bluuebunny/crossref_metadata_2025 huggingface dataset:
Predictors of Acute Treatment Response Among Patients With Cluster Headache
Authors: Schürks Markus , Rosskopf Dieter , De Jesus Janete , Jonjic Mira , Diener Hans‐Christoph , Kurth Tobias
Published: June 2007

Background.—Oxygen and triptans are drugs of first choice to abort cluster headache attacks. However, clinical predictors of treatment response are unavailable.

Objective.—We aimed to identify predictors of acute treatment response among patients with cluster headache.

Methods.—We investigated 246 cluster headache patients with available information on personal, headache, and lifestyle characteristics as well as effectiveness of acute medication use. We used logistic regression models to identify potential predictors of triptan and oxygen response.

Results.—Triptans were effective in 137 of the 191 users and oxygen in 134 of the 175 users. We only identified increasing age (OR 0.96, 95% CI 0.93–0.99; P= .013) as a negative predictor for triptan response, while nausea/vomiting (OR 0.41, 95% CI 0.18–0.91; P= .029) and restlessness (OR 0.09, 95% CI 0.01–0.66; P= .019) were negative predictors of oxygen response.

Conclusions.—Few clinical features seem to predict treatment nonresponse in cluster headache. More refined studies aiming at physiological and genetic characteristics seem promising in the future.
Association Between Migraine and the G1246A Polymorphism in the Hypocretin Receptor 2 Gene
Authors: Schürks Markus , Limmroth Volker , Geissler Ingrid , Tessmann Grietje , Savidou Irini , Engelbergs Jörg , Kurth Tobias , Diener Hans‐Christoph , Rosskopf Dieter
Published: June 2007

Background.—The hypocretin receptor 2 (HCRTR2) G1246A polymorphism has been associated with the risk for cluster headache. Since the hypothalamic hypocretin/orexin system projects throughout the nervous system and affects multiple vegetative functions including generation of rhythmicity, vasomotion, autonomic symptoms as well as modulation of nociception, it may also be linked with migraine.

Objective.—We thus sought to evaluate whether the HCRTR2 G1246A polymorphism is associated with the risk for migraine.

Methods.—We prospectively established a cohort of 146 unrelated patients with migraine. The control group consisted of 279 healthy volunteers. We genotyped patients and controls for the HCRTR2 G1246A polymorphism and examined an association with presence or absence of migraine.

Results.—Genotype and allele frequencies were not significantly different between migraine patients and controls (genotype distribution: χ2= 4.13, 2 df, P= .13; allele distribution: χ2= 0.9, 1 df, P= .34).

Conclusion.—Our study does not support a major contribution of the HCRTR2 G1246A polymorphism to the pathogenesis of migraine in contrast to its effects in cluster headache.
Diastolic Dysfunction in the Presence of Left Ventricular Systolic Dysfunction: Implications of ß‐Adrenergic Blocking Therapy
Authors: Kim Michael H. , Starling Mark R.
Published: June 2007

The contribution of left ventricular diastolic dysfunction to the impairment in overall left ventricular performance in patients with systolic dysfunction is underappreciated. This article summarizes the available data on diastolic dysfunction in patients with congestive heart failure in which the predominant abnormality was thought to be left ventricular systolic dysfunction. The prevalence and identification of diastolic abnormalities and their clinical relevance are addressed, particularly the role of β‐adrenergic blocking therapy. The potential benefits of β‐adrenergic blocking therapy to diastolic performance are discussed from both a hemodynamic and clinical standpoint, with the implication that diastolic performance and its modulation should be considered in future investigations.
Dofetilide in Patients with Congestive Heart Failure and Left Ventricular Dysfunction: Safety Aspects and Effect on Atrial Fibrillation
Authors: Møller Mogens , Torp‐Pedersen Christian T. , Køber Lars ,   on behalf of the Danish Investigators of Arrhythmia and Mortality on Dofetilide (DIAMOND) Study Group
Published: June 2007

Introduction. Atrial fibrillation is a frequent cause of worsening of symptoms in patients with congestive heart failure. The drugs currently available for maintenance of sinus rhythm all have major side effects.

Methods. In 34 Danish coronary care units, 1518 patients with congestive heart failure and reduced left ventricular systolic function were randomized to receive either placebo or a new class III antiarrhythmic drug, dofetilide. The dose of dofetilide was adjusted according to the presence of atrial fibrillation, the length of the QT interval, and renal function. Patients were continuously monitored electrocardiographically for the first 3 days of the study. The primary end point was all‐cause mortality and follow‐up was for at least 1 year.

Results. In the dofetilide/placebo groups, 311/317 patients died (41%/42%). The hazard ratio for dofetilide treatment was 0.95 (95% confidence interval, 0.81–1.11). Treatment with dofetilide reduced worsening of heart failure significantly (hazard ratio, 0.75; 0.63–0.89). After 1 year, 61% of patients with atrial fibrillation at the start of the study had converted to sinus rhythm on dofetilide, vs. 33% in the placebo group. After conversion to sinus rhythm, 78%/43% of patients in the dofetilide/placebo groups remained in sinus rhythm for at least 1 year. There were 25 instances (3%) of torsade de pointes ventricular tachycardia in the dofetilide group and none in the placebo group.

