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.

Performance of the recommended ESC/EASD cardiovascular risk stratification model in comparison to SCORE and NT-proBNP as a single biomarker for risk prediction in type 2 diabetes mellitus.

BACKGROUND: Recently, the European Society of Cardiology (ESC) and European Association for the Society of Diabetes (EASD) introduced a new cardiovascular disease (CVD) risk stratification model to aid further treatment decisions in individuals with diabetes. Our study aimed to investigate the prognostic performance of the ESC/EASD risk model in comparison to the Systematic COronary Risk Evaluation (SCORE) risk model and N-terminal pro-B-type natriuretic peptide (NT-proBNP) in an unselected cohort of type 2 diabetes mellitus (T2DM). METHODS AND RESULTS: A total of 1690 T2DM patients with a 10-year follow up for fatal CVD and all-cause death and a 5-year follow up for CVD and all-cause hospitalizations were analyzed. According to ESC/EASD risk criteria 25 (1.5%) patients were classified as moderate, 252 (14.9%) high, 1125 (66.6%) very high risk and 288 (17.0%) were not classifiable. Both NT-proBNP and SCORE risk model were associated with 10-year CVD and all-cause death and 5-year CVD and all-cause hospitalizations while the ESC/EASD model was only associated with 10-year all-cause death and 5-year all-cause hospitalizations. NT-proBNP and SCORE showed significantly higher C-indices than the ESC/EASD risk model for CVD death [0.80 vs. 0.53, p < 0.001; 0.64 vs. 0.53, p = 0.001] and all-cause death [0.73, 0.66 vs. 0.52, p < 0.001 for both]. The performance of SCORE improved in a subgroup without CVD aged 40-64 years compared to the unselected cohort, while NT-proBNP performance was robust across all groups. CONCLUSION: The new introduced ESC/EASD risk stratification model performed limited compared to SCORE and single NT-proBNP assessment for predicting 10-year CVD and all-cause fatal events in individuals with T2DM.

Secondary mitral regurgitation-Insights from microRNA assessment.

BACKGROUND: While secondary mitral regurgitation (sMR) is associated with adverse outcome in heart failure with reduced ejection fraction (HFrEF), key pathophysiologic mechanisms remain poorly understood and might be elucidated by microRNAs (miRNA/miR), that were recently related to cardiac remodelling. This study sought to assess (i) the differences of miRNA profiles in patients with severe sMR compared to matched disease controls, (ii) the correlation between circulating miRNAs and surrogates of sMR severity as well as (iii) the prognostic implications of miRNA levels in severe sMR. MATERIALS AND METHODS: Sixty-six HFrEF patients were included, of these 44 patients with severe sMR 2:1 matched to HFrEF controls with no/mild sMR. A comprehensive set of miRNAs (miR-21, miR-29a, miR-122, miR-132, miR-133a, miR-let7i) were measured and correlated to echocardiographic sMR severity. RESULTS: miRNA patterns differed distinctly between patients with severe sMR and HFrEF controls (P < .05). Among the panel of assessed miRNAs, miR-133a correlated most strongly with surrogates of sMR severity (r = -0.41, P = .001 with sMR vena contracta width). Interestingly, elevated levels of miR-133 were associated with an increased risk for cardiovascular death and/or HF hospitalizations with and adjusted HR of 1.85 (95% CI 1.24-2.76, P = .003). CONCLUSIONS: This study unveils distinct pathophysiologic maladaptions at a cellular level in patients with severe sMR compared to no/mild sMR by showing significant differences in miRNA profiles and correlations with sMR severity, supporting the concept that sMR drives cardiac remodelling in heart failure. Moreover, the increased risk for adverse outcome in HFrEF patients with severe sMR conveyed by miR-133a might indicate irreversible myocardial damage.

Increased concentrations of bioactive adrenomedullin subsequently to angiotensin-receptor/neprilysin-inhibitor treatment in chronic systolic heart failure.

