QTc interval evaluation in patients with right bundle branch block or bifascicular blocks.

BACKGROUND: The right bundle branch block (RBBB) and the bifascicular blocks affect QRS duration in the right precordial leads, which are usually used for QT interval determination. Up to now, there is no clear recommendation how to determine QT interval in patients with RBBB or bifascicular block. HYPOTHESIS: The hypothesis of the present study was to evaluate the feasibility of a simple formula for RBBB and bifascicular block correction, thereby making it easier to determine the QTc interval. METHODS: In patients with intrinsic QRS duration <120 ms, artificial RBBB with either left posterior (LPFB) or left anterior fascicular block (LAFB), created by left ventricular pacing maneuvers, were corrected using the Bogossian formula (QTm) and afterward were heart rate corrected (QTmc). Heart rate correction was performed using different heart rate formulas in comparison to each other. The QTmc intervals were compared in each patient with the QTc interval during intrinsic rhythm. RESULTS: A total of scheduled 71 patients were included in this prospective multicenter observational comparative study. Compared to intrinsic QTc interval, the mean ΔQTmc interval by combination of the Bogossian and the Hodge formulas was -3 ± 24 ms in RBBB + LPFB (P = .44) and -6 ± 25 ms in RBBB + LAFB (P = .15). The Bogossian formula showed a significant deviation from the actual QTc interval with both the Bazett and the Fridericia formulas. CONCLUSION: In combination with the Hodge formula, the Boggosian formula delivered the best results in comparing the true QTc interval in narrow QRS with the QTmc interval in the presence of a bifascicular block.

Elite athletes as research model: vitamin D insufficiency associates with elevated central blood pressure in professional handball athletes.

PURPOSE: Low vitamin D levels have been associated with elevated blood pressure in the general population. Prospective studies, however, have produced conflicting evidence about the blood pressure-lowering effects of vitamin D supplementation. Cardiorespiratory fitness may modulate the vitamin D-blood pressure association. We therefore examined this association in professional athletes, whose high training load serves as a biological control for physical fitness. METHODS: 50 male professional handball players (age 26 ± 5 years) were examined. We assessed the central aortic pressure parameters using transfer function-based analysis of oscillometrically obtained peripheral arterial waveforms. Serum 25-OH vitamin D concentrations were determined by chemiluminescent immunoassay. The threshold for insufficiency was set at values of < 30 ng/mL. RESULTS: Central blood pressure (cBP) was 98 ± 7/60 ± 10 mmHg. The aortic pulse wave velocity (PWV) was 6.3 ± 1.0 m/s. Nine athletes (18%) displayed insufficient 25-OH vitamin D levels and had a significantly (p < 0.01) higher cBP compared with the 41 (82%) athletes with sufficient 25-OH vitamin D levels (106 ± 5/68 ± 8 vs. 97 ± 7/58 ± 9 mmHg). Central systolic blood pressure (cSBP) in vitamin D-sufficient athletes was significantly lower in comparison to the healthy reference population (97 mmHg vs. 103 mmHg, p < 0.001). This significance of difference was lost in vitamin D-insufficient athletes (106 mmHg vs. 103 mmHg, p = 0.12). CONCLUSION: Significantly raised central systolic and diastolic blood pressure in vitamin D-insufficient elite athletes implicates vitamin D as a potential modifier of vascular functional health.

An early analysis of cost-utility of baroreflex activation therapy in advanced chronic heart failure in Germany.

BACKGROUND: This study aimed to evaluate cost-utility of baroreflex activation therapy (BAT) using the Barostim neo™ device (CVRx Inc., Minneapolis, MN, USA) compared with optimized medical management in patients with advanced chronic heart failure (NYHA class III) who were not eligible for treatment with cardiac resynchronization therapy, from a statutory health insurance perspective in Germany over a lifetime horizon. METHODS: A decision analytic model was developed using the combination of a decision tree and the Markov process. The model included transitions between New York Heart Association (NYHA) health states, each of which is associated with a risk of mortality, hospitalization, cost, and quality of life. The effectiveness of BAT was projected through relative risks for mortality (obtained by application of patient-level data to the Meta-analysis Global Group in Chronic Heart Failure risk prediction model) and hospitalization owing to worsening of heart failure (obtained from BAT Randomized Clinical Trial). All patients were in NYHA class III at baseline. RESULTS: BAT led to an incremental cost of €33,185 (95% credible interval [CI] €24,561-38,637) and incremental benefits of 1.78 [95% CI 0.45-2.71] life-years and 1.19 [95% CI 0.30-1.81] quality-adjusted life-years (QALYs). This resulted in an incremental cost-effectiveness ratio of €27,951/QALY (95% CI €21,357-82,970). BAT had a 59% probability of being cost-effective at a willingness-to-pay threshold of €35,000/QALY (but 84% at a threshold of €52,000/QALY). CONCLUSIONS: BAT can be cost-effective in European settings in those not eligible for cardiac resynchronization therapy among patients with advanced heart failure.

