Long-term follow-up of the first patients to undergo transcatheter alcohol septal ablation.

We describe the 10-year outcome of the first-in-human series of 12 patients with hypertrophic cardiomyopathy treated with alcohol septal ablation. There was no 30-day mortality. Survival free of death, internal cardiac defibrillator discharge for treatment of ventricular fibrillation or tachycardia, severe New York Heart Association (NYHA) class III/IV and/or Canadian Cardiovascular Society class III/IV symptoms and the need for surgical myectomy in this cohort was 91% at 1 year and 73% at 10 years. The reduction in outflow tract gradient was maintained over the 10 years, from a mean preoperative gradient of 70 mm Hg to a median of 3 mm Hg at 126 months of follow-up (p < 0.01). Two patients (16%) underwent a further ablation procedure. Two patients (16%) suffered sudden cardiac death, 91 and 102 months after the procedure. Long-term symptom benefit was experienced by all patients, with a reduction in mean NYHA class from 2.7 +/- 0.6 before the procedure to 1 after the procedure at the last follow-up (p < 0.01). This historic small cohort study demonstrates that septal ablation can provide long-term haemodynamic and symptomatic benefit.

Incidence of atrial fibrillation after percutaneous closure of patent foramen ovale and small atrial septal defects in patients presenting with cryptogenic stroke.

OBJECTIVE: The occurrence of atrial fibrillation after percutaneous closure of a patent foramen ovale for cryptogenic stroke has been reported in a variable percentage of patients. However, its precise incidence and mechanism are presently unclear and remain to be elucidated. DESIGN: Prospective follow-up study. PATIENTS: Ninety-two patients undergoing a percutaneous patent foramen ovale closure procedure (closure group) for cryptogenic stroke were compared with a similar group of 51 patients, who were medically treated. METHODS: A systematic arrhythmia follow-up protocol to assess the incidence of AF was performed including a 7-day event-loop recording at day 1, after 6 and 12 months in patients of the closure group and compared with those of the medically treated group. RESULTS: The incidence of AF was similar in both study groups during a follow-up of 12 months, including 7.6% (95% CI: 3.1-15.0%) in the closure and 7.8% (95% CI: 2.18-18.9%) in the medically treated group (P=1.0). The presence of a large patent foramen ovale was the only significant risk factor for the occurrence of AF as demonstrated by a multivariate Cox regression analysis (95% CI, 1.275-20.018; P=0.021). CONCLUSIONS: Our findings indicate that patients with cryptogenic stroke and patent foramen ovale have a rather high incidence of AF during a follow-up of 12 months. Atrial fibrillation occurred with a similar frequency whether the patent foramen ovale/atrial septal defect was successfully percutaneously closed or was medically managed. The presence of a large patent foramen ovale was the only significant predictor of AF occurrence during follow-up.

The role of the sizing balloon in selection of the patent foramen ovale closure device size.

OBJECTIVES: To find a correlation between the patent foramen ovale (PFO) size measured by the sizing balloon and the appropriate closure device size. METHODS: The PFO of 57 patients was closed using a sizing balloon. A mathematical model was introduced to relate the PFO balloon waist diameter to the closure device size based on the PFO transformation from a slit-like to a circular form during balloon inflation. According to this model, PFOs smaller than 8 mm should be closed with a 25 mm device, PFOs 8 mm to 11 mm with a 35 mm device, and PFOs larger than 11 mm with an Amplatzer septal occluder. In the first group, 36 patients (63.2%) received an appropriately sized device and six patients (10.5%) received an oversized device. In the second group, 15 patients (26.3%) received an undersized device. RESULTS: A comparison of the PFO dimensions in two views showed that the PFO slit was circular when the balloon was inflated. A six-month echocardiography follow-up was obtained in 46 patients (80.7%). Five patients (13.9%) in the group with an appropriately sized device had a discrete residual shunt during Valsalva. In the second group, five patients (33.3%) had a residual shunt (P = 0.06), of which one was considered large. CONCLUSION: The sizing balloon is helpful in selecting the PFO closure device size. Consequently, the incidence of residual shunt and recurrent events may be reduced.

Not all statins interfere with clopidogrel during antiplatelet therapy.