AIMS: The clinically investigated rationale for neprilysin (NEP)-inhibition by angiotensinreceptor-NEPinhibitor (ARNi) therapy is to induce elevations in endogenous natriuretic peptides. NEP, however, cleaves a broad spectrum of substrates, which partially hold significant implications in heart failure with reduced ejection fraction (HFrEF). The effect of NEP inhibition on these peptides has not been investigated thoroughly. This study explored the response of adrenomedullin (ADM) regulation to the initiation of ARNi. METHODS: Seventy-four patients with stable HFrEF and initiation of ARNi were prospectively enrolled, 67 patients on continuous angiotensin-converting-enzyme inhibitor(ACEi)/angiotensin-receptor blocker (ARB) therapy served as control. Plasma bioactive-ADM (bio-ADM), mid-regional-pro-ADM (MR-proADM), B-typenatriuretic peptide (BNP) and N-terminal-pro-BNP (NT-proBNP) were determined at baseline, short-term, 1-year and 2-year follow up. RESULTS: Following ARNi initiation both bio-ADM and MR-proADM concentrations were significantly increased at early and long-term follow up (bio-ADM [pg/mL]: 26.0 [interquartile range {IQR}: 17.7-37.5] vs. 50.8 [IQR: 36.5-78.1] vs. 54.6 [IQR: 42.0-97.1] vs. 57.4 [IQR: 48.5-161.6]; MR-proADM [nmol/L]: 0.87 [IQR: 0.64-1.12] vs. 1.25 [IQR: 0.93-1.79] vs. 1.42 [IQR: 0.95-1.90] vs. 1.60 [IQR: 1.12-2.46], P < .0001 for all). The ratios bio-ADM/MR-proADM and BNP/NT-proBNP increased during ARNi-therapy proving improved availability of bioactive peptides. The proportional increase of bio-ADM markedly exceeded BNP increase. Patients converted to ARNi showed similar biomarker patterns irrespective of baseline renin-angiotensin system blocker therapy, i.e. ACEi or ARB (P > .05 for all), indicating that activation of the ADM-axis arises particularly from NEPinhibition. CONCLUSION: The significant increase of MR-proADM and bio-ADM together with an elevated bioADM/MR-proADM ratio suggest both enhanced formation and reduced breakdown of bioactive ADM following the initiation of ARNi. Activation of the ADM-axis represents a so far unrecognized effect of ARNi.

Secondary valve regurgitation in patients with heart failure with preserved ejection fraction, heart failure with mid-range ejection fraction, and heart failure with reduced ejection fraction.

Secondary mitral regurgitation and secondary tricuspid regurgitation due to heart failure (HF) remain challenging in almost every aspect: increasing prevalence, poor prognosis, notoriously elusive in diagnosis, and complexity of therapeutic management. Recently, defined HF subgroups according to three ejection fraction (EF) ranges (reduced, mid-range, and preserved) have stimulated a structured understanding of the HF syndrome but the role of secondary valve regurgitation (SVR) across the spectrum of EF remains undefined. This review expands this structured understanding by consolidating the underlying phenotype of myocardial impairment with each type of SVR. Specifically, the current understanding, epidemiological considerations, impact, public health burden, mechanisms, and treatment options of SVR are discussed separately for each lesion across the HF spectrum. Furthermore, this review identifies important gaps in knowledge, future directions for research, and provides potential solutions for diagnosis and treatment. Mastering the challenge of SVR requires a multidisciplinary collaborative effort, both, in clinical practice and scientific approach to optimize patient outcomes.

Phenotyping progression of secondary mitral regurgitation in chronic systolic heart failure.

