Mixed aortic valve disease: association with paravalvular leak and reduced survival after transcatheter aortic valve replacement.

AIMS: Transcatheter aortic valve replacement (TAVR) revolutionized the therapy of severe aortic stenosis (AS) with rising numbers. Mixed aortic valve disease (MAVD) treated by TAVR is gaining more interest, as those patients represent a more complex cohort as compared with isolated AS. However, concerning long-term outcome for this cohort only, limited data are available. The aim of the study is to assess the prevalence of MAVD in TAVR patients, investigate its association with paravalvular regurgitation (PVR), and analyse its impact on long-term mortality after TAVR. METHODS AND RESULTS: We conducted a registry-based cohort study using the Vienna TAVR registry, enrolling patients who underwent TAVR at Medical University of Vienna between January 2007 and May 2020 with available transthoracic echocardiography before and after TAVR (n = 880). Data analysis included PVR incidence and long-term survival outcomes. A total of 647 (73.52%) out of 880 patients had ≥ mild aortic regurgitation next to severe AS. MAVD was associated with PVR compared with isolated AS with an odds ratio of 2.06, 95% confidence interval (CI): 1.51-2.81 (P = <0.001). More than mild PVR after TAVR (n = 168 out of 880: 19.09%) was related to higher mortality compared with the absence of PVR with a hazard ratio (HR) of 1.33, 95% CI: 1.05- 1.67 (P = 0.016). MAVD patients developing ≥ mild PVR after TAVR were also associated with higher mortality compared with the absence of PVR with an HR of 1.30 and 95% CI: 1.04-1.62 (P = 0.022). CONCLUSION: MAVD is prevalent among TAVR patients and presents unique challenges, with increased PVR risk and worse outcomes compared with isolated AS. Long-term survival for MAVD patients, not limited to those developing PVR post-TAVR, is compromised. Earlier intervention before the occurrence of structural myocardial damage or surgical valve replacement might be a potential workaround to improve outcomes.

Amyloid Burden Correlates with Electrocardiographic Findings in Patients with Cardiac Amyloidosis-Insights from Histology and Cardiac Magnetic Resonance Imaging.

Cardiac amyloidosis (CA) is associated with several distinct electrocardiographic (ECG) changes. However, the impact of amyloid depositions on ECG parameters is not well investigated. We therefore aimed to assess the correlation of amyloid burden with ECG and test the prognostic power of ECG findings on outcomes in patients with CA. Consecutive CA patients underwent ECG assessment and cardiac magnetic resonance imaging (CMR), including the quantification of extracellular volume (ECV) with T1 mapping. Moreover, seven patients underwent additional amyloid quantification using immunohistochemistry staining of endomyocardial biopsies. A total of 105 CA patients (wild-type transthyretin: 74.3%, variant transthyretin: 8.6%, light chain: 17.1%) were analyzed for this study. We detected correlations of total QRS voltage with histologically quantified amyloid burden (r = -0.780, p = 0.039) and ECV (r = -0.266, p = 0.006). In patients above the ECV median (43.9%), PR intervals were significantly longer (p = 0.016) and left anterior fascicular blocks were more prevalent (p = 0.025). In our survival analysis, neither Kaplan-Meier curves (p = 0.996) nor Cox regression analysis detected associations of QRS voltage with adverse patient outcomes (hazard ratio: 0.995, p = 0.265). The present study demonstrated that an increased amyloid burden is associated with lower voltages in CA patients. However, baseline ECG findings, including QRS voltage, were not associated with adverse outcomes.

Reduction in 99mTc-DPD myocardial uptake with therapy of ATTR cardiomyopathy.

