Neutrophil gelatinase-associated lipocalin does not predict acute kidney injury in heart failure.

BACKGROUND: Acute cardiorenal syndrome type 1 (CRS-1) is defined by a rapid cardiac dysfunction leading to acute kidney injury (AKI). Neutrophil gelatinase-associated lipocalin (NGAL) is expressed on the surface of human neutrophils and epithelial cells, such as renal tubule cells, and its serum (sNGAL) and urinary have been used to predict AKI in different clinical settings. AIM: To characterize CRS-1 in a cohort of patients with acute heart diseases, evaluating the potentiality of sNGAL as an early marker of CRS-1. METHODS: We performed a retrospective cohort, multi-centre study. From January 2010 to December 2011, we recruited 202 adult patients admitted to the coronary intensive care unit (CICU) with a diagnosis of acute heart failure or acute coronary syndrome. We monitored the renal function to evaluate CRS-1 development and measured sNGAL levels within 24 h and after 72 h of CICU admission. RESULTS: Overall, enrolled patients were hemodynamically stable with a mean arterial pressure of 92 (82-107) mmHg, 55/202 (27.2%) of the patients developed CRS-1, but none of them required dialysis. Neither the NGAL delta value (AUC 0.40, 95%CI: 0.25-0.55) nor the NGAL peak (AUC 0.45, 95%CI: 0.36-0.54) or NGAL cut-off (≥ 140 ng/mL) values were statistically significant between the two groups (CRS-1 vs no-CRS1 patients). The area under the ROC curve for the prediction of CRS-1 was 0.40 (95%CI: 0.25-0.55) for the delta NGAL value and 0.45 (95%CI: 0.36-0.54) for the NGAL peak value. Finally, in multivariate analysis, the risk of developing CRS-1 was correlated with age > 60 years, urea nitrogen at admission and 24 h-urine output (AUC 0.83, SE = 60.5% SP = 93%), while sNGAL was not significantly correlated. CONCLUSION: In our population, sNGAL does not predict CRS-1, probably as a consequence of the mild renal injury and the low severity of heart disease. So, these data might suggest that patient selection should be taken into account when considering the utility of NGAL measurement as a biomarker of kidney damage.

Causes of death in patients ≥75 years of age with non-ST-segment elevation acute coronary syndrome.

The causes of death within 1 year of hospital admission in patients with non-ST-segment elevation acute coronary syndromes are ill defined, particularly in patients aged ≥75 years. From January 2008 through May 2010, we enrolled 645 patients aged ≥75 years with non-ST-segment elevation acute coronary syndromes: 313 in a randomized trial comparing an early aggressive versus an initially conservative approach, and 332, excluded from the trial for specific reasons, in a parallel registry. Each death occurring during 1 year of follow-up was adjudicated by an independent committee. The mean age was 82 years in both study cohorts, and 53% were men. By the end of the follow-up period (median 369 days, interquartile range 345 to 391), 120 patients (18.6%) had died. The mortality was significantly greater in the registry (23.8% vs 13.1%, p = 0.001). The deaths were classified as cardiac in 94% of the cases during the index admission and 68% of the cases during the follow-up period. Eighty-six percent of the cardiac deaths were of ischemic origin. In a multivariate logistic regression model that included the variables present on admission in the whole study population, the ejection fraction (hazard ratio 0.95, 95% confidence interval 0.94 to 0.97; p <0.001), hemoglobin level (hazard ratio 0.85, 95% confidence interval 0.76 to 0.94; p = 0.001), older age (hazard ratio 1.05, 95% confidence interval 1.01 to 1.10, p = 0.010), and creatinine clearance (hazard ratio 0.99, 95% confidence interval 0.97 to 0.99; p = 0.030) were the independent predictors of all-cause death at 1 year. In conclusion, within 1 year after admission for non-ST-segment elevation acute coronary syndromes, most deaths in patients aged ≥75 years have a cardiac origin, mostly owing to myocardial ischemia.

The impact of drug eluting stents availability on the treatment choice among medical therapy, percutaneous or surgical revascularisation and on 4-year clinical outcome in patients with coronary artery disease: a cohort study.