BACKGROUND: Secondary mitral regurgitation (sMR) drives adverse cardiac remodelling in patients with heart failure with reduced ejection fraction (HFrEF). Progression in severity over time contributes to a transition towards more advanced HF stages. Early identification of patients at risk for sMR progression remains challenging. We therefore sought to assess a broad spectrum of neurohumoral biomarkers in patients with HFrEF to explore their ability to predict progression of sMR. METHODS: A total of 249 HFrEF patients were enrolled. Biomarkers encompassing key neurohumoral pathways in heart failure were sampled at baseline, and sMR progression was assessed over 3 years of follow-up. RESULTS: Of 191 patients with nonsevere sMR at baseline, 18% showed progressive sMR within three years after study enrolment. Progression of sMR was associated with higher levels of MR-proADM (adj.OR 2.25, 95% CI 1.29-3.93; P = .004), MR-proANP (adj.OR 1.84, 95% CI 1.14-3.00; P = .012), copeptin (adj.OR 1.66, 95% CI 1.04-2.67; P = .035) and CT-pro-ET1 (adj.OR 1.68, 95% CI 1.06-2.68; P = .027) but not with NT-proBNP (P = .54). CONCLUSION: Increased plasma levels of neurohumoral cardiac biomarkers are predictors of sMR progression in patients with HFrEF and add easily available incremental prognostic information for risk stratification. Importantly, NT-proBNP was not useful to predict progressive sMR in the present analysis. On the contrary, MR-proANP, primarily produced in the atria, copeptin partly triggered by intra-cardiac and intra-arterial pressures and MR-proADM, a marker of forward failure and peripheral released vasoactive CT-proET1, increase based on a progressive loading burden by sMR and may thus serve as better predictors of sMR progression.

GDF-15 in solid vs non-solid treatment-naïve malignancies.

AIM: GDF-15 is an established cardiovascular risk marker but is equally implicated in tumour biology. Elevated levels of GDF-15 have indeed been observed in distinct tumour entities. This study aimed to explore the relation of GDF-15 to other cardiac biomarkers and the general association of GDF-15 on prognosis in an unselected cohort of treatment-naïve cancer patients. METHODS: We prospectively enrolled 555 consecutive patients at time of diagnosis of malignant disease prior receiving anticancer therapy. Plasma GDF-15 concentrations were determined alongside other cardiac and routine laboratory markers. All-cause mortality was defined as primary endpoint. RESULTS: GDF-15 levels were 338 ng/L (IQR:205-534) for the total cohort, and values were comparable for different tumour entities except breast cancer. Metastatic disease was characterized by higher plasma GDF-15 [435 ng/L (IQR:279-614) vs 266 ng/L (IQR:175-427), P < .001]. GDF-15 correlated positively with inflammatory status reflected by CRP, SAA and IL-6 [r = .31, P < .001, r = .23, P < .001 and r = .14, P = .002] and cardiac biomarkers as NT-proBNP, hsTnT, MR-proADM and CT-proET-1 [r = .46; r = .46; r = .59 and r = .50; P < .001 for all]. GDF-15 was significantly associated with all-cause mortality after multivariate adjustment [adj.HR for ln(GDF-15) 1.78, 95%CI:1.47-2.16, P < .001]. There was a significant interaction between solid and haematological malignancies with loss of association of GDF-15 with outcome in myelodysplastic and myeloproliferative disease. CONCLUSIONS: Elevated plasma GDF-15 is associated with progressing disease severity and poor prognosis in solid tumours of treatment-naïve cancer patients. GDF-15 increase is accompanied by worsening systemic inflammation and a subclinical functional impairment of different organs including the heart. GDF-15 represents a promising target for our pathophysiologic understanding in cardio-oncology linking conditions of both cardiac and neoplastic disease.

Refining the prognostic impact of functional mitral regurgitation in chronic heart failure.

