Intravascular Lithotripsy for the Treatment of Stent Underexpansion: The Multicenter IVL-DRAGON Registry.

Background: Whereas the efficacy and safety of intravascular lithotripsy (IVL) have been confirmed in de novo calcified coronary lesions, little is known about its utility in treating stent underexpansion. This study aimed to investigate the impact of IVL in treating stent underexpansion. Methods and Results: Consecutive patients with stent underexpansion treated with IVL entered the multicenter IVL-Dragon Registry. The procedural success (primary efficacy endpoint) was defined as a relative stent expansion >80%. Thirty days device-oriented composite endpoint (DOCE) (defined as a composite of cardiac death, target lesion revascularization, or target vessel myocardial infarction) was the secondary endpoint. A total of 62 patients were enrolled. The primary efficacy endpoint was achieved in 72.6% of patients. Both stent underexpansion 58.5% (47.5−69.7) vs. 11.4% (5.8−20.7), p < 0.001, and the stenotic area 82.6% (72.4−90.8) vs. 21.5% (11.1−37.2), p < 0.001, measured by quantitative coronary angiography improved significantly after IVL. Intravascular imaging confirmed increased stent expansion following IVL from 37.5% (16.0−66.0) to 86.0% (69.2−90.7), p < 0.001, by optical coherence tomography and from 57.0% (31.5−77.2) to 89.0% (85.0−92.0), p = 0.002, by intravascular ultrasound. Secondary endpoint occurred in one (1.6%) patient caused by cardiac death. There was no target lesion revascularization or target vessel myocardial infarction during the 30-day follow-up. Conclusions: In this real-life, largest-to-date analysis of IVL use to manage underexpanded stent, IVL proved to be an effective and safe method for facilitating stent expansion and increasing luminal gain.

Mitochondrial DNA copy number and trimethylamine levels in the blood: New insights on cardiovascular disease biomarkers.

Among cardiovascular disease (CVD) biomarkers, the mitochondrial DNA copy number (mtDNAcn) is a promising candidate. A growing attention has been also dedicated to trimethylamine-N-oxide (TMAO), an oxidative derivative of the gut metabolite trimethylamine (TMA). With the aim to identify biomarkers predictive of CVD, we investigated TMA, TMAO, and mtDNAcn in a population of 389 coronary artery disease (CAD) patients and 151 healthy controls, in association with established risk factors for CVD (sex, age, hypertension, smoking, diabetes, glomerular filtration rate [GFR]) and troponin, an established marker of CAD. MtDNAcn was significantly lower in CAD patients; it correlates with GFR and TMA, but not with TMAO. A biomarker including mtDNAcn, sex, and hypertension (but neither TMA nor TMAO) emerged as a good predictor of CAD. Our findings support the mtDNAcn as a promising plastic biomarker, useful to monitor the exposure to risk factors and the efficacy of preventive interventions for a personalized CAD risk reduction.

The non-invasive evaluation of heart function in patients with an acute myocardial infarction: The role of impedance cardiography.

BACKGROUND: The purpose of this study was to analyze hemodynamic changes in patients treated with percutaneous coronary intervention (PCI) at an early stage of acute myocardial infarction (AMI) and at 1-month follow-up. METHODS: Patients with AMI (n = 27) who underwent PCI were analyzed using impedance cardiography (ICG). ICG data were collected continuously (beat by beat) during the whole PCI procedure and thereafter at every 60 s for the next 24 h. Blood pressure was taken every 10 min and stored for analysis. Additionally the following parameters were measured: cardiac index (CI), stroke volume index (SVi), left cardiac work index (LCWi), contractility index (CTi), ventricular ejection time (VET), systemic vascular resistance index (SVRi), thoracic fluid content index (TFCi) and heart rate (HR). RESULTS: In the first 24 h after PCI all the contractility parameters including CI, SVi, LCWi, CTi and VET significantly decreased, whereas HR, SVRi and TFCi increased compared to baseline. All of the parameters examined got normalized at 1 month. The CI, SVi, LCWi, CTi, SVRi did not significantly differ from baseline, however the HR and VET were significantly lower compared to first day after PCI CONCLUSIONS: Cardiac performance deteriorates early after PCI and normalizes after 1 month in patients with an AMI. ICG is useful for hemodynamic monitoring of AMI patients during and after invasive therapy.

