Lara F. Nhola

Detection of Carotid Atherosclerotic Plaque Neovascularization Using Contrast Enhanced Ultrasound: A Systematic Review and Meta-Analysis of Diagnostic Accuracy Studies

BACKGROUND Intraplaque neovascularization is considered an important indicator of plaque vulnerability. Contrast-enhanced ultrasound (CEUS) of carotid arteries improves imaging of carotid intima-media thickness and permits real-time visualization of neovascularization of the atherosclerotic plaque. The authors conducted a systematic review and meta-analysis to evaluate the accuracy of CEUS-detected carotid atherosclerotic plaque. METHODS A systematic search was performed to identify studies published in the MEDLINE, Embase, Scopus, and Web of Science databases from 2004 to June 2015. Studies evaluating the accuracy of quantitative analysis and qualitative analysis (visual interpretation) for the diagnosis of intraplaque neovascularization compared with histologic specimens and/or clinical diagnosis of symptomatic plaque were included. Parameters evaluated were plaque quantitative CEUS intensity and the visual grading of plaque CEUS. A random-effects meta-analysis was used to pool the likelihood ratios (LRs), diagnostic odds ratios, and summary receiver operating characteristic curves. Corresponding areas under the curves were calculated. RESULTS The literature search identified 203 studies, 20 of which were selected for systematic review; the final meta-analysis included seven studies. For qualitative CEUS, pooled sensitivity was 0.80 (95% CI, 0.72-0.87), pooled specificity was 0.83 (95% CI, 0.76-0.89), the pooled positive LR was 3.22 (95% CI, 1.67-6.18), the pooled negative LR was 0.24 (95% CI, 0.09-0.64), the pooled diagnostic odds ratio was 15.57 (95% CI, 4.94-49.03), and area under the curve was 0.894. For quantitative CEUS, pooled sensitivity was 0.77 (95% CI, 0.71-0.83), pooled specificity was 0.68 (95% CI, 0.62-0.73), the pooled positive LR was 2.34 (95% CI, 1.69-3.23), the pooled negative LR was 0.34 (95% CI, 0.25-0.47), the pooled diagnostic odds ratio was 7.06 (95% CI, 3.6-13.82), and area under the curve was 0.888. CONCLUSIONS CEUS is a promising noninvasive diagnostic modality for detecting intraplaque neovascularization. Standardization of quantitative analysis and visual grading classification is needed to increase reliability and reduce technical heterogeneity.

Relationship between HgbA1c and Myocardial Blood Flow Reserve in Patients with Type 2 Diabetes Mellitus: Noninvasive Assessment Using Real-Time Myocardial Perfusion Echocardiography

To study the relationship between glycosylated hemoglobin (HgbA1c) and myocardial perfusion in type 2 diabetes mellitus (T2DM) patients, we prospectively enrolled 24 patients with known or suspected coronary artery disease (CAD) who underwent adenosine stress by real-time myocardial perfusion echocardiography (RTMPE). HgbA1c was measured at time of RTMPE. Microbubble velocity (β min−1), myocardial blood flow (MBF, mL/min/g), and myocardial blood flow reserve (MBFR) were quantified. Quantitative MCE analysis was feasible in all patients (272/384 segments, 71%). Those with HgbA1c > 7.1% had significantly lower β reserve and MBFR than those with HgbA1c ≤ 7.1% (P < 0.05). In patients with suspected CAD, there was a significant inverse correlation between MBFR and HgbA1c (r = −0.279, P = 0.01); however, in those with known CAD, this relationship was not significant (r = −0.117, P = 0.129). Using a MBFR cutoff value > 2 as normal, HgbA1c > 7.1% significantly increased the risk for abnormal MBFR, (adjusted odds ratio: 1.92, 95% CI: 1.12–3.35, P = 0.02). Optimal glycemic control is associated with preservation of MBFR as determined by RTMPE, in T2DM patients at risk for CAD.