Aims: Significant efforts are currently undertaken to reduce functional mitral regurgitation (FMR) in patients with chronic heart failure in the hope to improve prognosis. We aimed to assess the prognostic impact of FMR in heart failure with reduced ejection fraction (HFrEF) under optimal medical therapy (OMT) and various conditions of HFrEF. We further intended to identify a heart failure phenotype, where FMR is most likely a driving force and not a mere bystander of the disease. Methods and results: We prospectively included 576 consecutive HFrEF patients into our long-term observational study. Functional [i.e. New York Heart Association (NYHA) class], echocardiographic, invasive haemodynamic, and biochemical (i.e. NT-proBNP, MR-proANP, MR-proADM, CT-proET-1, copeptin) measurements were performed at baseline. During a median follow-up of 62 months (interquartile range 52-76), 47% of patients died. Severe FMR was a significant predictor of mortality [hazard ratio (HR) 1.76, 95% confidence interval (CI) 1.34-2.30; P < 0.001], independent of clinical (adjusted HR 1.61, 95% CI 1.22-2.12; P = 0.001), and echocardiographic (adjusted HR 1.46, 95% CI 1.09-1.94; P = 0.01) confounders, OMT (adjusted HR 1.81, 95% CI 1.25-2.63; P = 0.002), and neurohumoral activation (adjusted HR 1.38, 95% CI 1.03-1.84; P = 0.03). Subanalysis revealed that severe FMR was associated with poor outcome in an intermediate-failure phenotype of HFrEF i.e. patients with NYHA class II (adjusted HR 2.17, 95% CI 1.07-4.44; P = 0.03) and III (adjusted HR 1.80, 95% CI 1.17-2.77; P = 0.008), moderately reduced left ventricular function (adjusted HR 2.37, 95% CI 1.36-4.12; P = 0.002), and within the second quartile (871-2360 pg/mL) of NT-proBNP (adjusted HR 2.16, 95% CI 1.22-3.86; P = 0.009). Conclusion: In a patient cohort under OMT, the adverse prognostic impact of FMR is given predominantly in a sub-cohort of a specific intermediate-failure phenotype-well-defined functionally, haemodynamically, biochemically, and morphologically.

CD45 Expression in Mitral Valve Endothelial Cells After Myocardial Infarction.

RATIONALE: Ischemic mitral regurgitation, a complication after myocardial infarction (MI), induces adaptive mitral valve (MV) responses that may be initially beneficial but eventually lead to leaflet fibrosis and MV dysfunction. We sought to examine the MV endothelial response and its potential contribution to ischemic mitral regurgitation. OBJECTIVE: Endothelial, interstitial, and hematopoietic cells in MVs from post-MI sheep were quantified. MV endothelial CD45, found post MI, was analyzed in vitro. METHODS AND RESULTS: Ovine MVs, harvested 6 months after inferior MI, showed CD45, a protein tyrosine phosphatase, colocalized with von Willebrand factor, an endothelial marker. Flow cytometry of MV cells revealed significant increases in CD45+ endothelial cells (VE-cadherin+/CD45+/α-smooth muscle actin [SMA]+ and VE-cadherin+/CD45+/αSMA- cells) and possible fibrocytes (VE-cadherin-/CD45+/αSMA+) in inferior MI compared with sham-operated and normal sheep. CD45+ cells correlated with MV fibrosis and mitral regurgitation severity. VE-cadherin+/CD45+/αSMA+ cells suggested that CD45 may be linked to endothelial-to-mesenchymal transition (EndMT). MV endothelial cells treated with transforming growth factor-ß1 to induce EndMT expressed CD45 and fibrosis markers collagen 1 and 3 and transforming growth factor-ß1 to 3, not observed in transforming growth factor-ß1-treated arterial endothelial cells. A CD45 protein tyrosine phosphatase inhibitor blocked induction of EndMT and fibrosis markers and inhibited EndMT-associated migration of MV endothelial cells. CONCLUSIONS: MV endothelial cells express CD45, both in vivo post MI and in vitro in response to transforming growth factor-ß1. A CD45 phosphatase inhibitor blocked hallmarks of EndMT in MV endothelial cells. These results point to a novel, functional requirement for CD45 phosphatase activity in EndMT. The contribution of CD45+ endothelial cells to MV adaptation and fibrosis post MI warrants investigation.

Tricuspid edge-to-edge repair for tricuspid valve prolapse and flail leaflet: feasibility in comparison to patients with secondary tricuspid regurgitation.