Trimethylamine N-oxide and the reverse cholesterol transport in cardiovascular disease: a cross-sectional study.

The early atherosclerotic lesions develop by the accumulation of arterial foam cells derived mainly from cholesterol-loaded macrophages. Therefore, cholesterol and cholesteryl ester transfer protein (CETP) have been considered as causative in atherosclerosis. Moreover, recent studies indicate the role of trimethylamine N-oxide (TMAO) in development of cardiovascular disease (CVD). The current study aimed to investigate the association between TMAO and CETP polymorphisms (rs12720922 and rs247616), previously identified as a genetic determinant of circulating CETP, in a population of coronary artery disease (CAD) patients (n = 394) and control subjects (n = 153). We also considered age, sex, trimethylamine (TMA) levels and glomerular filtration rate (GFR) as other factors that can potentially play a role in this complex picture. We found no association of TMAO with genetically determined CETP in a population of CAD patients and control subjects. Moreover, we noticed no differences between CAD patients and control subjects in plasma TMAO levels. On the contrary, lower levels of TMA in CAD patients respect to controls were observed. Our results indicated a significant correlation between GFR and TMAO, but not TMA. The debate whether TMAO can be a harmful, diagnostic or protective marker in CVD needs to be continued.

Gender-Related Differences in Trimethylamine and Oxidative Blood Biomarkers in Cardiovascular Disease Patients.

Gender differences in the burden of cardiovascular disease (CVD) have been observed worldwide. In this study, plasmatic levels of trimethylamine (TMA) and blood oxidative biomarkers have been evaluated in 358 men (89 controls and 269 CVD patients) and 189 women (64 control and 125 CVD patients). The fluorescence technique was applied to determine erythrocyte membrane fluidity using 1,6-diphenyl-1,3,5-hexatriene (DPH) and Laurdan, while lipid hydroperoxides were assessed by diphenyl-1-pyrenylphosphine (DPPP). Results show that levels of plasmatic TMA were higher in healthy men with respect to healthy women (p = 0.0001). Significantly lower TMA was observed in male CVD patients (0.609 ± 0.104 µM) compared to healthy male controls (0.680 ± 0.118 µM) (p < 0.001), while higher levels of TMA were measured in female CVD patients (0.595 ± 0.115 µM) with respect to female controls (0.529 ± 0.073 µM) (p < 0.001). DPPP was significantly higher in healthy control men than in women (p < 0.001). Male CVD patients displayed a lower value of DPPP (2777 ± 1924) compared to healthy controls (5528 ± 2222) (p < 0.001), while no significant changes were measured in females with or without CVD (p > 0.05). Membrane fluidity was significantly higher (p < 0.001) in the hydrophobic bilayer only in control male subjects. In conclusion, gender differences were observed in blood oxidative biomarkers, and DPPP value might be suggested as a biomarker predictive of CVD only in men.

Polyhedral erythrocytes in intracoronary thrombus and their association with reperfusion in myocardial infarction.

OBJECTIVE: The tightly packed arrays of polyhedral erythrocytes, polyhedrocytes, formed during thrombus contraction, have been detected in some intracoronary thrombi (ICT) obtained from patients with ST-segment elevation myocardial infarction (STEMI). We sought to investigate determinants of polyhedrocyte content in ICT and its association with reperfusion in STEMI. METHODS: We assessed the composition of ICT obtained during thrombectomy within 12 h since the symptom onset in 110 STEMI patients, following 300 mg of aspirin (n = 110) and 600 mg of clopidogrel (n = 75). The predominance of fibrin, erythrocytes, polyhedrocytes or platelets was evaluated using scanning electron microscopy. RESULTS: Polyhedrocytes were found in 34 (30.9%) ICT, in which they covered 20-50% (median 38.8%) fields of view. Patients with polyhedrocytes in ICT had lower median minimal reference infarct-related artery (IRA) diameter by 20% (p < 0.0001) and area by 31% (p < 0.0001) versus those without polyhedrocytes. Time of ischemia showed association with the polyhedrocyte content (r = 0.26, p = 0.007). By multivariate analysis, minimal IRA diameter (ß = - 0.50, p < 0.0001) and ischemia time (ß = 0.20, p = 0.035) independently affected polyhedrocyte content in ICT (R2 = 0.45, p < 0.0001). Patients with ischemia time of > 3 h and polyhedrocytes present in ICT had more frequently TIMI-2/3 flow after thrombus aspiration (96% vs. 67%, p = 0.02) and final TIMI-2/3 myocardial perfusion grade (92% vs. 57%, p = 0.044) versus those without polyhedrocytes. CONCLUSIONS: Our findings indicate that the presence of polyhedrocytes in ICT, observed in one-third of STEMI patients, is associated with smaller minimal IRA diameter, prolonged ischemia and their formation in late presenters is associated with more effective thrombus aspiration and better myocardial reperfusion.

