Cardio-Oncology Training: A Proposal From the International Cardioncology Society and Canadian Cardiac Oncology Network for a New Multidisciplinary Specialty.

There is an increasing awareness and clinical interest in cardiac safety during cancer therapy as well as in optimally addressing cardiac issues in cancer survivors. Although there is an emerging expertise in this area, known as cardio-oncology, there is a lack of organization in the essential components of contemporary training. This proposal, an international consensus statement organized by the International Cardioncology Society and the Canadian Cardiac Oncology Network, attempts to marshal the important ongoing efforts for training the next generation of cardio-oncologists. The necessary elements are outlined, including the expectations for exposure necessary to develop adequate training. There should also be a commitment to local, regional, and international education and research in cardio-oncology as a requirement for advancement in the field.

Prediction of response to cardiac resynchronization therapy using left ventricular pacing lead position and cardiovascular magnetic resonance derived wall motion patterns: a prospective cohort study.

BACKGROUND: Despite marked benefits in many heart failure patients, a considerable proportion of patients treated with cardiac resynchronization therapy (CRT) fail to respond appropriately. Recently, a "U-shaped" (type II) wall motion pattern identified by cardiovascular magnetic resonance (CMR) has been associated with improved CRT response compared to a homogenous (type I) wall motion pattern. There is also evidence that a left ventricular (LV) lead localized to the latest contracting LV site predicts superior response, compared to an LV lead localized remotely from the latest contracting LV site. METHODS: We prospectively evaluated patients undergoing CRT with pre-procedural CMR to determine the presence of type I and type II wall motion patterns and pre-procedural echocardiography to determine end systolic volume (ESV). We assessed the final LV lead position on post-procedural fluoroscopic images to determine whether the lead was positioned concordant to or remote from the latest contracting LV site. CRT response was defined as a ≥ 15% reduction in ESV on a 6 month follow-up echocardiogram. RESULTS: The study included 33 patients meeting conventional indications for CRT with a mean New York Heart Association class of 2.8 ± 0.4 and mean LV ejection fraction of 28 ± 9%. Overall, 55% of patients were echocardiographic responders by ESV criteria. Patients with both a type II pattern and an LV lead concordant to the latest contracting site (T2CL) had a response rate of 92%, compared to a response rate of 33% for those without T2CL (p = 0.003). T2CL was the only independent predictor of response on multivariate analysis (odds ratio 18, 95% confidence interval 1.6-206; p = 0.018). T2CL resulted in significant incremental improvement in prediction of echocardiographic response (increase in the area under the receiver operator curve from 0.69 to 0.84; p = 0.038). CONCLUSIONS: The presence of a type II wall motion pattern on CMR and a concordant LV lead predicts superior CRT response. Improving patient selection by evaluating wall motion pattern and targeting LV lead placement may ultimately improve the response rate to CRT.

Bad company: supracristal VSD presenting with ruptured sinus of valsalva aneurysm. a case presentation with echocardiographic depiction and an analysis of contemporary literature.

Supracristal ventricular septal defect (SCVSD), a defect of the infundibular portion of the interventricular septum just below the right aortic cusp, occurs more frequently in Eastern Asian populations. SCVSD may be complicated by right sinus of Valsalva aneurysm (SoVA). We present the case of a 26-year-old male of Korean descent with a history of a childhood murmur who was referred to our institution for progressive heart failure symptoms. He was diagnosed with SCVSD and ruptured right SoVA based on history, physical exam, and echocardiography including three-dimensional transesophageal echocardiography with reconstructed surgical views. The patient underwent SCVSD closure, SoVA excision, and valve-sparing aortic root replacement. We reviewed the echocardiography literature regarding SCVSD and SoVA, and analyzed contemporary literature of SoVA and its relationship with SCVSD. We conclude that a higher prevalence of ruptured SoVA in Eastern Asians is likely related to a higher prevalence of underlying SCVSD in this population.

Relationship between mechanical dyssynchrony and intra-operative electrical delay times in patients undergoing cardiac resynchronization therapy.

