Extent of cardiac damage and hospitalization burden in patients undergoing transcatheter aortic valve replacement.

BACKGROUND: Cardiac damage has gained increasing attention as a valid prognostic marker of mortality after transcatheter aortic valve replacement (TAVR). However, studies investigating the possible association between cardiac damage and hospitalization burden in TAVR patients are lacking. AIMS: This study aimed to investigate the impact of baseline cardiac damage on the hospitalization burden before, during, and after TAVR in an all-comers population. METHODS: All consecutive patients who underwent TAVR between 2016 and 2020 were included. Electronic medical records of all patients were examined to validate cardiovascular (CV) and heart failure (HF) related hospitalizations from 6 months before to 1 year after TAVR. Baseline cardiac damage was defined according to the staging classification by Généreux et al. RESULTS: Among 1397 TAVR patients, 94 (6.7%) had stage 0, 368 (26.4%) stage 1, 736 (52.7%) stage 2, 115 (8.2%) stage 3, and 84 (6.0%) stage 4 cardiac damage. Patients with more advanced cardiac damage at baseline had more HF hospitalizations within 6 months before TAVR (p < 0.01) and with a longer length of stay (LoS) (p < 0.01). Regarding the index TAVR admission, there was no difference in procedure time (p = 0.26) or LoS (p = 0.18) between groups. Still, TAVR patients with more advanced baseline cardiac damage had a higher risk of CV and HF rehospitalization after TAVR (p < 0.05). CONCLUSIONS: Baseline cardiac damage in patients undergoing TAVR has an impact on the pre- and post-procedural cardiovascular hospitalization burden. However, the cardiac damage status does not affect the TAVR procedure time or index TAVR admission length of stay.

Comparative analysis of early postoperative results of transcatheter aortic valve implantation and surgical aortic valve replacement with a biological prosthesis.

OBJECTIVE: . Aim: The choice of aortic valve stenosis correction method is determined by a number of clinical and technical parameters. The task was to compare early postoperative outcomes in patients after correction of aortic valve stenosis using TAVI and surgical aortic valve replacement with a biological prosthesis. PATIENTS AND METHODS: Materials and Methods: This retrospective study analyzed the medical records of adult patients (18 years of age and older) who had transcatheter aortic valve implantation or surgical aortic valve replacement with a biological prosthesis at the State Institution "Heart Institute of the Ministry of Health" in the period from 2018 to 2022. RESULTS: Results: In 47 (47.5%) cases, TAVI was performed and in 52 (52.5%) cases, SAVR with a biological prosthesis was performed. Patients who underwent TAVI were significantly older (p=0.002) and had a higher EuroSCORE II operative risk score (p<0.001). In patients with TAVI, larger diameter aortic valve prostheses were significantly more often used compared with the SAVR group with biological prosthesis (27.5±2.74 vs. 22.5±1.84, p<0.001). The early postoperative period in patients with TAVI was characterized by an 11.4% (p=0.046) and 15.4% (p=0.006). The length of stay in the ICU (p=0.024), as well as the duration of hospitalization in general (p=0.005), was also significantly lower in patients with TAVI compared with patients with biological prosthesis SAVR. CONCLUSION: Conclusions: Despite the higher surgical risk of surgery according to EuroSCORE II, TAVI was characterized by a lower incidence of postoperative complications, with shorter duration of stay in ICU and hospitalization in general in comparison with patients undergoing SAVR with a biological prosthesis.

Identification of hub genes in calcific aortic valve disease.

Calcific aortic valve disease (CAVD) is a heart valve disorder characterized primarily by calcification of the aortic valve, resulting in stiffness and dysfunction of the valve. CAVD is prevalent among aging populations and is linked to factors such as hypertension, dyslipidemia, tobacco use, and genetic predisposition, and can result in becoming a growing economic and health burden. Once aortic valve calcification occurs, it will inevitably progress to aortic stenosis. At present, there are no medications available that have demonstrated effectiveness in managing or delaying the progression of the disease. In this study, we mined four publicly available microarray datasets (GSE12644 GSE51472, GSE77287, GSE233819) associated with CAVD from the GEO database with the aim of identifying hub genes associated with the occurrence of CAVD and searching for possible biological targets for the early prevention and diagnosis of CAVD. This study provides preliminary evidence for therapeutic and preventive targets for CAVD and may provide a solid foundation for subsequent biological studies.

Prevalence of moderate-severe aortic stenosis in patients with cardiac amyloidosis in a referral center.

