Colchicine in Cardiovascular Disease: In-Depth Review.

Inflammation plays a prominent role in the development of atherosclerosis and other cardiovascular diseases, and anti-inflammatory agents may improve cardiovascular outcomes. For years, colchicine has been used as a safe and well-tolerated agent in diseases such as gout and familial Mediterranean fever. The widely available therapeutic has several anti-inflammatory effects, however, that have proven effective in a broad spectrum of cardiovascular diseases as well. It is considered standard-of-care therapy for pericarditis, and several clinical trials have evaluated its role in postoperative and postablation atrial fibrillation, postpericardiotomy syndrome, coronary artery disease, percutaneous coronary interventions, and cerebrovascular disease. We aim to summarize colchicine's pharmacodynamics and the mechanism behind its anti-inflammatory effect, outline thus far accumulated evidence on treatment with colchicine in cardiovascular disease, and present ongoing randomized clinical trials. We also emphasize real-world clinical implications that should be considered on the basis of the merits and limitations of completed trials. Altogether, colchicine's simplicity, low cost, and effectiveness may provide an important addition to other standard cardiovascular therapies. Ongoing studies will address complementary questions pertaining to the use of low-dose colchicine for the treatment of cardiovascular disease.

Early arrhythmia recurrence after cryoballoon ablation in atrial fibrillation: A systematic review and meta-analysis.

INTRODUCTION: Early arrhythmia recurrence within the 3-month blanking period is a common event that historically has been attributed to reversible phenomena. While its mechanistic links remain obscure, accumulating evidence support the argument of shortening the blanking period. We aimed to elucidate the association between early and late arrhythmia recurrence after atrial fibrillation cryoablation. METHODS: The MEDLINE database, ClinicalTrials. gov, medRxiv, and Cochrane Library were searched for studies evaluating early and late arrhythmia recurrence rates in patients undergoing cryoablation for atrial fibrillation. Data were pooled by meta-analysis using a random-effects model. The primary endpoint was late arrhythmia recurrence. RESULTS: Early arrhythmia recurrence was found predictive of decreased arrhythmia-free survival after evaluating 3975 patients with paroxysmal or persistent atrial fibrillation who underwent cryoablation (odds ratio [OR]: 5.31; 95% confidence interval [CI]: 3.75-7.51). This pattern remained unchanged after subanalyzing atrial fibrillation type (paroxysmal; OR: 7.16; 95% CI: 4.40-11.65 and persistent; OR: 7.63; 95% CI: 3.62-16.07) as well as cryoablation catheter generation (first generation; OR: 5.15, 95% CI: 2.39-11.11 and advanced generation; OR: 5.83, 95% CI: 3.68-9.23). Studies permitting antiarrhythmic drug utilization during the blanking period or examining early recurrence as a secondary outcome were found to be a significant source of statistical heterogeneity. CONCLUSION: Our findings suggest that early arrhythmia recurrence is predictive of late outcomes after cryoablation for atrial fibrillation. Identifying which patients deserve earlier reintervention is an open research avenue.

Different venous approaches for implantation of cardiac electronic devices. A network meta-analysis.

OBJECTIVES: Many of the complications arising from cardiac device implantation are associated to the venous access used for lead placement. Previous analyses reported that cephalic vein cutdown (CVC) is safer but less effective than subclavian vein puncture (SVP). However, comparisons between these techniques and axillary vein puncture (AVP) - guided either by ultrasound or fluoroscopy - are lacking. Thus, we aimed to compare safety and efficacy of these approaches. METHODS: We searched for articles assessing at least two different approaches regarding the incidence of pneumothorax and/or lead failure (LF). When available, bleeding and infectious complications as well as procedural success were analyzed. A frequentist random effects network meta-analysis model was adopted. RESULTS: Thirty-six studies were analyzed. Most articles assessed SVP versus CVC. Compared to SVP, both CVC and AVP were associated with reduced odds of pneumothorax (OR: 0.193, 95%CI: 0.136-0.275 and OR: 0.128, 95%CI: 0.050-0.329; respectively) and LF (OR: 0.63, 95%CI: 0.406-0.976 and OR: 0.425, 95%CI: 0.286-0.632; respectively). No significant differences between AVP and CVC were demonstrated. Limited data suggests no major impact of different approaches on infectious and bleeding complications. Initial CVC approach required significantly more often an alternate/additional venous access for lead placement, compared to both AVP and SVP. No differences between these two were identified. CONCLUSION: Both AVP and CVC seem to decrease incident pneumothorax and LF, compared to SVP. Initial AVP approach seems to decrease the need of alternate venous access, compared to CVC. These results suggest that AVP should be further clinically tested.

