Charalampos Kossyvakis

Cardioprotective Role of Remote Ischemic Periconditioning in Primary Percutaneous Coronary Intervention: Enhancement by Opioid Action

OBJECTIVES We sought to determine the potential of remote ischemic periconditioning (RIPC), and its combination with morphine, to reduce reperfusion injury in primary percutaneous coronary interventions. BACKGROUND Remote ischemic post-conditioning is implemented by applying cycles of ischemia and reperfusion on a remote organ, which result in release of circulating factors inducing the effects of post-conditioning on the myocardium. METHODS A total of 96 patients (59 men) were enrolled. The patients were randomized to groups as follows: 33 to each treatment group (Group A: RIPC; Group B: RIPC and morphine) and 30 to the control group (Group C). Measures of efficacy were achievement of full ST-segment resolution (primary), and reduction of ST-segment deviation score and peak troponin I during hospitalization. RESULTS A higher proportion of patients in Groups A (73%) and B (82%) achieved full ST-segment resolution after percutaneous coronary intervention, compared with control patients (53%) (p = 0.045). Peak troponin I was lowest in Group B, 103.3 +/- 13.3 ng/ml, in comparison to peak levels in Group A, 166.0 +/- 28.0 ng/ml, and the control group, 255.5 +/- 35.5 ng/ml (p = 0.0006). ST-segment deviation resolution was 87.3 +/- 2.7% in Group B, compared with 69.9 +/- 5.1% in Group A and 53.2 +/- 6.4% in the control group (p = 0.00002). In paired comparisons between groups, Group B did better than the control group in terms of both ST-segment reduction (p = 0.0001) and peak troponin I (p = 0.004), whereas Group A differences from the control group did not achieve statistical significance (p = 0.054 and p = 0.062, respectively). CONCLUSIONS These findings demonstrate a cardioprotective effect of RIPC and morphine during primary percutaneous coronary intervention for the prevention of reperfusion injury. This is in agreement with observations that the beneficial effect of RIPC is inhibited by the opioid receptor blocker naloxone.

Colchicine for prevention of atrial fibrillation recurrence after pulmonary vein isolation: Mid-term efficacy and effect on quality of life

BACKGROUND Our group previously showed that colchicine treatment is associated with decreased early recurrence rate after ablation for atrial fibrillation (AF). OBJECTIVE The purpose of this study was to test the mid-term efficacy of colchicine in reducing AF recurrences after a single procedure of pulmonary vein isolation in patients with paroxysmal AF. Assessment of quality-of-life (QOL) changes was a secondary objective. METHODS Patients with paroxysmal AF who were scheduled for ablation were randomized to a 3-month course of colchicine 0.5 mg twice daily or placebo and were followed for a median of 15 months (with a 3-month blanking period). QOL was assessed with a general-purpose health-related QOL tool (26-item World Health Organization QOL questionnaire) at baseline and after 3 and 12 months. RESULTS Two hundred twenty-three randomized patients underwent ablation, and 206 patients were available for analysis (144 male, age 62.2 ± 5.8 years). AF recurrence rate in the colchicine group was 31.1% (32/103) vs 49.5% (51/103) in the control group (P = .010), translated in a relative risk reduction of 37% (odds ratio 0.46, 95% confidence interval 0.26-0.81). The number needed to treat was 6 (95% confidence interval 3.2-19.8). Physical domain QOL scores at 12 months were 63.6 ± 13.8 in the colchicine group and 52.5 ± 18.1 in controls, whereas psychological domain scores were 56.1 ± 13.7 vs 44.7 ± 17.3, respectively (P <.001, for both). CONCLUSION Colchicine treatment after pulmonary vein isolation for paroxysmal AF is associated with lower AF recurrence rates after a single procedure. This reduction is accompanied by corresponding improvements in physical and psychological health-related QOL scores.