OBJECTIVE: To investigate the influence of the availability of drug eluting stents (DES) on treatment choice (TC) among medical therapy (MT), coronary by-pass surgery (CABG) or percutaneous coronary interventions (PCI) and the consequent clinical outcomes in patients hospitalised because of coronary artery disease (CAD). DESIGN: Observational study comparing two cohorts hospitalised immediately before, and 3 years after DES availability. SETTING: Thirteen hospitals with cardiology facilities. PATIENTS: 2131 consecutive patients with at least one coronary stenosis >50% at coronary angiography (CA) after exclusion of those with acute myocardial infarction or previous CABG or associated relevant valvular disease. MAIN OUTCOME MEASURES: Treatment choice after CA and 4-year clinical outcomes. RESULTS: TC among MT (27% vs 29.2%), PCI (58.6% vs 55.5%) and CABG (14.5% vs 15.3%) was similar in the DES and bare metal stent (BMS) periods (p = 0.51). At least one DES was implanted in 57% of patients treated with PCI in 2005. After 4 years, no difference in mortality (13.8% vs 13.2%, p = 0.72), hospital admissions for myocardial infarction (6.6% vs 5.2%, p = 0.26), stroke (2.2% vs 1.7%, p = 0.49) and further revascularisations (22.3% vs 19.7%, p = 0.25) were observed in patients enrolled in the DES and BMS periods. Only in patients with Syntax score 23-32 a significant change of TC (p = 0.0002) occurred in the DES versus BMS period: MT in 17.4% vs 31%, PCI in 62.2% vs 35.8%, CABG in 20.3% vs 33.2%, with similar 4-year combined end-point of mortality, stroke, myocardial infarction and further revascularisations (45.3% vs 34.2%, p = 0.087). CONCLUSIONS: Three years after DES availability, the TC in patients with CAD has not changed significantly as well as the 4-year incidence of death, myocardial infarction, stroke and further revascularisations. In subgroup with Syntax score 23-32, a significant increase of indications to PCI was observed in the DES period, without any improvement of the 4-year clinical outcome.

Influence of age on the clinical outcomes of coronary revascularisation for the treatment of patients with multivessel de novo coronary artery lesions: sirolimus-eluting stent vs. coronary artery bypass surgery and bare metal stent, insight from the multicentre randomised Arterial Revascularisation Therapy Study Part I (ARTS-I) and Part II (ARTS-II).

AIMS: We sought to evaluate the prognostic impact of age on the procedural results and subsequent clinical outcomes in patients with multivessel disease (MVD) treated either by coronary artery bypass surgery (CABG) or by percutaneous coronary intervention (PCI) with or without drug eluting stents, based on data of the Arterial Revascularisation Therapies Study (ARTS) part I and part II. The potential influence of age in determining the most appropriate revascularisation strategy for patients with MVD is largely unknown. METHODS AND RESULTS: Three year clinical outcome of ARTS I patients randomised to PCI with bare metal stent (BMS) (n= 600) or CABG (n= 605), and matched patients treated by PCI with sirolimus-eluting stents (SES) in ARTS II (n= 607) were reviewed according to four age quartiles. Endpoints were measured in terms of major adverse cardiac and cerebrovascular events MACCE) during hospital stay and up to three years. The frequency of female, diabetes, hypertension, peripheral vascular disease, pulmonary disease, as well as lesion complexity increased with age. At three years, MACCE free survival was comparable between patients treated by CABG or SES PCI, regardless of age quartile. The incidence of MACCE was higher among ARTS I BMS treated patients in all but the second age quartile. This was primarily related to a higher need for repeat revascularisation among BMS treated patients. However, age, which emerged as a strong independent predictor of MACCE following CABG (p<0.005), was not predictive of adverse events following PCI. Conversely, diabetes was the strongest independent predictor of MACCE among PCI treated patients (p<0.02), but didn't affect three-year outcomes following CABG. CONCLUSIONS: Age seems to influence the CABG outcome in-hospital but not PCI. PCI-SES could offer lower immediate risk in patients with MVD and comparable long-term outcome as CABG especially in older patients. The worst outcome of PCI-BMS group is primarily related to the need for repeat revascularisation. Diabetes is the most important predictor of MACCE following PCI.

