Impact of tafamidis on myocardial function and CMR tissue characteristics in transthyretin amyloid cardiomyopathy.

AIMS: Tafamidis improves clinical outcomes in transthyretin amyloid cardiomyopathy (ATTR-CM), yet how tafamidis affects cardiac structure and function remains poorly described. This study prospectively analysed the effect of tafamidis on 12-month longitudinal changes in cardiac structure and function by cardiac magnetic resonance (CMR) compared with the natural course of disease in an untreated historic control cohort. METHODS AND RESULTS: ATTR-CM patients underwent CMR at tafamidis initiation and at 12 months. Untreated patients with serial CMRs served as reference to compare biventricular function, global longitudinal strain (GLS), LV mass and extracellular volume fraction (ECV). Thirty-six tafamidis-treated (n = 35; 97.1% male) and 15 untreated patients (n = 14; 93.3% male) with a mean age of 78.3 ± 6.5 and 76.9 ± 6.5, respectively, and comparable baseline characteristics were included. Tafamidis was associated with preserving biventricular function (LVEF (%): 50.5 ± 12 to 50.7 ± 11.5, P = 0.87; RVEF (%): 48.2 ± 10.4 to 48.2 ± 9.4, P = 0.99) and LV-GLS (-9.6 ± 3.2 to -9.9 ± 2.4%; P = 0.595) at 12 months, while a significantly reduced RV-function (50.8 ± 7.3 to 44.2 ± 11.6%, P = 0.028; P (change over time between groups) = 0.032) and numerically worsening LVGLS (-10.9 ± 3.3 to -9.1 ± 2.9%, P = 0.097; P (change over time between groups) = 0.048) was observed without treatment. LV mass significantly declined with tafamidis (184.7 ± 47.7 to 176.5 ± 44.3 g; P = 0.011), yet remained unchanged in untreated patients (163.8 ± 47.5 to 171.2 ± 39.7 g P = 0.356, P (change over time between groups) = 0.027). Irrespective of tafamidis, ECV and native T1-mapping did not change significantly from baseline to 12-month follow-up (P > 0.05). CONCLUSIONS: Compared with untreated ATTR-CM patients, initiation of tafamidis preserved CMR-measured biventricular function and reduced LV mass at 12 months. ECV and native T1-mapping did not change significantly comparable to baseline in both groups.

Prognostic Value of [99mTc]Tc-DPD Quantitative SPECT/CT in Patients with Suspected and Confirmed Amyloid Transthyretin-Related Cardiomyopathy and Preserved Left Ventricular Function.

Quantitative 99mTc-3,3-diphosphono-1,2-propanodicarboxylic acid ([99mTc]Tc-DPD) SPECT may be used for risk-stratifying patients with amyloid transthyretin-related cardiomyopathy (ATTR-CM). We aimed to analyze the predictive value of quantitative [99mTc]Tc-DPD SPECT/CT in suspected and confirmed ATTR-CM according to different disease stages. Methods: The study enrolled consecutive patients with suspected ATTR-CM who were referred to a single tertiary center and underwent quantitative [99mTc]Tc-DPD SPECT/CT allowing SUVmax and SUVpeak analysis. Patients were divided into 2 groups according to left ventricular ejection fraction (LVEF) at baseline (i.e., ≥50% and <50%). Clinical, laboratory, and echocardiographic parameters and major adverse cardiac events (i.e., all-cause death, sustained ventricular tachyarrhythmia, hospitalization for heart failure, implantation of a cardioverter defibrillator) were investigated for any correlation with quantitative uptake values. Results: In total, 144 patients with suspected ATTR-CM were included in the study (98 with LVEF ≥ 50% and 46 with LVEF < 50%), of whom 99 were diagnosed with ATTR-CM (68.8%; 69 with LVEF ≥ 50% and 30 with LVEF < 50%). A myocardial SUVmax of at least 7 was predictive of major adverse cardiac events at 21.9 ± 13.0 mo of follow-up (hazard ratio, 2.875; 95% CI, 1.23-6.71; P = 0.015) in patients with suspected or confirmed ATTR-CM (global χ2 = 6.892, P = 0.02) and an LVEF of at least 50%. SUVmax was not predictive in patients with an LVEF of less than 50% and suspected or confirmed ATTR-CM. Conclusion: In patients with suspected or confirmed ATTR-CM and preserved LVEF, representing an early disease stage, quantitative [99mTc]Tc-DPD SPECT should be considered to improve early-stage risk stratification.

Routine 4D Cardiac CT to Identify Concomitant Transthyretin Amyloid Cardiomyopathy in Older Adults with Severe Aortic Stenosis.

