Citations

Abstract Aims Heart failure (HF) with preserved (HFpEF) and mildly reduced (HFmrEF) ejection fraction are prevalent, yet frequently underdiagnosed syndromes associated with high morbidity and mortality, impaired quality of life, and escalating healthcare expenditures. Although guideline-directed medications like SGLT2 inhibitors have been shown to reduce the risk of hospitalization and cardiovascular death, their use remains limited and substantial residual risk persists. This trial aims to evaluate the safety and performance of a novel left-atrium-to-coronary-sinus shunt (Edwards APTURE transcatheter shunt system) in HFpEF and HFmrEF patients. Methods ALT-FLOW II is a prospective multi-centre, randomized, sham-controlled, double-blinded (patient and assessor) trial. Approximately 100 symptomatic HF patients aged ≥18 years with left ventricular ejection fraction >40% and exercise pulmonary capillary wedge pressure (PCWP) ≥25 mm Hg with a PCWP to right atrial pressure gradient ≥8 mm Hg will be randomized 1:1 to the APTURE shunt vs sham control. Key exclusion criteria include severe HF, significant valvular disease, and more than mild right ventricular dysfunction. The primary endpoints are the safety of the APTURE device at 30 days and change in workload-corrected PCWP normalized to bodyweight at 6 months. Secondary endpoints include changes in patient-reported outcomes, and hemodynamic and echocardiographic parameters through 5 years. The trial will also explore the impact of the device on short-term cardiac remodelling and intra-cardiac flow patterns using multi-modality imaging. Conclusions The ALT-FLOW II trial will evaluate the safety and performance of the APTURE system in symptomatic HFpEF and HFmrEF patients with elevated left atrial pressure.

BACKGROUND: The optimal antithrombotic treatment after transcatheter left atrial appendage closure (LAAC) remains to be determined. The objective of this trial was to compare anticoagulation and antiplatelet therapy for preventing device-related thrombosis (DRT) after LAAC. METHODS: This was a prospective multicenter international randomized trial comparing 2 different antithrombotic strategies for preventing DRT after LAAC in patients with nonvalvular atrial fibrillation. Patients were randomized (1:1) to receive direct oral anticoagulants (DOACs) or dual antiplatelet therapy (DAPT; aspirin+clopidogrel) for 60 days. Patients underwent transesophageal echocardiography at 60 days, and the images were analyzed in a central echocardiography laboratory by experienced echocardiographers blinded to the allocated treatment. The primary outcome was DRT as determined by transesophageal echocardiography 60 days after LAAC in patients receiving the allocated treatment at the time of transesophageal echocardiography (per-protocol analysis). The safety outcome included all-cause mortality, stroke, bleeding, or site-reported DRT within 60 days after LAAC in all randomized patients (intention-to-treat analysis). RESULTS: A total of 510 patients (mean age 77±9 years, 35% women) were included between October 2018 and May 2025, and 253 and 257 patients were randomized to the DOAC and DAPT groups, respectively. Of these, 399 patients underwent transesophageal echocardiography and were receiving the allocated treatment at 60 days after LAAC. The primary outcome occurred in 3 patients (1.5%) in the DOAC group compared with 8 patients (4.1%) in the DAPT group (difference, −2.7% [95% CI, −6.0% to 0.6%]; P =0.110). The safety outcome occurred in 52 patients (22.5%) in the DOAC group compared with 82 patients (34.9%) in the DAPT group (difference, −12.4% [95% CI, −20.6% to −4.2%]; P =0.003), and differences were mainly driven by a lower rate of bleeding events in the DOAC group (44 patients [17.4%] versus 64 patients [24.9%]; difference, −7.5% [95% CI, −14.6% to −0.4%]; P =0.038). CONCLUSIONS: The use of DOACs after LAAC failed to reduce DRT compared with DAPT, but it was associated with an improved safety profile. The results of this study should be interpreted with caution because of statistical power issues related to the narrower-than-expected between-group differences and will need confirmation in future larger studies. REGISTRATION: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT03568890.

