Myocardial bridging in obstructive hypertrophic cardiomyopathy: a risk factor for myocardial fibrosis.

BACKGROUND:Myocardial bridging (MB) is common in patients with hypertrophic cardiomyopathy (HCM). There are sparse data on the impact of MB on myocardial fibrosis in HCM. This study was designed to evaluate the relationship between MB and myocardial fibrosis in patients with obstructive HCM.METHODS:In this cohort study, retrospective data were collected from a high-volume HCM center. Patients with obstructive HCM who underwent septal myectomy and preoperative cardiac magnetic resonance (CMR) were screened from 2011 to 2018.RESULTS:Finally, 492 patients were included in this study, with an average age of 45.7 years. Of these patients, 76 patients had MB. MB occurred mostly in the left anterior descending artery (73/76). The global extent of late gadolinium enhancement (LGE) was correlated with the degree of systolic compression (r = 0.33, p = 0.003). Multivariable linear regression analysis revealed that the degree of systolic compression was an independent risk factor for LGE (β = 0.292, p = 0.007). The LGE fraction of basal and mid anteroseptal segments in patients with severe MB (compression ratio ≥ 80%) was significantly greater than that in patients with mild to moderate MB (compression ratio < 80%). During a median follow-up of 28 (IQR: 15-52) months, 15 patients died. Kaplan-Meier analysis did not identify differences in all-cause death (log-rank p = 0.63) or cardiovascular death (log-rank p = 0.72) between patients undergoing MB-related surgery and those without MB.CONCLUSIONS:MB with severe systolic compression was significantly associated with a high extent of fibrosis in patients with obstructive HCM. Concomitant myotomy or coronary artery bypass grafting might provide excellent survival similar to that of patients without MB. Identification of patients with severe MB and providing comprehensive management might help improve the prognosis of patients with HCM.

Association between QRS voltages and amyloid burden in patients with cardiac amyloidosis.

Association between left atrial myopathy and sarcomere mutation in patients with hypertrophic cardiomyopathy: insights into left atrial strain by MRI feature tracking.

OBJECTIVES:Left atrial (LA) myopathy, characterized by LA enlargement and mechanical dysfunction, is associated with worse prognosis in hypertrophic cardiomyopathy (HCM) while the impact of sarcomere mutation on LA myopathy remains unclear. We aimed to assess the association between LA myopathy and sarcomere mutation and to explore the incremental utility of LA strain in mutation prediction.METHODS:A total of 105 consecutive HCM patients (mean age 47.8 ± 11.9 years, 71% male) who underwent HCM-related gene screening and cardiac MRI were retrospectively enrolled. LA volume, ejection fraction and strain indices in reservoir, conduit, and booster-pump phases were investigated respectively.RESULTS:Fifty mutation-positive patients showed higher LA maximal volume index (59.4 ± 28.2 vs 43.8 ± 18.1 mL/m2, p = 0.001), lower reservoir (21.3 ± 7.9 vs 26.2 ± 6.6%, p < 0.001), and booster-pump strain (12.1 ± 5.4 vs 17.1 ± 5.0%, p < 0.001) but similar conduit strain (9.2 ± 4.5 vs 9.1 ± 4.5%, p = 0.909) compared with mutation-negative patients. In multivariate logistic regression, LA booster-pump strain was associated with sarcomere mutation (odds ratio = 0.86, 95% confidence interval: 0.77-0.96, p = 0.010) independent of maximal wall thickness, late gadolinium enhancement, and LA volume. Furthermore, LA booster-pump strain showed incremental value for mutation prediction added to Mayo II score (AUC 0.798 vs 0.709, p = 0.024).CONCLUSIONS:In HCM, mutation-positive patients suffered worse LA enlargement and worse reservoir and booster-pump functions. LA booster-pump strain was a strong factor for sarcomere mutation prediction added to Mayo II score.CLINICAL RELEVANCE STATEMENT:The independent association between sarcomere mutation and left atrial mechanical dysfunction provide new insights into the pathogenesis of atrial myopathy and is helpful to understand the adverse prognosis regarding atrial fibrillation and stroke in mutation-positive patients.KEY POINTS:• In patients with hypertrophic cardiomyopathy, left atrial (LA) reservoir and booster-pump function, but not conduit function, were significantly impaired in mutation-positive patients compared with mutation-negative patients. • LA booster-pump strain measured by MRI-derived feature tracking is feasible to predict sarcomere mutation with high incremental value added to Mayo II score.

Long-term outcomes prediction in diabetic heart failure with preserved ejection fraction by cardiac MRI.

