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Background: Health systems worldwide have been overburdened by the "COVID-19 surge". Consequently, strategies to remodulate non-COVID medical and surgical care had to be developed. Knowledge of the impact of COVID surge on cardiac surgery practice is mainstem. Present study aims to evaluate the regional practice pattern during lockdown in Campania. Methods: A multicenter regional observational 26-question survey was conducted, including all adult cardiac surgery units in Campania, Italy, to assess how surgical practice has changed during COVID-19 national lockdown. Results: All centers adopted specific protocols for screening patients and personnel. A significant reduction in the number of dedicated intensive care unit (ICU) beds (-30.0%±38.1%, range: 0-100%) and cardiac operating rooms (-22.2%±26.4%, range: 0-50%) along with personnel relocation to other departments was disclosed (anesthesiologists -5.8%±11.1%, range: 0-33.3%; perfusionists -5.6%±16.7%, range: 0-50%; nurses -4.8%±13.2%, range: 0-40%; cardiologists -3.2%±9.5%, range: 0-28.6%). Cardiac surgeons were never reallocated to other services. Globally, we witnessed dramatically lower adult cardiac surgery case volumes (335 vs. 667 procedures, P

In 1981, Weinsier and Krumdieck described death resulting from overzealous total parenteral nutrition in two chronically malnourished, but stable, patients given aggressive total parenteral nutrition. This was the birth of what is now called the refeeding syndrome, a nutrition-related disorder associated with severe electrolyte disturbances. The purpose of this work is to demonstrate that refeeding syndrome was first described medically in Florence by Antonio Benivieni in 1507 in his book On Some Hidden and Remarkable Causes of Diseases and Cures. What we now know as refeeding syndrome was described in Report No. LVII of that book. The condition occurred as a result of the famine that affected Florence in 1496. The report documents (i) death due to starvation, (ii) death due to ingestion of deteriorated/toxic foods (inevitable in times of famine when healthy food is scarce), (iii) death caused by excessive food ingestion after forced, prolonged abstinence from food in adults, (iv) the death of breast-fed children and of their starved mothers eating to satiety and (v) the more favourable clinical outcome of those admitted to hospitals. It is possible that Benivieni was inspired by the description of the deaths of starved deserters in the book The Jewish War (70 AD) by the Romano-Jewish historian Flavius Josephus. Nevertheless, Benivieni wrote the first medical account of the central clinical features of refeeding syndrome. The main, broad clinical aspects of refeeding syndrome, described by Weinsier and Krumdieck in 1981, had been documented in medical literature four centuries earlier by Benivieni.

Background Scarce data are available on the long-term outcomes of different regimens of oral anticoagulation in an all comer population of patients undergoing aortic valve replacement with a bileaflet mechanical heart valve. Methods Outcomes of 88 patients discharged with a target INR of 2.0 (LOW-INR) were compared to 147 contemporary patients who have been recommended a target INR of 2.5 (CONV). Primary outcome was the composite of any thromboembolic or haemorrhagic events. Secondary outcomes were the individual components of the primary outcome, cardiovascular mortality and stroke. To reduce selection bias, a propensity weighted analysis was performed. Results After inverse probability of treatment weighting, the primary endpoint occurred in 0.7% of patient in the LOW-INR group and in 7.0% in the CONV group (p = .0255). Linearized event rate were significantly lower in the LOW-INR group (primary endpoint: rate difference − 12.0 per 1000 patient/years, p = .0052; haemorrhage: −5.8 per 1000 patient/years, p = .0330; neurological events: −7.6 per 1000 patient/years, p = .0140). Conventional target INR was associated with an increased hazard of the composite endpoint (HR 11.193, 95% CI 1.424–88.003, p = .0217). Conclusions Lowering the intensity of oral anticoagulation resulted in a relevant clinical benefit of reduced rates of haemorrhagic and neurological adverse events in the mid-term follow-up. This report confirms the safety profile of the low INR regimen in an all comer population undergoing aortic valve replacement with an Abbott mechanical valve.

Background and Aims The history of popes is an untapped treasure for historian of medicine for many reasons including i. number, ii. richness of documents available on their lives, iii. gender homogeneity, iiii. Long lasting lives, v. their affluence, vi. number of archiaters and personal physicians and surgeon of high professional level, viii. lived for many years in the same environment (Rome). Taking into consideration the availability of documents from 1100 onward (10 centuries of European history), popes represent good models to study a. the diseases of popes, b. social medicine, c. history of European universities and beyond, d. the history of hospitals, e. the history of archiaters, and f. the diseases of power. We are studying renal stone disease in popes from St Peter to John Paul II (34-2005). Preliminary results on gouty popes have been presented at ERA-EDTA Congress in Budapest and Milan pointing that out 20 gouty pontiffs 12 were stone formers or died because of its complications and 6 popes died because of non-gouty renal stones. The goal of this study is to provide an historical outline on renal stone disease in gouty and not gouty popes reigning in the years 537-1830 (from Vigilius―the 1st stone former pope―to Pius VIII, the last gouty pope). Methods We have studied history of popes on many books including those authored by von Ranke, von Pastor, de Novaes, Henrion, Paravicini Bagliani, Reardon, Rendina, Ceccarelli and Cosmacini. We have also studied the histories of archiaters of Platina and Marini. Results 25 out 193 popes were found gouty. Their mean age at start of pontiff was 64.6 and 70.6 at death, that nearly correspond to the time-course decline of age-related uric acid excretion. Thirteen of these popes had histories, signs, symptoms, and /or postmortem examination compatible with a diagnosis of renal stone disease. Six of them died with uremia, 4 were hydropics, 6 died because of stroke. In addition we have also outlined the narratives of 14 non gouty popes who had renal stone disease. The last pope affected by renal stone disease was Pius VI (1775-1779) , the last gouty popes was Pius VIII (1829-1830). Conclusion We have excluded from gouty popes Alexander VII erroneously defined gouty by Giuseppe De Novaes in 1815 and also excluded John IX since his gout―hypothesized by Wendy J Reardon in 1971―is not supported by documents. There are a few available specific data on the topic. A fundamental contribution was published by Lorenzo Gualino in 1934. He reported on 19 gouty popes, 12 of whom with histories or signs, or symptoms, and/or postmortem examination confirming renal stone diseaase. He also reported on 8 non gouty popes suffering from or died of renal stone disease. The findings should be matched also with those of Giovanni Ceccarelli (2001) who reported on 11 gouty popes 6 presenting with signs of stones and five dying anuric and/or hydropic. This paper includes on all popes with renal stone disease. Stroke and heart failure in gouty popes are a priority. In the last 2 centuries renal stone disease was no more a papal disease.

