Learning Curve for Starting a Successful Single-Centre TAVR Programme with Multiple Devices: Early and Mid-Term Follow-Up.

Aims: We report 30-day, 1-year, and 3-year outcomes for a new TAVR programme that used five different transcatheter heart valve (THV) systems. Methods: From 2014 to 2020, 122 consecutive patients with severe aortic stenosis (AS) received TAVR based on the Heart Team decision. Outcomes were analysed for the whole study population and in addition the first 63 patients (Cohort A, 2014 to 2019) were compared to the last 59 patients (Cohort B, 2019 to 2020). Outcomes included VARC-2 definitions and device performance assessed via transthoracic echocardiography by independent high-volume investigators. Results: The mean patient age was 77.9 ± 6.1 years old, and 48 (39.3%) were male. The mean logistic Euroscore II was 4.2 ± 4.5, and the mean STS score was 6.9 ± 4.68. The systems used were as follows: Medtronic Corevalve Evolute R/PRO (82 patients-67.2%); Abbott Portico (13-10.6%); Boston Scientific Lotus (10-8.2%); Meril Myval (11-9%); and Boston Scientific Neo Accurate (6-5%). Access was transfemoral (95.9% of patients); surgical cut down (18% vs. percutaneous 77.8%); subclavian (n = 2); trans-axillary (n = 2); and direct aorta (n = 1). VARC-2 outcomes were as follows: device success rate 97.5%; stroke rate 1.6%; major vascular complication 3.3%; permanent pacemaker implantation 12.4%. At discharge, the incidences of grade I and II aortic regurgitation were 39.95 and 55.5%, respectively. At one year, all-cause mortality was 7.4% without admissions for valve-related dysfunction. The 3-year all-cause mortality and all-stroke rates were 22.9% and 4.1%, respectively. Between the 1-year and 3-year follow-ups, valve-related dysfunction was detected in three patients; one had THV system endocarditis that led to death. There was a remarkable but statistically non-significant decrease in mortality from Cohort A to Cohort B [four (6.3%) vs. one patient (1.7%), p = 0.195] and major vascular complications occurred at a significantly higher rate in the Cohort B [zero (0%) vs. four (6.8% patient, p = 0.036)]. Overall, we found that using multiple devices was safe and allowed for a learning team to achieve a high device success rate from the beginning (97.5%). Conclusions: TAVR with different THV systems showed acceptable early and mid-term outcomes for survival, technical success, and valve-related adverse events in high-risk patients with significant AS, even in the learning curve phase.

Single-Center Experience with the Balloon-Expandable Myval Transcatheter Aortic Valve System in Patients with Bicuspid Anatomy: Procedural and 30-Day Follow-Up.

