bluuebunny/crossref_metadata_2025 huggingface dataset:
Immune Modulation Therapy in Heart Failure
Authors: Mielniczuk Lisa M. , Baughman Kenneth L.
Published: January 2007

Several lines of evidence suggest that inflammation plays a pathogenic role in the development and progression of congestive heart failure, influencing heart contractility and hypertrophy, promoting apoptosis, and contributing to the myocardial remodeling process. As the prevalence of heart failure continues to increase, novel therapeutic strategies are employed to decrease the burden of this disease. Although multiple studies have suggested a potential for immunomodulatory therapy in heart failure patients, the precise role of this targeted approach still remains to be determined. Further research is needed to identify the key factors in the immunopathogenesis of heart failure, identify the patients who are most likely to respond, and develop management strategies that result in consistent benefit leading to decreased morbidity and mortality in the heart failure patient population.
Peripheral Edema Masks the Diagnoses of P Pulmonale, P Mitrale, and Biatrial Abnormality: Clinical Implications for Patients With Heart Failure
Authors: Madias John E.
Published: January 2007

Peripheral edema (PED) impacts the size of the electrocardiogram, attenuating the amplitude and duration of QRS complexes and P waves. Diagnostic configurations of P pulmonale (Pp), P mitrale (Pm), and biatrial abnormality (Pb) are based on measurements of the amplitude and duration of the P waves. To investigate whether PED masks the diagnoses of Pp, Pm, and Pb, 15 patients (nine who suffered PED and six who did not gain weight during hospitalization, who served as controls) were studied. Of nine patients with PED, one had Pp, four had Pm, and four had Pb on admission, but such configurations were abolished after development of PED, except in one patient with Pm. Of six controls, one patient had Pp, three had Pm, and two had Pb, both on admission and at discharge. There was no difference in sex (p=0.61) or age (p=0.27) between the patients with PED and the controls; however, patients with PED were sicker and eventually died, while none of the controls did so. Electrocardiographic atrial abnormalities can be masked by PED, resulting from the attenuation of P waves and mediated by a decrease in the electrical impedance of the body's volume conductor due to water overload. These have clinical implications for patients with heart failure.
Myocardial Perfusion As Assessed by Positron Emission Tomography During Long‐Term Mechanical Circulatory Support
Authors: Letsou George V. , Sdringola Stefano , Gregoric Igor D. , Patel Vijay , Myers Timothy J. , Delgado Reynolds M. , Frazier O.H.
Published: January 2007

Although mechanical circulatory support (MCS) can improve myocardial function in patients with advanced heart failure, its effects on relative myocardial perfusion are unclear. Using positron emission tomographic imaging techniques, the authors assessed relative myocardial perfusion in patients with ischemic or idiopathic cardiomyopathy who were receiving chronic MCS with a left ventricular assist device (pulsatile HeartMate [n=2] [Thoratec Corporation, Pleasanton, CA] or nonpulsatile Jarvik 2000 [n=4] [Jarvik Heart, Inc., New York, NY]). Relative myocardial perfusion was compared at lower and higher levels of MCS (50 vs. 100–110 ejections/min for the HeartMate and 8000 vs. 12,000 rpm for the Jarvik 2000). The size and severity of perfusion defects at rest and after dipyridamole stress were measured objectively and subjectively by computer algorithms and visual inspection, respectively. Relative myocardial perfusion increased >5% from baseline in only one of six patients when MCS was increased. No change in relative myocardial perfusion of >5% was seen in any of the other five patients, even after subsequent dipyridamole stress positron emission tomographic imaging. These pilot study findings suggest that the decreased metabolic requirements induced by ventricular unloading correspondingly decreased blood flow requirements to physiologically inactive myocardium.
Acute and Chronic Oral Magnesium Supplementation: Effects on Endothelial Function, Exercise Capacity, and Quality of Life in Patients With Symptomatic Heart Failure
Authors: Fuentes Johanna C. , Salmon Adrian A. , Silver Marc A.
Published: January 2007

Endothelial dysfunction is an important pathophysiologic mechanism in the progression of heart failure. The objective of the present study was to determine the effects of acute and chronic oral magnesium supplementation on endothelial function in patients with symptomatic heart failure. Twenty‐two symptomatic chronic heart failure patients were randomized to receive 800 mg oral magnesium oxide daily or placebo for 3 months. Data collected included large and small arterial elasticity/compliance, hemodynamic parameters, exercise capacity, and quality‐of‐life score at baseline, 1 week, and 3 months. Patients who received magnesium had improved small arterial compliance at 3 months from baseline compared with placebo. This study suggests that chronic supplementation with oral magnesium is well tolerated and could improve endothelial function in symptomatic heart failure patients.
The Effect of Anemia on Mortality in Indigent Patients With Mild‐to‐Moderate Chronic Heart Failure
Authors: Hebert Kathy , Horswell Ron , Arcement Lee , Hare Joshua , Stevenson Lynne
Published: January 2007

Anemia has been described as an independent predictor of death in patients with chronic heart failure. Little is known, however, about the significance of anemia in heart failure patients with severely depressed socioeconomic backgrounds who receive comprehensive care in a heart failure management program. The impact of anemia on mortality was investigated in 410 indigent chronic heart failure patients, the majority of whom were in New York Heart Association functional class I–III and were treated with angiotensin‐converting enzyme inhibitors or angiotensin receptor blockers and β blockers at maximally tolerated doses. Anemia was present in 28% of patients. In an adjusted Cox analysis, anemia was strongly associated with mortality, but only in men: hazard ratio, 2.54; 95% confidence interval, 1.31–4.93; p=0.006. The investigators conclude that anemia in this population is common and that, for men, the relative risk increase associated with anemia is high.
Pacemaker‐Induced Mitral Regurgitation as a Cause of Refractory Congestive Heart Failure During Pacing Therapy in a Patient With Hypertrophic Obstructive Cardiomyopathy
Authors: Kataoka Hajime
Published: January 2007

