Composite Endpoint Of All-cause Mortality Research Articles

Predicting heart failure symptoms from the apnoea-hypopnoea index determined by full- night polysomnography.

Sleep-disordered breathing (SDB) is closely related to cardiovascular diseases. The higher the apnoea-hypopnoea index (AHI), the higher the prevalence of cardiovascular diseases. Despite these findings suggesting a close link between SDB and heart failure, the relationship between the severity of SDB and the onset of heart failure symptoms in individuals without apparent heart failure symptoms (Heart Failure Stage A+B) remains poorly understood. Between December 2010 and June 2017, we conducted full-night polysomnography (PSG) at the Nippon Medical School Chiba Hokusoh Hospital, extracting patients who were at risk of heart failure (Stage A or B in the Heart Failure Guidelines). Using a median cut-off of AHI≥41.6 events/hour, we divided the patients into two groups and examined the composite endpoint of all-cause mortality plus hospitalization due to heart failure as the primary endpoint. We included 230 patients (mean age 63.0±12.5years, 78.3% males) meeting the selection criteria. When comparing the two groups, those with AHI<41.6 events/hour (L group, n=115) and those with AHI≥41.6 events/hour (H group, n=115), the H group had higher body mass index and higher serum triglyceride, and lower the frequency of acute coronary syndrome and lower estimated glomerular filtration rate than did the L group, but no other patient characteristics differed significantly. The H group had a significantly higher incidence of the composite endpoint than did the L group (10.6% vs. 2.6%, P=0.027). Factors associated with the composite endpoint were identified through multivariate analyses, with AHI, haemoglobin, and left atrial dimension emerging as significant factors (hazard ratio [HR]=1.02, 95% confidence interval [CI]=1.00-1.04, P=0.024; HR=0.71, 95% CI=0.54-0.94, P=0.017; and HR=1.10, 95% CI=1.03-1.18, P=0.006, respectively). Conversely, the minimum SpO2 during PSG (<80%) was not associated with the composite endpoint. In patients with SDB who are at risk of heart failure, severe SDB is associated with a high risk of all-cause mortality and the development of heart failure. Additionally, combining cardiac echocardiography and PSG data may improve risk stratification, offering potential assistance for early intervention. Further examination with a validation cohort is necessary.

Bioactive adrenomedullin as a marker of congestion and disease progression in patients with a systemic right ventricle

BackgroundAdults with a systemic right ventricle (sRV) are at a high risk for heart failure (HF) hospitalization and mortality. Bioactive adrenomedullin (bio-ADM) has been proposed as a marker of congestion and prognosis in patients with cardiovascular disease. We aimed to evaluate the association between bio-ADM and mortality and HF events in sRV patients. MethodsPlasma bio-ADM was measured by a novel immunoassay in plasma of 85 sRV patients. A composite endpoint of all-cause mortality and HF events was used as outcome. HF events were defined as onset or progression of HF signs or symptoms requiring hospitalization, initiation or intensification of therapy. Multivariable Cox regression analyses were performed to evaluate the association between bio-ADM and outcome. ResultsThe mean age of the patients was 37 ± 9 years and 65% were male. Patients with higher plasma bio-ADM concentrations were more often treated with diuretics (p = 0.007), possibly because of signs and/or symptoms of congestion. During a median follow-up of 10.2 years, 33.7% of the patients reached the endpoint. After adjustment for age and N-terminal pro B-type natriuretic peptide (NT-pro BNP), higher bio-ADM levels were associated with a higher risk of the composite endpoint (hazard ratio: 2.09 [95%-confidence interval: 1.15–3.78]). Bio-ADM improved risk prediction when added to NT-proBNP and age (C-statistic improved from 0.748 to 0.776 [p = 0.03]). ConclusionsBio-ADM can be considered as a marker of congestion and independent predictor of death and HF events in adult patients with a sRV. Moreover, in terms of risk prediction, it has added value to NT-proBNP.

His Bundle Pacing: Predicting Mortality and Major Complications in Mid-Term Follow-Up.

Introduction: His bundle pacing (HBP) is suitable for 80% of patients with any indication for permanent pacemaker implantation, with a clinical benefit compared to right ventricular pacing (RVP). Although complications and mortality related to RVP are widely reported in the literature, data on HBP are limited. This study aimed to analyze HBP complications and outcomes in the short-term (up to 30 days) and long-term (up to the following 24 months) follow-up (F/U). Materials and Methods: The study includes 373 patients aged ≥ 18, enrolled from October 2015 to May 2019 in a single-center HBP prospective registry conducted in the Department of Electrocardiology, Upper Silesian Medical Centre of the Medical University of Silesia in Katowice, Poland. Mortality and HBP complications were used as end-points: during hospitalization and up to 30 days (short-term F/U), and for each F/U point-six months, 12 months, and 24 months after the procedure (long-term F/U). Results: Successful HBP was achieved in 252 patients (68%), with an increasing success rate during consecutive years: 57% in 2015-2016 and 73% in 2017-2019. Complications were found in 8.4% of patients (21/252) in short-term F/U and 5.8% (13/224), 5.5% (11/201), and 6.9% (12/174) at six months, 12 months, and 24 months, respectively. There were no deaths during the first 30 days. However, 26 patients (10.3%) died within 24 months. A left ventricular ejection fraction (LVEF) ≤ 34% was the only independent predictor of all-cause mortality or any major complication in the 24-month F/U. Conclusions: This single-center study reported a low risk of mortality and complications associated with HBP at the short-term F/U. However, during the long-term F/U, we observed a higher but acceptable risk of major complications, with a lower LVEF being an independent predictor of the composite end-point of all-cause mortality or any major complication.

