Early detection of cancer therapy cardiotoxicity by radionuclide angiography: An update.

Cancer therapy-induced cardiotoxicity is an emerging clinical and healthcare issue. Myocardial dysfunction and heart failure are mostly responsible for increased cardiovascular mortality in cancer disease survivors. Several imaging surveillance techniques have been proposed for early diagnosis of cancer therapy-induced cardiac dysfunction. Our aim was to provide an update of radionuclide angiography applications in this field. Radionuclide angiography is widely used to assess left ventricular ejection fraction (LVEF) throughout cancer treatment, especially in patients with limited acoustic window. Additional prognostic data may be provided by phase analysis and diastolic function evaluation. Low LVEF and high approximate entropy at baseline seem to be predictors for cancer therapy-induced cardiac dysfunction. A decrease in peak filling rate and/or an increase in time to peak filling rate may be observed in patients undergoing anthracycline and/or trastuzumab administration. Diastolic function impairment may precede or not LVEF decrease. In conclusion, recent studies have provided novel insights into the possible role of radionuclide angiography in the early detection of cancer therapy cardiotoxicity. While interpreting the results of a radionuclide angiography examination, an integrated approach combining the evaluation of LVEF, LV diastolic function, and phase analysis may be useful to improve risk stratification of cancer patients treated with cardiotoxic agents.

Equilibrium radionuclide angiography: Intra- and inter-observer repeatability and reproducibility in the assessment of cardiac systolic and diastolic function.

BACKGROUND: This study aimed to assess intra- and inter-observer agreement in assessing the systolic and diastolic function with equilibrium radionuclide angiography (ERNA). MATERIALS AND METHODS: Thirty-two adults underwent baseline and repeat ERNA. An experienced and a trainee operator analyzed the data by assigning regions of interest manually, fully automatically, and semi-automatically. The Bland-Altman statistic (mean ± 1.96 standard deviations of the differences) was used to assess the repeatability (two different assessments of a single acquisition) and reproducibility (assessments of two different acquisitions). RESULTS: Using the semi-automated technique the intraobserver repeatability and reproducibility of left ventricular ejection fraction for the experienced physician were - 0.1 ± 3.7 and 0.0 ± 3.8 and for the trainee 2.2 ± 10.6 and 1.9 ± 8.4, respectively. The inter-observer repeatability and reproducibility were - 1.8 ± 6.4 and 0.4 ± 9.0, respectively. Among the parameters of diastolic function, the intraobserver repeatability and reproducibility of the peak filling rate for the experienced physician were - 0.0 ± 1.1 and - 0.1 ± 1.1 and for the trainee 0.2 ± 3.5 and 0.4 ± 3.7, respectively. The inter-observer repeatability and reproducibility were 0.3 ± 1.5 and 0.5 ± 4.0, respectively. Similar was the pattern for the other diastolic indices. In all cases the limits of agreement varied according to the quantification approach. CONCLUSION: A good repeatability but a moderate reproducibility was found in the assessment of the LVEF. Less good were the findings in the assessment of diastolic function.

Necessity of routine cardiac evaluation in patients receiving pegylated liposomal doxorubicin for gynecologic cancer.

OBJECTIVE: Pegylated liposomal doxorubicin (PLD) has similar reported clinical efficacy compared with conventional doxorubicin with less cardiotoxicity. The manufacturer of PLD advises that cardiac function should be evaluated with endomyocardial biopsy, echocardiography or multigated radionucleotide scan (MUGA) pre-treatment and during therapy. This study was designed to assess the necessity of pre-treatment cardiac evaluation in patients receiving PLD. METHODS: After IRB approval, a retrospective study of all women with gynecologic cancer who received PLD from 2006 to 2018 was performed. Demographic information, treatment records, cardiac risk factors, and cardiac surveillance testing were examined. Wilcoxon signed rank sum test and logistic regression were used to evaluate the association of cumulative PLD exposure with cardiotoxicity. RESULTS: A total of 235 patients received PLD for gynecologic cancer. Patients received a median of 3 cycles of PLD with a cumulative dosage of 237 mg over a median follow-up time of 24 months. Sixteen patients in the cohort (7%) had no cardiac surveillance at all. Of the remaining patients who underwent cardiac testing, 183 (84%) received MUGA scans and 36 (16%) had echocardiography. Of the 56 patients who had both pre- and post-treatment cardiac testing, there was no significant difference in median ejection fraction (p = 0.17). Three patients developed PLD-associated cardiac toxicity but only one patient had severe manifestations requiring discontinuation of PLD therapy. CONCLUSIONS: Routine cardiac testing before, during or after treatment with PLD may be unnecessary. Cardiac testing may be more appropriate for individual patients for whom the clinical suspicion of PLD-related cardiac toxicity is high.

