BACKGROUND: The purpose of the current study was to investigate the clinical implications of elevated donor-derived cell-free DNA (dd-cfDNA) levels in heart transplantation recipients without evidence of rejection observed on endomyocardial biopsy. METHODS: We retrospectively analyzed dd-cfDNA samples from all consecutive heart transplantation recipients between 2019 and 2023, excluding those with multiorgan transplants. Each sample was paired with an endomyocardial biopsy (0. Elevated dd-cfDNA was defined as ≥0.12%, with a subanalysis using a threshold of 0.20%. Graft dysfunction was defined as an ejection fraction<50%. We excluded dd-cfDNA samples with concurrent histologically positive biopsy results, focusing on those with positive dd-cfDNA and negative biopsy findings. A mixed model Cox regression approach was applied to assess for mortality and graft dysfunction. RESULTS: Of 643 dd-cfDNA samples from 227 patients, 238 samples (37%) from 110 patients showed positive dd-cfDNA results with negative endomyocardial biopsy. The median age was 56 years, with 27% females and 53% White patients. The median time from heart transplantation to sample collection was 5 months (interquartile range, 3–12). Among the positive samples, the median dd-cfDNA level was 0.24% (interquartile range, 0.16%–0.53%) with 63% exceeding 0.20%. A higher prevalence of prior treated antibody-mediated rejection was observed in the dd-cfDNA positive group (15% versus 5%; P =0.002). Patients with elevated dd-cfDNA results ≥ 0.20% demonstrated a near 5-fold increased risk of mortality (hazard ratio, 4.6 [95% CI, 1.6–13.4]; P =0.005) and a 3-fold risk of graft dysfunction (hazard ratio, 3.4 [95% CI, 1.0–11.9]; P =0.054) compared with those with negative dd-cfDNA. CONCLUSIONS: In our cohort, patients with positive dd-cfDNA levels and negative biopsy results had higher rates of adverse outcomes, including graft dysfunction and mortality.

The association between the use of statins, renin–angiotensin system (RAS) inhibitors, and/or β-blockers and long-term mortality in patients with aortic stenosis (AS) who underwent surgical aortic valve replacement (SAVR) is unknown. 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 β-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 β-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 β-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). 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.

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.

Microcirculatory dysfunction (MCD) contributes to systemic hypoperfusion and end-organ damage. Prior studies have shown MCD in heart failure (HF), but comparative data across HF severity and heart replacement therapies remain limited. We aimed to assess MCD across the spectrum of advanced HF. We prospectively enrolled adults with stable chronic HF, cardiogenic shock (CS), HeartMate 3 (HM3) left ventricular assist device support, heart transplant (HT), and healthy controls (HCs), between August 2023 and December 2024. Sublingual microcirculation was assessed using handheld vital microscopy and GlycoCheck software. Primary outcomes were between-group differences in: vessel density; capillary blood volume; perfused boundary region; capillary blood flow; and microvascular health score. A total of 376 patients (120 HF, 81 CS, 43 HM3, and 132 HT) and 44 HC were included. The median age was 62 years and one-third were females. Microvascular density was significantly lower in CS and HT vs HF and left ventricular assist device. Flow was higher in HM3 than CS and HT (P = 0.039). CS and HT had lower capillary blood volume than HF (P < 0.01). Perfused boundary region was highest in HT patients. Microvascular health score was significantly lower in all patient cohorts compared to HC (all P < 0.01), with HT also showing lower scores than HM3 (P < 0.001). MCD is variably expressed across the spectrum of HF and its treatments, with particularly severe impairment in patients resuscitated from CS and postheart transplantation. These results suggest that restoration of macrohemodynamics does not equate to microvascular recovery and underscore the need for further investigation into the mechanisms, prognostic significance, and therapeutic targeting of systemic microvascular health in advanced cardiovascular disease.