Amiloidosis cardiaca y cierre de aurícula izquierda. Estudio CAMYLAAC / Cardiac amyloidosis and left atrial appendage closure. The CAMYLAAC study

Introducción y objetivos: La amiloidosis cardiaca por transtirretina (ACTTR) se asocia con fibrilación auricular y un riesgo trombótico y hemorrágico aumentados. Nuestro objetivo fue evaluar los resultados del cierre percutáneo de orejuela izquierda (COI) comparado con pacientes sin diagnóstico conocido de ACTTR. Métodos: Comparación de la evolución a largo plazo de pacientes con diagnóstico de ACTTR frente a pacientes sin ese diagnóstico sometidos a COI entre 2009 y 2021. Resultados: Se incluyó a 1.159 pacientes de los que 40 (3,5%) fueron diagnosticados de ACTTR; fueron más ancianos, con más comorbilidades, mayores puntuaciones HAS-BLED y CHA2DS2-VASc y menor función ventricular izquierda. Se consiguió el COI exitoso en 1.137 pacientes (98,1%) sin diferencias entre los grupos. No hubo diferencias intrahospitalarias ni al seguimiento en ictus isquémico (5 frente a 2,5%, p=0,283), ictus hemorrágico (2,5 frente a 0,8%, p=0,284), ni sangrado mayor o menor. La mortalidad a 2 años no presentaba diferencias entre los pacientes con ACTTR y los que no presentaban este diagnóstico (20 frente a 13,6%, 0,248); sin embargo, a los 5 años los pacientes ACTTR presentaron mayor mortalidad (40 frente a 19,2%, p <0,001) pero no relacionada con complicaciones hemorrágicas o ictus isquémico. Conclusiones: El COI podría reducir complicaciones hemorrágicas y accidentes cerebrovasculares sin incrementar las complicaciones precoces en pacientes con ACTTR. Aunque la supervivencia a largo plazo en pacientes con ACTTR es muy reducida, a dos años fue comparable a la del grupo sin diagnóstico de ACTTR lo que sugiere que el COI no es fútil en pacientes con ACTTR. (AU)

Introduction and objectives: Transthyretin cardiac amyloidosis (ATTR-CA) patients often have atrial fibrillation and increased bleeding/thrombogenic risks. We aimed to evaluate outcomes of left atrial appendage closure (LAAC) compared with patients without a known diagnosis of CA. Methods: Comparison at long-term of patients diagnosed with ATTR-CA who underwent LAAC between 2009 and 2020 and those without a known diagnosis of CA. Results: We studied a total of 1159 patients. Forty patients (3.5%) were diagnosed with ATTR-CA; these patients were older and had more comorbidities, higher HAS-BLED and CHA2DS2-VASc scores, and lower left ventricular function. Successful LAAC was achieved in 1137 patients (98.1%) with no differences between groups. Regarding in-hospital and follow-up complications, there were no differences between the groups in ischemic stroke (5% vs 2.5% in those without a known diagnosis of CA; P=.283), hemorrhagic stroke (2.5% and 0.8% in the control group; P=.284), major or minor bleeding. At the 2-year follow-up, there were no significant differences in mortality (ATTR-CA: 20% vs those without known CA: 13.6%, 0.248); however, the at 5-year follow-up, ATTR-CA patients had higher mortality (40% vs 19.2%; P <.001) but this difference was unrelated to hemorrhagic complications or ischemic stroke. Conclusions: LAAC could reduce the risk of bleeding complications and ischemic cerebrovascular events without increasing the rate of early or mid-term complications. Although long-term survival was impaired in ATTR-CA patients, it was comparable to that of patients without a known diagnosis of CA at the 2-year follow-up, suggesting that LAAC for patients with ATTR-CA might not be futile. (AU)

Clinical Outcomes of Left Main Coronary Artery PCI With Rotational Atherectomy.

