High-potency statin and ezetimibe use and mortality in survivors of an acute myocardial infarction: a population-based study.

OBJECTIVE: To determine all-cause mortality in patients with a first myocardial infarct who were treated with simvastatin compared with high-potency statin and simvastatin/ezetimibe combination. BACKGROUND: Despite statin use, residual cardiovascular risk remains. Therapeutic options include more potent statins or addition of ezetimibe. There is no clinical outcome data on the use of ezetimibe in such patients. METHODS: Retrospective longitudinal study using the United Kingdom General Practice Research Database. Patients who had survived 30 days after their first acute myocardial infarct (AMI), had not received prior statin or ezetimibe therapy and were started on a statin within 30 days of AMI were included. Three groups were identified according to their follow-up: (i) simvastatin monotherapy; (ii) high-potency statin group (patients who started on simvastatin and switched to atorvastatin or rosuvastatin); and (iii) ezetimibe/statin combination group (patients who received ezetimibe in addition to statin). RESULTS: 9597 patients (57% male, mean age of 65 ± 13 years) matched study criteria: simvastatin (n=6990 (72.8%)); high-potency statin (n=1883, (19.6%)); and ezetimibe/statin combination (n=724 (7.5%)). During a mean follow-up of 3.2 years, there were 1134 (12%) deaths. In the multivariate proportional hazards model, the adjusted HR for high-potency statin and ezetimibe group were 0.72 (95% CI 0.59 to 0.88, p<0.001) and 0.96 (95% CI 0.64 to 1.43, p=0.85), respectively. A similar result was also obtained in the propensity score analysis that took into account covariates that predicted drug treatment groups. CONCLUSIONS: Patients switched to a high-potency statin had a significantly reduced mortality compared with simvastatin monotherapy. There was no observed mortality benefit in the ezetimibe group.

A stepwise approach to the management of postinfarct ventricular tachycardia using catheter ablation as the first-line treatment: a single-center experience.

BACKGROUND: The occurrence of ventricular tachycardia (VT) after myocardial infarction is associated with poorer prognosis. In such patients, implantable cardioverter-defibrillators are recommended. Catheter ablation of VT is currently recommended only as an adjunctive therapy. Whether a successful VT ablation alone might be a viable strategy in some of these patients, however, remains unknown. The aim of the present study was to evaluate this strategy. METHODS AND RESULTS: Between January 2002 and December 2011, 189 patients with cardiomyopathy underwent 259 VT ablations in our center. Forty-five patients (mean age, 65.2±9.6 years; 91% men) with a history of myocardial infarction and mean left ventricular ejection fraction of 39.7±9.7% matched the study criteria and were included in this analysis. Acute success was obtained in 40 of 45 patients (88.9%). During a follow-up, on the basis of our stepwise algorithm (using acute success, repeat electrophysiological study, and recurrence of VT), 19 of 45 patients (42.2%) underwent implantable cardioverter-defibrillators implantation. During a median follow-up of 4.5 (interquartile range, 2.1-7.0) years, all-cause mortality occurred in 14 of 45 patients (31.1%). Using multivariate Cox regression analysis, age (hazard ratio, 1.13; 95% confidence interval, 1.03-1.22; P=0.007) was the only independent predictor of mortality, whereas implantable cardioverter-defibrillators implantation was not (hazard ratio, 0.54; 95% confidence interval, 0.18-1.64; P=0.28) CONCLUSIONS: Our results suggest that a stepwise approach to the management of VT with ablation as a first-line treatment in postinfarct patients presenting with VT might be a reasonable option. Further studies are required to confirm these results.

Age-related prognosis of syncope associated with a preexcitation syndrome.