BACKGROUND: Aortic stenosis (AS) is currently the most common valvular disease, with an estimated prevalence of over 4% in octogenarians. OBJECTIVE: To describe the prevalence of moderate-severe aortic stenosis (AS) in patients with wild type transthyretin amyloidosis (ATTRwt). Also, describe the clinical features, echocardiographic characteristics and clinical evolution. METHOD: Retrospective cohort of patients with diagnosis of ATTRwt, belonging to Hospital Italiano de Buenos Aires Institutional Amyloidosis Registry, from 30/11/2007 to 31/05/2021. Patients follow up was carried out through the institution clinical history. The prevalence of moderate-severe AE was estimated and presented as a percentage with its 95% confidence interval (95% CI). The characteristics were compared by groups according to whether or not they had moderate-severe AS. RESULTS: 104 patients with ATTRwt were included. Median follow up was 476 days [interquartile range: 192-749]. Moderate-severe AS prevalence at the ATTRwt time of diagnosis was 10.5% (n = 11; 95% CI: 5-18%). The median age of patients with AS moderate-severe at the time of diagnosis of ATTRwt was 86 years [78-91] and the male sex predominated (82%). Most of the patients had a history of heart failure (n = 8) and atrial fibrillation (n = 8) prior to the diagnosis of ATTRwt. Most of the patients were subclassified as low flow low gradient severe AS group (n = 7). Four patients underwent some intervention on the aortic valve. During follow-up, 5 patients (46%) were hospitalized for decompensated heart failure and 4 (36%) died. CONCLUSIONS: In our cohort, the coexistence of both pathologies had a similar prevalence as reported in the international literature. It was an elderly population with a high percentage of atrial fibrillation and history of heart failure. Most of the patients presented with severe AS with low flow low gradient.

ANTECEDENTES: La estenosis aórtica (EA) es actualmente la enfermedad valvular más frecuente, con una prevalencia estimada de más del 4 % en octogenarios. OBJETIVO: Describir la prevalencia de estenosis aórtica (EA) moderada-grave en pacientes con amiloidosis por transtiretina wild type (ATTRwt). Además, describir las características clínicas, ecocardiográficas y la evolución en este grupo de pacientes. MÉTODO: Estudio de cohorte retrospectiva de pacientes con diagnóstico de ATTRwt, pertenecientes al Registro Institucional de Amiloidosis del Hospital Italiano de Buenos Aires, en el periodo del 30/11/2007 al 31/05/2021. El seguimiento de los pacientes se realizó a través de la historia clínica electrónica de la institución. Se estimó la prevalencia de EA moderada-grave, que se presenta como porcentaje con su intervalo de confianza del 95% (IC 95%). Se compararon las características por grupos según tuvieran o no EA moderada-grave. RESULTADOS: Se incluyeron 104 pacientes con diagnóstico de ATTRwt. La mediana de seguimiento fue de 476 días [rango intercuartílico: 192-749]. La prevalencia de EA moderada-grave al momento del diagnóstico de ATTRwt fue del 10.5% (n = 11; IC95%: 5-18%). La mediana de edad de los pacientes con EA fue de 86 años [78-91] y predominó el sexo masculino (81.8%). La mayoría de los pacientes tenían el antecedente de insuficiencia cardiaca (n = 8) y fibrilación auricular (n = 8). Predominaron los pacientes con EA grave de bajo flujo y bajo gradiente (n = 7). Cuatro pacientes fueron sometidos a alguna intervención en la válvula aórtica. Durante el seguimiento, 5 pacientes (46%) tuvieron internaciones por insuficiencia cardiaca descompensada y 4 (36%) fallecieron. CONCLUSIONES: En nuestra cohorte, la coexistencia de ambas patologías tuvo una prevalencia similar a la reportada en la literatura internacional. Se trató de una población añosa con alto porcentaje de fibrilación auricular y antecedente de insuficiencia cardiaca. La mayoría presentaron EA grave de bajo flujo y bajo gradiente.

Prevalence and Outcomes of Patients With Discordant High-Gradient Aortic Stenosis.

