Efficacy and safety of glucagon-like peptide-1 agonists on macrovascular and microvascular events in type 2 diabetes mellitus: A meta-analysis.

AIMS: Glucagon-like peptide-1 (GLP-1) agonists improve glycaemic control in type 2 diabetes mellitus (DM). Outcome trials investigating macro and microvascular effects of GLP-1 agonists reported conflicting results. The aim of this study was to assess, in a meta-analysis, the effects of GLP-1 agonists on mortality, major nonfatal cardiovascular (CV) events, renal and retinal events. DATA SYNTHESIS: MEDLINE, Cochrane, ISI Web of Science, SCOPUS and ClinicalTrial.gov databases were searched for articles published until June 2017. Randomized trials enrolling more than 200 patients, comparing GLP-1 versus placebo or active treatments in patients with DM, and assessing outcomes among all-cause death, CV death, MI, stroke, HF, diabetic retinopathy and nephropathy were included. 77 randomized trials enrolling 60,434 patients were included. Compared to control, treatment with GLP-1 significantly reduced the risk of all-cause death (RR: 0.888; CI: 0.804-0.979; p = 0.018) and the risk of CV death (RR: 0.858; CI: 0.757-0.973; p = 0.017). GLP-1 agonists did not affect the risk of MI (RR: 0.917; CI: 0.830-1.014; p = 0.092) as well as the risk of stroke (RR: 0.882; CI: 0.759-1.023; p = 0.097), HF (RR: 0.967; CI: 0.803-1.165; p = 0.725), retinopathy (RR: 1.000; CI: 0.807-1.238; p = 0.997) and nephropathy (RR: 0.866; CI: 0.625-1.199; p = 0.385). CONCLUSIONS: Treatment with GLP-1 agonists in DM patients is associated with a significant reduction of all cause and CV mortality.

Vitamin D deficiency and clinical outcome in patients with chronic heart failure: A review.

AIM: The aim of this review was to summarize evidence on the role of Vitamin D deficiency in heart failure (HF), from pathophysiological mechanisms to clinical effects of Vitamin D supplementation. DATA SYNTHESIS: Chronic HF secondary to left ventricular (LV) systolic dysfunction is a growing health problem, still associated with poor clinical outcome. In recent years, experimental and epidemiological evidence focused on the role of Vitamin D in HF. Cross sectional studies demonstrated that prevalence of HF is increased in patients with Vitamin D deficiency or parathyroid hormone (PTH) plasma level increase, whereas longitudinal studies showed enhanced risk of developing new HF in patients with Vitamin D deficiency. In addition, in patients with established HF, low plasma levels of Vitamin D are associated with worsening clinical outcome. Yet, clinical studies did not definitively demonstrate a benefit of Vitamin D supplementation for preventing HF or ameliorating clinical outcome in patients with established HF. CONCLUSIONS: Despite convincing experimental and epidemiological data, treatment with Vitamin D supplementation did not show clear evidence of benefit for preventing HF or influencing its clinical course. Ongoing clinical studies will hopefully shed lights on the effects of Vitamin D supplementation on clinical endpoints along the spectrum of HF.

Cutting balloon angioplasty for the treatment of in-stent restenosis: a matched comparison with rotational atherectomy, additional stent implantation and balloon angioplasty.

