Yasuchika Kato

Histologic diagnostic rate of cardiac sarcoidosis: Evaluation of endomyocardial biopsies

BACKGROUND An early diagnosis of cardiac sarcoidosis is important, particularly when considering the need for administering corticosteroid therapy. However, no reports are available on the success rate of diagnosis on the basis of biopsy findings in patients with cardiac sarcoidosis. This study investigated the diagnostic success rate of histologic evaluation of endomyocardial biopsy specimens in patients with this disease. METHODS AND RESULTS Right ventricular endomyocardial biopsy was performed in 26 patients in whom cardiac sarcoidosis was strongly suspected according to the Diagnostic Criteria of Sarcoidosis, plus abnormalities on the electrocardiogram, cardiac radionuclide images, or in left ventricular wall motion. A mean of 4.0 sites were sampled per patient. In each case we determined whether a definitive diagnosis of cardiac sarcoidosis could be made histologically. Noncaseating granulomas were found in only 5 (19.2%) of the 26 cases, thus permitting a histologic diagnosis of cardiac sarcoidosis. A histologic diagnosis was made in 4 (36.4%) of 11 patients who exhibited a dilated cardiomyopathy-like clinical picture, in contrast to only 1 (6.7%) of 15 patients in whom conduction disturbances were the major clinical feature and whose left ventricular ejection fraction was within normal limits. CONCLUSIONS The diagnostic rate achieved with biopsy in cardiac sarcoidosis is low; the patients with sarcoidosis and evidence of significant cardiac involvement should be treated for cardiac sarcoidosis despite negative myocardial biopsies for this disease.

Diagnostic utility of tenascin‐C for evaluation of the activity of human acute myocarditis

Tenascin‐C (TN‐C) is an extracellular matrix protein that is expressed transiently in close association with tissue remodelling in various body sites. In the heart, TN‐C is only present during early stages of development, is not expressed in the normal adult, but reappears in pathological states. The purpose of this study was to analyse the expression of TN‐C in myocardial tissue from myocarditis patients, and to evaluate the diagnostic value of immunostaining for TN‐C in the assessment of inflammatory activity in biopsy specimens. A total of 113 biopsy specimens obtained from 32 patients with a clinical diagnosis of acute myocarditis were examined by immunohistochemistry and in situ hybridization for TN‐C. The immunostaining was semi‐quantified and compared with histological diagnosis according to the Dallas criteria. Furthermore, serial biopsies from 22 patients were taken during convalescence, and sequential changes in TN‐C levels were analysed. Expression of TN‐C was specifically detected in endomyocardial biopsy specimens from patients with active‐stage inflammation, and disappeared in healed stages. The degree of expression of TN‐C correlated with the severity of histological lesions. These data suggest that TN‐C reflects disease activity in cases of human myocarditis. Immunostaining for TN‐C could enhance the sensitivity and accuracy of diagnosis using biopsy specimens. Copyright

Changes in the peripheral eosinophil count in patients with acute eosinophilic myocarditis

In many cases, the diagnosis of eosinophilic myocarditis is suggested by an elevated peripheral blood eosinophil count. However, no detailed studies have been performed on the sequential changes in the initial peripheral blood eosinophil count over the course of the disease. We measured the peripheral blood eosinophil count at the time of presentation in eight patients with eosinophilic myocarditis proven by endomyocardial biopsy and intermittently thereafter. The eosinophil count at the time of onset was ≪500/mm3 in four patients, ≫500/mm3 but ≪1 000/mm3 in three patients, and ≧1 000/mm3 in one patient. In three of the four patients with an initial eosinophil count of ≪500/mm3, an increase to ≧500/mm3 occurred 7–12 days after the onset. The remaining patient did not develop peripheral eosinophilia. In conclusion, in the early stage of eosinophilic myocarditis, peripheral hypereosinophilia is not present initially in some patients, and may not develop during the course of the illness in a subset of these patients.

Angiotensin converting enzyme 2 gene expression increased compensatory for left ventricular remodeling in patients with end-stage heart failure

It has been reported that angiotensin converting enzyme (ACE) 2, a homologue of ACE, has direct effects on cardiac function. However, the role of ACE2 in the development of human heart failure is not fully understood. We evaluated the expression of the ACE2 gene by means of real-time RT-PCR in myocardium from 14 patients with end-stage heart failure. The amount of ACE2 mRNA positively correlated with left ventricular (LV) end-diastolic diameter (r(2)=0.56, p<0.01) but did not significantly correlate with LV ejection fraction or plasma brain natriuretic peptide levels. In conclusion, our data show that the up-regulation of the ACE2 gene in the LV myocardium of patients with severe heart failure was associated with the degree of LV dilatation and may thereby constitute an important adaptive mechanism to retard the progression of adverse LV remodeling.

