Release of MMP-2 in the circulation of patients with acute coronary syndromes undergoing percutaneous coronary intervention: Role of platelets.

INTRODUCTION: Matrix metalloproteinases (MMPs) of atherosclerotic tissue contribute to plaque rupture triggering acute coronary syndromes (ACS). Several MMPs, including MMP-2, are also contained in platelets and released upon activation. An increase in circulating levels of MMP-2 has been reported in patients undergoing percutaneous coronary interventions (PCI), but its time-course and origin remain unclear. Aims of our study were to assess the time-course of MMP-2 release in blood of stable and unstable coronary artery disease patients undergoing PCI and to unravel the possible contribution of platelets to its release. METHODS: Peripheral blood samples were drawn immediately before, 4 and 24 h after PCI from patients with ACS (NSTEMI or STEMI, n = 21) or with stable angina (SA, n = 21). Platelet-poor plasma and washed platelet lysates were prepared and stored for subsequent assay of MMP-2 and ß-thromboglobulin (ß-TG), a platelet-specific protein released upon activation. RESULTS: Plasma MMP-2 and ß-TG increased significantly 4 h after PCI and returned to baseline at 24 h in ACS patients, while they did not change in SA patients. Platelet content of MMP-2 and ß-TG decreased significantly 4 h after PCI in patients with ACS, compatible with intravascular platelet activation and release, while they did not change in patients with SA. CONCLUSIONS: PCI triggers the release of MMP-2 in the circulation of ACS patients but not in that of patients with SA. Platelets activated by PCI contribute to the increase of plasma MMP-2 releasing their MMP-2 content. Given that previous mechanicistic studies have shown that MMP-2 may sustain platelet activation and unstabilize downstream-located plaques and in the long term favour restenosis and atherosclerosis progression, these data may encourage the search for therapeutic agents blocking MMP-2 release or activity in ACS.

Cytomegalovirus myocarditis in a patient with systemic lupus erythematosus (SLE) successfully treated with ganciclovir.

Myocarditis is an inflammatory disease of the myocardium. Viruses, such as enterovirus, adenovirus, parvovirus B19, HHV6 or cytomegalovirus (CMV) and autoimmune diseases are recognized causes of myocarditis. We describe the clinical case of a young Indian woman with SLE and a concomitant acute CMV related myocarditis with favourable outcome after ganciclovir therapy. CMV myocarditis may range from being a subclinical infection with incidental findings on ECG to a life threating presentation. There are no trials demonstrating the efficacy of antiviral therapy in myocarditis. Case series of patients with CMV myocarditis have reported an excellent clinical outcome after antiviral agents. Lupus Myocarditis (LM) is more prevalent in young females. There are no specific ECG or echocardiographic signs. Treatment strategies of LM are based on corticosteroids, immunosuppressive agents and cardiovascular support, usually with a favorable prognosis, but LM often lead to a severe clinical picture, with mortality of 10.3%. Endomyocardial biopsy (EBM) is recommended as the gold standard but it is very underused in clinical practice, It should be performed in a specialized center but there are concerns on lack of specificity, low negative predictive value, risk of complication, and sampling errors due to the focal nature of myocarditis. Both SLE and CMV are potentially responsible of acute myocarditis. In our knowledge, CMV myocarditis with SLE was described in only one other patient. The initiation of antiviral therapy improved the clinical picture and, in our opinion, it is mandatory when CMV related life threating conditions develop.

How to Measure 24-hour Central Blood Pressure and Its Potential Clinical Implications.

