Mitral Annular Tissue Velocity Predicts Survival in Patients With Primary Mitral Regurgitation.

BACKGROUND AND OBJECTIVES: Early diastolic mitral annular tissue (e') velocity is a commonly used marker of left ventricular (LV) diastolic function. This study aimed to investigate the prognostic implications of e' velocity in patients with mitral regurgitation (MR). METHODS: This retrospective cohort study included 1,536 consecutive patients aged <65 years with moderate or severe chronic primary MR diagnosed between 2009 and 2018. The primary and secondary outcomes were all-cause and cardiovascular mortality, respectively. According to the current guidelines, the cut-off value of e' velocity was defined as 7 cm/s. RESULTS: A total of 404 individuals were enrolled (median age, 51.0 years; 64.1% male; 47.8% severe MR). During a median 6.0-year follow-up, there were 40 all-cause mortality and 16 cardiovascular deaths. Multivariate analysis revealed a significant association between e' velocity and all-cause death (adjusted hazard ratio [aHR], 0.770; 95% confidence interval [CI], 0.634-0.935; p=0.008) and cardiovascular death (aHR, 0.690; 95% CI, 0.477-0.998; p=0.049). Abnormal e' velocity (≤7 cm/s) independently predicted all-cause death (aHR, 2.467; 95% CI, 1.170-5.200; p=0.018) and cardiovascular death (aHR, 5.021; 95% CI, 1.189-21.211; p=0.028), regardless of symptoms, LV dimension and ejection fraction. Subgroup analysis according to sex, MR severity, mitral valve replacement/repair, and symptoms, showed no significant interactions. Including e' velocity in the 10-year risk score improved reclassification for mortality (net reclassification improvement [NRI], 0.154; 95% CI, 0.308-0.910; p<0.001) and cardiovascular death (NRI, 1.018; 95% CI, 0.680-1.356; p<0.001). CONCLUSIONS: In patients aged <65 years with primary MR, e' velocity served as an independent predictor of all-cause and cardiovascular deaths.

Cardiac sarcoidosis.

The diagnostic yield of endomyocardial biopsy in cardiac sarcoidosis (CS) is quite low because of the patchy involvement, and for the diagnosis of CS, existing guidelines required histological confirmation. Therefore, especially for isolated CS, diagnosis consistent with the guidelines cannot be made in a large number of patients. With recent developments in imaging modalities such as cardiac magnetic resonance and 18-fluorodeoxyglucose positron emission tomography, diagnosing CS has become easier and diagnostic criteria for CS not compulsorily requiring histological confirmation have been suggested. Despite significant advances in diagnostic tools, large-scale studies that can guide treatment plans are still lacking, and treatment has relied on the experience accumulated over the past years and the consensus of experts. However, opinions vary, depending on the situation, which is quite puzzling for the physician treating CS. Moreover, with the advent of new immunosuppressant agents, these new drugs have been applied under the assumption that the effect of immunosuppression is not much different from that of other well-known autoimmune diseases that require immunosuppression. However, we should wait to see the beneficial effects of these new immunosuppressants before we attempt to apply these agents in our clinical practice. This review summarises the widely used diagnostic criteria, current diagnostic modalities and recommended treatments for sarcoidosis. We have added our opinions on selecting or modifying diagnostic and treatment plans from the diverse current recommendations.

Network Analysis of Cardiac Remodeling by Primary Mitral Regurgitation Emphasizes the Role of Diastolic Function.

BACKGROUND: Topological data analysis (TDA) can generate patient-patient similarity networks by analyzing large, complex data and derive new insights that may not be possible with standard statistics. OBJECTIVES: The purpose of this paper was to discover novel phenotypes of chronic primary mitral regurgitation (MR) patients and to analyze their clinical implications using network analysis of echocardiographic data. METHODS: Patients with chronic moderate to severe primary MR were prospectively enrolled from 11 Asian tertiary hospitals (n = 850; mean age 56.9 ± 14.2 years, 57.9% men). We performed TDA to generate network models using 14 demographic and echocardiographic variables. The patients were grouped by phenotypes in the network, and the prognosis was compared by groups. RESULTS: The network model by TDA revealed 3 distinct phenogroups. Group A was the youngest with fewer comorbidities but increased left ventricular (LV) end-systolic volume, representing compensatory LV dilation commonly seen in chronic primary MR. Group B was the oldest with high blood pressure and a predominant diastolic dysfunction but relatively preserved LV size, an unnoticed phenotype in chronic primary MR. Group C showed advanced LV remodeling with impaired systolic, diastolic function, and LV dilation, indicating advanced chronic primary MR. During follow-up (median 3.5 years), 60 patients received surgery for symptomatic MR or died of cardiovascular causes. Kaplan-Meier curves demonstrated that although group C had the worst clinical outcome (P < 0.001), group B, characterized by diastolic dysfunction, had an event-free survival comparable to group A despite preserved LV chamber size. The grouping information by the network model was an independent predictor for the composite of MR surgery or cardiovascular death (adjusted HR: 1.918; 95% CI: 1.257-2.927; P = 0.003). CONCLUSIONS: The patient-patient similarity network by TDA visualized diverse remodeling patterns in chronic primary MR and revealed distinct phenotypes not emphasized currently. Importantly, diastolic dysfunction deserves equal attention when understanding the clinical presentation of chronic primary MR.