ABSTRACT Background The assessment of aortic stenosis (AS) severity remains a challenge in some patients, and hemodynamic exercise testing has been proposed as a diagnostic tool in this population. However, the current understanding of exercise hemodynamics in AS is limited. Methods Retrospective review of 34 adults (aged ≥ 18 years) with ≥ moderate AS and preserved left ventricular ejection fraction (LVEF) undergoing exercise invasive hemodynamics (supine cycle protocol) with simultaneous measurement of aortic and left ventricular pressures. Results Age was 77.1 (IQR 68.6; 84.1) years, and 50% were female. LVEF was 62.1 ± 6.6%. All patients were symptomatic. Resting aortic valve area (AVA) was 1.0 ± 0.2 cm 2 and aortic valve (AV) systolic mean gradient 22.0 ± 7.3 mmHg. At peak exercise (40 [IQR 30; 60] W), AV systolic mean gradient (Δ3 [0.6; 7] mmHg, p < 0.001) and AVA (Δ0.2 [0; 0.6] cm 2 , p = 0.002) significantly increased, while stroke volume (SV) did not (Δ6.8 ± 19.4 ml; p = 0.07). Exercise‐induced changes in AV systolic mean gradient were directly related to changes in cardiac output ( r = 0.53, p = 0.003), being inversely related to exercise systemic vascular resistance ( r = −0.60, p = 0.002). Elevated pulmonary artery wedge pressure was present in 41.2% at rest (≥ 15 mmHg) and 69.7% during exercise (≥ 25 mmHg). Conclusions Symptomatic patients with ≥ moderate AS and preserved LVEF experience small increases in AV mean gradient with exercise, and unlike the normal physiological response to exercise, there was no significant increase in SV. In most patients, AVA rose during exercise. Exercise‐induced elevation in filling pressures was highly prevalent.

Background/Objectives: Atrial fibrillation is a frequent comorbidity amongst patients undergoing mitral valve transcatheter edge-to-edge repair (M-TEER) for mitral regurgitation. Left atrial appendage occlusion (LAAO) can be performed to reduce the risk of stroke in patients with atrial fibrillation. Both procedures require large-bore venous access, transseptal puncture, and real-time imaging of the left atrium. However, limited data exist evaluating the safety and feasibility of concomitant M-TEER and LAAO. Methods: We performed a retrospective review of all concomitant M-TEER and LAAO procedures at our institution between May 2019 and September 2024 to evaluate the safety and feasibility of this approach. Results: Concomitant left atrial appendage occlusion was successful in all 15 patients, requiring an additional 15 min (IQR 11–29) of procedural time. No patients died or had a major vascular complication. Routine transesophageal echocardiography performed within 90 days showed no device related thrombus, and no significant peri-device leak in any patients. Conclusions: Concomitant M-TEER and LAAO are feasible but additional prospective studies or randomized trials are needed to evaluate the potential clinical benefit.

Abstract Aims Inter-atrial shunt device therapy has shown mixed results in clinical trials, with clinical ‘non-responders’ typically showing features of more advanced heart failure. We aimed to analyse the haemodynamic and clinical response of a novel left atrial to coronary sinus (LA-CS) shunt device in patients with higher natriuretic peptide (NP) levels, a marker of disease severity. Methods and results An analysis population (n = 95) of patients from the ALT-FLOW early feasibility study with left ventricular ejection fraction &gt;40% and 1-year follow up was analysed. The cohort was divided into low and high subgroups based on NP levels [b-type natriuretic peptide (BNP) and n-terminal pro BNP (NT-proBNP)]. The mean BNP and NT-proBNP levels for low versus high subgroups were 64.2 ± 34.3 versus 261 ± 103 and 322 ± 269 versus 2050 ± 1070 pg/mL, respectively. Patients in the high NP subgroup had evidence of more advanced disease including worse haemodynamic profiles, lower estimated glomerular filtration rate, and higher percentages of atrial fibrillation. The high NP subgroup experienced significant improvements in KCCQ-OSS and NYHA functional class (P &lt; 0.0001 and P &lt; 0.001, respectively) and to a similar magnitude compared with the low NP subgroup. Compared with pre-implant baseline, workload adjusted pulmonary artery wedge pressure at peak exercise declined in the high NP subgroup (PCWL, 164.1 vs. 96.0 mmHg/W/kg at 6 months, P &lt; 0.003) as well as the low NP subgroup (115.9 vs. 65.9 mmHg/W/keg at 6 months, P &lt; 0.001). Importantly, in both NP subgroups, there was preservation of cardiac index through 6 months as well as right ventricular structure (right ventricular diastolic dimension) and function (tricuspid annular systolic plane excursion) through 1 year. Conclusions The quality-of-life, haemodynamic, and functional class improvements along with stable right heart function seen in ALT-FLOW study of LA-CS shunt remain consistent in the subgroup with highest NP levels. This suggests that shunting location could influence outcomes in symptomatic heart failure patients.

