Comparison of Echocardiography and Multi-Planar Gated Acquisition Scans for Predicting Cancer-Treatment-Related Cardiovascular Dysfunction.

BACKGROUND: Current guidelines recommend using sequential cardiac imaging to monitor for cancer treatment-related cardiac dysfunction (CTRCD) in patients undergoing potentially cardiotoxic chemotherapy. Multiple different imaging cardiac modalities are available and there are few prospective head-to-head comparative studies to help guide treatment. OBJECTIVES: To perform an exploratory prospective cohort study of "real-world" CTRCD comparing multigated acquisition nuclear ventriculography (MUGA) at the referring cancer specialist's discretion with a novel echocardiographic strategy at an Australian tertiary hospital. METHOD: Patients were recruited from haematology and oncology outpatient clinics if they were scheduled for treatment with anthracyclines and/or trastuzumab. Patients underwent simultaneous MUGA-based cardiac imaging (conventional strategy) at a frequency according to evidenced-based guidelines in addition to researcher-conducted echocardiographic imaging. The echocardiographic imaging was performed in all patients at time points recommended by international society guidelines. Outcomes included adherence to guideline recommendations, concordance between MUGA and echocardiographic left ventricular ejection fraction (LVEF) measurements, and detection of cardiac dysfunction (defined as >5% LVEF decrement from baseline by three-dimensional [3D]-LVEF). A secondary end point was accuracy of global longitudinal strain in predicting cardiac dysfunction. RESULTS: In total, 35 patients were recruited, including 15 with breast cancer, 19 with haematological malignancy, and one with gastric cancer. MUGA and echocardiographic LVEF measurements correlated poorly with limits of agreement of 30% between 3D-LVEF and MUGA-LVEF and 37% for 3D-LVEF and MUGA-LVEF. Only one case (2.9%) of CTRCD was diagnosed by MUGA, compared with 12 (34.2%) cases by echocardiography. Four (4) patients had >10% decrement in 3D-LVEF that was not detected by MUGA. Global longitudinal strain at 2 months displayed significant ability to predict CTRCD (area under the curve, 0.75, 95% confidence interval, 0.55-0.94). CONCLUSIONS: The MUGA correlates poorly with echocardiographic assessment with substantial discrepancy between MUGA and echocardiography in CTRCD diagnosis. Echocardiographic and MUGA imaging strategies should not be considered equivalent for imaging cancer patients, and a single imaging modality should ideally be used per patient to prevent misdiagnosis by inter-modality variation These findings should be considered hypothesis-generating and require confirmation with larger studies.

Cost-effectiveness of combined catheter ablation and left atrial appendage closure for symptomatic atrial fibrillation in patients with high stroke and bleeding risk.

BACKGROUND: Combined catheter ablation (CA) and left atrial appendage closure (LAAC) have been proposed for management of symptomatic atrial fibrillation (AF) in patients with high stroke and bleeding risk. We assessed the cost-effectiveness of combined CA and LAAC compared with CA and standard oral anticoagulation (OAC) in symptomatic AF. METHODS: A Markov model was developed to assess total costs, quality-adjusted life-years (QALYs), and the incremental cost-effectiveness ratio among 2 post-CA strategies: (1) standard OAC and (2) LAAC (combined CA and LAAC procedure). The base-case used a 10-year time horizon and consisted of a hypothetical cohort of patients aged 65 years with symptomatic AF, with high thrombotic (CHA2DS2-VASc = 3) and bleeding risk (HAS-BLED = 3), and planned for AF ablation. Values for transition probabilities, utilities, and costs were derived from the literature. Costs were converted to 2020 US dollars. Half-cycle correction was applied, and costs and QALYs were discounted at 3% annually. Sensitivity analyses were performed for significant variables and scenario analyses for higher embolic risk. RESULTS: In the base-case cohort of 10,000 patients followed for 10 years, total costs for the LAAC strategy were $29,027 and for OAC strategy were $27,896. The LAAC strategy was associated with 122 fewer disabling strokes and 203 fewer intracranial hemorrhages per 10,000 patients compared with the OAC strategy. The LAAC strategy had an incremental cost-effectiveness ratio of $11,072/QALY. In sensitivity analyses, although cost-effectiveness was highly dependent on the risk of intracranial hemorrhage in the LAAC strategy and the cost of the combined procedure, LAAC was superior to OAC under the most circumstances. Scenario analyses demonstrated that the combined procedure was more cost-effective in patients with higher stroke risk. CONCLUSIONS: In symptomatic AF patients with high stroke and bleeding risk who are planned for CA, the combined CA and LAAC procedure may be a cost-effective therapeutic option and be more beneficial to patients with CHA2DS2-VASc risk score ≥3.

