Jagadeesh K. Kalavakunta

Cholesterol crystal induced arterial inflammation and destabilization of atherosclerotic plaque

Evolution of plaque that is prone to rupture is characterized by inflammation and physical changes. Accumulation of low-density lipoprotein in the sub-intima provides esterified cholesterol (ESC) to macrophages and smooth muscle cells that convert it into free cholesterol (FRC) by cholesteryl ester hydrolases (CEHs). Membrane-bound cholesterol carriers transport FRC to high-density lipoprotein (HDL). Impaired HDL transport function and altered composition can lead to extracellular accumulation of FRC, whereas impaired membrane carrier activity can lead to intracellular FRC accumulation. Saturation of FRC can result in cholesterol crystallization with cell death and intimal injury. Disequilibrium between ESC and FRC can impact foam cell and cholesterol crystal (CC) formation. Cholesterol crystals initiate inflammation via NLRP3 inflammasome leading to interleukin-1β (IL-1β) production inducing C-reactive protein. Eventually, crystals growing from within the plaque and associated inflammation destabilize the plaque. Thus, inhibition of inflammation by antagonists to IL-1β or agents that dissolve or prevent CC formation may stabilize vulnerable plaques.

Surviving sudden cardiac death secondary to anomalous left coronary artery from the pulmonary artery: A case report and literature review

Anomalous origin of the left coronary artery from the pulmonary artery (ALCAPA) is an uncommon type of congenital coronary anomaly. In adults, the clinical picture of ALCAPA varies widely between being asymptomatic, presenting similarly to other heart diseases, or as malignant arrhythmias. Patients who have cardiac arrest are usually young and do not exhibit prior warning symptoms. In this article we describe a case of a 22-year-old healthy male, who experienced cardiac arrest during exertion. He was then diagnosed with ALCAPA, which was surgically corrected.

Left ventricular noncompaction and myocardial fibrosis: a case report

Background Left ventricular noncompaction (LVNC) is a rare congenital abnormality. It is currently classified as a genetic cardiomyopathy and results from early arrest of endomyocardial morphogenesis. The pathophysiology of left ventricular dysfunction, which becomes apparent beyond the 4th decade of life, is unclear. Case report We report a case of 60-year-old woman who presented with shortness of breath and showed noncompacted endocardium on echocardiography. Cardiac catheterization and viral studies were unremarkable. Histology revealed endomyocardial fibrosis without disarray. She was subsequently diagnosed with LVNC and treated with medications. Discussion Cardiologists and other physicians should be aware of LVNC due to its high likelihood of misdiagnosis and associated high complication rates. Early diagnosis, intervention and screening among family members can decrease the morbidity and mortality associated with LVNC.

Frequency of Cholesterol Crystals in Culprit Coronary Artery Aspirate During Acute Myocardial Infarction and Their Relation to Inflammation and Myocardial Injury

Cholesterol crystals (CCs) have been associated with plaque rupture through mechanical injury and inflammation. This study evaluated the presence of CCs during acute myocardial infarction (AMI) and associated myocardial injury, inflammation, and arterial blood flow before and after percutaneous coronary intervention. Patients presenting with AMI (n = 286) had aspiration of culprit coronary artery obstruction. Aspirates were evaluated for crystal content, size, composition, and morphology by scanning electron microscopy, crystallography, and infrared spectroscopy. These were correlated with inflammatory biomarkers, cardiac enzymes, % coronary stenosis, and Thrombolysis in Myocardial Infarction (TIMI) blush and flow grades. Crystals were detected in 254 patients (89%) and confirmed to be cholesterol by spectroscopy. Of 286 patients 240 (84%) had CCs compacted into clusters that were large enough to be measured and analyzed. Moderate to extensive CC content was present in 172 cases (60%). Totally occluded arteries had significantly larger CC clusters than partially occluded arteries (p <0.05). Patients with CC cluster area >12,000 µm2 had significantly elevated interleukin-1 beta (IL-1β) levels (p <0.01), were less likely to have TIMI blush grade of 3 (p <0.01), and more likely to have TIMI flow grade of 1 (p <0.01). Patients with recurrent AMI had smaller CC cluster area (p <0.04), lower troponin (p <0.02), and IL-1β levels (p <0.04). Women had smaller CC clusters (p <0.04). Macrophages in the aspirates were found to be attached to CCs. Coronary artery aspirates had extensive deposits of CCs during AMI. In conclusion, presence of large CC clusters was associated with increased inflammation (IL-1β), increased arterial narrowing, and diminished reflow following percutaneous coronary intervention.