Primary percutaneous coronary intervention in 'early' latecomers with ST-segment elevation acute myocardial infarction: the role of the infarct-related artery status.

A high proportion of patients with ST-segment elevation myocardial infarction (STEMI) are evaluated more than 12 h after symptom onset. In this setting, current guidelines suggest that mechanical reperfusion should be considered for patients with clinical and/or electrocardiographic evidence of ongoing ischaemia, re-infarction, cardiogenic shock, haemodynamic instability, or documented ejection fraction less than 40% and serious ventricular arrhythmias. Moreover, some adjunctive aspects like the stuttering course of acute myocardial infarction, the chance of an existing coronary collateral circulation, the ischaemic preconditioning and the infarct-related artery patency should be taken into consideration for patients with STEMI presenting from 12 to 72 h after symptom onset. These patients are known as 'early' latecomers. The aim of the present review is to summarize the current knowledge of the pathophysiology related to this topic and to suggest some new indications for primary percutaneous coronary intervention in 'early' latecomers.

Heart-kidney biomarkers in patients undergoing cardiac stress testing.

We examined association of inducible myocardial perfusion defects with cardiorenal biomarkers, and of diminished left ventricular ejection fraction (LVEF) with kidney injury marker plasma neutrophil gelatinase-associated lipocalin (NGAL). Patients undergoing nuclear myocardial perfusion stress imaging were divided into 2 groups. Biomarkers were analyzed pre- and poststress testing. Compared to the patients in the low ischemia group (n = 16), the patients in the high ischemia group (n = 18) demonstrated a significantly greater rise in cardiac biomarkers plasma BNP, NT-proBNP and cTnI. Subjects were also categorized based on pre- or poststress test detectable plasma NGAL. With stress, the group with no detectable NGAL had a segmental defect score 4.2 compared to 8.2 (P = .06) in the detectable NGAL group, and 0.9 vs. 3.8 (P = .03) at rest. BNP rose with stress to a greater degree in patients with detectable NGAL (10.2 vs. 3.5 pg/mL, P = .03). LVEF at rest and with stress was significantly lower in the detectable NGAL group; 55.8 versus 65.0 (P = .03) and 55.1 vs. 63.8 (P = .04), respectively. Myocardial perfusion defects associate with biomarkers of cardiac stress, and detectable plasma NGAL with significantly lower LVEF, suggesting a specific heart-kidney link.

Efficacy and safety of catheter ablation versus antiarrhythmic drugs for atrial fibrillation: a meta-analysis of randomized trials.

BACKGROUND: Atrial fibrillation is the most common arrhythmia in clinical practice. Its treatment is still widely debated due to the large variety of therapeutic options. Radiofrequency catheter ablation (RFCA) around pulmonary vein ostia and in the left atrium has been proposed as a technique to cure atrial fibrillation and is now performed with increasing success worldwide. However, few randomized controlled trials (RCTs) are available. Some of these have been published recently and are not yet included in meta-analyses. OBJECTIVES: We conducted a meta-analysis to summarize the current evidence base for the efficacy and safety of RFCA in patients with atrial fibrillation. METHODS: We searched electronic databases for relevant RCTs comparing RFCA with antiarrhythmic drugs for the management of atrial fibrillation. Recurrence of any atrial tachyarrhythmia (including atrial fibrillation, atrial flutter and atrial tachycardia) and rate of complications and adverse events were the end-points of the analysis. The results are reported as relative risk and 95% confidence interval, calculated using RevMan 5. RESULTS: A total of eight RCTs were identified including 844 patients. Overall, 98 (23.2%) of 421 patients in the treatment group and 324 (76.6%) of 423 patients in the control group had atrial tachyarrhythmia recurrence. RFCA decreased atrial tachyarrhythmia recurrence by 71% (relative risk 0.29, 95% confidence interval 0.20-0.41, P < 0.00001, with random effects model). Fewer complications and adverse events were reported in the ablation group compared with the control group (relative risk 0.72, 95% confidence interval 0.40-1.30, P = 0.28, with random effects model). CONCLUSION: In selected patients with atrial fibrillation, RFCA is a relatively effective and well-tolerated procedure to cure atrial fibrillation. Even though the results of our systematic review favour ablation therapy, large, well-designed RCTs are needed to confirm the efficacy and safety of RFCA for the management of atrial fibrillation.

