Contemporary Therapies and Future Directions in the Management of Hypertrophic Cardiomyopathy.

Hypertrophic cardiomyopathy (HCM) is a genetic disorder caused by pathogenic variants in sarcomeric genes, leading to left ventricular hypertrophy and complex phenotypic heterogeneity. While HCM is the most common inherited cardiomyopathy, pharmacological treatment options have previously been limited and were predominantly directed towards symptom control owing to left ventricular outflow obstruction. These therapies, including beta blockers, calcium channel blockers, and disopyramide, have not been shown to affect the natural history of the disease, which is of particular concern for younger patients who have an increased lifetime risk of experiencing arrhythmias, heart failure, and sudden cardiac death. Increased knowledge of the genetic mechanisms underlying this disease in recent years has led to the development of targeted, potentially disease-modifying therapies for both obstructive and nonobstructive phenotypes that may help to prevent or ameliorate left ventricular hypertrophy. In this review article, we will define the etiology and clinical phenotypes of HCM, summarize the conventional therapies for obstructive HCM, discuss the emerging targeted therapies as well as novel invasive approaches for obstructive HCM, describe the therapeutic advances for nonobstructive HCM, and outline the future directions for the treatment of HCM.

Telemedicine may increase visit completion rates in postpartum patients with preeclampsia.

Postpartum cardiovascular (CV) evaluation of women with preeclampsia is recommended to screen for and treat modifiable risk factors to reduce lifetime CV risk. However, attendance at in-person postpartum obstetric and cardiology clinic visits is low. The aim of this study was to compare the completion rate of new patient telemedicine visits to in-person office visits for patients with preeclampsia referred for postpartum hypertension management and CV risk assessment at a single center. There were 236 unique new patient visits scheduled during the study period. The average age was 30.3 years, 73.7% patients were Black, and 56.7% had Medicaid insurance. The completion rate was 32% for in-person clinic visits and 70% for telemedicine visits. Women who did not complete an office visit were more likely to be Black (87% vs. 56%, p < 0.01) and younger (29.1 vs. 31.4 years, p = 0.04) compared to those who completed a visit. Notably, this difference was not seen with telemedicine visits. Telemedicine may provide a novel opportunity to improve the care for blood pressure management and CV risk reduction in a vulnerable population at risk of premature CV disease.

A genome-first approach to rare variants in hypertrophic cardiomyopathy genes MYBPC3 and MYH7 in a medical biobank.

'Genome-first' approaches to analyzing rare variants can reveal new insights into human biology and disease. Because pathogenic variants are often rare, new discovery requires aggregating rare coding variants into 'gene burdens' for sufficient power. However, a major challenge is deciding which variants to include in gene burden tests. Pathogenic variants in MYBPC3 and MYH7 are well-known causes of hypertrophic cardiomyopathy (HCM), and focusing on these 'positive control' genes in a genome-first approach could help inform variant selection methods and gene burdening strategies for other genes and diseases. Integrating exome sequences with electronic health records among 41 759 participants in the Penn Medicine BioBank, we evaluated the performance of aggregating predicted loss-of-function (pLOF) and/or predicted deleterious missense (pDM) variants in MYBPC3 and MYH7 for gene burden phenome-wide association studies (PheWAS). The approach to grouping rare variants for these two genes produced very different results: pLOFs but not pDM variants in MYBPC3 were strongly associated with HCM, whereas the opposite was true for MYH7. Detailed review of clinical charts revealed that only 38.5% of patients with HCM diagnoses carrying an HCM-associated variant in MYBPC3 or MYH7 had a clinical genetic test result. Additionally, 26.7% of MYBPC3 pLOF carriers without HCM diagnoses had clear evidence of left atrial enlargement and/or septal/LV hypertrophy on echocardiography. Our study shows the importance of evaluating both pLOF and pDM variants for gene burden testing in future studies to uncover novel gene-disease relationships and identify new pathogenic loss-of-function variants across the human genome through genome-first analyses of healthcare-based populations.

DRESS is a Mess: A Case of Cross Reactivity Between Lacosamide and Lamotrigine.

Drug reaction with eosinophilia with systemic symptoms (DRESS) syndrome is a rare drug reaction often presenting with both cutaneous manifestations and potentially life-threatening internal organ involvement. The precise incidence of DRESS is still unclear as it is easily missed due to its highly variable clinical presentation. However, with an expected mortality rate of approximately 10 percent, it is important for clinicians to be familiar with pharmacologic etiologies commonly implicated in the pathogenesis. We present a case of DRESS syndrome attributed to cross-reactivity between two commonly used anticonvulsants- lacosamide and lamotrigine.

Eluxadoline-induced pancreatitis occurring in an adult man without a prior cholecystectomy.

Eluxadoline is a novel medication that was approved in the USA in 2015 for the treatment of diarrhoea-predominant irritable bowel syndrome. Due to its unique mechanism of action as both an opioid agonist and antagonist, it has been placed as a schedule IV controlled substance. Since its approval, there have been several cases of eluxadoline-induced pancreatitis reported in the literature. The majority of patients who presented with eluxadoline-induced pancreatitis were reported to have had a prior cholecystectomy. Due to this, the Food and Drug Administration released a warning in 2017 that eluxadoline should no longer be used in patients who do not have a gall bladder. We present a rare case of an adult man without prior cholecystectomy who presented with severe mid-epigastric pain and was found to have eluxadoline-induced pancreatitis.

A 'Bit' of Appendicitis: A Case of a Foreign Object in the Adult Appendix.

Appendicitis is the most common abdominal surgical emergency, and if left untreated, can lead to an abscess, peritonitis, or even death. The exact mechanism of appendicitis has yet to be elucidated, but the predominant theory is that different forms of luminal obstruction of the vermiform appendix lead to ischemia of the appendix wall and subsequent translocation of bacteria across the compromised mucosa, leading to transmural inflammation. The most common etiology is hyperplasia of lymphoid tissue in the mucosa, often secondary to infection and inflammation with gradual symptom onset. Rarer causes of obstruction include parasitic infiltration, fibrous bands, carcinoid syndrome, and foreign body ingestion and often have atypical or absent symptomatology, making diagnosis more challenging and complications more frequent. We present a rare case of foreign body-associated appendicitis with distal lodging in the appendix and highlight the importance of prophylactic appendectomy to avoid severe complications.

Multiple Myeloma in an Agricultural Worker Exposed to Pesticides.

Multiple myeloma (MM) is a neoplastic disorder characterized by the monoclonal proliferation of plasma cells in the bone marrow. It is estimated to account for only 1% of neoplastic diseases, and there is still a great deal of uncertainty about its precise etiology. Common risk factors with a proven association with MM include ionizing radiation exposure, age greater than 65, male gender, and the presence of monoclonal gammopathy of unknown significance (MGUS).More recently, research has shown that occupational exposures to pesticides also have a significant association with the development of MM. We present the case of an adult male who presented with rib pain, back pain, fevers, and progressive shortness of breath and was ultimately found to have multiple myeloma thought to be associated with occupational exposure to the pesticide captan.