Cryoballoon ablation of persistent atrial fibrillation: feasibility and safety of left atrial roof ablation with generation of conduction block in addition to antral pulmonary vein isolation.

AIMS: Although the generation of linear lesions by ablation improves success rates in patients with persistent atrial fibrillation (AF), the procedure has been considered unsuitable for cryoablation balloon catheter technologies. We developed a technique for linear ablations, using second-generation cryoballoon technology. METHODS AND RESULTS: This was a single-arm, prospective study in 76 patients with persistent AF treated consecutively at our centre. Cryoablation was performed using a 28 mm second-generation cryoballoon. The first cryoenergy application was performed in close proximity to the position during isolation of the left superior pulmonary vein (PV). Sequential overlapping freezes were applied along the left atrial (LA) roof by slight clockwise rotation of the sheath in combination with slight retraction of the sheath and incremental advancement of the cryoballoon, until reaching the original position for right superior PV isolation. The acute endpoint was the creation of a roofline, defined as complete conduction block across the LA roof >120 ms and ascending activation across the posterior LA wall. Acute success in roofline generation was achieved in 88% of patients, applying on average five (median 4-6) freezes with nadir temperature of -40°C (-36 to -44°C). In five patients, conduction block could not be achieved. No phrenic nerve injuries occurred during roofline generation. CONCLUSION: Generation of linear roofline lesions is possible with the second-generation cryoballoon. The technique can be used in combination with PV isolation to treat persistent AF with good acute success rates, short procedure times, and acceptable safety concerns. If validated by further studies, the method would be an appealing alternative to radiofrequency ablation techniques.

Barostim Implantation with Ipsilateral Carotid Endarterectomy as a One-Stage Procedure.

Clinical trials have demonstrated significant and lasting reductions in arterial pressure from baroreflex activation therapy (BAT), resulting from electrical stimulation of the carotid sinus in patients with resistant arterial hypertension. Significant carotid atherosclerosis, however, has been a contraindication for ipsilateral implantation due to a potentially increased risk of periprocedural stroke and uncertain antihypertensive efficacy. Here, we describe the first case in which BAT was applied safely and effectively in a patient with distinct cerebral arteriosclerosis after ipsilateral carotid endarterectomy as a one-stage procedure without neurologic complications. BAT resulted in satisfactory blood pressure levels despite distinct cerebral atherosclerosis after an 18-month follow-up period.

Rescue baroreflex activation therapy after Stanford B aortic dissection due to therapy-refractory hypertension.

Clinical trials have demonstrated significant and durable reduction in arterial pressure from baroreflex activation therapy (BAT) in patients with resistant arterial hypertension. There is a lack of data, however, concerning the use of BAT in a rescue approach during therapy-refractory hypertensive crisis resulting in life-threatening end-organ damage. Here, we describe the first case in which BAT was applied as a rescue procedure in an intensive care setting after ineffective maximum medical treatment. A 34-year-old male patient presented with Stanford B aortic dissection and hypertensive crisis. The dissection membrane extended from the left subclavian artery down to the right common iliac artery, resulting in a total arterial occlusion of the right leg. After emergency thoracic endovascular aortic repair and femorofemoral crossover bypass, the patient developed a compartment syndrome of the right lower limb, ultimately leading to amputation of the right leg above the knee. Even under deep sedation recurrent hypertensive crises of up to 220 mm Hg occurred that could not be controlled by eight antihypertensive drugs of different classes. Screening for secondary hypertension was negative. Eventually, rescue implantation of right-sided BAT was performed as a bailout procedure, followed by immediate activation of the device. After a hospital stay of a total of 8 weeks, the patient was discharged 2 weeks after BAT initiation with satisfactory blood pressure levels. After 1-year follow-up, the patient has not had a hypertensive crisis since the onset of BAT and is currently on fourfold oral antihypertensive therapy. The previously described bailout procedures for the treatment of life-threatening hypertensive conditions that are refractory to drug treatment have mainly comprised the interventional denervation of renal arteries. The utilization of BAT is new in this emergency context and showed a significant, immediate, and sustained reduction of blood pressure levels after activation. To our knowledge, we report the first case of an immediate activation of a barostim while the device is usually not activated before 2 to 4 weeks after implantation to allow time for the surgical site to heal. During the follow-up period, the healing process was not impaired, and a significant, immediate, and sustained reduction of blood pressure levels after activation could be observed. This treatment option offers maximum adherence to antihypertensive therapy to avoid future cardiovascular end-organ damage and possibly reduce antihypertensive medication and undesirable side effects.