Background and Aims Pope Gregory I (Magnus)―born c.540 AD, Pope 580-604 AD―in a letter to Bishop Venanzio ofLuni (later venerated as a saint) wrote “I have been confined to bed for the last eleven months, because of pain and malaise and suffer because of goutand my life has been turned into a penitence for my sins thus I am waiting death as a physician who will give me health”. He was the first Pope to suffer of gout and opens a list including in the years 20 pontiffs that includes Sisinnius, (b.650, pope 21 day in 708); Boniface VI (b. 806, Pope 15 days in 886), Honorius IV (b.1210, Pope 1285-1287); Boniface VIII (b. 1230, Pope 1294-1303); Clement VI (b.1281,Pope 1342-1352), Nicholas V (b.1387, Pope 1447-1455); Pius II( b. 1405, Pope 1458-1464); Sixtus IV (b. 1414, Pope 1471-1474); Pius III (b.1440, Pope 26 days in 1503); Pius IV (b. 1499, Pope 1559-1565); Julius II (b. 1443, Pope 1503-1516); Julius III (b.1481, Pope 1550-1555); Clement VIII (b. 1536, Pope 1592- 1605); Clement X (b.1581, Pope 1670-1676); Innocent XI (b.1681, Pope 1676-1689); Innocent XII (b.1649, Pope 1676-2692); Innocent XIII (b.1655, Pope 1721-1724); Benedict XIV (b. 1765, Pope 1740-1758), and Pius VIII (b.1761, Pope 1829-1830). Their mean age at death was 69.4 years, the youngest being Sisinnius (59 years), the oldest being Clement X (96 years). Results Some popes were strong eaters like Boniface VIII. He was chronically affected by gout and renal stone disease and by the fear for death, and the search for therapies capable to prolong life. Cosmacini says “podagroso e gottoso”… the Pope is affected by arthritis and renal disease due to overalimentation very rich (straricca) in meat”. He enrolled various archiaters among them Taddeo Alderotti (1223-1295), Pietro da Abano (1257-1315), Anselmo da Bergamo (artisphysicae professor), Simone of Genova (author of Clavissanationis), Accursino from Pistoia, Manzia from Fabriano, Gugliemo da Brescia, Angelo da Camerino and Campano da Novara (Magister Campanus), the naturalist he too affected by renal stone disease. Julius III too was a strong eater (he loved fatty foods seasoned with garlic) as was Pius IV, the hard worker who everyday used to take a nap after lunch and a long walk later in the day. By contrast Nicholas V (his Pontiff saw in 1453 the Fall of Costantinople and the end of the Hundred Years War) was a sober eater and drinker as were Pius II who made use of simple common foods, little wine and slept up to 5-6 hours. Probably Nicholas V died uremic since his pale natural color switched into yellowish-brown (itaque ex naturali et subcandido in croceumsubcinericiumque color suusconversusest). Pius III “was a sober eater and drinker and used to dine every two days. Some of the above popes were patrons of universities (Boniface VIII, Nicholas V, Pius II), some were patrons of arts and science (Nicholas V, Sixtus IV). Boniface VIII is remembered for the Bulla detestandeferitatis (against dismemberment and evisceration of cadavers), issued on September 27, 1299). For thatBulla, during the subsequent centuries he was wrongly accused even by Herman Boerhaave and Albrecht von Haller to have retarded the advancement of medicine by impeding anatomical dissections. By contrast Sixtus IV is remembered not only for modernizing Rome and embelling it, but for the 1482 Breve to the University of Tubingen allowing―for teaching purposes ―dissection of dead bodies of people sentenced to death.

Deep sternal wound infections (DSWI), although an infrequent complication, significantly impair postoperative outcomes after coronary artery bypass grafting (CABG) surgery. Among several preventive strategies, topical antibiotic therapy immediately before sternal closure has been strongly advocated. In this retrospective analysis, the incidence of DSWI in 517 patients undergoing isolated CABG and receiving rifampicin irrigation of mediastinum, sternum and suprasternal tissues was compared to an historical consecutive cohort of 448 patients. To account for the inherent selection bias, a 1:1 propensity matched analysis was performed. Patients receiving topical rifampicin experienced significantly less occurrence of postoperative DSWI (0.2% vs 2.5%, p = 0.0016 in the unmatched analysis; 0.3% vs 2.1%, p = 0.0391 in the matched analysis). Intensive care unit stay, hospital stay, and operative mortality were similar between groups. This study shows that topical rifampicin in combination with commonly prescribed preventative strategies significantly reduces the incidence of DSWI to less than 0.3% in unselected patients undergoing a full median sternotomy for CABG. Further studies, including a larger number of patients and with a randomization design, would establish the potential preventative role of topical rifampicin in reducing the occurrence of DSWI.