The evaluation of 24-hour central blood pressure (24h cBP) combines the cBP non-invasive assessment with the 24-h ambulatory BP measurement. The major strength of the 24-h cBP evaluation is the ability to assess the degree of circadian changes between central and peripheral BP, namely 24-h BP amplification. This allows an accurate quantification of the degree of spatial and temporal BP variability in each single individual. BP amplification depends from a number of factors, such as the interaction between pressure and flow pulsatile motions, vasomotor tone, arterial tapering and other physiological and anthropometrical determinants. The assessment of 24-h BP amplification, a relatively pressure-independent parameter, may be helpful in better refining the risk of organ damage and future CV events over traditional measures of office and 24-h brachial BP. Currently, only few devices enable the assessment of 24-h cBP. These devices are based on peripheral (brachial or radial) BP waveform detection, and reconstruction of central BP waveform through mathematical models. The estimation of 24-h cBP imputed from multivariate regression equations was also proposed. Clinical data are still scarce and, although suggesting a possible superiority of 24-h cBP over brachial BP in the association with markers of organ damage, they are limited by methodological and technical aspects. There is urgent need of a standardized methodology and rigorous validation protocols for the 24-h cBP assessment. The field of 24-h cBP measurement still requires significant advancements of scientific knowledge before its introduction into clinical practice.

Renal denervation for resistant hypertension: yes.

Sympathetic overactivity may have a role in triggering and maintaining resistant hypertension, and catheter-based renal denervation (RDN) has emerged as a promising treatment in refractory hypertension. Recently, the results of the Symplicity HTN-3, the first randomized, sham-controlled trial, failed to confirm the previously reported BP-lowering effects of RDN, although definitive conclusions cannot be drawn due to a number of study limitations. Consequently, although some centers halted their RDN programs, research continues and both the concept of denervation and treatment strategies are being redefined. A new generation of sham-controlled trials is currently underway with the aim of detecting which patients are expected to achieve the most beneficial effect from RDN. In this article, we examine the current data on RDN and discuss some insights and future opportunities.

Effectiveness of a novel biodegradable polymer, sirolimus-eluting stent platform in percutaneous coronary intervention.

BACKGROUND: The purpose of this registry is to report the immediate and long-term safety and efficacy of the Biotronik Orsiro stent in an unselected population during everyday practice. METHODS: Between May 2012 and June 2013, 246 consecutive coronary angioplasty procedures were performed using at least one Orsiro drug-eluting stent, in 225 patients and 303 lesions. RESULTS: Diabetes was present in 34.7% of patients. Procedures were non-elective percutaneous coronary intervention (PCI) in 17.1% of cases and acute coronary syndromes were 55.1%. Radial vascular access was used in 78% of cases, multivessel PCI was performed in 19.5% of the procedures. In 81.6% of cases lesions were B2/C type, 20.7% of procedures had bifurcation lesions. Procedural success was 99.6%. No acute thrombosis occurred. Clinical follow-up median period was 24.3 (±8.28) months and FU was available in 93.7% of patients. Death for any cause occurred in 11 patients (5.2%), 6 of them were non cardiac-related. Cardiac-related death rate was 2.4%. Two patients had in-stent restenosis. The overall target lesion failure rate was 3.3%. CONCLUSIONS: This observational data regards our experience with Biotronik Orsiro stent in an unselected population. This initial data, although limited by a mainly clinical follow-up and restricted number of patients, confirms the good clinical performance of this sirolimus-eluting stent with a biodegradable polymer in everyday practice, including complex lesions, according to current larger studies in the literature.

Bridge therapy or standard treatment for urgent surgery after coronary stent implantation: Analysis of 314 patients.

