bluuebunny/crossref_metadata_2025 huggingface dataset:
Control of Heart Rate Versus Rhythm in Rheumatic Atrial Fibrillation: A Randomized Study
Authors: Vora Amit , Karnad Dilip , Goyal Venkat , Naik Ajay , Gupta Anup , Lokhandwala Yas , Kulkarni Hema , Singh Bramah N.
Published: March 2006

Background: Patients with rheumatic heart disease with atrial fibrillation incur significant morbidity and mortality. Which approach, ventricular rate control or maintenance of sinus rhythm, in this setting might be superior is not known. The role of amiodarone in this patient population for maintaining sinus rhythm has not been evaluated.

Methods and Results: We prospectively studied 144 patients with chronic rheumatic atrial fibrillation in a double-blind protocol in which rhythm control (group I), comprising 48 patients each with amiodarone (group Ia) and placebo (group Ib), were compared with each other and with patients in a ventricular rate control group (group II) in which the effects by diltiazem were determined (n = 48, open-label). Direct current cardioversion was attempted in group I. The mean age of the study population was 38.6 ± 10.3 years, left atrial size, 4.7 ±0.6 cm; atrial fibrillation duration, 6.1 ± 5.4 years; and 72.9% had valvular interventions performed. At 1 year, 45 patients with sinus rhythm in group I compared with 48 in group II demonstrated an increase in exercise time (2.6 ± 1.9 vs. 0.6 ± 2.5 min, P = .001), improvement in New York Heart Association class of 1 or more ( P = .002), and improvement in the quality-of-life score of one or greater ( P = 0.01) with no difference in hospitalizations, systemic bleeds, or thromboembolism. Five patients died in group II; none died in group I ( P =.02). In group I, 73 of 87 (83.9%) patients converted to sinus rhythm and 45 of 86 (52.3%) patients maintained the rhythm at 1 year. Conversion rates were 38 of 43 (88.4%) with amiodarone versus 34 of 44 (77.3%) with placebo ( P = .49); the corresponding rate for maintaining sinus rhythm was 29 of 42 (69.1%) versus 16 of 44 (36.4%) ( P = .008). A larger number of electrical cardioversions were required in the placebo group (2.1 vs. 1.4, P = .011).

Conclusions: Maintenance of sinus rhythm is superior to ventricular rate control in patients with rheumatic atrial fibrillation with respect to effects on exercise capacity, quality of life, morbidity, and possibly mortality. Sinus rhythm could be restored in most patients, and amiodarone was superior to placebo in the restoration and maintenance of sinus rhythm.
Continuous Light Exposure and Sympathectomy Suppress Circadian Rhythm of Blood Pressure in Rats
Authors: Briaud S. A. , Zhang B. L. , Sannajust F.
Published: March 2006

Background: Although the 24-hour rhythm in blood pressure is well known, it is not clear how environmental light controls circadian cardiovascular and behavioral rhythms.

Methods and Results: The prolonged exposure of Wistar rats to continuous light for 17 weeks, beginning at 5 weeks old, induced a complete suppression of their blood pressure, heart rate, spontaneous locomotor activity, and body temperature circadian rhythms. Daily subcutaneous melatonin injections at the theoretical onset of darkness for 21 days could not restore light-suppressed blood pressure circadian rhythm, whereas it partially synchronized heart rate and body temperature rhythms and it fully restored spontaneous locomotor activity rhythms, as measured by radiotelemetry. The transfer of these rats from constant light to a standard 12:12-hour light/dark photoperiod fully restored circadian rhythmicity within 2 to 5 days, although their 24-hour diastolic blood pressure remained elevated. Synchronized rats were then subjected to superior cervical ganglionectomy (SCGx) and 6-hydroxydopamine sympathectomy (SYMPx). SCGx plus SYMPx completely abolished the circadian rhythm in blood pressure and significantly reduced those in heart rate, spontaneous locomotor activity, and body temperature.

Conclusions: We conclude that in Wistar rats exposed to continuous light, the light-induced increase in sympathetic outflow can suppress blood pressure circadian rhythm, and sustained cardiac wall stress can alter diastolic function at rest. Preserved inotropy in these conditions must result from an adaptative hypertrophic response of myocytes.
Pharmacodynamics ofβ-Blockers in Heart Failure: Lessons from the Carvedilol Or Metoprolol European Trial
Authors: Bauman Jerry L. , Talbert Robert L.
Published: March 2006

Heart failure is a growing public health problem in the United States, and the approach to the treatment of heart failure has undergone a radical transformation in the past decade. The use of β-blocker therapy in heart failure patients is now widely recommended, based on evidence from large-scale clinical trials demonstrating that bisoprolol, carvedilol, and extended-release metoprolol succinate significantly reduce morbidity and mortality in patients with heart failure. Although these agents appear to provide similar benefits, the question remains whether pharmacologic differences among them could translate to differences in clinical outcomes. The Carvedilol Or Metoprolol European Trial (COMET) compared nonselective blockade of the β1-/β2-/α1-adrenergic receptors with carvedilol versus selective β1-blockade with immediate-release metoprolol tartrate in patients with chronic heart failure. The trial found that carvedilol significantly reduced all-cause mortality compared with immediate-release metoprolol tartrate, although there were no differences in hospitalizations. Herein we review the pharmacokinetics and pharmacodynamics of metoprolol and carvedilol. In doing so, several issues regarding the design of COMET are identified that could alter the interpretation of the results of this trial. These include the choice of dose and dosage regimen of immediate-release metoprolol tartrate, a dosage form that has never been shown to reduce mortality in patients with heart failure. Additional studies are needed to fully understand whether there are any advantages of selective versus nonselective adrenergic blockade and whether there are any clinically meaningful differences in effectiveness between β-blockers with proven benefit in the management of chronic heart failure. The results of COMET demonstrate that all β-blockers and dosage forms are not interchangeable when prescribed for heart failure. Clinicians should choose only those agents (and dosage forms) that have been proven to reduce mortality in this patient population.
Sinus Node Dysfunction Secondary to Hyperparathyroidism
Authors: Shah Atman P. , Lopez Angela , Wachsner Robin Y. , Meymandi Sheba K. , El-Bialy Adel K. , Ichiuji Anne M.
Published: March 2006