Introduction: Thromboembolic complications are due to a complex interplay between patients’ characteristics, device features and anticoagulation intensity. Subtle design and material differences in available prostheses imply different susceptibility to thrombosis. This post hoc sub analysis of the LOWERING-IT database tested the safety and feasibility of a low-level oral anticoagulant regime in low-risk patients with aortic LivaNova prosthetic valve replacement. Methods: Study population included 148 patients randomized to LOW-INR group, and 144 patients randomized to CONVENTIONAL-INR group. The non inferiority of thromboembolic events between LOW-INR and CONVENTIONAL-INR groups was tested. Results: The two groups were well matched. Cumulative follow-up reached 1,545 patient/years. The mean INR was 1.91 ± 0.23 in the LOW-INR group, and 2.59 ± 0.26 in the CONVENTIONAL-INR group (P

To the Editor: Noninvasive ventilation (NIV) affects both the pulmonary and the cardiovascular systems. Indeed, it restores lung volume by opening atelectatic areas, increases alveolar ventilation, and reduces the work of breathing. Moreover, NIV reduces left ventricle afterload and improves

A U-shaped relationship between body mass index (BMI) and outcomes emerged after cardiac surgery. This review analyses the physio pathologic basis of obesity related complications and evaluates prognostic implications. Both leaner and morbid obese should be considered pre-operatively rather than reactively and, when referred for elective surgery, should undergo a focused metabolic status management, and a thorough evaluation of health status. Adherence to sound surgical principles, and tailored patient blood management and perioperative care are mandatory.

Background: Red blood cell (RBC) transfusion is a well-known predictor of acute kidney injury (AKI) and death after cardiac surgery. This study aimed to define the relationship between age and the need for RBC. Methods: Study population included 1,765 consecutive patients undergoing on-pump procedures from 2013 to 2015. The relationship between RBC transfusion and both survival and AKI, and any interaction with age was estimated. A propensity score for the likelihood to receive RBC transfusion was calculated using multivariate logistic regression analysis to adjust for the effect of confounding factors. A logistic estimation curve was developed to investigate the interaction between this score and age. Results: Patients receiving RBC transfusions had more comorbidities irrespective of age. Elderly patients underwent transfusion more often than younger patients with a 1.3-fold increase in the relative risk for transfusion. Age did not independently predict the need for RBC. AKI and mortality rates were significantly higher in transfused subsets irrespective of age. Conclusions: Comorbidity profile and not age per se confers an increased risk of transfusion.

Unresponsive pulmonary hypertension (PH) implies poor posttransplant outcomes. Data on late adaptation of the right ventricle (RV) are still few. This study evaluated three-yr RV function and remodeling, exercise capacity, and hemodynamic data in a selected group of patients initially disqualified because of PH. Between May 2005 and December 2009, 31 consecutive patients were qualified for oral sildenafil because of unresponsive PH at baseline right heart catheterization (RHC). After a 12-wk trial, RHC disclosed PH reversibility (mean PVR: 5.41 ± 3 Wood units, mean TPG 14.5 ± 5.6 mmHg, and mean systolic PAP 68.9 ± 15.1 mmHg), allowing listing even though as high-risk procedures. All patients underwent heart transplantation. RV failure developed in three patients (9.6%), and hospital mortality was 3.2%. Protocol RHC disclosed pulmonary hemodynamic profile normalization within the third postoperative month, allowing weaning from sildenafil in the 30 hospital survivors. One- and three-yr RHCs confirmed stable PH reversal (n = 26, all three-yr survivors). Parameters of late RV function and remodeling proved satisfactory. Parameters of functional capacity (Vo2 peak 19.7 ± 3.6 mL/kg/min and slope VE/Vco2 34.8 ± 2.7) proved homogeneous to those measured in transplant recipients with normal preoperative pulmonary artery pressure. Oral sildenafil is effective in allowing candidacy, safe transplantation, and long-term survival in PH recipients initially disqualified.

Background: Extracellular matrix (ECM) participates in heart growth and influences cardiac stem-cell differentiation and migration. The modification of ECM associated with cardiomyopathies is a complex process involving a cohort of proteins. ECM proteins are involved in the regulation of neoangiogenesis in physiological and pathological conditions through their interaction with some angiogenic factors. Our aim was to investigate the role of some angiogenesis-related ECM proteins in the remodeling heart. Methods: We examined cardiac tissue samples from 21 explanted human hearts and 10 non-failing hearts before transplantation. Each specimen was submitted to morphological and biomolecular analysis. Results: We demonstrated a reduced expression of α2-chain laminin mRNA in pathological samples that could play an important role in the progression of cardiac failure by contributing to sarcolemma modifications. Reduced expression of tenascin cytotactin (TN-C) and TN-X in explanted hearts indicated chronic cardiac damage and an impaired capacity to stimulate new vessel development. The observed type IV collagen increase was not related to neoangiogenesis, as reflected by the decreased expression of vascular endothelial growth factor (VEGF)-A and VEGF receptor-2. The inverse correlation between heart dimension and VEGF-A immunopositivity seems particularly interesting. Conclusions: Our findings suggest that ECM reacts strongly to ischemic damage in failing hearts through some important modifications of its protein composition. Nevertheless, this reaction cannot completely restore myocardium structure if it is not supported by adequate neoangiogenesis. The decrease in some ECM proteins related to vessel development has a negative effect on postischemic neoangiogenesis and clinical outcome.

Since the early days of cardiac surgery, postoperative pulmonary dysfunction has been the subject of a considerable amount of experimental and clinical research because it affects virtually every treated patient [1]. Both anomalies in gas exchange and lung mechanics contribute to the expression of postoperative respiratory dysfunction, which is clinically evidenced by increased work of breathing and respiratory rate, shallow respirations, ineffective cough, hypoxemia, and changes in chest radiographs. Widening of the alveolar-arterial oxygen gradient, increased lung microvascular permeability, and increased pulmonary vascular resistance and shunt fraction are commonly observed after cardiac surgical procedures. Accordingly, reductions in vital capacity, functional residual capacity, and static as well as dynamic lung compliance are usually evident. Pathogenesis of these derangements has been extensively studied [2, 3]. It stems from a complex interplay between patients’ baseline end organ function; the type, extent, and urgency of underlying cardiovascular pathology; and the distinct features of this surgical setting. This operative approach encompasses general anesthesia, peculiar surgical trauma (median sternotomy, pleural dissection), cardiopulmonary bypass, topical cooling for myocardial protection (which may cause phrenic nerve dysfunction), transfusion of blood products, and postoperative pain, which individually and synergistically affect respiratory performance.