Conclusion. In patients with congestive heart failure, dofetilide can effectively convert atrial fibrillation to sinus rhythm and maintain sinus rhythm after conversion. Hospitalization for congestive heart failure is reduced. Dofetilide does not affect mortality.
Chronotropic Incompetence: A Case Report
Authors: Vandergoten Peter , Vijgen Johan , Timmermans Philippe , Dendale Paul
Published: June 2007

Chronotropic incompetence is generally defined as an inadequate heart rate response to exercise, but manifestations can vary. The incidence depends on underlying cardiac pathology and, to a lesser degree, on the cut‐off value of the predicted heart rate during exercise. Different pathologies induce chronotropic incompetence. Its presence indicates an adverse outcome and is strongly correlated with coronary artery disease. Treatment consists of rate‐responsive pacemakers; dual‐sensor, adaptive pacemakers are superior to single‐sensor, rate‐augmenting pacemakers. This case report illustrates the negative effect of chronotropic incompetence on daily activities and its amelioration by implantation of a rate‐responsive pacemaker.
Examination of Left Ventricular Contractile Reserve by Doppler Myocardial Imaging in Patients with Dilated Cardiomyopathy
Authors: Fülöp Tibor , Hegedüs Ida , Édes István
Published: June 2007

Detection of left ventricular contractile reserve by means of dobutamine stress echocardiography is a well known technique. The aim of the present study was to detect velocity changes during the administration of dobutamine, to establish if Doppler myocardial imaging is a suitable method for determining left ventricular contractile reserve, and to determine if the technique provides more information than traditional stress echocardiography. Twenty‐five patients (all males; mean age, 53.4 years) were examined for a clinical diagnosis of idiopathic dilated cardiomyopathy with a poor left ventricular systolic function (ejection fraction <30%). Doses of 5–10 and 20 mg/kg/min dobutamine were administered and elevated at 4‐minute intervals. Ejection fraction was calculated using the Simpson rule. The peak systolic and the early and late diastolic velocities were measured in the basal segment of the septum and the inferior wall at baseline and at full dose of dobutamine. Results indicated that peak systolic velocity increased significantly, both in the septum (0.11±0.03 vs. 0.20±0.05 m/sec; p=0.001) and in the inferior wall (0.10±0.05 vs. 0.17±0.06 m/sec; p=0.03). Late diastolic velocities also increased significantly, both in the septum (0.17±0.05 vs. 0.22±0.07 m/sec; p=0.01) and in the inferior wall (0.18±0.08 vs. 0.21±0.02 m/sec; p=0.01). There was a significant linear correlation between the relative increases in basal ejection fraction value and in peak systolic velocity upon dobutamine stimulation. Patients were divided into responders and nonresponders based on responses in either ejection fraction (25% relative increase) or peak systolic velocity (5 cm/s increase). This study concludes that 1) Doppler myocardial imaging is an adequate and simple technique to examine left ventricular contractile reserve; and 2) measurement of peak systolic velocity during dobutamine stimulation seems to be a simple and good indicator of left ventricular contractile reserve.
Clinic Dosing of β Blockers in Chronic Heart Failure
Authors: Ramahi Tarik M. , Rohlfs Kate , Sheynberg Natalie , Engle Katherine M. , Longo Marcella D.
Published: June 2007

Beta blockers improve survival and reduce morbidity of patients with chronic heart failure. Stringent dosing guidelines calling for a 1‐hour observation period after initiation or up‐titration of β‐blocker therapy might limit the use of β blockers and increase the expense involved. This study was conducted to determine the usefulness of this observation period. Data were collected from 130 inclinic postdosing observation periods for 34 stable chronic heart failure patients started on carvedilol. The mean left ventricular ejection fraction was 0.22±0.09, and the mean functional class was 2.5±0.6. No patient had greater than first‐degree heart block. Carvedilol was started at 3.125 or 6.25 mg b.i.d., and the dose was doubled every 1–3 weeks. All patients were observed for 1–2 hours after initiation or dosage increase, and blood pressure and heart rate were measured hourly. The maximal daily dose was 50±31 mg. In none of the observation periods was there a decrease in the dose of β blockers administered in the clinic. The predosing mean blood pressure was 110±15/71±10 mm Hg, and the mean heart rate was 78±13 bpm; the 1‐hour postdosing mean blood pressure was 101±14/67±10 mm Hg (p<0.001), and the heart rate was 78±13 bpm. The dose was decreased in six patients and medication was discontinued in three, all consequent to symptoms reported several days after dosage increase. Beta blockers can be safely initiated and up‐titrated at home in properly selected and evaluated stable patients with chronic heart failure and severe left ventricular dysfunction resulting in mild or moderate impairment of functional capacity.
Improving Heart Failure Care in the Office Setting
Authors: Miller Gayle L. , Mills Michelle A. , Havranek Edward P. , Taylor Jane P. , Ordin Diana L.
Published: June 2007

This column is the sixth in a series describing Health Care Financing Administration (HCFA) initiatives to improve care for Medicare beneficiaries with heart failure. The fourth column addressed the Heart Failure Practice Improvement Effort, HCFA's pilot project to test the feasibility of assessing and improving heart failure care in the outpatient setting through the activities of HCFA‐contracted peer review organizations in eight states. This column is dedicated to illustrating the progress of the Heart Failure Practice Improvement Effort project at an individual state and practice level, focusing on the quality improvement activities in outpatient heart failure care conducted by the Colorado peer review organization.
Left Ventricular Dysfunction Related to Septic Shock Masquerading as Postpartum Cardiomyopathy
Authors: Bukharovich Inna F. , Harrison Ellen , Le Jemtel Thierry H.
Published: June 2007