Regadenoson Stress Real-Time Myocardial Perfusion Echocardiography for Detection of Coronary Artery Disease: Feasibility and Accuracy of Two Different Ultrasound Contrast Agents

BACKGROUND The aim of this study was to compare the efficacy of myocardial perfusion (MP) and wall motion (WM) analysis obtained with real-time myocardial contrast echocardiography (RTMCE) and two widely used contrast agents in detecting coronary artery disease after injection of the vasodilator regadenoson. METHODS One hundred fifty patients were studied at two academic centers using regadenoson (400-μg intravenous bolus) vasodilator stress RTMCE (7.5% Optison infusion [n = 50] or 1.5% Definity infusion [n = 100]). Both MP and WM with RTMCE were analyzed at rest and after regadenoson bolus. Comparisons of WM and MP sensitivity, specificity, and accuracy were made. Quantitative angiography was performed in all patients within 1 month of the regadenoson stress study (>50% and >70% diameter stenosis was considered significant). Reviewers were blinded to all clinical and quantitative angiographic data. RESULTS Rate-pressure product after regadenoson was higher in Optison than Definity patients (P = .004). Using a 50% diameter stenosis on quantitative angiography as a reference standard, overall sensitivity, specificity, and accuracy for combined WM and MP analysis were not different for both agents (Optison, 77%, 64%, and 73%; Definity, 80%, 74%, and 78%; P = NS). The sensitivity, specificity, and accuracy of WM analysis alone for Optison were 68%, 71%, and 69% compared with 60%, 72%, and 66% for Definity (P = NS). Adding MP analysis improved the sensitivity and accuracy of Definity for detecting both >50% and >70% stenoses (P < .001 vs WM), while MP analysis did not improve the sensitivity of Optison for detecting either >50 or >70% stenoses. CONCLUSIONS RTMCE during regadenoson stress using either Optison or Definity is a rapid and effective method for the detection of coronary artery disease. The ability of MP imaging to improve WM accuracy may depend on the rate-pressure product achieved.

Relationship between glycosylated hemoglobin A1c and coronary flow reserve in patients with Type 2 diabetes mellitus

Type 2 diabetes mellitus patients are at increased risk for macrovascular and microvascular complications. Both in vivo and in vitro studies of small arteries and arterioles of diabetic subjects demonstrate impaired endothelial function without anatomic lesions. Coronary flow reserve (CFR) is a surrogate marker of coronary microcirculatory endothelial function in diabetic patients without significant stenosis of the associated epicardial coronary artery. Glycosylated hemoglobin A1c is related to likelihood of occurrence of microvascular events. The objective of this article is to report on recent developments in multiple noninvasive techniques to assess CFR and their use in aiding the understanding of the relationship of CFR, glycemic control and cardiovascular outcomes.

Incidence, Diagnosis, and Treatment of Cardiac Toxicity From Trastuzumab in Patients With Breast Cancer

Purpose of ReviewTreatment with trastuzumab is a cornerstone of human epidermal growth factor receptor 2 (HER2)-overexpressing breast cancer treatment, but carries an unfortunate risk of toxicity to the cardiovascular system. Here, we review recent findings on trastuzumab-associated cardiotoxicity, focusing on its incidence, diagnosis, and treatment.Recent FindingsScreening with multigated acquisition scan (MUGA) or echocardiogram (ECHO) is recommended to assess cardiac function prior to and during trastuzumab therapy. Because trastuzumab-induced cardiotoxicity is typically reversible, cessation of trastuzumab and/or administration of first-line heart failure agents effectively restores cardiac function in most cases. Severe trastuzumab-induced cardiotoxicity is rare enough that the risk-benefit ratio still weighs in favor of its use in the vast majority of patients with HER2+ breast cancer.SummaryAn improved understanding of the pathophysiology underlying trastuzumab-induced cardiotoxicity and the identification of patients at highest risk will allow us to continue to safely administer trastuzumab in patients with breast cancer.

Cardiovascular Toxicities of Small Molecule Tyrosine Kinase Inhibitors: An Opportunity for Systems-Based Approaches.

