Combined risk estimates of diabetes and coronary angiography-derived index of microcirculatory resistance in patients with non-ST elevation myocardial infarction.

BACKGROUND: Diabetes mellitus (DM) and coronary microvascular dysfunction (CMD) increase the risk of adverse cardiac events in patients with non-ST-segment elevation myocardial infarction (NSTEMI). This study aimed to evaluate the combined risk estimates of DM and CMD, assessed by the angiography-derived index of microcirculatory resistance (angio-IMR), in patients with NSTEMI. METHODS: A total of 2212 patients with NSTEMI who underwent successful percutaneous coronary intervention (PCI) were retrospectively enrolled from three centers. The primary outcome was a composite of cardiac death or readmission for heart failure at a 2-year follow-up. RESULTS: Post-PCI angio-IMR did not significantly differ between the DM group and the non-DM group (20.13 [17.91-22.70] vs. 20.19 [18.14-22.77], P = 0.530). DM patients exhibited a notably higher risk of cardiac death or readmission for heart failure at 2 years compared to non-DM patients (9.5% vs. 5.4%, P < 0.001). NSTEMI patients with both DM and CMD experienced the highest cumulative incidence of cardiac death or readmission for heart failure at 2 years (24.0%, P < 0.001). The combination of DM and CMD in NSTEMI patients were identified as the most powerful independent predictor for cardiac death or readmission for heart failure at 2 years (adjusted HR: 7.894, [95% CI, 4.251-14.659], p < 0.001). CONCLUSIONS: In patients with NSTEMI, the combination of DM and CMD is an independent predictor of cardiac death or readmission for heart failure. Angio-IMR could be used as an additional evaluation tool for the management of NSTEMI patients with DM. TRIAL REGISTRATION: URL: https://www. CLINICALTRIALS: gov ; Unique identifier: NCT05696379.

Comparison of Ticagrelor with Clopidogrel on Coronary Microvascular Dysfunction Following Acute Myocardial Infarction Using Angiography-Derived Index of Microcirculatory Resistance.

PURPOSE: This research aimed to assess the impact of ticagrelor and clopidogrel on coronary microvascular dysfunction (CMD) and prognosis following acute myocardial infarction (AMI), using the angiography-derived index of microcirculatory resistance (angio-IMR) as a non-invasive assessment tool. METHODS: In this retrospective study, angio-IMR was performed to evaluate CMD before and after dual antiplatelet therapy (DAPT) with either ticagrelor (90 mg twice daily, n = 184) or clopidogrel (75 mg once daily, n = 72). The primary endpoint is the improvement of CMD evaluated by angio-IMR (delta angio-IMR) following DAPT. Secondary endpoints included myocardial reinfarction and readmission for heart failure during 2-year follow-up. RESULTS: Compared with clopidogrel, ticagrelor exhibited a significantly higher delta angio-IMR [- 3.09 (5.14) versus - 1.99 (1.91), P = 0.008], indicating a superior improvement of CMD with ticagrelor treatment. Multivariate Cox regression indicated that ticagrelor treatment was related to a reduced risk of readmission for heart failure [8 (4.3) versus 9 (12.5), adjusted HR = 0.329; 95% CI = 0.116-0.934; P = 0.018] and myocardial reinfarction [7 (3.8) versus 8 (11.1), adjusted HR = 0.349; 95% CI = 0.125-0.975; P = 0.026]. Furthermore, ticagrelor treatment serves as an independent predictor of readmission for heart failure (HR = 0.322; 95% CI = 0.110-0.943; P = 0.039). CONCLUSION: The results of this study indicate a potential association between ticagrelor treatment and improved CMD, as well as a reduced risk of cardiovascular events, including myocardial reinfarction and readmission for heart failure in AMI patients. Further randomized controlled trials are necessary to confirm the potential benefits of ticagrelor on CMD and cardiovascular prognosis. This clinical trial was registered in www. CLINICALTRIALS: gov (NCT05978726).

