Noëlle Vignat

Cardiac side-effects of cancer chemotherapy

The spectrum of cardiac side-effects of cancer chemotherapy has expanded with the development of combination, adjuvant and targeted chemotherapies. Their administration in multiple regimens has increased greatly, including in older patients and in patients with cardiovascular and/or coronary artery disease (CAD). Cardiac toxicity of anthracyclines involves oxidative stress and apoptosis. Early detection combines 2D-echocardiography and/or radionuclide angiography and recent methods such as tissue Doppler imaging, strain rate echocardiography and sampling of serial troponin and/or NT-proBNP levels. Dexrazoxane has proven effective in the prevention of dose-related toxicity in children and adults. High doses of the alkylating drugs cyclophosphamide and ifosfamide may result in a reversible heart failure and in life-threatening arrhythmias. Myocardial ischemia induced by the antimetabolites 5-fluorouracil and capecitabine impacts prognosis of patients with prior CAD. Severe arrhythmias may complicate administration of microtubule inhibitors. Targeted therapies with the antibody-based tyrosine kinases (TK) inhibitors trastuzumab and, to a lesser extent, alemtuzumab induce heart failure or asymptomatic LV dysfunction in 1-4% and 10%, respectively. Cetuximab and rituximab induce hypotension, whereas bevacizumab may promote severe hypertension and venous thromboembolism. Small molecule TK inhibitors may also elicit LV dysfunction, in only few patients treated with imatinib mesylate, but in a substantially higher proportion of those receiving the multitargeted TK inhibitor sunitinib or the recently approved drugs erlotinib, lapatinib and dasatinib. Management of patients at increased cardiovascular risk associated with advancing age, previous CAD or targeted therapies may be optimized by referral to a cardiologist in a cross-specialty teamwork.

HIV-associated vascular diseases: Structural and functional changes, clinical implications

After more than two decades of AIDS epidemic, the spectrum of HIV-associated vascular diseases has mainly evolved from infectious and inflammatory vasculitides to premature atherosclerosis, its related contributing conditions (metabolic syndrome, dyslipidemia, insulin resistance syndrome) and complications (acute coronary and cerebrovascular syndromes). Today, as the AIDS epidemic further progresses worldwide and as the life expectancy of HIV-infected patients treated with effective antiviral regimens has dramatically increased, more than 10% of patients experience cardiovascular manifestations. The complex interplay between viral infection, inflammatory and cytokines pathways, protease inhibitors-induced hyperlipidemia and direct effects on endothelial cells has not, by far, been integrated in a single comprehensive pathogenesis network. However, recognition of its main components has resulted in a broader appreciation of cardiovascular risk and risk factors in HIV-infected/treated patients. Cardiovascular prevention is required in more than one half of HIV-infected/treated patients to achieve a reliable effectiveness of modern antiretroviral therapy. As the prognosis of HIV patients improves continuously, this rate is also likely to increase in the future.

Cardiogenic shock associated with reversible dilated cardiomyopathy during therapy with regular doses of venlafaxine

We report a cardiac complication in a patient treated with regular doses of venlafaxine. A 49-year-old man with prior normal cardiac function and stable chronic hepatitis C was treated for a major depressive disorder with usual doses of venlafaxine during an 8-month period until the occurrence of a cardiogenic shock in a context of dilated cardiomyopathy. Three months after withdrawal of the drug, the left ventricular ejection fraction returned to normal values. Cardiomyopathy is a rare complication with high doses of venlafaxine that was not previously reported in patients free of prior cardiac disease and cardiomyopathy and treated with usual doses (initially 150 mg daily; after 3 months, 75 mg daily). An objective assessment revealed that venlafaxine was probably implied in the subsequent development of cardiomyopathy when considering the Naranjo Probability Scale. Physicians who usually prescribe venlafaxine have to be briefed on such potential cardiac adverse effects even with usual doses.