BACKGROUND: Conflicting prognostic results have been reported in patients with discordant high-gradient aortic stenosis ([DHG-AS] the combination of a mean pressure gradient ≥40 mm Hg and an aortic valve area [AVA] >1 cm2). Moreover, existing studies only included selected patients without concomitant aortic regurgitation. OBJECTIVES: The authors assessed the prevalence and survival of patients presenting with DHG-AS in an unselected group of consecutive patients presenting to the echocardiography laboratory of a tertiary referral center. METHODS: A total of 3,547 adult patients with AVA ≤1.5 cm2 and peak aortic jet velocity ≥2.5 m/s or mean gradient ≥25 mm Hg who presented between 2005 and 2015 were included. Baseline clinical and echocardiographic data, and, when available, aortic valve calcium (AVC) score were collected in an institutional database, with subsequent retrospective analysis. The primary endpoint was all-cause mortality during follow-up. RESULTS: DHG-AS was observed in 163 patients (11.6% of patients with a high gradient). After adjustment for potential confounders, overall mortality rate of patients with DHG-AS was similar to that of patients with concordant severe aortic stenosis (HR: 0.98 [95% CI: 0.66-1.44]; P = 0.91), and patients with discordant low-gradient aortic stenosis (HR: 0.85 [95% CI: 0.58-1.26]; P = 0.42), and higher than concordant moderate aortic stenosis (HR: 0.54 [95% CI: 0.36-0.81]; P = 0.003). After adjustment for aortic velocities, aortic regurgitation had no significant impact on survival. AVC was higher than in patients with concordant moderate aortic stenosis and discordant low-gradient aortic stenosis, and not significantly different from that of concordant severe aortic stenosis. CONCLUSIONS: DHG-AS is not uncommon. Whereas AVA >1.0 cm2 is often seen as moderate aortic stenosis, a high-pressure gradient conveys a poor prognosis, whatever the AVA and the severity of concomitant aortic regurgitation.

Association of Bovine Arch Anatomy With Incident Stroke After Transcatheter Aortic Valve Replacement.

BACKGROUND: Acute ischemic stroke complicates 2% to 3% of transcatheter aortic valve replacements (TAVRs). This study aimed to identify the aortic anatomic correlates in patients after TAVR stroke. METHODS AND RESULTS: This is a single-center, retrospective study of patients who underwent TAVR at the Mayo Clinic between 2012 and 2022. The aortic arch morphology was determined via a manual review of the pre-TAVR computed tomography images. An "a priori" approach was used to select the covariates for the following: (1) the logistic regression model assessing the association between a bovine arch and periprocedural stroke (defined as stroke within 7 days after TAVR); and (2) the Cox proportional hazards regression model assessing the association between a bovine arch and long-term stroke after TAVR. A total of 2775 patients were included (59.6% men; 97.8% White race; mean±SD age, 79.3±8.4 years), of whom 495 (17.8%) had a bovine arch morphology. Fifty-seven patients (1.7%) experienced a periprocedural stroke. The incidence of acute stroke was significantly higher among patients with a bovine arch compared with those with a nonbovine arch (3.6% versus 1.7%; P=0.01). After adjustment, a bovine arch was independently associated with increased periprocedural strokes (adjusted odds ratio, 2.16 [95% CI, 1.22-3.83]). At a median follow-up of 2.7 years, the overall incidence of post-TAVR stroke was 6.0% and was significantly higher in patients with a bovine arch even after adjusting for potential confounders (10.5% versus 5.0%; adjusted hazard ratio, 2.11 [95% CI, 1.51-2.93]; P<0.001). CONCLUSIONS: A bovine arch anatomy is associated with a significantly higher risk of periprocedural and long-term stroke after TAVR.

Psoas Muscle Area as a Predictor of Transcatheter Aortic Valve Implantation Outcomes.

BACKGROUND: Frailty is a well-recognised predictor of outcomes after transcatheter aortic valve implantation (TAVI). Psoas muscle area (PMA) is a surrogate marker for sarcopaenia and is a validated assessment tool for frailty. The objective of this study was to examine frailty as a predictor of outcomes in TAVI patients and assess the prognostic usefulness of adding PMA to established frailty assessments. METHODS: Frailty assessments were performed on 220 consecutive patients undergoing TAVI. These assessments used four markers (serum albumin, handgrip strength, gait speed, and a cognitive assessment), which were combined to form a composite frailty score. Preprocedural computed tomography scans were used to calculate cross-sectional PMA for each patient. The primary outcomes were all-cause mortality at 1-year and post-procedure length of hospital stay. RESULTS: Frailty status, as defined by the composite frailty score, was independently predictive of length of hospital stay (p=0.001), but not predictive of 1-year mortality (p=0.161). Albumin (p=0.036) and 5-metre walk test (p=0.003) were independently predictive of 1-year mortality. The PMA, when adjusted for gender, and normalised according to body surface area, was not predictive of 1-year mortality. Normalised PMA was associated with increased post-procedure length of stay within the female population (p=0.031). CONCLUSIONS: A low PMA is associated with increased length of hospital stay in female TAVI patients but does not provide additional predictive value over traditional frailty scores. The PMA was not shown to correlate with TAVI-related complications or 1-year mortality.

