Left ventricular longitudinal strain is a major determinant of CT-derived three-dimensional maximum principal strain: comparison with two-dimensional speckle tracking echocardiography.

Computed tomography (CT)-derived three-dimensional maximum principal strain (MP-strain) can provide incremental value to coronary CT angiography for cardiac dysfunction assessment with high diagnostic performance in patients with myocardial infarction. Global longitudinal strain (GLS) measured using two-dimensional speckle tracking echocardiography (2D-STE) is more sensitive than left ventricular ejection fraction (LVEF) for detecting early myocardial dysfunction. We aimed to compare CT-derived MP-strain with each of 2D-STE-derived strains (i.e., longitudinal, circumferential, and radial strains), and identify the major determinants of CT-derived MP-strain among 2D-STE-derived strains. We studied 51 patients who underwent cardiac CT and echocardiography. CT images were reconstructed at every 5% (0-95%) of the RR interval. A dedicated workstation was used to analyze CT-derived MP-strain on the 16-segment model. We calculated CT-derived global MP-strain with all the 16 segments on a per patient basis. Pearson's test was used to assess correlations between CT-derived MP-strain and STE-strain at global and segmental levels. The intra-class correlation coefficient for interobserver agreement for CT-derived global MP-strain was 0.98 (95% confidence interval 0.96-0.99). The low-CT-derived global MP-strain group (≤ 0.43) had more patients with LV dysfunction than the high-CT-derived global MP-strain group (> 0.43). CT-derived global MP-strain was associated with STE-GLS (r = 0.738, P < 0.001), global circumferential strain (r = 0.646, P < 0.001), and global radial strain (r = 0.432, P = 0.001). In multivariate analysis, STE-GLS had the strongest association to CT-derived global MP-strain among three directional STE-strains and LVEF by echocardiography (standardized coefficient = - 0.527, P < 0.001). STE-GLS is a major determinant of CT-derived global MP-strain. CT-derived MP-strain may enhance the value of coronary CT angiography by adding functional information to CT-derived LVEF.

Characteristics of the left ventricular three-dimensional maximum principal strain using cardiac computed tomography: reference values from subjects with normal cardiac function.

OBJECTIVES: This study evaluated the characteristics of left ventricular maximum principal strain (LV-MPS) using cardiac CT in subjects with normal LV function. METHODS: Of 973 subjects who underwent retrospective electrocardiogram-gated cardiac CT using a third-generation dual-source CT without beta-blocker administration, 31 subjects with preserved LV ejection fraction ≥ 55% assessed by echocardiography without coronary artery stenosis and cardiac pathology were retrospectively identified. CT images were reconstructed every 5% (0-95%) of the RR interval. LV-MPS and the time to peak (TTP) were analyzed using the 16-segment model and compared among three levels (base, mid, and apex) and among four regions (anterior, septum, inferior, and lateral) using the Steel-Dwass test. The intra- and inter-observer reproducibilities for LV-MPS were calculated using intraclass correlation coefficients (ICCs). RESULTS: The intra- and inter-observer ICCs (95% confidence interval) for peak LV-MPS were 0.96 (0.94-0.97) and 0.94 (0.92-0.96), respectively. The global peak LV-MPS (median, inter-quantile range) was 0.59 (0.55-0.72). The regional LV-MPS significantly increased in the order of the basal (0.54, 0.49-0.59), mid-LV (0.57, 0.53-0.65), and apex (0.68, 0.60-0.84) (p < 0.05, in each), and was significantly higher in the lateral wall (0.66, 0.60-0.77), while that in the septal region (0.47, 0.44-0.54) was the lowest among the four LV regions (all p < 0.05). No significant difference in TTP was seen among the myocardial levels and regions. CONCLUSION: CT-derived LV-MPS is reproducible and quantitatively represents synchronized myocardial contraction with heterogeneous values in subjects with normal LV function. KEY POINTS: • CT-derived left ventricular maximum principal strain analysis allows highly reproducible quantitative assessments of left ventricular myocardial contraction. • In subjects with normal cardiac function, the peak value of CT-derived left ventricular maximum principal strain is the highest in the apical level and in the lateral wall and the lowest in the septum. • The regional peak left ventricular maximum principal strain shows intra-ventricular heterogeneity on a per-patient basis, but myocardial contraction is globally synchronized in subjects with normal cardiac function seen on cardiac CT.