The effect of pituitrin on postoperative outcomes in patients with pulmonary hypertension undergoing cardiac surgery: a study protocol for a randomized controlled trial.

The vasoplegic syndrome is one of the major consequences of cardiac surgery. If pulmonary hypertension is additionally involved with vasoplegic syndrome, circulation management becomes much more complicated. According to previous studies, pituitrin (a substitute for vasopressin, which contains vasopressin and oxytocin) not only constricts systemic circulation vessels and increases systemic circulation pressure but also likely decreases pulmonary artery pressure and pulmonary vascular resistance. The aim of this study is to investigate whether pituitrin is beneficial for the postoperative outcomes in patients with pulmonary hypertension undergoing cardiac surgery. The randomized controlled trial will include an intervention group continuously infused with 0.04 U/(kg h) of pituitrin and a control group. Adult patients with pulmonary hypertension undergoing elective cardiac surgery will be included in this study. Patients who meet the conditions and give their consent will be randomly assigned to the intervention group or the control group. The primary outcome is the composite endpoint of all-cause mortality within 30 days after surgery or common complications after cardiac surgery. Secondary outcomes include the incidence of other postoperative complications, length of hospital stay, and so on. Pituitrin constricts systemic circulation vessels, increases systemic circulation pressure, and may reduce pulmonary artery pressure and pulmonary vascular resistance, which makes it a potentially promising vasopressor during the perioperative period in patients with pulmonary hypertension. Therefore, evidence from randomized controlled trials is necessary to elucidate whether pituitrin influences outcomes in patients with pulmonary hypertension following cardiac surgery.

Left ventricular strain-volume loops in bicuspid aortic valve: new insights in hemodynamics and prognostic value

Abstract Background Bicuspid aortic valve (BAV) is a common congenital cardiac disease with a high risk of adverse outcomes. By combining left ventricular (LV) global longitudinal strain (GLS) with LV volume during the cardiac cycle, LV strain-volume loops (SV-loops) can be generated. This may be a valuable biomarker in early detection of LV deterioration. The aim of this study is to describe SV-loop characteristics in BAV patients and investigate its prognostic value. Methods BAV patients were compared with healthy controls, matched for age and sex on a group level. Apical 2, 3 and 4 chamber views were used to measure LV GLS and volume to construct SV-loops. The parameters measured from these SV-loops are depicted in Figure 1A. Associations with the composite endpoint of all-cause mortality, heart failure and supraventricular and ventricular arrhythmias were assessed by univariable Cox regression. Results 113 BAV patients were included (median age 32 years, 40% female). The median aortic jet velocity was 2.3 m/s [IQR 1.6-3.3] and 21 patients (19%) had moderate aortic regurgitation. A clear rightward shift in average SV-loops was seen between BAV patients and healthy controls (figure 1B). Sslope was significantly lower in BAV patients (0.21%/mL, [IQR 0.17-0.28] vs. 0.27%/mL [0.24-0.34], p&amp;lt;0.001), as was ESslope (0.19%/mL [0.12-0.25] vs. 0.29%/mL [0.21-0.43], p&amp;lt;0.001). Moreover, greater uncoupling was seen in BAV patients, both early (0.48±1.29 vs. 0.05±1.21, p=0.018) and late diastolic (0.66±1.02 vs -0.07±1.07, p&amp;lt;0.001). During a median follow-up period of 9.9 years [9.3-10.4], 17 patients experienced a primary endpoint. Echocardiographic parameters associated with the primary endpoint were early diastolic uncoupling (HR 1.82, p=0.009), E/e’ ratio (HR 1.29, p&amp;lt;0.001), ESslope (HR 0.55, p=0.03) and LV end-systolic volume (HR 1.05, p=0.03). Conclusion Significant differences in SV-loop characteristics were observed between BAV patients and healthy controls, suggesting its capability to provide new insights in cardiac hemodynamics and detect LV remodelling at an early stage. Moreover, SV-loops can be promising new prognostic markers.

Insights on Titin cardiomyopathy: from truncating variants site to phenotypic expression and outcomes

