Impact of gender in patients with device-related thrombosis after left atrial appendage closure - A sub-analysis from the multicenter EUROC-DRT-registry.

BACKGROUND: Device-related thrombosis (DRT) is a common finding after left atrial appendage closure (LAAC) and is associated with worse outcomes. As women are underrepresented in clinical studies, further understanding of sex differences in DRT patients is warranted. METHODS AND RESULTS: This sub-analysis from the EUROC-DRT-registry compromises 176 patients with diagnosis of DRT after LAAC. Women, who accounted for 34.7% (61/176) of patients, were older (78.0 ± 6.7 vs. 74.9 ± 9.1 years, p = .06) with lower rates of comorbidities. While DRT was detected significantly later in women (173 ± 267 vs. 127 ± 192 days, p = .01), anticoagulation therapy was escalated similarly, mainly with initiation of novel oral anticoagulant (NOAC), vitamin K antagonist (VKA) or heparin. DRT resolution was achieved in 67.5% (27/40) of women and in 75.0% (54/72) of men (p = .40). In the remaining cases, an intensification/switch of anticoagulation was conducted in 50.% (9/18) of men and in 41.7% (5/12) of women. Final resolution was achieved in 72.5% (29/40) cases in women, and in 81.9% (59/72) cases in men (p = .24). Women were followed-up for a similar time as men (779 ± 520 vs. 908 ± 687 days, p = .51). Kaplan-Meier analysis revealed no difference in mortality rates in women (Hazard Ratio [HR]: 1.73, 95%-Confidence interval [95%-CI]: .68-4.37, p = .25) and no differences in stroke (HR: .83, 95%-CI: .30-2.32, p = .72) within 2 years after LAAC. CONCLUSION: Evaluation of risk factors and outcome revealed no differences between men and women, with DRT in women being diagnosed significantly later. Women should be monitored closely to assess for DRT formation/resolution. Treatment strategies appear to be equally effective.

Ten-year retrospective cohort analysis of ventricular assist device infections.

BACKGROUND: The number of patients treated by ventricular assist devices (VAD) and the duration of VAD treatment is increasing. One of the main complications in terms of morbidity and mortality for VAD patients are microbial infections. With this study, we aimed to investigate the epidemiology and microbiological characteristics of infections occurring in a VAD population to identify modifiable factors. METHODS: We retrospectively analyzed patient characteristics, treatments and outcomes of VAD-specific/related infections. All patients implanted in our institution with a continuous flow VAD between January 2009 and January 2019 were included. Risk factors for VAD infection were assessed using simple and multiple linear regressions. RESULTS: Of the 104 patients screened, 99 were included in the analysis, the majority of which were men (78%). At implantation, the mean age was 56 years and the median time on VAD support was 541 days. The overall infection rate per year per patient was 1.4. Forty-seven patients (60%) suffered from VAD-specific/related infection. Half of all infection episodes occurred in the first 4 months but the proportion of VAD-specific/related infection was higher after the first 4 months (74% of all infection). Using regression models, no patient specific risk factors were associated with VAD-specific/related infections. CONCLUSION: No predictive factors for infection during VAD support were identified in this study. By extension, diabetes, renal insufficiency, age or high BMI are not sufficient to deny a patient access to ventricular support.

Importance of electromagnetic interactions between ICD and VAD devices-Mechanistic assessment.

BACKGROUND: Implanted cardioverter defibrillators (ICDs) and left ventricular assist devices (LVADs) are established interventions that prolong life in advanced heart failure, but their combination has not been demonstrated as beneficial. Electromagnetic interference (EMI) produced by a LVAD can preclude ICD interrogation with external programmers. We undertook a systematic evaluation of the LVAD-ICD interaction "in-vitro" to clarify the extent of this interaction. METHODS: Using explanted ICDs and VADs in a mock physiological rig, we assessed interrogation and reprogramming of ICD devices in the presence of a running LVAD. When connectivity between the ICD programmer and the ICD failed, we attempted three different techniques to re-establish connectivity: (1) Electromagnetic shielding of the ICD with a pseudo-faraday cage; (2) altering the LVAD speed; and (3) increasing the distance between the VAD and the ICD. RESULTS: We tested a total of 24 ICDs from different manufacturers in the presence of the Heartware (HW) and HeartMate 3 (HM3) LVADs. With HW, we only observed interaction with Biotronik ICD devices at very close range (0-6 cm). With HM3, only Medtronic ICD devices showed no interaction. Interactions could be mitigated by increasing the VAD-ICD distance. CONCLUSIONS: LVADs, notably the HM3, produce EMI that interferes with the communication between an ICD and its respective programmer. This may need to be considered when choosing the type of VAD to implant in patients with a previously implanted left-sided ICD. The only safe way to regain connectivity is to increase the distance between the VAD and the ICD, with patients raising their arm above their head.

