The Hard Lessons Learned by the COVID-19 Epidemic in Italy: Rethinking the Role of the National Health Care Service?

The dramatic events precipitated by the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) virus pandemic have highlighted the limitations and contradictions of our country's current health care delivery model plagued by the closure of healthcare delivery structures, staff reductions, privatizations and inadequate funding which have been affecting the Italian National Health System during the past 10 years. The COVID-19 epidemic has a hefty bill: thousands of deaths - mainly elderly, hospitals overwhelmed, residential assistance structures reaching their limits, sick people left alone and uncared in homes, the disruption in life habits and an altered daily way of living never experienced before; all have contributed into making the ongoing tragedy even more painful. Herewith, we present and discuss the information and reflections from our experiences and postulate the rethinking of the established socio-health policies not only in Italy but also in other western countries which have failed to curtail the epidemic via conventional management approaches.

Safe Reentry for False Aneurysm Operations in High-Risk Patients.

BACKGROUND: In the absence of a standardized safe surgical reentry strategy for high-risk patients with large or anterior postoperative aortic false aneurysm (PAFA), we aimed to describe an effective and safe approach for such patients. METHODS: We prospectively analyzed patients treated for PAFA between 2006 and 2015. According to the preoperative computed tomography scan examination, patients were divided into two groups according to the anatomy and extension of PAFA: in group A, high-risk PAFA (diameter ≥3 cm) developed in the anterior mediastinum; in group B, low-risk PAFA (diameter <3 cm) was situated posteriorly. For group A, a safe surgical strategy, including continuous cerebral, visceral, and coronary perfusion was adopted before resternotomy; group B patients underwent conventional surgery. RESULTS: We treated 27 patients (safe reentry, n = 13; standard approach, n = 14). Mean age was 60 years (range, 29 to 80); 17 patients were male. Mean interval between the first operation and the last procedure was 4.3 years. Overall 30-day mortality rate was 7.4% (1 patient in each group). No aorta-related mortality was observed at 1 and 5 years in either group. The Kaplan-Meier overall survival estimates at 1 and 5 years were, respectively, 92.3% ± 7.4% and 73.4% ± 13.4% in group A, and 92.9% ± 6.9% and 72.2% ± 13.9% in group B (log rank test, p = 0.830). Freedom from reoperation for recurrent aortic disease was 100% at 1 year and 88% at 5 years. CONCLUSIONS: The safe reentry technique with continuous cerebral, visceral, and coronary perfusion for high-risk patients resulted in early and midterm outcomes similar to those observed for low-risk patients undergoing conventional surgery.

A study of the mechanical properties of ePTFE suture used as artificial mitral chordae.

BACKGROUND AND AIM OF THE STUDY: We investigated the dimensional and mechanical properties of polyetetrafluorene (ePTFE) sutures used as artificial chordae during mitral valve repair. METHODS: Mechanical properties of ePTFE synthetic chordae tendineae were tested with a servo hydraulic testing machine. Several different lengths from 2 to 14 cm were studied under both single and multiple mechanical traction. RESULTS: The mechanical behavior of artificial chordae reveals that three centimeters is the length over which we observe a significant increase in stiffness. The chordae stiffness grows further at the length greater than seven centimeters following a low number of traction cycles. CONCLUSION: The increase of the length of artificial ePTFE chordae is accompanied by an increasing stiffness that compromises the long-term resistance of the chordae. ePTFE length can alter the performance of artificial chordae. This suggests that mitral valve repairs which anchor ePTFE neochordae to the ventricular apex may have less durability than when anchored to the tips of the papillary muscles.

Different expression and function of the endocannabinoid system in human epicardial adipose tissue in relation to heart disease.

