Objective: Unusual clinical course Background: "Bath salts" is the street name for a group of recently identified and increasingly abused stimulant synthetic cathinones that are associated with multiple systemic effects. We present a case of a patient who developed reversible dilated cardiomyopathy secondary to their use. Case Report: A 27 year old male with no past medical history was brought to emergency department with agitation. He had been inhaling and intravenously injecting "bath salts", containing a mephedrone/Methylenedioxypyrovalerone (MDPV) combination. On presentation, he was tachycardic, hypotensive and febrile. His initial labs showed an elevated white count, creatinine and creatinine phosphokinase levels. His erythrocyte sedimentation rate; C-reactive protein; urinalysis; urine drug screen; Human Immunodeficiency Virus, hepatitis, coxsackie, and influenza serology were normal. EKG showed sinus tachycardia. An echocardiogram was done which showed dilated cardiomyopathy with an ejection fraction (EF) of 15-20% and global hypokinesia. A left heart catheterization was done and was negative for coronary artery disease. At a 20 week follow up, he had stopped abusing bath salts and was asymptomatic. A repeat echocardiogram showed an EF of 52%. Cocnlusions: Bath salts (MDPV, mephedrone) are synthetic cathinones with amphetamine/cocaine like properties with potential cardiotoxic effects. Cardiovascular manifestations reported include tachycardia, hypertension, myocardial infarction, arrhythmias and cardiac arrest. "Bath salts" can also cause severe reversible dilated cardiomyopathy. Prior to diagnosis, other causes of cardiomyopathy including ischemic, infectious, familial, immunological, metabolic and cytotoxic may need to be ruled out; as was done in our patient.

Background: Chemotherapeutic agents directed against human epidermal growth factor receptor 2 (HER-2) have significantly improved the prognosis of patients who are positive for this receptor. However, cardiomyopathy remains as a common adverse effect of using these agents. Materials and Methods: Literature search was conducted via PubMed using the keywords of "Trastuzumab Cardiomyopathy," "Lapatinib Cardiomyopathy" and "Pertuzumab Cardiomyopathy," which provided 104 results. These articles were then screened for relevance to the targeted subject based on their title and abstracts. Case reports and articles that were not discussing any aspect of cardiomyopathy secondary to targeted therapy for breast cancer and articles not in English were eliminated. After elimination, a bibliography search among selected articles was done and a total of 46 articles were identified. The collected articles were then meticulously analyzed and summarized. Results: The use of human epidermal growth factor receptor 2 (HER-2) receptor targeted chemotherapy in breast cancer is limited because of a higher incidence (19-22%) of cardiomyopathy. The incidence of cardiomyopathy is not dose dependent and in most cases it is reversible after discontinuation of the drug and treatment with heart failure medications. Severe adverse outcomes including death or permanent disability are rare. Conclusion: HER-2 targeted chemotherapy for breast cancer has a higher incidence of associated reversible cardiomyopathy. Patients should be monitored by serial echocardiography starting at the beginning of the treatment and followed by every 3 months until the completion of chemotherapy. Co-ordination between oncologists and cardiologists is needed to develop evidence-based protocols to prevent, identify, monitor and treat trastuzumab-induced cardiomyopathy.

Cardiovascular disease in populations with obesity is a major concern because of its epidemic proportion. Obesity leads to the development of cardiomyopathy directly via inflammatory mediators and indirectly by obesity-induced hypertension, diabetes and coronary artery diseases. The aim of this review article is to re-visit the available knowledge and the evidence on pathophysiologic mechanisms of obesity-related cardiomyopathy and to propose its placement into a specific category of myocardial disease.