BACKGROUND: It is important to understand the relationship between electrical and mechanical ventricular activation in CRT patients. By measuring local electrical activation at multiple locations within the coronary veins and myocardial contraction at the same locations in the left ventricle, we determined the relationship between electrical and mechanical activation at potential left ventricular pacing locations. METHODS: In this study, mechanical contraction times were computed using high temporal resolution cine cardiovascular magnetic resonance (CMR) data, while electrical activation times were derived from intra-procedural local electrograms. RESULTS: In our cohort, there was a strong correlation between electrical and mechanical delay times within each patient (R2=0.78 ± 0.23). Additionally, the latest electrically activated location corresponded with the latest mechanically contracting location in 91% of patients. CONCLUSIONS: This study provides initial evidence that our method of obtaining non-invasive mechanical activation patterns accurately reflects the underlying electromechanical substrate of intraventricular dyssynchrony.

The role of cardiovascular magnetic resonance in stratifying paravalvular leak severity after transcatheter aortic valve replacement: an observational outcome study.

BACKGROUND: Significant paravalvular leak (PVL) after transcatheter aortic valve replacement (TAVR) confers a worse prognosis. Symptoms related to significant PVL may be difficult to differentiate from those related to other causes of heart failure. Cardiovascular magnetic resonance (CMR) directly quantifies valvular regurgitation, but has not been extensively studied in symptomatic post-TAVR patients. METHODS: CMR was compared to qualitative (QE) and semi-quantitative echocardiography (SQE) for classifying PVL and prognostic value at one year post-imaging in 23 symptomatic post-TAVR patients. The primary outcome was a composite of all-cause death, heart failure hospitalization, and intractable symptoms necessitating repeat invasive therapy; the secondary outcome was a composite of all-cause death and heart failure hospitalization. The difference in event-free survival according to greater than mild PVL versus mild or less PVL by QE, SQE, and CMR were evaluated by Kaplan-Meier survival analysis. RESULTS: Compared to QE, CMR reclassified PVL severity in 48% of patients, with most patients (31%) reclassified to at least one grade higher. Compared to SQE, CMR reclassified PVL severity in 57% of patients, all being reclassified to at least one grade lower; SQE overestimated PVL severity (mean grade 2.5 versus 1.7, p=0.001). The primary and secondary outcomes occurred in 48% and 35% of patients, respectively. Greater than mild PVL by CMR was associated with reduced event-free survival for the primary outcome (p<0.0001), however greater than mild PVL by QE and SQE were not (p=0.83 and p=0.068). Greater than mild PVL by CMR was associated with reduced event-free survival for the secondary outcome, as well (p=0.012). CONCLUSION: In symptomatic post-TAVR patients, CMR commonly reclassifies PVL grade compared with QE and SQE. CMR provides superior prognostic value compared to QE and SQE, as patients with greater than mild PVL by CMR (RF>20%) had a higher incidence of adverse events.

Epicardial adipose tissue volume and coronary artery calcium to predict myocardial ischemia on positron emission tomography-computed tomography studies.

BACKGROUND: There appears to be an association of epicardial adipose tissue (EAT) with coronary artery disease (CAD) and its risk factors. EAT is assumed to influence CAD development by altering vasomotor tone and via toxic paracrine effects. The relationship of EAT to myocardial perfusion has not been studied. METHODS: Quantification of EAT and CAC was performed on positron emission tomography/computed tomography (PET/CT) studies in 45 subjects (77% intermediate pre-test probability of CAD) with mild-moderate myocardial ischemia (5-14% perfusion defect, n = 23), severe ischemia (≥15% defect, n = 22) and a control group with no ischemia matched for CAD risk factors (n = 52). RESULTS: EAT volume showed a better correlation with myocardial ischemia than total CAC (r = .47 vs r = .28, P < .01). EAT volume increased significantly from the control group to subjects with mild-moderate and severe ischemia (96.9, 124.5, and 143.9 cm(3), P < .01 for both ischemia groups vs controls). Total mean CAC was significantly higher in the severe ischemia group (676.3) than in control group (229.4) (P < .01). Multivariable logistic regression analyses showed that EAT volume was, but CAC was not, a significant predictor of ischemia after adjustment for age, sex, body mass index, and each other. EAT volume was a better predictor of ischemia than total CAC [area under the curve (AUC): .764 vs .6291, P = .04]. The combination of EAT + CAC (AUC = .7694) did not improve over EAT volume alone (P = .57). CONCLUSIONS: In this study, EAT volume assessed by CT was an independent predictor of ischemia on PET, and outperformed CAC score in a CAD naïve population at intermediate pre-test probability of disease.

