Impact of eGFR rate on 1-year all-cause mortality in patients with stable coronary artery disease.

BACKGROUND: Coronary artery disease (CAD) is a leading cause of mortality and is often complicated by chronic kidney disease. We sought to investigate the prevalence of different degree of estimated glomerular filtration rate (eGFR) reduction, the clinical and bio-humoral correlates, its relationship with therapeutic management, and its predictive role on 1-year all-cause mortality, in patients with stable CAD. METHODS: We studied 4,130 patients with stable CAD recruited in a prospective, observational, nationwide study (START, STable coronary Artery diseases RegisTry) in Italy. Baseline clinical characteristics, pharmacological treatment, and all-cause 1-year mortality were evaluated according to groups of eGFR (<30; 30-59; 60-89; ≥90 ml/min/1.73 m2) at baseline. RESULTS: The presence and the degree of chronic kidney disease entailed an unfavorable risk profile, since it was gradually associated with more comorbidities. Furthermore, progressively lower eGFR values were associated to lower diastolic blood pressure and hemoglobin values. As eGFR lowers, optimal medical treatment and its persistence overtime is reduced. Multivariate analysis showed that progressively lower eGFR significantly correlated with all-cause 1-year mortality [hazard ratio (HR): 1.02; 95% confidence intervals (CI): 1.01-1-03; p = 0.0001]. CONCLUSIONS: Low eGFR is associated with an increasing risk of all-cause mortality in patients with stable CAD. Chronic kidney disease may hamper the optimization of treatment limiting the use of drugs which may favorably impact cardiovascular and renal outcomes.

Early Complete Revascularization in Hemodynamically Stable Patients With ST-Segment Elevation Myocardial Infarction and Multivessel Disease.

BACKGROUND: The optimal strategy and timing of revascularization in hemodynamically stable patients with ST-segment elevation myocardial infarction and multivessel disease is unknown. We performed a systematic review and meta-analysis to explore the comparative efficacy and safety of early complete revascularization vs culprit-only or staged revascularization in this setting. METHODS: We searched the literature for randomized clinical trials that assessed this issue. Early complete revascularization was defined as a complete revascularization achieved during the index procedure or within 72 hours. Efficacy outcomes were major adverse cardiovascular events, myocardial infarction, repeat revascularization, and all-cause mortality. Safety outcomes were all bleeding events, stroke, and contrast-induced acute kidney injury. RESULTS: Nine randomized clinical trials with a total of 2837 patients were included; 1254 received early complete revascularization and 1583 were treated with other revascularization strategies. After a mean follow-up of 15.3 ± 9.4 months early complete revascularization was associated with a lower risk of major adverse cardiovascular events (relative risk [RR], 0.51; 95% confidence interval [CI], 0.41-0.62; P < 0.00001; number needed to treat = 8), myocardial infarction (RR, 0.59; 95% CI, 0.40-0.87), and repeat revascularization (RR, 0.39; 95% CI, 0.28-0.55) without any difference in all-cause mortality and in safety outcomes compared with culprit-only or staged revascularization. Moreover, fractional flow reserve-guided complete revascularization reduced the incidence of repeat revascularization compared with angiography-guided procedure (χ2 = 4.36; P = 0.04). CONCLUSIONS: Early complete revascularization should be considered in hemodynamically stable patients with ST-segment elevation myocardial infarction and multivessel disease deemed suitable for percutaneous interventions. Fractional flow reserve-guided complete revascularization might be superior to angiography-guided procedures in reducing need for further interventions.

Closure of patent foramen ovale or medical therapy alone for secondary prevention of cryptogenic cerebrovascular events.

AIMS: About one-third of ischemic stroke are cryptogenic. Paradoxical embolism through patent foramen ovale (PFO) has been identified as a possible cause of cryptogenic stroke. Therefore, PFO closure has been considered for secondary prevention of cryptogenic stroke. However, randomized clinical trials (RCTs) comparing PFO closure versus medical therapy led to conflicting results. Our objectives were to examine if PFO closure is superior to medical therapy alone for secondary prevention of cryptogenic stroke and to investigate whether PFO closure is associated with an increased incidence of atrial fibrillation/atrial flutter (AFL). METHODS: The authors systematically searched MEDLINE for RCTs that compared PFO closure with medical therapy. Efficacy outcome was cerebrovascular event (CVE) recurrence and safety outcome was new-onset atrial fibrillation/AFL. The outcomes of interest were investigated according to device type with subgroup analyses and meta-regression. RESULTS: The authors included eight RCTs constituting 4114 patients. Patients who underwent PFO closure had a lower risk of CVE recurrence compared with medically treated patients [relative risk (RR): 0.56; 95% confidence interval (CI) 0.40-0.80; P = 0.001; I = 30%]. This protective effect was consistent across the different device types. Patients who underwent PFO closure developed more frequently atrial fibrillation/AFL (RR 4.96; 95% CI 2.74-8.99; P < 0.00001; I = 0%), which was mainly transient and within 1 month. Atrial fibrillation/AFL risk was consistent according to device types, although marginally significant in the Amplatzer subgroup. CONCLUSION: PFO closure might have a role in secondary CVE prevention of patients with PFO and cryptogenic stroke. However, it is associated with an increased incidence of new-onset atrial fibrillation/AFL especially within 1 month.