Oxidative stress plays an important role in cardiac diseases, which has been well demonstrated, whereas the role of reductive stress has been poorly investigated. We and others have shown previously that heat shock protein 27 (Hsp27) plays a role as an antioxidant. To investigate whether overexpression of Hsp27 could lead to reductive stress and result in cardiomyopathy, we generated transgenic mice with different expression levels of Hsp27. We observed that transgenic mice with high levels of Hsp27 developed cardiomyopathy. The myopathic hearts were under reductive stress, which was evidenced by an increased ratio of reduced glutathione/oxidized glutathione and a decreased level of reactive oxygen species. In addition, upregulated glutathione peroxidase 1 and decreased iron content were revealed in the myopathic hearts. More importantly, inhibition of glutathione peroxidase 1 significantly attenuated the development of cardiomyopathy. The data indicate that the Hsp27-induced cardiomyopathy could be attributed to, at least in part, upregulation of glutathione peroxidase 1. Our findings suggest that reductive stress plays an important role in the development of cardiomyopathy and that Hsp27 may serve as a potential target for the treatment of patients with cardiomyopathy.

Myeloid differentiation protein-88 (MyD88) is a crucial adaptor protein in the innate immune response. A protective role for MyD88 in normal cardiac function has been proposed in a surgical hypertrophic model. To assess the in vivo role of MyD88 in cardiac remodeling, we generated transgenic mice with cardiac-restricted expression of a dominant negative mutant of MyD88 (dnMyD88). Surprisingly, dnMyD88 transgenic mice displayed characteristic features of heart failure; including heart weight increase, cardiomyocytes enlargement, interstitial fibrosis, and re-expression of "fetal" genes. Echocardiographic examination of dnMyD88 hearts revealed dilated chamber volume and reduced cardiac contractility. DnMyD88 mice died from heart failure before they were 7 months old, as shown by Kaplan-Meier analysis. Additionally, the heart failure phenotype of dnMyD88 mice was associated with abnormal activation of the Akt/GSK-3β signaling pathway. These data provide the first evidence that normal MyD88 signaling is crucial for maintaining the physiological function of the adult heart.

Introduction: Hypertrophic cardiomyopathy (HCM) is a heterogeneous disorder of the cardiac sarcomere, resulting in myocyte hypertrophy and disarray, interstitial fibrosis, and cardiac dysfunction. Our aim was to determine whether the amount of fibrosis in HCM correlates with echocardiographic measures of diastolic dysfunction, presence of HCM-susceptibility mutations, or polymorphisms in the renin-angiotensin-aldosterone system (RAAS). Methods: Surgical specimens from patients with obstructive HCM undergoing septal myectomy at the Mayo Clinic (2001-2004) were examined and compared with autopsy-derived tissues from age- and sex-matched normal controls. Digital image analysis was used to quantitate the fibrosis in representative microscopic sections. Genotyping was performed for myofilament-HCM using polymerase chain reaction, high-performance liquid chromatography, and direct DNA sequencing. RAAS polymorphism status was similarly established. Results: The study included 59 HCM cases and 44 controls. Patients with HCM exhibited more fibrosis (mean 17%, range 3-45%) than controls (mean 8%, range 3-17%) (P<.0001). A significant relationship existed between amount of fibrosis and maximum wall thickness (P=.02), left ventricular ejection fraction (P=.02), and peak early/late diastolic mitral annulus velocity (E/A ratio) (P=.002). Although there was no association between amount of fibrosis and myofilament-HCM genotype status or polymorphisms in the RAAS cascade, there was a trend toward more fibrosis in patients with ≥1 C-encoding allele in CYP11B2-encoded aldosterone synthase. Conclusions: Patients with HCM undergoing septal myectomy had significantly more myocardial interstitial fibrosis than controls. The amount of fibrosis in HCM patients correlated with degree of septal hypertrophy and left ventricular systolic and diastolic function. Notably, neither mutations in cardiac myofilament proteins or polymorphisms in RAAS exhibited strong associations with severity of myocardial fibrosis.

Claudin-5 is a transmembrane cell junction protein that is a component of tight junctions in endothelial cell layers. We have previously shown that claudin-5 also localizes to lateral membranes of murine cardiomyocytes at their junction with the extracellular matrix. Claudin-5 levels are specifically reduced in myocytes from a mouse model of muscular dystrophy with cardiomyopathy. To establish whether claudin-5 is similarly specifically reduced in human cardiomyopathy, we compared the levels of claudin-5 with other cell junction proteins in 62 cardiomyopathic end-stage explant samples. We show that claudin-5 levels are reduced in at least 60% of patient samples compared with non-failing controls. Importantly, claudin-5 reductions can be independent of connexin-43, a gap junction protein previously reported to be reduced in failing heart samples. Other cell junction proteins including α-catenin, β-catenin, γ-catenin, desmoplakin, and N-cadherin are reduced in only a small number of failing samples and only in combination with reduced claudin-5 or connexin-43 levels. We also show that reduced claudin-5 levels can be present independently from dystrophin alterations, which are known to be capable of causing and resulting from cardiomyopathy. These data are the first to show alterations of a tight junction protein in human cardiomyopathy samples and suggest that claudin-5 may participate in novel mechanisms in the pathway to end-stage heart failure.