An emerging epidemic: cancer and heart failure.

Heart disease and cancer are the two leading causes of mortality globally. Cardiovascular complications of cancer therapy significantly contribute to the global burden of cardiovascular disease. Heart failure (HF) in particular is a relatively common and life-threatening complication. The increased risk is driven by the shared risk factors for cancer and HF, the direct impact of cancer therapy on the heart, an existing care gap in the cardiac care of patients with cancer and the increasing population of adult cancer survivors. The clear relationship between cancer treatment initiation and the potential for myocardial injury makes this population attractive for prevention strategies, targeted cardiovascular monitoring and treatment. However, there is currently no consensus on the optimal strategy for managing this at-risk population. Uniform treatment using cardioprotective medications may reduce the incidence of HF, but would impose frequently unnecessary and burdensome side effects. Ideally we could use validated risk-prediction models to target HF-preventive strategies, but currently no such models exist. In the present review, we focus on evidence and rationales for contemporary clinical decision-making in this novel field and discuss issues, including the burden of HF in patients with cancer, the reasons for the elevated risk and potential prevention strategies.

Novel Non-pharmaceutical Advancements in Heart Failure Management: The Emerging Role of Technology.

PURPOSE OF REVIEW: To summarise and discuss the implications of recent technological advances in heart failure care. RECENT FINDINGS: Heart failure remains a significant source of morbidity and mortality in the US population despite multiple classes of approved pharmacological treatments. Novel cardiac devices and technologies may offer an opportunity to improve outcomes. Baroreflex Activation Therapy and Cardiac Contractility Remodelling may improve myocardial contractility by altering neurohormonal stimulation of the heart. Implantable Pulmonary Artery Monitors and Biatrial Shunts may prevent heart failure admissions by altering the trajectory of progressive congestion. Phrenic Nerve Stimulation offers potentially effective treatment for comorbid conditions. Smartphone applications offer an intriguing strategy for improving medication adherence. SUMMARY: Novel heart failure technologies offer promise for reducing this public health burden. Randomized controlled studies are indicated for assessing the future role of these novel therapies.

Automated Quantification in Echocardiography.

Echocardiography remains the predominant modality for cardiac imaging. Recent technological advances have led to the availability of new echocardiographic techniques for more accurate quantification of volumes, function, myocardial mechanics, and valvular heart disease. However, in our opinion, the real-world clinical uptake of these techniques has been poor due to limited awareness and familiarity, associated time burden, and issues of variability. Automation represents a potential solution to these issues and has already made routine myocardial strain measurements and 2- and 3-dimensional left ventricular ejection fraction measurements a clinical reality. Further enhancements in automation and data in understudied populations are likely to assist in the uptake of these new quantitative echocardiographic techniques in routine clinical practice. This review discusses current automated quantification techniques in echocardiography and their limitations and describes how these techniques can be incorporated into echocardiography laboratories.

Normal Ranges of Left Atrial Strain by Speckle-Tracking Echocardiography: A Systematic Review and Meta-Analysis.

