STREAM-2: Half-Dose Tenecteplase or Primary Percutaneous Coronary Intervention in Older Patients With ST-Segment-Elevation Myocardial Infarction: A Randomized, Open-Label Trial.

BACKGROUND: ST-segment-elevation myocardial infarction (STEMI) guidelines recommend pharmaco-invasive treatment if timely primary percutaneous coronary intervention (PCI) is unavailable. Full-dose tenecteplase is associated with an increased risk of intracranial hemorrhage in older patients. Whether pharmaco-invasive treatment with half-dose tenecteplase is effective and safe in older patients with STEMI is unknown. METHODS: STREAM-2 (Strategic Reperfusion in Elderly Patients Early After Myocardial Infarction) was an investigator-initiated, open-label, randomized, multicenter study. Patients ≥60 years of age with ≥2 mm ST-segment elevation in 2 contiguous leads, unable to undergo primary PCI within 1 hour, were randomly assigned (2:1) to half-dose tenecteplase followed by coronary angiography and PCI (if indicated) 6 to 24 hours after randomization, or to primary PCI. Efficacy end points of primary interest were ST resolution and the 30-day composite of death, shock, heart failure, or reinfarction. Safety assessments included stroke and nonintracranial bleeding. RESULTS: Patients were assigned to pharmaco-invasive treatment (n=401) or primary PCI (n=203). Median times from randomization to tenecteplase or sheath insertion were 10 and 81 minutes, respectively. After last angiography, 85.2% of patients undergoing pharmaco-invasive treatment and 78.4% of patients undergoing primary PCI had ≥50% resolution of ST-segment elevation; their residual median sums of ST deviations were 4.5 versus 5.5 mm, respectively. Thrombolysis In Myocardial Infarction flow grade 3 at last angiography was ≈87% in both groups. The composite clinical end point occurred in 12.8% (51/400) of patients undergoing pharmaco-invasive treatment and 13.3% (27/203) of patients undergoing primary PCI (relative risk, 0.96 [95% CI, 0.62-1.48]). Six intracranial hemorrhages occurred in the pharmaco-invasive arm (1.5%): 3 were protocol violations (excess anticoagulation in 2 and uncontrolled hypertension in 1). No intracranial bleeding occurred in the primary PCI arm. The incidence of major nonintracranial bleeding was low in both groups (<1.5%). CONCLUSIONS: Halving the dose of tenecteplase in a pharmaco-invasive strategy in this early-presenting, older STEMI population was associated with electrocardiographic changes that were at least comparable to those after primary PCI. Similar clinical efficacy and angiographic end points occurred in both treatment groups. The risk of intracranial hemorrhage was higher with half-dose tenecteplase than with primary PCI. If timely PCI is unavailable, this pharmaco-invasive strategy is a reasonable alternative, provided that contraindications to fibrinolysis are observed and excess anticoagulation is avoided. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT02777580.

Electroencephalographic guided propofol-remifentanil TCI anesthesia with and without dexmedetomidine in a geriatric population: electroencephalographic signatures and clinical evaluation.

Elderly and multimorbid patients are at high risk for developing unfavorable postoperative neurocognitive outcomes; however, well-adjusted and EEG-guided anesthesia may help titrate anesthesia and improve postoperative outcomes. Over the last decade, dexmedetomidine has been increasingly used as an adjunct in the perioperative setting. Its synergistic effect with propofol decreases the dose of propofol needed to induce and maintain general anesthesia. In this pilot study, we evaluate two highly standardized anesthetic regimens for their potential to prevent burst suppression and postoperative neurocognitive dysfunction in a high-risk population. Prospective, randomized clinical trial with non-blinded intervention. Operating room and post anesthesia care unit at Hospital Base San José, Osorno/Universidad Austral, Valdivia, Chile. 23 patients with scheduled non-neurologic, non-cardiac surgeries with age > 69 years and a planned intervention time > 60 min. Patients were randomly assigned to receive either a propofol-remifentanil based anesthesia or an anesthetic regimen with dexmedetomidine-propofol-remifentanil. All patients underwent a slow titrated induction, followed by a target controlled infusion (TCI) of propofol and remifentanil (n = 10) or propofol, remifentanil and continuous dexmedetomidine infusion (n = 13). We compared the perioperative EEG signatures, drug-induced changes, and neurocognitive outcomes between two anesthetic regimens in geriatric patients. We conducted a pre- and postoperative Montreal Cognitive Assessment (MoCa) test and measured the level of alertness postoperatively using a sedation agitation scale to assess neurocognitive status. During slow induction, maintenance, and emergence, burst suppression was not observed in either group; however, EEG signatures differed significantly between the two groups. In general, EEG activity in the propofol group was dominated by faster rhythms than in the dexmedetomidine group. Time to responsiveness was not significantly different between the two groups (p = 0.352). Finally, no significant differences were found in postoperative cognitive outcomes evaluated by the MoCa test nor sedation agitation scale up to one hour after extubation. This pilot study demonstrates that the two proposed anesthetic regimens can be safely used to slowly induce anesthesia and avoid EEG burst suppression patterns. Despite the patients being elderly and at high risk, we did not observe postoperative neurocognitive deficits. The reduced alpha power in the dexmedetomidine-treated group was not associated with adverse neurocognitive outcomes.

