Association of Adenoma Detection Rate and Adenoma Characteristics With Colorectal Cancer Mortality After Screening Colonoscopy.

BACKGROUND & AIMS: The adenoma detection rate (ADR) and characteristics of previously resected adenomas are associated with colorectal cancer (CRC) incidence and mortality. However, the combined effect of both factors on CRC mortality is unknown. PATIENTS AND METHODS: Using data of the Austrian quality assurance program for screening colonoscopy, we evaluated the combined effect of ADR and lesion characteristics on subsequent risk for CRC mortality. We analyzed mortality rates for individuals with low-risk adenomas (1-2 adenomas <10 mm), individuals with high-risk adenomas (advanced adenomas or ≥3 adenomas), and after negative colonoscopy (negative colonoscopy or small hyperplastic polyps) performed by endoscopists with an ADR <25% compared with ≥25%. Cox regression was used to determine the association of combined risk groups with CRC mortality, adjusted for age and sex. RESULTS: We evaluated 259,885 colonoscopies performed by 361 endoscopists. A total of 165 CRC-related deaths occurred during the follow-up period, up to 12.2 years. In all risk groups, CRC mortality was higher when colonoscopy was performed by an endoscopist with an ADR <25%. Compared with negative colonoscopy with an ADR ≥25%, CRC mortality was similar for individuals with low-risk adenomas irrespective of ADR (for ADR ≥25%: adjusted hazard ratio [HR], 1.22; 95% confidence interval [CI], 0.59-2.49; for ADR <25%: adjusted HR, 1.25; 95% CI, 0.64-2.43) and after negative colonoscopy with ADR <25% (adjusted HR, 1.27; 95% CI, 0.81-2.00). Individuals with high-risk adenomas were at significantly higher risk for CRC death if colonoscopy was performed by an endoscopist with an ADR <25% (adjusted HR, 2.25; 95% CI, 1.18-4.31) but not if performed by an endoscopist with an ADR ≥25% (adjusted HR, 1.35; 95% CI, 0.61-3.02). CONCLUSIONS: Our study adds important evidence for mandatory assessment and monitoring of performance quality in screening colonoscopy. High-quality colonoscopy was associated with a lower risk for CRC death, and the impact of ADR was strongest for individuals with high-risk adenomas.

Feature Tracking of Global Longitudinal Strain by Using Cardiovascular MRI Improves Risk Stratification in Heart Failure with Preserved Ejection Fraction.

Background In heart failure with preserved ejection fraction (HFpEF), echocardiographic studies suggest that global longitudinal strain (GLS) has an impact on survival. Feature-tracking cardiovascular MRI also allows for strain analysis; however, to the knowledge of the authors, little is known about its prognostic value and whether it reflects severity of diffuse fibrosis, as assessed by cardiovascular MRI T1 mapping. Purpose To investigate the association between myocardial strain at cardiovascular MRI with extracellular volume by T1 mapping and outcome in participants with HFpEF. Materials and Methods In this secondary analysis of a prospective study (NCT03405987), consecutive participants with HFpEF underwent cardiovascular MRI between July 2012 and March 2018, including T1 mapping and three-dimensional strain analysis. Extracellular volume and strain results were assessed to determine if there was a correlation between these two factors. Cox regression was performed to determine the prognostic relevance of MRI-derived myocardial strain for a combined end point (events) of heart failure hospitalizations and cardiovascular death. Results In total, 206 consecutive participants with HFpEF (mean age, 71 years ± 8 [standard deviation]; 69% women) were included. Median myocardial global longitudinal strain (GLS) at MRI was -8.5% and showed low correlation with extracellular volume (r = 0.28; P = .003). A total of 109 events (53%) were recorded during a follow-up of 38 months ± 29. Participants with a GLS above the median had higher event rates (log-rank test, P < .001). By multivariable Cox regression analysis, GLS remained independently associated with outcome (hazard ratio, 1.06 per 1% strain increase; 95% confidence interval: 1.01, 1.11; P = .03) when corrected for risk factors including age, diabetes, renal function, N-terminal pro-b-type natriuretic peptide serum concentration, and right ventricular size and function. Conclusion In participants with heart failure with preserved ejection fraction, global longitudinal strain at cardiovascular MRI was correlated with extracellular volume by T1 mapping and was associated with cardiovascular events. © RSNA, 2020 Online supplemental material is available for this article.

Persistent atrial fibrillation in heart failure with preserved ejection fraction: Prognostic relevance and association with clinical, imaging and invasive haemodynamic parameters.

