Ticagrelor vs Clopidogrel for Complex Percutaneous Coronary Intervention in Chronic Coronary Syndrome.

BACKGROUND: Whether ticagrelor in chronic coronary syndrome patients undergoing complex percutaneous coronary intervention (PCI) can prevent cardiovascular events is unknown. OBJECTIVES: The authors sought to evaluate outcomes of complex PCI and the efficacy of ticagrelor vs clopidogrel in stable patients randomized in the ALPHEUS (Assessment of Loading with the P2Y12 inhibitor ticagrelor or clopidogrel to Halt ischemic Events in patients Undergoing elective coronary Stenting) trial. METHODS: All PCI procedures were blindly reviewed and classified as complex if they had at least 1 of the following criteria: stent length >60 mm, 2-stent bifurcation, left main, bypass graft, chronic total occlusion, use of atherectomy or guiding catheter extensions, multiwire technique, multiple stents. The primary endpoint was a composite of type 4a or b myocardial infarction (MI) and major myocardial injury during the 48 hours after PCI. We compared the event rates according to the presence or not of complex PCI criteria and evaluated the interaction with ticagrelor or clopidogrel. RESULTS: Among the 1,866 patients randomized, 910 PCI (48.3%) were classified as complex PCI. The primary endpoint was more frequent in complex PCI (45.6% vs 26.6%; P < 0.001) driven by higher rates of type 4 MI and angiographic complications (12.2% vs 4.8 %; P < 0.001 and 19.3% vs 8.6%; P < 0.05, respectively). The composite of death, MI, and stroke at 48 hours (12.7% vs 5.1 %; P < 0.05) and at 30 days (13.4% vs 5.3%; P < 0.05) was more frequent in complex PCI. No interaction was found between PCI complexity and the randomized treatment for the primary endpoint (Pinteraction = 0.47) nor the secondary endpoints. CONCLUSIONS: In chronic coronary syndrome, patients undergoing a complex PCI have higher rates of periprocedural and cardiovascular events that are not reduced by ticagrelor as compared with clopidogrel.

Outcomes of patients with myocardial infarction and cardiogenic shock treated with culprit vessel-only versus multivessel primary PCI.

INTRODUCTION AND OBJECTIVES: Multivessel primary percutaneous coronary intervention (pPCI) is still often used in patients with ST-elevation myocardial infarction (STEMI) and cardiogenic shock (CS). The study aimed to compare the characteristics and prognosis of patients with CS-STEMI and multivessel coronary disease (MVD) treated with culprit vessel-only pPCI or multivessel-pPCI during the initial procedure. MATERIAL AND METHODS: From 2016 to 2020, 23,703 primary PCI patients with STEMI were included in a national all-comers registry of cardiovascular interventions. Of them, 1,213 (5.1%) patients had CS and MVD at admission to the hospital. Initially, 921 (75.9%) patients were treated with culprit vessel (CV)-pPCI and 292 (24.1%) with multivessel (MV)-pPCI. RESULTS: Patients with 3-vessel disease and left main disease had a higher probability of being treated with MV-pPCI than patients with 2-vessel disease and patients without left main disease (28.5% vs. 18.6%; p < 0.001 and 37.7% vs. 20.6%; p < 0.001). Intra-aortic balloon pump, extracorporeal membrane oxygenation (ECMO), and other mechanical circulatory support systems were more often used in patients with MV-pPCI. Thirty (30)-day and 1-year all-cause mortality rates were similar in the CV-pPCI and MV-pPCI groups (odds ratio, 1.01; 95% confidence interval [CI] 0.77 to 1.32; p = 0.937 and 1.1; 95% CI 0.84 to 1.44; p = 0.477). The presence of 3-vessel disease and the use of ECMO were the strongest adjusted predictors of 30-day and 1-year mortality. CONCLUSIONS: Our data from an extensive all-comers registry suggests that selective use of MV-pPCI does not increase the all-cause mortality rate in patients with CS-STEMI and MVD compared to CV-pPCI.

Optimal timing of influenza vaccination among patients with acute myocardial infarction - Findings from the IAMI trial.

