bluuebunny/crossref_metadata_2025 huggingface dataset:
Relation of iodine‐123 metaiodobenzylguanidine myocardial scintigraphy to endomyocardial biopsy findings in patients with dilated cardiomyopathy
Authors: Murata Katsutoshi , Kusachi Shozo , Murakami Takashi , Nogami Kunio , Murakami Masahiro , Hirohata Satoshi , Tominaga Youkou , Komatsubara Issei , Tsuji Takao
Published: February 2009

Background:Iodine‐123 metaiodobenzylguanidine (123I‐MIBG) concentrates in adrenergic neurons and has been developed for evaluation of the sympathetic nervous system. Recent studies have demonstrated that the normal heart is clearly visualized by123I‐MIBG cardiac scintigraphy, whereas abnormal123I‐MIBG myocardial uptake and washout have been demonstrated in patients after myocardial infarction and in patients with congestive cardiomyopathy, long QT syndrome, and ventricular tachycardia.

Hypothesis:Based on evidence from recent studies, it can be hypothesized that123I‐MIBG uptake is related to histopathologic changes in the myocardium.

Methods:The relation of123I‐MIBG uptake to the histologic findings for the heart was studied in 24 patients with dilated cardiomyopathy (DCM). The study group did not include patients with complicating disorders that primarily affect the adrenergic nervous system. The123I‐MIBG uptake was visually assigned one of four grades using the two criteria of the mean score for six regional uptake grades (mean score) and the global score obtained by visual evaluation of the entire image (global score). The123I‐MIBG uptake score was also determined for the region at which the biopsy specimen was obtained (biopsy region score). The histologic findings were evaluated by assigning one of four grades for each of the following five factors: myocyte hypertrophy, myocardial fibrotic change, myocyte degeneration and necrosis, mononuclear cell infiltration, and myocyte disarray. The sum for all grades was defined as the total score, and the global score was also assigned to the overall histologic findings.

Results:All of the global, mean, and biopsy region scores for123I‐MIBG uptake correlated significantly with the global and total scores for the histologic findings. Among the histologic factors, myocyte degeneration showed score correlated with all global, mean, and biopsy region scores for the uptake. Myocyte hypertrophy was associated weakly with the123I‐MIBG uptake scores.

Conclusion:These results indicate that123I‐MIBG uptake imaging is associated with histopathologic abnormalities in patients with DCM.
Dynamic three‐dimensional echocardiography in the assessment of cor triatriatum
Authors: Melzer Christoph , Bartel Thomas , Müller Silvana , Kleber Franz Xaver , Baumann Gert
Published: February 2009

Classic cor triatriatum sinistrum is a rare cardiac malformation to be found in the adult. One year after surgical correction of an atrial septal defect in a 55‐year‐old man, cor triatriatum sinistrum was diagnosed by transesophageal echocardiography. We compared transthoracic echocardiography, transesophageal echocardiography, and cardiac catheterization to dynamic three‐dimensional echocardiography (3‐D echo) which offers a new, noninvasive approach to determine the opening size between the accessory and the true left atrium. The findings by 3‐D echo, confirmed by left heart catheterization, showed that the accessory membrane was not stenosing. Surgical correction was therefore not indicated in this patient.
The vital role of papillary muscles in mitral and ventricular function: echocardiographic insights
Authors: Madu Ernest C. , D'Cruz Ivan A.
Published: February 2009

The two left ventricular (LV) papillary muscles are small structures but are vital to mitral valve competence. Partial or complete rupture, complicating acute myocardial infarction, causes severe or even catastrophic mitral regurgitation, potentially correctable by surgery. Papillary muscle dysfunction is a controversial topic in that the role of the papillary muscle itself, in causing mitral regurgitation post infarction, has been seriously questioned; it is less confusing if this syndrome is attributed not only to papillary muscle but also to adjacent LV wall ischemia or infarction. Papillary muscle calcification is easily and frequently detected on echocardiography, but its clinical significance remains uncertain. Papillary muscle hypertrophy accompanies LV hypertrophy of varied etiology and may have a significant role in producing dynamic late‐systolic intra‐LV obstruction in hypertrophic cardiomyopathy and other hyperdynamic hypertrophied LV chambers. All the above abnormalities can be adequately assessed by 2‐D echocardiography and the Doppler modalities. In selected cases, transesophageal echocardiography can provide additional valuable data by improving visualization of papillary muscles and mitral apparatus.
Depression and coronary heart disease: A review for cardiologists
Authors: Carney Robert M. , Freedland Kenneth E. , Sheline Yvette I. , Weiss Edward S.
Published: February 2009

Major depression is a common comorbid condition in patients with coronary heart disease (CHD). Although mild emotional distress may be a normal reaction to myocardial infarction or other manifestations of CHD, major depression should not be considered a normal reaction, nor should it be ignored. Major depression is a debilitating comorbid disorder that can seriously complicate recovery and increase the risks of further cardiac morbidity and mortality. Fortunately, it is one that can be successfully treated in the majority of cases. The purpose of this review is to present the evidence for the negative prognostic effects of depression in cardiac patients and to discuss methods for assessing and treating depression in these patients.
Modification of the circadian pattern of ventricular tachyarrhythmias by beta‐blocker therapy
Authors: Behrens Steffen , Ehlers Christoph , Brüggemann Thomas , Ziss Wolfgang , Dissmann Rüdiger , Galecka Miroslawa , Willich Stefan N. , Andresen Dietrich
Published: February 2009

Background: Sudden cardiac death exhibits a circadian variation and predominantly occurs during morning hours. Beta‐adrenergic antagonists have shown to blunt this morning peak. However, previous reports studying the effects of beta blockers on the circadian variation did not analyze the underlying cause of sudden cardiac death. It thus remains unclear whether ventricular tachyarrhythmias are influenced by beta‐blocker therapy.

