Complex percutaneous coronary intervention in patients unable to undergo coronary artery bypass grafting during the COVID-19 pandemic: insights from the UK-ReVasc Registry.

OBJECTIVES: Cardiac surgery for coronary artery disease was dramatically reduced during the first wave of the COVID-19 pandemic. Many patients with disease ordinarily treated with coronary artery bypass grafting (CABG) instead underwent percutaneous coronary intervention (PCI). We sought to describe 12-month outcomes following PCI in patients who would typically have undergone CABG. METHODS: Between March 1 and July 31, 2020, patients who received revascularization with PCI when CABG would have been the primary choice of revascularization were enrolled in the prospective, multicenter UK-ReVasc Registry. We evaluated the following major adverse cardiovascular events at 12 months: all-cause mortality, myocardial infarction, repeat revascularization, stroke, major bleeding, and stent thrombosis. RESULTS: A total of 215 patients were enrolled across 45 PCI centers in the United Kingdom. Twelve-month follow up data were obtained for 97% of the cases. There were 9 deaths (4.3%), 5 myocardial infarctions (2.4%), 12 repeat revascularizations (5.7%), 1 stroke (0.5%), 3 major bleeds (1.4%), and no cases of stent thrombosis. No difference in the primary endpoint was observed between patients who received complete vs incomplete revascularization (residual SYNTAX score £ 8 vs > 8) (P = .22). CONCLUSIONS: In patients with patterns of coronary disease in whom CABG would have been the primary therapeutic choice outside of the pandemic, PCI was associated with acceptable outcomes at 12 months of follow-up. Contemporary randomized trials that compare PCI to CABG in such patient cohorts may be warranted.

Transcatheter aortic valve-in-valve implantation within stentless landing zones: Procedural insights from a single-center experience.

BACKGROUND: Valve-in-valve (VIV) transcatheter aortic valve implantation (TAVI) is a less invasive therapeutic option compared with redo surgical valve replacement for high-risk patients. Relative to procedures within stented surgical valves, VIV-TAVI within stentless valves is associated with a higher complication rate due to challenging underlying anatomy and absence of fluoroscopic landmarks. AIMS: We share a single-center experience with VIV-TAVI in stentless valves, discussing our procedural insights and associated outcomes. METHODS: Our institutional database was queried, and 25 patients who had undergone VIV-TAVI within a stentless bioprosthesis, homograft, or valve-sparing aortic root replacement between 2013 and 2022 were found. Outcome endpoints were based on the Valve Academic Research Consortium-3 criteria. RESULTS: The mean age of the cohort was 69.5 ± 13.6 years. VIV implantation was performed within a homograft in 11 patients, a stentless bioprothesis in 10 patients, and a valve-sparing aortic root replacement in 4 patients. Nineteen (76%) balloon-expandable valves, 5 (20%) self-expanding valves, and one mechanically-expandable (4%) valve were implanted with 100% procedural success, with no instances of significant paravalvular leak, coronary occlusion, or device embolization. There was one (4%) in-hospitality mortality after an emergency procedure; one (4%) patient experienced a transient ischemic attack; and two (8%) patients required permanent pacemaker implantation. The median length of hospital stay was 2 days. After a median follow-up time of 16.5 months, valve function was acceptable in all patients with available data. CONCLUSION: VIV-TAVI within stentless valves can be safely performed with methodical procedural technique and can provide clinical benefit in patients at high reoperation risk.

Bacteremia following different oral procedures: Systematic review and meta-analysis.

