Anna Chiara Vermi

Effector Memory T cells Are Associated With Atherosclerosis in Humans and Animal Models

Background— Adaptive T-cell response is promoted during atherogenesis and results in the differentiation of naïve CD4+T cells to effector and/or memory cells of specialized T-cell subsets. Aim of this work was to investigate the relationship between circulating CD4+T-cell subsets and atherosclerosis. Methods and Results— We analyzed 57 subsets of circulating CD4+T cells by 10-parameter/8-color polychromatic flow cytometry (markers: CD3/CD4/CD45RO/CD45RA/CCR7/CCR5/CXCR3/HLA-DR) in peripheral blood from 313 subjects derived from 2 independent cohorts. In the first cohort of subjects from a free-living population (n=183), effector memory T cells (TEM: CD3+CD4+CD45RA−CD45RO+CCR7− cells) were strongly related with intima-media thickness of the common carotid artery, even after adjustment for age (r=0.27; P<0.001). Of note, a significant correlation between TEM and low-density lipoproteins was observed. In the second cohort (n=130), TEM levels were significantly increased in patients with chronic stable angina or acute myocardial infarction compared with controls. HLA-DR+TEM were the TEM subpopulation with the strongest association with the atherosclerotic process (r=0.37; P<0.01). Finally, in animal models of atherosclerosis, TEM (identified as CD4+CD44+CD62L−) were significantly increased in low-density lipoprotein receptor and apolipoprotein E deficient mice compared with controls and were correlated with the extent of atherosclerotic lesions in the aortic root (r=0.56; P<0.01). Conclusions— Circulating TEM cells are associated with increased atherosclerosis and coronary artery disease in humans and in animal models and could represent a key CD4+T-cell subset related to the atherosclerotic process. (J Am Heart Assoc. 2012;1:27-41.)

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.

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.

Expansion of T-Cell Receptor ζdim Effector T Cells in Acute Coronary Syndromes

Objective—The T-cell receptor zeta (TCR&zgr;)-chain is a master sensor and regulator of lymphocyte responses. Loss of TCR&zgr;-chain expression has been documented during infectious and inflammatory diseases and defines a population of effector T cells (TCR&zgr;dim T cells) that migrate to inflamed tissues. We assessed the expression and functional correlates of circulating TCR&zgr;dim T cells in coronary artery disease. Methods and Results—We examined the expression of TCR&zgr;-chain by flow cytometry in 140 subjects. Increased peripheral blood CD4+ TCR&zgr;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&zgr;dim cells were also more represented within CD8+ T cell, NK, and CD4+CD28null T cell subsets in ACS compared to CSA and controls. Finally, CD4+ and CD8+ TCR&zgr;dim T cells isolated from ACS displayed an enhanced transendothelial migratory capacity. Conclusions—TCR&zgr;dim T cells, an effector T-cell subset with transendothelial migratory ability, are increased in ACS, and may be implicated in coronary instability.

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

Summary 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. Conclusions 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.

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 Valve Involvement in Systemic Diseases: A Review

Increasing age and new trends of mixed populations have newly aroused interest in valvular heart disease in the developed countries still in need of new clinical insights. In the clinical setting of systemic diseases, the proper assessment of cardiovascular abnormalities may be challenging, and the characterization of valvular involvement might help to recognize the underlying disease and cardiac sequelae. Prompt identification of valvular lesions may, therefore, also be useful for differential diagnosis. This article reviews the cardiac involvement in systemic diseases from etiology and background definition to echocardiographic assessment and clinical interpretation.

Multimodality imaging of iatrogenic pulmonary vein stenosis

Pulmonary vein stenosis after radiofrequency ablation occurs up to 3% and requires prompt diagnosis and treatment. Since clinical presentation is variable, a multimodality imaging approach currently provides an essential framework to address the diagnosis and appropriate treatment. A 40-year-old woman who had undergone surgical correction of sinus venosus atrial septal defect and partial anomalous pulmonary vein return required …