Abstract Background Titin truncating variants (TTNtv) represent the most prevalent genotype underlying dilated cardiomyopathy (DCM). Recent molecular studies provided initial evidence about distinct pathogenic mechanisms of different protein truncating sites (A-band vs non-A-band), possibly related to the presence or absence of truncated peptides. Yet, clinical studies on TTNtv-DCM failed to demonstrate any relevant clinical difference according to the band affected. We hypothesized this lack of distinction could be due to the selection bias of including only DCM patients. Thus, we studied the clinical phenotypes and outcomes of our entire population of TTNtv carriers, regardless of phenotypic expression at onset. Methods We retrospectively analysed a population of pathogenic TTNtv carriers, enrolled in our referral centre. TTNtv were classified according to their site (Z disk, I band, A band, A-M junction, M band) and further grouped for analysis in A-band and non-A band. Kaplan-Meier curves were estimated for the primary composite endpoint of all-cause mortality and heart transplant (HTx); while cumulative incidence functions were estimated for the two secondary endpoints (i) heart failure-related death, heart transplantation, or destination left ventricular assist device implantation (LVAD) and (ii) first major ventricular arrhythmia (MVA, defined as sudden death or life-threatening ventricular arrhythmia), compared by Gray’s test. Analyses were then repeated adding an independent cohort of TTVtv carriers from another tertiary centre. Results 161 TTNtv carriers were included in the study (79% A-band, 21% non-A band), 63% were probands. The most prevalent phenotype was DCM (92%). Mean age at diagnosis was 43±16 years and 68% were males. There was no difference between groups in the primary composite outcome nor in the secondary composite endpoint of heart failure-related death, HTx or destination LVAD. Instead, MVA were significantly more frequent in the non-A-band group, in which 45% (n=15) of TTNtv carriers experienced MVA as compared to 17% (n=20) of subjects in the A-band group (p=0.001). Interestingly, we observed a tendency in MVA occurring at a higher mean left ventricular ejection fraction (LVEF) in the non-A-band group as compared to the A-band group (42±13% vs 35±9%, respectively). Furthermore, there was no significant association between MVA and LVEF at the event in the non-A group, while this association was significant in A-band (p=0.03). When an external population of 22 TTNtv carriers (95% DCM, 77% A-band) was added for analysis, this secondary outcome was confirmed (p&amp;lt;0.001). Conclusions Among TTNtv carriers referred to two tertiary centres, those with a mutation in the non-A band seem characterized by higher arrhythmic risk, occurring independently from EF. This novel finding highlights the importance of considering the site of TTN truncating variants to guide the most appropriate clinical management for each patient.Fig 1.Secondary Outcome, arrhythmic risk

Left atrial size predicts long-term outcome after balloon mitral valvuloplasty.

The treatment of choice for severe rheumatic mitral stenosis is balloon mitral valvuloplasty (BMV). Numerous predictors of immediate and long-term procedural success have been described. The aims of this study were to describe our experience with BMV over the last decade and to evaluate predictors of long-term event-free survival. Medical records were retrospectively analyzed of patients who underwent BMV between 2009 and 2021. The primary outcome was a composite endpoint of all-cause mortality, mitral valve replacement (MVR), and repeat BMV. Long-term event-free survival was estimated using Kaplan-Meier curves. Logistic regression was used to create a multivariate model to assess pre-procedural predictors of the primary outcome. A total of 96 patients underwent BMV during the study period. The primary outcome occurred in 36 patients during 12-year follow-up: one (1%) patient underwent re-BMV, 28 (29%) underwent MVR, and eight (8%) died. Overall, event-free survival was 62% at 12 years. On multivariate analysis, pre-procedural left atrial volume index (LAVI) > 80 mL/m2 had a significant independent influence on event-free survival, as did previous mitral valve procedure and systolic pulmonary arterial pressure above 50 mmHg. Despite being a relatively low-volume center, excellent short and long-term results were demonstrated, with event-free survival rates consistent with previous studies from high-volume centers. LAVI independently predicted long-term event-free survival.

Transcatheter aortic valve replacement outcomes in patients with low-flow very low-gradient aortic stenosis.

In patients with severe aortic stenosis (AS), low-flow low-gradient (LG) is a known predictor of worse outcomes. However, very LG may represent a distinct population with further cardiac dysfunction. It is unknown whether this population benefits from transcatheter aortic valve replacement (TAVR). We aimed to describe the patient characteristics and clinical outcomes of low-flow very LG severe AS. This single-centre study included all patients with low-flow severe AS between 2019 and 2021. Patients were divided into groups with very LG [mean pressure gradient (MPG) ≤ 20 mmHg], LG (20 < MPG < 40 mmHg), and high-gradient (HG) (MPG ≥ 40 mmHg). Composite endpoint of all-cause mortality and heart failure rehospitalization was compared. A total of 662 patients [very LG 130 (20%); LG 339 (51%); HG 193 (29%)] were included. Median follow-up was 12 months. Very LG cohort had a higher prevalence of comorbid conditions with lower left ventricular ejection fraction (45% vs. 57% vs. 60%; P < 0.001). There was a graded increase in the risk of composite endpoint in the lower MPG strata (P < 0.001). Among those who underwent TAVR, very LG was an independent predictor of the composite endpoint (adjusted HR 2.42 [1.29-4.55]). While LG and HG cohorts had decreased risk of composite endpoint after TAVR compared with conservative management, very LG was not associated with risk reduction (adjusted HR 0.69 [0.35-1.34]). Low-flow very LG severe AS represents a distinct population with significant comorbidities and worse outcomes. Further studies are needed to evaluate the short- and long-term benefits of TAVR in this population.