To evaluate the timing, duration and incidence of bacteremia following invasive dental procedures (IDPs) or activities of daily living (ADL). Eight databases were searched for randomized (RCTs) and nonrandomized controlled trials (nRCTs) evaluating bacteremia before and after IDPs or ADL in healthy individuals. The risk of bias was assessed by RoB 2.0 and ROBINS-I. For the meta-analysis, the primary outcomes were the timing and duration of bacteremia. The secondary outcome was the incidence of bacteremia, measuring the proportion of patients with bacteremia within 5 min after the end of the procedure compared with baseline. We included 64 nRCTs and 25 RCTs. Peak bacteremia occurred within 5 min after the procedure and then decreased over time. Dental extractions showed the highest incidence of bacteremia (62%-66%), followed by scaling and root planing (SRP) (44%-36%) and oral health procedures (OHP) (e.g., dental prophylaxis and dental probing without SRP) (27%-28%). Other ADL (flossing and chewing) (16%) and toothbrushing (8%-26%) resulted in bacteremia as well. The majority of studies had some concerns RCTs or moderate risk of bias nRCTs. Dental extractions, SRP and OHP, are associated with the highest frequency of bacteremia. Toothbrushing, flossing, and chewing also caused bacteremia in lower frequency.

Impact of Right Ventricle-Pulmonary Artery Coupling on Clinical Outcomes in the PARTNER 3 Trial.

BACKGROUND: Physiologic right ventricle-pulmonary artery (RV-PA) coupling may be impaired in patients with aortic stenosis (AS). OBJECTIVES: This study aimed to assess the incidence and prognostic significance of impaired RV-PA coupling in low-risk patients with symptomatic severe AS undergoing transcatheter aortic valve replacement or surgical aortic valve replacement. METHODS: RV-PA coupling was measured by transthoracic echocardiography as the ratio of tricuspid annular plane systolic excursion (TAPSE) to pulmonary artery systolic pressure (PASP) in patients in the PARTNER (Placement of Aortic Transcatheter Valve) 3 trial. The primary endpoint was the composite of all-cause mortality, stroke, and rehospitalization at the 2-year follow-up. RESULTS: Among 570 low-risk patients included in the analysis, RV-PA uncoupling was defined by a TAPSE/PASP ratio ≤ 0.55 mm/mm Hg. At baseline, 222 of 570 (38.9%) patients had RV-PA uncoupling. At 2 years, patients with baseline RV-PA uncoupling had an increased incidence of the primary endpoint (19.1% vs 9.9%, P = 0.002), all-cause mortality (5.9% vs 0.6%, P < 0.001), cardiovascular mortality (4.1% vs 0.6%, P = 0.003), and rehospitalization (13.5% vs 7.3%, P = 0.018). On multivariable analysis, baseline RV-PA uncoupling remained an independent predictor of the primary endpoint at 2 years (HR: 1.92; 95% CI: 1.04-3.57; P = 0.038). CONCLUSIONS: In patients with symptomatic severe AS at low surgical risk undergoing transcatheter aortic valve replacement or surgical aortic valve replacement, baseline RV-PA uncoupling defined by TAPSE/PASP ≤ 0.55 mm Hg was associated with adverse clinical outcomes at 2 years, including all-cause mortality, cardiovascular mortality, and rehospitalization.

Subclinical Leaflet Thrombosis and Anticoagulation After Transcatheter Aortic Valve Replacement: A Review.

Importance: Subclinical leaflet thrombosis affects approximately 15% of patients after transcatheter aortic valve replacement (TAVR). The pathophysiology and clinical significance of leaflet thrombosis remain incompletely understood. Defining the optimal management strategy in patients who are asymptomatic, including the role for oral anticoagulation (OAC), is a key challenge for the field. Observations: Three recent randomized trials have evaluated the role of OAC in patients after TAVR. These studies have confirmed prior observational data suggesting that OAC is effective at prevention of subclinical leaflet thrombosis. Overall, however, OAC does not lead to a clinical benefit over the period studied, and in some patients may be harmful owing to bleeding risk. Conclusions and Relevance: Strategies for identification of patients in whom the benefit of OAC outweighs the risks are required for optimization of long-term outcome after TAVR. This requires clearer insights into the mechanisms of asymptomatic leaflet thrombosis, its clinical significance, and patient-specific risks of bleeding and structural valve degeneration.

Risk of infective endocarditis after surgical and transcatheter aortic valve replacement.

