Cardio-toxicity among patients with sarcoma: a cardio-oncology registry.

BACKGROUND: Chemotherapy induced cardio-toxicity has been recognized as a serious side effect since the first introduction to anthracyclines (ANT). Cardio-toxicity among patients with breast cancer is well studied but the impact on patients with sarcoma is limited, even though they are exposed to higher ANT doses. The commonly used term for cardio-toxicity is cancer therapeutics related cardiac dysfunction (CTRCD), defined as a left ventricular ejection fraction (LVEF) reduction of > 10%, to a value below 53%. The aim of our study was to estimate the prevalence of CTRCD in patients diagnosed with sarcoma and to describe the baseline risk factors and echocardiography parameters among that population. METHODS: Data were collected as part of the Israel Cardio-Oncology Registry (ICOR), enrolling all patients evaluated in the cardio-oncology clinic at our institution. The registry was approved by the local ethics committee and is registered in clinicaltrials.gov (Identifier: NCT02818517). All sarcoma patients were enrolled and divided into two groups - CTRCD group vs. non-CTRCD group. RESULTS: Among 43 consecutive patients, 6 (14%) developed CTRCD. Baseline cardiac risk factors were more frequent among the non-CTRCD group. Elevated left ventricular end systolic diameter and reduced Global Longitudinal Strain were observed among the CTRCD group. During follow-up, 2 (33%) patients died in the CTRCD group vs. 3 (8.1%) patients in the non-CTRCD group. CONCLUSIONS: CTRCD is an important concern among patients with sarcoma, regardless of baseline risk factors. Echocardiography parameters may provide an early diagnosis of cardio-toxicity.

Diastolic strain time as predictor for systolic dysfunction among patients with active breast cancer.

BACKGROUND: Although diastolic dysfunction is common among patients treated with cancer therapy, no clear evidence has been shown that it predicts systolic dysfunction. This study evaluated the correlation of diastolic strain time (Dst) with the routine echocardiography diastolic parameters and estimated its role in the early detection of cardiotoxicity among patients with active breast cancer. METHODS: Data were collected as part of the Israel Cardio-Oncology Registry (ICOR), a prospective registry enrolling all adult patients referred to the cardio-oncology clinic. All patients with breast cancer, planned for Doxorubicin therapy, were included. Echocardiography, including global longitudinal systolic strain (GLS) and Dst, was assessed at baseline before chemotherapy (T1), during Doxorubicin therapy (T2) and after the completion of Doxorubicin therapy (T3). Cardiotoxicity was determined by GLS relative reduction of ≥15%. Dst was assessed as the time measured (ms) of the myocardium lengthening during diastole. RESULTS: Among 69 patients, 67 (97.1%) were females with a mean age of 52 ± 13 years. Dst was significantly associated with the routine diastolic parameters. Significant GLS reduction was observed in 10 (20%) patients at T3. Both in a univariate and a multivariate analyses, the change in Ds basal time from T1 to T2 emerged to be significantly associated with GLS reduction at T3 (P < .04). CONCLUSIONS: Among breast cancer patients, Dst showed high correlation to the routine diastolic echocardiography parameters. Change in Ds basal time emerged associated with clinically significant systolic dysfunction as measured by GLS reduction.

Cancer Therapeutics-Related Cardiac Dysfunction among Patients with Active Breast Cancer: A Cardio-Oncology Registry.

BACKGROUND: Progress in the treatment of breast cancer has led to substantial improvement in survival, but at the cost of increased side effects, with cardiotoxicity being the most significant one. The commonly used definition is cancer therapeutics-related cardiac dysfunction (CTRCD), defined as a left ventricular ejection fraction reduction of > 10%, to a value below 53%. Recent studies have implied that the incidence of CTRCD among patients with breast cancer is decreasing due to lower doses of anthracyclines and low association to trastuzumab and pertuzumab treatment. OBJECTIVES: To evaluate the prevalence of CTRCD among patients with active breast cancer and to identify significant associates for its development. METHODS: Data were collected as part of the Israel Cardio-Oncology Registry, which enrolls all patients who are evaluated at the cardio-oncology clinic at our institution. Patients were divided to two groups: CTRCD and no-CTRCD. RESULTS: Among 103 consecutive patients, five (5%) developed CTRCD. There were no significant differences in the baseline cardiac risk factors between the groups. Significant correlations of CTRCD included treatment with trastuzumab (P = 0.001) or pertuzumab (P < 0.001), lower baseline global longitudinal strain (GLS) (P = 0.016), increased left ventricular end systolic diameter (P < 0.001), and lower e' septal (P < 0.001). CONCLUSIONS: CTRCD is an important concern among patients with active breast cancer, regardless of baseline risk factors, and is associated with trastuzumab and pertuzumab treatment. Early GLS evaluation may contribute to risk stratification and allow deployment of cardioprotective treatment.

Circadian rhythm disruption in a mouse model of Rett syndrome circadian disruption in RTT.

Disturbances in the sleep/wake cycle are prevalent in patients with Rett syndrome (RTT). We sought to determine whether the circadian system is disrupted in a RTT model, Mecp2(-/y) mice. We found that MeCP2 mutants showed decreased strength and precision of daily rhythms of activity coupled with extremely fragmented sleep. The central circadian clock (suprachiasmatic nucleus) exhibited significant reduction in the number of neurons expressing vasoactive intestinal peptide (VIP) as well as compromised spontaneous neural activity. The molecular clockwork was disrupted both centrally in the SCN and in peripheral organs, indicating a general disorganization of the circadian system. Disruption of the molecular clockwork was observed in fibroblasts of RTT patients. Finally, MeCP2 mutant mice were vulnerable to circadian disruption as chronic jet lag accelerated mortality. Our finds suggest an integral role of MeCP2 in the circadian timing system and provides a possible mechanistic explanation for the sleep/wake distrubances observed in RTT patients. The work raises the possibility that RTT patients may benefit from a temporally structured environment.

