Clinical development and proof of principle testing of new regenerative vascular endothelial growth factor-D therapy for refractory angina: rationale and design of the phase 2 ReGenHeart trial.

BACKGROUND: Despite tremendous therapeutic advancements, a significant proportion of coronary artery disease patients suffer from refractory angina pectoris, that is, quality-of-life-compromising angina that is non-manageable with established pharmacological and interventional treatment options. Adenoviral vascular endothelial growth factor-DΔNΔC (AdVEGF-D)-encoding gene therapy (GT) holds promise for the treatment of refractory angina. METHODS: ReGenHeart is an investigator-initiated, multicentre, randomised, placebo-controlled and double-blinded phase 2 clinical trial that aims to study the safety and efficacy of intramyocardially administered angiogenic AdVEGF-D GT for refractory angina. Patients will be randomised in a 2:1 ratio and blocks of six to receive either AdVEGF-D or placebo. Primary endpoints are improvements in functional capacity assessed with the 6 min walking test and angina symptoms with Canadian Cardiovascular Society class after 6 month follow-up. Secondary endpoints are improvements in myocardial perfusion assessed with either positron emission tomography or single-photon emission CT after 6 month follow-up and functional capacity and angina symptoms after 12 months. In addition, changes in the quality of life, the use of angina medication and the incidence of major adverse cardiac and cerebrovascular events will be evaluated. CONCLUSIONS: The phase 2 ReGenHeart trial will provide knowledge of the safety and efficacy of AdVEGF-D GT to ameliorate symptoms in refractory angina patients, extending and further testing positive results from the preceding phase 1/2a trial.

Ramipril After Transcatheter Aortic Valve Implantation in Patients Without Reduced Ejection Fraction: The RASTAVI Randomized Clinical Trial.

BACKGROUND: Patients with aortic stenosis may continue to have an increased risk of heart failure, arrhythmias, and death after successful transcatheter aortic valve implantation. Renin-angiotensin system inhibitors may be beneficial in this setting. We aimed to explore whether ramipril improves the outcomes of patients with aortic stenosis after transcatheter aortic valve implantation. METHODS AND RESULTS: PROBE (Prospective Randomized Open, Blinded Endpoint) was a multicenter trial comparing ramipril with standard care (control) following successful transcatheter aortic valve implantation in patients with left ventricular ejection fraction >40%. The primary end point was the composite of cardiac mortality, heart failure readmission, and stroke at 1-year follow-up. Secondary end points included left ventricular remodeling and fibrosis. A total of 186 patients with median age 83 years (range 79-86), 58.1% women, and EuroSCORE-II 3.75% (range 3.08-4.97) were randomized to receive either ramipril (n=94) or standard treatment (n=92). There were no significant baseline, procedural, or in-hospital differences. The primary end point occurred in 10.6% in the ramipril group versus 12% in the control group (P=0.776), with no differences in cardiac mortality (ramipril 1.1% versus control group 2.2%, P=0.619) but lower rate of heart failure readmissions in the ramipril group (3.2% versus 10.9%, P=0.040). Cardiac magnetic resonance analysis demonstrated better remodeling in the ramipril compared with the control group, with greater reduction in end-systolic and end-diastolic left ventricular volumes, but nonsignificant differences were found in the percentage of myocardial fibrosis. CONCLUSIONS: Ramipril administration after transcatheter aortic valve implantation in patients with preserved left ventricular function did not meet the primary end point but was associated with a reduction in heart failure re-admissions at 1-year follow-up. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique Identifier: NCT03201185.

One-year longitudinal changes of peripheral CD4+ T-lymphocyte counts, gut microbiome, and plaque vulnerability after an acute coronary syndrome.