Impact of individual stroke risk on outcome after Amplatzer left atrial appendage closure in patients with atrial fibrillation.

OBJECTIVES: To investigate periprocedural and long-term outcome of left atrial appendage closure (LAAC) using Amplatzer occluders with respect to individual pre-procedural stroke risk. BACKGROUND: LAAC is a proven strategy for prevention from stroke and bleeding in patients with nonvalvular atrial fibrillation not amenable to oral anticoagulation. Whether individual pre-procedural stroke risk may affect procedural and long-term clinical outcome after LAAC is unclear. METHODS: Multicenter study of consecutive patients who underwent Amplatzer-LAAC. Using pre-procedural CHADS2 score, outcomes were compared between a low (0-2 points) and a high stroke risk group (3-6 points). RESULTS: Five hundred consecutive patients (73.9 ± 10.1 years) who underwent Amplatzer-LAAC. Two hundred and forty eight had preprocedural CHADS2 score ≤ 2 points (low-risk group) and the remaining 252 patients had 3-6 points (high-risk group). Periprocedural complication rates (6.0% vs. 5.6%, p = .85), procedural success (LAAC without major periprocedural or device-related complications or major para-device leaks: 89.4% vs. 87.9%, p = .74), and 30-day-mortality (2.4% vs. 2.6%, p = .77) were comparable. After 1,346 patient-years (PY), the long-term composite efficacy endpoint (stroke, systemic embolism, cardiovascular, and unexplained death) was reached in 23/653 (3.5/100 PY) versus 52/693 (7.5/100 PY); HR = 2.13; 95%-CI, 1.28-3.65, p = .002) with stroke rates 67% and 68% lower than anticipated by preprocedural CHADS2 score. Combined safety endpoint (major periprocedural complications and major, life-threatening or fatal bleedings) occurred in 22/653 (3.4/100 PY) versus 28/693 (4.0/100 PY); HR = 1.20; 95%-CI, 0.66-2.20, p = .52). CONCLUSIONS: Compared with patients at low risk of stroke, LAAC with Amplatzer devices is associated with similar safety and efficacy in high-risk patients in our study.

Percutaneous mechanical circulatory support from the collaborative multicenter Mechanical Unusual Support in TAVI (MUST) Registry.

OBJECTIVES: To evaluate the use and outcomes of percutaneous mechanical circulatory support (pMCS) utilized during transcatheter aortic valve implantation (TAVI) from high-volume centers. METHODS AND RESULTS: Our international multicenter registry including 13 high-volume TAVI centers with 87 patients (76.5 ± 11.8 years, 63.2% men) who underwent TAVI for severe aortic stenosis and required pMCS (75.9% VA-ECMO, 19.5% Impella CP, 4.6% TandemHeart) during the procedure (prior to TAVI 39.1%, emergent rescue 50.6%, following TAVI 10.3%). The procedures were considered high-risk, with 50.6% having severe left ventricular dysfunction, 24.1% biventricular dysfunction, and 32.2% severe pulmonary hypertension. In-hospital and 1-year mortality were 27.5% and 49.4%, respectively. Patients with prophylactic hemodynamic support had lower periprocedural mortality compared to patients with rescue insertion of pMCS (log rank = 0.013) and patients who did not undergo cardiopulmonary resuscitation during the TAVI procedure had better short and long term survival (log rank <0.001 and 0.015, respectively). CONCLUSIONS: Given the overall survival rate and low frequency of pMCS-related complications, our study results support the use of pMCS prophylactically or during the course of TAVI (bailout) in order to improve clinical outcomes in high-risk procedures or in case of acute life-threatening hemodynamic collapse.

Is it safe to irradiate the newest generation of ventricular assist devices? A case report and systematic literature review.