We present two patients who were diagnosed with symptomatic sinus node dysfunction in the setting of hypercalcemia secondary to hyperparathyroidism. An extensive review of the literature has not revealed previous reports of this pathologic process.
Intravenous Nicorandil Can Reduce QT Dispersion and Prevent Bradyarrhythmia During Percutaneous Transluminal Coronary Angioplasty of the Right Coronary Artery
Authors: Ueda Hiroyasu , Hayashi Tomoshige , Tsumura Kei , Yoshimaru Kiyomichi , Nakayama Yasunori , Yoshikawa Junichi
Published: March 2006

Background: Nicorandil, a potassium channel opener, is used for the treatment of angina pectoris and has a pharmacologic preconditioning effect. This study evaluated whether intravenous nicorandil reduces QT dispersion and prevents bradyarrhythmia during percutaneous transluminal coronary angioplasty (PTCA) of the right coronary artery.

Methods: A historical cohort study on the effect of nicorandil on QT dispersion and bradyarrhythmia was conducted. Fifty patients who underwent PTCA of the right coronary artery were enrolled. The patients were divided into a nicorandil (n = 25) group and control group (n = 25). Nicorandil was injected at 4 mg/h continuously 1 hour before PTCA in the nicorandil group. QT dispersion was measured at 1 hour before PTCA (baseline), immediately before PTCA, and 1 minute after the initiation of the first balloon inflation.

Results: QT dispersion at 1 minute after the initiation of the first balloon inflation in the control group increased significantly (QT dispersion: 37.1 ± 17.8 msec and 21.7 ± 12.2 msec, respectively, P < .001 vs baseline in the control group), and this was larger than at 1 minute after the initiation of the first balloon inflation in the nicorandil group (QT dispersion: 37.1 ± 17.8 msec and 20.8 ± 9.4 msec, respectively, P < .001). By two-way repeated measures analysis of variance, there were significant interactions between the time factor and the grouping factor in QT dispersion ( P < .001). Bradyarrhythmia was observed in 6 patients in the control group, but none was observed in the nicorandil group.

Conclusions: Intravenous nicorandil reduces QT dispersion and prevents bradyarrhythmia during PTCA of the right coronary artery.
Effects of Low-Dose Atorvastatin on Vascular Responses in Patients Undergoing Percutaneous Coronary Intervention With Stenting
Authors: Bae Jang-Ho , Bassenge Eberhard , Kim Ki-Young , Synn Yi-Chul , Park ki-Rack , Schwemmer Michael
Published: March 2006

Background: The primary endpoint of this study was to evaluate the effects of low-dose atorvastatin on carotid intima-media thickness (IMT) and endothelial function, and the secondary endpoint comprised restenosis and target lesion revascularization (TLR) in patients undergoing percutaneous coronary intervention (PCI) with stenting for the treatment of coronary artery disease.

Methods: Two hundred five consecutive patients (mean age, 60 years) undergoing PCI were prospectively randomized to usual therapy (control group, n = 100) or to 10 mg of atorvastatin daily plus usual therapy (statin group, n = 105). Carotid IMT, endothelial function (flow-mediated dilatation [FMD] of the brachial artery), and coronary angiograms were taken before the study and 6 months after randomization. The 6-month follow-up measurements of the above factors were obtained in 83 patients (83%) of the control group and in 97 patients (92%) of the statin group.

Results: No significant differences were noted in the baseline clinical and angiographic findings in either group. FMD was significantly improved during the 6 months in the statin group (4.38% ± 1.7% vs 4.85% ± 1.6%, P = .003), but did not change in the control group. Carotid IMT did not show any significant changes at 6 months in either group. There was a trend in favor of statin in terms of restenosis rate (26.8% vs 36.1%, P = .177) and TLR rate (18.6% vs 25.3%, P = .274). The changes of FMD were significantly correlated with the changes of total cholesterol and the changes of low-density lipoprotein, respectively ( r= -0.336, P = .009, and r = -0.310, P = .046).

Conclusion: Low-dose atorvastatin reduces endothelial dysfunction as measured by FMD, which coincides with the beneficial effects on lipid profiles, and can decrease restenosis and TLR rate in patients undergoing PCI with stenting.
Effect of Potassium-Channel Opener Therapy on Reperfused Infarction in Hypertrophied Hearts: Demonstration of Preconditioning by Using Functional and Contrast-Enhanced Magnetic Resonance Imaging
Authors: Schalla Simon , Higgins Charles B. , Chujo Mitsuaki , Saeed Maythem
Published: March 2006