Influenza vaccination reduces the risk of adverse cardiovascular events.The IAMI trial randomly assigned 2571 patients with acute myocardial infarction (AMI) to receive influenza vaccine or saline placebo during their index hospital admission. It was conducted at 30 centers in 8 countries from October 1, 2016 to March 1, 2020. In this post-hoc exploratory sub-study, we compare the trial outcomes in patients receiving early season vaccination (n = 1188) and late season vaccination (n = 1344).The primary endpoint wasthe composite of all-cause death, myocardial infarction (MI), or stent thrombosis at 12 months. Thecumulative incidence of the primary and key secondary endpoints by randomized treatment and early or late vaccination was estimated using the Kaplan-Meier method. In the early vaccinated group, the primary composite endpoint occurred in 36 participants (6.0%) assigned to influenza vaccine and 49 (8.4%) assigned to placebo (HR 0.69; 95% CI 0.45 to 1.07), compared to 31 participants (4.7%) assigned to influenza vaccine and 42 (6.2%) assigned to placebo (HR 0.74; 95% CI 0.47 to 1.18) in the late vaccinated group (P = 0.848 for interaction on HR scale at 1 year). We observed similar estimates for the key secondary endpoints of all-cause death and CV death. There was no statistically significant difference in vaccine effectiveness against adverse cardiovascular events by timing of vaccination. The effect of vaccination on all-cause death at one year was more pronounced in the group receiving early vaccination (HR 0.50; 95% CI, 0.29 to 0.86) compared late vaccination group (HR 0.75; 35% CI, 0.40 to 1.40) but there was no statistically significant difference between these groups (Interaction P = 0.335). In conclusion,there is insufficient evidence from the trial to establish whether there is a difference in efficacy between early and late vaccinationbut regardless of vaccination timing we strongly recommend influenza vaccination in all patients with cardiovascular diseases.

A Randomized Controlled Trial Comparing BioMime Sirolimus-Eluting Stent With Everolimus-Eluting Stent: Two-Year Outcomes of the meriT-V Trial.

Background: Drug-eluting stents (DESs) based on biodegradable polymers (BPs) have been introduced to reduce the risk for late and very late stent thrombosis (ST), which were frequently observed with earlier generations of DES designs based on durable polymers (DPs); however, randomized controlled trials on these DES designs are scarce. The meriT-V trial is a randomized, active-controlled, non-inferiority trial with a prospective, multicenter design that evaluated the 2-year efficacy of a novel third-generation, ultra-thin strut, BP-based BioMime sirolimus-eluting stent (SES) versus the DP-based XIENCE everolimus-eluting stent (EES) for the treatment of de novo lesions. Methods: The meriT-V is a randomized trial that enrolled 256 patients at 15 centers across Europe and Brazil. Here, we report the outcomes of the extended follow-up period of 2 years. The randomization of enrolled patients was in a 2:1 ratio; the enrolled patients received either the BioMime SES (n = 170) or the XIENCE EES (n = 86). The three-point major adverse cardiac event (MACE), defined as a composite of cardiac death, myocardial infarction (MI), or ischemia-driven target vessel revascularization (ID-TVR), was considered as the composite safety and efficacy endpoint. Ischemia-driven target lesion revascularization (ID-TLR) was evaluated as well as the frequency of definite/probable ST, based on the first Academic Research Consortium definitions. Results: The trial had a 2-year follow-up completion rate of 98.44% (n = 252/256 patients), and the clinical outcomes assessment showed a nonsignificant difference in the cumulative rate of three-point MACE between both arms (BioMime vs. XIENCE: 7.74% vs. 9.52%, P = 0.62). Even the MI incidences in the BioMime arm were insignificantly lower than those of the XIENCE arm (1.79% vs. 5.95%, P = 0.17). Late ST was observed in 1.19% cases of the XIENCE arm, while there were no such cases in the BioMime arm (P = 0.16). Conclusions: The objective comparisons between the novel BP-based BioMime SES and the well-established DP-based XIENCE EES in this randomized controlled trial show acceptable outcomes of both the devices in the cardiac deaths, MI, ID-TVR, and ST. Moreover, since there were no incidences of cardiac death in the entire study sample over the course of 2 years, we contend that the findings of the study are highly significant for both these DES designs. In this preliminary comparative trial, the device safety of BioMime SES can be affirmed to be acceptable, considering the lower three-point MACE rate and absence of late ST in the BioMime arm over the 2-year period.