Spontaneous dissections of coronary arteries and acute coronary syndromes: rationale and design of the DISCOVERY, a multicenter prospective registry with a case-control group.

BACKGROUND: Spontaneous coronary artery dissection (SCAD) is an unusual cause of acute myocardial ischemia that in almost 50% of cases is followed by sudden death. The increasing frequency of SCAD diagnosis may reflect the widespread use of coronary angiography and percutaneous coronary interventions in acute coronary syndromes (ACS). The incidence of SCAD is estimated between 0.1 and 0.28% of all ACS or sudden deaths evaluated by angiography or by anatomical examination, respectively. Most published data available so far deal with single case reports and probably the real incidence of this disease is underestimated. Some predisposing conditions to SCAD are well known and include Marfan syndrome, pregnancy and peripartum state, drug abuse and some anatomical abnormalities of the coronary arteries like aneurysms and severe kinking. The most appropriate therapeutic approach to SCAD is still controversial and decision making is often based on the clinical presentation, extent of dissection and amount of ischemic myocardium. OBJECTIVES AND METHODS: The purpose of this multicenter prospective registry, named DISCOVERY (DISsection of COronary arteries: Veneto and Emilia RegistrY), with a case-control group is to try to assess the role of SCAD in the pathogenesis of ACS. The primary endpoint is the occurrence of major adverse cardiovascular events related to the therapeutic strategy in the acute phase and in the mid-term follow-up. The secondary endpoints are the estimation of the prevalence of SCAD in the pathogenesis of ACS, the association or disassociation of SCAD with presumptive predisposing factors, the appreciation of the timing and extent of multivessel involvement when present, the occurrence of vascular and ocular comorbidities (i.e. carotid dissection and ocular lens abnormalities), the evaluation of the immediate success and the mid-term outcome of percutaneous coronary interventions and the definition of the role of intravascular ultrasound in diagnosis and treatment of SCAD. The enrollment of approximately 50 patients with SCAD is planned. A planned control group of patients of comparable age, sex and clinical presentation will allow us to identify potential peculiar or specific aspects of SCAD in any phase of the disease. CONCLUSION: The DISCOVERY multicenter registry, with a case-control group, is the first large prospective study aimed at assessing the role of SCAD in the pathogenesis of ACS and at identifying the role of different therapeutic strategies in this unusual, multifaceted and probably underestimated pathologic condition.

'Bail-out' bivalirudin use in patients with thrombotic complications unresponsive to conventional treatment during percutaneous coronary intervention.

Percutaneous coronary intervention (PCI) is routinely performed in patients with non-ST elevation acute coronary syndromes after pretreatment with clopidogrel and periprocedural administration of unfractionated heparin on a weight-adjusted basis. Although activated clotting time (ACT) monitoring is encouraged to verify the adequacy of anticoagulation during the procedures, this is not a common practice in many laboratories. The authors describe 4 cases of patients with bifurcation lesions involving the left anterior descending coronary artery, who developed periprocedural thrombosis with acute transmural ischemia. All patients had inadequate ACT measurements, despite conventional heparin dosage and ongoing clopidogrel treatment. In order to achieve complete anticoagulation, patients were switched to bivalirudin, which determined a prompt effect on measured ACT. This therapeutic regimen, coupled with further intervention, allowed resolution of the thrombotic complication without bleeding. This report suggests the feasibility of a strategy of bivalirudin use in patients who have some degree of heparin 'resistance' in the setting of complicated PCI.

Radiofrequency ablation of drug-refractory atrial fibrillation: an observational study comparing 'ablate and pace' with pulmonary vein isolation.

