Abstract Background Elderly patients display higher on clopidogrel platelet reactivity as compared to younger patients. Treatment with prasugrel 5 mg has been shown to provide more predictable and ...homogenous antiplatelet effect, as compared to clopidogrel, suggesting the possibility of reducing ischemic events after an acute coronary syndrome (ACS) without increasing bleeding. Study design The Elderly-ACS 2 study is a multicenter, randomized, parallel-group, open-label trial designed to demonstrate the superiority of a strategy of dual antiplatelet treatment using a reduced 5 mg daily dose of prasugrel over a standard strategy with a daily clopidogrel dose of 75 mg in patients >74 years of age with ACS (either ST- or non ST-elevation myocardial infarction) undergoing early percutaneous revascularization. The primary endpoint is the composite of all-cause mortality, myocardial re-infarction, disabling stroke and re-hospitalization for cardiovascular causes or bleeding within one year. Taking advantage of the planned size of 2000 patients, the secondary objective is to assess the prognostic impact of selected pre-randomization variables (age, sex, diabetic status, serum creatinine level, ECG changes, abnormal troponin levels, basal and residual SYNergy between percutaneous coronary intervention with TAXus and cardiac surgery SYNTAX score). Conclusion The Elderly-ACS 2 study is a multicenter, randomized trial comparing a strategy of dual antiplatelet therapy with a reduced dose of prasugrel with a standard dose of clopidogrel in elderly patients with ACS undergoing percutaneous revascularization. (The Elderly ACS 2 trial: NCT01777503 )
Abstract The combination of aspirin and a P2Y12 receptor inhibitor is the cornerstone of treatment in patients with acute coronary syndromes (ACS) and in those undergoing percutaneous coronary ...intervention (PCI). At the present time, three different oral P2Y12 receptor inhibitors are available on the market; two have obtained the indication for ACS (clopidogrel and ticagrelor) and one for ACS with planned PCI (prasugrel). An intravenous direct acting P2Y12 inhibitor, cangrelor, has also been recently approved by US and European regulatory agencies for patients undergoing PCI. Although the correct timing and modality of transition from intravenous cangrelor to oral P2Y12 inhibitors is still controversial and needs further evidence, switching between oral P2Y12 receptor inhibitors frequently occurs in clinical practice for several reasons. This practice raises the question of the relative safety of this strategy and of which switching approaches are preferable. In this article, we review the data on switching antiplatelet treatment strategies with P2Y12 receptor inhibitors, and discuss practical considerations for switching therapies in patients with ACS undergoing PCI.
Inappropriate sinus tachycardia (IST) is characterized by an elevated heart rate (HR) at rest and an exaggerated HR response to physical activity or emotional stress. Beta-blockers and calcium ...channel blockers are the first-line therapy but sometimes are poorly tolerated due to side effects.
The purpose of this study was to evaluate the efficacy and safety of ivabradine, a selective inhibitor of the I(f) current of the sinoatrial node, in patients affected by IST.
Eighteen consecutive symptomatic patients (2 men and 16 women; mean age 45 +/- 15 years) affected by IST were enrolled in the study. Every patient underwent resting ECG, 24-hour Holter ECG, and exercise ECG at baseline and at 3-month and 6-month follow-up.
Sixteen patients (14 women; mean age 41 +/- 14 years) completed the study. Holter ECG assessment showed a significant reduction of medium HR (P <.001) and maximal HR (P <.001, basal vs 3-6 months; P = .02, 3 vs 6 months). Minimal HR slightly decreased at 3 months and then stabilized (P = .49, 3 vs 6 months) despite an increased drug dose. Stress test showed a significant decrease at rest (P <.001) and maximal HR (P <.05), suggesting an increased tolerance to physical stress, which was confirmed by a progressive increase of maximal load reached (>100 W) during stress test at 3 months (75%) and 6 months (85%). One patient was excluded because of phosphenes despite dose lowering, and another patient did not complete the protocol.
Ivabradine could represent an effective and safe alternative to calcium channel blockers and beta-blockers for treatment of IST.
Optical coherence tomography (OCT) has been shown to reliably detect cardiac allograft vasculopathy (CAV). In recent studies performed in adult heart transplant (HTx) recipients, OCT revealed the ...presence of vulnerable plaques and complicated coronary artery lesions, thus challenging the current concept that CAV disease is a diffuse concentric and fibrosing vasculopathy. The aim of our study was to characterize CAV by OCT in a young population of HTx recipients.
