Trastuzumab and pertuzumab in hemodialysis: A case report.

INTRODUCTION: Trastuzumab and pertuzumab are recombinant humanized monoclonal antibodies targeting human epidermal growth factor receptor 2 (HER2). Currently, six reported cases on the use of trastuzumab in dialysis, and one on the use of pertuzumab, have been identified in the literature. This case is one of the first to describe the use of pertuzumab, and adds to currently available reports on the use of trastuzumab, in hemodialysis. CASE REPORT: A female receiving hemodialysis three times per week was diagnosed with a clinical T2N1M0, hormone receptor-negative, HER2-positive, invasive ductal carcinoma of the breast. She received six cycles of neoadjuvant docetaxel, carboplatin, trastuzumab, and pertuzumab, with left ventricular ejection fraction (LVEF) remaining stable throughout. Following surgery, she continued dual HER2 blockade with trastuzumab and pertuzumab, after six cycles of which she was found on routine echocardiogram to have an asymptomatic decline in LVEF.Management & outcome: Following the decline in LVEF, trastuzumab and pertuzumab were held, and cardio-oncology was consulted. LVEF recovered within one month, after which she continued on single-agent trastuzumab to complete one year of HER2-directed therapy. DISCUSSION: To our knowledge, this is one of the first published cases describing the use of pertuzumab in a patient receiving hemodialysis. Though our patient did experience a reversible decline in LVEF following twelve cycles of combination trastuzumab and pertuzumab, this case demonstrates the relatively safe and effective use of pertuzumab in a patient with end-stage renal disease undergoing hemodialysis, and lends additional support to the use of trastuzumab in this particular patient population.

The role and clinical effectiveness of multimodality imaging in the management of cardiac complications of cancer and cancer therapy.

With the increasing number of individuals living with a current or prior diagnosis of cancer, it is important for the cardiovascular specialist to recognize the various complications of cancer and its therapy on the cardiovascular system. This is true not only for established cancer therapies, such as anthracyclines, that have well established cardiovascular toxicities, but also for the new targeted therapies that can have "off target" effects in the heart and vessels. The purpose of this informational statement is to provide cardiologists, cardiac imaging specialists, cardio-oncologists, and oncologists an understanding of how multimodality imaging may be used in the diagnosis and management of the cardiovascular complications of cancer therapy. In addition, this document is meant to provide useful general information concerning the cardiovascular complications of cancer and cancer therapy as well as established recommendations for the monitoring of specific cardiotoxic therapies.

Echocardiographic Differences in Women Across Subtypes of Hypertensive Disorders of Pregnancy.

Background: Hypertensive disorders of pregnancy (HDP) can be classified into gestational hypertension, preeclampsia (PRE), and chronic hypertension with superimposed preeclampsia (SPE). Objectives: The purpose of this study was to retrospectively examine the echocardiographic differences in biventricular structure and function in 3 HDP groups of women in comparison to normotensive pregnant controls. Methods: Women with an echocardiogram during or within the first year of pregnancy were identified within our integrated health network. Exclusion criteria included age <18 years, diagnosis of pulmonary embolism, malignancy, autoimmune disease, and structural heart disease. Results: We identified a total of 706 subjects (cases: n = 427, normotensive controls: n = 279). Cases were divided into 3 groups: gestational hypertension (n = 57), PRE (n = 291), and SPE (n = 79). In adjusted analyses, echocardiographic parameters demonstrated a graded difference in left ventricular (LV) mass index, relative wall thickness, mitral inflow E, mitral inflow A, septal e', lateral e', E/e', left atrial volume index, tricuspid velocity, and lateral e' velocities with the most profound findings noted in the SPE group. Specifically, adjusted LV mass index (adjusted ß = 14.45, 95% CI: 9.00-19.90) and E/e' (adjusted ß = 2.97, 95% CI: 2.27-3.68) was highest in the SPE group in comparison to controls (P < 0.001). Conclusions: LV remodeling and diastolic filling abnormalities are more common in HDP and are most evident in SPE and PRE. Echocardiography during or immediately after pregnancy may be useful in these high-risk women to identify these abnormalities. The long-term implications of these echocardiographic abnormalities require further study.

Hyperlipidemia and risk for preclampsia.

Hypertensive disorders of pregnancy are among the leading causes of maternal morbidity and mortality in the US. Preeclampsia (PreE) which includes hypertension and proteinuria during pregnancy, is thought to result from placental ischemia. Risk factors for PreE parallel those for cardiovascular disease, and recent studies point to hyperlipidemia specifically, hypertriglyceridemia, as a risk factor for PreE. Current practice does not routinely include lipid testing pre-conception or during pregnancy. Professional, societal recommendations should advocate for hyperlipidemia screening, followed by appropriate management, pre-conception and during pregnancy.