Data regarding rotational atherectomy percutaneous coronary intervention (RA PCI) angioplasty in the left main (LM) coronary artery are scarce, and mostly outdated. We aimed to describe clinical outcomes of RA PCI in LM. Patients requiring RA in 8 European countries and 19 centers were prospectively and consecutively included in the European registry of Cardiac Care of Calcified and Complex patients registry. In-hospital data collection and 1-year follow-up were performed for each patient. Between October 2016 and July 2018, 966 patients with complete data were included. Among them, 241 presented with an LM lesion, and 171 required an LM lesion preparation by RA. The latter, allocated to the LM-RA group, were compared with the 725 patients in the non-LM-RA group. Clinical success of the RA procedure was comparable in both groups, but in-hospital major adverse cardiac events were higher in the RA-LM group (7.6% vs 3.2%, adjusted p = 0.04), mainly driven by a higher in-hospital mortality rate (5.3 vs 0.3%, adjusted p = 0.005). At 1-year follow-up, mortality and major adverse cardiac event rates were comparable in both groups (12.9% vs 8.0%, adjusted p value: 0.821, and 15.8% vs 10.9%, adjusted p value: 0.329, respectively), but the rate of target vessel revascularization remained higher in the RA-LM group (5.3% vs 3.2%, adjusted p = 0.021). In conclusion, RA PCI is an efficient option for calcified LM lesions, providing acceptable outcomes regarding this population with high risk at 1 year, and yields comparable outcomes with RA PCI performed on non-LM lesions.

Cardiac amyloidosis and left atrial appendage closure. The CAMYLAAC study.

INTRODUCTION AND OBJECTIVES: Transthyretin cardiac amyloidosis (ATTR-CA) patients often have atrial fibrillation and increased bleeding/thrombogenic risks. We aimed to evaluate outcomes of left atrial appendage closure (LAAC) compared with patients without a known diagnosis of CA. METHODS: Comparison at long-term of patients diagnosed with ATTR-CA who underwent LAAC between 2009 and 2020 and those without a known diagnosis of CA. RESULTS: We studied a total of 1159 patients. Forty patients (3.5%) were diagnosed with ATTR-CA; these patients were older and had more comorbidities, higher HAS-BLED and CHA2DS2-VASc scores, and lower left ventricular function. Successful LAAC was achieved in 1137 patients (98.1%) with no differences between groups. Regarding in-hospital and follow-up complications, there were no differences between the groups in ischemic stroke (5% vs 2.5% in those without a known diagnosis of CA; P=.283), hemorrhagic stroke (2.5% and 0.8% in the control group; P=.284), major or minor bleeding. At the 2-year follow-up, there were no significant differences in mortality (ATTR-CA: 20% vs those without known CA: 13.6%, 0.248); however, the at 5-year follow-up, ATTR-CA patients had higher mortality (40% vs 19.2%; P <.001) but this difference was unrelated to hemorrhagic complications or ischemic stroke. CONCLUSIONS: LAAC could reduce the risk of bleeding complications and ischemic cerebrovascular events without increasing the rate of early or mid-term complications. Although long-term survival was impaired in ATTR-CA patients, it was comparable to that of patients without a known diagnosis of CA at the 2-year follow-up, suggesting that LAAC for patients with ATTR-CA might not be futile.

Impact of operators experience on peri-procedural outcomes with Watchman FLX: Insights from the FLX-SPA registry.

