Composite Endpoint Of All-cause Mortality Research Articles

Transthyretin stabiliser therapy in patients with transthyretin amyloid cardiomyopathy: a systematic review and meta-analysis

Abstract Introduction The safety and efficacy of transthyretin (TTR) stabilisers in patients with transthyretin amyloid cardiomyopathy (ATTR-CM) remains unclear. Objectives We aimed to assess whether TTR stabilisers are effective and safe to promote medical optimisation in patients with ATTR-CM. Methods We systematically searched PubMed, Embase and Cochrane for studies comparing the use of TTR stabilisers with placebo or no TTR stabilisers in patients with ATTR-CM. Statistical analyses were performed using RevMan 5.1.7. Heterogeneity was examined with the Cochran Q test and I2 statistics. Risk ratios (RR) and hazard ratios (HR) with 95% confidence intervals (CI) were computed with a random-effects model for binary endpoints. Results We included 2 randomised controlled trials (RCT) and 12 observational studies, comprising 3324 patients, of whom 1563 (47,02%) received TTR stabilisers. Follow-up ranged from 7 to 36 months. TTR stabilisers were significantly associated with lower all-cause mortality (RR 0.32; 95% CI 0.18-0.57; p<0.01) and cardiovascular hospitalisation (RR 0.67; 95% CI 0.52-0.86; p=0.02) as compared with control group. In a sub analysis of RCTs and multivariate-adjusted data, the composite endpoint of all-cause mortality, heart transplant, and cardiac assist device implantation yielded significant lower rates in the TTR stabiliser group (HR 0.46; 95% CI 0.28-0.73; p=0.01). Conclusion In patients with ATTR-CM, TTR stabilisers were associated with significant lower rates of all-cause mortality and cardiovascular hospitalisations as compared with control group.

Comparative outcomes of drug-coated balloon angioplasty versus second-generation drug-eluting stent for in-stent restenosis: a real-world data analysis

Abstract Background Coronary in-stent restenosis (ISR) poses a significant challenge in interventional cardiology, with optimal treatment strategies being the subject of ongoing debate. Current clinical guidelines offer a choice between drug-coated balloon angioplasty (DCB) and repeat stenting with second-generation drug-eluting stents (DES), each with distinct implications for long-term patient outcomes. Purpose The aim of this study is to compare 1-year outcomes between DCB angioplasty and second-generation DES in the treatment of ISR. Longitudinal real-world data are used from the OBSERVABLE database, which comprises German health claims data between 2012 and 2021. Methods A total of 10,440 ISR individuals undergoing DCB or DES intervention were identified. After exclusion of bare-metal stents, first generation stents and non-DCBs, 3,810 propensity score-matched individuals remained. The primary outcome was the composite of all-cause mortality and myocardial infraction (MI). Secondary outcomes included all-cause death, MI, and bleeding as a safety outcome. Results At 1-year follow-up, the primary outcome of all-cause mortality and MI was observed in 246 individuals (12.9%) in the DES group, compared with 201 individuals (10.6%) in the DCB group (HR, 1.27; 95% CI, 1.06-1.53). Sensitivity analysis confirmed the robustness of these findings. Secondary outcomes revealed higher all-cause mortality in the DES group (7.9%) compared to the DCB group (6.3%) (HR, 1.31; 95% CI, 1.03-1.66), with no difference in MI. Bleeding events were comparable between the two treatments, with 244 individuals (12.8%) in the DES group and 206 individuals (10.8%) in the DCB group (HR, 1.17; 95% CI, 0.89-1.53). Conclusion This real-world data analysis demonstrated a higher incidence of the primary composite endpoint of all-cause mortality and MI within one year, after treatment with DES compared to DCB. Our results support prior findings about the safety profile of repeated DES implantation and strengthen DCB as a potential superior alternative to DES in ISR management.