BACKGROUND: Clopidogrel and statins are frequently coadministered in patients with ischemic heart diseases. Recent reports suggested that clopidogrel's effectiveness in inhibiting adenosine diphosphate (ADP)-induced platelets aggregation is attenuated by co-administration of certain statins. The objective of the present study was to define which statin might interfere with the antiaggregation property of clopidogrel. METHODS: We designed a pharmacokinetic study and tested ex vivo platelet function on 21 healthy volunteers who received clopidogrel and all currently commercially available statins: rosuvastatin [10 mg o.d.], simvastatin [20 mg o.d.], fluvastatin [80 mg o.d.], pravastatin [40 mg o.d.], and atorvastatin [20 mg o.d.]. Each statin was administered for 7 days followed by 1 week of wash-out period with clopidogrel treatment alone. Detection of the statins in the plasma was performed on all blood samples, using HPLC analytical method. RESULTS: All individuals, except one, were responders to clopidogrel with inhibition of ex vivo ADP induced platelet aggregation. All statins, except pravastatin, were detectable in the plasma at the end of each treatment period in all patients, and no statin was detectable after any of the wash-out periods. Clopidogrel was significantly less efficient to prevent platelet aggregation when coadministrated with simvastatin or fluvastatin. No difference was observed in clopidogrel efficacy when coadministered with rosuvastatin, pravastatin or atorvastatin. CONCLUSIONS: This is the first study investigating clopidogrel-statin interactions on ex vivo platelet function with all commercially available statins and which were administered to the same individuals. It demonstrates in healthy volunteers that at the doses used in this study, simvastatin and fluvastatin, but not atorvastatin, pravastatin or rosuvastatin interfere with the anti-aggregation effect of clopidogrel.

[The contribution of molecular genetics to clinical cardiology: the example of hypertrophic cardiomyopathy]. / L'apport de la génétique moléculaire en cardiologie clinique: l'exempte de la cardiomyopathie hypertrophique.

Recent advances in molecular genetics have resulted in the identification of pathogenic mutations in a number of genes which cause hypertrophic cardiomyopathy (HCM). In order to integrate this increasing genetic knowledge of HCM into the cardiology clinic, we offer all patients and their families diagnosis and genetic counselling based on these current data. In addition, within the framework of a multidisciplinary project between the Divisions of Medical Genetics, Cardiology and Pediatric Cardiology of the University Hospitals of Geneva, we have developed a resequencing array enabling rapid molecular diagnosis of HCM. Data from this study will enhance our understanding of the aetiology of HCM, and improve our knowledge of genotype-phenotype correlations. This information will enable us to develop new therapeutic and preventive concepts, with the aim of tailoring therapies to the specific genetic variant of each patient and its family.

A stent is not just a stent: Stent construction and design do matter in its clinical performance.

The undisputed superiority of stents over conventional balloon angioplasty has resulted in a plethora of stents in clinical use. Recent data, however, have indicated not all stent models are the same. Nuances in stent design and construction have impacted significantly on the immediate and long-term clinical outcome. Among the stainless steel stents, those with multicellular or tubular designs have proven to be superior to coiled or hybrid stent models, and thin-strut stents perform better than thicker-strut stents. Coating stainless steel stents with gold, carbide, phosphorylcholine or heparin do not appear to confer any additional benefit, compared with bare metal stents. In contrast, randomised trials have demonstrated that drug-eluting stents coated with various anti-proliferative drugs, with or without a carrier polymer, afford unparalleled restenosis rates compared with non-drug-eluting stents. Drug-eluting stents, however, are expensive, and their long-term durability and safety remain undefined. Notwithstanding these unresolved issues, it is likely that the majority of percutaneous coronary interventions will involve the use of drug-eluting stents once a more attractive balance between their cost and clinical effects is reached.

Outcome after treatment of coronary in-stent restenosis; results from a systematic review using meta-analysis techniques.

