Massimo Fineschi

Assessment of vascular function: flow-mediated constriction complements the information of flow-mediated dilatation

Objective: To determine whether vascular function assessed by low-flow-mediated constriction (L-FMC), a novel non-invasive method, complements the information obtained with “traditional” flow-mediated dilatation (FMD). Design and patients: In protocol 1, 12 healthy young volunteers underwent FMD and L-FMC measurements at rest and immediately after isometric exercise of the same hand. In protocol 2, 24 patients with coronary artery disease, 24 with congestive heart failure, 24 hypertensive patients and 64 healthy volunteers were enrolled to undergo L-FMC and FMD measurements. Results: In protocol 1, exercise was associated with mean (SD) increases in radial artery blood flow, diameter and L-FMC (from −5.1 (1.5)% to −7.8 (3.4)%, p<0.05), while FMD was significantly blunted (from 6.0 (2.4)% to 3.0 (3.2)%, p<0.05). In protocol 2, both FMD and L-FMC were blunted in the patient groups. Receiver operating curve analysis showed that, as compared with FMD alone, the combination of L-FMC and FMD significantly improved the sensitivity and specificity in detecting patients diagnosed with cardiovascular disease (p<0.05). Conclusion: In the first protocol, FMD and L-FMC were shown to be reciprocally regulated. A blunted FMD may, in certain cases, be an expression of increased resting vascular activation and not only of impaired endothelial function. In the second protocol, a statistical approach showed that implementation of L-FMC provides a better characterisation than FMD of vascular function in cardiovascular disease. Vascular (endothelial) function is a complex phenomenon which requires a multifaceted approach; it is suggested that a combination of L-FMC and FMD will provide additive and complementary information to “traditional” FMD measurements.

Stent-related defects in patients presenting with stent thrombosis: differences at optical coherence tomography between subacute and late/very late thrombosis in the Mechanism Of Stent Thrombosis (MOST) study.

AIMS Subacute, late, and very late stent thrombosis (ST) may occur after stent implantation, but they are characterised by different underlying pathophysiological mechanisms. We sought to appraise differences between subacute and late/very late ST at the thrombus site by optical coherence tomography (OCT). The Mechanism Of Stent Thrombosis (MOST) study was a prospective multicentre non-randomised registry which enrolled six subacute ST and six controls (subacute ST study), and 17 late/very late ST and 17 controls (late/very late ST study). METHODS AND RESULTS Patients with subacute ST had a minimum stent area at the thrombus site of 2.1 mm² (1st-3rd quartile 1.3-4.5) vs. 2.9 mm² (2.4-5.0) in the matched control (p=0.05). Uncovered struts were 26.2% (16.5-35.9) vs. 13.9% (8.9-18.9), p=0.001. Malapposed struts were 18.8% (13.1-24.5) vs. 15.2% (12.8-17.6), p=0.001. In patients with late/very late ST, uncovered struts were 23.6% (13.9-33.3) vs. 5.2% (0.5-10.2), p=0.001. Malapposed struts were 12.1% (6.4-17.8) vs. 2.8% (0.4-5.2), p=0.001, and maximum malapposition distance was 0.45 mm (0.32-0.62) vs. 0.12 mm (0-0.25), p=0.01. Notably, all patients with ST had previously discontinued dual antiplatelet therapy (n=14) or showed high residual platelet reactivity on clopidogrel therapy. CONCLUSIONS Subacute ST had a significant stent underexpansion while late/very late ST had a greater stent strut malapposition distance at the thrombus site. These findings explain how procedure-related complications and vessel remodelling have a specific impact on the segment characterised by thrombus. High platelet reactivity also seems a necessary cofactor for both subacute and late/very late ST. CLINICAL TRIAL REGISTRATION http://www.clinicaltrials.gov unique identifier NCT01410539.

Bioresorbable Scaffold vs. Second Generation Drug Eluting Stent in Long Coronary Lesions requiring Overlap: A Propensity-Matched Comparison (the UNDERDOGS study).

