Occurrence Of Cardiac Toxicity Research Articles

Preventive Effects of Cardotoxicities By Liposomal Anthracyclines non Pegilated in 95 Perspective Patients Affected By Lymphoma and Monitored By Biomarkers and Ecocardiography

Anthracyclines (AC) still constitute the mainstay of the 1st line treatment in lymphoma: their use, however, is limited by the occurrence of Cardiac Toxicity (CT). The exact prevalence of AC CT occurring after widely used regimens such as R-CHOP or ABVD is unknown and there is uncertainty about the best monitoring method and possible prophylactic or therapeutic interventions. METHODSWe started a prospective observational trial in lymphoma patients undergoing treatment with conventional or liposomal AC. We used a comprehensive approach to monitor for AC CT, using a telemedicine(TM) system integrating echocardiography, ECG and biomarkers (Troponin I - TnI). RESULTSIn this final analysis, 95 patients completed the planned treatment (52 males and 43 females). Median age was 56.03 years (range 19.1 to 78.5 years), and 36 patients were > 65 years. 23 were HL and 72 NHL (DLBCL was the most represented subtype with 47 cases). Liposomal AC was used in 31 patients and classical AC in 64, with mean cumulative doses of 283.33 and 272.76 mg/sqm, respectively.10/95 patients (11%) developed a TnI rise above 0.08 ng/ml and 39/95 (41%) above 0.03 ng/ml. With both cut-offs, the rises occurred more frequently at cumulative doses >200 mg/sqm. The major arising occurred in the group underwent classical AC, while in the group underwent liposomal AC although the value before first infusion was in 10% more than 0.03 at the cumulative dose of 300 mg /sqm there’s a plateau of troponin value.Thanks to this monitoring system we noticed 2 Acute cardiac toxicity events with resolution in 100% of cases. Furthermore in those cases where has registered a subclinical CT has begun a prompt Cardiological therapy by ACE inhibitors and Beta Blocker to reduce the relative risk of Cardiological events. CONCLUSIONSEven with low cumulative doses, with a median follow up of 13 months, subclinical signs of AC CT were found in at least 11% of patients. The use of liposomal AC allow the safe treatment of patients with a previous heart disease diagnosis rather it seem protective in the higher cumulative doses.A longer follow up will be able to clarify the impact of arising of TnI more than 0.03 and 0.08 on the developing of AC CT in all our series.On the basis of our experience a multicentric trial has begun on behalf Italian Lymphoma Foundation (FIL)In a low-risk setting for AC CT, a monitoring strategy combining clinical, imaging, instrumental and biomarker data seems to enhance the sensitivity of separate methods. This strategy is feasible and resource-saving thanks to the integration in a TM system. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Electrocardiographic Findings in Patients with Acute Methadone Poisoning

Background : Methadone as a synthetic opioid is widely used for treatment of opioid dependency. One of the causes of methadone related sudden death is cardiac toxicity. This study was aimed to determine the electrocardiographic changes in acute methadone poisoning. Methods: This is a cross sectional study on patients older than 12 years old with acute methadone poisoning who were admitted in Loghman poisoning center at 2010-2011. Data analysis was done by means of SPSS version 16 and appropriate statistical tests at the significant level of P<0.05. Results: In one year period, 51 patients with mean age of 40.59±18.27 (31-51) years, including 39 males, with acute methadone poisoning were included in to the study. Seven patients (13.7%) were acutely poisoned, 29 patients (56.8%) had acute on chronic methadone poisoning and others had not reliable history. The mean time of PR, QRS and QTc were 150.2±34.22, 77.06±13.89 and 421.76±43.04ms, respectively. The prolongation of PR, QRS and QTc were observed in 9.8%, 1.96% and 17.6% of patients, respectively. A significant statistical association was observed between PR prolongation and type of poisoning and QRS prolongation and outcome (P=0.035 and 0.009). Conclusion: The findings of this study indicate the occurrence of cardiac toxicity in patients with acute methadone poisoning. Further studies are required on acute methadone poisoning in patients with known previous cardiac status.