Hypothesis: This study tested the hypothesis that beta‐blocking agents blunt the morning peak of life‐threatening ventricular tachyarrhythmias.

Methods: In 87 patients who were treated and monitored with an implantable cardioverter defibrillator, the circadian distribution of ventricular tachyarrhythmias terminated by appropriate shocks was analyzed and compared in those receiving beta blockers versus those not receiving beta‐blocker therapy.

Results: Tachyarrhythmic episodes in the absence of beta‐blocker therapy (n = 344) exhibited a circadian variation with a distinct morning peak (16, 38, 28, and 18% of episodes at 0–6, 6–12, 12–18, and 18–24 h, respectively, p<0.001). In contrast, tachyarrhythmic episodes during beta‐blocker therapy (n = 104) were equally distributed over time (22, 27, 24, and 27% of episodes at 0–6, 6–12, 12–18, and 18–24 h, respectively, p = 0.95). The circadian distribution of episodes was significantly different in patients with and those without beta blockade (p<0.05).

Conclusion: Beta‐adrenergic antagonists influence the circadian distribution of malignant ventricular tachyarrhythmias in patients with an implantable cardioverter defibrillator. The blunted morning peak of tachyarrhythmic events during beta blockade supports the hypothesis that a sympathetic surge is involved in the circadian pattern of malignant arrhythmias.
Erythrocyte magnesium and prostaglandin dynamics in chronic sleep deprivation
Authors: Tanabe Kazuhiko , Osada Naohiko , Suzuki Noriyuki , Nakayama Masaru , Yokoyama Yasuhiro , Yamamoto Akiko , Oya Misa , Murabayashi Taizo , Yamamoto Masanobu , Omiya Kazuto , Itoh Haruki , Murayama Masahiro
Published: February 2009

Background and hypothesis: The mechanism of sudden cardiac death occurring in patients with chronic fatigue is controversial. This study was designed to define a hypothesis that coronary arterial spasm and thrombus formation can occur during chronic fatigue.

Methods: For evaluating the feasibility of coronary arterial spasm, erythrocyte magnesium (Mg) was measured. Blood coagulability was evaluated by the change of prostaglandin concentration. Subjects included 16 healthy male volunteers (mean age 21.6 ± 2.5 years). Test conditions were as follows: (A) control state: a day following a night of good sleep; (B) temporary sleep deprivation: a day preceded by < 3 h of sleep; (C) chronic sleep deprivation: a day preceded by a month during which sleep lasted < 60% of that in condition (A) above. The erythrocyte Mg concentration was measured by the atomic absorption method. The plasma concentration of thromboxane B2 and 6‐keto‐prostaglandin F1α were measured in eight subjects by radioimmunoassay method.

Results: (1) Mean erythrocyte Mg concentration was significantly less in chronic sleep deprivation (1.1 ±0.4 mg/dl) than in the control state (1.8 ± 0.4 mg/dl, p<0.01) or in temporary sleep deprivation (1.6 ± 0.4, p<0.01). (2) The level of thromboxane B2 was significantly higher during chronic sleep deprivation than under control conditions (104.4 ± 78.0 vs. 20.4 ± 9.0 pg/ml, p<0.05). (3) There were no significant intergroup differences in 6‐keto‐prostaglandin F1α level.

Conclusion: These findings could support the hypothesis that coronary arterial spasm and thrombus formation occur in chronic sleep deprivation.
A practical approach to torsade de pointes
Authors: Roden Dan M.
Published: February 2009

The term torsade de pointes refers to polymorphic ventricular tachycardia that occurs in the setting of an abnormally long QT interval. While the most common cause is treatment with QT prolonging drugs, torsade de pointes also occurs in the congenital long QT syndromes and in the setting of acquired heart block or severe electrolyte disturbance, notably hypokalemia. Among QT prolonging drugs that cause torsade de pointes, both antiarrhythmics and “noncardioactive” drugs have been recognized. The electrocardiographic features of torsade de pointes include labile QT intervals, prominent U waves, and a “pause‐dependent” onset of the arrhythmia. Treatment consists of recognition of the syndrome, correction of underlying electrolyte abnormalities, and withdrawal of any offending drugs. Magnesium, isoproterenol, or cardiac pacing provides specific antiarrhythmic therapy in torsade de pointes.
Atrial double potentials associated with a left‐sided accessory pathway having a single ventricular and two remote atrial insertions
Authors: Hluchy Jan , Lautermann Dirk , Sabin Georg V.
Published: February 2009

This paper reports the case of a 63‐year‐old female patient with Wolff‐Parkinson‐White syndrome who underwent an electrophysiologic study (EPS) and ablation using temperature‐guided radiofrequency current for atrial fibrillation with a shortest preexcited RR interval of 160 ms. Detailed EPS and mapping demonstrated an unusual, complex left‐sided accessory pathway, with the two distinct branches having two remote atrial insertions and a narrow common ventricular isthmus associated with the manifestation of atrial double potentials recorded from the coronary sinus. Simple ablation at the left lateral side from the ventricular aspect completely eliminated complex accessory pathway conduction, resulting in the disappearance of atrial double potentials.
Amiodarone in restoration and maintenance of sinus rhythm in patients with chronic atrial fibrillation after unsuccessful direct‐current cardioversion
Authors: Opolski Grzegorz , Stanislawska Jolanta , Górecki Aleksander , Świěcicka Grazyna , Kraska Tadeusz , Torbicki Adam
Published: February 2009

Background: When direct‐current (DC) cardioversion is used, sinus rhythm can be restored, at least temporarily, in 80–90% of patients with atrial fibrillation. However, there is a small but significant group of patients with chronic atrial fibrillation in whom DC cardioversion has failed to restore sinus rhythm. The value of antiarrhythmic drug pretreatment before DC cardioversion is still controversial.

