Infective Endocarditis in the Elderly: Challenges and Strategies.

The specific management of infective endocarditis (IE) in elderly patients is not specifically addressed in recent guidelines despite its increasing incidence and high mortality in this population. The term "elderly" corresponds to different ages in the literature, but it is defined by considerable comorbidity and heterogeneity. Cancer incidence, specifically colorectal cancer, is increased in older patients with IE and impacts its outcome. Diagnosis of IE in elderly patients is challenging due to the atypical presentation of the disease and the lower performance of imaging studies. Enterococcal etiology is more frequent than in younger patients. Antibiotic treatment should prioritize diminishing adverse effects and drug interactions while maintaining the best efficacy, as surgical treatment is less commonly performed in this population due to the high surgical risk. The global assessment of elderly patients with IE, with particular attention to frailty and geriatric profiles, should be performed by multidisciplinary teams to improve disease management in this population.

EpCAM and microvascular obstruction in patients with STEMI: a cardiac magnetic resonance study.

INTRODUCTION AND OBJECTIVES: Microvascular obstruction (MVO) is negatively associated with cardiac structure and worse prognosis after ST-segment elevation myocardial infarction (STEMI). Epithelial cell adhesion molecule (EpCAM), involved in epithelium adhesion, is an understudied area in the MVO setting. We aimed to determine whether EpCAM is associated with the appearance of cardiac magnetic resonance (CMR)-derived MVO and long-term systolic function in reperfused STEMI. METHODS: We prospectively included 106 patients with a first STEMI treated with percutaneous coronary intervention, quantifying serum levels of EpCAM 24hours postreperfusion. All patients underwent CMR imaging 1 week and 6 months post-STEMI. The independent correlation of EpCAM with MVO, systolic volume indices, and left ventricular ejection fraction was evaluated. RESULTS: The mean age of the sample was 59±13 years and 76% were male. Patients were dichotomized according to median EpCAM (4.48 pg/mL). At 1-week CMR, lower EpCAM was related to extensive MVO (P=.021) and larger infarct size (P=.019). At presentation, EpCAM values were significantly associated with the presence of MVO in univariate (OR, 0.58; 95%CI, 0.38-0.88; P=.011) and multivariate logistic regression models (OR, 0.55; 95%CI, 0.35-0.87; P=.010). Although MVO tends to resolve at chronic phases, decreased EpCAM was associated with worse systolic function: reduced left ventricular ejection fraction (P=.009) and higher left ventricular end-systolic volume (P=.043). CONCLUSIONS: EpCAM is associated with the occurrence of CMR-derived MVO at acute phases and long-term adverse ventricular remodeling post-STEMI.

Coronary Revascularization and Long-Term Survivorship in Chronic Coronary Syndrome.

Ischemic heart disease (IHD) persists as the leading cause of death in the Western world. In recent decades, great headway has been made in reducing mortality due to IHD, based around secondary prevention. The advent of coronary revascularization techniques, first coronary artery bypass grafting (CABG) surgery in the 1960s and then percutaneous coronary intervention (PCI) in the 1970s, has represented one of the major breakthroughs in medicine during the last century. The benefit provided by these techniques, especially PCI, has been crucial in lowering mortality rates in acute coronary syndrome (ACS). However, in the setting where IHD is most prevalent, namely chronic coronary syndrome (CCS), the increase in life expectancy provided by coronary revascularization is controversial. Over more than 40 years, several clinical trials have been carried out comparing optimal medical treatment (OMT) alone with a strategy of routine coronary revascularization on top of OMT. Beyond a certain degree of symptomatic improvement and lower incidence of minor events, routine invasive management has not demonstrated a convincing effect in terms of reducing mortality in CCS. Based on the accumulated evidence more than half a century after the first revascularization procedures were used, invasive management should be considered in those patients with uncontrolled symptoms despite OMT or high-risk features related to left ventricular function, coronary anatomy, or functional assessment, taking into account the patient expectations and preferences.

Role of antiangiogenic VEGF-A165b in angiogenesis and systolic function after reperfused myocardial infarction.

