ECG Scoring for the Evaluation of Therapy-Naïve Cancer Patients to Predict Cardiotoxicity.

OBJECTIVE: To evaluate a new electrocardiographic (ECG) score reflecting domains of electrical and structural alterations in therapy-naïve cancer patients to assess their risk of cardiotoxicity. METHODS: We performed a retrospective analysis of 134 therapy-naïve consecutive cancer patients in our two university hospitals concerning four ECG score parameters: Contiguous Q-waves, markers of left ventricular (LV) hypertrophy, QRS duration and JTc prolongation. Cardiotoxicity was assessed after a short-term follow-up (up to 12 months). RESULTS: Of all the patients (n = 25), 19% reached 0 points, 50% (n = 67) reached 1 point, 25% (n = 33) reached 2 points, 5% (n = 7) reached 3 points and 0.7% reached 4 or 5 points (n = 1 respectively). The incidence of cardiotoxicity (n = 28 [21%]) increased with the ECG score, with 0 points at 0%, 1 point 7.5%, 2 points 55%, 3 points 71% and ≥3 points 50%. In the ROC (Receiver operating curves) analysis, the best cut-off for predicting cardiotoxicity was an ECG score of ≥2 points (sensitivity 82%, specificity 82%, AUC 0.84, 95% CI 0.77-0.92, p < 0.0001) which was then defined as a high-risk score. High-risk patients did not differ concerning their age, LV ejection fraction, classical cardiovascular risk factors or cardiac biomarkers compared to those with a low-risk ECG score. CONCLUSION: ECG scoring prior to the start of anti-cancer therapies may help to identify therapy-naïve cancer patients at a higher risk for the development of cardiotoxicity.

Assessment of coronary artery disease during hospitalization for cancer treatment.

BACKGROUND: With improvement of cancer-specific survival, comorbidities and treatment-related side effects, particularly cardiovascular toxicities, need close attention. The aim of the present study was to evaluate clinical characteristics and outcomes of cancer patients requiring coronary angiography during inpatient care. METHODS: We performed a retrospective analysis of patients hospitalized between 02/2011 and 02/2018 in our two university hospital cancer centers. From a cohort of 60,676 cancer patients, we identified 153 patients (65.7 ± 11.6 years, 73.2% male), who underwent coronary angiography and were eligible for analysis. These were compared to a control group of 153 non-cancer patients pair-matched with respect to age, sex, and indication for catheterization. RESULTS: Cancer patients presented in 66% with an acute coronary syndrome (ACS). The most prevalent cancer entities were lymphoma (19%) and lung cancer (18.3%). The rate of primary percutaneous coronary interventions (PCI) was significantly lower in the cancer cohort (40.5% vs. 53.6%, p = 0.029), although manifestation of coronary artery disease (CAD) and PCI results were comparable (SYNergy between PCI with TAXus and cardiac surgery (SYNTAX)-score, delta pre- and post-PCI - 9.8 vs. - 8.0, p = 0.2). Mortality was remarkably high in cancer patients (1-year mortality 46% vs. 8% in non-cancer patients, p < 0.001), particularly with troponin-positive ACS (5-year mortality 71%). CONCLUSION: Strategies to effectively control cardiovascular risks in cancer patients are needed. Additionally, suspected CAD in cancer patients should not prevent prompt diagnostic clarification and optimal revascularization as PCI results in cancer patients are comparable to non-cancer patients and occurrence of troponin-positive ACS leads to a significantly increased risk of mortality.

Cardiovascular Damage Associated With Chest Irradiation.

The improvement of anticancer-therapies results in a greater amount of long-term survivors after radiotherapy. Therefore, the understanding of cardiotoxicity after irradiation is of increasing importance. Cardiovascular adverse events after chest irradiation have been acknowledged for a long time but remain difficult to diagnose. Long-term cardiovascular adverse events may become evident years or decades after radiotherapy and the spectrum of potential cardiovascular side effects is large. Recent experimental and clinical data indicate that cardiovascular symptoms may be caused especially by heart failure with preserved ejection fraction, which remains incompletely understood in patients after radiation therapy. Heart radiation dose and co-existing cardiovascular risk factors represent some of the most important contributors for incidence and severity of radiation-induced cardiovascular side effects. In this review, we aim to elucidate the underlying patho-mechanisms and to characterize the development of radiation-induced cardiovascular damage. Additionally, approaches for clinical management and treatment options are presented.