This report describes a woman with hypertrophic obstructive cardiomyopathy in whom initial hemodynamic improvement by dual chamber (DDD) pacing with short atrioventricular delay was excellent, but severe mitral regurgitation developed during the subsequent follow‐up period, resulting in refractory congestive heart failure. There were two possible explanations for the origin of the complicating mitral regurgitation in this patient: pacing‐induced semiclosure of the mitral valve, or left ventricular asynchrony caused by right ventricular pacing. Heart failure in patients with hypertrophic obstructive cardiomyopathy who undergo placement of a DDD pacemaker to improve not only mitral regurgitation but also heart failure symptoms can be associated with systolic mitral regurgitation as the cause of failure in DDD pacing therapy.
Brain Natriuretic Peptide Levels and Left Ventricular Functional Recovery in a Chronic Heart Failure Population
Authors: Iyengar Srinivas , Thatipelli Mallikarjun R. , Armentano Deborah S. , Chumita Rose M. , Haas Garrie J.
Published: January 2007

Due to the poor correlation between symptoms and left ventricular (LV) ejection fraction in a chronic heart failure (HF) population, the ability to identify patients who demonstrate LV functional recovery poses a dilemma for the clinician. Serial echocardiograms are not practical in a large outpatient HF population. Plasma brain natriuretic peptide (BNP) levels have a high predictive value for excluding patients with ventricular dysfunction and therefore could serve as a marker for identifying patients who demonstrate improved LV function. To evaluate this point, the researchers obtained baseline BNP levels in 380 chronic systolic HF patients seen in an outpatient HF clinic. Each patient already had a baseline echocardiogram performed before or on entry into the clinic. Fifty patients were identified in this group as having normal BNP levels (≤100 pg/mL). Echocardiograms were then repeated in this group and compared with initial echocardiographic data obtained from a retrospective chart review. The results showed that the mean LV ejection fraction for the group was increased (p<0.001), mean LV internal dimension was decreased (p<0.001), and the number of patients with an ejection fraction >50% increased from zero to 20 (p<0.001). Thus, normal BNP levels can correlate with LV recovery and could potentially offer a cost‐effective method of assessing changes in LV function in patients with chronic HF.
Novel Therapies for Heart Failure: Focus on Anti‐Inflammatory Strategies
Authors: Ramasubbu Kumudha , Oliveira Guilherme , Torre‐Amione Guillermo
Published: January 2007

The understanding of the pathomechanisms leading to heart failure has evolved from the simplistic pump‐failure concept to the more complex syndrome involving neurohormonal and inflammatory systems. Anti‐inflammatory therapy targeting specific cytokines, however, such as tumor necrosis factor‐α, has failed to show clinical benefit. As a result, the focus has turned toward more broad‐spectrum anti‐inflammatory strategies. This review examines the various broad‐spectrum anti‐inflammatory modalities that have been used in heart failure: IV immunoglobulin administration, immune modulation therapy, immune adsorption, and plasmapheresis.
Hyponatremia and Heart Failure—Treatment Considerations
Authors: Sica Domenic A.
Published: January 2007

Hyponatremia as it occurs in the heart failure patient is a multifactorial process. The presence of hyponatremia in the heart failure patient correlates with both the severity of the disease and its ultimate outcome. The therapeutic approach to the treatment of hyponatremia in heart failure has traditionally relied on attempts to improve cardiac function while at the same time limiting fluid intake. In more select circumstances, hypertonic saline, loop diuretics, and/or lithium or demeclocycline have been used. The latter two compounds act by retarding the antidiuretic effect of vasopressin but carry with their use the risk of serious renal and/or cardiovascular side effects. Alternatively, agents that selectively block the type 2 vasopressin receptor increase free water excretion without any of the adverse consequences of other therapies. Conivaptan, lixivaptan, and tolvaptan are three such aquaretic drugs. Vasopressin receptor antagonists will redefine the treatment of heart failure‐related hyponatremia and may possibly evolve as adjunct therapies to loop diuretics in diuretic‐resistant patients.
Obese Patients Have Lower B‐Type and Atrial Natriuretic Peptide Levels Compared With Nonobese
Authors: Khush Kiran K. , Gerber Ivor L. , McKeown Barry , Marcus Gregory , Vessey Joshua , Foster Elyse , Chatterjee Kanu , Michaels Andrew D.
Published: January 2007

Obesity is a risk factor for the development of heart failure, but the causal mechanism remains unclear. Impaired production or enhanced clearance of natriuretic peptides, which regulate sodium balance and sympathetic activation, may play an important role. The authors investigated the relationship of plasma B‐type natriuretic peptide and atrial natriuretic peptide levels to body mass index in 100 patients referred for left heart catheterization. Hemodynamic and echocardiographic data were obtained for all study participants. Atrial natriuretic peptide and B‐type natriuretic peptide levels were compared in obese (body mass index ≥30 kg/m2) and nonobese (body mass index <30 kg/m2) subjects. Multivariate regression analyses were performed, adjusting for clinical and hemodynamic covariates. Obese patients had significantly lower B‐type natriuretic peptide (p=0.03) and atrial natriuretic peptide (p=0.04) levels compared with nonobese. Multivariate analysis revealed lower B‐type natriuretic peptide (p=0.095) and atrial natriuretic peptide (p=0.007) levels in obese patients while controlling for age, sex, left ventricular end‐diastolic pressure, and left ventricular ejection fraction. Low levels of circulating natriuretic peptides are thus associated with obesity and may contribute to the development of heart failure.
A Transfusion‐Related Acute Myocardial Injury
Authors: Ramana Ravi K. , Helm Robert , Moran John F. , McKiernan Thomas
Published: January 2007