BACKGROUND: Syncope in Wolff-Parkinson-White syndrome (WPW) is without relationship with WPW or reveals a poorly tolerated arrhythmia. Electrophysiologic study (EPS) is recommended. The purpose of the study was to evaluate the influence of the patient's age on the causes and prognosis of syncope. METHODS: A total of 98 patients, mean age 35 ± 18 years, with WPW were admitted for syncope. Note that 29 were aged between 9 and 19 years (mean 15 ± 3) (children and teenagers/group I), 45 between 20 and 49 years (mean 34 ± 8) (adults/group II), and 24 between 50 and 70 years (mean 60 ± 8) (elderly/group III). EPS consisted of atrial pacing and programmed atrial stimulation in control state and after isoproterenol. RESULTS: Potentially malignant form (rapid conduction in accessory pathway >240 beats/min in control state or >300 beats/min after isoproterenol and atrial fibrillation [AF] induction) was more frequent in group I (34%) than in groups II (7%) (P < 0.002) and III (0%) (P < 0.001). Orthodromic atrioventricular reentrant tachycardia (AVRT) and AF were induced as frequently in groups I (59, 34%), II (47, 15.5%), and III (54, 17%). AVRT was induced in all but one patient with malignant form. EPS was as frequently negative in groups I (27.5%), II (44%), and III (37.5%). Natural follow-up (mean 8 ± 6 years) indicated a favorable prognosis, only related to AVRT induction. Induced AF was without significance. CONCLUSIONS: Data in syncope and WPW syndrome depended on age: electrophysiological malignant form was frequent in children/teenagers, rare in adults, and absent in elderly. AVRT, the main cause of syncope, was as frequent in all ranges of age. AF's induction alone had no significance. Final prognosis was favorable.

Cycle length characteristics differentiating non-sustained from self-terminating ventricular fibrillation in Brugada syndrome.

AIMS: Limited information is available on self-terminating (ST) ventricular fibrillation (VF). Understanding spontaneous fluctuations in VF cycle length (CL) is required to identify arrhythmia that will stop before shock. Using Brugada syndrome (BS) as a model, the purpose of the study was to compare ST-VF and VF terminated by electrical shock and to look for spontaneous fluctuations in ventricular CL. METHODS AND RESULTS: Occurrence of ST-VF and VF was studied in 53 patients with 46 VF episodes: (i) spontaneously, (ii) during defibrillation threshold testing, (iii) during programmed ventricular stimulation (PVS). Fifteen presented ST-VF (average duration 25 s): 11 during PVS, 1 during defibrillation threshold testing, and 3 spontaneously (at device interrogation). Self-terminating ventricular fibrillation was compared with 31 VFs terminated by electrical shock. Mean ventricular CL was longer (192.5 ± 22 vs. 149 ± 19 ms) (P < 0.0001) and CL became longer or did not change in ST-VF (187 ± 28 vs. 200 ± 25 ms) (first vs. last CL)(NS) in contrast with progressively shorter CL in electrical shock-terminated VF (177 ± 14.5 vs. 139 ± 12 ms) (first vs. last CL before electrical shock) (P < 0.0001). Ventricular fibrillation had more CL variability (average 16.4 ± 6.5 ms) for the first 50 beats than ST-VF (average 4.08 ± 2) (P < 0.0001). Cycle length range for the first 50 beats was 9.6 ± 1 ms for ST-VF and 44 ± 15 for VF (P < 0.002). CONCLUSION: Self-terminating ventricular fibrillation in BS was not rare (28%). Ventricular CL was longer and progressively increased or did not change in ST-VF compared with electrical shock-terminating VF. Cycle length variability and CL range could differentiate VF and ST-VF within the first 50 beats. These parameters should be considered in the algorithms for VF detection and termination.

Is isoproterenol really required during electrophysiological study in patients with Wolff-Parkinson-White syndrome?

UNLABELLED: We have studied the results of electrophysiological study (EPS) in patients with Wolff-Parkinson-White syndrome (WPW) and spontaneous adverse clinical presentation and determined whether isoproterenol added incremental value. METHODS: EPS was performed in 63 patients with WPW and adverse clinical presentation at baseline. EPS was repeated after infusion of isoproterenol in 37 patients, including 25 without criteria for a malignant form at baseline. RESULTS: Atrioventricular orthodromic tachycardia was induced 44%, antidromic tachycardia in 11%, atrial fibrillation (AF) in 68% at baseline. At baseline EPS, criteria for a malignant form (AF induction and shortest CL <250 ms) were noted in 60%; tachycardia was not inducible in 16%. All the patients met the criteria for a malignant form after isoproterenol. CONCLUSIONS: EPS at baseline missed 16% of patients at risk of life-threatening arrhythmias who had no inducible tachyarrhythmia and 40% without classical criteria for malignant form.