Cardiac biomarkers for the detection of cardiotoxicity in childhood cancer-a meta-analysis.

AIMS: Childhood cancer therapy is associated with a significant risk of therapy-related cardiotoxicity. This meta-analysis aims to evaluate cardiac biomarkers for the detection of cancer therapy-related left ventricular (LV) dysfunction in childhood cancer patients. METHODS AND RESULTS: PubMed, Cochrane Library, Wiley Library, and Web of Science were screened for studies investigating brain natriuretic peptide (BNP)/N-terminal proBNP (NT-proBNP) or cardiac troponin in childhood cancer patients. The odds ratios (OR) for elevation of cardiac biomarkers and association with LV dysfunction were calculated using a random-effects model. Data from 27 studies with 1651 subjects were included. BNP/NT-proBNP levels were higher post-treatment compared with controls or pre-treatment values [standardized mean difference = 1.0; 95% confidence interval (CI) = 0.6-1.4; n = 320; P < 0.001]. LV dysfunction was present in 11.76% of included patients, and risk for LV dysfunction was increased in patients with elevated BNP/NT-proBNP (OR = 7.1; 95% CI = 2.0-25.5; n = 350; P = 0.003). The sensitivity of BNP/NT-proBNP for the detection of LV dysfunction was 33.3%, and the specificity was 91.5%. Sensitivity increased when selecting for studies that assessed patients < 5 years after anthracycline exposure and for studies including high cumulative anthracycline doses. Anthracycline chemotherapy was associated with an increased frequency of elevated troponin (OR = 3.7; 95% CI = 2.1-6.5; n = 348; P < 0.001). The available evidence on the association between elevated troponin and LV dysfunction was insufficient for an adequate analysis. In five included studies, the frequency of LV dysfunction was not increased in patients with elevated troponin (OR = 2.5; 95% CI = 0.5-13.2; n = 179; P = 0.53). CONCLUSIONS: BNP/NT-proBNP is associated with cardiotoxicity in paediatric cancer patients receiving anthracycline therapy, but owing to low sensitivity, BNP/NT-proBNP has to be evaluated in the context of further parameters including clinical assessment and echocardiography. Future studies are needed to determine whether troponin serves as a marker for cardiotoxicity in children. Standardized recommendations for the application of cardiac biomarkers in children undergoing cardiotoxic cancer therapy may benefit management and clinical outcome.

Impact of Cancer in Patients Undergoing Transcatheter Aortic Valve Replacement: A Single-Center Study.

BACKGROUND: The use of transcatheter aortic valve replacement (TAVR) in cancer survivors and patients with active cancer (AC) in cancer survivors and patients with active cancer (AC) is expanding, suggesting a need to adjust the indications and risk assessment pre-TAVR. OBJECTIVES: The purpose of this study was to determine the impact of cancer on peri-procedural complications and survival in a long-term, single-center cohort of patients treated with TAVR. METHODS: Patients treated with TAVR between January 2006 and December 2018 were grouped as follows: controls (patients without cancer), stable cancer (SC), and AC. The primary endpoints were peri-procedural complications and 30-day survival. A secondary endpoint was 10-year survival. RESULTS: A total of 1,088 patients (age 81 ± 5 years, 46.6% men) treated with transfemoral TAVR were selected: 839 controls, 196 SC, and 53 AC. Predominant malignancies were breast, gastrointestinal, and prostate cancer. No differences were observed between patients with cancer and controls regarding peri-procedural complications. Patients with AC had similar 30-day survival compared with controls and SC (94.3% vs. 93.3% vs. 96.9%, p = 0.161), but as expected, reduced 10-year survival. AC was associated with a 1.47 (95% CI 1.16 to 1.87) fold increased risk of all-cause 10-year mortality in multivariable adjusted models. CONCLUSIONS: TAVR should be performed in patients with cancer when indicated, considering that patients with cancer have similar periprocedural complications and short-term survival compared with control patients. However, patients with AC have worse 10-year survival. Future studies are needed to define cancer-specific determinants of worse long-term survival.

