Abstract Background Focal intimal disruption (FID) has been described in >20% of type B intramural hematomas (IMH), with unclear prognosis and management. Objectives This study aimed to evaluate the ...short- and long-term evolution of medically treated patients with type B IMH with and without FID. Methods There were 107 consecutive patients with acute type B IMH were included prospectively in a multicenter protocol of clinical and imaging follow-up. FID was defined as an intimal disruption with contrast material-filled outpouching from the aorta lumen with a communicating orifice of >3 mm. Results There were 43 patients (40%) who developed an FID with larger basal maximum aortic diameter and hematoma thickness. Patients with acute FID had a higher risk of aorta-related events than those without FID (hazard ratio: 24.43; 95% confidence interval: 7.65 to 78.04; p < 0.001). Of the 94 discharged patients, 33 (35%) developed an FID within the first 6 months of follow-up: 19 evolved with mild (<1 mm/year), 8 with moderate (1 to 2 mm/year), and 6 with severe (>2 mm/year) aortic enlargement. Chronic FID was not associated with aorta-related events (hazard ratio: 0.98; 95% confidence interval: 0.22 to 4.34; p = 0.987). Conclusions The development of FID in the acute phase of type B IMH has a poor prognosis owing to the high risk of aortic rupture. In the chronic phase, most FIDs evolve with slow aortic dilation and without complications. Although acute FIDs should be treated early and invasively, lesions developing in the subacute-chronic phase can be managed with medical treatment and close imaging surveillance.
Aged cardiomyocytes develop a mismatch between energy demand and supply, the severity of which determines the onset of heart failure, and become prone to undergo cell death. The FoF1‐ATP synthase is ...the molecular machine that provides >90% of the ATP consumed by healthy cardiomyocytes and is proposed to form the mitochondrial permeability transition pore (mPTP), an energy‐dissipating channel involved in cell death. We investigated whether aging alters FoF1‐ATP synthase self‐assembly, a fundamental biological process involved in mitochondrial cristae morphology and energy efficiency, and the functional consequences this may have. Purified heart mitochondria and cardiomyocytes from aging mice displayed an impaired dimerization of FoF1‐ATP synthase (blue native and proximity ligation assay), associated with abnormal mitochondrial cristae tip curvature (TEM). Defective dimerization did not modify the in vitro hydrolase activity of FoF1‐ATP synthase but reduced the efficiency of oxidative phosphorylation in intact mitochondria (in which membrane architecture plays a fundamental role) and increased cardiomyocytes’ susceptibility to undergo energy collapse by mPTP. High throughput proteomics and fluorescence immunolabeling identified glycation of 5 subunits of FoF1‐ATP synthase as the causative mechanism of the altered dimerization. In vitro induction of FoF1‐ATP synthase glycation in H9c2 myoblasts recapitulated the age‐related defective FoF1‐ATP synthase assembly, reduced the relative contribution of oxidative phosphorylation to cell energy metabolism, and increased mPTP susceptibility. These results identify altered dimerization of FoF1‐ATP synthase secondary to enzyme glycation as a novel pathophysiological mechanism involved in mitochondrial cristae remodeling, energy deficiency, and increased vulnerability of cardiomyocytes to undergo mitochondrial failure during aging.
This study identified FoF1‐ATP synthase as a prominent target of dicarbonyl stress in cardiomyocytes during aging. Non‐enzymatic glycation of several units within FoF1‐ATP synthase holocomplex is proposed to interfere with spontaneous enzyme dimerization/oligomerization, which in turn reduces cristae curvature and energy efficiency in intact mitochondria and increases the sensitivity of cardiomyocytes to undergo pathological mitochondrial permeabilization in response to stress.
Background
Chronic total occlusions (CTOs) are present in more than one third of older patients with myocardial ischemia, but controversy remains about the best therapeutic approach.
Aims
To compare ...long‐term survival after CTO revascularization (percutaneous coronary intervention PCI or coronary artery bypass graft CABG) versus medical treatment (MT) alone in patients aged 75 and older.
Methods and results
A total of 1,252 consecutive patients with at least one CTO were identified from 2010 to 2014 in our center. Patients were stratified by age (<75 years vs. ≥75 years) in the present analysis. All‐cause and cardiac mortality were assessed at a median follow‐up of 3.5 years.