BACKGROUND Randomized clinical trials on bioresorbable scaffolds (BRS) enrolled patients with simple coronary lesions. The present study was sought to give preliminary findings about safety of BRS implantation in overlap in long coronary lesions. METHODS From June 2012 to January 2015, we prospectively collected data from 162 consecutive patients receiving overlapping BRS implantation in the 16 participating institutions. We applied a propensity-score to match BRS-treated patients with 162 patients receiving second generation drug eluting stents (DES) in overlap. The primary endpoint was a device-oriented endpoint (DOCE), including cardiac death, target vessel myocardial infarction, and target lesion revascularization. RESULTS DOCE rate did not significantly differ between the two groups (5.6% in BRS group vs. 7.4% in DES group, HR 0.79, 95%CI 0.37-3.55, p=0.6). Also stent/scaffold thrombosis did not differ between groups (1.2% in BRS group vs. 1.9% in DES group, p=0.6). Occurrence of procedural-related myocardial injury was significantly higher in the BRS group (25% vs. 12%, p=0.001), although it was not related to DOCE (HR 1.1, 95%CI 0.97-1.2, p=0.2). Imaging techniques and enhanced stent visualization systems were significantly more employed in the BRS group (p=0.0001 for both). Procedure length, fluoroscopy time and contrast dye amount were significantly higher in the BRS group (p=0.001, p=0.001 and p=0.01, respectively). CONCLUSIONS Overlapping BRS utilization in long coronary lesions showed a comparable DOCE rate at 1year if compared to second generation DES. Further and larger studies are on demand to confirm our findings.

Long-Term Effectiveness and Safety of Sirolimus Stent Implantation for Coronary In-Stent Restenosis: Results of the TRUE (Tuscany Registry of Sirolimus for Unselected In-Stent Restenosis) Registry at 4 Years

OBJECTIVES The aim of this study was to evaluate the long-term clinical outcome of the efficacy and safety of sirolimus-eluting stents (SES) for in-stent restenosis (ISR) in the TRUE (Tuscany Registry of Unselected In-Stent Restenosis) database. BACKGROUND The TRUE registry demonstrated that SES in the treatment of bare-metal stent ISR is efficacious (5% of target lesion revascularization [TLR]) and safe (stent thrombosis <1%) at 9 months. Clinical outcome at 4 years is reported. METHODS A total of 244 patients with ISR who were treated with SES implantation represent the study population. The incidence of major adverse cardiac events was collected at 4 years. RESULTS At 4-year follow-up, overall mortality was 9.8% (24 patients). Cardiac death occurred in 11 (4.5%), nonfatal myocardial infarction in 8 (3.2%), and TLR in 27 (11.1%) patients for a cumulative event-free survival rate of 80.3%. Definite stent thrombosis occurred in 5 (2%) patients and possible stent thrombosis in 2 (0.8%). Diabetes remained an independent negative predictor of freedom from TLR (odds ratio [OR]: 0.38; 95% confidence interval [CI]: 0.20 to 0.71, p = 0.002) and major adverse cardiac events (OR: 0.38; 95% CI: 0.20 to 0.71, p = 0.002). CONCLUSIONS The clinical benefit of SES implantation for bare-metal stent ISR is maintained at 4 years with a low TLR rate and an overall incidence of stent thrombosis of 0.7% per year.

The coronary slow flow phenomenon: a new cardiac "Y" syndrome?

The coronary slow flow phenomenon (CSFP) is an angiographic finding that is characterised by delayed progression of the contrast medium during coronary angiography. The mechanism of this phenomenon remains unknown. In the present paper, we revise the current evidence regarding this phenomenon and discuss recent findings from our group reporting increased resting resistances in patients with the CSFP. We report that these patients had preserved blood flow responses to the intracoronary infusion of the vasodilator papaverine, demonstrating that the CSFP is not necessarily associated with an abnormal coronary flow reserve. Based on these findings and on the review of the current literature, we concur with the concept proposed by Beltrame et al. that the CSFP should be considered a separate clinical entity. Further studies are necessary to describe the clinical characteristics, including the prognosis, of these patients and to identify potential treatments.

The impact of gender on fractional flow reserve measurements.