Association between triglyceride-glucose index and all-cause mortality in patients underwent transcatheter aortic valve replacement.

BACKGROUNDS: The prognosis of the triglyceride-glucose (TyG) index, a validated surrogate marker for insulin resistance, in patients with severe aortic stenosis (AS) undergoing transcatheter aortic valve replacement (TAVR) remains unknown. METHODS: This study consecutively enrolled patients diagnosed with severe AS who underwent TAVR in a Chinese tertiary hospital from March 2013 to September 2023. Participants were stratified based on the TyG index cut-off value. Cox proportional hazards regression models were utilized to explore the association between the TyG index and all-cause mortality, including an assessment of interactions between the TyG index and various covariates on mortality outcomes. RESULTS: Among 1045 patients (mean age 74.7 years, 58.2% male), there was 134 all-cause mortality, resulting in a crude mortality rate of 64.3 per 1000 person-years. Adjusting for age, sex, body mass index, smoking, hypertension, diabetes mellitus, bicuspid aortic valve, atrial fibrillation, Society of Thoracic Surgeons (STS) score, and left ventricular ejection fraction, a per-unit increase in the TyG index was associated with a 41% higher all-cause mortality risk (HR 1.41, 95% CI 1.03-1.93, p = 0.030). Notably, the relationship between the TyG index and all-cause mortality was significantly modified by age (pinteraction = 0.027), sex (pinteraction = 0.007), hypertension (pinteraction = 0.030), and STS score (pinteraction = 0.002). CONCLUSIONS: A higher TyG index is significantly associated with an increased risk of all-cause mortality in AS patients after TAVR. These results underscore the importance of considering the TyG index in the prognostic evaluation of AS patients following TAVR.

Self-expanding transcatheter aortic valve replacement in patients with extremely horizontal aortas.

OBJECTIVES: To evaluate the feasibility of self-expanding transcatheter aortic valve replacement (TAVR) in patients with aortic stenosis and extremely horizontal aortas (aortic angulation ≥70°). BACKGROUND: As TAVR using a self-expanding prosthesis is an off-label treatment for patients with extremely horizontal aortas, these patients are often excluded from randomized controlled trials involving self-expanding TAVR. METHODS: This study enrolled 27 consecutive patients with extremely horizontal aortas who underwent self-expanding TAVR for severe aortic stenosis. RESULTS: The patients' average age was 76.4 years, with a median Society of Thoracic Surgeons score of 4.53%. The device success and 30-day mortality rates were 66.7% and 7.4%, respectively. The sinotubular junction (STJ) was significantly smaller in the device success group (p = 0.001). The receiver operating characteristic curve analysis found that the area under the curve was 0.907 (95% confidence interval: 0.790-1.000, p = 0.001), validating the association between STJ diameter and device success. An optimal cutoff of 33.6 mm was determined using the Youden index, with a sensitivity and specificity of 88.9% and 77.8%, respectively. The device success rate was significantly higher (93.3% vs. 33.3%, p = 0.003) in patients with STJ diameters ≤33.6 mm (n = 15). In the subgroup analyses, severe valve calcification (n = 9) was associated with a higher incidence of moderate or severe paravalvular leakage (44.0% vs. 0%, p = 0.008), while a higher rate of second valve implantation (60.0% vs. 9.1%, p = 0.030) was found in patients with less than moderate valve calcification (n = 5). CONCLUSION: Self-expanding TAVR could be suitable for patients with extremely horizontal aortas after careful preoperative evaluation.

Validation of a novel staging classification system based on the extent of cardiac damage among Chinese patients after transcatheter aortic valve replacement: A single-center retrospective study.