OBJECTIVES:We aimed to explore imaging features including tissue characterization and myocardial deformation in diabetic heart failure with preserved ejection fraction (HFpEF) patients by magnetic resonance imaging (MRI) and investigate its prognostic value for adverse outcomes.MATERIALS AND METHODS:Patients with HFpEF who underwent cardiac MRI between January 2010 and December 2016 were enrolled. Feature-tracking (FT) analysis and myocardial fibrosis were assessed by cardiac MRI. Cox proportional regression analysis was performed to determine the association between MRI variables and primary outcomes. Primary outcomes were all-cause death or heart failure hospitalization during the follow-up period.RESULTS:Of the 335 enrolled patients with HFpEF, 191 had diabetes mellitus (DM) (mean age: 58.7 years ± 10.8; 137 men). During a median follow-up of 10.2 years, 91 diabetic HFpEF and 56 non-diabetic HFpEF patients experienced primary outcomes. DM was a significant predictor of worse prognosis in HFpEF. In diabetic HFpEF, the addition of conventional imaging variables (left ventricular ejection fraction, left atrial volume index, extent of late gadolinium enhancement (LGE)) and global longitudinal strain (GLS) resulted in a significant increase in the area under the receiver operating characteristic curve (from 0.693 to 0.760, p < 0.05). After adjustment for multiple clinical and imaging variables, each 1% worsening in GLS was associated with a 9.8% increased risk of adverse events (p = 0.004).CONCLUSIONS:Diabetic HFpEF is characterized by more severely impaired strains and myocardial fibrosis, which is identified as a high-risk HFpEF phenotype. In diabetic HFpEF, comprehensive cardiac MRI provides incremental value in predicting prognosis. Particularly, MRI-FT measurement of GLS is an independent predictor of adverse outcome in diabetic HFpEF.CLINICAL RELEVANCE STATEMENT:Our findings suggested that MRI-derived variables, especially global longitudinal strain, played a crucial role in risk stratification and predicting worse prognosis in diabetic heart failure with preserved ejection fraction, which could assist in identifying high-risk patients and guiding therapeutic decision-making.KEY POINTS:• Limited data are available on the cardiac MRI features of diabetic heart failure with preserved ejection fraction, including myocardial deformation and tissue characterization, as well as their incremental prognostic value. • Diabetic heart failure with preserved ejection fraction patients was characterized by more impaired strains and myocardial fibrosis. Comprehensive MRI, including tissue characterization and global longitudinal strain, provided incremental value for risk prediction. • MRI served as a valuable tool for identifying high-risk patients and guiding clinical management in diabetic heart failure with preserved ejection fraction.

Granzyme B PET imaging inflammation and remodeling in myocardial infarction.

PURPOSE:This study aimed to evaluate whether granzyme B (GzmB)-targeted positron emission tomography (PET) imaging agent (68 Ga-grazytracer) can characterize cardiac inflammation and remodeling in myocardial infarction (MI).METHODS:Rats with MI were subjected to GzmB-targeted PET/CT on post-operative days 1, 3, 6, 14, and 28. Autoradiography, Masson staining, immunohistochemistry, and ELISA were performed to verify the inflammatory response and remodeling after MI in vitro. Rats were treated with GzmB inhibitor Z-IETD-FMK to improve cardiac remodeling. Cardiac function tests were performed by echocardiography at 6 weeks after MI.RESULTS:The highest uptake of 68 Ga-grazytracer was observed on day 3 after MI compared with the values obtained on the other days (0.294 ± 0.03% ID/g at 3 days vs. 0.122 ± 0.01% ID/g in the sham group, P < 0.001). Immunohistochemistry showed significantly high expression of GzmB and CD8, in line with the PET/CT imaging results. Autoradiography revealed 68 Ga-grazytracer accumulation in the infarcted myocardium. The 68 Ga-grazytracer uptake of treated rats was significantly reduced compared with that in the MI groups (0.184 ± 0.03%ID/g vs. 0.286 ± 0.03%ID/g; P < 0.001). Echocardiography showed that the left ventricular ejection fraction was lower in the MI groups than in the ischemia reperfusion group. GzmB inhibitor treatment was shown to be effective in improving cardiac function without significantly shortening infarct size.CONCLUSIONS:This study demonstrated the potential of 68 Ga-grazytracer imaging to delineate adverse inflammatory responses and pathological cardiac remodeling, which can help predict heart function. PET/CT imaging-guided therapy may reduce myocardial injury and improve heart function in MI.

Adenosine Triphosphate Stress Myocardial Strain in Ischemic Heart Disease: An Animal Study with Histological Validation.

RATIONALE AND OBJECTIVES:It is still challenging for cardiac magnetic resonance (CMR) to detect ischemic heart disease (IHD) without the use of gadolinium contrast. We aimed to evaluate the potential value of adenosine triphosphate (ATP) stress myocardial strain derived from feature tracking (FT) as a novel method for detecting IHD in a swine model.MATERIALS AND METHODS:CMR cines, myocardial perfusion imaging at rest and during ATP stress, and late gadolinium enhancement were obtained in both control and IHD swine. Normal, remote, ischemic, and infarcted myocardium were analyzed. The diagnostic accuracy of myocardial strain for infarction and ischemia was assessed using coronary angiography and pathology as reference.RESULTS:Eleven IHD swine and five healthy control swine were enrolled in this study. Strain parameters, even at rest, were associated with myocardial ischemia and infarction(all p < 0.05). The area under receiver operating characteristic curve (AUC) values of all strain parameters for detecting infarcted myocardium exceeded 0.900 (all p < 0.05). The AUC values for detecting ischemic myocardium were as follows: 0.906 and 0.847 for stress and rest radial strain, 0.763 and 0.716 for stress and rest circumferential strain, 0.758 and 0.663 for stress and rest longitudinal strain (all p < 0.001). Heat maps demonstrated that all strain parameters showed mild to moderate correlations with the stress myocardial blood flow and myocardial perfusion reserve (all p < 0.05).CONCLUSION:CMR-FT-derived ATP stress myocardial strain shows promise as a noninvasive method for detecting myocardial ischemia and infarction in an IHD swine model, with rest strain parameters offering potential as a needle-free diagnostic option.