OBJECTIVES: The purpose of the study was to determine whether cutting balloon angioplasty (CBA) has advantages over other modalities in treatment of in-stent restenosis (ISR). BACKGROUND: Controversies exist regarding optimal treatment for ISR. Recently, CBA emerged as a tool in management of ISR. METHODS: A total of 648 lesions treated for ISR were divided into four groups according to the treatment strategy: CBA, rotational atherectomy (ROTA), additional stenting (STENT), and percutaneous transluminal coronary angioplasty (PTCA). Following the matching process, 258 lesions were entered into the analysis. RESULTS: Baseline clinical and angiographic characteristics were similar among the groups (p = NS). Acute lumen gain was significantly higher in the STENT group (2.12 +/- 0.7 mm), whereas in the CBA group the gain was similar to one achieved following ROTA and following PTCA (1.70 +/- 0.6 vs. 1.79 +/- 0.5 mm and 1.56 +/- 0.7 mm, respectively; p = NS). The lumen loss at follow-up was lower for the CBA versus ROTA and versus STENT (0.63 +/- 0.6 vs. 1.30 +/- 0.8 mm and 1.36 +/- 0.8 mm, respectively; p < 0.0001), yielding a lower recurrent restenosis rate (20% vs. 35.9% and 41.4%, respectively; p < 0.05). By multivariate analysis, CBA (odds ratio [OR] = 0.17; confidence interval [CI], 0.06 to 0.51; p = 0.001) and diffuse restenosis type at baseline (OR = 2.07; CI, 1.15 to 3.71; p = 0.02) were identified as predictors of target lesion revascularization. CONCLUSIONS: We conclude that CBA is a safe and efficient technique for treatment of ISR, with immediate results similar to atheroablation and better clinical and angiographic outcomes at follow-up. This approach might be implemented as a viable option in management of focal ISR and to prepare diffuse ISR for brachytherapy treatment.

Reduction of isoflurane MAC with buprenorphine and morphine in rats.

Preoperative analgesics are being increasingly used to provide analgesia in the intraoperative and postoperative period. Opioids reduce anaesthetic requirements, although the effect varies with the different drug and species. The aim of this work was to determine whether buprenorphine reduces the minimum alveolar concentration (MAC) of isoflurane in a dose-related fashion, and whether this effect is similar to morphine when clinical doses of both drugs are used in the rat. Thirty-six male Wistar rats were anaesthetized with isoflurane, and MAC was determined before and after the administration of either buprenorphine or morphine. MAC of isoflurane was determined from alveolar gas samples when a standard noxious stimulus, in the form of a tail clamp, was applied. The duration and degree of reduction of the MAC of isoflurane were recorded. Basic cardiovascular and respiratory measurements were also recorded. Buprenorphine (10, 30 and 100 microg/kg) and morphine (1, 3 and 10 mg/kg) reduced in a dose-dependent fashion the MAC of isoflurane by 15%, 30% and 50%, respectively. Buprenorphine resulted in less cardiovascular and respiratory depression and had a longer-lasting action than morphine. In conclusion, buprenorphine has a dose-related isoflurane sparing effect in the rat similar to that caused by morphine at clinical doses of both drugs.

Predictors of long-term clinical outcome in patients undergoing multiple vessel stenting for coronary artery disease.

BACKGROUND: Coronary artery stenting reduces the restenosis rate compared to coronary angioplasty alone. With the increased number of procedures completed with stent placement there has been a parallel increase in the number of procedures performed in patients with multivessel disease and therefore a rise in the number of patients receiving multiple stents. The clinical outcome and the predictors of the outcome of patients receiving multiple stents are not known. METHODS: To evaluate the clinical outcome of patients with multivessel coronary artery disease undergoing multiple stenting we studied 133 consecutive patients who had received > 1 stent in at least two vessels. A total of 375 coronary stents (2.8 stent per patient) were implanted in elective procedure situations. Clinical follow-up was complete in 100%. RESULTS: During follow-up 2 patients (1.5%) died (1 cardiac death), 4 patients (3%) had acute myocardial infarction, 96 patients (72.1%) remained angina-free, and 31 patients (23.3 %) had recurrence of angina. Repeat revascularization procedure was performed in 45 patients (33.8%); 43 patients (32.3%) underwent coronary angioplasty; 2 patients (1.5%) underwent coronary artery bypass grafting. The female gender and the presence of diabetes were significant (p < 0.05) predictors for coronary angioplasty or coronary artery bypass grafting procedures during follow-up. Recurrence of angina was also significantly (p < 0.05) associated with unstable angina at the time of the first procedure as well as diabetes and the female gender. Diabetes, the female gender and unstable angina were highly predictive factors of major adverse cardiac events during follow-up. CONCLUSIONS: Multiple vessel stenting in patients with multivessel coronary artery disease is associated with an acceptable immediate and long-term clinical outcome and could be considered as an alternative therapeutic option in these patients. Predictors of an adverse long-term outcome are the female gender and the presence of diabetes mellitus.

