Pharmaceutical Prevention and Management of Cardiotoxicity in Hematological Malignancies.

Modern treatment modalities in hematology have improved clinical outcomes of patients with hematological malignancies. Nevertheless, many new or conventional anticancer drugs affect the cardiovascular system, resulting in various cardiac disorders, including left ventricular dysfunction, heart failure, arterial hypertension, myocardial ischemia, cardiac rhythm disturbances, and QTc prolongation on electrocardiograms. As these complications may jeopardize the significantly improved outcome of modern anticancer therapies, it is crucial to become familiar with all aspects of cardiotoxicity and provide appropriate care promptly to these patients. In addition, established and new drugs contribute to primary and secondary cardiovascular diseases prevention. This review focuses on the clinical manifestations, preventive strategies, and pharmaceutical management of cardiotoxicity in patients with hematologic malignancies undergoing anticancer drug therapy or hematopoietic stem cell transplantation.

A very rare case of extranodal B-cell non-Hodgkin lymphoma presenting with adrenal and heart involvement.

We report an extremely rare case of extranodal B-cell NHL: DLBCL (diffuse large B-cell non-Hodgkin lymphoma), stage IVE, presenting with heart and bilateral adrenal involvement. On admission, adrenal and thorax imaging identified large bilateral adrenal masses and a 4.6 cm mass in the right atrium wall. An adrenal biopsy revealed the presence of a DLBCL, with triple expression of bcl2, bcl6, C-MYC(+70%). Following six cycles of systemic immunochemotherapy with R-DA-EPOCH, and high methotrexate dose for CNS prophylaxis a marked decrease of lymphoma infiltration was observed. The selection of the appropriate treatment modality can lead to profound response and improve patient's outcome.

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.

Chitinase-3-like protein-1 (YKL-40) before and after therapy in supraventricular arrhythmias.

BACKGROUND: The inflammatory glycoprotein chitinase-3-like protein 1 or YKL-40 has emerged as a potential biomarker of cardiovascular diseases, including atrial fibrillation (AFib). We sought to assess YKL-40 in a wide spectrum of supraventricular arrhythmias besides AFib in comparison with other inflammatory markers. METHODS: We determined serum levels of YKL-40, C-reactive protein (CRP) and IL-6 in 70 patients with AFib, atrial flutter, atrioventricular node reentry tachycardia or other supraventricular tachycardias before, immediately after therapy and 1 week after therapy; 20 healthy patients served as controls. Patients were subsequently followed for 6 months for arrhythmia recurrence. RESULTS: Baseline YKL-40 was significantly elevated in AFib patients [99.5 (65.5,194) ng/ml versus 47.2 (38.9,51.6) ng/ml in controls, P < 0.001], but not in patients with other arrhythmias. YKL-40 levels correlated positively with left atrial volume index (Spearman's rho = 0.853, P < 0.001). Its levels dropped significantly 1 week posttreatment only in AFib (P = 0.009 versus baseline); CRP and IL-6 remained practically stable throughout the study. Arrhythmia recurrence at 6 months occurred in 13 patients (19%), including 11 with AFib and 2 with atrial flutter. Baseline YKL-40 was independently associated with AFib recurrence (adjusted odds ratio = 1.02, 95% confidence interval = 1.00-1.04, P = 0.016). Neither CRP nor IL-6 was associated with AFib recurrence. CONCLUSION: Serum YKL-40 was elevated only in AFib and not in other supraventricular arrhythmias. In AFib, YKL-40 levels were responsive to therapy and predicted long-term recurrence.

Effect of functional electrical stimulation on cardiovascular outcomes in patients with chronic heart failure.

Background/design Functional electrical stimulation of lower limb muscles is an alternative method of training in patients with chronic heart failure (CHF). Although it improves exercise capacity in CHF, we performed a randomised, placebo-controlled study to investigate its effects on long-term clinical outcomes. Methods We randomly assigned 120 patients, aged 71 ± 8 years, with stable CHF (New York Heart Association (NYHA) class II/III (63%/37%), mean left ventricular ejection fraction 28 ± 5%), to either a 6-week functional electrical stimulation training programme or placebo. Patients were followed for up to 19 months for death and/or hospitalisation due to CHF decompensation. Results At baseline, there were no significant differences in demographic parameters, CHF severity and medications between groups. During a median follow-up of 383 days, 14 patients died (11 cardiac, three non-cardiac deaths), while 40 patients were hospitalised for CHF decompensation. Mortality did not differ between groups (log rank test P = 0.680), while the heart failure-related hospitalisation rate was significantly lower in the functional electrical stimulation group (hazard ratio (HR) 0.40, 95% confidence interval (CI) 0.21-0.78, P = 0.007). The latter difference remained significant after adjustment for prognostic factors: age, gender, baseline NYHA class and left ventricular ejection fraction (HR 0.22, 95% CI 0.10-0.46, P < 0.001). Compared to placebo, functional electrical stimulation training was associated with a lower occurrence of the composite endpoint (death or heart failure-related hospitalisation) after adjustment for the above-mentioned prognostic factors (HR 0.21, 95% CI 0.103-0.435, P < 0.001). However, that effect was mostly driven by the favourable change in hospitalisation rates. Conclusions In CHF patients, 6 weeks functional electrical stimulation training reduced the risk of heart failure-related hospitalisations, without affecting the mortality rate. The beneficial long-term effects of this alternative method of training require further investigation.

