Clinical Utility of the Molecular Microscope Diagnostic System in a Real-World Transplant Cohort: Moving Towards a New Paradigm.

Objectives: To evaluate the clinical implications of adjunctive molecular gene expression analysis (MMDx ) of biopsy specimens in heart transplant (HT ) recipients with suspected rejection. Introduction: Histopathological evaluation remains the standard method for rejection diagnosis in HT. However, the wide interobserver variability combined with a relatively common incidence of "biopsy-negative" rejection has raised concerns about the likelihood of false-negative results. MMDx, which uses gene expression to detect early signs of rejection, is a promising test to further refine the assessment of HT rejection. Methods: Single-center prospective study of 418 consecutive for-cause endomyocardial biopsies performed between November 2022 and May 2024. Each biopsy was graded based on histology and assessed for rejection patterns using MMDx. MMDx results were deemed positive if borderline or definitive rejection was present. The impact of MMDx results on clinical management was evaluated. Primary outcomes were 1-year survival and graft dysfunction following MMDx-guided clinical management. Secondary outcomes included changes in donor-specific antibodies, MMDx gene transcripts, and donor-derived cell-free DNA (dd-cfDNA) levels. Results: We analyzed 418 molecular samples from 237 unique patients. Histology identified rejection in 32 cases (7.7%), while MMDx identified rejection in 95 cases (22.7%). Notably, in 79 of the 95 cases where MMDx identified rejection, histology results were negative, with the majority of these cases being antibody-mediated rejection (62.1%). Samples with rejection on MMDx were more likely to show a combined elevation of dd-cfDNA and peripheral blood gene expression profiling than those with borderline or negative MMDx results (36.7% vs 28.0% vs 10.3%; p<0.001). MMDx results led to the implementation of specific antirejection protocols or changes in immunosuppression in 20.4% of cases, and in 73.4% of cases where histology was negative and MMDx showed rejection. 1-year survival was better in the positive MMDx group where clinical management was guided by MMDx results (87.0% vs 78.6%; log rank p=0.0017). Conclusions: In our cohort, MMDx results more frequently indicated rejection than histology, often leading to the initiation of antirejection treatment. Intervention guided by positive MMDx results was associated with improved outcomes.

Associations between medical therapy after surgical aortic valve replacement for aortic stenosis and long-term mortality: a report from the SWEDEHEART registry.

AIMS: The association between the use of statins, renin-angiotensin system (RAS) inhibitors, and/or ß-blockers and long-term mortality in patients with aortic stenosis (AS) who underwent surgical aortic valve replacement (SAVR) is unknown. METHODS AND RESULTS: All patients with AS who underwent isolated first-time SAVR in Sweden from 2006 to 2017 and survived 6 months after discharge were included. Individual patient data from four mandatory nationwide registries were merged. Cox proportional hazards models, with time-updated data on medication status and adjusted for age, sex, comorbidities, type of prosthesis, and year of surgery, were used to investigate associations between dispensed statins, RAS inhibitors, and ß-blockers and all-cause mortality. In total, 9553 patients were included, and the median follow-up time was 4.9 years (range 0-11); 1738 patients (18.2%) died during follow-up. Statins were dispensed to 49.1% and 49.0% of the patients within 6 months of discharge from the hospital and after 10 years, respectively. Corresponding figures were 51.4% and 53.9% for RAS inhibitors and 79.3% and 60.7% for ß-blockers. Ongoing treatment was associated with lower mortality risk for statins {adjusted hazard ratio (aHR) 0.67 [95% confidence interval (95% CI) 0.60-0.74]; P < 0.001} and RAS inhibitors [aHR 0.84 (0.76-0.93); P < 0.001] but not for ß-blockers [aHR 1.17 (1.05-1.30); P = 0.004]. The associations were robust in subgroups based on age, sex, and comorbidities (P for interactions >0.05). CONCLUSIONS: The results of this large population-based real-world study support the use of statins and RAS inhibitors for patients who underwent SAVR due to AS.

Minimizing the risk for left ventricular rupture during transcatheter aortic valve implantation by reducing the presence of stiff guidewires in the ventricle.

OBJECTIVES: The presence of a stiff guidewire in the apex of the left ventricle (LV) is a known risk factor for LV perforation. Our goal was to minimize the risk of LV rupture during transcatheter aortic valve implantation (TAVI) by omitting the interaction between the stiff guidewire and the LV apex using a modified procedure. METHODS: A TAVI protocol designed to allow minimal interaction between a stiff guidewire and the LV was developed in Linköping University Hospital in Sweden. A total of 316 patients were treated exclusively by this approach between March 2014 and May 2018. RESULTS: All procedures were completed successfully. There were no cases (0%) of ventricular perforation. Only 1 patient (0.3%) had a pericardial effusion, and it was due to annulus rupture. There was 1 case of acute kidney injury (0.3%). Five patients (1.6%) required a new permanent pacemaker. Stroke occurred in 3 patients (0.9%). No patient had valve embolization. Vascular complications were experienced by 6 patients (1.9%). A mild paravalvular leak occurred in 27 (8.5%) patients. At 30 days post-TAVI, 6 patients (2%) had died. The mortality rate at 1 year was 8.6% (n = 20/232). CONCLUSIONS: Our series shows that TAVI without the prolonged use of a stiff guidewire in the LV apex is feasible. The risk of LV perforation is eliminated by this approach, and other procedural complications are limited.