Cardiovascular Adverse Events Associated With BRAF and MEK Inhibitors: A Systematic Review and Meta-analysis.

Importance: Cardiovascular adverse events (CVAEs) after treatment with BRAF and MEK inhibitors in patients with melanoma remain incompletely characterized. Objective: To determine the association of BRAF and MEK inhibitor treatment with CVAEs in patients with melanoma compared with BRAF inhibitor monotherapy. Data Sources: PubMed, Cochrane, and Web of Science were systematically searched for keywords vemurafenib, dabrafenib, encorafenib, trametinib, binimetinib, and cobinimetinib from database inception through November 30, 2018. Study Selection: Randomized clinical trials reporting on CVAEs in patients with melanoma being treated with BRAF and MEK inhibitors compared with patients with melanoma being treated with BRAF inhibitor monotherapy were selected. Data Extraction and Synthesis: Data assessment followed the Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) guidelines. Pooled relative risks (RRs) and 95% CIs were determined using random-effects and fixed-effects analyses. Subgroup analyses were conducted to assess study-level characteristics associated with CVAEs. Main Outcomes and Measures: The selected end points were pulmonary embolism, a decrease in left ventricular ejection fraction, arterial hypertension, myocardial infarction, atrial fibrillation, and QTc interval prolongation. All-grade and high-grade (≥3) CVAEs were recorded. Results: Overall, 5 randomized clinical trials including 2317 patients with melanoma were selected. Treatment with BRAF and MEK inhibitors was associated with an increased risk of pulmonary embolism (RR, 4.36; 95% CI, 1.23-15.44; P = .02), a decrease in left ventricular ejection fraction (RR, 3.72; 95% CI, 1.74-7.94; P < .001), and arterial hypertension (RR, 1.49; 95% CI, 1.12-1.97; P = .005) compared with BRAF inhibitor monotherapy. The RRs for myocardial infarction, atrial fibrillation, and QTc prolongation were similar between the groups. These results were consistent when assessing high-grade CVAEs (left ventricular ejection fraction: RR, 2.79; 95% CI, 1.36-5.73; P = .005; I2 = 29%; high-grade arterial hypertension: RR, 1.54; 95% CI, 1.14-2.08; P = .005; I2 = 0%), but RRs for high-grade pulmonary embolism were similar between groups. A higher risk of a decrease in left ventricular ejection fraction was associated with patients with a mean age younger than 55 years (RR, 26.50; 95% CI, 3.58-196.10; P = .001), and the associated risk of pulmonary embolism was higher for patients with a mean follow-up time longer than 15 months (RR, 7.70; 95% CI, 1.40-42.12; P = .02). Conclusions and Relevance: Therapy with BRAF and MEK inhibitors was associated with a higher risk of CVAEs compared with BRAF inhibitor monotherapy. The findings may help to balance between beneficial melanoma treatment and cardiovascular morbidity and mortality.

Ticagrelor Leads to Statin-Induced Rhabdomyolysis: A Case Report.

BACKGROUND Following acute coronary intervention in cardiology patients, the combined medical therapy with the platelet inhibitory drug ticagrelor and a statin medication (e.g., simvastatin) is recommended according to international guidelines. Yet combined therapeutic regimens have the potential of pharmacological interaction with both ticagrelor and simvastatin being metabolized by CYP3A4. Rhabdomyolysis is a known side-effect of statin therapy and combined therapy increases the susceptibility to this complication. CASE REPORT A 72-year-old patient presented to our Emergency Department with typical signs of rhabdomyolysis consisting of muscular cramps and pain in both legs and a significant elevation of creatinine kinase (CK). Five months prior to this presentation, he had been hospitalized due to acute coronary syndrome followed by a coronary intervention of a high-grade left anterior descending artery stenosis. His long-term medication included simvastatin 20 mg daily, which he had taken for several years, and ticagrelor, which had been added to his medication following coronary intervention. The patient showed fast recovery of symptoms and rapid normalization of CK levels upon treatment change from ticagrelor to clopidogrel with a paused statin administration. CONCLUSIONS The combined use of ticagrelor with low dose simvastatin poses a risk for rhabdomyolysis even in patients with normal kidney function. Patients treated with ticagrelor might require changes in statin therapy and dose adjustments in order to avoid pharmacological interactions and higher risk for adverse effects.