Performance of the SEDLine Monitor: Age Dependency and Time Delay.

BACKGROUND: Devices monitoring the hypnotic component of general anesthesia can help to guide anesthetic management. The main purposes of these devices are the titration of anesthesia dose. While anesthesia at low doses can result in awareness with intraoperative memory formation, excessive administration of anesthetics may be associated with an increased risk of postoperative neurocognitive disorder. We have previously shown for various indices that they are significantly influenced by the patient's age and that the monitors have a significant time delay. Here, we evaluated the influence of patient's age and time delay on the patient state index (PSI) of the SEDLine monitor. METHODS: To analyze the influence of the patient's age, we replayed 2 minutes of electroencephalography (EEG) of 141 patients (19-88 years, ASA I-IV) undergoing general anesthesia maintained with desflurane, sevoflurane, or propofol to the SEDLine monitor. We extracted the PSI as well as the spectral edge frequency (SEF) and performed a linear regression analysis. For evaluation of the time delay, we replayed 5 minutes of EEG of stable episodes of adequate anesthesia (PSI between 25 and 50) or light sedation/wake (PSI >70) in different orders to the SEDLine to simulate sudden changes between the states. Time delays were defined as the required time span of the monitor to reach the stable target index. RESULTS: PSI and SEF increased significantly with the patient's age. These findings did not depend on the administered anesthetic. The evaluation of the correlation between SEF and PSI showed a strong correlation with Spearman's correlation coefficient of ρ = 0.86 (0.82; 0.89). The time delays depended on the type of transition. We found a median time delay of 54 (Min: 46; Max: 61) seconds for the important transition between adequate anesthesia and awake and 55 (Min: 50; Max: 67) seconds in the other direction. CONCLUSIONS: With our analyses, we show that the indices presented on the SEDLine display, the PSI and the SEF, increase with age for patients under general anesthesia. Additionally, a delay of the PSI to react to sudden neurophysiologic changes due to dose of the maintenance anesthetic is of a time course that is clinically significant. These factors should be considered when navigating anesthesia relying on only the proprietary index for the SEDLine monitor.

Outcomes of a modified, low-cost, veno-arterial extracorporeal membrane oxygenation (V-A ECMO) for elective, periprocedural support of high-risk percutaneous cardiac interventions: An experience from a latinamerican center.

INTRODUCTION: High-risk procedures in interventional cardiology include a wide spectrum of clinical and anatomical scenarios related to a higher periprocedural morbidity and mortality. The prophylactic use of short-term mechanical circulatory support (ST-MCS) may improve both the safety and efficacy of the intervention by leading to more stable procedural hemodynamics. However, the significant costs may limit its use in resource constrained settings. To overcome this limitation, we ideated a modified, low-cost, veno-arterial extracorporeal membrane oxygenator (V-A ECMO) setup. METHODS: We conducted an observational prospective study including all patients undergoing a high-risk interventional cardiology procedure at our institution under prophylactic ST-MCS using a modified, low-cost version of V-A ECMO, where some components of the standard V-A ECMO circuit were replaced by supplies used for cardiac surgical cardiopulmonary bypass, achieving a cost reduction of 72%. We assessed in-hospital and mid-term outcomes, including procedural success, post-procedure complications and mortality. RESULTS: Between March 2016 and December 2021, ten patients underwent high-risk IC procedures with prophylactic use of V-A ECMO. Isolated percutaneous intervention (PCI) was performed in six patients, isolated transcatheter aortic valve replacement (TAVR) in two, and a combined procedure (PCI + TAVR) in two. Mean ejection fraction was 34% (range 20-64%). Mean STS PROM was 16.2% (range 9.5-35.8%) and mean EuroScore was 23.7% (range 1.5-60%). The planned intervention was successfully performed in all cases. There were no reports of V-A ECMO malfunction. In nine patients the VA-ECMO was withdrawn immediately after the procedure but one patient required extended - 24 h - support with no significant issues. One patient experienced a periprocedural myocardial infarction and another developed a femoral pseudoaneurysm. In-hospital and 30-day survival were 100%, and 1-year survival was 80%. CONCLUSIONS: High-risk procedures in interventional cardiology can be successfully performed under prophylactic ST-MCS using a modified, low-cost V-A ECMO, suitable for limited-resource settings.

