Twelve-year trends in unprotected left main coronary artery occlusion: insights from a real-world multicentre study.

AIMS: Acute myocardial infarction (AMI) resulting from unprotected left main coronary artery (LMCA) occlusion and subtotal occlusion is a life-threatening condition. Although AMI management has improved in the past two decades, there is limited information on recent trends in patient characteristics, management, and outcomes for acute unprotected LMCA-related AMI. This study aims to assess such trends over a 12 year period. METHODS AND RESULTS: This retrospective multicentre study includes patients with unprotected LMCA occlusion/subtotal occlusion admitted to three tertiary hospitals between 2008 and 2020. The patients were divided into two groups based on the chronology of presentation: a 'past group' (January 2008 to December 2014) and a 'contemporary group' (January 2015 to December 2020). The study compares clinical characteristics, management approaches, and outcomes between the two groups. The study includes 128 patients, with 51 (40%) in the 'past group' and 77 (60%) in the 'contemporary group'. Baseline risk factors did not show statistically significant differences between the two groups, except for hypertension (49% vs. 74%; P = 0.005). Chest pain was more frequent in the 'past group' (98% vs. 89%; P = 0.014), and a trend towards more cardiac arrests was observed in the 'contemporary group' (18% vs. 31%; P = 0.087). Revascularization type did not differ significantly (P = 0.419), but manual thrombectomy was less frequently used (41% vs. 23%; P = 0.032) and stent implantation showed a trend towards higher rates (66% vs. 78%; P = 0.150) in the 'contemporary cohort'. There was a gradual shift from bare-metal to drug-eluting stents, with a significantly higher percentage of ticagrelor/prasugrel loading in the 'contemporary cohort' (5% vs. 79%; P < 0.001). The use of mechanical circulatory support (MCS), although not statistically significant, was higher among patients in the 'past group' (67% vs. 51%; P = 0.073). The type of MCS differed significantly between groups, with a decrease in intra-aortic balloon pump use (67% vs. 42%; P = 0.005) and an increase in veno-arterial extracorporeal membrane oxygenation (4% vs. 22%; P = 0.005) and Impella system (0% vs. 3%) over time. Survival analysis showed no significant differences (P = 0.599; log-rank test) in all-cause mortality between the different time groups, with the long-term survival rate being approximately 30%. CONCLUSIONS: In our real-world population, despite the progressive use of newer drugs and more advanced devices over time, patients with unprotected LMCA occlusion/subtotal occlusion remain a subpopulation with poor prognosis.

ST-Segment Elevation: An Unexpected Culprit.

The clinical presentation of pulmonary embolism (PE) and acute coronary syndrome can be similar. We report a case of a patient presenting with antero-septal ST-segment elevation after cardiac arrest, found to have acute-PE-mimicking ST-segment elevation myocardial infarction (STEMI), treated with aspiration thrombectomy and catheter-directed thrombolysis (CDT). A 78-year-old man was admitted with dyspnea, chest pain and tachycardia. During evaluation, cardiac arrest in pulseless electrical activity was documented. Advanced life support was started immediately. ECG post-ROSC revealed ST-segment elevation in V1-V4 and aVR. Echocardiography showed normal left ventricular function but right ventricular (RV) dilation and severe dysfunction. The patient was in shock and was promptly referred to cardiac catheterization that excluded significant CAD. Due to the discordant ECG and echocardiogram findings, acute PE was suspected, and immediate invasive pulmonary angiography revealed bilateral massive pulmonary embolism. Successful aspiration thrombectomy was performed followed by local alteplase infusion. At the end of the procedure, mPAP was reduced and blood pressure normalized allowing withdrawal of vasopressor support. Twenty-four-hour echocardiographic reassessment showed normal-sized cardiac chambers with preserved biventricular systolic function. Bedside echocardiography in patients with ST-segment elevation post-ROSC is instrumental in raising the suspicion of acute PE. In the absence of a culprit coronary lesion, prompt pulmonary angiography should be considered if immediately feasible. In these cases, CDT and aspiration in high-risk acute PE seem safe and effective in relieving obstructive shock and restoring hemodynamics.