It is not uncommon for patients to have adverse reactions during or after blood transfusions, as they occur in l%‐6% of all blood transfusions. Although many of the reactions are clinically insignificant, a small subset of adverse reactions can lead to serious illness and even death. The authors describe a healthy young man who exhibited an acute pulmonary injury reaction to a blood product transfusion. However, he also suffered significant myocardial insult, as documented by decreased left ventricular ejection fraction and a significant rise in cardiac biomarkers. Based on current understanding of the pathophysiologic mechanisms in transfusion‐related acute lung injury, the authors hypothesized that coronary endothelial injury may have caused microvascular ischemia or have induced acute myocarditis. Empiric treatment with steroids and a j3 blocker resulted in improved left ventricular function in our patient.
Cardiac Resynchronization Therapy: A Practical Guide for Patient Management After Device Implantation, Part II
Authors: Trupp Robin J.
Published: January 2007

This is the second of a two‐part series on strategies for optimizing the delivery of cardiac resynchronization therapy (CRT). A previous article presented strategies to optimize CRT device functioning. This article focuses on patient‐related aspects. The 2005 American College of Cardiology/American Heart Association (ACC/AHA) Guidelines for Managing Adults with Chronic Heart Failure now designate CRT as a class IA recommendation for stage C patients (QRS duration, ≥120 milliseconds; left ventricular ejection fraction, ≤35%) who remain symptomatic despite optimal medical therapy. While the evidence from prospective randomized controlled trials demonstrates consistent and concordant support for CRT in patients with symptomatic heart failure and ventricular dyssynchrony, a substantial minority of patients do not experience clinical improvement from CRT. In addition to device optimization, optimizing individual patient responses is essential. This article discusses measures for enhancing the patient's response to a CRT device.
Effect of Cardiac Resynchronization Therapy on Diastolic Dysfunction As Assessed by Transthoracic Two‐Dimensional Doppler Echocardiography
Authors: Kantharia Bharat K. , Joshi Hari P. , Dudda‐Subramanya Raghunandan
Published: January 2007

Cardiac resynchronization therapy (CRT) in patients with left ventricular systolic dysfunction and electrical dyssynchrony has been shown to improve morbidity and mortality. Improvement in diastolic dysfunction may contribute to these results. In this retrospective study, the authors assessed the effect of CRT on the E/A ratio and mitral valve deceleration time, which are commonly utilized parameters of left ventricular diastolic function. In 13 patients (aged 62±11.3 years), the E/A ratio increased from 1.17±0.58 to 1.49±0.66 (p=nonsignificant) and the mitral valve deceleration time increased from 178.48±57.71 milliseconds to 227.70±76.1 8 milliseconds (p=0.054) post‐CRT. In patients without mitral regurgitation, there was a significant increase in E/A ratio, from 1.22±0.4 to 1.86±0.47 (p=0.025), but no significant change in the mitral valve deceleration time post‐CRT was observed. These data suggest improvement in diastolic dysfunction as assessed by routine two‐dimensional echocardiography in patients who receive CRT devices.
A New Angle on the Angle of Louis
Authors: Ramana Ravi K. , Sanagala Thriveni , Lichtenberg Robert
Published: January 2007

Previous literature has stated that the center of the right atrium lies approximately 5 cm below the sternal angle regardless of body position. Our objective was to measure the distance from the Angle of Louis to various locations in the right atrium and determine whether these distances vary with patients' body habitus. The authors conducted a cross‐sectional study with 52 consecutive patients who underwent computed tomography. The Angle of Louis was measured to various right atrial anatomic locations and was correlated with patients' body habitus characteristics. There was a positive correlation between patients' weight or body mass index and the distance of the Angle of Louis to right atrial locations. Therefore, using the traditional 5 cm in an obese patient can and usually will result in an underestimation of right atrial pressure. The authors suggest that in patients with body mass index >35 kg/m2 (body surface area >2.5 m2), a jugular venous column height at the clavicle is likely to indicate significantly elevated jugular venous pressure and should be considered abnormal. Therefore, further clinical assessment and subsequent therapeutic decisions of these morbidly obese patients with abnormal jugular venous pressures should be made accordingly.
Prevalence and Clinical Implications of Anemia in Congestive Heart Failure Patients Followed at a Specialized
Authors: Elabbassi Wael , Fraser Margaret , Williams Kathryn , Cassan Denise , Haddad Haissam
Published: January 2007

The objective of this study was to assess the prevalence of anemia and to investigate its association with comorbidities and its impact on clinical outcomes in patients with heart failure. The association of predefined anemia, as well as the correlation of serum hemoglobin level as a continuous variable, with outcomes of emergency department visits, hospitalization, and mortality was investigated. There were fewer anemic patients in New York Heart Association classes I and II than in classes III and IV. Anemia was associated with higher rates of emergency department visits, hospital admissions, and all‐cause mortality. Multivariable analysis showed that anemia is independently associated with mortality. When hemoglobin level was considered as a continuous variable, the authors noted that the mortality risk correlated with hemoglobin level disappears when hemoglobin level exceeds 140 g/L. The authors conclude that anemia has strong impacts on functional class and other clinical outcomes in patients with heart failure.
What is the Optimal Angiotensin‐Converting Enzyme Inhibitor Dose in Heart Failure?
Authors: Thomas Sabu , Geltman Edward
Published: January 2007