Background Transthyretin amyloid cardiomyopathy (ATTR-CM) often coexists with severe aortic stenosis (AS). Although strain analysis from cardiac MRI and echocardiography was demonstrated to predict coexisting ATTR-CM, comparable data from four-dimensional (4D) cardiac CT are lacking despite wide availability. Purpose To evaluate the diagnostic performance of 4D cardiac CT-derived parameters in identifying ATTR-CM in older adults considered for transcatheter aortic valve implantation (TAVI). Materials and Methods This prospective single-center screening study for ATTR-CM included consecutive patients with severe AS considered for TAVI who underwent 4D cardiac CT between August 2019 and August 2021 approximately 1 day before technetium 99m (99mTc) 3,3-diphosphono-1,2-propanodicarboxylic-acid (DPD) scintigraphy. The diagnostic performance of CT-based left ventricular (LV), right ventricular, and left atrial dimensions, ejection fraction (EF), and myocardial strain were evaluated against 99mTc-DPD scintigraphy as the reference standard to identify ATTR-CM. Predictors and an unweighted cardiac CT score were validated with internal bootstrapping. The assignment of variables to the score was based on cutoff values achieving the highest Youden index J. Results Among 263 participants (mean age, 83 years ± 4.6 [SD]; 149 male and 114 female participants), 99mTc-DPD scintigraphy (Perugini grade 2 or 3) confirmed coexisting ATTR-CM in 27 (10.3%). CT-derived LV mass index, LV and LA global longitudinal strain (GLS), and relative apical longitudinal strain each predicted the presence of ATTR-CM with an area under the curve (AUC) of at least 0.70. Implementing these parameters with cutoff values of 81 g/m2 or higher, -14.9% or higher, less than 11.5%, and 1.7 or higher in the CT score, respectively, yielded high diagnostic performance (AUC = 0.89; 95% CI: 0.81, 0.94; P < .001) robust to internal bootstrapping validation (AUC = 0.88; 95% CI: 0.82, 0.94). If two criteria were fulfilled, the sensitivity and specificity in the detection of ATTR-CM were 96.3% (95% CI: 81.0, 99.9) and 58.9% (95% CI: 52.3, 65.2), respectively. Conclusion When compared against 99mTc-DPD scintigraphy as the reference standard, routine 4D cardiac CT in older adults considered for TAVI provided high diagnostic performance in the detection of concomitant ATTR-CM by assessing LV and left atrial GLS, relative apical longitudinal strain, and LV mass index. ClinicalTrials.gov registration no.: NCT04061213 © RSNA, 2023 Supplemental material is available for this article. See also the editorial by Tavakoli and Onder in this issue.

Amyloid Transthyretin Cardiomyopathy in Elderly Patients With Aortic Stenosis Undergoing Transcatheter Aortic Valve Implantation.

Background The prevalence of calcific aortic stenosis and amyloid transthyretin cardiomyopathy (ATTR-CM) increase with age, and they often coexist. The objective was to determine the prevalence of ATTR-CM in patients with severe aortic stenosis and evaluate differences in presentations and outcomes of patients with concomitant ATTR-CM undergoing transcatheter aortic valve implantation. Methods and Results Prospective screening for ATTR-CM with Technetium99-3,3-diphosphono-1,2-propanodicarboxylic acid bone scintigraphy was performed in 315 patients referred with severe aortic stenosis between August 2019 and August 2021. Myocardial Technetium99-3,3-diphosphono-1,2-propanodicarboxylic acid tracer uptake was detected in 34 patients (10.8%), leading to a diagnosis of ATTR-CM in 30 patients (Perugini ≥2: 9.5%). Age (85.7±4.9 versus 82.8±4.5; P=0.001), male sex (82.4% versus 57.7%; P=0.005), and prior carpal tunnel surgery (17.6% versus 4.3%; P=0.007) were associated with coexisting ATTR-CM, as were ECG (discordant QRS voltage to left ventricular wall thickness [42% versus 12%; P<0.001]), echocardiographic (left ventricular ejection fraction 48.8±12.8 versus 58.4±10.8; P<0.001; left ventricular mass index, 144.4±45.8 versus 117.2±34.4g/m2; P<0.001), and hemodynamic parameters (mean aortic valve gradient, 23.4±12.6 versus 35.5±16.6; P<0.001; mean pulmonary artery pressure, 29.5±9.7 versus 25.8±9.5; P=0.037). Periprocedural (cardiovascular death: hazard ratio [HR], 0.71 [95% CI, 0.04-12.53]; stroke: HR, 0.46 [95% CI, 0.03-7.77]; pacemaker implantation: HR, 1.54 [95% CI, 0.69-3.43]) and 1-year clinical outcomes (cardiovascular death: HR, 1.04 [95% CI, 0.37-2.96]; stroke: HR, 0.34 [95% CI, 0.02-5.63]; pacemaker implantation: HR, 1.50 [95% CI, 0.67-3.34]) were similar between groups. Conclusions Coexisting ATTR-CM was observed in every 10th elderly patient with severe aortic stenosis referred for therapy. While patients with coexisting pathologies differ in clinical presentation and echocardiographic and hemodynamic parameters, peri-interventional risk and early clinical outcomes were comparable up to 1 year after transcatheter aortic valve implantation. REGISTRATION URL: https://www.clinicaltrials.gov. Unique identifier: NCT04061213.

