Measurement of vegetations in infective endocarditis: An inaccurate method to decide the therapeutical approach.

BACKGROUND: The European Society of Cardiology and American Heart Association guidelines give a central role to the maximal vegetation diameter in the indication for surgery to prevent embolism in left sided infective endocarditis. Vegetation measuring is likely to be inaccurate. The hypothesis herein, is that the vegetation diameter is not an appropriate surgical criterion given the variability of its measurement. METHODS: Two trained echocardiographers independently measured the maximal vegetation diameter by transesophageal echocardiogram of 76 vegetations in 67 consecutive patients with definite infective endocarditis in an off-line workstation. The interobserver variability was calculated by the interclass correlation coefficient. The relationship between the strength of agreement for the cut-off points of 10 and 15 mm was also calculated. Finally, the number of patients whose surgical indication would have changed depending on which operator measured the vegetation was evaluated. RESULTS: Interobserver interclass correlation coefficient in the measurement of the maximal longitudinal diameter of the vegetations was 0.757 (0.642-0.839). The strength of agreement of the interobserver analysis for the cut-off point of 10 mm was 0.533 (0.327-0.759). For the cut-off point of 15 mm it was 0.475 (0.270-0.679). If heart failure or uncontrolled infections had been absent, the surgical indication would have changed in a total of 33 patients (33/76; 43%) depending on which operator measured the vegetation. CONCLUSIONS: The variability in the measurements of the maximal longitudinal diameter by transesophageal echocardiogram is high. Surgical indications based on the cut-off points recommended by the international guidelines should be revised.

A comparison of the clinical efficacy of echocardiography and magnetic resonance for chronic aortic regurgitation.

AIMS: Timing surgery in chronic aortic regurgitation (AR) relies mostly on echocardiography. However, cardiac magnetic resonance (CMR) may be more accurate for quantifying regurgitation and left ventricular (LV) remodelling. We aimed to compare the technical and clinical efficacies of echocardiography and CMR to account for the severity of the disease, the degree of LV remodelling, and predict AR-related outcomes. METHODS AND RESULTS: We studied 263 consecutive patients with isolated AR undergoing echocardiography and CMR. After a median follow-up of 33 months, 76 out of 197 initially asymptomatic patients reached the primary endpoint of AR-related events: 6 patients (3%) were admitted for heart failure, and 70 (36%) underwent surgery. Adjusted survival models based on CMR improved the predictions of the primary endpoint based on echocardiography: R2 = 0.37 vs. 0.22, χ2 = 97 vs. 49 (P < 0.0001), and C-index = 0.80 vs. 0.70 (P < 0.001). This resulted in a net classification index of 0.23 (0.00-0.46, P = 0.046) and an integrated discrimination improvement of 0.12 (95% confidence interval 0.08-0.58, P = 0.02). CMR-derived regurgitant fraction (<28, 28-37, or >37%) and LV end-diastolic volume (<83, 183-236, or >236 mL) adequately stratified patients with normal EF. The agreement between techniques for grading AR severity and assessing LV dilatation was poor, and CMR showed better reproducibility. CONCLUSIONS: CMR improves the clinical efficacy of ultrasound for predicting outcomes of patients with AR. This is due to its better reproducibility and accuracy for grading the severity of the disease and its impact on the LV. Regurgitant fraction, LV ejection fraction, and end-diastolic volume obtained by CMR most adequately predict AR-related events.

Long-term results after reconstruction of a new annulus in heavily calcified mitral annulus.