Relationship between peak aortic jet velocity and progression of aortic stenosis in patients undergoing hemodialysis.

BACKGROUND: The natural history of aortic stenosis (AS) progression, especially before severe AS development, is not well documented. We aimed to investigate the time course of peak aortic jet velocity (Vmax) and AS progression risk according to baseline Vmax, particularly whether there is a Vmax threshold. METHODS: In a retrospective multicenter cohort study of patients on hemodialysis with aortic valve calcification, we investigated the time series of Vmax and the relationship between the baseline Vmax and progression to severe AS by analyzing longitudinal echocardiographic data. RESULTS: Among 758 included patients (mean age, 71 years; 65% male), patients with Vmax <1.5, 1.5-1.9, 2.0-2.4, 2.5-2.9, and 3.0-3.9 m/s were 395 (52%), 216 (29%), 85 (11%), 39 (5.1%), and 23 (3.0%), respectively. The Vmax slope was gradual (mean 0.05-0.07 m/s/year) at Vmax <2 m/s, but steeper (mean 0.13-0.21 m/s/year) at Vmax ≥2 m/s. During a median 3.2-year follow-up, 52 (6.9%) patients developed severe AS. While patients with Vmax <2 m/s rarely developed severe AS, the risk of those with Vmax ≥2 m/s increased remarkably with an increasing baseline Vmax; the adjusted incidence rates in patients with Vmax <1.5, 1.5-1.9, 2.0-2.4, 2.5-2.9, and 3.0-3.9 m/s were 0.59, 0.57, 4.25, 13.8, and 56.1 per 100 person-years, respectively; the adjusted hazard ratio per 0.2 m/s increase in the baseline Vmax was 1.49 (95% confidence interval: 1.32-1.68) when Vmax ≥2 m/s. CONCLUSIONS: The risk of progression to severe AS increased with the baseline Vmax primarily at ≥2 m/s; a Vmax threshold of 2 m/s was observed.

Impact of the COVID-19 Pandemic on Global TAVR Activity: The COVID-TAVI Study.

BACKGROUND: The COVID-19 pandemic adversely affected health care systems. Patients in need of transcatheter aortic valve replacement (TAVR) are especially susceptible to treatment delays. OBJECTIVES: This study sought to evaluate the impact of the COVID-19 pandemic on global TAVR activity. METHODS: This international registry reported monthly TAVR case volume in participating institutions prior to and during the COVID-19 pandemic (January 2018 to December 2021). Hospital-level information on public vs private, urban vs rural, and TAVR volume was collected, as was country-level information on socioeconomic status, COVID-19 incidence, and governmental public health responses. RESULTS: We included 130 centers from 61 countries, including 65,980 TAVR procedures. The first and second pandemic waves were associated with a significant reduction of 15% (P < 0.001) and 7% (P < 0.001) in monthly TAVR case volume, respectively, compared with the prepandemic period. The third pandemic wave was not associated with reduced TAVR activity. A greater reduction in TAVR activity was observed in Africa (-52%; P = 0.001), Central-South America (-33%; P < 0.001), and Asia (-29%; P < 0.001). Private hospitals (P = 0.005), urban areas (P = 0.011), low-volume centers (P = 0.002), countries with lower development (P < 0.001) and economic status (P < 0.001), higher COVID-19 incidence (P < 0.001), and more stringent public health restrictions (P < 0.001) experienced a greater reduction in TAVR activity. CONCLUSIONS: TAVR procedural volume declined substantially during the first and second waves of the COVID-19 pandemic, especially in Africa, Central-South America, and Asia. National socioeconomic status, COVID-19 incidence, and public health responses were associated with treatment delays. This information should inform public health policy in case of future global health crises.

Poor Oral Health Is Associated With Inflammation, Aortic Valve Calcification, and Brain Volume Among Forager-Farmers.

