Publications by authors named "Ronald M Witteles"
Article Synopsis
- - Hypertension (HTN) is the most common additional health issue found in cancer patients, affecting both those with pre-existing conditions and those who develop it due to cancer treatments.
- - Various cancer therapies, such as VEGF inhibitors, Bruton tyrosine kinase inhibitors, and proteasome inhibitors, have been linked to the onset of HTN in patients.
- - The causes of hypertension from these therapies can be due to direct effects on blood vessels (like with VEGF inhibition) or other unclear mechanisms not fully understood yet.
Importance: Transthyretin amyloid cardiomyopathy (ATTR-CM) is a progressive cardiomyopathy that commonly presents with concomitant chronic kidney disease. Chronic kidney dysfunction is associated with worse outcomes, but the prognostic value of changes in kidney function over time has yet to be defined.
Objective: To assess the prognostic importance of a decline in estimated glomerular filtration rate (eGFR) in a large cohort of patients with ATTR-CM.
Article Synopsis
- Transthyretin amyloidosis with cardiomyopathy (ATTR-CM) is a serious, progressive disease, and vutrisiran is a new treatment that works by reducing the production of transthyretin in the liver.
- In a double-blind trial involving 655 patients, those receiving vutrisiran had a lower risk of death and cardiovascular events compared to those on placebo, demonstrating significant efficacy.
- Vutrisiran also improved patient outcomes, showing less decline in walking distance and quality of life measurements over the study period compared to placebo.
Article Synopsis
- Chronic kidney disease is prevalent in patients with amyloid cardiomyopathy, prompting a study on tafamidis, which was previously approved for treating transthyretin amyloid cardiomyopathy (ATTR-CM) based on the ATTR-ACT trial.
- A post hoc analysis of the ATTR-ACT trial assessed renal function changes over 30 months among patients taking tafamidis versus a placebo, measuring estimated glomerular filtration rate (eGFR) and a composite endpoint of renal decline events.
- Results indicated that those treated with tafamidis experienced less decline in eGFR, improved CKD staging, and a lower rate of reaching critical renal failure events compared to the placebo
Article Synopsis
- Hereditary transthyretin amyloidosis with polyneuropathy (ATTR-PN) is caused by mutations in the TTR gene, leading to health complications.
- The study created two induced pluripotent stem cell (iPSC) lines from ATTR-PN patients with specific TTR mutations, which showed normal cell characteristics and the ability to differentiate into various cell types.
- These iPSC lines are important for studying ATTR-PN's mechanisms and developing patient-specific models for better understanding and potential treatments.
Article Synopsis
- Specific mutations in the TTR gene lead to hereditary ATTR amyloidosis, impacting the heart.
- Researchers created two human induced pluripotent stem cell (iPSC) lines from patients with a TTR mutation (p.Val30Met), demonstrating high pluripotency.
- These patient-derived iPSCs are valuable for studying amyloidosis mechanisms in different cell types and tissues.
Article Synopsis
- This study evaluated a new technique for detecting left ventricular hypertrophy (LVH) using ECGs, comparing it to existing methods to determine effectiveness.
- The retrospective analysis involved over 53,000 ECG and echocardiogram pairs, revealing that the new technique, called Witteles-Somani (WS), shows comparable performance to others like Sokolow-Lyon and Cornell.
- Results indicated that patients identified with LVH using the WS method faced a significantly increased risk of cardiovascular issues, including heart failure and mortality.
Comparative arrhythmia patterns among patients on tyrosine kinase inhibitors.
J Interv Card Electrophysiol
January 2024
Article Synopsis
- Tyrosine kinase inhibitors (TKIs), especially ibrutinib, are commonly used to treat blood cancers, but there are concerns about arrhythmias associated with these medications.
- A study analyzed 193 patients on long-term cardiac monitoring, revealing that those on ibrutinib had a significantly higher occurrence of atrial fibrillation and non-sustained ventricular tachycardia compared to those on other TKIs or non-TKI treatments.
- The findings suggest that 25% of ibrutinib patients had to pause their treatment due to arrhythmias, highlighting the need for careful heart monitoring in patients receiving this type of therapy.
Article Synopsis
- Trastuzumab, a treatment for HER2-overexpressing cancers, is linked to higher risks of heart failure (HF), particularly when compared to other anti-HER2 therapies.
- A study analyzed data from nearly 42,000 patients to compare the incidence of heart failure across various anti-HER2 treatments, including monoclonal antibodies, antibody-drug conjugates, and tyrosine kinase inhibitors.
- The results indicated that trastuzumab had significantly higher odds of heart failure reports compared to other anti-HER2 therapies, with the highest risks being associated with the combination therapy of trastuzumab and pertuzumab.
Article Synopsis
- - ICIs (Immune Checkpoint Inhibitors) in cancer treatment may lead to severe heart-related immune side effects.
- - Single-cell multi-omics are advanced methods that help identify and analyze different types of cells.
- - Utilizing multi-omics technology can reveal how ICI-induced myocarditis occurs and its underlying mechanisms.
Background: Transthyretin amyloid cardiomyopathy (ATTR-CM) is a fatal disease. Tafamidis was approved to treat patients with ATTR-CM based on findings from the ATTR-ACT (Tafamidis in Transthyretin Cardiomyopathy Clinical Trial).
Objectives: This post hoc analysis examined the proportion of patients who experienced improved efficacy measures through 30 months of treatment with tafamidis or placebo in ATTR-ACT.
