António Nunes Diogo

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.

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.

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.

Recomendações para a abordagem clínica do doente com hipertensão pulmonar

Resumen pt: A Hipertensao Pulmonar (HP) era, ate ha bem pouco tempo, uma entidade obscura, frequentemente nao identificada, porque omissa nos processos comuns de dia...

Predictors of Functional Capacity in Patients with Pulmonary Hypertension

Introduction: The 6-minute walk test (6 MWT) distance is frequently used in the prediction of pulmonary hypertension (PH) prognosis. However, potential surrogates of this measure have not been established. We aim to describe the clinical, echocardiographic, and laboratorial criteria determining the 6 MWT distance in patients with PH. Methods: In 22 consecutive PH patients, functional capacity was evaluated by the 6 MWT distance and compared with levels of neurohormonal activation biomarkers and echocardiographic parameters for right ventricular (RV) function. Results: A correlation between the 6 MWT distance and several clinical parameters was found: Borg’s pre-test classification (R=-0.46; p=0.038); WHO functional class (p=0.029). Patients with higher levels of aldosterone (R=-0.46; p=0.030), renin (R=-0.43; p=0.046) and mid-regional pro-adrenomedullin (MR-proADM, R=-0.53; p=0.009) had worse 6 MWT performance. The opposite was true for natremia levels (R=0.55; p=0.006). There was a positive correlation between the 6 MWT distance and RV global longitudinal peak systolic strain rate and early diastolic strain rate (R=0.49; p=0.038 and R=-0.55; p=0.018, respectively). On multivariate analysis, only natremia and early diastolic strain rate were predictors of the 6 MWT distance. Conclusion: The 6 MWT distance correlated with renin-angiotensin-aldosterone system activation and parameters for RV myocardial deformation. The new biomarker MR-proADM proved to be useful in the prediction of the functional capacity.

Dead Man Walking: An Extreme Case of Sinusoidal Wave Pattern in Severe Hyperkalemia

![Figure][1] A 69-year-old man presented to the emergency department with muscle weakness and low blood pressure. His medical history included diabetic nephropathy and alcoholic dilated cardiomyopathy for which he had inserted a single-chamber implantable cardiac defibrillator. The admission

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.

Adult-Onset Still's Disease and Cardiac Tamponade: A Rare Association

Adult-onset Stills 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 Stills disease rendered more difficult by pericarditis and cardiac tamponade, and they briefly review the literature on this entity.

Novel mutation in the KCNH2 gene associated with long QT syndrome

A 37-year-old man was admitted to our department after an episode of rapid regular palpitations, triggered by emotional stress. He had no previous symptoms and was not taking any medication. There was no relevant family history. The first two electrocardiograms documented sinus rhythm and a pattern of abnormal repolarization with STsegment elevation. The corrected QT interval (QTc) was between 428 and 468 ms (Figure 1A and B). Laboratory tests showed no abnormalities and exercise testing was normal. Holter monitoring documented intermittent QTc prolongation (maximum 580 ms), with no other abnormalities. Screening for mutations in the KCNQ1, KCNH2, SCN5A and KCNE1 genes for LQT1, LQT2, LQT3 and LQT5 variants of long QT syndrome (LQTS) revealed a c.529G>T (p.Glu177X) mutation in heterozygosity in the KCNH2 gene of LQT2

Copeptin for Discriminating Two-Year Mortality in Heart Failure Patients with Moderate to Severe Systolic Dysfunction

Background: Patients with heart failure and impaired systolic function may have a highly variable clinical course that renders it difficult to assess the individual prognosis. We hypothesized that ejection fraction would incompletely characterize prognosis in systolic heart failure and that biomarkers would add significant information. This study addresses the specific question whether co-peptin may add value in the evaluation of two-year prognosis in heart failure patients with known systolic dysfunction. Methods: Prospective observational cohort study in 37 patients with symptomatic chronic heart failure (classes II to IV of the NYHA classification) and moderate to severe left ventricular systolic dysfunction. We evaluated clinical, echo-cardiographic and laboratory predictors of 24-month mortality specifically assessing the role of co-peptin. Results: Six patients (16%) died during the follow-up. Patients who died had significant higher prevalence of NYHA class IV heart failure, higher blood osmolality and higher levels of NT-proBNP and co-peptin. In unvariable analysis NYHA functional class (p=0.013), serum creatinine (p=0.034), osmolality (p=0.009), NT-proBNP (p=0.013) and copeptin (p=0.003) were predictors of mortality at 24 months. Only copeptin (p=0.004) remained an independent predictor of death in Cox regression analysis. Conclusions: Our results suggest that, in patients with heart failure and impaired left ventricular systolic function, copeptin level determination may be useful for predicting mortality at two years.