Trastuzumab-induced cardiomyopathy: not as benign as it looks? A retrospective study.

BACKGROUND: One of the recent advances in the treatment of breast cancer is trastuzumab. However, a major side effect of this medication is cardiomyopathy. Our objective was to determine the incidence of trastuzumab-induced cardiomyopathy and the rate of discontinuation of trastuzumab in a clinical setting. METHODS AND RESULTS: We retrospectively reviewed the records of all women treated with trastuzumab at the Moffitt Cancer Center between 2003 and 2007. Cardiomyopathy was defined as symptomatic heart failure or a decrease of ejection fraction by >or=10% from baseline or to <50%. Statistical analysis was done with Fisher exact test, t-test test, and Wilcoxon signed rank test. Cardiomyopathy developed in 52 of 156 (33.3%) of patients being treated with trastuzumab. In the adjuvant group, 23 (19.5%) of women permanently or temporarily discontinued therapy secondary to cardiomyopathy. CONCLUSIONS: Cardiomyopathy is a common side effect of trastuzumab that leads to discontinuation of treatment in a significant proportion of patients. Further studies are indicated to establish the ways to predict, prevent, and treat cardiomyopathy to provide patients with maximal therapeutic benefit of trastuzumab.

When Hindsight Is 20/20: Stiff Left Atrium Syndrome Masquerading as Mitral Regurgitation.

Scarring from atrial ablation carries a risk of developing stiff left atrium syndrome, which can mimic mitral valve disease. We present a case of a 73-year-old man whose stiff left atrium syndrome came to light after percutaneous mitral valve repair. (Level of Difficulty: Intermediate.).

Internal Jugular Venous Pseudoaneurysm in a Patient with Heart Failure and Severe Tricuspid Regurgitation.

The differential diagnosis of a lateral neck mass includes a number of possible etiologies. While jugular venous aneurysms and pseudoaneurysms are rare entities, they should be considered in the differential diagnosis of a pulsatile lateral neck mass. We present a case of an idiopathic jugular venous pseudoaneurysm and its association with worsening tricuspid regurgitation in a patient with heart failure with preserved ejection fraction.

Developing a Comprehensive Cardio-Oncology Program at a Cancer Institute: The Moffitt Cancer Center Experience.

Cardio-oncology is a multidisciplinary field focusing on the management and prevention of cardiovascular complications in cancer patients and survivors. While the initial focus of this specialty was on heart failure associated with anthracycline use, novel anticancer agents are increasingly utilized and are associated with many other cardiotoxicities including hypertension, arrhythmias and vascular disease. Since its inception, the field has developed at a rapid pace with the establishment of programs at many major academic institutions and community practices. Given the complexities of this patient population, it is important for providers to possess knowledge of not only cardiovascular disease but also cancer subtypes and their specific therapeutics. Developing a cardio-oncology program at a stand-alone cancer center can present unique opportunities and challenges when compared to those affiliated with other institutions including resource allocation, cardiovascular testing availability and provider education. In this review, we present our experiences establishing the cardio-oncology program at Moffitt Cancer Center and provide guidance to those individuals interested in developing a program at a similar independent cancer institution.

Diagnosis Using CCTA and Management of Anomalous Right Coronary Artery from the Opposite Sinus.

