Angelo Cioppa

Genetic polymorphisms in XRCC1, OGG1, APE1 and XRCC3 DNA repair genes, ionizing radiation exposure and chromosomal DNA damage in interventional cardiologists

Interventional cardiologists working in high-volume cardiac catheterization laboratory are exposed to significant occupational radiation risks. Common single-nucleotide polymorphisms (SNPs) in DNA repair genes are thought to modify the effects of low-dose radiation exposure on DNA damage, the main initiating event in the development of cancer and hereditary disease. The aim of this study was to determine the relationship between XRCC1 (Arg194Trp and Arg399Gln), OGG1 (Ser326Cys), APE1 (Asp148Glu) and XRCC3 (Thr241Met) SNPs and chromosomal DNA damage. We enrolled 77 subjects: 40 interventional cardiologists (27 male, 41.3+/-9.4 years and 13 female, 37.8+/-8.4 years) and 37 clinical cardiologists (26 male, 39.4+/-9.5 years and 11 female, 35.0+/-9.8 years) without radiation exposure as the control group. Micronucleus (MN) assay was performed as biomarker of chromosomal DNA damage and an early predictor of cancer. MN frequency was significantly higher in interventional cardiologists than in clinical physicians (19.7+/-7.8 per thousand vs. 13.5+/-6.3 per thousand, p=0.0003). Within the exposed group, individuals carrying a XRCC3 Met241 allele had higher frequency than homozygous XRCC3 Thr241 (21.2+/-7.8 per thousand vs. 16.6+/-7.1 per thousand, p=0.03). Individuals with two or more risk alleles showed a higher MN frequency when compared to subjects with one or no risk allele (18.4+/-6.6 per thousand vs. 14.4+/-6.1 per thousand, p=0.02). An interactive effect was found between smoking, exposure >10 years and the presence of the two or more risk alleles on the MN frequency (F=6.3, p=0.02). XRCC3 241Met alleles, particularly in combination with multiple risk alleles of DNA repair genes, contribute to chromosomal DNA damage levels in interventional cardiologists.

Cellular adaptive response to chronic radiation exposure in interventional cardiologists

Aims Invasive cardiologists are the most exposed to ionizing radiation among health professionals and show an increased rate of somatic DNA damage. To evaluate the effects of chronic low-dose exposure to ionizing radiation on redox state and apoptotic activation. Methods and results We enrolled 10 healthy exposed professionals (all interventional cardiologists, Group II, exposed: age = 38 ± 5 years) and 10 age- and gender-matched unexposed controls (Group I, non-exposed). Exposed subjects had a median exposure of 4 mSv/year (range 1-8) by film badge dosimetry (below lead apron). We measured reduced glutathione (GSH, a marker of antioxidant response) in erythrocytes and plasma generation of hydrogen peroxide (a marker of oxyradical stress) by ferrous oxidation-xylenol orange assay in plasma. In both groups, lymphocytes were isolated and caspase-3 activity (a marker of apoptotic response) measured at baseline and following 2 Gy in vitro irradiation. Exposed subjects showed a three-fold increase in hydrogen peroxide (Group I = 2.21 ± 1.03 vs. II = 6.51 ± 1.55 μM H(2)O(2) equivalents) and a 1.7-fold increase in GSH (I = 12.37 ± 1.22 vs. II = 20.61 ± 2.16 mM). Exposed subjects also showed higher values of caspase-3 activity, both at baseline and-more strikingly-following high-dose radiation challenge. Conclusion In interventional cardiologists, chronic exposure to low-dose radiation is associated with an altered redox balance mirrored by an increase in hydrogen peroxide and with two possibly adaptive cellular responses: (i) an enhanced antioxidant defence (increase in GSH, counteracting increased oxyradical stress) and (ii) an increased susceptibility to apoptotic induction which might efficiently remove genetically damaged cells.

Management strategies in patients affected by chronic total occlusions: results from the Italian Registry of Chronic Total Occlusions

BACKGROUNDnThrough contemporary literature, the optimal strategy to manage coronary chronic total occlusions (CTOs) remains under debate.nnnOBJECTIVESnThe aim of the Italian Registry of Chronic Total Occlusions (IRCTO) was to provide data on prevalence, characteristics, and outcome of CTO patients according to the management strategy.nnnMETHODSnThe IRCTO is a prospective real world multicentre registry enrolling patients showing at least one CTO. Clinical and angiographic data were collected independently from the therapeutic strategy [optimal medical therapy (MT), percutaneous coronary intervention (PCI), or coronary artery bypass grafting (CABG)]; a comparative 1-year clinical follow-up was performed.nnnRESULTSnA total of 1777 patients were enrolled for an overall CTO prevalence of 13.3%. The adopted therapeutic strategies were as follows: MT in 826 patients (46.5%), PCI in 776 patients (43.7%), and CABG in the remaining 175 patients (9.8%). At 1-year follow-up, patients undergoing PCI showed lower rate of major adverse cardiac and cerebrovascular events (MACCE) (2.6% vs. 8.2% and vs. 6.9%; P < 0.001 and P < 0.01) and cardiac death (1.4% vs. 4.7% and vs. 6.3%; P < 0.001 and P < 0.001) in comparison with those treated with MT and CABG, respectively. After propensity score-matching analysis, patients treated with PCI showed lower incidence of cardiac death (1.5 vs. 4.4%; P < 0.001), acute myocardial infarction (1.1 vs. 2.9%; P = 0.03), and re-hospitalization (2.3 vs. 4.4% P = 0.04) in comparison with those managed by MT.nnnCONCLUSIONSnOur data showed how CTO PCI might significantly improve the survival and decrease MACCE occurrence at 1 year follow-up in comparison with MT and/or CABG.