Association of atrial fibrillation with survival in patients with low-flow low-gradient aortic stenosis with preserved ejection fraction undergoing TAVI.

AIMS: There is limited evidence on the prognostic significance of atrial fibrillation (AF) in patients with low flow, low gradient aortic stenosis with preserved ejection fraction (LFLG-pEF AS). We aimed to evaluate the recovery of stroke volume after transcatheter aortic valve implantation (TAVI) and clinical outcomes in patients with LFLG-pEF AS stratified by presence or absence of AF. METHODS AND RESULTS: In a prospective TAVI registry, patients with preserved left ventricular ejection fraction (LVEF ≥ 50%) were stratified according to flow-gradient status and presence of AF. Among 2 259 TAVI patients with preserved LVEF between August 2007 and June 2021, 765 had high-gradient AS (HG AS) and 444 had LFLG-pEF AS. AF was observed in 199 patients with HG AS (26.0%) and 190 patients with LFLG-pEF AS (42.8%). At 1 year, SVi was significantly improved in LFLG-pEF AS patients without AF, while SVi remained low in patients with AF (from 25.9 ± 8.5 mL/m2 to 37.2 ± 9.9 mL/m2 and from 26.8 ± 5.1 mL/m2 to 26.1 ± 9.1 mL/m2, respectively). LFLG-pEF AS patients with AF had an increased risk of 1-year all-cause mortality compared with those without AF (HRadjusted 2.57; 95% CI 1.44-4.59). LFLG-pEF AS patients without AF had similar mortality compared with HG AS patients without AF (HRadjusted 0.85; 95% CI 0.49-1.46). CONCLUSIONS: Patients with LFLG-pEF AS and AF experienced no relevant recovery of stroke volume after TAVI, but a more than two-fold increased risk of death compared to patients with HG AS or LFLG-pEF AS without AF. Clinical Trial Registration: https://www.clinicaltrials.gov. NCT01368250.

SGLT2 inhibitor therapy for transthyretin amyloid cardiomyopathy: early tolerance and clinical response to dapagliflozin.

AIMS: Sodium-glucose cotransporter 2 inhibitors (SGLT2i) improve clinical outcomes in heart failure patients with reduced and preserved left ventricular ejection fraction (LVEF), but have not yet been investigated in transthyretin amyloid cardiomyopathy (ATTR-CM). This study aimed to evaluate tolerability, clinical outcomes, and changes in NT-proBNP levels and glomerular filtration rate (GFR) in ATTR-CM patients treated with dapagliflozin. METHODS AND RESULTS: Patients with stable, tafamidis-treated ATTR-CM were retrospectively evaluated at the initiation of dapagliflozin and 3 months thereafter. Tafamidis-treated ATTR-CM patients without SGLT2i served as a reference cohort. Overall, SLGT2i therapy was initiated in 34 patients. Seventeen patients with stable disease on tafamidis, who were subsequently started on dapagliflozin, were included in the analysis. Patients selected for SGLT2i presented with signs of advanced disease, evidenced by higher Gillmore disease stage (stage ≥2: 53% vs. 27.5%; P = 0.041), baseline median NT-proBNP [median (IQR) 2668 pg/mL (1314-3451) vs. 1424 (810-2059); P = 0.038] and loop diuretic demand (76.5% vs. 45% of patients; P = 0.044), and lower LVEF (46.6 ± 12.9 vs. 53.7 ± 8.7%; P = 0.019) and GFR (51.8 ± 16.5 vs. 68.5 ± 18.6 mL/min; P = 0.037) compared with the reference cohort. At 3-month follow-up, a numerical decrease in NT-proBNP levels was observed in 13/17 (76.5%) patients in the dapagliflozin (-190 pg/mL, IQR: -1,028-71, P = 0.557) and 27/40 (67.5%) of patients in the control cohort (-115 pg/mL, IQR: -357-105, P = 0.551). Other disease parameters remained stable and no adverse events occurred. CONCLUSIONS: In tafamidis-treated ATTR-CM patients, initiation of dapagliflozin was well tolerated. The efficacy of SGLT2i therapy in patients with ATTR-CM needs to be studied in randomized controlled trials.

Risk and Timing of Noncardiac Surgery After Transcatheter Aortic Valve Implantation.