Effects of therapy with the potassium-channel opener and vasodilator nicorandil were studied in reperfused infarction of hypertrophied hearts by using magnetic resonance imaging (MRI), hemodynamic measurements, and histochemical staining. Aortic banding was performed on 22 Sprague-Dawley rats to induce left ventricular (LV) hypertrophy; 11 were the controls. Eight weeks later, the left coronary artery was occluded for 25 minutes in all 33 animals, followed by 3 hours of reperfusion. During occlusion, 11 rats with LV hypertrophy received nicorandil (0.1 mg/kg bolus and 1.5 mg/kg/h for 3 hours). The new necrosis-specific contrast agent Gadophrin-3 was administered to all animals to delineate infarction on multislice T1-weighted spin-echo MRI. Nicorandil increased ischemic tolerance of LV hypertrophy as shown by the reduction of infarction size from 19.3% ± 1.3% to 10.0% ± 2.5% LV ( P= .005). Infarction size in treated animals was identical to control (9.3% ± 1.6%). Close correlation was found between MRI and postmortem findings. Functional MRI revealed an improvement in ejection fraction in nicorandil-treated hearts (48.5% ± 3.4% vs 38.1% ± 3.2%, P = .04). LV end-diastolic volume and pressure, aortic pressure, and peripheral vascular resistance were highest in untreated hypertrophied hearts. Brief ischemia caused severe injury in hypertrophied hearts. Infusing nicorandil increased the tolerance of hypertrophied hearts to ischemia. MRI is a suitable technique for the evaluation of new therapies in LV hypertrophy.
Long-Term Combination Therapy with Aspirin and Clopidogrel
Authors: Kumana C. R. , Cheung Giselle , Lauder I. J. , Cheung B. M. Y.
Published: March 2006

The possible additive antiplatelet effects of aspirin and clopidogrel have been explored in the Clopidogrel in Unstable Angina to Prevent Recurrent Events (CURE) and Management of Atherothrombosis with Clopidogrel in High Risk Patients (MATCH) studies. To assess the overall absolute beneficial and/or harmful impact of aspirin and clopidogrel combination therapy compared with monotherapy with either drug, we analyzed the results from both trials in terms of number needed to treat per year. Treating between 35 and 204 at-risk patients for 1 year with combination therapy appeared to prevent 1 patient from experiencing an adverse primary cardiovascular outcome; whereas, about 1 in 63 such patients appeared liable to major bleeding during that period. We determined that the evidence to date indicates no overall advantage for combination therapy with anti-platelet drugs in preference to monotherapy.
The Burden of Atrial Fibrillation: Should We Abandon Antiarrhythmic Drug Therapy?
Authors: Dorian Paul , Mangat Iqwal , Pinter Arnold , Korley Victoria
Published: March 2006

Atrial fibrillation (AF) is the most common sustained arrhythmia, exacting a substantial toll in cardiovascular morbidity and mortality. Until recently, the prevailing philosophy has been that restoration and maintenance of normal sinus rhythm, as opposed to control of ventricular response rate, was the optimal approach to treatment of AF. A series of landmark trials (AFFIRM, RACE, STAF, and PIAF) have called this strategy into question, suggesting outcomes are equivalent with both approaches. These data do not mean that rhythm control is not beneficial, but highlight the limitations of current therapies to achieve and maintain sinus rhythm. Limitations of the rhythm-control strategy may be related to our difficulty in accurately documenting symptomatic benefit from this approach, the lack of efficacy and excessive adverse-effect burden associated with currently available antiarrhythmic agents, and selection biases in the enrollment of patients in clinical trials of rhythm control versus rate control, making the trials incompletely representative of the population eligible for therapy. New pharmacologic agents under development feature increased atrial selectivity or multi-channel-blocking properties (or both). As a result, these compounds may be more effective in prolonging atrial refractoriness and may also have reduced proarrhythmic potential. It is premature to abandon the concept of rhythm control in AF until we have trials designed to include younger and highly symptomatic patients, more sensitive tools to measure symptomatic improvement, and safer, more effective antiarrhythmic agents.
Vascular Effects of Natriuretic Peptides in Healthy Men
Authors: Komarek Marius , Bernheim Alain , Schindler Ruth , Steden Renate , Kiowski Wolfgang , Rocca Hans Peter Brunner-La
Published: March 2006

Background: Most effects of atrial (ANP) and B-type natriuretic peptide (BNP) result from stimulation of the guanylyl-cyclase type A receptor. Chronic elevation causes hyporesponsiveness to ANP, whereas BNP effects tend to be preserved, implying an additional pathway of action. We, therefore, investigated the hemodynamic effects of co-infusion of ANP, BNP, and, as a positive control acting on type B receptor, C-type natriuretic peptide (CNP). Furthermore, vascular responses to short and prolonged infusions were compared to investigate rapid hyporesponsiveness of guanylyl-cyclase type A receptor.

Methods: In 11 healthy volunteers, arterial response to continuous intra-arterial infusion of ANP (60 pmol/100 mL forearm tissue volume [FAV]/min) was assessed by venous occlusion plethysmography. Then, co-infusion of a similar dose of ANP, BNP, or CNP was administered in randomized order. Each infusion phase was followed by a washout period. Then, ANP was restarted, followed by co-infusion of one of the natriuretic peptides not yet infused. After a further washout period, ANP was restarted, followed by co-infusion of the natriuretic peptide not yet co-infused. In 6 subjects, infusion time was adjusted to plasma half-lives (5 times), and in the other 5 subjects, infusion time was 5 minutes.

Results: ANP alone caused the expected vasodilation from 2.7 ± 0.3 mL/min/100 mL FAV to 6.0 ± 0.9 mL/min/100 mL FAV ( P < .004). This response remained unchanged in the group that received short-term infusions (6.2 ± 0.8 mL/min/100 mL FAV to 6.6 ± 1.1 mL/min/100mL FAV) but was reduced over time in the group receiving longer-term infusions (6.5 ± 1.2 mL/min/100 mL FAV to 4.5 ± 0.7 mL/min/100mL FAV, P < .05; difference between groups P < .05). Co-infusions of ANP, BNP, and CNP caused minor additional vasodilation (mean 0.8 ± 0.2 mL/min/100ml FAV, P < .01), which did not differ between the different co-infused natriuretic peptides.

