amyloidosis. The association between hypertension and heart failure severity in patients with suspected cardiac amyloidosis has not been well characterized. We sought to identify phenotypic differences between African American and Caucasian patients with suspected cardiac amyloidosis with and without hypertension. We retrospectively identified consecutive patients who underwent cardiac biopsy for evaluation of cardiac amyloidosis at our institution between 2000–2018. Clinical and demographic data were obtained from the medical record. Electrocardiograms and echocardiograms performed at the time of cardiac biopsy were interpreted by study personnel. Among 230 patients with suspected cardiac amyloidosis, 144 (58%) had a prior diagnosis of hypertension. Hypertension was more common among African Americans (71 of 91, 78%) than among Caucasians (73 of 139, 52%). Among African Americans with suspected cardiac amyloidosis, those with hypertension had higher left ventricular mass index (156 versus 119 g/m2), lower left ventricular ejection fraction (47% versus 56%), worse global longitudinal strain (−9.0% versus −11.7%), and higher creatine (1.95 versus 1.43 mg/dL) than those without hypertension (p<0.05 for all). There were no differences in these parameters among Caucasians with and without hypertension. Among African Americans with suspected cardiac amyloidosis, those with hypertension had worse systolic function and more advanced heart failure than those without hypertension. Targeted screening and/or surveillance strategies are needed to improve early diagnosis of cardiac amyloidosis in African American patients with hypertension. Type of funding sources: None.

Abstract P051: Hypertension Is Associated With All-cause Mortality In Caucasians But Not African Americans With Suspected Cardiac Amyloidosis

Abstract: Background: Diagnostic delay is common among patients with cardiac amyloidosis. Hypertensive heart disease is a known echocardiographic mimic of cardiac amyloidosis, with greater prevalence among African Americans than among Caucasians. The association between hypertension and clinical outcomes in patients with suspected cardiac amyloidosis is not known. Objective: We sought to determine the association between a known diagnosis of hypertension and all-cause mortality in African Americans and Caucasians with suspected cardiac amyloidosis. Methods: We identified 230 patients who underwent cardiac biopsy for suspected cardiac amyloidosis at our institution between 2000-2018. Clinical and demographic data were obtained from the medical record. Echocardiograms performed at the time of cardiac biopsy were interpreted by study personnel. All-cause mortality was assessed using the Social Security Death Index. Results: Among 230 patients with suspected cardiac amyloidosis, hypertension was more common among African Americans (71 of 91, 78%) than among Caucasians (73 of 139, 52%). Over a median follow-up period of 4.5 months, the all-cause mortality rate was higher among Caucasians with hypertension (67%) than Caucasians without hypertension (42%, p= 0.048). There was no difference in all-cause mortality rate among African Americans with and without hypertension (47.8% vs. 50%, p=0.903). Among Caucasians, those with hypertension had increased posterior wall thickness, relative wall thickness, and interventricular septal thickness as compared to those without hypertension (p<0.01 for all). There were no significant differences in these parameters among African Americans with and without hypertension (p>0.05). Conclusions: Hypertension and the hypertensive echocardiographic phenotype are associated with all-cause mortality in Caucasians but not African Americans with suspected cardiac amyloidosis. Additional study is needed to understand the differential effects of hypertension on clinical outcomes by racial category in patients with suspected cardiac amyloidosis.

Introduction to "Proceedings from Amyloidosis, A Hidden Disease with a Bright Future: A Multi-Disciplinary Approach to Diagnosis and Management of Amyloidosis".