Ethnic and Racial Disparities in Resource Utilization and In-hospital Outcomes Among Those Admitted for Atrial Fibrillation: A National Analysis.

Disparities in overall outcomes for atrial fibrillation (AF) across racial and ethnic groups have been demonstrated in prior studies. We aim to evaluate in-hospital outcomes and resource utilization across 3 racial/ethnic groups with AF using contemporary data. We identified patients admitted with AF in the National Inpatient Sample registry from 2015 to 2018. ICD-10-CM codes were used to identify variables of interest. The primary outcomes were in-hospital complications and resource utilization. There were 1,250,075 AF admissions. Our sample was made up of 85.49% White, 8.12% Black, and 6.38% Hispanic patients. Black patients were younger but had a higher burden of cardiovascular comorbidities including obesity, hypertension, and chronic kidney disease. Social determinants were also less favorable in Black patients, with a higher percentage of Medicaid insurance and a high proportion of patients being in the lowest percentile for household income. Total hospital charge was highest in Hispanic patients. Despite higher rates of gastrointestinal bleed, Black patients were least likely to undergo left atrial appendage occlusion device implantation. Black and Hispanic patients were less like to undergo catheter ablation therapy. Black race was an independent predictor of mortality, stroke, mechanical ventilation, acute kidney injury, hemodynamic shock, need for vasopressor, upper gastrointestinal bleed, need for blood transfusion, total hospital charges, and length of stay when compared to other groups. Disparities exist in the risk of AF, and its management among racial and ethnic groups. Health care costs and inpatient outcomes disproportionately impact minorities in the United States.

Cardiac Sarcoidosis Causing Ventricular Tachycardia After Myocardial Infarction: A Shocking Diagnosis.

Scar-mediated ventricular tachycardia (VT) commonly results from ischemic heart disease. We present a case of recurrent VT, which was initially attributed to ischemic disease; however, the scar location pointed to an alternate pathology. This case demonstrates the utility of multimodality imaging in diagnosing sarcoidosis as a cause of VT. (Level of Difficulty: Intermediate.).

Sex-Based Differences in Left Ventricular Assist Device Utilization: Insights From the Nationwide Inpatient Sample 2004 to 2016.

BACKGROUND: Women comprise approximately one-third of the advanced heart failure population but may receive fewer advanced heart failure therapies including left ventricular assist devices (LVADs). During the early pulsatile-flow device era, women had higher post-LVAD mortality and increased complications. However, knowledge about these differences in the continuous-flow device era is limited. Therefore, we sought to explore temporal trends in LVAD utilization and post-LVAD mortality by sex. METHODS AND RESULTS: Patients with LVAD implantation from 2004 to 2016 were identified using the Nationwide Inpatient Sample. Trends in LVAD utilization and post-LVAD inpatient mortality were compared by sex and device era. Although LVADs are being increasingly utilized for patients with advanced systolic heart failure, women continue to represent a smaller proportion of LVAD recipients-25.8% in 2004 to 21.9% in 2016 (P for trend, 0.91). Women had increased inpatient mortality after LVAD implantation compared with men in the pulsatile-flow era (46.9% versus 31.1%, P<0.0001) but not in the continuous-flow era (13.3% versus 12.1%, P=0.27; P for interaction=0.0002). Inpatient mortality decreased for both sexes over time after LVAD, with a sharp fall in 2008 to 2009. Female sex was independently associated with increased post-LVAD inpatient mortality beyond adjustment for demographics and risk factors during the pulsatile-flow era (odds ratio, 2.13; 95% CI, 1.45-3.10; P<0.0001) but not during the continuous-flow era (1.18; 0.93-1.48; P=0.16). CONCLUSIONS: Although utilization of LVAD therapy increased over time for both sexes, LVAD implantation remains stably lower in women, which may suggest a potential underutilization of this potentially life-saving therapy. Prospective studies are needed to confirm these findings.

Diabetic cardiomyopathy: the search for a unifying hypothesis.

Although diabetes is recognized as a potent and prevalent risk factor for ischemic heart disease, less is known as to whether diabetes causes an altered cardiac phenotype independent of coronary atherosclerosis. Left ventricular systolic and diastolic dysfunction, left ventricular hypertrophy, and alterations in the coronary microcirculation have all been observed, although not consistently, in diabetic cardiomyopathy and are not fully explained by the cellular effects of hyperglycemia alone. The recent recognition that diabetes involves more than abnormal glucose homeostasis provides important new opportunities to examine and understand the impact of complex metabolic disturbances on cardiac structure and function.

Coronary Artery Calcification (CAC) and Post-Trial Cardiovascular Events and Mortality Within the Women's Health Initiative (WHI) Estrogen-Alone Trial.