AIMS: Transcatheter tricuspid edge-to-edge repair (T-TEER) has gained widespread use for the treatment of tricuspid regurgitation (TR) in symptomatic patients with high operative risk. Although secondary TR is the most common pathology, some patients exhibit primary or predominantly primary TR. Characterization of patients with these pathologies in the T-TEER context has not been systematically performed. METHODS AND RESULTS: Patients assigned to T-TEER by the interdisciplinary heart team were consecutively recruited in two European centres over 4 years. Echocardiographic images were evaluated to distinguish between primary and secondary causes of TR. Both groups were compared concerning procedural results. A total of 339 patients were recruited, 13% with primary TR and 87% with secondary TR. Patients with primary TR had a smaller right ventricle (basal diameter 45 vs. 49 mm, P = 0.004), a better right ventricular function (fractional area change 45 vs. 41%, P = 0.001), a smaller right (28 vs. 34 cm2, P = 0.021) and left (52 vs. 67 mL/m2, P = 0.038) atrium, and a better left ventricular ejection fraction (60 vs. 52%, P = 0.005). The severity of TR was similar in primary and secondary TR at baseline (TR vena contracta width pre-interventional 13 ± 4 vs. 14 ± 5 mm, P = 0.19), and T-TEER significantly reduced TR in both groups (TR vena contracta width post-interventional 4 ± 3 vs. 5 ± 5 mm, P = 0.10). These findings remained stable after propensity score matching. Complications were similar between both groups. CONCLUSION: T-TEER confers equally safe and effective reduction of TR in patients with primary and secondary TR.

Annular remodelling predicts outcome in isolated severe tricuspid regurgitation: a registry-based echocardiographic analysis.

AIMS: Depending on volume status, secondary tricuspid regurgitation (sTR) has a strong dynamic component. In contrast, associated structural dilatation of the tricuspid annulus and the right heart chambers may be less volume dependent. This study aimed to assess the prognostic value of right heart remodelling in isolated severe sTR (isoTR). METHODS AND RESULTS: A total of 36 000 patients from the longitudinal echocardiographic database of our tertiary centre were screened for severe isoTR [vena contracta (VC) ≥ 7 mm] in the absence of atrial fibrillation (AF), other valve disease, and/or reduced systolic left ventricular function. Echocardiographic examinations were re-read, focusing on right ventricular (RV) parameters and on quantitative and qualitative parameters of isoTR. All-cause mortality was defined as the primary endpoint. Two hundred and sixteen patients fulfilled the inclusion criteria. Severe TR was predominant; only few were classified in the new grades massive [n = 23 (10%)] and torrential TR [n = 4 (2%)]. During a median follow-up of 35 months (20-53), all-cause mortality was 31% (n = 67). Multivariate Cox regression analysis revealed no association of VC, effective regurgitant orifice area, or regurgitant volume with all-cause mortality. However, indexed RV end-diastolic diameter (P < 0.001), indexed right atrial dimensions (P = 0.019), and particularly tricuspid valve (TV) annulus diameter diastole index (P = 0.002) and TV annulus diameter systole index (P = 0.001) were significantly associated with outcome. CONCLUSION: Severe isolated TR in the absence of AF is a rare finding with a grim prognosis. Tricuspid annular diameter dimensions rather than quantitative measures of TR proved to be of significant prognostic value indicating a continuous remodelling leading to a 'point of no return' with a dismal outcome.

Excess renin is attributed to the combination of forward and backward failure in HFrEF.