INTRODUCTION AND OBJECTIVES: Angiogenesis helps to reestablish microcirculation after myocardial infarction (MI). In this study, we aimed to further understand the role of the antiangiogenic isoform vascular endothelial growth factor (VEGF)-A165b after MI and to explore its potential as a coadjuvant therapy to coronary reperfusion. METHODS: Two mice MI models were formed: a) permanent coronary ligation (nonreperfused MI); b) transient 45-minute coronary occlusion followed by reperfusion (reperfused MI); in both models, animals underwent echocardiography before euthanasia at day 21 after MI induction. We determined serum and myocardial VEGF-A165b levels. In both experimental MI models, we assessed the functional and structural role of VEGF-A165b blockade. In a cohort of 104 ST-segment elevation MI patients, circulating VEGF-A165b levels were correlated with cardiovascular magnetic resonance-derived left ventricular ejection fraction at 6 months and with the occurrence of adverse events (death, heart failure, and/or reinfarction). RESULTS: In both models, circulating and myocardial VEGF-A165b levels were increased 21 days after MI induction. Serum VEGF-A165b levels inversely correlated with systolic function evaluated by echocardiography. VEGF-A165b blockade increased capillary density, reduced infarct size, and enhanced left ventricular function in reperfused, but not in nonreperfused, MI experiments. In patients, higher VEGF-A165b levels correlated with depressed ejection fraction and worse outcomes. CONCLUSIONS: In experimental and clinical studies, higher serum VEGF-A165b levels are associated with worse systolic function. Their blockade enhances neoangiogenesis, reduces infarct size, and increases ejection fraction in reperfused, but not in nonreperfused, MI experiments. Therefore, VEGF-A165b neutralization represents a potential coadjuvant therapy to coronary reperfusion.

Coronary Serum Obtained After Myocardial Infarction Induces Angiogenesis and Microvascular Obstruction Repair. Role of Hypoxia-inducible Factor-1A.

INTRODUCTION AND OBJECTIVES: Microvascular obstruction (MVO) exerts deleterious effects following acute myocardial infarction (AMI). We investigated coronary angiogenesis induced by coronary serum and the role of hypoxia-inducible factor-1A (HIF-1A) in MVO repair. METHODS: Myocardial infarction was induced in swine by transitory 90-minute coronary occlusion. The pigs were divided into a control group and 4 AMI groups: no reperfusion, 1minute, 1 week and 1 month after reperfusion. Microvascular obstruction and microvessel density were quantified. The proangiogenic effect of coronary serum drawn from coronary sinus on endothelial cells was evaluated using an in vitro tubulogenesis assay. Circulating and myocardial HIF-1A levels and the effect of in vitro blockade of HIF-1A was assessed. RESULTS: Compared with control myocardium, microvessel density decreased at 90-minute ischemia, and MVO first occurred at 1minute after reperfusion. Both peaked at 1 week and almost completely resolved at 1 month. Coronary serum exerted a neoangiogenic effect on coronary endothelial cells in vitro, peaking at ischemia and 1minute postreperfusion (32 ± 4 and 41 ± 9 tubes vs control: 3 ± 3 tubes; P < .01). Hypoxia-inducible factor-1A increased in serum during ischemia (5-minute ischemia: 273 ± 52 pg/mL vs control: 148 ± 48 pg/mL; P < .01) being present on microvessels of all AMI groups (no reperfusion: 67% ± 5% vs control: 15% ± 17%; P < .01). In vitro blockade of HIF-1A reduced the angiogenic response induced by serum. CONCLUSIONS: Coronary serum represents a potent neoangiogenic stimulus even before reperfusion; HIF-1A might be crucial. Coronary neoangiogenesis induced by coronary serum can contribute to understanding the pathophysiology of AMI.

Dynamics and implications of circulating anti-angiogenic VEGF-A165b isoform in patients with ST-elevation myocardial infarction.