AIMS Fractional flow reserve (FFR) allows accurate investigation of the functional significance of intermediate coronary stenoses. The present study set out to study the impact of gender on FFR measurements. METHODS AND RESULTS Three hundred and seventeen intermediate (40-70% at angiography) stenoses were assessed with FFR in 270 patients (mean age 65.8 ± 10.3 years, 84 females). Resting Pd/Pa (the ratio of mean blood pressure measured distal to the stenosis to mean aortic blood pressure in resting conditions), FFR (Pd/Pa during adenosine-induced hyperaemia) and the ΔPd/Pa (calculated as the change in Pd/Pa during hyperaemia) were measured. There was no difference in the location and degree of stenoses between genders (p>0.5). Similarly, there was no difference in age and in the prevalence of cardiovascular risk factors (all p>0.2). Resting Pd/Pa also did not differ between genders (0.92 ± 0.08 vs. 0.93 ± 0.05, p=0.23). In response to adenosine, however, a significantly larger ΔPd/Pa (0.14 ± 0.07 vs. 0.11 ± 0.07, p=0.001) and a significantly lower FFR (0.79 ± 0.12 vs. 0.82 ± 0.10, p=0.008) were observed in males. This difference was maintained in a multivariate regression analysis. CONCLUSIONS We observed gender-based differences in FFR data in daily routine. Further studies are necessary to test the mechanism of this observation and how these differences impact on the assessment of haemodynamically relevant stenoses.

Coronary slow flow: Description of a new “cardiac Y” syndrome

Angina in the presence of intact coronary arteries remains a relatively frequent clinical issue. It is now well understood that an impaired capacity to modulate coronary vascular resistances upon exercise (i.e. an impaired coronary flow reserve) may lead to ischemia and angina. We describe a case of coronary slow flow, i.e. a condition in which resting (micro) vascular resistances are inappropriately high, causing unstable angina. We propose that this novel syndrome should be called coronary syndrome Y to distinguish it from the better understood coronary syndrome X.

Two Coronary "Orphan" Diseases in Search of Clinical Consideration: Coronary Syndromes X and Y

We set out to describe the clinical characteristics of patients presenting with acute or stable coronary syndromes and no stenosis in epicardial coronaries. Although the existence of patients who experience typical angina and who have intact epicardial coronaries is well accepted, the pathophysiology of cardiac ischemia in this setting remains poorly understood. In typical coronary syndrome X, it is believed that at least two components play a role: the first is the incapacity of coronary resistance vessels to adapt to situations of increased blood demand, resulting in demand ischemia; the second is an inappropriate transduction or generation or pain stimuli within the central nervous system. These two mechanisms concur to determine episodes of precordial pain and electrocardiogram (ECG) evidence of ischemia during exercise. In contrast, the coronary slow-flow phenomenon, or syndrome Y, is an angiographic finding that is characterized by delayed progression of the contrast medium during coronary angiography. Although the mechanism of this phenomenon remains largely unknown, it has been proposed that it might depend on the presence of inappropriately high resting coronary resistances, causing reduced blood flow and therefore low-flow ischemia and unstable angina. Importantly, the prognosis of many of the patients presenting with coronary slow-flow does not appear to be favorable, with recurrence of acute coronary syndromes and life-threatening arrhythmias. In the present article, we revise the current evidence regarding these two phenomena, and propose that syndrome Y should be considered a separate clinical entity.

Atheromatous degeneration of the neointima in a bare metal stent: intravascular ultrasound evidence.

We report intravascular ultrasound evidence of a ruptured plaque within a bare metal stent restenosis. In the traditional view, in-stent restenosis is considered to be a benign condition associated with progressive apposition of inert extracellular matrix. The clinical correlate of this pathology would be stable angina. In contrast, recent data have shown that at least one-third of patients with in-stent restenosis present with acute coronary syndromes. This case provides in-vivo evidence that the neointima can undergo atheromatous degeneration and rupture. This matches evidence from recent registries and in-vitro data suggesting that bare metal stent restenosis should not be considered a clinically benign entity.

Polytetrafluoroethylene (PTFE) covered stents for the treatment of coronary artery aneurysms.

Coronary artery aneurysms are rare disorders defined by a vessel diameter > 1.5 times the reference artery. Aneurysms can be characterised by abnormal dilatation of a localised or diffuse arterial segment. Potential complications associated with these abnormalities include thrombus formation and distal embolisation and, rarely, rupture. Until recently, the only alternative to medical treatment was surgical ligation of the aneurysm with distal bypass surgery. …