Intravenous administration of a short acting glycoprotein IIb/IIIa inhibitor has been proposed as a bridge to surgery in patients on dual antiplatelet treatment, but data in comparison with other treatment options are not available. We conducted a retrospective analysis of consecutive patients who underwent un-deferrable, non-emergency surgery after coronary stenting. The bridge therapy was performed after discontinuation of the oral P2Y12 inhibitor by using i.v. tirofiban infusion. Net Adverse Clinical Events (NACE) was the primary outcome. We analyzed 314 consecutive patients: the bridge strategy was performed in 87 patients, whereas 227 were treated with other treatment options and represent the control group. Thirty-day NACE occurred in 8% of patients in the bridge group and in 22.5% in the control group (p < 0.01). Bridge therapy was associated with decreased 30-day NACE rate [Odds ratio (OR) 0.30; 95% confidence interval (CI) 0.13-0.39; p < 0.01], particularly when the time interval between stenting and surgery was ≤ 60 days (OR 0.09, 95% CI 0.01-0.72; p = 0.02). There were no cases of stent thrombosis in the bridge group and 3 (1.3%) in the control group. Bridge therapy was associated with decreased events rates as compared to both patients with and without P2Y12 inhibitors discontinuation in the control group. After adjustment for the most relevant covariates, the favorable effect of the bridge therapy was not materially modified. In conclusion, perioperative bridge therapy using tirofiban was associated with reduced 30-day NACE rate, particularly when surgery was performed within 60 days after stent implantation.

Time course changes of cystatin C and inflammatory and biochemical markers in non-ST-elevation acute coronary syndromes.

BACKGROUND: Serum cystatin C (Cys-C), a good marker of renal function, predicts prognosis in non-ST-elevation acute coronary syndromes (NSTE-ACS). However, no data are available on the time course of Cys-C values after discharge. In this study, Cys-C was measured during admission (ACS sample) and 6 weeks after discharge, and was correlated with troponin (c-TNT), high-sensitivity C-reactive protein (hsCRP), interleukin 6 (IL-6) and the N-terminal portion of the pro-brain natriuretic peptide (proBNP) peptide (NT-proBNP) in a highly selected homogeneous group of NSTE-ACS patients. METHODS: In this prospective, multicentre study, patients with a first NSTE-ACS, single-vessel disease and successful percutaneous coronary interventions (PCIs) had their sera collected, aliquoted and stored at the enrolling site and then shipped for analysis to the clinical chemistry core laboratory. RESULTS: Cys-C values slightly, but significantly, increased from the ACS samples to the 6-week samples. In contrast, hsCRP, NT-proBNP and IL-6 values significantly decreased from the ACS to the 6-week sample. Patients with elevated c-TNT levels had higher hsCRP, NT-proBNP and IL-6 values than patients with normal c-TNT levels in the ACS sample, whereas Cys-C levels were similar in patients with and without elevated c-TNT. Cys-C was highly correlated with estimated glomerular filtration rate in both the ACS and 6-week samples. CONCLUSIONS: In contrast to inflammatory and biochemical stress markers, Cys-C is not affected by the occurrence of myocardial necrosis or by acute left-ventricular impairment, being a reliable marker of renal function during NSTE-ACS.

A giant coronary artery aneurysm with coronary arteriovenous fistula in asymptomatic elderly patient.

Coronary Arteriovenous Fistula (CAF) is a rare defect that occurs in 0.1-0.2% of patients undergoing coronary angiography; Coronary Artery Aneurism (CAA) also occurs in approximately 15-19% of patients with CAF. It is usually congenital, but in rare occasions it occurs after chest trauma, cardiac surgery, or coronary interventions. The case described is that of a 72-year-old woman, without previous history of cardiovascular disease, who presented a huge cardiac mass. A multimodal approach was necessary to diagnose a giant CAA with CAF responsible for compression and displacement of cardiac structures. Due to likely congenitally origin of the lesion and the absence of symptoms correlated to the CAA and to the CAF we decided to avoid invasive interventions and to treat the patient with medical therapy.

Operator exposure to x-ray in left and right radial access during percutaneous coronary procedures: OPERA randomised study.