Effect of cryoballoon and radiofrequency ablation for pulmonary vein isolation on left atrial function in patients with nonvalvular paroxysmal atrial fibrillation: A prospective randomized study (Cryo-LAEF study).

BACKGROUND: Isolation of the pulmonary veins (PVI) has become a mainstay in atrial fibrillation (AFib) therapy. Lesions in left atrial tissue lead to scar formation and this may affect left atrial function. METHODS: Patients with paroxysmal AFib were randomly assigned in a 1:2 allocation scheme to radiofrequency (RF) ablation or cryoballoon. Real-time three-dimensional echocardiography was performed (under sinus rhythm in all cases) before ablation and at 1 and 3 months to evaluate the left atrial functional indices. The primary outcome measure was change in left atrial ejection fraction (LAEF) at 1 month. RESULTS: 120 patients were randomized (80 to cryoballoon, 40 to RF). The absolute change in LAEF at 1 month was 4.0 (Q1-Q3, -0.1to 7.6)% in the cryoballoon group and -0.8 (Q1-Q3, -1.9 to 0.9)% in the RF group (P < 0.001 for the comparison between groups). At 3 months, the corresponding changes were 6.7 (Q1-Q3, 3.4-11.2)% and 0.7 (Q1-Q3, -0.7 to 3.5)%, respectively (P < 0.001). Overall, the rate of patients with lower LAEF at 3 months compared to baseline was 2.5% in the cryoballoon group and 32.5% in the RF group (P < 0.001). AFib recurrence rate at 6 months was higher in patients with decreased LAEF (odds ratio, 6.2; 95% confidence interval, 2.0-19.5; P = 0.002). CONCLUSION: The Cryo-LAEF study prospectively compared the effects of RF and cryoballoon ablation on left atrial function. Both at 1 and 3 months postablation, LAEF was either improved or stable in both ablation groups.

B-type natriuretic peptide levels and benign adiposity in obese heart failure patients.

Obesity is a major risk factor for the development of chronic heart failure (CHF) and does not only pose diagnostic challenges, but also has prognostic implications for these patients. Paradoxically, obese patients with CHF have a better prognosis than thinner individuals. In recent years, it has been demonstrated that the adipose tissue, even in patients with HF, is not always detrimental, and that obesity may coexist with a phenotype of benign adiposity without systemic metabolic abnormalities. Experimental data have shown that natriuretic peptides (NPs), and in particular brain natriuretic peptide (BNP), play a major role in the communication of the heart with the adipose tissue. Body fat distribution and adipose tissue function show a large degree of heterogeneity among depots and may explain the complex relationship between NPs and body fat. NPs can affect both the quality and the behaviour of fatty tissue, promoting a healthy adipocyte phenotype, and can favourably affect body fat metabolism. In this article, we review the existing literature on the bidirectional effects of BNP and adipose tissue in HF and highlight the complexity of this relationship.

Effect of Postablation Statin Treatment on Arrhythmia Recurrence in Patients With Paroxysmal Atrial Fibrillation.

BACKGROUND: Statins have been proposed as a means to prevent postablation atrial fibrillation (AF) recurrences, mainly on the basis of their pleiotropic effects. The objective of this subanalysis of a prospectively randomized controlled study population of patients undergoing radiofrequency ablation for paroxysmal AF was to test the hypothesis that statin treatment is associated with longer time to recurrence. METHODS AND RESULTS: This is a subanalysis over an extended follow-up period of a prospective randomized study (ClinicalTrials.gov Identifier NCT01791699). Among 291 patients, 2 propensity score-matched subgroups of patients who received or did not receive statins after pulmonary vein isolation were created. In the unmatched cohort, there was no difference in the rate of recurrence between statin-treated and not treated patients, with a 1-year recurrence estimate of 19% and 23%, respectively (Gehan statistic 0.59, P = 0.443). In the propensity-matched cohort (N = 166, 83 per group), recurrence-free survival did not differ significantly between groups (839 days, 95% confidence interval 755-922 days, in the no statin group vs. 904 days, 95% confidence interval 826-983 in the statin group; P = 0.301). The 1-year recurrence rate estimate was 30% in the no statin group versus 27% in the statin group (Gehan statistic 0.56, P = 0.455). CONCLUSION: Statin treatment does not seem to affect AF recurrence in following radiofrequency ablation for paroxysmal AF, over a follow-up time of about 2.5 years.

