Reduced Perfusion Reserve Research Articles

Myocardial stress perfusion magnetic resonance in children with hypertrophic cardiomyopathy.

Microvascular dysfunction in hypertrophic cardiomyopathy has been associated with poor clinical outcome. Several studies have demonstrated a reduced perfusion reserve proportional to the magnitude of the hypertrophy. We investigated the utility of stress perfusion cardiac MRI to detect microvascular dysfunction in children with hypertrophic cardiomyopathy. From January 2016 to January 2017, 13 patients, with a mean age of 15.3 years, with hypertrophic cardiomyopathy underwent regadenoson stress perfusion cardiac MRI (1.5-T Siemens Aera). A single-shot, T1-weighted saturation recovery gradient echo was used for first-pass perfusion in a multiple-slices group, including three short-axis slices and one four-chamber slice. Coronary vasodilatory stress was achieved using bolus injection of regadenoson (lexiscan 0.4 mg/5 ml) and dynamic perfusion during rest and stress performed by administering 0.05 mmol/kg of gadolinium contrast agent (gadoteridol) injected at a rate of 3.5 ml/s, followed by assessment of viability using two-dimensional phase-sensitive inversion recovery of the entire myocardium. All patients completed protocols with no interruptions. In all, seven patients developed perfusion defects after the administration of regadenoson. Asymmetric septal hypertrophy was the most common pattern of hypertrophic cardiomyopathy (n=4) in those with abnormal perfusion. A total of four patients with perfusion defects had a maximum wall thickness <30 mm. The finding of perfusion defects in areas without late gadolinium enhancement in some of our patients indicates that gadolinium enhancement by itself could underestimate the true extension of microvascular disease. Out of seven patients, five patients with positive stress cardiac MRI have undergone implantable cardioverter defibrillator placement based on current guidelines. Regadenoson stress cardiac MRI is feasible and clinically valuable in paediatric patients. It is particularly effective in unmasking abnormal myocardial perfusion in the presence of microvascular dysfunction in children with hypertrophic cardiomyopathy.

Global fibroblast activation throughout the left ventricle but localized fibrosis after myocardial infarction

Fibroblast (Fb) differentiation and interstitial fibrosis contribute to cardiac remodeling and loss of function after myocardial infarction (MI). We investigated regional presence and regulation of fibrosis in a pig MI model. In vivo analysis of regional function and perfusion defined three regions: the scar, the myocardium adjacent to the scar (MIadjacent, reduced function, reduced perfusion reserve), and the remote myocardium (MIremote, minimal functional deficit, maintained perfusion). Interstitial and perivascular fibrosis, and increase of collagen type I, was only observed in the MIadjacent. Fb activated protein-alpha (FAP-α) was enriched in MIadjacent compared to MIremote. TGF-β1, which triggers Fb differentiation, was upregulated in both MIadjacent and MIremote, whereas lysyl oxidase, a regulator of collagen cross-linking, and the proteoglycans decorin and biglycan were only increased in the MIadjacent. Fb isolated and cultured for 4 days had myoFb characteristics with little difference between MIremote and MIadjacent, although RNA sequencing revealed differences in gene expression profiles. Fbs from all regions maintained proliferative capacity, and induced contraction of 3-D collagen matrices but scar myoFb was more effective. These data suggest that after MI, signaling through TGF-β1, possibly related to increased mechanical load, drives Fb activation throughout the left ventricle while regional signaling determines further maturation and extracellular matrix remodeling after MI.

Impairment of Subendocardial Perfusion Reserve and Oxidative Metabolism in Nonischemic Dilated Cardiomyopathy

BackgroundCardiac magnetic resonance (CMR) and [11C]acetate positron emission tomography (PET) were used to assess the hypothesis that patients with nonischemic dilated cardiomyopathy (NIDCM) have decreased subendocardial perfusion reserve and impaired oxidative metabolism, consistent with the concept of “energy starvation” in heart failure (HF). Methods and ResultsCMR myocardial perfusion was evaluated in 13 NIDCM patients and 15 control subjects with coronary risk factors and normal myocardial perfusion. The NIDCM patients underwent [11C]acetate PET. The myocardial perfusion index (MPI) was calculated as the normalized rate of myocardial signal augmentation following gadolinium contrast injection. Hyperemic transmural, subendocardial, and subepicardial MPI were reduced in NIDCM compared with control subjects [0.13 vs 0.18 (P < .001), 0.13 vs 0.17 (P < .001), and 0.13 vs 0.17 (P = .008), respectively]. The subendocardial perfusion reserve was 1.59 ± 0.21 vs 1.86 ± 0.32 for the subepicardium (P = .002), demonstrating reduced perfusion reserve. The myocardial oxidative metabolic rate (kmono) per unit demand (rate-pressure product) was reduced in proportion to perfusion reserve (P = .02) ConclusionsImpaired subendocardial perfusion reserve in NIDCM confirmed results previously attained only in animal models. Impaired perfusion and impaired oxidative metabolism are consistent with subendocardial energy starvation in HF.