Background: Longitudinal changes in gut microbiome and inflammation may be involved in the evolution of atherosclerosis after an acute coronary syndrome (ACS). We aimed to characterize repeated profiles of gut microbiota and peripheral CD4+ T lymphocytes during the first year after an ACS, and to address their relationship with atherosclerotic plaque changes. Methods: Over one year we measured the microbiome, peripheral counts of CD4+ T populations and cytokines in 67 patients shortly after a first ACS. We compared baseline measurements to those of a matched population of 40 chronic patients. A subgroup of 20 ACS patients underwent repeated assessment of fibrous cap thickness (FCT) of a non-culprit lesion. Results: At admission, ACS patients showed gut dysbiosis compared with the chronic group, which was rapidly reduced and remained low at 1-year. Also, their Th1 and Th2 CD4+ T counts were increased but decreased over time. The CD4+ T counts were related to ongoing changes in gut microbiome. Unsupervised clustering of repeated CD4+ Th0, Th1, Th2, Th17 and Treg counts in ACS patients identified two different cell trajectory patterns, related to cytokines. The group of patients following a high-CD4+ T cell trajectory showed a one-year reduction in their FCT [net effect = -24.2 µm; p = 0.016]. Conclusions: Patients suffering an ACS show altered profiles of microbiome and systemic inflammation that tend to mimic values of chronic patients after 1-year. However, in one-third of patients, this inflammatory state remains particularly dysregulated. This persistent inflammation is likely related to plaque vulnerability as evident by fibrous cap thinning (Clinical Trial NCT03434483).

Stasis imaging predicts the risk of cardioembolic events related to acute myocardial infarction: the ISBITAMI study.

INTRODUCTION AND OBJECTIVES: In the setting of ST-segment elevation myocardial infarction (STEMI), imaging-based biomarkers could be useful for guiding oral anticoagulation to prevent cardioembolism. Our objective was to test the efficacy of intraventricular blood stasis imaging for predicting a composite primary endpoint of cardioembolic risk during the first 6 months after STEMI. METHODS: We designed a prospective clinical study, Imaging Silent Brain Infarct in Acute Myocardial Infarction (ISBITAMI), including patients with a first STEMI, an ejection fraction ≤ 45% and without atrial fibrillation to assess the performance of stasis metrics to predict cardioembolism. Patients underwent ultrasound-based stasis imaging at enrollment followed by heart and brain magnetic resonance at 1-week and 6-month visits. From the stasis maps, we calculated the average residence time, RT, of blood inside the left ventricle and assessed its performance to predict the primary endpoint. The longitudinal strain of the 4 apical segments was quantified by speckle tracking. RESULTS: A total of 66 patients were assigned to the primary endpoint. Of them, 17 patients had 1 or more events: 3 strokes, 5 silent brain infarctions, and 13 mural thromboses. No systemic embolisms were observed. RT (OR, 3.73; 95%CI, 1.75-7.9; P<.001) and apical strain (OR, 1.47; 95%CI, 1.13-1.92; P=.004) showed complementary prognostic value. The bivariate model showed a c-index=0.86 (95%CI, 0.73-0.95), a negative predictive value of 1.00 (95%CI, 0.94-1.00), and positive predictive value of 0.45 (95%CI, 0.37-0.77). The results were confirmed in a multiple imputation sensitivity analysis. Conventional ultrasound-based metrics were of limited predictive value. CONCLUSIONS: In patients with STEMI and left ventricular systolic dysfunction in sinus rhythm, the risk of cardioembolism may be assessed by echocardiography by combining stasis and strain imaging. Registered at ClinicalTrials.gov (NCT02917213).

Impact of the Mediterranean Diet on the Gut Microbiome of a Well-Defined Cohort of Healthy Individuals.