Model-Based Evaluation and Optimization of Cardiac Monitoring Protocols for Adjuvant Treatment of Breast Cancer with Trastuzumab

Trastuzumab treatment is associated with occurrence of cardiac toxicity, for which monitoring of the left ventricular ejection fraction (LVEF) is indicated. The performance of the currently used monitoring protocol as defined in the summary of product characteristics (SPC) is however unknown. The objective of this analysis was to develop a model-based framework for evaluation and optimization of cardiac monitoring strategies. The model-based framework comprised a previously developed exposure-response model for trastuzumab induced changes in LVEF, and a protocol-execution model that allowed incorporation of treatment interventions as described by a monitoring protocol. Metrics for evaluation of toxicity, dose intensity and monitoring burden were defined to allow evaluation and optimization of cardiac monitoring protocols. The success of a protocol-defined dose reduction was improved from 40% for the SPC-based protocol, to 79% for a scoring-based protocol, thereby decreasing the observed severity of cardiotoxicity. Including adaptation based on risk-profile allowed reduction of the mean number of LVEF measurements by 19%. This model-based evaluation approach enabled evaluation and optimization of cardiac monitoring protocols that would be difficult to evaluate in a clinical setting. This approach can potentially be applied for other drugs that use repeated evaluation of continuous biomarkers for toxicity.

Lipid Emulsion as Rescue Therapy in Lamotrigine Overdose

Background Lamotrigine is a sodium channel blocking agent that is widely prescribed for treatment of seizure. Although life-threatening effects are rarely observed in overdose, some previous reports have described the occurrence of cardiac toxicity. The management of sodium channel blocking agent-induced cardiotoxicity conventionally requires sodium bicarbonate administration. Recent case reports describe intravenous lipid administration as a successful treatment for refractory cardiovascular collapse induced by sodium channel blocking medications. Objective The objective of this study is to report the use of intravenous lipid emulsion as adjunctive therapy in a case of lamotrigine overdose in which electrocardiographic changes were unresponsive to bicarbonate therapy. Case Report We report a case of intentional lamotrigine overdose in a 50-year-old woman who lost consciousness and developed electrocardiographic aberrations, including widening of QRS with occurrence of left bundle branch block. The patient was initially treated with sodium bicarbonate without effect. Recovery of cardiac conduction was rapidly achieved after infusion of a 20% lipid emulsion. The exact mechanism of action of lipid emulsion is not fully understood. The lipophilic properties of lamotrigine suggest that it was partially removed by the plasmatic lipid emulsion. Conclusion This case provides additional insight into the potential benefit of using lipid emulsion in refractory sodium channel blocking intoxications.

Intraoperative chemotherapy with cisplatin and epinephrine after cytoreductive surgery in patients with recurrent ovarian cancer: a phase I study

Intraperitoneal (i.p.) epinephrine was shown to increase the accumulation of i.p. cisplatin in tumours, and thus its antitumour effect in a model of peritoneal carcinomatosis in rats. To determine the tolerance to i.p. epinephrine with cisplatin, 18 patients with recurrent ovarian carcinoma were intraoperatively treated in this phase 1 study. After maximal cytoreductive surgery, the peritoneal cavity was filled twice for 1 h with 30 mg/l of cisplatin and increasing concentrations of epinephrine (0, 1, 2, 3 mg/l) in 3 l of saline solution at 37 degrees C. No deaths occurred. Three patients were treated at each of the 0, 1 and 2 mg/l epinephrine levels without adverse events. Two of the three patients who received 3 mg/l epinephrine experienced cardiac intolerance. Six additional patients received 2 mg/l of epinephrine without toxicity. A relationship between the serum concentration of epinephrine and occurrence of cardiac toxicity was established. A 60% decrease in serum area under the curve of platinum was calculated in patients receiving i.p. epinephrine compared with i.p. cisplatin alone. Renal toxicity from cisplatin was not increased by epinephrine. No haematological or neurological toxicity was recorded. The other grade 3-4 adverse events [thromboembolism (5), peritonitis (1), abdominal bleeding (1), bowel fistula (1)] occurred as often as usually reported for this heavy surgical procedure. The combination of i.p. epinephrine with cisplatin as intraoperative chemotherapy after optimal cytoreductive surgery is feasible. The recommended concentration for further studies is 2 mg/l for i.p. epinephrine.

