Myocardial Fibrosis In Patients Research Articles

A Contemporary Approach to Hypertrophic Cardiomyopathy

A previously healthy 32-year-old female undergoes evaluation after a syncopal episode. Physical examination reveals a systolic ejection murmur. Echocardiography demonstrates a vigorous LV with marked asymmetric septal hypertrophy, systolic anterior motion of the mitral valve, and a 50–mm Hg outflow tract gradient. Family history is notable for unexpected death in 4 paternal family members. She has 2 children (Figure 1A). Figure 1. A, HCM is a genetic cardiovascular disease. This family shows autosomal dominant inheritance with &50% of the family affected and equal numbers of affected male (▪) and female (•) family members. The case patient is indicated by an arrow. Deceased individuals are indicated by a diagonal slash (all died suddenly). B, DNA sequence analysis can identify sarcomere mutations that cause HCM. Top, The normal sequence of a portion of the cardiac troponin T gene is displayed with a triplet codon, TCC, encoding serine present. Bottom, DNA sequence obtained from a patient with HCM. The normal sequence is present on the allele inherited from the unaffected parent; the other allele shows a single base-pair substitution of a thymidine residue for the normal cytosine residue. This triplet codon, TTC, encodes phenylalanine and results in the substitution of a phenylalanine residue for the normal serine residue at amino acid position 179. The prevalence of unexplained left ventricular hypertrophy (LVH) in the general population is estimated to be 1 in 500.1,2 Hypertrophic cardiomyopathy (HCM) caused by sarcomere mutations may account for up to 60% of unexplained LVH, making HCM the most common genetic cardiovascular disorder.3–5 Accurate diagnosis of HCM is important for appropriate management of major HCM comorbidities, including atrial fibrillation, stroke, heart failure, and sudden cardiac death (SCD).6,7 HCM typically is diagnosed by unexplained LVH on echocardiography. Age of onset of LVH ranges from early childhood to …

Relation Between Flow Reserve Capacity of Penetrating Intramyocardial Coronary Arteries and Myocardial Fibrosis in Hypertension: Study Using Transthoracic Doppler Echocardiography

The purpose of this study was to compare coronary flow reserve (CFR) capacity of penetrating intramyocardial coronary artery (PICA) using transthoracic Doppler echocardiography and biochemical marker of myocardial fibrosis in hypertension (HTN). In 58 patients (male:female ratio = 31:27; mean age 47 +/- 9 years) with chest pain and normal coronary angiogram findings, the width of color Doppler signal and peak diastolic velocity of PICA flow were measured in the myocardium just beneath the apical impulse window using transthoracic Doppler echocardiography. PICA-CFR and PICA-width ratio were calculated as the ratio of hyperemic to baseline peak diastolic velocity and as the ratio of hyperemic to baseline width after the adenosine infusion (140 mug/kg/min), respectively. Serum carboxy-terminal propeptide of procollagen type I, as a biochemical marker, was measured and patients were divided into 3 groups: 19 with HTN and PICA-CFR less than 2.0 (group A); 23 with HTN and PICA-CFR of 2.0 or more (group B); and 16 who were normotensive with PICA-CFR of 2.0 or more (group C). Baseline peak diastolic velocity for group A was higher than the other two groups (P < .005 vs groups B and C). PICA-width ratio was higher than the other two groups (P < .005 vs groups B and C). Serum propeptide of type I was 137.1 +/- 16.6 ng/mL in group A, 96.2 +/- 13.7 ng/mL in group B, and 78.8 +/- 11.2 ng/mL in group C (P < .0001 vs group B and group C). PICA-CFR was closely related to serum propeptide of type I (P < .001, r = -0.723). The impaired PICA-CFR is related to myocardial fibrosis in patients with HTN, chest pain, and normal coronary angiogram results.

New directions in the assessment and treatment of hypertensive heart disease

This article will review briefly the emerging new concepts in the diagnosis and treatment of myocardial fibrosis in patients with hypertensive heart disease. Although hypertensive heart disease is characterized clinically by development of left-ventricular hypertrophy in the absence of a cause other than arterial hypertension, changes in the composition of myocardial tissue also develop in arterial hypertension leading to structural remodeling of the myocardium (e.g. fibrosis). Recent available data on the determination of serum concentrations of collagen-derived serum peptides and quantitative analysis of echoreflectivity to address the presence of fibrosis in the myocardium of hypertensive patients are promising. In addition, preliminary data suggest that the goal of reducing myocardial fibrosis is achievable in patients with hypertensive heart disease using specific antihypertensive agents (e.g. those interfering with angiotensin II). The time has come to revisit the current management of hypertensive heart disease simply focused on detecting left-ventricular hypertrophy and controlling blood pressure to reduce left-ventricular mass. It is necessary to develop new approaches aimed at assessing and repairing alterations of myocardial structure and protect myocardial function and, in so doing, to reduce in a more-effective manner adverse risk associated with hypertensive heart disease.

