Association between coffee or tea consumption and cardiovascular outcomes in patients with stable coronary artery disease: Analysis from the CLARIFY registry.

BACKGROUND: Conflicting data exist on the association between consumption of coffee or tea and cardiovascular outcomes, and few focus on patients with established coronary artery disease. AIM: To describe the association between coffee or tea consumption and cardiovascular outcomes in patients with stable coronary artery disease, using an extensive contemporary international registry, allowing the identification of multiple potential confounders. METHODS: The Prospective Observational Longitudinal Registry of Patients With Stable Coronary Artery Disease (CLARIFY) registry enrolled in 2009 and 2010 in 45 countries, with a 5-year follow-up. Patients were categorized according to daily consumption of coffee or tea, and were compared with those declaring neither. The primary composite outcome of myocardial infarction, stroke or cardiovascular death was analysed at 5years, as well as all-cause mortality. Sensitivity analyses were performed with a multivariable model. RESULTS: A total of 15,459 and 10,029 patients declared coffee or tea consumption, respectively. At 5years, after full adjustment, no association was found between coffee consumption and the primary outcome: hazard ratio 1.04 (95% confidence interval 0.89-1.21) for 1 cup; 0.94 (0.82-1.08) for 2-3 cups; and 1.04 (0.86-1.27) for ≥4 cups (P=0.51). Drinking tea was not associated with a different incidence of the primary outcome before or after adjustment, with fully adjusted hazard ratios of 1.08 (95% confidence interval 0.84-1.38) for 1 cup, 1.12 (0.96-1.31) for 2-3 cups and 0.95 (0.79-1.14) for ≥4 cups (P=0.30). After full adjustment, neither coffee nor tea drinking was associated with all-cause mortality. CONCLUSIONS: In outpatients with stable coronary artery disease, there was no association between coffee or tea consumption and ischaemic outcomes or all-cause mortality.

The journey of omega-3 fatty acids in cardiovascular medicine.

In subjects with cardiovascular risk factors or in patients in need of secondary prevention, hypertriglyceridemia is a well-defined risk factor for adverse cardiac events. Drugs containing n-3 polyunsaturated fatty acids (n-3 PUFAs) are approved for treatment of hypertriglyceridemia. In 1999, a cardioprotective effect in post infarct patients was suggested by a large multicentre study, the GISSI prevention trial. The hypothesized mechanism of action was an antiarrhythmic action leading to reduction of the sudden death. However, such a cardioprotective effect of n-3 PUFAs has not been straightforward like for other cardiovascular drugs such as aspirin, statins or ACE inhibitors. On the contrary, it has been a long journey with several ups and downs. Recently, the European Medicines Agency (EMA) has not confirmed the risk benefit of low dose of n-3 PUFA in preventing outcomes after a myocardial infarction. Since the EMA decision, the use of a high dose (4g daily) of pure and stable EPA in a multicentre, international trial, the REDUCE-IT study showed a clear cardiovascular event reduction which was not confirmed in another trial, the STRENGTH study, which utilized 4g daily of an EPA+DHA mixture. It follows that the OMEGA-3 fatty acid story seems to be endless and the last word on cardiovascular benefits cannot be pronounced. We report a brief narrative of an entire journey from the beginning to nowadays.

Mindfulness-Based stress reduction in early palliative care for people with metastatic cancer: A mixed-method study.

OBJECTIVES: To explore the impact of a Mindfulness-Based Stress Reduction (MBSR) intervention for people with metastatic cancer integrated in Early Palliative Care (EPC). DESIGN: Mixed-method study. SETTINGS/LOCATION: EPC Service integrated with Oncology Unit, Carpi General Hospital, Italy from January to October 2017. The MBSR intervention took place inside the hospital. SUBJECTS: Study participation was offered to 25 consecutive people referred to the EPC service. INCLUSION CRITERIA: people with metastatic cancer between 18 and 75 years old; informed consent. EXCLUSION CRITERIA: Performance Status <60% according to Karnofsky scale; active psychiatric disorder. 20 patients were included in the study. INTERVENTION: The adapted program consists of 8 meetings for 2.5 h once a week, a 4.5 h session between the 6th and 7th weeks and 0.5 h home practice daily. The following mindfulness practices were included during the training: formal sitting meditation, body scan, light yoga, walking meditation, and Aikido exercises. Participants were provided with materials for home practice. A qualified MBSR instructor conducted the program. Sessions were attended by a clinical psychologist and a physician trained in meditation, together with the palliative nurse as facilitators. OUTCOME MEASURES: Feasibility and acceptability were assessed on 16 participants. In addition, pre-post measures of cancer pain and mood state were collected. Semi-structured, in-depth interviews were conducted on a subset of 8 participants at the end of the study and analysed using the Interpretative-Phenomenological approach. RESULTS: MBSR attendance to meetings and adherence to home practice were 75%. MBSR intervention helped participants to develop an accepting attitude in respect to metastatic cancer disease helping them to face anxiety and cancer pain. MBSR improves self-regulation of mood state engendering feelings of compassion MBSR program supports participants in questioning and reconnecting with their values and spiritual beliefs. CONCLUSIONS: A Mindfulness intervention integrated into EPC setting is feasible, well accepted and could help metastatic cancer patients to control cancer pain together with an opportunity of emotional and spiritual relief.

