The Caspase 1 Inhibitor VX-765 Protects the Isolated Rat Heart via the RISK Pathway.

PURPOSE: Protecting the heart from ischaemia-reperfusion (IR) injury is a major goal in patients presenting with an acute myocardial infarction. Pyroptosis is a novel form of cell death in which caspase 1 is activated and cleaves interleukin 1ß. VX-785 is a highly selective, prodrug caspase 1 inhibitor that is also clinically available. It has been shown to be protective against acute IR in vivo rat model, and therefore might be a promising possibility for future cardioprotective therapy. However, it is not known whether protection by VX-765 involves the reperfusion injury salvage kinase (RISK) pathway. We therefore investigated whether VX-765 protects the isolated, perfused rat heart via the PI3K/Akt pathway and whether protection was additive with ischaemic preconditioning (IPC). METHODS: Langendorff-perfused rat hearts were subject to ischaemia and reperfusion injury in the presence of 30 µM VX-765, with precedent IPC, or the combination of VX-765 and IPC. RESULTS: VX-765 reduced infarct size (28 vs 48% control; P < 0.05) to a similar extent as IPC (30%; P < 0.05). The PI3 kinase inhibitor, wortmannin, abolished the protective effect of VX-765. Importantly in the model used, we were unable to show additive protection with VX-765 + IPC. CONCLUSIONS: The caspase 1 inhibitor, VX-765, was able to reduce myocardial infarction in a model of IR injury. However, the addition of IPC did not demonstrate any further protection.

Rare presentation of an atrial myxoma in an adolescent patient: a case report and literature review.

BACKGROUND: Cardiac tumors are uncommon in the pediatric population. When present, cardiac manifestations stem from the tumor causing inflow or outflow obstruction. While common in adults, cardiac myxomas presenting with generalized systemic illness or peripheral emboli especially with no cardiac or neurological symptoms are rare in children. CASE PRESENTATION: We report a case of a previously healthy adolescent girl who presented with a 6-month history of constitutional symptoms and a purpuric rash with no cardiac or neurologic symptoms, found to have a cardiac myxoma. CONCLUSIONS: A vasculopathic rash in the setting of atrial myxomas has been shown be a precursor to significant morbidity and mortality. Due to the rarity of this entity, the time elapsed from onset of non-cardiac symptoms until diagnosis of a myxoma is usually prolonged with interval development of irreversible neurological sequelae and death reported in the literature. Therefore, we highlight the importance of including cardiac myxomas and paraneoplastic vasculitis early in the differential diagnosis for patients presenting with a purpuric rash and systemic symptoms.

Relationship between Static Lung Compliance and Extubation Failure in Postoperative Cardiac Surgery Patients. / Relação entre a Complacência Pulmonar Estática e a Falha de Extubação em Pacientes Pós-Operatório de Cirurgia Cardíaca.

BACKGROUND: Static lung compliance, which is seriously affected during surgery, can lead to respiratory failure and extubation failure, which is little explored in the decision to extubate after cardiac surgery. OBJECTIVE: To evaluate static lung compliance in the postoperative period of cardiac surgery and relate its possible reduction to cases of extubation failure in patients submitted to the fast-track method of extubation. METHODS: Patients undergoing cardiac surgery using cardiopulmonary bypass (CPB) at a state university hospital admitted to the ICU under sedation and residual block were included. Their static lung compliance was assessed on the mechanical ventilator using software that uses least squares fitting (LSF) for measurement. Within 48 hours of extubation, the patients were observed for the need for reintubation due to respiratory failure. The level of significance adopted for the statistical tests was 5%, i.e., p<0.05. RESULTS: 77 patients (75.49%) achieved successful extubation and 25 (24.51%) failed extubation. Patients who failed extubation had lower static lung compliance compared to those who succeeded (p<0.001). We identified the cut-off point for compliance through analysis of the Receiver Operating Characteristic Curve (ROC), with the cut-off point being compliance <41ml/cmH2O associated with a higher probability of extubation failure (p<0.001). In the multiple regression analysis, the influence of lung compliance (divided by the ROC curve cut-off point) was found to be 9.1 times greater for patients with compliance <41ml/cmH2O (p< 0.003). CONCLUSIONS: Static lung compliance <41ml/cmH2O is a factor that compromises the success of extubation in the postoperative period of cardiac surgery.