BACKGROUND: The Watchman FLX is a device upgrade of the Watchman 2.5 that incorporates several design enhancements intended to simplify left atrial appendage occlusion (LAAO) and improve procedural outcomes. This study compares peri-procedural results of LAAO with Watchman FLX (Boston Scientific, Marlborough, Massachusetts) in centers with varying degrees of experience with the Watchman 2.5 and Watchman FLX. METHODS: Prospective, multicenter, "real-world" registry including consecutive patients undergoing LAAO with the Watchman FLX at 26 Spanish sites (FLX-SPA registry). Implanting centers were classified according to the center's prior experience with the Watchman 2.5. A further division of centers according to whether or not they had performed ≤ 10 or > 10Watchman FLX implants was prespecified at the beginning of the study. Procedural outcomes of institutions stratified according to their experience with the Watchman 2.5 and FLX devices were compared. RESULTS: 359 patients [mean age 75.5 (SD8.1), CHA2DS2-VASc 4.4 (SD1.4), HAS-BLED 3.8(SD0.9)] were included. Global success rate was 98.6%, successful LAAO with the first selected device size was achieved in 95.5% patients and the device was implanted at first attempt in 78.6% cases. There were only 9(2.5%) major peri-procedural complications. No differences in efficacy or safety results according to the centers previous experience with Watchman 2.5 and procedural volume with Watchman FLX existed. CONCLUSIONS: The Watchman FLX attains high procedural success rates with complete LAA sealing in unselected, real-world patients, along with a low incidence of peri-procedural complications, regardless of operators experience with its previous device iteration or the number of Watchman FLX devices implanted.

Effect of Sex on Outcomes of Coronary Rotational Atherectomy Percutaneous Coronary Intervention (From the European Multicenter Euro4C Registry).

Data regarding the potential influence of gender on outcomes of rotational atherectomy (RA) percutaneous coronary intervention (PCI) are scarce and conflicting. Using the Euro4C registry, an international prospective multicentric registry of RA PCI, we evaluated the influence of gender on clinical outcomes of RA PCI. Between October 2016 and July 2018, 966 patients were included. In them, 267 (27.6%) were females. Female patients were older than males (77.7 years old ± 9.8 vs 73.3 ± 9.5 years old respectively, p < 0.001) had a poorer renal function (43,1% of females had a GFR < 60 ml/min:1.73m² vs 30.4% of males, p < 0.001) and were more frequently admitted for an acute coronary syndrome (32.2% vs 22.3% p = 0.002). During RA procedure, women were less likely to be treated by radial approach (65.0% vs 74.4%, p = 0.004). In-hospital major adverse cardiac event rate-defined as cardiovascular death, myocardial infarction, stroke/transient ischemic attack, target lesion revascularization, and coronary artery bypass grafting surgery-was higher in the female group (7.1% vs 3.7%, p = 0.043). However, coronary perforation, dissection, slow/low flow and tamponade did not significantly differ in gender, neither did cardiovascular medications at discharge. At 1 year follow-up, rate of major adverse cardiac event was 18.4% in the female group vs 11.2% in the male group (adjusted Hazard Ratio 1.82 [1.24 to 2.67], p = 0.002). No significant bleeding differences were observed in gender, neither in hospital, nor during follow-up. In conclusion women had worse clinical outcomes following RA PCI during hospitalization and at 1 year follow-up than did men.

Impact of Anemia on the Risk of Bleeding Following Percutaneous Coronary Interventions in Patients ≥75 Years of Age.

Bleeding risk stratification is an unresolved issue in older adults. Anemia may reflect subclinical blood losses that can be exacerbated after percutaneous coronary intervention . We sought to prospectively determine the contribution of anemia to the risk of bleeding in 448 consecutive patients aged 75 or more years, treated by percutaneous coronary interventions without concomitant indication for oral anticoagulation. We evaluated the effect of WHO-defined anemia on the incidence of 1-year nonaccess site-related major bleeding. The prevalence of anemia was 39%, and 13.1% of anemic and 5.2% of nonanemic patients suffered a bleeding event (hazard ratio 2.75, 95% confidence interval 1.37 to 5.54, p = 0.004). Neither PRECISE-DAPT nor CRUSADE scores were superior to hemoglobin for the prediction of bleeding. In conclusion, anemia is a powerful predictor of bleeding with potential utility for simplifying tailoring therapies.

Nutritional preconditioning by marine omega-3 fatty acids in patients with ST-segment elevation myocardial infarction: A METOCARD-CNIC trial substudy.

