The Role of Metoprolol and Enalapril in the Prevention of Doxorubicin-induced Cardiotoxicity in Lymphoma Patients.

BACKGROUND/AIM: Anthracyclines, such as doxorubicin, though widely used in anticancer therapy, they are associated with cardiotoxic side-effects. The aim of this trial was to investigate long-term follow-up cardiotoxicity findings in patients treated with doxorubicin and concomitant metoprolol or enalapril 10 years earlier. PATIENTS AND METHODS: Overall, 147 patients were randomized into the treatment arms. A total of 125 patients treated with doxorubicin without evidence of heart disease at the start of chemotherapy were analyzed. They were followed-up for up to 10 years after treatment start. RESULTS AND CONCLUSION: A total of 47 patients completed the follow-up and 21 patients died, none due to cardiotoxicity events. Clinical signs of heart failure were not seen in any patients and no statistically significant differences between baseline and 10-year findings were seen for echocardiographic variables. No evidence of long-term cardiotoxicity was seen and nor metoprolol or enalapril offered an additional benefit.

Cardioprotective effect of metoprolol and enalapril in doxorubicin-treated lymphoma patients: a prospective, parallel-group, randomized, controlled study with 36-month follow-up.

Anthracyclines have contributed to a marked increase in survival in different types of cancer [1,2]. Unfortunately, they are associated with dose-dependent cardiotoxicity and heart failure (HF) [3­8]. Change to a weekly dosage schedule with slow infusions has been tested, a strategy that requires more frequent hospital visits and increased storage resources[7,9]. Liposomal anthracycline formulations with reduced drug exposure and lower plasma concentrations may still be cardiotoxic at higher cumulative doses [10]. Beta-blockers and angiotensin converting enzyme(ACE) inhibitors have been shown to reduce anthracycline-induced cardiotoxicity,but have not been tested in long-term prospective, randomized,controlled studies with well defined cardiotoxicity criteria and careful cardiac function monitoring [11­16]. We investigated doxorubicin-induced clinical or subclinical cardiotoxicity in lymphoma patients after concomitant prophylactic therapy with metoprolol or enalapril or no concomitant treatment. We examined whether cardiotoxicity was related to the treatment or any other variable. We found that HF was less frequent under concomitant treatment than no treatment, especially in the metoprolol group, but the differences were not significant. No association was found between the presence of cardiotoxicity and concomitant treatment or other variable apart of age that had a significant impact. The marginal benefit seen with metoprolol should be investigated further.

Left atrial systolic function in primary and familial amyloidosis: assessment from left atrial volume change.

The severity of left ventricular involvement may differ between primary (PA) and familial amyloidosis (FA). This study examined whether differences in left atrial (LA) systolic function are also present. Twenty-eight patients (18 men, 10 women, aged 59 +/- 12 years) with PA, 17 (11 men, 6 women, aged 40 +/- 11 years) with FA, and 25 normal controls (18 men, 7 women, aged 56 +/- 14 years) underwent transthoracic M-mode, two-dimensional, and Doppler echocardiography. Left atrial volumes were determined at mitral valve (MV) opening (maximal, Vmax), electrocardiographic P wave (onset of atrial systole, Vp), and MV closure (minimal, Vmin) from the apical two-and four-chamber views using the biplane area-length method. Left atrial systolic function was assessed with the LA active emptying volume (ACTEV) = Vp-Vmin and fraction (ACTEF) = ACTEV/Vp. The E/A ratio was increased (1.34 +/- 0.93 vs. 0.89 +/- 0.3), whereas deceleration time was decreased (168.1 +/- 33.7 vs. 196.2 +/- 34.2 ms) in PA compared with FA (p<0.05). Vmax and Vp were similar in PA and FA and greater than in the controls (46.6 +/- 14 vs. 40 +/- 11.4 vs. 27.1 +/- 6.3 cm3/m2, p<0.01, and 33.4 +/- 11.6 vs. 29.7 +/- 10.8 vs. 16.8 +/- 3.8 cm3/m2, p<0.01, respectively). The ACTEV was lower in PA and in the controls than in FA (6.7 +/- 2 vs. 6.2 +/- 2.2 vs. 8.5 +/- 3.3, respectively, p<0.05). The ACTEF was lower in PA than in FA and both were lower than those in the controls (20 +/- 5% vs. 28 +/- 7% vs. 36 +/- 11%, respectively, p<0.01). Despite a similar increase in LA volume, LA systolic dysfunction is more pronounced in PA than in FA. This is most likely due to the restrictive left ventricular physiology possibly associated with depressed LA contractility in the former.

Blood pressure elevation after phenylephrine infusion may adversely affect myocardial perfusion in patients with coronary artery disease.

BACKGROUND: Although blood pressure is a major determinant of myocardial oxygen-demand, little information is currently available regarding the changes in blood pressure (BP) during myocardial ischemia. Since BP elevation may cause left ventricular (LV) wall stress and an increase in oxygen demand, infusion of an alpha-adrenergic agonist, such as phenylephrine (PH), may provoke changes in myocardial perfusion in coronary artery disease (CAD) patients. As the effects of BP changes alone on myocardial perfusion have never been assessed by thallium-201 (Tl) scintigraphy, we investigated the effects of BP elevation after PH infusion, in order to study the hypothesis that pressure loading alone without increases in heart rate, may provoke transient impairment of regional myocardial perfusion, in CAD patients. PATIENTS AND METHODS: Forty-one (41) patients with angiographically documented CAD, aged 54+/-8 years, were included in our study. Each patient was given, without any complications, a PH (0.1 mg/ml) dose infused at a rate of 0.8 ml/mm, determined by a standardisation procedure and producing a mean blood pressure elevation of approximately 30% above baseline levels and a heart rate response to levels of no less than 50 bpm. One minute after the desired blood pressure and heart rate responses were reached, 2 mCi of Tl were injected and the PH infusion continued until the termination of the test. Tl scintigraphy was performed both 2 min after Tl injection and 4 h later, while the results were correlated to coronary angiography findings. RESULTS: PH scintigraphy produced 152 total defects. The mean perfusion defect size (%) was 14+/-12 and was directly related to the number of diseased vessels, i.e., 2% for one-vessel disease, 15% for two-vessel disease and 25% for three-vessel disease (P<0.05). The lowest percentage Tl activity values were 56+/-14 and were inversely related to the number of diseased vessels (P<0.01). The mean Tl lung counts/pixel values were 25+/-8 while it increased as the number of diseased vessels increased (P<0.01). The mean lung/heart ratio values were 0.31+/-0.08 while it increased as the number of diseased vessels increased (P<0.01). CONCLUSION: BP elevation after PH loading, produces a significant impairment of myocardial perfusion, that correlates well with the extend of angiographic findings.

Severe aortic stenosis and mitral regurgitation in a woman with systemic lupus erythematosus.

Libman-Sacks endocarditis complicating systemic lupus erythematosus has rarely been reported to cause hemodynamically significant valvular lesions. This report presents a case of severe aortic stenosis combined with severe mitral regurgitation associated with systemic lupus erythematosus in a young woman who died while on the quota list for surgery.