Independent Prognostic Utility of 11C-Pittsburgh Compound B PET in Patients with Light-Chain Cardiac Amyloidosis.

11C-Pittsburgh compound B (PiB) PET/CT visualizes the amount of myocardial amyloid deposit and can be used to prognosticate patients with amyloid light-chain (AL) cardiac amyloidosis (CA). However, whether 11C-PiB PET/CT has any independent additional prognostic value beyond the commonly used biomarkers remains unknown. Methods: This prospective study was on a cohort of 58 consecutive patients with AL CA who underwent 11C-PiB PET/CT. The patients were stratified into 2 groups on the basis of a visual assessment of whether there was myocardial 11C-PiB uptake on PET/CT. The primary endpoint was 1-y overall mortality. The independent prognostic utility of 11C-PiB PET/CT was analyzed using net reclassification improvement and integrated discrimination improvement. Results: Among the 58 patients enrolled, 35 were positive for myocardial 11C-PiB uptake on PET/CT. Patients with myocardial 11C-PiB PET uptake had a worse 1-y overall survival rate than those without (81.8% vs. 45.5%, P = 0.003 by log-rank test). In the multivariate analysis, positivity for myocardial 11C-PiB uptake on PET/CT was an independent predictor of 1-y mortality (adjusted hazard ratio, 3.382; 95% CI, 1.011-11.316; P = 0.048). In analysis of 3 subgroups of patients-those with a troponin I level of at least 0.1 ng/mL, those with an N-terminal pro-B-type natriuretic peptide (NT-proBNP) level of at least 1,800 pg/mL, and those with a difference of at least 180 mg/L between free light chains (the 3 commonly used biomarkers and their thresholds for staging in AL amyloidosis)-Kaplan-Meier curves showed for all 3 subgroups that patients positive for myocardial 11C-PiB uptake on PET/CT had a worse prognosis than those who were negative. Additionally, when the results of 11C-PiB PET/CT were added to these 3 biomarkers, the performance of 1-y mortality prediction significantly improved by net reclassification improvement (troponin I, 0.861; NT-proBNP, 0.914; difference between free light chains, 0.987) and by integrated discrimination improvement (0.200, 0.156, and 0.108, respectively). Conclusion:11C-PiB PET/CT is a strong independent predictor of 1-y overall mortality and provides incremental prognostic benefits beyond the 3 commonly used biomarkers of AL amyloidosis staging. Considering the recent development of numerous amyloid-targeting molecular imaging agents, further investigations are warranted on whether PET/CT should be included in risk stratification for patients with AL CA.

Prognostic implications of left ventricular mass-geometry in patients with no or nonobstructive coronary artery disease.

BACKGROUND: Coronary computed tomography angiography (CCTA) is widely used as a first-line noninvasive modality that frequently exhibits no or nonobstructive coronary artery disease (CAD) in clinical practice, along with abnormal left ventricular (LV) geometry on echocardiography. However, the combined prognostic value of these findings has not been well elucidated. Therefore, we aimed to evaluate the prognostic implications of abnormal LV geometry in individuals with no or nonobstructive CAD. METHODS: A total of 5806 subjects with no CAD or nonobstructive CAD (luminal narrowing < 50%) on CCTA were included in the study. The major exclusion criteria were structural heart disease and a history of myocardial infarction or coronary revascularization. Abnormal LV geometry on echocardiography was defined as LV mass index > 95 g/m2 in women and > 115 g/m2 in men, and/or relative wall thickness > 0.42. The primary outcome was all-cause mortality. RESULTS: A total of 5803 subjects without significant obstructive CAD (age, 56.6 ± 8.87 years; men, 3884 [66.9%]). Of them, 4045 (69.7%) subjects had normal LV geometry and 1758 (30.3%) had abnormal LV geometry respectively. During a mean follow-up of 6.2 ± 1.48 years, 84 (1.44%) subjects died in the study population. Of these, 56 subjects were from the normal LV geometry group (1.24%) and 28 were from the abnormal LV geometry group (2.32%). Subjects with abnormal LV geometry had significantly worse survival rates (log-rank, p < 0.001). After adjustment for confounding factors, abnormal LV geometry was an independent predictor of all-cause mortality (adjusted hazard ratio, 1.64; 95% confidence interval, 1.04-2.58; p = 0.034). Moreover, abnormal LV geometry was significantly worse in survival when classified as those with no CAD (log-rank, p = 0.024) and nonobstructive CAD (Log-rank, p < 0.001). CONCLUSIONS: Abnormal LV geometry portends a worse prognosis in subjects with no or nonobstructive CAD. These findings suggest that LV geometry assessment can help improve the stratification of individuals with these CCTA findings.