Hypothesis: The aim of our study was to assess (1) the effecti veness of repeat DC cardioversion in patients with chronic atrial fibrillation after pretreatment with amiodarone, and (2) the efficacy of amiodarone in maintaining sinus rhythm after repeat cardioversion.

Methods: Forty‐nine patients with chronic atrial fibrillation after ineffective DC cardioversion were included in the study. Repeat DC cardioversion was performed after loading with oral amiodarone, 10–15 mg/kg body weight/day for a period necessary to achieve the cumulative dose of over 6.0 g.

Results: Spontaneous conversion to sinus rhythm during amiodarone pretreatment was achieved in 9 of 49 patients (18%). Direct‐current cardioversion was performed in 39 patients and sinus rhythm was achieved in 23 of these patients (59%). Mean heart rate decreased from 95 beats/min before to 68 beats/min after DC cardioversion (p<0.001). Systolic blood pressure significantly (p<0.05) decreased from 126 ± 23 to 108 ± 25 mmHg. Complications occurring in four patients just after electroconversion were well tolerated and of short duration. After 12 months, 52% of patients maintained sinus rhythm on low dose (200 mg/day) amiodarone therapy.

Conclusion: Pretreatment with amiodarone and repeat DC cardioversion allows for restoration of sinus rhythm in about 65% of patients with chronic atrial fibrillation after first ineffective DC cardioversion. Direct‐current cardioversion can be performed safely with the use of standard precautions in patients who are receiving amiodarone. At 12 months' follow‐up, more than 50% of patients maintain sinus rhythm on low‐dose amiodarone after successful repeat cardioversion.
Heart rate‐independent prolongation of QTc interval in women with syndrome X
Authors: Mammana Carmelo , Salomone Oscar A. , Kautzner Josef , Schwartzman Raúl A. , Kaski Juan Carlos
Published: February 2009

Background: Cardiac syndrome X is usually diagnosed in the presence of typical exertional chest pain, a positive response to exercise testing, and normal coronary angiograms. The underlying pathogenic mechanisms are speculative, but myocardial ischemia and increased sympathetic activity have been implicated.

Hypothesis: The present study examined whether QTc interval is prolonged in women with syndrome X when confounding factors such as heart rate, gender, and environmental conditions are accounted for.

Methods: Maximum QTc interval and its relationship to clinical and exercise variables were evaluated in 32 women with syndrome X (exertional chest pain, positive exercise testing, and completely normal coronary arteries) and 34 normal controls.

Results: Patients with syndrome X had significantly longer QTc interval (440 ± 24 ms) than normal subjects (410 ± 26 ms, p<0.004). However, this QTc prolongation appears to be heart rate‐independent as patients with syndrome X showed longer QT and QTc intervals than controls despite an identical heart rate. No relation was found between QTc prolongation and clinical or exercise test variables in patients with syndrome X.

Conclusion: Although increased sympathetic drive is present in syndrome X, and this variable is likely to modulate QTc duration, the mechanism and clinical implications of QTc interval prolongation in syndrome X remain speculative.
Plasma nitrite/nitrate level is inversely correlated with plasma low‐density lipoprotein cholesterol level
Authors: Tanaka Seiya , Yashiro Akira , Ikeda Masaharu , Kuroiwa Akio , Nakashima Yasuhide , Nanri Hiroki
Published: February 2009

Background: Plasma nitrite/nitrate (NOx) is a stable end product of the vasodilator nitric oxide (NO). However, there are few reports about plasma NOx levels in humans.

Hypothesis: The purpose of this study was to assess the availability of plasma NOx for evaluating basal endogenously‐synthesized or endothelium‐derived NO, and to examine whether NOx levels are lowered in patients with coronary artery disease (CAD) or its risk factors.

Methods: Plasma NOx levels were measured using an automated system based on the Griess reaction. NOx levels for a 24‐h period reproducibly became lowest at 6 A.M. in restricted healthy volunteers, and became stable in inpatient volunteers at 6 A.M. within 4 days after admission.

Results: Based on these findings, NOx levels at 6 A.M. in inpatients can be considered as the basal levels. In 40 inpatients suspected of CAD (28 men, 12 women; mean age 60 ± 11 years), the basal levels of NOx were not related to CAD and its risk factors, except for hypercholesterolemia. The NOx level of patients with hypercholesterolemia was significantly lower than that of patients with normal cholesterol (n = 16, 34 ± 16 μmol/l vs. n = 24, 49 ± 23 μmol/l, p < 0.03). Furthermore, the NOx levels correlated negatively with the total cholesterol and low‐density lipoprotein cholesterol levels (r= –0.40, p < 0.01; r = –0.47, p < 0.003, respectively), but not with other lipid fraction levels.

