Circulating miR-122-5p/miR-133b Ratio Is a Specific Early Prognostic Biomarker in Acute Myocardial Infarction.

BACKGROUND: MicroRNAs (miRNAs) are key players in cardiovascular development and disease. However, not only miRNAs of a cardiac origin have a critical role in heart function. Recent studies have demonstrated that miR-122-5p, a hepatic miRNA, increases in the bloodstream during ischemic cardiogenic shock and it is upregulated in the infarcted myocardium. The aim of the present study was to determine the potential of circulating miR-122-5p as a biomarker for early prognostic stratification of ST-segment elevation acute myocardial infarction (STEMI) patients. METHODS AND RESULTS: One hundred and forty-two consecutive STEMI patients treated with primary angioplasty were included in the study. Serum levels of miR-1-3p, -122-5p, -133a-3p, -133b, -208b-3p and -499a-5p were measured at the time of cardiac catheterization by quantitative polymerase chain reaction and related to in-hospital and long-term outcome. During a follow up of 20.8 months, 9 patients died, 6 had recurrence of myocardial infarction, and 26 patients suffered an adverse cardiovascular event. Event-free survival was significantly worse in patients with a higher miR-122-5p/133b ratio (3rd tertile distribution, above 1.42 Log(10)), having almost a 9-fold higher risk of death or myocardial infarction and a 4-fold higher risk of adverse cardiovascular events. CONCLUSIONS: This study showed that the miR-122-5p/133b ratio is a new prognostic biomarker for the early identification of STEMI patients at a higher risk of developing major adverse events after undergoing primary percutaneous coronary intervention. (Circ J 2016; 80: 2183-2191).

Adult-onset Still's disease and cardiac tamponade: a rare association.

Adult-onset Still's disease is a rare disorder with potentially severe clinical features, including cardiac involvement. This systemic inflammatory disease of unknown origin should be considered in the differential diagnosis of pericarditis, with or without pericardial effusion. Cardiac tamponade is a very rare sequela that requires an invasive approach, such as percutaneous or surgical pericardial drainage, in addition to the usual conservative therapy. The authors describe a case of adult-onset Still's disease rendered more difficult by pericarditis and cardiac tamponade, and they briefly review the literature on this entity.

An exploratory panel of biomarkers for risk prediction in pulmonary hypertension: emerging role of CT-proET-1.

BACKGROUND: Pulmonary arterial hypertension (PAH) is a rare, deadly condition. Although risk stratification is extremely important for assessment of prognosis and to guide therapy, there is lack of evidence concerning the role of novel biomarkers. In a pivotal study, we sought to comparatively investigate the predictive power of several new biomarkers in PAH. METHODS: Patients with prevalent PAH were enrolled in the study protocol, which included clinical, functional and echocardiographic assessment. Blood samples were collected at baseline for determination of NT-proBNP, CT-proET-1, MR-proANP, MR-proADM, copeptin and troponin I. Patients were clinically followed-up up to 12 months for first occurrence of hospital admission due to PAH-related clinical worsening, heart/lung transplantation or all-cause mortality. RESULTS: Among the 28 included patients the pre-specified end-point occurred in 8 (29% event rate). There were higher baseline levels of CT-proET-1, copeptin, MR-proANP, NT-proBNP and troponin I in patients who reached the composite end-point. They also had larger right atria. In multivariate Cox regression, CT-proET-1 was the only biomarker associated with increased hazard of reaching the primary composite end-point (hazard ratio per tertile increase = 10.1; 95% CI 2.0 to 50.6). CONCLUSIONS: CT-proET-1 provided prognostic information independent of other biomarkers. Importantly, we have provided the first evidence that CT-proET-1 may be superior to commonly used biomarkers.

Reduced myocardial 123-iodine metaiodobenzylguanidine uptake: a prognostic marker in familial amyloid polyneuropathy.