Article Synopsis
- Recent research studied 209 patients with plasma cell dyscrasias (PCDs) to assess the prevalence and clinical implications of CHIP, identifying mutations in DNMT3A, TET2, and ASXL1.
- The study found a 19% prevalence of CHIP across various PCDs, with significant correlations to older age and cardiovascular issues in MM, but did not indicate worse overall survival or progression risk in MM or related conditions.
Tyrosine kinase inhibitor-associated ventricular arrhythmias: a case series and review of literature.
J Interv Card Electrophysiol
August 2023
Article Synopsis
- Tyrosine kinase inhibitors (TKIs) are commonly used for treating various cancers, but they may lead to serious cardiovascular issues, particularly ventricular arrhythmias (VAs), which are not well-studied compared to other heart conditions.
- A review of five patient cases from 2019 to 2022 found that VAs occurred in individuals with different heart health backgrounds, and these issues improved after stopping TKI therapy, although some needed additional heart medications or devices.
- The study emphasizes the importance of recognizing the risk of VAs from TKIs in cancer patients and suggests the need for better monitoring and treatment methods to manage these potential cardiovascular side effects.
Article Synopsis
- Immune checkpoint inhibitors (ICIs) are treatments that enhance the immune response against tumors but can lead to severe side effects like myocarditis, which has a high mortality rate.
- Researchers studied blood samples from 52 individuals, including those with autoimmune side effects from ICIs and healthy controls, using advanced techniques to identify specific immune cell changes related to ICI myocarditis.
- Findings revealed an increase in a specific type of immune cell, cytotoxic CD8 T effector cells, in patients with myocarditis, indicating a strong immune activation that could explain the condition's severity.
Article Synopsis
- The study reviews the quality and consistency of Medical Student Performance Evaluations (MSPE) from various accredited medical schools to assess adherence to AAMC recommendations and changes over time.
- Only 25% of the analyzed schools provided complete and compliant MSPE information in the latest evaluation period, with a wide range of grading practices leading to disparities among students.
- The research indicated notable grade inflation, with a 14% average increase in students receiving top grades in clerkships over a six-year span, highlighting potential issues in evaluation fairness.
Article Synopsis
- Immunoglobulin light chain amyloidosis is a rare disease that affects multiple organs such as the heart, kidneys, nerves, and digestive system, caused by improperly folded proteins that form harmful amyloid deposits.
- The prognosis for patients largely depends on the level of heart involvement and the effectiveness of treatment, with efforts to improve therapy development through partnerships like the one between the Amyloidosis Research Consortium and the FDA.
- The Cardiac Working Group aimed to identify key cardiovascular measures for clinical trials, focusing on factors like survival rates, hospitalization, and patient quality of life to improve treatment outcomes.
Racial and Ethnic Disparities in Transthyretin Cardiac Amyloidosis.
Curr Cardiovasc Risk Rep
June 2021
Article Synopsis
- ATTR-CM is a serious heart condition primarily affecting older adults and those of African descent, highlighting significant racial and ethnic health disparities.
- Recent studies reveal that ATTR-CM is more prevalent in older men and Black individuals, yet most research has focused on North American and European populations, neglecting those most affected.
- There is a need for earlier detection of ATTR-CM and increased participation of Black patients in clinical trials, along with better access to treatments for marginalized communities.
Article Synopsis
- - This text discusses a patient with pericardial amyloidosis linked to lymphoplasmacytic lymphoma, experiencing ongoing shortness of breath and coughing.
- - It emphasizes the diverse ways cardiac amyloidosis can present in patients, showcasing that symptoms can differ widely.
- - Additionally, it points out the uncommon but significant instances of light-chain and heavy-chain amyloidosis affecting the pericardium, which is the fibrous sac surrounding the heart.
Article Synopsis
- Ibrutinib, a medication for blood cancers, is linked to higher rates of atrial fibrillation (AF) and other heart rhythm issues, but there’s limited data on its effects on other types of arrhythmias.* -
- A study analyzed records of 72 patients using event monitors while on ibrutinib, revealing significant occurrences of supraventricular tachycardia, AF, and ventricular tachycardia, with 25% requiring treatment interruptions.* -
- The findings highlight a concerning prevalence of heart rhythm problems among patients on ibrutinib, suggesting a need for better diagnostic and management approaches for these side effects.*
Cardiac Transplantation and Mechanical Circulatory Support in Amyloidosis.
JACC CardioOncol
October 2021
Article Synopsis
- Cardiac transplants for amyloidosis used to be seen as too risky because of high complications and death rates.
- Advances in treatments for AL and ATTR amyloidosis and better screening have significantly improved transplant success in the last decade or so.
- There are few mechanical support options for patients, but they could be beneficial for certain individuals, especially those with larger heart chambers, highlighting a need to rethink how we prioritize heart transplants for amyloidosis patients, especially those with AL.
Article Synopsis
- Targeted therapies for driver-mutated metastatic non-small cell lung cancer (NSCLC) have improved treatment outcomes, but they come with cardiovascular risks such as heart failure and arrhythmias.
- A study analyzed data from the WHO pharmacovigilance database to compare the incidence of cardiovascular adverse events among various targeted therapy drugs, including EGFR, BRAF, MEK, and ALK/ROS1 inhibitors.
- Results indicated that ALK/ROS1 inhibitors have higher risks of conduction disease and QT prolongation, while osimertinib showed strong associations with multiple heart-related issues, highlighting the need for careful monitoring during treatment.