A comprehensive understanding of gut microbiota in a clearly defined group of healthy individuals is essential when making meaningful comparisons with various diseases. The Mediterranean diet (MD), renowned for its potential health benefits, and the influence of adherence thereto on gut microbiota have become a focus of research. Our aim was to elucidate the impact of adherence to the MD on gut microbiota composition in a well-defined cohort. In this prospective study, healthy volunteers completed a questionnaire to provide demographic data, medical history, and dietary intake. Adherence was evaluated using the Med-DQI. The V4 region of the 16S rRNA gene was sequenced. Analysis of sequencing data and statistical analysis were performed using MOTHUR software and R. The study included 60 patients (51.7% females). Adherence correlated with alpha diversity, and higher values were recorded in good adherers. Good adherers had a higher abundance of Paraprevotella and Bacteroides (p < 0.001). Alpha diversity correlated inversely with fat intake and positively with non-starch polysaccharides (NSPs). Evenness correlated inversely with red meat intake and positively with NSPs. Predicted functional analysis highlighted metabolic pathway differences based on adherence to the MD. In conclusion, our study adds useful information on the relationship between the MD and the gut microbiome.

Cannon A wave validation as a diagnostic tool in paroxysmal supraventricular tachycardias.

OBJECTIVE: The presence of cannon A waves, the so called "frog sign", has traditionally been considered diagnostic of atrioventricular nodal re-entrant tachycardia (AVNRT). Nevertheless, it has never been systematically evaluated. The aim of this study is to assess the independent diagnostic utility of cannon A waves in the differential diagnosis of supraventricular tachycardias (SVTs). METHODS: We prospectively included 100 patients who underwent an electrophysiology (EP) study for SVT. The right jugular venous pulse was recorded during the study. In 61 patients, invasive central venous pressure (CVP) was registered as well. CVP increase is thought to be related with the timing between atria and ventricle depolarization; two groups were prespecified, the short VA interval tachycardias (including typical AVNRT and atrioventricular reciprocating tachycardia (AVRT) mediated by a septal accessory pathway) and the long VA interval tachycardias (including atypical AVNRT and AVRT mediated by a left free wall accessory pathway). RESULTS: The relationship between cannon A waves and AVNRT did not reach the statistical significance (OR: 3.01; p = .058); On the other hand, it was clearly associated with the final diagnosis of a short VA interval tachycardia (OR: 10.21; p < .001). CVP increase showed an inversely proportional relationship with the VA interval during tachycardia (b = -.020; p < .001). CVP increase was larger in cases of AVNRT (4.0 mmHg vs. 1.2 mmHg; p < .001) and short VA interval tachycardias (3.9 mmHg vs. 1.2 mmHg; p < .001). CONCLUSION: The presence of cannon A waves is associated with the final diagnosis of short VA interval tachycardias.

Increased Chamber Resting Tone Is a Key Determinant of Left Ventricular Diastolic Dysfunction.

BACKGROUND: Twitch-independent tension has been demonstrated in cardiomyocytes, but its role in heart failure (HF) is unclear. We aimed to address twitch-independent tension as a source of diastolic dysfunction by isolating the effects of chamber resting tone (RT) from impaired relaxation and stiffness. METHODS: We invasively monitored pressure-volume data during cardiopulmonary exercise in 20 patients with hypertrophic cardiomyopathy, 17 control subjects, and 35 patients with HF with preserved ejection fraction. To measure RT, we developed a new method to fit continuous pressure-volume measurements, and first validated it in a computational model of loss of cMyBP-C (myosin binding protein-C). RESULTS: In hypertrophic cardiomyopathy, RT (estimated marginal mean [95% CI]) was 3.4 (0.4-6.4) mm Hg, increasing to 18.5 (15.5-21.5) mm Hg with exercise (P<0.001). At peak exercise, RT was responsible for 64% (53%-76%) of end-diastolic pressure, whereas incomplete relaxation and stiffness accounted for the rest. RT correlated with the levels of NT-proBNP (N-terminal pro-B-type natriuretic peptide; R=0.57; P=0.02) and with pulmonary wedge pressure but following different slopes at rest and during exercise (R2=0.49; P<0.001). In controls, RT was 0.0 mm Hg and 1.2 (0.3-2.8) mm Hg in HF with preserved ejection fraction patients and was also exacerbated by exercise. In silico, RT increased in parallel to the loss of cMyBP-C function and correlated with twitch-independent myofilament tension (R=0.997). CONCLUSIONS: Augmented RT is the major cause of LV diastolic chamber dysfunction in hypertrophic cardiomyopathy and HF with preserved ejection fraction. RT transients determine diastolic pressures, pulmonary pressures, and functional capacity to a greater extent than relaxation and stiffness abnormalities. These findings support antimyosin agents for treating HF.