Poor oral health is associated with cardiovascular disease and dementia. Potential pathways include sepsis from oral bacteria, systemic inflammation, and nutritional deficiencies. However, in post-industrialized populations, links between oral health and chronic disease may be confounded because the lower socioeconomic exposome (poor diet, pollution, and low physical activity) often entails insufficient dental care. We assessed tooth loss, caries, and damaged teeth, in relation to cardiovascular and brain aging among the Tsimane, a subsistence population living a relatively traditional forager-horticulturalist lifestyle with poor dental health, but minimal cardiovascular disease and dementia. Dental health was assessed by a physician in 739 participants aged 40-92 years with cardiac and brain health measured by chest computed tomography (CT; n = 728) and brain CT (n = 605). A subset of 356 individuals aged 60+ were also assessed for dementia and mild cognitive impairment (n = 33 impaired). Tooth loss was highly prevalent, with 2.2 teeth lost per decade and a 2-fold greater loss in women. The number of teeth with exposed pulp was associated with higher inflammation, as measured by cytokine levels and white blood cell counts, and lower body mass index. Coronary artery calcium and thoracic aortic calcium were not associated with tooth loss or damaged teeth. However, aortic valve calcification and brain tissue loss were higher in those who had more teeth with exposed pulp. Overall, these results suggest that dental health is associated with indicators of chronic diseases in the absence of typical confounds, even in a population with low cardiovascular and dementia risk factors.

Associations of Lifelong Exercise Characteristics With Valvular Function and Aortic Diameters in Patients With a Bicuspid Aortic Valve.

BACKGROUND: The potential impact of exercise on valvular function and aortic diameters in patients with a bicuspid aortic valve remains unclear. Therefore, we assessed the association between lifelong exercise characteristics, valvular dysfunction, and aortic dilatation in patients with a bicuspid aortic valve. METHODS AND RESULTS: In this cross-sectional study, exercise volume (metabolic equivalent of task minutes per week), exercise intensity, and sport type were determined from the age of 12 years to participation using a validated questionnaire. Echocardiography was used to assess aortic stenosis or aortic regurgitation and to measure diameters at the sinuses of Valsalva and ascending aorta. Aortic dilatation was defined as a Z-score ≥2. Four hundred and seven patients (42±17 years, 60% men) were included, of which 133 were sedentary (<500 metabolic equivalent of task minutes per week), 94 active (500-1000 metabolic equivalent of task minutes per week), and 180 highly active (≥1000 metabolic equivalent of task minutes per week). Moderate-to-severe aortic stenosis or aortic regurgitation was present in 23.7% and 20.0%, respectively. Sinuses of Valsalva and ascending aorta diameters were 34.8±6.6 and 36.5±8.1 mm, whereas aortic dilatation was found in 21.6% and 53.4%, respectively. Exercise volume was not associated with valve dysfunction or aortic dilatation. Vigorous intensity and mixed sports were associated with a lower prevalence of aortic stenosis (adjusted odds ratios, 0.43 [0.20-0.94] and adjusted odds ratios, 0.47 [0.23-0.95]). Exercise intensity and sport type were not associated with aortic regurgitation and aortic dilatation. CONCLUSIONS: We found no deleterious associations between lifelong exercise characteristics, valvular dysfunction, and aortic dilatation in patients with a bicuspid aortic valve. Vigorous intensity and exercise in mixed sports were associated with a lower prevalence of moderate-to-severe aortic stenosis. These observations suggest that lifelong exercise does not appear to induce adverse cardiovascular effects in patients with a bicuspid aortic valve.

Limited Access to Aortic Valve Procedures in Socioeconomically Disadvantaged Areas.