We prospectively enrolled 21 young HTx recipients (mean age 27 years, range 22 to 38 years) to undergo OCT of the left anterior descending coronary artery (LAD) in addition to annual CAV screening by coronary angiography and virtual histology intravascular ultrasound (VH-IVUS). Quantitative OCT analysis was performed at the site of maximal intimal thickness (MIT) for each LAD segment.
Patients were 27 years old with a mean time from cardiac transplantation of 14.7 ± 6.8 years. All patients exhibited intimal hyperplasia with an abnormal (>1) intima-to-media ratio. The median (interquartile range) MIT values by OCT were 0.37 (0.22 to 0.54) mm, 0.46 (0.29 to 0.54) mm and 0.34 (0.25 to 0.49) mm in the distal, middle and proximal LAD segments, respectively. Qualitative OCT analysis rarely showed features of vulnerable plaque or complicated lesions. Consistently, at VH-IVUS, the prevalent component at the site of MIT per vessel assessed by OCT was fibrous tissue.
Unlike recent evidence in adult HTx recipients, OCT findings of vulnerable plaque and complicated coronary lesions were found to be rare among late survivors of pediatric HTx.
Abstract Background Screening for asymptomatic left ventricular dysfunction (ALVD) in subjects at risk for heart failure (HF) can affect clinical management. The aim of the present study is to ...examine the role of NT-pro BNP in the diagnosis of ALVD in subjects with hypertension and diabetes from primary care. Methods and Results A total of 1012 subjects with hypertension and/or diabetes and no symptoms or signs of HF were assessed by B-type natriuretic peptide (NT-proBNP) assay and echocardiography. Diastolic dysfunction was present in 368/1012 subjects (36.4%): 327 (32.4%) with mild diastolic dysfunction and 41 (4%) with a moderate-to-severe diastolic dysfunction. Systolic dysfunction was present in 11/1012 (1.1%). NT-proBNP levels were 170 ± 206 and 859 ± 661 pg/mL, respectively, in diastolic and systolic dysfunction and 92 ± 169 in normal subjects ( P < .0001). Pooling moderate-to-severe diastolic with systolic dysfunction, a total of 52 subjects (5.1 %) were obtained: best cutoff value of NT-proBNP was 125 pg/mL (males <67 years: sensitivity Sens 87.5%, specificity Spec 92.7%, negative predictive value NPV 99.5%, positive predictive value PPV 33.3%; females <67 years: Sens 100%, Spec 84.1%, NPV 100%, PPV 33.3%; males ≥67 years: Sens 100%, Spec 77.1%, NPV 100%, PPV 32.5%; females ≥67 years: Sens 100%, Spec 59.9%, NPV 100%, PPV 23%). Conclusions The prevalence of ALVD in subjects at risk for HF is 5.1%. Because of its excellent NPV, NT-proBNP can be used by general practitioners to rule out ALVD in hypertensive or diabetic patients.
Background Cardiac resynchronization therapy (CRT) is ineffective in approximately 30% of recipients, in part due to sub-optimal left ventricular (LV) pacing location. The Quartet LV lead, with 2 ...additional electrodes proximal to conventional bipolar lead electrodes, enables 10 different pacing configurations at four independent LV locations. In a CRT patient cohort, we sought to evaluate the spectrum of echocardiographic and electrocardiographic response over these 10 configurations, to select the optimal one in each patient. Moreover, we sought to evaluate the 6-months clinical and echocardiographic response to a “tailored approach” in which the optimal LV pacing configuration for CRT was determined by echocardiographic measures, QRSd and pacing capture thresholds. Methods Twenty-two consecutive CRT indicated patients were implanted with a quadripolar CRT system (St. Jude Medical). Optimal LV pacing configuration was determined by echocardiographic measures, including velocity time integral (VTI), myocardial performance index (MPI) and mitral regurgitation (MR), and an electrocardiographic measure (QRS duration) during pacing from each of the configurations at pre-discharge. The optimal LV pacing vector was chosen for every patient. Clinical and echocardiographic assessment was repeated after 6 months. Results Various configurations provided different VTI, MPI, MR and QRSd values. Conventional bipolar vectors (ie, D1-M2, D1-RVc, M2-RVc) were rarely associated with the best echocardiographic improvements and provided significantly worse VTI, MR, MPI, and QRSd values than the best configuration for every patient ( P = .005, P = .05 and P = .03 for VTI; P = .01, P = .005 and P = .001 for MPI; P = .003, P = .01 and P = .005 for MR, P > .5, P = .01 and P = .05 for QRSd) Conversely, “unconventional” proximal configurations (ie, making use of P4 and M3 electrodes) were generally characterized by higher acute VTI, MR and MPI improvements. CRT devices were reprogrammed with an “unconventional” LV pacing configuration in 50% of patients. A significant improvement in New York Heart Association class (81%), LV ejection fraction (76%), end-diastolic and end-systolic volumes was observed after 6 months ( P = .02, P < .001, P = .02 and P = .003, respectively). Conclusions In this study, conventional bipolar vectors of quadripolar-CRT were rarely associated with the best echocardiographic improvements. Quadripolar CRT utilizing optimal LV pacing configuration was associated with a significant improvement in New York Heart Association class and LV ejection fraction after 6 months.