Outcomes After Transcatheter Mitral Valve Replacement According to Regurgitation Etiology

BackgroundWhether transcatheter mitral valve replacement (TMVR) devices perform similarly with respect to the underlying mitral regurgitation (MR) etiology remains unknown. The aim of the present analysis was to assess outcomes of TMVR according to the MR underlying etiology among the CHoice of OptImal transCatheter trEatment for Mitral Insufficiency (CHOICE-MI) registry. MethodsOf 746 patients, 229 patients (30.7%) underwent TMVR. The study population was subdivided according to primary, secondary, or mixed MR. Patients with mitral annular calcification were excluded. The primary study endpoint was a composite endpoint of all-cause mortality or hospitalization for heart failure at 1 year. Secondary study endpoints were all-cause and cardiovascular mortality at 1 year, New York Heart Association functional class, and residual MR, both at discharge and 1 year. ResultsThe predominant MR etiology was secondary MR (58.4%), followed by primary MR (28.7%) and mixed MR (12.9%). Technical success and procedural mortality were similar according to MR etiology. Discharge echocardiography revealed residual MR 2+ in 11.3%, 3.7%, and 5.3% of patients with primary, secondary, and mixed MR, respectively (P = .1). MR elimination was similar in all groups up to the 1-year follow-up. There was no difference in terms of primary combined outcome occurrence according to MR etiology. One-year all-cause mortality was reported in 28.8%, 24.2%, and 32.1% of patients with primary, secondary, and mixed MR, respectively (P = .07). ConclusionsIn our study we did not find differences in short-term and 1-year outcomes after TMVR according to MR etiology.

The time-dependent prognostic value of coronary computed tomography angiography in symptomatic patients

Abstract Funding Acknowledgements Type of funding sources: Public grant(s) – National budget only. Main funding source(s): State Research Funding for Turku University Hospital. Background Coronary computed tomography angiography (CCTA) is recommended for diagnostic workup of coronary artery disease (CAD) and is known to provide prognostic information. However, it is unknown whether there is time-dependent variation in the prognostic strength of CCTA. Purpose To study the time-varying prognostic value of CCTA in patients with suspected CAD. Methods From two academic medical centers, we identified symptomatic patients who underwent CCTA for suspected CAD. A composite endpoint of all-cause mortality and myocardial infarction was recorded. The prognostic value of non-obstructive or obstructive (≥50%) CAD was assessed by Cox proportional hazard model. The prognostic power of the model according to the cumulative length of follow-up was evaluated by measuring area under the receiver operating characteristic (ROC) curve (AUC) as a function of follow-up time (time-dependent AUC). Results A total of 2662 patients (age 61 ± 10 years, 45% male) were included, with 247 adverse events (9%) during a median follow-up time of 6.9 years (25th–75th percentile 4.9–8.8 years; maximum 13.3 years). Based on CCTA, 804 (30%) patients had no CAD, 963 (36%) had non-obstructive CAD, and 895 (34%) had obstructive CAD. The presence of non-obstructive CAD (adjusted HR 2.24; p = 0.002) or obstructive CAD (adjusted HR 4.42; p&amp;lt;0.001) were independent predictors of adverse outcome. The predictive power of CCTA findings was relatively stable until 10 years of follow-up time, as demonstrated in the Figure showing time-dependent AUC of the adjusted model (solid line) with 95% confidence intervals (dashed lines). A model including only clinical variables is shown for comparison. Conclusion Coronary CTA findings retain their prognostic value in at least 10-year follow-up of symptomatic patients evaluated for suspected CAD.

#3807 HEART FAILURE IN ASCEND-ND AND ASCEND-D

Abstract Background and Aims Heart failure (HF) is a common cardiovascular (CV) complication in chronic kidney disease (CKD) [1]. Two CV outcome trials (ASCEND-ND [NCT02876835][2] and ASCEND-D [NCT02879305][3]) have provided the principal assessment of CV risk with daprodustat in CKD: both studies showed noninferiority of daprodustat to erythropoiesis-stimulating agent (ESA). Here, we examined the risk of HF in daprodustat-treated patients in the ASCEND-ND and ASCEND-D trials. Method The Phase 3, open-label, randomised, event-driven ASCEND trials investigated oral, once-daily daprodustat vs injectable ESA in patients with anaemia of CKD not on (ASCEND-ND) or on (ASCEND-D) dialysis. Time-to-first adjudicated major adverse CV event (MACE) was the primary CV endpoint. Time-to-first MACE or hospitalisation for heart failure (HHF) was a key secondary endpoint; the composite of time-to-first adjudicated MACE + HHF was assessed as a principal secondary endpoint, and time-to-first HHF alone as an additional secondary endpoint. To better understand HF-specific outcomes, post-hoc analyses accounting for competing risk of death were conducted via the composite endpoint of all-cause mortality (ACM) + HHF – more typically employed to evaluate HF-specific outcomes and to assess “hospitalisation-free survival”. Post-hoc subgroup analyses of patients identified as having a baseline HF history were also conducted. Results Overall, 3872 and 2964 patients were randomised in ASCEND-ND and ASCEND-D, respectively. All key prespecified and post-hoc CV endpoints in ASCEND-ND and ASCEND-D are shown in the Table, and the composite endpoint of ACM + HHF is shown in the Figure. In summary, for components of MACE for daprodustat vs ESA, respectively, ACM events were similar between treatment arms in both studies: ASCEND ND: 11.6% vs 12.2%; ASCEND-D: 14.8% vs 14.6%. For HHF alone in both studies, event rates for daprodustat vs ESA, respectively, were: 7.2% vs 5.9% (hazard ratio [HR] 95% confidence interval [CI] = 1.22 [0.95, 1.56]) in ASCEND ND; and 7.5% vs 6.8% (HR [95% CI] = 1.10 [0.84, 1.45]) in ASCEND-D. In post-hoc analyses using the composite endpoint of ACM + HHF in ASCEND-ND, the event rate for daprodustat was 20.3% (n = 393/1937), and the event rate for ESA was 19.0% (n = 368/1935) (HR [95% CI] = 1.09 [0.94, 1.26]). More HHF events were observed in patients with a history of HF (daprodustat: 20.4% [n = 54/265]; ESA: 13.4% [n = 34/254]). In ASCEND-D, ACM + HHF events were similar for daprodustat (24.4% [n = 363/1487]) and ESA (24.8% [n = 366/1477]; HR [95% CI] = 0.98 [0.85, 1.14]). In this composite endpoint in patients with a history of HF in ASCEND-D, there were also more HHF events in those treated with daprodustat (18% [n = 47/267]) vs ESA (13% [n = 32/254]), but there were fewer deaths with daprodustat (21% [n = 56/267]) than ESA (28% [n = 71/254]). For subgroup analyses of daprodustat vs ESA, the proportion of patients with a history of HF at baseline was greater in ASCEND-D (18.0% vs 17.2%) than ASCEND-ND (13.7% vs 13.1%). Incidence of MACE + HHF was similar between treatment arms in both studies. Conclusion Our findings showed that there was a higher HHF risk in daprodustat-treated patients who had a history of HF compared to ESA-treated patients. While HF risk was similar between treatments in patients on dialysis (ASCEND-D) when combining ACM + HHF in a post-hoc analysis, the risk remained numerically higher for daprodustat vs ESA in patients not on dialysis (ASCEND-ND). The underlying mechanism responsible for these observations and differences is not known, although patients with advanced CKD and comorbid HF who are not on dialysis are recognised to be at underlying risk of HF decompensation.