BACKGROUND AND AIM OF THE STUDY: In 2009 our group described a new surgical technique for patients with severe mitral valve calcification undergoing mitral valve surgery. This technique creates a new mitral annulus with plication of the mitral leaflet and the atrial wall. Our objective is to report the long-term results of the experience at our institution. MATERIALS, METHODS, AND RESULTS: From 2007 to 2016, a total of 18 patients (mean age 70.5 ± 7.8 years) underwent mitral valve replacement at our institution with this technique. One patient died on the second postoperative day. Clinical and echocardiographic in-hospital and long-term follow-up (55.5 ± 40.4 months) were performed on all the remaining 17 patients. Functional improvement was achieved in all patients. Two patients died 6 and 8 years after surgery (cancer and hemorrhagic stroke). No prosthetic dysfunction, periprosthetic leak, or annular dehiscence were detected in the long-term echocardiographic examinations. CONCLUSIONS: The reconstruction of the mitral annulus by using our technique in patients with severe calcification of the mitral annulus has low long-term mortality, good functional results, and a lack of prosthetic complications.

Effect of direct intramyocardial autologous stem cell grafting in the sub-acute phase after myocardial infarction.

BACKGROUND: To assess the efficacy and safety of intramyocardial autologous bone marrow mononuclear stem cells (BMMNC) grafting combined with coronary artery bypass grafting (CABG) on ventricular remodeling and global and regional wall motion after acute transmural myocardial infarction (AMI). METHODS: Randomized controlled trial including 20 patients with non-revascularized transmural AMI, left ventricular ejection fraction (LVEF) lower than 50% and surgical indication for CABG. The stem cell group was treated with BMMNC grafting by direct intramyocardial injection between the 10th and 15th days after AMI (subacute phase) combined with CABG under cardiopulmonary bypass; the control group was only treated with CABG. Magnetic resonance imaging with gadolinium and stress echocardiography were performed presurgery and 9 months postsurgery. RESULTS: Seventeen patients completed the follow-up. The baseline characteristics of both groups were homogeneous. No significant differences were found in the increase in LVEF (control: 6.99±4.60, cells: 7.47±6.61, P=0.876) or in the decrease in global (control: 0.28±0.39, cells: 0.22±0.28, P=0.759) or regional (control: 0.52±0.38, cells: 0.74±0.60, P=0.415) wall motion indices between the control and stem cell groups of AMI patients. No differences were found in the recovered non-viable segments (control: 1.29±1.11, cells: 2.50±1.41, P=0.091) or in the decrease in end-diastolic (control: 14.05±19.72, cells: 18.40±29.89, P=0.725) or end-systolic (control: 15.42±13.93, cells: 23.06±25.03, P=0.442) volumes. No complications from stem cell grafting were observed. CONCLUSIONS: The results from our study reported herein suggest that intramyocardial BMMNC administration during CABG in patients with AMI causes no medium- to long-term improvement in ventricular remodeling.

Efficacy of atorvastatin in prevention of atrial fibrillation after heart valve surgery in the PROFACE trial (PROphylaxis of postoperative atrial Fibrillation After Cardiac surgEry).

BACKGROUND: To evaluate the efficacy of perioperative atorvastatin administration for prophylaxis of postoperative atrial fibrillation (POAF) after heart valve surgery. METHODS: Our study included 90 patients with heart valve disease who were scheduled to undergo elective cardiac surgery. Cases with previous AF or preoperative beta-blocker therapy were excluded. Patients were randomized into the atorvastatin group, which included 47 patients who received 40 mg/day of atorvastatin 7 days before and after the surgery and the control group, which included 43 patients. Primary endpoint was the occurrence of POAF. Secondary endpoints included modifications in the preoperative and postoperative levels of the markers of inflammation (C-reactive protein [CRP]), myocardial injury (ultrasensitive troponin T and creatinine phosphokinase MB [CPK-MB]), and cardiac dysfunction (pro-brain natriuretic peptide [proBNP]) related to POAF and changes in the echocardiographic parameters, such as atrial electromechanical interval, A wave, E/A ratio, and Doppler imaging systolic velocity wave amplitude, related to POAF. RESULTS: No relationship between atorvastatin administration and reduction in the incidence of POAF was observed (42.6% in the atorvastatin vs. 30.2% in the control group) (p=0.226). No difference in the levels of CPK-MB, ultrasensitive troponin T, CRP, or proBNP and in the analyzed echocardiographic parameter was detected between both groups. CONCLUSIONS: Atorvastatin in the described dose, was not adequate for the prophylaxis of POAF after heart valve surgery. It was ineffective in controlling the inflammatory phenomena, myocardial injury, and echocardiographic predictors of POAF.