BACKGROUND: Atrial fibrillation (AF) is a frequent finding in HFpEF. However, its association with invasive haemodynamics, imaging parameters and outcome in HFpEF is not well established. Furthermore, the relevance of AF subtype with regard to outcome is unclear. This study sought to investigate the prognostic impact of paroxysmal and persistent AF in a well-defined heart failure with preserved ejection fraction (HFpEF) population. MATERIALS AND METHODS: Between 2010 and 2016, 254 HFpEF patients were prospectively enrolled. All patients underwent echocardiography as well as left and right heart catheterization. Patients without contraindications underwent CMR including T1 mapping. Follow-up and outcome data were collected. Patients with significant coronary artery disease were excluded. RESULTS: A total of 153 patients (60%) suffered from AF, 119 (47%) had persistent and 34 (13%) had paroxysmal AF. By multiple logistic regression analysis, persistent AF was independently associated with NT-proBNP (P = .003), NYHA functional class (P = .040), left and right atrial size (P = .022 and <.001, respectively), cardiac output (P = .002) and COPD (P = .034). After a median follow-up of 23 months (interquartile range 5-48), 92 patients (36%) reached the primary end point defined as hospitalization for heart failure or cardiovascular death. By multivariate Cox regression analysis, only persistent AF (P = .005) and six-minute walk distance (P = .011) were independently associated with the primary end point. CONCLUSIONS: Sixty percent of our HFpEF patients suffered from AF. Persistent but not paroxysmal AF was strongly associated with event-free survival and was independently related to NYHA functional class, serum NT-proBNP, atrial size, cardiac ouput and presence of COPD.

Diameter of the Pulmonary Artery in Relation to the Ascending Aorta: Association with Cardiovascular Outcome.

Purpose To investigate whether the pulmonary artery (PA)-to-ascending aorta (Ao) ratio is associated with outcome in unselected patients referred for cardiac magnetic resonance (MR) imaging. Materials and Methods This study prospectively enrolled 650 consecutive patients (47.2% women; mean age, 56.1 years ± 17.7 [standard deviation]). Diameters of PA and Ao were measured in axial black blood images. On the basis of previous results, a PA-to-Ao ratio of 1.0 or greater was chosen as the cutoff for further analysis. Univariable and multivariable Cox regression models were used to investigate the primary end point, which was defined as a composite of cardiovascular hospitalization and death. Results A PA-to-Ao ratio of 1.0 or greater was present in 131 (20.2%) patients. Patients with a PA-to-Ao ratio of 1.0 or greater were predominantly women (P = .010); more frequently presented with atrial fibrillation (P < .001), diabetes (P < .001), and impaired renal function (P < .001); and had higher N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels (P < .001), larger left (P = .023) and right ventricles (RV; P = .002), and worse RV function (P < .001). Patients were followed for 17.8 months ± 12.9, during which 110 patients (16.9%) reached the primary end point. By Kaplan-Meier analysis, event-free survival was significantly worse in patients with a PA-to-Ao ratio of 1.0 or greater (log-rank test, P < .001). A PA-to-Ao ratio of 1.0 or greater was independently associated with outcome by multivariable Cox regression analysis, in addition to age, NT-proBNP serum levels, and RV size. Conclusion A PA-to-Ao ratio of 1.0 or greater identified patients at risk, most likely because of elevated PA pressures. On the basis of these results, the PA-to-Ao ratio should routinely be reported at cardiac MR imaging. © RSNA, 2017 Online supplemental material is available for this article.

Pulmonary artery to aorta ratio for the detection of pulmonary hypertension: cardiovascular magnetic resonance and invasive hemodynamics in heart failure with preserved ejection fraction.

BACKGROUND: Previous work indicates that dilatation of the pulmonary artery (PA) itself or in relation to the ascending aorta (PA:Ao ratio) predicts pulmonary hypertension (PH). Whether these results also apply for heart failure with preserved ejection fraction (HFpEF) is unknown. In the present study we evaluated the diagnostic and prognostic power of PA diameter and PA:Ao ratio on top of right ventricular (RV) size, function, and septomarginal trabeculation (SMT) thickness by cardiovascular magnetic resonance (CMR) in HFpEF. METHODS AND RESULTS: 159 consecutive HFpEF patients were prospectively enrolled. Of these, 111 underwent CMR and invasive hemodynamic evaluation. By invasive assessment 64 % of patients suffered from moderate/severe PH (mean pulmonary artery pressure (mPAP) ≥30 mmHg). Significant differences between groups with and without moderate/severe PH were observed with respect to PA diameter (30.9 ± 5.1 mm versus 26 ± 5.1 mm, p < 0.001), PA:Ao ratio (0.93 ± 0.16 versus 0.78 ± 0.14, p < 0.001), and SMT diameter (4.6 ± 1.5 mm versus 3.8 ± 1.2 mm; p = 0.008). The strongest correlation with mPAP was found for PA:Ao ratio (r = 0.421, p < 0.001). By ROC analysis the best cut-off for the detection of moderate/severe PH was found for a PA:Ao ratio of 0.83. Patients were followed for 22.0 ± 14.9 months. By Kaplan Meier analysis event-free survival was significantly worse in patients with a PA:Ao ratio ≥0.83 (log rank, p = 0.004). By multivariable Cox-regression analysis PA:Ao ratio was independently associated with event-free survival (p = 0.003). CONCLUSION: PA:Ao ratio is an easily measureable noninvasive indicator for the presence and severity of PH in HFpEF, and it is related with outcome.

DPD Quantification Correlates With Extracellular Volume and Disease Severity in Wild-Type Transthyretin Cardiac Amyloidosis.