"(Pseudo)cavities inside the heart: What may they unfold?"

Subvalvular aortic stenosis manifesting as a subaortic membrane predisposes to bacterial endocarditis, which typically affects the aortic valve (AoV) or, less frequently, the left ventricular outflow tract (LVOT). We present the case of a 60-year-old woman expressing an odd form of a subvalvular aortic membrane in conjunction with a left Valsalva sinus pseudoaneurysm as a result of an endocarditis complication.

Ticagrelor Loading on ST-Elevation Myocardial Infarction: Interaction With Prodromal Angina on Infarct Size and Clinical Events.

INTRODUCTION: Ticagrelor might reduce infarct size by exerting a more potent antiplatelet effect or by promoting a potential conditioning stimulus in ST-elevation myocardial infarction (STEMI) patients. Pre-infarction angina (PIA) is an effective preconditioning stimulus that reduces ischemia-reperfusion injury. Because little is known on the interaction of PIA in STEMI-patients loaded with ticagrelor, we sought to determine if patients loaded with ticagrelor had improved clinical outcomes as compared to clopidogrel and to study if it is modulated by the presence of PIA. METHODS: From 1272 STEMI patients submitted to primary percutaneous coronary intervention and treated with clopidogrel or ticagrelor from January 2008 to December 2018, 826 were analyzed after propensity score matching. Infarct size was estimated using peak creatine kinase (CK) and troponin T (TnT), and clinical impact was evaluated through cumulative major cardiac and cerebrovascular events (MACCE) at 1-year follow-up. Matched patients and their interaction with PIA were analyzed. RESULTS: Patients loaded with ticagrelor had lower peak CK [1405.50 U/L (730.25-2491.00), P < .001] and TnT [3.58 ng/mL (1.73-6.59), P < .001)], regardless of PIA. The presence of PIA was associated with lower CK (P = .030), but not TnT (P = .097). There was no interaction between ticagrelor loading and PIA (P = .788 for TnT and P = .555 for CK). There was no difference in MACCE incidence between clopidogrel or ticagrelor loading (P = .129). Cumulative survival was also similar between clopidogrel or ticagrelor, regardless of PIA (P = .103). CONCLUSION: Ticagrelor reduced infarct sizes independently and without a synergic effect with PIA. Despite reducing infarct size, clinical outcomes were similar across both groups.

Right Ventricular Septal Versus Apical Pacing: Long-Term Incidence of Heart Failure and Survival.

The clinical benefits of right ventricular septal (RVS) pacing compared to those of right ventricular apical (RVA) pacing are still in debate. We aimed to compare the incidence of heart failure (HF) and all-cause mortality in patients submitted to RVS and RVA pacing during a longer follow-up. This a single-center, retrospective study analysis of consecutive patients submitted to pacemaker implantation. The primary outcome was defined as the occurrence of HF during follow-up. The secondary outcome was all-cause death. A total of 251 patients were included, 47 (18.7%) with RVS pacing. RVS pacing was associated to younger age, male gender, lower body mass index, ischemic heart disease, and atrial fibrillation. During a follow-up period of 5.2 years, the primary outcome occurred in 89 (37.1%) patients. RVS pacing was independently associated with a 3-fold lower risk of HF, after adjustment. The secondary outcome occurred in 83 (34.2%) patients, and pacemaker lead position was not a predictor. Fluoroscopy time and rate of complications (rarely life-threatening) were similar in both groups. Our study points to a potential clinical benefit of RVS positioning, with a 3.3-fold lower risk of HF, without accompanying increase in procedure complexity nor complication rate.

Platypnoea Orthodeoxia Syndrome and Patent Foramen Ovale Closure: Single-Centre Experience and Long-Term Follow-Up.

