Racial and ethnic differences in patients enrolled in the national bronchiectasis and nontuberculous mycobacteria research registry.

Demographic and socioeconomic factors are recognized to contribute to disparities in healthcare outcomes. Originally, bronchiectasis was described in a population of predominantly White ethnic group of patients in which racial disparity could not be identified. The U.S. Bronchiectasis Research Registry (BRR), a centralized database of adult patients with bronchiectasis and/or NTM from 18 clinical institutions across the U.S., was created to support the research of this condition. The aim of this study is to describe the racial and ethnic distribution of patients enrolled in the BRR and evaluate factors associated with healthcare disparities within manifestations of and/or the care delivered to this population. At the time of this study, 3600 patients with bronchiectasis and/or NTM were enrolled in the BRR. Of those, 3510 participants were included in these analyses. The population was predominantly non-HispanicWhite (n = 3143, 89.5%), followed by Hispanic or Latino (n = 149, 4.3%), Asian (n = 130, 3.7%) and non-Hispanic Black (n = 88, 2.5%) participants. Testing for cystic fibrosis, immunoglobulin deficiency, and mycobacteria was not different between races, but non-Hispanic Black patients were tested less frequently for alpha-1 antitrypsin (A1AT) deficiency compared to other groups (P = 0.01). The four groups did not differ in the proportion of Pseudomonas aeruginosa or Hemophilus influenzae. There was no statistically significant difference in use of high-frequency chest wall oscillation, pulmonary rehabilitation services, or suppressive macrolide treatment across the groups (P > 0.05). There is a disproportionately high percentage of non-Hispainc White patients compared to non-Hispanic Black patients and Hispanic or Latino patients in the BRR. However, we found an overall similarity of care of BRR patients, regardless of racial and ethnic group.

Epicardial slices: an innovative 3D organotypic model to study epicardial cell physiology and activation.

The epicardium constitutes an untapped reservoir for cardiac regeneration. Upon heart injury, the adult epicardium re-activates, leading to epithelial-to-mesenchymal transition (EMT), migration, and differentiation. While interesting mechanistic and therapeutic findings arose from lower vertebrates and rodent models, the introduction of an experimental system representative of large mammals would undoubtedly facilitate translational advancements. Here, we apply innovative protocols to obtain living 3D organotypic epicardial slices from porcine hearts, encompassing the epicardial/myocardial interface. In culture, our slices preserve the in vivo architecture and functionality, presenting a continuous epicardium overlaying a healthy and connected myocardium. Upon thymosin ß4 treatment of the slices, the epicardial cells become activated, upregulating epicardial and EMT genes, resulting in epicardial cell mobilization and differentiation into epicardial-derived mesenchymal cells. Our 3D organotypic model enables to investigate the reparative potential of the adult epicardium, offering an advanced tool to explore ex vivo the complex 3D interactions occurring within the native heart environment.

Overexpression of miR-210 and its significance in ischemic tissue damage.

Hypoxia-induced miR-210 displays a pro-survival, cytoprotective and pro-angiogenic role in several in vitro systems. In vivo, we previously found that miR-210 inhibition increases ischemic damage. Here we describe the generation of a versatile transgenic mouse model allowing the evaluation of miR-210 therapeutic potential in ischemic cardiovascular diseases. We generated a Tet-On miR-210 transgenic mouse strain (TG-210) by targeted transgenesis in the ROSA26 locus. To functionally validate miR-210 transgenic mice, hindlimb ischemia was induced by femoral artery dissection. Blood perfusion was evaluated by power Doppler while tissue damage and inflammation were assessed by histological evaluation. We found that miR-210 levels were rapidly increased in TG-210 mice upon doxycycline administration. miR-210 overexpression was maintained over time and remained within physiological levels in multiple tissues. When hindlimb ischemia was induced, miR-210 overexpression protected from both muscular and vascular ischemic damage, decreased inflammatory cells density and allowed to maintain a better calf perfusion. In conclusion, we generated and functionally validated a miR-210 transgenic mouse model. Albeit validated in the context of a specific cardiovascular ischemic disease, miR-210 transgenic mice may also represent a useful model to assess the function of miR-210 in other physio-pathological conditions.

Contribution of pericyte paracrine regulation of the endothelium to angiogenesis.