Importance: Noncardiac surgery after transcatheter aortic valve implantation (TAVI) is a clinical challenge with concerns about safety and optimal management. Objectives: To evaluate perioperative risk of adverse events associated with noncardiac surgery after TAVI by timing of surgery, type of surgery, and TAVI valve performance. Design, Setting, and Participants: This cohort study was conducted using data from a prospective TAVI registry of patients at the tertiary care University Hospital in Bern, Switzerland. All patients undergoing noncardiac surgery after TAVI were identified. Data were analyzed from November through December 2021. Exposures: Timing, clinical urgency, and risk category of noncardiac surgery were assessed among patients who had undergone TAVI and subsequent noncardiac surgery. Main Outcomes and Measures: A composite of death, stroke, myocardial infarction, and major or life-threatening bleeding within 30 days after noncardiac surgery. Results: Among 2238 patients undergoing TAVI between 2013 and 2020, 300 patients (mean [SD] age, 81.8 [6.6] years; 144 [48.0%] women) underwent elective (160 patients) or urgent (140 patients) noncardiac surgery after TAVI and were included in the analysis. Of these individuals, 63 patients (21.0%) had noncardiac surgery within 30 days of TAVI. Procedures were categorized into low-risk (21 patients), intermediate-risk (190 patients), and high-risk (89 patients) surgery. Composite end points occurred within 30 days of surgery among 58 patients (Kaplan-Meier estimate, 19.7%; 95% CI, 15.6%-24.7%). There were no significant differences in baseline demographics between patients with the 30-day composite end point and 242 patients without this end point, including mean (SD) age (81.3 [7.1] years vs 81.9 [6.5] years; P = .28) and sex (25 [43.1%] women vs 119 [49.2%] women; P = .37). Timing (ie, ≤30 days from TAVI to noncardiac surgery), urgency, and risk category of surgery were not associated with increased risk of the end point. Moderate or severe prosthesis-patient mismatch (adjusted hazard ratio [aHR], 2.33; 95% CI, 1.37-3.95; P = .002) and moderate or severe paravalvular regurgitation (aHR, 3.61; 95% CI 1.25-10.41; P = .02) were independently associated with increased risk of the end point. Conclusions and Relevance: These findings suggest that noncardiac surgery may be performed early after successful TAVI. Suboptimal device performance, such as prosthesis-patient mismatch and paravalvular regurgitation, was associated with increased risk of adverse outcomes after noncardiac surgery.

Diagnostic performance of quantitative coronary artery disease assessment using computed tomography in patients with aortic stenosis undergoing transcatheter aortic-valve implantation.

BACKGROUND: Computed tomography angiography (CTA) is a cornerstone in the pre- transcatheter aortic valve replacement (TAVI) assessment. We evaluated the diagnostic performance of CTA and coronary artery calcium score (CACS) for CAD evaluation compared to invasive coronary angiography in a cohort of TAVI patients. METHODS: In consecutive TAVI patients without prior coronary revascularization and device implants, CAD was assessment by quantitative analysis in CTA. (a) Patients with non-evaluable segments were classified as obstructive CAD. (b) In patients with non-evaluable segments a CACS cut-off of 100 was applied for obstructive CAD. The reference standard was quantitative invasive coronary angiography (QCA, i.e. ≥ 50% stenosis). RESULTS: 100 consecutive patients were retrospectively included, age was 82.3 ± 6.5 years and 30% of patients had CAD. In 16% of the patients, adequate visualization of the entire coronary tree (all 16 segments) was possible with CTA, while 84% had at least one segment which was not evaluable for CAD analysis due to impaired image quality. On a per-patient analysis, where patients with low image quality were classified as CAD, CTA showed a sensitivity of 100% (95% CI 88.4-100.0), specificity of 11.4% (95% CI 5.1-21.3), PPV of 32.6% (95% CI 30.8-34.5), NPV of 100% and diagnostic accuracy of 38% (95% CI 28.5-48.3) for obstructive CAD. When applying a combined approach of CTA (in patients with good image quality) and CACS (in patients with low image quality), the sensitivity and NPV remained at 100% and obstructive CAD could be ruled out in 20% of the TAVI patients, versus 8% using CTA alone. CONCLUSION: In routinely acquired pre-TAVI CTA, the image quality was insufficient in a high proportion of patients for the assessment of the entire coronary artery tree. However, when adding CACS in patients with low image quality to quantitative CTA assessment in patients with good image quality, obstructive CAD could be ruled-out in 1/5 of the patients and may therefore constitute a strategy to streamline pre-procedural workup, and reduce risk, radiation and costs in selected TAVI patients without prior coronary revascularization or device implants.

Surgical Treatment of Patients With Infective Endocarditis After Transcatheter Aortic Valve Implantation.

