Pre-existing Cardiac Conditions Research Articles

What Keeps Patients with Subarachnoid Hemorrhage in the Neurosciences ICU?

Anticipated neurological intensive care unit length of stay is of interest to intensivists, administrators, patient families, neurologists, and neurosurgeons alike. Although some may equate length of stay with outcome, a measure more commonly addressed in the literature, these are two distinct entities. Patients with poor outcomes may have very brief lengths of stay as a result of early redirection of care, and thus, the issue of length of stay encompasses patients that, despite successful and aggressive care, may continue to serve as an ongoing challenge to intensivists. Intuitive neurological factors that prolong length of stay after aneurysmal subarachnoid hemorrhage include the vasospasm period and hydrocephalus. The severity of the former is influenced by patient age [1, 2], presenting clinical grade [3, 4], amount of subarachnoid blood [3, 4], and, as has been elegantly demonstrated by another recent post hoc analysis of CONSCIOUS-1, treatment modality [5]. However, the duration of the vasospasm period is not only influenced by these factors; it may also be influenced by varying vasospasm protocols as more aggressive approaches such as balloon angioplasty may shorten the period. At the conclusion of the vasospasm period, weaning of a ventriculostomy and/or placement of a shunt may be another factor prolonging ICU stay. Aside from neurological factors, medical conditions that arise as a result of subarachnoid hemorrhage such as severe myocardial stunning or neurogenic pulmonary edema may also prolong ICU stay. Of course, medical co morbidities in themselves particularly pre-existing cardiac conditions which may be stressed by the vasospasm period or respiratory conditions that may be stressed by altered mental status, pulmonary edema, pneumonia, and aggressive hydration may also prolong ICU stay. Of course, a long ICU stay in itself can ‘‘lengthen’’ ICU stay as a result of thromboembolic or infectious complications. However, many of these medical factors arise as time in the ICU passes and thus, to better counsel patient families and plan for aggressive care, early predictors of prolonged ICU stay are important to identify. Witiw and colleagues from the University of Toronto have performed an interesting post hoc analysis of patients in CONSCIOUS-1 [6] to elucidate factors on admission associated with prolonged length of stay after aneurysmal SAH. They found that age, clinical grade, pre-existing hypertension, intraparenchymal hemorrhage, and intraventricular hemorrhage were associated with prolonged critical care stays. Although increasing age may be protective from the perspective of vasospasm, it is intuitively deleterious from the perspective of arising medical co morbidities prolonging ICU stay and has sensibly arisen as a factor prolonging ICU stay. Clinical grade at presentation is a surrogate for hydrocephalus and is known to correlate with vasospasm [3, 4]—it is thus not at all surprising that this correlated with ICU length of stay as has been demonstrated in another smaller study [7]. As the authors only evaluated hypertension and hyperglycemia as potential presenting medical co morbidities, it is not surprising that associated-hypertension was significant, as this is likely a surrogate for other medical co morbidities that were not specifically evaluated. Intraventricular hemorrhage arising as a significant factor prolonging ICU stay is also sensible from the perspective of a greater proclivity toward ventriculostomy/shunt dependence. Interestingly, although ‘‘hydrocephalus’’ itself did not impact ICU stay in this B. A. Gross (&) Brigham and Women’s Hospital, Harvard Medical School, 75 Francis St, Boston, MA 02115, USA e-mail: bgross1@partners.org

Diesel Exhaust Inhalation Increases Cardiac Output, Bradyarrhythmias, and Parasympathetic Tone in Aged Heart Failure–Prone Rats