Peripartum cardiomyopathy, an uncommon cause of chronic heart failure, may present during the third trimester of pregnancy, but most often develops within 2 months postpartum. The etiologies of heart failure during pregnancy and postpartum are numerous, however. The authors describe the case of a 25‐year‐old woman who developed severe, symptomatic heart failure following delivery and discuss their initial consideration of peripartum cardiomyopathy and the differential diagnostic features of this case.
Relation of Functional Capacity With the Oxidative Stress and Antioxidants in Chronic Heart Failure
Authors: Serdar Akin , Yesilbursa Dilek , Serdar Zehra , Dirican Melahat , Turel Baybars , Cordan Jale
Published: June 2007

Chronic heart failure is a common, disabling disorder with high mortality. Oxidative stress may have both functional and structural effects on the myocardium, leading to myocardial decompensation. In this study, the authors examined the relationship of oxidative stress and functional capacity in patients with varying degrees of heart failure. Fifty‐one patients with chronic heart failure and 31 control subjects were studied. The functional capacity of patients was determined. Plasma malondialdehyde, vitamin E, and β‐carotene levels were measured. The malondialdehyde levels were significantly different between control subjects and heart failure patients (p=0.03). There was a positive correlation between patients' malondialdehyde levels and New York Heart Association functional class (r=0.59; p<0.0001). There was a negative correlation between the functional class and vitamin E and β‐carotene levels (r=−0.43; p<0.0001 and r=−0.25; p<0.01, respectively). These data demonstrate that oxidative stress is increased systemically in patients with chronic heart failure. It seems that this increase correlates with functional class.
Novel Diagnostic Markers in Heart Failure: An Emerging Paradigm Shift?
Authors: Grant Arthur “Chip” , Uber Patricia A. , Park Myung H. , Scott Robert L. , Mehra Mandeep R.
Published: June 2007

The differential diagnosis of dyspnea can be overwhelming in the presence of competing diseases. The recent advent of the peptide marker brain natriuretic peptide has ushered in an era of refined diagnostic capability in heart failure. We present a clinical scenario to illustrate the usefulness of this new biomarker assay in directing appropriate therapy for heart failure.
Role of Echocardiography in the Assessment of Left Ventricular Thrombus Embolic Potential After Anterior Acute Myocardial Infarction
Authors: Domenicucci Stefano , Chiarella Francesco , Bellone Pietro
Published: June 2007

The contribution of cardiac ultrasound in assessment of the embolic potential of left ventricular thrombi after anterior acute myocardial infarction was verified in a prospective study of serial echocardiograms (mean, 18.9 examinations per patient) obtained over a long‐term period (1–72 months; mean, 38±12). The study population comprised 222 patients (162 men; age, 64±11 years) with a first anterior acute myocardial infarction, treated with thrombolysis (group A) or receiving no antithrombolic therapy (group B). Embolism occurred in a total of 12 patients (11 with a left ventricular thrombus; p<0.005) and was more frequent in group B (10 patients; p<0.04). Predictors of embolism were the absence of thrombolysis, detection of a left ventricular thrombus, protrusion or mobility of the thrombus, and morphologic changes in the thrombus over time. Patients in group A had a lower incidence of each of these predictors, and a higher thrombus resolution rate. An appropriate echocardiographic protocol is crucial to assessment of the embolic potential of left ventricular thrombi after anterior acute myocardial infarction and may help to identify candidates for aggressive antithrombotic therapy.
Ambulatory Blood Pressure Monitoring: Technique and Application in the Study of Cardiac Dysfunction and Congestive Heart Failure
Authors: Mansoor George A. , Abiose Ademola , White William B.
Published: June 2007

Ambulatory blood pressure monitoring has become a widely used method of blood pressure and heart rate evaluation in the free‐living subject. Recently, ambulatory monitoring has become covered by Medicare for the evaluation of “white‐coat” hypertension. Although the technique provides only intermittent readings throughout the 24‐hour period, average blood pressures obtained in this way correlate well with a variety of hypertensive disease processes and are also a better prognostic marker for future cardiovascular events than office blood pressure. Ambulatory blood pressure averages also correlate well with indices of diastolic dysfunction. In patients with congestive cardiac failure and systolic dysfunction, ambulatory monitoring suggests an impaired circadian blood pressure profile with high nocturnal blood pressure. Further research is needed on the relationship between ambulatory blood pressure and cardiac dysfunction, as well as the impact of observed circadian blood pressure changes on outcome.
Lessons Learned From the National Heart Failure Project: A Center for Medicare & Medicaid Services Initiative to Improve the Care of Medicare Beneficiaries With Heart Failure
Authors: Havranek Edward P. , Masoudi Frederick A. , Smith Grace L. , Wolfe Pam , Ralston Debra L. , Krumholz Harlan M. , Ordin Diana L.
Published: June 2007