BACKGROUND: The optimal treatment of patients developing infective endocarditis (IE) after transcatheter aortic valve implantation (TAVI) is uncertain. OBJECTIVES: The goal of this study was to investigate the clinical characteristics and outcomes of patients with TAVI-IE treated with cardiac surgery and antibiotics (IE-CS) compared with patients treated with antibiotics alone (IE-AB). METHODS: Crude and inverse probability of treatment weighting analyses were applied for the treatment effect of cardiac surgery vs medical therapy on 1-year all-cause mortality in patients with definite TAVI-IE. The study used data from the Infectious Endocarditis after TAVI International Registry. RESULTS: Among 584 patients, 111 patients (19%) were treated with IE-CS and 473 patients (81%) with IE-AB. Compared with IE-AB, IE-CS was not associated with a lower in-hospital mortality (HRunadj: 0.85; 95% CI: 0.58-1.25) and 1-year all-cause mortality (HRunadj: 0.88; 95% CI: 0.64-1.22) in the crude cohort. After adjusting for selection and immortal time bias, IE-CS compared with IE-AB was also not associated with lower mortality rates for in-hospital mortality (HRadj: 0.92; 95% CI: 0.80-1.05) and 1-year all-cause mortality (HRadj: 0.95; 95% CI: 0.84-1.07). Results remained similar when patients with and without TAVI prosthesis involvement were analyzed separately. Predictors for in-hospital and 1-year all-cause mortality included logistic EuroSCORE I, Staphylococcus aureus, acute renal failure, persistent bacteremia, and septic shock. CONCLUSIONS: In this registry, the majority of patients with TAVI-IE were treated with antibiotics alone. Cardiac surgery was not associated with an improved all-cause in-hospital or 1-year mortality. The high mortality of patients with TAVI-IE was strongly linked to patients' characteristics, pathogen, and IE-related complications.

Self-reported non-adherence to P2Y12 inhibitors in patients undergoing percutaneous coronary intervention: Application of the medication non-adherence academic research consortium classification.

AIMS: The Non-adherence Academic Research Consortium (NARC) has recently developed a consensus-based standardized classification for medication non-adherence in cardiovascular clinical trials. We aimed to assess the prevalence of NARC-defined self-reported non-adherence to P2Y12 inhibitors and its impact on clinical outcomes in patients undergoing percutaneous coronary intervention (PCI). METHODS AND RESULTS: Using a standardized questionnaire administered at 1 year after PCI, we assessed the 4 NARC-defined non-adherence levels including type, decision-maker, reasons, and timing within the Bern PCI registry. The primary endpoint was the patient-oriented composite endpoint (POCE) defined as a composite of death, myocardial infarction, stroke, and any revascularization at 1 year. The recommended P2Y12 inhibitor duration was 12 months. Among 3,896 patients, P2Y12 inhibitor non-adherence was observed in 647 (17%) patients. Discontinuation was permanent in the majority of patients (84%). The decision was mainly driven by a physician (94%), and rarely by patients (6%). The most frequent reason was risk profile change (43%), followed by unlisted reasons (25%), surgery (17%), and adverse events (14%). Non-adherence occurred early (<30 days) in 21%, late (30-180 days) in 45%, and very late (>180 days) in 33%. The majority of POCE events (n = 421/502, 84%) occurred during adherence to the prescribed P2Y12 inhibitor. Permanent discontinuation, doctor-driven non-adherence, and risk profile change emerged as independent predictors for POCE. CONCLUSIONS: In real-world PCI population treated with 1-year DAPT, non-adherence was observed in nearly one-fifth of patients. Non-adherence to P2Y12 inhibitors was associated with worse clinical outcomes, while the risk was related to underlying contexts. CLINICALTRIALS.GOV IDENTIFIER: NCT02241291.

Infective Endocarditis Caused by Staphylococcus aureus After Transcatheter Aortic Valve Replacement.

BACKGROUND: Staphylococcus aureus (SA) has been extensively studied as causative microorganism of surgical prosthetic-valve infective endocarditis (IE). However, scarce evidence exists on SA IE after transcatheter aortic valve replacement (TAVR). METHODS: Data were obtained from the Infectious Endocarditis After TAVR International Registry, including patients with definite IE after TAVR from 59 centres in 11 countries. Patients were divided into 2 groups according to microbiologic etiology: non-SA IE vs SA IE. RESULTS: SA IE was identified in 141 patients out of 573 (24.6%), methicillin-sensitive SA in most cases (115/141, 81.6%). Self-expanding valves were more common than balloon-expandable valves in patients presenting with early SA IE. Major bleeding and sepsis complicating TAVR, neurologic symptoms or systemic embolism at admission, and IE with cardiac device involvement (other than the TAVR prosthesis) were associated with SA IE (P < 0.05 for all). Among patients with IE after TAVR, the likelihood of SA IE increased from 19% in the absence of those risk factors to 84.6% if ≥ 3 risk factors were present. In-hospital (47.8% vs 26.9%; P < 0.001) and 2-year (71.5% vs 49.6%; P < 0.001) mortality rates were higher among patients with SA IE vs non-SA IE. Surgery at the time of index SA IE episode was associated with lower mortality at follow-up compared with medical therapy alone (adjusted hazard ratio 0.46, 95% CI 0.22-0.96; P = 0.038). CONCLUSIONS: SA IE represented approximately 25% of IE cases after TAVR and was associated with very high in-hospital and late mortality. The presence of some features determined a higher likelihood of SA IE and could help to orientate early antibiotic regimen selection. Surgery at index SA IE was associated with improved outcomes, and its role should be evaluated in future studies.

Perivalvular Extension of Infective Endocarditis After Transcatheter Aortic Valve Replacement.