OBJECTIVE: Left radial access (LRA) and right radial access (RRA) have been shown to be safe and effective for coronary arteries catheterisation. However, the differences between the two approaches in terms of radiation exposure are still unclear. The aim of the present investigation is to evaluate in a randomised study, the dose of radiation absorbed by operators using either LRA or RRA. DESIGN: Randomised, prospective, double arm, single centre study. SETTING: University Hospital. PATIENTS: Male or female subjects with stable, unstable angina and silent ischaemia. INTERVENTIONS: The present study is a comparison of LRA and RRA for coronary artery catheterisation in terms of operators' radiation exposure. MAIN OUTCOME MEASURES: The primary outcome measure was the radiation dose absorbed by operators; secondary outcome measures were fluoroscopy time, dose-area product and contrast delivered. RESULTS: A total of 413 patients were enrolled; 209 were randomly selected to undergo diagnostic procedures with RRA and 204 with LRA. The operator's radiation exposure was significantly lower in the left radial group (LRA 33±37 µSv vs RRA 44±32 µSv, p=0.04). No significant differences were observed in  fluoroscopy time (LRA 349±231s vs RRA 370±246 s p=0.09) and dose-area product (LRA 7011.42±3617.30 µGym(2) vs RRA 7382.38±5226.61 µGym(2), p=0.80), even though in both there was a trend towards a lower level in the LRA. No differences were observed in contrast medium delivered (LRA 89.92±32.55 ml vs RRA 88.88±35.35 ml, p=0.45). CONCLUSIONS: The LRA was associated in the present report with a lower radiation dose absorbed by the operator during coronary angiography.

Idiopathic, serial coronary vessels dissection in a young woman with psychological stress: a case report and review of the literature.

Spontaneous coronary artery dissection (SCAD) is a very rare disease, associated with high mortality rate, whose etiology and pathogenesis are poorly understood. Its sporadic nature and the varied angiographic extent make firm recommendations regarding revascularization impossible. The case described is that of a young, otherwise healthy woman, without a known underlying condition which may lead to SCAD, but with a history of intense psychological stress. We managed the patient with a conservative approach based on watchful waiting, medical therapy, and plain old balloon angioplasty (POBA) with low inflation atmospheres.

Left radial versus right radial approach for coronary artery catheterization: a prospective comparison.

BACKGROUND: Despite several advantages of the transradial over the transfemoral approach, the use of transradial access for coronary interventions in daily practice is still low. Major limitations are the technical and anatomical issues related with right radial artery access. The left radial approach may have an advantage from the point of view of the vascular anatomy. The aim of this study was to evaluate the safety and feasibility of routinely using the left radial compared to the right radial approach. METHODS: This is a prospective single center study comparing left radial to right radial access for coronary artery catheterization. The overall in-hospital major adverse cardiac and cerebral events (MACCE), procedural success rate, bleeding, vascular and procedural complications, fluoroscopy time, number of catheters, and amount of contrast agent used were assessed. RESULTS: A total of 1,032 coronary angiograms were performed: 420 were performed using the right radial artery and 612 the left radial artery. No differences were observed in MACCE and success rate between the two groups. No cases of major or minor bleeding and vascular complications requiring surgical intervention were reported. Fluoroscopy time and the number of catheters used were significantly less in the left radial group (P = 0.001 and P = 0.007, respectively), while the volume of contrast was similar (P = 0.264). CONCLUSIONS: The left radial approach in our series was demonstrated to be safe and feasible in daily practice, and in this study was associated with a reduction in fluoroscopy time and number of catheters used.

Impact of primary PCI volume on hospital mortality in STEMI patients: does time-to-presentation matter?