An increasing number of mechanical assist devices, especially left ventricular assist devices (VADs), are being implanted for prolonged periods and as destination therapy. Some VAD patients require radiotherapy due to concomitant oncologic morbidities, including thoracic malignancies. This raises the potential of VAD malfunction via radiation-induced damage. So far, only case reports and small case series on radiotherapy have been published, most of them on HeartMate II (HMII, Abbott, North Chicago, IL, USA). Significantly, the effects of irradiation on the HeartMate 3 (HM3, Abbott) remain undefined, despite the presence of controller components engineered within the pump itself. We report the first case of a patient with a HM3 who successfully underwent stereotactic hypofractionated radiotherapy due to an early-stage non-small-cell lung cancer. The patient did not suffer from any complications, including toxicity or VAD malfunction. Based on this case report and on published literature, we think that performing radiotherapy after VAD implantation with the aid of a multidisciplinary team could be performed, but more in vitro studies and cases series are needed to reinforce this statement.

Quantitative Flow Ratio to Predict Non-Target-Vessel Events Before Planned Staged Percutaneous Coronary Intervention in Patients With Acute Coronary Syndrome.

BACKGROUND: The optimal time point of staged percutaneous coronary intervention (PCI) among patients with acute coronary syndrome (ACS) remains a matter of debate. Quantitative flow ratio (QFR) is a novel noninvasive method to assess the hemodynamic significance of coronary stenoses. We aimed to investigate whether QFR could refine the timing of staged PCI of non-target vessels (non-TVs) on top of clinical judgment for patients with ACS. METHODS AND RESULTS: For this cohort study, patients with ACS from Bern University Hospital, Switzerland, scheduled to undergo out-of-hospital non-TV staged PCI were eligible. The primary end point was the composite of non-TV myocardial infarction and urgent unplanned non-TV PCI before planned staged PCI. The association between lowest QFR per patient measured in the non-TV (from index angiogram) and the primary end point was assessed using multivariable adjusted Cox proportional hazards regressions with QFR included as linear or penalized spline (nonlinear) term. QFR was measured in 1093 of 1432 patients with ACS scheduled to undergo non-TV staged PCI. Median time to staged PCI was 28 days. The primary end point occurred in 5% of the patients. In multivariable analysis (1018 patients), there was no independent association between non-TV QFR and the primary end point (hazard ratio, 0.87 [95% CI, 0.69-1.05] per 0.1 increase; P=0.125; nonlinear P=0.648). CONCLUSIONS: In selected patients with ACS scheduled to undergo staged PCI at a median of 4 weeks after index PCI, QFR did not emerge as an independent predictor of non-TV events before planned staged PCI. Thus, this study does not provide conceptual evidence that QFR is helpful to refine the timing of staged PCI on top of clinical judgment. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02241291.

Training-related modulations of the autonomic nervous system in endurance athletes: is female gender cardioprotective?

The risk of sudden death is increased in athletes with a male predominance. Regular physical activity increases vagal tone, and may protect against exercise-induced ventricular arrhythmias. We investigated training-related modulations of the autonomic nervous system in female and male endurance athletes. Runners of a 10-mile race were invited. Of 873 applicants, 68 female and 70 male athletes were randomly selected and stratified according to their average weekly training hours in a low (≤4 h) and high (>4 h) volume training group. Analysis of heart rate variability was performed over 24 h. Spectral components (high frequency [HF] and low frequency [LF] power in normalized units) were analyzed for hourly 5 min segments and averaged for day- and nighttime. One hundred and fourteen athletes (50 % female, mean age 42 ± 7 years) were included. No significant gender difference was observed for training volume and 10-mile race time. Over the 24-h period, female athletes exhibited a higher HF and lower LF power for each hourly time-point. Female gender and endurance training hours were independent predictors of a higher HF and lower LF power. In female athletes, higher training hours were associated with a higher HF and lower LF power during nighttime. In male athletes, the same was true during daytime. In conclusion, female and male athletes showed a different circadian pattern of the training-related increase in markers of vagal tone. For a comparable amount of training volume, female athletes maintained their higher markers of vagal tone, possibly indicating a superior protection against exercise-induced ventricular arrhythmias.

Dynamics of bacterial pathogens at the driveline exit site in patients with ventricular assist devices: A prospective, observational, single-center cohort study.