Linear thinking does not reflect the newer 21st-century anesthesia concepts. A narrative review.

The brain constitutes a good example of a chaotic, nonlinear biological system where large neuronal networks operate chaotically with random connectivity. This critical state is significantly affected by the anesthetic loss of consciousness induced by drugs whose pharmacological behavior has been classically based on linear kinetics and dynamics. Recent developments in pharmacology and brain monitoring during anesthesia suggest a different view that we tried to explore in this article. The concepts of effect-site for hypnotic drugs modeling a maximum effect, electroencephalographic dynamics during induction, maintenance, and recovery from anesthesia are discussed, integrated into this alternative view, and how it may be applied in daily clinical practice.

[Transcatheter aortic-valve implantation. A ten years clinical experience]. / Resultados del implante percutáneo de válvula aórtica (TAVI). Experiencia después de la primera década desde la introducción de la técnica.

BACKGROUND: Transcatheter aortic-valve implantation (TAVI) was introduced in 2002 and the first implants in our country were performed in 2010. AIM: To review the TAVI experience in our hospital, considering the technology improvements and gained experience throughout this period. MATERIAL AND METHODS: All patients undergoing TAVI in our center were included. Results and complications were adjudicated according to the Valve Academic Research Consortium-2 (VARC-2) criteria. Patients were divided in 3 groups, according to procedural year: Period 1: 2010-2015 (n = 35); Period 2: 2016-2018 (n = 35); Period 3: 2019-2021 (n = 41). Mortality up to one year after the procedure was recorded. RESULTS: Between 2010 and 2021, 111 TAVI procedures were performed. The mean age of patients was 82 years and 47% were women. Risk scores for in-hospital mortality were STS 6.7%, EUROSCORE II 8.0% and ACC/STS TAVR Score 4.9%. The trans-femoral route was used in 88% and a balloon-expandable valve was chosen in 82% of patients. A successful implant was achieved in 96%, with an in-hospital mortality of 1.8%. Mortality at 30 days and 1-year were 2.7 and 9.0%, respectively. During period 3, 100% of implants were successful, with no in-hospital mortality, less vascular complications (p < 0.01), less stroke (p = 0.04), less severe paravalvular leak (p = 0.01) and significantly lower rate of acute complications (p < 0.01). CONCLUSIONS: TAVI achieves excellent results. With greater experience and better available technologies, these results are even more favorable.

Mid-term follow-up of balloon pulmonary angioplasty for inoperable chronic thromboembolic pulmonary hypertension: An experience in Latin America.

OBJECTIVES: To describe the characteristics of patients who undergo balloon pulmonary angioplasty (BPA) for inoperable chronic thromboembolic pulmonary hypertension (CTEPH) and report the mid-term outcomes. BACKGROUND: BPA has been recently introduced in Latin America. Mid-term results have not been published. METHODS: Prospective Chilean Registry of inoperable CTEPH patients who underwent BPA. Clinical variables were analyzed at baseline, after each procedure and at follow-up. Hemodynamic variables were recorded before and after the last BPA. RESULTS: Between August 2016 and September 2019, 22 patients (17 women), 59 ± 12.7 years, underwent 81 BPA and were followed for as long as 33.1 months (mean 17.3 ± 7.5). Mean pulmonary artery pressure decreased by 17.4% (51.1 ± 12 vs. 42.2 ± 13 mmHg, p = .001), pulmonary vascular resistance by 23.9% (766.7 ± 351 vs. 583 ± 346 dynes/s/cm-5 , p = .001), cardiac index increased by 8% (2.3 ± 0.54 vs. 2.5 ± 0.54 L/min/m2 , p = .012), N-terminal pro-B-type natriuretic peptide decreased by 73.8% (1,685 ± 1,045 vs. 441.8 ± 276 pg/dl, p = .006), and 6-min walk distance improved by 135 m (316.7 ± 94 vs. 451.1 ± 113 m, p = .001). One patient (4.5%) developed lung reperfusion injury and four patients (18.2%) had minor bleeding (hemoptysis), after the procedure. There was no mortality associated with BPA. CONCLUSIONS: Our results confirm that BPA for inoperable CTEPH is a relatively safe procedure that improves clinical and hemodynamic parameters in the mid-term. This therapy should be considered as an alternative, mainly in places where access to PAH therapy or surgery is restricted.