Background. Cardiac dysfunction is present in >40% of sepsis patients and is associated with mortality rates of up to 70%. Recent evidence suggests that glycolytic metabolism plays a critical role in host defense and inflammation. Activation of Toll-like receptors on immune cells can enhance glycolytic metabolism. This study investigated whether modulation of glycolysis by inhibition of hexokinase will be beneficial to septic cardiomyopathy. Methods. Male C57B6/J mice were treated with a hexokinase inhibitor (2-deoxy-d-glucose [2-DG], 0.25-2 g/kg, n = 6-8) before cecal ligation and puncture (CLP) induced sepsis. Untreated septic mice served as control. Sham surgically operated mice treated with or without the 2-DG inhibitor served as sham controls. Cardiac function was assessed 6 hours after CLP sepsis by echocardiography. Serum was harvested for measurement of inflammatory cytokines and lactate. Results. Sepsis-induced cardiac dysfunction was significantly attenuated by administration of 2-DG. Ejection fraction and fractional shortening in 2-DG-treated septic mice were significantly (P < .05) greater than in untreated CLP mice. 2-DG administration also significantly improved survival outcome, reduced kidney and liver injury, attenuated sepsis-increased serum levels of tumor necrosis factor α and interleukin 1β as well as lactate, and enhanced the expression of Sirt1 and Sirt3 in the myocardium, which play an important role in mitochondrial function and metabolism. In addition, 2-DG administration suppresses sepsis-increased expression of apoptotic inducers Bak and Bax as well as JNK phosphorylation in the myocardium. Conclusions. Glycolytic metabolism plays an important role in mediating sepsis-induced septic cardiomyopathy. The mechanisms may involve regulation of inflammatory response and apoptotic signaling.

Amyloidosis involves extracellular deposition of abnormal proteins/fibrils with potential end organ damage. AL type amyloidosis is one subtype and a clonal plasma cell disorder. A 74-year-old completely asymptomatic male presented with progressive renal dysfunction. Work up with serum protein electrophoresis (SPEP) and immunofixation revealed monoclonal IgG Lamda spike of 1.1 g/dL. Urine protein electrophoresis noted Bence Jones proteins. Notable labs, hemoglobin 10.6 g/dL, calcium was 8.2 mg/dL, and creatinine 2.4 mg/dL. Quantitative immunoglobulins IgA, IgG, and IgM, were 59 mg/dL, 1,939 mg/dL, and 23 mg/dL, respectively. Lambda and Kappa free light chains 26.37 mg/L and 127.87 mg/L, respectively, with a ratio of 0.21. Skeletal survey noted a 4 mm lucency of the left frontal bone. Bone marrow biopsy confirmed 21% plasma cells. Renal biopsy revealed AL lambda light chain confirming final diagnosis AL Lambda light chain Amyloidosis and IgG Lambda Multiple Myeloma. Treatment with daratumumab, cyclophosphamide, bortezomib, and dexamethasone initiated. His clinical course was complicated by COVID 19 infection prior to treatment initiation and with congestive heart failure secondary to cardiac amyloidosis (elevated Troponin and Brain Natriuretic Peptide level) during induction therapy requiring hospitalization, diuresis and optimization of cardiac medications. Very Good Partial Response (VGPR) noted after 2 cycles and near Complete Response (CR) after 4 cycles. Patient was evaluated and approved for Stem cell transplant (SCT) but decided against SCT and has now proceeded to single agent daratumumab maintenance. Amyloidosis is an uncommon disease seen in older adults (median age 64) with deposition of fibrils composed of low molecular weight subunits derived from normal proteins. Various subtypes and protien/fibrils include AL amyloidosis (immunoglobulin light chain), hereditary/ familial transthyretin amyloidosis (mutated transthyretin, apolipoprotien, fibrinogen A, lysozyme), wildtype transthyretin Amyoidosis/senile amyloidosis (unmutated transthyretin) and AA amyloidosis (serum amyloid A fibril). AL amyloidosis is a systemic disorder that presents with nephrotic syndrome or restrictive cardiomyopathy (as in this case). Other presentations involve peripheral neuropathy, hepatomegaly, macroglossia, arthropathy with “shoulder pad” sign, bleeding diathesis, purpura including “racoon eyes”. Biopsy of the affected organ (kidney, liver, fat pad aspirate, bone marrow) with Congo red staining confirms the histologic diagnosis. Amyloid light chains can be confirmed with proteomic analysis (mass spectrometry or immuno-electron-microscopy). AL amyloidosis treatment entails high dose chemotherapy and autologous SCT. Long term prognosis in advanced stage is poor. Survival can be short (4-6 months), heart failure causing about 50% of deaths. Daratumumab-regimens offer a 40-55% CR and with SCT data (83% five year and 50% ten-year survival) the outlook is improving.