Incidence and prognostic significance of spontaneous and inducible antidromic tachycardia.

AIMS: Orthodromic atrioventricular reentrant tachycardia (ORT) is the most common arrhythmia at electrophysiological study (EPS) in patients with pre-excitation. The purpose of the study was to determine the clinical significance and the electrophysiological characteristics of patients with inducible antidromic tachycardia (ADT). METHODS AND RESULTS: Electrophysiological study was performed in 807 patients with a pre-excitation syndrome in control state and after isoproterenol. Antidromic tachycardia was induced in 63 patients (8%). Clinical and electrophysiological data were compared with those of 744 patients without ADT. Patients with and without ADT were similar in term of age (33 ± 18 vs. 34 ± 17), male gender (68 vs. 61%), clinical presentation with spontaneous atrioventricular reentrant tachycardia (AVRT) (35 vs. 42%), atrial fibrillation (AF) (3 vs. 3%), syncope (16 vs. 12%). In patients with induced ADT, asymptomatic patients were less frequent (24 vs. 37%; <0.04), spontaneous ADT and spontaneous malignant form more frequent (8 vs. 0.5%; <0.001) (16 vs. 6%; <0.002). Left lateral accessory pathway (AP) location was more frequent (51 vs. 36%; P < 0.022), septal location less frequent (40 vs. 56%; P < 0.01). And 1/1 conduction through AP was more rapid. Orthodromic AVRT induction was as frequent (55.5 vs. 55%), but AF induction (41 vs. 24%; P < 0.002) and electrophysiological malignant form were more frequent (22 vs. 12%; P < 0.02). The follow-up was similar; four deaths and three spontaneous malignant forms occurred in patients without ADT. When population was divided based on age (<20/≥20 years), the older group was less likely to have criteria for malignant form. CONCLUSION: Antidromic tachycardia induction is rare in pre-excitation syndrome and generally is associated with spontaneous or electrophysiological malignant form, but clinical outcome does not differ.

B-type natriuretic peptide is an independent predictor of endothelial function in man.

BNP (B-type natriuretic peptide) has been reported to be elevated in preclinical states of vascular damage. To elucidate the relationship between plasma BNP and endothelial function, we have investigated the relationship between BNP and endothelial function in a cohort of subjects comprising healthy subjects as well as at-risk subjects with cardiovascular risk factors. To also clarify the relative contribution of different biological pathways to the individual variation in endothelial function, we have examined the relationship between a panel of multiple biomarkers and endothelial function. A total of 70 subjects were studied (mean age, 58.1±4.6 years; 27% had a history of hypertension and 18% had a history of hypercholesterolaemia). Endothelium-dependent vasodilatation was evaluated by the invasive ACH (acetylcholine)-induced forearm vasodilatation technique. A panel of biomarkers of biological pathways was measured: BNP, haemostatic factors PAI-1 (plasminogen-activator inhibitor 1) and tPA (tissue plasminogen activator), inflammatory markers, including cytokines [hs-CRP (high sensitive C-reactive protein), IL (interleukin)-6, IL-8, IL-18, TNFα (tumour necrosis factor α) and MPO (myeloperoxidase] and soluble adhesion molecules [E-selectin and sCD40 (soluble CD40)]. The median BNP level in the study population was 26.9 pg/ml. Multivariate regression analyses show that age, the total cholesterol/HDL (high-density lipoprotein) ratio, glucose and BNP were independent predictors of endothelial function, and BNP remained an independent predictor (P=0.009) in a binary logistic regression analysis using FBF (forearm blood flow) as a dichotomous variable based on the median value. None of the other plasma biomarkers was independently related to ACH-mediated vasodilatation. In a strategy using several biomarkers to relate to endothelial function, plasma BNP was found to be an independent predictor of endothelial function as assessed by endothelium-dependent vasodilatation in response to ACH.