OBJECTIVES: We aimed to validate a novel staging system for aortic stenosis (AS) in a Chinese patient cohort undergoing transcatheter aortic valve replacement (TAVR), and to compare this classification system to the traditional Society of Thoracic Surgeons (STS) score for TAVR risk stratification. BACKGROUND: A novel staging system for AS based on the extent of cardiac damage upon echocardiography was recently proposed. METHODS: Patients were prospectively enrolled into the Transcatheter Aortic Valve Replacement Single Center Registry in Chinese Population and analyzed retrospectively following additional exclusion criteria. On the basis of echocardiographic findings of cardiac damage, patients were classified into five stages (0-4). RESULTS: A total of 427 patients were included in the current analysis. Forty-eight deaths occurred during a median follow-up of 730 days following TAVR. The staging system showed a statistically significant association between cardiac damage and all-cause mortality; advanced stages were associated with higher mortality. In a multivariate-adjusted Cox proportional hazards regression model, stage and STS scores served as risk factors for 2-year mortality. Each increment in the staging class was associated with an increased risk of mortality (hazard ratio, 1.275; 95% confidence interval [CI], 1.052-1.545). Receiver operating characteristic (ROC) curves were plotted for stage (area under the curve, 0.644; 95% CI, 0.562-0.725) and STS score (0.661; 0.573-0.749), and with no statistically significant differences between ROC curves (p = 0.920). CONCLUSIONS: We validated a novel staging system as a key risk factor for 2-year mortality in a Chinese TAVR patient cohort. Efficacy for risk stratification was comparable to the STS score.

Impact of repositioning on brain injury following transcatheter aortic valve replacement with a self-expanding valve.

Repositionable self-expanding valves allow for repositioning during deployment to achieve optimal valve placement. However, the risk of brain injury associated with repositioning, as detected by diffusion-weighted magnetic resonance imaging (DW-MRI), is unknown. Consecutive patients undergoing transcatheter aortic valve replacement (TAVR) with repositionable self-expanding valves and receiving DW-MRI before and within 7 days post-TAVR procedure were included. The primary outcomes were incidence, number, total volume, and volume per lesion of the cerebral ischemic lesion in DW-MRI after TAVR. Univariate and multivariate logistic regression assessed the association between repositioning and bigger total lesion volume (> 1 cm3 or > 0.5 cm3). Negative binomial regressions were performed to explore the association between repositioning and number of lesions. A propensity score matching was performed to adjust the potential confounders. Moreover, inverse probability of treatment weighted regression model with nonstabilized weights was used as sensitivity analysis. Among 243 included patients, repositioning was performed in 116 (47.7%) patients. The incidence of overt stroke (1.7% vs. 1.6%, p = 0.927) and silent stroke (86.2% vs. 85.8%, p = 0.932) were comparable between two groups. However, the number of new lesions (5.0 [2.0-9.0] vs. 3.0 [2.0-6.0], p = 0.048), and total lesion volume (275.0 [90.0-947.5] mm3 vs. 180.0 [50.0-440.0] mm3, p = 0.022) were significantly higher in the repositioned group. Moreover, the proportion of patients with lesion size greater than 0.5 cm3 was higher in the repositioned group (37.9% vs. 22.0%, p = 0.007). The similar results were observed after propensity score matching. In both multivariate regression model and sensitivity analysis, the repositioning was the independent predictor of number of lesions and bigger total lesion volume after TAVR. The utilization of the repositioning feature may increase the number and volume of silent brain infarcts in DW-MRI in patients who underwent TAVR. (Transcatheter Aortic Valve Replacement Single Center Registry in Chinese Population [TORCH]; NCT02803294).

Prognostic Value of Coronary Angiography-Derived Index of Microcirculatory Resistance in Non-ST-Segment Elevation Myocardial Infarction Patients.

