Microvascular Dysfunction in Patients with Idiopathic Dilated Cardiomyopathy: Quantitative Assessment with Phase Contrast Cine MR Imaging of the Coronary Sinus.

PURPOSE: The purposes of this study were to compare global coronary flow reserve (CFR) between patients with idiopathic dilated cardiomyopathy (DCM) and risk-matched controls using cardiac MRI (CMR), and to evaluate the relationship between global CFR and CMR left ventricular (LV) parameters. METHODS: Twenty-six patients with DCM and 26 risk-matched controls who underwent comprehensive CMR examination, including stress-rest coronary sinus flow measurement by phase contrast (PC) cine CMR were retrospectively studied. LV peak global longitudinal, radial, and circumferential strains (GLS, GRS, and GCS) were determined by feature tracking. RESULTS: Patients with DCM had significantly lower global CFR compared with the risk-matched controls (2.87 ± 0.86 vs. 4.03 ± 1.47, P = 0.001). Among the parameters, univariate linear regression analyses revealed significant correlation of global CFR with LV end-diastolic volume index (r = -0.396, P = 0.045), LV mass index (r = -0.461, P = 0.018), GLS (r = -0.558, P = 0.003), and GRS (r = 0.392, P = 0.047). Multiple linear regression analysis revealed GLS as the only independent predictor of global CFR (standardized ß = -0.558, P = 0.003). CONCLUSION: Global CFR was significantly impaired in patients with idiopathic DCM and independently associated with LV GLS, suggesting that microvascular dysfunction may contribute to deterioration of LV function in patients with idiopathic DCM.

Assessment of Pseudocoarctation of the Aorta with Saccular Aneurysms by Four-Dimensional Flow Magnetic Resonance Imaging and Histological Analysis.

In this study, we present the case of a 21-year-old woman with pseudocoarctation of the aorta with saccular aneurysms that were evaluated by four-dimensional flow magnetic resonance imaging and histological analysis. We observed complete occupation of the aneurysm sacs by vortex flow and high peak wall shear stress in the proximal region of the kinked aorta. The aortic replacement was performed for the thoracic aortic aneurysms and the clinical course was uneventful. The aneurysms were histopathologically diagnosed as pseudoaneurysms based on the disappearance of all three layers and their replacement with collagen-rich connective tissues. These findings indicate that abnormal flow dynamics and the resulting abnormal shear stress in the aorta may play central roles in the formation and development of a saccular aneurysm.

Quantification of extracellular volume fraction by cardiac computed tomography for noninvasive assessment of myocardial fibrosis in hemodialysis patients.

Extent of myocardial fibrosis in hemodialysis patients has been associated with poor prognosis. Myocardial extracellular volume (ECV) quantification using contrast enhanced cardiac computed tomography (CT) is a novel method to determine extent of myocardial fibrosis. Cardiac CT-based myocardial ECV in hemodialysis patients with those of propensity-matched non-hemodialysis control subjects were compared. Twenty hemodialysis patients (mean age, 67.4 ± 9.6 years; 80% male) and 20 propensity-matched non-hemodialysis controls (mean age, 66.3 ± 9.1 years; 85% male) who underwent comprehensive cardiac CT consisted of calcium scoring, coronary CT angiography, stress perfusion CT and delayed enhancement CT were evaluated. Myocardial ECV was significantly greater in the hemodialysis group than in the control group (33.8 ± 4.7% versus 26.6 ± 2.9%; P < 0.0001). In the hemodialysis group, modest correlation was evident between myocardial ECV and left atrial volume index (r = 0.54; P = 0.01), while there was no correlation between myocardial ECV and other cardiac parameters including left ventricular mass index and severity of myocardial ischemia. Cardiac CT-based myocardial ECV may offer a potential imaging biomarker for myocardial fibrosis in HD patients.

Echocardiographic assessment of cardiac structure and function in chronic renal disease.

Chronic kidney disease (CKD) is a global health problem and is independently associated with increased risk for cardiovascular disease (CVD). The presence and severity of CKD is strongly related to the progression of coronary atherosclerosis, ventricular hypertrophy, myocardial fibrosis, valvular calcification, and cardiac conduction system abnormalities. Echocardiography plays a major role in the assessment of structural and functional cardiac abnormalities in CKD including abnormal left-ventricular (LV) geometry, LV diastolic dysfunction, valvular disease, and left atrial dilatation, which are very frequently present especially in patients with end-stage renal disease.

Combined Assessment of Stress Myocardial Perfusion Cardiovascular Magnetic Resonance and Flow Measurement in the Coronary Sinus Improves Prediction of Functionally Significant Coronary Stenosis Determined by Fractional Flow Reserve in Multivessel Disease.