BACKGROUND: To explore how differences in local socioeconomic deprivation impact access to aortic valve procedures and the treatment of aortic valve disease, in comparison to other open and minimally invasive surgical procedures. METHODS AND RESULTS: Procedure volume data were obtained from the Healthcare Cost and Utilization Project from 18 states from 2016 to 2019 and merged with area deprivation index data, an index of zip code-level socioeconomic distress. We estimate the relationship between local deprivation ranking and differences in volumes of aortic valve replacement, which include transcatheter aortic valve replacement (TAVR) and surgical aortic valve replacement (SAVR), versus coronary artery bypass graft surgery and laparoscopic colectomy (LC). All regressions control for state and year fixed effects and an array of zip code-level characteristics. TAVR procedures have increased over time across all zip codes. The rate of increase is negatively correlated with deprivation ranking, regardless of the higher share of hospitalizations per population in high deprivation areas. Distributional analysis further supports these findings, showing that lower area deprivation index areas account for a disproportionately large share of SAVR, TAVR, and LC procedures in our sample relative to their share of all hospitalizations in our sample. By comparison, the cumulative distribution of coronary artery bypass graft procedures was nearly identical to that of total hospitalizations, suggesting that this procedure is equitably distributed. Regressions show high area deprivation index areas have lower prevalence of SAVR (ß=-15.1%, [95% CI, -26.8 to -3.5]), TAVR (ß=-9.1%, [95% CI, -18.0 to -0.2]), and LC (ß=-19.9%, [95% CI, -35.4 to -4.4]), with no statistical difference in the prevalence of coronary artery bypass graft (ß=-2.5%, [95% CI, -12.7 to 7.6]), a widespread and commonly performed procedure. In the population aged ≥80 years, results show high area deprivation index areas have a lower prevalence of TAVR (ß=-11.9%, [95% CI, -18.7 to -5.2]) but not SAVR (ß=-0.8%, [95% CI, 8.1 to 6.3]), LC (ß=-3.5%, [95% CI, -13.4 to -6.4]), or coronary artery bypass graft (ß=5.2%, [95% CI, -1.1 to 1.1]). CONCLUSIONS: People living in high deprivation areas have less access to life-saving technologies, such as SAVR, and even moreso to device-intensive minimally invasive procedures such as TAVR and LC.

Prevalence of Aortic Valve Calcium and the Long-Term Risk of Incident Severe Aortic Stenosis.

BACKGROUND: Aortic valve calcification (AVC) is a principal mechanism underlying aortic stenosis (AS). OBJECTIVES: This study sought to determine the prevalence of AVC and its association with the long-term risk for severe AS. METHODS: Noncontrast cardiac computed tomography was performed among 6,814 participants free of known cardiovascular disease at MESA (Multi-Ethnic Study of Atherosclerosis) visit 1. AVC was quantified using the Agatston method, and normative age-, sex-, and race/ethnicity-specific AVC percentiles were derived. The adjudication of severe AS was performed via chart review of all hospital visits and supplemented with visit 6 echocardiographic data. The association between AVC and long-term incident severe AS was evaluated using multivariable Cox HRs. RESULTS: AVC was present in 913 participants (13.4%). The probability of AVC >0 and AVC scores increased with age and were generally highest among men and White participants. In general, the probability of AVC >0 among women was equivalent to men of the same race/ethnicity who were approximately 10 years younger. Incident adjudicated severe AS occurred in 84 participants over a median follow-up of 16.7 years. Higher AVC scores were exponentially associated with the absolute risk and relative risk of severe AS with adjusted HRs of 12.9 (95% CI: 5.6-29.7), 76.4 (95% CI: 34.3-170.2), and 380.9 (95% CI: 169.7-855.0) for AVC groups 1 to 99, 100 to 299, and ≥300 compared with AVC = 0. CONCLUSIONS: The probability of AVC >0 varied significantly by age, sex, and race/ethnicity. The risk of severe AS was exponentially higher with higher AVC scores, whereas AVC = 0 was associated with an extremely low long-term risk of severe AS. The measurement of AVC provides clinically relevant information to assess an individual's long-term risk for severe AS.

Plasma adiponectin levels and risk of heart failure, atrial fibrillation, aortic valve stenosis, and myocardial infarction: large-scale observational and Mendelian randomization evidence.

AIMS: Adiponectin may play an important protective role in heart failure and associated cardiovascular diseases. We hypothesized that plasma adiponectin is associated observationally and causally, genetically with risk of heart failure, atrial fibrillation, aortic valve stenosis, and myocardial infarction. METHODS AND RESULTS: In the Copenhagen General Population Study, we examined 30 045 individuals with plasma adiponectin measurements observationally and 96 903 individuals genetically in one-sample Mendelian randomization analyses using five genetic variants explaining 3% of the variation in plasma adiponectin. In the HERMES, UK Biobank, The Nord-Trøndelag Health Study (HUNT), deCODE, the Michigan Genomics Initiative (MGI), DiscovEHR, and the AFGen consortia, we performed two-sample Mendelian randomization analyses in up to 1 030 836 individuals using 12 genetic variants explaining 14% of the variation in plasma adiponectin.In observational analyses modelled linearly, a 1 unit log-transformed higher plasma adiponectin was associated with a hazard ratio of 1.51 (95% confidence interval: 1.37-1.66) for heart failure, 1.63 (1.50-1.78) for atrial fibrillation, 1.21 (1.03-1.41) for aortic valve stenosis, and 1.03 (0.93-1.14) for myocardial infarction; levels above the median were also associated with an increased risk of myocardial infarction, and non-linear U-shaped associations were more apparent for heart failure, aortic valve stenosis, and myocardial infarction in less-adjusted models. Corresponding genetic, causal risk ratios were 0.92 (0.65-1.29), 0.87 (0.68-1.12), 1.55 (0.87-2.76), and 0.93 (0.67-1.30) in one-sample Mendelian randomization analyses, and no significant associations were seen for non-linear one-sample Mendelian randomization analyses; corresponding causal risk ratios were 0.99 (0.89-1.09), 1.00 (0.92-1.08), 1.01 (0.79-1.28), and 0.99 (0.86-1.13) in two-sample Mendelian randomization analyses, respectively. CONCLUSION: Observationally, elevated plasma adiponectin was associated with an increased risk of heart failure, atrial fibrillation, aortic valve stenosis, and myocardial infarction. However, genetic evidence did not support causality for these associations.