Efficacy of Atorvastatin Therapy in Ischaemic Heart Disease – Effects on Oxidized Low-density Lipoprotein and Adiponectin

The lipid-lowering and anti-atherosclerotic effects of atorvastatin (10 mg/day) were investigated by measuring changes in the levels of oxidized low-density lipoprotein (LDL), serum lipids (total cholesterol [TC], LDL-cholesterol [LDL-C] and triglycerides [TG]), and in the protein adiponectin. This was undertaken in 22 patients with ischaemic heart disease and serum LDL-C levels > 100 mg/dl. After 3 months of therapy, atorvastatin significantly decreased serum lipids, oxidized LDL was reduced from 457.0 ± 148.6 to 286.9 ± 88.5 nmol/l, and adiponectin increased from 9.7 ± 7.4 to 13.9 ± 9.98 μg/ml. No significant correlation was observed between adiponectin and LDL-C, TG and high-density lipoprotein cholesterol. Atorvastatin therapy was not associated with side-effects, such as myalgia and gastrointestinal disorders, and did not give abnormal laboratory test results. It is concluded that atorvastatin decreases serum lipid and oxidized LDL levels, and increases adiponectin levels in patients with ischaemic heart disease.

Role of myocardial interstitial edema in conduction disturbances in acute myocarditis

The presence of myocardial interstitial edema in acute myocarditis (AM) leads to thickening of the ventricular wall, and conduction disturbances, such as complete atrioventricular block (CAV), also frequently develop. This study was undertaken in order to clarify the relationship between conduction disturbances and myocardial interstitial edema in AM. The subjects comprised 50 patients with acute lymphocytic myocarditis. Based on the results of echocardiographic examinations during the acute stage, the patients were divided into a hypertrophy group (n = 29) in which the sum of the thickness of the interventricular septum and left ventricular (LV) posterior wall was ≥24 mm, and a non-hypertrophy group (n = 21) in which the sum of these parameters was <24 mm. Right ventricular endomyocardial biopsies were performed in the acute stage and the degree of interstitial edema was scored histologically. Left ventricular wall thickness and QRS duration in the acute stage were 27.7 ± 3.6 mm and 124.1 ± 29.6 ms, respectively, in the hypertrophy group, and 19.9 ± 2.4 mm (P < 0.001) and 98.6 ± 21.7 ms (P < 0.01) in the non-hypertrophy group. Complete atrioventricular block was found in 13 of 29 cases (45%) in the hypertrophy group and two of 21 cases (10%) in the non-hypertrophy group (P < 0.01). Myocardial interstitial edema was scored at 1.3 ± 0.8 points in the hypertrophy group and 0.8 ± 0.6 points in the non-hypertrophy group (P < 0.05). Left ventricular wall thickness and QRS duration in the convalescent stage decreased to 21.1 ± 2.6 mm (P < 0.0001) and 97.1 ± 17.4 ms (P < 0.01) in the hypertrophy group, respectively. Only one case (4%) in the hypertrophy group continued to show CAV during the convalescent stage (P < 0.05). The results of this study suggest that myocardial interstitial edema is implicated in the conduction disturbances that occur in AM.

Cardio-renal interaction: impact of renal function and anemia on the outcome of chronic heart failure

The purpose of this study is to investigate the effects of renal function and anemia on the outcome of chronic heart failure (CHF). We targeted 711 consecutive patients who were hospitalized at the Division of Cardiology of Fujita Health University Hospital during a 5-year period. The subjects were divided into four groups according to their estimated glomerular filtration rate (e-GFR) calculated using the Modification of Diet in Renal Disease (MDRD) formula. Intergroup comparisons were conducted for underlying heart diseases, clinical findings at the time of hospitalization, treatment, and outcome. Moreover, the patients were divided into two groups according to their serum hemoglobin concentration at the time of hospitalization, using 12.0 g/dl as the dividing point, to study the effects of anemia on the outcome. In the group with decreased renal function, the average age was higher, and ischemic heart disease and associated conditions such as hypertension and diabetes mellitus were observed in most of the patients. In addition, the rate of anemia development and the plasma B-type natriuretic peptide concentration were also high. The greater the deterioration in renal function, the poorer the outcome became (P < 0.0001). Chronic heart failure complicated by anemia showed an especially poor outcome (P < 0.0001). As this study showed that renal function and anemia significantly affected the outcome of CHF, it is clear that the preservation of renal function and the management of anemia are important in addition to the conventional treatments for CHF.

Successful high-dose intravenous immunoglobulin therapy for a patient with fulminant myocarditis.