Conclusion: Our data provide evidence for rapid desensitization of the guanylyl-cyclase type A receptor in humans, but do not support the presence of a BNP-specific receptor.
Monocyte Chemoattractant Protein 1-Induced Monocyte Infiltration Produces Angiogenesis but Not Arteriogenesis in Chronically Infarcted Myocardium
Authors: Schwarz Ernst R. , Meven Dennis A. , Sulemanjee Nasir Z. , Kersting Philipp H. , Tussing Tanja , Skobel Erik C. , Hanrath Peter , Uretsky Barry F.
Published: March 2006

Background: Monocyte chemoattractant protein 1 (MCP-1) stimulates the invasion of monocytes into ischemic tissue with concomitant adhesion to endothelial cells. Monocyte stimulation has been shown to be involved in the induction of arteriogenesis, which is the development of functional arterioles resulting in improvement of perfusion. However, angiogenesis (newly developed capillaries contribute to improved tissue perfusion) in several models has not resulted in any improvement in blood flow.

Objective: The effects of MCP-1 on potential angiogenesis and arteriogenesis as well as changes in left ventricular function were tested in a chronic infarct model in rat hearts.

Methods: Anesthetized rats were subjected to open-chest ligation of the left coronary artery with subsequent myocardial infarction. After 6 weeks, animals were randomized to receive either MCP-1 (3 µL in 0.15 mL NaCl, group 1, n = 9) or saline (0.15 mL, group 2, n = 9), which was injected into the myocardium at the border zones of the infarcts. For assessment of left ventricular dimensions and global cardiac function, transthoracic two-dimensional echocardiography was performed at baseline, 6 weeks after myocardial infarction, and 4 weeks after MCP-1 or saline injection, by use of a 12-MHz pediatric transducer. For light microscopic analysis, myocardial tissue was stained with Elastica-van-Giesson and von Willebrand factor for blood vessels and endothelial cells, respectively. In a subset of animals, hearts were excised 24 hours after MCP-1 administration (n = 4) or saline administration (n = 4) for assessment of monocyte infiltration by immunohistologic staining of the CD31 antigen.

Results: Left ventricular dimensions and ejection fraction changed after coronary occlusion (from 60.4% ± 2.85% to 24.8% ± 5.01% ejection fraction in group 1, and from 58.4% ±2.06% to 26.3% ± 4.3% ejection fraction in group 2 at 6 weeks, P < .005) without any further change 4 weeks after treatment (ejection fraction in group 1, 26.3% ± 2.7%, ejection fraction in group 2, 25.0% ± 5.18%). The MCP-1 group resulted in 390.6 ± 10.36 endothelial cells compared with 285.2 ± 13.56 in group 2 ( P < .005) at the injection site. Monocyte infiltration was observed at the MCP-1 injection site with an increase in capillary growth (angiogenesis). However, there was no difference in the number of arteriolar structures between animals treated with MCP-1 and saline animals (group 1, 19.0 ± 1.52 vs group 2,16.4 ± 0.68, P > .05).

Conclusion: A single intramyocardial injection of MCP-1 into the infarct border zone resulted in neo-angiogenesis and monocyte infiltration but not arteriogenesis in the rat heart. There was no functional change of chronically infarcted myocardium in the present model.
Case Report: Aortic Dissection and Cystic Medial Degeneration in a 24-Year-Old Without Marfan Syndrome
Authors: Caraang Chris , El-Bialy Adel
Published: March 2006

The effective management of aortic dissection relies heavily on a high index of suspicion followed by timely definitive diagnosis. Young adults without a history of blunt trauma who are not at risk for atherosclerotic disease may lower this suspicion. We present a 24-year-old patient with complaints of chest pain who presented in multiple urgent care clinics and emergency departments. With a normal chest radiograph, he was repeatedly discharged home on analgesics until a loud murmur was heard. An echocardiogram revealed a dilated aortic root with an intimal flap consistent with a type II dissection. After surgical aortic repair with a Bentall procedure, he was discharged with complete relief of symptoms. Histologic reports revealed cystic medial degeneration. Physical examinations did not demonstrate the phenotypic manifestations of Marfan syndrome. This case illustrates the importance of cardiac auscultation when assessing an individual with chest pain, even with a low likelihood for alteration in arterial structure, and the maintenance of a high index of clinical suspicion despite a normal chest radiograph. We consider this case to be of interest because of its rarity in a 24-year-old.
Effect of Flaxseed Consumption on Blood Pressure, Serum Lipids, Hemopoietic System and Liver and Kidney Enzymes in Healthy Humans
Authors: Stuglin Carlo , Prasad Kailash
Published: March 2006

Background: Effects of flaxseed on serum lipids have been studied in humans, but the results are variable. Flaxseed is ineffective in lowering blood pressure in rats. Its effect on blood pressure in humans is not known. It is also not known if long-term use of flaxseed in humans has deleterious effects on the hemopoietic system, serum glucose, and renal and kidney function. We investigated the effect of short-term use of flaxseed in humans on arterial pressure and serum lipids (triglycerides, total cholesterol; high-, low-, and very-low-densitylipoprotein cholesterol [HDL-C, LDL-C, VLDL-C], hemopoietic system (red blood cells, neutrophils, hemoglobin) and the various biochemical parameters, such as serum protein, albumin, total bilirubin, aspartate aminotransferase, alkaline phosphatase, creatinine, urea, related to hepatic and renal function, and serum glucose.

Methods: Fifteen healthy men, aged 22 to 47 years, consumed three muffins daily containing 32.7 g of total flaxseed for 4 weeks, in addition to their normal daily diet. Blood pressure and blood samples for various biochemical measurements were collected before and after 4 weeks of flaxseed diet.

