Kazuhiko Misu

Echocardiographic prediction of left ventricular dysfunction after mitral valve repair for mitral regurgitation as an indicator to decide the optimal timing of repair

OBJECTIVES This study sought to determine whether echocardiography before mitral valve repair (MVR) for mitral regurgitation (MR) was predictive of postoperative left ventricular (LV) dysfunction and useful for deciding the optimal timing of repair. BACKGROUND Some reports have shown that the preoperative echocardiographic data of left ventricular ejection fraction (LVEF) and left ventricular end-systolic diameter (LVDs) were good predictors of postoperative LV dysfunction. However, few reports were based on long-term follow-up data of large numbers of patients who underwent MVR in the last decade. METHODS A total of 274 patients with moderate or severe MR underwent MVR between October 1, 1991, and September 30, 2000. Among them, 171 patients who had both an operation for isolated MR due to degenerative pathology and a postoperative echocardiogram were studied. Postoperative echocardiograms were performed 3.9 +/- 2.4 years after the operation. The LVEF decreased from 66 +/- 10% before surgery to 63 +/- 11% after surgery (p < 0.0001). On univariate analysis, preoperative LVEF and LVDs correlated with postoperative LVEF (r = 0.41 and r = -0.39, respectively). Overall, postoperative LV dysfunction (defined as LVEF <50%) was not frequent (12%). However, the incidence of postoperative LV dysfunction was high in patients with preoperative LVEF <55% (38%) or LVDs > or =40 mm (23%). CONCLUSIONS In patients with MR, the echocardiographic data of LVEF and LVDs were good predictors of postoperative LV dysfunction. When a decrease in LVEF or an increase in LVDs is detected, MVR should be considered to preserve postoperative LV function.

Diagnostic Implications of Elevated Levels of Smooth-Muscle Myosin Heavy-Chain Protein in Acute Aortic Dissection: The Smooth Muscle Myosin Heavy Chain Study