Electrophysiological studies in patients with pulmonary hypertension: a retrospective investigation.

Few studies have investigated patients with pulmonary hypertension and arrhythmias. Data on electrophysiological studies in these patients are rare. In a retrospective dual-centre design, we analysed data from patients with indications for electrophysiological study. Fifty-five patients with pulmonary hypertension were included (Dana Point Classification: group 1: 14, group 2: 23, group 3: 4, group 4: 8, group 5: 2, and 4 patients with exercised-induced pulmonary hypertension). Clinical data, 6-minute walk distance, laboratory values, and echocardiography were collected/performed. Nonsustained ventricular tachycardia was the most frequent indication (n = 15) for an electrophysiological study, followed by atrial flutter (n = 14). In summary 36 ablations were performed and 25 of them were successful (atrial flutter 12 of 14 and atrioventricular nodal reentrant tachycardia 4 of 4). Fluoroscopy time was 16 ± 14.4 minutes. Electrophysiological studies in patients with pulmonary hypertension are feasible and safe. Ablation procedures are as effective in these patients as in non-PAH patients with atrial flutter and atrioventricular nodal reentrant tachycardia and should be performed likewise. The prognostic relevance of ventricular stimulations and inducible ventricular tachycardias in these patients is still unclear and requires further investigation.

Risk of bleeding after prehospital administration of high dose tirofiban for ST elevation myocardial infarction.

BACKGROUND: In most patients with ST-elevation myocardial infarction (STEMI), antiplatelet drugs are already administrated in the ambulance, before hospital admission. We investigated the safety of prehospital initiation of a high dose of the glycoprotein IIb/IIIa inhibitor tirofiban on top of aspirin, clopidogrel and heparin. METHODS: It concerns a sub-analysis of the On-TIME 2 trial. 1398 patients were enrolled and 1275 patients (91.2%) had clinical follow up. Non CABG-related bleeding was defined according to the TIMI criteria. Logistic regression was used to determine predictors of 30-day bleeding. The independent association between bleeding and mortality (30-day and 1-year) was evaluated using Cox proportional Hazard models. RESULTS: Bleeding (major or minor) was observed in 47 patients (3.7%), with only 13 patients (1%) with major bleeding. The strongest independent determinants of bleeding were age (OR 1.05, 95% CI 1.01-1.08, p=0.011), Killip class >1 at admission (OR 2.5, 95% CI 1.2-5.3, p=0.020) and intra aortic balloon pump (IABP) use (OR 4.2, 95% CI 1.6-11.1, p=0.003). High dose tirofiban was not an independent predictor of bleeding (OR 1.7, 95% CI 0.9-3.2, p=0.116). Bleeding was associated with an increased risk of 30-day mortality (HR 5.5, 95% CI 1.6-7.8, p<0.001) and one-year mortality (HR 3.2, 95% CI 1.4-7.2, p=0.005). CONCLUSION: Prehospital use of high dose tirofiban is safe and associated with a low risk of bleeding. Age, Killip class >1, IABP use, but not high dose tirofiban are independent determinants of bleeding in STEMI patients. Bleeding is independently associated with 30-day and 1-year mortality.

Higher efficacy of pre-hospital tirofiban with longer pre-treatment time to primary PCI: protection for the negative impact of time delay.