Angiogenesis is crucial to restore microvascular perfusion in the jeopardized myocardium in the weeks following reperfused ST-segment elevation myocardial infarction (STEMI). (VEGF)-A165b, an anti-angiogenic factor, has been identified as a regulator of vascularization; however, it has not been previously implicated in acute myocardial infarction. We sought to investigate the dynamics of circulating VEGF-A165b and its association with cardiac magnetic resonance-derived infarct size and left ventricular ejection fraction (LVEF). 50 STEMI patients and 23 controls were included. Compared with control individuals, serum VEGF-A165b was elevated in STEMI patients prior to primary percutaneous coronary intervention (PCI). Following PCI, serum VEGF-A165b increased further, reaching a maximum level at 24 h and decreased one month after reperfusion. VEGF-A165b levels at 24 h were associated with a large infarct size and inversely related to LVEF. VEGF-A165b expression was increased in myocardial infarct areas from patients with previous history of AMI. An ex vivo assay using serum from STEMI patients showed that neutralization of VEGF-A165b increased tubulogenesis. Overall, the study suggests that VEGF-A165b might play a deleterious role after AMI as an inhibitor of angiogenesis in the myocardium. Accordingly, neutralization of VEGF-A165b could represent a novel pro-angiogenic therapy for reperfusion of myocardium in STEMI.

Improvement in Risk Stratification in Transcatheter Aortic Valve Implantation Using a Combination of the Tumor Marker CA125 and the Logistic EuroSCORE.

INTRODUCTION AND OBJECTIVES: Conventional risk scores have not been accurate in predicting peri- and postprocedural risk of patients undergoing transcatheter aortic valve implantation (TAVI). Elevated levels of the tumor marker carbohydrate antigen 125 (CA125) have been linked to adverse outcomes after TAVI. We studied the additional value of CA125 to that of the EuroSCORE in predicting long-term mortality after TAVI. METHODS AND RESULTS: During a median follow-up of 59 weeks, 115 of 422 patients (27%) died after TAVI. Mortality was higher with elevated CA125 (> 30 U/mL) and EuroSCORE (> median) (47% vs 20%, P<.001 and 38% vs 16%, P<.001, respectively). In the multivariable analysis, CA125 (> 30 U/mL) remained an independent predictor of mortality (hazard ratio [HR], 2.16; 95% confidence interval [95%CI], 1.48-3.15; P<.001) and improved the predictive capability of the model (C-statistic: 0.736 vs 0.731) and the net reclassification index (51% 95%CI, 33-73) with an integrated discriminative improvement of 3.5% (95%CI, 0.5-8.4). A new variable (CA125-EuroSCORE) was created, with the combinations of the 2 possible binary states of these variables (+, elevated, -, not elevated; C1: CA125- EuroSCORE-; C2: CA125+ EuroSCORE-; C3: CA125- EuroSCORE+; C4: CA125+ EuroSCORE+). Patients in C1 exhibited the lowest cumulative mortality rate (14% [26 of 181]). Mortality was intermediate for C2 (CA125 > 30 U/mL and EuroSCORE ≤ median) and C3 (CA125 ≤ 30 U/mL and EuroSCORE > median): 27% (8 of 30) and 28% (37 of 131), respectively. Patients in C4 (CA125 > 30 U/mL and EuroSCORE > median) exhibited the highest mortality (55% [44 of 80], P-value for trend<.001). CONCLUSIONS: CA125 offers additional prognostic information beyond that obtained by the EuroSCORE. Elevation of both markers was associated with a poor prognosis.

Secondary forms of Takotsubo cardiomyopathy: A whole different prognosis.

BACKGROUND: Takotsubo syndrome (TKS) usually mimics an acute coronary syndrome. However, several clinical forms have been reported. Our aim was to assess if different stressful triggers had prognostic influence on TKS, and to establish a working classification. METHODS: We performed an analysis including patients with TKS between 2003-2013 from our prospective local database and the RETAKO National Registry, fulfilling Mayo criteria. Patients were divided in two groups regarding their potential triggers: (a) none/psychic stress as 'primary forms' and (b) physical factors (asthma, surgery, trauma, etc.) as 'secondary forms'. RESULTS: Finally, 328 patients were included, 90.2% women, with a mean age of 69.7 years. Patients were divided into primary TKS (n=265) and 63 secondary TKS groups. Age, gender, previous functional class and cardiovascular risk profile displayed no differences between groups before admission. However, primary-TKS patients suffered a main complaint of chest pain (89.4% vs 50.7%, p<0.0001) with frequent vegetative symptoms. Regarding treatment before admission, there were no differences either. During admission, differences were related to more intensive antithrombotic and anxiolytic drug use in the primary TKS group. Inotropic and mechanical ventilation use was higher in the secondary cohort. After discharge, a more frequent prescription of beta-blockers and statins in primary-TKS patients was seen. Secondary forms displayed more in-hospital stay and evolutive complications: death (hazard ratio (HR): 3.41; 95% confidence interval (CI): 1.14-10.16, p=0.02), combined event variable (MACE) (HR: 1.61; 95% CI: 1.01-2.6, p=0.04) and recurrences (HR: 1.85; 95% CI: 1.06-3.22, p=0.02). CONCLUSION: Secondary TKS could present or mark worse short and long-term prognoses in terms of mortality, recurrences and readmissions. We propose a simple working nomenclature for TKS.