Complications and inappropriate shocks in pediatric patients receiving a subcutaneous implantable cardioverter defibrilator.

INTRODUCTION AND OBJECTIVES: There is limited evidence regarding the use of subcutaneous implantable cardioverter-defibrillators (S-ICD) in pediatric patients. The aim of this study was to determine the incidence of complications in these patients at our center, according to the type of ICD and patient size. METHODS: We included all patients aged<18 years who received an S-ICD since 2016 at our center. As a control group, we also included contemporary patients (since 2014) who received a transvenous ICD (TV-ICD). The primary endpoint was a composite of complications and inappropriate shocks. RESULTS: A total of 26 patients received an S-ICD (median age, 14 [5-17] years; body mass index [BMI], 20.2 kg/m2). Implantation was intermuscular in 23 patients (88%) and subserratus in the remainder. Two incisions were used in 24 patients (92%). In all patients, 2 zones were programmed: a conditional zone set at 230 (220-230) bpm, and a shock zone set at 250 bpm. Nineteen patients received a TV-ICD (median age, 11 [range, 5-16] years; BMI, 19.2 kg/m2, 79% single-chamber). Survival free from the primary endpoint at 5 years was 80% in the S-ICD group and 63% in the TV-ICD group (P=.54). Survival free from inappropriate shocks was similar (85% vs 89%, P=.86), while survival free from complications was higher in the S-ICD group (96% vs 57%, cloglog P=.016). There were no therapy failures in the S-ICD group, and no increased complication rates were observed in patients with BMI ≤20 kg/m2. CONCLUSIONS: With contemporary implantation techniques and programming, S-ICD is a safe and effective therapy in pediatric patients. The number of inappropriate shocks is similar to TV-ICD, with fewer short- and mid-term complications.

Systematic influenza screening in cardiac intensive care units during the influenza season: A prospective study in Spain.

BACKGROUND: Little is known about the incidence of influenza among admissions to the cardiac intensive care unit (C-ICU), accuracy of clinical suspicion, and influenza vaccination uptake. We evaluated the incidence of influenza at C-ICU admission during the influenza season, potential underdiagnosis, and vaccination uptake. METHODS: Prospective study at five C-ICUs during the 2017-2020 influenza seasons. A nasopharyngeal swab was collected at admission from patients who consented (n = 788). Testing was with Xpert®XpressFlu/RSV. RESULTS: Influenza was detected in 43 patients (5.5%) (40 FluA; 3 FluB) and clinically suspected in 27 (62.8%). Compared to patients without influenza, patients with influenza more frequently had heart failure (37.2% vs 22.8%, P = 0.031), previous contact with relatives with influenza-like illnesses (23.3% vs 12.5%, P = 0.042), antimicrobial use (67.4% vs 23.2%, P <0.01), and need for mechanical ventilation (25.6% vs 14.5%, P = 0.048). Patients received oseltamivir promptly. We found no differences in mortality (11.6% vs 5.2%, P = 0.076). Patients with influenza more frequently had myocarditis (9.3% vs 0.9%, P <0.01) and pericarditis (7.0% vs 0.8%, P = 0.01). Overall, 43.0% of patients (339/788) were vaccinated (51.9% of those with a clear indication [303/584]). CONCLUSION: Influenza seems to be a frequently underdiagnosed underlying condition in admissions to the C-ICU. Influenza should be screened for at C-ICU admission during influenza epidemics.

Clinical outcomes of TAVI with the Myval balloon-expandable valve for non-calcified aortic regurgitation.