AIMS: To evaluate the impact of longer duration of pre-hospital initiated antiplatelet and antithrombotic therapy on outcome in patients with ST-segment elevation myocardial infarction (STEMI). METHODS AND RESULTS: In this sub-analysis of the Ongoing Tirofiban in Myocardial Evaluation (On-TIME) 2 trial, we studied, in 1,370 patients, the effect of pre-treatment time (time from administering study medication to time of angiography) on complete ST-segment resolution (STR), initial patency and 30-day mortality. Study medication consisted of high dose tirofiban (HDT) or control (placebo or no HDT) on top of high dose clopidogrel, aspirin and unfractionated heparin. Median pre-treatment time was 55 min (44-70). Longer pre-treatment was associated with longer transportation times, longer in-hospital delay, longer total ischaemic time (all p<0.001) and higher 30-day mortality (3.6% vs. 1.8%, p=0.046). Longer HDT pre-treatment time was independently associated with increased complete STR both before (odds ratio [OR] 1.51, 95%; confidence interval [CI] 0.98-2.32; p=0.06) and after PCI (OR 1.43, 95%; CI 1.02-2.02; p=0.039) and with a significantly improved initial TIMI 2 or 3 flow (51.4% vs. 43.4%, p=0.042) and reduced 30-day mortality (2.1% vs. 5.0%, p=0.047) as compared to longer control pre-treatment. CONCLUSIONS: Longer time delay before primary PCI is associated with increased mortality. Pre-treatment with high dose tirofiban, however, may compensate for this negative effect by improving ST-segment resolution and initial patency and by reducing mortality. Further studies should be performed to confirm that this is an attractive therapy for patients with longer delays to reperfusion.

Facilitated reperfusion with prehospital glycoprotein IIb/IIIa inhibition: predictors of complete ST-segment resolution before primary percutaneous coronary intervention in the On-TIME 2 trial: correlates of reperfusion before primary PCI.

OBJECTIVE: The objective of this study is to evaluate the incidence, predictors, and outcome of complete ST-segment resolution (STR) during transportation after pretreatment with dual or triple antiplatelet therapy in the Ongoing Tirofiban in Myocardial Infarction Evaluation (On-TIME) 2 trial. METHODS: Patients with ST-segment elevation myocardial infarction were randomized in the ambulance to pretreatment with high-dose tirofiban (HDT) or to a control pretreatment (placebo or no HDT) on top of 600-mg clopidogrel, 500-mg aspirin, and 5000-IU unfractionated heparin. Complete STR was defined as ≥70% STR on the electrocardiogram obtained before percutaneous coronary intervention (PCI) as compared with the inclusion electrocardiogram. RESULTS: Complete STR before PCI occurred in 16.8% (n = 188/1121) and more frequently in the HDT group (19.0% vs 14.6%, P = .05). Independent predictors for complete STR before PCI were younger age (odds ratio [OR], 0.82; 95% confidence interval [CI], 0.70-0.96, P = .01 per 10 year increase), fast diagnosis (OR, 0.97; 95% CI, 0.97-1.0, P = .004 per 15-minute increase time from symptom onset to diagnosis), longer pretreatment time (OR, 1.09; 95% CI, 1.03-1.16, P = .003 per 15-minute increase time start study medication to angiography), and randomization to HDT (OR, 1.39; 95% CI, 1.0-1.9, P = .05). Complete STR before PCI was associated with very low 30-day (0.5% vs 2.8%, P = .07) and 1-year (1.1% vs 5.0%, P = .019) mortality. CONCLUSIONS: Dual or triple antiplatelet pretreatment in the ambulance results in complete STR before PCI in 17% of patients. Fast ST-segment elevation myocardial infarction diagnosis, prehospital initiation of pretreatment early after symptom onset, and HDT independently predicted STR before PCI. Complete STR is associated with improved clinical outcome.

Pre-hospital administration of tirofiban in diabetic patients with ST-elevation myocardial infarction undergoing primary angioplasty: a sub-analysis of the On-Time 2 trial.

