Antti Ylitalo

Randomized Study on Simple Versus Complex Stenting of Coronary Artery Bifurcation Lesions: The Nordic Bifurcation Study

Background— The optimal stenting strategy in coronary artery bifurcation lesions is unknown. In the present study, a strategy of stenting both the main vessel and the side branch (MV+SB) was compared with a strategy of stenting the main vessel only, with optional stenting of the side branch (MV), with sirolimus-eluting stents. Methods and Results— A total of 413 patients with a bifurcation lesion were randomized. The primary end point was a major adverse cardiac event: cardiac death, myocardial infarction, target-vessel revascularization, or stent thrombosis after 6 months. At 6 months, there were no significant differences in rates of major adverse cardiac events between the groups (MV+SB 3.4%, MV 2.9%; P=NS). In the MV+SB group, there were significantly longer procedure and fluoroscopy times, higher contrast volumes, and higher rates of procedure-related increases in biomarkers of myocardial injury. A total of 307 patients had a quantitative coronary assessment at the index procedure and after 8 months. The combined angiographic end point of diameter stenosis >50% of main vessel and occlusion of the side branch after 8 months was found in 5.3% in the MV group and 5.1% in the MV+SB group (P=NS). Conclusions— Independent of stenting strategy, excellent clinical and angiographic results were obtained with percutaneous treatment of de novo coronary artery bifurcation lesions with sirolimus-eluting stents. The simple stenting strategy used in the MV group was associated with reduced procedure and fluoroscopy times and lower rates of procedure-related biomarker elevation. Therefore, this strategy can be recommended as the routine bifurcation stenting technique.

Heart rate variability in systemic hypertension

Low heart rate (HR) variability is a risk factor for cardiac mortality in various patient populations, but it has not been well established whether patients with long-standing hypertension have abnormalities in the autonomic modulation of HR. Time and frequency domain measures of HR variability were compared in randomly selected, age-matched populations of 188 normotensive and 168 hypertensive males (mean age 50 +/- 6 years for both). The standard deviation of the RR intervals was lower in the hypertensive subjects than in the normotensive ones (52 +/- 19 vs 59 +/- 20 mss; p <0.01), and the very low and low-frequency spectral components of HR variability analyzed as absolute units were reduced in the hypertensive patients relative to the normotensive controls (p <0.001 for both). Hypertensive subjects also had blunted changes of the normalized low- and high-frequency components in response to an upright (sitting) posture (NS) as compared with normotensive subjects (p <0.001 for both). Multiple regression analysis showed the standard deviation of the RR intervals to be predicted most strongly by systolic blood pressure, both in the patients with hypertension (beta--0.20, p=0.01) and in the normotensive subjects (beta--0.28, p=0.0002). After adjustment for the baseline differences in blood pressure and body mass index, none of the absolute measures of the HR variability or the responses of the normalized units of HR variability to a change in the body posture differed between the hypertensive subjects and normotensive controls. These data show that long-standing hypertension results in reduced overall HR variability and blunted autonomic responses to a change in body posture. Altered autonomic modulation of HR in hypertension is mainly due to elevated blood pressure and obesity in males with long-standing hypertension as compared with normotensive subjects.

Thromboembolic complications after cardioversion of acute atrial fibrillation: the FinCV (Finnish CardioVersion) study.

OBJECTIVES This study sought to explore the incidence and risk factors of thromboembolic complications after cardioversion of acute atrial fibrillation. BACKGROUND Anticoagulation therapy is currently recommended after cardioversion of acute atrial fibrillation in patients with risk factors for stroke, but the implementation of these new consensus-based guidelines has been slow. METHODS A total of 7,660 cardioversions were performed in 3,143 consecutive patients with atrial fibrillation lasting <48 h in 3 hospitals. For this analysis, embolic complications were evaluated during the 30 days after 5,116 successful cardioversions in 2,481 patients with neither oral anticoagulation nor peri-procedural heparin therapy. RESULTS There were 38 (0.7%; 95% confidence interval [CI]: 0.5% to 1.0%) definite thromboembolic events (31 strokes) within 30 days (median 2 days, mean 4.6 days) after cardioversion. In addition, 4 patients suffered transient ischemic attack after cardioversion. Age (odds ratio [OR]: 1.05; 95% CI: 1.02 to 1.08), female sex (OR: 2.1; 95% CI: 1.1 to 4.0), heart failure (OR: 2.9; 95% CI: 1.1 to 7.2), and diabetes (OR: 2.3; 95% CI: 1.1 to 4.9) were the independent predictors of definite embolic events. Classification tree analysis showed that the highest risk of thromboembolism (9.8%) was observed among patients with heart failure and diabetes, whereas patients with no heart failure and age <60 years had the lowest risk of thromboembolism (0.2%). CONCLUSIONS The incidence of post-cardioversion thromboembolic complications is high in certain subgroups of patients when no anticoagulation is used after cardioversion of acute atrial fibrillation. (Safety of Cardioversion of Acute Atrial Fibrillation [FinCV]; NCT01380574).