Once universally considered a rapidly fatal condition, cancer has increasingly become a chronic medical condition and comorbidities and adverse effects of cancer therapies have become increasingly significant. One of the leading advancements that has gained traction for the treatment of a variety of malignancies is the class of small molecule tyrosine kinase inhibitors (TKIs). Although, in many aspects revolutionary, TKIs have their own profile of side effects, including cardiovascular side effects, the most common being hypertension (HTN), congestive heart failure, corrected QT (QTc) prolongation, and instances of premature coronary heart disease. Herein, we describe the mechanisms of small TKI‐induced cardiovascular toxicity and related intracellular signaling. In particular, systems‐based approaches to the understanding of small TKI‐induced cardiovascular toxicity are addressed. The pathophysiology of synergic cardiovascular toxicity from TKIs, anthracyclines, and monoclonal antibodies (e.g., trastuzumab, bevacizumab) is illustrated. Finally, recommendations are made for implementing systems medicine in clinical practice, for individualized cardiovascular wellness after cancer therapy.

Cardiovascular Toxicities of Small Molecule TKIs: An Opportunity for Systems-Based Approaches

Once universally considered a rapidly fatal condition, cancer has increasingly become a chronic medical condition and comorbidities and adverse effects of cancer therapies have become increasingly significant. One of the leading advancements that has gained traction for the treatment of a variety of malignancies is the class of small molecule tyrosine kinase inhibitors (TKIs). Although, in many aspects revolutionary, TKIs have their own profile of side effects, including cardiovascular side effects, the most common being hypertension (HTN), congestive heart failure, corrected QT (QTc) prolongation, and instances of premature coronary heart disease. Herein, we describe the mechanisms of small TKI‐induced cardiovascular toxicity and related intracellular signaling. In particular, systems‐based approaches to the understanding of small TKI‐induced cardiovascular toxicity are addressed. The pathophysiology of synergic cardiovascular toxicity from TKIs, anthracyclines, and monoclonal antibodies (e.g., trastuzumab, bevacizumab) is illustrated. Finally, recommendations are made for implementing systems medicine in clinical practice, for individualized cardiovascular wellness after cancer therapy.

Rationale for Cardio-Oncology Units

With the rapidly rising number of patients surviving cancer, often in the setting of new or pre-existing cardiovascular disease and risk factors, a need has arisen for a specialty within the realm of cardiovascular care that can evaluate and manage these patients along with our colleagues in oncology and hematology. By the same token, all health care providers involved in the care of cancer patients with heart disease must be fully aware of the impact of adverse cardiovascular effects on the survival of these patients. Collaboration is required to mitigate the effect of cardiovascular toxicity associated with these necessary life-saving cancer therapies. The cardio-oncologist plays a pivotal role in bridging the 2 specialties, by creating a comprehensive plan to address the comorbidities as well as to provide guidance on the optimal choice of therapy. In this 3-part review, we will outline: a) the significant impact of cancer therapies on the cardiovascular health of patients with cancer and cancer survivors, b) the advantage of a multidisciplinary team in addressing these cardiovascular complications, and c) the delivery of clinical care to patients with cancer and heart disease.

A comparison of infarct mass by cardiac magnetic resonance and real time myocardial perfusion echocardiography as predictors of major adverse cardiac events following reperfusion for ST elevation myocardial infarction.

Infarct mass as assessed by myocardial‐delayed enhancement imaging on cardiac magnetic resonance (CMR) and myocardial blood flow as assessed by real time myocardial perfusion echocardiography (RT‐MPE) have been shown to predict adverse events following ST elevation myocardial infarction (STEMI). There has been no published comparison of quantitative assessment using these modalities as predictors of clinical outcomes to date. We compared RT‐MPE with CMR for prediction of cardiac events in reperfused STEMI patients.

RELATIONSHIP BETWEEN HBA1C AND CORONARY FLOW RESERVE IN PATIENTS WITH TYPE 2 DIABETES MELLITUS: A REAL-TIME MYOCARDIAL CONTRAST ECHOCARDIOGRAPHY STUDY

We examined the relationship between glycosylated hemoglobin (HbA1c) and coronary flow reserve (CFR) in type 2 diabetes mellitus (DM) pts using real-time myocardial contrast echocardiography (RTMCE). We prospectively enrolled 24 pts (16 male; 66±12 yrs, DM duration 8±6 yrs, 42% smokers, 83% HTN,