A multidisciplinary consensus document on follow-up strategies for patients treated with percutaneous coronary intervention.

The number of percutaneous coronary interventions (PCI) is increasing worldwide. Follow-up strategies after PCI are extremely heterogeneous and can greatly affect the cost of medical care. Of note, clinical evaluations and non-invasive exams are often performed to low risk patients. In the present consensus document, practical advises are provided with respect to a tailored follow-up strategy on the basis of patients' risk profile. Three strategies follow-up have been defined and types and timing of clinical and instrumental evaluations are reported. Clinical and interventional cardiologists, cardiac rehabilitators, and general practitioners, who are in charge to manage post-PCI patients, equally contributed to the creation of the present document.

Remote ischemic post-conditioning of the lower limb during primary percutaneous coronary intervention safely reduces enzymatic infarct size in anterior myocardial infarction: a randomized controlled trial.

OBJECTIVES: This study sought to evaluate whether remote ischemic post-conditioning (RIPC) could reduce enzymatic infarct size in patients with anterior ST-segment elevation myocardial infarction undergoing primary percutaneous coronary intervention (pPCI). BACKGROUND: Myocardial reperfusion injury may attenuate the benefit of pPCI. In animal models, RIPC mitigates myocardial reperfusion injury. METHODS: One hundred patients with anterior ST-segment elevation myocardial infarction and occluded left anterior descending artery were randomized to pPCI + RIPC (n = 50) or conventional pPCI (n = 50). RIPC consisted of 3 cycles of 5 min/5 min ischemia/reperfusion by cuff inflation/deflation of the lower limb. The primary endpoint was infarct size assessed by the area under the curve of creatinine kinase-myocardial band release (CK-MB). Secondary endpoints included the following: infarct size assessed by cardiac magnetic resonance delayed enhancement volume; T2-weighted edema volume; ST-segment resolution >50%; TIMI (Thrombolysis In Myocardial Infarction) frame count; and myocardial blush grading. RESULTS: Four patients (2 RIPC, 2 controls) were excluded due to missing samples of CK-MB. A total of 96 patients were analyzed; median area under the curve CK-MB was 8,814 (interquartile range [IQR]: 5,567 to 11,325) arbitrary units in the RIPC group and 10,065 (IQR: 7,465 to 14,004) arbitrary units in control subjects (relative reduction: 20%, 95% confidence interval: 0.2% to 28.7%; p = 0.043). Seventy-seven patients underwent a cardiac magnetic resonance scan 3 to 5 days after randomization, and 66 patients repeated a second scan after 4 months. T2-weighted edema volume was 37 ± 16 cc in RIPC patients and 47 ± 22 cc in control subjects (p = 0.049). ST-segment resolution >50% was 66% in RIPC and 37% in control subjects (p = 0.015). We observed no significant differences in TIMI frame count, myocardial blush grading, and delayed enhancement volume. CONCLUSIONS: In patients with anterior ST-segment elevation myocardial infarction, RIPC at the time of pPCI reduced enzymatic infarct size and was also associated with an improvement of T2-weighted edema volume and ST-segment resolution >50%. (Remote Postconditioning in Patients With Acute Myocardial Infarction Treated by Primary Percutaneous Coronary Intervention [PCI] [RemPostCon]; NCT00865722).

Use of IVUS guided coronary stenting with drug eluting stent: a systematic review and meta-analysis of randomized controlled clinical trials and high quality observational studies.

