We are surrounded by factors called free radicals (FR), which attach to the molecules our body is made of, first among them the endothelium. Even though FR are to a certain extent a normal factor, nowadays we face an escalating increase in these biologically aggressive molecules. The escalating formation of FR is linked to the increased usage of man-made chemicals for personal care (toothpaste, shampoo, bubble bath, etc.), domestic laundry and dish-washer detergents, and also an ever wider usage of drugs (both prescription and over the counter), especially if they are to be used long-term (years). In addition, tobacco smoking, processed foods, pesticides, various chronic infectious microbes, nutritional deficiencies, lack of sun exposure, and, finally, with a markedly increasing impact, electromagnetic pollution (a terribly destructive factor), can increase the risk of cancer, as well as endothelial dysfunction, owing to the increased production of FR that they cause. All these factors create endothelial damage, but the organism may be able to repair such damage thanks to the intervention of the immune system supported by antioxidants. However, one other factor can perpetuate the state of inflammation, namely obesity and metabolic syndrome with associated hyperinsulinemia. In this review, the role of FR, with a special emphasis on their origin, and of antioxidants, is explored from the perspective of their role in causing atherosclerosis, in particular at the coronary level.

Lead pacemaker infection is a complication on the rise. An infected oscillating mass attached to the leads (ILV) is a common finding in this setting. Percutaneous extraction of the leads and of the device is the best curative option. However, extraction of leads with large masses can be complicated by pulmonary embolism. The aim of this study was to understand the factors associated with large ILV using a sophisticated ultrasound technique to visualize the masses, namely intracardiac echocardiography (ICE), and investigate whether larger masses induce more complications during and after extraction. Percutaneous lead extraction and peri-procedural ICE were done in 36 patients (pts) (75 ± 11 years old, 74% males). Vegetations (max dimension = 8.2 ± 4.1 mm) in the right cavity were found in 26 of them, mostly adhering to the leads. We subdivided the patients into 2 groups: with vegetation size < 1 cm (18 pts) and vegetation size ≥ 1 cm (8 pts). By univariate analysis, we found that patients in group 1 were more often taking anticoagulation therapy (p = 0.03, Phi (Phi coefficient) = −0.5, OR [odds ratio] 0.071) and had signs of local pocket infection (p = 0.02, Phi = −0.52, OR 0.059) while significantly more patients in group 2 had diabetes (p = 0.08, Phi = 0.566, OR 15); moreover the patients in group 2 showed a trend toward a more frequent positive blood culture (p = 0.08, Phi = 0.39, OR 5.8) and infection with coagulase negative staphylococci (p = 0.06, Phi = 0.46, OR 8.3). At multivariate analysis, only 3 factors (diabetes, younger age and anticoagulation therapy) were independently associated with ILV size: diabetes, associated with larger vegetations (group 2), showed the largest beta value (0.44, p = 0.008); age was inversely correlated with ILV size (beta value = −32, p = 0.038), and anticoagulation therapy (beta value = −029, p = 0.048) was more commonly associated with smaller vegetations (group 1). Larger ILV were not associated with more complications or death during or after the extraction. Conclusion: diabetes, anticoagulation therapy and age are independent predictors of lead vegetation size. The embolic potential of large ILV during extraction was modest, so ILVs >1cm are not a contraindication to percutaneous extraction of infected leads.

The significance of the slow coronary flow phenomenon (SCFph), as visualized in patients (pts) with angiographically normal coronary arteries, is controversial. Absolute coronary flow reserve (CFR) in the left anterior descending coronary artery (LAD), non-invasively assessed by a transthoracic color-guided pulsed-wave Doppler (E-Doppler TTE), is a reliable parameter to assess coronary microcirculatory dysfunction (CMD). Mild and angiographically hidden epicardial atherosclerosis (Hath), as visualized by intracoronary ultrasound (IVUS), which could be the clue to atherosclerotic coronary microvascular involvement, has never been investigated together with CFR in patients. This study was aimed at assessing the value of CFR and HA in explaining the SCFph. Methods. Both non-invasive assessment of CFR in the LAD and corrected TIMI frame count assessment of the coronary contrast runoff were performed in 124 pts with angiographically normal coronary arteries. Among the whole group, 32 patients also underwent intracoronary ultrasounds in the LMCA and LAD, and the maximal plaque burden was assessed (Lesion external elastic (EEM) cross sectional area (CSA)—Lesion Lumen CSA/Lesion EEM CSA * 100). We found that 24 of the 124 pts (group 1) had the SCFph and the remaining 100 had a normal runoff (group 2). CFR, evaluated in both groups, was not significantly different, being 2.79 ± 0.79 (Mean ± SD) in group 1 and 2.90 ± 0.8 in group 2 (p = ns); in the pts also examined by IVUS (32 pts), the SCFph was always associated with hidden atherosclerosis, and a plaque burden of ≥33%. On the contrary, in the normal runoff group, any grade of PB was observed (from no athero to a PB > 70%) and remarkably, 10 pts had no signs of athero or just a minimal plaque burden. This resulted in a ROC curve analysis in which PB < 33% had a high negative predictive value (100%) in ruling out the SCFph. In addition, considering a CFR value < 2.21 as an index of coronary microcirculatory dysfunction, we found CMD in 15 pts (15%) in group 1 and in 7 pts (29%) in group 2 (p = ns). In conclusion, the SCFph is strongly connected to epicardial athero to the extent that the absence of hidden coronary athero has a very high negative predictive power in ruling out SCFph. CFR that is based on an endothelium-independent mechanism remains fairly normal in this condition. An endothelium-dependent microcirculatory constriction at rest due to atherosclerotic involvement of the coronary microvascular network is a possible explanation of the SCFph.