BACKGROUND: Transcatheter aortic valve replacement (TAVR) in non-calcified aortic regurgitation (NCAR) is an off-label procedure. The balloon-expandable Myval includes extra-large sizes (30.5 mm and 32 mm) of interest in this setting. AIMS: We aimed to evaluate the safety and feasibility of Myval in NCAR. METHODS: This was an international, multicentre, observational study that enrolled all consecutive patients with symptomatic severe NCAR undergoing TAVR with the Myval device. The images were centrally analysed. RESULTS: A total of 113 patients were recruited, 64.6% were men, the mean age was 78.4±7.5 years, and the Society of Thoracic Surgeons score was 2.7±1.7%. Aortic root dilatation was present in 59.3% of patients, 7.1% were bicuspid, and the mean annular area was 638.6±106.0 mm2. The annular area was beyond the recommended range for extra-large sizes in 2.6% of cases, and additional volume was added in 92% (median 4 cc, up to 9 cc). The extra-large sizes were used in 95 patients (84.1%), and the mean oversizing was 17.9±11.0%. The technical success rate was 94.7%; the rate of residual ≥moderate aortic regurgitation was 8.9%, and the pacemaker rate was 22.2%. There were no cases of annular rupture, cardiac tamponade, or aortic dissection, but in 4 patients (3.5%) valve embolisation occurred (1 antegrade and 3 ventricular), all in cases with a tapered left ventricle outflow tract (p=0.007). Thirty-day and 1-year mortality were 5.3% and 9.7%, respectively. Technical success was associated with better survival (97.1% vs 72.7%; p=0.012), and valve embolisation was the main determinant of mortality (p=0.047). CONCLUSIONS: Myval is a feasible and safe option for selected non-operable patients with NCAR and demonstrated good midterm outcomes and lack of impact of oversizing on device durability.

Changes in circulating ApoJ-Glyc levels in patients with suspected acute coronary syndrome: The EDICA trial.

BACKGROUND: Myocardial ischemia induces intracellular accumulation of non-glycosylated apolipoprotein J that results in a reduction of circulating glycosylated ApoJ (ApoJ-Glyc). The latter has been suggested to be a marker of transient myocardial ischemia. OBJECTIVE: This proof-of-concept clinical study aimed to assess whether changes in circulating ApoJ-Glyc could detect myocardial ischemia in patients attending the emergency department (ED) with chest pain suggestive of acute coronary syndrome (ACS). METHODS: In suspected ACS patients, EDICA (Early Detection of Myocardial Ischemia in Suspected Acute Coronary Syndromes by ApoJ-Glyc a Novel Pathologically based Ischemia Biomarker), a multicentre, international, cohort study assessed changes in 2 glycosylated variants of ApoJ-Glyc, (ApoJ-GlycA2 and ApoJ-GlycA6), in serum samples obtained at ED admission (0 h), and 1 h and 3 h thereafter, blinded to the clinical diagnosis (i.e. STEMI, NSTEMI, unstable angina, non-ischemic). RESULTS: 404 patients were recruited; 291 were given a clinical diagnosis of "non-ischemic" chest pain and 113 were considered to have had an ischemic event. ApoJ-GlycA6 was lower on admission in ischemic compared with "non-ischemic" patients (66 [46-90] vs. 73 [56-95] µg/ml; P = 0.04). 74% of unstable angina patients (all with undetectable hs-Tn), had ischemic changes in ApoJ-Glyc at 0 h and 89% at 1 h. Initially low ApoJ-Glyc levels in 62 patients requiring coronary revascularization increased significantly after successful percutaneous intervention. CONCLUSIONS: Circulating ApoJ-Glyc concentrations decrease early in ED patients with myocardial ischemia compared with "non-ischemic" patients, even in the absence of troponin elevations. ApoJ-Glyc may be a useful marker of myocardial ischemia in the ED setting.

Prognostic Implications of High-Degree Atrio-Ventricular Block in Patients with Acute Myocardial Infarction in the Contemporary Era.