C/EBPα mediates the growth inhibitory effect of progestins on breast cancer cells.

Steroid hormones are key gene regulators in breast cancer cells. While estrogens stimulate cell proliferation, progestins activate a single cell cycle followed by proliferation arrest. Here, we use biochemical and genome-wide approaches to show that progestins achieve this effect via a functional crosstalk with C/EBPα. Using ChIP-seq, we identify around 1,000 sites where C/EBPα binding precedes and helps binding of progesterone receptor (PR) in response to hormone. These regions exhibit epigenetic marks of active enhancers, and C/EBPα maintains an open chromatin conformation that facilitates loading of ligand-activated PR. Prior to hormone exposure, C/EBPα favors promoter-enhancer contacts that assure hormonal regulation of key genes involved in cell proliferation by facilitating binding of RAD21, YY1, and the Mediator complex. Knockdown of C/EBPα disrupts enhancer-promoter contacts and decreases the presence of these architectural proteins, highlighting its key role in 3D chromatin looping. Thus, C/EBPα fulfills a previously unknown function as a potential growth modulator in hormone-dependent breast cancer.

Inhaled corticosteroid/long-acting bronchodilator treatment mitigates STEMI clinical presentation in COPD patients.

BACKGROUND: Patients with myocardial infarction and concomitant COPD are at increased risk of poor clinical outcomes, including death, as compared to patients without COPD. AIM: To investigate and compare the severity of the clinical presentation of ST-segment elevation myocardial infarction (STEMI) and of the short-(7days) and long-term-(end of follow up) mortality in COPD patients treated with inhaled corticosteroids (ICS)/long-acting bronchodilator (LABD) - either long-acting beta2 agonist (LABA) or long-acting muscarinic antagonist (LAMA) - vs. any other inhaled treatments. METHODS: Data from the REAL (Registro Angioplastiche dell'Emilia-Romagna) Registry were obtained from a large prospective study population of 11,118 patients admitted to hospital for STEMI. RESULTS: From January 2003 to June 2009 we identified 2032 COPD patients admitted to hospital for STEMI. Eight hundred and twenty (40%) COPD patients were on ICS/LABD treatment (of which 55% on ICS/LABA) prior to admission. After adjustment for potential confounding factors, ICS/LABD treatment before STEMI was an independent predictor of reduced risk of pulmonary oedema and cardiogenic shock (OR 0.5, 95%CI 0.3-0.72, p<0.01; OR 0.7, 95%CI 0.4-0.9, p=0.03, respectively). ICS/LABD treatment was associated to reduced 7-days mortality (OR 0.54, 95%CI 0.29-0.98, p=0.045) compared to other inhaled regimens. ICS/LABD-treated did not affect long-term (median 4years) mortality. After hospital discharge, the proportion of ICS/LABD treated patients decreased significantly at 6months and afterwards after the STEMI episode. CONCLUSION: Our data provide preliminary evidence that in COPD patients ICS/LABD treatment reduces the severity of STEMI acute-phase clinical manifestations compared to other inhaled treatments.

Mindfulness-based stress reduction in patients with interstitial lung diseases: a pilot, single-centre observational study on safety and efficacy.