AIMS: Glycoprotein IIb/IIIa blocking agents seem to improve percutaneous coronary intervention (PCI) results in patients with ST-elevation myocardial infarction (STEMI). We aimed to compare the effect of pre-hospital administration of tirofiban in STEMI patients with and without diabetes mellitus (DM) treated with primary PCI. METHODS AND RESULTS: We performed a pre-specified sub-analysis of the randomised On-Time II trial (n=984) and it's open label run-in phase (n=414), which investigated pre-hospital administration of high dose tirofiban in STEMI patients treated with primary PCI. Two-hundred and twenty (16%) diabetic patients (known DM or Hba1C ≥6.2%) were included, 101 in the placebo group and 119 in the tirofiban group. In patients with DM, randomisation to tirofiban resulted in a lower residual ST deviation (5.1±8.5 mm vs. 6.2±5.6 mm, p=0.003), a reduced infarct size (CK 1694±1925 U/L vs. CK 2040±1829 U/L, p=0.02) and a trend towards lower one-year mortality (4.6% vs. 11.6%, p=0.07). The beneficial effects of tirofiban were more pronounced in diabetic patients compared to patients without diabetes. CONCLUSIONS: Pre-hospital administration of tirofiban in diabetic STEMI patients treated with primary PCI improves ST resolution and reduces myocardial infarct size. Tirofiban seems particularly beneficial in patients with diabetes.

Prehospital triple antiplatelet therapy in patients with acute ST elevation myocardial infarction leads to better platelet aggregation inhibition and clinical outcome than dual antiplatelet therapy.

OBJECTIVE: To assess whether prehospital initiation of high-dose tirofiban in addition to high-dose clopidogrel results in more adequate inhibition of platelet aggregation (IPA) and better clinical outcome after primary percutaneous coronary intervention (PCI). METHODS: Prespecified two-centre substudy of the prospective, international, multicentre, placebo controlled Ongoing Tirofiban in Myocardial Infarction Evaluation trial 2 (On-TIME-2 trial). 648 of 964 (67%) patients in the On-TIME-2 trial with ST elevation myocardial infarction undergoing primary PCI were studied. Pre-PCI IPA after early prehospital initiation of high-bolus dose (25 µg/kg) tirofiban was compared to placebo in addition to acetylsalicylic acid, unfractionated heparin and 600 mg clopidogrel. RESULTS: IPA was measured at a median of 60 min after study medication administration. In all four tests: Fe induced platelet aggregation, ADP induced platelet aggregation, platelet function analyser (PFA)-100 (collagen-epinephrine and collagen-ADP cartridge) IPA was higher in patients pretreated with high-dose tirofiban (p<0.001 for all tests), even after >74 min of pretreatment. Patients in the highest quartile of IPA had less residual ST segment deviation 1 h post-PCI (p value for trend: p=0.001, 0.004, 0.001, 0.002 respectively). There was a significant relationship between PFA-100 (both cartridges) and major adverse cardiovascular events (MACE, p=0.028, p=0.035) and early thrombosis (p=0.009, p=0.007). CONCLUSIONS: 60 min of prehospital initiated antiplatelet treatment including high-dose tirofiban resulted in higher levels of IPA compared to pretreatment with acetylsalicylic acid and high-dose clopidogrel alone, even after longer pretreatment times. Levels of IPA were significantly related to ST resolution and MACE, including stent thrombosis. This substudy confirms the main findings of the On-TIME2 trial that clopidogrel alone is suboptimal, even at high dose and administered well in advance of primary PCI.

Effect of early, pre-hospital initiation of high bolus dose tirofiban in patients with ST-segment elevation myocardial infarction on short- and long-term clinical outcome.