BACKGROUND: High-degree atrioventricular block (HAVB) is a known complication of ST-segment elevation myocardial infarction (STEMI). We aimed to determine the prevalence and prognostic impact of HAVB in a contemporary cohort of STEMI. METHODS: Data were collected from the DIAMANTE registry that included STEMI patients admitted to our cardiac intensive care unit treated with urgent reperfusion. We studied the clinical characteristics and evolution in patients with and without HAVB at admission. RESULTS: From 1109 consecutive patients, HAVB was documented in 95 (8.6%). The right coronary artery was the culprit vessel in 84 patients with HAVB (88.4%). The independent predictors of HAVB were: male sex (OR 1.9, 95% CI 1.2-2.9), age (OR 1.03, 95% CI 1.01-1.05), involvement of right coronary artery (OR 12.4, 95% CI 7.6-20.2), and creatinine value (OR 1.5, 95% CI 1.1-2.0). A transient percutaneous pacemaker was used in 37 patients with HAVB (38.9%). Patients with HAVB had higher mortality that patients without HAVB (15.8% vs. 4.1%, p < 0.001); however, in multivariate analysis, HAVB was not an independent predictor of in-hospital mortality. CONCLUSIONS: HAVB was seen in 9% of STEMI patients and was particularly frequent in elderly males with renal failure. Patients with HAVB had a poor prognosis during hospitalization, but HAVB was not an independent predictor of in-hospital mortality.

Bayesian analysis of the Substrate Ablation vs. Antiarrhythmic Drug Therapy for Symptomatic Ventricular Tachycardia trial.

BACKGROUND AND AIMS: Bayesian analyses can provide additional insights into the results of clinical trials, aiding in the decision-making process. We analysed the Substrate Ablation vs. Antiarrhythmic Drug Therapy for Symptomatic Ventricular Tachycardia (SURVIVE-VT) trial using Bayesian survival models. METHODS AND RESULTS: The SURVIVE-VT trial randomized patients with ischaemic cardiomyopathy and monomorphic ventricular tachycardia (VT) to catheter ablation or antiarrhythmic drugs (AAD) as a first-line strategy. The primary outcome was a composite of cardiovascular death, appropriate implantable cardioverter-defibrillator shocks, unplanned heart failure hospitalizations, or severe treatment-related complications. We used informative, skeptical, and non-informative priors with different probabilities of large effects to compute the posterior distributions using Markov Chain Monte Carlo methods. We calculated the probabilities of hazard ratios (HR) being <1, <0.9, and <0.75, as well as 2-year survival estimates. Of the 144 randomized patients, 71 underwent catheter ablation and 73 received AAD. Regardless of the prior, catheter ablation had a >98% probability of reducing the primary outcome (HR < 1) and a >96% probability of achieving a reduction of >10% (HR < 0.9). The probability of a >25% (HR < 0.75) reduction of treatment-related complications was >90%. Catheter ablation had a high probability (>93%) of reducing incessant/slow undetected VT/electric storm, unplanned hospitalizations for ventricular arrhythmias, and overall cardiovascular admissions > 25%, with absolute differences of 15.2%, 21.2%, and 20.2%, respectively. CONCLUSION: In patients with ischaemic cardiomyopathy and VT, catheter ablation as a first-line therapy resulted in a high probability of reducing several clinical outcomes compared to AAD. Our study highlights the value of Bayesian analysis in clinical trials and its potential for guiding treatment decisions. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT03734562.

Coronary Artery Disease and Prognosis of Heart Failure with Reduced Ejection Fraction.