Immediate and long-term results of "T" stenting for bifurcation coronary lesions.

The technique of "T" stenting, which incorporates wiring both the branches of a bifurcation lesion, dilating a balloon in the main branch during stent deployment in the side branch followed by deployment of stent in the main branch, provides excellent immediate results in terms of technical and procedural success. However, further innovations are mandated to optimize the long-term outcome, which with a restenosis rate of 63%, can be described as not encouraging.

Direct coronary stenting without predilation.

OBJECTIVES: Coronary stenting is the primary therapeutic option for percutaneous treatment of many coronary lesions, after the risk of subacute stent thrombosis and bleeding complications has been reduced by improved antithrombotic regimens and high pressure stent expansion. BACKGROUND: Direct stent implantation (without predilation) has been considered a promising new technique that may reduce the procedure time, radiation exposure time and cost. METHODS: After having reviewed all cases of stent implantation from February to June 1998 (n = 585), 185 (32%) of these patients were retrospectively considered candidates for direct stent implantation without predilation, according to prespecified criteria (i.e., absence of severe coronary calcifications and/or tortuosity of the lesion or the segment proximal to the lesion). By operator preference, direct coronary stent implantation was actually attempted in 123 (21%) of the 585 patients (100 men, 60 +/- 10 years old) on 123 lesions. The impact of direct stenting in terms of cost, procedure time, radiation exposure time and amount of contrast dye used was assessed by comparing the two groups of patients who underwent single-vessel stenting without (n = 69) and with (n = 46) predilation. RESULTS: Direct stenting was successful in 118 patients (96%). No acute or subacute complications occurred in these patients. Procedure time, radiation exposure time and cost were significantly lower in the group of patients who had single-vessel direct versus conventional stenting (45 +/- 31 vs. 64 +/- 46 min, 12 +/- 9 vs. 16 +/- 10 min and 1,305 +/- 363 vs. 2,210 +/- 803 Euro, respectively; p < 0.05 for all). CONCLUSIONS: Direct stenting without predilation in selected lesions seems to be a safe and successful procedure that provides a way to contain cost and to shorten radiation exposure time.

[Evaluation of efficacy and mechanism of action of angioplasty and directed atherectomy assisted by intravascular ultrasonography]. / Ocena skutecznosci i mechanizmów dzialania angioplastyki oraz aterektomii kierunkowej za pomoca ultrasonografii wewnatrznaczyniowej.

Intravascular ultrasound (IVUS) is a unique method of coronary lumen visualization enabling also examination the structure of the artery wall. Aim of this study was to assess efficacy and mechanisms of action of balloon angioplasty (PTCA) and directional atherectomy by means of IVUS. IVUS examination was performed before and after mechanical revascularization procedure in 37 pts (DCA-19 pts, PTCA-18 pts). Both PTCA and DCA resulted in enlargement of the coronary artery lumen (2.29 +/- 1.19 mm2 vs 2.93 +/- 1.55 mm2) but, also external diameter of the vessel increased after the procedure (1.94 +/- 1.10 mm2 and 0.74 +/- 1.01 mm2 retrospectively). In 55.6% of cases after PTCA plaque rupture or artery wall dissection was observed, mainly in eccentric lesions (70%). IVUS allowed to recognize details of artery lumen and define efficiency of procedure. In about 15% cases decision to continue PTCA or DCA was made on the basis of IVUS images only. The mechanism in which PTCA modifies the artery lumen is diverse and depends on the structure of lesion. Factors possibly responsible for enlargement of the lumen are: stretching, squeezing and translocation of atheroma as well as cracking and dissections along the arterial wall. DCA effectiveness depends on the withdraw of the atheromatous deposit, however, in over one-half of cases also stretching has some effect.

Correlation between clinical and morphologic findings in unstable angina.