Early graft failure (EGF) is a dreaded complication after heart transplantation (HT). Despite several improvements, no effective therapy has been developed and the prognosis is poor. We evaluated the risk factors and clinical impact of EGF. In a consecutive series of 317 HTs performed at a single institution between January 1999 and December 2008, variables associated significantly with EGF were sought in bivariate and multivariable discriminant analyses. The deriving propensity score was used to stratify the study sample in to three groups (low, intermediate and high risk for EGF). Comparisons were performed between the higher-risk group and the remaining population in terms of preoperative features and outcomes. EGF occurred in 10.1% of the overall population (2.9, 3.8 and 23.6%, respectively, in the three groups). Overall, EGF-related mortality was 56.3% (100, 75 and 48%, respectively, in the three groups). Determinants of EGF in the highest-risk group were: redo procedure, valvular cardiomyopathy, status one at transplant, recipient male sex, donor–recipient (D/R) weight mismatch, high inotropic donor support, ischaemic time and first day troponin I release. In conclusion, several donor and recipient features predicted EGF. Since such characteristics are not readily modifiable but synergistically determine the occurrence of EGF, optimization of D/R matching is crucial to prevent it.

Objectives This pilot prospective observational study aimed to evaluate the maternal and fetal outcomes of pregnancies under low-dose oral anticoagulation therapy after aortic mechanical replacement. Background Need for valve replacement is still an issue for young women with native valve disease who are planning on future pregnancy. Choice of replacement device is a challenging clinical task. Methods A comprehensive pre-operative counseling protocol to guide choice of replacement device was developed. The pre-operative anticoagulation trial to determine the warfarin daily dosage needed to reach target international normalized ratio (INR) represented the main stem of such protocol. Pregnancies on low-dose anticoagulation therapy (target INR: 1.5 to 2.5) were allowed in a highly selected subset of mechanical aortic valve recipients. Results Twenty-two patients of 40 originally referred for native valve disease surgery requiring valve replacement, safely underwent the pre-operative anticoagulation challenge. No maternal or fetal complications were detected in 16 pregnancies under low oral anticoagulation. Patterns of warfarin daily dosage and induced INRs were characterized during pregnancy. Conclusions In this small sample observational study, a pre-operative anticoagulation therapy trial helped young women scheduled for valve replacement to acquire complete information as to the choice of prosthetic device. In selected third-generation mechanical aortic prosthesis recipients, low-dose anticoagulation therapy seems safe and feasible for both mother and fetus. Further studies are needed to validate this approach.

Backgrou nd Moderate anticoagulation after mechanical heart valve replacement has been proposed to reduce the risk of bleeding related to lifelong anticoagulation. However, the efficacy of such reduced antithrombotic regimens is still unknown. The present prospective open-label, single-center, randomized controlled trial aimed to evaluate the safety and feasibility of reduced oral anticoagulation after isolated mechanical aortic valve replacement. Metho ds Low-risk patients undergoing bileaflet mechanical aortic valve replacement were randomized to a low International normalized ratio (INR) target (1.5-2.5; LOW-INR group) or to the standard currently recommended INR (2.0-3.0; CONVENTIONAL-INR group) through daily coumarine oral therapy. No aspirin was added. Median follow-up was 5.6 years. Th e pr imar y out co me was a sse ss me nt of no ni nfe ri ori ty of t he lo w ov er the s tan dar d an t ico agu l ati on reg imen on thromboembolic events. Secondary end point was the superiority of the reduced INR target strategy on bleeding events. Results We analyzed 396 patients (197 in the LOW-INR group and 199 in the CONVENTIONAL-INR group). The mean of INR was 1.94 ± 0.21 and 2.61 ± 0.25 in the LOW-INR and CONVENTIONAL-INR groups, respectively (P b .001). One versus three thromboembolic events occurred in the LOW-INR and CONVENTIONAL-INR, respectively, meeting the noninferiority criterion ( P = .62). Total hemorrhagic events occurred in 6 patients in the LOW-INR group and in 16 patients in the CONVENTIONAL-INR group (P = .04). Conclusio ns LOWERING-IT trial established that the proposed LOW-INR target is safe and feasible in low-risk patients after bileaflet aortic mechanical valve replacement. It results in similar thrombotic events and in a significant reduction of bleeding occurrence when compared to the conventional anticoagulation regimen.

Background: Obesity, dyslipidemia, hypertension, and diabetes mellitus are common features after heart transplantation and they lead to coronary artery disease and graft loss. Aim: To determine the effects of a dietary intervention on nutritional status and metabolic outcome of two groups enrolled during or after the first year from the transplant. Methods: Forty two subjects (mean age 51.36±12.4 yr) were studied; 20 were enrolled during the first year by the transplant, 22 were enrolled after the first year from the transplant (7.9±3.86 and 56.86±38.6 months after surgery, respectively). According to diet compliance both groups were divided into two subgroups and they were prospectively followed for 4 years. Anthropometric measurements, biochemical nutritional markers, and dietary records were collected at baseline (T0) and after a 12-month follow-up period (T12) and a 48-month follow-up period (T48). Body composition was performed at T0 and T12. Results: Diet compliance was associated with a decrease in total cholesterol, triglycerides and glucose plasma level and with a weight loss mainly due to a decrease in fat mass. Conclusion: Our study shows the efficacy of dietary intervention to obtain an early and late weight and metabolic control after heart transplant.