Mast cell derived carboxypeptidase A3 is decreased among patients with advanced coronary artery disease.

BACKGROUND: Coronary artery disease (CAD) affects milions of people and can result in myocardial infarction (MI). Previously, mast cells (MC) have been extensively investigated in the context of hypersensitivity, however as regulators of the local inflammatory response they can potentially contribute to CAD and/or its progression. The aim of the study was to assess if serum concentration of MC proteases: carboxypeptidase A3, cathepsin G and chymase 1 is associated with the extension of CAD and MI. METHODS: The 44 patients with angiographically confirmed CAD (23 subjects with non-ST-segment elevation MI [NSTEMI] and 21 with stable CAD) were analyzed. Clinical data were obtained as well serum concentrations of carboxypeptidase A3, cathepsin G and chymase 1 were also measured. RESULTS: Patients with single vessel CAD had higher serum concentration of carboxypeptidase than those with more advanced CAD (3838.6 ± 1083.1 pg/mL vs. 2715.6 ± 442.5 pg/mL; p = 0.02). There were no significant differences in levels of any protease between patients with stable CAD and those with NSTEMI. Patients with hypertension had ≈2-fold lower serum levels of cathepsin G than normotensive individuals (4.6 ± 0.9 pg/mL vs. 9.4 ± 5.8 pg/mL; p = 0.001). Cathepsin G levels were also decreased in sera of the current smokers as compared with non-smokers (3.1 ± 1.2 ng/mL vs. 5.8 ± 1.2 ng/mL, p = 0.02). CONCLUSIONS: Decreased serum level of carboxypeptidase is a hallmark of more advanced CAD. Lower serum levels of carboxypeptidase A3 and catepsin G are associated with risk factors of blood vessel damage suggesting a protective role of these enzymes in CAD.

ScaI atrial natriuretic peptide gene polymorphisms and their possible association with postoperative atrial fibrillation - a preliminary report.

INTRODUCTION: Atrial fibrillation (AF) is a frequently encountered complication after coronary artery bypass grafting (CABG), but its underlying mechanisms are still unclear. The natriuretic peptides have been reported as markers for predicting the occurrence of postoperative AF. This study evaluates whether the ScaI ANP gene polymorphisms predict the occurrence of postoperative AF. MATERIAL AND METHODS: A prospective study of 203 consecutive patients with coronary artery disease undergoing elective CABG was undertaken for atrial natriuretic peptide (ANP) ScaI gene polymorphism. Several perioperative data were analysed. Postoperative AF was defined as lasting for at least 15 min, confirmed by 12-lead ECG and occurring within 6 postoperative days. The ScaI polymorphism of the ANP gene was determined by polymerase chain reaction (PCR). Size-dependent separation of the PCR products on a polyacrylamide gel was followed by staining with ethidium bromide. RESULTS: The total frequency of AF was 19.7%. The frequencies of ScaI ANP gene polymorphisms were as follows: A1A1 4.90%, A1A2 59.60% and A2A2 35.46%. In order to assess the hypothesis that the A2 allele is a marker of increased risk of postoperative atrial fibrillation, the odds ratio (OR) was calculated: A2 vs. non-A2, OR = 0.98 (0.23-4.1), p = 0.97, which was not significant. The odds ratios for A2A2 and A1A1 were not significant either: A2A2 vs. non-A2A2, OR = 1.11 (0.54-2.29), p = 0.76, and A1A1 vs. non-A1A1, OR = 1.17 (0.23-5.92), p = 0.84. CONCLUSIONS: ANP genotype did not predispose to the incidence of "new-onset" AF.