During physiological development and after a stressor event, vascular cells communicate with each other to evoke new vessel formation-a process known as angiogenesis. This communication occurs via direct contact and via paracrine release of proteins and nucleic acids, both in a free form or encapsulated into micro-vesicles. In diseases with an altered angiogenic response, such as cancer and diabetic vascular complications, it becomes of paramount importance to tune the cell communication process. Endothelial cell growth and migration are essential processes for new vessel formation, and pericytes, together with some classes of circulating monocytes, are important endothelial regulators. The interaction between pericytes and the endothelium is facilitated by their anatomical apposition, which involves endothelial cells and pericytes sharing the same basement membrane. However, the role of pericytes is not fully understood. The characteristics and the function of tissue-specific pericytesis are the focus of this review. Factors involved in the cross-talk between these cell types and the opportunities afforded by micro-RNA and micro-vesicle techniques are discussed. Targeting these mechanisms in pathological conditions, in which the vessel response is altered, is considered in relation to identification of new therapies for restoring the blood flow.

Early results of synchronous carotid endarterectomy and off-pump coronary revascularization.

AIM: This study reports results of synchronous carotid endarterectomy (CEA) and off-pump coronary artery bypass grafting (CABG) in further support of the hypothesis that carotid and coronary artery revascularization can be safely performed in most patients. METHODS: The series includes 74 consecutive patients underwent synchronous CEA and off-pump CABG (group A) compared with 50 patients undergoing synchronous CEA and on-pump CABG (group B). Primary endpoint of this study are death, stroke, perioperative myocardial infarction and need for repeated revascularization within 30 days of the procedures. The secondary endpoint includes local and systemic complications. RESULTS: No stroke was observed in group A. Ipsilateral minor stroke occurred in two patients of group B (4%). Two deaths within 30 days were observed in group A (2.7%) compared with 4 deaths in group B (8%). Combined stroke/death rate at 30 days was 2.7% in group A compared with 12% in group B (P< 0.05). No significant differences in myocardial infarction, local and systemic complications were observed. CONCLUSION: Synchronous CEA and off-pump CABG may reduce the high surgical risk of patients who actually require combined carotid and coronary revascularization. This opinion has to be substantiated by larger studies and randomized trial.

Cardiac protection by volatile anaesthetics: a multicentre randomized controlled study in patients undergoing coronary artery bypass grafting with cardiopulmonary bypass.

BACKGROUND AND OBJECTIVES: To evaluate the effects of total intravenous anaesthesia vs. volatile anaesthesia on cardiac troponin release in coronary artery bypass grafting with cardiopulmonary bypass, we performed a multicentre randomized controlled study to compare postoperative cardiac troponin release in patients receiving two different anaesthesia plans. METHODS: We randomly assigned 75 patients to propofol (intravenous anaesthetic) and 75 patients to desflurane (volatile anaesthetic) in addition to an opiate-based anaesthesia for coronary artery bypass grafting. Peak postoperative troponin I release was measured as a marker of myocardial necrosis. RESULTS: There was a significant (P < 0.001) difference in the postoperative median (25th-75th percentiles) peak of troponin I in patients receiving propofol 5,5 (2,3-9,5) ng dL(-1) when compared to patients receiving desflurane 2,5 (1,1-5,3) ng dL(-1). The median (interquartile) troponin I area under the curve analysis confirmed the results: 68 (30.5-104.8) vs. 36.3 (17.9-86.6) h ng dL(-1) (P = 0.002). Patients receiving volatile anaesthetics had reduced need for postoperative inotropic support (24/75, 32.0% vs. 31/75, 41.3%, P = 0.04), and tends toward a reduction in number of Q-wave myocardial infarction, time on mechanical ventilation, intensive care unit and overall hospital stay. CONCLUSIONS: Myocardial damage measured by cardiac troponin release could be reduced by volatile anaesthetics in coronary artery bypass surgery.

Septal dissection and rupture evolved as an inferobasal pseudoaneurysm.

We report two cases of postinfarction dissecting hematoma of the interventricular septum with restrictive ventricular septal defect that evolved as an inferobasal pseudoaneurysm. The difficult anatomical pattern was assessed by two-dimensional (2-D) echocardiography with Doppler and color analysis, left ventriculography and perioperative transoesophageal echo. Because the patient had no signs of heart failure, the surgical repair was successfully delayed until the dissecting tissue became fibrotic. Problems of diagnosis, decision making and surgical management are discussed.

Left ventricular mass reduction after aortic valve replacement: homografts, stentless and stented valves.