Multiple comorbidities are associated with poor prognosis in patients with ADHF-HFpEF and non-frailty or mild frailty but not moderate-severe frailty -PURSUIT-HFpEF Registry-

Abstract Background A variety of comorbidities are frequently observed and represent a major problem in the management of patients with heart failure. Frailty is a strong predictor of poor clinical outcome in patients with heart failure, which may be partially attributable to the presence of multiple comorbidities. However, it remains to be clarified whether frailty is prognostically useful in relation to multiple comorbidities in patients with acute decompensated heart failure and preserved ejection fraction (ADHF-HFpEF). Purpose The purpose of this study is to investigate the relationship between frailty, multiple comorbidities and prognosis in patients with ADHF-HFpEF. Methods We prospectively studied 1028 patients with ADHF-HFpEF. Frailty was assessed using Clinical Frailty Scale (CFS). Multiple comorbidities were defined as the presence of 4 or more factors from the following 11 groups: diabetes, obesity, lung disease, anemia, renal dysfunction, electrolyte disorder, dyslipidemia, depression, hypertension, stroke and cancer. The primary outcome of this study was the composite endpoint of all-cause mortality and rehospitalization for worsening heart failure. Results During a mean follow-up period of 1.6±1.3 years, 454 patients underwent primary outcome. CFS (p<0.001) and the number of comorbidities (p=0.006) were significantly independently associated with primary outcome after multivariate adjustment. Kaplan-Meier analysis revealed that patients with multiple comorbidities had significantly higher risk for primary outcome than those without multiple comorbidities in the group with non-frailty (defined as CFS of 1 or 2, p=0.019) and mild frailty (CFS of 3 or 4, p=0.036). However, there was no significant difference in the group with moderate or greater frailty (CFS of 5 or more) in patients with ADHF-HFpEF. Conclusion(s) Multiple comorbidities would be associated with poor prognosis in patients with ADHF-HFpEF and non-frailty or mild frailty but not in patients with moderate or greater frailty.Multiple comorbidities and MACE risk

Conduction system versus right ventricular pacing for atrioventricular block: a reconstructed individual participant data meta-analysis

Abstract Background Right ventricular pacing (RVP) is typically offered to patients with established or impending atrioventricular block (AVB) in the absence of left ventricular systolic dysfunction. Direct stimulation of His-Purkinje fibres via conduction system pacing (CSP) is an emerging alternative to RVP to prevent pacing-induced cardiomyopathy. Purpose To perform a systematic review and meta-analysis testing CSP versus RVP in patients with AVB and a left ventricular ejection fraction ≥35%. Methods Observational studies comparing CSP with RVP that reported clinical outcomes were systematically identified. The primary outcome was time-to-first all-cause mortality, heart failure hospitalisation (HFH) or upgrade to biventricular pacing. Secondary endpoints included the individual components of the primary endpoint. Individual participant time-to-event data (IPD) was obtained through data-sharing agreements or reconstructed from digitisation of Kaplan-Meier curves where available. Mixed-effects Cox proportional hazards regression that modelled between-study heterogeneity as a random intercept to account for differing baseline hazards between distinct study populations was performed on these data. Conventional pairwise random effects meta-analyses were also performed. This analysis was prospectively registered. Results 12 eligible studies enrolling 4627 patients were included. In reconstructed IPD pooled survival analyses, CSP associated with a 38% reduced hazard of the primary endpoint compared with RVP [hazard ratio 0.62, 95% CI 0.51 to 0.76, p<0.001] (Figure 1). In pairwise meta-analyses, CSP associated with a 46% risk reduction in the primary endpoint [relative risk (RR) 0.54, 95% CI 0.41 to 0.71, p<0.001] (Figure 2A). CSP also associated with reductions in risk of all-cause mortality [RR 0.60, 95% CI 0.45 to 0.80, p<0.001], HFH [RR 0.39, 95% CI 0.28 to 0.55, p<0.001] and upgrade to biventricular pacing [RR 0.19, 95% CI 0.07 to 0.52, p=0.001] compared with RVP (Figure 2B-D). Conclusions In reconstructed IPD pooled survival analyses, CSP associated with reductions in the primary composite endpoint of all-cause mortality, heart failure hospitalisation or upgrade to biventricular pacing compared with RVP, independent of ventricular pacing burden. This was mirrored in conventional meta-analyses of the primary composite endpoint, and when individual components of the composite were analysed. It may not be necessary to predict which patients will have an elevated pacing burden when applying this therapy. Until randomised data from the PROTECT-HF trial becomes available, this analysis offers the most precise summary estimate of the comparative effects of CSP versus RVP in patients with an AVB indication for pacing, but no evidence of heart failure.Kaplan-Meier plot comparing CSP vs RVPForest plots for major endpoints