Effects of cardiac resynchronization therapy on right ventricular function during rest and exercise, as assessed by radionuclide angiography, and on NT-proBNP levels.

AIM: We carried out this study to investigate mid-term effects of cardiac resynchronization therapy (CRT) on right ventricular (RV) function and neurohormonal response, expressed by N-terminal pro-brain natriuretic peptide (NT-proBNP), in heart failure patients stratified by baseline RV ejection fraction (RVEF). METHODS AND RESULTS: Thirty-six patients with nonischemic dilated cardiomyopathy underwent technetium-99m radionuclide angiography with bicycle exercise immediately after CRT implantation (during spontaneous rhythm and after CRT activation) and 3 months later. Plasma NT proBNP was assessed before implantation and after 3 months. At baseline, RVEF was impaired (≤35%) in 14 patients, preserved (>35%) in 22. At 3 months, RVEF improved during rest and exercise (P = .02) in patients with impaired RV function, while remaining unchanged in patients with preserved RV function. Rest and exercise RV dyssynchrony decreased in both groups at follow-up (P < .05). A similar mid-term improvement in left ventricular (LV) function and NT-proBNP was observed in patients with impaired and preserved RVEF. In the former, the decrease in NT-proBNP correlated with the improvements both in LV and RV dyssynchrony and functions. CONCLUSION: CRT may improve RV performance, during rest and exercise, and neurohormonal response in heart failure patients with nonischemic dilated cardiomyopathy and baseline RV dysfunction. RV dysfunction should not be considered per se a primary criterion for excluding candidacy to CRT.

Left ventricular ejection fraction determined with the simulation of a very low-dose CZT-SPECT protocol and an additional count-calibration on planar radionuclide angiographic data.

PURPOSE: To determine whether the left ventricular ejection fractions (EFs), measured on a high-sensitivity CZT single photon emission computed tomography (SPECT)-camera with a 70% reduction in recording times and a prevention of EF overestimation through an additional count-calibration, are concordant with reference EF from planar radionuclide angiography (2D-RNA). METHODS: An additional 10-minute CZT-SPECT recording was performed in patients referred to 2D-RNA for cardiomyopathy (n = 23) or chemotherapy monitoring (n = 50) with an in vivo red blood cell labeling with 850 MBq [Formula: see text]. The EF, obtained from CZT-SPECT with 100% (SPECT100) or 30% (SPECT30) projection times and with a SPECT-count calibration on the 2D-RNA counts of corresponding cavity volumes, were compared to EF from 2D-RNA. RESULTS: Strong and equivalent relationships were documented between the EF from 2D-RNA and the calibrated EF from SPECT100 (y = 0.89x + 6.62; R2 = 0.87) and SPECT30 (y = 0.87x + 8.40; R2 = 0.85), and the mean EF from SPECT100 (54% ± 15%) and SPECT30 (53% ± 16%) were close to that from 2D-RNA (55% ± 15%). However, upward shifts in these mean values were documented in the absence of count calibration for both SPECT100 (60% ± 18%) and SPECT30 (60% ± 18%). CONCLUSION: Left ventricular EF may be determined on a high-sensitivity CZT-camera, a 70% reduction in injected activities, and an additional count-calibration for further enhancing the concordance with 2D-RNA values.

Radiosynoviorthesis in hemophilic arthropathy: pathologic blood pool imaging on pre-therapeutic bone scintigraphy is not a predictor of treatment success.