This column is the seventh in a series reporting on the efforts of the Center for Medicare and Medicaid Services (CMS), formerly known as the Health Care Financing Administration, to improve care for Medicare beneficiaries with heart failure. In previous columns we have described the overall structure of Medicare quality improvement efforts, detailed the structure of the national inpatient fee‐for‐service program known as the National Heart Failure project, and discussed the baseline quality indicator rates for the project, which are focused on rates of ejection fraction documentation and angiotensin‐converting enzyme inhibitor prescription. In more recent columns, we reported on quality improvement projects from several participating hospitals, and on a pilot project exploring quality improvement efforts for heart failure based in physicians' offices. This column will focus on ways in which systematic examination of data, such as those from the National Heart Failure project, might shape future quality improvement and research efforts. The National Heart Failure project's quality indicator data are collected primarily to guide and evaluate the efforts of the CMS contractor peer‐review organizations to facilitate quality improvement efforts in hospitals throughout the United States.
Severe Hypocalcemia: A Rare Cause of Reversible Heart Failure
Authors: Mikhail Nasser , El‐Bialy Adel , Grosser Jeremy
Published: June 2007

Despite the crucial role of calcium in myocardial contractility, hypocalcemia has been rarely reported as a cause of heart failure. In this article, the authors describe a case of severe hypocalcemia caused by idiopathic hypoparathyroidism and worsened by concomitant hypomagnesemia. The patient presented with congestive heart failure that improved dramatically with amelioration of plasma calcium levels. This case and other similar cases in the literature revealed that hypocalcemic heart failure is reversible. Measurement of plasma calcium should be included in the initial work‐up of all patients with heart failure, and plasma magnesium must also be checked and corrected if hypocalcemia is demonstrated.
Successful Weaning from Milrinone of a Patient with Severe Congestive Heart Failure Using Carvedilol
Authors: Delgado Reynolds M. , Eastwood Cathy A. , Jax Thomas
Published: June 2007

Congestive heart failure is a major and growing health care concern worldwide, and mortality in patients with severe heart failure is high. Few options are available to patients with New York Heart Association Class IV heart failure refractory to oral medical therapy. Over the last 15–20 years milrinone, a phosphodiesterase‐III inhibitor, has been used occasionally to treat patients with acute heart failure and as a bridge to heart transplantation and, more recently, has been used intermittently or continuously on an outpatient basis. We report a patient with severe, chronic congestive heart failure, whom we treated successfully with continuous milrinone infusions as an outpatient. We were able to wean him of the milrinone after successful up‐titration of carvedilol. Nine months after discontinuation of milrinone the patient remains stable in New York Heart Association Class I on high dose carvedilol. Research is required to validate the possibility that patients with severe heart failure may be successfully weaned from milrinone using carvedilol and achieve significant improvement of their functional status and quality of life. This may prove to be an effective strategy for the treatment of selected patients with severe, chronic congestive heart failure.
Baseline Quality Indicator Rates from the National Heart Failure Project: A HCFA Initiative to Improve the Care of Medicare Beneficiaries with Heart Failure
Authors: Masoudi Frederick A. , Ralston Debra L. , Wolfe Pam , Havernek Edward P. , Shah Vimal P. , Krumholz Harlan M. , Ordin Diana L.
Published: June 2007

This column is the third in a series reporting on Health Care Financing Administration (HCFA) initiatives to improve care for Medicare beneficiaries with heart failure. The first paper1 outlined the history of HCFA quality improvement projects and current initiatives to improve care in six priority areas: heart failure, acute myocardial infarction, stroke, pneumonia, diabetes, and breast cancer. The second2 reported in more detail the structure of the national inpatient fee‐for‐service heart failure initiative, known as the National Heart Failure project. It described the development of the quality indicators, the sampling strategy for selecting charts to be reviewed, and the types of local efforts spurred by the project through the activities of each state's HCFA contractor peer review organization. This article discusses baseline quality indicator rates from the National Heart Failure project.
Balancing Diuretic Therapy in Heart Failure: Loop Diuretics, Thiazides, and Aldosterone Antagonists
Authors: Paul Sara
Published: June 2007

In heart failure, sodium is retained by the kidneys despite increases in extracellular volume. There is activation of renin secretion, which culminates in the production of angiotensin II, causing vasoconstriction and aldosterone secretion. These synergistically produce an increase in tubular reabsorption of sodium and water. Diuretics are the mainstay of symptomatic treatment to remove excess extracellular fluid in heart failure. Diuretics that affect the ascending loop of Henle are most commonly used. Thiazide diuretics promote a much greater natriuretic effect when combined with a loop diuretic in patients with refractory edema. Recently, spironolactone, an aldosterone receptor blocking agent, has been recommended to attenuate some of the neurohormonal effects of heart failure. Regardless of the diuretic, patients need to be counseled on the importance of avoiding sodium in their diet
Oxidative Stress and Endothelial Dysfunction in Heart Failure
Authors: Sharma Rajesh , Davidoff Madalyn N.
Published: June 2007

The clinical syndrome of congestive heart failure (CHF) is characterized by abnormalities of left ventricular function and neurohormonal regulation, which are accompanied by effort intolerance, fluid retention, and decreased longevity. While an increased sympathetic tone and an activated renin‐angiotensin system may contribute to the reduced vasodilatory capacity in patients with CHF, the important role of the endothelium in coordinating tissue perfusion has now been recognized. CHF is associated with endothelial dysfunction, as demonstrated by impaired endothelium‐mediated vasodilation. Endothelial dysfunction in patients with CHF is a critical component in the systemic vasoconstriction and reduced peripheral perfusion that characterizes these patients. Endothelial regulation of vascular tone is mediated mainly by nitric oxide. Increased oxidative stress in patients with CHF is likely caused by decreased bioavailability of nitric oxide due to reduced expression of endothelial nitric oxide synthase and increased generation of reactive oxygen species. These react with nitric oxide in the setting of decreased antioxidant defenses that would normally clear these radicals, culminating in attenuated endothelium‐dependent vasodilation in patients with CHF. Therapies that improve endothelial function have been shown to improve exercise tolerance and outcomes in patients with CHF. Endothelial dysfunction is thus an important target for future therapy in patients with CHF.
Reactive Oxygen Species, Mitochondria, and NAD(P)H Oxidases in the Development and Progression of Heart Failure
Authors: Sorescu Dan , Griendling Kathy K.
Published: June 2007