OBJECTIVE: To define the incidence and risk factors for infective endocarditis (IE) following surgical aortic valve replacement (SAVR) and transcatheter aortic valve implantation (TAVI). METHODS: All patients who underwent first SAVR or TAVI in England between 2007 and 2016 were identified from the NICOR databases. Hospital admissions with a primary diagnosis of IE were identified by linkage with the NHS Hospital Episode Statistics database. Approval was obtained from the NHS Research Ethics Committee. RESULTS: 2057 of 91 962 patients undergoing SAVR developed IE over a median follow-up of 53.9 months-an overall incidence of 4.81 [95% CI 4.61 to 5.03] per 1000 person-years. Correspondingly, 140 of 14 195 patients undergoing TAVI developed IE over a median follow-up of 24.5 months-an overall incidence of 3.57 [95% CI 3.00 to 4.21] per 1000 person-years. The cumulative incidence of IE at 60 months was higher after SAVR than after TAVI (2.4% [95% CI 2.3 to 2.5] vs 1.5% [95% CI 1.3 to 1.8], HR 1.60, p<0.001). Across the entire cohort, SAVR remained an independent predictor of IE after multivariable adjustment. Risk factors for IE included younger age, male sex, atrial fibrillation, and dialysis. CONCLUSIONS: IE is a rare complication of SAVR and TAVI. In our population, the incidence of IE was higher after SAVR than after TAVI.

Outcomes following PCI in CABG candidates during the COVID-19 pandemic: The prospective multicentre UK-ReVasc registry.

OBJECTIVES: To describe outcomes following percutaneous coronary intervention (PCI) in patients who would usually have undergone coronary artery bypass grafting (CABG). BACKGROUND: In the United Kingdom, cardiac surgery for coronary artery disease (CAD) was dramatically reduced during the first wave of the COVID-19 pandemic. Many patients with "surgical disease" instead underwent PCI. METHODS: Between 1 March 2020 and 31 July 2020, 215 patients with recognized "surgical" CAD who underwent PCI were enrolled in the prospective UK-ReVasc Registry (ReVR). 30-day major cardiovascular event outcomes were collected. Findings in ReVR patients were directly compared to reference PCI and isolated CABG pre-COVID-19 data from British Cardiovascular Intervention Society (BCIS) and National Cardiac Audit Programme (NCAP) databases. RESULTS: ReVR patients had higher incidence of diabetes (34.4% vs 26.4%, P = .008), multi-vessel disease with left main stem disease (51.4% vs 3.0%, P < .001) and left anterior descending artery involvement (94.8% vs 67.2%, P < .001) compared to BCIS data. SYNTAX Score in ReVR was high (mean 28.0). Increased use of transradial access (93.3% vs 88.6%, P = .03), intracoronary imaging (43.6% vs 14.4%, P < .001) and calcium modification (23.6% vs 3.5%, P < .001) was observed. No difference in in-hospital mortality was demonstrated compared to PCI and CABG data (ReVR 1.4% vs BCIS 0.7%, P = .19; vs NCAP 1.0%, P = .48). Inpatient stay was half compared to CABG (3.0 vs 6.0 days). Low-event rates in ReVR were maintained to 30-day follow-up. CONCLUSIONS: PCI undertaken using contemporary techniques produces excellent short-term results in patients who would be otherwise CABG candidates. Longer-term follow-up is essential to determine whether these outcomes are maintained over time.

Real-World Experience With the SAPIEN 3 Ultra Transcatheter Heart Valve: A Propensity-Matched Analysis From the United States.

[Figure: see text].

Suprasternal Versus Transfemoral Access for Transcatheter Aortic Valve Replacement: Insights From a Propensity Score Matched Analysis.