PURPOSE: Increased articular 99mTc MDP uptake on blood pool imaging (BPI) of patients with rheumatologic conditions is indicative of active inflammatory changes, and has been suggested as a strong predictor of response to radiosynoviorthesis (RSO). In this study, we aimed to assess the value of pretreatment BPI positivity (i.e. scintigraphic-apparent hyperemia) for successful RSO in hemophilic arthropathy. METHODS: Thirty-four male patients with painful hemophilic arthropathy underwent RSO after failure of conservative treatment. Treated joints comprised the knee in eight, elbow in five, and ankle in 21 patients. Pretreatment triple-phase bone scintigraphy showed hyperemic joints (pathologic BPI) in 17 patients, whereas 17 patients had no increased tracer uptake on BPI. Response to RSO was evaluated 6 months post-treatment by measuring changes in intensity of arthralgia according to the visual analog scale (VAS), bleeding frequency, and range of motion. The association between hyperemia (pathologic BPI) and treatment outcome was examined using nonparametric tests for independent samples. RESULTS: Clinically evident pain relief occurred in 26 patients (76.5 %), and the mean VAS decreased from 7.7 ± 1.1 to 4.6 ± 2.7 (p < 0.001). Joint bleeding frequency (hemarthrosis) decreased from 4.5 ± 0.6 to 2.1 ± 0.4 during the first 6 months after RSO (p < 0.001). For both parameters (pain relief and bleeding frequency), patients experienced a similar benefit from RSO regardless of pretreatment BPI: arthralgia (p = 0.312) and frequency of hemarthrosis (p = 0.396). No significant improvement was observed for range of motion, but it was significantly more restricted in hyperemic joints both before (p = 0.036) and after treatment (p = 0.022). CONCLUSIONS: Hemophilic arthropathy can be effectively treated with RSO regardless of pre-therapeutic BPI. Patients in whom articular hyperemia is not detectable by scintigraphy may have similar (outstanding) outcomes, and thus should not be excluded from treatment.

Comparison of echocardiographic parameters to assess right ventricular function in pulmonary hypertension.

Although measurement of right ventricular ejection fraction (RVEF) may be relevant for evaluation of therapeutic efficacy and/or prognosis in patients with pulmonary hypertension, RVEF obtained by echocardiography has limited accuracy. In contrast, radionuclide and/or magnetic resonance imaging can measure RVEF more reliably. In this study, we investigated the relationship between RVEF measured by radionuclide angiography and the echocardiographic parameters that are recommended by the American Society of Echocardiography as representative of right heart function. There were 23 study participants with pulmonary hypertension who underwent radionuclide angiography and 2-dimensional and Doppler echocardiography (n = 30 measurements). RVEF measured by radionuclide angiography correlated with right ventricular Tei index (RV Tei index) measured by Doppler echocardiography (r = -0.601, P < 0.0005). Receiver operating characteristic curve analysis showed that an RV Tei index cut-off value of 0.371 was the best of predictor of RVEF ≤35% (area under the curve = 0.768, sensitivity = 0.857, selectivity = 0.667). Multiple regression analysis showed that RVEF was correlated with the RV Tei index, and this association was independent of other echocardiographic right ventricular function parameters (r = -0.644, P < 0.005). The RV Tei index measured by Doppler echocardiography may be an acceptable surrogate marker of RVEF in patients with pulmonary hypertension.

[Reliability of venous blood gas analysis and radionuclide angiography in post-traumatic dystrophy]. / Reliabilität der venösen Blutgasanalyse und Radionuklidangiographie bei Posttraumatischer Dystrophie.