Abstract Background Greater vasopressor requirements predict higher mortality in patients with cardiogenic shock (CS).(1) The extent to which CS phenotype modifies the relationship between vasopressor dose and mortality risk is unknown. Purpose We investigated the association between in-hospital mortality and vasopressor dosing (expressed as norepinephrine equivalents [NEE]) during the first 24 hours of hospitalization across distinct CS phenotypes. Methods We included patients with CS admitted to our cardiac intensive care unit (CICU) between 2007 and 2015. Peak combined vasopressor doses during the first 24 hours of hospitalization were recorded as NEE. High dose vasopressor (HDV) use was defined as peak 24 hour NEE &gt;0.3 mcg/kg/min. Unsupervised machine learning was used to assign patients to one of three phenotypes (non-congested, cardiorenal, and haemometabolic), as reported previously by our group and others.(2,3) The primary outcome was in-hospital mortality. Multivariable logistic regression was used to adjust for relevant covariates. Results A total of 1078 patients with CS (median age 69 years, 37% female, 59% with acute myocardial infarction) were admitted to our cardiac intensive care unit (CICU) between 2017 and 2015. The number of patients assigned to each CS phenotype were: haemometabolic (n=325, 30%), cardiorenal (n=314, 29%), non-congested (439, 41%). There was a strong incremental association between in-hospital mortality and NEE (Fig. 1, adjusted OR 1.104 per 0.1 mcg/kg/min, 95% CI 1.134–1.231, P&lt;0.001), and patients receiving HDV (n=234, 22%) had significantly higher in-hospital mortality (57% vs 28%, p&lt;0.001). Among patients who did not receive HDV, mortality was higher in haemometabolic CS (49%) compared to 24% in cardiorenal CS and 21% in non-congested CS (adjusted OR 3.58 relative to non-congested CS, 95% CI 2.46-5.23, p&lt;0.001, Fig. 1). Among patients receiving HDV, hemometabolic CS was also associated with higher mortality (68%) than those with cardiorenal (46.2%) or non-congested CS (39.3%), (adjusted OR 3.26 relative to non-congested CS, 95% CI 1.75-6.18, P&lt;0.001, Fig. 1). Conclusion Integration of CS phenotype with vasopressor requirements may provide incremental prognostic information in CS during the first 24 hours of admission, with haemometabolic CS portending a greater mortality risk even at lower NEE. Patients with HDV (particularly those requiring &gt;=1 mcg/kg/min NEE) had high mortality irrespective of CS phenotype.Figure 1

OBJECTIVES: The objectives of our systematic review and meta-analyses were to determine the diagnostic accuracy of central venous oxygen saturation (Scvo 2) in estimating mixed venous oxygen saturation (Svo 2) and cardiac index in critically ill patients. DATA SOURCES: A systematic search using MEDLINE, Cochrane Central Register of Controlled Trials, and Embase was completed on May 6, 2024. STUDY SELECTION: Studies of patients in the ICU for whom Scvo 2 and at least one reference standard test was performed (thermodilution and/or Svo 2) were included. DATA EXTRACTION: Individual patient data were used to calculate the pooled intraclass correlation coefficient (ICC) for Svo 2 and Spearman correlation for cardiac index. The Quality Assessment of Diagnostic Accuracy Studies-2 and Grading Recommendations Assessment, Development, and Evaluation tools were used for the risk of bias and certainty of evidence assessments. DATA SYNTHESIS: Of 3427 studies, a total of 18 studies with 1971 patients were identified. We meta-analyzed 16 studies (1335 patients) that used Svo 2 as a reference and three studies (166 patients) that used thermodilution as reference. The ICC for reference Svo 2 was 0.83 (95% CI, 0.75–0.89) with a mean difference of 2.98% toward Scvo 2. The Spearman rank correlation for reference cardiac index is 0.47 (95% CI, 0.46–0.48; p < 0.0001). CONCLUSIONS: There is moderate reliability for Scvo 2 in predicting Svo 2 in critical care patients with variability based on sampling site and presence of sepsis. There is limited evidence on the independent use of Scvo 2 in predicting cardiac index.

Abstract Aims Aortic stenosis (AS) is a progressive disease predominantly affecting elderly patients that carries significant morbidity and mortality without aortic valve replacement, the only proven treatment. Our objective was to determine the cost-effectiveness of AS screening using transthoracic echocardiography (TTE) in a geriatric population from the perspective of the publicly funded healthcare system in Canada. Methods and results Markov models estimating the cost-effectiveness ratio (ICER) for AS screening with a one-time TTE were developed. The model included diagnosed and undiagnosed AS health states, hospitalizations, transcatheter aortic valve replacement (TAVR), and post-TAVR health states. Primary analysis included screening at 70 and 80 years of age with intervention at symptom onset, with scenario analysis included for early intervention at the time of severe asymptomatic AS diagnosis. Monte Carlo simulation of 5000 replications was completed with a lifetime horizon and a 1.5% discount for costs and outcomes.Screening for AS at the age of 70 years was associated with an ICER of $156 722, and screening at 80 years of age was associated with an ICER of $28 005, suggesting that screening at 80 years of age is cost-effective when willingness-to-pay per QALY is $50 000. Scenario analysis with early intervention was not cost-effective, with an ICER of $142 157 at 70 years and $124 651 at 80 years. Conclusion Screening for AS at 80 years of age with a one-time TTE, in a Canadian population, improves quality of life and is cost-effective in a publicly funded healthcare system providing, TAVR is reserved for symptomatic patients.