Several observational studies, randomized controlled trials, and meta-analyses suggested that pretreatment with clopidogrel in addition to aspirin could reduce the rate of ischemic events, especially ...in the setting of acute coronary syndromes. Newer P2Y12 inhibitors like prasugrel and ticagrelor, which provide faster and stronger platelet inhibition compared with clopidogrel, would enhance the benefits of pretreatment. However, 2 recent randomized trials, A Comparison of Prasugrel at PCI or Time of Diagnosis of Non-ST Elevation Myocardial Infarction and the Administration of Ticagrelor in the Cath Lab or in the Ambulance for New ST Elevation Myocardial Infarction to Open the Coronary Artery studies, aimed at assessing the effects of the timing of administration of novel P2Y12 inhibitors in acute coronary syndromes, failed to meet their primary end points. In this report, we review clinical data on pretreatment with dual oral antiplatelet therapy and comment on some criticisms raised from recent trials.
Abstract Background Prednisone at immunosuppressive doses after stenting has shown remarkable efficacy in reducing ischemic recurrences in nondiabetic patients with high post-procedural levels of ...C-reactive protein; the study aim was to compare the clinical outcome obtained in a control group of patients treated with bare metal stents versus 2 other study groups—bare metal stent plus oral prednisone or drug eluting stents—assuming similar optimal adjunctive medical treatment. Methods Five tertiary Italian hospitals enrolled 375 nondiabetic patients with coronary artery disease and no contraindications to dual antiplatelet treatment or corticosteroid therapy in a randomized, controlled study performed between 2007 and 2009. Patients were allocated into 3 study groups: bare metal stents (controls), bare metal stents followed by a 40-day prednisone treatment, or drug-eluting stents. The primary endpoint was the event-free survival of cardiovascular death, myocardial infarction, and recurrence of ischemia needing repeated target vessel revascularization at 1 year as adjudicated by an independent clinical events committee. Results One-year follow-up was obtained in all patients. Patients receiving bare metal stents alone as compared to those treated with prednisone or drug-eluting stents had lower event-free survival; the primary endpoint was 80.8% in controls compared to 88.0% in the prednisone and 88.8% in the drug-eluting stent groups, respectively ( P = .04 and .006). Conclusion Compared with bare metal stents alone, prednisone treatment after bare metal stents or drug-eluting stent implantation result in a better event-free survival at 1 year.
Acute heart failure syndromes (AHFS) are a major public health problem and present a therapeutic challenge to clinicians. Commonly used agents in the treatment of AHFS include diuretics, vasodilators ...(eg, nitroglycerin, nitroprusside, nesiritide), and inotropes (eg, dobutamine, dopamine, milrinone). Patients admitted to hospital with AHFS and low cardiac output state (AHFS/LO) represent a subgroup with very high inhospital and postdischarge mortality rates. Most of these patients require intravenous inotropic therapy. However, the use of current intravenous inotropes has been associated with risk for hypotension, atrial and ventricular arrhythmias, and possibly increased postdischarge mortality, particularly in those with coronary artery disease. Consequently, there is an unmet need for new agents to safely improve cardiac performance (contractility and/or active relaxation) in this patient population. This article reviews a selection of current and investigational agents for the treatment of AHFS, with a main focus on the high-risk patient population with AHFS/LO.
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