Combination Therapy with Oral Treprostinil for Pulmonary Arterial Hypertension. A Double-Blind Placebo-controlled Clinical Trial.

Rationale: Oral treprostinil improves exercise capacity in patients with pulmonary arterial hypertension (PAH), but the effect on clinical outcomes was unknown.Objectives: To evaluate the effect of oral treprostinil compared with placebo on time to first adjudicated clinical worsening event in participants with PAH who recently began approved oral monotherapy.Methods: In this event-driven, double-blind study, we randomly allocated 690 participants (1:1 ratio) with PAH to receive placebo or oral treprostinil extended-release tablets three times daily. Eligible participants were using approved oral monotherapy for over 30 days before randomization and had a 6-minute-walk distance 150 m or greater. The primary endpoint was the time to first adjudicated clinical worsening event: death; hospitalization due to worsening PAH; initiation of inhaled or parenteral prostacyclin therapy; disease progression; or unsatisfactory long-term clinical response.Measurements and Main Results: Clinical worsening occurred in 26% of the oral treprostinil group compared with 36% of placebo participants (hazard ratio, 0.74; 95% confidence interval, 0.56-0.97; P = 0.028). Key measures of disease status, including functional class, Borg dyspnea score, and N-terminal pro-brain natriuretic peptide, all favored oral treprostinil treatment at Week 24 and beyond. A noninvasive risk stratification analysis demonstrated that oral treprostinil-assigned participants had a substantially higher mortality risk at baseline but achieved a lower risk profile from Study Weeks 12-60. The most common adverse events in the oral treprostinil group were headache, diarrhea, flushing, nausea, and vomiting.Conclusions: In participants with PAH, addition of oral treprostinil to approved oral monotherapy reduced the risk of clinical worsening.Clinical trial registered with www.clinicaltrials.gov (NCT01560624).

Influence of age on functional capacity and work ability in Chilean workers: a cross-sectional study.

OBJECTIVE: To determine if there are differences in functional capacity and work ability between older and younger active workers in public institutions, and to relate functional capacity to work ability. METHODS: This cross-sectional study evaluated 360 subjects from two public institutions, a university and a high-complexity regional hospital. The participants were divided into 3 age ranges 40-49, 50-59 and ≥ 60 years. The following evaluations were applied: a multidimensional assessment questionnaire, work ability and functional capacity using physical tests (strength, flexibility and balance). RESULTS: There are no significant differences in work ability among the different age groups (P > 0.05). Significant differences were found according to age group in 30-s chair-stand test (30-s CST), 1 repetition maximum (1RM) extending the knee 90° (1RM-leg extension) and 1RM of handgrip strength (1RM-handgrip), upper body flexibility, lower body flexibility, static balance or dynamic balance (P < 0.05). Only the variables 30-s CST (rs = 0.13, P = 0.018), lower body flexibility (rs = 0.13, P = 0.012) and static balance (rs = 0.13, P = 0.012) were related to work ability. CONCLUSIONS: There are differences in functional capacity as the workers' ages increase. By contrast, work ability does not present any differences when comparing older and younger adults. Some physical tests of the lower extremities presented a small correlation with work ability.

[Balloon pulmonary angioplasty for the treatment of chronic thromboembolic pulmonary hypertension]. / Angioplastía con balón para el tratamiento de la hipertensión arterial pulmonar por enfermedad tromboembólica crónica. Resultados hemodinámicos y clínicos inmediatos.

BACKGROUND: Balloon pulmonary angioplasty (BPA) is a therapeutic alternative for patients with inoperable chronic thromboembolic pulmonary hypertension (CTEPH). AIM: To report the initial experience with the "refined BPA technique" with the use of intravascular images. PATIENTS AND METHODS: Between June 2015 and June 2016 we selected fourteen patients with CTEPH who were considered candidates for BPA. Lesions targeted for treatment were further analyzed using intravascular imaging with optical frequency domain imaging (OFDI). We report the immediate hemodynamic results and four weeks of follow-up of the first eight patients of this series. RESULTS: We performed 16 BPA in eight patients aged 61 ± 14 years (88% women). Mean pulmonary artery pressure (PAPm) was 48.6 ± 5.8 mmHg. Success was achieved in seven patients (88%). A mean of 2.3 segments per patient were intervened in 11 sessions (1.6 sessions/ patient). Only one patient developed lung reperfusion injury. No mortality was associated with the procedure. After the last BPA session, PAPm decreased to 37.4 ± 8.6 mmHg (p=0.02). Pulmonary vascular resistance (RVP) decreased from 858,6 ± 377,0 at baseline to 516,6 ± 323,3 Dynes/sec/cm-5 (p<0.01) and the cardiac index increased from 2.4±0.6 at baseline to 2.8±0.3 L/min/m2 (p=0.01). At 4 weeks after the last BPA, WHO functional class improved from 3.3±0.5 to 2.5±0.5 (p<0,01) and six minutes walking distance from 331±92 to 451±149 m (p=0.01). CONCLUSIONS: BPA guided by OFDI for the treatment of inoperable CTEPH patients is a safe alternative with excellent immediate hemodynamic and clinical results.