Design and rationale of the evaluation of transcatheter aortic valve replacement compared to surveillance for patients with asymptomatic severe aortic stenosis: The EARLY TAVR trial.

BACKGROUND: For patients with asymptomatic, severe aortic stenosis (AS) and preserved left ventricular ejection fraction, current guidelines recommend clinical surveillance every 6 to 12 months. To date, no randomized trials have examined whether an early intervention with transcatheter aortic valve replacement (TAVR) will improve outcomes among these patients. STUDY DESIGN AND OBJECTIVES: EARLY TAVR is a prospective, randomized, controlled, and multicenter trial, with an event-based design. Asymptomatic severe AS patients (n = 900) are randomized 1:1 to either clinical surveillance or TAVR with the Edwards SAPIEN 3/SAPIEN 3 Ultra transcatheter heart valve. Patients are stratified by whether they are able to perform a treadmill stress test. The primary end point is death, stroke, or unplanned cardiovascular hospitalization. Patients who are asymptomatic but have a positive stress test will be followed in a registry and undergo aortic valve replacement as per current guidelines. CONCLUSIONS: EARLY TAVR is the largest randomized trial to date assessing the role of early intervention among patients with asymptomatic severe AS compared to clinical surveillance and the first to study the role of TAVR. TRIAL REGISTRATION NUMBER: NCT03042104.

Risk of Sinus Sequestration During Redo Transcatheter Aortic Valve Implantation: The Prevalence, Predictors, and Risk Stratification.

The number of patients who underwent transcatheter aortic valve implantation (TAVI) with the potential for reintervention is steadily increasing; however, there is a risk of sinus sequestration (SS) during a redo TAVI. The prevalence, predictors, and risk stratification of the risk for SS remain uncertain. We analyzed computed tomography acquired from 263 patients who underwent TAVI between 2021 and 2022: balloon-expandable valve (BEV) (71%) and self-expandable valve (SEV) (29%). Patients were considered at risk for SS if they met the following: (1) BEV frame > sinotubular junction (STJ) or SEV neocommissure greater than the STJ and (2) valve-to-STJ <2 mm. The risk of left, right, and any SS in 51%, 50%, and 65%, respectively, did not differ between BEV and SEV. The predictors of any SS were the height of the left and right coronary cusp (odds ratio [OR] 0.81 and 0.71, cutoff 18.6 and 19.2 mm, respectively) and STJ minus the annulus diameter (OR 0.65, cutoff 3.7 mm) in BEV, and STJ diameter (OR 0.47, cutoff 27.6 mm) in SEV. The number of predictors stratified the risk of any SS: low risk with BEV at 0 predictors (14% at risk of SS), intermediate risk at 1 predictor (65%), high risk at 2 or 3 predictors (81% and 95%), and low risk with SEV at 0 predictors (33%) versus high risk at 1 predictor (91%). In conclusion, 2/3 of patients who underwent TAVI were at risk of SS. The height of the coronary cusp and the STJ diameter were associated with and adequately stratified the risk of SS.

Transthyretin cardiac amyloidosis in patients with severe aortic stenosis undergoing transcatheter aortic valve replacement: experience of a single center.