Background: The pathophysiological hallmark of wild-type transthyretin amyloid cardiomyopathy (ATTRwt-CM) is the deposition of amyloid within the myocardium. Objectives: This study aimed to investigate associations between quantitative cardiac 99mTc-3,3-diphosphono-1,2-propanodicarboxylic acid (DPD) uptake and myocardial amyloid burden, cardiac function, cardiac biomarkers, and clinical status in ATTRwt-CM. Methods: Forty ATTRwt-CM patients underwent quantitative DPD single photon emission computed tomography/computed tomography to determine the standardized uptake value (SUV) retention index, cardiac magnetic resonance imaging to determine extracellular volume (ECV) and cardiac function (RV-LS), and assessment of cardiac biomarkers (N-terminal prohormone of brain natriuretic peptide [NT-proBNP], troponin T) and clinical status (6-minute walk distance [6MWD], National Amyloidosis Centre [NAC] stage). ATTRwt-CM patients were divided into 2 cohorts based on median SUV retention index (low uptake: <5.19 mg/dL, n = 20; high uptake: ≥5.19 mg/dL, n = 20). Linear regression models were used to assess associations of the SUV retention index with variables of interest and the Mann-Whitney U or chi-squared test to compare variables between groups. Results: ATTRwt-CM patients (n = 40) were elderly (78.0 years) and predominantly male (75.0%). Univariable linear regression analyses revealed associations of the SUV retention index with ECV (r = 0.669, ß = 0.139, P < 0.001), native T1 time (r = 0.432, ß = 0.020, P = 0.005), RV-LS (r = 0.445, ß = 0.204, P = 0.004), NT-proBNP (log10) (r = 0.458, ß = 2.842, P = 0.003), troponin T (r = 0.422, ß = 0.048, P = 0.007), 6MWD (r = 0.385, ß = -0.007, P = 0.017), and NAC stage (r = 0.490, ß = 1.785, P = 0.001). Cohort comparison demonstrated differences in ECV (P = 0.001), native T1 time (P = 0.013), RV-LS (P = 0.003), NT-proBNP (P < 0.001), troponin T (P = 0.046), 6MWD (P = 0.002), and NAC stage (I: P < 0.001, II: P = 0.030, III: P = 0.021). Conclusions: In ATTRwt-CM, quantitative cardiac DPD uptake correlates with myocardial amyloid load, longitudinal cardiac function, cardiac biomarkers, exercise capacity, and disease stage, providing a valuable tool to quantify and monitor cardiac disease burden.

Native skeletal muscle T1-time on cardiac magnetic resonance: A predictor of outcome in patients with heart failure with preserved ejection fraction.

BACKGROUND: Heart failure with preserved ejection fraction (HFpEF) is associated with heart failure (HF) hospitalizations and death. Previous studies have shown that altered muscle composition is associated with higher risk of adverse outcome in HFpEF patients. AIM: The purpose of our study was to investigate the association between skeletal muscle composition, as measured by skeletal muscle T1-times on cardiac magnetic resonance (CMR) imaging, and adverse outcome. METHODS: We measured skeletal muscle T1-times of the back muscles on standard CMR images in a prospective cohort of HFpEF patients. Cox regression models were used to test the association of skeletal muscle T1-times and adverse outcome defined as hospitalization for HF and/or cardiovascular death. RESULTS: We included 101 patients (mean age 72±7 years, 71 % female) in our study. The median skeletal muscle T1-times were 842 ms (IQR 806-881 ms). In univariate analysis high muscle T1-time was associated with adverse outcome (HR=1.96 [95 % CI, 1.31-2.94] per every 100 ms increase; p=.001). After adjustment for age, sex, body mass index, left- and right ventricular ejection fraction, N-terminal pro-brain natriuretic peptide and myocardial native T1-times, native skeletal muscle T1-time remained an independent predictor for adverse outcome (HR=1.94 [95 % CI, 1.24-3.03] per every 100 ms increase; p=.004). CONCLUSION: In patients with HFpEF, high skeletal muscle T1-times on standard CMR scans are associated with higher rates of HF hospitalizations and cardiovascular death. CONDENSED ABSTRACT: Skeletal muscle abnormalities are common in patients with heart failure with preserved ejection fraction (HFpEF). The present study evaluates skeletal muscle composition, as quantified by native skeletal muscle T1-times of the back muscles on standard cardiac magnetic resonance imaging, and assessed the association with adverse outcome, defined as hospitalization for heart failure and/or cardiovascular death. In a prospective cohort of 101 patients with HFpEF, we found that high native skeletal muscle T1-times are associated with an increased risk for adverse outcome. These findings suggest that native skeletal muscle T1-time may serve as marker for improved risk prediction.

Management of Fluid Overload in Patients With Severe Aortic Stenosis (EASE-TAVR): A Randomized Controlled Trial.