Safety of percutaneous coronary intervention during uninterrupted oral anticoagulant treatment

AIMS Uninterrupted anticoagulation (UAC) is assumed to increase bleeding and access-site complications. A common consensus is to postpone percutaneous coronary interventions (PCI) to reach international normalized ratio (INR) levels < 1.5-1.8. METHODS AND RESULTS To assess the safety and feasibility of UAC, we analysed retrospectively all consecutive patients (n = 523) on warfarin therapy referred for PCI in four centres with a policy to interrupt anticoagulation (IAC) before PCI and in three centres with a long experience on UAC during PCI. Major bleeding, access-site complications, and major adverse cardiac events (death, myocardial infarction, target vessel revascularization, and stent thrombosis) were recorded during hospitalization. In the IAC group, warfarin was withdrawn for a mean of 3 days prior to PCI (mean INR 1.7). In the UAC group, mean INR value was 2.2. Glycoprotein IIb/IIIa (GP) inhibitors (P < 0.001) and low-molecular-weight heparins (P < 0.001) were more often used in the IAC group. Major bleeding and access-site complications were more common in the IAC group (5.0% vs. 1.2%, P = 0.02 and 11.3% vs. 5.0%, P = 0.01, respectively) than in the UAC group. After adjusting for propensity score, the group difference in access-site complications remained significant [OR (odds ratio) 2.8, 95% CI (confidence interval) 1.3-6.1, P = 0.008], but did not remain significant in major bleeding (OR 3.9, 95% CI 1.0-15.3, P = 0.05). In multivariable analysis, femoral access (OR 9.9, 95% CI 1.3-75.2), use of access-site closure devices (OR 2.1, 95% CI 1.1-4.0), low-molecular-weight heparin (OR 2.7, 95% CI 1.1-6.7) and old age predicted access-site complications, and the use of GP inhibitors (OR 3.0, 95% CI 1.0-9.1) remained as a predictor of major bleeding. CONCLUSION Our study shows that PCI is a safe procedure during UAC with no excess bleeding complications.

Safety in simple versus complex stenting of coronary artery bifurcation lesions. The Nordic Bifurcation Study 14-month follow-up results

AIMS The risk of stent thrombosis has been reported to increase with percutaneous coronary intervention (PCI) complexity. The present study reports the pre-specified secondary endpoint of a 14-month stent thrombosis and major adverse cardiac events in patients stented with a simple versus a complex bifurcation technique using sirolimus eluting stents (SES). METHODS AND RESULTS A total of 413 patients with a coronary bifurcation lesion were randomised to a simple treatment strategy; stenting of main vessel and optional stenting of side branch (MV group), or to a complex stenting strategy; stenting of both main vessel and side branch (MV+SB group). Mortality data were available in all patients and 14-month clinical follow-up data in 395 (96%) of the patients. After 14 months, the rates of definite, probable and possible stent thrombosis (ARC criteria) were 1.0% vs. 0.5%, 1.0% vs. 0% and 0.5% vs. 0% (ns) in the MV and in the MV+SB groups, respectively. Rates of MACE were 9.5% in the MV group and 8.2% in the MV+SB group (ns). Total death was seen in 2.4% vs. 1.0% and non-PCI related myocardial infarction in 2.0% vs. 1.0% in the MV and the MV+SB groups, respectively. CONCLUSIONS After 14 months, two months after recommended cessation of dual antiplatelet therapy, the rates of stent thrombosis and major adverse cardiac events were low and independent of treatment complexity in patients treated with SES for coronary artery bifurcation lesions.