Time trajectory of cardiac function and its relation with survival in patients with light-chain cardiac amyloidosis.

AIMS: We aimed to analyse the time-serial change of cardiac function in light-chain (AL) cardiac amyloidosis patients undergoing active chemotherapy and its relationship with patient outcome. METHODS AND RESULTS: Seventy-two patients with AL cardiac amyloidosis undergoing active chemotherapy who had two or more echocardiographic examinations were identified from a prospective observational cohort (n = 34) and a retrospective cohort (n = 38). Echocardiographic parameters were obtained immediately prior to 1-3, 3-6, 6-12, and 12-24 months after the first chemotherapy. Study endpoint was a composite of death or heart transplantation (HT). During a median of 32 months (interquartile range 8-51) follow-up, 33 patients (45.8%) died and 4 patients (5.6%) underwent HT. Echocardiograms immediately prior to the first chemotherapy did not show differences between the patients with adverse events vs. those without. Significant increase in mitral E/e' ratio and decline in left ventricular global longitudinal strain (LV-GLS) was observed, starting at 3-6 months after the first chemotherapy only in those who experienced adverse events on follow-up, which was also evident in those who responded to chemotherapy. Multivariate analysis demonstrated that B-natriuretic peptide >500 pg/mL and troponin I >0.15 ng/dL at initial diagnosis, hospitalization for heart failure, E/e' >15, and LV-GLS <10% during follow-up were independent predictors of outcome. CONCLUSIONS: In AL cardiac amyloidosis patients undergoing active chemotherapy, the deterioration of LV function may occur, starting even at 3-6 months after the first chemotherapy. Serial echocardiography may help identify those who experience a clinical event in the near future despite active chemotherapy.

Progression of ascending aortopathy may not occur after transcatheter aortic valve replacement in severe bicuspid aortic stenosis.

BACKGROUND/AIMS: We evaluated changes in the ascending aorta dimension post-transcatheter aortic valve replacement (TAVR) in bicuspid aortic valve (BiAV) and tricuspid aortic valve (TAV) patients. METHODS: Patients with severe aortic stenosis undergoing TAVR at Seoul National University Hospital were consecutively recruited. Patients with less than 12 months' follow-up and/or with an ascending aorta size larger than 50 mm were excluded. The ascending aorta size was measured on a parasternal long axis view using transthoracic echocardiography. RESULTS: Among the 67 patients who were included (age: 76.5 ± 6.5 years; male: 52.2%; AV area: 0.67 ± 0.15 cm2), 19 (28.4%) had BiAV; 48 (71.6%) had TAV. The median (interquartile ranges) follow-up duration was 398 days (361 to 451). BiAV patients were younger (73.2 ± 7.2 vs. 77.8 ± 5.8, p = 0.008), and had lower incidences of chronic renal disease (5.3% vs. 35.4%, p = 0.014) and history of coronary intervention (15.8% vs. 50.0%, p = 0.013), than TAV patients. On pre-procedural echocardiography, the ascending aorta dimensions in BiAV patients were larger than those in TAV patients (40.5 ± 3.8 mm vs. 35.9 ± 4.2 mm, p < 0.005). The ascending aorta dimension changed minimally during follow-up; post-TAVR, the ascending aorta's growth rate was -0.11 ± 1.9 and 0.26 ± 1.8 mm/yr in patients with BiAV and TAV, respectively (p = 0.50). Progression of the ascending aorta's dimension postTAVR was not clinically significant in BiAV patients. CONCLUSION: The concern about the progression of aortopathy in BiAV patients post-TAVR may not be a clinical issue. This should be confirmed in studies with a larger population and with a longer follow-up duration.