Incremental Diagnostic Value of Right Ventricular Strain Analysis in Arrhythmogenic Right Ventricular Cardiomyopathy.

BACKGROUND:Strain analysis is a sensitive method for the assessment of ventricular structural or functional alterations. The authors aimed to determine whether right ventricular (RV) strain parameters can discriminate patients with revised Task Force Criteria-diagnosed arrhythmogenic RV cardiomyopathy (ARVC) incremental to the existing cardiovascular magnetic resonance (CMR) criteria, thus improving the diagnostic yield of CMR in ARVC.METHODS AND RESULTS:A total of 74 patients with revised Task Force Criteria-diagnosed ARVC (37 borderline and 37 definite) and 37 controls were retrospectively enrolled for analysis. Using CMR feature tracking, RV global longitudinal (GLS), circumferential, and radial strain of all participants were evaluated. Compared with controls, the study patients demonstrated significantly impaired global biventricular strain in all 3 directions (all P<0.001). Receiver operating characteristic curve analysis indicated that RV GLS was the strongest discriminator among all RV strain parameters for the identification of patients with ARVC (area under the curve, 0.92). Using the Youden index, the authors determined RV GLS ≥-19.95% as the diagnostic criterion of ARVC. In patients diagnosed with borderline ARVC according to revised Task Force Criteria but with no or only minor CMR criteria, there were >50% presenting with impaired RV GLS. When both conventional criteria and RV GLS were considered together, this new diagnostic method demonstrated an overall diagnostic accuracy of 90%. The likelihood ratio test showed a significant incremental diagnostic value of RV GLS (P=0.02) over the existing CMR major criteria.CONCLUSIONS:The current study showed an improved diagnostic accuracy when both RV GLS and the existing CMR criteria were considered together, especially for patients with borderline diagnosis, suggesting the incremental value of strain analysis to the initial assessment of ARVC.

Developing and evaluating a chronic ischemic cardiomyopathy in swine model by rest and stress CMR.

A large animal model of chronic coronary artery disease (CAD) is crucial for the understanding the underlying pathophysiological processes of chronic CAD and consequences for cardiac structure and function. The goal of this study was to develop a chronic model of CAD in a swine model and to evaluate the changes of myocardial structure, myocardial motility, and myocardial viability during coronary stenosis. A total of 30 swine (including 24 experimental animals and 6 controls) were enrolled. The chronic ischemia model was constructed by using Ameroid constrictor in experimental group. The 24 experimental animals were further divided into 4 groups (6 animals in each group) and were sacrificed at 1, 2, 3 and 4 weeks after operation for pathological examination, respectively. Cardiac magnetic resonance (CMR) was performed preoperatively and weekly postoperatively until sacrificed both in experimental and control group. CMR cine images, rest/adenosine triphosphate (ATP) stress myocardial contrast perfusion and LGE were performed and analyzed. The rest wall thickening (WT) score was calculated from rest cine images. The MPRI (myocardial perfusion reserve index) and MPR (myocardial perfusion reserve) were calculated based on rest and stress perfusion images. Pathology staining including triphenyltetrazolium chloride, HE and picrosirus red staining were performed after swine were sacrificed and collagen volume fraction (CVF) was calculated. The time to formation of ischemic, hibernating, and infarcted myocardium was recorded. In experimental group, from 1w to 4w after surgery, the rest WT score decreased gradually from 35.2 ± 2.0%, 32.0 ± 2.9% to 30.5 ± 3.0% and finally 29.06 ± 1.78%, p < 0.001. Left ventricular ejection fraction was gradually impaired after modeling (58.9 ± 12.6%, 56.3 ± 10.1%, 55.3 ± 9.0%, 53.8 ± 9.9%, respectively). And the MPR and MPRI also decreased stepwise with extent of surgery time (MPRI dropped from 2.1 ± 0.4, 2.0 ± 0.2 to 1.8 ± 0.3 and finally 1.7 ± 0.1, p = 0.004; MPR dropped from 2.3 ± 0.4, 2.1 ± 0.2 to 1.9 ± 0.4 and finally 1.8 ± 0.1, p < 0.001). Stronger associations between MPR, MPRI and CVF were paralleled lower wall thickening scores in fibrosis-affected areas. The ischemic myocardium was first appeared in the first week after surgery (involving ten segments), hibernated myocardium was first appeared in the second week after surgery (involving seventeen segments). LGE was first appeared in eight swine in the third weeks after surgery (16 segments). At 4w after surgery, average 9.6 g scar tissue was found among 6 swine. At the same time, histological analysis established the presence of fibrosis and ongoing apoptosis in the infarcted area. In conclusion, our study provided valuable insights into the pathophysiological processes of chronic CAD and its consequences for cardiac structure and function in a large animal model through combining myocardial motion and stress perfusion.