Background Suprasternal access is an alternative access strategy for transcatheter aortic valve replacement (TAVR) where the innominate artery is cannulated from an incision above the sternal notch. To date, suprasternal access has never been compared with transfemoral TAVR. Thus, we sought to assess safety, feasibility, and early clinical outcomes between suprasternal and transfemoral access for patients undergoing TAVR. Methods and Results We evaluated patients from 2 institutional prospective, observational registries containing 1348 patients. Patients were selected in a 2:1 ratio (transfemoral:suprasternal) on the basis of propensity score matching. The primary outcome was in-hospital mortality, and secondary outcomes included the incidence of ischemic stroke, major bleeding, vascular injury, left bundle-branch block, and permanent pacemaker implantation at 30-day follow-up. Propensity score matching identified 89 patients undergoing suprasternal TAVR and 159 patients undergoing transfemoral TAVR suitable for analysis. There was no significant difference between suprasternal TAVR and transfemoral TAVR with respect to in-hospital mortality (1.1% versus 0.6%; odds ratio [OR], 1.80; 95% CI, 0.11-29.06; P=0.680). No patients in either cohort suffered an ischemic stroke. The incidence of major bleeding (2.2% versus 2.5%; OR, 0.89; 95% CI, 0.16-4.96; P=0.895) and vascular injury (1.1% versus 1.9%; OR, 0.59; 95% CI, 0.06-5.77; P=0.651) did not differ significantly. The frequency of left bundle-branch block (9.4% versus 15.8%; OR, 0.56; 95% CI, 0.24-1.30; P=0.177) and permanent pacemaker implantation (11.2% versus 5.9%; OR, 2.01; 95% CI, 0.75-5.45; P=0.169) were not statistically significantly different. Conclusions Suprasternal TAVR was safe and achieved promising short-term clinical outcomes when compared with transfemoral TAVR. Future studies seeking to identify the optimal alternative access site should evaluate suprasternal TAVR access alongside other substitutes for transfemoral TAVR.

Hyperglycemia Induces Trained Immunity in Macrophages and Their Precursors and Promotes Atherosclerosis.

BACKGROUND: Cardiovascular risk in diabetes remains elevated despite glucose-lowering therapies. We hypothesized that hyperglycemia induces trained immunity in macrophages, promoting persistent proatherogenic characteristics. METHODS: Bone marrow-derived macrophages from control mice and mice with diabetes were grown in physiological glucose (5 mmol/L) and subjected to RNA sequencing (n=6), assay for transposase accessible chromatin sequencing (n=6), and chromatin immunoprecipitation sequencing (n=6) for determination of hyperglycemia-induced trained immunity. Bone marrow transplantation from mice with (n=9) or without (n=6) diabetes into (normoglycemic) Ldlr-/- mice was used to assess its functional significance in vivo. Evidence of hyperglycemia-induced trained immunity was sought in human peripheral blood mononuclear cells from patients with diabetes (n=8) compared with control subjects (n=16) and in human atherosclerotic plaque macrophages excised by laser capture microdissection. RESULTS: In macrophages, high extracellular glucose promoted proinflammatory gene expression and proatherogenic functional characteristics through glycolysis-dependent mechanisms. Bone marrow-derived macrophages from diabetic mice retained these characteristics, even when cultured in physiological glucose, indicating hyperglycemia-induced trained immunity. Bone marrow transplantation from diabetic mice into (normoglycemic) Ldlr-/- mice increased aortic root atherosclerosis, confirming a disease-relevant and persistent form of trained innate immunity. Integrated assay for transposase accessible chromatin, chromatin immunoprecipitation, and RNA sequencing analyses of hematopoietic stem cells and bone marrow-derived macrophages revealed a proinflammatory priming effect in diabetes. The pattern of open chromatin implicated transcription factor Runt-related transcription factor 1 (Runx1). Similarly, transcriptomes of atherosclerotic plaque macrophages and peripheral leukocytes in patients with type 2 diabetes were enriched for Runx1 targets, consistent with a potential role in human disease. Pharmacological inhibition of Runx1 in vitro inhibited the trained phenotype. CONCLUSIONS: Hyperglycemia-induced trained immunity may explain why targeting elevated glucose is ineffective in reducing macrovascular risk in diabetes and suggests new targets for disease prevention and therapy.

Community prevalence, mechanisms and outcome of mitral or tricuspid regurgitation.