Abstract: Amyloidosis is a heterogeneous disease that can be challenging to diagnose, frequently eluding even the most astute clinicians. Whether the clinical presentation is primarily cardiac, neurological, gastrointestinal, or renal in nature, symptoms are generally nonspecific and frequently attributed to more common causes of disease without consideration of amyloidosis. The multisystem nature of amyloidosis further complicates diagnosis. While characteristic patterns of multiorgan dysfunction can be a “red flag” finding that points to the correct diagnosis, all too often specialists fail to pick up on abnormal signs or symptoms outside of their own organ system. As a result, the diagnosis of amyloidosis is frequently delayed by many months from symptom onset, and the impact of targeted amyloid therapies on disease trajectory is accordingly reduced. Since 2018, several new and effective therapeutics have become clinically available for the treatment of transthyretin amyloidosis (patisiran, inotersen, tafamidis) and light chain amyloidosis (daratumumab). As a result, there has been a renewed interest in improving awareness of amyloidosis and diagnosing the disease earlier in its course, particularly within the Cardiology community. However, the vast majority of educational efforts remain confined within a single organ system, individually targeting subspecialty groups without a multidisciplinary approach. Starting in 2018, our faculty within the Amyloid Center of Excellence at Washington University School of Medicine in St. Louis has hosted an annual Continuing Medical Education (CME) symposium highlighting a multidisciplinary approach to the diagnosis and treatment of amyloidosis. On March 6, 2021, we held a virtual CME event titled “Amyloidosis: A Hidden Disease with a Bright Future” featuring international experts within the amyloidosis field in addition to our own faculty experts from Cardiology, Hematology/Oncology, Gastroenterology, Nephrology, Neurology, and Pathology. With great dedication from our speakers and their trainees, we have converted the lectures presented at the symposium into the 10 manuscripts included in this Supplement. We hope that this compilation will enhance a multidisciplinary understanding of amyloidosis for clinicians and trainees from all specialties. We are grateful to Alnylam Pharmaceuticals and Janssen Pharmaceuticals for providing financial support for the publication of this Supplement.

Abstract 13273: Real-World Efficacy of Tafamidis in Patients With Transthyretin Amyloidosis and Heart Failure

Abstract: Background: Tafamidis was associated with reduction in cardiovascular hospitalizations and all-cause mortality in patients with transthyretin amyloid cardiomyopathy (ATTR-CM) in the ATTR-ACT trial. However, real-world data on the efficacy of tafamidis are limited. Methods: We conducted a retrospective, observational cohort study using the TriNetX research network, a multicenter federated research network with data pooled from electronic health records. Patients with wild-type TTR amyloidosis and heart failure (HF) were identified based on ICD-10 codes on or before May 15, 2021. The study cohort was then divided into two groups based on treatment with tafamidis. Propensity score matching (PSM) was performed to balance the confounders. Rates of heart failure exacerbations (HFE) and all-cause mortality at 12 months were compared between the two cohorts. Results: We identified 1362 patients with wild-type ATTR amyloidosis with HF (tafamidis group =553, non-tafamidis group =809). After PSM, there were 421 patients in each group (mean age: 76 years, Female 14%, White race 64%). During the 12-month follow-up period, 38 (9.0%) patients experienced HFE in the tafamidis group compared to 58 (13.8%) patients in the non-tafamidis group (OR 0.62; CI0.40-0.95, p=0.030). Patients treated with tafamidis had lower all-cause mortality compared to the non-tafamidis group (10.7% vs. 16.4%; OR 0.61, CI 0.40-0.91, p=0.016). The treated cohort had a higher probability of event-free survival for HFE (HR 0.61; 95% CI 0.40-0.92, Log-Rank p= 0.018) and all-cause mortality (HR 0.619; 95% CI 0.425, 0.901, Log-Rank p= 0.011). Conclusion: This real-world analysis confirms that tafamidis use is associated with reduced HF exacerbations and all-cause mortality in patients with wild-type TTR amyloidosis and HF. Longer term follow-up is needed to better understand the utility of tafamadis given the increasing recognition of ATTR-CM and its high cost.