BACKGROUND: Among women aged 50 to 59 years at baseline in the Women's Health Initiative (WHI) Estrogen-Alone (E-Alone) trial, randomization to conjugated equine estrogen-alone versus placebo was associated with lower risk of myocardial infarction and mortality, and, in an ancillary study, the WHI-CACS (WHI Coronary Artery Calcification Study) with lower CAC, measured by cardiac computed tomography ≈8.7 years after baseline randomization. We hypothesized that higher CAC would be related to post-trial coronary heart disease (CHD), cardiovascular disease (CVD), and total mortality, independent of baseline randomization or risk factors. METHODS AND RESULTS: WHI-CACS participants (n=1020) were followed ≈8 years from computed tomography scan in 2005 (mean age=64.4) through 2013 for incident CHD (myocardial infarction and fatal CHD, n=17), CVD (n=69), and total mortality (n=55). Incident CHD and CVD analyses excluded women with CVD before scan (n=89). Women with CAC=0 (n=54%) had very low age-adjusted rates/1000 person-years of CHD (0.91), CVD (5.56), and mortality (3.45). In comparison, rates were ≈2-fold higher for women with any CAC (>0). Associations were not modified by baseline randomization to conjugated equine estrogen-alone versus placebo. Adjusted for baseline randomization and risk factors, the hazard ratio (95% confidence interval) for CAC >100 (19%) was 4.06 (2.11, 7.80) for CVD and 2.70 (1.26, 5.79) for mortality. CONCLUSIONS: Among a subset of postmenopausal women aged 50 to 59 years at baseline in the WHI E-Alone Trial, CAC at mean age of 64 years was strongly related to incident CHD, CVD, and to total mortality over ≈8 years, independent of baseline randomization to conjugated equine estrogen-alone versus placebo or CVD risk factors. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov. Unique identifier: NCT00000611.

Triple threat in pregnancy.

A woman aged 22 years with a history of lupus presented in the 18th week of pregnancy with hypertensive emergency and flash pulmonary oedema. Bedside echocardiogram revealed severe left ventricular (LV) dysfunction with an ejection fraction (EF) of 25% and pericardial effusion. Laboratories revealed hypocomplementemia, proteinuria, elevated C reactive protein and anti-DS-DNA, raising concern for a lupus flare. Cardiac MRI showed an acute intramyocardial oedematous process, consistent with lupus carditis, and further worsening of LVEF to 13%. Shared-decision-making with the patient included discussion of maternal risks of continuation of pregnancy in the setting of worsening heart function and the fetal risks of definitive treatment with cyclophosphamide for a lupus flare and the patient decided to proceed with medical termination of pregnancy. Treatment with immunosuppressants, including cyclophosphamide, and steroids, was then initiated. 2 months after discharge, cardiac MRI showed marked improvement in LVEF to 50% and the patient remains clinically free of heart failure.

Utility of myocardial perfusion imaging in patients with low-risk treadmill scores.

OBJECTIVES: The purpose of this study was to determine whether a previously validated clinical score (CS) could identify patients with a low-risk Duke treadmill score who had a higher risk of adverse events and, therefore, in whom myocardial perfusion imaging would be valuable for risk stratification. BACKGROUND: Current American College of Cardiology/American Heart Association guidelines recommend using a standard exercise test without imaging as the initial test in patients who have an interpretable electrocardiogram and are able to exercise. METHOD: We studied 1,461 symptomatic patients with low-risk Duke treadmill scores (> or =5) who underwent myocardial perfusion imaging. The CS was derived by assigning one point to each of the following variables: typical angina, history of myocardial infarction, diabetes, insulin use, male gender, and each decade of age over 40 years. A CS cutoff > or =5 or <5 was used to categorize patients as high risk (n = 303 [21%]) or low risk (n = 1,158 [79%]). Perfusion scans were categorized as low, intermediate, or high risk on the basis of the global stress score (GSS). RESULTS: High-risk scans were more common in patients with a high-risk CS (26.4% vs. 9.5%, p < 0.0001). The CS and GSS were significant independent predictors of cardiac death. However, in patients with a low CS, seven-year cardiac survival was excellent, regardless of the GSS (99% for normal scans, 99% for mildly abnormal scans, and 99% for severely abnormal scans). In contrast, patients with a high CS had a lower seven-year survival rate (92%), which varied with GSS (94% for normal scans, 94% for mildly abnormal scans, and 84% for severely abnormal scans; p < 0.001). CONCLUSIONS: In symptomatic patients with low-risk Duke treadmill scores and low clinical risk, myocardial perfusion imaging is of limited prognostic value. In patients with low-risk Duke treadmill scores and high clinical risk, annual cardiac mortality (>1%) is not low, and myocardial perfusion imaging has independent prognostic value.