BACKGROUND: Chronic, progressive respiratory symptoms are associated with great psychological and emotional impact in patients suffering from interstitial lung disease (ILD). This single-centre pilot study evaluated for the first time the safety, feasibility and efficacy of a Mindfulness Based Stress Reduction Program (MBSR) in a group of patients with ILD. METHODS: Prospective observational study set in a university hospital ILD outpatient clinic. Nineteen patients with different ILDs were recruited 2 months prior to the start of the 8-week MBSR program and followed up for 12 months. Primary outcomes were program safety and feasibility, while secondary outcomes were changes in moods and stress (assessed by Profile Of Mood State (POMS) and Perceived Stress Scale (PSS) questionnaires), symptoms (Shortness Of Breath (SOB) and Cough And Sputum Assessment (CASA-Q) questionnaires), lung function and exercise tolerance at 12 months. RESULTS: Two patients (10.5%) dropped out in the observational period before the start of the MBSR intervention because of non-respiratory causes. All 17 patients who entered the 8-week MBSR program managed to complete it with an adherence average of eight sessions of nine. No adverse events related to the mindfulness training were reported. Statistically significant improvements in the POMS total score and in several individual items of POMS and PSS were observed throughout the study. However, respiratory questionnaire scores, lung function and exercise tolerance did not show a significant difference over time. CONCLUSIONS: An MBSR program appears to be safe and feasible in patients with ILD, and might affect perceived moods and stress producing a positive and lasting improvement in several stress-related negative domains. These findings pave the way to larger (possibly multicentre), randomised, controlled confirmatory trials.

Revising common beliefs in the management of stable CAD.

New findings published in 2012 have challenged common beliefs about stable coronary artery disease. Studies have shown that ß-blockers and n-3-polyunsaturated fatty acids have no impact on prognosis, that percutaneous coronary intervention is not always the best option, and that women do not have worse cardiovascular outcomes than men.

Three-year follow-up of the MULTIcentre evaluation of Single high-dose Bolus TiRofiban versus Abciximab with Sirolimus-eluting STEnt or Bare-Metal Stent in Acute Myocardial Infarction StudY (MULTISTRATEGY).

BACKGROUND: The Multicentre Evaluation of Single high-dose Bolus TiRofiban versus Abciximab with Sirolimus-eluting Stent or Bare Metal Stent in Acute Myocardial Infarction Study [MULTISTRATEGY]) randomised 745 patients with ST-elevation myocardial infarction to receive high-dose bolus (HDB) tirofiban or abciximab infusion and sirolimus-eluting (SES) or uncoated-stent (BMS) implantation. Tirofiban was non-inferior to abciximab in terms of ST-segment resolution after intervention, whereas 8 month-major adverse cardiac events occurred in 14.5% in the BMS and 7.8% in the SES groups (P = 0.0039), reflecting a reduction of reintervention rates (10.2% vs. 3.2%). A three-year follow-up was performed to extend previous short- to mid-term findings. METHODS AND RESULTS: Complete data at 3 years was available for 736 patients (99%). All-cause mortality was 6.7% in the tirofiban and 7.8% in the abciximab (P = 0.56) and 7.5% in the BMS vs 7.0 in the SES groups, P = 0.79. The composite of all-cause death or MI was identical at 12.9% in tirofiban and abciximab groups, P = 0.99 and it occurred in 13.2% in the BMS vs. 12.6% in the SES groups (P = 0.83). The need for reintervention remained more than twice as common with BMS (13.7%; versus 6.2%, P = 0.0006). The cumulative rate of stent thrombosis (ST) did not differ. This is inspite of a higher very late definite, probable or possible ST thrombosis rate in the SES group. CONCLUSIONS: The 3-year follow-up of MULTISTRATEGY demonstrated comparable outcomes with HDB Tirofiban or abciximab and a sustained efficacy of SES to reduce reintervention with no difference in death, repeat MI or ST.

Sex-specific benefits of sirolimus-eluting stent on long-term outcomes in patients with ST-elevation myocardial infarction undergoing primary percutaneous coronary intervention: insights from the Multicenter Evaluation of Single High-Dose Bolus Tirofiban Versus Abciximab With Sirolimus-Eluting Stent or Bare-Metal Stent in Acute Myocardial Infarction Study trial.

OBJECTIVES: We assessed the relation between female sex and sirolimus-eluting stent (SES) use on long-term outcomes in acute myocardial infarction. BACKGROUND: There are no data on sex-specific differences in long-term benefit of SES use compared with bare-metal stent (BMS) use among patients undergoing primary percutaneous coronary interventions. METHODS: We performed a post hoc analysis of the MULTISTRATEGY trial. Hazard ratios (HRs) of events with 95% CI for sex and stent type were computed using Cox proportional regression with adjustment for confounders. RESULTS: A total of 744 patients, 64 years old (55-73 years old), 179 (24.1%) women, were enrolled. After a follow-up of 1,080 days, SES use was associated with a significant reduction of major adverse cardiovascular events, that is, the composite of all-cause death, reinfarction, or clinically driven target vessel revascularization (TVR) (13.9% vs 23.6%, adjusted HR 0.62, 95% CI 0.41-0.94, P = .026) and of TVR (6.1% vs 15.1%, adjusted HR 0.35, 95% CI 0.19-0.63, P < .001) in men. Conversely, SES use was not associated to a better outcome among women (major adverse cardiovascular events 21.9% in SES vs 18.2% in the BMS group, adjusted HR 1.27, 95% CI 0.53-3.02, P = .59; TVR 6.6% vs 9.1%, adjusted HR 0.62, 95% CI 0.17-2.21, P = .46). CONCLUSIONS: In this analysis, the clinical benefit of SES use, over BMS, at 3-year follow-up was restricted to men and was not observed among women.