A 45-year-old man developed fulminant myocarditis for which ventricular assist devices (intra-aortic balloon pumping and percutaneous cardiopulmonary support) were required for hemodynamic support. Echocardiography showed left ventricular akinesis and, since no improvement was noted on the following day, immunoglobulin (70 g/day for 2 days) was added to the therapy. The left ventricular ejection fraction increased to 25% and 40% at 12 and 36 h, respectively, representing a marked improvement in wall motion within a very short period. An endomyocardial biopsy specimen revealed focal lymphomononuclear infiltrate with adjacent myocytolysis, and acute lymphocytic myocarditis was diagnosed. Two days after administration of immunoglobulin, the serum level of interleukin-6 decreased rapidly from 180 to 5.9 pg/ml. In this patient, cardiac function improved immediately after immunoglobulin administration, suggesting the usefulness of this therapy. Three years after the diagnosis the patient is in good health, with steady normal left ventricular ejection fraction. We conclude that there are cases of acute myocarditis in which high-dose intravenous immunoglobulin therapy is effective.

Significance of transient left ventricular wall thickening in acute lymphocytic myocarditis

Transient left ventricular (LV) wall thickening is observed in patients with acute lymphocytic myocarditis. The present study was undertaken to clarify the significance of transient LV wall thickening in patients with this disease. The subjects comprised 25 patients with acute lymphocytic myocarditis. Echocardiography was used to measure the thickness of the interventricular septum (IVS) and the LV posterior wall (PW) at four time points after myocarditis onset – namely, on days 1–3, 6–8, 13–15, and 28–30 – to clarify the timing and frequency of wall thickening. The 25 patients were divided into a fulminant myocarditis group (n = 14) and a nonfulminant myocarditis group (n = 11), and the relationship between LV wall thickening and myocarditis severity was investigated. Left ventricular wall thickening was greatest on days 1–3 after myocarditis onset (IVS: 13.3 ± 3.2 mm; PW: 12.1 ± 2.6 mm), with this finding being noted in 14 of the 25 cases (56%). By days 6–8, the thickness of IVS had virtually normalized to 10.6 ± 1.6 mm (P < 0.0001) and that of PW to 10.2 ± 1.4 mm (P = 0.0006). The thickness of the IVS and PW on days 1–3 after myocarditis onset were 14.6 ± 3.7 and 13.0 ± 2.9 mm, respectively, in the fulminant group (P = 0.014), and 11.5 ± 0.9 and 10.9 ± 1.4 mm, respectively, in the nonfulminant group (P = 0.039). In lymphocytic myocarditis, LV wall thickening is greatest on days 1–3 after myocarditis onset and improves to near normal by days 6–8. Such transient LV wall thickening occurs in approximately 50% of cases. Left ventricular wall thickening was more marked in the fulminant compared with the nonfulminant group.

QRS-based assessment of myocardial damage and adverse events associated with cardiac sarcoidosis

BACKGROUND Cardiac sarcoidosis (CS) generates myocardial scar and arrhythmogenic substrate. CS diagnosis according to the Japanese Ministry of Health and Welfare guidelines relies, among others, on cardiac magnetic resonance imaging with late gadolinium enhancement (CMR-LGE). However, access to CMR-LGE is limited. The electrocardiography-based Selvester QRS score has been validated for identifying myocardial scar in ischemic/nonischemic cardiomyopathy, but its efficacy has not been tested to evaluate CS. OBJECTIVE The purpose of this study was to examine whether the QRS score can be applied to CS. METHODS CS-associated myocardial scar was assessed by both CMR-LGE and QRS scoring in patients with extra-CS (n = 59). RESULTS Of 59 patients, 35 (59%) were diagnosed with CS according to the Japanese Ministry of Health and Welfare guidelines. QRS-estimated scar mass positively correlated with that quantified by CMR-LGE (signal intensity ≥2SD above the reference; r = 0.68; P < .001). Receiver operating characteristic curves demonstrated optimal cutoffs of 9% CMR-LGE scar and 3-point QRS score to identify patients with CS. The areas under the curves of CMR-LGE and the QRS score were not significantly different (0.83 and 0.78, respectively; P = .27); both methods demonstrated similar diagnostic performance. A QRS score of ≥3 led to a higher incidence of CS-associated adverse events (death/fatal arrhythmia/heart failure hospitalization) than did a QRS score of <3 (35 ± 21 months of follow-up; P = .01). QRS score was an independent predictor of risk in multivariate analysis (P = .03). CONCLUSION The Selvester QRS scoring estimates CS-associated myocardial damage and identifies patients with CS equally well as CMR-LGE. A higher QRS score is also associated with an increased risk of life-threatening events in CS, indicating its potential use as a risk predictor.