Hyper eosinophilia with cardiomyopathy as manifestation of Churg Strauss syndrome Hakam Khazrik MD1, Purva Sharma MD1 Division of Hematology/Oncology, Dept of Internal Medicine, East Tennessee State University. Eosinophilia (≥500 eosinophils/micro-L) and hyper eosinophilia (≥1500 eosinophils/micro-L) could be caused by many conditions including allergic, infectious, inflammatory and neoplastic disorders. Patient may present with severe organ involvement require hospitalization and urgent intervention. A 39-year-old female with history of asthma, nasal polyps presented with worsening dyspnea, lower extremity edema, acute left heart failure and non-ST elevation myocardial infarction with significant troponin elevation (31 ng/ml). Cardiac catheterization revealed no stenosis, echocardiogram showed severely reduced ejection fraction 20%. She was managed medically with presumptive diagnosis of viral myocarditis. One month later she represented with similar symptoms associated with mild facial malar rash and worsening peripheral eosinophilia (absolute count 6400cells/micro-L), leukocytosis (WBC 11k/ul norma differential except eosinophilia mild anemia Hg: 10g/dl, normal platelet(304k/ul), normal renal and liver functions, mild elevated tryptase 16. CT chest revealed bilateral hilar lymphadenopathy with no pulmonary infiltrate. Parasite, fungal,, tuberculosis, HIV, hepatitis infections were ruled out. Bone marrow biopsy revealed hypercellular marrow for age, mild increased marrow eosinophilic precursor, normal cytogenetics, FISH studies for MDS, eosinophilia, and BCR-ABL as well as molecular MPN panel were unremarkable. No lymphoproliferative disorder or increased blasts noted. Subcarinal lymph node biopsy with normal lymph node tissue. Extensive rheumatological workup was unremarkable except for elevated rheumatoid factor, ESR, CRP, anti-myeloperoxidase and anti-protease- 3. Eosinophilic granulomatosis with polyangiitis, (EGPA)was diagnosed. Patient started on long taper prednisone with improvement in her symptoms and her eosinophilia. Given severe disease with cardiac involvement she was started on cyclophosphamide to improve her prognosis. Eosinophilic granulomatosis with polyangiitis (Churg-Strauss), is multisystem disorder characterized by chronic rhinosinusitis, asthma and prominent peripheral blood eosinophilia. Asthma is the cardinal feature. Skin and neurological involvement is usually common but cardiac involvement is one of the more serious manifestations of EGPA accounting for approximately one-half of deaths attributable to EGPA. Two sets of diagnostic criteria are commonly used: the American College of Rheumatology (ACR) criteria and the Lanham criteria. Main diseases to consider in the differential diagnosis of EGPA are aspirin-exacerbated respiratory disease, the eosinophilic pneumonias, allergic bronchopulmonary aspergillosis, hyper eosinophilic syndrome, granulomatosis with polyangiitis and microscopic polyangiitis.