Leukocyte Indices as Markers of Inflammation and Predictors of Outcome in Heart Failure with Preserved Ejection Fraction.

Background: The pathophysiology of heart failure (HF) with preserved ejection fraction (HFpEF) is suggested to be influenced by inflammation. Leukocyte indices, including the neutrophil-lymphocyte ratio (NLR), the monocyte-lymphocyte ratio (MLR), and the pan-immune inflammation value (PIV), can be utilized as biomarkers of systemic inflammation. Their prognostic utility is yet to be fully understood. Methods: Between December 2010 and May 2023, patients presenting to a tertiary referral center for HFpEF were included into a prospective registry. The association of the NLR, MLR, and PIV with the composite endpoint of all-cause mortality and HF-related hospitalization was tested utilizing Cox regression analysis. Results: In total, 479 patients (median 74.3, interquartile range (IQR): 69.22-78.3 years, 27.8% male) were included. Patients were observed for 43 (IQR: 11-70) months, during which a total of 267 (55.7%) patients met the primary endpoint. In a univariate Cox regression analysis, an above-the-median NLR implied a hazard ratio (HR) of 1.76 (95%-confidence interval (CI): 1.38-2.24, p < 0.001), an MLR of 1.46 (95%-CI: 1.14-1.86, p = 0.003), and a PIV of 1.67, 95%-CI: 1.30-2.13, p < 0.001) for the composite endpoint. After adjustment in a step-wise model, the NLR (HR: 1.81, 95%-CI: 1.22-2.69, p = 0.003), the MLR (HR: 1.57, 95%-CI: 1.06-2.34, p = 0.026), and the PIV (HR: 1.64, 95%-CI: 1.10-2.46, p = 0.015) remained significantly associated with the combined endpoint. Conclusions: The NLR, the MLR, and the PIV are simple biomarkers independently associated with outcomes in patients with HFpEF.

Heart failure with preserved ejection fraction and atrial fibrillation: catheter ablation vs. standard medical therapy - a systematic review and meta-analysis.

The latest guidelines advocate for catheter ablation (CA) over standard medical therapy (SMT) for managing atrial fibrillation (AF) in patients with heart failure with reduced ejection fraction (HFrEF). However, significant knowledge gaps exist regarding the effectiveness of CA vs. SMT in patients with heart failure with preserved ejection fraction (HFpEF). PubMed, Scopus, and Embase until February 2024 were systematically searched. Given the limited number of randomized studies, propensity score-matched observational studies comparing CA with SMT in AF patients with HFpEF were also included. The primary outcome was a composite endpoint of all-cause mortality and HF hospitalization. Eight studies that enrolled 17,717 SMT and 2537 CA patients were included. CA was associated with a significantly lower risk of the composite endpoint of all-cause mortality and HF hospitalization (HR 0.61; 95% CI, 0.43-0.85). The risk of HF hospitalization (HR 0.44; 95% CI, 0.23-0.83), cardiovascular mortality (HR 0.43; 95% CI, 0.22-0.84), and AF recurrence (HR 0.53; 95% CI, 0.39-0.73) were also lower in the CA group. CA demonstrated significant cardiovascular morbidity and mortality benefits compared to SMT in the HFpEF population.

Perioperative outcome of left atrial appendage amputation in coronary artery bypass grafting.