Performance of non-invasive tests and histology for the prediction of clinical outcomes in patients with non-alcoholic fatty liver disease: an individual participant data meta-analysis

Histologically assessed liver fibrosis stage has prognostic significance in patients with non-alcoholic fatty liver disease (NAFLD) and is accepted as a surrogate endpoint in clinical trials for non-cirrhotic NAFLD. Our aim was to compare the prognostic performance of non-invasive tests with liver histology in patients with NAFLD. This was an individual participant data meta-analysis of the prognostic performance of histologically assessed fibrosis stage (F0-4), liver stiffness measured by vibration-controlled transient elastography (LSM-VCTE), fibrosis-4 index (FIB-4), and NAFLD fibrosis score (NFS) in patients with NAFLD. The literature was searched for a previously published systematic review on the diagnostic accuracy of imaging and simple non-invasive tests and updated to Jan 12, 2022 for this study. Studies were identified through PubMed/MEDLINE, EMBASE, and CENTRAL, and authors were contacted for individual participant data, including outcome data, with a minimum of 12 months of follow-up. The primary outcome was a composite endpoint of all-cause mortality, hepatocellular carcinoma, liver transplantation, or cirrhosis complications (ie, ascites, variceal bleeding, hepatic encephalopathy, or progression to a MELD score ≥15). We calculated aggregated survival curves for trichotomised groups and compared them using stratified log-rank tests (histology: F0-2 vs F3 vs F4; LSM: <10 vs 10 to <20 vs ≥20 kPa; FIB-4: <1·3 vs 1·3 to ≤2·67 vs >2·67; NFS: <-1·455 vs -1·455 to ≤0·676 vs >0·676), calculated areas under the time-dependent receiver operating characteristic curves (tAUC), and performed Cox proportional-hazards regression to adjust for confounding. This study was registered with PROSPERO, CRD42022312226. Of 65 eligible studies, we included data on 2518 patients with biopsy-proven NAFLD from 25 studies (1126 [44·7%] were female, median age was 54 years [IQR 44-63), and 1161 [46·1%] had type 2 diabetes). After a median follow-up of 57 months [IQR 33-91], the composite endpoint was observed in 145 (5·8%) patients. Stratified log-rank tests showed significant differences between the trichotomised patient groups (p<0·0001 for all comparisons). The tAUC at 5 years were 0·72 (95% CI 0·62-0·81) for histology, 0·76 (0·70-0·83) for LSM-VCTE, 0·74 (0·64-0·82) for FIB-4, and 0·70 (0·63-0·80) for NFS. All index tests were significant predictors of the primary outcome after adjustment for confounders in the Cox regression. Simple non-invasive tests performed as well as histologically assessed fibrosis in predicting clinical outcomes in patients with NAFLD and could be considered as alternatives to liver biopsy in some cases. Innovative Medicines Initiative 2.

Predicting clinical outcomes in people with NAFLD: no need for a crystal ball?