Results: Blood pressures, heart rate, hemoglobin, and counts of red blood cells, white blood cells, and neutrophils remained unaltered after flaxseed diet. Serum total cholesterol, HDLC, LDL-C, and VLDL-C remained unchanged, but serum triglycerides levels were elevated. Serum total bilirubin, aspartate aminotransferase, alkaline phosphatase, protein, albumin, glucose, and urea remained unaltered, but serum levels of creatinine decreased.

Conclusion: These results suggest that 4 weeks use of flaxseed does not have deleterious effects on the hemopoietic system or renal and hepatic function and does not lower blood pressure and serum lipids. However, the level of serum triglyceride level was elevated.
Long-Term Benefits and Limitations of Combined Antianginal Drug Therapy in Elderly Patients with Symptomatic Chronic Coronary Artery Disease
Authors: Bonetti Piero O. , Kaiser Christoph , Zellweger Michael J. , Grize Leticia , Erne Paul , Schoenenberger Ronald A. , Pfisterer Matthias E. ,   TIME Investigators
Published: March 2006

Background: Chronic angina is a common and disabling disorder in the elderly. Combined antianginal drug treatment represents the mainstay of therapy in this population. However, there is a paucity of data regarding the effect of this strategy on long-term outcome in the elderly.

Methods: To assess the long-term effect of combined antianginal drug therapy in elderly individuals, we performed a long-term follow-up analysis of all 148 patients of the Trial of Invasive versus Medical therapy in Elderly (TIME) patients with chronic symptomatic coronary-artery disease assigned to an optimized medical therapy strategy. Angina severity, measures of quality of life (QOL), and survival were assessed after a median of 3.7 (0.1-6.9) years.

Results: At baseline, patients were 79.8 ± 3.5 years old with Canadian Cardiovascular Society (CCS) class angina 3.0 ± 0.7 despite the use of 2.4 ± 0.6 antianginal drugs. Although antianginal drugs were increased to 2.8 ± 0.9 ( P < .01), 63 (43%) patients needed revascularization for refractory symptoms during the first year of observation (REVASC). At baseline, REVASC patients had more frequently CCS class 4 angina (37% vs 20%, P < 0.05) but reported less prior heart failure (5% vs 20%, P < 0.01), fewer prior cerebral events (3% vs 13%, P < .05) and a lower rate of two or more comorbidities (10% vs 33%, P < .01) than patients on continued drug therapy (DRUG). At long-term follow-up, angina severity was still higher in DRUG compared to REVASC patients (CCS class, 1.8 ± 1.6 vs 1.0 ± 1.4, P < .05) despite more antianginal drugs (2.1 ± 1.1 vs 1.5 ± 1.0, P < .01), whereas measures of QOL had improved similarly in both groups. In addition, long-term mortality was significantly higher in DRUG than in REVASC patients (38% vs 13%, P < .01).

Conclusion: Combined antianginal drug therapy successfully relieved symptoms in most elderly patients with chronic angina but failed to do so in 43%. Patients who needed revascularization for refractory symptoms reported less angina, despite lower drug use during long-term follow-up and had a better long-term survival. Thus, the widely used strategy to increase antianginal drug therapy in elderly patients instead of evaluating them for revascularization should be reconsidered.
Cardiovascular Risk of Selective Cyclooxygenase-2 Inhibitors
Authors: Schrör Karsten , Mehta Paulette , Mehta Jawahar L.
Published: March 2006

Recently, cyclooxygenase-2 (COX-2) inhibitors (coxibs), a class of drugs intended to be painkillers, have created unprecedented controversy because of their cardiovascular risk profile. The controversy has affected the patients, health-care providers, the Food and Drug Administration, and the manufacturers of these agents alike. We summarize the mechanisms of actions of this class of agents, their cardiovascular risk as evident in multiple trials, the basis of their adverse risk profile, and our views on this issue.
Myocardial Calcification as a Rare Cause of Congestive Heart Failure: A Case Report
Authors: El-Bialy Adel , Shenoda Michael , Saleh Jahandar , Tilkian Ara
Published: March 2006

Myocardial calcification is a manifestation of either metastatic or dystrophic calcium deposition in the myocardium. Dystrophic calcification of the myocardium is most commonly seen in long-term survivors of substantial myocardial infarctions. Current literature has reported only 3 cases of myocardial calcification with normal coronary arteries. We present a case of an 80-year-old woman with multiple admissions over a 5-year period for congestive heart failure. She was found to have a normal left ventricular ejection fraction and normal coronary arteries on left heart catheterization. A high resolution computed tomography (CT) study of the chest revealed extensive left ventricular myocardial calcifications, which were not present 4 years earlier on CT. The patient’s history and clinical presentation revealed no etiologic factors for her calcified myocardium.
Simple Clinical Criteria to Determine the Prognosis of Heart Failure
Authors: Heywood J. Thomas , Elatre Wafaa , Pai Ramdas G. , Fabbri Sharon , Huiskes Bonnie
Published: March 2006

Objective: To determine whether easily obtained clinical parameters serve as predictors of survival in patients with congestive heart failure. Several scoring systems to predict heart failure survival have been developed; however, many of these deal principally with transplant recipients or do not account for a patient’s response to therapy.

Methods: A total of 680 patients with an ejection fraction of less than 40% were included in the analysis. Baseline assessments were performed and treatment regimens were identified; patients were then followed for up to 5 years. Univariate and multivariate Cox regression models were used to determine clinically important predictors of survival. Kaplan-Meier survival functions for patients with and without the prognostic variable were constructed and mortality was calculated at 1 year and 5 years.