Doses of angiotensin‐converting enzyme (ACE) inhibitors used in the landmark heart failure trials that demonstrated survival benefit are rarely reached in routine practice. The authors review the current literature regarding optimal dosing of ACE inhibitors in heart failure with specific focus on neurohormonal, functional capacity, and clinical outcomes. Neurohormonal studies have shown that lower ACE inhibitor dosing may provide inadequate suppression of the renin‐angiotensin‐aldosterone system. Higher doses of ACE inhibitors have resulted in greater increments in exercise and functional capacity. Clinically, patients on high‐dose ACE inhibitor therapy had significant reductions in all‐cause mortality or hospitalization, cardiovascular hospitalizations, and heart failure‐specific hospitalizations. There is, however, conflicting evidence, and so continued uncertainty exists regarding optimal dosing. Despite underutilization of ACE inhibitors, there is insufficient evidence to support lower doses. Likewise, limited data exist for doses higher than those used in the landmark trials. Clinicians should therefore attempt to reach target doses in heart failure whenever possible.
Increase in the QRS Duration After Amelioration of Peripheral Edema and After Hemodialysis
Authors: Madias John E.
Published: January 2007

Association among weights, amplitude of QRS complexes, and QRS duration in patients with peripheral edema has been described. This study explored whether increase in QRS duration occurs with amelioration of peripheral edema or after hemodialysis. Sums of the amplitudes of the 12 electrocardiographic leads and corresponding QRS duration were measured in 12 patients with peripheral edema before and after loss of weight, in 28 patients with a critical illness but without change in their weight (“controls”), and in 1 patient before and after hemodialysis. QRS duration increased from 90.1±25.0 milliseconds to 101.7±25.8 milliseconds (P=.001) in patients with peripheral edema, was unchanged in the controls, and increased from 87.8±5.9 milliseconds before to 92.7±6.7 milliseconds after hemodialysis (P=.007). It is proposed that these increases in QRS duration are only apparent (not electrophysiologically real), representing an extracardiac phenomenon mediated by alterations in the composite impedance of the passive body volume conductor, resulting in measurement of augmented QRS complexes after fluid removal. The clinical implications for patients with congestive heart failure are discussed.
Managing Congestive Heart Failure Patient Factors in the Device Era
Authors: Sears Samuel F. , Stutts Lauren A. , Aranda Juan M. , Handberg Eileen M. , Conti Jamie B.
Published: January 2007

Device‐based care such as implantable cardioverter‐defibrillators and cardiac resynchronization therapy extends congestive heart failure (CHF) care into a new era. The purpose of this paper is 2‐fold: (1) to review the development of device‐based CHF management and the implications from a medical and patient management perspective, and (2) to provide assessment and treatment approaches on how to clinically manage patient outcomes optimally. Quality of life, depression, and anxiety are targeted as concerns for patients with CHF and cardiac resynchronization therapy/implantable cardioverter‐defibrillators. Brief clinic‐based interview questions and formal assessment tools are reviewed. Furthermore, a cognitive‐behavioral paradigm using the “Appropriate Education, Behavioral Support, and Cognitive Coping” (ABC) model is proposed to aid health care professionals in addressing patients' device‐specific concerns. Available research suggests the need for future studies assessing the efficacy of cognitive‐behavioral treatments in patients with CHF and cardiac resynchronization therapy/implantable cardioverter‐defibrillators.
The Cardio‐Renal‐Anemia Syndrome in Elderly Subjects With Heart Failure and a Normal Ejection Fraction: A Comparison With Heart Failure and Low Ejection Fraction
Authors: Cohen Rose S. , Mubashir Asyia , Wajahat Raja , Mani Susan , Hummel Scott , Maurer Mathew S.
Published: January 2007

The prevalence and severity of anemia and renal dysfunction in heart failure patients with a normal ejection fraction (HFNEF) is uncharacterized. Two hundred eighty‐five consecutive patients admitted to a community hospital with heart failure were stratified by the presence or absence of anemia and a normal or reduced ejection fraction. Comparisons of clinical variables were performed. In this sample, 62% of subjects were anemic, with no difference between those with a normal and a reduced ejection fraction (63% vs. 61%). Anemic HFNEF subjects had a lower glomerular filtration rate (37±21 mL/min vs. 52±35 mL/min; p<0.05) and more severe self‐reported symptom scores than nonanemic HFNEF subjects. Multivariate analysis confirmed the association of renal dysfunction and anemia. The authors conclude that the degree and magnitude of anemia in elderly inpatients with heart failure does not differ by ejection fraction. Worse symptoms and more severe renal dysfunction were seen in HFNEF subjects with anemia than in HFNEF subjects without anemia.
Optimizing Treatment and Outcomes in Acute Heart Failure: Beyond Initial Triage
Authors: Silver Marc A. , Peacock W. Franklin , Diercks Deborah B.
Published: January 2007