Discrepancy of Aortic Valve Area Measurements by Doppler vs. Biplane Stroke Volume Measurements and Utility of Combining the Different Areas in Aortic Valve Stenosis　- The Asian Valve Registry.

BACKGROUND: The aortic valve area index (AVAI) in aortic stenosis (AS) is measured by echocardiography with a continuity equation using the stroke volume index by Doppler (SVIDoppler) or biplane Simpson (SVIBiplane) method. AVAIDopplerand AVAIBiplaneoften show discrepancy due to differences between SVIDopplerand SVIBiplane. The degree of discrepancy and utility of combined AVAIs have not been investigated in a large population of AS patients, and the characteristics of subjects with larger discrepancies are unknown.Methods and Results:We studied 820 patients with significant AS (AVADoppler<1.5 cm2) enrolled in the Asian Valve Registry, a prospective multicenter registry at 12 Asian centers. All-cause death and aortic valve replacement were defined as events. SVIDopplerwas significantly larger than SVIBiplane(49±11 vs. 39±11 mL/m2, P<0.01) and AVAIDopplerwas larger than AVAIBiplane(0.51±0.15 vs. 0.41±0.14 cm2/m2, P<0.01). An increase in (AVAIDoppler- AVAIBiplane) correlated with shorter height, lower weight, older age, smaller left ventricular (LV) diameter and increased velocity of ejection flow at the LV outflow tract. Severe AS by AVAIDoppleror AVAIBiplaneenabled prediction of events, and combining these AVAIs improved the predictive value of each. CONCLUSIONS: Discrepancy in AVAI by Doppler vs. biplane method was significantly more pronounced with increased LV outflow tract flow velocity, shorter height, lower weight, older age and smaller LV cavity dimensions. Combining the AVAIs enabled mutual and incremental value in predicting events.

Diffuse Myocardial Fibrosis and Diastolic Function in Aortic Stenosis.

OBJECTIVES: The aim of this study was to investigate the relationship between extracellular volume fraction (ECV), a noninvasive parameter that quantifies the degree of diffuse myocardial fibrosis on cardiac magnetic resonance (CMR), and left ventricular diastolic dysfunction (LVDD) in patients with aortic stenosis (AS). BACKGROUND: Myocardial fibrosis on invasive myocardial biopsy is associated with LVDD. However, there is a paucity of data on the association between noninvasively quantified diffuse myocardial fibrosis and the degree of LVDD and how these are related to symptoms and long-term prognosis in patients with AS. METHODS: Patients with moderate or severe AS (n = 191; mean age 68.4 years) and 30 control subjects without cardiovascular risk factors underwent CMR. LVDD grade was evaluated using echocardiography according to the 2016 American Society of Echocardiography/European Association of Cardiovascular Imaging guidelines. Clinical outcomes were defined as a composite of all-cause mortality or hospitalization for heart failure aggravation. RESULTS: Patients in higher ECV quintiles had a significantly higher prevalence of LVDD. Higher ECV was particularly associated with decreased myocardial relaxation (septal e' <7 cm/s) and increased LV filling pressure (E/e' ratio ≥15). Although both impaired diastolic function and higher ECV were significantly associated with a worse degree of dyspnea, patients with higher ECV showed greater dyspnea within the same grade of LVDD. During a median follow-up period of 5.6 years, 37 clinical events occurred. Increased ECV, as well as lower septal e' and higher E/septal e' ratio, were independent predictors of clinical events, irrespective of age, AS severity, aortic valve replacement, and left ventricular (LV) ejection fraction. ECV provided incremental prognostic value on top of clinical factors and LV systolic and diastolic function. CONCLUSIONS: Diffuse myocardial fibrosis, assessed using ECV on CMR, was associated with LVDD in patients with AS, but both ECV and LV diastolic function parameters provided a complementary explanation for dyspnea and clinical outcomes. Concomitant assessment of both LVDD and diffuse myocardial fibrosis may further identify patients with AS with greater symptoms and worse prognosis.

Early Surgery versus Watchful Waiting in Patients with Moderate Aortic Stenosis and Left Ventricular Systolic Dysfunction.