OBJECTIVE: The study aims were (1) to identify the community prevalence of moderate or greater mitral or tricuspid regurgitation (MR/TR), (2) to compare subjects identified by population screening with those with known valvular heart disease (VHD), (3) to understand the mechanisms of MR/TR and (4) to assess the rate of valve intervention and long-term outcome. METHODS: Adults aged ≥65 years registered at seven family medicine practices in Oxfordshire, UK were screened for inclusion (n=9504). Subjects with known VHD were identified from hospital records and those without VHD invited to undergo transthoracic echocardiography (TTE) within the Oxford Valvular Heart Disease Population Study (OxVALVE). The study population ultimately comprised 4755 subjects. The severity and aetiology of MR and TR were assessed by integrated comprehensive TTE assessment. RESULTS: The prevalence of moderate or greater MR and TR was 3.5% (95% CI 3.1 to 3.8) and 2.6% (95% CI 2.3 to 2.9), respectively. Primary MR was the most common aetiology (124/203, 61.1%). Almost half of cases were newly diagnosed by screening: MR 98/203 (48.3%), TR 69/155 (44.5%). Subjects diagnosed by screening were less symptomatic, more likely to have primary MR and had a lower incidence of aortic valve disease. Surgical intervention was undertaken in six subjects (2.4%) over a median follow-up of 64 months. Five-year survival was 79.8% in subjects with isolated MR, 84.8% in those with isolated TR, and 59.4% in those with combined MR and TR (p=0.0005). CONCLUSIONS: Moderate or greater MR/TR is common, age-dependent and is underdiagnosed. Current rates of valve intervention are extremely low.

Tissue-resident macrophages regulate lymphatic vessel growth and patterning in the developing heart.

Macrophages are components of the innate immune system with key roles in tissue inflammation and repair. It is now evident that macrophages also support organogenesis, but few studies have characterized their identity, ontogeny and function during heart development. Here, we show that the distribution and prevalence of resident macrophages in the subepicardial compartment of the developing heart coincides with the emergence of new lymphatics, and that macrophages interact closely with the nascent lymphatic capillaries. Consequently, global macrophage deficiency led to extensive vessel disruption, with mutant hearts exhibiting shortened and mis-patterned lymphatics. The origin of cardiac macrophages was linked to the yolk sac and foetal liver. Moreover, the Cx3cr1+ myeloid lineage was found to play essential functions in the remodelling of the lymphatic endothelium. Mechanistically, macrophage hyaluronan was required for lymphatic sprouting by mediating direct macrophage-lymphatic endothelial cell interactions. Together, these findings reveal insight into the role of macrophages as indispensable mediators of lymphatic growth during the development of the mammalian cardiac vasculature.

Safety and Operational Efficiency of Restructuring and Redeploying a Transcatheter Aortic Valve Replacement Service During the COVID-19 Pandemic: The Oxford Experience.

BACKGROUND: The risk of nosocomial COVID-19 infection for vulnerable aortic stenosis patients and intensive care resource utilization has led to cardiac surgery deferral. Untreated severe symptomatic aortic stenosis has a dismal prognosis. TAVR offers an attractive alternative to surgery as it is not reliant on intensive care resources. We set out to explore the safety and operational efficiency of restructuring a TAVR service and redeploying it to a new non-surgical site during the COVID-19 pandemic. METHODS: The institutional prospective service database was retrospectively interrogated for the first 50 consecutive elective TAVR cases prior to and after our institution's operational adaptations for the COVID-19 pandemic. Our endpoints were VARC-2 defined procedural complications, 30-day mortality or re-admission and service efficiency metrics. RESULTS: The profile of patients undergoing TAVR during the pandemic was similar to patients undergoing TAVR prior to the pandemic with the exception of a lower mean age (79 vs 82 years, p < 0.01) and median EuroScore II (3.1% vs 4.6%, p = 0.01). The service restructuring and redeployment contributed to the pandemic-mandated operational efficiency with a reduction in the distribution of pre-admission hospital visits (3 vs 3 visits, p < 0.001) and the time taken from TAVR clinic to procedure (26 vs 77 days, p < 0.0001) when compared to the pre-COVID-19 service. No statistically significant difference was noted in peri-procedural complications and 30-day outcomes, while post-operative length of stay was significantly reduced (2 vs 3 days, p < 0.0001) when compared to pre-COVID-19 practice. CONCLUSIONS: TAVR service restructuring and redeployment to align with pandemic-mandated healthcare resource rationalization is safe and feasible.