The impact of renin-angiotensin-aldosterone system blockade on heart failure outcomes and mortality in patients identified to have aortic regurgitation: a large population cohort study.

OBJECTIVES: The aim of this study was to investigate the effect of renin-angiotensin system blockade on outcomes in patients with aortic regurgitation (AR). BACKGROUND: Angiotensin-converting enzyme (ACE) inhibitors have the potential to reduce afterload, blunt left ventricular wall stress, and limit left ventricular dilation and hypertrophy. However, long-term studies have yielded inconsistent results, and very few have assessed clinical outcomes. METHODS: The Health Informatics Centre dispensed prescription and morbidity and mortality database for the population of Tayside, Scotland, was linked through a unique patient identifier to the Tayside echocardiography database. Patients diagnosed with at least moderate AR from 1993 to 2008 were identified. Cox regression analysis was used to assess differences in all-cause mortality and cardiovascular (CV) and AR events (heart failure hospitalizations, heart failure deaths, or aortic valve replacement) between those treated with and without ACE inhibitors or angiotensin receptor blockers (ARBs). RESULTS: A total of 2,266 subjects with AR (median age 74 years; interquartile range: 64 to 81 years) were studied, with a mean follow-up period of 4.4 ± 3.7 years. Seven hundred and five patients (31%) received ACE inhibitor or ARB therapy. There were 582 all-cause deaths (25.7%). Patients treated with ACE inhibitors or ARBs had significantly lower all-cause mortality and fewer CV and AR events, with adjusted hazard ratios of 0.56 (95% confidence interval [CI]: 0.64 to 0.89; p < 0.01) for all-cause mortality, 0.77 (95% CI: 0.67 to 0.89; p < 0.01) for CV events, and 0.68 (95% CI: 0.54 to 0.87; p < 0.01) for AR events. CONCLUSIONS: This large retrospective study shows that the prescription of ACE inhibitors or ARBs in patients with moderate to severe AR was associated with significantly reduced all-cause mortality and CV and AR events. These data need to be confirmed by a prospective randomized controlled outcome trial.

Impact of renin-angiotensin system blockade therapy on outcome in aortic stenosis.

OBJECTIVES: The purpose of this study was to investigate the impact of renin-angiotensin system blockade therapy on outcomes in aortic stenosis (AS). BACKGROUND: Angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) are perceived to be relatively contraindicated in AS. However, inhibitors of the renin-angiotensin system may be beneficial in AS through their cardioprotective and beneficial effects on left ventricular remodeling. METHODS: The Health Informatics dispensed prescribing, morbidity, and mortality database for the population of Tayside, Scotland, was linked through a unique patient identifier to the Tayside echocardiography database (>110,000 scans). Patients with a diagnosis of AS from 1993 to 2008 were identified. Cox regression model (adjusted for confounding variables) and propensity score analysis were used to assess the impact of ACEIs or ARBs on all-cause mortality and cardiovascular (CV) events (CV death or hospitalizations). RESULTS: A total of 2,117 patients with AS (mean age 73 ± 12 years, 46% men) were identified and 699 (33%) were on ACEI or ARB therapy. Over a mean follow-up of 4.2 years, there were 1,087 (51%) all-cause deaths and 1,018 (48%) CV events. Those treated with ACEIs or ARBs had a significantly lower all-cause mortality with an adjusted hazard ratio of 0.76 (95% confidence interval: 0.62 to 0.92, p < 0.0001) and fewer CV events with an adjusted hazard ratio of 0.77 (95% confidence interval: 0.65 to 0.92, p < 0.0001). The outcome benefits of ACEIs/ARBs were further supported by propensity score analysis. CONCLUSIONS: This large observational study suggests that ACEI/ARB therapy is associated with an improved survival and a lower risk of CV events in patients with AS.

Right ventricular pacing impairs endothelial function in man.