BACKGROUND AND OBJECTIVES: Severe aortic stenosis (AS) with left ventricular systolic dysfunction (LVSD) is a class I indication for aortic valve replacement (AVR) but this recommendation is not well established in those at the stage of moderate AS. We investigate the clinical impact of AVR among patients with moderate AS and LVSD. METHODS: From 2001 to 2017, we consecutively identified patients with moderate AS and LVSD, defined as aortic valve area 1.0-1.5 cm² and left ventricular ejection fraction <50%. The primary outcome was all-cause death. The outcomes were compared between those who underwent early surgical AVR (within 2 years of index echocardiography) at the stage of moderate AS versus those who were followed medically without AVR at the outpatient clinic. RESULTS: Among 255 patients (70.1±11.3 years, male 62%), 37 patients received early AVR. The early AVR group was younger than the medical observation group (63.1±7.9 vs. 71.3±11.4) with a lower prevalence of hypertension and chronic kidney disease. During a median 1.8-year follow up, 121 patients (47.5%) died, and the early AVR group showed a significantly lower all-cause death rate than the medical observation group (5.03PY vs. 18.80PY, p<0.001). After multivariable Cox-proportional hazard regression adjusting for age, sex, comorbidities, and laboratory data, early AVR at the stage of moderate AS significantly reduced the risk of death (hazard ratio, 0.43; 95% confidence interval 0.20-0.91; p=0.028). CONCLUSIONS: In patients with moderate AS and LVSD, AVR reduces the risk of all-cause death. A prospective randomized trial is warranted to confirm our findings.

Unsupervised Cluster Analysis of Patients With Aortic Stenosis Reveals Distinct Population With Different Phenotypes and Outcomes.

BACKGROUND: There is a lack of studies investigating the heterogeneity of patients with aortic stenosis (AS). We explored whether cluster analysis identifies distinct subgroups with different prognostic significances in AS. METHODS: Newly diagnosed patients with moderate or severe AS were prospectively enrolled between 2013 and 2016 (n=398, mean 71 years, 55% male). Among demographics, laboratory, and echocardiography parameters (n=32), 11 variables were selected through dimension reduction and used for unsupervised clustering. Phenotypes and causes of mortality were compared between the clusters. RESULTS: Three clusters with markedly different features were identified. Cluster 1 (n=60) was predominantly associated with cardiac dysfunction, cluster 2 (n=86) consisted of elderly with comorbidities, especially end-stage renal disease, whereas cluster 3 (n=252) demonstrated neither cardiac dysfunction nor comorbidities. Although AS severity did not differ, there was a significant difference in adverse outcomes between the clusters during a median 2.4 years follow-up (mortality rate, 13.3% versus 19.8% versus 6.0% for cluster 1, 2, and 3, P<0.001). Particularly, compared with cluster 3, cluster 1 was associated with only cardiac mortality (adjusted hazard ratio, 7.37 [95% CI, 2.00-27.13]; P=0.003), whereas cluster 2 was associated with higher noncardiac mortality (adjusted hazard ratio, 3.35 [95% CI, 1.26-8.90]; P=0.015). Phenotypes and association of clusters with specific outcomes were reproduced in an independent validation cohort (n=262). CONCLUSIONS: Unsupervised cluster analysis of patients with AS revealed 3 distinct groups with different causes of death. This provides a new perspective in the categorization of patients with AS that takes into account comorbidities and extravalvular cardiac dysfunction.

Different effects of SGLT2 inhibitors according to the presence and types of heart failure in type 2 diabetic patients.

BACKGROUND: The effects of sodium-glucose cotransporter 2 inhibitor (SGLT2i) on cardiac function are not fully understood. We investigated the changes in cardiac function in diabetic patients according to the presence and types of heart failure (HF). METHODS: We retrospectively identified 202 diabetic patients who underwent echocardiography before, and 6 to 24 months after the initiation of SGLT2i. After propensity score matching with diabetic patients without SGLT2i, the study population (n = 304) were categorized into group 1 (without HF nor SGLT2i; n = 76), group 2 (without HF and received SGLT2i; n = 78), group 3 (with HF but without SGLT2i; n = 76), and group 4 (with HF and received SGLT2i; n = 74). Changes in echocardiographic parameters were compared between these 4 groups, and between HF patients with reduced versus preserved ejection fraction (EF). RESULTS: After a median 13 months of follow-up, HF patients with SGLT2i showed a significant decrease in left ventricular end-diastolic dimension (LV-EDD; from 57.4 mm [50.0-64.9] to 53.0 mm [48.0-60.0]; p < 0.001) and improvement in LV-EF (from 36.1% [25.6-47.5] to 45.0% [34.8-56.3]; p < 0.001). LV mass index and diastolic parameters also showed improvements in HF patients with SGLT2i. The SGLT2i-induced improvements in cardiac function were more prominent in HF patients than those without HF, and in HFrEF patients than HFpEF patients. CONCLUSIONS: Use of SGLT2i improved cardiac function in diabetic patients, regardless of the presence of HF. The improvements were more prominent in HF patients, especially in those with HFrEF. These improvements in cardiac function would contribute to the clinical benefit of SGLT2i.