Aims: To report our single-center data regarding the initial 52 consecutive patients with a bicuspid aortic valve who underwent a Transcatheter Aortic Valve Implantation (TAVI) procedure using the new balloon-expandable MYVAL system. The focus is on reporting procedural details and outcomes over the 30-day postoperative period. Methods: From December 2019 to July 2023, 52 consecutive patients underwent a TAVI procedure with bicuspid anatomy. All patients had moderate to-high surgical risk or were unsuitable for surgical aortic valve replacement based on the Heart Team's decision. Outcomes were analyzed according to the VARC-2 criteria. The results of bicuspid patients were compared to patients with tricuspid anatomy in the overall study group, and further analysis involved a comparison between 52 pairs after propensity score matching. The device performance was evaluated using transthoracic echocardiography. Data collection was allowed by the Local Ethical Committee. Results: The mean age was 71 ± 7.1 years, and 65.4% were male. The mean Euroscore II and STS score were 3.3 ± 3.2 and 5.2 ± 3.3, respectively. Baseline characteristics and echocardiographic parameters were well balanced even in the unmatched comparison. Procedures were significantly longer in the bicuspid group and resulted in a significantly higher ARI index. All relevant anatomic dimensions based on the CT scans were significantly higher in bicuspid anatomy, including a higher implantation angulation, a higher rate of horizontal aorta and a higher proportion of patients with aortopathy. In the unmatched bicuspid vs. tricuspid comparison, postprocedural outcomes were as follows: in-hospital mortality 0% vs. 1.4% (p = 0.394), device success 100% vs. 99.1% (p = 0.487), TIA 1.9% vs. 0% (p = 0.041), stroke 1.9% vs. 0.9% (p = 0.537), major vascular complication 3.8% vs. 2.3% (p = 0.530), permanent pacemaker implantation 34% vs. 30.4% (p = 0.429), and cardiac tamponade 0% vs. 0.5% (p = 0.624). In the propensity-matched bicuspid vs. tricuspid comparison, postprocedural outcomes were as follows: in-hospital mortality 0% vs. 0%, device success 100% vs. 100%, TIA 1.9% vs. 0% (p = 0.315), stroke 1.9% vs. 0.9% (p = 0.315), major vascular complication 3.8% vs. 0% (p = 0.475), permanent pacemaker implantation 34% vs. 24% (p = 0.274), and cardiac tamponade 0% vs. 0%. There was no annular rupture nor need for second valve or severe aortic regurgitation in both the unmatched and matched comparison. The peak and mean aortic gradients did not differ at discharge and at 30-day follow-up between the two groups regardless of whether the comparison was unmatched or matched. There were no paravalvular leakages (moderate or above) in the bicuspid patients. Intermediate and extra sizes of the Myval THV system used a significantly higher proportion in bicuspid anatomy with a significantly higher oversize percentage in tricuspid anatomy. Conclusions: The TAVI procedure using the Myval THV system in patients with significant aortic stenosis and bicuspid aortic valve anatomy is safe and effective. Hemodynamic parameters do not differ between tricuspid and bicuspid patients. However, the permanent pacemaker implantation rate is higher than expected; its relevance on long-term survival is controversial.

Inequalities in premature mortality from ischaemic heart disease in the WHO European region.

OBJECTIVES: Ischaemic heart disease (IHD) is one of the leading causes of premature mortality. Our aim was to analyse standardised premature mortality rates from IHD by geographical groups in the age group 45-59 years. METHODS: We performed a retrospective, quantitative analysis of age-standardized mortality rates from IHD between 1990-2014 per 100,000 population in Western European (WE: N = 17), Eastern European countries (EE: N = 10), and countries of the former Soviet Union (fSU: N = 15) within the European Region of the World Health Organisation (WHO) based on data retrieved from the WHO European Mortality Database. Descriptive statistics, time series analysis and statistical tests were used for the analyses (ANOVA, Kruskal-Wallis test, Mann-Whitney test, paired t-test). RESULTS: On average, age-standardized death rates (ASDR) from IHD per 100,000 population were the lowest in WE (men 1990: 143.67, 2014: 50.29; women 1990: 29.06, 2014: 9.89), and the highest in fSU (men 1990: 358.69, 2014: 253.25; women 1990: 99.78, 2014: 57.85). Between 1990 and 2014, all three groups experienced significant decrease in ASDR both in men and women (fSU: -29.39%, -42.02%; EE: -49.41%, -50.57%; WE: -64.99%, -65.97%, respectively) (p < 0.05). Between 1990 and 2004, ASDR decreased in WE in both sexes (p < 0.001), in EE among males (p = 0.032). Between 2004 and 2014, ASDR from IHD decreased significantly in both sexes in fSU and WE, in EE only among women (p < 0.05). CONCLUSIONS: During the whole period analysed, ischaemic heart disease mortality significantly decreased in both sexes in all the groups.

Optimal Renal Artery-Aorta Angulation Revealed by Flow Simulation.

