Fluoropyrimidines-5-fluorouracil (5-FU) and capecitabine-have been implicated as cardiotoxic chemotherapy agents. This rare, albeit potentially serious toxicity has been described in nearly four decades of case reports, case series, and in vitro modeling; however, there is a paucity in clinical trials and prospective analyses focused on cardioprotective strategies and cardiotoxic surveillance of these agents. While much attention has focused on the well-known cardiac toxicity of anthracyclines and monoclonal antibody agents such as trastuzumab, fluoropyrimidines remain one of the most common causes of chemotherapy-associated cardiotoxicity. The introduction of capecitabine, an oral prodrug of 5-FU, has made the treatment of solid tumors more convenient along with a subsequent rise in documented cardiotoxic cases. This review discusses the symptomatology, clinical manifestations, and proposed molecular mechanisms that attempt to describe the heterogeneous spectrum of fluoropyrimidine-induced cardiotoxicity. Four case examples showcasing the varied manifestations of cardiotoxicity are presented. Finally, several proposed management strategies for cardiotoxicity and post-hospital course precautions are discussed.

BACKGROUND-Microvascular dysfunction (MVD) is a potential cause of chest pain in younger individuals. We hypothesized that non-elderly patients referred for computed tomography coronary angiography (CTA) but without significant stenosis would have a high prevalence of MVD by myocardial contrast echocardiography (MCE). Secondary aims were to test whether the presence of non-obstructive CAD or reduced brachial flow-mediated dilation (FMD) predicted MVD. METHODS-Subjects ≤60 years-of-age undergoing CTA were recruited if they had either no evidence of coronary plaque, or evidence of mild CAD (<50% stenosis) and at least one high-risk plaque feature. Subjects underwent quantitative MCE perfusion imaging at rest and during regadenoson vasodilator stress. Microvascular dysfunction was defined by global or segmental delay of microvascular refill (≥2 seconds) during regadenoson. FMD of the brachial artery was also performed.

Boerhaave syndrome, a rare yet frequently fatal diagnosis, is characterized by the spontaneous transmural rupture of the esophagus. The classic presentation of Boerhaave syndrome is characterized by Mackler's triad, consisting of chest pain, vomiting, and subcutaneous emphysema. However, Boerhaave syndrome rarely presents with all the features of Mackler's triad; instead, the common presentation of Boerhaave syndrome includes chest or epigastric pain, severe retching and vomiting, dyspnea, and shock. These symptoms are typically misdiagnosed as cardiogenic in origin. Due to its atypical presentation, rarity, and mimicry of emergent conditions, diagnosis of Boerhaave syndrome is often delayed, resulting in a high mortality rate at the time of diagnosis and with a subsequent exponential increase in mortality if treatment is delayed by greater than 48 hours. Here, we report two atypical presentations of Boerhaave syndrome presenting as tension hydropneumothorax and review ten previously reported cases of Boerhaave syndrome presenting as tension hydropneumothorax. This review serves to raise clinician awareness about the expansive and elusive ways by which esophageal perforation may present, and thereby facilitate timely and potentially life-saving diagnosis.

Patent foramen ovale has been associated with multiple pulmonary diseases, such as pulmonary hypertension, platypnea-orthodeoxia syndrome, and chronic obstructive pulmonary disease. A connection between patent foramen ovale and chronic pulmonary disease was first described more than 2 decades ago in case reports associating patent foramen ovale with more severe hypoxemia than that expected based on the severity of the primary pulmonary disease. It has been suggested that patients with both chronic pulmonary disease and patent foramen ovale are subject to severe hypoxemia because of the right-to-left shunt. Furthermore, investigators have reported improved systemic oxygenation after patent foramen ovale closure in some patients with chronic pulmonary disease. This review focuses on the association between chronic pulmonary disease and patent foramen ovale and on the dynamics of a right-to-left shunt, and it considers the potential benefit of patent foramen ovale closure in patients who have hypoxemia that is excessive in relation to the degree of their pulmonary disease.