BACKGROUND: Recent advances in the assessment of myocardial function have facilitated the direct measurement of atrial function using speckle-tracking echocardiography. Currently, normal reference ranges for atrial function using speckle-tracking echocardiography are based on a few initial studies, with variations among modestly sized (n = 100-350) studies. METHODS: The authors searched the PubMed, Embase, and Scopus databases for the key terms "left atrial/atrial/atrium" and "strain/function/deformation/stiffness" and "speckle tracking/Velocity Vector Imaging/edge tracking." Studies of global left atrial function using speckle-tracking were selected if they involved >30 normal or healthy participants without any cardiac risk factors. Normal ranges for reservoir strain, conduit strain, and contractile strain were computed using a random-effects model. Meta-regression and subgroup analysis was performed to explore between-study heterogeneity. RESULTS: Forty studies (2,542 healthy subjects) satisfied the inclusion criteria. Meta-analysis revealed a normal reference range for reservoir strain of 39% (95% CI, 38%-41%, from 40 articles), for conduit strain of 23% (95% CI, 21%-25%, from 14 articles), and for contractile strain of 17% (95% CI, 16%-19%, from 18 articles). Meta-regression identified heart rate (P = .02) and body surface area (P = .003) as contributors to this heterogeneity. Subgroup analyses revealed heterogeneity due to sample size (n > 100 vs N < 100, P = .02). CONCLUSIONS: The normal reference ranges for the three components of left atrial function are demonstrated. The between-study heterogeneity is explained partly by heart rate, body surface area, and sample size.

Long-term Risk of Heart Failure and Myocardial Dysfunction After Thoracic Radiotherapy: A Systematic Review.

BACKGROUND: Chest irradiation is a commonly used treatment for malignancy, with demonstrated symptomatic and survival benefit. The frequency and presentation of cardiovascular complications of radiotherapy remains unclear. METHODS: We performed a systematic review to evaluate the prevalence and manifestations of myocardial dysfunction (asymptomatic and symptomatic) in long-term cancer survivors treated with radiotherapy. RESULTS: Thoracic radiotherapy is associated with increased risk of heart failure in long-term follow-up, with hazard ratios ranging from 2.7 to 7.4 for Hodgkin lymphoma, and 1.5-2.4 for breast cancer. Although ejection fraction is often normal, systolic dysfunction has been more widely reported with modern techniques including 2-dimensional speckle strain and cardiac magnetic resonance. This might have implications for the selection of patients for cardioprotection. Despite common emphasis, diastolic functional abnormalities were infrequent in the long term. A limited amount of data suggest that right ventricular dysfunction is important in this population. CONCLUSIONS: The reports were heterogeneous, used different treatments, end points, and definitions of myocardial dysfunction, and most studies on the cardiac consequences of radiotherapy involved small numbers of patients and were published decades ago, making it difficult to formulate definitive conclusions for the current era.

Routine Prophylactic Cardioprotective Therapy Should Be Given to All Recipients at Risk of Cardiotoxicity From Cancer Chemotherapy.

The inevitability of cardiac injury in many patients treated for cancer mandates strategies to mitigate the effect of cancer treatment on the heart. In this article we argue that the best approach to prevent cardiotoxicity is universal primary prevention for everyone at risk for irreversible myocardial injury. Our viewpoint is on the basis of 5 major arguments that we discuss in detail in this article. We outline the shortcomings of alternate strategies for prevention and highlight that the strongest existing evidence today supports our viewpoint. In particular, data from multiple randomized controlled trials indicate that most patients who receive anthracyclines are at risk, and should be accordingly considered for primary prevention.

Meta-Analysis of Association Between Mediastinal Radiotherapy and Long-Term Heart Failure.

This investigation sought to identify and quantify any increased risk of long-term heart failure (HF) after thoracic radiotherapy (RT) for cancer and identify any population covariates that corresponded with increased risk. Electronic databases were systematically searched for studies reporting relative risk, odds ratio, and hazard ratio (HR) for symptomatic HF more than 5 years after RT administration. Clinical characteristics, study design, univariable effect sizes, and associated 95% CIs were extracted. Univariable effect size was pooled and computed in a meta-analysis using random-effects model weighted by inverse variance. Six studies (45,669 patients) with weighted median follow-up duration of 13.9 years were included, each data-linkage study that reported HRs for HF. Pooled HR for long-term HF was significant (HR 1.83 [1.09 to 3.08], p = 0.022), with significant between-study heterogeneity (Q 43.38, df = 5, p <0.001, I2 88.47%). Statistical significance was lost when excluding studies of malignancies other than breast cancer or hematological malignancies and excluding studies with Newcastle-Ottawa scores <8, but the direction of effect and magnitude remained approximately the same. Subgroup and meta-regression analyses demonstrated that study differences in age at time of RT administration and duration of follow-up explained approximately 80% of observed heterogeneity. Earlier publication date was associated with increased HF risk. Other variables, including female proportion, proportion of adjuvant chemotherapy use, and sample size did not significantly impact the conclusions. In conclusion, RT approximately doubled the long-term risk of HF. This finding was associated with younger age at time of RT and longer follow-up duration, which explained approximately 80% of interstudy heterogeneity.