Left atrial appendage (LAA) amputation performed alongside cardiac surgery has become an increasingly established procedure to reduce stroke risk in patients with atrial fibrillation. As the recommendation levels for LAA amputation continue to rise, ample evidence assessing its perioperative safety and risk factors is of utmost interest. All patients who underwent isolated coronary artery bypass grafting (CABG) between 2018 and 2021 at two high-volume centers were retrospectively included in the study. Patients were divided into two groups-the CABG and CABG + LAA groups-based on whether they underwent concomitant LAA amputation. Propensity score matching (PS matching) was applied to ensure comparability between the groups. The primary endpoint was defined as a composite outcome comprising of all-cause mortality, stroke, and reoperation. Secondary endpoints included the components of the primary endpoint, perioperative outcome parameters, transfusion rates, and laboratory parameters. A total of 3904 patients were included with 3038 and 866 in the CABG and CABG + LAA group, respectively. After PS matching each group consisted of 856 patients. The primary endpoint showed no significant differences between the CABG and CABG + LAA group (7.0% vs. 6.5% (OR 0.9 95% CI [0.64; 1.35], p = 0.70)). Similarly, there were no notable differences in the individual components of the composite endpoint: all-cause mortality (p = 0.84), stroke (p = 0.74), and reoperation (p = 0.50). Subgroup results did not show any relevant dissimilarity. The concomitant performance of LAA amputation is not associated with worse in-hospital outcomes, as measured by the composite endpoint of all-cause mortality, stroke, and reoperation.

Diagnosing Myocardial Injury in an Acute Chest Pain Cohort; Long-Term Prognostic Implications of Cardiac Troponin T and I.

There are limited data regarding the utility of follow-up cardiac troponin (cTn) measurements after admission for acute chest pain and how long-term stability of myocardial injury and prognostic value differ when using cardiac troponin T (cTnT) or I (cTnI). We measured high-sensitivity (hs)-cTnT (Roche Diagnostics) and hs-cTnI (Siemens Healthineers) during hospitalization for acute chest pain and after 3 months. Acute myocardial injury was defined as concentrations > sex-specific upper reference limit (URL) during hospitalization and ≤URL at 3-months. Chronic myocardial injury (CMI) was defined as concentrations > URL at both time points. Patients were followed from the 3-month sampling point for a median of 1586 (IQR 1161-1786) days for a primary composite endpoint of all-cause mortality, myocardial infarction (MI), revascularization, and heart failure, and a secondary endpoint of all-cause mortality. Among 754 patients, 33.8% (hs-cTnT) and 19.2% (hs-cTnI) had myocardial injury during hospitalization. The rate of CMI was 5 times higher by hs-cTnT (20%) assay than hs-cTnI (4%), while acute myocardial injury was equally common; 14% (hs-cTnT) and 15% (hs-cTnI), respectively (6% and 5% when excluding index non-ST-elevation MI (NSTEMI). For hs-cTnT, peak index concentration, 3-month concentration and classification of CMI predicted the primary endpoint; hazard ratios (HRs) 1.38 (95% CI 1.20-1.58), 2.34 (1.70-3.20), and 2.31 (1.30-4.12), respectively. For hs-cTnI, peak index concentration predicted the primary endpoint; HR 1.14 (1.03-1.25). This association was nonsignificant after excluding index NSTEMI. Acute myocardial injury is equally frequent, whereas CMI is more prevalent using hs-cTnT assay than hs-cTnI. Measuring hs-cTnT 3 months after an acute chest pain episode could assist in further long-term risk assessment. ClinicalTrials.gov Registration Number: NCT02620202.

One-Month Duration Compared with Twelve-Month Duration of Dual Antiplatelet Therapy in Elective Angioplasty for Coronary Artery Disease: Bleeding and Ischaemic Outcomes.