Aortic dissection is an uncommon acute disease associated with high mortality and morbidity (1, 2). Initial management has a critical effect on survival. While diagnosis and treatment of the disease have greatly improved in recent years as a result of newer diagnostic (3) and therapeutic (4, 5) techniques, it is still difficult to recognize at clinical presentation (6). To aid in the initial diagnostic screening, an assay of circulating smooth-muscle myosin heavy-chain protein, a protein specific to smooth muscle that is released from damaged aortic medial smooth muscle at the onset of aortic dissection, was developed (7). Biochemical diagnosis of acute aortic dissection is attractive because it is rapid, noninvasive, and relatively easy to perform. A rapid 30-minute assay was developed for clinical use after initial studies that used an experimental assay showed promising results (8-10). Our study addressed the sensitivity and specificity of the rapid assay in acute aortic dissection. Methods The enzyme immunoassay of smooth-muscle myosin heavy-chain protein was developed with antibodies and reactions optimized for sensitive detection and minimal performance time (30 minutes). Cross-reactivity against aortic and uterine myosin was 100%; in contrast, cardiac and skeletal muscle showed cross-reactivity less than 0.05%. The measuring range of the assay was approximately 1.6 to 100 g/L. Within-run and between-run reproducibilities as measures of analytical precision were 6.2% 1.3% and 3.2% 1.4 %, respectively (coefficient of variance). Recovery as a measure of analytical accuracy (defined as the observed vs. the expected value when purified human smooth-muscle myosin heavy-chain protein was added to patient serum) was 93.9% 10.0%. All assays were performed by the diagnostics division of Yamasa Corp. (Tokyo, Japan). The technical specifications and details of the assay are available from the authors. We included patients with acute aortic dissection who presented to participating centers between August 1996 and March 1999. Eight major cardiovascular centers were selected for participation in the Smooth Muscle Myosin Heavy Chain Study because they had a large volume of early admissions for acute aortic dissection. Included patients had aortic dissection within 24 hours of onset of symptoms; the diagnosis was confirmed by imaging. Traumatic aortic dissections were excluded. Each center approved the study protocols, and patient consent was obtained. Single-specimen blood sampling was done at initial presentation. Protocols for documenting clinical characteristics, including age, sex, time of onset, time of admission, diagnosis, lesion site (according to DeBakey classification), and time of blood sampling, have been described elsewhere (9). We included 131 healthy volunteers presenting for an annual health examination as normal controls; we also included 48 patients with acute myocardial infarction to determine the specificity of the assay in distinguishing aortic dissection from other diseases that present with chest pain. We analyzed receiver-operating characteristic (ROC) curves to show sensitivity and specificity. Results are presented as the mean SD. Statistical analysis was done by using commercially available software (StatView 4.0, Abacus Systems, Berkeley, California). MannWhitney U tests were used for two-group comparisons. A P value less than 0.05 was considered statistically significant. Analysis for differences across time or between healthy volunteers and patients with aortic dissection are conservative because they do not adjust for differences among centers. Results We enrolled 95 consecutive patients with aortic dissection (58 men, 37 women; mean age, 64.7 13.1 years) within the first 24 hours after onset of symptoms. This sample of predominantly male patients, ranging from middle-aged to elderly, is typical for aortic dissection. In all cases, diagnosis was confirmed by imaging. Thirty-three patients had DeBakey type I lesions, 12 had DeBakey type II lesions, and 50 had DeBakey type III lesions. Patients presented 5.9 5.9 hours after symptom onset. Of importance, 35% of patients presented within 3 hours after onset and 65% presented within 6 hours after onset. Sensitivity and Specificity We compared serum levels of smooth-muscle myosin heavy-chain protein in patients with acute aortic dissection and 131 healthy volunteers (35 men, 13 women; mean age, 65.9 11.9 years). Values were significantly higher in patients with acute aortic dissection (22.4 40.4 g/L vs. 0.9 0.4 g/L, respectively; P <0.001). The highest levels (51.0 52.3 g/L) were seen in the 33 patients who presented within 3 hours after onset. Levels decreased significantly to 11.5 28.5 g/L in 29 patients in the next 3 hours (P <0.001) and decreased further to 3.3 5.2 g/L in 33 patients thereafter. During the initial 3 hours after symptom onset, sensitivity was 90.9% (95% CI, 85% to 96.8%) at a cutoff level of 2.5 g/L (the upper limit of the normal population) (Figure 1, top). Sensitivity decreased to 72.4% (CI, 65.3% to 79.5%) in the following 3 hours and decreased to 30.3% (CI, 23.9% to 36.7%) thereafter. The assay had a specificity of 98% and a diagnostic accuracy of 96% at the cutoff level of 2.5 g/L in patients with aortic dissection compared with healthy volunteers (Figure 1, bottom). Figure 1. Sensitivity and specificity of the smooth-muscle myosin heavy-chain assay. Top. Bottom. solid line dotted line To determine the specificity of the assay in distinguishing aortic dissection from diseases that present with similar symptoms, such as chest pain, we examined levels of smooth-muscle myosin heavy-chain protein in 48 patients with acute myocardial infarction who presented within 3 hours after onset (35 men, 13 women; mean age, 65.9 11.9 years). In these patients, the serum level of smooth-muscle myosin heavy-chain protein was 2.1 1.6 g/L (P <0.001 compared with acute aortic dissection). The assay had a specificity of 83% at the cutoff level of 2.5 g/L in patients with acute myocardial infarction (Figure 1, bottom). On the basis of these data, 2.5 g/L was set as the clinical decision limit because analysis of the ROC curve showed favorable sensitivity and specificity compared with normal volunteers and patients with acute myocardial infarction. Levels of smooth-muscle myosin heavy-chain protein that exceeded 10 g/L showed 100% specificity for aortic dissection. Analysis according to Type of Aortic Dissection In the first 3 hours after onset, all patients who had proximal lesions that were classified as DeBakey type I or II also had levels of smooth-muscle myosin heavy-chain protein that exceeded the clinical decision limit of 2.5 g/L. Conversely, patients who presented with definitive aortic dissection within the first 3 hours after onset and had levels of smooth-muscle myosin heavy-chain protein less than 2.5 g/L had distal lesions that were classified as DeBakey type III. Levels of smooth-muscle myosin heavy-chain protein were probably lower in patients with distal lesions because the abdominal aorta has less smooth muscle than the thoracic aorta. Analysis of samples taken within 3 hours of symptom onset confirmed that levels of smooth-muscle myosin heavy-chain protein were significantly higher in proximal lesions than in distal lesions (71.4 59.5 g/L vs. 31.8 36.7 g/L, respectively; P =0.03). The assay had superior sensitivity for proximal lesions 3 to 6 hours after onset and thereafter, which was confirmed by analysis of the ROC curve (Figure 2). Thirty-three patients, 16 of whom had proximal lesions, were tested within 3 hours after symptom onset. Figure 2. Levels of smooth-muscle myosin heavy-chain protein according to type of aortic dissection. Top. solid line dotted line Bottom. Discussion We found that the rapid assay of smooth-muscle myosin heavy-chain protein had a high sensitivity (90.9%) and acceptable specificity (98% compared with healthy controls, 83% compared with patients who had acute myocardial infarction) in patients with aortic dissection who presented within the first 3 hours after symptom onset. The assay performed best in patients with proximal lesions and was less sensitive in patients who presented at a later point in the disease and had decreased levels of smooth-muscle myosin heavy-chain protein. The sensitivity and specificity of this assay in the first 3 hours after onset are similar if not superior to those of transthoracic echocardiography (sensitivity, 59% to 85%; specificity, 63% to 96%) (11), conventional computed tomography (sensitivity, 83% to 94%; specificity, 87% to 100%) (3, 12), or aortography (sensitivity, 88%; specificity, 94%) (12). However, the assays sensitivity and specificity were lower than those of transesophageal echocardiography (sensitivity, 98% to 99%; specificity, 77% to 97%) (3, 12), helical computed tomography (both almost 100%) (13), or magnetic resonance imaging (both 98%) (14, 15). Because this assay is the first available biochemical diagnostic tool for aortic dissection, it is important to note that comparison with these established diagnostic methods (all of which are imaging procedures) provides only an estimate of its performance. Another important point is that biochemical testing can be done at a fraction of the cost of computed tomography or magnetic resonance imaging (approximately 10%) and is similar in cost to measuring cardiac enzymes (for example, myoglobin or troponin) (16, 17). The cost of a relatively inexpensive blood test is likely to outweigh the small risk for overlooking or failing to exclude the diagnosis of aortic dissection. In addition, manual or automated measurements can be performed easily in a manner similar to that of other conventional enzyme immunoassays. Important issues surround the practicality of this assay in clinical settings. This biochemical test would be most useful at the initial decision-making stage (triaging) in the emergency departm

