Sex-Related Differences in Long-Term Outcomes After Early-Onset Myocardial Infarction.

Importance: There is growing awareness of sex-related differences in cardiovascular risk profiles, but less is known about whether these extend to pre-menopausal females experiencing an early-onset myocardial infarction (MI), who may benefit from the protective effects of estrogen exposure. Methods: A nationwide study involving 125 Italian Coronary Care Units recruited 2,000 patients between 1998 and 2002 hospitalized for a type I myocardial infarction before the age of 45 years (male, n = 1,778 (88.9%). Patients were followed up for a median of 19.9 years (IQR 18.1-22.6). The primary composite endpoint was the occurrence of cardiovascular death, non-fatal myocardial re-infarction or non-fatal stroke, and the secondary endpoint of hospitalization for revascularisation by means of a percutaneous coronary intervention (PCI) or coronary artery bypass surgery (CABG). Results: ST-elevation MI was the most frequent presentation among both men and women (85.1 vs. 87.4%, p = ns), but the men had a greater baseline coronary atherosclerotic burden (median Duke Coronary Artery Disease Index: 48 vs. 23; median Syntax score 9 vs. 7; both p < 0.001). The primary composite endpoint occurred less frequently among women (25.7% vs. 37.0%; adjusted hazard ratio: 0.69, 95% CI 0.52-0.91; p = 0.01) despite being less likely to receive treatment with most secondary prevention medications during follow up. Conclusions: There are significant sex-related differences in baseline risk factors and outcomes among patients with early-onset MI: women present with a lower atherosclerotic disease burden and, although they are less frequently prescribed secondary prevention measures, experience better long-term outcomes. Trial Registration: 4272/98 Ospedale Niguarda, Ca' Granda 03/09/1998.

Long-term outcomes of early-onset myocardial infarction with non-obstructive coronary artery disease (MINOCA).

BACKGROUND: Acute myocardial infarction with non-obstructive coronary artery disease (MINOCA) is frequent in patients experiencing an early-onset MI, but data concerning its long-term prognosis are limited and conflicting. METHODS: The Italian Genetic Study on Early-onset MI enrolled 2000 patients experiencing a first MI before the age of 45 years, and had a median follow-up of 19.9 years. The composite primary endpoint was cardiovascular (CV) death, non-fatal MI, and non-fatal stroke (MACE); the secondary endpoint was rehospitalisation for coronary revascularisation. RESULTS: MINOCA occurred in 317 patients (15.9%) and, during the follow-up, there was no significant difference in MACE rates between them and the patients with obstructive coronary artery disease (MICAD: 27.8% vs 37.5%; adjusted hazard ratio [HR] 0.79, 95% confidence interval [CI] 0.57-1.09;p = 0.15). The CV death rate was lower in the MINOCA group (4.2% vs 8.4%, HR 0.26, 95%CI 0.08-0.86;p = 0.03), whereas the rates of non-fatal reinfarction (17.3% vs 25.4%; HR 0.76, 95%CI 0.52-1.13;p = 0.18), non-fatal ischemic stroke (9.5% vs 3.7%; HR 1.79, 95%CI 0.87-3.70;p = 0.12), and all-cause mortality (14.1% vs 20.7%, HR 0.73, 95%CI 0.43-1.25;p = 0.26) were not significantly different in the two groups. The rate of rehospitalisation for coronary revascularisation was lower among the MINOCA patients (6.7% vs 27.7%; HR 0.27, 95% CI 0.15-0.47;p < 0.001). CONCLUSIONS: MINOCA is frequent and not benign in patients with early-onset MI. Although there is a lower likelihood of CV death,the long-term risk of MACE and overall mortality is not significantly different from that of MICAD patients.

Comparative external validation of the PRECISE-DAPT and PARIS risk scores in 4424 acute coronary syndrome patients treated with prasugrel or ticagrelor.