Persistent coronary no flow after wire insertion is an early and readily available mortality risk factor despite successful mechanical intervention in acute myocardial infarction: a pooled analysis from the STRATEGY (Single High-Dose Bolus Tirofiban and Sirolimus-Eluting Stent Versus Abciximab and Bare-Metal Stent in Acute Myocardial Infarction) and MULTISTRATEGY (Multicenter Evaluation of Single High-Dose Bolus Tirofiban Versus Abciximab With Sirolimus-Eluting Stent or Bare-Metal Stent in Acute Myocardial Infarction Study) trials.

OBJECTIVES: These studies sought to investigate the impact on mortality of coronary flow after passage of the wire through the culprit vessel in patients with ST-segment elevation myocardial infarction (STEMI) undergoing mechanical reperfusion. BACKGROUND: Reduced spontaneous coronary flow before percutaneous coronary intervention influences mortality in patients with STEMI. Response to vessel wiring in patients with an occluded coronary artery before intervention might further discriminate outcomes irrespective of pre- and post-intervention coronary flow. METHODS: Data from the STRATEGY (Single High-Dose Bolus Tirofiban and Sirolimus-Eluting Stent Versus Abciximab and Bare-Metal Stent in Acute Myocardial Infarction) and MULTISTRATEGY (Multicenter Evaluation of Single High-Dose Bolus Tirofiban Versus Abciximab With Sirolimus-Eluting Stent or Bare-Metal Stent in Acute Myocardial Infarction Study) trials were pooled: of 919 index procedures, 902 films (98%) were technically adequate for core laboratory TIMI (Thrombolysis In Myocardial Infarction) flow determination. RESULTS: TIMI flow grade 0 was present before percutaneous coronary intervention in 59% of infarct vessels, TIMI flow grade 1 to 2 was found in 21%, whereas the remainder of infarct arteries presented with TIMI flow grade 3. In 49% of patients who showed persistent TIMI flow grade 0 after wire insertion (AWI), mortality was higher at 30 days (5.3%) and 1 year (9.4%) compared with patients in whom TIMI flow grade before percutaneous coronary intervention was either >0 (0.8%; p < 0.003 and 3.6%, p < 0.008) or improved from 0 AWI (1.5%, p < 0.04 and 3.6%, p < 0.02). After correcting for multiple imbalances, including baseline and final flow, persistent TIMI flow grade 0 AWI remained associated at 30 days to 2-fold (risk ratio [RR]: 2.1, 95% confidence interval [CI]: 1.08 to 5.00; p = 0.038) and at 1 year to almost 3-fold increases of mortality (RR: 2.7, 95% CI: 1.3 to 5.6; p = 0.008). CONCLUSIONS: STEMI patients displaying persistent no-flow AWI have a lower survival rate despite an apparently successful mechanical intervention. As an early marker for high residual mortality risk, persistent no-flow AWI may qualify STEMI patients for dedicated pharmacomechanical treatment strategies.

Randomized comparison of 6- versus 24-month clopidogrel therapy after balancing anti-intimal hyperplasia stent potency in all-comer patients undergoing percutaneous coronary intervention Design and rationale for the PROlonging Dual-antiplatelet treatment after Grading stent-induced Intimal hyperplasia study (PRODIGY).

BACKGROUND: The optimal duration of clopidogrel therapy after coronary stenting is debated because of the scarcity of randomized controlled trials and inconsistencies arising from registry data. Although prolonged clopidogrel therapy after bare metal stenting is regarded as an effective secondary prevention measure, the safety profile of drug-eluting stents itself has been questioned in patients not receiving ≥ 12 months of dual-antiplatelet therapy. HYPOTHESIS: Twenty-four months of clopidogrel therapy after coronary stenting reduces the composite of death, myocardial infarction, or stroke compared with 6 months of treatment. STUDY DESIGN: PRODIGY is an unblinded, multicenter, 4-by-2 randomized trial. All-comer patients with indication to coronary stenting are randomly treated-balancing randomization-with bare metal stent (no active late loss inhibition), Endeavor Sprint zotarolimus-eluting stent (Medtronic, Santa Rosa, CA) (mild late loss inhibition), Taxus paclitaxel-eluting stent (Boston Scientific, Natick, MA) (moderate late loss inhibition), or Xience V everolimus-eluting stent (Abbott Vascular, Santa Clara, CA) (high late loss inhibition). At 30 days, patients in each stent group are randomly allocated to receive 24 or up to 6 months of clopidogrel therapy-primary end point randomization. With 1,700 individuals, this study will have >80% power to detect a 40% difference in the primary end point after sample size augmentation of 5% and a background event rate of 8%. SUMMARY: The PRODIGY trial aims to assess whether 24 months of clopidogrel therapy improves cardiovascular outcomes after coronary intervention in a broad all-comer patient population receiving a balanced mixture of stents with various anti-intimal hyperplasia potency.