Reactive oxygen species (ROS) released acutely in large amounts have been traditionally implicated in the cell death associated with myocardial infarction or reperfusion injury. These ROS can be released from the cardiac myocyte mitochondria, xanthine oxidase, and the phagocytic nicotinamide adenine dinucleotide phosphate (NAD(P)H) oxidase. Interestingly, the chronic release of ROS has been recently linked to the development of left ventricular hypertrophy and heart failure progression. The chronic release of ROS appears to derive from the nonphagocytic NAD(P)H oxidase and mitochondria. Experimental data are accumulating suggesting that the release of ROS is required for the normal, physiologic activity of cardiac cells, but abnormal activation of the nonphagocytic NAD(P)H oxidase in response to neurohormones (angiotensin II, norepinephrine, tumor necrosis factor‐α) has been shown to contribute to cardiac myocyte hypertrophy. Furthermore, the fibrosis, collagen deposition, and metalloproteinase activation involved in the remodeling of the failing myocardium are dependent on ROS released during the phenotypic transformation of fibroblasts to myofibroblasts associated with progression of end‐stage heart failure. Future studies are necessary to identify the sources, mechanisms of activation of NAD(P)H oxidases, and downstream signaling targets implicated in the progression of chronic heart failure.
Genetic Polymorphisms and Oxidative Stress in Heart Failure
Authors: Alameddine Fadi M.F. , Zafari A. Maziar
Published: June 2007

Heart failure results from various known cardiovascular diseases, such as coronary artery disease, or can be the result of an idiopathic dilated cardiomyopathy. It is of utmost importance for diagnostic, preventive, and therapeutic purposes to understand the cellular events that trigger the cascade of functional and structural changes that result in the development and progression of heart failure. Progress in unraveling the genetic background in both ischemic and nonischemic cardiomyopathies has been slow compared with that for monogenic diseases, such as some forms of hypertrophic cardiomyopathy or familial dilated cardiomyopathies. It is likely that susceptibility to and risk of progression of heart failure are both influenced by many genes acting in concert or independently. Among the diverse Subcellular mechanisms implicated in the pathogenesis and progression of heart failure, reactive oxygen species play a major role. The search for genetic polymorphisms in clinical association studies in order to identify genotypes susceptible to develop and affect the progression to heart failure has been the focus of many investigations over the past several years. In this review, the authors summarize the current data in support of the role of various polymorphisms of genes related to oxidative stress in the susceptibility to develop heart failure, and its progression.
Natriuretic Peptides and Salt Sensitivity: Endocrine Cardiorenal Integration in Heart Failure
Authors: Villarreal Daniel , Freeman Ronald H. , Reams Garry P.
Published: June 2007

Mammalian hearts contain a family of peptides with potent natriuretic, diuretic, and vasorelaxant actions. In addition to atrial natruretic peptide (ANP) and brain natriuretic peptide, recent studies in humans and animals have suggested that the N‐terminal ANP prohormone fragment 31–67 may represent another adaptive mechanism to achieve body fluid homeostasis. Furthermore, these investigations have also suggested that via different mechanisms of action on target organisms, the C‐terminal hormone ANP 99–126 and pro‐ANP 31–67 may coordinate and contribute to the regulation of hemodynamic and renal function in pathophysiologic situations, such as heart failure.
Amiodarone Lung Injury: Another Heart Failure Mimic?
Authors: Sangha Sumandeep , Uber Patricia A. , Mehra Mandeep R.
Published: June 2007

Careful thought must be given to the development of bystander pathology that could mimic worsening of heart failure. Recent trials with patients receiving amiodarone record a low rate of amiodarone pulmonary toxicity of 1.6%. Bronchoalveolar lavage in amiodarone toxicity demonstrates an absolute and relative lymphocytic alveolitis, suggesting hypersensitivity, but this finding is neither sensitive nor specific. Recently, KL‐6, a mucin‐like high molecular weight glycoprotein secreted by proliferating type II alveolar pneumocytes, has been identified as a potential marker of interstitial pneumonitis. A high index of suspicion combined with rapid exclusion of common confounding mimics can help in establishing the diagnosis of amiodarone lung toxicity.
Neonatal Congenital Heart Disease and “Complex” Heart Failure
Authors: Berman Adam E. , Roca Theresa , Uber Patricia , Mehra Mandeep
Published: June 2007

Hypoplastic left heart syndrome is a complex conglomerate of congenital cardiac abnormalities encountered in early life. Heart failure compensation and survival are intricately dependent on maintenance of ductal patency and avoidance of hyperoxic ventilation. While medical therapy is woefully inadequate, the staged Norwood procedure or cardiac transplantation remain the better options for treatment. Critically dependent on surgical outcomes, 5‐year survival appears better with cardiac transplantation.
The Challenge of Neurocognitive Dysfunction in Severe Heart Failure
Authors: Sangha Sumandeep S. , Uber Patricia A. , Park Myung H. , Scott Robert L. , Mehra Mandeep R.
Published: June 2007

