Treatment of amyloidosis: present and future.

Cardiac amyloidosis (CA) is an infiltrative heart disease resulting from the deposition of amyloid fibrils in the interstitial spaces of the myocardium. The two main forms of CA are represented by light chain amyloidosis (AL) and transthyretin amyloidosis (ATTR) in the two forms familial or variant or wild-type or senile. Although considered a rare disease, CA is an underdiagnosed disease. Delay in diagnosis has a negative impact on the prognosis, delaying the initiation of specific therapy. The treatment of both forms of CA is based on: (i) prevention and slowing of the generation and deposition of amyloid fibrils and (ii) supportive care of complications. The main success of recent years has been the development of effective therapies that have been possible thanks to the understanding of the pathophysiology of amyloidosis. For the AL form, new therapeutic combinations between a proteasome inhibitor and a monoclonal antibody have been developed. For ATTR forms, the main strategies are transthyretin (TTR) production 'silencers' and TTR tetramer stabilizers. Supportive care of patients with CA involves various clinical aspects including treatment of heart failure, arrhythmias, conduction disturbances, thrombo-embolism, and the concomitant presence of aortic stenosis.

A case of arrhythmogenic right ventricular cardiomyopathy with biventricular involvement.

We reported a case of a young adult male aged 18 years admitted in our institution for syncope during a basketball match. No previous symptoms were reported. Electrocardiogram (ECG) showed T-wave inversion in the anterior leads and an incomplete right bundle branch block. Surprisingly, a complete echocardiographic evaluation demonstrated the presence of severe right ventricular enlargement with significant wall motion abnormalities, apical aneurysm and reduced systolic function. Cardiac Magnetic Resonance was pathognomonic for a fibro-fatty replacement of both ventricles. We decided for a subcutaneous defibrillator implantation and, after inducing a ventricular fibrillation to test the device status, epsilon wave appeared on the ECG. This clinical scenario depicted an advanced arrhythmogenic right ventricular cardiomyopathy at its first clinical manifestation.

Secondary prevention and follow-up of patients with ACS and not-at-target LDL: An Italian real-world retro-prospective analysis by the inertia group.

Background: In patients with recent ACS, the latest ESC/EAS guidelines for management of dyslipidaemia recommend intensification of LDL-C-lowering therapy. Objective: Report a real-world picture of lipid-lowering therapy prescribed and cholesterol targets achieved in post-ACS patients before and after a specific educational program. Methods: Retrospective data collection prior to the educational course and prospective data collection after the course of consecutive very high-risk patients with ACS admitted in 2020 in 13 Italian cardiology departments, and with a non-target LDL-C level at discharge. Results: Data from 336 patients were included, 229 in the retrospective phase and 107 in the post-course prospective phase. At discharge, statins were prescribed in 98.1% of patients, alone in 62.3% of patients (65% of which at high doses) and in combination with ezetimibe in 35.8% of cases (52% at high doses). A significant reduction was obtained in total and LDL cholesterol (LDL-C) from discharge to the first control visit. Thirty-five percent of patients achieved a target LDL-C <55 mg/dL according to ESC 2019 guidelines. Fifty percent of patients achieved the <55 mg/dL target for LDL-C after a mean of 120 days from the ACS event. Conclusions: Our analysis, though numerically and methodologically limited, suggests that management of cholesterolaemia and achievement of LDL-C targets are largely suboptimal and need significant improvement to comply with the lipid-lowering guidelines for very high CV risk patients. Earlier high intensity statin combination therapy should be encouraged in patients with high residual risk.

Quantification of manual thrombus removal in patients with acute coronary syndromes: a study exploiting serial frequency domain-optical coherence tomography.