BACKGROUND: Fluid overload (FO) subjects patients with severe aortic stenosis (AS) to increased risk for heart failure and death after valve replacement and can be objectively quantified using bioimpedance spectroscopy (BIS). OBJECTIVES: The authors hypothesized that in AS patients with concomitant FO, BIS-guided decongestion could improve prognosis and quality of life following transcatheter aortic valve replacement (TAVR). METHODS: This randomized, controlled trial enrolled 232 patients with severe AS scheduled for TAVR. FO was defined using a portable whole-body BIS device according to previously established cutoffs (≥1.0 L and/or ≥7%). Patients with FO (n = 111) were randomly assigned 1:1 to receive BIS-guided decongestion (n = 55) or decongestion by clinical judgment alone (n = 56) following TAVR. Patients without FO (n = 121) served as a control cohort. The primary endpoint was the composite of hospitalization for heart failure and/or all-cause death at 12 months. The secondary endpoint was the change from baseline to 12 months in the Kansas City Cardiomyopathy Questionnaire. RESULTS: The occurrence of the primary endpoint at 12 months was significantly lower in the BIS-guided vs the non-BIS-guided decongestion group (7/55 [12.7%, all deaths] vs 18/56 [32.1%, 9 hospitalizations for heart failure and 9 deaths]; HR: 0.36; 95% CI: 0.15-0.87; absolute risk reduction = -19.4%). Outcomes in the BIS-guided decongestion group were identical to the euvolemic control group (log-rank test, P = 0.7). BIS-guided decongestion was also associated with a higher increase in the Kansas City Cardiomyopathy Questionnaire score from baseline compared to non-BIS-guided decongestion (P = 0.001). CONCLUSIONS: In patients with severe AS and concomitant FO, quantitatively guided decongestive treatment and associated intensified management post-TAVR was associated with improved outcomes and quality of life compared to decongestion by clinical judgment alone. (Management of Fluid Overload in Patients Scheduled for Transcatheter Aortic Valve Replacement [EASE-TAVR]; NCT04556123).

Impact of right ventricular-to-pulmonary artery coupling on remodeling and outcome in patients undergoing transcatheter edge-to-edge mitral valve repair.

BACKGROUND: Right ventricular-to-pulmonary artery (RV-PA) coupling has recently been shown to be associated with outcome in valvular heart disease. However, longitudinal data on RV dysfunction and reverse cardiac remodeling in patients following transcatheter edge-to-edge mitral valve repair (M-TEER) are scarce. METHODS: Consecutive patients with primary as well as secondary mitral regurgitation (MR) were prospectively enrolled and had comprehensive echocardiographic and invasive hemodynamic assessment at baseline. Kaplan-Meier estimates and multivariable Cox-regression analyses were performed, using a composite endpoint of heart failure hospitalization and death. RESULTS: Between April 2018 and January 2021, 156 patients (median 78 y/o, 55% female, EuroSCORE II: 6.9%) underwent M-TEER. On presentation, 64% showed impaired RV-PA coupling defined as tricuspid annular plane systolic excursion to pulmonary artery systolic pressure (TAPSE/PASP) ratio < 0.36. Event-free survival rates at 2 years were significantly lower among patients with impaired coupling (57 vs. 82%, p < 0.001), both in patients with primary (64 vs. 91%, p = 0.009) and secondary MR (54 vs. 76%, p = 0.026). On multivariable Cox-regression analyses adjusted for baseline, imaging, hemodynamic, and procedural data, TAPSE/PASP ratio < 0.36 was independently associated with outcome (adj.HR 2.74, 95% CI 1.17-6.43, p = 0.021). At 1-year follow-up, RV-PA coupling improved (TAPSE: ∆ + 3 mm, PASP: ∆ - 10 mmHg, p for both < 0.001), alongside with a reduction in tricuspid regurgitation (TR) severity (grade ≥ II: 77-54%, p < 0.001). CONCLUSIONS: TAPSE/PASP ratio was associated with outcome in patients undergoing M-TEER for primary as well as secondary MR. RV-PA coupling, alongside with TR severity, improved after M-TEER and might thus provide prognostic information in addition to established markers of poor outcome.

Quantitative fluid overload in severe aortic stenosis refines cardiac damage and associates with worse outcomes.

AIMS: Cardiac decompensation in aortic stenosis (AS) involves extra-valvular cardiac damage and progressive fluid overload (FO). FO can be objectively quantified using bioimpedance spectroscopy. We aimed to assess the prognostic value of FO beyond established damage markers to guide risk stratification. METHODS AND RESULTS: Consecutive patients with severe AS scheduled for transcatheter aortic valve implantation (TAVI) underwent prospective risk assessment with bioimpedance spectroscopy (BIS) and echocardiography. FO by BIS was defined as ≥1.0 L (0.0 L = euvolaemia). The extent of cardiac damage was assessed by echocardiography according to an established staging classification. Right-sided cardiac damage (rCD) was defined as pulmonary vasculature/tricuspid/right ventricular damage. Hospitalization for heart failure (HHF) and/or death served as primary endpoint. In total, 880 patients (81 ± 7 years, 47% female) undergoing TAVI were included and 360 (41%) had FO. Clinical examination in patients with FO was unremarkable for congestion signs in >50%. A quarter had FO but no rCD (FO+/rCD-). FO+/rCD+ had the highest damage markers, including N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels. After 2.4 ± 1.0 years of follow-up, 236 patients (27%) had reached the primary endpoint (29 HHF, 194 deaths, 13 both). Quantitatively, every 1.0 L increase in bioimpedance was associated with a 13% increase in event hazard (adjusted hazard ratio 1.13, 95% confidence interval 1.06-1.22, p < 0.001). FO provided incremental prognostic value to traditional risk markers (NT-proBNP, EuroSCORE II, damage on echocardiography). Stratification according to FO and rCD yielded worse outcomes for FO+/rCD+ and FO+/rCD-, but not FO-/rCD+, compared to FO-/rCD-. CONCLUSION: Quantitative FO in patients with severe AS improves risk prediction of worse post-interventional outcomes compared to traditional risk assessment.