Delayed enhancement cardiovascular magnetic resonance as a novel technique to predict cardiac events in dilated cardiomyopathy patients

PURPOSE Delayed enhancement cardiovascular magnetic resonance (DE-CMR) can detect cardiac scarring and has the potential to visualize the progression of myocardial remodeling. We determined whether DE-CMR can predict cardiac events in dilated cardiomyopathy patients. MATERIALS AND METHODS Transthoracic echocardiography, coronary arteriography, and DE-CMR studies were performed in 60 consecutive dilated cardiomyopathy (DCM) patients. Percent delayed enhancement (%DE) was determined as the ratio of the area showing delayed enhancement to the total myocardial area in three short-axis views. Patients were classified as advanced group (Group A) when %DE was 10% or higher, and as non-advanced group (Group NA) when %DE was less than 10%. The incidence of cardiac events and the clinical history were compared between Group A and Group NA. RESULTS There were 11 patients in Group A and 49 patients in Group NA. The incidence of cardiac events was significantly higher in Group A (36%; 4/11 patients) than in Group NA (2.0%; 1/49 patients) (log rank, p=0.0001). CONCLUSION DE-CMR is a useful tool to predict cardiac events in DCM patients.

Congestive Heart Failure Caused by Digitalis Toxicity in an Elderly Man Taking a Licorice-Containing Chinese Herbal Laxative