A randomized controlled trial comparing BioMime Sirolimus-Eluting Stent with Everolimus-Eluting Stent: two-year outcomes of the meriT-V trial

BACKGROUND: Drug-eluting stents (DESs) based on biodegradable polymers (BPs) have been introduced to reduce the risk for late and very late stent thrombosis (ST), which were frequently observed with earlier generations of DES designs based on durable polymers (DPs); however, randomized controlled trials on these DES designs are scarce. The meriT-V trial is a randomized, active-controlled, non-inferiority trial with a prospective, multicenter design that evaluated the 2-year efficacy of a novel third-generation, ultra-thin strut, BP-based BioMime sirolimus-eluting stent (SES) versus the DP-based XIENCE everolimus-eluting stent (EES) for the treatment of de novo lesions. METHODS: The meriT-V is a randomized trial that enrolled 256 patients at 15 centers across Europe and Brazil. Here, we report the outcomes of the extended follow-up period of 2 years. The randomization of enrolled patients was in a 2:1 ratio; the enrolled patients received either the BioMime SES (n = 170) or the XIENCE EES (n = 86). The three-point major adverse cardiac event (MACE), defined as a composite of cardiac death, myocardial infarction (MI), or ischemia-driven target vessel revascularization (ID-TVR), was considered as the composite safety and efficacy endpoint. Ischemia-driven target lesion revascularization (ID-TLR) was evaluated as well as the frequency of definite/probable ST, based on the first Academic Research Consortium definitions. RESULTS: The trial had a 2-year follow-up completion rate of 98.44% (n = 252/256 patients), and the clinical outcomes assessment showed a nonsignificant difference in the cumulative rate of three-point MACE between both arms (BioMime vs. XIENCE: 7.74% vs. 9.52%, P = 0.62). Even the MI incidences in the BioMime arm were insignificantly lower than those of the XIENCE arm (1.79% vs.

Clinical impact of influenza vaccination after ST- and non-ST-segment elevation myocardial infarction - insights from the IAMI trial.

BACKGROUND: Influenza vaccination early after myocardial infarction (MI) improves prognosis but vaccine effectiveness may differ dependent on type of MI. METHODS: A total of 2,571 participants were prospectively enrolled in the Influenza vaccination after myocardial infarction (IAMI) trial and randomly assigned to receive in-hospital inactivated influenza vaccine or saline placebo. The trial was conducted at 30 centers in eight countries from October 1, 2016 to March 1, 2020. Here we report vaccine effectiveness in the 2,467 participants with ST-segment elevation MI (STEMI, n = 1,348) or non-ST-segment elevation MI (NSTEMI, n = 1,119). The primary endpoint was the composite of all-cause death, MI, or stent thrombosis at 12 months. Cumulative incidence of the primary and key secondary endpoints by randomized treatment and NSTEMI/STEMI was estimated using the Kaplan-Meier method. Treatment effects were evaluated with formal interaction testing to assess for effect modification. RESULTS: Baseline risk was higher in participants with NSTEMI. In the NSTEMI group the primary endpoint occurred in 6.5% of participants assigned to influenza vaccine and 10.5% assigned to placebo (hazard ratio [HR], 0.60; 95% CI, 0.39-0.91), compared to 4.1% assigned to influenza vaccine and 4.5% assigned to placebo in the STEMI group (HR, 0.90; 95% CI, 0.54-1.50, P = .237 for interaction). Similar findings were seen for the key secondary endpoints of all-cause death and cardiovascular death. The Kaplan-Meier risk difference in all-cause death at one year was more pronounced in participants with NSTEMI (NSTEMI: HR, 0.47; 95% CI 0.28-0.80, STEMI: HR, 0.86; 95% CI, 0.43-1.70, interaction P = .028). CONCLUSIONS: The beneficial effect of influenza vaccination on adverse cardiovascular events may be enhanced in patients with NSTEMI compared to those with STEMI.

Polymorphism rs7079 in miR-31/-584 Binding Site in Angiotensinogen Gene Associates with Earlier Onset of Coronary Artery Disease in Central European Population.

Angiotensinogen (AGT) represents a key component of the renin-angiotensin-aldosterone system (RAAS). Polymorphisms in the 3' untranslated region (3'UTR) of the AGT gene may alter miRNA binding and cause disbalance in the RAAS. Within this study, we evaluated the possible association of AGT +11525C/A (rs7079) with the clinical characteristics of patients with coronary artery diseases (CAD). Selective coronarography was performed in 652 consecutive CAD patients. Clinical characteristics of the patients, together with peripheral blood samples for DNA isolation, were collected. The genotyping of rs7079 polymorphism was performed with TaqMan® SNP Genotyping Assays. We observed that patients with the CC genotype were referred for coronarography at a younger age compared to those with the AA+CA genotypes (CC vs. AA+CA: 59.1 ± 9.64 vs. 60.91 ± 9.5 (years), p = 0.045). Moreover, according to the logistic regression model, patients with the CC genotype presented more often with restenosis than those with the CA genotype (p = 0.0081). In conclusion, CC homozygotes for rs7079 present with CAD symptoms at a younger age compared with those with the AA+CA genotype, and they are more prone to present with restenosis compared with heterozygotes.