Myocardial deformation imaging unmasks subtle left ventricular systolic dysfunction in asymptomatic and treatment-naïve HIV patients.

BACKGROUND: Patients infected by the human immunodeficiency virus (HIV) and receiving highly active antiretroviral therapy have a higher incidence of cardiovascular disease than healthy subjects, but little is known about cardiac function in asymptomatic and treatment-naïve patients. We sought to study cardiac function in asymptomatic HIV-infected, treatment-naïve patients. METHODS: We studied 41 HIV-infected and treatment-naïve patients and 20 age- and sex-matched healthy controls. Patients with cardiac symptoms, history of cardiac disease or NT-proBNP >100 pg/mL were excluded. We addressed cardiac function using standard echocardiography along with tissue Doppler (TDI) measurements, including strain/strain rate assessment. RESULTS: Standard echocardiographic parameters did not differ between groups, except for transmitral E wave velocity (64.8 ± 14 cm/s in HIV vs 76.1 ± 10 cm/s in controls, p = 0.002). In contrast, TDI mitral and tricuspid annulus s velocity and all strain/strain rate measurements were significantly lower in HIV patients: s lateral, 10.2 ± 2.4/11.3 ± 0.7, p = 0.011; s septal, 8.1 ± 1.6/8.7 ± 0.8, p = 0.045; s tricuspid, 13.4 ± 2.3/14.9 ± 1.3, p = 0.002; strain/strain rate, septal (strain/strain rate, 15.1 ± 5.7/-0.9 ± 0.3, 25.3 ± 1.7/-1.9 ± 0.2, p < 0.001), anterior (16.7 ± 3/-1.0 ± 0.1, 26.7 ± 1.7/-1.9 ± 0.2, p < 0.001), lateral (16.0 ± 6/-1.0 ± 0.1, 27.5 ± 1.8/-2.2 ± 0.3, p < 0.001) and posterior (15.2 ± 5.8/-1.0 ± 0.2, 26.2 ± 1.8/-2.2 ± 0.3, p < 0.001) left ventricular wall. CONCLUSIONS: HIV infection itself is accompanied by subclinical systolic dysfunction, not apparent to standard echocardiography that can be unmasked though using sensitive echocardiographic techniques.

Diagnostic value of soluble adhesion molecule kinetics in patients with suspected myocardial ischemia undergoing dobutamine stress echocardiography.

INTRODUCTION: Previous studies have shown an exercise-induced increase in circulating adhesion molecules (sICAM-1 and sVCAM-1) in patients with coronary artery disease (CAD). The aim of this study was to evaluate the diagnostic role of changes in serum adhesion molecules in the setting of a dobutamine stress echocardiogram (DSE). METHODS: Thirty patients (18 men and 12 women aged 63.3 ± 10.67 years) with suspected myocardial ischemia underwent a DSE in our department's laboratory of echocardiography in order to identify inducible ischemia. Dobutamine was infused in incremental doses from 5 µg/kg/min up to 40 µg/kg/min. Blood samples were drawn at baseline as well as at peak stress and circulating adhesion molecules sVCAM-1 and sICAM-1 levels were measured by ELISA. Patients with a positive DSE underwent coronary arteriography within 2 weeks of the DSE study. RESULTS: Sixteen patients had a positive DSE for inducible ischemia while 14 had a negative test. Among the patients with positive DSE, 12 had angiographically significant CAD as well as statistically significantly higher levels of sICAM-1 than DSE negative patients (n=14), both at baseline (302.57 ± 43.37 vs. 267.47 ± 28.03 ng/mL, p=0.028) and at peak stress (322.07 ± 49.64 vs. 260.43 ± 36.45 ng/mL, p=0.001). A significant increase from baseline to peak stress was also noted in this group (from 302.57 ± 43.37 to 322.07 ± 49.64 ng/mL, p=0.043). There were no statistically significant differences in the levels of sVCAM-1 between groups at baseline and there was no change from baseline to peak stress. CONCLUSION: Plasma levels of sICAM-1 were found to be elevated in subjects with a positive DSE and angiographically significant CAD compared to patients with a negative DSE, both before and after inducible ischemia. In contrast, no changes were noted regarding sVCAM-1 levels.

Relation of ventricular tachycardia/fibrillation to beta-blocker dose maximization guided by pacing mode analysis in nonpacemaker-dependent patients with implantable cardioverter-defibrillator.

