Questing for circadian dependence in ST-segment-elevation acute myocardial infarction: a multicentric and multiethnic study.

RATIONALE: Four monocentric studies reported that circadian rhythms can affect left ventricular infarct size after ST-segment-elevation acute myocardial infarction (STEMI). OBJECTIVE: To further validate the circadian dependence of infarct size after STEMI in a multicentric and multiethnic population. METHODS AND RESULTS: We analyzed a prospective cohort of subjects with first STEMI from the First Acute Myocardial Infarction study that enrolled 1099 patients (ischemic time <6 hours) in Italy, Scotland, and China. We confirmed a circadian variation of STEMI incidence with an increased morning incidence (from 6:00 am till noon). We investigated the presence of circadian dependence of infarct size plotting the peak creatine kinase against time onset of ischemia. In addition, we studied the patients from the 3 countries separately, including 624 Italians; all patients were treated with percutaneous coronary intervention. We adopted several levels of analysis with different inclusion criteria consistent with previous studies. In all the analyses, we did not find a clear-cut circadian dependence of infarct size after STEMI. CONCLUSIONS: Although the circadian dependence of infarct size supported by previous studies poses an intriguing hypothesis, we were unable to converge toward their conclusions in a multicentric and multiethnic setting. Parameters that vary as a function of latitude could potentially obscure the circadian variations observed in monocentric studies. We believe that, to assess whether circadian rhythms can affect the infarct size, future study design should not only include larger samples but also aim to untangle the molecular time-dynamic mechanisms underlying such a relation.

Calcified left ventricular endomyocardial fibrosis.

Endomyocardial fibrosis (EMF) is a rare condition, but in certain tropical countries it is a major cause of illness and death. Moreover, the etiology of the disease is unknown, it has no specific treatment, and it carries a poor prognosis. As both the heart and the peritoneum may be affected by the inflammation and deposition of fibrous tissue, even left ventricular EMF may present with gross ascites mimicking right-heart failure. Notwithstanding attempts to standardize the diagnostic criteria, the clinical presentation may still be challenging. The case is described of calcified left ventricular EMF presenting with right-heart failure in the absence of right ventricular fibrosis.

Echocardiographic patterns of incomplete Shone's syndrome in adults.

BACKGROUND AND AIM OF THE STUDY: Whilst several cases of complete Shone's complex have been reported in children, the incomplete form--characterized by two or three components--has rarely been described in adults. Because of the wide spectrum of severity of each pattern, the correct diagnosis may be challenging. Moreover, as the hemodynamic interdependence between defects is thought to be a major determinant of clinical outcome and long-term follow up, it is crucial to consider the lesions as part of the same Shone's syndrome. METHODS: Between May 2005 and December 2009, six male patients (mean age 38 +/- 8 years) were referred to the authors' institute with progressive worsening of heart failure symptoms related to valvular disease. All patients had a clinical history of surgery for coarctation of the aorta (CoA), and all but one had a bicuspid aortic valve. Standard transthoracic and transesophageal echocardiographies were performed in all patients to identify the valvular heart disease responsible for clinical deterioration. RESULTS: Unexpected findings of dysplastic mitral valvular apparatus compatible with parachute deformity of the mitral valve (PMV) or 'PMV-like' morphology were disclosed in all patients. The association with major anatomic abnormalities (bicuspid aortic valve, subaortic ridge, and previous CoA surgical repair) was highly suggestive of adult incomplete Shone's syndrome. CONCLUSION: The findings of the present case series emphasized the need for a greater awareness regarding the rare incomplete Shone's syndrome in adulthood, as it occurs far more frequently than might be expected following a random diagnosis. The findings also highlight the additional value of a carefully performed step-by-step echocardiographic study to support the clinical decision-making in this array of left heart anomalies.

[Acute coronary syndrome after insect bites: a systematic review of available literature]. / Sindrome coronarica acuta dopo puntura di insetto: una revisione sistematica della letteratura.

BACKGROUND: Kounis syndrome is a hypersensitivity coronary disorder induced by exposure to several triggers; the most common are antibiotics, followed by insect bites. METHODS: We reviewed the literature and identified 66 patients who experienced acute coronary syndrome after insect bites. RESULTS: The median age was 51 years, and 19.0% were women and only 12% had a history of allergy. The most involved insects were bee and wasp (86%) and the most frequent clinical manifestations were chest pain and anaphylaxis (36% and 29%, respectively). ST-segment elevation was the most common electrocardiographic finding (>70%). There was a not negligible rate of complications (15%), with a possible increased arrhythmic burden in patients without significant coronary atherosclerosis. CONCLUSIONS: Acute coronary syndrome after insect bites is not so rare and it could have serious complications, with a possible increased arrhythmic burden in patients without significant coronary atherosclerosis.