Oxidative Stress in Patients with Acute Heart Failure

Oxidative stress (OS) is a keystone in the pathology of the ischemia reperfusion sequence (acute coronary syndromes, cardiac surgery, transplantation). In heart failure, the implication of OS is less understood. This study was intended to evaluate OS in acute heart failure. Criteria for inclusion were consecutive patients hospitalized in our cardiology department for a first pulmonary edema that revealed a dilated cardiomyopathy (DCM). Exclusion criteria included known cardiomyopathy, smoker, acute coronary syndrome, and treatment with angiotensin converting enzyme inhibitors (ACEI) or angiotensin II receptor blockers (ARAII). OS was evaluated in blood samples: thiobarbituric acid-reactive substances (TBARS), total antioxidant status (TAS), plasma alpha-tocopherol, vitamin A, and beta-carotene. Standard biochemical parameters including CRP, fibrinogen, lipid, and creatinine were assayed. Ten patients (80% men, mean age 55.3 +/- 7.9 years) were included and followed during a 6 month period. The etiologies of DCM were alcohol (n = 3), anti-cancer drugs (n = 2), valvulopathies (n = 2), or idiopathic (n = 3). In acute heart failure, TBARS were elevated (1.69 micromol/L; normal value 0.6-4.2 micromol/L) and TAS status was decreased (0.96 mmol/L; normal value 1.3-1.9 pmol/L). OS was more important when patients had atrial or ventricular arrhythmia. Nevertheless, liposoluble antioxidant parameters (beta-carotene, vitamin A, alpha-tocopherol) had a usual value. At the term of the follow-up, patients returned to a stable condition, OS markers revealed normal values, and every Holter ECG showed no supraventricular or ventricular arrhythmias. In acute heart failure, oxygen-free radicals are increased. We thus hypothetized that a modification in OS could be responsible for arrhythmias and complications of acute heart failure.

Oxidative Stress Implication After Prolonged Storage Donor Heart with Blood Versus Crystalloid Cardioplegia and Reperfusion Versus Static Storage

Several factors are known to limit cardiac transplantation, such as number of donors, quality of cardiac graft preservation, and ischemia-reperfusion injury. Some mechanisms of reperfusion injury are now recognized; they include oxygen free radical (OFR), white blood cells activation, changes in calcium influx, alteration of microvascular blood flow, and sympathetic activation. The goal of this study was to assess the effects of two types of cardioplegia with long-term storage, either static or continuous perfusion, in 30 isolated sheep hearts as a model for heart transplantation. We examined myocardial function, histology, ischemic damage, and markers of oxidative stress. Two types of cardioplegia and storage conditions using a Langendorff reperfusion were studied in a combined approach: crystalloid (CP) [groups I and III] or cold oxygenated autologous blood (BC) [groups II and IV], immediate storage during 8h in profound hypothermia (groups I and II), or reperfused with crystalloid (group III), or blood cardioplegia (group IV). All perfusate samples were drawn from the coronary sinus. Lactate levels increased progressively in groups I, II, and IV, but not in group III, as no significant elevation was shown [90 min: 13.6+/-1.7 versus 5.2+/-1.0 mmol/L (P<0.01)]. Arrhythmias were more frequent when using BC (n=5) than CP (n=0). For plasma thiobarbituric acid-reactive substances (TBARS) levels a significant difference was found between group III and the other groups since 15 to 90 min (P<0.05). Vitamin E concentration decreased significantly from 5 min for groups II and IV, 15 min for group I, and 30 min for group III, with a significant difference between groups II and IV (P<0.05) but not between groups I and III. CP followed by a reperfusion with the same solution showed a significantly lower ischemic injury and OFR production, less frequent ventricular arrhythmias while stable hemodynamic parameters carried on. However, this protocol did not act on the early postoperative contractile function.