Per-Vessel Level Analysis of Fractional Flow Reserve and Instantaneous Wave-Free Ratio Discordance　- Insights From the AJIP Registry.

BACKGROUND: The per-vessel level impact of physiological pattern of disease on the discordance between fractional flow reserve (FFR) and instantaneous wave-free ratio (iFR) has not been clarified.Methods and Results:Using the AJIP registry, vessels with FFR/iFR discordance (133/671 [19.8%]) were analyzed. In the left anterior descending artery (LAD), physiologically diffuse disease, as assessed by pressure-wire pullback, was associated with FFR-/iFR+ (83.3% [40/48]), while physiologically focal disease was associated with FFR+/iFR- (57.4% [31/54]), significantly (P<0.0001). These differences were not significant in non-LAD (P=0.17). CONCLUSIONS: The impact of physiological pattern of disease on FFR/iFR discordance is more pronounced in the LAD.

On-Site Computed Tomography-Derived Fractional Flow Reserve Using a Machine-Learning Algorithm　- Clinical Effectiveness in a Retrospective Multicenter Cohort.

BACKGROUND: This study evaluated the diagnostic capability of on-site coronary computed tomography-derived computational fractional flow reserve (CT-FFR) determinations for detecting coronary artery disease (CAD), as assessed by invasive fractional flow reserve (FFR).Methods and Results:Seventy-four patients with coronary artery calcium scores <1,500 who underwent coronary CT angiography (CTA) and invasive FFR measurements within 90 days were retrospectively reviewed. CT-FFR was computed using a prototype machine-learning (ML) algorithm in 91 vessels; 47 vessels of 42 patients were determined to have significant CAD (FFR ≤0.8). Correlation between CT-FFR and FFR was good (r=0.786, P<0.001). Per-vessel area under the curve was significantly larger for CT-FFR (0.907, 95% confidence interval: 0.828-0.958) than for CTA stenosis ≥50% (0.595, 0.487-0.697) or ≥70% (0.603, 0.495-0.705) (both P<0.001). Standard coronary CTA classifications recommended further functional tests in 57 patients with moderate or worse stenosis on CTA. CT-FFR analysis (mean analysis time: 16.4±7.5 min) corrected the standard coronary CTA classification in 18 of 74 patients and confirmed it in 45 of 74 patients. Thus, the per-patient diagnostic accuracy of the classifications was improved from 66% (54-77%) to 85% (75-92%). CONCLUSIONS: On-site CT-FFR based on a ML algorithm can provide good diagnostic performance for detecting hemodynamically significant CAD, suggesting the high value of coronary CTA for selected patients in clinical practice.

Impact of Knowledge-Based Iterative Model Reconstruction on Image Quality and Hemodynamic Parameters in Dynamic Myocardial Computed Tomography Perfusion Using Low-Tube-Voltage Scan: A Feasibility Study.

OBJECTIVE: Knowledge-based iterative model reconstruction (IMR) yields diagnostically acceptable image quality in low-dose static computed tomography (CT). We aimed to evaluate the feasibility of IMR in dynamic myocardial computed tomography perfusion (CTP). METHODS: We enrolled 24 patients who underwent stress dynamic CTP using a 256-slice CT. Images were reconstructed using filtered back projection (FBP), hybrid IR, and IMR. Image quality and hemodynamic parameters were compared among three algorithms. RESULTS: Qualitative image quality and contrast-to-noise ratio were significantly higher by IMR than by FBP or hybrid IR (visual score: 4.1 vs. 3.0 and 3.5; contrast-to-noise ratio: 12.4 vs. 6.6 and 8.4; P < 0.05). No significant difference was observed among algorithms in CTP-derived myocardial blood flow (1.68 vs. 1.73 and 1.70 mL/g/min). CONCLUSIONS: The use of knowledge-based iterative model reconstruction improves image quality without altering hemodynamic parameters in low-dose dynamic CTP, compared with FBP or hybrid IR.