First-in-man Safety and Efficacy of the Adipose Graft Transposition Procedure (AGTP) in Patients With a Myocardial Scar.

BACKGROUND: The present study evaluates the safety and efficacy of the Adipose Graft Transposition Procedure (AGTP) as a biological regenerative innovation for patients with a chronic myocardial scar. METHODS: This prospective, randomized single-center controlled study included 10 patients with established chronic transmural myocardial scars. Candidates for myocardial revascularization were randomly allocated into two treatment groups. In the control arm (n=5), the revascularizable area was treated with CABG and the non-revascularizable area was left untouched. Patients in the AGTP-treated arm (n=5) were treated with CABG and the non-revascularizable area was covered by a biological adipose graft. The primary endpoint was the appearance of adverse effects derived from the procedure including hospital admissions and death, and 24-hour Holter monitoring arrhythmias at baseline, 1week, and 3 and 12months. Secondary endpoints of efficacy were assessed by cardiac MRI. FINDINGS: No differences in safety were observed between groups in terms of clinical or arrhythmic events. On follow-up MRI testing, participants in the AGTP-treated arm showed a borderline smaller left ventricular end systolic volume (LVESV; p=0.09) and necrosis ratio (p=0.06) at 3months but not at 12months. The AGTP-treated patient with the largest necrotic area and most dilated chambers experienced a noted improvement in necrotic mass size (-10.8%), and ventricular volumes (LVEDV: -55.2mL and LVESV: -37.8mL at one year follow-up) after inferior AGTP. INTERPRETATION: Our results indicate that AGTP is safe and may be efficacious in selected patients. Further studies are needed to assess its clinical value. (ClinicalTrials.org NCT01473433, AdiFlap Trial).

Current advances in the generation of human iPS cells: implications in cell-based regenerative medicine.

Over the last few years, the generation of induced pluripotent stem cells (iPSCs) from human somatic cells has proved to be one of the most potentially useful discoveries in regenerative medicine. iPSCs are becoming an invaluable tool to study the pathology of different diseases and for drug screening. However, several limitations still affect the possibility of applying iPS cell-based technology in therapeutic prospects. Most strategies for iPSCs generation are based on gene delivery via retroviral or lentiviral vectors, which integrate into the host's cell genome, causing a remarkable risk of insertional mutagenesis and oncogenic transformation. To avoid such risks, significant advances have been made with non-integrative reprogramming strategies. On the other hand, although many different kinds of somatic cells have been employed to generate iPSCs, there is still no consensus about the ideal type of cell to be reprogrammed. In this review we present the recent advances in the generation of human iPSCs, discussing their advantages and limitations in terms of safety and efficiency. We also present a selection of somatic cell sources, considering their capability to be reprogrammed and tissue accessibility. From a translational medicine perspective, these two topics will provide evidence to elucidate the most suitable combination of reprogramming strategy and cell source to be applied in each human iPSC-based therapy. The wide variety of diseases this technology could treat opens a hopeful future for regenerative medicine. Copyright © 2015 John Wiley & Sons, Ltd.

Symptomatic peripheral mycotic aneurysms due to infective endocarditis: a contemporary profile.

