Real-world experience with mavacamten in obstructive hypertrophic cardiomyopathy: Observations from a tertiary care center.

BACKGROUND: In symptomatic obstructive hypertrophic cardiomyopathy (oHCM) patients, mavacamten is commercially approved to help improve left ventricular (LV) outflow tract (LVOT) gradients, symptoms, and reduce eligibility for septal reduction therapy (SRT) under the risk evaluation and mitigation strategy (REMS) program. We sought to prospectively report the initial real-world clinical experience with the use of commercially available mavacamten in a multi-hospital tertiary healthcare system. METHODS: We studied the first 150 consecutive oHCM patients (mean age 65 years, 53% women, 83% on betablockers and 61% in New York Heart Association [NYHA] class III) who were initiated on 5 mg of mavacamten with dose titrations using symptom assessment and echocardiographic measurements of LVOT gradient and LV ejection fraction (LVEF) measurements. We measured changes in NYHA class, LVEF, LVOT gradients (resting and Valsalva) at baseline, 4, 8 and 12 weeks. RESULTS: At 261 ± 143 days (range of 31-571 days), 69 (46%) patients had ≥1 NYHA class, and 27 (18%) additional patients had ≥2 NYHA class improvement. The mean Valsalva LVOT gradient decreased from 72 ± 43 mmHg at baseline to 29 ± 31 mmHg at 4 weeks, 29 ± 28 mmHg at 8 weeks and 30 ± 29 mmHg at 12 weeks (p < 0.001). At baseline, 100% patients had Valsalva LVOT gradients ≥30 mmHg, which reduced to 29% at 4 weeks, 28% at 8 weeks and 30% at 12 weeks. In 40 patients who reported no symptomatic improvement, the mean Valsalva LVOT gradient decreased from 73 ± 39 mmHg at baseline to 34 ± 27 mmHg at 4 weeks, 35 ± 28 mmHg at 8 weeks and 30 ± 24 mmHg at 12 weeks (P < 0.001). The mean LVEF at baseline was 66 ± 6% and changed to 64 ± 5% at 4 weeks, 63 ± 5% at 8 weeks and 62 ± 7% at 12 weeks (p < 0.0001). No patient underwent SRT, developed LVEF ≤30% or developed heart failure requiring admission. Three (2%) patients needed temporary interruption of mavacamten due to LVEF<50%. CONCLUSIONS: In a real-world study in symptomatic oHCM patients at a multi-hospital tertiary care referral center, we demonstrate the efficacy and safety, along with the logistic feasibility of prescribing mavacamten under the REMS program.

Hypertrophic cardiomyopathy: investigational drugs inhibiting myosin and upcoming agents.

INTRODUCTION: Hypertrophic cardiomyopathy (HCM), a phenotypically variable disorder with a genetic basis, was first described in the late 1800s. Since the discovery of the disease, various medical and surgical treatments have been proposed with surgical treatments proving to be of more benefit than medical in patients with severe symptoms. Although beta blockers, calcium channel blockers, and disopyramide have been used for their negative inotropic effect, the data behind utilization of these medications is weak at best. AREAS COVERED: Herein, we describe a first-in-man class of medications called cardiac myosin inhibitors (CMI), which have been recently approved by the Food and Drug Administration (FDA) for the treatment of symptomatic patients with obstructive HCM. PubMed was the primary database searched. EXPERT OPINION: Whether these medications will stand the test of time remains to be seen. They do appear to provide significant benefit and disease modification in early randomized trials with the drawback of decreasing contractility and ejection fraction. In our opinion, this new class of medications is an option for patients with NYHA class II-III symptoms from obstructive HCM who have EF ≥ 55%.

Upper Gastrointestinal Neoplasia and Worrisome Thyroid Nodules are Common in Colonic Polyposis of Unknown Etiology (CPUE).