BACKGROUND: Transthyretin familial amyloid polyneuropathy is a hereditary form of amyloidosis characterized by sensorimotor and autonomic neuropathy, cardiac conduction defects, and infiltrative cardiomyopathy. Previous studies have suggested that myocardial sympathetic denervation assessed by 123-iodine metaiodobenzylguanidine (MIBG) imaging occurs early in disease progression. However, its prognostic significance was never evaluated. We aimed to study the long-term prognostic value of myocardial sympathetic denervation detected by MIBG imaging in transthyretin familial amyloid polyneuropathy. METHODS AND RESULTS: A total of 143 individuals with V30M transthyretin mutation underwent Holter, ambulatory blood pressure monitoring, echocardiography, and MIBG imaging. Time to all-cause death was compared with late heart-to-mediastinum MIBG uptake ratio (H/M; either in relation to the estimated lower limit of normal [1.60] or as a continuous variable) using Cox proportional hazards regression. Multivariable analyses were performed to test the prognostic accuracy of clinical, neurological, and cardiovascular parameters. During a median follow-up of 5.5 years, 32 (22%) patients died. Five-year mortality rate was 42% for late H/M <1.60 and 7% for late H/M ≥1.60 (hazard ratio, 7.19; P<0.001). Late H/M was identified as an independent prognostic predictor. Fifty-three patients were submitted to liver transplantation. In comparison with neurophysiological score-matched controls, transplanted patients had lower long-term mortality (hazard ratio, 0.32; P=0.012). Patients with late H/M<1.60 were at higher risk of unfavorable outcome but seemed to have benefited from liver transplantation. CONCLUSIONS: Cardiac sympathetic denervation as assessed by MIBG imaging is a useful prognostic marker in transthyretin familial amyloid polyneuropathy.

Sarcomeric hypertrophic cardiomyopathy: genetic profile in a Portuguese population.

BACKGROUND: Sarcomeric hypertrophic cardiomyopathy has heterogeneous phenotypic expressions, of which sudden cardiac death is the most feared. A genetic diagnosis is essential to identify subjects at risk in each family. The spectrum of disease-causing mutations in the Portuguese population is unknown. METHODS: Seventy-seven unrelated probands with hypertrophic cardiomyopathy were systematically screened for mutations by PCR and sequencing of five sarcomeric genes: MYBPC3, MYH7, TNNT2, TNNI3 and MYL2. Familial cosegregation analysis was performed in most patients. RESULTS: Thirty-four different mutations were identified in 41 (53%) index patients, 71% with familial hypertrophic cardiomyopathy. The most frequently involved gene was MYBPC3 (66%) with 22 different mutations (8 novel) in 27 patients, followed by MYH7 (22%), TNNT2 (12%) and TNNI3 (2.6%). In three patients (7%), two mutations were found in MYBPC3 and/or MYH7. Additionally, 276 relatives were screened, leading to the identification of a mean of three other affected relatives for each pedigree with the familial form of the disease. CONCLUSIONS: Disease-associated mutations were identified mostly in familial hypertrophic cardiomyopathy, corroborating the idea that rarely studied genes may be implicated in sporadic forms. Private mutations are the rule, MYBPC3 being the most commonly involved gene. Mutations in MYBPC3 and MYH7 accounted for most cases of sarcomere-related disease. Multiple mutations in these genes may occur, which highlights the importance of screening both. The detection of novel mutations strongly suggests that all coding regions should be systematically screened. Genotyping in hypertrophic cardiomyopathy enables a more precise diagnosis of the disease, with implications for risk stratification and genetic counseling.

Cystatin C as prognostic biomarker in ST-segment elevation acute myocardial infarction.

Cystatin C is a marker of renal dysfunction, and preliminary studies have suggested it might have a role as a prognostic marker in patients with coronary artery disease. The aim of the present study was to evaluate the usefulness of cystatin C for risk stratification of patients with ST-segment elevation myocardial infarction, regarding in-hospital and long-term outcomes. We included 153 consecutive patients with ST-segment elevation myocardial infarction treated by primary angioplasty. The baseline cystatin C level was measured at coronary angiography. The in-hospital outcome was determined as progression to cardiogenic shock or in-hospital death, and the long-term outcome was assessed, considering the following end points: (1) death and (2) death or reinfarction. Of the 153 patients evaluated (age 61 ± 12 years; 75.6% men), 15 (14.4%) progressed to cardiogenic shock and 4 (2.7%) died during hospitalization. The patients who progressed to cardiogenic shock or died during hospitalization had significantly greater cystatin C levels (1.02 ± 0.44 vs 0.69 ± 0.24 mg/L; p = 0.001). Long-term follow-up was available for 130 patients (583 ± 163 days). Among them, 11 patients died and 7 had reinfarction. A high baseline cystatin C level was associated with an increased risk of death (hazard ratio 8.5; p = 0.009) and death or reinfarction (hazard ratio 3.89; p = 0.021). Furthermore, only high baseline cystatin C levels and left ventricular ejection fraction ≤40% were independent predictors of the long-term risk of death, with synergistic interaction between the 2. In conclusion, cystatin C is a new biomarker with significant added prognostic value for patients with ST-segment elevation myocardial infarction undergoing primary percutaneous coronary intervention, predicting both short- and long-term outcomes.

Hybrid closure of postinfarction ventricular septal rupture enlargement after transcathether closure with Amplatzer occluder.