Baroreflex sensitivity and variants of the renin angiotensin system genes

OBJECTIVES Because the renin-angiotensin-aldosterone system (RAS) modifies cardiovascular autonomic regulation, we studied the possible associations between baroreflex sensitivity (BRS) and polymorphism in the RAS genes. BACKGROUND Wide intersubject variability in BRS is not well explained by cardiovascular risk factors or life style, suggesting a genetic component responsible for the variation of BRS. METHODS Baroreflex sensitivity as measured from the overshoot phase of the Valsalva maneuver and genetic polymorphisms were examined in a random sample of 161 women and 154 men aged 41 to 61 years and then in an independent random cohort of 29 men and 37 women aged 36 to 37 years. An insertion/deletion (I/D) polymorphism of angiotensin-converting enzyme (ACE), M235T variants of angiotensinogen (AGT) and two diallelic polymorphisms in the gene encoding aldosterone synthase (CYP11B2), one in the promoter (-344C/T) and the other in the second intron, were identified by polymerase chain reaction. RESULTS In the older population, BRS differed significantly across CYP11B2 genotype groups in women (10.1 +/- 4.5, 8.7 +/- 3.8 and 7.1 +/- 3.2 ms x mm Hg(-1) in genotypes -344TT, CT and CC, respectively, p = 0.003 and 11.1 +/- 4.4, 8.9 +/- 4.1 and 7.5 +/- 3.4 ms x mm Hg(-1) in intron 2 genotypes 1/1, 1/2 and 2/2, respectively, p = 0.002), but not in men. No comparable associations were found for BRS with the I/D polymorphism of ACE or the M235T variant of AGT. In the younger population, BRS was even more strongly related to the CYP11B2 promoter genotype (p = 0.0003). The association was statistically significant both in men (p = 0.015) and in women (p = 0.03). CONCLUSIONS Common genetic polymorphisms in the aldosterone synthase (CYP11B2) gene is associated with interindividual variation in BRS.

Safety of Diagnostic Coronary Angiography During Uninterrupted Therapeutic Warfarin Treatment

Long-term warfarin therapy is assumed to increase bleeding and access site complications after coronary angiography and it is often recommended to postpone invasive procedures to reach international normalized ratio (INR) levels <1.8. To assess the safety and feasibility of diagnostic coronary angiography during uninterrupted warfarin therapy, we retrospectively analyzed all consecutive patients (n = 258) on warfarin therapy referred for diagnostic coronary angiography in 2 centers with long experience in uninterrupted warfarin therapy during coronary angiography and in 1 center with a policy of preprocedural warfarin pause. An age- and gender-matched control group (n = 258) with similar disease presentation (unstable or stable symptoms) was collected from each center. Radial access was used in 56% of patients in the warfarin group and in 60% of controls (p = 0.21). There was no difference in access site and bleeding complications (1.9% vs 1.6%) or major adverse cardiovascular and cerebrovascular events (0.4% vs 0.8%) between the warfarin group and their controls. Warfarin was interrupted in 80 patients (31%), and bridging therapy was used in 24 of these patients (30%). INR levels were higher in the uninterrupted warfarin group (2.3 vs 1.9, p <0.001), but the incidence of access site complications was not higher (1.7%) than in patients (n = 80) with a warfarin pause (2.5%) or in patients with pause and bridging therapy (8.3%). Need for blood transfusions (n = 2) occurred only in patients with bridging therapy. Access site complications were more common in the 22 patients with supratherapeutic anticoagulation (INR >3) than in patients with therapeutic periprocedural INR (9.1% vs 1.5%, p <0.05). In conclusion, a simple strategy of performing coronary angiography during uninterrupted therapeutic warfarin anticoagulation is a tempting alternative to bridging therapy and is likely to lead to considerable cost savings.

Effects of combination antihypertensive therapy on baroreflex sensitivity and heart rate variability in systemic hypertension