Impact of the Angiotensin II Receptor Antagonist, Losartan, on Myocardial Fibrosis in Patients with End-Stage Renal Disease: Assessment by Ultrasonic Integrated Backscatter and Biochemical Markers

Myocardial fibrosis commonly occurs in patients with end-stage renal disease (ESRD) and has proven to be an important predictor for cardiovascular events. In experimental settings, angiotensin II type 1 receptor (AT1-R) antagonists have been shown to have anti-fibrotic effects on the myocardium independent of their antihypertensive effects. In this study, to investigate whether the AT1-R antagonist losartan would have such anti-fibrotic effects in patients, we administered losartan or, for purpose of comparison, the angiotensin-converting enzyme enalapril or Ca2+-antagonist amlodipine to patients with ESRD. Thirty-nine ESRD patients with hypertension were randomly assigned to receive losartan (n=13), enalapril (n=13), or amlodipine (n=13). Ultrasonic integrated backscatter (IBS) and serological markers of collagen type I synthesis and degradation were used to assess the degree of myocardial fibrosis just before and after 6 months of treatment. There were no significant differences in antihypertensive effects among the three agents. In the enalapril- and amlodipine-treated groups, the mean calibrated IBS values increased significantly after 6 months of treatment (enalapril: -31.6 +/- 1.3 to -29.4 +/- 1.2 dB, p=0.011; amlodipine: -30.6 +/- 1.4 to -27.2 +/- 1.2 dB, p=0.012). However, the mean calibrated IBS values in the losartan-treated group did not increase after 6 months of treatment (-31.2 +/- 1.7 to -31.3 +/- 1.4 dB, p=0.88). The ratio of the serum concentration of procollagen type I carboxy-terminal peptide to the serum concentration of collagen type I pyridinoline cross-linked carboxy-terminal telopeptide was significantly reduced in the losartan-treated group (42.6 +/- 4.6 to 34.4 +/- 3.6, p=0.038). The present study indicates that losartan more effectively suppresses myocardial fibrosis in patients with ESRD than does enalapril or amlodipine despite a comparable antihypertensive effect among the three drugs.

Valsartan Decreases Type I Collagen Synthesis in Patients With Hypertrophic Cardiomyopathy

Fibrosis, as well as myocyte hypertrophy, is the major determinant of prognosis in hypertrophic cardiomyopathy (HCM). Valsartan, an angiotensin II type 1 receptor blocker, may improve myocardial fibrosis in patients with HCM. Twenty-three patients with HCM were randomly divided into 2 groups: 11 patients had valsartan added to conventional treatment (V group) and 12 patients received the conventional therapy (C group). Plasma concentrations of brain natriuretic peptide (BNP), troponin T (TnT), aldosterone (ALDO), procollagen type I (PIP) and procollagen type III aminoterminal peptide (PIIINP) were measured before and 12 months after this study. Left ventricular wall thickness (LVWT) and ejection fraction (LVEF) were measured by echocardiography. PIP was decreased in the V group (123.2+/-63.1 ng/ml to 102.8+/-37.6, p<0.05), but unchanged in C group (110+/-40.5 ng/ml to 119.9+/-47.4, p=0.22). ALDO concentration was unchanged in the V group (88.5+/-26.2 pg/ml to 91.2+/-26.8, p=0.27), and increased in C group (92.6+/-36.6 ng/ml to 116.0+/-33.3, p<0.05). BNP, PIIINP, and TnT were unchanged by the treatment. There was no significant difference between the 2 groups in either LVWT or LVEF. Valsartan suppresses the synthesis of type I collagen in patients with HCM and this was associated with suppression of the increase in ALDO.

Repetitive worsening of chronic heart failure promotes myocardial fibrosis through enhanced oxidant stress in vivo