Effect-Site Target-Controlled Infusion in the Obese: Model Derivation and Performance Assessment.

BACKGROUND: The aim of this study is to derive a propofol pharmacokinetic (PK) pharmacodynamic (PD) model to perform effect-site target-controlled infusion (TCI) in obese patients, and to analyze its performance along with that of other available PK models. METHODS: In the first step of the study, a 3-compartment PK model linked to a sigmoidal inhibitory Emax PD model by a first-order rate constant (keo) was used to fit propofol concentration-bispectral index (BIS) data. Population modeling analysis was performed by nonlinear mixed effects regression in NONMEM (ICON, Dublin, Ireland). PK data from 3 previous studies in obese adult patients (n = 47), including PD (BIS) data from 1 of these studies (n = 20), were pooled and simultaneously analyzed. A decrease in NONMEM objective function (ΔOBJ) of 3.84 points, for an added parameter, was considered significant at the 0.05 level. In the second step of the study, we analyzed the predictive performance (median predictive errors [MDPE] and median absolute predictive errors [MDAPE]) of the current model and of other available models using an independent data set (n = 14). RESULTS: Step 1: The selected PKPD model produced an adequate fit of the data. Total body weight resulted in the best size scalar for volumes and clearances (ΔOBJ, -18.173). Empirical allometric total body weight relationships did not improve model fit (ΔOBJ, 0.309). A lag time parameter for BIS response improved the fit (ΔOBJ, 89.593). No effect of age or gender was observed. Step 2: Current model MDPE and MDAPE were 11.5% (3.7-25.0) and 26.8% (20.7-32.6) in the PK part and 0.4% (-10.39 to 3.85) and 11.9% (20.7-32.6) in the PD part. The PK model developed by Eleveld et al resulted in the lowest PK predictive errors (MDPE = <10% and MDAPE = <25%). CONCLUSIONS: We derived and validated a propofol PKPD model to perform effect-site TCI in obese patients. This model, derived exclusively from obese patient's data, is not recommended for TCI in lean patients because it carries the risk of underdosing.

Acute effect of iloprost inhalation on right atrial function and ventricular dyssynchrony in patients with pulmonary artery hypertension.

BACKGROUND: Right atrium function and ventricular function have significant prognostic value in pulmonary arterial hypertension patients. Acute changes in right ventricular synchrony and right atrium function postiloprost inhalation have not been evaluated. METHODS: Cross-sectional study. Consecutive pulmonary arterial hypertension patients (group I from Nice classification) were included. Echocardiographic right atrium and right ventricular function pre- and postiloprost inhalation, including a right ventricular dyssynchrony index and right atrium function using speckle tracking, were performed in all patients. RESULTS: Twenty pulmonary arterial hypertension patients, 44±7 years and 90% females, were included. After iloprost inhalation, we observed a significant increment in right ventricular fractional area change and a significant decrease in right ventricular dyssynchrony index (21.4±5.6% vs 26.1±4.0 %, P=.007 and 79±44 vs 32±22 mseconds, P<.01, respectively), also an improvement in right atrium reservoir function (8.6±3.1% vs 11.7±3.5 %, P=.002). CONCLUSIONS: Iloprost inhalation induces acute changes in right ventricular function, dyssynchrony, and right atrium performance that may add relevant clinical information in the management and risk stratification of pulmonary arterial hypertension patients.

[Characteristics, management, and outcomes of illicit drug consumers with acute myocardial infarction]. / Características, manejo y evolución intrahospitalaria de usuarios de drogas ilícitas con infarto agudo del miocardio.