BACKGROUND: Driveline infections (DLIs) at the exit site are frequent in patients with left ventricular assist devices (LVADs). The dynamics from colonization to infection are yet to be investigated. We combined systematic swabbing at the driveline exit site and genomic analyses to study the dynamics of bacterial pathogens and get insights into DLIs pathogenesis. METHODS: A prospective, observational, single-center cohort study at the University Hospital of Bern, Switzerland was performed. Patients with LVAD were systematically swabbed at the driveline exit site between June 2019 and December 2021, irrespective of signs and symptoms of DLI. Bacterial isolates were identified and a subset was whole-genome sequenced. RESULTS: Fifty-three patients were screened, of which 45 (84.9%) were included in the final population. Bacterial colonization at the driveline exit site without manifestation of DLI was frequent and observed in 17 patients (37.8%). Twenty-two patients (48.9%) developed at least one DLI episode over the study period. Incidence of DLIs reached 2.3 cases per 1000 LVAD days. The majority of the organisms cultivated from exit sites were Staphylococcus species. Genome analysis revealed that bacteria persisted at the driveline exit site over time. In four patients, transition from colonization to clinical DLI was observed. CONCLUSIONS: Our study is the first to address bacterial colonization in the LVAD-DLI setting. We observed that bacterial colonization at the driveline exit site was a frequent phenomenon, and in a few cases, it preceded clinically relevant infections. We also provided acquisition of hospital-acquired multidrug-resistant bacteria and the transmission of pathogens between patients.

Symptomatic vs. non-symptomatic device-related thrombus after LAAC: a sub-analysis from the multicenter EUROC-DRT registry.

BACKGROUND: Device-related thrombus (DRT) after left atrial appendage closure (LAAC) is associated with adverse outcomes, i.e. ischemic stroke or systemic embolism (SE). Data on predictors of stroke/SE in the context of DRT are limited. AIMS: This study aimed to identify predisposing factors for stroke/SE in DRT patients. In addition, the temporal connection of stroke/SE to DRT diagnosis was analyzed. METHODS: The EUROC-DRT registry included 176 patients, in whom DRT after LAAC were diagnosed. Patients with symptomatic DRT, defined as stroke/SE in the context of DRT diagnosis, were compared against patients with non-symptomatic DRT. Baseline characteristics, anti-thrombotic regimens, device position, and timing of stroke/SE were compared. RESULTS: Stroke/SE occurred in 25/176 (14.2%) patients diagnosed with DRT (symptomatic DRT). Stroke/SE occurred after a median of 198 days (IQR 37-558) after LAAC. In 45.8% stroke/SE occurred within one month before/after DRT diagnosis (DRT-related stroke). Patients with symptomatic DRT had lower left ventricular ejection fractions (50.0 ± 9.1% vs. 54.2 ± 11.0%, p = 0.03) and higher rates of non-paroxysmal atrial fibrillation (84.0% vs. 64.9%, p = 0.06). Other baseline parameters and device positions were not different. Most ischemic events occurred among patients with single antiplatelet therapy (50%), however, stroke/SE was also observed under dual antiplatelet therapy (25%) or oral anticoagulation (20%). CONCLUSION: Stroke/SE are documented in 14.2% and occur both in close temporal relation to the DRT finding and chronologically independently therefrom. Identification of risk factors remains cumbersome, putting all DRT patients at substantial risk for stroke/SE. Further studies are necessary to minimize the risk of DRT and ischemic events.

2-year outcomes of MitraClip as a bridge to heart transplantation: The international MitraBridge registry.