Colchicine and the Heart: Pushing the Envelope

Colchicine, a natural and ancient drug still used today, is traditionally considered the staple therapy for gout and a second-line treatment for pericarditis, as well as a basic part of familial Mediterranean fever and Behcets disease management. It is commonly classified as an anti-inflammatory agent, although its mechanism of action does not involve the arachidonic acid pathway affected by non-steroid anti-inflammatory drugs and glucocorticoids. Colchicine inhibits microtubule polymerization by binding to tubulin, thus affecting any process that requires cytoskeletal changes, including cell mitosis and neutrophil motility. Recent studies suggest that colchicine may prove to be useful in a much wider spectrum of cardiovascular diseases than previously suspected, rekindling the interest in this old drug. In this review we briefly present the biochemical characteristics, mechanism of action and side-effects of colchicine, as well as examine what is currently known about the promising role of colchicine in cardiovascular medicine beyond pericardial disease.

NTproBNP: An Important Biomarker in Cardiac Diseases

Natriuretic neuropeptides (ANP, BNP, CNP) are produced primarily in the cardiac atria under normal conditions. The main stimulus for ANP and BNP peptide synthesis and secretion is cardiac wall stress. Cardiac ventricular myocytes constitute the major source of BNP-related peptides. Ventricular NT-proBNP production is upregulated in cardiac failure and locally in the area surrounding a myocardial infarct. NT-proBNP is cleared passively by organs with high rate of blood flow (muscle, liver, kidney). It has a longer half life than BNP and higher plasma concentration. BNP and NTproBNP tend to be higher in women and lower in obese individuals. They are also higher in elderly, in left ventricular tachycardia, right ventricular overload, myocardial ischemia, hypoxaemia, renal dysfunction, liver cirrhosis, sepsis and infection. NT-proBNP is useful both in the diagnosis and prognosis of heart failure and is considered to be a gold standard biomarker in heart failure similar to BNP. A cut-off point 300 pg/ml has 99% sensitivity, 60%specificity and NPV 98%for exclusion of acute heart failure. NT proBNP has also a strong prognostic value of death in acute and chronic heart failure and also predicts short and long term mortality in patient with suspected or confirmed unstable CVD. Natriuretic peptides are also prognostic markers for the RV (Right Ventricular) Dysfunction. Their release is due to myocardial stretch from right ventricular pressure overload.Finally, there are data supporting that NT-proBNP might be useful to put a time frame on atrial fibrillation of unknown onset.

CHADS2 and CHA2DS2-VASc scores as predictors of left atrial ablation outcomes for paroxysmal atrial fibrillation

AIMS The selection of patients with atrial fibrillation (AF) that will benefit most by left atrial ablation remains suboptimal. CHADS2 score has been shown to be associated with post-ablation AF recurrences. However, data regarding the CHA2DS2-VASc score are lacking. In addition, there is paucity of data regarding the exact predictive value, in terms of sensitivity and specificity, of each of these scores as to AF recurrence. This study aimed to evaluate the merit of the CHADS2 and CHA2DS2-VASc scores in predicting arrhythmia recurrence after a single ablation procedure for paroxysmal AF. METHODS AND RESULTS One hundred and twenty-six patients (78 males, median age 61 years) with symptomatic paroxysmal AF underwent left atrial ablation. Over 16 months (interquartile range: 10.8-26.0), 89 patients were recurrence-free (70.6%). Larger left atrial volume (P: 0.039), diabetes (P: 0.001), dyslipidemia (P: 0.003), coronary artery disease (P: 0.003), class III antiarrhythmic drugs (P: 0.017), CHADS2 (P: 0.006), and CHA2DS2-VASc (P: 0.016) scores were univariately associated with recurrence. In the multivariate analysis, both CHADS2 (hazard ratio: 1.91, 95% confidence interval 1.09-3.36, P: 0.023) and CHA2DS2-VASc (hazard ratio: 1.97, 95% confidence interval 1.16-3.33, P: 0.012) were independently associated with AF recurrence. Cut-off analysis showed that a score ≥2 for both the CHADS2 (sensitivity = 46% and specificity = 79%, area under the Receivers operating characteristic curve, AUC = 0.644) and CHA2DS2-VASc score (sensitivity = 57% and specificity = 65%, AUC = 0.627) showed the highest predictive value for AF recurrence. CONCLUSIONS CHA2DS2-VASc score is an independent predictor of left atrial ablation outcomes for paroxysmal AF, with a similar predictive value to CHADS2. However, the predictive accuracy of both is mediocre.