AIMS: Clinical trial data show that right ventricular pacing worsens cardiovascular outcomes. The underlying pathophysiology of this is undetermined. We studied the effects of right ventricular pacing on cardiac measures of vascular health (endothelial function), ventricular wall stress (B-type natriuretic peptide), and cardiac reserve (cardiac output response to exercise) in subjects with pacemakers. METHODS AND RESULTS: Twenty-two subjects [mean age 68.4 ± 8.8 (SD) years] with dual-chamber pacemakers implanted for sino-atrial disease were studied in a randomized crossover study comparing minimal right ventricular pacing [RVP-min; pacing with long atrioventricular delay (AVD)] to maximal right ventricular pacing (RVP-max; pacing with short AVD). Endothelial function was measured with reactive hyperaemia peripheral arterial tonometry. Cardiac output at rest and during exercise was determined using an inert gas rebreathing method. Right ventricular pacing was significantly higher in RVP-max when compared with RVP-min (90 ± 16 vs. 15 ± 20%, P < 0.001). Reactive hyperaemia peripheral arterial tonometry index was significantly lower after RVP-max vs. RVP-min (1.73 ± 0.33 vs. 1.96 ± 0.37, P < 0.05). B-type natriuretic peptide was not significantly different between pacing modes (113 ± 80 vs. 104 ± 108 pg/mL, P = NS). Cardiac output at peak exercise was significantly lower during RVP-max (7.65 ± 3.15 vs. 7.05 ± 2.61 L/min, P < 0.05). CONCLUSION: Right ventricular pacing is associated with worsened endothelial function and cardiac reserve.

A randomized comparison of TR band and radistop hemostatic compression devices after transradial coronary intervention.

BACKGROUND: The transradial route for coronary intervention has proven to be safe, effective, and widely applicable in different clinical situations. Several compressive hemostatic devices have been introduced that have shown to be safe and are effective in achieving hemostasis. METHODS: Seven hundred ninety patients were randomly assigned to receive either TR band or Radistop hemostatic compression devices after transradial coronary procedure. The outcome measures were patient tolerance of the device, local vascular complications, and the time taken to achieve hemostasis. RESULTS: The mean age was 62.88 years, and 74.2% of the patients were men. Patient age, height, weight, wrist circumference, body mass index, male sex, hypertension, diabetes, hypercholesterolemia, and smoking incidences were similar in both groups. There were significantly more patients reporting no discomfort in the TR band group compared to the Radistop group (77% vs. 61%; P = 0.0001). Patients in the Radistop group reported significantly more pain across all categories of severity and three patients in the Radistop group were crossed over to TR band because of severe discomfort. Oozing and ecchymosis were seen in about 16% of the patients. Local small hematoma and large hematoma were seen in 5.4% and 2.2% patients respectively, and similar in both groups. Radial artery occlusion at the time of discharge was seen in 9.2% of the patients though only 6.8% showed persistent occlusion at the time of follow-up. The time taken to achieve hemostasis was significantly longer in the TR Band group (5.32 ± 2.29 vs. 4.83 ± 2.23 hr; P = 0.004). There was significantly higher incidence of radial artery occlusion in patients with smaller wrist circumference, the patients who experienced radial artery spasm during the procedure, and patients with no heparin administration during the procedure. CONCLUSIONS: We have shown in a randomized comparison of Radistop and TR band that both devices are safe and effective as hemostatic compression devices following transradial procedures. However, more patients felt discomfort with the Radistop device and the time taken to achieve hemostasis was longer with TR band. © 2010 Wiley-Liss, Inc.

Impact of length and hydrophilic coating of the introducer sheath on radial artery spasm during transradial coronary intervention: a randomized study.