Periprocedural Myocardial Injury After Recanalization of Single Chronic Coronary Occlusion - A Propensity Score Analysis Comparing Long-Term Clinical Outcomes.

BACKGROUND: Rates and importance of periprocedural myocardial injury (PMI) after crossing coronary chronic total occlusions (CTOs) is not well understood. This study sought to investigate long-term clinical implications of PMI in patients undergoing percutaneous coronary intervention (PCI) for single CTO utilizing antegrade technique. METHODS: Out of 11,957 patients undergoing non-urgent PCI, a total of 1110 patients with symptomatic angina and single CTO were treated by antegrade PCI and observed for up to 10 years. The primary objective included cardiac death, while the secondary aim comprised all major adverse cardiovascular and cerebrovascular event (MACCE) rate. RESULTS: Troponin-defined PMI occurred in 4.7% patients (n = 52). At 1 year, the cardiac death and MACCE rates were significantly higher in patients with vs without PMI (hazard ratio [HR], 5.72; 95% confidence interval [CI], 1.59-20.49; P=.01; HR, 1.84; 95% CI, 1.07-3.18; P=.03, respectively). At long-term follow-up, patients with PMI had a trend toward a higher incidence of cardiac death than patients without PMI (HR, 2.51; 95% CI, 0.99-6.33; P=.05) and no differences were demonstrated in terms of overall MACCE between both groups (HR, 1.19; 95% CI, 0.73-1.93; P=.49). After propensity score adjustment, no significant differences were observed regarding the short-term and long-term outcomes. CONCLUSION: CTO-PCI is a safe procedure if routinely performed in symptomatic patients at a high-volume center. PMI does not influence long-term outcomes after antegrade CTO-PCI.

Atrial fibrillation following off-pump versus on-pump coronary artery bypass grafting: Incidence and risk factors.

BACKGROUND: Postoperative atrial fibrillation (AF) is a common arrhythmia that occurs after coronary artery bypass grafting (CABG). New surgical techniques, particularly off-pump coronary artery bypass (OPCAB), are thought to be less invasive and results in fewer complications, i.e. AF, but available data are inconsistent. The aim of this study is to present the incidence and risk factors of AF in patients operated on with or without cardiopulmonary bypass. METHODS: We studied 1836 consecutive patients with stable coronary artery disease who were operated on with (CABG) or without (OPCAB) cardiopulmonary bypass. The patients were monitored using a continuous electrocardiogram monitoring system until the sixth postoperative day. RESULTS: Atrial fibrillation occurred in 18.3% and 19.3% of CABG and OPCAB patients, respectively (p = 0.3). The peak incidence of arrhythmia was observed between the second and third postoperative day in both CABG and OPCAB patients (36% and 41%, respectively). Patient's age and history of hypertension were significant predictors of postoperative AF (OR 1.38, 95% CI 1.01-1.76, p = 0.0002; and OR 1.38, 95% CI 1.01-1.76, p = 0.008, respectively). Patients who developed AF vs. without AF had significantly higher rates of complications such as death (3.1% vs. 1.2%, p = 0.01), reoperation (5.2% vs. 2.8%, p = 0.02), and the need to utilize intra-aortic balloon pump (IABP) (6.8% vs. 3.4%, p = 0.002). Use of IABP and reoperation were significant perioperative predictors of the arrhythmia (OR 2.1, 95% CI 1.27-3.4, p = 0.003; and OR 1.9, 95% CI 1.09-3.30, p = 0.02, respectively). AF was also associated with a prolonged stay in an intensive care unit (72.5 ± 78.8 for patients with AF vs. 34.6 ± 25.2 for patients with sinus rhythm, p = 0.000001). CONCLUSIONS: In patients undergoing CABG, postoperative AF is a common arrhythmia independent of the type of surgical procedure.

Elevated Serum Tryptase and Endothelin in Patients with ST Segment Elevation Myocardial Infarction: Preliminary Report.