Background Evaluation of the impact of prosthesis-patient mismatch (PPM) on long-term outcome and quality of life (QOL) in elderly patients who underwent implantation of small size bileaflet prostheses for aortic stenosis. Methods Between September 1988 and September 2006, 377 patients aged greater than 70 years underwent aortic valve replacement with a small size bileaflet prosthesis (17, 19, and 21 mm) in one Institution. The study population's survivors (345 patients) were divided into three groups according to the indexed effective orifice area (EOAI): Group A included patients with EOAI less than 0.60 cm 2 /m 2 ; group B included patients with EOAI ranging between 0.61 and 0.84 cm 2 /m 2 ; and group C included patients with EOAI 0.85 cm 2 /m 2 or greater. Cumulative and comparative analyses of long-term outcomes and of left ventricular mass regression were performed. The QOL was evaluated with the 36-Item Short Form Health Survey (SF-36) questionnaire. Results Overall hospital mortality was 8.5% (32 patients). Group A included 33 patients (9.6%), group B 175 (50.7%), and group C 137 (39.7%). Actuarial survival was 88.8% ± 0.016 at 1 year, 82.1% ± 0.022 at 5 years, and 76.7% ± 0.032 at 10 years. No difference emerged among the three groups. A significant reduction in left ventricular mass was observed in all groups and in all patient subsets of prosthetic size. The scores obtained in the SF-36 test were similar in the three groups and significantly higher than those of the general population ( p Conclusions Incidence of severe PPM is low after aortic valve replacement. Presence of severe or moderate PPM, did not influence long-term outcome, left ventricular mass regression and QOL in a population of septuagenarians.

Objectives Peak oxygen uptake (Vo 2 ) and ventilatory efficiency have prognostic implications in the population with congestive heart failure. This study evaluated quality-of-life functional capacity after the 2 treatment strategies of surgical ventricular restoration and transplantation for severe left ventricular dysfunction of ischemic cause. Methods The 75-patient study population (between 2004 and 2006) with severe heart failure included 35 patients undergoing surgical ventricular restoration (mean age, 62.6 ± 8.7 years), sometimes together with coronary artery bypass grafting or mitral surgery, and 40 cardiac transplant recipients (mean age, 55.6 ± 7.7 years). Preoperative and 6-month postoperative function (peak Vo 2 , the anaerobic threshold, and the slope of minute ventilation/carbon dioxide uptake), cardiac catheterization parameters (left and right), and hospital and early outcomes were evaluated. Results The 2 groups had comparable baseline functional impairment and experienced similar hospital stay and early outcomes. They also showed similar improvements in left ventricular volume indexes and hemodynamic parameters and sustained significant improvements of median Vo 2 , anaerobic threshold, and minute ventilation/carbon dioxide uptake values. Conclusions Both surgical strategies resulted in a significant and comparable improvement of functional capacity at the 6-month evaluation. These early studies must be repeated to determine the long-term benefits of surgical ventricular restoration because maximal Vo 2 and ventilatory efficiency lose their prognostic survival role after transplantation.

The aim of this study was to determine whether changes in prognosis and quality of life (QOL) after aortic valve replacement (AVR) in octogenarians differ depending on the choice of mechanical (MP) or tissue (BP) valves.Between July 1992 and September 2006, 160 consecutive octogenarians underwent AVR with (18.8%) or without concomitant coronary artery bypass grafting. At follow-up (mean 3.4 +/- 2.8 years, 552 patient-years, 98.3% complete), 121 were still alive and answered the Medical Outcomes Study Short-Form 36 Health Survey (SF-36) QOL questionnaire.Group BP had 62 patients. Group MP had 98 patients. Preoperative risk factors were comparable except group BP was older. Global hospital mortality was 8.8%. There were 21 late deaths, 61.9% of which were not valve- or anticoagulation-related. A significant difference emerged in 1-, 3-, 5- and 8-year actuarial survival rates (BP: 86.4% +/- 0.04%, 76.9% +/- 0.06%, 58.1% +/- 0.1%, 46.5% +/- 0.14%, respectively, vs MP: 91.3% +/- 0.03%, 88.6% +/- 0.03%, 81.6% +/- 0.05%, 70% +/- 0.67%; p = 0.025) but not in terms of 8-year freedom from valve-related complications (82.6% +/- 0.1% vs 87% +/- 0.053%, p = 0.55). One anticoagulant-related hemorrhage occurred in group MP; one stroke occurred in group BP. Survivors had significant improvement in New York Heart Association functional class compared with preoperatively (1.1 vs 2.8, p0.001) Mean QOL scores were satisfactory and substantially comparable between the two groups; in seven domains, scores were higher than those of the age- and sex-matched general Italian population.Long-term survival after AVR in selected octogenarians was similar to that of the general elderly population. The device type exerted no influence on QOL.

Postischemic cardiomyopathy remains one of the disorders in urgent need of effective noninvasive therapy. It is currently accepted that the isolation, expansion and application of resident cardiac stem cells may hold therapeutic promise for the future. Recently, it has been demonstrated that shock waves (SW) could enhance the expression of vascular endothelial growth factor (VEGF) and its receptor, Flt-1. As the development of angiogenic noninvasive therapy is very important for future therapeutic strategies in cardiovascular diseases, we examined in vitro, the effects of SW treatment on adult resident cardiac primitive cells isolated from bioptic fragments of normal human hearts and from explanted pathologic hearts with postischemic cardiomyopathy. This study demonstrates that SW have positive influence on both the proliferation and the differentiation of cardiomyocytes, smooth muscle and endothelial cells precursors, with a more obvious effect being evident in the cells from normal heart than in those taken from pathologic hearts. Our results suggest that SW treatment could inhibit or retard the pathologic remodeling and functional degradation of the heart if applied during the early stages of heart failure.