Late iodine enhancement computed tomography with image subtraction for assessment of myocardial infarction.

OBJECTIVE: To evaluate the feasibility of image subtraction in late iodine enhancement CT (LIE-CT) for assessment of myocardial infarction (MI). METHODS: A comprehensive cardiac CT protocol and late gadolinium enhancement MRI (LGE-MRI) was used to assess coronary artery disease in 27 patients. LIE-CT was performed after stress CT perfusion (CTP) and CT angiography. Subtraction LIE-CT was created by subtracting the mask volume of the left ventricle (LV) cavity from the original LIE-CT using CTP dataset. The %MI volume was quantified as the ratio of LIE to entire LV volume, and transmural extent (TME) of LIE was classified as 0%, 1-24%, 25-49%, 50-74% or 75-100%. These results were compared with LGE-MRI using the Spearman rank test, Bland-Altman method and chi-square test. RESULTS: One hundred twenty-five (29%) of 432 segments were positive on LGE-MRI. Correlation coefficients for original and subtraction LIE-CT to LGE-MRI were 0.79 and 0.85 for %MI volume. Concordances of the 5-point grading scale between original and subtraction LIE-CT with LGE-MRI were 75% and 84% for TME; concordance was significantly improved using the subtraction technique (p <0.05). CONCLUSION: Subtraction LIE-CT allowed more accurate assessment of MI extent than the original LIE-CT. KEY POINTS: • Subtraction LIE-CT allows for accurate assessment of the extent of myocardial infarction. • Subtraction LIE-CT shows a close correlation with LGE-MRI in %MI volume. • Subtraction LIE-CT has significantly higher concordance with TME assessment than original LIE-CT.

Intravascular Ultrasound-Derived Virtual Fractional Flow Reserve for the Assessment of Myocardial Ischemia.

BACKGROUND: Fractional flow reserve (FFR) is widely used for the assessment of myocardial ischemia. Intravascular ultrasound (IVUS) is an intracoronary imaging method that provides information about lumen and vessel morphology. Previous studies on the expanded use of IVUS to identify functional ischemia have noted an association between anatomy and physiology, but IVUS-derived minimum lumen area (MLA) has a weak-moderate correlation with myocardial ischemia compared with FFR. We developed a method to calculate FFR using IVUS-derived anatomical information for the assessment of myocardial ischemia. The aims of this study were to investigate the relationship between wire-based FFR and IVUS-derived FFR (IVUS-FFR) and to compare the usefulness of IVUS-FFR and IVUS-derived MLA for functional assessment.Methods and Results:We retrospectively analyzed 50 lesions in 48 patients with coronary stenosis who underwent IVUS and FFR simultaneously. IVUS-FFR was calculated using our original algorithm and fluid dynamics. Mean percent diameter stenosis determined on quantitative coronary angiography and on FFR was 56.4±10.7 and 0.69±0.08, respectively. IVUS-FFR had a stronger linear correlation with FFR (R=0.78, P<0.001; root mean square error, 0.057 FFR units) than with IVUS-derived MLA (R=0.43, P=0.002). CONCLUSIONS: IVUS-FFR may be a more valuable method to identify myocardial ischemia, compared with IVUS-derived MLA.

Incremental value of left atrial active function measured by speckle tracking echocardiography in patients with hypertrophic cardiomyopathy.