BACKGROUND: Consumption of illicit drugs (ID) has been associated with an increased risk of acute myocardial infarction (AMI). There is limited national evidence about the impact of substance use over the clinical presentation, management and outcomes of AMI patients. AIM: To describe the prevalence of ID consumption in patients within the Chilean Registry of Myocardial Infarction (GEMI), comparing clinical characteristics, management and outcome according to consumption status. MATERIAL AND METHODS: We reviewed data from the GEMI registry between 2001 and 2013, identifying 18,048 patients with AMI. The sample was stratified according to presence or absence of previous ID consumption, comparing different demographic and clinical variables between groups. RESULTS: Two hundred eighty five patients (1.6%) had history of ID consumption (cocaine in 66%, cannabis in 35% and central nervous system stimulants in 24.0%). Compared with non-users, ID consumers were younger, predominantly male and had a lower prevalence of cardiovascular risk factors, except for tobacco smoking (86.3% and 42.5% respectively, p < 0.01). Among consumers, there was a higher percentage of ST segment elevation (85.2% and 67.8% respectively, p < 0.01) and anterior wall AMI (59.9 and 49.5% respectively, p = 0.01). Additionally, they had a higher rate of primary angioplasty (48.8% and 25.5% respectively, p < 0.01). There was no difference in hospital mortality between groups when stratified by age. CONCLUSIONS: A low percentage of patients with AMI had a previous history of ID consumption in our national setting. These patients were younger and had a greater frequency of ST segment elevation AMI, which probably determined a more invasive management.

[Survival of patients with pulmonary arterial hypertension after the advent of specific pulmonary vasodilator therapies]. / Sobrevida a mediano plazo en los pacientes con hipertensión arterial pulmonar en la era de terapias vasodilatadoras específicas del territorio vascular pulmonar.

BACKGROUND: Pulmonary arterial hypertension (PAH) is a rare and progressive disease. Long-term survival remains poor despite of advances in specific vasodilator therapy. AIM: To describe the survival rate in a cohort of PAH patients in two referral centers in Chile. PATIENTS AND METHODS: One hundred fifteen patients aged 43 ± 15.6 years (85% females) with PAH qualified for this study. Their median pulmonary artery pressure was 55.4 ± 14 mmHg and their six minutes walking capacity was 368 ± 119 m. They were followed for 58 ± 0.4 months and their actual survival rates were compared with the estimated survival using the equation proposed by the French registry of PAH. RESULTS: One, two and three year survival rates were 97, 94 and 89%, respectively. The observed survival rates were greater than the estimated survival. CONCLUSIONS: The improvement in survival rates observed in this cohort of patients is similar to what has been described in literature.

Prevalence of seven cardiovascular-related genetic polymorphisms in a Chilean mestizo healthy population.

OBJECTIVE: Among the genetic factors associated with cardiovascular disease (CVD), determining polymorphic genotypes could help to understand the appearance of the illness. Ethnic differences in these polymorphisms could explain population variability in susceptibility to CVD. The main goal of this research is to study the presence of more relevant genetic variants of ApoE, CETP, ACE, PAI-1, MTHFR, FII and FVL of the coagulation cascade, to describe the presence of cardiovascular-related variants in a mestizo group of the Chilean people. METHODS AND RESULTS: The studied population comprised 146 unrelated subjects from the general population, diagnosed as healthy, who were genotyped through conventional and/or real-time PCR. The allele frequencies for the Chilean population were: Apo E, ε2: 0.036, ε3: 0.875 and ε4: 0.089; CETP, B1: 0.51 and B2: 0.49; MTHFR, C: 0.52 and T: 0.48; ACE, I: 0.603 and D: 0.397; PAI-1, 4G: 0.381 and 5G: 0.619; FII, G: 0.97 and A: 0.03, and FV Leiden, G: 0.97 and A: 0.03. CONCLUSIONS: This study contributes to establish a first picture in the Chilean mestizo population about the frequencies of these variants, which could act as single or complementary risk factors to trigger CVD. The obtained allele frequencies show great differences in relation to other South American populations.

[Effect of educational level on the prognosis of acute myocardial infarction]. / Efecto del nivel educacional en la sobrevida posterior a un infarto agudo de miocardio: Registro Chileno de Infarto de Miocardio, GEMI 2009-2012.