Acute air pollutant inhalation is linked to adverse cardiac events and death, and hospitalizations for heart failure. Diesel engine exhaust (DE) is a major air pollutant suspected to exacerbate preexisting cardiac conditions, in part, through autonomic and electrophysiologic disturbance of normal cardiac function. To explore this putative mechanism, we examined cardiophysiologic responses to DE inhalation in a model of aged heart failure-prone rats without signs or symptoms of overt heart failure. We hypothesized that acute DE exposure would alter heart rhythm, cardiac electrophysiology, and ventricular performance and dimensions consistent with autonomic imbalance while increasing biochemical markers of toxicity. Spontaneously hypertensive heart failure rats (16 months) were exposed once to whole DE (4h, target PM(2.5) concentration: 500 µg/m(3)) or filtered air. DE increased multiple heart rate variability (HRV) parameters during exposure. In the 4h after exposure, DE increased cardiac output, left ventricular volume (end diastolic and systolic), stroke volume, HRV, and atrioventricular block arrhythmias while increasing electrocardiographic measures of ventricular repolarization (i.e., ST and T amplitudes, ST area, T-peak to T-end duration). DE did not affect heart rate relative to air. Changes in HRV positively correlated with postexposure changes in bradyarrhythmia frequency, repolarization, and echocardiographic parameters. At 24h postexposure, DE-exposed rats had increased serum C-reactive protein and pulmonary eosinophils. This study demonstrates that cardiac effects of DE inhalation are likely to occur through changes in autonomic balance associated with modulation of cardiac electrophysiology and mechanical function and may offer insights into the adverse health effects of traffic-related air pollutants.

Preparticipation screening and prevention of sudden cardiac death in athletes: Implications for primary care

The purposes of this article are to explore the mechanism of sudden cardiac death (SCD) in young athletes and examine how preparticipation screenings help identify precipitating cardiac abnormalities. Electrocardiogram (ECG) testing has been implicated to play an important role in detecting subtle abnormalities that may cause SCD, but the routine implementation of this diagnostic tool remains a debate among experts. This report was compiled by reviewing the scientific literature on SCD in athletes, preparticipation exams, and current screening guidelines using CINAHL, MEDLINE, and PubMed search engines. Although the American Heart Association guidelines do not include ECG testing for preparticipation screenings, the implementation of routine ECG testing for preparticipation sports physicals is effective in preventing SCD in athletes. Primary care providers should be aware of current guidelines for screening patients for heart diseases that predispose them to SCD and their legal obligations to be sure these athletes are safe. The implementation of ECG testing will assist in the decision whether to disqualify an athlete from participation as a result of preexisting cardiac conditions, and ultimately preventing the untimely death of a young athlete.

Comparison between 155 cases of robotic vs. 150 cases of open surgical staging for endometrial cancer

ObjectiveTo compare the outcomes of 155 cases of endometrial cancer who had robot-assisted surgical staging to 150 open cases. MethodsRetrospective chart review of cases of endometrial cancer that underwent staging two different ways by two surgeons at an academic institution. ResultsMean age was 62.4years in the robotic arm and 65 (P=0.04) in the open arm. Mean body mass index was 34.5Kg/m2 in the robotic arm and 33Kg/m2 in the open arm (P=0.2). Pelvic and para-aortic lymph node dissection were performed in 94.8% and 67.7% of the robotic cases versus 95.3% and 74% of the open cases, respectively. Mean operative time was 127min in the robotic arm, and 141min in the open arm (P=0.0001). Mean lymph node count was 20.3 in the robotic arm, and 20 in the open arm (P=0.567). Mean estimated blood loss was 119ml in the robotic arm and 185 in the open arm (P=0.015). Mean hospital stay was 1.5days in the robotic arm, and 4days in the open arm (P=0.0001). The incidence of postoperative ileus (0.6% vs. 10.7%, P=0.0001), infections (5.2% vs. 24%, P=0.0001), anemia/transfusion (1.3% vs. 7.7%, P=0.005), and cardiopulmonary complications (3.2% vs.14.7%, P=0.003) was significantly lower in the robotic arm vs. the open arm. There was one death in the robotic arm attributed to pre-existing cardiac condition. ConclusionRobotic-assisted staging reaps the benefits of minimally invasive surgery without compromising the adequacy of the procedure. Dedication to the technique shortens the operative time.