Unravelling the intricacies of left ventricular haemodynamic forces: age and gender-specific normative values assessed by cardiac MRI in healthy adults.

AIMS:Haemodynamic forces (HDFs) provided a feasible method to early detect cardiac mechanical abnormalities by estimating the intraventricular pressure gradients. The novel advances in assessment of HDFs using routine cardiac magnetic resonance (CMR) cines shed new light on detection of preclinical dysfunction. However, definition of normal values for this new technique is the prerequisite for application in the clinic.METHODS AND RESULTS:A total of 218 healthy volunteers [38.1 years ± 11.1; 111 male (50.9%)] were recruited and underwent CMR examinations with a 3.0T scanner. Balanced steady state free precession breath hold cine images were acquired, and HDF assessments were performed based on strain analysis. The normal values of longitudinal and transversal HDF strength [root mean square (RMS)] and ratio of transversal to longitudinal HDF were all evaluated in overall population as well as in both genders and in age-specific groups. The longitudinal RMS values (%) of HDFs were significantly higher in women (P < 0.05). Moreover, the HDF amplitudes significantly decreased with ageing in entire heartbeat, systole, diastole, systolic/diastolic transition, and diastolic deceleration, while increased in atrial thrust. In multivariable linear regression analysis, age, heart rate, and global longitudinal strain emerged as independent predictors of the amplitudes of longitudinal HDFs in entire heartbeat and systole, while left ventricular end-diastole volume index was also independently associated with longitudinal HDFs in diastole and diastolic deceleration (P < 0.05 for all).CONCLUSION:Our study provided comprehensive normal values of HDF assessments using CMR as well as presented with specific age and sex stratification. HDF analyses can be performed with excellent intra- and inter-observer reproducibility.

Ventricular-atrial coupling in subjects with normal, preserved, and reduced left ventricular ejection fraction: insights from cardiac magnetic resonance imaging.

OBJECTIVES:To assess the correlation between LA and LV strain measurements in different clinical scenarios and evaluate to what extent LA deformation contributes to the prognosis of patients.METHODS:A total of 297 consecutive participants including 75 healthy individuals, 75 hypertrophic cardiomyopathy (HCM) patients, 74 idiopathic dilated cardiomyopathy (DCM), and 73 chronic myocardial infarction (MI) patients were retrospectively enrolled in this study. The associations of LA-LV coupling with clinical status were statistically analyzed by correlation, multiple linear regression, and logistic regression. Survival estimates were calculated by receiver operating characteristic analyses and Cox regression analyses.RESULTS:Overall, moderate correlations were found between LA and LV strain in every phase of the cardiac cycle (r: -0.598 to -0.580, all p < 0.001). The slope of the regression line of the individual strain-strain curve had a significant difference among 4 groups (-1.4 ± 0.3 in controls, -1.1 ± 0.6 in HCM, -1.8 ± 0.8 in idiopathic DCM, -2.4 ± 1.1 in chronic MI, all p < 0.05). During a median follow-up of 4.7 years, the total LA emptying fraction was independently associated with primary (hazard ratio: 0.968, 95% CI: 0.951-0.985) and secondary endpoints (hazard ratio: 0.957, 95% CI: 0.930-0.985) with an area under the curve (AUC) of 0.720 respectively, 0.806, which was significantly higher than the AUC of LV parameters.CONCLUSIONS:The coupled correlations between the left atria and ventricle in every phase and the individual strain-strain curve vary with etiology. LA deformation in late diastole provides prior and incremental information on cardiac dysfunction based on LV metrics. The total LA emptying fraction was an independent indicator for clinical outcome superior to that of LV typical predictors.CLINICAL RELEVANCE STATEMENT:Left ventricular-atrial coupling is not only valuable for comprehending the pathophysiological mechanisms of cardiovascular diseases caused by different etiologies but also holds significant importance for the prevention of adverse cardiovascular events and targeted treatment.KEY POINTS:• In HCM patients with preserved LVEF, LA deformation is a sensitive indicator for cardiac dysfunction prior to LV parameters with a reduced LA/LV strain ratio. • In patients with reduced LVEF, LV deformation impairment is more consequential than that of the LA with an increased LA/LV strain ratio. Furthermore, impaired LA active strain indicates potential atrial myopathy. • Among LA and LV parameters, the total LA emptying fraction is the best predictor for guiding clinical management and follow-up in patients with different statuses of LVEF.