Often ignored, neurocognitive dysfunction in chronic heart failure represents a daunting morbidity progressing to loss of self‐reliance. Although the precise mechanisms arbitrating the development of this disorder remain elusive, microembolization and cerebral hypoperfusion are implicated. Other causes of cognitive decline may include prior cardiac surgery, chronic hypertension, sleep disordered breathing, hyperhomocysteinemia, dementia of aging, and more “traditional causes” such as Alzheimer's disease. The discovery of neurocognitive defects in heart failure must prompt a well‐constructed diagnostic evaluation to search for the underlying causes since this process may be at least partially reversible in many cases.
“BNP” for Heart Failure: Role of Nesiritide in Cardiovascular Therapeutics
Authors: Mills Roger M. , Hobbs Robert E. , Young James B.
Published: June 2007

B‐type natriuretic peptide, or nesiritide, recently gained US Food and Drug Administration approval as the first new parenteral agent approved for heart failure therapy in more than a decade. Nesiritide refers to a peptide identical to endogenous B‐type natriuretic peptide, currently manufactured by recombinant DNA technology. Nesiritide has been evaluated in clinical trials involving more than 700 subjects. The drug produces a prompt fall in systemic vascular resistance and pulmonary capillary wedge pressure, associated with rapid clinical improvement in decompensated heart failure. Nesiritide represents an attractive choice for “first‐line therapy” of acutely decompensated heart failure patients. In this review, the authors summarize the currently available data regarding the use of nesiritide, and offer recommendations for its use based on our experience with the compound in clinical trials.
Beta‐Adrenergic Blockade 2002: A Pharmacologic Odyssey in Chronic Heart Failure
Authors: Hermann Denise D.
Published: June 2007

The treatment for heart failure has evolved considerably during the past two decades. Initially focused on hemodynamic derangement, diuretics and vasodilator agents were employed for symptomatic management. Beta blocking agents, with intrinsic negative inotropic activity, were considered specifically contraindicated. Neurohormonal activation subsequently became recognized and validated as a self‐perpetuating influence on chronic heart failure and progressive adverse ventricular remodeling. Antagonism of the renin‐angiotensin‐aldosterone axis produced significant survival benefits in chronic heart failure populations. Concomitant intense sympathetic nervous system activation remained an additional therapeutic target. Pathophysiologic insights revealed a biologically plausible framework for the use of β blocking agents in heart failure. This review summarizes the major clinical trials of β blockers in heart failure populations with systolic left ventricular dysfunction. These trials support the integration of β blockade as a critical component of standard therapy for chronic heart failure. Ongoing trials and unresolved issues are also discussed.
Mitral Valve Surgery: When Is It Appropriate?
Authors: Badhwar Vinay , Bolling Steven F.
Published: June 2007

Mitral regurgitation (MR) is a frequent complication of end‐stage cardiomyopathy. Historically, these patients were managed either medically or with mitral valve replacement, both associated with poor outcomes. We studied 150 patients with cardiomyopathy and severe MR who were managed with mitral reconstruction. One hundred fifty patients with 4+ MR, left ventricular ejection fractions of 8%−24% (mean, 14%), and New York Heart Association class III or IV symptoms were prospectively studied. All patients underwent mitral valve repair with an undersized, flexible annuloplasty ring. There was one intraoperative death and seven 30‐day mortalities. Intraoperative echocardiography revealed no residual MR in the majority of patients and mild to trivial MR in seven patients. There were 27 late deaths; three of these patients had progression of the disease and underwent transplantation. The 1‐, 2‐, and 5‐year actuarial survival rates are 82%, 71%, and 57%, respectively. New York Heart Association class has improved for all patients, from a preoperative mean of 3.2±0.2 to 1.8±0.4 postoperatively. At 24‐month follow‐up, all patients showed improvement in ejection fraction, cardiac output, and end‐diastolic volumes, along with a reduction in the sphericity index and regurgitant volume. Mitral valve repair with an undersized, flexible annuloplasty ring is a safe and effective approach to correction of MR, even in cardiomyopathy patients. All observed changes contribute to reverse remodeling and the restoration of the normal left ventricular geometric relationship. Mitral reconstruction provides a new first‐line management strategy for patients with MR and end‐stage heart failure.
Future Challenges in Quality Improvement in Heart Failure
Authors: Havranek Edward P. , Masoudi Frederick A. , Ralston Debra L. , Susman Nancy J. , Krumholz Harlan M. , Taylor Jane P.
Published: June 2007

This is the final installment in a series reporting on the Centers for Medicare & Medicaid Service's (CMS) initiatives to improve care for Medicare beneficiaries with heart failure through its Quality Improvement Organization (QIO) contractors during the 1999–2002 contract cycle. Previous columns have reported on a nationwide hospital‐based effort, the National Heart Failure project, and a more limited outpatient‐based effort, the Heart Failure Practice Improvement Effort. After 3 years of experience with the National Heart Failure project, it is appropriate to highlight the issues pertinent to future quality improvement initiatives in heart failure care.
Effective Observation Unit Treatment of Decompensated Heart Failure
Authors: Peacock William Franklin , Remer Erica E. , Aponte Josef , Moffa Donald A. , Emerman Charles E. , Albert Nancy M.
Published: June 2007