We hypothesized that uptitration of ß blockade and adjustment of pacing parameters to achieve a prevalence of single chamber atrial inhibited rate-responsive (AAIR) pacing in patients with dual-chamber implantable cardioverter--defibrillators (ICDs) would result in maximization of ß-blocker dosage and thus decrease appropriate ICD therapies. We included patients with ischemic or dilated cardiomyopathy and implanted ICDs without contraindications to ß blockers and atrioventricular conduction disturbances. Two 6-month periods were compared: clinically guided phase (pacing function set at back-up dual-chamber rate-responsive pacing mode at a lower rate of about 40 beats/min) and pacing-guided phase, during which ß-blocker dosage was titrated with a target of achieving >90% AAIR pacing (lower rate 60 beats/min). Sixty-one patients (64.2 ± 8.3 years old) were included. During the pacing-guided phase the target of ≥90% AAIR pacing was achieved in 80.3% of patients. Mean metoprolol dose during the clinically guided phase was 96.7 ± 29.4 versus 127.0 ± 39.6 mg/day in the pacing-guided phase (p <0.001). Appropriate ICD therapies were recorded in 35 patients (57.4%) during the clinically guided phase versus 20 (32.8%) during the pacing-guided phase (p <0.001; 1.15 and 0.48 appropriate ICD therapies per patient, respectively, p <0.001). In multivariate analysis, AAIR pacing and ß-blocker dose were inversely related to appropriate ICD therapies. In conclusion, a pacing-guided approach for maximizing ß-blocker doses guided by maximizing AAIR pacing in patients with ICDs may be beneficial compared to the conventional strategy. This pacing-guided approach led to higher daily ß-blocker doses, which were correlated to fewer appropriate ICD therapies.

Transradial access as first choice for primary percutaneous coronary interventions: experience from a tertiary hospital in Athens.

INTRODUCTION: The transfemoral approach (TFA) has been the mainstay for arterial access during percutaneous coronary intervention (PCI) in the setting of acute ST-segment elevation myocardial infarction (STEMI). However, the transradial approach (TRA) has been shown to be an equally effective and possibly safer way of performing primary PCI (pPCI). METHODS: The study population included 98 serially recruited patients who underwent pPCI in our institution. All patients were clinically followed during their hospital stay (6.4 ± 3.1 days). RESULTS: In the 98 patients included in the study, 65 procedures (66.3%) were completed via TRA, whereas the remaining 33 procedures (33.7%) used TFA. Door-to-balloon time was similar (57 ± 19 min vs. 54 ± 15 min, p=ns). Patients in the TRA group were mobilized sooner (28 ± 9 hours vs. 36 ± 13 hours, p<0.05). Hospital stay was significantly shorter in the TRA group (6.0 ± 3.2 days vs. 7.1 ± 2.8 days, p<0.05). TRA and TFA did not differ significantly as to the incidence of death, non-fatal myocardial infarction or subacute stent thrombosis, but major access-related vascular complications were significantly more frequent in the TFA group (2% vs. 15%, p<0.01). Cerebrovascular events did not differ between TRA and TFA. CONCLUSIONS: Compared to TFA, TRA seems to be associated with a lower incidence of bleeding complications, as well as earlier mobilization and discharge from hospital. It is conceivable that TRA could become the first choice in the treatment of STEMI patients in the near future, while TFA is kept as an alternative.

Evaluation of left ventricular hypertrophy in patients requiring permanent pacing.

OBJECTIVE: Hypertension may lead to left ventricular hypertrophy, fibrosis and degeneration of the conduction system. Our aim was to study the association of hypertrophy with certain arrhythmias such as complete atrioventricular block (AVB) and symptomatic sick sinus syndrome (SSS) that require implantation of permanent pacemaker. METHODS: We studied 130 patients that had been given a pacemaker because of complete AVB, 130 patients that had been given a pacemaker because of symptomatic SSS and 45 patients without cardiac conduction disturbances. In order to estimate left ventricular hypertrophy, indexes of relative wall thickness (RWT) and left ventricular mass (LVM) were evaluated by echocardiography. RESULTS: We observed significant association between complete AVB and abnormal values of echocardiographic indexes. CONCLUSIONS: Our results lend further support to the hypothesis that complete AVB is associated with left ventricular hypertrophy. This hypothesis is enhanced by the observation that the majority of patients with complete AVB were hypertensive.

Congenitally corrected transposition of the great arteries in a seventy-year-old woman.

Corrected transposition of the great arteries is a rare condition, and few patients with this abnormality survive past 50 years of age because of associated defects, or the subsequent development of atrioventricular valvular insufficiency or heart block or both. The case of our patient is of interest not only because she reached old age, but also because she lived a normal life, presenting with minor cardiac impairment and palpitations at the age of 70 years.