Conclusion: The results suggest that the quantity of basal endothelium‐derived NO synthesis may be decreased in the presence of hypercholesterolemia.
Long‐term management of atrial fibrillation
Authors: John Camm A. , Gallagher Mark M. , John Camm A.
Published: February 2009

In the past decade, catheter ablation techniques and implantable devices have revolutionized the treatment of ventricular arrhythmias, junctional arrhythmias, and atrial flutter. For most patients presenting with atrial fibrillation (AF), the treatment available today is similar to that used a century ago, although nonpharmacologic strategies of therapy have begun to emerge for selected cases. There have been important recent advances in our understanding of the pathophysiology of AF and its complications, and it may be possible to improve patient management by refinement of the way in which current drugs are used.
Effects of imidapril therapy on endogenous fibrinolysis in patients with recent myocardial infarction
Authors: Soejima Hirofumi , Ogawa Hisao , Yasue Hirofumi , Suefuji Hisakazu , Kaikita Koichi , Nishiyama Koichi
Published: February 2009

Background: Treatment with an angiotensin‐con verting enzyme (ACE) inhibitor in patients with myocardial infarction has been shown to modify endogenous fibrinolysis.

Hypothesis: We investigated the effects of the ACE inhibitor imidapril on endogenous fibrinolysis in association with the serum ACE activity.

Methods: In a randomized, double‐blind, placebo‐controlled study beginning 4 weeks after uncomplicated myocardial infarction, 15 patients received imidapril (5 mg daily) (imidapril group) and another 15 received placebo therapy (placebo group) for 4 weeks. Blood sampling was performed before the start of administration and on Days 3, 7, and 28 after the start of administration. Serum ACE activity and plasma fibrinolytic variables [plasminogen activator inhibitor (PAI) activity, plasminogen activator inhibitor type 1 (PAI‐1) antigen level, and tissue type plasminogen activator (TPA) antigen level] were measured.

Results: There was no difference between the imidapril and placebo groups in serum ACE activity or plasma fibrinolytic variables before administration. Serum ACE activity decreased significantly on Days 3, 7, and 28 in the imidapril group. The decrease of PAI activity and PAI‐1 antigen levels was significantly less on Days 7 and 28, but not on Day 3. The TPA antigen level in the imidapril group was unchanged. None of the parameters in the placebo group was changed.

Conclusion: The ACE inhibitor imidapril modified fibrinolysis, but the effects occurred after the inhibition of serum ACE activity.
Abnormal Q waves on the admission electrocardiogram of patients with first acute myocardial infarction: Prognostic implications
Authors: Birnbaum Yochai , Sclarovsky Samuel , Zlotikamien Bruria , Herz Izhak , Chetrit Angela , Olmer Liraz , Barbash Gabriel I.
Published: February 2009

Background: Q waves developed in the subacute and persisting into the chronic phase of myocardial infarction (MI) usually signify myocardial necrosis. However, the mechanism and significance of Q waves that appear very early in the course of acute MI (<6 h from onset of symptoms), especially if accompanied by ST elevation, are probably different.

Hypothesis: This study assesses the prognostic implications of abnormal Q waves on admission in 2,370 patients with first acute MI treated with thrombolytic therapy <6 h of onset of symptoms.

Results: Patients with abnormal Q waves in ≥2 leads with ST‐segment elevation (n = 923) were older than patients without early Q waves (n = 1,447) (60.6 ±11.9 vs. 58.8 ±11.9 years, respectively; p = 0.0003), and had a greater incidence of hypertension (34.3 vs. 30.5% p = 0.05) and anterior MI (60.6 vs. 41.1 % p<0.0001). Time from onset of symptoms to therapy was longer in patients with Q waves upon admission (208 ± 196 vs. 183 ± 230 min; p = 0.01). Peak serum creatine kinase (2235 ± 1544 vs. 1622 ± 1536 IU; p<0.0001), prevalence of heart failure during hospitalization (13.8 vs. 7.0%, p<0.0002), hospital mortality (8.0 vs. 4.6% p = 0.02), and cardiac mortality (6.6 vs. 4.5%, p = 0.11) were higher in patients with anterior MI and with abnormal Q waves than in those without abnormal Q waves upon admission. There was no difference in peak creatine kinase, prevalence of heart failure, in‐hospital mortality, and cardiac mortality between patients with and without abnormal Q waves in inferior MI. Multivariate regression analysis confirmed that mortality is independently associated with presence of Q waves on admission (odds ratio 1.61; 95% CI 1.04–2.49; p = 0.04 for all patients; odds ratio 1.65; 95% CI 0.97–2.83; p=0.09 for anterior wall MI.

Conclusion: Abnormal Q waves on the admission electrocardiogram (ECG) are associated with higher peak creatine kinase, higher prevalence of heart failure, and increased mortality in patients with anterior MI. Abnormal Q waves on the admission ECG of patients with inferior MI are not associated with adverse prognosis.
The effect of iron overload in the hearts of patients with beta‐thalassemia
Authors: Brili Stella V. , Castelanos Stamatis S. , Aggeli Constadina J. , Tentolouris Costas A. , Pitsavos Christos E. , Toutouzas Pavlos K. , Tzonou Anastasia I.
Published: February 2009

Background and hypothesis: An important complication of beta‐thalassemia is iron deposition in cardiac tissues resulting in fibrosis and dysfunction. Our aim was the investigation of the possible clinical effect of iron loading in the heart of patients with beta‐thalassemia prior to the appearance of symptoms of depressed systolic function.