BACKGROUND: Socioeconomic status is associated with cardiovascular mortality. AIM: To evaluate the effect of educational level, on the prognosis of patients with acute myocardial infarction in Chile. MATERIAL AND METHODS: Cohort study of 3,636 patients aged 63.1 ± 13.2 years, 27% women, hospitalized in 16 centers participating in the Chilean Myocardial Infarction Registry (GEMI) between 2009 and 2012. Vital status was obtained from the National Mortality Database. Patients were divided, according to educational level, in four groups, namely none (no formal education), basic (< 8 years), secondary (8-12 years) and tertiary (> 12 years). Crude and adjusted (age, sex, cardiovascular risk factors and treatments) hazard ratios (HR) were estimated using Cox regression models. RESULTS: The distribution by educational level was 3.2% none, 31.8% basic, 43.0% secondary and 22.0% tertiary. During a median follow-up period of 22 months (interquartile range 11-37 years), 631 patients died (17.3%), of whom 198 died during hospitalization (5.5%). The 30 day case-fatality rate according to educational level was 3.4% in tertiary, 4.7% in secondary, 11.9% in basic, 19.1% in none (p < 0.0001). Among patients surviving the first 30 days, the case-fatality rate was 4.4%, 8.6%, 14.6% and 27.0%, respectively (p < 0.0001). The increased risk of death for groups with lower education compared with individuals with tertiary education, persisted in the multivariate analysis with a hazard ratio for secondary education 1.58 (95% confidence intervals (CI), 1.18-2.10); for basic education 1.90 (95% CI, 1.41-2.47) and for none 3.50 (95% CI, 2.35-5.21). CONCLUSIONS: A lower educational level was associated with a worse prognosis in patients with myocardial infarction, even after controlling for potential confounding factors.

Effects of trimetazidine in nonischemic heart failure: a randomized study.

OBJECTIVES: Heart failure (HF) is associated with changes in myocardial metabolism that lead to impairment of contractile function. Trimetazidine (TMZ) modulates cardiac energetic efficiency and improves outcomes in ischemic heart disease. We evaluated the effects of TMZ on left ventricular ejection fraction (LVEF), cardiac metabolism, exercise capacity, O2 uptake, and quality of life in patients with nonischemic HF. METHODS AND RESULTS: Sixty patients with stable nonischemic HF under optimal medical therapy were included in this randomized double-blind study. Patients were randomized to TMZ (35 mg orally twice a day) or placebo for 6 months. LVEF, 6-minute walk test (6MWT), maximum O2 uptake in cardiopulmonary exercise test, different markers of metabolism, oxidative stress, and endothelial function, and quality of life were assessed at baseline and after TMZ treatment. Left ventricular peak glucose uptake was evaluated with the use of the maximum standardized uptake value (SUV) by 18-fluorodeoxyglucose positron emission tomography ((18)FDG-PET). Etiology was idiopathic in 85% and hypertensive in 15%. Both groups were similar in age, functional class, LVEF, and levels of N-terminal pro-B-type natriuretic peptide at baseline. After 6 months of TMZ treatment, no changes were observed in LVEF (31 ± 10% vs 34 ± 8%; P = .8), 6MWT (443 ± 25 m vs 506 ± 79 m; P = .03), maximum O2 uptake (19.1 ± 5.0 mL kg(-1) min(-1) vs 23.0 ± 7.2 mL kg(-1) min(-1); P = .11), functional class (percentages of patients in functional classes I/II/III/IV 10/3753/0 vs 7/40/50/3; P = .14), or quality of life (32 ± 26 points vs 24 ± 18 points; P = .25) in TMZ versus placebo, respectively. In the subgroup of patients evaluated with (18)FDG-PET, no significant differences were observed in SUV between both groups (7.0 ± 3.6 vs 8.2 ± 3.4 respectively; P = .47). CONCLUSIONS: In patients with nonischemic HF, the addition of TMZ to optimal medical treatment does not result in significant changes of LVEF, exercise capacity, O2 uptake, or quality of life.

Performance of propofol target-controlled infusion models in the obese: pharmacokinetic and pharmacodynamic analysis.