Role of Noninvasive Imaging in the Diagnosis of Cardiac Allograft Vasculopathy

Cardiac allograft vasculopathy (CAV) is common, with a prevalence of 52% at 10 years after transplantation, and represents a leading cause of death beyond the first year, responsible for approximately 15% of deaths annually.1 It is characterized by diffuse and concentric intimal proliferation, typically involving the intramural as well as epicardial coronary arteries. Its diagnosis is difficult to establish clinically because of denervation of the transplanted heart. Consequently, it presents late with silent myocardial infarction, progressive heart failure, or arrhythmic sudden death.2 Screening is therefore required for its early detection. Although coronary intravascular ultrasound (IVUS) is considered the gold-standard technique for detecting the anatomic features of CAV (Table 1), its broad clinical use in this context is limited by cost and lack of widespread expertise, and its evaluation is limited to epicardial vessels.3 Coronary angiography, performed annually or biannually, remains the most common clinical screening method.4 However, because of the diffuse nature of CAV with a lack of normal reference segments and the relatively late occurring luminal narrowing, the sensitivity of angiography is as low as 30% when compared with IVUS (Figure 1).5 As a result, complications frequently occur before disease is evident angiographically.6 Furthermore, angiography is associated with significant albeit uncommon complications (overall complication rate, 7.4/1000 procedures, including rates of 0.65/1000, 1.6/1000, and 0.72/1000 for cerebrovascular accidents, vascular complications, and death, respectively), is disliked by transplant recipients, is costly, and repeated studies are associated with an important cumulative radiation dose.7 View this table: Table 1. Stanford Classification of CAV Severity on IVUS Figure 1. Invasive assessment of cardiac allograft vasculopathy (CAV) in a patient with severe disease, highlighting the limited sensitivity of conventional coronary angiography. Although no left anterior descending (LAD) flow-limiting stenoses are seen on angiography ( A ), intravascular ultrasound ( B ) shows significant intimal thickening, measuring up to …

Reduction of N‐acetyl Aspartate in Bilateral Cerebral Tissue in Relation to Compromised Cerebrovascular Reserve Capacity as Investigated by Proton MR Spectroscopy and Acetazolamide Test

AbstractPatients with a symptomatic occlusion of the internal carotid artery or middle cerebral artery are at risk of future stroke. The magnetic resonance spectroscopy (MRS) study in such patients has shown no evidence of the reduced N‐acetyl aspartate (NAA) in regions ipsilateral to a carotid stenosis or occlusion. This result may be partially attributed to the location of MRS voxel in areas without the reduced perfusion reserve. We hypothesize that it is possible to observe the abnormal metabolism if MRS voxel can be placed in areas with the reduced cerebrovascular reserve. Perfusion measurements may allow the assessment of cerebral perfusion reserve by challenge such patients with cerebral vasodilation drugs such as acetazolamide. 38 patients with chronic occlusion or severe stenosis of the internal carotid artery or middle cerebral artery with or without infarction have been performed with challenge test and MRS studies. In addition, 12 normal volunteers were performed with MRS but without challenge test. Perfusion reserve was evaluated by ΔrCBF% and post‐challenge mean transient time (MTT). A correlation was observed between ΔrCBF% and post‐challenge MTT (r = −0.67). Patients without acute infarction were divided into two groups as mild and severe, compromised in according to the post‐challenge hemodynamic data. The spectra for analysis were recorded from voxels in bilateral temporo‐parietal white matter area without MRI visible infarction. Metabolite concentration was normalized to the concentration of creatine (Cr). Between normal and severe group, the NAA/Cr ratios in bilateral cerebral tissue were shown to be significantly differences, so do those between mild and severe group (p &lt; 0.01). In this work, we demonstrated that abnormal metabolism can be detected by MRS method. NAA/Cr ratio may also be reduced in the unaffected contralateral brain. A threshold level of NAA/Cr was shown to be sustainable until the irreversible ischemic ictus occurs.

Reduced Perfusion Reserve in Leukoaraiosis Demonstrated Using Acetazolamide Challenge 123I-IMP SPECT

We examined the relationship between the perfusion reserve as measured by acetazolamide (ACZ)-challenge N-isopropyl-I-123-p-iodoamphetamine (IMP)-single-photon emission computed tomography (SPECT) and the degree of leukoaraiosis (LA) as estimated using magnetic resonance imaging. In 51 patients receiving IMP-SPECT with the resting state and ACZ challenge, the unaffected cerebral hemispheres were included in the present study. Mean cerebral blood flow (CBF) in the resting state and ACZ reactivity were acquired. Absolute CBF value and ACZ reactivity were compared among patients with LA grades 0, 1, and 2. The relationship between mean age and LA grade was also assessed. No significant difference in the absolute CBF value in the resting state was observed among the 3 LA groups. Although vasoreactivity in LA grade 0 did not differ from that in grade 1, vasoreactivity in LA grade 2 was significantly lower (P < 0.05) than that in grades 0 or 1. The perfusion reserve is impaired in advanced LA.