BACKGROUND: The diagnosis "post-traumatic dystrophy" (PTD) was first defined with clinical and paraclinical criteria by Scola et al. in 2013. OBJECTIVES: The objectivity and reliability of the paraclinical criteria (venous blood gas analysis [vBGA], radionuclide angiography [RNA]), and recommendations for therapy should be assessed in a prospective study. MATERIALS AND METHODS: In five patients with clinical signs of post-traumatic nonbacterial inflammation of the hand, both diagnosis and a 3­week hospital treatment were carried out in accordance with the publication mentioned above. The primary traumata (four fractures and one soft-tissue injury) were located in either the hand or the forearm. Unsuccessful outpatient treatment always led to hospital admission. One patient with severe osteopenia in the hand skeleton was treated with bisphosphonates for 6 months. RESULTS: All patients fulfilled the clinical and paraclinical criteria for the diagnosis of PTD. On admission, an elevated venous partial pressure of oxygen was found by vBGA in the affected hand (∆pO2 mean 22 ± 3 mm Hg) and a hyperperfusion due to arteriovenous shunts was measured using RNA (mean 75 ± 47%). The symptomatic treatment was extremely well tolerated; by the time of discharge, all patients achieved full functioning of the hand with minor loss of strength (venous ∆pO2 mean 5 ± 3 mm Hg). The osteopenia in the one patient treated with bisphosphonates showed recalcification after 6 months. CONCLUSION: The reliability of clinical and paraclinical criteria for PTD were confirmed. vBGA and RNA seem to be good parameters for confirming the diagnosis of PTD. "Rubor," a symptom traditionally interpreted as "hyperemia," contradicts the paraclinical findings and leads to the assumption that the cause of this post-traumatic syndrome is microvascular dysfunction.

Assessment of left ventricular ejection fraction using low radiation dose computed tomography.

BACKGROUND: Cardiac CT is a non-invasive modality with the ability to estimate LVEF. However, given its limited temporal resolution and radiation, there has been initial resistance to use CT to measure LVEF. Developing an accurate, fast, low radiation dose protocol is desirable. OBJECTIVE: The objective of this study is to demonstrate that a 'low radiation dose' 64 slice cardiac computed tomography (CT) protocol is feasible and can accurately measure left ventricular ejection fraction (LVEF) while delivering a radiation dose lower than radionuclide angiography (RNA). METHODS: Patients undergoing RNA were prospectively screened and enrolled to undergo a 'low-dose' 64 slice CT LVEF protocol. LVEF measures, duration of each study and radiation dose between CT and RNA were compared. RESULTS: A total of 77 patients (mean age = 61.8 ± 12.2 years and 58 men) were analyzed. The mean LVEF measured by CT and RNA were 41.9 ± 15.2% and 39.4 ± 13.9%, respectively, (P = 0.154) with a good correlation (r = 0.863). Bland-Altman plot revealed a good agreement between the CT and RNA LVEF (mean difference of -2.4). There was good agreement between CT LVEF and RNA for identifying patients with LVEF ≤30% (kappa = 0.693) and LVEF ≥50% (kappa = 0.749). The mean dose estimated effective dose for CT and RNA were 4.7 ± 1.6 and 9.5 ± 1.0 mSv, respectively. The mean CT LVEF imaging duration (4:32 ± 3:05 minutes) was significantly shorter than the RNA image acquisition time (9:05 ± 2:36 minutes; p < 0.001). CONCLUSION: The results of our study suggest that low-dose CT LVEF protocol is feasible, accurate, and fast while delivering a lower radiation dose than traditional RNA.

Does diastolic dysfunction precede systolic dysfunction in trastuzumab-induced cardiotoxicity? Assessment with multigated radionuclide angiography (MUGA).

BACKGROUND: Trastuzumab is successfully used for the treatment of HER2-positive breast cancer. Because of its association with cardiotoxicity, LVEF is monitored by MUGA, though this is a relatively late measure of cardiac function. Diastolic dysfunction (DD) is believed to be an early predictor of cardiac impairment. We evaluate the merit of MUGA-derived diastolic function parameters in the early detection of trastuzumab-induced cardiotoxicity (TIC). METHODS AND RESULTS: 77 trastuzumab-treated patients with normal baseline systolic and diastolic function were retrospectively selected (n = 77). All serial MUGA examinations were re-analyzed for systolic and diastolic function parameters. 36 patients (47%) developed SD and 45 patients (58%) DD during treatment. Both systolic and diastolic parameters significantly decreased. Of the patients with SD, 24 (67%) also developed DD. DD developed prior to systolic impairment in 54% of cases, in 42% vice versa, while time to occurrence did not differ significantly (P = .52). This also applied to the subgroup of advanced stage breast cancer patients (P = .1). CONCLUSIONS: Trastzumab-induced SD and DD can be detected by MUGA. An impairment of MUGA-derived diastolic parameters does not occur prior to SD and therefore cannot be used as earlier predictors of TIC.