INTRODUCTION: Platypnoea orthodeoxia syndrome (POS) is an uncommon condition characterised by dyspnoea and arterial desaturation induced by an upright position and relieved in the supine position, usually due to a patent foramen ovale (PFO). Percutaneous closure of a PFO is the preferred treatment to cure POS. This study aimed to evaluate the clinical and gasometrical characteristics and to describe the long-term outcomes of percutaneous PFO closure in a group of patients with POS. METHODS: Patients with POS and a PFO treated by percutaneous intervention from 2010-2020 were reviewed. The primary efficacy outcome was the arterial oxygen pressure to fraction of inspired oxygen (PaO2/FiO2) ratio before and 24 hours after the procedure. Total clinical success was considered if the arterial oxygen saturation measured by pulse oximetry (SpO2) improved to >94% in the supine and sitting positions without supplemental oxygen, while partial success was considered if SpO2 improved from baseline but still required oxygen to achieve >94%. Secondary outcomes were an absolute improvement in SpO2 and sense of dyspnoea, without significant residual shunt on transthoracic echocardiography (TTE) at follow-up. RESULTS: Of 168 patients undergoing PFO or atrial septal defect closure, 14 had POS (8.3%). Percutaneous PFO closure was successfully performed in all patients with a single device. Twelve of 14 patients had total clinical success (86%) and one patient had partial success. The PaO2/FiO2 ratio increased from 155.9±50.6 to 318.3±73.4 after PFO closure (p=0.002). All patients with total clinical success had a successful secondary efficacy outcome with an absolute improvement in SpO2 and complete resolution of dyspnoea, which was maintained at follow-up (37±20 months; range, 11 months to 6 years). None had a significant residual shunt between 12 and 24 months of follow-up. CONCLUSION: The PFO percutaneous closure was a successful, durable and safe method for patients presenting with POS; it achieved major improvements in both gasometrical parameters and quality of life.

Myocardial Bridging Leading to Cardiac Collapse in a Marathon Runner.

Myocardial bridging (MB) is a congenital coronary anomaly, which is defined as cardiac muscle overlying a portion of a coronary artery. Although traditionally considered benign in nature, increasing attention is being given to specific subsets of MB. Sports medicine recognizes MB as a cause of sudden death among young athletes. We present a case of a 30-year-old man who suddenly collapsed during a marathon running. Diagnostic workup with coronary computed tomography angiography revealed the presence of three simultaneous myocardial bridges in this patient, possibly explaining the exercise-induced syncope. The other diagnostic tests excluded seizures, cranioencephalic lesions, ionic or metabolic disturbances, acute coronary syndromes, cardiomyopathies, myocarditis, or conduction disturbances. Exertional syncope is a high-risk complaint in the marathon runner. In the context of intense physical activity, the increased sympathetic tone leading to tachycardia and increased myocardial contractility facilitates MB ischemia. In this illustrative case, the patient's syncope might probably be associated with an ischemia-induced arrhythmia secondary to MB and potentiated by dehydration in the context of prolonged stress (marathon running). In conclusion, this case highlights that MB may be associated with dangerous complications (myocardial ischemia and life-threatening ventricular arrhythmias), particularly during intense physical activity and in the presence of a long myocardial bridge.

Body Weight and Muscle Thickness Changes after Hemodialysis: A Pilot Study with Bayesian Approach.

Maintaining adequate body water balance is one aim of hemodialysis that is obtained by changing the blood volume. However, it is known that volume withdrawal is followed by water redistribution between extra- and intra-cellular spaces. In this context, the skeletal muscle tissue represents almost 50% of the total body mass, and like other soft tissues, consists of about 70%-80% water. Body weight is the main parameter used to monitor the body water change after a hemodialysis session, but it does not allow inferring about the water redistribution between extra and intracellular spaces. Thus, the present study aimed to assess the immediate impact of hemodialysis on body weight and the thickness of the rectus femoris muscle. Fifteen male patients with end-stage renal disease took part in the study. Muscle thickness, measured with ultrasound imaging, and body weight and were measured before (Pre) and after (Post) (within 5 to 10 minutes after) an hemodialysis session. Paired t-test was used to compare Pre and Post measures, and Bayesian analysis was applied to check the probability to replicate the same results (ie, the magnitude of the evidence). Our results indicated that body weight, but not rectus femoris muscle thickness, is significantly reduced immediately after hemodialysis. The rectus femoris muscle thickness seems not to be a reliable parameter to infer water redistribution after hemodialysis session.