Results: Ejection fraction improvement at 6 months, diabetes mellitus, age, serum creatinine, and blood urea nitrogen (BUN) were significant predictors for survival in the univariate model. Ejection fraction improvement, age, and BUN were significant predictors in the multivariate model. These findings were used to construct a model for predicting patient mortality. Improved ejection fraction (>15 ejection fraction units) gave a 1-year mortality of 2% and a 5-year mortality of 11%. Mortality rates according to patient age and BUN levels were also calculated.

Conclusion: Ejection fraction improvement was the most important predictor for survival in patients with systolic dysfunction; monitoring ejection fraction changes through repeat echocardiograms has important prognostic value. In patients without ejection fraction improvement, age and renal function are important survival determinants.
Marked QT Prolongation and Torsades de Pointes Secondary to Acute Ischemia in an Elderly Man Taking Dofetilide for Atrial Fibrillation: A Cautionary Tale
Authors: Nagra Bipinpreet S. , Ledley Gary S. , Kantharia Bharat K.
Published: March 2006

Dofetilide has been shown to be effective and safe in maintaining sinus rhythm in patients with persistent atrial fibrillation and congestive heart failure. Because of serious side effects of an increase in the QT interval causing torsades de pointes, dofetilide must be initiated with close monitoring of the QT interval in an inpatient setting. However, little has been reported about conditions surrounding the change in QT interval after the steady state is achieved that may have implications in the safety and efficacy of the drug. We report marked QT prolongation and torsades de pointes in a setting of flash pulmonary edema resulting from acute myocardial ischemia in a patient who was being treated with dofetilide for atrial fibrillation. Our case reminds the clinicians that the adverse and proarrhythmic effects of dofetilide can occur due to changes in the arrhythmic substrate during acute severe ischemia.
Beneficial Cardiovascular Actions of Eplerenone in the Spontaneously Hypertensive Rat
Authors: Susic Dinko , Varagic Jasmina , Ahn Jwari , Matavelli Luis C. , Frohlich Edward D.
Published: March 2006

Background: Aldosterone has been implicated as a potential mediator of cardiac and vascular damage in a variety of disorders. This study examined the role of aldosterone and its interplay with the renin-angiotensin system in the pathogenesis of hypertension. To this end, the effects of the aldosterone antagonist eplerenone and the angiotensin converting enzyme inhibitor lisinopril on cardiovascular mass, myocardial collagen, and coronary circulation were examined in spontaneously hypertensive rats.

Methods: Male, 22-week-old rats were randomly divided into 4 groups (12 in each). The control group received no treatment, the second group was given eplerenone (100 mg/kg/day), the third received lisinopril (3 mg/kg/day), and the fourth was given eplerenone and lisinopril. After 12 weeks of respective treatments, systemic and regional hemodynamics and cardiovascular mass indexes were measured in conscious instrumented rats.

Results: Eplerenone decreased arterial pressure but did not affect left ventricular mass or hydroxyproline concentration (an estimate of collagen). It did, however, reduce minimal coronary vascular resistance and increased coronary flow reserve. Lisinopril decreased arterial pressure and ventricular mass but did not affect regional hemodynamics. The combination therapy produced synergistic effects.

Conclusion: Aldosterone antagonism improved coronary and systemic hemodynamics in adult spontaneously hypertensive rats but did not affect cardiovascular mass indexes. The finding that lisinopril and eplerenone decreased arterial pressure to the same extent but had different cardiovascular effects suggested that these effects might be pressure independent.
Do All Patients With Coronary Artery Disease Benefit from Angiotensin Converting Enzyme Inhibitors?
Authors: Shah Apurva D. , Arora Rohit R.
Published: March 2006

Cumulative evidence supports the use of angiotensin-converting enzyme (ACE) inhibitors for stable coronary artery disease in patients with and without heart failure. The dose and unique properties of ACE inhibitors, trial data, differences in trial design and demographics, may all contribute to variable responses in clinical outcomes. Pending direct comparator clinical trials between a tissue ACE inhibitor vs a plasma ACE inhibitor, evidence indicates that both ramipril and perindopril can be recommended for secondary risk prevention.
Current Debates in Antiphospholipid Syndrome: The Acquired Antibody-Mediated Thrombophilia
Authors: Öztürk M. Akif , Haznedaroğlu Ibrahim C. , Turgut Mehmet , Göker Hakan
Published: March 2006

Antiphospholipid (APL) syndrome is the most common form of acquired thrombophilia. It can cause significant morbidity and even mortality. The term “APL antibodies” represents a heterogeneous group of antibodies associated with this disorder. Currently no single assay can identify every APL antibody. Clinically relevant APL antibodies are mainly anticardiolipin antibodies (ACA) detected by solid phase enzyme-linked immunosorbent assay (ELISA) and lupus anticoagulants (LA) demonstrated by in vitro coagulation assay. However, there are some other antibodies associated with the APL syndrome (i.e., subgroup APL antibodies). ACAs, LAs, and subgroup APL antibodies represent intersecting, but non-identical, subsets of autoantibodies. Thus, those autoantibodies may coexist or may occur independently. Any organ system and any size of vessel can be affected during the clinical course of the disease. Therefore, the APL syndrome can manifest itself in a wide variety of clinical thrombotic features. Fetal loss and pregnancy morbidity represent a specific challenge. Despite tremendous advances in the understanding of the pathogenesis of APL syndrome during the past decade, the mainstay of management is still anticoagulation. However, there is no general agreement regarding the duration and intensity of anticoagulant therapy. In this review, we focused on the current dilemmas and their present clarifications in the wide clinicopathologic spectrum of APL syndrome and APL antibody-related distinct pathologic conditions.
Effects of Losartan and Simvastatin on Monocyte-Derived Microparticles in Hypertensive Patients With and Without Type 2 Diabetes Mellitus
Authors: Nomura Shosaku , Shouzu Akira , Omoto Seitaro , Nishikawa Mitsushige , Iwasaka Toshiji
Published: March 2006