This study was undertaken to verify the hypothesis that the discrepant findings in published reports on the prevalence of thrombus in unstable angina depend on the inclusion of different clinical subsets in the various studies. We therefore correlated the clinical characteristics of patients included under the label of unstable angina with the morphologic features assessed by coronary angiography and intravascular ultrasound, and with histopathologic findings of atherectomy specimens. Fifty-eight patients with unstable angina (class B of the Braunwald classification) undergoing coronary arteriography followed by either coronary angioplasty (n = 20) or directional coronary atherectomy (n = 38) were studied. Fifteen patients were in class IB and 43 were in class II to IIIB. Among these 43 patients with angina at rest, 28 had ST-segment elevation during pain, and 15 had ST-segment depression, and 26 developed negative T waves on the baseline electrocardiogram (ECG) as a result of prolonged or repeated episodes of resting chest pain. Intravascular ultrasound examination of the culprit lesion was performed in 43 patients before the interventional procedure, and histopathologic analysis of atherectomy specimens was performed in 38 patients. Complex lesion morphology by angiography was observed in 31 patients (53%) without any significant relation to various clinical subsets. Patients in Braunwald class IB had more calcific plaques than patients in class II to IIIB (p < 0.001). Among patients with angina at rest, those with negative T waves on the baseline ECG, as well as those with transient ST elevation during pain, had a significantly higher incidence of noncalcific lesions (p = 0.001 for both). Analysis of atherectomy specimens revealed acute coronary lesions (thrombus and/or intraplaque hemorrhage) in 18 patients (47%). The incidence of acute coronary lesions was significantly higher in patients with than without negative T waves on the baseline ECG (p = 0.005), and increased further when negative T waves were combined with ST elevation during pain (p = 0.001). Multivariate analysis revealed that the presence orf negative T waves on the baseline ECG was the only explanatory variable related to the presence of acute coronary lesions by histology (p = 0.03). Patient subsets included in the broad spectrum of unstable angina have different morphologic features and incidence of acute coronary lesions by histology. These data provide an explanation for the discrepant findings in published reports on the relevance of thrombus formation in the pathogenesis of unstable angina.

Influence of plaque composition on luminal gain after balloon angioplasty, directional atherectomy, and coronary stenting.

This study was conducted to correlate the acute luminal enlargement achieved by three different nonsurgical revascularization procedures in 79 patients (32 treated by balloon angioplasty, 29 by directional atherectomy, and 18 by coronary stenting) with the morphologic characteristics of coronary plaques assessed by preprocedure intravascular ultrasound. The absolute luminal gain was 2.41 +/- 1.54 mm2 for balloon angioplasty, 3.17 +/- 1.8 mm2 for directional atherectomy, and 4.56 +/- 1.45 mm2 for coronary stenting (p = 0.00005). However, when luminal gain was corrected for the external vessel area (luminal gain index), such difference was no longer present (0.22 +/- 0.12 for balloon angioplasty, 0.24 +/- 0.15 for directional atherectomy, and 0.30 +/- 0.12 for coronary stenting, p = not significant). Concentric plaques treated by coronary stenting had a higher luminal gain index than eccentric plaques (p = 0.01). A comparison of the three devices showed that a similar luminal gain index was achieved in soft plaques, whereas coronary stenting was superior to directional atherectomy (0.41 +/- 0.10 vs 0.20 +/- 0.09, p = 0.002) and balloon angioplasty (0.41 +/- 0.10 vs 0.19 +/- 0.08, p = 0.0005) in concentric plaques. Coronary stenting also induced a greater luminal gain index than directional atherectomy in calcific plaques (0.30 +/- 0.11 vs 0.18 +/- 0.09, p = 0.04). In conclusion, these data show that plaque morphology assessed by preprocedure intracoronary ultrasound influences the acute luminal enlargement achieved by different coronary interventions. The knowledge of plaque composition may be useful in guiding the choice of the device to be used to obtain a larger acute luminal gain.

Influence of plaque morphology on the mechanism of luminal enlargement after directional coronary atherectomy and balloon angioplasty.