Perioperative transfusions are known to increase morbidity and mortality after coronary artery bypass grafting (CABG). The aims of the study were (1) to identify the clinical profile of the patient subset at highest risk from transfusion and (2) to disclose causative relationship and dose-dependency of transfusion on hospital mortality.A prospective observational design was employed on a cohort of 1047 consecutive patients (median age 63.2 ± 9.3, 18.8% female, 30.6% diabetics, 31.9% urgent/emergent, 15.3% with low preoperative left ventricular ejection fraction (LVEF)) who underwent on-pump isolated CABG between January 2004 and December 2007. Univariate and multivariate regression analysis and post-hoc risk stratification, by means of propensity scoring and binary segmentation, were adopted.The following independent risk factors were identified: age, body surface area (BSA), preoperative glomerular filtration rate, preoperative haemoglobin, surgical priority, length of cardiopulmonary bypass, intraoperative haemodilution and early postoperative blood loss. The patient population was stratified in quintiles of transfusional risk, by means of propensity scoring. As to modifiable risk factors, patients in the highest quintiles of risk were those with BSA (1.73, preoperative haemoglobin12 g/dl, intraoperative haemoglobin8.0 g/dl and those undergoing cardiopulmonary bypass90'). Binary segmentation was performed to avoid any association between red cell transfusion and worse outcomes being causative and dose-dependent. A dose-dependent pattern was disclosed, with patients receiving5 units being at highest risk.High exposure to blood transfusions may be prevented by preoperative patient stratification and by the close tailoring of management strategies on planning and implementing surgical timing, as well as by cardiopulmonary bypass technique.

Objective: To review outcomes and quality of life following two surgical strategies for severe left ventricular dysfunction due to ischemic dilated cardiomyopathy. Methods: Hospital and follow-up records of 111 patients with extensive ischemic cardiomyopathy (mean age 57.3G 8.4) referring to our institution between January 1996 and December 2003 were reviewed. Group A included 42 patients (mean age 62.4G7.9) with morphological and functional cardiac parameters allowing for ventricular restoration (including endoventricular circular patch plasty, coronary artery by-pass grafting, and, when needed, mitral surgery). Group B included 69 patients (mean age 54.3G7.2), undergoing cardiac transplantation. Hospital mortality, treatment-related late mortality, incidence of cardiac events, freedom from cardiac failure, freedom from hospital re-admission, functional recovery at follow-up (3075.2 pts/months; 100% complete) and quality of life (WHOQOL test) were assessed. Results: Hospital mortality was 19% in group A and 8.7% in group B (PZ0.143). No treatment-related late deaths were observed in group A, while six deaths (9.5%) occurred in group B (PZ0.063). Incidence of cardiac events was comparable. At 60 months, freedom from cardiac failure was 93.5G0.04 and 86.2G0.05%, respectively (PZ0.23), freedom from hospital re-admission was 93.5G0.04 and 61.3G0.07% (PZ0.002). Exertion dyspnea was present in 40% patients in group A versus 13% in group B (PZ0.006). WHOQOL test showed a satisfying quality of life in both groups, although patients undergoing restoration reached higher scores in the psychological and social domains. Conclusions: Selected patients with ischemic cardiomyopathy, potentially eligible for transplantation, can be managed by ventricular restoration. In those patients post-operative quality of life is satisfactory, with comparable survival and low risk of re-hospitalization. q 2004 Elsevier B.V. All rights reserved.

Background Although surgical management with early debridement and closed mediastinal irrigation has proved successful in reducing early mortality following poststernotomy deep sternal wound infection, recurrence rates are still up to 20%. This study compared the effectiveness and safety of wound dressing with granulated sugar versus early muscle flap surgery in the management of recurrent postoperative Staphylococcal mediastinitis. Methods Between January 1995 and January 2002, 25 patients with severe recurrent staphylococcal mediastinitis were treated with granulated sugar wound dressing (group A) or with wound debridement, v-shape sternectomy and associated muscle flap surgery (group B). Clinical outcomes and perioperative data were analyzed. Outcomes were compared between the groups evaluating the length of time for normalization of white blood cell (WBC) count and of body temperature and length of hospital stay. Patient characteristics determining best treatment option were identified. Survival and incidence of recurrence at follow-up were also analyzed. Results Study groups proved homogenous as to preoperative characteristics. Complete cure was achieved earlier in group A than in group B (defervescence: p = 0.0005; WBC normalization: p = 0.0001, respectively). Hospital stay was shorter in group A. A statistically significant difference was found in hospital mortality (16% overall) between the two groups with better outcomes in group A ( p = 0.039). In the patient subset with the most severe preoperative profile (hemodialysis, tracheostomy, inotropic support) surgical treatment produced worse results than the sugar dressing method ( p = 0.048). No case of recurrence was observed. Conclusions Both treatments proved effective in recurrent type IV A Staphylococcal mediastinitis. Granulated sugar proved a safer option in severely compromised patients.

OBJECTIVE: To assess the determinants of pregnancy outcome in patients with mechanical valve prostheses anticoagulated with warfarin. METHODS: Between January 1987 and January 2000, 52 patients with mechanical valve prostheses who had 71 pregnancies were anticoagulated with warfarin for the entire duration of pregnancy. Warfarin was withdrawn 48 hours before and 24 hours after a scheduled cesarean delivery carried out by the end of the 37th gestational week. The targeted international normalized ratio ranged between 2.25 and 4.0, depending on the prosthetic model. Exact univariate and multivariable analyses were performed to assess which among the following variables predicted poor pregnancy outcome: patient age, prosthetic model, site of implantation, average international normalized ratio, and average daily dose of warfarin. RESULTS: Pregnancy loss occurred in 23 of 71 of pregnancies, stillbirth in five of 71, embryopathy in four of 71 (two aborted fetuses and two full-term infants). There were no maternal deaths or thromboembolic or hemorrhagic complications. Warfarin daily dosage over 5 mg per day was a significant predictor of poor pregnancy outcome (P CONCLUSION: The risk for pregnancy complications in patients treated with sodium warfarin is higher when the mean daily dose exceeds 5 mg.