AIMS: To compare clinical characteristics, procedure complexity, acute and long-term outcome of 'ablate and pace' (A&P) with pulmonary vein isolation (PVI) in patients with drug-refractory atrial fibrillation (AF). So far, only few small studies have compared the two procedures. METHODS AND RESULTS: We analysed retrospectively a cohort of symptomatic consecutive patients with drug-refractory AF. Group 1 included 100 patients treated with A&P and Group 2 included 144 patients treated with PVI. Group 1 patients were older (74 +/- 8 vs. 56 +/- 9 years; P < 0.0001), had lower left ventricular ejection fraction (50 +/- 13% vs. 59 +/- 7%; P < 0.05), and a lower prevalence of paroxysmal AF (46% vs. 65%; P < 0.05). Acute success was not statistically different (98% vs. 92.3%, P = ns). Group 1 patients had shorter procedure time and lower radiation exposure with respect to Group 2 patients (70 +/- 15 vs. 204 +/- 58 min, and 8 +/- 4 vs. 57 +/- 22 min; P < 0.0001, respectively). After a median follow-up of 29 months (I, III quartile; 15, 40 months) vs. 25 months (I, III quartile; 8, 36 months) (P = ns), all the patients in Group 1 were free of symptomatic AF, while 113 patients (79%) of Group 2 were in stable sinus rhythm (P < 0.0001). Persistent or permanent AF has been documented in 58 patients (58%) of Group 1 vs. 11 (8%) of Group 2 (P < 0.0001). CONCLUSION: In this series (i) patients treated with A&P and PVI for drug-refractory AF showed significant differences in clinical profile; (ii) A&P is a shorter and less complex procedure, but is associated with a higher rate of persistent AF; (iii) symptomatic recurrences of paroxysmal AF were more frequent in PVI group. Randomized studies appear necessary to identify the best strategy in selected cases.

Acute haemodynamic effects of intra-aortic balloon pump and cardiac resynchronization therapy.

We report two cases in which intra-aortic balloon pump (IABP) was used successfully as a bridge to cardiac resynchronization therapy (CRT) to treat patients with refractory systolic heart failure. The study was designed to assess the acute haemodynamic effects of IABP coupled with CRT using standard haemodynamic monitoring. In both cases, a marked elevation of V-wave in pulmonary capillary wedge pressure (PCWP) was shown, and a moderate-to-severe functional mitral regurgitation was observed. IABP and CRT resulted in a significant acute improvement in aortic pressure, PCWP, and V-wave amplitude compared with baseline measurements and IABP alone. These results provide a basis for studies examining the haemodynamic effects of IABP support associated with CRT in patients with heart failure refractory to medical therapy.

Right ventricular function predicts transplant-free survival in idiopathic dilated cardiomyopathy.

BACKGROUND: Right ventricular function may be reduced in patients with idiopathic dilated cardiomyopathy (IDC). The prognostic implications of right ventricular dysfunction have not been investigated in this group of patients. METHODS: In a series of 120 consecutive patients with IDC [defined as a left ventricular ejection fraction (LVEF) < 55%, normal coronary arteries and no other causes for left ventricular dysfunction], right ventricular function was prospectively evaluated by means of angiocardiography at the time of catheterization. A head-to-head comparison of ventricular volumes, ejection fraction, end-diastolic pressure, stroke work index and end-systolic pressure/volume ratio of the left and right ventricle was performed according to the Cox's proportional hazard method for the pre-defined end-point of transplant-free survival. RESULTS: In the study population, LVEF was 31 +/- 11% and right ventricular ejection fraction (RVEF) was 34 +/- 10%. After a mean follow-up of 30 months (range 12-120 months), 26 patients died (22%) and 14 (12%) underwent heart transplantation. At univariate analysis, all the above mentioned parameters were significantly (P < 0.0001) associated with outcome except left and right ventricular end-systolic pressure/volume ratio. At multivariate analysis, independent predictors of transplant-free survival were RVEF (P = 0.001), right ventricular stroke work index (P = 0.015), right ventricular end-diastolic volume (P = 0.034) and left ventricular end-diastolic volume (P = 0.048), but not LVEF. The same relation holds true considering the end point of total mortality. CONCLUSIONS: Parameters of right ventricular function are strong predictors of survival in IDC, even in patients enrolled over a wide range of LVEFs. The present study suggests that right ventricular function should be evaluated in patients with IDC. A large non-invasive based study on right ventricular function in IDC appears to be warranted.

Abciximab in ST-elevation acute myocardial infarction occurring in a heart transplant recipient and treated with stenting.