Monocyte-derived microparticles play an important role in the pathogenesis of diabetic vasculopathy, and angiotensin II receptor blocker and statin have been shown to have a beneficial effect on the angiopathies of hypertension and hyperglycemia in patients with type 2 diabetes mellitus. However, the interaction between angiotensin II receptor blocker and statin, and monocyte-derived microparticles in atherosclerosis is poorly understood. The effects of losartan and simvastatin on circulating concentrations of monocyte-derived microparticles, chemokines, and soluble adhesion markers were studied in hypertensive patients with or without type 2 diabetes mellitus. Monocyte-derived microparticles were measured by flow cytometry, and levels of serum chemokines (MCP-1 and RANTES) and soluble adhesion markers (sP-selectin and sVCAM-1) were measured by enzyme-linked immunosorbent assay. Losartan decreased both the systolic and diastolic blood pressure in hypertensive patients with and without type 2 diabetes mellitus. The concentrations of monocyte-derived microparticles, chemokines, and soluble adhesion molecules were higher in hypertensive patients who also had type 2 diabetes mellitus vs. those who did not. The administration of angiotensin II receptor blocker decreased the circulating concentration of all these markers. In addition, all markers were decreased by combination therapy, and monocyte-derived microparticles were decreased more with combination therapy with losartan and simvastatin than monotherapy with losartan. The administration of angiotensin II receptor blocker inhibited monocyte-derived microparticle generation and suggests that angiotensin II is intimately related to vascular changes that occur in type 2 diabetes mellitus. Combination therapy with a statin and angiotensin II receptor blocker might be valuable as anti-atherosclerotic therapy in patients with type 2 diabetes mellitus and nephropathy.
Effect of Ticlopidine on Monocyte-derived Microparticles and Activated Platelet Markers in Diabetes Mellitus
Authors: Shouzu Akira , Nomura Shosaku , Omoto Seitaro , Hayakawa Takashi , Nishikawa Mitsushige , Iwasaka Toshiji
Published: March 2006

Platelet-derived microparticles, activated platelets, and monocyte-derived microparticles were measured in 73 patients with diabetes mellitus. A comparative study of these parameters was performed before and after administration of ticlopidine. The number of platelet-derived microparticles and activated platelets was increased significantly in diabetic patients. Monocyte-derived microparticles were also increased significantly. After administration of ticlopidine, platelet-derived microparticles and activated platelets corrected positively, not only CD62P- and CD63-positive platelets, but also platelet-derived microparticles and monocyte-derived microparticles showed a significant decrease. These data suggest that in patients with diabetes, platelet-derived microparticles and activated platelets stimulate the activation of monocytes and promote the production of monocyte-derived microparticles, and that ticlopidine is useful for hypercoagulabillity in diabetic patients.
Plateletcrit, Mean Platelet Volume, Platelet Distribution Width: Its Expected Values and Correlation With Parallel Red Blood Cell Parameters
Authors: Wiwanitkit Viroj
Published: March 2006

The quantitation of platelets in peripheral blood is a well-recognized tool. Recently, new indices related to erythrocytes and platelet counts have been provided by hematologic analyzers. Concerning the platelet parameter, the three important parameters are plateletcrit (PCT), mean platelet volume (MPV), platelet distribution width (PDW). The purpose of the study is to investigate these three parameters to define their expected values and the correlation with the parallel red blood cell parameters, hematocrit (HCT), mean corpuscular volumer (MCV), and red blood cell distribution width (RDW). Blood samples form 215 volunteers were analyzed for platelet parameters using Technicon H*3. The average (mean ± SD) values obtained with expected ranges were PCT 0.24 ± 0.05% (range, 0.23-0.24%), MPV 12.79 ± 5.91 fL (range, 12.39-13.19 fL), and PDW 46.79 ± 2.70% (range, 46.61-46.97%). Concerning the correlation between PCT, MPV, and RDW and their parallel red blood cell parameters, there was no significant correlation between PCT and HCT, and between MPV and MCV. However, there was a significant correlation between PDW and RDW. It seems that the anisocytosis of red blood cells and platelets might co-occur. However, these data are basic observations; further in-depth evaluation of the platelet parameters is recommended.
Prevalence of β2-Glycoprotein I Antibody in Patients with Liver Cirrhosis: Relationship with β2-Glycoprotein I Plasma Levels and Thrombosis
Authors: Song Kyung Soon , Kim Hyun Kyung
Published: March 2006

Recently, a semiquantitative enzyme-linked immunoassay for detecting IgG or IgM class autoantibody to β2-GPI for use as an aid in the diagnosis of certain autoimmune or thrombotic disorders. We evaluated the prevalence of anti-β2-GPI antibody and its relation to plasma β2-GPI levels and occurrence of thrombosis in 69 patients with liver cirrhosis. As expected, plasma β2-GPI levels were lower in the patients with liver cirrhosis and correlated with Child classification. Anti-β2-GPI antibodies were positive in 11 (15.9%) patients. However, there were no differences in β2-GPI levels, platelet counts, and thrombosis between positive and negative groups for anti-β2-GPI antibodies.
A Practical Concept for Preoperative Identification of Patients with Impaired Primary Hemostasis
Authors: Koscielny Juergen , Ziemer Sabine , Radtke Hartmut , Schmutzler Michael , Pruss Axel , Sinha Pranav , Salama Abdulgabar , Kiesewetter Holger , Latza Reinhard
Published: March 2006