Abstract 11850: Association Between SGLT2 Inhibitor Use and Risk of Clinical Events in Patients With Antineoplastic Therapy Associated Cardiomyopathy and Heart Failure

Abstract: Background: Antineoplastic therapies can be cardiotoxic and increase the risk of cardiomyopathy and heart failure (HF). SGLT2i are shown to be efficaceous in patients across the spectrums of HF regardless of ejection fraction and presence of type 2 diabetes. However, the impact of these agents on outcomes in patients with antineoplastic therapy associated cardiomyopathy and HF has not been well established. Methods: A retrospective cohort analysis was performed on de-identified, aggregate patient data from the TriNetX research network. Patients ≥18 years of age with a history of exposure to potentially cardiotoxic antineoplastic therapy between Jan 1, 2013 and Apr 30, 2020 who subsequently developed cardiomyopathy or HF and treated with guideline directed medical therapy (GDMT) were identified. Patients with ischemic heart disease were excluded. Patients were divided into two groups based on SGLT2i use. Propensity score matching was performed to match the baseline characteristics. Odds ratio and log-rank test were used to compare the outcomes over a 2-year follow-up period. Results: In well matched cohorts (640 patients in each cohort with antineoplastic therapy associated cardiomyopathy/HF; mean age 67.6 years, women 41.6%, White 68%), patients on SGLT2i in addition to conventional GDMT faced lower risk of acute HF exacerbation (85 vs 154, OR 0.48, 95% CI: 0.36 - 0.65, p<0.001) and all-cause mortality (73 vs 194, OR 0.30, 95% CI: 0.22 - 0.40, p=0.001). Secondary outcomes of all-cause hospitalization or ER visit (OR 0.479, 95% CI: 0.383-0.599, p<0.001), atrial fibrillation/flutter (OR 0.397, 95% CI: 0.213-0.737, p=0.003), acute kidney injury (OR 0.486, 95% CI: 0.382-0.619, p<0.001), and renal replacement therapy (OR 0.398, 95% CI: 0.189-0.839, p=0.012) were also less frequent in patients on SGLT2i. Conclusions: SGLT2i use is associated with lower risk of clinical events in patients with antineoplastic therapy associated cardiomyopathy or HF.

Global pattern of cardiovascular disease management in patients with cancer and impact of COVID-19 on drug selection: IRAQ—IC-OS survey-based study

Abstract: Background Regional variations in cardiovascular disease (CVD) and CVD management are well known. However, there is limited information on geographical variations in the discipline of Cardio-Oncology, including both the nature of CVD in patients with cancer and its management. Furthermore, during the recent COVID-19 pandemic, CV care for patients was disrupted resulting in an unknown impact on cardio-oncology services. Objective The aim of this study was to identify the regional variations in the management of CVD among patients with cancer and the impact of the COVID-19 pandemic on the selection of cardiovascular drugs in cardio-oncology. Methods An online survey was conducted by the Iraq Chapter of the International Cardio-Oncology Society (IC-OS). The survey was shared with cardiologists and oncologists in all seven continents to identify whether regional variations exist in cardio-oncology daily practice. Results From April to July 2021, 140 participants responded to the survey, including cardiologists (72.9%) and oncologists (27.1%). Most of the respondents were from the Middle East (26.4%), North America (25%), Latin America and the Caribbean (25%), and Europe (20.7%). Baseline CV risk assessment in patients with cancer using the HFA/IC-OS score was reported in 75.7% of respondents (78.4% cardiologists and 68.4% oncologists). Hypertension was the most common CVD treated by the survey respondents globally (52.1%) unlike in Europe where heart failure was the most prominent CVD (51.7%). The blood pressure cutoff value to initiate hypertension management is >140/90 mmHg globally (72.9%), but in North America (48.6%) it was >130/80 mmHg. In the Middle East, 43.2% of respondents do not use cardioprotective medication. During the COVID-19 pandemic, 10.7% of respondents changed their practice, such as switching from prescribing ACEI to ARB. Apixaban is the main anticoagulant used in patients with cancer (32.9%); however, in cancer patients with COVID-19 infection, the majority used enoxaparin (31.4%). Conclusion More than three-quarters of cardiologists and oncologists responding to the survey are using HFA/IC-OS proformas. The survey showed regional variations in the management of CVD on different continents. The use of cardioprotective agents was limited in some regions including the Middle East. COVID-19 pandemic impacted daily practice on the selection and switching of cardiovascular drugs including ACEI/ARB and the choice of anticoagulants.