Myocardial bridging in obstructive hypertrophic cardiomyopathy: a risk factor for myocardial fibrosis.

BACKGROUND:Myocardial bridging (MB) is common in patients with hypertrophic cardiomyopathy (HCM). There are sparse data on the impact of MB on myocardial fibrosis in HCM. This study was designed to evaluate the relationship between MB and myocardial fibrosis in patients with obstructive HCM.METHODS:In this cohort study, retrospective data were collected from a high-volume HCM center. Patients with obstructive HCM who underwent septal myectomy and preoperative cardiac magnetic resonance (CMR) were screened from 2011 to 2018.RESULTS:Finally, 492 patients were included in this study, with an average age of 45.7 years. Of these patients, 76 patients had MB. MB occurred mostly in the left anterior descending artery (73/76). The global extent of late gadolinium enhancement (LGE) was correlated with the degree of systolic compression (r = 0.33, p = 0.003). Multivariable linear regression analysis revealed that the degree of systolic compression was an independent risk factor for LGE (β = 0.292, p = 0.007). The LGE fraction of basal and mid anteroseptal segments in patients with severe MB (compression ratio ≥ 80%) was significantly greater than that in patients with mild to moderate MB (compression ratio < 80%). During a median follow-up of 28 (IQR: 15-52) months, 15 patients died. Kaplan-Meier analysis did not identify differences in all-cause death (log-rank p = 0.63) or cardiovascular death (log-rank p = 0.72) between patients undergoing MB-related surgery and those without MB.CONCLUSIONS:MB with severe systolic compression was significantly associated with a high extent of fibrosis in patients with obstructive HCM. Concomitant myotomy or coronary artery bypass grafting might provide excellent survival similar to that of patients without MB. Identification of patients with severe MB and providing comprehensive management might help improve the prognosis of patients with HCM.

Association between QRS voltages and amyloid burden in patients with cardiac amyloidosis.

Association between left atrial myopathy and sarcomere mutation in patients with hypertrophic cardiomyopathy: insights into left atrial strain by MRI feature tracking.

OBJECTIVES:Left atrial (LA) myopathy, characterized by LA enlargement and mechanical dysfunction, is associated with worse prognosis in hypertrophic cardiomyopathy (HCM) while the impact of sarcomere mutation on LA myopathy remains unclear. We aimed to assess the association between LA myopathy and sarcomere mutation and to explore the incremental utility of LA strain in mutation prediction.METHODS:A total of 105 consecutive HCM patients (mean age 47.8 ± 11.9 years, 71% male) who underwent HCM-related gene screening and cardiac MRI were retrospectively enrolled. LA volume, ejection fraction and strain indices in reservoir, conduit, and booster-pump phases were investigated respectively.RESULTS:Fifty mutation-positive patients showed higher LA maximal volume index (59.4 ± 28.2 vs 43.8 ± 18.1 mL/m2, p = 0.001), lower reservoir (21.3 ± 7.9 vs 26.2 ± 6.6%, p < 0.001), and booster-pump strain (12.1 ± 5.4 vs 17.1 ± 5.0%, p < 0.001) but similar conduit strain (9.2 ± 4.5 vs 9.1 ± 4.5%, p = 0.909) compared with mutation-negative patients. In multivariate logistic regression, LA booster-pump strain was associated with sarcomere mutation (odds ratio = 0.86, 95% confidence interval: 0.77-0.96, p = 0.010) independent of maximal wall thickness, late gadolinium enhancement, and LA volume. Furthermore, LA booster-pump strain showed incremental value for mutation prediction added to Mayo II score (AUC 0.798 vs 0.709, p = 0.024).CONCLUSIONS:In HCM, mutation-positive patients suffered worse LA enlargement and worse reservoir and booster-pump functions. LA booster-pump strain was a strong factor for sarcomere mutation prediction added to Mayo II score.CLINICAL RELEVANCE STATEMENT:The independent association between sarcomere mutation and left atrial mechanical dysfunction provide new insights into the pathogenesis of atrial myopathy and is helpful to understand the adverse prognosis regarding atrial fibrillation and stroke in mutation-positive patients.KEY POINTS:• In patients with hypertrophic cardiomyopathy, left atrial (LA) reservoir and booster-pump function, but not conduit function, were significantly impaired in mutation-positive patients compared with mutation-negative patients. • LA booster-pump strain measured by MRI-derived feature tracking is feasible to predict sarcomere mutation with high incremental value added to Mayo II score.

Long-term outcomes prediction in diabetic heart failure with preserved ejection fraction by cardiac MRI.