Our aim was to determine the prognostic impact of coronary artery disease (CAD) on heart failure with reduced ejection fraction (HFrEF) mortality and readmissions. From a prospective multicenter registry that included 1831 patients hospitalized due to heart failure, 583 had a left ventricular ejection fraction of <40%. In total, 266 patients (45.6%) had coronary artery disease as main etiology and 137 (23.5%) had idiopathic dilated cardiomyopathy (DCM), and they are the focus of this study. Significant differences were found in Charlson index (CAD 4.4 ± 2.8, idiopathic DCM 2.9 ± 2.4, p < 0.001), and in the number of previous hospitalizations (1.1 ± 1, 0.8 ± 1.2, respectively, p = 0.015). One-year mortality was similar in the two groups: idiopathic DCM (hazard ratio [HR] = 1), CAD (HR 1.50; 95% CI 0.83-2.70, p = 0.182). Mortality/readmissions were also comparable: CAD (HR 0.96; 95% CI 0.64-1.41, p = 0.81). Patients with idiopathic DCM had a higher probability of receiving a heart transplant than those with CAD (HR 4.6; 95% CI 1.4-13.4, p = 0.012). The prognosis of HFrEF is similar in patients with CAD etiology and in those with idiopathic DCM. Patients with idiopathic DCM were more prone to receive heart transplant.

Prevalence and prognosis of anxiety, insomnia, and type D personality in patients with myocardial infarction: A Spanish cohort.

BACKGROUND: It has been suggested that patients with myocardial infarction and non-obstructive coronary arteries (MINOCA) have more psycho-emotional disorders than patients with obstructive coronary artery disease (MICAD). The aim of this study is to compare the prevalence of anxiety, insomnia, and type D personality between MINOCA and MICAD and their impact on prognosis. METHODS: Patients with myocardial infarction undergoing coronary angiography were prospectively enrolled. Psychological questionnaires were completed by each patient during admission. RESULTS: Among a total of 533 patients, 56 had MINOCA and 477 had MICAD. There were no differences in the prevalence of anxiety and insomnia between both groups: trait anxiety median value (M) MINOCA = 18 (11-34) vs. MICAD M = 19 (12-27), p = 0.8; state anxiety MINOCA M = 19 (11-29) vs. MICAD M = 19 (12.2-26), p = 0.6; and insomnia MINOCA M = 7 (3-11) vs. MICAD M = 7 (3-12), p = 0.95. More MINOCA patients had type D personality (45.0% vs. 28.5%, p = 0.03). At 3-year follow-up, there were no differences in mortality between MINOCA and MICAD (hazard ratio [HR] 0.78, 95% confidence interval [CI] 0.28-2.17) in major adverse cerebral or cardiovascular events (MACCE) (HR 0.71, 95% CI 0.38-1.31). Scores of trait anxiety and negative affectivity were significantly associated with MACCE (HR 1.65, 95% CI [1.05-2.57]; HR 1.75, 95% CI [1.11-2.77], respectively). High insomnia levels were associated with greater mortality (HR 2.72, 95% CI [1.12-6.61]). CONCLUSIONS: Anxiety and insomnia levels were similar between patients with MINOCA and those with MICAD, whilst the prevalence of type D personality was higher in the MINOCA than in the MICAD group. Higher scores in trait anxiety, insomnia, and negative affectivity were related to a worse prognosis at 3-year follow-up.

Nosocomial Infections in Adult Patients Supported by Extracorporeal Membrane Oxygenation in a Cardiac Intensive Care Unit.

The use of venoarterial (VA) extracorporeal membrane oxygenation therapy (ECMO) in patients admitted to cardiac intensive care units (CICU) has increased. Data regarding infections in this population are scarce. In this retrospective study, we analyzed the risk factors, outcome, and predictors of in-hospital mortality due to nosocomial infections in patients with ECMO admitted to a single coronary intensive care unit between July 2013 and March 2019 treated with VA-ECMO for >48 h. From 69 patients treated with VA-ECMO >48 h, (median age 58 years), 29 (42.0%) patients developed 34 episodes of infections with an infection rate of 0.92/1000 ECMO days. The most frequent were ventilator-associated pneumonia (57.6%), tracheobronchitis (9.1%), bloodstream infections (9.1%), skin and soft tissue infections (9.1%), and cytomegalovirus reactivation (9.1%). In-hospital mortality was 47.8%, but no association with nosocomial infections was found (p = 0.75). The number of days on ECMO (OR 1.14, 95% CI 1.01-1.30, p = 0.029) and noninfectious complications were higher in the infected patients (OR: 3.8 95% CI = 1.05-14.1). A higher baseline creatinine value (OR: 8.2 95% CI = 1.12-60.2) and higher blood lactate level at 4 h after ECMO initiation (OR: 2.0 95% CI = 1.23-3.29) were significant and independent risk factors for mortality. Conclusions: Nosocomial infections in medical patients treated with VA-ECMO are very frequent, mostly Gram-negative respiratory infections. Preventive measures could play an important role for these patients.