There is little information on the effectiveness of emergency department (ED) observation unit (OU) heart failure (HF) therapy. The authors' objective was to evaluate outcomes after implementation of an ED‐OU treatment protocol for HF exacerbation. Unblinded assessment of the effectiveness of an HF protocol was performed, controlled by outcome for 9 months prior to implementation. This included diagnostic and therapeutic algorithms, cardiology consultation, close monitoring, patient education, and discharge planning. Adverse outcomes were defined as the 90‐day rates of ED HF revisits, hospital HF readmissions, or death, as determined by chart review, computer database search, and phone follow‐up. One hundred fifty‐four patients were enrolled; 50 entered before, and 104 after protocol implementation. Only six (12%) in the preprotocol and one (1%) of the post protocol group were lost to follow‐up. After an OU visit, post protocol 90‐day ED HF revisit rates declined 56% (0.90–0.51; p<0.0000) and the 90‐day HF rehospitalization rate decreased 64% (0.77–0.50; p=0.007). The 90‐day rates of death and OU HF readmission decreased from 4% to 1% (p=0.096) and 18% to 11% (p=0.099), respectively. An intensive outpatient ED OU HF management protocol safely decreases 90‐day rates of emergency department visits and inpatient hospitalizations.
Tricuspid Stenosis: A Rare Cause of Heart Failure in the United States
Authors: Staicu Irina , Aslam Mohammad Shakil , Brookfield Leslie , Lakier Jeffrey B.
Published: June 2007

The authors describe the case of a 72‐year‐old patient who has a history of rheumatic heart disease and had mitral valve replacement in childhood. She presents with progressive right‐sided heart failure unresponsive to medical therapy. On evaluation she was found to have severe aortic stenosis and severe tricuspid stenosis. Surgical correction of both valves resulted in complete resolution of heart failure with remarkable improvement in quality of life. The symptoms, physical findings, and treatment options will be discussed.
Tackling the Devastating Effects of Heparin‐Induced Thrombocytopenia
Authors: Abraham Prasad , Uber Walter E. , Lazarchick John , Crumbley Arthur J.
Published: June 2007

Heparin‐induced thrombocytopenia with associated thrombosis is a potentially catastrophic complication of heparin therapy. Heart failure patients often require heparin therapy in the setting of multiple comorbidities, particularly renal insufficiency. The authors report a case of heparin‐induced thrombocytopenia with associated thrombosis in a patient with multisystem organ failure and discuss dosing regimens using lepirudin for the treatment of this disorder. The potential risk for excessive anticoagulation is highlighted and a conservative dosing strategy with frequent monitoring of this agent in the presence of renal failure is emphasized.
Enhanced External Counterpulsation in Patients With Heart Failure: A Multicenter Feasibility Study
Authors: Soran Ozlem , Fleishman Bruce , Demarco Theresa , Grossman William , Schneider Virginia M. , Manzo Karen , De Lame Paul‐André , Feldman Arthur M.
Published: June 2007

To assess the feasibility of using enhanced external counterpulsation to treat patients with heart failure, 26 patients with stable heart failure (New York Heart Association classes II–III), with a left ventricular ejection fraction at or below 35%, and without fluid overload, were treated with enhanced external counterpulsation (1 hour daily, 5 days a week, to a total of 35 hours). Patients were followed for 6 months after completing the course of enhanced external counterpulsation. The primary parameter was safety as reflected by adverse events or by changes in laboratory parameters. Secondary end points included changes in exercise capacity and quality of life. There were no clinically significant problems associated with the administration of enhanced external counterpulsation. Significant improvements were seen in exercise capacity (peak oxygen uptake and exercise duration), and in quality of life assessments, at 1 week and 6 months after the course of enhanced external counterpulsation. This study suggests that enhanced external counterpulsation is safe and well tolerated in patients with stable heart failure, and that a randomized, controlled study of enhanced external counterpulsation in these patients is warranted.
Metabolic and Hormonal Disturbances in Women with Epilepsy on Antiepileptic Drug Monotherapy
Authors: Kim Jee Young , Lee Hyang Woon
Published: June 2007

Summary:  Purpose: Women with epilepsy (WWE) tend to have hormonal and metabolic abnormalities, raising concerns about an increased risk of cardiovascular disorders. This study was performed to determine whether epilepsy itself and/or antiepileptic drug (AED) medication cause metabolic abnormalities.

Methods: WWE in premenopausal state aged 18 to 45 years old, currently on AED monotherapy for more than six months, were recruited for this study. The subjects checked their oral temperature each morning, and tested serum levels for lipid profiles, insulin, glucose, and leptin. A HOMA‐index was used as a marker for insulin resistance.

Results: Of the 54 total patients, 18 women were diagnosed with primary generalized epilepsy (PGE) and the other 36 were diagnosed with localization‐related epilepsy (LRE). Among the subjects, 19 women were on carbamazepine (CBZ), 12 on valproate (VPA), 12 on lamotrigine (LTG), and 11 on topiramate (TPM). Body mass index increased and HDL‐cholesterol decreased in patients on VPA monotherapy compared with CBZ, LTG, or TPM (p = 0.046 and 0.002). Metabolic syndrome was more frequently associated with VPA‐treated patients (41.7%) than CBZ (5.3%), LTG (0%), or TPM group (0%) (p = 0.005). There were no differences in hormonal and metabolic indices between PGE and LRE groups.