Effect of pulmonary vein isolation on left atrial appendage flow in paroxysmal atrial fibrillation.

BACKGROUND: Left atrial appendage (LAA) functional modification in the context of pulmonary vein isolation has been a focus point of research and LAA emptying flow velocity (LAAEFV) is considered to reflect LAA contractility, stunning, and fibrosis. OBJECTIVE: In the present study, we sought to prospectively evaluate short-term LAAEFV changes after radiofrequency (RF) or cryoballoon ablation in paroxysmal AF. METHODS: This was a prospective substudy of the Effect of Cryoballoon and RF Ablation on Left Atrial Function (CryoLAEF) study (ClinicalTrials.gov Identifier: NCT02611869). Thirty patients, randomly assigned to RF or cryoablation, were prospectively followed. Transesophageal echocardiograms were performed at baseline and at 3 months postablation to measure LAAEFV. RESULTS: All measurements were performed in sinus rhythm. Overall, LAAEFV was 44.2 [38.5-62.8] cm/s at baseline and was increased to 70.8 [64.8-77.6] cm/s at 3 months' postablation (P < 0.001). Baseline LAAEFV was 52.5 [37.7-68.0] cm/s in the RF group and 42.8 [38.7-52.9] cm/s in the CryoBalloon group (P  =  0.653). At 3 months, the corresponding values were 68.5 [61.9-76.6] cm/s and 73.9 [69.2-79.9] cm/s, respectively (P  =  0.081 for the difference between the two groups at 3 months). The median change in LAAEFV was 11.0 [4.7-26.2] cm/s in the RF group versus 29.6 [15.8-37.0] cm/s in the CryoBalloon group (P  =  0.033). CONCLUSION: LAA function is improved after catheter ablation with RF or balloon cryoablation in patients with paroxysmal AF, evaluated while in sinus rhythm both at baseline and on follow-up.

Coincidental ganglionated plexus modification during radiofrequency pulmonary vein isolation and post-ablation arrhythmia recurrence.

AIMS: Vagal responses (VR) during left atrial ablation for atrial fibrillation (AF) treatment have been reported to be associated with less recurrences, presumably because they are a sign of ganglionated plexi modification. Our objective was to evaluate whether coincidentally elicited VR during left atrial ablation are associated with lower AF recurrence rates. METHODS AND RESULTS: This is a post hoc analysis of a prospective study of 291 patients with paroxysmal AF undergoing radiofrequency pulmonary vein isolation (PVI). Vagal responses were defined as episodes of heart rate <40 bpm or asystole lasting >5 s elicited during energy application. Sixty-eight patients (23.4%) had a VR during ablation. In Kaplan-Meier analysis, mean recurrence-free survival was 449 days (95% confidence interval 411-488) in patients with VR when compared with 435 days (95% confidence interval 415-455) in those without (P = 0.310). The 12-month recurrence rate estimates were 25 and 27%, respectively. In an unadjusted Cox model, VR was associated with an odds ratio for recurrence of 0.77 (95% confidence interval 0.46-1.28). CONCLUSION: Coincidentally elicited VR during radiofrequency PVI in patients with paroxysmal AF do not appear to be related to lower risk of arrhythmia recurrence. This may mean that, even if a VR is truly a sign of coincidental ablation of a ganglionated plexus, this does not necessarily mean that a therapeutic modification has been effected, at least to a degree associated with clinical benefit.

Circulating Erythrocyte Microparticles and the Biochemical Extent of Myocardial Injury in ST Elevation Myocardial Infarction.