Aims: Novel ribonucleic acid interference (RNAi) therapeutics such as patisiran and inotersen have been shown to benefit neurologic disease course and quality of life in patients with hereditary transthyretin amyloidosis (ATTRv). We aimed to determine the impact of RNAi therapeutics on myocardial amyloid load using quantitative single photon emission computed tomography/computed tomography (SPECT/CT) imaging in patients with ATTRv-related cardiomyopathy (ATTRv-CM). We furthermore compared them with wild-type ATTR-CM (ATTRwt-CM) patients treated with tafamidis.Methods and results: ATTRv-CM patients underwent [99mTc]-radiolabeled diphosphono-1,2-propanodicarboxylic acid (99mTc-DPD) scintigraphy and quantitative SPECT/CT imaging before and after 12 months (IQR: 11.0-12.0) of treatment with RNAi therapeutics (patisiran: n = 5, inotersen: n = 4). RNAi treatment significantly reduced quantitative myocardial uptake as measured by standardised uptake value (SUV) retention index (baseline: 5.09 g/mL vs. follow-up: 3.19 g/mL, p = .028) in ATTRv-CM patients without significant improvement in cardiac function. Tafamidis treatment resulted in a significant reduction in SUV retention index (4.96 g/mL vs. 3.27 g/mL, p < .001) in ATTRwt-CM patients (historical control cohort: n = 40) at follow-up [9.0 months (IQR: 7.0-10.0)] without beneficial impact on cardiac function.Conclusions: RNAi therapeutics significantly reduce quantitative myocardial uptake in ATTRv-CM patients, comparable to tafamidis treatment in ATTRwt-CM patients, without impact on cardiac function. Serial 99mTc-DPD SPECT/CT imaging may be a valuable tool to quantify and monitor response to disease-specific therapies in both ATTRv-CM and ATTRwt-CM.

Impact of stroke history on procedural cerebrovascular insult probability and long-term outcome after TAVI.

BACKGROUND: In TAVI procedural stroke is one of the most feared complications and for this reason also extensively studied. But there is a lack of data concerning the impact of previous stroke on procedural stroke and on long-term survival. The aim of this registry-based cohort study is to evaluate the prevalence of previous stroke in TAVI patients and its impact on procedural stroke risk as well as long-term outcome. METHODS: We included all patients treated with TAVI between January 2007 and December 2020 and investigated concerning previous stroke in their medical history. Among 958 patients, 55 patients had previous stroke and were included in the present analysis. RESULTS: The salient finding of the present study is that previous stroke is significantly associated with higher all-cause mortality and has established itself as a predictor for poor outcome after TAVI. This is also observed after adjusting for confounders like EuroSCORE II (European system for cardiac operative risk evaluation) and AF (atrial fibrillation) as one of the main underlying diseases for cerebrovascular insult (CVI). However, previous stroke is not associated with higher rates of procedural CVI. CONCLUSION: A history of stroke is significantly associated with higher all-cause mortality and has established itself as a predictor for poor outcome after TAVI without higher rates of procedural stroke.

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.

Myocardial structural and functional changes in cardiac amyloidosis: insights from a prospective observational patient registry.

AIMS: The pathophysiological hallmark of cardiac amyloidosis (CA) is the deposition of amyloid within the myocardium. Consequently, extracellular volume (ECV) of affected patients increases. However, studies on ECV progression over time are lacking. We aimed to investigate the progression of ECV and its prognostic impact in CA patients. METHODS AND RESULTS: Serial cardiac magnetic resonance (CMR) examinations, including ECV quantification, were performed in consecutive CA patients. Between 2012 and 2021, 103 CA patients underwent baseline and follow-up CMR, including ECV quantification. Median ECVs at baseline of the total (n = 103), transthyretin [(ATTR) n = 80], and [light chain (AL) n = 23] CA cohorts were 48.0%, 49.0%, and 42.6%, respectively. During a median period of 12 months, ECV increased significantly in all cohorts [change (Δ) +3.5% interquartile range (IQR): -1.9 to +6.9, P < 0.001; Δ +3.5%, IQR: -2.0 to +6.7, P < 0.001; and Δ +3.5%, IQR: -1.6 to +9.1, P = 0.026]. Separate analyses for treatment-naïve (n = 21) and treated (n = 59) ATTR patients revealed that the median change of ECV from baseline to follow-up was significantly higher among untreated patients (+5.7% vs. +2.3%, P = 0.004). Survival analyses demonstrated that median change of ECV was a predictor of outcome [total: hazard ratio (HR): 1.095, 95% confidence interval (CI): 1.047-1.0145, P < 0.001; ATTR: HR: 1.073, 95% CI: 1.015-1.134, P = 0.013; and AL: HR: 1.131, 95% CI: 1.041-1.228, P = 0.003]. CONCLUSION: The present study supports the use of serial ECV quantification in CA patients, as change of ECV was a predictor of outcome and could provide information in the evaluation of amyloid-specific treatments.

Right Atrial Phasic Function in Heart Failure with Preserved Ejection Fraction: Cardiac Magnetic Resonance Feature Tracking and Outcomes.