Global Burden of Cardiovascular Diseases and Risk Factors, 1990-2019: Update From the GBD 2019 Study.

Cardiovascular diseases (CVDs), principally ischemic heart disease (IHD) and stroke, are the leading cause of global mortality and a major contributor to disability. This paper reviews the magnitude of total CVD burden, including 13 underlying causes of cardiovascular death and 9 related risk factors, using estimates from the Global Burden of Disease (GBD) Study 2019. GBD, an ongoing multinational collaboration to provide comparable and consistent estimates of population health over time, used all available population-level data sources on incidence, prevalence, case fatality, mortality, and health risks to produce estimates for 204 countries and territories from 1990 to 2019. Prevalent cases of total CVD nearly doubled from 271 million (95% uncertainty interval [UI]: 257 to 285 million) in 1990 to 523 million (95% UI: 497 to 550 million) in 2019, and the number of CVD deaths steadily increased from 12.1 million (95% UI:11.4 to 12.6 million) in 1990, reaching 18.6 million (95% UI: 17.1 to 19.7 million) in 2019. The global trends for disability-adjusted life years (DALYs) and years of life lost also increased significantly, and years lived with disability doubled from 17.7 million (95% UI: 12.9 to 22.5 million) to 34.4 million (95% UI:24.9 to 43.6 million) over that period. The total number of DALYs due to IHD has risen steadily since 1990, reaching 182 million (95% UI: 170 to 194 million) DALYs, 9.14 million (95% UI: 8.40 to 9.74 million) deaths in the year 2019, and 197 million (95% UI: 178 to 220 million) prevalent cases of IHD in 2019. The total number of DALYs due to stroke has risen steadily since 1990, reaching 143 million (95% UI: 133 to 153 million) DALYs, 6.55 million (95% UI: 6.00 to 7.02 million) deaths in the year 2019, and 101 million (95% UI: 93.2 to 111 million) prevalent cases of stroke in 2019. Cardiovascular diseases remain the leading cause of disease burden in the world. CVD burden continues its decades-long rise for almost all countries outside high-income countries, and alarmingly, the age-standardized rate of CVD has begun to rise in some locations where it was previously declining in high-income countries. There is an urgent need to focus on implementing existing cost-effective policies and interventions if the world is to meet the targets for Sustainable Development Goal 3 and achieve a 30% reduction in premature mortality due to noncommunicable diseases.

Over 15 years: the advancement of transcatheter aortic valve replacement.

The management of aortic stenosis has been revolutionized by transcatheter aortic valve replacement (TAVR). Initially only undertaken in patients at prohibitive or high surgical risk, as the evidence base and indications have expanded, TAVR is now approved and undertaken in patients at all risk levels. Evolution of valve technology, delivery systems and pathways for patient work-up have been rapid, with associated reductions in the complication profile, particularly vascular complications. Challenges remain as TAVR continues to advance, however, specifically achieving further reduction in paravalvular regurgitation, the requirement for permanent pacemaker implantation, and balancing the risks of thrombosis and bleeding. In this review, we outline the historical advances leading to contemporary TAVR practice, and discuss the future trajectory.

How to prevent infective endocarditis in 2020? Practical issues.

The incidence of infective endocarditis (IE) continues to rise in many populations and is typically accompanied by a shift to healthcare­associated staphylococcal species. Despite efforts with aggressive antibiotic therapy and increasing rates of surgical intervention, little progress has been made to reduce mortality. Disease prevention is therefore a crucial part of limiting its effects. Prevention should target each point in the pathogenic triad of IE: initiating bacteremia, adhesion to substrate, and proliferation of pathogenic species. Preventative strategies should focus on at­risk patients undergoing high­risk procedures, and these patients and procedures can now be identified by quantitative risk estimates. The attendant risk resulting from a procedure must then be placed in the perspective of the day­to­day risk, and the resulting balance can inform the benefit of prophylactic antibiotics. Implantable devices are a major risk factor for IE, and novel coatings and designs may be effective in risk reduction. Guidelines differ worldwide and a consensus has yet to be reached on who should receive pre­ and periprocedural antibiotics.