BACKGROUND: Infective endocarditis (IE) following transcatheter aortic valve replacement (TAVR) has been associated with a dismal prognosis. However, scarce data exist on IE perivalvular extension (PEE) in such patients. METHODS: This multicenter study included 579 patients who had the diagnosis of definite IE at a median of 171 (53-421) days following TAVR. PEE was defined as the presence of an intracardiac abscess, pseudoaneurysm, or fistula. RESULTS: A total of 105 patients (18.1%) were diagnosed with PEE (perivalvular abscess, pseudoaneurysm, fistula, or a combination in 87, 7, 7, and 4 patients, respectively). A history of chronic kidney disease (adjusted odds ratio [ORadj], 2.08; 95% confidence interval [CI]: 1.27-3.41; P = .003) and IE secondary to coagulase-negative staphylococci (ORadj, 2.71; 95% CI: 1.57-4.69; P < .001) were associated with an increased risk of PEE. Surgery was performed at index IE episode in 34 patients (32.4%) with PEE (vs 15.2% in patients without PEE, P < .001). In-hospital and 2-year mortality rates among PEE-IE patients were 36.5% and 69.4%, respectively. Factors independently associated with an increased mortality were the occurrence of other complications (stroke post-TAVR, acute renal failure, septic shock) and the lack of surgery at index IE hospitalization (padj < 0.05 for all). CONCLUSIONS: PEE occurred in about one-fifth of IE post-TAVR patients, with the presence of coagulase-negative staphylococci and chronic kidney disease determining an increased risk. Patients with PEE-IE exhibited high early and late mortality rates, and surgery during IE hospitalization seemed to be associated with better outcomes.

Effect of Timing of Staged Percutaneous Coronary Intervention on Clinical Outcomes in Patients With Acute Coronary Syndromes.

Background Complete revascularization reduces cardiovascular events in patients with acute coronary syndromes (ACSs) and multivessel disease. The optimal time point of non-target-vessel percutaneous coronary intervention (PCI) remains a matter of debate. The aim of this study was to investigate the impact of early (<4 weeks) versus late (≥4 weeks) staged PCI of non-target-vessels in patients with ACS scheduled for staged PCI after hospital discharge. Methods and Results All patients with ACS undergoing planned staged PCI from 2009 to 2017 at Bern University Hospital, Switzerland, were analyzed. Patients with cardiogenic shock, in-hospital staged PCI, staged cardiac surgery, and multiple staged PCIs were excluded. The primary end point was all-cause death, recurrent myocardial infarction and urgent premature non-target-vessel PCI. Of 8657 patients with ACS, staged revascularization was planned in 1764 patients, of whom 1432 patients fulfilled the eligibility criteria. At 1 year, there were no significant differences in the crude or adjusted rates of the primary end point (7.8% early versus 10.8% late, hazard ratio [HR], 0.72 [95% CI, 0.47-1.10], P=0.129; adjusted HR, 0.80 [95% CI, 0.50-1.28], P=0.346) and its individual components (all-cause death: 1.5% versus 2.9%, HR, 0.52 [95% CI, 0.20-1.33], P=0.170; adjusted HR, 0.62 [95% CI, 0.23-1.67], P=0.343; recurrent myocardial infarction: 4.2% versus 4.4%, HR, 0.97 [95% CI, 0.475-1.10], P=0.924; adjusted HR, 1.03 [95% CI, 0.53-2.01], P=0.935; non-target-vessel PCI, 3.9% versus 5.7%, HR, 0.97 [95% CI, 0.53-1.80], P=0.928; adjusted HR, 1.19 [95% CI, 0.61-2.34], P=0.609). Conclusions In this single-center cohort study of patients with ACS scheduled to undergo staged PCI after hospital discharge, early (<4 weeks) versus late (≥4 weeks) staged PCI was associated with a similar rate of major adverse cardiac events at 1 year follow-up. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT02241291.

Validation of high bleeding risk criteria and definition as proposed by the academic research consortium for high bleeding risk.

AIMS: To validate the set of clinical and biochemical criteria proposed by consensus by the Academic Research Consortium (ARC) for High Bleeding Risk (HBR) for the identification of HBR patients. These criteria were categorized into major and minor, if expected to carry in isolation, respectively, ≥4% and <4% Bleeding Academic Research Consortium (BARC) 3 or 5 bleeding risk within 1-year after percutaneous coronary intervention (PCI). High bleeding risk patients are those meeting at least 1 major or 2 minor criteria. METHODS AND RESULTS: All patients undergoing PCI at Bern University Hospital, between February 2009 and September 2018 were prospectively entered into the Bern PCI Registry (NCT02241291). Age, haemoglobin, platelet count, creatinine, and use of oral anticoagulation were prospectively collected, while the remaining HBR criteria except for planned surgery were retrospectively adjudicated. A total of 16 580 participants with complete ARC-HBR criteria were included. After assigning 1 point to each major and 0.5 point to each minor criterion, we observed for every 0.5 score increase a step-wise augmentation of BARC 3 or 5 bleeding rates at 1 year ranging from 1.90% among patients fulfilling no criterion, through 4.01%, 5.98%, 7.42%, 8.60%, 12.21%, 12.29%, and 17.64%. All major and five out of six minor criteria, conferred in isolation a risk for BARC 3 or 5 bleeding at 1 year exceeding 4% at the upper limit of the 95% confidence intervals. CONCLUSION: All major and the majority of minor ARC-HBR criteria identify in isolation patients at HBR.