Bortezomib-Induced Congestive Cardiac Failure in a Patient with Multiple Myeloma

Bortezomib therapy is known to be associated with neurological side effects and thrombocytopenia. Its cardiac side effects are however not well known. The patient, a 70-year-old woman, with a previous history of myocardial infarction and subsequent coronary stenting, was detected to have multiple myeloma stage IIIa. She was started on Inj. Bortezomib (1.3mg/m(2)) and Tab. Dexamethasone 40mg on a weekly basis. She showed good response to therapy. Three days after administration of the 22nd dose of bortezomib, she presented to the hospital with congestive cardiac failure. Echocardiography revealed a drop in the left ventricular ejection fraction from pretreatment levels of 45-50 to 25%. Patient was treated medically for left ventricular failure secondary to a suspected ischemic etiology. Coronary angiography revealed non-critical coronary artery disease with patent right coronary artery and left circumflex stents. The N-terminal pro-brain natriuretic peptide (NT-proBNP) levels that were initially raised 4,030pg/ml (<125pg/ml) declined to 2,280pg/ml a week later and subsequently normalized over the next 2weeks. The patient responded well to treatment and was then discharged. The left ventricular ejection normalized over the next 3months. Cardiac side effects of bortezomib are not well reported. Elderly patients and those with preexisting cardiac conditions could be at increased cardiovascular risk. Since this risk increases once a cumulative dose of 20mg/m(2) has been administered, patients need to be monitored more intensively once this threshold has been attained. Increased awareness of these cardiac side effects is necessary for patients' safety.

Spectrum of cardiovascular findings during pregnancy and parturition at a tertiary referral center

To analyze the spectrum of cardiovascular diseases occurring during pregnancy and delivery at a tertiary referral center. All patients presenting at our institution with pre-existing or first diagnosis of cardiac disease were recruited. Cardiac and obstetric complications and maternal and neonatal outcomes were recorded. Fifty-two pregnancies in 49 women, including three pregnancy terminations were analyzed. Cardiac lesions were congenital in 26 (53.1%) and acquired in nine (18.4%); six patients (12.2%) had cardiomyopathies, eight (16.3%) ar-rhythmic conditions. A total of 42 women (85.7%) had a pre-existing cardiac condition and seven (14.3%) presented with first manifestation. Overall 22 cardiac complications occurred: five in pregnancy, eight around parturition, nine during follow-up. They included >1 New York Heart Association functional class deterioration (n=5), congestive heart failure/cardiomyopathy (n=5), valve replacement (n=4), sustained arrhythmia (n=3), cerebral insult, aortic dissection, transplantation (one case each), and death (n=2). Mean gestational age at delivery was 36+6. The cesarean section rate was 77.5%; 31.6% were performed for cardiac indications. Obstetric complications happened in 23 pregnancies (46.9%). There was no perinatal loss; cardiac defects were diagnosed in 9.3% (n=5) of offspring. Cardiovascular diseases occurring during pregnancy and parturition comprise a heterogeneous spectrum of conditions. Established scores aid in the identification of high-risk patients; however, in our series 14.3% women had been healthy previously.

Clinical Significance of Cardiac Co-Morbidities and Risk Factors for Patients Treated with Imatinib.