Myocardial structural and functional changes in patients with liver cirrhosis awaiting liver transplantation: a comprehensive cardiovascular magnetic resonance and echocardiographic study.

BACKGROUND: Cardiac dysfunction is increasingly recognized in patients with liver cirrhosis. Nevertheless, the presence or absence of structural alterations such as diffuse myocardial fibrosis remains unclear. We aimed to investigate myocardial structural changes in cirrhosis, and explore left ventricular (LV) structural and functional changes induced by liver transplantation. METHODS: This study included 33 cirrhosis patients listed for transplantation and 20 healthy controls. Patients underwent speckle-tracking echocardiography and cardiovascular magnetic resonance (CMR) with extracellular volume fraction (ECV) quantification at baseline (n = 33) and 1 year after transplantation (n = 19). RESULTS: CMR-based LV ejection fraction (CMRLV-EF) and echocardiographic LV global longitudinal strain (LV-GLS) demonstrated hyper-contractile LV in cirrhosis patients (CMRLV-EF: 67.8 ± 6.9% in cirrhosis vs 63.4 ± 6.4% in healthy controls, P = 0.027; echocardiographic GLS: - 24.2 ± 2.7% in cirrhosis vs - 18.6 ± 2.2% in healthy controls, P < 0.001). No significant differences in LV size, wall thickness, mass index, and diastolic function between cirrhosis patients and healthy controls were seen (all P > 0.1). Only one of the cirrhosis patients showed late gadolinium enhancement. However, cirrhosis patients showed a higher ECV (31.6 ± 5.1% vs 25.4 ± 1.9%, P < 0.001) than healthy controls. ECV showed a positive correlation with Child-Pugh score (r = 0.564, P = 0.001). Electrocardiogram-based corrected QT interval was prolonged in cirrhosis (P < 0.001). One-year post-transplantation, echocardiographic LV-GLS (from - 24.9 ± 2.4% to - 20.6 ± 3.4%, P < 0.001) and ECV (from 30.9 ± 4.5% to 25.4 ± 2.6%, P = 0.001) moved to the normal ranges. Corrected QT interval decreased after transplantation (from 475 ± 41 to 429 ± 30 msec, P = 0.001). CONCLUSIONS: Myocardial extracellular volume expansion with augmented resting LV systolic function was characteristic of cirrhotic cardiomyopathy, which normalizes 1-year post-transplantation. Thus, myocardial extracellular expansion represents a structural component of myocardial changes in cirrhosis.

Pittsburgh B Compound Positron Emission Tomography in Patients With AL Cardiac Amyloidosis.

BACKGROUND: It remains unknown whether the noninvasive evaluation of the degree of amyloid deposition in the myocardium can predict the prognosis of patients with light chain (AL) cardiac amyloidosis. OBJECTIVES: The purpose of this study was to demonstrate that 11C-Pittsburgh B compound positron emission tomography (11C-PiB PET) is useful for prognostication of AL cardiac amyloidosis by noninvasively imaging the myocardial AL amyloid deposition. METHODS: This study consecutively enrolled 41 chemotherapy-naïve AL cardiac amyloidosis patients. The amyloid deposit was quantitatively assessed with amyloid P immunohistochemistry in endomyocardial biopsy specimens and was compared with the degree of myocardial 11C-PiB uptake on PET. The primary endpoint was a composite of all-cause death, heart transplantation, and acute decompensated heart failure. RESULTS: The degree of myocardial 11C-PiB PET uptake was significantly higher in the cardiac amyloidosis patients compared with normal subjects and correlated well with the degree of amyloid deposit on histology (R2 = 0.343, p < 0.001). During follow-up (median: 423 days, interquartile range: 93 to 1,222 days), 24 patients experienced the primary endpoint. When the cardiac amyloidosis patients were divided into tertiles by the degree of myocardial 11C-PiB PET uptake, patients with the highest PiB uptake experienced the worst clinical event-free survival (log-rank p = 0.014). The degree of myocardial PiB PET uptake was a significant predictor of clinical outcome on multivariate Cox regression analysis (adjusted hazard ratio: 1.185; 95% confidence interval: 1.054 to 1.332; p = 0.005). CONCLUSIONS: These proof-of-concept results show that noninvasive evaluation of myocardial amyloid load by 11C-PiB PET reflects the degree of amyloid deposit and is an independent predictor of clinical outcome in AL cardiac amyloidosis patients.

Aortic valve replacement-induced changes in native T1 are related to prognosis in severe aortic stenosis: T1 mapping cardiac magnetic resonance imaging study.