OBJECTIVESThe purpose of this study was to assess the incidence of warfarin fetal complications and whether they are dose-dependent.BACKGROUNDGravid patients with mechanical heart valves require long-term anticoagulant therapy. Controversy exists concerning the appropriate treatment of these patients.METHODSForty-three women on warfarin carrying out 58 pregnancies were studied. For each patient with full-term pregnancy a caesarian section was scheduled for the 38th week during brief warfarin discontinuation. Maternal and fetal complications were evaluated. Fetal complications were divided according to the warfarin dosage ≤5 mg and >5 mg necessary to keep an international normalized ratio (INR) of 2.5 to 3.5, and analyzed subsequently.RESULTSA total of 58 pregnancies were observed: 31 healthy babies (30 full term, 1 premature) and 27 fetal complications (22 spontaneous abortions, 2 warfarin embryopathies, 1 stillbirth, 1 ventricular septal defect, 1 growth retardation) were recorded. Two maternal valve thromboses occurred. No fetal or maternal bleeding was observed during caesarian sections or premature vaginal delivery. Patients whose warfarin doses during pregnancy were >5 mg had 22 fetal complications, whereas those taking a dose ≤5 mg had only five fetal complications (p = 0.0001). For an increase of the warfarin dose there was a substantially increased probability of fetal complications (p < 0.0001; ρ < 0.7316).CONCLUSIONSThere is a close dependency between warfarin dosage and fetal complications. Patients on warfarin anticoagulation may be delivered by planned caesarian section at the 38th week while briefly interrupting anticoagulation.

In 1992, the defmition of erectile dysfunction (ED) replaced the old term of impotence that had been used for many centuries, in order to avoid the general confusion existing until today in this field. In the past, the origin of impotence had been attributed to different causes such as psychological diseases, or witches and demons. In 1764, Fusanacci described impotence that can occur in the male as well as in the female, as a defect in reproduction. The main causes responsible for impotence were identified as inability to achieve erection, a very fluid seminal ejaculation, a defective organ, dryness of testicles, and lack of copulative power after many sexual intercourses with healthy women. Some decades later in 1847, Beatty affirmed that one of the most remarkable changes that can be observed in the passage from childhood to maturity is the development of the sexual organs, followed by the appearanee of new sensations. He dis1inguished impotenee that oeeurs only in men from sterility that for him affeets women, and divided the eauses of impotenee into 3 classes: organie, functional and moral (today defmed as psyehologieal). For Beatty, the . progress of knowledge had taken away magie and soreery from the human mind and now it was widespread only ," among the lowest and most ignorant classes of humble people. In this way, he shows the evolution ofmedieal scienee d~ in XIX eentury in aceepting only the rational explanation of the human diseases.

Previous studies on BAV (bicuspid aortic valve)-related aortopathy, whose aetiology is still debated, have focused mainly on severe dilatations. In the present study, we aimed to detect earlier signs of aortopathy. Specimens were collected from the ‘concavity’ (lesser curvature) and the ‘convexity’ (greater curvature) of mildly dilated AAs (ascending aortas; diameter ≤4 cm) with stenotic TAV (tricuspid aortic valve) or BAV and from donor normal aortas. Specimens were submitted to morphometry, immunohistochemistry and differential gene-expression analysis, focusing on SMC (smooth muscle cell) phenotype, remodelling, MF (myofibroblast) differentiation and TGFβ (transforming growth factor β) pathway. Smoothelin and myocardin mRNAs decreased in all the samples from patients, with the exception of those from BAV convexity, where a change in orientation of smoothelin-positive SMCs and an increase of α-SMA (α-smooth muscle actin) mRNA occurred. Dilated aortas from BAV and TAV patients showed both shared and distinct alterations concerning the TGFβ pathway, including an increased TGFβ and TGFβR2 (TGFβ receptor 2) expression in both groups and a decreased TGFβR1 expression in BAV samples only. Despite a decrease of the mRNA coding for the ED-A (extra domain-A) isoform of FN (fibronectin) in the BAV convexity, the onset of the expression of the corresponding protein in the media was observed in dilated aortas, whereas the normal media from donors was negative for this isoform. This discrepancy could be related to modifications in the intima, normally expressing ED-A FN and showing an altered structure in mild aortic dilatations in comparison with donor aorta. Our results suggest that changes in SMC phenotype and, likely, MF differentiation, occur early in the aortopathy associated with valve stenosis. The defective expression of TGFβR1 in BAV might be a constitutive feature, while other changes we reported could be influenced by haemodynamics.

The need for a specific risk score system for infective endocarditis (IE) surgery has been previously claimed. In a single-center pilot study, preliminary to future multicentric development and validation, bivariate and multivariate (logistic regression) analysis of early postoperative mortality predictors in 440 native valve IE patients were performed. Mathematical procedures assigned scores to the independent predictors emerged (AUC of the ROC curve: 0.88). Overall mortality was 9.1%. Six predictors were identified and assigned scores, including age (5–13 points), renal failure (5), NYHA class IV (9), critical preoperative state (11), lack of preoperative attainment of blood culture negativity (5), perivalvular involvement (5). Four risk classes were drawn ranging from “very low risk” (≤5 points, mean predicted mortality 1%), and to “very high risk” (≥20 points, 43% mortality). IE-specific risk stratification models are both needed, as disease-specific factors (e.g., cultures, abscess), beside the generic ones (e.g., age, renal impairment) affect mortality, and feasible.