Prognostic value of exercise stress myocardial perfusion imaging in patients with permanent pacemakers.

One hundred eight patients with single- or dual-chamber pacemakers underwent exercise myocardial perfusion imaging with thallium-201 or technetium-99m sestamibi. A high-risk scan (a large fixed defect, a large reversible defect, or evidence of cardiomyopathy) identified patients at high risk for cardiac death on both a univariate and multivariate basis.

Acute myocardial infarction associated with dietary supplements containing 1,3-dimethylamylamine and Citrus aurantium.

We describe the case of a previously healthy 22-year-old man who presented with anginal chest pain and was diagnosed with a non-ST-elevation myocardial infarction. For 3 weeks, he had been ingesting the dietary supplements Jack3d® (principal ingredient, 1,3-dimethylamylamine) and Phenorex™ (principal ingredient, Citrus aurantium) daily, before undertaking physical activity. Coronary angiograms revealed a proximal left anterior descending coronary artery thrombus with distal embolization. A combined medical regimen led to resolution of the thrombus. Three months later, the patient was asymptomatic with no evidence of ischemia. The primary ingredients in the sympathomimetic supplements taken by our patient are controversial in the medical community and have been individually associated with adverse cardiac events. There are no safety data on their simultaneous use. We discuss other reports of adverse effects associated with these supplements and recommend that the relevant safety guidelines be revised.

Relationship between circulating serum osteoprotegerin and total receptor activator of nuclear κ-B ligand levels, triglycerides, and coronary calcification in postmenopausal women.

OBJECTIVE: This study evaluates the relationship of blood osteoprotegerin (OPG) and receptor activator of nuclear κ-B ligand (RANKL) levels with coronary artery calcium (CAC) and cardiovascular risk factors in two studies of postmenopausal women. OPG, a marker of bone turnover, and its ligand, RANKL, may contribute to cardiovascular disease risk. METHODS: We tested the hypothesis that serum OPG and RANKL levels were associated with CAC and cardiovascular disease risk factors among postmenopausal women in the Women On the Move through Activity and Nutrition Study (WOMAN Study; n = 86; mean [SD], age 58 [2.9] y) and replicated our findings in the Healthy Women Study (HWS; n = 205; mean [SD] age, 61 [2.3] y). Serum OPG, total RANKL, and CAC were measured at baseline and 48 months in the WOMAN Study and on the eighth postmenopausal visit in the HWS. RESULTS: In the WOMAN Study, higher OPG was associated with higher CAC, and higher total RANKL was associated with lower CAC and triglycerides. In the HWS, higher total RANKL was also associated with lower CAC and triglycerides. In logistic regression models adjusted for body mass index and triglycerides, the odds ratios (95% CIs) for CAC per unit increase in OPG were 1.78 (1.17-2.73) for the WOMAN Study and 1.02 (0.84-1.24) for the HWS, and the odds ratios (95% CIs) for CAC per unit increase in log total RANKL were 0.86 (0.64-1.17) for the WOMAN Study and 0.83 (0.72-0.96) for the HWS. CONCLUSIONS: The inverse association of total RANKL with CAC and triglycerides is a new finding and may have important implications given the increasing use of drugs that modify total RANKL and its receptor, receptor activator of nuclear κ-B.

The prognostic value of pharmacologic stress myocardial perfusion imaging in patients with permanent pacemakers.

BACKGROUND: The aim of this study is to assess the prognostic value of pharmacologic stress (adenosine or dipyridamole) myocardial perfusion imaging in patients with permanent electronic ventricular pacemakers. METHODS AND RESULTS: Between October 1986 and December 1995, 93 patients with pacemakers underwent pharmacologic stress testing with myocardial perfusion single photon emission computed tomography imaging. Follow-up information on 91 patients (98%) was obtained. Mean follow-up was 5.6 +/- 2.4 years. Previously published clinical and image variables were analyzed for their prognostic significance with regard to cardiac death, cardiac death/nonfatal myocardial infarction, and cardiac death/nonfatal myocardial infarction/late revascularization. The presence of a high-risk scan was a significant predictor of subsequent cardiac death by both univariate (chi 2 = 9.4, P < .001) and multivariate analysis (chi 2 = 6.5, P = .01) after adjustment for clinical score. Clinical score was not a significant predictor of cardiac death. CONCLUSION: This study demonstrates that pharmacologic stress myocardial perfusion imaging provides significant prognostic information in patients with permanent pacemakers. In this population, pharmacologic stress myocardial perfusion imaging can differentiate patients at high risk of a subsequent cardiac event from those at low risk. These results support the American College of Cardiology/American Heart Association guideline recommendations for pharmacologic stress perfusion imaging in patients with permanent pacemakers.