Methods: Thirty‐five patients with beta‐thalassemia, of whom 24 had the major type (Group 1) and 11 had the intermedia type (Group 2) were studied. Eleven age‐ and gender‐matched controls were also studied (Group 3). All patients were evaluated echocardiographically and were shown to have normal left ventricular systolic function and dimensions. Serum ferritin, atrial natriuretic peptide (ANP), left atrial diameter (LAD), peak early mitral inflow velocity (E), peak late mitral inflow velocity (A), E/A ratio, deceleration time of the mitral inflow E wave (DT), and isovolumic relaxation time (IVRT) were measured.

Results: Univariate analysis showed that both groups of patients had similarly increased LAD and ANP plasma levels. Group 1 had a higher E/A ratio (2.27 ± 0.88) SS than Group 2 (1.69 ± 0.47, p = 0.05) and Group 3(1.50 ± 0.38, p = 0.01). Serum ferritin was significantly higher in Group 1 (3.526 ± 0.352) than in Group 2 (2.808 ± 0.288, p < 10–5) and Group 3 (2.139 ± 0.124, p<10–5). Multivariate analysis showed that ANP is a factor that is affected by the LAD and E/A ratio and that serum ferritin levels affect the LAD and E/A ratio.

Conclusions: Although LAD and ANP levels are increased in patients with beta‐thalassemia, the increased serum ferritin levels of patients seem to affect left atrial size and E/A ratio. ANP secretion is consecutively affected by these factors.
Left atrial size is the major predictor of cardiac death and overall clinical outcome in patients with dilated cardiomyopathy: A long‐term follow‐up study
Authors: Modena Maria Grazia , Muia Nicola , Sgura Fabio Alfredo , Molinari Rosella , Castelli Annadele , Rossi Rosario
Published: February 2009

Hypothesis: This study was undertaken to determine whether echo‐derived left atrial dimension and other echocardiographic, clinical, and hemodynamic parameters detected at the time of entry into the study may influence prognosis in patients with dilated cardiomyopathy during a long‐term follow‐up.

Methods: This was a prospective cohort analysis of 123 patients with dilated cardiomyopathy. Clinical evaluation, chest x‐ray, M‐mode and two‐dimensional echocardiogram, exercise test, 72‐h ambulatory electrocardiogram monitoring, and cardiac catheterization study were performed in all patients. The study was divided into two phases: in the first phase, patients were divided into two groups according to the left atrial size (≥45 mm; <45 mm), with cardiac death as the end point. In the second phase, all patients were further divided into two groups according to their clinical course. A multivariate analysis was performed to determine independent correlated parameters of cardiac mortality and overall clinical outcome.

Results: Cardiac mortality rate was 47.9%: 29% in the group without left atrial dilation and 54.3% in the group with dilated left atrium. Multivariate analysis revealed that left atrium ≥45 mm, New York Heart Association functional classes III/IV, and the presence of one or more episodes of ventricular tachycardia at Holter monitoring were independent predictors of cardiac mortality, while left atrium ≥45 mm, left ventricular end‐diastolic pressure >17 mmHg, and exercise tolerance ≤ 15 min were independent predictors of poor clinical outcome.

Conclusions: Our results revealed that left atrial size is the principal independent predictor of prognosis in patients with dilated cardiomyopathy in that patients with left atrial dilation had an increase in mortality and a worse clinical outcome compared with those without left atrial dilation.
Antihypertensive effects of mibefradil: A double‐blind comparison with diltiazem CD
Authors: Massie Barry M. , Chrysant Steven G , Jain Adesh , Weir Matthew , Weiss Robert , Kobrin Isaac
Published: February 2009

Background and hypothesis: Mibefradil is the first compound of a new class of calcium antagonists with a unique chemical structure and mechanism of action. This trial compared mibefradil with diltiazem CD, a widely prescribed calcium antagonist for the treatment of hypertension.

Methods: In all, 201 patients with uncomplicated, mild‐to‐moderate essential hypertension with a baseline sitting diastolic blood pressure (SDBP) of ≥95 and ≤ 114 mmHg were evenly randomized to receive either mibefradil (100 mg) or diltiazem CD (360 mg) daily for 12 weeks. To determine whether antihypertensive effects persisted after 12 weeks, patients then entered a 4‐week withdrawal period during which they remained on active treatment or were switched to placebo.

Results: Efficacy variables were the changes from baseline in SDBP to the end of the treatment period (Week 12) and during the randomized withdrawal period (Week 16). At Week 12, the reduction from baseline in SDBP at trough was significantly greater (p<0.001) in the mibefradil group (–14.0 ± 7.8 mmHg) than in the diltiazem CD group (–9.5 ± 7.5 mmHg). Significantly more patients (72%) on mibefradil achieved SDBP normalization by Week 12 than did patients on diltiazem (51%) (p<0.01). Patients maintained on mibefradil or diltiazem CD during the withdrawal period had a significantly larger reduction in trough SDBP at Week 16 than those switched to placebo. The incidence of side effects was similar in both treatment groups.