BACKGROUND: We studied the effect of four different types of prosthetic aortic valves on time course and extent of regression of left ventricular hypertrophy after aortic valve replacement for aortic stenosis. METHODS: Four groups of 10 patients each were randomly assigned to receive: (1) aortic homograft preserved in antibiotic solution at 4 degrees C, (2) Toronto stentless porcine valve, (3) Medtronic Freestyle stentless valve, or (4) Medtronic Intact aortic valve. The left ventricular mass index, effective orifice area index, and peak and mean transaortic gradients were measured by Doppler echocardiography before the operation and 8 months postoperatively. RESULTS: The hemodynamic performance indices were much better for the homograft and stentless valves than for the stented one. The absolute left ventricular mass index reduction was greater in the homograft group compared with the Intact (p = 0.0004) and Toronto (p = 0.007) groups. The extent of percent left ventricular mass index reduction was greater only in the homograft group versus Intact group (p = 0.005). The multilinear regression analysis showed that the only predictors of a larger percentage of left ventricular mass index reduction were the homograft type, a higher valve size index, and a higher preoperative left ventricular mass index. CONCLUSIONS: When a stentless or homograft aortic valve was used instead of a stented valve to replace a stenotic aortic valve there was more complete or at least faster regression of left ventricular hypertrophy. The hemodynamic performance of stentless porcine valves was similar to that of aortic homografts, nevertheless the aortic homografts preserved in antibiotic solution offered a faster regression of left ventricular hypertrophy during the same period of time.

[Aortic valve replacement in patients over 70: a Doppler echocardiographic study]. / La sostituzione valvolare aortica in pazienti ultrasettantenni: studio ecocardiografico Doppler.

Aortic valve disease is known to be the most frequent valvular disease in the elderly and aortic valve replacement is often the best therapeutic strategy. Hemodynamic performance of prostheses is critical in this subset of patients to ensure an optimal quality of life. Moreover, old patients with small aortic ostia are getting more and more common in clinical practice, making often necessary to implant small prostheses. If a significant pressure drop is not achieved, hypertrophy persists and left ventricular function may not improve. Such conditions have not yet been extensively studied in the elderly. The aim of this study was firstly to assess echocardiographically the performance of aortic prosthetic heart valves in old patients (> or = 70 years) and compare the results obtained in patients with prostheses of different type and size, and secondly to evaluate the postoperative changes in left ventricular hypertrophy and function in a subset of patients with isolated or prevalent aortic stenosis. One hundred fifty-one patients were initially considered; global mortality was 9.3% at 20 +/- 12 months from intervention. In the 75 patients with a postoperative echocardiogram, transprosthetic gradient was 27 +/- 12 (max) and 15.1 +/- 6.6 (mean) mmHg. Mean functional prosthetic area (FPA) was 1.5 +/- 0.5 cm2. No statistically significant differences could be demonstrated between mechanical and biological prostheses. Three groups were identified, according to prosthetic size (Group 1: diameter < 23 mm, Group 2: diameter 23 mm, Group 3: diameter > 23 mm). Among groups, max and mean gradients as well as FPA were found to be significantly different. Respectively max gradient was 33.2 +/- 13, 26 +/- 11, 20.2 +/- 7.2 mmHg (p < 0.05), mean gradient was 17.2 +/- 6.1, 15.4 +/- 7.6, 11.7 +/- 4.3 mmHg (p < 0.01) and FPA was 1.2 +/- 0.3, 1.5 +/- 0.3, 1.8 +/- 0.7 cm2 (p < 0.05 between Group 1 and Group 3). In a subgroup of 31 patients with isolated or prevalent aortic stenosis, a significant interventricular septal thickness reduction was found postoperatively (14.3 +/- 2.3 vs 12.6 +/- 8.0 mm, p < 0.001). Posterior wall thickness decreased similarly, but to a lesser extent; left ventricular diameters and myocardial mass also significantly decreased (left ventricular mass: 186 +/- 45 vs 146 +/- 38 g/m2, p < 0.001). When prosthetic size was considered, septal thickness reduction was more evident in Group 1 and Group 2 (p < 0.05 and p < 0.01). On the contrary, a significant improvement in left ventricular diameters was observed only in Group 3 (p < 0.05). Left ventricular mass decreased significantly in Group 2 and Group 3 (p < 0.01 and p < 0.05). Such improvements could be demonstrated only in those patients (79%) who showed at least a 50% reduction in the transvalvular gradient. In this subset, left ventricular function also significantly improved (fractional shortening: 29 +/- 0.7 vs 33 +/- 0.7%, p < 0.02). In conclusion, aortic valve replacement in the elderly is a safe and effective therapeutic strategy. In patients with small aortic prostheses, the transvalvular gradient was found to be slightly but significantly higher as compared to that of larger prostheses. However, left ventricular function was good and similar in all subgroups. No significant differences were found between mechanical and biological prostheses. In old patients with isolated or prevalent aortic stenosis a significant reduction in left ventricular hypertrophy and mass is observed within 2 years from intervention. An increase in myocardial contractility can also be expected, if at least a 50% reduction in transvalvular gradient is obtained.

Posttraumatic left ventricular pseudoaneurysm due to intramyocardial dissecting hematoma.