BACKGROUND: This study sought to investigate the prognostic impact of right atrial (RA) size and function in patients with heart failure with preserved ejection fraction (HFpEF) in sinus rhythm (SR) and atrial fibrillation (AF). METHODS: Consecutive HFpEF patients were enrolled and indexed RA volumes and emptying fractions (RA-EF) were assessed by cardiac magnetic resonance imaging (CMR). For patients in SR, feature tracking of the RA wall was performed during CMR. In addition, all patients underwent right and left heart catheterization and 6 min walk distance (6MWD) and N-terminal prohormone of brain natriuretic peptide (NT-proBNP) evaluations. We prospectively followed patients and used Cox regression models to determine the association of RA size and function with a composite endpoint of heart failure hospitalization and cardiovascular death. RESULTS: A total of 188 patients (71% female patients, 70 ± 8 years old) were included. Ninety-two patients (49%) were in persistent AF. Eighty-five patients reached the combined endpoint during a follow-up of 69 (42-97) months. After a multivariate cox regression analysis, the impaired RA reservoir strain (HR 0.949; 95% CI [0.909-0.990], p = 0.016), the RA reservoir strain rate (HR 0.991; 95% CI [0.983-0.999], p = 0.028), the RA conduit strain (HR 0.932; 95% CI [0.879-0.988], p = 0.019), and the RA conduit strain rate (HR 0.989; 95% CI [0.881-0.997], p = 0.011) were significantly associated with a worse outcome for patients in SR. In persistent AF, no RA imaging parameter was related to outcome after a multivariate regression analysis. CONCLUSIONS: In HFpEF patients in SR, CMR parameters of impaired RA conduit and reservoir function are associated with dismal cardiovascular outcomes. In persistent AF, RA parameters lose their prognostic ability.

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.

Contemporary insights into the epidemiology, impact and treatment of secondary tricuspid regurgitation across the heart failure spectrum.

AIM: Tricuspid regurgitation secondary to heart failure (HF) is common with considerable impact on survival and hospitalization rates. Currently, insights into epidemiology, impact, and treatment of secondary tricuspid regurgitation (sTR) across the entire HF spectrum are lacking, yet are necessary for healthcare decision-making. METHODS AND RESULTS: This population-based study included data from 13 469 patients with HF and sTR from the Viennese community over a 10-year period. The primary outcome was long-term mortality. Overall, HF with preserved ejection fraction was the most frequent (57%, n = 7733) HF subtype and the burden of comorbidities was high. Severe sTR was present in 1514 patients (11%), most common among patients with HF with reduced ejection fraction (20%, n = 496). Mortality of patients with sTR was higher than expected survival of sex- and age-matched community and independent of HF subtype (moderate sTR: hazard ratio [HR] 6.32, 95% confidence interval [CI] 5.88-6.80, p < 0.001; severe sTR: HR 9.04; 95% CI 8.27-9.87, p < 0.001). In comparison to HF and no/mild sTR patients, mortality increased for moderate sTR (HR 1.58, 95% CI 1.48-1.69, p < 0.001) and for severe sTR (HR 2.19, 95% CI 2.01-2.38, p < 0.001). This effect prevailed after multivariate adjustment and was similar across all HF subtypes. In subgroup analysis, severe sTR mortality risk was more pronounced in younger patients (<70 years). Moderate and severe sTR were rarely treated (3%, n = 147), despite availability of state-of-the-art facilities and universal health care. CONCLUSION: Secondary tricuspid regurgitation is frequent, increasing with age and associated with excess mortality independent of HF subtype. Nevertheless, sTR is rarely treated surgically or percutaneously. With the projected increase in HF prevalence and population ageing, the data suggest a major burden for healthcare systems that needs to be adequately addressed. Low-risk transcatheter treatment options may provide a suitable alternative.

A streamlined, machine learning-derived approach to risk-stratification in heart failure patients with secondary tricuspid regurgitation.