The entropy of RR intervals is associated to gestational age in full-term newborns with adequate weight for gestational age.

INTRODUCTION: The variability of successive RR intervals has been pointed out as an indicator of systemic homeostasis. The entropy of successive RR intervals is associated with a greater adaptive capacity, which is essential after childbirth, characterized by a change from an intrauterine environment that constantly adapts to the fetal demands, to an extrauterine environment that requires constant biological adaptations by the neonate. OBJECTIVES: To analyze the association between gestational age (GA) and the entropy of RR intervals in term infants with adequate birth weight in the first hours of extrauterine life. METHODS: In a cross-sectional study design maternal, labor and neonatal characteristics were collected from the obstetric records. Successive RR intervals were recorded from neonates up to 72 hours (i.e. 3 days) of birth. SUBJECTS: Fifty term infants, healthy and with adequate birth weight. Outcome measures: the variability of RR intervals was analyzed obtaining the entropy of 1000 successive RR intervals. Pearson's correlation was used to evaluate the association between GA and the entropy of successive RR intervals, while linear regression was used to obtain the coefficient of determination (r2) as well as a prediction model. The adequacy of the prediction model was evaluated using the Komolgorov-Smirnov test to evaluate the residuals distribution. RESULTS: There was a positive and significant association between the studied variables (r = 0.437; p = .002). The coefficient of determination allowed us to infer that approximately 19.3% of the RR interval entropy from the studied sample can be explained by the GA (r2 = 0.193; p = .002). The analysis of the residuals distribution confirmed that the regression model obtained here was adequate. CONCLUSION: Our results indicate that, even within a normal range of GA (≥37 a < 42 weeks) and birth weight, a longer intrauterine life allows a greater entropy of successive RR intervals, indicating a greater maturation of biological systems and adaptive capacity.

Sympathetic activity is negatively associated to uremic state and hemodynamic instability during hemodialysis sessions / La actividad simpática está negativamente asociada al estado urémico y a la inestabilidad hemodinámica durante las sesiones de hemodiálisis

INTRODUCTION: Hemodynamic instabilities, characterized by oscillations of blood pressure, are common during hemodialysis sessions (HD), culminating in intradialytic hypotension owing to volume withdrawal from the cardiovascular system. The ability to carry out immediate adjusts in cardiovascular system, mainly mediated by the autonomic nervous system, is essential to the maintenance of hemodynamic stability during HD. OBJECTIVE: This study aimed to investigate the relationship between the sympathetic activity, and the hemodynamic stability from chronic kidney disease (CKD) patients during the HD, as well as the relationship between sympathetic activity and the uremic state. METHODS: Fourteen CKD patients (08 women and 06 men) with no history of recurrent ID episodes had the successive RR intervals recorded during HD. Blood pressure measurements were recorded at regular intervals of 30 minutes along 4 hours of each session. Hemodynamic stability was established by the standard deviation (SD), coefficient of variation (CV) and the Delta (difference between the highest and the lowest measure) of systolic (SBP), diastolic (DBP), and mean (MBP) blood pressures, as well as the pulse pressure (PP) from the 8 recordings obtained during each session. As a measure of autonomic heart control, the log-transformed low frequency (lnLFnu) spectral band was used. The uremic state was established by the mean of uremia from the last 12 months. Pearson's correlation was used to analyze the correlation between the studied variables. RESULTS: The lnLFnu values were negatively associated SD (SBP [r = -0.480; p = 0.010], PP [r = -0.504; p = 0.006] and MBP [r = -0.449; p = 0.017]), CV (SBP [r = -0.390; p = 0.040]) and delta (SBP [r = -0.438; p = 0.020], PP [r = -0.490; p = 0.008] and MBP [r = -0.382; p = 0.045]). lnLFnu was also negatively associated to the uremic state (r = -0.601; p = 0.01). CONCLUSIONS: Our results indicate that higher values of the lnLFnu are associated with better hemodynamic stability (i.e., smaller blood pressure oscillations) during HD sessions, in turn, the mean of blood urea concentration in the last 12 months, defined here as the uremic state, was associated with lower values of the lnLFnu during HD sessions

