Regional mapping of myocardial hibernation phenotype in idiopathic end-stage dilated cardiomyopathy.

Myocardial hibernation (MH) is a well-known feature of human ischaemic cardiomyopathy (ICM), whereas its presence in human idiopathic dilated cardiomyopathy (DCM) is still controversial. We investigated the histological and molecular features of MH in left ventricle (LV) regions of failing DCM or ICM hearts. We examined failing hearts from DCM (n = 11; 41.9 ± 5.45 years; left ventricle-ejection fraction (LV-EF), 18 ± 3.16%) and ICM patients (n = 12; 58.08 ± 1.7 years; LVEF, 21.5 ± 6.08%) undergoing cardiac transplantation, and normal donor hearts (N, n = 8). LV inter-ventricular septum (IVS) and antero-lateral free wall (FW) were transmurally (i.e. sub-epicardial, mesocardial and sub-endocardial layers) analysed. LV glycogen content was shown to be increased in both DCM and ICM as compared with N hearts (P < 0.001), with a U-shaped transmural distribution (lower values in mesocardium). Capillary density was homogenously reduced in both DCM and ICM as compared with N (P < 0.05 versus N), with a lower decrease independent of the extent of fibrosis in sub-endocardial and sub-epicardial layers of DCM as compared with ICM. HIF1-α and nestin, recognized ischaemic molecular hallmarks, were similarly expressed in DCM-LV and ICM-LV myocardium. The proteomic profile was overlapping by ~50% in DCM and ICM groups. Morphological and molecular features of MH were detected in end-stage ICM as well as in end-stage DCM LV, despite epicardial coronary artery patency and lower fibrosis in DCM hearts. Unravelling the presence of MH in the absence of coronary stenosis may be helpful to design a novel approach in the clinical management of DCM.

Prognostic role of myocardial performance index on long-term survival after heart transplantation: a prospective study.

The survival rate of heart transplant patients is increasing, underlying the need for accurate predictors of adverse events during clinical follow-up. Myocardial performance index (MPI) is a Doppler-derived index of combined systolic and diastolic function: we assessed the prognostic role of MPI in survival of patients >1 year after heart transplantation (HT). A total of 152 consecutive HT patients referred to our institution were enrolled in this prospective study. Primary endpoints were cardiac death and a composite of major adverse cardiac events (MACE). During follow-up (69 ± 22 months), 68 (44.7%) patients had an adverse event and 20 (13.15%) patients died. Patients with MACE during follow-up showed lower EF (57.3 ± 9.3 vs. 63 ± 6.1; P < 0.001) and higher MPI (0.45 ± 0.19 vs. 0.31 ± 0.13; P < 0.001) at enrolment. MPI and EF were independently related to MACE (OR = 2.2; 95% confidence interval [CI] = 1.01-5.1; and OR = 6.6; 95% CI = 3.5-11.2, respectively) and showed strong diagnostic power (MPI: receiver operating characteristic [ROC] area = 79%, with 79% sensitivity and 81% specificity; EF: ROC area = 77%, with 54% sensitivity and 91% specificity) in the subsequent year. Patients with EF > 50% and MPI < 0.45 at enrolment showed 75% event-free survival 5 years after HT. In HT patients, MPI combined with EF was an accurate means of predicting long-term adverse events.

Human cardiac progenitor cell grafts as unrestricted source of supernumerary cardiac cells in healthy murine hearts.

Human heart harbors a population of resident progenitor cells that can be isolated by stem cell antigen-1 antibody and expanded in culture. These cells can differentiate into cardiomyocytes in vitro and contribute to cardiac regeneration in vivo. However, when directly injected as single cell suspension, less than 1%-5% survive and differentiate. Among the major causes of this failure are the distressing protocols used to culture in vitro and implant progenitor cells into damaged hearts. Human cardiac progenitors obtained from the auricles of patients were cultured as scaffoldless engineered tissues fabricated using temperature-responsive surfaces. In the engineered tissue, progenitor cells established proper three-dimensional intercellular relationships and were embedded in self-produced extracellular matrix preserving their phenotype and multipotency in the absence of significant apoptosis. After engineered tissues were leant on visceral pericardium, a number of cells migrated into the murine myocardium and in the vascular walls, where they integrated in the respective textures. The study demonstrates the suitability of such an approach to deliver stem cells to the myocardium. Interestingly, the successful delivery of cells in murine healthy hearts suggests that myocardium displays a continued cell cupidity that is strictly regulated by the limited release of progenitor cells by the adopted source. When an unregulated cell source is added to the system, cells are delivered to the myocardium. The exploitation of this novel concept may pave the way to the setup of new protocols in cardiac cell therapy.