AIMS: Thrombus aspiration is useful in improving myocardial reperfusion in comparison to conventional percutaneous coronary intervention in patients with acute myocardial infarction. Nonetheless, assessment of thrombus aspiration efficacy is lacking. Aim of this study was to quantify by frequency domain optical coherence tomography (OCT) the amount of thrombus removal in patients with acute coronary syndromes undergoing manual thrombus aspiration, correlating it with the actual size of the retrieved material. METHODS: Twenty-five consecutive patients with acute coronary syndrome were enrolled. OCT assessment of thrombotic lesions was performed before and after thrombus aspiration and repeated after stent deployment. OCT thrombus assessment was based on an established scoring technique. The aspirated material was analyzed by histology, and its planimetry was correlated with OCT-derived thrombus removal. RESULTS: The percentage of thrombus removal [(prethrombus aspiration minus post-thrombus aspiration)/(prethrombus aspiration × 100)] was 48.9; the delta measurement of the removed thrombus calculated by OCT correlated well with the planimetry-measured aspirated material (r = 0.56, P < 0.01). CONCLUSION: The present study showed the following: the thrombus score derived by OCT measurements correlated reasonably well with the planimetry measure of surface area of the actual aspirated material; after thrombus aspiration a large amount of residual thrombus can be appreciated at the target lesion site; and tissue components such as cholesterol debris and inflammatory cells can often be retrieved during thrombus aspiration.

Optical coherence tomography guided in-stent thrombus removal in patients with acute coronary syndromes.

The persistence of thrombus inside stent struts is a frequent event in patients with acute coronary syndromes (ACS) undergoing percutaneous coronary intervention (PCI), and this phenomenon might be associated with an increased risk of stent thrombosis. We sought to quantify by means of optical coherence tomography (OCT) the presence of in-stent thrombus after achievement of an optimal angiographic result in patients with ACS undergoing PCI. In addition, we evaluated the feasibility and safety of an OCT-guided strategy of in-stent thrombus removal. Eighty consecutive patients with ACS undergoing PCI were treated with two different strategies equally divided into two groups: angio-guided PCI, and OCT-guided PCI, in which additional OCT-driven in-stent balloon dilatation was adopted to reduce thrombus encroachment of the lumen. Overall in-stent thrombus area was 4.3 % with a maximal thrombus encroachment of 16.7 %. In the OCT-guided group, use of high pressure intra-stent dilatation led to a significant increase in stented area (9.6 ± 2.4 vs. 9.1 ± 2.49 mm(2), p = 0.002) and lumen area (9.2 ± 2.4 vs. 8.7 ± 2.3 mm(2), p < 0.001) and also significantly decreased in-stent thrombus area in absolute (0.35 ± 0.29 vs. 0.42 ± 0.30 mm(2), p = 0.001) and relative terms (3.58 ± 3.25 vs. 4.53 ± 3.01 %, p = 0.001). Values of TIMI flow, frame count and blush grade, as well as clinical outcomes were not detrimentally affected by such additional dilatations. The use of additional OCT-driven in-stent balloon dilatations is feasible, safe and might be effective in the treatment of in-stent thrombus for patients with ACS.

Early vessel healing of the Avantgarde cobalt-chromium coronary stent: the ON-GARDE OCT study.

INTRODUCTION: Uncoverage and malapposition of stent struts at optical coherence tomography (OCT) have been associated with stent thrombosis. Stent uncoverage by OCT is being used as a surrogate to address the propensity of a stent to develop thrombosis. We aimed to appraise early vessel healing in patients with ST-elevation myocardial infarction (STEMI) treated with the novel Avantgarde stent. METHODS: Patients with STEMI and multivessel disease were enrolled. The stent deployed on the infarct-related artery was imaged by frequency domain-OCT during deferred intervention (4-7 days apart). The primary end-point was the percentage of uncovered struts. Secondary end-points were the percentage of malapposed struts and struts covered with thrombus. RESULTS: Twenty patients (20 lesions) were enrolled, with 18 (18 stents) achieving a complete OCT pull-back and thus entering the final analysis (1497 cross-sections, 11 446 struts). Uncovered struts were 3.9%, whilst 8.0% of struts were malapposed and 2.6% were covered by thrombus. At per-stent analysis, all stents but two had a homogeneous distribution of strut coverage (i.e. % of uncovered struts ≥10). CONCLUSIONS: This study, originally exploiting OCT data early after stenting in STEMI patients, shows that the Avantgarde stent is associated with favourable vessel healing features.