In the older subgroup (26%), patients were more likely to be treated with MT alone (71% vs. 43% of younger patients; p < 0.001). Patients undergoing revascularization were younger and had higher left ventricular ejection fraction (LVEF) and lower age, creatinine, ejection fraction (ACEF) score (age/LVEF +1 if creatinine >2.0 mg/dL), compared to the MT group (p < 0.05). As compared to MT, revascularization predicted lower rates of cardiac mortality and all‐cause mortality in older patients, both in the subgroups treated with CABG (hazard ratio HR 0.35, 95% confidence interval CI 0.17–0.71; HR 0.39, 95%CI 0.18–0.81) and PCI (HR 0.57, 95%CI 0.33–0.98; HR 0.59, 95%CI 0.28–1.2). No differences in mortality were observed according to type of revascularization procedure.
Conclusions
Among patients aged at least 75 years with a CTO, revascularization (PCI or CABG) rather than MT alone may portend a better outcome in terms of all‐cause and cardiac mortality.
Este trabajo tiene como objetivo, conocer las condiciones de vida de los trabajadores/as en plataformas en línea, basada en la ubicación para el traslado de personas y productos. Es una investigación ...exploratoria, de tipo cualitativa, se tuvo acceso a la población a conveniencia. El instrumento fue un cuestionario semi estructurado y la técnica la entrevista. En ellas se pudo conocer las condiciones de precariedad laboral, al ser trabajadores por cuenta propia. Las aplicaciones establecen ciertos acuerdos implícitos en la contratación, para las diversas modalidades de trabajo, remuneración e incentivos, no así riesgos laborales los cuales van por cuenta propia de los trabajadores. Los motivos para incursionar en esta actividad se dieron por necesidad de contar con mayor ingreso económico en la familia, como un adicional a los trabajos estables y otros por necesidad de contar con algún ingreso debido a que quedaron sin trabajo. La gran mayoría de los entrevistados manifiesta que esta actividad es temporal y no un trabajo permanente.
•The achievement of target doses in heart failure (HF) with reduced ejection fraction is feasible in most patients.•50% of patients achieve left ventricular reverse remodeling after HF therapy ...optimization.•50% of patients lose the potential implantable cardioverter defibrillator (ICD) indication after HF therapy optimization.•The proposed risk score may help to decide the timing of ICD implantation.•The use of a wearable-ICD may prevent mortality during HF therapy optimization.
A prophylactic implantable cardioverter defibrillator (ICD) in patients with heart failure and reduced left ventricular ejection fraction (HFrEF) is only indicated when left ventricular ejection fraction (LVEF) reassessment remains ≤35% after 3–6 months on optimal pharmacological therapy. However, LVEF may not improve during this period and the patient may be exposed to an unnecessary risk of sudden cardiac death. This study aimed to determine the incidence and predictors of the absence of left ventricular reverse remodeling (LVRR) after pharmacological treatment optimization in patients with HFrEF to design a risk score of absence of LVRR.
Consecutive outpatients with LVEF ≤35% were included in this observational prospective study. Up-titration of angiotensin-converting enzyme (ACE) inhibitors/angiotensin II receptor blockers (ARBs), beta-blockers, mineralocorticoid receptor antagonists (MRAs), and ivabradine was performed in our Heart Failure (HF) Unit. The absence of LVRR was defined as the persistence of an LVEF ≤35% at the 6-month follow-up.
One hundred and twenty patients were included. At the 6-month follow-up, 64%, 76%, 72%, and 7% of patients were at 100% of the target dose of ACE inhibitors/ARBs, beta-blockers, MRAs, and ivabradine, respectively. LVRR was observed in 48% of the patients. Ischemic cardiomyopathy, prolonged HF duration, and larger left ventricular end-diastolic diameter index (LVEDDI) were independent predictors of the absence of LVRR. The risk score based on these predictors showed a c-statistic value of 0.81.
Pharmacological treatment optimization is associated with LVRR in approximately half of cases, reducing potential ICD indications in parallel. However, ischemic cardiomyopathy, prolonged HF duration, and larger LVEDDI predict the absence of LVRR and favor ICD implantation without delay. The risk score based on the former predictors may help the clinician with the timing of ICD implantation.
To assess different warranty periods following a normal myocardial perfusion SPECT based on patients’ clinical characteristics and the type of stress performed.