Prognostic impact of left atrial function in heart failure with preserved ejection fraction in sinus rhythm vs. persistent atrial fibrillation.

AIMS: We sought to determine the prognostic impact of left atrial (LA) size and function in patients with heart failure with preserved ejection fraction (HFpEF) in sinus rhythm (SR) vs. atrial fibrillation (AF). METHODS AND RESULTS: We enrolled consecutive HFpEF patients and assessed indexed LA volumes and emptying fractions (LA-EF) on cardiac magnetic resonance imaging. In addition, all patients underwent right and left heart catheterization, 6 min walk test, and N-terminal prohormone of brain natriuretic peptide evaluation. We prospectively followed patients and used Cox regression models to determine the association of LA size and function with a composite endpoint of heart failure hospitalization and cardiovascular death. A total of 188 patients (71% female patients, 70 ± 8 years old) were included of whom 92 (49%) were in persistent AF. Sixty-five patients reached the combined endpoint during a follow-up of 31 (9-57) months. Multivariate Cox regression adjusted for established risk factors revealed that LA-EF was significantly associated with outcome in patients in SR [adjusted hazard ratio 2.14; 95% confidence interval (1.32-3.47) per 1-SD decline, P = 0.002]. In persistent AF, no LA imaging parameter was related to outcome. By receiver operating characteristic and restricted cubic spline analyses, we identified an LA-EF ≥ 40% as best indicator for favourable outcomes in patients with HFpEF and SR. Persistent AF carried a similar risk for adverse outcome compared with impaired LA-EF (<40%) in SR (log-rank, P = 0.340). CONCLUSIONS: In HFpEF patients in SR, impaired LA-EF is independently associated with worse cardiovascular outcome, which is similar to persistent AF. In persistent AF, LA parameters lose their prognostic ability.

Transcatheter Versus Surgical Valve Repair in Patients with Severe Mitral Regurgitation.

BACKGROUND: Transcatheter edge-to-edge mitral valve repair (TMVR) is increasingly performed. However, its efficacy in comparison with surgical MV treatment (SMV) is unknown. METHODS: Consecutive patients with severe mitral regurgitation (MR) undergoing TMVR (68% functional, 32% degenerative) or SMV (9% functional, 91% degenerative) were enrolled. To account for differences in baseline characteristics, propensity score matching was performed, including age, EuroSCORE-II, left ventricular ejection fraction, and NT-proBNP. A composite of heart failure (HF) hospitalization/death served as primary endpoint. Kaplan-Meier curves and Cox-regression analyses were used to investigate associations between baseline, imaging, and procedural parameters and outcome. RESULTS: Between July 2017 and April 2020, 245 patients were enrolled, of whom 102 patients could be adequately matched (73 y/o, 61% females, EuroSCORE-II: 5.7%, p > 0.05 for all). Despite matching, TMVR patients had more co-morbidities at baseline (higher rates of prior myocardial infarction, coronary revascularization, pacemakers/defibrillators, and diabetes mellitus, p < 0.009 for all). Patients were followed for 28.3 ± 27.2 months, during which 27 events (17 deaths, 10 HF hospitalizations) occurred. Postprocedural MR reduction (MR grade <2: TMVR vs. SMV: 88% vs. 94%, p = 0.487) and freedom from HF hospitalization/death (log-rank: p = 0.811) were similar at 2 years. On multivariable Cox analysis, EuroSCORE-II (adj.HR 1.07 [95%CI: 1.00-1.13], p = 0.027) and residual MR (adj.HR 1.85 [95%CI: 1.17-2.92], p = 0.009) remained significantly associated with outcome. CONCLUSIONS: In this propensity-matched, all-comers cohort, two-year outcomes after TMVR versus SMV were similar. Given the reported favorable long-term durability of TMVR, the interventional approach emerges as a valuable alternative for a substantial number of patients with functional and degenerative MR.

Prevalence and Outcomes of Cardiac Amyloidosis in All-Comer Referrals for Bone Scintigraphy.