INTRODUCTION: In the circulatory system, the vessel branching angle may have hemodynamic consequences. We hypothesized that there is a hemodynamically optimal range for the renal artery's branching angle. METHODS: Data on the posttransplant kinetics of estimated glomerular filtration rate (eGFR) were analyzed according to the donor and implant sides (right-to-right and left-to-right position; n = 46). The renal artery branching angle from the aorta of a randomly selected population was measured using an X-ray angiogram (n = 44). Computational fluid dynamics simulation was used to elucidate the hemodynamic effects of angulation. RESULTS AND DISCUSSION: Renal transplant patients receiving a right donor kidney to the right side showed faster adaptation and higher eGFR values than those receiving a left donor kidney to the right side (eGFR: 65 ± 7 vs. 56 ± 6 mL/min/1.73 m2; p < 0.01). The average branching angle on the left side was 78° and that on the right side was 66°. Simulation results showed that the pressure, volume flow, and velocity were relatively constant between 58° and 88°, indicating that this range is optimal for the kidneys. The turbulent kinetic energy does not change significantly between 58° and 78°. CONCLUSION: The results suggest that there is an optimal range for the renal artery's branching angle from the aorta where hemodynamic vulnerability caused by the degree of angulation is the lowest, which should be considered during kidney transplantations.

Short-term response of metabolic hormones to coronary artery bypass surgery.

PURPOSE: To explore the response pattern of plasma adipokine and ghrelin levels to coronary artery bypass graft (CABG) surgery in patients with (on-pump) and without (off-pump) cardiopulmonary bypass (CPB). MATERIAL/METHODS: Sixteen consecutive patients (age: 62 ± 10 years, male: 10) with obstructive coronary artery disease (CAD) who underwent elective CABG surgery with CPB and intraoperative GIK infusion were selected for on-pump group and 19 CAD patients (age: 63 ± 10 years, male: 16) were included in the off-pump group. Blood samples were taken before, during and after surgery. Intraoperative samples were withdrawn simultaneously for peripheral vein and sinus coronarius (SC). Plasma adipokine concentrations were measured by ELISA, those of ghrelin by RIA kits. RESULTS: In response to surgical intervention there was an early, transient fall in plasma levels of adiponectin (p<0.0001) and resistin (p=0.002) followed by an increase to approach their initial values. Plasma ghrelin also increased (p=0.045), this increase, however, was confined to the period of GIK supported CPB. Plasma insulin (p=0.003) and resistin (p=0.009) was significantly higher in the peripheral vein than in SC. The perioperative hormone profile of patients without CPB (off-pump) proved to be comparable to that of on-pump patients in spite of the insulin administration and greater oxidative and inflammatory stress. CONCLUSIONS: Adipose tissue-derived factors appear to mediate the metabolic and vascular changes that occur in patients with CABG surgery. Epicardial adipose tissue is unlikely to have major contribution to the development of CAD as adipokines are not elevated in SC independent of the mode of intervention.

Outcomes of patients receiving clopidogrel prior to cardiac surgery.

BACKGROUND: Clinical impact of the concomitant clopidogrel therapy on clinical outcomes in patients undergoing cardiac surgery is unclear. We aimed to pool and systematically analyze outcomes in clopidogrel-treated patients undergoing cardiac operations to achieve greater statistical power and to define precise effect-estimates. METHODS: PubMed and Central databases were searched for relevant studies published between January 2001 and May 2010. The main outcome measures were the rates of red blood cell (RBC) transfusion, reoperation, myocardial infarction and postoperative mortality. The outcome parameters were pooled with the random-effect model via generic-inverse variance-weighting. RESULTS: Twenty studies comprising a total number of 23,668 patients were analyzed. Pooled analysis revealed that the administration of clopidogrel had a higher risk for postoperative mortality (OR: 1.24; 95% CI: 1.03-1.49, p=0.03) that was consistent among studies. The rates of myocardial infarction were similar between groups. Clopidogrel-exposed patients were associated with a significantly higher rate of RBC transfusion (OR: 1.82; 95% CI: 1.40-2.37; p<0.00001) and reoperation (OR: 2.15; 95% CI: 1.38-3.34; p<0.00001), although there was a marked heterogeneity among studies. According to subgroup analysis the mortality and the rates of transfusions were higher in studies in which clopidogrel was not discontinued 5 days prior to surgery, while the higher risk for reoperation was only apparent in studies published before 2006. CONCLUSION: Meta-analysis of observational studies demonstrated that concomitant treatment with clopidogrel before cardiac surgery is associated with a significant risk of bleeding-related complications and with a higher mortality.

Prognostic significance of high on-clopidogrel platelet reactivity after percutaneous coronary intervention: systematic review and meta-analysis.

