D. J. Van Veldhuisen

ESC guidelines for the diagnosis and treatment of acute and chronic heart failure 2008: the Task Force for the diagnosis and treatment of acute and chronic heart failure 2008 of the European Society of Cardiology. Developed in collaboration with the Heart Failure Association of the ESC (HFA) and endorsed by the European Society of Intensive Care Medicine (ESICM).

Authors/Task Force Members: Kenneth Dickstein (Chairperson) (Norway)*, Alain Cohen-Solal (France), Gerasimos Filippatos (Greece), John J.V. McMurray (UK), Piotr Ponikowski (Poland), Philip Alexander Poole-Wilson (UK), Anna Strömberg (Sweden), Dirk J. van Veldhuisen (The Netherlands), Dan Atar (Norway), Arno W. Hoes (The Netherlands), Andre Keren (Israel), Alexandre Mebazaa (France), Markku Nieminen (Finland), Silvia Giuliana Priori (Italy), Karl Swedberg (Sweden)

Cardiovascular Morbidity in Long-Term Survivors of Metastatic Testicular Cancer

PURPOSE To determine whether long-term survivors of metastatic testicular cancer have an increased risk of cardiovascular morbidity more than 10 years after chemotherapy. PATIENTS AND METHODS Eighty-seven patients treated with cisplatin-containing chemotherapy before 1987 who were in remission for at least 10 years and whose ages were </= 50 years at the time of analysis were evaluated for the occurrence of cardiovascular events. Sixty-two of 87 patients were additionally evaluated for cardiac damage and cardiovascular risk factors. Their cardiovascular risk profile was compared with that of 40 patients with comparable age and follow-up duration treated with orchidectomy only for stage I disease. RESULTS Major cardiac events were found in five (6%) of the 87 patients (age at time of event, 30 to 42 years; time after chemotherapy, 9 to 16 years): two with myocardial infarction and three with angina pectoris with proven myocardial ischemia. An increased observed-to-expected ratio of 7.1 (95% confidence interval, 1.9 to 18.3) for coronary artery disease, as compared with the general male Dutch population, was found. In addition, one patient experienced a cerebrovascular accident. Exercise ECG did not reveal cases of subclinical coronary artery disease. Echocardiography showed normal systolic left ventricular function in most patients, but diastolic left ventricular function was disturbed in 33% of the patients. Of 62 chemotherapy patients, 79% had hypercholesterolemia, 39% had hypertension, 25% still experienced Raynauds phenomenon, and 22% had microalbuminuria. Compared with patients with stage I disease, the chemotherapy patients had higher blood pressure and higher total cholesterol and triglyceride levels and were more insulin-resistant. CONCLUSION In long-term survivors of metastatic testicular cancer, we observed a significantly increased risk for occurrence of cardiac events accompanied by a persisting unfavorable cardiovascular risk profile. Accurate follow-up, focused on cardiovascular complications and aimed at intervention in these young cancer survivors, seems to be important.

The fibrosis marker galectin-3 and outcome in the general population

Abstract.  de Boer RA, van Veldhuisen DJ, Gansevoort RT, Muller Kobold AC, van Gilst WH, Hillege HL, Bakker SJL, van der Harst P (University of Groningen). The fibrosis marker galectin‐3 and outcome in the general population. J Intern Med 2012; 272: 55–64.

Prospective Evaluation of Early Cardiac Damage Induced by Epirubicin-Containing Adjuvant Chemotherapy and Locoregional Radiotherapy in Breast Cancer Patients

PURPOSE To evaluate prospectively the cardiotoxic effects of epirubicin-containing adjuvant chemotherapy in breast cancer patients. PATIENTS AND METHODS Patients (median age, 46 years; range, 28 to 55 years) were treated with five cycles of fluorouracil, epirubicin (90 mg/m2), and cyclophosphamide (FEC) (group I, n = 21) or with four cycles of FEC followed by high-dose chemotherapy consisting of cyclophosphamide, thiotepa, and carboplatin (group II, n = 19). Locoregional radiotherapy was applied subsequently. Cardiac evaluation was performed before chemotherapy (T0), 1 month after chemotherapy, 1 month after radiotherapy (T2), and 1 year after start of chemotherapy (T3). Left ventricular ejection fraction (LVEF) was determined by radionuclide ventriculography and diastolic function by echocardiography. Autonomic function was assessed by 24-hour ECG registration for heart rate variability (HRV) analysis. Time-corrected QT (QTc) was assessed and N-terminal atrial natriuretic peptide (NT-ANP) and brain natriuretic peptide (BNP) were measured as biochemical markers of cardiac dysfunction. RESULTS No patient developed overt congestive heart failure (CHF) and the mean LVEF declined from 0.61 at T0 to 0.54 at T3 (P =.001), resulting in an LVEF below 0.50 (range, 0.42 to 0.49) in 17% of the patients, whereas 28% had a decline of more than 0.10. Plasma NT-ANP levels increased gradually from 237 pmol/L at T0 to 347 pmol/L at T3 (P <.01), whereas plasma BNP levels increased from 2.9 pmol/L to 5.1 pmol/L (P =.04). Mean QTc increased from 406 msec at T0 to 423 msec at T3 (P <.01). No persistent alterations were found in diastolic function and HRV. CONCLUSION Relatively low doses of epirubicin in adjuvant chemotherapy for breast cancer results in mild subclinical myocardial damage demonstrated by a decline in LVEF, an increase in natriuretic peptide levels, and an increase in QTc, which may indicate a long-term risk of CHF.

Pregnancy and delivery in women after Fontan palliation.