Nickel allergy, how deep?

A 41-year-old woman was referred to our Cardiology Unit to evaluate the feasibility of a percutaneous closure of her 20-mm atrial septal defect. During the last few months she had increasing dyspnoea, and an echocardiographic study had disclosed an atrial septal defect with significant right ventricular enlargement. Her past medical history was silent, except for Nickel (Ni2+) allergy confirmed by a skin patch test. Ni2+ allergy is a problematic issue in patients scheduled for Ni(2+)-containing devices. The atrial septal occluder device that we used consists of a metallic alloy composed of 55% nickel and 45% titanium. Starting from the aforementioned case we reviewed all available literature and illustrated our final resolution.

Relationship between ventricular pressure and coronary artery disease in asymptomatic adult heart transplant recipients.

INTRODUCTION: The association between data of right heart catheterization and cardiac allograft vasculopathy (CAV) in adult heart transplant (HTx) recipients remains to be determined. METHODS AND RESULTS: This is an observational, retrospective study, including all consecutive asymptomatic HTx patients undergoing routine right and left catheterization. The independent predictive power of pulmonary capillary wedge pressure (PCWP) to predict CAV (classified according to working formulation of a standardized nomenclature for CAV-2010) was the primary end point. Seventy-one patients were included, with a mean time from HTx to procedure of 19 ±â€Š25 months. At coronary angiography first degree of CAV was found in eight patients (11.2%), second degree of CAV in two patients (2.8%), and third in two (2.8%). PCWP values were significantly higher in patients with CAV compared with patients without CAV (17.5 ±â€Š7.5 vs. 10.4 ±â€Š5.6, P < 0.001) and values of 15 mmHg or greater had an AUC of 0.71 (0.48-0.92), with a sensitivity of 71% and a specificity of 73% in predicting CAV, with an independent relationship confirmed at logistic regression analysis (odds ratio 1.28, IC 1.06-1.53; P = 0.008). CONCLUSION: A significantly elevated PCWP at the time of the diagnosis of transplant coronary artery disease may be considered as an early marker of CAV, especially in asymptomatic HTx recipients.

Incidence and severity of primary graft dysfunction after lung transplantation using rejected grafts reconditioned with ex vivo lung perfusion.

OBJECTIVES: Ex vivo lung perfusion (EVLP) is a novel technique used to evaluate and recondition marginal or rejected grafts. Primary graft dysfunction (PGD) is a major early complication after lung transplantation (LTx). The use of marginal or initially rejected grafts may increase its incidence and severity. The aim of this study is to evaluate the incidence of PGD after LTx using rejected grafts reconditioned with EVLP. METHODS: PGD has been evaluated immediately after LTx (t0) and after 72 h (t72) in patients receiving standard (Group A) or reconditioned (Group B) grafts. EVLP was performed using a controlled acellular perfusion according to the Toronto technique. RESULTS: From July 2011 to February 2013, 36 LTxs have been performed: 28 patients (21 M/7 F, mean age 51.7 ± 14.7 years) in Group A and 8 (6 M/2 F, mean age 46.6 ± 9.8 years) in Group B (successful recondition rate of 73%, 8 of 11 cases). Incidence rate of PGD 3 at t0 and at t72 (Group A versus Group B) was 50 vs 37% (P = NS) and 25 vs 0% (P = NS), respectively. Post-transplant extracorporeal membrane oxygenation was required in 5 and 2 patients in Groups A and B, respectively (P = NS). CONCLUSIONS: The use of initially rejected grafts treated with EVLP does not increase the incidence and severity of PGD after LTx. Although comparison of PGD 3 incidence in the two groups did not reach a statistical difference, all EVLP patients suffering from severe PGD early after transplant recovered normal lung function at 72 h, suggesting a protective role of EVLP against PGD occurrence and severity.

Advanced heart failure in critical patients (INTERMACS 1 and 2 levels): ventricular assist devices or emergency transplantation?