OBJECTIVES:We aimed to explore imaging features including tissue characterization and myocardial deformation in diabetic heart failure with preserved ejection fraction (HFpEF) patients by magnetic resonance imaging (MRI) and investigate its prognostic value for adverse outcomes.MATERIALS AND METHODS:Patients with HFpEF who underwent cardiac MRI between January 2010 and December 2016 were enrolled. Feature-tracking (FT) analysis and myocardial fibrosis were assessed by cardiac MRI. Cox proportional regression analysis was performed to determine the association between MRI variables and primary outcomes. Primary outcomes were all-cause death or heart failure hospitalization during the follow-up period.RESULTS:Of the 335 enrolled patients with HFpEF, 191 had diabetes mellitus (DM) (mean age: 58.7 years ± 10.8; 137 men). During a median follow-up of 10.2 years, 91 diabetic HFpEF and 56 non-diabetic HFpEF patients experienced primary outcomes. DM was a significant predictor of worse prognosis in HFpEF. In diabetic HFpEF, the addition of conventional imaging variables (left ventricular ejection fraction, left atrial volume index, extent of late gadolinium enhancement (LGE)) and global longitudinal strain (GLS) resulted in a significant increase in the area under the receiver operating characteristic curve (from 0.693 to 0.760, p < 0.05). After adjustment for multiple clinical and imaging variables, each 1% worsening in GLS was associated with a 9.8% increased risk of adverse events (p = 0.004).CONCLUSIONS:Diabetic HFpEF is characterized by more severely impaired strains and myocardial fibrosis, which is identified as a high-risk HFpEF phenotype. In diabetic HFpEF, comprehensive cardiac MRI provides incremental value in predicting prognosis. Particularly, MRI-FT measurement of GLS is an independent predictor of adverse outcome in diabetic HFpEF.CLINICAL RELEVANCE STATEMENT:Our findings suggested that MRI-derived variables, especially global longitudinal strain, played a crucial role in risk stratification and predicting worse prognosis in diabetic heart failure with preserved ejection fraction, which could assist in identifying high-risk patients and guiding therapeutic decision-making.KEY POINTS:• Limited data are available on the cardiac MRI features of diabetic heart failure with preserved ejection fraction, including myocardial deformation and tissue characterization, as well as their incremental prognostic value. • Diabetic heart failure with preserved ejection fraction patients was characterized by more impaired strains and myocardial fibrosis. Comprehensive MRI, including tissue characterization and global longitudinal strain, provided incremental value for risk prediction. • MRI served as a valuable tool for identifying high-risk patients and guiding clinical management in diabetic heart failure with preserved ejection fraction.

Granzyme B PET imaging inflammation and remodeling in myocardial infarction.

PURPOSE:This study aimed to evaluate whether granzyme B (GzmB)-targeted positron emission tomography (PET) imaging agent (68 Ga-grazytracer) can characterize cardiac inflammation and remodeling in myocardial infarction (MI).METHODS:Rats with MI were subjected to GzmB-targeted PET/CT on post-operative days 1, 3, 6, 14, and 28. Autoradiography, Masson staining, immunohistochemistry, and ELISA were performed to verify the inflammatory response and remodeling after MI in vitro. Rats were treated with GzmB inhibitor Z-IETD-FMK to improve cardiac remodeling. Cardiac function tests were performed by echocardiography at 6 weeks after MI.RESULTS:The highest uptake of 68 Ga-grazytracer was observed on day 3 after MI compared with the values obtained on the other days (0.294 ± 0.03% ID/g at 3 days vs. 0.122 ± 0.01% ID/g in the sham group, P < 0.001). Immunohistochemistry showed significantly high expression of GzmB and CD8, in line with the PET/CT imaging results. Autoradiography revealed 68 Ga-grazytracer accumulation in the infarcted myocardium. The 68 Ga-grazytracer uptake of treated rats was significantly reduced compared with that in the MI groups (0.184 ± 0.03%ID/g vs. 0.286 ± 0.03%ID/g; P < 0.001). Echocardiography showed that the left ventricular ejection fraction was lower in the MI groups than in the ischemia reperfusion group. GzmB inhibitor treatment was shown to be effective in improving cardiac function without significantly shortening infarct size.CONCLUSIONS:This study demonstrated the potential of 68 Ga-grazytracer imaging to delineate adverse inflammatory responses and pathological cardiac remodeling, which can help predict heart function. PET/CT imaging-guided therapy may reduce myocardial injury and improve heart function in MI.

Adenosine Triphosphate Stress Myocardial Strain in Ischemic Heart Disease: An Animal Study with Histological Validation.

RATIONALE AND OBJECTIVES:It is still challenging for cardiac magnetic resonance (CMR) to detect ischemic heart disease (IHD) without the use of gadolinium contrast. We aimed to evaluate the potential value of adenosine triphosphate (ATP) stress myocardial strain derived from feature tracking (FT) as a novel method for detecting IHD in a swine model.MATERIALS AND METHODS:CMR cines, myocardial perfusion imaging at rest and during ATP stress, and late gadolinium enhancement were obtained in both control and IHD swine. Normal, remote, ischemic, and infarcted myocardium were analyzed. The diagnostic accuracy of myocardial strain for infarction and ischemia was assessed using coronary angiography and pathology as reference.RESULTS:Eleven IHD swine and five healthy control swine were enrolled in this study. Strain parameters, even at rest, were associated with myocardial ischemia and infarction(all p < 0.05). The area under receiver operating characteristic curve (AUC) values of all strain parameters for detecting infarcted myocardium exceeded 0.900 (all p < 0.05). The AUC values for detecting ischemic myocardium were as follows: 0.906 and 0.847 for stress and rest radial strain, 0.763 and 0.716 for stress and rest circumferential strain, 0.758 and 0.663 for stress and rest longitudinal strain (all p < 0.001). Heat maps demonstrated that all strain parameters showed mild to moderate correlations with the stress myocardial blood flow and myocardial perfusion reserve (all p < 0.05).CONCLUSION:CMR-FT-derived ATP stress myocardial strain shows promise as a noninvasive method for detecting myocardial ischemia and infarction in an IHD swine model, with rest strain parameters offering potential as a needle-free diagnostic option.