BACKGROUND: Recent studies using stress-rest perfusion cardiovascular magnetic resonance (CMR) demonstrated a close correlation between myocardial ischemia and reduced fractional flow reserve (FFR). However, its diagnostic concordance may be reduced in patients with multivessel disease. We sought to evaluate the concordance of adenosine stress-rest perfusion CMR for predicting reduced FFR, and to determine the additive value of measuring global coronary flow reserve (CFR) in the coronary sinus in multivessel disease. METHODS AND RESULTS: Ninety-six patients with angiographic luminal narrowing >50% underwent comprehensive CMR study and FFR measurements in 139 coronary vessels. FFR <0.80 was considered hemodynamically significant. Global CFR was quantified as the ratio of stress-rest coronary sinus flow measured by phase-contrast cine CMR. In 25 patients with single-vessel disease, visual assessment of perfusion CMR yielded high diagnostic concordance for predicting flow-limiting stenosis, with the area under receiver operating characteristic curve of 0.93 on a per-patient basis. However, in 71 patients with multivessel disease, perfusion CMR underestimated flow-limiting stenosis, resulting in the reduced area under receiver operating characteristic curve of 0.74. When CFR of <2.0 measured in the coronary sinus was considered as global myocardial ischemia, combined assessment provided correct reclassifications in 7 patients with false-negative myocardial ischemia, and improved the diagnostic concordance to 92% sensitivity and 73% specificity with the area under receiver operating characteristic curve of 0.88 (95% confidence interval, 0.80%-0.97%, P=0.002). CONCLUSIONS: Visual analysis of stress-rest perfusion CMR has limited concordance with FFR in patients with multivessel disease. Multiparametric CMR integrating stress-rest perfusion CMR and flow measurement in the coronary sinus is useful for detecting reduced FFR in multivessel disease.

Echocardiographic Assessment of Cardiac Structural and Functional Abnormalities in Patients With End-Stage Renal Disease Receiving Chronic Hemodialysis.

BACKGROUND: The aim of this study was to assess the echocardiographic characteristics of chronic hemodialysis (HD) patients with end-stage renal disease (ESRD) in a multicenter prospective cohort study.Methods and Results:Three hundred and fifteen patients with ESRD (67.9±10.6 years, 47.6% male) on chronic HD for ≥1 year were examined on transthoracic echocardiography, including Doppler-derived aortic valve area (AVA) measurement. Only 11.5% and 3.4% of all patients had normal left ventricular (LV) geometry and normal LV filling pattern, respectively. The majority of patients had aortic and mitral valvular calcification, and approximately 50% of all 315 patients had aortic valve narrowing with AVA <2.0 cm2. Patients were divided into 3 groups according to AVA index tertile: group 1, highest tertile; group 2, middle tertile; and group 3, lowest tertile. Group 3 was older, had a greater cardiothoracic ratio on chest X-ray, higher plasma brain natriuretic peptide and total LV afterload, and lower stroke volume index than the other 2 groups. Age and intact parathyroid hormone (PTH) level were independently associated with low AVA index. CONCLUSIONS: Patients with ESRD on chronic HD have a high prevalence of cardiac structural and functional abnormalities including calcified aortic sclerosis. High age and PTH were associated with aortic valve narrowing in these patients.

Native T1 Mapping and Extracellular Volume Mapping for the Assessment of Diffuse Myocardial Fibrosis in Dilated Cardiomyopathy.

OBJECTIVES: The purpose of this study was to examine the histological correlation of native myocardial T1 and extracellular volume fraction (ECV) measurement at 3-T for the assessment of diffuse pathological changes in the myocardial tissue, including myocardial fibrosis and extracellular space in dilated cardiomyopathy (DCM). BACKGROUND: Cardiac magnetic resonance T1 techniques allow the quantification of diffuse myocardial fibrosis. However, there are no definitive head-to-head studies of native T1 versus ECV for the detection, quantification, and characterization of pathological changes in the myocardial tissue in DCM by using histological samples for confirmation. METHODS: A total of 36 subjects with DCM (31 men, mean age 56 ± 16 years) underwent pre- and post-contrast T1 mapping as well as late gadolinium enhancement (LGE) cardiac magnetic resonance at 3-T. Biopsy samples were used for the quantification of collagen volume fraction using picrosirius red staining and an extracellular space component from hematoxylin and eosin-stained myocardium. RESULTS: Nonischemic LGE was observed in 14 of 36 patients. Although patients with LGE had significantly greater biopsy-proven collagen volume fraction than those without LGE (21 ± 12% vs. 11 ± 8%; p < 0.01), there was substantial overlap of collagen volume fraction values between patients with and without LGE. Both native T1 value and ECV were similarly and significantly associated with biopsy-proven collagen volume fraction (r = 0.77 and r = 0.66, respectively; p < 0.05). Furthermore, ECV had a strong correlation with the biopsy-proven extracellular space component (r = 0.86), whereas native T1 had only a moderate correlation (r = 0.55). Interobserver and intraobserver reproducibility for native T1 and ECV were 0.89, 0.95, 0.96, and 0.98, respectively. CONCLUSIONS: Native T1 exhibited comparable ability as ECV measurement in the detection and quantification of histological collagen volume fraction, with high reproducibility, and therefore diffuse myocardial fibrosis in DCM may be reliably assessed by native T1 mapping without the administration of gadolinium contrast agent. In addition, cardiac magnetic resonance-derived ECV showed excellent agreement with histological extracellular space.