AbstractAbstract 4490 Background:Imatinib is currently standard therapy for patients with success in Chronic Myeloid Leukemia (CML). Several instances of cardiac adverse events have been reported for patients while on therapy with imatinib. In many instances, these events occur in patients with pre-existing cardiac conditions. The aim of our study was to determine the occurrence of cardiac events in patients with CML treated with Imatinib, and the impact that cardiac risk factors and pre-existing cardiac conditions had on the risk of developing cardiac adverse effects. Methods:We reviewed the medical records of 51 patients with chronic phase CML who were treated with imatinib after failing prior therapies. For each patient we collected cardiac risk factors, pre-existing cardiac disease, pre-treatment EKG and echocardiogram (ECHO) readings, as well as post-treatment changes in EKG and ECHO findings. Results:Pre-existing cardiac conditions were found in 14 (27%) patients, including congestive heart failure in 2 (4%), myocardial infarction in 4 (8%), atrial fibrillation in 1 (2%), benign arrhythmias in 1(2%), aortic regurgitation in 1(2%), mitral valve prolapse in 1 (2%), mitral regurgitation in 1(2%), pericarditis in 1(2%), bradycardia in1(2%) and benign arrhythmia in 1(2%). Cardiac risk factors were present in 26 patients (51%), including smoking in 10 patients (20%), hypertension in 17 (33%), diabetes mellitus in 9 (18%), obesity in 2 (4%), hyperlipidemia in 5 (10%), stress (self-reported by patient or on anxiolytic therapy) in 5 (10%), alcohol in 11 (22%), atherosclerosis in 3 (6%), and positive family history for cardiac disease in 5 patients (9.8%). Cardiac events were noted in 19 patients (37%) of whom 11 (58%) had pre-existing cardiac conditions prior to initiating imatinib treatment and 14 patients (27%) had at least one cardiac risk factor. Congestive heart failure with clinical manifestations was seen in 9 patients (18%) with documentation of decreased ejection fraction on echocardiogram seen in 3 patients (6%) who had a decrease in LVEF from a median of 55% (range 50% to 72%) to a median of 45% (range 25% to 60%). Out of the patients who developed CHF while on treatment with imitanib, 3 patients (6%) had history of cardiac conditions (atrial fibrillation in 1 (2%), congestive heart failure in 2 (4%)). Myocardial infarction was documented in 3 patients (6%), one of which had prior myocardial infarction and pacemaker, another had history of mitral valve prolapse and hypertension; one patient had hypertension, diabetes mellitus and positive family history but no prior history of heart disease. Arrhythmia was seen in 3 patients (6%). Post-treatment EKG changes occurred in 14 patients (27%) including bradycardia, PAC's, PVC's, ST-T wave changes, tachycardia and other rhythm abnormalities. These changes were usually asymptomatic. Gated cardiac study done after a median of 63 months (range 29 to 83 months) after initiation of imatinib treatment showed EF below 60% in 9 patients (18%) with a median of 55% (range 36% to 59%). None of the patients died of cardiac conditions and none discontinued imatinib therapy because of cardiac events. Conclusion:Although cardiac events occur in some patients treated with imatinib, these are much more common among patients with pre-existing cardiac conditions and/or cardiac risk factors. These patients need to be monitored closely to minimize their risk and intervene early when new cardiac events arise. Disclosures:Cortes:novartis: Research Funding; BMS: Research Funding; Pfizer: Consultancy, Research Funding. Kantarjian:novartis: Research Funding; BMS: Research Funding. O'Brien:Novartis: Research Funding.

Cardiotoxicity of the Anticancer Therapeutic Agent Bortezomib

Recent case reports provided alarming signals that treatment with bortezomib might be associated with cardiac events. In all reported cases, patients experiencing cardiac problems were previously or concomitantly treated with other chemotherapeutics including cardiotoxic anthracyclines. Therefore, it is difficult to distinguish which components of the therapeutic regimens contribute to cardiotoxicity. Here, we addressed the influence of bortezomib on cardiac function in rats that were not treated with other drugs. Rats were treated with bortezomib at a dose of 0.2 mg/kg thrice weekly. Echocardiography, histopathology, and electron microscopy were used to evaluate cardiac function and structural changes. Respiration of the rat heart mitochondria was measured polarographically. Cell culture experiments were used to determine the influence of bortezomib on cardiomyocyte survival, contractility, Ca(2+) fluxes, induction of endoplasmic reticulum stress, and autophagy. Our findings indicate that bortezomib treatment leads to left ventricular contractile dysfunction manifested by a significant drop in left ventricle ejection fraction. Dramatic ultrastructural abnormalities of cardiomyocytes, especially within mitochondria, were accompanied by decreased ATP synthesis and decreased cardiomyocyte contractility. Monitoring of cardiac function in bortezomib-treated patients should be implemented to evaluate how frequently cardiotoxicity develops especially in patients with pre-existing cardiac conditions, as well as when using additional cardiotoxic drugs.