AIMS: To evaluate the clinical outcome after treatment of coronary in-stent restenosis. METHODS AND RESULTS: For identification of the relevant literature a specific search strategy was conducted and explicit inclusion criteria were defined to avoid selection bias. Based on the selected literature, a systematic review using descriptive statistics and meta-analysis methods regarding the outcome after treatment of coronary in-stent restenosis was performed. The proportion of patients experiencing a major adverse cardiac event (MACE) as defined by death, myocardial infarction, and target lesion revascularization was the main outcome measure. A total of 1304 citations were identified. Among these, 28 studies (six different treatment modalities) including a total of 3012 patients met the inclusion criteria and were incorporated into this analysis. The estimated average probability of experiencing a major cardiac adverse event after treatment for in-stent restenosis with a follow-up period of 9+/-4 months was 30.0% (25.0-34.9%, 95% confidence interval) with strong evidence for heterogeneity between study specific results (P=0.0001). The clinical outcome was not significantly different between treatment modalities. After adjustment for confounding factors (i.e. lesion length), however, patients undergoing intracoronary radiation showed an estimated advantage of 16.9% (-37.7+/-4.0%, 95% confidence interval) in MACE free survival, as compared to balloon angioplasty. The post-interventional diameter stenosis was the only independent predictor for the long-term outcome after treatment of in-stent restenosis. CONCLUSIONS: Treatment of in-stent restenosis is associated with an overall 30% rate of major adverse cardiac events. Currently, repeat angioplasty is the treatment option of choice, especially when a sufficient acute procedural result can be achieved. Intracoronary radiation should be considered in cases with therapy refractory forms of diffuse in-stent restenosis.

Systemic platelet effects of contrast media: implications for cardiologic research and clinical practice.

BACKGROUND: Angiographic contrast media cause platelet activation and decrease aggregability in vitro. We have previously shown in vitro a significant antiplatelet effect of contrast media at the concentrations obtained locally in the coronary artery during angioplasty. It is not known, however, whether a systemic effect is present. METHOD: Thirty patients undergoing diagnostic coronary angiography were prospectively randomized to receive the nonionic medium iohexol, ionic low-molecular-weight medium ioxaglate, or ionic high-molecular-weight medium diatrizoate. Platelet aggregability was measured before and after the investigation with whole blood electrical impedance aggregometry (WBEA) with collagen agonist and the PFA-100 (Dade, Miami, Fla) platelet function analyzer with combined shear, collagen, and adenosine diphosphate as agonists. RESULTS: With WBEA, with iohexol no difference in impedance change was seen: (medians and ranges) before, 9.8 Omega (4.8-19.2 Omega) versus after, 9.6 Omega (2-19.2 Omega) (P not significant [NS]). With ioxaglate a significant fall was seen: before, 8.6 Omega (6.4-15.2 Omega) versus after, 6.6 Omega (0-12.4 Omega) (P =.004). With diatrizoate a significant and greater fall was seen: before, 10.8 Omega (6.4-17.6 Omega) versus after, 6.6 Omega (0-10.8 Omega) (P =.002). With PFA, no difference in closure time was seen with any medium: iohexol before, 99 seconds (79-142 seconds) versus after, 142 seconds (63-128 seconds) (P NS); ioxaglate before, 120 seconds (75-258 seconds) versus after, 95 seconds (74-258 seconds) (P NS); and diatrizoate before, 114.5 seconds (65-250 seconds) versus after, 100.5 seconds (72-300 seconds) (P NS). CONCLUSIONS: Ionic but not nonionic contrast media have a systemic antiplatelet effect at diagnostic angiographic doses when measured with WBEA. Such an effect has not been shown before. This may explain the observed improved clinical outcome with ionic contrast media but also might confound platelet studies in coronary angioplasty.

Continued benefit of coronary stenting versus balloon angioplasty: five-year clinical follow-up of Benestent-I trial.

OBJECTIVES: This study sought to establish whether the early favorable results in the Benestent-I randomized trial comparing elective Palmaz-Schatz stent implantation with balloon angioplasty in 516 patients with stable angina pectoris are maintained at 5 years. BACKGROUND: The size of the required sample was based on a 40% reduction in clinical events in the stent group. Seven months and one-year follow-up in this trial showed a decreased incidence of restenosis and clinical events in patients randomized to stent implantation. METHODS: Data at five years were collected by outpatient visit, via telephone and via the referring cardiologist. Three patients in the stent group and one in the percutaneous transluminal coronary angioplasty (PTCA) group were lost to follow-up at five years. Major clinical events, anginal status and use of cardiac medication were recorded according to the intention to treat principle. RESULTS: No significant differences were found in anginal status and use of cardiac medication between the two groups. In the PTCA group, 27.3% of patients underwent target lesion revascularization (TLR) versus 17.2% of patients in the stent group (p = 0.008). No significant differences in mortality (5.9% vs. 3.1%), cerebrovascular accident (0.8% vs. 1.2%), myocardial infarction (9.4% vs. 6.3%) or coronary bypass surgery (11.7% vs. 9.8%) were found between the stent and PTCA groups, respectively. At five years, the event-free survival rate (59.8% vs. 65.6%; p = 0.20) between the stent and PTCA groups no longer achieved statistical significance. CONCLUSIONS: The original 10% absolute difference in TLR in favor of the stent group has remained unchanged at five years, emphasizing the long-term stability of the stented target site.