Migrated Inferior Vena Cava (IVC) Filter Presenting as Tricuspid Valve Mass, Right-Sided Heart Failure, and Parodoxical Emboli.

A 58-year-old male with an unknown medical history presented with acute encephalopathy, receptive aphasia, and hypertensive emergency. The patient did not have any family members from whom a collateral history could be obtained. He underwent X-rays of the abdomen and bilateral humeri/femurs to check for foreign bodies. He was found to have right femoral open reduction and internal fixation with retained screw fragments. He was diagnosed with ischemic stroke on MRI. Transthoracic echocardiogram (TTE) revealed right-sided heart failure and a tricuspid valve mass as well as right to left shunting. This raised concern for large atrial septal defect (ASD) with paradoxical embolization from tricuspid valve mass. Transesophageal echocardiogram (TEE) redemonstrated large ASD. Concern was raised for the ASD closure device as the cause of this "tricuspid mass." Due to history of orthopedic procedure, it was hypothesized that the patient had an IVC filter placed in the setting of pulmonary embolism (PE) prior to an orthopedic procedure. The tricuspid valve was visualized under fluoroscopy and was confirmed to be a migrated IVC filter. He was taken to the operating room (OR) for cardiac surgery for the removal of the IVC filter and repair of ASD. Surprisingly, no ASD was found.

Unilateral renal artery stenosis causing hypertensive flash pulmonary oedema.

Flash pulmonary oedema can occur as a result of multiple triggers that may act independently or in concert. One such precipitating factor is bilateral renal artery stenosis which can be treated either with revascularisation or with medical therapy. Unilateral renal artery stenosis, however, is a rare cause of flash pulmonary oedema, especially when the contralateral kidney is still functional. We describe a case of an elderly woman with a history of heart failure with preserved ejection fraction and multiple hospitalisations for hypertensive crisis and flash pulmonary oedema who was found to have right, ostial renal artery stenosis that was treated with stent placement.

The association of reduced global longitudinal strain with cancer therapy-related cardiac dysfunction among patients receiving cancer therapy.

BACKGROUND: Cardiotoxicity is a leading cause of morbidity and mortality among patients receiving cancer therapy. The most commonly used definition is cancer therapy-related cardiac dysfunction (CTRCD) defined by a left ventricular ejection fraction reduction. Global longitudinal strain (GLS) has been implied to be superior in detecting early subclinical dysfunction. OBJECTIVES: Evaluate the prevalence of reduced GLS and whether it is associated with CTRCD development among patients receiving cancer therapy. METHODS: Data were collected as part of the Israel Cardio-Oncology Registry (ICOR), a prospective registry enrolling all adult patients receiving different types of cancer therapy, who were referred to the cardio-oncology clinic. Patients were divided into two groups-reduced GLS (> - 17%) vs. preserved GLS (≤ - 17%). Multivariable analyses were adjusted for a propensity score for baseline characteristics. RESULTS: Among 291 consecutive patients, 48 (16%) patients were included in the reduced GLS group. Overall, 11 (5%) patients developed CTRCD at following echocardiogram evaluation. Patients with preserved GLS had a significantly lower risk for CTRCD development [odds ratio (OR) 0.11, 95% confidence interval (CI) 0.03-0.41, p = 0.001], with every 1-unit improvement of GLS the risk of CTRCD decreased by 16% (OR 0.84, 95%CI 0.73-0.95, p = 0.007). After adjustment for baseline characteristics, including cardiovascular risk factors and systolic function, preserved GLS remained significantly associated with a lower risk for CTRCD development (OR 0.11, 95%CI 0.02-0.64, p = 0.014), with every 1-unit improvement lowering the risk by 19% (OR 0.81, 95%CI 0.67-0.98, p = 0.032). CONCLUSIONS: Reduced GLS is common among patients receiving cancer therapy and may identify patients at increased risk for CTRCD development.

Usefulness of Global Longitudinal Strain for Early Identification of Subclinical Left Ventricular Dysfunction in Patients With Active Cancer.

Cardiotoxicity from cancer therapy has become a leading cause of morbidity and mortality in cancer survivors. The most commonly used definition is cancer therapeutic related cardiac dysfunction defined as a left ventricular ejection fraction (LVEF) reduction of >10%, to a value below 50%. However, according to the recent American and European Society of Echocardiography, global longitudinal strain (GLS) is the optimal parameter for early detection of subclinical left ventricular dysfunction. The objective of this study was to evaluate the frequency of GLS reduction in patients with active cancer and its correlation to other echocardiographic parameters. Data were collected as part of the International Cardio-Oncology Registry. All patients performed at least 2 echocardiograms including GLS. We evaluated the frequency of GLS reduction (≥10% relative reduction), its correlation to LVEF reduction and whether there are other predicting echocardiographic parameters. In 64 consecutive patients, 12 (19%) had ≥10% GLS relative reduction, of which 75% had no concomitant ejection fraction reduction. There were no significant differences in the baseline cardiac risk factors (hypertension, diabetes, hyperlipidemia, or smoking). Treatment with Doxorubicin, Pertuzumab, or Ifosfamide was significantly more frequent in patients GLS reduction. No other echocardiographic parameters, including diastolic function or systolic pulmonary artery pressure were significant predictors for GLS reduction. In conclusion, our study demonstrates that GLS reduction is frequent in active cancer patients, precedes LVEF reduction and cannot be anticipated by other echocardiographic parameters. Using GLS routinely during therapy may lead to an early diagnosis of cardiotoxicity.