BACKGROUND: In the first report from the MitraBridge registry, MitraClip as a bridge to heart transplantation (HTx) proved to be at 1-year an effective treatment strategy for 119 patients with advanced heart failure (HF) who were potential candidates for HTx. We aimed to determine if benefits of MitraClip procedure as a bridge-to-transplant persist up to 2-years. METHODS: By the end of the enrollment period, a total of 153 advanced HF patients (median age 59 years, left ventricular ejection fraction 26.9 ± 7.7%) with significant secondary mitral regurgitation, who were potential candidates for HTx and were treated with MitraClip as a bridge-to-transplant strategy, were included in the MitraBridge registry. The primary endpoint was the 2-year composite adverse events rate of all-cause death, first hospitalization for HF, urgent HTx or LVAD implantation. RESULTS: Procedural success was achieved in 89.5% of cases. Thirty-day mortality was 0%. At 2-year, Kaplan-Meier estimates of freedom from primary endpoint was 47%. Through 24 months, the annualized rate of HF rehospitalization per patient-year was 44%. After an overall median follow-up time of 26 (9-52) months, elective HTx was successfully performed in 30 cases (21%), 19 patients (13.5%) maintained or obtained the eligibility for transplant, and 32 patients (22.5%) no longer had an indication for HTx because of significant clinical improvement. CONCLUSIONS: After 2-years of follow-up, the use of MitraClip as a bridge-to-transplant was confirmed as an effective strategy, allowing elective HTx or eligibility for transplant in one third of patients, and no more need for transplantation in 22.5% of cases.

Diagnostic performance of cardiac magnetic resonance segmental myocardial strain for detecting microvascular obstruction and late gadolinium enhancement in patients presenting after a ST-elevation myocardial infarction.

Background: Microvascular obstruction (MVO) and Late Gadolinium Enhancement (LGE) assessed in cardiac magnetic resonance (CMR) are associated with adverse outcome in patients with ST-elevation myocardial infarction (STEMI). Our aim was to analyze the diagnostic performance of segmental strain for the detection of MVO and LGE. Methods: Patients with anterior STEMI, who underwent additional CMR were enrolled in this sub-study of the CARE-AMI trial. Using CMR feature tracking (FT) segmental circumferential peak strain (SCS) was measured and the diagnostic performance of SCS to discriminate MVO and LGE was assessed in a derivation and validation cohort. Results: Forty-eight STEMI patients (62 ± 12 years old), 39 (81%) males, who underwent CMR (i.e., mean 3.0 ± 1.5 days) after primary percutaneous coronary intervention (PCI) were included. All patients presented with LGE and in 40 (83%) patients, MVO was additionally present. Segments in all patients were visually classified and 146 (19%) segments showed MVO (i.e., LGE+/MVO+), 308 (40%) segments showed LGE and no MVO (i.e., LGE+/MVO-), and 314 (41%) segments showed no LGE (i.e., LGE-). Diagnostic performance of SCS for detecting MVO segments (i.e., LGE+/MVO+ vs. LGE+/MVO-, and LGE-) showed an AUC = 0.764 and SCS cut-off value was -11.2%, resulting in a sensitivity of 78% and a specificity of 67% with a positive predictive value (PPV) of 30% and a negative predictive value (NPV) of 94% when tested in the validation group. For LGE segments (i.e., LGE+/MVO+ and LGE+/MVO- vs. LGE-) AUC = 0.848 and SCS with a cut-off value of -13.8% yielded to a sensitivity of 76%, specificity of 74%, PPV of 81%, and NPV of 70%. Conclusion: Segmental strain in STEMI patients was associated with good diagnostic performance for detection of MVO+ segments and very good diagnostic performance of LGE+ segments. Segmental strain may be useful as a potential contrast-free surrogate marker to improve early risk stratification in patients after primary PCI.

Long-term risk of unplanned percutaneous coronary intervention after transcatheter aortic valve replacement.

BACKGROUND: Coronary access after transcatheter aortic valve replacement (TAVR) can be challenging and complicate percutaneous coronary intervention (PCI). AIMS: We aimed to investigate the incidence, characteristics, and predictors of unplanned PCI after TAVR. METHODS: In a single-centre registry, TAVR candidates were systematically screened for concomitant coronary artery disease (CAD) through the use of coronary angiography prior to TAVR. Rates of unplanned PCI were prospectively collected and independently adjudicated. RESULTS: Among 3,015 patients undergoing TAVR between August 2007 and December 2020, 67 patients (2.2%) underwent unplanned PCI after TAVR. The indication for unplanned PCI was acute coronary syndrome in more than half of the cases. Patients with unplanned PCI were younger (80.2±6.5 years vs 81.9±6.4 years; p=0.028) and more likely to be male (75% vs 50%; p<0.001) than those without unplanned PCI. In a multivariable analysis, the number of diseased vessels, male sex, and younger age were independently associated with an increased risk of unplanned PCI. The cumulative incidence rates of unplanned PCI at 1, 5, and 10 years were 0.1%, 0.4%, and 0.6% in patients with no CAD at the time of TAVR, 0.7%, 2.5%, and 3.4% in patients with single-vessel disease, and 1.5%, 5.4%, and 7.4% in patients with multivessel disease, respectively. CONCLUSIONS: The lifetime risk of unplanned PCI after TAVR is low in patients with no CAD at the time of TAVR but accumulates over time in patients with known CAD, particularly multivessel disease. CLINICALTRIALS: gov: NCT01368250.