BACKGROUND: Even if prevalent among patients with severe aortic stenosis (AS), the clinical suspicion for transthyretin cardiac amyloidosis (ATTR-CA) remains difficult in this subset. We report our single center experience on ATTR-CA detection among TAVR candidates to provide insights on the prevalence and clinical features of dual pathology as compared to lone AS. METHODS: Consecutive severe AS patients undergoing transcatheter aortic valve replacement (TAVR) evaluation at a single center were prospectively included. Those with suspected ATTR-CA based on clinical assessment underwent 99m Tc-3,3-diphosphono-1,2-propanodicarboxylic acid (DPD) bone scintigraphy. The RAISE score, a novel screening tool with high sensitivity for ATTR-CA in AS, was retrospectively calculated to rule-out ATTR-CA in the remaining patients. Patients were categorized as follow: "ATTR-CA+": patients with confirmed ATTR-CA at DPD bone scintigraphy; "ATTR-CA-": patients with negative DPD bone scintigraphy or a negative RAISE score; "ATTR-CA indeterminate": patients not undergoing ATTR-CA assessment with a positive RAISE score. The characteristics of ATTR-CA+ and ATTR-CA- patients were compared. RESULTS: Of 107 included patients, ATTR-CA suspicion was posed in 13 patients and confirmed in six. Patients were categorized as follow: 6 (5.6%) ATTR-CA+, 79 (73.8%) ATTR-CA-, 22 (20.6%) ATTR-CA indeterminate. Excluding ATTR-CA indeterminate patients, the prevalence of ATTR-CA was 7.1% (95% CI 2.6-14.7%). As compared to ATTR-CA - patients, ATTR-CA + patients were older, had higher procedural risk and more extensive myocardial and renal damage. They had higher left ventricle mass index and lower ECG voltages, translating into a lower voltage to mass ratio. Moreover, we describe for the first time bifascicular block as an ECG feature highly specific of patients with dual pathology (50.0% vs. 2.7%, P<0.001). Of note, pericardial effusion was rarely found in patients with lone AS (16.7% vs. 1.2%, P=0.027). No difference in procedural outcomes was observed between groups. CONCLUSIONS: Among severe AS patients, ATTR-CA is prevalent and presents with phenotypic features that may aid to differentiate it from lone AS. A clinical approach based on routine search of amyloidosis features might lead to selective DPD bone scintigraphy with a satisfactory positive predictive value.

Lipoprotein(a) and calcific aortic valve disease: current evidence and future directions.

PURPOSE OF REVIEW: Calcific aortic valve disease (CAVD), the most common cause of aortic stenosis (AS), is characterized by slowly progressive fibrocalcific remodelling of the valve cusps. Once symptomatic, severe AS is associated with poor survival unless surgical or transcatheter valve replacement is performed. Unfortunately, no pharmacological interventions have been demonstrated to alter the natural history of CAVD. Lipoprotein(a) [Lp(a)], a low-density lipoprotein-like particle, has been implicated in the pathophysiology of CAVD. RECENT FINDINGS: The mechanisms by which Lp(a) results in CAVD are not well understood. However, the oxidized phospholipids carried by Lp(a) are considered a crucial mediator of the disease process. An increasing number of studies demonstrate a causal association between plasma Lp(a) levels and frequency of AS and need for aortic valve replacement, which is independent of inflammation, as measured by plasma C-reactive protein levels. However, not all studies show an association between Lp(a) and increased progression of calcification in individuals with established CAVD. SUMMARY: Epidemiologic, genetic, and Mendelian randomization studies have collectively suggested that Lp(a) is a causal risk factor for CAVD. Whether Lp(a)-lowering can prevent initiation or slow progression of CAVD remains to be demonstrated.

Impact of stroke history on procedural cerebrovascular insult probability and long-term outcome after TAVI.

BACKGROUND: In TAVI procedural stroke is one of the most feared complications and for this reason also extensively studied. But there is a lack of data concerning the impact of previous stroke on procedural stroke and on long-term survival. The aim of this registry-based cohort study is to evaluate the prevalence of previous stroke in TAVI patients and its impact on procedural stroke risk as well as long-term outcome. METHODS: We included all patients treated with TAVI between January 2007 and December 2020 and investigated concerning previous stroke in their medical history. Among 958 patients, 55 patients had previous stroke and were included in the present analysis. RESULTS: The salient finding of the present study is that previous stroke is significantly associated with higher all-cause mortality and has established itself as a predictor for poor outcome after TAVI. This is also observed after adjusting for confounders like EuroSCORE II (European system for cardiac operative risk evaluation) and AF (atrial fibrillation) as one of the main underlying diseases for cerebrovascular insult (CVI). However, previous stroke is not associated with higher rates of procedural CVI. CONCLUSION: A history of stroke is significantly associated with higher all-cause mortality and has established itself as a predictor for poor outcome after TAVI without higher rates of procedural stroke.