Clinical synergy of perindopril and calcium-channel blocker in the prevention of cardiac events and mortality in patients with coronary artery disease. Post hoc analysis of the EUROPA study.

BACKGROUND: The purposes of the study were to determine the effects of addition of perindopril to long-term continuous treatment with calcium-channel blocker (CCB) on cardiac outcomes in the stable coronary artery disease (CAD) population of EUROPA and to explore the presence of synergy between perindopril and CCB in secondary prevention. METHODS: We identified participants receiving CCB at every visit during the 4.2-year follow-up and analyzed the effect of addition of perindopril (n = 1,022 perindopril/CCB vs n = 1,100 placebo/CCB). RESULTS: Addition of perindopril to CCB significantly reduced total mortality by 46% (P < .01 vs placebo) and primary end point (a composite of cardiovascular mortality, nonfatal myocardial infarction, and resuscitated cardiac arrest) by 35% (P < .05 vs placebo). There were 41%, 54%, and 28% reductions in cardiovascular mortality, hospitalization for heart failure, and myocardial infarction, respectively. Comparison of hazard ratios suggests the presence of a clinical synergy between perindopril and CCB, with a greater effect than addition of individual effects. CONCLUSION: Addition of perindopril to CCB in stable CAD patients had a significant supplementary impact on cardiac outcomes and mortality.

Noncontact mapping of left ventricle during CRT implant.

INTRODUCTION: Not all candidates for cardiac resynchronization therapy (CRT) are responders at follow-up. Echocardiographic parameters of dyssynchrony do not predict the response. Analysis of electrical properties of left ventricle (LV) by noncontact mapping (NCM) could be useful to better identify candidates for CRT. METHODS AND RESULTS: We studied nine consecutive patients undergoing CRT. An NCM was positioned in the LV via atrial transeptal puncture. LV activation was recorded during sinus rhythm (SR), pacing from RV, from different LV epicardial locations, and in biventricular (BIV) pacing. The corresponding invasive pressure was determined. Heparin, administered during NCM, was reversed and CRT implant was completed. An offline analysis of the data was performed in order to measure transeptal and total LV activation time, to evaluate the site of earliest and latest LV activation, and the pattern of activation. No complications occurred. Mean time of total NCM procedures was 24 + or - 7 minutes. During SR, RV, LV, and BIV pacing, respectively, a "U"-shaped LV activation pattern was found in three, seven, four, and and two patients; mean LV activation time was 58.1 + or - 7.0, 81.7 + or - 15.8, 71.1 + or - 12.4, and 65.6 + or - 7.7 ms; and mean systolic LV peak pressure was 114 + or - 21, 97 + or - 18, 103 + or - 17 and 110 + or - 15 mmHg, respectively. LV activation was influenced by a slow conduction area at the pacing site and by the duration of transeptal time. CONCLUSION: An NCM during CRT is safe and feasible. It provides an additional information on electrical activation in SR and in various modality of pacing. Further studies with larger populations are needed in order to correlate electrical to clinical outcomes.

Optimizing the treatment of hypertension and stable coronary artery disease: clinical evidence for fixed-combination perindopril/amlodipine.

BACKGROUND: Optimized management of hypertension and coronary artery disease (CAD) improves cardiovascular risk and outcomes, and prevents complications. This article reviews evidence for the fixed combination of the angiotensin-converting enzyme (ACE) inhibitor perindopril and the calcium channel blocker amlodipine. METHODS: A literature search was performed in PubMed/MEDLINE to identify articles published in English between 1988 and March 2008 describing clinical trials, particularly outcome trials, or mechanisms of therapeutic action relevant to the use of combination therapy in patients with hypertension or stable coronary artery disease with an ACE inhibitor (perindopril) and a calcium channel blocker (amlodipine). FINDINGS: Clinical trials indicate that this combination may have a positive impact on cardiovascular mortality and morbidity in hypertensive individuals. The two complementary mechanisms of action appear to work in synergy, leading to more efficient blood pressure lowering, improved fibrinolytic function, and reduction of secondary effects. This also represents a simplified management strategy for stable CAD. Perindopril has proven efficacy in the prevention of cardiovascular events and mortality in CAD patients, while amlodipine is widely used in the symptomatic management of CAD. Both aspects of guideline-recommended management of CAD are therefore addressed in a single tablet. CONCLUSIONS: The clinical evidence for fixed-combination perindopril/amlodipine indicates it as a credible option for the optimization of the management of hypertension and CAD.

