mitochondrial cardiomyopathy can manifest with various cardiac phenotypes , such as left ventricle ( lv ) hypertrophy , dilatation , wall motion abnormality , and lethal ventricular arrhythmia ; these symptoms range from subclinical to critical conditions ( 1 ) .
the severity of myocardial dysfunction also predicts the prognosis of patients with mitochondrial disease , which highlights the importance of noninvasive assessment for myocardial dysfunction .
myocardial perfusion / metabolism mismatch ( the decreased uptake of technetium-99 m methoxyisobutylisonitrile [ tc - mibi]/the increased uptake of 123-labeled 15 - 4-iodophenyl-3-(r , s)-methyl - pentadecanoic acid [ i - bmipp ] ) has been reported in patients with mitochondrial cardiomyopathy ( 2,3 ) .
however , the previous studies did not compare the morphological images of patients with this condition . in the present case ,
we compared images of myocardial perfusion ( tc - mibi scintigraphy ) , fatty acid metabolism ( i - bmipp scintigraphy ) , and morphology ( cardiac magnetic resonance [ cmr ] and histology ) , and found that the images of our patient , who had a mismatch between perfusion and metabolism , were unique from those in the previous reports .
a 42-year - old man ( 157 cm , 48.4 kg ) was referred to our hospital with left chest pain , diabetes mellitus , and sensorineural hearing loss .
his mother had diabetes mellitus ; however , she did not have hearing loss or cardiovascular disease . at admission ,
his blood pressure was 121/79 mmhg , his heart rate was 82 beats / min with a regular pulse , and his percutaneous oxygen saturation was 98% in room air . although systolic heart murmurs were audible at the base ( 4lsb ) , there was no jugular venous distention , and his breathing sounds were normal .
hepatomegaly and splenomegaly were not present , and there was no edema in his extremities .
chest radiography revealed an increase in the cardiothoracic ratio ( 59% ) and mild pulmonary congestion ( fig .
twelve - lead electrocardiography detected a normal sinus rhythm and a high amplitude r wave with an inverted t wave in the left lateral precordial leads ( fig .
transthoracic echocardiography detected thickening of the lv walls ( septum , 16 mm ; posterior wall , 16 mm ) , as well as thickening of the right ventricle ( rv ) free wall , the slight dilatation of the lv ( lv end - diastolic diameter , 54 mm ) and diffuse lv systolic dysfunction ( ejection fraction , 40% ; using simpson 's method ) ( fig .
( a ) chest radiography reveals cardiomegaly ( cardiothoracic ratio , 59% ) and mild pulmonary congestion .
( b ) an electrocardiogram reveals a prominent r wave progression in v3 - 6 and a negative t wave in v5 - 6 .
( c , d ) transthoracic echocardiograms reveal the thickening of the left and right ventricle walls .
his levels of troponin t and n - terminal pro - brain natriuretic peptide were elevated to 0.107 ng / ml and 1,616 pg / ml , respectively .
his fasting glucose level was 172 mg / dl and his glycated hemoglobin was 7.0% .
the resting serum and cerebrospinal fluid lactate concentrations had increased to 27.0 mg / dl ( normal range , 3 - 17 mg / dl ) and 31.8 mg / dl ( normal range , 14 - 21 mg / dl ) , respectively .
brain computed tomography and magnetic resonance imaging revealed prominent calcification in the bilateral basal ganglia and cerebellar atrophy .
mitochondrial cdna sequencing detected a c.a3243 g mutation , and the patient was diagnosed with mitochondrial disease . to investigate the cause of his cardiac dysfunction , cardiac catheterization was performed after medical treatment .
his pulmonary artery pressure was normal ( 31/11 mmhg , mean 18 mmhg ) with an increase in the lv end - diastolic pressure ( 20 mmhg ) .
his cardiac index was preserved ( 3.08 l / min / m ) , and the coronary angiography findings were normal .
the microscopic findings revealed the rupture and degeneration of the myocardial fibers , which were surrounded by fibrosis(fig .
electron microscopy detected an increase in the number of mitochondria , which varied in size and morphology ( fig .
( a ) a light microscopy image reveals interstitial fibrosis and hypertrophic myocytes with vacuoles ( elastica - masson staining , 100 ) .
( b ) an electron microscopy image reveals an increased number of mitochondria with variable sizes and shapes .
the patient subsequently underwent resting tc - mibi cardiac scintigraphy ( 600 mbq ) , and single - photon emission computed tomography ( spect ) images were obtained at 60 minutes ( the early phase ) and 240 minutes ( the delayed phase ) after the injection ( 4 ) . in the early phase , the uptake of tc - mibi did not decrease ( fig .
the heart - to - mediastinum ratio was 2.89 in the early phase and 2.79 in the delayed phase , respectively .
the global washout rate in the delayed phase increased by 25% ( normal range : 11  5% ) .
the uptake of tc - mibi in the rv free wall appeared to be enhanced in the early phase ( fig .
3a).i - bmipp ( 111 mbq ) was administered intravenously , and spect images were obtained at 35 minutes after the injection ( 5 ) .
the uptake of i - bmipp was decreased in the anterior , septal , and inferior walls ( fig .
cmr was performed to estimate late gadolinium enhancement ( lge ) , which was observed from the midmyocardium to the epicardium of the anterior wall , as well as in the midmyocardium of the septal and inferior walls ( fig .
the tc - mibi / i - bmipp mismatch pattern ( non - decreased tc - mibi uptake / decreased i - bmipp uptake ) was confirmed via bull 's eye mapping ( fig .