[Statins do not prevent restenosis after coronary angioplasty: where to go from here?]. / Statine verringern nicht die Restenoserate nach konventioneller Koronarangioplastie. Wie geht es jetzt weiter?

BACKGROUND: Despite the use of intracoronary stents, approximately 15-20% of patients who undergo percutaneous transluminal coronary angioplasty (PTCA) experience symptomatic restenosis. Known mechanisms of restenotic lesion formation are smooth muscle cell proliferation, extracellular matrix production, remodeling and decreased programmed cell death (apoptosis). RESULTS AND STUDIES: Experimental observations suggest that HMG-CoA reductase inhibitors ("statins") reduce the risk of restenosis. The activity of statins limits the rate of synthesis, not only of cholesterol, but also of a range of other molecules involved in cellular function. Their benefits in primary and secondary prevention of atherosclerosis have been widely recognized. Clinical trials using different types of statins were designed to evaluate their ability to influence the incidence of restenosis after successful conventional PTCA. The results clearly demonstrated that statins reduce lipid levels but do not prevent restenosis. Experimental evidence has failed to translate into clinical effect. The underlying pathological reasons for this shortcoming as well as promising alternative approaches including vascular gene therapy and brachytherapy will be discussed in this review.

Difference in the mortality of the CABRI diabetic and nondiabetic populations and its relation to coronary artery disease and the revascularization mode.

In diabetics with coronary artery disease (CAD), there remains uncertainty as to whether revascularization by percutaneous transluminal coronary angioplasty (PTCA) or coronary artery bypass surgery (CABG) is preferable. To address this, 4-year mortality and level of pre- and postrevascularization angiographic CAD (measured by a series of coronary scores) were compared between both diabetics and nondiabetics and between revascularization modes in the Coronary Angioplasty versus Bypass Revascularization Investigation population as a whole, and then substratified by diabetic status and then by procedure to which they were randomized. The 1,054 randomized subjects contained 125 diabetics (11.9%) who had significantly greater mortality than nondiabetics (RR 2.19, p = 0.001). Among diabetics or nondiabetics, there was no significant mortality difference between those randomized to PTCA versus those to CABG. Diabetics randomized to PTCA and those to CABG had higher mortalities than respective nondiabetics; the association reached significance only in the former (RR 2.41, p = 0.002). All subgroups had similar prerevascularization CAD. Postrevascularization residual CAD was consistently significantly greater in PTCA than in respective CABG subgroups. Most measurements of CAD were greater in diabetic than in nondiabetic subgroups, but none was significant. In the Coronary Angioplasty versus Bypass Revascularization Investigation, diabetics had double the mortality of nondiabetics; this difference was statistically significant both for the entire population and for those randomized to PTCA, but not for those randomized to CABG. Among diabetics or nondiabetics, there was no significant mortality difference between PTCA and CABG. The higher diabetic mortality was more likely related to more rapid disease progression than to greater postrevascularization disease.

The effect of adjusting for baseline risk factors and post revascularisation coronary disease on comparisons between coronary angioplasty and bypass surgery.

BACKGROUND: In CABRI at 1 year PTCA was associated with greater repeat revascularisation and angina (but not myocardial infarction or death). We determined whether adjusting for baseline risk factors and post revascularisation coronary disease offsets this disadvantage of PTCA. METHODS: In the CABRI population the crude association of revascularisation mode (i.e. PTCA or CABG) with four clinical outcome (i.e. mortality, myocardial infarction, repeat revascularisation and angina) was adjusted for the baseline risk factors using a logistic regression model for each clinical outcome. A number of measures of angiographic coronary disease were used to assess post revascularisation coronary disease. One at a time, each of these measures was added to each of the four outcome models, to adjust for post revascularisation coronary disease. RESULTS: Comparing adjusted and crude unadjusted association of PTCA with repeat revascularisation there was an increase from 12.8 (P<0.0005) (crude relative risk) to 16.7 (P<0.0005) (adjusted odds ratio), with angina, from 1.89 (P=0.001) to 1.98 (P<0.0019), and with mortality from 1.84 (P=0.092) to 2.15 (P=0.060). PTCA was not significantly associated with myocardial infarction, either crudely or after adjustment. CONCLUSION: Adjusting for baseline risk factors and post revascularisation coronary disease tended to strengthen rather than weaken associations between PTCA and 1 year mortality, repeat revascularisation and angina at 1 year.