Tolerability in patients receiving trastuzumab with or without chemotherapy

One of the major expectations from the use of humanized monoclonal antibodies in cancer therapy has been that of exploiting the specificity and sensitivity of the immune system to achieve selective therapeutic effects devoid of the often severe toxicity caused by chemotherapy. The tolerability of trastuzumab (Herceptin) as it emerged from the trials where the drug was used as a single agent or in combination with chemotherapy largely confirmed that expectation. Adverse events most frequently encountered include mild-to-moderate, transient effects related to administration of the first dose of trastuzumab. The incidence of severe or serious adverse effects attributable to trastuzumab was low. However, the occurrence of cardiac toxicity that was unexpectedly high, especially in patients previously or concomitantly treated with anthracyclines, could not be predicted on the basis of the putative mechanism of action of the antibody. The safety profile of trastuzumab is discussed here with a particular focus on cardiotoxicity and the issues relating to patient management during trastuzumab therapy.

Dihydropyrimidine dehydrogenase deficiency and fluorouracil-related toxicity.

Dihydropyrimidine dehydrogenase (DPD) is the initial and rate-limiting enzyme of 5-fluorouracil (5-FU) catabolism. We report lymphocytic DPD data concerning a group of 53 patients (23 men, 30 women, mean age 58, range 36–73), treated by 5-FU-based chemotherapy in different French institutions and who developed unanticipated 5-FU-related toxicity. Lymphocyte samples (standard collection procedure) were sent to us for DPD determination (biochemical method). Among the whole group of 53 patients, 19 had a significant DPD deficiency (DD; below 150 fmol min−1 mg−1 protein, i.e. less than 70% of the mean value observed from previous population study). There was a greater majority of women in the DD group (15 out of 19, 79%) compared with the remaining 34 patients (15 out of 34, 44%, P<0.014). Toxicity was often severe, leading to patient death in two cases (both women). The toxicity score (sum of WHO grading, theoritical range 0–20) was twice as high in patients with marked DD (below 100 pmol min−1 mg−1 protein, n = 11, mean score = 13.2) compared with patients with moderate DD (between 150 and 100 pmol min−1 mg−1 protein, n = 8, mean score = 6.8), P = 0.008. In the DD group, there was a high frequency of neurotoxic syndromes (7 out of 19, 37%). The two deceased patients both had severe neurotoxicity. The occurrence of cardiac toxicity was relatively rare (1 out of 19, 5%). These data suggest that women are particularly prone to DPD deficiency and allow a more precise definition of the DD toxicity profile. © 1999 Cancer Research Campaign

Cardiac toxicity of bone marrow transplantation: predictive value of cardiologic evaluation before transplant.

This study analyses the risk of cardiac complications and its individual predictability in bone marrow transplantation (BMT). One hundred seventy patients undergoing allogeneic (n = 150) or autologous (n = 20) BMT were evaluated by physical examination, history, rest and exercise ECG, chest x-ray, two-dimensional echocardiography, and radionuclide ventriculography (RNV) before BMT, and monitored for 3 months thereafter. Following BMT, cardiac toxicity occurred in eight patients (4.7%). Three patients (1.8%) developed life-threatening toxicity (pericardial effusion and left ventricular failure, n = 2; sudden cardiac arrest, n = 1). Thirty-eight patients (22%) had pathologic findings before BMT. In 22 patients, left ventricular ejection fraction (EF) determined by RNV was reduced to less than 55%. This was the only abnormality in 17 patients and was generally mild, with a lowest EF of 42%. There was no correlation between overall results of cardiologic evaluation before BMT and cardiac toxicity. Cardiotoxic events occurred more frequently in patients with a reduced EF (P < .05). However, this was restricted to minor cardiac events. Life-threatening cardiac toxicity was not significantly increased in patients with pathologic results before BMT. Moreover, none of the patients with an EF less than 50% developed cardiac toxicity. Life-threatening cardiac toxicity is rare after BMT, occurring in less than 2% of all patients. Although the occurrence of cardiac toxicity is correlated with a reduction of EF before BMT, life-threatening cardiac toxicity cannot be predicted in individual patients.