The authors describe primary coronary intervention consisting of direct stenting after abciximab administration in a case of acute anterior myocardial infarction occurring in a heart transplant recipient with triple-vessel disease. Primary success was obtained and the patient survived to a one-year angiographic follow up which showed persistent coronary patency. This is the first report concerning the use of abciximab in primary stenting for acute myocardial infarction in allograft coronary artery disease.

Effects of cardiac resynchronization therapy on disease progression in patients with congestive heart failure.

BACKGROUND: Cardiac resynchronization therapy (CRT) represents a new therapeutic modality of proven efficacy for selected patients with heart failure and ventricular asynchrony. The aim of this study was to assess the effects of CRT on clinical variables and cardiac remodeling in patients with moderate-to-severe congestive heart failure and inter/intraventricular conduction delays. METHODS: Thirty-seven patients (32 males, 5 females, mean age 73 +/- 7 years), in NYHA functional class III-IV, with left ventricular ejection fraction (LVEF) < or = 35%, QRS > or = 150 ms, and left ventricular end-diastolic diameter (LVEDD) > or = 55 mm, underwent CRT by biventricular pacing (InSync, InSync III, InSync ICD; Medtronic Inc.). Fourteen (37.8%) had a previous pacemaker, and 11 (29.7%) were in permanent atrial fibrillation. The QRS width, NYHA functional class, LVEDD, left ventricular end-systolic diameter (LVESD), left ventricular end-diastolic volume (LVEDV), left ventricular endsystolic volume (LVESV), and LVEF were retrospectively evaluated in the period before CRT. For the purposes of the present study, the pre-CRT period was divided in two: T(-2) (from 6 to 3 years) and T(-1) (from 3 years to CRT). Moreover, these parameters were measured at the time of CRT (T0) and prospectively in the post-CRT follow-up (Tp). RESULTS: Before CRT, a progressive worsening of the parameters was observed. The QRS duration steadily increased from T(-2) to T(-1) and T0 (both p = 0.000). The NYHA functional class increased from T(-2) to T(-1) and T0 (both p = 0.000). LVEDD and LVESD also increased and were higher at T(-1) (p = 0.001 and p = 0.000, respectively) and at T0 (both p = 0.000) compared to T(-2). Similar results were observed for LVEDV and LVESV. Finally, LVEF was higher at T(-2) than T(-1) and T0 (both p = 0.000). After CRT, there was a reduction in the QRS duration and an improvement in the NYHA functional class compared to T0 (both p = 0.000). LVEDD and LVESD were also reduced (p = 0.005 and p = 0.016, respectively), LVEDV and LVESV decreased (both p = 0.000), and LVEF increased (p = 0.000) with respect to T0. A highly significant correlation was found between LVEDD and LVESD both in the pre- and post-CRT time intervals, with a non-significant difference between the two linear regression lines. Similar results were obtained for the correlations between LVEDV and LVESV. CONCLUSIONS: Congestive heart failure is associated with a progressive widening of the QRS complex and a worsening of the clinical status and results in anatomic remodeling with deterioration of the left ventricular function. CRT induces opposite changes in QRS duration, clinical status, and left ventricular remodelling.

Frequency and determinants of direct stenting in routine percutaneous coronary interventions: data on 835 consecutive procedures in a single center.

BACKGROUND: Recent studies evaluated the technique of direct coronary stenting as compared to stenting-after-predilation in selected anatomic and clinical settings. However, the impact of direct stenting in routine interventional practice remains poorly elucidated. METHODS: From April 1999 to March 2001, all percutaneous coronary interventions performed at our Center were prospectively analyzed to determine the frequency of direct stenting, the success rate and the variables associated with its utilization. RESULTS: 1151 lesions were treated in 835 procedures. Stenting was attempted in 835/1151 lesions (72.5%), 309 (37%) with direct stenting and 526 (63%) with stenting-after-predilation. Direct stenting was successful in 300/309 (97%) and stenting-after-predilation in 515/526 (98%). The success rate of direct stenting was significantly lower in small vessels (< or = 2.75 mm) (89.2 vs 98.5%, p = 0.005). Patients treated with direct stenting were younger (63 +/- 11 vs 65 +/- 11 years, p = 0.024). Direct stenting was preferentially used in saphenous vein grafts and at the ostium of the left anterior descending coronary artery, while it was avoided in bifurcation lesions and with increasing calcium burden. Operators with a caseload > 140 interventions per year were significantly more likely to perform direct stenting than less experienced operators (p = 0.017). In direct stenting, the total contrast medium and the fluoroscopy and procedural times were all significantly (p < 0.0001) lower than those observed in case of stenting-after-predilation. CONCLUSIONS: Direct coronary stenting is currently performed in about one third of the overall caseload. Variables pertaining to the operator's experience, lesion morphology and length, vessel size, and the clinical presentation are all important factors determining the selection of candidates suitable for direct stenting.