Comparison of angioplasty with infusion of tirofiban or abciximab and with implantation of sirolimus-eluting or uncoated stents for acute myocardial infarction: the MULTISTRATEGY randomized trial.

CONTEXT: Abciximab infusion and uncoated-stent implantation is a complementary treatment strategy to reduce major adverse cardiac events in patients undergoing angioplasty for ST-segment elevation myocardial infarction (STEMI). It is uncertain whether there may be similar benefits in replacing abciximab with high-dose bolus tirofiban. Similarly, the use of drug-eluting stents in this patient population is currently discouraged because of conflicting results on efficacy reported in randomized trials and safety concerns reported by registries. OBJECTIVE: To evaluate the effect of high-dose bolus tirofiban and of sirolimus-eluting stents as compared with abciximab infusion and uncoated-stent implantation in patients with STEMI undergoing percutaneous coronary intervention. DESIGN, SETTING, AND PATIENTS: An open-label, 2 x 2 factorial trial of 745 patients presenting with STEMI or new left bundle-branch block at 16 referral centers in Italy, Spain, and Argentina between October 2004 and April 2007. INTERVENTIONS: High-dose bolus tirofiban vs abciximab infusion and sirolimus-eluting stent vs uncoated stent implantation. MAIN OUTCOME MEASURES: For drug comparison, at least 50% ST-segment elevation resolution at 90 minutes postintervention with a prespecified noninferiority margin of 9% difference (relative risk, 0.89); for stent comparison, the rate of major adverse cardiac events, defined as the composite of death from any cause, reinfarction, and clinically driven target-vessel revascularization within 8 months. RESULTS: ST-segment resolution occurred in 302 of 361 patients (83.6%) who had received abciximab infusion and 308 of 361 (85.3%) who had received tirofiban infusion (relative risk, 1.020; 97.5% confidence interval, 0.958-1.086; P < .001 for noninferiority). Ischemic and hemorrhagic outcomes were similar in the tirofiban and abciximab groups. At 8 months, major adverse cardiac events occurred in 54 patients (14.5%) with uncoated stents and 29 (7.8%) with sirolimus stents (P = .004), predominantly reflecting a reduction of revascularization rates (10.2% vs 3.2%). The incidence of stent thrombosis was similar in the 2 stent groups. CONCLUSIONS: In patients with STEMI undergoing percutaneous coronary intervention, compared with abciximab, tirofiban therapy was associated with noninferior resolution of ST-segment elevation at 90 minutes following coronary intervention, whereas sirolimus-eluting stent implantation was associated with a significantly lower risk of major adverse cardiac events than uncoated stents within 8 months after intervention. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00229515.

Radiofrequency ablation of atrial fibrillation: is the persistence of all intraprocedural targets necessary for long-term maintenance of sinus rhythm?

BACKGROUND: Several approaches have been developed for radiofrequency catheter ablation of atrial fibrillation, but the correct intraprocedural end point is still under debate, and few data exist about the destiny of ablation lesions over time. The aim of the present study was to evaluate the long-term maintenance of intraprocedural end points of ablation procedures. METHODS AND RESULTS: Inclusion criteria were (1) a previous ablation procedure of pulmonary vein (PV) encircling performed for drug-refractory persistent atrial fibrillation; (2) a "complete" intraprocedural end point, which consisted of voltage abatement inside the lesions, PV disconnection, and exit-block pacing from inside the lesions, attained in all PVs; and (3) stable sinus rhythm documented during a minimum follow-up of 2.5 years after the procedure. Twenty volunteers were selected (12 males, mean age 59+/-7 years) and underwent a repeat electrophysiological study. After a follow-up of 36.4+/-4.7 months, complete voltage abatement was maintained around 32 PVs (40.0%), PV disconnection persisted in 12 (37.5%) of the previously isolated PVs, and exit block was present in 39 PVs (48.7%). Ten patients who underwent a redo ablation procedure because of recurrences of atrial fibrillation were used as the control group. Differences in intraprocedural end-point maintenance between the 2 groups were not statistically significant. CONCLUSIONS: Common intraprocedural end points such as voltage abatement, PV disconnection, and exit block persist only in a limited number of patients, even when the outcome is favorable during follow-up. Further investigation will be required to determine whether such data will have implications for ablation strategies.