FUNDAMENTO: Pouco explorada na decisão de extubação no pós-operatório de cirurgia cardíaca, a complacência pulmonar estática seriamente afetada no procedimento cirúrgico pode levar à insuficiência respiratória e à falha na extubação. OBJETIVO: Avaliar a complacência pulmonar estática no pós-operatório de cirurgia cardíaca e relacionar sua possível redução aos casos de falha na extubação dos pacientes submetidos ao método fast-track de extubação. MÉTODOS: Foram incluídos pacientes que realizaram cirurgia cardíaca com uso de circulação extracorpórea (CEC) em um hospital universitário estadual admitidos na UTI sob sedação e bloqueio residual. Tiveram sua complacência pulmonar estática avaliada no ventilador mecânico por meio do software que utiliza o least squares fitting (LSF) para a medição. No período de 48 horas após a extubação os pacientes foram observados respeito à necessidade de reintubação por insuficiência respiratória. O nível de significância adotado para os testes estatísticos foi de 5%, ou seja, p<0,05. RESULTADOS: Obtiveram sucesso na extubação 77 pacientes (75,49%) e falharam 25 (24,51%). Os pacientes que falharam na extubação tiveram a complacência pulmonar estática mais baixa quando comparados aos que tiveram sucesso (p<0,001). Identificamos o ponto de corte para complacência por meio da análise da curva Receiver Operating Characteristic Curve (ROC) sendo o ponto de corte o valor da complacência <41ml/cmH2O associado com maior probabilidade de falha na extubação (p<0,001). Na análise de regressão múltipla, verificou-se a influência da complacência pulmonar (dividida pelo ponto de corte da curva ROC) com risco de falha 9,1 vezes maior para pacientes com complacência <41ml/cmH2O (p< 0,003). CONCLUSÕES: A complacência pulmonar estática <41ml/cmH2O é um fator que compromete o sucesso da extubação no pós-operatório de cirurgia cardíaca.

The influence of sex on left ventricular remodeling in patients with aortic dissection.

AIMS: Patients with aortic dissection have a high prevalence of left ventricular structural alterations, including left ventricular hypertrophy (LVH), but little is known about the impact of sex on this regard. This study compared clinical, cardiac, and prognostic characteristics between men and women with aortic dissection. METHODS: We retrospectively assessed clinical and echocardiographic characteristics, and 1-year mortality in 367 aortic dissection patients (30% women; 66% with Stanford-A) who underwent echocardiography 60 days before or after the diagnosis of aortic dissection from three Brazilian centers. RESULTS: Men and women had similar clinical characteristics, except for higher age (59.4 ±â€Š13.4 vs. 55.9 ±â€Š11.6 years; P = 0.013) and use of antihypertensive classes (1.4 ±â€Š1.3 vs. 1.1 ±â€Š1.2; P = 0.024) and diuretics (32 vs. 19%; P = 0.004) in women compared with men. Women had a higher prevalence of LVH (78 vs. 65%; P = 0.010) and lower prevalence of normal left ventricular geometry (20 vs. 10%; P = 0.015) than men. Logistic regression analysis adjusted for confounding factors showed that women were less likely to have normal left ventricular geometry (odds ratio, 95% confidence interval = 0.42, 0.20-0.87; P = 0.019) and were more likely to have LVH (odds ratio, 95% confidence interval = 1.91, 1.11-3.27; P = 0.019). Conversely, multivariable Cox-regression analysis showed that women had a similar risk of death compared to men 1 year after aortic dissection diagnosis (hazard ratio, 95% confidence interval = 1.16, 0.77-1.75; P = 0.49). CONCLUSION: In aortic dissection patients, women were typically older, had higher use of antihypertensive medications, and exhibited a greater prevalence of LVH compared with men. However, 1-year mortality after aortic dissection diagnosis did not differ between men and women.

Penetrating cardiac trauma: 20-y experience from a university teaching hospital.