The Speckle Tracking Imaging for the Assessment of Cardiac Resynchronization Therapy (START) study.

BACKGROUND: We sought to identify the feasibility of speckle tracking echocardiography (STE) to predict cardiac resynchronization therapy (CRT) responders in a prospective multicenter study. METHODS AND RESULTS: Patients who were newly implanted with a CRT device were enrolled. Time (T) from QRS to maximum peak radial and circumferential strain (CS) in 6 segments on the left ventricular (LV) short-axis plane, and to the maximum peak of longitudinal strain in 18 segments on 3 apical LV planes was measured (Tmax). In segments with multiple peaks on the time-strain curves, time to the first peak (Tfirst) was also assessed. Difference in T between the earliest and latest segment and standard deviation (SD) of T in each strain component were assessed. CRT responders were defined as having LV end-systolic volume reduction >15% at 6 months after CRT. Clinical outcomes were assessed with a composite endpoint of death from cardiac causes or unplanned hospitalization for heart failure. Among 180 patients, 109 patients were identified as responders. Tfirst-SD of CS >116 ms was selected as the best independent predictor of CRT responders (P<0.001, hazard ratio=9.83, 95% confidence interval 3.78-25.6). In addition, Tfirst-SD of CS was associated with the clinical endpoints. CONCLUSIONS: This prospective multicenter study revealed the high feasibility of dyssynchrony assessment by STE, which may improve the ability to predict CRT responders.

Altered coronary endothelial function in young smokers detected by magnetic resonance assessment of myocardial blood flow during the cold pressor test.

Endothelial dysfunction is a key element in early atherogenesis. The purposes of this study were to evaluate the feasibility of magnetic resonance (MR) assessment of altered myocardial blood flow (MBF) in response to the cold pressor test (CPT) and to determine if coronary endothelial dysfunction in young smokers can be detected with this noninvasive approach. Fourteen healthy non-smokers (31 ± 6 years) and 12 smokers (34 ± 8 years) were studied. Breath-hold phase-contrast cine MR imaging (PC-MRI) of the coronary sinus (CS) were obtained at rest and during the CPT. MBF was measured as CS flow divided by left ventricle mass and the rate pressure product. In non-smokers, MBF was 0.88 ± 0.19 ml/min/g at rest and significantly increased to 1.13 ± 0.26 ml/min/g during the CPT (P = 0.0001). In smokers, MBF was 0.94 ± 0.26 ml/min/g at rest and 0.96 ± 0.30 ml/min/g during the CPT (P = 0.73). ΔMBF (MBF during the CPT-MBF at rest) was significantly reduced in smokers compared with non-smokers (0.02 ± 0.20 vs. 0.26 ± 0.18 ml/min/g, P = 0.005). The intra-class correlation coefficient between measurements by two observers was 0.90 for ΔMBF. A significant reduction in MBF response to CPT was demonstrated in young smokers with PC-MRI at 1.5 T. This noninvasive method has great potential for assessment of coronary endothelial function.

Quantitative assessment of myocardial strain with displacement encoding with stimulated echoes MRI in patients with coronary artery disease.