Off-Hours versus Regular-Hours Implantation of Peripheral Venoarterial Extracorporeal Membrane Oxygenation in Patients with Cardiogenic Shock.

BACKGROUND: The "weekend effect" has been associated with worse clinical outcomes. Our aim was to compare off-hours vs. regular-hours peripheral venoarterial extracorporeal membrane oxygenation (VA-ECMO) in cardiogenic shock patients. METHODS: We analyzed in-hospital and 90-day mortality among 147 consecutive patients treated with percutaneous VA-ECMO for medical reasons between July 1, 2013, and September 30, 2022, during regular-hours (weekdays 8:00 a.m.-10:00 p.m.) and off-hours (weekdays 10:01 p.m.-7:59 a.m., weekends, and holidays). RESULTS: The median patient age was 56 years (interquartile range [IQR] 49-64 years) and 112 (72.6%) were men. The median lactate level was 9.6 mmol/L (IQR 6.2-14.8 mmol/L) and 136 patients (92.5%) had a Society for Cardiovascular Angiography and Interventions (SCAI) stage D or E. Cannulation was performed off-hours in 67 patients (45.6%). In-hospital mortality was similar in off-hours and regular hours (55.2% vs. 56.3%, p = 0.901), as was the 90-day mortality (58.2% vs. 57.5%, p = 0.963), length of hospital stay (31 days [IQR 16-65.8 days] vs. 32 days [IQR 18-63 days], p = 0.979), and VA-ECMO related complications (77.6% vs. 70.0%, p = 0.305). CONCLUSIONS: Off-hours and regular-hours percutaneous VA-ECMO implantation in cardiogenic shock of medical cause have similar results. Our results support well-designed 24/7 VA-ECMO implantation programs for cardiogenic shock patients.

Machine Learning to Optimize the Echocardiographic Follow-Up of Aortic Stenosis.

BACKGROUND: Disease progression in patients with mild-to-moderate aortic stenosis is heterogenous and requires periodic echocardiographic examinations to evaluate severity. OBJECTIVES: This study sought to explore the use of machine learning to optimize aortic stenosis echocardiographic surveillance automatically. METHODS: The study investigators trained, validated, and externally applied a machine learning model to predict whether a patient with mild-to-moderate aortic stenosis will develop severe valvular disease at 1, 2, or 3 years. Demographic and echocardiographic patient data to develop the model were obtained from a tertiary hospital consisting of 4,633 echocardiograms from 1,638 consecutive patients. The external cohort was obtained from an independent tertiary hospital, consisting of 4,531 echocardiograms from 1,533 patients. Echocardiographic surveillance timing results were compared with the European and American guidelines echocardiographic follow-up recommendations. RESULTS: In internal validation, the model discriminated severe from nonsevere aortic stenosis development with an area under the receiver-operating characteristic curve (AUC-ROC) of 0.90, 0.92, and 0.92 for the 1-, 2-, or 3-year interval, respectively. In external application, the model showed an AUC-ROC of 0.85, 0.85, and 0.85, for the 1-, 2-, or 3-year interval. A simulated application of the model in the external validation cohort resulted in savings of 49% and 13% of unnecessary echocardiographic examinations per year compared with European and American guideline recommendations, respectively. CONCLUSIONS: Machine learning provides real-time, automated, personalized timing of next echocardiographic follow-up examination for patients with mild-to-moderate aortic stenosis. Compared with European and American guidelines, the model reduces the number of patient examinations.