Heart failure contributes substantially to health care costs in the United States due to its prevalence and frequent necessity for repeat hospitalizations to manage episodes of acute decompensation. Heart failure overwhelmingly impacts Medicare costs, as the highest proportion of heart failure patients are older than 65 years of age. Efforts to reduce morbidity, mortality, and health care resource utilization have been achieved successfully through emergency department‐based heart failure observation units. For select patients, the observation unit can provide care with effective oral agents, including angiotensinconverting enzyme inhibitors, β‐adrenergic receptor blockers, and diuretics, as well as administration of other vasoactive agents, followed by a discharge plan of effective heart failure education and rigorous follow‐up management. As advanced pharmacologic and diagnostic therapies continue to emerge, the observation unit staff can play an integral role in the critical education and self‐management tools that are needed by the patient to ultimately improve outcomes and quality of life.
Prognosis and Mechanism of Death in Treated Heart Failure: Data From the Placebo Arm of Val‐HeFT
Authors: Cohn Jay N. , Carson Peter E. , O'Connor Christopher , Opasich Cristina , Piña Ileana L. , Scherillo Marino , Sinagra Gianfranco , Warner‐Stevenson Lynne , Tristani Felix E. , Volpi Alberto
Published: January 2007

The magnitude of benefit on mortality of combined angiotensin‐converting enzyme inhibitor (ACEI) and β‐blocker (BB) therapy for heart failure cannot be reliably assessed from prospective randomized trials of individual drugs with intent‐to‐treat analysis. The placebo arm of the Valsartan Heart Failure Trial (Val‐HeFT) included patients who remained on background therapy with ACEIs, BBs, neither, or both. The outcomes in these four subgroups should provide a better guide to mortality benefit. Overall mortality (mean follow‐up, 23 months) was 31.6% in those receiving neither neurohormonal blocker, 29% and 39% lower in those on ACEIs or BBs, respectively, and 62% lower (11.9% mortality) in those receiving both drugs. In the neither neurohormonal inhibitor group, 48% of the heart failure‐related deaths were adjudicated as sudden, whereas in the group receiving ACEIs and BBs, 79% of the deaths were sudden, and pump failure mortality was only 1% per year. The combination of ACEIs and BBs exerts a greater mortality reduction than suggested from clinical trials and reduces pump failure mortality to 1% per year.
Brain Natriuretic Peptide Levels and Response to Cardiac Resynchronization Therapy in Heart Failure Patients
Authors: Delgado Reynolds M. , Palanichamy Nanthini , Radovancevic Rajko , Vrtotec Bojan , Radovancevic Branislav
Published: January 2007

The authors used brain natriuretic peptide (BNP) as a reliable marker to identify nonresponders to cardiac resynchronization therapy (CRT) in patients with advanced heart failure. The study included 70 patients with left ventricular dysfunction (mean ejection fraction, 21±4%) and left bundle branch block (QRS duration, 164±25 milliseconds) treated with CRT. The authors reviewed data on New York Heart Association functional class, baseline ejection fraction, sodium, creatinine, QRS duration, and BNP levels 3 months before and after CRT therapy. The authors compared results of 42 patients who survived (973+192 days) after CRT implantation (responders) to those of 28 patients (nonresponders) who either expired (n=21) or underwent heart transplantation (n=5) or left ventricular assist device implantation (n=2) after an average of 371+220 days. Mean BNP levels after 3 months of CRT decreased in responders from 758±611 pg/mLto 479±451 pg/mL (P=.044), while in nonresponders there was increase in BNP levels from 1191 ±466 pg/mL to 1611 ±1583; P=.046. A rise in BNP levels was associated with poor response (death or need for transplantation or left ventricular assist device and impaired long‐term outcome), which makes it a good predictor to identify such patients.
Beta‐Blocker Therapy for Heart Failure: Should the Therapeutic Target Be Dose or Heart Rate Reduction?
Authors: Huang Robert L. , Listerman Jennifer , Goring Joann , Giesberg Carrie , Nading Mary Alice , Butler Javed
Published: January 2007

Therapeutic target with β blockers in heart failure, i.e., target heart rate reduction or β‐blocker dose, is controversial. To resolve this controversy, the authors studied 152 heart failure patients on β blockers who were divided into four groups based on median peak exercise heart rate reduction as compared with predicted and prescription of at least 50% recommended β‐blocker dose. Event‐free survival (vs. death or assist device placement or urgent transplantation) was compared. Baseline and peak exercise heart rates were 74±14 and 116±21 bpm, respectively. Median heart rate reduction at peak exercise was 35%. When median or higher peak heart rate reduction was achieved, there were no significant survival differences noted between patients on different β‐blocker doses. With below‐median peak heart rate reduction, there was a strong trend toward better event‐free survival with higher β‐blocker doses. In conclusion, the results suggest that higher heart rate reduction is associated with better outcomes for heart failure patients overall and, for patients with persistently elevated heart rates, higher β‐blocker doses provided additional benefit.
Randomized, Double‐Blind Comparison of Acute β1‐Blockade With 50 mg Metoprolol Tartrate vs 25 mg Carvedilol in Normal Subjects
Authors: Billeh Rana , Hirsh David , Barker Colin , Jorgensen Birgit , Jeger Raban , Ramanathan Krishnan , Tseng Chi‐Hong , Hudaihed Alhakam , Haas Francois , Jorde Ulrich P.
Published: January 2007