The relationship between symptom onset-to-needle time and ischemic outcomes in patients with acute myocardial infarction treated with primary PCI: Observations from Prague-18 Study.

OBJECTIVES: Based on previous studies with clopidogrel, the time between acute myocardial infarction (AMI) symptoms onset and primary percutaneous coronary intervention (PCI) was proven as important prognostic factor. Our aim was to assess the relationship between symptoms onset to needle time (SNT) and procedural results and the occurrence of ischemic endpoints in primary angioplasty patients treated with potent P2Y12 inhibitors. METHODS: A total of 1,131 out of 1,230 patients randomized to the Prague-18 study (prasugrel vs. ticagrelor in primary PCI) were divided into a high and a low-risk group. The effect of defined SNT on patients' ischemic endpoints and prognosis by their risk status at admission was tested. RESULTS: The median SNT was 3.2 hours. Longer SNTs resulted in a more frequent incidence of TIMI flow <3 post PCI (p=0.015). There were significant differences in the occurrence of the combined ischemic endpoint among the compared SNT groups at 30 days (p=0.032), and 1 year (p=0.011), with the highest incidence in the ≤1 h SNT group of patients. "Latecomers" (SNT>4 hs) in the high-risk group experienced more reinfarction within 1 year [OR (95% CI) 3.23 (1.09-9.62) p=0.035]; no difference was found in the low-risk group. CONCLUSIONS: In the era of intense antithrombotic medication, stratification of MI patients undergoing primary angioplasty, based on initial ischemic risk assessment affected prognosis more than symptom onset to needle time. Longer time delay was significantly related to increased incidence of ischemic events and all-cause mortality only in patients with high ischemic risk.

Trends in outcomes of women with myocardial infarction undergoing primary angioplasty-Analysis of randomized trials.

Background: Sex- and gender-associated differences determine the disease response to treatment. Aim: The study aimed to explore the hypothesis that progress in the management of STE-myocardial infarction (STEMI) overcomes the worse outcome in women. Methods and results: We performed an analysis of three randomized trials enrolling patients treated with primary PCI more than 10 years apart. PRAGUE-1,-2 validated the preference of transport for primary PCI over on-site fibrinolysis. PRAGUE-18 enrollment was ongoing at the time of the functional network of 24/7PCI centers, and the intervention was supported by intensive antiplatelets. The proportion of patients with an initial Killip ≥ 3 was substantially higher in the more recent study (0.6 vs. 6.7%, p = 0.004). Median time from symptom onset to the door of the PCI center shortened from 3.8 to 3.0 h, p < 0.001. The proportion of women having total ischemic time ≤3 h was higher in the PRAGUE-18 (OR [95% C.I.] 2.65 [2.03-3.47]). However, the percentage of patients with time-to-reperfusion >6 h was still significant (22.3 vs. 27.2% in PRAGUE-18). There was an increase in probability for an initial TIMI flow >0 in the later study (1.49 [1.0-2.23]), and also for an optimal procedural result (4.24 [2.12-8.49], p < 0.001). The risk of 30-day mortality decreased by 61% (0.39 [0.17-0.91], p = 0.029). Conclusion: The prognosis of women with MI treated with primary PCI improved substantially with 24/7 regional availability of mechanical reperfusion, performance-enhancing technical progress, and intensive adjuvant antithrombotic therapy. A major modifiable hindrance to achieving this benefit in a broad population of women is the timely diagnosis by health professional services.

Stent Selection for Primary Angioplasty and Outcomes in the Era of Potent Antiplatelets. Data from the Multicenter Randomized Prague-18 Trial.