Prognosis and management of acute coronary syndrome in Spain in 2012: the DIOCLES study.

INTRODUCTION AND OBJECTIVES: To identify the current mortality and management of patients admitted for suspected acute coronary syndrome in Spain. The last available registry (2004-2005) reported an in-hospital mortality of 5.7%. METHODS: The study included patients consecutively admitted between January and June 2012 at 44 hospitals selected at random. Information was collected on clinical course at admission and on events at 6 months. RESULTS: A total of 2557 patients admitted with suspected acute coronary syndrome were included: 788 (30.8%) with ST-segment elevation, 1602 (62.7%) without ST-segment elevation, and 167 (6.5%) with unclassified acute coronary syndrome. In-hospital mortality was 4.1% (6.6%, 2.4%, and 7.8% respectively), significantly lower than that observed for 2004-2005. Reperfusion treatment (most commonly, primary percutaneous coronary intervention) was administered to 85.7% of patients with ST-segment elevation attended within 12h. The median time from first medical contact to thrombolysis was 40 min and to balloon inflation, 120 min. Among patients without ST-segment elevation, coronary angiography was performed in 80.6%, percutaneous intervention in 52.0%, and surgery was indicated in 6.4%. Secondary prevention treatments at discharge was prescribed more often than in earlier registries. In patients alive at discharge (follow-up available for 97.1%), 6-month mortality was 3.8%. CONCLUSIONS: Mortality among patients with acute coronary syndrome in Spain was lower than that reported in the most recent published studies, in parallel with a more frequent use of the main treatments recommended.

The appropriate and justified use of medical radiation in cardiovascular imaging: a position document of the ESC Associations of Cardiovascular Imaging, Percutaneous Cardiovascular Interventions and Electrophysiology.

The benefits of cardiac imaging are immense, and modern medicine requires the extensive and versatile use of a variety of cardiac imaging techniques. Cardiologists are responsible for a large part of the radiation exposures every person gets per year from all medical sources. Therefore, they have a particular responsibility to avoid unjustified and non-optimized use of radiation, but sometimes are imperfectly aware of the radiological dose of the examination they prescribe or practice. This position paper aims to summarize the current knowledge on radiation effective doses (and risks) related to cardiac imaging procedures. We have reviewed the literature on radiation doses, which can range from the equivalent of 1-60 milliSievert (mSv) around a reference dose average of 15 mSv (corresponding to 750 chest X-rays) for a percutaneous coronary intervention, a cardiac radiofrequency ablation, a multidetector coronary angiography, or a myocardial perfusion imaging scintigraphy. We provide a European perspective on the best way to play an active role in implementing into clinical practice the key principle of radiation protection that: 'each patient should get the right imaging exam, at the right time, with the right radiation dose'.

Tumor marker carbohydrate antigen 125 predicts adverse outcome after transcatheter aortic valve implantation.