Differential efficacy of immediate‐release metoprolol tartrate and carvedilol in the treatment of congestive heart failure remains a subject of ongoing debate. The degree of β‐blockade can be assessed by percentage reduction of exercise heart rate. Twelve healthy subjects underwent symptom‐limited cardiopulmonary exercise testing repeated weekly and 2 hours after randomized, double‐blind administration of 50 mg metoprolol tartrate vs 25 mg carvedilol. Baseline heart rate, heart rate at 40% and 70% peak O2 consumption, and maximal exercise were significantly blunted more by metoprolol tartrate than by carvedilol (P<.05 for all). Peak O2 consumption was significantly reduced by metoprolol tartrate (P<.03) but not by carvedilol (P=.054). The change in O2 consumption was significantly correlated with the degree of β‐blockade (r=0.45; P<.05). In healthy subjects, a higher degree of β‐blockade is achieved with 50 mg metoprolol tartrate compared with 25 mg carvedilol.
Racial Differences in Potassium Response to Spironolactone in Heart Failure
Authors: Cavallari Larisa H. , Groo Vicki L. , Momary Kathryn M. , Fontana Deidra , Viana Marlos A.G. , Vaitkus Paul
Published: January 2007

Evidence of racial differences in aldosterone concentrations and K+ disposition suggests that response to aldosterone antagonism might vary by race. The authors sought to determine whether K+ response to spironolactone differs between African Americans and Caucasians with heart failure. Heart failure patients of African‐American (n=34) or Caucasian (n=17) race were started on spironolactone 12.5 mg/d, with up‐titration as tolerated. Laboratory values and drug therapy were similar between racial groups at baseline. Spironolactone was titrated to a median dose of 25 mg/d in both groups. Neither concomitant medications nor serum creatinine changed significantly in either group during spironolactone dose titration. Median serum K+ concentrations increased by 0.5 mEq/L (range, −0.7 to 1.6 mEq/L) in Caucasians, but only 0.1 mEq/L (range, −0.8 to 0.9 mEq/L) in African Americans; p<0.01. These data suggest that African Americans with heart failure may be less responsive to the renal effects of spironolactone.
ECG Changes in Response to Diuresis in an Ambulatory Patient With Congestive Heart Failure
Authors: Madias John E.
Published: January 2007

This case report describes an ambulatory patient with congestive heart failure and peripheral edema who lost 18 Ib in response to enhanced diuresis over the course of 1 week. The ECG showed increases in the amplitude of P waves, QRS complexes, and T waves; the duration of P waves, QRS complexes, and QT intervals; and the dispersion of P and QT. The clinical implications of these ECG changes are discussed.
Epicardial Left Ventricular Lead Placement for Cardiac Resynchronization Therapy Following Failed Coronary Sinus Approach
Authors: Shah Ravi V. , Lewis Eldrin F. , Givertz Michael M.
Published: January 2007

Outcomes of surgical left ventricular (LV) lead placement in patients with failing percutaneous cardiac resynchronization therapy (CRT) are not well defined. The authors reviewed all primary epicardial LV lead placements at their institution to identify patient population, perioperative course, and structural and functional outcomes, and compared this group with patients who had successful percutaneous CRT. Fourteen patients (11%) required epicardial LV lead placement via left thoracotomy or thoracoscopy with mean intensive care unit stay of 2.1 days and inotrope use in 38%. Complications included ventricular fibrillatory arrest, stroke, hypotension, and major bleeding, but there was no difference in 90‐day survival between epicardial and percutaneous CRT lead placement. In survivors, New York Heart Association class improved from 3.0 to 2.3 (P=.008) without a change in ejection fraction or severity of mitral regurgitation. Thus, in patients with unsuccessful percutaneous CRT, epicardial LV lead placement is associated with perioperative morbidity, but with subsequent improvement in functional status without excess mortality.
Inflammatory Biomarkers in Heart Failure
Authors: Petersen John W. , Felker G. Michael
Published: January 2007

Multiple lines of evidence support the “cytokine hypothesis,” which suggests that inflammation plays an important role in the development and progression of heart failure. Circulating markers of inflammation, such as tumor necrosis factor α, interleukin 6, and C‐reactive protein, may be useful in establishing the diagnosis, gauging prognosis, and evaluating the response to therapy in patients with heart failure. In addition to their potential as heart failure biomarkers, inflammatory cytokines have been investigated as targets of heart failure therapy. Although results for therapies directed against specific cytokines (such as tumor necrosis factor α) have thus far been disappointing, multiple studies continue to address the therapeutic potential of modulating the immune response in heart failure. In this review, the authors analyze available data supporting the use of inflammatory markers both as biomarkers and as potential therapeutic targets.
Validation and Clinical Utility of a Simple In‐Home Testing Tool for Sleep‐Disordered Breathing and Arrhythmias in Heart Failure: Results of the Sleep Events, Arrhythmias, and Respiratory Analysis in Congestive Heart Failure (SEARCH) Study
Authors: Abraham William T. , Trupp Robin J. , Phillips Barbara , Bourge Robert C. , Bailey Brian , Harding Susan M. , Schofield Peter , Pilsworth Samantha , Shneerson John M. , Di Salvo Thomas , Camuso Janice , Johnson Douglas , King Martin , Javaheri Shahrokh
Published: January 2007