A key challenge in the management of non-alcoholic fatty liver disease (NAFLD), one of the most common chronic liver diseases globally, is to identify people at highest risk of progression to advanced liver disease. 1 Younossi ZM Non-alcoholic fatty liver disease—a global public health perspective. J Hepatol. 2019; 70: 531-544 Summary Full Text Full Text PDF PubMed Scopus (1051) Google Scholar Early detection is crucial so that individuals who are at risk can be offered interventions and appropriate care before they develop liver-related complications. The most important predictor of progression to advanced liver disease and mortality in individuals with NAFLD is the extent of liver fibrosis. 2 Dulai PS Singh S Patel J et al. Increased risk of mortality by fibrosis stage in nonalcoholic fatty liver disease: systematic review and meta-analysis. Hepatology. 2017; 65: 1557-1565 Crossref PubMed Scopus (1050) Google Scholar Historically, liver biopsy was the only reliable method to assess liver fibrosis. However, it has a number of limitations (eg, cost, invasiveness, sampling bias, and intra-observer and inter-observer variability) and is not a suitable test for screening or monitoring liver disease progression. In clinical practice, non-invasive tests are increasingly used to provide prognostic information about liver disease severity. 3 Sanyal AJ Castéra L Wai-Sun Wong V Non-invasive assessment of liver fibrosis in NAFLD. Clin Gastroenterol Hepatol. 2023; (published online April 14.)https://doi.org/10.1016/j.cgh.2023.03.042 Summary Full Text Full Text PDF Google Scholar The individual participant data meta-analysis reported by Ferenc E Mózes and colleagues in The Lancet Gastroenterology & Hepatology4 Mózes FE Lee JA Vali Y et al. Performance of non-invasive tests and histology for the prediction of clinical outcomes in patients with non-alcoholic fatty liver disease: an individual participant data meta-analysis. Lancet Gastroenterol Hepatol. 2023; (published online June 5.)https://doi.org/10.1016/S2468-1253(23)00141-3 Google Scholar shows that non-invasive tests can also provide prognostic information about key clinical outcomes. 4 Mózes FE Lee JA Vali Y et al. Performance of non-invasive tests and histology for the prediction of clinical outcomes in patients with non-alcoholic fatty liver disease: an individual participant data meta-analysis. Lancet Gastroenterol Hepatol. 2023; (published online June 5.)https://doi.org/10.1016/S2468-1253(23)00141-3 Google Scholar Their analysis compared the performance of three non-invasive tests and liver biopsy in predicting a composite endpoint of all-cause mortality, hepatocellular carcinoma, liver transplantation, and cirrhosis complications in patients with NAFLD. Non-invasive tests were as good as liver biopsy as predictors of clinical outcomes after adjusting for potential confounders. Performance of non-invasive tests and histology for the prediction of clinical outcomes in patients with non-alcoholic fatty liver disease: an individual participant data meta-analysisSimple non-invasive tests performed as well as histologically assessed fibrosis in predicting clinical outcomes in patients with NAFLD and could be considered as alternatives to liver biopsy in some cases. Full-Text PDF Open Access

Long-term impact of pacemaker implantation after TAVI: a subgroup analysis according to previous intraventricular conduction disturbances

Abstract Funding Acknowledgements Type of funding sources: None. Introduction Transcatheter aortic valve implantation (TAVI) is a worldwide accepted treatment for severe aortic stenosis (AS). Conduction system disturbances, frequently requiring permanent pacemaker (PM) implantation, remain one of the most common procedural complication. Whether the permanent ventricular pacing has a deleterious impact on the prognosis of this population remains unclear. Objectives To assess the long-term impact of permanent PM implantation in clinical outcomes after TAVI. Methods We performed a retrospective analysis of consecutive patients (P) who underwent TAVI between 2009 and 2021 in a single tertiary center.P with a PM implanted before TAVI or with in-hospital mortality were excluded from the analysis. PM implantation post-TAVI was defined as an implant during hospital stay after TAVI or in the first month after discharge. Kaplan Meier survival curves were used to estimate the impact of permanent PM after TAVI, regarding the composite endpoint of all-cause mortality and heart failure (HF) hospitalization during a 4 years follow-up period, and a comparison performed according to the presence or absence of baseline intraventricular conduction disturbances. Results 549 P (82±6.6 years, 56.8% female, left ventricular ejection fraction 53±10%, peak gradient 51±15.6 mmHg, aortic valve area 0.7± 0.2 cm2) were included. At baseline, 108 P (20%) had intraventricular conduction disturbances on ECG (50 P with right bundle branch block [RBBB] and 58 P with left bundle branch block [LBBB]). 127 P (23%) required PM implantation after TAVI. Baseline characteristics were similar between P with and without PM implantation, except for age, gender, previous valvular surgery and RBBB (Table 1). At 48 months follow-up, 35% (n=193) met the composite endpoint, that was similar between both groups (35.8% vs. 34.1%, p=0.731). Kaplan-Meier survival curves revealed no difference in the composite endpoint between the two groups (log-rank p=0.170). Further analysis of subgroups according to the presence or absence of baseline intraventricular conduction disturbances revealed a significant difference among the subgroup of P without previous intraventricular conduction disturbances that underwent PM implantation after TAVI (log rank p=0.02) (Fig 1). This difference in the composite endpoint after PM was not found in the subgroups of P with RBBB (log rank p=0.656) or LBBB (log rank p=0.975) at baseline (Fig 2).* Conclusions Permanent PM implant after TAVI does not have an impact on long-term HF hospitalization and mortality. However, in the specific subgroup of P without previous intraventricular conduction disturbances, PM implantation seems to be associated with worse prognosis.

Pharmacist-Driven Dosing Services and Pharmaceutical Care Increase Probability of Teicoplanin Target Concentration Attainment and Improve Clinical and Economic Outcomes in Non-Critically Ill Patients.