AIMS: Native T1 times from T1 mapping cardiac magnetic resonance (CMR) are associated with myocardial fibrosis in aortic stenosis (AS). We investigated whether changing patterns in native T1 predict clinical outcomes after aortic valve replacement (AVR) in severe AS patients. METHODS AND RESULTS: Forty-three patients with severe AS (65.9 ± 8.1 years; 24 men) who underwent T1 mapping CMR at baseline and 1 year after AVR were prospectively enrolled. Upper limit of native T1 from healthy volunteers was used to define normal myocardium and diffuse fibrosis (native T1 < 1208.4 and ≥1208.4 ms, respectively). Participants were categorized into Group 1 (pre- and post-AVR normal myocardium; n = 11), Group 2 (pre-AVR diffuse fibrosis and post-AVR normal myocardium; n = 18), and Group 3 (post-AVR diffuse fibrosis; n = 14). Native T1 significantly decreased 1 year after AVR (pre-AVR, 1233.8 ± 49.7 ms; post-AVR, 1189.1 ± 58.4 ms; P < 0.001), which was associated with left ventricular (LV) mass regression (△native T1 vs. △LV mass index, r = 0.454, P = 0.010) and systolic function improvement (△native T1 vs. △LV ejection fraction, r = -0.379, P = 0.012). Group 2 showed greater functional improvements, whereas these benefits were blunted in Group 3. Group 3 had significantly worse outcomes than Group 1 [hazard ratio (HR), 9.479, 95% confidence interval (CI) 1.176-76.409; P = 0.035] and Group 2 (HR 3.551, 95% CI 1.178-10.704; P = 0.024). CONCLUSION: AVR-induced changes in native T1 values are associated with LV systolic functional changes as well as prognosis in severe AS. Post-AVR T1 mapping CMR can be used as an imaging biomarker.

Derivation and validation of a mortality risk prediction model using global longitudinal strain in patients with acute heart failure.

AIMS: To develop a mortality risk prediction model in patients with acute heart failure (AHF), using left ventricular (LV) function parameters with clinical factors. METHODS AND RESULTS: In total, 4312 patients admitted for AHF were retrospectively identified from three tertiary centres, and echocardiographic parameters including LV ejection fraction (LV-EF) and LV global longitudinal strain (LV-GLS) were measured in a core laboratory. The full set of risk factors was available in 3248 patients. Using Cox proportional hazards model, we developed a mortality risk prediction model in 1859 patients from two centres (derivation cohort) and validated the model in 1389 patients from one centre (validation cohort). During 32 (interquartile range 13-54) months of follow-up, 1285 patients (39.6%) died. Significant predictors for mortality were age, diabetes, diastolic blood pressure, body mass index, natriuretic peptide, glomerular filtration rate, failure to prescribe beta-blockers, failure to prescribe renin-angiotensin system blockers, and LV-GLS; however, LV-EF was not a significant predictor. Final model including these predictors to estimate individual probabilities of mortality had C-statistics of 0.75 [95% confidence interval (CI) 0.73-0.78; P < 0.001] in the derivation cohort and 0.78 (95% CI 0.75-0.80; P < 0.001) in the validation cohort. The prediction model had good performance in both heart failure (HF) with reduced EF, HF with mid-range EF, and HF with preserved EF. CONCLUSION: We developed a mortality risk prediction model for patients with AHF incorporating LV-GLS as the LV function parameter, and other clinical factors. Our model provides an accurate prediction of mortality and may provide reliable risk stratification in AHF patients.

Changes of echocardiographic parameters in primary mitral regurgitation and determinants of symptom: an assessment from the Asian Valve Registry data.

Clinicians often have a difficulty in determining the presence of mitral regurgitation (MR)-related symptoms because of subjectivity. However, there are few actual measurement data for echocardiographic left ventricular (LV) and left atrial (LA) size related to the severity of MR and the relationship between MR-related symptoms and these echocardiographic parameters. Among patients enrolled in the Asian Valve Registry, we investigated 778 consecutive patients with primary MR showing sinus rhythm. Symptoms were determined by New York Heart Association grade (≤ II or ≥ III). MR severity was mild in 106, moderate in 285, and severe in 387 patients. LA volume index, LV end-diastolic diameter, and LV mass index increased with increasing MR grade [LA volume index: 47.9 (mild), 56.2 (moderate), and 64.9 ml/m2 (severe) (p < 0.001), LV end-diastolic diameter: 51.2, 54.5, 58.1 mm (p < 0.001), and LV mass index: 101, 109, 123 g/m2 (p < 0.001)]. Regarding moderate and severe MR, 70 patients (10.4%) were symptomatic. In multivariable analysis, for being symptomatic in moderate and severe MR patients, LV mass index (odds ratio [OR] per 10 g/m2 increment; 1.09; 95% confidence interval [CI]: 1.005-1.18, p = 0.040), ejection fraction (OR per 1% increment; 0.96, 95%CI: 0.93-0.98, p < 0.001), female gender (OR 2.28; 95% CI: 1.31-3.98, p = 0.004), and heart rate (OR per 1 bpm increment; 1.03; 95%CI: 1.01-1.05, p = 0.007) were independent factors. LV and LA parameters on echocardiography worsened as MR severity progressed. Larger LV mass index and lower ejection fraction were independent determinant factors for MR-related symptoms. We should also pay attention to LV hypertrophy in patients with primary MR.