Integrated non-invasive imaging techniques.

The development of imaging techniques for the non-invasive detection of atherosclerosis answered the specific need of identifying vulnerable plaque in asymptomatic patients, verify the presence of atherosclerosis in patients at intermediate risk of coronary artery disease and, lastly, evaluate the results of previous coronary interventions. Coronary computed tomography angiography is the non-invasive technique that has been most widely used for these purposes. The technique mainly focuses on the presence of calcium in the walls of the coronary arteries. Whether or not coronary arterial calcification is part of the development of atherosclerosis, it occurs in small amounts in the early lesions and is found more frequently in advanced lesions and at an older age. Plaques rich in collagen and calcium, which can be depicted by coronary calcium scoring, are widely considered firm and stable, whereas soft atheromas containing a core of lipids and necrotic debris that are biologically "unstable" and therefore prone to rupture, cannot be visualised by calcium scoring or correctly assessed by coronary computed tomography angiography. In fact, the relation of arterial calcification to the probability of plaque rupture is unknown. There is no definite relationship between vulnerable plaque and coronary artery calcification in comparative studies with intravascular ultrasound. On the other hand, radiographically detected coronary artery calcium can provide an estimate of total coronary plaque burden but, due to arterial remodelling, calcium does not concentrate exclusively at sites with severe coronary artery stenoses. In any event, this technique has great potential for identification of atherosclerosis. A more established use of coronary computed tomography angiography is in the evaluation of patients after coronary interventions. The future also holds promise for imaging coronary artery atherosclerotic plaques using magnetic resonance. At the present time, the differentiation of coronary plaque components with magnetic resonance is limited by inadequate spatial resolution; however, promising research is ongoing and the role of magnetic resonance in the evaluation of patients with coronary artery disease will continue to grow as its utility and prognostic importance will be further defined.

Safety and feasibility of frequency domain optical coherence tomography to guide decision making in percutaneous coronary intervention.

AIMS: The purpose of this single centre registry is to assess safety and feasibility of the frequency domain optical coherence tomography (FD-OCT) system during coronary interventions. METHODS AND RESULTS: Ninety patients with unstable or stable coronary artery disease were included in this study. OCT imaging was performed in a first group of 40 patients (group 1), to evaluate ambiguous/intermediate lesions (24 patients in group 1 had OCT also done post-PCI, for assessment of stent deployment); and in a second group of 50 patients (group 2), to address the adequacy of stent deployment. Therefore, 74 patients underwent FD-OCT after stent implantation. A complex-lesion population was studied (B2 type lesion=72.2% and C type lesion=20.3%). The mean time of a FD-OCT pull-back (from the set up to the completion of the pull back) was 2.1 min and in all but one (99.1%) the procedure was successful. No patients experienced major complications in terms of death, myocardial infarction, emergency revascularisation, embolisation, life-threatening arrhythmia, coronary dissection, prolonged and severe vessel spasm and contrast induced nephropathy. In the ambiguous lesion group, 60% of patients were treated with PCI, whilst in the others, PCI were deferred. In total, 113 deployed stents (33,6% chromium cobalt stent, 66,4% drug eluting stent) were imaged with OCT. OCT findings led to additional interventions in 24 out of 74 patients (32%): 15 had further balloon inflations, nine had additional stent deployment whilst two had both treatments. At clinical follow-up, (4.6 ± 3.,2 months), there were no death, acute myocardial infarctions and cases of stent thrombosis, whilst two patients underwent revascularisation for recurrence of angina. CONCLUSIONS: The present registry shows that FD-OCT is a feasible and safe technique for guidance of coronary interventions. Randomised studies will confirm whether the use of FD-OCT will improve the clinical outcome.