Background: Progression of myocardial fibrosis (MF) is vital for prognosis of patients with chronic heart failure (CHF). Oxidant stress (OS) has been suggested to regulate collagen metabolism at the level of cellular experiments. In this study we clarified a possible link between enhancement of OS in vivo and progression of MF in patients with CHF. Methods: Nineteen patients with CHF were enrolled at admission because of its acute worsening. After conventional treatment (20 ± 12days later), serum level of brain-type natriuretic peptide was decreased from 965.5 ± 704.8 (acute phase) to 311.5 ± 271.4pg/ml (chronic phase). At these two phases, we monitored: 1) urinary excretion of immunoreactive 8-iso-prostaglandin F 2α(8-isoPGF 2α), a marker for OS in vivo; 2) serum total anti-oxidant status (TAS); and 3) serum levels of procollagen type I carboxyterminal peptide (PIP) and carboxyterminal collagen type I telopeptide (CITP), biochemical markers for collagen synthesis and degradation, respectively. Results: We found that 8-isoPGF 2αand PIP levels were enhanced at acute versus chronic phase (353.9 ± 329.8 vs. 221.2 ± 131.2pg/mg creatinine, P = 0.01; 150.7 ± 55.8 vs. 99.7 ± 39.1ng/ml, P = 0.001; respectively). TAS did not change throughout the observation (0.95 ± 0.15 vs. 0.96 ± 0.16mM). CITP was increased from acute to chronic phase (7.4 ± 4.1 to 13.0 ± 8.2ng/ml, P = 0.0001). Conclusions: OS and collagen synthesis were enhanced at the acute worsening of CHF, suggesting that repetitive worsening of CHF promotes MF through OS.

Myocardial fibrosis evaluated by delayed-enhancement magnetic resonance imaging is associated with ventricular tachycardia in patients with cardiomyopathy

Background: Ventricular tachycardia (VT) is one of the important causes of morbidity and mortality in patients with cardiomyopathy. Recent clinical and experimental studies have demonstrated that myocardial fibrosis is associated with VT. Direct imaging of myocardial fibrosis is now possible with the use of gadolinium-chelate (Gd) enhanced T1-weighted magnetic resonance imaging named delayed-enhancement (DE) MRI. Purpose: The purpose of this study is to investigate the association between VT and myocardial fibrosis in patients with cardiomyopathy. Method: Twenty-one patients with cardiomyopathy (sixteen idiopathic dilated cardiomyopathy and five hypertrophic cardiomyopathy, 13 male, mean age 62.5 years) who had admitted to our hospital were investigated in this study. Patients were evaluated arrhythmia including VT by continuous ECG monitoring at least 5 days. VT was defined as continuous ventricular beats (more than 3 beats) with cycle length less than 500 ms. MRI was performed 15 minutes later after Gd injection, and high grade hyperenhancement was defined positive DE. Result: VT was seen in 8 patients (including 2 sustained VT). Positive DE was identified in 8 patients. There were no differences in clinical characteristics between positive and negative DE patients. Among negative DE (N = 13), VT was seen in 2 (15%), whereas among positive DE (N = 8), seen in 6 (75%) (P = 0.02). Conclusion: Myocardial fibrosis with positive DE is highly associated with VT in patients with cardiomyopathy.

Delayed-enhanced magnetic resonance imaging detects myocardial fibrosis in patients with chronic aortic valve disease

Delayed-enhanced magnetic resonance imaging detects myocardial fibrosis in patients with chronic aortic valve disease

Is the tissue harmonic imaging useful for estimation of the myocardial fibrosis in patients with cardiomyopathy?

Is the tissue harmonic imaging useful for estimation of the myocardial fibrosis in patients with cardiomyopathy?

The myocardial fibrosis in patients with dilated cardiomyopathy. The application of image analysis in the myocardial biopsies.

The aim of our study is to investigate whether myocardial fibrosis measured by image analysis may be considered as an important and accurate index of dilated cardiomyopathy and its prognosis. The study group consisted of 24 patients with dilated cardiomyopathy, which was diagnosed by echocardiography, radionuclide ventriculography, cardiac catheterization, and left ventricular endomyocardial biopsy. The patients' overall disability was conventionally expressed with the criteria for functional capacity. Using image analysis, the percentage of fibrosis in a total of 35 myocardial biopsies was accurately measured, followed by a study comparing the percentage of myocardial fibrosis and the clinical parameters (left ventricular ejection fraction and overall functional capacity), showing the degree of each patient's heart failure. A correlation was found among fibrosis, left ventricular ejection fraction, and overall functional capacity. The cases with small values of fibrosis (< 10%) have big values of ejection fraction and belong to Class I of overall functional capacity. The cases with big values of fibrosis (> 10%) belong to Classes III and IV of overall functional capacity and have small values of ejection fraction. The results of the comparative study were graphically presented and considered significant. Myocardial fibrosis measured by image analysis might be considered an important prognostic index of dilated cardiomyopathy.