Drug-eluting stents (DES) are the recommended stents for primary percutaneous coronary intervention (PCI). This study aimed to determine why interventional cardiologists used non-DES and how it influenced patient prognoses. The efficacy and safety outcomes of the different stents were also compared in patients treated with either prasugrel or ticagrelor. Of the PRAGUE-18 study patients, 749 (67.4%) were treated with DES, 296 (26.6%) with bare-metal stents (BMS), and 66 (5.9%) with bioabsorbable vascular scaffold/stents (BVS) between 2013 and 2016. Cardiogenic shock at presentation, left main coronary artery disease, especially as the culprit lesion, and right coronary artery stenosis were the reasons for selecting a BMS. The incidence of the primary composite net-clinical endpoint (EP) (death, nonfatal myocardial infarction, stroke, serious bleeding, or revascularization) at seven days was 2.5% vs. 6.3% and 3.0% in the DES, vs. with BMS and BVS, respectively (HR 2.7; 95% CI 1.419-5.15, p = 0.002 for BMS vs. DES and 1.25 (0.29-5.39) p = 0.76 for BVS vs. DES). Patients with BMS were at higher risk of death at 30 days (HR 2.20; 95% CI 1.01-4.76; for BMS vs. DES, p = 0.045) and at one year (HR 2.1; 95% CI 1.19-3.69; p = 0.01); they also had a higher composite of cardiac death, reinfarction, and stroke (HR 1.66; 95% CI 1.0-2.74; p = 0.047) at one year. BMS were associated with a significantly higher rate of primary EP whether treated with prasugrel or ticagrelor. In conclusion, patients with the highest initial risk profile were preferably treated with BMS over BVS. BMS were associated with a significantly higher rate of cardiovascular events whether treated with prasugrel or ticagrelor.

Influenza Vaccination After Myocardial Infarction: A Randomized, Double-Blind, Placebo-Controlled, Multicenter Trial.

BACKGROUND: Observational and small, randomized studies suggest that influenza vaccine may reduce future cardiovascular events in patients with cardiovascular disease. METHODS: We conducted an investigator-initiated, randomized, double-blind trial to compare inactivated influenza vaccine with saline placebo administered shortly after myocardial infarction (MI; 99.7% of patients) or high-risk stable coronary heart disease (0.3%). The primary end point was the composite of all-cause death, MI, or stent thrombosis at 12 months. A hierarchical testing strategy was used for the key secondary end points: all-cause death, cardiovascular death, MI, and stent thrombosis. RESULTS: Because of the COVID-19 pandemic, the data safety and monitoring board recommended to halt the trial before attaining the prespecified sample size. Between October 1, 2016, and March 1, 2020, 2571 participants were randomized at 30 centers across 8 countries. Participants assigned to influenza vaccine totaled 1290 and individuals assigned to placebo equaled 1281; of these, 2532 received the study treatment (1272 influenza vaccine and 1260 placebo) and were included in the modified intention to treat analysis. Over the 12-month follow-up, the primary outcome occurred in 67 participants (5.3%) assigned influenza vaccine and 91 participants (7.2%) assigned placebo (hazard ratio, 0.72 [95% CI, 0.52-0.99]; P=0.040). Rates of all-cause death were 2.9% and 4.9% (hazard ratio, 0.59 [95% CI, 0.39-0.89]; P=0.010), rates of cardiovascular death were 2.7% and 4.5%, (hazard ratio, 0.59 [95% CI, 0.39-0.90]; P=0.014), and rates of MI were 2.0% and 2.4% (hazard ratio, 0.86 [95% CI, 0.50-1.46]; P=0.57) in the influenza vaccine and placebo groups, respectively. CONCLUSIONS: Influenza vaccination early after an MI or in high-risk coronary heart disease resulted in a lower risk of a composite of all-cause death, MI, or stent thrombosis, and a lower risk of all-cause death and cardiovascular death, as well, at 12 months compared with placebo. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02831608.

MiR-126-3p and MiR-223-3p as Biomarkers for Prediction of Thrombotic Risk in Patients with Acute Myocardial Infarction and Primary Angioplasty.