BACKGROUND/OBJECTIVES: Long term safety of DES, particularly regarding thrombosis is of concern. The hypothesized underlying mechanisms (stent under expansion, malapposition) could be prevented by IVUS guidance. Aim of this meta-analysis of randomized controlled clinical trials (RCT) and high quality observational cohort studies (HQ-OBS) is to quantify the potential clinical benefit of intravascular ultrasound (IVUS) guidance in drug-eluting stents (DES) implantation. METHODS: We performed an extensive literature search for full-text articles published in 2003­2013. The primary outcome was the rate of major adverse cardiac events (MACE) in RCT and HQ-OBS; secondary outcomes were death, myocardial infarction (MI), revascularization, thrombosis and post-procedural minimum lumen diameter (MLD). Fixed/random effect relative risks (RRs) or standardized mean difference (SMD) and 95% confidence interval (95% CI) were computed for the meta-analysis. RESULTS: Thirty-four articles were retrieved from 268 found; of these 3 were RCT and 9 were HQ-OBS; 18,707 patients were enrolled, 1037 in RCT and 17,670 in OBS. Median follow-up was 20 months. IVUS guidance was associated with a significantly lower rate of MACE (RR=0.80, 95% CI 0.71­0.89, p b 0.001), death (RR=0.60, 95% CI 0.48­0.74, p b 0.001), MI (RR=0.59, 95% CI 0.44­0.80, p=0.001) and thrombosis (RR=0.50, 95% CI 0.32­0.80, p=0.007) and larger MLD (SMD=0.15, 95% CI 0.03 to 0.27, p=0.014), but not of revascularization (RR=0.95, 95% CI 0.82­1.09, p=0.75). CONCLUSIONS: In this meta-analysis, IVUS guidance in DES implantation appears to reduce MACE, mortality and MI, possibly by reducing thrombosis rather than restenosis rate. Patients at high risk for thrombosis might be identified as the best candidate for IVUS guidance.

Economic impact of remote patient monitoring: an integrated economic model derived from a meta-analysis of randomized controlled trials in heart failure.

AIMS: To assess the cost-effectiveness and the cost utility of remote patient monitoring (RPM) when compared with the usual care approach based upon differences in the number of hospitalizations, estimated from a meta-analysis of randomized clinical trials (RCTs). METHODS AND RESULTS: We reviewed the literature published between January 2000 and September 2009 on multidisciplinary heart failure (HF) management, either by usual care or RPM to retrieve the number of hospitalizations and length of stay (LOS) for HF and for any cause. We performed a meta-analysis of 21 RCTs (5715 patients). Remote patient monitoring was associated with a significantly lower number of hospitalizations for HF [incidence rate ratio (IRR): 0.77, 95% CI 0.65-0.91, P < 0.001] and for any cause (IRR: 0.87, 95% CI: 0.79-0.96, P = 0.003), while LOS was not different. Direct costs for hospitalization for HF were approximated by diagnosis-related group (DRG) tariffs in Europe and North America and were used to populate an economic model. The difference in costs between RPM and usual care ranged from €300 to €1000, favouring RPM. These cost savings combined with a quality-adjusted life years (QALYs) gain of 0.06 suggest that RPM is a 'dominant' technology over existing standard care. In a budget impact analysis, the adoption of an RPM strategy entailed a progressive and linear increase in costs saved. CONCLUSIONS: The novel cost-effectiveness data coupled with the demonstrated clinical efficacy of RPM should encourage its acceptance amongst clinicians and its consideration by third-party payers. At the same time, the scientific community should acknowledge the lack of prospectively and uniformly collected economic data and should request that future studies incorporate economic analyses.

High-dose erythropoietin in patients with acute myocardial infarction: a pilot, randomised, placebo-controlled study.

BACKGROUND: Mortality and morbidity after acute myocardial infarction (AMI) remain high even when myocardial reperfusion is successful. Erythropoietin (EPO) protects against experimental MI. METHODS: The aim of this single-centre study was to investigate the effects of short-term high-dose erythropoietin on peripheral blood cells (PBCs) and infarct size in 30 patients with a first uncomplicated AMI undergoing percutaneous coronary intervention (PCI) who were randomly assigned to treatment with EPO (33 × 10(3)IU before PCI, and 24 and 48 h after admission), or placebo. We considered short-term CD34+ cell mobilisation, quantitative PBC gene expression in the apoptotic, angiogenic and inflammatory pathways, and enzymatically estimated infarct size. Echocardiographic and cardiac magnetic resonance studies were performed in the acute phase and six months later. RESULTS: CD34+ cell mobilisation 72 h after admission was greater in the EPO-treated patient group (93 cells/µl [36-217] vs 22 cells/µl [6-51]; p = 0.002), who also showed higher expression of the anti-apoptotic AKT and NFkB, the pro-angiogenic VEGFR-2, and the EPO-R genes, and lower expression of the pro-apoptotic CASP3 and TP53 and pro-inflammatory IL12a genes. Moreover, they showed smaller infarct size (30% reduction in CK-MB release; p = 0.025), and a favourable pattern of left ventricular remodelling. CONCLUSIONS: Short-term high-dose EPO administration in patients with AMI treated by PCI and standard anti-platelet therapy increases the levels of circulating CD34+ cells, shifts PBC gene expression towards anti-apoptotic, pro-angiogenic and anti-inflammatory pathways, and decreases infarct size. The clinical relevance of these results needs to be confirmed in specifically tailored trials.