Pharmacist-driven (PD) dosing and monitoring services have been shown to improve the clinical and economic outcomes in patients treated with different antibiotics, other than teicoplanin. This study investigates the impact of PD dosing and monitoring services on the clinical and economic outcomes of non-critically ill patients receiving teicoplanin treatment. A single-center retrospective study was conducted. Patients were divided into the PD group and the non-PD (NPD) group. Primary outcomes included the achievement of target serum concentration, and a composite endpoint of all-cause mortality, intensive care unit (ICU) admission, and sepsis or septic shock development during hospitalization or within 30days of hospital admission. The cost of teicoplanin, overall medication cost, and total cost during hospital stay were also compared. A total of 163 patients from January to December 2019 were included and assessed. Seventy patients were assigned to the PD group and 93 to the NPD group. The PD group had a higher percentage of patients reaching the target trough concentration (54% versus 16%, p < 0.001). Around 26% of the patients in the PD group and 50% of the patients in the NPD group met the composite endpoint during their hospital stay (p = 0.002). The PD group exhibited a significantly lower incidence of sepsis or septic shock, shorter hospital stays, reduced drug costs, and lower total expenses. Our study demonstrates that pharmacist-driven teicoplanin therapy can improve the clinical and economic outcomes for non-critically ill patients. https://www.chictr.org.cn ; identifier, ChiCTR2000033521.

Transfusion trigger after operations in high cardiac risk patients (TOP) trial protocol. Protocol for a multicenter randomized controlled transfusion strategy trial

BackgroundThere is substantial uncertainty regarding the effects of restrictive postoperative transfusion among patients who have underlying cardiovascular disease. The TOP Trial's objective is to compare adverse outcomes between liberal and restrictive transfusion strategies in patients undergoing vascular and general surgery operations, and with a high risk of postoperative cardiac events. MethodsA two-arm, single-blinded, randomized controlled superiority trial will be used across 15 Veterans Affairs hospitals with expected enrollment of 1520 participants. Postoperative transfusions in the liberal arm commence when Hb is <10 g/ dL and continue until Hb is greater than or equal to 10 g/dL. In the restrictive arm, transfusions begin when Hb is <7 g/dL and continue until Hb is greater than or equal to 7 g/dL. Study duration is estimated to be 5 years including a 3-month start-up period and 4 years of recruitment. Each randomized participant will be followed for 90 days after randomization with a mortality assessment at 1 year. ResultsThe primary outcome is a composite endpoint of all-cause mortality, myocardial infarction (MI), coronary revascularization, acute renal failure, or stroke occurring up to 90-days after randomization. Events rates will be compared between restrictive and liberal transfusion groups. ConclusionsThe TOP Trial is uniquely positioned to provide high quality evidence comparing transfusion strategies among patients with high cardiac risk. Results will clarify the effect of postoperative transfusion strategies on adverse outcomes and inform postoperative management algorithms.TRIAL REGISTRATION: http://clinicaltrials.gov identifier: NCT03229941

Association of interventricular activation delay with clinical outcomes in cardiac resynchronization therapy

Pacing at sites of longest interventricular delay has been associated with greater reverse remodeling in cardiac resynchronization therapy (CRT). However, the effects of pacing at such sites on clinical outcomes is less well studied. The purpose of this study was to assess the association between interventricular delay and clinical outcomes in CRT patients implanted with quadripolar left ventricular (LV) leads. RALLY-X4 was a registry study of the Acuity X4 quadripolar LV leads. Interventricular delay was measured during unpaced basal rhythm from the right ventricular (RV) lead to the LV lead electrode (E1 to E4) chosen for CRT pacing. Patients were stratified by median RV-LV delay (80 ms) into short and long delay groups; they also were analyzed by multivariable modeling. The primary composite outcome measure was all-cause mortality and heart failure hospitalization (HFH) at 18 months. A total of 581 patients had complete RV-LV delay data. Mean LV ejection fraction was 27%, and 73% had typical left bundle branch block. Predictors of long RV-LV delay included female sex, left bundle branch block, and QRS duration >150 ms. Survival free of the primary outcome at 18-month follow-up was 87% in the long activation delay group compared with 77% in the shortdelay group (P = .0042). Multivariate analysis showed that RV-LV delay was an independent predictor of survival free of HFH (P = .028). Among CRT patients with quadripolar LV pacing leads, longer baseline interventricular activation delay was significantly associated with the composite endpoint of all-cause mortality and HFH.

Prognostic implications of myocardial perfusion imaging by 82-rubidium positron emission tomography in male and female patients with angina and no perfusion defects.