OBJECTIVES: Red blood cell microparticles (RBCm) have potential adverse vascular effects and they have been shown to be elevated in ST elevation myocardial infarction (STEMI). The purpose of this study is to investigate their relationship with biochemical infarct size. METHODS: RBCm were quantified with flow cytometry in blood drawn from 60 STEMI patients after a primary angioplasty. The creatine kinase-myocardial brain fraction (CK-MB) was measured at predefined time points and the area under the curve (AUC) was calculated. RESULTS: RBCm count was correlated with CK-MB AUC (Spearman's ρ = 0.83, p < 0.001). The CK-MB AUC values per RBCm quartile (lower to upper) were: 3,351 (2,452-3,608), 5,005 (4,450-5,424), 5,903 (4,862-10,594), and 8,406 (6,848-12,782) ng × h/ml, respectively. From lower to upper quartiles, the maximal troponin I values were: 42.2 (23.3-49.3), 49.6 (28.8-54.1), 59.2 (41.4-77.3), and 69.1 (48.0-77.5) ng/ml (p = 0.005). In multivariable analysis, RBCm remained a significant predictor of CK-MB AUC (standardized ß = 0.63, adjusted p = 0.001). CONCLUSIONS: Erythrocyte microparticles appear to be related to the total myocardial damage biomarker output. The exact pathophysiologic routes, if any, for this interaction remain to be identified. However, these results suggest that erythrocytes may be a - thus far virtually ignored - player in the pathogenesis of ischemic injury.

Assessment of the vulnerable carotid atherosclerotic plaque using contrast-enhanced ultrasonography.

Carotid atherosclerosis represents a primary cause for cerebrovascular ischemic events and its contemporary management includes surgical revascularization for moderate to severe symptomatic stenoses. However, the role of invasive therapy seems to be questioned lately for asymptomatic cases. Numerous reports have suggested that the presence of neovessels within the atherosclerotic plaque remains a significant vulnerability factor and over the last decade imaging modalities have been used to identify intraplaque neovascularization in an attempt to risk-stratify patients and offer management guidance. Contrast-enhanced ultrasonography of the carotid artery is a relatively novel diagnostic tool that exploits resonated ultrasound waves from circulating microbubbles. This property permits vascular visualization by producing superior angiography-like images, and allows the identification of vasa vasorum and intraplaque microvessels. Moreover, plaque neovascularization has been associated with plaque vulnerability and ischemic symptoms lately as well. At the same time, attempts have been made to quantify contrast-enhanced ultrasonography signal using sophisticated software packages and algorithms, and to correlate it with intraplaque microvascular density. The aim of this review was to collect all recent data on the characteristics, performance, and prognostic role of contrast-enhanced ultrasonography regarding carotid stenosis management, and to produce useful conclusions for clinical practice.

Antithrombotic therapy in patients undergoing TAVI with concurrent atrial fibrillation. One center experience.

Aim of the present study was to record the antithrombotic approach in AF and non-AF patients undergoing TAVI, and to compare the efficiency of the used regimens combination. Antithrombotic approach of patients undergoing TAVI remains a challenging dispute. It becomes even more complex when need for anticoagulant treatment is required due to concurrent atrial fibrillation. Consecutive patients with severe symptomatic aortic stenosis treated with TAVI, were retrospectively studied. All patients were divided into two groups, matched to age, depending on the existence of atrial fibrillation. The primary end-point was the composite of MACE, while the secondary end-point was the occurrence of major bleeding at follow-up. A total of 80 patients were included in the study. Out of them, 20 patients (80.2 ± 5.4 years) suffered from concurrent atrial fibrillation. This group was matched with 20 patients (80.6 ± 3.7 years) with no need for anticoagulation. AF-group patients were treated with clopidogrel plus acenocoumarol for 3 months. Following that, acetylsalicylic acid plus acenocoumarol were prescribed. Non-AF patients were treated with 3 months clopidogrel plus acetylsalicylic acid followed by single acetylsalicylic acid medication. No statistical significant differences in MACE between AF and non-AF group were identified (p = 0.705, phi coefficient = 0.06) (mean follow-up 23.4 ± 14 months). Similarly, there was no statistical significant difference for bleedings among the AF and non-AF patient group (p = 0.658, phi coefficient = 0.14). In patients undergoing TAVI with CoreValve, with concurrent AF, treatment with clopidogrel plus acenocoumarol for 3 months, followed by acetylsalicylic acid plus acenocoumarol, seems safe and effective enough in long-term follow-up.

Inferior epigastric artery as a landmark for transfemoral TAVI. Optimizing vascular access?