Peripheral mycotic aneurysms (PMAs) are a relatively rare but serious complication of infective endocarditis (IE). We conducted the current study to describe and compare the current epidemiologic, microbiologic, clinical, diagnostic, therapeutic, and prognostic characteristics of patients with symptomatic PMAs (SPMAs). A descriptive, comparative, retrospective observational study was performed in 3 tertiary hospitals, which are reference centers for cardiac surgery. From 922 definite IE episodes collected from 1996 to 2011, 18 patients (1.9%) had SPMAs. Because all SPMAs developed in left-sided IE, we performed a comparative study between 719 episodes of left-sided IE without SPMAs and 18 episodes with SPMAs. We found a higher frequency of intravenous drug abuse, native valve IE, intracranial bleeding, septic emboli, multiple embolisms, and IE diagnostic delay >30 days in patients with SPMAs than in patients without SPMAs. The causal microorganisms were gram-positive cocci (n =10), gram-negative bacilli (n = 2), gram-positive bacilli (n = 3), Bartonella henselae (n = 1), Candida albicans (n = 1), and negative culture (n = 1). The median IE diagnosis delay was 15 days (interquartile range [IQR], 13-33 d) in the case of high-virulence microorganisms versus 45 days (IQR, 30-240 d) in the case of low- to medium-virulence microorganisms. Twelve SPMAs were intracranial and 6 were extracranial. In 10 cases (8 intracranial and 2 extracranial), SPMAs were the initial presentation of IE; the remaining cases developed symptoms during or after finishing parenteral antibiotic treatment. The initial diagnosis of intracranial SPMAs was made by computed tomography (CT) or magnetic resonance imaging in 6 unruptured aneurysms and by angiography in 6 ruptured aneurysms. The initial test in extracranial SPMAs was Doppler ultrasonography in limbs, CT in liver, and coronary angiography in heart. Four (3 intracranial, 1 extracranial) of 7 (6 intracranial, 1 extracranial) patients treated only with antibiotics died. Surgical resection was performed in 7 (3 intracranial, 4 extracranial) and endovascular repair in 4 (3 intracranial, 1 extracranial) patients; all of them survived. In conclusion, we found that SPMAs were a rare complication of IE that developed only in left-sided IE, and especially in native valves. Intracranial hemorrhage, embolism, multiple embolisms, and diagnostic delay of IE were more common in patients with SPMAs. The microbiologic profile was diverse, but microorganisms of low-medium virulence were predominant, and had a greater delayed diagnosis of IE than those caused by microorganisms of high virulence. SPMAs were often the initial presentation of IE. The most common location of SPMAs was intracranial. Noninvasive radiologic imaging techniques were the initial imaging test in intracranial unruptured SPMAs and in most extracranial SPMAs. Surgical and endovascular treatments were safe and effective. Endovascular treatment could be the first line of treatment in selected cases. Mortality was high in those cases treated only with antibiotics.

Clinical significance of congestive heart failure in prosthetic valve endocarditis. A multicenter study with 257 patients.

INTRODUCTION AND OBJECTIVES: There have been no studies conducted in the past that focus on the significance of congestive heart failure in patients with prosthetic valve endocarditis. We studied the incidence of congestive heart failure in patients with prosthetic valve endocarditis and analyzed its profile. In this study, we addressed the prognostic significance of heart failure in patients with prosthetic valve endocarditis and analyzed its outcome based on chosen therapeutic strategies. METHODS: A total of 639 episodes of definite left-sided endocarditis were prospectively enrolled. Of them, 257 were prosthetic. Of the 257 episodes, 145 (56%) were diagnosed with heart failure. We compared the profiles of patients with prosthetic valve endocarditis based on the presence of heart failure, and performed a multivariate logistic regression model to establish the prognostic significance of heart failure in patients with prosthetic valve endocarditis and identified the prognostic factors of in-hospital mortality in these patients. RESULTS: Persistent infection (odds ratio=3.6; 95% confidence interval, 1.9-6.9) and heart failure (odds ratio=3; 95% confidence interval, 1.5-5.8) are the strongest predictive factors of in-hospital mortality in patients with prosthetic valve endocarditis. The short-term determinants of prognosis in patients with prosthetic valve endocarditis and heart failure are persistent infection (odds ratio=2.8; 95% confidence interval, 1.2-6.5), aortic involvement (odds ratio=2.5; 95% confidence interval, 1.1-5.8), abscess (odds ratio=3.6; 95% confidence interval, 1.4-9.5), diabetes mellitus (odds ratio=2.9; 95% confidence interval, 1.1-7.7), and cardiac surgery (odds ratio=0.2; 95% confidence interval, 0.1-0.5). CONCLUSIONS: The incidence of heart failure in patients with prosthetic valve endocarditis is very high. Heart failure increases the risk of in-hospital mortality by threefold in patients with prosthetic valve endocarditis. Persistent infection, aortic involvement, abscess, and diabetes mellitus are the independent risk factors associated with mortality in patients with prosthetic valve endocarditis and heart failure; however, cardiac surgery is shown to decrease mortality in these patients.