Fifty patients with New York Heart Association class III systolic heart failure were enrolled in this prospective multicenter study that compared the diagnostic accuracy of a home‐based cardiorespiratory testing system with standard attended polysomnography. Patients underwent at least 2 nights of evaluation and were scored by blinded observers. At diagnostic cutoff points of ≥5, ≥10, and ≥15 events per hour for respiratory disturbance severity, polysomnography demonstrated a sleep‐disordered breathing prevalence of 69%, 59%, and 49%, respectively. Compared with polysomnography, the cardiorespiratory testing system demonstrated predictive accuracies of 73%, 73%, and 75%, which improved to 87%, 87%, and 83%, respectively, when analysis of covariance suggested reanalysis omitting one site's data. The system accurately identified both suspected and unsuspected arrhythmias. The device was judged by 80% of patients to be easy or very easy to use, and 74% of patients expressed a preference for the in‐home system. Therefore, this system represents a reasonable home testing device in these patients.
The Effect of Administering Erythropoiesis‐Stimulating Proteins in Patients With Chronic Heart Failure: Results From a Retrospective Study
Authors: Delgado Reynolds M. , Radovancevic Rajko , van Rossem Charles C. , Gaemers Sebastiaan J.M. , Castanes Stratego , Adams Stephen C. , Bracey Arthur W. , Radovancevic Branislav
Published: January 2007

Anemia is prevalent in patients with chronic heart failure and is associated with worse symptoms and poor prognosis. The authors reviewed the charts of all patients (N=467) treated at Texas Heart Institute from January 2000 to October 2003, during which time a clinical protocol offered treatment with erythropoiesis‐stimulating proteins. Post‐treatment, the authors observed a significant increase in mean ± SD hemoglobin, from 9.9±1.1 g/dL to 11.7±1.5 g/dL (P<.0001), improvement of renal function (a decrease in mean levels of creatinine and blood urea nitrogen), and fewer hospital admissions (1.0±1.4 vs 1.8±1.6; P=.0003) without an increase in adverse clinical events, compared with pretreatment and compared with an untreated control group. These results suggest a potential benefit of anemia treatment with recombinant erythropoiesis‐stimulating proteins in patients with chronic heart failure.
Genetics in Heart Failure: Where Are We Headed?
Authors: de Boer Rudolf A. , van den Berg Maarten P. , van Veldhuisen Dirk J.
Published: January 2007

Heart failure is a complex disease with many precipitating factors. Novel insights into the genetic background of heart failure have boosted new areas of research that gave rise to the concept of genetic predisposition for heart failure. Various genetic defects and variances have been identified and subsequently linked to the onset of or progression to heart failure. Nevertheless, our understanding of the genetic basis for heart failure is incomplete because we lack knowledge of the functionality of genetic variances. We also do not understand the impact of genetic variances in noncoding DNA because of logistic problems in performing whole‐genome scans and difficulties in statistical evaluation of large amounts of data generated by the genetic boom. It is expected that in the future we will be able to overcome these problems and apply the knowledge gained by genetic analyses to target and optimize treatment.
Angiotensin‐Converting Enzyme Inhibition—Emerging Pulmonary Issues Relating to Cough
Authors: Sica Domenic A. , Brath Lisa
Published: January 2007

Angiotensin‐converting enzyme (ACE) inhibitors are viewed by many as important treatment options for both the management of hypertension and the provision of end‐organ protection. ACE inhibitors have not been looked on as having any clearly recognizable direct pulmonary benefits; rather, their pulmonary effects have been felt to be a nuisance by virtue of their association with cough. ACE inhibitor‐related cough is well characterized. What is less well appreciated is the relationship between sleep apnea, pneumonia, and ACE inhibitor‐related cough. These new pulmonary observations in patients afflicted with an ACE inhibitor‐related cough should revive interest in this bothersome side effect
Improving the Accuracy of Impedance Cardiac Output in the Intensive Care Unit: Comparison With Thermodilution Cardiac Output
Authors: Fuller Hugh D.
Published: January 2007

This study examined the effect of impedance algorithm adjustment to reflect abnormalities found in cardiac output estimation in the intensive care unit. Impedance (Kubicek and Sramek equations) and thermodilution were measured concurrently in 61 patients. The mean difference between Kubicek and thermodilution (n=40) was 1.47 L/min (95% confidence interval [CI], 0.47–2.47) and between Sramek and thermodilution (n=54) was 2.68 L/min (95% CI, 1.93–3.44). Exclusion of patients with valve regurgitation improved agreement between Kubicek and thermodilution (n=32), with a mean difference of 2.02 L/min (95% CI, 1.10–2.94). Multiple regression determined the role of skinfold thickness, pH, hematocrit, sodium, chloride, albumin, protein, and urea within impedance. Kubicek was recalculated using the new algorithm and recompared with thermodilution. The mean difference was −0.38 L/min (95% CI, −1.92 to 1.16). This study found poor agreement between impedance and thermodilution in critically ill patients, but exclusion of those with valve regurgitation and adjustment for hematocrit and skinfold thickness improved agreement.
Heart Failure in Community Practice: Relationship to Age and Sex in a β‐Blocker Registry
Authors: Franciosa Joseph A. , Nelson Jeanenne J. , Lukas Mary Ann , Lottes Sandra R. , Massie Barry M. , Fowler Michael B. , Greenberg Barry , Gilbert Edward M. , Abraham William T.
Published: January 2007