BACKGROUND: Penetrating traumas, including gunshot and stab wounds, are the major causes of cardiac trauma. Our aim was to describe and compare the variables between patients with penetrating cardiac trauma in the past 20 y in a university hospital, identifying risk factors for morbidity and death. METHODS: Review of trauma registry data followed by descriptive statistical analysis comparing the periods 1990-1999 (group 1, 54 cases) and 2000-2009 (group 2, 39 cases). Clinical data at hospital admission, Injury Severity Score (ISS), Glasgow Coma Scale (GCS), and Revised Trauma Score (RTS) were recorded. RESULTS: The incidences of penetrating cardiac injuries were steady within the period of study in the chosen metropolitan area. The two groups were similar regarding age, mechanism of trauma (gunshot × stab), and ISS. Group 1 showed lower systolic blood pressure at admission (mean 87 versus 109 mm Hg), lower GCS (12.9 versus 14.1), lower RTS (6.4 versus 7.3), higher incidence of grade IV-V cardiac lesions (74% versus 48.7%), and were less likely to survive (0.83 versus 0.93). The major risk factor for death was gunshot wound (13 times higher than stab wound), systolic blood pressure < 90 mm Hg, GCS < 8, RTS < 7.84, associated injuries, grade IV-V injury, and ISS > 25. We observed a tendency in mortality reduction from 20.3% to 10.3% within the period of observation. CONCLUSIONS: Several associated factors for mortality and morbidity were identified. In the last decade, patients were admitted in better physiological condition, perhaps reflecting an improvement on prehospital treatment. We observed a trend toward a lower mortality rate.

Ventricular pacing threshold after transthoracic external defibrillation with two different waveforms: an experimental study.

AIMS: Although an increase in the ventricular pacing threshold (VPT) has been observed after administration of transthoracic shock for ventricular defibrillation, few studies have evaluated the phenomenon with respect to the defibrillation waveform energy. Therefore, this study examined the VPT behaviour after transthoracic shock with a monophasic or biphasic energy waveform. METHOD AND RESULTS: Domestic Landrace male piglets implanted with a permanent pacemaker stimulation system were divided into three groups: no ventricular fibrillation (VF) induction and transthoracic shock with monophasic or biphasic energy (group I); VF induction, 1 min of observation without intervention, 2 min of external cardiac massage, and transthoracic shock with monophasic or biphasic energy (group II); and VF induction, 2 min of observation without intervention, 4 min of external cardiac massage, and transthoracic shock with monophasic or biphasic energy (group III). After external shock, the VPT was evaluated every minute for 10 min. A total of 143 experiments were performed. At the end of the observation period, groups I and II showed steady VPT values. Group III showed an increase in VPT with monophasic or biphasic external energy, with no difference between the external energy sources. The monophasic but not the biphasic waveform was associated with higher VPT values when the VF was longer. CONCLUSION: Defibrillation does not have a significant impact on pacing threshold, but a longer VF period is related to a higher VPT after defibrillation with monophasic waveform.

Postoperative Period of Myocardial Revascularization Surgery: Retrospective Cohort Study of a Single Center.

INTRODUCTION: Risk factors and postoperative complications can worsen the condition of patients undergoing coronary artery bypass grafting; some of these factors and complications are closely related to mortality rate. OBJECTIVE: To describe clinical factors and outcomes related to mortality of patients undergoing coronary artery bypass grafting and on invasive mechanical ventilation. METHODS: This is a single-center retrospective data analysis of patients who underwent coronary artery bypass grafting on invasive mechanical ventilation between 2013 and 2019. Data regarding clinical characteristics, postoperative complications, intensive care unit and mechanical ventilation time, and their relationship with mortality were analyzed. RESULTS: Four hundred seventy-two patients who underwent coronary artery bypass grafting entered the study. Their mean age was 62.3 years, and mean body mass index was 27.3. The mortality rate was 4%. Fifty percent of the patients who had ventilator-associated pneumonia died. Considering the patients who underwent hemotherapy and hemodialysis, 20% and 33% died, respectively. Days of intensive care unit stay and high Acute Physiology and Chronic Health Evaluation score and Simplified Acute Physiology Score were significantly related to death. CONCLUSION: Factors and clinical conditions such as the patients' age, associated comorbidities, the occurrence of ventilator-associated pneumonia, length of stay in the intensive care unit, and mechanical ventilation time are related to higher mortality in patients undergoing coronary artery bypass grafting.