OBJECTIVE: For patients in advanced heart failure, emergency transplantation or ventricular assist devices (VADs) are possible strategies. The aim of this single-centre, retrospective study was to evaluate early and long-term results for these two strategies. METHODS: From 2005 to 2011, we analysed 49 INTERMACS level 1 and 2 patients, who were divided into the following two groups: group A comprised 26 patients on the waiting list for heart transplantation with urgent conditions; and group B comprised 23 patients who underwent VAD implantation as a bridge to candidacy. RESULTS: In group A, 25 patients underwent transplantation. In group B, 19 patients were supported with left VAD and four with biventricular VAD. Of these 23 patients, 13 underwent transplantation (mean time 279 ± 196 days). The 30 day mortality was 42.3 and 4.3% in group A and B, respectively. Survival at 6 and 12 months was significantly better in group B than in group A (87 vs 53%, P = 0.018 at 6 months; and 77 vs 48%, P = 0.045 at 12 months). CONCLUSION: Improved outcomes may justify the use of mechanical assistance devices as a bridge to candidacy or bridge to transplantation in INTERMACS 1 and 2 patients in order to avoid high-risk transplants. Evaluation of long-term multicentre outcomes is needed to assess future strategies.

PPARγ in coronary atherosclerosis: in vivo expression pattern and correlations with hyperlipidemic status and statin treatment.

OBJECTIVE: Peroxisome proliferator-activated receptor-γ (PPARγ) is involved in regulation of macrophage inflammation and in atherosclerosis. Herein we investigate the influence of statin treatment on PPARγ expression in coronary artery disease. METHOD: PPARγ expression was investigated in coronary atherosclerotic atherectomies (N=48) and arteries (N=12) from patients with stable or unstable coronary syndromes or undergoing cardiac transplantation for end-stage ischemic cardiomyopathy, respectively, by immunohistochemistry. Plaque components and tissue factor immunoreactivity were also investigated. Atherectomies were obtained from de novo culprit lesions of hypercholesterolemic (16 statin-treated and 16 untreated) and normolipidemic (N=16) patients. Furthermore, PPARγ expression was evaluated in patients peripheral blood monocytes and in monocytic U937 cells after atorvastatin incubation, by Western blot analysis. RESULT: PPARγ expression was higher in coronary plaques and peripheral blood monocytes of statin-treated patients, and it significantly increased in monocytes after 24h atorvastatin incubation (p<0.05). Intra-plaque macrophage content, atheroma, neoangiogenesis and hemorrhage, and circulating CRP levels were lower in statin-treated than untreated hypercholesterolemic patients and comparable with normolipidemic subjects. PPARγ immunoreactivity was localized to neointima and media, its distribution pattern being different from that of tissue factor. CONCLUSION: PPARγ expression was enhanced in statin-treated patients with different distribution and behavior as compared to atheroma, macrophage content, tissue factor immunoreactivity and serum CRP. In vitro studies showed increased PPARγ expression in monocytes after atorvastatin incubation. These findings provide further evidence as to the protective role of statins in coronary artery disease and their influence on PPARγ expression in coronary plaques and on the inflammatory status of patients.

Nail gun penetrating injury of the heart mimicking an acute coronary syndrome.

We describe the case of a 75-year-old man admitted to hospital for chest pain and syncope. Physical examination was normal with evidence of a very small wound on the left chest. Considering the presence of multiple coronary risk factors, an acute coronary syndrome was initially suspected, but the electrocardiogram (EKG) was normal and only a slight increase of cardiac enzymes was detected. The hypothesis of aortic dissection was also considered and in order to discriminate between the aortic and coronary syndrome, a thoracic and coronary computed tomography (CT) scan was performed. The CT scan showed a metallic structure, suggestive of a nail, about 6 cm in length, in the deep layers of the left ventricular wall and a small pneumothorax due to a lung lesion. The patient was therefore transferred to our department for urgent cardiac surgery that was performed without complications.

Emergent coronary artery bypass grafting for cardiogenic shock caused by very late drug-eluting stent thrombosis.

We describe a case of cardiogenic shock caused by a very late drug-eluting stent (DES) thrombosis. The patient underwent emergent coronary artery bypass grafting (CABG) and was discharged home 15 days after the operation. The incidence of stent restenosis had been reduced by the use of DES, but the Achilles' heel of DES is represented by a higher rate of stent thrombosis. In our case, the DES thrombosis occurred 5 years after its implantation, underlining the importance of prolonged dual antiplatelet therapy. Even though rare, this complication may be life-threatening. We believe that CABG provides better event-free survival than percutaneous coronary intervention in patients with multivessel coronary disease despite the use of DES.