Women and the elderly are underrepresented in clinical trials of heart failure (HF). The authors analyzed, by sex and age groups, a registry of 4280 community patients initiating carvedilol for HF. Women (n=1485) were older than men (n=2793) and had worse functional class with higher left ventricular ejection fraction and blood pressure. Women also had more HF hospitalizations, less use of angiotensin‐converting enzyme inhibitors, and lower doses of carvedilol. Nevertheless, during 1‐year follow‐up, both groups experienced greater than 40% reductions in HF hospitalizations (P<.001), with mortality of 7.3% in women vs 9.1% in men (P=.085). With increasing age, left ventricular ejection fraction, blood pressure, and functional class increased, whereas angiotensin‐converting enzyme inhibitor use and carvedilol doses decreased. HF hospitalizations fell at least 40% in all age groups after starting carvedilol (P<.001). Characteristics of women and the elderly with HF in the community suggest increased risk, but both populations respond well after initiating carvedilol.
Enhanced External Counterpulsation Improves Exercise Duration and Peak Oxygen Consumption in Older Patients With Heart Failure: A Subgroup Analysis of the PEECH Trial
Authors: Abbottsmith Charles W. , Chung Eugene S. , Varricchione Thomas , Varricchione Thomas , de Lame Paul‐Andre , Silver Marc A. , Francis Gary S. , Feldman Arthur M. ,   for the Prospective Evaluation of EECP in Congestive Heart Failure (PEECH) Investigators
Published: January 2007

The Prospective Evaluation of Enhanced External Counterpulsation in Congestive Heart Failure (PEECH) trial demonstrated that enhanced external counterpulsation (EECP) therapy increased exercise duration and improved functional status and quality of life without affecting peak oxygen consumption. The authors present data from a prespecified subgroup of elderly patients (65 years or older) enrolled in the PEECH trial. The 2 co‐primary end points were the percentage of subjects with a >60‐second increase in exercise duration and the percentage of subjects with a >1.25‐mL/kg/min increase in peak volume of oxygen consumption. At 6‐month follow‐up, the exercise responder rate was significantly higher in EECP patients compared with controls (P=.008). Further, in contrast to the overall PEECH study, the EECP group demonstrated a significantly higher responder rate for peak oxygen consumption (P=.017). The authors conclude that an older subgroup of PEECH subjects confirms the beneficial effect of EECP in patients with chronic, stable, mild‐to‐moderate heart failure.
Percutaneous Continuous Aortic Flow Augmentation for Cardiac Recovery in a Chronic Heart Failure Patient With Peripheral Vascular Disease
Authors: Saberin Amir , Mueller Bettina , Konstam Marvin A. , Wagner Daniel R.
Published: January 2007

Peripheral vascular disease is an obstacle to the use of continuous aortic flow augmentation (CAFA). The authors used CAFA in a patient with a 50% stenosis of the left iliac artery. Five hours after initiating therapy, flow rates dropped from 1.47 L/min to 0.2 L/min, possibly due to obstruction around the inflow cannula near the site of the iliac artery stenosis. Flow was stabilized by adequate fluid infusion and successfully restored by slightly withdrawing the tip of the inflow catheter. This finding suggests that peripheral vascular disease is a relative—not an absolute—contraindication for CAFA, but requires close monitoring of flow during CAFA therapy.
Epilepsy and Cognition
Authors: Hermann Bruce , Seidenberg Michael
Published: January 2007

It is well known that neuropsychological impairment can be associated with chronic epilepsy. This review suggests that a broad lifespan perspective of cognition in epilepsy should include consideration of: a) neurobiological factors that antedate the first seizure and influence cognition, b) epilepsy-related factors that influence brain growth and cognitive development after epilepsy is diagnosed and treated, c) clinical epilepsy and other risk factors associated with poor cognitive prognosis in the context of chronic pharmacoresistant epilepsy, and d) the modifiable and non-modifiable risk factors that influence cognitive aging in the general population.
Are Ictal Fast Ripples an “Electronic Signature” for the Seizure-onset Zone?
Authors: Miller John W.
Published: January 2007

High-Frequency Oscillations during Human Focal Seizures. Jirsch JD, Urrestarazu E, LeVan P, Olivier A, Dubeau F, Gotman J. Brain 2006;129(Pt 6):1593–1608. Discrete high-frequency oscillations (HFOs) in the range of 100–500 Hz have previously been recorded in human epileptic brains using depth microelectrodes. We describe, for the first time, similar oscillations in a cohort of unselected focal epileptic patients implanted with EEG macroelectrodes. Spectral analysis and visual inspection techniques were used to study seizures from 10 consecutive patients undergoing presurgical evaluation for medically refractory focal epilepsy. Four of these patients had focal seizure onset in the mesial temporal lobe, and in all 12 of their seizures, well-localized, segmental, very high frequency band (VHF 250–500 Hz) oscillations were visually identified near the time of seizure onset from contacts in this zone. Increased high-frequency band (HF 100–200 Hz) activity compared with the background was distinguished both visually and with spectral analysis later in the seizures of 3/4 mesial temporal patients, involving contacts in the generator region and, in one patient, areas of contralateral perihippocampal propagation. Three patients with well-defined neocortical seizure-onset areas also demonstrated focal HF or VHF oscillations confined to the seizure-onset channels during their eight seizures. No discrete HF or VHF activity was present in the poorly localized seizures from the remaining three patients. These results show that discrete HFOs can be recorded from human focal epileptic brain using depth macroelectrodes, and that they occur mostly in regions of primary epileptogenesis and rarely in regions of secondary spread. Absent high-frequency activity seems to indicate poor localization, whereas the presence of focal HFOs near the time of seizure onset may signify proximity to the epileptogenic focus in mesial temporal lobe and neocortical seizures. We postulate that focal HFOs recorded with depth macroelectrodes reflect the partial synchronization of very local oscillations such as those previously studied using microelectrodes, and result from interconnected small neuronal ensembles. Our finding that localized HFOs occur in varying anatomical structures and pathological conditions perhaps indicates commonality to diverse epileptogenic etiologies.