Recommendations for cardiomyopathy surveillance for survivors of childhood cancer: a report from the International Late Effects of Childhood Cancer Guideline Harmonization Group.

Survivors of childhood cancer treated with anthracycline chemotherapy or chest radiation are at an increased risk of developing congestive heart failure. In this population, congestive heart failure is well recognised as a progressive disorder, with a variable period of asymptomatic cardiomyopathy that precedes signs and symptoms. As a result, several clinical practice guidelines have been developed independently to help with detection and treatment of asymptomatic cardiomyopathy. These guidelines differ with regards to definitions of at-risk populations, surveillance modality and frequency, and recommendations for interventions. Differences between these guidelines could hinder the effective implementation of these recommendations. We report on the results of an international collaboration to harmonise existing cardiomyopathy surveillance recommendations using an evidence-based approach that relied on standardised definitions for outcomes of interest and transparent presentation of the quality of the evidence. The resultant recommendations were graded according to the quality of the evidence and the potential benefit gained from early detection and intervention.

Imaging of systemic vasculitis in childhood.

The term "systemic vasculitis" encompasses a diverse set of diseases linked by the presence of blood-vessel inflammation that are often associated with critical complications. These diseases are uncommon in childhood and are frequently subjected to a delayed diagnosis. Although the diagnosis and treatment may be similar for adult and childhood systemic vasculitides, the prevalence and classification vary according to the age group under investigation. For example, Kawasaki disease affects children while it is rarely encountered in adults. In 2006, the European League Against Rheumatism (EULAR) and the Pediatric Rheumatology European Society (PReS) proposed a classification system for childhood vasculitis adopting the system devised in the Chapel Hill Consensus Conference in 1993, which categorizes vasculitides according to the predominant size of the involved blood vessels into small, medium and large vessel diseases. Currently, medical imaging has a pivotal role in the diagnosis of vasculitis given recent developments in the imaging of blood vessels. For example, early diagnosis of coronary artery aneurysms, a serious complication of Kawasaki disease, is now possible by magnetic resonance imaging (MRI) of the heart and multidetector computed tomography (MDCT); positron emission tomography/CT (PET/CT) helps to assess active vascular inflammation in Takayasu arteritis. Our review offers a unique approach using the integration of the proposed classification criteria for common systemic childhood vasculitides with their most frequent imaging findings, along with differential diagnoses and an algorithm for diagnosis based on common findings. It should help radiologists and clinicians reach an early diagnosis, therefore facilitating the ultimate goal of proper management of affected children.

¹8F-fluorodeoxyglucose positron emission tomography combined with whole-body computed tomographic angiography in critically ill patients with suspected severe sepsis with no definite diagnosis.

PURPOSE: Timely identification of septic foci is critical in patients with severe sepsis or septic shock of unknown origin. This prospective pilot study aimed to assess (18)F-fluorodeoxyglucose positron emission tomography (FDG-PET), combined with whole-body computed tomographic angiography (CTA), in patients with suspected severe sepsis and for whom the prior diagnostic workup had been inconclusive. METHODS: Patients hospitalized in an intensive care unit with a suspected severe sepsis but no definite diagnosis after 48 h of extensive investigations were prospectively included and referred for a whole body FDG-PET/CTA. Results from FDG-PET/CTA were assessed according to the final diagnosis obtained after follow-up and additional diagnostic workup. RESULTS: Seventeen patients were prospectively included, all on mechanical ventilation and 14 under vasopressor drugs. The FDG-PET/CTA exam 1) was responsible for only one desaturation and one hypotension, both quickly reversible under treatment; 2) led to suspect 16 infectious sites among which 13 (81 %) could be confirmed by further diagnostic procedures; and 3) triggered beneficial changes in the medical management of 12 of the 17 study patients (71 %). The FDG-PET/CTA images showed a single or predominant infectious focus in two cases where CTA was negative and in three cases where CTA exhibited multiple possible foci. CONCLUSION: Whole-body FDG-PET/CTA appears to be feasible, relatively safe, and provides reliable and useful information, when prospectively planned in patients with suspected severe sepsis and for whom prior diagnostic workup had been inconclusive. The FDG-PET images are particularly helpful when CTA exhibits no or multiple possible sites.