Objectives: To evaluate the outcome of pregnancy in women after Fontan palliation and to assess the occurrence of infertility and menstrual cycle disorders. Design and patients: Two congenital heart disease registries were used to investigate 38 female patients who had undergone Fontan palliation (aged 18–45 years): atriopulmonary anastomosis (n  =  23), atrioventricular connection (n  =  5) and total cavopulmonary connection (n  =  10). Results: Six women had 10 pregnancies, including five miscarriages (50%) and one aborted ectopic pregnancy. During the remaining four live-birth pregnancies clinically significant complications were encountered: New York Heart Association class deterioration; atrial fibrillation; gestational hypertension; premature rupture of membranes; premature delivery; fetal growth retardation and neonatal death. Four of seven women who had attempted to become pregnant reported female infertility: non-specified secondary infertility (n  =  2), uterus bicornis (n  =  1) and related to endometriosis (n  =  1). Moreover, several important menstrual cycle disorders were documented. In particular, the incidence of primary amenorrhoea was high (n  =  15, 40%), which resulted in a significant increase in age at menarche (14.6 (SD 2.1) years, p < 0.0001, compared with the general population). Conclusion: Women can successfully complete pregnancy after adequate Fontan palliation without important long-term sequelae, although it is often complicated by clinically significant (non-)cardiac events. In addition, subfertility or infertility and menstrual disorders were common.

Early detection of anthracycline induced cardiotoxicity in asymptomatic patients with normal left ventricular systolic function: autonomic versus echocardiographic variables

OBJECTIVE To investigate left ventricular dysfunction in patients who had been treated with anthracycline based chemotherapy. METHODS Autonomic function was compared with left ventricular diastolic function in 20 asymptomatic women with normal systolic function (left ventricular ejection fraction (LVEF) > 0.50) treated for breast cancer with high dose anthracycline based chemotherapy, and 20 age matched healthy controls. Left ventricular diastolic function was assessed echocardiographically by measuring the early peak flow velocity to atrial peak flow velocity ratio, isovolumic relaxation time, and deceleration time. Heart rate variability analysis was assessed for time domain and frequency domain parameters. RESULTS The mean (SD) age of the patients was 45 (7) years and the mean LVEF was 0.59 (0.06). The time interval after the end of chemotherapy was 29 (27) months. One or more diastolic variables were abnormal in 50% of the patients. Heart rate variability was abnormal in 85% of patients. Mean values of both time domain and frequency domain parameters were decreased (p < 0.05), in particular the parasympathetic indices. CONCLUSIONS Autonomic impairment occurs in a large proportion of asymptomatic patients with normal systolic left ventricular function after high dose anthracycline based chemotherapy. In particular, heart rate variability analysis may be a sensitive tool to identify the first signs of cardiotoxicity in these patients.

Pregnancy, fertility, and recurrence risk in corrected tetralogy of Fallot.

Objective: To determine in women with surgically corrected tetralogy of Fallot the risk of pregnancy for mother and fetus, whether fertility was compromised, and the recurrence risk of congenital heart disease. Design: Data were collected from 83 patients through interviews and review of medical records. Results: In 29 patients 63 pregnancies were observed, of which 13 ended in an abortion. Fifty successful pregnancies were observed in 26 patients. During six successful pregnancies (12%) complications (symptomatic right sided heart failure, arrhythmias, or both) occurred. Both patients who developed symptomatic heart failure had severe pulmonary regurgitation. No clear relation between offspring mortality, premature birth or being small for gestational age, and cardiac characteristics of the mother was identified. Fifty seven patients were childless (41 (72%) voluntarily). Recurrence risk for congenital heart disease was 2.2%. Infertility was uncommon. Conclusions: Although complications did occur in five of 26 (19%) of the patients with a corrected tetralogy of Fallot, pregnancy was generally well tolerated in this largest report so far. No obvious predictors for maternal events or child outcome were determined, except for a possible relation between severe pulmonary regurgitation and symptomatic heart failure.

Telomere length loss due to smoking and metabolic traits

Human age‐dependent telomere attrition and telomere shortening are associated with several age‐associated diseases and poorer overall survival. The aim of this study was to determine longitudinal leucocyte telomere length dynamics and identify factors associated with temporal changes in telomere length.

Heart rate variability in left ventricular dysfunction and heart failure: effects and implications of drug treatment.

OBJECTIVE--To review the importance of heart rate variability analysis in left ventricular dysfunction and heart failure and to assess the effects of drug treatment. In patients with left ventricular dysfunction or heart failure, a low heart rate variability is a strong predictor of a low probability of survival. Because drug treatment in these patients has rapidly changed over the past two decades, the effect of these drugs on heart rate variability needs special attention. DESIGN--A study of published reports to give an overview of heart rate variability in patients with left ventricular dysfunction or heart failure and how it is affected by drug treatment. RESULTS--Analysis of heart rate variability provides an easily obtained early marker for progression of disease. It seems to be more closely related to the degree of neurohumoral activation than to haemodynamic variables. Cardiovascular drugs may either stimulate or inhibit the degree of neurohumoral activation, and the effects of pharmacological intervention can be closely monitored with this method. CONCLUSIONS--The analysis of heart rate variability, including spectral analysis, is a novel non-invasive way to obtain potentially useful clinical information in patients with reduced left ventricular function. The effects of drug treatment on heart rate variability are in general consistent with their long-term effects in left ventricular dysfunction and heart failure.

Epidemiology of heart failure in a community-based study of subjects aged ≥57 years: Incidence and long-term survival

Survival data from hospital‐based or clinical trial studies of patients with chronic heart failure (CHF) do not represent survival in community‐based settings.