Complete heart block secondary to bortezomib use in multiple myeloma

Although rare, cardiac rhythm abnormalities have been documented with bortezomib use in clinical trials. These side effects must be recognized promptly by physicians of various specialties as well as pharmacists. Special attention is required in patients with liver function abnormalities, elderly and patients with pre-existing cardiac conditions. Prompt bortezomib withdrawal is essential in these cases as it may prevent dismal outcomes. This is the first report of a complete heart block caused by bortezomib in the setting of myeloma therapy outside a clinical trial. The author discusses further various heart rhythm and other autonomic nervous system abnormalities attributed to bortezomib in the existing literature.

The effect of tolterodine 4 and 8 mg on the heart rate variability in healthy subjects

To investigate the potential effect of tolterodine on the human heart rate variability (HRV). Oral antimuscarinic treatment for overactive bladder might significantly alter HRV, which is an important predictor for cardiac and all-cause mortality. Yet, little information exists regarding the influence of oral antimuscarinics on the HRV. Healthy female volunteers were randomly assigned to either placebo, tolterodine extended release (ER) 4 or 8 mg. Before and 4 h post treatment, a 10 min electrocardiogram (ECG) was recorded in supine position. Frequency domain and time domain analysis of both ECG measurements resulted in very low frequency (VLF), low frequency (LF), and high frequency (HF) data, the root mean square of differences of successive NN (= normal to normal, i.e. interval between two R-peaks) intervals (RMSSD), and the standard deviation of the NN intervals (SDNN). Thirty subjects (mean age: 23.7 ± 2.3 years) were investigated. Placebo caused no significant HRV changes. Tolterodine 4 mg significantly increased heart rate (HR) and significantly decreased VLF. Tolterodine 8 mg significantly decreased HF, VLF, RMSSD and SDNN and significantly increased HR and LF/HF ratio. The changes observed with 4 mg were not significantly different versus placebo, but 8 mg significantly increased LF/HF as compared to placebo. A single dose of 8 mg tolterodine ER, but not 4 mg seems to reduce resting HRV versus placebo in young healthy subjects. This might be particular relevant for patients with pre-existing cardiac conditions on daily overactive bladder drug treatment and should be further investigated in larger trials.

Short-Term Effects of Lisdexamfetamine Dimesylate on Cardiovascular Parameters in a 4-Week Clinical Trial in Adults With Attention-Deficit/Hyperactivity Disorder

To evaluate the short-term impact of lisdexamfetamine dimesylate on cardiovascular parameters in adults with attention-deficit/hyperactivity disorder (ADHD). Medically healthy adults (18-55 years of age) with DSM-IV-TR-defined ADHD were randomly assigned to placebo or 30, 50, or 70 mg/d of lisdexamfetamine dimesylate for 4 weeks between May and November 2006. Electrocardiograms, systolic and diastolic blood pressure, and pulse were assessed pretreatment and weekly thereafter. There were no significant differences for mean systolic or diastolic blood pressure in any lisdexamfetamine dimesylate dose group versus placebo. Changes in pulse from baseline to endpoint were 0.0, 2.8, 4.2, and 5.2 bpm in the placebo and lisdexamfetamine dimesylate 30, 50, and 70 mg/d groups, respectively (P < .05, all lisdexamfetamine dimesylate groups vs placebo). Post hoc pulse outliers (pulse > or = 100 bpm; any 1 event) ranged from 3.3% to 8.5% of subjects in the lisdexamfetamine dimesylate groups, and no subjects in the placebo group were pulse outliers (P < .05 for lisdexamfetamine dimesylate 50 mg vs placebo only). There were no clinically meaningful electrocardiogram abnormalities. Overall, 8.3% (35/420; safety population) of subjects had treatment-emergent cardiovascular adverse events, and 1.7% (7/420) withdrew from the study because of cardiovascular complaints. Cardiovascular adverse events with lisdexamfetamine dimesylate in these medically healthy adults were generally mild to moderate in severity. Lisdexamfetamine dimesylate had limited short-term effects on heart rate, blood pressure, and electrocardiogram parameters that were of minimal clinical concern. These findings support the relative safety of lisdexamfetamine dimesylate. However, considering the potential of outliers, it is advisable to monitor cardiovascular parameters in stimulant-treated patients. Interpretation of these findings is limited to patients with no preexisting cardiac conditions who are taking their medication as prescribed. clinicaltrials.gov Identifier: NCT00334880.