To determine the diagnostic performance and reproducibility of strain assessment with displacement encoding with stimulated echoes (DENSE) cardiovascular magnetic resonance (CMR) in identifying contractile abnormalities in myocardial segments with late gadolinium enhancement (LGE). DENSE CMR was obtained on short-axis planes of the left ventricle (LV) in 24 patients with suspected coronary artery disease. e1 and e2 strains of LV wall were quantified. Cine MRI was acquired to determine percent systolic wall thickening (%SWT), followed by (LGE) CMR. The diagnostic performance of e1, e2 and %SWT for predicting the presence of LGE was evaluated by receiver operating characteristics (ROC) analysis. Myocardial scar on LGE CMR was observed in 91 (24 %) of 384 segments. The area under ROC curve for predicting the segments with LGE was 0.874 by e1, 0.916 by e2 and 0.828 by %SWT (p = 0.001 between e2 and %SWT). Excellent inter-observer reproducibility was found for strain [Intraclass correlation coefficient (ICC) = 0.962 for e1, 0.955 for e2] as compared with %SWT (ICC = 0.790). DENSE CMR can be performed as a part of routine CMR study and allows for quantification of myocardial strain with high inter-observer reproducibility. Myocardial strain, especially e2 is useful in detecting altered abnormal systolic contraction in the segments with myocardial scar.

Improving drug adherence using fixed combinations caused beneficial treatment outcomes and decreased health-care costs in patients with hypertension.

We enrolled 196 patients with hypertension who were already being treated with free-drug combinations of angiotensin-II receptor blocker (ARB) and amlodipine. The free-drug combinations of ARB and amlodipine were replaced with the same dose of the fixed-dose combinations. The average home blood pressure (BP) in all patients receiving fixed-dose combinations was significantly lower than those receiving free-drug combinations (131 ± 10/75 ± 8 vs. 136 ± 11/77 ± 9 mm Hg, P < .01) accompanied with increasing drug adherence. After lowering BP by fixed-dose combinations, the costs for medications decreased by 31% over the 3 months.

Assessment of left ventricular systolic function in patients with chronic atrial fibrillation and dilated cardiomyopathy using the ratio of preceding to prepreceding R-R intervals.

The objective of this study was to determine the relation between left ventricular (LV) systolic function and the ratio of preceding (RR1) to prepreceding (RR2) R-R intervals in patients with chronic atrial fibrillation (AF) and dilated cardiomyopathy. LV systolic function (Emax) was examined using a conductance catheter with a micromanometer in 13 patients with chronic AF and dilated cardiomyopathy. We calculated Emax as a load-independent index of LV contractility and compared it with RR1, RR2, and the ratio of RR1/RR2. We analyzed 50+/-13 cardiac cycles (range 18-61) in each patient. Average heart rate was 80+/-13 beats/min, and ejection fraction over all cardiac cycle in each patient measured by conductance catheter was 31+/-8%. Emax was positively correlated with RR1 and RR1/RR2 in all patients, and negatively correlated with RR2 in all patients. In each patient, correlation coefficients of Emax with RR1/RR2 were greater than those with either RR1 or RR2. Furthermore, Emax at RR1/RR2=1 in the linear regression line reflected average Emax over all cardiac cycles in each patient. In conclusion, we have shown that LV contractility correlated positively with RR1/RR2 in patients with chronic AF and dilated cardiomyopathy, and LV contractility at RR1/RR2=1 represents the average value of contractility over all cardiac cycles.

Second-generation tissue Doppler with angle-corrected color-coded wall displacement for quantitative assessment of regional left ventricular function.

To test the hypothesis that a new tissue Doppler (TD) approach using angle-correction and transformation of velocity data to color-coded displacement data may objectively quantify regional left ventricular function, in vitro experiments were first performed with an oscillating echo target precisely controlled by a microstepping motor. Displacement varied from 1 to 15 mm (60 to 130 cycles/min) at angles of 0 degrees and 45 degrees to the echo transducer. Custom software transformed TD data to displacement data. Sixty-five subjects were then studied: 35 with wall motion abnormalities and 30 normal controls. Results were compared with independent visual assessment and caliper measurements of endocardial excursion from gray-scale images. In vitro displacement imaging strongly correlated with true displacement (r = 0.99, p <0.0001). In humans, peak transmural displacement discriminated normal results (6.3 +/- 3.2 mm) from hypokinesia (2.7 +/- 1.8 mm, p <0.05), akinesia (0.4 +/- 1.2 mm, p <0.05) from hypokinesia, and dyskinesia (-1.9 +/- 1.2 mm, p <0.05) from akinesia. Normal subendocardial displacement was 5.9 +/- 2.9 versus 4.0 +/- 3.9 mm in the epicardial layer (p <0.01). This displacement gradient was absent in abnormal segments. Displacement data correlated with endocardial excursion by calipers (parasternal views: r = 0.86, all views: r = 0.79, both p <0.0001). Overall accuracy of displacement imaging was 82% (kappa = 0.71) versus 66% (kappa = 0.43) for visual assessment with caliper data as the standard of reference. Angle-corrected displacement imaging was superior to routine visual assessment and is a promising new method to quantify regional left ventricular function.