Metabolic Complexities in Cardiac Imaging

For patients with advanced ischemic heart disease, positron emission tomography (PET) is a reimbursable method for identifying those suitable for revascularization. This will probably increase the use of PET in deciding whether potentially life-enhancing, but costly, interventions will be performed. In this issue of Circulation , an important article by Taegtmeyer and colleagues1 shows that it may not be possible to use the seductive, computer-derived colored images produced by PET as a quantitative measure of myocardial metabolic rate. These researchers have shown that accumulation of [2-18F]fluoro-2-deoxy-d-glucose (FDG), a widely used PET tracer, does not give an accurate measure of glucose metabolism under many of the physiological, metabolic, and hormonal conditions experienced by the heart. Modeling of FDG as a glucose analogue for glycolysis in the heart comes in large part from work in brain metabolism,2 where glucose is the major metabolic fuel and glycogen synthesis from glucose is essentially nil. In contrast, the heart is omnivorous in its choice of metabolic fuels, with a preference for fatty acids and with considerable glycogen synthesis and degradation.3 4 Consequently, expressions such as “myocardial glucose metabolism” and “myocardial glucose utilization” were coined in part out of recognition that FDG flux rates are unable to distinguish glycogen synthesis from glycolysis. In the heart, therefore, a measure of the rate of FDG accumulation may be just that—a measure of FDG accumulation and not a measure of metabolic rate. If one is to interpret the meaning of a change in FDG accumulation over time, a number of assumptions governing the rates of the reactions of glucose transport and phosphorylation must be met. The major reactions determining the extent of the intracellular use of glucose and FDG are transport into the cell, phosphorylation in the hexokinase reaction, dephosphorylation of glucose-6-phosphate …

New approach to the estimation of the extent of myocardial fibrosis in patients with dilated cardiomyopathy: Use of signal-averaged electrocardiography

To determine whether the extent of myocardial fibrosis in dilated cardiomyopathy could be estimated noninvasively, signal-averaged electrocardiograms were recorded in 32 patients with dilated cardiomyopathy, followed by left ventricular endomyocardial biopsy. The root mean square voltage for the last 40 msec (V40), the duration of the filted QRS complex (fQRSd) and the duration of low amplitude signals <40 μV (LAS) were obtained by signal-averaged electrocardiography. The extent of fibrosis in all biopsy samples was measured by the point-counting method. The extent of myocardial fibrosis closely correlated with fQRSd ( r = 0.623, p < 0.001), LAS ( r = 0.570, p < 0.001), and V40 ( r = −0.355, p < 0.05). When fibrosis was classified into intercellular and interfascicular types, the extent of intercellular fibrosis more closely correlated with fQRSd ( r = 0.695, p < 0.0001), LAS ( r = 0.640, p < 0.0001), and V40 ( r = −0.533, p < 0.005). These results suggest that signal-averaged electrocardiograms might be useful for estimation of the extent of myocardial fibrosis, especially intercellular fibrosis in patients with dilated cardiomyopathy.

Estimation of severity of myocardial fibrosis in patients with dilated cardiomyopathy by signal-averaged electrocardiograms

Estimation of severity of myocardial fibrosis in patients with dilated cardiomyopathy by signal-averaged electrocardiograms

Interstitial cell infiltrate and myocardial fibrosis in dilated cardiomyopathy: A special type of cardiomegaly corresponding to sequelae of myocarditis

We examined the relationship between interstitial cell infiltration and myocardial fibrosis in patients with clinically diagnosed dilated cardiomyopathy (DCM). Forty-two cases of DCM were divided into two groups, according to the mean number of the interstitial round cells per 10.2 x 10(4) square microns (Nic): the inflammatory group (Nic greater than or equal to 5) and noninflammatory group (Nic less than 5). The 12 cases in the inflammatory group were clinically similar to the 30 cases in the non-inflammatory group, but the inflammatory group exhibited a significantly (P less than 0.001) larger area of myocardial fibrosis (34.8% +/- 12.8% vs 17.5% +/- 8.2%), a significantly (P less than 0.01) higher frequency of diffuse perimyocytic-type fibrosis (83% vs 23%), fewer myocardial cells in the left ventricular wall (170 +/- 70 fibers vs 216 +/- 81 fibers), and significantly (P less than 0.01) greater hypertrophy of the myocytes (18.3 +/- 3.4 vs 15.3 +/- 2.7 microns). In addition, cases exhibiting marked fibrosis (fibrosis area greater than or equal to 25% of the myocardium) had a significantly higher Nic score (8.3 +/- 6.8) compared to cases with the less fibrotic type of DCM (4.0 +/- 5.7). We speculate that persistent or preceding inflammatory cell infiltration induces the myocardial fibrosis, especially the diffuse perimyocytic type, in the fibrosis-predominant type of DCM. Therefore, most of these cases may be a sequela of myocarditis, and more correctly termed post-myocarditic cardiomegaly.