Accessible online at: www.karger.com/crd Dear Sir, Licorice (the root of Glycyrrhiza glabra) has beneficial anti-inflammatory, anti-allergic, gastro-protective and anti-carcinogenic actions [1]. Further, licorice-containing Chinese herbal laxatives have been used in the elderly because of age-related attenuation of bowel movement. However excessive intake of licorice may be a cause for exogenously induced hypertension, hypokalemia, hypernatremia, or suppression of the renin-aldosterone system [2–5]. When combined with digitalis, toxicity could be induced by drug interaction via licorice-associated electrolyte imbalance, particularly in the elderly. An 84-year-old man had mitral regurgitation with atrial fibrillation. The patient had been treated with furosemide 80 mg and digoxin 0.125 mg daily (plasma level of digoxin 1.0 ng/ml). On December 30, 1999, the patient complained of constipation and took a Chinese herbal laxative containing licorice (kanzo) 400 mg and rhubarb (daio) 1,600 mg, three times a day for 7 days. On January 4, 2000, he complained of fatigue, appetite loss and edema in the lower extremities. Physical examination on admission revealed distended jugular veins and a palpable liver. Blood pressure was 120/60 mm Hg and pulse rate was 30 beats per minute. A chest radiograph showed an enlarged cardiac silhouette with lung congestion. Arterial blood gas analysis revealed a partial arterial oxygen pressure of 59 mm Hg, a carbon dioxide pressure of 47 mm Hg and an arterial oxygen saturation of 79%. The plasma level of B-type natriuretic peptide (BNP) was 529 pg/ml, potassium was 2.9 mEq/l, sodium was 139 mEq/l, chloride was 95 mEq/l and digoxin was 2.9 ng/ml. Plasma renin activity was 0.3 ng/ml/h (normal 0.3–2.9 ng/ml/h) and aldosterone was subnormal at 3.8 ng/dl (normal 3.6–24 ng/dl). Eighteen days after stopping both digoxin and the Chinese herbal laxative, his pulse rate recovered to 60 beats per minute along with a relief of heart failure. Subsequently, plasma digoxin was 0.6 ng/ml, potassium was 4.3 mEq/l, renin activity was 1.0 ng/ml/h and aldosterone was 12 ng/dl. The mineralocorticoid activity of licorice was first reported by Molhuysen et al. [6] in 1950. Pharmacologically, glycyrrhizic acid, a component of licorice, inhibits renal 11ßhydroxysteroid dehydrogenase, resulting in the suppression of the conversion of cortisol to cortisone. Cortisol has actions on the renal collecting ducts, which increase the kidney’s exposure to the effects of mineralocorticoids [2, 3]. Recently, licorice products, triterpenoids such as glycyrrhizin, polyphenols and polysaccharides, have been often used as flavoring and sweetening agents in food products [4]. However, prolonged or a daily dose of more than 1,000 mg of licorice may cause pseudo-hyperaldosteronism [5]. The elderly are at an increased risk of digitalis toxicity [7–10]. When combined with Chinese herbal laxatives, digitalis intolerance via licorice-induced pseudo-aldosteronism is often enhanced. This may occur because, (1) the elderly has an age-related decline in renal function and a decrease in the volume of digitalis distribution; (2) the presence of cardiovascular or chronic obstructive pulmonary disease in the elderly also heightens susceptibility to digitalis toxicity, and (3) electrolyte imbalances, such as hypokalemia and hypomagnesemia result from the combined use of other medicines, the most common of which are diuretics. Heart failure or tachycardiac arrhythmias that benefit from the use of digoxin are more prevalent with age. Clinicians should be aware of the potential effects of the combined use of Chinese herbal laxatives and digitalis in the elderly.

Late stent malapposition with marked positive vascular remodeling observed only at the site of drug-eluting stents after multivessel coronary stenting

A 74-year-old woman presented with effort-induced chest pain. Diagnostic coronary angiography revealed three-vessel disease. A successful angioplasty was performed with two sirolimus-eluting stents placed in the left anterior descending artery (LAD) and left circumflex artery (LCX). The right coronary artery (RCA) was treated with a bare-metal stent. Follow-up angiography and intravascular ultrasound (IVUS) assessment were performed 8 months later, which showed late stent malapposition (LSM) with marked positive vascular remodeling around the drug-eluting stents (DES) in both LAD and LCX lesions, but there was no evidence of ectatic area around the BMS in the RCA lesion. Compared with the baseline IVUS, a significant increase in external elastic membrane (EEM) cross-sectional area was found. Twenty-seven months later, we performed repeat follow-up angiography. Intravascular ultrasound still showed vessel malapposition. A previous report showed that aneurysmal dilatation of the stented segment with severe localized hypersensitivity reaction could be a potential cause of late thrombosis after DES implantation. If LSM is related to hypersensitivity of the DES, it may have a potential risk of adverse events. Although there is a paucity of data regarding malapposition as the cause of adverse events, careful long-term follow-up of patients with vessel enlargement after DES placement is recommended.

Etiology of aortic valve disease and recent changes in Japan:a study of 600 valve replacement cases

BACKGROUND Recent studies on the etiology of aortic valve disease in the US showed a decrease in rheumatic valve disease and an increase in age-related degenerative disease. The purpose of this study was to describe the etiology of aortic valve disease and its temporal changes in Japan, based on a large number of cases. METHODS The medical charts of all patients who underwent aortic valve replacement at our institute between 1977 and 1999 were reviewed. Among the 600 patients analyzed, 213 (36%) had pure aortic stenosis, 265 (44%) had pure aortic regurgitation, and 122 (20%) had combined stenosis and regurgitation. RESULTS The causes were rheumatic change (49%), degenerative change (19%), bicuspid valves (18%), infective endocarditis (5%) and others (9%). Rheumatic disease continued to be the most common cause of aortic stenosis, but its frequency decreased from 100% in 1977-1979 to 37% in 1995-1999. In contrast, the frequency of degenerative change among stenotic valves increased recently from 11% in 1990-1994 to 30% in 1995-1999. Similarly, rheumatic disease remained to be the leading cause of aortic regurgitation, with a decline in frequency from 46% in 1985-1989 to 27% in 1995-1999. The percentage of degenerative change among regurgitant valves did not change appreciably. CONCLUSIONS There was a shift in the causes of aortic valve disease, with a decrease in rheumatic disease and an increase in degenerative disease. This trend was similar to that observed in the US. These findings suggest the increasing importance of aortic valve disease due to degenerative change.