BACKGROUND: The PRECISE-DAPT and PARIS risk scores (RSs) were recently developed to help clinicians at individualizing the optimal dual antiplatelet therapy duration (DAPT) after percutaneous coronary intervention (PCI). Nevertheless, external validation of these RSs it has not yet been performed in ACS (acute coronary syndrome) patients treated with prasugrel or ticagrelor in a real- world scenario. METHODS: 4424 ACS patients who underwent PCI and survived to hospital discharge, from January 2012 to December 2016 at 12 European centers, were included. PRECISE-DAPT and PARIS bleeding RS, as well as PARIS ischemic RS, were computed, and their performance at predicting major bleeding (MB; BARC type 3 or 5) and ischemic events (MI and stent thrombosis) during follow up was compared. RESULTS: After a median follow-up of 14 (interquartile range 12-20.9) months, 83 (1.88%) patients developed MB and 133 (3.0%) suffered an ischemic episode. PRECISE-DAPT performed better than PARIS bleeding RS (c-statistic = 0.653 vs. 0.593; p = .01 for comparison) in predicting MB. The RSs performance for MB prediction remained consistent in STEMI patients (c-statistic = 0.632 vs 0.575) or in those treated with prasugrel (c-statistic = 0.623 vs 0.586). PARIS ischemic RS exhibited superior discrimination in predicting ischemic complications compared to PRECISE-DAPT (c-statistic = 0.604 vs 0.568 p = .05 for comparison). CONCLUSION: Our data provide support to the use of PRECISE-DAPT in MB risk stratification for patients receiving DAPT in form of aspirin and prasugrel or ticagrelor whereas the PARIS ischemic RS has potential to complement the risk prediction with respect to ischemic events.

Management of aspirin intolerance in patients undergoing percutaneous coronary intervention. The role of mono-antiplatelet therapy: a retrospective, multicenter, study.

BACKGROUND: The optimal management of patients with aspirin intolerance undergoing stent implantation represents a challenge for physicians. The aim of this study was to assess the overall number of patients discharged with mono antiplatelet therapy after percutaneous coronary intervention (PCI). The most frequent aspirin intolerance symptoms in this population and the overall incidence of patient-oriented composite endpoints (POCE). METHODS: From January 2006 to June 2016 all patients discharged with mono-antiplatelet therapy because of aspirin intolerance/hypersensitivity/allergy and treated by means of PCI were included. Data about percutaneous treatments and aspirin intolerance were collected. POCE were evaluated at a twelve-month clinical follow-up comparing safety and efficacy of clopidogrel monotherapy versus new P2Y12 inhibitors. RESULTS: We collected 70 patients, that is 0.3% of the total amount of PCI in the considered period, 25 (35%) of them were women and the remaining 45 (65%) were men. An acute coronary syndrome (ACS) was the clinical presentation in 47 (67.1%) patients, with NSTEMI in 19 (27.1%) of them. Forty-six patients (65.7%) were treated with clopidogrel and 24 (34.3%) with new P2Y12 inhibitors. At one-year follow-up, 18 (25.7%) patients suffered a new clinically relevant adverse event, 5 (7.1%) died, 3 (4.3%) required a target vessel revascularization and 10 (14.3%) patients a target lesion revascularization. CONCLUSIONS: Our study evaluated patients with ACS or stable coronary artery disease undergoing PCI and treated with mono-antiplatelet therapy with P2Y12 inhibitors due to aspirin intolerance shows a 25% incidence of POCE at one year. Further studies with adequate sample size are required to evaluate the efficacy and safety of mono antiplatelet therapy in this clinical scenario.

Short term outcome following acute phase switch among P2Y12 inhibitors in patients presenting with acute coronary syndrome treated with PCI: A systematic review and meta-analysis including 22,500 patients from 14 studies.

INTRODUCTION: The efficacy and safety of switching P2Y12 receptor antagonists in patients admitted for acute coronary syndrome (ACS) remain unclear. We assessed the short-term clinical outcomes (in-hospital and within 30 days) of switching P2Y12 inhibitor (P2Y12I) drugs versus maintaining the same regimen by performing a comprehensive review and meta-analysis of available data. METHODS: MEDLINE/PubMed/SCOPUS/Cochrane databases were screened for studies regarding switching of P2Y12I in patients with ACS that reported 30 days follow-up. Major cardiac events (MACE) and bleeding were compared between patients who were switched/not switched. RESULTS: 22,500 patients from 14 studies were included. Unstable angina/non-ST elevation myocardial infarction (62.0%, interquartile range, 52.8%-68.0%) was the most common clinical presentation. The total number switched was 4294 (19.1%); escalation in 3416 (79.5%) patients (from clopidogrel to prasugrel, 62.9%) and de-escalation in 18.5%. Pooled analysis revealed no significant differences in MACE for any comparison; risk of bleeding was significantly increased among switched patients overall (odds ratio [OR], 1.60; 95% confidence interval [CI] 1.22-2.10) and increased in the escalation group (OR, 1.51; 95% CI, 1.06-2.16). CONCLUSIONS: Among patients presenting with ACS, switching from one P2Y12I agent to another in the acute phase seems associated with a short-term increased risk of bleeding. Accurate upfront selection and prescription of a P2Y12I based on ischemic and bleeding risks is paramount to avoid adverse events switching-related during hospitalization and in the first 30 days.

