Antonio Iaconelli

Effects of bariatric surgery on cardiac remodeling: Clinical and pathophysiologic implications

Purpose: To assess the effects of bariatric surgery (BS) on cardiac mass, volumes and function as compared to persistent morbid obesity. Although beneficial effects of weight loss on cardiac function have been reported, systematic studies on the effect of BS as compared to persistent morbid obesity are lacking. Methods: One-hundred morbidly obese patients (body mass index -BMI- 47.7±7 kg/m2) referred for BS prospectively underwent an echocardiogram: 65 underwent BS and 35 did not. Fifty-one operated and 29 non-operated patients underwent repeat imaging after 2 years. Results: Operated patients showed a significant decrease in weight and BMI paralleled by a significant reduction of left ventricular (LV) mass (from 222.9±52.2 to 207.7±50g) and LV end-diastolic and end-systolic volumes (LVEDV from 124.6±29.3 to 119.4±28.7 and LVESV from 55.3±16.5 to 49.4±15ml) and by a significant increase of LV ejection fraction (from 55.9±4.8 to 59.2±4.4%). In contrast, in non-operated patients LV mass (from 226.5±71.4 to 241.4±94.7g), volumes [LVEDV from 52.8±5.1 to 54.2±6.6 and LVESV from 32.1±3.5 to 34.9±6ml] significantly increased and ejection fraction deteriorated (from 57.1±5.1 to 54.7±7.4%). At multivariate analysis, BS was the only significant predictor of change in LV end-systolic volume while weight change predicted change in LV mass. Conclusions: In extreme obesity the sustained weight loss achieved with BS is associated to an improvement of cardiac structure and function, while persistent severe obesity is associated to progressive deterioration. These favorable cardiac effects associated to previously described positive metabolic effects make BS an attractive therapeutic option in this setting of patients.

Coronary Artery Aneurysms Presenting as Acute Coronary Syndrome: An Unusual Case of IgG4-Related Disease Vascular Involvement

We report the case of a 65-year-old man referred to our department because of a complex coronary aneurysmal disease presenting as subacute ST-segment elevation myocardial infarction due to intraluminal thromboembolism. The patients past medical history (recurrent episodes of lymphadenopathies, parotid swelling, prostatitis, and dacryoadenitis) raised the suspicion of a unifying systemic disorder with coronary involvement. An extensive infectious and autoimmune screening was performed, leading to the final diagnosis of IgG4-related disease. Our case highlights the importance to include this rare and recently described disease in the diagnostic workup of acquired coronary aneurysms.

Atorvastatin inhibits the immediate-early response gene EGR1 and improves the functional profile of CD4+T-lymphocytes in acute coronary syndromes

Background- Adaptive immune-response is associated with a worse outcome in acute coronary syndromes. Statins have anti-inflammatory activity beyond lowering lipid levels. We investigated the effects of ex-vivo and in-vivo atorvastatin treatment in acute coronary syndromes on CD4+T-cells, and the underlying molecular mechanisms. Approach and results- Blood samples were collected from 50 statin-naïve acute coronary syndrome patients. We assessed CD4+T-cell activation by flow-cytometry, the expression of 84 T-helper transcription-factors and 84 T-cell related genes by RT-qPCR, and protein expression by Western-blot, before and after 24-hours incubation with increasing doses of atorvastatin: 3-10-26 g/ml (corresponding to blood levels achieved with doses of 10-40-80 mg, respectively). After incubation, we found a significant decrease in interferon-?-producing CD4+CD28nullT-cells (P = 0.009) and a significant increase in interleukin-10-producing CD4+CD25highT-cells (P < 0.001). Atorvastatin increased the expression of 2 genes and decreased the expression of 12 genes (in particular, EGR1, FOS,CCR2 and toll like receptor-4; >3-fold changes). The in-vivo effects of atorvastatin were analyzed in 10 statin-free acute coronary syndrome patients at baseline, and after 24h and 48h of atorvastatin therapy (80 mg/daily): EGR1-gene expression decreased at 24h (P = 0.01) and 48h (P = 0.005); EGR1-protein levels decreased at 48h (P = 0.03). Conclusions-In acute coronary syndromes, the effects of atorvastatin on immune system might be partially related to the inhibition of the master regulator gene EGR1. Our finding might offer a causal explanation on why statins improve the early outcome in acute coronary syndromes.