Feasibility of the transseptal approach for fast and unstable left ventricular tachycardia mapping and ablation with a non-contact mapping system.

BACKGROUND: Radiofrequency ablation of fast and unstable left ventricular tachycardia (VT) usually requires non-contact mapping. The procedure is usually performed by a retrograde-transaortic route, requiring a double femoral artery puncture, for the 9F multielectrode catheter and the 7F ablation catheter which are advanced through the aorta and aortic valve into the left ventricle (LV). Reported limitations of the procedure are due to the stiffness of the balloon catheter, particularly in patients with tortuous peripheral arteries, atherosclerotic aorta, or with aortic stenosis. The aim of our study was to test the feasibility and assess the safety of a transseptal approach for left VT non-contact mapping and ablation. MATERIALS AND METHODS: Ten patients with multiple cardiac defibrillator shocks because of fast and unstable VT were selected for non-contact mapping and ablation. After a double transseptal puncture the multielectrode catheter (Ensite Array, St. Jude Medical) was advanced through a standard 10F introducer to a stable position in the LV apex over a 260 cm length 0.035 J-tip guidewire. The ablation catheter (Celsius Thermo-cool, Biosense Webster) was then inserted through the second 8F introducer. Twenty-five monomorphic sustained ventricular tachycardia were induced and ablated at the level of the diastolic pathway or exit point revealed by unipolar isopotential mapping. The total procedural and fluoroscopy times were 209 +/- 32 min and 28.5 +/- 9.27 min, respectively, which were comparable to those described with the traditional retrograde-transaortic approach. No major complication related with the transseptal approach were reported. CONCLUSION: A transseptal approach can be a feasible and effective alternative approach for mapping and ablation of fast and unstable left VT with a non-contact mapping system.

Tirofiban and sirolimus-eluting stent vs abciximab and bare-metal stent for acute myocardial infarction: a randomized trial.

CONTEXT: Bare-metal stenting with abciximab pretreatment is currently considered a reasonable reperfusion strategy for acute ST-segment elevation myocardial infarction (STEMI). Sirolimus-eluting stents significantly reduce the need for target-vessel revascularization (TVR) vs bare-metal stents but substantially increase procedural costs. At current European list prices, the use of tirofiban instead of abciximab would absorb the difference in cost between stenting with sirolimus-eluting vs bare-metal stents. OBJECTIVE: To evaluate the clinical and angiographic impact of single high-dose bolus tirofiban plus sirolimus-eluting stenting vs abciximab plus bare-metal stenting in patients with STEMI. DESIGN, SETTING, AND PATIENTS: Prospective, single-blind, randomized controlled study (Single High Dose Bolus Tirofiban and Sirolimus Eluting Stent vs Abciximab and Bare Metal Stent in Myocardial Infarction [STRATEGY]) of 175 patients (median age, 63 [interquartile range, 55-72] years) presenting to a single referral center in Italy with STEMI or presumed new left bundle-branch block and randomized between March 6, 2003, and April 23, 2004. INTERVENTION: Single high-dose bolus tirofiban regimen plus sirolimus-eluting stenting (n = 87) vs standard-dose abciximab plus bare-metal stenting (n = 88). MAIN OUTCOME MEASURES: The primary end point was a composite of death, nonfatal myocardial infarction, stroke, or binary restenosis at 8 months. Secondary outcomes included freedom, at day 30 and month 8, from major cardiac or cerebrovascular adverse events (composite of death, reinfarction, stroke, and repeat TVR). RESULTS: Cumulatively, 14 of 74 patients (19%; 95% confidence interval [CI], 10%-28%) in the tirofiban plus sirolimus-eluting stent group and 37 of 74 patients (50%; 95% CI, 44%-56%) in the abciximab plus bare-metal stent group reached the primary end point (hazard ratio, 0.33; 95% CI, 0.18-0.60; P<.001 [P<.001 by Fischer exact test]). The cumulative incidence of death, reinfarction, stroke, or TVR was significantly lower in the tirofiban plus sirolimus-eluting stent group (18%) vs the abciximab plus bare-metal stent group (32%) (hazard ratio, 0.53; 95% CI, 0.28-0.92; P = .04), predominantly reflecting a reduction in the need for TVR. Binary restenosis was present in 6 of 67 (9%; 95% CI, 2%-16%) and 24 of 66 (36%; 95% CI, 26%-46%) patients in the tirofiban plus sirolimus-eluting stent and abciximab plus bare-metal stent groups, respectively (P = .002). CONCLUSION: Tirofiban-supported sirolimus-eluting stenting of infarcted arteries holds promise for improving outcomes while limiting health care expenditure in patients with myocardial infarction undergoing primary intervention.