Determinants and prognostic value of in-hospital infection in patients waiting for permanent pacemaker implantation.

BACKGROUND: In-hospital delays in permanent cardiac pacemaker (PPM) implantation are common and may result in in-hospital infection among patients waiting for PPM implantation (pre-PPM-HI). This study investigated the predictors and prognostic impact of these events. METHODS: We retrospectively evaluated 905 consecutive patients (68.2 ± 16.0 years; 54% males) who underwent PPM implantation. Clinical characteristics, pre-PPM-HI and 30-day mortality were recorded and a risk score for pre-PPM-HI was generated using multivariable logistic regression coefficients. RESULTS: Eigthy-nine patients (10% of the sample) developed pre-PPM-HI. Multivariable logistic regression analysis identified urinary catheter use, complete atrioventricular block, implantation of temporary pacemaker and diabetes mellitus as independent predictors of pre-PPM-HI. The generated score (range 0-10.1) played a better role in predicting pre-PPM-HI than individual factors, yielding an area under the curve [95%CI] of 0.754 [0.705-0.803]. Patients with score ≥ 7.5 had 18-fold greater risk of developing pre-PPM-HI than those with score < 2.5. Furthermore, multivariable Cox-regression analysis showed that patients who developed pre-PPM-HI had greater 30-day mortality after PPM implantation (hazard ratio [95%CI] = 2.90 [1.18-7.16], p = 0.021) compared with their counterparts. CONCLUSIONS: This study reveals that pre-PPM-HI is an independent predictor of early mortality after PPM implantation. In addition, a clinical score developed from simple clinical variables accurately identified patients at high risk of pre-PPM-HI. In scenarios where delays in PPM implantation are unavoidable, such as reference hospitals with high demand, the use of this tool can potentially help in the hierarchy of patients and in the reduction of this adverse event.

Pulmonary Hypertension in Obese Mice Is Accompanied by a Reduction in PPAR-γ Expression in Pulmonary Artery.

Obesity and insulin resistance (IR) are well-studied risk factors for systemic cardiovascular disease, but their impact on pulmonary hypertension (PH) is not well clarified. This study aims to investigate if diet-induced obesity induces PH and if peroxisome-proliferator-activated receptor (PPAR-γ) and/or endoplasmic reticulum (ER) stress are involved in this process. Mice were maintained on a high-fat diet (HFD) for 4 months, and IR and PH were confirmed. In a separate group, after 4 months of HFD, mice were treated with pioglitazone (PIO) or 4-phenylbutyric acid for the last month. The results demonstrated that HFD for at least 4 months is able to increase pulmonary artery pressure, which is maintained, and this animal model can be used to investigate the link between IR and PH, without changes in ER stress in the pulmonary artery. There was also a reduction in circulating adiponectin and in perivascular adiponectin expression in the pulmonary artery, associated with a reduction in PPAR-γ expression. Treatment with PIO improved IR and PH and reversed the lower expression of adiponectin and PPAR-γ in the pulmonary artery, highlighting this drug as potential benefit for this poorly recognized complication of obesity.

Impact of Hypertension History and Blood Pressure at Presentation on Cardiac Remodeling and Mortality in Aortic Dissection.