Persistent symptomatic pleural effusion following coronary bypass surgery: clinical and histologic features, and treatment

Pleural effusions following coronary artery bypass grafting (CABG) have been reported in 65%–89% of the cases. The majority of pleural effusions are left-sided, of little significance, and resolve spontaneously. However, a few pleural effusions require specific therapeutics. We report clinical and pleural histologic features of three patients who had persistent post-CABG pleural effusions and underwent video-assisted thoracic surgery (VATS). These patients were studied because they had a persistent pleural effusion within the first 2 months after CABG without other identifiable causes. All patients underwent VATS for investigation and management of persistent pleural effusions. Three patients with a mean age of 63.6 ± 8.5 years were studied. The pleural effusion developed 38 ± 11.3 days after CABG (range: 22–46). The median period from CABG to VATS was 80 ± 21.6 days (range: 50–100). In all cases, the pleural effusion was large, and predominated on the left side. Pleural effusions were characterized by an exudative (n = 2) or transudative (n = 1) fluid with lymphocytosis. Histologic examination of pleural biopsies showed a follicular lymphoid hyperplasia involving the pleural serosa and a non-necrotizing granulomatous reaction with a mild inflammatory infiltrate. All patients underwent VATS with intrapleural injection of sclerosing agents. Video-assisted thoracic surgery talc pleurodesis led to symptomatic and radiologic improvement in all patients with a mean follow-up of 16.7 ± 4.5 months. No recurrence of pleural effusion has been observed in any patient. Large pleural effusions can develop in a small proportion of patients after CABG. The mechanism of pleural effusion remains unclear. Video-assisted thoracic surgery could play a significant role in the management of pleural effusion developing after CABG.

087 Oxidative stress implication in cardiogenic shock with ischemic or idiopathic severe left ventricular dysfunction: role of etiologies of cardiomyopathies

Background Oxidative stress (OS) implication is paramount in pathology: ischemia reperfusion sequence (acute coronary syndrome, cardiac surgery, transplantation). Involvement of OS in heart failure (HF) is less known but is increased in the failing heart, and this might contribute to the pathogenesis of myocardial remodeling and HF. Aim Prospective study to identify OS in plasma from patients with a cardiogenic shock and to evaluate the role of etiologies of cardiomyopathy: ischemia or no. Methods Consecutive patients hospitalized in the cardiology unit with a first cardiogenic shock that complicated an idiopathic or ischemic dilated cardiomyopathy (DCM) with left ventricular (LV) dysfunction. Exclusion criteria: known cardiomyopathy, acute coronary syndrome, septic or anaphylactic or hypovolemic shock, treatment with angiotensin converting enzyme inhibitors (ACEI) or angiotensin II antagonists (AA II). OS was evaluated in blood samples at the admission (T0) and one month later: thiobarbituric acid-reactive substances (TBARS), total antioxidant status (TAS), protein carbonyls (PC) and LDL oxidized; superoxide dismutase (SOD), glutathione peroxidase(GSH and GSSG/GSH) and catalase activities; plasma α tocopherol, vitamin A and β carotene. Results 23 consecutive patients (90% men), mean age 59±11y. Follow-up of 15 months. The aetiologies of CMD were ischemic (n=6), idiopathic (n=15), toxic (n=1) or restrictive (n=1). The mean LV ejection fraction was 23.3±8%. The NT-proBNP level was 9600±2000ng/ml. To 1 MONTH NORMAL VALUE PC (μmol/g prot) 0.16 (0.05-0.41) 0.14 (0.07-0.29) < 0.10 TBARS (nmol/gHb) 2.2 (1.3-17.3) 2.5 (1.1-6.5) 0.7-1.6 LDLox (UI/L) 48 (20-83) 49 (26-98) 16-18 GSH (μmol/g Hb) 2.1 (0.8-3.1) 2.2 (1.7-4) 3.3-6.9 GSSG/GSH 0.19 (0.09-0.93) 0.13 (0.07-0.29) < 0.08 Full-size table Table options View in workspace Download as CSV Acute heart failure was associated with an increased OS. OS was more important in patients with arrhythmia. Conclusion Acute heart failure increased the level of oxygen free radicals. We hypothetized that modifications of OS could be implied in arrhythmias and complications of acute heart failure.