Conclusions: Once‐daily mibefradil was equally well tolerated as diltiazem CD, but was more effective in lowering blood pressure at the doses studied than the extended‐release formulation of diltiazem.
Myocardial bridging in a young patient with sudden death
Authors: Cutler David , Wallace John M.
Published: February 2009

Systolic compression of a coronary artery is considered to be a benign phenomenon, although numerous case reports have suggested an association between bridging and sudden death or ischemia in certain patients without other abnormalities on cardiovascular evaluation. We present the case of a young patient with two episodes of spontaneous ventricular fibrillation and electrocardiographic evidence of ischemia, whose only primary abnormality on extensive workup was a long segment of left anterior descending systolic compression. This case adds to the growing body of anecdotal evidence that myocardial bridging may be associated with significant cardiac events.
Amiodarone: The expanding antiarrhythmic role and how to follow a patient on chronic therapy
Authors: Singh Bramah N.
Published: February 2009

Amiodarone was introduced as an antiarrhythmic compound in the early 1970s and was approved in the U.S. for the treatment of refractory ventricular arrhythmias in late 1984. Since that time the drug has become the most widely studied antiarrhythmic compound with expanding potential indications, including maintaining stability of sinus rhythm, secondary prevention in the survivors of myocardial infarction, and prolongation of survival in certain subsets of patients with congestive heart failure. Intravenous amiodarone was introduced in the U.S. in 1995 for the control of recurrent destabilizing ventricular tachycardia or ventricular fibrillation resistant to conventional therapy. The level of comfort in its use has risen considerably in the recent past. This has stemmed from the reasonably decisive evidence that class I agents increase mortality in patients with structural heart disease. In contrast, amiodarone either reduces mortality or its effect is neutral; this is consistent with its low to negligible proarrhyfhmic actions. The drug does not aggravate heart failure and it may even increase left ventricular ejection fraction and improve exercise capacity. Above all, it is becoming increasingly evident from wider experience and from controlled clinical trials that the side‐effect profile of the drug is not as compelling an issue as it appeared to be when first used in much higher doses. Therefore, the overall objective of amiodarone therapy is to use the lowest dose that produces a defined therapeutic end point without causing serious side effects. Careful clinical surveillance in conjunction with monitoring of certain laboratory parameters and indices of efficacy at regular intervals permits the drug to be used effectively in a large number of patients who fail to respond to, or are intolerant of other antiarrhythmic compounds. Many experienced clinicians have begun to consider the use of amiodarone as first‐line therapy in certain disorders of rhythm, especially in patients with severely compromised ventricular function.
Circadian rhythmic fractal scaling of heart rate variability in health and coronary artery disease
Authors: Qtsuka Kuniaki , Cornélissen Germaine , Halberg Franz
Published: February 2009

Background: In clinical cardiology, heart rate variability is a putative index of autonomic cardiovascular function. Signs of reduced vagal activity are not only associated with an enhanced risk of sudden cardiac death, but such impaired heart rate variability became a new predictor of sudden cardiac death and other mortality in patients with a variety of diseased states.

Hypothesis: It is postulated (1) that the time structure (chronome) of heart rate variability in clinical health includes a circadian rhythm and deterministic chaos, the latter gauged by the correlation dimension of RR intervals; and (2) that this chronome is altered in patients with coronary artery disease (CAD).

Methods: From 24‐h Holter records of 11 healthy controls and 10 patients with CAD, 500‐s sections around 02:00, 06:00, 10:00, 14:00, 18:00 and 22:00 hours were analyzed for smoothed RR intervals sampled at 4 Hz. Correlation integrals were estimated for embedding dimensions from 1 to 20 with a 1.0‐s time lag, using an algorithm modified from Grassberger and Procaccia. The Wilcoxon signed‐rank test compares circadian end points assessed by cosinor between the CAD patients and age‐matched controls.

Results: A circadian rhythm characterizes the correlation dimension of healthy subjects peaking during the night (p «0.005). Patients with CAD have a lowered correlation dimension (p « 0.05) and an altered circadian variation which requires the consideration of an approximately 12‐h (circasemidian) component.

Conclusion: The results demonstrate the sensitivity of circadian rhythms for the detection of disease. A partial 24‐ to 12‐h (circadian‐to‐circasemidian) frequency multiplication (or partial variance transposition) in CAD of the correlation dimension, apart from being a potential clue to the etiology of the disease, adds a new feature to a chronocardiology combining, with the fractal scaling, an assessment of circadian and circasemidian components as measures of predictable variability to be tested for use in diagnosis, prognosis, and as putative guides to treatment timing.
Atrial fibrillation: A review of mechanism, etiology, and therapy
Authors: Mackstaller Lorraine L. , Alpert Joseph S.
Published: February 2009

The prevalence of elderly individuals in the populations of developed countries is increasing rapidly, and atrial fibrillation (AF) is quite common in these elderly patients: currently, 11% of the U.S. population is between the ages of 65 and 85 years; 70% of people with AF are between the ages of 65 and 85 years. AF causes symptoms secondary to hemodynamic derangements that are the result of increased ventricular response and loss of atrial booster function. AF can lead to reversible impairment of left ventricular function, cardiac chamber dilatation, clinical heart failure, and thromboembolic events. AF requires treatment in order to prevent these potential complications. Type Ia, Ic, and III antiarrhythmics are capable of converting AF to normal sinus rhythm (NSR). Amiodarone has the greatest efficacy and safety for converting AF and maintaining NSR while digoxin and verapamil are ineffective in restoring NSR. Quinidine, flecainide, disopyramide, and sotalol have also been shown to maintain NSR after conversion of AF. Proarrhythmia is a definite concern with the latter four agents. Alternative therapy for AF includes anticoagulation with warfarin or aspirin for the prevention of thromboembolic events, and a variety of agents to control the ventricular response. All medications used to treat AF carry significant risks in the elderly, whether from proarrhythmia, overdosing because of compliance errors, or hemorrhage secondary to anticoagulation. Treatment of AF must be based on a careful risk‐benefit evaluation. The physician must know the capability of the particular patient as well as drug mechanisms and effects in the elderly. The decision to convert patients from AF to NSR or to leave the patient in AF and control the ventricular response represents a complex intellectual challenge. Factors favoring one or the other of these two clinical strategies are discussed. Multicenter clinical trials, for example, the Atrial Fibrillation Follow‐up Investigation Rhythm Management (AFFIRM) trial, are currently underway to assess various clinical strategies for maintenance of NSR following conversion from AF. Amiodarone is one of the drugs under investigation.
Pulmonary hypertension: Newer concepts in diagnosis and management
Authors: Moraes Denzil , Loscalzo Joseph
Published: February 2009

