Diabetes causes cardiomyopathy and increases the risk of heart failure independent of hypertension and coronary heart disease. This condition called “Diabetic Cardiomyopathy” (DCM) is becoming a well- known clinical entity. Recently, there has been substantial research exploring its molecular mechanisms, structural and functional changes, and possible development of therapeutic approaches for the prevention and treatment of DCM. This review summarizes the recent advancements to better understand fundamental molecular abnormalities that promote this cardiomyopathy and novel therapies for future research. Additionally, different diagnostic modalities, up to date screening tests to guide clinicians with early diagnosis and available current treatment options has been outlined.

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A left ventricular assist device is a mechanical pump implanted in patients with heart failure that continuously takes blood from the left ventricle and delivers it to the aorta, thus decreasing ventricular load. The device is typically considered as a ‘bridge to transplant’, i.e. as a temporary therapy, and involves several risks. Modified ventricular hemodynamics due to a heart pump implantation is studied in-vitro using an elastic ventricle. The ventricle is incorporated into a pulse duplicator setup, which prescribes realistic pulsatile inflow/outflow to mimic a weak ejection fraction. A continuous axial pump mimics a ventricular assist device and its effect on the ventricular hemodynamics is investigated as a function of the pump flow suction. Using particle image velocimetry, pump flow effectiveness at providing unloading on the ventricle and increasing ejection is observed and understanding if proper recirculation of the myocardium down to the apex is restored under varying flow rate.

Introduction: Peripartum Cardiomyopathy (PPCM) affects 1 in 3,000 pregnancies and accounts for 5% of heart transplants in US women. Preeclampsia is one of the Hypertensive Disorders of Pregnancy (HDOP) that has been epidemiologically associated with PPCM which is a form of dilated cardiomyopathy. This concurrent clinical presentation of PPCM with associated Preeclampsia appears to be increasing in rural Northeast Tennessee. The diagnosis of Peripartum Cardiomyopathy is made by echocardiographic criteria of left ventricular dysfunction with LVEF Case Presentation: A 22 year old G2P0010 @ 33 weeks and 1 day gestation was accepted as a transfer of care from an outside hospital. Patient had no prenatal care, was homeless, had a history of depression and polysubstance abuse. She presented with abdominal pain, shortness of breath, coughing, and unknown due date. Vitals on presentation were BP 175/99 mmHg, HR 113, respiratory rate 32, and temperature 99.2. Lab results showed elevated AST/ALT 234/102, LDH 903, Uric Acid 7.0, WBC 26.2, and BNP 1935. The 24 hour urine total protein resulted 4455 mg. Transthoracic echocardiogram revealed LV ejection fraction of 30 to 35% with global hypokinesis of the LV wall. The CXR was consistent with bilateral infiltrates and pulmonary edema. She was admitted to L & D and given a dose of Betamethasone for fetal lung maturity. Fetal heart tracing showed a baseline of 145 bpm with minimal variability and no accelerations or decelerations. The tocodynamometer showed contractions q 3-5 minutes and the ultrasound evaluation showed cephalic presentation. Social work and Cardiology consults were obtained. The clinical diagnoses of Peripartum Cardiomyopathy, Preeclampsia with severe features, and Bilateral Pneumonia were made and treatment included Lasix, Metoprolol, Magnesium Sulfate, Ceftriaxone, and Azithromycin. A primary low transverse cesarean delivery was performed with a live female infant weighing 1920 grams, 4 pounds 4 ounces, and Apgars: 6, 8. The patient was discharged home on Metoprolol XL 25 mg bid, Lisinopril 10 mg daily, Procardia 30 mg daily, Lovenox 40 mg daily, and Depo-Provera for contraception. Patient was informed that she would need a repeat echocardiogram in 3 months to assess left ventricular function. Discussion: In this Appalachian region, there is an increased occurrence of Peripartum Cardiomyopathy presenting concurrently with Preeclampsia. These two combined clinical entities increase maternal morbidity and mortality. From a public health perspective, this clinical case highlights the psychosocial factors such as poverty, homelessness, polysubstance abuse, and depression that may have contributed to the clinical disease. The distinct features of this preterm antepartum case of PPCM are a younger, Caucasian primigravida with singleton gestation. Healthcare providers should have heightened awareness of this clinical presentation, especially in the postpartum period.

Type 2 diabetes and cigarette smoke exposure are associated with an increased risk of cardiovascular complications. The role of advanced glycation end-products (AGEs) is already well-established in numerous comorbidities including cardiomyopathy. Given the role of AGEs and their receptor, RAGE, in activating inflammatory pathways, we sought to determine whether ceramides could be a mediator of RAGE-induced altered heart mitochondrial function. Using an in vitro model, we treated H9C2 cardiomyocytes with carboxy-methyl lysine-BSA, followed by mitochondrial respiration assessment. We found that mitochondrial respiration was significantly impaired in AGE-treated cells, but not when co-treated with myriocin, an inhibitor of de novo ceramide biosynthesis. Moreover, we exposed WT and RAGE KO mice to side-stream cigarette smoke and found reduced mitochondrial respiration in the left ventricle myocardium from WT mice, but the RAGE KO mice were protected from this effect. Finally, conditional over-expression of RAGE in the lungs of mice also elicited a robust increase in left ventricular ceramides. Altogether, these findings suggest a RAGE-ceramide axis as an important contributor to cardiomyopathy.