The prevalence of cardiac amyloidosis (CA) in the general population and associated prognostic implications remain poorly understood. We aimed to identify CA prevalence and outcomes in bone scintigraphy referrals. Methods: Consecutive all-comers undergoing 99mTc-3,3-diphosphono-1,2-propanodicarboxylic-acid (99mTc-DPD) bone scintigraphy between 2010 and 2020 were included. Perugini grade 1 was defined as low-grade uptake and grade 2 or 3 as confirmed CA. All-cause mortality, cardiovascular death, and heart failure hospitalization (HHF) served as endpoints. Results: In total, 17,387 scans from 11,527 subjects (age, 61 ± 16 y; 63.0% women, 73.6% cancer) were analyzed. Prevalence of 99mTc-DPD positivity was 3.3% (n = 376/11,527; grade 1: 1.8%, grade 2 or 3: 1.5%), and was higher among cardiac than noncardiac referrals (18.2% vs. 1.7%). In individuals with more than 1 scan, progression from grade 1 to grade 2 or 3 was observed. Among patients with biopsy-proven CA, the portion of light-chain (AL)-CA was significantly higher in grade 1 than grade 2 or 3 (73.3% vs. 15.4%). After a median of 6 y, clinical event rates were: 29.4% mortality, 2.6% cardiovascular death, and 1.5% HHF, all independently predicted by positive 99mTc-DPD. Overall, adverse outcomes were driven by confirmed CA (vs. grade 0, mortality: adjusted hazard ratio [AHR] 1.46 [95% CI 1.12-1.90]; cardiovascular death: AHR 2.34 [95% CI 1.49-3.68]; HHF: AHR 2.25 [95% CI 1.51-3.37]). One-year mortality was substantially higher in cancer than noncancer patients. Among noncancer patients, also grade 1 had worse outcomes than grade 0 (HHF/death: AHR 1.45 [95% CI 1.01-2.09]), presumably because of longer observation and higher prognostic impact of early infiltration. Conclusion: Positive 99mTc-DPD was identified in a substantial number of consecutive 99mTc-DPD referrals and associated with adverse outcomes.

Invasive Hemodynamic Assessment and Procedural Success of Transcatheter Tricuspid Valve Repair-Important Factors for Right Ventricular Remodeling and Outcome.

Introduction: Severe tricuspid regurgitation (TR) is a common condition promoting right heart failure and is associated with a poor long-term prognosis. Transcatheter tricuspid valve repair (TTVR) emerged as a low-risk alternative to surgical repair techniques. However, patient selection remains controversial, particularly regarding the benefits of TTVR in patients with pulmonary hypertension (PH). Aim: We aimed to investigate the impact of preprocedural invasive hemodynamic assessment and procedural success on right ventricular (RV) remodeling and outcome. Methods: All patients undergoing TTVR with a TR reduction of ≥1 grade without precapillary or combined PH [mean pulmonary artery pressure (mPAP) ≥25 mmHg, mean pulmonary artery Wedge pressure ≤ 15 mmHg, pulmonary vascular resistance ≥3 Wood units] were assigned to the responder group. All patients with a TR reduction of ≥1 grade and precapillary or combined PH were classified as non-responders. Patients with a TR reduction ≥2 grade were directly classified as responders, and patients without TR reduction were directly assigned as non-responders. Results: A total of 107 patients were enrolled, 75 were classified as responders and 32 as non-responders. We observed evidence of significant RV reverse remodeling in responders with a decrease in RV diameters (-2.9 mm, p = 0.001) at a mean follow-up of 229 days (±219 SD) after TTVR. RV function improved in responders [fractional area change (FAC) + 5.7%, p < 0.001, RV free wall strain +3.9%, p = 0.006], but interestingly further deteriorated in non-responders (FAC -4.5%, p = 0.003, RV free wall strain -3.9%, p = 0.007). Non-responders had more persistent symptoms than responders (NYHA ≥3, 72% vs. 11% at follow-up). Subsequently, non-response was associated with a poor long-term prognosis in terms of death, heart failure (HF) hospitalization, and re-intervention after 2 years (freedom of death, HF hospitalization, and reintervention at 2 years: 16% vs. 78%, log-rank: p < 0.001). Conclusion: Hemodynamic assessment before TTVR and procedural success are significant factors for patient prognosis. The hemodynamic profiling prior to intervention is an essential component in patient selection for TTVR. The window for edge-to-edge TTVR might be limited, but timely intervention is an important factor for a better outcome and successful right ventricular reverse remodeling.

Unveiling Cardiac Amyloidosis, its Characteristics, and Outcomes Among Patients With MR Undergoing Transcatheter Edge-to-Edge MV Repair.

BACKGROUND: Mitral regurgitation (MR) and cardiac amyloidosis (CA) both primarily affect older patients. Data on coexistence and prognostic implications of MR and CA are currently lacking. OBJECTIVES: This study sought to identify the prevalence, clinical characteristics, and outcomes of MR CA compared with lone MR. METHODS: Consecutive patients undergoing transcatheter edge-to-edge repair (TEER) for MR at 2 sites were screened for concomitant CA using a multiparametric approach including core laboratory 99mTc-3,3-diphosphono-1,2-propanodicarboxylic acid bone scintigraphy and echocardiography and immunoglobulin light chain assessment. Transthyretin CA (ATTR) was diagnosed by 99mTc-3,3-diphosphono-1,2-propanodicarboxylic acid (Perugini grade 1: early infiltration; grades 2/3: clinical CA) and the absence of monoclonal protein, and light chain (AL) CA via tissue biopsy. All-cause mortality and hospitalization for heart failure (HHF) served as the endpoints. RESULTS: A total of 120 patients (age 76.9 ± 8.1 years, 55.8% male) were recruited. Clinical CA was diagnosed in 14 patients (11.7%; 12 ATTR, 1 AL, and 1 combined ATTR/AL) and early amyloid infiltration in 9 patients (7.5%). Independent predictors of MR CA were increased posterior wall thickness and the presence of a left anterior fascicular block on electrocardiography. Procedural success and periprocedural complications of TEER were similar in MR CA and lone MR (P for all = NS). After a median of 1.7 years, 25.8% had experienced death and/or HHF. MR CA had worse outcomes compared with lone MR (HR: 2.2; 95% CI: 1.0-4.7; P = 0.034), driven by a 2.5-fold higher risk for HHF (HR: 2.5; 95% CI: 1.1-5.9), but comparable mortality (HR: 1.6; 95% CI: 0.4-6.1). CONCLUSIONS: Dual pathology of MR CA is common in elderly patients with MR undergoing TEER and has worse postinterventional outcomes compared with lone MR.