UNLABELLED: An inflammatory response plays a crucial role in myocardial damage after an acute myocardial infarction. OBJECTIVES: To measure serum concentrations of several mediators in patients with an acute myocardial infarction (STEMI) and to assess their potential relationship with a risk of coronary instability. PATIENTS AND METHODS: The 33 patients with STEMI and 19 healthy volunteers were analyzed. The clinical data were obtained; as well serum concentrations of tryptase, endothelin (ET-1), angiogenin, soluble c-kit, and PDGF were measured. RESULTS: Patients with STEMI had higher serum tryptase and ET-1 than healthy volunteers (2,5 ± 0,4 ng/mL versus 1,1 ± 0,4 ng/mL and 0,7 ± 0,1 ng/mL versus 0,3 ± 0,1 ng/mL, resp.). Subjects with significant lesion in left anterior descending artery (LAD) had lower serum ET-1 compared to those with normal LAD (0,6 ± 0,2 pg/mL versus 0,9 ± 0,4 pg/mL). Patients with three-vessel coronary artery disease (CAD) had higher level of soluble c-kit compared to those with one- or two-vessel CAD: 19,9 ± 24,1 ng/mL versus 5,6 ± 1,9 ng/mL. CONCLUSIONS: Elevated serum tryptase and ET-1 may be markers of increased coronary instability; some cytokines may be related to the extension of CAD.

Successful versus unsuccessful antegrade recanalization of single chronic coronary occlusion: eight-year experience and outcomes by a propensity score ascertainment.

AIMS: The effectiveness of revascularization of chronic total occlusion (CTO) remains intriguing. Thus, we sought to investigate whether a successful PCI for single CTO improves outcomes in a setting of stable angina and chronic occlusion of single coronary artery. METHODS AND RESULTS: Of 11 957 consecutive patients referred for nonurgent PCI between 2003 and 2010, 1110 displayed single CTO and were enrolled to the central CTO-registry database. The primary end-point included all-cause mortality, the secondary end-point a composite of safety outcome measure of all-cause death, nonfatal-MI, the need for urgent revascularization and stroke. The major adverse cardiovascular event (MACE) records were extracted from the national administrative database and all patients were linked to the long-term follow-up. Since the patient assignment was not random, we performed the propensity scoring to minimize selection bias; 734 patients (66%) had a successful PCI-CTO. Compared with successful procedures, unsuccessful procedures had similar rates of all-cause death both in crude (HR, 0.78; 95%CI, 0.49-1.25; P = 0.30) and adjusted analysis (HR, 0.80; 95%CI, 0.50-1.28; P = 0.34). A similar, significant reduction in overall MACE was noted with successful PCI-CTO compared with unsuccessful procedure in unadjusted (HR, 0.74; 95%CI, 0.56-0.96; P = 0.020) and adjusted calculation (HR, 0.73; 95%CI, 0.56-0.96; P = 0.019). Patients after successful PCI-CTO as compared with failed recanalization less frequently underwent surgical revascularization. The benefit was sustained at 3 years follow-up. CONCLUSIONS: Successful PCI for single CTO does not improve long-term survival, nonetheless, is associated with reduced overall MACE and the need for surgical revascularization.

Successful recanalisation of isolated chronic total occlusions improves outcomes in long-term observation: a case-control study.

BACKGROUND AND AIM: The long-term benefit of percutaneous recanalisation of chronic total occlusion (CTO) is still unclear. Given advances in interventional cardiology over the last two decades, we sought to investigate whether a successful percutaneous coronary intervention for CTO (PCI-CTO) improves outcomes in an age- and gender-matched single-centre cohort of stable angina patients. METHODS: Out of 401 consecutive patients enrolled to the CTO-Registry database, 276 patients were included in the final analysis. Patients with unsuccessful PCI-CTO (n = 138) were age- and gender-matched in a 1:1 ratio with patients who underwent a successful procedure. The primary end-points included hard end-points comprising death and nonfatal myocardial infarction (MI) and a composite safety outcome measure of death, nonfatal MI and ischaemia-driven revascularisation. The secondary end-point was improvement in angina status or complete resolution of angina symptoms. Patients were followed up for six months and at two years. RESULTS: Patients who underwent a successful recanalisation of CTO, compared to those who underwent an unsuccessful procedure, revealed similar rates of composite death and MI at six months (0.7% vs. 1.4%; hazard ratio [HR], 0.50; 95% confidence interval ratio [CI], 0.05-4.80; p = 0.56) and two years (1.4% vs. 5.8%; HR 0.24; 95% CI 0.07-0.85; p = 0.053). A significant difference in composite safety end-points between subsets, although not recorded after six months of observation (8.7% vs. 15.2%; HR 0.54; 95% CI 0.27-1.07; p = 0.095), was noted at two years follow-up (15.2% vs. 29.7%; HR 0.47; 95% CI 0.29-0.77; p = 0.004). A greater improvement in symptom burden or resolution of angina symptoms was documented after a successful PCI at both six months (68.1% vs. 23.2%, p < 0.001; 80.4% vs. 34.8%, p < 0.001, respectively) and two years (52.2% and 8.0%, p < 0.001; 68.1% vs. 22.5%, p < 0.001, respectively). CONCLUSIONS: Successful recanalisation of CTO improves outcomes in long-term observation.