OBJECTIVES: The purpose of this trial was to study the effect of a high bolus dose (HBD) of tirofiban on clinical outcome in patients undergoing primary percutaneous coronary intervention for ST-segment elevation myocardial infarction (STEMI). BACKGROUND: The On-TIME 2 (Ongoing Tirofiban In Myocardial infarction Evaluation 2) placebo-controlled, double-blind, randomized trial showed that early administration of HBD tirofiban in the ambulance improves ST-segment resolution in patients with STEMI undergoing primary percutaneous coronary intervention. The effect of early tirofiban treatment on clinical outcome is unclear. METHODS: The On-TIME 2 trial consisted of 2 phases: an open-label phase, followed by a double-blind, placebo-controlled phase. STEMI patients were randomized to either HBD tirofiban or no tirofiban (phase 1) or placebo (phase 2) in addition to aspirin, heparin, and high-dose clopidogrel. The protocol pre-specified a pooled analysis of the 2 study phases to assess the incidence of major adverse cardiac events at the 30-day follow-up and on total mortality at the 1-year follow-up. RESULTS: During a 3-year period, 1,398 patients were randomized, 414 in phase 1 and 984 in phase 2. Major adverse cardiac events at 30 days were significantly reduced (5.8% vs. 8.6%, p = 0.043). There was a strong trend toward a decrease in mortality (2.2% vs. 4.1%, p = 0.051) in patients who were randomized to tirofiban pre-treatment, which was maintained during the 1-year follow-up (3.7% vs. 5.8%, p = 0.08). No clinically relevant difference in bleeding was observed. CONCLUSIONS: Early, pre-hospital initiation of HBD tirofiban, in addition to high-dose clopidogrel, improves the clinical outcome after primary percutaneous coronary intervention in patients with STEMI. (Ongoing 2b/3a inhibition In Myocardial infarction Evaluation; ISRCTN06195297).

Tirofiban as adjunctive therapy for acute coronary syndromes and percutaneous coronary intervention: a meta-analysis of randomized trials.

AIMS: To perform a thorough and updated systematic review of randomized clinical trials comparing tirofiban vs. placebo or vs. abciximab. METHODS AND RESULTS: We searched for randomized trials comparing tirofiban vs. placebo or any active control. Odds ratios (OR) were computed from individual studies and pooled with random-effect methods. Thirty-one studies were identified involving 20,006 patients (12 874 comparing tirofiban vs. heparin plus placebo or bivalirudin alone, and 7132 vs. abciximab). When compared with placebo, tirofiban was associated at 30 days with a significant reduction in mortality [OR = 0.68 (0.54-0.86); P = 0.001] and death or myocardial infarction (MI) [OR = 0.69 (0.58-0.81); P < 0.001]. The treatment benefit persisted at follow-up but came at an increased risk of minor bleedings [OR = 1.42 (1.13, 1.79), P = 0.002] or thrombocytopenia. When compared with abciximab, mortality at 30 days did not differ [OR = 0.90 (0.53, 1.54); P = 0.70], but in the overall group tirofiban trended to increase the composite of death or MI [OR = 1.18 (0.96, 1.45); P = 0.11]. No such trend persisted at medium-term follow-up or when appraising studies testing tirofiban at 25 microg/kg bolus regimen. CONCLUSION: Tirofiban administration reduces mortality, the composite of death or MI and increases minor bleedings when compared with placebo. An early ischaemic hazard disfavouring tirofiban was noted when compared with abciximab in studies based on 10 but not 25 microg/kg tirofiban bolus regimen.

Effects of candesartan cilexetil "add-on" treatment in congestive heart failure outpatients in daily practice.

AIMS: In the present study, we investigated the efficacy and safety of candesartan cilexetil (candesartan) as "add-on" treatment in congestive heart failure (CHF) in daily practice. METHODS AND RESULTS: In this open-label, multicenter study 414 CHF outpatients (NYHA II/III) with left ventricular ejection fraction (LVEF) < or = 40% and plasma brain natriuretic peptide (BNP) levels > 200 pg/ml at baseline were enrolled. Patients were treated with standard therapy including at least one angiotensin converting enzyme inhibitor in addition to another CHF drug; 91% of the patients received beta-blockers. Candesartan was uptitrated to 32 mg/day (target dose if tolerated) during 6 weeks followed by constant dosing over 16 weeks. The primary endpoint plasma BNP was significantly reduced by 25% at week 22 (from 394 to 295 pg/ml, P < 0.0001 vs. baseline). Candesartan produced early and sustained improvements of plasma BNP/NT-pro-BNP, LVEF, and quality of life (SF-36) compared to baseline. Of patients on beta-blockers, 37% improved towards NYHA II/I at week 22 (P < 0.0001) and 53.5% of the patients in NYHA III at baseline improved into NYHA II/I at week 22 (n = 232, P < 0.0001). Candesartan was well tolerated; no unexpected findings were reported besides known adverse reactions including hypotension, hyperkalemia, and serum creatinine elevations. CONCLUSION: Candesartan "add-on" treatment provides a good benefit/risk ratio in CHF outpatients in daily practice, although high-risk patients should be managed with frequent monitoring of BP, serum potassium, and renal function.