BACKGROUND: The endocannabinoid system reportedly plays a role in the pathogenesis of cardiovascular diseases. This system is expressed also in adipose tissue, which could thus be involved in cardiac disorders through modulation of metabolically triggered inflammation. The current study aims to determine the relevance of the endocannabinoid system in epicardial adipose tissue in heart disease. METHODS: Expression of the endocannabinoid receptors CB1 and CB2, and of the endocannabinoid-degrading enzyme, fatty acid amidohydrolase, and activation of protein kinase A (PKA), phospholipase C (PLC), protein kinase C (PKC), endothelial nitric oxide synthase (eNOS) and inducible (i)NOS, and extracellular signal-regulated kinases 1 and 2 (ERK1/2) (a member of the reperfusion-injury salvage kinase pathway), were analyzed by Western blot in patients after coronary artery bypass surgery (ischemics; N = 18) or valve surgery (nonischemics; N = 15) and in preadipocytes isolated from epicardial adipose tissue. RESULTS: In ischemics, the CB1-to-CB2 expression ratio shifted toward CB1 and was accompanied by higher PKA activation. In contrast, in nonischemics, CB2, fatty acid amidohydrolase, PLC and PKC, and ERK1/2 were upregulated. Moreover, NO production and iNOS-to-eNOS ratios were higher in preadipocytes from ischemics. CONCLUSIONS: These results show a different modulation and functioning of the endocannabinoid system in ischemics compared with nonischemics. Hence, while CB2, PLC and PKC, ERK1/2, and eNOS are more strongly expressed in patients without ischemic heart disease, high CB1 and PKA expression is associated with low survival intracellular pathway activation and high iNOS activation in ischemic heart disease patients. The changes in the endocannabinoid system in ischemics may contribute to cardiac dysfunction and therefore represents a potential therapeutic target.

Mitral valve repair or replacement for ischemic mitral regurgitation? The Italian Study on the Treatment of Ischemic Mitral Regurgitation (ISTIMIR).

OBJECTIVE: It is uncertain whether mitral valve replacement is really inferior to mitral valve repair for the treatment of chronic ischemic mitral regurgitation. This multicenter study aimed at providing a contribution to this issue. METHODS: Of 1006 patients with chronic ischemic mitral regurgitation and impaired left ventricular function (ejection fraction < 40%) operated on at 13 Italian institutions between 1996 and 2011, 298 (29.6%) underwent mitral valve replacement whereas 708 (70.4%) received mitral valve repair. Propensity scores were calculated by a nonparsimonious multivariable logistic regression, and 244 pairs of patients were matched successfully using calipers of width 0.2 standard deviation of the logit of the propensity scores. The postmatching median standardized difference was 0.024 (range, 0-0.037) and in none of the covariates did it exceed 10%. RESULTS: Early deaths were 3.3% (n = 8) in mitral valve repair versus 5.3% (n = 13) in mitral valve replacement (P = .32). Eight-year survival was 81.6% ± 2.8% and 79.6% ± 4.8% (P = .42), respectively. Actual freedom from all-cause reoperation and valve-related reoperation were 64.3% ± 4.3% versus 80% ± 4.1%, and 71.3% ± 3.5% versus 85.5% ± 3.9 in mitral valve repair and mitral valve replacement, respectively (P < .001). Actual freedom from all valve-related complications was 68.3% ± 3.1% versus 69.9% ± 3.3% in mitral valve repair and mitral valve replacement, respectively (P = .78). Left ventricular function did not improved significantly, and it was comparable in the 2 groups postoperatively (36.9% vs 38.5%, P = .66). At competing regression analysis, mitral valve repair was a strong predictor of reoperation (hazard ratio, 2.84; P < .001). CONCLUSIONS: Mitral valve replacement is a suitable option for patients with chronic ischemic mitral regurgitation and impaired left ventricular function. It provides better results in terms of freedom from reoperation with comparable valve-related complication rates.

Subacute endocarditis caused by Yersinia enterocolitica: a case report.

Yersinia enterocolitica is an unusual cause of septicaemia, usually occurring in immunocompromised hosts. Endocardial involvement is rare and generally presents as acute endocarditis. We describe the case of a 73-y-old woman, apparently without risk factors for endocarditis, admitted to hospital for persistent fever of unknown origin, arthralgia, and weight loss. Y. enterocolitica was isolated from blood and urine cultures, and echocardiography showed a pedunculated vegetation attached to the non-coronary cusp of the aortic valve. Symptoms and fever resolved after 3 days of intravenous cefotaxime plus amikacin, which were continued for the 2 weeks of her hospital stay; this treatment was followed by intravenous ceftriaxone after discharge. We hypothesized that a chemotherapy course administered 2 months previously for breast cancer might have been a predisposing factor for the Y. enterocolitica valvular infection and that immune system recovery contributed to mitigate the clinical presentation as subacute endocarditis.