The findings of a large prospective study designed to identify primary and/or secondary hemostatic disorders before surgical interventions are presented. A total of 5649 unselected adult patients were enrolled to identify impaired hemostasis before surgical interventions. Each patient was asked to answer a standardized questionnaire concerning bleeding history. Activated partial thromboplastin time (aPTT), prothrombin time (PT), and platelet counts (PC) including PFA-100 (platelet function analyzer): collagen-epinephrine (C/E), and collagen-ADP (C/ADP) were routinely done in all patients. Additional tests, bleeding time (BT), and von Willebrand factor (vWF: Ag) were performed only in patients with a positive bleeding history and/or evidence of impaired hemostasis; e.g., drug ingestion. The bleeding history was negative in 5021 patients (88.8%) but positive in the remaining 628 (11.2%). Impaired hemostasis could be verified only in 256 (40.8%) of these patients. The vast majority were identified with PFA-100: C/E (n=250; 97.7%). The other six patients with impaired hemostasis were identifiable solely based on the PT (n=2), PFA-100: C/ADP (n=2), and vWF: Ag (n=2). The PFA-100: C/ADP detected 199 patients (77.7%). The only abnormality found among patients with a negative bleeding history was a prolonged aPTT due to lupus anticoagulant in nine patients (0.2%). The sensitivity of the PFA-100: collagen-epinephrine was the highest (90.8%) in comparison to the other screening tests (BT, aPTT, PT, vWF: Ag). The positive predictive value of the PFA-100: collagen-epinephrine was high (81.8%), but the negative predictive value was higher (93.4%). The use of a standardized questionnaire and, if indicated, the PFA-100: C/E and/or other specific tests not only ensure the detection of impaired hemostasis in almost every case but also a significant reduction of the cost.
Activated Platelet and Oxidized LDL Induce Endothelial Membrane Vesiculation: Clinical Significance of Endothelial Cell-Derived Microparticles in Patients With Type 2 Diabetes
Authors: Nomura Shosaku , Shouzu Akira , Omoto Seitaro , Nishikawa Mitsushige , Iwasaka Toshiji , Fukuhara Shirou
Published: March 2006

Endothelial cells, platelets, and oxidized LDL could play very important roles in the development of atherosclerosis in diabetes patients. The levels of plasma endothelial cell-derived microparticles (EDMP), platelet-derived microparticles (PDMP), platelet-P-selectin (plt-PS), soluble CD40 ligand (sCD40L), and anti-oxidized LDL antibody were measured and compared to develop a better understanding of their potential contribution to diabetic vascular complications. The concentrations of EDMP, PDMP, plt-PS, and sCD40L in diabetic patients were significantly higher than those in normal subjects. The number of EDMPs in patients with diabetes complicated by nephropathy was significantly higher than that in those without complications. Levels of anti-oxidized LDL antibody were also higher in type 2 diabetic patients than in control subjects. In addition, anti-oxidized LDL antibody levels correlated with EDMP, PDMP, plt-PS, and sCD40L levels in nephropathy patients. In the nephropathy group treated with sarpogrelate hydrochrolide, a 5-HT2A receptor antagonist, EDMP, PDMP, plt-PS, and sCD40L levels were decreased significantly. Oxidized LDL increased expression of plt-PS, and also promoted shedding of PDMP. Furthermore, oxidized LDL promoted a dose-dependent release of 5-hydroxytriptamine. On the other hand, activated platelets and PDMP promoted endothelial cells and THP-1 (monocytic cell line) interaction, and membrane vesiculation occurred in the presence of oxidized LDL. These findings suggest that activated platelets and oxidized LDL induce EDMP generation, and that elevated EDMPs may be a sign of vascular complications in type 2 diabetic patients, particularly those who suffer from diabetes-associated nephropathy
Age-Dependent Likelihood of In Situ Thrombosis in Secondary Pulmonary Hypertension
Authors: Caramuru Lúcia H. , Maeda Nair Y. , Bydlowski Sérgio P. , Lopes Antonio Augusto
Published: March 2006

Pulmonary arterial thrombosis (PAT) may complicate the clinical course of pulmonary hypertension associated with congenital heart disease (so-called Eisenmenger syndrome, ES). In this study, variables were sought that could represent risk factors for the occurrence of this complication. Twenty patients aged 11 to 53 (median, 33) years were studied. The presence of PAT (spiral computed tomography angiography) was correlated with age, gender group, PAP, hematocrit, peripheral oxygen saturation (SpO2), and plasma levels of endothelial and coagulation dysfunction markers: von Willebrand factor antigen (vWF: Ag), tissue plasminogen activator (t-PA), and D-dimer (enzyme immunoassay). Patients were classified according to the presence (group 1, N=7), or absence (group 2, N=13) of PAT. Group 1 patients were older (42±8 vs. 27±10 years in group 2, p=0.0051), had lower SpO2 (82±7% vs. 89±6% in group 2, p=0.0462) and increased D-dimer levels (637 vs. 149 ng/mL in group 2, median values, p=0.0235). A trend was observed toward an increase in vWF: Ag (125±29 vs. 103±18 U/dL in group 2, p=0.0789) and t-PA (15.7 vs. 9.4 ng/mL in group 2, median values, p=0.0689). Age was the main variable influencing the occurrence of PAT in multivariate analysis (p=0.0026), with odds ratio of 1.204 per year. The age of 35 years was 86% sensitive and 85% specific for occurrence of PAT. Age correlated positively with t-PA (r=0.57, p=0.0111). Thus, PAT is highly prevalent in ES as an age-dependent event, probably associated with endothelial dysfunction. Prophylactic anticoagulation should be considered before the age of 30 years, in particular in subjects with low SpO2 and increased D-dimer levels.