Chemotherapy-related cardiotoxicity: new diagnostic and preventive strategies.

Chemotherapy is an established approach for several malignancies, but its utility may be hampered by induced cardiac toxicity possibly leading to heart failure, with a negative impact on the patient's quality of life and ultimately survival. Prospective left ventricular systolic function monitoring has demonstrated that cardiotoxicity could be subclinically present for many months or years before its overt manifestation. Although considered irreversible, some reports suggested recovery or delayed progression of cardiac dysfunction by preventive cardioactive therapies. Thus, the identification of earlier instrumental or biochemical markers of cardiac injury able to predict heart failure remains a major task. Diastolic indexes as a primary expression of hemodynamic dysfunction after cardiac damage, analyzed by means of conventional or newer Doppler technologies (tissue Doppler, color M-mode, etc.) are discussed. Moreover, brain natriuretic peptides, troponins and endothelin-1, as possible sensitive/specific markers/predictors of subclinical cardiotoxicity are reviewed in order to update and possibly improve the strategy for the detection and clinical management of chemotherapy-related cardiotoxic effects.

Safety and efficacy evaluation of clopidogrel compared to ticlopidine after stent implantation: an updated meta-analysis.

BACKGROUND: Combination therapy with aspirin plus ticlopidine has become the reference antithrombotic therapy after coronary stenting. However despite its effectiveness, ticlopidine is associated with a significant incidence of severe side effects. Thus, clopidogrel, a ticlopidine analogue with an excellent safety profile, has been introduced in clinical practice. To date only a few, underpowered studies comparing the clinical efficacy of clopidogrel and aspirin versus standard combination therapy after coronary stenting have been performed and the odds ratios (OR) vary substantially among them. The purpose of the present investigation was to update the data regarding this issue by means of a formal meta-analysis. METHODS: Ten studies were considered suitable for analysis. The OR were calculated for 30 days of follow-up in patients who had undergone successful coronary stenting. Primary endpoints were a composite of death and non-fatal myocardial infarction (MI) (efficacy endpoint) as well as a composite of major adverse side effects (safety endpoint) as considered in every single study. Secondary endpoints were a composite of major adverse cardiac events, according to single study definition, and individual cardiac events as well. RESULTS: Overall, 11688 patients were included. At 30 days, the OR for death and non-fatal MI was 0.63 (95% confidence interval-CI 0.47 to 0.85, p = 0.003) in favor of patients treated with clopidogrel and aspirin. There was also a trend toward less major adverse cardiac events (OR 0.83, 95% CI 0.66 to 1.03, p = 0.1), less mortality (OR 0.70, 95% CI 0.40 to 1.25, p = 0.2), and less non-fatal MI (OR 0.76, 95% CI 0.54 to 1.07, p = 0.1). Furthermore, OR for major adverse side effects was 0.53 (95% CI 0.42 to 0.66, p < 0.00001) in favor of clopidogrel. Similarly, drug intolerance was significantly reduced by clopidogrel (OR 0.51, 95% CI 0.36 to 0.72, p < 0.0001). Fewer patients on clopidogrel developed neutropenia or thrombocytopenia (OR 0.58, 95% CI 0.18 to 1.81, p = 0.3), while the incidence of severe bleeding was similar in the two groups (OR 1.19, 95% CI 0.71 to 1.99, p = 0.5). CONCLUSIONS: The present meta-analysis demonstrates that clopidogrel reduces the 30-day combined endpoint of death and non-fatal MI, thereby showing a superior clinical efficacy compared to ticlopidine in patients who had undergone successful coronary stenting. A significantly better safety profile than ticlopidine was also reported, confirming on a larger scale the findings of randomized comparative trials.