Relationship between left atrial volume and atrial fibrillation following coronary artery bypass grafting.

BACKGROUND: Atrial fibrillation (AF) is a common complication of coronary artery bypass grafting (CABG). However, limited information is available about the role of preoperative echocardiographic left atrial evaluation to predict AF occurrence after CABG. Thus, we prospectively compared the ability of echocardiographic measurements of left atrial volume to predict AF in this setting. METHODS: From January to December 2009, 220 patients (75% males, 66.8 ± 10.0 years) met the inclusion criteria of our study (isolated and elective CABG, no valve surgery, no permanent AF, or other chronic atrial arrhythmias). The day before CABG a complete echocardiographic evaluation was performed with left atrial volume measurements. The primary endpoint of the study was postoperative AF (POAF) lasting >30 seconds. RESULTS: POAF was observed in 61 patients (27.7%). POAF patients showed increased left atrial M-mode anteroposterior dimension (41.2 ± 6.4 mm vs. 43.6 ± 7.3 mm; p = 0.020) and increased left atrial volume (59.0 ± 18.3 mL vs. 70.6 ± 28.1 mL; p = 0.0004). Left atrial volume was an independent risk factor for POAF (OR 10.03; 95% CI 10.01 to 10.05; p = 0.01), along with postoperative bleeding with hemoglobin levels below 8 g/dL (OR 20.84; 95% CI 10.12 to 70.19; p = 0.03) and preoperative left ventricular ejection fraction below 40% (OR 10.08; 95% CI 10.01 to 10.15; p = 0.02). Conversely, preoperative statin therapy exerted a protective role (OR 0.30; 95% CI 0.12 to 0.74; p = 0.009). CONCLUSION: Preoperative echocardiographic evaluation of patients with isolated CABG demonstrated that left atrium volume measurements were independently correlated to the occurrence of POAF. Further investigations should focus on the opportunity to target prophylactic antiarrhythmic treatments to patients with large left atrial volumes.

Intracoronary levosimendan prevents myocardial ischemic damages and activates survival signaling through ATP-sensitive potassium channel and nitric oxide.

OBJECTIVE: Levosimendan has been reported to exert cardioprotection. In this study, we have examined the cardiac effects of different doses of intracoronary levosimendan on ischemia/reperfusion injuries, and the involvement of K(ATP) channels and nitric oxide (NO). METHODS: The experiments were performed in a total of 56 anesthetized pigs. In 21 pigs, 1.5, 5 and 12 µg min(-1) levosimendan was infused over 15 min into the coronary artery at the onset of 1 h reperfusion following 2-h ischemia and the effects on cardiac function, infarcted area, and on apoptosis/autophagy were examined. In addition, the activation of Akt and extracellular receptor kinase (ERK) was analyzed. The findings were compared with those obtained in a further 14 pigs where the highest dose levosimendan was infused after glibenclamide and l-nitro-arginine methyl ester (l-NAME). RESULTS: Intracoronary 1.5, 5 and 12 µg min(-1) levosimendan caused an increase of segmental shortening, dP/dt(max) and cardiac output of 7.8%, 22.6%, and 31.6%; 7.6%, 16.9%, and 21.6%; 2.8%, 5.9%, and 6.2%, respectively, from values measured at the end of ischemia. The beneficial effects elicited by levosimendan were still evident at the end of reperfusion when the increase of segmental shortening, dP/dt(max) and cardiac output caused by the three doses of levosimendan amounted to 3.7%, 13.3%, and 16.5%; 1.5%, 9.4%, and 11%; 1.4%, 2.7%, and 3.9%, respectively. When doses of 5 and 12 µg min(-1) levosimendan were used, a reduction of infarcted area to about 69% and 67% of area at risk was observed, and was significantly different from that of about 79% measured in control animals. In addition, after intracoronary levosimendan, the inhibition of apoptosis and activation of autophagy and a dose-related increase of the level of phosphorylation of ERK and Akt were observed. These responses were completely prevented by glibenclamide and significantly reduced by l-NAME. CONCLUSIONS: The results of this study show that intracoronary levosimendan reduces cell death induced by ischemia/reperfusion in a dose-dependent manner and activates survival signaling through K(ATP) channel opening and NO. These findings support interesting implications for cardioprotection in interventional cardiology and cardiac surgery.