Background: A lead-reactive fibrous capsule (FC) identified by ultrasounds as an atrial or ventricular lead thickness of more than 1 mm above the vendor-declared lead diameter (TL) and its local fibrotic attachment to the cardiac wall (FAC) have never been investigated in vivo, so their relationship with post-extraction masses (ghost) is not known. Methods: Intracardiac echocardiography (ICE) was performed twice during the same extraction procedure in 40 consecutive patients: before and immediately after infected lead extraction Results: The ghost detection rate was high: 60% (24/40 patients); ICE could identify both TL and FAC, TL being noted in 25/40 (62%) patients and FAC in 12/40 patients (30%). Both TL and FAC were significantly associated with ghosts (p < 0.001 and p = 0.002, respectively), but TL had a higher prediction power. The specificity was similar: 94% (15/16) and 100% (16/16), respectively, but TL showed a much higher sensitivity: 100%, (24/24) vs 50% (12/24) (p = 0.016). The ghost group did not show a higher event rate in the follow-up (mean follow-up time = 20 ± 17 months). Conclusion: ICE is able to evaluate both TL and FAC in vivo; ghosts are mostly benign remnants of fibrotic lead capsule cut off during extraction and retained inside the heart by FAC.

We report the case of a 71-year-old patient with many risk factors for coronary atherosclerosis, who underwent computed coronary angiography (CTA), in accordance with the guidelines, for recent onset atypical chest pain. CTA revealed critical (>50% lumen diameter narrowing) stenosis of the proximal anterior descending coronary, and the patient was scheduled for invasive coronary angiography (ICA). Before ICA he underwent enhanced transthoracic echo-Doppler (E-Doppler TTE) for coronary flow detection by color-guided pulsed-wave Doppler recording of the left main (LMCA) and whole left anterior descending coronary artery (LAD,) along with coronary flow reserve (CFR) in the distal LAD calculated as the ratio, of peak flow velocity during i.v. adenosine (140 mcg/Kg/m) to resting flow velocity. E-Doppler TTE mapping revealed only mild stenosis (28% area narrowing) of the mid LAD and a CFR of 3.20, in perfect agreement with the color mapping showing no flow limiting stenosis in the LMCA and LAD. ICA revealed only a very mild stenosis in the mid LAD and mild atherosclerosis in the other coronaries (intimal irregularities). Thus, coronary stenosis was better predicted by E-Doppler TTE than by CTA. Coronary flow and reserve as assessed by E-Doppler TTE trumps coronary anatomy as assessed by CTA, without exposing the patient to harmful radiation and iodinated contrast medium.

Background: Coronary blood flow Doppler recording by Transthoracic Doppler in convergent mode (E-Doppler TTE) might be further improved by lowering heart rate (HRL) down to <60 bpm, since low HR < 60 b/m causes a disproportional lengthening of the diastole, so the coronaries are still for a longer time, very much improving the Doppler signal/noise ratio. Methods: A group of 26 patients underwent E-Doppler TTE before and after HR lowering in four branches of the coronary tree, namely, the left main (LMCA); left anterior descending (LAD), subdivided into three segments: proximal, mid and distal; proximal left circumflex (LCx); and obtuse marginal (OM). Color and PW coronary Doppler signal was judged by two expert observers as undetectable (SCORE 1), weak or with clutter artifacts (SCORE 2), or well delineated (SCORE 3). In addition, local accelerated stenotic flow (AsF) was measured in the LAD before and after HRL. Results: Beta-blockers significantly decreased the mean HR from 76 ± 5 to 57 ± 6 bpm (p < 0.001). Before HRL, the Doppler quality was very poor in the proximal and mid-LAD segments (median score value = 1 in both), while in the distal LAD, it was significantly better but still suboptimal (median score value = 1.5, p = 0.009 vs. proximal and mid-LAD score). After HRL, blood flow Doppler recording in the three LAD segments was strikingly improved (median score value = 3, 3 and 3, p = ns), so the effect of HRL was more efficacious in the two more proximal LAD segments. In 10 patients undergoing coronary angiography (CA), no AsF as expression of transtenotic velocity was detected at baseline. After HRL, thanks to the better quality and length of color flow, ASF was detected in five patients while in five others, it was not in perfect agreement with CA (Spearman correlation coefficient = 1, p < 0.01). The color flow in the proximal LCx and OM was extremely poor at baseline (color flow length 0 and 0, median (interquartile range) mm, respectively) and improved considerably after HRL (color flow length 23 [13.5] and 25 [12.0] mm, respectively, p < 0.001). Conclusions: HRL greatly improved the success rate of blood flow Doppler recording in coronaries, not only in the LAD, but also in the LCx. Therefore, AsF for stenosis detection and coronary flow reserve assessment can have wider clinical applications. However, further studies with larger samples are needed to confirm these results.