Coronary Artery Calcification and Myocardial Perfusion in Asymptomatic Adults: The MESA (Multi-Ethnic Study of Atherosclerosis)

This study assessed the cross-sectional association between coronary artery calcification (CAC) and myocardial perfusion in an asymptomatic population. Clinical studies showed that the prevalence of stress-induced ischemia increased with CAC burden among patients with coronary heart disease (CHD). Whether an association between CAC and myocardial perfusion exists in subjects without a history of CHD remains largely unknown. A total of 222 men and women, ages 45 to 84 years old and free of CHD diagnosis, in the Minnesota field center of the MESA (Multi-Ethnic Study of Atherosclerosis) were studied. Myocardial blood flow (MBF) was measured using magnetic resonance imaging during rest and adenosine-induced hyperemia. Perfusion reserve was calculated as the ratio of hyperemic to resting MBF. Agatston CAC score was determined from chest multidetector computed tomography. Mean values of hyperemic MBF and perfusion reserve, but not resting MBF, were monotonically lower across increasing CAC levels. After adjusting for age and gender, odds ratios (95% confidence intervals) of reduced perfusion reserve (<2.5) for subjects with CAC scores of 0, 0.1 to 99.9, 100 to 399, and > or =400 were 1.00 (reference), 2.16 (0.96 to 4.84), 2.81 (1.04 to 7.58), and 4.99 (1.73 to 14.4), respectively. Further adjustment for other coronary risk factors did not substantially modify the association. However, the inverse association between perfusion reserve and CAC attenuated with advancing age (p for interaction < 0.05). Coronary vasodilatory response was associated inversely with the presence and severity of CAC in asymptomatic adults. Myocardial perfusion could be impaired by or manifest the progression to subclinical coronary atherosclerosis in the absence of clinical CHD.

Positron Emission Tomographic Evaluation of Regulation of Myocardial Perfusion in Physiological (Elite Athletes) and Pathological (Systemic Hypertension) Left Ventricular Hypertrophy

Myocardial perfusion (MP) may differ in physiologic and pathologic left ventricular hypertrophy (LVH). We compared MP in LVH in elite athletes and patients with hypertension with healthy, age-matched subjects. We included 12 rowers with LVH, 19 patients with hypertension with LVH, and 2 age-matched groups of healthy subjects (n = 11 and n = 12). The left ventricular mass index was determined echocardiographically. MP was measured by N-13 ammonia positron emission tomography. The maximal perfusion and perfusion reserve were studied using dipyridamole, and endothelial function was assessed by a cold pressor test. The degree of LVH was similar in athletes and those with hypertension. Compared with controls, athletes had 20% lower baseline MP (p <0.05), a similar response to the cold pressor test, and a higher perfusion reserve (31%, p <0.05). The patients with hypertension had a 25% higher baseline MP (p <0.05), a reduced increase during the cold pressor test (12% vs 25% in controls, p <0.05), and a reduced perfusion reserve (27% lower, p <0.001). The peak global perfusion (MP x left ventricular mass index) was 62% higher in athletes (p <0.05) than in controls, but the peak global perfusion in patients with hypertension did not differ from that of controls. In conclusion, physiologic LVH in athletes is suited for a high peak workload at the cost of only a small increase in basal myocardial oxygen consumption. In contrast, LVH in the presence of hypertension is a good adaptation to the increased baseline workload with maintained maximal cardiac performance. Endothelial dysfunction may contribute to the reduced perfusion reserve seen in hypertensive LVH.

Regional Heterogeneity of Myocardial Perfusion in Healthy Human Myocardium: Assessment with Magnetic Resonance Perfusion Imaging #