Double patch repair through a single ventriculotomy for ischemic ventricular septal defects.

We present a novel postinfarction ventricular septal defect repair, through a single ventriculotomy, using a biseptal double patch and gelatin-resorcinol-formaldehyde glue. This technique reduces the postoperative recurrence of ventricular septal defects by reducing the tension on the patch sutures and by preventing blood from infiltrating into the suture lines within the ventricular septal defect cavity.

Modulation of programmed forms of cell death by intracoronary levosimendan during regional myocardial ischemia in anesthetized pigs.

PURPOSE: Powerful mediators of programmed cell death, such as apoptosis and autophagy, can contribute to myocyte cell loss during pathological cardiac conditions. Levosimendan has been shown to exert beneficial hemodynamic effects in presence of global myocardial ischemia and heart failure through vasodilatation and increase of cardiac contractility. Recently, the intracoronary administration of a bolus levosimendan was found to exert favourable cardiac anti-stunning effects without lowering arterial pressure, which limits the use of levosimendan mainly in coronary artery disease. Here we tested whether the intracoronary administration of levosimendan can beneficially modulate programmed cell death in acute regional myocardial ischemia. METHODS: Acute regional myocardial ischemia was induced in 20 anaesthetized pigs and intracoronary levosimendan 15 min bolus administration was started 4 h afterwards. The effects of levosimendan on coronary blood flow and cardiac function were evaluated and myocardial biopsies were examined for criteria of autophagy and apoptosis. RESULTS: The administration of levosimendan caused a significant increase of coronary blood flow (p < 0.05) in absence of changes in cardiac function. Moreover, levosimendan prevented the down-regulation of the anti-apoptotic gene, Bcl-2, and the up-regulation of the apoptotic markers Bax and cytochrome c, which resulted in a reduced expression of TUNEL fragmented nuclei (p < 0.05). Furthermore, levosimendan maintained Beclin 1 at 4 h and potentiated LC3 II expression, these results being consistent with autophagy activation. CONCLUSIONS: Such effects of intracoronary levosimendan bolus administration during regional myocardial ischemia indicate the occurrence of cardio-protection by modulation of programmed form of cell death.

Modulation of calcium movements by urocortin II in endothelial cells.

BACKGROUND: In endothelial cells urocortin II has recently been found to activate nitric oxide synthase through cAMP-dependent and Ca(2+)-related pathway. AIM: The present study was therefore planned to determine the mechanisms of urocortin II effect on Ca(2+) movements. METHODS: In Fura-2 loaded porcine aortic endothelial cells (PAE), the effects of urocortin II on [Ca(2+)]c were analyzed and compared with those of various K(+) channels agonists/antagonists. RESULTS: In Fura-2 loaded PAE, urocortin II promoted a transient increase of [Ca(2+)]c mainly originating from an intracellular pool sensitive to thapsigargin and slightly from the extracellular space. In addition, urocortin II caused the hyperpolarization of plasma membrane through the opening of K(+) channels, which contributed to the increased [Ca(2+)]c. These effects were abolished by the corticotropin releasing factor receptors (CRFR2) blocker, the adenylyl cyclase and Ca(2+)-calmodulin-kinase (CaMKII) inhibitors and by blockers of K(+) channels. In addition, in PAE cultured in Na(+)-free medium or loaded with the plasma-membrane Ca(2+) pump inhibitor the urocortin II-evoked Ca(2+) transient was slower. CONCLUSION: The results obtained show that urocortin II affects intracellular Ca(2+) homeostasis in PAE by both promoting a discharge of intracellular pool and by interfering with the operation of store-dependent channels through CRFR2-cAMP-CaMKII related signalling and K(+) channels opening.

Cellular pathology of mitral valve prolapse.

BACKGROUND: Mitral valve prolapse (MVP) is the most frequent cause of chronic, pure, and isolated mitral regurgitation, and is estimated to affect more than 144 million individuals worldwide. This short review focuses in particular on the structural and cellular aspects of MVP in humans. The key microscopic change in MVP appears to occur in the fibrosa, on which the structural integrity of the entire valve depends. Recent discoveries showed that proteoglycans may play an active role in both MVP initiation and/or progression together with valvular interstitial cells. A full understanding of the cellular basis of MVP goes beyond a mere mechanicistic description of the disease, involving the transformation of resting fibroblasts into activated myofibroblasts. CONCLUSIONS: Mitral valve could represent therefore an ideal environment to study early transformation phases of fibroblasts toward a protomyofibroblast phenotype.