BACKGROUND: A growing number of observational studies suggest that high on-clopidogrel platelet reactivity (HPR) is associated with recurrent thrombotic events after percutaneous coronary intervention. We aimed to perform an updated systematic review and meta-analysis on the clinical relevance of HPR to summarize the available evidence and to define more precise effect estimates. METHODS: Relevant observational studies published between January 2003 and February 2010 were searched that presented intent-to-treat analyses on the clinical relevance of HPR measured with an adenosine diphosphate (ADP)-specific platelet function assay. The main outcome measures were cardiovascular (CV) death, definite/probable stent thrombosis (ST), nonfatal myocardial infarction (MI), and a composite end point of reported ischemic events. The outcome parameters were pooled with the random-effect model via generic inverse variance weighting. RESULTS: Twenty studies comprising a total number of 9,187 patients qualified. High on-clopidogrel platelet reactivity appeared to be a strong predictor of MI, ST, and the composite end point of reported ischemic events (odds ratios [95% CI]: 3.00 [2.26-3.99], 4.14 [2.74-6.25], and 4.95 [3.34-7.34], respectively; P < .00001 for all cases). According to the meta-analysis, patients with HPR had a 3.4-fold higher risk for CV death compared with patients with normal ADP reactivity (odds ratio 3.35, 95% CI 2.39-4.70, P < .00001). Although there were large differences in the methodology as well as in the definition of HPR between studies, the predicted risk for CV death, MI, or ST was not heterogeneous (I(2): 0%, 0%, and 12%, respectively; P = not significant for all cases). CONCLUSIONS: High on-clopidogrel platelet reactivity, measured by an ADP-specific platelet function assay, is a strong predictor of CV death, MI, and ST in patients after percutaneous coronary intervention.

Low platelet disaggregation predicts poor response to 150 mg clopidogrel in patients with elevated platelet reactivity.

Raising the maintenance dose of clopidogrel to 150 mg enhances platelet inhibition (PI) in patients with elevated platelet reactivity (EPR); however, large differences were observed between individuals in the extent of this benefit. We aimed to find clinical and platelet function variables that might predict the response to 150 mg clopidogrel in patients with EPR. ADP 5 microM-stimulated peak aggregation (Agg(max)), 6-minute late aggregation (Agg(late)) and 6-minute disaggregation (disAgg) were measured with light transmission aggregometry (LTA) in a consecutive cohort of 202 patients admitted for emergent or elective percutaneous coronary intervention (PCI) after receiving a 600-mg loading dose of clopidogrel. PI was assessed 12 to 18 hours after loading dose and 30 days after the intervention. EPR was defined as a Agg(max) value greater than 34%. From the first day of PCI, 85 patients with EPR received 150 mg clopidogrel for 30 days, while others with normal platelet reactivity (NPR) took 75 mg clopidogrel. Baseline clinical and LTA variables were analyzed in multivariable regression models. Administration of 150 mg clopidogrel enhanced PI and decreased the prevalence of EPR at 30 days compared to the peri-interventional period (Agg(max): 46.9 +/- 8.3 vs. 37.3 +/- 11.5; EPR: 100% vs. 62.4%; p < 0.001 in both cases); however, the achieved level of platelet reactivity was higher than patients with NPR (Agg(max): 20.6 +/- 8.1 vs. 25.3 +/- 10.8, p < 0.001). Multivariable logistic regression revealed low platelet disaggregation (odds ratio (OR): 12.49; 95% CI: 2.52-62.00; P = 0.002) and acute coronary syndrome (OR: 4.83; 95% CI: 1.54-15.09; P = 0.008) as independent predictors of EPR. The area under the receiver-operating-characteristic curve was 0.72 +/- 0.06 for disaggregation to predict NPR after 150 mg clopidogrel. The optimal disaggregation cut-off was 16.5% with a sensitivity of 94% and a specificity of 43%. Administering 150 mg maintenance dose of clopidogrel enhanced antiplatelet potency; however, more than half of the patients persisted with EPR. Acute coronary syndrome and low (<16.5%) platelet disaggregation are independent predictors of poor benefit from dose shift.