A study was done of 2,922 consecutive ...patients (62.9 ± 13 years; 53.4% women) with a normal stress-rest SPECT. The warranty period was defined as the period during which patients remained at a low risk (<1% events/year) of total mortality (TM), or hard events (HE) (cardiac death or non-fatal myocardial infarction). Of these patients, 2,051 were given an exercise myocardial perfusion imaging (Ex-MPI); 461 submaximal exercise plus dipyridamole (Ex+Dipy-MPI); and 410 dipyridamole (Dipy-MPI). During a mean follow-up of 5 ± 3.3 years, a significant reduction (P < .05) of the warranty period for TM (13.5, 9.6 and 8 months) and HE (34.8, 20.5 and 8.2 months) was observed, for Ex-MPI, Ex+Dipy-MPI and Dipy-MPI, respectively. Other warranty period determinants were the clinical variables of age, sex, diabetes and known coronary artery disease. An abnormal left ventricular ejection fraction on gated-SPECT also significantly shortened the warranty period for HE in patients undergoing Ex+Dipy-MPI (P = .001) or Dipy-MPI alone (P = .007).
The warranty period for a normal stress-rest SPECT is highly variable since it is primarily determined by the type of stress, the patient’s clinical characteristics and LVEF.
Randomized clinical trials that enroll patients in critical or emergency care (acute care) setting are challenging because of narrow time windows for recruitment and the inability of many patients to ...provide informed consent. To assess the extent that recruitment challenges lead to randomized clinical trial discontinuation, we compared the discontinuation of acute care and nonacute care randomized clinical trials.
Retrospective cohort of 894 randomized clinical trials approved by six institutional review boards in Switzerland, Germany, and Canada between 2000 and 2003.
Randomized clinical trials involving patients in an acute or nonacute care setting.
We recorded trial characteristics, self-reported trial discontinuation, and self-reported reasons for discontinuation from protocols, corresponding publications, institutional review board files, and a survey of investigators.
Of 894 randomized clinical trials, 64 (7%) were acute care randomized clinical trials (29 critical care and 35 emergency care). Compared with the 830 nonacute care randomized clinical trials, acute care randomized clinical trials were more frequently discontinued (28 of 64, 44% vs 221 of 830, 27%; p = 0.004). Slow recruitment was the most frequent reason for discontinuation, both in acute care (13 of 64, 20%) and in nonacute care randomized clinical trials (7 of 64, 11%). Logistic regression analyses suggested the acute care setting as an independent risk factor for randomized clinical trial discontinuation specifically as a result of slow recruitment (odds ratio, 4.00; 95% CI, 1.72-9.31) after adjusting for other established risk factors, including nonindustry sponsorship and small sample size.
Acute care randomized clinical trials are more vulnerable to premature discontinuation than nonacute care randomized clinical trials and have an approximately four-fold higher risk of discontinuation due to slow recruitment. These results highlight the need for strategies to reliably prevent and resolve slow patient recruitment in randomized clinical trials conducted in the critical and emergency care setting.
Background
Chronic total occlusion (CTO) is common in patients with diabetes mellitus. Data on the long‐term outcomes after treatment of CTOs in this high‐risk population are scarce.
Aim
To compare ...the long‐term clinical outcomes of CTO revascularization either by coronary artery bypass graft (CABG) or successful percutaneous coronary intervention (PCI) versus optimal medical treatment (MT) alone in patients with diabetes.
Methods and Results
A total of 538 consecutive patients with diabetes and at least one CTO were identified from 2010 to 2014 in our center. In the present analysis, patients were stratified according to the CTO treatment strategy that was selected. MT was selected in 61% of patients whereas revascularization in the remaining 39%. Patients undergoing revascularization were younger, had higher left ventricular ejection fraction (LVEF), lower ACEF score, and more positive myocardial ischemia detection results compared to the MT group (p < .001).Patients referred for CABG had higher rates of left main disease compared to the PCI and MT groups (32% vs. 3% and 11%, respectively; p < .001). Complete revascularization was more often achieved in the CABG group, compared to the PCI group (62% vs. 32% p < .001). Multivariable analysis showed that revascularization with CABG was associated with lower rates of all‐cause and cardiac mortality rates compared to MT, hazard ratio (HR) 0.41, 95% confidence interval (CI) 0.25–0.70, p < .001 and HR 0.40, 95% CI 0.20–81, p = .011, respectively. Successful CTO‐PCI showed a trend towards benefit in all‐cause mortality (HR 0.58, 95% CI 0.33–1.04, p = .06).
Conclusion
In our registry, CTO revascularization in diabetic patients, especially with CABG, was associated with lower long‐term mortality rates as compared to MT alone.
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