Safety of ventilation/perfusion single photon emission computed tomography for pulmonary embolism diagnosis.

PURPOSE: The aim of this management outcome study was to assess the safety of ventilation/perfusion single photon emission computed tomography (V/Q SPECT) for the diagnosis of pulmonary embolism (PE) using for interpretation the criteria proposed in the European Association of Nuclear Medicine (EANM) guidelines for V/Q scintigraphy. METHODS: A total of 393 patients with clinically suspected PE referred to the Nuclear Medicine Department of Brest University Hospital from April 2011 to March 2013, with either a high clinical probability or a low or intermediate clinical probability but positive D-dimer, were retrospectively analysed. V/Q SPECT were interpreted by the attending nuclear medicine physician using a diagnostic cut-off of one segmental or two subsegmental mismatches. The final diagnostic conclusion was established by the physician responsible for patient care, based on clinical symptoms, laboratory test, V/Q SPECT and other imaging procedures performed. Patients in whom PE was deemed absent were not treated with anticoagulants and were followed up for 3 months. RESULTS: Of the 393 patients, the prevalence of PE was 28 %. V/Q SPECT was positive for PE in 110 patients (28 %) and negative in 283 patients (72 %). Of the 110 patients with a positive V/Q SPECT, 78 (71 %) had at least one additional imaging test (computed tomography pulmonary angiography or ultrasound) and the diagnosis of PE was eventually excluded in one patient. Of the 283 patients with a negative V/Q SPECT, 74 (26 %) patients had another test. The diagnosis of PE was finally retained in one patient and excluded in 282 patients. The 3-month thromboembolic risk in the patients not treated with anticoagulants was 1/262: 0.38 % (95 % confidence interval 0.07-2.13). CONCLUSION: A diagnostic management including V/Q SPECT interpreted with a diagnostic cut-off of "one segmental or two subsegmental mismatches" appears safe to exclude PE.

Noninvasive cardiovascular imaging.

Over the past 2 decades, use of noninvasive cardiovascular imaging has increased dramatically. This article provides a brief synopsis of the current state of several technologies-- echocardiography, cardiac magnetic resonance imaging, and cardiac computed tomography--as well as a glimpse at future possibilities in cardiac imaging.

Early repolarization pattern associated with sudden cardiac death: long-term follow-up in patients with chronic heart failure.

BACKGROUND: Identification of patients with chronic heart failure (CHF) at a risk for sudden cardiac death (SCD) is an important objective. Early repolarization pattern (ERP) is associated with ventricular fibrillation in patients without structural heart diseases. Moreover, ERP was reported to be associated with SCD in patients with old myocardial infarction in a case-control study. However, little information is available on the prognostic significance of ERP in CHF patients. Thus, we aimed to investigate whether ERP is associated with SCD in CHF patients. METHODS AND RESULTS: The study population consisted of 132 consecutive outpatients with NYHA class I, II and III congestive heart failure and radionuclide left ventricular ejection fraction less than 40%. All patients underwent the standard 12-lead electrocardiogram at enrollment, where we assessed the presence of ERP using the criteria of J-point elevation ≥ 0.1 mV in at least 2 inferior or lateral leads. The primary endpoint of this study was SCD. At enrollment, 16 patients had ERP. During the follow-up period of 6.7 ± 3.5 years, 26 patients had SCD. Kaplan-Meier analysis showed that SCD was observed significantly more frequently in patients with ERP than in those without ERP (63% [10/16] vs 14% [16/116], P < 0.0001]. A multivariate Cox analysis revealed that ERP was significantly and independently associated with SCD (hazard ratio, 3.7; 95% confidence interval, 1.6-8.6; P = 0.002). CONCLUSION: ERP in inferior leads would be associated with an increased risk of SCD in CHF patients.