The exact relationship between primary percutaneous coronary intervention (PCI) volume and mortality remains unclear. No data are available on how this relationship could be affected by time-to-presentation. The primary aim of this study was to evaluate the impact of hospital primary PCI volume on in-hospital mortality in ST-elevation myocardial infarction (STEMI) patients depending on time-to-presentation. The impact of primary PCI volume on in-hospital mortality was investigated in a prospective registry of the Lombardy region in Northern Italy, deriving data on mortality rates and number of primary PCIs from a cohort of 2,558 patients. We also explored this relationship at different times-to-presentation (≤90 min, >90 min-180 min, >180 min) and risk profiles assessed with the TIMI Risk Index. A strong inverse relationship was found between primary PCI hospital volume and risk-adjusted mortality (r = -0.9; P < 0.001). High primary PCI volumes best predicted the improvement of survival when the time-to-presentation was ≤90 min (area under the curve = 0.73, P < 0.0001). At this time, the best primary PCI threshold to provide benefit was >66 primary PCIs/year (OR = 0.21 [95% CI 0.10-0.47], P < 0.001) and those with high TIMI Risk Index achieved the greatest benefit (P < 0.001). At >90 min-180 min, the model was less significant (P = 0.02) with a higher threshold of procedures (>145 primary PCIs/year) required to provide benefits. The model was not predictive of survival for time-to-presentation >180 min (P = 0.30). The reduction of mortality of STEMI patients treated at high-volume primary PCI centers is time-dependent and affected by risk profile. The greatest benefit was observed in high-risk patients presenting within 90 min from symptoms onset.

Importance and limits of pre-hospital electrocardiogram in patients with ST elevation myocardial infarction undergoing percutaneous coronary angioplasty.

BACKGROUND: The purpose of this study is to present data on the effects of pre-hospital electrocardiogram (PH-ECG) on the outcome of ST elevation myocardial infarction (STEMI) patients treated with percutaneous coronary angioplasty (PCI) included in a registry undertaken in the Italian region of Lombardy. Pre-hospital 12-lead electrocardiogram is recommended by current guidelines in order to achieve faster times to reperfusion in patients with STEMI. METHODS: The registry includes 3901 STEMI patients who underwent primary PCI over an 18-month period. RESULTS: Mean age was 63 ± 12 years. Admission through the emergency medical system (EMS) occurred in 1603 patients (40%): they were older, more frequently had previous MI, TIMI flow = 0 at entry and were more frequently in Killip class >1 than patients who were not admitted through the EMS. Among the patients admitted through the EMS, PH-ECG was obtained in 475 patients (12%). These patients had less frequently an anterior MI, but more frequently had absence of TIMI flow at entry than patients whose ECG was not teletransmitted. Moreover, they had a significantly shorter first medical contact-to-balloon time and a trend toward a lower 30-day death rate (5.3% vs 7.9 %, p = 0.06). However, only patients in Killip class 2-3 had a significantly lower mortality when the diagnostic ECG was transmitted, whereas no difference was found in Killip class 1 or Killip class 4 patients. CONCLUSIONS: In this registry, PH-ECG significantly decreased first medical contact-to-balloon time. Attempts to achieve faster reperfusion times should be undertaken, as this may result in improved outcome, particularly in patients with mild to moderate symptoms of heart failure.

Platelets release active matrix metalloproteinase-2 in vivo in humans at a site of vascular injury: lack of inhibition by aspirin.

When stimulated in vitro, human platelets release matrix metalloproteinase-2 (MMP-2) that, in turn, potentiates platelet activation. The present study investigated if MMP-2 is released from activated platelets in vivo in humans and whether aspirin inhibits this release. MMP-2 levels were measured by zymography, immunoblotting, flow-cytometry and an activity assay system, in plasma prepared from blood emerging from a skin wound inflicted for the measurement of the bleeding time (shed blood) and simultaneously from venous blood in 27 healthy human volunteers. In a subgroup, the same measurements were carried out before and 1 h after aspirin intake. MMP-2 was significantly higher in shed blood than in venous blood and increased progressively, consistent with ongoing platelet activation. A significant correlation was evident between platelet number and MMP-2 in shed blood; platelet MMP-2 content in shed blood was lower than that of platelets in venous blood. The level of active MMP-2 released by activated platelets in vivo was within the range of concentrations that potentiate platelet activation. Aspirin did not reduce MMP-2 release in vivo. In conclusion, MMP-2 is released from platelets in vivo in humans at a localised site of vessel wall damage in amounts sufficient to potentiate platelet aggregation; aspirin does not reduce this release.