OBJECTIVE: This study compared clinical, echocardiographic, and prognostic characteristics among patients with aortic dissection (AD) with (HypHist) and without (No-HypHist) hypertension history and evaluated the association of blood pressure (BP) at presentation with 1-year mortality, left ventricular (LV) remodeling and renal dysfunction. METHODS: We investigated clinical and echocardiographic characteristics and 1-year mortality among 367 patients with AD (81% HypHist, 66% Type-A) from three Brazilian centers. RESULTS: Patients with No-HypHist were more likely to have Marfan syndrome, bicuspid aortic valve, to undergo surgical therapy, were less likely to have LV hypertrophy and concentricity, and had similar mortality compared with HypHist patients. Adjusted restricted cubic spline analysis showed that systolic BP (SBP) and diastolic BP (DBP) at presentation had a J-curve association with mortality among patients with No-HypHist, but did not associate with death among patients with HypHist (p for interaction = 0.001 for SBP and = 0.022 for DBP). Conversely, the association between SBP at presentation and mortality was influenced by previous use of antihypertensive medications in the HypHist group (p for interaction = 0.002). Results of multivariable logistic regression analysis comprising the whole sample showed direct associations of SBP and DBP at presentation with LV hypertrophy (p = 0.009) and LV concentricity (p = 0.015), respectively, and an inverse association between pulse pressure at presentation and estimated glomerular filtration rate (eGFR) <60 ml/min/1.73 m2 (p = 0.008). CONCLUSION: Combined information on BP at presentation, previous diagnosis of hypertension, and use of antihypertensive medications might be useful to predict mortality risk and to estimate extra-aortic end-organ damage among patients with AD.

Left Ventricular Concentric Geometric Patterns Are Associated With Worse Prognosis Among Patients With Type-A Aortic Dissection.

Background This study compared left ventricular (LV) characteristics between patients with type-A and type-B aortic dissection (AD) and evaluated the ability of LV remodeling phenotypes (hypertrophy, concentricity, or geometric patterns) to predict mortality in both AD types. Methods and Results We evaluated 236 patients with type A and 120 patients with type B who had echocardiograms within 60 days before or after AD diagnosis (median [25th, 75th percentiles] time difference between echocardiogram and AD diagnosis=1 [0, 6] days) from 3 centers. Patients were stratified according to LV phenotypes, and early (90-day) and late (1-year) mortality after AD diagnosis were assessed. In adjusted logistic regression analysis, patients with type A had higher and lower odds of concentric and eccentric hypertrophy (odds ratio [OR], 2.56; 95% CI, 1.50-4.36; P<0.001; and OR, 0.55; 95% CI, 0.31-0.97; P=0.039, respectively) than those with type B. Results of multivariable Cox-regression analysis showed that LV remodeling phenotypes were not related to mortality in patients with type B. By contrast, LV concentricity was associated with greater early and late mortality (hazard ratio [HR], 2.22; 95% CI, 1.24-3.96; P=0.007 and HR, 2.06; 95% CI, 1.20-3.54; P=0.009, respectively) in type A. In further analysis considering normal LV geometry as reference, LV concentric remodeling and concentric hypertrophy were associated with early mortality (HR, 7.78; 95% CI, 2.35-25.78; P<0.001 and HR, 4.38; 95% CI, 1.47-13.11; P=0.008, respectively), whereas concentric remodeling was associated with late mortality (HR, 5.40; 95% CI, 1.91-15.26; P<0.001) among patients with type A. Assessment of LV geometric patterns and concentricity provided incremental prognostic value in predicting early and late mortality beyond clinical variables in patients with type A based on net reclassification improvement and integrated discrimination improvement. Conclusions LV geometric patterns derived from LV concentricity were associated with greater mortality among patients with type A and may be markers of adverse prognosis in this population.

Relação entre a Complacência Pulmonar Estática e a Falha de Extubação em Pacientes Pós-Operatório de Cirurgia Cardíaca / Relationship between Static Lung Compliance and Extubation Failure in Postoperative Cardiac Surgery Patients

Resumo Fundamento: Pouco explorada na decisão de extubação no pós-operatório de cirurgia cardíaca, a complacência pulmonar estática seriamente afetada no procedimento cirúrgico pode levar à insuficiência respiratória e à falha na extubação. Objetivo: Avaliar a complacência pulmonar estática no pós-operatório de cirurgia cardíaca e relacionar sua possível redução aos casos de falha na extubação dos pacientes submetidos ao método fast-track de extubação. Métodos: Foram incluídos pacientes que realizaram cirurgia cardíaca com uso de circulação extracorpórea (CEC) em um hospital universitário estadual admitidos na UTI sob sedação e bloqueio residual. Tiveram sua complacência pulmonar estática avaliada no ventilador mecânico por meio do software que utiliza o least squares fitting (LSF) para a medição. No período de 48 horas após a extubação os pacientes foram observados respeito à necessidade de reintubação por insuficiência respiratória. O nível de significância adotado para os testes estatísticos foi de 5%, ou seja, p<0,05. Resultados: Obtiveram sucesso na extubação 77 pacientes (75,49%) e falharam 25 (24,51%). Os pacientes que falharam na extubação tiveram a complacência pulmonar estática mais baixa quando comparados aos que tiveram sucesso (p<0,001). Identificamos o ponto de corte para complacência por meio da análise da curva Receiver Operating Characteristic Curve (ROC) sendo o ponto de corte o valor da complacência <41ml/cmH2O associado com maior probabilidade de falha na extubação (p<0,001). Na análise de regressão múltipla, verificou-se a influência da complacência pulmonar (dividida pelo ponto de corte da curva ROC) com risco de falha 9,1 vezes maior para pacientes com complacência <41ml/cmH2O (p< 0,003). Conclusões: A complacência pulmonar estática <41ml/cmH2O é um fator que compromete o sucesso da extubação no pós-operatório de cirurgia cardíaca.

