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.

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.

Efficacy of a new transdermal nitroglycerin patch (Deponit 10) for stable angina pectoris.

In this double-blind randomized placebo-controlled crossover study, the antianginal and anti-ischemic effect of a new transdermal system, releasing 10 mg of nitroglycerin (NTG) over 24 hours, was assessed in 19 outpatients with stable exercise-induced angina pectoris. The trial consisted of a 3-day washout: a 1-week period with verum or placebo patch followed by a second 1-week period with the other patch. During the study only sublingual NTG was allowed, and its consumption and the number of attacks recorded. Treadmill exercise tests were performed at the end of washout before patch application (baseline test) and 3 and 24 hours, respectively, after each period of 7 days of application of 1 patch daily. Systolic blood pressure and heart rate did not vary significantly at rest in the 17 patients who completed the trial. Angina was reduced 31.3% and NTG consumption 34.3% (p less than 0.01) during the week with Deponit 10 as compared with placebo. Exercise duration increased 29 and 16.1% (p less than 0.001 and p less than 0.1, respectively) at 3 and 24 hours with a verum patch as compared with placebo. ST-segment depression at comparable loads decreased 69 and 40.5% (p less than 0.01) at 3 and 24 hours, respectively, after application of Deponit. Onset of angina was delayed and maximal heart rate-blood pressure product significantly increased at 3 and 24 hours of treatment. It is concluded that Deponit 10 patch is effective in reducing anginal attacks and in increasing exercise capacity up to 24 hours after application.

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.

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.

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.

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.

[Electric alternans of QRS: its electrophysiologic significance in narrow QRS supraventricular paroxysmal tachycardia]. / Alternanza elettrica del QRS: suo significato elettrofisiologico nelle TPSV a QRS stretto.

The results of 22 patient's transesophageal electrophysiologic studies were analyzed to value the meaning of QRS alternans during narrow QRS tachycardia. Standard ECG showed ventricular pre-excitation in eight patients. QRS alternans were in six of them: heart rate was included between 230 and 374 m/sec (301.8 +/- 42 m/sec); in the remaining 16 patients, heart rate was included between 240 and 450 m/sec (350.0 +/- 42 m/sec). Our findings suggest that QRS alternans is related to the rate of tachycardia rather than to the presence of an accessory pathway.

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.

[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.

[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.

[The vectorcardiogram in A-V canal in the first three years of life: qualitative and quantitative analysis (author's transl)]. / Il vettocardiogramma del canale atrio-ventricolare (CAV) nei primi 3 anni di vita. Analisi qualitativa e quantitativa

The electrocardiograms and the vectocardiograms of 26 childrens, up to 3 years of age, affected by A-V canal, were been analyzed. The pattern of QRS loop in the 3 planes, the voltage of right maximum spatial vector (RMSV) and left maximum spatial vector (LMSV), their projection onto the horizontal (azimuth) and frontal plane (elevation) were related to right ventricular systolic pressure. The qualitative and quantitative evaluation of VCG Showed a better correlation with the haemodynamic data than the electrocardiogram. In all but 3 cases, the high frequency of superior orientation and counterclockwise rotation of QRS loop in the frontal plane was found; moreover the good correlation of right ventricular systolic pressure to the rotation of QRS loop on the horizontal plane was also confirmed. In fact, the latter was counterclockwise in the cases with a low pressure, whereas it became clockwise in those with higher pressure. Moreover a good direct correlation of the right ventricular pressure with forward orientation of LMSV on the horizontal plane was found. In differential diagnoses with other congenital heart diseases with superior orientation and anticlockwise rotation on the frontal plane, useful results were obtained by using the calculation of elevation time (the interval between point 0 and intersection of the QRS loop with the axis) which is significantly lower in the A-V canal. Terminal forces directed posteriorly and to the right and with a delay no longer than 0,03 inches do not warrant the diagnosis of left anterior hemiblock with a right bundle branch block associated. On the contrary, on the basis of anatomical and electrophysiologic studies we believe that in this disease there is an asinchrony in the activation i.e. the postero-inferior region, then the left lateral wall and finally the tree high part of right ventricle wall are sequentially activated.

A case of isolated atrioventricular discordance.

A case of isolated atrioventricular discordance in situs solitus is described. The importance of a well defined situs and of the presence of both ventricles in making this diagnosis is underlined and previous published reports reviewed. It is suggested that the haemodynamic concept of isolated atrioventricular discordance cannot be described only by the spatial relation between the ventricles (isolated ventricular inversion), but it should be indicted by the pattern of the connection between various flows, as shown by hearts with a normal relation between the ventricles and crossed atrioventricular connection.

[Acute treatment with verapamil of paroxysmal supraventricular tachycardia and atrial flutter in paediatric age (author's transl)]. / Trattamento acuto della tachicardia parossistica sopraventricolare e del flutter con verapamil, nell'etá pediatrica.

43 patients, 3 days to 12 years old, presented 68 paroxysms of supraventricular tachycardia and 2 crises of atrial flutter. 6 patients had a WPW syndrome and only 7 had an associated cardiac disease; the remaining had no other complaint but the arrhythmia. Verapamil, administered in the dose of 0.125-0.25 mg/Kg intravenously, interrupted critically the tachycardia in virtually all cases. The flutter was converted to atrial fibrillation with a slower ventricular rate. No adverse effects were observed but in two cases: one had a cardiac arrest promptly relieved and another a ventricular bradycardia corrected by atropine. Both cases had received an overdose of the drugs.