BACKGROUND: The index of microcirculatory resistance is a reliable measure for evaluating coronary microvasculature, but its prognostic value in patients with non-ST-segment elevation myocardial infarction (NSTEMI) remains unclear. OBJECTIVES: This study aimed to evaluate the prognostic impact of postpercutaneous coronary intervention (PCI) angiography-derived index of microcirculatory resistance (angio-IMR) in patients with NSTEMI. METHODS: The culprit vessel's angio-IMR was measured after PCI in 2,212 NSTEMI patients at 3 sites. The primary endpoint was 2-year major adverse cardiac events (MACEs), defined as a composite of cardiac death, readmission for heart failure, myocardial reinfarction, and target vessel revascularization. RESULTS: The mean post-PCI angio-IMR was 20.63 ± 4.17 in NSTEMI patients. A total of 206 patients were categorized as the high post-PCI angio-IMR group according to maximally selected log-rank statistics. Patients with angio-IMR >25 showed a higher rate of MACEs than those with angio-IMR ≤25 (32.52% vs 9.37%; P < 0.001). Post-PCI angio-IMR >25 was an independent predictor of MACEs (HR: 4.230; 95% CI: 3.151-5.679; P < 0.001) and showed incremental prognostic value compared with conventional risk factors (AUC: 0.774 vs 0.716; P < 0.001; net reclassification index: 0.317; P < 0.001; integrated discrimination improvement: 0.075; P < 0.001). CONCLUSIONS: In patients undergoing PCI for NSTEMI, an increased post-PCI angio-IMR is associated with a higher risk of MACEs. The addition of post-PCI angio-IMR into conventional risk factors significantly improves the ability to reclassify patients and estimate the risk of MACEs. (Angiograph-Derived Index of Microcirculatory Resistance in Patients With Acute Myocardial Infarction; NCT05696379).

Wearable smartwatch monitoring arrhythmias for patients who at high risk of pacemaker implantation after transcatheter aortic valve replacement.

Graphical Abstract.

Technical Success after Transcatheter Aortic Valve Replacement for Bicuspid versus Tricuspid Aortic Stenosis.

Background: Comparative data of the Valve Academic Research Consortium (VARC-3)-defined technical success between bicuspid versus tricuspid aortic stenosis (AS) remain lacking. Aims: We sought to compare the technical success and other clinical outcomes between patients with bicuspid and tricuspid AS receiving transcatheter aortic valve replacement. Methods: A registration-based analysis was performed for 402 patients (211 and 191 cases of bicuspid and tricuspid AS, respectively). The primary outcome was VARC-3-defined technical success. Additional analysis was performed to assess outcomes for up to one year between the two groups. Results: Bicuspid AS patients tended to be younger (74 years vs. 77 years; p < 0.001) with a lower Society of Thoracic Surgeons score (4.4% vs. 5.4%; p = 0.003). Bicuspid AS patients showed a lower prevalence of hypertension and peripheral vascular diseases. Technical failure was encountered in 17.7% of these patients, driven primarily by the high incidence of second valve implantation. The technical success rates were comparable between the bicuspid and tricuspid AS groups (82.5% vs. 82.2%, p = 0.944). Chronic kidney disease (CKD) and larger sinotubular junctional diameter (STJ) were identified as predictors of technical failure, whereas CKD, impaired left ventricular ejection fraction (LVEF), along with larger STJ, were predictors of cardiac technical failure. Technical failure was associated with an increased risk of all-cause mortality at 30 days and 1 year, as evidenced by the Cox multivariable analysis. Conclusions: No significant differences were observed in the technical success rates and most clinical outcomes between the bicuspid and tricuspid AS groups. Technical failure conferred an increased risk for both 30-day and 1-year all-cause mortalities.

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Considering the surgical risk stratification for patients with severe calcific aortic stenosis (AS), transcatheter aortic valve replacement (TAVR) is a reliable alternative to surgical aortic valve replacement (SAVR) (Fan et al., 2020, 2021; Lee et al., 2021). Despite the favorable clinical benefits of TAVR, stroke remains a dreaded perioperative complication (Auffret et al., 2016; Kapadia et al., 2016; Kleiman et al., 2016; Huded et al., 2019). Ischemic overt stroke, identified in 1.4% to 4.3% of patients in TAVR clinical practice, has been associated with prolonged disability and increased mortality (Auffret et al., 2016; Kapadia et al., 2016; Levi et al., 2022). The prevalence of hyperintensity cerebral ischemic lesions detected by diffusion-weighted magnetic resonance imaging (DW-MRI) was reported to be about 80%, which is associated with impaired neurocognitive function and vascular dementia (Vermeer et al., 2003; Barber et al., 2008; Kahlert et al., 2010).