PURPOSE: Hypertrophic cardiomyopathy (HCM) impairs left ventricular (LV) diastolic function leading to left atrial (LA) dilatation. Because Doppler echocardiography cannot accurately assess LV diastolic function in hearts with heterogeneous hypertrophy, assessment of LA function might be useful for risk stratification of patients with HCM. This study aimed to elucidate the impact of LA function on outcome in patients with patients. METHODS: Seventy-six patients with HCM who underwent echocardiographic and cardiac magnetic resonance imaging were retrospectively enrolled. Twenty-six control subjects were also included. Using speckle tracking echocardiography, LA function was divided into active and passive strain indices based on the timing of the second positive peak of LA strain rate that occurred during LV systole. RESULTS: Left atrial strain indices of active and passive function were significantly impaired concomitantly with increased LA volume index in HCM patients compared with controls. During follow-up (2.6 ± 1.7 years), 14 patients with HCM developed cardiac events (heart failure hospitalization or atrial fibrillation). The association of LA active strain with cardiac events was independent of and incremental to clinical and echocardiographic parameters (age, gender, E/e', LV global longitudinal strain, and LA volume index) in sequential models. Cardiac events were more frequent in HCM patients with LA active strain <20.3% than with active strain ≥20.3% (P = .01). CONCLUSION: Loss of LA active function was associated with increased cardiac events in patients with HCM.

A Novel Truncating LMNA Mutation in Patients with Cardiac Conduction Disorders and Dilated Cardiomyopathy.

The cardiac phenotype of laminopathies is characterized by cardiac conduction disorders (CCDs) and dilated cardiomyopathy (DCM). Although laminopathies have been considered monogenic, they exhibit a remarkable degree of clinical variability. This case series aimed to detect the causal mutation and to investigate the causes of clinical variability in a Japanese family with inherited CCD and DCM.Of the five family members investigated, four had either CCD/DCM or CCD alone, while one subject had no cardiovascular disease and acted as a normal control. We performed targeted resequencing of 174 inherited cardiovascular disease-associated genes in this family and pathological mutations were confirmed using Sanger sequencing. The degree of clinical severity and variability were also evaluated using long-term medical records. We discovered a novel heterozygous truncating lamin A/C (LMNA) mutation (c.774delG) in all four subjects with CCD. Because this mutation was predicted to cause a frameshift mutation and premature termination (p.Gln258HisfsTer222) in LMNA, we believe that this LMNA mutation was the causal mutation in this family with CCD and laminopathies. In addition, gender-specific intra-familiar clinical variability was observed in this Japanese family where affected males exhibited an earlier onset of CCD and more severe DCM compared to affected females. Using targeted resequencing, we discovered a novel truncating LMNA mutation associated with CCD and DCM in this family characterized by gender differences in clinical severity in LMNA carriers. Our results suggest that in patients with laminopathy, clinical severity may be the result of multiple factors.

Three-dimensional maximum principal strain using cardiac computed tomography for identification of myocardial infarction.

OBJECTIVES: To evaluate the feasibility of three-dimensional (3D) maximum principal strain (MP-strain) derived from cardiac computed tomography (CT) for detecting myocardial infarction (MI). METHODS: Forty-three patients who underwent cardiac CT and magnetic resonance imaging (MRI) were retrospectively selected. Using the voxel tracking of motion coherence algorithm, the peak CT MP-strain was measured using the 16-segment model. With the trans-mural extent of late gadolinium enhancement (LGE) and the distance from MI, all segments were classified into four groups (infarcted, border, adjacent, and remote segments); infarcted and border segments were defined as MI with LGE positive. Diagnostic performance of MP-strain for detecting MI was compared with per cent systolic wall thickening (%SWT) assessed by MRI using receiver-operating characteristic curve analysis at a segment level. RESULTS: Of 672 segments excluding16 segments influenced by artefacts, 193 were diagnosed as MI. Sensitivity and specificity of peak MP-strain to identify MI were 81 % [95 % confidence interval (95 % CI): 74-88 %] and 86 % (81-92 %) compared with %SWT: 76 % (60-95 %) and 68 % (48-84 %), respectively. The area under the curve of peak MP-strain was superior to %SWT [0.90 (0.87-0.93) vs. 0.80 (0.76-0.83), p < 0.05]. CONCLUSIONS: CT MP-strain has a potential to provide incremental value to coronary CT angiography for detecting MI. KEY POINTS: • CT MP-strain allows for three-dimensional assessment of regional cardiac function. • CT-MP strain has high diagnostic accuracy for detecting myocardial infarction. • CT-MP strain may assist in tissue characterisation of myocardium assessed by LGE-MRI. • CT-MP strain provides incremental values to coronary CTA for detecting myocardial infarction.