Therapeutic effects of L-carnitine and propionyl-L-carnitine on cardiovascular diseases: a review.

Several experimental studies have shown that levocarnitine reduces myocardial injury after ischemia and reperfusion by counteracting the toxic effect of high levels of free fatty acids, which occur in ischemia, and by improving carbohydrate metabolism. In addition to increasing the rate of fatty acid transport into mitochondria, levocarnitine reduces the intramitochondrial ratio of acetyl-CoA to free CoA, thus stimulating the activity of pyruvate dehydrogenase and increasing the oxidation of pyruvate. Supplementation of the myocardium with levocarnitine results in an increased tissue carnitine content, a prevention of the loss of high-energy phosphate stores, ischemic injury, and improved heart recovery on reperfusion. Clinically, levocarnitine has been shown to have anti-ischemic properties. In small short-term studies, levocarnitine acts as an antianginal agent that reduces ST segment depression and left ventricular end-diastolic pressure. These short-term studies also show that levocarnitine releases the lactate of coronary artery disease patients subjected to either exercise testing or atrial pacing. These cardioprotective effects have been confirmed during aortocoronary bypass grafting and acute myocardial infarction. In a randomized multicenter trial performed on 472 patients, levocarnitine treatment (9 g/day by intravenous infusion for 5 initial days and 6 g/day orally for the next 12 months), when initiated early after acute myocardial infarction, attenuated left ventricular dilatation and prevented ventricular remodeling. In treated patients, there was a trend towards a reduction in the combined incidence of death and CHF after discharge. Levocarnitine could improve ischemia and reperfusion by (1) preventing the accumulation of long-chain acyl-CoA, which facilitates the production of free radicals by damaged mitochondria; (2) improving repair mechanisms for oxidative-induced damage to membrane phospholipids; (3) inhibiting malignancy arrhythmias because of accumulation within the myocardium of long-chain acyl-CoA; and (4) reducing the ischemia-induced apoptosis and the consequent remodeling of the left ventricle. Propionyl-L-carnitine is a carnitine derivative that has a high affinity for muscular carnitine transferase, and it increases cellular carnitine content, thereby allowing free fatty acid transport into the mitochondria. Moreover, propionyl-L-carnitine stimulates a better efficiency of the Krebs cycle during hypoxia by providing it with a very easily usable substrate, propionate, which is rapidly transformed into succinate without energy consumption (anaplerotic pathway). Alone, propionate cannot be administered to patients in view of its toxicity. The results of phase-2 studies in chronic heart failure patients showed that long-term oral treatment with propionyl-L-carnitine improves maximum exercise duration and maximum oxygen consumption over placebo and indicated a specific propionyl-L-carnitine effect on peripheral muscle metabolism. A multicenter trial on 537 patients showed that propionyl-L-carnitine improves exercise capacity in patients with heart failure, but preserved cardiac function.

High-dose bolus tirofiban and sirolimus eluting stent versus abiciximab and bare metal stent in acute myocardial infarction (STRATEGY) study--protocol design and demography of the first 100 patients.

BACKGROUND: Primary bare metal stenting and abciximab infusion are currently considered the best available reperfusion strategy for acute ST-segment elevation myocardial infarction (STEMI). Sirolimus eluting stents (SES), compared to bare metal stent (BMS), greatly reduce the incidence of binary restenosis and target vessel revascularisation (TVR), but their use on a routine basis results in a significant increase in medical costs. With current European list prices, the use of tirofiban instead of abciximab would save enough money to absorb the difference between SES and BMS. AIM: To assess whether in patients with STEMI the combination of SES with high dose bolus (HDB) tirofiban results in a similar incidence of major cardiovascular events (MACE) but in a lower binary restenosis rate after six months compared to BMS and abciximab. METHODS AND RESULTS: 160 patients are required to satisfy the primary composite end-point, including MACE and binary restenosis. The study is ongoing: the current paper focuses on the methodology and demography of the first 100 patients so far enrolled. Patients randomised to HDB tirofiban (n = 50, mean age: 62 +/- 12, 40 males) and abciximab (n = 50, mean age: 63 +/- 12, 38 males) do not differ for medical history, presentation profile, medications at discharge, angiographic profile and creatine-kinase MB-fraction at peak. CONCLUSIONS: The results of the trial will be available by the end of 2004: they will be crucial for the cardiologists to know whether the gold standard for AMI treatment should be reconsidered after the introduction of SES into the clinical practice.