Prehospital initiation of tirofiban in patients with ST-elevation myocardial infarction undergoing primary angioplasty (On-TIME 2): a multicentre, double-blind, randomised controlled trial.

BACKGROUND: The most effective magnitude and timing of antiplatelet therapy is important in patients with acute ST-elevation myocardial infarction (STEMI). We investigated whether the results of primary coronary angioplasty (PCI) can be improved by the early administration of the glycoprotein IIb/IIIa blocker tirofiban at first medical contact in the ambulance or referral centre. METHODS: We undertook a double-blind, randomised, placebo-controlled trial in 24 centres in the Netherlands, Germany, and Belgium. Between June 29, 2006, and Nov 13, 2007, 984 patients with STEMI who were candidates to undergo PCI were randomly assigned to either high-bolus dose tirofiban (n=491) or placebo (N=493) in addition to aspirin (500 mg), heparin (5000 IU), and clopidogrel (600 mg). Randomisation was by blinded sealed kits with study drug, in blocks of four. The primary endpoint was the extent of residual ST-segment deviation 1 h after PCI. Analysis was by intention to treat. The trial is registered, number ISRCTN06195297. FINDINGS: 936 (95%) patients were randomly assigned to treatment after a prehospital diagnosis of myocardial infarction in the ambulance. Median time from onset of symptoms to diagnosis was 76 min (IQR 35-150). Mean residual ST deviation before PCI (10.9 mm [SD 9.2] vs 12.1 mm [9.4], p=0.028) and 1 h after PCI (3.6 mm [4.6] vs 4.8 mm [6.3], p=0.003) was significantly lower in patients pretreated with high-bolus dose tirofiban than in those assigned to placebo. The rate of major bleeding did not differ significantly between the two groups (19 [4%] vs 14 [3%]; p=0.36). INTERPRETATION: Our finding that routine prehospital initiation of high-bolus dose tirofiban improved ST-segment resolution and clinical outcome after PCI, emphasises that further platelet aggregation inhibition besides high-dose clopidogrel is mandated in patients with STEMI undergoing PCI.

Circumferential pulmonary vein isolation with the cryoballoon technique results from a prospective 3-center study.

OBJECTIVES: The purpose of this study was to investigate the efficacy safety of the novel cryoballoon device (Arctic Front, Cryocath, Quebec, Canada). BACKGROUND: Antral pulmonary vein (PV) ablation with radiofrequency energy is widely used as a strategy for catheter ablation of paroxysmal atrial fibrillation (PAF). A novel double lumen cryoballoon catheter was designed for circumferential pulmonary vein isolation (PVI) with the cryoablation technique. METHODS: We consecutively enrolled 346 patients with symptomatic, drug refractory paroxysmal (n = 293) or persistent (n = 53) atrial fibrillation (AF). In all patients, PVI of all targeted PVs was the therapeutic aim. The primary end points of this nonrandomized study were: 1) acute isolation rate of targeted PV; and 2) first electrocardiogram-documented recurrence of AF. The secondary end point was occurrence of PV stenosis or atrio-esophageal fistula. RESULTS: The 1,360 of 1,403 PVs (97%) were targeted with balloons or balloons in combination with the use of Freezor Max (Cryocath). We found that ablation with the cryoballoon resulted in maintenance of sinus rhythm in 74% of patients with PAF and 42% of patients with persistent AF. No PV narrowing occurred. The most frequent complication was right phrenic nerve palsy observed during cryoballoon ablation at the right superior PV. CONCLUSIONS: Pulmonary vein isolation with a new cryoballoon technique is feasible. Sinus rhythm can be maintained in the majority of patients with PAF by circumferential PVI using a cryoballoon ablation system. Cryoablation was less effective in patients with persistent AF than in patients with PAF.

Acute success and persistence of bidirectional conduction block in the cavotricuspid isthmus one month post cryocatheter ablation of common atrial flutter.