Impact of afterload and infiltration on coexisting aortic stenosis and transthyretin amyloidosis.

OBJECTIVE: The coexistence of wild-type transthyretin cardiac amyloidosis (ATTR) is common in patients with severe aortic stenosis (AS) undergoing transcatheter aortic valve implantation (TAVI). However, the impact of ATTR and AS on the resultant AS-ATTR is unclear and poses diagnostic and management challenges. We therefore used a multicohort approach to evaluate myocardial structure, function, stress and damage by assessing age-related, afterload-related and amyloid-related remodelling on the resultant AS-ATTR phenotype. METHODS: We compared four samples (n=583): 359 patients with AS, 107 with ATTR (97% Perugini grade 2), 36 with AS-ATTR (92% Perugini grade 2) and 81 age-matched and ethnicity-matched controls. 99mTc-3,3-diphosphono-1,2-propanodicarboxylic acid (DPD) scintigraphy was used to diagnose amyloidosis (Perugini grade 1 was excluded). The primary end-point was NT-pro Brain Natriuretic Peptide (BNP) and secondary end-points related to myocardial structure, function and damage. RESULTS: Compared with older age controls, the three disease cohorts had greater cardiac remodelling, worse function and elevated NT-proBNP/high-sensitivity Troponin-T (hsTnT). NT-proBNP was higher in AS-ATTR (2844 (1745, 4635) ng/dL) compared with AS (1294 (1077, 1554)ng/dL; p=0.002) and not significantly different to ATTR (3272 (2552, 4197) ng/dL; p=0.63). Diastology, hsTnT and prevalence of carpal tunnel syndrome were statistically similar between AS-ATTR and ATTR and higher than AS. The left ventricular mass indexed in AS-ATTR was lower than ATTR (139 (112, 167) vs 180 (167, 194) g; p=0.013) and non-significantly different to AS (120 (109, 130) g; p=0.179). CONCLUSIONS: The AS-ATTR phenotype likely reflects an early stage of amyloid infiltration, but the combined insult resembles ATTR. Even after treatment of AS, ATTR-specific therapy is therefore likely to be beneficial.

Sex Differences in the Associations of Visceral Adipose Tissue and Cardiometabolic and Cardiovascular Disease Risk: The Framingham Heart Study.

Background Men and women are labeled as obese on the basis of a body mass index (BMI) using the same criterion despite known differences in their fat distributions. Subcutaneous adipose tissue and visceral adipose tissue (VAT), as measured by computed tomography, are advanced measures of obesity that closely correlate with cardiometabolic risk independent of BMI. However, it remains unknown whether prognostic significance of anthropometric measures of adiposity versus VAT varies in men versus women. Methods and Results In 3482 FHS (Framingham Heart Study) participants (48.1% women; mean age, 50.8±10.3 years), we tested the associations of computed tomography-based versus anthropometric measures of fat with cardiometabolic and cardiovascular disease (CVD) risk. Mean follow-up was 12.7±2.1 years. In men, VAT, as compared with BMI, had a similar strength of association with incident cardiometabolic risk factors (eg, adjusted odds ratio [OR], 2.36 [95% CI, 1.84-3.04] versus 2.66 [95% CI, 2.04-3.47] for diabetes mellitus) and CVD events (eg, adjusted hazard ratio [HR], 1.32 [95% CI, 0.97-1.80] versus 1.74 [95% CI, 1.14-2.65] for CVD death). In women, however, VAT, when compared with BMI, conferred a markedly greater association with incident cardiometabolic risk factors (eg, adjusted OR, 4.51 [95% CI, 3.13-6.50] versus 2.33 [95% CI, 1.88-3.04] for diabetes mellitus) as well as CVD events (eg, adjusted HR, 1.85 [95% CI, 1.26-2.71] versus 1.19 [95% CI, 1.01-1.40] for CVD death). Conclusions Anthropometric measures of obesity, including waist circumference and BMI, adequately capture VAT-associated cardiometabolic and cardiovascular risk in men but not in women. In women, abdominal computed tomography-based VAT measures permit more precise assessment of obesity-associated cardiometabolic and cardiovascular risk.

Transcatheter treatment by valve-in-valve and valve-in-ring implantation for prosthetic tricuspid valve dysfunction.