Expansion of T-cell receptor zeta dim effector T cells in acute coronary syndromes.

OBJECTIVE: The T-cell receptor zeta (TCR zeta)-chain is a master sensor and regulator of lymphocyte responses. Loss of TCR zeta-chain expression has been documented during infectious and inflammatory diseases and defines a population of effector T cells (TCR zeta(dim) T cells) that migrate to inflamed tissues. We assessed the expression and functional correlates of circulating TCR zeta(dim) T cells in coronary artery disease. METHODS AND RESULTS: We examined the expression of TCR zeta-chain by flow cytometry in 140 subjects. Increased peripheral blood CD4(+) TCR zeta(dim) T cells were found in patients with acute coronary syndromes (ACS, n=66; median 5.3%, interquartile 2.6 to 9.1% of total CD4(+) T cells; P<0.0001) compared to chronic stable angina (CSA, n=32; 1.6%; 1.0 to 4.1%) and controls (n=42; 1.5%; 0.5 to 2.9%). Such increase was significantly greater in ACS patients with elevated levels of C-reactive protein, and it persisted after the acute event. Moreover, TCR zeta(dim) cells were also more represented within CD8(+) T cell, NK, and CD4(+)CD28(null) T cell subsets in ACS compared to CSA and controls. Finally, CD4(+) and CD8(+) TCR zeta(dim) T cells isolated from ACS displayed an enhanced transendothelial migratory capacity. CONCLUSIONS: TCR zeta(dim) T cells, an effector T-cell subset with transendothelial migratory ability, are increased in ACS, and may be implicated in coronary instability.

Outcomes after sudden cardiac arrest in sports centres with and without on-site external defibrillators.

OBJECTIVE: Sudden cardiac arrest (SCA) is a rare but tragic event during amateur sports activities. Our aim is to analyse whether availability of automated external defibrillators (AEDs) in amateur sports centres could impact on SCA survival. METHODS: This is an observational study. During an 18-year period, data regarding exercise-related SCA in sports centres were prospectively collected. Survival rates and time to response were compared between centres with an AED already available and centres where an AED was not already present. RESULTS: Out of 252 sports facilities, 207 (82%) acquired an AED during follow-up while 45 (18%) did not. From 1999 to 2014, there were 26 SCAs (24 (92%) men, 54±17 years old) with 15 (58%) of them in centres with on-site AED. Neurologically intact survival rates were 93% in centres with on-site AED and 9% in centres without (P<0.001). Presence of on-site AED, presence of shockable rhythm, first assistance by a lay bystander and time to defibrillation were all related to neurological intact survival, but the presence of on-site AED was the only independent predictor in the multivariate analysis. The use of on-site AED resulted in a lower time to first shock when compared with emergency medical system-delivered AED (3.3±1.4min vs 7.3±3.2 min; P=0.001). CONCLUSIONS: The presence of on-site AEDs is associated with neurologically intact survival after an exercise-related SCA. Continuous efforts are recommended in order to introduce AEDs in sports and fitness centres, implement educational programmes and increase common awareness about SCA.

Heart surgery for immigrants in Italy: burden of cardiovascular disease, adherence to treatment and outcomes.

AIM: Italy is a country with high rates of immigration and the knowledge of immigrant health is very fragmentary. We provide a current picture of cardiovascular disease causes and clinical outcomes following heart surgery. METHODS: A clinical and echocardiographic survey was conducted on 154 consecutive immigrants referred for heart surgery to San Raffaele Hospital in Milan between 2003 and 2011. RESULTS: Major causes of heart disease were rheumatic heart disease (RHD) (n = 64, 41%), nonrheumatic valvulopathies (n = 41, 27%), ischemic heart disease (IHD) (n = 25, 16%), congenital heart disease (n = 13, 9%) and miscellaneous (n = 11, 7%). Median age was 49 years [interquartile range (IQR) 7-81]; 55% of patients were male. Among valvulopathies, rheumatic mitral disease was predominant (n = 56, 53%) as both single and multivalvular disease (n = 46, 73%); myxomatous prolapse emerged as the second main pattern of mitral disease (n = 30, 33%). Among patients with IHD, 72% had a high cardiovascular risk. Surgery was scheduled in 138 patients (90%). Clinical follow-up was available in 96 patients (62%) [median time 62 months (IQR 15-123)], among whom 92 (96%) were alive, four patients (4%) had died and 58 (38%) were lost. CONCLUSION: Cardiovascular diseases represent a major health topic among immigrants in developed countries. RHD still is the predominant cause of hospitalization for heart surgery, nonrheumatic valvulopathies and IHD emerging as second and third causes, respectively. Data underline the need of reinforcement of prevention and care strategies in the matter of immigrant health and warrant the urgent attention of the international public health and research communities.