Clinical and echocardiographic risk factors for device-related thrombus after left atrial appendage closure: an analysis from the multicenter EUROC-DRT registry.

BACKGROUND: Data on Device-related Thrombus (DRT) after left atrial appendage closure (LAAC) remain scarce. This study aimed to investigate risk factors for DRT from centers reporting to the EUROC-DRT registry. METHODS: We included 537 patients (112 with DRT and 425 without DRT) who had undergone LAAC between 12/2008 and 04/2019. Baseline and implantation characteristics, anti-thrombotic treatment and clinical outcomes were compared between both groups in uni- and multivariate analyses. Additional propensity-score matching (PSM) was conducted to focus on the role of implantation characteristics. RESULTS: Patients with DRT showed higher rates of previous stroke/transient ischemic attack (TIA) (49.1% vs. 34.7%, p < 0.01), spontaneous echocardiographic contrast (SEC) (44.9% vs. 27.7%, p < 0.01) and lower left atrial appendage (LAA) peak emptying velocity (35.4 ± 18.5 vs. 42.4 ± 18.0 cm/s, p = 0.02). Occluders implanted in DRT patients were larger (25.5 ± 3.8 vs. 24.6 ± 3.5 mm, p = 0.03) and implanted deeper in the LAA (mean depth: 7.6 ± 4.7 vs. 5.7 ± 4.7 mm, p < 0.01). Coverage of the appendage ostium was achieved less often in DRT patients (69.5% vs. 81.5%, p < 0.01), while DRT patients were less frequently on oral anticoagulation (7.1% vs. 16.7%, p < 0.01). Multivariate analysis identified age, prior stroke/TIA and SEC as independent risk factors for DRT. After PSM, implantation depth was found to be predictive. Rates of stroke/TIA were higher in DRT patients (13.5% vs. 3.8%, Hazard Ratio: 4.21 [95%-confidence interval: 1.88-9.49], p < 0.01). CONCLUSIONS: DRT after LAAC is associated with adverse outcome and appears to be of multifactorial origin, depending on patient characteristics, anticoagulation regimen and device position.

Isolation and characterization of bacteriophages from the human skin microbiome that infect Staphylococcus epidermidis.

Phage therapy might be a useful approach for the treatment of nosocomial infections; however, only few lytic phages suitable for this application are available for the opportunistic pathogen, Staphylococcus epidermidis. In the current study, we developed an efficient method to isolate bacteriophages present within the human skin microbiome, by using niche-specific S. epidermidis as the host for phage propagation. Staphylococcus epidermidis was identified on the forehead of 92% of human subjects tested. These isolates were then used to propagate phages present in the same skin sample. Plaques were observable on bacterial lawns in 46% of the cases where S. epidermidis was isolated. A total of eight phage genomes were genetically characterized, including the previously described phage 456. A total of six phage sequences were unique, and spanned each of the major staphylococcal phage families; Siphoviridae (n = 3), Podoviridae (n = 1) and Myoviridae (n = 2). One of the myoviruses (vB_SepM_BE06) was identified on the skin of three different humans. Comparative analysis identified novel genes including a putative N-acetylmuramoyl-L-alanine amidase gene. The host-range of each unique phage was characterized using a panel of diverse staphylococcal strains (n = 78). None of the newly isolated phages infected more than 52% of the S. epidermidis strains tested (n = 44), and non-S. epidermidis strains where rarely infected, highlighting the narrow host-range of the phages. One of the phages (vB_SepM_BE04) was capable of killing staphylococcal cells within biofilms formed on polyurethane catheters. Uncovering a richer diversity of available phages will likely improve our understanding of S. epidermidis-phage interactions, which will be important for future therapy.