Enoxaparin for primary thromboprophylaxis in ambulatory patients with coronavirus disease-2019 (the OVID study): a structured summary of a study protocol for a randomized controlled trial.

OBJECTIVES: The OVID study will demonstrate whether prophylactic-dose enoxaparin improves survival and reduces hospitalizations in symptomatic ambulatory patients aged 50 or older diagnosed with COVID-19, a novel viral disease characterized by severe systemic, pulmonary, and vessel inflammation and coagulation activation. TRIAL DESIGN: The OVID study is conducted as a multicentre open-label superiority randomised controlled trial. PARTICIPANTS: Inclusion Criteria 1. Signed patient informed consent after being fully informed about the study's background. 2. Patients aged 50 years or older with a positive test for SARS-CoV2 in the past 5 days and eligible for ambulatory treatment. 3. Presence of respiratory symptoms (i.e. cough, sore throat, or shortness of breath) or body temperature >37.5° C. 4. Ability of the patient to travel to the study centre by private transportation, performed either by an accompanying person from the same household or by the patient themselves 5. Ability to comply with standard hygiene requirements at the time of in-hospital visit, including a face mask and hand disinfectant. 6. Ability to walk from car to study centre or reach it by wheelchair transport with the help of an accompanying person from the same household also complying with standard hygiene requirements. 7. Ability to self-administer prefilled enoxaparin injections after instructions received at the study centre or availability of a person living with the patient to administer enoxaparin. Exclusion Criteria 1. Any acute or chronic condition posing an indication for anticoagulant treatment, e.g. atrial fibrillation, prior venous thromboembolism (VTE), acute confirmed symptomatic VTE, acute coronary syndrome. 2. Anticoagulant thromboprophylaxis deemed necessary in view of the patient's history, comorbidity or predisposing strong risk factors for thrombosis: a. Any of the following events occurring in the prior 30 days: fracture of lower limb, hospitalization for heart failure, hip/knee replacement, major trauma, spinal cord injury, stroke, b. previous VTE, c. histologically confirmed malignancy, which was diagnosed or treated (surgery, chemotherapy, radiotherapy) in the past 6 months, or recurrent, or metastatic, or inoperable. 3. Any clinically relevant bleeding (defined as bleeding requiring hospitalization, transfusion, surgical intervention, invasive procedures, occurring in a critical anatomical site, or causing disability) within 30 days prior to randomization or sign of acute bleeding. 4. Intracerebral bleeding at any time in the past or signs/symptoms consistent with acute intracranial haemorrhage. 5. Haemoglobin <8 g/dL and platelet count <50 x 109 cells/L confirmed by recent laboratory test (<90 days). 6. Subjects with any known coagulopathy or bleeding diathesis, including known significant liver disease associated with coagulopathy. 7. Severe renal insufficiency (baseline creatinine clearance <30 mL/min calculated using the Cockcroft-Gault formula) confirmed by recent laboratory test (<90 days). 8. Contraindications to enoxaparin therapy, including prior heparin-induced thrombocytopenia and known hypersensitivity. 9. Current use of dual antiplatelet therapy. 10. Participation in other interventional studies over the past 30 days. 11. Non-compliance or inability to adhere to treatment or lack of a family environment or support system for home treatment. 12. Cognitive impairment and/or inability to understand information provided in the study information. Patient enrolment will take place at seven Swiss centres, including five university hospitals and two large cantonal hospitals. INTERVENTION AND COMPARATOR: Patients randomized to the intervention group will receive subcutaneous enoxaparin at the recommended dose of 4,000 IU anti-Xa activity (40 mg/0.4 ml) once daily for 14 days. Patients randomized to the comparator group will receive no anticoagulation. MAIN OUTCOMES: Primary outcome: a composite of any hospitalization or all-cause death occurring within 30 days of randomization. SECONDARY OUTCOMES: (i) a composite of cardiovascular events, including deep vein thrombosis (including catheter-associated), pulmonary embolism, myocardial infarction/myocarditis, arterial ischemia including mesenteric and extremities, acute splanchnic vein thrombosis, or ischemic stroke within 14 days, 30 days, and 90 days of randomization; (ii) each component of the primary efficacy outcome, within 14 days, 30 days, and 90 days of randomization; (iii) net clinical benefit (accounting for the primary efficacy outcome, composite cardiovascular events, and major bleeding), within 14 days, 30 days, and 90 days of enrolment; (iv) primary efficacy outcome, within 14 days, and 90 days of enrolment; (v) disseminated intravascular coagulation (ISTH criteria, in-hospital diagnosis) within 14 days, 30 days, and 90 days of enrolment. RANDOMISATION: Patients will undergo block stratified randomization (by age: 50-70 vs. >70 years; and by study centre) with a randomization ratio of 1:1 with block sizes varying between 4 and 8. Randomization will be performed after the signature of the informed consent for participation and the verification of the eligibility criteria using the electronic data capture software (REDCAP, Vanderbilt University, v9.1.24). BLINDING (MASKING): In this open-label study, no blinding procedures will be used. NUMBERS TO BE RANDOMISED (SAMPLE SIZE): The sample size calculation is based on the parameters α = 0.05 (2-sided), power: 1-ß = 0.8, event rate in experimental group, pexp = 0.09 and event rate in control group, pcon = 0.15. The resulting total sample size is 920. To account for potential dropouts, the total sample size was fixed to 1000 with 500 patients in the intervention group and 500 in the control group. TRIAL STATUS: Protocol version 1.0, 14 April 2020. Protocol version 3.0, 18 May 2020 Recruiting start date: June 2020. Last Patient Last Visit: March 2021. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04400799 First Posted: May 26, 2020 Last Update Posted: July 16, 2020 FULL PROTOCOL: The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest in expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol.