OBJECTIVES: This study sought to predict the value of tumor marker carbohydrate antigen 125 (CA125) before and after transcatheter aortic valve implantation (TAVI) for all-cause death and a composite endpoint of death, admission for heart failure, myocardial infarction, and stroke (major adverse cardiac events [MACE]). BACKGROUND: Risk stratification after TAVI remains challenging. The use of biomarkers in this setting represents an unmet need. METHODS: CA125 was measured in 228 patients before and after TAVI. The association with outcomes was assessed using parametric Cox regression and joint modeling for baseline and longitudinal analyses, respectively. CA125 was evaluated as logarithm transformation and dichotomized by its median value (M1 ≤15.7 U/ml vs. M2 >15.7 U/ml). RESULTS: At a median follow-up of 183 days (interquartile range: 63 to 365) and 144 days (interquartile range: 56 to 365), 50 patients (22%) died and 75 patients (33%) experienced MACE. A 3-fold increase in the rates for death and MACE was observed in patients above the median (M2 vs. M1) of CA125 (5.2 vs. 1.6 per 10 person-years and 8.3 vs. 3.3 per 10 person-years, respectively; p for both <0.001). In a multivariable analysis adjusted for logistic EuroSCORE, New York Heart Association functional class III/IV, and device success, baseline values of CA125 (M2 vs. M1) independently predicted death (hazard ratio [HR]: 2.18; 95% confidence interval [CI]: 1.11 to 4.26; p = 0.023) and MACE (HR: 1.77; 95% CI: 1.05 to 2.98; p = 0.031). In the longitudinal analysis, lnCA125 as a time-varying exposure, was highly associated with both endpoints: HR: 1.47; 95% CI: 1.01 to 2.14; p = 0.043 and HR: 2.26; 95% CI: 1.28 to 3.98; p = 0.005, for death and MACE, respectively. CONCLUSIONS: Serum levels of CA125 before and after TAVI independently predict death and MACE.

Emergency and prophylactic use of miniaturized veno-arterial extracorporeal membrane oxygenation in transcatheter aortic valve implantation.

OBJECTIVES: To report our center's experience using veno-arterial extracorporeal membrane oxygenation (vaECMO) in transcatheter aortic valve implantation (TAVI). BACKGROUND: In TAVI, short-term mortality closely relates to life threatening procedural complications. VaECMO can be used to stabilize the patient in emergency situations. However, for the prophylactic use of vaECMO in very high-risk patients undergoing TAVI there is no experience. METHODS: From January 2009 to August 2011, we performed 131 TAVI. Emergency vaECMO was required in 8 cases (7%): ventricular perforation (n = 3), hemodynamic instability/cardiogenic shock (n = 4), hemodynamic deterioration due to ventricular tachycardia (n = 1). Since August 2011, during 83 procedures, prophylactic vaECMO was systematically used in very high-risk patients (n = 9, 11%) and emergency ECMO in one case (1%) due to ventricular perforation. RESULTS: Median logistic EuroScore in prophylactic vaECMO patients was considerably higher as compared to the remaining TAVI population (30% vs. 15%, P = 0.0003) while in patients with emergency vaECMO it was comparable (18% vs. 15%, P = 0.08). Comparing prophylactic to emergency vaECMO, procedural success and 30-day mortality were 100% vs. 44% (P = 0.03) and 0% vs. 44% (P = 0.02), respectively. Major vascular complications and rate of life threatening bleeding did not differ between both groups (11% vs. 11%, P = 0.99 and 11% vs. 33%, P = 0.3) and were not vaECMO-related. CONCLUSIONS: Life-threatening complications during TAVI can be managed using emergency vaECMO but mortality remains high. The use of prophylactic vaECMO in very high-risk patients is safe and may be advocated in selected cases.

Prognostic implications of stress hyperglycemia in acute ST elevation myocardial infarction. Prospective observational study.

INTRODUCTION AND OBJECTIVES: In patients with acute myocardial infarction, elevation of plasma glucose levels is associated with worse outcomes. The aim of this study was to evaluate the association between stress hyperglycemia and in-hospital mortality in patients with acute myocardial infarction with ST-segment elevation (STEMI). METHODS: We analyzed 834 consecutive patients admitted for STEMI to the Coronary Care Unit of our center. Association between admission glucose and mortality was assessed with Cox regression analysis. Discriminative accuracy of the multivariate model was assessed by Harrell's C statistic. RESULTS: Eighty-nine (10.7%) patients died during hospitalization. Optimal threshold glycemia level of 140mg/dl on admission to predict mortality was obtained by ROC curves. Those who presented glucose ≥140mg/dl showed higher rates of malignant ventricular tachyarrhythmias (28% vs. 18%, P=.001), complicative bundle branch block (5% vs. 2%, P=.005), new atrioventricular block (9% vs. 5%, P=.05) and in-hospital mortality (15% vs. 5%, P<.001). Multivariate analysis showed that those with glycemia ≥140mg/dl exhibited a 2-fold increase of in-hospital mortality risk (95% CI: 1.2-3.5, P=.008) irrespective of diabetes mellitus status (P-value for interaction=0.487 and 0.653, respectively). CONCLUSIONS: Stress hyperglycemia on admission is a predictor of mortality and arrhythmias in patients with STEMI and could be used in the stratification of risk in these patients.