A left ventricular aneurysm can develop in patients sustaining blunt chest injury. This condition has been attributed to myocardial contusion or to a direct vascular lesion leading to myocardial necrosis. We report the case of a pseudoaneurysm resulting from myocardial dissection beginning from a small tear in the endocardial wall. Successful surgical exclusion of the pseudoaneurysm by endoaneurysmal patch closure of the communications between the aneurysm and the left ventricular cavity is described.

Left main coronary artery atresia: literature review and therapeutical considerations.

OBJECTIVE: Left main coronary artery atresia is a rare coronary anomaly in which there is no left coronary ostium, the proximal left main trunk ends blindly, blood flows from the right coronary artery to the left via small collateral arteries and retrogradely in at least one of the left-sided arteries. Since published case reports are few and rather scattered, no comprehensive information about this uncommon anomaly is available. METHODS: A through search for published cases of left main coronary atresia was performed in the major medical journals by electronic (MEDLINE and INTERNET) and hand-scanning. RESULTS: The authors found 28 cases of left main atresia (including two from their own experience), 15 of which were pediatric; five of these cases had associated cardiac anomalies. While pediatric patients were usually overtly symptomatic early in their life (syncope, dyspnea, sudden death, failure to thrive, infarction, ventricular tachycardia), adult patients began showing symptoms (angina, dyspnea, sudden death) only at an advanced age; associated coronary atherosclerosis seemed to be uncommon, though (2/13 adult patients, 15%). We know of only one asymptomatic patient, a 76-year old lady who had died of unrelated causes; in her case left main atresia was an unforeseen autopsy finding. Four untreated patients had died suddenly; most of the others were highly symptomatic and required surgical therapy, usually as direct coronary artery revascularization via one or more saphenous vein or mammary artery grafts to the left-sided arteries; all revascularized patients were reported to be alive and well; in one pediatric case the left main coronary artery was reconstructed using an aortic wall baffle, with a good result. In contrast, the outcome of patients who did not receive revascularization has been poor. CONCLUSION: In light of the favorable results obtained by surgical therapy, the authors endorse prompt coronary artery revascularization for all patients with left main coronary artery atresia.

[Structural and morphometric analysis of the internal mammary artery used in coronary bypass surgery]. / Analisi strutturale e morfometrica dell'arteria mammaria interna utilizzata nel bypass coronarico.

The internal mammary artery is currently regarded as the optimal canal in coronary bypass surgery. Even if the motives for the excellent behaviour of this artery are still not fully clarified, the morphological and morphofunctional study of its wall can contribute to explain the clinical results obtained using this canal. In order to complete existing studies on this topic and to increase our knowledge of the structure of this artery, segments of internal mammary artery taken from patients undergoing coronary bypass surgery were analysed. Histological, immunohistochemical, histochemical and morphometrical tests were performed in these samples. The results of the tests underline the considerable complexity of the internal mammary artery whose walls appear to be rich in elastic fibres, divided into numerous lamellar structures concentric to the vasal lumen and without vasa vasorum in the tunica media given that this is adjacent to the tunica adventitia. Moreover, the marked presence of the NO-synthase enzyme, responsible for nitrogen monoxide synthesis, was observed in the endothelial layer and tunica media, as suggested by histochemical analysis. These data argue in favour of a structure able to resist the considerable hemodynamic stress to which the artery is subjected after bypass, a structure which is functionally well adapted to receive the majority of nutrition through its own lumen, and, lastly, a structure capable of self-regulation in response to the requirements made from time to time. These findings may further our understanding of the morphofunctional aspects of the internal mammary artery and may contribute to explaining the latter's relative immunity to atherosclerosis and, thus, its success in coronary bypass.

[Surgical revascularization of the myocardium for atresia of the left main coronary artery and atherosclerotic coronary disease]. / Rivascolarizzazione chirurgica del miocardio per atresia del tronco comune e coronaropatia aterosclerotica.

The authors report a rare case of atresia of the left main coronary artery in an adult patient, symptomatic for effort angina. At coronarography, the left main coronary artery was not found; instead, the arteries of the left coronary tree were filled via a single collateral vessel arising from the ostium of the right coronary artery and ending in the trunk of the left anterior descending artery. All left arteries had very narrow calibres, almost hypoplastic, while the right coronary artery had a normal calibre. All the principal arteries had important stenoses. The patient underwent complete cardiac revascularization, and, sixteen months later, is free from angina. Rest and stress myocardial scintigraphy, control coronary angiography and Doppler analysis of internal mammary artery flow demonstrated normal myocardial perfusion, adequate blood flow through the grafts and good runoff in the native vessels. Hence, the authors conclude that such patients should be referred for coronary artery revascularization, since surgical results are good and the small calibre of the left coronary arteries is no contraindication.