BACKGROUND: Marine omega-3 eicosapentaenoic acid (EPA) is readily incorporated into cardiomyocyte membranes, partially displacing the omega-6 arachidonic acid (AA). Whereas AA is a substrate for pro-inflammatory eicosanoids, the release of EPA from cell membranes generates anti-inflammatory lipid mediators, contributing to the infarct-limiting effect observed experimental models. Clinical data are lacking. METHODS: In this observational study conducted in 100 patients with a reperfused anterior ST-elevation myocardial infarction (STEMI), at hospital admission we quantified by gas-chromatography the red blood cell proportions of AA, EPA, and the AA:EPA ratio, a valid surrogate for cardiomyocyte membrane content. Patients underwent cardiac magnetic resonance imaging in the acute phase (one week post-STEMI), and at long-term (6 months) follow-up. Infarct size (delayed gadolinium enhancement) and cardiac function (left ventricular ejection fraction [LVEF]) were correlated with exposures of interest by multivariate regression analysis. RESULTS: AA:EPA ratio directly related to acute infarct size (coefficient [95% CI]: 6.19 [1.68 to 10.69], P = 0.008) and inversely to long-term LVEF (coefficient [95% CI]: − 4.02 [− 7.15 to − 0.89], P = 0.012). EPA inversely related to acute infarct size (coefficient [95% CI]: − 6.58; [− 11.46 to − 1.70]; P = 0.009), while a direct association with LVEF at follow-up (coefficient [95% CI]: 3.67 [0.25 to 7.08]; P = 0.036) was observed. CONCLUSIONS: A low AA:EPA ratio in red blood cells at the time of STEMI is associated with smaller acute infarct size and preserved long-term ventricular function. Our results are consistent with prior work in experimental models and add to the notion of omega-3 fatty acids as a healthy fat. TRIAL REGISTRATION: http://www.clinicaltrials.gov/NCT01311700

Neoatherosclerosis causing occlusive in-stent restenosis: Impact of intracoronary imaging in the intensity of lipid-lowering therapy.

The unique physical properties of optical coherence tomography (OCT) make it a useful technique in the study of restenosis mechanisms. In fact, OCT is able to differentiate between neointimal proliferation and neoatherosclerosis within the stent. We report a rare case of occlusive neoatherosclerosis presenting beyond one year after a successful drug-eluting stent implantation. The impact of OCT findings in the clinical decision making process is emphasized.

European expert consensus on rotational atherectomy.

The interest in rotational atherectomy (RA) has increased over the past decade as a consequence of more complex and calcified coronary stenoses being attempted with percutaneous coronary interventions. Yet adoption of RA is hampered by several factors: amongst others, by the lack of a standardised protocol. This European expert consensus document stems from the awareness of the large heterogeneity in the protocols adopted to perform rotational atherectomy. The objective of the present document is to provide some points of consensus among highly experienced operators on the most controversial steps of RA in an attempt to build the basis of a standardised and universally accepted protocol.

Functional impact of high clopidogrel maintenance dosing in patients undergoing elective percutaneous coronary interventions. Results of a randomized study.

The currently recommended maintenance dose of clopidogrel is often associated with inadequate platelet inhibition, suggesting the need for a higher dose. The aim of this pilot study was to assess the functional impact of a high (150 mg/day) maintenance dose of clopidogrel in patients undergoing elective percutaneous coronary intervention (PCI). This is a prospective, randomized, platelet function study which was performed in elective PCI patients assigned to treatment with either a 75 mg (n = 20) or 150 mg (n = 20) daily maintenance dose of clopidogrel for 30 days; afterwards, all patients resumed standard dosing. Platelet aggregation was performed using light transmittance aggregometry following 20 microM and 5 microM adenosine diphosphate (ADP) stimuli 30 days after randomization and 30 days after resuming standard dosing. Patients treated with 150 mg/day clopidogrel had lower 20 microM ADP-induced platelet aggregation compared to patients on 75 mg/day (52.1 +/- 9% vs. 64.0 +/- 8%; p < 0.001; primary endpoint). The dose-dependent effect was confirmed by the absolute and relative increase in platelet aggregation after resuming standard dosing (p < 0.001). No changes were observed in patients randomized to standard dosing. Parallel findings were observed following 5 microM ADP stimuli for all assessments. A broad variability in clopidogrel-induced antiplatelet effects was observed irrespective of dosing. In conclusion, a 150 mg/day maintenance dose regimen of clopidogrel is associated with reduced platelet reactivity and enhanced platelet inhibition compared to that achieved with the currently recommended 75 mg/day in patients undergoing elective PCI.