Earlier studies have shown that cardiovascular autonomic regulation is impaired in untreated or poorly controlled systemic hypertension. The purpose of this double-blind, randomized parallel trial was to evaluate whether improved blood pressure (BP) control can reverse this impairment. The study group consisted of 33 patients (age 45 to 63 years) with poor BP control who received randomized metoprolol or enalapril monotherapy. Baroreflex sensitivity (BRS) was assessed by phenylephrine test and time- and frequency-domain measurements of heart rate variability (HRV) were analyzed from 24-hour ambulatory electrocardiographic recordings during monotherapy and after 10 weeks of combination therapy with metoprolol + felodipine or enalaril + hydrochlorothiazide to lower casual BP to < 140/90 mm Hg. Intensified treatment decreased 24-hour systolic and diastolic BP from 139 +/- 12/86 +/- 8 mm Hg to 126 +/- 8/80 +/- 7 mm Hg (p <0.0001). BRS improved from 6.2 +/- 3.2 ms/mm Hg to 8.9 +/- 4.1 ms/mm Hg (p <0.0001) and measurements of HRV (e.g., SD of all RR intervals from 128 +/- 45 ms to 145 +/- 46 ms, p <0.001) improved significantly during the combination therapy. Changes in BRS and HRV were similar in magnitude in both treatment arms. Mean RR intervals were comparable before and after intensive antihypertensive therapy (850 +/- 124 ms vs 937 +/- 279 ms, p = NS). These data indicate that adequate BP control with modem antihypertensive combination therapy can improve cardiovascular autonomic function, which may partially explain the reduced cardiac mortality observed in patients with intensified antihypertensive therapy.

Bacterial Signatures in Thrombus Aspirates of Patients With Myocardial Infarction

Background— Infectious agents, especially bacteria and their components originating from the oral cavity or respiratory tract, have been suggested to contribute to inflammation in the coronary plaque, leading to rupture and the subsequent development of coronary thrombus. We aimed to measure bacterial DNA in thrombus aspirates of patients with ST-segment–elevation myocardial infarction and to check for a possible association between bacteria findings and oral pathology in the same cohort. Methods and Results— Thrombus aspirates and arterial blood from patients with ST-segment–elevation myocardial infarction undergoing primary percutaneous coronary intervention (n=101; 76% male; mean age, 63.3 years) were analyzed with real-time quantitative polymerase chain reaction with specific primers and probes to detect bacterial DNA from several oral species and Chlamydia pneumoniae. The median value for the total amount of bacterial DNA in thrombi was 16 times higher than that found in their blood samples. Bacterial DNA typical for endodontic infection, mainly oral viridans streptococci, was measured in 78.2% of thrombi, and periodontal pathogens were measured in 34.7%. Bacteria-like structures were detected by transmission electron microscopy in all 9 thrombus samples analyzed; whole bacteria were detected in 3 of 9 cases. Monocyte/macrophage markers for bacteria recognition (CD14) and inflammation (CD68) were detected in thrombi (8 of 8) by immunohistochemistry. Among the subgroup of 30 patients with myocardial infarction examined by panoramic tomography, a significant association between the presence of periapical abscesses and oral viridans streptococci DNA–positive thrombi was found (odds ratio, 13.2; 95% confidence interval, 2.11–82.5; P=0.004). Conclusions— Dental infection and oral bacteria, especially viridans streptococci, may be associated with the development of acute coronary thrombosis.

A prospective randomised comparison of titanium-nitride- oxide-coated bioactive stents with everolimus-eluting stents in acute coronary syndrome: the BASE-ACS trial

AIMS Titanium-nitride-oxide-coated bioactive stents (BAS) have demonstrated a favourable outcome when compared with paclitaxel-eluting stents in patients with acute myocardial infarction (MI). In a prospective randomised non-inferiority study design, we compared the safety and efficacy of BAS versus everolimus-eluting stents (EES) in patients with acute coronary syndrome (ACS). METHODS AND RESULTS We randomised 827 patients with ACS (1:1) to either BAS (417) or EES (410). The primary endpoint was a composite of cardiac death, non-fatal MI or ischaemia-driven target lesion revascularisation (TLR) at 12-month follow-up. Analyses were performed by intention to treat. At 12-month follow-up, the primary composite endpoint occurred in 9.6% of patients in the BAS group and 9.0% of those in the EES group (HR [hazard ratio] 1.04, 95% CI [confidence interval] 0.81-1.32, p=0.81, p for non-inferiority =0.001). Non-fatal MI was significantly less frequent in the BAS as compared with the EES group (2.2% vs. 5.9%, p=0.007). However, the individual rates of cardiac death and ischaemia-driven TLR were similar between the two groups (1.9% vs. 1.0%, p=0.39, and 6.5% vs. 4.9%, p=0.37, respectively). CONCLUSIONS In patients presenting with ACS, BAS achieved a clinical outcome that was non-inferior to EES at 12-month follow-up.