OBJECTIVES: This study sought to investigate whether the site of common femoral artery (CFA) cannulation in regard to the inferior epigastric artery (IEA) is associated with the incidence of vascular complications in patients undergoing transfemoral aortic valve implantation (TAVI). BACKGROUND: Vascular access complications are a main issue during TAVI and have been associated with significant increase of morbidity and mortality. The need for establishment of reliable predictors for these serious events remains important. METHODS: A total of 90 patients, who had undergone TAVI, were retrospectively studied. Vascular complications were defined as major and minor according to the Valve Academic Research Consortium (VARC) criteria. Patients were divided into high cannulation site (CS) group and low CS group depending on the common femoral artery puncture site position, in regards to the most inferior border of the IEA. RESULTS: Vascular complications were significantly more frequent in the high CS group versus the low CS group (32.3% vs. 11.9%, P = 0.039). High cannulation remained an independent predictor of vascular complications after adjustment for known risk factors (OR: 4.827, CI: 1.441-16.168; P = 0.011). CONCLUSIONS: In patients undergoing transfemoral TAVI, arterial puncture above the most inferior border of the IEA is associated with vascular complications.

Assessment of left atrial function after percutaneous closure of patent foramen ovale.

BACKGROUND: The influence of atrial septal occluders in left atrial (LA) function after percutaneous closure of patent foramen ovale (PFO) has not been thoroughly studied. METHODS: Twenty-five patients (mean age 40.7 ± 12 years) undergoing percutaneous PFO closure were enrolled in this study. Transthoracic echocardiogram (TTE) was performed 3 and 6 months before the procedure. Volumetric indices (active emptying fraction: LA AEF, expansion index: LA EI, and passive emptying fraction: LA PEF), strain and strain rate (SR), were calculated during the contractile, reservoir, and conduit LA phases for the lateral, anterior, and inferior LA walls with TTE. RESULTS: After 3 months, a decrease in the SR of the LA anterior wall was observed (from 2.12 ± 0.22 to 1.66 ± 0.26, P < 0.045), while the LA lateral wall strain was found to be increased (from 0.708 ± 0.15 to 0.783 ± 0.159, P < 0.001). Moreover, simultaneously LA AEF was greater compared with baseline (from 31.0 ± 1.6 to 34.0 ± 1.6, P < 0.004). However, all these alterations reversed at 6 months. CONCLUSIONS: Segmental LA function is altered transiently after percutaneous PFO closure with a septal occlude. The LA anterior wall SR decreases, while the lateral wall strain increases. The impact of these alterations needs further clarification.

Quantitative analysis of carotid plaque vasa vasorum by CEUS and correlation with histology after endarterectomy.

BACKGROUND: Intraplaque neovascularization and vasa vasorum (VV) proliferation contribute in the progression and rupture of atherosclerotic lesions. Contrast enhanced ultrasonography (CEUS) has been reported to attain data regarding intraplaque neovessels and VV. However, whether the detection of microbubbles by CEUS within atherosclerotic plaques truly represents microvessels is a point of concern. We aimed to evaluate stable and unstable carotid artery plaque (CAP) VV pattern by CEUS and its correlation with histology and immunochemistry. PATIENTS AND METHODS: Patients with CAP scheduled for plaque endarterectomy were enrolled. CAP was initially identified by conventional ultrasonography and subsequently CEUS (harmonic ultrasound imaging with simultaneous intravenous contrast agent injection) was performed. The recorded image loops were evaluated by a semi-automated method. Plaque specimens were excised and underwent histological and immunochemical (for CD34, Vascular Endothelial Growth Factor, CD68 and CD3 antibodies) analysis. RESULTS: Fourteen patients (67.6 ± 10.2 years, 10 males) with a 86.9 ± 11.5 % degree of carotid artery stenosis were evaluated. Histology showed that half of the plaques were unstable. Enhancement of plaque brightness on CEUS was significant for both stable and unstable plaque subgroups (p = 0.018 for both). Immunochemistry showed that microvessels, as assessed by CD34 antibody, were more dense in unstable vs. stable plaques (36.6 ± 17.4 vs. 13.0 ± 7.2 respectively, p = 0.002). However, correlation between plaque brigthness enhancement on CEUS and microvessel density was significant only for stable (r = 0.800, p = 0.031) plaques. CONCLUSIONS: The identification of brightness enhacement during CEUS in carotid atherosclerotic plaques may not always reflect the presence of VV.