Excimer laser in acute myocardial infarction: Single centre experience on 66 patients

BACKGROUNDnPulsed-wave ultraviolet excimer laser light at 308 nm can vaporise thrombus, suppress platelet aggregation, and, unlike other thrombectomy devices, ablates the underlying plaque.nnnAIMnTo evaluate both safety and efficacy of laser ablation in patients presenting with Acute Myocardial Infarction (AMI) complicated by persistent thrombotic occlusion.nnnMETHODSnFrom May 2003 to October 2006, we enrolled 66 AMI patients (age 59+/-11 years; 57 men) presenting complete thrombotic occlusion of the infarct related vessel. All patients were treated with laser. Primary acute angiographic end-points was corrected TIMI frame count. Secondary echocardiographic end-point was left ventricular remodeling defined as an increase in end-diastolic volume >/=20% 6 months after infarction. Tertiary clinical endpoint was event-free survival at 6 months follow-up.nnnRESULTSnThere were no intra-procedural death or coronary perforation. One primary angiographic failure was observed during lasing. Major dissection occurred in 1 (1.5%) and distal embolization in 4 patients (6%). Corrected TIMI frame count was 100 at baseline, 29+/-0.6 after lasing and 22+/-3 after stenting. At 6-months follow-up, left ventricular remodeling occurred in 8% patients. Event-free survival was 95% at 6-months follow-up.nnnCONCLUSIONnLaser angioplasty is feasible, safe and effective for the challenging treatment of patients with AMI and thrombus-laden lesions. The acute effects on coronary epicardial and myocardial reperfusion are excellent.

N-acetyl cysteine reduces chromosomal DNA damage in circulating lymphocytes during cardiac catheterization procedures: A pilot study

BACKGROUNDnN-acetylcysteine (NAC) is considered a promising radio-protector for its antioxidant and anticarcinogenic properties. We examined the ability of NAC to confer protection against radiation-induced chromosomal DNA damage during cardiac catheterization procedures.nnnMETHODSnSixty-five patients (52 males, age 64.4 ± 11.9 years) undergoing invasive cardiovascular procedures (peripheral transluminal angioplasty, n=45; cardiac resynchronization therapy, n=15 and ablation therapy n=5) were enrolled: 35 patients (26 males, age 63.4 ± 11.1 years) received the standard hydration protocol consisting of intravenous isotonic saline for 12h after catheterization (Group I), and 30 patients (26 males, age 65.5 ± 12.9 years) received a clinically driven double intravenous dose of NAC (6 mg/kg/h diluted in 250 mL of NaCl 0.9%) for 1h before and a standard dose (6 mg/kg/h diluted in 500 mL of NaCl 0.9%) for 12h following catheterization (Group II). Micronucleus assay (MN) was performed as biomarker of chromosomal DNA damage before, 2 and 24h after the radiation exposure. Dose-area product (DAP; Gy cm(2)) was assessed as physical measure of radiation load.nnnRESULTSnDAP was higher in NAC-treated patients (I=54.7 ± 23.6 vs II=126.2 ± 79.2 Gy cm(2), p=0.0001). MN frequency was 13.7 ± 4.7 ‰ at baseline and showed a significant rise at 2h (18.0 ± 6.8 p=0.01) and 24h (17.6 ± 5.9, p=0.03) in the Group I. There was no significant increase of MN in the Group II (13.7 ± 7.0, 15.5 ± 6.0 and 14.9 ± 6.3 for baseline, 2h and 24h respectively, p=0.4).nnnCONCLUSIONnNAC treatment given to prevent contrast-induced nephropathy may also reduce DNA damage induced by ionizing radiation exposure during cardiac catheterization procedures.

Prosthesis depth and conduction disturbances after last generation balloon-expandable transcatheter aortic valve implantation

AimsnPreliminary data on Sapien 3 valve (S3-THV) use for transcatheter aortic valve implantation have shown an increased permanent pacemaker implantation (PPMI) rate with respect to Sapien XT valve. Aim of this study was to investigate the role of S3-THV position in the left ventricular outflow tract (LVOT) on electrocardiographic changes suggestive of atrioventricular (ΔPR) and/or intraventricular (ΔQRS) conduction abnormalities and 30 days PPMI rate.nnnMethods and resultsnEighty-six consecutive patients treated with S3-THV were included in the study. All patients underwent clinical and electrocardiogram evaluation. Left ventricular outflow tract prosthesis depth was assessed by fluoroscopy and expressed quantitatively (mm) and as aorto-ventricular ratio (AVR). Eight patients (9.3%) needed PPMI at 30 days. A low AVR (≤60/40) predicted PPMI (OR = 6.09, 95% CI 1.19-31.01, P = 0.030) and resulted into higher PPMI rate, compared with higher AVR (30.0 vs. 6.6%, P = 0.017). For each millimetre increase in the LVOT prosthesis depth PPMI risk increased by 1.41 times (95% CI 1.06-1.87, P = 0.017). In patients with low AVR, ΔPR was higher than in those with higher AVR (33.4 ± 56.7 vs. 12.1 ± 19.4 ms, P = 0.021) and ΔPR was associated to LVOT prosthesis depth (β = 0.286, P = 0.009). Furthermore, ΔPR was associated with risk of PPMI (OR = 1.03, 95% CI 1.01-1.06, P = 0.024).nnnConclusionsnA low AVR is associated to higher ΔPR and PPMI rates. The correlation between LVOT prosthesis depth with ΔPR and higher PPMI rate suggests the need of a careful S3-THV implantation.