We read with appreciation the article by Leone et al. [1], reporting absent correlation between aortic diameter and degree of medial degeneration (MD) in a surgical cohort of bicuspid aortic valve (BAV) patients. Thirty-eight per cent of patients with aortic diameter ≤4.5 cm had moderate or severe histological alterations, and this highlighted the limitations of the dimensional criterion currently adopted to risk-stratify BAV aortopathy patients. However, the authors failed to comment on another equally important finding: absent/mild MD was found in >60% patients undergoing ascending aorta replacement, according to official guidelines or intraoperative macroscopic appearance of the aortic wall [1]. Before considering the consequences of this finding, methodological issues should be ruled out: first, the site of sample retrieval might have been a confounding factor. BAV aortopathy can assume different anatomo-clinical phenotypes, each likely subtended by distinct pathogenesis: in an outpatient setting, we distinguished 14% BAV patients (young men, aortic regurgitation) with ‘root-dilatation phenotype’ (enlargement of the sinuses of Valsalva) from another 70% (older age, women, BAV stenosis) with supracoronary dilatation [2]. In a purely surgical series, frequencies can be different; moreover, even in case of initial root localization the disease can extend to the more distal tracts, including the arch, as it progresses, adding to phenotypic variability [3]. How many patients in Leone’s study had a root-dilatation phenotype? The authors stated that six samples were obtained from different sites [1]: did these encompass sinuses and the ascending tract in all patients? Was MD grading performed only in the specimens from the level of maximal diameter? Otherwise, if the reported grades were averaged among the six sites (which would explain the absence of grade 4 cases), the results might be biased. Although we agree with the choice of excluding atherosclerotic changes from the grading criteria, atherosclerotic lesions should have been separately accounted for, as they could subtend some dilatations showing absent/mild MD: notably, the prevalence of low grades increased with age [1]. Moreover, by using histology alone, without histochemical and biomolecular insights, more subtle cell alterations and extracellular matrix changes might have been overlooked. In our ongoing research on BAV aortas with mean diameter as small as 3.9 cm, gene expression analysis is revealing significant alterations in resident cell phenotype and transforming growth factor-beta signalling (unpublished data). Most likely, the authors’ results were only in part affected by the above flaws, and therefore they deserve serious consideration, as the alarming evidence is presented that we are currently unable to non-invasively detect aortopathy without dilatation, but also we currently replace, according to guidelines, a number of aortas with absent/mild histological alterations! Are those aortas really at risk of dissection or fast growth? Words of caution were recently issued about the current aggressiveness in prophylactic aorta replacement for BAV disease [3, 4]. The paper by Leone et al. [1], as well as our most recent research [5], underscores the need for further investigation on the pre-surgical stages of BAV aortopathy, to identify early predictors of aortic dilatation/dissection, including functional (rather than merely dimensional) imaging measurements [5] and humoral biomarkers [6].

OBJECTIVES: Unresponsive pulmonary hypertension (PH) may contraindicate heart transplant since it implies poor early outcomes. The present study reports the effectiveness of oral perioperative sildenafil in allowing heart transplant candidacy and surgery in a selected group of patients initially deemed ineligible because of PH. METHODS: Between May 2005 and December 2009, 31 consecutive patients (5 females, 9 with a history of idiopatic cardiomyopathy and 16 with a history of coronary artery disease, 10 with previous sternotomies, 71.42 ± 27.69 ml/min/m 2 mean pre-operative epidermal growth factor receptor) were qualified for oral sildenafil because of unresponsive PH at baseline right heart catheterization (RHC). After a 12-week trial, RHC disclosed PH reversibility (mean pulmonary vascular resistance index: 9.57 ± 4.07 WU, mean transpulmonary gradient 14.47 ± 5.66 mmHg and mean systolic pulmonary artery pressure: 68.96 ± 15.15 mmHg), allowing listing despite a higher risk for early post-transplant RV failure. Transplant protocol included donor/recipient size matching ≥0.8 and inhaled nitric oxide in the early post-operative period followed by reinstitution of oral sildenafil. RESULTS: All patients underwent heart transplantation. Mean overall graft ischaemic time was 179 ± 47min; mean donor recipient weight ratio was 1.04 ± 0.17. Right ventricular failure developed in three patients (9.6%) and hospital mortality was 3.2%. Protocol RHC disclosed pulmonary haemodynamic profile normalization within the third post-operative month allowing weaning from sildenafi li n the 30 hospital survivors. One-year RHC confirmed PH reversal (n= 29 patients, all who survived up to 1year). CONCLUSIONS: This pilot prospective uncontrolled trial suggests that oral sildenafil is effective in allowing candidacy, safe transplantation and post-operative pulmonary profile normalization in potential recipients initially disqualified because of PH.

Background: Papillary fibroelastomas (PFEs) are rare cardiac tumors usually treated by shave resection. Up to 20% of the patients are actually denied such a conservative surgical approach because atypical morphology is thought to preclude radical and effective outcomes.Methods/Results: Surgical tricks and tips of shave resection are elucidated, and a case series presentation of the morphology of atypical PFEs treated by shave resection is described.Conclusion: In experienced hands surgical shave resection is the gold standard for the treatment of PFE even in atypical presentations.

Objective: Data regarding risks and consequences of acute kidney injury (AKI) after cardiac transplantation are dismissingly few and unclear. This study defined the incidence, risk factors and prognostic implication of AKI in a single-center cohort operated on between January 1999 and December 2008. Methods: Data from 307 consecutive recipients (mean age: 47.42 13.58, 20.5% female, 18.9% diabetics, 19.5% with previous cardiac operations, 26.4% hospitalized, 78.4 33.7 ml min 1 preoperative glomerular filtration rate (eGFR)) were analyzed using multivariable logistic regression modeling. AKI was defined according to RIFLE (Risk, Injury, and Failure; and Loss, and End-stage kidney disease) criteria. Results: RIFLE scores of I or F were detected in 14%, and continuous venovenous hemofiltration was needed in 6.1%. Risk factors for AKI were: previous cardiac operation (odds ratio (OR) 2.35; 95% confidence interval (CI), 1.11—4.9), blood transfusion (OR 1.08; 95% CI, 1.011—1.16), troponin I release >10 (OR 1.031; 95% CI, 1.001—1.064), length of ischemic time (OR 1.008; 95% CI, 1.011—1.16). Overall hospital mortality averaged 7.8% and overall 1-year mortality was 10.4%; both mortality rates increased with each RIFLE stratification (Normal 3.4%, RIFLE R = 7.1%; RIFLE I = 25.7%; and RIFLE F = 37.5% and Normal 5.6%, RIFLE R = 11.8%, RIFLE I = 25.7%, and RIFLE F = 37.5%, respectively). AKI proved independent predictors of both early and 1-year mortality. The burden of AKI significantly affected 1-year kidney function (D preoperative GFR 1-year GFR in AKI vs no AKI = 25.872 22.54 vs 7.968 34.18, p = 0.015). Conclusions: AKI is a highly prevalent and prognostically important complication. Some of the risk factors for AKI identified may be modifiable. # 2011 European Association for Cardio-Thoracic Surgery. Published by Elsevier B.V. All rights reserved.