Early and mid-term angiographic and clinical results after intracoronary duet stent placement.

The Duet stent (Guidant/Advanced Cardiovascular Systems) is a new stent with a corrugated ring design and very limited data on its short- and mid-term performance. Accordingly, in this study we sought to determine the early and mid-term clinical and angiographic outcomes in a moderate-sized series of 86 consecutive patients who underwent placement of 108 premounted Duet stents in 98 coronary lesions. Procedural success, accomplished in all patients, was accompanied by a significant reduction in lesion severity from 89% +/- 11% before to 5% +/- 3% diameter stenosis after the procedure (P = 0.0001) and a 0.9% incidence of subacute stent thrombosis. Angiographic restudy at 5.7 months in 89% of eligible patients revealed a binary in-stent restenosis rate of 26%. Coronary stenting with the new Duet stent confers a low risk of stent thrombosis and a favorable mid-term clinical and angiographic outcome despite the presence of a large proportion of patients at high risk of in-stent restenosis.

Femoral haemostasis after transcatheter therapeutic intervention: a prospective randomised study of the angio-seal device vs. the femostop device.

BACKGROUND: A number of haemostatic devices are available to facilitate early haemostasis following transfemoral interventional procedures. METHODS AND RESULTS: We have prospectively compared 150 patients (age: 57+/-12 years, mean+/-S.D.) who were randomly assigned to either external compression using the FemoStop device or direct closure of the arterial puncture using the Angio-Seal device. The Angio-Seal was deployed in the catheter laboratory after the conclusion of the procedure. Patients, randomised to FemoStop, had their sheath removed when the activated clotting time (ACT) was less than 100 s before applying the device. The primary endpoint was the composite of bleeding, haematoma formation, bruise, requirement for blood transfusion, clinical indication for ultrasound examination at 2 h and 24 h following the procedure and crossover to either method at 2 and 24 h after the device deployment. The 95% of the Angio-Seal and 96% of FemoStop patients were discharged on the day following the procedure. An increased number of patients in the Angio-Seal group reached a clinical end-point within the first 2 h (45% vs. 3%, P<0.0001). This difference became insignificant at 24 h (25% vs. 30%, P=0.6). CONCLUSION: Although less comfortable, the overall efficacy of the FemoStop appeared to be higher than that of the Angio-Seal device.

Relation between coronary artery disease, baseline clinical variables, revascularization mode, and mortality. CABRI Participants. Coronary Angioplasty vs. Bypass Revascularisation Investigation.

The Coronary Angioplasty vs. Bypass Revascularisation Investigation (CABRI) trial comparing percutaneous transluminal coronary angioplasty (PTCA) with coronary artery bypass grafting did not show a difference in mortality with either procedure. Nonrandomized studies suggest that coronary artery disease (CAD) severity and distribution influences outcome. In the present study we explored the effect of prerevascularization CAD on 1-year mortality in the CABRI population, while adjusting for other baseline variables. Of the 1,054 patients recruited, there were sufficient angiographic results to derive the CAD scores in 974 (92.4%). Of these 974, there were 32 deaths. A number of CAD scores, both weighted for proximal disease (Duke and Leaman) and nonweighted, were used. These scores were then cross-tabulated against mortality. Demographic and clinical variables were also cross-tabulated against mortality and used to derive an initial logistic regression model to predict mortality. The effect of adding each of the CAD scores to this initial model was then assessed. After inclusion of the CAD scores, the best model was: (1) presence of peripheral vascular disease (odds ratio [OR] 3.89, p = 0.0025), (2) previous cerebrovascular accident (OR 2.86, p = 0.043), (3) older age (OR 1.05, p = 0.039), (4) a higher Duke score (OR 2.84, p = 0.0061), and (5) having undergone PTCA (OR 2.12, p = 0.047). In the CABRI population, adjustment for baseline variables, including prerevascularization CAD, revealed significantly higher mortality in those who underwent PTCA than in those who underwent coronary artery bypass grafting.