Coronary anomalies can be observed in 1-1.2% of all angiograms performed. Majority of coronary anomalies are benign and do not lead to cardiac ischemia; however anomalous coronary arteries from the opposite sinus (ACAOS) are often associated with sudden cardiac deaths, typically in 0.11-0.35% of individuals who participate in vigorous physical activity (Peñalver et al., 2012). Left and right ACAOS have an incidence of 0.15% and 0.92%, respectively. Left ACAOS are often associated with higher incidence of sudden cardiac death; this could be secondary to greater territory of myocardial perfusion by the left coronary artery. ACAOS are often asymptomatic and initially present as sudden death following exertion in young athletes. The management of left ACAOS is clear and surgery is usually indicated. However there is a lack of consensus on the management of certain cases of right ACAOS. In this paper a case of 20 yo M with right coronary artery from left sinus is going to be presented with a discussion on pathophysiology, diagnosis, and management.

Transapical closure of a pseudoaneurysm of the mitral-aortic intervalvular fibrosa.

Pseudoaneurysm of the mitral-aortic intervalvular fibrosa is a rare but serious sequela of endocarditis or valve replacement surgery. Because open-heart surgery is a high-risk treatment option, alternative methods are sought. We present the case of a 77-year-old man with a noninfected mechanical mitral valve whose pseudoaneurysm was repaired by introducing an occluder device into the defect by a transapical approach. Upon follow-up imaging, the defect was successfully closed. We conclude that percutaneous closure of pseudoaneurysm of the mitral-aortic intervalvular fibrosa is a viable alternative to surgery and that a transapical approach is an appropriate method of access.

The prognostic value of standardized reference values for speckle-tracking global longitudinal strain in hypertrophic cardiomyopathy.

Speckle-tracking left ventricular global longitudinal strain (GLS) assessment may provide substantial prognostic information for hypertrophic cardiomyopathy (HCM) patients. Reference values for GLS have been recently published. We aimed to evaluate the prognostic value of standardized reference values for GLS in HCM patients. An analysis of HCM clinic patients who underwent GLS was performed. GLS was defined as normal (more negative or equal to -16%) and abnormal (less negative than -16%) based on recently published reference values. Patients were followed for a composite of events including heart failure hospitalization, sustained ventricular arrhythmia, and all-cause death. The power of GLS to predict outcomes was assessed relative to traditional clinical and echocardiographic variables present in HCM. 79 HCM patients were followed for a median of 22 months (interquartile range 9-30 months) after imaging. During follow-up, 15 patients (19%) met the primary outcome. Abnormal GLS was the only echocardiographic variable independently predictive of the primary outcome [multivariate Hazard ratio 5.05 (95% confidence interval 1.09-23.4, p = 0.038)]. When combined with traditional clinical variables, abnormal GLS remained independently predictive of the primary outcome [multivariate Hazard ratio 5.31 (95 % confidence interval 1.18-24, p = 0.030)]. In a model including the strongest clinical and echocardiographic predictors of the primary outcome, abnormal GLS demonstrated significant incremental benefit for risk stratification [net reclassification improvement 0.75 (95 % confidence interval 0.21-1.23, p < 0.0001)]. Abnormal GLS is an independent predictor of adverse outcomes in HCM patients. Standardized use of GLS may provide significant incremental value over traditional variables for risk stratification.

Multimodality imaging of aortitis.

Multimodality imaging of aortitis is useful for identification of acute and chronic mural changes due to inflammation, edema, and fibrosis, as well as characterization of structural luminal changes including aneurysm and stenosis or occlusion. Identification of related complications such as dissection, hematoma, ulceration, rupture, and thrombosis is also important. Imaging is often vital for obtaining specific diagnoses (i.e., Takayasu arteritis) or is used adjunctively in atypical cases (i.e., giant cell arteritis). The extent of disease is established at baseline, with associated therapeutic and prognostic implications. Imaging of aortitis may be useful for screening, routine follow up, and evaluation of treatment response in certain clinical settings. Localization of disease activity and structural abnormality is useful for guiding biopsy or surgical revascularization or repair. In this review, we discuss the available imaging modalities for diagnosis and management of the spectrum of aortitis disorders that cardiovascular physicians should be familiar with for facilitating optimal patient care.