Cardiac surgery for patients with heart failure due to structural heart disease in Uganda: access to surgery and outcomes.

OBJECTIVE: Few data are available on heart failure (HF) in sub-Saharan Africa. We aimed to provide a current picture of HF aetiologies in urban Uganda, access to heart surgery, and outcomes. METHODS: We prospectively collected clinical and echocardiographic data from 272 consecutive patients referred for suspected heart disease to a tertiary hospital in Kampala during seven non-governmental organisation (NGO) missions from 2009 to 2013. We focused the analysis on 140 patients who fulfilled standardised criteria of HF by echocardiography. RESULTS: Rheumatic heart disease (RHD) was the leading cause of HF in 44 (31%) patients. Among the 50 children included (age ≤ 16 years), congenital heart disease (CHD) was the first cause of HF (30 patients, 60%), followed by RHD (16 patients, 32%). RHD was the main cause of HF (30%) among the 90 adults. All 85 patients with RHD and CHD presented with an indication for heart surgery, of which 74 patients were deemed fit for intervention. Surgery was scheduled in 38 patients with RHD [86%, median age 19 years (IQR: 12-31)] and in 36 patients with CHD [88%, median age 4 years (IQR 1-5)]. Twenty-seven candidates (32%) were operated on after a median waiting time of 10 months (IQR 6-21). Sixteen (19%) had died after a median of 38 months (IQR 5-52); 19 (22%) were lost to follow up. CONCLUSION: RHD still represents the leading cause of HF in Uganda, in spite of cost-efficient prevention strategies. The majority of surgical candidates, albeit young, do not have access to treatment and present high mortality rates.

Clinical outcome and quality of life in octogenarians following transcatheter aortic valve implantation (TAVI) for symptomatic aortic stenosis.

OBJECTIVE: TAVI is the alternative option in pts with AS deemed ineligible for surgery. Although mortality and morbidity are measures to assess the effectiveness of treatments, quality of life (QOL) should be an additional target. We assessed clinical outcome and QOL in octogenarians following TAVI. DESIGN: All octogenarians with a risk profile considered by the Heart Team to be unacceptable for surgery entered in this registry. QOL was assessed by questionnaires concerning physical and psychic performance. PATIENTS: A hundred forty-five octogenarians (age: 84.7 ± 3.4 years; male: 48.3%) underwent TAVI for AS (97.2%) or isolated AR (2.8%). NYHA class: 2.8 ± 0.6; Logistic EuroScore: 26.1 ± 16.7; STS score: 9.2 ± 7.7.Echocardiographic assessments included AVA (0.77 ± 0.21 cm2), mean/peak gradients (54.5 ± 12.2/88 ± 19.5 mm Hg), LVEF (21%=EF ≤ 40%), sPAP (43.1 ± 11.6 mmHg). INTERVENTIONS: All pts underwent successful TAVI using Edward-SAPIEN valve (71.2%) or Medtronic CoreValve (28.8%). MAIN OUTCOME MEASURES: Rates of mortality at 30 days, 6 months and 1 year were 2.8%, 11.2% and 17.5%. RESULTS: At 16-month follow up, 85.5% survived showing improved NYHA class (2.8 ± 0.6 vs 1.5 ± 0.7; p<0.001), decreased sPAP (43.1 ± 11.6 mm Hg vs 37.1 ± 7.7 mm Hg; p<0.001) and increased LVEF in those with EF ≤ 40% (34.9 ± 6% vs 43.5 ± 14.4%; p=0.006). Concerning QOL, 49% walked unassisted, 79% (39.5% among pts ≥ 85 years) reported self-awareness improvement; QOL was reported as "good" in 58% (31.4% among pts ≥ 85 years), "acceptable according to age" in 34% (16% among pts ≥ 85 years) and "bad" in 8%. CONCLUSION: TAVI procedures improve clinical outcome and subjective health-related QOL in very elderly patients with symptomatic AS.

Surgical outcome of partial Shone complex.

Partial forms of Shone complex are rare. Surgical outcomes of the complete forms have generally been poor, whereas there is a lack of data on long-term follow-up of surgically treated adult partial complex. Between 2001 and 2011, nine patients (age: 38 ± 8 years; six males, 67%) were referred for valvular heart disease. Transthoracic and transoesophageal echocardiography was performed. Data were confirmed by intra-operative findings and reports. Patients were diagnosed as partial Shone complex and presented with mitral stenosis (MS) (45%) or mitral regurgitation (22%) or aortic regurgitation (22%). All but one patient (89%) reported previous surgery: coarctation of the aorta repair (87.5%) and aortic valvulotomy (12.5%). Redo intervention included: mitral valve replacement (25%), mitral repair (25%), aortic valve replacement (37.5%) and subvalvular aortic ridge resection (25%). One patient refused surgery. Patients surgically treated before the age of 5 (87.5%) showed favourable outcome (survival rate: 100%) and a 23.6 (± 4.6)-year follow-up free from events. The patient who underwent first intervention at the age of 50 and the patient with MS who refused surgery showed a 45 (± 7)-year follow-up free from major morbidity. Patients with partial Shone complex, properly diagnosed and treated, show favourable surgical outcome free from major clinical events.