Reassessment of blood culture-negative endocarditis: its profile is similar to that of blood culture-positive endocarditis.

INTRODUCTION AND OBJECTIVES: Left-sided infective endocarditis with blood culture-negative has been associated with delayed diagnosis, a greater number of in-hospital complications and need for surgery, and consequently worse prognosis. The aim of our study was to review the current situation of culture-negative infective endocarditis. METHODS: We analyzed 749 consecutive cases of left-sided infective endocarditis, in 3 tertiary hospitals from June 1996 to 2011 and divided them into 2 groups: group I (n=106), blood culture-negative episodes, and group II (n=643) blood culture-positive episodes. We used Duke criteria for diagnosis until 2002, and its modified version by Li et al. thereafter. RESULTS: Age, sex, and comorbidity were similar in both groups. No differences were found in the proportion of patients who received antibiotic treatment before blood culture extraction between the 2 groups. The interval from symptom onset to diagnosis was similar in the 2 groups. The clinical course of both groups during hospitalization was similar. There were no differences in the development of heart failure, renal failure, or septic shock. The need for surgery (57.5% vs 55.5%; P=.697) and mortality (25.5% vs 30.6%; P=.282) were similar in the 2 groups. CONCLUSIONS: Currently, previous antibiotic therapy is no longer more prevalent in patients with blood culture-negative endocarditis. This entity does not imply a delayed diagnosis and worse prognosis compared with blood culture-positive endocarditis. In-hospital clinical course, the need for surgery and mortality are similar to those in patients with blood culture-positive endocarditis. Full English text available from:www.revespcardiol.org.

Multiple-valve infective endocarditis: clinical, microbiologic, echocardiographic, and prognostic profile.

Whether infection in more than 1 valve worsens the prognosis for endocarditis remains untested. We conducted the current study to determine the profile of multiple-valve endocarditis, compare multiple-valve endocarditis with single-valve endocarditis, and determine predictors of outcome. We conducted a prospective and observational study including 680 episodes of infective endocarditis consecutively diagnosed at 3 tertiary centers. Multiple valve involvement was present in 115 episodes (17%), and single valve involvement in 530 (78%). In the remaining 35 cases, valvular involvement could not be documented. Mean age of patients with multiple valve endocarditis was 58 years. Clinical complications were frequent (heart failure 65%, renal failure 44%, systemic embolisms 24%). The microorganism most frequently isolated was Staphylococcus aureus (22%).Factors predictive of in-hospital mortality in the univariate analysis were septic shock, prosthetic endocarditis, heart failure, and persistent infection. In the multivariate analysis, we detected heart failure (odds ratios [OR], 4.7; 95% confidence interval [CI], 1.6-13.8) and persistent infection (OR, 4.3; 95% CI, 1.7-10.8) as predictors of in-hospital mortality. Compared to single-valve endocarditis, multiple-valve disease was associated more frequently with heart failure (65% vs. 50%, p = 0.03), perivalvular complications (41% vs. 21%, p < 0.001), and heart surgery (70% vs. 54%, p = 0.002). Despite these differences, in-hospital mortality was similar (28% vs. 30%, p = 0.647). In conclusion, multiple-valve endocarditis has a poor clinical course. Mortality is similar to that of single-valve endocarditis, probably in relation with aggressive therapy including surgery in many patients. Heart failure and persistent infection are independent predictors of death.