BACKGROUND: Obesity is associated with important physiologic changes that can potentially affect the pharmacokinetic (PK) and pharmacodynamic (PD) profile of anesthetic drugs. We designed this study to assess the predictive performance of 5 currently available propofol PK models in morbidly obese patients and to characterize the Bispectral Index (BIS) response in this population. METHODS: Twenty obese patients (body mass index >35 kg/m), aged 20 to 60 years, scheduled for laparoscopic bariatric surgery, were studied. Anesthesia was administered using propofol by target-controlled infusion and remifentanil by manually controlled infusion. BIS data and propofol infusion schemes were recorded. Arterial blood samples to measure propofol were collected during induction, maintenance, and the first 2 postoperative hours. Median performance errors (MDPEs) and median absolute performance errors (MDAPEs) were calculated to measure model performance. A PKPD model was developed using NONMEM to characterize the propofol concentration-BIS dynamic relationship in the presence of remifentanil. RESULTS: We studied 20 obese adults (mean weight: 106 kg, range: 85-141 kg; mean age: 33.7 years, range: 21-53 years; mean body mass index: 41.4 kg/m, range: 35-52 kg/m). We obtained 294 arterial samples and analyzed 1431 measured BIS values. When total body weight (TBW) was used as input of patient weight, the Eleveld allometric model showed the best (P < 0.0001) performance with MDPE = 18.2% and MDAPE = 27.5%. The 5 tested PK models, however, showed a tendency to underestimate propofol concentrations. The use of an adjusted body weight with the Schnider and Marsh models improved the performance of both models achieving the lowest predictive errors (MDPE = <10% and MDAPE = <25%; all P < 0.0001). A 3-compartment PK model linked to a sigmoidal inhibitory Emax PD model by a first-order rate constant (ke0) adequately described the propofol concentration-BIS data. A lag time parameter of 0.44 minutes (SE = 0.04 minutes) to account for the delay in BIS response improved the fit. A simulated effect-site target of 3.2 µg/mL (SE = 0.17 µg/mL) was estimated to obtain BIS of 50, in the presence of remifentanil, for a typical patient in our study. CONCLUSIONS: The Eleveld allometric PK model proved to be superior to all other tested models using TBW. All models, however, showed a trend to underestimate propofol concentrations. The use of adjusted body weight instead of TBW with the traditional Schnider and Marsh models markedly improved their performance achieving the lowest predictive errors of all tested models. Our results suggest no relevant effect of obesity on both the time profile of BIS response and the propofol concentration-BIS relationship.

Hybrid Cardiac Rehabilitation Program in a Low-Resource Setting: A Randomized Clinical Trial.

Importance: While effective, cardiovascular rehabilitation (CR) as traditionally delivered is not well implemented in lower-resource settings. Objective: To test the noninferiority of hybrid CR compared with traditional CR in terms of cardiovascular events. Design, Setting, and Participants: This pragmatic, multicenter, parallel arm, open-label randomized clinical trial (the Hybrid Cardiac Rehabilitation Trial [HYCARET]) with blinded outcome assessment was conducted at 6 referral centers in Chile. Adults aged 18 years or older who had a cardiovascular event or procedure, no contraindications to exercise, and access to a mobile telephone were eligible and recruited between April 1, 2019, and March 15, 2020, with follow-up until July 29, 2021. Interventions: Participants were randomized 1:1 in permuted blocks to the experimental arm, which received 10 center-based supervised exercise sessions plus counseling in 4 to 6 weeks and then were supported at home via telephone calls and text messages through weeks 8 to 12, or the control arm, which received the standard CR of 18 to 22 sessions with exercises and education in 8 to 12 weeks. Main Outcomes and Measures: The primary outcome was cardiovascular events or mortality. Secondary outcomes were quality of life, return to work, and lifestyle behaviors measured with validated questionnaires; muscle strength and functional capacity, measured through physical tests; and program adherence and exercise-related adverse events, assessed using checklists. Results: A total of 191 participants were included (mean [SD] age, 58.74 [9.80] years; 145 [75.92%] male); 93 were assigned to hybrid CR and 98 to standard CR. At 1 year, events had occurred in 5 unique participants in the hybrid CR group (5.38%) and 9 in the standard CR group (9.18%). In the intention-to-treat analysis, the hybrid CR group had 3.80% (95% CI, -11.13% to 3.52%) fewer cardiovascular events than the standard CR group, and relative risk was 0.59 (95% CI, 0.20-1.68) for the primary outcome. In the per-protocol analysis at different levels of adherence to the intervention, all 95% CIs crossed the noninferiority boundary (eg, 20% adherence: absolute risk difference, -0.35% [95% CI, -7.56% to 6.85%]; 80% adherence: absolute risk difference, 3.30% [95% CI, -3.70% to 10.31%]). No between-group differences were found for secondary outcomes except adherence to supervised CR sessions (79.14% [736 of 930 supervised sessions] in the hybrid CR group vs 61.46% [1201 of 1954 sessions] in the standard CR group). Conclusions and Relevance: The results suggest that a hybrid CR program is noninferior to standard center-based CR in a low-resource setting, primarily in terms of recurrent cardiovascular events and potentially in terms of intermediate outcomes. Hybrid CR may induce superior adherence to supervised exercise. Clinical factors and patient preferences should inform CR model allocation. Trial Registration: ClinicalTrials.gov Identifier: NCT03881150.