INTRODUCCIÓN: La inestabilidad hemodinámica, que se caracteriza por las oscilaciones de la presión arterial, es frecuente durante las sesiones de hemodiáilisis (HD) y tiene como resultado la hipotensión intradialítica, causada por una disminución en el volumen sanguíneo del sistema cardiovascular. Es esencial poder realizar ajustes inmediatos en el sistema cardiovascular, mediados principalmente por el sistema nervioso autónomo, a fin de mantener la estabilidad hemodinámica durante la hemodiálisis. OBJETIVO: El objetivo de nuestro estudio fue investigar la relación entre la actividad del sistema nervioso simpático y la estabilidad hemodinámica en pacientes con enfermedad renal crónica (ERC) durante las sesiones de hemoterapia; asimismo, se indagó sobre la relación entre la actividad del sistema nervioso simpático y el estado urémico. MATERIAL Y MÉTODOS: Se registraron, durante las sesiones de hemodiálisis, los intervalos RR sucesivos de 14 pacientes con enfermad renal crónica (8 mujeres y 6 hombres) sin antecedentes de episodios recurrentes de hipotensión intradialítica (HI). Se realizaron registros de la tensión arterial en intervalos regulares de 30 minutos durante 4 horas en cada sesión. La estabilidad hemodinámica se estableció mediante la desviación estándar, el coeficiente de variación (CV) y delta (diferencia entre la medida más alta y la más baja) de la tensión arterial sistólica (TAS), la diastólica (TAD) y la media (TAM), así como la tensión diferencial (TD) a partir de los ocho registros obtenidos durante cada sesión. Se utilizó el análisis espectral de transformaciones logarítmicas de baja frecuencia (LnLFnu, por su sigla en inglés) expresados en unidades normalizadas mediante transformación logarítmica. El estado urémico se determinó a través del promedio de los valores de uremia obtenidos durante los últimos doce meses. Se utilizó el coeficiente de correlación de Pearson para analizar las variables estudiadas. RESULTADOS: Mediante los distintos cálculos, se hallaron las siguientes correlaciones negativas con los valores de lnLFnu : SD (TAS [r = -0,480; p = 0,010]; TD [r = -0,504; p = 0,006] , y TAM [r = -0,449; p = 0,017]); CV (TAS [r = -0,390; p = 0,040]); y delta (TAS [r = -0,438; p = 0,020]; TD [r = -0,490; p = 0,008], y TAM [r = -0,382; p = 0,045]). También se observó una correlación negativa entre lnLFnu y el estado urémico (r = -0,601; p = 0,01). CONCLUSIONES: Nuestros resultados indican que los valores más elevados de LnLFnu se asocian con una mejor estabilidad hemodinámica, es decir, menor oscilación de la tensión arterial, durante las sesiones de hemodiálisis. A su vez, el promedio de concentración de urea en sangre registrado durante los últimos doce meses, al cual definimos como el estado urémico, se relacionó con valores más bajos de LnLFnu durante las sesiones de hemodiálisis

Exercise echocardiography and cardiac magnetic resonance imaging to predict outcome in patients with hypertrophic cardiomyopathy.