Effect of intensive versus moderate lipid-lowering therapy on epicardial adipose tissue in hyperlipidemic post-menopausal women: a substudy of the BELLES trial (Beyond Endorsed Lipid Lowering with EBT Scanning).

OBJECTIVES: This study sought to evaluate the effect of intensive and moderate statin therapy on epicardial adipose tissue (EAT). BACKGROUND: EAT has been associated with coronary artery disease severity and outcome. It is currently unknown whether EAT volume changes over time when patients are exposed to statin therapy. METHODS: Subanalysis of a randomized study of atorvastatin 80 mg/day versus pravastatin 40 mg/day for 1 year in a clinical trial designed to assess the progression of coronary artery calcium (CAC) in hyperlipidemic post-menopausal women. Patients underwent cardiac computed tomography scans at the start and end of the trial period. RESULTS: Of 420 patients, 194 received atorvastatin and 226 pravastatin; the median low-density lipoprotein change was -53.3% and -28.3% with atorvastatin and pravastatin, respectively (p < 0.001). Baseline EAT correlated with age, body mass index, hypertension, diabetes mellitus, high-density lipoprotein, triglyceride levels, and CAC (p < 0.001). At the end of follow-up, EAT regressed more in the atorvastatin than in the pravastatin group (median, -3.38% vs. -0.83%, p = 0.025). The EAT percent change from baseline was significant in the atorvastatin, but not the pravastatin group (p < 0.001 and p = 0.2, respectively). There was no correlation between lipid lowering and EAT regression. CAC progressed significantly in both groups from baseline. CONCLUSIONS: In hyperlipidemic post-menopausal women, statin therapy induced EAT regression, although intensive therapy was more effective than moderate-intensity therapy. This effect does not seem linked to low-density lipoprotein lowering and may be secondary to other actions of statins such as anti-inflammatory effects.

Association of epicardial adipose tissue with cardiometabolic risk and metabolic syndrome in patients with rheumatoid arthritis.

OBJECTIVE: Patients with rheumatoid arthritis (RA) have increased coronary atherosclerosis possibly related to increased prevalence of visceral adiposity, insulin resistance, and metabolic syndrome. Epicardial adipose tissue (EAT), a type of visceral fat, may contribute to cardiometabolic risk. The aim of this study was to measure EAT volume in patients with RA and determine its relationship with cardiometabolic risk markers and coronary artery calcium. METHODS: EAT volume and coronary artery calcium score were measured by noncontrast cardiac computed tomography and compared in RA patients (n = 162) and controls (n = 89). The relationships between EAT volume and markers of cardiometabolic risk in RA were examined with adjustment for age, race, and sex. RESULTS: Among RA patients, EAT volume was positively associated with interleukin-6 (P = 0.03), triglycerides (P = 0.004), hypertension (P = 0.01), homeostatic model of insulin resistance (HOMA) (P < 0.001), smoking history (P = 0.04), and homocysteine level (P = 0.001), and negatively associated with high-density lipoprotein (P = 0.005). With further adjustment for waist circumference (a measure of visceral obesity), EAT volume remained independently associated with triglycerides, HOMA, current smoking, and homocysteine level (all P < 0.05). EAT volume was not associated with corticosteroid use or coronary artery calcium score. Patients with metabolic syndrome had significantly greater EAT volume (P < 0.001) and each increase in metabolic syndrome criteria was associated, on average, with a 20% increase (95% confidence interval 14-26%) in EAT volume (P < 0.001). CONCLUSION: EAT volume is associated with metabolic syndrome and cardiometabolic risk factors, including insulin resistance, triglycerides, current smoking, and homocysteine levels, but not with coronary artery calcium in RA patients.

Prognostic value of adenosine stress cardiovascular magnetic resonance and dobutamine stress echocardiography in patients with low-risk chest pain.