Estimation of atrial fibrillation recency of onset and safety of cardioversion using NTproBNP levels in patients with unknown time of onset

Objective As shown previously in patients with new-onset atrial fibrillation (AF) without symptoms or signs of heart failure, N-terminal pro-brain natriuretic peptide (NTproBNP) increases rapidly, reaching a maximum within 24–36 h, and then decreases even if AF persists. A study was undertaken to use NTproBNP measurements in patients with AF of unknown time of onset to identify patients with presumed recent onset of the arrhythmia. Design Two-group open cross-sectional study. Setting Hospitalised patients in cardiology departments of four hospitals. Patients Patients presenting with AF of unknown onset and no signs or symptoms of heart failure were separated into two groups: group A with NTproBNP above the cut-off level and group B with a low NTproBNP level. Interventions No therapeutic intervention. All patients underwent transoesophageal echocardiography (TEE). Main outcome measures Presence of left atrial thrombus on TEE. Results In group A (N=43) only two patients (4.7%) were found to have an atrial thrombus on TEE (negative predictive value of raised NTproBNP levels 95.3%) compared with 13 of 43 patients in group B (30.2%; p=0.002). Patients with a higher CHA2DS2VASc score (p=0.002) and a larger left atrium (p<0.001) were more likely to have an atrial thrombus. In the multivariate analysis, NTproBNP below the cut-off level was the most powerful predictor of the presence of thrombus (OR 25.0; p=0.016). Conclusion The reported strong correlation between raised NTproBNP levels and the absence of atrial thrombi on TEE suggests that the short-term increase in NTproBNP levels after AF onset might be used to assess the age of the arrhythmia and thus the safety of cardioversion in patients with AF of unknown onset and no heart failure.

Association of soluble tumour necrosis factor-related apoptosis-inducing ligand levels with coronary plaque burden and composition

Background Evidence shows that the soluble tumour necrosis factor-related apoptosis-inducing ligand (sTRAIL) may play a protective role against atherosclerosis. This study sought to investigate the potential association of sTRAIL levels with intravascular ultrasound (IVUS) and virtual histology characteristics of coronary plaques. Methods Patients with stable angina or positive for ischaemia non-invasive test were submitted to left cardiac catheterisation. Coronary blood samples were collected and sTRAIL was measured. Coronary arteries with at least one 50% or greater stenosis were studied with IVUS. Results 56 coronary arteries were studied with significant coronary artery disease. Plaque volume per unit of arterial length was 63±5 mm3/cm in arteries at the lower quartile of sTRAIL concentration versus 30±4 mm3/cm at the upper quartile (p<0.001; 95% CI of the difference 19.7 to 46.3 mm3/cm). The necrotic core and fibrofatty content of atheromatous plaques were inversely associated with sTRAIL (p<0.001). Thin-cap fibroatheromas (TCFA) were discovered in 16 of the 56 arterial segments. The mean sTRAIL concentration in these segments was 56.8±7.5 pg/ml versus 99.9±5.7 pg/ml in those without TCFA (p<0.001; 95% CI of the difference 22.7 to 63.5 pg/ml). The association of sTRAIL with the presence of TCFA remained significant in the logistic multivariate analysis (p=0.009). Conclusion According to the findings of the present study, in addition to coronary artery disease burden, the sTRAIL concentration is also related to the composition of atheromatous plaques. A significant association is demonstrated between low sTRAIL levels and the presence of TCFA, the IVUS–virtual histology prototype of the vulnerable plaque.

Radial artery flow-mediated dilation predicts arterial spasm during transradial coronary interventions.