Conclusions: WWE on VPA monotherapy are more obese and more frequently suffer from metabolic syndrome. LTG or TPM may be safer when prescribed to the patients with high risk of cardiovascular disease.
Epilepsy Surgery in Children with Gliomatosis Cerebri
Authors: Maton Bruno , Resnick Trevor , Jayakar Prasanna , Morrison Glenn , Duchowny Michael
Published: June 2007

Summary:  Purpose: Gliomatosis cerebri (GC) is a rare neoplastic disorder that may present as intractable epilepsy during early life. We report our experience regarding the evaluation and the surgical treatment of epilepsy in this population.

Methods: All children evaluated between 1990 and 2006 for surgery of epilepsy (n = 741) with pathologically proven GC were selected.

Results: We identified four male children with age at seizure onset ranging from 4 months to 11 years. Two had hemiparesis and one child with infantile spasms was developmentally delayed. Seizures occurred daily (n = 3) or monthly (n = 1). Ictal semiology was consistent with psychomotor seizures (n = 1), partial motor seizures (n = 2), and asymmetric epileptic spasms (n = 1). Surgery was symptomatic and aimed at debulking and controlling the epilepsy. Procedure was individually tailored based on the presurgical evaluation. Brain MRI revealed widespread hemispheric involvement (n = 3) or infiltration of the temporal lobe and basal ganglia (n = 1). Two patients were initially misdiagnosed as hemispheric cortical dysplasia and hemimegalencephaly. Scalp EEG was nonlocalizing in two cases, showed a right temporal focus in one case, and was not performed in one case. Interictal SPECT in one patient revealed widespread hemispheric hypoperfusion. Three cases were resected under ECoG guidance after a mean delay of 11 months after seizure onset. Following functional hemispherectomy (n = 1) or focal cortical resection (n = 2), all children were alive and seizure free with a mean follow‐up of 48 months (2–5 years). No unexpected complication was reported. One nonoperated case was alive but still seizing after 15 months follow‐up. Chemotherapy was associated in three cases.

Conclusions: GC is a rare cause of medically resistant epilepsy that may present in early life. The lack of a discrete lesion may lead to diagnostic uncertainty, especially in infancy. Epilepsy surgery is an effective therapy that can improve quality of life.
Electroclinical Features of a Family with Simple Febrile Seizures and Temporal Lobe Epilepsy Associated with SCN1A Loss‐of‐Function Mutation
Authors: Colosimo Eleonora , Gambardella Antonio , Mantegazza Massimo , Labate Angelo , Rusconi Raffaela , Schiavon Emanuele , Annesi Ferdinanda , Cassulini Rita R. , Carrideo Sara , Chifari Rosanna , Canevini Maria Paola , Canger Raffaele , Franceschetti Silvana , Annesi Grazia , Wanke Enzo , Quattrone Aldo
Published: June 2007

Summary:  Purpose: To report in detail the electroclinical features of a large family in which we recently identified a missense mutation (M145T) of a well‐conserved amino acid in the first transmembrane segment of domain I of the human SCN1A. We showed that the mutation is associated with a loss of SCN1A function.

Methods: The family originates from southern Italy and contains 35 members spread over four generations. Of the 14 affected individuals, the 13 still living members (7 males, mean age 36.6 ± 20.4) underwent a complete electroclinical evaluation.

Results: All 13 affected family members had febrile seizures (FS) up to the age of 6 years. Age at onset of FS ranged from 5 to 45 months with a mean age of 12.8 ± 12.9 months. One of the 13 was affected by post‐traumatic epilepsy. Three of the 13 later developed temporal lobe epilepsy (TLE) with both simple focal seizures, and also very rare focal complex or nocturnal secondary generalized tonic–clonic seizures. In two of the three patients who later developed TLE, the MRI studies revealed mesial temporal sclerosis.

Conclusions: Our findings illustrate that SCN1A mutations can cause simple FS associated with TLE, which differ from the characteristic clinical spectrum of GEFS+. It is open to conjecture if this unusual phenotype might at least in part be related to the fact that M145T is the first missense mutation found in DIS1 of SCN1A.
Prevalence of Active Epilepsy and Health‐Related Quality of Life among Adults with Self‐Reported Epilepsy in California: California Health Interview Survey, 2003
Authors: Kobau Rosemarie , Zahran Hatice , Grant David , Thurman David J. , Price Patricia H. , Zack Matthew M.
Published: June 2007

Summary: Purpose:To examine the prevalence of self‐reported epilepsy and active epilepsy, associated burden of impaired health‐related quality of life, risk factors, and access to care in adults with self‐reported epilepsy, and those classified as having active epilepsy with and without recent seizures.

Methods:We analyzed data from adults aged ≥18 years (n = 41,494) who participated in the 2003 California Health Interview Survey (CHIS).

Results:In California, 1.2% of adults reported ever being told they had epilepsy or seizure disorder, and 0.7% were classified as having active epilepsy. About three‐fourths of adults with active epilepsy with recent seizures reported fair or poor health status. Adults with active epilepsy with recent seizures reported almost two weeks of poor physical or mental health and activity limitation days compared with two to 4 days per month in those without epilepsy. Among adults with active epilepsy and recent seizures, about one‐quarter reported not taking any medicine to control their seizure disorder or epilepsy. About one‐third reported physical disability/unable to work compared to a small proportion of the general population. The majority of adults with active epilepsy reported having a regular source of medical care.

Conclusion:Our findings highlight the burden of epilepsy among adults in California. CHIS serves as a model demonstrating the value of including questions about epilepsy on public health surveillance systems to ascertain the burden of the disorder and to guide intervention research and public policy to improve HRQOL in people with epilepsy.