[Intravenous epinephrine for anaphylaxis: Kounis or takotsubo syndrome?] / Adrenalina endovenosa in corso di reazione anafilattica: sindrome di Kounis o takotsubo?

The presence of an acute coronary syndrome in patients with anaphylaxis is a challenging diagnostic conundrum for the cardiologist. Both Kounis syndrome and takotsubo syndrome must be taken into account. We present here the case of a 46-year-old woman suffering from ventricular fibrillation after adrenaline infusion for an anaphylactic reaction. The case report shows the important role of a clear diagnostic work-up and the role of cardiac magnetic resonance in this clinical scenario to reach the final diagnosis of reverse takotsubo cardiomyopathy.

The EUROpean and Chinese cardiac and renal Remote Ischemic Preconditioning Study (EURO-CRIPS CardioGroup I): A randomized controlled trial.

BACKGROUND: The potential protective effects of remote ischemic preconditioning (RIPC) on contrast-induced nephropathy (CIN) after percutaneous coronary intervention (PCI) remain to be defined. METHODS AND RESULTS: A double blind, randomized, placebo controlled multicenter study was performed. Patients younger than 85years old, with a renal clearance of 30-60ml/min/1.73m2, who were candidates for PCI for all clinical indications except for primary PCI, were allocated 1:1 to RIPC or to standard therapy. The primary endpoint was incidence of CIN. The secondary endpoint was incidence of peri-procedural myocardial infarction (PMI). From February 2013 to April 2014, 3108 patients who were scheduled for coronary angiography were screened for the study. 442 fulfilled the inclusion criteria and 223 received PCI. These patients were randomized to sham RIPC (n=107) or treatment group (n=116). The only pre-specified subgroup of diabetic patients included 85 (38%) cases. RIPC significantly reduced CIN incidence in the overall population (12.1% vs. 26.1%, p=0.01, with a NNT=9) and in non-diabetic patients (9.2% vs. 25.0%, p=0.02), but showed no benefit in diabetics (16.7% vs. 28.2%, p=0.21). A trend for lower PMI was seen in the intervention arm (creatine kinase - muscle brain >5 URL; 8.4% vs. 16.4%, p=0.07; troponin T >5 URL; 27% vs. 38%, p=0.21). CONCLUSIONS: Remote ischemic preconditioning significantly reduces the incidence of acute kidney injury in non-diabetic patients undergoing PCI. Larger sample size is presumably needed to assess the effect of RIPC for patients with diabetes mellitus. Clinical Trial number:NCT02195726https://www.clinicaltrial.gov/.

Impact of Chronic Total Coronary Occlusion on Recurrence of Ventricular Arrhythmias in Ischemic Secondary Prevention Implantable Cardioverter-Defibrillator Recipients (VACTO Secondary Study): Insights From Coronary Angiogram and Electrogram Analysis.