AIMS: Secondary tricuspid regurgitation (sTR) is the most frequent valvular heart disease and has a significant impact on mortality. A high burden of comorbidities often worsens the already dismal prognosis of sTR, while tricuspid interventions remain underused and initiated too late. The aim was to examine the most powerful predictors of all-cause mortality in moderate and severe sTR using machine learning techniques and to provide a streamlined approach to risk-stratification using readily available clinical, echocardiographic and laboratory parameters. METHODS AND RESULTS: This large-scale, long-term observational study included 3359 moderate and 1509 severe sTR patients encompassing the entire heart failure spectrum (preserved, mid-range and reduced ejection fraction). A random survival forest was applied to investigate the most important predictors and group patients according to their number of adverse features.The identified predictors and thresholds, that were associated with significantly worse mortality were lower glomerular filtration rate (<60 mL/min/1.73m2), higher NT-proBNP, increased high sensitivity C-reactive protein, serum albumin < 40 g/L and hemoglobin < 13 g/dL. Additionally, grouping patients according to the number of adverse features yielded important prognostic information, as patients with 4 or 5 adverse features had a fourfold risk increase in moderate sTR [4.81(3.56-6.50) HR 95%CI, P < 0.001] and fivefold risk increase in severe sTR [5.33 (3.28-8.66) HR 95%CI, P < 0.001]. CONCLUSION: This study presents a streamlined, machine learning-derived and internally validated approach to risk-stratification in patients with moderate and severe sTR, that adds important prognostic information to aid clinical-decision-making.

Monitoring of mitral- and tricuspid valve interventions with CardioMEMS: Insights beyond imaging.

BACKGROUND: Mitral- and tricuspid regurgitation are associated with significant morbidity and mortality and are increasingly treated interventionally. CardioMEMS is a transcutaneously implanted pressure sensor placed in the pulmonary artery that allows invasive measurement of pulmonary artery pressure and cardiac output. METHODS: This proof-of-concept study aimed to observe hemodynamic changes as determined by CardioMEMS after transcatheter atrioventricular valve interventions, assess the additional value of CardioMEMS on top of echocardiography, and investigate a potential effect of CardioMEMS on outcome. Patients treated with transcatheter mitral- or tricuspid valve interventions (mitral: TMVR, tricuspid: TTVR) or bicaval valve implantation (bi-CAVI) were recruited. All patients were followed for 12 months. RESULTS: Thirty-six patients were included (4 with CardioMEMS, 32 controls). Patients with CardioMEMS were monitored prior to intervention and 3-12 months thereafter (one received TMVR, one bi-CAVI, one both TMVR and TTVR, and one isolated TTVR). CardioMEMS group: In both patients with TMVR and in the patient with bi-CAVI, mean pulmonary artery pressures decreased (all p < .001) and cardiac output increased significantly (both TMVR p < .001 and bi-CAVI p = .006) while functional parameters, echocardiography, and NT-proBNP were difficult to interpret, unreliable, or both. Changes after TTVR remained inconclusive. CONCLUSION: Invasive monitoring using CardioMEMS provides important information after mitral- and tricuspid valve interventions. Such data pave the way for a deeper understanding of the prerequisites for optimal patient selection and management for catheter-based interventions.

Incidence, causes, correlates, and outcome of bioprosthetic valve dysfunction and failure following transcatheter aortic valve implantation.

AIMS: Bioprosthetic valve dysfunction (BVD) is a major concern regarding transcatheter aortic valve implantation (TAVI) durability. We aimed to assess incidence, correlates, causes, and outcome of early to mid-term BVD after TAVI in relation to patient's life expectancy. METHODS AND RESULTS: Consecutive TAVI recipients (2007-20) with a follow-up ≥1 year were prospectively included. BVD and bioprosthetic valve failure (BVF) were assessed according to Valve-Academic-Research-Consortium-3. BVD/BVF and all-cause death served as endpoints. Average life expectancy was calculated from National Open Health Data and patients were stratified according to tertiles (1st: <6.85 years, 2nd: 6.85-9.7 years, 3rd: >9.7 years). Of 1047 patients (81.6 ± 6.8 years old, EuroSCORE II 4.5 ± 2.5), ≥2 follow ups were available from 622 (serial echo cohort). After a median echo follow up of 12.2 months, incidence rates of BVD/BVF were 8.4% (95% confidence interval 6.7-10.3), and 3.5% (2.5-4.9) per valve-year, respectively, without differences between life expectancy tertiles. The incidence of BVD was two-fold higher within the first year of implant (9.9% per valve-year) vs. beyond (4.8% per valve-year). Valve-in-valve procedure and residual stenosis, but not age/life expectancy predisposed for BVD. BVD/BVF were independently associated with outcome for patients in the first [adjusted hazard ratio (AHR) 1.72 (1.06-2.88)/2.97 (1.72-6.22)] and second [AHR 1.96 (1.02-3.73)/2.31 (1.00-5.30)], but not the third tertile of life expectancy (P = n.s.). CONCLUSIONS: In this large prospective observational cohort, early to mid-term BVD after TAVI occurred at the same rate across the spectrum of life expectancy and was associated with increased mortality in patients with short but not in those with the longest life expectancy.