Effect of Paroxetine-Mediated G-Protein Receptor Kinase 2 Inhibition vs Placebo in Patients With Anterior Myocardial Infarction: A Randomized Clinical Trial.

Importance: Left ventricular remodeling following acute myocardial infarction results in progressive myocardial dysfunction and adversely affects prognosis. Objective: To investigate the efficacy of paroxetine-mediated G-protein-coupled receptor kinase 2 inhibition to mitigate adverse left ventricular remodeling in patients presenting with acute myocardial infarction. Design, Setting, and Participants: This double-blind, placebo-controlled randomized clinical trial was conducted at Bern University Hospital, Bern, Switzerland. Patients with acute anterior ST-segment elevation myocardial infarction with left ventricular ejection fraction (LVEF) of 45% or less were randomly allocated to 2 study arms between October 26, 2017, and September 21, 2020. Interventions: Patients in the experimental arm received 20 mg of paroxetine daily; patients in the control group received a placebo daily. Both treatments were provided for 12 weeks. Main Outcomes and Measures: The primary end point was the difference in patient-level improvement of LVEF between baseline and 12 weeks as assessed by cardiac magnetic resonance tomography. Secondary end points were changes in left ventricular dimensions and late gadolinium enhancement between baseline and follow-up. Results: Fifty patients (mean [SD] age, 62 [13] years; 41 men [82%]) with acute anterior myocardial infarction were randomly allocated to paroxetine or placebo, of whom 38 patients underwent cardiac magnetic resonance imaging both at baseline and 12 weeks. There was no difference in recovery of LVEF between the experimental group (mean [SD] change, 4.0% [7.0%]) and the control group (mean [SD] change, 6.3% [6.3%]; mean difference, -2.4% [95% CI, -6.8% to 2.1%]; P = .29) or changes in left ventricular end-diastolic volume (mean difference, 13.4 [95% CI, -12.3 to 39.0] mL; P = .30) and end-systolic volume (mean difference, 11.4 [95% CI, -3.6 to 26.4] mL; P = .13). Late gadolinium enhancement as a percentage of the total left ventricular mass decreased to a larger extent in the experimental group (mean [SD], -13.6% [12.9%]) compared with the control group (mean [SD], -4.5% [9.5%]; mean difference, -9.1% [95% CI, -16.6% to -1.6%]; P = .02). Conclusions and Relevance: In this trial, treatment with paroxetine did not improve LVEF after myocardial infarction compared with placebo. Trial Registration: ClinicalTrials.gov Identifier: NCT03274752.

Device-Related Thrombus After Left Atrial Appendage Closure: Data on Thrombus Characteristics, Treatment Strategies, and Clinical Outcomes From the EUROC-DRT-Registry.

BACKGROUND: Left atrial appendage closure is an established therapy in patients with atrial fibrillation. Although device-related thrombosis (DRT) is relatively rare, it is potentially linked to adverse events. As data on DRT characteristics, outcome, and treatment regimen are scarce, we aimed to assess these questions in a multicenter approach. METHODS: One hundred fifty-six patients with the diagnosis of DRT after left atrial appendage closure were included in the multinational EUROC-DRT registry. Baseline characteristics included clinical and echocardiographic data. After inclusion, all patients underwent further clinical and echocardiographic follow-up to assess DRT dynamics, treatment success, and outcome. RESULTS: DRT was detected after a median of 93 days (interquartile range, 54­161 days) with 17.9% being detected >6 months after left atrial appendage closure. Patients with DRT were at high ischemic and bleeding risk (CHA2DS2-VASc 4.5±1.7, HAS-BLED 3.3±1.2) and had nonparoxysmal atrial fibrillation (67.3%), previous stroke (53.8%), and spontaneous echo contrast (50.6%). The initial treatment regimens showed comparable resolution rates (antiplatelet monotherapy: 57.1%, dual antiplatelet therapy: 85.7%, vitamin K antagonists: 80.0%, novel oral anticoagulants: 75.0%, and heparin: 68.6%). After intensification or switch of treatment, complete DRT resolution was achieved in 79.5% of patients. Two-year follow-up revealed a high risk of mortality (20.0%) and ischemic stroke (13.8%) in patients with DRT. Patients with incomplete DRT resolution showed numerically higher stroke rates and increased mortality rates (stroke: 17.6% versus 12.3%, P=0.29; mortality: 31.3% versus 13.1%, P=0.05). CONCLUSIONS: A substantial proportion of DRT is detected >6 months after left atrial appendage closure, highlighting the need for imaging follow-up. Patients with DRT appear to be at a high risk for stroke and mortality. While DRT resolution was achieved in most patients, incomplete DRT resolution appeared to identify patients at even higher risk. Optimal DRT diagnostic criteria and treatment regimens are warranted.