( a ) the uptake of tc - mibi is not decreased in the early phase .
( b ) the uptake of i - bmipp is decreased in the anterior , septal , and inferior walls .
( c ) late gadolinium enhancement ( lge ) is observed from the midmyocardium to the epicardium of the anterior wall , as well as in the midmyocardium of the septal and inferior walls .
( d ) bull s eye mapping shows the tc - mibi / i - bmipp mismatch pattern ( non - decreased tc - mibi uptake / decreased i - bmipp uptake ) .
i - bmipp : 123-labeled 15 - 4-iodophenyl-3-(r , s)-methyl - pentadecanoic acid . during the patient 's hospitalization
we prescribed enalapril ( 2.5 mg / day ) and carvedilol ( 1.25 mg / day ) to expect preventive effect for the progression of cardiomyopathy ( 6,7 ) .
this is the first report to describe the relationship between myocardial perfusion , metabolism , and morphology , and to reveal a unique tc - mibi / i - bmipp mismatch pattern in a patient with mitochondrial cardiomyopathy .
our imaging findings revealed a decrease in the uptake of i - bmipp , using lge in cmr as an anatomical reference .
in contrast , previous studies have reported an increase in the uptake of i - bmipp in mitochondrial cardiomyopathy ( without providing anatomical reference images ) .
the mechanism underlying this observation may be related mitochondrial respiratory chain failure , which leads to the excessive production of nicotinamide adenine dinucleotide ( nadh ) , which then causes an increase in the concentration of glycerol-3-phospate ( to oxidize the excess nadh ) and ultimately leads to increased levels of triglycerides . according to this mechanism , i - bmipp ( a fatty acid analogue )
is incorporated into the cardiomyocytes ' pool of triglycerides ( 3,8 ) . in our patient , the distribution of the areas that showed a low uptake of i - bmipp was consistent with the distribution of lge , which suggests that the low uptake of i - bmipp might be correlated with the low number of viable myocytes or fibrosis , rather than an energy production from fatty acid metabolism to the glycolytic pathway ( as in other cardiomyopathies ) .
thus , the extent of the i - bmipp uptake may depend on the balance between the mitochondrial respiratory chain failure and the viable myocyte mass , whereby the loss of a certain number of myocytes might outweigh the increased uptake of i - bmipp .
the uptake of tc - mibi in the early phase was not decreased in this case .
one of the interpretations of the preserved uptake of tc - mibi may be the presence of preserved blood flow and viable myocytes . in this case , the unique lge pattern ( obscure margins and inhomogeneous intensity ) may reflect the scattered viable myocytes that were surrounded by fibrosis , which were also detected in our histological examination .
this pattern is distinct from the homogeneous lge pattern that is observed in cases of myocardial infarction .
it is possible that the preserved myocytes in the lge - positive area affect the uptake of tc - mibi .
the volume effect of the thickening lv wall might also explain the non - decreased uptake of tc - mibi ( similar to the effect in patients with hypertrophic cardiomyopathy ) and the enhanced uptake of tc - mibi in the rv free wall .
furthermore , the washout rate for tc - mibi increased in this case , which is consistent with the findings of previous studies ( 2,3,8 ) . in this context ,
mitochondrial dysfunction impairs the retention of the tc - mibi tracer in myocytes , which leads to an increased washout rate for tc - mibi .
nevertheless , our unique tc - mibi / i - bmipp mismatch pattern ( non - decreased tc - mibi uptake / decreased i - bmipp uptake ) is distinct from the patterns in previous reports ( decreased tc - mibi uptake / increased i - bmipp uptake ) ( 2,3 ) .
the tc - mibi / i - bmipp mismatch pattern in the present case can be considered to be a nonspecific phenomenon in patients with dilated cardiomyopathy ( 9 ) .
this discrepancy may be related to the stages or diverse phenotypes of mitochondrial cardiomyopathy . in conclusion ,
multimodality imaging allows us to evaluate the relationship between myocardial perfusion , metabolism , and morphology .
further studies are needed to elucidate the complex processes of myocardial damage in patients with mitochondrial cardiomyopathy .
 a 42-year - old man was referred to our hospital due to chest pain , diabetes mellitus , and sensorineural hearing loss . 
 transthoracic echocardiography revealed diffuse left ventricular hypokinesis . 
 he was diagnosed with mitochondrial disease and a c.a3243 g mutation was identified in his mitochondrial dna . 
 this case of mitochondrial cardiomyopathy demonstrated a low uptake of 123i - bmipp , while the uptake of 99mtc - mibi was preserved . 
 in contrast , previous reports have noted the increased uptake of123i - bmipp and the decreased uptake of 99mtc - mibi . 
 this is the first study to show this unique 99mtc - mibi/123i - bmipp mismatch pattern . 
 we also discuss the relationships among the cardiac scintigraphy , cardiac magnetic resonance imaging , and histopathology findings . 
Introduction
Case Report
Discussion
The authors state that they have no Conflict of Interest (COI).