Abstract Background: Static lung compliance, which is seriously affected during surgery, can lead to respiratory failure and extubation failure, which is little explored in the decision to extubate after cardiac surgery. Objective: To evaluate static lung compliance in the postoperative period of cardiac surgery and relate its possible reduction to cases of extubation failure in patients submitted to the fast-track method of extubation. Methods: Patients undergoing cardiac surgery using cardiopulmonary bypass (CPB) at a state university hospital admitted to the ICU under sedation and residual block were included. Their static lung compliance was assessed on the mechanical ventilator using software that uses least squares fitting (LSF) for measurement. Within 48 hours of extubation, the patients were observed for the need for reintubation due to respiratory failure. The level of significance adopted for the statistical tests was 5%, i.e., p<0.05. Results: 77 patients (75.49%) achieved successful extubation and 25 (24.51%) failed extubation. Patients who failed extubation had lower static lung compliance compared to those who succeeded (p<0.001). We identified the cut-off point for compliance through analysis of the Receiver Operating Characteristic Curve (ROC), with the cut-off point being compliance <41ml/cmH2O associated with a higher probability of extubation failure (p<0.001). In the multiple regression analysis, the influence of lung compliance (divided by the ROC curve cut-off point) was found to be 9.1 times greater for patients with compliance <41ml/cmH2O (p< 0.003). Conclusions: Static lung compliance <41ml/cmH2O is a factor that compromises the success of extubation in the postoperative period of cardiac surgery.

Lidocaine and Pinacidil Added to Blood versus Crystalloid Cardioplegic Solutions: Study in Isolated Hearts.

OBJECTIVE: The present study aimed the functional recovery evaluation after long term of cardiac arrest induced by Custodiol (crystalloid-based) versus del Nido (blood-based) solutions, both added lidocaine and pinacidil as cardioplegic agents. Experiments were performed in isolated rat heart perfusion models. METHODS: Male rat heart perfusions, according to Langendorff technique, were induced to cause 3 hours of cardiac arrest with a single dose. The hearts were assigned to one of the following three groups: (I) control; (II) Custodiol-LP; and (III) del Nido-LP. They were evaluated after ischemia throughout 90 minutes of reperfusion. Left ventricular contractility function was reported as percentage of recovery, expressed by developed pressure, maximum dP/dt, minimum dP/dt, and rate pressure product variables. In addition, coronary resistance and myocardial injury marker by alpha-fodrin degradation were also evaluated. RESULTS: At 90 minutes of reperfusion, both solutions had superior left ventricular contractile recovery function than the control group. Del Nido-LP was superior to Custodiol-LP in maximum dP/dt (46%±8 vs. 67%±7, P<0.05) and minimum dP/dt (31%±4 vs. 51%±9, P<0.05) variables. Coronary resistance was lower in del Nido-LP group than in Custodiol-LP (395%±50 vs. 307%±13, P<0.05), as well as alpha-fodrin degradation, with lower levels in del Nido-LP group (P<0.05). CONCLUSION: Del Nido-LP cardioplegia showed higher functional recovery after 3 hours of ischemia. The analysis of alpha-fodrin degradation showed del Nido-LP solution provided greater protection against myocardial ischemia and reperfusion (IR) in this experimental model.