A 70-year old woman with history of longstanding rheumatoid arthritis and recent diagnosis of complete heart block leading to a dualchamber pacemaker im plantation presented to the hospital with several weeks of worsening dyspnoea and lower extremity swelling. On physical exam, she had evidence of both intraand extravascular fluid accumulation as evidenced by elevation in jugular venous pressure and lower extremity oedema. Electrocardiogram demonstrated normal pacemaker function with atrial-sensed, ventricular-paced rhythm. Echocardiography showed moderate-severe increased wall thickness with moderately reduced left ventricular ejection fraction (Supplementary material online, Videos S1-S4). Diastolic parameters were consistent with a Grade III abnormal filling pattern, low mitral annular tissue velocity, and a global longitudinal strain (GLS) of À9.4% with associated relative apical sparing (ratio of apical/basal segments 1.2). Given concern for an infiltrative cardiomyopathy, she underwent 99m technetium pyrophosphate scintigraphy revealing semiquantitative visual Grade 3 and diffuse uptake (Perugini Grade 3) on single-photon emission computed tomography. Serum immunofixation, free light chains, and alpha galactosidase A were normal. Right ventricular biopsy was negative on Congo red staining. Electron microscopy revealed disorganized myofibrils, abundant vacuoles, multiple lamellar inclusion bodies, and curvilinear cytoplasmic bodies, findings that are pathognomonic for hydroxychloroquine-induced restrictive cardiomyopathy (Figure). Hydroxychloroquine was discontinued, and the patient started on guideline directed heart failure therapy. Several months later, repeat echocardiography revealed modest improvement in left ventricular ejection fraction.Hydroxychloroquine accumulates in lysosomes, inhibiting molecular breakdown with resultant accumulation of phospholipids and glycogen. Clinical presentation includes biventricular hypertrophy, restrictive physiology (late-stage), and conduction system abnormalities. Importantly, in an era when bone scintigraphy is being used with increasing frequency to diagnose transthyretin (ATTR) amyloid cardiomyopathy, we hope to raise awareness for the potential of a false-positive result in patients taking hydroxychloroquine.Hydroxychloroquine-induced restrictive cardiomyopathy. (Panel A) Parasternal long-axis and apical views showing left ventricular concentric hypertrophy. (Panel B) Pulsed-wave and tissue Doppler showing a pseudo-normal filling pattern and depressed mitral annular velocity with a normal E/e 0 ratio. (Panel C) Polar map of the left ventricle showing relative apical sparing and a GLS of À9.4%. (Panel D) Diffuse uptake of 99m technetium pyrophosphate on planar imaging and single-photon emission computed tomography. (Panel E) Electron microscopy of a myocardial section obtained from an endomyocardial biopsy showing cytoplasmic changes of the cardiomyocyte including disorganization of myofibrils, lamellar inclusion bodies (red arrows), abundant vacuoles, and curvil...

Opinion statementThe increased risk for cardiovascular events in aging cancer survivors and those undergoing certain chemotherapeutic treatments has raised concern for more rigorous screening and surveillance methods above that of the general population. At this time, there are limited guidelines for how to best manage this vulnerable cohort. Questions regarding timing of screening, choice of imaging modality and risk reduction strategies-especially in those patients with known atherosclerotic disease-remain to be elucidated. Over a decade of case series, retrospective studies and clinical trials have shed light on the evolving role of cardiac computed tomography (CT) in this population, of which there is a relative paucity of data regarding its potential utility in the specific cardio-oncology population. Focusing on ability of cardiac CT to evaluate multiple cardiac and vascular structures, provide diagnostic and prognostic information, as well as assist interventional and surgical colleagues in surgical/percutaneous valve replacement and revascularization strategies is the premise for this review.

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Coronary microvascular dysfunction (MVD) is a syndrome of abnormal regulation of vascular tone, particularly during increased metabolic demand. While there are several risk factors for MVD, some of which are similar to those for coronary artery disease (CAD), the cause of MVD is not understood. We hypothesized that MVD in symptomatic non-elderly subjects would be characterized by specific lipidomic profiles. Subjects (n = 20) aged 35–60 years and referred for computed tomography coronary angiography (CTA) for chest pain but who lacked obstructive CAD (>50% stenosis), underwent quantitative regadenoson stress-rest myocardial contrast echocardiography (MCE) perfusion imaging for MVD assessment. The presence of MVD defined by kinetic analysis of MCE data was correlated with lipidomic profiles in plasma measured by liquid chromatography and high-resolution mass spectrometry. Nine of twenty subjects had evidence of MVD, defined by reduced hyperemic perfusion versus other subjects (beta-value 1.62 ± 0.44 vs. 2.63 ± 0.99 s−1, p = 0.009). Neither the presence of high-risk but non-obstructive CAD on CTA, nor CAD risk factors were different for those with versus without MVD. Lipidomic analysis revealed that patients with MVD had lower concentrations of long-carbon chain triacylglycerols and diacylglycerols, and higher concentrations of short-chain triacylglycerols. The diacylglycerol containing stearic and linoleic acid classified all participants correctly. We conclude that specific lipidomic plasma profiles occur in MVD involving saturated long-chain fatty acid-containing acylglycerols that are distinctly different from those in non-obstructive CAD. These patterns could be used to better characterize the pathobiology and potential treatments for this condition.