Association of cholesterol levels and occurrence of angiographically detectable endothelial disruption during coronary angioplasty.

BACKGROUND: Disruption of the atherosclerotic plaque is a common feature of both acute coronary syndromes and balloon dilatation of coronary artery stenoses. HYPOTHESIS: The study was undertaken to evaluate whether the known association of cholesterol levels and acute coronary syndromes also exists for the occurrence of angiographically detectable endothelial disruption (ED) following coronary angioplasty. METHODS: For this purpose, we examined 79 consecutive patients (men/women 58/21; mean age: 62 +/- 11 years), with a noncalcified, de novo, significant stenosis in a single native coronary artery, undergoing elective coronary intervention because of stable effort angina. Coronary angioplasty was performed using regular balloon catheters, aiming for a balloon/ artery ratio of 1, with stent implantation allowed only provisionally. Following balloon dilatation, patients were divided into two groups according to the presence or absence of angiographically detectable ED. RESULTS: Endothelial disruption occurred in 28 patients (35%). The two groups with and without ED were comparable with respect to clinical, angiographic, and procedural parameters. A history of hypercholesterolemia was significantly more frequent in patients with ED (93 vs. 2%; p < 0.001). Total and low-density lipoprotein (LDL) cholesterol levels were significantly higher in the group with ED (230.1 +/- 46.5 vs. 204.4 +/- 30.2 mg/dl, p < 0.05; and 150.6 +/- 39.2 vs. 125.8 +/- 26 mg/dl, p < 0.03, respectively). A cut-off value of LDL cholesterol > or = 135 mg/dl identified patients at higher risk of developing ED. CONCLUSION: High cholesterol levels appear to favor the occurrence of ED during coronary angioplasty. Aggressive lipid-lowering therapy and a more careful procedural approach may be warranted in patients with hypercholesterolemia undergoing coronary interventions in order to decrease the occurrence of ED and the associated clinical (acute ischemia) and procedural (stent implantation) consequences.

Systematic coronary stenting after failed thrombolysis in high-risk patients with acute myocardial infarction: procedural results and long-term follow-up.

BACKGROUND: Stenting in acute myocardial infarction (AMI) represents a feasible and effective revascularization strategy. However, very little information is available for patients who receive a stent after failed thrombolysis (so-called 'rescue' stenting). METHODS: We analysed the procedural results and the 2-year follow-up of all consecutive patients with moderate-to-large AMI treated with rescue stenting in the period 1996-2001. RESULTS: The study cohort includes 123 patients (mean age 60+/-12 years, 78% men). Coronary angiography showed multivessel disease in 47% of patients; the infarct-related vessel was the left anterior descending coronary artery in 47%, the right coronary artery in 41%, the left circumflex coronary artery in 9.5% and a saphenous vein graft in 2.5%. Baseline Thrombolysis in Myocardial Infarction (TIMI) flow was grade 0-1 in 65% and grade 2 in 25%. Coronary stenting was attempted in all 123 patients and was successful in 119 out of 123 (96.7%); abciximab was used in 57 out of 123 (46%) and intra-aortic balloon pumping in 35 out of 123 (28%). At the end of the procedure, TIMI 3 flow was obtained in 104 out of 123 (85%) and TIMI 2 flow in 14 out of 123 (11%). There were 10 in-hospital deaths and four late deaths, with a long-term survival of 88.6%. This figure increases to 95.2% if patients presenting with cardiogenic shock are excluded. A new revascularization procedure was performed in 21% of discharged patients (in the target vessel for 12% and in non-target vessels for 9%). Overall, event-free survival at 2 years was 69%. At multivariate analysis, independent predictors of survival were age (P=0.014) and ejection fraction (P=0.006). CONCLUSIONS: This report represents one of the first series concerning long-term follow-up after rescue stenting. The main results include a high procedural feasibility, a low late mortality and a target vessel revascularization rate in the range expected with stenting. These data must be viewed as part of the constant effort to optimize revascularization strategies in AMI.