Hepatic T1-Time Predicts Cardiovascular Risk in All-Comers Referred for Cardiovascular Magnetic Resonance: A Post-Hoc Analysis.

BACKGROUND: Liver damage is frequently observed in patients with cardiovascular disease but infrequently quantified. We hypothesized that in patients with cardiovascular disease undergoing cardiac magnetic resonance, liver T1-times indicate liver damage and are associated with cardiovascular outcome. METHODS: We measured hepatic T1-times, displayed on standard cardiac T1-maps, in an all-comer cardiac magnetic resonance-cohort. At the time of cardiac magnetic resonance, we assessed validated general liver fibrosis scores. Kaplan-Meier estimates and Cox-regression models were used to investigate the association between hepatic T1-times and a composite endpoint of non-fatal myocardial infarction, heart failure hospitalization, and death. RESULTS: One thousand seventy-five participants (58±18 year old, 47% female) were included (972 patients, 50 controls, 53 participants with transient elastography). Hepatic T1-times were 590±89 ms in patients and 574±45 ms in controls (P=0.052). They were significantly correlated with cardiac size and function, presence of atrial fibrillation, NT-pro-BNP levels, and gamma-glutamyl-transferase levels (P<0.001 for all). During follow-up (58±31 months), a total of 280 (29%) events occurred. On Cox-regression, high hepatic T1-times yielded a significantly higher risk for events (adjusted hazard ratio, 1.66 [95% CI, 1.45-1.89] per 100 ms increase; P<0.001), even when adjusted for age, sex, left and right ventricular ejection fraction, NT-proBNP (N-terminal prohormone of brain natriuretic peptide), and myocardial T1-time. On receiver operating characteristic analysis and restricted cubic splines, we found that a hepatic T1-time exceeding 610 ms was associated with excessive risk. CONCLUSIONS: Hepatic T1-times on standard cardiac magnetic resonance scans were significantly associated with cardiac size and function, comorbidities, natriuretic peptides, and independently predicted cardiovascular mortality and morbidity. A hepatic T1-time >610 ms seems to indicate excessive risk. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT04220450.

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.

Reverse Remodeling Following Valve Replacement in Coexisting Aortic Stenosis and Transthyretin Cardiac Amyloidosis.

BACKGROUND: Dual pathology of severe aortic stenosis (AS) and transthyretin cardiac amyloidosis (ATTR) is increasingly recognized. Evolution of symptoms, biomarkers, and myocardial mechanics in AS-ATTR following valve replacement is unknown. We aimed to characterize reverse remodeling in AS-ATTR and compared with lone AS. METHODS: Consecutive patients referred for transcatheter aortic valve replacement (TAVR) underwent ATTR screening by blinded 99mTc-DPD bone scintigraphy (Perugini Grade-0 negative, 1-3 increasingly positive) before intervention. ATTR was diagnosed by DPD and absence of monoclonal protein. Reverse remodeling was assessed by comprehensive evaluation before TAVR and at 1 year. RESULTS: One hundred twenty patients (81.8±6.3 years, 51.7% male, 95 lone AS, 25 AS-ATTR) with complete follow-up were studied. At 12 months (interquartile range, 7-17) after TAVR, both groups experienced significant symptomatic improvement by New York Heart Association functional class (both P<0.001). Yet, AS-ATTR remained more symptomatic (New York Heart Association ≥III: 36.0% versus 13.8; P=0.01) with higher residual NT-proBNP (N-terminal pro-brain natriuretic peptide) levels (P<0.001). Remodeling by echocardiography showed left ventricular mass regression only for lone AS (P=0.002) but not AS-ATTR (P=0.5). Global longitudinal strains improved similarly in both groups. Conversely, improvement of regional longitudinal strain showed a base-to-apex gradient in AS-ATTR, whereas all but apical segments improved in lone AS. This led to the development of an apical sparing pattern in AS-ATTR only after TAVR. CONCLUSIONS: Patterns of reverse remodeling differ from lone AS to AS-ATTR, with both groups experiencing symptomatic improvement by TAVR. After AS treatment, AS-ATTR transfers into a lone ATTR cardiomyopathy phenotype.