BACKGROUND: Colonic polyposis of unknown etiology (CPUE) is defined as ≥10 cumulative colonic adenomas without a detectable germline pathogenic variant. Surveillance for patients with >100 adenomas is recommended, similar to patients with familial adenomatous polyposis. The utility of extra-colonic screening in patients with 10 to <100 adenomas is not well established. METHODS: All CPUE patients seen at our center between 2003 and 2022 were included. Patients were categorized based on the range of cumulative colorectal adenoma count: 10 to 19, 20 to 99, and ≥100. RESULTS: In all, 150 patients were identified of which 20(13.3%) had 10 to 19 cumulative adenomas, 79(52.7%) had 20 to 99 adenomas, and 51(34.0%) had ≥100 adenomas. Compared with patients with 10 to 19 and 20 to 99, patients with ≥100 adenomas were younger (mean 51 vs. 52 vs. 42 y, respectively). Of patients who underwent esophagogastroduodenoscopy, duodenal adenomas were found in 33.3%, 10.1%, and 38% in the 3 groups, respectively, P=0.002. Ampullary adenomas were significantly more common in the ≥100 adenoma group (14.8%, P=0.019) compared with 8.3% and 2.9% in the 10 to 19 and 20 to 99 groups, respectively. Thyroid nodules ≥1 cm were not detected in patients with 10 to 19 adenomas but were found in 23.3% and 14.3% of patients with 20 to 99 and ≥100 adenomas, respectively (P=0.254). CONCLUSION: In our cohort, duodenal and gastric adenomas occurred in CPUE patients with adenoma count 10 to ≥100 at a relatively high proportion. We recommend a baseline esophagogastroduodenoscopy in all patients with CPUE. While clinically significant thyroid nodules were not detected in patients with 10 to 19 adenomas, they occurred in about one-fifth of the patients with ≥20 adenomas, indicating that thyroid ultrasound is prudent.

Mavacamten, an Alternative to Septal Reduction Therapy for Patients with Hypertrophic Cardiomyopathy.

Hypertrophic cardiomyopathy (HCM) is a common heridetary cardiac disorder characterized by a wide range of symptoms. The pharmacological treatment of HCM is currently limited to beta blockers, non-dihydropyridine calcium channel blockers and disopyramide. Mavacamten is a novel cardiac myosin inhibitor, which was recently added to the limited pharmacological list of treatment options for HCM. This editorial elaborates on current evidence evaluating the use of mavacamten in patients with symptomatic obstructive HCM, comments on its current use and its expanded potential applications in the future.

Risk of Venous Thromboembolism in Multiple Myeloma Patients During the Immediate Peri-Autologous Hematopoietic Cell Transplantation Phase.

Venous thromboembolism (VTE) is a serious complication commonly experienced in cancer patients. Incidence of VTE typically brings poor prognosis as it represents the second most common cause of mortality in cancer patients just after the malignancy itself. Studies suggest that multiple myeloma (MM) is among the malignancies with further enhanced risk of VTE, especially in patients undergoing autologous hematopoietic cell transplantation (AHCT). However, risk factors and preventative approaches remain poorly explored. Here, we explore the incidence of VTE in MM patients undergoing AHCT, while also highlighting risk factors and preventions that may aid in preventing VTE in patients who are at higher risk.

High-grade large cell neuroendocrine carcinoma of the esophagus: a case report and review of the literature.

BACKGROUND: Neuroendocrine carcinomas are extremely rare in the esophagus as they represent less than 0.04% of all neuroendocrine tumors. To date, only 14 cases of poorly differentiated, high-grade esophageal NEC have been described in the literature. The majority of these patients presented with typical dysphagia symptoms. Due to its rarity, no standardized guidelines have been proposed to treat esophageal neuroendocrine carcinoma, although general recommendations suggest surgery with adjuvant chemoradiotherapy as the treatment of choice. CASE PRESENTATION: A 67-year-old previously healthy White male presented with a year-long intermittent nonspecific retrosternal discomfort, with the absence of any other symptoms. Esophagogastroduodenoscopy revealed an ulcerative mass in his lower esophagus, with concern of malignancy. Endoscopic ultrasound-guided biopsy revealed poorly differentiated neuroendocrine carcinoma of the esophagus with metastasis to a diaphragmatic lymph node. He was treated with neoadjuvant chemoradiation followed by surgery, and he has been in remission for over 5 years. CONCLUSION: Here, we review the literature and report a unique case of a patient with a vague presentation of esophageal neuroendocrine carcinoma as he enters his sixth year of survival following neoadjuvant chemoradiotherapy.

Prevalence of programmed death ligand-1 in patients diagnosed with non-small cell lung cancer in Lebanon.