Dynamic assessment of 'valvular reserve capacity' in patients with rheumatic mitral stenosis.

AIMS: Mitral stenosis (MS) may exhibit a dynamic valvular reserve. When resting gradients and systolic pulmonary pressure (sPAP) do not reflect the real severity of the disease, a dynamic evaluation becomes necessary. The aim of the study was to assess the clinical utility of exercise echocardiography in symptomatic patients with apparently subcritical MS. METHODS AND RESULTS: One hundred and thirty consecutive patients were referred for symptomatic MS. Patients with unimpressive resting MVA (>1-1.5 cm(2)) and mean PG (≥5-9 mmHg) underwent exercise echocardiography. Cardiac performance and mitral indices (MVA, peak/mean PG, sPAP) were measured. Exhaustion of valvular reserve capacity under exercise was defined as appearance of symptoms and sPAP > 60 mmHg. Forty-six patients (35%) (age: 53 ± 10 years; 74%, female) with resting MVA (1.2 ± 0.36 cm(2)), mean PG (6.8 ± 2.7 mmHg), and sPAP (38 ± 7 mmHg) inconsistent with symptoms underwent stress echocardiography. Exercise was stopped for dyspnoea (76%) or fatigue (24%). At peak workloads (57.2 ± 21.8 Watts), increased mean PG (17.2 ± 4.8 mmHg, P< 0.001) and sPAP (67.4 ± 11.4 mmHg; P< 0.0001) were observed, without change in MVA (1.25 ± 0.4 cm(2); P= n.s.). At univariate analysis, predictors of adaptation to exercise were age (-0.345; P = 0.024), mean PG (0.339; P= 0.023), and sPAP (0.354; P= 0.024); at multivariate analysis, best predictor was resting mean PG, although correlation was poor (-0.339; P= 0.015). CONCLUSION: In MS with limiting symptoms despite unimpressive findings at rest, valvular capacity exhaustion should be tested on a dynamic background, as no single resting index can predict potential haemodynamic adaptation to exercise. In such context, the contribution of exercise echocardiography remains extremely valuable.

Tracking antigen-experienced effector T cells in vitro and in vivo.

The TCR complex is a multisubunit complex, comprising at least eight transmembrane units. The clonotypic TCR alpha and beta chains are responsible for antigen recognition, whilst the invariant chains of the CD3 complex (delta, epsilon and gamma) and two zeta (zeta) polypeptides couple antigen recognition to downstream signal transduction pathways. TCRzeta (CD247) functions as an amplification module in the TCR signalling cascade and is also essential for the assembly and surface expression of the TCR/CD3 complex. Loss of TCRzeta expression is common in chronic infectious and inflammatory diseases, as well as in cancer. Previous work has indicated that TCRzeta(low)-expressing cells phenotypically resemble antigen-experienced effector T cells. Here, we describe the derivation of a flow cytometry-based TCRzeta expression index for the purpose of more precisely defining TCRzeta expression, in addition to utilising a simple transmigration assay in the demonstration that TCRzeta(dim) T cells have intrinsic migratory properties that may explain their accumulation at sites of inflammation.

TCRzetadim lymphocytes define populations of circulating effector cells that migrate to inflamed tissues.

The T-cell receptor zeta (TCRzeta) chain is a master sensor and regulator of lymphocyte responses. Loss of TCRzeta expression has been documented in infectious, inflammatory, and malignant diseases, suggesting that it may serve to limit T-cell reactivity and effector responses at sites of tissue damage. These observations prompted us to explore the relationship between TCRzeta expression and effector function in T cells. We report here that TCRzeta(dim) lymphocytes are enriched for antigen-experienced cells refractory to TCR-induced proliferation. Compared to their TCRzeta(bright) counterparts, TCRzeta(dim) cells share characteristics of differentiated effector T cells but use accessory pathways for transducing signals for inflammatory cytokine gene expression and cell contact-dependent pathways to activate monocytes. TCRzeta(dim) T cells accumulate in inflamed tissues in vivo and have intrinsic migratory activity in vitro. Whilst blocking leukocyte trafficking with anti-TNF therapy in vivo is associated with the accumulation of TCRzeta(dim) T cells in peripheral blood, this T-cell subset retains the capacity to migrate in vitro. Taken together, the functional properties of TCRzeta(dim) T cells make them promising cellular targets for the treatment of chronic inflammatory disease.