Background/Objectives: The need to determine the safest duration of dual antiplatelet therapy duration after elective angioplasty to reduce bleeding events without an adverse effect on major adverse cardiovascular events (MACE) remains a challenge. Methods: In this investigator-initiated, single-centre cohort study, we identified all patients who underwent PCI for de novo coronary disease for stable angina between January 2015 and November 2019. We compared 1-month and 12-month durations of dual antiplatelet therapy (DAPT) to determine if there was any difference in the primary outcome of major bleeding. The secondary outcome was a patient-oriented composite endpoint of all-cause mortality; any myocardial infarction, stroke, or revascularisation; and the individual components of this composite endpoint. Data were analysed using Cox regression models and cumulative hazard plots. Results: A total of 1025 patients were analysed, of which 340 received 1 month of DAPT and 685 received 12 months of DAPT. There was no difference in major bleeding between the two groups (2.6% vs. 2.5% respectively). On univariable cox regression analysis, no characteristics were predictors of major bleeding. A proportion of 99.7% of patients in the 1-month DAPT arm were treated with a DCB strategy, whilst 93% in the 12-month DAPT group were treated with a DES. There was no difference between the two groups with regards to the composite patient-oriented MACE (11% vs. 12%, respectively) or any individual component of this. These results were unchanged after propensity score matched analysis. Conclusions: A 1-month duration of DAPT, for which 99.7% of patients were treated with a DCB strategy, appears safe and effective when compared with a 12-month duration of DAPT with no difference in major bleeding or MACE.

Prognostic value of the electrocardiogram in patients with bicuspid aortic valve disease

BackgroundIdentifying bicuspid aortic valve (BAV) patients at risk for cardiac events remains challenging and the role of the electrocardiogram (ECG) has not yet been described. Therefore, this study aims to describe ECG parameters in BAV patients, and investigate their prognostic value. MethodsIn this single-center prospective study patients with BAV without a prior aortic valve replacement (AVR) were included. Transthoracic echocardiogram and 12‑lead resting-ECG were obtained. Associations between ECG parameters and the composite endpoint of all-cause mortality and AVR were assessed using Cox-proportional hazard analysis. Results120 patients with BAV were included (median age 30 years, 61% male). Median aortic jet velocity was 2.4 m/s [IQR: 1.7–3.4] and 5 patients (4%) had severe aortic regurgitation. All patients were in sinus rhythm. Any ECG abnormality was present in 57 patients (48%). Median PR-interval was 156 [IQR: 138–170] msec. A deviating QRS axis was found in 17 patients (14%) and Cornell criteria for LVH were fulfilled in 20 patients (17%). Repolarization abnormalities were present in 12 patients (10%). Median follow-up duration was 7.0 [6.3–9.8] years, during which 23 patients underwent AVR and 2 patients died. After adjusting for age, a longer PR-interval was associated with worse intervention-free survival (HR 1.02, 95% CI: 1.01–1.04). ConclusionAlmost half of the patients with BAV had abnormalities on their ECG. Moreover, the PR-interval may be an interesting prognostic marker for intervention-free survival in BAV patients.

Perioperative transfusion study (PETS): Does a liberal transfusion protocol improve outcome in high-risk cardiovascular patients undergoing non-cardiac surgery? A randomised controlled pilot study.

Small studies have shown that patients with advanced coronary artery disease might benefit from a more liberal blood transfusion strategy. The goal of this pilot study was to test the feasibility of a blood transfusion intervention in a group of vascular surgery patients who have elevated cardiac troponins in rest. We conducted a single-centre, randomised controlled pilot study. Patients with a preoperative elevated high-sensitive troponin T undergoing non-cardiac vascular surgery were randomised between a liberal transfusion regime (haemoglobin >10.4 g/dL) and a restrictive transfusion regime (haemoglobin 8.0-9.6 g/dL) during the first 3 days after surgery. The primary outcome was defined as a composite endpoint of all-cause mortality, myocardial infarction or unscheduled coronary revascularization. In total 499 patients were screened; 92 were included and 50 patients were randomised. Postoperative haemoglobin was different between the intervention and control group; 10.6 versus 9.8, 10.4 versus 9.4, 10.9 versus 9.4 g/dL on day one, two and three respectively (p < 0.05). The primary outcome occurred in four patients (16%) in the liberal transfusion group and in two patients (8%) in control group. This pilot study shows that the studied transfusion protocol was able to create a clinically significant difference in perioperative haemoglobin levels. Randomisation was possible in 10% of the screened patients. A large definitive trial should be possible to provide evidence whether a liberal transfusion strategy could decrease the incidence of postoperative myocardial infarction in high risk surgical patients.