P-wave duration is a predictor for long-term mortality in post-CABG patients.

Risk stratification in secondary prevention has emerged as an unmet clinical need in order to mitigate the Number-Needed-to-Treat and make expensive therapies both clinically relevant and cost-effective. P wave indices reflect atrial conduction, which is a sensitive marker for inflammatory, metabolic, and pressure overload myocardial cell remodeling; the three stimuli are traditional mechanisms for adverse clinical evolution. Accordingly, we sought to investigate the predictive role of P-wave indices to estimate residual risk in patients with chronic coronary artery disease (CAD). The cohort included 520 post-Coronary Artery Bypass Grafting patients with a median age of 60 years who were followed for a median period of 1025 days. The primary endpoint was long-term all-cause death. Cubic spline model demonstrated a linear association between P-wave duration and incidence rate of long-term all-cause death (p = 0.023). P-wave >110ms was a marker for an average of 425 days shorter survival as compared with P-wave under 80ms (Logrank p = 0.020). The Cox stepwise regression models retained P-wave duration as independent marker (HR:1.37; 95%CI:1.05-1.79,p = 0.023). In conclusion, the present study suggests that P-wave measurement may constitute a simple, inexpensive and accessible prognostic tool to be added in the bedside risk estimation in CAD patients.

Myocardial tissue remodeling after orthotopic heart transplantation: a pilot cardiac magnetic resonance study.

After orthotopic heart transplantation (OHT), the allograft undergoes characteristic alterations in myocardial structure, including hypertrophy, increased ventricular stiffness, ischemia, and inflammation, all of which may decrease overall graft survival. Methods to quantify these phenotypes may clarify the pathophysiology of progressive graft dysfunction post-OHT. We performed cardiac magnetic resonance (CMR) with T1 mapping in 26 OHT recipients (mean age 47 ± 7 years, 30 % female, median follow-up post-OHT 6 months) and 30 age-matched healthy volunteers (mean age 50.5 ± 15 years; LVEF 63.5 ± 7 %). OHT recipients had a normal left ventricular ejection fraction (LVEF 65.3 ± 11 %) with higher LV mass relative to age-matched healthy volunteers (114 ± 27 vs. 85.8 ± 18 g; p < 0.001). There was no late gadolinium enhancement in either group. Both myocardial extracellular volume fraction (ECV) and intracellular lifetime of water (τic), a measure of cardiomyocyte hypertrophy, were higher in patients post-OHT (ECV: 0.39 ± 0.06 vs. 0.28 ± 0.03, p < 0.0001; τic: 0.12 ± 0.08 vs. 0.08 ± 0.03, p < 0.001). ECV was associated with LV mass (r = 0.74, p < 0.001). In follow-up, OHT recipients with normal biopsies by pathology (ISHLT grade 0R) in the first year post-OHT exhibited a lower ECV relative to patients with any rejection ≥2R (0.35 ± 0.02 for 0R vs. 0.45 ± 0, p < 0.001). Higher ECV but not LVEF was significantly associated with a reduced rejection-free survival. After OHT, markers of tissue remodeling by CMR (ECV and τic) are elevated and associated with myocardial hypertrophy. Interstitial myocardial remodeling (by ECV) is associated with cellular rejection. Further research on the impact of graft preservation and early immunosuppression on tissue-level remodeling of the allograft is necessary to delineate the clinical implications of these findings.

A Novel Surgical Approach to Mechanical Circulatory Support in Univentricular Infants.

BACKGROUND: Historically, the options for mechanical circulatory support in infants, particularly those with single-ventricle physiology, have been limited and outcomes have generally been poor. We report a new approach implemented for long-term support in a series of such patients. METHODS: This study is a single-center case series of 7 patients with single-ventricle physiology after stage 1 palliation supported with mechanical circulatory support using a novel technique, between May 2014 and September 2015. Our technique included modification and implantation of commercially available pediatric cannulae into the common atrium and the ascending aorta or reconstructed neoaorta and utilization of a centrifugal extracorporeal pump. RESULTS: Median circulatory support duration was 64 days (range, 35 to 99). One adverse neurologic event was observed in 1 patient, and bleeding requiring reoperation in 2 patients. Support to recovery, decision, or heart transplantation was accomplished in all cases. Of all patients, 43% were successfully discharged home. CONCLUSIONS: Our experience shows that long-term extracorporeal mechanical circulatory support of patients with underlying single-ventricle physiology after stage 1 palliation is feasible utilizing our technique. This approach overcomes several major challenges encountered in these patients, such as high flow requirement and stability of the cannulae, and allows extubation, rehabilitation, and at times, myocardial recovery.