OBJECTIVES: The aim of this study was to assess the impact of length and hydrophilic coating of the introducer sheath on radial artery spasm, radial artery occlusion, and local vascular complications in patients undergoing transradial coronary procedures. BACKGROUND: Radial artery spasm is common during transradial procedures and the most common cause for procedural failure. METHODS: We randomly assigned, in a factorial design, 790 patients scheduled for a transradial coronary procedure to long (23-cm) or short (13-cm) and hydrophilic-coated or uncoated introducer sheaths. The primary outcome measure was clinical evidence of radial artery spasm, and secondary outcome measures were patient discomfort and local vascular complications. RESULTS: Procedural success was achieved in 96% of the cases, and radial artery spasm accounted for 17 of 33 failed cases. There was significantly less radial artery spasm (19.0% vs. 39.9%, odds ratio [OR]: 2.87; 95% confidence interval [CI]: 2.07 to 3.97, p < 0.001) and patient reported discomfort (15.1% vs. 28.5%, OR: 2.27; 95% CI: 1.59 to 3.23, p < 0.001) in patients receiving a hydrophilic-coated sheath. No difference was observed between long and short sheaths. Radial artery occlusion was observed in 9.5% of the patients and was not influenced by sheath length or coating. A local large hematoma or arterial dissection was seen in 2.6% of the patients with no difference in groups allocated at randomization. Younger age, female sex, diabetes, and lower body mass index were identified as independent predictors of radial artery spasm. CONCLUSIONS: Hydrophilic sheath coating, but not sheath length, reduces the incidence of radial artery spasm during transradial coronary procedures.

The feasibility of percutaneous transradial coronary intervention for saphenous vein graft lesions and comparison with transfemoral route.

BACKGROUND: Transradial PCI is rapidly expanding and is effective in complex lesion subset due to miniaturization of devices and accumulated clinical experience. However, the femoral route still remains the usual vascular route used for SVG PCI in most catheterization laboratories. METHODS: We examined 115 consecutive patients undergoing SVG PCI between January 2003 and December 2005 and compared the radial (51 patients) and femoral (64 patients) approaches. RESULTS: Baseline demographics, lesion location, and clinical indication were similar in both groups. GpIIbIIIa inhibitor usage was high in the radial group (78.4% vs. 53.1%, P < 0.01). Angiographic success was similar in both groups, 96% in the radial group vs. 96.8 in the femoral. Total fluoroscopy time (18.59 +/- 12.23 vs. 20.45 +/- 12.9), total procedure time (52.1 +/- 29.5 vs. 43.90 +/- 23.31 min), and the use of total contrast volume (357.0 +/- 174.0 vs. 346.0 +/- 157.0 ml) were similar in the radial and femoral groups, respectively. In-hospital MACE (radial: 2 MI [4.0%] vs. femoral: 1 death [1.6%] and 7 MI [11.0%], P < 0.01) were similar in both groups. Access site vascular complications (radial: 2 [4.0%] vs. femoral: 10 [11.0%], P < 0.001) were significantly less in the radial group. CONCLUSIONS: The transradial approach for SVG PCI is feasible, safe, and as quick as the femoral approach. Procedural success is high with similar radiation and contrast exposure. In-hospital MI in the femoral group is high because of more-unstable patients. However, there are significantly lower vascular complications despite high use of platelet inhibitors in the radial approach.

A comparison of the transradial and the transfemoral approach in chronic total occlusion percutaneous coronary intervention.

BACKGROUND: Transradial coronary intervention is a safe and effective method of percutaneous revascularization. Furthermore, the indications for transradial percutaneous coronary intervention (PCI) are expanding. However, there is limited data on the efficacy and the safety of the transradial approach for chronic total occlusion (CTO) PCI. METHODS: We examined 468 patients who underwent CTO PCI between January 2003 and December 2005, and compared the radial (318 patients) and the femoral (150 patients) approach. RESULTS: Baseline demographics, lesion location, and the vessel treated were similar in both groups. Angiographic success was 82% in radial versus 86% in femoral group, P = 0.28, similar in both groups. Total fluoroscopy time (24.49 +/- 13.18 vs. 24.07 +/- 14.12 min, P = 0.36), total procedure time (54.22 +/- 25.35 vs. 60.23 +/- 28.15 min, P = 0.23), and the use of total contrast volume (395.54 +/- 180.25 vs. 406.15 +/- 173.98 ml, P = 0.27) were similar in radial and femoral group, respectively. In hospital MACE [radial: 12 MI (3.8%) vs. femoral: 1 death (0.7%) and 5 MI (3.5%), P = 0.26] were similar in both groups. Access site vascular complications [radial: 11 (3.5%) vs. femoral: 17 (11.3%), P