Impact of platelet reactivity on cardiovascular outcomes in patients with type 2 diabetes mellitus and coronary artery disease.

OBJECTIVES: This study sought to determine the prognostic implications of high platelet reactivity (HPR) assessed in type 2 diabetes mellitus (T2DM) patients while in their steady-state phase of dual antiplatelet therapy. BACKGROUND: Type 2 diabetes mellitus patients have increased platelet reactivity compared with nondiabetic patients. Whether HPR assessed in T2DM while in their steady-state phase of dual antiplatelet therapy is associated with an increased risk of major adverse cardiovascular events (MACE) is unknown. METHODS: Platelet function analyses, which included measures of platelet aggregation and activation, were performed in 173 T2DM patients with coronary artery disease on chronic treatment with aspirin and clopidogrel. The HPR was defined as the upper quartile of maximal platelet aggregation (Agg(max)) after 20 micromol/l adenosine diphosphate stimuli. Patients were followed up for 2 years and MACE were recorded. RESULTS: A total of 41 MACE occurred in 34 patients (19.7%) during the 2-year follow-up. The MACE occurred in 15.2%, 12.2%, 12.2%, and 37.7% of patients from the lowest to upper quartile, respectively (p = 0.005). The HPR was the strongest independent predictor of MACE (hazard ratio 3.35, 95% confidence interval [CI] 1.68 to 6.66, p = 0.001). Receiver-operating characteristic analysis indicated that a cutoff value of 62% Agg(max) best predicted MACE (37.8% vs. 13.2%, odds ratio 3.96, 95% CI 1.8 to 8.7, p < 0.001). Patients with HPR had up-regulation of multiple platelet signaling pathways (p < 0.0001 for all assays), indicative of a global hyperreactive platelet status. CONCLUSIONS: High platelet reactivity determined in T2DM patients with coronary artery disease while on chronic dual antiplatelet therapy is associated with a higher risk of long-term adverse cardiovascular events, suggesting the need for tailored antithrombotic drug regimens in these high-risk patients.

Myocardial perfusion imaging with adenosine triphosphate predicts the rate of cardiovascular events.

BACKGROUND: Adenosine triphosphate (ATP) has effects similar to adenosine, including a very short half-life, with the advantage of a much lower cost. Our aim was to evaluate whether myocardial single photon emission computed tomography (SPECT) with ATP can predict the rate of hard events. METHODS AND RESULTS: We studied 299 patients (188 men; mean age, 64 +/- 10 years) with known or suspected coronary disease with thallium 201 SPECT during ATP infusion and at rest. Perfusion defects were divided into the following: absent/mild reversible, moderate/severe reversible, and mixed/fixed. During a maximum follow-up of 87 months (mean, 32.7 +/- 20.3 months), the rate of cardiovascular events was studied. The prognostic value of different variables that can influence survival was calculated with the Cox proportional hazards model. The total number of cardiovascular events was 115 (43 hard events). The annual rate of hard events according to type of perfusion defect was 3.44% (95% confidence interval [CI], 2.12-5.26) for absent/mild reversible, 6.06% (95% CI, 2.23-13.20) for moderate/severe reversible, and 15.12% (95% CI, 8.64-24.55) for mixed/fixed. In the Cox model the variables that significantly predicted hard events were age greater than 55 years (P = .0293), diabetes (P = .0036), and severe perfusion defects (P = .0008). CONCLUSION: ATP can be used for pharmacologic stress testing. SPECT with ATP has a stronger correlation with the rate of hard events than clinical variables.