Cardiac drug use in pregnancy: safety, effectiveness and obstetric implications

Morbidity and mortality due to cardiovascular disease is increasing in pregnancy. The physiologic changes of normal pregnancy serve as a ‘stress test’ on the cardiovascular system. This may lead to the unmasking of a latent underlying cardiac condition or the new onset of maternal cardiovascular disease, with an attendant increase in adverse maternal and fetal outcomes. Some women with pre-existing cardiac conditions may be receiving medications that need to be altered during pregnancy owing to a risk of adverse effects on the developing fetus, but for most cardiac conditions, there are safe and effective treatment options. Women should be educated that abrupt discontinuation of cardiac medications during pregnancy usually poses a greater risk than the medications themselves, and a plan of judicious drug selection should be implemented (ideally prior to conception).

Patients at Risk of Complications ofStaphylococcus aureusBloodstream Infection

Staphylococcus aureus is one of the most common causative pathogens of bloodstream infections (BSIs). In approximately one-half of patients with S. aureus BSI, no portal of entry can be documented. This group of patients has a high risk of developing septic metastases. Similarly, patient populations at high risk of S. aureus BSI and BSI-associated complications include patients receiving hemodialysis, injection drug users, patients with diabetes, and patients with preexisting cardiac conditions or other comorbidities. One of the most severe complications of S. aureus BSI is infective endocarditis, and S. aureus is now the most common cause of infective endocarditis in the developed world. Patients with methicillin-resistant S. aureus BSI or infective endocarditis have higher rates of mortality, compared with patients with methicillin-susceptible S. aureus infection. Nasal carriage is the most important source of S. aureus BSI. Better eradication and control strategies, including nasal decolonization and more-active antibiotics, are needed to combat S. aureus BSIs.

Significant improvement of right ventricular function by imatinib mesylate in scleroderma-associated pulmonary arterial hypertension

Sirs: Pulmonary arterial hypertension (PAH) is a devastating disease that harbours a poor prognosis, particularly in patients with scleroderma-associated PAH. Although modern therapies such as endothelin receptor antagonists (ERA), phosphodiesterase type-5 inhibitors (PDE5i) and prostanoids have improved the clinical situation and outcome of affected patients [5], the current medical treatment of PAH is not satisfactory. Recent experimental data suggest that platelet-derived growth factor (PDGF) plays a pivotal role in the pathobiology of PAH by initiating and maintaining the underlying pulmonary vascular remodelling [9]. Consistently, inhibition of PDGF receptor (PDGFR) signalling by the tyrosine kinase inhibitor imatinib mesylate was recently shown to reverse PAH in animal models and to improve the clinical situation in selected patients [3, 7, 9, 10]. However, imatinib was also shown to exert significant cardiotoxicity in animals and humans through its inhibitory effect on the non-receptor Abelson tyrosine kinase (c-Abl) [4]. Further analyses of clinical studies revealed that congestive heart failure is a rare event in patients receiving imatinib therapy, but occurs more frequently in patients with pre-existing cardiac conditions [1]. The latter fact may be of particular significance in patients with PAH and impaired right ventricular function since the right ventricle responds particularly sensitive to hemodynamic and/or cardiotoxic impairment. In addition, patients with scleroderma-associated PAH harbour a lower right ventricular contractility as compared to those with idiopathic PAH [6].