Differentiation of myocardial ischemia and infarction assessed by dynamic computed tomography perfusion imaging and comparison with cardiac magnetic resonance and single-photon emission computed tomography.

OBJECTIVES: To evaluate the feasibility of myocardial blood flow (MBF) by computed tomography from dynamic CT perfusion (CTP) for detecting myocardial ischemia and infarction assessed by cardiac magnetic resonance (CMR) or single-photon emission computed tomography (SPECT). METHODS: Fifty-three patients who underwent stress dynamic CTP and either SPECT (n = 25) or CMR (n = 28) were retrospectively selected. Normal and abnormal perfused myocardium (ischemia/infarction) were assessed by SPECT/CMR using 16-segment model. Sensitivity and specificity of CT-MBF (mL/g/min) for detecting the ischemic/infarction and severe infarction were assessed. RESULTS: The abnormal perfused myocardium and severe infarction were seen in SPECT (n = 90 and n = 19 of 400 segments) and CMR (n = 223 and n = 36 of 448 segments). For detecting the abnormal perfused myocardium, sensitivity and specificity were 80 % (95 %CI, 71-90) and 86 % (95 %CI, 76-91) in SPECT (cut-off MBF, 1.23), and 82 % (95 %CI, 76-88) and 87 % (95 %CI, 80-92) in CMR (cut-off MBF, 1.25). For detecting severe infarction, sensitivity and specificity were 95 % (95 %CI, 52-100) and 72 % (95 %CI, 53-91) in SPECT (cut-off MBF, 0.92), and 78 % (95 %CI, 67-97) and 80 % (95 %CI, 58-86) in CMR (cut-off MBF, 0.98), respectively. CONCLUSIONS: Dynamic CTP has a potential to detect abnormal perfused myocardium and severe infarction assessed by SPECT/CMR using comparable cut-off MBF. KEY POINTS: • CT-MBF accurately reflects the severity of myocardial perfusion abnormality. • CT-MBF provides good diagnostic accuracy for detecting myocardial perfusion abnormalities. • CT-MBF may assist in stratifying severe myocardial infarction in abnormal perfusion myocardium.

Optimal Scan Time for Single-Phase Myocardial Computed Tomography Perfusion to Detect Myocardial Ischemia　- Derivation Cohort From Dynamic Myocardial Computed Tomography Perfusion.

BACKGROUND: Single-phase myocardial computed tomography perfusion (CTP) is useful for detecting myocardial ischemia, but determining the optimal scan time is difficult. The present study evaluated this by analyzing dynamic CTP data.Methods and Results:We retrospectively selected 32 patients, all of whom had undergone stress dynamic CTP and magnetic resonance myocardial perfusion imaging (MR-MPI). Myocardial ischemia was assessed by MR-MPI using the 16-segment model. Whole-heart dynamic CTP data were acquired for 30 consecutive heartbeats without spatial or temporal gaps using a wide-detector CT, and redistributed into 11 series of single-phase CTP acquired from -2 s to 8 s from the time of maximal enhancement (Tmax) in the ascending aorta. Single-phase CTP images were visually assessed at the segment level, and diagnostic performance of single-phase CTP images for detecting myocardial ischemia was compared with dynamic CTP. Of 512 segments, 177 segments (35%) were diagnosed as ischemic by MR-MPI. The diagnostic accuracy of single-phase CTP acquired at 2-6 s from Tmax in the ascending aorta (median 86%, range 84-87%) was comparable to that of dynamic CTP. CONCLUSIONS: The optimal scan time for detecting myocardial ischemia with single-phase CTP was at 2-6 s from Tmax in the ascending aorta. (Circ J 2016; 80: 2506-2512).