Cost-effectiveness of strain-targeted cardioprotection for prevention of chemotherapy-induced cardiotoxicity.

BACKGROUND: Cancer chemotherapy increases the risk of heart failure. This cost-effectiveness model compared strain-guided cardioprotection with other protective strategies using a health care payer perspective and five-year time horizon. METHODS: Three cardioprotection strategies were assessed: 1) usual care (EF-guided cardioprotection, EFGCP) with cardioprotection initiated on diagnosis of LVEF-defined cardiotoxicity (EF-CTX), 2) universal cardioprotection (UCP) for all such patients, and 3) strain-guided cardioprotection (SGCP - treatment of patients with subclinical cardiotoxicity [S-CTX]). A Markov model, informed by the published literature on transitional probabilities, costs and quality-adjusted life years (QALYs) was developed to assess the incremental cost-effectiveness ratio (ICER). Costs, effects and ICER of each specified cardioprotective strategy were assessed over a 5-year range, with sensitivity analyses for significant variables. RESULTS: In the reference case of a 49year old woman with stage IIb breast cancer treated with sequential anthracyclines and trastuzumab, strain-guided cardioprotection (3.79 QALYS and $4159 cost over 5years) dominated both UCP (3.64 QALYs and $5967 cost over 5years) and EFGCP (3.53 QALYs and $7033 cost over five years). Model results were dependent on the probabilities of patients developing subclinical LV dysfunction, with UCP dominating alternative strategies at probabilities ≥51%. Variations in the cost of cardioprotective medications and probabilities of cardioprotection side-effects had no effect on model conclusions. CONCLUSIONS: In patients at risk of chemotherapy-related cardiotoxicity, strain-guided cardioprotection provides more QALYs at lower cost than standard care or uniform cardioprotection.

Importance of Calibration Method in Central Blood Pressure for Cardiac Structural Abnormalities.

BACKGROUND: Central blood pressure (CBP) independently predicts cardiovascular risk, but calibration methods may affect accuracy of central systolic blood pressure (CSBP). Standard central systolic blood pressure (Stan-CSBP) from peripheral waveforms is usually derived with calibration using brachial SBP and diastolic BP (DBP). However, calibration using oscillometric mean arterial pressure (MAP) and DBP (MAP-CSBP) is purported to provide more accurate representation of true invasive CSBP. This study sought to determine which derived CSBP could more accurately discriminate cardiac structural abnormalities. METHODS: A total of 349 community-based patients with risk factors (71±5years, 161 males) had CSBP measured by brachial oscillometry (Mobil-O-Graph, IEM GmbH, Stolberg, Germany) using 2 calibration methods: MAP-CSBP and Stan-CSBP. Left ventricular hypertrophy (LVH) and left atrial dilatation (LAD) were measured based on standard guidelines. RESULTS: MAP-CSBP was higher than Stan-CSBP (149±20 vs. 128±15mm Hg, P < 0.0001). Although they were modestly correlated (rho = 0.74, P < 0.001), the Bland-Altman plot demonstrated a large bias (21mm Hg) and limits of agreement (24mm Hg). In receiver operating characteristic (ROC) curve analyses, MAP-CSBP significantly better discriminated LVH compared with Stan-CSBP (area under the curve (AUC) 0.66 vs. 0.59, P = 0.0063) and brachial SBP (0.62, P = 0.027). Continuous net reclassification improvement (NRI) (P < 0.001) and integrated discrimination improvement (IDI) (P < 0.001) corroborated superior discrimination of LVH by MAP-CSBP. Similarly, MAP-CSBP better distinguished LAD than Stan-CSBP (AUC 0.63 vs. 0.56, P = 0.005) and conventional brachial SBP (0.58, P = 0.006), whereas Stan-CSBP provided no better discrimination than conventional brachial BP (P = 0.09). CONCLUSIONS: CSBP is calibration dependent and when oscillometric MAP and DBP are used, the derived CSBP is a better discriminator for cardiac structural abnormalities.