Internal and external validation of a model to predict adverse outcomes in patients with left-sided infective endocarditis.

INTRODUCTION: Early identification of prognostic factors is essential to improve the grim prognosis associated with left-sided infective endocarditis. This group identified three independent risk factors obtained within 72 h of admission, (Staphylococcus aureus, heart failure and periannular complications) for inhospital mortality or urgent surgery in a series of 317 patients diagnosed at five tertiary centres (derivation sample). A stratification score was constructed for the test cohort by a simple arithmetic sum of the number of variables present. The goal was to validate this model internally and externally in a prospective manner with two different cohorts of patients. METHODS: The appropriateness of the model was tested prospectively on predicting events in two cohorts of patients with left-sided endocarditis: internally with the 263 consecutive patients diagnosed at the same centres where the model was derived (internal validation sample), and externally with 264 patients admitted at another hospital (external validation sample). RESULTS: The discriminatory power of the model, expressed as the area under the receiver operating characteristic curve was similar between derivation and both validation samples (internal 0.67 vs 0.68, p=0.79; external 0.67 vs p=0.74, p=0.09). There was a progressive, significant pattern of increasing event rates as the risk stratification score increased in both validation cohorts (p<0.001 by χ² for trend). CONCLUSIONS: The early risk stratification model derived, based on variables obtained within 72 h of admission, is applicable to different populations with left-sided endocarditis. A simple bedside assessment tool is provided to clinicians that identifies patients at high risk of having an adverse event.

[Long-term changes in left ventricular function following intracoronary stem cell transplantation for acute myocardial infarction]. / Evolución a largo plazo de la función ventricular tras la terapia celular intracoronaria en el infarto agudo de miocardio.

Controversy surrounds the long-term effects of intracoronary bone marrow stem cell transplantation after ST-elevation acute myocardial infarction (STEAMI). We report on the long-term changes in left ventricular function observed in 29 patients with STEAMI who were treated using this technique. Cardiac magnetic resonance imaging was performed at baseline, 6 months after transplantation, and long-term follow-up (median 27 months, interquartile range 24-35 months). The left ventricular ejection fraction had improved significantly by 6 months (from 47.6 ± 8.9% to 52.7 ± 11.6%; P = .001) and this improvement was maintained long-term, at 52.4 ± 11.8% (P = .01 vs. baseline and P = .999 vs. 6 months). There was no significant change from baseline in end-diastolic or end-systolic ventricular volume. Our findings indicate the improvement in injection fraction occurs soon after stem cell transplantation, within the first 6 months, and remains unchanged at long-term follow-up.

[Infective endocarditis in octogenarian patients]. / Endocarditis infecciosa en pacientes octogenarios.

Our aims were to investigate the clinical features and prognosis of endocarditis in octogenarian patients (aged > 79 years) and in comparison with those in younger elderly patients (aged 65-79 years) and young patients (aged < 65 years). Octogenarian subjects more frequently were male and had a community-acquired infection, mitral valve disease, and chronic anemia. Their clinical course was more insidious and benign: they presented less often with fever or new heart murmurs. When heart failure was present, it tended to be less severe. The most frequently isolated microorganisms were streptococci. The detection rate for vegetation on transesophageal echocardiography was lower in octogenarians. Octogenarians had shorter periods of hospitalization, needed surgery less frequently, and had lower mortality. Mortality in those undergoing surgery was not higher in elderly patients. Age was not an independent predictor of in-hospital mortality.