Clinical Significance of Peripheral Endothelial Function for Left Atrial Blood Stagnation in Nonvalvular Atrial Fibrillation Patients With Low-to-Intermediate Stroke Risk.

BACKGROUND: In patients who have atrial fibrillation (AF) with CHADS2score of 0-1 (categorized as low-to-intermediate risk), there is little information on stratifying the risk of stroke. This study aimed to determine whether impaired endothelial function assessed by reactive hyperemia-peripheral arterial tonometry (RH-PAT) predicted left atrial blood stagnation in these patients. METHODS AND RESULTS: We enrolled 81 consecutive patients with nonvalvular AF. The reactive hyperemia index (RHI) was measured using RH-PAT. Transesophageal echocardiography was performed to determine spontaneous echo contrast (SEC) before direct-current cardioversion or radiofrequency catheter ablation. SEC was found in 49 patients (60%). The RHI was significantly lower in patients with than without SEC. Multivariate analysis demonstrated that RHI was one of the independent determinants of SEC (OR per 0.1, 1.26; 95% CI, 1.11-1.49; P=0.002) in all patients. In addition, RHI was a significant determinant of SEC (AUC, 0.73; 95% CI, 0.63-0.89; P=0.0017) in patients with low-to-intermediate risk. At an RHI cut-off <1.62, the sensitivity and specificity for the identification of patients with SEC were 58% and 89%, respectively. CONCLUSIONS: Impaired endothelial function assessed by RH-PAT might help to predict the presence of SEC in patients with low-to-intermediate risk of stroke. (Circ J 2016; 80: 2117-2123).

Clinical Utility of Atrial Electromechanical Conduction Time Measured with Speckle Tracking Echocardiography after Catheter Ablation in Patients with Atrial Fibrillation: A Validation Study with Electroanatomical Mapping.

PURPOSE: Our recent report demonstrated that atrial electromechanical conduction time (EMT-ε) measured with speckle tracking echocardiography could predict cardiac events in patients with pathological left ventricular hypertrophy. This study aimed to validate EMT-ε by comparison with electroanatomical mapping and to investigate the clinical utility of EMT-ε in patients with atrial fibrillation (AF) undergoing catheter ablation. METHODS: Forty-six patients with preserved LV ejection fraction (LVEF ≥ 50%) undergoing pulmonary vein isolation (PVI) for AF were studied. Atrial electrical conduction delay was determined by measuring atrial electrical activation time (EAT) using three-dimensional electroanatomical mapping just after PVI. Echocardiographic parameters were acquired within 24 hours and at 6 months after PVI. The study also included 10 control subjects. RESULTS: AF patients had a larger left atrial (LA) volume index (LAVI) and more prolonged EMT-ε compared with control subjects. According to the validation study, EAT was closely related to EMT-ε and a', and this association was independent of LAVI and the presence of persistent AF (EMT-ε: R(2) = 0.342, P < 0.0001, a': R(2) = 0.337, P < 0.0001). At 6 months after PVI, LAVI and EMT-ε were significantly improved. During continued follow-up beyond 6 months (total follow-up, 26 ± 12 months), the EMT-ε shortening at 6 months after PVI was significantly greater in AF-free patients than patients with AF recurrence. CONCLUSIONS: This study suggested that the EMT-ε could be a useful echocardiographic marker of LA electromechanical abnormalities in patients with AF.

Association Between Genetic Variation in the SCN10A Gene and Cardiac Conduction Abnormalities in Patients With Hypertrophic Cardiomyopathy.