AIMS: Regulation of the renin-angiotensin system (RAS) in heart failure (HF) with reduced ejection fraction (HFrEF) still raises questions, as a large proportion of patients show normal renin levels despite manifest disease. Experimental venous congestion results in reduced renal perfusion pressure and stimulates renin secretion. We hypothesized that excess renin levels are mainly a result of right ventricular failure as a sequalae of left ventricular dysfunction. The study aimed to link right ventricular function (RVF) with renin levels and to investigate further contributors to excess RAS activation. METHODS AND RESULTS: Three hundred thirty-two chronic HFrEF patients undergoing routine ambulatory care were consecutively enrolled in a prospective, registry-based, observational study. Laboratory parameters, including cardiac-specific markers renin, aldosterone, and N-terminal pro-brain natriuretic peptide (NT-proBNP), echocardiographic examination (n = 247), and right heart catheterization (n = 85), were documented. The relationship between renin and its respective parameters was analysed. Renin concentration was not associated with the New York Heart Association class or NT-proBNP. Systolic blood pressure, systemic vascular resistance, serum sodium, aldosterone, and lactate dehydrogenase were associated with increased renin levels (P < 0.035 for all). Renin levels similarly increased with worsening of RVF parameters such as fractional area change, tricuspid annular plane systolic excursion, tissue Doppler imaging, and inferior vena cava diameter (P < 0.011 for all), but not with pulmonary pressure. Excess renin levels were observed when worsening RVF was combined with reduced renal perfusion {625 µIU/mL [interquartile range (IQR): 182-1761] vs. 67 µIU/mL [IQR: 16-231], P < 0.001}, which was associated with worse survival. CONCLUSIONS: While unrelated to classical indices of HF severity, circulating renin levels increase with the worsening of RVF, especially in the combined presence of forward and backward failure. This might explain normal renin levels in HFrEF patients but also excess renin levels in poor haemodynamic conditions.

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.

Low Bone Mineral Density on Computed Tomography: Association with Poor Survival after Transcatheter Aortic Valve Replacement.

Background: Transcatheter aortic valve replacement (TAVR) has evolved as first-line therapy for severe aortic valve stenosis (AS), with pre-procedural computed tomography (CT) providing critical anatomical information. While primarily used for anatomical planning, TAVR-CT also offers an opportunity to assess low bone mineral density (BMD), a known indicator of frailty. Despite this, the prognostic role of BMD in TAVR patients remains unknown. This study aimed to evaluate BMD on routine TAVR-CT and its impact on long-term survival. Methods: In this retrospective study, 770 consecutive TAVR patients (mean age 80.7 ± 6.7 years, 54.0% males) between November 2015 and March 2022 were included. BMD was measured from a single axial image at the thoracic vertebral level on unenhanced CT scans. Cox regression models assessed the impact of BMD on mortality, and Restricted Cubic Spline models identified potential mortality thresholds. Results: The mean BMD value, as measured on non-contrast CT, was 147.5 ± 5.4 Hounsfield units, demonstrating a noteworthy association with mortality (adjusted hazard ratio per 100 HU decrease: 1.27 [95%CI: 1.01-1.59], p = 0.041). Restricted cubic spline analysis indicated that BMD below 200 HU was linked to a substantial increase in mortality risk. Upon crude Cox regression analysis, every 100 HU decrease was associated with a 32% increase in risk for death (HR 1.32 [95%CI: 1.068-1.65)], p = 0.010). Conclusions: In conclusion, low BMD on TAVR-CT is independently associated with reduced survival, suggesting its potential as a tool for comprehensive frailty assessment and improved risk prediction in TAVR patients.

Cardiac Amyloidosis and Valvular Heart Disease.

Growing interest has accrued in the co-existence of cardiac amyloidosis and valvular heart disease. Amyloid infiltration from either transthyretin (ATTR) or of light chain (AL) origin may affect any structure of the heart, including the valves. The recent literature has mainly focused on aortic stenosis and cardiac amyloidosis, improving our understanding of the epidemiology, diagnosis, treatment and prognosis of this dual pathology. Despite being of high clinical relevance, data on mitral/tricuspid regurgitation and cardiac amyloidosis are rather scarce and mostly limited to case reports and small cases series. It is the aim of this review article to summarize the current evidence of concomitant valvular heart disease and cardiac amyloidosis by including studies on epidemiology, diagnostic approaches, screening possibilities, therapeutic management, and prognostic implications.

Renin Trajectories and Outcome in Stable Heart Failure with Reduced Ejection Fraction (HFrEF) on Contemporary Therapy: A Monocentric Study from an Austrian Tertiary Hospital Outpatient Clinic.