INTRODUCTION: Cryoablation is successful in the treatment of common atrial flutter. Long-term clinical success is mainly dependent on persistence of bidirectional conduction block (BCB) in the inferior cavotricuspid isthmus (CTI). Only few data on persistence of BCB post cryoablation with the reported technique are available. This prospective study aimed to test efficacy of cryo energy and persistence of BCB in the CTI 1 month post cryoablation. METHODS: Cryoablation of the CTI was performed in 50 consecutive patients (64 +/- 12 years, 40 males) with symptomatic common atrial flutter using a novel 9 Fr 8-mm-tip catheter. BCB in the CTI 30 minutes following the final cryoapplication was the ablation endpoint. Thirty days post ablation, persistence of BCB was controlled by repeat electrophysiological study (EPS). RESULTS: In all patients BCB was achieved with a mean of 9 (IQR 7-17.5) cryo applications and a mean cryo time of 2,378 seconds (IQR 1,680-3,474 seconds). In 5 of 50 patients, common atrial flutter recurred within 1 month post cryoablation. In 30 of 32 recurrence-free patients, persistence of BCB was verified. In 2 patients, resumption of isthmus conduction was detectable. Including relapses, 81.1% of patients (30/37) showed persistence of BCB. No patients reported pain during cryoapplication. No procedural complications were observed. CONCLUSIONS: Cryoablation of the CTI using a large-tip catheter is feasible and safe in the treatment of common atrial flutter. Acute and short-term success rates are comparable to those reported for radiofrequency (RF) ablation. Besides short-term clinical success, the persistence of BCB demonstrates efficacy of the cryoablation technique.

The value of magnetic resonance imaging for the diagnosis of arrhythmogenic right ventricular cardiomyopathy.

This study evaluated the diagnostic significance of a magnetic resonance imaging (MRI) based scoring model for identification of arrhythmogenic right ventricular cardiomyopathy (ARVC) in patients with MRI evidence of RV abnormalities. Fifty-three patients with RV myocardial abnormalities on MRI were divided into a group with ARVC 1 (n=17) and a group with other RV arrhythmias (n=37). Decision tree learning (DTL) and linear classification (based on a modified ARVC scoring model of major and minor criteria) were used to identify and assess MRI criterion information value, and to induce ARVC diagnostic rules. All major ARVC criteria were more frequent in the ARVC group. Among minor criteria regional RV hypokinesia, mild segmental RV dilatation, and prominent trabeculae were more frequent in the ARVC group while mild global RV dilatation was more frequent in the non-ARVC group. RV aneurysm achieved highest importance in ARVC diagnosis (predictive accuracy 76.8%). Better diagnostic accuracy (sensitivity 93.3%, specificity 89.5%) was achieved when the MRI score for the major and minor criteria reached threshold value of four: two major criteria, or one major and two minor, or four minor criteria. Combinations between major and minor criteria contributed to a statistically valid model for ARVC diagnosis.

Invasive optimization of cardiac resynchronization therapy: role of sequential biventricular and left ventricular pacing.

BACKGROUND: Aim of this invasive study was to characterize and quantify changes in left ventricular (LV) systolic function due to sequential biventricular pacing (BV) as compared to right atrial triggered simultaneous BV (BV(0)), LV, and right ventricular (RV) pacing in patients with congestive heart failure (CHF). METHODS: In 22 CHF patients, all in sinus rhythm, temporary multisite pacing was performed prior to implantation of a permanent system. LV systolic function was evaluated invasively by the maximum rate of LV pressure increase (dP/dt(max)). Sequential BV pacing was performed with preactivation of either ventricle at 20-80 ms. RESULTS: In comparison to RV pacing, LV and BV(0) pacing increased dP/dt(max) by 33.9 +/- 19.3% and 34.0 +/- 22.6%, respectively (P < 0.001). In 9 patients, optimized sequential BV pacing further improved dP/dt(max) by 8.5 +/- 4.8% compared to BV(0) (range 3.3-17.1, P < 0.05). In 10 patients exhibiting a PR interval < or =200 ms, LV pacing was either superior (n = 6) or equal to BV(0) pacing (n = 4). In these 10 patients, LV pacing yielded a 7.4 +/- 8.0% higher dP/dt(max) than BV(0) pacing (P < 0.05). CONCLUSIONS: Using sequential BV pacing, generally with LV preactivation, moderate improvements in LV systolic function can be achieved in selected patients. Baseline PR interval may aid in the selection of the optimum cardiac resynchronization therapy (CRT) mode, favoring LV pacing in patients with a PR interval < or =200 ms.