Intravenous N-acetylcysteine for preventing contrast-induced nephropathy: a randomised trial.

BACKGROUND: Studies evaluating the role of N-acetylcysteine in patients undergoing coronary angiography have yielded inconsistent data. Less is known about patients with normal renal function at baseline. METHODS: Prospective, double-blind, placebo-controlled trial to determine the benefits of intravenous N-acetylcysteine as an adjunct to hydration in this kind of population. Patients were randomly assigned to receive either N-acetylcysteine (600 mg twice daily) or placebo, in addition to 0.45% intravenous saline. The primary end point was development of contrast-induced nephropathy, defined as an acute increase in the serum creatinine concentration > or = 0.5 mg/dl and/or > 25% increase above baseline level at 48 h after contrast dosing. RESULTS: A total of 216 patients were studied: N-acetylcysteine = 107 and placebo = 109. Treatment groups were similar with respect to baseline clinical characteristics. Overall incidence of contrast-induced nephropathy was 10.2%, 10.3% in the N-acetylcysteine group and 10.1% in the placebo group. Furthermore, no significant differences were observed when considering the non-diabetic population, although there was a trend towards a protective effect of N-acetylcysteine in the subgroup of 47 patients with both hypertension and diabetes. There were no significant changes in serum urea nitrogen concentrations. The incidence of in-hospital adverse clinical events was low: no patient with contrast-induced nephropathy required dialysis, the median Coronary Unit stay was 4.5 vs. 4 days, and the mortality rate was 2.8% vs. 4.6% in the N-acetylcysteine and placebo groups, respectively (p=NS). CONCLUSIONS: The prophylactic administration of intravenous N-acetylcysteine provides no additional benefit to saline hydration in high-risk coronary patients with normal renal function.

Fractional shortening-velocity ratio for assessment of aortic stenosis severity in patients with systolic dysfunction.

BACKGROUND: In the study of severity of aortic stenosis many different methods derived from transthoracic echocardiography are used. Their principal limitations are left ventricular dysfunction and calcified aortic valve. The objective of this study was to assess the utility of a described echocardiographic index: the fractional shortening-velocity ratio (FSVR=FS/4Vmax2) in those patients with left ventricular systolic dysfunction. METHODS: We studied 72 patients with aortic stenosis and aortic valvular area (AVA)< or =2 cm2. AVA was assessed by the Gorlin equation. Left ventricular systolic dysfunction was defined by FS< or =29%. Using receiver operating characteristic curves analysis to test the predictive discrimination of patients with and without critical aortic stenosis, we studied the best FSVR value to assess aortic stenosis severity. RESULTS: We found a significant linear correlation between AVA and FSVR (r=0.59; P<0.001). A value of FSVR < or =0.78 allowed the identification of patients with AVA< or =0.8 cm2 with good sensitivity and specificity (sensitivity: 94.5%; specificity: 60%; positive predictive value: 90% and negative predictive value: 75%). In our population, 22 patients (32%) showed a systolic dysfunction. The correlation AVA-FSVR was also significant in this group (r=0.68; P<0.001) and it may be even better than in the total group. However, the FSVR with the best sensitivity-specificity relation was different to the value used in the global group. A FSVR value <0.65 showed the best sensitivity-specificity relation in identifying patients with severe aortic stenosis (sensitivity: 100% and specificity: 56%). CONCLUSION: The FSVR is a very simple and noninvasive index. It allows identification of patients with severe aortic stenosis with excellent sensitivity and good specificity. It may be useful in the evaluation of patients with aortic stenosis and left ventricular dysfunction, although, there is not an accepted FSVR value with the best-combined sensitivity-specificity, to identify a critical aortic stenosis.