Methamphetamine abuse is a growing global health concern. Cardiovascular disease is the leading cause of death in methamphetamine users because of its significant effects on vasoconstriction, pulmonary hypertension, atherosclerotic plaque formation, cardiac arrhythmias, and cardiomyopathy. Stimulants like methamphetamine and cocaine are known to induce severe coronary vasospasm resulting in angina and myocardial infarction (MI), but MI secondary to methamphetamine-induced coronary thrombosis is rarely reported. A 40-year-old female with medical history of immune thrombocytopenia s/p splenectomy, NSTEMI, tobacco and substance abuse presented to the hospital via EMS in an unresponsive state. Patient was admitted to the hospital 20 days before the current episode with complaints of chest pain and was diagnosed with NSTEMI due to troponin elevation without EKG changes; Echocardiogram at that time showed a left ventricular ejection fraction (LVEF) of 55-60% without any other abnormalities. Coronary angiography at that time was unremarkable except for mild luminal irregularities of the left anterior descending (LAD) artery. The patient’s symptoms resolved and was discharged home with a diagnosis of COVID-induced MI with nonobstructive coronaries. During the current episode, the patient started having crushing substernal chest pain radiating to left shoulder and associated with dizziness. She suffered cardiac arrest on the way to the hospital but was successfully resuscitated. EKG revealed anterior STEMI and the patient was loaded with aspirin. Emergent coronary angiography showed 100% occlusion of proximal LAD, while other coronaries were completely patent without any atherosclerotic plaque. A successful mechanical thrombectomy followed by a 4 x 28 mm drug-eluting stent was placed in the ostial-proximal LAD. TIMI-3 flow was restored and post-intervention troponin peaked at 70. Urine drug screen was positive for amphetamines and benzodiazepines. The echocardiogram showed a reduced LVEF of 30%. Patient was started on dual antiplatelet therapy with aspirin and ticagrelor, rosuvastatin, and low-dose metoprolol tartrate; further guideline-directed medical therapy could not be initiated due to patient’s low blood pressure. Hypercoagulability workup was negative for any abnormalities. As other usual causes were ruled out, the patient was deemed to have methamphetamine-induced coronary thrombosis resulting in myocardial infarction, and cardiomyopathy. Discussion Amphetamines are potent sympathomimetic agents that increase the risk of MI through various cardiovascular effects. Elevated serum catecholamines lead to increased heart rate, and blood pressure resulting in increased myocardial oxygen demand, while also inducing coronary vasospasm which can limit myocardial oxygen supply. Furthermore, in-vitro studies have shown amphetamines are prothrombotic as they can induce tissue factor (TF) expression, activate endothelial cells, and inhibit the activity of tissue factor pathway inhibitor (TFPI). They also increase the expression of plasminogen activator inhibitor-1 (PAI-1), a key fibrinolysis suppressant. In contrast to cocaine, amphetamines can induce thrombosis even in a non-inflamed endothelium, affecting even young individuals without atherosclerotic risk factors. These cumulative procoagulant effects may result in coronary artery thrombi as seen in our patient, which combined with other adrenergic effects, poses a significant risk for acute coronary events.

Coronavirus disease 2019 (COVID-19), which is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has emerged as a global pandemic with an unprecedented death toll worldwide. Although it primarily affects the respiratory tract presenting as pneumonia or acute respiratory failure, it is also known to cause significant cardiovascular complications, including acute coronary syndrome (ACS), arrhythmia, myopericarditis, cardiomyopathy, venous thromboembolism, heart failure, and cardiogenic shock. Morbidity and mortality secondary to cardiovascular complications are higher in patients with preexisting cardiovascular risk factors. Here, we present a case report of a 69-year-old male who was recently diagnosed with COVID-19 illness presenting with ST-elevation myocardial infarction (STEMI) and eventually with Takotsubo cardiomyopathy (TTC), and the course was complicated by right atrial thrombus and a pulmonary embolism (PE).

Hypertrophic cardiomyopathy (HCM) is the most common monogenic disorder and the leading cause of sudden arrhythmic death in children and young adults. It is typically asymptomatic and first manifests itself during cardiac arrest, making it a challenge to diagnose in advance. Computational models can explore and reveal underlying molecular mechanisms in cardiac electrophysiology by allowing researchers to alter various parameters such as tissue size or ionic current amplitudes. The goal of this thesis is to develop a computational model in MATLAB and to determine if this model can accurately indicate cases of hypertrophic cardiomyopathy. This goal is achieved by combining a three-dimensional network of the bidomain model with the Beeler-Reuter model and then by manually varying the thickness of that tissue and recording the resulting membrane potential with respect to time. The results of this analysis demonstrated that the developed model is able to depict variations in tissue thickness through the difference in membrane potential recordings. A one-way ANOVA analysis confirmed that the membrane potential recordings of the different thicknesses were significantly different from one another. This study assumed continuum behavior, which may not be indicative of diseased tissue. In the future, such a model might be validated through in vitro experiments that measure electrical activity in hypertrophied cardiac tissue. This model may be useful in future applications to study the ionic mechanisms related to hypertrophic cardiomyopathy or other related cardiac diseases.

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