The knowledge of myocardial perfusion in healthy volunteers is fundamental for evaluation of patients with ischemic heart disease. The study was conducted to determine range, regional variability, and transmural gradient of myocardial perfusion in normal volunteers with Magnetic Resonance Perfusion Imaging (MRPI). Perfusion was assessed in 17 healthy volunteers (age: 20-47 yr, 11 males) at rest and adenosine-induced hyperemia using a 1.5 T MR scanner. Perfusion was quantified (mL/g/min) for the transmural myocardium and separately for the endo- and epimyocardium in the anterior, lateral, posterior, and septal left ventricular wall using the Fermi model for constrained deconvolution. Regional variabilities for resting, hyperemic perfusion, and perfusion reserve were 22 +/- 8%, 21 +/- 10%, and 35 +/- 18%. Mean resting, hyperemic perfusion, and perfusion reserve were 1.1 +/- 0.4 mL/g/min, 4.2 +/- 1.1 mL/g/min, and 4.1 +/- 1.4. Perfusion in the septum was higher at rest (1.3 +/- 0.3 mL/g/min vs. 1.0 +/- 0.3 mL/g/min, p < 0.05) and lower during hyperemia (3.6 +/- 0.8 mL/g/min vs. 4.5 +/- 1.1 mL/g/min, p < 0.03), resulting in a reduced perfusion reserve (PR) (3.2 +/- 0.9 vs. 4.5 +/- 1.4, p < 0.01) in the septum vs. the combined anterior, lateral, and posterior segments. Resting (0.9 +/- 0.3 mL/g/min vs. 1.4 +/- 0.5 mL/g/min, p < 0.01), but not hyperemic perfusion, was lower in the epi- vs. endomyocardium, resulting in a higher epimyocardial PR (4.8 +/- 1.8 vs. 3.5 +/- 1.4, p < 0.01) in all regions but the septum, where endo- and epimyocardial perfusion and perfusion reserve were not different. A considerable regional variability of myocardial perfusion was confirmed with MRPI. The exceptional anatomical position of the septum is reflected by the lack of a perfusion gradient, which was demonstrated in all other regions but the septum.

Rational approach to treatment of moyamoya disease in childhood.

Early diagnosis and treatment of moyamoya disease in children is essential to minimize residual mental and physiologic deficits. Current treatment of childhood moyamoya disease in Japan, preoperative evaluation of perfusion reserve as a surgical indication, and the role of noninvasive follow-up by magnetic resonance angiography are reported. Approximately 20% of children with definite moyamoya disease were observed or treated medically. Among surgical procedures, single indirect bypass surgery was used in approximately 30% of all patients; combinations of direct and indirect bypass surgery, 20%; and multiple-indirect bypass surgery, 18%. Both adequate understanding of the primary condition and determination of optimal treatment, including specific operative procedures, required evaluation of cerebral circulation and metabolism. Surgical indications included reduced perfusion reserve in affected brain by positron emission tomography or single photon emission tomography with administration of acetazolamide or a CO2 load. Postoperative improvements of cerebral perfusion reserve show better correlation with disappearance of ischemic attacks than does angiographically demonstrated collateral formation. Follow-up evaluation with magnetic resonance angiography has advantages over conventional angiography because it is noninvasive and avoids general anesthesia.

Cerebral revascularization by omental free flap using contralateral superficial temporal vessels as recipient vessels: Case report

Although the most common technique of cerebral revascularization is superficial temporal artery to middle cerebral artery bypass, we occasionally encounter a situation in which the ipsilateral superficial temporal artery is not available. Treatment may require several techniques including long vein graft bypass. A 54-year-old man experienced transient ischemic attacks, and cerebral angiography revealed occlusion of the right common carotid artery. Cerebral blood flow study revealed reduced perfusion reserve capacity of the right cerebral hemisphere. We applied an omental free flap to the brain surface using the contralateral superficial temporal vessels as recipient vessels. Cerebral blood flow study revealed improvement of perfusion reserve capacity. Cerebral angiography revealed good collateral circulation from the omentum to the brain. The patient has not experienced a transient ischemic attack, following additional ligation of the occipital artery 13 months after the first operation. Because an omental flap has a long pedicle and its circulation can be monitored easily, this method is safe and as effective as a long bypass graft in a patient such as ours in whom the ipsilateral superficial temporal artery is not available for anastomoses.

The value of quantitative myocardial perfusion imaging with Positron Emission Tomography in coronary artery disease

Positron Emission Tomography (PET) is the only available technique that permits quantification of regional myocardial perfusion in humans. To this end, tracer kinetic models and appropriate tracers such as 13N-Ammonia and 15O labeled water are required. Quantification is possible because accurate radioactivity quantities can be measured externally, both for the vascular and myocardial compartments. Normal value for baseline and maximal perfusion after pharmacologically induced vasodilatation of the resistance microcirculatory vessels are age-dependent. The functional hemodynamic significance of epicardial stenoses can be estimated from the progressive reduction in coronary perfusion reserve, which decreases progressively when stenosis severity reaches 40% in diameter. The effect of revascularization procedures such as CABG and PTCA can be objectively measured. In addition, there is increasing evidence from PET studies that resistive vessel dysfunction (probably through endothelial factors) contributes to the reduced perfusion reserve in patients with epicardial coronary artery disease. Therefore quantification of myocardial perfusion with PET appears an ideally suited endpoint for primary and secondary prevention trials.