Incremental Diagnostic Value of Right Ventricular Strain Analysis in Arrhythmogenic Right Ventricular Cardiomyopathy.

BACKGROUND:Strain analysis is a sensitive method for the assessment of ventricular structural or functional alterations. The authors aimed to determine whether right ventricular (RV) strain parameters can discriminate patients with revised Task Force Criteria-diagnosed arrhythmogenic RV cardiomyopathy (ARVC) incremental to the existing cardiovascular magnetic resonance (CMR) criteria, thus improving the diagnostic yield of CMR in ARVC.METHODS AND RESULTS:A total of 74 patients with revised Task Force Criteria-diagnosed ARVC (37 borderline and 37 definite) and 37 controls were retrospectively enrolled for analysis. Using CMR feature tracking, RV global longitudinal (GLS), circumferential, and radial strain of all participants were evaluated. Compared with controls, the study patients demonstrated significantly impaired global biventricular strain in all 3 directions (all P<0.001). Receiver operating characteristic curve analysis indicated that RV GLS was the strongest discriminator among all RV strain parameters for the identification of patients with ARVC (area under the curve, 0.92). Using the Youden index, the authors determined RV GLS ≥-19.95% as the diagnostic criterion of ARVC. In patients diagnosed with borderline ARVC according to revised Task Force Criteria but with no or only minor CMR criteria, there were >50% presenting with impaired RV GLS. When both conventional criteria and RV GLS were considered together, this new diagnostic method demonstrated an overall diagnostic accuracy of 90%. The likelihood ratio test showed a significant incremental diagnostic value of RV GLS (P=0.02) over the existing CMR major criteria.CONCLUSIONS:The current study showed an improved diagnostic accuracy when both RV GLS and the existing CMR criteria were considered together, especially for patients with borderline diagnosis, suggesting the incremental value of strain analysis to the initial assessment of ARVC.

Developing and evaluating a chronic ischemic cardiomyopathy in swine model by rest and stress CMR.

A large animal model of chronic coronary artery disease (CAD) is crucial for the understanding the underlying pathophysiological processes of chronic CAD and consequences for cardiac structure and function. The goal of this study was to develop a chronic model of CAD in a swine model and to evaluate the changes of myocardial structure, myocardial motility, and myocardial viability during coronary stenosis. A total of 30 swine (including 24 experimental animals and 6 controls) were enrolled. The chronic ischemia model was constructed by using Ameroid constrictor in experimental group. The 24 experimental animals were further divided into 4 groups (6 animals in each group) and were sacrificed at 1, 2, 3 and 4 weeks after operation for pathological examination, respectively. Cardiac magnetic resonance (CMR) was performed preoperatively and weekly postoperatively until sacrificed both in experimental and control group. CMR cine images, rest/adenosine triphosphate (ATP) stress myocardial contrast perfusion and LGE were performed and analyzed. The rest wall thickening (WT) score was calculated from rest cine images. The MPRI (myocardial perfusion reserve index) and MPR (myocardial perfusion reserve) were calculated based on rest and stress perfusion images. Pathology staining including triphenyltetrazolium chloride, HE and picrosirus red staining were performed after swine were sacrificed and collagen volume fraction (CVF) was calculated. The time to formation of ischemic, hibernating, and infarcted myocardium was recorded. In experimental group, from 1w to 4w after surgery, the rest WT score decreased gradually from 35.2 ± 2.0%, 32.0 ± 2.9% to 30.5 ± 3.0% and finally 29.06 ± 1.78%, p < 0.001. Left ventricular ejection fraction was gradually impaired after modeling (58.9 ± 12.6%, 56.3 ± 10.1%, 55.3 ± 9.0%, 53.8 ± 9.9%, respectively). And the MPR and MPRI also decreased stepwise with extent of surgery time (MPRI dropped from 2.1 ± 0.4, 2.0 ± 0.2 to 1.8 ± 0.3 and finally 1.7 ± 0.1, p = 0.004; MPR dropped from 2.3 ± 0.4, 2.1 ± 0.2 to 1.9 ± 0.4 and finally 1.8 ± 0.1, p < 0.001). Stronger associations between MPR, MPRI and CVF were paralleled lower wall thickening scores in fibrosis-affected areas. The ischemic myocardium was first appeared in the first week after surgery (involving ten segments), hibernated myocardium was first appeared in the second week after surgery (involving seventeen segments). LGE was first appeared in eight swine in the third weeks after surgery (16 segments). At 4w after surgery, average 9.6 g scar tissue was found among 6 swine. At the same time, histological analysis established the presence of fibrosis and ongoing apoptosis in the infarcted area. In conclusion, our study provided valuable insights into the pathophysiological processes of chronic CAD and its consequences for cardiac structure and function in a large animal model through combining myocardial motion and stress perfusion.