Valve degeneration after surgical tricuspid valve replacement or repair is frequent and may require repeat replacement/repair. For high-risk patients, transcatheter valve-in-valve and valve-in-ring procedures have emerged as valuable treatment alternatives. Preprocedural transthoracic echocardiography is the method of choice to detect malfunction of the prosthesis including degenerative stenosis and/or regurgitation requiring reintervention. Subsequently, computed tomography is helpful for detailed anatomical analysis and periprocedural planning. Device selection and sizing depend on the size and structural details of the implanted ring or prosthesis. The procedure is mainly guided by fluoroscopy; however, transesophageal echocardiography provides complementary guidance during device implantation. Preferred access route is the right femoral vein but in cases of more horizontal implants a jugular approach might be feasible. Suitable transcatheter valves are the Edwards Sapien 3 and the Medtronic Melody valves. Differences in surgical prostheses or annuloplasty implants are important for device selection, height consideration and additional ballooning prior to or after implantation. Transesophageal echocardiography postimplantation is convenient for the assessment of transvalvular gradients or paravalvular leaks.

Discordance of High-Sensitivity Troponin Assays in Patients With Suspected Acute Coronary Syndromes.

BACKGROUND: High-sensitivity cardiac troponin (hs-cTn) assays have different analytic characteristics. OBJECTIVES: The goal of this study was to quantify differences between assays for common analytical benchmarks and to determine whether they may result in differences in the management of patients with suspected acute coronary syndrome (ACS). METHODS: The authors included patients with suspected ACS enrolled in the ROMICAT (Rule Out Myocardial Infarction/Ischemia Using Computer Assisted Tomography) I and II trials, with blood samples taken at emergency department presentation (ROMICAT-I and -II) or at 2 and 4 h thereafter (ROMICAT-II). hs-cTn concentrations were measured using 3 assays (Roche Diagnostics, Elecsys 2010 platform; Abbott Diagnostics, ARCHITECT i2000SR; Siemens Diagnostics, HsVista). Per blood sample, we determined concordance across analytic benchmarks (99th percentile). Per-patient, the authors determined concordance of management recommendations (rule-out/observe/rule-in) per the 0/2-h algorithm, and their association with diagnostic test findings (coronary artery stenosis >50% on coronary computed tomography angiography or inducible ischemia on perfusion imaging) and ACS. RESULTS: Among 1,027 samples from 624 patients (52.8 ± 10.0 years; 39.4% women), samples were classified as 99th percentile (7.2% vs. 6.0% vs. 6.2%) by Roche, Abbott, and Siemens, respectively. A total of 37.4% (n = 384 of 1,027) of blood samples were classified into the same analytical benchmark category, with low concordance across benchmarks (99th percentile 43.6%). Serial samples were available in 242 patients (40.1% women; mean age: 52.8 ± 8.0 years). The concordance of management recommendations across assays was 74.8% (n = 181 of 242) considering serial hs-cTn measurements. Of patients who were recommended to discharge, 19.6% to 21.1% had positive diagnostic test findings and 2.8% to 4.3% had ACS at presentation. CONCLUSIONS: Caregivers should be aware that there are significant differences between hs-cTn assays in stratifying individual samples and patients with intermediate likelihood of ACS according to analytical benchmarks that may result in different management recommendations. (Rule Out Myocardial Infarction by Computer Assisted Tomography [ROMICAT]; NCT00990262) (Multicenter Study to Rule Out Myocardial Infarction by Cardiac Computed Tomography [ROMICAT-II]; NCT01084239).

Heart failure with preserved ejection fraction after left-sided valve surgery: prevalent and relevant.

AIMS: To investigate the epidemiological and prognostic relationship between heart failure with preserved ejection fraction (HFpEF) and left-sided valve surgery using all-cause mortality as a primary endpoint. METHODS AND RESULTS: We studied a total of 973 patients, of whom 673 had undergone left-sided valve surgery (time from surgery to enrolment 50 ± 30 months after valve surgery) and 300 patients with HFpEF without prior surgery served as control group. Among patients after surgery, 67.4% fulfilled all criteria of HFpEF according to current guideline recommendations, 20.6% had no heart failure (HF), and 12.0% had HF with mid-range or reduced ejection fraction (HFmrEF/HFrEF). During 83 ± 39 months of follow-up, a total of 335 (34.4%) patients died. Compared to surgical patients with no subsequent HF, patients with HFpEF and HFmrEF/HFrEF after surgery showed significantly higher all-cause mortality rates [hazard ratio (HR) 1.80, 95% confidence interval (CI) 1.25-2.57, P = 0.001; and HR 1.86, 95% CI 1.16-2.98, P = 0.010, respectively]. This increased mortality rate was similar to the control HFpEF group without surgery (HR 2.05, 95% CI 1.38-3.02, P < 0.001). Results remained consistent after adjustment for clinical and imaging risk factors and when using the established HFA-PEFF risk score for HFpEF diagnosis. Notably, only 12.5% of HFpEF patients after surgery were diagnosed with HF despite regular follow-up visits by board-certified cardiologists. In contrast, 92.1% of HFmrEF/HFrEF patients after surgery were diagnosed correctly. CONCLUSIONS: Heart failure with preserved ejection fraction following left-sided valve surgery is highly prevalent, associated with unfavourable outcomes, but rarely recognized.