Regional abnormalities of myocardial deformation in patients with hypertrophic cardiomyopathy: correlations with delayed enhancement in cardiac magnetic resonance.

AIMS: Hypertrophic cardiomyopathy (HCM) is a genetic disease histologically characterized by a profound disarray of myocardial fibres and by local fibrosis. We sought to characterize regional left ventricular contractility in HCM patients using deformation analysis and to compare it with the presence or absence of delayed enhancement in cardiac magnetic resonance (CMR). METHODS AND RESULTS: We studied 58 HCM patients (mean age 41 years, 37 male). The control population comprised 15 normal subjects. Colour tissue-Doppler imaging was acquired in two-dimensional mode from apical four-chamber and two-chamber views; off-line analysis was performed in four basal and four middle left ventricular segments. Gadolinium-enhanced CMR was performed in 36 HCM patients. In HCM patients, peak systolic strain was not uniform across left ventricular segments; differences were not related to site or thickness of the segment analysed. Paradoxically, positive systolic strain values were measured in six middle segments. Delayed CMR enhancement was associated with lower peak systolic strain (P = 0.007). Regional non-uniformities in peak systolic strain were not observed in normal subjects. CONCLUSION: Areas of reduced left ventricular contractility in deformation analysis are associated with delayed CMR enhancement in patients with HCM.

Usefulness of cardiac magnetic resonance in assessing the risk of ventricular arrhythmias and sudden death in patients with hypertrophic cardiomyopathy.

AIMS: To assess the relationship between cardiovascular magnetic resonance (CMR) parameters and both spontaneous ventricular tachycardia (VT) and risk of sudden cardiac death (SCD) in hypertrophic cardiomyopathy (HCM) patients. METHODS AND RESULTS: One hundred and eight consecutive HCM patients (mean age 42 +/- 15 years, 76% males) underwent CMR evaluation and risk assessment. Delayed contrast enhancement (DCE) was quantified with a specifically designed score. Endpoints were either the presence of clinical VT/ventricular fibrillation (VF) or of acknowledged risk factors for SCD. Compared to patients without arrhythmia, those with VT/VF (n = 33) had a higher DCE score [median 8 (2-13) vs. 11 (6-20); P = 0.01]; DCE score was also the only independent predictor of VT/VF in the multivariable model. DCE score [median 6 (1-10.5) vs. 12 (6-18); P = 0.001], mean and maximal left ventricular (LV) wall thickness (MaxLVWT), as well as LV mass index were significantly greater among patients at risk for SCD (n = 51) compared with the remaining 57 patients at low risk. DCE score and MaxLVWT were independent predictors of SCD risk. CONCLUSION: In HCM patients several CMR parameters are associated with risk for SCD. A semi-quantitative index of DCE is a significant multivariable predictor of both clinical VT/VF and of risk for SCD and may contribute to risk assessment in borderline or controversial cases.

Barth syndrome associated with compound hemizygosity and heterozygosity of the TAZ and LDB3 genes.

Barth syndrome is an X-linked recessive disorder caused by the tafazzin (TAZ) gene mutations and includes dilated cardiomyopathy (DCM) with left ventricular non-compaction, neutropenia, skeletal myopathy, abnormal mitochondria and 3-methylglutaconic aciduria. Dilated cardiomyopathy with left ventricular non-compaction transmitted as an autosomal dominant condition has also been associated with LIM domain-binding 3 (LDB3) gene defects. We describe a family in which the 12-year-old proband had left ventricular non-compaction and DCM. His mother had five miscarriages, two other sons who died in infancy, and a healthy son and daughter. The proband showed left ventricular non-compaction-DCM, skeletal myopathy, recurrent oral aphthous ulcers and cyclic neutropenia. The DCM progressively improved with age; medical therapy was discontinued at 5 years of age. At present, left ventricular function is normal and arrhythmias are absent. Magnetic resonance imaging documented left ventricular non-compaction. However, oral aphthous ulcers and cyclic neutropenia have recurred. In the proband we identified two novel mutations, one of maternal origin in the TAZ gene (p.[Glu202ValfsX15]) and one of paternal origin in the LDB3 gene (p.[Thr350Ile]). The mother, brother and father are healthy; although the latter two show prominent left ventricle trabeculation without dysfunction. Expression studies of TAZ and LDB3 genes were conducted in family members and controls. In the proband, brother and father, LDB3 expression was similar to control cases. TAZ and LDB3 expression progressively declined with age in control both blood and myocardial samples. However, an endomyocardial biopsy performed in the proband at 6 months of age, showed significantly lower TAZ and LDB3 expression than in age-matched myocardial controls. We believe that the clinical, genetic and expression data support the hypothesis that tafazzins are essential during fetal and early post-natal life.