Clinical Usefulness of Pressure Recovery Adjustment in Patients with Predominantly Severe Aortic Stenosis: Asian Valve Registry Data.

BACKGROUND: Adjustment for pressure recovery (PR) may reconcile discrepancies in pressure gradients measured by Doppler echocardiography and direct catheterization in patients with mild to moderately severe aortic stenosis (AS). The aim of this study was to evaluate whether PR adjustment is useful in a large cohort of predominantly patients with severe AS. METHODS: Data from 697 patients (mean age 70 ± 11 years) in the Asian Valve Registry with a mean aortic valve area (AVA) of 0.8 ± 0.3 cm2 and a mean gradient of 46 ± 21 mm Hg were analyzed. PR-adjusted AVAs were calculated using validated equations. The primary outcome included aortic valve replacement, all-cause mortality, and hospitalization for heart failure during the median follow-up period of 2.9 years. RESULTS: Before PR adjustment, 521 patients showed AVA values of ≤1.0 cm2, and after PR adjustment, 129 (24.8%) were reclassified to moderate AS with a mean AVA of 1.1 ± 0.1 cm2. PR adjustment decreased the frequency of low-gradient severe AS (AVA ≤ 1.0 cm2 and mean gradient < 40 mm Hg) from 22.4% (156 of 697) to 10.2% (71 of 697). Most reclassification (>95%) occurred in patients with aortic dimensions < 3.5 cm, mean gradients < 60 mm Hg, or AVAs between 0.8 and 1.0 cm2. Patients with reclassification to moderate AS after PR adjustment showed higher 4-year clinical event-free survival rates (46.2 ± 4.9% vs 14.6 ± 2.1% in patients with severe AS after PR adjustment, P < .001). Cox regression analysis showed that reclassification after PR adjustment had additive value to predict the primary outcome (hazard ratio, 0.678; 95% CI, 0.467-0.985; P = .041) and aortic valve replacement (hazard ratio, 0.663; 95% CI, 0.440-0.998; P = .049). CONCLUSIONS: Clinically relevant PR frequently occurs in patients with moderate to severe AS. PR adjustment has prognostic implications, and accurate classification of severe AS can help prevent discordant AS grading.

Healthcare utilization, medical expenditure, and mortality in Korean patients with pulmonary hypertension.

BACKGROUND: Limited data exists regarding healthcare utilization, medical expenses, and prognosis of pulmonary hypertension (PH) according to the World Health Organization (WHO) classification. We aimed to investigate mortality risk, healthcare utilization and medical expenditure in patients with PH across the five diagnostic subgroups. METHODS: We identified 2185 patients with PH, defined as peak tricuspid regurgitation velocity > 3.4 m/sec, among the consecutive patients referred for echocardiography between 2009 and 2015. Using diagnostic codes, medical records, and echocardiographic findings, the enrolled patients were classified according to the five subgroups by WHO classification. Healthcare utilization, costs, and all-cause mortality were assessed. RESULTS: Diagnostic subgroups of PH demonstrated significantly different clinical features. During a median of 32.4 months (interquartile range, 16.2-57.8), 749 patients (34.3%) died. Mortality risk was the lowest in group II (left heart disease) and highest in group III (chronic lung disease). The etiologies of pulmonary arterial hypertension (PAH) had significant influence on the mortality risk in group I, showing the worst prognosis in PAH associated with connective tissue disease. Medical expenditure and healthcare utilization were different between the PH subgroups: groups II and V had more hospitalizations and medical expenses than other groups. Regardless of PH subgroups, the severity of PH was associated with higher mortality risk, more healthcare utilization and medical expenditure. CONCLUSIONS: Significant differences in clinical features and prognostic profiles between PH subgroups reflect the differences in pathophysiology and clinical consequences. Our findings highlight the importance of comprehensive understanding of PH according to the etiology and its severity.