Prognosis and treatment strategies for atrial fibrillation in heart failure with mildly reduced ejection fraction.

The study investigates the prognosis of atrial fibrillation (AF) in patients with heart failure with mildly reduced ejection fraction (HFmrEF). Data concerning the prognostic impact of AF in patients with HFmrEF is scarce. Consecutive patients with HFmrEF [i.e. left ventricular ejection fraction 41-49% and signs and/or symptoms of heart failure (HF)] were retrospectively included at one institution from 2016 to 2022. Patients with AF were compared with patients without with regard to the primary composite endpoint of all-cause mortality and HF-related rehospitalization at 30 months (median follow-up). Statistical analyses included Kaplan-Meier, multivariable Cox proportional regression analyses, and propensity score matching. A total of 2148 patients with HFmrEF were included with an overall prevalence of AF of 43%. The presence of AF was associated with a higher risk of the primary composite endpoint all-cause mortality and HF-related rehospitalization at 30 months [hazard ratio (HR) = 2.068; 95% confidence interval (CI) 1.802-2.375; P = 0.01], which was confirmed after propensity score matching (HR = 1.494; 95% CI 1.216-1.835; P = 0.01). AF was an independent predictor of both all-cause mortality (HR = 1.340; 95% CI 1.066-1.685; P = 0.01) and HF-related rehospitalization (HR = 2.061; 95% CI 1.538-2.696; P = 0.01). Finally, rhythm control may be associated with lower risk of all-cause mortality compared with rate control for AF (HR = 0.342; 95% CI 0.199-0.587; P = 0.01). Atrial fibrillation affects 43% of patients with HFmrEF and represents an independent predictor of adverse long-term prognosis.

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.

Left Atrial Improvement in Patients With Secondary Mitral Regurgitation and Heart Failure: The COAPT Trial

BackgroundFunctional mitral regurgitation induces adverse effects on the left ventricle and the left atrium. Left atrial (LA) dilatation and reduced LA strain are associated with poor outcomes in heart failure (HF). Transcatheter edge-to-edge repair (TEER) of the mitral valve reduces heart failure hospitalization (HFH) and all-cause death in selected HF patients. ObjectivesThe aim of this study was to evaluate the impact of LA strain improvement 6 months after TEER on the outcomes of patients enrolled in the COAPT (Cardiovascular Outcomes Assessment of the MitraClip Percutaneous Therapy for Heart Failure Patients With Functional Mitral Regurgitation) trial. MethodsThe difference in LA strain between baseline and the 6-month follow-up was calculated. Patients with at least a 15% improvement in LA strain were labeled as “LA strain improvers.” All-cause death and HFH were assessed between the 6- and 24-month follow-up. ResultsAmong 347 patients (mean age 71 ± 12 years, 63% male), 106 (30.5%) showed improvement of LA strain at the 6-month follow-up (64 [60.4%] from the TEER + guideline-directed medical therapy [GDMT] group and 42 [39.6%] from the GDMT alone group). An improvement in LA strain was significantly associated with a reduction in the composite of death or HFH between the 6-month and 24-month follow-up, with a similar risk reduction in both treatment arms (Pinteraction = 0.27). In multivariable analyses, LA strain improvement remained independently associated with a lower risk of the primary composite endpoint both as a continuous variable (adjusted HR: 0.94 [95% CI: 0.89-1.00]; P = 0.03) and as a dichotomous variable (adjusted HR: 0.49 [95% CI: 0.27-0.89]; P = 0.02). The best outcomes were observed in patients treated with TEER in whom LA strain improved. ConclusionsIn symptomatic HF patients with severe mitral regurgitation, improved LA strain at the 6-month follow-up is associated with subsequently lower rates of the composite endpoint of all-cause mortality or HFH, both after TEER and GDMT alone. (Cardiovascular Outcomes Assessment of the MitraClip Percutaneous Therapy for Heart Failure Patients With Functional Mitral Regurgitation [COAPT]; NCT01626079)

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.