Ventricular septal rupture (VSR) is nowadays a rare complication of myocardial infarction (MI), but with a mortality rate still very high. Urgent surgical correction is recommended, although in specific cases percutaneous closure of a post-infarct VSR is a therapeutic option or a bridge to surgical correction. We report a case of an 80-year-old woman, with a subacute anterior MI with an antero-septal VSR. Rapid clinical deterioration in a high-surgical-risk patient led us to attempt percutaneous VSR closure at day 8 post MI. A 16-mm Amplatzer post-infarction (PI) muscular VSD closed the defect with intra-cardiac echocardiography guidance, that allowed conscious sedation. Clinical and haemodynamic improvement was immediate. Unfortunately, a small orifice distal to the device persisted, which enlarged to 8 mm over the following days, with a Qp/Qs shunt of 1.9. At day 17 post MI, the VSR was surgically closed by suturing the Amplatzer device to the septum. A residual shunt was evident, but with no progression, being the patient discharged in NYHA class I. Percutaneous closure of a post-MI VSR as a bridge to surgery is a therapeutic option in patients with high surgical risk, allowing haemodynamic stabilization and thus gaining time for a further surgical intervention if needed, improving these patients grim prognosis. Intra-cardiac echocardiography for monitoring the percutaneous procedure instead of a transoesophageal approach, as well as the surgical technique, make this case unique.

Severe rheumatic mitral stenosis: a 21st century medusa.

Although the prevalence of rheumatic fever has greatly decreased in developed countries, rheumatic mitral stenosis still causes significant morbidity and mortality. Symptomatic patients have a poor prognosis, with a 0 to 15% 10-year survival rate, particularly if percutaneous or surgical intervention are contraindicated or considered high risk. We present a case of severe rheumatic mitral stenosis with an evolution over 4 decades, in which exceptional venous distention has established.

Acute myocardial infarction complication diagnosed by three-dimensional echocardiography.

Transthoracic echocardiography is the modality of choice for the bedside diagnosis of acute myocardial infarction mechanical complications. We report the case of a ventricular septal rupture occurring soon after inferior myocardial infarction, revascularized by primary angioplasty. This challenging diagnosis was elucidated by 3D-echocardiography as 2D-imaging was not conclusive. This case demonstrates the importance of 3D-echocardiography in a cardiac intensive care setting. It provided additional information to 2D-echocardiography by identifying and locating post-acute myocardial infarction (AMI) septal rupture with implications for planning surgery.

[Guidelines for the management of pulmonary hypertension patients]. / Recomendações para a abordagem clínica do doente com hipertensão pulmonar.

INTRODUCTION: Pulmonary hypertension (PH) was until recently an obscure pathology which frequently went unidentified as it lacked a precise diagnostic strategy. Recent years have seen advances in the knowledge of the pathogenesis and mechanisms of vascular lesion of PH. This has led to the scientific community's growing interest in this area, an interest manifested in appreciable progress in the pathology's clinical characterisation, diagnostic strategies and the development of effective drugs. All of this together has been fundamental in changing the previously unfavourable prognosis of this disease. This evolution implies the need to rationalise the use of available resources through organisation of healthcare services, defining the role of each level of care, and developing norms for good clinical management practices in keeping with best medical practice guidelines. These twin aspects have attracted the interest of the scientific community, as shown by the wealth of literature, and have led healthcare authorities to introduce regulatory mechanisms. In order to improve clinical practice, the Pulmonary Vascular Disease Study Group (NEDVP) of the Portuguese Society of Internal Medicine (SPMI), the Pulmonary Hypertension Study Group (GEHTP) of the Portuguese Society of Cardiology and the boards of the Portuguese Societies of Pulmonology and Paediatric Cardiology created an interdisciplinary working group. The group's remit was to draft this document, "Guidelines for the management of pulmonary hypertension patients", based on a review of the literature and the authors' clinical expertise. These guidelines aim to present all the relevant evidence on the diagnostic and treatment strategy of PH and the definition of requirements for referral centres. The organisation of care is fundamental for an appropriate and rational use of the available resources and for the better care of the patient.

Coronary artery vasospasm and acute myocarditis: a rare association.

Coronary vasospasm is one cause of chest pain in patients with acute myocarditis. This is a rare association, with few cases reported in the literature. The authors describe a case of acute myocarditis in which presentation mimicked acute myocardial infarction. During hospitalization severe angina recurred twice, accompanied by transient ST-segment elevation in different locations. The hypothesis of coronary vasospasm is discussed. The role of cardiac magnetic resonance imaging in this context is highlighted.