Excluding obstructive coronary artery disease (CAD) as the etiology of acute chest pain in patients without diagnostic electrocardiographic changes or elevated serum cardiac biomarkers is challenging. Stress testing is a valuable risk-stratifying technique reserved for the subset of these patients with low-risk chest pain who have an intermediate clinical probability of obstructive CAD. Given the risks of radiation inherent to nuclear and computed tomography imaging, both adenosine stress cardiovascular magnetic resonance (AS-CMR) imaging and dobutamine stress echocardiography (DSE) are attractive alternative stress modalities. An essential characteristic of stress modalities is their negative prognostic value; as one must exclude clinically-relevant CAD such that patients can be discharged safely. Therefore, the aim of this study was to validate a favorable negative prognostic value for both AS-CMR and DSE in patients presenting with low-risk acute chest pain. This retrospective study included 255 patients with low-risk acute chest pain and no prior history of CAD presenting to the emergency department at our institution, with 89 patients evaluated by AS-CMR and 166 by DSE. Median follow-up was 292 days, and consisted of medical record review. The primary end-point was the composite of cardiac death, nonfatal acute myocardial infarction, obstructive CAD on invasive coronary angiography (ICA) or recurrent chest pain requiring hospital admission. Test characteristics such as sensitivity and specificity could not be evaluated as patients were not routinely evaluated with ICA. All patients completed the stress protocol without adverse events during testing. 82/89 patients (92.1%) and 164/166 patients (98.8%) had negative AS-CMR and DSE studies, respectively. Both AS-CMR and DSE had excellent negative prognostic values for the primary endpoint, 100 and 99%, respectively. Both AS-CMR and DSE are effective stress modalities for excluding clinically significant coronary artery disease in patients presenting acute low-risk chest pain. Patients without findings to suggest ischemia have an excellent intermediate-term prognosis.

Epicardial adipose tissue is increased in patients with systemic lupus erythematosus.

OBJECTIVE: Morbidity and mortality secondary to premature cardiovascular disease (CVD) in systemic lupus erythematosus (SLE) remain significant issues. The pathogenesis of CVD in SLE patients has not been fully explored. Epicardial adipose tissue (EAT) is believed to contribute to atherosclerosis development, through a paracrine and systemic inflammatory effect. We measured EAT volume in 162 SLE patients and 86 matched controls to assess the association of EAT with markers of atherosclerosis, cardiovascular risk and immunoactivation. METHODS: Clinical and laboratory characteristics collected included anthropomorphic measures, disease activity and damage indices, blood pressure measurement, lipid profile, inflammatory indices, adipokine levels and measures of adiposity. Coronary artery calcium (CAC) and EAT volume were measured using non-contrast cardiac computed tomography. RESULTS: EAT volume was greater in patients with SLE [(mean ± SD) 96.8 ± 45.9 cm(3)] than controls (78.2 ± 40.7 cm(3); P = 0.001). The EAT volume was 31% larger (95% CI, 16.5%-47.4%) in SLE patients than controls (P < 0.001 adjusted for age, sex, and race; after additional adjustment for waist circumference P = 0.007). Within SLE patients, after adjusting for age, race, sex, and waist circumference, EAT volume was associated with cumulative corticosteroid dose (P = 0.007), current corticosteroid use (P < 0.001), HDL cholesterol (P = 0.033), and triglycerides (P = 0.005). EAT was significantly correlated with CAC score (P < 0.001), but the association was attenuated after adjustment for Framingham risk score (P = 0.051). CONCLUSION: The increased EAT volume seen in SLE patients is associated with corticosteroid use. Corticosteroids could have adverse cardiovascular effects in SLE via an increase in EAT volume, a marker of risk in the general population.

Takotsubo cardiomyopathy presenting with dyspnea.

Takotsubo cardiomyopathy (TC), or "broken heart syndrome", is an increasingly recognized condition that mimics acute myocardial infarction with morphologically characteristic left ventricular dysfunction in the absence of coronary artery disease. TC is seen almost exclusively in postmenopausal women following extreme emotional or physiologic stress. Although most patients present with chest pain, limited data suggest that African American patients with TC tend to present with atypical symptoms such as dyspnea or nausea. We present a 57 year-old African American female with TC who presented with severe dyspnea following the shooting death of her son. Added to existing data, our case alerts clinicians to consider Takotsubo syndrome in African American patients with atypical presentation.