Intracoronary intermedin 1-47 augments cardiac perfusion and function in anesthetized pigs: role of calcitonin receptors and beta-adrenoreceptor-mediated nitric oxide release.

Systemic intermedin (IMD)1-47 administration has been reported to result in vasodilation and marked hypotension through calcitonin-related receptor complexes. However, its effects on the coronary circulation and the heart have not been examined in vivo. The present study was therefore planned to determine the primary in vivo effect of IMD1-47 on coronary blood flow and cardiac function and the involvement of the autonomic nervous system and nitric oxide (NO). In 35 anesthetized pigs, IMD1-47, infused into the left anterior descending coronary artery at doses of 87.2 pmol/min, at constant heart rate and arterial blood pressure, augmented coronary blood flow and cardiac function. These responses were graded in a further five pigs by increasing the infused dose of IMD1-47 between 0.81 and 204.1 pmol/min. In the 35 pigs, the blockade of cholinergic receptors (intravenous atropine, 5 pigs), alpha-adrenoceptors (intravenous phentolamine, 5 pigs), and beta1-adrenoceptors (intravenous atenolol, 5 pigs) did not abolish the cardiac response to IMD1-47, the effects of which were prevented by blockade of beta2-adrenoceptors (intravenous butoxamine, 5 pigs), NO synthase (intracoronary N(omega)-nitro-l-arginine methyl ester, 5 pigs), and calcitonin-related receptors (intracoronary CGRP8-37/AM22-52, 10 pigs). In porcine coronary endothelial cells, IMD1-47 induced the phosphorylation of endothelial NO synthase and NO production through cAMP signaling leading to ERK, Akt, and p38 activation, which was prevented by the inhibition of beta2-adrenoceptors, calcitonin-related receptor complexes, and K+ channels. In conclusion, IMD1-47 primarily augmented coronary blood flow and cardiac function through the involvement of calcitonin-related receptor complexes and beta2-adrenoreceptor-mediated NO release. The intracellular signaling involved cAMP-dependent activation of kinases and the opening of K+ channels.

Impact of prosthetic mitral rings on aortomitral apparatus function: a cardiac magnetic resonance imaging study.

BACKGROUND: The circumference of the aortic annulus adjusts proportionally with changes in left ventricular volume. These dimensional changes in the aortic annulus improve the left ventricular outflow tract (LVOT) hemodynamics and enhance the anterior mitral valve leaflet (AML) movement. In this study, we investigated the impact of circumferential and partial circumference prosthetic mitral rings on aortomitral apparatus function. METHODS: Forty patients who underwent coronary artery bypass graft surgery and restrictive annuloplasty of the mitral valve annulus through either a partial circumference flexible ring (group A = 20 patients) or a circumferential rigid ring (group B = 20 patients) were evaluated using cardiac magnetic resonance imaging. Imaging was performed at the end of a 2-year follow-up period. Variations in LVOT diameter, transmitral valve gradient, and effective mitral valve area were measured and compared. RESULTS: Mean variation in LVOT diameter was significantly higher in group A compared with group B (12.7% +/- 4% versus 3.6% +/- 5%, p = 0.0005). Transmitral valve gradient was higher in group B than in group A (6.2 +/- 3 mm Hg versus 4.6 +/- 2 mm Hg, p = 0.007), whereas effective mitral valve area was larger in group A than group B (3.9 +/- 4 cm(2) versus 3.1 +/- 6 cm(2), p = 0.009). The long-axis cardiac magnetic resonance imaging of patients in group B demonstrated that movement at the base of the AML was hindered with the AML pivotal point appearing to shift posteriorly. CONCLUSIONS: This study demonstrated that the use of circumferential annular rings significantly impairs overall aortomitral apparatus function by reducing outflow diameter and AML movement.

Urocortin II induces nitric oxide production through cAMP and Ca2+ related pathways in endothelial cells.