Background: Transradial coronary catheterization has emerged over the last years as a favorable catheterization practice, based on evidence that it is associated with less vascular complications and shorter hospital stays. However, access site crossover appears to be more frequent when the initial route is the transradial one, one of the main reasons being arterial spasm. We hypothesized that radial flow‐mediated dilation (FMD) measurements could be used as a preprocedural method to assess the likelihood of arterial spasm. Methods: The study population consisted of patients scheduled for transradial diagnostic catheterization in whom ad hoc percutaneous coronary intervention (PCI) was performed. FMD was measured 1–2 days before PCI. The primary endpoint of the study was operator‐defined (operators were blinded as to the FMD results) radial artery spasm. Results: A total of 172 patients (110 male, age 65.3 ± 9) were included. Radial artery spasm was recorded in 13 patients (7.6%). FMD showed a very significant univariate association with the occurrence of spasm (P < 0.001) and was the most important predictor of spasm in the multivariate logistic regression analysis (beta −3.15; P < 0.001), followed by baseline radial artery diameter (P = 0.04), the number of catheters used (P = 0.049) and the administered volume of contrast medium (P = 0.017). Conclusion: Preprocedural FMD is a significant predictor of arterial spasm before elective transradial PCI. It is a low cost, safe, and feasible noninvasive modality, whose results might be taken into account when deciding on the vascular access route for an elective procedure, the size of sheaths or catheters to be used or the intensity of antispasm medication.© 2010 Wiley‐Liss, Inc.

Short-term fluctuations of plasma NT-proBNP levels in patients with new-onset atrial fibrillation: a way to assess time of onset?

Objective The objective of this study was to characterise short-term kinetics of plasma amino-terminal pro-B natriuretic peptide (NT-proBNP) levels in patients with new-onset atrial fibrillation (AF) without heart failure. Design Prospective cohort study. Setting Emergency departments and inpatient services of three large community hospitals. Patients 31 consecutive patients with new-onset atrial fibrillation (<24 h before presentation) persisting at least 48 h, without evidence of heart failure. Main outcome measures Plasma NT-proBNP levels were obtained at presentation and then 6, 12, 18, and 24 h after presentation. A final sample was obtained 48 h after onset of AF. Results Mean plasma NT-proBNP levels and 95% CIs (pg/ml) during the 48-h period following onset of AF were: 0–6 h: 636 (395 to 928), 6–12 h: 1364 (951 to 1778), 12–18 h: 1747 (1412 to 2083), 18–24 h: 1901 (1549 to 2253), 24–36 h: 1744 (1423 to 2066) and 36–48 h: 1101 (829 to 1373). Mean time to peak NT-proBNP levels was 16.7 (0.7) h; 29 patients reached their peak levels within 24 h. The mean peak NT-proBNP level was significantly higher than those obtained at 0–6 h and at 36–48 h after onset of AF (p<0.001 for both). There was no correlation between ventricular rate and plasma NT-proBNP levels during any time period after onset of AF. Conclusion In patients with new-onset AF but no clinical or radiographic evidence of heart failure, plasma NT-proBNP levels rise progressively to a peak during the first 24 h and then rapidly fall. This pattern may serve as an aid to assess the time from AF onset.

Interatrial conduction time and incident atrial fibrillation: a prospective cohort study.

BACKGROUND Atrial electrical conduction properties have been implicated in atrial fibrillation (AF) pathogenesis. OBJECTIVE The purpose of this study was to prospectively assess the potential association of interatrial conduction time (IACT) with incident AF. METHODS The study included persons referred for invasive electrophysiologic study (EPS), aged ≥50 years, without AF history or valvular disease. IACT was defined as the interval between the high right atrium electrogram and the distal coronary sinus atrial electrogram. RESULTS Six hundred twelve subjects were included (median follow-up 43 months, interquartile range 40-47). AF incidence was 21.7 cases per 1000 person-years. IACT was a significant predictor of AF with a c-statistic of 0.770 (95% confidence interval 0.702-0.838). In time-dependent analysis, IACT was a significant stratifier of AF risk (log-rank 28.0, P <.001). The corresponding incidences of AF in each tertile of IACT were 3, 17, and 46 per 1000 person-years, respectively (all differences between tertiles were significant). IACT remained significant in multivariable Cox regression analysis, after adjustment for age, sex, hypertension, and left atrial diameter, with each millisecond of prolonged IACT corresponding to 7% (95% confidence interval 2%-12%) higher adjusted risk of incident AF. CONCLUSION IACT is independently associated with incident AF. The invasive nature of the measurement is a limitation for its use as a clinical risk stratifier (although it could be used in patients referred for EPS), but these results are of interest in themselves because they suggest a strong pathophysiologic connection between atrial conduction times and substrate alterations ultimately leading to AF.