Arrhythmias are associated with reduced quality of life and poor prognosis in patients with hypertrophic cardiomyopathy (HCM). Recent genome-wide association studies revealed that a nonsynonymous single nucleotide polymorphism, rs6795970, in the SCN10A gene was associated with the PR interval. We examined whether the PR prolonging allele (A allele) in the SCN10A gene may be associated with cardiac conduction abnormalities in HCM patients.We genotyped the polymorphism in 149 HCM patients. Conduction abnormalities were defined as first-degree heart block, bundle-branch block, and bifascicular heart block. Patients were divided into two groups: group A consisted of 122 patients (82%) without a conduction abnormality; and group B consisted of 27 patients (18%) with one or more cardiac conduction abnormalities. The frequency distribution of the SCN10A genotypes (G/G, G/A, and A/A) among the patients with HCM was 71%, 26%, and 3%, respectively. A cardiac conduction abnormality was documented in 9% with G/G and 40% with G/A or A/A. There was a significant difference in the genotype distribution between the two groups (P = 0.0002). In the dominant A allele model, there was a significant difference in genotypes between the two groups (P < 0.0001). In addition, the A allele remained significant after adjusting for other covariates in a multivariate model (odds ratio = 6.30 [95% confidence interval: 2.24 to 19.09], P = 0.0005).The rs6795970 in the SCN10A gene, which is reported to carry a high risk of heart block, might be associated with cardiac conduction abnormalities in HCM patients.

Pseudo-hyperacute T Waves in a Giant Hiatal Hernia.

An 89-year-old woman with a giant hiatal hernia complained of persistent chest pain. An electrocardiogram (ECG) showed hyperacute T waves, suggesting the early phase of ST-elevation myocardial infarction. After endoscopic drainage for hiatal hernia, the chest pain disappeared, and the ECG abnormalities resolved. The present case illustrates that compression of the heart by a giant hiatal hernia can induce T wave elevation mimicking acute coronary syndrome.

Feasibility of four-dimensional similarity filter for radiation dose reduction in dynamic myocardial computed tomography perfusion imaging.

Rationale and objectives: We aimed to evaluate the impact of four-dimensional noise reduction filtering using a four-dimensional similarity filter (4D-SF) on radiation dose reduction in dynamic myocardial computed tomography perfusion (CTP). Materials and methods: Forty-three patients who underwent dynamic myocardial CTP using 320-row computed tomography (CT) were included in the study. The original images were reconstructed using iterative reconstruction (IR). Three different CTP datasets with simulated noise, corresponding to 25%, 50%, and 75% reduction of the original dose (300 mA), were reconstructed using a combination of IR and 4D-SF. The signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) were assessed, and CT-derived myocardial blood flow (CT-MBF) was quantified. The results were compared between the original and simulated images with radiation dose reduction. Results: The median SNR (first quartile-third quartile) at the original, 25%-, 50%-, and 75%-dose reduced-simulated images with 4D-SF was 8.3 (6.5-10.2), 16.5 (11.9-21.7), 15.6 (11.0-20.1), and 12.8 (8.8-18.1) and that of CNR was 4.4 (3.2-5.8), 6.7 (4.6-10.3), 6.6 (4.3-10.1), and 5.5 (3.5-9.1), respectively. All the dose-reduced-simulated CTPs with 4D-SF had significantly higher image quality scores in SNR and CNR than the original ones (25%-, 50%-, and 75%-dose reduced vs. original images, p < 0.05, in each). The CT-MBF in 75%-dose reduced-simulated CTP was significantly lower than 25%-, 50%- dose-reduced-simulated, and original CTPs (vs. 75%-dose reduced-simulated images, p < 0.05, in each). Conclusion: 4D-SF has the potential to reduce the radiation dose associated with dynamic myocardial CTP imaging by half, without impairing the robustness of MBF quantification.