AIMS: We have observed that wall motion abnormalities (WMAs) during exercise echocardiography (ExE) are associated to events in hypertrophic cardiomyopathy (HCM). Our objective was to evaluate ExE and cardiac magnetic resonance (CMR) to predict outcome in HCM. METHODS AND RESULTS: ExE and CMR were performed in 148 patients with HCM. During follow-up (7.1 ± 2.7 years), there were 7 hard events (Hard-E) and 26 combined events (Comb-E). Exercise WMAs were observed in 13 patients (8.8%), perfusion defects in 10 (6.8%), and late gadolinium enhancement (LGE) in 48 (32.4%). WMAs were seen in 57% of patients with Hard-E vs. 6% without (P = 0.001) and in 23 and 6% with and without Comb-E (P = 0.005). Perfusion defects were also more frequent in patients with Hard-E than without (43 vs. 5%, P = 0.007) and in patients with Comb-E than without (23 vs. 5%, P = 0.002). LGE (g) was greater in patients with Comb-E than without [median (25th-75th percentile) 0 (0-21.1) vs. 0 (0-9.3) g P = 0.04]. Univariable predictors of Comb-E included NYHA class ≥2, peak double product, ΔWMSI, and CMR data. Peak double product [Hazard ratios (HR) = 0.99, confidence intervals (CI) 95% 0.99-0.99, P = 0.02] and ΔWMSI (HR = 404, CI 95% 12-13681, P = 0.001) remained independent predictors. Peak WMSI correlated with myocardial mass with LGE (r = 0.20, P = 0.02) and with perfusion defect area (r = 0.40, P < 0.001). LGE affecting ≥15% of the left ventricle was observed in 38% of patients with exercise WMAs vs. 12% without (P = 0.009). CONCLUSION: CMR data are associated to exercise WMAs in patients with HCM. ExE and CMR may help to predict outcome in them.

Multi-axial mechanical stimulation of tissue engineered cartilage: review.

The development of tissue engineered cartilage is a promising new approach for the repair of damaged or diseased tissue. Since it has proven difficult to generate cartilaginous tissue with properties similar to that of native articular cartilage, several studies have used mechanical stimuli as a means to improve the quantity and quality of the developed tissue. In this study, we have investigated the effect of multi-axial loading applied during in vitro tissue formation to better reflect the physiological forces that chondrocytes are subjected to in vivo. Dynamic combined compression-shear stimulation (5% compression and 5% shear strain amplitudes) increased both collagen and proteoglycan synthesis (76 +/- 8% and 73 +/- 5%, respectively) over the static (unstimulated) controls. When this multi-axial loading condition was applied to the chondrocyte cultures over a four week period, there were significant improvements in both extracellular matrix (ECM) accumulation and the mechanical properties of the in vitro-formed tissue (3-fold increase in compressive modulus and 1.75-fold increase in shear modulus). Stimulated tissues were also significantly thinner than the static controls (19% reduction) suggesting that there was a degree of ECM consolidation as a result of long-term multi-axial loading. This study demonstrated that stimulation by multi-axial forces can improve the quality of the in vitro-formed tissue, but additional studies are required to further optimize the conditions to favour improved biochemical and mechanical properties of the developed tissue.

Effect of sodium bicarbonate on extracellular pH, matrix accumulation, and morphology of cultured articular chondrocytes.

Tissue engineering is a promising approach for articular cartilage repair; however, attempts to develop tissue that mimic native cartilage have been problematic. The synthesis and accumulation of extracellular matrix macromolecules may be adversely affected by a change in pH of the media during cell culture. Typically, zwitterion buffers (e.g., HEPES) are used in culture media because they can perform under both slightly acidic and alkaline conditions. However, because chondrocytes tend to rapidly acidify the media, better pH maintenance may be achieved by utilizing additional buffering agents that operate under acidic conditions (e.g., bicarbonate). The purpose of this study was to investigate the combined effect of HEPES and sodium bicarbonate (NaHCO(3)) on extracellular pH and matrix accumulation by cultured articular chondrocytes. Isolated bovine articular chondrocytes were seeded on Millicell filters and cultured in HEPES-buffered media containing 0, 7, or 14 mM NaHCO(3). Throughout the 4-week culture period, the extracellular pH was more neutral with increasing NaHCO(3) concentration. Addition of NaHCO(3) increased synthesis (140 +/- 29%) and accumulation (20 +/- 2%) of proteoglycans whereas collagen was unaffected. There was also an increase in tissue cellularity (41 +/- 13%). Morphologically, increasing numbers of flattened cells, resembling superficial zone chondrocytes, localized to the surface of the in vitro-formed tissue with increasing NaHCO(3) supplementation were observed by light and transmission electron microscopy. Experiments are underway to determine whether these effects are due to pH maintenance or to the increased concentration of bicarbonate ions, which regulate intracellular pH.