OBJECTIVES: This study sought to evaluate the incidence and clinical effect of coronary chronic total occlusions (CTOs) in patients with ischemic cardiomyopathy receiving an implantable cardioverter-defibrillator (ICD) for secondary prevention of sudden cardiac death (SCD). BACKGROUND: CTOs are common in patients with ischemic cardiomyopathy, which is the major cause of SCD. However, the impact of CTO in SCD survivors receiving an ICD is unknown. METHODS: A total of 425 patients who had survived an episode of ventricular arrhythmias and underwent ICD implantation for secondary prevention in 8 centers were included. Coronary angiogram, CTO angiographic characteristics, and ventricular arrhythmia pattern were centrally analyzed. Primary and secondary endpoints were appropriate ICD therapies and mortality during a median follow-up of 4.1 years, according to the presence of CTO in the baseline angiogram. RESULTS: Appropriate ICD therapies were higher in patients with CTO (51.7% vs. 36.3%; p = 0.001 at 4 years). Left ventricular ejection fraction (LVEF) (p = 0.015) and CTO (p = 0.001) were independent predictors of appropriate ICD therapy. Ventricular arrhythmia onset was associated to a shorter coupling interval and lower prematurity index in CTO patients. Defibrillator therapies were independently associated with worse LVEF (p = 0.046) and renal dysfunction (p = 0.023) among patients with CTO, and a tendency was observed in patients with better collateral flow (p = 0.093). Patients with poorer renal function (p = 0.029), LVEF (p = 0.041), and CTO (p = 0.033) experienced higher mortality rate. CONCLUSIONS: Among ICD recipients for secondary prevention of SCD, coronary CTO conferred a higher risk of VA recurrence and mortality in long-term follow-up. Angiographic and VA patterns could provide insights into the mechanisms of SCD and may have implications for the use of interventions designed to limit ICD shocks in this high-risk population.

Aspirin Desensitization in Patients With Coronary Artery Disease: Results of the Multicenter ADAPTED Registry (Aspirin Desensitization in Patients With Coronary Artery Disease).

BACKGROUND: There are limited data on aspirin (ASA) desensitization for patients with coronary artery disease. The aim of the present study was to assess the safety and efficacy of a standard rapid desensitization protocol in patients with ASA sensitivity undergoing coronary angiography. METHODS AND RESULTS: This is a prospective, multicenter, observational study including 7 Italian centers including patients with a history of ASA sensitivity undergoing coronary angiography with intent to undergo percutaneous coronary intervention. A total of 330 patients with history of ASA sensitivity with known/suspected stable coronary artery disease or presenting with an acute coronary syndrome, including ST-segment-elevation myocardial infarction were enrolled. Adverse effects to aspirin included urticaria (n=177, 53.6%), angioedema (n=69, 20.9%), asthma (n=65, 19.7%), and anaphylactic reaction (n=19, 5.8%). Among patients with urticaria/angioedema, 13 patients (3.9%) had a history of idiopathic chronic urticaria. All patients underwent a rapid ASA (5.5 hours) desensitization procedure. The desensitization procedure was performed before cardiac catheterization in all patients, except for those (n=78, 23.6%) presenting with ST-segment-elevation myocardial infarction who underwent the desensitization after primary percutaneous coronary intervention. Percutaneous coronary intervention was performed in 235 patients (71%) of the overall study population. The desensitization procedure was successful in 315 patients (95.4%) and in all patients with a history of anaphylactic reaction. Among the 15 patients (4.6%) who did not successfully respond to the desensitization protocol, adverse reactions were minor and responded to treatment with corticosteroids and antihistamines. Among patients with successful in-hospital ASA desensitization, 253 patients (80.3%) continued ASA for at least 12 months. Discontinuation of ASA in the 62 patients (19.7%) who had responded to the desensitization protocol was because of medical decision and not because of hypersensitivity reactions. CONCLUSIONS: A standard rapid desensitization protocol is safe and effective across a broad spectrum of patients, irrespective of the type of aspirin sensitivity manifestation, with indications to undergo coronary angiography with intent to perform percutaneous coronary intervention. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT02848339.

Efficacy and Safety of Available Protocols for Aspirin Hypersensitivity for Patients Undergoing Percutaneous Coronary Intervention: A Survey and Systematic Review.

BACKGROUND: The most suitable approach for patients with aspirin hypersensitivity undergoing percutaneous coronary intervention remains to be assessed. METHODS AND RESULTS: Pubmed, Google Scholar, and Cochrane were systematically searched for papers describing protocols about aspirin hypersensitivity in the percutaneous coronary intervention setting. Discharge from hospital with aspirin was the primary end point, whereas rates of adverse reactions being a secondary outcome. An online international survey was performed to critically analyze rates of aspirin hypersensitivity and its medical and interventional management. Eleven studies with 283 patients were included. An endovenous desensitization protocol was performed on one of them, with high efficacy rate (98%) and a low adverse reaction rate when compared with oral administration. No significant differences were reported among the oral protocols in terms of efficacy (less versus more fractionated [95.8% {95.4%-96.2%} versus 95.9% {95.2-96.5%}]), whereas higher incidence of rash and angioedema were reported for protocols with <6 doses escalation (2.6% [1.1%-4.1%] versus 2.6% [1.9%-3.2%]). In the survey, we collected answer from 86 physician of the 100 interviewed. Fifty-six percent of them managed aspirin hypersensitivity changing the therapeutic regimen (eg, clopidogrel monotherapy and indobufen). Despite the previous safety data, desensitization protocols were adopted by only 42% of surveyed cardiologist. CONCLUSIONS: Available protocols for aspirin hypersensitivity are effective and safe, representing a feasible approach for patients needing dual antiplatelet therapy.