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.

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.

Comparison of Hepatic Tissue Characterization between T1-Mapping and Non-Contrast Computed Tomography.

Background: Non-contrast computed tomography (CT) is frequently used to assess non-alcoholic/metabolic fatty liver disease (NAFLD/MAFLD), which is associated with cardiovascular risk. Although liver biopsy is considered the gold standard for diagnosis, standardized scores and non-contrast computed tomography (CT) are used instead. On standard cardiac T1-maps on cardiovascular imaging (CMR) exams for myocardial tissue characterization hepatic tissue is also visible. We hypothesized that there is a significant correlation between hepatic tissue T1-times on CMR and Hounsfield units (HU) on non-contrast CT. Methods: We retrospectively identified patients undergoing a non-contrast CT including the abdomen, a CMR including T1-mapping, and laboratory assessment within 30 days. Patients with storage diseases were excluded. Results: We identified 271 patients (62 ± 15 y/o, 49% female) undergoing non-contrast CT and CMR T1-mapping within 30 days. Mean hepatic HU values were 54 ± 11 on CT and native T1-times were 598 ± 102 ms on CMR and there was a weak, but significant, correlation between these parameters (r = −0.136, p = 0.025). On age and sex adjusted regression analysis, lower liver HU values indicated a dismal cardiometabolic risk profile, including higher HbA1C (p = 0.005) and higher body mass index (p < 0.001). In contrast, native hepatic T1-times yielded a more pronounced cardiac risk profile, including impaired systolic function (p = 0.045) and higher NT-proBNP values (N-Terminal Brain Natriuretic Peptide) (p = 0.004). Conclusions: Hepatic T1-times are easy to assess on standard T1-maps on CMR but only weakly correlated with hepatic HU values on CT and clinical NAFLD/MAFLD scores. Liver T1-times, however, are linked to impaired systolic function and higher natriuretic peptide levels. The prognostic value and clinical usefulness of hepatic T1-times in CMR cohorts warrants further research.

Comprehensive myocardial characterization using cardiac magnetic resonance associates with outcomes in low gradient severe aortic stenosis.

AIMS: This study sought to compare cardiac magnetic resonance (CMR) characteristics according to different flow/gradient patterns of aortic stenosis (AS) and to evaluate their prognostic value in patients with low-gradient AS. METHODS AND RESULTS: This international prospective multicentric study included 147 patients with low-gradient moderate to severe AS who underwent comprehensive CMR evaluation of left ventricular global longitudinal strain (LVGLS), extracellular volume fraction (ECV), and late gadolinium enhancement (LGE). All patients were classified as followings: classical low-flow low-gradient (LFLG) [mean gradient (MG) < 40 mmHg and left ventricular ejection fraction (LVEF) < 50%]; paradoxical LFLG [MG < 40 mmHg, LVEF ≥ 50%, and stroke volume index (SVi) < 35 ml/m2]; and normal-flow low-gradient (MG < 40 mmHg, LVEF ≥ 50%, and SVi ≥ 35 ml/m2). Patients with classical LFLG (n = 90) had more LV adverse remodelling including higher ECV, and higher LGE and volume, and worst LVGLS. Over a median follow-up of 2 years, 43 deaths and 48 composite outcomes of death or heart failure hospitalizations occurred. Risks of adverse events increased per tertile of LVGLS: hazard ratio (HR) = 1.50 [95% CI, 1.02-2.20]; P = 0.04 for mortality; HR = 1.45 [1.01-2.09]; P < 0.05 for composite outcome; per tertile of ECV, HR = 1.63 [1.07-2.49]; P = 0.02 for mortality; HR = 1.54 [1.02-2.33]; P = 0.04 for composite outcome. LGE presence also associated with higher mortality, HR = 2.27 [1.01-5.11]; P < 0.05 and composite outcome, HR = 3.00 [1.16-7.73]; P = 0.02. The risk of mortality and the composite outcome increased in proportion to the number of impaired components (i.e. LVGLS, ECV, and LGE) with multivariate adjustment. CONCLUSIONS: In this international prospective multicentric study of low-gradient AS, comprehensive CMR assessment provides independent prognostic value that is cumulative and incremental to clinical and echocardiographic characteristics.