Introduction: The renin-angiotensin system (RAS) is the main target of neurohumoral therapy in heart failure with reduced ejection fraction (HFrEF) effectively reducing mortality. Reasonably, renin might serve as a biomarker for risk prediction and therapy response. Renin indeed bears some additional value to clinical risk models, albeit the effect is not pronounced. Whether assessing renin trajectories can overcome the weaknesses of single renin measurements has not been reported. Methods: A total of 505 patients with stable HFrEF were enrolled prospectively and followed through routine clinical visits. Active plasma renin concentration was documented up to 5 years. Changes in renin were analyzed throughout the disease course, and survival was compared for different renin trajectories within the first year. Results: Baseline renin levels were not related to all-cause mortality (crude HR for an increase of 100 µiE/ml: 1.01 (95% CI: 0.99-1.02), p = 0.414) but associated with unplanned HF hospitalizations (crude HR: 1.01 (95% CI: 1.00-1.02), p = 0.015). Renin increased during the disease course from baseline to 1-year and 2-year FUP (122.7 vs. 185.6 µIU/ml, p = 0.039, and 122.7 vs. 258.5 µIU/ml, p = 0.001). Both survival and unplanned HF hospitalization rates were comparable for different renin trajectories at 1-year FUP (p = 0.546, p = 0.357). Conclusions: Intriguingly, renin is not a good biomarker to indicate prognosis in HF, while renin trajectories over a 1-year period do not have an additional value. Rapid physiologic plasma renin variations, but also opposing effects of angiotensinogen-derived metabolites under presence of RAS blockade, might obscure the predictive ability of renin.

Obesity in heart failure with preserved ejection fraction with and without diabetes: risk factor or innocent bystander?

AIMS: Heart failure with preserved ejection fraction (HFpEF) is a condition that commonly coexists with type 2 diabetes mellitus (T2DM) and obesity. Whether the obesity-related survival benefit generally observed in HFpEF extends to individuals with concomitant T2DM is unclear. This study sought to examine the prognostic role of overweight and obesity in a large cohort of HFpEF with and without T2DM. METHODS AND RESULTS: This large-scale cohort study included patients with HFpEF enrolled between 2010 and 2020. The relationship between body mass index (BMI), T2DM, and survival was assessed. A total of 6744 individuals with HFpEF were included, of which 1702 (25%) had T2DM. Patients with T2DM had higher BMI values (29.4 kg/m2 vs. 27.1 kg/m2, P < 0.001), higher N-terminal pro-brain natriuretic peptide values (864 mg/dL vs. 724 mg/dL, P < 0.001), and a higher prevalence of numerous risk factors/comorbidities than those without T2DM. During a median follow-up time of 47 months (Q1-Q3: 20-80), 2014 (30%) patients died. Patients with T2DM had a higher incidence of fatal events compared with those without T2DM, with a mortality rate of 39.2% and 26.7%, respectively (P < 0.001). In the overall cohort, using the BMI category 22.5-24.9 kg/m2 as the reference group, the unadjusted hazard ratio (HR) for all-cause death was increased in patients with BMI <22.5 kg/m2 [HR: 1.27 (confidence interval 1.09-1.48), P = 0.003] and decreased in BMI categories ≥25 kg/m2. After multivariate adjustment, BMI remained significantly inversely associated with survival in non-T2DM, whereas survival was unaltered at a wide range of BMI in patients with T2DM. CONCLUSION: Among the various phenotypes of HFpEF, the T2DM phenotype is specifically associated with a greater disease burden. Higher BMI is linked to improved survival in HFpEF overall, while this effect neutralises in patients with concomitant T2DM. Advising BMI-based weight targets and weight loss may be pursued with different intensity in the management of HFpEF, particularly in the presence of T2DM.

Individuals with HFpEF and concomitant diabetes show a distinct phenotype particularly associated with a higher disease burden and worse outcome. The obesity paradox observed in individuals with heart failure may not be generalized to HFpEF patients with concomitant diabetes.

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.