Palliative needs for heart failure or chronic obstructive pulmonary disease: Results of a multicenter observational registry.

BACKGROUND: Heart failure (HF) and chronic obstructive pulmonary disease (COPD) share a common organ failure trajectory marked by prognostic uncertainty, which is a barrier to appropriate provision of palliative care. We describe in a prospective cohort from specialist hospital services the epidemiology and late clinical course of these chronic diseases to trace criteria for transition to palliative care in the community. METHODS AND RESULTS: Seven centers enrolled 267 patients with advanced HF (n=174) or COPD (n=93) using common (multiple hospitalizations or severely impaired functional status or cachexia) and disease-specific (HF: systolic dysfunction, NYHA classes III-IV, end-organ hypoperfusion; COPD: very severe airflow obstruction, hypoxemia, hypercapnia, or long-term oxygen therapy) entry criteria. These patients represented 7.2% and 13% respectively of the overall HF and COPD population hospitalized during one year. They showed similar symptom burden, functional and quality of life impairment, recurrent hospitalizations, and 6-month mortality (39% and 37%, respectively). Organ failure progression was the cause of death in >75%. In-hospital overall stay during the previous year was the main mortality predictor in both. Disease-specific predictors included anemia, hyponatremia, no beta-blockers in HF; older age, hypercapnia in COPD. CONCLUSIONS: Patients with advanced HF/COPD represent almost 10% of subjects hospitalized yearly with a primary diagnosis of HF or COPD, have similarly impaired functional status, disabling symptoms and reduced survival. Overall days spent in-hospital during the previous year, a "red flag" in the late clinical course of both diseases, might be used as a simple, reliable screening tool for appropriate transition to palliative care in the community.

The day when the echocardiographist went mushrooming .

We report a case of partial congenital absence of the pericardium associated with severe aortic stenosis on a bicuspid valve in a 72-year-old man. Diagnosis was based on echocardiography and confirmed with magnetic resonance imaging, and the patient benefited from pericardioplasty and aortic valve replacement.

Exercise Stress Echocardiography with Tissue Doppler Imaging (TDI) Detects Early Systolic Dysfunction in Beta-Thalassemia Major Patients without Cardiac Iron Overload.

OBJECTIVES: To evaluate left and right myocardial performance at rest and after maximal exercise by conventional and Tissue Doppler Imaging (TDI) echocardiography. BACKGROUND: Iron Overload Cardiomyopathy (IOC) is the main cause of death in thalassemia major (TM) patients but conventional Echocardiography fails to predict early cardiac dysfunction. As TDI is able to demonstrate regional myocardial dysfunction and stress test may reveal abnormalities which are not evident at rest, we wondered if echocardiographic parameters may reveal abnormalities when applied first at rest and then after a physical effort. METHODS: We enrolled 46 consecutive beta-TM patients and 39 control subjects without evidence of cardiac disease; two echocardiograms, at baseline and at the end of maximal exercise on supine bicycle ergometer, were done. All TM patients had a liver iron assessment by SQUID (Superconducting Quantum Interference Device) and a cardiac iron one by MRI (T2*) evaluation. RESULTS: 38 TM patients had no evidence of cardiac iron overload. Whereas TM patients did not shown diastolic dysfunction and all of them presented a good global response to exercise, TDI detected a reduced increase of the S' waves of left ventricle basal segment during exercise. This finding seems to have some weak but interesting relations with iron overload markers. Pulmonary artery systolic pressure (PAPs) values were greater than in control subjects both at rest and after exercise CONCLUSIONS: in our study, exercise stress TDI-echocardiography was able to demonstrate subtle systolic abnormalities that were missed by Conventional Echocardiography. Further studies are required to determine the meaning and the clinical impact of these results.