Partial hydatidiform mole and coexisting live fetus with normal karyotype — The dilemma of management and diagnosis — Case report

Pregnancy is characterized by complex physiological changes of the cardiovascular system.B-type natriuretic peptides, represented by the bioactive molecule (BNP) and its inactive amino terminal fragment (NT-proBNP) are important biomarkers used in the management of the heart failure. Besides cardiac causes, BNP can grow in other noncardiac conditions such as pregnancy. The levels of natriuretic peptides during pregnancy have been the subject of multiple studies, whether it is a normal pregnancy, or there are pre-existing or developed cardiac conditions during pregnancy. It depends on the stage of pregnancy and comorbidities: obesity, preeclampsia, pre-existing cardiomyopathies or peripartum cardiomyopathy. High levels of NT-proBNP in pregnancy are associated with increased risk of cardiovascular events and involve careful supervision of pregnancy, including imaging procedures.

Cardiovascular Monitoring of Children and Adolescents With Heart Disease Receiving Medications for Attention Deficit/Hyperactivity Disorder

Over the past decade, concerns have been raised regarding the safety of a variety of psychotropic medications in children and adolescents, the appropriate selection of patients for therapy, and the indications for cardiovascular monitoring. In 1999, concerns over potential cardiovascular effects of psychotropic drugs, especially tricyclic antidepressants1,2 but including stimulants, prompted the American Heart Association (AHA) scientific statement “Cardiovascular Monitoring of Children and Adolescents Receiving Psychotropic Drugs.”3 At that time, no specific cardiovascular monitoring was recommended for the use of stimulant medications. Since that time, a constellation of circumstances have come together, necessitating a second look at this complicated issue. These circumstances include an increased awareness of the presence of attention deficit/hyperactivity disorder (ADHD) in the general population and in children with preexisting cardiac conditions; public concerns about the side effects and toxicities of medications, especially psychotropic medications in children; and regulatory factors and warnings issued by the US Food and Drug Administration (FDA) and by the pharmaceutical industry in response to the FDA. This writing group was convened in response to FDA concerns with regard to the safety of the ADHD drugs and with regard to the identification of children with underlying cardiovascular abnormalities. At a time when there is much discussion of the side effects of drugs and of the use of psychotropic drugs in children in the media and lay literature, it is particularly important for the medical profession to play a significant role in critically evaluating the use of stimulant medication in children, including those who may have undiagnosed heart disease and those who are known to have heart disease. The writing group for “Cardiovascular Monitoring of Children and Adolescents With Heart Disease Receiving Medications for Attention Deficit/Hyperactivity Disorder” reviewed the literature relevant to this topic since the last publication of the AHA scientific …

Heart Disease in Pregnancy. Second Edition.

Celia Oakley and Carole A. Warnes, eds 354 pages. Oxford, UK: Blackwell Publishing; 2007. $114.95. ISBN: 1-4051-3488-7 Oakley and Warnes’ second edition of Heart Disease in Pregnancy is a concise portable text that incorporates the views and practices of international experts to aid the reader in caring for the unique patient population of gravid women with heart disease. The highly readable text has a logical framework, starting with physiological changes in pregnancy and flowing through common, then rare, high-risk cardiovascular states. The chapters culminate in labor and delivery, with anesthetic approaches, then transition to the important issues of genetic counseling and contraception. Providing quick, easy access to information on basic physiology, disease states, and management strategies, it will be of interest to a very broad professional base. The first few chapters offer standard reviews of the response of the heart to pregnancy and physiological rather than pathological secondary changes in the physical examination. Cardiac testing during pregnancy is detailed. Importantly, the first pathology addressed is congenital heart disease, which has overtaken rheumatic valvular disease as the most common preexisting cardiac condition in women of childbearing age. The British perspective is illuminating, with subtle changes in nomenclature, …

Early nifurtimox-induced biochemical and ultrastructural alterations in rat heart