INTRODUCTION: Programmed death ligand-1 expression has been shown to be a good predictor of response to cancer therapy with checkpoint inhibitors. Its expression varies among different tumor types and among non-small cell lung cancer patients with different clinical and demographic characteristics. The prevalence and determinants of programmed death ligand-1 expression have been previously reported from various regions of the world, but data from Lebanon are lacking. This study examines the prevalence and the clinical, demographic and pathological predictors of programmed death ligand-1 expression in patients diagnosed with non-small cell lung cancer in Lebanon. METHODS: Medical records of 180 patients diagnosed with primary non-small cell lung cancer at our institution and tested for programmed death ligand-1 expression were reviewed. Clinical, demographic and pathological information were collected and correlated with programmed death ligand-1 expression using the chi-square test and logistic regression. RESULTS: One hundred eleven of the 180 non-small cell lung cancer tumor samples tested positive for programmed death ligand-1 expression (61.7%). 27.2% of those tumor samples expressed programmed death ligand-1 in 1%-49% of tumor cells, while 34.4% of tumor samples expressed programmed death ligand-1 in 50% or more of their cells. Squamous histology and advanced stage were significant predictors of programmed death ligand-1 expression (odds ratio = 2.79, 95% confidence interval [1.13-6.90], p = 0.012 and odds ratio = 2.48, 95% confidence interval [1.23-4.99], p = 0.044, respectively). CONCLUSION: Similar to reports from other populations, our results suggest that programmed death ligand-1 expression in non-small cell lung cancer is highly prevalent in the Lebanese population, especially in patients with advanced stage at diagnosis or squamous cell carcinoma histology. Because of the small sample size, while more that 60% of the patients are Lebanese, the results of this article cannot be extrapolated to the Middle Eastern and the Levantine population.

Severe acute respiratory syndrome coronavirus 2 reinfection in a coronavirus disease 2019 recovered young adult: a case report.

BACKGROUND: Coronavirus disease 2019 has been a public health threat and a worldwide emergency for more than a year. Unfortunately, many questions concerning the pathophysiology, management, and long-term side effects remain unanswered, and novel aspects of the disease keep on emerging. Of concern to healthcare providers are the recent reported cases of reinfection. Serum coronavirus disease 2019 antibodies have been detected within a few days after onset of the disease. However, it remains unclear whether this immune response is universal, or whether it can lead to latent immunity. CASE PRESENTATION: A previously healthy 27-year-old white man presented with fever, chills, back pain, and other constitutional symptoms, 2 days after being exposed to coronavirus disease 2019 positive patients. His severe acute respiratory syndrome coronavirus 2 polymerase chain reaction was positive, and his symptoms resolved over the next 2 weeks. One month after a confirmatory negative severe acute respiratory syndrome coronavirus 2 polymerase chain reaction, he was found to be ineligible for plasma donation as his anti-severe acute respiratory syndrome coronavirus 2 serology was negative. The patient redeveloped symptoms similar to his first infection 3 weeks after the negative serology test. He and his wife both tested positive via polymerase chain reaction. Their symptoms resolved over the next few days, and they had a negative polymerase chain reaction test 10 days after the positive polymerase chain reaction. CONCLUSION: While studies showed that anti-severe acute respiratory syndrome coronavirus 2 immunoglobulins start to develop early after infection, our healthy young patient's immune system failed to mount latent immunity against the virus. This left him, especially amid widespread social and medical misconceptions, vulnerable to reinfection by severe acute respiratory syndrome coronavirus 2. Our case disputes the timelines for immune response that were set and supported by research studies. Our case also raises questions regarding prioritizing vaccinating other individuals over those with prior infection.

Fibroscan and low-density lipoprotein as determinants of severe liver fibrosis in diabetic patients with nonalcoholic fatty liver disease.

BACKGROUND: Fibroscan is an effective and noninvasive tool to quantify fibrosis and steatosis in liver diseases including nonalcoholic fatty liver disease (NAFLD). Type-2-diabetes is a known risk factor for worse prognosis in NAFLD. In this study, we compare liver status in NAFDL diabetic and nondiabetic patients, identify potential risk factors, and determine the usefulness of Fibroscan in this population. PATIENTS AND METHODS: The charts of all patients with NAFLD who underwent Fibroscan at our institution were reviewed. Fibroscan results, demographics, and clinical data were collected and analyzed using SPSS software. RESULTS: Of the 248 NAFLD patients, 73 (29.4%) were diabetic and 175 (70.6%) were nondiabetic. As detected by the NAFLD' liver stiffness measure, 35 (47.94%) diabetic patients had severe liver fibrosis (F4) in contrast to only 46 (26.3%) nondiabetics. Diabetic patients also presented more with hypertension, dyslipidemia, coronary artery disease, and chronic kidney disease. Liver steatosis, liver function tests, and noninvasive scores did not vary significantly between the two groups, except for γ-glutamyltransferase, prothrombin time-international normalized ratio, and BMI-alanine aminotransferase ratio-diabetes score. Diabetic patients had significantly lower high-density lipoproteins and low-density lipoproteins. CONCLUSION: Fibroscan results and low-density lipoprotein are potential diagnostic factors of liver fibrosis in diabetic patients with NAFLD. Further studies are necessary to verify liver fibrosis diagnostic tools and prognostic and genetic markers in diabetic patients.