Correction: Atorvastatin Improves Ventricular Remodeling after Myocardial Infarction by Interfering with Collagen Metabolism.

[This corrects the article DOI: 10.1371/journal.pone.0166845.].

Atorvastatin Improves Ventricular Remodeling after Myocardial Infarction by Interfering with Collagen Metabolism.

PURPOSE: Therapeutic strategies that modulate ventricular remodeling can be useful after acute myocardial infarction (MI). In particular, statins may exert effects on molecular pathways involved in collagen metabolism. The aim of this study was to determine whether treatment with atorvastatin for 4 weeks would lead to changes in collagen metabolism and ventricular remodeling in a rat model of MI. METHODS: Male Wistar rats were used in this study. MI was induced in rats by ligation of the left anterior descending coronary artery (LAD). Animals were randomized into three groups, according to treatment: sham surgery without LAD ligation (sham group, n = 14), LAD ligation followed by 10mg atorvastatin/kg/day for 4 weeks (atorvastatin group, n = 24), or LAD ligation followed by saline solution for 4 weeks (control group, n = 27). After 4 weeks, hemodynamic characteristics were obtained by a pressure-volume catheter. Hearts were removed, and the left ventricles were subjected to histologic analysis of the extents of fibrosis and collagen deposition, as well as the myocyte cross-sectional area. Expression levels of mediators involved in collagen metabolism and inflammation were also assessed. RESULTS: End-diastolic volume, fibrotic content, and myocyte cross-sectional area were significantly reduced in the atorvastatin compared to the control group. Atorvastatin modulated expression levels of proteins related to collagen metabolism, including MMP1, TIMP1, COL I, PCPE, and SPARC, in remote infarct regions. Atorvastatin had anti-inflammatory effects, as indicated by lower expression levels of TLR4, IL-1, and NF-kB p50. CONCLUSION: Treatment with atorvastatin for 4 weeks was able to attenuate ventricular dysfunction, fibrosis, and left ventricular hypertrophy after MI in rats, perhaps in part through effects on collagen metabolism and inflammation. Atorvastatin may be useful for limiting ventricular remodeling after myocardial ischemic events.

Diacerein improves left ventricular remodeling and cardiac function by reducing the inflammatory response after myocardial infarction.

BACKGROUND: The inflammatory response has been implicated in the pathogenesis of left ventricular (LV) remodeling after myocardial infarction (MI). An anthraquinone compound with anti-inflammatory properties, diacerein inhibits the synthesis and activity of pro-inflammatory cytokines, such as tumor necrosis factor and interleukins 1 and 6. The purpose of this study was to investigate the effects of diacerein on ventricular remodeling in vivo. METHODS AND RESULTS: Ligation of the left anterior descending artery was used to induce MI in an experimental rat model. Rats were divided into two groups: a control group that received saline solution (n = 16) and a group that received diacerein (80 mg/kg) daily (n = 10). After 4 weeks, the LV volume, cellular signaling, caspase 3 activity, and nuclear factor kappa B (NF-κB) transcription were compared between the two groups. After 4 weeks, end-diastolic and end-systolic LV volumes were reduced in the treatment group compared to the control group (p < .01 and p < .01, respectively). Compared to control rats, diacerein-treated rats exhibited less fibrosis in the LV (14.65%± 7.27% vs. 22.57%± 8.94%; p < .01), lower levels of caspase-3 activity, and lower levels of NF-κB p65 transcription. CONCLUSIONS: Treatment with diacerein once a day for 4 weeks after MI improved ventricular remodeling by promoting lower end-systolic and end-diastolic LV volumes. Diacerein also reduced fibrosis in the LV. These effects might be associated with partial blockage of the NF-κB pathway.