Major adverse cardiovascular events after drug-eluting stent implantation in patients with single chronic total occlusion: a single-center registry.

BACKGROUND: There are limited data on the long-term safety and efficacy of drug-eluting stents (DES) implantation in patients with stable angina referred for elective percutaneous coronary intervention (PCI) of chronic total occlusion (CTO). We therefore aim to investigate whether DES compared with bare-metal stent (BMS) implantation improves long-term outcomes after successful recanalization of single CTO. METHODS: A total of 345 consecutive patients who underwent successful recanalization of single CTO and received DES or BMS in the Cardioangiology Laboratories of the Medical University of Gdansk between January 1, 2006 and December 31, 2010 were included in the CTO Registry database. We compared the 1-year and long-term clinical outcomes of 137 consecutive patients who underwent PCI for CTO and DES implantation with outcomes of 208 patients after successful CTO treatment with BMS implantation. The median follow-up was 22.6 ± 3 months (21.0 ± 3.9 months for DES vs 23.6 ± 1.5 months for BMS; P<.001). The primary endpoints included a composite of all-cause death and non-fatal myocardial infarction (MI) and composite safety endpoint of major adverse cardiovascular events (MACEs), including death, MI and symptom-driven target lesion revascularization (TLR). A secondary endpoint was a symptom-driven TLR. RESULTS: After stent implantation we noted lower rates of the composite endpoint at 1-year (9.5% DES vs 18.3% BMS; P=.01) and long-term follow-up (11.7% DES vs 21.1% BMS; P=.02) due to fewer episodes of TLR in the DES group (5.1% DES vs 14.4% BMS; P=.006 at 1-year follow-up; 7.3% DES vs 14.4% BMS; P=.04 at long-term follow-up). No significant differences were documented in the rate of death, MI, or in-stent thrombosis between investigated subsets. After adjusting for patient and procedural characteristics as well as propensity, BMS implantation remained independently associated with an increased hazard of 1-year MACE (adjusted hazard ratio [AHR], 2.09; 95% confidence interval [CI], 1.2-3.64; P=.005) and long-term MACEs (AHR, 1.99; 95% CI, 1.18-3.38; P<.01). CONCLUSIONS: DES implantation during PCI for single CTO reduces MACE rate at 1-year and long-term follow-up due to the significant reduction of TLR in the DES group. Therefore, DES implantation should be preferred as an optimal treatment strategy of single CTO in stable angina patients.

[Catastrophic antiphospholipid syndrome complicated by cardiogenic shock - a case report]. / Katastroficzny zespól antyfosfolipidowy przebiegajacy ze wstrzasem kardiogennym - opis przypadku.

A case of a 29-year-old woman 18 days after delivery with catastrophic antiphospholipid syndrome secondary (CAPS) due to undiagnosed systemic lupus erythematosus, leading to cardiogenic shock is reported. Laboratory evaluation revealed increased anticardiolipin antibodies, lupus anticoagulant, antinuclear antibody and thrombocytopenia. Left ventricular ejection fraction was 20%, neurologic deficit and acute renal failure were also present. Cardiac involvement is common in CAPS, but cardiomyopathy due to microvascular thrombosis is rare. CAPS should be considered as a cause of acute heart failure in a women with systemic lupus erythematosus. In the presented case early therapy with anticoagulants, steroids, immunoglobulins and plasmaferesis was beneficial.