Lipid peroxidation and inflammatory molecules as markers of coronary artery disease.

Oxidized low density lipoproteins (oxLDLs) may exert several pro-inflammatory effects that can contribute to the development of coronary artery disease (CAD). Evaluating a possible correlation between oxLDLs and clinical expression of CAD, we measured specific lipid peroxidation indices in healthy subjects and in patients at different clinical stages of CAD. We observed a slight, but not significant, increase in plasma content of cholesterol oxidation products, i.e. oxysterols, in all CAD patients, and a slight, but not significant, increase of 4-hydroxynonenal-protein adducts only in subjects with acute CAD. Moreover, CAD patients showed a plasma rise of specific inflammatory proteins, i.e. C-reactive protein, intercellular adhesion molecule-1, and interleukin-8, but not of monocyte chemotactic protein-1. These preliminary data, without excluding an involvement of oxidative stress and inflammation in CAD, do not show a strict correlation between relevant plasma markers, other than C-reactive protein, and acute phase of the disease.

Prescription patterns of diuretics in chronic heart failure: a contemporary background as a clue to their role in treatment.

BACKGROUND: Diuretics are the cornerstone of treatment for the congestive symptoms of heart failure (HF). Despite their widespread use, diuretic prescription data in clinical practice are scarce. In this study we evaluated the prescription pattern of diuretics in a large population of HF outpatients, enrolled by a national network of hospital-based cardiologists. METHODS AND RESULTS: Among 11070 HF outpatients (mean age 64 +/- 12 years, 72.9% men, 29.8% New York Heart Association [NYHA] class III-IV, mean left ventricular ejection fraction [LVEF] 35+/-12%), 9247 took a diuretic, the most frequently prescribed therapeutic agent (83.5%). Loop diuretics were prescribed alone (65.5%) or combined with other diuretics in 91.6% of patients. By multivariate analysis, the strongest independent predictors of diuretic use were a previous hospital admission for HF (odds ratio [OR] 2.55, 95% confidence interval [CI] 2.28-2.86), NYHA class III-IV (OR 2.52, 95% CI 2.14-2.96), LVEF < 30% (OR 1.87, 95% CI 1.57-2.24). Aldosterone antagonists were prescribed to 2142 patients (23.1%); independent predictors of their use overlapped with those of diuretics and moreover included treatment with loop diuretics (OR 3.52, 95% CI 2.66-4.66) and digoxin (OR 1.45, 95% CI 1.29-1.64). CONCLUSIONS: In this wide series of stable HF outpatients, cardiologists prescribed diuretics in accordance with published guidelines. Evolving prescription patterns of aldosterone-receptor blockers need to be further evaluated.

Anáisis de morbimortalidad en tétanos infantil en el estado de Tamaulipas: diferencias de acuerdo al tipo de atención / Analysis of morbomortality in tetanus in infancy in the state of Tamaulipas Mexico: differencies in accordance to the type of attention

Se presentan 66 casos de tétanos infantil, manejado en dos unidades hospitalarias del estado de Tamaulipas durante un período de 5 años, en un estudio retrospectivo. Los hospitales diferían en la posibilidad de poder manejar pacientes con asistencia mecánica a la ventilación y la capacidad para proporcionar atención en unidades de cuidados intensivos. Se analizó la distribución por edades y por sexos, complicaciones presentadas y evolución en relación al manejo, que fueron diferenres, de acuerdo a los recursos de cada unidad hospitalaria. Cincuenta niños fueron recien nacidos y el resto de edades de 5.5 años (D.E. 4.2). Las complicaciones y evolución finales estuvieron determinadas más por el tipo de atención que por la patología misma: la mortalidad fue considerablemente más alta en el período neonatal, siendo la depresión respiratoria por empleo de medicamentos sedantes combinados, la causa más común de fallecimiento en este grupo atendido en un hospital que carecía de elementos para asistir mecánicamente a la ventilación. En tanto que para este mismo grupo, la causa más frecuente de muerte fue el barotrauma en la unidad hospitalaria que sí contaba con estos recursos. En niños mayores hubo muy baja mortalidad en ambos hospitales. El tétanos es una enfermedad infecciosa, curable, pero con un alto costo de atención y elevada mortalidad, principalmente en la etapa neonatal. Por ello resulta imprescindible la protección específica mediante la correcta y oportuna inmunización.