Nifurtimox (Nfx) and Benznidazole (Bz) are being used for the treatment of the acute phase of Chagas' disease. Recently, they were also considered for use in the indeterminate phase. Both the nitroheterocyclic drugs have serious toxic side effects. The mechanism of Nfx toxicity is associated with the formation of reactive oxygen species (ROS) generated during nitroreduction. Potential effects on cardiac function have not been established yet, despite the well-known cardiopathy often produced by the disease itself. We describe experiments testing some acute effects of Nfx on the male Sprague Dawley rat heart. Nifurtimox was present in the heart at 1, 3 and 6 h after intragastric (i.g) treatment. In vitro studies on Nfx microsomal and cytosolic nitroreductase activities showed that only the microsomal fraction had the ability to nitroreduce it. Cytochrome P450 and cytochrome P450 reductase would be involved in the process as suggested by their response to specific inhibitors. Nifurtimox increased the cardiac protein carbonyl content at 1 and 3 h and decreased the protein sulfhydryl content at 3 h. In addition, 24 h after treatment ultrastructural alterations such as marked cytoplasmic vacuolization, separation and loss of myofibrils and mitochondrial swelling were observed. Results suggest that Nfx administration might aggravate pre-existing adverse cardiac conditions. Human & Experimental Toxicology (2007) 26, 781 -788.

Congestive heart failure is a rare event in patients receiving imatinib therapy

AbstractA recent preclinical study suggested that imatinib may be cardiotoxic in some patients. We reviewed all reported serious adverse events of cardiac adverse events occurring in patients on clinical trials involving imatinib. Among 1276 patients enrolled, 22 (1.7%) were identified as having symptoms that could be attributed to systolic heart failure. The median age was 70 years (range, 49 to 83 years). The median time from start of imatinib therapy was 162 days (range, 2-2045 days). At the time these events were reported, 8 (0.6%) were considered possibly or probably related to imatinib. A total of 18 patients had previous medical conditions predisposing to cardiac failure: congestive heart failure (CHF; 6 [27%] patients), diabetes mellitus (6 [27%] patients), hypertension (10 [45%] patients), coronary artery disease (CAD; 8 [36%] patients), arrhythmia (3 [14%] patients), and cardiomyopathy (1 [5%] patient). Of the 22 patients, 11 continued imatinib therapy with dose adjustments and management for the CHF symptoms without further complications. Imatinib therapy as a causal factor of CHF is uncommon, mainly seen in elderly patients with preexisting cardiac conditions. Patients with previous cardiac history should be monitored closely and treated aggressively with standard medical therapy, including diuretics, if they develop symptoms suggestive of heart failure.

Activity of Rituximab plus Cyclophosphamide, Doxorubicin/Mitoxantrone, Vincristine and Prednisone in Patients with Relapsed MALT Lymphoma

Background: Various chemotherapeutic agents as well as the anti-CD20 antibody rituximab (R) have been tested in patients with mucosa-associated lymphoid tissue (MALT) lymphoma, but no standard chemotherapeutic regimen has emerged so far. Judging from the data obtained in various types of lymphoma, the activity of R appears to be enhanced by combination with chemotherapy. As no data on this topic exist for MALT lymphoma, we have retrospectively analysed our experience with R plus cyclophosphamide, doxorubicin/mitoxantrone, vincristine and prednisone (R-CHOP/R-CNOP) in patients with relapsed MALT lymphoma. Patients and Methods: A total of 26 patients were identified, 15 were administered R-CHOP while 11 patients were given R-CNOP due to age >65 years or pre-existing cardiac conditions. Cycles were repeated every 21 days, and restaging was performed after 4 cycles of therapy. In case of complete remission, 2 further cycles were administered for consolidation while patients achieving partial remission or stable disease after restaging were given 4 further courses. Results: A total of 170 cycles were administered to our patients (median 6, range 2–8). Twenty of the 26 patients (77%) achieved a complete remission and 6 (23%) a partial remission. Toxicities were mainly haematological, with WHO grade III/IV leukocytopenia occurring in 5 patients. After a median follow-up of 19 months (range 10–45), all patients are alive: 22 are in ongoing remission, while 4 have relapsed between 12 and 19 months after treatment. Conclusions: Our data demonstrate a high activity of R-CHOP/R-CNOP in relapsing MALT lymphoma irrespective of prior therapy.