Impact of Left Ventricular Outflow Tract Calcification on Procedural Outcomes After Transcatheter Aortic Valve Replacement.

OBJECTIVES: This study aimed to systematically assess the importance of left ventricular outflow tract (LVOT) calcification on procedural outcomes and device performances with contemporary transcatheter heart valve (THV) systems. BACKGROUND: LVOT calcification has been associated with adverse clinical outcomes after transcatheter aortic valve replacement (TAVR). However, the available evidence is limited to observational data with modest numbers and incomplete assessment of the effect of the different THV systems. METHODS: In a retrospective analysis of a prospective single-center registry, LVOT calcification was assessed in a semiquantitative fashion. Moderate or severe LVOT calcification was documented in the presence of 2 nodules of calcification, or 1 extending >5 mm in any direction, or covering >10 % of the perimeter of the LVOT. RESULTS: Among 1,635 patients undergoing TAVR between 2007 and 2018, moderate or severe LVOT calcification was found in 407 (24.9%). Patients with moderate or severe LVOT calcification had significantly higher incidences of annular rupture (2.3% vs. 0.2%; p < 0.001), bailout valve-in-valve implantation (2.9% vs. 0.8%; p = 0.004), and residual aortic regurgitation (11.1% vs. 6.3%; p = 0.002). Balloon-expandable valves conferred a higher risk of annular rupture in the presence of moderate or severe LVOT calcification (4.0% vs. 0.4%; p = 0.002) as compared with the other valve designs. There was no significant interaction of valve design or generation and LVOT calcification with regard to the occurrence of bailout valve-in-valve implantation and residual aortic regurgitation. CONCLUSIONS: Moderate or severe LVOT calcification confers increased risks of annular rupture, residual aortic regurgitation, and implantation of a second valve. The risk of residual aortic regurgitation is consistent across valve designs and generations. (SWISS TAVI Registry; NCT01368250).

Infective Endocarditis Following Transcatheter Aortic Valve Replacement: Comparison of Balloon- Versus Self-Expandable Valves.

BACKGROUND: No data exist about the characteristics of infective endocarditis (IE) post-transcatheter aortic valve replacement (TAVR) according to transcatheter valve type. We aimed to determine the incidence, clinical characteristics, and outcomes of patients with IE post-TAVR treated with balloon-expandable valve (BEV) versus self-expanding valve (SEV) systems. METHODS: Data from the multicenter Infectious Endocarditis After TAVR International Registry was used to compare IE patients with BEV versus SEV. RESULTS: A total of 245 patients with IE post-TAVR were included (SEV, 47%; BEV, 53%). The timing between TAVR and IE was similar between groups (SEV, 5.5 [1.2-15] months versus BEV, 5.3 [1.7-11.4] months; P=0.89). Enterococcal IE was more frequent in the SEV group (36.5% versus 15.4%; P<0.01), and vegetation location differed according to valve type (stent frame, SEV, 18.6%; BEV, 6.9%; P=0.01; valve leaflet, SEV, 23.9%; BEV, 38.5%; P=0.01). BEV recipients had a higher rate of stroke/systemic embolism (20.0% versus 8.7%, adjusted OR: 2.46, 95% CI: 1.04-5.82, P=0.04). Surgical explant of the transcatheter valve (SEV, 8.7%; BEV, 13.8%; P=0.21), and in-hospital death at the time of IE episode (SEV, 35.6%; BEV, 37.7%; P=0.74) were similar between groups. After a mean follow-up of 13±12 months, 59.1% and 54.6% of the SEV and BEV recipients, respectively, had died (P=0.66). CONCLUSIONS: The characteristics of IE post-TAVR, including microorganism type, vegetation location, and embolic complications but not early or late mortality, differed according to valve type. These results may help to guide the diagnosis and management of IE and inform future research studies in the field.