Unravelling the intricacies of left ventricular haemodynamic forces: age and gender-specific normative values assessed by cardiac MRI in healthy adults.

AIMS:Haemodynamic forces (HDFs) provided a feasible method to early detect cardiac mechanical abnormalities by estimating the intraventricular pressure gradients. The novel advances in assessment of HDFs using routine cardiac magnetic resonance (CMR) cines shed new light on detection of preclinical dysfunction. However, definition of normal values for this new technique is the prerequisite for application in the clinic.METHODS AND RESULTS:A total of 218 healthy volunteers [38.1 years ± 11.1; 111 male (50.9%)] were recruited and underwent CMR examinations with a 3.0T scanner. Balanced steady state free precession breath hold cine images were acquired, and HDF assessments were performed based on strain analysis. The normal values of longitudinal and transversal HDF strength [root mean square (RMS)] and ratio of transversal to longitudinal HDF were all evaluated in overall population as well as in both genders and in age-specific groups. The longitudinal RMS values (%) of HDFs were significantly higher in women (P < 0.05). Moreover, the HDF amplitudes significantly decreased with ageing in entire heartbeat, systole, diastole, systolic/diastolic transition, and diastolic deceleration, while increased in atrial thrust. In multivariable linear regression analysis, age, heart rate, and global longitudinal strain emerged as independent predictors of the amplitudes of longitudinal HDFs in entire heartbeat and systole, while left ventricular end-diastole volume index was also independently associated with longitudinal HDFs in diastole and diastolic deceleration (P < 0.05 for all).CONCLUSION:Our study provided comprehensive normal values of HDF assessments using CMR as well as presented with specific age and sex stratification. HDF analyses can be performed with excellent intra- and inter-observer reproducibility.

Ventricular-atrial coupling in subjects with normal, preserved, and reduced left ventricular ejection fraction: insights from cardiac magnetic resonance imaging.

OBJECTIVES:To assess the correlation between LA and LV strain measurements in different clinical scenarios and evaluate to what extent LA deformation contributes to the prognosis of patients.METHODS:A total of 297 consecutive participants including 75 healthy individuals, 75 hypertrophic cardiomyopathy (HCM) patients, 74 idiopathic dilated cardiomyopathy (DCM), and 73 chronic myocardial infarction (MI) patients were retrospectively enrolled in this study. The associations of LA-LV coupling with clinical status were statistically analyzed by correlation, multiple linear regression, and logistic regression. Survival estimates were calculated by receiver operating characteristic analyses and Cox regression analyses.RESULTS:Overall, moderate correlations were found between LA and LV strain in every phase of the cardiac cycle (r: -0.598 to -0.580, all p < 0.001). The slope of the regression line of the individual strain-strain curve had a significant difference among 4 groups (-1.4 ± 0.3 in controls, -1.1 ± 0.6 in HCM, -1.8 ± 0.8 in idiopathic DCM, -2.4 ± 1.1 in chronic MI, all p < 0.05). During a median follow-up of 4.7 years, the total LA emptying fraction was independently associated with primary (hazard ratio: 0.968, 95% CI: 0.951-0.985) and secondary endpoints (hazard ratio: 0.957, 95% CI: 0.930-0.985) with an area under the curve (AUC) of 0.720 respectively, 0.806, which was significantly higher than the AUC of LV parameters.CONCLUSIONS:The coupled correlations between the left atria and ventricle in every phase and the individual strain-strain curve vary with etiology. LA deformation in late diastole provides prior and incremental information on cardiac dysfunction based on LV metrics. The total LA emptying fraction was an independent indicator for clinical outcome superior to that of LV typical predictors.CLINICAL RELEVANCE STATEMENT:Left ventricular-atrial coupling is not only valuable for comprehending the pathophysiological mechanisms of cardiovascular diseases caused by different etiologies but also holds significant importance for the prevention of adverse cardiovascular events and targeted treatment.KEY POINTS:• In HCM patients with preserved LVEF, LA deformation is a sensitive indicator for cardiac dysfunction prior to LV parameters with a reduced LA/LV strain ratio. • In patients with reduced LVEF, LV deformation impairment is more consequential than that of the LA with an increased LA/LV strain ratio. Furthermore, impaired LA active strain indicates potential atrial myopathy. • Among LA and LV parameters, the total LA emptying fraction is the best predictor for guiding clinical management and follow-up in patients with different statuses of LVEF.