Pulmonary hypertension comprises a family of disorders occurring as a primary disease or as a complication of a large number of respiratory and cardiac diseases. Pulmonary hypertension is present when pulmonary artery pressure or mean pressure exceeds 30 mmHg or 20 mmHg, respectively. Underlying the hemodynamic changes that result in pulmonary hypertension, whether from hypoxia, acidosis, increased pulmonary blood flow, increased shear stress, or idiopathic causes, is a dysfunctional vascular endothelium. In this review, the role of the history and physical examination in the initial assessment is emphasized. Newer diagnostic modalities, such as subselective pulmonary angiography and ultrafast computed tomography scanning, are reviewed. Low‐flow oxygen, anticoagulation, and calcium‐channel blockade are presented as accepted therapeutic modalities. Inhaled nitric oxide and prostacyclin infusion are presented as newer therapies that may be useful given the limited availability of donor organs for heart‐lung transplantation. Future therapeutic strategies are likely to develop from advances in vascular biology.
What can we learn from exercise testing beyond the detection of myocardial ischemia?
Authors: Weber Karl T.
Published: February 2009

Noninvasive cardiopulmonary exercise (CPX) testing has proven useful in the assessment of heart and lung disease, including cardiac and ventilatory reserves. CPX includes the monitoring of respiratory gas exchange, O2 uptake and CO2 production, together with minute ventilation and its components—tidal volume and respiratory rate—together with surveillance of electrocardiography and blood pressure during supervised, incremental exercise. Exercise responses in anaerobic threshold and/or maximal O2 uptake are used to grade functional capacity objectively and to predict cardiac reserve (exercise cardiac output), which grades the severity of chronic cardiac or circulatory failure. CPX also serves to distinguish primary cardiac from ventilatory‐based exertional dyspnea.
Reverse remodeling in heart failure with intensification of vasodilator therapy
Authors: Levine T. Barry , Levine Arlene B. , Keteyian Steven J. , Narins Barbara , Lesch Michael
Published: February 2009

Background: Heart failure therapy with beta‐receptor blockade has been shown to effect a partial reversal of left ventricular (LV) remodeling in heart failure.

Hypothesis: We tested the hypothesis that, in the absence of beta blockade, uptitration of angiotensin‐converting enzyme (ACE) inhibitor and nitrate therapy over conventional dosages would improve symptoms as well as LV function in patients with severe heart failure.

Methods: For patients with nonischemic or ischemic cardiomyopathy, intensive high‐dose angiotensin‐converting enzyme inhibitor and nitrate therapy was uptitrated. Echocardiograms were obtained semiannually and evaluated in a blinded fashion. Of 99 patients in the study, aged 55 ± 13 years, with heart failure for 5.2 ± 3.1 years, 74 were men, 69 were Caucasian, and 34 had ischemic cardiomyopathy. The final dosage of enalapril was 40 ± 23 mg/day and of isosorbide dinitrate it was 153 ±127 mg/day.

Results: Initial New York Heart Association classification improved from 2.8 ± 0.9 to 1.7 ± 0.9 (p<0.001) in 2.7 years of follow‐up. Of the 99 patients, 72 further improved their ejection fraction. For the whole group, ejection fraction increased from 21 ± 9% to 30 ± 13% in 6 months (p>0.001), with are‐duction in LV end‐diastolic size from 6.6 ± 0.9 to 6.3 ± 1.0 cm (p = 0.002), and a decrease in the severity of mitral regurgitation from mild/moderate to only mild. Resting heart rate declined with no change over time in systemic systolic blood pressure. Final ejection fraction for nonischemic patients (n = 65) was 36 ± 16% versus 23 ± 9% for the ischemic population.

Conclusion: Uptitration of high‐dose ACE inhibitor and nitrate therapy to higher doses is well tolerated in severe heart failure, further improves both clinical status and LV systolic function, and is more effective in nonischemic than in ischemic cardiomyopathy.
Nitric oxide and cardiac failure
Authors: Ikeda Uichi , Shimada Kazuyuki
Published: February 2009

Cardiac myocytes express two types of nitric oxide (NO) synthase, eNOS and iNOS. eNOS activity is regulated by the contractile state of the heart, while iNOS expression is induced by cytokines. Nitric oxide induced by cytokines causes negative inotropic and lethal effects on cardiac myocytes. Expression of iNOS in the myocardium is increased in patients with dilated cardiomyopathy with clinical evidence of heart failure. Several neurohumoral factors activated in chronic heart failure augment cardiac iNOS expression and could cause cardiac dysfunction and cell damage.
Nonneoplastic diseases of aorta and pulmonary trunk—Part iv
Authors: Waller Bruce , Waller Bruce F. , Clary James D. , Rohr Todd
Published: February 2009

This five‐part review focuses on selected nonneoplastic diseases of the aorta and pulmonary trunk. Because many more diseases affect the aorta compared with the pulmonary trunk and right and left main pulmonary arteries, most of this review will be devoted to disorders of the aorta. Part IV of the series discusses cystic medial degeneration, trauma, and congenital diseases of the aorta.
Hemodynamic action of captopril in coronary patients with heart failure tolerant to nitroglycerin
Authors: Störk Thomas , Eichstädt Hermann , Möckel Martin , Gareis Ragnar , Bodemann Thomas , Möller Reinhold
Published: February 2009

Background:At present there is little dispute that clinical tolerance of organic nitrates occurs during long‐term treatment of patients with stable angina pectoris and congestive heart failure.