Impact of pulmonary vein isolation on the prognosis of patients with atrial fibrillation and heart failure with reduced ejection fraction: an updated systematic review and meta-analysis

Aim. The study aimed to conduct a systematic review and meta-analysis of randomized clinical trials (RCTs) to determine the effect of pulmonary vein isolation (PVI) on the prognosis of patients with atrial fibrillation (AF) and chronic heart failure with reduced ejection fraction (HFrEF).Material and methods. We searched PubMed (MEDLINE), Google Scholar, and the Cochrane Library databases for studies that compared PVI with a conservative rhythm/heart rate (HR) control strategy in patients with AF and HFrEF. The primary endpoint in the major RCTs examining the effect of PVI on the prognosis of patients with HFrEF was a composite endpoint of all-cause mortality or HF-related hospitalization. Hazard ratios (HRs) based on Cox regression analysis were used as the baseline survival rates for the meta-analysis. To determine the weighted mean differences in improvement in left ventricular ejection fraction (LVEF) in the PVI and non-PVI groups, a pooled analysis of the mean LVEF changes with standard deviations taking into account the number of subjects in the compared groups was performed.Results. For this systematic review, 11 studies were selected from 2216 publications, which included 2379 patients. Three RCTs (n=968) were subjected to meta-analysis on time-to-event outcomes. The average follow-up period was 34 months. According to the meta-analysis, PVI was associated with a significant reduction in the risk of composite endpoint (HR: 0,53; 95% confidence interval (CI): 0,33-0,85; p=0,009). In addition, PVI compared with drug rhythm/rate control was associated with a significant reduction in the all-cause mortality risk (HR: 0,55; 95% CI: 0,34-0,89; p=0,01). Finally, a meta-analysis of 10 RCTs (n=1516) found a significant improvement in LVEF compared with drug rhythm/HR control or atrioventricular node ablation with biventricular pacing. The weighted mean difference in the LVEF change over time after 6-12-month follow-up was 5,25% (95% CI: 4,03-6,47; p&lt;0,001).Conclusion. PVI in patients with AF and HFrEF compared with drug rhythm/HR control is associated with a significant reduction in the risk of all-cause mortality and HF-related hospitalization and a greater improvement in LVEF compared with baseline.

I prefer the MitraClip in these cases: the 5-year COAPT data.

The COAPT 5-year data demonstrate that compared with medical treatment transcatheter edge-to-edge repair (TEER) with the MitraClip in symptomatic patients with Grade 3+/Grade 4+ secondary mitral regurgitation (SMR) reduced by nearly half the annualized hospitalization risk (33 vs. 57%), by almost 30% the death rate (57 vs. 67%) and achieved significant and durable SMR reduction in 95% of patients. Control patients who crossed over to TEER at 2 years had better prognosis, but nearly half of them died before reaching crossover eligibility. Death or hospitalization for heart failure (HHF) occurred in 73.6% of TEER patients and 91.5% of controls within 5 years, pointing to a need for further study to address left ventricle (LV) dysfunction, the underlying cause of patient's disease. MTRA-FR targeted SMR using the same device and did not improve the composite endpoint of all-cause mortality or HHF at 12 months. Possible reasons for the discrepancy include enrolment of patients with more severe MR and less-advanced LV disease (dilation/dysfunction), less-procedural complications, and higher success in reducing MR in COAPT compared with MITRA-FR. Thus, the ideal patient for MitraClip treatment would be one with severe MR, but with no too severe LV dilation/dysfunction, which is what differentiates COAPT patients from those in MITRA-FR.

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.