OBJECTIVE: To relate the mechanism of luminal gain after directional atherectomy and balloon angioplasty to the morphological characteristics of the coronary lesions, assessed by intravascular ultrasound imaging. DESIGN: Intravascular ultrasound imaging was performed before and after the revascularisation procedure to assess the contribution of wall stretching and plaque reduction in luminal gain. SUBJECTS: 32 patients undergoing balloon angioplasty and 29 undergoing directional coronary atherectomy. MAIN RESULTS: The main luminal area in vessels treated by balloon angioplasty increased from 1.51 (SD 0.30) to 3.91 (1.09) mm2 (P < 0.0001) with a concomitant increase in total vessel area from 11.44 (2.73) to 13.07 (2.83) mm2 (P < 0.0001). Therefore stretching of the vessel wall accounted for 68% of the luminal gain while plaque reduction accounted for the remaining 32%. This mechanism ranged from 45% in non-calcific plaques to 81% in echogenic plaques. The main luminal area in vessels treated by directional atherectomy increased from 1.49 (0.32) to 4.68 (1.73) mm2 (P < 0.0001), with a concomitant increase of total vessel area from 13.61 (4.67) to 15.2 (4.04) mm2 (P = 0.006). Thus stretching of the vessel wall accounted for 49% of the luminal area gain and plaque reduction for the remaining 51%. The presence of calcium influenced the relative contribution of these two mechanisms to the final luminal gain after directional atherectomy, since in calcific plaques stretching of the vessel wall accounted for only 9% of the luminal gain as compared to 56% in non-calcific plaques. After balloon angioplasty there was greater evidence of coronary dissections (32% v 3% after directional atherectomy, P < 0.01) and plaque fissure (60% v 0%, P < 0.01). Plaque fissure was more frequently seen in echolucent and concentric lesions, whereas dissections prevailed in echogenic and eccentric lesions. CONCLUSIONS: Intravascular ultrasound imaging may allow the assessment of acute changes in lumen and vessel wall after revascularisation procedures, and help in evaluating the potential effect of the structure and morphology of coronary lesions on the mechanism of luminal enlargement.

[Assessment of the results during and after coronary recanalization procedures]. / Valutazione dei risultati durante e dopo procedura di ricanalizzazione coronarica.

PTCA and new-device angioplasty have dramatically altered the management of patients with symptomatic coronary artery disease. Concurrent with the technical improvement in coronary angioplasty, the methods used to evaluate procedural outcome during and after revascularization have also become more sophisticated. Quantitative coronary angiography, angioscopy, and intravascular ultrasound are the most important methods for decision making, monitoring the procedure and document the final results. However despite their overall research value, these qualitative and quantitative techniques may be of limited value to the clinical interventional cardiologist and are often complementary or redundant. If a choice of these techniques is necessary, on-line quantitative coronary angiography, and intravascular ultrasound are certainly the most helpful methods in a Cath Lab to evaluate procedural outcome.

Effects of coronary angioplasty on left ventricular function.

It is well known that myocardial revascularization after successful coronary bypass surgery results in improved left ventricular function. Coronary angioplasty also results in successful revascularization, favorably affecting both stunned and hibernating myocardium. We studied 22 patients with chronic stable angina who underwent successful angioplasty for an isolated narrowing of the proximal or midportion of the left anterior descending artery. These patients also performed isometric exercises before and after angioplasty, which can be used to characterize left ventricular function. Revascularization after angioplasty induced an immediate improvement in left ventricular function in those patients with dysfunction secondary to hibernating myocardium. Further studies are needed to assess the possibility of the myocardial stunning phenomenon occurring after angioplasty in those patients without left ventricular improvement.

[Coronary angioplasty in unstable angina]. / L'angioplastica coronarica nell'angina instabile.

Percutaneous transluminal coronary angioplasty is now largely applied either to stable or unstable patients suffering from angina pectoris. The procedural success rate and the incidence of acute complications are now comparable in the 2 population of patients. Very recent data have also shown that there is no difference in restenosis between patients with stable or unstable angina. Therefore, by now, in such unstable coronary syndromes the choice of surgical therapy is mainly determined by the presence of multivessel disease or by depressed left ventricular function. However, the possibility to obtain a complete revascularization by angioplasty or to stabilize the patients treating only the "culprit" vessel, may increase the number of unstable patients shifting from surgery to angioplasty.