Left atrial appendage closure versus medical therapy in patients with atrial fibrillation: the APPLY study.

AIMS: Left atrial appendage closure (LAAC) with AMPLATZER occluders is used for stroke prevention in atrial fibrillation (AF). Net clinical benefit compared to medical therapy has not been tested. The aim of this study was to test whether long-term clinical outcome after LAAC with AMPLATZER occluders may be similar to medical therapy. METHODS AND RESULTS: Five hundred consecutive patients who underwent LAAC with AMPLATZER occluders were compared to 500 patients with medical therapy by propensity score matching. The primary efficacy endpoint was a composite of stroke, systemic embolism and cardiovascular/unexplained death. The primary safety endpoint consisted of major procedural adverse events and major bleedings. For assessment of net clinical benefit, all of the above-mentioned hazards were combined. After 2,645 patient-years at a mean follow-up of 2.7±1.5 years, the primary efficacy endpoint was reached by 75/1,342, 5.6% in the LAAC group versus 102/1,303, 7.8% per 100 patient-years (hazard ratio [HR] 0.70, 95% confidence interval [CI]: 0.53-0.95, p=0.026). The primary safety endpoint occurred in 48/1,342, 3.6% versus 60/1,303, 4.6% per 100 patient-years (HR 0.80, 95% CI: 0.55-1.18, p=0.21), and the combined hazard endpoint in 109/1,342, 8.1% versus 142/1,303, 10.9% per 100 patient-years (HR 0.76, 95% CI: 0.60-0.97, p=0.018). Patients receiving LAAC demonstrated lower rates of both all-cause and cardiovascular mortality (111/1,342, 8.3% vs 151/1,303, 11.6% per 100 patient-years [HR 0.72, 95% CI: 0.56-0.92, p=0.005] and 54/1,342, 4.0% vs 84/1,303, 6.5% per 100 patient-years [HR 0.64, 95% CI: 0.46-0.89, p=0.007]). CONCLUSIONS: LAAC with AMPLATZER devices showed a net clinical benefit over medical therapy by superior efficacy, similar safety and a benefit in all-cause and cardiovascular mortality.

MitraClip in secondary mitral regurgitation as a bridge to heart transplantation: 1-year outcomes from the International MitraBridge Registry.

BACKGROUND: Patients awaiting heart transplantation (HTx) often need bridging therapies to reduce worsening and progression of underlying disease. Limited data are available regarding the use of the MitraClip procedure in secondary mitral regurgitation for this clinical condition. METHODS: We evaluated an international, multicenter (17 centers) registry including 119 patients (median age: 58 years) with moderate-to-severe or severe secondary mitral regurgitation and advanced heart failure (HF) (median left ventricular ejection fraction: 26%) treated with MitraClip as a bridge strategy according to 1 of the following criteria: (1) patients active on HTx list (in list group) (n = 31); (2) patients suitable for HTx but awaiting clinical decision (bridge to decision group) (n = 54); or (3) patients not yet suitable for HTx because of potentially reversible relative contraindications (bridge to candidacy group) (n = 34). RESULTS: Procedural success was achieved in 87.5% of cases, and 30-day survival was 100%. At 1 year, Kaplan-Meier estimates of freedom from the composite primary end-point (death, urgent HTx or left ventricular assist device implantation, first rehospitalization for HF) was 64%. At the time of last available follow-up (median: 532 days), 15% of patients underwent elective transplant, 15.5% remained or could be included in the HTx waiting list, and 23.5% had no more indication to HTx because of clinical improvement. CONCLUSIONS: MitraClip procedure as a bridge strategy to HTx in patients with advanced HF with significant mitral regurgitation was safe, and two thirds of patients remained free from adverse events at 1 year. These findings should be considered exploratory and hypothesis-generating to guide further study for percutaneous intervention in high-risk patients with advanced HF.