Demographic parameters related to 30-day readmission of patients with acute myocardial infarction: Analysis of 2,371,867 hospitalizations☆

BACKGROUND Acute myocardial infarction (AMI) is the most common cause of mortality in the USA as per the data released by the CDC. Short term hospital readmissions account for a significant portion of health care budget and much of the focus recently has been on reducing 30day readmission rate aimed to identify the demographics associated with readmissions from AMI and major causes of readmissions. METHODS We queried the Nationwide Inpatient Sample which represents 20% of all the United States hospital data for our study. AMI was identified through ICD9 Clinical Classification Software Code 100 for readmissions secondary to AMI for years 2009-2013. Chi-square was used for statistical analysis. RESULTS A total of 2,371,867 admissions were identified with AMI and 15.87% of these readmitted within 30days after index hospitalizations due to any cause. Patients with age greater than 65years, female gender, Medicare and Medicaid insurances, low median income for zip code and metropolitan areas were associated with high 30day readmission rate. The most common identified cause of readmission from 2009-2011 was coronary atherosclerosis (15%) and from 2012-2013 the cause identified was congestive heart failure (13.5%) (p<0.001). CONCLUSION Aggressive medical management needs to be targeted at this demography of patients and prevent the most causes of readmissions to reduce the cost and morbidity of patients admitted with AMI.

An unusual complication of polyarteritis nodosa with massive retroperitoneal hemorrhage: a case report

Background and Case report Polyarteritis Nodosa (PAN) is a systemic necrotizing vasculitis that affects medium-sized and occasionally involves small arteries leading to the disruption of the internal and external elastic lamina and contribute to the development of aneurysms. Aneurysms develop at bifurcation of major blood vessels; they are prone to thrombosis, rupture and haemorrhage. Retroperitoneal haemorrhage around kidneys was previously reported in patients with PAN. We report a case of massive retroperitoneal bleeding from inferior pancreaticoduodenal artery aneurysm rupture in a 70-year-old female with PAN. Conclusion Prognosis of untreated PAN is very poor with 20% 5 year survival rate, therefore early recognition of the disease will prevent catastrophic complications and improves survival.

Cholesterol crystal embolization following plaque rupture: a systemic disease with unusual features

Cholesterol crystal embolic (CCE) syndrome is often a clinically challenging condition that has a poor prognostic implication. It is a result of plaque rupture with release of cholesterol crystals into the circulation that embolize into various tissue organs. Plaque rupture seems to be triggered by an expanding necrotic core during cholesterol crystallization forming sharp tipped crystals that perforate and tear the fibrous cap. Embolizing cholesterol crystals then initiate both local and systemic inflammation that eventually lead to vascular fibrosis and obstruction causing symptoms that can mimic other vasculitic conditions. In fact, animal studies have demonstrated that cholesterol crystals can trigger an inflammatory response via NLRP3 inflammasome similar to that seen with gout. The diagnosis of CCE syndrome often requires a high suspicion of the condition. Serum inflammation biomarkers including elevated sedimentation rate, abnormal renal function tests and eosinophilia are useful but non-specific. Common target organ involvement includes the skin, kidney, and brain. Various testing including fundoscopic eye examination and other non-invasive procedures such as trans-esophageal echocardiography and magnetic resonance imaging may be helpful in identifying the embolic source. Treatment includes aspirin and clopidogrel, high dose statin and possibly steroids. In rare cases, mechanical intervention using covered stents may help isolate the ruptured plaque. Anticoagulation with warfarin is not recommended and might even be harmful. Overall, CCE syndrome is usually a harbinger of extensive and unstable atherosclerotic disease that is often associated with acute cardiovascular events.

All that looks like “Brugada” is not “Brugada”: Case series of Brugada phenocopy caused by hyponatremia

Brugada syndrome (BS), a life-threatening channelopathy associated with reduced inward sodium current due to dysfunctional sodium channels, is characterized by ST-segment elevation with downsloping “coved type” (type 1) or “saddle back” (type 2) pattern in V1–V3 precordial chest leads (1, 2). Brugada phenocopy, a term describing conditions inducing Brugada-like pattern of electrocardiogram (EKG) manifestations in patients without true BS, is an emerging condition (3). We describe a case series of Brugada phenocopy with hyponatremia.

A star in the eye: cat scratch neuroretinitis

Neuroretinitis is one of the atypical presentations of Cat scratch disease (CSD). Fundoscopy showed star pattern macular exudates. CSD should be considered in patients who present with blurry vision and typical fundoscopic findings.

Isolated Left Main Coronary Artery Stenosis after Thoracic Radiation Therapy: To Operate or Not to Operate

Radiation therapy of neoplasms involving the chest or mediastinum results in a wide spectrum of cardiac complications including coronary artery disease, which can present in patients with few or no traditional cardiac risk factors. We report a case of radiation induced coronary artery disease in a 60-year-old female with a history of stage IIIA nonsmall cell lung carcinoma which was diagnosed eight years earlier and treated with chemotherapy and radiotherapy. She presented to the hospital with atypical chest pain that had occurred intermittently over the preceding week. Her initial electrocardiogram and cardiac enzymes were within normal limits. However, following an indeterminate exercise nuclear stress test, she developed chest pain and elevated cardiac enzymes. Coronary angiography demonstrated 90% stenosis of the left main coronary artery ostium, without any evidence of atherosclerotic disease or stenosis in other coronary arteries. She underwent surgical revascularization, which revealed dense adhesions surrounding the heart. During surgery, she developed severe bleeding and died. Coronary artery disease can present within years of radiation exposure, and ostial lesions are typical. Treatment is often challenging because of the effects of radiation on other tissues and the risks of revascularization procedures. Therefore, a multidisciplinary team approach should be considered.