HYALURONIC ACID, HYALURONIDASE-2 AND ACUTE CORONARY SYNDROMES: POSSIBLE CORRELATION WITH PLAQUE EROSION

Background: A recent experimental model of plaque instability suggests that endothelial activation and the exposure of the extracellular matrix are involved in the inflammatory process of plaque erosion. These data, together with the notion of an intense immunostaining on eroded autoptic coronary

Anderson-Fabry’s Disease: A Rare but Treatable Case of Fever of Unknown Origin

Anderson-Fabry’s disease (AFD) is a rare, X-linked lysosomal storage disorder caused by the complete deficiency or attenuated activity of the enzyme α-galactosidase A, leading to progressive systemic intracellular accumulation of glycosphingolipids and subsequent cellular dysfunction, inflammation and fibrosis. Fever is a frequently misinterpreted symptom in the early stages of the disease, leading to diagnostic delay. We present the case of a 35-year-old man admitted to our Periodic Fever Research Centre for long-lasting recurrent episodes of fever of unknown origin. After extensive assessment, we diagnosed AFD associated with a novel GLA mutation. We started enzyme replacement therapy with clinical benefit and complete remission of fever. LEARNING POINTS Anderson-Fabry’s Disease (AFD) is an inherited lysosomal storage disorder, in which progressive multi-organ glycosphingolipid accumulation leads to multi-systemic dysfunction. Diagnosis requires a high level of suspicion as the clinical presentation can be very heterogeneous. As fever is an early uncommon symptom causing diagnostic delay, it is important to consider AFD in the differential diagnosis of recurrent fevers, particularly when febrile episodes are not associated with an increase in acute phase reactants and when other signs or symptoms suggestive of AFD are present. Prognosis depends on an early diagnosis because promptly initiation of enzyme replacement therapy (ERT) can prevent the progression of organ damage. In our case fever disappeared after ERT initiation, a finding not previously reported to our knowledge. Therefore, fever remission could be an early marker of response to ERT.

Response to Letter Regarding Article, “Growth Properties of Cardiac Stem Cells Are a Novel Biomarker of Patients’ Outcome After Coronary Bypass Surgery”

We appreciate the interest of Drs Li and Shen in our study,1 which emphasizes the critical role that the insulin-like growth factor-1 (IGF-1) and IGF-1 receptor system has in defining the growth properties of human cardiac stem cells (hCSCs). We shared their view that IGF-1 positively interferes with the consequences of diabetes mellitus and dyslipidemia, and possibly with other cardiovascular pathologies. Based on our interest in IGF-1, a transgenic mouse model with cardiomyocyte-restricted overexpression of IGF-1 was developed.2 With this strategy, an increase in the number of ventricular myocytes was obtained, resulting in a significantly lower systolic and diastolic stress at the cellular level, together with an enhanced ability of the myocardium to sustain increases in pressure or volume loads. Overexpression of IGF-1 prevents the manifestation of the diabetic myopathy and is associated with a …

Effects of bariatric surgery on cardiac remodeling: clinical and pathophysiologic implications

Purpose: To assess the effects of bariatric surgery (BS) on cardiac mass, volumes and function as compared to persistent morbid obesity. Although beneficial effects of weight loss on cardiac function have been reported, systematic studies on the effect of BS as compared to persistent morbid obesity are lacking. Methods: One-hundred morbidly obese patients (body mass index -BMI- 47.7±7 kg/m2) referred for BS prospectively underwent an echocardiogram: 65 underwent BS and 35 did not. Fifty-one operated and 29 non-operated patients underwent repeat imaging after 2 years. Results: Operated patients showed a significant decrease in weight and BMI paralleled by a significant reduction of left ventricular (LV) mass (from 222.9±52.2 to 207.7±50g) and LV end-diastolic and end-systolic volumes (LVEDV from 124.6±29.3 to 119.4±28.7 and LVESV from 55.3±16.5 to 49.4±15ml) and by a significant increase of LV ejection fraction (from 55.9±4.8 to 59.2±4.4%). In contrast, in non-operated patients LV mass (from 226.5±71.4 to 241.4±94.7g), volumes [LVEDV from 52.8±5.1 to 54.2±6.6 and LVESV from 32.1±3.5 to 34.9±6ml] significantly increased and ejection fraction deteriorated (from 57.1±5.1 to 54.7±7.4%). At multivariate analysis, BS was the only significant predictor of change in LV end-systolic volume while weight change predicted change in LV mass. Conclusions: In extreme obesity the sustained weight loss achieved with BS is associated to an improvement of cardiac structure and function, while persistent severe obesity is associated to progressive deterioration. These favorable cardiac effects associated to previously described positive metabolic effects make BS an attractive therapeutic option in this setting of patients.