Self-Expanding Transcatheter Aortic Valve Replacement for Pure Aortic Regurgitation With Extremely Horizontal Aorta: A Case Series.

Transcatheter aortic valve replacement (TAVR) is not the preferred therapy for pure aortic regurgitation (AR). Extremely horizontal aorta (aorta root angle ≥70°) is regarded as an "off-label" use in self-expanding TAVR. This case series enrolled 7 consecutive pure AR patients who had extremely horizontal aorta and underwent self-expanding TAVR from the TORCH registry. To the best of our knowledge, this is the first study to report successful self-expanding TAVR for pure AR with extremely horizontal aorta, revealing the feasibility of both transapical and transfemoral TAVR in this challenging population.

Causal Associations Between Circulating Adipokines and Cardiovascular Disease: A Mendelian Randomization Study.

CONTEXT: Observational studies have suggested associations between adipokines and cardiovascular disease (CVD), but the roles of certain adipokines remain controversial, and these associations have not yet been ascertained causally. OBJECTIVE: To investigate whether circulating adipokines causally affect the risk of CVD using 2-sample Mendelian randomization (MR). METHODS: Independent genetic variants strongly associated with adiponectin, resistin, chemerin, and retinol binding protein 4 (RBP4) were selected from public genome-wide association studies. Summary-level statistics for CVD, including coronary artery disease (CAD), myocardial infarction, atrial fibrillation (AF), heart failure (HF), and stroke and its subtypes were collected. The inverse-variance weighted and Wald ratio methods were used for the MR estimates. The MR pleiotropy residual sum and outlier, weighted median, MR-Egger, leave-one-out analysis, MR Steiger, and colocalization analyses were used in the sensitivity analysis. RESULTS: Genetically predicted resistin levels were positively associated with AF risk (odds ratio [OR] 1.09; 95% confidence interval [CI], 1.04-1.13; P = 4.1 × 10-5), which was attenuated to null after adjusting for blood pressure. We observed suggestive associations between higher genetically predicted chemerin levels and an increased risk of CAD (OR 1.27; 95% CI, 1.01-1.60; P = 0.040), higher genetically predicted RBP4 levels and an increased risk of HF (OR 1.14; 95% CI, 1.02-1.27; P = 0.024). There was no causal association between genetically predicted adiponectin levels and CVD risk. CONCLUSIONS: Our findings reveal the causal association between resistin and AF, probably acting through blood pressure, and suggest potential causal associations between chemerin and CAD, RBP4, and HF.

Emergently Alteration of Procedural Strategy During Transcatheter Aortic Valve Replacement to Prevent Coronary Occlusion: A Case Report.

Background: Coronary occlusion is an uncommon but fatal complication of transcatheter aortic valve replacement (TAVR) with a poor prognosis. Case Presentation: A patient with symptomatic severe bicuspid aortic valve stenosis was admitted to a high-volume center specializing in transfemoral TAVR with self-expanding valves. No anatomical risk factors of coronary occlusion were identified on pre-procedural computed tomography analysis. The patient was scheduled for a transfemoral TAVR with a self-expanding valve. Balloon pre-dilatation prior to prosthesis implantation was routinely used for assessing the supra-annular structure and assessing the risk of coronary occlusion. Immediately after the tubular balloon inflation, fluoroscopy revealed that the right coronary artery was not visible, and the flow in the left coronary artery was reduced. The patient would be at high-risk of coronary occlusion if a long stent self-expanding valve was implanted. Therefore, our heart team decided to suspend the ongoing procedure. A transapical TAVR with a 23 mm J-valve was performed 3 days later. The prosthesis was deployed at a proper position without blocking the coronary ostia and the final fluoroscopy showed normal flow in bilateral coronary arteries with the same filling as preoperatively. Discussion: Our successful case highlights the importance of a comprehensive assessment of coronary risk and a thorough understanding of the TAVR procedure for the heart team. A short-stent prosthesis is feasible for patients at high risk of coronary occlusion. Most importantly TAVR should be called off even if the catheter has been introduced when an extremely high risk of coronary obstruction is identified during the procedure and no solution can be found.