Hypothesis:Captopril exerts a favorable hemodynamic effect in coronary patients with heart failure who are clinically tolerant to nitroglycerin.

Methods: Development of nitrate tolerance was observed during intravenous nitroglycerin treatment (10 mg/h) in 16 of 19 patients (7 women, 12 men; mean age 56 ± 8 years) with coronary heart disease [stenosis ≥ 75%, New York Heart Association (NYHA) classes II–III). The criterion applied was a loss of efficacy of at least 50% with regard to mean pulmonary capillary wedge pressure compared with the maximum effect of nitrate. The effect of captopril (50 mg p.o.) was determined in a blank test. Captopril (50 mg p.o.) was administered again at the stage of clinically manifest nitrate tolerance.

Results:Compared with the effect of captopril alone, significantly more pronounced reductions in mean pulmonary capillary wedge pressure (33% compared with 27%) and in mean pulmonary arterial pressure (36% compared with 17%) and significantly greater increases in cardiac index (14% compared with 7%) and stroke work index (34% compared with 18%) (p < 0.05 in each case; Wilcoxon test for linked random samples) were measured. Maintaining nitroglycerin infusion, the effect of captopril (at least 90% of the maximum effect) lasted for 123 ± 24 min. The baseline values (at least 75% decline in the effect of captopril) were only reached after 369 ± 34 min.

Conclusion:The results document a favorable hemodynamic effect of captopril in nitrate tolerance which is significantly better than that of captopril alone.
Increased adhesiveness of white blood cells in patients with unstable angina: Additional evidence for an involvement of the immune‐inflammatory system
Authors: Leibovitz Eyal , Hertz Yizhak , Liberman Eliezer , Sclarovsky Samuel , Berliner A.S.
Published: February 2009

Background: Data are being accumulated on the presence of inflammatory response in patients with acute coronary syndromes.

Hypothesis: The study was undertaken to confirm that the adhesive state of the peripheral blood leukocytes can provide information on an inflammatory process in patients with unstable angina pectoris.

Methods: The study included 21 patients with unstable angina, 32 patients with stable angina, and 13 patients with chest pain and no evidence of coronary artery disease.

Results: The percentage of aggregated leukocytes in patients with unstable angina (5.8 ± 3.2%) was significantly (p < 0.02) increased compared with that of patients with no evidence of active coronary disease (3.2 ± 2.6%).

Conclusion: Additional evidence for an existing smoldering inflammatory process in unstable angina pectoris can be provided by testing the percentage of aggregated leukocytes in peripheral blood.
Nonneoplastic diseases of aorta and pulmonary trunk—Part V
Authors: Waller Bruce F. , Clary James D. , Rohr Todd
Published: February 2009

This five‐part review focuses on selected nonneoplastic diseases of the aorta and pulmonary trunk. Because many more diseases affect the aorta compared with the pulmonary trunk and the right and left main pulmonary arteries, most of this review will be devoted to disorders of the aorta. Part V of this five‐part series on diseases of the aorta and the pulmonary trunk focuses on nonneoplastic diseases of the pulmonary trunk and the right and left main pulmonary arteries.
The Importance of lowering cholesterol in patients with coronary heart disease
Authors: Eisenberg Daniel
Published: February 2009

Patients with prior manifestations of cardiovascular disease account for about 50% of all myocardial infarctions and 70% of deaths due to coronary disease. The benefits of lowering elevated cholesterol levels in patients with coronary disease are well documented. Recent clinical trials indicate that these benefits, in terms of reduced risk of cardiovascular morbidity and mortality, extend even to patients with “average” cholesterol levels and support the importance of reaching a target low‐density lipoprotein cholesterol level of ≤ 100 mg/dl. These findings argue in favor of attaining and maintaining optimal lipid targets for secondary (and primary) prevention of atherosclerotic vascular disease in patients at risk.
Colchicine for large pericardial effusion
Authors: Adler Yehuda , Finkelstein Yaron , Assali Abid , Guindo Josep , Bayes‐Genis Antoni , Luna Antony Bayes De , Khouri Asaad
Published: February 2009

On the basis of our reported experience with colchicine for recurrent pericarditis, we administered colchicine to two patients with large pericardial effusions complicating idiopathic pericarditis. The first was a 26‐year‐old male who showed clinical deterioration following emergency pericardiocentesis and aspirin (3 g/day) for 10 days; the second was a 2‐year‐old girl who was unsuccessfully treated with aspirin (100 mg/kg/day) for 2 weeks, followed by corti‐costeroids for 7 months. Administration of colchicine (1 mg/ day) instead of aspirin in the first case, and with a rapid tapering‐off of the corticosteroids in the second case, led to complete regression of the pericardial effusion on echocardiography within 1 week and 1 month, respectively. Colchicine was discontinued after 1 month in the first patient and was continued for 6 months in the child. Neither has had a recurrence at 24 and 6 months of follow‐up, respectively. No side effects of colchicine were observed. We conclude that colchicine may be effective in the treatment of large pericardial effusion when therapy with nonsteroidal anti‐inflammatory drugs and/or corticosteroids fails.