BACKGROUND: Urocortin II has previously been shown in anesthetized pigs to increase coronary blood flow through activation of the endothelial nitric oxide synthase (eNOS) pathway and involvement of the subtype 2 of corticotropin releasing factor receptors (CRFR2). However, little information has been available regarding the intracellular signalling through these receptors and leading to the release of nitric oxide (NO). AIM: The present study was therefore planned to determine the mechanism involved in such signalling. METHODS: In porcine aortic endothelial cells (PAE) the effects of urocortin II on NO production and ERK, Akt, p38 and eNOS phosphorylation were examined in absence or presence of the adenylyl cyclase agonist forskolin and antagonist 2'5' dideoxyadenosine, the Ca2+ ionophore A23187, the Ca2+-calmodulin-kinase inhibitor KN93, the CRFR2 blocker astressin 2B and of the protein kinases specific inhibitors UO126, wortmannin and SB203580. RESULTS: Urocortin II caused a significant increase of NO production, which was amplified by forskolin and A23187 (P <0.05). All effects of urocortin II were abolished by l-NAME, 2'5' dideoxyadenosine, KN93, astressin 2B and by pre-treatment of cells with UO126, wortmannin and SB203580. Western Blot analysis confirmed the involvement of ERK, Akt and p38 in the eNOS activation. CONCLUSION: In PAE urocortin II interaction with CRFR2 caused a cAMP-dependent and Ca2+-related phoshorylation of ERK, Akt and p38 leading to eNOS activation.

Intracoronary genistein acutely increases coronary blood flow in anesthetized pigs through beta-adrenergic mediated nitric oxide release and estrogenic receptors.

Various studies have suggested that the phytoestrogen genistein has beneficial cardioprotective and vascular effects. However, there has been scarce information regarding the primary effect of genistein on coronary blood flow and its mechanisms including estrogen receptors, autonomic nervous system, and nitric oxide (NO). The present study was planned to determine the primary effect of genistein on coronary blood flow and the mechanisms involved. In anesthetized pigs, changes in left anterior descending coronary artery caused by intracoronary infusion of genistein at constant heart rate and arterial pressure were assessed using ultrasound flowmeters. In 25 pigs, genistein infused at 0.075 mg/min increased coronary blood flow by about 16.3%. This response was graded in a further five pigs by increasing the infused dose of the genistein between 0.007 and 0.147 mg/min. In the 25 pigs, blockade of cholinergic receptors (iv atropine; five pigs) and alpha-adrenergic receptors (iv phentolamine; five pigs) did not abolish the coronary response to genistein, whose effects were prevented by blockade of beta(2)-adrenergic receptors (iv butoxamine; five pigs), nitric oxide synthase (intracoronary N(omega)-nitro-L-arginine methyl ester; five pigs) and estrogenic receptors (ERs; ERalpha/ERbeta; intracoronary fulvestrant; five pigs). In porcine aortic endothelial cells, genistein induced the phosphorylation of endothelial nitric oxide synthase and NO production through ERK 1/2, Akt, and p38 MAPK pathways, which was prevented by the concomitant treatment by butoxamine and fulvestrant. In conclusion, genistein primarily caused coronary vasodilation the mechanism of which involved ERalpha/ERbeta and the release of NO through vasodilatory beta(2)-adrenoreceptor effects.

Intracoronary infusion of levosimendan to treat postpericardiotomy heart failure.

Systemic hypotension limits the intravenous use of levosimendan, particularly in coronary disease. Published reports show that the intracoronary administration of levosimendan in animal models causes an increase of coronary blood flow without systemic hypotension. In this case report, the intracoronary administration of levosimendan bolus in a 74-year-old man with postpericardiotomy heart failure elicited beneficial cardiac effects, increasing both systolic and diastolic functions and blood flow in all of the grafts. No changes of heart rate and systemic arterial blood pressure were observed.

Combined minimally invasive coronary bypass surgery and left pulmonary lobectomy.

Two patients underwent combined heart and lung surgery performed through a limited left anterior thoracotomy. Good exposure of the left pulmonary hilum and the left anterior descending artery was obtained, allowing left upper lobectomy combined with off-pump coronary bypass grafting. This approach avoids potential complications due to sternotomy, staged operations, and cardiopulmonary bypass. These cases show that a limited thoracotomy allows safe and effective combined lung and cardiac surgery in carefully selected patients.

Use of the inferior epigastric artery for CABG.

Presentation of the inferior epigastric artery as conduit for coronary artery bypass grafting (CABG): harvesting, use and results.