Cerebral Ischemic Lesions after Transcatheter Aortic Valve Implantation in Patients with Non-Calcific Aortic Stenosis.

Evidence for transcatheter aortic valve implantation (TAVI) is scarce among patients with non-calcific aortic stenosis, and it is not known whether aortic valve calcification is associated with new cerebral ischemic lesions (CILs) that are detected by diffusion-weighted magnetic resonance imaging. So, our study enrolled 328 patients who underwent transfemoral TAVI using a self-expanding valve between December 2016 and June 2021 from the TORCH registry (NCT02803294). A total of 34 patients were finally confirmed as non-calcific AS and the remaining 294 patients were included in the calcific AS group. Incidence of new CILs (70.6% vs. 85.7%, p = 0.022), number of lesions (2.0 vs. 3.0, p = 0.010), and lesions volume (105.0 mm3 vs. 200.0 mm3, p = 0.047) was significantly lower in the non-calcific AS group. However, the maximum and average lesion volumes were comparable between two groups. Non-calcific AS was associated with lower risk for developing new CILs by univariate logistic regression analysis [Odds ratio (OR): 0.040, 95% confident interval (CI): 0.18-0.90, p = 0.026] and multivariate analysis (OR: 0.031, 95% CI: 0.13-0.76, p = 0.010). In summary, non-calcific AS patients had a lower risk of developing new cerebral ischemic infarction after TAVI compared to calcific AS patients. However, new ischemic lesions were still found in over 70% of patients.

Three-year outcomes of transcatheter aortic valve implantation for bicuspid versus tricuspid aortic stenosis.

BACKGROUND: Transcatheter aortic valve implantation (TAVI) might be a feasible treatment option for more patients with bicuspid aortic valve (BAV) stenosis. However, long-term follow-up data in this population are scarce. AIMS: The aim of this study was to evaluate three-year outcomes after TAVI in patients with BAV. METHODS: A total of 246 consecutive patients who underwent TAVI at a single centre in China between March 2013 and February 2018 were enrolled in this study. Clinical outcomes, health status and echocardiography were followed and recorded for three years. RESULTS: Among 109 (44.3%) BAV patients, 61.5% were Type 0 and 36.7% were Type 1 BAV patients. BAV patients were younger (75 vs 77 years, p=0.041) and had a lower Society of Thoracic Surgeons (STS) score (5.09 vs 6.00, p=0.026) compared to tricuspid aortic valve (TAV) patients. There were no differences in three-year survival rates between bicuspid and tricuspid patients (87.1% vs 79.5%, log-rank p=0.126). Multivariate Cox regression analysis adjusting for confounding factors revealed a similar risk of all-cause mortality in the BAV population (hazard ratio [HR] 0.86, 95% confidence interval [CI]: 0.44-1.70, p=0.666). Except for the rate of permanent pacemaker implantation that was lower in BAV patients (11.9% vs 21.9%, p=0.041), the incidence of other clinical adverse events was comparable between the two groups. Both BAV and TAV patients showed an obvious improvement in valve haemodynamics, which was sustained for three years. In addition, similar left ventricular reverse remodelling was found during follow-up. CONCLUSIONS: BAV patients showed similar satisfactory three-year clinical outcomes, persistent valve haemodynamics improvement, and obvious cardiac reverse remodelling after TAVI compared to TAV patients.