Myocardial perfusion imaging with 82-rubidium positron emission tomography (82Rb-PET) is increasingly used to assess stable coronary artery disease (CAD). We aimed to evaluate the prognostic value of 82Rb-PET-derived parameters in patients with symptoms suggestive of CAD but no significant reversible or irreversible perfusion defects. Among 3726 consecutive patients suspected of stable CAD who underwent 82Rb-PET between January 2018 and August 2020, 2175 had no regional perfusion defects. Among these patients, we studied the association of 82Rb-PET-derived parameters with a composite endpoint of all-cause mortality, hospitalization for unstable angina pectoris, acute myocardial infarction, heart failure, or ischaemic stroke. During a median follow up of 1.7 years (interquartile range 1.1-2.5 years), there were 148 endpoints. Myocardial blood flow (MBF) reserve (MFR), MBF during stress, left ventricular ejection fraction (LVEF), LVEF-reserve, heart rate reserve, and Ca score were associated with adverse outcomes. In multivariable Cox model adjusted for patient and 82Rb-PET characteristics, MFR < 2 (hazard ratio (HR) 1.75, 95% confidence interval (CI) 1.24-2.48), LVEF (HR 1.38 per 10% decrease, 95% CI 1.24-1.54), and LVEF-reserve (HR 1.19 per 5% decrease, 95% CI 1.07-1.31) were significant predictors of endpoints. Results were consistent in subgroups defined by gender, history of ischaemic heart disease, low LVEF, and atrial fibrillation. MFR, LVEF, and LVEF-reserve derived from 82Rb-PET provide prognostic information on cardiovascular outcomes in patients with no perfusion defects. This may aid in identifying patients at risk and might provide an opportunity for preventive interventions.

Abstract 11461: The Hemodynamic Gain Index is an Independent Predictor of Adverse Outcomes, and Comparable to Peak Oxygen Consumption in Patients With Chronic Heart Failure With Reduced Ejection Fraction

Introduction: The hemodynamic gain index (HGI) is a novel simple parameter calculated from resting and peak systolic BP (SBP) and heart rate (HR) during exercise testing. It is a predictor of mortality in population-based cohorts. However, the prognostic significance of the HGI in chronic HFrEF has not been well studied. Hypothesis: The HGI is independently associated with adverse outcomes, and is comparable to other cardiopulmonary exercise testing (CPET) parameters. Methods: Medical records of 1,067 consecutive HFrEF patients (EF ≤ 40%) undergoing CPET for symptom evaluation from 12/2012 to 9/2020 were reviewed. HGI was calculated using the formula, [(SBP peak x HR peak )-(SBP rest x HR rest )]/(SBP rest x HR rest ). Patients with missing vital signs, hypotensive or bradycardic response to exercise were excluded. Primary outcome was the composite endpoint of all-cause mortality, LVAD implantation, and heart transplantation. Multivariable Cox proportional hazard models were used with subgroup analyses based on median age, sex, BMI of 35 kg/m 2 , respiratory exchange ratio (RER) of 1.05, and beta-blocker use. ROC curves with AUCs were used to compare HGI, peak VO 2 , VE/VCO 2 slope and peak end-tidal pressure of CO 2 (PEtCO 2 ). Results: We included 954 HFrEF patients (mean age was 56.3 ± 12.0 years, 72% men, 17% with BMI ≥ 35 kg/m 2 , 86% on beta-blockers, and 73% with RER &gt; 1.05). During a median follow up time of 946 days, the incidence of the composite outcome was 331 (34.7%). After adjustment for age, sex, BMI, comorbidities, and EF, higher HGI was independently associated with lower risk of the adverse outcomes in the main cohort (hazard ratio per unit increase 0.46, 95%CI 0.35 to 0.59, p &lt; 0.001), and all subgroups, except for patients with BMI ≥ 35 kg/m 2 ( Figure 1A ). The HGI was also comparable to peak VO 2 , and outperformed VE/VCO 2 slope and PEtCO 2 ( Figure 1B ). Conclusions: The HGI is an independent predictor of adverse outcomes, and comparable to peak VO 2 in patients with chronic HFrEF.

Left Ventricular Mass with Delayed Enhancement as a Predictor of Major Events in Patients with Myocarditis with Preserved Ejection Fraction.

Background: Cardiac Magnetic Resonance (CMR) has a key role in subjects presenting with acute myocarditis, independent from left ventricular ejection fraction; it is widely used as a non-invasive imaging test for both diagnostic and prognostic purposes. However, poor data is available about the CMR-derived prognostic parameters of acute myocarditis with preserved ejection fraction (AMpEF). The aim of this study was to investigate the role of CMR in predicting outcomes in patients followed up for AMpEF, using a composite endpoint of all-cause mortality and hospitalization for heart failure (HF). Methods: We retrospectively enrolled 61 patients with diagnosed AMpEF. All patients underwent biohumoral, echocardiographic and CMR evaluation in the acute phase. Myocarditis was confirmed by Lake–Louis criteria assessed on CMR images. Mean follow-up was 4.8 ± 0.6 years during which a composite endpoint of all-cause mortality and hospitalization for HF was investigated. Results: The population was fairly homogeneous regarding baseline clinical features. In particular, no significant differences in age and main cardiovascular risk factors were found between patients with and without events at follow-up. Seven patients met the endpoint. They had significantly higher levels of circulating neutrophils in the acute phase (76 ± 7% vs. 61 ± 11%, p = 0.014) and a higher amount of left ventricular mass with delayed enhancement (DE-LVM, 18 (14–29.5) vs. 12 (8–16) g, p = 0.028). At Cox univariate analysis, DE-LVM was the only significant predictor of endpoint, regardless of the site of inflammation. Conclusions: DE-LVM can predict the composite endpoint of all-cause mortality and hospitalization for HF in a population of patients with AMpEF, representing a new added tool for prognostic stratification.