Aim. This study was designed to evaluate the relationship between microRNAs (miRNAs), miR-126-3p and miR-223-3p, as new biomarkers of platelet activation, and predicting recurrent thrombotic events after acute myocardial infarction (AMI). Methods and Results. The analysis included 598 patients randomized in the PRAGUE-18 study (ticagrelor vs. prasugrel in AMI). The measurements of miRNAs were performed by using a novel miRNA immunoassay method. The association of miRNAs with the occurrence of the ischemic endpoint (EP) (cardiovascular death, nonfatal MI, or stroke) and bleeding were analyzed. The miR-223-3p level was significantly related to an increased risk of occurrence of the ischemic EP within 30 days (odds ratio (OR) = 15.74, 95% confidence interval (CI): 2.07-119.93, p = 0.008) and one year (OR = 3.18, 95% CI: 1.40-7.19, p = 0.006), respectively. The miR-126-3p to miR-223-3p ratio was related to a decreased risk of occurrence of EP within 30 days (OR = 0.14, 95% CI: 0.03-0.61, p = 0.009) and one year (OR = 0.37, 95% CI: 0.17-0.82, p = 0.014), respectively. MiRNAs were identified as independent predictors of EP even after adjustment for confounding clinical predictors. Adding miR-223-3p and miR-126-3p to miR-223-3p ratios as predictors into the model calculating the ischemic risk significantly increased the predictive accuracy for combined ischemic EP within one year more than using only clinical ischemic risk parameters. No associations between miRNAs and bleeding complications were identified. Conclusion. The miR-223-3p and the miR-126-3p are promising independent predictors of thrombotic events and can be used for ischemic risk stratification after AMI.

The Prevalence of Dysglycemia-Based Chronic Disease in a European Population - a New Paradigm to Address Diabetes Burden: A Kardiovize Study.

OBJECTIVE: To determine the prevalence rate and associated risk factors for each stage of the Dysglycemia-Based Chronic Disease (DBCD) model, which 4 distinct stages and prompts early prevention to avert Diabetes and cardiometabolic complications. METHODS: Subjects between 25 and 64 years old from a random population-based sample were evaluated in Czechia from 2013 to 2014 using a cross-sectional design. DBCD stages were: stage 1 "insulin resistance" (inferred risk from abdominal obesity or a family history of diabetes); stage 2 "prediabetes"(fasting glucose between 5.6 and 6.9 mmol/L); stage 3 "type 2 diabetes (T2D)" (self-report of T2D or fasting glucose ≥7 mmol/L); and stage 4 "vascular complications" (T2D with cardiovascular disease). RESULTS: A total of 2147 subjects were included (57.8% women) with a median age of 48 years. The prevalence of each DBCD stage were as follows: 54.2% (stage 1); 10.3% (stage 2), 3.7% (stage 3); and 1.2% (stage 4). Stages 2 to 4 were more frequent in men and stage 1 in women (P < .001). Using binary logistic regression analysis adjusting by age/sex, all DBCD stages were strongly associated with abnormal adiposity, hypertension, dyslipidemia, and smoking status. Subjects with lower educational levels and lower income were more likely to present DBCD. CONCLUSION: Using the new DBCD framework and available metrics, 69.4% of the population had DBCD, identifying far more people at risk than a simple prevalence rate for T2D (9.2% in Czechia, 2013-2014). All stages were associated with traditional cardiometabolic risk factors, implicating common pathophysiologic mechanisms and a potential for early preventive care. The social determinants of health were related with all DBCD stages in alarming proportions and will need to be further studied.

Evidence for discrete modes of YAP1 signaling via mRNA splice isoforms in development and diseases.

Yes-associated protein 1 (YAP1) is a transcriptional co-activator downstream of Hippo pathway. The pathway exerts crucial roles in organogenesis and its dysregulation is associated with the spreading of different cancer types. YAP1 gene encodes for multiple protein isoforms, whose specific functions are not well defined. We demonstrate the splicing of isoform-specific mRNAs is controlled in a stage- and tissue-specific fashion. We designed expression vectors encoding for the most-represented isoforms of YAP1 with either one or two WW domains and studied their specific signaling activities in YAP1 knock-out cell lines. YAP1 isoforms display both common and unique functions and activate distinct transcriptional programs, as the result of their unique protein interactomes. By generating TEAD-based transcriptional reporter cell lines, we demonstrate individual YAP1 isoforms display unique effects on cell proliferation and differentiation. Finally, we illustrate the complexity of the regulation of Hippo-YAP1 effector in physiological and in pathological conditions of the heart.

Shockwave Lithotripsy vs Rotational Atherectomy: Mechanistic Differences From Optical Coherence Tomography.

Management of calcified coronary lesions remains challenging, with frequent stent underexpansion and suboptimal results, which lead to early and late stent failure. Appropriate lesion preparation and optimal stent expansion are the keys to prevent stent failure. We present an unusual case of extensive sever right coronary artery calcified stenosis, in which both rotational atherectomy (RA) and non-compliant balloons failed to dilate the lesion and finally the Shockwave lithotripsy balloon offered optimal lesion dilation and successful stent deployment. Furthermore, optical coherence tomography provided mechanistic insight into the differential effect of Shockwave balloon versus RA for extensively calcified lesions.